organism	gene	interpro_ids	go_term_id	go_term_label	action	is_suspect	proposed_replacement_terms	reason
9ARCH	ureC1	IPR011059	GO:0016810	hydrolase activity, acting on carbon-nitrogen (but not peptide) bonds	KEEP_AS_NON_CORE	yes		This parent C-N hydrolase term is technically consistent with urease chemistry, but GO:0009039 is the supported specific activity.
9ARCH	ureC2	IPR011059	GO:0016810	hydrolase activity, acting on carbon-nitrogen (but not peptide) bonds	KEEP_AS_NON_CORE	yes		The carbon-nitrogen hydrolase parent is compatible with the reaction, but the gene product is better represented by urease activity.
9CAUD	darB	IPR011639	GO:0006304	DNA modification	MODIFY	yes	GO:0099018 symbiont-mediated evasion of host restriction-modification system	Too general - DNA modification occurs, but the biological function is specifically antirestriction, not just general DNA modification
9CAUD	g022	IPR001098	GO:0003677	DNA binding	REMOVE	yes		Correctly identified as overly general. DNA binding is inherent in DNA polymerase activity and adds no additional functional information. The specific molecular function GO:0003887 is more informative.
9CAUD	g022	IPR002298	GO:0006261	DNA-templated DNA replication	KEEP_AS_NON_CORE	yes		Correctly identified as non-core. This term accurately describes the mechanism (DNA-templated) but lacks the viral specificity that is the key characteristic of this polymerase. Both general and specific terms are valuable in GO annotation.
9CAUD	g022		GO:0008296	3'-5'-DNA exonuclease activity	NEW	no		This is a key missing annotation. As a family A DNA polymerase, g022 is highly likely to possess 3'-5' exonuclease activity for proofreading function. This is a conserved feature of family A polymerases that improves replication fidelity by removing incorrectly incorporated nucleotides. The deep research confirms this is typical for family A enzymes.
9POAL	NCGR_LOCUS10166	IPR016161	GO:0016491	oxidoreductase activity	MARK_AS_OVER_ANNOTATED	yes		This is a very general parent term that adds no specificity beyond what GO:0004399 (histidinol dehydrogenase activity) already provides. More importantly, it is applied to a probable gene prediction artifact. The annotation is technically correct for the HDH domain but redundant and misleading in this context.
9POAL	NCGR_LOCUS10166	IPR012131	GO:0016616	oxidoreductase activity, acting on the CH-OH group of donors, NAD or NADP as acceptor	MARK_AS_OVER_ANNOTATED	yes		While technically correct for the HDH domain, this is an intermediate-specificity term that is redundant with the more specific GO:0004399 (histidinol dehydrogenase activity). Applied to a probable gene prediction artifact where annotations from two separate gene products are conflated.
9POAL	NCGR_LOCUS10166	IPR001692	GO:0046872	metal ion binding	MARK_AS_OVER_ANNOTATED	yes		This is a very general term. For the HDH domain, the more informative annotation would be zinc ion binding (GO:0008270) specifically as a catalytic cofactor. For the ARV1 domain, zinc binding relates to the structural zinc-binding motif in the AHD domain. The term is too vague and applied to a probable gene prediction artifact combining two unrelated proteins.
9POAL	NCGR_LOCUS10166	IPR012131	GO:0051287	NAD binding	MARK_AS_OVER_ANNOTATED	yes		While technically correct for the HDH domain, this annotation is applied to a probable gene prediction artifact. NAD binding is part of the histidinol dehydrogenase activity (GO:0004399) and somewhat redundant. The real HDH gene in this organism is NCGR_LOCUS4558.
9POAL	NCGR_LOCUS1270	IPR000146	GO:0016791	phosphatase activity	MARK_AS_OVER_ANNOTATED	yes		Redundant with the more specific GO:0042132. The InterPro match (IPR000146, FBPase_class-1) supports the specific FBPase activity, not just generic phosphatase activity. Retaining the general term alongside the specific one adds no information.
9POAL	NCGR_LOCUS1270	IPR020548	GO:0042578	phosphoric ester hydrolase activity	MARK_AS_OVER_ANNOTATED	yes		Redundant with GO:0042132. The active site match (IPR020548) is specifically the FBPase active site, warranting the specific term, not this general parent.
9POAL	NCGR_LOCUS1270	IPR000146,IPR020548	GO:0005975	carbohydrate metabolic process	MARK_AS_OVER_ANNOTATED	yes		Too general. The Calvin cycle annotation (GO:0019253) provides the specific biological context. This broad term adds no useful information beyond what the specific term conveys.
9POAL	NCGR_LOCUS1765	IPR003890	GO:0003723	RNA binding	KEEP_AS_NON_CORE	yes		RNA binding is accurate but very general. The more specific RNA cap binding (GO:0000339) and mRNA binding (GO:0003729) annotations already capture the relevant molecular functions more precisely.
9POAL	NCGR_LOCUS1765	IPR027159	GO:0006406	mRNA export from nucleus	ACCEPT	no		CBC plays a direct role in mRNA nuclear export. The cap and the CBC have multiple functions in mRNA biogenesis including nuclear export.
9POAL	NCGR_LOCUS1765	IPR015172,IPR015174	GO:0016070	RNA metabolic process	KEEP_AS_NON_CORE	yes		The term is accurate but uninformative. The specific processes annotated (NMD, mRNA export, RNA splicing) provide more precise functional description.
9POAL	NCGR_LOCUS1765		GO:0035196	miRNA processing	NEW	no		miRNA biogenesis is a major documented function of CBC in plants but is not captured by the existing GOA annotations. The Arabidopsis ortholog ABH1/CBP80 has been experimentally shown to be required for efficient miRNA processing.
9POAL	NCGR_LOCUS27674	IPR000850	GO:0005524	ATP binding	ACCEPT	no		ATP binding is a core requirement for UMP-CMP kinase activity. The protein contains a P-loop NTPase domain with conserved ATP binding residues identified by HAMAP and InterPro. All characterized UMP-CMP kinases require ATP as the phosphate donor [PMID:9576794].
9POAL	NCGR_LOCUS27674	IPR006266	GO:0016776	phosphotransferase activity, phosphate group as acceptor	ACCEPT	no		This is a valid parent term of the more specific UMP/CMP/dCMP kinase activities also annotated to this protein. While broader than the specific kinase activities (GO:0033862, GO:0036430, GO:0036431), it correctly captures the biochemical mechanism. The InterPro match to IPR006266 (UMP-CMP kinase family) is appropriate for the N-terminal domain.
9POAL	NCGR_LOCUS27674	IPR036298	GO:0016872	intramolecular lyase activity	REMOVE	yes		This is a doubly erroneous annotation: the intramolecular lyase activity derives from the CHI superfamily InterPro match, but the CHI-fold domain in this protein is likely a FAP subfamily member that is non-catalytic. Furthermore, the CHI-fold domain (positions 555-650) belongs to a separate gene that was incorrectly fused with the UMP-CMP kinase in this chimeric gene model. A UMP-CMP kinase has no intramolecular lyase activity.
9POAL	NCGR_LOCUS27674	IPR000850	GO:0019205	nucleobase-containing compound kinase activity	ACCEPT	no		This is a valid broader term for UMP-CMP kinase activity. The protein's N-terminal domain belongs to the adenylate kinase family UMP-CMP kinase subfamily, which phosphorylates nucleobase-containing compounds (UMP, CMP, dCMP). While less specific than GO:0033862/GO:0036430/GO:0036431, it is not incorrect.
9POAL	NCGR_LOCUS27674	IPR006266	GO:0006207	'de novo' pyrimidine nucleobase biosynthetic process	MODIFY	yes	GO:0006221 pyrimidine nucleotide biosynthetic process	UMP-CMP kinases act on pyrimidine nucleotides, not nucleobases. GO:0006207 is technically not the correct process for a nucleoside monophosphate kinase. GO:0006221 (pyrimidine nucleotide biosynthetic process) is more appropriate and already annotated.
9POAL	NCGR_LOCUS29329	IPR005106	GO:0016491	oxidoreductase activity	MARK_AS_OVER_ANNOTATED	yes		This is a true but overly general annotation. The more specific GO:0004412 (homoserine dehydrogenase activity) already captures this function precisely. Annotating both the parent and child term is redundant.
9POAL	NCGR_LOCUS29329	IPR005106	GO:0050661	NADP binding	ACCEPT	no		NADP binding is supported by the NAD(P)-binding Rossmann-fold domain and is functionally relevant to the homoserine dehydrogenase activity. The enzyme uses NADP+ as an alternative cofactor to NAD+.
9POAL	NCGR_LOCUS29329	IPR001342,IPR019811	GO:0006520	amino acid metabolic process	MARK_AS_OVER_ANNOTATED	yes		Redundant with the more specific biological process annotations. The protein is specifically involved in aspartate family amino acid biosynthesis (GO:0009067), threonine biosynthesis (GO:0009088), and homoserine biosynthesis (GO:0009090), all of which are children of this term.
9POAL	NCGR_LOCUS29329	IPR001341,IPR018042	GO:0008652	amino acid biosynthetic process	MARK_AS_OVER_ANNOTATED	yes		Redundant with GO:0009067 (aspartate family amino acid biosynthetic process), which is a more specific child term that better captures the function.
9POAL	NCGR_LOCUS67308	IPR001209,IPR018271	GO:0003735	structural constituent of ribosome	KEEP_AS_NON_CORE	yes		Correct for the RPS14 alternative splice product but not for the SDH2 product that this entry primarily represents. The InterPro match to ribosomal uS14 (IPR001209) is real and reflects the RPS14 coding region within the chimeric gene model.
9POAL	NCGR_LOCUS67308	IPR025192	GO:0009055	electron transfer activity	ACCEPT	no		This correctly captures the subunit-specific molecular function of SDH2. The iron-sulfur clusters serve as an electron relay chain within Complex II.
9POAL	NCGR_LOCUS67308	IPR004489	GO:0016491	oxidoreductase activity	KEEP_AS_NON_CORE	yes		While technically correct as a parent of electron transfer activity, this is too general to be informative. The more specific GO:0009055 is already annotated and is preferable.
9POAL	NCGR_LOCUS67308	IPR001041,IPR009051,IPR025192,IPR036010	GO:0051536	iron-sulfur cluster binding	ACCEPT	no		Core cofactor binding function of SDH2. The iron-sulfur clusters are essential for electron transfer within the respiratory chain complex.
9POAL	NCGR_LOCUS67308	IPR006058	GO:0051537	2 iron, 2 sulfur cluster binding	ACCEPT	no		SDH2 binds one [2Fe-2S] cluster as confirmed by UniProt cofactor annotation and the 2Fe-2S ferredoxin domain. This is a core cofactor binding function.
9POAL	NCGR_LOCUS67308	IPR001209,IPR018271	GO:0006412	translation	KEEP_AS_NON_CORE	yes		Correct for the RPS14 product from alternative splicing of this locus, but not for SDH2. The InterPro match to ribosomal uS14 reflects the genuine RPS14 coding region in the chimeric gene model.
9POAL	NCGR_LOCUS67308	IPR001209,IPR018271	GO:0005840	ribosome	MODIFY	yes	GO:0005763 mitochondrial small ribosomal subunit	"The generic ""ribosome"" term is too broad. The RPS14 product is specifically a component of the mitochondrial small ribosomal subunit. Additionally, this annotation applies to the RPS14 splice product, not to SDH2."
9POAL	psbA	IPR000484,IPR036854	GO:0009772	photosynthetic electron transport in photosystem II	ACCEPT	no		"This is the most appropriate biological process term for psbA/D1. The protein is the core catalytic subunit mediating electron transfer from water to plastoquinone within PSII. This term is at the right level of specificity — more informative than the broad ""photosynthesis"" term while accurately describing the specific process."
9POAL	psbA	IPR000484,IPR036854	GO:0019684	photosynthesis, light reaction	KEEP_AS_NON_CORE	yes		Accurate but partially redundant with the more specific GO:0009772 (photosynthetic electron transport in photosystem II), which is already annotated. This broader term adds little additional information beyond what the PSII-specific electron transport term captures. Not wrong, but not the most informative annotation.
ACEPA	xdhB	IPR016208	GO:0005506	iron ion binding	ACCEPT	no		XdhB contains [2Fe-2S] iron-sulfur clusters essential for electron transfer from the Mo center to FAD/NAD+. This annotation is accurate based on conserved domain analysis.
ACEPA	xdhB	IPR014309	GO:0030151	molybdenum ion binding	ACCEPT	no		XdhB harbors the molybdopterin cofactor essential for catalysis. The Mo center is required for substrate oxidation at the active site.
ACET2	P10477	IPR018087	GO:0005975	carbohydrate metabolic process	KEEP_AS_NON_CORE	yes		While technically correct, this is a very high-level term. The more specific terms (cellulose catabolic process, xylan catabolic process, glucomannan catabolic process) provide much better functional annotation.
ACET2	P10477	IPR001087	GO:0016788	hydrolase activity, acting on ester bonds	ACCEPT	no		This correctly captures the esterase activity of the CE2 domain. The enzyme hydrolyzes acetyl ester bonds in acetylated polysaccharides. More specific terms (acetylxylan esterase activity) provide additional detail.
ACET2	P10477	IPR037461	GO:0052689	carboxylic ester hydrolase activity	ACCEPT	no		This is an accurate parent term for the esterase activity. The CE2 domain catalyzes hydrolysis of acetyl ester bonds, releasing acetate from polysaccharide substrates.
ACET2	P10478	IPR001000,IPR002105,IPR044846	GO:0004553	hydrolase activity, hydrolyzing O-glycosyl compounds	ACCEPT	no		This is a valid parent term annotation based on InterPro domain prediction. While more specific terms exist (GO:0031176), hierarchical IEA annotations to parent terms are acceptable as they correctly capture the enzyme class. The GH10 domain does indeed hydrolyze O-glycosyl compounds (beta-1,4-xylosidic linkages in xylan).
ACET2	P10478	IPR001000,IPR044846	GO:0005975	carbohydrate metabolic process	MARK_AS_OVER_ANNOTATED	yes		While XynZ participates in carbohydrate metabolism, this term is too general. The protein is specifically involved in xylan catabolic process (GO:0045493), which is already annotated. This high-level IEA annotation does not add meaningful functional information and could be misleading about the specificity of the enzyme's role.
ACET2	P10478	IPR005084,IPR006584	GO:0030246	carbohydrate binding	MODIFY	yes	GO:2001062 xylan binding	While the annotation is directionally correct (XynZ does bind carbohydrates), the CBM6 domain in XynZ specifically binds xylan substrates to facilitate enzymatic activity. A more appropriate term would be GO:2001062 (xylan binding), which specifically describes binding to xylan polymers. The CBM6 domain in C. thermocellum xylanases is known to target xylan, enhancing the enzyme's effectiveness on this substrate.
ACET2	P10478		GO:0030600	feruloyl esterase activity	NEW	no	GO:0030600 feruloyl esterase activity	The CE1 domain of XynZ provides feruloyl esterase activity, which is a documented accessory function of this enzyme. UniProt cross-references ESTHER database (clotm-xynz; A85-Feruloyl-Esterase) and BRENDA entry for EC 3.1.1.73 (feruloyl esterase). This is a core function of the protein that should be annotated.
ACET2	P15329	IPR002105	GO:0004553	hydrolase activity, hydrolyzing O-glycosyl compounds	REMOVE	yes		The SGNH hydrolase domain (Pfam: Lipase_GDSL_2, InterPro: IPR013830) present in CelX is characteristic of serine esterases, not glycoside hydrolases. SGNH hydrolases catalyze ester bond cleavage using a Ser-His-Asp catalytic triad, while glycoside hydrolases use different mechanisms (retaining/inverting) and have distinct catalytic residues. The annotation is based on the dockerin domain which only indicates cellulosome association, not enzymatic activity. The original publication (PMID:3066698) does not provide experimental evidence for glycoside hydrolase activity of CelX.
ACET2	P38535	IPR001000,IPR010502,IPR018087,IPR044846	GO:0004553	hydrolase activity, hydrolyzing O-glycosyl compounds	ACCEPT	no		This is a valid parent term for xylanase activity. The GH10 catalytic domain of XynX hydrolyzes O-glycosyl bonds (specifically beta-1,4-xylosidic linkages). While more specific terms exist, this IEA annotation from InterPro domain mapping (GH10, CBM9, CBM22) is technically correct as a general classification. It appropriately captures the broad enzymatic mechanism.
ACET2	P38535	IPR001000,IPR018087,IPR044846	GO:0005975	carbohydrate metabolic process	KEEP_AS_NON_CORE	yes		While technically correct (xylan is a carbohydrate and XynX contributes to its metabolism), this term is extremely broad and provides little specific information about XynX's function. More informative terms like xylan catabolic process (GO:0045493) better describe the enzyme's role. This annotation is retained as a non-core function since it represents an IEA from InterPro domain mapping that accurately but non-specifically captures XynX's involvement in carbohydrate processing.
ACET2	P38535	IPR010502	GO:0016052	carbohydrate catabolic process	KEEP_AS_NON_CORE	yes		This term correctly indicates that XynX is involved in breaking down carbohydrates. However, it is too general - XynX specifically catalyzes xylan catabolism, not general carbohydrate catabolism. The InterPro-based annotation from CBM9 domain (IPR010502) correctly identifies involvement in carbohydrate degradation. The more specific term xylan catabolic process (GO:0045493) would better capture the enzyme's function, but this annotation remains valid as a parent term.
ACET2	P38535	IPR010502	GO:0030246	carbohydrate binding	MODIFY	yes	GO:2001062 xylan binding	"While XynX does bind carbohydrates via its CBM domains, the term ""carbohydrate binding"" is too general. XynX specifically binds xylan through its thermostabilizing domain (TSD, which is a CBM22 xylan-binding domain) and CBM9 domains. The CBM9 domains in XynX have been shown to bind xylan and lichenan. A more informative annotation would be xylan binding (GO:2001062), which accurately reflects the substrate specificity of XynX's binding modules."
ACET2	P51584	IPR001000,IPR002105,IPR044846	GO:0004553	hydrolase activity, hydrolyzing O-glycosyl compounds	ACCEPT	no		This is a correct parent term for endo-1,4-beta-xylanase activity. While not as informative as the more specific term GO:0031176, retaining parent terms in IEA annotations is acceptable as they capture the broader enzymatic class.
ACET2	P51584	IPR001000,IPR044846	GO:0005975	carbohydrate metabolic process	ACCEPT	no		This is a correct but very general parent term. The annotation accurately captures that XynY is involved in carbohydrate metabolism (specifically catabolism of xylan). IEA mappings to broad parent terms are acceptable alongside more specific annotations.
ACET2	P71143	IPR002102	GO:0000272	polysaccharide catabolic process	REMOVE	yes		SdbA contains a type II cohesin domain that binds dockerin, not carbohydrates or polysaccharides. The protein has no enzymatic activity whatsoever. It functions solely as a structural adaptor to tether cellulosomes to the cell surface via SLH-mediated cell envelope binding. The annotation derives from an incorrect InterPro2GO mapping that conflates structural similarity between cohesin and CBM domains with functional similarity.
ACET2	P71143	IPR002102,IPR008965	GO:0030246	carbohydrate binding	MODIFY	yes	GO:1990309 type-II dockerin domain binding	SdbA cohesin domain specifically binds the dockerin domain of CipA scaffoldin - this is a well-characterized protein-protein interaction, not carbohydrate binding. The structural similarity between cohesin domains and CBM domains (both belong to beta-sandwich fold families) has led to erroneous functional annotation. The correct molecular function is type-II dockerin domain binding, which accurately describes SdbA role in capturing CipA for cell surface anchoring.
ACET2	Q01866	IPR002105	GO:0004553	hydrolase activity, hydrolyzing O-glycosyl compounds	REMOVE	yes		CipB is a non-catalytic scaffoldin protein. The IEA annotation from InterPro IPR002105 (Dockerin_1_rpt) incorrectly associates dockerin domains with hydrolase activity. Dockerin domains are protein-protein interaction modules that bind cohesin domains, enabling assembly of the cellulosome complex. CipB contains no glycosyl hydrolase catalytic domains. This is a clear case of over-annotation from automated pipelines that conflate domain presence with catalytic function.
ACET2	Q01866	IPR001956,IPR036966	GO:0005975	carbohydrate metabolic process	MODIFY	yes	GO:0044575 cellulosome assembly	The annotation is too broad and implies direct metabolic activity. CipB's role is structural/organizational - it assembles and organizes catalytic enzymes that perform carbohydrate metabolism. The protein's function is better captured by cellulosome assembly.
ACET2	Q01866	IPR002102,IPR008965	GO:0030246	carbohydrate binding	KEEP_AS_NON_CORE	yes		While technically correct due to the CBM3 domain, this is redundant with the more specific cellulose binding annotation (GO:0030248). The CBM3 domain specifically binds cellulose, not carbohydrates in general. Keeping as non-core since it is not incorrect but is less informative than the specific term.
ACET2	Q01866	IPR001956,IPR036966	GO:0030248	cellulose binding	ACCEPT	no		CipB unambiguously contains a CBM3 domain that confers cellulose binding activity. This is a core molecular function of the scaffoldin protein.
ACET2	Q84C00	IPR002105,IPR016134,IPR036439	GO:0000272	polysaccharide catabolic process	MODIFY	yes	GO:0051275 beta-glucan catabolic process	The term 'polysaccharide catabolic process' is overly broad. LicB is a lichenase that specifically hydrolyzes beta-glucans containing (1->3) and (1->4) linkages. UniProt confirms the catalytic activity with EC 3.2.1.73. A more specific biological process term should be used.
ACET2	Q84C00	IPR000757,IPR002105,IPR008263,IPR008264,IPR044791	GO:0004553	hydrolase activity, hydrolyzing O-glycosyl compounds	ACCEPT	no		While this is a general parent term, it is not incorrect for LicB. The enzyme hydrolyzes O-glycosyl bonds in beta-glucans. Since the more specific 'licheninase activity' (GO:0042972) is also annotated, this broader term provides hierarchical context and is acceptable to retain.
ACET2	Q84C00	IPR000757,IPR008263,IPR008264	GO:0005975	carbohydrate metabolic process	MODIFY	yes	GO:0051275 beta-glucan catabolic process	'Carbohydrate metabolic process' is the grandparent term for nearly all sugar-related processes. For a specific enzyme like lichenase, a more informative term such as 'beta-glucan catabolic process' (GO:0051275) should be used to accurately reflect the enzyme's biological role.
ACET2	ancA	IPR002102,IPR008965	GO:0030246	carbohydrate binding	MODIFY	yes	GO:1990309 type-II dockerin domain binding	The term carbohydrate binding is too general and misleading for ancAs primary function. AncA specifically binds to dockerin domains of scaffoldins (particularly CipAs dockerin) via its Type II cohesin domain. While SLH domains may interact with cell wall carbohydrates, the core molecular function is dockerin binding, not general carbohydrate binding.
ACET2	celA	IPR002037,IPR008928,IPR012341	GO:0005975	carbohydrate metabolic process	ACCEPT	no		This annotation is correct but very broad. It is inferred from InterPro records IPR002037 (Glyco_hydro_8), IPR008928 (6-hairpin_glycosidase_sf), and IPR012341 (6hp_glycosidase-like_sf). While the more specific GO:0030245 (cellulose catabolic process) better captures CelA's function, this broader term is not incorrect and acceptable for an IEA annotation derived from domain membership.
ACET2	celC	IPR001547,IPR018087	GO:0004553	hydrolase activity, hydrolyzing O-glycosyl compounds	ACCEPT	no		As a GH5 family endoglucanase, CelC hydrolyzes O-glycosyl compounds (specifically beta-1,4-glucosidic bonds). The InterPro-based IEA annotation is accurate. This parent term is retained alongside the more specific cellulase activity term.
ACET2	celC	IPR018087	GO:0005975	carbohydrate metabolic process	ACCEPT	no		While very general, this annotation is not incorrect. CelC is involved in carbohydrate metabolism via its cellulolytic activity. More specific child terms (cellulose catabolic process) provide better functional resolution. IEA from InterPro is reasonable for this broad term.
ACET2	celD	IPR001701,IPR004197,IPR008928,IPR012341	GO:0005975	carbohydrate metabolic process	MARK_AS_OVER_ANNOTATED	yes		GO:0005975 'carbohydrate metabolic process' is a very high-level term that encompasses essentially all carbohydrate metabolism. CelD functions specifically in cellulose degradation as evidenced by its UniProt keywords (Cellulose degradation, Glycosidase) and EC classification (3.2.1.4). The GO:0030245 'cellulose catabolic process' annotation already present is far more informative and specific.
ACET2	celK	IPR001701,IPR004197,IPR008928,IPR012341	GO:0005975	carbohydrate metabolic process	ACCEPT	no		This is a very high-level biological process term that is technically accurate but provides minimal information. Since more specific BP annotations exist (GO:0030245 cellulose catabolic process), this broad term is acceptable as hierarchical context but not informative as a standalone annotation. IEA from InterPro is appropriate for this level of granularity.
ACET2	celK	IPR004197	GO:0008810	cellulase activity	MODIFY	yes	GO:0016162 cellulose 1,4-beta-cellobiosidase activity	"GO:0008810 (cellulase activity) is defined as ""catalysis of the endohydrolysis of (1->4)-beta-D-glucosidic linkages in cellulose"". CelK is classified as EC 3.2.1.91 (cellulose 1,4-beta-cellobiosidase), which is an exo-acting enzyme that releases cellobiose from the non-reducing ends. The correct annotation is GO:0016162 (cellulose 1,4-beta-cellobiosidase activity), which is already present in the annotation set."
ACET2	celS	IPR008928,IPR012341	GO:0005975	carbohydrate metabolic process	MARK_AS_OVER_ANNOTATED	yes		This term is too general. More specific biological process terms are already annotated (GO:0030245, cellulose catabolic process). The annotation from InterPro superfamily domains (IPR008928, IPR012341) provides only general functional inference. Retaining this alongside the more specific cellulose catabolic process term is redundant.
ACET2	celS	IPR000556	GO:0008810	cellulase activity	ACCEPT	no		This is a valid parent term for CelS activity. The enzyme is classified as a cellulase, specifically a cellobiohydrolase. The annotation from InterPro (IPR000556, Glycoside hydrolase family 48) is appropriate. While GO:0102252 provides more specificity about the reducing-end preference, cellulase activity is not incorrect and represents a legitimate intermediate term in the hierarchy.
ACET2	cipA	IPR002105	GO:0004553	hydrolase activity, hydrolyzing O-glycosyl compounds	REMOVE	yes		CipA is explicitly described in the literature as a non-catalytic scaffolding glycoprotein (UniProt CC-FUNCTION). The UniProt function annotation states that CipA acts as a scaffolding protein in the cellulosome and promotes binding of cellulose to the catalytic domains of the cellulolytic enzymes - note it promotes binding TO catalytic domains, it does not have catalytic activity itself. The deep research confirms CipA is a non-catalytic structural organizer (cipA-deep-research-falcon.md). The InterPro domain IPR002105 (Dockerin_1_rpt) is present in both scaffoldins and catalytic enzymes; the hydrolase activity annotation was incorrectly transferred because dockerins are commonly found in hydrolases, but the scaffoldin CipA only uses its dockerin (type II) for anchoring to cell-surface proteins, not for catalysis. This is a clear over-annotation error.
ACET2	cipA	IPR001956,IPR036966	GO:0005975	carbohydrate metabolic process	MODIFY	yes	GO:0044575 cellulosome assembly	CipA's CBM3a domain binds cellulose but does not metabolize it. The protein's role is structural - organizing the cellulosome for efficient carbohydrate degradation. A more appropriate annotation would be GO:0044575 (cellulosome assembly) which captures the actual biological process CipA participates in. The annotation to carbohydrate metabolic process incorrectly implies direct metabolic activity.
ACET2	cipA	IPR002102,IPR008965	GO:0030246	carbohydrate binding	ACCEPT	no		CipA contains a well-characterized CBM3a (carbohydrate-binding module family 3a) domain at positions 365-523. The deep research confirms that CBM3a targets crystalline cellulose to increase local enzyme concentration and synergize hydrolysis. CBM3a is the prevalent cellulosomal CBM in C. thermocellum (cipA-deep-research-falcon.md). The crystal structure of this domain has been solved (PDB: 1NBC at 1.75 A resolution). This is a core molecular function.
ACET2	cipA	IPR001956,IPR036966	GO:0030248	cellulose binding	ACCEPT	no		CipA's CBM3a domain (residues 365-523) specifically binds crystalline cellulose, targeting the cellulosome to its substrate. This is experimentally verified through structural studies - the crystal structure of the CBM3a domain was solved at 1.75 A resolution (PDB: 1NBC; Tormo et al., EMBO J 1996). The deep research states that CBM3a function targets crystalline cellulose to increase local enzyme concentration and synergize hydrolysis (cipA-deep-research-falcon.md). This is a core function of CipA - without cellulose binding, the cellulosome cannot target its substrate.
ACIBA	blaOXA-400	IPR001460	GO:0008658	penicillin binding	MODIFY	yes	GO:0008800 beta-lactamase activity	Replace the broad or over-specific electronic term 'penicillin binding' with beta-lactamase activity based on UniProt/CARD determinant identity and the curated ARO->GO mapping.
ACIBA	blaOXA-480	IPR001460	GO:0008658	penicillin binding	MODIFY	yes	GO:0008800 beta-lactamase activity	Replace the broad or over-specific electronic term 'penicillin binding' with beta-lactamase activity based on UniProt/CARD determinant identity and the curated ARO->GO mapping.
ACIBZ	blaOXA-418	IPR001460	GO:0008658	penicillin binding	MODIFY	yes	GO:0008800 beta-lactamase activity	Replace the broad or over-specific electronic term 'penicillin binding' with beta-lactamase activity based on UniProt/CARD determinant identity and the curated ARO->GO mapping.
AEDAE	A0A6I8TLE4		GO:0005096	GTPase activator activity	NEW	no		Strong domain-based evidence from multiple independent sources (InterPro, CDD, PANTHER, PROSITE, Pfam) all converge on RasGAP function. The RasGAP domain is well-characterized with high predictive value for GTPase activator activity.
AEDAE	A0A6I8TLE4		GO:0007265	Ras protein signal transduction	NEW	no		RasGAP domain-containing proteins are by definition participants in Ras protein signal transduction. This is the direct process annotation corresponding to the molecular function.
AEDAE	A0A6I8TLE4		GO:0046580	negative regulation of Ras protein signal transduction	NEW	no		The GAP mechanism is inherently inhibitory toward Ras signaling. All characterized RasGAP domain proteins function as negative regulators.
AEDAE	A0A6I8TLE4		GO:0005829	cytosol	NEW	no		Cytosol is the default localization for soluble RasGAP proteins before membrane recruitment. Supported by domain architecture inference from the deep research report.
AEDAE	A0A6I8TLE4		GO:0005886	plasma membrane	NEW	no		C2 and PH domains are well-established membrane-targeting modules. RasGAP function requires co-localization with membrane-anchored Ras GTPases at the plasma membrane.
AERER	ermA	IPR020596,IPR020598	GO:0000154	rRNA modification	ACCEPT	no		Erm enzymes confer resistance by methylating 23S rRNA; this process annotation is biologically appropriate.
AERME	mcr-3	IPR012549	GO:0016020	membrane	MODIFY	yes	GO:0005886 plasma membrane	Use plasma membrane rather than the generic membrane term where possible.
AERME	mcr-3	IPR040423	GO:0016772	transferase activity, transferring phosphorus-containing groups	MODIFY	yes	GO:0043838 phosphatidylethanolamine:Kdo2-lipid A phosphoethanolamine transferase activity	Replace the broad or over-specific electronic term 'transferase activity, transferring phosphorus-containing groups' with phosphatidylethanolamine:Kdo2-lipid A phosphoethanolamine transferase activity based on UniProt/CARD determinant identity and the curated ARO->GO mapping.
AILME	A0A7N5KEZ3_AILME	IPR002494	GO:0045095	keratin filament	ACCEPT	no		The protein is a high-sulfur (B2) keratin-associated protein (Pfam PF13885, InterPro IPR002494) whose biological role is structural cross-linking of keratin intermediate filaments into the hard-keratin matrix [PMID:29797269]. Keratin filament is the appropriate, conventional cellular-component term for KAPs (cross-checked against human KRTAP4-3, UniProtKB:Q9BYR4, which carries the identical InterPro keratin-filament annotation). This is the most informative existing annotation and reflects the core localization, though no panda-specific experimental data exist.
ANOGA	7DL3	IPR006170,IPR036728	GO:0005549	odorant binding	REMOVE	yes		"D7L3 is a salivary protein that functions as a serotonin kratagonist, not an odorant-binding protein. The PBP/GOBP fold has been evolutionarily repurposed in D7 proteins for binding biogenic amines and eicosanoids in saliva. D7L3 is expressed in adult female salivary glands [UniProt A0A1S4HE90], not olfactory tissues. The actual molecular function is serotonin binding (GO:0051378). Serotonin (5-hydroxytryptamine) is a neurotransmitter/vasoactive amine, not an odorant. PMID:35460690 explicitly shows ""AngaD7L3 binds serotonin"" via isothermal titration calorimetry. This is a clear case where structural family membership does not predict function."
ANOGA	CLIPB4	IPR001254,IPR018114	GO:0004252	serine-type endopeptidase activity	ACCEPT	no		This is the core molecular function of CLIPB4 and is strongly supported. UniProt annotates EC=3.4.21.- based on experimental evidence (PMID:37703846). The protein has the complete catalytic triad (His153, Asp213, Ser311) and experimentally demonstrated protease activity cleaving CLIPB8 and CLIPA8. The term is appropriately specific for the enzymatic activity.
ANOGA	D7L1	IPR006170,IPR036728	GO:0005549	odorant binding	MODIFY	yes	GO:0050542 icosanoid binding	"D7L1 belongs to the PBP/GOBP structural family (InterPro IPR006170), which led to this IEA annotation. However, the D7 long-form proteins have evolutionarily repurposed this fold for binding eicosanoids in saliva, not odorants in antennae. D7L1 is expressed exclusively in female salivary glands, not olfactory tissues. The actual molecular function is icosanoid binding (GO:0050542) - specifically binding leukotriene C4 and thromboxane A2 analog U-46619 [PMID:35460690]. IMPORTANTLY: D7L1 does NOT bind biogenic amines (serotonin, histamine) - this is the key difference from short-form D7 proteins like D7r1. The GO:0005549 definition ""Binding to an odorant, any substance capable of stimulating the sense of smell"" does not apply - leukotriene C4 and thromboxane A2 are not odorants. UniProt explicitly states ""Binds leukotriene C4 and U-46619, a stable analog of thromboxane A2"" [PMID:35460690]."
ANOGA	D7L2	IPR006170,IPR036728	GO:0005549	odorant binding	REMOVE	yes		"D7L2 belongs to the PBP/GOBP structural family (InterPro IPR006170), which led to this IEA annotation via GO_REF:0000002. However, D7 proteins have evolutionarily repurposed this fold for binding host hemostatic/inflammatory mediators in saliva, not odorants in antennae. D7L2 is secreted from female salivary glands during blood feeding [UniProt A0A1S4GYJ6]. The actual molecular functions involve binding coagulation factors XII and XI [PMID:35460690, UniProt A0A1S4GYJ6] and weakly binding leukotrienes B4 and D4 [PMID:35460690, UniProt A0A1S4GYJ6]. The GO:0005549 definition ""Binding to an odorant, any substance capable of stimulating the sense of smell"" is completely inappropriate - coagulation factors and leukotrienes are not odorants. This is a clear case where structural homology does not predict function. Deep research on the D7 family confirms long-form D7s ""bind lipid mediators (cysteinyl leukotrienes; some bind thromboxane A2 analogs) via their N-terminal domain"" [file:ANOGA/D7r1/D7r1-deep-research-falcon.md], not odorants."
ANOGA	D7r1	IPR006170,IPR036728	GO:0005549	odorant binding	MODIFY	yes	GO:0051378 serotonin binding; GO:0051381 histamine binding	"D7r1 belongs to the PBP/GOBP structural family (InterPro IPR006170), which led to this IEA annotation. However, the D7 proteins have evolutionarily repurposed this fold for binding biogenic amines in saliva, not odorants in antennae. D7r1 is expressed exclusively in female salivary glands [PMID:9990055, PMID:11841502], not olfactory tissues. The actual molecular function is serotonin binding (GO:0051378) and histamine binding (GO:0051381). This is a clear case where structural homology does not predict function. The GO:0005549 definition ""Binding to an odorant, any substance capable of stimulating the sense of smell"" does not apply - serotonin and histamine are not odorants. Deep research confirms ""short-form D7s (including D7r1) predominantly bind biogenic amines (serotonin/5-HT, histamine, epinephrine/norepinephrine)"" [file:ANOGA/D7r1/D7r1-deep-research-falcon.md]."
ANOGA	D7r2	IPR006170,IPR036728	GO:0005549	odorant binding	MODIFY	yes	GO:0051378 serotonin binding; GO:0051381 histamine binding; GO:0051380 norepinephrine binding	"D7r2 belongs to the PBP/GOBP structural family (InterPro IPR006170), which led to this IEA annotation via GO_REF:0000002. However, the D7 proteins have evolutionarily repurposed this fold for binding biogenic amines in saliva, not odorants in antennae. D7r2 is expressed exclusively in female salivary glands [PMID:11841502, PMID:9990055], not olfactory tissues. The actual molecular function is binding serotonin (GO:0051378), histamine (GO:0051381), and norepinephrine (GO:0051380). UniProt confirms ""Binds serotonin, noradrenaline, histamine and adrenaline (PubMed:16301315)"" [UniProt Q9UB31]. This is a clear case where structural homology does not predict function. The GO:0005549 definition ""Binding to an odorant, any substance capable of stimulating the sense of smell"" does not apply - serotonin, histamine, and norepinephrine are not odorants. Deep research confirms D7 short forms ""bind serotonin, histamine, and catecholamines with high affinity"" [file:ANOGA/D7r1/D7r1-deep-research-falcon.md]."
ANOGA	D7r3	IPR006170,IPR036728	GO:0005549	odorant binding	MODIFY	yes	GO:0051378 serotonin binding; GO:0051381 histamine binding	"D7r3 belongs to the PBP/GOBP structural family (InterPro IPR006170), which led to this IEA annotation. However, the D7 proteins have evolutionarily repurposed this fold for binding biogenic amines in saliva, not odorants in antennae. D7r3 is expressed exclusively in female salivary glands [PMID:11841502, PMID:9990055], not olfactory tissues. UniProt explicitly states ""Binds serotonin, noradrenaline, histamine and adrenaline"" [UniProt:A0A1S4GYH9, PMID:16301315]. The actual molecular functions are serotonin binding (GO:0051378) and histamine binding (GO:0051381). This is a clear case where structural homology does not predict function. The GO:0005549 definition ""Binding to an odorant, any substance capable of stimulating the sense of smell"" does not apply - serotonin and histamine are not odorants. Deep research on D7 family confirms ""short-form D7s (including D7r1) predominantly bind biogenic amines (serotonin/5-HT, histamine, epinephrine/norepinephrine)"" [file:ANOGA/D7r1/D7r1-deep-research-falcon.md]."
ANOGA	D7r4	IPR006170,IPR036728	GO:0005549	odorant binding	MODIFY	yes	GO:0051378 serotonin binding; GO:0051381 histamine binding; GO:0051380 norepinephrine binding	"D7r4 belongs to the PBP/GOBP structural family (InterPro IPR006170), which led to this IEA annotation. However, the D7 proteins have evolutionarily repurposed this fold for binding biogenic amines in saliva, not odorants in antennae. D7r4 is expressed exclusively in female salivary glands [PMID:12062411], not olfactory tissues. The actual molecular functions are serotonin binding (GO:0051378), histamine binding (GO:0051381), norepinephrine binding (GO:0051380), and tryptamine binding. Crystal structures of D7r4 with bound serotonin (PDB:2QEH), histamine (PDB:2QEB), norepinephrine (PDB:2QEO), and tryptamine (PDB:2PQL) demonstrate the actual binding specificity [PMID:17928288]. UniProt documents specific binding residues for each ligand. The GO:0005549 definition ""Binding to an odorant, any substance capable of stimulating the sense of smell"" does not apply - serotonin, histamine, norepinephrine, and tryptamine are not odorants. Deep research confirms short-form D7s ""predominantly bind biogenic amines (serotonin/5-HT, histamine, epinephrine/norepinephrine)"" [file:ANOGA/D7r1/D7r1-deep-research-falcon.md]."
ANOGA	D7r5	IPR006170,IPR036728	GO:0005549	odorant binding	REMOVE	yes		"This is a clear over-annotation based on domain homology that contradicts experimental evidence. The original study (PMID:16301315) specifically tested binding using isothermal microcalorimetry and chromatographic methods, finding that ""four of these five short D7 proteins...bind serotonin with high affinity, as well as histamine and norepinephrine. The nonbinding D7 protein [D7r5] is poorly expressed in the salivary glands and appears to be on the path to becoming a pseudogene."" Structural similarity to OBPs does not confer odorant binding function - D7r5 has lost or never had functional binding activity."
ANOGA	GPRgr22	IPR013604	GO:0016020	membrane	ACCEPT	no		"This is a valid inference from the 7TM chemoreceptor domain. While ""plasma membrane"" (GO:0005886) is more specific, having both annotations is acceptable as the IEA annotation is independently derived from domain analysis."
ANOGA	GPRgr22	IPR013604	GO:0050909	sensory perception of taste	REMOVE	yes		Despite belonging to the gustatory receptor family, Gr22 functions in olfactory CO2 chemosensation, not taste. The receptor is expressed in maxillary palp sensilla that detect volatile CO2 for host-seeking behavior, not in taste sensilla on the proboscis. Literature consistently describes this as an olfactory pathway (Jones et al. 2007, Liu et al. 2020). The annotation is based on family nomenclature rather than actual function.
ANOGA	NPAC	IPR006115	GO:0050661	NADP binding	KEEP_AS_NON_CORE	yes		"The structural capacity to bind NADP is plausible given the Rossmann fold architecture, but the dehydrogenase domain is catalytically inert. Fang et al. (2013) reported ""attempts to identify the intrinsic enzymatic activity of NPAC as a potential dehydrogenase were unsuccessful."" The binding may be structural or regulatory rather than catalytic, and the functional significance of NADP binding is unclear. This is not a core function of the protein."
ANOGA	NPAC	IPR029154	GO:0051287	NAD binding	KEEP_AS_NON_CORE	yes		"The structural NAD binding capacity is plausible given the conserved Rossmann fold, but the domain serves as ""a catalytically inert oligomerization module"" rather than performing redox chemistry. NAD binding is not a core function of this protein."
ANOGA	PGRPLB	IPR006619	GO:0008270	zinc ion binding	ACCEPT	no		Correct annotation. PGRP-LB is a catalytic amidase that requires zinc for its enzymatic activity. The InterPro-based annotation correctly identifies PGRP-LB as a zinc-dependent enzyme, in contrast to non-catalytic PGRPs like PGRP-S1 which have lost the zinc-binding residues.
ANOGA	PGRPLB	IPR002502,IPR006619,IPR036505	GO:0008745	N-acetylmuramoyl-L-alanine amidase activity	ACCEPT	no		Correct annotation, duplicates the IBA annotation. PGRP-LB retains the catalytic residues required for amidase activity, unlike non-catalytic PGRPs like PGRP-S1. The IEA annotation from InterPro is well-supported by domain analysis.
ANOGA	PGRPLB	IPR002502,IPR006619,IPR036505	GO:0009253	peptidoglycan catabolic process	ACCEPT	no		Correct annotation. PGRP-LB enzymatically degrades peptidoglycan through its N-acetylmuramoyl-L-alanine amidase activity. This is a core biological process annotation that accurately reflects PGRP-LB's catalytic function.
ANOGA	PGRPLB	IPR017331	GO:0042834	peptidoglycan binding	ACCEPT	no		Correct annotation. PGRP-LB retains the peptidoglycan binding function through its PGRP domain. Substrate binding is essential for its catalytic amidase activity. The IEA annotation from InterPro is appropriate.
ANOGA	PGRPLC	IPR006619	GO:0008270	zinc ion binding	UNDECIDED	yes		"The InterPro PGRP domain annotation (IPR006619) suggests potential zinc binding based on structural homology to catalytic PGRPs. However, the deep research (file:ANOGA/PGRPLC/PGRPLC-deep-research-falcon.md) explicitly states PGRPLC is non-catalytic and ""no amidase activity reported."" Catalytic PGRPs require zinc for amidase activity, but non-catalytic PGRPs may have lost critical zinc-coordinating residues. Without specific structural data for Anopheles PGRPLC showing zinc coordination, this annotation remains uncertain."
ANOGA	PGRPLC	IPR002502,IPR006619,IPR036505	GO:0008745	N-acetylmuramoyl-L-alanine amidase activity	REMOVE	yes		Same rationale as for the IBA annotation above. The InterPro domains (IPR002502, IPR006619, IPR036505) are structural domains that can be present in both catalytic and non-catalytic PGRPs. PGRPLC uses this fold for peptidoglycan binding and receptor function, NOT for enzymatic hydrolysis. The literature explicitly confirms this is a non-catalytic receptor PGRP (file:ANOGA/PGRPLC/PGRPLC-deep-research-falcon.md).
ANOGA	PGRPLC	IPR002502,IPR006619,IPR036505	GO:0009253	peptidoglycan catabolic process	REMOVE	yes		This annotation is a logical consequence of the incorrect amidase activity annotation. Since PGRPLC is a non-catalytic receptor, it does not participate in peptidoglycan catabolism. It binds peptidoglycan to initiate signaling, but binding is not catabolism. The correct process annotation is the peptidoglycan recognition protein signaling pathway (GO:0061057) or immune response (file:ANOGA/PGRPLC/PGRPLC-deep-research-falcon.md).
ANOGA	PGRPLD	IPR006619	GO:0008270	zinc ion binding	UNDECIDED	yes		While catalytic PGRPs bind zinc at the active site, the absence of key catalytic residues in PGRP-LD raises uncertainty about whether zinc binding is retained. No direct experimental evidence confirms zinc binding in this non-catalytic PGRP. The annotation may be a case of domain-based over-annotation.
ANOGA	PGRPLD	IPR002502,IPR006619,IPR036505	GO:0008745	N-acetylmuramoyl-L-alanine amidase activity	REMOVE	yes		This is a classic example of domain-based over-annotation. The presence of an Amidase_2 domain (IPR002502) led to automatic annotation of amidase activity, but detailed sequence analysis shows PGRP-LD lacks the conserved residues required for catalysis. Not all PGRP family members are enzymatically active; many function as pattern recognition receptors or immune regulators without catalytic activity. The functional evidence clearly indicates PGRP-LD is non-catalytic.
ANOGA	PGRPLD	IPR002502,IPR006619,IPR036505	GO:0009253	peptidoglycan catabolic process	REMOVE	yes		This annotation logically follows from the incorrect amidase activity annotation. Since PGRP-LD lacks amidase catalytic activity, it cannot participate in peptidoglycan catabolic processes. The annotation should be removed along with the amidase activity annotation.
ANOGA	PGRPLD		GO:0016021	integral component of membrane	NEW	no		The UniProt entry shows transmembrane domain prediction by Phobius. Functional studies describe PGRP-LD as a transmembrane PGRP at the gut barrier.
ANOGA	PGRPS1	IPR006619	GO:0008270	zinc ion binding	REMOVE	yes		The InterPro-based annotation assumes all PGRP domain proteins bind zinc, but this is only true for catalytic amidase PGRPs. PGRP-S1 lacks the conserved His/Cys residues that coordinate the catalytic zinc. Without these residues, there is no functional zinc-binding site. This is an over-annotation based on domain presence.
ANOGA	PGRPS1	IPR002502,IPR006619,IPR036505	GO:0008745	N-acetylmuramoyl-L-alanine amidase activity	REMOVE	yes		Over-annotation based on domain presence. The InterPro domains (IPR002502, IPR006619, IPR036505) correctly identify this as a PGRP family member, but PGRP-S1 specifically lacks the catalytic residues. Only PGRP-S2 and PGRP-S3 in A. gambiae retain amidase activity.
ANOGA	PGRPS1	IPR002502,IPR006619,IPR036505	GO:0009253	peptidoglycan catabolic process	REMOVE	yes		PGRP-S1 is a non-catalytic receptor that recognizes but does not degrade peptidoglycan. Peptidoglycan catabolism is carried out by catalytic PGRPs (S2, S3, LB in Anopheles) that retain amidase activity. This is an over-annotation based on domain rather than verified function.
ANOGA	PGRPS1	IPR017331	GO:0042834	peptidoglycan binding	ACCEPT	no		Correct annotation. PGRP-S1 retains the peptidoglycan binding function even though it lacks catalytic activity. The PGRP domain enables recognition and binding of bacterial cell wall components. The IEA annotation from InterPro is appropriate. This is a valid additional annotation alongside the more specific receptor activity term.
ANOGA	PGRPS2	IPR006619	GO:0008270	zinc ion binding	ACCEPT	no		PGRPS2 contains the conserved zinc-binding residues (His-His-Tyr-Cys motif) found in all catalytically active PGRPs. This is supported by domain architecture and sequence conservation patterns. Zinc binding is integral to the amidase catalytic mechanism.
ANOGA	PGRPS2	IPR002502,IPR006619,IPR036505	GO:0008745	N-acetylmuramoyl-L-alanine amidase activity	ACCEPT	no		Strong evidence from domain conservation, sequence analysis showing intact zinc-binding residues, and evolutionary constraint (purifying selection) supports amidase activity. Unlike PGRPS1, PGRPS2 retains all critical catalytic residues.
ANOGA	PGRPS2	IPR002502,IPR006619,IPR036505	GO:0009253	peptidoglycan catabolic process	ACCEPT	no		This biological process annotation is the appropriate consequence of the molecular function (amidase activity). If PGRPS2 has amidase activity as supported by domain conservation and sequence analysis, it would participate in peptidoglycan catabolism.
ANOGA	PGRPS2	IPR017331	GO:0042834	peptidoglycan binding	ACCEPT	no		Peptidoglycan binding is a defining characteristic of all PGRP family members. PGRPS2 has a well-defined PGRP domain that is structurally homologous to the peptidoglycan-binding domains of characterized family members.
ANOGA	PGRPS3	IPR006619	GO:0008270	zinc ion binding	ACCEPT	no		Well-supported by comparative sequence analysis. Multiple studies confirm that among Anopheles short PGRPs, S2 and S3 retain the zinc-coordinating catalytic residues while S1 does not. The InterPro-based annotation correctly identifies PGRP-S3 as a zinc-binding protein due to its functional amidase domain.
ANOGA	PGRPS3	IPR002502,IPR006619,IPR036505	GO:0008745	N-acetylmuramoyl-L-alanine amidase activity	ACCEPT	no		Core molecular function annotation. Multiple comparative analyses confirm PGRP-S3 retains the zinc-coordinating catalytic residues characteristic of functional amidases. This distinguishes it from the non-catalytic PGRP-S1 in the same organism. The InterPro annotation is appropriate for this catalytically active PGRP.
ANOGA	PGRPS3	IPR002502,IPR006619,IPR036505	GO:0009253	peptidoglycan catabolic process	ACCEPT	no		Consistent with the molecular function annotation. Since PGRP-S3 has predicted amidase activity (unlike the non-catalytic PGRP-S1), it is expected to participate in peptidoglycan catabolism. This process-level annotation appropriately follows from the catalytic function.
ANOGA	PGRPS3	IPR017331	GO:0042834	peptidoglycan binding	ACCEPT	no		Correct annotation. The PGRP domain mediates peptidoglycan binding in all members of this protein family. For amidase-type PGRPs, this binding function is prerequisite to the catalytic activity. The IEA annotation from InterPro is appropriate.
ANOGA	SRPN2	IPR000215	GO:0005615	extracellular space	ACCEPT	no		Accurate annotation derived from serpin domain presence. Serpins of this type are typically secreted, and SRPN2 has been experimentally confirmed to be secreted into the hemolymph.
ANOGA	TDO	IPR037217	GO:0046872	metal ion binding	KEEP_AS_NON_CORE	yes		Technically correct because TDO binds heme iron, but the term is overly general. The more specific GO:0020037 (heme binding) already captures this function accurately. Metal ion binding is not independently informative for this protein.
ANOGA	TEP1	IPR001599,IPR002890	GO:0004866	endopeptidase inhibitor activity	REMOVE	yes		TEP1 is a thioester-containing protein that functions as an opsonin in the insect complement-like pathway, not as a protease inhibitor. While it shares structural domains with alpha-2-macroglobulin proteins, its functional mechanism is different. No experimental evidence supports endopeptidase inhibitor activity. This appears to be an over-annotation based on domain homology.
ANOGA	TEP10	IPR001599,IPR002890	GO:0004866	endopeptidase inhibitor activity	REMOVE	yes		"The annotation represents an inappropriate transfer of vertebrate A2M function to an arthropod TEP. The deep research confirms insect TEPs function as ""complement C3-like opsonins"" rather than protease inhibitors. The UniProt function annotation explicitly states TEP10 ""Binds covalently through a thioester bond to the pathogen surface resulting in pathogen clearance"" - this is opsonin function, not protease inhibition. There is no evidence that arthropod TEPs inhibit endopeptidases; their A2M-like domains have been repurposed for immune opsonization."
ANOGA	TEP2	IPR001599,IPR002890	GO:0004866	endopeptidase inhibitor activity	REMOVE	yes		TEP2 is a thioester-containing protein that functions as a predicted complement-like opsonin in the insect innate immune pathway, not as a protease inhibitor. While it shares alpha-2-macroglobulin domains with protease inhibitors, the TEP family has diverged to function primarily in pathogen opsonization rather than protease inhibition. This is well established for TEP1 in A. gambiae and applies by homology to TEP2. The annotation represents an over-annotation based solely on domain homology without consideration of the functional divergence of the TEP family. This is the same issue identified for TEP1 annotation review.
ANOGA	TEP6	IPR001599,IPR002890	GO:0004866	endopeptidase inhibitor activity	REMOVE	yes		"The InterPro2GO mapping from A2M domains to endopeptidase inhibitor activity is inappropriate for insect TEPs. This represents a classic case of over-annotation based on domain homology without considering functional divergence. Key evidence against protease inhibitor function: (1) Insect TEPs function as complement-like opsonins, not protease inhibitors. (2) TEP1 (the best-characterized family member) binds to pathogen surfaces via thioester bonds and promotes killing through melanization, not through protease inhibition. (3) The UniProt function annotation states the protein ""Binds covalently through a thioester bond to the pathogen surface resulting in pathogen clearance"" - describing opsonization, not protease inhibition. (4) The LRIM1/APL1C-TEP axis in Anopheles is established as a complement-like pathway. No literature supports protease inhibitor activity for any insect TEP."
ANOGA	TOLL9	IPR000157	GO:0007165	signal transduction	MODIFY	yes	GO:0008063 Toll signaling pathway	While this annotation correctly reflects that the TIR domain enables signal transduction function, the more specific term GO:0008063 (Toll signaling pathway) should be used instead, consistent with the review of the IBA annotation for the same GO term. The TIR domain in TOLL9 specifically mediates Toll pathway signaling.
ARAHY	A0A444Z7V7	IPR005150	GO:0016020	membrane	KEEP_AS_NON_CORE	yes		InterPro-derived annotation from the cellulose synthase domain (IPR005150). Correct but uninformative given more specific membrane annotations already present.
ARAHY	A0A444Z7V7	IPR005150	GO:0016760	cellulose synthase (UDP-forming) activity	MODIFY	yes	GO:0051753 mannan synthase activity	The protein is classified in the plant cellulose synthase-like D subfamily per UniProt. CSLD proteins synthesize mannans and glucomannans rather than cellulose. The cellulose synthase (UDP-forming) activity term is a mis-annotation arising from the broad IPR005150 domain covering the entire CESA/CSL superfamily.
ARAHY	A0A444Z7V7	IPR005150	GO:0030244	cellulose biosynthetic process	MODIFY	yes	GO:0071555 cell wall organization	CSLD proteins synthesize mannans/glucomannans, which are hemicellulose components, not cellulose. A more appropriate process term would be mannan biosynthetic process or cell wall organization.
ARATH	AAU94417	IPR002683	GO:0005509	calcium ion binding	KEEP_AS_NON_CORE	yes		PSBP domain proteins are known to bind calcium ions, which is important for OEC stabilization. However, this is IEA (automatic annotation) and needs experimental verification. The primary function is not calcium binding per se but stabilization of the OEC.
ARATH	AAU94417	IPR002683	GO:0009654	photosystem II oxygen evolving complex	ACCEPT	no		"Correct and specific localization. PSBP-1 is a core component of the OEC. [PMID:9039496 ""23-kDa polypeptide of oxygen-evolving complex""]"
ARATH	AAU94417	IPR002683	GO:0019898	extrinsic component of membrane	ACCEPT	no		"Correct. PSBP-1 is an extrinsic (peripheral) component associated with the thylakoid membrane via the PSII complex. [PMID:11719511 ""PsbP domain proteins""]"
ARATH	ABI1	IPR015655	GO:0004722	protein serine/threonine phosphatase activity	ACCEPT	no		protein serine/threonine phosphatase activity is a core molecular/process annotation for ABI1 phosphatase function.
ARATH	ABI1	IPR000222	GO:0043169	cation binding	MARK_AS_OVER_ANNOTATED	yes		The generic cation-binding term is much less informative than PP2C protein Ser/Thr phosphatase activity.
ARATH	ABI5	IPR004827,IPR043452,IPR046347	GO:0003700	DNA-binding transcription factor activity	ACCEPT	no		Core molecular function. Established by cloning of ABI5 as a bZIP TF whose DNA-binding/dimerization domains are required for function, and by direct promoter binding and transactivation assays.
ARATH	ABI5	IPR043452	GO:0045893	positive regulation of DNA-templated transcription	ACCEPT	no		Core function. ABI5 activates transcription of ABRE-containing target genes such as RD29B and Em1/Em6.
ARATH	AG	IPR033896	GO:0000977	RNA polymerase II transcription regulatory region sequence-specific DNA binding	ACCEPT	no		Although this InterPro-derived annotation is electronic, it is consistent with direct AG evidence. AG binds DNA regulatory elements in target loci and controls Pol II-transcribed developmental genes.
ARATH	AG	IPR002100,IPR036879	GO:0003677	DNA binding	MODIFY	yes	GO:0000978 RNA polymerase II cis-regulatory region sequence-specific DNA binding	The annotation is directionally correct but too broad. It should be replaced by the more informative cis-regulatory, sequence-specific Pol II DNA-binding term already supported for AG.
ARATH	AG	IPR002487	GO:0003700	DNA-binding transcription factor activity	MODIFY	yes	GO:0000981 DNA-binding transcription factor activity, RNA polymerase II-specific	AG regulates nuclear developmental genes transcribed by RNA polymerase II. GO:0000981 better captures the same core molecular function with the appropriate Pol II specificity.
ARATH	AG	IPR002487	GO:0005634	nucleus	ACCEPT	no		AG must access chromatin to carry out its core transcriptional regulatory function. The electronic InterPro-derived nucleus annotation is supported by UniProt and by experimental evidence that AG-containing MADS complexes operate in the nucleus.
ARATH	AG	IPR002487	GO:0006355	regulation of DNA-templated transcription	MODIFY	yes	GO:0006357 regulation of transcription by RNA polymerase II	In a eukaryotic nuclear transcription factor context, GO:0006357 is the more precise BP term. AG regulates Pol II target genes during floral organogenesis and meristem termination.
ARATH	AG	IPR033896	GO:0045944	positive regulation of transcription by RNA polymerase II	ACCEPT	no		The annotation is supported as one arm of AG function: AG induces downstream genes and positive-feedback components during stamen and carpel development. It should not be read as AG's only transcriptional effect, because AG also mediates repression during meristem termination.
ARATH	AG	IPR002100,IPR036879	GO:0046983	protein dimerization activity	ACCEPT	no		Protein dimerization is a core molecular property of AG rather than a generic incidental interaction. UniProt records AG homodimerization and heterodimerization with SEPALLATA/AGL proteins, and experimental studies support SEP-dependent multimeric AG-containing complexes.
ARATH	AGO1	IPR003165,IPR036397	GO:0003676	nucleic acid binding	MODIFY	yes	GO:0004521 RNA endonuclease activity; GO:0035198 miRNA binding; GO:0035197 siRNA binding	The informative molecular functions are small-RNA guide binding and PIWI-domain RNA slicing, not generic nucleic acid binding.
ARATH	AGO1	IPR003100	GO:0003723	RNA binding	MODIFY	yes	GO:0004521 RNA endonuclease activity; GO:0035198 miRNA binding; GO:0035197 siRNA binding	RNA binding is directionally correct but less specific than miRNA binding, siRNA binding, and RNA endonuclease activity.
ARATH	AP1	IPR033896	GO:0000977	RNA polymerase II transcription regulatory region sequence-specific DNA binding	MODIFY	yes	GO:0000978 RNA polymerase II cis-regulatory region sequence-specific DNA binding	The annotation is directionally correct but less precise than the existing AP1 IBA term. Replace with the more specific cis-regulatory region binding term supported by AP1 ChIP evidence.
ARATH	AP1	IPR002100,IPR036879	GO:0003677	DNA binding	MODIFY	yes	GO:0000978 RNA polymerase II cis-regulatory region sequence-specific DNA binding	Replace generic DNA binding with AP1's specific RNA polymerase II cis-regulatory region sequence-specific DNA binding activity.
ARATH	AP1	IPR002487	GO:0003700	DNA-binding transcription factor activity	MODIFY	yes	GO:0000981 DNA-binding transcription factor activity, RNA polymerase II-specific	AP1 regulates Pol II-transcribed developmental genes; GO:0000981 is the more specific molecular-function replacement for this generic transcription factor activity term.
ARATH	AP1	IPR002487	GO:0005634	nucleus	ACCEPT	no		Nuclear localization is consistent with domain-based inference, UniProt, and experimental AP1-containing MADS complex studies.
ARATH	AP1	IPR002487	GO:0006355	regulation of DNA-templated transcription	MODIFY	yes	GO:0006357 regulation of transcription by RNA polymerase II	The broad term should be replaced by regulation of transcription by RNA polymerase II to reflect AP1's target gene context.
ARATH	AP1	IPR033896	GO:0045944	positive regulation of transcription by RNA polymerase II	KEEP_AS_NON_CORE	yes		Retain as a valid context-specific activity, but do not treat it as AP1's full core function because AP1 has both activating and repressing roles.
ARATH	AP1	IPR002100,IPR036879	GO:0046983	protein dimerization activity	ACCEPT	no		Although broad, this term captures a real molecular capability needed for AP1's MADS complex activity. More specific heterodimerization is proposed for individual generic protein-binding rows where the source supports a particular MADS partner interaction.
ARATH	AP2	IPR016177	GO:0003677	DNA binding	MODIFY	yes	GO:0003700 DNA-binding transcription factor activity; GO:0000976 transcription cis-regulatory region binding	Replace generic DNA binding with terms that capture AP2's actual molecular role: a DNA-binding transcription factor that binds transcriptional cis-regulatory regions.
ARATH	AP2	IPR001471,IPR036955	GO:0003700	DNA-binding transcription factor activity	ACCEPT	no		The term accurately represents AP2's core molecular activity.
ARATH	AP2	IPR001471,IPR036955	GO:0006355	regulation of DNA-templated transcription	ACCEPT	no		This broad BP term is correct for AP2 because AP2 directly regulates transcriptional targets in floral meristems, shoot meristems, and seed tissues.
ARATH	AP3	IPR033896	GO:0000977	RNA polymerase II transcription regulatory region sequence-specific DNA binding	KEEP_AS_NON_CORE	yes		Biologically correct but a less specific sibling/parent of GO:0000978 (cis-regulatory region binding), which already captures the core DNA-binding function; retain as non-core to avoid redundant emphasis.
ARATH	AP3	IPR002100,IPR036879	GO:0003677	DNA binding	KEEP_AS_NON_CORE	yes		True but uninformative parent term; the specific Pol II cis-regulatory binding and DNA-binding transcription factor activity annotations are preferred as the core molecular-function descriptors.
ARATH	AP3	IPR002487	GO:0003700	DNA-binding transcription factor activity	ACCEPT	no		AP3 is a bona fide sequence-specific DNA-binding transcription factor of the MADS-box family; this is a core molecular function (kept consistent with the ISS-supported annotations to the same term).
ARATH	AP3	IPR002487	GO:0006355	regulation of DNA-templated transcription	KEEP_AS_NON_CORE	yes		Correct but a high-level parent of GO:0006357 (regulation of transcription by RNA Pol II), which is retained as the core biological-process descriptor.
ARATH	AP3	IPR033896	GO:0045944	positive regulation of transcription by RNA polymerase II	KEEP_AS_NON_CORE	yes		"AP3 is an activator of specific targets (UniProt curates ""AP3/PI heterodimer activates the expression of NAP"", PMID:9489703), so positive regulation is real; however AP3/PI also represses targets (e.g. GNC/GNL), so the bidirectional ""regulation of transcription by RNA Pol II"" term better represents the core activity. Retained as non-core."
ARATH	AP3	IPR002100,IPR036879	GO:0046983	protein dimerization activity	ACCEPT	no		Obligate AP3/PI heterodimer formation (via the MADS and K-box/coiled-coil domains) is a genuinely core molecular function, not a peripheral inference; neither protein is active alone and heterodimerization precedes all downstream activity. UniProt curates the heterodimer; nuclear import requires AP3+PI co-expression (PMID:8698240).
ARATH	APO1	IPR023342	GO:0003723	RNA binding	ACCEPT	no		Consistent with higher-quality evidence (IDA and IBA) for the same function. The automated prediction correctly identified this core molecular function.
ARATH	ARF19	IPR010525,IPR044835	GO:0006355	regulation of DNA-templated transcription	ACCEPT	no		This annotation is accurate and reflects the core molecular function of ARF19. The IEA evidence appropriately captures the conserved domain-based inference.
ARATH	ARF19	IPR010525,IPR044835	GO:0009725	response to hormone	ACCEPT	no		"While ""response to auxin"" (GO:0009733) is more specific, the broader ""response to hormone"" is not incorrect. ARF19 also integrates ethylene signaling, so the broader term captures this additional hormone response role."
ARATH	ARF5	IPR003340,IPR010525,IPR044835	GO:0003677	DNA binding	MODIFY	yes	GO:1990837 sequence-specific double-stranded DNA binding	"ARF5 is a characterized sequence-specific TF that binds the AuxRE motif; the generic parent ""DNA binding"" should be sharpened to a sequence-specific DNA-binding term. The molecular function as an activator is captured separately by the DNA-binding transcription factor activity annotation."
ARATH	ARF5	IPR010525,IPR044835	GO:0006355	regulation of DNA-templated transcription	ACCEPT	no		ARF5/MP regulates transcription of auxin-responsive target genes. This broad process term is consistent with its role as a transcriptional activator that binds AuxREs and activates targets such as DRN, LFY and ANT. Acceptable as a general BP, though the more specific auxin-activated signaling pathway better captures its biology.
ARATH	ARF5	IPR010525,IPR044835	GO:0009725	response to hormone	MARK_AS_OVER_ANNOTATED	yes		Too general for a protein with a well-defined and specific auxin role; the specific auxin terms (response to auxin, auxin-activated signaling pathway) are preferred.
ARATH	AT1G06680	IPR002683	GO:0005509	calcium ion binding	MARK_AS_OVER_ANNOTATED	yes		Marked over-annotated because more specific terms capture the biology more accurately.
ARATH	AT1G06680	IPR002683	GO:0009654	photosystem II oxygen evolving complex	ACCEPT	no		Retained as the most specific core location; PsbP is one of the three plant OEC extrinsic proteins.
ARATH	AT1G06680	IPR002683	GO:0019898	extrinsic component of membrane	KEEP_AS_NON_CORE	yes		Kept as non-core to preserve potentially valid context-specific annotation without elevating it to core function.
ARATH	AT1G32330	IPR000232	GO:0003700	DNA-binding transcription factor activity	ACCEPT	no		This is a duplicate annotation of the same GO term with different evidence (IEA from InterPro vs IBA from phylogeny). Both are correct. Duplicate annotations with different evidence codes are acceptable in GO and provide complementary support for the same function.
ARATH	AT1G32330	IPR000232	GO:0006355	regulation of DNA-templated transcription	MODIFY	yes	GO:0045944 positive regulation of transcription by RNA polymerase II	While technically correct, this term is too general. HSFA1D specifically functions as a positive regulator (activator) of transcription, not a general regulator. The more specific term 'positive regulation of transcription by RNA polymerase II' (GO:0045944) would better capture the actual activity.
ARATH	AT1G32330	IPR000232	GO:0043565	sequence-specific DNA binding	ACCEPT	no		This annotation correctly captures the sequence-specific nature of HSFA1D DNA binding. The protein specifically recognizes HSE consensus sequences through its DNA-binding domain. This is a valid parent term that can coexist with more specific annotations (GO:0000978).
ARATH	AT1G74310	IPR003959	GO:0016887	ATP hydrolysis activity	ACCEPT	no		While this is a duplicate annotation with different evidence (IEA from InterPro vs IBA from phylogenetic inference), both correctly identify the same core function. It is acceptable to have the same GO term with different evidence codes, as they provide independent support for the annotation.
ARATH	AT2G26150	IPR000232	GO:0003700	DNA-binding transcription factor activity	ACCEPT	no		Same as IBA annotation - correctly captures core TF function. Redundant but consistent.
ARATH	AT2G26150	IPR000232	GO:0006355	regulation of DNA-templated transcription	ACCEPT	no		HSFA2 does regulate DNA-templated transcription as a core function. This broad term is accurate though less informative than the positive regulation term (GO:0045893) annotated elsewhere.
ARATH	AT2G26150	IPR000232	GO:0043565	sequence-specific DNA binding	ACCEPT	no		HSFA2 exhibits sequence-specific DNA binding to heat shock elements. This is a CORE molecular function supported by EMSA and ChIP experiments [PMID:19352026].
ARATH	AT3G02990	IPR000232	GO:0003700	DNA-binding transcription factor activity	ACCEPT	no		This is a duplicate annotation of GO:0003700 already annotated with IBA evidence (GO_REF:0000033). Both annotations are correct and represent core molecular function. The IEA annotation is based on InterPro domain mapping which correctly identifies the HSF DNA-binding domain. Having multiple evidence codes for the same accurate annotation is acceptable in GO.
ARATH	AT3G02990	IPR000232	GO:0006355	regulation of DNA-templated transcription	ACCEPT	no		This annotation accurately describes the core biological process function of HSFA1E. As a transcription factor, HSFA1E regulates DNA-templated transcription by binding to HSE sequences in target gene promoters and activating their expression. This includes genes encoding heat shock proteins, HSFA2, DREB2A, and other stress-responsive genes. The annotation is appropriate as a general biological process term.
ARATH	AT3G02990	IPR000232	GO:0043565	sequence-specific DNA binding	ACCEPT	no		This annotation correctly describes HSFA1E's sequence-specific DNA binding capability. The protein specifically recognizes the HSE palindromic sequence through its conserved DNA-binding domain with winged-helix structure. The specificity is achieved through direct base-specific hydrogen bonding in the major groove and DNA shape recognition mechanisms. This is well-supported by structural and functional studies.
ARATH	AT4G17750	IPR000232	GO:0003700	DNA-binding transcription factor activity	ACCEPT	no		This is a duplicate annotation of GO:0003700 which is already annotated with IBA evidence. Both annotations are correct and accurately describe HSFA1A's core function as a DNA-binding transcription factor. Having multiple lines of evidence (IBA and IEA) for the same term is acceptable and reinforces the confidence in the annotation. The IEA evidence comes from InterPro HSF domain recognition.
ARATH	AT4G17750	IPR000232	GO:0006355	regulation of DNA-templated transcription	ACCEPT	no		"This annotation is technically correct but quite general. HSFA1A is a transcriptional regulator, so this parent term is appropriate. The IEA evidence comes from InterPro domain recognition. More specific terms like ""cellular response to heat"" better capture HSFA1A's actual biological role, but this serves as an appropriate general classification in the GO hierarchy."
ARATH	AT4G17750	IPR000232	GO:0043565	sequence-specific DNA binding	ACCEPT	no		This annotation accurately describes HSFA1A's sequence-specific DNA-binding capability. The protein recognizes a specific consensus sequence (HSE) and binds with high specificity. PMID:7948881 demonstrates specific binding. The IEA evidence comes from InterPro domain recognition of the HSF DNA-binding domain, which is known to confer sequence-specific binding. This is a CORE molecular function.
ARATH	AT5G02500	IPR013126	GO:0016887	ATP hydrolysis activity	ACCEPT	no		Duplicate of IBA annotation for same term. Both IBA and IEA evidence support this core molecular function.
ARATH	AT5G03720	IPR000232	GO:0003700	DNA-binding transcription factor activity	ACCEPT	no		This is a redundant but valid annotation with different evidence code. Both IBA and IEA support the same accurate functional annotation. Keeping both provides evidence diversity.
ARATH	AT5G03720	IPR000232	GO:0006355	regulation of DNA-templated transcription	ACCEPT	no		This is an appropriate high-level biological process annotation that correctly captures HSFA3 role in transcriptional regulation. While more specific terms about heat acclimation are preferable, this general term is not incorrect.
ARATH	AT5G03720	IPR000232	GO:0043565	sequence-specific DNA binding	ACCEPT	no		Sequence-specific DNA binding is a core molecular function accurately describing HSFA3 activity. The protein recognizes specific HSE sequences through its helix-turn-helix DNA-binding domain. This IEA annotation based on InterPro domain analysis is well-supported.
ARATH	AT5G05410	IPR001471,IPR036955	GO:0003700	DNA-binding transcription factor activity	ACCEPT	no		This IEA annotation based on InterPro domain recognition is accurate and consistent with experimental IBA and IDA evidence for the same term. Computational annotation correctly identifies the core molecular function.
ARATH	AT5G05410	IPR001471,IPR036955	GO:0006355	regulation of DNA-templated transcription	MODIFY	yes	GO:0045893 positive regulation of DNA-templated transcription	"The more specific term ""positive regulation of DNA-templated transcription"" (GO:0045893) is already assigned with IBA evidence and better represents DREB2A's activator function rather than generic regulation."
ARATH	AT5G16820	IPR000232	GO:0003700	DNA-binding transcription factor activity	ACCEPT	no		IEA annotations based on InterPro domain mapping (GO_REF:0000002) are standard for proteins containing conserved domains associated with transcriptional function. HSFA1B contains the HSF_DNA-bind domain (Pfam PF00447, InterPro IPR000232), a signature domain of heat shock factors that mediates sequence-specific DNA binding and transcriptional activation. This is a duplicate annotation (GO:0003700) with different evidence code (IEA vs IBA), which is acceptable as the annotations derive from different evidence sources. The term accurately represents a core molecular function of HSFA1B.
ARATH	AT5G16820	IPR000232	GO:0006355	regulation of DNA-templated transcription	ACCEPT	no		HSFA1B directly regulates DNA-templated transcription by binding to heat shock element sequences and recruiting RNA polymerase II and associated transcriptional machinery. The IEA annotation based on InterPro domain mapping (IPR000232 - HSF DNA-binding domain) is appropriate for the HSF family. The deep research documents extensive transcriptional regulation: HSFA1B directly activates approximately 952 genes under various conditions and indirectly regulates approximately 1,780 additional genes through secondary transcription factors. Direct targets include heat shock proteins, developmental genes, and secondary transcription factors (HSFA2, DREB2A, HSFB2A, HSFB2B, MBF1C). This term accurately captures HSFA1B's role as a master regulator of transcriptional networks.
ARATH	AT5G16820	IPR000232	GO:0043565	sequence-specific DNA binding	ACCEPT	no		"HSFA1B demonstrates sequence-specific DNA binding to heat shock elements (HSEs), particularly the canonical (nGAAn)3 motif and the novel HSE1b variant (5'-AGAAnnTTCT-3'). The IEA annotation based on InterPro domain mapping (IPR000232) is appropriate for proteins containing the HSF DNA-binding domain, which mediates sequence-specific binding. The deep research extensively documents sequence specificity: ""Comparison of structural data between HSF1 and HSF2 suggests subtle but significant differences in DNA-binding geometry... The identification of the non-canonical HSE1b element represents a major advance in understanding HSFA1B target specificity... researchers demonstrated that HSFA1B specifically recognizes the HSE1b sequence in approximately 55 promoters."" This represents a more informative molecular function than generic ""DNA binding""."
ARATH	AT5G52640	IPR001404,IPR019805	GO:0006457	protein folding	KEEP_AS_NON_CORE	yes		Same as IBA annotation - too general and doesn't capture HSP90's specialized function. Redundant with other annotations. Keep as non-core.
ARATH	AT5G52640	IPR001404	GO:0016887	ATP hydrolysis activity	ACCEPT	no		Redundant with IBA annotation but correct. ATP hydrolysis is essential for the chaperone cycle.
ARATH	AT5G52640	IPR001404,IPR019805	GO:0051082	unfolded protein binding	MODIFY	yes	GO:0140662 ATP-dependent protein folding chaperone	Same issue as IBA annotation - technically inaccurate. HSP90.1 does not bind unfolded proteins in the classical sense. Should be replaced with more accurate term.
ARATH	AT5G52640	IPR001404	GO:0140662	ATP-dependent protein folding chaperone	ACCEPT	no		This term precisely describes HSP90.1's core molecular function. It is more specific and accurate than the general 'protein folding' or 'unfolded protein binding' terms. This should be considered the primary molecular function annotation.
ARATH	At1g67980	IPR002935	GO:0008171	O-methyltransferase activity	KEEP_AS_NON_CORE	yes		This is a parent term of caffeoyl-CoA O-methyltransferase activity and is redundant if the more specific term is retained. Keep as non-core since it is technically correct but adds no information beyond GO:0042409.
ARATH	BAK1	IPR000719,IPR001245,IPR008271	GO:0004672	protein kinase activity	MODIFY	yes	GO:0004675 transmembrane receptor protein serine/threonine kinase activity	The transmembrane receptor protein serine/threonine kinase activity term captures both the catalytic activity and receptor-like membrane context.
ARATH	BAK1	IPR000719,IPR017441	GO:0005524	ATP binding	KEEP_AS_NON_CORE	yes		This is compatible with kinase activity but less informative than receptor Ser/Thr kinase activity.
ARATH	BIK1	IPR000719,IPR001245,IPR008271	GO:0004672	protein kinase activity	MODIFY	yes	GO:0004674 protein serine/threonine kinase activity	Correct but general. BIK1 is a proven Ser/Thr (dual-specificity) protein kinase (EC 2.7.11.1); the more specific term protein serine/threonine kinase activity is preferred and is independently supported by experimental annotations.
ARATH	BIK1	IPR000719,IPR017441	GO:0005524	ATP binding	ACCEPT	no		BIK1 has a canonical protein kinase ATP-binding pocket (Gly-rich loop 73-81, catalytic Lys-105). Mutation of Lys-105 (with Lys-106) gives a kinase-dead enzyme, confirming functional ATP binding. Standard supporting MF for an active kinase.
ARATH	BRI1	IPR000719,IPR008271	GO:0004672	protein kinase activity	ACCEPT	no		BRI1 has dual-specificity protein kinase activity that phosphorylates both serine/threonine and tyrosine residues. This is a fundamental molecular function.
ARATH	BZR1	IPR033264	GO:0003700	DNA-binding transcription factor activity	ACCEPT	no		Core molecular function, supported by IEA (InterPro IPR033264) and independently by IDA (PMID:21074725) and biochemical work (PMID:15681342).
ARATH	BZR1	IPR033264	GO:0006351	DNA-templated transcription	MODIFY	yes	GO:0006355 regulation of DNA-templated transcription	BZR1 regulates transcription of target genes (acting as repressor/activator) rather than carrying out the transcription reaction. Replace with regulation of DNA-templated transcription.
ARATH	BZR1	IPR033264	GO:0009742	brassinosteroid mediated signaling pathway	ACCEPT	no		Core biological process; matches strong experimental evidence (also annotated IMP from PMID:11970900).
ARATH	CBF1	IPR016177	GO:0003677	DNA binding	ACCEPT	no		The InterPro-based IEA to DNA binding is correct and is corroborated by direct experimental evidence (gel-shift). DNA binding is a true parent of the more specific sequence-specific binding; retained. More specific terms are proposed as new terms.
ARATH	CBF1	IPR001471,IPR036955,IPR045277	GO:0003700	DNA-binding transcription factor activity	ACCEPT	no		Strongly supported by both InterPro/ISS and direct experimental evidence of sequence-specific DNA binding combined with transactivation.
ARATH	CBF1	IPR001471,IPR036955	GO:0006355	regulation of DNA-templated transcription	ACCEPT	no		Correct but general parent term; the more specific positive regulation of transcription is also annotated (IDA) and accepted. Retained as a valid grouping term.
ARATH	CER1	IPR006694	GO:0005506	iron ion binding	ACCEPT	no		This annotation correctly captures CER1's iron ion binding through its conserved histidine-rich motifs that coordinate the di-iron active site. This is a core molecular function essential for catalytic activity.
ARATH	CER1	IPR006694	GO:0008610	lipid biosynthetic process	MARK_AS_OVER_ANNOTATED	yes		Redundant generic parent of the specific and correctly supported biological process terms (wax/alkane biosynthetic process).
ARATH	CER1	IPR006694	GO:0016491	oxidoreductase activity	MARK_AS_OVER_ANNOTATED	yes		Redundant generic parent of the specific and correct molecular function GO:0071771. The decarbonylation reaction is redox-coupled (NADPH/O2-dependent), but the specific term better captures the actual catalysis.
ARATH	CERK1	IPR000719,IPR001245,IPR008271	GO:0004672	protein kinase activity	MARK_AS_OVER_ANNOTATED	yes		The annotation is biochemically correct but is subsumed by the more specific and experimentally supported protein serine/threonine kinase activity (GO:0004674). It is retained as a non-misleading parent term.
ARATH	CERK1	IPR000719,IPR017441	GO:0005524	ATP binding	ACCEPT	no		Consistent with the conserved kinase ATP-binding motif and experimentally demonstrated kinase/autophosphorylation activity requiring ATP.
ARATH	CERK1	IPR044812	GO:0019199	transmembrane receptor protein kinase activity	ACCEPT	no		Supported by domain architecture and the experimental demonstration that ligand-induced receptor dimerization activates kinase signaling (duplicate IDA/IMP annotations below).
ARATH	CHL1	IPR018456	GO:0006857	oligopeptide transport	REMOVE	yes		Family-level (InterPro) over-annotation. CHL1/NRT1.1 recognizes specifically nitrate and chlorate but NOT the di-peptide Ala-Ala (UniProt FUNCTION), so peptide transport is not a function of this protein. The PTR family name reflects ancestry, not CHL1 substrate specificity.
ARATH	CHL1	IPR000109,IPR018456	GO:0022857	transmembrane transporter activity	MODIFY	yes	GO:0015112 nitrate transmembrane transporter activity	Too general. The specific, experimentally established molecular function is nitrate transmembrane transporter activity (GO:0015112), already annotated (IMP). Replace the generic parent with the specific child.
ARATH	CHL1	IPR000109	GO:0055085	transmembrane transport	MODIFY	yes	GO:0015706 nitrate transmembrane transport	Too general. The specific, experimentally established process is nitrate transmembrane transport (GO:0015706), already annotated (IMP). Replace the generic parent with the specific child.
ARATH	CIPK24	IPR000719,IPR008271	GO:0004672	protein kinase activity	ACCEPT	no		CIPK24 is a genuine active kinase with an N-terminal SNF1-like catalytic domain; autophosphorylation demonstrates protein kinase activity. This is a core molecular function.
ARATH	CIPK24	IPR000719,IPR017441	GO:0005524	ATP binding	ACCEPT	no		ATP binding is integral to the core kinase activity; supported by the conserved ATP-binding lysine and by abolition of activity in the K40N mutant.
ARATH	CIPK24	IPR004041,IPR018451	GO:0007165	signal transduction	MARK_AS_OVER_ANNOTATED	yes		The specific role is calcium-mediated CBL-CIPK signaling driving ion homeostasis; the bare 'signal transduction' term adds little. More specific salt-stress and ion-transport regulation terms capture the function.
ARATH	CLV1	IPR000719,IPR001245,IPR008271	GO:0004672	protein kinase activity	MODIFY	yes	GO:0004674 protein serine/threonine kinase activity	Replace the generic kinase term with the more informative Ser/Thr protein kinase term already supported by direct assays and EC mapping.
ARATH	CLV1	IPR000719	GO:0005524	ATP binding	KEEP_AS_NON_CORE	yes		Keep as a mechanistic cofactor-binding annotation for the kinase domain, but the core function is Ser/Thr receptor kinase signaling.
ARATH	CLV3	IPR044962	GO:0033612	receptor serine/threonine kinase binding	ACCEPT	no		The mature CLV3 (MCLV3/CLV3p) peptide is the ligand for the LRR receptor serine/threonine kinases CLV1/BAM1/BAM2; receptor kinase binding is the core molecular function and is experimentally supported.
ARATH	CO	IPR000315	GO:0008270	zinc ion binding	KEEP_AS_NON_CORE	yes		Zinc ion binding is a conserved structural feature of the BBX domains and supports protein folding/interaction capacity, but it is not the main biological function of CO.
ARATH	CO	IPR045281	GO:0009909	regulation of flower development	MODIFY	yes	GO:0048578 positive regulation of long-day photoperiodism, flowering	Replace with positive regulation of long-day photoperiodism, flowering using Arabidopsis experimental evidence rather than a broad domain-only flower-development mapping.
ARATH	CRY1	IPR014134	GO:0009882	blue light photoreceptor activity	ACCEPT	no		This captures the core CRY1 role as a blue/UV-A photoreceptor that mediates blue-light signaling and photomorphogenesis.
ARATH	CRY1	IPR014134	GO:0009785	blue light signaling pathway	ACCEPT	no		This captures the core CRY1 role as a blue/UV-A photoreceptor that mediates blue-light signaling and photomorphogenesis.
ARATH	CRY2	IPR014134	GO:0009882	blue light photoreceptor activity	ACCEPT	no		CRY2 is a plant cryptochrome whose FAD-dependent blue-light photoactivation drives dimerization, photobody formation, and downstream signaling.
ARATH	CRY2	IPR014134	GO:0009785	blue light signaling pathway	ACCEPT	no		CRY2 photoactivation, homodimerization, photobody formation, and interaction with signaling partners such as BIC1, SPA1, and CIBs are central to blue-light signaling.
ARATH	DCL1	IPR006935	GO:0003677	DNA binding	REMOVE	yes		DCL1 is a pri-/pre-miRNA-processing RNase III enzyme whose accessible evidence supports RNA substrate recognition, not DNA binding.
ARATH	DCL1	IPR003100,IPR011907	GO:0003723	RNA binding	MODIFY	yes	GO:0004525 ribonuclease III activity; GO:0003725 double-stranded RNA binding	RNA binding is true but less specific than DCL1 ribonuclease III activity and double-stranded RNA binding in pri-/pre-miRNA processing.
ARATH	DCL1	IPR000999,IPR011907,IPR036389	GO:0004525	ribonuclease III activity	ACCEPT	no		RNase III activity is the core catalytic molecular function by which DCL1 cleaves pri-/pre-miRNA hairpins.
ARATH	DCL1	IPR006935	GO:0005524	ATP binding	KEEP_AS_NON_CORE	yes		ATP binding is plausible from domain architecture, but the curated core function is RNase III-mediated miRNA precursor cleavage.
ARATH	DCL1	IPR011907	GO:0006364	rRNA processing	REMOVE	yes		DCL1 literature and UniProt function support miRNA/siRNA precursor processing, not a primary rRNA-processing role.
ARATH	DCL1	IPR000999,IPR036389	GO:0006396	RNA processing	MODIFY	yes	GO:0004525 ribonuclease III activity; GO:0031053 primary miRNA processing	Use DCL1-specific ribonuclease III activity and primary miRNA processing rather than broad RNA processing or generic hydrolase activity.
ARATH	DCL1	IPR006935	GO:0016787	hydrolase activity	MODIFY	yes	GO:0004525 ribonuclease III activity; GO:0031053 primary miRNA processing	Use DCL1-specific ribonuclease III activity and primary miRNA processing rather than broad RNA processing or generic hydrolase activity.
ARATH	DCL1	IPR005034	GO:0016891	RNA endonuclease activity producing 5'-phosphomonoesters, hydrolytic mechanism	MODIFY	yes	GO:0004525 ribonuclease III activity; GO:0031053 primary miRNA processing	Use DCL1-specific ribonuclease III activity and primary miRNA processing rather than broad RNA processing or generic hydrolase activity.
ARATH	DRB1	IPR044450,IPR044451	GO:0003725	double-stranded RNA binding	ACCEPT	no		Double-stranded RNA binding is the core molecular function of DRB1/HYL1.
ARATH	DREB2A	IPR016177	GO:0003677	DNA binding	KEEP_AS_NON_CORE	yes		Correct but general; subsumed by the specific sequence-specific DNA-binding transcription factor activity and DRE/CRT cis-regulatory region binding annotations.
ARATH	DREB2A	IPR001471,IPR036955	GO:0003700	DNA-binding transcription factor activity	ACCEPT	no		DREB2A is an experimentally validated DNA-binding transcription factor; this electronic annotation is corroborated by IDA (PMID:9707537) and ISS annotations to the same term.
ARATH	DREB2A	IPR001471,IPR036955	GO:0006355	regulation of DNA-templated transcription	KEEP_AS_NON_CORE	yes		General process term subsumed by the more specific positive regulation of DNA-templated transcription annotation supported by IDA.
ARATH	EDS1	IPR002921	GO:0006629	lipid metabolic process	REMOVE	yes		EDS1 is an immune signaling pseudoenzyme/scaffold; no direct lipid metabolic process or lipid substrate is established.
ARATH	EDS1	IPR044214	GO:0006952	defense response	MARK_AS_OVER_ANNOTATED	yes		The broad defense response term blurs the specific EDS1 immune signaling role captured by more precise experimental annotations.
ARATH	EFR	IPR000719,IPR017441	GO:0005524	ATP binding	ACCEPT	no		ATP binding is required for the kinase activity; consistent with the protein kinase ATP-binding site annotated in UniProt.
ARATH	EIN2	IPR001046	GO:0046873	metal ion transmembrane transporter activity	REMOVE	yes		The NRAMP-like N-terminal domain is insufficient to infer metal transporter activity for EIN2; UniProt also notes that EIN2 is probably not involved in iron uptake.
ARATH	EIN2	IPR017187	GO:0009873	ethylene-activated signaling pathway	ACCEPT	no		Although electronically inferred, the annotation matches the core, experimentally established function of EIN2.
ARATH	EIN2	IPR001046	GO:0030001	metal ion transport	REMOVE	yes		No EIN2-specific transport activity is demonstrated, and family-level transfer from canonical NRAMP transporters is misleading.
ARATH	EIN2	IPR001046	GO:0016020	membrane	MODIFY	yes	GO:0005789 endoplasmic reticulum membrane	The generic membrane term should be replaced by the specific, supported ER membrane location.
ARATH	ELF4	IPR040462	GO:0042753	positive regulation of circadian rhythm	ACCEPT	no		This is a core function of ELF4. Multiple experimental studies confirm ELF4 promotes circadian rhythm maintenance [PMID:12214234, PMID:20357892].
ARATH	ETR1	IPR003661,IPR036097	GO:0000155	phosphorelay sensor kinase activity	ACCEPT	no		ETR1 functions as a histidine kinase with autophosphorylation activity that is inhibited by ethylene binding. This phosphorelay activity is essential for its role as negative regulator of ethylene signaling.
ARATH	ETR1	IPR014525	GO:0004672	protein kinase activity	MARK_AS_OVER_ANNOTATED	yes		GO:0004672 (protein kinase activity) is a direct parent of GO:0004673 (protein histidine kinase activity) in the GO hierarchy, and GO:0004673 is already annotated three times (IEA, IMP, TAS). Retaining the generic parent over-annotates the gene; a MODIFY to GO:0004673 would merely duplicate the existing specific annotation.
ARATH	ETR1	IPR003661,IPR036097	GO:0007165	signal transduction	MARK_AS_OVER_ANNOTATED	yes		The specific child term GO:0009873 (ethylene-activated signaling pathway) is already captured as a separate accepted annotation. Retaining the generic parent GO:0007165 (signal transduction) over-annotates the gene without adding specificity; a MODIFY to GO:0009873 would merely duplicate the existing annotation.
ARATH	ETR1	IPR014525	GO:0009723	response to ethylene	ACCEPT	no		ETR1 is fundamentally involved in ethylene response as the receptor that detects and responds to ethylene. This is a core biological process for ETR1.
ARATH	ETR1	IPR004358	GO:0016772	transferase activity, transferring phosphorus-containing groups	MARK_AS_OVER_ANNOTATED	yes		GO:0016772 is a direct ancestor of GO:0004673 (protein histidine kinase activity) in the GO hierarchy (GO:0016772 > GO:0016301 kinase activity > ... > GO:0004673), which is already captured. For consistency with the over-annotation call on its parent GO:0016740 (transferase activity), this uninformative intermediate term is also marked as over-annotated.
ARATH	ETR1	IPR014525	GO:0038199	ethylene receptor activity	ACCEPT	no		ETR1 is definitively an ethylene receptor. This is its primary function and already confirmed by IBA evidence. Additional evidence codes support this core function.
ARATH	FAD2	IPR005804	GO:0006629	lipid metabolic process	ACCEPT	no		Correct but general. FAD2 functions in glycerolipid/fatty acid metabolism; the specific unsaturated fatty acid biosynthetic role is captured below.
ARATH	FAD2	IPR012171	GO:0016491	oxidoreductase activity	ACCEPT	no		Correct but general. The informative molecular function is the omega-6 (Delta-12) fatty acid desaturase activity captured by more specific terms below.
ARATH	FAD2	IPR021863	GO:0016717	oxidoreductase activity, acting on paired donors, with oxidation of a pair of donors resulting in the reduction of molecular oxygen to two molecules of water	ACCEPT	no		Correct enzyme-class molecular function for a membrane fatty acid desaturase, which uses O2 and an electron donor (cytochrome b5) to introduce a double bond. Consistent with the specific desaturase annotations.
ARATH	FAE1	IPR012392,IPR013601	GO:0016020	membrane	ACCEPT	no		Correct but general. FAE1 is an integral membrane protein of the ER (UniProt annotates transmembrane helices); the ER annotation is the informative localization.
ARATH	FAE1	IPR016039	GO:0016746	acyltransferase activity	ACCEPT	no		Correct but general. As a 3-ketoacyl-CoA synthase (condensing enzyme), FAE1 is an acyltransferase, but fatty acid elongase activity (GO:0009922) is the informative molecular function.
ARATH	FAE1	IPR012392,IPR013601	GO:0016747	acyltransferase activity, transferring groups other than amino-acyl groups	ACCEPT	no		Correct but general; this is the acyltransferase parent matching the KCS condensation chemistry. The specific fatty acid elongase activity annotation is retained as the core function.
ARATH	FER	IPR000719,IPR001245,IPR008271	GO:0004672	protein kinase activity	ACCEPT	no		Correct molecular function, also supported experimentally (IDA, PMID:17673660). The more precise core MF is the receptor serine/threonine kinase activity, but the general protein kinase activity term is accurate.
ARATH	FER	IPR045272	GO:0004714	transmembrane receptor protein tyrosine kinase activity	MODIFY	yes	GO:0004675 transmembrane receptor protein serine/threonine kinase activity	This IEA derives from InterPro IPR045272 (ANXUR1/2-like) mapped through a generic Tyr/Ser-Thr catalytic-domain signature (Pfam PK_Tyr_Ser-Thr). UniProt and Rhea assign FER only Ser/Thr activity (EC 2.7.11.1), and plant CrRLK1Ls are Ser/Thr (RD) kinases. The correct receptor molecular function is transmembrane receptor protein serine/threonine kinase activity (GO:0004675), which also captures the single-pass transmembrane receptor architecture.
ARATH	FER	IPR000719,IPR017441	GO:0005524	ATP binding	KEEP_AS_NON_CORE	yes		Correct cofactor-binding function supporting the kinase activity; FER has a defined ATP-binding site (residues 542-550 and Lys-565). Standard supporting MF for an active kinase rather than a core distinguishing function.
ARATH	FLC	IPR033896	GO:0000977	RNA polymerase II transcription regulatory region sequence-specific DNA binding	ACCEPT	no		FLC binds to specific regulatory regions (CArG boxes) in RNA polymerase II-transcribed gene promoters. Confirmed by ChIP assays showing direct binding to FT and SOC1 promoters.
ARATH	FLC	IPR002487	GO:0003700	DNA-binding transcription factor activity	ACCEPT	no		FLC is a classic DNA-binding transcription factor with a MADS-box domain. Functions as a transcriptional repressor by binding specific DNA sequences and modulating transcription of target genes.
ARATH	FLC	IPR002487	GO:0006355	regulation of DNA-templated transcription	ACCEPT	no		FLC regulates DNA-templated transcription by acting as a transcriptional repressor of key floral integrator genes. Functions through chromatin-based mechanisms and direct DNA binding.
ARATH	FLC	IPR033896	GO:0045944	positive regulation of transcription by RNA polymerase II	MODIFY	yes	GO:0000122 negative regulation of transcription by RNA polymerase II	This annotation is incorrect. FLC functions primarily as a transcriptional repressor, not an activator. It negatively regulates transcription of floral integrator genes.
ARATH	FLC	IPR002100,IPR036879	GO:0046983	protein dimerization activity	ACCEPT	no		FLC forms homo- and heterodimeric complexes with other MADS-box proteins (FLM, MAF2, MAF3) through its MADS-box domain. These interactions are essential for functional transcriptional repression.
ARATH	FLS2	IPR000719,IPR008271	GO:0004672	protein kinase activity	MODIFY	yes	GO:0004675 transmembrane receptor protein serine/threonine kinase activity	A more specific experimentally and domain-supported term exists for this protein.
ARATH	FLS2	IPR000719	GO:0005524	ATP binding	KEEP_AS_NON_CORE	yes		The annotation is compatible with the kinase domain but is less informative than the receptor protein serine/threonine kinase activity.
ARATH	GI	IPR026211	GO:2000028	regulation of photoperiodism, flowering	KEEP_AS_NON_CORE	yes		Keep as a correct electronic family-level annotation, but prioritize the experimentally supported GO:0048578 term as core.
ARATH	GID1A	IPR002168,IPR013094	GO:0016787	hydrolase activity	REMOVE	yes		GID1 was explicitly described as similar to the hormone-sensitive lipase family but WITHOUT hydrolase activity. The protein binds GA as a receptor in a pocket on the hydrolase fold rather than catalyzing hydrolysis. The nominal UniProt EC=3.-.-.- and InterPro fold mapping produce a spurious catalytic MF annotation that does not reflect the true (receptor) function.
ARATH	GIP1	IPR022214	GO:0000931	gamma-tubulin ring complex	ACCEPT	no		Retained as supported or plausible for this gene and evidence context.
ARATH	GIP1	IPR022214	GO:0033566	gamma-tubulin complex localization	ACCEPT	no		Captures GIP1's central, experimentally supported role in recruiting/anchoring gamma-tubulin complexes to MT nucleation sites.
ARATH	GL2	IPR017970	GO:0000981	DNA-binding transcription factor activity, RNA polymerase II-specific	ACCEPT	no		The term captures the core transcription-factor role more specifically than generic DNA binding.
ARATH	GL2	IPR001356	GO:0003677	DNA binding	MODIFY	yes	GO:0000976 transcription cis-regulatory region binding	Use transcription cis-regulatory region binding to capture promoter/regulatory DNA binding by the transcription factor.
ARATH	GL2	IPR002913	GO:0008289	lipid binding	MARK_AS_OVER_ANNOTATED	yes		Without direct GL2 ligand evidence, lipid binding is an over-projected domain annotation relative to the supported transcription-factor role.
ARATH	GL2	IPR017970	GO:0006355	regulation of DNA-templated transcription	MODIFY	yes	GO:0006357 regulation of transcription by RNA polymerase II	Regulation of transcription by RNA polymerase II is the better process context for a plant nuclear transcription factor.
ARATH	GL3	IPR011598,IPR036638	GO:0046983	protein dimerization activity	ACCEPT	no		Dimerization is a conserved and functionally relevant property of bHLH transcription factors.
ARATH	HEN1	IPR046357	GO:0003755	peptidyl-prolyl cis-trans isomerase activity	REMOVE	yes		The PPIase-like/FKBP-like domain is present, but no evidence supports HEN1 peptidyl-prolyl isomerase catalytic activity; the supported biochemical function is small-RNA methyltransferase activity.
ARATH	HEN1	IPR026610	GO:0008171	O-methyltransferase activity	MODIFY	yes	GO:0090486 small RNA 2'-O-ribose methyltransferase activity	Use the small-RNA terminal 2-prime-O-methyltransferase term to capture HEN1 substrate and reaction specificity.
ARATH	HEN1	IPR026610	GO:0008173	RNA methyltransferase activity	MODIFY	yes	GO:0090486 small RNA 2'-O-ribose methyltransferase activity	Use the small-RNA terminal 2-prime-O-methyltransferase term to capture HEN1 substrate and reaction specificity.
ARATH	HKT1	IPR003445	GO:0006812	monoatomic cation transport	MODIFY	yes	GO:0006814 sodium ion transport	Correct in essence (HKT1 transports a monovalent cation) but too general. The physiologically relevant species transported in planta is Na+, so a sodium ion transport term is more informative.
ARATH	HKT1	IPR003445	GO:0008324	monoatomic cation transmembrane transporter activity	MODIFY	yes	GO:0015081 sodium ion transmembrane transporter activity	Correct but too general. The experimentally demonstrated and core molecular function is sodium ion transmembrane transporter activity; replace the generic parent with the specific Na+ term.
ARATH	HKT1	IPR004773	GO:0015079	potassium ion transmembrane transporter activity	MARK_AS_OVER_ANNOTATED	yes		This K+-specific molecular-function term is inherited from the HKT/Trk/Ktr family signature and the wheat ortholog's high-affinity K+ behavior, but AtHKT1;1 is Na+-selective and does NOT transport K+ in planta (it lacks the conserved Gly-68 of K+-permeable HKTs; only a <2-fold K+ effect in heterologous systems). The potassium transport function is therefore an over-annotation. The correct Na+ molecular function is captured separately by the ACCEPTed GO:0015081 (sodium ion transmembrane transporter activity, IDA), so this K+ term is flagged as over-annotated rather than re-pointed at the Na+ term — consistent with the three parallel K+ biological-process annotations in this file, which are likewise marked as over-annotated.
ARATH	HKT1	IPR003445	GO:0055085	transmembrane transport	MODIFY	yes	GO:0035725 sodium ion transmembrane transport	Correct but far too general to be informative; replace with the specific sodium ion transmembrane transport process.
ARATH	HKT1	IPR004773	GO:0071805	potassium ion transmembrane transport	MARK_AS_OVER_ANNOTATED	yes		Family/name-derived electronic inference. AtHKT1;1 does not transport K+ in planta; any K+ effect is indirect via Na+ homeostasis. Direct K+ transmembrane transport is an over-annotation. The biologically relevant process is sodium ion transmembrane transport (already annotated via GO:0035725).
ARATH	HY5	IPR044280	GO:0000981	DNA-binding transcription factor activity, RNA polymerase II-specific	ACCEPT	no		This annotation accurately represents HY5s primary molecular function. HY5 is a well-characterized transcription factor that binds to G-box and other cis-regulatory elements and regulates transcription by RNA polymerase II. This is supported by extensive ChIP-seq and biochemical studies demonstrating direct DNA binding and transcriptional activation.
ARATH	HY5	IPR004827,IPR046347	GO:0003700	DNA-binding transcription factor activity	ACCEPT	no		This annotation correctly represents HY5s primary molecular function as a DNA-binding transcription factor. While the more specific GO:0000981 term provides additional precision about RNA polymerase II specificity, this general term is still accurate and appropriate. Multiple evidence types for this core function are acceptable.
ARATH	HY5	IPR004827,IPR046347	GO:0006355	regulation of DNA-templated transcription	ACCEPT	no		This annotation correctly describes HY5s role in regulating transcription. While general, it accurately captures the biological process in which HY5 participates. This term is appropriately broad and complements the more specific molecular function annotations.
ARATH	HY5	IPR044280	GO:0045944	positive regulation of transcription by RNA polymerase II	ACCEPT	no		This annotation correctly captures HY5s biological function. HY5 primarily acts as a transcriptional activator, promoting the expression of target genes involved in photomorphogenesis, light responses, and chloroplast development. This is a well-established function supported by extensive experimental evidence.
ARATH	LFY	IPR002910,IPR035209	GO:0003677	DNA binding	MODIFY	yes	GO:0000976 transcription cis-regulatory region binding	InterPro domain evidence and experimental literature support a more informative term than generic DNA binding. LFY should be represented as binding transcriptional cis-regulatory DNA, with separate annotations capturing sequence-specific DNA binding and transcription factor activity.
ARATH	LFY	IPR002910	GO:0006355	regulation of DNA-templated transcription	MODIFY	yes	GO:0045944 positive regulation of transcription by RNA polymerase II	LFY is best captured as a positive transcriptional regulator of RNA-polymerase-II target genes, rather than the nonspecific parent process.
ARATH	LHY	IPR006447	GO:0003677	DNA binding	KEEP_AS_NON_CORE	yes		LHY is a genuine MYB DNA-binding protein, so the term is correct, but it is a generic parent superseded by GO:0003700 (DNA-binding transcription factor activity, IDA) and GO:0000976 (cis-regulatory region binding, IDA). Retain as supporting, non-core.
ARATH	MPK6	IPR000719,IPR008271	GO:0004672	protein kinase activity	ACCEPT	no		Accurate parent-level molecular function annotation. MPK6 is a bona fide protein kinase (EC 2.7.11.24); the kinase domain spans residues 63-348. More specific MF terms are also present.
ARATH	MPK6	IPR000719,IPR003527,IPR017441	GO:0005524	ATP binding	ACCEPT	no		Well-supported by sequence and structure; MPK6 binds ATP at the canonical kinase pocket and the K92 invariant lysine is essential for catalysis (K92M abolishes activity).
ARATH	MUTE	IPR044283	GO:0003700	DNA-binding transcription factor activity	ACCEPT	no		Consistent with experimental and ISS evidence that MUTE is a functional bHLH transcription factor; this is a core molecular function.
ARATH	MUTE	IPR044283	GO:0010052	guard cell differentiation	ACCEPT	no		Core biological process; strongly supported by loss- and gain-of-function data even though the GOA evidence here is electronic.
ARATH	MUTE	IPR011598,IPR036638	GO:0046983	protein dimerization activity	MODIFY	yes	GO:0046982 protein heterodimerization activity	Experimental evidence (Y2H and BiFC in epidermal nuclei) shows MUTE associates with the broadly expressed bHLH-LZ proteins ICE1/SCRM and SCRM2, indicating heterodimerization activity rather than generic dimerization. This is a core molecular function.
ARATH	MYC2	IPR045084	GO:0003700	DNA-binding transcription factor activity	ACCEPT	no		DNA-binding transcription factor activity is a direct molecular function of MYC2 and is central to its transcription factor role.
ARATH	MYC2	IPR011598,IPR036638	GO:0046983	protein dimerization activity	KEEP_AS_NON_CORE	yes		Oligomerization may influence DNA binding and transcriptional regulation but is secondary to MYC2's transcription factor role.
ARATH	MYC2	IPR045084	GO:0006355	regulation of DNA-templated transcription	ACCEPT	no		Transcriptional regulation is a core biological role of MYC2 as a bHLH transcription factor.
ARATH	NCED3	IPR004294	GO:0016702	oxidoreductase activity, acting on single donors with incorporation of molecular oxygen, incorporation of two atoms of oxygen	KEEP_AS_NON_CORE	yes		Correct dioxygenase classification from InterPro IPR004294, but subsumed by the more specific MF term GO:0045549, which represents the core molecular function.
ARATH	NEK3	IPR000719,IPR008271	GO:0004672	protein kinase activity	MODIFY	yes	GO:0004674 protein serine/threonine kinase activity	The more specific term GO:0004674 (protein serine/threonine kinase activity) is already annotated and better represents the function. NEK kinases are Ser/Thr-specific kinases, so the general protein kinase activity term should be replaced with the specific one.
ARATH	NEK3	IPR000719,IPR017441	GO:0005524	ATP binding	ACCEPT	no		ATP binding is a fundamental requirement for kinase activity. The domain architecture clearly supports this annotation, with conserved ATP-binding motifs identified by PROSITE and InterPro.
ARATH	NPR1	IPR044292	GO:0009862	systemic acquired resistance, salicylic acid mediated signaling pathway	ACCEPT	no		This represents NPR1s primary and best-characterized function. NPR1 was originally identified as the key regulator of SAR and SA signaling. This annotation captures its core biological role [PMID:9019406, PMID:17172357, PMID:32788727]
ARATH	NPR1	IPR044292	GO:2000022	regulation of jasmonic acid mediated signaling pathway	ACCEPT	no		JA regulation is a well-established function of NPR1, representing the negative regulatory aspect of SA-JA crosstalk. This is experimentally supported [PMID:12615947, PMID:26269953]
ARATH	NPR1	IPR044292	GO:2000031	regulation of salicylic acid mediated signaling pathway	ACCEPT	no		This is a core NPR1 function - NPR1 is the key positive regulator of SA signaling pathway. This annotation accurately captures NPR1s primary role [PMID:9019406, PMID:12615947, PMID:32788727]
ARATH	OST1	IPR000719,IPR017441	GO:0005524	ATP binding	ACCEPT	no		Standard, well-supported molecular function for an ATP-dependent kinase; ATP-binding residues are defined structurally and by mutagenesis.
ARATH	P14713	IPR003661	GO:0000155	phosphorelay sensor kinase activity	KEEP_AS_NON_CORE	yes		Domain present but regulatory activity primarily through PIF interactions, not kinase activity.
ARATH	P14713	IPR001294,IPR012129,IPR013515,IPR013654,IPR013767	GO:0006355	regulation of DNA-templated transcription	KEEP_AS_NON_CORE	yes		Generic term. More specific negative regulation term exists.
ARATH	P14713	IPR003661	GO:0007165	signal transduction	KEEP_AS_NON_CORE	yes		More specific terms describe PHYB's role in red/far-red light signaling.
ARATH	P14713	IPR001294,IPR013515	GO:0009584	detection of visible light	ACCEPT	no		Parent term. PHYB detects visible light (red/far-red region).
ARATH	P14713	IPR012129	GO:0017006	protein-tetrapyrrole linkage	ACCEPT	no		Parent term of phytochromobilin linkage. Chromophore is a tetrapyrrole.
ARATH	P14713	IPR012129	GO:0042803	protein homodimerization activity	ACCEPT	no		Core function. PHYB functions as a homodimer, confirmed by crystal structure.
ARATH	P93002	IPR044292	GO:0009862	systemic acquired resistance, salicylic acid mediated signaling pathway	ACCEPT	no		Computational annotation consistent with experimental evidence
ARATH	P93002	IPR044292	GO:2000022	regulation of jasmonic acid mediated signaling pathway	ACCEPT	no		Computational annotation consistent with experimental evidence
ARATH	P93002	IPR044292	GO:2000031	regulation of salicylic acid mediated signaling pathway	ACCEPT	no		Computational annotation consistent with experimental evidence
ARATH	PAD4	IPR002921	GO:0006629	lipid metabolic process	REMOVE	yes		PAD4 is an EDS1-family immune signaling protein; no direct lipid metabolic process or lipid substrate is established.
ARATH	PAL1	IPR008948	GO:0003824	catalytic activity	MODIFY	yes	GO:0045548 phenylalanine ammonia-lyase activity	GO:0003824 is uninformative for an enzyme whose exact reaction is experimentally established (L-phenylalanine = (E)-cinnamate + NH4+). Replace with the specific catalytic term GO:0045548.
ARATH	PAL1	IPR005922	GO:0006559	L-phenylalanine catabolic process	ACCEPT	no		PAL1 consumes L-phenylalanine, deaminating it to trans-cinnamate; this is the committed entry reaction. L-phenylalanine catabolic process is an accurate biological-process annotation for the enzyme's direct reaction.
ARATH	PAL1	IPR005922,IPR022313	GO:0016841	ammonia-lyase activity	MODIFY	yes	GO:0045548 phenylalanine ammonia-lyase activity	GO:0016841 is a more general parent of the known activity; replace with the specific GO:0045548 phenylalanine ammonia-lyase activity.
ARATH	PHYA	IPR003661	GO:0000155	phosphorelay sensor kinase activity	MODIFY	yes	GO:0004672 protein kinase activity	The domain-derived phosphorelay term is too specific and mechanistically misleading for plant PHYA.
ARATH	PHYA	IPR012129	GO:0009881	photoreceptor activity	MODIFY	yes	GO:0031516 far-red light photoreceptor activity	Replace the broad photoreceptor term with the more specific far-red light photoreceptor activity.
ARATH	PHYA	IPR012129	GO:0042803	protein homodimerization activity	KEEP_AS_NON_CORE	yes		Retain as an accurate non-core molecular property.
ARATH	PHYA	IPR001294,IPR012129,IPR013515,IPR013654,IPR013767	GO:0006355	regulation of DNA-templated transcription	ACCEPT	no		Retain as a core biological output of PHYA phototransduction, with the caveat that the molecular function is photoreceptor/kinase activity rather than direct DNA binding.
ARATH	PHYA	IPR003661	GO:0007165	signal transduction	MODIFY	yes	GO:0010018 far-red light signaling pathway; GO:0009585 red, far-red light phototransduction	Use PHYA-specific light signaling process terms.
ARATH	PHYA	IPR001294,IPR013515	GO:0009584	detection of visible light	ACCEPT	no		Visible-light detection is inherent to PHYA photoreceptor activity.
ARATH	PHYA	IPR012129	GO:0009585	red, far-red light phototransduction	ACCEPT	no		Red/far-red phototransduction is a core PHYA process.
ARATH	PHYA	IPR012129	GO:0017006	protein-tetrapyrrole linkage	KEEP_AS_NON_CORE	yes		Retain as a non-core property required for photoreceptor function.
ARATH	PHYB	IPR003661	GO:0000155	phosphorelay sensor kinase activity	ACCEPT	no		PHYB contains a well-characterized histidine kinase domain (residues 934-1153) that is conserved across phytochrome family members. Phosphorelay kinase activity is a core molecular function supported by structural and domain analysis.
ARATH	PHYB	IPR001294,IPR012129,IPR013515,IPR013654,IPR013767	GO:0006355	regulation of DNA-templated transcription	ACCEPT	no		Transcriptional regulation is a fundamental biological process for PHYB function. Well-supported by extensive evidence for PHYB role in regulating gene expression through PIF interactions.
ARATH	PHYB	IPR003661	GO:0007165	signal transduction	ACCEPT	no		Signal transduction is the core biological process that defines PHYB function as a photoreceptor. Well-supported by extensive evidence for light signal transduction mechanisms.
ARATH	PHYB	IPR001294,IPR013515	GO:0009584	detection of visible light	ACCEPT	no		Detection of visible light is a fundamental molecular function of PHYB. Specifically detects red (660-670nm) and far-red (720-740nm) light through phytochromobilin chromophore.
ARATH	PHYB	IPR012129	GO:0017006	protein-tetrapyrrole linkage	MODIFY	yes	GO:0017012 protein-phytochromobilin linkage	While accurate, the more specific term GO:0017012 (protein-phytochromobilin linkage) better describes the specific tetrapyrrole (phytochromobilin) that PHYB binds.
ARATH	PHYB	IPR012129	GO:0042803	protein homodimerization activity	ACCEPT	no		Homodimerization activity is a core molecular function of PHYB, confirmed by structural studies and essential for photoreceptor activity. This is more specific than generic protein binding.
ARATH	PI	IPR033896	GO:0000977	RNA polymerase II transcription regulatory region sequence-specific DNA binding	ACCEPT	no		Accurate for a MADS-box TF; PI binds sequence-specific cis-regulatory DNA. Slightly redundant with GO:0000978 but biologically correct.
ARATH	PI	IPR002100,IPR036879	GO:0003677	DNA binding	ACCEPT	no		PI binds DNA via its MADS domain; this is correct, though more specific sequence-specific DNA binding terms better capture the function.
ARATH	PI	IPR002487	GO:0003700	DNA-binding transcription factor activity	ACCEPT	no		DNA-binding transcription factor activity is the defining molecular function of this MADS-box protein.
ARATH	PI	IPR002487	GO:0006355	regulation of DNA-templated transcription	ACCEPT	no		PI regulates transcription of floral target genes; the term is accurate though general.
ARATH	PI	IPR033896	GO:0045944	positive regulation of transcription by RNA polymerase II	MARK_AS_OVER_ANNOTATED	yes		PI acts as both an activator and a repressor of RNA Pol II targets; the activator-only directional term is not generally accurate and over-states a single regulatory direction inferred electronically from domain signatures.
ARATH	PI	IPR002100,IPR036879	GO:0046983	protein dimerization activity	ACCEPT	no		AP3/PI obligate heterodimerization is essential for PI function; dimerization is therefore a core molecular function, consistent with project guidance to retain PI/AP3 heterodimerization as core.
ARATH	PIF3	IPR044273	GO:0003700	DNA-binding transcription factor activity	ACCEPT	no		Supported by direct experimental evidence (IDA) for DNA-binding transcription factor activity and sequence-specific DNA binding; consistent with the bHLH domain and G-box binding.
ARATH	PIF3	IPR044273	GO:0006355	regulation of DNA-templated transcription	ACCEPT	no		PIF3 directly binds promoters and activates/represses transcription of light-responsive genes; the general transcription-regulation term is correct and supported by more specific experimental annotations.
ARATH	PIF3	IPR011598,IPR036638	GO:0046983	protein dimerization activity	ACCEPT	no		PIF3 forms homodimers and heterodimerizes with other PIFs via its HLH domain, supported by interaction data.
ARATH	PIF4	IPR044273	GO:0003700	DNA-binding transcription factor activity	ACCEPT	no		Sequence-specific DNA-binding transcription factor activity is the defining, experimentally established molecular function of PIF4; the IEA InterPro mapping is strongly corroborated by direct evidence.
ARATH	PIF4	IPR044273	GO:0006355	regulation of DNA-templated transcription	MODIFY	yes	GO:0006357 regulation of transcription by RNA polymerase II	The annotation is correct but generic; PIF4 is a Pol II transcription factor, so the RNA polymerase II-specific term better captures its role.
ARATH	PIF4	IPR011598,IPR036638	GO:0046983	protein dimerization activity	ACCEPT	no		Protein dimerization is a core molecular function of bHLH transcription factors and is experimentally documented for PIF4 (homodimerization for DNA binding; HFR1 heterodimerization).
ARATH	PIN1	IPR004776	GO:0016020	membrane	KEEP_AS_NON_CORE	yes		Correct but a broad parent of the more specific (and experimentally supported) plasma membrane term; retained as non-core background.
ARATH	PIN1	IPR004776	GO:0055085	transmembrane transport	KEEP_AS_NON_CORE	yes		Accurate but generic; the more precise auxin-transport terms capture the core function. Retained as a correct broad parent.
ARATH	Q9XIR4	IPR023342	GO:0003723	RNA binding	ACCEPT	no		Computational annotation based on InterPro domain, supported by experimental evidence
ARATH	RBOHD	IPR013623	GO:0004601	peroxidase activity	REMOVE	yes		The catalytic activity of RBOHD is electron transfer from NADPH to O2 to generate superoxide (and downstream H2O2 by dismutation), not peroxidase activity. The InterPro-derived peroxidase keyword is a known mis-mapping for the gp91phox family and over-annotates the gene. The informative catalytic term is GO:0016175 (added as NEW).
ARATH	RBOHD	IPR002048	GO:0005509	calcium ion binding	ACCEPT	no		Well supported by conserved EF-hand domains/Ca2+ binding sites in UniProt and by the calcium-dependence of RBOH oxidase activity. This is a core molecular function contributing to activity regulation.
ARATH	RBOHD	IPR000778,IPR013112,IPR013121,IPR017927	GO:0016491	oxidoreductase activity	ACCEPT	no		Correct but high-level; acceptable as a broad IEA parent of the informative term GO:0016175. Not the core descriptor on its own.
ARATH	RBOHD	IPR013623	GO:0050664	oxidoreductase activity, acting on NAD(P)H, oxygen as acceptor	ACCEPT	no		Accurate and reasonably specific; consistent with the NADPH-binding ferredoxin-reductase module and O2-reducing oxidase activity. The product-specific child term GO:0016175 is added as NEW.
ARATH	RCA	IPR003959	GO:0005524	ATP binding	ACCEPT	no		ATP binding is a well-established, structurally and experimentally documented core function of Rubisco activase as an AAA+ ATPase.
ARATH	RCA	IPR003959	GO:0016887	ATP hydrolysis activity	ACCEPT	no		ATP hydrolysis is the energy-yielding step driving Rubisco reactivation and is intrinsic to RCA function.
ARATH	RDR6	IPR035979	GO:0003676	nucleic acid binding	MODIFY	yes	GO:0003968 RNA-directed RNA polymerase activity	RDR6 specifically uses RNA templates to synthesize RNA in secondary-siRNA pathways; RNA-directed RNA polymerase activity is the precise MF term.
ARATH	RDR6	IPR007855	GO:0003968	RNA-directed RNA polymerase activity	ACCEPT	no		RNA-directed RNA polymerase activity is the core molecular function of RDR6.
ARATH	RPM1	IPR002182	GO:0043531	ADP binding	KEEP_AS_NON_CORE	yes		ADP binding is mechanistically relevant, but RPM1's core gene-level role is immune receptor signaling rather than nucleotide binding alone.
ARATH	RPM1	IPR044974	GO:0006952	defense response	MODIFY	yes	GO:0042742 defense response to bacterium	Defense response to bacterium better captures the experimentally supported RPM1 output than generic defense response.
ARATH	RPS2	IPR002182	GO:0043531	ADP binding	KEEP_AS_NON_CORE	yes		ADP binding is plausible and mechanistically relevant for the NLR switch, but the core gene-level role is immune receptor signaling rather than nucleotide binding alone.
ARATH	SEP3	IPR033896	GO:0000977	RNA polymerase II transcription regulatory region sequence-specific DNA binding	ACCEPT	no		SEP3 is a MADS-box transcription factor that binds CArG-box regulatory DNA. This electronically inferred term is consistent with both the domain architecture and direct DNA-binding studies.
ARATH	SEP3	IPR002100,IPR036879	GO:0003677	DNA binding	MODIFY	yes	GO:0000978 RNA polymerase II cis-regulatory region sequence-specific DNA binding	InterPro domain mappings support a MADS-box DNA-binding protein, but SEP3 should be annotated to the more informative RNA-polymerase-II cis-regulatory region sequence-specific DNA-binding term.
ARATH	SEP3	IPR002487	GO:0003700	DNA-binding transcription factor activity	MODIFY	yes	GO:0000981 DNA-binding transcription factor activity, RNA polymerase II-specific	SEP3 regulates transcription of nuclear protein-coding target genes and belongs to the MADS-box/MEF2 transcription-factor family. GO:0000981 is a more specific and current replacement for this generic transcription factor activity.
ARATH	SEP3	IPR002100,IPR036879	GO:0046983	protein dimerization activity	MODIFY	yes	GO:0042803 protein homodimerization activity; GO:0046982 protein heterodimerization activity	UniProt and experimental studies support both SEP3 homomerization and heteromerization with other floral MADS proteins. Using the specific replacement terms improves functional precision.
ARATH	SEP3	IPR002487	GO:0006355	regulation of DNA-templated transcription	MODIFY	yes	GO:0006357 regulation of transcription by RNA polymerase II	SEP3 is a nuclear DNA-binding transcription factor regulating protein-coding floral targets. GO:0006357 is the better general process term and is also present in the phylogenetic GOA set.
ARATH	SEP3	IPR033896	GO:0045944	positive regulation of transcription by RNA polymerase II	ACCEPT	no		The positive-regulation term is supported by SEP3 target-gene and chromatin-remodeler recruitment studies. It should be retained while also recognizing that SEP3 may bind co-repressors in some complexes.
ARATH	SEP3	IPR002487	GO:0005634	nucleus	ACCEPT	no		SEP3 functions at nuclear cis-regulatory DNA. Multiple independent sources support a nuclear location.
ARATH	SOC1	IPR033896	GO:0000977	RNA polymerase II transcription regulatory region sequence-specific DNA binding	ACCEPT	no		This sequence-specific RNA polymerase II regulatory-region DNA-binding activity is consistent with conserved MADS-box domains and with direct SOC1 promoter-binding evidence.
ARATH	SOC1	IPR002100,IPR036879	GO:0003677	DNA binding	MODIFY	yes	GO:0000978 RNA polymerase II cis-regulatory region sequence-specific DNA binding	Replace generic DNA binding with RNA polymerase II cis-regulatory region sequence-specific DNA binding, which captures the MADS-box regulatory DNA-binding activity.
ARATH	SOC1	IPR002487	GO:0003700	DNA-binding transcription factor activity	MODIFY	yes	GO:0000981 DNA-binding transcription factor activity, RNA polymerase II-specific	SOC1 regulates RNA polymerase II-transcribed developmental genes, so GO:0000981 is the better molecular-function term.
ARATH	SOC1	IPR002100,IPR036879	GO:0046983	protein dimerization activity	ACCEPT	no		Protein dimerization is a core molecular mechanism for SOC1 transcription factor function, although partner-specific annotations should preferably use heterodimerization when evidence identifies the partner.
ARATH	SOC1	IPR002487	GO:0006355	regulation of DNA-templated transcription	MODIFY	yes	GO:0006357 regulation of transcription by RNA polymerase II	Replace with regulation of transcription by RNA polymerase II, which matches SOC1's nuclear transcriptional regulatory role.
ARATH	SOC1	IPR033896	GO:0045944	positive regulation of transcription by RNA polymerase II	ACCEPT	no		Positive regulation of RNA polymerase II transcription is a core aspect of SOC1's activity as a floral-transition transcription factor.
ARATH	SOC1	IPR002487	GO:0005634	nucleus	ACCEPT	no		Nuclear localization is well supported for functional SOC1 transcription factor complexes.
ARATH	SOS1	IPR006153,IPR018422	GO:0006812	monoatomic cation transport	ACCEPT	no		InterPro-based generic cation-transport term is accurate; it is broader than the specific sodium transport terms but not misleading, so it is retained.
ARATH	SOS1	IPR006153	GO:0015297	antiporter activity	ACCEPT	no		The InterPro-derived term is a correct parent of GO:0015385 (sodium:proton antiporter activity); the more specific term is also annotated, so this broader term is acceptable as-is.
ARATH	SOS1	IPR018422	GO:0015385	sodium:proton antiporter activity	ACCEPT	no		Strong convergent evidence (InterPro/IBA, UniProt catalytic activity, and functional yeast complementation showing Na+-specific transport) supports GO:0015385 as the central molecular function. It is the most informative MF term available and represents the core activity.
ARATH	SOS1	IPR006153,IPR018422	GO:0016020	membrane	ACCEPT	no		InterPro-derived generic membrane localization is accurate; the specific plasma-membrane term is also annotated, so this broader term is retained as-is.
ARATH	SOS1	IPR006153	GO:0055085	transmembrane transport	ACCEPT	no		InterPro-based generic transmembrane-transport term is accurate and consistent with the antiporter mechanism; retained as a non-misleading parent.
ARATH	SOS1	IPR006153,IPR018422	GO:1902600	proton transmembrane transport	ACCEPT	no		The curated catalytic activity explicitly involves H+ counter-transport (RHEA:29419), so proton transmembrane transport is a correct InterPro-derived annotation, consistent with the electroneutral antiport reaction.
ARATH	SPC24	IPR044951	GO:0051983	regulation of chromosome segregation	ACCEPT	no		Correct in direction and consistent with the experimental annotation to the identical term. SPC24/NDC80-complex proteins are required for accurate chromosome segregation and contribute to spindle-checkpoint regulation [PMID:29356153]. Retained as a valid (if redundant) electronic annotation.
ARATH	SPCH	IPR044283	GO:0003700	DNA-binding transcription factor activity	MARK_AS_OVER_ANNOTATED	yes	GO:0001216 DNA-binding transcription activator activity	Biologically correct family-level term, but superseded by the more specific and experimentally supported GO:0001216. Retained as supporting evidence rather than core; the specific MF term is preferred.
ARATH	SPCH	IPR044283	GO:0010052	guard cell differentiation	MARK_AS_OVER_ANNOTATED	yes		Family-propagated term that conflates the three stomatal bHLHs; SPCH's specific role is initiation/asymmetric division, whereas guard cell differentiation is FAMA's terminal step. A stomatal-lineage term is more precise.
ARATH	SPCH	IPR011598,IPR036638	GO:0046983	protein dimerization activity	ACCEPT	no		bHLH heterodimerization with SCRM/ICE1 and SCRM2 is required for SPCH DNA-binding and transactivation activity and is a core molecular function.
ARATH	STM	IPR017970	GO:0000981	DNA-binding transcription factor activity, RNA polymerase II-specific	ACCEPT	no		STM's best-supported core MF is RNA polymerase II-specific DNA-binding transcription factor activity in the nucleus.
ARATH	STM	IPR001356,IPR005539,IPR005540,IPR005541,IPR008422	GO:0003677	DNA binding	MODIFY	yes	GO:0000978 RNA polymerase II cis-regulatory region sequence-specific DNA binding	The existing term is true but less informative than GO:0000978 for STM's core DNA-binding activity.
ARATH	STM	IPR008422,IPR017970	GO:0006355	regulation of DNA-templated transcription	MODIFY	yes	GO:0006357 regulation of transcription by RNA polymerase II	Replace this broad BP term with GO:0006357, which is already present and better aligned with STM's RNA polymerase II transcription factor activity.
ARATH	STM	IPR005540,IPR005541	GO:0005634	nucleus	ACCEPT	no		Nucleus is the core active location for STM's transcription factor activity.
ARATH	SVP	IPR033896	GO:0000977	RNA polymerase II transcription regulatory region sequence-specific DNA binding	ACCEPT	no		Retain as a valid cis-regulatory DNA-binding molecular function, while relying on more specific RNA polymerase II transcription factor terms for the synthesized core function.
ARATH	SVP	IPR002100,IPR036879	GO:0003677	DNA binding	MODIFY	yes	GO:0000978 RNA polymerase II cis-regulatory region sequence-specific DNA binding	Replace the broad parent term with the more specific cis-regulatory region sequence-specific DNA-binding term supported by SVP biology.
ARATH	SVP	IPR002487	GO:0003700	DNA-binding transcription factor activity	MODIFY	yes	GO:0000981 DNA-binding transcription factor activity, RNA polymerase II-specific	Use the more specific RNA polymerase II-specific DNA-binding transcription factor activity term.
ARATH	SVP	IPR002100,IPR036879	GO:0046983	protein dimerization activity	MODIFY	yes	GO:0046982 protein heterodimerization activity	The broad dimerization term is directionally correct, but the local direct interaction evidence supports the more specific heterodimerization term for SVP complexes with MADS partners.
ARATH	SVP	IPR002487	GO:0006355	regulation of DNA-templated transcription	MODIFY	yes	GO:0006357 regulation of transcription by RNA polymerase II	Replace with GO:0006357, which better matches SVP's regulation of protein-coding floral regulator genes.
ARATH	SVP	IPR033896	GO:0045944	positive regulation of transcription by RNA polymerase II	MODIFY	yes	GO:0000122 negative regulation of transcription by RNA polymerase II	Replace the unsupported positive-regulation call with negative regulation of transcription by RNA polymerase II.
ARATH	SVP	IPR002487	GO:0005634	nucleus	ACCEPT	no		Retain; this is the expected cellular location for SVP's core transcriptional regulatory function.
ARATH	TOC1	IPR001789	GO:0000160	phosphorelay signal transduction system	REMOVE	yes		GO:0000160 is defined as a histidine-kinase autophosphorylation to aspartate phosphotransfer cascade. TOC1 lacks the catalytic Asp (Glu-71) and acts as a DNA-binding transcriptional repressor, not a phosphorelay component. This is an over-propagated electronic annotation from the family-level receiver-domain signature and is biologically incorrect for TOC1.
ARATH	TOC1	IPR045279	GO:0009736	cytokinin-activated signaling pathway	REMOVE	yes		GO:0009736 is the cytokinin two-component signaling cascade ending in transcription. TOC1 is not a cytokinin-signaling response regulator (those are the type-A/type-B ARRs); it lacks the catalytic Asp and there is no experimental evidence linking TOC1 to cytokinin signaling. This is an over-propagated electronic annotation from the receiver-domain family signature.
ARATH	TT8	IPR011598,IPR036638	GO:0046983	protein dimerization activity	ACCEPT	no		Dimerization is a conserved and functionally relevant property of bHLH transcription factors.
ARATH	WOX5	IPR001356	GO:0003677	DNA binding	MODIFY	yes	GO:0043565 sequence-specific DNA binding	The term is correct but too general for a sequence-specific homeodomain transcription factor. Replace with sequence-specific DNA binding, which is independently supported experimentally and by the WUS-type homeobox domain.
ARATH	WOX5	IPR044555	GO:0003700	DNA-binding transcription factor activity	ACCEPT	no		Correct molecular function for a WUS-type homeodomain transcription factor with demonstrated sequence-specific DNA binding and direct target gene regulation.
ARATH	WRI1	IPR001471,IPR036955	GO:0003700	DNA-binding transcription factor activity	ACCEPT	no		Correct core molecular function. WRI1 is a sequence-specific DNA-binding transcriptional activator; supported by ISS from family analysis below.
ARATH	WRI1	IPR001471,IPR036955	GO:0006355	regulation of DNA-templated transcription	ACCEPT	no		Correct core biological process, consistent with the IBA annotation and WRI1's transcriptional-activator role.
ARATH	WRKY70	IPR003657,IPR036576,IPR044810	GO:0003700	DNA-binding transcription factor activity	ACCEPT	no		DNA-binding transcription factor activity is the core molecular function of WRKY70.
ARATH	WRKY70	IPR003657,IPR036576	GO:0043565	sequence-specific DNA binding	ACCEPT	no		Sequence-specific DNA binding is a direct supported molecular function of WRKY70.
ARATH	WRKY70	IPR003657,IPR036576	GO:0006355	regulation of DNA-templated transcription	ACCEPT	no		Regulation of DNA-templated transcription is core to WRKY70 function, although the molecular function is better captured by DNA-binding transcription factor activity.
ARATH	WUS	IPR044555	GO:0003700	DNA-binding transcription factor activity	ACCEPT	no		This annotation accurately captures WUS's primary molecular function as a transcription factor. The protein contains a homeodomain for DNA binding and has been experimentally shown to regulate numerous target genes including CLV3, AG, and LEC1. Both activating and repressing activities are well-documented, making this a core function annotation.
AZOVI	nifA	IPR010113	GO:0003700	DNA-binding transcription factor activity	MODIFY	yes	GO:0001216 DNA-binding transcription activator activity	This annotation is correct but too general. NifA is specifically a sigma-54-dependent transcriptional activator, not just any DNA-binding transcription factor. The protein does bind DNA through its C-terminal HTH domain (494-513) and activates transcription, but GO:0001216 (DNA-binding transcription activator activity) would be more accurate as it specifies the activator function. Even better would be a term specific to bacterial-type RNA polymerase transcriptional activators working with sigma-54, though such a specific term may not exist.
AZOVI	nifA	IPR002078,IPR010113	GO:0006355	regulation of DNA-templated transcription	MODIFY	yes	GO:0045893 positive regulation of DNA-templated transcription	This biological process annotation is correct but could be more specific. NifA specifically performs positive regulation of transcription by RNA polymerase. The term GO:0045893 (positive regulation of DNA-templated transcription) would be more accurate as NifA is an activator, not a general regulator. However, this annotation is acceptable as a general biological process term.
AZOVI	nifA	IPR010113	GO:0009399	nitrogen fixation	MODIFY	yes	GO:0045893 positive regulation of DNA-templated transcription	"This biological process annotation needs refinement. While NifA is essential for nitrogen fixation (deletion mutants cannot grow diazotrophically), the protein itself does not perform nitrogen fixation - it regulates the expression of genes encoding nitrogenase and other proteins that actually fix nitrogen. GO has no ""regulation of nitrogen fixation"" term, so a ""positive regulation of nitrogen fixation"" term is requested under proposed_new_terms. NifA is a transcriptional regulator, not an enzyme that fixes nitrogen."
AZOVI	nifA	IPR002197	GO:0043565	sequence-specific DNA binding	ACCEPT	no		This molecular function annotation is correct and specific. NifA binds to specific DNA sequences at nif promoters through its C-terminal HTH DNA-binding domain (494-513). The protein recognizes conserved upstream activating sequences (UAS) located at -24/-12 promoter regions typical of sigma-54-dependent promoters. This sequence-specific DNA binding is essential for NifA to activate transcription of its target genes. This is a core molecular function.
BACAN	ermJ	IPR020596,IPR020598	GO:0000154	rRNA modification	ACCEPT	no		Erm enzymes confer resistance by methylating 23S rRNA; this process annotation is biologically appropriate.
BACFG	ermF	IPR020596,IPR020598	GO:0000154	rRNA modification	ACCEPT	no		Erm enzymes confer resistance by methylating 23S rRNA; this process annotation is biologically appropriate.
BACSP	knt	IPR012481	GO:0016779	nucleotidyltransferase activity	MODIFY	yes	GO:0034068 aminoglycoside nucleotidyltransferase activity	Replace the broad or over-specific electronic term 'nucleotidyltransferase activity' with aminoglycoside nucleotidyltransferase activity based on UniProt/CARD determinant identity and the curated ARO->GO mapping.
BACSP	knt	IPR012481	GO:0046677	response to antibiotic	ACCEPT	no		The CARD/ARO determinant identity supports an antibiotic-resistance biological role.
BACSU	amyE	IPR006048	GO:0003824	catalytic activity	MODIFY	yes	GO:0004556 alpha-amylase activity	While the annotation is technically correct, it is uninformative. AmyE has been biochemically characterized with specific activity measurements (~1,280 U/mg), crystal structure solved (PDB:1BAG, 1UA7), and catalytic residues identified (Asp217 nucleophile, Glu249 proton donor, Asp310 transition state stabilizer). The more specific term GO:0004556 (alpha-amylase activity) should be used instead.
BACSU	amyE	IPR006046,IPR006047,IPR006048	GO:0005975	carbohydrate metabolic process	MODIFY	yes	GO:0000272 polysaccharide catabolic process	While carbohydrate metabolic process is not incorrect, it is overly general for this well-characterized starch-degrading enzyme. AmyE specifically catalyzes starch hydrolysis, producing maltose and glucose. More specific terms would better represent the biological process: GO:0000272 (polysaccharide catabolic process) or GO:0009251 (glucan catabolic process) would be more informative.
BACSU	amyE	IPR006046,IPR006048	GO:0043169	cation binding	MODIFY	yes	GO:0005509 calcium ion binding	While AmyE does bind cations, specifically calcium ions (2 per subunit), the annotation should use the more specific term GO:0005509 (calcium ion binding). The crystal structure (PDB:1BAG) reveals specific calcium binding sites with coordinating residues identified by X-ray crystallography.
BACSU	fliK	IPR001635	GO:0009424	bacterial-type flagellum hook	MODIFY	yes	GO:0005737 cytoplasm; GO:0120102 bacterial-type flagellum secretion apparatus	FliK is not a structural component of the flagellar hook - the hook is built from FlgE protein. FliK is a cytoplasmic protein that is intermittently exported through the fT3SS during hook assembly to control hook length. While FliK transiently passes through the hook region during secretion, it does not permanently reside there. A more accurate CC annotation would be cytoplasm or the flagellar secretion apparatus. The InterPro domain annotation (IPR001635) correctly identifies FliK as a hook-length control protein, but the mapping to the hook CC term is inappropriate.
BACSU	fliK	IPR001635	GO:0044780	bacterial-type flagellum assembly	ACCEPT	no		FliK is a core regulator of flagellum assembly. It controls hook length and triggers the critical switch from rod/hook substrate export to filament substrate export. Loss of FliK results in polyhook formation and failure to assemble functional flagella. This annotation accurately captures FliK's essential role in the flagellar assembly process.
BACSU	fliY	IPR001172	GO:0003774	cytoskeletal motor activity	REMOVE	yes		"This is an over-annotation. FliY is a component of the flagellar motor switch complex (C-ring) but it does not have motor activity itself. The motor activity is generated by the stator units (MotA/MotB) interacting with FliG. FliY's role is to modulate CheY-P levels, not to generate rotational force. The InterPro domain hit is based on FliN homology, but FliN is a switch component, not a motor per se. The term ""cytoskeletal motor activity"" implies direct force generation, which FliY does not perform."
BACSU	fliY	IPR012826	GO:0009288	bacterial-type flagellum	MODIFY	yes	GO:0009433 bacterial-type flagellum basal body, C ring	FliY localizes specifically to the C-ring of the flagellar basal body, not throughout the flagellum generally. A more specific annotation to the C-ring would be more informative and accurate.
BACSU	fliY	IPR001172	GO:0009425	bacterial-type flagellum basal body	MODIFY	yes	GO:0009433 bacterial-type flagellum basal body, C ring	FliY is specifically a component of the C-ring within the basal body. While GO:0009425 is not incorrect, GO:0009433 (C-ring) would be more precise and informative.
BACSU	fliY	IPR012826	GO:0016020	membrane	MODIFY	yes	GO:0009433 bacterial-type flagellum basal body, C ring	This annotation is not wrong but is uninformative. FliY is a peripheral membrane protein that specifically localizes to the flagellar C-ring. The more specific term should be used.
BACSU	fliY	IPR001172,IPR012826	GO:0071973	bacterial-type flagellum-dependent cell motility	KEEP_AS_NON_CORE	yes		FliY is involved in flagellum-dependent motility as a component of the motor switch, but this is not its primary molecular function. Its core function is as a CheY-P phosphatase that regulates motility. This annotation reflects a downstream consequence of its biochemical activity rather than a direct role.
BACSU	lipA	IPR006638,IPR007197	GO:0003824	catalytic activity	MODIFY	yes	GO:0016992 lipoate synthase activity	"LipA has well-established lipoyl synthase activity (EC 2.8.1.8). The term ""catalytic activity"" is overly broad and should be replaced with the specific molecular function term GO:0016992 (lipoate synthase activity) which accurately describes LipA's enzymatic function."
BACSU	minC	IPR005526,IPR036145	GO:0000902	cell morphogenesis	KEEP_AS_NON_CORE	yes		The term cell morphogenesis is broader than MinC's actual function. MinC's primary role is in division site selection/FtsZ inhibition. The morphological phenotypes observed in minC mutants (elongation, minicells) are secondary consequences of aberrant division. This annotation is not wrong but represents a non-core, indirect effect. The IEA source (InterPro) likely infers this from the MinC domain family rather than specific experimental evidence for morphogenesis function.
BACSU	minC	IPR013033	GO:1901891	regulation of cell septum assembly	ACCEPT	no		"This is an appropriate annotation for MinC. The term ""regulation of cell septum assembly"" correctly indicates that MinC modulates where and when septa form without implying direct positive involvement in septum construction. MinC prevents septum formation at poles through FtsZ inhibition, which is regulatory."
BACSU	minD	IPR010223	GO:0016887	ATP hydrolysis activity	ACCEPT	no		This is a duplicate annotation with the same GO term (GO:0016887) as the IBA annotation but with IEA evidence from InterPro (IPR010223 MinD domain). Duplicates with different evidence sources are acceptable. ATP hydrolysis activity is well-established for MinD.
BACSU	nprE	IPR001570,IPR013856,IPR023612	GO:0004222	metalloendopeptidase activity	ACCEPT	no		This is the most specific and accurate molecular function term for NprE. The enzyme is a zinc-dependent metalloendopeptidase that hydrolyzes internal peptide bonds using a catalytic mechanism involving Zn2+-activated water. The HExxH motif characteristic of M4 metalloproteases is present, and the catalytic mechanism is well-established for this enzyme family.
BACSU	sacB	IPR003469	GO:0009758	carbohydrate utilization	MODIFY	yes	GO:0010146 fructan biosynthetic process	"The term ""carbohydrate utilization"" (GO:0009758) implies catabolism for energy or nutrient acquisition. While SacB does use sucrose as a substrate, its primary biological function is levan biosynthesis - an anabolic process producing extracellular polysaccharide. A more accurate biological process term would be GO:0010146 ""fructan biosynthetic process"" since levan is a type of fructan (beta-2,6-linked fructose polymer)."
BACSU	secA	IPR000185,IPR020937	GO:0006886	intracellular protein transport	ACCEPT	no		"This annotation is accurate but very general. SecA does participate in intracellular protein transport as part of the Sec pathway. The more specific annotation ""protein transport by the Sec complex"" (GO:0043952) better captures the specificity of SecA function, but this broader term is not incorrect."
BACSU	secA	IPR011115,IPR011116,IPR011130,IPR020937,IPR036670	GO:0016020	membrane	ACCEPT	no		This general membrane annotation is technically correct but less informative than the specific plasma membrane annotations. It can be retained as complementary evidence from InterPro.
BACSU	secA	IPR011115,IPR011116,IPR011130,IPR036670	GO:0017038	protein import	REMOVE	yes		"SecA is a protein EXPORTER, not importer. The Sec translocase moves preproteins from the cytoplasm out through the membrane. ""Protein import"" implies movement into the cytoplasm, which is the opposite of SecA's function. This annotation should be removed as it is misleading."
BACSU	sigE	IPR000943,IPR007627,IPR007630,IPR013325,IPR014200,IPR014284	GO:0003700	DNA-binding transcription factor activity	MODIFY	yes	GO:0016987 sigma factor activity	The term GO:0003700 is designed for classical transcription factors that independently bind DNA regulatory elements and activate or repress transcription. Sigma factors have a distinct mechanism - they are subunits of the RNAP holoenzyme that confer promoter specificity and enable transcription initiation. The more appropriate and specific term is GO:0016987 (sigma factor activity), which is already annotated. This IEA annotation from InterPro mapping conflates sigma factors with classical transcription factors.
BACSU	sigE	IPR000943,IPR007627,IPR007630,IPR013325,IPR014200,IPR014284	GO:0006352	DNA-templated transcription initiation	ACCEPT	no		"This annotation is highly appropriate for SigE. Sigma factors function specifically at the transcription initiation step - they enable promoter recognition and open complex formation but are released during the transition to elongation. UniProt explicitly states that sigma factors are ""initiation factors"" that are ""then released"" after promoting attachment to initiation sites. This term accurately captures the specific stage of transcription where sigma factors act."
BACSU	sigF	IPR000943,IPR007624,IPR007627,IPR007630,IPR013325,IPR014236,IPR014284,IPR014322	GO:0003700	DNA-binding transcription factor activity	MODIFY	yes	GO:0016987 sigma factor activity	The term GO:0003700 is designed for classical transcription factors that independently bind DNA regulatory elements. Sigma factors have a distinct mechanism - they are subunits of the RNAP holoenzyme that confer promoter specificity. The more appropriate and specific term is GO:0016987 (sigma factor activity), which is already annotated. This IEA annotation from InterPro mapping may be overly broad.
BACSU	sigF	IPR000943,IPR007624,IPR007627,IPR007630,IPR013325,IPR014236,IPR014284,IPR014322	GO:0006352	DNA-templated transcription initiation	ACCEPT	no		This annotation is highly appropriate for SigF. Sigma factors function specifically at the transcription initiation step - they enable promoter recognition and open complex formation but are released during the transition to elongation. This term accurately captures the specific stage of transcription where sigma factors act.
BACSU	sigG	IPR000943,IPR007624,IPR007627,IPR007630,IPR013325,IPR014212,IPR014284,IPR014322	GO:0003700	DNA-binding transcription factor activity	MODIFY	yes	GO:0016987 sigma factor activity	GO:0003700 is defined as sequence-specific DNA binding that modulates transcription. Sigma factors function differently: they are dissociable subunits of RNA polymerase that determine promoter recognition. The correct term is GO:0016987 sigma factor activity. While both involve promoter recognition, sigma factors act as part of the polymerase holoenzyme rather than as independent transcription factors.
BACSU	sigG	IPR000943,IPR007624,IPR007627,IPR007630,IPR013325,IPR014212,IPR014284,IPR014322	GO:0006352	DNA-templated transcription initiation	ACCEPT	no		"UniProt states that ""Sigma factors are initiation factors that promote the attachment of RNA polymerase to specific initiation sites and are then released."" The specific role of sigma factors in initiation (as opposed to elongation or termination) makes this a precise and accurate annotation."
BACSU	sigK	IPR000943,IPR007627,IPR007630,IPR013325,IPR014284	GO:0003700	DNA-binding transcription factor activity	MODIFY	yes	GO:0016987 sigma factor activity	GO:0003700 is defined as sequence-specific DNA binding that modulates transcription, applicable to classical transcription factors that independently bind DNA regulatory elements. Sigma factors function differently: they are dissociable subunits of RNA polymerase that determine promoter recognition as part of the holoenzyme complex. The correct term is GO:0016987 sigma factor activity, which is already annotated for sigK.
BACSU	sigK	IPR000943,IPR007627,IPR007630,IPR013325,IPR014284	GO:0006352	DNA-templated transcription initiation	ACCEPT	no		"UniProt states that ""Sigma factors are initiation factors that promote the attachment of RNA polymerase to specific initiation sites and are then released."" The specific role of sigma factors in initiation (as opposed to elongation or termination) makes this a precise and accurate annotation for sigK."
BACSU	spo0A	IPR014879	GO:0003700	DNA-binding transcription factor activity	ACCEPT	no		"This is a core molecular function of Spo0A. UniProt describes it as ""Repressor of abrB, activator of the spoIIa operon"" (UniProt P06534). The protein has a well-characterized HTH DNA-binding domain and regulates transcription of hundreds of genes involved in sporulation, biofilm formation, and stationary phase physiology."
BACSU	spo0A	IPR012052,IPR014879	GO:0005509	calcium ion binding	KEEP_AS_NON_CORE	yes		"While UniProt notes ""Binds 1 Ca(2+) ion per subunit"" based on similarity evidence, this appears to be a structural feature common to CheY-like receiver domains rather than a functionally characterized calcium-binding activity specific to Spo0A function. The primary function involves phosphorylation at Asp-56, not calcium-dependent regulation. The annotation is kept as non-core since calcium binding may provide structural stability but is not central to Spo0A's role as a transcription factor."
BACSU	spo0A	IPR014879	GO:0042173	regulation of sporulation resulting in formation of a cellular spore	ACCEPT	no		"This accurately captures Spo0A's role as a master regulator of sporulation. The deep research explains that ""Distinct Spo0A~P thresholds produce graded outputs: low/moderate Spo0A~P -> biofilm/competence pathways; high Spo0A~P -> commitment to sporulation"" (mSystems, 2025). Spo0A regulates rather than merely participates in sporulation."
BACSU	spo0A	IPR012052	GO:0043937	regulation of sporulation	ACCEPT	no		While GO:0042173 is more specific and already annotated, keeping this broader term is acceptable as it accurately describes Spo0A function. IEA annotations at different specificity levels are common and provide useful redundancy.
BACSU	spo0A	IPR012052	GO:0051606	detection of stimulus	REMOVE	yes		This annotation is inappropriate for Spo0A. Response regulators like Spo0A do not directly detect stimuli; they receive signals from sensor histidine kinases. The upstream kinases (KinA, KinB, etc.) are the actual stimulus detectors. Spo0A is the effector component that responds to phosphorylation by the phosphorelay, not a sensor. This is an over-annotation based on the general response regulator domain classification.
BACSU	spoIIAA	IPR003658,IPR014237	GO:0006355	regulation of DNA-templated transcription	MARK_AS_OVER_ANNOTATED	yes		This term is too general and redundant with the more specific positive regulation of transcription. SpoIIAA acts via sigma-factor control rather than serving as a direct transcriptional regulator, so this generic term overstates its role.
BACSU	spoIIAA	IPR003658	GO:0043856	anti-sigma factor antagonist activity	ACCEPT	no		The InterPro-based IEA aligns with the experimentally supported function of SpoIIAA as an anti-anti-sigma factor in the sigma F pathway, which is core to its molecular role.
BACSU	spoIIAA	IPR014237	GO:0045152	antisigma factor binding	ACCEPT	no		Antisigma factor binding is consistent with SpoIIAA's anti-anti-sigma role and is supported by UniProt functional annotation describing SpoIIAB antagonism. The term is specific and appropriate for this molecular function.
BACSU	spoIIAB	IPR010194	GO:0016989	sigma factor antagonist activity	ACCEPT	no		The InterPro-based inference aligns with SpoIIAB's known anti-sigma factor role and is supported by UniProt functional annotation.
BACSU	spoIIAB	IPR010194	GO:0042174	negative regulation of sporulation resulting in formation of a cellular spore	MARK_AS_OVER_ANNOTATED	yes		SpoIIAB is required for proper timing of sigma F activity and sporulation, not for inhibiting sporulation overall. The term overstates its effect on the overall sporulation outcome.
BACSU	spoIIAB	IPR010194	GO:0045892	negative regulation of DNA-templated transcription	ACCEPT	no		SpoIIAB directly binds sigma F and blocks RNA polymerase holoenzyme formation, which is a direct negative regulatory effect on transcription.
BACSU	spoIIB	IPR007730,IPR036680	GO:0042834	peptidoglycan binding	ACCEPT	no		The SPOR-like domain is associated with peptidoglycan binding, and SpoIIB facilitates dissolution of septal peptidoglycan during engulfment.
BACSU	spoIIGA	IPR005081	GO:0030436	asexual sporulation	MODIFY	yes	GO:0034301 endospore formation	While 'asexual sporulation' is correct, 'endospore formation' (GO:0034301) is more specific and appropriate for the bacterial context. Endospore formation is the relevant biological process in Bacillus subtilis.
BACSU	spoVAD	IPR016039	GO:0016746	acyltransferase activity	REMOVE	yes		SpoVAD is NOT an acyltransferase. The thiolase-like fold has been evolutionarily repurposed for a structural role in the Ca-DPA transport complex. Recent literature (Zhang et al. 2025 J Bacteriol, Gao et al. 2024 Genes & Dev, Eichenberger 2024) consistently describe SpoVAD as a channel regulator, not an enzyme. The TCDB database classifies SpoVAD under the dipicolinic acid transporter family (9.A.11.1.1), not as an enzyme. This annotation represents a classic case of structural fold similarity being incorrectly used to infer enzymatic function.
BACSU	spoVD	IPR001460,IPR005311,IPR036138	GO:0008658	penicillin binding	ACCEPT	no		Duplicate of the IBA annotation for penicillin binding. Both are correct - SpoVD is a penicillin-binding protein. The IEA from InterPro domain mapping provides independent computational support. Duplicates with different evidence sources are acceptable.
BALMU	A0A8B8WEG2	IPR008271	GO:0004672	protein kinase activity	MARK_AS_OVER_ANNOTATED	yes		The term is correct but too general. The specific CDK Ser/Thr kinase activity term (GO:0004693) captures the function more precisely and is already present.
BOVIN	E1BL04	IPR012510,IPR030072	GO:0030036	actin cytoskeleton organization	MARK_AS_OVER_ANNOTATED	yes		GO:0030036 is a broader parent of GO:0007015 (actin filament organization) which is already annotated. The more specific term better captures XIRP2's role in organizing actin filaments within the sarcomere.
BOVIN	E1BL04	IPR012510	GO:0030054	cell junction	MARK_AS_OVER_ANNOTATED	yes		GO:0030054 is a broad parent term. The more specific GO:0005911 (cell-cell junction) already present in the annotation set, and even more specific terms such as intercalated disc (GO:0014704) would better capture the known localization.
BPT4	10	IPR008987	GO:0019076	viral release from host cell	PENDING	no		TODO: Review this GOA annotation
BPT4	12	IPR027448	GO:0046872	metal ion binding	PENDING	no		TODO: Review this GOA annotation
BPT4	19	IPR010667	GO:0005198	structural molecule activity	PENDING	no		TODO: Review this GOA annotation
BPT4	37	IPR005003	GO:0005198	structural molecule activity	PENDING	no		TODO: Review this GOA annotation
BPT4	41	IPR046393	GO:0039686	bidirectional double-stranded viral DNA replication	PENDING	no		TODO: Review this GOA annotation
BPT4	46	IPR038729	GO:0006302	double-strand break repair	PENDING	no		TODO: Review this GOA annotation
BPT4	46	IPR038729	GO:0016887	ATP hydrolysis activity	PENDING	no		TODO: Review this GOA annotation
BPT4	5	IPR001165,IPR002196	GO:0016998	cell wall macromolecule catabolic process	PENDING	no		TODO: Review this GOA annotation
BPT4	9	IPR008987	GO:0019076	viral release from host cell	PENDING	no		TODO: Review this GOA annotation
BPT4	DAM	IPR002052	GO:0003676	nucleic acid binding	MODIFY	yes	GO:0043565 sequence-specific DNA binding	This term is too general. The protein specifically binds DNA (not RNA) in a sequence-specific manner (GATC recognition). More specific terms like GO:0003677 (DNA binding) or GO:0043565 (sequence-specific DNA binding) are more informative and are already annotated.
BPT4	DAM	IPR012263,IPR012327	GO:0009307	DNA restriction-modification system	MODIFY	yes	GO:0099018 symbiont-mediated evasion of host restriction-modification system	This term implies Dam is part of a complete restriction-modification system with both restriction and modification activities. T4 Dam is explicitly an orphan methyltransferase (M.EcoT4Dam) that provides DNA protection without an associated restriction enzyme. The appropriate term is GO:0099018 (symbiont-mediated evasion of host restriction-modification system) which accurately describes the protective role against host R-M systems.
BPT4	E	IPR001165,IPR002196	GO:0016998	cell wall macromolecule catabolic process	KEEP_AS_NON_CORE	yes		Correct parent term from InterPro mapping. The enzyme catabolizes peptidoglycan, which is the major structural component of bacterial cell walls. This is slightly less specific than GO:0009253 (peptidoglycan catabolic process), so it should be kept as a non-core parent rather than the main biological-process annotation.
BPT4	stp	IPR012585	GO:0004518	nuclease activity	PENDING	no		TODO: Review this GOA annotation
BPT4	stp	IPR012585	GO:0050792	regulation of viral process	PENDING	no		TODO: Review this GOA annotation
BPT4	t	IPR020982	GO:0044659	viral release from host cell by cytolysis	PENDING	no		TODO: Review this GOA annotation
BRADI	BRADI_1g66227v3	IPR044516	GO:0042732	D-xylose metabolic process	KEEP_AS_NON_CORE	yes		The reaction produces UDP-xylose, so D-xylose metabolism is not wrong. The annotation is less informative than the direct UDP-D-xylose biosynthetic process term.
BRADI	BRADI_1g66227v3	IPR044516	GO:0070403	NAD+ binding	ACCEPT	no		This duplicate NAD+ binding annotation agrees with the IBA row and with the enzyme mechanism; it is retained because the catalytic function is explicitly NAD-dependent.
BRADI	LOC100829928	IPR008948	GO:0003824	catalytic activity	MARK_AS_OVER_ANNOTATED	yes		The protein is not merely a generic catalyst: UniProt assigns EC 4.3.1.24, the InterPro signatures include a phenylalanine ammonia-lyase-specific family, and the review already contains the specific GO:0045548 molecular function.
BRADI	LOC100829928	IPR005922	GO:0006559	L-phenylalanine catabolic process	KEEP_AS_NON_CORE	yes		The catalytic reaction deaminates L-phenylalanine, so the catabolic process term is mechanistically true. It is less central than the product pathway terms because this enzyme is best understood as the entry step to trans-cinnamate and phenylpropanoid biosynthesis.
BRADI	LOC100829928	IPR005922,IPR022313	GO:0016841	ammonia-lyase activity	KEEP_AS_NON_CORE	yes		Ammonia-lyase activity is a valid parent for PAL/HAL-family enzymes, but the InterPro Phe_NH3-lyase signature and EC 4.3.1.24 support the more precise phenylalanine ammonia-lyase activity term.
BURCH	A0B297	IPR003439,IPR017871	GO:0016887	ATP hydrolysis activity	ACCEPT	no		ATP hydrolysis is the core catalytic activity of this protein, converting the chemical energy of ATP into mechanical work for substrate transport. The UniProt record lists EC numbers 7.5.2.11 and 7.5.2.7, both of which involve ATP hydrolysis coupled to carbohydrate transport. This is an essential molecular function annotation.
CALMI	A0A4W3GVU1	IPR035979,IPR036397	GO:0003676	nucleic acid binding	MODIFY	yes	GO:0003729 mRNA binding	The term is too general. ESRP1 binds RNA, not DNA. The InterPro domains (RBD superfamily, RRM domain) that generated this annotation are RNA-binding domains, and the more precise GO:0003723 (RNA binding) is already present. An even more specific term such as GO:0003729 (mRNA binding) would better reflect ESRP1's function as a pre-mRNA splicing regulator.
CALMI	A0A4W3GVU1		GO:0048024	regulation of mRNA splicing, via spliceosome	NEW	no		ESRP1 is a splicing regulator and this process term directly reflects its core biological role. The UniProt entry lists mRNA processing and mRNA splicing as keywords, and the deep research literature extensively documents ESRP1's function in regulating alternative splicing via the spliceosome.
CANAL	CDC37	IPR013855	GO:0019901	protein kinase binding	ACCEPT	no		Protein kinase binding is a defining function of CDC37. PMID:15013782 demonstrates interaction with the Crk1 kinase domain. The InterPro domain IPR013855 directly corresponds to the kinase-binding N-terminal domain of CDC37.
HYPJE	IRE1	IPR010513	GO:0004540	RNA nuclease activity	ACCEPT	no		Correct but less specific than GO:0004521. Acceptable as a broad IEA.
HYPJE	IRE1	IPR000719,IPR008271	GO:0004672	protein kinase activity	ACCEPT	no		Correct but less specific than GO:0004674. Acceptable as an IEA. Consistent with IDA evidence (PMID:15480788).
HYPJE	IRE1	IPR010513	GO:0006397	mRNA processing	ACCEPT	no		Correct. IRE1 endoribonuclease activity directly processes HAC1 pre-mRNA. Confirmed by observation of HAC1 mRNA splicing upon ire1 overexpression (PMID:15480788).
HYPJE	IRE1	IPR045133	GO:0030968	endoplasmic reticulum unfolded protein response	ACCEPT	no		Correct. This is the core biological process of IRE1. Confirmed by functional studies showing UPR target gene upregulation (PMID:15480788).
CHICK	GLDC	IPR001597	GO:0006520	amino acid metabolic process	MARK_AS_OVER_ANNOTATED	yes		This term is too general for GLDC. The more specific terms GO:0006544 (glycine metabolic process) and GO:0006546 (glycine catabolic process) are already annotated and more informative. The IEA from InterPro is not wrong but provides minimal information beyond what more specific terms convey.
CHICK	GLDC	IPR003437	GO:0006544	glycine metabolic process	MARK_AS_OVER_ANNOTATED	yes		GLDC specifically catabolizes glycine; it does not synthesize it. The term GO:0006546 (glycine catabolic process) is more specific and accurately describes GLDC function. This parent term adds little beyond what the catabolic child term provides. Better represented by GO:0019464.
CHICK	GLDC	IPR020581	GO:0006546	glycine catabolic process	ACCEPT	no		GLDC is indeed involved in glycine catabolic process. The IEA correctly identifies this role. While GO:0019464 (glycine decarboxylation via glycine cleavage system) is more specific, this term accurately describes GLDC's role in glycine breakdown.
CHICK	GLDC	IPR001597	GO:0016829	lyase activity	MARK_AS_OVER_ANNOTATED	yes		While GLDC does catalyze a decarboxylation (lyase-type) reaction, the specific term GO:0004375 already captures this. The InterPro-based IEA correctly identifies the broad enzymatic class but provides minimal informative value beyond what more specific terms convey.
CHLRE	psaC	IPR017491	GO:0009522	photosystem I	ACCEPT	no		Correct cellular component (complex) annotation. PsaC is an extrinsic stromal subunit of PSI; it is resolved as chain C in numerous Chlamydomonas PSI cryo-EM structures, and its inactivation destabilizes the whole PSI complex. The InterPro2GO mapping (IPR017491, PSI PsaC) is accurate.
CHLRE	psaC	IPR017491	GO:0009773	photosynthetic electron transport in photosystem I	ACCEPT	no		"This is the correct and appropriately specific biological process term. PsaC carries the FA/FB part of the PSI electron transfer chain; experimental mutagenesis in Chlamydomonas directly demonstrated its role in photosynthetic electron transport to ferredoxin. The InterPro2GO mapping is accurate and more informative than the parent term ""photosynthesis""."
CHLRE	psaC	IPR017491	GO:0042651	thylakoid membrane	MARK_AS_OVER_ANNOTATED	yes		"PsaC is in the thylakoid membrane, so the term is accurate, but it is less specific than GO:0009535 ""chloroplast thylakoid membrane"", which is already annotated and is appropriate for this chloroplast-encoded alga protein. The generic term adds no information beyond the specific one; mark as over-annotated in favor of the chloroplast-specific term."
CHLRE	psaC	IPR017491	GO:0051539	4 iron, 4 sulfur cluster binding	ACCEPT	no		"This is the correct and appropriately specific molecular function term for cofactor binding by PsaC. UniProt documents binding of two [4Fe-4S] clusters with eight cysteine BINDING-site residues, and experimental work in Chlamydomonas characterized clusters FA and FB coordinated by PsaC. This precise term supersedes the retired, broader SPKW term ""metal ion binding""."
CHRVO	Q7NUH2	IPR000835,IPR039422	GO:0003700	DNA-binding transcription factor activity	ACCEPT	no		DNA-binding transcription factor activity is the primary molecular function of MarR family proteins. The InterPro domain assignments IPR000835 and IPR039422 strongly support this annotation. This represents the most informative molecular function annotation for this protein.
CLOCL	P38058	IPR001956,IPR036966	GO:0005975	carbohydrate metabolic process	MARK_AS_OVER_ANNOTATED	yes		CbpA is non-catalytic. It facilitates carbohydrate metabolism by organizing catalytic enzymes, but does not itself perform any metabolic reaction.
CLOCL	P38058	IPR002102,IPR008965	GO:0030246	carbohydrate binding	ACCEPT	no		The CBM3 domain mediates carbohydrate binding. This is a true positive but could be made more specific with GO:0030248.
CLOCL	P38058	IPR001956,IPR036966	GO:0030248	cellulose binding	ACCEPT	no		Cellulose binding via CBM3 is a well-characterized function of CbpA, demonstrated experimentally. This is essential for targeting the cellulosome to substrate.
CLOCL	Q6DTY2	IPR001701	GO:0004553	hydrolase activity, hydrolyzing O-glycosyl compounds	KEEP_AS_NON_CORE	yes		This is a true parent term of the more specific cellulase activity. It's correct but not the most informative annotation for this enzyme.
CLOCL	Q6DTY2	IPR001701,IPR004197,IPR008928,IPR012341	GO:0005975	carbohydrate metabolic process	MARK_AS_OVER_ANNOTATED	yes		This parent term is overly broad. GO:0030245 (cellulose catabolic process) is the appropriate specific term for EngO function.
CLOCL	Q6DTY2	IPR004197	GO:0008810	cellulase activity	ACCEPT	no		EngO is a GH9 family endoglucanase with demonstrated cellulase activity. This is the appropriate molecular function annotation.
CLOCL	Q9RGE6	IPR001701,IPR008928,IPR012341	GO:0005975	carbohydrate metabolic process	MARK_AS_OVER_ANNOTATED	yes		This parent term is overly broad. GO:0030245 (cellulose catabolic process) is the appropriate specific term for EngL function.
CLOCL	Q9RGE7	IPR002102	GO:0000272	polysaccharide catabolic process	REMOVE	yes		HbpA has no catalytic domain. It is a structural/organizational protein that recruits enzymes via its cohesin domain but does not directly participate in polysaccharide breakdown.
CLOCL	Q9RGE7	IPR002102,IPR008965	GO:0030246	carbohydrate binding	UNDECIDED	yes		The CBM annotation is inconsistent with experimental literature which describes HbpA as having cohesin and SLH-like domains. Until direct carbohydrate binding is validated, this annotation should be treated with caution.
CLOCL	Q9RGE8	IPR001701,IPR004197,IPR008928,IPR012341	GO:0005975	carbohydrate metabolic process	MARK_AS_OVER_ANNOTATED	yes		This parent term is overly broad. GO:0030245 (cellulose catabolic process) is the appropriate specific term for EngK function.
CLOCL	Q9RGE8	IPR004197	GO:0008810	cellulase activity	ACCEPT	no		EngK is a GH9 family cellulase with demonstrated endo-1,4-β-glucanase activity. This is the appropriate molecular function annotation.
CLODI	hadA	IPR003673	GO:0003824	catalytic activity	MODIFY	yes	GO:0043712 2-hydroxyisocaproate CoA-transferase activity	"GO:0003824 (catalytic activity) is the root molecular function term and provides no information beyond ""this protein is an enzyme."" HadA's reaction has been directly demonstrated biochemically by Kim et al. (PMID:16957230), who showed CoA-transferase activity with (R)-2-hydroxyisocaproyl-CoA as donor and isocaproate or (E)-2-isocaprenoate as acceptor, with substrate specificity confirmed by lack of activity with acetyl-CoA or butyryl-CoA. The matching specific term GO:0043712 (2-hydroxyisocaproate CoA-transferase activity) corresponds exactly to the UniProt RecName and EC 2.8.3.24 reaction."
COLLI	A0A2I0M3K7	IPR020103,IPR039048	GO:0001522	pseudouridine synthesis	MODIFY	yes	GO:0070902 mitochondrial tRNA pseudouridine synthesis	The general term is accurate but too broad. TRUB2 is specifically a mitochondrial pseudouridine synthase; GO:0070902 (mitochondrial tRNA pseudouridine synthesis) is the appropriate specific process based on mammalian ortholog evidence.
COLLI	A0A2I0M3K7	IPR020103	GO:0003723	RNA binding	KEEP_AS_NON_CORE	yes		RNA binding is an inherent mechanistic property of this RNA-modifying enzyme, not a distinct core function. It is accurate but uninformative beyond the primary catalytic annotation.
COLLI	A0A2I0M3K7	IPR002501	GO:0006396	RNA processing	MARK_AS_OVER_ANNOTATED	yes		Too broad. GO:0009451 (RNA modification), which is already annotated, is the correct parent-level process term. RNA processing implies a wider range of activities than what TRUB2 performs.
COLLI	A0A2I0M3K7	IPR020103	GO:0009451	RNA modification	KEEP_AS_NON_CORE	yes		Accurate parent-level process term, but redundant given the more specific pseudouridine synthesis annotation. Kept as non-core since it adds no specificity beyond the more informative annotations.
COLLI	A0A2I0M3K7	IPR020103,IPR039048	GO:0009982	pseudouridine synthase activity	MODIFY	yes	GO:0160148 tRNA pseudouridine(55) synthase activity	The general pseudouridine synthase activity term is accurate but too broad. Based on mammalian ortholog evidence, TRUB2 specifically catalyzes tRNA pseudouridine-55 formation; GO:0160148 (tRNA pseudouridine(55) synthase activity) captures this specificity. The ProtNLM2 prediction review also noted that GO:0106029 (tRNA pseudouridine synthase activity) is a more specific correct term.
COTJA	A0A8C2TBA7	IPR000720,IPR008977	GO:0003824	catalytic activity	MARK_AS_OVER_ANNOTATED	yes		GO:0003824 (catalytic activity) is a root-level MF term that provides no information beyond what is already captured by the more specific annotations GO:0004504 (peptidylglycine monooxygenase activity), GO:0004598 (peptidylamidoglycolate lyase activity), and GO:0016715 (oxidoreductase activity with ascorbate as donor). The InterPro-based annotation from IPR000720 and IPR008977 domains correctly identifies PAM as catalytically active, but the specific activity terms are far more informative.
COTJA	A0A8C2TBA7	IPR000323,IPR036939	GO:0004497	monooxygenase activity	KEEP_AS_NON_CORE	yes		The PHM domain of PAM is indeed a monooxygenase, so this annotation is technically correct. However, GO:0004504 (peptidylglycine monooxygenase activity) is a child term of GO:0004497 and provides more precise functional information. The InterPro-based annotation from Cu2_ascorb_mOase domains (IPR000323, IPR036939) is appropriate but redundant with the more specific term. Retaining as non-core since the specific term is already present.
COTJA	A0A8C2TBA7	IPR000323,IPR036939	GO:0005507	copper ion binding	ACCEPT	no		"The UniProt entry documents six copper binding residues in the PHM domain (positions 103, 104, 168, 238, 240, 310), all annotated as catalytic copper. The deep research confirms ""two copper atoms per PHM domain"" are required for the monooxygenase reaction. The InterPro domains IPR000323 and IPR036939 (Cu2_ascorb_mOase) correctly identify this copper-dependent activity. Copper binding is integral to PAM's core catalytic mechanism."
COTJA	A0A8C2TBA7	IPR000720	GO:0006518	peptide metabolic process	KEEP_AS_NON_CORE	yes		PAM is indeed involved in peptide metabolism through its role in C-terminal amidation. However, GO:0006518 is a very general parent term that does not convey the specific biological role of PAM. The InterPro-based annotation from IPR000720 (PHM/PAL) is technically correct but redundant with the more specific GO:0001519 (peptide amidation) annotation. Retaining as non-core since it adds no information beyond what the specific term provides.
COTJA	A0A8C2TBA7	IPR000720	GO:0016020	membrane	KEEP_AS_NON_CORE	yes		The UniProt entry documents a transmembrane helix at residues 734-758 and PAM is annotated as a single-pass membrane protein. The InterPro-based annotation from IPR000720 correctly identifies PAM as membrane-associated. However, GO:0016020 (membrane) is extremely broad. The more specific term GO:0030658 (transport vesicle membrane) is already annotated and provides better functional context. The primary sites of PAM activity are secretory granule membranes and the trans-Golgi network membrane.
COTJA	A0A8C2TBA7	IPR000323,IPR014783,IPR014784,IPR020611,IPR036939	GO:0016715	oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, reduced ascorbate as one donor, and incorporation of one atom of oxygen	KEEP_AS_NON_CORE	yes		GO:0016715 describes the reaction mechanism of the PHM domain at a chemical level, specifying that it uses reduced ascorbate as a paired donor for oxygen incorporation. This is technically accurate and well-supported by multiple InterPro domains (IPR000323, IPR014783, IPR014784, IPR020611, IPR036939). However, the more specific child term GO:0004504 (peptidylglycine monooxygenase activity) is already annotated and provides substrate-level specificity. Retaining as non-core since the specific term is present and more informative.
CRIGR	HSPH1	IPR013126	GO:0016887	ATP hydrolysis activity	MARK_AS_OVER_ANNOTATED	yes		Hsp110 family members have significantly reduced ATPase activity compared to canonical Hsp70 proteins. The InterPro family IPR013126 covers the entire Hsp70 superfamily, and while the domain architecture is conserved, Hsp110 members have diverged to function primarily as holdases and NEFs rather than as ATPases. Annotating HSPH1 with GO:0016887 (ATP hydrolysis activity) overstates its catalytic function. The core molecular functions are holdase chaperone activity and NEF activity (GO:0000774).
CUPNH	glcE	IPR016166	GO:0071949	FAD binding	REMOVE	yes		This annotation is redundant with GO:0050660 which covers the same FAD binding function. GO:0050660 (flavin adenine dinucleotide binding) is the more complete and descriptive term and should be retained instead
CUPNH	glcE	IPR016164	GO:0003824	catalytic activity	REMOVE	yes		The term 'catalytic activity' is too general and uninformative. The specific molecular function 'glycolate dehydrogenase activity' (GO:0019154) already captures the precise catalytic function of glcE
CUPNH	glcE	IPR006094,IPR016164,IPR036318	GO:0050660	flavin adenine dinucleotide binding	ACCEPT	no		FAD binding is an essential molecular function for glycolate dehydrogenase subunits. This annotation is well-supported by domain analysis and is functionally consistent with the oxidative decarboxylation mechanism
CUPNH	norR1	IPR002078	GO:0005524	ATP binding	MODIFY	yes	GO:0016887 ATP hydrolysis activity	The InterPro support identifies the sigma-54 interaction ATP-binding region, and NorR-family studies show that NO sensing stimulates NorR ATPase activity to activate transcription. Replace the generic binding term with ATP hydrolysis activity when making a positive MF assertion.
CUPNH	norR1	IPR002078	GO:0006355	regulation of DNA-templated transcription	MODIFY	yes	GO:0045893 positive regulation of DNA-templated transcription	The existing term is correct but too general. Species-specific Ralstonia evidence shows NorR is required for transcriptional activation of norA1/ norB1 in response to NO, and promoter-site mutations strongly reduce activation.
CUPNH	norR1	IPR002197	GO:0043565	sequence-specific DNA binding	MODIFY	yes	GO:0141097 ligand-modulated transcription activator activity	NorR is an NO-responsive, sigma-54-dependent transcriptional activator. The literature supports both DNA binding to upstream activator sequences and ligand-modulated activation, so GO:0141097 is a better MF endpoint than generic sequence-specific DNA binding.
CUPNH	norR2	IPR002078	GO:0005524	ATP binding	MODIFY	yes	GO:0016887 ATP hydrolysis activity	The InterPro evidence identifies the sigma-54 interaction ATP-binding region, while NorR-family biochemical work shows that NO binding stimulates ATPase activity to activate transcription by RNA polymerase.
CUPNH	norR2	IPR002078	GO:0006355	regulation of DNA-templated transcription	MODIFY	yes	GO:0045893 positive regulation of DNA-templated transcription	The existing term is correct but too broad. Ralstonia studies show NorR is required for transcriptional activation of the norA/norB nitric oxide reductase operon in response to NO.
CUPNH	norR2	IPR002197	GO:0043565	sequence-specific DNA binding	MODIFY	yes	GO:0141097 ligand-modulated transcription activator activity	NorR proteins bind upstream activator sequences and activate sigma-54-dependent transcription in response to NO. GO:0141097 captures this ligand-modulated activator activity more precisely than generic DNA binding.
DANRE	adss1	IPR001114	GO:0000166	nucleotide binding	KEEP_AS_NON_CORE	yes		Nucleotide binding is true but less informative than the adenylosuccinate synthase activity.
DANRE	adss1	IPR001114	GO:0006164	purine nucleotide biosynthetic process	MODIFY	yes	GO:0044208 'de novo' AMP biosynthetic process	Purine nucleotide biosynthesis is correct but broad; ADSS1 specifically supports de novo AMP biosynthesis.
DANRE	adss1	IPR027509	GO:0006167	AMP biosynthetic process	MODIFY	yes	GO:0044208 'de novo' AMP biosynthetic process	AMP biosynthesis is correct but should be narrowed to de novo AMP biosynthesis from IMP.
DANRE	ak2	IPR000850,IPR006259	GO:0005524	ATP binding	KEEP_AS_NON_CORE	yes		ATP binding reflects substrate binding but is less informative than adenylate kinase activity.
DANRE	ak2	IPR006259	GO:0016776	phosphotransferase activity, phosphate group as acceptor	MODIFY	yes	GO:0004017 AMP kinase activity	The broad phosphotransferase annotation should be narrowed to AMP kinase/adenylate kinase activity.
DANRE	ak2	IPR000850	GO:0019205	nucleobase-containing compound kinase activity	MODIFY	yes	GO:0004017 AMP kinase activity	The generic nucleobase-containing compound kinase annotation should be narrowed to AMP kinase/adenylate kinase activity.
DANRE	asah2	IPR006823	GO:0046514	ceramide catabolic process	ACCEPT	no		This annotation matches the synthesized core function or a directly supported core location/process for this gene.
DANRE	cmpk	IPR000850	GO:0005524	ATP binding	KEEP_AS_NON_CORE	yes		The core function is pyrimidine nucleotide kinase activity using ATP as donor.
DANRE	cmpk	IPR006266	GO:0006207	'de novo' pyrimidine nucleobase biosynthetic process	REMOVE	yes		Cmpk phosphorylates existing pyrimidine nucleoside monophosphates; it is not a de novo pyrimidine nucleobase biosynthetic enzyme, and the specific UDP/CDP biosynthetic process annotations are reviewed separately. Falcon deep research positions UMP/CMP kinases in pyrimidine nucleotide interconversion/salvage (converting existing NMPs to NDPs), not in de novo synthesis of the pyrimidine nucleobase ring, reinforcing removal of this term.
DANRE	cmpk	IPR006266	GO:0016776	phosphotransferase activity, phosphate group as acceptor	MODIFY	yes	GO:0033862 UMP kinase activity; GO:0036430 CMP kinase activity; GO:0036431 dCMP kinase activity	The supported functions are the specific UMP/CMP/dCMP kinase activities and CDP/UDP biosynthetic processes.
DANRE	cmpk	IPR000850	GO:0019205	nucleobase-containing compound kinase activity	MODIFY	yes	GO:0033862 UMP kinase activity; GO:0036430 CMP kinase activity; GO:0036431 dCMP kinase activity	The supported functions are the specific UMP/CMP/dCMP kinase activities and CDP/UDP biosynthetic processes.
DANRE	cpt2	IPR000542	GO:0016746	acyltransferase activity	MODIFY	yes	GO:0004095 carnitine O-palmitoyltransferase activity	The broad term is true but under-informative. The specific supported term for cpt2 is carnitine O-palmitoyltransferase activity.
DANRE	crppa	IPR018294	GO:0003824	catalytic activity	MODIFY	yes	GO:0047349 D-ribitol-5-phosphate cytidylyltransferase activity	The generic catalytic activity annotation is true but under-informative for CRPPA.
DANRE	crppa	IPR018294	GO:0008299	isoprenoid biosynthetic process	REMOVE	yes		The vertebrate CRPPA/ISPD role is not MEP/isoprenoid biosynthesis; the relevant vertebrate function is CDP-ribitol production for glycosylation.
DANRE	crppa	IPR034683	GO:0070567	cytidylyltransferase activity	MODIFY	yes	GO:0047349 D-ribitol-5-phosphate cytidylyltransferase activity	The cytidylyltransferase annotation is directionally correct but should be narrowed to D-ribitol-5-phosphate cytidylyltransferase activity.
DANRE	cyp26a1	IPR001128,IPR002401,IPR036396	GO:0004497	monooxygenase activity	KEEP_AS_NON_CORE	yes		This annotation is broad, inferred, or reflects downstream developmental/physiological context rather than the central molecular role.
DANRE	cyp26a1	IPR001128,IPR002401,IPR017972,IPR036396	GO:0005506	iron ion binding	KEEP_AS_NON_CORE	yes		This annotation is broad, inferred, or reflects downstream developmental/physiological context rather than the central molecular role.
DANRE	cyp26a1	IPR001128,IPR002401,IPR017972,IPR036396	GO:0016705	oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen	KEEP_AS_NON_CORE	yes		This annotation is broad, inferred, or reflects downstream developmental/physiological context rather than the central molecular role.
DANRE	cyp26a1	IPR001128,IPR002401,IPR036396	GO:0020037	heme binding	KEEP_AS_NON_CORE	yes		This annotation is broad, inferred, or reflects downstream developmental/physiological context rather than the central molecular role.
DANRE	cyp26b1	IPR001128,IPR002403,IPR036396	GO:0004497	monooxygenase activity	MODIFY	yes	GO:0062183 all-trans retinoic acid 18-hydroxylase activity; GO:0008401 retinoic acid 4-hydroxylase activity	The molecular function should be captured by specific retinoic-acid hydroxylase activities.
DANRE	cyp26b1	IPR001128,IPR002403,IPR017972,IPR036396	GO:0005506	iron ion binding	KEEP_AS_NON_CORE	yes		The core activity is retinoic-acid hydroxylation/catabolism.
DANRE	cyp26b1	IPR001128,IPR002403,IPR017972,IPR036396	GO:0016705	oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen	MODIFY	yes	GO:0062183 all-trans retinoic acid 18-hydroxylase activity; GO:0008401 retinoic acid 4-hydroxylase activity	The molecular function should be captured by specific retinoic-acid hydroxylase activities.
DANRE	cyp26b1	IPR001128,IPR002403,IPR036396	GO:0020037	heme binding	KEEP_AS_NON_CORE	yes		The core activity is retinoic-acid hydroxylation/catabolism.
DANRE	cyp51	IPR001128,IPR002403,IPR036396	GO:0004497	monooxygenase activity	MODIFY	yes	GO:0008398 sterol 14-demethylase activity	Monooxygenase activity is too broad; the supported activity is sterol 14-demethylase.
DANRE	cyp51	IPR001128,IPR002403,IPR017972,IPR036396	GO:0005506	iron ion binding	KEEP_AS_NON_CORE	yes		Iron binding reflects the cytochrome P450 heme center and is less informative than the catalytic activity.
DANRE	cyp51	IPR001128,IPR002403,IPR017972,IPR036396	GO:0016705	oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen	MODIFY	yes	GO:0008398 sterol 14-demethylase activity	The broad oxidoreductase annotation should be replaced with sterol 14-demethylase activity.
DANRE	cyp51	IPR001128,IPR002403,IPR036396	GO:0020037	heme binding	KEEP_AS_NON_CORE	yes		Heme binding is a cofactor/structural feature of cytochrome P450 enzymes, not the core function.
DANRE	dph2	IPR016435	GO:0090560	2-(3-amino-3-carboxypropyl)histidine synthase activity	MARK_AS_OVER_ANNOTATED	yes		The IEA annotation assigns the full enables qualifier, but Dph2 only contributes to the complex activity. The ISS annotation with contributes_to qualifier is the correct representation.
DANRE	fads2	IPR005804	GO:0006629	lipid metabolic process	MODIFY	yes	GO:0006636 unsaturated fatty acid biosynthetic process	The specific supported biological process is unsaturated/polyunsaturated fatty-acid biosynthesis.
DANRE	fads2	IPR012171	GO:0016491	oxidoreductase activity	MODIFY	yes	GO:0016213 acyl-CoA 6-desaturase activity; GO:0062076 acyl-CoA (8-3)-desaturase activity	The molecular function should be represented by the specific acyl-CoA desaturase activities.
DANRE	fen1	IPR008918	GO:0003824	catalytic activity	MODIFY	yes	GO:0017108 5'-flap endonuclease activity	Too generic. The specific nuclease activities already annotated are more appropriate.
DANRE	fen1	IPR006085,IPR006086	GO:0004518	nuclease activity	MODIFY	yes	GO:0017108 5'-flap endonuclease activity	Correct but too generic. More specific nuclease terms are already annotated.
DANRE	fen1	IPR019974,IPR023426	GO:0016788	hydrolase activity, acting on ester bonds	MODIFY	yes	GO:0017108 5'-flap endonuclease activity	Too generic. The specific nuclease activities are more informative and already annotated.
DANRE	flvcr2a	IPR011701,IPR020846	GO:0022857	transmembrane transporter activity	MODIFY	yes	GO:0015220 choline transmembrane transporter activity	The supported molecular function should be the specific choline transmembrane transporter activity; 2024 structural/transport work defines the FLVCR2 family as uniporters rather than coupled/ATP-driven pumps.
DANRE	flvcr2a	IPR011701	GO:0055085	transmembrane transport	MODIFY	yes	GO:0015871 choline transport	The supported biological process should be the specific choline transport process.
DANRE	gmppb	IPR045233	GO:0005525	GTP binding	KEEP_AS_NON_CORE	yes		GTP is a substrate for the guanylyltransferase reaction; the catalytic activity is more informative.
DANRE	gmppb	IPR018357	GO:0016740	transferase activity	MODIFY	yes	GO:0004475 mannose-1-phosphate guanylyltransferase (GTP) activity	The specific supported molecular function is mannose-1-phosphate guanylyltransferase activity.
DANRE	gnptab	IPR002048	GO:0005509	calcium ion binding	KEEP_AS_NON_CORE	yes		This annotation is broad, inferred, or reflects downstream developmental/physiological context rather than the central molecular role.
DANRE	gnptab	IPR021520	GO:0016772	transferase activity, transferring phosphorus-containing groups	KEEP_AS_NON_CORE	yes		This annotation is broad, inferred, or reflects downstream developmental/physiological context rather than the central molecular role.
DANRE	gpat3	IPR002123	GO:0016746	acyltransferase activity	MODIFY	yes	GO:0004366 glycerol-3-phosphate O-acyltransferase activity; GO:0003841 1-acylglycerol-3-phosphate O-acyltransferase activity	The broad term is true but under-informative. The specific supported term for gpat3 is glycerol-3-phosphate O-acyltransferase activity, 1-acylglycerol-3-phosphate O-acyltransferase activity.
DANRE	grk7b	IPR000719,IPR008271	GO:0004672	protein kinase activity	MODIFY	yes	GO:0050254 rhodopsin kinase activity	The broad term is true but under-informative. The specific supported term for grk7b is rhodopsin kinase activity.
DANRE	grk7b	IPR000961	GO:0004674	protein serine/threonine kinase activity	MODIFY	yes	GO:0050254 rhodopsin kinase activity	The broad term is true but under-informative. The specific supported term for grk7b is rhodopsin kinase activity.
DANRE	grk7b	IPR000239	GO:0004703	G protein-coupled receptor kinase activity	MODIFY	yes	GO:0050254 rhodopsin kinase activity	The broad term is true but under-informative. The specific supported term for grk7b is rhodopsin kinase activity.
DANRE	grk7b	IPR000239,IPR000719,IPR000961,IPR017441	GO:0005524	ATP binding	KEEP_AS_NON_CORE	yes		ATP binding is required for kinase catalysis but is less informative than the specific rhodopsin kinase activity.
DANRE	grk7b	IPR000239	GO:0007165	signal transduction	KEEP_AS_NON_CORE	yes		Signal transduction is a broad parent process; the more informative annotation is regulation of photoreceptor signal shutoff.
DANRE	gtpbp3	IPR004520	GO:0003924	GTPase activity	ACCEPT	no		This annotation matches the synthesized core function or a directly supported core location/process for this gene.
DANRE	gtpbp3	IPR004520,IPR005225,IPR006073	GO:0005525	GTP binding	ACCEPT	no		This annotation matches the synthesized core function or a directly supported core location/process for this gene.
DANRE	gtpbp3	IPR004520	GO:0006400	tRNA modification	KEEP_AS_NON_CORE	yes		This annotation is broad, inferred, or reflects downstream developmental/physiological context rather than the central molecular role.
DANRE	he1.2	IPR001506	GO:0004222	metalloendopeptidase activity	ACCEPT	no		This term directly reflects the supported hatching enzyme 1.2 role: FUNCTION: Metalloendopeptidase which participates in the breakdown of the egg envelope during hatching.
DANRE	he1.2	IPR001506,IPR006026	GO:0006508	proteolysis	ACCEPT	no		This term directly reflects the supported hatching enzyme 1.2 role: FUNCTION: Metalloendopeptidase which participates in the breakdown of the egg envelope during hatching.
DANRE	he1.2	IPR006026,IPR024079	GO:0008237	metallopeptidase activity	MODIFY	yes	GO:0004222 metalloendopeptidase activity	The broad term is true but under-informative. The specific supported term for he1.2 is metalloendopeptidase activity.
DANRE	he1.2	IPR006026	GO:0008270	zinc ion binding	KEEP_AS_NON_CORE	yes		Zinc binding is required for catalytic metalloprotease activity, but it is a cofactor/structural annotation rather than the core function.
DANRE	ldhd	IPR004113,IPR016164	GO:0003824	catalytic activity	MODIFY	yes	GO:0140170 D-lactate dehydrogenase (FAD) activity; GO:0140174 (2R)-2-hydroxycarboxylate dehydrogenase activity	The specific supported activities are D-lactate dehydrogenase (FAD) activity and (2R)-2-hydroxycarboxylate dehydrogenase activity.
DANRE	ldhd	IPR004113,IPR006094,IPR016164,IPR036318	GO:0050660	flavin adenine dinucleotide binding	KEEP_AS_NON_CORE	yes		FAD binding is cofactor context; the core molecular function is FAD-dependent D-lactate dehydrogenase activity.
DANRE	ldhd	IPR016166	GO:0071949	FAD binding	KEEP_AS_NON_CORE	yes		FAD binding is captured by the specific FAD-dependent dehydrogenase activity.
DANRE	mfsd2aa	IPR039672	GO:0008643	carbohydrate transport	MARK_AS_OVER_ANNOTATED	yes		The evidence is better explained by the gene core function or downstream phenotype; this term should not be treated as a direct/core annotation.
DANRE	mfsd2aa	IPR039672	GO:0015293	symporter activity	KEEP_AS_NON_CORE	yes		This annotation is broad, inferred, or reflects downstream developmental/physiological context rather than the central molecular role.
DANRE	mfsd2aa	IPR039672	GO:0016020	membrane	REMOVE	yes		The synthesized evidence supports the specific core annotations reviewed separately; this broad or wrong-context annotation should be retired rather than treated as a core function.
DANRE	naa50	IPR000182	GO:0016747	acyltransferase activity, transferring groups other than amino-acyl groups	MODIFY	yes	GO:0120518 protein N-terminal-methionine acetyltransferase activity; GO:0004596 protein-N-terminal amino-acid acetyltransferase activity	The supported activity/process is N-terminal protein acetyltransferase activity and N-terminal protein amino acid acetylation.
DANRE	nags	IPR011243	GO:0006526	L-arginine biosynthetic process	KEEP_AS_NON_CORE	yes		L-arginine biosynthetic process is phylogenetically plausible for some NAGS homologs, but in vertebrates NAGS primarily supports ureagenesis through N-acetylglutamate production; retain as non-core rather than making it the main process.
DANRE	opa1	IPR001401,IPR030381	GO:0005525	GTP binding	ACCEPT	no		This annotation matches the synthesized core function or a directly supported core location/process for this gene.
DANRE	pcif1	IPR039881	GO:0099122	RNA polymerase II C-terminal domain binding	KEEP_AS_NON_CORE	yes		RNA polymerase II CTD binding helps recruit/associate PCIF1 with transcription but is not the core catalytic activity.
DANRE	pex2	IPR025654	GO:0007031	peroxisome organization	ACCEPT	no		This term directly reflects the supported peroxisome biogenesis factor 2 role: FUNCTION: E3 ubiquitin-protein ligase component of a retrotranslocation channel required for peroxisomal protein import.
DANRE	pex2	IPR025654	GO:0008270	zinc ion binding	KEEP_AS_NON_CORE	yes		Zinc ion binding reflects the RING domain cofactor/structural requirement, not the main curation-level function.
DANRE	pex2	IPR025654	GO:0016558	protein import into peroxisome matrix	KEEP_AS_NON_CORE	yes		Retained as a valid contextual or parent annotation, while the core function is represented by ubiquitin protein ligase activity and associated pathway/location terms.
DANRE	pex2	IPR018957	GO:0046872	metal ion binding	KEEP_AS_NON_CORE	yes		Metal ion binding reflects the RING-domain metal coordination needed for structural integrity, not the catalytic ubiquitin-ligase core function. Keep this as non-core, consistent with the more specific zinc ion binding annotation.
DANRE	polb	IPR002008,IPR002054,IPR003583,IPR018944,IPR022312	GO:0003677	DNA binding	KEEP_AS_NON_CORE	yes		The core function is base-excision repair polymerase/5-dRP lyase activity.
DANRE	polb	IPR002008,IPR003583,IPR022312	GO:0006281	DNA repair	REMOVE	yes		The specific biological process supported for Polb is base-excision repair, which is already separately ACCEPTed; broad DNA metabolism/repair/biosynthesis annotations should be retired rather than modified to molecular-function terms.
DANRE	polb	IPR019843	GO:0016779	nucleotidyltransferase activity	MODIFY	yes	GO:0003887 DNA-directed DNA polymerase activity; GO:0051575 5'-deoxyribose-5-phosphate lyase activity	The supported process/function should be narrowed to base-excision repair and DNA-directed DNA polymerase/5-dRP lyase activity.
DANRE	pomt2	IPR003342	GO:0000030	mannosyltransferase activity	MODIFY	yes	GO:0004169 dolichyl-phosphate-mannose-protein mannosyltransferase activity	The broad term is true but under-informative. The specific supported term for pomt2 is dolichyl-phosphate-mannose-protein mannosyltransferase activity.
DANRE	pomt2	IPR003342	GO:0006493	protein O-linked glycosylation	MODIFY	yes	GO:0035269 protein O-linked glycosylation via mannose	The broad term is true but under-informative. The specific supported term for pomt2 is protein O-linked glycosylation via mannose.
DANRE	pomt2	IPR003342	GO:0016020	membrane	ACCEPT	no		This term directly reflects the supported protein O-mannosyltransferase 2 role: FUNCTION: Transfers mannosyl residues to the hydroxyl group of serine or threonine residues.
DANRE	prmt6	IPR025799	GO:0016274	protein-arginine N-methyltransferase activity	ACCEPT	no		This is the core molecular function of Prmt6, a SAM-dependent type I protein arginine methyltransferase. Falcon confirms PRMT6 transfers methyl groups from SAM to arginine residues to form MMA and then ADMA.
DANRE	rpe65a	IPR004294	GO:0016702	oxidoreductase activity, acting on single donors with incorporation of molecular oxygen, incorporation of two atoms of oxygen	MODIFY	yes	GO:0052885 all-trans-retinyl-ester hydrolase, 11-cis retinol forming activity; GO:0050251 retinol isomerase activity	This term implies dioxygen incorporation, but Rpe65a does not activate molecular oxygen: its iron acts as a Lewis acid for coupled ester hydrolysis and trans-cis isomerization. The annotation should be replaced by the specific isomerohydrolase/retinol isomerase functions. Falcon explicitly contrasts RPE65 with oxygenase carotenoid cleavage dioxygenases.
DANRE	slc15a2	IPR018456	GO:0006857	oligopeptide transport	MARK_AS_OVER_ANNOTATED	yes		PEPT2 does transport oligopeptides (di-/tripeptides), so the term is biologically accurate, but it is non-specific given that the precise di-/tripeptide import processes (GO:0140206, GO:0140207) and peptide:proton symporter activity (GO:0015333) are already separately ACCEPTed. Flagged as over-annotated rather than removed to preserve its biological validity.
DANRE	slc15a2	IPR000109,IPR018456	GO:0016020	membrane	MARK_AS_OVER_ANNOTATED	yes		PEPT2 is a membrane protein, so the term is not wrong, but it is a root-level over-annotation subsumed by the specific plasma membrane (GO:0005886) and apical plasma membrane (GO:0016324) locations already ACCEPTed.
DANRE	slc15a2	IPR000109,IPR018456	GO:0022857	transmembrane transporter activity	MODIFY	yes	GO:0015333 peptide:proton symporter activity; GO:0071916 dipeptide transmembrane transporter activity	The supported annotation should specify peptide:proton symport and di-/tripeptide import across the plasma membrane.
DANRE	slc15a2	IPR000109	GO:0055085	transmembrane transport	MARK_AS_OVER_ANNOTATED	yes		PEPT2 does perform transmembrane transport, so the term is biologically accurate, but it is non-specific given that the precise di-/tripeptide import processes (GO:0140206, GO:0140207) are already separately ACCEPTed. Flagged as over-annotated rather than removed to preserve its biological validity.
DANRE	slc25a37	IPR002067	GO:0055085	transmembrane transport	MODIFY	yes	GO:0048250 iron import into the mitochondrion	The direct supported process is iron import into the mitochondrion.
DANRE	slc39a14	IPR003689	GO:0016020	membrane	KEEP_AS_NON_CORE	yes		This annotation is broad, inferred, or reflects downstream developmental/physiological context rather than the central molecular role.
DANRE	slc39a14	IPR003689	GO:0030001	metal ion transport	ACCEPT	no		This annotation matches the synthesized core function or a directly supported core location/process for this gene.
DANRE	slc39a14	IPR003689	GO:0046873	metal ion transmembrane transporter activity	KEEP_AS_NON_CORE	yes		This annotation is broad, inferred, or reflects downstream developmental/physiological context rather than the central molecular role.
DANRE	slc39a14	IPR003689	GO:0055085	transmembrane transport	KEEP_AS_NON_CORE	yes		This annotation is broad, inferred, or reflects downstream developmental/physiological context rather than the central molecular role.
DANRE	slc5a12	IPR001734	GO:0016020	membrane	MODIFY	yes	GO:0016324 apical plasma membrane	The supported location is apical plasma membrane.
DANRE	slc5a12	IPR001734	GO:0055085	transmembrane transport	MODIFY	yes	GO:0015718 monocarboxylic acid transport; GO:1905039 carboxylic acid transmembrane transport	The direct process is monocarboxylic acid transport/carboxylic acid transmembrane transport.
DANRE	spns1	IPR011701,IPR020846	GO:0022857	transmembrane transporter activity	ACCEPT	no		Transmembrane transporter activity is the best available general MF annotation for the lysosomal transporter role; a substrate-specific term is proposed in proposed_new_terms.
DANRE	spns1	IPR011701	GO:0055085	transmembrane transport	MODIFY	yes	GO:0051977 lysophospholipid transport	Transmembrane transport is correct but overly general; the substrate-specific process term lysophospholipid transport (GO:0051977) is a better, same-aspect (BP) description of spns1's direct biological process.
DANRE	sult1st2	IPR000863	GO:0008146	sulfotransferase activity	MODIFY	yes	GO:0004062 aryl sulfotransferase activity; GO:0004304 estrone sulfotransferase activity	The review should use the more informative aryl and estrone sulfotransferase activities supported by substrate testing.
DANRE	tdp2	IPR005135	GO:0003824	catalytic activity	MODIFY	yes	GO:0070260 5'-tyrosyl-DNA phosphodiesterase activity; GO:0070259 tyrosyl-DNA phosphodiesterase activity	The supported molecular function is tyrosyl-DNA phosphodiesterase activity.
DANRE	tomt	IPR002935	GO:0008171	O-methyltransferase activity	KEEP_AS_NON_CORE	yes		The predicted SAM-dependent methyltransferase domain is present and required for rescue, so this molecular function is plausible by-similarity context. Falcon shows the physiological MET role does not depend on canonical methyltransferase catalysis and no endogenous methyl-acceptor substrate is identified, so this term is non-core.
DANRE	tpp1	IPR036852	GO:0004252	serine-type endopeptidase activity	KEEP_AS_NON_CORE	yes		Tpp1 is primarily an exopeptidase with only limited endopeptidase activity; this endopeptidase-specific IEA term (from the broad Peptidase_S8/S53 fold) overstates the specificity and is retained as non-core, consistent with the GO:0004175 endopeptidase activity parent.
DANRE	tpp1	IPR000209,IPR030400,IPR036852	GO:0006508	proteolysis	ACCEPT	no		Tpp1 is a lysosomal serine tripeptidyl-peptidase acting in proteolysis.
DANRE	tpp1	IPR000209,IPR015366	GO:0008236	serine-type peptidase activity	MODIFY	yes	GO:0008240 tripeptidyl-peptidase activity	The specific molecular function is tripeptidyl-peptidase activity.
DANRE	trpm7	IPR005821	GO:0005216	monoatomic ion channel activity	ACCEPT	no		TRPM7 functions as an ion channel that conducts monoatomic cations. This is a core molecular function, though more specific terms also apply.
DANRE	trpm7	IPR032415,IPR037162	GO:0051262	protein tetramerization	ACCEPT	no		TRPM7 forms tetrameric channel complexes via its coiled-coil domain. This is essential for channel assembly and function.
DANRE	trpm7	IPR005821	GO:0055085	transmembrane transport	ACCEPT	no		TRPM7 mediates transmembrane transport of ions. Core function though more specific terms also apply.
DANRE	ucp2	IPR002067	GO:0055085	transmembrane transport	MODIFY	yes	GO:1990542 mitochondrial transmembrane transport	The generic transmembrane transport annotation is true but should be narrowed to mitochondrial transmembrane transport.
DANRE	urad	IPR017580	GO:0000255	allantoin metabolic process	ACCEPT	no		This term directly reflects urad's role in producing allantoin. The enzyme generates (S)-allantoin as the product of the final uricolysis step, so participation in allantoin metabolic process is well supported.
DAPPU	DpuGr29	IPR013604	GO:0016020	membrane	ACCEPT	no		The annotation is accurate - DpuGr29 contains the 7TM chemoreceptor domain (IPR013604) which is a multi-pass transmembrane domain. While GO:0016020 (membrane) is a more general term than GO:0005886 (plasma membrane), both annotations are appropriate. The IEA annotation based on InterPro domain mapping is well-supported by structural predictions showing 7-8 transmembrane helices.
DAPPU	DpuGr29	IPR013604	GO:0050909	sensory perception of taste	MODIFY	yes	GO:0007606 sensory perception of chemical stimulus	The term GO:0050909 (sensory perception of taste) implies terrestrial-style gustation, but Daphnia lives in aquatic environments where chemicals are detected in solution. The distinction between taste and smell in aquatic organisms is blurred. A more appropriate annotation would be GO:0007606 (sensory perception of chemical stimulus), which is the parent term that encompasses both taste and smell without implying a specific modality. Given no direct evidence for DpuGr29 ligands or expression site, we cannot determine if this gene functions in contact chemosensation vs. distant chemosensation.
DEIRA	Q9RSY6	IPR003029	GO:0003676	nucleic acid binding	MARK_AS_OVER_ANNOTATED	yes		GO:0003729 (mRNA binding) already annotates this protein at a more informative level. The generic parent term nucleic acid binding is redundant and represents an over-annotation from automatic InterPro2GO mapping.
DESPS	nrfA	IPR017570	GO:0005509	calcium ion binding	KEEP_AS_NON_CORE	yes		InterPro detects cytochrome c-552/nitrite reductase family features, and NrfA enzymes are multiheme cytochromes. Calcium binding may be associated with the fold, but the direct functional annotation should center on heme binding and ammonia-forming nitrite reductase activity.
DESRO	K9IFY6	IPR000827,IPR001811,IPR036048	GO:0006955	immune response	PENDING	no		TODO: Review this GOA annotation
DESRO	K9IFY6	IPR000827,IPR001811,IPR036048,IPR039809	GO:0008009	chemokine activity	PENDING	no		TODO: Review this GOA annotation
DESRO	K9IIP0	IPR000538	GO:0005540	hyaluronic acid binding	UNDECIDED	yes		Potential binding activity is uncertain for this DESRO protein due to UniProt caution.
DESRO	K9IUF6	IPR013274	GO:0008270	zinc ion binding	UNDECIDED	yes		Binding predictions are uncertain given the caution about conserved residues.
DESRO	K9IWR0	IPR002960,IPR006052,IPR006053	GO:0006955	immune response	MARK_AS_OVER_ANNOTATED	yes		General immune response annotation is inferred and not directly supported.
DESRO	K9IWX5	IPR018244	GO:0005576	extracellular region	UNDECIDED	yes		No direct evidence for extracellular localization of this CRISP-like protein in DESRO; UniProt cautions against feature propagation.
DESRO	K9J287	IPR005135	GO:0003824	catalytic activity	MODIFY	yes	GO:0004530 deoxyribonuclease I activity	Use the specific deoxyribonuclease I activity term.
DESRO	K9J287	IPR016202	GO:0004536	DNA nuclease activity	MODIFY	yes	GO:0004530 deoxyribonuclease I activity	Use the specific deoxyribonuclease I activity term.
DESRO	K9J2R0	IPR002471	GO:0004252	serine-type endopeptidase activity	MODIFY	yes	GO:0008239 dipeptidyl-peptidase activity	DPP4 is a dipeptidyl peptidase (EC 3.4.14.5).
DESVH	P07598	IPR013352	GO:0005506	iron ion binding	ACCEPT	no		The annotation is technically correct as confirmed by structural studies (PMID:10368269). HydA binds iron both in [4Fe-4S] clusters and in the binuclear H-cluster active site. However, this is a parent term of more specific annotations already present.
DESVH	Q725T7	IPR001757	GO:0016887	ATP hydrolysis activity	ACCEPT	no		ATP hydrolysis is the energy-providing reaction that drives K+ transport in KdpFABC. KdpB is the catalytic subunit responsible for this hydrolysis. The reaction (ATP + H2O = ADP + phosphate) is coupled to conformational changes that translocate K+. This is a core molecular function that should be retained alongside GO:0008556.
DESVH	Q725T8	IPR003820	GO:0016020	membrane	KEEP_AS_NON_CORE	yes		KdpC is indeed a membrane protein, so this annotation is not incorrect. However, GO:0005886 (plasma membrane) is more specific and accurately describes KdpC's localization. This broader term adds no additional information. It derives from InterPro domain IPR003820 which appropriately associates KdpC with membranes.
DESVH	Q725T9	IPR003852	GO:0004673	protein histidine kinase activity	REMOVE	yes		DVU_3336 lacks the HisKA domain containing the conserved phosphorylatable histidine residue and lacks the HATPase_c domain required for ATP hydrolysis and phosphotransfer. The protein is 379 aa with domains at positions 13-218 (KdpD N-terminal sensor) and 243-357 (UspA). There is no sequence region corresponding to histidine kinase catalytic function. This is a clear case of over-annotation where a sensory domain associated with kinases was incorrectly annotated as having kinase activity.
DESVH	Q725T9	IPR003852	GO:0016020	membrane	ACCEPT	no		"Membrane localization is consistent with KdpD-like sensors. While more specific than ""plasma membrane"" would be ideal, this general term is acceptable as a broader annotation alongside the more specific plasma membrane annotation. Both annotations capture the membrane association of this sensory protein."
DESVH	Q725U0	IPR013767	GO:0006355	regulation of DNA-templated transcription	REMOVE	yes		This annotation represents an over-annotation based on the PAS domain. The PAS domain in DVU_3335 functions as a signal sensor, not as a DNA-binding or transcriptional regulatory domain. The protein lacks any DNA-binding domains and is a membrane-associated sensor with two transmembrane helices. While the phosphorelay cascade may ultimately affect transcription via the response regulator, the sensor kinase itself does not directly regulate transcription. This annotation conflates the downstream effect of phosphorelay signaling with the direct function of the sensor kinase.
DESVH	Q725U0	IPR003661,IPR036097	GO:0007165	signal transduction	ACCEPT	no		While redundant with the more specific GO:0000160, this general annotation is not incorrect. It was inferred from the HisK_dim/P domains (IPR003661, IPR036097) which are hallmarks of signal transducing histidine kinases. Retaining both allows for different levels of annotation granularity in queries. The IEA annotation is valid and consistent with domain-based inference.
DESVH	Q725U0	IPR004358	GO:0016772	transferase activity, transferring phosphorus-containing groups	ACCEPT	no		This annotation bridges the GO hierarchy between general transferase activity and specific kinase activity. It was correctly inferred from the histidine kinase-like C-terminal domain (IPR004358). While less informative than GO:0000155 or GO:0004673, it is a valid IEA annotation that accurately describes the biochemical class of reaction catalyzed. The annotation is acceptable as part of the annotation hierarchy.
DESVH	Q726C4	IPR012845	GO:0003899	DNA-directed RNA polymerase activity	REMOVE	yes		"FliA is a sigma factor, not an RNA polymerase enzyme. Sigma factors function by binding to the RNA polymerase core to form a holoenzyme and directing it to specific promoters; they do not possess catalytic polymerase activity. This annotation appears to be an over-annotation based on InterPro domain associations (GO_REF:0000002). The UniProt record correctly identifies Q726C4 as ""RNA polymerase sigma factor"" not as RNA polymerase itself. This distinction is critical for accurate functional annotation."
DESVH	Q726C4	IPR000943,IPR007627,IPR007630,IPR012845,IPR013325,IPR014284	GO:0006352	DNA-templated transcription initiation	ACCEPT	no		This biological process annotation is accurate. Sigma factors function specifically in transcription initiation - they bind RNAP core to form the holoenzyme, recognize and bind promoter sequences, facilitate open complex formation, and are released after initiation. FliA participates in transcription initiation of late flagellar genes including flagellin, hook-associated proteins, motor components, and chemotaxis genes.
DESVH	Q729Q8	IPR001501	GO:0016151	nickel cation binding	PENDING	no		TODO: Review this GOA annotation
DESVH	Q729Q8	IPR001135	GO:0016651	oxidoreductase activity, acting on NAD(P)H	PENDING	no		TODO: Review this GOA annotation
DESVH	Q729Q8	IPR001135	GO:0048038	quinone binding	PENDING	no		TODO: Review this GOA annotation
DESVH	Q729Q8	IPR001135	GO:0051287	NAD binding	PENDING	no		TODO: Review this GOA annotation
DESVH	Q72AS0	IPR018194	GO:0008901	ferredoxin hydrogenase activity	MODIFY	yes	GO:0047806 cytochrome-c3 hydrogenase activity	"The annotation is based on domain similarity but assigns an incorrect electron partner (ferredoxin) and incorrect reaction direction (H2 production vs uptake). D. vulgaris Hildenborough periplasmic [NiFe] hydrogenases function as H2 uptake enzymes with cytochrome c3 as the immediate acceptor. ""Periplasmic electron transfer proceeds primarily to tetraheme cytochrome c3 (TpIc3; DVU3171)"" as summarized in the deep research report. The more appropriate term is GO:0047806 (cytochrome-c3 hydrogenase activity) which describes the correct reaction with the physiological acceptor."
DESVH	Q72AS0	IPR001501,IPR018194	GO:0016151	nickel cation binding	ACCEPT	no		"[NiFe] hydrogenases are defined by their bimetallic active site containing nickel and iron. ""The [NiFe] active sites contain a heterobimetallic Ni-Fe center with diatomic ligands (CO and CN-) on Fe"" (deep research). UniProt structural annotation confirms multiple Ni(2+) binding residues in this protein. This is a core functional property of all [NiFe] hydrogenases."
DESVH	Q72AS3	IPR018194	GO:0008901	ferredoxin hydrogenase activity	PENDING	no		TODO: Review this GOA annotation
DESVH	Q72AS3	IPR001501,IPR018194	GO:0016151	nickel cation binding	PENDING	no		TODO: Review this GOA annotation
DESVH	Q72B50	IPR000943,IPR007624,IPR007627,IPR007630,IPR009042,IPR013325,IPR014284	GO:0003700	DNA-binding transcription factor activity	MODIFY	yes	GO:0016987 sigma factor activity	Sigma factors have a distinct molecular function (GO:0016987 sigma factor activity) that is fundamentally different from transcription factor activity. Sigma factors do not bind DNA independently - they only bind promoter DNA when part of the RNAP holoenzyme. The GO guidelines explicitly note that sigma factors should be annotated to sigma factor activity, not transcription factor activity. This InterPro-derived annotation is an over-generalization.
DESVH	Q72BK7	IPR000394,IPR007634	GO:0001216	DNA-binding transcription activator activity	REMOVE	yes		The deep research clearly establishes that sigma-54 forms a transcriptionally inactive closed complex with RNAP and requires ATP-dependent remodeling by EBPs to form the open complex. This is fundamentally different from transcription activators which directly enhance transcription. Sigma-54 actually INHIBITS transcription until EBPs activate it. The IEA annotation from InterPro domains IPR000394 and IPR007634 conflates promoter recognition with transcription activation, which are mechanistically distinct for sigma-54. GO:0016987 (sigma factor activity) correctly captures this function.
DESVH	Q72BK7	IPR007046	GO:0006352	DNA-templated transcription initiation	ACCEPT	no		This biological process annotation is appropriate. Sigma-54 is essential for transcription initiation at its cognate promoters. The requirement for EBP activation does not negate its role in initiation - it defines the specific mechanism. In D. vulgaris, 87 sigma-54-dependent promoters drive transcription initiation of 85 operons.
DESVH	Q72BM9	IPR003148,IPR006037,IPR036721	GO:0006813	potassium ion transport	ACCEPT	no		GO:0006813 (potassium ion transport) describes the directed movement of K+ ions by means of transporters or pores, which includes regulatory subunits that are essential for this process. TrkA/KtrA proteins are obligate components of the functional Trk/Ktr K+ uptake system, and without them the pore cannot be properly gated. The annotation is acceptable as it captures the biological process in which the protein participates, even though its specific role is regulatory rather than catalytic.
DESVH	Q72BM9	IPR006037	GO:0008324	monoatomic cation transmembrane transporter activity	MODIFY	yes	GO:0015459 potassium channel regulator activity; GO:0005524 ATP binding	Transporter activity terms should be reserved for proteins that directly enable the movement of substrates across membranes. TrkA/KtrA RCK proteins regulate transporter activity by binding to and modulating the TrkH/KtrB membrane pore. The 2024 structural study demonstrates that KtrA binds ATP/ADP at RCK interfaces and undergoes square-to-diamond conformational transitions that mechanically gate the associated pore. This is regulator activity, not transporter activity. The most appropriate term is GO:0015459 (potassium channel regulator activity) which specifically describes proteins that bind to and modulate K+ channels/transporters.
DESVH	Q72BQ0	IPR000943,IPR007627,IPR007630,IPR009042,IPR013325,IPR014284	GO:0006352	DNA-templated transcription initiation	ACCEPT	no		This biological process annotation is accurate for sigma factors. RpoH directly participates in DNA-templated transcription initiation by forming the holoenzyme with core RNA polymerase and enabling promoter recognition. The sigma subunit is released after promoter escape/clearance but is essential for the initiation phase. This is consistent with the InterPro-based evidence source.
DESVH	Q72F05	IPR003445	GO:0006812	monoatomic cation transport	MODIFY	yes	GO:0006813 potassium ion transport	The Cat_transpt domain (IPR003445) is found in cation transporters, but TrkH-family proteins have evolved specificity for K+. Structural and biochemical evidence from homologous systems confirms K+ selectivity, warranting a more specific term.
DESVH	Q72F05	IPR003445	GO:0008324	monoatomic cation transmembrane transporter activity	MODIFY	yes	GO:0015079 potassium ion transmembrane transporter activity	TrkH-family proteins function specifically as K+ channels. The protein enables transfer of K+ ions across the membrane through a selectivity filter, with activity regulated by the RCK domain of the cognate TrkA partner. A more specific MF term better captures the actual molecular function.
DESVH	Q72F05	IPR003445	GO:0055085	transmembrane transport	KEEP_AS_NON_CORE	yes		This very general term is implied by more specific annotations. It is not incorrect, but adds no functional insight beyond what is captured by potassium-specific terms. Keeping as non-core maintains the hierarchical relationship without cluttering the core annotation set.
DESVH	Q72F06	IPR003148,IPR006037,IPR036721	GO:0006813	potassium ion transport	MODIFY	yes	GO:0043266 regulation of potassium ion transport	"The RCK domains in Q72F06 form a cytosolic gating ring - they do not span the membrane or create an ion conduction pathway. The membrane-spanning TrkH/KtrB partner (not Q72F06) is the actual transporter. As stated in the deep research: ""DVU_0412 itself is not the pore but the ligand-gated regulator controlling K+ flux through the membrane partner."""
DESVH	Q72F06	IPR006037	GO:0008324	monoatomic cation transmembrane transporter activity	MODIFY	yes	GO:0015459 potassium channel regulator activity	Q72F06 has RCK domains (5-121 aa RCK_N, 138-221 aa RCK_C per UniProt) but no transmembrane segments. It cannot itself transport ions across membranes. Instead, it binds ATP/ADP and undergoes conformational changes that gate the associated TrkH/KtrB membrane channel. This is a classic channel regulator function.
DESVH	Q72FD5	IPR001902	GO:0055085	transmembrane transport	ACCEPT	no		The annotation is correct. DVU_0279 is a member of the SulP/SLC26 family of anion transporters, which are well-characterized secondary-active transporters. While more specific process terms exist (such as GO:1902358 sulfate transmembrane transport), the evidence suggests DVU_0279 may not be primarily a sulfate transporter. The comparative genomics analysis places DVU_0279 with DauA-like dicarboxylate transporters, and it is not essential for sulfate uptake in D. vulgaris. Therefore, the general term GO:0055085 is appropriately conservative until experimental data clarify substrate specificity.
DICDI	mlcD	IPR002048	GO:0005509	calcium ion binding	KEEP_AS_NON_CORE	yes		The InterPro2GO inference from EF-hand domains is technically correct (MlcD does bind calcium) but functionally misleading. Three of four EF-hands have degenerate calcium-coordinating residues, and the measured Kd of 52 uM is far above physiological calcium concentrations. This is not a core function.
DICDI	nip7	IPR002478,IPR036974	GO:0003723	RNA binding	ACCEPT	no		RNA binding via the PUA domain is experimentally verified for Nip7 orthologs. While rRNA binding (GO:0019843) would be more specific, RNA binding is not incorrect and the IEA evidence appropriately reflects the domain-level annotation.
DICDI	nip7	IPR016686	GO:0005634	nucleus	KEEP_AS_NON_CORE	yes		Correct but less specific than the nucleolus annotation. The nucleolus is within the nucleus, so this is technically true but the more informative annotation is GO:0005730 nucleolus.
DICDI	nip7	IPR016686	GO:0042255	ribosome assembly	KEEP_AS_NON_CORE	yes		Correct parent term but less specific than GO:0042273 (ribosomal large subunit biogenesis) which is already present with IBA and ISS evidence. The InterPro2GO mapping appropriately captures the family-level biology.
DOROP	ADAR2	IPR002466	GO:0004000	adenosine deaminase activity	MODIFY	yes	GO:0003726 double-stranded RNA adenosine deaminase activity	GO:0004000 (adenosine deaminase activity) describes the deamination of free adenosine, which is the activity of ADA enzymes, not ADAR enzymes. ADAR2 specifically deaminates adenosine residues within double-stranded RNA. The correct term GO:0003726 is already annotated, so this annotation should be replaced to avoid confusion between ADA and ADAR activities.
DORPE	AP180	IPR011417	GO:0005543	phospholipid binding	ACCEPT	no		"Phospholipid binding is a valid parent term for the ANTH domain activity. While GO:0005546 (PtdIns(4,5)P2 binding) is more specific and also annotated, this broader InterPro-derived annotation is not incorrect and captures general lipid binding capacity of the ANTH domain. The UniProt record notes the protein ""Binds clathrin and phosphatidylinositol 4,5-bisphosphate."""
DORPE	AP180	IPR014712	GO:0030276	clathrin binding	ACCEPT	no		Clathrin binding is a central and well-demonstrated function of squid AP180. The protein directly binds clathrin triskelia via DLL motifs in its C-terminal domain and promotes their assembly into clathrin lattices (PMID:10575017, PMID:11102472).
DORPE	AP180	IPR014712,IPR045192	GO:0048268	clathrin coat assembly	ACCEPT	no		Clathrin coat assembly is the defining function of AP180. This IEA annotation is fully supported by IDA evidence from PMID:10575017 and PMID:12807910 for the same gene.
DORPE	P21613	IPR001752,IPR019821,IPR027640	GO:0003777	microtubule motor activity	MODIFY	yes	GO:0008574 plus-end-directed microtubule motor activity	Kinesin-1 is specifically a plus-end-directed motor. The term microtubule motor activity is correct but less precise than plus-end-directed microtubule motor activity. Single-molecule assays confirm processive plus-end-directed movement of squid kinesin along microtubules (Rangan and Reck-Peterson 2023).
DORPE	P21613	IPR001752,IPR019821	GO:0005524	ATP binding	ACCEPT	no		ATP binding is fundamental to kinesin function. The UniProt entry identifies the ATP binding site at residues 85-92, and the protein belongs to the TRAFAC class myosin-kinesin ATPase superfamily. The kinesin motor domain hydrolyzes ATP to produce force.
DORPE	P21613	IPR001752,IPR019821,IPR027640	GO:0007018	microtubule-based movement	ACCEPT	no		Microtubule-based movement is the core process enabled by kinesin-1. This is well established from decades of squid axoplasm transport studies. While anterograde axonal transport is the more precise process, this broader term is also appropriate.
DORPE	P21613	IPR001752	GO:0008017	microtubule binding	ACCEPT	no		Microtubule binding is fundamental to kinesin motor function. The UniProt entry identifies a specific microtubule-binding region (residues 173-314). Single-molecule studies of squid kinesin directly demonstrate microtubule binding and processive movement along microtubules (Rangan and Reck-Peterson 2023).
DORPE	TDO	IPR037217	GO:0046872	metal ion binding	MARK_AS_OVER_ANNOTATED	yes		While technically correct (TDO binds iron via heme), GO:0046872 (metal ion binding) is too generic to be informative. The heme binding annotation (GO:0020037) already captures this function at a more appropriate level of specificity. The metal ion binding term does not add useful functional information beyond what heme binding conveys.
DORPE	cpx	IPR008849	GO:0006836	neurotransmitter transport	MODIFY	yes	GO:2000302 positive regulation of synaptic vesicle exocytosis	Neurotransmitter transport implies a direct role in moving neurotransmitter molecules, which is misleading. Complexin regulates exocytosis of neurotransmitter-containing synaptic vesicles at a late prefusion step. The correct process is regulation of neurotransmitter secretion or synaptic vesicle exocytosis, not transport per se.
DROME	Akt1	IPR000719,IPR008271	GO:0004672	protein kinase activity	KEEP_AS_NON_CORE	yes		Catalytic activity confirms protein kinase function.
DROME	Buffy	IPR026298,IPR036834	GO:0042981	regulation of apoptotic process	MODIFY	yes	GO:0043066 negative regulation of apoptotic process	"While technically correct, experimental evidence strongly supports Buffy's primary role as an ANTI-apoptotic regulator (negative regulation). ""Buffy, the second Drosophila Bcl-2-like protein, is a pro-survival protein"" (PMID:12853472). The term GO:0043066 (negative regulation of apoptotic process) is more specific and better reflects the core function. The generic ""regulation"" term obscures Buffy's actual role."
DROME	Ccs	IPR024134	GO:0005507	copper ion binding	ACCEPT	no		"Accept. As a copper chaperone, Ccs must bind copper to transfer it to SOD1. Drosophila Ccs uniquely lacks the N-terminal MXCXXC copper-binding motif but retains the C-terminal CXC domain III motif that is essential for copper transfer [PMID:18948262 ""domain III contains a critical CXC copper-binding site that inserts copper""]. Falcon deep research confirms this Drosophila-specific loss of the canonical domain I motif while retaining copper-delivery function."
DROME	Ccs	IPR001424,IPR036423	GO:0006801	superoxide metabolic process	MARK_AS_OVER_ANNOTATED	yes		"Over-annotation. Ccs does not directly metabolize superoxide. It functions upstream as a copper chaperone that activates SOD1. SOD1 is the enzyme that directly metabolizes superoxide. The term ""superoxide metabolic process"" belongs on SOD1, not Ccs [PMID:18948262]. Falcon deep research confirms the primary role is SOD1 maturation, not direct superoxide metabolism."
DROME	Edem2	IPR001382,IPR036026,IPR037322,IPR044674	GO:0004571	mannosyl-oligosaccharide 1,2-alpha-mannosidase activity	ACCEPT	no		Consistent with IBA annotation and GH47 family membership. The InterPro mapping is appropriate for this domain-based molecular function.
DROME	Edem2	IPR001382,IPR036026	GO:0005509	calcium ion binding	ACCEPT	no		Calcium binding is documented in the UniProt record as a cofactor for the GH47 mannosidase domain. The InterPro mapping is appropriate.
DROME	Edem2	IPR012341	GO:0005975	carbohydrate metabolic process	MARK_AS_OVER_ANNOTATED	yes		Too broad to be informative. EDEM2 is involved in ER mannose trimming and ERAD, not general carbohydrate metabolism. The more specific terms GO:1904380, GO:0097466, and GO:0036503 are already annotated and are much more informative.
DROME	Edem2	IPR001382,IPR036026	GO:0016020	membrane	ACCEPT	no		Acceptable as a broad localization term. EDEM2 is associated with the ER membrane system. The more specific ER annotation is more informative.
DROME	Edem2	IPR044674	GO:1904380	endoplasmic reticulum mannose trimming	ACCEPT	no		ER mannose trimming is a core biological process for EDEM2, directly related to its role in ERAD substrate recognition via mannose trimming of N-glycans. The InterPro mapping is appropriate. Falcon deep research supports EDEM2 acting as an alpha-1,2-mannose trimming enzyme on high-mannose N-glycans of misfolded glycoproteins, with conserved framing placing EDEM2 at the first mannose-trimming step initiating gpERAD.
DROME	Hsp83	IPR001404,IPR019805	GO:0006457	protein folding	ACCEPT	no		Correct. Redundant with IBA annotation. InterPro correctly maps the HSP90 domain to the protein folding process.
DROME	Hsp83	IPR001404	GO:0016887	ATP hydrolysis activity	ACCEPT	no		Correct. Redundant with IBA annotation. InterPro correctly maps the HSP90 HATPase domain to ATP hydrolysis activity.
DROME	Hsp83	IPR001404,IPR019805	GO:0051082	unfolded protein binding	MODIFY	yes	GO:0140662 ATP-dependent protein folding chaperone	"Same issue as the IBA annotation for this term. GO:0051082 is proposed for obsoletion and does not accurately represent the HSP90 mechanism. Should be replaced with GO:0140662 ""ATP-dependent protein folding chaperone."""
DROME	Hsp83	IPR001404	GO:0140662	ATP-dependent protein folding chaperone	ACCEPT	no		This is the most accurate MF term for HSP90 function. HSP90 binds client proteins and assists their folding/maturation through ATP hydrolysis-driven conformational changes.
DROME	Iml1	IPR027244	GO:0005096	GTPase activator activity	KEEP_AS_NON_CORE	yes		GTPase-activating activity is established for GATOR1 (RagA/B), so the IEA/ISS is reasonable for Iml1 but not the primary focus.
DROME	Lkb1	IPR039154	GO:0001558	regulation of cell growth	KEEP_AS_NON_CORE	yes		LKB1 negatively regulates organ growth via apoptosis.
DROME	Lkb1	IPR000719,IPR008271	GO:0004672	protein kinase activity	KEEP_AS_NON_CORE	yes		Catalytic activity confirms protein kinase function.
DROME	Lkb1	IPR039154	GO:0030010	establishment of cell polarity	KEEP_AS_NON_CORE	yes		Lkb1 is required for oocyte A-P polarity and epithelial polarity.
DROME	Lkb1	IPR039154	GO:0030295	protein kinase activator activity	KEEP_AS_NON_CORE	yes		LKB1 regulates AMPK and other AMPK-related kinases.
DROME	Lkb1	IPR039154	GO:0042593	glucose homeostasis	UNDECIDED	yes		Available sources focus on lipid metabolism and polarity rather than glucose homeostasis.
DROME	Nmnat	IPR004821	GO:0003824	catalytic activity	ACCEPT	no		Broad but not wrong. This InterPro-based IEA annotation is consistent with the known enzymatic function. More specific child terms are annotated at IDA level.
DROME	Nprl3	IPR005365	GO:0032007	negative regulation of TOR signaling	MODIFY	yes	GO:1904262 negative regulation of TORC1 signaling	Evidence supports inhibition of TORC1 specifically; replace with the TORC1-specific term.
DROME	Pdk1	IPR000719,IPR008271	GO:0004672	protein kinase activity	KEEP_AS_NON_CORE	yes		Protein kinase activity is supported by its serine/threonine kinase function.
DROME	gcl	IPR043380	GO:0007281	germ cell development	KEEP_AS_NON_CORE	yes		Accept but as non-core. GCL is required for germ cell specification (pole cell formation), which is the very first step of germ cell development. However, the more specific terms pole cell formation (GO:0007279) and pole cell fate determination (GO:0007278) are more informative for GCL's actual role. The IEA annotation via InterPro (IPR043380, Germ cell-less protein-like) is correct in assigning this broad term. Note there is also an IGI annotation below with direct experimental evidence.
DROME	Git	IPR047161	GO:0007420	brain development	ACCEPT	no		The IEA annotation correctly captures Git's role in brain development, which is directly demonstrated in Drosophila by IMP evidence (PMID:25792865) showing reduced brain size and mushroom body defects in dGit mutants.
DROME	Git	IPR047161	GO:0032012	regulation of ARF protein signal transduction	ACCEPT	no		The IEA annotation is correct and consistent with the IBA annotation and experimental data showing Git's function in regulating ARF signaling, particularly Arf79F in the context of Hippo pathway activation.
DROME	jar	IPR001609,IPR004009,IPR008989	GO:0003774	cytoskeletal motor activity	ACCEPT	no		Correct mapping. jar is a bona fide actin-activated ATPase motor, directly demonstrated to catalyze particle transport (PMID:8202156).
DROME	jar	IPR001609,IPR004009,IPR008989	GO:0005524	ATP binding	ACCEPT	no		Correct. The motor domain contains the P-loop NTPase fold with ATP-binding motifs (PMID:1429838). ATP hydrolysis powers the motor activity.
DROME	jar	IPR001609,IPR004009	GO:0016459	myosin complex	MODIFY	yes	GO:0016461 unconventional myosin complex	While not wrong, the more specific term GO:0016461 (unconventional myosin complex) is already annotated with IDA evidence (PMID:9472041). The IEA annotation to the parent term is redundant and less informative.
DROME	jar	IPR008989	GO:0051015	actin filament binding	ACCEPT	no		Correct, well supported by direct experimental evidence (PMID:16571671 IDA).
DROME	rdgBbeta	IPR001666	GO:0015914	phospholipid transport	ACCEPT	no		Phospholipid transport is the direct biological process consequence of PI transfer activity. The PITP domain mediates monomeric lipid transfer between membranes. This is well-supported by the domain architecture and ortholog biochemistry. Falcon deep research frames the RdgBβ subfamily as coupling PI metabolism with PA handling, most plausibly acting locally at membranes after recruitment rather than as a bulk cytosolic transfer activity.
DROME	sws	IPR001423	GO:0046470	phosphatidylcholine metabolic process	ACCEPT	no		Automated annotation consistent with experimental evidence. The IDA evidence (PMID:15772346) confirms this biological process.
DROVI	B4MAQ2	IPR001494	GO:0006886	intracellular protein transport	MODIFY	yes	GO:0006405 RNA export from nucleus	The annotation confounds the transport of the receptor itself (which shuttles as a protein) with the cargo it carries. Exportin-5 transports RNA cargo, not protein cargo. A more accurate process term would reflect RNA transport.
DROVI	B4MAQ2	IPR001494	GO:0031267	small GTPase binding	ACCEPT	no		"Small GTPase (Ran) binding is a mechanistically essential function of all karyopherin-beta transport receptors, including Exportin-5. The annotation is correct, though a more specific term like ""Ran GTPase binding"" (GO:0005099) would be more informative if available in the annotation pipelines."
ECO57	nleB1	IPR057545	GO:0106362	protein-arginine N-acetylglucosaminyltransferase activity	ACCEPT	no		Correct and appropriate annotation. This GO term precisely describes NleB1's enzymatic activity. UniProt lists this exact term with IDA evidence from PMID:28522607 and PMID:30619781. The IEA annotation from InterPro is consistent with experimental evidence.
ECOLI	DnaJ	IPR012724	GO:0005524	ATP binding	REMOVE	yes		DnaJ does not bind ATP. It stimulates the ATPase activity of DnaK (the Hsp70), which is the ATP-binding partner. UniProt does not list ATP binding as a feature of DnaJ, and no experimental evidence supports direct ATP binding by DnaJ. This is an erroneous IEA mapping from the DnaJ family InterPro entry.
ECOLI	DnaJ	IPR008971,IPR012724	GO:0006457	protein folding	ACCEPT	no		Protein folding is a core biological process for DnaJ. Consistent with IDA evidence from PMID:9103205 and PMID:7559385.
ECOLI	DnaJ	IPR012724	GO:0009408	response to heat	ACCEPT	no		Well-supported. DnaJ is a classic heat shock protein (HSP40). Consistent with IMP from PMID:2144273 and IEP from PMID:8349564.
ECOLI	DnaJ	IPR001305	GO:0031072	heat shock protein binding	ACCEPT	no		While GO:0051087 is more specific and already annotated, this broader IEA annotation is not incorrect. DnaJ binds DnaK (Hsp70), which is a heat shock protein. The IEA mapping from InterPro is reasonable.
ECOLI	DnaK	IPR012725	GO:0006457	protein folding	ACCEPT	no		Protein folding is the core biological process in which DnaK participates. This IEA is consistent with the extensive experimental evidence.
ECOLI	DnaK	IPR013126	GO:0016887	ATP hydrolysis activity	ACCEPT	no		Correct. Duplicate of the IBA annotation but from a different evidence source. ATP hydrolysis is central to DnaK function.
ECOLI	DnaK	IPR012725	GO:0051082	unfolded protein binding	MODIFY	yes	GO:0044183 protein folding chaperone	GO:0051082 is proposed for obsoletion. DnaK's binding of unfolded proteins is mechanistically part of its ATP-dependent foldase cycle, not passive binding. The correct MF is GO:0044183 or its child GO:0140662. DnaK can also function as a holdase in some contexts (PMID:2203539, ATP-independent protection from aggregation), but the holdase NTR has not yet been created.
ECOLI	GroEL	IPR018370	GO:0006457	protein folding	ACCEPT	no		Correct electronic inference. The GroEL/Hsp60 InterPro domain is directly associated with protein folding function. Consistent with all other evidence.
ECOLI	GroEL	IPR001844	GO:0140662	ATP-dependent protein folding chaperone	ACCEPT	no		"This is the correct and most specific molecular function term for GroEL. It captures both the ATP dependence and the protein folding chaperone activity. UniProt catalytic activity: ""ATP + H2O + an unfolded polypeptide = ADP + phosphate + a folded polypeptide"" (EC 5.6.1.7, PMID:9285585, PMID:9285593). This IEA annotation should ideally be supported by experimental evidence as well."
ECOLI	HdeA	IPR024972,IPR036831	GO:0030288	outer membrane-bounded periplasmic space	ACCEPT	no		Correct localization. HdeA is a secreted periplasmic protein. Multiple studies confirm periplasmic localization including direct protein sequencing from periplasmic fractions (PMID:9298646) and UniProt annotation with signal peptide (residues 1-21). The IEA is redundant with the IDA but not incorrect.
ECOLI	HdeA	IPR024972,IPR036831	GO:0071468	cellular response to acidic pH	ACCEPT	no		Correct and well-supported. HdeA is activated by acidic pH and functions specifically in the acid stress response. GO:0071468 is broader than GO:1990451 which is annotated with IMP evidence from PMID:10623550. The broader IEA is not wrong.
ECOLI	HdeB	IPR028623	GO:0009268	response to pH	ACCEPT	no		While this is a broader IEA term, it is not incorrect. HdeB is fundamentally a pH-responsive chaperone. The more specific term GO:0010447 is already annotated with IDA/IMP evidence, so this broader IEA is acceptable as a supporting annotation.
ECOLI	HdeB	IPR028623	GO:0051082	unfolded protein binding	MODIFY	yes	GO:0140309 unfolded protein carrier activity	"HdeB functions as an ATP-independent holdase chaperone that prevents aggregation of periplasmic proteins at acidic pH (PMID:17085547). The term GO:0051082 ""unfolded protein binding"" describes only the binding aspect, not the chaperone activity. GO:0140309 ""unfolded protein carrier activity"" (a protein carrier activity that binds a protein in an unfolded state, prevents its aggregation, and escorts it to an acceptor or location) better captures the ATP-independent holdase chaperone function and is well supported by the falcon deep research, which independently characterizes HdeB as an ""acid-activated, ATP-independent holdase chaperone"" that binds unfolding periplasmic proteins and prevents their irreversible aggregation."
ECOLI	SecB	IPR003708	GO:0051082	unfolded protein binding	MODIFY	yes	GO:0140309 unfolded protein carrier activity	Same rationale as the IBA annotation for GO:0051082. SecB does not merely bind unfolded proteins; it actively carries them to SecA. GO:0140309 (unfolded protein carrier activity) is the appropriate replacement.
ECOLI	SecB	IPR003708	GO:0051262	protein tetramerization	ACCEPT	no		"SecB is a well-characterized homotetramer. Watanabe and Blobel determined SecB is ""a 64-kDa tetramer consisting of four identical 16-kDa subunits"" (PMID:2649892). The crystal structure confirms the dimer-of-dimers architecture (UniProt cites PubMed:14643199, PubMed:27501151). While tetramerization is structural rather than a core evolved function, the annotation is factually accurate."
ECOLI	Skp	IPR005632	GO:0051082	unfolded protein binding	MODIFY	yes	GO:0140309 unfolded protein carrier activity	GO:0051082 is being reviewed for obsoletion. Skp functions as an unfolded protein carrier -- it binds unfolded OMPs at the inner membrane and escorts them across the periplasm to the BAM complex for outer membrane insertion. This is a carrier/escort function, not merely binding.
ECOLI	arnF	IPR000390	GO:0016020	membrane	ACCEPT	no		This is a correct but very broad cellular component annotation. ArnF is unquestionably a membrane protein (4 TM helices, integral inner membrane protein). While GO:0005886 (plasma membrane) is more informative and is already annotated via IBA, IDA, and IEA, keeping this broader IEA annotation is acceptable as it provides the InterPro-derived evidence.
ECOLI	arnF	IPR022832	GO:1901505	carbohydrate derivative transmembrane transporter activity	ACCEPT	no		This annotation is accurate -- the substrate translocated by the ArnE/ArnF flippase is undecaprenyl phosphate-alpha-L-Ara4N, which is a carbohydrate derivative (containing L-Ara4N, a modified arabinose). This is more informative than the generic 'transmembrane transporter activity' and is consistent with the IMP annotation to the same term from PMID:17928292.
ECOLI	bcp	IPR000866	GO:0016209	antioxidant activity	KEEP_AS_NON_CORE	yes		Correct but too general. The specific peroxidase activity terms (GO:0008379, GO:0140824) are more informative for describing BCP function. Retained as a broad parent annotation from InterPro2GO.
ECOLI	bcp	IPR000866	GO:0016491	oxidoreductase activity	MARK_AS_OVER_ANNOTATED	yes		Uninformatively broad grandparent term, fully subsumed by the specific molecular function annotations (GO:0008379, GO:0140824) that capture the experimentally characterized thioredoxin-dependent peroxidase reaction. This IEA term adds no curation value beyond the specific peroxidase terms.
ECOLI	fepE	IPR003856	GO:0016020	membrane	ACCEPT	no		FepE is a multi-pass membrane protein. The term is broader than the more specific plasma membrane annotations but is not wrong. IEA annotations mapping to broader terms are acceptable even when more specific annotations exist.
ECOLI	ftsI	IPR037532	GO:0008955	peptidoglycan glycosyltransferase activity	REMOVE	yes		"This is a well-documented error. Meeske et al. 2016 [PMID:27525505] clearly state that Class B PBPs ""have TP domains but lack PGT activity."" The glycosyltransferase activity is provided by SEDS proteins (FtsW for division, RodA for elongation), not by Class B PBPs like FtsI. The InterPro mapping that generated this IEA annotation is incorrect for FtsI."
ECOLI	manX	IPR013789	GO:0008643	carbohydrate transport	ACCEPT	no		Correct but general. ManX participates in the transport of multiple sugars including mannose, glucose, fructose, and N-acetylglucosamine. More specific transport annotations exist (GO:0015761, GO:0098708, GO:1990539, GO:0015764) but this broader IEA term is not wrong.
ECOLI	manX	IPR004720,IPR018455,IPR036667	GO:0008982	protein-N(PI)-phosphohistidine-sugar phosphotransferase activity	ACCEPT	no		Correct IEA annotation consistent with the IBA and experimentally supported function. ManX contains PTS EIIA and EIIB domains that mediate phosphotransfer (PMID:2681202, PMID:8262947).
ECOLI	manX	IPR004701,IPR004720,IPR018455,IPR036662,IPR036667	GO:0009401	phosphoenolpyruvate-dependent sugar phosphotransferase system	ACCEPT	no		Correct IEA annotation. ManX is a core component of the PEP-dependent sugar PTS (PMID:2951378, PMID:2999119). Duplicates more authoritative evidence codes for the same term.
ECOLI	manX	IPR004701,IPR036662	GO:0016020	membrane	ACCEPT	no		Not incorrect but very general. ManX associates with the inner membrane as a peripheral membrane protein (PMID:2999119). More specific terms (GO:0005886) are also present. Acceptable as a broad IEA annotation.
ECOLI	manX	IPR013789	GO:0016773	phosphotransferase activity, alcohol group as acceptor	ACCEPT	no		Correct but very general IEA annotation. ManX phosphorylates sugar substrates at hydroxyl groups. More specific MF terms are already annotated. Acceptable as a broad IEA mapping.
ECOLI	manY	IPR004700	GO:0016020	membrane	ACCEPT	no		While this is a less specific term than GO:0005886, it is technically correct and IEA annotations at a broader level than experimentally supported ones are acceptable. The InterPro mapping from PTS_IIC_man domain is appropriate.
ECOLI	manY	IPR004700	GO:0009401	phosphoenolpyruvate-dependent sugar phosphotransferase system	ACCEPT	no		Correct IEA annotation that is consistent with and redundant to the experimentally supported and phylogenetically inferred annotations.
ECOLI	manZ	IPR004704	GO:0009401	phosphoenolpyruvate-dependent sugar phosphotransferase system	ACCEPT	no		This IEA annotation from InterPro domain mapping is redundant with experimental annotations but is not incorrect. The InterPro domain PTS_IID_man correctly maps to PTS involvement.
ECOLI	manZ	IPR004704	GO:0016020	membrane	ACCEPT	no		While this is less specific than the plasma membrane annotation, it is not incorrect. IEA annotations at broader levels are acceptable when more specific experimental annotations also exist.
ECOLI	mrdA	IPR017790	GO:0016020	membrane	MARK_AS_OVER_ANNOTATED	yes		This is a parent term of GO:0005886 (plasma membrane). Since multiple experimental and computational annotations already exist for the more specific term plasma membrane, this generic membrane annotation is redundant and less informative.
ECOLI	rbsD	IPR007721,IPR023750	GO:0048029	monosaccharide binding	ACCEPT	no		As an enzyme that acts on D-ribose, RbsD necessarily binds monosaccharides. The UniProt entry documents substrate binding residues at positions 28, 106, and 128-130. This annotation is consistent with the catalytic function and supported by structural data.
ECOLI	rbsD	IPR007721,IPR023750	GO:0005996	monosaccharide metabolic process	ACCEPT	no		While very general, this is not incorrect - D-ribose catabolism is a type of monosaccharide metabolic process. The more specific GO:0019303 annotations provide the informative biological context, but this hierarchical parent annotation is acceptable for InterPro-based IEA.
ECOLI	rlmC	IPR011825	GO:0016070	RNA metabolic process	KEEP_AS_NON_CORE	yes		Extremely broad parent term. Redundant with more specific biological process annotations (rRNA base methylation, rRNA methylation). Provides no additional functional insight.
ECOLI	rlmC	IPR011825	GO:0016436	rRNA (uridine) methyltransferase activity	MODIFY	yes	GO:0070041 rRNA (uridine-C5-)-methyltransferase activity	The evidence supports the more specific term GO:0070041 (rRNA (uridine-C5-)- methyltransferase activity), which specifies the C5 position. Consistent with the action for the IMP-evidenced annotation of the same term.
ECOLI	surA	IPR023034	GO:0030288	outer membrane-bounded periplasmic space	ACCEPT	no		The InterPro-derived localization is correct and supported by multiple experimental studies. Redundant with IDA and IBA annotations but acceptable.
ECOLI	surA	IPR023034	GO:0042277	peptide binding	ACCEPT	no		SurA does bind peptide motifs as part of its substrate recognition mechanism. While more specific terms might be preferable, this general IEA annotation is not incorrect. SurA's N-terminal domain and C-terminal tail form the peptide binding site for OMP recognition.
ECOLI	surA	IPR023034	GO:0043165	Gram-negative-bacterium-type cell outer membrane assembly	ACCEPT	no		Consistent with experimental evidence. SurA depletion causes marked decrease in outer membrane density (PMID:17908933), confirming its essential role in outer membrane assembly.
ECOLI	surA	IPR023034	GO:0050821	protein stabilization	ACCEPT	no		Consistent with experimental evidence showing SurA prevents OMP degradation and misfolding. Redundant with IMP annotations but acceptable as an IEA.
ECOLI	yciO	IPR006070	GO:0003725	double-stranded RNA binding	UNDECIDED	yes		The InterPro-based prediction of dsRNA binding is plausible given the large positively charged surface unique to YciO proteins (PMID:40703034), but there is no direct experimental evidence for dsRNA binding specifically. The genomic context (colocalization with rnm genes encoding RNase AM, a rRNA maturation enzyme) suggests rRNA interaction may be more likely. Without experimental evidence, it is difficult to determine whether dsRNA binding or a more specific RNA binding term is appropriate. The annotation should be revisited when experimental data on YciO RNA binding become available.
ECOLI	yegV	IPR002139,IPR002173	GO:0016301	kinase activity	MODIFY	yes	GO:0019200 carbohydrate kinase activity	"While kinase activity (GO:0016301) is not wrong, a more informative term is available. YegV is specifically annotated by UniProt as an ""uncharacterized sugar kinase"" belonging to the PfkB carbohydrate kinase family (Pfam PF00294). CDD classifies it in the YegV_kinase_like subfamily (cd01944). The term GO:0019200 (carbohydrate kinase activity), defined as ""catalysis of the transfer of a phosphate group to a carbohydrate"", would be more specific and appropriate. This term correctly captures the sugar kinase function predicted from domain architecture without specifying an incorrect substrate. De Crecy-Lagard et al. 2025 (PMID:40703034) specifically noted that while the first three digits of the EC number (2.7.1) are reliably predicted for YegV, the specific substrate (4th digit) is unknown, making GO:0019200 the right level of specificity."
ECOLI	yjhQ	IPR000182	GO:0016747	acyltransferase activity, transferring groups other than amino-acyl groups	ACCEPT	no		Straightforward domain-based annotation. The GNAT domain (IPR000182) maps to acyltransferase activity, which is appropriate for the structural fold. Redundant with the IBA annotation but independently derived and valid.
ECOLX	ereB	IPR007815	GO:0046677	response to antibiotic	ACCEPT	no		EreB directly confers erythromycin resistance by enzymatic antibiotic inactivation. The key missing annotation is the molecular function.
ECOLX	mcr-1	IPR012549	GO:0016020	membrane	MODIFY	yes	GO:0005886 plasma membrane	Generic location term; the specific bacterial inner-membrane location (GO:0005886) is preferred.
ECOLX	mcr-1	IPR040423	GO:0016772	transferase activity, transferring phosphorus-containing groups	MODIFY	yes	GO:0043838 phosphatidylethanolamine:Kdo2-lipid A phosphoethanolamine transferase activity	The specific, experimentally and structurally supported molecular function should replace this over-general parent term.
ECOLX	mcr2	IPR012549	GO:0016020	membrane	MODIFY	yes	GO:0005886 plasma membrane	Use plasma membrane rather than the generic membrane term where possible.
ECOLX	mcr2	IPR040423	GO:0016772	transferase activity, transferring phosphorus-containing groups	MODIFY	yes	GO:0043838 phosphatidylethanolamine:Kdo2-lipid A phosphoethanolamine transferase activity	Replace the broad or over-specific electronic term 'transferase activity, transferring phosphorus-containing groups' with phosphatidylethanolamine:Kdo2-lipid A phosphoethanolamine transferase activity based on UniProt/CARD determinant identity and the curated ARO->GO mapping.
ENTCL	aac6-Ib	IPR000182	GO:0016747	acyltransferase activity, transferring groups other than amino-acyl groups	MODIFY	yes	GO:0047663 aminoglycoside 6'-N-acetyltransferase activity	Over-general parent; replace with GO:0047663.
FERPA	Ferp_0128	IPR002429	GO:0004129	cytochrome-c oxidase activity	REMOVE	yes	GO:0050304 nitrous-oxide reductase activity	The InterPro cytochrome c oxidase subunit II-like domain reflects the copper-binding domain architecture shared with NosZ-like enzymes, but the protein-level assignment is nitrous-oxide reductase EC 1.7.2.4. The specific GO:0050304 annotation is present and should be used instead. Family research confirms that PTHR42838 mixes NosZ and cytochrome c oxidase subunit II-like CuA proteins, making this exact over-annotation risk predictable.
FERPA	Ferp_0128	IPR002429	GO:0005507	copper ion binding	ACCEPT	no		NosZ enzymes are copper proteins, and the UniProt record annotates both copper binding and NosZ/cytochrome oxidase subunit II copper-binding domains for this sequence. Falcon supports a NosZ-family copper enzyme, but does not provide Ferp_0128-specific metal stoichiometry.
FUSNU	pepV	IPR010964	GO:0008270	zinc ion binding	ACCEPT	no		Structural studies of PepV (Lactobacillus delbrueckii, PDB 1LFW) and the homologous PepD (Vibrio alginolyticus) establish a dinuclear zinc active site whose metals stabilize the tetrahedral intermediate and activate the catalytic water. The UniProt cofactor annotation (Zn2+) and InterPro IPR010964 support zinc binding. Note that some characterized PepV homologs (S. hominis ShPepV, S. aureus SaPepV) are functionally Mn2+-preferential in vitro, so the active site is more generally a divalent-metal centre; a broader GO:0046872 (metal ion binding) is also defensible, but di-zinc is the best-documented structural assignment and is retained.
FUSNU	pepV	IPR010964	GO:0016805	dipeptidase activity	ACCEPT	no		PepV proteins are biochemically established broad-specificity dipeptidases. ShPepV cleaved all L-amino-acid dipeptides tested (except D-Ala-D-Ala) but could not cleave a tripeptide, and L. delbrueckii PepV is a nonspecific amino dipeptidase. The InterPro IPR010964 signature and UniProt dipeptidase keyword directly assign this function to A0A133P372. This is the best-supported molecular function and is a core function of the gene. Direct assay of the F. nucleatum protein has not been done, so the IEA evidence is appropriate, but the assignment is strongly supported by family signatures and homolog biochemistry.
FUSNU	pepV		GO:0008237	metallopeptidase activity	NEW	no		The M20A PepV enzymes are metallopeptidases that depend on active-site divalent metals to activate the catalytic water; ShPepV/SaPepV are metal-dependent and Mn2+-preferential in vitro, and PepV crystal structures contain a dinuclear metal centre. The UniProt Metalloprotease keyword and the GOA metallopeptidase mapping support this. It is retained as a core molecular function alongside dipeptidase activity.
FUSNU	pepV		GO:0070573	metallodipeptidase activity	NEW	no		The protein's dipeptidase activity (GO:0016805) and metallopeptidase activity (GO:0008237) are both supported; the more specific term GO:0070573 (metallodipeptidase activity) unifies these and is the single most informative MF term for a metal-dependent PepV dipeptidase. Supported by homolog biochemistry showing metal-dependent dipeptide hydrolysis.
FUSNU	pepV		GO:0043171	peptide catabolic process	NEW	no		Beyond the generic proteolysis term, the biological role of a dipeptidase is the catabolic breakdown of peptides to liberate amino acids. F. nucleatum preferentially utilizes proteins and peptides and possesses intracellular dipeptidase activities; dipeptides such as glutamylglutamate support its growth. GO:0043171 (peptide catabolic process) captures this role. Evidence is organism-level plus homolog inference (no direct assay of this protein), so the IEA-level evidence is appropriate.
FUSNU	pepV		GO:0005737	cytoplasm	NEW	no		Subcellular fractionation of S. aureus showed PepV is primarily cytosolic with only a minute membrane fraction, and it lacks an N-terminal signal sequence. F. nucleatum dipeptidase activity is described as intracellular. The F. nucleatum protein likewise has no signal peptide annotated. Cytoplasmic localization is therefore the most defensible compartment, supported by homolog evidence; marked at IEA level since this protein was not directly localized.
HYPJE	cbh1	IPR001722,IPR037019	GO:0004553	hydrolase activity, hydrolyzing O-glycosyl compounds	MODIFY	yes	GO:0016162 cellulose 1,4-beta-cellobiosidase activity	This is a broad parent term that is correct but non-specific. The more specific term GO:0016162 (cellulose 1,4-beta-cellobiosidase activity) better describes CBHI's molecular function.
HYPJE	cbh1	IPR000254,IPR001722,IPR035971,IPR037019	GO:0005975	carbohydrate metabolic process	MODIFY	yes	GO:0030245 cellulose catabolic process	This is a very broad biological process term. While correct, the more specific term GO:0030245 (cellulose catabolic process) better captures CBHI's primary biological role.
HYPJE	cbh1	IPR000254,IPR035971	GO:0030248	cellulose binding	ACCEPT	no		Correct annotation. CBHI contains a well-characterized cellulose-binding module (CBM family 1) that specifically binds to insoluble cellulose fibers via aromatic residues and hydrogen bonds.
JUGRE	A0A2I4G8T1	IPR002213	GO:0008194	UDP-glycosyltransferase activity	KEEP_AS_NON_CORE	yes		This is a true parent term of GO:0035251. The protein does have UDP-glycosyltransferase activity, but the more specific UDP-glucosyltransferase activity better captures its function. Keeping as non-core since it is correct but less informative.
LENH9	haox	IPR012133	GO:0010181	FMN binding	ACCEPT	no		Correct annotation. UniProt record confirms FMN cofactor requirement and binding sites are annotated (residues 92-94, 121, 143, 171, 240, 262, 295-299, 319). Deep mechanistic analysis confirms FMN undergoes oxidation/reduction cycles during catalysis, with electrons transferred from L-lactate substrate to FMN cofactor, followed by reaction with O2 to regenerate oxidized flavin. This annotation is essential and well-supported.
MAIZE	AM1	IPR044221	GO:0007131	reciprocal meiotic recombination	ACCEPT	no		"Supported by both the InterPro family signature and direct experimental evidence. The UniProt FUNCTION statement explicitly states AM1 is ""Required for homologous chromosome pairing, and initiation and progression of meiotic recombination"" [PMID:19204280]. In am1 mutants the recombination program fails to install: wild-type meiocytes show ~500 RAD51 foci per nucleus at mid-zygotene, whereas no RAD51 foci are detected in am1-1 or am1-praI. The IBA/IEA term is at an appropriate level of specificity for AM1's role in enabling reciprocal (crossover) recombination."
MAIZE	AM1	IPR044221	GO:0051177	meiotic sister chromatid cohesion	KEEP_AS_NON_CORE	yes		The annotation is biologically reasonable but reflects an upstream, permissive role rather than AM1 being a cohesion component itself. AM1 is required for chromatin localization of AFD1 (the maize REC8/Rec8 meiotic cohesin) and ASY1, which are absent or strongly reduced in am1-1 [PMID:19204280]; thus loss of AM1 indirectly disrupts meiotic sister chromatid cohesion. AM1 is not a cohesin or cohesin-loading enzyme - it is a chromatin-associated regulator that licenses the broader meiotic chromosome program of which cohesion is one part. The term is correct as a downstream-of-AM1 consequence but is best classified as non-core; the core biology is the meiotic-entry / chromosome- structure / recombination program.
MAIZE	AM1	IPR044221	GO:0051321	meiotic cell cycle	ACCEPT	no		Core, well-supported function and the most appropriate broad process term for AM1. In strong am1 alleles, cells that should become meiocytes instead execute mitosis-like (equational) divisions rather than meiosis, demonstrating that AM1 is required to commit cells to and progress through the meiotic cell cycle [PMID:19204280]. The InterPro family signature for the DYAD/AMEIOTIC1 group correctly assigns this term. It duplicates the IMP annotation to the same term; both are accepted as core.
MAIZE	CHIB	IPR016283	GO:0005975	carbohydrate metabolic process	MARK_AS_OVER_ANNOTATED	yes		"Not wrong - chitin is a carbohydrate (polysaccharide) and its hydrolysis is carbohydrate metabolism - but ""carbohydrate metabolic process"" is a high-level grouping term that conveys little once the specific process ""chitin catabolic process"" (GO:0006032, also present in the current GOA) is annotated. The precise function is endo-hydrolysis of chitin. Retaining the vague parent adds no information beyond the specific term, so it is best treated as an over-annotation."
MAIZE	CHIB	IPR000726	GO:0006032	chitin catabolic process	ACCEPT	no		"Correct and at the right level of specificity. CHIB hydrolyzes the beta-1,4 linkages of chitin, a beta-(1->4)-linked N-acetyl-D-glucosamine polysaccharide, breaking it down into chitooligosaccharides - precisely ""chitin catabolic process"". This is the core biological process and is more informative than the generic parents ""carbohydrate metabolic process"" and ""polysaccharide catabolic process""."
MAIZE	CHIB	IPR001002,IPR018371,IPR036861	GO:0008061	chitin binding	ACCEPT	no		Correct and supported by the protein architecture. CHIB has an N-terminal hevein-type chitin-binding domain (Chitin-binding type-1, residues 34-68); the CAZy CBM18 / Pfam Chitin_bind_1 assignments confirm the module. The chitin-binding domain enhances activity on insoluble chitin and contributes to antifungal effectiveness. This molecular function is a genuine, specific accessory activity supporting substrate engagement.
MAIZE	CHIB	IPR000726	GO:0016998	cell wall macromolecule catabolic process	KEEP_AS_NON_CORE	yes		"Reasonable and biologically meaningful: chitin is a structural component of fungal cell walls, and a secreted plant endochitinase degrades fungal-cell-wall chitin as the basis of its antifungal action. The term is correct but is a process-level framing of the same activity already captured by ""chitin catabolic process"" (GO:0006032), which is the core, more direct term. Retain this as a non-core descriptor of the host-defense context (degradation of the microbial cell-wall macromolecule) rather than as the primary process."
MAIZE	EZ1	IPR045318	GO:0006338	chromatin remodeling	MODIFY	yes	GO:0031507 heterochromatin formation	"The essence (EZ1 alters chromatin state) is correct, but ""chromatin remodeling"" (GO:0006338) conventionally denotes dynamic, often ATP-dependent reorganization of nucleosome structure, whereas EZ1/MEZ1 acts by depositing a covalent histone mark (H3K27 methylation) to establish a repressive chromatin state. The biology is more precisely captured by ""heterochromatin formation"" (GO:0031507), which is the established process for E(z)/PRC2-mediated H3K27me3 silencing and is already present via the IBA annotation. Modify to the more specific and accurate process term."
MAIZE	EZ1	IPR045318	GO:0042054	histone methyltransferase activity	MODIFY	yes	GO:0046976 histone H3K27 methyltransferase activity	"The annotation is correct but too general. EZ1/MEZ1 is an E(z)-class enzyme that specifically methylates Lys-27 of histone H3; the deep research concludes it is a SAM-dependent histone lysine methyltransferase acting on H3K27, consistent with its EC assignment in UniProt (EC 2.1.1.356) and its E(z)-class SET domain conservation. The generic ""histone methyltransferase activity"" should be modified to the substrate-specific ""histone H3K27 methyltransferase activity"" (GO:0046976), which is already annotated (IBA/IEA) and captures the true catalytic specificity."
MAIZE	O6	IPR001574,IPR016138,IPR017988,IPR036041	GO:0017148	negative regulation of translation	ACCEPT	no		Correct and core to RIP biology. RIPs inactivate ribosomes as rRNA N-glycosidases, depurinating the conserved sarcin-ricin-loop adenine and thereby blocking the elongation-factor-dependent steps of translation; maize b-32 inhibits protein synthesis in vitro (IC50 ~28-66 pM for the activated alpha-beta form) consistent with this mechanism. The process term is the direct biological consequence of the catalytic molecular function (GO:0030598) and is appropriate at this level of specificity.
MAIZE	VP1	IPR003340	GO:0003677	DNA binding	ACCEPT	no		"Correct and core. The UniProt feature table annotates a TF-B3 DNA-binding domain at 517-619, and the deep-research synthesis confirms that VP1/ABI3 proteins contain four conserved domains in which B3 is the DNA-binding domain, with direct B3-dependent binding to the C1 promoter Sph element. ""DNA binding"" is generic but not incorrect; the more informative sequence-specific DNA-binding transcription factor activity is captured by GO:0003700 (modified below). Note that the founding study (McCarty et al. 1991) localized VP1's transactivation activity to an acidic domain and proposed that VP1 ""may bind to DNA indirectly"" for several targets (UniProt FUNCTION), so generic DNA binding rather than direct sequence-specific binding is the safe MF claim for the bulk of VP1 targets; direct B3-mediated binding is documented specifically for C1/Sph."
MAIZE	VP1	IPR044800	GO:0003700	DNA-binding transcription factor activity	MODIFY	yes	GO:0000981 DNA-binding transcription factor activity, RNA polymerase II-specific	"VP1 is unambiguously a sequence-specific DNA-binding transcription factor: it acts as a direct transcriptional activator of certain promoters via B3 DNA binding (C1 via the Sph element), as an ABA-dependent co-activator of seed maturation genes via G-box/ABRE elements, and as a repressor of germination genes. UniProt's original description (Cell 1991) is ""a novel transcriptional activator."" Because VP1 regulates RNA polymerase II protein-coding genes, the generic GO:0003700 is better represented by the more specific child term GO:0000981 (DNA-binding transcription factor activity, RNA polymerase II-specific). The essence is correct; only the level of specificity is refined."
MEDTR	NFP	IPR000719,IPR001245,IPR008266	GO:0004672	protein kinase activity	REMOVE	yes		"Although less obviously wrong than the retired tyrosine-kinase keyword, ""protein kinase activity"" has the same underlying problem: it asserts a catalytic molecular function that NFP does not have. NFP is an experimentally established pseudokinase (""NFP did not show autophosphorylation activity ... deviations from conserved kinase sequences""; PMID:16844829), and signalling requires the active co-receptor kinase LYK3 (PMID:25351493). The kinase domain functions as a protein-interaction/scaffolding module (e.g. it binds the GTPase ROP10; PMID:25794934), not as an enzyme. An IEA term that contradicts direct experimental evidence should not be retained. REMOVE; the genuine molecular function (signalling receptor / Nod factor perception) is captured by the proposed NEW annotations below."
MEDTR	NFP	IPR000719	GO:0005524	ATP binding	KEEP_AS_NON_CORE	yes		The P-loop/VAIK motif elements predicted by sequence (UniProt BINDING 290-298 and 339) make residual ATP binding plausible even though NFP is catalytically inactive, and ATP binding by a pseudokinase does not imply catalysis. The annotation is not contradicted by experiment, but it is not a core function: NFP's defining role is ligand perception, not nucleotide chemistry, and no study has demonstrated functional ATP binding. Retain as a plausible domain-derived prediction, marked non-core.
METBS	A0A0B4FWC3	IPR034686	GO:0010333	terpene synthase activity	MODIFY	yes	GO:0010334 sesquiterpene synthase activity	Correct but should be more specific - this is a sesquiterpene synthase with EC 4.2.3.163 and 4.2.3.171.
METBS	MBR_10393	IPR034686	GO:0010333	terpene synthase activity	MODIFY	yes	GO:0010334 sesquiterpene synthase activity	The enzyme is specifically a sesquiterpene synthase with well-characterized products (corvol ethers A and B) and assigned EC numbers. The more specific term GO:0010334 accurately reflects its molecular function.
METBS	Mlac1	IPR002355,IPR011706,IPR011707	GO:0005507	copper ion binding	ACCEPT	no		Correct. The enzyme binds 4 copper ions per monomer, which are essential for its laccase activity.
METBS	Pks1	IPR018201	GO:0004315	3-oxoacyl-[acyl-carrier-protein] synthase activity	MODIFY	yes	GO:0016218 polyketide synthase activity	Partially correct but too specific to just the KS domain activity. The full protein has polyketide synthase activity which encompasses this plus other activities.
METBS	Pks1	IPR016039	GO:0016746	acyltransferase activity	MODIFY	yes	GO:0016218 polyketide synthase activity	Correct for MAT and SAT domains but too general for the overall protein function. Should use polyketide synthase activity.
METBS	Pks1	IPR020806	GO:0031177	phosphopantetheine binding	ACCEPT	no		Correct for the ACP domains which bind phosphopantetheine cofactors. This is an important functional aspect.
METEA	ackA	IPR004372	GO:0006082	organic acid metabolic process	KEEP_AS_NON_CORE	yes		This is a very general parent term that is correct but not informative. The more specific term GO:0006083 (acetate metabolic process) properly identifies the specific organic acid metabolized.
METEA	ackA	IPR000890,IPR004372,IPR023865	GO:0016774	phosphotransferase activity, carboxyl group as acceptor	ACCEPT	no		"This accurately describes the enzymatic mechanism - AckA transfers a phosphate group from ATP to the carboxyl group of acetate. This is a more specific mechanistic description than the general kinase term. [file:METEA/ackA/ackA-uniprot.txt, ""acetate + ATP = acetyl phosphate + ADP""]. Falcon deep research describes this as a reversible phosphoryl transfer between acetate and ATP/ADP producing/consuming acetyl-phosphate."
METEA	ecm	IPR016176	GO:0003824	catalytic activity	MODIFY	yes	GO:0016866 intramolecular transferase activity	"The term ""catalytic activity"" is too general for a well-characterized enzyme. While there is no specific GO term for ""ethylmalonyl-CoA mutase activity"", the most appropriate existing term is GO:0016866 (intramolecular transferase activity), which accurately describes the mechanistic class of this enzyme. This is preferable to the overly broad ""catalytic activity"" and avoids the incorrect implication of ""methylmalonyl-CoA mutase activity"" which involves different substrates."
METEA	ecm	IPR006098	GO:0004494	methylmalonyl-CoA mutase activity	MODIFY	yes	GO:0016866 intramolecular transferase activity	Ecm is an ethylmalonyl-CoA mutase, not a methylmalonyl-CoA mutase. The substrates are different: ethylmalonyl-CoA vs methylmalonyl-CoA. UniProt clearly assigns EC 5.4.99.63 (ethylmalonyl-CoA mutase) to this enzyme based on PMID:25448820. There is no specific GO term for ethylmalonyl-CoA mutase activity, so the best option is to use the parent term GO:0016866 (intramolecular transferase activity) which is mechanistically accurate. A new GO term for ethylmalonyl-CoA mutase activity should be proposed.
METEA	ecm	IPR006099	GO:0016866	intramolecular transferase activity	ACCEPT	no		"The intramolecular transferase activity annotation accurately describes the mechanistic class of this enzyme. Given that there is no specific GO term for ""ethylmalonyl-CoA mutase activity"", GO:0016866 is the most informative and accurate term available. The enzyme belongs to EC 5.4.99.63, where 5.4 represents intramolecular transferases."
METEA	fae	IPR014826,IPR037075	GO:0016051	carbohydrate biosynthetic process	REMOVE	yes		Incorrect - While Fae works with H4MPT (which contains a pterin moiety), it does not participate in carbohydrate biosynthesis. Its function is formaldehyde activation for C1 metabolism.
METEA	fae	IPR014826,IPR037075	GO:0016840	carbon-nitrogen lyase activity	REMOVE	yes		This InterPro2GO (GO_REF:0000002) prediction is a misclassification. The falcon deep research and UniProt both establish the reaction as condensation of formaldehyde with H4MPT (a hydro-lyase, EC 4.2.1.147), not a carbon-nitrogen lyase. The correct MF is GO:0016836 (hydro-lyase activity), proposed as the replacement for the over-general GO:0016829 above.
METEA	fumC	IPR008948,IPR020557	GO:0003824	catalytic activity	KEEP_AS_NON_CORE	yes		This is an extremely general parent term for all enzymes. While technically correct, the specific term GO:0004333 (fumarate hydratase activity) provides precise functional annotation.
METEA	gcvH	IPR002930,IPR017453	GO:0005960	glycine cleavage complex	ACCEPT	no		Conserved family identity (GcvH family, GCS_H / lipoyl-binding domain) and authoritative reviews place GcvH as the H subunit of the four-protein glycine cleavage complex (P, T, L, H).
METEA	gcvP	IPR003437	GO:0006544	glycine metabolic process	KEEP_AS_NON_CORE	yes		Correct but too general; the specific child term GO:0019464 captures the actual process. Retained as non-core context. Falcon research confirms glycine as the substrate processed by GcvP.
METEA	gcvP	IPR020581	GO:0006546	glycine catabolic process	KEEP_AS_NON_CORE	yes		Correct but too general; the specific child term GO:0019464 better captures the glycine cleavage system process. Retained as non-core context.
METEA	gcvT	IPR006223	GO:0005960	glycine cleavage complex	ACCEPT	no		"GcvT is a component of the glycine cleavage complex, working together with gcvP, gcvH, and gcvL to catalyze the oxidative cleavage of glycine. This is the primary cellular location for the enzyme. [file:METEA/gcvT/gcvT-uniprot.txt, ""Glycine cleavage system T protein""]. Falcon deep research confirms GcvT (the T protein) functions with the GCS P, H, and L proteins, with the H protein carrying the lipoyl-bound aminomethyl intermediate that GcvT acts on."
METEA	gcvT	IPR006223	GO:0006546	glycine catabolic process	ACCEPT	no		"GcvT catalyzes the final step of glycine catabolism via the glycine cleavage system, transferring the aminomethyl group to THF and releasing ammonia. This connects glycine degradation to the one-carbon pool. [file:METEA/gcvT/gcvT-uniprot.txt, ""Glycine cleavage system T protein""]. Falcon deep research corroborates that by producing 5,10-methylene-THF, GcvT links glycine interconversion to the one-carbon folate pool, which in Methylorubrum extorquens AM1 feeds assimilation pathways including the serine cycle."
METEA	gltA	IPR010953	GO:0005737	cytoplasm	ACCEPT	no		"Citrate synthase is a cytoplasmic enzyme that functions in the TCA cycle. This is the primary cellular location for the enzyme. [file:METEA/gltA/gltA-uniprot.txt, ""C:cytoplasm""] The falcon deep research notes that this localization is a strong inference from bacterial biochemistry rather than directly demonstrated for AM1 GltA, as no direct subcellular localization experiment was retrieved."
METEA	gltA	IPR002020,IPR019810,IPR024176,IPR036969	GO:0046912	acyltransferase activity, acyl groups converted into alkyl on transfer	KEEP_AS_NON_CORE	yes		Mechanistically accurate parent term, but GO:0036440 (citrate synthase activity) is the specific child term that should serve as the core MF.
METEA	hprA	IPR006139,IPR006140	GO:0051287	NAD binding	ACCEPT	no		HprA requires NAD(P) as a cofactor and contains NAD(P)-binding Rossmann-fold domains for cofactor binding. This is a valid supporting molecular function consistent with membership in the D-isomer specific 2-hydroxyacid dehydrogenase family.
METEA	icd	IPR019818	GO:0000287	magnesium ion binding	ACCEPT	no		"Icd requires a divalent metal cation for catalysis, preferentially Mg2+ or Mn2+, binding one metal ion per subunit. Mg2+ is an essential cofactor. [file:METEA/icd/icd-uniprot.txt, ""Binds 1 Mg(2+) or Mn(2+) ion per subunit""]"
METEA	icd	IPR019818	GO:0016616	oxidoreductase activity, acting on the CH-OH group of donors, NAD or NADP as acceptor	ACCEPT	no		"This accurately describes the enzymatic mechanism - Icd is an oxidoreductase that acts on the CH-OH group of isocitrate, using NADP+ as the electron acceptor. Falcon deep research confirms the AM1 enzyme is NADP-dependent, with activity assayed by following NADPH production at 340 nm. [file:METEA/icd/icd-uniprot.txt, ""D-threo-isocitrate + NADP(+) = 2-oxoglutarate + CO2 + NADPH""]"
METEA	icd	IPR019818	GO:0051287	NAD binding	MODIFY	yes	GO:0050661 NADP binding	"This annotation is incorrect. Icd is an NADP-dependent enzyme that uses NADP+ as cofactor, not NAD+. The reaction clearly shows NADP(+) → NADPH. A more appropriate term would be NADP binding (GO:0050661), not NAD binding. Falcon deep research independently confirms the NADP-dependence of the M. extorquens AM1 enzyme via direct enzyme assays following NADPH production at 340 nm, supporting replacement of this NAD binding annotation with the NADP-specific term. [file:METEA/icd/icd-uniprot.txt, ""D-threo-isocitrate + NADP(+) = 2-oxoglutarate + CO2 + NADPH""; ""NADP""]"
METEA	lanM	IPR002048	GO:0005509	calcium ion binding	KEEP_AS_NON_CORE	yes		While LanM can bind calcium at high concentrations, this is not its physiological function. The primary role is lanthanide binding with exceptional selectivity. Deep research confirms ~10^8-fold preference for lanthanides over calcium, and that conserved EF-hand proline residues actively diminish calcium responsiveness, so the InterPro-derived calcium ion binding annotation reflects domain homology rather than physiological calcium binding.
METEA	mdcD	IPR017556	GO:0005975	carbohydrate metabolic process	KEEP_AS_NON_CORE	yes		Malonate catabolism produces acetate which enters central carbon metabolism, so there is an indirect connection to carbohydrate metabolism. However, this is not the core function of MdcD. The term is kept as non-core to reflect the connection to general carbon/energy metabolism without implying direct carbohydrate processing.
METEA	mdcD	IPR017556	GO:0016831	carboxy-lyase activity	ACCEPT	no		Carboxy-lyase activity (GO:0016831) is the appropriate general molecular function term for MdcD. The specific activity is malonyl-S-ACP decarboxylase (EC 4.1.1.87) which falls under the carboxy-lyase class. This annotation correctly captures the enzymatic class of MdcD.
METEA	mdh	IPR015955	GO:0003824	catalytic activity	KEEP_AS_NON_CORE	yes		This is an extremely general parent term for all enzymes. While technically correct, the specific term GO:0030060 (L-malate dehydrogenase activity) provides precise functional annotation.
METEA	mdh	IPR001557,IPR011275,IPR015955,IPR022383	GO:0016616	oxidoreductase activity, acting on the CH-OH group of donors, NAD or NADP as acceptor	ACCEPT	no		Accurate mechanistic parent term. The NAD-dependence underlying this term is directly supported by the AM1-specific crystallographic and kinetic study summarized in the falcon deep research (NAD+ bound in the structure; NADH used as reductant).
METEA	mdh	IPR001557	GO:0019752	carboxylic acid metabolic process	KEEP_AS_NON_CORE	yes		This is a very general parent term that is correct but not informative. Malate is a carboxylic acid, but more specific terms about TCA cycle would be more useful.
METEA	mllA	IPR007310,IPR037455	GO:0019290	siderophore biosynthetic process	KEEP_AS_NON_CORE	yes		The siderophore-biosynthesis term captures the correct enzyme family and pathway analogy but is iron-specific, whereas mllA contributes to a lanthanophore. Keep as non-core pending a lanthanophore biosynthetic process term.
METEA	mllBC	IPR007310,IPR037455	GO:0019290	siderophore biosynthetic process	KEEP_AS_NON_CORE	yes		The siderophore biosynthetic process term is defined for Fe(III)-chelating substances; methylolanthanin is a lanthanide chelator. The annotation is a useful analogy capturing the NIS biosynthetic role but is not species/process-precise, so it is retained as non-core pending a more specific (lanthanophore/metallophore) term.
METEA	mllH	IPR000182	GO:0016747	acyltransferase activity, transferring groups other than amino-acyl groups	MODIFY	yes	GO:0008080 N-acetyltransferase activity	The IEA term GO:0016747 is a correct but high-level parent. The protein carries a GNAT (GCN5-related N-acetyltransferase) domain and is predicted to acetylate a polyamine (homospermidine) amine, i.e. transfer an acetyl group to a nitrogen atom. The descendant term GO:0008080 (N-acetyltransferase activity) is therefore more informative and still consistent with the domain evidence. Substrate-specific terms (e.g. diamine N-acetyltransferase) are not used because the actual substrate is experimentally unresolved.
METEA	mllH		GO:0044550	secondary metabolite biosynthetic process	NEW	no		The mll cluster is experimentally required for methylolanthanin production and MllH is a predicted biosynthetic tailoring enzyme within it. secondary metabolite biosynthetic process (GO:0044550) is the most appropriate available BP term for lanthanophore biosynthesis; GO:0019290 (siderophore biosynthetic process) is explicitly inappropriate because methylolanthanin is a lanthanide chelator, not an Fe(III)-siderophore. This is a cluster-level/bioinformatic inference, not a gene-specific knockout result for mllH.
METEA	mluA	IPR010105	GO:0015343	siderophore-iron transmembrane transporter activity	MODIFY	yes	GO:0022857 transmembrane transporter activity	Wrong specificity but correct general activity. The protein is a TonB-dependent active uptake transporter, but the substrate is a lanthanide-metallophore, not an iron-siderophore. Rather than removing the transporter activity outright, generalize to transmembrane transporter activity (the iron-siderophore reaction defined for this term does not apply). The family-level uptake-transporter function is well supported; the precise ligand is not iron.
METEA	mluA	IPR010105	GO:0015891	siderophore transport	REMOVE	yes		Incorrect specificity. Siderophore transport is defined as movement of low-molecular-weight Fe(III)-chelating substances. This receptor is implicated in uptake of a lanthanide-metallophore complex (methylolanthanin), not an Fe(III) siderophore, so the term is inappropriate as an over-specific substrate assignment.
METEA	mluA	IPR011662	GO:0019867	outer membrane	KEEP_AS_NON_CORE	yes		Correct but less specific than the cell outer membrane annotation. The protein is an outer-membrane TonB-dependent beta-barrel transporter; the Gram-negative cell outer membrane term (GO:0009279) is preferred and is already ACCEPTed and used in core_functions. Keep this broader term as non-core because it is redundant with the more specific GO:0009279 for core representation.
METEA	mluA	IPR010105	GO:0038023	signaling receptor activity	KEEP_AS_NON_CORE	yes		Plausible and supported. TonB-dependent receptors of this signaling subtype possess an N-terminal signaling (Secretin/TonB short N-terminal) domain; for this protein the mll-cluster work describes a cell-surface signaling system in which the receptor interacts with the anti-sigma factor MluR upon ligand binding. Keep as a non-core signaling-receptor function alongside the core uptake-transport role; the review itself characterizes this as ancillary to the primary metal-chelate uptake-transport function.
METEA	mluI	IPR013249	GO:0003677	DNA binding	ACCEPT	no		ECF sigma factors recognize promoter DNA through their sigma4 domain (-35 element) when assembled with core RNA polymerase. DNA binding is consistent with the sigma-70/ECF family assignment, so the term is acceptable, though it is mechanistically subsumed by sigma factor activity (GO:0016987) for this protein.
METEA	mluI	IPR007627,IPR013249,IPR013325,IPR014284	GO:0003700	DNA-binding transcription factor activity	MARK_AS_OVER_ANNOTATED	yes		Over-annotation for a sigma factor. GO guidance separates the promoter- specificity role of sigma factors (GO:0016987 sigma factor activity) from sequence-specific DNA-binding transcription factor activity (GO:0003700), which describes regulators that bind cis-regulatory regions to modulate gene sets. The falcon report characterizes the primary biochemical role as transcription initiation specificity by binding core RNAP and directing it to cognate promoters - i.e. sigma factor activity, not generic DNA-binding TF activity. The InterPro2GO pipeline mis-applies the broad TF MF here.
METEA	mluI	IPR007627,IPR013249,IPR013325,IPR014284	GO:0006352	DNA-templated transcription initiation	ACCEPT	no		Correct. As an ECF sigma factor, mluI directs core RNA polymerase to initiate transcription from cognate promoters; this is the process counterpart of its sigma factor molecular function.
METEA	mxaB	IPR001789	GO:0000160	phosphorelay signal transduction system	ACCEPT	no		MxaB is a response regulator (receiver domain residues 17-134, conserved aspartate D67) component of the methanol-oxidation regulatory network. Falcon deep research supports a LuxR-like / orphan response-regulator architecture that may pair with the membrane histidine kinase MxaY in a non-traditional two-component system controlling the lanthanide switch. Domain-based, but consistent with the literature.
METEA	mxaB	IPR000792,IPR016032	GO:0006355	regulation of DNA-templated transcription	ACCEPT	no		MxaB is required for activation of the mxa operon (canonical mxaFJGIRSACKLDEHB) encoding the Ca2+-dependent methanol dehydrogenase system, acting as a positive transcriptional regulator. Falcon deep research provides direct AM1 evidence (Roszczenko-Jasinska et al.) and genome-annotation context (Chistoserdova et al., who list moxB/mxaB as a transcriptional regulator in cluster 1 / MOX), strengthening this annotation beyond the IEA domain inference.
METEA	mxaF	IPR017512	GO:0016020	membrane	MARK_AS_OVER_ANNOTATED	yes		Over-annotated. This bare membrane term adds no specific localization information. UniProt annotates MxaF as a peripheral inner-membrane protein on the periplasmic side, but the functionally informative location is the periplasmic space (GO:0030288), which is separately annotated. The generic membrane term should not be treated as core.
METEA	mxaF	IPR017512	GO:0016614	oxidoreductase activity, acting on CH-OH group of donors	KEEP_AS_NON_CORE	yes		Correct - MxaF oxidizes the CH-OH group of methanol (a primary alcohol) to formaldehyde. This is an accurate but intermediate-specificity parent of GO:0052933; keep as non-core since the cytochrome c(L)-coupled child term is more informative.
METEA	mxaF	IPR001479	GO:0030288	outer membrane-bounded periplasmic space	ACCEPT	no		Correct - MxaF performs methanol oxidation in the periplasm. This is the functionally relevant subcellular location and is a core localization for the gene product.
METEA	mxaG	IPR009153	GO:0005506	iron ion binding	ACCEPT	no		The heme c iron is the redox-active center of cytochrome c_L; iron ion binding is a correct molecular function supported by the UniProt covalent heme c binding sites and the Fe axial-binding residue.
METEA	mxaG	IPR009056,IPR009153,IPR036909	GO:0009055	electron transfer activity	ACCEPT	no		This is the primary molecular function of the gene product. Multiple authoritative sources name MxaG as the cytochrome c_L electron-transfer partner of methanol dehydrogenase, transferring electrons from PQQ to downstream cytochromes.
METEA	mxaG	IPR009056,IPR009153,IPR036909	GO:0020037	heme binding	ACCEPT	no		Covalent heme c binding is documented in UniProt (CXXCH-type c-type cytochrome with covalent thioether attachment at residues 90 and 93 and Fe axial coordination at residue 94); the heme is essential to its electron-transfer function.
METEA	mxaI	IPR003420,IPR036557	GO:0004022	alcohol dehydrogenase (NAD+) activity	REMOVE	yes		"Incorrect - MxaI is a non-catalytic structural subunit that does not possess enzymatic activity, and the catalytic activity resides entirely in MxaF [file:METEA/mxaI/mxaI-claude-deep-research.md, ""MxaI does not directly participate in substrate binding or catalysis""]. Additionally, this InterPro-derived term is doubly wrong because the MxaFI methanol dehydrogenase is a PQQ/Ca2+-dependent quinoprotein that donates electrons to cytochrome c(L), not an NAD+-dependent alcohol dehydrogenase (UniProt EC 1.1.2.7). Falcon deep research confirms MxaI contributes structurally rather than forming the catalytic active site."
METEA	mxaI	IPR003420,IPR036557	GO:0015946	methanol oxidation	ACCEPT	no		Correct - MxaI is a structural subunit of the MxaFI enzyme complex that oxidizes methanol to formaldehyde in the periplasm. Falcon deep research confirms that the MxaFI holoenzyme catalyzes the oxidation of methanol to formaldehyde, with MxaI contributing structurally rather than forming the catalytic active site itself.
METEA	mxaJ	IPR022455	GO:0046170	methanol catabolic process	ACCEPT	no		MxaJ is an accessory factor in the periplasmic methanol oxidation module; its chaperone role in producing active MxaFI directly supports methanol catabolism. This term is preferred over the broader GO:0015945.
METEA	mxbD	IPR003661,IPR036097	GO:0000155	phosphorelay sensor kinase activity	ACCEPT	no		Correct. MxbD is the sensor histidine kinase of the MxbDM two-component system; it carries the HisKA dimerization/phospho-acceptor and HATPase_c catalytic domains characteristic of phosphorelay sensor kinases and acts with the cognate response regulator MxbM. The deep-research synthesis consistently identifies MxbD as the sensor histidine kinase component of MxbDM. Note that direct biochemical demonstration of phosphotransfer in AM1 has not been reported (regulatory role is supported by genetics/reporters), but the sensor histidine kinase assignment is well supported by domain architecture and modular-sensor engineering studies.
METEA	mxbD	IPR003660,IPR003661,IPR036097	GO:0007165	signal transduction	ACCEPT	no		Correct. As the sensor kinase of the MxbDM two-component system, MxbD transduces a signal (whose precise identity in AM1 is unresolved) to control transcription of methanol oxidation genes, contributing to the lanthanide-responsive switch between the mxa and xox1 systems. The native input signal (lanthanides directly, methanol/formaldehyde, XoxF metal status, or another cue) remains an open question.
METEA	mxbD	IPR004358	GO:0016772	transferase activity, transferring phosphorus-containing groups	ACCEPT	no		Correct but general. Parent of histidine kinase activity (transfers phosphate from ATP to a histidine residue, then to the MxbM response regulator). The specific MF terms GO:0004673 and GO:0000155 are preferred. Retained as a true but high-level parent.
METEA	mxcE	IPR001789	GO:0000160	phosphorelay signal transduction system	ACCEPT	no		Correct - MxcE is the response regulator of the MxcQE two-component system, receiving phosphoryl groups from the MxcQ sensor kinase on a conserved aspartate in its N-terminal receiver domain and modulating downstream transcription. This is well supported by both domain architecture (UniProt Response regulatory domain 21-138; 4-aspartylphosphate at residue 71) and the literature.
METEA	mxcE	IPR000792,IPR016032	GO:0006355	regulation of DNA-templated transcription	ACCEPT	no		Correct - MxcE functions as a transcriptional activator within the methanol-oxidation regulatory cascade. It activates expression from the mxbDM promoter, which in turn controls expression of the mxa (Ca-dependent methanol dehydrogenase) operon. mxcE mutants show altered transcriptional output at methylotrophy promoters.
METEA	mxcQ	IPR011712	GO:0000155	phosphorelay sensor kinase activity	ACCEPT	no		"Correct - MxcQ is the sensor histidine kinase of the MxcQE two-component system, autophosphorylating on a conserved histidine residue and transferring the phosphate to the MxcE response regulator. Falcon deep research independently confirms this organism-specific role, noting MxcQ is ""part of the MxcQE two-component system"" and is ""annotated as a histidine kinase (EC 2.7.13.3 in UniProt)"" [file:METEA/mxcQ/mxcQ-deep-research-falcon.md]."
METEA	mxcQ	IPR003660	GO:0007165	signal transduction	KEEP_AS_NON_CORE	yes		Correct but very general parent term - More specific phosphorelay signal transduction term better describes MxcQ's function.
METEA	mxcQ	IPR004358	GO:0016772	transferase activity, transferring phosphorus-containing groups	KEEP_AS_NON_CORE	yes		Correct but general - MxcQ transfers phosphate groups from ATP to histidine and then to aspartate on MxcE, but more specific kinase terms better describe this activity.
METEA	mxcQ	IPR011712	GO:0046983	protein dimerization activity	ACCEPT	no		"Likely correct - Histidine kinases typically function as homodimers with the four-helix bundle domain forming coiled-coil dimers [file:METEA/mxcQ/mxcQ-claude-deep-research.md, ""four-helix bundle typically exists as a homodimer""]."
METEA	pckA	IPR008210,IPR013035	GO:0004611	phosphoenolpyruvate carboxykinase activity	KEEP_AS_NON_CORE	yes		This is a general term for PEPCK activity. However, the more specific term GO:0004612 (phosphoenolpyruvate carboxykinase (ATP) activity) properly distinguishes the ATP-dependent bacterial enzyme from the GTP-dependent eukaryotic form.
METEA	pckA	IPR008210,IPR013035	GO:0017076	purine nucleotide binding	ACCEPT	no		PckA binds ATP (a purine nucleotide) as a substrate for the phosphorylation reaction. This is a valid supporting molecular function, though GO:0005524 (ATP binding) is more specific.
METEA	pqqE	IPR000385,IPR007197	GO:0003824	catalytic activity	KEEP_AS_NON_CORE	yes		Subsumed by the more specific MF GO:0009975 (cyclase activity); retained as non-core because it does not convey the actual reaction.
METEA	serA	IPR006139	GO:0016616	oxidoreductase activity, acting on the CH-OH group of donors, NAD or NADP as acceptor	ACCEPT	no		This accurately describes the enzymatic mechanism - SerA oxidizes the hydroxyl group at C-2 of 3-phosphoglycerate using NAD+ as electron acceptor. Consistent with the D-isomer specific 2-hydroxyacid dehydrogenase chemistry, a stereospecific reversible redox transformation of 2-keto/2-hydroxy acids with NAD(P).
METEA	serA	IPR006139,IPR006140	GO:0051287	NAD binding	ACCEPT	no		SerA requires NAD+ as a cofactor for its dehydrogenase activity and contains a NAD(P)-binding Rossmann-fold domain. This is a valid supporting molecular function. Supported by InterPro IPR006139/IPR006140 and the SUPFAM Rossmann-fold assignment in UniProt.
METEA	xoxF1	IPR017512	GO:0016020	membrane	REMOVE	yes		"INCORRECT. XoxF1 is a periplasmic protein, not membrane-bound. The N-terminal signal peptide directs the protein to the periplasm via the Sec pathway, where it is cleaved. While it may loosely associate with the membrane surface, the proper cellular component annotation is ""periplasmic space"" (GO:0042597), not membrane. Falcon deep research consistently describes XoxF1 as periplasmic."
METEA	xoxF1	IPR017512	GO:0016614	oxidoreductase activity, acting on CH-OH group of donors	ACCEPT	no		CORRECT - CORE FUNCTION. This is a specific molecular function term for XoxF1. The enzyme specifically oxidizes the CH-OH group of methanol (primary alcohol) to formaldehyde (aldehyde). This term accurately captures the specific chemistry of the catalytic reaction, although the even more specific GO:0052933 (alcohol dehydrogenase, cytochrome c(L) activity) best captures the electron acceptor.
METEA	xoxF1	IPR001479	GO:0030288	outer membrane-bounded periplasmic space	ACCEPT	no		CORRECT. Accurate description of the periplasmic localization in Gram-negative bacteria. The N-terminal signal peptide (residues 1-21) directs XoxF1 to the periplasm, where it functions between the inner and outer membranes.
METEA	xoxG	IPR009056,IPR036909	GO:0009055	electron transfer activity	ACCEPT	no		Correct - XoxG is the physiological electron acceptor that accepts electrons from reduced XoxF (lanthanide-dependent methanol dehydrogenase) following methanol oxidation and transfers them onward into the respiratory electron transport chain. This is the core molecular function of XoxG and is strongly supported by direct biochemistry.
METEA	xoxG	IPR009056,IPR036909	GO:0020037	heme binding	ACCEPT	no		Correct - XoxG is a c-type cytochrome carrying a covalently bound heme c attached via the canonical CXXCH motif (Cys95/Cys98). Heme binding is essential for its electron-transfer function.
METJA	nadX	IPR005106	GO:0016491	oxidoreductase activity	MODIFY	yes	GO:0033735 L-aspartate dehydrogenase [NAD(P)+] activity	GO:0016491 (oxidoreductase activity) is far too general; GO:0033735 provides the precise molecular function. This is a typical InterPro2GO limitation where domain-level annotation yields only broad functional categories.
METJA	thiL	IPR006283	GO:0009228	thiamine biosynthetic process	KEEP_AS_NON_CORE	yes		ThiL is part of the overall thiamine biosynthetic pathway, so this annotation is not incorrect. However, it is less specific than GO:0009229 (thiamine diphosphate biosynthetic process), which directly describes the step ThiL catalyzes. The more specific term is already annotated. This broader term is retained as non-core since it provides useful pathway context via InterPro2GO but does not capture the precise biological role.
METJA	thiL		GO:0005737	cytoplasm	NEW	no		ThiL is a soluble enzyme that acts on cytoplasmic substrates (ATP and TMP). The protein has no transmembrane domains, signal peptides, or other localization signals. Cytoplasmic localization is consistent with its enzymatic role in the thiamine biosynthetic pathway, where substrates and products are cytoplasmic metabolites. Although no direct experimental localization data exists for this archaeal protein, the inference is strong based on protein architecture and pathway context.
METTP	gatC	IPR003837,IPR036113	GO:0006450	regulation of translational fidelity	ACCEPT	no		This annotation is supported by recent evidence from Mycobacterium tuberculosis showing that GatCAB functions as a modulator of translational fidelity, with reduced GatCAB activity leading to increased mistranslation. The GatCAB complex ensures accurate incorporation of glutamine at glutamine codons, directly contributing to translational fidelity.
MISSI	APQ	IPR000425	GO:0015267	channel activity	MODIFY	yes	GO:0015250 water channel activity	Use the substrate-specific water channel activity term for this aquaporin-family membrane channel.
MISSI	APQ	IPR000425	GO:0055085	transmembrane transport	MODIFY	yes	GO:0006833 water transport	The aquaporin family assignment supports water transport as the more informative process.
MISSI	CAD	IPR020843	GO:0016491	oxidoreductase activity	MODIFY	yes	GO:0045551 cinnamyl-alcohol dehydrogenase activity	The UniProt entry provides EC 1.1.1.195 and specific cinnamyl/coniferyl alcohol dehydrogenase reactions.
MISSI	CAD	IPR047109	GO:0016616	oxidoreductase activity, acting on the CH-OH group of donors, NAD or NADP as acceptor	MODIFY	yes	GO:0045551 cinnamyl-alcohol dehydrogenase activity	The substrate-specific CAD term better captures the annotated EC 1.1.1.195 reactions.
MISSI	COMT	IPR016461	GO:0008168	methyltransferase activity	MODIFY	yes	GO:0047763 caffeate O-methyltransferase activity	Replace the generic parent with the specific EC/Rhea-supported caffeate O-methyltransferase activity annotation.
MISSI	COMT	IPR001077	GO:0008171	O-methyltransferase activity	MODIFY	yes	GO:0047763 caffeate O-methyltransferase activity	The UniProt catalytic reaction and EC 2.1.1.68 support the more specific caffeate O-methyltransferase activity.
MISSI	COMT	IPR012967	GO:0046983	protein dimerization activity	KEEP_AS_NON_CORE	yes		Retain as non-core because caffeate O-methyltransferase activity captures the main molecular role.
MISSI	LHS1	IPR002100,IPR036879	GO:0003677	DNA binding	MARK_AS_OVER_ANNOTATED	yes		The MADS-box/K-box domain evidence supports DNA-binding transcription factor activity; retaining the broad DNA binding parent as core would be redundant.
MISSI	LHS1	IPR002487	GO:0003700	DNA-binding transcription factor activity	ACCEPT	no		The protein is a MADS-box/K-box transcription factor fragment, and InterPro supports the DNA-binding transcription factor annotation.
MISSI	LHS1	IPR002487	GO:0006355	regulation of DNA-templated transcription	ACCEPT	no		The annotation follows from the supported MADS-box/K-box transcription factor domains and nuclear localization.
MISSI	LHS1	IPR002100,IPR036879	GO:0046983	protein dimerization activity	KEEP_AS_NON_CORE	yes		MADS/K-box transcription factors commonly dimerize, and InterPro supports this annotation, but the core function is transcriptional regulation.
MISSI	MnSOD	IPR001189,IPR019831,IPR019832,IPR019833	GO:0006801	superoxide metabolic process	KEEP_AS_NON_CORE	yes		This broader process term is correct but less specific than GO:0019430 for MnSOD's core role.
MISSI	MnSOD	IPR001189,IPR019831,IPR019832,IPR019833	GO:0046872	metal ion binding	KEEP_AS_NON_CORE	yes		The specific manganese ion binding annotation should represent the core cofactor-binding aspect; the parent metal-binding term is non-core.
MOOTH	acsD	IPR004486	GO:0006730	one-carbon metabolic process	ACCEPT	no		This annotation accurately captures a core function of AcsD. The protein specifically handles one-carbon units (methyl groups) as part of the Wood-Ljungdahl pathway, transferring them from 5-methyl-H4folate to acetyl-CoA synthase via its corrinoid cofactor. This is well-supported by structural and biochemical evidence from PMID:22419154.
MYCTU	clpP2	IPR001907	GO:0004176	ATP-dependent peptidase activity	ACCEPT	no		Correct InterPro2GO mapping. IPR001907 is the ClpP protease family, and ATP-dependent peptidase activity is the appropriate molecular function for this family. Supported by the same biochemical evidence as the IBA annotation.
NICAT	NaA622	IPR045312	GO:0016491	oxidoreductase activity	MARK_AS_OVER_ANNOTATED	yes		The glucosylation preprint resolves A622 as a specific late-pathway reductase acting on nicotinic acid N-glucoside, so the broad parent term no longer captures the informative chemistry of the protein.
NICAT	NaA622_candidate_IFRH_0	IPR045312	GO:0016491	oxidoreductase activity	ACCEPT	no		The accession clearly belongs to the oxidoreductase-like A622 family, even though its exact pathway placement relative to the primary A622 mapping is still unresolved.
NICAT	NaAO2_candidate_AO_0	IPR015939,IPR037099	GO:0016491	oxidoreductase activity	MARK_AS_OVER_ANNOTATED	yes		The more informative catalytic term GO:0008734 already captures the actual chemistry of AO_0.
NICAT	NaAO2_candidate_AO_1	IPR015939,IPR037099	GO:0016491	oxidoreductase activity	MARK_AS_OVER_ANNOTATED	yes		GO:0008734 already captures the informative chemistry for this candidate.
NICAT	NaBBL1_candidate_FOX1_0	IPR012951	GO:0016491	oxidoreductase activity	MARK_AS_OVER_ANNOTATED	yes		The BBL family is now tied to a specific late oxidative step in nicotine synthesis, so the parent oxidoreductase term is no longer the most useful annotation.
NICAT	NaBBL1_candidate_FOX1_0	IPR006094,IPR012951,IPR036318	GO:0050660	flavin adenine dinucleotide binding	ACCEPT	no		BBL-family late oxidases are flavoproteins, and UniProt explicitly assigns FAD cofactor use.
NICAT	NaBBL1_candidate_FOX1_0	IPR016166	GO:0071949	FAD binding	REMOVE	yes		Keep the more standard GO:0050660 flavin adenine dinucleotide binding term and drop the redundant duplicate.
NICAT	NaBBL2_candidate_FOX1_2	IPR012951	GO:0016491	oxidoreductase activity	MARK_AS_OVER_ANNOTATED	yes		The BBL family is now tied to a specific late nicotine oxidase role, so the parent term is not the most informative curation outcome.
NICAT	NaBBL2_candidate_FOX1_2	IPR006094,IPR012951,IPR036318	GO:0050660	flavin adenine dinucleotide binding	ACCEPT	no		BBL-family proteins are FAD-linked oxidoreductases, and this cofactor term is informative and specific.
NICAT	NaBBL2_candidate_FOX1_2	IPR016166	GO:0071949	FAD binding	REMOVE	yes		Keep GO:0050660 as the preferred cofactor-binding annotation and drop the duplicate variant.
NICAT	NaBBL_candidate_FOX1_4	IPR012951	GO:0016491	oxidoreductase activity	MARK_AS_OVER_ANNOTATED	yes		BBL-family proteins are now linked to a specific late nicotine oxidation role rather than only generic redox chemistry.
NICAT	NaBBL_candidate_FOX1_4	IPR006094,IPR012951,IPR036318	GO:0050660	flavin adenine dinucleotide binding	ACCEPT	no		The BBL family is FAD linked, making this a useful and specific cofactor annotation.
NICAT	NaBBL_candidate_FOX1_4	IPR016166	GO:0071949	FAD binding	REMOVE	yes		Keep the more explicit flavin adenine dinucleotide binding term and remove the redundant duplicate.
NICAT	NaBBL_candidate_FOX2_2	IPR012951	GO:0016491	oxidoreductase activity	MARK_AS_OVER_ANNOTATED	yes		BBL-family proteins are now tied to a specific late oxidation role in nicotine synthesis.
NICAT	NaBBL_candidate_FOX2_2	IPR006094,IPR012951,IPR036318	GO:0050660	flavin adenine dinucleotide binding	ACCEPT	no		This is an informative cofactor annotation for a BBL-family oxidoreductase.
NICAT	NaBBL_candidate_FOX2_2	IPR016166	GO:0071949	FAD binding	REMOVE	yes		Use GO:0050660 as the preferred cofactor-binding term and drop the redundant duplicate.
NICAT	NaBBL_candidate_FOX2_4	IPR012951	GO:0016491	oxidoreductase activity	MARK_AS_OVER_ANNOTATED	yes		BBL-family proteins now have a more specific late nicotine oxidation role than this parent term conveys.
NICAT	NaBBL_candidate_FOX2_4	IPR006094,IPR012951,IPR036318	GO:0050660	flavin adenine dinucleotide binding	ACCEPT	no		This is an informative and specific term for a BBL-family flavoprotein.
NICAT	NaBBL_candidate_FOX2_4	IPR016166	GO:0071949	FAD binding	REMOVE	yes		Retain GO:0050660 as the preferred cofactor-binding term and remove the duplicate.
NICAT	NaBGL1_candidate_BGLU18_6	IPR001360	GO:0005975	carbohydrate metabolic process	MARK_AS_OVER_ANNOTATED	yes		The more informative biology is a nicotine-pathway glucoside hydrolase role rather than generic carbohydrate metabolism.
NICAT	NaBGL1_candidate_BGLU42	IPR001360	GO:0004553	hydrolase activity, hydrolyzing O-glycosyl compounds	MODIFY	yes	GO:0008422 beta-glucosidase activity	GO:0008422 already captures the relevant glycosidase specificity for this GH1 family enzyme.
NICAT	NaBGL1_candidate_BGLU42	IPR001360	GO:0005975	carbohydrate metabolic process	MARK_AS_OVER_ANNOTATED	yes		The evidence that remains secure for this accession is generic GH1 beta-glucosidase chemistry rather than a specific pathway assignment.
NICAT	NaBGL1_candidate_BGLU42	IPR017736	GO:0030245	cellulose catabolic process	REMOVE	yes		This appears to be a generic GH1 family overcall rather than a reviewed biological role for BGLU42.
NICAT	NaBGL2_candidate_BGLU18_1	IPR001360	GO:0005975	carbohydrate metabolic process	MARK_AS_OVER_ANNOTATED	yes		The important curation question is whether this copy participates in late nicotine-pathway glucoside hydrolysis, not generic carbohydrate metabolism.
NICAT	NaMATE1_candidate_DTX40_3	IPR002528	GO:0015297	antiporter activity	ACCEPT	no		The current public evidence clearly supports a MATE-family antiporter even though the exact specialized substrate remains unresolved.
NICAT	NaMATE1_candidate_DTX40_3	IPR002528,IPR045069	GO:0042910	xenobiotic transmembrane transporter activity	UNDECIDED	yes		Current evidence points toward a specialized nicotine-module transporter role, but the exact transported metabolite remains experimentally unresolved. Because MATE transporters often move alkaloids and other secondary metabolites, the nicotine-pathway placement does not by itself falsify a xenobiotic transmembrane transporter annotation.
NICAT	NaMATE1_candidate_DTX40_3	IPR002528	GO:0055085	transmembrane transport	KEEP_AS_NON_CORE	yes		Keep the transport process annotation while prioritizing the antiporter function and pathway-specific interpretation.
NICAT	NaMATE1_candidate_DTX40_3	IPR045069	GO:1990961	xenobiotic detoxification by transmembrane export across the plasma membrane	UNDECIDED	yes		The reviewed evidence supports a pathway-associated metabolite transporter, but it does not identify the transported substrate or establish whether export across the plasma membrane is the relevant compartment. A nicotine- related substrate could still fit a xenobiotic-detoxification framing, so this process annotation should remain undecided pending direct transport and localization assays.
NICAT	NaMPO1_candidate_AMO_3	IPR000269,IPR015798,IPR015800,IPR015802,IPR016182,IPR036460	GO:0048038	quinone binding	KEEP_AS_NON_CORE	yes		Topaquinone chemistry is relevant to catalytic mechanism, but it is a secondary conclusion relative to the pathway reaction itself.
NICAT	NaODC_candidate_DCOR	IPR000183,IPR009006,IPR022643,IPR022644	GO:0003824	catalytic activity	MARK_AS_OVER_ANNOTATED	yes		GO:0004586 already captures the specific chemistry of the DCOR candidate.
NICAT	NaODC_candidate_DCOR	IPR002433	GO:0006596	polyamine biosynthetic process	ACCEPT	no		Ornithine decarboxylase chemistry directly feeds polyamine biosynthesis via putrescine formation.
NICAT	NaODC_candidate_ODC	IPR000183,IPR009006,IPR022644	GO:0003824	catalytic activity	MARK_AS_OVER_ANNOTATED	yes		GO:0004586 already captures the informative enzymatic chemistry for this accession.
NICAT	NaODC_candidate_ODC	IPR002433	GO:0006596	polyamine biosynthetic process	ACCEPT	no		Ornithine decarboxylase provides putrescine to the polyamine pathway.
NICAT	NaPMT1.1	IPR001045	GO:0003824	catalytic activity	MARK_AS_OVER_ANNOTATED	yes		GO:0030750 putrescine N-methyltransferase activity captures the actual chemistry; the generic catalytic parent term adds no useful biological resolution.
NICAT	NaPMT1.2	IPR001045	GO:0003824	catalytic activity	MARK_AS_OVER_ANNOTATED	yes		GO:0030750 putrescine N-methyltransferase activity already captures the actual chemistry performed by PMT2.
NICAT	NaPMT3	IPR001045	GO:0003824	catalytic activity	MARK_AS_OVER_ANNOTATED	yes		GO:0030750 already captures the specific methyltransferase chemistry of PMT3.
NICAT	NaQPT2_candidate_QPT_0	IPR022412,IPR037128	GO:0016763	pentosyltransferase activity	MODIFY	yes	GO:0004514 nicotinate-nucleotide diphosphorylase (carboxylating) activity	GO:0004514 already captures the exact catalytic chemistry for this protein.
NICAT	NaQPT2_candidate_QPT_1	IPR022412,IPR037128	GO:0016763	pentosyltransferase activity	MODIFY	yes	GO:0004514 nicotinate-nucleotide diphosphorylase (carboxylating) activity	QPT_1 has a specific phosphoribosyltransferase annotation that should be preferred over the generic pentosyltransferase parent.
NICAT	NaUGT1_candidate_UGT85A2_0	IPR002213	GO:0008194	UDP-glycosyltransferase activity	MODIFY	yes	GO:0035251 UDP-glucosyltransferase activity	GO:0035251 is the better currently available parent for the glucosyltransferase chemistry implicated in the nicotine pathway.
OCTBM	CRT1	IPR006201	GO:0004888	transmembrane signaling receptor activity	MODIFY	yes	GO:0099094 ligand-gated monoatomic cation channel activity	While CRT1 is indeed a transmembrane receptor, this IEA annotation from InterPro is too general. CRT1 functions specifically as a ligand-gated cation channel rather than a generic signaling receptor. The more precise term GO:0099094 (ligand-gated monoatomic cation channel activity) better captures the experimentally demonstrated ionotropic mechanism.
OCTBM	CRT1	IPR006201	GO:0005216	monoatomic ion channel activity	ACCEPT	no		Ion channel activity is a core function of CRT1, directly demonstrated by electrophysiology showing cation permeation upon ligand binding. While the more specific child term GO:0005230 (extracellular ligand-gated monoatomic ion channel activity) is also annotated, this broader parent term is acceptable as a companion IEA annotation.
OCTBM	CRT1	IPR006202,IPR036734	GO:0005230	extracellular ligand-gated monoatomic ion channel activity	ACCEPT	no		This is the most specific and accurate MF annotation for CRT1. The cryo-EM structure (PDB:8EIS) confirms the extracellular ligand-binding domain and the directly coupled transmembrane ion pore. Electrophysiology demonstrates ligand-gated channel opening with minimal desensitization. This is a core molecular function.
OCTBM	CRT1	IPR006029,IPR006202,IPR036719,IPR036734	GO:0006811	monoatomic ion transport	ACCEPT	no		Ion transport is a core function of CRT1. While GO:0034220 is more specific, this broader parent term is fine as a companion IEA annotation from InterPro.
OCTBM	CRT1	IPR006201	GO:0034220	monoatomic ion transmembrane transport	ACCEPT	no		This is a well-supported BP annotation. Transmembrane ion transport is a direct consequence of CRT1 channel opening and is essential for signal transduction in chemosensory cells. Electrophysiology in both native sucker cells and heterologous expression systems confirms cation permeation.
OCTBM	OCBIM_22006518mg	IPR006201	GO:0004888	transmembrane signaling receptor activity	MODIFY	yes	GO:0099094 ligand-gated monoatomic cation channel activity	While CRT1 is indeed a transmembrane receptor, this IEA annotation from InterPro is too general. CRT1 functions specifically as a ligand-gated cation channel rather than a generic signaling receptor. The more precise term GO:0099094 (ligand-gated monoatomic cation channel activity) better captures the experimentally demonstrated ionotropic mechanism.
OCTBM	OCBIM_22006518mg	IPR006201	GO:0005216	monoatomic ion channel activity	ACCEPT	no		Ion channel activity is a core function of CRT1, directly demonstrated by electrophysiology showing cation permeation upon ligand binding. While the more specific child term GO:0005230 (extracellular ligand-gated monoatomic ion channel activity) is also annotated, this broader parent term is acceptable as a companion IEA annotation.
OCTBM	OCBIM_22006518mg	IPR006202,IPR036734	GO:0005230	extracellular ligand-gated monoatomic ion channel activity	ACCEPT	no		This is the most specific and accurate MF annotation for CRT1. The cryo-EM structure (PDB:8EIS) confirms the extracellular ligand-binding domain and the directly coupled transmembrane ion pore. Electrophysiology demonstrates ligand-gated channel opening with minimal desensitization. This is a core molecular function.
OCTBM	OCBIM_22006518mg	IPR006029,IPR006202,IPR036719,IPR036734	GO:0006811	monoatomic ion transport	ACCEPT	no		Ion transport is a core function of CRT1. While GO:0034220 is more specific, this broader parent term is fine as a companion IEA annotation from InterPro.
OCTBM	OCBIM_22006518mg	IPR006201	GO:0034220	monoatomic ion transmembrane transport	ACCEPT	no		This is a well-supported BP annotation. Transmembrane ion transport is a direct consequence of CRT1 channel opening and is essential for signal transduction in chemosensory cells. Electrophysiology in both native sucker cells and heterologous expression systems confirms cation permeation.
OCTBM	OCBIM_22008529mg		GO:0005335	serotonin:sodium:chloride symporter activity	NEW	no		This TreeGrafter annotation from UniProt correctly identifies the core molecular activity of this protein but is not yet in QuickGO GOA. SERT/SLC6A4 is definitively a serotonin:sodium:chloride symporter based on its clear orthology to human SERT, conservation of key binding residues, PANTHER subfamily assignment (PTHR11616:SF279), and the SNF domain (PF00209). The pharmacological evidence from Edsinger and Dolen (2018) showing MDMA binding to this transporter further supports this assignment.
OCTBM	OCBIM_22008529mg		GO:0051378	serotonin binding	NEW	no		Serotonin binding is a core function of SERT required for its transport activity. This annotation from UniProt TreeGrafter is not yet in QuickGO GOA. The conservation of the binding site was confirmed through phylogenomic analysis of the MDMA binding pocket [PMID:30245101].
OCTBM	OCBIM_22008529mg		GO:0046872	metal ion binding	NEW	no		"Metal ion (sodium) binding is mechanistically required for SERT function. However, ""metal ion binding"" is too generic to convey meaningful functional information. The symporter activity annotation (GO:0005335) already captures the Na+ dependence. Including as a non-core supporting annotation only."
OCTBM	OCBIM_22008529mg		GO:0043005	neuron projection	NEW	no		Neuron projection localization is expected for a presynaptic serotonin reuptake transporter. Serotonin-containing neurons have been identified in cephalopod nervous systems, and SERT function requires localization to neuronal membranes at or near synapses.
OCTBM	OCBIM_22008529mg		GO:0005886	plasma membrane	NEW	no		Plasma membrane localization is an essential aspect of SERT function. The protein must be at the cell surface to perform serotonin reuptake from the synaptic cleft. UniProt annotates this via ARBA rules.
OCTBM	OCBIM_22008529mg		GO:0098793	presynapse	NEW	no		Presynaptic localization is the canonical location for neurotransmitter reuptake transporters. This is a well-supported annotation by homology, consistent with the demonstrated pharmacological role of octopus SERT.
OCTVU	CTR1	IPR000276,IPR001817,IPR017452	GO:0016020	membrane	ACCEPT	no		Correct but generic. This IEA annotation from InterPro is subsumed by the more specific plasma membrane annotation. Acceptable to retain as a broad IEA annotation.
OCTVU	CTR2	IPR000276,IPR001817,IPR017452	GO:0016020	membrane	ACCEPT	no		Correct but redundant with the more specific GO:0005886 (plasma membrane) annotation. As an IEA from InterPro2GO mapping, it is acceptable to retain. Consistent with CTR1 and OPR reviews.
OCTVU	DDO	IPR023209	GO:0046416	D-amino acid metabolic process	KEEP_AS_NON_CORE	yes		This is a valid but more general parent of GO:0019478 (D-amino acid catabolic process). Since the more specific catabolic term is already annotated with IDA evidence, this broader term adds minimal information but is not wrong. Kept as non-core.
OCTVU	DDO	IPR023209	GO:0071949	FAD binding	ACCEPT	no		FAD binding is experimentally established. DDO is a flavoenzyme containing stoichiometric FAD as cofactor [PMID:7915543]. This IEA is consistent with the IDA annotation for the same term.
OCTVU	OPR	IPR000276,IPR001817,IPR017452	GO:0016020	membrane	ACCEPT	no		This is correct but redundant with the more specific GO:0005886 (plasma membrane) annotation. However, as an IEA from InterPro2GO mapping, it is acceptable to retain. The protein has 7 predicted transmembrane helices and is clearly membrane-associated.
ORYSJ	CCAMK	IPR000719,IPR008271	GO:0004672	protein kinase activity	ACCEPT	no		Correct but a broad parent term. OsCCaMK/OsDMI3 is an active serine/threonine protein kinase (EC 2.7.11.17) whose kinase domain (residues 13-298) and ATP-binding/active-site residues are annotated in UniProt, and rice OsDMI3 kinase activity has been assayed directly [file:ORYSJ/CCAMK/CCAMK-deep-research-falcon.md]. The more informative, specific MF (calcium/calmodulin-dependent protein kinase activity, GO:0004683) is also annotated; the generic parent is not wrong and can be accepted.
ORYSJ	CCAMK	IPR002048	GO:0005509	calcium ion binding	ACCEPT	no		Correct and core. UniProt annotates three EF-hand domains (residues ~392-505) with numerous Ca2+-coordinating BINDING residues, and CCaMK/DMI3 proteins are described as having C-terminal EF-hand Ca2+-binding motifs that enable regulation by Ca2+ signatures [file:ORYSJ/CCAMK/CCAMK-deep-research-falcon.md]. Calcium binding via the EF-hands is mechanistically central to the kinase's role as a Ca2+ decoder.
ORYSJ	CCAMK	IPR000719,IPR017441	GO:0005524	ATP binding	ACCEPT	no		Correct. UniProt annotates an ATP-binding region (residues 19-27) and an ATP-binding residue (43) in the kinase domain, consistent with the kinase mechanism (transfer of phosphate from ATP to protein Ser/Thr residues) [file:ORYSJ/CCAMK/CCAMK-deep-research-falcon.md]. ATP binding is an obligatory cofactor-binding function for the kinase activity.
ORYSJ	CKX2	IPR016164	GO:0003824	catalytic activity	MODIFY	yes	GO:0019139 cytokinin dehydrogenase activity	"""Catalytic activity"" is the top-level molecular-function grouping term and carries no information about what reaction OsCKX2 catalyses. The specific catalytic function - cytokinin dehydrogenase/oxidase activity (EC 1.5.99.12) - is demonstrated directly [PMID:15976269] and is annotated elsewhere in this review (GO:0019139). The annotation should be modified to that specific term rather than retained at the root level."
ORYSJ	CKX2	IPR015345	GO:0009690	cytokinin metabolic process	MODIFY	yes	GO:0009823 cytokinin catabolic process	"""Cytokinin metabolic process"" is the parent term covering both biosynthesis and catabolism. OsCKX2 acts exclusively on the CATABOLIC side - it irreversibly degrades active cytokinins by oxidative side-chain cleavage [PMID:15976269] - so the more specific and accurate child term ""cytokinin catabolic process"" (GO:0009823) should be used. This is supported directly by the disruption phenotype (cytokinin ACCUMULATION when the gene is knocked down), which is diagnostic of a degradative enzyme."
ORYSJ	CKX2	IPR006094,IPR015345,IPR016164,IPR036318	GO:0050660	flavin adenine dinucleotide binding	ACCEPT	no		"Correct and well supported. The UniProt COFACTOR block lists FAD (ChEBI:57692), the protein belongs to the ""oxygen-dependent FAD-linked oxidoreductase"" family, and the entry annotates multiple FAD-binding residues plus a covalent 8-alpha-FAD histidine (His113) within the FAD-binding PCMH-type domain. FAD binding is intrinsic to the cytokinin dehydrogenase mechanism."
ORYSJ	CKX2	IPR016166	GO:0071949	FAD binding	ACCEPT	no		Correct, for the same reasons as the GO:0050660 annotation: OsCKX2 is an FAD-linked flavoenzyme with a defined FAD-binding PCMH-type domain and a covalently bound FAD cofactor (UniProt). Duplicate/overlapping FAD-binding terms with the same evidence are acceptable; the cofactor binding is a genuine, conserved feature of the CKX family.
ORYSJ	COQ5	IPR004033,IPR023576	GO:0008168	methyltransferase activity	MARK_AS_OVER_ANNOTATED	yes	GO:0008425 2-methoxy-6-polyprenyl-1,4-benzoquinol methyltransferase activity	"""Methyltransferase activity"" is a broad parent term. It is not wrong - COQ5 is a SAM-dependent methyltransferase - but it is uninformative now that the specific MF ""2-methoxy-6-polyprenyl-1,4-benzoquinol methyltransferase activity"" (GO:0008425) is annotated (IBA and IEA). The InterPro signatures that produced this term (UbiE/COQ5 family) actually map to the specific UbiE/COQ5 activity, so the more precise GO:0008425 better represents the same evidence (file:ORYSJ/COQ5/COQ5-deep-research-falcon.md). Retaining a generic ""methyltransferase activity"" alongside the specific term adds no information; it is an over-annotation relative to GO:0008425."
ORYSJ	CPS4	IPR001906,IPR036965,IPR050148	GO:0010333	terpene synthase activity	ACCEPT	no		"Correct and useful as a family-level molecular function. GO:0010333 is defined as ""Catalysis of the formation of cyclic terpenes through the cyclization of linear terpenes (e.g. ... geranylgeranyl-PP)"", which exactly matches OsCPS4's class II cyclization of GGPP. It is the direct parent grouping for the specific MF ""syn-copalyl diphosphate synthase activity"" (GO:0051498, also annotated). Retaining the family-level term alongside the specific term is acceptable; both are accurate."
ORYSJ	CPS4	IPR050148	GO:0016114	terpenoid biosynthetic process	MODIFY	yes	GO:0016102 diterpenoid biosynthetic process	"The biosynthetic direction is right, but the term can be made more specific. OsCPS4 cyclizes a C20 diterpenoid precursor (GGPP) into syn-CPP, the committed intermediate of rice syn-labdane diterpenoid biosynthesis [PMID:15255861, PMID:15341631]. ""Diterpenoid biosynthetic process"" (GO:0016102), a child of GO:0016114, is the precise term. Recommend modifying to GO:0016102 (this also consolidates with the MODIFY proposed for the GO:0006721 ARBA annotation)."
ORYSJ	CPS4	IPR001906,IPR036965	GO:0016829	lyase activity	MARK_AS_OVER_ANNOTATED	yes		"""Lyase activity"" is an uninformative high-level parent. The committed reaction is a proton- initiated bicyclization of GGPP to syn-CPP (EC 5.5.1.14), classified by the EC as an intramolecular lyase; the precise, specific molecular function ""syn-copalyl diphosphate synthase activity"" (GO:0051498) is already annotated with direct experimental (EXP) evidence [PMID:15255861, PMID:15341631] and the family grouping ""terpene synthase activity"" (GO:0010333) is also present. Once those informative MF terms are in place, the bare ""lyase activity"" parent adds no information. Marked as over-annotated; if any intermediate grouping were retained, the mechanistically accurate one would be ""intramolecular lyase activity"" (GO:0016872) rather than generic ""lyase activity""."
ORYSJ	EME1	IPR006166	GO:0003677	DNA binding	ACCEPT	no		"Correct. The ERCC4 domain has nucleic-acid-binding activity, and recombinant OsEME1 and OsEME1-C show major binding shifts on branched Y12 substrates in EMSA, with a measured substrate Kd of ~16 microM by microscale thermophoresis [PMID:40333587]. ""DNA binding"" is a generic term; the more informative activity is the structure- specific endonuclease MF (see the NEW GO:0008821 entry), but the DNA-binding IEA is not incorrect and can be accepted."
ORYSJ	EME1	IPR033310	GO:0006281	DNA repair	ACCEPT	no		"Core function, strongly supported by direct rice evidence. oseme1 mutants are hypersensitive to DNA-damaging agents (MMS, Zeocin), accumulate gamma-H2AX foci and show DNA-damage-induced cell-cycle arrest [PMID:40333587]. OsEME1 cleaves branched HR-repair intermediates in vitro. The term is appropriate, though the more specific ""double-strand break repair"" (GO:0006302, IBA, retained) and the proposed GO:0000724 better capture the HR-specific mechanism."
ORYSJ	EME1	IPR033310	GO:0048476	Holliday junction resolvase complex	ACCEPT	no		Correct and consistent with the IBA annotation to the same term and with direct evidence that OsEME1 interacts with OsMUS81 to form a structure-specific endonuclease complex [PMID:40333587]. Duplicate annotations with different evidence codes are acceptable; the IEA provides additional computational support for a well-established complex membership.
ORYSJ	GI	IPR026211	GO:2000028	regulation of photoperiodism, flowering	ACCEPT	no		"This is the core function of OsGI and is well supported by direct experimental evidence. Transgenic overexpression of OsGI caused late flowering under both SD and LD, increased expression of the rice CONSTANS orthologue (Hd1) and suppressed the rice FT orthologue (Hd3a), demonstrating that OsGI regulates the photoperiodic flowering pathway upstream of Hd1 (PMID:12700762). Review syntheses place OsGI upstream of Hd1 in the OsGI-Hd1-Hd3a module [file:ORYSJ/GI/GI-deep-research-falcon.md]. The InterPro2GO mapping gives the correct ""regulation of"" framing - OsGI regulates the photoperiodic flowering process rather than being a structural component of flowers - and is at an appropriate level of specificity. It directly captures the function UniProt describes (""control of the photoperiodic flowering ... Activates Hd1/CONSTANS gene""). This annotation is the correct replacement sense for the retired keyword-derived ""flower development"" SPKW term reviewed below."
ORYSJ	MADS3	IPR033896	GO:0000977	RNA polymerase II transcription regulatory region sequence-specific DNA binding	ACCEPT	no		Consistent with the IBA annotation and with the documented MADS-domain DNA-binding activity of OsMADS3. The InterPro-derived term is correct; it overlaps the more precise cis-regulatory-region term (GO:0000978) but is not wrong. Duplicate / closely related sequence-specific DNA-binding terms with different evidence codes are acceptable.
ORYSJ	MADS3	IPR002100,IPR036879	GO:0003677	DNA binding	ACCEPT	no		"Correct but generic. OsMADS3 is a DNA-binding MADS-box transcription factor; ""DNA binding"" is a true high-level parent of its sequence-specific cis-regulatory DNA binding (GO:0000978 / GO:0000977). It is uninformative compared with the specific sequence-specific terms but is not incorrect, so it can be accepted as supporting computational evidence."
ORYSJ	MADS3	IPR002487	GO:0003700	DNA-binding transcription factor activity	ACCEPT	no		Core, correct molecular function. OsMADS3 is the rice AGAMOUS ortholog, a MIKC-type MADS-box transcription factor that binds DNA sequence-specifically and regulates transcription of floral developmental targets. The InterPro-derived TF-activity term is appropriate.
ORYSJ	MADS3	IPR002487	GO:0006355	regulation of DNA-templated transcription	ACCEPT	no		"Correct but broad. OsMADS3 regulates transcription of its floral developmental targets (e.g. it binds and induces the MT-1-4b promoter). ""Regulation of DNA-templated transcription"" is a true high-level parent of the more specific ""regulation of transcription by RNA polymerase II"" (GO:0006357, IBA). It is not wrong and provides consistent computational support; the RNA-Pol-II-specific term is the more informative one."
ORYSJ	MADS3	IPR033896	GO:0045944	positive regulation of transcription by RNA polymerase II	ACCEPT	no		"Supported. OsMADS3 is annotated by UniProt with the keyword ""Activator"", and the literature reports that it binds the MT-1-4b promoter and strongly induces OsMT-I-4b, a direct positive transcriptional-regulation activity. MADS-box C-class factors can both activate and repress targets, but a positive-regulation activity is genuinely documented, so the IEA term is acceptable."
ORYSJ	MADS3	IPR002100,IPR036879	GO:0046983	protein dimerization activity	ACCEPT	no		Correct. The K-box domain (residues 87-178) mediates dimerization and higher-order complex formation, the structural basis of the floral-quartet model. OsMADS3 is reported to form complexes with SEP-like proteins (OsMADS1, OsMADS5, OsMADS24/8, OsMADS34, OsMADS45/7), and the K-box splice variation is interpreted as affecting protein-protein interaction capacity. Protein dimerization activity is a genuine, family-conserved molecular function.
ORYSJ	MET1A	IPR001025	GO:0003682	chromatin binding	ACCEPT	no		Supported by domain content. UniProt annotates two BAH domains (residues 742-874 and 910-1049) in MET1A, and the InterPro BAH-to-GO mapping assigns chromatin binding. BAH domains in DNMT1/MET1 read chromatin/nucleosome marks to target maintenance methylation to replicating heterochromatin, so chromatin binding is an appropriate, if generic, molecular-function annotation for this enzyme.
ORYSJ	MET1A	IPR001525	GO:0008168	methyltransferase activity	MARK_AS_OVER_ANNOTATED	yes		"""Methyltransferase activity"" is a broad grouping term. MET1A is a methyltransferase, so the term is not wrong, but it is uninformative once the specific child term DNA (cytosine-5-)- methyltransferase activity (GO:0003886, retained above) is present - the specific term drops both the substrate (DNA) and the position (C5 of cytosine). Retaining a bare ""methyltransferase activity"" alongside the specific MF adds no information. Mark as over-annotated; the specific MF is the one to keep."
ORYSJ	XA21	IPR000719,IPR008271	GO:0004672	protein kinase activity	ACCEPT	no		"Correct but generic. XA21 has a bona fide cytoplasmic protein kinase domain (residues 720-1019, PROSITE PS50011) and is autophosphorylated on Ser/Thr residues [UniProt Q2R2D5]. ""Protein kinase activity"" is the broad parent; the more specific ""protein serine/threonine kinase activity"" (GO:0004674) and the receptor-specific term (GO:0004675, proposed below) better capture the activity, but this parent IEA is not incorrect."
ORYSJ	XA21	IPR000719,IPR017441	GO:0005524	ATP binding	ACCEPT	no		Correct. The XA21 kinase domain contains a canonical ATP-binding motif (UniProt BINDING 726-734 and 748; PROSITE PS00107), required for autophosphorylation and transphosphorylation. Mutating the conserved ATP-binding lysine (K736E) abolishes XA21 kinase activity and its kinase-dependent interactions [PMID:24482436]. ATP binding is an integral part of the kinase MF.
PANPA	A0A2R9CAF4	IPR018045	GO:0008271	secondary active sulfate transmembrane transporter activity	ACCEPT	no		Sulfate transporter activity is a core function of SLC26A11, directly demonstrated by reconstitution studies with purified protein.
PANPA	A0A2R9CAF4	IPR001902	GO:0055085	transmembrane transport	KEEP_AS_NON_CORE	yes		Correct but too general; subsumed by the more specific sulfate and chloride transmembrane transport annotations.
PARTE	A0BFB4	IPR008271	GO:0004672	protein kinase activity	MARK_AS_OVER_ANNOTATED	yes		This is a parent term of GO:0004674 (protein serine/threonine kinase activity), which is already annotated with both IBA and IEA evidence. The more specific term is preferred; this redundant parent annotation adds no value.
PENEN	patI	IPR001128,IPR002401,IPR036396	GO:0005506	iron ion binding	ACCEPT	no		Correct - cytochrome P450 enzymes require iron ion binding through their heme cofactor. This is supported by UniProt annotation showing heme binding at residue 446 with iron as the central metal.
PENEN	patI	IPR001128,IPR002401,IPR036396	GO:0016705	oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen	ACCEPT	no		Correct and more specific than general oxidoreductase activity. This accurately describes the mechanism of cytochrome P450 monooxygenases, which incorporate one oxygen atom into the substrate while reducing the other to water.
PENEN	patI	IPR001128,IPR002401,IPR036396	GO:0020037	heme binding	ACCEPT	no		Correct - essential cofactor for cytochrome P450 function. UniProt shows heme binding at residue 446 with experimental evidence. Heme is required for the monooxygenase catalytic activity.
PHAVU	LBA	IPR001032,IPR012292,IPR019824	GO:0019825	oxygen binding	ACCEPT	no		Reversible O2 binding at the ferrous heme is the defining molecular activity of leghemoglobin and is directly consistent with the UniProt FUNCTION statement and the globin domain architecture. The InterPro-based assignment is at an appropriate level of specificity for a globin and is corroborated by the literature synthesis describing PvLba as an oxygen-binding heme globin.
PHAVU	LBA	IPR000971,IPR001032,IPR012292,IPR019824	GO:0020037	heme binding	ACCEPT	no		"Heme binding is essential to leghemoglobin function: O2 is bound at a pentacoordinated ferrous heme b, and UniProt annotates heme b binding residues (e.g. His-93 proximal, and contacts at 46 and 96) on the bean protein. The deep-research synthesis explicitly describes PvLba as a heme-binding globin. This is the more informative and specific molecular-function counterpart to the broad SPKW ""metal ion binding"" term and is the preferred replacement target for it."
PHYPA	MPK4a	IPR000719,IPR008271	GO:0004672	protein kinase activity	ACCEPT	no		"Correct but generic. MPK4a is a bona fide protein kinase - it has an intact kinase domain (residues 39-325), the proton-acceptor active site (Lys/Asp) and the ATP-binding site, and phosphorylates myelin basic protein in vitro [PMID:27268428]. ""Protein kinase activity"" is a true parent of the more specific and informative MAP kinase activity (GO:0004707) and protein serine/threonine kinase activity terms retained below; acceptable as a broad molecular-function parent."
PHYPA	MPK4a	IPR000719,IPR003527,IPR017441	GO:0005524	ATP binding	ACCEPT	no		"Correct. MPK4a is an ATP-dependent Ser/Thr kinase (EC 2.7.11.24) with an annotated ATP-binding site (residues 45-53 and 68 in the UniProt feature table) and uses ATP as the phosphate donor in kinase assays. ""ATP binding"" is a well-supported molecular-function annotation for any active protein kinase."
POLH7	AJ80_06654	IPR001287,IPR011707	GO:0005507	copper ion binding	ACCEPT	no		The UniProt record includes cupredoxin/multicopper oxidase family signatures and conserved type 1 copper-site features. These support copper binding even though no species-specific biochemical study was found. Falcon supports T1Cu/T2Cu architecture as the conserved CuNIR mechanism.
POPTR	ACCC1	IPR005479,IPR011761,IPR013815	GO:0005524	ATP binding	KEEP_AS_NON_CORE	yes		The catalytic activity consumes ATP (the biotin carboxylase ATP-grasp domain hydrolyzes ATP to drive biotin carboxylation), but biotin carboxylase activity captures the enzyme function more specifically. ATP binding is retained as a supporting, non-core molecular function.
POPTR	ACCC1	IPR004549	GO:0016874	ligase activity	MODIFY	yes	GO:0004075 biotin carboxylase activity	The reviewed entry specifies biotin carboxylase activity (EC 6.3.4.14), a precise ATP-dependent carboxylase reaction; falcon deep research likewise describes this subunit as the biotin carboxylase (BC) catalytic component performing the biotin-carboxylation half-reaction of ACCase. The generic 'ligase activity' parent should be replaced with GO:0004075.
POPTR	ACCC1	IPR011761	GO:0046872	metal ion binding	KEEP_AS_NON_CORE	yes		UniProt notes Mg(2+) or Mn(2+) cofactors, but the core function is biotin carboxylase activity.
POPTR	ACCC2	IPR005479,IPR011761,IPR013815	GO:0005524	ATP binding	KEEP_AS_NON_CORE	yes		The catalytic activity consumes ATP, but biotin carboxylase activity captures the enzyme function more specifically.
POPTR	ACCC2	IPR004549	GO:0016874	ligase activity	MODIFY	yes	GO:0004075 biotin carboxylase activity	The reviewed entry specifies biotin carboxylase activity, a precise ATP-dependent carboxylase reaction.
POPTR	ACCC2	IPR011761	GO:0046872	metal ion binding	KEEP_AS_NON_CORE	yes		UniProt notes Mg(2+) or Mn(2+) cofactors, but the core function is biotin carboxylase activity.
POPTR	ADLE	IPR034603	GO:0016855	racemase and epimerase activity, acting on amino acids and derivatives	ACCEPT	no		This term is more informative than the bare racemase/epimerase parent and accurately describes activity on amino-acid-derived substrates (dipeptides), matching the experimentally demonstrated dipeptide epimerase function.
POPTR	ALARS	IPR002318,IPR018162,IPR018163,IPR018164	GO:0000166	nucleotide binding	KEEP_AS_NON_CORE	yes		The enzyme binds ATP during the activation step; the generic nucleotide binding term is true but less informative than the ATP binding annotation also present, so it is retained as a non-core annotation.
POPTR	ALARS	IPR003156,IPR018165	GO:0003676	nucleic acid binding	KEEP_AS_NON_CORE	yes		The functionally meaningful binding is tRNA(Ala) binding; the broad nucleic acid binding parent is true but uninformative for this aminoacyl-tRNA synthetase, so it is retained as a non-core annotation.
POPTR	ALARS	IPR012947	GO:0004812	aminoacyl-tRNA ligase activity	KEEP_AS_NON_CORE	yes		The specific alanine-tRNA ligase activity (GO:0004813) better captures the curated catalytic activity than this family-level parent term, which is true but redundant and so is retained as a non-core annotation.
POPTR	ALARS	IPR002318,IPR018162	GO:0005737	cytoplasm	KEEP_AS_NON_CORE	yes		In GO the plastid and mitochondrion are part of the cytoplasm, so this broad term is technically correct but redundant with the specific organellar locations; it is retained as a non-core annotation rather than the principal localization.
POPTR	ALARS	IPR012947	GO:0043039	tRNA aminoacylation	KEEP_AS_NON_CORE	yes		The specific alanyl-tRNA aminoacylation term (GO:0006419) better captures the process than this broad parent, which is true but redundant and so is retained as a non-core annotation.
POPTR	CCOAOMT1	IPR002935	GO:0008171	O-methyltransferase activity	MODIFY	yes	GO:0042409 caffeoyl-CoA O-methyltransferase activity	Use the specific EC/Rhea-supported caffeoyl-CoA O-methyltransferase term. UniProt names the protein with the specific EC 2.1.1.104, and the falcon deep research confirms it is a SAM-dependent O-methyltransferase acting on hydroxycinnamoyl-CoA esters, so the generic O-methyltransferase term should be replaced with the specific activity.
POPTR	CCOAOMT2	IPR002935	GO:0008171	O-methyltransferase activity	MODIFY	yes	GO:0042409 caffeoyl-CoA O-methyltransferase activity	Use the specific EC/Rhea-supported caffeoyl-CoA O-methyltransferase term.
POPTR	CYN	IPR010982	GO:0003677	DNA binding	MARK_AS_OVER_ANNOTATED	yes		The UniProt function and catalytic activity support cyanate hydratase activity only. This IEA row derives from the lambda-repressor-like DNA-binding fold (IPR010982) that the cyanase N-terminal domain shares structurally; the falcon deep-research synthesis of plant cyanases reports the enzyme as a cyanate-detoxifying lyase and provides no evidence for DNA binding as a function.
POPTR	DRE2	IPR007785	GO:0051536	iron-sulfur cluster binding	KEEP_AS_NON_CORE	yes		The protein binds defined [2Fe-2S] and [4Fe-4S] clusters; the generic parent term is true but less informative than the specific cluster-binding annotations also present, so it is retained as a non-core annotation.
POPTR	EIN2.1	IPR017187	GO:0009873	ethylene-activated signaling pathway	ACCEPT	no		The reviewed entry describes EIN2 as a central factor in ethylene-regulated signaling. Falcon deep research positions EIN2 as the central transducer of the ethylene pathway, acting downstream of receptors and CTR1 and upstream of EIN3/EIL transcription factors, consistent with the conserved EIN2 mechanism.
POPTR	EIN2.1	IPR001046	GO:0016020	membrane	MODIFY	yes	GO:0005789 endoplasmic reticulum membrane	Use endoplasmic reticulum membrane for the membrane-bound EIN2 protein.
POPTR	EIN2.1	IPR001046	GO:0030001	metal ion transport	MARK_AS_OVER_ANNOTATED	yes		EIN2 has an NRAMP-like N-terminal domain, but the reviewed functional annotation is ethylene signaling, not demonstrated metal transport. Falcon deep research found no transport assay or substrate-specificity data for Populus EIN2.1, treating any transporter claim as database-derived inference pending validation.
POPTR	EIN2.1	IPR001046	GO:0046873	metal ion transmembrane transporter activity	MARK_AS_OVER_ANNOTATED	yes		EIN2 has an NRAMP-like N-terminal domain, but the reviewed functional annotation is ethylene signaling, not demonstrated metal transport. Falcon deep research found no transport assay or substrate-specificity data for Populus EIN2.1, treating any transporter claim as database-derived inference pending validation.
POPTR	EIN2.2	IPR017187	GO:0009873	ethylene-activated signaling pathway	ACCEPT	no		The reviewed entry describes EIN2 as a central factor in ethylene-regulated signaling.
POPTR	EIN2.2	IPR001046	GO:0016020	membrane	MODIFY	yes	GO:0005789 endoplasmic reticulum membrane	Use endoplasmic reticulum membrane for the membrane-bound EIN2 protein.
POPTR	EIN2.2	IPR001046	GO:0030001	metal ion transport	MARK_AS_OVER_ANNOTATED	yes		EIN2 has an NRAMP-like N-terminal domain, but the reviewed functional annotation is ethylene signaling, not demonstrated metal transport.
POPTR	EIN2.2	IPR001046	GO:0046873	metal ion transmembrane transporter activity	MARK_AS_OVER_ANNOTATED	yes		EIN2 has an NRAMP-like N-terminal domain, but the reviewed functional annotation is ethylene signaling, not demonstrated metal transport.
POPTR	FL	IPR002910,IPR035209	GO:0003677	DNA binding	MODIFY	yes	GO:0003700 DNA-binding transcription factor activity	FL/PTLF is a FLO/LFY-family transcription factor with a characteristic LEAFY DNA-binding fold. The generic GO:0003677 (DNA binding) should be refined to GO:0003700 (DNA-binding transcription factor activity), which captures the sequence-specific, cis-regulatory DNA-binding mechanism of LEAFY-class transcription factors. Falcon deep research recommends annotating O04064 first-and-foremost by its DNA-binding fold/class and TF mechanism rather than a generic label.
POPTR	FL	IPR002910	GO:0006355	regulation of DNA-templated transcription	ACCEPT	no		FL/PTLF is a LEAFY-family nuclear transcription factor that regulates floral developmental gene-expression programs. Falcon deep research describes the FLO/LFY family as plant-specific developmental transcription factors that regulate the transition to flowering.
POPTR	GATC	IPR003837,IPR036113	GO:0006450	regulation of translational fidelity	KEEP_AS_NON_CORE	yes		Retain as non-core while using glutaminyl-tRNAGln biosynthesis via transamidation as the direct process; by correcting ND-GluRS misacylation, GatCAB does contribute to faithful organellar translation.
POPTR	LIP1	IPR006638,IPR007197	GO:0003824	catalytic activity	MODIFY	yes	GO:0016992 lipoate synthase activity	Use the specific lipoate synthase activity term.
POPTR	LIP1	IPR006638,IPR007197	GO:0051536	iron-sulfur cluster binding	MODIFY	yes	GO:0051539 4 iron, 4 sulfur cluster binding	The reviewed entry specifies two 4Fe-4S clusters per subunit.
POPTR	LIP1P-1	IPR006638,IPR007197	GO:0003824	catalytic activity	MODIFY	yes	GO:0016992 lipoate synthase activity	Use the specific lipoate synthase activity term.
POPTR	LIP1P-1	IPR006638,IPR007197	GO:0051536	iron-sulfur cluster binding	MODIFY	yes	GO:0051539 4 iron, 4 sulfur cluster binding	The UniProt cofactor annotation specifies two 4Fe-4S clusters.
POPTR	LIP1P-2	IPR006638,IPR007197	GO:0003824	catalytic activity	MODIFY	yes	GO:0016992 lipoate synthase activity	Use the specific lipoate synthase activity term.
POPTR	LIP1P-2	IPR006638,IPR007197	GO:0051536	iron-sulfur cluster binding	MODIFY	yes	GO:0051539 4 iron, 4 sulfur cluster binding	The UniProt cofactor annotation specifies two 4Fe-4S clusters.
POPTR	MAOX	IPR001891,IPR012301,IPR037062	GO:0004470	malic enzyme activity	MODIFY	yes	GO:0004473 malate dehydrogenase (decarboxylating) (NADP+) activity	UniProt specifies NADP-dependent malate dehydrogenase (decarboxylating) activity with EC 1.1.1.40, and deep-research literature defines this plant NADP-ME as an oxidative decarboxylase catalyzing L-malate + NADP+ to pyruvate, CO2, and NADPH; the more specific GO:0004473 captures the NADP cofactor and decarboxylating direction.
POPTR	MAOX	IPR001891,IPR012301,IPR037062	GO:0016616	oxidoreductase activity, acting on the CH-OH group of donors, NAD or NADP as acceptor	MODIFY	yes	GO:0004473 malate dehydrogenase (decarboxylating) (NADP+) activity	UniProt provides the specific malate dehydrogenase (decarboxylating) NADP-dependent reaction, and deep-research literature confirms NADP+ (not NAD+) as the electron acceptor for this enzyme, so the specific GO:0004473 better captures the cofactor and reaction than the broad NAD-or-NADP oxidoreductase grouping term.
POPTR	MAOX	IPR012302	GO:0051287	NAD binding	MODIFY	yes	GO:0050661 NADP binding	UniProt feature annotations include NAD(+) binding positions and NAD(P)-binding domains, but the reviewed protein name, keyword, and primary malic enzyme reaction specify NADP(+); this MODIFY therefore targets the primary catalytic cofactor rather than denying structural NAD binding.
POPTR	METK1	IPR002133	GO:0005524	ATP binding	KEEP_AS_NON_CORE	yes		Retain as a co-substrate binding feature, not as the core function.
POPTR	METK2	IPR002133	GO:0005524	ATP binding	KEEP_AS_NON_CORE	yes		Retain as a co-substrate binding feature supporting catalysis, not as the core function (methionine adenosyltransferase activity is the core MF).
POPTR	METK3	IPR002133	GO:0005524	ATP binding	KEEP_AS_NON_CORE	yes		Retain as a co-substrate binding feature, not as the core function.
POPTR	METK4	IPR002133	GO:0005524	ATP binding	KEEP_AS_NON_CORE	yes		Retain as a co-substrate binding feature, not as the core function.
POPTR	METK5	IPR002133	GO:0005524	ATP binding	KEEP_AS_NON_CORE	yes		Retain as a co-substrate binding feature, not as the core function.
POPTR	MTNB	IPR017714,IPR027514	GO:0005737	cytoplasm	ACCEPT	no		Consistent with the cytoplasmic methionine salvage cycle and the IBA cytoplasm annotation.
POPTR	MTNB	IPR017714,IPR027514	GO:0046872	metal ion binding	KEEP_AS_NON_CORE	yes		The enzyme binds specific metals (Zn2+ and Mg2+) already captured by GO:0008270 and GO:0000287; the generic metal ion binding parent is true but redundant, so it is kept as a non-core annotation.
POPTR	NRAMP1	IPR001046	GO:0030001	metal ion transport	ACCEPT	no		The function is annotated at the family level as a probable divalent metal transporter; the general metal ion transport process matches the available evidence without overstating substrate specificity.
POPTR	NRAMP1	IPR001046	GO:0046873	metal ion transmembrane transporter activity	ACCEPT	no		The probable divalent metal transporter function and NRAMP family membership support this general transmembrane transporter activity without claiming a specific substrate not yet demonstrated for this paralog.
POPTR	NRAMP2	IPR001046	GO:0030001	metal ion transport	ACCEPT	no		The reviewed entry and family-level evidence support a probable divalent metal transporter role without direct cation-specific assays for this paralog, so the broad transport term is appropriate.
POPTR	NRAMP2	IPR001046	GO:0046873	metal ion transmembrane transporter activity	ACCEPT	no		The term matches the family-level transporter assignment without over-specifying the cation; a manganese-specific MF would over-claim substrate specificity that is not directly shown for B9GNS0.
POPTR	NRAMP3.1	IPR001046	GO:0016020	membrane	MODIFY	yes	GO:0032588 trans-Golgi network membrane	The annotation should use the specific membrane compartment rather than the generic membrane parent.
POPTR	NRAMP3.1	IPR001046	GO:0030001	metal ion transport	MODIFY	yes	GO:0034755 iron ion transmembrane transport; GO:0071421 manganese ion transmembrane transport	Specific iron and manganese transmembrane transport terms better capture the experimentally supported activity.
POPTR	NRAMP3.1	IPR001046	GO:0046873	metal ion transmembrane transporter activity	MODIFY	yes	GO:0005384 manganese ion transmembrane transporter activity; GO:0005381 iron ion transmembrane transporter activity	Use the specific cation transporter activities supported by yeast complementation and UniProt curation.
POPTR	NRAMP3.2	IPR001046	GO:0016020	membrane	MODIFY	yes	GO:0009705 plant-type vacuole membrane	The annotation should use the specific membrane compartment rather than the generic membrane parent.
POPTR	NRAMP3.2	IPR001046	GO:0030001	metal ion transport	MODIFY	yes	GO:0034755 iron ion transmembrane transport; GO:0071421 manganese ion transmembrane transport	Specific iron and manganese transmembrane transport terms better capture the experimentally supported activity.
POPTR	NRAMP3.2	IPR001046	GO:0046873	metal ion transmembrane transporter activity	MODIFY	yes	GO:0005384 manganese ion transmembrane transporter activity; GO:0005381 iron ion transmembrane transporter activity	Use the specific cation transporter activities supported by yeast complementation and UniProt curation.
POPTR	NRAMP6.1	IPR001046	GO:0030001	metal ion transport	ACCEPT	no		The reviewed entry supports a probable divalent metal transporter role without direct cation-specific assays for this paralog.
POPTR	NRAMP6.1	IPR001046	GO:0046873	metal ion transmembrane transporter activity	ACCEPT	no		The term matches the family-level transporter assignment without over-specifying the cation.
POPTR	NRAMP6.2	IPR001046	GO:0030001	metal ion transport	ACCEPT	no		The reviewed entry supports a probable divalent metal transporter role without direct cation-specific assays for this paralog.
POPTR	NRAMP6.2	IPR001046	GO:0046873	metal ion transmembrane transporter activity	ACCEPT	no		The term matches the family-level transporter assignment without over-specifying the cation.
POPTR	NRAMP7.1	IPR001046	GO:0030001	metal ion transport	ACCEPT	no		The reviewed entry supports a probable divalent metal transporter role without direct cation-specific assays.
POPTR	NRAMP7.1	IPR001046	GO:0046873	metal ion transmembrane transporter activity	ACCEPT	no		The term matches the family-level transporter assignment without over-specifying the cation.
POPTR	NRAMP7.2	IPR001046	GO:0030001	metal ion transport	ACCEPT	no		The reviewed entry supports a probable divalent metal transporter role without direct cation-specific assays.
POPTR	NRAMP7.2	IPR001046	GO:0046873	metal ion transmembrane transporter activity	ACCEPT	no		The term matches the family-level transporter assignment without over-specifying the cation.
POPTR	PAL	IPR008948	GO:0003824	catalytic activity	MODIFY	yes	GO:0045548 phenylalanine ammonia-lyase activity	Replace the root catalytic activity term with the specific phenylalanine ammonia-lyase activity term, which captures the actual reaction (L-phenylalanine to trans-cinnamate + NH4+).
POPTR	PAL	IPR005922	GO:0006559	L-phenylalanine catabolic process	ACCEPT	no		PAL deaminates L-phenylalanine to trans-cinnamate and ammonium, which is consumption (catabolism) of L-phenylalanine. Supported by the UniProt reaction and the falcon synthesis.
POPTR	PAL	IPR005922,IPR022313	GO:0016841	ammonia-lyase activity	MODIFY	yes	GO:0045548 phenylalanine ammonia-lyase activity	Replace the grouping term with the substrate-specific phenylalanine ammonia-lyase activity term, consistent with the UniProt reaction and the falcon entry-reaction description.
POPTR	PRX2	IPR037944	GO:0008379	thioredoxin peroxidase activity	KEEP_AS_NON_CORE	yes		UniProt and the biochemical literature show this peroxiredoxin uses either glutaredoxin or thioredoxin as a proton donor and preferentially uses glutaredoxin; the more general peroxiredoxin activity term better represents the core function, while thioredoxin peroxidase activity remains a correct supporting molecular function.
POPTR	PRX2	IPR013740	GO:0016491	oxidoreductase activity	KEEP_AS_NON_CORE	yes		The specific peroxiredoxin activity and thioredoxin peroxidase activity terms already capture the redox catalysis; the generic oxidoreductase parent is true but redundant, so it is retained as a non-core annotation rather than the principal function.
POPTR	PRX2	IPR037944	GO:0034599	cellular response to oxidative stress	ACCEPT	no		UniProt states the protein plays a role in cell protection against oxidative stress by detoxifying peroxides, which is exactly a cellular response to oxidative stress.
POPTR	PURA	IPR001114	GO:0000166	nucleotide binding	KEEP_AS_NON_CORE	yes		Retain as a broad substrate-binding feature, not the core molecular function.
POPTR	PURA	IPR001114	GO:0006164	purine nucleotide biosynthetic process	MODIFY	yes	GO:0044208 'de novo' AMP biosynthetic process	The reviewed pathway is specifically de novo AMP biosynthesis from IMP.
POPTR	RBL901	IPR028309	GO:0006357	regulation of transcription by RNA polymerase II	ACCEPT	no		UniProt states that RBL901 recruits a histone deacetylase to control gene transcription.
POPTR	RBL901	IPR002719,IPR002720,IPR028309	GO:0051726	regulation of cell cycle	ACCEPT	no		The reviewed entry describes negative regulation of cell proliferation/mitotic entry.
POPTR	TIC214	IPR008896	GO:0016020	membrane	KEEP_AS_NON_CORE	yes		The specific and supported location is the chloroplast inner envelope membrane (GO:0009706); the generic membrane parent is true but redundant with it, so it is kept as a non-core annotation.
POPTR	WIN6	IPR000726,IPR016283	GO:0004568	chitinase activity	MODIFY	yes	GO:0008843 endochitinase activity	The catalytic activity is random endo-hydrolysis of chitin, which is captured precisely by endochitinase activity rather than the broader chitinase parent.
POPTR	WIN6	IPR016283	GO:0005975	carbohydrate metabolic process	KEEP_AS_NON_CORE	yes		The more specific chitin catabolic process and cell wall macromolecule catabolic process terms already capture the biological role; the generic carbohydrate metabolism parent is true but redundant, so it is retained as a non-core annotation.
POPTR	WIN6	IPR000726	GO:0006032	chitin catabolic process	ACCEPT	no		The enzyme hydrolyzes chitin, so chitin catabolism is the immediate process it participates in.
POPTR	WIN6	IPR000726	GO:0016998	cell wall macromolecule catabolic process	ACCEPT	no		Hydrolysis of chitin, a fungal cell wall polysaccharide, is a cell wall macromolecule catabolic process consistent with the antifungal role.
POPTR	WIN6.2B	IPR000726,IPR016283	GO:0004568	chitinase activity	MODIFY	yes	GO:0008843 endochitinase activity	The catalytic activity is random endo-hydrolysis of chitin, captured precisely by endochitinase activity rather than the broader chitinase parent.
POPTR	WIN6.2B	IPR016283	GO:0005975	carbohydrate metabolic process	KEEP_AS_NON_CORE	yes		The more specific chitin catabolic process and cell wall macromolecule catabolic process terms already capture the role; the generic carbohydrate metabolism parent is true but redundant, so it is retained as a non-core annotation.
POPTR	WIN6.2B	IPR000726	GO:0006032	chitin catabolic process	ACCEPT	no		The enzyme hydrolyzes chitin, so chitin catabolism is the immediate process it participates in.
POPTR	WIN6.2B	IPR001002,IPR018371,IPR036861	GO:0008061	chitin binding	KEEP_AS_NON_CORE	yes		The protein has a dedicated chitin-binding type-1 domain, so chitin binding is well supported, but it is auxiliary to the catalytic endochitinase activity.
POPTR	WIN6.2B	IPR000726	GO:0016998	cell wall macromolecule catabolic process	ACCEPT	no		Hydrolysis of chitin, a fungal cell wall polysaccharide, is a cell wall macromolecule catabolic process consistent with the antifungal role.
POPTR	WIN6.2C	IPR000726	GO:0004568	chitinase activity	MODIFY	yes	GO:0008843 endochitinase activity	Correct but not specific enough. The enzyme is specifically an endochitinase.
POPTR	WIN6.2C	IPR000726	GO:0016998	cell wall macromolecule catabolic process	KEEP_AS_NON_CORE	yes		Correct broader process annotation; chitin is a cell wall macromolecule in fungi.
POPTR	WIN8	IPR000726,IPR016283	GO:0004568	chitinase activity	MODIFY	yes	GO:0008843 endochitinase activity	Use endochitinase activity for the random endo-hydrolysis reaction.
POPTR	WIN8	IPR016283	GO:0005975	carbohydrate metabolic process	MODIFY	yes	GO:0006032 chitin catabolic process	Replace with the specific chitin catabolic process term already supported by the enzyme reaction.
POPTR	WIN8	IPR000726	GO:0006032	chitin catabolic process	ACCEPT	no		The enzyme hydrolyzes chitin and chitodextrins.
POPTR	WIN8	IPR001002,IPR018371,IPR036861	GO:0008061	chitin binding	ACCEPT	no		UniProt and GO annotations support chitin binding for this plant chitinase.
POPTR	WIN8	IPR000726	GO:0016998	cell wall macromolecule catabolic process	KEEP_AS_NON_CORE	yes		Retain as non-core; chitin catabolic process and endochitinase activity are more informative.
POPTR	XGOAT1	IPR029962	GO:0016413	O-acetyltransferase activity	ACCEPT	no		The paper and UniProt entry describe transfer of acetyl groups onto xyloglucan oligomers.
POPTR	XGOAT1	IPR026057	GO:0016740	transferase activity	MODIFY	yes	GO:0016413 O-acetyltransferase activity	Use O-acetyltransferase activity; no current GO term specifically names xyloglucan O-acetyltransferase activity.
POPTR	XGOAT2	IPR029962	GO:0016413	O-acetyltransferase activity	ACCEPT	no		The paper and UniProt entry describe transfer of acetyl groups onto xyloglucan oligomers.
POPTR	XGOAT2	IPR026057	GO:0016740	transferase activity	MODIFY	yes	GO:0016413 O-acetyltransferase activity	Use O-acetyltransferase activity; no current GO term specifically names xyloglucan O-acetyltransferase activity.
POPTR	XGOAT3	IPR029962	GO:0016413	O-acetyltransferase activity	ACCEPT	no		The paper and UniProt entry describe transfer of acetyl groups onto xyloglucan oligomers.
POPTR	XGOAT3	IPR026057	GO:0016740	transferase activity	MODIFY	yes	GO:0016413 O-acetyltransferase activity	Use O-acetyltransferase activity; no current GO term specifically names xyloglucan O-acetyltransferase activity.
POPTR	XGOAT4	IPR029962	GO:0016413	O-acetyltransferase activity	ACCEPT	no		The paper and UniProt entry describe transfer of acetyl groups onto xyloglucan oligomers.
POPTR	XGOAT4	IPR026057	GO:0016740	transferase activity	MODIFY	yes	GO:0016413 O-acetyltransferase activity	Use O-acetyltransferase activity; no current GO term specifically names xyloglucan O-acetyltransferase activity.
POPTR	accD	IPR000438	GO:0003989	acetyl-CoA carboxylase activity	MODIFY	yes	GO:0003989 acetyl-CoA carboxylase activity	AccD is the plastid-coded beta carboxyltransferase subunit of the ACCase complex rather than the entire enzyme alone; the qualifier change is the modification.
POPTR	accD	IPR000438	GO:0006633	fatty acid biosynthetic process	ACCEPT	no		Malonyl-CoA produced by ACCase is the committed precursor for fatty acid synthesis.
POPTR	accD	IPR000438	GO:0009317	acetyl-CoA carboxylase complex	ACCEPT	no		The protein is explicitly described as an ACC complex component.
POPTR	atpA	IPR033732	GO:0032559	adenyl ribonucleotide binding	MODIFY	yes	GO:0005524 ATP binding; GO:0043531 ADP binding	Use the specific nucleotide-binding annotations.
POPTR	atpA	IPR005294	GO:0045259	proton-transporting ATP synthase complex	ACCEPT	no		The chloroplast ATP synthase F1 sector contains alpha subunits.
POPTR	atpA	IPR004100,IPR036121	GO:0046034	ATP metabolic process	KEEP_AS_NON_CORE	yes		Keep as non-core; the specific process is ATP synthesis driven by the proton motive force.
POPTR	atpA	IPR004100,IPR036121	GO:1902600	proton transmembrane transport	KEEP_AS_NON_CORE	yes		The alpha subunit contributes to the rotary ATP synthase complex rather than forming the proton channel alone.
POPTR	atpB	IPR005722	GO:0045259	proton-transporting ATP synthase complex	ACCEPT	no		The beta subunit is one of the CF1 catalytic core subunits of F-type ATP synthase.
POPTR	atpB	IPR004100,IPR036121	GO:0046034	ATP metabolic process	KEEP_AS_NON_CORE	yes		Retain as non-core; GO:0015986 captures the specific process.
POPTR	atpB	IPR004100,IPR036121	GO:1902600	proton transmembrane transport	KEEP_AS_NON_CORE	yes		The beta subunit is in the CF1 catalytic core; ATP synthesis is coupled to proton movement through CF0.
POPTR	atpF	IPR002146	GO:0015078	proton transmembrane transporter activity	MODIFY	yes	GO:0015078 proton transmembrane transporter activity	AtpF is a F0-channel/peripheral-stalk component of proton-transporting ATP synthase rather than an independent proton transporter, so the source enables qualifier should be changed to contributes_to.
POPTR	atpF	IPR002146	GO:0045259	proton-transporting ATP synthase complex	ACCEPT	no		UniProt identifies subunit b as one of the main F0 components linking F1 and F0.
POPTR	atpH	IPR000454,IPR002379,IPR005953	GO:0015078	proton transmembrane transporter activity	ACCEPT	no		Subunit c forms the rotor ring of the F0 proton channel, so contributes_to is the best relationship.
POPTR	atpH	IPR000454,IPR005953	GO:0015986	proton motive force-driven ATP synthesis	ACCEPT	no		The reviewed entry describes ATP production from ADP using a membrane proton gradient.
POPTR	atpH	IPR002379	GO:0033177	proton-transporting two-sector ATPase complex, proton-transporting domain	ACCEPT	no		Subunit c is a membrane proton-channel component of F0.
POPTR	atpH	IPR000454,IPR005953	GO:0045259	proton-transporting ATP synthase complex	ACCEPT	no		The F0 c-ring is a structural component of the thylakoid ATP synthase.
POPTR	atpH	IPR002379	GO:1902600	proton transmembrane transport	ACCEPT	no		UniProt states that subunit c has a direct role in translocation across the membrane.
POPTR	atpI	IPR000568,IPR045082	GO:0015078	proton transmembrane transporter activity	ACCEPT	no		UniProt states that atpI is a key proton-channel component with a direct role in proton translocation.
POPTR	atpI	IPR000568,IPR045082	GO:0045259	proton-transporting ATP synthase complex	ACCEPT	no		UniProt identifies subunit a as one of the CF0 membrane proton-channel components.
POPTR	ccsA	IPR002541,IPR045062	GO:0020037	heme binding	ACCEPT	no		CcsA functions in heme attachment during c-type cytochrome biogenesis, and InterPro supplies the heme binding annotation.
POPTR	cemA	IPR004282	GO:0016020	membrane	MODIFY	yes	GO:0009706 chloroplast inner membrane	Use the specific chloroplast inner membrane location.
POPTR	clpP	IPR001907	GO:0004176	ATP-dependent peptidase activity	ACCEPT	no		UniProt describes peptide cleavage requiring ATP hydrolysis, consistent with ClpP acting in the ATP-dependent Clp protease complex.
POPTR	matK	IPR002866,IPR024937	GO:0006397	mRNA processing	ACCEPT	no		UniProt states that MatK assists splicing of chloroplast group II introns.
POPTR	ndhA	IPR001694,IPR018086	GO:0016020	membrane	MODIFY	yes	GO:0009535 chloroplast thylakoid membrane	Use the specific thylakoid membrane location supported by UniProt.
POPTR	ndhB1	IPR010096	GO:0008137	NADH dehydrogenase (ubiquinone) activity	MODIFY	yes	GO:0016655 oxidoreductase activity, acting on NAD(P)H, quinone or similar compound as acceptor	The reviewed chloroplast reaction uses plastoquinone and NAD(P)H; the broader quinone-acceptor oxidoreductase term is safer.
POPTR	ndhB1	IPR010096	GO:0042773	ATP synthesis coupled electron transport	KEEP_AS_NON_CORE	yes		Keep as non-core; the direct process is NDH electron transfer coupled to proton translocation.
POPTR	ndhB2	IPR010096	GO:0008137	NADH dehydrogenase (ubiquinone) activity	MODIFY	yes	GO:0016655 oxidoreductase activity, acting on NAD(P)H, quinone or similar compound as acceptor	The reviewed chloroplast reaction uses plastoquinone and NAD(P)H; the broader quinone-acceptor oxidoreductase term is safer.
POPTR	ndhB2	IPR010096	GO:0042773	ATP synthesis coupled electron transport	KEEP_AS_NON_CORE	yes		Keep as non-core; the direct process is NDH electron transfer coupled to proton translocation.
POPTR	ndhC	IPR000440	GO:0008137	NADH dehydrogenase (ubiquinone) activity	MODIFY	yes	GO:0016655 oxidoreductase activity, acting on NAD(P)H, quinone or similar compound as acceptor	The reviewed chloroplast reaction uses plastoquinone and NAD(P)H; the broader quinone-acceptor oxidoreductase term is safer.
POPTR	ndhC	IPR023043	GO:0016651	oxidoreductase activity, acting on NAD(P)H	MODIFY	yes	GO:0016655 oxidoreductase activity, acting on NAD(P)H, quinone or similar compound as acceptor	Use the more specific NAD(P)H/quinone oxidoreductase activity term already supported by UniRule.
POPTR	ndhD	IPR003918,IPR010227	GO:0008137	NADH dehydrogenase (ubiquinone) activity	MODIFY	yes	GO:0016655 oxidoreductase activity, acting on NAD(P)H, quinone or similar compound as acceptor	The chloroplast reaction uses plastoquinone and NAD(P)H, so the broader quinone-acceptor oxidoreductase term is safer.
POPTR	ndhD	IPR003918,IPR010227	GO:0042773	ATP synthesis coupled electron transport	KEEP_AS_NON_CORE	yes		Keep as non-core; the direct process is electron transport coupled proton transport.
POPTR	ndhE	IPR001133	GO:0016651	oxidoreductase activity, acting on NAD(P)H	MODIFY	yes	GO:0016655 oxidoreductase activity, acting on NAD(P)H, quinone or similar compound as acceptor	The reviewed reaction transfers electrons from NADH/NADPH to plastoquinone.
POPTR	ndhE	IPR001133	GO:0042773	ATP synthesis coupled electron transport	KEEP_AS_NON_CORE	yes		Keep as non-core; the direct process is electron transport coupled proton transport.
POPTR	ndhF	IPR003945,IPR018393	GO:0008137	NADH dehydrogenase (ubiquinone) activity	MODIFY	yes	GO:0016655 oxidoreductase activity, acting on NAD(P)H, quinone or similar compound as acceptor	The reviewed chloroplast reaction uses plastoquinone and NAD(P)H; the broader quinone-acceptor oxidoreductase term is safer.
POPTR	ndhF	IPR003945,IPR018393	GO:0042773	ATP synthesis coupled electron transport	KEEP_AS_NON_CORE	yes		Keep as non-core; the direct process is electron transport coupled proton transport.
POPTR	ndhG	IPR001457	GO:0008137	NADH dehydrogenase (ubiquinone) activity	MODIFY	yes	GO:0016655 oxidoreductase activity, acting on NAD(P)H, quinone or similar compound as acceptor	The chloroplast reaction uses plastoquinone and NAD(P)H, so the broader quinone-acceptor oxidoreductase term is safer.
POPTR	ndhH	IPR001135,IPR014029,IPR022885	GO:0016651	oxidoreductase activity, acting on NAD(P)H	MODIFY	yes	GO:0016655 oxidoreductase activity, acting on NAD(P)H, quinone or similar compound as acceptor	The reviewed chloroplast NDH reaction uses plastoquinone/quinone as the electron acceptor.
POPTR	ndhH	IPR001135	GO:0048038	quinone binding	KEEP_AS_NON_CORE	yes		Retain as a substrate-binding feature; the core function is contribution to NAD(P)H-quinone oxidoreductase activity.
POPTR	ndhH	IPR001135	GO:0051287	NAD binding	KEEP_AS_NON_CORE	yes		Retain as a nucleotide/cofactor-binding feature rather than the core function of the subunit.
POPTR	ndhI	IPR004497	GO:0008137	NADH dehydrogenase (ubiquinone) activity	MODIFY	yes	GO:0016655 oxidoreductase activity, acting on NAD(P)H, quinone or similar compound as acceptor	The chloroplast reaction uses plastoquinone and NAD(P)H, so the broader quinone-acceptor oxidoreductase term is safer.
POPTR	ndhI	IPR010226	GO:0016020	membrane	MODIFY	yes	GO:0009535 chloroplast thylakoid membrane	Use the specific thylakoid membrane location supported by UniProt.
POPTR	ndhI	IPR010226	GO:0016651	oxidoreductase activity, acting on NAD(P)H	MODIFY	yes	GO:0016655 oxidoreductase activity, acting on NAD(P)H, quinone or similar compound as acceptor	The reviewed reaction transfers electrons from NADH/NADPH to plastoquinone.
POPTR	ndhI	IPR010226	GO:0051539	4 iron, 4 sulfur cluster binding	ACCEPT	no		The reviewed entry states that the subunit binds two 4Fe-4S clusters.
POPTR	ndhJ	IPR001268	GO:0008137	NADH dehydrogenase (ubiquinone) activity	MODIFY	yes	GO:0016655 oxidoreductase activity, acting on NAD(P)H, quinone or similar compound as acceptor	The chloroplast reaction uses plastoquinone and NAD(P)H, so the broader quinone-acceptor oxidoreductase term is safer.
POPTR	ndhJ	IPR010218,IPR020396	GO:0016651	oxidoreductase activity, acting on NAD(P)H	MODIFY	yes	GO:0016655 oxidoreductase activity, acting on NAD(P)H, quinone or similar compound as acceptor	The reviewed reaction transfers electrons from NADH/NADPH to plastoquinone.
POPTR	ndhK	IPR006138	GO:0008137	NADH dehydrogenase (ubiquinone) activity	MODIFY	yes	GO:0016655 oxidoreductase activity, acting on NAD(P)H, quinone or similar compound as acceptor	The UniProt-curated reaction uses plastoquinone and NAD(P)H, so the broader quinone-acceptor oxidoreductase term is safer.
POPTR	ndhK	IPR006138	GO:0048038	quinone binding	ACCEPT	no		The catalytic reaction uses plastoquinone/plastoquinol.
POPTR	ndhK	IPR006137	GO:0051536	iron-sulfur cluster binding	MODIFY	yes	GO:0051539 4 iron, 4 sulfur cluster binding	The UniProt cofactor annotation specifies a single 4Fe-4S cluster.
POPTR	ndhK	IPR006138	GO:0051539	4 iron, 4 sulfur cluster binding	ACCEPT	no		This is a real cofactor-binding role for the ndhK subunit.
POPTR	petA	IPR002325	GO:0005506	iron ion binding	KEEP_AS_NON_CORE	yes		The more informative cofactor term is heme binding, and the core molecular role is electron transfer.
POPTR	petA	IPR002325	GO:0020037	heme binding	ACCEPT	no		The reviewed entry states that cytochrome f covalently binds one heme group.
POPTR	petA	IPR002325	GO:0042651	thylakoid membrane	MODIFY	yes	GO:0009535 chloroplast thylakoid membrane	Use the specific chloroplast thylakoid membrane location.
POPTR	petG	IPR003683,IPR036099	GO:0009512	cytochrome b6f complex	ACCEPT	no		The reviewed entry explicitly identifies this protein as a cytochrome b6-f complex subunit.
POPTR	petL	IPR007802	GO:0009512	cytochrome b6f complex	ACCEPT	no		The reviewed entry explicitly lists PetL among the small subunits of the cytochrome b6-f complex.
POPTR	petN	IPR005497,IPR036143	GO:0009512	cytochrome b6f complex	ACCEPT	no		The reviewed entry explicitly identifies this protein as a cytochrome b6-f complex subunit.
POPTR	psaA	IPR001280	GO:0009579	thylakoid	MODIFY	yes	GO:0009535 chloroplast thylakoid membrane	The reviewed protein is a multi-pass chloroplast thylakoid membrane protein.
POPTR	psaA	IPR001280,IPR006243	GO:0016020	membrane	MODIFY	yes	GO:0009535 chloroplast thylakoid membrane	Use the specific chloroplast thylakoid membrane term.
POPTR	psaA	IPR006243	GO:0046872	metal ion binding	MODIFY	yes	GO:0051539 4 iron, 4 sulfur cluster binding	The UniProt entry describes the FX 4Fe-4S iron-sulfur center bound by the PSI reaction center.
POPTR	psaB	IPR006244	GO:0009522	photosystem I	ACCEPT	no		The reviewed entry describes PsaA/PsaB as the PSI reaction-center heterodimer.
POPTR	psaB	IPR001280,IPR006244	GO:0009579	thylakoid	MODIFY	yes	GO:0009535 chloroplast thylakoid membrane	Use the specific chloroplast thylakoid membrane term.
POPTR	psaB	IPR001280,IPR006244	GO:0016020	membrane	MODIFY	yes	GO:0009535 chloroplast thylakoid membrane	Use the specific chloroplast thylakoid membrane term.
POPTR	psaC	IPR017491	GO:0009522	photosystem I	ACCEPT	no		The reviewed entry describes PsaC as a PSI iron-sulfur center subunit.
POPTR	psaC	IPR017491	GO:0009773	photosynthetic electron transport in photosystem I	ACCEPT	no		PsaC is the terminal Fe-S electron acceptor of PSI and donates electrons to ferredoxin.
POPTR	psaC	IPR017491	GO:0042651	thylakoid membrane	MODIFY	yes	GO:0009535 chloroplast thylakoid membrane	Use the specific chloroplast thylakoid membrane location.
POPTR	psaC	IPR017491	GO:0051539	4 iron, 4 sulfur cluster binding	ACCEPT	no		PsaC binds two 4Fe-4S clusters that serve as PSI electron acceptors FA and FB.
POPTR	psaJ	IPR002615,IPR036062	GO:0009522	photosystem I	ACCEPT	no		The reviewed entry identifies the protein as photosystem I reaction center subunit IX and describes an organizing role for PsaE/PsaF.
POPTR	psbA	IPR000484,IPR036854	GO:0009772	photosynthetic electron transport in photosystem II	ACCEPT	no		PsbA is directly involved in PSII electron transport.
POPTR	psbA	IPR000484,IPR036854	GO:0019684	photosynthesis, light reaction	ACCEPT	no		This process-level term is appropriate for a core thylakoid reaction-center subunit.
POPTR	psbB	IPR000932,IPR036001	GO:0009521	photosystem	MODIFY	yes	GO:0009523 photosystem II	Use the specific photosystem II complex term.
POPTR	psbB	IPR017486	GO:0009523	photosystem II	ACCEPT	no		The reviewed entry describes CP47 as one component of the PSII core complex.
POPTR	psbB	IPR000932,IPR036001	GO:0009767	photosynthetic electron transport chain	MODIFY	yes	GO:0009772 photosynthetic electron transport in photosystem II	CP47 is a PSII core subunit, so the PSII-specific process term is preferred.
POPTR	psbB	IPR017486	GO:0009772	photosynthetic electron transport in photosystem II	ACCEPT	no		CP47 helps catalyze the primary photochemical processes of PSII.
POPTR	psbB	IPR000932,IPR017486,IPR036001	GO:0016020	membrane	MODIFY	yes	GO:0009535 chloroplast thylakoid membrane	Use the specific chloroplast thylakoid membrane location.
POPTR	psbB	IPR000932,IPR036001	GO:0019684	photosynthesis, light reaction	ACCEPT	no		PsbB participates in light-induced PSII photochemistry.
POPTR	psbC	IPR000932,IPR036001	GO:0009521	photosystem	MODIFY	yes	GO:0009523 photosystem II	Use the specific photosystem II complex term.
POPTR	psbC	IPR005869	GO:0009523	photosystem II	ACCEPT	no		The reviewed entry describes CP43 as one component of the PSII core complex.
POPTR	psbC	IPR000932,IPR036001	GO:0009767	photosynthetic electron transport chain	MODIFY	yes	GO:0009772 photosynthetic electron transport in photosystem II	CP43 is a PSII core subunit, so the PSII-specific process term is preferred.
POPTR	psbC	IPR005869	GO:0009772	photosynthetic electron transport in photosystem II	ACCEPT	no		CP43 helps catalyze the primary photochemical processes of PSII.
POPTR	psbC	IPR000932,IPR005869,IPR036001	GO:0016020	membrane	MODIFY	yes	GO:0009535 chloroplast thylakoid membrane	Use the specific chloroplast thylakoid membrane location.
POPTR	psbC	IPR000932,IPR036001	GO:0019684	photosynthesis, light reaction	ACCEPT	no		PsbC participates in light-induced PSII photochemistry.
POPTR	psbD	IPR005868	GO:0009523	photosystem II	ACCEPT	no		The D1/D2 reaction-center heterodimer is part of the PSII complex.
POPTR	psbD	IPR000484,IPR036854	GO:0009772	photosynthetic electron transport in photosystem II	ACCEPT	no		PsbD is part of the PSII reaction center that drives water-plastoquinone electron transport.
POPTR	psbD	IPR005868	GO:0016020	membrane	MODIFY	yes	GO:0009535 chloroplast thylakoid membrane	Use the specific chloroplast thylakoid membrane term.
POPTR	psbD	IPR000484,IPR005868,IPR036854	GO:0019684	photosynthesis, light reaction	ACCEPT	no		PsbD participates in the light-driven water:plastoquinone oxidoreductase reaction.
POPTR	psbI	IPR003686	GO:0009523	photosystem II	ACCEPT	no		The reviewed entry describes PsbI as one component of the PSII core complex.
POPTR	psbI	IPR003686	GO:0009539	photosystem II reaction center	ACCEPT	no		The reviewed entry identifies PsbI as photosystem II reaction center protein I and a PSII core-complex component.
POPTR	psbI	IPR003686	GO:0016020	membrane	MODIFY	yes	GO:0009535 chloroplast thylakoid membrane	Use the specific chloroplast thylakoid membrane term.
POPTR	psbJ	IPR002682	GO:0009523	photosystem II	ACCEPT	no		The reviewed entry describes PsbJ as one component of the PSII core complex.
POPTR	psbJ	IPR002682	GO:0009539	photosystem II reaction center	ACCEPT	no		The reviewed entry identifies PsbJ as a photosystem II reaction center protein and core-complex component.
POPTR	psbJ	IPR002682	GO:0016020	membrane	MODIFY	yes	GO:0009535 chloroplast thylakoid membrane	Use the specific chloroplast thylakoid membrane term supported by UniProt.
POPTR	psbL	IPR003372	GO:0009523	photosystem II	ACCEPT	no		The reviewed entry describes PsbL as one component of the PSII core complex.
POPTR	psbL	IPR003372	GO:0009539	photosystem II reaction center	ACCEPT	no		The reviewed entry identifies PsbL as photosystem II reaction center protein L and a PSII core-complex component.
POPTR	psbL	IPR003372	GO:0016020	membrane	MODIFY	yes	GO:0009535 chloroplast thylakoid membrane	Use the specific chloroplast thylakoid membrane term.
POPTR	psbM	IPR007826	GO:0009523	photosystem II	ACCEPT	no		The reviewed entry describes PsbM as one component of the PSII core complex.
POPTR	psbM	IPR007826	GO:0016020	membrane	MODIFY	yes	GO:0009535 chloroplast thylakoid membrane	Use the specific chloroplast thylakoid membrane term.
POPTR	psbM	IPR007826,IPR037269	GO:0019684	photosynthesis, light reaction	ACCEPT	no		PsbM is part of PSII, which performs light-driven water:plastoquinone oxidoreduction.
POPTR	psbN	IPR003398	GO:0015979	photosynthesis	KEEP_AS_NON_CORE	yes		UniProt says PsbN may play a role in photosystem I and II biogenesis, but also cautions that it is probably not a PSII component.
POPTR	psbN	IPR003398	GO:0016020	membrane	MODIFY	yes	GO:0009535 chloroplast thylakoid membrane	Use the specific chloroplast thylakoid membrane localization supported by UniProt.
POPTR	rpl14	IPR000218,IPR005745,IPR036853	GO:0003735	structural constituent of ribosome	ACCEPT	no		rpl14 is a conserved chloroplast 50S/large-subunit ribosomal protein.
POPTR	rpl14	IPR000218,IPR036853	GO:0005840	ribosome	KEEP_AS_NON_CORE	yes		Retain the generic ribosome annotation as non-core because GO:0015934 is more precise for a 50S/large-subunit protein.
POPTR	rpl14	IPR005745	GO:0015934	large ribosomal subunit	ACCEPT	no		The reviewed entry identifies uL14c as a chloroplast 50S/large-subunit ribosomal protein.
POPTR	rpl16	IPR000114,IPR016180,IPR020798,IPR036920	GO:0003735	structural constituent of ribosome	ACCEPT	no		rpl16 encodes a conserved chloroplast large-subunit ribosomal protein.
POPTR	rpl16	IPR016180,IPR020798,IPR036920	GO:0005840	ribosome	KEEP_AS_NON_CORE	yes		Retain the generic ribosome annotation as non-core because GO:0015934 is more precise for a 50S/large-subunit protein.
POPTR	rpl16	IPR000114	GO:0019843	rRNA binding	ACCEPT	no		The IBA/InterPro annotations and ribosomal-subunit identity support rRNA binding as a core ribosomal feature.
POPTR	rpl2-A	IPR005880	GO:0003723	RNA binding	MODIFY	yes	GO:0070180 large ribosomal subunit rRNA binding	rpl2 is a large ribosomal subunit protein with a ribosomal RNA-binding domain; use the specific large-subunit rRNA binding term.
POPTR	rpl2-A	IPR002171,IPR005880,IPR022666,IPR022669,IPR022671	GO:0003735	structural constituent of ribosome	ACCEPT	no		rpl2 encodes a conserved chloroplast large-subunit ribosomal protein.
POPTR	rpl2-A	IPR002171,IPR022666,IPR022669,IPR022671	GO:0005840	ribosome	KEEP_AS_NON_CORE	yes		The more specific large ribosomal subunit term captures the core complex.
POPTR	rpl2-A	IPR005880	GO:0015934	large ribosomal subunit	ACCEPT	no		The protein is a chloroplast 50S/large-subunit ribosomal protein.
POPTR	rpl2-A	IPR005880	GO:0016740	transferase activity	MARK_AS_OVER_ANNOTATED	yes		The large ribosomal subunit/rRNA catalyzes peptide-bond formation; UniProt supports rpl2 as a structural/rRNA-binding ribosomal protein rather than an individual transferase enzyme.
POPTR	rpl20	IPR005813	GO:0003735	structural constituent of ribosome	ACCEPT	no		rpl20 is a conserved 50S/large-subunit ribosomal protein.
POPTR	rpl20	IPR005813	GO:0005840	ribosome	KEEP_AS_NON_CORE	yes		Retain the generic ribosome annotation as non-core because GO:0015934 is more precise for this 50S/large-subunit protein.
POPTR	rpl20	IPR005813	GO:0006412	translation	KEEP_AS_NON_CORE	yes		Retain translation as broad ribosomal context, but do not make it core because UniProt explicitly says L20 is not involved in the protein-synthesizing functions of the subunit; the Populus entry is homology-inferred, so future Populus-specific data could refine this.
POPTR	rpl22	IPR001063,IPR005727,IPR018260,IPR036394,IPR047867	GO:0003735	structural constituent of ribosome	ACCEPT	no		The reviewed entry identifies the protein as a conserved chloroplast ribosomal subunit protein.
POPTR	rpl22	IPR001063,IPR018260,IPR036394	GO:0005840	ribosome	KEEP_AS_NON_CORE	yes		Retain the generic ribosome annotation as non-core because the small/large ribosomal subunit term is more precise for this protein.
POPTR	rpl22	IPR005727,IPR047867	GO:0015934	large ribosomal subunit	ACCEPT	no		The reviewed entry identifies this as a chloroplast small/large ribosomal subunit protein.
POPTR	rpl33	IPR001705,IPR018264	GO:0003735	structural constituent of ribosome	ACCEPT	no		rpl33 encodes a conserved chloroplast 50S/large-subunit ribosomal protein.
POPTR	rpl33	IPR001705,IPR018264	GO:0005840	ribosome	KEEP_AS_NON_CORE	yes		Retain the generic ribosome annotation as non-core because GO:0015934 is more precise for a 50S/large-subunit protein.
POPTR	rpl36	IPR000473,IPR035977	GO:0003735	structural constituent of ribosome	ACCEPT	no		rpl36 encodes a conserved chloroplast large-subunit ribosomal protein.
POPTR	rpl36	IPR000473,IPR035977	GO:0005840	ribosome	KEEP_AS_NON_CORE	yes		Retain the generic ribosome annotation as non-core because GO:0015934 is more precise for a 50S/large-subunit protein.
POPTR	rpoA	IPR011262,IPR036603	GO:0046983	protein dimerization activity	KEEP_AS_NON_CORE	yes		Retain as non-core; the central role is contribution to plastid RNA polymerase activity.
POPTR	rpoB	IPR015712	GO:0032549	ribonucleoside binding	KEEP_AS_NON_CORE	yes		Keep as non-core; the more informative molecular role is contribution to DNA-directed RNA polymerase activity.
POPTR	rps11	IPR001971,IPR019981,IPR036967	GO:0003735	structural constituent of ribosome	ACCEPT	no		rps11 encodes a conserved chloroplast small-subunit ribosomal protein.
POPTR	rps11	IPR001971,IPR019981,IPR036967	GO:0005840	ribosome	KEEP_AS_NON_CORE	yes		Retain the generic ribosome annotation as non-core because GO:0015935 is more precise for a 30S/small-subunit protein.
POPTR	rps12-A	IPR005679,IPR006032	GO:0003735	structural constituent of ribosome	ACCEPT	no		The reviewed entry identifies the protein as a conserved chloroplast ribosomal subunit protein.
POPTR	rps12-A	IPR006032	GO:0005840	ribosome	KEEP_AS_NON_CORE	yes		Retain the generic ribosome annotation as non-core because the small/large ribosomal subunit term is more precise for this protein.
POPTR	rps12-A	IPR005679	GO:0015935	small ribosomal subunit	ACCEPT	no		The reviewed entry identifies this as a chloroplast small/large ribosomal subunit protein.
POPTR	rps12-B	IPR005679,IPR006032	GO:0003735	structural constituent of ribosome	ACCEPT	no		rps12-B is a conserved chloroplast small-subunit ribosomal protein.
POPTR	rps12-B	IPR006032	GO:0005840	ribosome	KEEP_AS_NON_CORE	yes		Retain the generic ribosome annotation as non-core because the small-ribosomal-subunit term is more precise.
POPTR	rps12-B	IPR005679	GO:0015935	small ribosomal subunit	ACCEPT	no		The term correctly captures its ribosomal-complex context.
POPTR	rps14	IPR001209,IPR018271	GO:0003735	structural constituent of ribosome	ACCEPT	no		rps14 is a conserved chloroplast small-subunit ribosomal protein.
POPTR	rps14	IPR001209,IPR018271	GO:0005840	ribosome	KEEP_AS_NON_CORE	yes		Retain the generic ribosome annotation as non-core because the small-ribosomal-subunit term is more precise.
POPTR	rps15	IPR000589,IPR005290	GO:0003735	structural constituent of ribosome	ACCEPT	no		rps15 encodes a conserved chloroplast small-subunit ribosomal protein.
POPTR	rps15	IPR000589,IPR005290	GO:0005840	ribosome	KEEP_AS_NON_CORE	yes		The protein is a chloroplast small-subunit ribosomal protein; the new small ribosomal subunit term is more informative.
POPTR	rps18	IPR001648,IPR018275	GO:0003735	structural constituent of ribosome	ACCEPT	no		The reviewed entry identifies the protein as a conserved chloroplast ribosomal subunit protein.
POPTR	rps18	IPR001648,IPR018275	GO:0005840	ribosome	KEEP_AS_NON_CORE	yes		Retain the generic ribosome annotation as non-core because the small/large ribosomal subunit term is more precise for this protein.
POPTR	rps19-1	IPR020934	GO:0003723	RNA binding	MODIFY	yes	GO:0070181 small ribosomal subunit rRNA binding	UniProt states that S19 forms a complex with S13 that binds 16S rRNA; the ribosomal context is more specific than generic RNA binding, so this row and the rRNA binding row should yield a single GO:0070181 replacement annotation rather than duplicate downstream annotations.
POPTR	rps19-1	IPR002222,IPR005732,IPR023575	GO:0003735	structural constituent of ribosome	ACCEPT	no		rps19 encodes a conserved chloroplast small-subunit ribosomal protein.
POPTR	rps19-1	IPR002222,IPR023575	GO:0005840	ribosome	KEEP_AS_NON_CORE	yes		The protein is a small-subunit ribosomal component; the more specific small ribosomal subunit term captures the core complex.
POPTR	rps19-1	IPR005732	GO:0015935	small ribosomal subunit	ACCEPT	no		The protein is a chloroplast 30S/small-subunit ribosomal protein.
POPTR	rps2	IPR001865,IPR005706,IPR018130	GO:0003735	structural constituent of ribosome	ACCEPT	no		The reviewed entry identifies the protein as a conserved chloroplast ribosomal subunit protein.
POPTR	rps2	IPR001865,IPR018130	GO:0005840	ribosome	KEEP_AS_NON_CORE	yes		Retain the generic ribosome annotation as non-core because the small/large ribosomal subunit term is more precise for this protein.
POPTR	rps2	IPR005706	GO:0015935	small ribosomal subunit	ACCEPT	no		The reviewed entry identifies this as a chloroplast small/large ribosomal subunit protein.
POPTR	rps3	IPR004044,IPR009019	GO:0003723	RNA binding	MODIFY	yes	GO:0019843 rRNA binding	Use rRNA binding as the more informative ribosomal RNA-specific function.
POPTR	rps3	IPR001351,IPR005704	GO:0003735	structural constituent of ribosome	ACCEPT	no		The reviewed entry identifies the protein as a conserved chloroplast ribosomal subunit protein.
POPTR	rps4	IPR002942,IPR036986	GO:0003723	RNA binding	MODIFY	yes	GO:0019843 rRNA binding	Use the more informative rRNA binding term; the separate mRNA binding transfer is retained only as non-core.
POPTR	rps4	IPR005709	GO:0003735	structural constituent of ribosome	ACCEPT	no		Rps4 is a conserved small-subunit ribosomal protein.
POPTR	rps4	IPR005709	GO:0015935	small ribosomal subunit	ACCEPT	no		The term correctly captures its ribosomal-complex location.
POPTR	rps7	IPR020606	GO:0003723	RNA binding	KEEP_AS_NON_CORE	yes		The specific and well-supported function is rRNA binding (GO:0019843); the generic RNA binding parent is true but redundant with it, so it is kept as a non-core annotation.
POPTR	rps7	IPR005717,IPR020606	GO:0003735	structural constituent of ribosome	ACCEPT	no		This is the core molecular function of the protein as a member of the universal uS7 ribosomal protein family.
POPTR	rps7	IPR005717	GO:0015935	small ribosomal subunit	ACCEPT	no		UniProt states the protein is part of the 30S ribosomal subunit and nucleates the 30S head domain.
POPTR	rps8	IPR000630,IPR035987	GO:0003735	structural constituent of ribosome	ACCEPT	no		rps8 encodes a conserved chloroplast small-subunit ribosomal protein.
POPTR	rps8	IPR000630,IPR035987	GO:0005840	ribosome	KEEP_AS_NON_CORE	yes		Retain the generic ribosome annotation as non-core because GO:0015935 is more precise for a 30S/small-subunit protein.
POPTR	ycf2-1	IPR003959	GO:0005524	ATP binding	ACCEPT	no		UniProt describes Ycf2 as a probable ATPase and includes P-loop/AAA ATPase signatures.
POPTR	ycf2-1	IPR003959	GO:0016887	ATP hydrolysis activity	ACCEPT	no		UniProt calls Ycf2 a probable ATPase and InterPro supports ATP hydrolysis activity.
POPTR	ycf4	IPR003359	GO:0009522	photosystem I	REMOVE	yes		Ycf4 is a photosystem I assembly factor rather than a structural PSI component; the biological role is represented separately by the NEW GO:0048564 photosystem I assembly annotation.
POPTR	ycf4	IPR003359	GO:0009579	thylakoid	MODIFY	yes	GO:0009535 chloroplast thylakoid membrane	Use the specific chloroplast thylakoid membrane location.
POPTR	ycf4	IPR003359	GO:0016020	membrane	MODIFY	yes	GO:0009535 chloroplast thylakoid membrane	Use the specific chloroplast thylakoid membrane term.
PSEAE	ftsI	IPR037532	GO:0008955	peptidoglycan glycosyltransferase activity	REMOVE	yes		This is a clear mis-annotation. FtsI/PBP3 is a monofunctional D,D-transpeptidase and FtsW (not FtsI) provides the glycan polymerase activity. Class B PBPs by definition lack the N-terminal glycosyltransferase domain found in Class A PBPs. This annotation should be removed as it represents a significant functional error.
PSEAE	pbpC	IPR037532	GO:0008955	peptidoglycan glycosyltransferase activity	REMOVE	yes		This is a clear annotation error. PbpC belongs to the FtsI/PBP3 subfamily of Class B (monofunctional) penicillin-binding proteins. The deep research confirms PbpC is a class B PBP predicted to catalyze D,D-transpeptidation. Class B PBPs possess only the transpeptidase domain. Peptidoglycan glycosyltransferase activity (GO:0008955) is found in Class A PBPs (e.g., PBP1a, PBP1b in E. coli), which have both glycosyltransferase and transpeptidase domains.
PSEAE	pqsB	IPR016039	GO:0016746	acyltransferase activity	MARK_AS_OVER_ANNOTATED	yes		Attributing the catalytic MF to the non-catalytic subunit over-annotates PqsB. PqsB contributes to (is required for) the activity of the PqsBC complex but does not itself catalyze acyl transfer; a contributes_to qualifier, or annotation of the activity to the PqsBC complex, would be more accurate.
PSEAE	pqsC	IPR013751	GO:0004315	3-oxoacyl-[acyl-carrier-protein] synthase activity	MODIFY	yes	GO:0016747 acyltransferase activity, transferring groups other than amino-acyl groups	The fold-based prediction picks the wrong specific activity. The accurate activity is an acyl transfer (not a 3-oxoacyl-ACP/fatty-acid synthase reaction). Replace with the accurate parent GO:0016747 and propose a specific new term for EC 2.3.1.230 (see proposed_new_terms).
PSEAE	pqsC	IPR013751	GO:0006633	fatty acid biosynthetic process	REMOVE	yes		Demonstrably incorrect biological process. The enzyme consumes a fatty acyl substrate but synthesizes an alkylquinolone; assigning fatty acid biosynthesis is a domain-propagation error.
PSEAE	pqsC	IPR016039	GO:0016746	acyltransferase activity	ACCEPT	no		Correct general molecular function (true parent of the specific HHQ-synthase activity). Retained as an accurate, if non-specific, MF.
PSEAE	rhlB	IPR011545	GO:0003676	nucleic acid binding	REMOVE	yes		This term is overly broad. RhlB specifically binds RNA substrates, not DNA or other nucleic acids, making the RNA binding annotation (GO:0003723) more appropriate and informative.
PSEAE	rpsD	IPR002942,IPR036986	GO:0003723	RNA binding	KEEP_AS_NON_CORE	yes		The S4 RNA-binding domain does indeed confer RNA binding activity. However, the more specific rRNA binding (GO:0019843) is already annotated via IBA and IEA evidence. This general RNA binding annotation is redundant with the more specific term but not incorrect; uS4 also has mRNA binding activity as a translational autorepressor in E. coli.
PSEAE	rpsD	IPR005709	GO:0003735	structural constituent of ribosome	ACCEPT	no		Correct InterPro2GO mapping. The bacterial uS4 family (IPR005709) appropriately maps to structural constituent of ribosome. Consistent with the IBA annotation above.
PSEAE	rpsD	IPR005709	GO:0015935	small ribosomal subunit	ACCEPT	no		Correct InterPro2GO mapping consistent with all structural and biochemical evidence for 30S subunit localization.
PSEAE	secF	IPR005665	GO:0006886	intracellular protein transport	KEEP_AS_NON_CORE	yes		Correct but general. The term captures the overall transport function but does not specify the Sec pathway or the PMF-dependent mechanism. More specific terms are available and already annotated.
PSEAE	secF	IPR005665	GO:0015450	protein-transporting ATPase activity	MODIFY	yes	GO:0009977 proton motive force dependent protein transmembrane transporter activity	SecF/SecDF is explicitly not an ATPase. Multiple structural and biochemical studies demonstrate that SecDF uses the proton motive force, not ATP hydrolysis, to enhance translocation. Tsukazaki et al. (2011) identified an ATP-independent translocation step requiring SecDF and PMF. The appropriate MF term is GO:0009977 (proton motive force dependent protein transmembrane transporter activity), as SecDF conducts protons coupled to polypeptide movement. SecF contributes to the translocase complex activity but does not independently enable ATPase activity.
PSEAE	ubiE	IPR004033,IPR023576	GO:0008168	methyltransferase activity	MODIFY	yes	GO:0008425 2-methoxy-6-polyprenyl-1,4-benzoquinol methyltransferase activity; GO:0043770 demethylmenaquinone methyltransferase activity	Correct but too general. The more specific terms GO:0008425 (2-methoxy-6-polyprenyl-1,4-benzoquinol methyltransferase activity) and GO:0043770 (demethylmenaquinone methyltransferase activity) are already present and more informative.
PSEAI	merA	IPR012999	GO:0016668	oxidoreductase activity, acting on a sulfur group of donors, NAD(P) as acceptor	REMOVE	yes		Misleading - MerA acts on mercury ions as substrate, not sulfur groups. The redox-active cysteines are part of the enzyme mechanism, not the substrate.
PSEAI	merA	IPR021179	GO:0045340	mercury ion binding	ACCEPT	no		Structural and mutational evidence confirms mercury binding as essential molecular function
PSEAI	merA	IPR021179	GO:0050661	NADP binding	ACCEPT	no		NADPH binding is essential for electron donation in mercury reduction
PSEAI	merA	IPR021179	GO:0050787	detoxification of mercury ion	ACCEPT	no		Core biological function with extensive genetic and phenotypic evidence
PSEAI	strB	IPR006748	GO:0016773	phosphotransferase activity, alcohol group as acceptor	MODIFY	yes	GO:0034071 aminoglycoside phosphotransferase activity	Replace the broad or over-specific electronic term 'phosphotransferase activity, alcohol group as acceptor' with aminoglycoside phosphotransferase activity based on UniProt/CARD determinant identity and the curated ARO->GO mapping.
PSEAI	strB	IPR006748	GO:0019748	secondary metabolic process	MODIFY	yes	GO:0046677 response to antibiotic	The more informative process is response to antibiotic; the molecular activity should be captured by aminoglycoside phosphotransferase activity.
PSEPK	BenR	IPR018060,IPR018062	GO:0003700	DNA-binding transcription factor activity	MODIFY	yes	GO:0001216 DNA-binding transcription activator activity; GO:0141097 ligand-modulated transcription activator activity	This annotation correctly captures the core function of BenR as a transcription factor. However, a more specific child term 'DNA-binding transcription activator activity' (GO:0001216) or 'ligand-modulated transcription activator activity' (GO:0141097) would be more precise given that BenR is an activator (not repressor) and is regulated by benzoate binding.
PSEPK	BenR	IPR018060,IPR018062	GO:0043565	sequence-specific DNA binding	ACCEPT	no		This annotation is correct and more specific than GO:0003677. BenR recognizes specific direct repeat sequences (TGCA-N6-GGNTA motifs) in the benA promoter and related promoters, as demonstrated by DNase I footprinting. This is a core molecular function.
PSEPK	PP_0635	IPR000123	GO:0003723	RNA binding	ACCEPT	no		"Group II intron RT/maturases bind specifically to their intron RNA as part of ribonucleoprotein (RNP) assembly. This binding is essential for maturase activity (promoting intron folding and splicing) and for retrohoming/retrotransposition. The annotation is appropriately broad and supported by the domain architecture. [Gapinska et al. 2024, NAR: ""group II intron maturases are associated with intron RNA splicing/mobility""]"
PSEPK	PP_0635	IPR000123	GO:0006278	RNA-templated DNA biosynthetic process	MODIFY	yes	GO:0006315 homing of group II introns; GO:0000373 Group II intron splicing	While the annotation is not incorrect (the protein does perform RNA-templated DNA biosynthesis), a more specific term would better capture the biological context. The RT activity in group II intron maturases specifically functions in retrotransposition/retrohoming of the intron element. GO:0032197 (retrotransposition) or GO:0006315 (homing of group II introns) would be more informative.
PSEPK	PP_1084	IPR000866	GO:0016209	antioxidant activity	MARK_AS_OVER_ANNOTATED	yes		The annotation should prioritize the direct enzymatic activity rather than a generic antioxidant-function parent.
PSEPK	PP_1084	IPR000866	GO:0016491	oxidoreductase activity	MARK_AS_OVER_ANNOTATED	yes		The specific peroxide-reduction terms are available and should carry the functional interpretation.
PSEPK	PP_1084	IPR019479	GO:0051920	peroxiredoxin activity	ACCEPT	no		UniProt identifies the protein as a thioredoxin peroxidase/peroxiredoxin family member that reduces peroxides, and the KT2440-specific study confirms typical 2-Cys peroxiredoxin classification.
PSEPK	accC	IPR004549	GO:0016874	ligase activity	KEEP_AS_NON_CORE	yes		"Biotin carboxylase is an ATP-dependent ligase (EC class 6, carbon-nitrogen ligase forming the carboxybiotin), supported by InterPro IPR004549 (Acetyl_CoA_COase_biotin_COase) and the UniProt Ligase keyword. However ""ligase activity"" is a broad parent of the more specific biotin carboxylase activity (GO:0004075) already annotated. Keeping as non-core to avoid redundancy with the precise term."
PSEPK	accC	IPR011761	GO:0046872	metal ion binding	KEEP_AS_NON_CORE	yes		Biotin carboxylase requires a divalent metal ion (Mg2+) to coordinate ATP in the ATP-grasp active site, consistent with the UniProt Magnesium/Metal-binding keywords and InterPro IPR011761 (ATP-grasp). The term is correct but a broad parent; keeping as non-core supporting function.
PSEPK	aceA	IPR018523,IPR039556	GO:0003824	catalytic activity	MODIFY	yes	GO:0004451 isocitrate lyase activity	aceA is isocitrate lyase (EC 4.1.3.1); the generic 'catalytic activity' term should be replaced by the specific activity, which is independently annotated here (GO:0004451 isocitrate lyase activity).
PSEPK	aceK	IPR010452	GO:0006006	glucose metabolic process	MARK_AS_OVER_ANNOTATED	yes		The functional context of AceK is the glyoxylate-bypass switch during growth on C2/fatty-acid substrates, not glucose metabolism. The glucose metabolic process term is over-broad and misleading.
PSEPK	aceK	IPR010452	GO:0016791	phosphatase activity	MODIFY	yes	GO:0101014 [isocitrate dehydrogenase (NADP+)] phosphatase activity	The specific IDH phosphatase term precisely captures the reactivating dephosphorylation of isocitrate dehydrogenase, whereas the bare phosphatase term is uninformative.
PSEPK	ada	IPR004026	GO:0003677	DNA binding	ACCEPT	no		DNA binding is a core function of Ada, required for both its enzymatic DNA repair activity and its transcriptional regulatory function. This general term is appropriate as a parent term given the more specific annotations for sequence-specific binding.
PSEPK	ada	IPR018060	GO:0003700	DNA-binding transcription factor activity	ACCEPT	no		Transcriptional activation is a core function of Ada. The protein contains a HTH AraC-type DNA-binding domain and directly activates transcription of the alkA-ada operon in response to alkylation damage. This is a well-characterized bifunctional property of Ada proteins across bacteria.
PSEPK	ada	IPR014048	GO:0003824	catalytic activity	MARK_AS_OVER_ANNOTATED	yes		While technically correct, this term is too general and does not provide informative annotation. The more specific GO:0003908 (methylated-DNA-[protein]-cysteine S-methyltransferase activity) is already annotated and provides the precise molecular function. Keeping this very broad term adds no value.
PSEPK	ada	IPR004026,IPR018060	GO:0006355	regulation of DNA-templated transcription	MODIFY	yes	GO:0045893 positive regulation of DNA-templated transcription	While Ada does regulate transcription, it specifically acts as a positive regulator (activator). The more specific term GO:0045893 (positive regulation of DNA-templated transcription) would be more accurate and informative.
PSEPK	ada	IPR004026	GO:0008270	zinc ion binding	ACCEPT	no		Zinc binding is a core property of the Ada N-terminal domain. The zinc-coordinating cysteine cluster is conserved across Ada proteins and is essential for the methylphosphotriester repair function. UniProt provides direct evidence for zinc-binding residues in this protein.
PSEPK	ada	IPR018060	GO:0043565	sequence-specific DNA binding	ACCEPT	no		Sequence-specific DNA binding is a core function of Ada for its transcriptional regulatory activity. The protein specifically recognizes and binds to Ada box motifs in target promoters, as demonstrated by mutational analysis showing that deletion of these motifs abolishes Ada-dependent induction.
PSEPK	ada		GO:0006307	DNA alkylation repair	NEW	no		"This is the most appropriate biological process term for Ada's repair function. Ada is a DNA alkyltransferase that specifically repairs alkylation damage, and this term should be annotated in addition to or instead of the general ""DNA repair"" term."
PSEPK	ada		GO:0035510	DNA dealkylation	NEW	no		"This term precisely describes the biochemical process that Ada performs: removing alkyl (methyl) groups from nucleotides in DNA. This should replace the misleading ""methylation"" annotation."
PSEPK	ada		GO:0045893	positive regulation of DNA-templated transcription	NEW	no		"This term is more specific than the general ""regulation of DNA-templated transcription"" and accurately describes Ada's activator function. Ada specifically activates (positively regulates) transcription of its target genes."
PSEPK	ahpC	IPR000866	GO:0016209	antioxidant activity	KEEP_AS_NON_CORE	yes		The annotation is not wrong, but it should not be treated as the primary functional statement when more specific child terms are available.
PSEPK	ahpC	IPR000866	GO:0016491	oxidoreductase activity	MODIFY	yes	GO:0051920 peroxiredoxin activity	A more specific molecular-function term should replace this overly broad parent annotation.
PSEPK	algA	IPR001538,IPR006375	GO:0016779	nucleotidyltransferase activity	MARK_AS_OVER_ANNOTATED	yes		GO:0004475 already captures the exact catalytic activity. The generic nucleotidyltransferase parent is redundant and not informative enough to represent core function.
PSEPK	algA	IPR006375	GO:0000271	polysaccharide biosynthetic process	MARK_AS_OVER_ANNOTATED	yes		The more direct process assignment is GO:0009298 GDP-mannose biosynthetic process. This broader term overstates the level of direct evidence for generic polysaccharide biosynthesis.
PSEPK	algA	IPR001538	GO:0005976	polysaccharide metabolic process	MARK_AS_OVER_ANNOTATED	yes		The evidence supports precursor synthesis in GDP-mannose metabolism, not a generic polysaccharide metabolic role. The more direct core process is GO:0009298.
PSEPK	algD	IPR001732,IPR014026,IPR014027	GO:0051287	NAD binding	ACCEPT	no		This annotation is correct as a supporting molecular function. AlgD is an NAD-dependent dehydrogenase with an N-terminal Rossmann-like nucleotide-binding domain, and the UniProt record lists multiple NAD(+) binding residues. This term is less informative than the catalytic activity term but remains valid.
PSEPK	alr	IPR009006	GO:0003824	catalytic activity	MARK_AS_OVER_ANNOTATED	yes		Specific racemase annotations should be used instead.
PSEPK	alr	IPR043698	GO:0016853	isomerase activity	MARK_AS_OVER_ANNOTATED	yes		Specific racemase terms are already present.
PSEPK	ampC	IPR001586	GO:0017001	antibiotic catabolic process	MODIFY	yes	GO:0030655 beta-lactam antibiotic catabolic process	While AmpC does participate in antibiotic catabolism, it specifically catabolizes beta-lactam antibiotics. The more specific term GO:0030655 beta-lactam antibiotic catabolic process (defined as chemical reactions and pathways resulting in the breakdown of a beta-lactam antibiotic) precisely describes AmpC's biological process. Literature confirms substrate specificity for penicillins and cephalosporins.
PSEPK	ampC	IPR001586	GO:0030288	outer membrane-bounded periplasmic space	ACCEPT	no		This cellular component annotation is correct. AmpC functions in the periplasm where it can hydrolyze beta-lactam antibiotics before they reach their targets (penicillin-binding proteins on the inner membrane). The signal peptide and periplasmic localization are essential for the resistance mechanism. This represents a core aspect of AmpC function.
PSEPK	amtB	IPR001905,IPR018047,IPR024041	GO:0016020	membrane	KEEP_AS_NON_CORE	yes		GO:0016020 (membrane) is a true but high-level parent of the more informative GO:0005886 (plasma membrane) annotation already present. It is an InterPro2GO electronic inference that is not incorrect, but adds little specificity; retained as non-core.
PSEPK	aqpZ	IPR000425	GO:0015267	channel activity	MARK_AS_OVER_ANNOTATED	yes		GO:0015250 captures the substrate-specific channel function and should be preferred over the broad channel-activity parent.
PSEPK	aqpZ	IPR000425,IPR023743	GO:0016020	membrane	MARK_AS_OVER_ANNOTATED	yes		GO:0005886 is a more informative location for this bacterial inner-membrane channel.
PSEPK	aqpZ	IPR000425,IPR023743	GO:0055085	transmembrane transport	MARK_AS_OVER_ANNOTATED	yes		GO:0006833 captures the substrate-specific transport process for AqpZ.
PSEPK	aroA	IPR013792	GO:0003824	catalytic activity	MARK_AS_OVER_ANNOTATED	yes		GO:0003824 is the top-level molecular-function catalytic term and conveys no specific information. The protein has well-supported specific activities (EPSP synthase, EC 2.5.1.19; prephenate dehydrogenase, EC 1.3.1.12) that should be used instead.
PSEPK	aroA	IPR003099	GO:0004665	prephenate dehydrogenase (NADP+) activity	KEEP_AS_NON_CORE	yes		The protein carries a genuine N-terminal prephenate/arogenate dehydrogenase (TyrA) module (Pfam PDH_N/PDH_C; COG0287), so prephenate dehydrogenase activity is a plausible second function. However, UniProt's curated CATALYTIC ACTIVITY block lists only the NAD+ route (EC 1.3.1.12), and the NADP+ specificity here is purely an InterPro electronic inference (IPR003099) with no cofactor evidence. Retain as a non-core, lower-confidence activity rather than a core function.
PSEPK	aroA	IPR001986,IPR036968	GO:0016765	transferase activity, transferring alkyl or aryl (other than methyl) groups	MARK_AS_OVER_ANNOTATED	yes		High-level parent of the specific EPSP synthase activity (GO:0003866, enolpyruvyl transferase) which is retained. Redundant given the leaf term.
PSEPK	aroA	IPR046826	GO:0070403	NAD+ binding	KEEP_AS_NON_CORE	yes		Consistent with the NAD(P)-binding Rossmann fold of the fused TyrA domain (InterPro IPR046826) and with the NAD+-dependent prephenate dehydrogenase activity. A supporting cofactor-binding term for the secondary activity, so non-core rather than a primary function.
PSEPK	aroB	IPR030963	GO:0016838	carbon-oxygen lyase activity, acting on phosphates	MARK_AS_OVER_ANNOTATED	yes		The precise activity is already captured by GO:0003856. This broad lyase grouping term adds no information beyond the specific annotation and is a less informative restatement of the same molecular function.
PSEPK	aroH	IPR002480	GO:0009073	aromatic amino acid family biosynthetic process	ACCEPT	no		"This is the canonical pathway role of a DAHP synthase and is consistent with the molecular function annotation. The term is appropriate and represents a core biological process for this gene. (The GOA stub used the label ""aromatic amino acid biosynthetic process""; the current GO label for GO:0009073 is ""aromatic amino acid family biosynthetic process"" and is used here.)"
PSEPK	benC	IPR001041,IPR036010	GO:0051536	iron-sulfur cluster binding	MARK_AS_OVER_ANNOTATED	yes		This is the broad parent of GO:0051537. BenC carries a plant-type [2Fe-2S] cluster, which is captured precisely by GO:0051537, so the generic parent should not be treated as the informative cofactor annotation.
PSEPK	benC	IPR006058	GO:0051537	2 iron, 2 sulfur cluster binding	ACCEPT	no		The 2Fe-2S cluster is part of BenC electron-transfer chemistry and supports its reductase role.
PSEPK	bena	IPR015879,IPR015881	GO:0005506	iron ion binding	ACCEPT	no		Iron ion binding is a legitimate molecular function of BenA. The Rieske [2Fe-2S] cluster requires iron for electron transfer, and the catalytic center uses a mononuclear non-heme iron for oxygen activation. While more specific terms exist for the cluster (GO:0051537, already annotated), the general iron ion binding term remains valid as an umbrella annotation. InterPro domains IPR015879 (Ring_hydroxyl_A) and IPR015881 (ARHD_Rieske_2Fe_2S) correctly identify iron-binding capacity.
PSEPK	bena	IPR001663,IPR015879,IPR015881,IPR017941,IPR036922	GO:0051537	2 iron, 2 sulfur cluster binding	ACCEPT	no		"The 2Fe-2S cluster binding annotation is well-supported by multiple domain predictions (Rieske domain at residues 47-129) and is a defining feature of the ring-hydroxylating dioxygenase alpha subunit family. The UniProt keywords explicitly include ""2Fe-2S"" and ""Iron-sulfur"". The Rieske cluster is essential for the electron transfer chain that drives the dioxygenase catalytic cycle."
PSEPK	catA	IPR000627	GO:0003824	catalytic activity	MODIFY	yes	GO:0018576 catechol 1,2-dioxygenase activity	This annotation from InterPro IPR000627 maps to the overly general catalytic activity term. The specific activity GO:0018576 (catechol 1,2-dioxygenase activity) is already annotated and correctly captures the enzymatic function: catechol + O2 = cis,cis-muconate (Rhea:RHEA:23852). The general term should be replaced with the specific one.
PSEPK	catA	IPR007535,IPR012801,IPR015889	GO:0005506	iron ion binding	MARK_AS_OVER_ANNOTATED	yes		The enzyme uses non-heme Fe(III) as cofactor (UniProt cofactor annotation: Fe(3+), ChEBI:CHEBI:29034). The more specific GO:0008199 (ferric iron binding) is already present. While iron ion binding is not incorrect, it is a less informative parent of the already-annotated ferric iron binding term and represents an over-annotation. The InterPro domains IPR007535, IPR012801, and IPR015889 that source this annotation are all intradiol dioxygenase domains that use Fe(III) specifically.
PSEPK	catA	IPR000627	GO:0008199	ferric iron binding	ACCEPT	no		Ferric iron binding is the correct and specific molecular function for the cofactor requirement of catechol 1,2-dioxygenase. The enzyme uses Fe(III) in a non-heme iron center for intradiol ring cleavage. This is well-established for the entire intradiol dioxygenase family and confirmed by the UniProt cofactor annotation (Fe(3+), ChEBI:29034).
PSEPK	catA	IPR007535	GO:0009712	catechol-containing compound metabolic process	MODIFY	yes	GO:0019614 catechol-containing compound catabolic process	The enzyme catalyzes degradation (ring cleavage) of catechol, which is specifically a catabolic process. The more specific child term GO:0019614 (catechol-containing compound catabolic process) is already annotated and more accurately represents the biological role. This general metabolic process term should be replaced with the catabolic term.
PSEPK	catA	IPR015889	GO:0016702	oxidoreductase activity, acting on single donors with incorporation of molecular oxygen, incorporation of two atoms of oxygen	MARK_AS_OVER_ANNOTATED	yes		This is a parent class of GO:0018576 (catechol 1,2-dioxygenase activity) which is already annotated. The specific term fully subsumes this general oxidoreductase classification. The IEA mapping from InterPro IPR015889 (intradiol dioxygenase core) is too general when the precise enzymatic activity is known and already annotated.
PSEPK	catA	IPR012801	GO:0019614	catechol-containing compound catabolic process	ACCEPT	no		CatA catalyzes the first step of catechol degradation in the beta-ketoadipate pathway, converting catechol to cis,cis-muconate. This is definitionally a catechol-containing compound catabolic process. The term is at the right level of specificity - more specific than the general metabolic process (GO:0009712) and complementary to the pathway term (GO:0042952).
PSEPK	catB	IPR018110	GO:0009063	amino acid catabolic process	REMOVE	yes		The annotation reflects family-level conflation rather than the specific biology of catB in P. putida KT2440.
PSEPK	catB	IPR013370	GO:0018850	chloromuconate cycloisomerase activity	REMOVE	yes		The evidence supports muconate cycloisomerase activity, not the chloromuconate-specific/dehalogenating activity of chlorocatechol pathways.
PSEPK	catB	IPR013370	GO:0030145	manganese ion binding	ACCEPT	no		Mn(2+) binding is directly connected to catalytic function and is experimentally supported for the P. putida enzyme.
PSEPK	cbrB	IPR001789	GO:0000160	phosphorelay signal transduction system	ACCEPT	no		This annotation is correct and captures a core biological process for cbrB. CbrB is the cognate response regulator in the CbrA/CbrB two-component system, and biochemical work shows phosphotransfer from CbrA to CbrB. The term remains appropriate even though the seeded evidence was only domain-based.
PSEPK	cbrB	IPR002078	GO:0005524	ATP binding	KEEP_AS_NON_CORE	yes		This annotation is likely correct because CbrB contains the characteristic AAA+ sigma-54 activator ATPase region, but it is generic and less informative than the response-regulator and transcription-activator functions. It should be retained as non-core rather than emphasized in the summary of gene function.
PSEPK	cbrB	IPR002078	GO:0006355	regulation of DNA-templated transcription	MODIFY	yes	GO:0045893 positive regulation of DNA-templated transcription	The annotation is directionally correct but too broad. CbrB is not merely a generic transcription regulator; it is a sigma-N-dependent transcriptional activator that directly activates crcZ, crcY, and a larger regulon. A more informative replacement is positive regulation of DNA-templated transcription, with carbon catabolite repression retained as a distinct downstream biological process.
PSEPK	cca	IPR002646,IPR012006	GO:0003723	RNA binding	MARK_AS_OVER_ANNOTATED	yes		The substrate is tRNA; the more specific GO:0000049 tRNA binding annotation is present and preferred. Generic RNA binding is an over-annotation here.
PSEPK	cca	IPR002646	GO:0006396	RNA processing	MARK_AS_OVER_ANNOTATED	yes		CCA addition is part of tRNA processing/repair, but the generic RNA processing term is an over-annotation given the specific GO:0001680 tRNA 3'-terminal CCA addition and GO:0042780 tRNA 3'-end processing annotations.
PSEPK	cca	IPR002646	GO:0016779	nucleotidyltransferase activity	MARK_AS_OVER_ANNOTATED	yes		The specific GO:0004810 CCA tRNA nucleotidyltransferase activity is present and preferred; the generic nucleotidyltransferase parent is an over-annotation.
PSEPK	cheA	IPR004358	GO:0016772	transferase activity, transferring phosphorus-containing groups	MARK_AS_OVER_ANNOTATED	yes		The broader transferase term is redundant once the specific protein histidine kinase activity is retained.
PSEPK	cheA	IPR004105,IPR008207,IPR036641	GO:0000160	phosphorelay signal transduction system	ACCEPT	no		The phosphorelay system is the direct mechanistic context of CheA function, and this term is specific enough to retain as a core process annotation.
PSEPK	cheA	IPR002545,IPR004105,IPR036061,IPR037006	GO:0006935	chemotaxis	ACCEPT	no		The KT2440 cheA2 mutant phenotype directly connects this paralog to the canonical chemotaxis pathway rather than only to generic signaling.
PSEPK	cheA	IPR002545,IPR036061,IPR036097	GO:0007165	signal transduction	MARK_AS_OVER_ANNOTATED	yes		GO:0007165 is a very high-level parent of the more informative phosphorelay and chemotaxis terms already present for this gene.
PSEPK	cheA	IPR004105	GO:0005737	cytoplasm	KEEP_AS_NON_CORE	yes		The annotation is not wrong, but it is too generic to represent the most informative localization context for the chemotaxis machinery.
PSEPK	cheY	IPR001789	GO:0000160	phosphorelay signal transduction system	ACCEPT	no		Directly reflects the central, well-established function of CheY as the response-regulator output of the chemotaxis phosphorelay. The InterPro-based IEA mapping is biologically appropriate and consistent with the domain architecture and with KT2440-specific evidence that CheY (PP_4340) is phosphorylated by CheA (PP_4338).
PSEPK	cheZ	IPR007439	GO:0003824	catalytic activity	MODIFY	yes	GO:0004721 phosphoprotein phosphatase activity	The InterPro2GO mapping assigns the root catalytic activity term, but CheZ has a well-defined, specific activity as a phosphoprotein phosphatase acting on phosphorylated CheY (an aspartyl-phosphate). UniProt itself maps the Protein phosphatase keyword for this entry to GO:0004721. Replace with the more specific molecular function term.
PSEPK	cheZ	IPR007439	GO:0009288	bacterial-type flagellum	MARK_AS_OVER_ANNOTATED	yes		This located_in annotation comes from an InterPro2GO mapping that conflates chemotaxis with the flagellar apparatus. CheZ is a soluble cytoplasmic enzyme that modulates the chemotaxis response regulator CheY; it is not a structural part of the bacterial-type flagellum and does not localize to the flagellar structure. The functional connection to motility is captured better by the chemotaxis process terms, and localization is already correctly represented by the cytoplasm annotation.
PSEPK	cheZ	IPR007439	GO:0050920	regulation of chemotaxis	ACCEPT	no		This is the core biological role of CheZ. By accelerating CheY-P dephosphorylation it controls the level of the chemotaxis output signal and thereby regulates chemotactic behavior. Supported by the conserved CheZ-family function and the UniProt FUNCTION annotation; the InterPro-based IEA is appropriate.
PSEPK	chrR	IPR005025	GO:0016491	oxidoreductase activity	MARK_AS_OVER_ANNOTATED	yes		Prefer the specific activity terms.
PSEPK	clpB	IPR001270,IPR002078,IPR003959,IPR018368	GO:0005524	ATP binding	MARK_AS_OVER_ANNOTATED	yes		ClpB is an AAA+ ATPase with two Walker-A (P-loop) nucleotide-binding sites, so ATP binding is correct. However, the more informative and specific molecular function 'ATP hydrolysis activity' (GO:0016887) is also annotated; ATP binding is a broad parent that adds little on its own and should be marked as over-annotated in favor of the catalytic term.
PSEPK	clpB	IPR002078	GO:0006355	regulation of DNA-templated transcription	REMOVE	yes		This annotation is incorrect. It derives from an InterPro match to IPR002078 (sigma-54 interaction domain), which reflects only the shared AAA+ ATPase fold between ClpB and sigma-54-dependent transcriptional activators (e.g. NtrC), not a genuine transcriptional function. ClpB is a protein disaggregase with no DNA-binding or transcriptional regulatory role and should not carry this term.
PSEPK	clpB	IPR017730	GO:0042026	protein refolding	ACCEPT	no		Correct and a core biological process. ClpB drives solubilization of aggregated proteins and, in cooperation with DnaK, their refolding to the native state. This disaggregation/refolding activity is the defining function of ClpB.
PSEPK	clpS	IPR003769	GO:0030163	protein catabolic process	ACCEPT	no		UniProt describes ClpS as modulating ClpAP-mediated ATP-dependent protein degradation, and falcon deep research confirms ClpS delivers N-degron substrates to the ClpAP protease for ATP-dependent degradation, placing the gene in the protein catabolic process / N-end rule pathway.
PSEPK	clpX	IPR010603	GO:0008270	zinc ion binding	ACCEPT	no		The C4-type zinc finger with four cysteine zinc ligands is a defining, conserved feature of ClpX and is a genuine molecular function.
PSEPK	clpX	IPR010603	GO:0046983	protein dimerization activity	MARK_AS_OVER_ANNOTATED	yes		ClpX forms a homohexamer rather than a dimer; the dimerization term is an over-annotation derived from a generic InterPro signature and does not represent a core function.
PSEPK	clpX	IPR004487	GO:0140662	ATP-dependent protein folding chaperone	ACCEPT	no		"Best available active MF term for the ATP-dependent unfoldase/chaperone activity of ClpX; the stand-alone chaperone function is documented in UniProt. PANTHER subfamily PTHR48102:SF7 (the ClpX-like ATP-binding subunit subfamily) corroborates that this protein is the ClpX AAA+ unfoldase, despite the eukaryote-derived "", MITOCHONDRIAL"" naming tag on the subfamily."
PSEPK	cobT	IPR017846	GO:0009236	cobalamin biosynthetic process	ACCEPT	no		CobT catalyzes alpha-ribazole biosynthesis, a lower-ligand step feeding cobalamin biosynthesis. I checked the more specific alpha-ribazole biosynthetic process term GO:0097290; it is obsolete and its consider terms include GO:0009236 and GO:0043755, where GO:0043755 is the CobC alpha-ribazole phosphatase molecular function, not CobT. Therefore GO:0009236 remains the appropriate current BP annotation.
PSEPK	colR	IPR001789,IPR001867	GO:0000160	phosphorelay signal transduction system	ACCEPT	no		This is the correct process-level annotation for ColR's place in the ColRS pathway.
PSEPK	crcB	IPR003691	GO:0016020	membrane	MARK_AS_OVER_ANNOTATED	yes		GO:0005886 captures the relevant localization with the needed specificity. The generic membrane term adds little value once plasma membrane is retained.
PSEPK	dinB	IPR017961,IPR036775	GO:0003684	damaged DNA binding	ACCEPT	no		Damaged DNA binding accurately reflects the lesion-bypass role of Pol IV and is consistent with its UmuC/DinB Y-family domain architecture.
PSEPK	dnaJ	IPR012724	GO:0005524	ATP binding	REMOVE	yes		DnaJ has no ATP-binding site or Walker motif in its sequence; ATP binding and hydrolysis are properties of its partner DnaK, so this is an erroneous family-level InterPro2GO transfer.
PSEPK	dnaJ	IPR008971,IPR012724	GO:0006457	protein folding	ACCEPT	no		Protein folding is a direct, core biological process for this J-domain co-chaperone of the DnaK folding cycle.
PSEPK	dnaJ	IPR012724	GO:0009408	response to heat	ACCEPT	no		DnaJ is a core component of the DnaK/DnaJ/GrpE heat-shock machinery that prevents and reverses heat-induced protein aggregation.
PSEPK	dnaJ	IPR001305	GO:0031072	heat shock protein binding	MODIFY	yes	GO:0051087 protein-folding chaperone binding	The interaction is real but 'heat shock protein binding' is imprecise; 'protein-folding chaperone binding' specifically captures the defining DnaK (Hsp70) co-chaperone interaction that DnaJ stimulates.
PSEPK	dnaJ		GO:0001671	ATPase activator activity	NEW	no		ATPase activator activity is the defining, most informative molecular function of this J-domain co-chaperone and is missing from the current GOA.
PSEPK	dnaK	IPR012725	GO:0006457	protein folding	ACCEPT	no		Core biological process for DnaK, well supported by family function and conserved domain architecture. Appropriately captured by an IEA annotation.
PSEPK	dnaK	IPR013126	GO:0016887	ATP hydrolysis activity	ACCEPT	no		Core molecular function of DnaK that powers the chaperone cycle. Strongly supported by family membership and conserved catalytic NBD; the IEA annotation is appropriate.
PSEPK	dnaK		GO:0051082	unfolded protein binding	NEW	no		Core molecular function of DnaK as an Hsp70 chaperone, capturing the direct binding of unfolded/non-native client proteins by the substrate-binding domain. Supported by family membership, the conserved peptide-binding domain, and the InterPro2GO mapping in UniProt; complements the protein folding (BP) annotation.
PSEPK	earP	IPR016633	GO:0106361	protein-arginine rhamnosyltransferase activity	ACCEPT	no		Retain as the precise molecular function.
PSEPK	eda	IPR000887	GO:0016829	lyase activity	MARK_AS_OVER_ANNOTATED	yes		The specific child term GO:0008675 already captures the evolved aldolase (lyase) activity, so the generic parent lyase term is a redundant high-level IEA over-annotation that should not be propagated as a distinct function.
PSEPK	edd	IPR020558	GO:0003824	catalytic activity	MARK_AS_OVER_ANNOTATED	yes		GO:0003824 is fully subsumed by GO:0004456 for this gene product and is therefore not informative as a separate functional statement.
PSEPK	exbB	IPR014164	GO:0022857	transmembrane transporter activity	MODIFY	yes	GO:0015078 proton transmembrane transporter activity	ExbB is a PMF-coupled energizer/proton channel, not a substrate-specific transmembrane transporter; the InterPro-derived generic term should be replaced with the proton-channel molecular function.
PSEPK	exbB	IPR014164	GO:0055085	transmembrane transport	MODIFY	yes	GO:1902600 proton transmembrane transport	The generic transmembrane transport term should be specialized to the proton movement that ExbB actually mediates.
PSEPK	fadB	IPR018376	GO:0003824	catalytic activity	MARK_AS_OVER_ANNOTATED	yes		Retain the specific FadB enzymatic activities instead.
PSEPK	fadB	IPR006108,IPR006176,IPR006180	GO:0006631	fatty acid metabolic process	MARK_AS_OVER_ANNOTATED	yes		Retain GO:0006635 and GO:0009062 for the reviewed process context.
PSEPK	fadB	IPR012799	GO:0009062	fatty acid catabolic process	ACCEPT	no		Retain the catabolic process annotation.
PSEPK	fadB	IPR006108,IPR006180	GO:0016491	oxidoreductase activity	MARK_AS_OVER_ANNOTATED	yes		Retain GO:0003857 and GO:0016509 instead.
PSEPK	fadB	IPR006108,IPR006180	GO:0016616	oxidoreductase activity, acting on the CH-OH group of donors, NAD or NADP as acceptor	MARK_AS_OVER_ANNOTATED	yes		Retain the specific dehydrogenase terms.
PSEPK	fadB	IPR012799	GO:0036125	fatty acid beta-oxidation multienzyme complex	ACCEPT	no		Retain the complex annotation.
PSEPK	fadB	IPR006176	GO:0070403	NAD+ binding	KEEP_AS_NON_CORE	yes		Retain as non-core cofactor binding.
PSEPK	fbp	IPR000146	GO:0005975	carbohydrate metabolic process	MARK_AS_OVER_ANNOTATED	yes		This is a correct but very broad parent of the specific gluconeogenesis process already captured, so it does not add informative content.
PSEPK	fbp	IPR000146	GO:0016791	phosphatase activity	MARK_AS_OVER_ANNOTATED	yes		The specific term GO:0042132 already captures the catalytic activity, making this generic parent a redundant high-level over-annotation.
PSEPK	ffh	IPR000897,IPR004125,IPR004780,IPR013822,IPR022941,IPR036891	GO:0006614	SRP-dependent cotranslational protein targeting to membrane	ACCEPT	no		Core biological process. This term precisely captures Ffh's role, co-translational recognition of the nascent-chain signal sequence and SRP/FtsY-mediated delivery to the membrane translocase. Strongly supported by the SRP family assignment (TIGR00959 ffh, IPR004780 SRP, PANTHER PTHR11564) and the UniProt function statement.
PSEPK	ffh	IPR004125,IPR036891	GO:0008312	7S RNA binding	ACCEPT	no		Core molecular function. The M domain of Ffh binds the SRP RNA (the bacterial 4.5S RNA, homologous to the eukaryotic 7S/SRP RNA) to form the SRP ribonucleoprotein. Supported by the SRP54 M-domain InterPro signatures (IPR004125, IPR036891) and the UniProt subunit/domain annotation.
PSEPK	fleQ	IPR002078	GO:0005524	ATP binding	ACCEPT	no		Although generic, ATP binding is part of the core mechanism of a sigma-54 bacterial enhancer-binding protein rather than an incidental property.
PSEPK	fleQ	IPR002078	GO:0006355	regulation of DNA-templated transcription	KEEP_AS_NON_CORE	yes		FleQ clearly regulates transcription, but this term is too unspecific to represent the biologically informative functions of the protein.
PSEPK	fleQ	IPR002197	GO:0043565	sequence-specific DNA binding	ACCEPT	no		Direct DNA-binding evidence exists in KT2440 for multiple named targets, and this function underlies both the motility and biofilm branches of FleQ regulation.
PSEPK	flgK	IPR002371	GO:0005198	structural molecule activity	ACCEPT	no		Structural molecule activity is the best current MF term for this flagellar junction component.
PSEPK	flgK	IPR002371	GO:0009424	bacterial-type flagellum hook	MODIFY	yes	GO:0009422 bacterial-type flagellum hook-filament junction	Use GO:0009422 because it names the hook-filament junction, whereas GO:0009424 describes the hook proper.
PSEPK	flgL	IPR001029,IPR001492	GO:0005198	structural molecule activity	ACCEPT	no		Structural molecule activity is the best current MF term for a hook-associated flagellar protein. Falcon deep research confirms FlgL is a structural adaptor/mechanical element rather than an enzyme or transporter.
PSEPK	flgL	IPR013384	GO:0009424	bacterial-type flagellum hook	MODIFY	yes	GO:0009422 bacterial-type flagellum hook-filament junction	Use GO:0009422 because it names the hook-filament junction, whereas GO:0009424 describes the hook proper. Falcon deep research, citing a 2.9 Angstrom cryo-EM structure, shows FlgL assembles as the distal layer of the hook-filament junction linking the FlgE hook to the FliC filament - not as a component of the hook itself - directly supporting this refinement.
PSEPK	flgL	IPR013384	GO:0071973	bacterial-type flagellum-dependent cell motility	ACCEPT	no		Motility is the direct biological context for this structural flagellar component. Falcon deep research confirms that disrupting the FlgK-FlgL junction reduces swimming motility and filament retention.
PSEPK	flgM	IPR007412	GO:0045892	negative regulation of DNA-templated transcription	ACCEPT	no		Negative regulation of DNA-templated transcription captures the direct anti-sigma regulatory effect.
PSEPK	fliA	IPR000943,IPR007624,IPR007627,IPR007630,IPR013325,IPR014284	GO:0003700	DNA-binding transcription factor activity	MODIFY	yes	GO:0016987 sigma factor activity	Replace the broad transcription-factor term with the specific sigma factor molecular function.
PSEPK	fliA	IPR012845,IPR028617	GO:0003899	DNA-directed RNA polymerase activity	REMOVE	yes		RNA polymerase catalytic activity belongs to the core polymerase complex, whereas FliA provides promoter specificity.
PSEPK	fliG	IPR000090	GO:0003774	cytoskeletal motor activity	ACCEPT	no		Term definition explicitly covers flagellar-rotation torque generation, and FliG is the rotor/torque-transmitting switch protein. Consistent with conserved FliG mechanism (PMID:31452860). Core molecular function.
PSEPK	fliG	IPR000090	GO:0006935	chemotaxis	KEEP_AS_NON_CORE	yes		FliG mediates the motor-switching output of chemotaxis (CheY-P -> C-ring -> FliG reorientation), but its core process is flagellar rotation/motility; chemotaxis is the higher-level process it serves.
PSEPK	fliG	IPR000090	GO:0009288	bacterial-type flagellum	ACCEPT	no		FliG is a bona fide flagellar structural protein; accurate location.
PSEPK	fpvA	IPR010105	GO:0015343	siderophore-iron transmembrane transporter activity	ACCEPT	no		This term accurately describes the activity of a TonB-dependent ferri-siderophore receptor that imports the iron-loaded siderophore complex. Well supported by family/domain evidence (TonB-dependent siderophore receptor, IPR010105) and by the gene's identity as the ferripyoverdine receptor.
PSEPK	fpvA	IPR010105	GO:0015891	siderophore transport	ACCEPT	no		Directly supported by gene identity as ferripyoverdine receptor and TonB-dependent siderophore receptor domain evidence.
PSEPK	fpvA	IPR011662	GO:0019867	outer membrane	KEEP_AS_NON_CORE	yes		Not wrong, but GO:0009279 (cell outer membrane) is the preferred, more specific term for a Gram-negative bacterial outer membrane protein and is already present. Retained as a redundant parent rather than removed.
PSEPK	fpvA	IPR010105	GO:0038023	signaling receptor activity	KEEP_AS_NON_CORE	yes		Cell-surface signaling is a plausible and domain-supported secondary function, but it is an IEA inference based on the STN domain and is not the receptor's core function (transport). There is no direct KT2440-specific experimental evidence that FpvA transduces a signal. Retained as a non-core, domain-inferred activity rather than removed.
PSEPK	ftsY	IPR000897,IPR004390,IPR013822	GO:0006614	SRP-dependent cotranslational protein targeting to membrane	ACCEPT	no		This annotation precisely describes the core biological process in which FtsY participates. FtsY is the bacterial SRP receptor that, together with SRP (Ffh + 4.5S RNA), mediates co-translational targeting of nascent membrane and secretory proteins to the SecYEG translocon. This is the primary and defining function of FtsY across bacteria.
PSEPK	fumC	IPR008948,IPR020557	GO:0003824	catalytic activity	MARK_AS_OVER_ANNOTATED	yes		GO:0003824 is a high-level grouping term. The more specific GO:0004333 (fumarate hydratase activity) is annotated and fully captures the molecular function, making this generic term redundant and uninformative.
PSEPK	gacA	IPR039420	GO:0000976	transcription cis-regulatory region binding	KEEP_AS_NON_CORE	yes		The term is informative and consistent with the HTH LuxR-type output domain, but direct cis-regulatory-region binding has been demonstrated only in other pseudomonads, not in KT2440, so it is retained as non-core rather than as a core function.
PSEPK	gacA	IPR016032	GO:0003677	DNA binding	MODIFY	yes	GO:0000156 phosphorelay response regulator activity; GO:0003700 DNA-binding transcription factor activity	The annotation is correct in essence but overly general compared with more specific terms already supported by domain architecture and literature synthesis.
PSEPK	gacA	IPR001789	GO:0000160	phosphorelay signal transduction system	ACCEPT	no		This is the central biological-process annotation for GacA and is directly aligned with both sequence architecture and experimental interpretation in KT2440 studies.
PSEPK	gacA	IPR000792,IPR016032,IPR039420	GO:0006355	regulation of DNA-templated transcription	MODIFY	yes	GO:0045893 positive regulation of DNA-templated transcription	The annotation is correct in essence but unsigned; falcon synthesis shows GacA is specifically a transcriptional activator (master activator of sRNA genes), so the more informative GO:0045893 positive regulation of DNA-templated transcription is preferred over the generic regulation term.
PSEPK	gacS	IPR004358	GO:0016772	transferase activity, transferring phosphorus-containing groups	MARK_AS_OVER_ANNOTATED	yes		The term is correct only at a very high level and should not be treated as a core annotation for a well-characterized hybrid sensor kinase.
PSEPK	gacS	IPR001789,IPR008207,IPR036641	GO:0000160	phosphorelay signal transduction system	ACCEPT	no		GacS is a membrane hybrid sensor kinase whose core biological role is initiating phosphorelay signaling, with adhesion and secretion phenotypes representing downstream outputs of that regulatory cascade.
PSEPK	gacS	IPR003660,IPR003661,IPR036097	GO:0007165	signal transduction	MARK_AS_OVER_ANNOTATED	yes		The more specific phosphorelay term should carry the biology here; the generic parent adds little value.
PSEPK	gacS	IPR003660	GO:0016020	membrane	MARK_AS_OVER_ANNOTATED	yes		GO:0005886 plasma membrane is the more informative and appropriate cellular-component annotation for GacS.
PSEPK	galA	IPR004183	GO:0008198	ferrous iron binding	KEEP_AS_NON_CORE	yes		GalA uses Fe(2+) as cofactor, but its core molecular function is gallate dioxygenase activity.
PSEPK	galA	IPR004183	GO:0016491	oxidoreductase activity	MARK_AS_OVER_ANNOTATED	yes		The exact gallate dioxygenase term should be used instead of this broad oxidoreductase parent.
PSEPK	galP	IPR005318	GO:0016020	membrane	MODIFY	yes	GO:0009279 cell outer membrane	GalP belongs to the outer membrane porin family; GO:0009279 is more specific than generic membrane for a Gram-negative bacterial porin.
PSEPK	galR	IPR000847	GO:0003700	DNA-binding transcription factor activity	MODIFY	yes	GO:0001216 DNA-binding transcription activator activity	UniProt and InterPro support the HTH LysR-type regulator assignment, and the parent term is correct. However, the 2023 functional study shows GalR positively regulates (activates) the gal cluster promoters, supporting the more informative child GO:0001216 (DNA-binding transcription activator activity).
PSEPK	gapA	IPR006424	GO:0006006	glucose metabolic process	ACCEPT	no		Family/domain-based IEA annotation consistent with the well-established role of GAPDH in glucose metabolism; supported by P. putida pathway literature.
PSEPK	gapA	IPR006424,IPR020829,IPR020830,IPR020831	GO:0016620	oxidoreductase activity, acting on the aldehyde or oxo group of donors, NAD or NADP as acceptor	MODIFY	yes	GO:0004365 glyceraldehyde-3-phosphate dehydrogenase (NAD+) (phosphorylating) activity	The term is correct but too general. The protein is a canonical phosphorylating, NAD-dependent GAPDH (TIGR01534 GAPDH-I, PROSITE PS00071, with catalytic Cys at position 154 and bound NAD+), so the specific child term is warranted.
PSEPK	gapA	IPR006424	GO:0050661	NADP binding	REMOVE	yes		Over-propagated electronic inference from a generic NAD(P)-binding domain signature. The structural evidence (NAD+-only binding sites) and GAPDH-I family membership argue against NADP binding for this specific protein. NAD binding is already captured separately.
PSEPK	gapA	IPR006424,IPR020828	GO:0051287	NAD binding	ACCEPT	no		Strongly supported by domain architecture and conserved NAD+-binding residues; consistent with NAD-dependent GAPDH-I family membership.
PSEPK	gcd	IPR017511	GO:0016020	membrane	MODIFY	yes	GO:0005887 integral component of plasma membrane	The generic membrane term fails to capture that Gcd is specifically an integral inner membrane protein with multiple transmembrane helices. UniProt features show 5 predicted TM helices and the protein is classified as a membrane-bound PQQ dehydrogenase (IPR017511, PQQ_mDH). GO:0005887 captures both the specific membrane identity and the integral nature of the association.
PSEPK	gcd	IPR017511	GO:0016614	oxidoreductase activity, acting on CH-OH group of donors	KEEP_AS_NON_CORE	yes		Redundant with the more specific GO:0008876 already annotated. The InterPro2GO mapping from IPR017511 generates this term automatically. While not wrong, the specific term GO:0008876 is more informative and already present.
PSEPK	gcd	IPR017511	GO:0048038	quinone binding	MODIFY	yes	GO:0070968 pyrroloquinoline quinone binding	GO:0070968 (pyrroloquinoline quinone binding) is a more specific and accurate child term of GO:0048038 that precisely describes the cofactor binding of Gcd. UniProt annotates PQQ as cofactor, the protein belongs to the bacterial PQQ dehydrogenase family, and the PQQ repeat domain is the primary structural feature.
PSEPK	gdhA	IPR006095,IPR006096,IPR006097	GO:0006520	amino acid metabolic process	KEEP_AS_NON_CORE	yes		Correct but general biological process. GDH interconverts L-glutamate and 2-oxoglutarate, participating in glutamate (amino-acid) metabolism. The InterPro-derived term is broader than the specific glutamate biosynthetic/catabolic role; kept as a supporting non-core process term.
PSEPK	gdhA	IPR006095,IPR006096,IPR006097	GO:0016491	oxidoreductase activity	MARK_AS_OVER_ANNOTATED	yes		Very general oxidoreductase root-level term derived from InterPro signatures. GDH is an oxidoreductase, but this term is uninformative relative to the specific EC 1.4.1.4 activity already captured by GO:0004354.
PSEPK	gdhA	IPR014362,IPR033922	GO:0016639	oxidoreductase activity, acting on the CH-NH2 group of donors, NAD or NADP as acceptor	KEEP_AS_NON_CORE	yes		A more specific parent describing the chemistry (oxidation of the L-glutamate CH-NH2/amino group with NAD(P) as electron acceptor), derived from InterPro IPR014362/IPR033922 (Glu_DH). Correct but a generalization of the precise glutamate dehydrogenase (NADP+) activity; kept as a non-core supporting term.
PSEPK	glaH	IPR015038	GO:0005506	iron ion binding	MARK_AS_OVER_ANNOTATED	yes		True but generic; the more specific ferrous iron binding term is present and preferred.
PSEPK	glk	IPR003836	GO:0005536	D-glucose binding	MARK_AS_OVER_ANNOTATED	yes		This binding term adds little beyond the core enzymatic activity term.
PSEPK	glk	IPR003836	GO:0051156	glucose 6-phosphate metabolic process	ACCEPT	no		Directly describes the metabolic process in which the enzymatic reaction participates.
PSEPK	glnA	IPR014746	GO:0003824	catalytic activity	MARK_AS_OVER_ANNOTATED	yes		Root-level catalytic activity term derived from an InterPro signature (IPR014746, Gln_synth/guanido_kin catalytic domain). It is correct but entirely uninformative relative to the specific glutamine synthetase activity (GO:0004356, EC 6.3.1.2) already annotated.
PSEPK	glpK	IPR000577,IPR018483,IPR018484,IPR018485	GO:0005975	carbohydrate metabolic process	MARK_AS_OVER_ANNOTATED	yes		Broad parent biological-process term from the FGGY carbohydrate kinase InterPro signature (IPR000577). It is correct in the general sense but far less informative than the specific glycerol catabolic process (GO:0019563) and glycerol metabolic process (GO:0006071) also annotated. Marking as over-annotated.
PSEPK	glpK	IPR005999	GO:0006072	glycerol-3-phosphate metabolic process	KEEP_AS_NON_CORE	yes		Glycerol kinase produces sn-glycerol 3-phosphate, so participation in glycerol-3-phosphate metabolism is accurate (InterPro IPR005999). This is a reasonable supporting process term, kept as non-core relative to the primary glycerol catabolic process.
PSEPK	glpK	IPR018483	GO:0016773	phosphotransferase activity, alcohol group as acceptor	KEEP_AS_NON_CORE	yes		Accurate parent term describing the reaction class (phosphate transferred to the C3 alcohol group of glycerol; InterPro IPR018483). More general than the specific glycerol kinase activity (GO:0004370). Keeping as non-core.
PSEPK	gltA	IPR002020,IPR019810,IPR024176,IPR036969	GO:0046912	acyltransferase activity, acyl groups converted into alkyl on transfer	MARK_AS_OVER_ANNOTATED	yes		Redundant, less-specific ancestor of the already-annotated specific function GO:0036440; provides no additional information about gltA function.
PSEPK	gltB	IPR002932	GO:0016638	oxidoreductase activity, acting on the CH-NH2 group of donors	KEEP_AS_NON_CORE	yes		A more specific parent describing the chemistry (oxidation of the CH-NH2/amino group during glutamate formation), derived from InterPro IPR002932. Correct but a generalization of the precise glutamate synthase (NADPH) activity; kept as non-core supporting term.
PSEPK	gltD	IPR023753	GO:0016491	oxidoreductase activity	MARK_AS_OVER_ANNOTATED	yes		Very general oxidoreductase term derived from the FAD/NAD-binding InterPro signature (IPR023753). Correct in that GltD is the flavin/NAD(P)-dependent oxidoreductase subunit, but uninformative relative to the specific glutamate synthase (NADPH) activity already annotated.
PSEPK	gltD	IPR009051	GO:0051536	iron-sulfur cluster binding	KEEP_AS_NON_CORE	yes		Parent term for iron-sulfur cluster binding (InterPro IPR009051, helical ferredoxin). Correct but more general than the specific [4Fe-4S] cluster binding term also annotated; kept as non-core to avoid redundancy.
PSEPK	gltD	IPR006006	GO:0051539	4 iron, 4 sulfur cluster binding	ACCEPT	no		Supporting molecular function. GltD binds a [4Fe-4S] cluster (UniProt COFACTOR; 4Fe-4S ferredoxin-type domain PROSITE PS51379, InterPro IPR006006/IPR017896) that mediates electron transfer to the catalytic large chain. Accept as a well-supported cofactor-binding function.
PSEPK	gmhB	IPR004446	GO:0005975	carbohydrate metabolic process	MARK_AS_OVER_ANNOTATED	yes		The ADP-L-glycero-beta-D-manno-heptose biosynthetic process annotation is more specific.
PSEPK	gmhB	IPR004446,IPR006543	GO:0016791	phosphatase activity	MARK_AS_OVER_ANNOTATED	yes		GO:0034200 captures the substrate and reaction position and should be used for core function.
PSEPK	gpsA	IPR006109	GO:0005975	carbohydrate metabolic process	MODIFY	yes	GO:0046474 glycerophospholipid biosynthetic process	The enzyme reduces DHAP to glycerol-3-phosphate to feed phospholipid synthesis, not carbohydrate metabolism; replace with the specific glycerophospholipid biosynthetic process term.
PSEPK	gpsA	IPR011128	GO:0016616	oxidoreductase activity, acting on the CH-OH group of donors, NAD or NADP as acceptor	MARK_AS_OVER_ANNOTATED	yes		The specific activity term GO:0047952 is present and captures the function more precisely; the general oxidoreductase class adds no information.
PSEPK	gpsA	IPR011128	GO:0046168	glycerol-3-phosphate catabolic process	REMOVE	yes		"The biosynthetic GpsA produces rather than degrades glycerol-3-phosphate; the catabolic annotation is the wrong direction for this gene. PANTHER classifies gpsA in the biosynthetic NAD(P)+ glycerol-3-phosphate dehydrogenase family/subfamily (PTHR11728 / PTHR11728:SF1), despite the eukaryote-biased "", CHLOROPLASTIC"" subfamily naming artifact, reinforcing the G3P-producing rather than G3P-catabolizing assignment."
PSEPK	gpsA	IPR011128	GO:0051287	NAD binding	MARK_AS_OVER_ANNOTATED	yes		Cofactor binding is implied by the specific dehydrogenase activity; the generic NAD binding term adds little and omits the NADP specificity of this enzyme.
PSEPK	groEL	IPR018370	GO:0006457	protein folding	ACCEPT	no		Directly captures the central biological role of the chaperonin and is consistent with the UniProt FUNCTION annotation and extensive literature.
PSEPK	groEL	IPR001844	GO:0140662	ATP-dependent protein folding chaperone	ACCEPT	no		This is the most precise molecular function term for GroEL and is strongly supported; it represents a core function of the gene.
PSEPK	groES	IPR018369,IPR020818	GO:0005524	ATP binding	REMOVE	yes		This InterPro-based IEA annotation conflates the ATP-dependent GroEL/GroES cycle with intrinsic ATP binding by GroES. GroES does not bind ATP; ATP binding is performed by the GroEL subunit. The annotation is an over-propagation from a family-level signature and is not appropriate for the co-chaperonin.
PSEPK	groES	IPR020818	GO:0044183	protein folding chaperone	ACCEPT	no		GroES acts as a co-chaperonin that, in cooperation with GroEL, mediates protein folding. This molecular-function term captures the chaperone activity and is a core function annotation.
PSEPK	grpE	IPR000740,IPR009012	GO:0006457	protein folding	ACCEPT	no		Accurately captures the biological process in which GrpE participates. GrpE is not itself a foldase but is essential to the folding cycle of the KJE system.
PSEPK	grpE	IPR000740	GO:0042803	protein homodimerization activity	ACCEPT	no		GrpE is obligately dimeric and dimerization is required for function. Correct molecular function annotation.
PSEPK	grpE	IPR000740	GO:0051087	protein-folding chaperone binding	ACCEPT	no		GrpE's physical interaction with the DnaK chaperone is central to its function. The term correctly describes this binding to a folding chaperone rather than an uninformative generic protein binding term.
PSEPK	gyrA	IPR006691	GO:0003916	DNA topoisomerase activity	KEEP_AS_NON_CORE	yes		General topoisomerase activity term assigned by InterPro2GO from the GyrA/ParC repeat signature (IPR006691). It is correct but a broad parent of the specific type II (GO:0003918) and negative supercoiling (GO:0034335) activities also annotated. Kept as non-core in favor of the precise terms.
PSEPK	gyrA	IPR005743	GO:0005694	chromosome	ACCEPT	no		Gyrase acts on the bacterial chromosome and is associated with chromosomal DNA; the InterPro2GO mapping from the GyrA signature (IPR005743) is consistent with its substrate. Accept as a supporting cellular component.
PSEPK	gyrA	IPR013758	GO:0006259	DNA metabolic process	MARK_AS_OVER_ANNOTATED	yes		Broad parent biological process term assigned by InterPro2GO (IPR013758). Correct but far less informative than the specific GO:0006265 (DNA topological change) also annotated. Marking as over-annotated relative to the precise child term.
PSEPK	gyrB	IPR011557	GO:0005694	chromosome	ACCEPT	no		Gyrase acts on the bacterial chromosome and is associated with chromosomal DNA; the InterPro2GO mapping is consistent with its substrate. Accept as a supporting cellular component.
PSEPK	hexR	IPR047640	GO:0003677	DNA binding	MARK_AS_OVER_ANNOTATED	yes		True but uninformative; more specific child terms (transcription cis-regulatory region binding and DNA-binding transcription repressor activity) are present and better describe the function.
PSEPK	hexR	IPR001347,IPR046348,IPR047640	GO:0097367	carbohydrate derivative binding	KEEP_AS_NON_CORE	yes		Correct and biologically meaningful as it reflects effector (KDPG) binding by the SIS domain, but broad and not the core repressor function.
PSEPK	hexR	IPR001347,IPR046348	GO:1901135	carbohydrate derivative metabolic process	MARK_AS_OVER_ANNOTATED	yes		HexR does not itself carry out carbohydrate-derivative metabolism; it is a transcriptional regulator. The term is an InterPro SIS-domain over-call. PANTHER places HexR in the HexR-repressor subfamily (PTHR30514:SF1), a transcriptional regulator, not a carbohydrate-metabolizing enzyme.
PSEPK	hfq	IPR005001	GO:0006355	regulation of DNA-templated transcription	MODIFY	yes	GO:0045974 regulation of translation, ncRNA-mediated	Hfq does not bind DNA or directly regulate transcription initiation/elongation; its regulatory role is post-transcriptional (sRNA-mediated effects on translation and RNA stability). The more accurate term is ncRNA-mediated regulation of translation, which is already separately annotated. This generic transcription-regulation term is an over-broad/incorrect propagation and should be replaced.
PSEPK	hisC	IPR001917	GO:0016740	transferase activity	MARK_AS_OVER_ANNOTATED	yes		Redundant generic ancestor of GO:0004400; adds no information beyond the specific transaminase MF term.
PSEPK	hisC	IPR004839	GO:0030170	pyridoxal phosphate binding	ACCEPT	no		PLP binding is an essential, well-supported molecular function of this enzyme. The PLP-lysine internal aldimine and ping-pong mechanism are documented for HisC homologs (see hisC-deep-research-falcon.md).
PSEPK	hisD	IPR016161	GO:0016491	oxidoreductase activity	MARK_AS_OVER_ANNOTATED	yes		Correct but very general parent term for the dehydrogenase chemistry. The specific histidinol dehydrogenase activity (GO:0004399) is already captured; mark this root-level term as over-annotated.
PSEPK	hisD	IPR001692,IPR012131	GO:0016616	oxidoreductase activity, acting on the CH-OH group of donors, NAD or NADP as acceptor	KEEP_AS_NON_CORE	yes		Correct intermediate-level parent describing the CH-OH/NAD oxidoreductase chemistry of HisD. Less informative than the specific EC 1.1.1.23 term; keep as non-core.
PSEPK	hisD	IPR012131,IPR022695	GO:0046872	metal ion binding	KEEP_AS_NON_CORE	yes		Correct but general parent of the specific zinc ion binding (GO:0008270) already annotated. Keep as non-core.
PSEPK	hisD	IPR012131,IPR022695	GO:0051287	NAD binding	KEEP_AS_NON_CORE	yes		Correct supporting molecular function. HisD uses NAD+ as the electron acceptor (2 NAD+ per L-histidinol oxidized). Accept; underpins the core dehydrogenase activity, kept as supporting.
PSEPK	hmp	IPR001433,IPR017927	GO:0016491	oxidoreductase activity	MARK_AS_OVER_ANNOTATED	yes		Generic oxidoreductase parent; the specific NOD activity term is present and preferred.
PSEPK	hmp	IPR012292,IPR023950	GO:0019825	oxygen binding	MARK_AS_OVER_ANNOTATED	yes		Generic molecular function describing a substrate-binding property already captured by the specific nitric oxide dioxygenase activity.
PSEPK	hmp	IPR000971,IPR012292,IPR023950	GO:0020037	heme binding	MARK_AS_OVER_ANNOTATED	yes		True cofactor-binding term but generic; the specific NOD activity is the core function.
PSEPK	hpd	IPR005956	GO:0009072	aromatic amino acid metabolic process	MODIFY	yes	GO:0009074 aromatic amino acid catabolic process	The annotation is correct but the generic metabolic term under-specifies the function. Replace with the catabolic process term, which captures the documented degradative role.
PSEPK	hpd	IPR005956	GO:0016701	oxidoreductase activity, acting on single donors with incorporation of molecular oxygen	MARK_AS_OVER_ANNOTATED	yes		Grouping/parent term subsumed by the specific GO:0003868 annotation; retained for completeness but adds no specific functional information.
PSEPK	htpG	IPR001404	GO:0016887	ATP hydrolysis activity	ACCEPT	no		ATPase activity is a defining catalytic feature of the Hsp90/HtpG family; UniProt also records ATPase activity for this protein.
PSEPK	htpG	IPR001404	GO:0140662	ATP-dependent protein folding chaperone	ACCEPT	no		The most specific and accurate molecular-function term for an Hsp90-family chaperone; well supported by conserved family biology.
PSEPK	hutT	IPR004840	GO:0006865	amino acid transport	MARK_AS_OVER_ANNOTATED	yes		Prefer the added L-histidine transport annotation for the reviewed biology. Competition assays establish narrow specificity for L-histidine, with little or no transport of other amino acids, so the generic amino acid transport term is an over-annotation.
PSEPK	hutT	IPR004840,IPR004841	GO:0016020	membrane	MARK_AS_OVER_ANNOTATED	yes		Retain GO:0005886 instead.
PSEPK	hutT	IPR004840,IPR004841	GO:0055085	transmembrane transport	ACCEPT	no		Retain the broad transport process because it is directly supported.
PSEPK	icd	IPR019818	GO:0000287	magnesium ion binding	ACCEPT	no		Consistent with the IDH/IMDH family requirement for a divalent metal cofactor; UniProt records both Mg2+ and Mn2+ cofactors and a Mg2+-binding site.
PSEPK	icd	IPR019818	GO:0016616	oxidoreductase activity, acting on the CH-OH group of donors, NAD or NADP as acceptor	MARK_AS_OVER_ANNOTATED	yes		Redundant grandparent of the specific MF term GO:0004450 that is already present; provides no additional specificity.
PSEPK	icd	IPR019818	GO:0051287	NAD binding	REMOVE	yes	GO:0050661 NADP binding	Contradicted by cofactor specificity. The enzyme binds NADP+, not NAD+; this is an over-propagated InterPro IEA inference. NADP binding (GO:0050661) would be the correct term.
PSEPK	ilvC	IPR000506,IPR013023,IPR014359	GO:0009082	branched-chain amino acid biosynthetic process	MARK_AS_OVER_ANNOTATED	yes		IlvC acts at a shared BCAA pathway step; the specific L-valine annotation and missing isoleucine annotation are more informative.
PSEPK	ilvC	IPR013023	GO:0016491	oxidoreductase activity	MARK_AS_OVER_ANNOTATED	yes		The specific EC-linked ketol-acid reductoisomerase annotation should be preferred over the broad oxidoreductase parent.
PSEPK	ilvC	IPR014359	GO:0050661	NADP binding	KEEP_AS_NON_CORE	yes		The reaction uses NADP/NADPH, but binding alone is less informative than the enzyme activity.
PSEPK	ispD	IPR018294	GO:0003824	catalytic activity	MARK_AS_OVER_ANNOTATED	yes		The specific MEP cytidylyltransferase term GO:0050518 captures the enzyme function.
PSEPK	ispD	IPR001228,IPR018294	GO:0008299	isoprenoid biosynthetic process	MARK_AS_OVER_ANNOTATED	yes		GO:0019288 (MEP-pathway IPP biosynthesis) is the precise process term and is the parent-replacing specific annotation; the broad GO:0008299 parent adds no information beyond it.
PSEPK	ispD	IPR034683	GO:0070567	cytidylyltransferase activity	MARK_AS_OVER_ANNOTATED	yes		The exact substrate-specific activity GO:0050518 should replace this broader parent where possible.
PSEPK	katA	IPR018028,IPR024711,IPR040333	GO:0006979	response to oxidative stress	KEEP_AS_NON_CORE	yes		KatA contributes to oxidative-stress survival, yet the more specific core process is hydrogen peroxide catabolism. This term is better treated as contextual rather than as the primary evolved function.
PSEPK	katG	IPR000763,IPR002016,IPR010255	GO:0006979	response to oxidative stress	ACCEPT	no		H2O2 decomposition by catalase-peroxidase is a principal mechanism of defense against oxidative stress, consistent with the bifunctional H2O2-detoxifying activity recorded in UniProt.
PSEPK	lapA	IPR001343	GO:0005509	calcium ion binding	KEEP_AS_NON_CORE	yes		The annotation is not wrong, but it under-describes LapA. Direct KT2440 studies emphasize LapA's role as the major surface adhesin required for stable attachment and biofilm development, while UniProt domain structure explains why InterPro infers calcium binding. Retaining the term as non-core preserves the mechanistic signal without letting it dominate the review.
PSEPK	lapD	IPR003660	GO:0007165	signal transduction	MODIFY	yes	GO:0045861 negative regulation of proteolysis; GO:1900189 positive regulation of cell adhesion involved in single-species biofilm formation	"The broad parent term ""signal transduction"" obscures the actual process controlled by LapD. A more informative representation is regulation of LapG-dependent proteolysis and positive regulation of adhesive/biofilm states driven by LapA retention at the cell surface."
PSEPK	lapD	IPR003660	GO:0016020	membrane	ACCEPT	no		Although generic, the term is accurate. LapD is unequivocally membrane associated, and membrane anchoring is essential for its inside-out signaling mechanism.
PSEPK	lexA2	IPR006197	GO:0006355	regulation of DNA-templated transcription	MARK_AS_OVER_ANNOTATED	yes		Retain GO:0045892 and GO:0001217 instead.
PSEPK	lexA2	IPR006199	GO:0006508	proteolysis	KEEP_AS_NON_CORE	yes		Retain as non-core process context for autocleavage.
PSEPK	lon	IPR004815,IPR008269,IPR027543	GO:0006508	proteolysis	KEEP_AS_NON_CORE	yes		Correct but general biological process. Lon degrades polypeptides processively into short peptides; proteolysis is the broad parent process. The more specific protein quality control and protein catabolic process terms below better capture the biological role, so this general term is kept as non-core.
PSEPK	lon	IPR027065	GO:0030163	protein catabolic process	ACCEPT	no		Accurate biological process. Lon catabolizes proteins, degrading both abnormal proteins and short-lived regulatory proteins. Accept; this together with protein quality control captures the in vivo role.
PSEPK	lysA	IPR000183,IPR009006,IPR022643,IPR022644	GO:0003824	catalytic activity	MARK_AS_OVER_ANNOTATED	yes		Root-level molecular function term assigned by InterPro2GO from generic decarboxylase signatures (IPR000183, IPR009006). It is correct but uninformative compared to the specific GO:0008836 (diaminopimelate decarboxylase activity) that is also annotated. Marking as over-annotated in favor of the precise EC 4.1.1.20 activity term.
PSEPK	mcpS	IPR004090	GO:0004888	transmembrane signaling receptor activity	ACCEPT	no		Retain as the molecular-function annotation available in GOA. This is the standard MF term for methyl-accepting chemotaxis proteins, which act as transmembrane chemosensory receptors. Falcon deep research independently confirms the transmembrane MCP receptor architecture.
PSEPK	mcpS	IPR003660,IPR004089,IPR004090	GO:0007165	signal transduction	KEEP_AS_NON_CORE	yes		Retain as a broad non-core process. Signal transduction is the generic parent of the chemotaxis signaling that McpS performs via the CheA/CheW/CheY cascade; the more specific chemotaxis annotation captures the core function.
PSEPK	mcpS	IPR003660,IPR004089,IPR004090	GO:0016020	membrane	MARK_AS_OVER_ANNOTATED	yes		Retain GO:0005886 instead.
PSEPK	mdh	IPR015955	GO:0003824	catalytic activity	KEEP_AS_NON_CORE	yes		The gene product is an enzyme so catalytic activity is true, but this is a very general parent of the specific malate dehydrogenase activity (GO:0030060) and carries no specific information. Retained as non-core.
PSEPK	mdh	IPR001236	GO:0016491	oxidoreductase activity	KEEP_AS_NON_CORE	yes		True but general parent of GO:0030060. Retained as non-core background.
PSEPK	mdh	IPR001557,IPR011275,IPR015955,IPR022383	GO:0016616	oxidoreductase activity, acting on the CH-OH group of donors, NAD or NADP as acceptor	KEEP_AS_NON_CORE	yes		Accurately describes the enzyme class (NAD-linked CH-OH oxidoreductase) but is a parent of the specific GO:0030060 L-malate dehydrogenase (NAD+) activity. Retained as non-core.
PSEPK	metE	IPR002629	GO:0003871	5-methyltetrahydropteroyltriglutamate-homocysteine S-methyltransferase activity	ACCEPT	no		Core molecular function. This is the EC 2.1.1.14 activity of cobalamin-independent methionine synthase (MetE), matching the UniProt protein name and InterPro signature. Strongly supported by the conserved MetE domain architecture; accept as the defining activity of the gene product.
PSEPK	metE	IPR002629	GO:0008270	zinc ion binding	ACCEPT	no		MetE is a zinc metalloenzyme; the catalytic zinc ion coordinates and activates the homocysteine thiol for methyl transfer. Accept as a supporting molecular function directly required for catalysis.
PSEPK	metE		GO:0009086	L-methionine biosynthetic process	NEW	no		Proposed new biological-process annotation. The current GOA lacks a BP term for metE, but cobalamin-independent methionine synthase catalyzes the committed terminal step of de novo L-methionine biosynthesis (5-methyltetrahydropteroyltriglutamate + L-homocysteine -> L-methionine + tetrahydropteroyltriglutamate; UniProt PATHWAY annotates L-methionine biosynthesis via de novo pathway, step 1/1). This BP is well supported by the EC 2.1.1.14 activity and the conserved MetE family assignment and should be added, mirroring the paired terminal-step biosynthetic enzymes lysA, proC, thrC, argG, and hisD that all carry the corresponding amino-acid biosynthetic-process term.
PSEPK	mexB	IPR004764	GO:0015562	efflux transmembrane transporter activity	ACCEPT	no		"Core molecular function. MexB-type RND proteins are the energized efflux transporter subunit that exports substrates outward across the membrane. Matches the UniProt ""Efflux pump membrane transporter"" name and RND family assignment. Accept."
PSEPK	mexB	IPR001036,IPR004764	GO:0016020	membrane	KEEP_AS_NON_CORE	yes		"Correct but general. ""Membrane"" is a broad parent of the plasma membrane localization already annotated. Keep as non-core in favor of the more specific GO:0005886."
PSEPK	mexB	IPR001036	GO:0022857	transmembrane transporter activity	KEEP_AS_NON_CORE	yes		Correct but general parent of the efflux transporter activity. Keep as non-core in favor of the more specific efflux/xenobiotic transporter terms.
PSEPK	mexB	IPR004764	GO:0042908	xenobiotic transport	ACCEPT	no		Core biological process. The pump exports structurally diverse xenobiotics (antibiotics, solvents, dyes) out of the cell. Accept as a defining biological role.
PSEPK	mexB	IPR001036	GO:0055085	transmembrane transport	KEEP_AS_NON_CORE	yes		Correct but general parent process of xenobiotic transport. Keep as non-core in favor of the more specific GO:0042908.
PSEPK	miaE	IPR010386	GO:0006400	tRNA modification	ACCEPT	no		The P. putida MiaE publication and UniProt entry establish MiaE as a tRNA-hydroxylase enzyme acting on position 37 of tRNA.
PSEPK	motA	IPR047055	GO:0006935	chemotaxis	MARK_AS_OVER_ANNOTATED	yes		Prefer bacterial-type flagellum-dependent cell motility and proton transmembrane transport for the direct stator role. The chemotaxis IEA derives from the UniProt Chemotaxis keyword, but MotA is a torque generator, not a chemoreceptor or signaling component.
PSEPK	mraY	IPR000715,IPR003524	GO:0016020	membrane	MARK_AS_OVER_ANNOTATED	yes		GO:0016020 membrane is a broad parent of GO:0005886 plasma membrane, which is already annotated and more precisely describes the inner-membrane localization of MraY.
PSEPK	mutL	IPR002099,IPR013507,IPR014790	GO:0005524	ATP binding	ACCEPT	no		ATP binding is a well-established and conserved property of the MutL N-terminal GHKL ATPase domain, consistent with the InterPro domain architecture of this protein.
PSEPK	mutL	IPR002099,IPR013507	GO:0030983	mismatched DNA binding	ACCEPT	no		Consistent with the conserved MutL function in the MMR pathway; MutL contacts the mismatched DNA substrate within the ternary repair complex. Retained as supporting the core MMR function.
PSEPK	mutL	IPR038973	GO:0140664	ATP-dependent DNA damage sensor activity	KEEP_AS_NON_CORE	yes		The activity is consistent with the established mechanism of MutL as an ATP-driven coordinator within MMR, but it is secondary to the core mismatch repair, ATPase, and mismatched-DNA-binding annotations. Retained as non-core rather than removed.
PSEPK	mutS	IPR045076	GO:0140664	ATP-dependent DNA damage sensor activity	ACCEPT	no		Accurately describes MutS as an ATP-dependent sensor that detects DNA mismatches/distortions and transmits the signal; well supported by the family mechanism. Core function.
PSEPK	nasA	IPR004737	GO:0015113	nitrite transmembrane transporter activity	KEEP_AS_NON_CORE	yes		Nitrite transport is plausible from the shared nitrate/nitrite porter family assignment, but it is not as strongly grounded as nitrate uptake in KT2440. Available strain-specific evidence points much more directly to a role in nitrate assimilation, and the current non-primary BarSeq evidence argues against making nitrite transport the core call.
PSEPK	nasA	IPR011701,IPR020846	GO:0022857	transmembrane transporter activity	MARK_AS_OVER_ANNOTATED	yes		This parent transporter term is correct but much less informative than the specific nitrate and possible nitrite transporter terms already present.
PSEPK	nasA	IPR004737	GO:0015707	nitrite transport	KEEP_AS_NON_CORE	yes		The transporter family allows this process annotation to remain plausible, but direct KT2440 evidence is not as specific for nitrite handling as it is for nitrate. This should be retained as a non-core possibility rather than treated as the main biological-process call.
PSEPK	nasA	IPR011701	GO:0055085	transmembrane transport	MARK_AS_OVER_ANNOTATED	yes		This broad transport process term is redundant given the more informative nitrate transmembrane transport and nitrate assimilation annotations.
PSEPK	nicA	IPR002888	GO:0046872	metal ion binding	MARK_AS_OVER_ANNOTATED	yes		Use the more specific Fe-S cluster term.
PSEPK	nicA	IPR001041,IPR036010	GO:0051536	iron-sulfur cluster binding	MARK_AS_OVER_ANNOTATED	yes		Prefer GO:0051537 for this subunit.
PSEPK	nicA	IPR006058	GO:0051537	2 iron, 2 sulfur cluster binding	ACCEPT	no		Retain as the subunit-specific function while modeling the full NicAB oxidoreductase activity as a contributed complex activity.
PSEPK	nicB	IPR009056,IPR036909	GO:0009055	electron transfer activity	KEEP_AS_NON_CORE	yes		Retain as a non-core mechanistic feature.
PSEPK	nicB	IPR008274,IPR037165	GO:0016491	oxidoreductase activity	MARK_AS_OVER_ANNOTATED	yes		Prefer the more specific oxidoreductase term.
PSEPK	nicB	IPR009056,IPR036909	GO:0020037	heme binding	KEEP_AS_NON_CORE	yes		Retain as non-core cofactor binding.
PSEPK	nicC	IPR002938	GO:0071949	FAD binding	KEEP_AS_NON_CORE	yes		Retain as non-core cofactor binding.
PSEPK	nicP	IPR005318	GO:0016020	membrane	MODIFY	yes	GO:0009279 cell outer membrane	NicP belongs to the outer membrane porin (Opr) family; GO:0009279 (cell outer membrane) is more specific than generic membrane for a Gram-negative bacterial porin. Deep research notes that a porin is an outer membrane beta-barrel and that the porin annotation implies an outer-membrane location, though no direct localization experiment for NicP was found, so this is an inference rather than experimentally demonstrated.
PSEPK	nicR	IPR000835,IPR039422	GO:0003700	DNA-binding transcription factor activity	MODIFY	yes	GO:0001217 DNA-binding transcription repressor activity	Replace with the more specific repressor activity term. Falcon deep research confirms direct, sequence-specific DNA binding by purified NicR with mapped operator footprints, supporting repressor activity rather than a generic transcription factor term.
PSEPK	nicS	IPR001647	GO:0003677	DNA binding	KEEP_AS_NON_CORE	yes		NicS is a DNA-binding transcriptional regulator; the binding parent term is retained as background rather than the core function.
PSEPK	nicS	IPR050109	GO:0003700	DNA-binding transcription factor activity	MODIFY	yes	GO:0001217 DNA-binding transcription repressor activity	UniProt and the nic regulatory paper identify NicS as a repressor of the nicAB Pa promoter, and falcon deep research independently confirms NicS represses nicAB, so GO:0001217 (DNA-binding transcription repressor activity) is more specific than generic DNA-binding transcription factor activity.
PSEPK	nicS	IPR050109	GO:0006355	regulation of DNA-templated transcription	MODIFY	yes	GO:0045892 negative regulation of DNA-templated transcription	NicS represses nicAB transcription in the absence of nicotinate or 6-hydroxynicotinate, so negative regulation of DNA-templated transcription is the better process term. Falcon deep research reinforces that NicS gates expression of the upstream NA-hydroxylation step and that repression is relieved by NA and/or 6HNA effectors.
PSEPK	nicT	IPR011701	GO:0055085	transmembrane transport	ACCEPT	no		The MFS transporter-family evidence and the nic-cluster/operon context support a transmembrane transport process. The falcon deep research argues, from operon context and the biochemically demonstrated nicotinate-uptake function of the related NiaP family, that NicT most plausibly imports nicotinate; this remains an inference pending a direct uptake assay, so the generic process term is retained; a substrate-specific process term such as GO:2001142 (nicotinate transport) may be warranted pending experimental confirmation of the substrate.
PSEPK	ntrC	IPR002078,IPR010114	GO:0005524	ATP binding	ACCEPT	no		ATP binding is a core mechanistic requirement for enhancer-binding proteins such as NtrC, even though the GOA entry stops short of naming ATPase activity.
PSEPK	ntrC	IPR002078	GO:0006355	regulation of DNA-templated transcription	MODIFY	yes	GO:0045893 positive regulation of DNA-templated transcription; GO:0045892 negative regulation of DNA-templated transcription	A generic transcription-regulation term obscures the experimentally demonstrated dual activator/repressor behavior of NtrC.
PSEPK	ntrC	IPR002197	GO:0043565	sequence-specific DNA binding	ACCEPT	no		Sequence-specific promoter recognition is fundamental to the direct-regulator role of NtrC.
PSEPK	opmQ	IPR003423	GO:0015562	efflux transmembrane transporter activity	ACCEPT	no		OpmQ is an outer-membrane component of a tripartite efflux system that exports pyoverdine; GO lacks a pyoverdine-specific efflux transporter term.
PSEPK	opmQ	IPR010131	GO:0016020	membrane	MARK_AS_OVER_ANNOTATED	yes		GO:0009279 provides the specific bacterial outer-membrane location.
PSEPK	opmQ	IPR010131	GO:0022857	transmembrane transporter activity	MARK_AS_OVER_ANNOTATED	yes		GO:0015562 captures the efflux directionality of the PvdRT-OpmQ system.
PSEPK	opmQ	IPR003423,IPR010131	GO:0055085	transmembrane transport	MARK_AS_OVER_ANNOTATED	yes		GO:0055085 is the broad transmembrane-transport parent. The separate NEW GO:0015891 siderophore transport entry with IMP/PMID:30346656 evidence captures the specific pyoverdine secretion/recycling process; marking this parent as over-annotated avoids generating a second GO:0015891 annotation through MODIFY.
PSEPK	oprD	IPR005318	GO:0016020	membrane	MODIFY	yes	GO:0019867 outer membrane	"The protein is an established OprD/Occ-family outer membrane porin; the generic ""membrane"" term under-specifies its known compartment. GO:0019867 (outer membrane) is the appropriate, evidence-consistent refinement."
PSEPK	oprE	IPR005318	GO:0016020	membrane	MODIFY	yes	GO:0019867 outer membrane	The generic membrane term (GO:0016020) is correct but uninformatively broad for a Gram-negative outer membrane porin. The OprD/Occ family is an outer membrane beta-barrel family, and OprE is experimentally and proteomically associated with the outer membrane, justifying refinement to the outer membrane term.
PSEPK	oprF	IPR028974	GO:0005509	calcium ion binding	REMOVE	yes		I found no direct biochemical evidence that KT2440 OprF binds calcium. The annotation appears to come from a low-specificity domain match in the acidic C-terminal region and does not reflect the conserved core function of the OprF family.
PSEPK	pal	IPR006664,IPR006690	GO:0016020	membrane	MARK_AS_OVER_ANNOTATED	yes		GO:0009279 provides the more specific bacterial outer-membrane location.
PSEPK	pcaB	IPR008948,IPR020557	GO:0003824	catalytic activity	MARK_AS_OVER_ANNOTATED	yes		The annotation is technically true but uninformative. GO:0047472 (3-carboxy-cis,cis-muconate cycloisomerase activity) captures the actual enzymatic function at the appropriate level of specificity.
PSEPK	pcaB	IPR012789	GO:0019619	3,4-dihydroxybenzoate catabolic process	ACCEPT	no		The term is specific enough and consistent with both the enzyme literature and UniProt pathway assignment. PcaB acts downstream of protocatechuate ring cleavage as part of the canonical protocatechuate branch of aromatic compound degradation.
PSEPK	pcaD	IPR026968	GO:0042952	beta-ketoadipate pathway	ACCEPT	no		The term is appropriately specific for the evolved biological role of this enzyme. PcaD catalyzes the enol-lactone hydrolysis step that feeds aromatic intermediates into beta-ketoadipate, and older pathway genetics explicitly place pcaDE in the shared P. putida beta-ketoadipate pathway.
PSEPK	pcaF	IPR016039	GO:0016746	acyltransferase activity	MARK_AS_OVER_ANNOTATED	yes		The specific thiolase activity is already represented by GO:0033812, so this broad umbrella term adds little biological information.
PSEPK	pcaF	IPR002155,IPR012793,IPR020610,IPR020613,IPR020615,IPR020616,IPR020617	GO:0016747	acyltransferase activity, transferring groups other than amino-acyl groups	MARK_AS_OVER_ANNOTATED	yes		Pathway-specific curation should prefer the substrate-resolved thiolase term.
PSEPK	pcaF	IPR012793	GO:0019619	3,4-dihydroxybenzoate catabolic process	ACCEPT	no		Proteomics and classical pca pathway genetics support participation of PcaF in the protocatechuate branch of aromatic compound catabolism.
PSEPK	pcaG	IPR000627	GO:0003824	catalytic activity	MARK_AS_OVER_ANNOTATED	yes		GO:0018578 captures the relevant biochemical activity and substrate specificity. Retaining GO:0003824 does not add meaningful functional resolution.
PSEPK	pcaG	IPR012786,IPR015889	GO:0005506	iron ion binding	REMOVE	yes		The alpha chain contributes to the catalytic interface, but the iron-ligating residues defined for protocatechuate 3,4-dioxygenase are all on the beta subunit. This makes the iron-binding annotation a subunit-level overassignment for pcaG. Falcon deep research independently describes the catalytic Fe(III) as a 2-His/2-Tyr center, a holoenzyme-level cofactor property rather than an alpha-subunit function.
PSEPK	pcaG	IPR000627	GO:0008199	ferric iron binding	REMOVE	yes		This annotation confuses a complex-level cofactor requirement with the subunit-level molecular function of pcaG. The structural data support retaining the complex dioxygenase activity while dropping ferric-iron binding on the alpha chain. Falcon deep research reinforces this by describing the Fe(III) 2-His/2-Tyr center as a property of the assembled 3,4-PCD enzyme.
PSEPK	pcaG	IPR015889	GO:0016702	oxidoreductase activity, acting on single donors with incorporation of molecular oxygen, incorporation of two atoms of oxygen	MARK_AS_OVER_ANNOTATED	yes		The specific molecular function GO:0018578 already captures the relevant oxygen-incorporating chemistry and substrate identity. The parent oxidoreductase term is therefore redundant.
PSEPK	pcaH	IPR000627	GO:0003824	catalytic activity	MARK_AS_OVER_ANNOTATED	yes		The specific molecular function term GO:0018578 already captures the informative activity.
PSEPK	pcaH	IPR012785,IPR015889	GO:0005506	iron ion binding	MARK_AS_OVER_ANNOTATED	yes		GO:0008199 is the more informative child term for this enzyme system.
PSEPK	pcaH	IPR000627	GO:0008199	ferric iron binding	ACCEPT	no		Ferric iron is a defining catalytic cofactor of the protocatechuate 3,4-dioxygenase complex, and the falcon deep research places the Fe(III)-coordinating residues (two histidines and two tyrosines) within the beta subunit (PcaH) itself, so this is a genuine PcaH binding function rather than only a complex-level or family-level prediction.
PSEPK	pcaH	IPR015889	GO:0016702	oxidoreductase activity, acting on single donors with incorporation of molecular oxygen, incorporation of two atoms of oxygen	KEEP_AS_NON_CORE	yes		The annotation is accurate but less informative than the specific enzyme activity term. The falcon deep research confirms the defining chemistry of this parent term (incorporation of both atoms of O2), so it is correct yet redundant with the specific GO:0018578 annotation.
PSEPK	pcaH	IPR012785	GO:0019619	3,4-dihydroxybenzoate catabolic process	ACCEPT	no		The annotation matches the immediate biological process supported by the strain-specific pathway literature, and the falcon deep research places PcaGH at the committed ring-cleavage step of the protocatechuate branch of the beta-ketoadipate pathway.
PSEPK	pcaK	IPR004746,IPR005829,IPR011701,IPR020846	GO:0022857	transmembrane transporter activity	MODIFY	yes	GO:0008028 monocarboxylic acid transmembrane transporter activity; GO:0015293 symporter activity	The generic transporter term should be replaced by terms that capture both substrate class and mechanism. The best existing GO terms are GO:0008028 monocarboxylic acid transmembrane transporter activity and GO:0015293 symporter activity. A still more specific 4-hydroxybenzoate transporter term does not appear to exist in GO and is proposed below.
PSEPK	pcaK	IPR004746,IPR005829,IPR011701	GO:0055085	transmembrane transport	MARK_AS_OVER_ANNOTATED	yes		GO:0055085 is a broad parent term that does not communicate substrate class or the special role of PcaK as an aromatic acid symporter. The existing GO:1905039 annotation captures the core transport process with better specificity.
PSEPK	pcaK	IPR004746,IPR005829	GO:0016020	membrane	MARK_AS_OVER_ANNOTATED	yes		The generic component term does not add useful information beyond the more specific plasma membrane annotation and should be treated as an automated parent-term over-annotation.
PSEPK	pcaQ	IPR012787	GO:0003677	DNA binding	KEEP_AS_NON_CORE	yes		Retain as a broad molecular function while treating DNA-binding transcription factor activity as the clearer annotation. The HTH lysR-type domain (UniProt FT DOMAIN 7..64) provides the DNA-binding capability.
PSEPK	pcaQ	IPR000847	GO:0003700	DNA-binding transcription factor activity	ACCEPT	no		The UniProt name, LysR-family assignment, and PcaQ-specific InterPro/TIGRFAM domain are consistent with a pathway transcription factor. Homology evidence (A. tumefaciens PcaQ) indicates an activator role, so the more specific GO:0001216 (DNA-binding transcription activator activity) is proposed as a refinement.
PSEPK	pcaQ	IPR012787	GO:0019619	3,4-dihydroxybenzoate catabolic process	MARK_AS_OVER_ANNOTATED	yes		PcaQ is a transcriptional regulator, not a catalytic enzyme in protocatechuate breakdown. A regulation term (positive regulation of transcription) is more appropriate than direct pathway participation. The InterPro2GO assignment of this catabolic-process term to a regulator reflects the pathway association, not enzymatic involvement.
PSEPK	pcaQ	IPR012787	GO:0045893	positive regulation of DNA-templated transcription	ACCEPT	no		The protein is annotated as a transcriptional regulator in the LysR family with the PcaQ-specific InterPro/TIGRFAM domain, and homology evidence indicates an activator role, supporting positive regulation of pathway gene transcription.
PSEPK	pcaY	IPR004090	GO:0004888	transmembrane signaling receptor activity	ACCEPT	no		Retain the receptor molecular-function annotation; experimentally supported by direct ligand binding to the LBD and transmembrane signaling architecture.
PSEPK	pcaY	IPR003122,IPR003660,IPR004089,IPR004090	GO:0007165	signal transduction	KEEP_AS_NON_CORE	yes		Retain as a non-core parent process; the specific signaling output of PcaY is captured by the chemotaxis (GO:0006935) and receptor (GO:0004888) annotations.
PSEPK	pcaY	IPR003660,IPR004089,IPR004090	GO:0016020	membrane	MARK_AS_OVER_ANNOTATED	yes		Retain GO:0005886 (plasma membrane) instead; the specific inner-membrane localization is the informative location.
PSEPK	pedH	IPR017512	GO:0016020	membrane	REMOVE	yes		Too vague and potentially misleading. PedH is a periplasmic protein, not membrane-associated. While it has a signal peptide for periplasmic targeting, it is a soluble enzyme in the periplasm, not membrane-bound.
PSEPK	pedH	IPR017512,IPR034119	GO:0016614	oxidoreductase activity, acting on CH-OH group of donors	KEEP_AS_NON_CORE	yes		Accurate but too general. This correctly describes the broad enzymatic activity but lacks specificity about the PQQ-dependence and cytochrome c as electron acceptor. The more specific term GO:0052934 is present and preferred.
PSEPK	pedH	IPR001479	GO:0030288	outer membrane-bounded periplasmic space	REMOVE	yes	GO:0042597 periplasmic space	Less accurate than GO:0042597. While PedH is in the periplasm, this term implies specific association with the outer membrane boundary. Bioinformatics analysis confirms PedH is a soluble enzyme (no TM regions in mature protein) that functions throughout the periplasmic space, not specifically at membrane interfaces. The hydrophobic region (aa 6-27) is the signal peptide, cleaved upon export.
PSEPK	pedI	IPR015590,IPR016160,IPR016161,IPR016162,IPR029510	GO:0016491	oxidoreductase activity	MARK_AS_OVER_ANNOTATED	yes		Generic redox activity is redundant here and obscures the more informative substrate-level aldehyde dehydrogenase function.
PSEPK	pede	IPR017512	GO:0016020	membrane	REMOVE	yes		PedE is a soluble periplasmic enzyme as stated in UniProt and confirmed by purification as a soluble His-tagged protein from E. coli lysates (PMID:28655819). The membrane annotation is an artifact of the InterPro mapping which does not distinguish soluble from membrane-bound PQQ-ADHs. This is the same conclusion reached for paralog PedH.
PSEPK	pede	IPR017512,IPR034119	GO:0016614	oxidoreductase activity, acting on CH-OH group of donors	ACCEPT	no		This accurately describes the chemical group acted upon by PedE. It is less specific than GO:0052934 but correctly captures the CH-OH donor specificity, which is a valid intermediate annotation from InterPro domain mapping.
PSEPK	pede	IPR001479	GO:0030288	outer membrane-bounded periplasmic space	REMOVE	yes	GO:0042597 periplasmic space	While PedE is indeed in the periplasm, the more specific outer-membrane-bounded qualifier is not supported by evidence. PedE is a freely soluble enzyme in the periplasmic space, not specifically localized to the outer membrane boundary. The correct annotation GO:0042597 (periplasmic space) is already present. Same conclusion as for PedH.
PSEPK	pgi1	IPR046348	GO:0097367	carbohydrate derivative binding	MARK_AS_OVER_ANNOTATED	yes		The term is an uninformative high-level binding parent; the specific catalytic function (GO:0004347) already entails substrate binding.
PSEPK	pgi1	IPR046348	GO:1901135	carbohydrate derivative metabolic process	MARK_AS_OVER_ANNOTATED	yes		A high-level metabolic parent that adds no specificity beyond the more precise process terms already annotated.
PSEPK	phaA	IPR011287	GO:0016746	acyltransferase activity	ACCEPT	no		The acyltransferase activity annotation is correct. PhaC1 is classified as EC 2.3.1.- and catalyzes acyl group transfer from CoA-linked substrates to polyester chains. While GO:0016747 would be slightly more specific, GO:0016746 is not wrong and accurately captures the molecular function. The InterPro domain match (IPR011287, PHA_synth_II) is a high-confidence match for this Class II PHA synthase.
PSEPK	phaA	IPR010941,IPR011287	GO:0042619	poly-hydroxybutyrate biosynthetic process	REMOVE	yes		This annotation is factually incorrect for P. putida PhaC1. The enzyme is a Class II PHA synthase that produces medium-chain-length PHAs (mcl-PHAs, C6-C14), not poly-hydroxybutyrate (PHB, C4). The GO term GO:0042619 explicitly describes PHB biosynthesis, defined as a polymer of beta-hydroxybutyrate. The InterPro2GO mapping that generates this annotation does not distinguish between Class I (PHB-producing) and Class II (mcl-PHA-producing) synthases. P. putida KT2440 does not produce PHB. No appropriate broader GO BP term for polyhydroxyalkanoate biosynthesis currently exists; this represents a gap in the GO ontology.
PSEPK	phaC	IPR011287	GO:0016746	acyltransferase activity	ACCEPT	no		Accept as the best currently available GO molecular-function term. It captures the correct transferase chemistry for PhaC-II, even though the true biological activity is more specifically PHA polymerization and would benefit from a dedicated synthase term in GO.
PSEPK	phaC	IPR010941,IPR011287	GO:0042619	poly-hydroxybutyrate biosynthetic process	MODIFY	yes	GO:0042621 poly(3-hydroxyalkanoate) biosynthetic process	Too narrow for the KT2440 enzyme. Pseudomonas putida KT2440 is described as an mcl-PHA producer, and the relevant pathway literature places PhaC2 in poly(3-hydroxyalkanoate) polymerization rather than specifically poly-hydroxybutyrate synthesis. Falcon deep research reinforces this; it explicitly assigns PhaC2/PP_5005 to the class II PhaC family that produces medium-chain-length (C6-C14) PHA in pseudomonads, and notes the protein is granule-associated rather than a PHB (scl-PHA) synthase. Replace with the existing broader GO term for poly(3-hydroxyalkanoate) biosynthesis.
PSEPK	pheA	IPR002701,IPR036263,IPR036979	GO:0046417	chorismate metabolic process	KEEP_AS_NON_CORE	yes		Accurate; chorismate is the substrate of the chorismate mutase step. A broader metabolic grouping than L-phenylalanine biosynthesis. Retained as accurate but non-core.
PSEPK	phhB	IPR001533,IPR036428	GO:0006729	tetrahydrobiopterin biosynthetic process	ACCEPT	no		UniProt states that PhhB is involved in tetrahydrobiopterin biosynthesis and gives the corresponding dehydratase reaction. The falcon deep-research synthesis clarifies that PhhB/PCD is a cofactor recycling enzyme that regenerates the reduced tetrahydropterin pool consumed by aromatic amino acid hydroxylases, not a de novo biosynthetic enzyme; it also notes that in pseudomonads the physiological reduced cofactor is most plausibly tetrahydromonapterin (MH4) rather than tetrahydrobiopterin (BH4). The current GOA term GO:0006729 is therefore usable but broad and slightly mismatched on the specific pterin; a recycling-specific process term is left as a proposed term / suggested ontology question rather than asserted here. Kept as ACCEPT because GO:0006729 is the closest available curated process term and is supported by the UniProt function statement.
PSEPK	phnW	IPR012703	GO:0019700	organic phosphonate catabolic process	ACCEPT	no		UniProt identifies PhnW as involved in phosphonate degradation, and the enzyme reaction produces phosphonoacetaldehyde, the activated intermediate required for downstream C-P bond cleavage (by PhnX or PhnA). The deep-research synthesis confirms PhnW is the upstream/committing enzyme of the conserved PhnWX and PhnWAY AEP catabolic routes.
PSEPK	pilA	IPR001082	GO:0007155	cell adhesion	ACCEPT	no		Adhesion is a well-established function of type IV pili and of the major pilin subunit. The InterPro2GO inference from the Pilin domain (IPR001082) is biologically appropriate, and surface-attachment-induced pilin expression in P. putida supports an adhesion role. The term is general but not incorrect; a more specific adhesion-during-biofilm term could be considered if experimental evidence in KT2440 were available.
PSEPK	pilA	IPR001082	GO:0009289	pilus	MODIFY	yes	GO:0044096 type IV pilus	"The generic ""pilus"" term is correct but under-specific. PilA belongs to the N-Me-Phe (type IVa) pilin family and assembles into a type IV pilus, so the more informative child term GO:0044096 (type IV pilus) better captures the localization."
PSEPK	pilA	IPR000983	GO:0015627	type II protein secretion system complex	REMOVE	yes		The T4P major pilin and T2SS major pseudopilin share an ancestral pilin fold and InterPro signature, which causes InterPro2GO to over-propagate T2SS terms onto type IV pilins. PilA (PP_0634) is the major pilin of the type IV pilus system; its structural component is the type IV pilus, not the T2SS complex. This is a domain-homology over-annotation and should be removed.
PSEPK	pilA	IPR000983	GO:0015628	protein secretion by the type II secretion system	REMOVE	yes		This BP term is inferred from the shared pilin/pseudopilin domain signature and does not reflect PilA's actual role. PilA builds the type IV pilus and participates in type IV pilus assembly and twitching motility, not type II secretion. Remove as a domain-homology over-annotation; the appropriate processes (type IV pilus assembly, type IV pilus-dependent motility) are proposed as new terms.
PSEPK	pobA	IPR012733	GO:0043639	benzoate catabolic process	REMOVE	yes		There is no evidence here for direct participation in unsubstituted benzoate catabolism, and the annotation likely arose from family-level transfer rather than the actual substrate handled by PobA.
PSEPK	pobA	IPR012733	GO:0050660	flavin adenine dinucleotide binding	ACCEPT	no		FAD binding is a direct, mechanistically central molecular property of the enzyme and is well supported by structural evidence.
PSEPK	pobA	IPR002938	GO:0071949	FAD binding	REMOVE	yes		GO:0050660 is the clearer and more descriptive FAD-binding term, so GO:0071949 is best treated as a redundant duplicate here.
PSEPK	ppc	IPR021135,IPR022805	GO:0006099	tricarboxylic acid cycle	MARK_AS_OVER_ANNOTATED	yes		PEPC supports TCA cycle function anaplerotically but does not participate in the cycle's reactions; the more precise process annotations (oxaloacetate metabolic process, carbon fixation) better capture the actual role.
PSEPK	ppk	IPR003414	GO:0009358	polyphosphate kinase complex	KEEP_AS_NON_CORE	yes		The annotation is not wrong (PPK1 functions as a homo-oligomer), but it is a generic InterPro2GO inference without organism-specific complex evidence and is not the core descriptor of the gene's activity. Retained as non-core rather than removed, per guidance against over-ruling electronic CC mappings that are biologically reasonable.
PSEPK	ppsA	IPR002192,IPR013815	GO:0005524	ATP binding	KEEP_AS_NON_CORE	yes		Correct supporting molecular function. PEP synthase binds and hydrolyzes ATP (to AMP + phosphate) as the phosphoryl donor; the N-terminal PPDK AMP/ATP-binding domain (InterPro IPR002192, IPR013815) and the ATP-binding keyword support this. Kept as non-core because it describes a substrate-binding capability subsidiary to the specific catalytic activity.
PSEPK	ppsA	IPR002192	GO:0016301	kinase activity	MARK_AS_OVER_ANNOTATED	yes		General kinase/phosphotransfer term derived from the InterPro PPDK AMP/ATP-binding signature (IPR002192). It is correct in that PEP synthase transfers a phosphoryl group, but it is uninformative relative to the specific pyruvate, water dikinase activity already captured.
PSEPK	ppsA	IPR000121,IPR008279,IPR018274,IPR023151,IPR036637	GO:0016772	transferase activity, transferring phosphorus-containing groups	KEEP_AS_NON_CORE	yes		A more specific parent describing the phosphoryl-transfer chemistry, derived from InterPro PEP-utiliser signatures (IPR000121, IPR008279, etc.). Correct but a generalization of the precise pyruvate, water dikinase activity; kept as a non-core supporting term.
PSEPK	pqqE	IPR000385,IPR006638,IPR007197	GO:0003824	catalytic activity	MARK_AS_OVER_ANNOTATED	yes		Retain the specific cyclase and cofactor-binding terms instead of emphasizing generic catalytic activity. Deep research confirms PqqE has a precise, well-characterized radical-SAM peptide cyclase activity that is far more informative than the root catalytic term.
PSEPK	pqqE	IPR000385	GO:0046872	metal ion binding	MARK_AS_OVER_ANNOTATED	yes		Prefer GO:0051539 4 iron, 4 sulfur cluster binding. Deep research confirms the functionally relevant metal centers are iron-sulfur clusters, not generic mononuclear metal ions.
PSEPK	pqqE	IPR006638,IPR007197	GO:0051536	iron-sulfur cluster binding	KEEP_AS_NON_CORE	yes		Retain as a broad parent while treating GO:0051539 as the core cofactor term. It usefully covers the auxiliary [2Fe-2S] cluster that GO:0051539 alone does not.
PSEPK	pqqE	IPR000385,IPR011843	GO:0051539	4 iron, 4 sulfur cluster binding	ACCEPT	no		The [4Fe-4S] cluster is mechanistically central to radical-SAM peptide cross-linking.
PSEPK	pqqF	IPR001431,IPR011844	GO:0006508	proteolysis	KEEP_AS_NON_CORE	yes		The more informative biological process is pyrroloquinoline quinone biosynthesis; generic proteolysis captures only the chemistry, not the pathway context in which PqqF processes PqqA.
PSEPK	pqqF	IPR011844	GO:0008270	zinc ion binding	KEEP_AS_NON_CORE	yes		The core function is the pathway metalloendopeptidase activity, with zinc binding as a supporting cofactor feature required for catalysis.
PSEPK	pqqF	IPR011249	GO:0046872	metal ion binding	MARK_AS_OVER_ANNOTATED	yes		Prefer the more specific zinc ion binding term for the cofactor feature; generic metal ion binding adds no information beyond GO:0008270.
PSEPK	prs	IPR000842	GO:0009156	ribonucleoside monophosphate biosynthetic process	MARK_AS_OVER_ANNOTATED	yes		GO:0006015 (PRPP biosynthesis) is the more specific direct biological process. The deep research describes PRPP as a precursor metabolite for nucleotide biosynthesis rather than Prs directly performing nucleoside monophosphate synthesis.
PSEPK	prs	IPR005946	GO:0009165	nucleotide biosynthetic process	MARK_AS_OVER_ANNOTATED	yes		Prs directly synthesizes PRPP, a precursor for nucleotide biosynthesis; GO:0006015 is the specific process. The deep research frames PRPP as a central activated-ribose donor feeding nucleotide pathways.
PSEPK	pta	IPR004614	GO:0016407	acetyltransferase activity	MARK_AS_OVER_ANNOTATED	yes		GO:0016407 is a broad ancestor of GO:0008959 (phosphate acetyltransferase activity), which is already annotated with a specific evidence trail. The general term adds no information beyond the precise term and is an InterPro2GO over-generalization.
PSEPK	pta	IPR002505	GO:0016746	acyltransferase activity	MARK_AS_OVER_ANNOTATED	yes		GO:0016746 (transferring acyl groups) is an even broader ancestor of GO:0008959. It is redundant with, and far less informative than, the specific phosphate acetyltransferase activity term. Over-annotation from InterPro2GO mapping.
PSEPK	ptxS	IPR000843,IPR010982	GO:0003677	DNA binding	MARK_AS_OVER_ANNOTATED	yes		Generic DNA binding is uninformative for a sequence-specific repressor; the more specific cis-regulatory region binding and repressor activity terms better capture the function.
PSEPK	pvdD	IPR001242	GO:0003824	catalytic activity	MODIFY	yes	GO:1904091 non-ribosomal peptide synthetase activity	Generic catalytic activity is uninformative for a multimodular NRPS. Falcon deep research confirms PvdD is a pyoverdine-pathway NRPS that assembles peptide via a thiotemplate mechanism, so the specific NRPS activity term better captures its molecular function.
PSEPK	pvdE	IPR003439,IPR005898,IPR011527,IPR036640	GO:0005524	ATP binding	MARK_AS_OVER_ANNOTATED	yes		Correct but too generic. PvdE contains a canonical ABC transporter nucleotide-binding domain and necessarily binds ATP, but this parent term is much less informative than the existing transporter activity annotations.
PSEPK	pvdE	IPR005898	GO:0015833	peptide transport	MODIFY	yes	GO:0015891 siderophore transport	Only partially satisfactory. PvdE probably exports a peptidyl pyoverdine precursor, so the annotation is not entirely wrong, but the biologically relevant process is siderophore-related precursor traffic in the pyoverdine pathway rather than general peptide transport.
PSEPK	pvdE	IPR005898,IPR011527,IPR036640	GO:0016020	membrane	REMOVE	yes		Too generic to be useful once GO:0005886 plasma membrane is present.
PSEPK	pvdE	IPR003439	GO:0016887	ATP hydrolysis activity	KEEP_AS_NON_CORE	yes		Correct but generic. ATP hydrolysis is expected for an ABC exporter and is mechanistically necessary, but the transporter-function terms carry the main biological meaning.
PSEPK	pvdE	IPR011527	GO:0140359	ABC-type transporter activity	ACCEPT	no		Correct and currently the best general molecular function term. The domain architecture and transporter topology strongly support classification as an ABC exporter.
PSEPK	pvdE	IPR005898	GO:1904680	peptide transmembrane transporter activity	ACCEPT	no		Probably the closest available substrate-class molecular function term. The experimentally supported role of homologous PvdE proteins is export of a peptidyl pyoverdine precursor, although the term still misses the siderophore-precursor context and should be interpreted cautiously.
PSEPK	pvdH	IPR004637	GO:0008483	transaminase activity	KEEP_AS_NON_CORE	yes		Retain the broad parent as non-core while using GO:0045303 for the specific catalytic role.
PSEPK	pvdH	IPR005814	GO:0030170	pyridoxal phosphate binding	KEEP_AS_NON_CORE	yes		Retain as non-core support for the PLP-dependent transaminase mechanism.
PSEPK	pvdQ	IPR002692	GO:0016787	hydrolase activity	MODIFY	yes	GO:0016811 hydrolase activity, acting on carbon-nitrogen (but not peptide) bonds, in linear amides	PvdQ is an Ntn-hydrolase that cleaves the amide bond of N-acyl-homoserine lactones (EC 3.5.1.97). The more specific child term GO:0016811 captures this and is also annotated, so the bare grandparent should be replaced by the specific term.
PSEPK	pvdQ	IPR023343	GO:0016811	hydrolase activity, acting on carbon-nitrogen (but not peptide) bonds, in linear amides	ACCEPT	no		This is the most specific molecular-function term available in GO for AHL acylase activity (there is no dedicated 'acyl-homoserine lactone acylase activity' term; note GO:0102007 is a lactonohydrolase, a different reaction). Consistent with UniProt EC 3.5.1.97 and the Ntn-hydrolase mechanism of the PvdQ family.
PSEPK	pvdQ	IPR002692	GO:0017000	antibiotic biosynthetic process	MODIFY	yes	GO:0002049 pyoverdine biosynthetic process	The IEA InterPro mapping applies a generic 'antibiotic biosynthetic process' to S45 peptidases (the family includes penicillin/beta-lactam acylases), but pyoverdine is an iron-chelating siderophore, not an antibiotic. The supported biological role of PvdQ is periplasmic maturation of the pyoverdine precursor. Replace with the specific pyoverdine biosynthesis term.
PSEPK	pvdS	IPR013249	GO:0003677	DNA binding	ACCEPT	no		DNA binding is a valid parent annotation for a sigma factor. Although GO:0016987 is more informative, GO:0003677 is still correct and not misleading here.
PSEPK	pvdS	IPR007627,IPR013249,IPR013325,IPR014284	GO:0003700	DNA-binding transcription factor activity	MODIFY	yes	GO:0016987 sigma factor activity	Sigma factors are better annotated with GO:0016987 sigma factor activity. That term captures the defining molecular role of PvdS as the promoter-recognition subunit of RNA polymerase.
PSEPK	pvdS	IPR007627,IPR013249,IPR013325,IPR014284	GO:0006352	DNA-templated transcription initiation	ACCEPT	no		DNA-templated transcription initiation is the central step at which sigma factors act, so this annotation is specific and mechanistically correct.
PSEPK	pvdT	IPR003439,IPR017871	GO:0005524	ATP binding	KEEP_AS_NON_CORE	yes		Retain as non-core nucleotide binding.
PSEPK	pvdT	IPR003838	GO:0016020	membrane	MARK_AS_OVER_ANNOTATED	yes		Retain GO:0005886 instead.
PSEPK	pvdT	IPR003439,IPR017871	GO:0016887	ATP hydrolysis activity	ACCEPT	no		Retain as a core molecular-function annotation directly supported by biochemical assay of purified PvdT.
PSEPK	pyrG	IPR004468,IPR017456	GO:0006221	pyrimidine nucleotide biosynthetic process	MARK_AS_OVER_ANNOTATED	yes		The de novo CTP biosynthetic process annotation is more specific and should be preferred.
PSEPK	qhnDH	IPR015084	GO:0016638	oxidoreductase activity, acting on the CH-NH2 group of donors	MARK_AS_OVER_ANNOTATED	yes		GO:0030058 (aliphatic amine dehydrogenase activity) captures the substrate class and dehydrogenase reaction more precisely than the CH-NH2 oxidoreductase parent.
PSEPK	recA	IPR020584,IPR020587,IPR020588	GO:0003677	DNA binding	KEEP_AS_NON_CORE	yes		Correct but general. RecA's biologically meaningful binding activities are single-stranded DNA binding (GO:0003697) and damaged DNA binding (GO:0003684), which are separately annotated and capture the core function more precisely. Retained as a true but non-core parent term.
PSEPK	recA	IPR020584,IPR020587	GO:0006259	DNA metabolic process	KEEP_AS_NON_CORE	yes		Correct but very general; the specific processes (DNA recombination, DNA repair, SOS response) are separately annotated and better represent the gene's function. Retained as a true parent term.
PSEPK	recA	IPR020588	GO:0140664	ATP-dependent DNA damage sensor activity	ACCEPT	no		Appropriate molecular-function term for RecA's role as the SOS damage sensor that triggers LexA co-protease activity; consistent with InterPro mapping and RecA biology.
PSEPK	recB	IPR004586	GO:0006281	DNA repair	KEEP_AS_NON_CORE	yes		Correct but general; subsumed by GO:0000724.
PSEPK	retS	IPR003661,IPR036097	GO:0000155	phosphorelay sensor kinase activity	ACCEPT	no		This is the best-supported core molecular function for retS. KEGG assigns PP_4824 to the RetS ortholog group, and UniProt domain architecture matches a membrane hybrid sensor kinase with a histidine kinase catalytic module and receiver domains.
PSEPK	retS	IPR001789	GO:0000160	phosphorelay signal transduction system	ACCEPT	no		Accept as the core biological-process-level description. RetS is a hybrid two-component sensor kinase, and the KT2440 literature places it upstream in the Gac/RetS signaling network that controls K1-T6SS gene expression.
PSEPK	retS	IPR003661,IPR036097	GO:0007165	signal transduction	KEEP_AS_NON_CORE	yes		Correct but generic. The phosphorelay-specific term GO:0000160 better captures the core signaling mechanism, so this broad parent is retained only as non-core context.
PSEPK	retS	IPR004358	GO:0016772	transferase activity, transferring phosphorus-containing groups	MARK_AS_OVER_ANNOTATED	yes		The specific kinase activities already capture the meaningful molecular function. Retaining this broad parent term would reduce interpretability without adding biological precision.
PSEPK	rlmE	IPR002877,IPR015507	GO:0008168	methyltransferase activity	MARK_AS_OVER_ANNOTATED	yes		GO:0008650 (rRNA uridine-2'-O-ribose methyltransferase activity) captures the specific rRNA substrate and modified nucleotide. Falcon deep research confirms RlmE is a SAM-dependent RNA 2'-O-methyltransferase specific for the 23S rRNA ribose 2'-hydroxyl.
PSEPK	rlmH	IPR003742	GO:0006364	rRNA processing	MARK_AS_OVER_ANNOTATED	yes		GO:0031167 (rRNA methylation), also present in GOA, directly captures the modification process. RlmH performs a post-transcriptional base modification on the assembled ribosome rather than rRNA processing/maturation cleavage steps.
PSEPK	rlmH	IPR003742	GO:0008168	methyltransferase activity	MARK_AS_OVER_ANNOTATED	yes		GO:0070038 captures the exact rRNA pseudouridine N3-methyltransferase activity and should be preferred over the high-level parent term.
PSEPK	rnc	IPR011907	GO:0003723	RNA binding	MARK_AS_OVER_ANNOTATED	yes		RNA binding is a generic parent of double-stranded RNA binding (GO:0003725), which is already annotated and better captures the substrate-recognition activity mediated by the DRBM domain.
PSEPK	rnz	IPR013471	GO:0016891	RNA endonuclease activity producing 5'-phosphomonoesters, hydrolytic mechanism	MARK_AS_OVER_ANNOTATED	yes		GO:0042781 (3'-tRNA processing endoribonuclease activity) captures the tRNA 3'-processing substrate and product context and is the appropriate specific molecular function.
PSEPK	rpoD	IPR000943,IPR007624,IPR007627,IPR007630,IPR007631,IPR009042,IPR013325,IPR014284	GO:0003700	DNA-binding transcription factor activity	MARK_AS_OVER_ANNOTATED	yes		Over-annotation arising from a broad InterPro-to-GO mapping. Sigma factor activity (GO:0016987) is the appropriate, mutually-exclusive molecular function for a sigma factor, so GO:0003700 should not be retained as a core function.
PSEPK	rpoD	IPR000943,IPR007127,IPR007624,IPR007627,IPR007630,IPR007631,IPR009042,IPR012760,IPR013325,IPR014284	GO:0006355	regulation of DNA-templated transcription	KEEP_AS_NON_CORE	yes		True but general; the specific initiation processes (GO:0006352 and GO:2000142) better capture the core function. Retained as non-core.
PSEPK	rpoH	IPR000943,IPR007627,IPR007630,IPR012759,IPR013325,IPR014284	GO:0003700	DNA-binding transcription factor activity	REMOVE	yes		GO has an explicit convention that sigma factors are not DNA-binding transcription factors (GO:0003700) but rather are captured by GO:0016987 sigma factor activity, which is already annotated here. GO:0003700 is the wrong molecular function class for a sigma factor and is redundant/misleading. The correct MF term is present.
PSEPK	rpoH	IPR000943,IPR007627,IPR007630,IPR012759,IPR013325,IPR014284	GO:0006355	regulation of DNA-templated transcription	KEEP_AS_NON_CORE	yes		Correct and consistent with sigma factor biology, but a broad regulatory term. The more specific GO:0006352 (transcription initiation) and GO:2000142 (regulation of transcription initiation) better capture the precise role; retain as non-core context.
PSEPK	rpoN	IPR007046	GO:0003677	DNA binding	MARK_AS_OVER_ANNOTATED	yes		Retain the more specific GO:0016987 (sigma factor activity) and GO:0000976 (cis-regulatory region binding) instead of generic DNA binding.
PSEPK	rpoN	IPR007046	GO:0006352	DNA-templated transcription initiation	ACCEPT	no		Retain the transcription initiation process annotation; this is a core part of sigma-factor function.
PSEPK	rpoN	IPR000394	GO:0016987	sigma factor activity	ACCEPT	no		Retain as the precise molecular-function annotation for this gene.
PSEPK	rpoS	IPR000943,IPR007624,IPR007627,IPR007630,IPR009042,IPR012761,IPR013325,IPR014284	GO:0003700	DNA-binding transcription factor activity	MODIFY	yes	GO:0016987 sigma factor activity	Sigma factor activity is the exact and more informative child term for RpoS.
PSEPK	rsmG	IPR003682	GO:0008649	rRNA methyltransferase activity	MARK_AS_OVER_ANNOTATED	yes		The specific term GO:0070043 captures the modified base (guanine) and N7 position class and is already present in GOA. The deep research confirms the reaction is transfer of a methyl group from SAM/AdoMet to the N7 atom of guanine on 16S rRNA, so the precise guanine-N7 term should be the representative molecular function and this generic rRNA methyltransferase parent is redundant.
PSEPK	ruvB	IPR004605,IPR008823	GO:0003677	DNA binding	MARK_AS_OVER_ANNOTATED	yes		GO:0003677 is a general parent term; the specific child GO:0000400 (four-way junction DNA binding) more accurately describes RuvB's function and is already annotated, making the generic term redundant and over-general.
PSEPK	ruvB	IPR004605,IPR008823,IPR008824	GO:0009378	four-way junction helicase activity	ACCEPT	no		ATP-dependent Holliday junction branch migration (four-way junction helicase activity) is the core molecular function of RuvB within RuvAB, supported by the conserved AAA+ motor architecture and structural/biochemical studies of RuvB.
PSEPK	sdhA	IPR003952,IPR015939,IPR037099	GO:0016491	oxidoreductase activity	KEEP_AS_NON_CORE	yes		Correct but uninformative high-level term; subsumed by the specific EC 1.3.5.1 annotation. Retain as non-core.
PSEPK	sdhA	IPR011281	GO:0160308	succinate dehydrogenase (FAD) activity	ACCEPT	no		Accurately captures the FAD-coupled catalytic step intrinsic to the SdhA subunit; complementary to the holo-enzyme quinone-coupled term GO:0008177. Both are valid and informative.
PSEPK	secA	IPR000185	GO:0006886	intracellular protein transport	MARK_AS_OVER_ANNOTATED	yes		Broad parent biological process term assigned by InterPro2GO. Correct in the sense that SecA moves proteins to/across the membrane, but far less informative than the specific GO:0043952 (protein transport by the Sec complex) and GO:0065002 also annotated. Marking as over-annotated relative to the precise child terms.
PSEPK	secA	IPR011115,IPR011116,IPR011130,IPR036670	GO:0016020	membrane	MARK_AS_OVER_ANNOTATED	yes		Generic membrane parent term assigned by InterPro2GO. Correct but uninformative relative to the specific plasma membrane (GO:0005886) annotation. Marking as over-annotated.
PSEPK	secA	IPR011115,IPR011116,IPR011130,IPR036670	GO:0017038	protein import	MARK_AS_OVER_ANNOTATED	yes		"InterPro2GO-assigned term that mis-states the directionality of SecA function. SecA drives protein export/secretion (translocation out of the cytoplasm across the inner membrane) and membrane insertion, not import; the UniProt FUNCTION describes transfer of proteins into and across the membrane during export. The directional ""import"" framing is not appropriate for SecA, so this annotation is over-annotated/imprecise relative to the export and Sec-complex transport terms."
PSEPK	sodB	IPR001189,IPR019831,IPR019832,IPR019833	GO:0006801	superoxide metabolic process	MODIFY	yes	GO:0019430 removal of superoxide radicals	The child term `removal of superoxide radicals` better captures the process directly carried out by superoxide dismutase.
PSEPK	sodB	IPR001189,IPR019831,IPR019832,IPR019833	GO:0046872	metal ion binding	MODIFY	yes	GO:0005506 iron ion binding	`iron ion binding` is the correct specific cofactor-binding term for this protein.
PSEPK	ssuD	IPR011251,IPR036661	GO:0016705	oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen	MARK_AS_OVER_ANNOTATED	yes		The exact substrate-specific monooxygenase term GO:0008726 captures the same activity more informatively, so this broad oxygenase parent is redundant over-annotation for the core molecular function.
PSEPK	sucA	IPR001017,IPR011603	GO:0016624	oxidoreductase activity, acting on the aldehyde or oxo group of donors, disulfide as acceptor	KEEP_AS_NON_CORE	yes		This is a parent/more general molecular function term covering the E1 oxidoreductase chemistry (oxo-group donor, lipoyl-disulfide acceptor). It is not wrong, but it is a less informative generalization of the specific E1 activity already captured by GO:0004591. Keeping as non-core to avoid redundancy with the precise term.
PSEPK	sucA	IPR011603	GO:0030976	thiamine pyrophosphate binding	ACCEPT	no		SucA is a ThDP (thiamine diphosphate)-dependent decarboxylase; the UniProt cofactor annotation lists thiamine diphosphate, and the InterPro signature (IPR011603, THDP-binding fold) supports this. Accept as a supporting molecular function.
PSEPK	sucC	IPR005811	GO:0003824	catalytic activity	MARK_AS_OVER_ANNOTATED	yes		GO:0003824 is an uninformative high-level term superseded by the specific GO:0004775 (succinate-CoA ligase (ADP-forming) activity) annotation. Not useful as a representation of the gene's function.
PSEPK	sucC	IPR011761	GO:0046872	metal ion binding	MARK_AS_OVER_ANNOTATED	yes		GO:0046872 is a generic parent of GO:0000287 (magnesium ion binding), which is the precise and informative annotation. The general term adds no information.
PSEPK	surA	IPR023034	GO:0030288	outer membrane-bounded periplasmic space	ACCEPT	no		The protein is periplasmic and capable of associating with the outer membrane; this is the more specific (correct) location term for a Gram-negative periplasmic chaperone.
PSEPK	surA	IPR023034	GO:0042277	peptide binding	MARK_AS_OVER_ANNOTATED	yes		Generic binding term that is subsumed by the more specific and informative chaperone (unfolded protein binding) and PPIase activities already annotated.
PSEPK	surA	IPR023034	GO:0043165	Gram-negative-bacterium-type cell outer membrane assembly	ACCEPT	no		The protein's central role is the correct folding and assembly of outer membrane proteins, i.e. Gram-negative outer membrane biogenesis.
PSEPK	surA	IPR023034	GO:0050821	protein stabilization	KEEP_AS_NON_CORE	yes		Broad process term consistent with holdase activity but not the specific core function; retain as non-core.
PSEPK	thiI	IPR004114	GO:0003723	RNA binding	MARK_AS_OVER_ANNOTATED	yes		The tRNA binding and tRNA sulfurtransferase annotations are more informative.
PSEPK	thiI	IPR020536	GO:0004810	CCA tRNA nucleotidyltransferase activity	REMOVE	yes		ThiI is a sulfurtransferase/tRNA 4-thiouridine synthase, not a CCA-adding tRNA nucleotidyltransferase; this InterPro-derived row appears to be a bad parent/family propagation.
PSEPK	thiO	IPR012727	GO:0016491	oxidoreductase activity	MARK_AS_OVER_ANNOTATED	yes		Retain GO:0043799 (glycine oxidase activity) instead, which is the specific, experimentally supported molecular function.
PSEPK	thiO	IPR012727	GO:0050660	flavin adenine dinucleotide binding	KEEP_AS_NON_CORE	yes		Retain as cofactor binding supporting the catalytic glycine oxidase activity.
PSEPK	thrC	IPR000634	GO:0006520	amino acid metabolic process	MARK_AS_OVER_ANNOTATED	yes		Broad parent biological process term assigned by InterPro2GO from the Ser/Thr dehydratase PLP signature (IPR000634). It is correct but far less informative than the specific GO:0009088 (L-threonine biosynthetic process) that is also annotated. Marking as over-annotated relative to the precise child term.
PSEPK	thrC	IPR000634	GO:0030170	pyridoxal phosphate binding	ACCEPT	no		Supporting molecular function. Threonine synthase is PLP-dependent; the UniProt cofactor annotation lists pyridoxal 5'-phosphate and a Schiff-base lysine (MOD_RES at position 112) is documented. Accept.
PSEPK	tolC	IPR010130	GO:0019867	outer membrane	ACCEPT	no		The InterPro/OMF assignment and the LapE literature are fully consistent with outer membrane localization.
PSEPK	tolC	IPR003423,IPR010130	GO:0055085	transmembrane transport	MODIFY	yes	GO:0030253 protein secretion by the type I secretion system	GO has a more precise biological process term for the experimentally characterized secretion pathway, which is preferable to the generic transport annotation.
PSEPK	trpD	IPR000312	GO:0016757	glycosyltransferase activity	MARK_AS_OVER_ANNOTATED	yes		Uninformative parent term that does not accurately describe the enzyme's function; the specific activity (GO:0004048) and its proper parent pentosyltransferase (GO:0016763) are already annotated. Retaining glycosyltransferase activity is redundant and potentially misleading.
PSEPK	ttgA	IPR006143	GO:0016020	membrane	REMOVE	yes		Retaining the generic membrane term adds little value once the more specific plasma membrane annotation is accepted. The broad InterPro-derived term obscures the fact that TtgA is specifically anchored to the bacterial inner membrane.
PSEPK	ttgA	IPR006143	GO:0022857	transmembrane transporter activity	MODIFY	yes	GO:0044325 transmembrane transporter binding	The tripartite pump as a whole enables transmembrane transport, but that activity should not be assigned directly to the non-transmembrane adaptor subunit. A better molecular-function proxy is GO:0044325 transmembrane transporter binding, with complex membership captured separately by GO:1902495.
PSEPK	ttgB	IPR004764	GO:0015562	efflux transmembrane transporter activity	ACCEPT	no		This is the core molecular function of TtgB. It is the substrate-translocating inner membrane component of the TtgABC RND efflux pump. InterPro mapping from IPR004764 is appropriate. Multiple publications confirm efflux transporter function: TtgABC overexpression causes multidrug resistance via efflux (PMID:32840000), TtgABC knockout compromises chloramphenicol resistance (PMID:22143519), and TtgB possesses multidrug-binding capacity (PMID:17498746).
PSEPK	ttgB	IPR001036,IPR004764	GO:0016020	membrane	ACCEPT	no		While this is a broad parent term and GO:0005886 (plasma membrane) is more specific, it is acceptable to retain IEA annotations at broader levels. The InterPro domains IPR001036 (Acriflavine resistance protein) and IPR004764 (MdtF-like) correctly map to membrane localization. TtgB has 12 predicted transmembrane helices confirming integral membrane insertion.
PSEPK	ttgB	IPR001036	GO:0022857	transmembrane transporter activity	ACCEPT	no		This is a correct but general parent term of GO:0015562 (efflux transmembrane transporter activity). Since both annotations are IEA, retaining the broader term from a different InterPro mapping (IPR001036 vs IPR004764) is acceptable. TtgB unambiguously has transmembrane transporter activity as the RND inner membrane component of the TtgABC efflux pump.
PSEPK	ttgC	IPR003423	GO:0015562	efflux transmembrane transporter activity	ACCEPT	no		Multiple lines of evidence support efflux function in KT2440. TtgABC is described as the major multidrug efflux pump in KT2440, ttgC abundance rises during phenol stress, and TtgC can also partner with ParXY in multidrug-resistant P. putida strains. Although the exact substrate range is context dependent, efflux transporter activity is the correct core molecular-function summary.
PSEPK	ttgC	IPR010131	GO:0016020	membrane	MARK_AS_OVER_ANNOTATED	yes		GO:0016020 is a high-level parent term that is superseded here by the more informative and better supported GO:0009279 cell outer membrane.
PSEPK	ttgC	IPR010131	GO:0022857	transmembrane transporter activity	MARK_AS_OVER_ANNOTATED	yes		The available evidence specifically supports export/efflux rather than generic transmembrane transporter activity, so GO:0015562 is the more informative annotation.
PSEPK	ttgC	IPR003423,IPR010131	GO:0055085	transmembrane transport	ACCEPT	no		KT2440 data connect ttgC/TtgABC to phenol adaptation, antibiotic resistance, and multidrug efflux. The broad biological-process term is conservative but justified until a single substrate-specific process can be supported without over-annotation.
PSEPK	ttgR	IPR001647,IPR013572	GO:0003677	DNA binding	KEEP_AS_NON_CORE	yes		DNA binding is true for this HTH regulator but is less specific than the transcription cis-regulatory region binding term, so it should be retained only as a broad non-core parent.
PSEPK	tyrB	IPR004838	GO:0003824	catalytic activity	MARK_AS_OVER_ANNOTATED	yes		"""catalytic activity"" is the MF root and conveys no specific information. The more precise terms GO:0008483 (transaminase activity) and GO:0004838 (L-tyrosine:2-oxoglutarate transaminase activity) capture the actual function."
PSEPK	tyrB	IPR000796	GO:0006520	amino acid metabolic process	MODIFY	yes	GO:0009072 aromatic amino acid family metabolic process	"The annotation is correct in essence but too high-level. tyrB acts specifically on aromatic amino acids (Tyr/Phe), so the more specific ""aromatic amino acid family metabolic process"" better reflects the characterized role while remaining defensible from family + genetic evidence. (Chorismate metabolic process is not appropriate: tyrB acts downstream of chorismate on the aromatic amino acids/2-oxoacids, not on chorismate itself.)"
PSEPK	uvrA	IPR004602	GO:0009380	excinuclease repair complex	ACCEPT	no		UvrA is a bona fide subunit of the excinuclease repair complex. The cellular component annotation correctly captures its assembly with UvrB (and the broader UvrABC system).
PSEPK	uvrA	IPR003439,IPR004602,IPR017871	GO:0016887	ATP hydrolysis activity	ACCEPT	no		ATP hydrolysis is a core, mechanistically essential molecular function of UvrA. It is directly supported by the ATPase description and the two ABC-transporter/P-loop nucleotide-binding domains, and is more specific than the generic 'catalytic activity'.
PSEPK	uvrB	IPR004807	GO:0009380	excinuclease repair complex	ACCEPT	no		Accurately reflects UvrB's role as a component of the UvrABC excinuclease complex; supported by the UniProt SUBUNIT annotation. Core cellular component.
PSEPK	uvrB	IPR006935	GO:0016787	hydrolase activity	MARK_AS_OVER_ANNOTATED	yes		GO:0016787 is an uninformative high-level parent of the more specific and also-annotated GO:0016887 (ATP hydrolysis activity). It adds no functional specificity beyond the ATPase annotation.
PSEPK	uvrB	IPR004807	GO:0016887	ATP hydrolysis activity	ACCEPT	no		ATP hydrolysis (ATPase activity) is a well-established core molecular function of UvrB, supported by the conserved helicase motifs and Walker A/B-containing helicase ATP-binding domain.
PSEPK	vanA	IPR015881	GO:0005506	iron ion binding	MARK_AS_OVER_ANNOTATED	yes		GO:0005506 is true in a broad sense, but GO:0051537 precisely captures the relevant cofactor-binding chemistry for this protein and should be preferred.
PSEPK	vanA	IPR044043	GO:0016491	oxidoreductase activity	MARK_AS_OVER_ANNOTATED	yes		The annotation is redundant with GO:0018489, which states the actual substrate and reaction class.
PSEPK	vanA	IPR015881,IPR017941,IPR036922	GO:0051537	2 iron, 2 sulfur cluster binding	ACCEPT	no		This is a specific, mechanistically relevant molecular function that explains how the oxygenase subunit supports catalytic turnover.
PSEPK	vanB	IPR001041,IPR036010	GO:0051536	iron-sulfur cluster binding	MARK_AS_OVER_ANNOTATED	yes		GO:0051537 captures the same feature more precisely and should be preferred as the core cofactor-binding annotation.
PSEPK	vanB	IPR006058	GO:0051537	2 iron, 2 sulfur cluster binding	ACCEPT	no		The UniProt record explicitly assigns a 2Fe-2S ferredoxin-type domain and corresponding InterPro/PROSITE signatures.
PSEPK	wspR	IPR001789	GO:0000160	phosphorelay signal transduction system	ACCEPT	no		Acceptable. WspR is the terminal output component of the Wsp surface-sensing phosphorelay/signaling system and transduces that signal into elevated c-di-GMP.
PSEPK	wspR	IPR013767	GO:0006355	regulation of DNA-templated transcription	MARK_AS_OVER_ANNOTATED	yes		Over-annotated. WspR does not appear to be a DNA-binding transcription regulator. Instead, it alters transcription indirectly through c-di-GMP signaling and the downstream FleQ/FleN regulatory system.
PSEPK	xylR	IPR002078	GO:0005524	ATP binding	KEEP_AS_NON_CORE	yes		ATP binding is mechanistically credible for XylR because the protein contains the canonical AAA+/sigma54 activator core and UniProt annotates explicit ATP-binding residues. The 1998 promoter-switch paper further shows that ATP enhances active XylR multimerization at the UAS. However, ATP binding is a generic mechanistic property rather than the most informative description of the evolved role of this regulator.
PSEPK	xylR	IPR002078	GO:0006355	regulation of DNA-templated transcription	MODIFY	yes	GO:0045893 positive regulation of DNA-templated transcription	This annotation captures the right general process class but is too broad. XylR is primarily a positive activator of the sigma54-dependent Pu and Ps promoters of the TOL system, although activated XylR also contributes to repression of the divergent Pr promoter. The more specific child term positive regulation of DNA-templated transcription better reflects the main curatable biology.
PSEPK	xylR	IPR002197	GO:0043565	sequence-specific DNA binding	ACCEPT	no		This is a core XylR function. The C-terminal D domain carries the DNA-binding structure/HTH motif, and activated XylR binds upstream activating sequences that overlap the divergent Pr/Ps control region to regulate transcriptional switching. Falcon deep research independently corroborates that the C-terminal D domain binds UAS via an HTH-type motif and that XylR acts at a distance through DNA looping, consistent with the canonical sigma54 bEBP enhancer architecture.
PSEPK	ydiJ	IPR004113,IPR016164	GO:0003824	catalytic activity	MARK_AS_OVER_ANNOTATED	yes		GO:0003824 is the generic parent of all enzyme activity. A specific MF term (GO:0051990) is available and supported, so the root term is an over-annotation that adds no functional information.
PSEPK	ydiJ	IPR016166	GO:0071949	FAD binding	MARK_AS_OVER_ANNOTATED	yes		Genuine cofactor binding (FAD COFACTOR line; FAD-binding PCMH-type domain), but generic to the family and not the core function once GO:0051990 is present.
PSEPK	zwf	IPR001282	GO:0016614	oxidoreductase activity, acting on CH-OH group of donors	MARK_AS_OVER_ANNOTATED	yes		GO:0004345 already captures the exact activity. Retaining this broader oxidoreductase term adds redundancy without improving biological precision.
RAMVA	RvY_00650	IPR024134	GO:0005507	copper ion binding	ACCEPT	no		All four canonical Cu-binding histidines are preserved at the sequence level. Copper binding is likely.
RAMVA	RvY_00650	IPR001424,IPR036423	GO:0006801	superoxide metabolic process	MARK_AS_OVER_ANNOTATED	yes		Inferred from SOD activity. Same caveats as the MF annotation.
RAMVA	RvY_00650	IPR001424,IPR036423	GO:0046872	metal ion binding	KEEP_AS_NON_CORE	yes		Parent term of the more specific Cu/Zn binding annotations. Both Cu and Zn binding are likely.
RAMVA	RvY_00651	IPR024134	GO:0005507	copper ion binding	ACCEPT	no		All four canonical Cu-binding histidine residues are preserved in the sequence. Copper binding is very likely.
RAMVA	RvY_00651	IPR001424,IPR036423	GO:0006801	superoxide metabolic process	KEEP_AS_NON_CORE	yes		Technically correct but less informative than GO:0019430. Kept as non-core.
RAMVA	RvY_00651	IPR001424,IPR036423	GO:0046872	metal ion binding	KEEP_AS_NON_CORE	yes		Redundant with the more specific Cu/Zn binding annotations. Kept as non-core.
RAMVA	RvY_01767	IPR001189,IPR019831,IPR019832,IPR019833	GO:0006801	superoxide metabolic process	ACCEPT	no		Standard biological process annotation for SOD enzymes.
RAMVA	RvY_01767	IPR001189,IPR019831,IPR019832,IPR019833	GO:0046872	metal ion binding	KEEP_AS_NON_CORE	yes		Parent term of GO:0030145 (manganese ion binding). Redundant with the more specific annotation.
RAMVA	RvY_03754	IPR024134	GO:0005507	copper ion binding	ACCEPT	no		All four canonical Cu-binding histidines are preserved at the sequence level. Copper binding is likely.
RAMVA	RvY_03754	IPR001424,IPR036423	GO:0006801	superoxide metabolic process	ACCEPT	no		Inferred from SOD activity annotation.
RAMVA	RvY_03754	IPR001424,IPR036423	GO:0046872	metal ion binding	KEEP_AS_NON_CORE	yes		Parent term of the more specific Cu/Zn binding annotations. Both Cu and Zn binding are likely.
RAMVA	RvY_03757	IPR024134	GO:0005507	copper ion binding	ACCEPT	no		All four canonical Cu-binding histidines are preserved at the sequence level. Copper binding is likely.
RAMVA	RvY_03757	IPR001424,IPR036423	GO:0006801	superoxide metabolic process	MARK_AS_OVER_ANNOTATED	yes		Inferred from SOD activity. Same caveats as the MF annotation.
RAMVA	RvY_03757	IPR001424,IPR036423	GO:0046872	metal ion binding	KEEP_AS_NON_CORE	yes		Parent term of the more specific Cu/Zn binding annotations. Both Cu and Zn binding are likely.
RAMVA	RvY_09480	IPR024134	GO:0005507	copper ion binding	ACCEPT	no		All four canonical Cu-binding histidines are preserved at the sequence level. Copper binding is likely.
RAMVA	RvY_09480	IPR001424,IPR036423	GO:0006801	superoxide metabolic process	ACCEPT	no		Inferred from SOD activity annotation.
RAMVA	RvY_09480	IPR001424,IPR036423	GO:0046872	metal ion binding	KEEP_AS_NON_CORE	yes		Parent term of the more specific Cu/Zn binding annotations. Both Cu and Zn binding are likely.
RAMVA	RvY_10893	IPR024134	GO:0005507	copper ion binding	ACCEPT	no		All four canonical Cu-binding histidines are preserved at the sequence level. Copper binding is likely.
RAMVA	RvY_10893	IPR001424,IPR036423	GO:0006801	superoxide metabolic process	ACCEPT	no		Inferred from SOD activity annotation.
RAMVA	RvY_10893	IPR001424,IPR036423	GO:0046872	metal ion binding	KEEP_AS_NON_CORE	yes		Parent term of the more specific Cu/Zn binding annotations. Both Cu and Zn binding are likely.
RAMVA	RvY_13070	IPR024134	GO:0005507	copper ion binding	ACCEPT	no		Copper binding is confirmed by the crystal structure at 2.1-2.2 A resolution. UniProt lists copper binding residues at positions 85, 104, and 162 with evidence from PMID:37358501 and PDB structures. Although the coordination is atypical (Val87 instead of His), copper is still present in the structure.
RAMVA	RvY_13070	IPR001424,IPR036423	GO:0006801	superoxide metabolic process	MARK_AS_OVER_ANNOTATED	yes		The structural evidence from PMID:37358501 indicates that RvSOD15 has a non-canonical active site (Val87 replacing a catalytic His ligand) and may have evolved to lose SOD function. Without direct evidence of superoxide metabolic activity, this biological process annotation based solely on domain membership is likely an over-annotation.
RAMVA	RvY_13070	IPR001424,IPR036423	GO:0046872	metal ion binding	ACCEPT	no		The term is correct but redundant with more specific annotations. Since this is an IEA and the more specific terms (copper ion binding, zinc ion binding) are already annotated with IDA evidence, this general term adds little informational value but is not incorrect. Accepting as it is a valid broader annotation consistent with the IDA-supported specific terms.
RAMVA	RvY_15948	IPR024134	GO:0005507	copper ion binding	MODIFY	yes	GO:0016532 superoxide dismutase copper chaperone activity	While the annotation is technically correct (CCS does bind copper), the more specific term GO:0016532 (superoxide dismutase copper chaperone activity) better captures the actual biological role of this protein. CCS binds copper specifically for the purpose of transferring it to SOD1.
RAMVA	RvY_15948	IPR001424,IPR036423	GO:0006801	superoxide metabolic process	KEEP_AS_NON_CORE	yes		The protein contributes to superoxide metabolism only indirectly via its role in SOD1 activation. Kept as non-core but a more specific annotation focused on copper homeostasis would be preferable.
RAMVA	RvY_15948	IPR001424,IPR036423	GO:0046872	metal ion binding	KEEP_AS_NON_CORE	yes		Parent term of GO:0005507 (copper ion binding). Redundant with the more specific Cu binding annotation.
RAMVA	RvY_17310	IPR024134	GO:0005507	copper ion binding	ACCEPT	no		All four canonical Cu-binding histidines are preserved at the sequence level. Copper binding is likely.
RAMVA	RvY_17310	IPR001424,IPR036423	GO:0006801	superoxide metabolic process	MARK_AS_OVER_ANNOTATED	yes		Inferred from SOD activity. Same caveats as the MF annotation.
RAMVA	RvY_17310	IPR001424,IPR036423	GO:0046872	metal ion binding	KEEP_AS_NON_CORE	yes		Parent term of the more specific Cu/Zn binding annotations. Both Cu and Zn binding are likely.
RAMVA	SAHS1	IPR000463	GO:0008289	lipid binding	ACCEPT	no		While no direct lipid binding has been experimentally demonstrated for SAHS1, the crystal structure confirms a genuine FABP-like beta-barrel fold with two putative ligand-binding sites that superimpose on those of canonical FABPs (PMID:28703282). The InterPro-based IEA annotation is a reasonable inference from the structural similarity to the FABP family. It is possible that lipid binding is an ancestral function retained or repurposed in SAHS proteins, even though the primary biological role appears to be desiccation protection. The IEA annotation accurately reflects the computational inference and should be retained pending experimental testing.
RHOPA	nirK1	IPR001287,IPR011707	GO:0005507	copper ion binding	ACCEPT	no		nirK1 is annotated as a copper-containing nitrite reductase and has cupredoxin/NO2-reductase_Cu family signatures plus conserved copper-site features. The inference is family/domain based, not direct biochemical evidence in this strain. Falcon found no primary paper characterizing Q6N4N1/RPA3306 directly.
RHOPA	nirK2	IPR001287,IPR011707	GO:0005507	copper ion binding	ACCEPT	no		nirK2 has the same conserved copper nitrite reductase architecture as bacterial NirK enzymes, including NO2-reductase_Cu/cupredoxin signatures and type 1 copper-site features. Falcon recovered RPA4145/nirK2 in comparative NirK literature but no purified nirK2 metal biochemistry.
RHOPA	nosZ	IPR002429	GO:0004129	cytochrome-c oxidase activity	REMOVE	yes	GO:0050304 nitrous-oxide reductase activity	The cytochrome-c oxidase activity term appears to come from a shared cytochrome oxidase subunit II-like copper-binding domain. The protein assignment, EC number, HAMAP model, and PANTHER subfamily all identify this sequence as nitrous-oxide reductase, so GO:0050304 is the correct MF. Family research confirms that PTHR42838 can conflate NosZ with cytochrome c oxidase subunit II because both carry CuA-related domains.
RUMJO	fae1A	IPR002105	GO:0004553	hydrolase activity, hydrolyzing O-glycosyl compounds	ACCEPT	no		The cellulase activity is well-documented and represents a core function of fae1A. The EC number 3.2.1.4 is specifically assigned in UniProt, confirming this enzymatic activity.
RUMJO	fae1A	IPR005084,IPR006584	GO:0030246	carbohydrate binding	ACCEPT	no		The cellulase activity is well-documented and represents a core function of fae1A. The EC number 3.2.1.4 is specifically assigned in UniProt, confirming this enzymatic activity.
SACEN	A4F7M9	IPR007815	GO:0046677	response to antibiotic	ACCEPT	no		Accurate (general) biological process for an erythromycin esterase; retained pending clarification of its physiological role.
SACEN	ermE	IPR020596,IPR020598	GO:0000154	rRNA modification	ACCEPT	no		Accurate (general) biological process; the specific GO:0031167 rRNA methylation is also annotated.
SACEN	eryAI	IPR018201	GO:0004315	3-oxoacyl-[acyl-carrier-protein] synthase activity	MODIFY	yes	GO:0016218 polyketide synthase activity	Wrong-specific (FAS) term for a polyketide ketosynthase domain. Replace with GO:0016218 (polyketide synthase activity).
SACEN	eryAI	IPR001227	GO:0016740	transferase activity	ACCEPT	no		Accurate (general) molecular function.
SACEN	eryAI	IPR016039	GO:0016746	acyltransferase activity	ACCEPT	no		Correct component (AT-domain) molecular function (UniProt Acyltransferase keyword).
SACEN	eryAII	IPR018201	GO:0004315	3-oxoacyl-[acyl-carrier-protein] synthase activity	MODIFY	yes	GO:0016218 polyketide synthase activity	Wrong-specific (FAS) term for a polyketide ketosynthase domain. Replace with GO:0016218.
SACEN	eryAII	IPR020843	GO:0016491	oxidoreductase activity	ACCEPT	no		Correct component (reductive-domain) molecular function.
SACEN	eryAII	IPR001227,IPR015083	GO:0016740	transferase activity	ACCEPT	no		Accurate (general) molecular function.
SACEN	eryAII	IPR016039	GO:0016746	acyltransferase activity	ACCEPT	no		Correct component (AT-domain) molecular function.
SACEN	eryAIII	IPR018201	GO:0004315	3-oxoacyl-[acyl-carrier-protein] synthase activity	MODIFY	yes	GO:0016218 polyketide synthase activity	Wrong-specific (FAS) term for a polyketide ketosynthase domain. Replace with GO:0016218.
SACEN	eryAIII	IPR001227,IPR015083	GO:0016740	transferase activity	ACCEPT	no		Accurate (general) molecular function.
SACEN	eryAIII	IPR016039	GO:0016746	acyltransferase activity	ACCEPT	no		Correct component (AT-domain) molecular function.
SACEN	eryBI	IPR001764,IPR002772,IPR036881,IPR036962	GO:0004553	hydrolase activity, hydrolyzing O-glycosyl compounds	ACCEPT	no		Accurate (general) molecular function.
SACEN	eryBV	IPR002213	GO:0008194	UDP-glycosyltransferase activity	REMOVE	yes		Wrong donor specificity (the donor is TDP-L-mycarose, a dTDP-sugar, not a UDP-sugar). The accurate term GO:0016758 (hexosyltransferase activity) is already present as a separate IEA annotation, so this incorrect UDP-specific term should simply be removed rather than modified into a duplicate.
SACEN	eryBV	IPR030953	GO:0016757	glycosyltransferase activity	ACCEPT	no		Accurate general molecular function.
SACEN	eryBVI	IPR005212	GO:0016829	lyase activity	ACCEPT	no		Correct (general) molecular function consistent with the annotated 2,3-dehydratase role; a more specific dehydratase term would be preferable if available.
SACEN	eryCII	IPR001128,IPR036396	GO:0004497	monooxygenase activity	REMOVE	yes		"Demonstrably incorrect. Beyond the UniProt CAUTION (""lacks the heme-binding sites""), the structure paper shows by structure-based alignment that EryCII lacks the conserved heme-ligating cysteine and is ""not an active P450 enzyme"", and the 2YJN structure is apo (no heme). EryCII functions as a GT activator, not a monooxygenase. Classic domain-propagation over-annotation of a pseudoenzyme."
SACEN	eryCII	IPR001128,IPR036396	GO:0005506	iron ion binding	REMOVE	yes		Incorrect; depends on heme/iron cofactor binding that EryCII has lost. The UniProt CAUTION (lacks the heme-binding sites) and the structure (no heme; absent conserved Cys) agree.
SACEN	eryCII	IPR001128,IPR036396	GO:0016705	oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen	REMOVE	yes		Incorrect catalytic MF for a heme-less, non-catalytic P450 homologue (UniProt CAUTION plus the apo structure / absent conserved Cys).
SACEN	eryCII	IPR001128,IPR036396	GO:0020037	heme binding	REMOVE	yes		"Both the UniProt CAUTION (""lacks the heme-binding sites"") and primary structural data agree: the conserved heme-ligating cysteine is absent and EryCII has ""lost the heme group in the central core"" (PMID:22056329); the 2YJN structure contains no heme ligand. The most clearly incorrect of the inherited P450 terms."
SACEN	eryCIII	IPR002213	GO:0008194	UDP-glycosyltransferase activity	REMOVE	yes		Wrong donor specificity (TDP-D-desosamine, a dTDP-sugar, not a UDP-sugar). The accurate term GO:0016758 (hexosyltransferase activity) is already present (IEA + IDA), so this incorrect UDP-specific term should be removed rather than modified into a duplicate.
SACEN	eryCIII	IPR030953	GO:0016757	glycosyltransferase activity	ACCEPT	no		Accurate general molecular function (true parent of the specific activity).
SACEN	eryCV	IPR007197	GO:0003824	catalytic activity	MARK_AS_OVER_ANNOTATED	yes		Generic catalytic-activity term provides no functional information; a specific MF is preferable.
SACEN	eryCV	IPR016863	GO:0016841	ammonia-lyase activity	UNDECIDED	yes		Conflicting electronic assignments (ammonia-lyase vs 3,4-enoyl reductase) with no accessible experimental characterization; the radical-SAM cofactor binding is, however, well supported.
SACEN	eryCV	IPR016863	GO:0033068	macrolide biosynthetic process	ACCEPT	no		Accurate biological process.
SACEN	eryCV	IPR007197	GO:0051536	iron-sulfur cluster binding	ACCEPT	no		Correct cofactor binding for this radical-SAM-type enzyme.
SACEN	eryCV	IPR016863	GO:0051539	4 iron, 4 sulfur cluster binding	ACCEPT	no		Correct and specific cofactor binding.
SACEN	eryF	IPR001128,IPR002397,IPR036396	GO:0004497	monooxygenase activity	ACCEPT	no		Correct and experimentally supported molecular function.
SACEN	eryF	IPR001128,IPR002397,IPR017972,IPR036396	GO:0005506	iron ion binding	ACCEPT	no		Correct; EryF binds a heme iron, unlike the pseudoenzyme EryCII.
SACEN	eryF	IPR001128,IPR002397,IPR017972,IPR036396	GO:0016705	oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen	ACCEPT	no		Accurate (if general) molecular function.
SACEN	eryF	IPR001128,IPR002397,IPR036396	GO:0020037	heme binding	ACCEPT	no		Correct and experimentally supported.
SACEN	eryK	IPR001128,IPR002397,IPR036396	GO:0004497	monooxygenase activity	ACCEPT	no		Correct and experimentally supported molecular function.
SACEN	eryK	IPR001128,IPR002397,IPR017972,IPR036396	GO:0005506	iron ion binding	ACCEPT	no		Correct; EryK is a heme-iron P450.
SACEN	eryK	IPR001128,IPR002397,IPR017972,IPR036396	GO:0016705	oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen	ACCEPT	no		Accurate (general) molecular function.
SACEN	eryK	IPR001128,IPR002397,IPR036396	GO:0020037	heme binding	ACCEPT	no		Correct and experimentally supported.
SALSP	mcr-4	IPR012549	GO:0016020	membrane	MODIFY	yes	GO:0005886 plasma membrane	Use plasma membrane rather than the generic membrane term where possible.
SALSP	mcr-4	IPR040423	GO:0016772	transferase activity, transferring phosphorus-containing groups	MODIFY	yes	GO:0043838 phosphatidylethanolamine:Kdo2-lipid A phosphoethanolamine transferase activity	Replace the broad or over-specific electronic term 'transferase activity, transferring phosphorus-containing groups' with phosphatidylethanolamine:Kdo2-lipid A phosphoethanolamine transferase activity based on UniProt/CARD determinant identity and the curated ARO->GO mapping.
SCHJY	shc1	IPR018333	GO:0005811	lipid droplet	REMOVE	yes		The IEA annotation likely derives from InterPro domain predictions, but experimental localization data clearly shows Shc1 at membrane sites involved in lipid biosynthesis, not lipid storage organelles. The enzyme functions in membrane lipid production, not storage.
SCHJY	shc1	IPR018333	GO:0016104	triterpenoid biosynthetic process	MODIFY	yes	GO:0019746 hopanoid biosynthetic process	While accurate, GO:0019746 (hopanoid biosynthetic process) is more specific and informative. Hopanoids are a distinct class of triterpenoids with specific biological functions as sterol surrogates.
SCHJY	shc1	IPR006400,IPR018333	GO:0016866	intramolecular transferase activity	ACCEPT	no		This is the correct broad molecular function category for squalene-hopene cyclases. These enzymes catalyze intramolecular rearrangements to form cyclic structures. GO:0051007 (squalene-hopene cyclase activity) is a child term of this category.
SCHPO	aah1	IPR015340	GO:0005509	calcium ion binding	KEEP_AS_NON_CORE	yes		Calcium binding is a conserved structural feature of GH13 enzymes required for proper folding and catalytic activity, but it is not the core function of Aah1. The annotation is likely correct based on domain conservation but represents a cofactor requirement rather than the primary molecular function.
SCHPO	aah1	IPR006047	GO:0005975	carbohydrate metabolic process	MARK_AS_OVER_ANNOTATED	yes		The specific biological processes GO:0070600 (fungal-type cell wall (1->3)-alpha-glucan biosynthetic process) and GO:0051278 (fungal-type cell wall polysaccharide biosynthetic process) are more informative and already present. This broad parent term does not add useful information.
SCHPO	aah1	IPR015340	GO:0016052	carbohydrate catabolic process	REMOVE	yes		Aah1 is not involved in carbohydrate catabolism. It is a transglycosylase that remodels alpha-glucan polymers in the cell wall. No hydrolytic/catabolic activity was detected experimentally, and the protein's biological role is biosynthetic/remodeling rather than degradative.
SCHPO	ago1	IPR003165,IPR036397	GO:0003676	nucleic acid binding	MARK_AS_OVER_ANNOTATED	yes		Uninformatively general; superseded by specific siRNA-binding/ssRNA-binding annotations.
SCHPO	ago1	IPR003100	GO:0003723	RNA binding	MARK_AS_OVER_ANNOTATED	yes		Too general; superseded by specific siRNA/ssRNA binding annotations.
SCHPO	alo1	IPR007173	GO:0016020	membrane	MODIFY	yes	GO:0005741 mitochondrial outer membrane	Too general. Protein specifically localizes to mitochondrial outer membrane based on evidence from orthologs.
SCHPO	alo1	IPR010031	GO:0016899	oxidoreductase activity, acting on the CH-OH group of donors, oxygen as acceptor	KEEP_AS_NON_CORE	yes		Correct but could be more specific. This parent term encompasses the specific activity GO:0003885.
SCHPO	alo1	IPR006094,IPR036318	GO:0050660	flavin adenine dinucleotide binding	ACCEPT	no		Correct annotation. The enzyme contains a conserved FAD-binding domain essential for oxidase activity.
SCHPO	alo1	IPR016166	GO:0071949	FAD binding	REMOVE	yes		Redundant with GO:0050660. Both refer to FAD binding.
SCHPO	ark1	IPR000719,IPR008271,IPR030616	GO:0004672	protein kinase activity	MODIFY	yes	GO:0004674 protein serine/threonine kinase activity	Too general; Ark1 is specifically a Ser/Thr kinase demonstrated experimentally.
SCHPO	ark1	IPR000719,IPR017441	GO:0005524	ATP binding	ACCEPT	no		InterPro inference consistent with the conserved ATP-binding motif and mutagenesis data.
SCHPO	ase1	IPR007145	GO:0000226	microtubule cytoskeleton organization	KEEP_AS_NON_CORE	yes		Accurate but high-level parent term superseded by specific experimental annotations; retain as a non-core general descriptor.
SCHPO	ase1	IPR007145	GO:0008017	microtubule binding	ACCEPT	no		Core MF, corroborated by IDA evidence (PMID:21892183).
SCHPO	atf1	IPR004827,IPR046347	GO:0003700	DNA-binding transcription factor activity	MODIFY	yes	GO:0000981 DNA-binding transcription factor activity, RNA polymerase II-specific	Correct but unnecessarily general; the Pol II-specific child term is appropriate.
SCHPO	atf1	IPR004827,IPR046347	GO:0006355	regulation of DNA-templated transcription	MODIFY	yes	GO:0006357 regulation of transcription by RNA polymerase II	Correct but too general; replace with the RNA polymerase II-specific process term.
SCHPO	atg13	IPR040182	GO:0000045	autophagosome assembly	ACCEPT	no		Autophagosome assembly is a core function of Atg13. The protein is essential for nucleating the autophagy initiation machinery at the PAS and for subsequent autophagosome formation. This IEA annotation is supported by IMP and ISO evidence for macroautophagy in S. pombe.
SCHPO	bst1	IPR012908,IPR039529	GO:0016788	hydrolase activity, acting on ester bonds	MARK_AS_OVER_ANNOTATED	yes		"This InterPro-based annotation accurately captures the chemical mechanism. The deep research explains ""Bst1 catalyzes the hydrolytic removal of this inositol-acyl chain"" involving ""cleavage of the ester bond linking the acyl chain to the inositol ring"" [bst1-deep-research-perplexity.md]. UniProt features include ""ACT_SITE 264"" and the PROSITE pattern ""PS00120 LIPASE_SER"" [bst1-uniprot.txt]. InterPro domains IPR012908 (PGAP1-ab_dom-like) and IPR039529 (PGAP1/BST1) map to this GO term [bst1-uniprot.txt]. However, GO:0016788 lies on the ancestry path to the specific GO:0050185 (phosphatidylinositol deacylase activity), which already captures the ester-bond hydrolase mechanism. For consistency with the MARK_AS_OVER_ANNOTATED decision on the parent term GO:0016787 (hydrolase activity), this intermediate term is likewise over-annotated and superseded by GO:0050185."
SCHPO	bub1	IPR000719	GO:0004672	protein kinase activity	MODIFY	yes	GO:0004674 protein serine/threonine kinase activity	Generic kinase term; the specific serine/threonine kinase term is experimentally supported.
SCHPO	bub1	IPR000719	GO:0005524	ATP binding	ACCEPT	no		Standard and correct for an active protein kinase with a conserved ATP-binding site.
SCHPO	cdc12	IPR010472,IPR010473	GO:0003779	actin binding	ACCEPT	no		InterPro domain-based annotation consistent with experimentally demonstrated actin binding by the FH2 domain.
SCHPO	cdc12	IPR010473	GO:0031267	small GTPase binding	MARK_AS_OVER_ANNOTATED	yes		InterPro domain-only prediction with no experimental support for GTPase binding by cdc12; regulation is via scaffold binding and phosphorylation, not a small GTPase.
SCHPO	cdc13	IPR046965	GO:0044772	mitotic cell cycle phase transition	MODIFY	yes	GO:0010389 regulation of G2/M transition of mitotic cell cycle	The general term is correct but a more specific term reflecting the G2/M role is preferred and is supported experimentally.
SCHPO	cdc18	IPR003959	GO:0005524	ATP binding	ACCEPT	no		InterPro-based ATP-binding inference is consistent with the AAA+ ATPase architecture and the annotated nucleotide-binding P-loop in UniProt.
SCHPO	cdc18	IPR016314	GO:0006270	DNA replication initiation	ACCEPT	no		Correct core function; redundant with the IBA/IMP-supported DNA replication initiation annotations.
SCHPO	cdc18	IPR003959	GO:0016887	ATP hydrolysis activity	ACCEPT	no		Consistent with the AAA+ ATPase architecture; ATP hydrolysis is part of the helicase-loader mechanism, though the in vivo MCM-loading process is the more informative term.
SCHPO	cdc18	IPR016314	GO:0051301	cell division	KEEP_AS_NON_CORE	yes		Broadly true but generic; the specific replication-licensing terms capture the actual function far better.
SCHPO	cdc2	IPR000719,IPR008271	GO:0004672	protein kinase activity	MODIFY	yes	GO:0004693 cyclin-dependent protein serine/threonine kinase activity	Over-general parent; replace with the specific cyclin-dependent ser/thr kinase activity.
SCHPO	cdc2	IPR000719,IPR017441	GO:0005524	ATP binding	ACCEPT	no		Correct supporting molecular function for a protein kinase.
SCHPO	cdc25	IPR000751	GO:1902751	positive regulation of cell cycle G2/M phase transition	MODIFY	yes	GO:0010971 positive regulation of G2/M transition of mitotic cell cycle	The mitotic-specific child term GO:0010971 is preferred over this more general cell cycle phase transition term.
SCHPO	cdc42	IPR001806,IPR037874	GO:0003924	GTPase activity	ACCEPT	no		Core molecular function, supported by InterPro and the GEF/GAP literature.
SCHPO	cdc42	IPR001806,IPR003578,IPR005225	GO:0005525	GTP binding	ACCEPT	no		Core conserved function; supported by sequence motifs and the switch mechanism.
SCHPO	cdc42	IPR003578	GO:0007264	small GTPase-mediated signal transduction	ACCEPT	no		Core conserved process for a Rho-family GTPase; well supported.
SCHPO	cdc7	IPR000719,IPR008271	GO:0004672	protein kinase activity	MODIFY	yes	GO:0004674 protein serine/threonine kinase activity	The InterPro-based parent term is accurate but should be specialized to protein serine/threonine kinase activity, for which there is direct experimental evidence.
SCHPO	cdc7	IPR000719,IPR017441	GO:0005524	ATP binding	ACCEPT	no		Conserved kinase ATP-binding motifs are present and the protein has demonstrated kinase activity, which requires ATP.
SCHPO	cds1	IPR000719,IPR008271	GO:0004672	protein kinase activity	MODIFY	yes	GO:0004674 protein serine/threonine kinase activity	Parent term is correct but too general; the specific Ser/Thr kinase term is directly supported by experiment.
SCHPO	cds1	IPR000719,IPR017441	GO:0005524	ATP binding	ACCEPT	no		ATP binding is an intrinsic property of the kinase domain, supported by sequence features and by the ATP requirement for autoactivation.
SCHPO	chk1	IPR034670	GO:0000077	DNA damage checkpoint signaling	ACCEPT	no		Correct process; the more specific GO:0007095 is preferred for representing the core function but this parent term is not wrong.
SCHPO	chk1	IPR000719,IPR008271	GO:0004672	protein kinase activity	MODIFY	yes	GO:0004674 protein serine/threonine kinase activity	The essence is correct but a more specific child term (protein serine/threonine kinase activity) is experimentally supported and preferred.
SCHPO	chk1	IPR000719,IPR017441	GO:0005524	ATP binding	ACCEPT	no		Supported by the conserved protein kinase domain and ATP-binding motif in the sequence.
SCHPO	clr4	IPR007728	GO:0008270	zinc ion binding	KEEP_AS_NON_CORE	yes		Structurally verified zinc binding required for SET-domain catalysis; supporting rather than core molecular function.
SCHPO	clr4	IPR007728	GO:0042054	histone methyltransferase activity	MARK_AS_OVER_ANNOTATED	yes	GO:0046974 histone H3K9 methyltransferase activity	Over-general parent of the well-supported H3K9-specific methyltransferase activity.
SCHPO	clr4	IPR011381	GO:0046974	histone H3K9 methyltransferase activity	ACCEPT	no		Core molecular function, supported by numerous direct assays.
SCHPO	cmp7	IPR005024	GO:0007034	vacuolar transport	REMOVE	yes		cmp7 is a nuclear-envelope-specific Snf7 family member required for NE integrity and grommet/sealing function at the SPB-extrusion hole. PomBase curators give it no MVB / vacuolar-transport experimental annotations, and the upstream go-annotation tracker (#6458) flags the IPR005024 → vacuolar transport mapping as inappropriate for this gene. The annotation should be removed from cmp7 until the InterPro2GO mapping is revised upstream.
SCHPO	cnp1	IPR000164	GO:0000786	nucleosome	KEEP_AS_NON_CORE	yes		True but a general parent of the more specific CENP-A containing nucleosome term that better captures the function.
SCHPO	cnp1	IPR000164,IPR007125	GO:0003677	DNA binding	MARK_AS_OVER_ANNOTATED	yes		Overly general parent term superseded by nucleosomal DNA binding; provides little functional information for a centromeric histone.
SCHPO	cnp1	IPR000164	GO:0030527	structural constituent of chromatin	ACCEPT	no		Core structural histone function, consistent with the IBA annotation and with experimental data.
SCHPO	cnp1	IPR009072	GO:0046982	protein heterodimerization activity	KEEP_AS_NON_CORE	yes		Histone-fold heterodimerization with H4 underlies nucleosome formation; a supporting molecular activity rather than the core function.
SCHPO	cps1	IPR017141	GO:0004181	metallocarboxypeptidase activity	UNDECIDED	yes		M20 family membership does not definitively indicate carboxypeptidase activity; the family includes aminoacylases with different substrate specificity. Requires experimental validation.
SCHPO	cts2	IPR001223	GO:0005975	carbohydrate metabolic process	KEEP_AS_NON_CORE	yes		The protein may retain some carbohydrate binding or peripheral carbohydrate-metabolic association despite the questionable chitinase activity. This very broad grouping term is plausible from domain membership but is not a definitively supported core function.
SCHPO	cut1	IPR005314,IPR030397	GO:0004197	cysteine-type endopeptidase activity	ACCEPT	no		Correct domain-based inference consistent with the curated EC 3.4.22.49 and experimental protease activity.
SCHPO	cut1	IPR005314,IPR030397	GO:0006508	proteolysis	ACCEPT	no		Correct general process consistent with Cut1's protease activity.
SCHPO	cut2	IPR006940	GO:0005737	cytoplasm	MARK_AS_OVER_ANNOTATED	yes		Experimental evidence places Cut2 in the nucleus/spindle; the cytoplasmic pool is a feature of its partner Cut1, making this an InterPro over-annotation.
SCHPO	cut2	IPR006940	GO:0051276	chromosome organization	MODIFY	yes	GO:2000816 negative regulation of mitotic sister chromatid separation	Overly general parent term; Cut2's documented role is specifically the regulation of mitotic sister chromatid separation/chromosome segregation.
SCHPO	cut7	IPR001752,IPR019821	GO:0005524	ATP binding	ACCEPT	no		Core molecular function supported by domain architecture and biochemical assays.
SCHPO	cut7	IPR001752,IPR019821	GO:0007018	microtubule-based movement	KEEP_AS_NON_CORE	yes		Correct but generic process term; the more specific mitotic spindle terms are the core annotations.
SCHPO	cut7	IPR001752	GO:0008017	microtubule binding	ACCEPT	no		Core molecular function; supported by structural and biochemical IDA evidence.
SCHPO	dcr1	IPR006935	GO:0003677	DNA binding	MARK_AS_OVER_ANNOTATED	yes	GO:0003690 double-stranded DNA binding	Generic DNA binding (InterPro-derived) is less informative than the experimentally supported double-stranded DNA binding term and overstates the role of nucleic acid binding by the dsRBD.
SCHPO	dcr1	IPR000999,IPR036389	GO:0004525	ribonuclease III activity	ACCEPT	no		InterPro2GO inference is correct and corroborated by experimental evidence.
SCHPO	dcr1	IPR006935	GO:0005524	ATP binding	ACCEPT	no		Supported by conserved domain architecture and the identified ATP-binding motif.
SCHPO	dcr1	IPR000999,IPR036389	GO:0006396	RNA processing	MARK_AS_OVER_ANNOTATED	yes	GO:0030422 siRNA processing	Over-general parent term; superseded by siRNA processing (GO:0030422).
SCHPO	dcr1	IPR006935	GO:0016787	hydrolase activity	MARK_AS_OVER_ANNOTATED	yes	GO:0004525 ribonuclease III activity	Subsumed by GO:0004525 ribonuclease III activity.
SCHPO	dcr1	IPR005034	GO:0016891	RNA endonuclease activity producing 5'-phosphomonoesters, hydrolytic mechanism	ACCEPT	no		Mechanistically correct refinement of the catalytic activity, supported by RNase III domain assignment and in vitro cleavage.
SCHPO	gaa1	IPR007246	GO:0016020	membrane	REMOVE	yes		Too generic. The more specific term GO:0005789 (endoplasmic reticulum membrane) is already present and should be used instead.
SCHPO	gaa1	IPR007246	GO:0042765	GPI-anchor transamidase complex	REMOVE	yes		Duplicate of the IBA annotation for the same term. Accept one, remove this duplicate.
SCHPO	gpd3	IPR006424	GO:0006006	glucose metabolic process	KEEP_AS_NON_CORE	yes		Broader term encompassing glycolysis. Valid but less specific than glycolytic process annotations.
SCHPO	gpd3	IPR006424,IPR020829,IPR020830,IPR020831	GO:0016620	oxidoreductase activity, acting on the aldehyde or oxo group of donors, NAD or NADP as acceptor	KEEP_AS_NON_CORE	yes		Correct intermediate term between general oxidoreductase and specific GAPDH activity. Less specific than GO:0004365.
SCHPO	gpd3	IPR006424	GO:0050661	NADP binding	REMOVE	yes		Incorrect annotation. GAPDH uses NAD+, not NADP+. This enzyme is strictly NAD+-dependent, not NADP+-dependent. Likely automated annotation error.
SCHPO	gpd3	IPR006424,IPR020828	GO:0051287	NAD binding	ACCEPT	no		Correct - NAD+ is the required cofactor for GAPDH enzymatic activity. UniProt documents multiple NAD+-binding residues and a Rossmann-fold NAD(P)-binding domain. The enzyme is NAD+-specific (contrast the incorrect NADP-binding annotation, removed above).
SCHPO	mei2	IPR035979	GO:0003676	nucleic acid binding	MARK_AS_OVER_ANNOTATED	yes	GO:0003723 RNA binding	Subsumed by the more specific and experimentally supported molecular function terms RNA binding (GO:0003723) and lncRNA binding (GO:0106222).
SCHPO	mei2	IPR000504	GO:0003723	RNA binding	ACCEPT	no		Mei2 is an RRM-type RNA-binding protein whose RNA-binding activity is essential for its meiotic functions.
SCHPO	mph1	IPR000719,IPR008271	GO:0004672	protein kinase activity	MARK_AS_OVER_ANNOTATED	yes		Correct but redundant generic parent term; the experimentally supported, more specific kinase-activity terms should be preferred.
SCHPO	mph1	IPR000719,IPR017441	GO:0005524	ATP binding	ACCEPT	no		A required molecular function for this active protein kinase, supported by the conserved ATP-binding motif and demonstrated kinase activity.
SCHPO	mus81	IPR006166	GO:0003677	DNA binding	KEEP_AS_NON_CORE	yes		True but generic; subsumed by the more specific crossover junction DNA endonuclease activity.
SCHPO	mus81	IPR033309	GO:0006302	double-strand break repair	ACCEPT	no		Correct, corroborated by IMP evidence (PMID:11719193, PMID:17307401).
SCHPO	mus81	IPR033309	GO:0006308	DNA catabolic process	REMOVE	yes		Over-broad/misleading IEA; Mus81 makes precise resolving incisions in repair/recombination, not DNA degradation. The biology is captured by the recombination and repair BP terms.
SCHPO	pap1	IPR050936	GO:0000976	transcription cis-regulatory region binding	ACCEPT	no		Correct but less specific than experimental GO:0000978.
SCHPO	pap1	IPR004827,IPR046347	GO:0003700	DNA-binding transcription factor activity	ACCEPT	no		Accurate high-level backbone term; more specific experimental terms exist.
SCHPO	pap1	IPR004827,IPR046347	GO:0006355	regulation of DNA-templated transcription	ACCEPT	no		Accurate backbone term; more specific experimental BP exists.
SCHPO	plo1	IPR000719,IPR017441	GO:0005524	ATP binding	ACCEPT	no		Consistent with the conserved protein-kinase ATP-binding site and loss-of-function ATP-pocket mutants.
SCHPO	pmp20	IPR037944	GO:0008379	thioredoxin peroxidase activity	REMOVE	yes		"Pmp20 has been experimentally shown to lack thioredoxin-dependent peroxidase activity. UniProt states ""Has no thioredoxin-dependent peroxidase activity"" and ""Pmp20 lacks the resolving cysteine residue"" (PMID:20356456). The InterPro domain mapping does not account for the absence of the resolving cysteine. The focused OpenScientist hypothesis review independently judged GO:0008379 over-annotated and noted that the organism-wide peroxide-scavenging analysis in PMID:24521463 also supports Tpx1, catalase, and Gpx1 rather than pmp20 as fission yeast peroxide-scavenging activities."
SCHPO	pmp20	IPR037944	GO:0034599	cellular response to oxidative stress	KEEP_AS_NON_CORE	yes		Consistent with the IBA annotation. Pmp20 may have some role in oxidative stress response through its weak chaperone activity, but this is not a core function given the absence of peroxidase activity.
SCHPO	pol5	IPR017964	GO:0000166	nucleotide binding	REMOVE	yes		This annotation appears to be based on weak computational inference from polymerase-like motifs, but pol5 lacks DNA polymerase activity and critical catalytic residues. The term is too general and not supported by functional evidence. Pol5's binding activities are better described by more specific terms like rDNA binding.
SCHPO	pol5	IPR017964	GO:0003676	nucleic acid binding	MODIFY	yes	GO:0000182 rDNA binding; GO:0019843 rRNA binding	Pol5 does bind nucleic acids but this term is too general. The protein specifically binds rDNA and rRNA, so more specific terms like 'rDNA binding' and 'rRNA binding' are more informative and accurate.
SCHPO	pol5	IPR007015	GO:0003677	DNA binding	KEEP_AS_NON_CORE	yes		While technically correct that pol5 binds DNA, this is a very general term. The more specific 'rDNA binding' term better captures pol5's function. This general term can be kept as non-core since it's not incorrect but is less informative than the specific rDNA binding annotation.
SCHPO	pol5	IPR007015	GO:0005730	nucleolus	ACCEPT	no		This is a duplicate annotation with different evidence code but the same GO term. The nucleolar localization is well-established and functionally important for pol5's role in rRNA transcription and ribosome assembly.
SCHPO	pol5	IPR007015	GO:0006355	regulation of DNA-templated transcription	MODIFY	yes	GO:0042254 ribosome biogenesis	This term is too general. Pol5 is best described as a ribosome biogenesis factor that affects rRNA production rather than as a general DNA-templated transcription regulator. To stay consistent with the accepted NOT annotation for GO:0042790 (Pol5 is not a direct Pol I transcription factor), the replacement points to ribosome biogenesis rather than to direct Pol I transcription terms.
SCHPO	pom1	IPR000719,IPR008271	GO:0004672	protein kinase activity	KEEP_AS_NON_CORE	yes		Subsumed by more specific, experimentally supported MF terms.
SCHPO	pom1	IPR000719,IPR017441	GO:0005524	ATP binding	ACCEPT	no		Pom1 has a conserved protein kinase domain with characterized ATP-binding residues; ATP binding is required for its catalytic activity.
SCHPO	ppk34	IPR000719,IPR008271	GO:0004672	protein kinase activity	KEEP_AS_NON_CORE	yes		Redundant with GO:0004674 annotation; less specific.
SCHPO	ppk34	IPR000719	GO:0005524	ATP binding	ACCEPT	no		Appropriate. Ppk34/ckk2 has a canonical protein kinase domain (residues 40-331) with conserved ATP-binding residues (46-54, 69). ATP binding is intrinsic to its kinase activity.
SCHPO	rad21	IPR039781	GO:0007062	sister chromatid cohesion	MODIFY	yes	GO:0007064 mitotic sister chromatid cohesion	The general term is subsumed by the more specific, directly supported mitotic sister chromatid cohesion term.
SCHPO	rad21	IPR039781	GO:0008278	cohesin complex	MODIFY	yes	GO:0030892 mitotic cohesin complex	Subsumed by the more specific mitotic cohesin complex term, which is directly supported.
SCHPO	rad3	IPR018936	GO:0016301	kinase activity	MODIFY	yes	GO:0004674 protein serine/threonine kinase activity	The PIKK signature reflects sequence similarity to lipid kinases, but Rad3 has not been shown to phosphorylate lipids; the informative activity is protein Ser/Thr kinase.
SCHPO	rhp51	IPR010995	GO:0000166	nucleotide binding	MODIFY	yes	GO:0005524 ATP binding	Over-general parent term; replace with the specific ATP binding term.
SCHPO	rhp51	IPR020587,IPR020588	GO:0003677	DNA binding	MARK_AS_OVER_ANNOTATED	yes		Over-general parent term, redundant with more specific ss/dsDNA binding annotations.
SCHPO	rhp51	IPR011941	GO:0003690	double-stranded DNA binding	ACCEPT	no		Correct; redundant with experimental IDA.
SCHPO	rhp51	IPR020587,IPR020588	GO:0005524	ATP binding	ACCEPT	no		Correct; corroborated by experimental IDA and sequence motif.
SCHPO	rhp51	IPR020587	GO:0006259	DNA metabolic process	MARK_AS_OVER_ANNOTATED	yes		Over-general parent of the specific recombination/repair processes already annotated.
SCHPO	rhp51	IPR020588	GO:0006281	DNA repair	KEEP_AS_NON_CORE	yes		Correct but general parent; specific repair terms preferred.
SCHPO	rhp51	IPR011941,IPR020587	GO:0008094	ATP-dependent activity, acting on DNA	ACCEPT	no		Correct core activity; redundant with IDA.
SCHPO	rhp51	IPR020588	GO:0140664	ATP-dependent DNA damage sensor activity	MARK_AS_OVER_ANNOTATED	yes		Likely InterPro over-propagation; the documented activity is recombinase, not damage sensing.
SCHPO	rhp51	IPR011941	GO:1990426	mitotic recombination-dependent replication fork processing	ACCEPT	no		Correct; redundant with experimental IMP.
SCHPO	rqh1	IPR010997	GO:0000166	nucleotide binding	MODIFY	yes	GO:0005524 ATP binding	Too general; ATP binding is the specific, experimentally supported MF for this RecQ helicase and is already present.
SCHPO	rqh1	IPR002121,IPR011545	GO:0003676	nucleic acid binding	MODIFY	yes	GO:0003677 DNA binding	Too general; DNA binding is the specific supported molecular function.
SCHPO	rqh1	IPR004589	GO:0004386	helicase activity	MODIFY	yes	GO:0043138 3'-5' DNA helicase activity	Too general; biochemical data establish 3'-5' DNA helicase activity (GO:0043138), which is already annotated experimentally.
SCHPO	rqh1	IPR011545	GO:0005524	ATP binding	ACCEPT	no		Supported by the conserved ATP-binding motif and the demonstrated ATP-dependent helicase activity.
SCHPO	rqh1	IPR018982	GO:0006260	DNA replication	KEEP_AS_NON_CORE	yes		Generic term; replication-associated role is better captured by replication fork processing terms.
SCHPO	rqh1	IPR018982	GO:0006281	DNA repair	KEEP_AS_NON_CORE	yes		Correct but general parent term; specific DSB-repair-via-HR and fork processing terms better represent the core function.
SCHPO	rqh1	IPR004589	GO:0006310	DNA recombination	KEEP_AS_NON_CORE	yes		Correct but general parent; specific terms (resolution of recombination intermediates, recombinational repair) capture the core role.
SCHPO	scm3	IPR018465	GO:0042393	histone binding	KEEP_AS_NON_CORE	yes		Scm3 specifically binds the CENP-A histone variant Cnp1 via its N-terminal domain (PMID:19217403). The same yeast two-hybrid experiment detected no Scm3-H4 interaction; it did not establish an equivalent negative result for H3. Histone binding is correct but less informative than histone chaperone activity (GO:0140713).
SCHPO	scm3	IPR009072	GO:0046982	protein heterodimerization activity	MARK_AS_OVER_ANNOTATED	yes		Likely derived from the InterPro histone-fold domain annotation. While Scm3 does interact with Cnp1/CENP-A and self-associates (PMID:19217403), its mechanism of action is as a histone chaperone, not as a classical histone-fold heterodimerization partner. The S. pombe Scm3 is not an integral nucleosome component. This annotation is misleading.
SCHPO	sgo1	IPR011515	GO:0045132	meiotic chromosome segregation	KEEP_AS_NON_CORE	yes		Accurate but high-level InterPro-based parent of the experimentally supported specific meiotic terms.
SCHPO	sid2	IPR000719,IPR008271	GO:0004672	protein kinase activity	MODIFY	yes	GO:0004674 protein serine/threonine kinase activity	Redundant general parent; the specific protein serine/threonine kinase activity term should be used.
SCHPO	sid2	IPR000719,IPR000961,IPR017441,IPR017892	GO:0005524	ATP binding	ACCEPT	no		Conserved kinase ATP-binding site; supported by mutational analysis of the ATP-binding lysine.
SCHPO	slp1	IPR033010	GO:0010997	anaphase-promoting complex binding	ACCEPT	no		InterPro Cdc20/Fizzy signature maps appropriately to APC/C binding; concordant with experimental evidence.
SCHPO	slp1	IPR033010	GO:0097027	ubiquitin-protein transferase activator activity	MODIFY	yes	GO:1990757 ubiquitin ligase activator activity	"The APC/C is a RING E3 ubiquitin ligase; ""ubiquitin ligase activator activity"" (GO:1990757) is the more precise and experimentally supported term for Slp1's coactivator role."
SCHPO	snx41	IPR001683,IPR036871,IPR044106	GO:0035091	phosphatidylinositol binding	ACCEPT	no		This is a valid molecular function annotation. SNX41 specifically binds PI3P, which is a type of phosphatidylinositol. More specific annotations for PI3P binding (GO:0032266) are available via IBA, but this term is not incorrect as a parent term.
SCHPO	snx41	IPR044106	GO:0042147	retrograde transport, endosome to Golgi	ACCEPT	no		This biological process annotation is core to SNX41 function. The Snx4-Snx41 heterodimer mediates retrograde transport of specific cargo proteins like Atg27 from post-Golgi endosomes back to the trans-Golgi network. Falcon deep research places Snx41-family proteins at the intersection of endosomal retrograde trafficking and autophagy/protein homeostasis.
SCHPO	sty1	IPR000719,IPR008271	GO:0004672	protein kinase activity	MARK_AS_OVER_ANNOTATED	yes	GO:0004707 MAP kinase activity	Subsumed by the more specific and experimentally supported MAP kinase activity annotation; the bare parent term adds little.
SCHPO	sty1	IPR000719,IPR003527,IPR008352,IPR017441	GO:0005524	ATP binding	ACCEPT	no		Standard, well-supported kinase cofactor/substrate binding.
SCHPO	sty1	IPR038783	GO:0051403	stress-activated MAPK cascade	ACCEPT	no		Corroborates the core stress-activated MAPK cascade function (InterPro-based computational call consistent with the IBA annotation).
SCHPO	tpx1	IPR019479	GO:0051920	peroxiredoxin activity	ACCEPT	no		Supported by InterPro/family inference and corroborated by falcon deep research.
SCHPO	ura7	IPR033828	GO:0006241	CTP biosynthetic process	ACCEPT	no		IEA annotation based on InterPro domain analysis correctly identifies the CTP biosynthetic function. This is accurate and represents the primary biological role of the enzyme.
SCHPO	wee1	IPR000719,IPR008271	GO:0004672	protein kinase activity	ACCEPT	no		Correct parent term; the specific protein tyrosine kinase and serine/threonine kinase activities better capture the function.
SCHPO	wee1	IPR000719,IPR017441	GO:0005524	ATP binding	ACCEPT	no		Accurate and functionally validated ATP-binding activity required for catalysis.
SCHPO	wis1	IPR000719,IPR008271	GO:0004672	protein kinase activity	MARK_AS_OVER_ANNOTATED	yes	GO:0004708 MAP kinase kinase activity	Correct but uninformatively general; the specific MAP kinase kinase activity term is supported and preferred.
SCHPO	wis1	IPR000719,IPR017441	GO:0005524	ATP binding	ACCEPT	no		ATP binding is an expected, sequence- and structure-supported feature of the active kinase domain.
SEPOF	RHO	IPR000276	GO:0004930	G protein-coupled receptor activity	ACCEPT	no		This is a core molecular function of rhodopsin. As a 7-transmembrane rhabdomeric opsin, it couples to Gq-alpha to initiate the invertebrate phototransduction cascade. The InterPro domain match (IPR000276) and CDD classification (cd15337, 7tmA_Opsin_Gq_invertebrates) unambiguously place this protein in the GPCR superfamily. Experimental evidence from related cephalopods confirms Gq-alpha coupling (PMID:25994635). Biochemical studies in squid demonstrated that light-activated rhodopsin catalyzes GTP binding to a 42 kDa Gq protein, and a ~130 kDa PLC was purified and shown to be activated by Gq (PMID:1445212, PMID:9636052).
SEPOF	RHO	IPR000276,IPR001760	GO:0007186	G protein-coupled receptor signaling pathway	MODIFY	yes	GO:0030265 phospholipase C-activating opsin-mediated signaling pathway	GO:0030265 (phospholipase C-activating opsin-mediated signaling pathway) is a child of both GPCR signaling (GO:0007186) and phototransduction (GO:0007602), capturing both aspects in a single specific term. Its definition explicitly describes the Gq-PLC-PIP2 rhabdomeric cascade used by protostome photoreceptors including cephalopods.
SEPOF	RHO	IPR001760	GO:0007601	visual perception	ACCEPT	no		"Visual perception is a core biological process for rhodopsin in the retina. The gene was cloned from retinal cDNA (PMID:9662500), and UniProt annotates it as required for ""image-forming vision at low light intensity."" S. officinalis is monochromatic with a single retinal rhodopsin (lambda-max ~492 nm), but compensates for color-blindness through polarization sensitivity conferred by the orthogonal microvillar arrangement in rhabdomeric photoreceptors (PMID:20392722). This annotation only captures the ocular function -- the dermal/extraocular photoreception role is not covered and is proposed as a NEW annotation below."
SEPOF	RHO	IPR000276,IPR001760,IPR017452	GO:0016020	membrane	KEEP_AS_NON_CORE	yes		This is a correct but generic cellular component annotation. As a 7TM receptor, rhodopsin is by definition an integral membrane protein. However, the more specific annotations (plasma membrane, rhabdomere membrane) are more informative. This IEA annotation is redundant with the more specific ISS annotations below, but is not incorrect.
SOLLC	DET1	IPR008928	GO:0005975	carbohydrate metabolic process	REMOVE	yes		"This annotation is a false-positive driven by remote structural similarity, not function. The InterPro signature IPR008928 is the ""six-hairpin glycosidase-like"" superfamily FOLD (SSF48208), which DET1 shares only at the level of overall fold architecture (the De-etiolated_protein_1_Det1 family, IPR019138/PF09737, is the function-relevant signature) [file:SOLLC/DET1/DET1-uniprot.txt]. DET1 is a nuclear ubiquitin-ligase adaptor and photomorphogenesis repressor with no glycoside-hydrolase or carbohydrate-metabolic activity in any of the experimental literature [file:SOLLC/DET1/DET1-deep-research-falcon.md]. Mapping a structural superfamily to ""carbohydrate metabolic process"" is an over-annotation and should be removed."
SOLLC	PG2	IPR000743	GO:0005975	carbohydrate metabolic process	MARK_AS_OVER_ANNOTATED	yes		"""Carbohydrate metabolic process"" is a very high-level grouping term. PG2 does metabolize a carbohydrate polymer (pectin / homogalacturonan), so the term is not incorrect, but it conveys almost none of the gene's actual biology. The specific, informative biological process is pectin catabolic process (GO:0045490), proposed as a NEW term below and directly supported by the in-vitro hydrolysis of pectic polymers [PMID:9701584] and by the antisense/in-vivo depolymerization evidence [PMID:7827495]. Once the specific pectin-catabolism term is present, the broad carbohydrate-metabolism parent adds no information and is best regarded as an over-annotation."
SOLLC	PR1B1	IPR018244	GO:0005576	extracellular region	ACCEPT	no		Well supported. The signal peptide and the established apoplastic localization of tomato PR-1 proteins make extracellular region the correct compartment. PR-1 biology, including CAPE1 release and sterol sequestration from apoplastic pathogens, occurs in the extracellular space. The IBA annotation in UniProt (GO:0005615 extracellular space) is fully consistent and more specific; the broader extracellular region term is also correct.
SOLTU	CCOAOMT	IPR002935	GO:0008171	O-methyltransferase activity	MODIFY	yes	GO:0042409 caffeoyl-CoA O-methyltransferase activity	"CCoAOMT is genuinely an O-methyltransferase, so the term is not wrong, but it is a broad parent of the gene's precise, EC-backed molecular function. The protein ""catalyzes O-methylation of ... caffeoyl-CoA to feruloyl-CoA"" and is assigned EC 2.1.1.104 / Rhea:16925, so the specific child term ""caffeoyl-CoA O-methyltransferase activity"" (GO:0042409) - already present in current GOA - is the informative MF. The generic O-methyltransferase term should be modified (deepened) to the specific caffeoyl-CoA O-methyltransferase activity rather than retained as a free-standing high-level annotation."
SOLTU	JOKA2	IPR000433	GO:0008270	zinc ion binding	KEEP_AS_NON_CORE	yes		"The ZZ-type zinc finger is a genuine structural feature inferred by InterPro and present in the UniProt feature table (ZN_FING 442-492, ""ZZ-type; degenerate""; BINDING residues for Zn(2+)), so zinc binding is plausible. In NBR1-family receptors the ZZ domain participates in cargo recognition rather than catalysis. However, the domain is explicitly degenerate in JOKA2, there is no gene-specific experimental evidence for metal binding, and zinc binding is a structural/auxiliary property rather than the protein's core selective-autophagy-receptor function. Retain as a correct but non-core molecular feature."
SOLTU	PATB1	IPR002641	GO:0006629	lipid metabolic process	MODIFY	yes	GO:0016042 lipid catabolic process	"Patatin is a lipid acyl hydrolase: its activity is deacylation/breakdown of glycerolipids (release of free fatty acids and lysolipids), which is lipid CATABOLISM rather than generic lipid metabolism. The deep research describes patatin LAH activity as releasing fatty acids from polar and neutral glycerolipids, and UniProt assigns the keywords ""Lipid degradation"" and ""Lipid metabolism"". The hydrolytic, degradative direction is well established, so the more specific child term ""lipid catabolic process"" (GO:0016042) is the accurate process annotation - and it is exactly the term that the retired SPKW annotation (re-added below) used. Modifying the generic IEA up to the catabolic child consolidates the process annotation at the correct specificity."
SORBI	SORBI_3003G204000	IPR044951	GO:0051983	regulation of chromosome segregation	ACCEPT	no		"The family assignment is well supported: the entry carries InterPro IPR044951 (SPC24-like) and PANTHER PTHR35730, whose single reviewed member is the Arabidopsis SPC24 homolog (Q67XT3, gene SPC24/MUN). The experimentally characterized plant ortholog MUN is a functional SPC24 subunit of the NDC80 kinetochore complex required for proper chromosome segregation [PMID:29356153], and the partner subunit NUF2 likewise governs chromosome segregation in plant mitosis [PMID:33993566]. The annotated direction (involvement in chromosome segregation) is therefore correct, and as a conservative, curated InterPro2GO inference applied electronically to an organism with no direct experimental data it should be retained. Critically, however, this single IEA mapping is incomplete: it captures a biological-process term but omits the most characteristic feature of an SPC24 protein — its localization as a structural subunit of the NDC80 complex at the kinetochore. Those defining cellular-component annotations (GO:0031262 NDC80 complex; GO:0000776 kinetochore) are added below as orthology-based (ISS) NEW annotations rather than left implicit. The IEA term ""regulation of chromosome segregation"" itself is a defensible parent-level statement (the NDC80 complex both executes microtubule attachment and contributes to spindle-checkpoint regulation of the metaphase-to-anaphase transition), so it is accepted as-is rather than modified."
SOYBN	PPC16	IPR021135,IPR022805	GO:0006099	tricarboxylic acid cycle	MODIFY	yes	GO:0006107 oxaloacetate metabolic process	The TCA cycle (GO:0006099) is defined as the cyclic oxidation of acetyl-CoA via citrate, isocitrate, 2-oxoglutarate, succinyl-CoA, succinate, fumarate, malate and oxaloacetate. PEPC catalyses none of these steps; it is the canonical ANAPLEROTIC enzyme that replenishes TCA-cycle C4 intermediates consumed by biosynthesis and N assimilation. Annotating PEPC as involved_in the TCA cycle is too coarse and asserts cycle membership it does not have. A biologically accurate replacement is oxaloacetate metabolic process (GO:0006107), which captures PEPC's role in producing the OAA that feeds the cycle without asserting that the protein is part of the cycle.
SOYBN	PPC16	IPR021135,IPR022805	GO:0015977	carbon fixation	MODIFY	yes	GO:0006107 oxaloacetate metabolic process	GO:0015977 (carbon fixation) is defined as a metabolic process in which carbon (usually from CO2) is incorporated into organic compounds, usually carbohydrates; every child term is an autotrophic, net-carbon-gain pathway. Housekeeping PEPC carboxylates PEP to oxaloacetate for anaplerosis; it does not produce carbohydrate and does not perform autotrophic carbon fixation. As with the retired photosynthesis annotation, this is a family-level keyword/InterPro over-annotation: the carbon-fixing role of PEPC belongs to the dedicated C4/CAM photosynthetic isozymes, not to the C3 housekeeping isozyme. The biologically accurate process term is oxaloacetate metabolic process (GO:0006107), reflecting the anaplerotic carboxylation that produces OAA.
SPHSM	tetX	IPR043683	GO:0046677	response to antibiotic	ACCEPT	no		The response/resistance annotation is biologically sound, but the core value for this review is the missing precise molecular-function term.
SPHSM	tetX	IPR002938,IPR043683	GO:0071949	FAD binding	KEEP_AS_NON_CORE	yes		FAD binding is mechanistically relevant but secondary to the catalytic antibiotic-inactivation activity.
STAAU	ant	IPR002934	GO:0016779	nucleotidyltransferase activity	MODIFY	yes	GO:0034068 aminoglycoside nucleotidyltransferase activity	Replace the broad or over-specific electronic term 'nucleotidyltransferase activity' with aminoglycoside nucleotidyltransferase activity based on UniProt/CARD determinant identity and the curated ARO->GO mapping.
STAAU	ant	IPR024172	GO:0046677	response to antibiotic	ACCEPT	no		The CARD/ARO determinant identity supports an antibiotic-resistance biological role.
STAAU	ant	IPR024172	GO:0070566	adenylyltransferase activity	MODIFY	yes	GO:0034068 aminoglycoside nucleotidyltransferase activity	Replace the broad or over-specific electronic term 'adenylyltransferase activity' with aminoglycoside nucleotidyltransferase activity based on UniProt/CARD determinant identity and the curated ARO->GO mapping.
STABO	mdr	IPR003439,IPR017871	GO:0016887	ATP hydrolysis activity	ACCEPT	no		The mechanistic description of ABC pumps supports ATP hydrolysis for SbSLMdr.1. [PMID:34998388]
STABO	mdr	IPR011527	GO:0055085	transmembrane transport	ACCEPT	no		Direct evidence for sophorolipid export supports transmembrane transport. [PMID:34998388, PMID:23516968]
STABO	mdr	IPR011527	GO:0140359	ABC-type transporter activity	ACCEPT	no		ABC-family classification for SbSLMdr.1 supports ABC-type transporter activity. [PMID:34998388]
STAWA	cfr	IPR007197	GO:0003824	catalytic activity	MARK_AS_OVER_ANNOTATED	yes		The specific Cfr activity is radical-SAM 23S rRNA A2503 C8 methyltransferase activity. Generic catalytic activity should not be the retained molecular-function representation where better terms exist.
STAWA	cfr	IPR004383	GO:0006364	rRNA processing	MODIFY	yes	GO:0070475 rRNA base methylation	Cfr performs a base methylation on mature 23S rRNA. GO:0070475 is the better process-level representation than generic rRNA processing.
STAWA	cfr	IPR005839	GO:0006400	tRNA modification	REMOVE	yes		The Cfr record and Cfr mechanism literature identify 23S rRNA A2503 as the substrate. This review found no support that Cfr modifies tRNA.
STAWA	cfr	IPR004383	GO:0008173	RNA methyltransferase activity	MODIFY	yes	GO:0016433 rRNA (adenine) methyltransferase activity	Cfr is an rRNA adenine methyltransferase, not a generic RNA methyltransferase. GO still lacks the exact C8/A2503 child term.
STAWA	cfr	IPR005839	GO:0016740	transferase activity	MODIFY	yes	GO:0016433 rRNA (adenine) methyltransferase activity	Generic transferase activity is a weak representation of Cfr compared with GO:0016433.
STAWA	cfr	IPR007197	GO:0051536	iron-sulfur cluster binding	MODIFY	yes	GO:0051539 4 iron, 4 sulfur cluster binding	Replace broad iron-sulfur cluster binding with the specific 4Fe-4S cluster binding annotation for Cfr.
STRCO	actI-ORF1	IPR018201	GO:0006633	fatty acid biosynthetic process	MODIFY	yes	GO:1901112 actinorhodin biosynthetic process	Wrong biological process. Replace with the specific, accurate term GO:1901112 (actinorhodin biosynthetic process).
STRCO	actI-ORF1	IPR016039	GO:0016746	acyltransferase activity	ACCEPT	no		Correct general molecular function (true parent of polyketide synthase activity); retained as accurate but non-specific.
STRCO	actI-ORF2	IPR016039	GO:0016746	acyltransferase activity	MARK_AS_OVER_ANNOTATED	yes		Attributes a catalytic MF to a non-catalytic subunit. CLF contributes_to (is required for) the KS-CLF activity and sets chain length, but does not itself catalyze acyl transfer; the activity should be annotated to the type II PKS complex with a contributes_to qualifier.
STRCO	fusB	IPR000795	GO:0003924	GTPase activity	UNDECIDED	yes		The structural GTPase domain is present, but functional GTPase activity is questionable. EF-G2 paralogs in Bacteroides [PMID:36472247] and Mycobacterium [PMID:40569974] lack ribosome-dependent GTPase activity. Whether S. coelicolor fusB retains any GTPase activity (intrinsic or ribosome-stimulated) has not been experimentally determined. The annotation may be technically correct at the structural level but functionally misleading.
STRCO	lexA	IPR006197	GO:0006355	regulation of DNA-templated transcription	KEEP_AS_NON_CORE	yes		While accurate, this is a general term. The more specific negative regulation of DNA-templated transcription (GO:0045892) better captures LexA function as a repressor.
STRCO	lexA	IPR006199	GO:0006508	proteolysis	KEEP_AS_NON_CORE	yes		Accurate but general term. LexA performs autocatalytic cleavage (self-proteolysis) which is more specifically captured by the serine-type endopeptidase activity annotation.
THLAR	CYP71B1	IPR001128,IPR002401,IPR036396	GO:0004497	monooxygenase activity	ACCEPT	no		Well-supported family-level inference. The protein has canonical cytochrome P450 domain architecture (Pfam PF00067), and plant P450s are heme-thiolate monooxygenases. The specific substrate and reaction are unknown, but monooxygenase activity is a sound conservative annotation.
THLAR	CYP71B1	IPR001128,IPR002401,IPR017972,IPR036396	GO:0005506	iron ion binding	ACCEPT	no		Correct. The P450 catalytic center binds an iron-containing heme; UniProt annotates an axial heme iron-binding residue at position 436. Iron ion binding is appropriate, captured more specifically by the heme binding annotation.
THLAR	CYP71B1	IPR001128,IPR002401,IPR017972,IPR036396	GO:0016705	oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen	ACCEPT	no		Correct and standard for a cytochrome P450 monooxygenase, which uses molecular oxygen with NADPH as the paired electron donor. Conservative family-level inference.
THLAR	CYP71B1	IPR001128,IPR002401,IPR036396	GO:0020037	heme binding	ACCEPT	no		Correct. Cytochrome P450s are heme-thiolate proteins; UniProt annotates the axial heme iron-binding residue (position 436). This is the most specific cofactor annotation and underpins the monooxygenase activity.
THLAR	matK	IPR002866,IPR024937	GO:0006397	mRNA processing	ACCEPT	no		Acceptable. Several MatK splicing targets are group IIA introns within protein-coding (mRNA) transcripts, including atpF, rpl2 and rps12, so MatK does contribute to mRNA processing. The more precise activity is captured by the group II intron splicing annotation below.
VIBPA	priB	IPR023646	GO:0006260	DNA replication	MODIFY	yes	GO:0031297 replication fork processing	"PriB does not participate in origin-dependent replication initiation or general replication elongation. Its role is specifically in the PriA-dependent replication restart pathway, which reloads the replicative helicase at stalled or abandoned forks. GO:0031297 (replication fork processing), defined as ""the process in which a DNA replication fork that has stalled is restored to a functional state and replication is restarted"", is the appropriate specific term. The broad term GO:0006260 is not wrong per se but is insufficiently specific."
VIBPA	priB	IPR023646	GO:0030894	replisome	REMOVE	yes		"PriB is explicitly described in the literature and UniProt as a component of the replication restart primosome, not the replisome. The replisome is the complex that actively replicates DNA (including polymerase, helicase, primase), while the primosome is a transient assembly that reloads the helicase at stalled forks. UniProt states PriB is a ""Component of the replication restart primosome"" and the correct CC term GO:1990077 (primosome complex) is already annotated and accepted in a separate GOA row. Modifying this annotation to GO:1990077 would create a duplicate; the over-broad InterPro-based replisome mapping from IPR023646 should be removed."
VITVI	STS3	IPR016039,IPR018088	GO:0016746	acyltransferase activity	MARK_AS_OVER_ANNOTATED	yes		"GO:0016746 ""acyltransferase activity"" is a correct but very high-level grandparent of the precise activity. STS3 has a specifically defined, experimentally characterized activity (trihydroxystilbene synthase activity, GO:0050350, EC 2.3.1.95) that is also annotated on this protein. The broad parent term adds no information beyond the precise term and is an over-annotation relative to what is known. It is not wrong, so it is marked as over-annotated rather than removed; the precise child term GO:0050350 should be retained as the representative MF."
VITVI	STS3	IPR011141	GO:0016747	acyltransferase activity, transferring groups other than amino-acyl groups	MARK_AS_OVER_ANNOTATED	yes		GO:0016747 is correct (STS3 transfers a malonyl/acyl group, not an amino-acyl group) and is the immediate parent of the precise term GO:0050350, which is also annotated on this protein. Because the precise child term fully captures the activity and EC 2.3.1.95, this broad parent is redundant and represents an over-annotation in terms of specificity. Marked as over-annotated rather than removed because it is taxonomically/biochemically accurate; GO:0050350 should be retained as the core MF.
WHEAT	A0A3B6GK97	IPR002641	GO:0006629	lipid metabolic process	ACCEPT	no		"The protein contains a well-defined PNPLA/patatin domain (PROSITE PS51635, residues 1-134; SUPFAM SSF52151; Gene3D 3.40.1090.10), and the patatin family is a family of lipid acyl hydrolases acting on glycerolipids. ""Lipid metabolic process"" is the correct, appropriately general BP given that only a domain match (not substrate-resolved experimental data) is available. The IEA evidence and InterPro2GO provenance are sound. (Caveat - in-repo bioinformatics shows the deposited model lacks the catalytic serine and may be a truncated gene model; the lipid-metabolic role is therefore a family/subfamily-level inference rather than confirmed for this sequence. Lipid metabolic process is deliberately retained as the substrate- and direction-neutral umbrella and is NOT sharpened to lipid catabolic process, since an acyl hydrolase may act in remodeling or signaling rather than degradation.)"
WHEAT	A0A3B6NKR6	IPR006204	GO:0005524	ATP binding	KEEP_AS_NON_CORE	yes		ATP binding is a cofactor interaction intrinsic to kinase activity rather than the defining molecular function of this protein. The more informative annotation would be glucuronokinase activity (GO:0047940), which subsumes the ATP-binding aspect. Keeping as non-core since it is technically correct but not the primary functional descriptor.
XANCP	Q8P365	IPR000889	GO:0004601	peroxidase activity	MODIFY	yes	GO:0004602 glutathione peroxidase activity	InterPro maps IPR000889 (Glutathione_peroxidase) to the general peroxidase activity term GO:0004601. However, the protein is specifically classified in the glutathione peroxidase family with the GSHPx Pfam domain (PF00255) and the GPX active site motif (IPR029759). The more specific term GO:0004602 (glutathione peroxidase activity) better reflects the predicted enzymatic function. This is a standard InterPro2GO mapping limitation where the mapping is broader than the family assignment warrants.
XANCP	Q8P365	IPR000889	GO:0006979	response to oxidative stress	KEEP_AS_NON_CORE	yes		GO:0006979 (response to oxidative stress) is an ancestor of GO:0034599 (cellular response to oxidative stress). The IBA annotation to the more specific child term already captures the biology. Retaining this broader IEA annotation is not incorrect but adds no new information; it is kept as non-core.
XENTR	A0A8J1IYX6	IPR008271	GO:0004672	protein kinase activity	MARK_AS_OVER_ANNOTATED	yes		Redundant with the more specific GO:0004674 protein serine/threonine kinase activity annotation that is already present. PKCdelta is specifically a serine/threonine kinase, not a tyrosine kinase.
XENTR	F6WPT1	IPR006689	GO:0003924	GTPase activity	ACCEPT	no		GTPase activity is a core molecular function of ARL5A. As an ARF-family GTPase, the protein hydrolyzes GTP as part of its regulatory cycle. The InterPro domain assignment (IPR006689, Small_GTPase_ARF/SAR) is correct, and the P-loop NTPase fold with conserved catalytic residues supports GTPase activity. This is distinct from but complementary to the GTP binding annotation -- together they describe the complete GTPase cycle.
XENTR	F6WPT1	IPR005225,IPR006689,IPR024156	GO:0005525	GTP binding	ACCEPT	no		GTP binding is a fundamental function of ARL5A confirmed by multiple independent domain annotations. While redundant with the IBA annotation for the same GO term, the InterPro evidence provides independent computational support. The domain architecture (Arf domain, P-loop NTPase fold) is fully consistent with GTP binding activity.
XENTR	aldh1a2	IPR016163	GO:0016620	oxidoreductase activity, acting on the aldehyde or oxo group of donors, NAD or NADP as acceptor	REMOVE	yes		While this annotation is correct, it's too general compared to the more specific GO:0001758 (retinal dehydrogenase activity) which better describes the enzyme's substrate specificity.
human	AARSD1	IPR018163	GO:0000166	nucleotide binding	REMOVE	yes		No convincing evidence for a standalone nucleotide-binding function of canonical AARSD1.
human	AARSD1	IPR018165	GO:0003676	nucleic acid binding	MARK_AS_OVER_ANNOTATED	yes		Substrate binding is implicit in the catalytic proofreading activity; generic nucleic acid binding is too broad for this gene.
human	AARSD1	IPR012947	GO:0004812	aminoacyl-tRNA ligase activity	REMOVE	yes		Incorrect molecular-function assignment for canonical AARSD1.
human	AARSD1	IPR018165	GO:0004813	alanine-tRNA ligase activity	REMOVE	yes		Not supported for canonical AARSD1; this annotation conflates editing with aminoacylation.
human	AARSD1	IPR012947,IPR018165	GO:0005524	ATP binding	REMOVE	yes		Likely a false positive carried over from aaRS homology rather than an authentic activity of AARSD1.
human	AARSD1	IPR018165	GO:0006419	alanyl-tRNA aminoacylation	REMOVE	yes		AARSD1 maintains fidelity after aminoacylation rather than catalyzing alanine charging.
human	AARSD1	IPR012947	GO:0043039	tRNA aminoacylation	REMOVE	yes		Canonical AARSD1 is a trans-editing factor, not an aminoacyl-tRNA synthetase.
human	ABCB7	IPR011527,IPR036640	GO:0016020	membrane	ACCEPT	no		While accurate, this is a very general term. GO:0005743 (mitochondrial inner membrane) is more appropriate and already annotated. Keeping as valid but non-core.
human	ABCB7	IPR003439,IPR017871	GO:0016887	ATP hydrolysis activity	ACCEPT	no		ATP hydrolysis activity is experimentally validated. The E433K disease mutation impairs ATP hydrolysis stimulation and cluster transport.
human	ABCB7	IPR011527	GO:0055085	transmembrane transport	ACCEPT	no		Accurate general annotation. Already covered by more specific Fe-S cluster transport annotation.
human	ABCB7	IPR011527	GO:0140359	ABC-type transporter activity	ACCEPT	no		ABCB7 is a member of the ABC transporter superfamily, ABCB family. The annotation is accurate.
human	ABCD3	IPR005283	GO:0005324	long-chain fatty acid transmembrane transporter activity	ACCEPT	no		Correct IEA annotation consistent with IBA and experimental annotations for same term.
human	ABCD3	IPR005283	GO:0015910	long-chain fatty acid import into peroxisome	ACCEPT	no		Consistent with experimental annotations.
human	ABCD3	IPR005283,IPR011527,IPR036640	GO:0016020	membrane	ACCEPT	no		Correct but very general. Acceptable as a broad IEA annotation alongside more specific peroxisomal membrane annotations.
human	ABCD3	IPR003439,IPR017871	GO:0016887	ATP hydrolysis activity	ACCEPT	no		Consistent with experimental annotations.
human	ABCD3	IPR005283	GO:0042626	ATPase-coupled transmembrane transporter activity	ACCEPT	no		Consistent with IDA annotation for same term.
human	ABCD3	IPR011527	GO:0055085	transmembrane transport	ACCEPT	no		Correct but general. More specific transport process terms are also annotated.
human	ABCD3	IPR011527	GO:0140359	ABC-type transporter activity	ACCEPT	no		Correct classification. ABCD3 belongs to the ABC transporter superfamily, ABCD family.
human	ABCE1	IPR003439,IPR017871	GO:0005524	ATP binding	ACCEPT	no		ATP binding is a required component of ABCE1's ATP hydrolysis-driven ribosome recycling mechanism.
human	ABCE1	IPR003439,IPR017871	GO:0016887	ATP hydrolysis activity	ACCEPT	no		ATP hydrolysis is the core molecular activity that powers ABCE1-mediated ribosome splitting.
human	ABCF2	IPR003439,IPR017871	GO:0005524	ATP binding	ACCEPT	no		The domain architecture supports ATP binding. The annotation is generic but appropriate for ABCF2's molecular-function model.
human	ABCF2	IPR003439,IPR017871	GO:0016887	ATP hydrolysis activity	ACCEPT	no		ATP hydrolysis activity is the most informative existing molecular function term for ABCF2. The biological process coupled to this ATPase activity remains uncertain; the ribosome-associated quality-control projection was not accepted without direct ABCF2 evidence.
human	ABTB2	IPR009072	GO:0046982	protein heterodimerization activity	MARK_AS_OVER_ANNOTATED	yes		Retain the domain context but do not treat generic heterodimerization as a core function. The direct ABTB2 literature supports a more informative substrate-adaptor-like role in TRAP1 ubiquitination-dependent degradation, captured below as GO:1990756.
human	ABTB3	IPR009072	GO:0046982	protein heterodimerization activity	MARK_AS_OVER_ANNOTATED	yes		The histone-fold architecture may support protein-protein interaction potential, but this broad InterPro transfer is less informative than the directly supported PDZ domain binding annotation. The 2023 Btbd11 study maps the PSD-95 interaction to a C-terminal PDZ-binding motif, not to a demonstrated histone-fold heterodimerization mechanism.
human	ACAD9	IPR006089	GO:0003995	acyl-CoA dehydrogenase activity	ACCEPT	no		The InterPro-based IEA annotation is correct and consistent with experimental data showing ACAD9 possesses acyl-CoA dehydrogenase activity (PMID:16020546, PMID:34646991). This is a broader annotation that is subsumed by the IBA and IDA annotations but not incorrect.
human	ACAD9	IPR006091,IPR009075,IPR009100,IPR013786,IPR036250,IPR037069,IPR046373	GO:0016627	oxidoreductase activity, acting on the CH-CH group of donors	ACCEPT	no		The acyl-CoA dehydrogenase reaction catalyzed by ACAD9 involves oxidation of the CH-CH bond at the alpha-beta position of fatty acyl-CoA substrates. This InterPro-derived term is accurate and at an appropriate level of specificity for automated annotation.
human	ACAD9	IPR013786,IPR037069	GO:0050660	flavin adenine dinucleotide binding	ACCEPT	no		ACAD9 binds FAD as a cofactor for its acyl-CoA dehydrogenase activity. The FAD content of purified ACAD9 is approximately 70% (PMID:34646991), and ECSIT-mediated deflavination switches ACAD9 from FAO enzyme to CI assembly factor (PMID:33320993).
human	ACIN1	IPR035979	GO:0003676	nucleic acid binding	MODIFY	yes	GO:0003723 RNA binding	The specific supported molecular function is RNA binding in the ASAP/EJC splicing context, not generic nucleic acid binding.
human	ADRB2	IPR000276	GO:0004930	G protein-coupled receptor activity	MODIFY	yes	GO:0004941 beta2-adrenergic receptor activity	Replace the broad GPCR activity term with the more specific beta2-adrenergic receptor activity already supported for ADRB2.
human	ADRB2	IPR002233	GO:0004935	adrenergic receptor activity	MODIFY	yes	GO:0004941 beta2-adrenergic receptor activity	ADRB2 is specifically the beta-2 adrenergic receptor, so the specific child term should be used rather than a broader adrenergic receptor activity term.
human	ADRB2	IPR000332	GO:0006940	regulation of smooth muscle contraction	MARK_AS_OVER_ANNOTATED	yes		The previous MARCH2 citation was introductory background rather than experimental support. Because the cached evidence directly supports ADRB2 receptor signaling and trafficking rather than smooth-muscle contraction regulation, this broad IEA physiology row should be treated as over-annotated.
human	ADRB2	IPR000276,IPR002233	GO:0007186	G protein-coupled receptor signaling pathway	MODIFY	yes	GO:0071875 adrenergic receptor signaling pathway; GO:0071880 adenylate cyclase-activating adrenergic receptor signaling pathway	Replace the broad GPCR signaling pathway with adrenergic receptor signaling and, where appropriate, the adenylate cyclase-activating adrenergic receptor signaling pathway.
human	ADRB2	IPR000332	GO:0007189	adenylate cyclase-activating G protein-coupled receptor signaling pathway	MODIFY	yes	GO:0071880 adenylate cyclase-activating adrenergic receptor signaling pathway	Use the adrenergic receptor-specific adenylate cyclase-activating pathway term for ADRB2 rather than the generic GPCR parent.
human	ADRB2	IPR000332	GO:0097746	blood vessel diameter maintenance	MARK_AS_OVER_ANNOTATED	yes		The previous MARCH2 citation was introductory background rather than experimental support. The reviewed evidence supports catecholamine receptor signaling, but not a direct ADRB2-specific blood-vessel-diameter maintenance assay, so this IEA row is over-annotated.
human	AFG3L2	IPR000642,IPR005936,IPR011546,IPR037219	GO:0004176	ATP-dependent peptidase activity	ACCEPT	no		The m-AAA protease uses ATP hydrolysis to unfold/translocate substrates and protease active sites to degrade them.
human	AFG3L2	IPR000642,IPR005936,IPR011546,IPR037219	GO:0004222	metalloendopeptidase activity	ACCEPT	no		Direct structural and biochemical studies support AFG3L2 as a zinc metalloprotease that cleaves substrates after ATP-driven translocation.
human	AFG3L2	IPR000642,IPR003959,IPR003960,IPR011546,IPR037219	GO:0005524	ATP binding	KEEP_AS_NON_CORE	yes		Keep as a non-core molecular feature; core function should emphasize ATP hydrolysis and ATP-dependent peptidase activity.
human	AFG3L2	IPR011546	GO:0008270	zinc ion binding	KEEP_AS_NON_CORE	yes		Keep as a cofactor/domain feature and emphasize metalloendopeptidase activity as the core molecular function.
human	AFG3L2	IPR005936,IPR011546	GO:0016020	membrane	MODIFY	yes	GO:0005743 mitochondrial inner membrane	AFG3L2 is specifically an integral mitochondrial inner membrane protein.
human	AGK	IPR001206	GO:0016301	kinase activity	MODIFY	yes	GO:0047620 acylglycerol kinase activity; GO:0004143 ATP-dependent diacylglycerol kinase activity	AGK is a lipid kinase, and the existing review contains the more informative acylglycerol and diacylglycerol kinase terms. The generic kinase term should be replaced by these specific activities.
human	AGO1	IPR003165,IPR036397	GO:0003676	nucleic acid binding	MARK_AS_OVER_ANNOTATED	yes		The informative molecular function is Argonaute small-RNA/miRNA binding within RISC rather than a broad nucleic-acid or RNA-binding label.
human	AGO2	IPR003165,IPR036397	GO:0003676	nucleic acid binding	MARK_AS_OVER_ANNOTATED	yes		The informative molecular function is Argonaute small-RNA/miRNA binding within RISC rather than a broad nucleic-acid or RNA-binding label.
human	AGO2	IPR028602	GO:0006355	regulation of DNA-templated transcription	KEEP_AS_NON_CORE	yes		Argonaute paralogs have reported nuclear/regulatory interactions, but the dominant conserved function remains small-RNA-guided post-transcriptional repression.
human	AGO2	IPR028602	GO:0070551	endoribonuclease activity, cleaving siRNA-paired mRNA	ACCEPT	no		AGO2 is the principal human slicer Argonaute and cleaves guide-complementary target RNA in RISC.
human	AGO3	IPR003165,IPR036397	GO:0003676	nucleic acid binding	MARK_AS_OVER_ANNOTATED	yes		The informative molecular function is Argonaute small-RNA/miRNA binding within RISC rather than a broad nucleic-acid or RNA-binding label.
human	AGO3	IPR028603	GO:0031047	regulatory ncRNA-mediated gene silencing	ACCEPT	no		The falcon report supports AGO3 function in miRISC-mediated small-RNA-guided repression and related RISC complexes or cytoplasmic RNP compartments.
human	AGO3	IPR028603	GO:0072091	regulation of stem cell proliferation	KEEP_AS_NON_CORE	yes		This process may be supported in a particular experiment or pathway model, but it is peripheral to the core Argonaute/RISC molecular role.
human	AGO4	IPR003165,IPR036397	GO:0003676	nucleic acid binding	MARK_AS_OVER_ANNOTATED	yes		The informative molecular function is Argonaute small-RNA/miRNA binding within RISC rather than a broad nucleic-acid or RNA-binding label.
human	AGRN	IPR001881	GO:0005509	calcium ion binding	ACCEPT	no		Calcium binding is a documented and functionally important molecular activity of agrin. The calcium-induced conformational change in the z8-containing neural isoforms is essential for full biological activity at NMJ. This is mechanistically important.
human	AHR	IPR013767	GO:0006355	regulation of DNA-templated transcription	ACCEPT	no		Transcriptional regulation is the central biological output of activated AHR. The term is broad in some cases, but the direction and process are supported by ligand-induced target gene activation and by cofactor/transactivation-domain evidence.
human	AHR	IPR039091	GO:0006805	xenobiotic metabolic process	ACCEPT	no		AHR does not enzymatically metabolize xenobiotics itself, but GO biological-process annotations correctly capture its upstream receptor/transcription-factor role in xenobiotic response and metabolism programs.
human	AHR	IPR011598,IPR036638	GO:0046983	protein dimerization activity	MODIFY	yes	GO:0046982 protein heterodimerization activity	The biologically relevant dimer for activated AHR is AHR:ARNT. Existing human evidence specifically supports heterodimerization, so the generic dimerization annotation should be refined.
human	AHSA1	IPR015310	GO:0001671	ATPase activator activity	ACCEPT	no		The InterPro-to-GO mapping is correct. The AHSA1 N-terminal domain (Aha1_N, Pfam PF09229) is the domain responsible for binding the HSP90 middle domain and stimulating ATPase activity (PMID:12604615). This IEA annotation is redundant with the IBA and IDA annotations but correctly captures the function.
human	AHSA1	IPR015310	GO:0051087	protein-folding chaperone binding	ACCEPT	no		AHSA1 is a well-established HSP90-binding co-chaperone. The InterPro-to-GO mapping correctly captures the chaperone binding function. This is supported by multiple experimental studies (PMID:12504007, PMID:12604615, PMID:27353360, PMID:29127155).
human	AIP	IPR001179,IPR046357	GO:0003755	peptidyl-prolyl cis-trans isomerase activity	REMOVE	yes		AIP contains an FKBP-type PPIase-like domain that is catalytically inactive (PMID:19375531). The InterPro domain match is structurally correct but the functional annotation of PPIase activity is incorrect for this protein. This is a well-documented case of a domain homolog that has lost enzymatic activity. Therefore the PN peptidyl-prolyl isomerase projection should not be propagated for AIP.
human	AIPL1	IPR046357	GO:0003755	peptidyl-prolyl cis-trans isomerase activity	REMOVE	yes		AIPL1 should not be annotated as a peptidyl-prolyl cis-trans isomerase solely from its FKBP-like domain. Gene-specific evidence indicates lack of FK506 binding and lack of peptidylprolylisomerase activity, so the computational FKBP/PPIase transfer is an overcall.
human	AIRE	IPR000770,IPR008087	GO:0003677	DNA binding	MODIFY	yes	GO:0000977 RNA polymerase II transcription regulatory region sequence-specific DNA binding	Generic DNA binding is less informative than the existing RNA polymerase II transcription regulatory region sequence-specific DNA binding annotation.
human	AIRE	IPR008087	GO:0006959	humoral immune response	MARK_AS_OVER_ANNOTATED	yes		The literature supports self-tolerance and autoimmune phenotypes, not a direct AIRE role in humoral immune effector response. Keep this as an over-annotation rather than a core AIRE function.
human	AIRE	IPR008087	GO:0045182	translation regulator activity	REMOVE	yes		No curated AIRE evidence supports direct translation regulator activity. The better-supported molecular functions are histone binding, chromatin binding, sequence-specific DNA binding, and transcriptional regulation.
human	ANG	IPR001427	GO:0003676	nucleic acid binding	MARK_AS_OVER_ANNOTATED	yes		Generic nucleic acid binding does not describe the catalytic RNA-cleavage function.
human	ANKFY1	IPR000306	GO:0046872	metal ion binding	MODIFY	yes	GO:1901981 phosphatidylinositol phosphate binding	The FYVE domain is biologically important because it binds PI3P-containing membranes; direct lipid-binding experiments support phosphatidylinositol phosphate binding, while generic metal ion binding is not informative for ANKFY1 function.
human	AP1B1	IPR002553,IPR008152,IPR009028,IPR013037,IPR015151	GO:0006886	intracellular protein transport	ACCEPT	no		Core function of AP-1. The complex recognizes sorting signals on cargo proteins and mediates their transport between TGN and endosomes. This is a direct consequence of AP-1's adaptor function.
human	AP1B1	IPR002553,IPR008152,IPR009028,IPR013037,IPR015151,IPR026739	GO:0016192	vesicle-mediated transport	ACCEPT	no		Core function, same as IBA annotation above. The IEA annotation from InterPro domains provides independent computational support for this core function.
human	AP1B1	IPR002553,IPR009028	GO:0030117	membrane coat	MODIFY	yes	GO:0030121 AP-1 adaptor complex	While membrane coat is accurate, the more specific term GO:0030121 (AP-1 adaptor complex) better describes the actual complex that AP1B1 is part of. The beta1 subunit is a structural component of the AP-1 heterotetrameric complex.
human	AP1B1	IPR015151	GO:0030131	clathrin adaptor complex	MODIFY	yes	GO:0030121 AP-1 adaptor complex	Accurate but can be made more specific. The specific complex is AP-1 (GO:0030121), which is a child term of clathrin adaptor complex.
human	AP1B1	IPR016342	GO:0030276	clathrin binding	ACCEPT	no		Core molecular function. Beta-adaptins are known to directly bind clathrin through their hinge region, recruiting clathrin to form coated vesicles. This is a fundamental property of the beta1 subunit.
human	AP3B1	IPR002553,IPR015151	GO:0006886	intracellular protein transport	ACCEPT	no		This is consistent with the established role of AP-3 in sorting proteins. The InterPro domains (IPR002553, IPR015151) correctly associate with this transport function.
human	AP3B1	IPR002553,IPR015151,IPR026739,IPR026740	GO:0016192	vesicle-mediated transport	ACCEPT	no		This annotation via InterPro mapping correctly captures the vesicle transport function of AP-3 adaptor complexes. Having both IBA and IEA evidence is acceptable.
human	AP3B1	IPR002553	GO:0030117	membrane coat	ACCEPT	no		AP-3 is indeed a component of the membrane coat, functioning like other adaptor complexes to form vesicle coats.
human	AP3B1	IPR026740	GO:0030123	AP-3 adaptor complex	ACCEPT	no		This is the defining cellular component annotation for AP3B1. Multiple studies confirm AP3B1 as the beta-3A subunit of AP-3.
human	AP3B1	IPR015151	GO:0030131	clathrin adaptor complex	ACCEPT	no		While there is evidence for clathrin-independent AP-3 function in some contexts, the complex does bind clathrin via the beta3 subunit. This annotation is broadly correct.
human	AP3B2	IPR002553	GO:0006886	intracellular protein transport	ACCEPT	no		This annotation accurately reflects AP-3 function. AP-3 complexes mediate the recruitment of clathrin to membranes and recognition of sorting signals in cargo proteins for intracellular transport to lysosomes and lysosome-related organelles.
human	AP3B2	IPR002553,IPR026739,IPR026740	GO:0016192	vesicle-mediated transport	ACCEPT	no		Same term as IBA annotation above; both are valid annotations from different evidence sources. The IEA annotation correctly infers vesicle-mediated transport function from the conserved adaptor protein domains.
human	AP3B2	IPR002553	GO:0030117	membrane coat	ACCEPT	no		AP-3 functions as a membrane coat protein complex. The beta3 subunit contains domains characteristic of coat proteins including the clathrin/coatomer adaptor-like N-terminal domain. The original beta-NAP paper explicitly describes it as a vesicle coat protein.
human	AP3B2	IPR026740	GO:0030123	AP-3 adaptor complex	ACCEPT	no		This is a core annotation for AP3B2. The protein is definitionally a component of the AP-3 adaptor complex, serving as one of the four subunits (delta, beta, mu, sigma) of the heterotetrameric complex. UniProt and all structural/functional studies confirm this.
human	AP4B1	IPR002553,IPR015151	GO:0006886	intracellular protein transport	ACCEPT	no		Intracellular protein transport is a well-supported function of AP-4. The complex sorts cargo proteins including ATG9A from TGN to endosomes. This is an appropriate level of specificity for an IEA annotation.
human	AP4B1	IPR002553,IPR015151,IPR026739	GO:0016192	vesicle-mediated transport	ACCEPT	no		This is the same term as the IBA annotation but with IEA evidence from InterPro. Both annotations are valid - the IEA provides domain-based evidence while IBA provides phylogenetic evidence. Vesicle-mediated transport is a well-established core function.
human	AP4B1	IPR002553	GO:0030117	membrane coat	ACCEPT	no		AP-4 functions as a membrane coat complex on TGN-derived vesicles. The beta4 subunit is an integral component of this coat.
human	AP4B1	IPR015151	GO:0030131	clathrin adaptor complex	REMOVE	yes		"This annotation is incorrect and should be removed. AP-4 forms a non-clathrin coat and does not function as a clathrin adaptor complex. The GO term GO:0030124 (AP-4 adaptor complex) definition itself states ""it is not clear whether AP-4 forms clathrin coats in vivo."" Multiple primary sources explicitly describe AP-4 as non-clathrin-associated. The InterPro domain mapping is too broad and fails to capture this critical distinction."
human	AP4B1	IPR016342	GO:0030276	clathrin binding	REMOVE	yes		This annotation should be removed. AP-4 is a clathrin-independent adaptor complex and there is no evidence that AP4B1 binds clathrin. The InterPro domain family (IPR016342) includes beta subunits from multiple adaptor complexes, but AP-4 specifically is clathrin-independent.
human	APBB1	IPR039576	GO:0001540	amyloid-beta binding	ACCEPT	no		This IEA annotation correctly captures the APP-binding function of Fe65 based on InterPro domain analysis. The PTB domains in Fe65 are recognized as APP-binding domains. Consistent with the IBA annotation.
human	APLP1	IPR011178,IPR036669	GO:0046914	transition metal ion binding	KEEP_AS_NON_CORE	yes		Zinc and copper are transition metals; UniProt notes binding in the extracellular domain.
human	APP	IPR011178,IPR036669	GO:0046914	transition metal ion binding	ACCEPT	no		Core function of APP. Well documented.
human	ARCN1	IPR027059	GO:0006890	retrograde vesicle-mediated transport, Golgi to endoplasmic reticulum	ACCEPT	no		This annotation is correct and represents ARCN1's primary biological process function. Although it duplicates the IBA annotation with GO:0006890, having multiple lines of evidence (IBA and IEA from InterPro) is acceptable and reinforces the annotation. The InterPro domain IPR027059 (Coatomer delta subunit) correctly maps to retrograde transport function.
human	ARCN1	IPR027059	GO:0030126	COPI vesicle coat	ACCEPT	no		This annotation is correct and represents ARCN1's core cellular component identity. The InterPro domain IPR027059 (Coatomer delta subunit) correctly maps to COPI vesicle coat. While this duplicates the IBA annotation, having multiple evidence codes strengthens the annotation confidence. ARCN1 is definitively a core structural component of the COPI coat.
human	AREL1	IPR000569,IPR035983	GO:0004842	ubiquitin-protein transferase activity	MODIFY	yes	GO:0061630 ubiquitin protein ligase activity	GO:0061630 captures the specific ubiquitin protein ligase activity of AREL1.
human	ARF1	IPR006689,IPR045872	GO:0003924	GTPase activity	ACCEPT	no		The GTP/GDP cycle is the core molecular function of ARF1. GTP binding promotes membrane/effector engagement and GTP hydrolysis, stimulated by ARFGAPs and coatomer, drives coat disassembly.
human	ARIH1	IPR031127	GO:0004842	ubiquitin-protein transferase activity	ACCEPT	no		ubiquitin-protein transferase activity is a core ARIH1 function: ARIH1/HHARI is an RBR E3 that transfers ubiquitin from an E2 enzyme through its catalytic cysteine to substrates.
human	ARIH1	IPR002867	GO:0008270	zinc ion binding	ACCEPT	no		ARIH1 contains RING/IBR/RING zinc-finger domains required for its RBR E3 mechanism, so zinc ion binding is supported.
human	ARIH1	IPR018957	GO:0046872	metal ion binding	MODIFY	yes	GO:0008270 zinc ion binding	Specific zinc-binding domains are known; the generic metal ion binding term is less informative.
human	ARL6	IPR006689,IPR041839	GO:0003924	GTPase activity	ACCEPT	no		Consistent with the Arf-family GTPase identity (UniProt; PDB 2H57). The Q73L hydrolysis-deficient variant studies confirm a hydrolyzable GTPase. Core MF.
human	ARL6	IPR005225,IPR006689,IPR024156	GO:0005525	GTP binding	ACCEPT	no		Core molecular function, independently supported by structure and biochemistry.
human	ARL8A	IPR006689,IPR044154	GO:0003924	GTPase activity	ACCEPT	no		ARL8A is a small GTPase that cycles between GDP-bound and GTP-bound states, and structural/biochemical literature supports nucleotide-bound ARL8 family function. The NAS/IEA evidence is broad but biologically correct for this protein family.
human	ARL8A	IPR005225,IPR006689,IPR044154	GO:0005525	GTP binding	ACCEPT	no		ARL8A is a small GTPase that cycles between GDP-bound and GTP-bound states, and structural/biochemical literature supports nucleotide-bound ARL8 family function. The NAS/IEA evidence is broad but biologically correct for this protein family.
human	ARL8A	IPR044154	GO:0015031	protein transport	MODIFY	yes	GO:0032418 lysosome localization	ARL8A regulates lysosome/endolysosome positioning and movement along microtubules rather than protein transport as a generic cargo class. The better process-level assertion is lysosome localization, which captures the positioning/motility role without implying direct protein-cargo transport.
human	ARL8B	IPR006689,IPR044154	GO:0003924	GTPase activity	ACCEPT	no		GTP binding/hydrolysis and small G-protein switching are core molecular features of ARL8B that underlie effector recruitment on endolysosomal membranes.
human	ARL8B	IPR005225,IPR006689,IPR044154	GO:0005525	GTP binding	ACCEPT	no		GTP binding/hydrolysis and small G-protein switching are core molecular features of ARL8B that underlie effector recruitment on endolysosomal membranes.
human	ARL8B	IPR044154	GO:0015031	protein transport	MARK_AS_OVER_ANNOTATED	yes		ARL8B evidence supports lysosome positioning and specific late-endosome/phagosome/autophagosome-to-lysosome traffic rather than generic protein transport; the more specific lysosome localization and late endosome-to-lysosome transport annotations are already present and accepted.
human	ARNT	IPR011598,IPR036638	GO:0046983	protein dimerization activity	MODIFY	yes	GO:0046982 protein heterodimerization activity	ARNT primarily functions by heterodimerizing with AHR, HIF1A/EPAS1, and other bHLH-PAS partners. The broad dimerization term loses the biologically important partner-specific heterodimer context.
human	ASCC1	IPR004088,IPR036612	GO:0003723	RNA binding	MARK_AS_OVER_ANNOTATED	yes		The strongest ASCC alkylation-damage papers show RNA dependence of ASCC foci and direct ssRNA binding by ASCC3, while the earlier ASCC1 paper only described a putative RNA-binding motif. A later structural study (PMID:38750793) now provides direct EMSA evidence that ASCC1 binds sequence-selectively to CGCG-containing RNA via its KH GXXG motif, so ASCC1 RNA binding is a genuine molecular activity. It is retained as non-core here because the physiological endogenous RNA targets remain undefined and the in-cell functional contribution of ASCC1 RNA binding to transcription/repair is not yet established; the action is unchanged pending that evidence.
human	ASCC2	IPR003892	GO:0043130	ubiquitin binding	MODIFY	yes	GO:0070530 K63-linked polyubiquitin modification-dependent protein binding	ASCC2 binds K63-linked polyubiquitin through its CUE domain in both the DNA repair and hRQT literature; the narrower K63-linked polyubiquitin-dependent binding term should be used.
human	ASCC3	IPR011545	GO:0003676	nucleic acid binding	MODIFY	yes	GO:0043138 3'-5' DNA helicase activity	ASCC3 is a nucleic-acid-dependent ATPase/helicase, but the InterPro-derived term is too general. Direct evidence supports 3'-5' DNA helicase activity in ALKBH3-mediated repair.
human	ASCC3	IPR011545	GO:0005524	ATP binding	KEEP_AS_NON_CORE	yes		ASCC3 uses ATP-dependent helicase activity in both DNA repair and hRQT ribosome splitting. ATP binding is true as a supporting property, but ATP hydrolysis activity and the specific biological processes carry the core functional meaning.
human	ASCL1	IPR015660	GO:0006357	regulation of transcription by RNA polymerase II	ACCEPT	no		This is a core function of ASCL1. It regulates transcription both positively (neuronal genes) and negatively (e.g., PACE4 gene). The IEA annotation is appropriate.
human	ASCL1	IPR011598,IPR036638	GO:0046983	protein dimerization activity	ACCEPT	no		Dimerization is essential for ASCL1 function. It heterodimerizes with E-proteins to bind DNA. UniProt documents interactions with TCF3 and TCF4 with multiple experiments.
human	ATAD1	IPR003959,IPR003960	GO:0005524	ATP binding	KEEP_AS_NON_CORE	yes		ATP binding is accurate but less informative than ATP hydrolysis activity and membrane protein dislocase activity, which capture the functional mechanism.
human	ATAD3A	IPR003959	GO:0005524	ATP binding	ACCEPT	no		ATP binding is an intrinsic molecular feature of the ATAD3A AAA+ ATPase domain and supports the core ATP hydrolysis activity.
human	ATAD3A	IPR003959	GO:0016887	ATP hydrolysis activity	ACCEPT	no		The catalytic ATPase activity is a core molecular function of ATAD3A.
human	ATF2	IPR004827,IPR046347	GO:0003700	DNA-binding transcription factor activity	ACCEPT	no		Correct but less specific than GO:0000981. Acceptable as broader IEA.
human	ATF2	IPR004827,IPR046347	GO:0006355	regulation of DNA-templated transcription	ACCEPT	no		Correct but general. Acceptable as broader IEA alongside more specific terms.
human	ATF3	IPR000837,IPR004827,IPR046347	GO:0003700	DNA-binding transcription factor activity	MODIFY	yes	GO:0000981 DNA-binding transcription factor activity, RNA polymerase II-specific	ATF3 is a nuclear bZIP RNA polymerase II transcription factor with sequence-specific cis-regulatory DNA binding. The current broad term is true but less informative than the more specific ATF3 terms already supported by IBA, UniProt, and primary literature.
human	ATF3	IPR000837	GO:0006357	regulation of transcription by RNA polymerase II	ACCEPT	no		This biological process captures ATF3 core activity at a suitable level, because ATF3 can repress or activate target transcription depending on dimerization state, isoform, promoter, and cellular context.
human	ATF4	IPR004827,IPR046347	GO:0006355	regulation of DNA-templated transcription	ACCEPT	no		Consistent with ATF4's established role as a transcriptional regulator.
human	ATG2A	IPR026849	GO:0006914	autophagy	MODIFY	yes	GO:0000045 autophagosome assembly	ATG2A is not merely associated with generic autophagy; direct experiments support a more specific role in autophagosome assembly through phagophore expansion and lipid transfer.
human	ATG2B	IPR026849	GO:0006914	autophagy	MODIFY	yes	GO:0000045 autophagosome assembly	Modify to GO:0000045 autophagosome assembly. ATG2B is not merely associated with autophagy in general; it is required for formation and closure/expansion of autophagosomal membranes.
human	ATG4D	IPR046792	GO:0019786	protein-phosphatidylethanolamide deconjugating activity	ACCEPT	no		Core molecular function. This IEA annotation is redundant with the IBA annotation but both correctly capture ATG4D's delipidation activity, which is its predominant function in cells.
human	ATG7	IPR035985	GO:0008641	ubiquitin-like modifier activating enzyme activity	ACCEPT	no		Core molecular function category. ATG7 is an E1-like ubiquitin-activating enzyme for ATG12 and ATG8. More specific terms (GO:0019778, GO:0019779) better capture the specificity.
human	ATL3	IPR003191,IPR015894,IPR030386,IPR036543	GO:0005525	GTP binding	ACCEPT	no		ATL3 nucleotide binding is directly coupled to GTP hydrolysis, dimerization, and fusion.
human	ATP13A1	IPR023299	GO:0000166	nucleotide binding	MODIFY	yes	GO:0005524 ATP binding	Use the specific ATP-binding term already present in GOA.
human	ATP13A1	IPR001757	GO:0005524	ATP binding	ACCEPT	no		ATP binding is required for the catalytic cycle underlying ATP13A1 dislocase activity.
human	ATP13A1	IPR001757,IPR006544	GO:0016020	membrane	MODIFY	yes	GO:0005789 endoplasmic reticulum membrane	Replace broad membrane localization with ER membrane.
human	ATP13A1	IPR001757	GO:0016887	ATP hydrolysis activity	ACCEPT	no		ATP hydrolysis powers the conformational cycle used for TM extraction.
human	ATP13A1	IPR006544	GO:0140358	P-type transmembrane transporter activity	MODIFY	yes	GO:0140567 membrane protein dislocase activity	Use membrane protein dislocase activity for the actual physiological substrate class.
human	ATP23	IPR019165	GO:0004222	metalloendopeptidase activity	ACCEPT	no		Accept as core molecular function. Human ATP23 has the Peptidase_M76_ATP23 InterPro/Pfam signatures and conserved metal-binding/catalytic features; yeast mutagenesis shows that the HEXXH active-site glutamate is required for cleavage of the Atp6 precursor.
human	ATP5F1A	IPR000793,IPR005294	GO:0015986	proton motive force-driven ATP synthesis	ACCEPT	no		Correct and consistent with the IBA annotation. Proton motive force-driven ATP synthesis is the core biological process of Complex V. Duplicate evidence from IEA is acceptable.
human	ATP5F1A	IPR033732	GO:0032559	adenyl ribonucleotide binding	ACCEPT	no		Correct but broad. The alpha subunit binds adenyl ribonucleotides (ATP and ADP) at its non-catalytic sites. More specific terms (GO:0005524 ATP binding, GO:0043531 ADP binding) are already annotated. As an IEA this broader term is acceptable.
human	ATP5F1A	IPR004100,IPR036121	GO:0046034	ATP metabolic process	ACCEPT	no		Correct but very general. ATP5F1A is involved in ATP metabolism (primarily synthesis as part of Complex V, but the complex can also hydrolyze ATP). More specific annotations for ATP biosynthetic process and proton motive force-driven ATP synthesis are present.
human	ATP5F1B	IPR005722	GO:0015986	proton motive force-driven ATP synthesis	ACCEPT	no		Correct. This broader term subsumes GO:0042776. Redundant with the IBA and IDA annotations for the same term, but as an IEA it is perfectly acceptable. ATP5F1B is a core component of the proton motive force-driven ATP synthesis machinery.
human	ATP5F1B	IPR004100,IPR036121	GO:0046034	ATP metabolic process	ACCEPT	no		Correct but very general. ATP5F1B is involved in ATP metabolism (primarily synthesis, but the complex can also hydrolyze ATP). More specific annotations for ATP biosynthetic process and proton motive force-driven ATP synthesis are present.
human	ATP5IF1	IPR007648	GO:0042030	ATPase inhibitor activity	ACCEPT	no		The InterPro-based electronic annotation correctly identifies the core molecular function. The ATPase_inhibitor_mt domain (IPR007648) is directly associated with ATPase inhibitor activity, and this is the primary function of IF1 supported by extensive experimental evidence.
human	ATP5MC1	IPR000454,IPR002379	GO:0015078	proton transmembrane transporter activity	ACCEPT	no		This is a core molecular function accurately describing the proton translocation activity.
human	ATP5MC1	IPR000454	GO:0015986	proton motive force-driven ATP synthesis	ACCEPT	no		Core biological process, well-supported by domain annotation.
human	ATP5MC1	IPR002379	GO:0033177	proton-transporting two-sector ATPase complex, proton-transporting domain	ACCEPT	no		Accurate specific component annotation. The c-ring is the central rotor of the F₀ domain.
human	ATP5MC2	IPR000454,IPR002379	GO:0015078	proton transmembrane transporter activity	ACCEPT	no		Core molecular function.
human	ATP5MC2	IPR000454	GO:0015986	proton motive force-driven ATP synthesis	ACCEPT	no		Primary biological process function.
human	ATP5MC2	IPR002379	GO:0033177	proton-transporting two-sector ATPase complex, proton-transporting domain	ACCEPT	no		Accurate specific component annotation.
human	ATP5MC3	IPR000454,IPR002379	GO:0015078	proton transmembrane transporter activity	ACCEPT	no		Core molecular function.
human	ATP5MC3	IPR000454	GO:0015986	proton motive force-driven ATP synthesis	ACCEPT	no		Primary biological process function.
human	ATP5MC3	IPR002379	GO:0033177	proton-transporting two-sector ATPase complex, proton-transporting domain	ACCEPT	no		Accurate specific component annotation.
human	ATP6AP2	IPR012493	GO:0016020	membrane	MODIFY	yes	GO:0005765 lysosomal membrane; GO:0010008 endosome membrane; GO:0005789 endoplasmic reticulum membrane; GO:0016471 vacuolar proton-transporting V-type ATPase complex	Replace broad membrane with the specific endomembrane/V-ATPase contexts supported by the UniProt record and literature.
human	ATP6AP2	IPR012493	GO:0038023	signaling receptor activity	KEEP_AS_NON_CORE	yes		Keep as a real but non-core receptor/signaling activity; the stronger PN-relevant molecular function is ATPase regulator/accessory activity.
human	ATP6V0A1	IPR026028	GO:0000220	vacuolar proton-transporting V-type ATPase, V0 domain	ACCEPT	no		The V0-domain annotation is central to ATP6V0A1 identity and is supported by UniProt and human V-ATPase structural work.
human	ATP6V0A1	IPR002490	GO:0033179	proton-transporting V-type ATPase, V0 domain	ACCEPT	no		ATP6V0A1 is the a-subunit of the V0 proton-translocation sector of V-ATPase.
human	ATP6V0A1	IPR002490,IPR026028	GO:0046961	proton-transporting ATPase activity, rotational mechanism	MODIFY	yes	GO:0046961 proton-transporting ATPase activity, rotational mechanism	The GO term itself is correct for the V-ATPase complex activity, but the IEA qualifier should be changed from enables to contributes_to because ATP6V0A1 is a V0-sector subunit rather than an isolated catalytic ATPase.
human	ATP6V0A1	IPR002490	GO:1902600	proton transmembrane transport	ACCEPT	no		ATP6V0A1 is part of the membrane proton-translocation domain, and pathogenic variants perturb proton translocation/acidification.
human	ATP6V0A2	IPR026028	GO:0000220	vacuolar proton-transporting V-type ATPase, V0 domain	ACCEPT	no		ATP6V0A2 is a member of the V-ATPase 116 kDa subunit family and is curated as a V0-complex subunit. The broader V0-domain annotation is correct; the PN-derived lysosomal V0-domain annotation is added separately where lysosomal localization is supported.
human	ATP6V0A2	IPR002490,IPR026028	GO:0046961	proton-transporting ATPase activity, rotational mechanism	MODIFY	yes	GO:0046961 proton-transporting ATPase activity, rotational mechanism	The term is biologically appropriate for ATP6V0A2-containing V-ATPase complexes, but the GOA qualifier should be changed from enables to contributes_to. The contributes_to IBA qualifier is the clearest representation of a single V0 subunit's contribution to the assembled proton pump.
human	ATP6V0A2	IPR002490	GO:1902600	proton transmembrane transport	ACCEPT	no		The V0 sector transfers protons across organelle membranes as part of the V-ATPase. ATP6V0A2 is a V0 a-subunit in this machinery, so the process annotation is appropriate.
human	ATP6V0A4	IPR026028	GO:0000220	vacuolar proton-transporting V-type ATPase, V0 domain	ACCEPT	no		The a subunit is part of the membrane V0 proton-translocation sector, so V0-domain membership is a core cellular-component annotation.
human	ATP6V0A4	IPR002490	GO:0033179	proton-transporting V-type ATPase, V0 domain	ACCEPT	no		The a subunit is part of the membrane V0 proton-translocation sector, so V0-domain membership is a core cellular-component annotation.
human	ATP6V0A4	IPR002490,IPR026028	GO:0046961	proton-transporting ATPase activity, rotational mechanism	ACCEPT	no		Retain the term because ATP6V0A4 contributes to V-ATPase rotational proton-pump activity as a V0-sector subunit. The evidence should be interpreted in the complex-subunit context also captured by the IBA contributes_to row.
human	ATP6V0A4	IPR002490	GO:1902600	proton transmembrane transport	ACCEPT	no		The a4 V0-sector subunit is required for normal V-ATPase proton translocation and renal urinary acidification; retain as a core process-level annotation.
human	ATP6V0B	IPR002379	GO:0033177	proton-transporting two-sector ATPase complex, proton-transporting domain	ACCEPT	no		ATP6V0B is experimentally identified as a five-transmembrane human V-ATPase proteolipid with conserved Glu98 required for H+ transport, and human V-ATPase structures place V0 subunits in the membrane-embedded proton-transfer module. The component annotation is therefore part of the core molecular role of ATP6V0B.
human	ATP6V0B	IPR000245	GO:0033179	proton-transporting V-type ATPase, V0 domain	ACCEPT	no		ATP6V0B is experimentally identified as a five-transmembrane human V-ATPase proteolipid with conserved Glu98 required for H+ transport, and human V-ATPase structures place V0 subunits in the membrane-embedded proton-transfer module. The component annotation is therefore part of the core molecular role of ATP6V0B.
human	ATP6V0B	IPR000245	GO:0046961	proton-transporting ATPase activity, rotational mechanism	ACCEPT	no		ATP6V0B is not the ATP-hydrolytic catalytic subunit, but it is an essential V0 c-ring proteolipid required for proton translocation by the rotary V-ATPase. This is the correct complex-level molecular function for the ATP6V0B-containing V-ATPase machinery.
human	ATP6V0C	IPR002379	GO:0033177	proton-transporting two-sector ATPase complex, proton-transporting domain	ACCEPT	no		Core complex membership annotation. The V-ATPase is a two-sector enzyme with V1 (catalytic) and V0 (proton-transporting) domains. ATP6V0C is a structural component of the V0 domain.
human	ATP6V0C	IPR000245,IPR011555	GO:0033179	proton-transporting V-type ATPase, V0 domain	ACCEPT	no		Core complex membership annotation. Nine copies of ATP6V0C form the majority of the c-ring in the V0 domain. This is the most specific and accurate complex annotation for this protein.
human	ATP6V0C	IPR000245,IPR011555	GO:0046961	proton-transporting ATPase activity, rotational mechanism	ACCEPT	no		Core molecular function annotation. The V-ATPase uses a rotary mechanism where ATP hydrolysis drives rotation of the c-ring, enabling proton translocation. This is well-established biochemically and structurally.
human	ATP6V0D1	IPR016727	GO:1902600	proton transmembrane transport	ACCEPT	no		ATP6V0D1 functions in the V-ATPase complex that translocates protons and acidifies intracellular compartments. This is the principal biological process supported for the d1 subunit.
human	ATP6V0D2	IPR016727	GO:0033179	proton-transporting V-type ATPase, V0 domain	ACCEPT	no		This is the most precise cellular component annotation for ATP6V0D2 - it is specifically a subunit of the V0 domain. This annotation correctly distinguishes it from V1 domain subunits.
human	ATP6V0D2	IPR002843,IPR016727	GO:0046961	proton-transporting ATPase activity, rotational mechanism	ACCEPT	no		Correct annotation from InterPro mapping. The d2 subunit is integral to the rotational mechanism of the V-ATPase, but the biologically appropriate qualifier for this structural subunit is contributes_to.
human	ATP6V0E1	IPR008389,IPR017385	GO:0033179	proton-transporting V-type ATPase, V0 domain	ACCEPT	no		V0 domain membership is directly confirmed by cryo-EM structures (PMID:33065002).
human	ATP6V0E1	IPR008389,IPR017385	GO:0046961	proton-transporting ATPase activity, rotational mechanism	ACCEPT	no		The V-ATPase employs a rotational mechanism. Subunit e1 as a V0 structural component contributes to this activity. The annotation is appropriate with contributes_to semantics implied.
human	ATP6V0E1	IPR008389,IPR017385	GO:1902600	proton transmembrane transport	ACCEPT	no		Proton transmembrane transport is the core function. Multiple lines of evidence support this annotation.
human	ATP6V0E2	IPR008389,IPR017385	GO:0033179	proton-transporting V-type ATPase, V0 domain	ACCEPT	no		Correct complex/domain membership supported by InterPro family signatures (IPR008389, IPR017385) and by the UniProt SUBUNIT description.
human	ATP6V0E2	IPR008389,IPR017385	GO:0046961	proton-transporting ATPase activity, rotational mechanism	ACCEPT	no		The molecular function is correct for the V-ATPase family. The enables qualifier is the GOA convention for complex subunits via InterPro; the IBA annotation already captures the more precise contributes_to.
human	ATP6V0E2	IPR008389,IPR017385	GO:1902600	proton transmembrane transport	ACCEPT	no		Core process of the V-ATPase, correctly inferred from InterPro family membership and corroborated by experimental evidence.
human	ATP6V1A	IPR000194,IPR020003	GO:0005524	ATP binding	ACCEPT	no		ATP binding is directly demonstrated at the A-B subunit interface by crystallography and cryo-EM. This is a core molecular function annotation.
human	ATP6V1A	IPR005725	GO:0016887	ATP hydrolysis activity	ACCEPT	no		ATP hydrolysis at the A-B interface is the primary molecular activity of the V1 domain, and the A subunit bears the catalytic residues.
human	ATP6V1A	IPR004100,IPR022878,IPR036121	GO:0046034	ATP metabolic process	MARK_AS_OVER_ANNOTATED	yes		While technically correct (ATP is hydrolyzed), the primary annotation should focus on the proton transport function. ATP hydrolysis by V-ATPase is energetically coupled to proton transport, not an end in itself. The more specific proton transport terms are more informative.
human	ATP6V1A	IPR004100,IPR005725,IPR036121	GO:1902600	proton transmembrane transport	ACCEPT	no		Proton transmembrane transport is the primary biological process for V-ATPase.
human	ATP6V1B1	IPR000194,IPR020003	GO:0005524	ATP binding	ACCEPT	no		ATP binding at the non-catalytic site is a conserved property of V-ATPase B subunits and is consistent with the InterPro nucleotide-binding domain assignment and the UniProt ATP-binding feature.
human	ATP6V1B1	IPR005723	GO:0033180	proton-transporting V-type ATPase, V1 domain	ACCEPT	no		Correct V1 domain membership; the more specific vacuolar V1 domain term (GO:0000221) is also annotated with direct structural support.
human	ATP6V1B1	IPR004100	GO:0046034	ATP metabolic process	MARK_AS_OVER_ANNOTATED	yes		Overly broad and derived from the catalytic A-subunit-like domain signature. ATP hydrolysis is performed by the catalytic A subunits; B1 binds but does not hydrolyze ATP. Proton transmembrane transport better captures the relevant process.
human	ATP6V1B1	IPR005723	GO:0046961	proton-transporting ATPase activity, rotational mechanism	KEEP_AS_NON_CORE	yes		The rotational ATPase activity is a property of the holoenzyme; B1 is an essential non-catalytic subunit. Accepting the term as a subunit contribution is reasonable but it is not an autonomous B1 function, so it is retained as non-core.
human	ATP6V1B2	IPR000194,IPR020003	GO:0005524	ATP binding	ACCEPT	no		The B subunit participates in ATP binding at the non-catalytic AB interface. IEA from InterPro is appropriate.
human	ATP6V1B2	IPR005723	GO:0033180	proton-transporting V-type ATPase, V1 domain	ACCEPT	no		Core structural annotation for the B subunit of V-ATPase V1 domain.
human	ATP6V1B2	IPR004100	GO:0046034	ATP metabolic process	MARK_AS_OVER_ANNOTATED	yes		Too broad; the specific proton transport and acidification terms are more informative for V-ATPase function.
human	ATP6V1B2	IPR005723	GO:0046961	proton-transporting ATPase activity, rotational mechanism	ACCEPT	no		Core molecular function of V-ATPase. The B subunit enables this function as part of the complex even though it lacks the catalytic residues itself.
human	ATP6V1C1	IPR004907,IPR036132	GO:1902600	proton transmembrane transport	ACCEPT	no		Core biological process of V-ATPase; the C1 subunit is required for V1 assembly and thus for proton transport.
human	ATP6V1C2	IPR036132	GO:0015078	proton transmembrane transporter activity	MARK_AS_OVER_ANNOTATED	yes		Broad InterPro IEA transfer; subunit C is a regulatory/structural V1 subunit and is not itself the proton transporter. The more specific rotational-mechanism term (GO:0046961) is preferred for representing the complex's function.
human	ATP6V1C2	IPR004907,IPR036132	GO:0033180	proton-transporting V-type ATPase, V1 domain	ACCEPT	no		Definitionally correct; subunit C2 is a component of the V1 domain as established for the C-subunit family.
human	ATP6V1C2	IPR004907,IPR036132	GO:1902600	proton transmembrane transport	ACCEPT	no		Core biological process of the V-ATPase; subunit C is required for assembly of the catalytic V1 sector and therefore for proton transport by the holoenzyme.
human	ATP6V1D	IPR002699	GO:0046961	proton-transporting ATPase activity, rotational mechanism	ACCEPT	no		The proton-transporting ATPase activity via rotational mechanism is the core molecular function of the complex in which ATP6V1D is an indispensable structural component. The IBA annotation with contributes_to is more precise, but this IEA is consistent.
human	ATP6V1E1	IPR002842	GO:0033178	proton-transporting two-sector ATPase complex, catalytic domain	ACCEPT	no		The V1 sector is the catalytic (ATP-hydrolyzing) domain of the two-sector V-ATPase. Subunit E is part of this domain.
human	ATP6V1E1	IPR002842	GO:0046961	proton-transporting ATPase activity, rotational mechanism	ACCEPT	no		Consistent with established V-ATPase biology.
human	ATP6V1E1	IPR002842	GO:1902600	proton transmembrane transport	ACCEPT	no		Consistent with IBA and TAS annotations.
human	ATP6V1E2	IPR002842	GO:0033178	proton-transporting two-sector ATPase complex, catalytic domain	ACCEPT	no		Subunit E is part of the V1 (catalytic) sector of the V-ATPase, so this complex-membership annotation correctly captures the cellular-component context and is consistent with the curated complex membership documented in UniProt.
human	ATP6V1E2	IPR002842	GO:1902600	proton transmembrane transport	MARK_AS_OVER_ANNOTATED	yes		This IEA annotation is redundant with the IBA annotation to the identical term (GO:1902600). The IBA version is retained as the representative core annotation; the duplicate IEA adds no information.
human	ATP6V1F	IPR005772	GO:0033180	proton-transporting V-type ATPase, V1 domain	ACCEPT	no		Subunit F is a defining structural component of the V1 domain central rotor, confirmed by cryo-EM (PMID:33065002) and biochemical data (PMID:18752060).
human	ATP6V1F	IPR008218,IPR036906	GO:0034220	monoatomic ion transmembrane transport	MARK_AS_OVER_ANNOTATED	yes		The generic monoatomic ion transmembrane transport is subsumed by the more specific proton transmembrane transport annotations. Redundant and less informative.
human	ATP6V1F	IPR005772,IPR008218	GO:0046961	proton-transporting ATPase activity, rotational mechanism	ACCEPT	no		Core molecular function of the V-ATPase; subunit F is an essential structural component of the rotary mechanism.
human	ATP6V1F	IPR005772	GO:1902600	proton transmembrane transport	ACCEPT	no		Core biological process of V-ATPase.
human	ATP6V1G1	IPR005124	GO:1902600	proton transmembrane transport	ACCEPT	no		Proton transmembrane transport is the core biological process driven by the V-ATPase. As a structural component of the complex, G1 is rightly annotated as involved in this process.
human	ATP6V1G2	IPR005124	GO:1902600	proton transmembrane transport	ACCEPT	no		This is the core biological process of the V-ATPase and is directly supported by the UniProt FUNCTION description. The InterPro-based IEA is consistent with the well-established mechanism.
human	ATP6V1G3	IPR005124	GO:0016471	vacuolar proton-transporting V-type ATPase complex	ACCEPT	no		Core, well-supported cellular-component annotation; the G subunit is an integral part of the assembled V-ATPase complex.
human	ATP6V1G3	IPR005124	GO:1902600	proton transmembrane transport	ACCEPT	no		Core biological-process annotation directly consistent with V-ATPase function and with the renal proton-secretion role of the G3-containing pump.
human	ATP6V1H	IPR004908,IPR011987	GO:0000221	vacuolar proton-transporting V-type ATPase, V1 domain	ACCEPT	no		V1 domain membership is supported by structural and functional data.
human	ATP6V1H	IPR004908	GO:0046961	proton-transporting ATPase activity, rotational mechanism	ACCEPT	no		The V-ATPase uses a rotational mechanism for proton translocation. Subunit H contributes to this complex activity as a regulatory component.
human	ATP6V1H	IPR004908,IPR011987	GO:1902600	proton transmembrane transport	ACCEPT	no		Proton transmembrane transport is the fundamental function of the V-ATPase complex. Subunit H is essential for this activity as a regulatory component.
human	ATP7B	IPR001757	GO:0005524	ATP binding	KEEP_AS_NON_CORE	yes		Redundant with IDA from PMID:16567646.
human	ATP7B	IPR023299	GO:0000166	nucleotide binding	MARK_AS_OVER_ANNOTATED	yes		Redundant with the more specific GO:0005524 (ATP binding) which has IDA support.
human	ATP7B	IPR001757	GO:0016887	ATP hydrolysis activity	KEEP_AS_NON_CORE	yes		While correct, the ATPase activity is part of the copper transport mechanism already captured by GO:0140581. Acceptable as supplementary.
human	ATP7B	IPR006121,IPR017969,IPR036163	GO:0046872	metal ion binding	MARK_AS_OVER_ANNOTATED	yes		Too general. The specific copper ion binding term (GO:0005507) with IDA evidence is preferred.
human	ATP7B	IPR027256	GO:0006812	monoatomic cation transport	MARK_AS_OVER_ANNOTATED	yes		Too general. The specific copper ion transport term (GO:0006825) with IDA evidence is preferred.
human	AUP1	IPR048056	GO:0036503	ERAD pathway	ACCEPT	no		AUP1 associates with the HRD1-SEL1L complex and recruits UBE2G2; depletion impairs degradation of misfolded ER proteins.
human	AUP1	IPR003892	GO:0043130	ubiquitin binding	ACCEPT	no		The CUE domain is directly demonstrated as a ubiquitin-binding domain required for ubiquitination and LD clustering.
human	AXIN1	IPR043581	GO:0090090	negative regulation of canonical Wnt signaling pathway	ACCEPT	no		Core function of AXIN1, supported by domain analysis and experimental evidence.
human	AZIN2	IPR000183,IPR009006,IPR022644	GO:0003824	catalytic activity	REMOVE	yes		Electronic over-propagation onto a catalytically dead paralog. Remove.
human	AZIN2	IPR002433	GO:0006596	polyamine biosynthetic process	KEEP_AS_NON_CORE	yes		Valid but non-core / secondary.
human	BACH2	IPR004826,IPR004827,IPR008917,IPR046347	GO:0006355	regulation of DNA-templated transcription	ACCEPT	no		Correct but more general than GO:0006357 already captured by IBA. As an IEA derived from domain associations, this broad annotation is acceptable and will be naturally superseded by the more specific annotations.
human	BAG1	IPR003103,IPR036533,IPR039773	GO:0051087	protein-folding chaperone binding	ACCEPT	no		Correct annotation based on domain architecture. BAG domain mediates Hsp70/Hsc70 binding, which is the core molecular function.
human	BAG2	IPR037689	GO:0000774	adenyl-nucleotide exchange factor activity	ACCEPT	no		The BAG domain confers nucleotide-exchange activity on HSP70/HSC70; this IEA annotation agrees with direct biochemical evidence.
human	BAG2	IPR003103,IPR037689	GO:0051087	protein-folding chaperone binding	ACCEPT	no		Direct binding of BAG2 to the HSP/HSC70 ATPase domain is well established and is the basis of its NEF activity.
human	BAG3	IPR003103,IPR036533,IPR039773	GO:0051087	protein-folding chaperone binding	ACCEPT	no		The BAG domain and IPV motifs bind HSP70/HSC70 and small heat shock proteins, respectively.
human	BAIAP2	IPR013606	GO:0007009	plasma membrane organization	ACCEPT	no		Core function. Deep research shows IRSp53 plays a central role in membrane shape homeostasis at the nanoscale, detecting curvature and coordinating membrane remodeling.
human	BAIAP2	IPR030128	GO:0008093	cytoskeletal anchor activity	ACCEPT	no		The I-BAR domain binds membranes while the SH3 domain recruits actin effectors, creating a molecular bridge. Supported by TAS evidence from PMID:10343108.
human	BAIAP2	IPR030128	GO:0032956	regulation of actin cytoskeleton organization	ACCEPT	no		Supported by IMP evidence (PMID:19366662). IRSp53 is necessary for CDC42-mediated and RAC1-mediated reorganization of actin cytoskeleton.
human	BAIAP2L1	IPR013606	GO:0007009	plasma membrane organization	ACCEPT	no		This is a core function of IRTKS. The I-BAR domain directly participates in membrane organization by sensing curvature and recruiting actin machinery to restore membrane topology.
human	BAIAP2L1	IPR030060	GO:0030833	regulation of actin filament polymerization	MODIFY	yes	GO:0030838 positive regulation of actin filament polymerization	More specific term exists. IRTKS positively regulates actin polymerization rather than general regulation.
human	BAIAP2L2	IPR013606	GO:0007009	plasma membrane organization	ACCEPT	no		BAIAP2L2/Pinkbar is directly involved in organizing plasma membrane structure through its unique I-BAR domain that generates planar membrane sheets rather than tubules [PMID:21743456]. This is a core function of the protein.
human	BBIP1	IPR028233	GO:0034464	BBSome	ACCEPT	no		Family-level electronic inference correctly assigns BBSome membership, consistent with direct evidence.
human	BBIP1	IPR028233	GO:0060271	cilium assembly	ACCEPT	no		Cilium assembly is a core, experimentally supported process for BBIP1; the IEA is corroborated.
human	BBS10	IPR002423	GO:0005524	ATP binding	ACCEPT	no		Domain-based ATP-binding annotation is consistent with the conserved group II chaperonin fold (UniProt 'Belongs to the TCP-1 chaperonin family'; FUNCTION 'assists the folding of proteins upon ATP hydrolysis'). Retained as a molecular function, with the caveat that catalytic activity is unproven.
human	BBS10	IPR042619	GO:0051131	chaperone-mediated protein complex assembly	ACCEPT	no		Redundant with the IBA and IMP annotations to GO:0051131 but correct and well supported; represents the core function of BBS10.
human	BBS12	IPR002423	GO:0005524	ATP binding	MARK_AS_OVER_ANNOTATED	yes		Inferred only from the broad chaperonin family signature; no direct evidence that this divergent BBS subfamily member binds or hydrolyzes ATP.
human	BBS12	IPR042984	GO:0051131	chaperone-mediated protein complex assembly	ACCEPT	no		Concordant with direct experimental evidence (PMID:20080638) and with the BBS12-specific InterPro signature; represents the core function.
human	BBS2	IPR016616	GO:1905515	non-motile cilium assembly	ACCEPT	no		BBSome is required for primary (non-motile/sensory) cilium biogenesis and cargo sorting; this is the most precise process term.
human	BBS7	IPR016575	GO:0034464	BBSome	ACCEPT	no		BBSome membership is correct and corroborated by experimental IDA annotations.
human	BBS7	IPR016575	GO:1905515	non-motile cilium assembly	ACCEPT	no		BBS7 and the BBSome act in assembly and function of primary non-motile cilia (sensory cilia, retina); the InterPro-based involvement is consistent with established biology.
human	BCAP31	IPR008417	GO:0005783	endoplasmic reticulum	ACCEPT	no		Correct general localization. The more specific ER membrane term is also present.
human	BCAP31	IPR008417	GO:0006886	intracellular protein transport	ACCEPT	no		Correct general process. BCAP31 is a protein translocation chaperone for membrane proteins.
human	BCAP31	IPR008417	GO:0016020	membrane	ACCEPT	no		Technically correct though very general. More specific ER membrane annotation is also present.
human	BCL2	IPR003093,IPR004725,IPR020717,IPR020726,IPR020728,IPR020731,IPR026298,IPR036834	GO:0042981	regulation of apoptotic process	MODIFY	yes	GO:0043066 negative regulation of apoptotic process	BCL2 specifically negatively regulates apoptosis. The more specific term GO:0043066 (negative regulation of apoptotic process) would be more appropriate and informative.
human	BCL2L1	IPR003093,IPR004725,IPR013279,IPR020717,IPR020726,IPR020728,IPR020731,IPR026298,IPR036834	GO:0042981	regulation of apoptotic process	ACCEPT	no		"Accurate annotation capturing the core regulatory function. While ""negative regulation"" would be more precise for Bcl-xL, this general regulatory term is still appropriate given that the BCL2L1 locus produces both anti-apoptotic (Bcl-xL) and pro-apoptotic (Bcl-xS) isoforms."
human	BCL2L12	IPR036834	GO:0042981	regulation of apoptotic process	ACCEPT	no		The IEA annotation from InterPro domain mapping is appropriate as BCL2L12 does regulate apoptosis through its Bcl-2 family membership. More specific annotations (GO:0043066 negative regulation) are present to provide detailed function. This broader term acceptable as general context.
human	BCL2L13	IPR042398	GO:0006915	apoptotic process	KEEP_AS_NON_CORE	yes		A pro-apoptotic capacity is genuine but context/overexpression-dependent and secondary to the conserved mitophagy-receptor function.
human	BCL2L13	IPR036834	GO:0042981	regulation of apoptotic process	KEEP_AS_NON_CORE	yes		Supported by the apoptosis literature but context-dependent and secondary to the mitophagy-receptor function.
human	BICC1	IPR004087	GO:0003676	nucleic acid binding	MODIFY	yes	GO:0003723 RNA binding	While technically not wrong (RNA is a nucleic acid), this term is overly broad and does not capture the specific RNA-binding function of BICC1. The more specific term GO:0003723 (RNA binding) should be used.
human	BIRC6	IPR022103	GO:0032465	regulation of cytokinesis	ACCEPT	no		Regulation of cytokinesis is a core function of BIRC6, well-established by the detailed mechanistic study in PMID:18329369.
human	BNIP3L	IPR010548	GO:0005740	mitochondrial envelope	MODIFY	yes	GO:0005741 mitochondrial outer membrane	The more precise and well-supported localization is the mitochondrial outer membrane; replace the broader envelope term.
human	BRAF	IPR000719,IPR017441	GO:0005524	ATP binding	ACCEPT	no		IEA mechanical propagation supports a canonical BRAF function or localization directly demonstrated experimentally in this file (PMID:18567582 IDA, PMID:19710016 EXP, PMID:21441910 EXP, PMID:29433126 IDA/IMP) and/or already ACCEPTed via the IBA propagation batch (PR #448) or the Reactome TAS rows (PR #440). Mechanically consolidated to ACCEPT with a uniform template across the 8 canonical IEA rows (protein kinase activity, S/T kinase, ATP binding, cytoplasm, PM, signal transduction, neg-reg apoptosis, S kinase); the GO:0005634 nucleus IEA row is held back for separate per-row consideration (BRAF nuclear localization is reported but tissue/context-specific), and the 6 SynGO/tissue-specific IEA rows (postsynapse, neuron projection, cell body, glutamatergic synapse, postsynaptic modulation of chemical synaptic transmission, mitochondrion) are held back for a uniform KEEP_AS_NON_CORE batch.
human	BRAF	IPR003116	GO:0007165	signal transduction	ACCEPT	no		IEA mechanical propagation supports a canonical BRAF function or localization directly demonstrated experimentally in this file (PMID:18567582 IDA, PMID:19710016 EXP, PMID:21441910 EXP, PMID:29433126 IDA/IMP) and/or already ACCEPTed via the IBA propagation batch (PR #448) or the Reactome TAS rows (PR #440). Mechanically consolidated to ACCEPT with a uniform template across the 8 canonical IEA rows (protein kinase activity, S/T kinase, ATP binding, cytoplasm, PM, signal transduction, neg-reg apoptosis, S kinase); the GO:0005634 nucleus IEA row is held back for separate per-row consideration (BRAF nuclear localization is reported but tissue/context-specific), and the 6 SynGO/tissue-specific IEA rows (postsynapse, neuron projection, cell body, glutamatergic synapse, postsynaptic modulation of chemical synaptic transmission, mitochondrion) are held back for a uniform KEEP_AS_NON_CORE batch.
human	BRCA1	IPR011364	GO:0004842	ubiquitin-protein transferase activity	ACCEPT	no		This IEA annotation correctly identifies BRCA1s E3 ubiquitin ligase activity based on its RING domain. While redundant with the IBA annotation, it provides complementary evidence from protein domain analysis. The RING domain at the N-terminus is essential for BRCA1s E3 ligase function in complex with BARD1.
human	CACNB2	IPR000584,IPR005444	GO:0005245	voltage-gated calcium channel activity	MODIFY	yes	GO:0005891 voltage-gated calcium channel complex	CaVbeta2 is an auxiliary subunit, not the pore-forming subunit. It does not have intrinsic channel activity. The annotation should reflect its role as a regulator/auxiliary rather than having the activity itself. However, there is an IDA annotation to the same term from PMID:1309651 which is more nuanced.
human	CACUL1	IPR001373	GO:0006511	ubiquitin-dependent protein catabolic process	MARK_AS_OVER_ANNOTATED	yes		Pure domain-transfer from the cullin fold with no direct evidence; CACUL1 is not demonstrated to function as a CRL scaffold or in proteasomal degradation.
human	CACUL1	IPR001373	GO:0031625	ubiquitin protein ligase binding	MARK_AS_OVER_ANNOTATED	yes		Pure domain-transfer with no direct evidence that CACUL1 binds a ubiquitin ligase or acts within a CRL.
human	CACYBP	IPR037893	GO:0015631	tubulin binding	MARK_AS_OVER_ANNOTATED	yes		No direct experimental evidence in the cached literature supports tubulin binding as a core CACYBP function; it is an automated domain-based transfer.
human	CACYBP	IPR037893	GO:0044548	S100 protein binding	ACCEPT	no		CACYBP interacts with multiple S100 proteins in a calcium-dependent manner.
human	CALR	IPR001580,IPR009169	GO:0006457	protein folding	ACCEPT	no		Consistent with experimental and phylogenetic evidence for chaperone-assisted folding.
human	CALR3	IPR001580,IPR009169	GO:0005783	endoplasmic reticulum	KEEP_AS_NON_CORE	yes		The annotation is accurate but generic; the more precise ER lumen term (GO:0005788) better captures the localization, so this broad term is retained as non-core.
human	CALR3	IPR001580,IPR009169	GO:0006457	protein folding	ACCEPT	no		The InterPro2GO transfer is consistent with the documented chaperone role of CALR3 in folding sperm client proteins such as ADAM3.
human	CAMK2A	IPR000719,IPR008271	GO:0004672	protein kinase activity	ACCEPT	no		While broad, this annotation is correct and represents the parent term of the more specific calcium/calmodulin-dependent protein kinase activity. IEA annotations from InterPro domains are appropriate for capturing general molecular functions based on conserved domains.
human	CAND1	IPR039852	GO:0010265	SCF complex assembly	ACCEPT	no		Strongly supported core function consistent with InterPro/experimental evidence.
human	CAND2	IPR039852	GO:0010265	SCF complex assembly	ACCEPT	no		Core biological process; redundant with the IBA assignment and consistent with the CAND family's exchange-factor role.
human	CANX	IPR001580,IPR009033,IPR018124	GO:0005509	calcium ion binding	ACCEPT	no		Same well-supported core molecular function as the IBA/TAS calcium annotations.
human	CANX	IPR001580	GO:0006457	protein folding	ACCEPT	no		Consistent with experimental and phylogenetic evidence for chaperone-assisted glycoprotein folding.
human	CAPG	IPR007122	GO:0051015	actin filament binding	ACCEPT	no		Actin filament binding is a core function of CAPG. This InterPro-based annotation is redundant with the IBA annotation but is correct.
human	CASP12	IPR001309,IPR002138,IPR002398,IPR011600	GO:0006508	proteolysis	REMOVE	yes		Process annotation dependent on catalytic activity the protein lacks. Remove.
human	CASP12	IPR015917	GO:0008234	cysteine-type peptidase activity	REMOVE	yes		Electronic over-propagation of peptidase activity onto an inactive family member. Remove.
human	CASP12	IPR001315	GO:0042981	regulation of apoptotic process	KEEP_AS_NON_CORE	yes		Valid but non-core / secondary.
human	CASP14	IPR001309,IPR002138,IPR002398,IPR011600	GO:0004197	cysteine-type endopeptidase activity	ACCEPT	no		"CASP14 is indeed a cysteine-type endopeptidase (EC 3.4.22.-) with a catalytic cysteine-histidine dyad [UniProt P31944; PMID:10203698 ""cysteine-aspartic acid protease""]. This annotation accurately represents the core catalytic activity and is supported by TAS evidence (PMID:10203698)."
human	CASP9	IPR001315	GO:0042981	regulation of apoptotic process	ACCEPT	no		This general regulatory term is appropriate as CASP9 is involved in apoptosis regulation through both pro-apoptotic (isoform 1) and anti-apoptotic (isoform 2) mechanisms. The InterPro association correctly identifies this function.
human	CBS	IPR001216	GO:0006535	L-cysteine biosynthetic process from L-serine	ACCEPT	no		CBS function in the transsulfuration pathway leads to cysteine biosynthesis.
human	CBS	IPR005857	GO:0019343	L-cysteine biosynthetic process via L-cystathionine	ACCEPT	no		This is more specific than GO:0006535 and correctly captures that cysteine is produced via the cystathionine intermediate generated by CBS.
human	CCDC47	IPR012879	GO:0032469	endoplasmic reticulum calcium ion homeostasis	KEEP_AS_NON_CORE	yes		Loss-of-function patient cells show decreased ER Ca2+ storage and impaired Ca2+ signaling, supporting a role in ER calcium homeostasis; retain as a non-core contextual function.
human	CCL11	IPR000827,IPR001811,IPR036048	GO:0006955	immune response	ACCEPT	no		Immune response is a broad parent term. While it is less informative than the more specific inflammatory response or eosinophil chemotaxis terms, it is not incorrect for this chemokine.
human	CD247	IPR003110	GO:0004888	transmembrane signaling receptor activity	ACCEPT	no		Correct. CD3ζ is a transmembrane protein that transduces signals as part of TCR complex.
human	CD247	IPR003110	GO:0007166	cell surface receptor signaling pathway	ACCEPT	no		Correct general term. CD3ζ functions in TCR signaling at cell surface.
human	CD247	IPR003110	GO:0016020	membrane	ACCEPT	no		Correct but very general. More specific term (plasma membrane) is preferred.
human	CD28	IPR008093	GO:0006955	immune response	ACCEPT	no		While broad, the IEA annotation from InterPro mapping is correct. CD28 is a central player in adaptive immune responses. More specific terms (T cell costimulation, T cell activation) provide the needed detail.
human	CD28	IPR008093	GO:0016020	membrane	ACCEPT	no		Correct but very broad. More specific CC annotations are available. Acceptable as a broad IEA mapping from InterPro.
human	CD28	IPR040216	GO:0042129	regulation of T cell proliferation	ACCEPT	no		Correct IEA annotation. The more specific child term GO:0042102 (positive regulation of T cell proliferation) is also annotated with experimental evidence. This broader IEA term is acceptable.
human	CD47	IPR006704	GO:0022409	positive regulation of cell-cell adhesion	ACCEPT	no		Cell-cell adhesion is a validated function of CD47.
human	CD47	IPR006704	GO:0050729	positive regulation of inflammatory response	KEEP_AS_NON_CORE	yes		This is a pleiotropic effect, not the core function.
human	CD47	IPR006704	GO:0050766	positive regulation of phagocytosis	MODIFY	yes	GO:0050765 negative regulation of phagocytosis	CD47's core function is inhibiting phagocytosis via the SIRPalpha checkpoint. This annotation is fundamentally wrong.
human	CD47	IPR006704	GO:0070053	thrombospondin receptor activity	ACCEPT	no		Thrombospondin receptor activity is a core function.
human	CDC25B	IPR000751	GO:1902751	positive regulation of cell cycle G2/M phase transition	ACCEPT	no		This IEA annotation from InterPro mapping is correct and consistent with the IBA and IDA annotations for GO:0010971 (positive regulation of G2/M transition of mitotic cell cycle). This is the core function of CDC25B.
human	CDH1	IPR000233,IPR002126,IPR015919	GO:0005509	calcium ion binding	ACCEPT	no		Core CDH1 molecular function — Ca2+ binding via the EC-domain linkers is an obligate step in homophilic cadherin adhesion. IEA batch (batch 3 of #348).
human	CDH1	IPR020894	GO:0007155	cell adhesion	ACCEPT	no		Core CDH1 biological process — cell adhesion is the defining function of E-cadherin. IEA batch (batch 3 of #348).
human	CDH1	IPR000233,IPR002126	GO:0007156	homophilic cell-cell adhesion	ACCEPT	no		Core CDH1 biological process — homophilic cell-cell adhesion via the ectodomain strand-swap mechanism is the defining activity of E-cadherin. IEA batch (batch 3 of #348).
human	CDH1	IPR002126,IPR015919	GO:0016020	membrane	MARK_AS_OVER_ANNOTATED	yes		GO:0016020 membrane is an uninformative broad parent term — CDH1 is a single-pass transmembrane protein but the informative CC terms are GO:0005886 plasma membrane and GO:0005912 adherens junction (both ACCEPTed elsewhere); the generic membrane term adds no annotation value. Consistent with the MARK_AS_OVER_ANNOTATED treatment of the equally generic GO:0005737 cytoplasm rows. Action reconciled with the IDA GO:0016020 row in this file (#348).
human	CDH1	IPR039808	GO:0098609	cell-cell adhesion	ACCEPT	no		Core CDH1 biological process — cell-cell adhesion is the defining function of E-cadherin; consistent with GO:0044331 (IBA ACCEPT) and GO:0007155 (IEA ACCEPT). IEA batch (batch 3 of #348).
human	CDH23	IPR002126,IPR015919	GO:0005509	calcium ion binding	ACCEPT	no		Cadherin repeats use calcium to rigidify extracellular-domain interfaces and support adhesion.
human	CDH23	IPR020894	GO:0007155	cell adhesion	ACCEPT	no		CDH23 is a cadherin family adhesion protein required for stereocilia bundle organization; the broad adhesion terms are appropriate, though stereocilium/tip-link context is the most informative framing.
human	CDH23	IPR002126	GO:0007156	homophilic cell-cell adhesion	MARK_AS_OVER_ANNOTATED	yes		The InterPro2GO mapping propagated a generic cadherin-family homophilic adhesion term, but CDH23 specifically forms an antiparallel heterodimer with PCDH15 via cadherin repeats 1-2, defining the upper part of the stereocilia tip link. The broader cell adhesion term (GO:0007155) and stereocilium-specific terms are retained as accurate; homophilic adhesion is not supported for this gene.
human	CDH23	IPR002126,IPR015919	GO:0016020	membrane	ACCEPT	no		The broad membrane annotation is true, with stereocilium/hair-bundle membrane localization being more informative.
human	CDK1	IPR000719,IPR008271	GO:0004672	protein kinase activity	ACCEPT	no		True but generic. The more specific cyclin-dependent protein kinase activity terms are more informative.
human	CDK2	IPR000719,IPR017441	GO:0005524	ATP binding	ACCEPT	no		Required for kinase catalysis; CDK2 crystal structures resolve bound ATP.
human	CDK5	IPR000719,IPR017441	GO:0005524	ATP binding	ACCEPT	no		CDK5 is a CDK-family proline-directed serine/threonine protein kinase that uses ATP and is activated in CDK5R-containing kinase complexes; tau/MAPT and other neuronal proteins are established substrates.
human	CDKN1C	IPR003175	GO:0004861	cyclin-dependent protein serine/threonine kinase inhibitor activity	ACCEPT	no		Core molecular function. The N-terminal KID domain binds to and inhibits cyclin E/CDK2, cyclin A/CDK2, and cyclin D/CDK4 complexes.
human	CDKN1C	IPR003175	GO:0051726	regulation of cell cycle	ACCEPT	no		Core function. p57Kip2 regulates cell cycle by inhibiting G1 cyclin/CDK complexes.
human	CFTR	IPR009147,IPR011527,IPR036640	GO:0016020	membrane	ACCEPT	no		CFTR is an integral membrane protein with multiple membrane-spanning domains [PMID:11524016]. While this term is less specific than plasma membrane or apical plasma membrane, it correctly captures CFTR's membrane association.
human	CFTR	IPR011527	GO:0055085	transmembrane transport	ACCEPT	no		CFTR mediates transmembrane transport of anions (chloride and bicarbonate) [PMID:19019741]. While this is a general term, it correctly captures CFTR's fundamental transport function.
human	CFTR	IPR011527	GO:0140359	ABC-type transporter activity	ACCEPT	no		CFTR belongs to the ABC transporter superfamily and has the characteristic ABC domain architecture [PMID:11524016]. While CFTR functions as an ion channel rather than an active transporter, the ABC-type transporter activity term appropriately describes its protein family classification.
human	CHAF1B	IPR045145	GO:0006335	DNA replication-dependent chromatin assembly	KEEP_AS_NON_CORE	yes		Electronic InterPro2GO duplicate of the experimentally supported core process term; correct but redundant.
human	CHAMP1	IPR039330	GO:0051315	attachment of mitotic spindle microtubules to kinetochore	ACCEPT	no		Electronic annotation from InterPro domain (CAMP domain IPR039330). This is the defining function of the CAMP domain family.
human	CHCHD4	IPR039289	GO:0015035	protein-disulfide reductase activity	MODIFY	yes	GO:0015036 disulfide oxidoreductase activity	Same concern as IBA — CHCHD4 is primarily an oxidase, not a reductase.
human	CHCHD4	IPR039289	GO:0045041	protein import into mitochondrial intermembrane space	ACCEPT	no		Correct. Redundant with IBA for same term.
human	CHMP1A	IPR005024	GO:0007034	vacuolar transport	ACCEPT	no		InterPro-based annotation consistent with CHMP1A's role as an ESCRT-III/Snf7 family member involved in endolysosomal trafficking.
human	CHMP1B	IPR005024	GO:0007034	vacuolar transport	REMOVE	yes		"This term is based on InterPro domain annotation but uses yeast-specific vocabulary (""vacuolar""). For human CHMP1B, lysosomal/endosomal transport terms are more appropriate."
human	CHMP2A	IPR005024	GO:0007034	vacuolar transport	ACCEPT	no		Core ESCRT-III function.
human	CHMP2B	IPR005024	GO:0007034	vacuolar transport	ACCEPT	no		The SNF7 domain annotation appropriately maps to vacuolar transport function. In mammalian cells, this corresponds to lysosomal transport pathways.
human	CHMP3	IPR005024	GO:0007034	vacuolar transport	ACCEPT	no		This reflects the conserved function of Vps24 in vacuolar protein sorting. InterPro domain mapping correctly identifies this core function.
human	CHMP4A	IPR005024	GO:0007034	vacuolar transport	MODIFY	yes	GO:0071985 multivesicular body sorting pathway	CHMP4A is best represented by ESCRT-III-mediated MVB sorting and ILV/membrane fission, not generic vacuolar transport.
human	CHMP4B	IPR005024	GO:0007034	vacuolar transport	MODIFY	yes	GO:0071985 multivesicular body sorting pathway	Multivesicular body sorting is the informative ESCRT-III process; vacuolar transport is too broad for human CHMP4B.
human	CHMP4C	IPR005024	GO:0007034	vacuolar transport	MODIFY	yes	GO:0071985 multivesicular body sorting pathway	Vacuolar transport is too broad; if retained for CHMP4C it should be framed as general MVB sorting context, not core CHMP4C checkpoint function.
human	CHMP5	IPR005024	GO:0007034	vacuolar transport	MODIFY	yes	GO:0071985 multivesicular body sorting pathway	The conserved ESCRT biology is cargo sorting into MVBs followed by lysosomal delivery, not generic vacuolar transport.
human	CHMP6	IPR005024	GO:0007034	vacuolar transport	MODIFY	yes	GO:0071985 multivesicular body sorting pathway; GO:1902774 late endosome to lysosome transport	CHMP6 should be curated to the specific human endosomal MVB sorting and late endosome-to-lysosome transport terms.
human	CHMP7	IPR005024	GO:0007034	vacuolar transport	MODIFY	yes	GO:0071985 multivesicular body sorting pathway; GO:1902774 late endosome to lysosome transport	CHMP7 has an older supported endosomal-sorting phenotype, but vacuole wording is less appropriate for human curation than MVB sorting / late endosome-to-lysosome transport.
human	CHRAC1	IPR009072	GO:0046982	protein heterodimerization activity	ACCEPT	no		Heterodimerization with POLE3 is a core biochemical property of CHRAC1. The CHRAC1-POLE3 heterodimer is analogous to the H2A-H2B histone dimer and is essential for DNA binding and interaction with the ACF complex.
human	CLCN7	IPR001807,IPR002249	GO:0006821	chloride transport	KEEP_AS_NON_CORE	yes		This term is a high-level parent consistent with ClC-7 function but is superseded by the more specific chloride transmembrane transport and chloride:proton antiporter terms already annotated.
human	CLCN7	IPR001807	GO:0015108	chloride transmembrane transporter activity	KEEP_AS_NON_CORE	yes		Correct but generic; the specific chloride:proton antiporter activity (GO:0062158) is the informative molecular-function term. Retained as non-core.
human	CLCN7	IPR001807,IPR002249	GO:0016020	membrane	MARK_AS_OVER_ANNOTATED	yes		"""membrane"" is an uninformatively broad cellular-component term; the specific lysosomal membrane localization is already captured by experimental annotations."
human	CLCN7	IPR001807	GO:0055085	transmembrane transport	KEEP_AS_NON_CORE	yes		A high-level parent of the specific chloride transmembrane transport term; consistent with ClC-7 function but uninformative on its own. Retained as non-core.
human	CLCN7	IPR002249	GO:0062158	chloride:proton antiporter activity	ACCEPT	no		This is the verified core molecular function and is independently supported by direct electrophysiological measurement of 2Cl(-)/1H(+) exchange.
human	CLGN	IPR001580	GO:0006457	protein folding	ACCEPT	no		Agrees with the experimentally supported IBA annotation; calmegin assists folding of nascent client proteins.
human	CLPS	IPR047576	GO:0035473	lipase binding	ACCEPT	no		Core molecular function, extensively characterized.
human	CLPSL1	IPR001981	GO:0007586	digestion	ACCEPT	no		KEEP_AS_NON_CORE
human	CLPSL1	IPR001981	GO:0008047	enzyme activator activity	ACCEPT	no		Putative core function.
human	CLPSL1	IPR001981	GO:0016042	lipid catabolic process	ACCEPT	no		KEEP_AS_NON_CORE
human	CLPSL2	IPR001981	GO:0007586	digestion	ACCEPT	no		Homology-based annotation.
human	CLPSL2	IPR001981	GO:0008047	enzyme activator activity	ACCEPT	no		Putative core function.
human	CLPSL2	IPR001981	GO:0016042	lipid catabolic process	ACCEPT	no		Core predicted function.
human	CLPX	IPR003959,IPR004487	GO:0005524	ATP binding	ACCEPT	no		Redundant with the IBA ATP binding annotation but correct; ATP binding is core to CLPX function.
human	CLPX	IPR004487	GO:0006457	protein folding	MARK_AS_OVER_ANNOTATED	yes		ClpX actively unfolds and translocates substrates rather than promoting folding; this generic InterPro BP transfer is an over-annotation. Its chaperone role is better captured by the ATP-dependent protein folding chaperone MF term and by protein quality control / heme biosynthesis process terms.
human	CLPX	IPR004487	GO:0140662	ATP-dependent protein folding chaperone	ACCEPT	no		"This MF term best captures the ATP-dependent chaperone activity of CLPX, including its CLPP-independent remodeling/activation role; it is preferable to the generic ""protein folding"" BP transfer."
human	CLTC	IPR015348,IPR016025	GO:0005198	structural molecule activity	ACCEPT	no		Appropriate molecular function annotation. The primary activity of clathrin heavy chain is structural - providing the scaffold for vesicle formation. This is complementary to more specific binding functions.
human	CLTC	IPR000547,IPR015348,IPR016025	GO:0006886	intracellular protein transport	ACCEPT	no		Appropriate parent term for clathrin's trafficking functions. While more specific terms exist (receptor-mediated endocytosis, retrograde transport), this captures the general role in vesicular transport.
human	CLTC	IPR000547,IPR015348,IPR016025,IPR016341	GO:0016192	vesicle-mediated transport	ACCEPT	no		Appropriate parent term for clathrin's transport functions. This captures the general role in vesicle-based trafficking.
human	CLTC	IPR015348,IPR016025	GO:0030130	clathrin coat of trans-Golgi network vesicle	ACCEPT	no		Core localization for TGN function. This is a well-established site of clathrin coat formation distinct from plasma membrane CME.
human	CLTC	IPR015348,IPR016025	GO:0030132	clathrin coat of coated pit	ACCEPT	no		Core cellular component. This is precisely where clathrin performs its primary structural function during endocytosis.
human	CLTC	IPR016341	GO:0032051	clathrin light chain binding	ACCEPT	no		Core molecular function. IEA annotation is consistent with IBA evidence.
human	CLTC	IPR016341	GO:0071439	clathrin complex	ACCEPT	no		Core cellular component. IEA annotation is consistent with IBA evidence.
human	CNOT4	IPR003954,IPR035979	GO:0003676	nucleic acid binding	MARK_AS_OVER_ANNOTATED	yes		Generic nucleic acid binding is the uninformative parent of RNA binding; CNOT4 has an RRM and is captured as an mRNA-bound protein, so RNA binding (GO:0003723) is the appropriate specific term. DNA binding is not supported.
human	CNOT4	IPR000504	GO:0003723	RNA binding	KEEP_AS_NON_CORE	yes		RNA binding is supported by an RRM domain and orthogonal HDA evidence (PMID:22681889), but is not the characterized core molecular function of CNOT4.
human	CNOT4	IPR039780	GO:0004842	ubiquitin-protein transferase activity	ACCEPT	no		CNOT4 is an experimentally confirmed E3 ubiquitin transferase; the InterPro transfer is concordant with direct evidence.
human	CNOT4	IPR039780	GO:0030014	CCR4-NOT complex	ACCEPT	no		CCR4-NOT complex membership is real and corroborated by NAS and IDA evidence, though the association is peripheral/transient in human cells.
human	CNOT4	IPR000571	GO:0046872	metal ion binding	MARK_AS_OVER_ANNOTATED	yes	GO:0008270 zinc ion binding	Metal ion binding is the uninformative parent of zinc ion binding; CNOT4 specifically coordinates zinc via its RING/zinc-finger domains, so GO:0008270 would be more appropriate.
human	COMP	IPR001881,IPR003367,IPR008859,IPR018097,IPR028974	GO:0005509	calcium ion binding	ACCEPT	no		This annotation is well-supported by multiple experimental studies demonstrating calcium binding by COMP. The InterPro EGF-Ca-binding domains (IPR001881) correctly predict this function, validated by direct experimental evidence.
human	COPG1	IPR013040,IPR037067	GO:0005198	structural molecule activity	ACCEPT	no		COPG1's primary molecular function is structural - it is an essential subunit of the COPI coat that contributes to coat assembly, membrane curvature, and vesicle formation. This is appropriate as a high-level MF term.
human	COPG1	IPR002553,IPR009028,IPR013040,IPR037067	GO:0006886	intracellular protein transport	ACCEPT	no		COPI mediates intracellular protein transport, specifically retrograde transport from Golgi to ER. This general annotation is correct.
human	COPG1	IPR002553,IPR009028	GO:0030117	membrane coat	ACCEPT	no		Correct as a more general cellular component annotation. COPG1 is part of the COPI membrane coat.
human	COPG1	IPR013040,IPR037067	GO:0030126	COPI vesicle coat	ACCEPT	no		Correct and consistent with IBA annotation. Core localization for COPG1.
human	COPG2	IPR013040,IPR037067	GO:0005198	structural molecule activity	ACCEPT	no		"COPG2's primary molecular function is structural - it is an essential subunit of the COPI coat that contributes to coat assembly, membrane curvature, and vesicle formation. The deep research confirms it is ""not an enzyme or transporter"" but ""a structural component."""
human	COPG2	IPR002553,IPR009028,IPR013040,IPR037067	GO:0006886	intracellular protein transport	ACCEPT	no		COPI mediates intracellular protein transport, specifically retrograde transport from Golgi to ER. This general annotation is correct.
human	COPG2	IPR002553,IPR009028	GO:0030117	membrane coat	ACCEPT	no		Correct as a more general cellular component annotation. COPG2 is part of the COPI membrane coat.
human	COPG2	IPR013040,IPR037067	GO:0030126	COPI vesicle coat	ACCEPT	no		Correct and consistent with IBA annotation. Core localization for COPG2.
human	COPS8	IPR033205	GO:0000338	protein deneddylation	ACCEPT	no		The CSN complex functions as the major deneddylase in cells. COPS8 is required for proper CSN complex assembly and therefore contributes to the deneddylation process, even though it does not contain the catalytic metalloprotease domain (found in CSN5).
human	COPS8	IPR033205	GO:0010387	COP9 signalosome assembly	ACCEPT	no		CSN8 is essential for proper CSN complex assembly. Studies show that reduced CSN8 levels lead to holocomplex destabilization and formation of aberrant subcomplexes.
human	COX10	IPR006369,IPR016315	GO:0006783	heme biosynthetic process	KEEP_AS_NON_CORE	yes		Keep as non-core because GO:0006784 is the more precise process.
human	COX10	IPR000537,IPR006369	GO:0016020	membrane	KEEP_AS_NON_CORE	yes		Keep as non-core; mitochondrial inner/mitochondrial membrane terms are more informative.
human	COX10	IPR000537	GO:0016765	transferase activity, transferring alkyl or aryl (other than methyl) groups	KEEP_AS_NON_CORE	yes		Keep as non-core because the specific GO:0008495 activity is present.
human	COX15	IPR003780,IPR023754	GO:0016020	membrane	KEEP_AS_NON_CORE	yes		Keep as non-core; mitochondrial inner membrane is the informative localization.
human	COX4I1	IPR004203,IPR036639	GO:0006123	mitochondrial electron transport, cytochrome c to oxygen	ACCEPT	no		Redundant with IBA annotation but correctly inferred from domain composition. The COX4 domain family (Pfam PF02936) is specific to cytochrome c oxidase subunit IV, making this IEA inference sound.
human	COX4I2	IPR004203,IPR036639	GO:0006123	mitochondrial electron transport, cytochrome c to oxygen	ACCEPT	no		Correct complex-level biological-process annotation for a bona fide Complex IV subunit. This should not be interpreted as COX4I2 independently enabling cytochrome-c oxidase activity.
human	COX4I2	IPR036639	GO:0045277	respiratory chain complex IV	ACCEPT	no		Core complex-membership annotation. COX4I2 should be represented as part_of respiratory chain Complex IV, while catalytic activity remains attributable to the intact complex and the mtDNA-encoded catalytic core.
human	COX5B	IPR002124,IPR036972	GO:0005740	mitochondrial envelope	MODIFY	yes	GO:0005743 mitochondrial inner membrane	While technically correct (inner membrane is part of envelope), this term is too general. More specific term GO:0005743 (mitochondrial inner membrane) better captures COX5B's precise localization and is already annotated with stronger evidence.
human	COX5B	IPR002124,IPR036972	GO:0006123	mitochondrial electron transport, cytochrome c to oxygen	ACCEPT	no		Same biological process as IBA annotation, just from different evidence source (InterPro domain mapping). Acceptable redundancy.
human	COX5B	IPR036972	GO:0045277	respiratory chain complex IV	ACCEPT	no		Core and precise cellular component annotation. COX5B is integral structural component of Complex IV, incorporated during assembly and required for complex stability. Multiple structural studies confirm this.
human	COX6B1	IPR003213,IPR036549	GO:0005739	mitochondrion	ACCEPT	no		Correct broad localization.
human	CREB1	IPR001630,IPR003102,IPR004827,IPR046347	GO:0006355	regulation of DNA-templated transcription	ACCEPT	no		Accurate general annotation inferred from InterPro domains. More specific annotations (GO:0006357, GO:0045944) provide better detail.
human	CRMP1	IPR006680	GO:0016787	hydrolase activity	REMOVE	yes		Domain/phylogenetic over-propagation refutable on biological grounds: the metal-cofactor-binding residues are absent (UniProt CAUTION), so no metallo-hydrolase activity is supported; the real function is a non-catalytic cytoskeletal regulator. Same basis as the DPYSL5 review.
human	CRMP1	IPR011059	GO:0016810	hydrolase activity, acting on carbon-nitrogen (but not peptide) bonds	REMOVE	yes		Domain/phylogenetic over-propagation refutable on biological grounds: the metal-cofactor-binding residues are absent (UniProt CAUTION), so no metallo-hydrolase activity is supported; the real function is a non-catalytic cytoskeletal regulator. Same basis as the DPYSL5 review.
human	CSNK1D	IPR000719,IPR017441	GO:0005524	ATP binding	ACCEPT	no		Essential for catalysis; supported by InterPro kinase domain signatures and over 30 PDB structures of the ATP-binding site.
human	CSNK2B	IPR000704,IPR016149,IPR035991	GO:0005956	protein kinase CK2 complex	ACCEPT	no		Direct structural and biochemical evidence places CSNK2B as the regulatory subunit bridging the two catalytic subunits in the CK2 holoenzyme.
human	CSNK2B	IPR000704,IPR016149,IPR035991	GO:0019887	protein kinase regulator activity	ACCEPT	no		CSNK2B is the prototypical protein kinase regulatory subunit; this term captures its central non-catalytic function within the holoenzyme.
human	CTBP1	IPR043322	GO:0003714	transcription corepressor activity	ACCEPT	no		IEA annotation for transcription corepressor activity is redundant with the IBA (index 1) but correct. CTBP1 is well established as a transcriptional corepressor.
human	CTBP1	IPR006139,IPR043322	GO:0016616	oxidoreductase activity, acting on the CH-OH group of donors, NAD or NADP as acceptor	ACCEPT	no		Correct IEA annotation consistent with the IDA annotation from PMID:12419229. CTBP1 has demonstrated dehydrogenase activity with NAD as cofactor.
human	CTBP1	IPR006139,IPR006140,IPR043322	GO:0051287	NAD binding	ACCEPT	no		NAD binding is well established for CTBP1. Its Rossmann fold binds NAD+/NADH, which allosterically regulates oligomerization and corepressor function. Supported by crystal structure (PMID:12419229).
human	CTLA4	IPR008096	GO:0006955	immune response	ACCEPT	no		Broad but accurate IEA. More specific terms provide the detail. The InterPro mapping from the CTLA4 domain correctly identifies immune function.
human	CTLA4	IPR008096	GO:0016020	membrane	ACCEPT	no		Very broad but correct. CTLA4 is a transmembrane protein. More specific membrane localizations are captured by other annotations.
human	CTLA4	IPR040216	GO:0042129	regulation of T cell proliferation	ACCEPT	no		"Correct. CTLA4 is a major regulator (specifically negative regulator) of T cell proliferation. The broader ""regulation"" term is acceptable for an InterPro-derived IEA since the family includes both CD28 (positive) and CTLA4 (negative)."
human	CUL3	IPR001373,IPR016157	GO:0006511	ubiquitin-dependent protein catabolic process	ACCEPT	no		Proteasome-mediated ubiquitin-dependent catabolism is a canonical proximal output for many CRL3 substrate-adaptor complexes, while non-degradative ubiquitination remains a caveat for some substrates.
human	CUL3	IPR001373,IPR016157	GO:0031625	ubiquitin protein ligase binding	MODIFY	yes	GO:0160072 ubiquitin ligase complex scaffold activity	The evidence supports CUL3 as the scaffold component of CRL3 ligase complexes; ubiquitin protein ligase binding is a lower-information proxy. The CRL3 complex cellular-component annotation should be handled separately rather than used as an MF replacement.
human	CWC27	IPR020892	GO:0006457	protein folding	MARK_AS_OVER_ANNOTATED	yes		"CWC27 is a demonstrated catalytically inactive pseudo-PPIase: it shows no peptidyl-prolyl cis-trans isomerase activity and no cyclosporin binding, and UniProt curates it as a ""Probable inactive peptidyl-prolyl cis-trans isomerase"" with a CAUTION. The InterPro2GO ""protein folding"" transfer ignores the loss of catalytic residues and therefore over-annotates a foldase/chaperone function that CWC27 does not possess. There is no evidence CWC27 catalyzes or assists protein folding."
human	CYB5R4	IPR001433,IPR017927	GO:0016491	oxidoreductase activity	MARK_AS_OVER_ANNOTATED	yes		This is a high-level parent of the specific cytochrome-b5 reductase activity that is already annotated; it is correct but too general to be informative.
human	CYB5R4	IPR018506	GO:0020037	heme binding	ACCEPT	no		Heme binding is experimentally established and the protein has a cytochrome b5-like heme-binding domain with axial His ligands.
human	CYC1	IPR002326,IPR036909	GO:0009055	electron transfer activity	ACCEPT	no		InterPro mapping of the Cyt_c1 domain to electron transfer activity is biophysically and structurally accurate. Falcon documents the edge-to-edge geometry (~9.4 Å) and tunneling rates consistent with single-electron transfer.
human	CYC1	IPR002326,IPR036909	GO:0020037	heme binding	ACCEPT	no		"Defining feature of the cytochrome c1 fold. Falcon: cytochrome c1 contains ""a **single c-type heme, heme c1**, covalently attached and exposed for rapid electron transfer to cytochrome c."""
human	CYCS	IPR002327,IPR009056,IPR036909	GO:0009055	electron transfer activity	ACCEPT	no		Correct and consistent with the IBA annotation. The cytochrome c domain family is defined by its electron transfer function.
human	CYCS	IPR002327,IPR009056,IPR036909	GO:0020037	heme binding	ACCEPT	no		Heme binding is a core molecular function of cytochrome c. The heme c group is covalently attached and is essential for electron transfer activity.
human	DDA1	IPR033575	GO:0032434	regulation of proteasomal ubiquitin-dependent protein catabolic process	ACCEPT	no		Correct; as a stabilizing subunit DDA1 promotes efficient CRL4-mediated ubiquitination and subsequent proteasomal degradation of substrates.
human	DDB1	IPR004871	GO:0003676	nucleic acid binding	REMOVE	yes		DDB1 is the adaptor/scaffold subunit of UV-DDB and the DCX(DDB1-CUL4) ligases; it does not itself bind nucleic acid. Direct lesion/DNA contact in UV-DDB is made by the DDB2 subunit. This InterPro2GO electronic mapping (GO_REF:0000002) is a false-positive attribution of a DNA-binding function to the wrong subunit and should be removed.
human	DDB2	IPR033312	GO:0003684	damaged DNA binding	ACCEPT	no		Correct core molecular function; redundant with IDA/IBA/TAS evidence.
human	DDB2	IPR033312	GO:0080008	Cul4-RING E3 ubiquitin ligase complex	ACCEPT	no		Core complex membership; DDB2 is the substrate-recognition (DCAF) module of CRL4(DDB2); redundant with EXP/IMP evidence.
human	DENR	IPR001950,IPR005873,IPR036877	GO:0003743	translation initiation factor activity	ACCEPT	no		The eIF2D-like (re)initiation-factor activity is experimentally established for the MCTS1-DENR complex; DENR is an essential subunit. This is a core molecular function.
human	DENR	IPR001950,IPR036877	GO:0006413	translational initiation	KEEP_AS_NON_CORE	yes		Correct parent process but less informative than the specific reinitiation role; retained as non-core.
human	DHCR24	IPR006094,IPR036318	GO:0050660	flavin adenine dinucleotide binding	ACCEPT	no		DHCR24 is a FAD-dependent oxidoreductase with a conserved FAD-binding domain. Addition of FAD increases enzymatic activity twofold, suggesting noncovalent FAD binding [PMID:11519011].
human	DHCR24	IPR016166	GO:0071949	FAD binding	ACCEPT	no		Duplicate of GO:0050660 but accurate. DHCR24 requires FAD as a cofactor for its oxidoreductase activity [PMID:11519011].
human	DHODH	IPR005720	GO:0005737	cytoplasm	REMOVE	yes		This annotation is misleading. While technically mitochondria are in the cytoplasm, GO:0005737 (cytoplasm) implies cytosolic localization which is incorrect. DHODH is an integral inner mitochondrial membrane protein. The more specific term GO:0005743 (mitochondrial inner membrane) is already annotated and is the appropriate localization term.
human	DHODH	IPR001295,IPR005719	GO:0006207	'de novo' pyrimidine nucleobase biosynthetic process	ACCEPT	no		Correct biological process annotation with independent computational evidence supporting the IBA annotation.
human	DHODH	IPR005719	GO:0016020	membrane	MARK_AS_OVER_ANNOTATED	yes		While technically correct (DHODH is a membrane protein), this term is uninformatively general. The specific localization GO:0005743 (mitochondrial inner membrane) is already correctly annotated. This adds no additional information and clutters the annotation set.
human	DHODH	IPR001295,IPR005720	GO:0016627	oxidoreductase activity, acting on the CH-CH group of donors	MARK_AS_OVER_ANNOTATED	yes		Correct but uninformatively general. The specific enzyme activity GO:0106430 (dihydroorotate dehydrogenase (quinone) activity) or GO:0004152 provides much more useful information. This intermediate-level term adds little value.
human	DLX1	IPR017970	GO:0006355	regulation of DNA-templated transcription	ACCEPT	no		This is a valid but more general annotation than GO:0006357. Both terms are in the transcription regulation hierarchy. The more specific RNA pol II term is preferable, but this general term is not incorrect and can be retained.
human	DNAJA2	IPR012724	GO:0005524	ATP binding	REMOVE	yes		DnaJ/HSP40 co-chaperones do not bind ATP themselves. They stimulate the ATPase activity of HSP70 proteins, but it is the HSP70 partner (e.g., HSPA1A/B) that binds and hydrolyzes ATP. DNAJA2 has no known ATP binding site. The InterPro mapping from IPR012724 (DnaJ) to GO:0005524 (ATP binding) is misleading for this protein family. UniProt does not annotate DNAJA2 with ATP binding activity.
human	DNAJA2	IPR012724	GO:0009408	response to heat	ACCEPT	no		Response to heat is a legitimate biological process for DNAJA2 as an HSP40 co-chaperone. The more specific GO:0034605 (cellular response to heat) is annotated by IBA. The IEA annotation of the broader parent term GO:0009408 is acceptable and consistent.
human	DNAJA2	IPR044713	GO:0030544	Hsp70 protein binding	ACCEPT	no		Hsp70 protein binding is experimentally demonstrated for DNAJA2 (PMID:21231916, PMID:24318877). The InterPro mapping from IPR044713 is correct. While GO:0051087 (protein-folding chaperone binding) is also annotated and captures the functional context, GO:0030544 specifically captures the HSP70-binding aspect and is technically accurate.
human	DNAJA2	IPR001305	GO:0031072	heat shock protein binding	MARK_AS_OVER_ANNOTATED	yes		Heat shock protein binding is correct for DNAJA2 as it binds HSP70 chaperones. The more specific GO:0030544 (Hsp70 protein binding) is also annotated from IEA. Retaining the broader parent term as a core accepted annotation would obscure the more informative Hsp70-specific binding annotation.
human	DNAJA2	IPR001305,IPR008971,IPR012724	GO:0051082	unfolded protein binding	MODIFY	yes	GO:0044183 protein folding chaperone	GO:0051082 is being obsoleted per go-ontology#30962. The InterPro-based inference correctly identifies DNAJA2 as having DnaJ domains with substrate binding capacity, but the term conflates binding with the active chaperone function. DNAJA2 functions as a protein folding chaperone in the HSP70 foldase pathway. GO:0044183 (protein folding chaperone) is the correct replacement.
human	DNAJA4	IPR012724	GO:0005524	ATP binding	REMOVE	yes		J-domain proteins like DNAJA4 do not bind ATP themselves. The J-domain stimulates the ATPase activity of HSP70 partners, but it is the HSP70 that binds ATP, not the co-chaperone. This IEA annotation based on the DnaJ InterPro domain is an incorrect transitive inference.
human	DNAJA4	IPR012724	GO:0009408	response to heat	ACCEPT	no		Response to heat is an appropriate broad annotation for a heat shock co-chaperone. The more specific child term cellular response to heat (GO:0034605) is already annotated by IBA. This broader IEA is acceptable.
human	DNAJA4	IPR044713	GO:0030544	Hsp70 protein binding	ACCEPT	no		Hsp70 protein binding is correct -- DNAJA4 binds HSP70 partners via its J-domain. While the more informative term protein-folding chaperone binding (GO:0051087) is already annotated, this IEA is not incorrect and reflects the InterPro domain-based inference.
human	DNAJA4	IPR001305	GO:0031072	heat shock protein binding	MARK_AS_OVER_ANNOTATED	yes		Heat shock protein binding is correct for DNAJA4 as it binds HSP70 chaperones. The more specific GO:0030544 (Hsp70 protein binding) is also annotated from IEA, and GO:0051087 captures the functional chaperone-binding context. Retaining this broader parent term as accepted would obscure the more informative Hsp70-specific and chaperone-binding annotations.
human	DNAJA4	IPR001305,IPR008971,IPR012724	GO:0051082	unfolded protein binding	MODIFY	yes	GO:0044183 protein folding chaperone	GO:0051082 is being obsoleted. The InterPro-based annotation correctly identifies DNAJA4 as having substrate-binding domains characteristic of J-domain protein co-chaperones, but the term should be replaced with GO:0044183 (protein folding chaperone) which properly captures the functional role of binding client proteins to assist in the protein folding process.
human	DNAJB1	IPR008971	GO:0051082	unfolded protein binding	MODIFY	yes	GO:0044183 protein folding chaperone	GO:0051082 is scheduled for obsoletion (go-ontology#30962). This IEA annotation derives from the InterPro domain mapping (IPR008971, HSP40/DnaJ peptide-binding domain). The InterPro2GO mapping will need to be updated when GO:0051082 is obsoleted. For DNAJB1 specifically, the correct replacement is GO:0044183 (protein folding chaperone), since DNAJB1 is a foldase-type J-domain protein that promotes protein refolding in concert with HSP70 (PMID:21231916).
human	DNAJB11	IPR008971	GO:0006457	protein folding	KEEP_AS_NON_CORE	yes		Protein folding is a downstream process outcome of ERdj3's BiP co-chaperone activity; the direct molecular roles are BiP ATPase stimulation and substrate binding.
human	DNAJB13	IPR008971	GO:0006457	protein folding	KEEP_AS_NON_CORE	yes		Domain-based prediction; not demonstrated for DNAJB13 whose core role is structural in the radial spoke.
human	DNAJB2	IPR043183	GO:0030544	Hsp70 protein binding	ACCEPT	no		The InterPro-derived IEA annotation to Hsp70 protein binding is accurate for DNAJB2 as a J-domain protein. This is experimentally validated (PMID:7957263, PMID:22219199) and represents a core molecular function.
human	DNAJB2	IPR043183	GO:0051082	unfolded protein binding	MODIFY	yes	GO:0044183 protein folding chaperone	GO:0051082 is being obsoleted. The IEA annotation from InterPro (IPR043183) correctly identifies DNAJB2 as having a DNJB2/6-like domain associated with chaperone function, but the target term should be updated to GO:0044183 (protein folding chaperone), which better captures the co-chaperone role of J-domain proteins in assisting protein folding.
human	DNAJB4	IPR008971	GO:0006457	protein folding	KEEP_AS_NON_CORE	yes		Same downstream process rationale as the IBA protein folding annotation; DNAJB4 assists rather than autonomously catalyzes folding.
human	DNAJB5	IPR008971	GO:0006457	protein folding	KEEP_AS_NON_CORE	yes		Same downstream-process rationale as the IBA protein folding annotation; DNAJB5 assists rather than autonomously catalyzes folding.
human	DNAJB6	IPR043183	GO:0030544	Hsp70 protein binding	ACCEPT	no		Hsp70 binding is the fundamental co-chaperone activity of all J-domain proteins. DNAJB6 binds Hsp/c70 via its N-terminal J-domain (PMID:10954706). The InterPro mapping is accurate. While GO:0051087 (protein-folding chaperone binding) is a parent term also annotated, GO:0030544 is more specific to the Hsp70 interaction and is a valid annotation.
human	DNAJB6	IPR043183	GO:0051082	unfolded protein binding	MODIFY	yes	GO:0044183 protein folding chaperone	GO:0051082 is being obsoleted per go-ontology#30962. The IEA mapping from InterPro IPR043183 correctly identifies DNAJB6 as a J-domain protein that interacts with unfolded clients, but the term itself is being retired. DNAJB6 functions as a holdase rather than a foldase (PMID:21231916), so GO:0044183 (protein folding chaperone) is proposed as an interim replacement, acknowledging that a holdase-specific term would better represent the actual molecular activity.
human	DNAJB8	IPR043183	GO:0030544	Hsp70 protein binding	ACCEPT	no		Hsp70 binding is the canonical function of J-domain proteins. DNAJB8 has a well-characterized J-domain (UniProt domain annotation, residues 3-69) and IPI evidence from PMID:21231916 confirms physical interaction with three Hsp70 family members. The InterPro-based IEA inference from IPR043183 is correct and specific. Hageman et al. (PMID:20159555) further showed that while the antiaggregation activity of DNAJB8 is largely J-domain independent, the J-domain still mediates Hsp70 interaction.
human	DNAJB8	IPR043183	GO:0051082	unfolded protein binding	MODIFY	yes	GO:0044183 protein folding chaperone	GO:0051082 is being obsoleted. The InterPro-based IEA mapping from IPR043183 correctly identified that DNAJB8 interacts with unfolded substrates, but GO:0044183 (protein folding chaperone) is the recommended replacement that better captures the functional chaperone activity. DNAJB8 already has GO:0044183 annotations from both IBA and IDA evidence. Caveat: DNAJB8 functions as a holdase rather than a foldase -- it suppresses aggregation rather than promoting productive folding -- but GO currently lacks a dedicated holdase term.
human	DNAJC10	IPR021170	GO:0034975	protein folding in endoplasmic reticulum	ACCEPT	no		Direct evidence shows ERdj5 is required for efficient folding of obligatory-non-native-disulfide clients such as LDLR.
human	DNAJC13	IPR044978	GO:0007032	endosome organization	ACCEPT	no		Corroborated by direct experimental evidence that loss of DNAJC13/RME-8 alters endosomal tubulation and SNX1 membrane association; a core biological process for this gene.
human	DNAJC13	IPR044978	GO:2000641	regulation of early endosome to late endosome transport	ACCEPT	no		Supported by direct evidence that DNAJC13 controls EGF/EGFR sorting from early endosomes toward the degradative pathway; a genuine process for this gene.
human	DNAJC17	IPR035979	GO:0003676	nucleic acid binding	KEEP_AS_NON_CORE	yes		Correct but generic; RNA binding (the specific child term) is the informative molecular function for this RRM-containing protein.
human	DNAJC17	IPR000504	GO:0003723	RNA binding	ACCEPT	no		DNAJC17 has a bona fide RRM (RNA recognition motif) with a solved RNA-binding-domain structure; RNA binding is a well-justified molecular function.
human	DNAJC21	IPR003604	GO:0003676	nucleic acid binding	MARK_AS_OVER_ANNOTATED	yes		Bare 'nucleic acid binding' is uninformative and inferred only from domain architecture; the experimentally supported RNA binding (GO:0003723) captures the real activity more precisely.
human	DNAJC21	IPR003604	GO:0008270	zinc ion binding	KEEP_AS_NON_CORE	yes		The C2H2 zinc fingers support zinc-ion binding; this is a structural feature rather than the gene's core co-chaperone/ribosome-biogenesis function.
human	DNAJC25	IPR044632	GO:0006457	protein folding	KEEP_AS_NON_CORE	yes		Domain-based IEA for the generic protein-folding process; same rationale as the IBA annotation, a downstream HSP70-assisted process rather than the gene's specific molecular function.
human	DNAJC27	IPR001806,IPR005225	GO:0005525	GTP binding	ACCEPT	no		The N-terminal domain has intact GTP-binding motifs (P-loop) and is classified in the small-GTPase/Rab family; GTP binding is well supported even though hydrolysis is doubtful.
human	DPEP1	IPR000180,IPR008257	GO:0070573	metallodipeptidase activity	ACCEPT	no		This is an accurate and appropriately specific molecular-function term combining the metal-dependence and dipeptidase activity, both of which are directly established for the human enzyme.
human	DPYSL2	IPR011778	GO:0005737	cytoplasm	ACCEPT	no		Correct core localization for a cytoskeleton-associated cytoplasmic protein.
human	DPYSL2	IPR006680	GO:0016787	hydrolase activity	REMOVE	yes		Domain/phylogenetic over-propagation refutable on biological grounds: the metal-cofactor-binding residues are absent (UniProt CAUTION), so no metallo-hydrolase activity is supported; the real function is a non-catalytic cytoskeletal regulator. Same basis as the DPYSL5 review.
human	DPYSL2	IPR011059	GO:0016810	hydrolase activity, acting on carbon-nitrogen (but not peptide) bonds	REMOVE	yes		Domain/phylogenetic over-propagation refutable on biological grounds: the metal-cofactor-binding residues are absent (UniProt CAUTION), so no metallo-hydrolase activity is supported; the real function is a non-catalytic cytoskeletal regulator. Same basis as the DPYSL5 review.
human	DPYSL3	IPR006680	GO:0016787	hydrolase activity	REMOVE	yes		Domain/phylogenetic over-propagation refutable on biological grounds: the metal-cofactor-binding residues are absent (UniProt CAUTION), so no metallo-hydrolase activity is supported; the real function is a non-catalytic cytoskeletal regulator. Same basis as the DPYSL5 review.
human	DPYSL3	IPR011059	GO:0016810	hydrolase activity, acting on carbon-nitrogen (but not peptide) bonds	REMOVE	yes		Domain/phylogenetic over-propagation refutable on biological grounds: the metal-cofactor-binding residues are absent (UniProt CAUTION), so no metallo-hydrolase activity is supported; the real function is a non-catalytic cytoskeletal regulator. Same basis as the DPYSL5 review.
human	DPYSL4	IPR006680	GO:0016787	hydrolase activity	REMOVE	yes		Domain/phylogenetic over-propagation refutable on biological grounds: the metal-cofactor-binding residues are absent (UniProt CAUTION), so no metallo-hydrolase activity is supported; the real function is a non-catalytic cytoskeletal regulator. Same basis as the DPYSL5 review.
human	DPYSL4	IPR011059	GO:0016810	hydrolase activity, acting on carbon-nitrogen (but not peptide) bonds	REMOVE	yes		Domain/phylogenetic over-propagation refutable on biological grounds: the metal-cofactor-binding residues are absent (UniProt CAUTION), so no metallo-hydrolase activity is supported; the real function is a non-catalytic cytoskeletal regulator. Same basis as the DPYSL5 review.
human	DPYSL5	IPR006680	GO:0016787	hydrolase activity	REMOVE	yes		Domain-based electronic over-propagation that should be removed on biological grounds. The annotation rests solely on the fold signature; the catalytic prerequisite (metal-cofactor binding) is demonstrably absent, the curated GO:0004157 (dihydropyrimidinase) is itself NOT-ed, and there is no positive evidence DPYSL5 performs any hydrolysis. Its established function is non-catalytic (negative regulation of dendrite outgrowth). NB: this is not a logical contradiction with the NOT (GO NOT propagates to child terms, not up to parents) - it is an unsupported, biologically implausible over-annotation. A weaker action (MARK_AS_OVER_ANNOTATED) does not fit, since that is for terms the gene is genuinely related to but peripheral on; here the activity is absent.
human	DPYSL5	IPR011059	GO:0016810	hydrolase activity, acting on carbon-nitrogen (but not peptide) bonds	REMOVE	yes		Domain-based over-propagation contradicted on biological grounds by the loss of metal-cofactor-binding residues (UniProt CAUTION). No positive evidence of any C-N hydrolase activity; curated dihydropyrimidinase activity is NOT-ed. Remove, consistent with the GO:0016787 removal.
human	DRG2	IPR005225,IPR006073,IPR006074,IPR031167,IPR045001	GO:0005525	GTP binding	KEEP_AS_NON_CORE	yes		GTP binding is real but the informative core molecular function is GTPase activity; retained as a supporting non-core annotation.
human	EDEM1	IPR001382,IPR036026	GO:0005509	calcium ion binding	KEEP_AS_NON_CORE	yes		Accurate structural cofactor attribute of the GH47 mannosidase-like domain, but not a standalone core function; the informative functions are misfolded protein recognition and ERAD.
human	EDEM1	IPR012341	GO:0005975	carbohydrate metabolic process	MARK_AS_OVER_ANNOTATED	yes		Over-general parent; the specific ER mannose trimming (GO:1904380) and ERAD (GO:0036503) terms better capture the biology.
human	EDEM1	IPR001382,IPR036026	GO:0016020	membrane	MARK_AS_OVER_ANNOTATED	yes	GO:0005789 endoplasmic reticulum membrane	Uninformative parent; EDEM1 is specifically an ER membrane protein.
human	EDEM2	IPR001382,IPR036026	GO:0005509	calcium ion binding	KEEP_AS_NON_CORE	yes		Accurate structural cofactor attribute of the GH47 fold but not a standalone core function; the catalytic mannosidase activity is the informative function.
human	EDEM2	IPR012341	GO:0005975	carbohydrate metabolic process	MARK_AS_OVER_ANNOTATED	yes		Over-general parent; the specific ER mannose trimming (GO:1904380) and glycoprotein ERAD terms better capture the biology.
human	EDEM2	IPR001382,IPR036026	GO:0016020	membrane	MARK_AS_OVER_ANNOTATED	yes	GO:0005788 endoplasmic reticulum lumen	Uninformative and inaccurate parent from a domain-based inference; EDEM2 is a soluble ER lumenal protein, better captured by ER lumen.
human	EDEM2	IPR044674	GO:1904380	endoplasmic reticulum mannose trimming	ACCEPT	no		Correct core biological process; redundant with the IMP annotation from endogenous knockout analysis.
human	EDEM3	IPR001382,IPR036026	GO:0005509	calcium ion binding	KEEP_AS_NON_CORE	yes		Accurate cofactor requirement of the GH47 fold but not a standalone core function; the catalytic mannosidase activity is the informative function.
human	EDEM3	IPR012341	GO:0005975	carbohydrate metabolic process	MARK_AS_OVER_ANNOTATED	yes		Over-general parent; the specific ER mannose trimming (GO:1904380) and glycoprotein ERAD terms better capture the biology.
human	EDEM3	IPR001382,IPR036026	GO:0016020	membrane	MARK_AS_OVER_ANNOTATED	yes	GO:0005788 endoplasmic reticulum lumen	Uninformative and inaccurate parent from a domain-based inference; EDEM3 is a soluble ER lumenal protein, better captured by ER lumen.
human	EEF2K	IPR004166	GO:0004674	protein serine/threonine kinase activity	KEEP_AS_NON_CORE	yes		Directionally correct (it is a Thr-directed kinase) but the generic term both under-specifies and slightly mischaracterizes the alpha-kinase; the core MF is elongation factor-2 kinase activity.
human	EEF2K	IPR017400	GO:0005509	calcium ion binding	KEEP_AS_NON_CORE	yes		Plausible in the context of calcium/calmodulin regulation, but the salient, experimentally supported interaction is with calmodulin; retained as non-core.
human	EEF2K	IPR004166	GO:0005524	ATP binding	ACCEPT	no		ATP is the cosubstrate of the eEF2 kinase reaction (eEF2 + ATP gives eEF2-phosphate + ADP); ATP binding is a supported and necessary molecular function.
human	EGFR	IPR000719,IPR001245,IPR008266	GO:0004672	protein kinase activity	ACCEPT	no		Accurate parent term for the protein tyrosine kinase activity of EGFR.
human	EGFR	IPR016245	GO:0007169	cell surface receptor protein tyrosine kinase signaling pathway	ACCEPT	no		This is the parent pathway term that accurately describes EGFR function.
human	EGFR	IPR016245	GO:0016020	membrane	ACCEPT	no		As a transmembrane receptor, EGFR requires membrane localization for proper protein topology, with the extracellular domain for ligand binding and the intracellular kinase domain for signal transduction.
human	EIF2AK3	IPR000719,IPR008271	GO:0004672	protein kinase activity	MODIFY	yes	GO:0004694 eukaryotic translation initiation factor 2alpha kinase activity	Use the child term that captures PERK's established substrate specificity.
human	EIF2AK3	IPR000719,IPR017441	GO:0005524	ATP binding	MARK_AS_OVER_ANNOTATED	yes		This term is technically true but uninformative for core curation.
human	EIF2D	IPR039757	GO:0001731	formation of translation preinitiation complex	ACCEPT	no		Consistent with EIF2D's documented role in assembling tRNA onto 40S/mRNA complexes.
human	EIF2D	IPR002478	GO:0003723	RNA binding	KEEP_AS_NON_CORE	yes		Correct but generic; the specific informative function is GTP-independent P-site tRNA delivery (initiation factor activity).
human	EIF2D	IPR001950,IPR036877,IPR039757	GO:0003743	translation initiation factor activity	ACCEPT	no		Agrees with direct experimental evidence; core molecular function.
human	EIF2D	IPR001950,IPR036877	GO:0006413	translational initiation	KEEP_AS_NON_CORE	yes		Correct parent process but less informative than the specific GTP-independent (re)initiation/recycling role.
human	EIF4E2	IPR001040,IPR019770	GO:0003723	RNA binding	KEEP_AS_NON_CORE	yes		Correct but subsumed by the specific RNA 7-methylguanosine cap binding annotation.
human	EIF4E2	IPR001040,IPR019770	GO:0003743	translation initiation factor activity	MODIFY	yes	GO:0045182 translation regulator activity	4EHP does not promote initiation; a translation-regulator/repressor MF is correct.
human	EIF4E2	IPR001040,IPR019770	GO:0006413	translational initiation	MARK_AS_OVER_ANNOTATED	yes		4EHP represses cap-dependent initiation; the positive 'translational initiation' involvement is misleading.
human	EIF5A	IPR001884,IPR020189	GO:0003723	RNA binding	KEEP_AS_NON_CORE	yes		RNA binding is documented but generic; the informative function is ribosome binding / elongation factor activity. Retained as a real but non-core capability.
human	EIF5A	IPR001884	GO:0003746	translation elongation factor activity	ACCEPT	no		Correct molecular function, corroborated by stronger IBA and experimental evidence for eIF5A as an elongation factor.
human	EIF5A	IPR001884	GO:0006414	translational elongation	ACCEPT	no		Correct biological process; corroborated by stronger evidence.
human	EIF5A	IPR001884,IPR020189	GO:0043022	ribosome binding	ACCEPT	no		Experimentally validated 80S ribosome binding; central to and supporting the elongation factor mechanism.
human	ELAVL3	IPR003954,IPR035979	GO:0003676	nucleic acid binding	MODIFY	yes	GO:0003723 RNA binding	While technically correct (ELAVL3 does bind nucleic acids), this term is too broad and uninformative. ELAVL3 specifically binds RNA, not DNA, through its three RRM domains. The more specific term GO:0003723 (RNA binding) is already annotated and better represents the actual molecular function.
human	ELAVL3	IPR002343	GO:1990904	ribonucleoprotein complex	ACCEPT	no		This is an appropriate cellular component annotation. ELAVL3 is an RNA-binding protein with RRM domains that forms ribonucleoprotein complexes with its target mRNAs. The deep research notes ELAVL3 binds over 1,100 transcripts in certain contexts, indicating it forms functional RNP complexes. While more specific localization terms could be added (nucleus, cytoplasm), this general RNP complex annotation is correct.
human	ELOB	IPR039049	GO:0006368	transcription elongation by RNA polymerase II	ACCEPT	no		Accepted. ELOB is a regulatory Elongin subunit in the Elongin ABC transcription elongation factor that promotes RNA polymerase II elongation.
human	ELOB	IPR039049	GO:0030891	VCB complex	ACCEPT	no		Correct. ELOB/ELOC form the Elongin BC module in the VHL-containing CRL2/VCB ubiquitin ligase complex.
human	ELOC	IPR001232,IPR016073	GO:0006511	ubiquitin-dependent protein catabolic process	ACCEPT	no		Accepted as a pathway-level consequence. ELOC-containing CRL2/CRL5 complexes target substrates for ubiquitination and downstream proteasomal degradation.
human	ELOVL5	IPR033677	GO:0005783	endoplasmic reticulum	ACCEPT	no		The broader ER term is acceptable as redundant with the more specific ER membrane annotation. Both are well-supported.
human	ELOVL5	IPR033677	GO:0019367	fatty acid elongation, saturated fatty acid	KEEP_AS_NON_CORE	yes		As noted above, ELOVL5 can act on saturated substrates but this is not its primary function. Same assessment as IBA annotation.
human	EMC1	IPR026895	GO:0072546	EMC complex	ACCEPT	no		Correct; EMC1 is a defining EMC subunit, redundant with stronger evidence.
human	EMC3	IPR002809,IPR008568	GO:0016020	membrane	KEEP_AS_NON_CORE	yes		Correct but generic; the specific ER membrane term captures the informative localization.
human	EMC6	IPR008504	GO:0005783	endoplasmic reticulum	KEEP_AS_NON_CORE	yes		Correct compartment but a parent of the more precise ER membrane term; redundant with experimental ER membrane evidence.
human	EMC6	IPR008504	GO:0016020	membrane	KEEP_AS_NON_CORE	yes		Correct but generic; the specific ER membrane term captures the informative localization.
human	EMC6	IPR008504	GO:0072546	EMC complex	ACCEPT	no		Correct core structural identity; redundant with IDA/IBA evidence.
human	EMC7	IPR013784	GO:0030246	carbohydrate binding	MARK_AS_OVER_ANNOTATED	yes		Fold-similarity-only IEA with no supporting evidence that EMC7 actually binds carbohydrate; the beta-sandwich is structural and serves complex architecture.
human	EMC8	IPR005366	GO:0072546	EMC complex	ACCEPT	no		Correct core membership; redundant with IDA/IPI/IBA evidence for EMC complex membership.
human	EMC9	IPR005366	GO:0072546	EMC complex	ACCEPT	no		Correct core structural identity; redundant with IDA/IBA evidence.
human	ENDOU	IPR018998,IPR039787	GO:0004521	RNA endonuclease activity	ACCEPT	no		PMID:18936097 provided definitive experimental proof of RNA endonuclease activity through biochemical assays showing Mn2+-dependent cleavage of RNA substrates at specific dinucleotide sequences.
human	ENDOU	IPR020436	GO:0005044	scavenger receptor activity	REMOVE	yes		PMID:18936097 definitively disproved receptor activity and established ENDOU as an RNA endonuclease. No binding or signaling assays support scavenger receptor function.
human	ENDOU	IPR020436	GO:0006955	immune response	MODIFY	yes	GO:0002514 B cell tolerance induction	PMID:24344237 (a mouse study) demonstrated EndoU is a critical regulator of B cell AICD, functioning as a post-transcriptional checkpoint in peripheral B cell tolerance. The broad immune response term should be replaced with the specific term GO:0002514 B cell tolerance induction. This is an ortholog (mouse Endou) finding transferred to the human gene.
human	ENDOU	IPR020436	GO:0030247	polysaccharide binding	REMOVE	yes		REMOVE - No evidence for polysaccharide binding. ENDOU binds RNA (polynucleotide), not polysaccharides. This appears to be a misannotation, possibly from confusion between nucleotides and saccharides.
human	ERG	IPR000418,IPR046328	GO:0003700	DNA-binding transcription factor activity	ACCEPT	no		Correct annotation from InterPro mapping of the ETS domain. The more specific Pol II-specific term is also present via IBA and ISA evidence.
human	ERG	IPR000418	GO:0006355	regulation of DNA-templated transcription	ACCEPT	no		Correct but more general than the Pol II-specific annotation. Acceptable as an IEA annotation.
human	ERG	IPR046328	GO:0006357	regulation of transcription by RNA polymerase II	ACCEPT	no		Correct. Duplicates with different evidence codes are acceptable.
human	ERG	IPR000418,IPR003118	GO:0043565	sequence-specific DNA binding	ACCEPT	no		Well supported by experimental evidence. ERG binds purine-rich sequences with the consensus (C/G)(C/a)GG-AA(G/a)T [PMID:8502479].
human	ERLEC1	IPR045149	GO:0030968	endoplasmic reticulum unfolded protein response	MODIFY	yes	GO:0036503 ERAD pathway	GO:0030968 (ER unfolded protein response) refers to the UPR signaling cascade, not to ERAD per se. ERLEC1 is not a UPR signaling component but rather an ERAD cargo receptor. The correct biological process term is GO:0036503 (ERAD pathway), which is already annotated separately. This IEA annotation likely arises from an overly broad InterPro-to-GO mapping for the OS-9-like domain family.
human	ERLEC1	IPR045149	GO:0036503	ERAD pathway	ACCEPT	no		The ERAD pathway is the core biological process in which ERLEC1 participates. The IEA annotation is correct and well supported by experimental evidence from multiple independent studies.
human	ERLIN1	IPR033294	GO:0005783	endoplasmic reticulum	ACCEPT	no		Correct compartment; redundant with the ER membrane annotations.
human	ERLIN1	IPR033294	GO:0031625	ubiquitin protein ligase binding	ACCEPT	no		Informative molecular function; ERLIN1 recruits E3 ubiquitin ligases to the ERAD complex.
human	ERLIN2	IPR033294	GO:0005783	endoplasmic reticulum	ACCEPT	no		Correct compartment; redundant with the ER membrane annotations.
human	ERLIN2	IPR033294	GO:0031625	ubiquitin protein ligase binding	ACCEPT	no		Informative molecular function; ERLIN2 recruits E3 ubiquitin ligases to the ERAD complex.
human	ERO1A	IPR007266	GO:0034975	protein folding in endoplasmic reticulum	KEEP_AS_NON_CORE	yes		Protein folding in the ER is a process consequence of ERO1A's oxidase activity rather than its direct molecular function; appropriate as a non-core process annotation.
human	ERO1A	IPR007266	GO:0071949	FAD binding	ACCEPT	no		FAD is the documented cofactor with mapped binding sites (PubMed:20834232, PDB 3AHQ/3AHR); FAD binding is integral to the oxidase mechanism.
human	ERO1B	IPR007266	GO:0005783	endoplasmic reticulum	ACCEPT	no		ERO1B is an ER-resident oxidase; directly supported by immunofluorescence and glycosylation evidence.
human	ERO1B	IPR007266	GO:0034975	protein folding in endoplasmic reticulum	KEEP_AS_NON_CORE	yes		Protein folding in the ER is the biological-process consequence of the oxidase activity rather than ERO1B's direct molecular function.
human	ERO1B	IPR007266	GO:0071949	FAD binding	ACCEPT	no		FAD is the documented cofactor (PMID:21091435), integral to the oxidase mechanism; FAD binding residues are mapped.
human	ERP29	IPR011679,IPR016855	GO:0005783	endoplasmic reticulum	ACCEPT	no		Correct compartment for this ER-resident chaperone.
human	ERP29	IPR012883	GO:0009306	protein secretion	KEEP_AS_NON_CORE	yes		ERP29 facilitates secretory-protein processing/trafficking, so a protein-secretion process annotation is reasonable but is a downstream consequence of its chaperone function rather than a direct molecular activity.
human	FAS	IPR008063	GO:0004888	transmembrane signaling receptor activity	ACCEPT	no		Correct general molecular function for membrane-bound FAS. This IEA based on InterPro domain mapping is appropriate. Note: Does not apply to soluble isoforms 2-6 which lack the transmembrane domain.
human	FAS	IPR008063	GO:0006955	immune response	ACCEPT	no		While overly broad, FAS does function in immune response contexts. The term encompasses FAS roles in lymphocyte homeostasis, peripheral tolerance, and immune response termination. IEA from InterPro mapping is acceptable.
human	FAS	IPR000488,IPR008063	GO:0007165	signal transduction	ACCEPT	no		Correct but very general term. FAS is indeed a signal transducing receptor. More specific terms (e.g., Fas signaling pathway, extrinsic apoptotic signaling) better capture its function.
human	FAS	IPR008063	GO:0016020	membrane	ACCEPT	no		Correct but overly general term. More specific terms (plasma membrane, membrane raft) are more informative. IEA from InterPro mapping is appropriate.
human	FBXL18	IPR045627	GO:0031146	SCF-dependent proteasomal ubiquitin-dependent protein catabolic process	ACCEPT	no		Core biological process; directly supported by the experimental demonstration that FBXL18 polyubiquitinates and targets FBXL7 for proteasomal degradation, and by reconstituted SCF^FBXL18-mediated K48 degradation of XPB. Note FBXL18 also performs non-degradative K63 ubiquitination of AKT and PTEN, which this catabolic term does not capture.
human	FBXL5	IPR045808	GO:0006879	intracellular iron ion homeostasis	ACCEPT	no		Correct core biological process; redundant with the experimental IMP/IEP evidence.
human	FBXL6	IPR047922	GO:0019005	SCF ubiquitin ligase complex	ACCEPT	no		FBXL6 has a canonical F-box domain and directly interacts with SKP1 and CUL1, making SCF complex membership the correct core cellular component for an F-box substrate receptor.
human	FBXO21	IPR011722,IPR036623	GO:0003677	DNA binding	REMOVE	yes		This is an over-propagated IEA. FBXO21's UniProt-curated function is purely as the substrate-recognition subunit of an SCF E3 ubiquitin ligase, binding SKP1/CUL1 and substrates (EID1). The DNA binding term derives from an InterPro signature (IPR011722 hemimethylated-DNA-binding/YccV-like, TIGR02097 yccV) detected in the protein's C-terminal region; there is no experimental or curated evidence that FBXO21 binds DNA sequence-specifically or functions in DNA metabolism. The annotation conflates a remote domain-fold match with a molecular function and is biologically misleading for a cytoplasmic/nuclear ubiquitin-ligase adaptor.
human	FBXO30	IPR001293	GO:0008270	zinc ion binding	KEEP_AS_NON_CORE	yes		The TRAF-type zinc finger plausibly binds zinc, but this is a structural attribute of one domain and is subsidiary to the protein's role as an SCF substrate-recognition adaptor; not a standalone core function.
human	FBXO30	IPR031890	GO:0061630	ubiquitin protein ligase activity	MODIFY	yes	GO:1990756 ubiquitin-like ligase-substrate adaptor activity	F-box proteins are substrate-recognition adaptors, not catalytic ligases; the catalytic activity resides in RBX1/RING. The substrate-adaptor activity term better captures FBXO30's molecular function.
human	FBXO40	IPR001293	GO:0008270	zinc ion binding	KEEP_AS_NON_CORE	yes		FBXO40 contains a TRAF-type zinc finger (residues 53-112) that plausibly coordinates zinc, but this is a structural domain attribute subsidiary to its role as an SCF substrate adaptor, not a standalone core molecular function.
human	FBXO40	IPR031890	GO:0061630	ubiquitin protein ligase activity	MODIFY	yes	GO:1990756 ubiquitin-like ligase-substrate adaptor activity	As an F-box substrate receptor, FBXO40 does not itself catalyze ubiquitin transfer (that is the RBX1 RING subunit); its molecular function is better captured as a ubiquitin-like ligase-substrate adaptor. This IEA term is propagated from the InterPro Fbxo30/Fbxo40 signature and over-attributes catalytic ligase activity to the adaptor.
human	FBXO43	IPR047147	GO:0007088	regulation of mitotic nuclear division	MARK_AS_OVER_ANNOTATED	yes		FBXO43 is a meiotic regulator; the mitotic-division annotation is a family-level over-propagation from the FBX5_43 InterPro signature shared with mitotic EMI1.
human	FBXO43	IPR047147	GO:0045835	negative regulation of meiotic nuclear division	ACCEPT	no		Core biological process; redundant with the IBA and experimental support for meiotic arrest via APC/C inhibition.
human	FBXO43	IPR002867	GO:0008270	zinc ion binding	KEEP_AS_NON_CORE	yes		Accurate structural feature of the ZBR domain (important for APC/C inhibition), but a structural attribute subsidiary to the core APC/C-inhibitor function rather than a standalone core function.
human	FBXO43	IPR047147	GO:0045835	negative regulation of meiotic nuclear division	ACCEPT	no		Core biological process; redundant with the IBA and experimental support for meiotic arrest via APC/C inhibition.
human	FBXO5	IPR047147	GO:0007088	regulation of mitotic nuclear division	KEEP_AS_NON_CORE	yes		Correct but generic; subsumed by the more specific APC/C-inhibition annotations.
human	FBXO5	IPR047147	GO:0045835	negative regulation of meiotic nuclear division	KEEP_AS_NON_CORE	yes		Real for the family via APC/C inhibition but non-core for human FBXO5 (the dedicated meiotic CSF inhibitor is the paralog EMI2/FBXO43).
human	FBXO8	IPR000904,IPR035999	GO:0005085	guanyl-nucleotide exchange factor activity	KEEP_AS_NON_CORE	yes		"Supported at the sequence level by a genuine SEC7 domain and a UniProt ""Potential"" GEF function, so not removed; however direct GEF catalysis has not been demonstrated. Falcon-sourced literature indicates the available functional evidence (ARF6 binding via the Sec7 domain, plasma-membrane localization, brefeldin A resistance on FBXO8 loss) is most consistent with a Sec7-like ARF6-interaction module rather than catalytic ARF guanine-nucleotide exchange. The activity therefore remains a predicted/unvalidated molecular function secondary to the documented SCF substrate-receptor role, and is kept as non-core rather than accepted as a core function."
human	FBXO8	IPR000904,IPR035999	GO:0032012	regulation of ARF protein signal transduction	KEEP_AS_NON_CORE	yes		Plausible given the SEC7 domain and predicted ARF-activating function. While the original GOA support is purely electronic, Falcon-sourced literature adds genuine functional context: FBXO8 is reported to bind ARF6 via its Sec7 domain, localize to the plasma membrane, mediate ARF6 ubiquitination, and its loss confers brefeldin A resistance. This strengthens a real link between FBXO8 and ARF6-dependent membrane trafficking/invasion, but the evidence is most consistent with a Sec7-like ARF6-binding module rather than demonstrated GEF catalysis, and it remains peripheral to the core SCF substrate-receptor role, so it is kept as non-core.
human	FBXW5	IPR042508	GO:0080008	Cul4-RING E3 ubiquitin ligase complex	ACCEPT	no		Correct second core complex; FBXW5 is a DWD adaptor of the DCX(FBXW5)/CRL4 complex that ubiquitinates TSC2 (and, in NSCLC, DLC1), supported by IDA evidence.
human	FGFR2	IPR000719,IPR001245,IPR008266	GO:0004672	protein kinase activity	ACCEPT	no		Correct parent term. FGFR2 has documented kinase activity (EC 2.7.10.1). More specific child term annotations also exist.
human	FGFR2	IPR016248	GO:0016020	membrane	ACCEPT	no		Correct but general. More specific annotations (plasma membrane) exist.
human	FOXO1	IPR001766,IPR030456	GO:0006355	regulation of DNA-templated transcription	ACCEPT	no		Correct general annotation for a transcription factor.
human	FTH1	IPR001519	GO:0006826	iron ion transport	MODIFY	yes	GO:0006879 intracellular iron ion homeostasis	FTH1's primary function is iron sequestration/storage within the ferritin shell, not active membrane transport. While iron enters and exits the ferritin cage, this is not a transport function in the GO sense.
human	FTH1	IPR001519	GO:0006879	intracellular iron ion homeostasis	ACCEPT	no		Intracellular iron ion homeostasis accurately describes FTH1's physiological role. The ferritin system maintains iron balance by storing excess iron and releasing it when needed through ferritinophagy.
human	FTH1	IPR001519,IPR008331	GO:0008199	ferric iron binding	ACCEPT	no		Fe3+ binding/storage is central to ferritin function. The IEA annotation is consistent with the IBA annotation and well-supported by experimental evidence.
human	FXN	IPR017789	GO:0006879	intracellular iron ion homeostasis	KEEP_AS_NON_CORE	yes		FXN loss leads to disrupted iron homeostasis and mitochondrial iron accumulation (PMID:18160053). However, iron homeostasis regulation is an indirect consequence of FXN's role in Fe-S cluster assembly rather than a direct molecular function.
human	FXN	IPR002908,IPR036524	GO:0008199	ferric iron binding	MARK_AS_OVER_ANNOTATED	yes		Recent NMR evidence shows FXN binds Fe2+ but not Fe3+ (PMID:29576242). Earlier reports of Fe3+ binding may reflect oxidation of bound Fe2+.
human	FXN	IPR002908,IPR036524	GO:0016226	iron-sulfur cluster assembly	ACCEPT	no		Core biological process for FXN, well supported by multiple studies.
human	FZD7	IPR000539,IPR017981	GO:0016020	membrane	REMOVE	yes		Too general. Plasma membrane annotation is more specific.
human	FZD7	IPR017981	GO:0004888	transmembrane signaling receptor activity	REMOVE	yes		Too general. Wnt receptor activity is more specific.
human	FZD7	IPR000539,IPR017981	GO:0007166	cell surface receptor signaling pathway	REMOVE	yes		Too general. Captured by Wnt signaling pathway annotations.
human	GADD45B	IPR024824	GO:0005634	nucleus	ACCEPT	no		Consistent with IDA-supported annotation from PMID:9827804. InterPro-based inference provides supporting automated evidence for nuclear localization.
human	GADD45B	IPR024824	GO:0051726	regulation of cell cycle	KEEP_AS_NON_CORE	yes		Consistent with IBA annotation. InterPro-based inference supports known GADD45 family function in cell cycle regulation via CRIF1 interaction [PMID:12716909].
human	GADD45G	IPR024824	GO:0051726	regulation of cell cycle	MODIFY	yes	GO:0007095 mitotic G2 DNA damage checkpoint signaling	"MODIFY. GADD45G specifically mediates G2/M cell cycle arrest in response to UV and chemical mutagens by inhibiting cdc2/cyclin B1 kinase activity. A more specific term would be ""mitotic G2 DNA damage checkpoint signaling"" (GO:0007095) or ""negative regulation of G2/M transition of mitotic cell cycle""."
human	GAPDH	IPR006424	GO:0006006	glucose metabolic process	ACCEPT	no		Core metabolic function, part of glycolysis
human	GAPDH	IPR006424,IPR020829,IPR020830,IPR020831	GO:0016620	oxidoreductase activity, acting on the aldehyde or oxo group of donors, NAD or NADP as acceptor	REMOVE	yes		Parent term of GO:0004365, acceptable but redundant
human	GAPDH	IPR006424	GO:0050661	NADP binding	REMOVE	yes		GAPDH uses NAD+ not NADP+, likely incorrect
human	GAPDH	IPR006424,IPR020828	GO:0051287	NAD binding	ACCEPT	no		Essential for catalytic activity, NAD+ is the cofactor
human	GAS6	IPR000294,IPR001881,IPR018097,IPR035972	GO:0005509	calcium ion binding	ACCEPT	no		calcium ion binding is supported as part of the core GAS6-TAM receptor ligand and efferocytosis mechanism.
human	GATA3	IPR016374	GO:0000981	DNA-binding transcription factor activity, RNA polymerase II-specific	ACCEPT	no		This IEA annotation is consistent with the IBA annotation and experimental evidence. While less specific than the IBA, it correctly identifies the core molecular function based on domain architecture. The annotation is accurate but redundant with the more specific IBA annotation above.
human	GATA3	IPR000679,IPR013088	GO:0006355	regulation of DNA-templated transcription	ACCEPT	no		Core function. GATA3 is fundamentally a transcription factor that regulates gene expression. IEA based on InterPro domain annotation is valid and consistent with extensive experimental evidence.
human	GBA1	IPR001139	GO:0006665	sphingolipid metabolic process	MODIFY	yes	GO:0006680 glucosylceramide catabolic process	Replace with glucosylceramide catabolic process, the specific sphingolipid process directly catalyzed by GBA1.
human	GCH1	IPR001474,IPR018234	GO:0046654	tetrahydrofolate biosynthetic process	REMOVE	yes		This is an INCORRECT annotation. GCH1/GTPCH1 catalyzes the first step in tetrahydroBIOPTERIN (BH4) biosynthesis, NOT tetrahydroFOLATE (THF) biosynthesis. While both are pteridines, they are synthesized via different pathways. THF biosynthesis involves dihydrofolate reductase (DHFR), not GTPCH1. This appears to be an erroneous InterPro-based inference that confused these two distinct pteridine pathways.
human	GCLC	IPR014746	GO:0003824	catalytic activity	MODIFY	yes	GO:0004357 glutamate-cysteine ligase activity	This is an overly broad term. The specific catalytic activity (GO:0004357 glutamate-cysteine ligase activity) is already annotated with experimental evidence and should be used instead.
human	GDPD2	IPR017946,IPR030395	GO:0006629	lipid metabolic process	MODIFY	yes	GO:0006650 glycerophospholipid metabolic process	While GDPD2 is involved in lipid metabolism, its specific function is the catabolism of glycerophosphoinositol, a glycerophospholipid derivative. A more specific biological process term would better represent its actual metabolic role.
human	GDPD2	IPR017946,IPR030395	GO:0008081	phosphoric diester hydrolase activity	MODIFY	yes	GO:0047394 glycerophosphoinositol inositolphosphodiesterase activity	GDPD2 does have phosphoric diester hydrolase activity, but experimental characterization has shown it specifically acts on glycerophosphoinositol. Using the more specific molecular function term provides better functional annotation.
human	GET1	IPR028945	GO:0071816	tail-anchored membrane protein insertion into ER membrane	ACCEPT	no		Correct core process; redundant with IDA/IMP/IBA evidence.
human	GET4	IPR007317	GO:0045048	protein insertion into ER membrane	KEEP_AS_NON_CORE	yes		Correct but generic parent term; GET4 functions at the pre-targeting/loading step.
human	GK5	IPR000577,IPR018483,IPR018484,IPR018485	GO:0005975	carbohydrate metabolic process	ACCEPT	no		Metabolic role.
human	GK5	IPR018483	GO:0016773	phosphotransferase activity, alcohol group as acceptor	ACCEPT	no		Specific enzymatic activity.
human	GLA	IPR000111,IPR002241	GO:0004553	hydrolase activity, hydrolyzing O-glycosyl compounds	MODIFY	yes	GO:0004557 alpha-galactosidase activity	The specific supported molecular function is alpha-galactosidase activity.
human	GLA	IPR000111,IPR002241	GO:0005975	carbohydrate metabolic process	MODIFY	yes	GO:0046479 glycosphingolipid catabolic process	Human GLA should be represented by the more specific lysosomal glycosphingolipid catabolic process.
human	GMFB	IPR002108	GO:0003779	actin binding	MODIFY	yes	GO:0071933 Arp2/3 complex binding	Falcon research explicitly notes that GMFB does not primarily bind actin directly and instead acts through Arp2/3.
human	GMFB	IPR011171	GO:0071846	actin filament debranching	ACCEPT	no		Actin filament debranching is a specific, supported biological process for GMFB.
human	GMFB	IPR011171	GO:0071933	Arp2/3 complex binding	ACCEPT	no		This is the most informative molecular-function term in the GMFB GOA file.
human	GMFG	IPR002108	GO:0003779	actin binding	MODIFY	yes	GO:0071933 Arp2/3 complex binding	Replace this generic term with the more informative Arp2/3 complex binding term, which is already present in GOA and better describes GMFG's core molecular function.
human	GMFG	IPR011171	GO:0071846	actin filament debranching	ACCEPT	no		Actin filament debranching is a specific, core biological process for GMFG and is supported by family/domain evidence.
human	GMFG	IPR011171	GO:0071933	Arp2/3 complex binding	ACCEPT	no		This is the most informative molecular-function annotation currently in GMFG GOA.
human	GNAS	IPR009434	GO:0071107	response to parathyroid hormone	MARK_AS_OVER_ANNOTATED	yes		PMID:22378814 shows that a deletion removing NESP55 affects imprinting and PHP1B, but this is a regulatory-locus effect. It should not be treated as a core biological process of the NESP55 protein product.
human	GOLGA8K	IPR024858,IPR043937	GO:0005794	Golgi apparatus	ACCEPT	no		The Golgi apparatus annotation is accurate based on the presence of GOLGA-family domains. While it is less specific than the IBA annotations for cis-Golgi localization, it is not incorrect. IEA annotations from InterPro mappings are generally reliable for cellular component when based on well-characterized domain families. The GOLGA domains have strong predictive value for Golgi localization.
human	GOLGA8K	IPR043937	GO:0005801	cis-Golgi network	ACCEPT	no		This annotation is a duplicate of the IBA annotation for the same GO term (GO:0005801) but with different evidence. Both IEA (from domain mapping) and IBA (from phylogeny) support cis-Golgi network localization. The redundancy is acceptable in GO as different evidence types can independently support the same annotation. The InterPro-based inference is consistent with the phylogenetic inference.
human	GPATCH11	IPR000467	GO:0003676	nucleic acid binding	ACCEPT	no		Domain-based IEA from G-patch (IPR000467); biologically consistent with the protein's spliceosomal role but not informative on its own.
human	GPC2	IPR001863	GO:0009966	regulation of signal transduction	ACCEPT	no		The annotation correctly captures the signaling co-receptor function of GPC2. This is a core function of all glypicans and is supported by specific interaction data for GPC2 with growth factors PTN and MDK.
human	GPC2	IPR001863	GO:0031012	extracellular matrix	KEEP_AS_NON_CORE	yes		Same rationale as IBA annotation - ECM is a secondary/non-core localization for this GPI-anchored cell surface proteoglycan.
human	GPC4	IPR001863	GO:0009966	regulation of signal transduction	ACCEPT	no		This accurately captures a core function of GPC4. The glypican family modulates signaling by binding ligands (Wnt, FGF, Hedgehog) through heparan sulfate chains and presenting them to receptors. GPC4 has experimentally demonstrated roles in Wnt signaling.
human	GPC4	IPR001863	GO:0031012	extracellular matrix	ACCEPT	no		Consistent with the IBA annotation for the same term. Glypicans with heparan sulfate chains interact with ECM components. This IEA provides additional support.
human	GPC6	IPR001863	GO:0009966	regulation of signal transduction	MODIFY	yes	GO:2000052 positive regulation of non-canonical Wnt signaling pathway; GO:0045880 positive regulation of smoothened signaling pathway	While regulation of signal transduction is accurate, more specific terms are available. GPC6 specifically activates non-canonical Wnt signaling and positively regulates Hedgehog/Smoothened signaling. Consider more specific annotations for these pathways.
human	GPC6	IPR001863	GO:0031012	extracellular matrix	MODIFY	yes	GO:0009986 cell surface	GPC6 is a GPI-anchored cell surface protein. While HSPGs can interact with ECM, GPC6 is membrane-anchored. The cell surface annotation (GO:0009986) is more accurate.
human	GPR101	IPR000276	GO:0004930	G protein-coupled receptor activity	ACCEPT	no		The UniProt record describes GPR101 as an orphan receptor and places it in the G-protein coupled receptor 1 family, and the IBA/InterPro evidence is consistent with the rhodopsin-like 7TM architecture.
human	GPR101	IPR000276	GO:0007186	G protein-coupled receptor signaling pathway	ACCEPT	no		The annotation is broad enough to reflect receptor-family inference without over-specifying ligand or downstream transducer.
human	GPR101	IPR000276,IPR017452	GO:0016020	membrane	KEEP_AS_NON_CORE	yes		Retain as a true broad cellular-component annotation; plasma membrane is the preferred core location.
human	GRPEL1	IPR000740	GO:0000774	adenyl-nucleotide exchange factor activity	ACCEPT	no		Correct IEA mapping. The GrpE domain (IPR000740) is a reliable predictor of adenyl-nucleotide exchange factor activity, and this is confirmed by both phylogenetic (IBA) and experimental evidence for GRPEL1.
human	GRPEL1	IPR000740,IPR009012	GO:0006457	protein folding	KEEP_AS_NON_CORE	yes		While GRPEL1 participates in the protein folding process through its NEF function in the HSPA9 chaperone cycle, protein folding is not its core evolved function. Its core function is nucleotide exchange factor activity (GO:0000774) within the mitochondrial protein import system. Protein folding is a downstream consequence of HSPA9 cycling that GRPEL1 facilitates, making it a non-core annotation.
human	GRPEL1	IPR000740	GO:0042803	protein homodimerization activity	ACCEPT	no		Homodimerization is a conserved property of GrpE family proteins, and there is experimental evidence that GRPEL1 can self-associate. However, note that in vivo the GRPEL1-GRPEL2 hetero-oligomer may be the predominant species.
human	GRPEL1	IPR000740	GO:0051087	protein-folding chaperone binding	ACCEPT	no		GRPEL1 is a co-chaperone that directly binds the protein-folding chaperone HSPA9 with high affinity. This binding is central to its nucleotide exchange factor function. Supported by multiple lines of evidence including co-IP, biolayer interferometry, and functional assays.
human	GTF2F2	IPR003196	GO:0005674	transcription factor TFIIF complex	ACCEPT	no		Correct complex membership for the TFIIF beta subunit (InterPro IPR003196 = TFIIF_beta); this duplicates the experimentally and phylogenetically supported GO:0005674 annotations and is at the right level of specificity.
human	GTF2F2	IPR003196	GO:0006366	transcription by RNA polymerase II	ACCEPT	no		This is a correct but broad parent process; it is consistent with the more specific initiation and elongation annotations and is supported by experimental IMP and TAS annotations to the same term.
human	GTPBP1	IPR000795,IPR004161	GO:0005525	GTP binding	ACCEPT	no		Well-supported molecular function underlying GTPase activity.
human	GTPBP2	IPR000795	GO:0003924	GTPase activity	KEEP_AS_NON_CORE	yes		Predicted GTPase activity is consistent with the GTPase fold, but experimentally GTPBP2's nucleotide handling is weak; retained as non-core rather than the defining function.
human	GTPBP2	IPR000795	GO:0005525	GTP binding	ACCEPT	no		GTP binding is directly observed (albeit weak) and is consistent with the GTPase fold.
human	GTPBP6	IPR006073,IPR016496,IPR030394	GO:0005525	GTP binding	ACCEPT	no		GTPBP6 is a GTPase with canonical G-domain motifs; GTP binding is a core molecular function that underlies its role as a maturation/recycling GTPase.
human	HADHB	IPR002155,IPR020610,IPR020613,IPR020615,IPR020616,IPR020617	GO:0016747	acyltransferase activity, transferring groups other than amino-acyl groups	KEEP_AS_NON_CORE	yes		Correct parent term based on thiolase domain (InterPro:IPR002155). More specific child terms should be used for core function.
human	APEX1	IPR005135	GO:0003824	catalytic activity	ACCEPT	no		This general term is correct but redundant given the more specific enzymatic activity annotations. It serves as a parent term for the specific catalytic activities of APEX1.
human	HBS1L	IPR000795	GO:0003924	GTPase activity	ACCEPT	no		Correct core molecular function; redundant with IBA/ISS annotations.
human	HBS1L	IPR000795,IPR004161	GO:0005525	GTP binding	ACCEPT	no		GTP binding is a well-supported molecular function underlying GTPase activity.
human	HCST	IPR009861	GO:0005102	signaling receptor binding	ACCEPT	no		HCST is a transmembrane adaptor whose receptor association is a core molecular feature.
human	HCST	IPR009861	GO:0043548	phosphatidylinositol 3-kinase binding	ACCEPT	no		PI3K binding through the phosphorylated YINM motif is central to HCST function.
human	HCST	IPR009861	GO:0050776	regulation of immune response	MODIFY	yes	GO:0042267 natural killer cell mediated cytotoxicity	HCST's best-supported immune process is DAP10-dependent activation of cytotoxic lymphocyte responses, including natural killer cell mediated cytotoxicity.
human	HCST	IPR009861	GO:0051897	positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction	ACCEPT	no		DAP10 recruits PI3K p85 and activates Akt downstream of receptor engagement.
human	HDAC4	IPR046949	GO:0000122	negative regulation of transcription by RNA polymerase II	ACCEPT	no		HDAC4 negatively regulates transcription of RNA polymerase II-transcribed genes by recruiting HDAC3/NCoR/SMRT corepressor complex to promoters. This is a well-established core function.
human	HDAC4	IPR046949	GO:0004407	histone deacetylase activity	ACCEPT	no		HDAC4 possesses a histone deacetylase catalytic domain and measurable deacetylase activity, even if weaker than class I HDACs. Duplicate of IBA annotation which is appropriate.
human	HES1	IPR003650	GO:0006355	regulation of DNA-templated transcription	ACCEPT	no		A correct high-level parent term consistent with HES1 function; more specific repressor terms are also present.
human	HES1	IPR011598,IPR036638	GO:0046983	protein dimerization activity	ACCEPT	no		The HLH domain mediates dimerization, a prerequisite for DNA binding; supported by the protein homodimerization annotations.
human	HINT2	IPR011146	GO:0003824	catalytic activity	MODIFY	yes	GO:0043530 adenosine 5'-monophosphoramidase activity	"Generic ""catalytic activity"" should be replaced with the specific enzymatic function GO:0043530 (adenosine 5'-monophosphoramidase activity) which is experimentally validated."
human	HPX	IPR016358	GO:0006879	intracellular iron ion homeostasis	ACCEPT	no		HPX-mediated heme scavenging is essential for iron conservation and recycling. The iron from HPX-delivered heme is recovered and redistributed for erythropoiesis.
human	HPX	IPR016358	GO:0015232	heme transmembrane transporter activity	REMOVE	yes		HPX is a soluble heme-binding plasma protein, not a transmembrane transporter. The actual transmembrane transport of heme occurs through other proteins like FLVCR1. HPX functions by binding heme extracellularly and being endocytosed with its cargo. This IEA annotation from InterPro mapping is erroneous.
human	HPX	IPR016358	GO:0015886	heme transport	ACCEPT	no		Heme transport is a core function of HPX. It scavenges free heme from plasma and transports it to hepatocytes and macrophages via LRP1-mediated endocytosis.
human	HRAS	IPR001806	GO:0003924	GTPase activity	ACCEPT	no		GTPase activity is the core catalytic molecular function of HRAS.
human	HRAS	IPR020849	GO:0007165	signal transduction	MODIFY	yes	GO:0007265 Ras protein signal transduction	HRAS is specifically a Ras-family signal-transduction GTPase, so the existing broad signal transduction term should be replaced with the specific Ras protein signal transduction term.
human	HRAS	IPR020849	GO:0016020	membrane	MODIFY	yes	GO:0005886 plasma membrane	HRAS lipidation targets it to specific membranes; the broad membrane term should be replaced with the more precise plasma membrane location that is central to its signaling.
human	HRC	IPR015666	GO:0005509	calcium ion binding	ACCEPT	no		Calcium ion binding is a core molecular function of HRC. The protein contains multiple histidine-rich acidic tandem repeats that bind calcium with high capacity (PMID:2037293, PMID:17526652). This annotation is correct.
human	HSCB	IPR004640	GO:0001671	ATPase activator activity	ACCEPT	no		"This is a core function of HSCB. The deep research indicates ""the J-protein cochaperone (HscB/Jac1/HSCB) dramatically increases stimulation (reported up to ~400-fold in bacterial systems)"" and ""HSCB binds ISCU and engages HSPA9 via its J-domain HPD motif to stimulate ATP hydrolysis"" (Maio & Rouault 2022). This ATPase activation is mechanistically central to Fe-S cluster transfer."
human	HSCB	IPR004640	GO:0044571	[2Fe-2S] cluster assembly	KEEP_AS_NON_CORE	yes		While HSCB is involved in Fe-S cluster biogenesis, it specifically functions in the transfer step rather than de novo assembly. The broader parent term GO:0016226 would be more accurate. Keeping as non-core acknowledges the relationship to Fe-S metabolism without implying direct assembly activity.
human	HSCB	IPR004640	GO:0051087	protein-folding chaperone binding	MODIFY	yes	GO:0030544 Hsp70 protein binding	"While HSCB does bind to a chaperone (HSPA9), the more specific term GO:0030544 'Hsp70 protein binding' would be more accurate since HSPA9 is specifically an Hsp70 family member. The interaction is well-documented: PMID:24606901 shows ""HSC20 physically interacts...and works together with its cognate chaperone, HSPA9."""
human	HSCB	IPR009073,IPR036386	GO:0051259	protein complex oligomerization	KEEP_AS_NON_CORE	yes		"HSCB dimerization has been noted in the literature. PMID:24606901 states ""The previously observed propensity of HSC20 to dimerize may allow two holo-ISCU molecules at neighboring binding sites to reorganize their adjacent [2Fe-2S] centers."" However, this is not a primary function but rather a structural property that facilitates its main Fe-S cluster delivery role."
human	HSPA13	IPR013126	GO:0005524	ATP binding	ACCEPT	no		Directly supported by the conserved HSP70 ATPase domain and documented ATPase activity.
human	HSPA13	IPR013126	GO:0016887	ATP hydrolysis activity	ACCEPT	no		Consistent with the documented peptide-independent ATPase activity of STCH.
human	HSPA14	IPR013126	GO:0005524	ATP binding	ACCEPT	no		Consistent with the HSP70 fold and the nucleotide-dependent chaperone cycle; ATP binding underlies the ATPase activity stimulated by DNAJC2.
human	HSPA14	IPR013126	GO:0016887	ATP hydrolysis activity	ACCEPT	no		Same enzymatic activity as the IBA annotation; supported by the HSP70 fold and by DNAJC2 stimulation of HSPA14 ATPase activity.
human	HSPA1L	IPR013126	GO:0016887	ATP hydrolysis activity	ACCEPT	no		ATP hydrolysis is a core molecular function of HSPA1L. This IEA annotation is correctly derived from InterPro domain mapping and is consistent with the IBA annotation and structural evidence.
human	HSPA2	IPR013126	GO:0016887	ATP hydrolysis activity	ACCEPT	no		ATP hydrolysis activity is the core catalytic function of HSPA2, confirmed by crystal structure of the ATPase domain (PDB:3I33). The IEA from InterPro is correct and consistent with the IBA annotation.
human	HSPA6	IPR013126	GO:0016887	ATP hydrolysis activity	ACCEPT	no		ATP hydrolysis activity is directly demonstrated for HSPA6 (PMID:21231916) and is correctly predicted from the HSP70 InterPro domain. The IEA is consistent with both IBA and IDA annotations for the same term.
human	HSPA8	IPR013126	GO:0016887	ATP hydrolysis activity	ACCEPT	no		Correct IEA annotation consistent with the IBA annotation for this core function.
human	HSPA9	IPR012725	GO:0006457	protein folding	ACCEPT	no		Correct process annotation consistent with the Hsp70 chaperone mechanism and the directly_involved_in process of the GO:0044183 core function.
human	HSPA9	IPR013126	GO:0016887	ATP hydrolysis activity	ACCEPT	no		Correct and appropriately specific; duplicate of the IBA/IDA ATP hydrolysis calls, all consistent with direct biochemical assays of human mortalin (PMID:18632665, PMID:25615450).
human	HSPA9	IPR012725	GO:0051082	unfolded protein binding	MODIFY	yes	GO:0044183 protein folding chaperone	HSPA9 should be represented as a protein folding chaperone rather than generic unfolded-protein binding. The existing HSPA9 annotation set already includes GO:0044183 and chaperone/refolding process terms, consistent with mtHsp70 biology.
human	HSPB2	IPR003090	GO:0005212	structural constituent of eye lens	REMOVE	yes		HSPB2 is not a lens crystallin and is expressly absent from the lens; the term is incorrectly transferred from the broader alpha-crystallin/sHSP family.
human	HSPB6	IPR003090	GO:0005212	structural constituent of eye lens	REMOVE	yes		HSPB6 is not a structural constituent of the eye lens. It shares the alpha-crystallin domain with lens crystallins but is expressed in muscle tissues, not the lens. This annotation results from an overly broad InterPro domain-to-GO term mapping. The alpha-crystallin domain confers chaperone activity across the sHSP family, but the lens structural function is specific to CRYAA and CRYAB.
human	HSPB7	IPR037885	GO:0007507	heart development	KEEP_AS_NON_CORE	yes		Plausible given the strong cardiac/cardiovascular expression of cvHsp, but derived from an InterPro-to-GO family rule rather than direct experimental evidence for this gene; retained as a non-core process.
human	HSPB8	IPR043254	GO:0034620	cellular response to unfolded protein	ACCEPT	no		Redundant with the IBA and IMP annotations of the same process, all supported by HSPB8's documented anti-aggregation chaperone activity.
human	HSPB8	IPR043254	GO:0042803	protein homodimerization activity	ACCEPT	no		Recombinant HSPB8 forms stable dimers by size-exclusion and crosslinking, corroborating this electronic annotation.
human	HSPG2	IPR001881	GO:0005509	calcium ion binding	MARK_AS_OVER_ANNOTATED	yes		While perlecan contains EGF-like domains that structurally may bind calcium, this is not a characterized molecular function of perlecan and does not contribute to its known biological activities. This represents computational over-annotation based on domain presence without functional validation.
human	ICA1	IPR010504	GO:0019904	protein domain specific binding	ACCEPT	no		"Accurate automated annotation. The InterPro mapping correctly identifies that ICA1's arfaptin homology (AH) domain mediates protein domain-specific binding. ICA1 forms heterodimers with PICK1 through BAR domain interactions and binds Rab2 GTPases. While ""protein domain specific binding"" is more informative than generic ""protein binding"", it could still be more specific."
human	ICA1L	IPR010504	GO:0019904	protein domain specific binding	ACCEPT	no		"Accurate molecular function term that describes ICA1L's protein-protein interaction mechanism. The arfaptin/BAR domain of ICA1L recognizes and binds to the BAR-like domain of PICK1, forming heterodimers analogous to the well-characterized ICA69-PICK1 interaction. This is a clear example of protein domain-specific binding where the BAR domain serves as both the binding module and the binding target. The term is more informative than generic ""protein binding"" (GO:0005515) as it specifies the mechanism involves domain recognition. This function is critical for ICA1L's role in forming scaffolding complexes at vesicle membranes."
human	IDH3B	IPR019818	GO:0000287	magnesium ion binding	MARK_AS_OVER_ANNOTATED	yes		While the InterPro domain is present, the functional magnesium/metal binding site is located in the catalytic alpha subunit. IDH3B shares sequence/structural homology with dehydrogenases but its specific role is structural, not catalytic. This IEA annotation represents domain-based inference that does not reflect the actual function of this specific subunit.
human	IDH3B	IPR019818	GO:0016616	oxidoreductase activity, acting on the CH-OH group of donors, NAD or NADP as acceptor	REMOVE	yes		IDH3B does not have intrinsic oxidoreductase activity. The beta subunit alone shows no detectable enzymatic activity [PMID:10601238]. This annotation incorrectly attributes the catalytic activity of the complex to the non-catalytic beta subunit based solely on domain homology.
human	IDH3B	IPR019818	GO:0051287	NAD binding	MARK_AS_OVER_ANNOTATED	yes		The annotation is based on domain homology rather than demonstrated function. IDH3B contributes to the complex structure and ADP-mediated regulation but is not itself the primary NAD-binding subunit. The catalytic NAD binding site is in IDH3A. Crystal structures of the alphabeta heterodimer (PDB 6KDY NAD-bound, 6KE3 NADH-bound) show that the NAD cofactor binds in the active-site cleft built jointly from the alpha subunit and the small domain of the beta subunit, so the beta subunit contributes to the architecture of the holoenzyme NAD-binding/active site rather than binding NAD as an isolated subunit [PMID:31515270].
human	IFI16	IPR040205	GO:0002218	activation of innate immune response	ACCEPT	no		This IEA annotation is consistent with the IBA annotation and extensive experimental evidence supporting IFI16's role in innate immune activation.
human	IFI16	IPR040205	GO:0035458	cellular response to interferon-beta	ACCEPT	no		This annotation is consistent with IFI16's role as an interferon-inducible gene that mediates interferon-stimulated responses.
human	IFI30	IPR004911	GO:0016671	oxidoreductase activity, acting on a sulfur group of donors, disulfide as acceptor	ACCEPT	no		GO:0016671 is a child of GO:0016667 and specifies that the acceptor is a disulfide bond, which is precisely what GILT does. This is the most specific MF term applicable to GILT's catalytic activity. The InterPro domain (IPR004911 - Interferon-induced_GILT) correctly predicts this function. PMID:10639150 demonstrated experimentally that GILT reduces disulfide bonds in protein substrates.
human	IFNL4	IPR029177	GO:0007259	cell surface receptor signaling pathway via JAK-STAT	ACCEPT	no		cell surface receptor signaling pathway via JAK-STAT is supported as part of the core type III interferon cytokine function of IFNL4.
human	IFNL4	IPR029177	GO:0050778	positive regulation of immune response	ACCEPT	no		positive regulation of immune response is supported as part of the core type III interferon cytokine function of IFNL4.
human	IL13	IPR001325,IPR018096	GO:0005126	cytokine receptor binding	ACCEPT	no		This is a correct parent term of GO:0005144 (interleukin-13 receptor binding). While more general than the IBA annotation, it is not incorrect as an IEA. The more specific term is captured by IBA evidence.
human	IL13	IPR001325,IPR018096	GO:0006955	immune response	ACCEPT	no		Correct broad annotation. IL-13 is fundamentally an immune cytokine. The term is general but not incorrect for an IEA.
human	IL15	IPR003443	GO:0005126	cytokine receptor binding	ACCEPT	no		ACCEPT: IL15 binds cytokine receptors. UniProt INTERACTION section shows IL15 binds IL15RA and IL2RB. This is core to its function.
human	IL15	IPR003443	GO:0006955	immune response	ACCEPT	no		"ACCEPT: IL15 functions in immune response. UniProt: ""plays a major role in the development of inflammatory and protective immune responses."""
human	IL21	IPR003443	GO:0006955	immune response	MARK_AS_OVER_ANNOTATED	yes		Very general term. All cytokine activity involves immune response. More specific terms are appropriate for IL21 function.
human	IL36RN	IPR003297	GO:0005149	interleukin-1 receptor binding	ACCEPT	no		Accurate - IL-36R is IL-1Rrp2, an IL-1 receptor family member.
human	IL36RN	IPR000975	GO:0006954	inflammatory response	ACCEPT	no		Core process - duplicate of IBA annotation.
human	IL36RN	IPR000975	GO:0006955	immune response	ACCEPT	no		Core process - duplicate of IBA annotation.
human	IL4	IPR001325,IPR018096	GO:0005126	cytokine receptor binding	ACCEPT	no		This is a correct but less specific parent term. Since the more specific GO:0005136 is also annotated, this IEA annotation is redundant but not incorrect. Acceptable as an IEA capturing the broader category.
human	IL4	IPR002354	GO:0005136	interleukin-4 receptor binding	ACCEPT	no		This is the core molecular function of IL-4 as a ligand. The IEA annotation from InterPro domain mapping is correct and supported by extensive structural and biochemical data, including crystal structures of the IL-4/IL4RA complex.
human	IL4	IPR001325,IPR002354,IPR018096	GO:0006955	immune response	ACCEPT	no		This is a very general but correct IEA annotation. IL-4 is fundamentally an immune response mediator. More specific terms are also annotated. Acceptable as a broad IEA classification.
human	IL7R	IPR003531	GO:0004896	cytokine receptor activity	ACCEPT	no		Cytokine receptor activity is a correct parent-level annotation. IL7R belongs to the type I cytokine receptor family and functions as a receptor for both IL-7 and TSLP cytokines. The IEA annotation is appropriately general given the domain-based evidence.
human	IL7R	IPR003531	GO:0016020	membrane	ACCEPT	no		While very general and redundant with plasma membrane, this IEA annotation from InterPro is technically correct. IL7R is an integral membrane protein.
human	ILF3	IPR033099	GO:0003725	double-stranded RNA binding	ACCEPT	no		ILF3 has tandem dsRNA-binding domains with structural evidence for sequence/structure-sensitive dsRNA recognition.
human	ILK	IPR001245	GO:0004672	protein kinase activity	REMOVE	yes		Electronic over-propagation refuted on biological grounds: ILK is established as a catalytically dead scaffold (the curated NOT|ser/thr kinase). Remove.
human	ILK	IPR000719	GO:0005524	ATP binding	KEEP_AS_NON_CORE	yes		Real (structurally demonstrated) nucleotide binding but not catalytic; non-core for a scaffold.
human	INTU	IPR039151	GO:0001736	establishment of planar polarity	ACCEPT	no		PMID:26644512 demonstrated that INTU is essential for establishing planar cell polarity by linking NPHP4 to DAAM1 to control the subapical actin network required for proper ciliary orientation in multiciliated cells.
human	INTU	IPR043987,IPR043988,IPR043989	GO:0016192	vesicle-mediated transport	REMOVE	yes		No evidence supports a direct role in vesicle-mediated transport. This appears to be an incorrect automated annotation, possibly based on superficial similarity to IFT proteins. INTU functions in intraciliary transport, not vesicle transport.
human	IP6K3	IPR005522	GO:0032958	inositol phosphate biosynthetic process	ACCEPT	no		This biological-process term matches the characterized IP6K3 reaction products and Reactome inositol phosphate pathway context.
human	IRF4	IPR001346	GO:0000976	transcription cis-regulatory region binding	ACCEPT	no		This IEA annotation is accurate but less specific than the IBA annotation for GO:0000978. The InterPro-based mapping correctly identifies cis-regulatory region binding as a function of the IRF DNA-binding domain. It is acceptable as a broader parent of the more specific IBA terms.
human	IRF4	IPR019471,IPR019817	GO:0006355	regulation of DNA-templated transcription	ACCEPT	no		This is a correct but general annotation. IRF4 is a transcription factor and regulation of DNA-templated transcription is its core biological process. While more specific terms exist (e.g., GO:0006357 regulation of transcription by RNA polymerase II), this broader IEA annotation from InterPro mapping is not wrong.
human	IRF8	IPR001346	GO:0000976	transcription cis-regulatory region binding	ACCEPT	no		This is a parent term of the more specific GO:0000978 (RNA polymerase II cis-regulatory region sequence-specific DNA binding). The IEA annotation is consistent with IRF8's known DNA-binding function and supported by IBA annotation to the child term.
human	IRF8	IPR019471,IPR019817	GO:0006355	regulation of DNA-templated transcription	ACCEPT	no		This is a parent term of GO:0006357 (regulation of transcription by RNA polymerase II). Consistent with IRF8's core function as a transcription factor.
human	ISCA1	IPR016092	GO:0016226	iron-sulfur cluster assembly	MODIFY	yes	GO:0044572 [4Fe-4S] cluster assembly	While correct at the general level, ISCA1 specifically functions in [4Fe-4S] cluster assembly, not in [2Fe-2S] assembly. The more specific term GO:0044572 ([4Fe-4S] cluster assembly) would be more accurate.
human	ISCA2	IPR016092	GO:0016226	iron-sulfur cluster assembly	ACCEPT	no		This IEA annotation is correct based on domain analysis (FeS_cluster_insertion domain IPR016092). Consistent with ISCA2's role in Fe-S biogenesis and the IBA annotation for the same term.
human	ISCU	IPR002871,IPR011339	GO:0005506	iron ion binding	ACCEPT	no		The IEA is correct based on domain analysis. It is more general than the IBA annotation for ferrous iron binding, but both can coexist as the IEA provides independent computational evidence.
human	ISCU	IPR002871,IPR011339	GO:0016226	iron-sulfur cluster assembly	ACCEPT	no		Iron-sulfur cluster assembly is the primary biological process for ISCU. This is appropriate as the parent term for more specific [2Fe-2S] cluster assembly.
human	ISCU	IPR002871,IPR011339	GO:0051536	iron-sulfur cluster binding	ACCEPT	no		General term for Fe-S cluster binding is appropriate as it encompasses the more specific [2Fe-2S] cluster binding function. Domain analysis supports this annotation.
human	ITIH2	IPR010600	GO:0030212	hyaluronan metabolic process	ACCEPT	no		"This annotation accurately captures a core function of ITIH2. The protein is directly involved in hyaluronan metabolic processes through its interactions with hyaluronan. PMID:20463016 demonstrates that ""TSG-6/HC2 transfer HCs from bikunin proteins to HA"" and shows ""a dynamic shuffling of the HCs occur in vivo"" between glycosaminoglycans including hyaluronan. The deep research confirms ITIH2 ""binds and stabilizes hyaluronan in the ECM"" and is ""covalently linking to hyaluronan, mediated by TSG-6."" UniProt states ITIH2 may act as ""a binding protein between hyaluronan and other matrix protein...to regulate the localization, synthesis and degradation of hyaluronan."""
human	JAK1	IPR000719,IPR001245,IPR008266	GO:0004672	protein kinase activity	KEEP_AS_NON_CORE	yes		Accurate but GO:0004715 (non-membrane spanning protein tyrosine kinase activity) is more specific and preferred.
human	JAK1	IPR016251,IPR020776	GO:0035556	intracellular signal transduction	KEEP_AS_NON_CORE	yes		While accurate, this is too general. More specific terms like JAK-STAT pathway and cytokine signaling better describe JAK1's core function.
human	JAK1	IPR016251,IPR020776	GO:0016020	membrane	MARK_AS_OVER_ANNOTATED	yes		Membrane is an overly broad localization; JAK1 is a cytosolic kinase that associates with the cytoplasmic side of the plasma membrane via receptor binding. More specific terms (cytosol, extrinsic component of cytoplasmic side of plasma membrane) are preferred.
human	KCNRG	IPR003131	GO:0051260	protein homooligomerization	ACCEPT	no		The T1/BTB domain in KCNRG is structurally related to the tetramerization domains of Kv channels. Homooligomerization is consistent with the domain architecture and is experimentally supported.
human	KCTD11	IPR003131	GO:0051260	protein homooligomerization	ACCEPT	no		PMID:27152988 demonstrated by electron microscopy that KCTD BTB domains form pentamers. PMID:21237243 shows the protein forms oligomers. This is a well-established structural property essential for CRL3 function.
human	KCTD12	IPR003131	GO:0051260	protein homooligomerization	ACCEPT	no		The InterPro-based annotation correctly infers homo-oligomerization from the BTB domain. Experimental evidence confirms KCTD12 forms tetrameric/pentameric assemblies. This self-association is characteristic of KCTD family proteins and essential for GABA-B receptor auxiliary subunit function.
human	KCTD14	IPR003131	GO:0051260	protein homooligomerization	ACCEPT	no		The annotation is well-supported by structural homology. The BTB/POZ domain is a well-characterized oligomerization domain. Family-wide AlphaFold analyses confirm that KCTD proteins typically form pentameric assemblies via their BTB domains. While direct experimental evidence for KCTD14 oligomerization is lacking, the structural prediction is robust given the high conservation of oligomerization function across BTB domains.
human	KCTD16	IPR003131	GO:0051260	protein homooligomerization	ACCEPT	no		This annotation is strongly supported by structural evidence. Crystal structures show KCTD16 forms an open pentamer via its BTB/T1 domain (Zuo et al. 2019, Pinkas et al. 2017). The pentamerization is functionally important for receptor complex assembly.
human	KCTD18	IPR003131	GO:0051260	protein homooligomerization	REMOVE	yes		Recent AlphaFold2-based structural analysis predicts KCTD18 is monomeric rather than oligomeric [Balasco et al., 2024]. While the T1-type BTB domain in many proteins does mediate oligomerization, KCTD18 appears to be an outlier in the KCTD family. The InterPro-based inference is too broad and does not account for protein-specific structural features. This annotation should be removed until experimental evidence (e.g., SEC-MALS, native MS) confirms the oligomeric state.
human	KCTD4	IPR003131	GO:0051260	protein homooligomerization	ACCEPT	no		The protein homooligomerization annotation is supported by structural predictions and family-level evidence. AlphaFold-based analysis specifically assigns KCTD4 to a pentameric assembly cluster (Balasco et al. 2024). The InterPro2GO mapping is appropriate given the T1-type BTB domain (IPR003131) present in KCTD4, which is known to mediate oligomerization.
human	KCTD7	IPR003131	GO:0051260	protein homooligomerization	ACCEPT	no		Well-supported by domain architecture. The BTB/POZ domain (IPR000210) mediates oligomerization. Structural work shows KCTD family proteins form homopentamers. The deep research states structural work across KCTDs shows homopentameric BTB assemblies (KCTD7-deep-research-falcon.md).
human	KCTD8	IPR003131	GO:0051260	protein homooligomerization	ACCEPT	no		Pentamer formation is the functional oligomeric state for KCTD8 as demonstrated by structural studies of the KCTD family. The BTB-mediated pentamerization is required for receptor scaffolding and signaling modulation.
human	KIF5B	IPR001752,IPR019821	GO:0005524	ATP binding	MODIFY	yes	GO:0008574 plus-end-directed microtubule motor activity	Use the specific plus-end-directed microtubule motor activity rather than separate generic ATP-binding or microtubule-binding terms as the reviewed molecular function.
human	KIF5B	IPR001752,IPR019821,IPR027640	GO:0007018	microtubule-based movement	MODIFY	yes	GO:0047496 vesicle transport along microtubule	Replace the broad process with the cargo-transport process already supported in GOA.
human	KIF5B	IPR001752	GO:0008017	microtubule binding	MODIFY	yes	GO:0008574 plus-end-directed microtubule motor activity	Use the specific plus-end-directed microtubule motor activity rather than separate generic ATP-binding or microtubule-binding terms as the reviewed molecular function.
human	KRAS	IPR001806	GO:0003924	GTPase activity	ACCEPT	no		This is the core molecular activity of KRAS. The UniProt record, Reactome intrinsic GTPase reaction, and biochemical KRAS mutant studies all support GTP hydrolysis as the central catalytic activity.
human	KRAS	IPR001806,IPR005225,IPR020849	GO:0005525	GTP binding	ACCEPT	no		GTP binding is essential to KRAS activation and downstream effector recruitment.
human	KRAS	IPR020849	GO:0007165	signal transduction	MODIFY	yes	GO:0007265 Ras protein signal transduction	KRAS should be annotated to Ras protein signal transduction rather than broad signal transduction when the domain and pathway evidence are Ras-specific.
human	KRAS	IPR020849	GO:0016020	membrane	MARK_AS_OVER_ANNOTATED	yes		KRAS has more specific and better-supported plasma membrane, cytoplasmic-side-of-plasma-membrane, endomembrane, and cytosolic localization annotations. Generic membrane should not be used as an informative KRAS localization.
human	LAMP1	IPR002000	GO:0016020	membrane	MODIFY	yes	GO:0005765 lysosomal membrane	Replace the broad membrane/vesicle term with lysosomal membrane, the informative core location.
human	LIPE	IPR010468	GO:0016298	lipase activity	MODIFY	yes	GO:0120516 diacylglycerol lipase activity	lipase activity is less informative than the reviewed LIPE/HSL lipolysis term.
human	LMAN1	IPR005052	GO:0016020	membrane	MARK_AS_OVER_ANNOTATED	yes		Uninformative generic term; the specific compartment-membrane annotations are preferable. ER/ERGIC membrane would be the appropriate refinement.
human	LMAN1L	IPR005052	GO:0016020	membrane	MARK_AS_OVER_ANNOTATED	yes		Uninformative generic parent; the specific ERGIC membrane term captures the localization better.
human	LMAN2	IPR005052	GO:0016020	membrane	MARK_AS_OVER_ANNOTATED	yes		Uninformative parent term; the specific early-secretory-pathway membrane compartments (GO:0005789, GO:0033116, GO:0000139) capture the localization more precisely.
human	LMAN2L	IPR005052	GO:0016020	membrane	MARK_AS_OVER_ANNOTATED	yes	GO:0005789 endoplasmic reticulum membrane	Uninformative high-level compartment; the specific ER membrane (GO:0005789) term is the appropriate localization.
human	LONP2	IPR027065	GO:0030163	protein catabolic process	ACCEPT	no		Accurate. LONP2 mediates protein degradation/catabolism in the peroxisomal matrix. This is a general term that correctly describes LONP2's proteolytic degradation function.
human	LPCAT1	IPR045252	GO:0008374	O-acyltransferase activity	MARK_AS_OVER_ANNOTATED	yes		This is a parent term of the specific O-acyltransferase activities annotated. The child terms provide much more informative functional annotation.
human	LPCAT1	IPR002048	GO:0005509	calcium ion binding	ACCEPT	no		The EF-hand domains are structurally validated and calcium modulation of activity has been demonstrated. However, it's notable that UniProt states the acyltransferase activity itself is calcium-independent (by similarity), suggesting the EF-hands may have a regulatory rather than catalytic role.
human	LPCAT2	IPR002048	GO:0005509	calcium ion binding	ACCEPT	no		Calcium binding via EF-hand domains is structurally predicted and functionally relevant - LPCAT2's activity is Ca2+-dependent.
human	LPCAT2	IPR045252	GO:0008374	O-acyltransferase activity	MARK_AS_OVER_ANNOTATED	yes		This is a parent term of the more specific acyltransferase activities that LPCAT2 possesses. The specific activities are more informative.
human	LRCOL1	IPR001981	GO:0005576	extracellular region	ACCEPT	no		Well-supported secreted protein. Confirmed experimentally and by domain analysis.
human	LRCOL1	IPR001981	GO:0007586	digestion	ACCEPT	no		Supported by expression in digestive tissues and structural homology to pancreatic colipase which is central to fat digestion.
human	LRCOL1	IPR001981	GO:0008047	enzyme activator activity	ACCEPT	no		Core molecular function inferred from colipase-like domains and expression pattern. Colipase proteins are canonical enzyme activators.
human	LRCOL1	IPR001981	GO:0016042	lipid catabolic process	ACCEPT	no		Consistent with enzyme activator function and expression in lipid-metabolic tissues.
human	LTN1	IPR011016	GO:0008270	zinc ion binding	KEEP_AS_NON_CORE	yes		Accurate structural feature of the RING domain (residues 1715-1762) but subsidiary to the informative ubiquitin ligase activity; not a standalone core function.
human	LTN1	IPR039795	GO:1990112	RQC complex	ACCEPT	no		Correct; LTN1 is a defining RQC complex subunit.
human	LTN1	IPR039795	GO:1990116	ribosome-associated ubiquitin-dependent protein catabolic process	ACCEPT	no		Correct defining biological process; redundant with IDA/IBA.
human	LYRM4	IPR045297	GO:0016226	iron-sulfur cluster assembly	ACCEPT	no		The annotation is correct and well-supported by domain analysis and experimental evidence.
human	CNKSR3	IPR010599	GO:0009966	regulation of signal transduction	ACCEPT	no		Accurate representation of CNKSR3's biological role as a regulator of signaling pathways. The protein negatively regulates ERK1/2 cascade and peptidyl-serine phosphorylation while positively regulating ENaC-mediated sodium transport.
human	CNKSR3	IPR010599	GO:0016020	membrane	MODIFY	yes	GO:0016324 apical plasma membrane	The term 'membrane' is too general. CNKSR3 specifically localizes to the apical plasma membrane where it functions in ENaC regulation. A more specific term is warranted.
human	MAML1	IPR046369	GO:0007221	positive regulation of transcription of Notch receptor target	ACCEPT	no		This term is more specific than broad Notch signaling pathway and is directly supported by HES1 activation evidence.
human	MAN1B1	IPR001382,IPR036026	GO:0005509	calcium ion binding	KEEP_AS_NON_CORE	yes		Accurate structural cofactor requirement of the GH47 fold but not a standalone core function; the catalytic mannosidase activity is the informative function.
human	MAN1B1	IPR012341	GO:0005975	carbohydrate metabolic process	MARK_AS_OVER_ANNOTATED	yes		Over-general; the specific ER mannose trimming (GO:1904380) and ER N-glycan trimming (GO:0140277) terms better capture the biology.
human	MAN1B1	IPR001382,IPR036026	GO:0016020	membrane	MARK_AS_OVER_ANNOTATED	yes	GO:0005789 endoplasmic reticulum membrane	Uninformative parent; MAN1B1 is specifically an ER membrane protein.
human	MAP1S	IPR026074	GO:0000226	microtubule cytoskeleton organization	ACCEPT	no		Core biological process; consistent with experimental microtubule bundling/organization evidence.
human	MAP1S	IPR026074	GO:0005874	microtubule	ACCEPT	no		Core localization; MAP1S associates with microtubules.
human	MAP3K20	IPR000719,IPR001245,IPR008271	GO:0004672	protein kinase activity	ACCEPT	no		Correct but general; the specific MF terms (protein serine/threonine kinase, MAP kinase kinase kinase) are more informative and also annotated.
human	MAP3K5	IPR043969	GO:0000165	MAPK cascade	ACCEPT	no		While correct and acceptable as a broader parent term, the more specific JNK cascade and p38MAPK cascade annotations capture the actual function better. This IEA annotation provides appropriate general coverage.
human	MAP3K5	IPR000719,IPR008271	GO:0004672	protein kinase activity	MARK_AS_OVER_ANNOTATED	yes		Protein kinase activity is technically correct but redundant with the more specific MAP kinase kinase kinase activity. The more specific term should be preferred.
human	MAP7	IPR008604	GO:0000226	microtubule cytoskeleton organization	ACCEPT	no		Correct annotation consistent with MAP7's core function in microtubule stabilization and organization. Redundancy with IBA is acceptable.
human	MAP7	IPR008604	GO:0015630	microtubule cytoskeleton	ACCEPT	no		Correct annotation, though redundant with higher-quality evidence annotations.
human	MAP7D1	IPR008604	GO:0000226	microtubule cytoskeleton organization	ACCEPT	no		The InterPro-based inference is accurate. The MAP7 domain (IPR008604) is indeed associated with microtubule binding and organization. This is redundant with the IBA annotation but is an independent line of evidence supporting the same function.
human	MAP7D1	IPR008604	GO:0015630	microtubule cytoskeleton	ACCEPT	no		This IEA annotation correctly captures microtubule cytoskeleton localization based on the MAP7 domain. Redundant with the IBA but provides independent computational support.
human	MAP7D3	IPR008604	GO:0000226	microtubule cytoskeleton organization	ACCEPT	no		While this is an automated annotation based on domain presence, it is consistent with experimental evidence and the IBA annotation. The MAP7 domain (IPR008604) is characteristic of proteins involved in microtubule cytoskeleton organization.
human	MAP7D3	IPR008604	GO:0015630	microtubule cytoskeleton	ACCEPT	no		The automated annotation based on MAP7 family domain presence is consistent with experimental evidence showing MAP7D3 localizes to microtubules. This annotation is appropriately redundant with the IBA annotation.
human	MAPK1	IPR000719,IPR003527,IPR008349,IPR017441	GO:0005524	ATP binding	ACCEPT	no		ATP binding is integral to the active-site chemistry of ERK2 kinase activity.
human	MCTS1	IPR002478,IPR004521	GO:0003723	RNA binding	KEEP_AS_NON_CORE	yes		Correct but generic; the specific informative activities are 40S binding, cap-complex/PUA-mediated mRNA engagement and reinitiation-factor activity.
human	MED13L	IPR009401	GO:0003712	transcription coregulator activity	ACCEPT	no		This is a core molecular function of MED13L. The protein is part of the Mediator complex and directly regulates transcription as a coregulator. PMID:22249253 demonstrates that MED13L is required for Rb/E2F transcriptional control. Deep research provides structural basis for the coregulatory mechanism.
human	MED13L	IPR009401	GO:0006357	regulation of transcription by RNA polymerase II	ACCEPT	no		This is the core biological process function of MED13L. The protein regulates Pol II transcription by controlling access of Pol II to the core Mediator through its intrinsically disordered regions.
human	MED13L	IPR009401	GO:0016592	mediator complex	ACCEPT	no		This is a valid cellular component annotation for MED13L. The gene encodes Mediator of RNA polymerase II transcription subunit 13-like, and MED13L is a bona fide subunit of the Mediator complex. Deep research confirms MED13L as a CKM tether that links the CKM to core Mediator. While a more specific annotation to CKM complex (GO:1990508) could be added, this general annotation remains correct.
human	MEFV	IPR000315	GO:0008270	zinc ion binding	KEEP_AS_NON_CORE	yes		Pyrin contains a B-box zinc finger that binds zinc structurally; correct but a structural/accessory property rather than the core inflammasome-sensing function.
human	MEX3B	IPR004087	GO:0003676	nucleic acid binding	MODIFY	yes	GO:0003730 mRNA 3'-UTR binding	MEX3B is specifically an RNA-binding protein, not a general nucleic acid binder. The more specific term GO:0003723 (RNA binding) or even GO:0003730 (mRNA 3'-UTR binding) better captures its function.
human	MGP	IPR000294,IPR035972	GO:0005509	calcium ion binding	ACCEPT	no		Calcium ion binding through Gla residues is the fundamental molecular function that enables MGP's biological activity. The Gla domain contains five glutamic acid residues that undergo vitamin K-dependent gamma-carboxylation, creating high-affinity calcium binding sites. This is supported by structural and functional studies showing calcium binding induces conformational changes necessary for MGP function.
human	MGP	IPR002384	GO:0030500	regulation of bone mineralization	MODIFY	yes	GO:0140928 inhibition of non-skeletal tissue mineralization	"While MGP does regulate mineralization processes, the current term focuses on ""bone mineralization"" which does not capture MGP's primary function of preventing ectopic calcification in soft tissues. MGP's most critical role is as an inhibitor of vascular calcification and inappropriate cartilage calcification. The more specific term GO:0140928 ""inhibition of non-skeletal tissue mineralization"" precisely describes this function."
human	MGP	IPR027118	GO:0031012	extracellular matrix	ACCEPT	no		Duplicate of the IBA annotation already reviewed. The IEA evidence is from InterPro domain IPR027118 (MGP family domain), which confirms the localization. Duplicates with different evidence codes are acceptable in GO annotation.
human	MKKS	IPR002423	GO:0005524	ATP binding	KEEP_AS_NON_CORE	yes		Sequence/domain-based inference consistent with the chaperonin fold; retain as a plausible non-core molecular attribute pending experimental confirmation.
human	MKKS	IPR028790	GO:0006457	protein folding	KEEP_AS_NON_CORE	yes		Domain-based inference; plausible but the experimentally supported activity is chaperone-mediated complex assembly rather than general protein folding.
human	MKRN1	IPR045072	GO:0000209	protein polyubiquitination	ACCEPT	no		MKRN1 mediates proteasome-dependent degradation of p53/p21 via polyubiquitination.
human	MKRN1	IPR000571,IPR018957,IPR036855	GO:0046872	metal ion binding	KEEP_AS_NON_CORE	yes		Zinc coordination by the RING and zinc-finger motifs is structurally required, but the informative functions are E3 ligase activity and RNA binding.
human	MKRN2	IPR045072	GO:0000209	protein polyubiquitination	ACCEPT	no		Consistent with E3 ligase activity and reported RELA degradation.
human	MKRN2	IPR000571,IPR036855	GO:0046872	metal ion binding	KEEP_AS_NON_CORE	yes		Zinc coordination is structurally required; the informative functions are E3 ligase activity and RNA binding.
human	MLEC	IPR039155	GO:0030246	carbohydrate binding	ACCEPT	no		This general term is appropriate as malectin has demonstrated carbohydrate binding activity. Malectin binds specifically to Glc2Man9GlcNAc2 (G2M9) N-glycans with Ka approximately 1.97 x 10^5 M^-1, recognizing the Glc-alpha-1,3-Glc (nigerose) disaccharide epitope.
human	MMS19	IPR039920	GO:0051604	protein maturation	ACCEPT	no		This IEA annotation from InterPro correctly identifies the protein maturation function of MMS19. While duplicative with other annotations, it provides additional computational evidence supporting the experimentally validated function.
human	MORC3	IPR045261	GO:0016887	ATP hydrolysis activity	ACCEPT	no		ATP hydrolysis activity is a core molecular feature of MORC3.
human	MTX1	IPR019564	GO:0001401	SAM complex	ACCEPT	no		Correct InterPro-derived complex annotation. The Falcon review identifies MTX1 as a mammalian SAM complex accessory subunit.
human	MTX2	IPR019564	GO:0001401	SAM complex	ACCEPT	no		Correct InterPro-derived annotation. The Falcon synthesis supports MTX2 as a SAM/metaxin factor at the mitochondrial outer membrane.
human	MVB12A	IPR040335	GO:0000813	ESCRT I complex	ACCEPT	no		MVB12A is a metazoan fourth subunit of ESCRT-I and is directly supported by ESCRT-I composition and structural studies.
human	MYC	IPR002418,IPR003327,IPR012682	GO:0003700	DNA-binding transcription factor activity	ACCEPT	no		This IEA annotation from InterPro correctly identifies MYC as a DNA-binding transcription factor based on its bHLH-LZ domain structure.
human	MYC	IPR011598,IPR036638	GO:0046983	protein dimerization activity	ACCEPT	no		Protein dimerization (specifically heterodimerization with MAX) is a core molecular function of MYC that is essential for DNA binding and transcriptional activity. The IEA annotation correctly identifies this function from InterPro domains.
human	NAA10	IPR000182	GO:0016747	acyltransferase activity, transferring groups other than amino-acyl groups	MARK_AS_OVER_ANNOTATED	yes		This high-level acyltransferase term adds no information beyond the specific Nt-acetyltransferase activity; uninformative.
human	NAA30	IPR044542	GO:0004596	protein-N-terminal amino-acid acetyltransferase activity	ACCEPT	no		NAA30 is the catalytic subunit of NatC; this MF is its core function and is corroborated by direct experimental (IDA) evidence.
human	NAA30	IPR000182	GO:0016747	acyltransferase activity, transferring groups other than amino-acyl groups	MARK_AS_OVER_ANNOTATED	yes		This is a broad GNAT-fold parent term less precise than the specific N-terminal acetyltransferase activity that is experimentally established for NAA30; the specific terms (GO:0004596 / GO:0120518) already capture the function.
human	NAA35	IPR007244	GO:0031417	NatC complex	ACCEPT	no		Correct and well-corroborated NatC complex membership.
human	NAA38	IPR047575	GO:0003723	RNA binding	MARK_AS_OVER_ANNOTATED	yes		RNA binding is inferred purely from the Sm-like domain signature and does not reflect a demonstrated function of NAA38 within NatC; the experimentally supported role is as a non-catalytic NatC subunit.
human	NAA40	IPR039949	GO:0010485	histone H4 acetyltransferase activity	ACCEPT	no		Core activity; redundant with IDA/IBA H4 annotations.
human	NAA40	IPR000182	GO:0016747	acyltransferase activity, transferring groups other than amino-acyl groups	MARK_AS_OVER_ANNOTATED	yes		High-level acyltransferase term superseded by the specific histone Nt-acetyltransferase activities.
human	NAA40	IPR039949	GO:0043998	histone H2A acetyltransferase activity	ACCEPT	no		Core activity; redundant with IDA/IBA H2A annotations.
human	NBR1	IPR000433	GO:0008270	zinc ion binding	KEEP_AS_NON_CORE	yes		Structurally supported (ZZ-type zinc finger with eight coordinating residues) but a structural/cofactor-binding property rather than the receptor's core cargo-bridging function.
human	NCOA4	IPR039947	GO:0003713	transcription coactivator activity	KEEP_AS_NON_CORE	yes		The transcription coactivator activity is a legitimate but secondary function of NCOA4. Modern literature (2023-2024 reviews) emphasizes ferritinophagy as the primary function, with coactivator function being domain-separable (N-terminal vs C-terminal).
human	NCOA4	IPR039947	GO:0006879	intracellular iron ion homeostasis	ACCEPT	no		This is a CORE biological process for NCOA4. By serving as the ferritinophagy cargo receptor, NCOA4 directly regulates intracellular iron availability. Ncoa4-/- mice show profound iron accumulation in splenic macrophages.
human	NDUFS1	IPR000283	GO:0016020	membrane	ACCEPT	no		Correct but very generic. Acceptable for an IEA annotation as a broader parent of the more specific mitochondrial inner membrane annotation.
human	NDUFS1	IPR010228,IPR015405	GO:0016651	oxidoreductase activity, acting on NAD(P)H	ACCEPT	no		Correct classification at an intermediate level. Complex I oxidizes NADH, which falls under the NAD(P)H-acting oxidoreductase class. Acceptable IEA annotation.
human	NDUFS1	IPR000283	GO:0042773	ATP synthesis coupled electron transport	ACCEPT	no		Correct. Complex I function is coupled to ATP synthesis via the proton motive force. This is an appropriate biological process annotation for a Complex I subunit.
human	NDUFS2	IPR001135,IPR014029,IPR022885	GO:0016651	oxidoreductase activity, acting on NAD(P)H	MODIFY	yes	GO:0048038 quinone binding	While Complex I as a whole acts on NADH, NDUFS2 specifically is in the Q-module and interacts with ubiquinone, not NADH. The NADH binding site is on NDUFV1 in the N-module. For NDUFS2 specifically, quinone binding (GO:0048038) is more appropriate. However, as an IEA from InterPro domain mapping to the Complex I 49kDa subunit family, it is not entirely wrong as a complex-level annotation. Should be modified to reflect NDUFS2's actual substrate interaction.
human	NDUFS2	IPR001135	GO:0048038	quinone binding	MODIFY	yes	GO:0048039 ubiquinone binding	NDUFS2 specifically binds ubiquinone (coenzyme Q), not quinones generically. The more specific term GO:0048039 (ubiquinone binding) would be more appropriate given the well-characterized structural evidence of NDUFS2 forming the ubiquinone-binding channel with His59/Tyr108 contacting the ubiquinone headgroup.
human	NDUFS2	IPR001135	GO:0051287	NAD binding	REMOVE	yes		NDUFS2 does not bind NAD or NADH. The NADH-binding site in Complex I is located on the NDUFV1 (51 kDa) subunit in the N-module, which also contains the FMN cofactor. NDUFS2 is in the Q-module and binds ubiquinone, not NADH. This IEA is likely a spurious transfer from the broader Complex I domain family annotation.
human	NDUFS4	IPR006885	GO:0022900	electron transport chain	ACCEPT	no		Correct but broader than the IBA annotation to GO:0022904. As an IEA annotation it provides additional automated support. It is consistent with the known role of NDUFS4 as a Complex I subunit in the electron transport chain.
human	NDUFV1	IPR001949,IPR011537	GO:0010181	FMN binding	ACCEPT	no		"Core molecular function. NDUFV1 binds FMN as a cofactor essential for its catalytic role in NADH oxidation. Confirmed by cryo-EM structure (PMID:28844695) showing FMN bound in the NDUFV1 subunit. UniProt states ""Binds 1 FMN"" with experimental evidence."
human	NDUFV1	IPR011537	GO:0051287	NAD binding	ACCEPT	no		Core molecular function. NDUFV1 is the NADH-binding subunit of Complex I. The NADH binding site is at residues 87-96 (UniProt feature annotation). NADH binding is essential for NDUFV1's catalytic role.
human	NEUROD1	IPR011598,IPR036638	GO:0046983	protein dimerization activity	ACCEPT	no		The HLH domain mediates dimerization. This is a fundamental property of bHLH transcription factors and is experimentally confirmed for NEUROD1 heterodimerizing with E47/TCF12.
human	NEUROD1	IPR016637	GO:0006355	regulation of DNA-templated transcription	ACCEPT	no		This is a very general parent term. NEUROD1 does regulate transcription (specifically, activates it). While less specific than positive regulation terms, this is not incorrect. Acceptable as a general process annotation.
human	NEUROG1	IPR011598,IPR036638	GO:0046983	protein dimerization activity	ACCEPT	no		Accurate inference from domain composition. bHLH proteins require dimerization for DNA binding. NEUROG1 forms heterodimers with E-proteins (TCF4/E12) as documented in UniProtKB and literature.
human	NEUROG2	IPR011598,IPR036638	GO:0046983	protein dimerization activity	ACCEPT	no		Protein dimerization is a fundamental aspect of bHLH transcription factor function. NEUROG2 must form heterodimers with E-proteins to bind DNA effectively. This annotation is mechanistically important for understanding how NEUROG2 achieves its DNA binding activity, though it is a supporting function rather than the primary activity.
human	NFE2L2	IPR047167	GO:0006357	regulation of transcription by RNA polymerase II	ACCEPT	no		Consistent with IBA annotation for this process. NRF2 specifically regulates Pol II transcription.
human	NFIA	IPR000647,IPR020604	GO:0003700	DNA-binding transcription factor activity	ACCEPT	no		Correctly inferred from CTF/NFI domain (IPR000647, IPR020604). While less specific than GO:0000981, this parent term remains valid and appropriate for IEA annotation.
human	NFIA	IPR000647,IPR003619,IPR020604	GO:0006355	regulation of DNA-templated transcription	ACCEPT	no		Valid general biological process term for transcription factor activity. Appropriately inferred from CTF/NFI domain. More specific child terms (GO:0006357) provide additional precision.
human	NFS1	IPR010240	GO:0030170	pyridoxal phosphate binding	ACCEPT	no		PLP binding is essential for cysteine desulfurase catalytic mechanism and is confirmed by crystal structures.
human	NFS1	IPR010240	GO:0044571	[2Fe-2S] cluster assembly	ACCEPT	no		[2Fe-2S] cluster assembly is the primary product of NFS1's function in the ISC complex, well-characterized by cryo-EM and biochemistry.
human	NFU1	IPR001075	GO:0005506	iron ion binding	ACCEPT	no		Iron ion binding is inherent to NFU1's function as an Fe-S cluster scaffold. The [4Fe-4S] cluster contains four iron atoms that are coordinated by the protein. While this is a more general term than [4Fe-4S] cluster binding, it is not incorrect and provides complementary information about metal binding capacity.
human	NFU1	IPR001075	GO:0016226	iron-sulfur cluster assembly	ACCEPT	no		Iron-sulfur cluster assembly is the primary biological process in which NFU1 participates. NFU1 functions as a late-acting scaffold/carrier that assembles [4Fe-4S] clusters and delivers them to target proteins including LIAS.
human	NID1	IPR001881,IPR018097	GO:0005509	calcium ion binding	ACCEPT	no		"This is a legitimate molecular function supported by domain architecture. Nidogen-1 contains calcium-binding EGF-like repeats in the rod domain connecting G2 and G3 globules, as confirmed by InterPro annotations and UniProt features. PMID:2119632 notes ""The molecule binds calcium ions"" as one of nidogen's properties. While not the core bridging function, calcium binding may play a role in maintaining structural integrity."
human	NID1	IPR003886	GO:0007160	cell-matrix adhesion	KEEP_AS_NON_CORE	yes		Similar to cell adhesion (GO:0007155), this represents a consequence of nidogen-1's structural role rather than its direct function. The InterPro NIDO domain (IPR003886) is associated with cell-matrix interactions, but nidogen-1's primary role is as a structural bridge between laminin and collagen IV networks. Cell-matrix adhesion is mediated by the organized basement membrane that nidogen-1 helps assemble. Keep as non-core.
human	NME2	IPR001564	GO:0006228	UTP biosynthetic process	ACCEPT	no		Accepted as the pathway-level consequence of NME2 NDP kinase activity maintaining NTP pools, though individual nucleotides are substrate-specific contexts.
human	NME2	IPR001564	GO:0006241	CTP biosynthetic process	ACCEPT	no		Accepted as the pathway-level consequence of NME2 NDP kinase activity maintaining NTP pools, though individual nucleotides are substrate-specific contexts.
human	NOTCH1	IPR001881,IPR018097	GO:0005509	calcium ion binding	ACCEPT	no		Calcium binding is a core molecular function of NOTCH1. The EGF-like calcium-binding domains (IPR001881) are essential for NOTCH1 structure and function. UniProt lists calcium ion binding in the domain annotations.
human	NOTCH1	IPR022362	GO:0006355	regulation of DNA-templated transcription	ACCEPT	no		Transcriptional regulation is a core downstream function of NOTCH1 signaling. The NICD-RBPJ-MAML complex directly activates transcription of target genes like HES and HEY family members.
human	NOTCH1	IPR008297,IPR010660,IPR011656	GO:0016020	membrane	ACCEPT	no		Generic membrane annotation is correct but less informative than more specific terms (plasma membrane, Golgi membrane, ER membrane) which are also annotated.
human	NOTCH1	IPR022362	GO:0038023	signaling receptor activity	ACCEPT	no		Signaling receptor activity is a core molecular function of NOTCH1. This is the primary role of the protein.
human	NOTCH1	IPR008297	GO:0050793	regulation of developmental process	ACCEPT	no		Developmental regulation is a well-established function of NOTCH1. UniProt notes roles in postimplantation development, mesoderm development, somite formation, and neurogenesis.
human	NOVA2	IPR004087	GO:0003676	nucleic acid binding	MARK_AS_OVER_ANNOTATED	yes	GO:0003723 RNA binding; GO:1990825 sequence-specific mRNA binding	While technically not incorrect (RNA is a nucleic acid), this term is too general for NOVA2. The protein specifically binds RNA through its KH domains, and more informative annotations exist (GO:0003723 RNA binding, GO:0003729 mRNA binding, GO:1990825 sequence-specific mRNA binding). This IEA annotation adds no value beyond what is captured by the more specific terms.
human	NPHS2	IPR001972	GO:0016020	membrane	MODIFY	yes	GO:0005886 plasma membrane	The generic GO:0016020 membrane term is an over-generalization. Podocin has well-characterized localization to the plasma membrane, specifically at the slit diaphragm. The more specific term GO:0005886 plasma membrane should be preferred.
human	NPLOC4	IPR016563	GO:0006511	ubiquitin-dependent protein catabolic process	ACCEPT	no		Core biological-process role; the UFD1-NPL4-VCP complex delivers ubiquitinated substrates for degradation by the proteasome.
human	NRAS	IPR001806	GO:0003924	GTPase activity	ACCEPT	no		Correct InterPro2GO mapping consistent with the IBA/IDA/ISS GTPase activity rows.
human	NRAS	IPR001806,IPR005225,IPR020849	GO:0005525	GTP binding	ACCEPT	no		GTP binding is a core molecular function directly supported by the crystal structure (GDP-bound) and the conserved GTP-binding sites in the UniProt record.
human	NRAS	IPR020849	GO:0007165	signal transduction	KEEP_AS_NON_CORE	yes		Not wrong, but less informative than the specific Ras-signal-transduction terms. Retained as a non-core broad classifier.
human	NRAS	IPR020849	GO:0016020	membrane	MARK_AS_OVER_ANNOTATED	yes		The bare membrane term loses the diagnostic plasma-membrane/Golgi-membrane specificity that is well established for NRAS.
human	OLA1	IPR004396,IPR006073,IPR031167	GO:0005525	GTP binding	KEEP_AS_NON_CORE	yes		OLA1 does bind GTP in a regulated, phospho-state-dependent manner. ATP is the preferred substrate based on structural determinants (G4 motif NxxE, Koller-Eichhorn 2007), but GTP binding/hydrolysis is biologically relevant under phosphorylation control. Marked as non-core because ATPase activity is the predominant baseline function.
human	OLIG2	IPR032658	GO:0006355	regulation of DNA-templated transcription	ACCEPT	no		Correct general term for OLIG2's role as a transcriptional regulator. While more specific terms for positive regulation are also present, this broader term appropriately captures the general function.
human	OLIG2	IPR032658	GO:0021778	oligodendrocyte cell fate specification	ACCEPT	no		"This is a core function of OLIG2. UniProt explicitly states OLIG2 is ""Required for oligodendrocyte and motor neuron specification."" The protein establishes the pMN domain which gives rise to both motor neurons (early) and oligodendrocytes (later). The term ""specification"" (not ""commitment"") is appropriate because OLIG2+ cells retain plasticity to become either cell type depending on developmental context."
human	OLIG2	IPR032658	GO:0030182	neuron differentiation	MODIFY	yes	GO:0021522 spinal cord motor neuron differentiation	While technically correct, OLIG2 specifically promotes motor neuron differentiation, not general neuron differentiation. In fact, OLIG2 antagonizes V2 and V3 interneuron fates. A more specific term would better capture OLIG2's function.
human	OLIG2	IPR032658	GO:0042552	myelination	KEEP_AS_NON_CORE	yes		Myelination is an indirect downstream effect of OLIG2's role in oligodendrocyte specification. OLIG2 specifies oligodendrocyte fate; the resulting oligodendrocytes then myelinate axons. OLIG2 is not expressed in mature myelinating oligodendrocytes and does not directly regulate myelin genes. This is a secondary phenotypic consequence rather than a direct function.
human	OLIG2	IPR011598,IPR036638	GO:0046983	protein dimerization activity	ACCEPT	no		Protein dimerization is essential for bHLH transcription factor function. OLIG2 interacts with NKX2-2 and ZNF488 through its bHLH domain. This is a core molecular function required for DNA binding and transcriptional activity.
human	OLIG2	IPR032658	GO:0048709	oligodendrocyte differentiation	ACCEPT	no		"Oligodendrocyte differentiation is one of the primary functions of OLIG2. UniProt states it ""Functions together with ZNF488 to promote oligodendrocyte differentiation."" This IEA annotation accurately captures a core function."
human	ORMDL3	IPR007203	GO:0016020	membrane	ACCEPT	no		Correct but very generic. More specific ER membrane annotation is also present. This is an acceptable broad IEA.
human	P3H1	IPR006620	GO:0005506	iron ion binding	KEEP_AS_NON_CORE	yes		Accurate cofactor-binding attribute that supports the catalytic MF; structurally demonstrated, but subsidiary to the informative procollagen-proline 3-dioxygenase activity.
human	P3H1	IPR006620	GO:0016705	oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen	KEEP_AS_NON_CORE	yes		Correct but generic; the specific GO:0019797 procollagen-proline 3-dioxygenase activity better captures the core function.
human	P3H1	IPR006620	GO:0031418	L-ascorbic acid binding	KEEP_AS_NON_CORE	yes		Accurate cofactor-binding attribute supporting the catalytic MF; subsidiary to the core dioxygenase activity.
human	P3H1	IPR039575	GO:0032963	collagen metabolic process	ACCEPT	no		Correct biological process; redundant with IBA/ISS.
human	P3H2	IPR006620	GO:0005506	iron ion binding	KEEP_AS_NON_CORE	yes		Accurate catalytic cofactor attribute (Fe cation cofactor; Fe-binding residues in the Fe2OG domain) but a supporting feature rather than the standalone core function.
human	P3H2	IPR006620	GO:0016705	oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen	KEEP_AS_NON_CORE	yes		Correct but generic parent term; the specific GO:0019797 captures the core catalytic activity.
human	P3H2	IPR006620	GO:0031418	L-ascorbic acid binding	KEEP_AS_NON_CORE	yes		Accurate catalytic cofactor attribute (L-ascorbate cofactor; KM=110 uM for ascorbate) but subsidiary to the informative procollagen-proline 3-dioxygenase activity.
human	P4HA1	IPR006620	GO:0005506	iron ion binding	ACCEPT	no		Supported by the UniProt COFACTOR (Fe(2+), one per subunit) and the Fe-binding residues in the Fe2OG domain; a genuine, mechanistically essential molecular function.
human	P4HA1	IPR006620	GO:0016705	oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen	ACCEPT	no		Correct and consistent with the 2-oxoglutarate/O2-dependent dioxygenase mechanism; the more specific GO:0004656 captures the precise core function.
human	P4HA1	IPR006620	GO:0031418	L-ascorbic acid binding	ACCEPT	no		Supported by the UniProt COFACTOR (L-ascorbate) and the Vitamin C keyword; mechanistically required and biologically central (collagen hydroxylation depends on vitamin C).
human	P4HA2	IPR006620	GO:0005506	iron ion binding	ACCEPT	no		Accurate cofactor and active-site chemistry directly supported by the UniProt cofactor line and metal-binding residues; integral to the catalytic mechanism.
human	P4HA2	IPR006620	GO:0016705	oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen	ACCEPT	no		Correct parent of the specific procollagen-proline 4-dioxygenase activity; accurately describes the enzyme oxidoreductase class.
human	P4HA2	IPR006620	GO:0031418	L-ascorbic acid binding	ACCEPT	no		Accurate cofactor binding directly supported by the UniProt cofactor line; mechanistically integral to sustained catalysis.
human	P4HA3	IPR006620	GO:0005506	iron ion binding	ACCEPT	no		Iron coordination (residues 440, 442, 510) is essential for catalysis; correct cofactor molecular function supporting the core activity.
human	P4HA3	IPR006620	GO:0016705	oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen	ACCEPT	no		Accurate general oxidoreductase chemistry; the specific GO:0004656 captures the core function more informatively, but this parent term is not wrong.
human	P4HA3	IPR006620	GO:0031418	L-ascorbic acid binding	ACCEPT	no		Correct cofactor-binding molecular function supporting the core dioxygenase activity.
human	PAM16	IPR005341	GO:0005744	TIM23 mitochondrial import inner membrane translocase complex	MODIFY	yes	GO:0001405 PAM complex, Tim23 associated import motor	Use the PAM complex term for PAM16 complex membership; TIM23 is the coupled translocase.
human	PAM16	IPR005341	GO:0030150	protein import into mitochondrial matrix	ACCEPT	no		Correct and core. PAM16 regulates the PAM motor that powers TIM23-mediated matrix import.
human	PANK4	IPR004567	GO:0005524	ATP binding	KEEP_AS_NON_CORE	yes		Plausible nucleotide binding by the kinase-like fold, but not the demonstrated catalytic activity (which is metal-dependent phosphatase). Non-core.
human	PANK4	IPR004567,IPR015844	GO:0015937	coenzyme A biosynthetic process	KEEP_AS_NON_CORE	yes		Correct pathway association via the phosphatase activity, but PANK4 modulates rather than performs core CoA biosynthesis; non-core.
human	PAX6	IPR001523,IPR017970,IPR043565	GO:0006355	regulation of DNA-templated transcription	ACCEPT	no		Correct parent-level process term; concordant with experimental data, acceptable as a broad electronic annotation.
human	PCSK1N	IPR010832	GO:0004866	endopeptidase inhibitor activity	KEEP_AS_NON_CORE	yes		InterPro2GO mapping is correct but redundant with the more specific GO:0004867 already present. Retained but not core.
human	PDCD5	IPR002836,IPR036883	GO:0003677	DNA binding	UNDECIDED	yes		The annotation is based on domain homology but lacks direct experimental validation. PDCD5 functions primarily through protein-protein interactions (with Tip60, p53, MDM2, FOXP3, CCT) rather than direct DNA binding. The ChIP experiment in PMID:22914926 shows PDCD5 association at the p21 promoter, but this may be indirect through p53 binding rather than direct DNA binding.
human	PDGFA	IPR000072,IPR006782	GO:0016020	membrane	KEEP_AS_NON_CORE	yes		PDGF-A is synthesized and processed through the secretory pathway, but its core function is extracellular receptor-ligand signaling.
human	PDGFB	IPR000072,IPR006782	GO:0016020	membrane	KEEP_AS_NON_CORE	yes		Membrane is too broad for PDGFB; any membrane association is a precursor/retention or receptor-bound context, so keep only as non-core.
human	PELO	IPR004405	GO:0070481	nuclear-transcribed mRNA catabolic process, non-stop decay	ACCEPT	no		NSD is a genuine PELO process; the InterPro IEA is corroborated by direct evidence in mammalian cells.
human	PELO	IPR004405	GO:0070966	nuclear-transcribed mRNA catabolic process, no-go decay	ACCEPT	no		NGD is a core PELO process, supported by direct experimental annotations.
human	PELO	IPR004405	GO:0071025	RNA surveillance	KEEP_AS_NON_CORE	yes		Correct but a parent of the specific no-go/non-stop decay terms; retained as a less-informative general annotation.
human	PEX1	IPR003959,IPR003960	GO:0016887	ATP hydrolysis activity	ACCEPT	no		ATP hydrolysis activity is a core function of PEX1. This IEA annotation is consistent with the IBA and IMP annotations.
human	PEX10	IPR025654	GO:0016558	protein import into peroxisome matrix	ACCEPT	no		Correct automated annotation, redundant with IBA and experimental annotations.
human	PEX11A	IPR008733	GO:0016559	peroxisome fission	ACCEPT	no		The PEX11 domain (IPR008733/PF05648) is specifically associated with peroxisome fission function. This IEA is consistent with the IBA and IDA annotations for the same term.
human	PEX11B	IPR008733	GO:0016559	peroxisome fission	ACCEPT	no		Correct mapping. The PEX11 domain is functionally associated with peroxisome fission, well supported by experimental evidence.
human	PEX11G	IPR008733	GO:0016559	peroxisome fission	ACCEPT	no		The InterPro-based annotation is correct. PEX11G belongs to the PEX11 family (IPR008733, Pfam PF05648) which is functionally characterized as involved in peroxisome fission/proliferation.
human	PEX12	IPR017375	GO:0016558	protein import into peroxisome matrix	ACCEPT	no		This is a core function annotation consistent with all other evidence.
human	PEX13	IPR007223,IPR035463	GO:0016020	membrane	ACCEPT	no		PEX13 is an integral membrane protein. This is a broad IEA that is subsumed by more specific peroxisomal membrane annotations but is not incorrect.
human	PEX13	IPR007223,IPR035463	GO:0016560	protein import into peroxisome matrix, docking	ACCEPT	no		Correctly maps the InterPro domain information to the core docking function.
human	PEX2	IPR025654	GO:0016558	protein import into peroxisome matrix	ACCEPT	no		Core function. PEX2 is required for peroxisomal matrix protein import through its role in PEX5 receptor recycling. IEA annotation consistent with experimental evidence.
human	PEX26	IPR010797	GO:0044877	protein-containing complex binding	ACCEPT	no		PEX26 does bind a protein-containing complex (the PEX1-PEX6 heterohexamer). This IEA is consistent with experimental evidence from PMID:16854980 showing PEX26 binds the assembled PEX1-PEX6 complex. While ATPase binding (GO:0051117) is more specific, this broader term is acceptable for an IEA annotation.
human	PEX26	IPR010797	GO:0045046	protein import into peroxisome membrane	REMOVE	yes		PEX26 is not involved in importing proteins into the peroxisomal membrane. PEX26's role is in peroxisomal matrix protein import via receptor recycling. PEX26 is itself a substrate of the PEX19/PEX3 PMP import pathway (PMID:16763195), but it does not facilitate PMP import for other proteins. This IEA annotation likely results from an overly broad InterPro domain annotation.
human	PEX6	IPR003959,IPR003960	GO:0016887	ATP hydrolysis activity	ACCEPT	no		Correct IEA annotation. ATP hydrolysis activity is a core function of PEX6, supported by domain structure and mutagenesis data (PMID:16854980). Duplicates the IBA and IMP annotations for the same term.
human	PEX7	IPR044536	GO:0005053	peroxisome matrix targeting signal-2 binding	ACCEPT	no		The InterPro-based mapping is correct. PEX7 is indeed the PTS2 receptor. This IEA annotation is concordant with the IBA and IDA annotations for the same term.
human	PFDN1	IPR002777	GO:0006457	protein folding	ACCEPT	no		The IEA annotation to protein folding via InterPro is correct and consistent with the higher-confidence IBA and IDA annotations. The prefoldin beta-like domain (IPR002777) is specifically associated with the protein folding function of the prefoldin complex (PMID:9630229, PMID:30955883).
human	PFDN1	IPR002777	GO:0016272	prefoldin complex	ACCEPT	no		PFDN1 is a core structural subunit of the prefoldin complex. The IEA mapping from the prefoldin beta-like domain (IPR002777) to prefoldin complex membership is appropriate and consistent with experimental evidence (PMID:9630229, PMID:30955883).
human	PFDN1	IPR002777	GO:0051082	unfolded protein binding	MODIFY	yes	GO:0044183 protein folding chaperone	"GO:0051082 is being obsoleted. While the InterPro mapping correctly identifies that the prefoldin domain binds unfolded proteins, the replacement term GO:0044183 ""protein folding chaperone"" better captures the functional role of prefoldin as a chaperone that assists in protein folding by delivering unfolded substrates to the TRiC/CCT chaperonin (PMID:32699605, PMID:9630229)."
human	PFDN2	IPR002777,IPR027235	GO:0006457	protein folding	ACCEPT	no		Redundant with IBA and IDA annotations for the same term. The InterPro-based mapping is correct and consistent with the known function of prefoldin.
human	PFDN2	IPR002777,IPR027235	GO:0016272	prefoldin complex	ACCEPT	no		Core cellular component. PFDN2 is a structural subunit of the prefoldin complex, confirmed by multiple structures and biochemical characterization.
human	PFDN2	IPR002777	GO:0051082	unfolded protein binding	MODIFY	yes	GO:0044183 protein folding chaperone	"GO:0051082 ""unfolded protein binding"" describes only the binding aspect. The correct MF term for prefoldin is GO:0044183 ""protein folding chaperone"" which captures the complete holdase/transfer chaperone function. The IBA already uses GO:0044183."
human	PFDN4	IPR002777,IPR016661	GO:0006457	protein folding	ACCEPT	no		The IEA annotation to protein folding via InterPro is correct and consistent with the higher-confidence IBA and IDA annotations. The prefoldin beta-like domain (IPR002777) is specifically associated with the protein folding function of the prefoldin complex (PMID:9630229, PMID:30955883).
human	PFDN4	IPR002777,IPR016661	GO:0016272	prefoldin complex	ACCEPT	no		PFDN4 is a core structural subunit of the prefoldin complex. The IEA mapping from the prefoldin beta-like domain (IPR002777) to prefoldin complex membership is appropriate and consistent with experimental evidence (PMID:9630229, PMID:30955883).
human	PFDN4	IPR002777	GO:0051082	unfolded protein binding	MODIFY	yes	GO:0044183 protein folding chaperone	"GO:0051082 is being obsoleted. While the InterPro mapping correctly identifies that the prefoldin domain binds unfolded proteins, the replacement term GO:0044183 ""protein folding chaperone"" better captures the functional role of prefoldin as a chaperone that assists in protein folding by delivering unfolded substrates to the TRiC/CCT chaperonin (PMID:9630229, PMID:30955883)."
human	PFDN5	IPR011599	GO:0006457	protein folding	ACCEPT	no		The IEA annotation to protein folding via InterPro is correct and consistent with the higher-confidence IDA and NAS annotations. The prefoldin alpha domain (IPR011599) is specifically associated with the protein folding function of the prefoldin complex (PMID:9630229, PMID:30955883).
human	PFDN5	IPR011599	GO:0016272	prefoldin complex	ACCEPT	no		PFDN5 is a core structural subunit of the prefoldin complex. The IEA mapping from the prefoldin alpha domain (IPR011599) to prefoldin complex membership is appropriate and consistent with experimental evidence (PMID:9630229, PMID:30955883).
human	PFDN5	IPR011599	GO:0051082	unfolded protein binding	MODIFY	yes	GO:0044183 protein folding chaperone	"GO:0051082 is being obsoleted. The term describes only a binding activity and does not capture the chaperone function of prefoldin. GO:0044183 ""protein folding chaperone"" (defined as ""Binding to a protein or a protein-containing complex to assist the protein folding process"") is the recommended replacement (PMID:9630229, PMID:30955883)."
human	PFDN6	IPR002777	GO:0006457	protein folding	ACCEPT	no		The IEA mapping from the PFD_beta-like domain to protein folding is appropriate and consistent with the experimentally determined function. Redundancy with other evidence codes is acceptable.
human	PFDN6	IPR002777	GO:0016272	prefoldin complex	ACCEPT	no		The IEA mapping from the prefoldin beta domain to prefoldin complex membership is appropriate and consistent with multiple other lines of evidence.
human	PFDN6	IPR002777	GO:0051082	unfolded protein binding	MODIFY	yes	GO:0044183 protein folding chaperone	"Prefoldin does not merely bind unfolded proteins passively; it actively functions as a co-chaperone that captures non-native substrates and delivers them to TRiC/CCT. GO:0044183 ""protein folding chaperone"" (defined as ""Binding to a protein or a protein-containing complex to assist the protein folding process"") better describes this active molecular function."
human	PHTF1	IPR039775	GO:0005783	endoplasmic reticulum	MODIFY	yes	GO:0005789 endoplasmic reticulum membrane	While PHTF1 is indeed associated with the ER, as an integral multi-pass membrane protein with 8 transmembrane helices, it specifically resides in the ER membrane rather than the ER lumen or general ER. The more specific term GO:0005789 (endoplasmic reticulum membrane) is already annotated and is more accurate for this protein. Experimental evidence from Oyhenart et al. (2005) demonstrated ER localization using carbonate extraction (confirming integral membrane protein status) and immunofluorescence colocalization with ER markers in rodent germ cells.
human	PHYKPL	IPR005814	GO:0008483	transaminase activity	REMOVE	yes		"Incorrect annotation. PMID:22241472 explicitly states: ""Unlike AGXT2, AGXT2L1 and AGXT2L2 did not act as transaminases."" Despite belonging to the aminotransferase III family, PHYKPL functions as an ammoniophospholyase, not a transaminase. The UniProt entry also cautions: ""Does not seem to possess aminotransferase activity."""
human	PHYKPL	IPR005814	GO:0030170	pyridoxal phosphate binding	ACCEPT	no		"Correctly annotated. PMID:22241472: ""AGXT2L1 and AGXT2L2 catalyzed the pyridoxal-phosphate-dependent breakdown of phosphoethanolamine and 5-phosphohydroxy-L-lysine."" The enzyme requires PLP as an essential cofactor."
human	PICK1	IPR010504	GO:0019904	protein domain specific binding	ACCEPT	no		protein domain specific binding is supported as part of PICK1 PDZ/BAR scaffold, membrane-remodeling, or synaptic receptor-trafficking function.
human	PIK3C3	IPR008290,IPR015433	GO:0046854	phosphatidylinositol phosphate biosynthetic process	MODIFY	yes	GO:0036092 phosphatidylinositol-3-phosphate biosynthetic process	Human VPS34 is specifically responsible for generating phosphatidylinositol 3-phosphate rather than phosphatidylinositol phosphates in general.
human	PIK3CD	IPR015433	GO:0046854	phosphatidylinositol phosphate biosynthetic process	ACCEPT	no		PIK3CD produces 3-phosphoinositides, especially PIP3, as the biochemical product of its class IA lipid kinase activity. This process term is broader than an ideal PIP3-biosynthesis term but is correct.
human	PIK3R4	IPR000719,IPR008271	GO:0004672	protein kinase activity	KEEP_AS_NON_CORE	yes		Keep as non-core rather than making it the main functional claim. The dominant biological role of PIK3R4 is regulatory/scaffolding contribution to PI3KC3 complex lipid kinase activity; the protein-kinase annotation remains secondary and mechanistically debated.
human	PIK3R4	IPR000719	GO:0005524	ATP binding	KEEP_AS_NON_CORE	yes		Keep as non-core. ATP binding follows from the kinase-domain/protein-kinase annotation, whereas the central gene function is scaffolding/regulatory contribution to PI3KC3 lipid kinase complexes.
human	PIK3R4	IPR045162	GO:0016236	macroautophagy	ACCEPT	no		Accept as core process. PIK3R4/VPS15 is a PI3KC3-C1 component; class III PI3K activity and the Vps34/Vps15/ATG14/BECN1 complex support canonical autophagy initiation.
human	PIK3R4	IPR045162	GO:0045324	late endosome to vacuole transport	MODIFY	yes	GO:0045022 early endosome to late endosome transport	Modify to early endosome to late endosome transport. Human evidence supports Rab7-linked hVPS34/p150 cycling between early and late endosomes rather than a vacuole-specific transport step.
human	PIP5K1B	IPR002498	GO:0046488	phosphatidylinositol metabolic process	MODIFY	yes	GO:0046854 phosphatidylinositol phosphate biosynthetic process	Replace the broad phosphatidylinositol metabolic/biosynthetic process with phosphatidylinositol phosphate biosynthetic process.
human	PIP5K1B	IPR002498	GO:0052742	phosphatidylinositol kinase activity	MODIFY	yes	GO:0016308 1-phosphatidylinositol-4-phosphate 5-kinase activity	Use the specific 1-phosphatidylinositol-4-phosphate 5-kinase activity term.
human	PIWIL1	IPR003165,IPR036397	GO:0003676	nucleic acid binding	REMOVE	yes		"Overly generic and uninformative. PIWIL1 specifically binds piRNAs, not nucleic acids in general. The more specific term ""piRNA binding"" (GO:0034584) already captures this function accurately. Generic IEA annotations should be removed when specific experimental evidence exists."
human	PKM	IPR001697,IPR015793	GO:0000287	magnesium ion binding	ACCEPT	no		Mg2+ is an essential cofactor for pyruvate kinase activity. Both isoforms require this ion.
human	PKM	IPR001697,IPR015793	GO:0030955	potassium ion binding	ACCEPT	no		K+ is an essential cofactor for pyruvate kinase activity. Both isoforms require this ion.
human	PLD3	IPR001736	GO:0003824	catalytic activity	KEEP_AS_NON_CORE	yes	GO:0045145 single-stranded DNA 5'-3' DNA exonuclease activity	"While accurate, this term is too broad. More specific molecular function terms like ""single-stranded DNA 5'-3' DNA exonuclease activity"" (GO:0045145) are available and should be preferred."
human	PLD4	IPR001736	GO:0003824	catalytic activity	MODIFY	yes	GO:0045145 single-stranded DNA 5'-3' DNA exonuclease activity	This term is too general to be useful. PLD4's specific catalytic activity is single-stranded DNA 5'-3' exonuclease activity (GO:0045145).
human	PLD5	IPR001736	GO:0003824	catalytic activity	REMOVE	yes		"PLD5 is explicitly designated as ""Inactive phospholipase D5"" by UniProt due to degenerate HKD catalytic motifs. Multiple reviews confirm PLD5 lacks phospholipase activity. Nelson and Frohman (2015) state PLD5 has ""no catalytic activity"" as a lipase. Bozatzi and Sapkota (2018) confirm PLD5 is ""catalytically inactive"" due to lacking HKD motifs. A 2023 structural analysis states ""Little is known about PLD5, and it is even unclear if it is active as an enzyme."" While the protein contains the PLD domain architecture, this IEA annotation incorrectly implies active catalytic function. The presence of a catalytic domain does not guarantee enzymatic activity - many pseudoenzymes exist."
human	PMPCA	IPR001431	GO:0004222	metalloendopeptidase activity	MODIFY	yes	GO:0030674 protein-macromolecule adaptor activity	As an enabled molecular function on PMPCA alone, metalloendopeptidase activity overstates the alpha subunit. Replace the direct enabled MF with protein-macromolecule adaptor activity and represent complex protease activity as contributes_to in core_functions.
human	PMPCA	IPR001431	GO:0006508	proteolysis	MODIFY	yes	GO:0016485 protein processing	Use protein processing to capture the maturation of imported mitochondrial precursor proteins rather than broad proteolysis.
human	PMPCA	IPR011249	GO:0046872	metal ion binding	REMOVE	yes		The available evidence does not support metal ion binding as a direct PMPCA activity; this appears to be propagated from the complex/beta subunit metalloprotease mechanism.
human	PMPCB	IPR001431	GO:0006508	proteolysis	MARK_AS_OVER_ANNOTATED	yes		Prefer metalloendopeptidase activity and protein processing/presequence-cleavage terms over generic proteolysis.
human	PMPCB	IPR011249	GO:0046872	metal ion binding	MARK_AS_OVER_ANNOTATED	yes		Prefer metalloendopeptidase activity over generic metal ion binding.
human	POLD2	IPR007185	GO:0003677	DNA binding	MARK_AS_OVER_ANNOTATED	yes		"IEA from InterPro. POLD2 in isolation has not been shown to bind DNA directly; the cocrystal structure of POLD2 with the POLD3 NTD shows ""a primarily negatively charged molecular surface without obvious features for DNA binding"" (Lee et al. 2014). DNA contacts in Polδ are dominated by POLD1/POLD3. This is a generic IEA that is at best indirect; mark as over-annotated."
human	POLDIP2	IPR011722,IPR036623	GO:0003677	DNA binding	UNDECIDED	yes		The hemimethylated DNA-binding domain is present, but its functional significance in POLDIP2 is not established experimentally. The protein's characterized functions involve binding to polymerases and PCNA rather than direct DNA binding. More experimental evidence is needed.
human	POLE4	IPR009072	GO:0046982	protein heterodimerization activity	ACCEPT	no		Core structural function.
human	POMT1	IPR003342	GO:0000030	mannosyltransferase activity	ACCEPT	no		Core function.
human	POMT1	IPR003342	GO:0006493	protein O-linked glycosylation	ACCEPT	no		Duplicate of IBA annotation.
human	POMT1	IPR003342	GO:0016020	membrane	ACCEPT	no		General membrane localization.
human	PPP2CA	IPR004843,IPR006186	GO:0016787	hydrolase activity	ACCEPT	no		This is a correct but very broad parent term. PPP2CA is a hydrolase (phosphoester hydrolysis). More specific terms (GO:0004722) are also annotated, but this IEA annotation from InterPro is not wrong.
human	PPP2CB	IPR004843,IPR006186	GO:0016787	hydrolase activity	ACCEPT	no		While very broad, hydrolase activity is technically correct as a parent of phosphatase activity. The more specific GO:0004722 annotations also exist. This IEA is acceptable as a domain-based annotation even though more informative terms are present.
human	PPP3CA	IPR004843,IPR006186	GO:0016787	hydrolase activity	MODIFY	yes	GO:0004722 protein serine/threonine phosphatase activity; GO:0033192 calmodulin-dependent protein phosphatase activity	A more specific phosphatase term better represents known catalytic chemistry for calcineurin A alpha.
human	PPP3CA	IPR043360	GO:0097720	calcineurin-mediated signaling	ACCEPT	no		This is a core pathway-level annotation aligned with extensive calcineurin literature.
human	PPP3CB	IPR043360	GO:0097720	calcineurin-mediated signaling	ACCEPT	no		ACCEPT. Calcineurin-mediated signaling is a core function. Redundant with IBA but correct.
human	PRDX4	IPR019479	GO:0051920	peroxiredoxin activity	ACCEPT	no		This is the core molecular function of PRDX4 and is supported by both the original thioredoxin peroxidase study and structural/catalytic analysis.
human	PRG2	IPR002352	GO:0006955	immune response	ACCEPT	no		Core function in immune defense, experimentally validated in helminth killing.
human	PRG3	IPR002352	GO:0006955	immune response	ACCEPT	no		Core immune function.
human	PRRT1	IPR007593	GO:0016020	membrane	ACCEPT	no		PRRT1 contains a transmembrane helix (residues 224-244 per UniProt FT annotation) and is classified as a single-pass type II membrane protein. The IEA annotation from InterPro is technically accurate, if broad. More specific annotations (recycling endosome, early endosome, glutamatergic synapse) provide better localization information.
human	PSMA1	IPR000426	GO:0006511	ubiquitin-dependent protein catabolic process	MODIFY	yes	GO:0043161 proteasome-mediated ubiquitin-dependent protein catabolic process	Replace the broad annotation with proteasome-mediated ubiquitin-dependent protein catabolic process, which better captures the gene product role supported by proteasome literature and existing specific GOA annotations.
human	PSMA1	IPR000426,IPR035144	GO:0019773	proteasome core complex, alpha-subunit complex	ACCEPT	no		Structural studies and UniProt summaries place the protein in the 20S proteasome core; this complex-membership annotation is central to the gene product role.
human	PSMA1	IPR001353	GO:0030163	protein catabolic process	MODIFY	yes	GO:0010498 proteasomal protein catabolic process	Replace the broad annotation with proteasomal protein catabolic process, which better captures the gene product role supported by proteasome literature and existing specific GOA annotations.
human	PSMB5	IPR000243	GO:0004298	threonine-type endopeptidase activity	ACCEPT	no		The mature PSMB5 chain begins at Thr60, annotated as the nucleophilic active-site residue, and structural/activity studies support beta5 chymotrypsin-like proteasome activity.
human	PSMB5	IPR000243,IPR001353,IPR016050	GO:0030163	protein catabolic process	MODIFY	yes	GO:0010498 proteasomal protein catabolic process	Replace the broad annotation with proteasomal protein catabolic process, which better captures the gene product role supported by proteasome literature and existing specific GOA annotations.
human	PTEN	IPR045101	GO:0016791	phosphatase activity	ACCEPT	no		Accurate as a parent term, though more specific annotations exist.
human	PTEN	IPR017361	GO:0046856	phosphatidylinositol dephosphorylation	ACCEPT	no		Consistent with IBA annotation. This is a core process term for PTEN's primary function.
human	PTEN	IPR017361	GO:0051800	phosphatidylinositol-3,4-bisphosphate 3-phosphatase activity	ACCEPT	no		This is a documented enzymatic activity of PTEN (PMID:9811831).
human	PTGES3	IPR045250	GO:0051879	Hsp90 protein binding	ACCEPT	no		Hsp90 protein binding is a core function of PTGES3 well documented by multiple experimental studies (PMID:10543959, PMID:10811660, PMID:21183720). The IEA annotation from InterPro is concordant with IBA and IPI annotations.
human	PTPN22	IPR047170	GO:0004726	non-membrane spanning protein tyrosine phosphatase activity	ACCEPT	no		This is the most specific molecular function term for PTPN22 and is fully accurate. PTPN22 is a non-receptor (non-membrane spanning) PTP. The InterPro mapping correctly identifies this specificity.
human	PTPN22	IPR016276	GO:0050856	regulation of T cell receptor signaling pathway	ACCEPT	no		Accurate annotation. Regulation of TCR signaling is a core function of PTPN22. The more specific term GO:0050860 (negative regulation of TCR signaling) is also annotated with IDA evidence. This IEA parent term is acceptable.
human	PUS3	IPR001406,IPR020097,IPR020103	GO:0001522	pseudouridine synthesis	MARK_AS_OVER_ANNOTATED	yes		This annotation is technically correct but overly general. PUS3 specifically synthesizes pseudouridine in tRNAs, not in all RNA types. The more specific GO:0031119 provides better functional information.
human	PUS3	IPR001406,IPR020094,IPR020095,IPR020097,IPR020103	GO:0003723	RNA binding	MODIFY	yes	GO:0000049 tRNA binding	PUS3 does bind RNA, but specifically binds tRNA substrates as a stand-alone enzyme. The general 'RNA binding' term doesn't convey the specificity of PUS3's substrate recognition.
human	PUS3	IPR001406,IPR020097,IPR020103	GO:0009451	RNA modification	MARK_AS_OVER_ANNOTATED	yes		This annotation is correct but overly broad. PUS3 specifically modifies tRNAs by pseudouridylation. More specific terms like GO:0031119 (tRNA pseudouridine synthesis) provide better functional resolution.
human	RAB15	IPR001806,IPR041826	GO:0003924	GTPase activity	ACCEPT	no		RAB15 has EC:3.6.5.2 assigned based on sequence similarity and domain architecture. The catalytic GTPase activity is fundamental to its function in membrane trafficking, cycling between GTP-bound (active) and GDP-bound (inactive) states.
human	RAB15	IPR041826	GO:0032482	Rab protein signal transduction	ACCEPT	no		Appropriate annotation for RAB15's role as a regulatory GTPase. RAB15 participates in signaling networks with other Rabs (Rab5, Rab4, Rab11, Rab27) to coordinate membrane trafficking events.
human	RAB24	IPR001806,IPR041828	GO:0003924	GTPase activity	ACCEPT	no		RAB24 is a Rab small GTPase; the evidence also cautions that it has unusually low GTP hydrolysis and is predominantly GTP-bound, but this does not negate the Rab GTPase/GTP-binding molecular-function annotation.
human	RAB24	IPR001806,IPR005225	GO:0005525	GTP binding	ACCEPT	no		RAB24 is a Rab small GTPase; the evidence also cautions that it has unusually low GTP hydrolysis and is predominantly GTP-bound, but this does not negate the Rab GTPase/GTP-binding molecular-function annotation.
human	RAB7A	IPR001806	GO:0003924	GTPase activity	ACCEPT	no		Core molecular function. GTPase activity is fundamental to RAB7A function as a molecular switch controlling membrane trafficking.
human	RAB7B	IPR001806	GO:0003924	GTPase activity	ACCEPT	no		GTPase activity is the core molecular function of RAB7B. The protein cycles between GTP-bound (active) and GDP-bound (inactive) states.
human	RAB9A	IPR001806,IPR041824	GO:0003924	GTPase activity	ACCEPT	no		Core molecular function. RAB9A hydrolyzes GTP to GDP as part of its regulatory cycle. This is supported by experimental evidence (PMID:15263003).
human	RAB9A	IPR041824	GO:0032482	Rab protein signal transduction	ACCEPT	no		Appropriate biological process annotation. RAB9A participates in Rab-mediated signal transduction to regulate membrane trafficking.
human	RAB9B	IPR001806,IPR041824	GO:0003924	GTPase activity	ACCEPT	no		RAB9B is assigned EC 3.6.5.2 (small monomeric GTPase) in UniProt. Crystal structure (PDB:2OCB) shows RAB9B bound to GTP analog and Mg2+, confirming the active site architecture for GTP hydrolysis. This is a core molecular function.
human	RAB9B	IPR041824	GO:0032482	Rab protein signal transduction	ACCEPT	no		This annotation accurately describes RAB9B function as a Rab GTPase that transduces signals through cycling between GDP and GTP-bound states. IEA from InterPro domain mapping is appropriate.
human	RACK1	IPR045223	GO:0043022	ribosome binding	ACCEPT	no		Correct core molecular function for an integral 40S protein; agrees with IDA/IBA ribosome-binding evidence.
human	RACK1	IPR045223	GO:0045182	translation regulator activity	KEEP_AS_NON_CORE	yes		Broad but accurate MF; the more specific core functions are ribosome binding and the structural/RQC roles.
human	RAD18	IPR039577	GO:0003697	single-stranded DNA binding	ACCEPT	no		The IEA annotation is validated by experimental evidence. ssDNA binding is a more specific annotation than general DNA binding and accurately reflects RAD18's substrate preference.
human	RAD18	IPR039577	GO:0006301	DNA damage tolerance	ACCEPT	no		Correct annotation, duplicative with IBA evidence but acceptable.
human	RAD18	IPR039577	GO:0006513	protein monoubiquitination	ACCEPT	no		Correct annotation, duplicative with IBA evidence.
human	RARA	IPR001628,IPR003078,IPR013088	GO:0006355	regulation of DNA-templated transcription	MODIFY	yes	GO:0045944 positive regulation of transcription by RNA polymerase II; GO:0000122 negative regulation of transcription by RNA polymerase II	RARA directly regulates RNA polymerase II target genes through ligand-dependent activation and unliganded repression; the parent term is less informative.
human	RARA	IPR003078	GO:0048384	retinoic acid receptor signaling pathway	ACCEPT	no		Retinoic acid receptor signaling is the direct pathway in which RARA transduces retinoid ligand binding into RARE-bound transcriptional regulation.
human	RASA2	IPR037773	GO:0005543	phospholipid binding	ACCEPT	no		Important accessory function for membrane localization. The PH domain enables recruitment to PIP3-enriched membranes where active RAS signaling occurs. The C2 domains provide additional lipid-binding capacity.
human	RASA2	IPR001562	GO:0035556	intracellular signal transduction	ACCEPT	no		Core function in signal transduction. RASA2 terminates RAS signaling by catalyzing GTP hydrolysis, which is a fundamental intracellular signaling mechanism.
human	RASA2	IPR037773	GO:0046580	negative regulation of Ras protein signal transduction	ACCEPT	no		Core biological process. This term accurately captures the primary regulatory role of RASA2 in attenuating RAS signaling cascades.
human	RASA3	IPR001562	GO:0035556	intracellular signal transduction	ACCEPT	no		Accurate biological process annotation. RASA3 regulates multiple intracellular signaling cascades including Ras-MAPK and Rap1-integrin pathways. While somewhat redundant with GO:1902531, this is the more general parent term and is correctly applied.
human	RASA3	IPR037774	GO:0046580	negative regulation of Ras protein signal transduction	ACCEPT	no		Core biological function. This precisely captures RASA3's role as a RasGAP that turns off Ras signaling. Loss of RASA3 function leads to elevated Ras-GTP levels and hyperactive MAPK signaling, as demonstrated in mouse scat mutant and human patients with biallelic RASA3 mutations causing Rasopathy-like syndrome.
human	RASA4	IPR037777	GO:0005543	phospholipid binding	ACCEPT	no		Critical for CAPRI function. C2 domains mediate Ca2+-dependent phospholipid binding required for membrane translocation and activation.
human	RASA4	IPR001562	GO:0035556	intracellular signal transduction	ACCEPT	no		Accurate annotation. CAPRI functions in intracellular signal transduction by modulating Ras activity downstream of calcium signals.
human	RASA4	IPR037777	GO:0046580	negative regulation of Ras protein signal transduction	ACCEPT	no		Core function. This is the primary biological role of CAPRI - to negatively regulate Ras signaling in response to calcium signals.
human	RASA4	IPR037777	GO:0071277	cellular response to calcium ion	ACCEPT	no		Core regulatory mechanism. CAPRI is defined by its calcium-dependent activation and translocation, making this annotation central to its identity.
human	RASA4B	IPR037777	GO:0005543	phospholipid binding	ACCEPT	no		Membrane recruitment mechanism.
human	RASA4B	IPR001562	GO:0035556	intracellular signal transduction	ACCEPT	no		Signaling pathway role.
human	RASA4B	IPR037777	GO:0046580	negative regulation of Ras protein signal transduction	ACCEPT	no		Core function.
human	RASA4B	IPR037777	GO:0071277	cellular response to calcium ion	ACCEPT	no		Calcium-sensing mechanism.
human	RASAL1	IPR001562	GO:0035556	intracellular signal transduction	ACCEPT	no		This is a core biological process for RASAL1. The annotation is broader than GO:0046580 (negative regulation of Ras protein signal transduction) but is still accurate and acceptable for an IEA annotation.
human	RASAL1	IPR037776	GO:0046580	negative regulation of Ras protein signal transduction	ACCEPT	no		This is the core biological process function of RASAL1. The protein accelerates Ras-GTP to Ras-GDP conversion, thereby negatively regulating Ras signaling. This annotation is highly specific and accurate.
human	RASAL1	IPR037776	GO:0071277	cellular response to calcium ion	ACCEPT	no		This is a core regulatory mechanism for RASAL1 function. The C2 domains mediate Ca2+-dependent membrane translocation, coupling calcium signaling to Ras regulation. Extensive live-cell imaging studies support this annotation.
human	RB1	IPR028309	GO:0006357	regulation of transcription by RNA polymerase II	ACCEPT	no		Canonical RB1 function/localization, well supported by experimental evidence already present in this file (PMID:7923370 RB-BRG1 cooperation; IDA/EXP rows in this annotation set) and by independent Reactome TAS rows previously ACCEPTed in PRs #440/#444. Mechanical IEA-canonical batch (batch 5 of #347).
human	RBFOX3	IPR047131	GO:0000381	regulation of alternative mRNA splicing, via spliceosome	ACCEPT	no		Core function of RBFOX3 - well-documented regulation of alternative splicing through position-dependent binding to (U)GCAUG motifs
human	RBFOX3	IPR047131	GO:0007399	nervous system development	ACCEPT	no		Well-supported - RBFOX3 is essential for neuronal differentiation and CNS development (PMID:23420872, file:human/RBFOX3/RBFOX3-deep-research.md)
human	RFT1	IPR007594	GO:0006488	dolichol-linked oligosaccharide biosynthetic process	ACCEPT	no		This process annotation is accurate. RFT1 functions in LLO biosynthesis by catalyzing the essential translocation step that allows completion of the oligosaccharide assembly in the ER lumen. Without RFT1 function, LLO biosynthesis is blocked at the M5GN2 stage.
human	RFT1	IPR007594	GO:0016020	membrane	KEEP_AS_NON_CORE	yes		While technically correct (RFT1 is a membrane protein), this annotation is overly general. The more specific GO:0005789 (endoplasmic reticulum membrane) annotations better capture the actual localization. Retained as it does not conflict with more specific annotations.
human	RNF14	IPR031127	GO:0004842	ubiquitin-protein transferase activity	MODIFY	yes	GO:0061630 ubiquitin protein ligase activity	This generic transferase term is correct but less precise than the experimentally established ubiquitin protein ligase activity (GO:0061630). Generalize/replace with the specific ligase activity term that is supported by IDA evidence.
human	RNF14	IPR002867,IPR047548	GO:0008270	zinc ion binding	KEEP_AS_NON_CORE	yes		Zinc binding is a structural feature of the RBR zinc fingers; it is a true molecular property but is supportive/structural rather than the informative catalytic function.
human	RNF185	IPR045103	GO:0005783	endoplasmic reticulum	ACCEPT	no		Correct compartment; redundant with the more specific ER membrane annotations and IDA evidence.
human	RNF185	IPR045103	GO:0006511	ubiquitin-dependent protein catabolic process	ACCEPT	no		Correct but generic; the specific GO:0036503 (ERAD pathway) better captures the core biological role.
human	RNF185	IPR018957	GO:0046872	metal ion binding	KEEP_AS_NON_CORE	yes		Accurate structural feature of the RING domain but subsidiary to the informative ubiquitin ligase activity; not a standalone core function.
human	RNF41	IPR013010	GO:0008270	zinc ion binding	ACCEPT	no		Structurally required; the RING and SIAH-type zinc fingers coordinate zinc, essential for the RING fold and catalytic activity.
human	RNF5	IPR045103	GO:0005783	endoplasmic reticulum	ACCEPT	no		Correct compartment; redundant with the more specific ER membrane annotations and IDA (HPA) evidence.
human	RNF5	IPR045103	GO:0006511	ubiquitin-dependent protein catabolic process	ACCEPT	no		Correct but generic; the specific GO:0036503 (ERAD pathway) better captures the core biological role.
human	ROR1	IPR001245,IPR008266	GO:0004672	protein kinase activity	REMOVE	yes		Electronic over-propagation contradicted by the curated NOTs and the CAUTION (degenerate kinase, no ATP binding). Remove.
human	RPL18A	IPR021138,IPR023573	GO:0006412	translation	ACCEPT	no		Correct general annotation capturing the biological process in which the ribosome functions.
human	RPS3	IPR001351,IPR005703	GO:0006412	translation	ACCEPT	no		Translation is the principal biological process associated with RPS3's structural ribosome function.
human	RPS3	IPR005703	GO:0015935	small ribosomal subunit	ACCEPT	no		This cellular component matches the core ribosomal role of RPS3.
human	RUNX3	IPR008967,IPR012346,IPR013524	GO:0003700	DNA-binding transcription factor activity	MODIFY	yes	GO:0000981 DNA-binding transcription factor activity, RNA polymerase II-specific	RUNX3 functions as a sequence-specific RNA polymerase II transcription factor, so the more specific term is preferred.
human	RUNX3	IPR000040	GO:0005524	ATP binding	REMOVE	yes		RUNX3 is a non-enzymatic DNA-binding transcription factor; ATP-dependent chromatin-remodeling context should not be transferred to RUNX3 as ATP binding.
human	RUNX3	IPR000040,IPR008967,IPR012346,IPR013524	GO:0006355	regulation of DNA-templated transcription	MODIFY	yes	GO:0006357 regulation of transcription by RNA polymerase II	RUNX3 target-gene regulation is best represented by regulation of transcription by RNA polymerase II.
human	SAMD8	IPR045221	GO:0016780	phosphotransferase activity, for other substituted phosphate groups	ACCEPT	no		This annotation correctly captures SAMD8 phosphotransferase activity for substituted phosphate groups (phosphoethanolamine). This is more specific than general transferase activity and appropriate for the enzyme function.
human	SAMM50	IPR000184	GO:0019867	outer membrane	MODIFY	yes	GO:0005741 mitochondrial outer membrane	The taxon/gene-specific evidence supports mitochondrial outer membrane as the precise location.
human	SCAMP1	IPR007273	GO:0016020	membrane	ACCEPT	no		The annotation is correct; SCAMP1 is a multi-pass membrane protein. More specific membrane localizations (TGN membrane, recycling endosome membrane) are also annotated.
human	SCAMP2	IPR007273	GO:0016020	membrane	ACCEPT	no		Membrane localization is fundamental to SCAMP2 function. It is a tetraspanning integral membrane protein. This annotation is correct but very broad - more specific membrane annotations (TGN membrane, recycling endosome membrane) also exist.
human	SCAMP5	IPR007273	GO:0016020	membrane	ACCEPT	no		The annotation is correct but very general. SCAMP5 has four predicted transmembrane domains and localizes to multiple membrane compartments.
human	SCG5	IPR007945	GO:0030141	secretory granule	ACCEPT	no		Localization of SCG5/7B2 to secretory granules is well established and is consistent with its known biology as a neuroendocrine secretory pathway protein.
human	SCGB1A1	IPR000329	GO:0007165	signal transduction	MODIFY	yes	GO:0050728 negative regulation of inflammatory response; GO:0009968 negative regulation of signal transduction	"While SCGB1A1 impacts multiple signaling pathways (NF-κB, prostaglandin signaling, inflammatory cytokine signaling), it does so through indirect mechanisms: inhibiting phospholipase A2, sequestering inflammatory mediators, and modulating immune cell function. The term ""signal transduction"" implies SCGB1A1 acts as a signaling molecule itself, which is not accurate. More appropriate terms would be ""negative regulation of inflammatory response"" or ""negative regulation of signal transduction"" to capture its inhibitory effects on inflammatory signaling cascades."
human	SCN1A	IPR001696,IPR008051,IPR010526	GO:0001518	voltage-gated sodium channel complex	ACCEPT	no		Duplicate of earlier IBA annotation for the same GO term. This IEA annotation provides additional computational support for SCN1A being part of voltage-gated sodium channel complex, consistent with its role as the pore-forming α-subunit.
human	SCN1A	IPR005821	GO:0005216	monoatomic ion channel activity	ACCEPT	no		This is a broader molecular function term that encompasses sodium channel activity. While accurate, it is less informative than the specific voltage-gated sodium channel activity annotation. This represents a valid but general annotation.
human	SCN1A	IPR043203	GO:0005261	monoatomic cation channel activity	ACCEPT	no		This is a broader molecular function term that encompasses sodium channel activity. Sodium channels are indeed monoatomic cation channels, but this annotation is less specific than voltage-gated sodium channel activity. Still accurate but general.
human	SCN1A	IPR005821	GO:0055085	transmembrane transport	MARK_AS_OVER_ANNOTATED	yes		This is a broad biological process term that encompasses the specific sodium ion transmembrane transport function. While accurate, it provides less informative value than more specific transport annotations.
human	SCN9A	IPR001696,IPR010526	GO:0001518	voltage-gated sodium channel complex	ACCEPT	no		Correct component, consistent with the experimentally and phylogenetically supported annotations to the identical term.
human	SCN9A	IPR005821	GO:0005216	monoatomic ion channel activity	KEEP_AS_NON_CORE	yes		Correct but uninformatively general; superseded by the specific MF term.
human	SCN9A	IPR043203	GO:0005261	monoatomic cation channel activity	KEEP_AS_NON_CORE	yes		Correct but uninformatively general; superseded by the specific Na+ channel MF term.
human	SCN9A	IPR005821	GO:0006811	monoatomic ion transport	KEEP_AS_NON_CORE	yes		Correct but uninformatively general; superseded by the specific Na+ transport terms.
human	SCN9A	IPR001696,IPR010526	GO:0006814	sodium ion transport	KEEP_AS_NON_CORE	yes		Correct but a less specific sibling/parent of the IBA-annotated sodium ion transmembrane transport term.
human	SCN9A	IPR005821	GO:0016020	membrane	KEEP_AS_NON_CORE	yes		Correct but uninformatively general; superseded by plasma membrane.
human	SCN9A	IPR005821	GO:0055085	transmembrane transport	KEEP_AS_NON_CORE	yes		Correct but uninformatively general; superseded by the specific Na+ transmembrane transport term.
human	SCO1	IPR017276	GO:0005507	copper ion binding	ACCEPT	no		Core biochemical property supporting copper chaperone activity. The existing annotation is IEA, but patient-cell and pathway-ordering evidence support the functional importance of the CxxxC copper-coordinating motif in SCO1-dependent COX2 maturation.
human	SCO1	IPR017276	GO:0006878	intracellular copper ion homeostasis	KEEP_AS_NON_CORE	yes		Keep as a valid secondary function, not the core annotation. Falcon-summarized 2023-2024 work in hepatocyte-specific Sco1 loss models links SCO1 deficiency to hepatic copper deficiency, elevated circulating copper/ceruloplasmin, and copper-dependent immunosuppression signaling, supporting a real but secondary role in systemic copper homeostasis.
human	SCO1	IPR017276	GO:0008535	respiratory chain complex IV assembly	ACCEPT	no		Correct biological-process annotation.
human	SCO1	IPR017276	GO:0016531	copper chaperone activity	ACCEPT	no		Core molecular function. OpenScientist review of the focused core-function hypothesis judged this term supported, while highlighting that the current GOA term is IEA-only and should be upgraded or complemented with experimental support from patient-cell studies and pathway-ordering work.
human	SCO2	IPR017276	GO:0005507	copper ion binding	ACCEPT	no		Copper ion binding is a core molecular function of SCO2. The structural data from PMID:17850752 directly demonstrates copper coordination by the CXXXC motif (C133 and C137) and H224. The IEA annotation from InterPro is consistent with experimental evidence and is at the correct level of specificity.
human	SCO2	IPR017276	GO:0006878	intracellular copper ion homeostasis	KEEP_AS_NON_CORE	yes		While SCO2 does participate in copper handling, its primary role is copper delivery to COX2 in the context of CIV assembly, not broad intracellular copper homeostasis. The copper homeostasis function described in PMID:17189203 represents a regulatory or secondary effect rather than the core evolved function of SCO2. Keeping as non-core rather than removing because there is published evidence for a regulatory role in copper homeostasis.
human	SCO2	IPR017276	GO:0008535	respiratory chain complex IV assembly	ACCEPT	no		This is the parent term of GO:0033617 which is already annotated with stronger evidence. While slightly less specific than the mitochondrial-specific child term, it is not incorrect for an IEA annotation and is subsumed by the more specific annotation.
human	SCO2	IPR017276	GO:0016531	copper chaperone activity	ACCEPT	no		Copper chaperone activity is the primary molecular function of SCO2. It directly binds copper and delivers it to the CuA site of COX2. This is strongly supported by structural (PMID:17850752), genetic (PMID:10545952, PMID:15229189), and biochemical (PMID:19336478, PMID:25959673) evidence.
human	SDHA	IPR011281,IPR014006	GO:0016627	oxidoreductase activity, acting on the CH-CH group of donors	ACCEPT	no		Correct classification. Succinate oxidation to fumarate involves removal of two hydrogens from the CH2-CH2 group to form the trans double bond of fumarate. This InterPro-based IEA is accurate.
human	SDHA	IPR014006	GO:0022900	electron transport chain	ACCEPT	no		Correct but more general than the IBA annotation GO:0006121. Complex II is part of the electron transport chain. Acceptable for IEA to use the broader term.
human	SDHA	IPR011281,IPR014006	GO:0050660	flavin adenine dinucleotide binding	ACCEPT	no		Correct and consistent with the IBA annotation. FAD is covalently bound to SDHA at His99.
human	SDHB	IPR025192	GO:0009055	electron transfer activity	ACCEPT	no		Electron transfer activity is the core subunit-specific molecular function of SDHB. Its three iron-sulfur clusters ([2Fe-2S], [4Fe-4S], [3Fe-4S]) form the electron relay pathway in Complex II. This is well-established from structural and biochemical data.
human	SDHC	IPR014314,IPR018495	GO:0009055	electron transfer activity	MODIFY	yes	GO:0009055 electron transfer activity	SDHC contributes to electron transfer as part of Complex II via heme b and the Q-site, but it does not independently enable electron transfer activity. The InterPro-based annotation is reasonable but the qualifier should be 'contributes_to'. Additionally, a more specific term would be preferred if available. Accept the annotation concept but flag that the qualifier in GOA is 'enables' whereas 'contributes_to' would be more appropriate for a membrane anchor subunit.
human	SDHC	IPR018495,IPR034804	GO:0016020	membrane	ACCEPT	no		Correct but general. SDHC is an integral membrane protein with three transmembrane helices. It is acceptable for IEA annotations to be broader than experimental annotations. The more specific GO:0005743 is also present.
human	SDHD	IPR007992	GO:0005740	mitochondrial envelope	ACCEPT	no		Correct localization. SDHD is embedded in the inner mitochondrial membrane, which is part of the mitochondrial envelope. The more specific GO:0005743 is also present from IDA, NAS, TAS, ISS, and IEA evidence. Acceptable for an IEA to be at this broader level.
human	SDHD	IPR007992,IPR034804	GO:0016020	membrane	ACCEPT	no		Correct but very general. Acceptable for an IEA to be at this broad level. The more specific GO:0005743 (mitochondrial inner membrane) is also annotated.
human	SEC11A	IPR001733	GO:0008233	peptidase activity	ACCEPT	no		Correct general molecular function; GO:0004252 is the informative specific term.
human	SEC11A	IPR001733,IPR019756,IPR019758	GO:0016020	membrane	KEEP_AS_NON_CORE	yes		Correct but generic; ER membrane (GO:0005789) is the specific and informative localization.
human	SEC11C	IPR001733	GO:0008233	peptidase activity	ACCEPT	no		Correct general molecular function; GO:0004252 is the informative specific term.
human	SEC11C	IPR001733,IPR019756,IPR019758	GO:0016020	membrane	KEEP_AS_NON_CORE	yes		Correct but generic; ER membrane (GO:0005789) is the specific and informative localization.
human	SEC62	IPR004728	GO:0015031	protein transport	ACCEPT	no		Correct general biological process; the specific GO:0031204 better captures SEC62's translocation role.
human	SERP1	IPR010580	GO:0005783	endoplasmic reticulum	ACCEPT	no		Correct core localization.
human	SERP2	IPR010580	GO:0005783	endoplasmic reticulum	ACCEPT	no		Correct core localization.
human	SERPINH1	IPR000215,IPR033830	GO:0004867	serine-type endopeptidase inhibitor activity	MARK_AS_OVER_ANNOTATED	yes		Domain-based transfer; HSP47/SERPINH1 does not function as a serine protease inhibitor despite its serpin fold.
human	SERPINH1	IPR033830	GO:0005518	collagen binding	ACCEPT	no		Directly supported by UniProt FUNCTION and by extensive literature; collagen binding is the central molecular activity of HSP47.
human	SFT2D3	IPR007305,IPR011691	GO:0016192	vesicle-mediated transport	ACCEPT	no		The Got1/Sft2 InterPro domain (IPR007305) is specifically associated with vesicle transport function. Multiple experimental studies in yeast and functional studies of mammalian paralogs support this core function.
human	SGCA	IPR015919	GO:0005509	calcium ion binding	ACCEPT	no		Multiple lines of evidence support calcium binding capability. The deep research describes calcium-binding pockets in the cadherin-like domain and the ATP-hydrolysing activity requiring both Ca2+ and Mg2+. UniProt features include predicted calcium-binding regions. While this is IEA, the inference is well-supported by structural and biochemical data.
human	SGCA	IPR006644,IPR015919	GO:0016020	membrane	MODIFY	yes	GO:0005886 plasma membrane; GO:0042383 sarcolemma	The term membrane is overly broad and does not capture the specific sarcolemmal/plasma membrane localization of SGCA. More specific terms like plasma membrane, sarcolemma, or cell membrane are available and provide more biological information about where the protein actually functions. Generic membrane annotations should be replaced with more specific cellular component terms.
human	SGCE	IPR006644	GO:0016020	membrane	ACCEPT	no		Accurate but very general cellular component term. SGCE is definitively a membrane protein. More specific terms like plasma membrane, sarcolemma, and synaptic membranes capture functional sites, but this general term is not incorrect.
human	SIAH1	IPR013010	GO:0008270	zinc ion binding	ACCEPT	no		Structurally required; the RING and SIAH-type zinc fingers coordinate zinc, essential for the fold and catalysis.
human	SIRT1	IPR003000	GO:0070403	NAD+ binding	ACCEPT	no		Core molecular function. NAD+ binding is essential for SIRT1 catalytic activity.
human	SIRT2	IPR017328	GO:0017136	histone deacetylase activity, NAD-dependent	ACCEPT	no		Fundamental enzymatic activity confirmed by structural and biochemical studies.
human	SIRT2	IPR017328	GO:0051287	NAD binding	ACCEPT	no		Confirmed by crystal structure showing NAD-binding Rossmann fold domain.
human	SIRT2	IPR003000	GO:0070403	NAD+ binding	ACCEPT	no		Core requirement for SIRT2 enzymatic activity confirmed structurally.
human	SLC14A1	IPR004937	GO:0016020	membrane	ACCEPT	no		While this is a very general term, it is not incorrect. SLC14A1 is indeed an integral membrane protein. The more specific plasma membrane annotations are also present, so this broader annotation provides general context from InterPro domain analysis.
human	SLC14A1	IPR004937	GO:0071918	urea transmembrane transport	ACCEPT	no		The InterPro-derived annotation is correct and consistent with the IBA annotation and direct experimental evidence. Duplicates with different evidence codes are acceptable and provide independent support.
human	SLC3A2	IPR006047	GO:0005975	carbohydrate metabolic process	REMOVE	yes		SLC3A2 does not participate in carbohydrate metabolism. While it contains an alpha-amylase-like domain fold, this domain has been repurposed for structural roles in membrane association and heterodimer formation, not carbohydrate hydrolysis. Recent structural studies (PMID:30867591, PMID:33298890) confirm this domain mediates protein-protein interactions, not enzymatic activity.
human	SLC40A1	IPR009716	GO:0016020	membrane	ACCEPT	no		Ferroportin is an integral membrane protein with 12 transmembrane helices. While this is a broad annotation, it is accurate. More specific plasma membrane and basolateral membrane annotations are also present.
human	SLC40A1	IPR009716	GO:0034755	iron ion transmembrane transport	ACCEPT	no		This annotation is consistent with ferroportin's well-established function and is supported by IBA and IMP evidence for the same term.
human	SLC7A11	IPR002293	GO:0022857	transmembrane transporter activity	MARK_AS_OVER_ANNOTATED	yes		Too general. GO:0015327 (cystine:glutamate antiporter activity) is the appropriate specific molecular function.
human	SLC7A11	IPR002293	GO:0055085	transmembrane transport	MARK_AS_OVER_ANNOTATED	yes		Too general. Specific transport processes are well-annotated.
human	SOCS4	IPR037342	GO:0032436	positive regulation of proteasomal ubiquitin-dependent protein catabolic process	ACCEPT	no		This annotation accurately captures SOCS4's core molecular mechanism. The crystal structure of SOCS4-Elongin B/C complex (PMID:17997974) demonstrates how SOCS box recruits ubiquitination machinery. Deep research confirms SOCS4 promotes EGFR degradation through this mechanism. This is a fundamental aspect of SOCS4 function and merits acceptance despite IEA evidence code.
human	SOCS4	IPR036036	GO:0035556	intracellular signal transduction	MARK_AS_OVER_ANNOTATED	yes		This annotation is at the wrong level of granularity. SOCS4's role is specifically as a SOCS-box adaptor that attenuates activated EGFR and related cytokine/growth-factor signaling through receptor binding and ubiquitin-dependent degradation. The existing reviewed annotations already capture that biology without adding the unsupported ERBB2-specific pathway.
human	SOCS5	IPR037343	GO:0007259	cell surface receptor signaling pathway via JAK-STAT	ACCEPT	no		"SOCS proteins are classical negative regulators of JAK-STAT signaling pathways. PMID:10773671 describes SOCS5 (CIS6) as structurally related to other CIS family members that act as negative regulators of JAK signaling. The protein is named ""Suppressor of cytokine signaling"" precisely because it inhibits this pathway. This annotation accurately captures core function."
human	SOCS5	IPR037343	GO:0032436	positive regulation of proteasomal ubiquitin-dependent protein catabolic process	ACCEPT	no		This annotation accurately captures the mechanism by which SOCS5 exerts its regulatory effects. SOCS5 contains a SOCS box domain that mediates interaction with Elongin BC complex, an adapter in E3 ubiquitin ligase complexes. PMID:15590694 demonstrates that SOCS5 promotes EGFR ubiquitination and degradation via this mechanism. This is a fundamental aspect of SOCS5 function.
human	SOCS5	IPR036036	GO:0035556	intracellular signal transduction	MARK_AS_OVER_ANNOTATED	yes		"This term is overly general and does not add informative value beyond the more specific annotations already present. SOCS5 is involved in intracellular signal transduction, but this is better captured by specific terms like ""cytokine-mediated signaling pathway"", ""JAK-STAT pathway"", and ""EGFR signaling pathway"" that describe the actual pathways regulated. This represents annotation to a high-level parent term that is not informative."
human	SOD1	IPR001424,IPR036423	GO:0046872	metal ion binding	KEEP_AS_NON_CORE	yes		Correct but less informative than the specific copper (GO:0005507) and zinc (GO:0008270) ion binding annotations; retained as a broader parent.
human	SOX2	IPR022097	GO:0006355	regulation of DNA-templated transcription	ACCEPT	no		This is a valid high-level annotation based on domain architecture. All SOX family transcription factors regulate transcription, and this annotation is appropriately general. While less specific than the positive/negative regulation terms, it is not incorrect.
human	SPARC	IPR019577	GO:0005509	calcium ion binding	ACCEPT	no		This IEA annotation based on InterPro domain recognition is consistent with the experimentally validated calcium binding function and can be retained as supporting evidence.
human	SPARC	IPR001999	GO:0005615	extracellular space	ACCEPT	no		This IEA annotation from InterPro is consistent with experimental evidence and can be retained.
human	SPCS1	IPR009542	GO:0005787	signal peptidase complex	ACCEPT	no		Correct core complex membership; redundant with experimental IPI/IBA evidence.
human	SPCS1	IPR009542	GO:0016020	membrane	KEEP_AS_NON_CORE	yes		Correct but uninformative; the specific GO:0005789 (ER membrane) better captures SPCS1 localization.
human	SPCS2	IPR009582	GO:0005787	signal peptidase complex	ACCEPT	no		Correct core complex membership; redundant with experimental IPI/IBA evidence.
human	SPCS2	IPR009582	GO:0016020	membrane	KEEP_AS_NON_CORE	yes		Correct but uninformative; the specific GO:0005789 (ER membrane) better captures SPCS2 localization.
human	SPCS3	IPR007653	GO:0005787	signal peptidase complex	ACCEPT	no		Correct core complex membership; redundant with experimental IPI/IBA evidence.
human	SPCS3	IPR007653	GO:0016020	membrane	KEEP_AS_NON_CORE	yes		Correct but uninformative; the specific GO:0005789 (ER membrane) better captures SPCS3 localization.
human	SPDL1	IPR028593	GO:0007094	mitotic spindle assembly checkpoint signaling	ACCEPT	no		IEA annotation for SAC signaling based on InterPro domain mapping (IPR028593). The role of Spindly in SAC signaling is complex. In Drosophila, Spindly depletion prevents SAC silencing (PMID:17576797). In human cells, hSpindly depletion does NOT abolish removal of checkpoint proteins MAD2 and ZW10 from kinetochores (PMID:19468067), but Spindly mutants that cannot recruit dynein DO prevent checkpoint silencing (PMID:20439434). Thus Spindly is involved in SAC signaling primarily through its role in checkpoint silencing via dynein-mediated removal of checkpoint components. Falcon deep research updates this model with Ide et al. 2023: the checkpoint-silencing role of Spindly-recruited dynein is restricted primarily to disassembly of the fibrous corona, rather than wholesale removal of all checkpoint proteins from the outer kinetochore.
human	SPNS1	IPR011701,IPR020846	GO:0022857	transmembrane transporter activity	ACCEPT	no		Retain the broad transporter term rather than replacing it with GO:0051978, whose sodium-coupled label does not match the proton-gradient-dependent SPNS1 evidence. A proton-specific lysophospholipid symporter term is requested below.
human	SPNS1	IPR011701	GO:0055085	transmembrane transport	MODIFY	yes	GO:0051977 lysophospholipid transport	Replace the broad transmembrane transport term with the specific lysophospholipid transport process.
human	SPOCK1	IPR019577	GO:0005509	calcium ion binding	ACCEPT	no		This IEA annotation is based on the presence of the SPARC/Testican calcium-binding domain (InterPro IPR019577) and is consistent with experimental evidence. While duplicate, it provides computational confirmation of the calcium-binding function.
human	SPOCK2	IPR019577	GO:0005509	calcium ion binding	ACCEPT	no		While duplicate, this IEA annotation from InterPro domain analysis provides additional independent evidence for calcium binding function. It is acceptable to have multiple evidence codes supporting the same well-established function.
human	SPOCK3	IPR019577	GO:0005509	calcium ion binding	ACCEPT	no		This is a duplicate GO ID annotation but from a different evidence pipeline (IEA from InterPro vs IBA from phylogenetic inference). Both are correct. The IEA annotation is based on the presence of InterPro domain IPR019577 (SPARC/Testican_Ca-bd-dom), which maps to calcium ion binding function. Having multiple evidence codes for the same function from independent sources (domain-based inference and phylogenetic inference) strengthens confidence in the annotation. This is standard practice in GO annotation - duplicates with different evidence codes are acceptable and informative.
human	SPR	IPR006393	GO:0006729	tetrahydrobiopterin biosynthetic process	ACCEPT	no		This IEA is accurate and consistent with the experimentally supported IBA annotation. The InterPro domain is specific to sepiapterin reductase family members that function in BH4 biosynthesis.
human	SQSTM1	IPR000433	GO:0008270	zinc ion binding	KEEP_AS_NON_CORE	yes		Correct structural metal-binding activity of the ZZ domain, but ancillary to the core ubiquitin-reader/adaptor function rather than a standalone core MF.
human	SRP19	IPR002778,IPR036521	GO:0006614	SRP-dependent cotranslational protein targeting to membrane	ACCEPT	no		Correct core process; redundant with IBA/TAS evidence.
human	SRP19	IPR002778,IPR036521	GO:0008312	7S RNA binding	ACCEPT	no		Correct core molecular function; redundant with IDA evidence.
human	SRP19	IPR002778,IPR036521	GO:0048500	signal recognition particle	ACCEPT	no		Core cellular component; redundant with the more specific GO:0005786.
human	SRP68	IPR034652,IPR038253	GO:0003723	RNA binding	ACCEPT	no		Correct general molecular function; the more precise GO:0008312 (7S RNA binding) better captures the specific activity.
human	SRP68	IPR026258	GO:0005047	signal recognition particle binding	ACCEPT	no		Correct core molecular function; redundant with IBA and IPI evidence.
human	SRP68	IPR026258	GO:0005786	signal recognition particle, endoplasmic reticulum targeting	ACCEPT	no		Correct core cellular component; redundant with IBA/IDA.
human	SRP68	IPR026258	GO:0006614	SRP-dependent cotranslational protein targeting to membrane	ACCEPT	no		Correct core biological process; redundant with experimentally supported annotations.
human	SRP68	IPR026258	GO:0008312	7S RNA binding	ACCEPT	no		Core molecular function with structural support (crystal structures of SRP68-RBD with SRP RNA); also supported by IMP.
human	SRP68	IPR026258	GO:0030942	endoplasmic reticulum signal sequence receptor activity	MARK_AS_OVER_ANNOTATED	yes		SRP68 is an RNA-binding scaffold subunit of the cytosolic SRP, not a membrane signal-sequence receptor; signal-sequence receptor activity belongs to the SRP receptor (SRPR/SRPRB) and the SSR/TRAP complex, not to SRP68.
human	SRP72	IPR013699,IPR026270	GO:0006614	SRP-dependent cotranslational protein targeting to membrane	ACCEPT	no		Correct core biological process; redundant with IBA annotation.
human	SRP72	IPR013699	GO:0008312	7S RNA binding	ACCEPT	no		Correct core molecular function; redundant with IMP/IBA.
human	SRP72	IPR013699	GO:0048500	signal recognition particle	ACCEPT	no		Correct core cellular component; SRP72 is a defining SRP subunit.
human	SRP9	IPR008832,IPR009018,IPR039914	GO:0006614	SRP-dependent cotranslational protein targeting to membrane	ACCEPT	no		Correct core process; redundant with IBA/NAS evidence.
human	SRP9	IPR008832,IPR009018	GO:0008312	7S RNA binding	ACCEPT	no		Core molecular function; SRP9 (with SRP14) binds the Alu portion of the SRP RNA.
human	SRP9	IPR008832	GO:0045900	negative regulation of translational elongation	ACCEPT	no		Core biological process; SRP9 is part of the Alu/elongation-arrest domain that negatively regulates elongation.
human	SRP9	IPR008832,IPR009018,IPR039914	GO:0048500	signal recognition particle	ACCEPT	no		Core cellular component; redundant with the more specific GO:0005786.
human	SRPRB	IPR024156	GO:0005525	GTP binding	ACCEPT	no		Core molecular function; SRPRB binds GTP (structure solved in the Mg2+-GTP-bound state) and its GTPase activity regulates targeting.
human	SSR2	IPR008856	GO:0005783	endoplasmic reticulum	ACCEPT	no		Accurate annotation. SSR2 is an integral ER membrane protein as part of the TRAP complex. The InterPro-based inference is consistent with extensive experimental evidence showing ER localization [PMID:7789174, PMID:36697828].
human	SSR2	IPR008856	GO:0016020	membrane	MARK_AS_OVER_ANNOTATED	yes		GO:0005789 (endoplasmic reticulum membrane) is already annotated and is strictly more specific. GO:0016020 is redundant given that more precise localization information is captured by the ER-membrane term; best-practice curation flags such general terms as over-annotations when a specific child is present.
human	STAT1	IPR001217,IPR008967,IPR022752	GO:0003700	DNA-binding transcription factor activity	ACCEPT	no		While GO:0000981 is more specific and preferred, this broader term still accurately describes STAT1's transcriptional function. Both terms can coexist as they represent different levels of annotation granularity, with the specific term providing more mechanistic detail.
human	STAT1	IPR001217,IPR008967,IPR013799,IPR013800,IPR015988	GO:0006355	regulation of DNA-templated transcription	ACCEPT	no		A correct but general transcription-regulation term; acceptable as a broad parent of STAT1's specific transcriptional roles.
human	STAT1	IPR001217,IPR013799,IPR013800,IPR015988	GO:0007165	signal transduction	ACCEPT	no		Generic signal transduction is a true parent of STAT1's JAK-STAT signaling role; acceptable though more specific terms are preferred.
human	STAT3	IPR001217,IPR008967,IPR013799,IPR013800,IPR015988	GO:0006355	regulation of DNA-templated transcription	ACCEPT	no		Core biological process - JAK-STAT signaling and transcriptional regulation
human	STAT3	IPR001217,IPR013799,IPR013800,IPR015988	GO:0007165	signal transduction	KEEP_AS_NON_CORE	yes		Valid annotation but peripheral to core STAT3 transcription factor function
human	STAT4	IPR001217,IPR008967,IPR013799,IPR013800,IPR015988	GO:0006355	regulation of DNA-templated transcription	ACCEPT	no		Correct but general. The IEA from InterPro captures the transcription regulation function of STAT4. The more specific term GO:0006357 is annotated via IBA. This broader IEA annotation is acceptable.
human	STAT4	IPR001217,IPR013799,IPR013800,IPR015988	GO:0007165	signal transduction	ACCEPT	no		"Correct but very general. STAT4 is literally named ""Signal Transducer and Activator of Transcription 4."" The more specific term GO:0007259 (JAK-STAT pathway) is annotated via IBA and other evidence types. This broad IEA is acceptable."
human	STOM	IPR001972	GO:0016020	membrane	KEEP_AS_NON_CORE	yes		While correct (stomatin is a membrane protein), this generic term is subsumed by the more specific plasma membrane annotations. It provides minimal additional information.
human	STOML3	IPR001972	GO:0016020	membrane	ACCEPT	no		Accurate general localization consistent with the stomatin domain architecture.
human	STUB1	IPR003613	GO:0004842	ubiquitin-protein transferase activity	ACCEPT	no		Directly supported by UniProt FUNCTION; CHIP is a well-characterized U-box E3 ligase that ubiquitinates chaperone clients for degradation.
human	STX12	IPR006012	GO:0005484	SNAP receptor activity	ACCEPT	no		STX12 is a syntaxin SNARE that promotes endosomal vesicle movement, docking, and fusion with target membranes.
human	STX12	IPR006012	GO:0006886	intracellular protein transport	ACCEPT	no		STX12 is a syntaxin SNARE that promotes endosomal vesicle movement, docking, and fusion with target membranes.
human	STX12	IPR010989	GO:0016192	vesicle-mediated transport	ACCEPT	no		STX12 is a syntaxin SNARE that promotes endosomal vesicle movement, docking, and fusion with target membranes.
human	SURF1	IPR002994	GO:0016020	membrane	ACCEPT	no		While very general, this IEA annotation from InterPro is technically correct. SURF1 contains transmembrane domains and is an integral membrane protein. More specific mitochondrial inner membrane annotations are present from other evidence codes. It is acceptable for an IEA to be broader than what is established by more detailed evidence.
human	SYN1	IPR013815	GO:0005524	ATP binding	ACCEPT	no		ATP binding is supported by the domain architecture of synapsin-1. The protein has a well-characterized ATP-binding domain (domain C) with ATP-grasp fold structure. Deep research explicitly states domain C binds ATP/ADP. This IEA from InterPro mapping is accurate.
human	SYN1	IPR001359	GO:0007269	neurotransmitter secretion	ACCEPT	no		Neurotransmitter secretion is a core process that SYN1 regulates. The protein's function in SV clustering and reserve pool maintenance directly controls neurotransmitter release. This is well-supported by multiple publications.
human	SYN2	IPR013815	GO:0005524	ATP binding	ACCEPT	no		Valid IEA annotation based on domain content. The ATP-grasp domain is present in SYN2 and ATP binding is functionally relevant - ATP modulates the balance between LLPS and oligomerization states.
human	SYN2	IPR001359	GO:0007269	neurotransmitter secretion	ACCEPT	no		Valid annotation supported by domain inference and literature. SYN2 indirectly regulates neurotransmitter secretion by controlling vesicle pool organization and mobilization.
human	SYN2	IPR001359	GO:0008021	synaptic vesicle	ACCEPT	no		Valid localization annotation. SYN2 is physically associated with synaptic vesicles as a peripheral membrane protein.
human	SYN3	IPR001359	GO:0007269	neurotransmitter secretion	ACCEPT	no		This is a core function of the synapsin family. Synapsins regulate the transition of vesicles between reserve and readily releasable pools, thereby modulating neurotransmitter release. The IEA annotation is consistent with literature evidence.
human	SYNGAP1	IPR037779	GO:0046580	negative regulation of Ras protein signal transduction	ACCEPT	no		This annotation correctly captures SynGAP's inhibitory role in Ras signaling. By functioning as a RasGAP, SynGAP terminates Ras signaling and thereby limits downstream ERK/MAPK activation and AMPA receptor insertion at synapses.
human	TANK	IPR039669	GO:0043124	negative regulation of canonical NF-kappaB signal transduction	KEEP_AS_NON_CORE	yes		Correct and supported by experimental evidence, but reflects the secondary genotoxic/IL-1 NF-kappaB-restraining role rather than TANK's core TBK1/IKK adaptor function; redundant with the IMP annotation.
human	TARDBP	IPR035979	GO:0003676	nucleic acid binding	ACCEPT	no		The IEA annotation from InterPro is correct as TDP-43 binds both RNA (UG-rich) and DNA (TG-rich). However, this is subsumed by more specific annotations for RNA binding and DNA binding. Acceptable to keep as it captures the broader function.
human	TBK1	IPR000719	GO:0004672	protein kinase activity	ACCEPT	no		Core molecular function directly demonstrated by multiple experimental studies.
human	TBK1	IPR000719,IPR017441	GO:0005524	ATP binding	ACCEPT	no		Correct and integral to the core protein kinase activity.
human	TERT	IPR003545	GO:0000723	telomere maintenance	MARK_AS_OVER_ANNOTATED	yes		More specific child term GO:0007004 (telomere maintenance via telomerase) is annotated
human	THBS1	IPR001881,IPR003367,IPR008859,IPR028974	GO:0005509	calcium ion binding	ACCEPT	no		Calcium binding is a well-documented property of TSP1. The type 3 repeat region contains multiple calcium-binding loops that are critical for protein structure and function. This is supported by structural studies and InterPro domain analysis.
human	THBS2	IPR001881,IPR003367,IPR008859,IPR028974	GO:0005509	calcium ion binding	ACCEPT	no		Calcium binding is a structural feature of the type III repeats, confirmed by crystal structure (PDB 1YO8).
human	THBS2	IPR008859	GO:0005576	extracellular region	ACCEPT	no		Core localization for this secreted matricellular protein.
human	THBS3	IPR001881,IPR003367,IPR008859,IPR018097,IPR028974	GO:0005509	calcium ion binding	ACCEPT	no		UniProt documents multiple EGF-like calcium-binding domains and type 3 repeats that bind calcium [UniProt P49746]. The deep research indicates thrombospondins bind 10-12 calcium ions per subunit with moderate affinity (Kd ~0.1 mM) [PMID:7558000]. Calcium binding is essential for proper protein structure and function.
human	THBS3	IPR008859,IPR028507	GO:0005576	extracellular region	ACCEPT	no		UniProt confirms a signal peptide (residues 1-22) directing THBS3 to the secretory pathway [UniProt P49746]. The protein is found in the extracellular medium [PMID:8288588] and functions as a matricellular protein in the ECM. This broader term encompasses the more specific ECM localization.
human	THBS4	IPR001881,IPR003367,IPR008859,IPR018097,IPR028974	GO:0005509	calcium ion binding	ACCEPT	no		Calcium binding is a well-established property of TSP-4, supported by IDA evidence (PMID:7852353, PMID:16246837) as well as domain architecture containing calcium-binding EGF-like modules. The IEA annotation is correct and consistent with experimental evidence.
human	TIA1	IPR003954,IPR035979	GO:0003676	nucleic acid binding	MODIFY	yes	GO:0003723 RNA binding	While technically correct (TIA1 does bind nucleic acids including RNA and has been shown to bind DNA in COL2A1 genomic DNA), this term is too broad and uninformative. The more specific 'RNA binding' (GO:0003723) better represents TIA1's primary molecular function, which is extensively characterized for RNA. Note that TIA1 can also bind DNA but this appears to be a minor function.
human	TIMM17A	IPR005678	GO:0005744	TIM23 mitochondrial import inner membrane translocase complex	ACCEPT	no		Correct InterPro-derived annotation. TIMM17A belongs to the Tim17/Tim23 family and is part of the TIM23 inner membrane translocase.
human	TIMM17A	IPR005678	GO:0008320	protein transmembrane transporter activity	ACCEPT	no		Correct when interpreted as a TIM23 subunit contribution to the protein-conducting channel/cavity.
human	TIMM17A	IPR005678	GO:0030150	protein import into mitochondrial matrix	ACCEPT	no		Correct InterPro-derived process annotation for the TIM23 presequence pathway. TIMM17A contributes to import of matrix-destined precursors.
human	TIMM21	IPR013261	GO:0005744	TIM23 mitochondrial import inner membrane translocase complex	ACCEPT	no		Correct. TIMM21 is a TIM23-associated accessory subunit and, with ROMO1, defines the TIM23SORT state of the TIM23 presequence translocase.
human	TIMM21	IPR013261	GO:0030150	protein import into mitochondrial matrix	MARK_AS_OVER_ANNOTATED	yes		Prefer TIM23 complex membership and protein insertion into mitochondrial inner membrane for TIMM21; matrix import is primarily a TIM23MOTOR/core translocase output rather than TIMM21-specific activity.
human	TIMM22	IPR039175	GO:0042721	TIM22 mitochondrial import inner membrane insertion complex	ACCEPT	no		Correct. TIMM22 is a core component of the human TIM22 carrier translocase complex.
human	TIMM22	IPR039175	GO:0045039	protein insertion into mitochondrial inner membrane	ACCEPT	no		Correct and core. TIMM22 mediates insertion of hydrophobic multi-pass proteins into the mitochondrial inner membrane.
human	TIMM23	IPR005681	GO:0005744	TIM23 mitochondrial import inner membrane translocase complex	ACCEPT	no		Correct. TIMM23 is a core component of the TIM23 mitochondrial inner-membrane presequence translocase complex.
human	TIMM23	IPR005681	GO:0008320	protein transmembrane transporter activity	ACCEPT	no		Accepted as TIMM23 contribution to TIM23-dependent protein translocation across the mitochondrial inner membrane. TIMM23 is essential in the translocase core, even though recent structural work emphasizes Tim17-family subunits as the dominant translocation cavity.
human	TIMM23	IPR045238	GO:0022857	transmembrane transporter activity	MARK_AS_OVER_ANNOTATED	yes		Use GO:0008320 protein transmembrane transporter activity and TIM23 complex annotations rather than generic transmembrane transporter activity.
human	TIMM23	IPR005681	GO:0030150	protein import into mitochondrial matrix	ACCEPT	no		Correct and core. TIMM23-containing TIM23 translocase imports presequence-containing proteins into the mitochondrial matrix.
human	TIMM44	IPR017303	GO:0030150	protein import into mitochondrial matrix	ACCEPT	no		Correct and core. TIMM44 enables ATP-dependent TIM23/PAM-mediated import of presequence-containing proteins into the mitochondrial matrix.
human	TIMM44	IPR017303	GO:0051087	protein-folding chaperone binding	ACCEPT	no		Correct. TIMM44 recruits and positions mtHsp70 and PAM co-chaperones at the matrix side of TIM23, making chaperone binding central to its import-motor role.
human	TMEM67	IPR019170	GO:0036038	MKS complex	ACCEPT	no		MKS complex membership is a core annotation for TMEM67. It is well supported by multiple publications and is also annotated by ISS (GO_REF:0000024). The IEA via InterPro is correct.
human	TMEM67	IPR019170	GO:0060271	cilium assembly	ACCEPT	no		This IEA is correct and consistent with the IBA and IMP annotations for the same term. Cilium assembly is a core function of TMEM67.
human	TNFRSF1A	IPR020419	GO:0006693	prostaglandin metabolic process	MARK_AS_OVER_ANNOTATED	yes		The link between TNFR1 and prostaglandin metabolism is indirect and downstream. TNF/TNFR1 signaling can activate NF-kappaB, which induces COX-2 expression, leading to prostaglandin production. However, annotating TNFR1 directly to prostaglandin metabolic process overstates its involvement. TNFR1 does not catalyze or directly regulate prostaglandin synthesis. MADD (which binds TNFR1) was shown to activate ERK and phospholipase A2, providing a link to arachidonic acid release, but this is still indirect (PMID:9115275).
human	TNFRSF1A	IPR020419	GO:0006954	inflammatory response	ACCEPT	no		Redundant with IBA but correct. Inflammatory response is a core process for TNFR1.
human	TNFRSF1A	IPR000488	GO:0007165	signal transduction	ACCEPT	no		While very broad, signal transduction is not incorrect for a signaling receptor. More specific terms are annotated elsewhere. It is acceptable for IEA annotations to use broader terms.
human	TOLLIP	IPR003892	GO:0043130	ubiquitin binding	ACCEPT	no		ubiquitin binding is supported as part of TOLLIP adaptor, endosomal cargo-routing, or innate immune signaling function.
human	TOMM20	IPR002056,IPR022422	GO:0005742	mitochondrial outer membrane translocase complex	ACCEPT	no		Correct. The InterPro-based inference is fully supported by experimental data showing TOMM20 is a component of the TOM complex.
human	TOMM20	IPR022422	GO:0006605	protein targeting	ACCEPT	no		Correct but broad. The IEA mapping captures the general protein targeting role of TOMM20. More specific terms (GO:0006626, GO:0030150) are also present in the annotation set.
human	TOMM20	IPR002056,IPR022422	GO:0006886	intracellular protein transport	ACCEPT	no		Correct but broad. The IEA mapping is consistent with TOMM20 function in mitochondrial protein import. Not misleading even though more specific terms exist.
human	TOMM20	IPR002056	GO:0030150	protein import into mitochondrial matrix	ACCEPT	no		Correct. Consistent with the IBA annotation and extensive experimental evidence for TOMM20 role in matrix protein import.
human	TOMM22	IPR005683	GO:0006886	intracellular protein transport	MARK_AS_OVER_ANNOTATED	yes		Use mitochondrial protein import/localization and TOM complex terms rather than generic intracellular protein transport.
human	TOMM40	IPR037930	GO:0008320	protein transmembrane transporter activity	ACCEPT	no		Redundant with IBA annotation for the same term. InterPro-based inference is correct — TOMM40 has protein transmembrane transporter activity.
human	TOMM40	IPR037930	GO:0030150	protein import into mitochondrial matrix	KEEP_AS_NON_CORE	yes		Matrix import is one specific pathway; TOMM40 serves all import routes.
human	TOMM40	IPR027246	GO:0055085	transmembrane transport	MARK_AS_OVER_ANNOTATED	yes		Too general; subsumed by more specific annotations.
human	TOMM5	IPR029179	GO:0005742	mitochondrial outer membrane translocase complex	ACCEPT	no		Correct InterPro-derived complex annotation. TOMM5 is a small subunit of the mitochondrial TOM translocase complex.
human	TOMM6	IPR029182	GO:0005742	mitochondrial outer membrane translocase complex	ACCEPT	no		Correct complex-level annotation. TOMM6 is one of the small Tom subunits of the TOM core with TOMM40, TOMM22, TOMM5, and TOMM7.
human	TOMM7	IPR012621	GO:0005742	mitochondrial outer membrane translocase complex	ACCEPT	no		Correct InterPro-derived annotation. TOMM7 is a Tom7-family small TOM complex subunit.
human	TOMM7	IPR012621	GO:0030150	protein import into mitochondrial matrix	KEEP_AS_NON_CORE	yes		Matrix import is one route through TOM; TOMM7's core role is TOM complex regulation.
human	TOP2A	IPR013758	GO:0006259	DNA metabolic process	ACCEPT	no		This is an extremely general term from IEA (InterPro-based annotation). While correct, it provides minimal information compared to more specific terms like DNA topological change or chromosome segregation.
human	TOP2B	IPR013758	GO:0006259	DNA metabolic process	ACCEPT	no		While very general, this annotation is technically correct as TOP2B is involved in DNA metabolic processes through its topoisomerase activity. More specific annotations also present.
human	TP53	IPR011615	GO:0000976	transcription cis-regulatory region binding	ACCEPT	no		This annotation accurately represents a core molecular function of p53. Multiple lines of experimental evidence confirm p53 directly binds cis-regulatory regions to regulate transcription.
human	TP53	IPR010991,IPR036674	GO:0051262	protein tetramerization	ACCEPT	no		Core structural feature - tetramerization is essential for high-affinity DNA binding and p53 function.
human	TRAF6	IPR027139,IPR037309	GO:0005164	tumor necrosis factor receptor binding	ACCEPT	no		This is a well-established function of TRAF6. Although annotated as IEA, it represents a core adaptor function that is experimentally validated in the literature. TRAF6 directly binds cytoplasmic tails of TNF receptor superfamily members.
human	TRAF6	IPR012227	GO:0042981	regulation of apoptotic process	KEEP_AS_NON_CORE	yes		Not a core defining function of TRAF6.
human	TRAF6	IPR037309	GO:0043122	regulation of canonical NF-kappaB signal transduction	ACCEPT	no		TRAF6 is a key regulator of NF-κB activation through IKK.
human	TRAPPC1	IPR007233	GO:0016192	vesicle-mediated transport	MODIFY	yes	GO:0006888 endoplasmic reticulum to Golgi vesicle-mediated transport	Modify to the more specific ER-to-Golgi vesicle-mediated transport term.
human	TRAPPC3	IPR016721	GO:0048193	Golgi vesicle transport	KEEP_AS_NON_CORE	yes		Keep as non-core because it is broader/less precise than ER-to-Golgi vesicle-mediated transport and intra-Golgi TRAPPII context.
human	TRAPPC5	IPR016696	GO:0048193	Golgi vesicle transport	KEEP_AS_NON_CORE	yes		Keep as non-core. The core process is ER-to-Golgi/TRAPP/RAB1 transport; broader Golgi vesicle transport is a reasonable parent/context but not the most specific function.
human	TRIM13	IPR000315	GO:0008270	zinc ion binding	KEEP_AS_NON_CORE	yes		Correct (RING/B-box coordinate Zn2+) and underpins ligase activity, but generic; the informative MF is ubiquitin ligase activity.
human	TRIM16	IPR000315	GO:0008270	zinc ion binding	KEEP_AS_NON_CORE	yes		Correct (the B-box coordinates Zn2+) but generic; the informative MF relates to autophagy scaffolding/ubiquitination.
human	TRIM17	IPR000315	GO:0008270	zinc ion binding	KEEP_AS_NON_CORE	yes		Correct (RING/B-box coordinate Zn2+) and underpins ligase activity, but generic; the informative MF is ubiquitin ligase activity.
human	TRIM5	IPR000315	GO:0008270	zinc ion binding	KEEP_AS_NON_CORE	yes		Correct (RING and B-box coordinate Zn2+) and underpins ligase/multimerization, but generic; the informative MF is ubiquitin ligase activity.
human	TRIP4	IPR009349	GO:0008270	zinc ion binding	ACCEPT	no		Zinc binding by the C4-type zinc finger is a structural molecular function underlying TRIP4's interaction surface; supported by domain annotation.
human	TRIP4	IPR009349	GO:0072344	rescue of stalled cytosolic ribosome	ACCEPT	no		Agrees with multiple IDA studies; a core biological process of TRIP4.
human	TRIP4	IPR009349	GO:0180022	RQC-trigger complex	ACCEPT	no		Agrees with IDA/IBA RQT-complex annotations; core cellular component.
human	TSG101	IPR008883	GO:0015031	protein transport	MODIFY	yes	GO:0043162 ubiquitin-dependent protein catabolic process via the multivesicular body sorting pathway; GO:0036258 multivesicular body assembly	The specific TSG101 transport role is ESCRT-I sorting of ubiquitinated cargo through MVB/endolysosomal pathways, not undifferentiated protein transport.
human	TTC8	IPR028796	GO:1905515	non-motile cilium assembly	ACCEPT	no		Specific process term consistent with experimental ciliogenesis role.
human	UBA5	IPR035985	GO:0008641	ubiquitin-like modifier activating enzyme activity	MODIFY	yes	GO:0071566 UFM1 activating enzyme activity	UBA5 is specific for UFM1; the general E1 term should be replaced by the precise UFM1 activating enzyme activity (GO:0071566).
human	UBA7	IPR000011,IPR035985	GO:0008641	ubiquitin-like modifier activating enzyme activity	MODIFY	yes	GO:0019782 ISG15 activating enzyme activity	While technically correct, this annotation is too general. UBA7 specifically activates ISG15, not other ubiquitin-like modifiers. The more specific term GO:0019782 (ISG15 activating enzyme activity) better captures UBA7's molecular function.
human	UBAP1	IPR038870	GO:0000813	ESCRT I complex	ACCEPT	no		UBAP1 is an endosome-specific ESCRT-I fourth-subunit variant in TSG101-VPS28-VPS37A-UBAP1 complexes.
human	UBAP1	IPR038870	GO:0043130	ubiquitin binding	ACCEPT	no		UBAP1 binds ubiquitinated cargo through UBA/SOUBA domains and supports endosomal ubiquitin homeostasis.
human	UBAP1	IPR038870	GO:0043162	ubiquitin-dependent protein catabolic process via the multivesicular body sorting pathway	ACCEPT	no		UBAP1-containing ESCRT-I is required for sorting ubiquitinated cargo, including EGFR, into the MVB pathway.
human	UFD1	IPR004854	GO:0006511	ubiquitin-dependent protein catabolic process	ACCEPT	no		Core biological-process role.
human	UFL1	IPR018611	GO:0061666	UFM1 ligase activity	ACCEPT	no		UFL1 is the E3 ligase of the ufmylation cascade; this is its core MF.
human	UFL1	IPR018611	GO:0071569	protein ufmylation	ACCEPT	no		Core process annotation for the E3 ligase.
human	UGGT1	IPR009448	GO:0009101	glycoprotein biosynthetic process	MODIFY	yes	GO:0006487 protein N-linked glycosylation	UGGT1 does not participate in de novo glycoprotein biosynthesis. It acts downstream in the quality control cycle, reglucosylating N-glycans on misfolded glycoproteins that have already been synthesized and initially glycosylated. The IBA annotation to GO:0018279 (protein N-linked glycosylation via asparagine) is a more appropriate process term, and GO:0006487 (protein N-linked glycosylation) would also be suitable. GO:0009101 is misleading because UGGT1 does not contribute to glycoprotein biosynthesis in the usual sense.
human	UPF1	IPR018999	GO:0000184	nuclear-transcribed mRNA catabolic process, nonsense-mediated decay	ACCEPT	no		Core biological process; UPF1 is the central NMD factor.
human	UPF1	IPR006935	GO:0003677	DNA binding	KEEP_AS_NON_CORE	yes		Supported in vitro but peripheral to the core RNA/NMD function.
human	UPF1	IPR018999	GO:0003723	RNA binding	ACCEPT	no		RNA binding is well supported (including HTP mRNA-interactome and direct assays) and is integral to UPF1 function.
human	UPF1	IPR018999	GO:0003724	RNA helicase activity	ACCEPT	no		Directly and repeatedly supported; UPF1 is an RNA-dependent helicase required for NMD.
human	UPF1	IPR041677	GO:0004386	helicase activity	ACCEPT	no		Correct but less specific than RNA helicase activity; retained as a valid parent MF.
human	UPF1	IPR006935,IPR018999	GO:0005524	ATP binding	ACCEPT	no		ATP binding is integral to the SF1 helicase catalytic mechanism of UPF1.
human	UPF1	IPR018999	GO:0008270	zinc ion binding	ACCEPT	no		UPF1's N-terminal CH domain coordinates zinc and regulates helicase/UPF2 interaction.
human	UPF1	IPR006935	GO:0016787	hydrolase activity	MARK_AS_OVER_ANNOTATED	yes		Too general to be informative; the specific activities (RNA helicase, ATP hydrolysis) already capture this.
human	UPF2	IPR039762	GO:0000184	nuclear-transcribed mRNA catabolic process, nonsense-mediated decay	ACCEPT	no		Core NMD process; UPF2 is an essential NMD factor.
human	UPF2	IPR003890	GO:0003723	RNA binding	ACCEPT	no		RNA (spliced mRNA) binding is part of UPF2 engagement with target mRNPs.
human	UPF3A	IPR035979	GO:0003676	nucleic acid binding	KEEP_AS_NON_CORE	yes		Correct but general; the specific GO:0003729 (mRNA binding) better captures UPF3A's RNA-binding activity.
human	UPF3B	IPR039722	GO:0000184	nuclear-transcribed mRNA catabolic process, nonsense-mediated decay	ACCEPT	no		UPF3B is a core NMD factor; this is its central process.
human	UPF3B	IPR035979	GO:0003676	nucleic acid binding	MARK_AS_OVER_ANNOTATED	yes		Uninformative parent term; the specific and supported activity is mRNA binding (GO:0003729).
human	UQCRC1	IPR011249	GO:0046872	metal ion binding	REMOVE	yes		This annotation is based on the M16 peptidase domain architecture, but mammalian UQCRC1 has lost the catalytic metal-binding residues that define active M16 family peptidases. There is no experimental evidence for metal ion binding by human UQCRC1, and UniProt does not annotate any metal binding sites. This represents a case where domain-based inference incorrectly transfers an ancestral function that has been lost in the mammalian lineage.
human	UQCRFS1	IPR005805	GO:0016020	membrane	ACCEPT	no		This is a correct but very generic CC annotation. UQCRFS1 is indeed a membrane protein with a transmembrane helix. More specific annotations (mitochondrial inner membrane) are present from other evidence lines. As a broad IEA it is acceptable to retain, though it adds little information beyond what is captured by the more specific terms.
human	USO1	IPR006953,IPR006955	GO:0006886	intracellular protein transport	KEEP_AS_NON_CORE	yes		Duplicate annotation with different evidence code (also annotated as IBA above). Same rationale applies - too broad, covered by more specific terms. Keep as non-core.
human	USO1	IPR024095	GO:0048193	Golgi vesicle transport	ACCEPT	no		IEA annotation based on InterPro. USO1 functions in both anterograde ER-to-Golgi and retrograde intra-Golgi COPI vesicle transport. Accurate and reasonably specific term for the retrograde function. Accept as core function covering both COPII and COPI vesicle trafficking.
human	USO1	IPR006953	GO:0048280	vesicle fusion with Golgi apparatus	ACCEPT	no		IEA annotation based on InterPro domain. This is highly accurate - USO1 mediates vesicle fusion with Golgi apparatus through SNARE complex assembly and vesicle tethering. This is a core biological process for the protein. Accept as core function.
human	USP10	IPR001394	GO:0016579	protein deubiquitination	ACCEPT	no		Accept as core. Substrate-specific evidence supports deubiquitination of p53, CFTR, ribosomal proteins, LC3B, and immune-signaling substrates.
human	USP21	IPR001394	GO:0016579	protein deubiquitination	ACCEPT	no		Protein deubiquitination is directly demonstrated for multiple human substrates (40S ribosomal proteins, BAZ2A/TIP5); this process annotation is well supported.
human	USP25	IPR001394	GO:0016579	protein deubiquitination	ACCEPT	no		Protein deubiquitination is the direct process outcome of USP25's cysteine-type deubiquitinase activity and is corroborated by multiple experimental studies.
human	VBP1	IPR016655	GO:0006457	protein folding	ACCEPT	no		The IEA annotation to protein folding via InterPro is correct and consistent with higher-confidence IDA and NAS annotations. The PFD3 domain (IPR016655) is specifically associated with the protein folding function of the prefoldin complex (PMID:9630229, PMID:30955883).
human	VBP1	IPR016655	GO:0016272	prefoldin complex	ACCEPT	no		VBP1 is a core structural subunit of the prefoldin complex. The IEA mapping from the PFD3 domain (IPR016655) to prefoldin complex membership is appropriate and consistent with experimental evidence (PMID:9630229, PMID:30955883).
human	VCP	IPR005938	GO:0016787	hydrolase activity	ACCEPT	no		VCP is indeed a hydrolase (ATP hydrolase). While the term is general, it is not wrong and the more specific ATP hydrolysis activity term is also annotated.
human	VEGFA	IPR000072	GO:0016020	membrane	KEEP_AS_NON_CORE	yes		Membrane association is transient during secretion. Primary function is extracellular. This InterPro-based annotation is less informative than specific localization terms.
human	VPS28	IPR007143	GO:0032509	endosome transport via multivesicular body sorting pathway	ACCEPT	no		VPS28/ESCRT-I supports ubiquitin-dependent endosomal receptor/cargo sorting into MVBs and delivery toward lysosomal degradation.
human	VPS4A	IPR003959,IPR003960	GO:0005524	ATP binding	ACCEPT	no		ATP binding is a mechanistic prerequisite for the accepted ATP hydrolysis and ATP-dependent protein-disaggregase activity of VPS4A; it is less specific than hydrolysis but consistent with the core ATPase function.
human	VPS4B	IPR003959,IPR003960	GO:0005524	ATP binding	KEEP_AS_NON_CORE	yes		No direct contradiction was found, but this annotation should not define VPS4B core function.
human	VTI1A	IPR027027	GO:0005484	SNAP receptor activity	ACCEPT	no		VTI1A is a SNARE/SNAP receptor that forms cognate SNARE complexes for membrane fusion and vesicle transport.
human	VTI1A	IPR027027	GO:0005794	Golgi apparatus	ACCEPT	no		This location matches VTI1A SNARE function in Golgi/TGN, endosomal, or trafficking-vesicle membranes.
human	VTI1A	IPR007705	GO:0006886	intracellular protein transport	ACCEPT	no		VTI1A participates in SNARE complexes mediating vesicle fusion and retrograde endosome-to-Golgi/TGN traffic.
human	VTI1A	IPR007705,IPR010989	GO:0016020	membrane	KEEP_AS_NON_CORE	yes		More specific Golgi/TGN, late endosome/endosome, cytoplasmic vesicle, autophagosome, and SNARE-complex annotations capture the core function better.
human	VTI1A	IPR010989,IPR027027	GO:0016192	vesicle-mediated transport	ACCEPT	no		VTI1A participates in SNARE complexes mediating vesicle fusion and retrograde endosome-to-Golgi/TGN traffic.
human	WFS1	IPR026208	GO:0055074	calcium ion homeostasis	ACCEPT	no		Duplicate with IBA annotation above. Both correctly reflect WFS1's core function in calcium homeostasis. The IBA annotation provides stronger phylogenetic support.
human	WT1	IPR000976	GO:0006355	regulation of DNA-templated transcription	ACCEPT	no		Core function. Equivalent to the more specific GO:0006357 (regulation of transcription by RNA Pol II).
human	ZFYVE26	IPR028730	GO:0000281	mitotic cytokinesis	KEEP_AS_NON_CORE	yes		Retain as non-core cytokinesis biology.
human	ZFYVE26	IPR028730	GO:0000724	double-strand break repair via homologous recombination	KEEP_AS_NON_CORE	yes		Retain as non-core experimental DNA-repair context with the caveat that the better-supported core is endolysosomal membrane remodeling.
human	ZFYVE26	IPR028730	GO:0032266	phosphatidylinositol-3-phosphate binding	ACCEPT	no		Retain PI3P binding as the core molecular function that links spastizin to both midbody biology and the proteostasis-relevant endolysosomal membrane-remodeling machinery.
human	ZFYVE26	IPR000306	GO:0046872	metal ion binding	MODIFY	yes	GO:0032266 phosphatidylinositol-3-phosphate binding	Use PI3P binding as the informative molecular-function term for the FYVE domain rather than retaining generic metal ion binding as a core function.
human	ZNF598	IPR044288	GO:0072344	rescue of stalled cytosolic ribosome	ACCEPT	no		Correct; redundant with extensive IDA/IMP evidence.
human	ZSWIM8	IPR007527	GO:0008270	zinc ion binding	KEEP_AS_NON_CORE	yes		The zinc-finger feature supports retention, but the biologically informative core function is substrate-adaptor activity in a CRL rather than generic zinc binding.
mouse	Agtr1a	IPR000190	GO:0004945	angiotensin type II receptor activity	MODIFY	yes	GO:0001596 angiotensin type I receptor activity	The current term is too broad or less precise than angiotensin type I receptor activity for this gene. Replace with angiotensin type I receptor activity to align the annotation with the reviewed evidence.
mouse	Agtr1a	IPR000190,IPR000248,IPR000276,IPR017452	GO:0016020	membrane	KEEP_AS_NON_CORE	yes		This annotation captures a real downstream or context-specific consequence of Agtr1a activity. It should be retained as non-core so it does not obscure the primary receptor/ligand signaling function.
mouse	Agtr1a	IPR000190	GO:0019229	regulation of vasoconstriction	MODIFY	yes	GO:0042310 vasoconstriction	The current term is too broad or less precise than vasoconstriction for this gene. Replace with vasoconstriction to align the annotation with the reviewed evidence.
mouse	Ang2	IPR001427	GO:0003676	nucleic acid binding	MARK_AS_OVER_ANNOTATED	yes		Prefer RNA nuclease activity.
mouse	App	IPR011178,IPR036669	GO:0046914	transition metal ion binding	ACCEPT	no		IEA annotation consistent with known APP functions.
mouse	Bcl2	IPR003093,IPR004725,IPR020717,IPR020726,IPR020728,IPR020731,IPR026298,IPR036834	GO:0042981	regulation of apoptotic process	MODIFY	yes	GO:0043066 negative regulation of apoptotic process	Bcl2 primarily inhibits mitochondrial/intrinsic apoptotic signaling and cytochrome c release. Bcl2 directly controls MOMP at the mitochondrial outer membrane, making it a direct regulator of the intrinsic pathway; the extrinsic pathway annotation does not reflect a direct Bcl2 mechanistic role.
mouse	Camk2a	IPR000719,IPR008271	GO:0004672	protein kinase activity	KEEP_AS_NON_CORE	yes		Specialized cellular process
mouse	Cbl	IPR024159	GO:0001784	phosphotyrosine residue binding	ACCEPT	no		Directly supported core function, process, or location
mouse	Cbl	IPR014741	GO:0005509	calcium ion binding	MARK_AS_OVER_ANNOTATED	yes		Overly broad or uninformative relative to the supported core function
mouse	Cbl	IPR003153,IPR036537	GO:0007166	cell surface receptor signaling pathway	KEEP_AS_NON_CORE	yes		Supported secondary or context-specific role
mouse	Cbl	IPR024162	GO:0023051	regulation of signaling	MODIFY	yes	GO:0042059 negative regulation of epidermal growth factor receptor signaling pathway	Use a more specific GO term supported by the gene product role
mouse	Ccnb1	IPR046965	GO:0016538	cyclin-dependent protein serine/threonine kinase regulator activity	MODIFY	yes	GO:0061575 cyclin-dependent protein serine/threonine kinase activator activity	Cyclin B1 is a non-catalytic CDK1 regulatory/activating cyclin; the replacement term better represents the supported G2/M or CDK-activation role.
mouse	Ccnb1	IPR046965	GO:0044772	mitotic cell cycle phase transition	ACCEPT	no		This term is consistent with cyclin B1 as the regulatory subunit of the cyclin B1-CDK1 complex that drives G2/M and mitotic progression.
mouse	Ccnt1	IPR043198	GO:0006357	regulation of transcription by RNA polymerase II	MODIFY	yes	GO:0032968 positive regulation of transcription elongation by RNA polymerase II	Cyclin T1 acts by activating/targeting CDK9 in P-TEFb for RNA polymerase II pause release, so the proposed replacement captures the mechanism more precisely.
mouse	Ccnt1	IPR043198	GO:0016538	cyclin-dependent protein serine/threonine kinase regulator activity	MODIFY	yes	GO:0061575 cyclin-dependent protein serine/threonine kinase activator activity	Cyclin T1 acts by activating/targeting CDK9 in P-TEFb for RNA polymerase II pause release, so the proposed replacement captures the mechanism more precisely.
mouse	Cdc42	IPR003578	GO:0007264	small GTPase-mediated signal transduction	ACCEPT	no		The term directly reflects Cdc42 GDP/GTP switch activity, effector binding, membrane localization, or immediate actin/polarity outputs.
mouse	Cdk5r1	IPR004944	GO:0016533	protein kinase 5 complex	ACCEPT	no		The term reflects Cdk5r1 as the regulatory activator of CDK5 in neuronal migration, axon guidance, cytoskeletal organization, or synaptic development.
mouse	Cftr	IPR011527	GO:0055085	transmembrane transport	KEEP_AS_NON_CORE	yes		Valid annotation but not the core molecular function
mouse	Cftr	IPR011527	GO:0140359	ABC-type transporter activity	MARK_AS_OVER_ANNOTATED	yes		The ABC transporter activity term implies ATP-driven substrate transport, while CFTR primarily gates passive anion flow using ATP binding/hydrolysis.
mouse	Cyp1a1	IPR001128,IPR002401,IPR008066,IPR017972,IPR036396	GO:0005506	iron ion binding	KEEP_AS_NON_CORE	yes		Necessary cofactor binding but not informative as a core gene function.
mouse	Cyp1a1	IPR001128,IPR002401,IPR017972,IPR036396	GO:0016705	oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen	MODIFY	yes	GO:0016712 oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, reduced flavin or flavoprotein as one donor, and incorporation of one atom of oxygen	Replace with the more specific CYP monooxygenase/paired-donor oxidoreductase term.
mouse	Cyp1a1	IPR001128,IPR002401,IPR008066,IPR036396	GO:0020037	heme binding	KEEP_AS_NON_CORE	yes		Necessary cofactor binding but not informative as a core gene function.
mouse	Dnaja3	IPR012724	GO:0005524	ATP binding	REMOVE	yes		This is a domain-transfer overannotation from DnaJ/Hsp40 family context; the ATPase belongs to the Hsp70 partner, not Dnaja3.
mouse	Dnaja3	IPR008971,IPR012724	GO:0006457	protein folding	ACCEPT	no		"While Dnaja3 does not independently fold proteins, it participates in the protein folding process as a co-chaperone of HSP70. Its chaperone activity on Polg is described as essential for mitochondrial biogenesis (PMID:16327803). The term ""protein folding"" is broad enough to encompass co-chaperone participation in the folding process."
mouse	Dnaja3	IPR012724	GO:0009408	response to heat	MARK_AS_OVER_ANNOTATED	yes		This heat-response annotation is based on DnaJ domain membership, but local evidence supports mitochondrial Hsp70 co-chaperone activity rather than a Dnaja3-specific heat-response role.
mouse	Dnaja3	IPR001305	GO:0031072	heat shock protein binding	ACCEPT	no		Core function. The J domain of Dnaja3 mediates its interaction with HSP70 family member HSPA9 (PMID:14993262). More specific Hsp70 protein binding annotations also exist (GO:0030544).
mouse	Dnaja3	IPR001305,IPR008971,IPR012724	GO:0051082	unfolded protein binding	MODIFY	yes	GO:0044183 protein folding chaperone	GO:0044183 protein folding chaperone captures the DnaJ co-chaperone role more accurately than the vague/proposed-obsolete unfolded-protein-binding term.
mouse	Dnajb11	IPR008971	GO:0006457	protein folding	ACCEPT	no		Secretory-protein folding and maturation are core consequences of the ER Hsp40/BiP cochaperone cycle.
mouse	Dnajb11	IPR008971	GO:0051082	unfolded protein binding	MODIFY	yes	GO:0044183 protein folding chaperone	GO:0044183 protein folding chaperone better captures ERdj3 co-chaperone activity and avoids the obsolete/vague unfolded-protein-binding term.
mouse	Dnmt1	IPR001025	GO:0003682	chromatin binding	ACCEPT	no		Essential for DNMT1 function
mouse	Drd1	IPR000276,IPR017452	GO:0016020	membrane	KEEP_AS_NON_CORE	yes		Drd1 is a multi-pass membrane receptor with neuronal, synaptic, ER/endomembrane trafficking, and ciliary localization evidence. These locations explain where signaling occurs but do not by themselves define the core molecular activity.
mouse	Drd1	IPR001413	GO:0042311	vasodilation	MARK_AS_OVER_ANNOTATED	yes		The annotation either uses an overly generic binding/signaling term, a computationally inferred phenotype, or a downstream physiological outcome. The receptor-specific dopamine/Gs/cAMP annotations capture the gene product function more cleanly.
mouse	Edn1	IPR001928,IPR019764	GO:0019229	regulation of vasoconstriction	MODIFY	yes	GO:0042310 vasoconstriction	The current term is too broad or less precise than vasoconstriction for this gene. Replace with vasoconstriction to align the annotation with the reviewed evidence.
mouse	Ednra	IPR000499,IPR002175	GO:0008217	regulation of blood pressure	KEEP_AS_NON_CORE	yes		This annotation captures a real downstream or context-specific consequence of Ednra activity. It should be retained as non-core so it does not obscure the primary receptor/ligand signaling function.
mouse	Ednra	IPR000276,IPR000499,IPR002175,IPR017452	GO:0016020	membrane	KEEP_AS_NON_CORE	yes		This annotation captures a real downstream or context-specific consequence of Ednra activity. It should be retained as non-core so it does not obscure the primary receptor/ligand signaling function.
mouse	Ednra	IPR000499	GO:0048484	enteric nervous system development	REMOVE	yes		The term appears to reflect either an unsupported transfer, a paralog/family overreach, or a localization/process inconsistent with the curated Ednra biology.
mouse	Egf	IPR001881,IPR018097	GO:0005509	calcium ion binding	KEEP_AS_NON_CORE	yes		Supported secondary or context-specific role
mouse	Egfr	IPR000719,IPR001245,IPR008266	GO:0004672	protein kinase activity	MODIFY	yes	GO:0004714 transmembrane receptor protein tyrosine kinase activity	Use a more specific GO term supported by the gene product role
mouse	Egfr	IPR000719,IPR016245,IPR017441	GO:0005524	ATP binding	ACCEPT	no		Directly supported core function, process, or location
mouse	Egfr	IPR016245	GO:0007169	cell surface receptor protein tyrosine kinase signaling pathway	MODIFY	yes	GO:0007173 epidermal growth factor receptor signaling pathway	Use a more specific GO term supported by the gene product role
mouse	F2rl2	IPR000276	GO:0004930	G protein-coupled receptor activity	ACCEPT	no		PAR3 contains IPR000276 (rhodopsin-like GPCR) and IPR017452 (GPCR 7TM domain).
mouse	F2rl2	IPR000276	GO:0007186	G protein-coupled receptor signaling pathway	ACCEPT	no		Consistent with GPCR family membership and documented signaling functions.
mouse	F2rl2	IPR003912,IPR003943	GO:0007596	blood coagulation	ACCEPT	no		Par3-/- mice are protected against thrombosis, confirming a functional role in coagulation. PAR3 promotes thrombin-mediated activation of PAR4 on platelets.
mouse	F2rl2	IPR003912,IPR003943	GO:0015057	thrombin-activated receptor activity	ACCEPT	no		Thrombin cleaves PAR3 between residues 37-38 to expose the tethered ligand peptide. This is the defining feature of thrombin-activated receptors.
mouse	F2rl2	IPR000276,IPR003912,IPR003943,IPR017452	GO:0016020	membrane	KEEP_AS_NON_CORE	yes		PAR3 is a multi-pass membrane protein, but the plasma membrane annotation is more informative. This broader term is retained as non-core.
mouse	F2rl2	IPR003912,IPR003943	GO:0070493	thrombin-activated receptor signaling pathway	ACCEPT	no		PAR3 is essential for efficient thrombin signaling at low thrombin concentrations in mouse platelets, functioning as a cofactor for PAR4.
mouse	Fyn	IPR000719,IPR017441	GO:0005524	ATP binding	ACCEPT	no		Directly supported core function, process, or location
mouse	Gapdh	IPR006424,IPR020828	GO:0051287	NAD binding	ACCEPT	no		NAD+ is the essential cofactor for GAPDH catalytic activity.
mouse	Gapdh	IPR006424	GO:0050661	NADP binding	REMOVE	yes		GAPDH uses NAD+ not NADP as cofactor. The NADP binding annotation is based on domain similarity but is not functionally accurate for this enzyme.
mouse	Gapdh	IPR006424	GO:0006006	glucose metabolic process	MODIFY	yes	GO:0061621 canonical glycolysis	Too general - more specific glycolysis term should be used.
mouse	Gapdh	IPR006424,IPR020829,IPR020830,IPR020831	GO:0016620	oxidoreductase activity, acting on the aldehyde or oxo group of donors, NAD or NADP as acceptor	MODIFY	yes	GO:0004365 glyceraldehyde-3-phosphate dehydrogenase (NAD+) (phosphorylating) activity	Too general - the specific GAPDH activity term should be used.
mouse	Gas6	IPR000294,IPR001881,IPR018097,IPR035972	GO:0005509	calcium ion binding	KEEP_AS_NON_CORE	yes		Retain as an ancillary molecular property of GAS6, not as the curated core function.
mouse	Ghr	IPR003528	GO:0004896	cytokine receptor activity	MODIFY	yes	GO:0004903 growth hormone receptor activity	Ghr has a specific receptor-activity term that is preferable to the broad cytokine-receptor label.
mouse	Ghr	IPR003528	GO:0016020	membrane	KEEP_AS_NON_CORE	yes		The term is correct but too broad to capture the biology better than the accepted plasma-membrane annotation.
mouse	Grpel2	IPR000740	GO:0000774	adenyl-nucleotide exchange factor activity	ACCEPT	no		This is the closest available molecular-function term for the conserved GrpE role. The annotation should be retained with the paralog-specific caveat that GRPEL2 appears conditional/stress-modulated relative to GRPEL1.
mouse	Grpel2	IPR000740,IPR009012	GO:0006457	protein folding	ACCEPT	no		While protein import into the mitochondrial matrix is the more specific process, Grpel2 does participate in protein folding through its role in regulating mt-Hsp70. The IEA annotation is not incorrect and provides complementary biological context to GO:0030150. As an IEA it is acceptably general.
mouse	Grpel2	IPR000740	GO:0042803	protein homodimerization activity	MARK_AS_OVER_ANNOTATED	yes		While GrpE-family proteins are known to form homodimers, this annotation describes a structural feature rather than the functional molecular activity. Homodimerization is not experimentally verified for Grpel2 specifically, and this IEA may be an over-extension from bacterial GrpE structural data. The core molecular function is GO:0000774 (adenyl-nucleotide exchange factor activity).
mouse	Grpel2	IPR000740	GO:0051087	protein-folding chaperone binding	ACCEPT	no		This annotation correctly captures the binding interaction between Grpel2 and mt-Hsp70. As a nucleotide exchange factor, Grpel2 must physically bind to Hsp70 to catalyze ADP release. This is experimentally supported (PMID:9694873).
mouse	Gulo	IPR007173	GO:0003885	D-arabinono-1,4-lactone oxidase activity	MODIFY	yes	GO:0050105 L-gulonolactone oxidase activity	Mouse Gulo is experimentally supported as L-gulono-1,4-lactone oxidase in vitamin C biosynthesis; D-arabinono-1,4-lactone oxidase activity is not the appropriate specific activity for this mammalian enzyme.
mouse	Gulo	IPR007173	GO:0016020	membrane	MODIFY	yes	GO:0005789 endoplasmic reticulum membrane	The generic membrane term is a true but low-information ancestor of the supported ER/microsomal membrane localization.
mouse	Gulo	IPR010031	GO:0016899	oxidoreductase activity, acting on the CH-OH group of donors, oxygen as acceptor	MODIFY	yes	GO:0050105 L-gulonolactone oxidase activity	Gulo is the FAD-dependent L-gulono-1,4-lactone oxidase in the terminal step of ascorbate biosynthesis, so the specific catalytic term is preferred over this parent term.
mouse	Gulo	IPR006094,IPR036318	GO:0050660	flavin adenine dinucleotide binding	KEEP_AS_NON_CORE	yes		Gulo is an FAD-containing flavoprotein, but the core molecular function is L-gulonolactone oxidase activity.
mouse	Gulo	IPR016166	GO:0071949	FAD binding	KEEP_AS_NON_CORE	yes		The InterPro FAD-binding annotation is consistent with the FAD-dependent enzyme family and experimental expression of an FAD-containing protein, but cofactor binding is not the core function to emphasize.
mouse	Hras	IPR020849	GO:0007165	signal transduction	MODIFY	yes	GO:0007265 Ras protein signal transduction	H-Ras is specifically a Ras-family small GTPase in Ras protein signal transduction.
mouse	Hras	IPR020849	GO:0016020	membrane	MODIFY	yes	GO:0005886 plasma membrane; GO:0000139 Golgi membrane	H-Ras signaling depends on processed and palmitoylated localization at plasma membrane and Golgi/endomembrane compartments.
mouse	Hsp90aa1	IPR001404,IPR019805	GO:0006457	protein folding	ACCEPT	no		This term captures a central molecular activity, process, complex, or main localization of Hsp90aa1.
mouse	Hsp90aa1	IPR001404,IPR019805	GO:0051082	unfolded protein binding	MODIFY	yes	GO:0140662 ATP-dependent protein folding chaperone	Replace with GO:0140662 ATP-dependent protein folding chaperone, which captures the ATP-driven Hsp90 mechanism.
mouse	Hsp90aa1	IPR001404	GO:0140662	ATP-dependent protein folding chaperone	ACCEPT	no		This term captures a central molecular activity, process, complex, or main localization of Hsp90aa1.
mouse	Ifi204	IPR040205	GO:0002218	activation of innate immune response	ACCEPT	no		Correct annotation from InterPro HIN-200 family classification, supported by extensive experimental evidence for innate immune activation.
mouse	Jak1	IPR000719,IPR001245,IPR008266	GO:0004672	protein kinase activity	MARK_AS_OVER_ANNOTATED	yes		The term is true at a broad level but over-annotated because more specific JAK1 tyrosine kinase terms are present.
mouse	Jak1	IPR016251,IPR020776	GO:0016020	membrane	MARK_AS_OVER_ANNOTATED	yes		The term is too broad to add useful information for JAK1 relative to specific tyrosine kinase and JAK-STAT annotations.
mouse	Jak1	IPR016251,IPR020776	GO:0035556	intracellular signal transduction	KEEP_AS_NON_CORE	yes		The annotation is compatible with JAK1 cytokine signaling biology but is not the core molecular function.
mouse	Kras	IPR001806	GO:0003924	GTPase activity	ACCEPT	no		Core Ras-family GTPase switch and membrane-proximal signaling role.
mouse	Kras	IPR001806,IPR005225,IPR020849	GO:0005525	GTP binding	ACCEPT	no		Core Ras-family GTPase switch and membrane-proximal signaling role
mouse	Kras	IPR020849	GO:0007165	signal transduction	MODIFY	yes	GO:0007265 Ras protein signal transduction	KRAS is a Ras-family GTPase switch; the broad signal-transduction parent is less precise than the supported Ras pathway term.
mouse	Kras	IPR020849	GO:0016020	membrane	MARK_AS_OVER_ANNOTATED	yes		KRAS membrane association is real, but the generic membrane term is less informative than the supported plasma membrane and cytoplasmic side of plasma membrane annotations.
mouse	Mapk1	IPR000719,IPR008271	GO:0004672	protein kinase activity	MODIFY	yes	GO:0004707 MAP kinase activity	MAPK1/MAPK3 are ERK-family MAP kinases with proline-directed serine/threonine protein kinase activity.
mouse	Mapk1	IPR000719,IPR003527,IPR008349,IPR017441	GO:0005524	ATP binding	ACCEPT	no		This term directly captures ERK catalytic activity, ERK cascade participation, protein phosphorylation, or canonical nucleo-cytoplasmic localization.
mouse	Mapk3	IPR000719,IPR008271	GO:0004672	protein kinase activity	MODIFY	yes	GO:0004707 MAP kinase activity	MAPK1/MAPK3 are ERK-family MAP kinases with proline-directed serine/threonine protein kinase activity.
mouse	Mapk3	IPR000719,IPR003527,IPR008349,IPR017441	GO:0005524	ATP binding	ACCEPT	no		This term directly captures ERK catalytic activity, ERK cascade participation, protein phosphorylation, or canonical nucleo-cytoplasmic localization.
mouse	Mtor	IPR018936	GO:0016301	kinase activity	MARK_AS_OVER_ANNOTATED	yes		Term is too generic or likely overstates direct mTOR activity relative to specific serine/threonine kinase and TORC terms
mouse	Mtor	IPR009076,IPR036738	GO:0044877	protein-containing complex binding	KEEP_AS_NON_CORE	yes		Valid mTOR-associated context or downstream phenotype, but not the core catalytic TORC function
mouse	Myc	IPR002418,IPR003327,IPR012682	GO:0003700	DNA-binding transcription factor activity	ACCEPT	no		The term directly reflects Myc DNA binding, transcription factor activity, Myc-Max complex formation, or nuclear/chromatin localization.
mouse	Myc	IPR002418,IPR003327,IPR012682	GO:0006355	regulation of DNA-templated transcription	ACCEPT	no		The term directly reflects Myc DNA binding, transcription factor activity, Myc-Max complex formation, or nuclear/chromatin localization.
mouse	Myc	IPR011598,IPR036638	GO:0046983	protein dimerization activity	ACCEPT	no		The term directly reflects Myc DNA binding, transcription factor activity, Myc-Max complex formation, or nuclear/chromatin localization.
mouse	Notch1	IPR001881,IPR018097	GO:0005509	calcium ion binding	ACCEPT	no		Calcium binding is a core molecular function of Notch1. The EGF-like calcium-binding domains (IPR001881) are essential for Notch1 structure and function. UniProt lists calcium ion binding in the domain annotations.
mouse	Notch1	IPR022362	GO:0006355	regulation of DNA-templated transcription	MODIFY	yes	GO:0007221 positive regulation of transcription of Notch receptor target; GO:0045893 positive regulation of DNA-templated transcription	The broad transcription-regulation parent is correct but too general for Notch1. The supported biology is NICD/RBPJ/MAML-dependent positive regulation of canonical Notch target transcription.
mouse	Notch1	IPR008297,IPR010660,IPR011656	GO:0030154	cell differentiation	ACCEPT	no		Cell differentiation regulation is a core biological role of Notch1 signaling. UniProt states Notch1 affects implementation of differentiation, proliferation and apoptotic programs.
mouse	Notch1	IPR022362	GO:0038023	signaling receptor activity	MODIFY	yes	GO:0004888 transmembrane signaling receptor activity	Signaling receptor activity is correct but too generic for Notch1, which is specifically a transmembrane receptor activated by membrane-bound ligands and regulated proteolysis.
mouse	Notch1	IPR008297	GO:0050793	regulation of developmental process	ACCEPT	no		Developmental regulation is a well-established function of Notch1. UniProt notes roles in postimplantation development, mesoderm development, somite formation, and neurogenesis.
mouse	Pld4	IPR001736	GO:0003824	catalytic activity	MODIFY	yes	GO:0045145 single-stranded DNA 5'-3' DNA exonuclease activity; GO:0160121 bis(monoacylglycero)phosphate synthase activity	Replace the generic parent with the specific activities supported by Falcon synthesis and primary biochemical work.
mouse	Pten	IPR017361	GO:0008285	negative regulation of cell population proliferation	KEEP_AS_NON_CORE	yes		Secondary or downstream function
mouse	Pten	IPR045101	GO:0016791	phosphatase activity	MARK_AS_OVER_ANNOTATED	yes		Term is too general
mouse	Pten	IPR017361	GO:0046856	phosphatidylinositol dephosphorylation	ACCEPT	no		Essential PTEN enzymatic activity
mouse	Pten	IPR017361	GO:0051800	phosphatidylinositol-3,4-bisphosphate 3-phosphatase activity	KEEP_AS_NON_CORE	yes		Secondary or downstream function
mouse	Rab7	IPR001806	GO:0003924	GTPase activity	ACCEPT	no		Core molecular function, fundamental to the molecular-switch behavior; directly demonstrated for mouse Rab7 (PMID:16855591).
mouse	Rab7	IPR001806,IPR005225	GO:0005525	GTP binding	ACCEPT	no		Core molecular function of the GTPase cycle.
mouse	Serpinh1	IPR000215,IPR033830	GO:0004867	serine-type endopeptidase inhibitor activity	REMOVE	yes		Same rationale as the IBA annotation for GO:0004867. The InterPro-based inference is incorrect because HSP47 has lost protease inhibitor function despite retaining the serpin fold. This is a well-documented case of neofunctionalization within the serpin superfamily.
mouse	Serpinh1	IPR033830	GO:0005518	collagen binding	ACCEPT	no		Collagen binding is the core molecular function of HSP47. It binds specifically to the triple-helical conformation of collagen, as demonstrated experimentally (PMID:10862616). UniProt names this protein 'Collagen-binding protein' as an alternate name.
mouse	Serpinh1	IPR000215	GO:0005615	extracellular space	REMOVE	yes		HSP47 is an ER-resident protein with a RDEL retention signal (UniProt FT MOTIF 414..417 'Prevents secretion from ER'). The InterPro-based inference from the general serpin family domain is incorrect for this specific member. Its function is entirely intracellular in the ER lumen.
mouse	Sirt2	IPR017328	GO:0051287	NAD binding	ACCEPT	no		Essential for enzymatic mechanism.
mouse	Slc5a1	IPR001734	GO:0022857	transmembrane transporter activity	ACCEPT	no		Correct but uninformative. SGLT1 is a transmembrane transporter. More specific annotations exist so this provides minimal additional information.
mouse	Slc5a1	IPR001734	GO:0016020	membrane	ACCEPT	no		Correct but uninformative. SGLT1 is a multi-pass membrane protein. More specific localizations are better captured by other annotations.
mouse	Slc5a1	IPR001734	GO:0055085	transmembrane transport	ACCEPT	no		Correct but uninformative parent term. More specific transport annotations exist.
mouse	Sox2	IPR022097	GO:0006355	regulation of DNA-templated transcription	ACCEPT	no		This is a valid high-level annotation based on domain architecture. All SOX family transcription factors regulate transcription, and this annotation is appropriately general. While less specific than the positive/negative regulation terms, it is not incorrect.
mouse	Src	IPR000719,IPR017441	GO:0005524	ATP binding	KEEP_AS_NON_CORE	yes		This interaction is mechanistically relevant to SRC signaling but is accessory to the core tyrosine kinase activity.
mouse	Stat1	IPR001217,IPR008967,IPR022752	GO:0003700	DNA-binding transcription factor activity	ACCEPT	no		STAT1 directly binds regulatory DNA elements and functions as a transcription factor downstream of interferon/cytokine signaling.
mouse	Stat1	IPR001217,IPR008967,IPR013799,IPR013800,IPR015988	GO:0006355	regulation of DNA-templated transcription	ACCEPT	no		This term directly reflects STAT1-mediated regulation of target-gene transcription after cytokine-induced activation.
mouse	Stat1	IPR001217,IPR013799,IPR013800,IPR015988	GO:0007165	signal transduction	KEEP_AS_NON_CORE	yes		The annotation is compatible with STAT1 cytokine-response biology but represents a pathway, localization, or downstream process rather than the core molecular function.
mouse	Surf1	IPR002994	GO:0016020	membrane	MODIFY	yes	GO:0005743 mitochondrial inner membrane	SURF1 contains predicted transmembrane helices and functions at the mitochondrial inner membrane as part of COX assembly machinery. Replacing the generic membrane term with GO:0005743 is more informative and consistent with the curated evidence.
mouse	Tert	IPR003545	GO:0000723	telomere maintenance	ACCEPT	no		Core telomerase reverse transcriptase and telomere maintenance function
mouse	Tnfrsf1a	IPR020419	GO:0006693	prostaglandin metabolic process	MARK_AS_OVER_ANNOTATED	yes		This overstates the direct role of the gene product; the curated model is better captured by the specific receptor/ligand, pathway, and supported non-core phenotype terms.
mouse	Tnfrsf1a	IPR020419	GO:0006954	inflammatory response	ACCEPT	no		The term matches a direct molecular function, pathway, or location/physiological output of Tnfrsf1a; it is specific enough to retain without replacement.
mouse	Tnfrsf1a	IPR000488	GO:0007165	signal transduction	MODIFY	yes	GO:0033209 tumor necrosis factor-mediated signaling pathway	The current term is too broad or less precise than tumor necrosis factor-mediated signaling pathway for this gene. Replace with tumor necrosis factor-mediated signaling pathway to align the annotation with the reviewed evidence.
mouse	Top2a	IPR013758	GO:0006259	DNA metabolic process	KEEP_AS_NON_CORE	yes		High-level parent of the specific topological-change process
mouse	Trp53	IPR002117	GO:0006915	apoptotic process	KEEP_AS_NON_CORE	yes		p53 can induce apoptotic programs after stress, but broad apoptosis terms should be retained as non-core because the core Trp53 function is sequence-specific DNA-binding transcriptional regulation.
mouse	Trp53	IPR010991,IPR036674	GO:0051262	protein tetramerization	ACCEPT	no		The term fits the direct p53 activity or a well-established cellular context for that activity, supported by UniProt and the Falcon literature synthesis.
mouse	Tuba1a	IPR002452	GO:0005200	structural constituent of cytoskeleton	ACCEPT	no		Redundant with IBA annotation but correctly assigned. Core function.
mouse	Tuba1a	IPR002452,IPR003008,IPR017975	GO:0005525	GTP binding	ACCEPT	no		Redundant with IBA annotation but correctly assigned. Core function.
mouse	Tuba1a	IPR000217,IPR002452,IPR017975	GO:0007017	microtubule-based process	ACCEPT	no		Correct but very broad. Acceptable as an IEA annotation since more specific terms are also present.
mouse	aldh2	IPR015590,IPR016160,IPR016161,IPR016162,IPR029510	GO:0016491	oxidoreductase activity	MODIFY	yes	GO:0004029 aldehyde dehydrogenase (NAD+) activity	The broad oxidoreductase parent term should be replaced by the directly supported NAD+-dependent aldehyde dehydrogenase activity.
rat	Acot1	IPR016662	GO:0006637	acyl-CoA metabolic process	ACCEPT	no		This term captures a directly supported part of Acot1 core biochemistry or the closest GO process for that activity.
rat	Acot1	IPR016662	GO:0016790	thiolester hydrolase activity	MODIFY	yes	GO:0052816 long-chain fatty acyl-CoA hydrolase activity	The annotation is directionally related to Acot1 but is too broad; the specific long-chain catalytic activity is more informative and is the most specific accurate term already supported in this review.
rat	Aga	IPR000246	GO:0016787	hydrolase activity	MODIFY	yes	GO:0003948 N4-(beta-N-acetylglucosaminyl)-L-asparaginase activity	hydrolase activity is too broad or imprecise for Aga; replace with the more specific supported term(s): GO:0003948 N4-(beta-N-acetylglucosaminyl)-L-asparaginase activity.
rat	Akt1	IPR000719,IPR008271	GO:0004672	protein kinase activity	MODIFY	yes	GO:0004674 protein serine/threonine kinase activity	Replace the transferred ISO term with the specific serine/threonine kinase activity term used for AKT-family biochemistry.
rat	Akt1	IPR000719,IPR000961,IPR017441,IPR017892	GO:0005524	ATP binding	ACCEPT	no		Core AKT1 biochemistry or canonical pathway role is conserved across mammals.
rat	Aldh1l1	IPR011034	GO:0003824	catalytic activity	MODIFY	yes	GO:0016155 formyltetrahydrofolate dehydrogenase activity	catalytic activity is directionally related to Aldh1l1 but should be replaced by the more specific term(s): formyltetrahydrofolate dehydrogenase activity.
rat	Aldh1l1	IPR011407	GO:0005737	cytoplasm	KEEP_AS_NON_CORE	yes		cytoplasm records localization or complex context for Aldh1l1, not the defining molecular function.
rat	Aldh1l1	IPR011407	GO:0006730	one-carbon metabolic process	ACCEPT	no		one-carbon metabolic process is a direct process-level consequence of Aldh1l1's documented role in cytosolic 10-formyltetrahydrofolate oxidation to tetrahydrofolate, CO2, and NADPH.
rat	Aldh1l1	IPR015590,IPR016160,IPR016161,IPR016162,IPR029510	GO:0016491	oxidoreductase activity	MODIFY	yes	GO:0016155 formyltetrahydrofolate dehydrogenase activity	oxidoreductase activity is directionally related to Aldh1l1 but should be replaced by the more specific term(s): formyltetrahydrofolate dehydrogenase activity.
rat	Alpi	IPR001952,IPR018299	GO:0016791	phosphatase activity	MODIFY	yes	GO:0004035 alkaline phosphatase activity	phosphatase activity is directionally correct but less specific than the curated replacement term for Alpi's role in intestinal alkaline phosphatase hydrolysis of phosphate esters.
rat	Amacr	IPR003673	GO:0003824	catalytic activity	MODIFY	yes	GO:0008111 alpha-methylacyl-CoA racemase activity	Generic catalytic activity should be replaced with the specific alpha-methylacyl-CoA racemase activity supported for Amacr.
rat	Aoc1	IPR000269,IPR015798,IPR015800,IPR015802,IPR016182,IPR036460	GO:0005507	copper ion binding	KEEP_AS_NON_CORE	yes		copper ion binding records localization, cofactor/substrate binding, oligomeric state, or physiological context rather than the defining molecular activity of Aoc1.
rat	Aoc1	IPR000269,IPR015798,IPR015800,IPR015802,IPR016182,IPR036460	GO:0009308	amine metabolic process	MODIFY	yes	GO:0009445 putrescine metabolic process; GO:0001695 histamine catabolic process	amine metabolic process is too broad for Aoc1; replace with more specific biological-process term(s): GO:0009445 putrescine metabolic process and GO:0001695 histamine catabolic process, reflecting the enzyme's diamine/histamine deamination role.
rat	Aoc1	IPR000269,IPR015798,IPR015800,IPR015802,IPR016182,IPR036460	GO:0048038	quinone binding	KEEP_AS_NON_CORE	yes		quinone binding records localization, cofactor/substrate binding, oligomeric state, or physiological context rather than the defining molecular activity of Aoc1.
rat	Aprt	IPR005764	GO:0006168	adenine salvage	ACCEPT	no		adenine salvage is directly supported by the curated function of Aprt and is not merely a downstream phenotype or expression response.
rat	Araf	IPR000719,IPR001245,IPR008271	GO:0004672	protein kinase activity	MODIFY	yes	GO:0004709 MAP kinase kinase kinase activity; GO:0004674 protein serine/threonine kinase activity	The current term is too generic or indirect; replace it with the supported MAPKKK/serine-threonine kinase activity or direct protein phosphorylation process.
rat	Araf	IPR000719,IPR017441	GO:0005524	ATP binding	KEEP_AS_NON_CORE	yes		This term describes localization, ATP/cofactor binding, or a secondary signaling context rather than the defining MAPKKK activity.
rat	Araf	IPR003116	GO:0007165	signal transduction	MARK_AS_OVER_ANNOTATED	yes		GO:0007165 signal transduction is a parent of the more specific GO:0035556 intracellular signal transduction, which is already accepted (TAS, PMID:9779826). Retaining the broad automated (IEA) parent alongside the retained specific child is redundant over-annotation.
rat	Cfd	IPR001254,IPR018114	GO:0006508	proteolysis	MODIFY	yes	GO:0004252 serine-type endopeptidase activity; GO:0006957 complement activation, alternative pathway	proteolysis is too broad or imprecise for Cfd; replace with the more specific supported term(s): GO:0004252 serine-type endopeptidase activity; GO:0006957 complement activation, alternative pathway.
rat	Ckmt2	IPR014746	GO:0003824	catalytic activity	MODIFY	yes	GO:0004111 creatine kinase activity	The annotation is directionally related to Ckmt2 but is too broad; the specific catalytic activity is more informative.
rat	Ckmt2	IPR022413,IPR022414,IPR022415,IPR036802	GO:0016301	kinase activity	MODIFY	yes	GO:0004111 creatine kinase activity	The annotation is directionally related to Ckmt2 but is too broad; the specific catalytic activity is more informative.
rat	Ckmt2	IPR022413,IPR022414,IPR022415,IPR036802	GO:0016772	transferase activity, transferring phosphorus-containing groups	MODIFY	yes	GO:0004111 creatine kinase activity	The annotation is directionally related to Ckmt2 but is too broad; the specific catalytic activity is more informative.
rat	Ckmt2	IPR000749	GO:0016775	phosphotransferase activity, nitrogenous group as acceptor	MODIFY	yes	GO:0004111 creatine kinase activity	The annotation is directionally related to Ckmt2 but is too broad; the specific catalytic activity is more informative.
rat	Ckmt2	IPR000749	GO:0046314	phosphocreatine biosynthetic process	ACCEPT	no		This term captures a directly supported part of Ckmt2 core biochemistry or the closest GO process for that activity.
rat	Crot	IPR000542	GO:0016746	acyltransferase activity	MODIFY	yes	GO:0008458 carnitine O-octanoyltransferase activity	acyltransferase activity is directionally related to Crot but should be replaced by the more specific term(s): carnitine O-octanoyltransferase activity.
rat	Cyb5r3	IPR001433,IPR001709,IPR001834,IPR017927	GO:0016491	oxidoreductase activity	MODIFY	yes	GO:0090524 cytochrome-b5 reductase activity, acting on NADH	oxidoreductase activity is directionally related to Cyb5r3 but should be replaced by the more specific term(s): cytochrome-b5 reductase activity, acting on NADH.
rat	Cyp2a1	IPR001128,IPR002401,IPR008067,IPR036396	GO:0004497	monooxygenase activity	ACCEPT	no		This term is directly compatible with Cyp2a1 as a heme P450 monooxygenase/steroid hydroxylase involved in xenobiotic and coumarin metabolism.
rat	Cyp2a1	IPR001128,IPR002401,IPR008067,IPR017972,IPR036396	GO:0005506	iron ion binding	ACCEPT	no		This term is directly compatible with Cyp2a1 as a heme P450 monooxygenase/steroid hydroxylase involved in xenobiotic and coumarin metabolism.
rat	Cyp2a1	IPR001128,IPR002401,IPR017972,IPR036396	GO:0016705	oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen	MODIFY	yes	GO:0016712 oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, reduced flavin or flavoprotein as one donor, and incorporation of one atom of oxygen	The oxidoreductase term is too generic for Cyp2a1 and should be replaced with the supported P450/steroid hydroxylase activity.
rat	Cyp2a1	IPR001128,IPR002401,IPR008067,IPR036396	GO:0020037	heme binding	ACCEPT	no		This term is directly compatible with Cyp2a1 as a heme P450 monooxygenase/steroid hydroxylase involved in xenobiotic and coumarin metabolism.
rat	Cyp2d10	IPR001128,IPR002401,IPR008069,IPR017972,IPR036396	GO:0005506	iron ion binding	KEEP_AS_NON_CORE	yes		iron ion binding records substrate, cofactor, or quaternary-structure context for Cyp2d10, but the curated core function is cytochrome P450 monooxygenase metabolism of xenobiotic substrates.
rat	Cyp2d10	IPR001128,IPR002401,IPR017972,IPR036396	GO:0016705	oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen	MODIFY	yes	GO:0004497 monooxygenase activity	oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen is directionally correct but less specific than the curated replacement term for Cyp2d10's role in cytochrome P450 monooxygenase metabolism of xenobiotic substrates.
rat	Cyp2d10	IPR001128,IPR002401,IPR008069,IPR036396	GO:0020037	heme binding	KEEP_AS_NON_CORE	yes		heme binding records substrate, cofactor, or quaternary-structure context for Cyp2d10, but the curated core function is cytochrome P450 monooxygenase metabolism of xenobiotic substrates.
rat	Cyp4b1	IPR001128,IPR002401,IPR017972,IPR036396	GO:0005506	iron ion binding	KEEP_AS_NON_CORE	yes		iron ion binding records substrate, cofactor, or quaternary-structure context for Cyp4b1, but the curated core function is cytochrome P450 monooxygenase activation and metabolism of xenobiotic substrates.
rat	Cyp4b1	IPR001128,IPR002401,IPR017972,IPR036396	GO:0016705	oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen	MODIFY	yes	GO:0004497 monooxygenase activity	oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen is directionally correct but less specific than the curated replacement term for Cyp4b1's role in cytochrome P450 monooxygenase activation and metabolism of xenobiotic substrates.
rat	Cyp4b1	IPR001128,IPR002401,IPR036396	GO:0020037	heme binding	KEEP_AS_NON_CORE	yes		heme binding records substrate, cofactor, or quaternary-structure context for Cyp4b1, but the curated core function is cytochrome P450 monooxygenase activation and metabolism of xenobiotic substrates.
rat	Ddo	IPR006181,IPR023209	GO:0003884	D-amino-acid oxidase activity	MODIFY	yes	GO:0008445 D-aspartate oxidase activity	The annotation is directionally related to Ddo but is too broad; the specific catalytic activity is more informative.
rat	Ddo	IPR023209	GO:0046416	D-amino acid metabolic process	KEEP_AS_NON_CORE	yes		The annotation is compatible with Ddo biology but is broader or more contextual than the core molecular function.
rat	Echs1	IPR018376	GO:0003824	catalytic activity	MODIFY	yes	GO:0004300 enoyl-CoA hydratase activity; GO:0004165 delta(3)-delta(2)-enoyl-CoA isomerase activity	catalytic activity is directionally related to Echs1 but should be replaced by the more specific term(s): enoyl-CoA hydratase activity, delta(3)-delta(2)-enoyl-CoA isomerase activity.
rat	Egfr	IPR000719,IPR001245,IPR008266	GO:0004672	protein kinase activity	MARK_AS_OVER_ANNOTATED	yes		Overly generic; subsumed by the specific GO:0004714 / GO:0004713 tyrosine kinase annotations.
rat	Egfr	IPR016245,IPR020635	GO:0004713	protein tyrosine kinase activity	MARK_AS_OVER_ANNOTATED	yes		Overly generic; subsumed by and uninformative relative to the more specific GO:0004714 (its direct child), consistent with the treatment of the analogous generic parent GO:0004672 (protein kinase activity).
rat	Egfr	IPR016245	GO:0016020	membrane	MARK_AS_OVER_ANNOTATED	yes		Overly generic; the informative localization is plasma membrane.
rat	Ephx1	IPR000639	GO:0003824	catalytic activity	MODIFY	yes	GO:0004301 epoxide hydrolase activity	catalytic activity is directionally correct but less specific than the curated replacement term for Ephx1's role in microsomal epoxide hydrolase detoxification of arene and fatty-acid epoxides.
rat	Ephx1	IPR016292	GO:0016803	ether hydrolase activity	MODIFY	yes	GO:0004301 epoxide hydrolase activity	ether hydrolase activity is directionally correct but less specific than the curated replacement term for Ephx1's role in microsomal epoxide hydrolase detoxification of arene and fatty-acid epoxides.
rat	Ghr	IPR003528	GO:0004896	cytokine receptor activity	KEEP_AS_NON_CORE	yes		Accurate parent term but subsumed by GO:0004903.
rat	Gss	IPR004887,IPR005615,IPR014042,IPR014049,IPR037013	GO:0005524	ATP binding	KEEP_AS_NON_CORE	yes		ATP binding records localization, cofactor/substrate binding, oligomeric state, or physiological context rather than the defining molecular activity of Gss.
rat	Gss	IPR014042	GO:0016874	ligase activity	MODIFY	yes	GO:0004363 glutathione synthase activity	ligase activity is too broad or imprecise for Gss; replace with the more specific supported term(s): GO:0004363 glutathione synthase activity.
rat	Hdc	IPR010977	GO:0006520	amino acid metabolic process	MODIFY	yes	GO:0004398 histidine decarboxylase activity	amino acid metabolic process is directionally related to Hdc but should be replaced by the more specific term(s): histidine decarboxylase activity.
rat	Hdc	IPR002129	GO:0016830	carbon-carbon lyase activity	MODIFY	yes	GO:0004398 histidine decarboxylase activity	carbon-carbon lyase activity is directionally related to Hdc but should be replaced by the more specific term(s): histidine decarboxylase activity.
rat	Hmgcs2	IPR000590,IPR010122	GO:0008299	isoprenoid biosynthetic process	REMOVE	yes		Paralog conflation in InterPro2GO mapping. The mitochondrial isoform feeds ketogenesis, not isoprenoid biosynthesis.
rat	Hmgcs2	IPR013746	GO:0010142	farnesyl diphosphate biosynthetic process, mevalonate pathway	REMOVE	yes		Paralog conflation -- applies to cytosolic HMGCS1, not mitochondrial HMGCS2.
rat	Hmgcs2	IPR016039	GO:0016746	acyltransferase activity	REMOVE	yes		Redundant with the more specific GO:0004421 annotation.
rat	Klk9	IPR001254,IPR018114	GO:0006508	proteolysis	KEEP_AS_NON_CORE	yes		The annotation is compatible with Klk9 biology but is broader or more contextual than the core molecular function.
rat	Ldhb	IPR015955	GO:0003824	catalytic activity	MODIFY	yes	GO:0004459 L-lactate dehydrogenase (NAD+) activity	catalytic activity is directionally related to Ldhb but should be replaced by the more specific term(s): L-lactate dehydrogenase (NAD+) activity.
rat	Ldhb	IPR001236	GO:0016491	oxidoreductase activity	MODIFY	yes	GO:0004459 L-lactate dehydrogenase (NAD+) activity	oxidoreductase activity is directionally related to Ldhb but should be replaced by the more specific term(s): L-lactate dehydrogenase (NAD+) activity.
rat	Ldhb	IPR001557,IPR015955,IPR022383	GO:0016616	oxidoreductase activity, acting on the CH-OH group of donors, NAD or NADP as acceptor	MODIFY	yes	GO:0004459 L-lactate dehydrogenase (NAD+) activity	oxidoreductase activity, acting on the CH-OH group of donors, NAD or NADP as acceptor is directionally related to Ldhb but should be replaced by the more specific term(s): L-lactate dehydrogenase (NAD+) activity.
rat	Lss	IPR018333	GO:0005811	lipid droplet	KEEP_AS_NON_CORE	yes		lipid droplet records localization, cofactor/substrate binding, oligomeric state, or physiological context rather than the defining molecular activity of Lss.
rat	Lss	IPR018333	GO:0016104	triterpenoid biosynthetic process	ACCEPT	no		triterpenoid biosynthetic process is directly supported by the curated function of Lss and is not merely a downstream phenotype or expression response.
rat	Lss	IPR002365,IPR018333	GO:0016866	intramolecular transferase activity	MODIFY	yes	GO:0000250 lanosterol synthase activity	intramolecular transferase activity is too broad or imprecise for Lss; replace with the more specific supported term(s): GO:0000250 lanosterol synthase activity.
rat	Mapk1	IPR000719,IPR008271	GO:0004672	protein kinase activity	MARK_AS_OVER_ANNOTATED	yes		Over-general. The specific MF terms (MAP kinase activity, protein serine/threonine kinase activity) are present and preferred.
rat	Mapk1	IPR000719,IPR003527,IPR008349,IPR017441	GO:0005524	ATP binding	ACCEPT	no		Core molecular function. ATP binding is required for the phosphotransfer reaction; experimentally demonstrated (PMID:15027896) and assay-confirmed in the deep research.
rat	Nat8l	IPR050769	GO:0008080	N-acetyltransferase activity	MODIFY	yes	GO:0017188 L-aspartate N-acetyltransferase activity	The annotation is directionally related to Nat8l but is too broad; the specific catalytic activity is more informative.
rat	Nat8l	IPR000182	GO:0016747	acyltransferase activity, transferring groups other than amino-acyl groups	MODIFY	yes	GO:0017188 L-aspartate N-acetyltransferase activity	The annotation is directionally related to Nat8l but is too broad; the specific catalytic activity is more informative.
rat	Pfkfb4	IPR001345,IPR003094	GO:0003824	catalytic activity	MODIFY	yes	GO:0003873 6-phosphofructo-2-kinase activity; GO:0004331 fructose-2,6-bisphosphate 2-phosphatase activity	catalytic activity is directionally related to Pfkfb4 but should be replaced by the more specific term(s): 6-phosphofructo-2-kinase activity, fructose-2,6-bisphosphate 2-phosphatase activity.
rat	Pfkfb4	IPR003094,IPR013079	GO:0005524	ATP binding	KEEP_AS_NON_CORE	yes		ATP binding records cofactor, substrate, or interaction context for Pfkfb4, but the curated core role is bifunctional synthesis and degradation of fructose 2,6-bisphosphate.
rat	Pfkfb4	IPR013079	GO:0006000	fructose metabolic process	ACCEPT	no		fructose metabolic process is a direct process-level consequence of Pfkfb4's documented role in bifunctional synthesis and degradation of fructose 2,6-bisphosphate.
rat	Pfkfb4	IPR003094	GO:0006003	fructose 2,6-bisphosphate metabolic process	ACCEPT	no		fructose 2,6-bisphosphate metabolic process is a direct process-level consequence of Pfkfb4's documented role in bifunctional synthesis and degradation of fructose 2,6-bisphosphate.
rat	Pgam2	IPR001345	GO:0003824	catalytic activity	MODIFY	yes	GO:0004619 phosphoglycerate mutase activity	catalytic activity is directionally correct but less specific than the curated replacement term for Pgam2's role in phosphoglycerate and bisphosphoglycerate mutase reactions in glycolysis.
rat	Pgam2	IPR005952	GO:0016868	intramolecular phosphotransferase activity	MODIFY	yes	GO:0004619 phosphoglycerate mutase activity	intramolecular phosphotransferase activity is directionally correct but less specific than the curated replacement term for Pgam2's role in phosphoglycerate and bisphosphoglycerate mutase reactions in glycolysis.
rat	Pgp	IPR006349	GO:0016791	phosphatase activity	MODIFY	yes	GO:0043136 sn-glycerol 3-phosphatase activity	The annotation is directionally related to Pgp but is too broad; the specific catalytic activity is more informative.
rat	Pnlip	IPR002331,IPR016272,IPR033906	GO:0006629	lipid metabolic process	MODIFY	yes	GO:0019433 triglyceride catabolic process; GO:0001523 retinoid metabolic process	lipid metabolic process is too broad or imprecise for Pnlip; replace with the more specific supported term(s): GO:0019433 triglyceride catabolic process; GO:0001523 retinoid metabolic process.
rat	Pnlip	IPR016272	GO:0052689	carboxylic ester hydrolase activity	MODIFY	yes	GO:0004806 triacylglycerol lipase activity; GO:0047376 all-trans-retinyl-palmitate hydrolase, all-trans-retinol forming activity	carboxylic ester hydrolase activity is too broad or imprecise for Pnlip; replace with the more specific supported term(s): GO:0004806 triacylglycerol lipase activity; GO:0047376 all-trans-retinyl-palmitate hydrolase, all-trans-retinol forming activity.
rat	Ppp3r1	IPR002048	GO:0005509	calcium ion binding	ACCEPT	no		Ppp3r1/CnB1 contains four EF-hand calcium-binding motifs (UniProt; PDB 4IL1) that directly bind Ca2+; this is a defining molecular function of the protein, supported by structural and review evidence.
rat	Prkaa2	IPR000719,IPR008271	GO:0004672	protein kinase activity	REMOVE	yes		Too general - more specific terms available (serine/threonine kinase, AMP-activated protein kinase). Redundant with better-annotated specific terms.
rat	Rgn	IPR008367	GO:0005509	calcium ion binding	ACCEPT	no		Duplicate of the IBA annotation above, both are correct. IEA based on InterPro domains aligns with experimental evidence. Calcium binding is a well-established core function.
rat	Rgn	IPR008367	GO:0030234	enzyme regulator activity	MARK_AS_OVER_ANNOTATED	yes		Generic enzyme regulator activity is superseded by the specific regulator-activity terms already annotated; retaining it as core would be an over-annotation.
rat	Rnase1	IPR001427	GO:0003676	nucleic acid binding	MODIFY	yes	GO:0004522 ribonuclease A activity	The annotation is directionally related to Rnase1 but is too broad; the specific catalytic activity is more informative.
rat	Slc13a2	IPR001898	GO:0016020	membrane	KEEP_AS_NON_CORE	yes		This term records supported membrane or apical plasma-membrane localization rather than the defining transport activity.
rat	Slc13a2	IPR001898	GO:0022857	transmembrane transporter activity	MODIFY	yes	GO:0017153 sodium:dicarboxylate symporter activity	The generic transporter or transport term should be replaced with the specific sodium:dicarboxylate symporter activity or substrate-specific dicarboxylate transport processes.
rat	Slc13a2	IPR001898	GO:0055085	transmembrane transport	MODIFY	yes	GO:0071422 succinate transmembrane transport; GO:0015741 fumarate transport; GO:0015742 alpha-ketoglutarate transport; GO:0015746 citrate transport	The generic transporter or transport term should be replaced with the specific sodium:dicarboxylate symporter activity or substrate-specific dicarboxylate transport processes.
rat	Slc5a1	IPR001734	GO:0016020	membrane	MARK_AS_OVER_ANNOTATED	yes		This is too general to be informative. SGLT1 has specific annotations to apical plasma membrane and brush border membrane that are much more informative. While technically correct, this adds no useful information.
rat	Slc5a1	IPR001734	GO:0022857	transmembrane transporter activity	MARK_AS_OVER_ANNOTATED	yes		Far too general to be informative. Specific molecular function annotations (D-glucose:sodium symporter activity) provide the relevant information.
rat	Slc5a1	IPR001734	GO:0055085	transmembrane transport	MARK_AS_OVER_ANNOTATED	yes		Far too general to be informative. Specific process annotations provide the relevant information about SGLT1 function.
rat	Sqle	IPR013698	GO:0050660	flavin adenine dinucleotide binding	KEEP_AS_NON_CORE	yes		This term records subcellular location, FAD/cofactor binding, membrane association, or lipid-droplet context rather than the defining catalytic function.
rat	Sstr5	IPR000586,IPR001184	GO:0004994	somatostatin receptor activity	ACCEPT	no		Automated annotation from domain signatures that is accurate for this well-characterized somatostatin receptor.
rat	Sstr5	IPR000276	GO:0004930	G protein-coupled receptor activity	KEEP_AS_NON_CORE	yes		Accurate but redundant with the more specific somatostatin receptor activity annotation. The parent GPCR activity term is implied by the child term.
rat	Sstr5	IPR000276,IPR000586,IPR001184	GO:0007186	G protein-coupled receptor signaling pathway	KEEP_AS_NON_CORE	yes		Subsumed by the more specific GO:0007193 annotation that is supported by IDA evidence.
rat	Sstr5	IPR000276,IPR000586,IPR001184,IPR017452	GO:0016020	membrane	KEEP_AS_NON_CORE	yes		Too general; plasma membrane (GO:0005886) is more appropriate and already annotated.
rat	St13	IPR034649	GO:0046983	protein dimerization activity	MARK_AS_OVER_ANNOTATED	yes		While Hip does self-associate (forming tetramers via its N-terminal dimerization domain), protein dimerization activity is a structural feature rather than the functional molecular activity of interest. The core function is Hsp70 protein binding (GO:0030544), and the self-association is a prerequisite for this function rather than the function itself.
rat	Tp53	IPR011615	GO:0000976	transcription cis-regulatory region binding	KEEP_AS_NON_CORE	yes		Correct but generic; superseded by the more specific DNA-binding terms.
rat	Tp53	IPR002117,IPR012346	GO:0003677	DNA binding	KEEP_AS_NON_CORE	yes		Correct but uninformatively generic; more specific terms preferred.
rat	Tp53	IPR002117,IPR008967,IPR012346	GO:0003700	DNA-binding transcription factor activity	KEEP_AS_NON_CORE	yes		Generic parent of the core MF term GO:0000981.
rat	Tp53	IPR002117,IPR008967,IPR012346	GO:0006355	regulation of DNA-templated transcription	KEEP_AS_NON_CORE	yes		Correct but generic parent of the more specific Pol II regulation terms.
rat	Tp53	IPR002117	GO:0006915	apoptotic process	KEEP_AS_NON_CORE	yes		Generic; the p53-mediated intrinsic apoptosis terms capture the core role.
rat	Tp53	IPR010991,IPR036674	GO:0051262	protein tetramerization	ACCEPT	no		Tetramerization is an experimentally established, functionally required property of p53.
rat	Uggt1	IPR009448	GO:0009101	glycoprotein biosynthetic process	KEEP_AS_NON_CORE	yes		Kept as non-core to preserve potentially valid context-specific annotation without elevating it to core function.
rat	Ugt2a1	IPR002213	GO:0008194	UDP-glycosyltransferase activity	MODIFY	yes	GO:0015020 glucuronosyltransferase activity	UDP-glycosyltransferase activity is too broad or imprecise for Ugt2a1; replace with the more specific supported term(s): GO:0015020 glucuronosyltransferase activity.
worm	aak-2	IPR000719,IPR008271	GO:0004672	protein kinase activity	ACCEPT	no		Correct but redundant with the more specific GO:0004674 (protein serine/threonine kinase activity) and GO:0004679 (AMPK activity). Retained as a general IEA annotation.
worm	atf-4	IPR004827,IPR046347	GO:0003700	DNA-binding transcription factor activity	ACCEPT	no		Correct InterPro-based annotation. The bZIP domain definitively establishes ATF-4 as a DNA-binding transcription factor, and experimental evidence confirms this function.
worm	atf-4	IPR004827,IPR046347	GO:0006355	regulation of DNA-templated transcription	ACCEPT	no		Correct annotation capturing ATF-4's regulatory role in transcription. Consistent with more specific annotations for RNA polymerase II transcription regulation.
worm	atf-6	IPR004827,IPR046347	GO:0003700	DNA-binding transcription factor activity	ACCEPT	no		The IEA annotation is correct. ATF-6 belongs to the bZIP family and has been experimentally demonstrated to regulate transcription of target genes in C. elegans.
worm	atf-6	IPR004827,IPR046347	GO:0006355	regulation of DNA-templated transcription	ACCEPT	no		This annotation is correct and supported by experimental evidence showing ATF-6 regulates transcription of UPR genes.
worm	atf-7	IPR004827,IPR046347	GO:0003700	DNA-binding transcription factor activity	ACCEPT	no		This IEA annotation based on InterPro is correct but less specific than the IBA annotation for RNA polymerase II-specific DNA-binding TF activity. Both are valid and supported by experimental evidence.
worm	atf-7	IPR004827,IPR046347	GO:0006355	regulation of DNA-templated transcription	ACCEPT	no		Correct annotation based on domain analysis. ATF-7 functions as a transcriptional regulator, both repressing and activating transcription depending on its phosphorylation state.
worm	atfs-1	IPR004827	GO:0003700	DNA-binding transcription factor activity	ACCEPT	no		Correct annotation based on domain architecture. The bZIP domain confers DNA-binding transcription factor activity. More specific terms are also present.
worm	atfs-1	IPR004827	GO:0006355	regulation of DNA-templated transcription	ACCEPT	no		Correct annotation based on bZIP domain function. ATFS-1 is a well-characterized transcriptional regulator.
worm	bbs-1	IPR028784	GO:0034464	BBSome	ACCEPT	no		Correct annotation supported by domain architecture and experimental evidence. InterPro domain IPR028784 (BBS1) correctly identifies this as a BBSome component.
worm	bbs-1	IPR028784	GO:1905515	non-motile cilium assembly	ACCEPT	no		Correct annotation consistent with experimental evidence showing BBS-1 is required for cilia biogenesis.
worm	bbs-2	IPR016616	GO:0034464	BBSome	ACCEPT	no		This is a duplicate of the IBA annotation for BBSome membership, both are correct. The InterPro domain (IPR016616, Bardet-Biedl syndrome 2 protein) correctly predicts BBSome membership, which is experimentally validated.
worm	bbs-2	IPR016616	GO:1905515	non-motile cilium assembly	ACCEPT	no		This is the most precise cilium assembly term for C. elegans BBS-2. All cilia in C. elegans are non-motile sensory cilia. The BBSome is required for their assembly through its role in IFT particle organization. This is more specific than the general 'cilium assembly' term and accurately reflects the worm biology.
worm	bbs-5	IPR006606	GO:0034464	BBSome	ACCEPT	no		While redundant with the IBA annotation, this provides independent computational evidence for BBSome membership based on domain architecture. Both annotations are valid.
worm	bbs-7	IPR016575	GO:0034464	BBSome	ACCEPT	no		Correct annotation consistent with IBA and experimental evidence. Retaining both IEA and IBA annotations is appropriate as they derive from independent evidence sources.
worm	bbs-7	IPR016575	GO:1905515	non-motile cilium assembly	ACCEPT	no		Appropriate annotation. C. elegans sensory neurons have non-motile (primary) cilia, and BBS-7 is required for their proper assembly. This is more specific than the general 'cilium assembly' term.
worm	bbs-8	IPR028796	GO:0034464	BBSome	ACCEPT	no		Correct. This IEA annotation is redundant with the IBA annotation but provides independent computational support for BBSome membership.
worm	bbs-8	IPR028796	GO:1905515	non-motile cilium assembly	ACCEPT	no		Correct. Redundant with IBA annotation but provides additional computational support.
worm	cebp-2	IPR004827,IPR031106,IPR046347	GO:0003700	DNA-binding transcription factor activity	ACCEPT	no		This annotation is accurate based on domain architecture and is consistent with the more specific GO:0000981 annotation. IEA annotations from InterPro are reliable for well-characterized domain families like bZIP.
worm	cgh-1	IPR011545	GO:0003676	nucleic acid binding	ACCEPT	no		The InterPro domain-based annotation is correct - DEAD box helicases bind nucleic acids. This is redundant with but not contradicted by the more specific mRNA binding annotation.
worm	che-3	IPR004273,IPR026983	GO:0007018	microtubule-based movement	ACCEPT	no		Accurate annotation. CHE-3 powers microtubule-based movement during retrograde IFT. The more specific term GO:0035721 (intraciliary retrograde transport) provides greater precision for the biological context.
worm	che-3	IPR004273	GO:0008569	minus-end-directed microtubule motor activity	ACCEPT	no		Same term as IBA annotation above. The IEA from InterPro correctly identifies CHE-3 as a minus-end-directed motor based on its dynein heavy chain domain structure.
worm	che-3	IPR026983	GO:0045505	dynein intermediate chain binding	ACCEPT	no		Same term as IBA annotation. The IEA from InterPro correctly identifies this binding function based on dynein heavy chain domain structure.
worm	che-3	IPR026983	GO:0051959	dynein light intermediate chain binding	ACCEPT	no		Same term as IBA annotation. Consistent with dynein complex architecture.
worm	clec-60		GO:0030246	carbohydrate binding	NEW	no		While not explicitly present in the GOA file, the carbohydrate binding activity is strongly supported by the domain composition of CLEC-60. The UniProt record shows C-type lectin domain annotations from multiple sources (CDD, Gene3D, InterPro, PANTHER, SMART, SUPFAM). This molecular function is mechanistically linked to its biological role in pathogen recognition and defense. C-type lectins typically bind carbohydrates in a calcium-dependent manner and can recognize pathogen-associated molecular patterns such as bacterial cell wall components.
worm	clec-60		GO:0005576	extracellular region	NEW	no		The UniProt record shows a predicted signal peptide at residues 1-17, strongly suggesting that CLEC-60 is a secreted protein. This cellular component annotation is important for understanding its function as an extracellular antimicrobial effector that would encounter pathogens in the intestinal lumen.
worm	clpp-1	IPR001907	GO:0004176	ATP-dependent peptidase activity	ACCEPT	no		This IEA annotation is redundant with the IBA annotation for the same term but is acceptable. The InterPro-based inference correctly identifies ATP-dependent peptidase activity based on the conserved ClpP domain.
worm	cmd-1	IPR002048	GO:0005509	calcium ion binding	ACCEPT	no		This is a correct electronic annotation for a canonical EF-hand calcium- binding protein and matches core function.
worm	csr-1	IPR049636	GO:0000978	RNA polymerase II cis-regulatory region sequence-specific DNA binding	REMOVE	yes		Gene identity error. CSR-1 lacks DNA-binding transcription factor domains; it contains PAZ and PIWI domains characteristic of Argonaute proteins.
worm	csr-1	IPR001628	GO:0003700	DNA-binding transcription factor activity	REMOVE	yes		Gene identity error. CSR-1 is not a transcription factor.
worm	csr-1	IPR001628,IPR013088	GO:0006355	regulation of DNA-templated transcription	REMOVE	yes		Gene identity error. CSR-1 may influence chromatin state through its RNAi-related functions but this annotation is based on nuclear receptor domains that CSR-1 lacks.
worm	csr-1	IPR001628	GO:0043565	sequence-specific DNA binding	REMOVE	yes		Gene identity error. CSR-1 binds RNA (22G-RNAs), not DNA.
worm	daf-16	IPR001766,IPR030456	GO:0003700	DNA-binding transcription factor activity	ACCEPT	no		This is the fundamental molecular function of DAF-16. IEA from InterPro is consistent with experimental evidence.
worm	daf-16	IPR001766,IPR030456	GO:0006355	regulation of DNA-templated transcription	ACCEPT	no		Core function of DAF-16. Regulates transcription of numerous target genes involved in longevity, stress response, and metabolism.
worm	daf-16	IPR001766,IPR030456	GO:0043565	sequence-specific DNA binding	ACCEPT	no		Sequence-specific binding via forkhead domain is core to DAF-16 function. InterPro annotation consistent with experimental data.
worm	daf-19	IPR039779	GO:0003700	DNA-binding transcription factor activity	ACCEPT	no		This IEA annotation is accurate but is a broader parent of the more specific GO:0000981 annotation. DAF-19 belongs to the RFX transcription factor family as annotated by InterPro.
worm	daf-19	IPR003150	GO:0006355	regulation of DNA-templated transcription	ACCEPT	no		This annotation is accurate. The more specific GO:0006357 annotation better captures DAF-19's role in RNA polymerase II-dependent transcription.
worm	daf-2	IPR000719,IPR001245,IPR008266	GO:0004672	protein kinase activity	MODIFY	yes	GO:0004714 transmembrane receptor protein tyrosine kinase activity	The more specific term protein tyrosine kinase activity (GO:0004713) or transmembrane receptor protein tyrosine kinase activity (GO:0004714) should be used instead, as DAF-2 is specifically a tyrosine kinase.
worm	daf-21	IPR001404	GO:0006457	protein folding	ACCEPT	no		Duplicate annotation for protein folding, a core HSP90 function supported by multiple evidence types.
worm	daf-21	IPR001404	GO:0016887	ATP hydrolysis activity	ACCEPT	no		Duplicate annotation for ATPase activity, supported by direct biochemical measurements (PMID:21980476, PMID:19559711).
worm	daf-21	IPR001404	GO:0051082	unfolded protein binding	MODIFY	yes	GO:0044183 protein folding chaperone	GO:0051082 is proposed for obsoletion. DAF-21/HSP90 is an ATP-dependent foldase chaperone. The appropriate replacement term is GO:0044183 (protein folding chaperone). Consistent with MODIFY on IBA annotation.
worm	daf-21	IPR001404	GO:0140662	ATP-dependent protein folding chaperone	ACCEPT	no		This term precisely describes DAF-21 function - it is an ATP-dependent chaperone that promotes protein folding. Well supported by experimental evidence.
worm	dct-1	IPR010548	GO:0005740	mitochondrial envelope	ACCEPT	no		Correct annotation at appropriate specificity. The mitochondrial envelope includes the outer membrane where DCT-1 is localized. This is consistent with experimental data.
worm	dct-1	IPR010548	GO:0016020	membrane	ACCEPT	no		Correct but very broad annotation. DCT-1 contains a transmembrane domain and is an integral membrane protein. More specific annotations (mitochondrial outer membrane) are also present.
worm	dct-1	IPR010548	GO:0043065	positive regulation of apoptotic process	KEEP_AS_NON_CORE	yes		DCT-1 has pro-apoptotic activity when overexpressed, consistent with BNIP3 family function, but kills through a BH3- and caspase-independent mechanism. The primary in vivo function in C. elegans is mitophagy rather than apoptosis regulation. This is an ancestral/secondary function.
worm	drp-1	IPR001401,IPR003130	GO:0003924	GTPase activity	ACCEPT	no		Duplicates the IBA annotation but via a different evidence pathway (InterPro domain mapping). Both are valid and consistent.
worm	dve-1	IPR039673	GO:0006338	chromatin remodeling	ACCEPT	no		This IEA annotation (from InterPro) is consistent with DVE-1's SATB-like domain structure and experimental evidence. DVE-1 associates with the NuRD chromatin remodeling complex (PMID:32789178) and cooperates with HDA-1 (PMID:32934238) to regulate chromatin state. Duplicate with IBA annotation above but both are acceptable given different evidence sources.
worm	eat-3	IPR001401	GO:0003924	GTPase activity	ACCEPT	no		The InterPro-based annotation correctly identifies GTPase activity based on the dynamin GTPase domain. This is a core function well-supported by the protein structure and mutant analysis.
worm	elt-2	IPR039355	GO:0003700	DNA-binding transcription factor activity	ACCEPT	no		Fundamental function of ELT-2 supported by extensive experimental evidence.
worm	elt-2	IPR000679,IPR013088	GO:0006355	regulation of DNA-templated transcription	ACCEPT	no		Accurate. ELT-2 is a transcriptional regulator controlling expression of intestinal genes.
worm	elt-2	IPR039355	GO:0006357	regulation of transcription by RNA polymerase II	ACCEPT	no		Accurate. ELT-2 is a transcription factor that regulates Pol II transcription.
worm	elt-2	IPR000679	GO:0043565	sequence-specific DNA binding	ACCEPT	no		Well-established that ELT-2 binds DNA in a sequence-specific manner (PMID:10518545, PMID:15733671).
worm	ent-1	IPR002259	GO:0005337	nucleoside transmembrane transporter activity	ACCEPT	no		Electronic annotation correctly identifies the molecular function, though less specific than the IBA annotation. Both are accurate and supported by experimental evidence.
worm	ent-1	IPR002259	GO:1901642	nucleoside transmembrane transport	ACCEPT	no		This is a more specific and accurate biological process term that better captures the transmembrane transport nature of ENT-1 function compared to the broader nucleoside transport term.
worm	fan-1	IPR011856	GO:0003676	nucleic acid binding	KEEP_AS_NON_CORE	yes		Correct but subsumed by more specific terms (GO:0003677, GO:0070336)
worm	fan-1	IPR006642	GO:0003677	DNA binding	KEEP_AS_NON_CORE	yes		Correct that FAN-1 binds DNA, but subsumed by more specific GO:0070336 (flap-structured DNA binding)
worm	fan-1	IPR033315	GO:0004518	nuclease activity	KEEP_AS_NON_CORE	yes		Correct but subsumed by more specific terms GO:0008409 and GO:0017108
worm	fan-1	IPR006642	GO:0006281	DNA repair	ACCEPT	no		Concordant with IMP experimental data
worm	fan-1	IPR014883	GO:0016788	hydrolase activity, acting on ester bonds	KEEP_AS_NON_CORE	yes		Correct but too general, subsumed by specific nuclease activity terms
worm	fan-1	IPR033315	GO:0036297	interstrand cross-link repair	ACCEPT	no		Core function, consistent with multiple lines of evidence
worm	fshr-1	IPR000276,IPR002131,IPR017452	GO:0016020	membrane	ACCEPT	no		Correct but less specific than the plasma membrane annotation. FSHR-1 is a membrane protein with seven transmembrane domains.
worm	fshr-1	IPR002131	GO:0016500	protein-hormone receptor activity	REMOVE	yes		There is no evidence that FSHR-1 functions as a hormone receptor in C. elegans. The ligand is unknown but appears to be related to infection/damage sensing rather than hormone signaling. C. elegans lacks vertebrate gonadotropins. The InterPro domain match reflects sequence similarity rather than functional conservation.
worm	fzo-1	IPR006884	GO:0008053	mitochondrial fusion	ACCEPT	no		Consistent with IBA and IMP annotations for the same term. The IEA evidence from InterPro domain analysis independently supports the fusion function. Multiple evidence codes for the same term are acceptable and reflect independent lines of evidence.
worm	fzo-1	IPR006884	GO:0016020	membrane	ACCEPT	no		While this is a very general term, it is technically correct. FZO-1 is an integral membrane protein with two transmembrane helices. The more specific annotation to mitochondrial outer membrane (GO:0005741) is also present. IEA annotations to general terms are acceptable when more specific terms are also annotated.
worm	gcn-2	IPR000719,IPR008271	GO:0004672	protein kinase activity	ACCEPT	no		Correct but generic. More specific term GO:0004694 (eIF2alpha kinase activity) is also annotated and is more informative.
worm	glh-1	IPR001878,IPR011545,IPR036875	GO:0003676	nucleic acid binding	ACCEPT	no		Correct but overly general. RNA binding and mRNA binding are more specific and informative. This is subsumed by more specific terms.
worm	glh-4	IPR001878,IPR011545,IPR036875	GO:0003676	nucleic acid binding	ACCEPT	no		GLH-4 has structural features for nucleic acid binding including CCHC zinc fingers and DEAD-box helicase domains. The term is accurate but general; more specific terms like RNA binding are also present.
worm	hlh-30	IPR011598,IPR036638	GO:0046983	protein dimerization activity	ACCEPT	no		Consistent with bHLH domain structure and experimentally demonstrated homodimerization.
worm	hsf-1	IPR000232	GO:0003700	DNA-binding transcription factor activity	ACCEPT	no		Consistent with IBA and IMP annotations for the same term. The InterPro HSF DNA-binding domain annotation accurately reflects HSF-1's function.
worm	hsf-1	IPR000232	GO:0006355	regulation of DNA-templated transcription	ACCEPT	no		Accurate annotation reflecting HSF-1's regulatory role in transcription. More specific child terms are also annotated with experimental evidence.
worm	hsp-1	IPR013126	GO:0016887	ATP hydrolysis activity	ACCEPT	no		ATP hydrolysis is the core enzymatic activity of HSP70 proteins, and this annotation is correct. While redundant with the IBA annotation, it independently confirms the same molecular function through domain-based inference.
worm	hsp-6	IPR012725	GO:0006457	protein folding	ACCEPT	no		Protein folding assistance is a core function of HSP70 chaperones. In the mitochondrial matrix, HSP-6 assists in folding of newly imported proteins and maintains proteostasis under stress conditions.
worm	hsp-6	IPR013126	GO:0016887	ATP hydrolysis activity	ACCEPT	no		Correct annotation. HSP70 proteins have intrinsic ATPase activity essential for their chaperone function. The ATPase_NBD domain (IPR043129) is present in HSP-6.
worm	hsp-6	IPR012725	GO:0051082	unfolded protein binding	MODIFY	yes	GO:0044183 protein folding chaperone	GO:0051082 is proposed for obsoletion. HSP-6 is a mitochondrial HSP70 foldase chaperone that binds unfolded clients and facilitates their folding in an ATP-dependent manner. The appropriate replacement term is GO:0044183 (protein folding chaperone).
worm	hsp-60	IPR018370	GO:0006457	protein folding	ACCEPT	no		Consistent with IBA annotation. The convergence of phylogenetic and domain-based evidence strengthens the annotation.
worm	hsp-60	IPR001844	GO:0042026	protein refolding	ACCEPT	no		"Protein refolding under stress conditions is a well-established function of HSP60 family chaperonins. UniProt states HSP-60 ""may also prevent misfolding and promote the refolding and proper assembly of unfolded polypeptides generated under stress conditions in the mitochondrial matrix."""
worm	hsp-60	IPR001844	GO:0140662	ATP-dependent protein folding chaperone	ACCEPT	no		This is an accurate and informative molecular function annotation for HSP-60. The chaperonin uses ATP binding and hydrolysis to drive conformational changes that facilitate protein folding in the chamber formed between the two heptameric rings.
worm	hsp-90	IPR001404	GO:0006457	protein folding	ACCEPT	no		Protein folding annotation based on HSP90 domain (IPR001404) is correct and consistent with experimental evidence.
worm	hsp-90	IPR001404	GO:0016887	ATP hydrolysis activity	ACCEPT	no		ATP hydrolysis is a defining feature of HSP90 proteins and is correctly inferred from domain architecture.
worm	hsp-90	IPR001404	GO:0051082	unfolded protein binding	MODIFY	yes	GO:0044183 protein folding chaperone	GO:0051082 is proposed for obsoletion. HSP-90 is an ATP-dependent foldase chaperone. The appropriate replacement term is GO:0044183 (protein folding chaperone). Consistent with MODIFY on IBA annotation.
worm	hsp-90	IPR001404	GO:0140662	ATP-dependent protein folding chaperone	ACCEPT	no		This accurately describes the core molecular function of HSP-90 as an ATP-dependent chaperone.
worm	ire-1	IPR045133	GO:0004521	RNA endonuclease activity	ACCEPT	no		Valid annotation via InterPro domain mapping. The KEN domain (IPR010513) and RNase_Ire1 (cd10422) domains support this function. Duplicates are acceptable when from different evidence sources.
worm	ire-1	IPR010513	GO:0004540	RNA nuclease activity	ACCEPT	no		Accurate general term for the RNase activity of IRE-1. The more specific child term GO:0004521 (RNA endonuclease activity) is also annotated and preferred.
worm	ire-1	IPR000719,IPR008271	GO:0004672	protein kinase activity	ACCEPT	no		Accurate annotation from InterPro domain mapping. The Pkinase domain (PF00069) is present. More specific child term for Ser/Thr kinase is also annotated.
worm	ire-1	IPR010513	GO:0006397	mRNA processing	ACCEPT	no		Valid annotation reflecting the mRNA splicing function. The term captures the processing of xbp-1 mRNA, though the more specific IRE1-mediated UPR term is preferred for capturing the biological context.
worm	ire-1	IPR045133	GO:0030968	endoplasmic reticulum unfolded protein response	ACCEPT	no		Core biological process annotation. IRE-1 is a major and highly conserved ER stress sensor that activates the UPR. The child term GO:0036498 (IRE1-mediated UPR) is more specific.
worm	lbp-8	IPR000463,IPR031259	GO:0008289	lipid binding	ACCEPT	no		The IEA annotation is correct but broader than the more specific fatty acid binding annotations already present. It is acceptable as an independent InterPro-based prediction. LBP-8 binds diverse lipids including fatty acids and OEA (PMID:25554789, PMID:31292465).
worm	lipl-4	IPR006693	GO:0006629	lipid metabolic process	ACCEPT	no		This IEA annotation is correct and redundant with the IBA annotation. The InterPro domain-based inference is sound given the established lipase function of LIPL-4. Duplicates with different evidence codes are acceptable.
worm	lipl-4	IPR025483	GO:0016788	hydrolase activity, acting on ester bonds	ACCEPT	no		This is a correct but general parent term of the more specific triacylglycerol lipase activity. The IEA mapping from the eukaryotic lipase InterPro domain is appropriate. While broader than other MF annotations, it is not incorrect and reflects the domain-level inference.
worm	lys-7	IPR002053	GO:0003796	lysozyme activity	MARK_AS_OVER_ANNOTATED	yes		"The protein contains a lysozyme domain but UniProt cautions that ""Lacks conserved active site residues, suggesting it has no catalytic activity."" No experimental evidence demonstrates that LYS-7 has lysozyme catalytic activity. The protein may function through a non-enzymatic mechanism."
worm	lys-7	IPR002053	GO:0009253	peptidoglycan catabolic process	MARK_AS_OVER_ANNOTATED	yes		"While typical lysozymes degrade peptidoglycan, the UniProt record notes that LYS-7 ""Lacks conserved active site residues, suggesting it has no catalytic activity."" Without experimental evidence of peptidoglycan degradation activity, this annotation is likely an over-annotation based on family membership rather than demonstrated function."
worm	lys-7	IPR002053	GO:0016998	cell wall macromolecule catabolic process	MARK_AS_OVER_ANNOTATED	yes		As LYS-7 lacks conserved catalytic residues and may not have enzymatic activity, assigning cell wall degradation activity is likely an over-annotation based on domain homology rather than demonstrated function.
worm	mbk-2	IPR000719,IPR008271	GO:0004672	protein kinase activity	ACCEPT	no		Accurate parent term derived from InterPro domain annotation. More specific child terms (protein serine/threonine kinase activity, protein tyrosine kinase activity) are also annotated with experimental evidence.
worm	mcm-4	IPR001208,IPR008047,IPR018525,IPR031327	GO:0003677	DNA binding	ACCEPT	no		DNA binding is a general, correct parent term for the MCM helicase. The more specific single-stranded DNA binding annotation is also present; the broader IEA is acceptable.
worm	mcm-4	IPR001208,IPR008047,IPR018525,IPR031327	GO:0005524	ATP binding	ACCEPT	no		Direct consequence of the conserved AAA+ ATPase domain; ATP binding is a standard, well-supported molecular function for MCM subunits.
worm	mcm-4	IPR018525	GO:0006260	DNA replication	ACCEPT	no		Central, well-established function; mcm-4 mutants fail postembryonic DNA synthesis.
worm	mcm-4	IPR008047	GO:0006270	DNA replication initiation	ACCEPT	no		Correct process annotation for an MCM subunit acting in origin licensing and initiation.
worm	mcm-4	IPR008047	GO:0042555	MCM complex	ACCEPT	no		Correct core localization; redundant with the experimentally and phylogenetically supported MCM complex annotations.
worm	met-2	IPR001739,IPR016177	GO:0003677	DNA binding	MARK_AS_OVER_ANNOTATED	yes		The IEA annotation based on InterPro MBD domain is technically accurate as MET-2 contains an MBD domain (IPR001739), but DNA binding is not the primary or core function. MET-2 functions as a histone methyltransferase and its chromatin targeting involves protein-protein interactions with LIN-65 and ARLE-14 rather than direct DNA binding.
worm	met-2	IPR007728	GO:0008270	zinc ion binding	ACCEPT	no		Zinc binding is structurally important for SET domain-containing methyltransferases and is well-documented for MET-2 based on domain architecture.
worm	met-2	IPR007728	GO:0042054	histone methyltransferase activity	ACCEPT	no		Accurate annotation based on domain architecture. MET-2 contains SET, pre-SET, and post-SET domains characteristic of histone methyltransferases.
worm	mex-5	IPR045877	GO:0003729	mRNA binding	ACCEPT	no		This is a well-supported annotation. MEX-5 binds mRNA with high affinity through its tandem CCCH zinc fingers.
worm	miro-1	IPR001806,IPR020860,IPR021181	GO:0003924	GTPase activity	ACCEPT	no		Same as IBA annotation. Multiple evidence sources for core GTPase activity are appropriate. InterPro-based inference is consistent with the phylogenetic evidence.
worm	miro-1	IPR002048,IPR021181	GO:0005509	calcium ion binding	ACCEPT	no		Calcium binding through EF-hands is a core molecular function that enables calcium-dependent regulation of mitochondrial transport. Essential for the calcium-sensing function of Miro proteins.
worm	miro-1	IPR021181	GO:0007005	mitochondrion organization	ACCEPT	no		Same process as IBA annotation. Multiple evidence sources support this biological process role.
worm	mks-3	IPR019170	GO:0036038	MKS complex	ACCEPT	no		This IEA annotation from InterPro is well-supported. MKS-3 contains the Meckelin domain (IPR019170/Pfam:PF09773) which is a defining feature of this protein family. Experimental evidence confirms MKS-3 functions within the MKS module and genetically interacts with other module components.
worm	mks-3	IPR019170	GO:0060271	cilium assembly	ACCEPT	no		While this duplicates the IBA annotation for cilium assembly, it is appropriate to retain both as they derive from independent evidence sources (InterPro domain mapping vs. phylogenetic inference). Both correctly capture the role of MKS-3 in ciliogenesis.
worm	nhr-49	IPR049636	GO:0000978	RNA polymerase II cis-regulatory region sequence-specific DNA binding	ACCEPT	no		The InterPro-based IEA annotation is consistent with NHR-49 domain architecture and its demonstrated function as a transcription factor. It is broader than the IBA annotation for the same term, but both are acceptable annotations for the same GO term from different evidence sources.
worm	nhr-49	IPR001628	GO:0003700	DNA-binding transcription factor activity	ACCEPT	no		While GO:0004879 (nuclear receptor activity) is more specific and already annotated, this broader IEA annotation from InterPro is not incorrect. It is acceptable to retain both a broader IEA and a more specific IBA annotation for the same gene.
worm	nhr-49	IPR001628,IPR013088	GO:0006355	regulation of DNA-templated transcription	ACCEPT	no		The annotation is correct. While it is broader than the IBA annotation for Pol II-specific regulation, it is not incorrect to retain both. NHR-49 is fundamentally a transcriptional regulator.
worm	nhr-49	IPR001628,IPR013088	GO:0008270	zinc ion binding	ACCEPT	no		The zinc ion binding annotation is correct based on the well-characterized C4-type zinc finger motifs in the NHR-49 DNA-binding domain. This is a structural feature inherent to all nuclear hormone receptors.
worm	nhr-49	IPR001628	GO:0043565	sequence-specific DNA binding	ACCEPT	no		The annotation is correct. NHR-49 binds DNA in a sequence-specific manner through its zinc finger DNA-binding domain. While more specific annotations exist, the IEA from InterPro is not incorrect.
worm	nhr-80	IPR049636	GO:0000978	RNA polymerase II cis-regulatory region sequence-specific DNA binding	ACCEPT	no		NHR-80 is a nuclear hormone receptor with a conserved zinc-finger DNA-binding domain (HNF4-like). It regulates transcription of specific target genes including delta-9 desaturases, consistent with cis-regulatory region binding. The IEA annotation from InterPro domain mapping is appropriate for this NHR family member.
worm	nhr-80	IPR001628	GO:0003700	DNA-binding transcription factor activity	MODIFY	yes	GO:0098531 ligand-modulated transcription factor activity; GO:0004879 nuclear receptor activity	While the annotation is correct, NHR-80 is specifically a ligand-activated nuclear receptor that binds oleoylethanolamide (OEA) with Kd ~7.8 uM (PMID:25554789). A more specific term would be more informative. GO:0098531 (ligand-activated transcription factor activity) or GO:0004879 (nuclear receptor activity) would better capture the molecular function.
worm	nhr-80	IPR001628,IPR013088	GO:0006355	regulation of DNA-templated transcription	ACCEPT	no		This is a broadly correct IEA annotation. NHR-80 is a transcription factor that regulates DNA-templated transcription. While more specific terms exist (positive regulation of transcription by RNA polymerase II is also annotated), this general term from InterPro mapping is not wrong and captures the core transcriptional regulatory function.
worm	nhr-80	IPR001628,IPR013088	GO:0008270	zinc ion binding	ACCEPT	no		NHR-80 has two NR C4-type zinc finger motifs in its DNA-binding domain that require zinc ion coordination for proper folding and DNA binding. This is a standard structural feature of all nuclear hormone receptors and is well supported by sequence analysis.
worm	nhr-80	IPR001628	GO:0043565	sequence-specific DNA binding	ACCEPT	no		Appropriate IEA annotation based on the conserved nuclear receptor DNA-binding domain. NHR-80 clearly binds specific regulatory elements to control target gene expression, as demonstrated by its selective regulation of fat-5, fat-6, fat-7 and other target genes.
worm	nipi-3	IPR000719	GO:0004672	protein kinase activity	REMOVE	yes		This annotation is incorrect. NIPI-3 is a well-characterized pseudokinase that lacks key catalytic residues and is not expected to have protein kinase activity. UniProt explicitly states the protein kinase domain is predicted to be catalytically inactive (PROSITE-ProRule:PRU00159). PMID:27927209 confirms this. The IEA annotation based solely on domain presence is misleading for this pseudokinase.
worm	nphp-4	IPR029775	GO:0005856	cytoskeleton	MARK_AS_OVER_ANNOTATED	yes		While technically not wrong (cilia are cytoskeletal structures), this is too broad and uninformative. The more specific ciliary component annotations are preferred.
worm	nphp-4	IPR029775	GO:0090090	negative regulation of canonical Wnt signaling pathway	KEEP_AS_NON_CORE	yes		Duplicate annotation by different method. The Wnt signaling role is likely secondary to core ciliary gating function.
worm	nphp-4	IPR029775	GO:0097730	non-motile cilium	ACCEPT	no		Valid broader annotation consistent with more specific experimental evidence.
worm	nsy-1	IPR043969	GO:0000165	MAPK cascade	ACCEPT	no		This broader term is correctly applied based on domain annotation. NSY-1 is indeed a MAP3K functioning in MAPK signaling. While more specific terms exist (p38MAPK cascade), this IEA annotation is not incorrect.
worm	nsy-1	IPR000719,IPR008271	GO:0004672	protein kinase activity	ACCEPT	no		Duplicate of IBA annotation - both are valid. The IEA provides independent support from domain analysis. Protein kinase activity is a core molecular function of NSY-1.
worm	ocr-2	IPR005821,IPR024862	GO:0005216	monoatomic ion channel activity	ACCEPT	no		IEA based on InterPro domain annotation is correct but very general. The ion transport domain (Pfam PF00520) is present from residues 517-771 per UniProt. While redundant with calcium channel activity, this broad term is not incorrect.
worm	ocr-2	IPR005821,IPR024862	GO:0016020	membrane	ACCEPT	no		While overly general, this is not incorrect. OCR-2 is a multi-pass membrane protein with transmembrane helices at positions 426-445, 517-538, 550-573, 585-606, 613-630, 636-654, and 738-760 per UniProt.
worm	ocr-2	IPR005821	GO:0055085	transmembrane transport	ACCEPT	no		While overly general, this is not incorrect for a transmembrane channel protein. More specific annotations exist.
worm	osm-3	IPR001752	GO:0008017	microtubule binding	ACCEPT	no		Correct annotation, duplicates IBA with different evidence code (InterPro).
worm	pef-1	IPR012008	GO:0004721	phosphoprotein phosphatase activity	ACCEPT	no		This broader term is consistent with the protein's function and is appropriately inferred from domain architecture. The IEA annotation is valid alongside the more specific IBA annotation for GO:0004722.
worm	pef-1	IPR012008	GO:0005506	iron ion binding	REMOVE	yes		This is likely an incorrect inference. PPEF family phosphatases use manganese as the catalytic metal ion. UniProt annotation and experimental evidence from related proteins indicate manganese binding, not iron. The InterPro inference may be overly broad.
worm	pef-1	IPR002048,IPR012008	GO:0005509	calcium ion binding	ACCEPT	no		Calcium binding is a defining feature of the PPEF family and has been experimentally verified for CePPEF. The EF-hand domains (residues 546-581, 629-664, 669-704) bind 1-2 calcium ions per protein.
worm	pef-1	IPR012008	GO:0030145	manganese ion binding	ACCEPT	no		Manganese binding is essential for phosphatase catalytic activity and is well-supported by domain architecture and similarity to characterized PPP phosphatases. The metallophos domain contains conserved manganese-binding residues.
worm	pef-1	IPR012008	GO:0050906	detection of stimulus involved in sensory perception	MODIFY	yes	GO:0040040 thermosensory behavior; GO:0050906 detection of stimulus involved in sensory perception	While PEF-1 is involved in sensory processes, it is not a receptor that directly detects stimuli. Rather, it modulates sensory signaling in cilia. More specific behavioral or regulatory terms would be more accurate.
worm	pek-1	IPR000719,IPR008271	GO:0004672	protein kinase activity	ACCEPT	no		This is a correct parent term annotation. While less specific than GO:0004694 (eIF2alpha kinase activity), it accurately reflects PEK-1's function. The IEA annotation from InterPro correctly identifies the protein kinase domain.
worm	pink-1	IPR000719	GO:0004672	protein kinase activity	ACCEPT	no		Correct annotation based on the presence of the protein kinase domain. While GO:0004674 (protein serine/threonine kinase activity) is more specific and also annotated, this parent term is acceptable as a complementary IEA annotation.
worm	pkd-2	IPR003915	GO:0005509	calcium ion binding	ACCEPT	no		Reasonable IEA annotation based on domain composition. The PKD2 domain includes calcium-binding capabilities that are important for channel regulation. This is consistent with PKD-2's role as a calcium channel.
worm	pkd-2	IPR003915	GO:0016020	membrane	ACCEPT	no		Duplicate of IBA annotation above. Both appropriately capture membrane localization based on different evidence sources (InterPro and phylogenetic inference).
worm	pmk-1	IPR000719	GO:0004672	protein kinase activity	ACCEPT	no		Accurate parent term annotation. PMK-1 has well-established protein kinase activity confirmed by IDA evidence.
worm	prg-1	IPR003165,IPR036397	GO:0003676	nucleic acid binding	MARK_AS_OVER_ANNOTATED	yes		While technically correct, this term is too general to be informative. More specific annotations such as piRNA binding (GO:0034584) and 21U-RNA binding (GO:0034583) better capture PRG-1's molecular function.
worm	sek-1	IPR000719,IPR008271	GO:0004672	protein kinase activity	ACCEPT	no		Accurate parent term for the more specific MAP kinase kinase activity.
worm	sir-2.1	IPR003000	GO:0070403	NAD+ binding	ACCEPT	no		NAD+ is the essential cofactor for sirtuin catalytic activity. The UniProt record documents NAD binding sites (residues 153-172, 237-240, 327-329, 352-354, 369). This is a core molecular function.
worm	skn-1	IPR047167	GO:0000978	RNA polymerase II cis-regulatory region sequence-specific DNA binding	ACCEPT	no		InterPro-based annotation is accurate given SKN-1's characterized DNA-binding domain and experimental validation of sequence-specific binding through crystal structure analysis.
worm	skn-1	IPR004827,IPR047167	GO:0003700	DNA-binding transcription factor activity	ACCEPT	no		Accurate annotation consistent with SKN-1's established function as a transcription factor.
worm	skn-1	IPR004826,IPR004827,IPR008917	GO:0006355	regulation of DNA-templated transcription	ACCEPT	no		Accurate annotation. SKN-1 regulates transcription of stress response and developmental genes.
worm	skn-1	IPR047167	GO:0006357	regulation of transcription by RNA polymerase II	ACCEPT	no		Accurate annotation consistent with SKN-1's established function in RNA polymerase II-dependent transcription.
worm	spg-7	IPR000642,IPR005936,IPR011546,IPR037219	GO:0004176	ATP-dependent peptidase activity	ACCEPT	no		This term accurately describes SPG-7's integrated molecular function combining ATPase and peptidase activities. The InterPro-based IEA annotation is well-supported by domain architecture.
worm	spg-7	IPR000642,IPR005936,IPR011546,IPR037219	GO:0004222	metalloendopeptidase activity	ACCEPT	no		Both the IEA (InterPro) and IBA (PAINT) annotations support this core molecular function. Keeping both evidence types is appropriate as they represent independent lines of evidence.
worm	spg-7	IPR011546	GO:0008270	zinc ion binding	ACCEPT	no		Correct annotation. Zinc binding is essential for SPG-7's metallopeptidase activity. The zinc ion is required for catalysis at the active site.
worm	spg-7	IPR005936,IPR011546	GO:0016020	membrane	ACCEPT	no		Not incorrect but very general. The more specific term GO:0005743 (mitochondrial inner membrane) is also annotated, which provides better precision.
worm	spg-7	IPR003959,IPR003960	GO:0016887	ATP hydrolysis activity	ACCEPT	no		Core molecular function. ATP hydrolysis drives the mechanical work of unfolding substrates and translocating them into the proteolytic chamber.
worm	sta-2	IPR001217,IPR008967	GO:0003700	DNA-binding transcription factor activity	ACCEPT	no		Appropriate annotation based on domain architecture and functional evidence.
worm	sta-2	IPR001217,IPR008967	GO:0006355	regulation of DNA-templated transcription	ACCEPT	no		Appropriate annotation for a STAT transcription factor.
worm	sta-2	IPR001217	GO:0007165	signal transduction	ACCEPT	no		STA-2 participates in signal transduction pathways that transmit infection and damage signals to the nucleus.
worm	tir-1	IPR000157	GO:0007165	signal transduction	ACCEPT	no		Correct but general annotation. TIR-1 clearly functions in signal transduction as an adaptor protein activating MAPK cascades.
worm	tir-1	IPR039184	GO:0034128	negative regulation of MyD88-independent toll-like receptor signaling pathway	REMOVE	yes		This annotation is based on mammalian SARM1 function but may not apply to C. elegans TIR-1. The nematode TIR-1 functions in a TLR-independent manner. PMID:15048112 explicitly states TIR-1 activity is independent of the single nematode Toll-like receptor.
worm	tir-1	IPR039184	GO:0035591	signaling adaptor activity	ACCEPT	no		Correct annotation also supported by IDA evidence from PMID:15625192.
worm	ufd-1	IPR004854	GO:0006511	ubiquitin-dependent protein catabolic process	ACCEPT	no		This annotation accurately reflects UFD-1's role in promoting proteasomal degradation of ubiquitinated substrates. The CDC-48/UFD-1/NPL-4 complex extracts ubiquitinated proteins and delivers them to the proteasome.
worm	unc-1	IPR001972	GO:0016020	membrane	KEEP_AS_NON_CORE	yes		This IEA annotation based on InterPro domain prediction is accurate but extremely general. UNC-1 is a multi-pass membrane protein, but the more informative localizations are plasma membrane and gap junction. Keep as non-core background annotation.
worm	wago-1	IPR003165,IPR036397	GO:0003676	nucleic acid binding	ACCEPT	no		This is a valid but very general annotation based on domain composition. The PAZ and Piwi domains are nucleic acid binding domains. More specific annotations (RNA binding, siRNA binding) are also present and more informative.
worm	wago-1	IPR003100	GO:0003723	RNA binding	ACCEPT	no		WAGO-1 binds 22G-RNAs through its PAZ and Piwi domains. RNA binding is a core molecular function. This annotation is appropriate as a broader classification of the siRNA binding activity.
worm	xbp-1	IPR004827,IPR046347	GO:0003700	DNA-binding transcription factor activity	ACCEPT	no		Correct but less specific than GO:0000981. The annotation accurately reflects XBP-1's function as a transcription factor, supported by the bZIP domain (IPR004827) and ER stress-regulated TF family (IPR052470).
worm	xbp-1	IPR004827,IPR046347	GO:0006355	regulation of DNA-templated transcription	ACCEPT	no		Correct annotation. XBP-1s is a transcriptional activator that regulates expression of UPR target genes. This is well-established from genetic studies showing XBP-1 is required for induction of hsp-3, hsp-4, and other ER stress genes (PMID:11779465, PMID:16184190).
worm	zip-2	IPR004827,IPR031106,IPR046347	GO:0003700	DNA-binding transcription factor activity	MARK_AS_OVER_ANNOTATED	yes		Correct but too general. GO:0000981 (DNA-binding transcription factor activity, RNA polymerase II-specific) provides more specificity and is already annotated via IBA.
worm	zip-2	IPR004827,IPR046347	GO:0006355	regulation of DNA-templated transcription	MARK_AS_OVER_ANNOTATED	yes		Correct but too general. More specific annotations to GO:0006357 (IBA) and GO:0045944 (IMP) are already present and provide more information about ZIP-2's transcriptional function.
worm	znfx-1	IPR000967	GO:0005634	nucleus	REMOVE	yes		"Experimental evidence from multiple publications demonstrates cytoplasmic localization to Z granules and perinuclear region, not nuclear localization. UniProt subcellular location explicitly lists ""Cytoplasm, perinuclear region"" and ""Cytoplasmic granule"" with no nuclear localization."
yeast	APJ1	IPR008971,IPR044713	GO:0006457	protein folding	ACCEPT	no		Retained as supported or plausible for this gene and evidence context.
yeast	APJ1	IPR044713	GO:0030544	Hsp70 protein binding	ACCEPT	no		Retained as supported or plausible for this gene and evidence context.
yeast	APJ1	IPR001305	GO:0031072	heat shock protein binding	ACCEPT	no		Retained as supported or plausible for this gene and evidence context.
yeast	APJ1	IPR001305,IPR008971	GO:0051082	unfolded protein binding	MODIFY	yes	GO:0044183 protein folding chaperone	Modified to align with current curation guidance and improve term specificity.
yeast	ASF1	IPR017282	GO:0006334	nucleosome assembly	ACCEPT	no		IEA evidence is appropriate. Nucleosome assembly is documented core function supported by multiple experimental studies (nucleosome assembly with CAF-1, HIRA complexes).
yeast	ASF1	IPR017282	GO:0006337	nucleosome disassembly	ACCEPT	no		IEA is supported by experimental evidence (PMID:16678113 - IMP annotation showing ASF1 mediates histone eviction during RNA polymerase II elongation).
yeast	ASF1	IPR017282	GO:0042393	histone binding	ACCEPT	no		IEA annotation is consistent with strong IBA evidence and experimental validation. Histone H3-H4 dimer binding is ASF1's defining function and is a core annotation across all evidence types.
yeast	ATG7	IPR035985	GO:0008641	ubiquitin-like modifier activating enzyme activity	ACCEPT	no		Accepted because this annotation aligns with established ATG7 E1-like function and autophagy pathway roles.
yeast	ATP11	IPR010591	GO:0065003	protein-containing complex assembly	MODIFY	yes	GO:0033615 mitochondrial proton-transporting ATP synthase complex assembly	Replace with the specific mitochondrial ATP synthase assembly term.
yeast	CAF1	IPR036397	GO:0003676	nucleic acid binding	MARK_AS_OVER_ANNOTATED	yes		More specific RNA binding and poly(A)-specific ribonuclease activities capture the functional role.
yeast	CAF1	IPR039637	GO:0030014	CCR4-NOT complex	ACCEPT	no		CAF1/Pop2p is consistently identified within CCR4-NOT complex purifications.
yeast	CCT2	IPR012716	GO:0005829	cytosol	ACCEPT	no		Retain as the more precise core localization for cytosolic CCT/TRiC.
yeast	CCT2	IPR002194,IPR012716	GO:0016887	ATP hydrolysis activity	ACCEPT	no		Retain as the ATPase activity coupled to the CCT/TRiC folding cycle.
yeast	CCT2	IPR017998	GO:0140662	ATP-dependent protein folding chaperone	ACCEPT	no		Retain as the best complex-level molecular-function annotation for Cct2-containing CCT/TRiC.
yeast	CCT3	IPR002194,IPR012719	GO:0016887	ATP hydrolysis activity	ACCEPT	no		ATP hydrolysis is a defensible subunit-level molecular function for CCT family members and is directly tied to the chaperonin folding cycle.
yeast	CCT3	IPR017998	GO:0140662	ATP-dependent protein folding chaperone	ACCEPT	no		The term is appropriate as a complex-level chaperonin function; in the synthesized core function it is modeled as a contributed-to molecular function rather than a standalone activity of an isolated subunit.
yeast	CCT4	IPR002194,IPR012717	GO:0016887	ATP hydrolysis activity	ACCEPT	no		CCT is an ATP-dependent folding machine and the InterPro/PANTHER family supports the conserved chaperonin ATPase fold.
yeast	CCT4	IPR017998	GO:0140662	ATP-dependent protein folding chaperone	ACCEPT	no		CCT/TRiC is an ATP-dependent folding machine, and CCT4 contributes as one subunit of this complex.
yeast	CCT5	IPR002194	GO:0016887	ATP hydrolysis activity	ACCEPT	no		ATP hydrolysis is a defensible subunit-level molecular function for CCT family members and is directly tied to the chaperonin folding cycle.
yeast	CCT5	IPR017998	GO:0140662	ATP-dependent protein folding chaperone	ACCEPT	no		The term is appropriate as a complex-level chaperonin function; in the synthesized core function it is modeled as a contributed-to molecular function rather than a standalone activity of an isolated subunit.
yeast	CCT6	IPR002194,IPR012722	GO:0016887	ATP hydrolysis activity	ACCEPT	no		ATP hydrolysis is a defensible subunit-level molecular function for CCT family members and is directly tied to the chaperonin folding cycle.
yeast	CCT6	IPR017998	GO:0140662	ATP-dependent protein folding chaperone	ACCEPT	no		The term is appropriate as a complex-level chaperonin function; in the synthesized core function it is modeled as a contributed-to molecular function rather than a standalone activity of an isolated subunit.
yeast	CCT7	IPR002194,IPR012720	GO:0016887	ATP hydrolysis activity	ACCEPT	no		ATP hydrolysis drives the CCT/TRiC conformational cycle for client folding.
yeast	CCT7	IPR017998	GO:0140662	ATP-dependent protein folding chaperone	ACCEPT	no		CCT7 contributes to ATP-dependent protein folding chaperone activity as a complex subunit.
yeast	CCT8	IPR002194,IPR012721	GO:0016887	ATP hydrolysis activity	ACCEPT	no		The InterPro/PANTHER chaperonin family supports the conserved ATPase fold used during CCT-mediated substrate folding.
yeast	CCT8	IPR017998	GO:0140662	ATP-dependent protein folding chaperone	ACCEPT	no		CCT/TRiC is an ATP-dependent folding machine, and CCT8 is a core subunit of that complex.
yeast	CDC37	IPR013855	GO:0019901	protein kinase binding	ACCEPT	no		Cdc37 is a kinase-targeting co-chaperone, and protein kinase binding is the most informative currently annotated molecular function for its client specificity.
yeast	CNE1	IPR001580,IPR009033,IPR018124	GO:0005509	calcium ion binding	REMOVE	yes		The direct yeast study contradicts the inferred calcium-binding annotation; calnexin-family membership alone is insufficient evidence for this molecular function in Cne1p.
yeast	CNE1	IPR001580	GO:0005783	endoplasmic reticulum	ACCEPT	no		Direct localization and membrane-association evidence places Cne1p in the ER membrane/ER quality-control compartment.
yeast	CNE1	IPR001580	GO:0006457	protein folding	ACCEPT	no		Direct yeast evidence supports Cne1p in ER folding/quality control and retention/elimination of misfolded proteins.
yeast	CNE1	IPR001580	GO:0051082	unfolded protein binding	MODIFY	yes	GO:0044183 protein folding chaperone	Replace with protein folding chaperone, while separately capturing oligosaccharide/lectin binding in core function and proposed terminology.
yeast	COX20	IPR022533	GO:0033617	mitochondrial respiratory chain complex IV assembly	ACCEPT	no		The Cox20 domain family is specific to cytochrome c oxidase assembly factors and is supported by yeast experimental evidence.
yeast	CPR6	IPR020892	GO:0006457	protein folding	ACCEPT	no		Consistent with IBA and experimental annotations for protein folding involvement.
yeast	CPR7	IPR020892	GO:0006457	protein folding	ACCEPT	no		Retain as the biological process supported by Cpr7 PPIase and Hsp90 co-chaperone functions.
yeast	CRH1	IPR000757	GO:0004553	hydrolase activity, hydrolyzing O-glycosyl compounds	KEEP_AS_NON_CORE	yes		Technically correct -- CRH1 has documented weak endochitinase activity (PMID:23919454) -- but the primary evolved function is transglycosylation, not hydrolysis. This InterPro-based annotation reflects the ancestral GH16 hydrolase function rather than the derived transglycosylase specialization.
yeast	CRH1	IPR000757	GO:0005975	carbohydrate metabolic process	KEEP_AS_NON_CORE	yes		Correct but very broad. Subsumed by the more specific GO:0006030 (chitin metabolic process) which is already annotated with experimental evidence.
yeast	CRH1	IPR017168	GO:0016798	hydrolase activity, acting on glycosyl bonds	KEEP_AS_NON_CORE	yes		Correct but broad and redundant. The more specific endochitinase activity (GO:0008843) is already annotated. The primary function is transglycosylase, not hydrolase.
yeast	CRH1	IPR017168	GO:0071555	cell wall organization	KEEP_AS_NON_CORE	yes		Correct but subsumed by the more specific GO:0031505 (fungal-type cell wall organization) which is already annotated.
yeast	CYC1	IPR002327,IPR009056,IPR036909	GO:0020037	heme binding	ACCEPT	no		IEA annotation based on InterPro domain membership correctly identifies heme binding as a molecular function of CYC1. UniProt explicitly states CYC1 binds 1 heme c group covalently per subunit, with covalent binding at His-18 and His-81 and axial iron coordination by His-86 and Met-80. This molecular function is fundamental to the redox chemistry enabling electron transfer. IEA from protein family annotation is appropriate for this well-characterized feature.
yeast	DBP5	IPR011545	GO:0003676	nucleic acid binding	KEEP_AS_NON_CORE	yes		This is a parent term of RNA binding and is appropriate but redundant with more specific annotations. RNA binding subsumes this annotation.
yeast	DEG1	IPR001406,IPR020097,IPR020103	GO:0001522	pseudouridine synthesis	MARK_AS_OVER_ANNOTATED	yes	GO:0031119 tRNA pseudouridine synthesis; GO:1990481 mRNA pseudouridine synthesis	While technically correct, this general biological process term lacks specificity. DEG1/Pus3p specifically catalyzes pseudouridine formation in tRNA at positions 38/39 and in specific mRNAs, not general pseudouridine synthesis.
yeast	DEG1	IPR001406,IPR020094,IPR020095,IPR020097,IPR020103	GO:0003723	RNA binding	MARK_AS_OVER_ANNOTATED	yes		RNA binding is an implicit requirement for any RNA-modifying enzyme and provides no specific functional information. The specific catalytic activities (tRNA pseudouridine(38/39) synthase activity) already imply RNA binding capability. This term adds no value to understanding DEG1's function.
yeast	DEG1	IPR001406,IPR020097,IPR020103	GO:0009451	RNA modification	MARK_AS_OVER_ANNOTATED	yes	GO:0031119 tRNA pseudouridine synthesis; GO:1990481 mRNA pseudouridine synthesis	RNA modification is too broad a category. DEG1 specifically performs pseudouridylation of tRNA and mRNA, not general RNA modifications like methylation or acetylation.
yeast	DEG1	IPR001406,IPR020094,IPR020095,IPR020097,IPR020103	GO:0009982	pseudouridine synthase activity	ACCEPT	no		Retain this term because it is the best available MF to represent DEG1/Pus3p's pseudouridine synthase activity beyond tRNA (mRNA pseudouridylation). Replacing it with the tRNA-specific term would lose coverage of the non-tRNA substrate activity.
yeast	DOT1	IPR021162	GO:0000077	DNA damage checkpoint signaling	ACCEPT	no		While the annotation is correct, it is a computational inference from InterPro domain annotation rather than direct evidence. The experimental evidence (IBA and IMP) for this function is superior and this IEA annotation is superseded by stronger evidence.
yeast	DOT1	IPR021162	GO:0000786	nucleosome	ACCEPT	no		This annotation correctly reflects DOT1's essential interaction with nucleosomes. DOT1 has essentially no activity on free histone H3, requiring the nucleosomal context for both binding and catalytic activity.
yeast	DOT1	IPR021162	GO:0006281	DNA repair	ACCEPT	no		Redundant with the IBA GO:0006281 annotation. Both are correct and provide complementary evidence. InterPro domain-based inference provides additional computational support.
yeast	DOT1	IPR021162,IPR025789,IPR030445	GO:0031151	histone H3K79 methyltransferase activity	ACCEPT	no		This is the most specific and informative molecular function annotation. InterPro domain signatures correctly predict this activity. Redundant with IBA and IDA annotations but all three levels of evidence support this core function.
yeast	DOT1	IPR021162	GO:0031509	subtelomeric heterochromatin formation	ACCEPT	no		Redundant with IBA and IMP annotations for the same term. All provide complementary evidence from different sources. InterPro domain-based inference provides additional computational support.
yeast	DOT1	IPR021162	GO:0042393	histone binding	ACCEPT	no		DOT1 forms extensive contacts with histones during nucleosome binding and catalysis, particularly with the histone H4 tail basic patch region. This annotation correctly describes a required molecular interaction for enzyme function. Falcon deep research provides quantitative nucleosome-binding affinities (Kd ~70-83 nM) consistent with direct, stable histone/nucleosome engagement.
yeast	DOT1	IPR030445	GO:0051726	regulation of cell cycle	KEEP_AS_NON_CORE	yes		While DOT1 does affect cell cycle through its checkpoint functions, calling this 'regulation of cell cycle' is misleading. DOT1 specifically regulates checkpoint control (GO:0000077, GO:0031571, GO:0031573) not the cell cycle per se. The checkpoint terms are more precise.
yeast	EGD2	IPR016641	GO:0005854	nascent polypeptide-associated complex	ACCEPT	no		InterPro and primary literature identify EGD2 as the alpha-NAC subunit in yeast.
yeast	ERG19	IPR029765	GO:0005829	cytosol	ACCEPT	no		Redundant with the IBA and HDA cytosol/cytoplasm annotations but correct; MDD is a cytosolic enzyme.
yeast	ERG19	IPR005935	GO:0008299	isoprenoid biosynthetic process	ACCEPT	no		This is a true high-level parent of the enzyme's specific role (IPP biosynthesis via the mevalonate pathway). An IEA annotation broader than the IBA/experimental terms is acceptable here and provides useful pathway context.
yeast	ERG19	IPR005935	GO:0016831	carboxy-lyase activity	MODIFY	yes	GO:0004163 diphosphomevalonate decarboxylase activity	GO:0016831 is a direct parent of diphosphomevalonate decarboxylase activity and is uninformatively general for a single-function enzyme whose specific activity is well established. Replace with the specific child term, which is already present with experimental (IDA/IMP) support.
yeast	ESA1	IPR002717	GO:0006355	regulation of DNA-templated transcription	ACCEPT	no		This annotation correctly distinguishes ESA1's regulatory role from core transcription machinery. IEA from InterPro domain analysis is appropriate.
yeast	GCN5	IPR037800	GO:0004402	histone acetyltransferase activity	ACCEPT	no		The presence of the IPR037800 GCN5 domain ensures histone acetyltransferase activity. The broader GO:0004402 HAT activity term is appropriately inferred from domain annotation. Well-supported by crystal structures (PDB:1YGH, 1E6I, 6CW2, 6CW3) demonstrating catalytic mechanism.
yeast	GCN5	IPR000182	GO:0016747	acyltransferase activity, transferring groups other than amino-acyl groups	ACCEPT	no		This term precisely describes GCN5 catalytic function: transfer of acetyl groups (not amino-acyl groups) to target proteins. The GNAT domain (InterPro:IPR000182) is the defining feature. This annotation is accurate and specific.
yeast	GET3	IPR016300,IPR027542	GO:0016887	ATP hydrolysis activity	ACCEPT	no		Retained as supported or plausible for this gene and evidence context.
yeast	HAP4	IPR018287	GO:0006355	regulation of DNA-templated transcription	ACCEPT	no		This is a mechanistically accurate annotation for a transcriptional regulator/activator. The IEA evidence based on InterPro domain mapping is reasonable for transcription factor domains.
yeast	HSC82	IPR001404	GO:0140662	ATP-dependent protein folding chaperone	ACCEPT	no		GO:0140662 is the ideal molecular function term for HSC82/Hsp90. It captures both the ATP dependence and the protein folding chaperone activity. This should be considered the primary MF annotation for HSC82.
yeast	HSP10	IPR018369,IPR020818	GO:0005524	ATP binding	REMOVE	yes		Remove; ATP binding/hydrolysis belongs to Hsp60 in this system, while Hsp10 regulates the Hsp60 ATPase-driven cycle.
yeast	HSP10	IPR018369,IPR020818,IPR037124	GO:0006457	protein folding	ACCEPT	no		Retain as the principal biological process supported by Hsp10/Hsp60-dependent folding of imported mitochondrial proteins.
yeast	HSP10	IPR020818	GO:0044183	protein folding chaperone	ACCEPT	no		Retain as the co-chaperonin contribution to mitochondrial protein folding. The final annotation should be interpreted with contributes_to semantics because Hsp10 gates and regulates the Hsp60 folding chamber rather than folding substrates independently.
yeast	HSP60	IPR018370	GO:0006457	protein folding	ACCEPT	no		InterPro-based IEA annotation. Redundant with IBA and IMP evidence for the same term, but correct.
yeast	HSP60	IPR001844	GO:0042026	protein refolding	ACCEPT	no		InterPro-based IEA annotation. Consistent with experimental evidence from PMID:1359644 and PMID:9256426 showing HSP60 mediates ATP-dependent refolding of denatured proteins.
yeast	HSP60	IPR001844	GO:0140662	ATP-dependent protein folding chaperone	ACCEPT	no		This is the primary molecular function of HSP60 and the correct replacement for GO:0051082.
yeast	HSP82	IPR001404	GO:0140662	ATP-dependent protein folding chaperone	ACCEPT	no		GO:0140662 is the ideal molecular function term for HSP82/Hsp90. It captures both the ATP dependence and the protein folding chaperone activity. HSP82 binds to client proteins and assists their folding through an ATP-dependent conformational cycle. This should be considered the primary MF annotation for HSP82.
yeast	HST2	IPR017328	GO:0051287	NAD binding	KEEP_AS_NON_CORE	yes		HST2 absolutely requires NAD as a cofactor for its deacetylase activity. Multiple structural studies demonstrate NAD binding in the conserved sirtuin NAD-binding pocket. The Km for NAD is approximately 10.2 uM, indicating physiologically relevant binding affinity. This is a valid cofactor binding annotation but the core molecular function is NAD-dependent lysine deacetylation.
yeast	HST2	IPR003000	GO:0070403	NAD+ binding	KEEP_AS_NON_CORE	yes		Functionally equivalent to GO:0051287 NAD binding but specifies the oxidized NAD+ form that is the actual catalytic substrate. HST2 catalyzes reactions that consume NAD+, and specific binding of the oxidized form is mechanistically relevant. This is mechanistically valid but should remain non-core relative to the deacetylase activity.
yeast	HST3	IPR003000	GO:0070403	NAD+ binding	ACCEPT	no		Essential cofactor binding for catalytic activity. HST3 catalytic mechanism absolutely requires NAD+ binding. The annotation is correctly inferred from the sirtuin domain structure.
yeast	IRE1	IPR010513	GO:0004540	RNA nuclease activity	ACCEPT	no		Correct but less specific than GO:0004521. Acceptable as a broad IEA.
yeast	IRE1	IPR000719,IPR008271	GO:0004672	protein kinase activity	ACCEPT	no		Correct but less specific than GO:0004674. Acceptable as an IEA.
yeast	IRE1	IPR010513	GO:0006397	mRNA processing	ACCEPT	no		Correct. IRE1 endoribonuclease activity directly processes HAC1 pre-mRNA (PMID:9323131).
yeast	LSM1	IPR034104	GO:0000956	nuclear-transcribed mRNA catabolic process	KEEP_AS_NON_CORE	yes		Changed from MODIFY to KEEP_AS_NON_CORE because the review rationale supports retaining the broad parent term as non-core rather than replacing it.
yeast	MDJ1	IPR012724	GO:0005524	ATP binding	MODIFY	yes	GO:0001671 ATPase activator activity	Mdj1 is a J-domain cochaperone that stimulates ATP hydrolysis by mitochondrial Hsp70 Ssc1 rather than an ATP-binding protein itself.
yeast	MDJ1	IPR008971,IPR012724	GO:0006457	protein folding	ACCEPT	no		Retained as supported or plausible for this gene and evidence context.
yeast	MDJ1	IPR012724	GO:0009408	response to heat	ACCEPT	no		Retained as supported or plausible for this gene and evidence context.
yeast	MDJ1	IPR001305	GO:0031072	heat shock protein binding	ACCEPT	no		Retained as supported or plausible for this gene and evidence context.
yeast	MDJ1	IPR001305,IPR008971,IPR012724	GO:0051082	unfolded protein binding	MODIFY	yes	GO:0044183 protein folding chaperone	Modified to align with current curation guidance and improve term specificity.
yeast	NAP1	IPR002164	GO:0006334	nucleosome assembly	ACCEPT	no		Retained as supported or plausible for this gene and evidence context.
yeast	NMD3	IPR039768	GO:0043023	ribosomal large subunit binding	ACCEPT	no		InterPro annotation IPR039768 correctly identifies NMD3 domain and its role in 60S binding. This is supported by experimental data showing direct rRNA binding.
yeast	NTE1	IPR001423	GO:0046470	phosphatidylcholine metabolic process	ACCEPT	no		This annotation accurately reflects NTE1 core enzymatic function as demonstrated experimentally. The protein catalyzes the deacylation of phosphatidylcholine, which is precisely what this GO term describes.
yeast	ORC1	IPR001025	GO:0003682	chromatin binding	ACCEPT	no		Mechanically correct - ORC1 has a BAH domain and binds chromatin/nucleosomes. The more specific nucleosome binding term (GO:0031491) is also annotated with IDA evidence, so this broader term is acceptable as a complementary annotation.
yeast	ORC1	IPR003959	GO:0016887	ATP hydrolysis activity	ACCEPT	no		Core molecular function. ORC1 is an AAA+ ATPase with documented ATP hydrolysis activity. This is essential for ORC complex assembly, DNA binding, and MCM loading. Experimental evidence (IMP PMID:9038340) supports this. Falcon deep research notes Orc1 is the only ORC subunit experimentally demonstrated to possess ATPase activity, reinforcing this as a core enzymatic function.
yeast	PET100	IPR018625	GO:0005739	mitochondrion	ACCEPT	no		Pet100 acts in mitochondrial complex IV assembly, with more precise inner-membrane annotations also present.
yeast	PET100	IPR018625	GO:0033617	mitochondrial respiratory chain complex IV assembly	ACCEPT	no		Experimental yeast studies show Pet100 is required for cytochrome c oxidase assembly and acts on a late complex IV subassembly.
yeast	PFD1	IPR002777	GO:0006457	protein folding	ACCEPT	no		Retain as the direct biological process served by Pfd1-containing prefoldin in cytosolic actin/tubulin folding.
yeast	PFD1	IPR002777	GO:0016272	prefoldin complex	ACCEPT	no		Retain; Pfd1/Gim6 is a component of the heterohexameric prefoldin complex.
yeast	PFD1	IPR002777	GO:0051082	unfolded protein binding	MODIFY	yes	GO:0044183 protein folding chaperone	Unfolded protein binding is mechanistically close but too broad; Pfd1 is best represented as a prefoldin protein-folding cochaperone.
yeast	POB3	IPR000969	GO:0003677	DNA binding	REMOVE	yes		Yeast POB3 does not directly bind DNA. Unlike mammalian SSRP1 which contains an HMG-box domain for DNA binding, POB3 achieves FACT function through cooperation with Nhp6 proteins that provide DNA-binding capability. UniProt itself notes: 'In contrast to the orthologous protein in animals and plants, this protein does not contain a HMG box DNA-binding domain. This function may instead be provided by the HMG box of the associated NHP6A/NHP6B proteins in the FACT complex of yeast.' IEA propagation of mammalian annotations to yeast is inappropriate.
yeast	RAS2	IPR020849	GO:0007165	signal transduction	ACCEPT	no		Appropriate parent term for RAS2 signaling function.
yeast	RAS2	IPR020849	GO:0016020	membrane	ACCEPT	no		Appropriate parent term. RAS2 is a membrane-anchored protein.
yeast	RIM15	IPR001789	GO:0000160	phosphorelay signal transduction system	REMOVE	yes		While RIM15 does contain a response regulatory domain by sequence homology, it does not participate in phosphorelay signal transduction in yeast. RIM15 is activated by inactivation of upstream kinases (TOR, PKA), not by phosphorylation as in typical phosphorelay systems. This is a false positive from InterPro domain annotation.
yeast	RIM15	IPR000719,IPR008271	GO:0004672	protein kinase activity	ACCEPT	no		RIM15 is correctly inferred as a protein kinase via InterPro domain annotation. While GO:0004674 is more specific, this parent term is still valid and commonly annotated.
yeast	ROT1	IPR019623	GO:0005783	endoplasmic reticulum	ACCEPT	no		Rot1 functions in the ER; the ER membrane term gives the more precise core location.
yeast	ROT1	IPR019623	GO:0006458	'de novo' protein folding	ACCEPT	no		Rot1 is an ER chaperone that supports folding/maturation of newly synthesized secretory-pathway proteins.
yeast	RTT109	IPR016849	GO:0006325	chromatin organization	ACCEPT	no		H3K56 acetylation creates relaxed chromatin structure on nascent DNA during replication and facilitates proper nucleosome positioning and assembly. Multiple biochemical studies confirm chromatin structural changes.
yeast	RTT109	IPR013178	GO:0006355	regulation of DNA-templated transcription	ACCEPT	no		RTT109 suppresses transcription at early-replicating genes through H3K56 acetylation, preventing transcriptional upregulation proportional to DNA content increase.
yeast	RTT109	IPR016849	GO:0010484	histone H3 acetyltransferase activity	ACCEPT	no		RTT109 catalyzes acetylation of histone H3 at multiple lysine residues (K56, K9, K27, K14, K23) depending on histone chaperone cofactor.
yeast	SAS2	IPR002717	GO:0006355	regulation of DNA-templated transcription	ACCEPT	no		SAS2 regulates transcription through histone acetylation-mediated chromatin organization. The GO:0006355 term is appropriately intermediate between general transcription (GO:0006351) and specific processes (silencing). IBA/IEA inference from HAT domain function is justified.
yeast	SAS3	IPR002717	GO:0006355	regulation of DNA-templated transcription	ACCEPT	no		Accepted as concordant with SAS3 molecular role and literature-supported complex/process context. Falcon deep research supports a chromatin-context-sensitive transcriptional-regulatory role, with NuA3 reader modules targeting acetylation to active chromatin marks.
yeast	SER3	IPR006139	GO:0016616	oxidoreductase activity, acting on the CH-OH group of donors, NAD or NADP as acceptor	ACCEPT	no		This accurately describes the biochemical mechanism of Ser3p, which oxidizes the CH-OH group of 3-phosphoglycerate using NAD+ as electron acceptor. This is mechanistically correct and more specific than the general oxidoreductase activity term.
yeast	SER3	IPR006139,IPR006140	GO:0051287	NAD binding	ACCEPT	no		Correct - Ser3p requires NAD+ as a cofactor for its dehydrogenase activity. The protein contains a Rossmann fold domain for NAD+ binding, which is conserved across phosphoglycerate dehydrogenases.
yeast	SET1	IPR017111,IPR044570	GO:0042800	histone H3K4 methyltransferase activity	ACCEPT	no		Core molecular function annotation. IEA from InterPro recognition of SET domain is appropriate. Extensive literature confirms this is SET1 primary function. Duplicate of annotation 1 with different evidence source.
yeast	SET1	IPR017111	GO:0048188	Set1C/COMPASS complex	ACCEPT	no		Core structural annotation. Duplicate of annotation 2 with different evidence. InterPro detection of SET domain-containing protein appropriately infers COMPASS complex membership.
yeast	SHQ1	IPR039742	GO:0000493	box H/ACA snoRNP assembly	ACCEPT	no		Shq1 is a conserved H/ACA assembly factor and yeast experiments directly support this process.
yeast	SHY1	IPR002994	GO:0016020	membrane	MODIFY	yes	GO:0005743 mitochondrial inner membrane	Replace generic membrane with the experimentally supported mitochondrial inner membrane location.
yeast	SIR2	IPR003000	GO:0070403	NAD+ binding	ACCEPT	no		NAD+ is the obligate substrate/cofactor for SIR2 catalytic activity. Crystal structures show extensive NAD+ binding interactions. The NAD-dependence is a defining feature distinguishing sirtuins from other deacetylases.
yeast	SIR3	IPR001025	GO:0003682	chromatin binding	ACCEPT	no		SIR3 directly binds to chromatin and nucleosomes, which is central to its function in heterochromatin formation. This is a core molecular mechanism.
yeast	SNF5	IPR006939	GO:0000228	nuclear chromosome	ACCEPT	no		SNF5 is demonstrated to localize to nuclear chromosomes as a core SWI/SNF complex subunit (PMID:2233708, PMID:22932476). The term correctly identifies a major site of SNF5 function. IEA evidence from InterPro annotation is conservative and appropriate for this well-established localization. This represents core subcellular localization of the protein.
yeast	SNF5	IPR006939	GO:0006338	chromatin remodeling	ACCEPT	no		Chromatin remodeling is a primary CORE function of SNF5. SNF5 is essential for SWI/SNF catalytic activity, directly engaging nucleosomes through arginine-rich repeat domains that bind the histone acidic patch (deep research). SNF5 deletion reduces nucleosome remodeling efficiency 2-3 fold and uncouples ATP hydrolysis from productive DNA translocation. This is not a secondary or peripheral function but rather represents SNF5's primary biochemical role. Multiple experimental studies demonstrate this (PMID:11163188, PMID:1459453, cryo-EM structures in deep research).
yeast	SOD2	IPR001189,IPR019831,IPR019832,IPR019833	GO:0006801	superoxide metabolic process	ACCEPT	no		"This annotation appropriately captures SOD2's involvement in superoxide metabolism through the dismutation reaction. However, it is broader than the more specific functional process ""removal of superoxide radicals"" (GO:0019430) which more precisely describes the biological outcome. The annotation is not incorrect but represents a higher-level categorization of the more specific process."
yeast	SSA1	IPR013126	GO:0016887	ATP hydrolysis activity	ACCEPT	no		Correct. Redundant with IBA and IDA annotations but acceptable.
yeast	SSA2	IPR013126	GO:0016887	ATP hydrolysis activity	ACCEPT	no		Correct. Redundant with IBA and ISS annotations but acceptable.
yeast	SSA4	IPR013126	GO:0016887	ATP hydrolysis activity	ACCEPT	no		Accurate catalytic activity intrinsic to the Hsp70 chaperone cycle.
yeast	SSB1	IPR035979	GO:0003676	nucleic acid binding	KEEP_AS_NON_CORE	yes		Correct but uninformatively general; superseded by more specific RNA/mRNA binding annotations.
yeast	SSQ1	IPR013126	GO:0016887	ATP hydrolysis activity	ACCEPT	no		Retained as supported or plausible for this gene and evidence context.
yeast	SSZ1	IPR013126	GO:0016887	ATP hydrolysis activity	REMOVE	yes		InterPro family-level inference of ATPase activity is incorrect for Ssz1, a non-canonical Hsp70 that does not hydrolyze ATP (and for which hydrolysis is dispensable).
yeast	SUI2	IPR003029	GO:0003676	nucleic acid binding	REMOVE	yes		"eIF2α does not function as a nucleic acid-binding protein in the traditional sense. The RNA-binding domains identified by InterPro are structural components that facilitate methionyl-tRNA recognition, not general nucleic acid binding. eIF2α specifically recognizes and binds the methionyl-tRNA through protein-RNA interactions, but this is better captured by the term ""methionyl-initiator methionine tRNA binding"" (GO:1990856), not the generic nucleic acid binding. Including this term conflates structural domains with functional role and is misleading about eIF2α's mechanism of action."
yeast	SWI2	IPR017956	GO:0003677	DNA binding	ACCEPT	no		While correct and subsumed by more specific nucleosomal DNA binding annotations, it is consistent with IBA evidence and appropriate to keep.
yeast	SWI2	IPR029295	GO:0042393	histone binding	KEEP_AS_NON_CORE	yes		While correct, this is a general annotation subsumed by more specific histone reader activity annotations (H3, H4 acetyl-lysine binding). Keep for completeness but note more specific annotations exist.
yeast	SWI2	IPR014978	GO:0006355	regulation of DNA-templated transcription	KEEP_AS_NON_CORE	yes		General transcriptional regulation term but more specific annotations (positive regulation of RNAP II transcription) are more informative.
yeast	TCP1	IPR002194,IPR012715	GO:0016887	ATP hydrolysis activity	ACCEPT	no		Correct. Each CCT subunit contributes ATPase activity to the chaperonin cycle. InterPro-based annotation is well supported.
yeast	TCP1	IPR017998	GO:0140662	ATP-dependent protein folding chaperone	ACCEPT	no		Correct and the most appropriate MF term. GO:0140662 is the proper replacement for the obsoleting GO:0051082. As a complex subunit, the qualifier should ideally be contributes_to rather than enables, but the IEA annotation is correct in substance.
yeast	TIM22	IPR039175	GO:0042721	TIM22 mitochondrial import inner membrane insertion complex	ACCEPT	no		Correct. InterPro domain IPR039175 is specific to TIM22 family members. Redundant with experimental annotations but not incorrect.
yeast	TIM22	IPR039175	GO:0045039	protein insertion into mitochondrial inner membrane	ACCEPT	no		Correct. Redundant with experimental annotations but the InterPro mapping is sound.
yeast	TOR1	IPR009076,IPR036738	GO:0044877	protein-containing complex binding	ACCEPT	no		InterPro FRB domain (IPR009076, IPR036738) mediates FKBP-rapamycin complex binding. TORC1 forms complex with rapamycin-FKBP. IEA from InterPro is reliable.
yeast	TSA1	IPR019479	GO:0051920	peroxiredoxin activity	ACCEPT	no		Accurate MF supported by domain/family (AhpC/Prx1) inference and direct biochemistry.
yeast	TSR4	IPR007320	GO:0005737	cytoplasm	ACCEPT	no		Tsr4 acts in the cytoplasm on nascent Rps2/uS5 before nuclear import.
yeast	UBP3	IPR001394	GO:0016579	protein deubiquitination	ACCEPT	no		IEA appropriately infers the biological process from conserved deubiquitinase domain. All ubiquitin-specific proteases (USPs) catalyze protein deubiquitination as fundamental function.
yeast	VMA22	IPR040357	GO:0070072	vacuolar proton-transporting V-type ATPase complex assembly	ACCEPT	no		Although this particular annotation is electronic, it matches the experimentally demonstrated core role of Vma22 in V-ATPase assembly.
yeast	YDJ1	IPR012724	GO:0005524	ATP binding	MARK_AS_OVER_ANNOTATED	yes		YDJ1 regulates Hsp70 ATPase activity but does not itself bind ATP. The InterPro mapping appears to be overly broad. The J-domain stimulates ATP hydrolysis by Hsp70 but the DnaJ protein itself is not an ATPase or ATP-binding protein.
yeast	YDJ1	IPR008971,IPR012724,IPR044713	GO:0006457	protein folding	ACCEPT	no		Protein folding is a core biological process for YDJ1, supported by multiple experimental studies including its role in de novo protein folding (PMID:10567418) and protein refolding (PMID:9674429).
yeast	YDJ1	IPR012724	GO:0009408	response to heat	ACCEPT	no		Correct but less specific than GO:0034605. The IEA is consistent with the established role of YDJ1 as a heat shock protein.
yeast	YDJ1	IPR044713	GO:0030544	Hsp70 protein binding	ACCEPT	no		Hsp70 binding is a core interaction for YDJ1 as a J-domain co-chaperone. However, this is a binding term and the functional relationship is better captured by GO:0001671 (ATPase activator activity). Acceptable as an IEA.
yeast	YDJ1	IPR001305	GO:0031072	heat shock protein binding	ACCEPT	no		Correct but less specific than GO:0030544 (Hsp70 protein binding). Acceptable as a broad IEA annotation.
yeast	YDJ1	IPR001305,IPR008971,IPR012724	GO:0051082	unfolded protein binding	MODIFY	yes	GO:0044183 protein folding chaperone	GO:0051082 is proposed for obsoletion. YDJ1 is an active co-chaperone, not merely a passive binder of unfolded proteins. Should be replaced with GO:0044183.