gene term label rules action generality descendants category family cue manual_mode reason 9AVES/TAS1R1 GO:0050909 sensory perception of taste ARBA:ARBA00028227 KEEP_AS_NON_CORE general (21-200) 22 9AVES/TAS1R3 GO:0050909 sensory perception of taste ARBA:ARBA00028227 KEEP_AS_NON_CORE general (21-200) 22 9CAUD/g022 GO:0006259 DNA metabolic process REMOVE very general (>200 descendants) 285 TOO_GENERAL true but uninformative manual TOO_GENERAL Appropriately identified as too general. DNA metabolic process encompasses many different processes including repair, recombination, and degradation. The viral-specific replication terms are more informative and accurate for this context. Retired because absent from GOA as of the 2026-07-27 QuickGO release (GOA refresh 2026-09-29); the review is kept for provenance. 9CAUD/g022 GO:0071897 DNA biosynthetic process ARBA:ARBA00028515 KEEP_AS_NON_CORE general (21-200) 31 9CAUD/g022 GO:0140640 catalytic activity, acting on a nucleic acid ARBA:ARBA00026869 REMOVE very general (>200 descendants) 444 TOO_GENERAL true but uninformative manual TOO_GENERAL Adds no information beyond GO:0003887; treated the same way as the other generic MF rows here (transferase activity, nucleotidyltransferase activity). 9POAL/CDT1 GO:0010038 response to metal ion ARBA:ARBA00028342 KEEP_AS_NON_CORE general (21-200) 64 9POAL/NCGR_LOCUS10166 GO:0005783 endoplasmic reticulum UNDECIDED general (21-200) 100 9POAL/NCGR_LOCUS1270 GO:0005985 sucrose metabolic process ARBA:ARBA00045052 UNDECIDED specific (1-20) 4 9POAL/NCGR_LOCUS29329 GO:0006531 aspartate metabolic process ARBA:ARBA00085438 ACCEPT specific (1-20) 3 9POAL/NCGR_LOCUS67308 GO:0045273 respiratory chain complex II (succinate dehydrogenase) ARBA:ARBA00027643 ACCEPT leaf (0) 0 9POAL/psbA GO:0009536 plastid ARBA:ARBA00027316 KEEP_AS_NON_CORE general (21-200) 124 9POAL/rbcL GO:0009536 plastid ARBA:ARBA00027316 KEEP_AS_NON_CORE general (21-200) 124 ACET2/P10477 GO:2000884 glucomannan catabolic process ARBA:ARBA00085700 ACCEPT leaf (0) 0 AILME/A0A7N5KEZ3_AILME GO:0005829 cytosol ARBA:ARBA00029243 MARK_AS_OVER_ANNOTATED general (21-200) 73 TOO_GENERAL true but uninformative broad Biologically the relevant location of a KAP is the cross-linked keratin matrix of the cornified hair/claw, captured by the keratin-filament term, not free cytosol. The cytosol annotation is a broad ARBA rule-based assignment (GO_REF:0000117) seen across the KRTAP family rather than a gene-specific finding, so it is a generic over-annotation rather than an informative, gene-specific localization. ANOGA/NPAC GO:0003682 chromatin binding ARBA:ARBA00027831 ACCEPT specific (1-20) 10 ARAHY/A0A444Z7V7 GO:0005737 cytoplasm ARBA:ARBA00026971 MARK_AS_OVER_ANNOTATED very general (>200 descendants) 1146 TOO_GENERAL true but uninformative uninformative ARBA-derived annotation. While the catalytic domain is cytoplasm-facing, the protein is an integral membrane glycosyltransferase with 7 predicted transmembrane helices. Calling it cytoplasmic is uninformative given that more specific membrane localizations are already annotated. ARAHY/A0A444Z7V7 GO:0009409 response to cold ARBA:ARBA00028088 MARK_AS_OVER_ANNOTATED specific (1-20) 5 INDIRECT_EFFECT overreach secondary ARBA-derived annotation. Cold-responsive transcriptional changes in cell wall genes are a secondary consequence of stress-induced growth adjustments, not a direct molecular function of this glycosyltransferase. No specific evidence links CSLD3-type proteins to cold stress response pathways. ARAHY/A0A444Z7V7 GO:0012505 endomembrane system ARBA:ARBA00028953 KEEP_AS_NON_CORE very general (>200 descendants) 357 ARAHY/A0A444Z7V7 GO:0051753 mannan synthase activity ARBA:ARBA00090002 ACCEPT leaf (0) 0 ARATH/ABCB19 GO:0008361 regulation of cell size ARBA:ARBA00091970 KEEP_AS_NON_CORE general (21-200) 35 ARATH/ABCB19 GO:0009555 pollen development ARBA:ARBA00092333 KEEP_AS_NON_CORE specific (1-20) 11 ARATH/ABCB19 GO:0009637 response to blue light ARBA:ARBA00026676 KEEP_AS_NON_CORE specific (1-20) 7 ARATH/ABCB19 GO:0009640 photomorphogenesis ARBA:ARBA00091863 KEEP_AS_NON_CORE specific (1-20) 1 ARATH/ABCB19 GO:0009733 response to auxin ARBA:ARBA00028751 KEEP_AS_NON_CORE specific (1-20) 7 ARATH/ABCB19 GO:0009741 response to brassinosteroid ARBA:ARBA00085261 KEEP_AS_NON_CORE specific (1-20) 3 ARATH/ABCB19 GO:0009926 auxin polar transport ARBA:ARBA00084439 ACCEPT specific (1-20) 3 ARATH/ABCB19 GO:0010329 auxin efflux transmembrane transporter activity ARBA:ARBA00092978 ACCEPT leaf (0) 0 ARATH/ABCB19 GO:0043481 anthocyanin accumulation in tissues in response to UV light ARBA:ARBA00085884 KEEP_AS_NON_CORE leaf (0) 0 ARATH/ABCB19 GO:0048443 stamen development ARBA:ARBA00089674 KEEP_AS_NON_CORE specific (1-20) 16 ARATH/ABCB19 GO:0048461 flower structural organization ARBA:ARBA00095377 KEEP_AS_NON_CORE specific (1-20) 6 ARATH/ABCB19 GO:0051510 regulation of unidimensional cell growth ARBA:ARBA00088642 KEEP_AS_NON_CORE specific (1-20) 12 ARATH/ABCB19 GO:0090627 plant epidermal cell differentiation ARBA:ARBA00087997 KEEP_AS_NON_CORE specific (1-20) 20 ARATH/ABCB19 GO:1900459 positive regulation of brassinosteroid mediated signaling pathway ARBA:ARBA00093743 KEEP_AS_NON_CORE leaf (0) 0 ARATH/ABI1 GO:0004722 protein serine/threonine phosphatase activity ARBA:ARBA00027653 ACCEPT specific (1-20) 11 ARATH/ABI5 GO:0007165 signal transduction ARBA:ARBA00029050 MARK_AS_OVER_ANNOTATED very general (>200 descendants) 937 INDIRECT_EFFECT overreach downstream ABI5 is a downstream transcriptional effector of ABA signaling rather than a general signal transducer. The generic parent over-annotates; the more specific abscisic acid-activated signaling pathway (a UniProt keyword annotation) captures this better. ARATH/ABI5 GO:0009414 response to water deprivation ARBA:ARBA00028094 KEEP_AS_NON_CORE specific (1-20) 7 ARATH/ABI5 GO:0009651 response to salt stress ARBA:ARBA00026582 KEEP_AS_NON_CORE specific (1-20) 8 ARATH/ABI5 GO:0009737 response to abscisic acid ARBA:ARBA00033526 ACCEPT specific (1-20) 5 ARATH/ABI5 GO:0009845 seed germination ARBA:ARBA00084883 ACCEPT specific (1-20) 2 ARATH/ABI5 GO:0043565 sequence-specific DNA binding ARBA:ARBA00026779 ACCEPT general (21-200) 60 ARATH/ABI5 GO:1901701 cellular response to oxygen-containing compound ARBA:ARBA00027483 MARK_AS_OVER_ANNOTATED very general (>200 descendants) 308 TOO_GENERAL true but uninformative Uninformative Uninformative high-level grouping term derived automatically; the specific response to abscisic acid term (GO:0009737) is the appropriate annotation. ARATH/AFB2 GO:0009733 response to auxin ARBA:ARBA00028751 ACCEPT specific (1-20) 7 ARATH/AG GO:0048440 carpel development ARBA:ARBA00089672 ACCEPT specific (1-20) 12 ARATH/AGO1 GO:0010016 shoot system morphogenesis ARBA:ARBA00091374 KEEP_AS_NON_CORE general (21-200) 39 ARATH/AGO1 GO:0051607 defense response to virus ARBA:ARBA00026923 MODIFY specific (1-20) 5 NEEDS_MORE_SPECIFIC true but uninformative replacement term The electronic defense annotation is supported by ago1 virus hypersensitivity and AGO1 loading of viral siRNAs in PMID:11910010 and PMID:17158744. The RNAi-specific antiviral term captures the demonstrated mechanism more precisely. ARATH/AHK2 GO:0009414 response to water deprivation ARBA:ARBA00028094 KEEP_AS_NON_CORE specific (1-20) 7 ARATH/AHK2 GO:0009651 response to salt stress ARBA:ARBA00026582 KEEP_AS_NON_CORE specific (1-20) 8 ARATH/AHK2 GO:0009884 cytokinin receptor activity ARBA:ARBA00084931 ACCEPT specific (1-20) 2 ARATH/AHK2 GO:0009909 regulation of flower development ARBA:ARBA00043323 KEEP_AS_NON_CORE specific (1-20) 2 ARATH/AHK2 GO:0010029 regulation of seed germination ARBA:ARBA00091417 KEEP_AS_NON_CORE specific (1-20) 2 ARATH/AHK2 GO:0010087 phloem or xylem histogenesis ARBA:ARBA00091454 KEEP_AS_NON_CORE specific (1-20) 7 ARATH/AHK2 GO:0010271 regulation of chlorophyll catabolic process ARBA:ARBA00090628 KEEP_AS_NON_CORE specific (1-20) 2 ARATH/AHK2 GO:0034757 negative regulation of iron ion transport ARBA:ARBA00085303 KEEP_AS_NON_CORE specific (1-20) 3 ARATH/AHK2 GO:0043424 protein histidine kinase binding ARBA:ARBA00085794 KEEP_AS_NON_CORE leaf (0) 0 ARATH/AHK2 GO:0048509 regulation of meristem development ARBA:ARBA00091779 KEEP_AS_NON_CORE specific (1-20) 5 ARATH/AHK2 GO:0070417 cellular response to cold ARBA:ARBA00029183 KEEP_AS_NON_CORE specific (1-20) 1 ARATH/AHK2 GO:0071215 cellular response to abscisic acid stimulus ARBA:ARBA00090666 KEEP_AS_NON_CORE specific (1-20) 2 ARATH/AHK2 GO:0080117 secondary growth ARBA:ARBA00084428 KEEP_AS_NON_CORE leaf (0) 0 ARATH/AHK3 GO:0009414 response to water deprivation ARBA:ARBA00028094 KEEP_AS_NON_CORE specific (1-20) 7 ARATH/AHK3 GO:0009651 response to salt stress ARBA:ARBA00026582 KEEP_AS_NON_CORE specific (1-20) 8 ARATH/AHK3 GO:0009884 cytokinin receptor activity ARBA:ARBA00084931 ACCEPT specific (1-20) 2 ARATH/AHK3 GO:0009909 regulation of flower development ARBA:ARBA00043323 KEEP_AS_NON_CORE specific (1-20) 2 ARATH/AHK3 GO:0010029 regulation of seed germination ARBA:ARBA00091417 KEEP_AS_NON_CORE specific (1-20) 2 ARATH/AHK3 GO:0010087 phloem or xylem histogenesis ARBA:ARBA00091454 KEEP_AS_NON_CORE specific (1-20) 7 ARATH/AHK3 GO:0010271 regulation of chlorophyll catabolic process ARBA:ARBA00090628 KEEP_AS_NON_CORE specific (1-20) 2 ARATH/AHK3 GO:0034757 negative regulation of iron ion transport ARBA:ARBA00085303 KEEP_AS_NON_CORE specific (1-20) 3 ARATH/AHK3 GO:0043424 protein histidine kinase binding ARBA:ARBA00085794 KEEP_AS_NON_CORE leaf (0) 0 ARATH/AHK3 GO:0048509 regulation of meristem development ARBA:ARBA00091779 KEEP_AS_NON_CORE specific (1-20) 5 ARATH/AHK3 GO:0070417 cellular response to cold ARBA:ARBA00029183 KEEP_AS_NON_CORE specific (1-20) 1 ARATH/AHK3 GO:0071215 cellular response to abscisic acid stimulus ARBA:ARBA00090666 KEEP_AS_NON_CORE specific (1-20) 2 ARATH/AHK3 GO:0080117 secondary growth ARBA:ARBA00084428 KEEP_AS_NON_CORE leaf (0) 0 ARATH/AHK4 GO:0006970 response to osmotic stress ARBA:ARBA00026252 KEEP_AS_NON_CORE general (21-200) 29 ARATH/AHK4 GO:0009414 response to water deprivation ARBA:ARBA00028094 KEEP_AS_NON_CORE specific (1-20) 7 ARATH/AHK4 GO:0009884 cytokinin receptor activity ARBA:ARBA00084931 ACCEPT specific (1-20) 2 ARATH/AHK4 GO:0010029 regulation of seed germination ARBA:ARBA00091417 KEEP_AS_NON_CORE specific (1-20) 2 ARATH/AHK4 GO:0033554 cellular response to stress ARBA:ARBA00028184 MARK_AS_OVER_ANNOTATED very general (>200 descendants) 285 TOO_GENERAL true but uninformative general Too general to be informative; specific cytokinin-dependent developmental and stress outputs are captured by other annotations. ARATH/AHK4 GO:0043424 protein histidine kinase binding ARBA:ARBA00085794 KEEP_AS_NON_CORE leaf (0) 0 ARATH/AHK4 GO:0048509 regulation of meristem development ARBA:ARBA00091779 KEEP_AS_NON_CORE specific (1-20) 5 ARATH/AHK4 GO:0048831 regulation of shoot system development ARBA:ARBA00043299 KEEP_AS_NON_CORE specific (1-20) 3 ARATH/AHK4 GO:0160109 plant gross anatomical part developmental process ARBA:ARBA00098140 MARK_AS_OVER_ANNOTATED very general (>200 descendants) 262 TOO_GENERAL true but uninformative general Too general to be informative; specific cytokinin-dependent developmental and stress outputs are captured by other annotations. ARATH/AHK4 GO:1901701 cellular response to oxygen-containing compound ARBA:ARBA00027483 MARK_AS_OVER_ANNOTATED very general (>200 descendants) 308 TOO_GENERAL true but uninformative general Too general to be informative; specific cytokinin-dependent developmental and stress outputs are captured by other annotations. ARATH/AHP1 GO:0009736 cytokinin-activated signaling pathway ARBA:ARBA00028777 ACCEPT specific (1-20) 3 ARATH/AHP1 GO:0160109 plant gross anatomical part developmental process ARBA:ARBA00098140 MARK_AS_OVER_ANNOTATED very general (>200 descendants) 262 INDIRECT_EFFECT overreach indirect Too general to be informative; AHP1 affects development indirectly via cytokinin and CKI1 phosphorelay signaling. ARATH/AOP2 GO:0016706 2-oxoglutarate-dependent dioxygenase activity ARBA:ARBA00027633 ACCEPT general (21-200) 65 ARATH/AOP2 GO:0019761 glucosinolate biosynthetic process ARBA:ARBA00085760 ACCEPT specific (1-20) 2 ARATH/AP2 GO:0003677 DNA binding ARBA:ARBA00029224 MODIFY general (21-200) 130 NEEDS_MORE_SPECIFIC true but uninformative replacement term Replace generic DNA binding with AP2's more informative transcription factor and promoter/cis-regulatory binding activities. ARATH/AP3 GO:0048437 floral organ development ARBA:ARBA00026899 KEEP_AS_NON_CORE general (21-200) 48 ARATH/ARR12 GO:0009414 response to water deprivation ARBA:ARBA00028094 KEEP_AS_NON_CORE specific (1-20) 7 ARATH/ARR12 GO:0009611 response to wounding ARBA:ARBA00026469 MARK_AS_OVER_ANNOTATED general (21-200) 40 UNCLASSIFIED unclassified Type-B ARR signaling contributes to wound-induced callus formation via cytokinin, but ARR12 is not established as part of the wound response itself. ARATH/ARR12 GO:0010082 regulation of root meristem growth ARBA:ARBA00091464 KEEP_AS_NON_CORE leaf (0) 0 ARATH/ARR12 GO:0010380 regulation of chlorophyll biosynthetic process ARBA:ARBA00093133 KEEP_AS_NON_CORE specific (1-20) 2 ARATH/ARR12 GO:0010492 maintenance of shoot apical meristem identity ARBA:ARBA00092785 KEEP_AS_NON_CORE leaf (0) 0 ARATH/ARR12 GO:0031537 regulation of anthocyanin metabolic process ARBA:ARBA00085490 KEEP_AS_NON_CORE specific (1-20) 8 ARATH/ARR12 GO:0048367 shoot system development ARBA:ARBA00026422 KEEP_AS_NON_CORE general (21-200) 111 ARATH/ARR12 GO:0080022 primary root development ARBA:ARBA00084779 KEEP_AS_NON_CORE leaf (0) 0 ARATH/ARR12 GO:0080036 regulation of cytokinin-activated signaling pathway ARBA:ARBA00084807 MODIFY specific (1-20) 2 TOO_SPECIFIC overreach replacement term ARR12 is an integral component of the cytokinin-activated signaling pathway (its terminal transcription factor), not a separate regulator of it; the pathway term is more accurate. ARATH/ARR12 GO:0080113 regulation of seed growth ARBA:ARBA00084427 KEEP_AS_NON_CORE leaf (0) 0 ARATH/ARR5 GO:0006355 regulation of DNA-templated transcription ARBA:ARBA00028138 MARK_AS_OVER_ANNOTATED general (21-200) 140 INDIRECT_EFFECT overreach indirect ARR5 lacks a DNA-binding domain; it dampens cytokinin-induced transcription indirectly by negative feedback on the phosphorelay (e.g. at the level of AHPs), which is better captured by negative regulation of cytokinin-activated signaling pathway. ARATH/AT1G06680 GO:0009534 chloroplast thylakoid ARBA:ARBA00027312 ACCEPT specific (1-20) 15 ARATH/AT1G74310 GO:0009408 response to heat ARBA:ARBA00028092 ACCEPT specific (1-20) 7 ARATH/AT5G02500 GO:0009408 response to heat ARBA:ARBA00028092 ACCEPT specific (1-20) 7 ARATH/AT5G02500 GO:0009615 response to virus ARBA:ARBA00026492 KEEP_AS_NON_CORE specific (1-20) 9 ARATH/BAM1 GO:0009934 regulation of meristem structural organization ARBA:ARBA00084446 ACCEPT leaf (0) 0 ARATH/BAM1 GO:0010075 regulation of meristem growth ARBA:ARBA00091443 ACCEPT specific (1-20) 5 ARATH/BAM1 GO:0033612 receptor serine/threonine kinase binding ARBA:ARBA00084550 ACCEPT specific (1-20) 5 ARATH/BAM1 GO:0048229 gametophyte development ARBA:ARBA00089744 KEEP_AS_NON_CORE general (21-200) 26 ARATH/BAM1 GO:0048437 floral organ development ARBA:ARBA00026899 KEEP_AS_NON_CORE general (21-200) 48 ARATH/BES1 GO:0006355 regulation of DNA-templated transcription ARBA:ARBA00028138 ACCEPT general (21-200) 140 ARATH/BRC1 GO:0160109 plant gross anatomical part developmental process ARBA:ARBA00098140 MARK_AS_OVER_ANNOTATED very general (>200 descendants) 262 TOO_GENERAL true but uninformative general Very general; BRC1's role is specifically in axillary bud dormancy and branching. ARATH/BRI1 GO:0009416 response to light stimulus ARBA:ARBA00028128 KEEP_AS_NON_CORE general (21-200) 101 ARATH/BRI1 GO:0009791 post-embryonic development ARBA:ARBA00029007 KEEP_AS_NON_CORE very general (>200 descendants) 271 ARATH/BZR1 GO:0006355 regulation of DNA-templated transcription ARBA:ARBA00028138 ACCEPT general (21-200) 140 ARATH/CCA1 GO:0010468 regulation of gene expression ARBA:ARBA00028334 ACCEPT very general (>200 descendants) 874 ARATH/CERK1 GO:0009617 response to bacterium ARBA:ARBA00026494 KEEP_AS_NON_CORE general (21-200) 53 ARATH/CERK1 GO:1901701 cellular response to oxygen-containing compound ARBA:ARBA00027483 MARK_AS_OVER_ANNOTATED very general (>200 descendants) 308 TOO_GENERAL true but uninformative Uninformative Uninformatively broad ARBA-derived annotation; the specific and accurate response terms (cellular response to chitin, GO:0071323) are already present. Not wrong but over-general. ARATH/CLF GO:0050793 regulation of developmental process ARBA:ARBA00028689 ACCEPT very general (>200 descendants) 1542 ARATH/CLF GO:0141044 epigenetic programming in the endosperm ARBA:ARBA00095392 KEEP_AS_NON_CORE leaf (0) 0 ARATH/CLV1 GO:0032502 developmental process ARBA:ARBA00028739 MODIFY very general (>200 descendants) 4075 NEEDS_MORE_SPECIFIC true but uninformative replacement term Replace the broad ARBA developmental annotation with the existing meristem-specific process. ARATH/CLV1 GO:0050793 regulation of developmental process ARBA:ARBA00028689 MODIFY very general (>200 descendants) 1542 NEEDS_MORE_SPECIFIC true but uninformative replacement term Use the more precise meristem process for the core developmental role of CLV1. ARATH/CLV2 GO:0007165 signal transduction ARBA:ARBA00029050 MODIFY very general (>200 descendants) 937 NEEDS_MORE_SPECIFIC true but uninformative replacement term Use the more informative parent for cell-surface receptor signalling. No CLE-specific GO process term exists. ARATH/COP1 GO:0042802 identical protein binding ARBA:ARBA00027930 ACCEPT specific (1-20) 1 ARATH/CPC GO:0009653 anatomical structure morphogenesis ARBA:ARBA00026583 MARK_AS_OVER_ANNOTATED very general (>200 descendants) 1501 TOO_GENERAL true but uninformative broad CPC acts in epidermal cell fate specification, not in morphogenesis of an anatomical structure; the term is too broad to be informative and misplaces the role. ARATH/CPC GO:0048731 system development ARBA:ARBA00027702 MARK_AS_OVER_ANNOTATED very general (>200 descendants) 2438 TOO_GENERAL true but uninformative Uninformative Uninformative high-level term; more specific epidermal terms capture CPC's role. ARATH/CPC GO:0090558 plant epidermis development ARBA:ARBA00047265 KEEP_AS_NON_CORE general (21-200) 34 ARATH/CPC GO:0090627 plant epidermal cell differentiation ARBA:ARBA00087997 ACCEPT specific (1-20) 20 ARATH/CRY1 GO:0005524 ATP binding ARBA:ARBA00027027 KEEP_AS_NON_CORE leaf (0) 0 ARATH/CRY1 GO:0042803 protein homodimerization activity ARBA:ARBA00027933 ACCEPT leaf (0) 0 ARATH/CRY1 GO:0071949 FAD binding ARBA:ARBA00084586 ACCEPT leaf (0) 0 ARATH/CRY1 GO:0009414 response to water deprivation ARBA:ARBA00028094 MARK_AS_OVER_ANNOTATED specific (1-20) 7 INDIRECT_EFFECT overreach indirect The direct evidence is that CRY1/CRY2 regulate blue-light stomatal opening and water loss. Calling CRY1 a water-deprivation response gene overstates an indirect physiological consequence. ARATH/CRY1 GO:0009638 phototropism ARBA:ARBA00091921 KEEP_AS_NON_CORE leaf (0) 0 ARATH/CRY1 GO:0009646 response to absence of light ARBA:ARBA00091861 KEEP_AS_NON_CORE specific (1-20) 3 ARATH/CRY1 GO:0009785 blue light signaling pathway ARBA:ARBA00028968 ACCEPT specific (1-20) 1 ARATH/CRY1 GO:0009791 post-embryonic development ARBA:ARBA00029007 MODIFY very general (>200 descendants) 271 NEEDS_MORE_SPECIFIC true but uninformative replacement term The evidence supports CRY1 regulation of photomorphogenesis and light-dependent growth, not a generic role in overall development. ARATH/CRY1 GO:0010075 regulation of meristem growth ARBA:ARBA00091443 KEEP_AS_NON_CORE specific (1-20) 5 ARATH/CRY1 GO:0010118 stomatal movement ARBA:ARBA00090909 KEEP_AS_NON_CORE specific (1-20) 3 ARATH/CRY1 GO:0010244 response to low fluence blue light stimulus by blue low-fluence system ARBA:ARBA00090587 KEEP_AS_NON_CORE leaf (0) 0 ARATH/CRY1 GO:0010617 circadian regulation of calcium ion oscillation ARBA:ARBA00091901 KEEP_AS_NON_CORE leaf (0) 0 ARATH/CRY1 GO:0042752 regulation of circadian rhythm ARBA:ARBA00088520 KEEP_AS_NON_CORE general (21-200) 21 ARATH/CRY1 GO:0048580 regulation of post-embryonic development ARBA:ARBA00043383 MODIFY general (21-200) 51 OTHER_TERM different term needed replacement term The evidence supports CRY1 regulation of photomorphogenesis and light-dependent growth, not a generic role in overall development. ARATH/CRY1 GO:0048731 system development ARBA:ARBA00027702 MODIFY very general (>200 descendants) 2438 OTHER_TERM different term needed replacement term The evidence supports CRY1 regulation of photomorphogenesis and light-dependent growth, not a generic role in overall development. ARATH/CRY1 GO:0072387 flavin adenine dinucleotide metabolic process ARBA:ARBA00090789 MODIFY specific (1-20) 4 OTHER_TERM different term needed replacement term CRY1 binds FAD and undergoes flavin photoreduction during blue-light signaling, but there is no evidence that CRY1 is part of FAD biosynthesis, degradation, or cofactor metabolism as a biological process. ARATH/CRY1 GO:1901371 regulation of leaf morphogenesis ARBA:ARBA00092524 KEEP_AS_NON_CORE specific (1-20) 2 ARATH/CRY1 GO:1902347 response to strigolactone ARBA:ARBA00089248 KEEP_AS_NON_CORE specific (1-20) 1 ARATH/CRY1 GO:2000377 regulation of reactive oxygen species metabolic process ARBA:ARBA00086857 KEEP_AS_NON_CORE specific (1-20) 20 ARATH/CRY1 GO:0005737 cytoplasm ARBA:ARBA00026971 ACCEPT very general (>200 descendants) 1146 ARATH/CRY1 GO:0016604 nuclear body ARBA:ARBA00043611 ACCEPT specific (1-20) 16 ARATH/CRY2 GO:0005524 ATP binding ARBA:ARBA00027027 KEEP_AS_NON_CORE leaf (0) 0 ARATH/CRY2 GO:0042803 protein homodimerization activity ARBA:ARBA00027933 KEEP_AS_NON_CORE leaf (0) 0 ARATH/CRY2 GO:0071949 FAD binding ARBA:ARBA00084586 KEEP_AS_NON_CORE leaf (0) 0 ARATH/CRY2 GO:0009414 response to water deprivation ARBA:ARBA00028094 KEEP_AS_NON_CORE specific (1-20) 7 ARATH/CRY2 GO:0009638 phototropism ARBA:ARBA00091921 KEEP_AS_NON_CORE leaf (0) 0 ARATH/CRY2 GO:0009646 response to absence of light ARBA:ARBA00091861 KEEP_AS_NON_CORE specific (1-20) 3 ARATH/CRY2 GO:0009785 blue light signaling pathway ARBA:ARBA00028968 ACCEPT specific (1-20) 1 ARATH/CRY2 GO:0009791 post-embryonic development ARBA:ARBA00029007 MARK_AS_OVER_ANNOTATED very general (>200 descendants) 271 TOO_GENERAL true but uninformative broad Post-embryonic development is a broad phenotypic umbrella. More specific CRY2 annotations to blue-light signaling, flowering, phototropism, and low-blue-light growth are preferable. ARATH/CRY2 GO:0010075 regulation of meristem growth ARBA:ARBA00091443 KEEP_AS_NON_CORE specific (1-20) 5 ARATH/CRY2 GO:0010118 stomatal movement ARBA:ARBA00090909 KEEP_AS_NON_CORE specific (1-20) 3 ARATH/CRY2 GO:0010244 response to low fluence blue light stimulus by blue low-fluence system ARBA:ARBA00090587 ACCEPT leaf (0) 0 ARATH/CRY2 GO:0010617 circadian regulation of calcium ion oscillation ARBA:ARBA00091901 KEEP_AS_NON_CORE leaf (0) 0 ARATH/CRY2 GO:0042752 regulation of circadian rhythm ARBA:ARBA00088520 KEEP_AS_NON_CORE general (21-200) 21 ARATH/CRY2 GO:0048580 regulation of post-embryonic development ARBA:ARBA00043383 MARK_AS_OVER_ANNOTATED general (21-200) 51 TOO_GENERAL true but uninformative broad CRY2 regulates specific light-responsive developmental outputs; broad regulation of post-embryonic development is less informative than blue-light signaling and flowering terms. ARATH/CRY2 GO:0048731 system development ARBA:ARBA00027702 MARK_AS_OVER_ANNOTATED very general (>200 descendants) 2438 UNCLASSIFIED unclassified System development does not capture the CRY2 mechanism and should not be used when specific light signaling and flowering annotations are available. ARATH/CRY2 GO:0072387 flavin adenine dinucleotide metabolic process ARBA:ARBA00090789 MODIFY specific (1-20) 4 OTHER_TERM different term needed replacement term The evidence concerns FAD redox photochemistry and light sensitivity, not FAD biosynthesis, catabolism, or metabolism. Replace with FAD binding and blue-light photoreceptor activity. ARATH/CRY2 GO:1901371 regulation of leaf morphogenesis ARBA:ARBA00092524 KEEP_AS_NON_CORE specific (1-20) 2 ARATH/CRY2 GO:1902347 response to strigolactone ARBA:ARBA00089248 KEEP_AS_NON_CORE specific (1-20) 1 ARATH/CRY2 GO:2000377 regulation of reactive oxygen species metabolic process ARBA:ARBA00086857 KEEP_AS_NON_CORE specific (1-20) 20 ARATH/CRY2 GO:0005737 cytoplasm ARBA:ARBA00026971 KEEP_AS_NON_CORE very general (>200 descendants) 1146 ARATH/CRY2 GO:0016604 nuclear body ARBA:ARBA00043611 ACCEPT specific (1-20) 16 ARATH/CUT1 GO:0005783 endoplasmic reticulum ARBA:ARBA00028672 ACCEPT general (21-200) 100 ARATH/CYCD6-1 GO:0010440 stomatal lineage progression ARBA:ARBA00092641 REMOVE specific (1-20) 3 WRONG_PARALOG wrong manual WRONG_PARALOG No evidence links CYCD6;1 to the stomatal lineage; its expression and function are confined to root ground-tissue formative divisions and lateral root primordia. This appears to be an over-propagation of a D-type cyclin rule. ARATH/DCL1 GO:0009616 RNAi-mediated antiviral immune response ARBA:ARBA00095379 KEEP_AS_NON_CORE specific (1-20) 2 ARATH/DCL1 GO:0010267 ta-siRNA processing ARBA:ARBA00090672 KEEP_AS_NON_CORE leaf (0) 0 ARATH/DCL1 GO:0035196 miRNA processing ARBA:ARBA00028690 MODIFY specific (1-20) 4 NEEDS_MORE_SPECIFIC true but uninformative replacement term The more precise process term for DCL1 is primary miRNA processing. ARATH/DRB1 GO:0003725 double-stranded RNA binding ARBA:ARBA00028403 ACCEPT specific (1-20) 2 ARATH/EBF1 GO:0006511 ubiquitin-dependent protein catabolic process ARBA:ARBA00026385 ACCEPT specific (1-20) 18 ARATH/EBF1 GO:0009723 response to ethylene ARBA:ARBA00028729 ACCEPT specific (1-20) 7 ARATH/EBF1 GO:0010105 negative regulation of ethylene-activated signaling pathway ARBA:ARBA00027582 ACCEPT leaf (0) 0 ARATH/EBF2 GO:0006511 ubiquitin-dependent protein catabolic process ARBA:ARBA00026385 ACCEPT specific (1-20) 18 ARATH/EBF2 GO:0009723 response to ethylene ARBA:ARBA00028729 ACCEPT specific (1-20) 7 ARATH/EBF2 GO:0010105 negative regulation of ethylene-activated signaling pathway ARBA:ARBA00027582 ACCEPT leaf (0) 0 ARATH/EFR GO:0009617 response to bacterium ARBA:ARBA00026494 KEEP_AS_NON_CORE general (21-200) 53 ARATH/EFR GO:0031349 positive regulation of defense response ARBA:ARBA00028260 ACCEPT general (21-200) 156 ARATH/EGL3 GO:0009867 jasmonic acid mediated signaling pathway ARBA:ARBA00033508 KEEP_AS_NON_CORE specific (1-20) 2 ARATH/EGL3 GO:0010026 trichome differentiation ARBA:ARBA00091409 ACCEPT specific (1-20) 9 ARATH/EGL3 GO:0090628 plant epidermal cell fate specification ARBA:ARBA00095292 ACCEPT specific (1-20) 2 ARATH/EIL1 GO:0000976 transcription cis-regulatory region binding ARBA:ARBA00028970 ACCEPT general (21-200) 32 ARATH/EIL1 GO:0009873 ethylene-activated signaling pathway ARBA:ARBA00084995 ACCEPT specific (1-20) 4 ARATH/EPF2 GO:0160109 plant gross anatomical part developmental process ARBA:ARBA00098140 KEEP_AS_NON_CORE very general (>200 descendants) 262 ARATH/ERECTA GO:0010103 stomatal complex morphogenesis ARBA:ARBA00090926 MODIFY specific (1-20) 5 OTHER_TERM different term needed replacement term ERECTA's role in the stomatal lineage is as the EPF2 receptor that inhibits stomatal lineage entry and, with its paralogs, enforces stomatal patterning; 'morphogenesis' mis-describes this regulatory role. ARATH/ERECTA GO:0048827 phyllome development ARBA:ARBA00034933 KEEP_AS_NON_CORE general (21-200) 61 ARATH/ERECTA GO:0090567 reproductive shoot system development ARBA:ARBA00028307 KEEP_AS_NON_CORE general (21-200) 74 ARATH/ERS1 GO:0005783 endoplasmic reticulum ARBA:ARBA00028672 ACCEPT general (21-200) 100 ARATH/ERS1 GO:0010105 negative regulation of ethylene-activated signaling pathway ARBA:ARBA00027582 ACCEPT leaf (0) 0 ARATH/ERS1 GO:0051740 ethylene binding ARBA:ARBA00027894 ACCEPT leaf (0) 0 ARATH/ESP GO:0019762 glucosinolate catabolic process ARBA:ARBA00043525 ACCEPT specific (1-20) 1 ARATH/ESP GO:0080028 nitrile biosynthetic process ARBA:ARBA00043356 ACCEPT specific (1-20) 4 ARATH/ETR1 GO:0005783 endoplasmic reticulum ARBA:ARBA00028672 ACCEPT general (21-200) 100 ARATH/ETR1 GO:0010105 negative regulation of ethylene-activated signaling pathway ARBA:ARBA00027582 ACCEPT leaf (0) 0 ARATH/FAE1 GO:0005783 endoplasmic reticulum ARBA:ARBA00028672 ACCEPT general (21-200) 100 ARATH/FAMA GO:0006355 regulation of DNA-templated transcription ARBA:ARBA00028138 ACCEPT general (21-200) 140 ARATH/FCA GO:0009909 regulation of flower development ARBA:ARBA00043323 ACCEPT specific (1-20) 2 ARATH/FIE GO:0040029 epigenetic regulation of gene expression ARBA:ARBA00033485 ACCEPT general (21-200) 44 ARATH/FKF1 GO:0006511 ubiquitin-dependent protein catabolic process ARBA:ARBA00026385 ACCEPT specific (1-20) 18 ARATH/FKF1 GO:0007623 circadian rhythm ARBA:ARBA00027901 KEEP_AS_NON_CORE specific (1-20) 19 ARATH/FKF1 GO:0009637 response to blue light ARBA:ARBA00026676 ACCEPT specific (1-20) 7 ARATH/FLC GO:0009909 regulation of flower development ARBA:ARBA00043323 ACCEPT specific (1-20) 2 ARATH/FLS2 GO:0007165 signal transduction ARBA:ARBA00029050 MODIFY very general (>200 descendants) 937 NEEDS_MORE_SPECIFIC true but uninformative replacement term The specific FLS2 process is pathogen-associated molecular pattern receptor signaling. ARATH/FLS2 GO:0071555 cell wall organization ARBA:ARBA00027619 MODIFY general (21-200) 38 NEEDS_MORE_SPECIFIC true but uninformative replacement term A defense-specific callose deposition term is more accurate than broad cell wall organization. ARATH/FLS2 GO:0071944 cell periphery ARBA:ARBA00027443 MODIFY very general (>200 descendants) 493 NEEDS_MORE_SPECIFIC true but uninformative replacement term Plasma membrane is the more precise cellular-component term for FLS2. ARATH/FTSH12 GO:0005737 cytoplasm ARBA:ARBA00026971 MODIFY very general (>200 descendants) 1146 NEEDS_MORE_SPECIFIC true but uninformative replacement term Cytoplasm is imprecise for the demonstrated chloroplast inner-envelope compartment. The exact sequence preserves the reference chloroplast targeting peptide and membrane segments, supporting a specific inner-envelope location. ARATH/FVE GO:0006355 regulation of DNA-templated transcription ARBA:ARBA00028138 ACCEPT general (21-200) 140 ARATH/FVE GO:0010629 negative regulation of gene expression ARBA:ARBA00026647 ACCEPT very general (>200 descendants) 274 ARATH/FVE GO:0035098 ESC/E(Z) complex ARBA:ARBA00089504 ACCEPT leaf (0) 0 ARATH/FVE GO:0040029 epigenetic regulation of gene expression ARBA:ARBA00033485 ACCEPT general (21-200) 44 ARATH/GA1 GO:0003824 catalytic activity ARBA:ARBA00027533 MODIFY very general (>200 descendants) 6405 NEEDS_MORE_SPECIFIC true but uninformative replacement term Correct but uninformative; the specific activity (ent-copalyl diphosphate synthase, EC 5.5.1.13, RHEA:14841) is experimentally established. ARATH/GAI GO:0009740 gibberellic acid mediated signaling pathway ARBA:ARBA00028868 ACCEPT specific (1-20) 2 ARATH/GGP1 GO:0008233 peptidase activity ARBA:ARBA00027408 MODIFY general (21-200) 81 NEEDS_MORE_SPECIFIC true but uninformative replacement term GGP1 is a peptidase C26-family hydrolase whose demonstrated activity is specifically gamma-glutamyl isopeptide bond cleavage; for consistency with the IDA row, the informative child term GO:0034722 is proposed. ARATH/GGP1 GO:0019760 glucosinolate metabolic process ARBA:ARBA00043526 MODIFY specific (1-20) 6 NEEDS_MORE_SPECIFIC true but uninformative replacement term GGP1 catalyzes a biosynthetic step, so the child term glucosinolate biosynthetic process is proposed, consistent with the experimental rows. ARATH/GID1A GO:0009939 positive regulation of gibberellic acid mediated signaling pathway ARBA:ARBA00084445 ACCEPT leaf (0) 0 ARATH/GID1A GO:0048444 floral organ morphogenesis ARBA:ARBA00089680 KEEP_AS_NON_CORE general (21-200) 27 ARATH/GID1A GO:0048530 fruit morphogenesis ARBA:ARBA00091695 KEEP_AS_NON_CORE leaf (0) 0 ARATH/GID1B GO:0048530 fruit morphogenesis ARBA:ARBA00091695 KEEP_AS_NON_CORE leaf (0) 0 ARATH/GID1C GO:0048530 fruit morphogenesis ARBA:ARBA00091695 KEEP_AS_NON_CORE leaf (0) 0 ARATH/GL1 GO:0003677 DNA binding ARBA:ARBA00029224 MODIFY general (21-200) 130 NEEDS_MORE_SPECIFIC true but uninformative replacement term Use transcription cis-regulatory region binding to capture promoter/regulatory DNA binding by the transcription factor. ARATH/GL1 GO:0030154 cell differentiation ARBA:ARBA00027429 MODIFY very general (>200 descendants) 1345 NEEDS_MORE_SPECIFIC true but uninformative replacement term Plant epidermal cell fate specification is the more informative supported process. ARATH/GL1 GO:0048731 system development ARBA:ARBA00027702 MODIFY very general (>200 descendants) 2438 OTHER_TERM different term needed replacement term Narrow the electronic development assignment to the experimentally supported trichome differentiation process. ARATH/GL1 GO:0090558 plant epidermis development ARBA:ARBA00047265 ACCEPT general (21-200) 34 ARATH/GL2 GO:0030154 cell differentiation ARBA:ARBA00027429 MODIFY very general (>200 descendants) 1345 NEEDS_MORE_SPECIFIC true but uninformative replacement term Plant epidermal cell fate specification is the more informative supported process. ARATH/GL3 GO:0009867 jasmonic acid mediated signaling pathway ARBA:ARBA00033508 KEEP_AS_NON_CORE specific (1-20) 2 ARATH/GL3 GO:0010026 trichome differentiation ARBA:ARBA00091409 ACCEPT specific (1-20) 9 ARATH/GL3 GO:0090628 plant epidermal cell fate specification ARBA:ARBA00095292 ACCEPT specific (1-20) 2 ARATH/GL3 GO:0005634 nucleus ARBA:ARBA00026330 ACCEPT very general (>200 descendants) 473 ARATH/GSTF11 GO:0009407 toxin catabolic process ARBA:ARBA00028091 KEEP_AS_NON_CORE specific (1-20) 12 ARATH/GSTU20 GO:0009407 toxin catabolic process ARBA:ARBA00028091 KEEP_AS_NON_CORE specific (1-20) 12 ARATH/HEN1 GO:0016070 RNA metabolic process ARBA:ARBA00028985 MODIFY very general (>200 descendants) 507 NEEDS_MORE_SPECIFIC true but uninformative replacement term RNA metabolic process is too broad; small-RNA methylation and miRNA/siRNA processing-stabilization outputs are more informative. ARATH/HKT1 GO:0006813 potassium ion transport ARBA:ARBA00028465 MARK_AS_OVER_ANNOTATED general (21-200) 45 INDIRECT_EFFECT overreach indirect "This is a family/name-derived electronic inference. The Arabidopsis protein is Na+-selective and does not transport K+ in planta; UniProt states it ""Does not transport K(+)"". The K+-related function is at most an indirect consequence of Na+ homeostasis, so direct K+ transport is an over-annotation rather than the gene's activity." ARATH/HKT1 GO:0046873 metal ion transmembrane transporter activity ARBA:ARBA00028200 MODIFY very general (>200 descendants) 204 NEEDS_MORE_SPECIFIC true but uninformative replacement term Correct (Na+ is a metal ion) but too general. The specific, experimentally supported molecular function is sodium ion transmembrane transporter activity. ARATH/HSP17.6A GO:0006950 response to stress ARBA:ARBA00026300 KEEP_AS_NON_CORE very general (>200 descendants) 590 ARATH/HSP17.7 GO:0006950 response to stress ARBA:ARBA00026300 ACCEPT very general (>200 descendants) 590 ARATH/ICS1 GO:0009536 plastid ARBA:ARBA00027316 ACCEPT general (21-200) 124 ARATH/ICS1 GO:0042372 phylloquinone biosynthetic process ARBA:ARBA00087584 KEEP_AS_NON_CORE leaf (0) 0 ARATH/JKD GO:0006355 regulation of DNA-templated transcription ARBA:ARBA00028138 ACCEPT general (21-200) 140 ARATH/KAO1 GO:0005783 endoplasmic reticulum ARBA:ARBA00028672 ACCEPT general (21-200) 100 ARATH/KAO2 GO:0005783 endoplasmic reticulum ARBA:ARBA00028672 ACCEPT general (21-200) 100 ARATH/KCR1 GO:0005783 endoplasmic reticulum ARBA:ARBA00028672 ACCEPT general (21-200) 100 ARATH/KCR1 GO:0016616 oxidoreductase activity, acting on the CH-OH group of donors, NAD or NADP as acceptor ARBA:ARBA00028442 ACCEPT very general (>200 descendants) 364 ARATH/LCYB GO:0009975 cyclase activity ARBA:ARBA00027212 MODIFY general (21-200) 23 NEEDS_MORE_SPECIFIC true but uninformative replacement term Correct but uninformatively broad. GO:0009975 is a verified is_a ancestor of the specific, experimentally supported molecular function GO:0045436 lycopene beta cyclase activity (EC 5.5.1.19), which is the appropriate replacement. ARATH/LCYB GO:0016860 intramolecular oxidoreductase activity ARBA:ARBA00026964 MODIFY general (21-200) 67 NEEDS_MORE_SPECIFIC true but uninformative replacement term Correct but uninformatively broad. GO:0016860 is a verified is_a ancestor of the specific molecular function GO:0045436 lycopene beta cyclase activity (the lycopene cyclase belongs to the isomerase/intramolecular-lyase branch). Replace with the specific, experimentally supported term. ARATH/LCYE GO:0009975 cyclase activity ARBA:ARBA00027212 MODIFY general (21-200) 23 NEEDS_MORE_SPECIFIC true but uninformative replacement term The gene has a precise, experimentally established molecular function, lycopene epsilon cyclase activity (GO:0045435, EC 5.5.1.18), which is the appropriate specific replacement for the generic 'cyclase activity'. ARATH/LCYE GO:0016860 intramolecular oxidoreductase activity ARBA:ARBA00026964 MODIFY general (21-200) 67 NEEDS_MORE_SPECIFIC true but uninformative replacement term Correct branch but too general. The specific, experimentally supported molecular function is lycopene epsilon cyclase activity (GO:0045435, EC 5.5.1.18), which is the appropriate replacement. Not removed, because GO:0016860 genuinely subsumes the specific term in the current ontology. ARATH/LFY GO:0010074 maintenance of meristem identity ARBA:ARBA00091440 MODIFY specific (1-20) 5 OTHER_TERM different term needed replacement term The evidence for LFY supports floral meristem fate/determinacy and regulation of flower development. A floral-meristem-specific term is more accurate than the broad maintenance term. ARATH/LHP1 GO:0000792 heterochromatin ARBA:ARBA00027530 KEEP_AS_NON_CORE specific (1-20) 14 ARATH/LHP1 GO:0010468 regulation of gene expression ARBA:ARBA00028334 MODIFY very general (>200 descendants) 874 NEEDS_MORE_SPECIFIC true but uninformative replacement term Correct but too general; LHP1 mediates epigenetic (Polycomb/H3K27me3) repression of gene expression, already annotated by IMP and IBA. ARATH/LHY GO:0010468 regulation of gene expression ARBA:ARBA00028334 KEEP_AS_NON_CORE very general (>200 descendants) 874 ARATH/MAM1 GO:0019761 glucosinolate biosynthetic process ARBA:ARBA00085760 ACCEPT specific (1-20) 2 ARATH/MAM3 GO:0019761 glucosinolate biosynthetic process ARBA:ARBA00085760 ACCEPT specific (1-20) 2 ARATH/MAX2 GO:0000151 ubiquitin ligase complex ARBA:ARBA00029181 MODIFY general (21-200) 52 NEEDS_MORE_SPECIFIC true but uninformative replacement term Correct but less specific than the experimentally supported SCF ubiquitin ligase complex. ARATH/MAX2 GO:0006511 ubiquitin-dependent protein catabolic process ARBA:ARBA00026385 MODIFY specific (1-20) 18 NEEDS_MORE_SPECIFIC true but uninformative replacement term Correct; the more specific SCF-dependent proteasomal ubiquitin-dependent protein catabolic process is supported for MAX2 (SMXL6/7/8 degradation). ARATH/MAX2 GO:0009653 anatomical structure morphogenesis ARBA:ARBA00026583 MARK_AS_OVER_ANNOTATED very general (>200 descendants) 1501 INDIRECT_EFFECT overreach downstream Very general developmental term; MAX2 effects on morphology are downstream outputs of SL and KAI2-ligand signalling and are better captured by specific terms. Unlike the ARBA regulation of developmental process row (MODIFY to regulation of secondary shoot formation), this is a non-regulatory process term whose descendants describe performing morphogenesis, which MAX2 does not do, so there is no apt narrower replacement. ARATH/MAX2 GO:0050793 regulation of developmental process ARBA:ARBA00028689 MODIFY very general (>200 descendants) 1542 NEEDS_MORE_SPECIFIC true but uninformative replacement term Too general; the best-characterised developmental role of MAX2 is control of shoot branching. Being a regulation term, it has an apt regulatory descendant (unlike the ARBA anatomical structure morphogenesis row, which is marked over-annotated instead). ARATH/MGP GO:0006355 regulation of DNA-templated transcription ARBA:ARBA00028138 ACCEPT general (21-200) 140 ARATH/MKK4 GO:0007165 signal transduction ARBA:ARBA00029050 ACCEPT very general (>200 descendants) 937 ARATH/MKK4 GO:0010227 floral organ abscission ARBA:ARBA00026833 KEEP_AS_NON_CORE leaf (0) 0 ARATH/MKK4 GO:0010229 inflorescence development ARBA:ARBA00090608 KEEP_AS_NON_CORE specific (1-20) 4 ARATH/MKK4 GO:0098542 defense response to other organism ARBA:ARBA00027395 ACCEPT general (21-200) 77 ARATH/MKK5 GO:0005737 cytoplasm ARBA:ARBA00026971 ACCEPT very general (>200 descendants) 1146 ARATH/MKK5 GO:0007165 signal transduction ARBA:ARBA00029050 ACCEPT very general (>200 descendants) 937 ARATH/MKK5 GO:0010227 floral organ abscission ARBA:ARBA00026833 KEEP_AS_NON_CORE leaf (0) 0 ARATH/MKK5 GO:0010229 inflorescence development ARBA:ARBA00090608 KEEP_AS_NON_CORE specific (1-20) 4 ARATH/MKK5 GO:0098542 defense response to other organism ARBA:ARBA00027395 ACCEPT general (21-200) 77 ARATH/MPK6 GO:0007165 signal transduction ARBA:ARBA00029050 ACCEPT very general (>200 descendants) 937 ARATH/MYB122 GO:0000976 transcription cis-regulatory region binding ARBA:ARBA00028970 ACCEPT general (21-200) 32 ARATH/MYB122 GO:0006950 response to stress ARBA:ARBA00026300 KEEP_AS_NON_CORE very general (>200 descendants) 590 ARATH/MYB122 GO:0051707 response to other organism ARBA:ARBA00029118 KEEP_AS_NON_CORE general (21-200) 199 ARATH/MYB34 GO:0000976 transcription cis-regulatory region binding ARBA:ARBA00028970 ACCEPT general (21-200) 32 ARATH/MYB34 GO:0006950 response to stress ARBA:ARBA00026300 KEEP_AS_NON_CORE very general (>200 descendants) 590 ARATH/MYB34 GO:0051707 response to other organism ARBA:ARBA00029118 KEEP_AS_NON_CORE general (21-200) 199 ARATH/MYC2 GO:0010468 regulation of gene expression ARBA:ARBA00028334 MODIFY very general (>200 descendants) 874 NEEDS_MORE_SPECIFIC true but uninformative replacement term The domain/family-based inference is independently corroborated by MYC2 DNA-binding and promoter-transactivation experiments in PMID:9368419 and PMID:21321051. Refine generic regulation of gene expression to transcriptional regulation. ARATH/MYC2 GO:0005634 nucleus ARBA:ARBA00026330 ACCEPT very general (>200 descendants) 473 ARATH/NPR1 GO:0031347 regulation of defense response ARBA:ARBA00028262 ACCEPT very general (>200 descendants) 366 ARATH/NPR1 GO:0045087 innate immune response ARBA:ARBA00027946 ACCEPT general (21-200) 39 ARATH/NSP1 GO:0009845 seed germination ARBA:ARBA00084883 UNDECIDED specific (1-20) 2 ARATH/OST1 GO:0009414 response to water deprivation ARBA:ARBA00028094 ACCEPT specific (1-20) 7 ARATH/OST1 GO:0009651 response to salt stress ARBA:ARBA00026582 KEEP_AS_NON_CORE specific (1-20) 8 ARATH/OST1 GO:0009737 response to abscisic acid ARBA:ARBA00033526 ACCEPT specific (1-20) 5 ARATH/PAL1 GO:0006952 defense response ARBA:ARBA00026315 KEEP_AS_NON_CORE general (21-200) 175 ARATH/PAL1 GO:0006979 response to oxidative stress ARBA:ARBA00026273 KEEP_AS_NON_CORE general (21-200) 42 ARATH/PAL1 GO:0009611 response to wounding ARBA:ARBA00026469 KEEP_AS_NON_CORE general (21-200) 40 ARATH/PAL1 GO:0009698 phenylpropanoid metabolic process ARBA:ARBA00026696 ACCEPT general (21-200) 60 ARATH/PAL1 GO:0046395 carboxylic acid catabolic process ARBA:ARBA00027882 MARK_AS_OVER_ANNOTATED general (21-200) 174 TOO_GENERAL true but uninformative general Overly general parent of GO:0006559; the more specific catabolic/metabolic process terms better describe the function. Not wrong, but redundant and uninformative. ARATH/PDS GO:0016120 carotene biosynthetic process ARBA:ARBA00028053 ACCEPT specific (1-20) 7 ARATH/PHYA GO:0042802 identical protein binding ARBA:ARBA00027930 MODIFY specific (1-20) 1 NEEDS_MORE_SPECIFIC true but uninformative replacement term Use the more informative homodimerization term. ARATH/PHYB GO:0042802 identical protein binding ARBA:ARBA00027930 ACCEPT specific (1-20) 1 ARATH/PI GO:0010093 specification of floral organ identity ARBA:ARBA00090791 ACCEPT specific (1-20) 4 ARATH/PID GO:0048825 cotyledon development ARBA:ARBA00090556 KEEP_AS_NON_CORE specific (1-20) 2 ARATH/PIF1 GO:0010017 red or far-red light signaling pathway ARBA:ARBA00044396 ACCEPT specific (1-20) 6 ARATH/PIF3 GO:0010017 red or far-red light signaling pathway ARBA:ARBA00044396 ACCEPT specific (1-20) 6 ARATH/PIF4 GO:0010017 red or far-red light signaling pathway ARBA:ARBA00044396 ACCEPT specific (1-20) 6 ARATH/PIN1 GO:0060918 auxin transport ARBA:ARBA00026839 ACCEPT specific (1-20) 11 ARATH/PIN2 GO:0060918 auxin transport ARBA:ARBA00026839 ACCEPT specific (1-20) 11 ARATH/PRR5 GO:0007623 circadian rhythm ARBA:ARBA00027901 ACCEPT specific (1-20) 19 ARATH/PRR7 GO:0007623 circadian rhythm ARBA:ARBA00027901 ACCEPT specific (1-20) 19 ARATH/PRR9 GO:0007623 circadian rhythm ARBA:ARBA00027901 ACCEPT specific (1-20) 19 ARATH/PYR1 GO:0004864 protein phosphatase inhibitor activity ARBA:ARBA00027010 ACCEPT specific (1-20) 1 ARATH/PYR1 GO:0009738 abscisic acid-activated signaling pathway ARBA:ARBA00085216 ACCEPT specific (1-20) 1 ARATH/PYR1 GO:0038023 signaling receptor activity ARBA:ARBA00027254 ACCEPT very general (>200 descendants) 389 ARATH/PYR1 GO:0042803 protein homodimerization activity ARBA:ARBA00027933 ACCEPT leaf (0) 0 ARATH/RBOHD GO:0006952 defense response ARBA:ARBA00026315 ACCEPT general (21-200) 175 ARATH/RDR6 GO:0031047 regulatory ncRNA-mediated gene silencing ARBA:ARBA00027536 ACCEPT general (21-200) 51 ARATH/RGA GO:0009740 gibberellic acid mediated signaling pathway ARBA:ARBA00028868 ACCEPT specific (1-20) 2 ARATH/RPM1 GO:0009626 plant-type hypersensitive response ARBA:ARBA00091908 ACCEPT leaf (0) 0 ARATH/RPM1 GO:0005886 plasma membrane ARBA:ARBA00027801 ACCEPT very general (>200 descendants) 415 ARATH/SEP1 GO:0048440 carpel development ARBA:ARBA00089672 KEEP_AS_NON_CORE specific (1-20) 12 ARATH/SEP2 GO:0048440 carpel development ARBA:ARBA00089672 KEEP_AS_NON_CORE specific (1-20) 12 ARATH/SEP3 GO:0005634 nucleus ARBA:ARBA00026330 ACCEPT very general (>200 descendants) 473 ARATH/SEP4 GO:0048440 carpel development ARBA:ARBA00089672 KEEP_AS_NON_CORE specific (1-20) 12 ARATH/SIZ1 GO:0019789 SUMO transferase activity ARBA:ARBA00027358 ACCEPT specific (1-20) 3 ARATH/SMXL8 GO:1902347 response to strigolactone ARBA:ARBA00089248 KEEP_AS_NON_CORE specific (1-20) 1 ARATH/SOC1 GO:0050793 regulation of developmental process ARBA:ARBA00028689 MODIFY very general (>200 descendants) 1542 OTHER_TERM different term needed replacement term Replace with vegetative to reproductive phase transition of meristem, the specific developmental process repeatedly supported by SOC1 genetics and expression. ARATH/SPA1 GO:0042802 identical protein binding ARBA:ARBA00027930 KEEP_AS_NON_CORE specific (1-20) 1 ARATH/SPCH GO:0006355 regulation of DNA-templated transcription ARBA:ARBA00028138 KEEP_AS_NON_CORE general (21-200) 140 ARATH/SSU3 GO:0019761 glucosinolate biosynthetic process ARBA:ARBA00085760 ACCEPT specific (1-20) 2 ARATH/STM GO:0003676 nucleic acid binding ARBA:ARBA00029220 MODIFY very general (>200 descendants) 299 NEEDS_MORE_SPECIFIC true but uninformative replacement term Replace the generic parent term with specific regulatory DNA-binding and RNA polymerase II transcription factor terms. ARATH/STM GO:0009888 tissue development ARBA:ARBA00028065 MODIFY very general (>200 descendants) 1023 OTHER_TERM different term needed replacement term Replace the broad ARBA term with more specific existing STM terms rather than retaining a vague developmental parent. ARATH/SUN1 GO:0006997 nucleus organization ARBA:ARBA00033484 ACCEPT general (21-200) 61 ARATH/SUN1 GO:0043495 protein-membrane adaptor activity ARBA:ARBA00085899 ACCEPT specific (1-20) 12 ARATH/SUN1 GO:0051260 protein homooligomerization ARBA:ARBA00089314 KEEP_AS_NON_CORE specific (1-20) 2 ARATH/SUN1 GO:0051291 protein heterooligomerization ARBA:ARBA00089325 KEEP_AS_NON_CORE specific (1-20) 2 ARATH/SUN1 GO:0070197 meiotic attachment of telomere to nuclear envelope ARBA:ARBA00092228 ACCEPT leaf (0) 0 ARATH/SUN1 GO:0090435 protein localization to nuclear envelope ARBA:ARBA00088559 ACCEPT specific (1-20) 2 ARATH/SUN2 GO:0006997 nucleus organization ARBA:ARBA00033484 ACCEPT general (21-200) 61 ARATH/SUN2 GO:0043495 protein-membrane adaptor activity ARBA:ARBA00085899 ACCEPT specific (1-20) 12 ARATH/SUN2 GO:0051260 protein homooligomerization ARBA:ARBA00089314 KEEP_AS_NON_CORE specific (1-20) 2 ARATH/SUN2 GO:0051291 protein heterooligomerization ARBA:ARBA00089325 KEEP_AS_NON_CORE specific (1-20) 2 ARATH/SUN2 GO:0070197 meiotic attachment of telomere to nuclear envelope ARBA:ARBA00092228 ACCEPT leaf (0) 0 ARATH/SUN2 GO:0090435 protein localization to nuclear envelope ARBA:ARBA00088559 ACCEPT specific (1-20) 2 ARATH/SWN GO:0050793 regulation of developmental process ARBA:ARBA00028689 ACCEPT very general (>200 descendants) 1542 ARATH/SWN GO:0141044 epigenetic programming in the endosperm ARBA:ARBA00095392 KEEP_AS_NON_CORE leaf (0) 0 ARATH/TMM GO:0016020 membrane ARBA:ARBA00028763 ACCEPT very general (>200 descendants) 895 ARATH/TOC1 GO:0007623 circadian rhythm ARBA:ARBA00027901 ACCEPT specific (1-20) 19 ARATH/TPL GO:0045892 negative regulation of DNA-templated transcription ARBA:ARBA00029084 ACCEPT general (21-200) 39 ARATH/TRY GO:0006355 regulation of DNA-templated transcription ARBA:ARBA00028138 ACCEPT general (21-200) 140 ARATH/TRY GO:0010026 trichome differentiation ARBA:ARBA00091409 KEEP_AS_NON_CORE specific (1-20) 9 ARATH/TRY GO:1900032 regulation of trichome patterning ARBA:ARBA00092511 ACCEPT specific (1-20) 1 ARATH/UGT74C1 GO:0035251 UDP-glucosyltransferase activity ARBA:ARBA00029194 MODIFY general (21-200) 78 NEEDS_MORE_SPECIFIC true but uninformative replacement term The annotation is sound but too general; UGT74C1 expresses thiohydroximate UGT activity in planta and complements ugt74b1, so the specific term GO:0047251 should be used. The comparator paralog UGT74B1 carries GO:0047251 by IDA. ARATH/VAL1 GO:0006355 regulation of DNA-templated transcription ARBA:ARBA00028138 MODIFY general (21-200) 140 NEEDS_MORE_SPECIFIC true but uninformative replacement term VAL1 is an active repressor; the negative regulation term is more accurate. ARATH/VRN1 GO:0009409 response to cold ARBA:ARBA00028088 ACCEPT specific (1-20) 5 ARATH/VRN2 GO:0006325 chromatin organization ARBA:ARBA00028060 ACCEPT very general (>200 descendants) 290 ARATH/ZTL GO:0006511 ubiquitin-dependent protein catabolic process ARBA:ARBA00026385 MODIFY specific (1-20) 18 NEEDS_MORE_SPECIFIC true but uninformative replacement term Direct experimental evidence shows ZTL controls proteasome-dependent degradation of TOC1 and PRR5. ZTL is the F-box substrate adaptor of SCF(ZTL), so the more specific child term SCF-dependent proteasomal ubiquitin-dependent protein catabolic process (GO:0031146), which ZTL already carries by IC and uses as its core process, is the appropriate term, as in the TIR1 and COI1 reviews. ARATH/ZTL GO:0007623 circadian rhythm ARBA:ARBA00027901 ACCEPT specific (1-20) 19 ARATH/ZTL GO:0009637 response to blue light ARBA:ARBA00026676 ACCEPT specific (1-20) 7 BACSU/ftsZ GO:0030428 cell septum ARBA:ARBA00087144 ACCEPT specific (1-20) 9 BACSU/minD GO:0032506 cytokinetic process ARBA:ARBA00028734 ACCEPT general (21-200) 36 BRADI/BRADI_1g66227v3 GO:0005794 Golgi apparatus ARBA:ARBA00028708 ACCEPT general (21-200) 48 BRADI/BRADI_1g66227v3 GO:0016020 membrane ARBA:ARBA00028763 KEEP_AS_NON_CORE very general (>200 descendants) 895 BRADI/LOC100829928 GO:0009699 phenylpropanoid biosynthetic process ARBA:ARBA00026697 ACCEPT general (21-200) 30 BURCH/A0B297 GO:0015749 monosaccharide transmembrane transport ARBA:ARBA00028498 ACCEPT general (21-200) 74 CAEBR/kin-1 GO:0004690 cyclic nucleotide-dependent protein kinase activity ARBA:ARBA00027143 MODIFY specific (1-20) 2 NEEDS_MORE_SPECIFIC true but uninformative replacement term Correct but one level too general: this protein is specifically a cAMP-dependent (not the broader cyclic nucleotide-dependent, which also encompasses cGMP-dependent) protein kinase. The more specific child term GO:0004691 is the appropriate function and is already annotated. CAEBR/tra-1 GO:0019099 female germ-line sex determination ARBA:ARBA00092111 KEEP_AS_NON_CORE leaf (0) 0 CAEBR/tra-1 GO:0019101 female somatic sex determination ARBA:ARBA00085316 KEEP_AS_NON_CORE leaf (0) 0 CANAL/BCY1 GO:0009267 cellular response to starvation ARBA:ARBA00034565 REMOVE general (21-200) 27 UNSUPPORTED overreach manual UNSUPPORTED Bcy1 controls PKA in nutrient and stress signaling, but this broad starvation response row is not supported by a specific Candida assay and does not capture Bcy1's direct work in the PKA holoenzyme. CANAL/BCY1 GO:0016020 membrane ARBA:ARBA00028763 REMOVE very general (>200 descendants) 895 WRONG_LOCATION wrong manual WRONG_LOCATION Bcy1 is not a generic membrane protein; it is soluble and mainly cytosolic. A conditional subpopulation is enriched around the vacuolar membrane during growth on glycerol, but that specific location is already covered by the direct Candida vacuolar-membrane IDA annotation. CANAL/CEK1 GO:0009272 fungal-type cell wall biogenesis ARBA:ARBA00033809 ACCEPT specific (1-20) 16 CANAL/ESA1 GO:0006974 DNA damage response ARBA:ARBA00026271 KEEP_AS_NON_CORE general (21-200) 95 CANAL/ESA1 GO:0046972 histone H4K16 acetyltransferase activity ARBA:ARBA00084756 KEEP_AS_NON_CORE leaf (0) 0 CANAL/GND1 GO:0016614 oxidoreductase activity, acting on CH-OH group of donors ARBA:ARBA00028437 MARK_AS_OVER_ANNOTATED very general (>200 descendants) 457 TOO_GENERAL true but uninformative Subsumed Subsumed by the specific, already-annotated GO:0004616; the grouping term adds no information about the actual reaction (oxidative decarboxylation of 6-phospho-D-gluconate). Treated the same way as the former keyword-derived GO:0016491 oxidoreductase activity row on this gene. Not wrong, so not removed. CANAL/HOG1 GO:0000165 MAPK cascade ARBA:ARBA00029221 MODIFY specific (1-20) 18 NEEDS_MORE_SPECIFIC true but uninformative replacement term Hog1 is specifically the terminal MAPK in the Ssk2-Pbs2-Hog1 stress-activated MAPK cascade, so GO:0051403 is the better biological-process term than the generic MAPK cascade ancestor. CANAL/HSP104 GO:0006457 protein folding ARBA:ARBA00027200 MODIFY specific (1-20) 7 NEEDS_MORE_SPECIFIC true but uninformative replacement term Hsp104-family disaggregases act after proteins have misfolded and aggregated; they solubilize aggregates so Hsp70/Hsp40 can refold the liberated clients. The C. albicans protein reactivates heat-denatured proteins in an S. cerevisiae hsp104 mutant, so GO:0042026 is the better process term. CANAL/HSP104 GO:0034605 cellular response to heat ARBA:ARBA00026567 ACCEPT specific (1-20) 3 CANAL/HSP104 GO:0043335 protein unfolding ARBA:ARBA00086271 ACCEPT leaf (0) 0 CANAL/HSP78 GO:0006457 protein folding ARBA:ARBA00027200 MODIFY specific (1-20) 7 NEEDS_MORE_SPECIFIC true but uninformative replacement term Hsp78 proteins act on preformed mitochondrial aggregates, resolubilizing them so clients can refold with Hsp70-system support. The exact descendant term is already asserted by PAINT at the fungal Hsp78 node. CAPO3/coWts GO:0007010 cytoskeleton organization ARBA:ARBA00026736 MARK_AS_OVER_ANNOTATED very general (>200 descendants) 224 INDIRECT_EFFECT overreach indirect coWts influences cytoskeletal behaviour, but indirectly: the phenotypes are attributed to derepressed coYki-dependent transcription, not to coWts acting on cytoskeletal structures. By the participation test, coWts does not do the work of assembling or arranging the cytoskeleton. Process terms describing the signalling role (hippo signaling) capture its function better. The F-actin, blebbistatin and latrunculin analyses were also performed in the coHpo mutant rather than coWts. CAPO3/coWts GO:0071944 cell periphery ARBA:ARBA00027443 UNDECIDED very general (>200 descendants) 493 CAPO3/coWts GO:1900181 negative regulation of protein localization to nucleus ARBA:ARBA00092942 ACCEPT specific (1-20) 3 COTJA/A0A8C2TBA7 GO:0001519 peptide amidation ARBA:ARBA00093736 ACCEPT leaf (0) 0 CRIGR/HSPH1 GO:0006950 response to stress ARBA:ARBA00026300 KEEP_AS_NON_CORE very general (>200 descendants) 590 CUCME/A0A1S3BTE3 GO:0007165 signal transduction ARBA:ARBA00029050 MARK_AS_OVER_ANNOTATED very general (>200 descendants) 937 TOO_GENERAL true but uninformative redundant The term is technically correct but redundant with the more specific GO:0000165 (MAPK cascade) annotation. The broad signal transduction term adds no specificity beyond what the MAPK cascade annotation already provides. DANRE/asah2 GO:0005737 cytoplasm ARBA:ARBA00026971 MARK_AS_OVER_ANNOTATED very general (>200 descendants) 1146 TOO_GENERAL true but uninformative uninformative Only the short N-terminal tail is cytosolic and no cytoplasmic pool of the enzyme has been reported; the term is not strictly false (mitochondrion is a descendant) but is uninformative and misleading for a plasma-membrane ceramidase. DANRE/asah2 GO:0006672 ceramide metabolic process ARBA:ARBA00028785 ACCEPT specific (1-20) 16 DANRE/cmpk GO:0050145 nucleoside monophosphate kinase activity ARBA:ARBA00033496 MODIFY specific (1-20) 4 NEEDS_MORE_SPECIFIC true but uninformative replacement term The enzyme has a defined preference for UMP and CMP with dCMP as a weaker substrate, so substrate-specific terms carry the information; the generic term is not wrong but adds nothing over them. DANRE/cpt2 GO:0005739 mitochondrion ARBA:ARBA00026962 KEEP_AS_NON_CORE general (21-200) 70 DANRE/cpt2 GO:0015909 long-chain fatty acid transport ARBA:ARBA00088749 KEEP_AS_NON_CORE specific (1-20) 10 DANRE/crppa GO:0009101 glycoprotein biosynthetic process ARBA:ARBA00027560 MODIFY general (21-200) 37 NEEDS_MORE_SPECIFIC true but uninformative replacement term GO:0035269 is a descendant of GO:0009101 and is the term supported by the biochemistry (CDP-ribitol donor for FKTN/FKRP ribitol-phosphate transfer to alpha-dystroglycan [PMID:27194101]) and by the zebrafish knockdown phenotype [PMID:22522421]. The broad term is not wrong, but the specific one is established and should be used. DANRE/cryaba GO:0005737 cytoplasm ARBA:ARBA00026971 ACCEPT very general (>200 descendants) 1146 DANRE/cryabb GO:0005198 structural molecule activity ARBA:ARBA00027476 MARK_AS_OVER_ANNOTATED general (21-200) 50 TOO_GENERAL true but uninformative generic The generic parent adds nothing beyond the InterPro-derived GO:0005212 child and is not what the protein has been shown to do; cryabb is a minor lens component whose defining activity is holdase chaperoning (PMID:16420472). Not wrong enough to remove, but over-broad and not a core function. DANRE/cryabb GO:0005737 cytoplasm ARBA:ARBA00026971 ACCEPT very general (>200 descendants) 1146 DANRE/cryabb GO:0043066 negative regulation of apoptotic process ARBA:ARBA00027746 KEEP_AS_NON_CORE general (21-200) 79 DANRE/cryabb GO:0005886 plasma membrane ARBA:ARBA00027801 REMOVE very general (>200 descendants) 415 WRONG_LOCATION wrong manual WRONG_LOCATION Nothing supports this location for cryabb: the protein is a soluble cytosolic sHSP recovered from the soluble lens proteome (PMID:16420472), and the ARBA rule that generated the row is a co-occurrence prediction rather than a localization observation. Removal does not deny transient membrane association reported for mammalian sHSPs under stress; it records that there is no evidence for this zebrafish protein. DANRE/ctdspl2a GO:0004721 phosphoprotein phosphatase activity ARBA:ARBA00027651 ACCEPT general (21-200) 36 DANRE/ctdspl2a GO:0005634 nucleus ARBA:ARBA00026330 ACCEPT very general (>200 descendants) 473 DANRE/ctdspl2a GO:0045722 positive regulation of gluconeogenesis ARBA:ARBA00084180 KEEP_AS_NON_CORE leaf (0) 0 DANRE/ctdspl2b GO:0004721 phosphoprotein phosphatase activity ARBA:ARBA00027651 ACCEPT general (21-200) 36 DANRE/ctdspl2b GO:0005634 nucleus ARBA:ARBA00026330 ACCEPT very general (>200 descendants) 473 DANRE/ctdspl2b GO:0045722 positive regulation of gluconeogenesis ARBA:ARBA00084180 KEEP_AS_NON_CORE leaf (0) 0 DANRE/cyp26a1 GO:0008401 retinoic acid 4-hydroxylase activity ARBA:ARBA00085214 ACCEPT specific (1-20) 1 DANRE/cyp26a1 GO:0034653 retinoic acid catabolic process ARBA:ARBA00049846 ACCEPT leaf (0) 0 DANRE/dcxr GO:0016616 oxidoreductase activity, acting on the CH-OH group of donors, NAD or NADP as acceptor ARBA:ARBA00028442 MODIFY very general (>200 descendants) 364 NEEDS_MORE_SPECIFIC true but uninformative replacement term The ARBA rule can only see that this is an SDR-fold NAD(P)-linked oxidoreductase acting on a CH-OH centre, which is correct as far as it goes. A specific child is supported on the same evidence that supports the IBA rows: the characterized reaction of the orthologs is the NADPH-dependent reduction of L-xylulose [PMID:11882650], and the zebrafish sequence retains the catalytic and cofactor-binding residues. Replace the class-level term with GO:0050038 rather than keeping a broad annotation alongside the specific one. DANRE/dla GO:0005737 cytoplasm ARBA:ARBA00026971 REMOVE very general (>200 descendants) 1146 WRONG_LOCATION wrong manual WRONG_LOCATION Dla immunolocalisation found punctate membrane/cortical staining and explicitly did not support broad cytoplasmic localisation; cytoplasm is not an appropriate location for this transmembrane ligand. DANRE/dla GO:0005886 plasma membrane ARBA:ARBA00027801 ACCEPT very general (>200 descendants) 415 DANRE/dla GO:0007389 pattern specification process ARBA:ARBA00027400 KEEP_AS_NON_CORE very general (>200 descendants) 307 DANRE/dla GO:0021514 ventral spinal cord interneuron differentiation ARBA:ARBA00084983 KEEP_AS_NON_CORE specific (1-20) 4 DANRE/dla GO:0043009 chordate embryonic development ARBA:ARBA00027425 MARK_AS_OVER_ANNOTATED general (21-200) 101 TOO_GENERAL true but uninformative Uninformative Uninformative high-level term; specific developmental roles are annotated. DANRE/dla GO:0048863 stem cell differentiation ARBA:ARBA00090702 MARK_AS_OVER_ANNOTATED general (21-200) 37 NO_EVIDENCE overreach no direct evidence Dla is expressed in adult proliferative zones, but there is no direct evidence that it regulates stem cell differentiation. DANRE/dla GO:0060485 mesenchyme development ARBA:ARBA00026415 REMOVE general (21-200) 92 UNSUPPORTED overreach manual UNSUPPORTED Transferred from mammalian Delta-like biology; in zebrafish, fin mesenchyme is present in deltaA mutants, and no evidence links Dla to mesenchyme development. DANRE/fgf8a GO:0007498 mesoderm development ARBA:ARBA00084318 KEEP_AS_NON_CORE general (21-200) 51 DANRE/fgf8a GO:0009952 anterior/posterior pattern specification ARBA:ARBA00027259 KEEP_AS_NON_CORE general (21-200) 74 DANRE/fgf8a GO:0042664 negative regulation of endodermal cell fate specification ARBA:ARBA00086809 KEEP_AS_NON_CORE leaf (0) 0 DANRE/fgf8b GO:0007498 mesoderm development ARBA:ARBA00084318 MARK_AS_OVER_ANNOTATED general (21-200) 51 WRONG_PARALOG wrong fgf8a The fgf8a evidence behind this kind of rule is gastrula-stage mesoderm formation (ace;oep interactions). fgf8b is not expressed during gastrulation and has no loss-of-function data; its somite expression begins at the 8-somite stage. The inference is not supported for fgf8b. Its paralogue fgf8a keeps this term. DANRE/fgf8b GO:0009952 anterior/posterior pattern specification ARBA:ARBA00027259 MARK_AS_OVER_ANNOTATED general (21-200) 74 WRONG_PARALOG wrong fgf8a No fgf8b-specific evidence. The fgf8a data for this term are from gastrula and early neural plate patterning, before fgf8b is expressed. DANRE/fgf8b GO:0042664 negative regulation of endodermal cell fate specification ARBA:ARBA00086809 REMOVE leaf (0) 0 WRONG_PARALOG wrong manual WRONG_PARALOG This is a blastula/gastrula process: FGF/ERK signalling limits Nodal-induced endoderm progenitors (PMID:16672336), a role of fgf8a. fgf8b is not expressed during gastrulation and there is no evidence that it acts in endoderm specification. The machine inference should not be carried to fgf8b. DANRE/flvcr2a GO:0015220 choline transmembrane transporter activity ARBA:ARBA00027949 ACCEPT specific (1-20) 2 DANRE/gnptab GO:0015031 protein transport ARBA:ARBA00026546 MODIFY general (21-200) 130 NEEDS_MORE_SPECIFIC true but uninformative replacement term GO:0015031 is an ancestor of GO:0016256 (QuickGO ancestor query), so the claim is not false, but the specific term that names the enzyme's own contribution - N-glycan processing to lysosome - is already annotated (IBA, IMP, ISS). Replace the generic ARBA term with GO:0016256 rather than keep a redundant, uninformative parent. DANRE/gria1a GO:0022824 transmitter-gated monoatomic ion channel activity ARBA:ARBA00028000 ACCEPT specific (1-20) 12 DANRE/gria1b GO:0022824 transmitter-gated monoatomic ion channel activity ARBA:ARBA00028000 ACCEPT specific (1-20) 12 DANRE/gtpbp3 GO:0070900 mitochondrial tRNA modification ARBA:ARBA00086089 ACCEPT specific (1-20) 6 DANRE/hif1an GO:0009966 regulation of signal transduction ARBA:ARBA00027204 KEEP_AS_NON_CORE very general (>200 descendants) 696 DANRE/hif1an GO:0050793 regulation of developmental process ARBA:ARBA00028689 KEEP_AS_NON_CORE very general (>200 descendants) 1542 DANRE/hsd17b3 GO:0008610 lipid biosynthetic process ARBA:ARBA00027236 MODIFY very general (>200 descendants) 258 NEEDS_MORE_SPECIFIC true but uninformative replacement term "Not wrong, but far too general to convey what Hsd17b3 does: the enzyme catalyzes a single 17beta-reduction that forms testosterone and 11-oxygenated testosterones from their 17-keto precursors [PMID:16216911 ""The zebrafish enzyme in vitro effectively catalyzed the conversion of androstenedione to testosterone""]. The specific descendants androgen biosynthetic process (GO:0006702, IDA) and testosterone biosynthetic process (GO:0061370) are already annotated and fully subsume this term; the ARBA row should be replaced by (or collapsed into) the androgen-biosynthesis annotation rather than kept as an uninformative parent." DANRE/hsd17b3 GO:0033764 steroid dehydrogenase activity, acting on the CH-OH group of donors, NAD or NADP as acceptor ARBA:ARBA00084320 MODIFY general (21-200) 30 NEEDS_MORE_SPECIFIC true but uninformative replacement term "Biochemically true (the enzyme is an NADP(H)-dependent steroid 17beta-dehydrogenase/reductase), but the exact reaction is experimentally established for the zebrafish protein and already annotated as testosterone dehydrogenase (NADP+) activity (GO:0047045) by IDA, IBA and EC mapping [PMID:16216911 ""The zebrafish enzyme in vitro effectively catalyzed the conversion of androstenedione to testosterone by use of NADPH as cofactor""]. The generic parent should be replaced by the specific child; retaining both adds no information. The enzyme's additional substrates (DHEA, epiandrosterone, 11-ketoandrostenedione, 11beta-hydroxyandrostenedione) are all 17beta-reductions of the same chemical class and are captured by UniProt's Rhea reactions rather than by this broad term." DANRE/kita GO:0030318 melanocyte differentiation ARBA:ARBA00087401 KEEP_AS_NON_CORE specific (1-20) 2 DANRE/kita GO:0097324 melanocyte migration ARBA:ARBA00089596 KEEP_AS_NON_CORE leaf (0) 0 DANRE/mfsd2aa GO:0051977 lysophospholipid transport ARBA:ARBA00089921 ACCEPT specific (1-20) 2 DANRE/notch1a GO:0007409 axonogenesis ARBA:ARBA00026520 KEEP_AS_NON_CORE general (21-200) 78 DANRE/notch1a GO:0007417 central nervous system development ARBA:ARBA00026561 KEEP_AS_NON_CORE very general (>200 descendants) 464 DANRE/notch1a GO:0007422 peripheral nervous system development ARBA:ARBA00084148 KEEP_AS_NON_CORE specific (1-20) 19 DANRE/notch1a GO:0009792 embryo development ending in birth or egg hatching ARBA:ARBA00029005 MARK_AS_OVER_ANNOTATED general (21-200) 122 TOO_GENERAL true but uninformative Uninformative Uninformative high-level term. DANRE/notch1a GO:0009952 anterior/posterior pattern specification ARBA:ARBA00027259 KEEP_AS_NON_CORE general (21-200) 74 DANRE/notch1a GO:0010001 glial cell differentiation ARBA:ARBA00091307 KEEP_AS_NON_CORE general (21-200) 52 DANRE/notch1a GO:0031017 exocrine pancreas development ARBA:ARBA00084589 KEEP_AS_NON_CORE leaf (0) 0 DANRE/notch1a GO:0035282 segmentation ARBA:ARBA00091150 KEEP_AS_NON_CORE general (21-200) 78 DANRE/notch1a GO:0042659 regulation of cell fate specification ARBA:ARBA00086800 KEEP_AS_NON_CORE general (21-200) 42 DANRE/notch1a GO:0045597 positive regulation of cell differentiation ARBA:ARBA00028476 MARK_AS_OVER_ANNOTATED very general (>200 descendants) 224 TOO_GENERAL true but uninformative high-level Notch1a signalling both promotes and inhibits differentiation depending on context (e.g. it restrains neurogenesis); the direction-specific high-level claim is not informative. DANRE/notch1a GO:0048568 embryonic organ development ARBA:ARBA00029173 MARK_AS_OVER_ANNOTATED general (21-200) 105 TOO_GENERAL true but uninformative Uninformative Uninformative high-level term; specific organ roles are annotated. DANRE/notch1a GO:0048646 anatomical structure formation involved in morphogenesis ARBA:ARBA00028539 MARK_AS_OVER_ANNOTATED very general (>200 descendants) 488 TOO_GENERAL true but uninformative Uninformative Uninformative high-level term. DANRE/notch1a GO:0050768 negative regulation of neurogenesis ARBA:ARBA00089677 KEEP_AS_NON_CORE general (21-200) 22 DANRE/notch1a GO:0060218 hematopoietic stem cell differentiation ARBA:ARBA00091182 KEEP_AS_NON_CORE leaf (0) 0 DANRE/notch1a GO:0060429 epithelium development ARBA:ARBA00027680 KEEP_AS_NON_CORE very general (>200 descendants) 660 DANRE/notch1a GO:0072359 circulatory system development ARBA:ARBA00027039 KEEP_AS_NON_CORE very general (>200 descendants) 399 DANRE/pax6a GO:0009952 anterior/posterior pattern specification ARBA:ARBA00027259 KEEP_AS_NON_CORE general (21-200) 74 DANRE/pax6a GO:0030154 cell differentiation ARBA:ARBA00027429 KEEP_AS_NON_CORE very general (>200 descendants) 1345 DANRE/pax6a GO:0030902 hindbrain development ARBA:ARBA00088342 KEEP_AS_NON_CORE general (21-200) 160 DANRE/pax6a GO:0045944 positive regulation of transcription by RNA polymerase II ARBA:ARBA00027996 ACCEPT specific (1-20) 12 DANRE/pax6a GO:0048593 camera-type eye morphogenesis ARBA:ARBA00091222 ACCEPT general (21-200) 36 DANRE/pax6b GO:0009952 anterior/posterior pattern specification ARBA:ARBA00027259 KEEP_AS_NON_CORE general (21-200) 74 DANRE/pax6b GO:0030154 cell differentiation ARBA:ARBA00027429 KEEP_AS_NON_CORE very general (>200 descendants) 1345 DANRE/pax6b GO:0030902 hindbrain development ARBA:ARBA00088342 KEEP_AS_NON_CORE general (21-200) 160 DANRE/pax6b GO:0045944 positive regulation of transcription by RNA polymerase II ARBA:ARBA00027996 ACCEPT specific (1-20) 12 DANRE/pax6b GO:0048593 camera-type eye morphogenesis ARBA:ARBA00091222 ACCEPT general (21-200) 36 DANRE/polb GO:0006259 DNA metabolic process ARBA:ARBA00028839 MODIFY very general (>200 descendants) 285 NEEDS_MORE_SPECIFIC true but uninformative replacement term Changed from removal for the same reason as the DNA repair row: an over-general electronic assignment is not a false one. The informative replacement is base-excision repair, the pathway in which both of this enzyme's activities operate. DANRE/prmt6 GO:0010468 regulation of gene expression ARBA:ARBA00028334 MODIFY very general (>200 descendants) 874 NEEDS_MORE_SPECIFIC true but uninformative replacement term Prmt6 regulates gene expression by depositing the transcription-repressive H3R2me2a mark and occupying the gadd45aa promoter (ChIP-qPCR, luciferase reporter; PMID:26487724). The direction and level are both known, so the generic term should be replaced by GO:0045892 negative regulation of DNA-templated transcription, which the ISS row already carries. DANRE/prmt6 GO:0070611 histone H3R2 methyltransferase activity ARBA:ARBA00084637 ACCEPT leaf (0) 0 DANRE/rbpjb GO:0000122 negative regulation of transcription by RNA polymerase II ARBA:ARBA00029133 KEEP_AS_NON_CORE specific (1-20) 10 DANRE/rbpjb GO:0005667 transcription regulator complex ARBA:ARBA00026399 ACCEPT general (21-200) 84 DANRE/rbpjb GO:0007221 positive regulation of transcription of Notch receptor target ARBA:ARBA00084930 ACCEPT leaf (0) 0 DANRE/rbpjb GO:0009653 anatomical structure morphogenesis ARBA:ARBA00026583 MARK_AS_OVER_ANNOTATED very general (>200 descendants) 1501 TOO_GENERAL true but uninformative Uninformative Uninformative high-level developmental term. DANRE/rbpjb GO:0048513 animal organ development ARBA:ARBA00029247 MARK_AS_OVER_ANNOTATED very general (>200 descendants) 1888 TOO_GENERAL true but uninformative Uninformative Uninformative high-level developmental term. DANRE/rbpjb GO:0060429 epithelium development ARBA:ARBA00027680 KEEP_AS_NON_CORE very general (>200 descendants) 660 DANRE/shha GO:0007389 pattern specification process ARBA:ARBA00027400 KEEP_AS_NON_CORE very general (>200 descendants) 307 DANRE/shha GO:0007417 central nervous system development ARBA:ARBA00026561 KEEP_AS_NON_CORE very general (>200 descendants) 464 DANRE/shha GO:0009888 tissue development ARBA:ARBA00028065 MARK_AS_OVER_ANNOTATED very general (>200 descendants) 1023 TOO_GENERAL true but uninformative general Biologically true for shha but so general that it conveys nothing beyond the many specific developmental annotations already present; flagged as over-annotation. DANRE/shha GO:0030182 neuron differentiation ARBA:ARBA00027575 KEEP_AS_NON_CORE very general (>200 descendants) 323 DANRE/shha GO:0035295 tube development ARBA:ARBA00027800 MARK_AS_OVER_ANNOTATED very general (>200 descendants) 441 TOO_GENERAL true but uninformative general Biologically true for shha but so general that it conveys nothing beyond the many specific developmental annotations already present; flagged as over-annotation. DANRE/shha GO:0042063 gliogenesis ARBA:ARBA00086246 KEEP_AS_NON_CORE general (21-200) 83 DANRE/shha GO:0042127 regulation of cell population proliferation ARBA:ARBA00027546 KEEP_AS_NON_CORE very general (>200 descendants) 258 DANRE/shha GO:0045165 cell fate commitment ARBA:ARBA00043601 KEEP_AS_NON_CORE very general (>200 descendants) 245 DANRE/shha GO:0048513 animal organ development ARBA:ARBA00029247 MARK_AS_OVER_ANNOTATED very general (>200 descendants) 1888 TOO_GENERAL true but uninformative general Biologically true for shha but so general that it conveys nothing beyond the many specific developmental annotations already present; flagged as over-annotation. DANRE/shha GO:0050793 regulation of developmental process ARBA:ARBA00028689 MARK_AS_OVER_ANNOTATED very general (>200 descendants) 1542 TOO_GENERAL true but uninformative general Biologically true for shha but so general that it conveys nothing beyond the many specific developmental annotations already present; flagged as over-annotation. DANRE/shha GO:0055002 striated muscle cell development ARBA:ARBA00084647 KEEP_AS_NON_CORE general (21-200) 25 DANRE/slc25a37 GO:0005381 iron ion transmembrane transporter activity ARBA:ARBA00045040 MODIFY specific (1-20) 6 NEEDS_MORE_SPECIFIC true but uninformative replacement term The parent is not wrong, only less specific than the evidence allows. The Rhea reaction curated for this entry names Fe(2+) explicitly and the physiological acceptor (ferrochelatase) requires ferrous iron, so the annotation is better expressed as ferrous iron transmembrane transporter activity, matching the IBA row. DANRE/smad3a GO:0000976 transcription cis-regulatory region binding ARBA:ARBA00028970 ACCEPT general (21-200) 32 DANRE/smad3a GO:0009880 embryonic pattern specification ARBA:ARBA00084933 KEEP_AS_NON_CORE general (21-200) 50 DANRE/smad3a GO:0009953 dorsal/ventral pattern formation ARBA:ARBA00027261 MARK_AS_OVER_ANNOTATED general (21-200) 28 TOO_GENERAL true but uninformative broad Dorsal/ventral patterning in the zebrafish embryo is driven mainly by BMP-SMAD1/5 signalling. No smad3a loss-of-function evidence shows a dorsal/ventral patterning defect. The organizer-gene induction reported for smad3b comes from overexpression. The ARBA rule is too broad for this R-SMAD. DANRE/smad3a GO:0030509 BMP signaling pathway ARBA:ARBA00086900 MARK_AS_OVER_ANNOTATED specific (1-20) 1 UNCLASSIFIED unclassified SMAD3 is the receptor-regulated SMAD of the TGF-beta/activin/nodal branch; its C-terminal SSVS motif is phosphorylated by TGF-beta type I receptors, and in zebrafish the Smad3 reporter is blocked by ALK4/ALK5 inhibitors. BMP signals regulate smad7 alongside Smad3 but that does not place Smad3a in the BMP pathway. No zebrafish evidence shows BMP receptors signalling through smad3a. DANRE/smad3b GO:0000976 transcription cis-regulatory region binding ARBA:ARBA00028970 ACCEPT general (21-200) 32 DANRE/smad3b GO:0009880 embryonic pattern specification ARBA:ARBA00084933 KEEP_AS_NON_CORE general (21-200) 50 DANRE/smad3b GO:0009953 dorsal/ventral pattern formation ARBA:ARBA00027261 MARK_AS_OVER_ANNOTATED general (21-200) 28 UNCLASSIFIED unclassified Dorsal/ventral patterning in zebrafish is driven mainly by BMP-SMAD1/5. Smad3b activates goosecoid when overexpressed, but no smad3b loss-of-function evidence shows a dorsal/ventral patterning defect. Treated identically on smad3a. DANRE/smad3b GO:0030509 BMP signaling pathway ARBA:ARBA00086900 MARK_AS_OVER_ANNOTATED specific (1-20) 1 INDIRECT_EFFECT overreach downstream SMAD3 is an R-SMAD of the TGF-beta/activin/nodal branch; in zebrafish the Smad3 reporter that responds to Smad3b is blocked by ALK4/ALK5 inhibitors. No evidence places smad3b downstream of BMP receptors. Treated identically on smad3a. DANRE/sult1st2 GO:0006805 xenobiotic metabolic process ARBA:ARBA00087308 ACCEPT general (21-200) 72 DANRE/tbx5a GO:0009653 anatomical structure morphogenesis ARBA:ARBA00026583 ACCEPT very general (>200 descendants) 1501 DANRE/tbx5a GO:0060429 epithelium development ARBA:ARBA00027680 MARK_AS_OVER_ANNOTATED very general (>200 descendants) 660 TOO_GENERAL true but uninformative general No zebrafish evidence that tbx5a acts in epithelium development as such. It is an ARBA machine-learning generalization from family members. DANRE/tbx5b GO:0009653 anatomical structure morphogenesis ARBA:ARBA00026583 ACCEPT very general (>200 descendants) 1501 DANRE/tbx5b GO:0060429 epithelium development ARBA:ARBA00027680 MARK_AS_OVER_ANNOTATED very general (>200 descendants) 660 TOO_GENERAL true but uninformative general No zebrafish evidence; an ARBA machine-learning generalization. Treated the same way in tbx5a. DANRE/tdp2 GO:0003677 DNA binding ARBA:ARBA00029224 KEEP_AS_NON_CORE general (21-200) 130 DANRE/tdp2 GO:0070259 tyrosyl-DNA phosphodiesterase activity ARBA:ARBA00091832 ACCEPT specific (1-20) 2 DANRE/tdp2 GO:0160108 animal gross anatomical part developmental process ARBA:ARBA00098139 MARK_AS_OVER_ANNOTATED very general (>200 descendants) 3010 INDIRECT_EFFECT overreach phenotype Broad ARBA developmental-process mapping that is uninformative for a DNA-repair phosphodiesterase and is not supported by validated in vivo phenotypes; the earlier developmental phenotypes are non-specific (PMID:39228401). Not clearly wrong at the family level, but an over-annotation for this gene product. DANRE/trpm7 GO:0004672 protein kinase activity ARBA:ARBA00027018 MODIFY general (21-200) 115 NEEDS_MORE_SPECIFIC true but uninformative replacement term TRPM7 is a channel-kinase whose C-terminal alpha-kinase domain phosphorylates serine/threonine residues (PMID:27628598 describes the protein as an ion channel fused to an alpha-kinase); the generic protein kinase term should be replaced by protein serine/threonine kinase activity (GO:0004674), which GOA already carries for this gene and which core_functions lists as the kinase activity. DANRE/trpm7 GO:0030001 metal ion transport ARBA:ARBA00028072 ACCEPT very general (>200 descendants) 347 DANRE/trpm7 GO:0008324 monoatomic cation transmembrane transporter activity ARBA:ARBA00026578 MODIFY very general (>200 descendants) 328 NEEDS_MORE_SPECIFIC true but uninformative replacement term The broad cation-transporter term is not wrong, but the activity the evidence actually supports is Mg2+ conductance. PMID:27628598 (full text) characterizes zebrafish Trpm7 as a divalent-cation channel whose permeation series includes Mg2+ and whose channel function is the primary mechanism of cellular Mg2+ homeostasis, and the same paper grounds the GO:0010960 IDA row. PMID:21183474 shows that dietary Mg2+ partially rescues the exocrine-pancreas defect of trpm7 mutants, which is the in vivo readout expected for loss of a Mg2+ entry channel. GO:0015095 (verified in QuickGO as an is_a descendant of GO:0008324) therefore replaces the parent; the calcium channel activity row remains for the Ca2+ component. This is the core molecular function listed in core_functions. DANRE/ube2ib GO:0001947 heart looping ARBA:ARBA00091286 KEEP_AS_NON_CORE leaf (0) 0 DANRE/ube2ib GO:0036306 embryonic heart tube elongation ARBA:ARBA00089896 KEEP_AS_NON_CORE leaf (0) 0 DANRE/ube2ib GO:0060216 definitive hemopoiesis ARBA:ARBA00091179 KEEP_AS_NON_CORE specific (1-20) 1 DANRE/ufsp2 GO:0071567 deUFMylase activity ARBA:ARBA00045055 ACCEPT leaf (0) 0 DANRE/vcla GO:0005911 cell-cell junction ARBA:ARBA00028427 ACCEPT general (21-200) 38 DANRE/vcla GO:0016020 membrane ARBA:ARBA00028763 ACCEPT very general (>200 descendants) 895 DANRE/vcla GO:0030016 myofibril ARBA:ARBA00028265 KEEP_AS_NON_CORE specific (1-20) 17 DANRE/vclb GO:0005911 cell-cell junction ARBA:ARBA00028427 ACCEPT general (21-200) 38 DANRE/vclb GO:0016020 membrane ARBA:ARBA00028763 ACCEPT very general (>200 descendants) 895 DANRE/vclb GO:0030016 myofibril ARBA:ARBA00028265 KEEP_AS_NON_CORE specific (1-20) 17 DEIRA/Q9RSY6 GO:0003729 mRNA binding ARBA:ARBA00028398 ACCEPT general (21-200) 74 DEIRA/Q9RSY6 GO:0005737 cytoplasm ARBA:ARBA00026971 KEEP_AS_NON_CORE very general (>200 descendants) 1146 DESRO/K9IJK6 GO:0071396 cellular response to lipid ARBA:ARBA00027803 MARK_AS_OVER_ANNOTATED general (21-200) 91 INDIRECT_EFFECT overreach indirect The focused DSPA-gamma report treats cellular response to lipid as an electronic carry-over from full-length mammalian tPA's indirect, context-specific cell biology. The salivary K9IJK6 core remains plasminogen activation; no direct DSPA-gamma evidence supports retaining this generic ARBA response process as a target function. DESRO/K9IJK6 GO:1901701 cellular response to oxygen-containing compound ARBA:ARBA00027483 MARK_AS_OVER_ANNOTATED very general (>200 descendants) 308 INDIRECT_EFFECT overreach indirect The focused DSPA-gamma report treats cellular response to oxygen-containing compound as an electronic carry-over from full-length mammalian tPA's indirect, context-specific cell biology. The salivary K9IJK6 core remains plasminogen activation; no direct DSPA-gamma evidence supports retaining this generic ARBA response process as a target function. DESRO/K9IMD0 GO:0051241 negative regulation of multicellular organismal process ARBA:ARBA00033877 ACCEPT very general (>200 descendants) 560 DESRO/K9J287 GO:0006259 DNA metabolic process ARBA:ARBA00028839 MODIFY very general (>200 descendants) 285 NEEDS_MORE_SPECIFIC true but uninformative replacement term Use the specific DNA catabolic process term already present. DESVH/Q725T9 GO:0005737 cytoplasm ARBA:ARBA00026971 ACCEPT very general (>200 descendants) 1146 DESVH/Q72F05 GO:0030001 metal ion transport ARBA:ARBA00028072 REMOVE very general (>200 descendants) 347 TERM_MISREAD wrong manual TERM_MISREAD "This annotation represents a mapping error or overly broad inference. In GO usage and biological convention, K+ is classified under ""monoatomic cation"" and ""potassium ion"" terms rather than ""metal ion"" terms. The term GO:0030001 is a sibling of GO:0006812 (monoatomic cation transport), not a parent, and is typically reserved for transition/heavy metals. Retaining this annotation would be misleading about the substrate specificity of DVU_0413." DICDI/acgA GO:0005886 plasma membrane ARBA:ARBA00027801 ACCEPT very general (>200 descendants) 415 DICDI/acgA GO:0007165 signal transduction ARBA:ARBA00029050 KEEP_AS_NON_CORE very general (>200 descendants) 937 DICDI/carA GO:0007165 signal transduction ARBA:ARBA00029050 KEEP_AS_NON_CORE very general (>200 descendants) 937 DICDI/carB GO:0007165 signal transduction ARBA:ARBA00029050 KEEP_AS_NON_CORE very general (>200 descendants) 937 DICDI/carC GO:0007165 signal transduction ARBA:ARBA00029050 KEEP_AS_NON_CORE very general (>200 descendants) 937 DICDI/carD GO:0007165 signal transduction ARBA:ARBA00029050 ACCEPT very general (>200 descendants) 937 DICDI/chlA GO:0003824 catalytic activity ARBA:ARBA00027533 MODIFY very general (>200 descendants) 6405 NEEDS_MORE_SPECIFIC true but uninformative replacement term The generic parent term should be replaced by the specific, experimentally supported molecular function of ChlA. DICDI/cotB GO:0030435 sporulation resulting in formation of a cellular spore ARBA:ARBA00028005 ACCEPT general (21-200) 32 DICDI/cotB GO:0031160 spore wall ARBA:ARBA00026804 ACCEPT specific (1-20) 13 DICDI/drkA GO:0004713 protein tyrosine kinase activity ARBA:ARBA00027631 ACCEPT general (21-200) 22 DICDI/gbpC GO:0005737 cytoplasm ARBA:ARBA00026971 ACCEPT very general (>200 descendants) 1146 DICDI/gpaB GO:0005737 cytoplasm ARBA:ARBA00026971 ACCEPT very general (>200 descendants) 1146 DICDI/gpaB GO:0007010 cytoskeleton organization ARBA:ARBA00026736 KEEP_AS_NON_CORE very general (>200 descendants) 224 DICDI/iplA GO:0005737 cytoplasm ARBA:ARBA00026971 KEEP_AS_NON_CORE very general (>200 descendants) 1146 DICDI/mhcA GO:0005737 cytoplasm ARBA:ARBA00026971 ACCEPT very general (>200 descendants) 1146 DICDI/mhcA GO:0031143 pseudopodium ARBA:ARBA00084382 KEEP_AS_NON_CORE specific (1-20) 1 DICDI/mhcA GO:0031152 aggregation involved in sorocarp development ARBA:ARBA00084367 MARK_AS_OVER_ANNOTATED leaf (0) 0 UNCLASSIFIED unclassified Genetic ablation of mhcA blocks development at a later (post-aggregation) stage; myosin-null (hmm) cells can still aggregate. The requirement is at culmination, not aggregation, so annotation to the aggregation step over-reaches. DICDI/mhcA GO:0031270 pseudopodium retraction ARBA:ARBA00086565 ACCEPT specific (1-20) 1 DICDI/mhcA GO:0048870 cell motility ARBA:ARBA00026978 KEEP_AS_NON_CORE very general (>200 descendants) 284 DICDI/phg2 GO:0009653 anatomical structure morphogenesis ARBA:ARBA00026583 REMOVE very general (>200 descendants) 1501 UNSUPPORTED overreach manual UNSUPPORTED Phg2 has no demonstrated role in morphogenesis of a multicellular structure; once development starts, phg2 mutants develop with wild-type morphology. Cell-level shape effects are already covered by cell morphogenesis. DICDI/phg2 GO:0009967 positive regulation of signal transduction ARBA:ARBA00027202 KEEP_AS_NON_CORE very general (>200 descendants) 209 DICDI/phg2 GO:0019899 enzyme binding ARBA:ARBA00026481 MARK_AS_OVER_ANNOTATED general (21-200) 77 TOO_GENERAL true but uninformative Uninformative Uninformative; specific binding partners are better captured by small GTPase binding (Rap1) and phosphatase binding (PTP3). DICDI/pkaC GO:0009653 anatomical structure morphogenesis ARBA:ARBA00026583 KEEP_AS_NON_CORE very general (>200 descendants) 1501 DICDI/pkaR GO:0010628 positive regulation of gene expression ARBA:ARBA00026655 KEEP_AS_NON_CORE general (21-200) 198 DICDI/pkaR GO:0045595 regulation of cell differentiation ARBA:ARBA00028479 KEEP_AS_NON_CORE very general (>200 descendants) 697 DICDI/pten GO:0031038 myosin II filament organization ARBA:ARBA00093689 KEEP_AS_NON_CORE specific (1-20) 2 DICDI/pten GO:0031152 aggregation involved in sorocarp development ARBA:ARBA00084367 KEEP_AS_NON_CORE leaf (0) 0 DICDI/pten GO:0046580 negative regulation of Ras protein signal transduction ARBA:ARBA00092486 KEEP_AS_NON_CORE leaf (0) 0 DICDI/pten GO:0050793 regulation of developmental process ARBA:ARBA00028689 KEEP_AS_NON_CORE very general (>200 descendants) 1542 DICDI/pten GO:0051489 regulation of filopodium assembly ARBA:ARBA00088918 KEEP_AS_NON_CORE specific (1-20) 2 DICDI/pten GO:0051898 negative regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction ARBA:ARBA00089770 ACCEPT leaf (0) 0 DICDI/pten GO:0052866 phosphatidylinositol phosphate phosphatase activity ARBA:ARBA00026416 KEEP_AS_NON_CORE specific (1-20) 20 DICDI/pten GO:0140986 G protein-coupled chemorepellent receptor signaling pathway ARBA:ARBA00087020 KEEP_AS_NON_CORE leaf (0) 0 DICDI/pten GO:1903665 negative regulation of asexual reproduction ARBA:ARBA00089236 KEEP_AS_NON_CORE specific (1-20) 10 DICDI/pyk3 GO:0003824 catalytic activity ARBA:ARBA00027533 MODIFY very general (>200 descendants) 6405 NEEDS_MORE_SPECIFIC true but uninformative replacement term Catalytic activity is far too general; the specific activity (protein tyrosine kinase activity) is experimentally established. DICDI/splB GO:0003824 catalytic activity ARBA:ARBA00027533 MODIFY very general (>200 descendants) 6405 NEEDS_MORE_SPECIFIC true but uninformative replacement term Correct but uninformative; splB is an experimentally demonstrated protein tyrosine kinase, so the specific term should be used. DICDI/statA GO:0042802 identical protein binding ARBA:ARBA00027930 ACCEPT specific (1-20) 1 DICDI/statA GO:0045892 negative regulation of DNA-templated transcription ARBA:ARBA00029084 ACCEPT general (21-200) 39 DICDI/statC GO:0042802 identical protein binding ARBA:ARBA00027930 KEEP_AS_NON_CORE specific (1-20) 1 DICDI/statC GO:0045892 negative regulation of DNA-templated transcription ARBA:ARBA00029084 ACCEPT general (21-200) 39 DICDI/stlB GO:0044550 secondary metabolite biosynthetic process ARBA:ARBA00029064 ACCEPT general (21-200) 164 DICDI/tagC GO:0005886 plasma membrane ARBA:ARBA00027801 ACCEPT very general (>200 descendants) 415 DICDI/tagC GO:0030154 cell differentiation ARBA:ARBA00027429 KEEP_AS_NON_CORE very general (>200 descendants) 1345 DORPE/AP180 GO:0006898 receptor-mediated endocytosis ARBA:ARBA00044584 MARK_AS_OVER_ANNOTATED general (21-200) 30 TOO_GENERAL true but uninformative already annotated The characterized function of squid AP180 is in synaptic vesicle endocytosis, not receptor-mediated endocytosis. While the clathrin machinery is shared, receptor-mediated endocytosis implies cargo selection via receptor internalization signals, which is not what squid AP180 has been shown to do. The more accurate term GO:0048488 (synaptic vesicle endocytosis) is already annotated with IMP evidence. DORPE/AP180 GO:0012505 endomembrane system ARBA:ARBA00028953 ACCEPT very general (>200 descendants) 357 DORPE/AP180 GO:0016020 membrane ARBA:ARBA00028763 ACCEPT very general (>200 descendants) 895 DORPE/AP180 GO:0040011 locomotion ARBA:ARBA00026452 REMOVE general (21-200) 95 WRONG_PROCESS wrong manual WRONG_PROCESS This annotation is inappropriate for a clathrin assembly protein. AP180 functions in clathrin coat assembly and synaptic vesicle endocytosis. Any connection to locomotion would be extremely indirect (via synaptic transmission). This appears to be a spurious ARBA prediction and does not represent a meaningful function of the protein. DORPE/AP180 GO:0048488 synaptic vesicle endocytosis ARBA:ARBA00091614 ACCEPT specific (1-20) 5 DORPE/P21613 GO:0003774 cytoskeletal motor activity ARBA:ARBA00028547 ACCEPT specific (1-20) 10 DORPE/P21613 GO:0005737 cytoplasm ARBA:ARBA00026971 ACCEPT very general (>200 descendants) 1146 DORPE/P21613 GO:0007097 nuclear migration ARBA:ARBA00026920 MARK_AS_OVER_ANNOTATED specific (1-20) 18 UNCLASSIFIED unclassified While kinesin-1 does participate in nuclear migration in some organisms, this function has not been demonstrated for the squid kinesin heavy chain. The available literature on squid kinesin focuses on axonal transport, not nuclear positioning. This appears to be an over-extension from other kinesin-1 family members. DORPE/P21613 GO:0007292 female gamete generation ARBA:ARBA00028339 MARK_AS_OVER_ANNOTATED general (21-200) 99 NO_EVIDENCE overreach no published evidence There is no published evidence linking squid kinesin heavy chain P21613 to female gamete generation. The annotation likely derives from ARBA rules built on kinesin-1 function in Drosophila oogenesis. While plausible, it is an unsupported extrapolation for this particular protein. DORPE/P21613 GO:0015630 microtubule cytoskeleton ARBA:ARBA00029268 ACCEPT general (21-200) 108 DORPE/P21613 GO:0030951 establishment or maintenance of microtubule cytoskeleton polarity ARBA:ARBA00087868 MARK_AS_OVER_ANNOTATED specific (1-20) 2 NO_EVIDENCE overreach no evidence This annotation confuses kinesin's dependence on microtubule polarity for directional transport with a role in establishing or maintaining that polarity. Kinesin-1 reads microtubule polarity but does not set it. There is no evidence that squid kinesin heavy chain is involved in establishing or maintaining microtubule polarity. DORPE/P21613 GO:0032991 protein-containing complex ARBA:ARBA00028902 MODIFY very general (>200 descendants) 2083 NEEDS_MORE_SPECIFIC true but uninformative replacement term "The UniProt entry states kinesin is an ""oligomer composed of two heavy chains and two light chains,"" which is the kinesin-1 holoenzyme. The generic protein-containing complex term should be replaced with the specific kinesin I complex term." DORPE/P21613 GO:0043005 neuron projection ARBA:ARBA00027418 KEEP_AS_NON_CORE general (21-200) 135 DORPE/P21613 GO:0048489 synaptic vesicle transport ARBA:ARBA00091615 ACCEPT specific (1-20) 9 DORPE/P21613 GO:0098957 anterograde axonal transport of mitochondrion ARBA:ARBA00090823 MODIFY leaf (0) 0 TOO_SPECIFIC overreach replacement term While kinesin-1-dependent anterograde mitochondrial transport is well established in mammals, the specific cargo (mitochondria) has not been demonstrated for squid kinesin. The squid giant axon studies focus on general organelle and vesicle transport. The broader term anterograde axonal transport better reflects the directly supported biology. DORPE/P21613 GO:0120544 polypeptide conformation or assembly isomerase activity ARBA:ARBA00090782 REMOVE specific (1-20) 9 WRONG_ACTIVITY wrong manual WRONG_ACTIVITY Kinesin-1 is a microtubule motor protein. It does not have any known chaperone, foldase, or isomerase activity. This annotation is likely a false positive from the ARBA automated annotation pipeline and should be removed. No literature supports this function for any kinesin-1 family member. DORPE/TDO GO:0006569 L-tryptophan catabolic process ARBA:ARBA00026552 ACCEPT specific (1-20) 1 DROME/18w GO:0009653 anatomical structure morphogenesis ARBA:ARBA00026583 ACCEPT very general (>200 descendants) 1501 DROME/18w GO:0048666 neuron development ARBA:ARBA00028378 KEEP_AS_NON_CORE general (21-200) 186 DROME/AGO3 GO:0016891 RNA endonuclease activity producing 5'-phosphomonoesters, hydrolytic mechanism ARBA:ARBA00028553 ACCEPT specific (1-20) 15 DROME/AGO3 GO:0034584 piRNA binding ARBA:ARBA00092433 ACCEPT leaf (0) 0 DROME/AGO3 GO:0043186 P granule ARBA:ARBA00026989 ACCEPT specific (1-20) 2 DROME/AGO3 GO:0140965 secondary piRNA processing ARBA:ARBA00087010 ACCEPT leaf (0) 0 DROME/AGO3 GO:0141009 transposable element silencing by piRNA-mediated mRNA destabilization ARBA:ARBA00092222 ACCEPT leaf (0) 0 DROME/AMPKalpha GO:0004679 AMP-activated protein kinase activity ARBA:ARBA00027028 ACCEPT leaf (0) 0 DROME/AMPKalpha GO:0005737 cytoplasm ARBA:ARBA00026971 ACCEPT very general (>200 descendants) 1146 DROME/AMPKalpha GO:0043050 nematode pharyngeal pumping ARBA:ARBA00084835 REMOVE leaf (0) 0 WRONG_TAXON wrong manual WRONG_TAXON Nematode-specific process with no counterpart in Drosophila; taxonomically inappropriate electronic annotation. DROME/Acaa GO:0003988 acetyl-CoA C-acyltransferase activity ARBA:ARBA00043303 ACCEPT specific (1-20) 2 DROME/Acaa GO:0006629 lipid metabolic process ARBA:ARBA00028591 MARK_AS_OVER_ANNOTATED very general (>200 descendants) 608 TOO_GENERAL true but uninformative already annotated Non-informative ancestor of GO:0006635 (fatty acid beta-oxidation), which is the specific process already annotated. DROME/Acadvl GO:0006631 fatty acid metabolic process ARBA:ARBA00028669 KEEP_AS_NON_CORE general (21-200) 94 DROME/Akt1 GO:0008286 insulin receptor signaling pathway ARBA:ARBA00092359 ACCEPT specific (1-20) 1 DROME/Akt1 GO:0008582 regulation of synaptic assembly at neuromuscular junction ARBA:ARBA00085089 UNDECIDED specific (1-20) 3 DROME/Ass GO:0008652 amino acid biosynthetic process ARBA:ARBA00027355 ACCEPT general (21-200) 52 DROME/CCDC53 GO:0005737 cytoplasm ARBA:ARBA00026971 MODIFY very general (>200 descendants) 1146 NEEDS_MORE_SPECIFIC true but uninformative replacement term Correct but less specific than the evidence supports; early endosome (GO:0005769) is already annotated to this gene. DROME/CG10814 GO:0016706 2-oxoglutarate-dependent dioxygenase activity ARBA:ARBA00027633 MODIFY general (21-200) 65 NEEDS_MORE_SPECIFIC true but uninformative replacement term Correct at the family level (Fe(II)/2-oxoglutarate-dependent dioxygenase) but more general than the evidence supports. The specific reaction, gamma-butyrobetaine dioxygenase activity (GO:0008336), is already annotated to this gene and is the appropriate replacement. DROME/CG3515 GO:0016070 RNA metabolic process ARBA:ARBA00028985 UNDECIDED very general (>200 descendants) 507 DROME/CG42331 GO:0003006 developmental process involved in reproduction ARBA:ARBA00026397 PENDING very general (>200 descendants) 482 DROME/CG42331 GO:0022412 cellular process involved in reproduction in multicellular organism ARBA:ARBA00028215 PENDING general (21-200) 136 DROME/CG42331 GO:0048646 anatomical structure formation involved in morphogenesis ARBA:ARBA00028539 PENDING very general (>200 descendants) 488 DROME/CG43742 GO:0051604 protein maturation ARBA:ARBA00026902 UNDECIDED general (21-200) 74 DROME/CG4610 GO:0005737 cytoplasm ARBA:ARBA00026971 KEEP_AS_NON_CORE very general (>200 descendants) 1146 DROME/CG4610 GO:0070899 mitochondrial tRNA wobble uridine modification ARBA:ARBA00086587 ACCEPT specific (1-20) 1 DROME/CG6051 GO:0004438 phosphatidylinositol-3-phosphate phosphatase activity ARBA:ARBA00035068 REMOVE leaf (0) 0 ROLE_CONFUSION wrong manual ROLE_CONFUSION This annotation is fundamentally incorrect. CG6051 contains a FYVE domain that BINDS phosphatidylinositol-3-phosphate (PI3P) but does not possess phosphatase activity. The protein lacks any phosphatase catalytic domains. The human ortholog ZFYVE28/LST2 is well-characterized as an adaptor/scaffold protein that is phosphorylated BY kinases (mTORC1), not as a phosphatase itself. This appears to be an erroneous automated prediction conflating PI3P binding with PI3P phosphatase activity. DROME/CG6051 GO:0004721 phosphoprotein phosphatase activity ARBA:ARBA00027651 REMOVE general (21-200) 36 ROLE_CONFUSION wrong manual ROLE_CONFUSION This annotation is incorrect. CG6051/LST2 does not have phosphatase activity. Instead, it is a SUBSTRATE of phosphorylation - the protein is phosphorylated by mTORC1 kinase at multiple serine residues (S549, S550, S810 in Drosophila). The protein lacks any phosphatase catalytic domains. This is another erroneous automated prediction that misinterprets the protein as having enzymatic activity when it is actually an adaptor/regulatory protein. DROME/CG6051 GO:0005829 cytosol ARBA:ARBA00029243 KEEP_AS_NON_CORE general (21-200) 73 DROME/CG6051 GO:0016020 membrane ARBA:ARBA00028763 MODIFY very general (>200 descendants) 895 NEEDS_MORE_SPECIFIC true but uninformative replacement term "This annotation is too vague. CG6051 does associate with membranes, but specifically with early endosomal membranes through PI3P binding via its FYVE domain. The generic ""membrane"" term provides little functional information. The more specific ""early endosome membrane"" (GO:0031901) annotation already exists and better captures the protein localization." DROME/CG6051 GO:0019899 enzyme binding ARBA:ARBA00026481 MARK_AS_OVER_ANNOTATED general (21-200) 77 TOO_GENERAL true but uninformative general "This annotation is likely correct but too general to be useful. The human ortholog LST2 is known to be phosphorylated by mTORC1 kinase, suggesting it binds this enzyme. It may also interact with EGFR or other signaling proteins. However, ""enzyme binding"" is so broad it provides minimal functional insight. Without specific experimental evidence in Drosophila for which enzymes are bound, this annotation adds little value. More specific terms like ""protein kinase binding"" (GO:0019901) would be more appropriate if supported by evidence." DROME/CG6051 GO:0046474 glycerophospholipid biosynthetic process ARBA:ARBA00028351 REMOVE general (21-200) 23 WRONG_PROCESS wrong manual WRONG_PROCESS This annotation is incorrect. CG6051/LST2 does not participate in glycerophospholipid biosynthesis. The protein binds to phosphatidylinositol-3-phosphate (a phospholipid) via its FYVE domain but has no biosynthetic activity. There are no lipid biosynthesis domains in the protein. This appears to be an erroneous automated prediction that confused lipid binding with lipid biosynthesis. The protein functions in signaling and endosomal trafficking, not in lipid metabolism. DROME/CG6051 GO:0046856 phosphatidylinositol dephosphorylation ARBA:ARBA00028324 REMOVE leaf (0) 0 ROLE_CONFUSION wrong manual ROLE_CONFUSION This annotation is incorrect. CG6051/LST2 does not catalyze phosphatidylinositol dephosphorylation. The protein binds PI3P through its FYVE domain but has no phosphatase activity. This is another instance of automated prediction incorrectly inferring enzymatic activity from lipid-binding capability. The protein is an adaptor/scaffold in signaling pathways, not a metabolic enzyme. All phosphatase-related annotations for this protein are erroneous. DROME/CG6051 GO:0052629 phosphatidylinositol-3,5-bisphosphate 3-phosphatase activity ARBA:ARBA00047230 REMOVE leaf (0) 0 ROLE_CONFUSION wrong manual ROLE_CONFUSION This annotation is completely incorrect. CG6051/LST2 has no phosphatase activity whatsoever. The protein contains only a FYVE zinc finger domain for PI3P binding and lacks any phosphatase catalytic domains. This specific phosphatase activity annotation is particularly problematic as it suggests a very specific enzymatic function that the protein absolutely does not possess. The human ortholog is well-characterized as a signaling adaptor, not an enzyme. This is a clear case of over-annotation by automated systems. DROME/CG6051 GO:0060090 molecular adaptor activity ARBA:ARBA00026447 ACCEPT general (21-200) 176 DROME/CG6051 GO:0061952 midbody abscission ARBA:ARBA00029210 REMOVE leaf (0) 0 UNSUPPORTED overreach manual UNSUPPORTED This annotation lacks supporting evidence. While some FYVE domain proteins participate in cytokinesis and midbody abscission through endosomal trafficking roles, there is no specific evidence that CG6051/LST2 is involved in this process. The protein was tested in fertility screens but showed no significant phenotype. The human ortholog is characterized for its role in growth factor signaling, not cytokinesis. This appears to be an over-reaching automated prediction based on weak domain similarity to other FYVE proteins that do have cytokinesis roles. Without experimental support, this annotation should be removed. DROME/CG6836 GO:0016020 membrane ARBA:ARBA00028763 ACCEPT very general (>200 descendants) 895 DROME/CG8142 GO:0000076 DNA replication checkpoint signaling ARBA:ARBA00090203 KEEP_AS_NON_CORE specific (1-20) 2 DROME/CG8142 GO:0006271 DNA strand elongation involved in DNA replication ARBA:ARBA00028969 ACCEPT specific (1-20) 10 DROME/CG8142 GO:0006281 DNA repair ARBA:ARBA00029008 KEEP_AS_NON_CORE general (21-200) 74 DROME/CG8142 GO:0031391 Elg1 RFC-like complex ARBA:ARBA00028328 ACCEPT leaf (0) 0 DROME/CG8353 GO:0005737 cytoplasm ARBA:ARBA00026971 KEEP_AS_NON_CORE very general (>200 descendants) 1146 DROME/CG8353 GO:0042802 identical protein binding ARBA:ARBA00027930 UNDECIDED specific (1-20) 1 DROME/CG8353 GO:0055086 nucleobase-containing small molecule metabolic process ARBA:ARBA00027681 KEEP_AS_NON_CORE very general (>200 descendants) 576 DROME/CG8353 GO:0072527 pyrimidine-containing compound metabolic process ARBA:ARBA00026859 KEEP_AS_NON_CORE general (21-200) 139 DROME/CG8353 GO:1901135 carbohydrate derivative metabolic process ARBA:ARBA00026297 KEEP_AS_NON_CORE very general (>200 descendants) 637 DROME/CRY GO:0009416 response to light stimulus ARBA:ARBA00028128 ACCEPT general (21-200) 101 DROME/Caf1-55 GO:0042826 histone deacetylase binding ARBA:ARBA00088244 ACCEPT leaf (0) 0 DROME/Cdk12 GO:0016301 kinase activity ARBA:ARBA00026285 ACCEPT very general (>200 descendants) 347 DROME/Ctns GO:0015179 L-amino acid transmembrane transporter activity ARBA:ARBA00028768 MODIFY general (21-200) 56 NEEDS_MORE_SPECIFIC true but uninformative replacement term Endogenous lysosomal localization, cystine accumulation in dCTNS mutants and transport-dependent starvation rescue identify cystine as the physiologically relevant substrate. The broad annotation is sound but does not express this experimentally established specificity. DROME/Ctns GO:1904919 L-cystine transmembrane transport from lysosomal lumen to cytosol ARBA:ARBA00098245 ACCEPT leaf (0) 0 DROME/CycA GO:0000278 mitotic cell cycle ARBA:ARBA00028458 ACCEPT general (21-200) 121 DROME/CycA GO:0005634 nucleus ARBA:ARBA00026330 ACCEPT very general (>200 descendants) 473 DROME/CycA GO:0051301 cell division ARBA:ARBA00027793 ACCEPT general (21-200) 120 DROME/Dark GO:0005829 cytosol ARBA:ARBA00029243 ACCEPT general (21-200) 73 DROME/Dark GO:0006915 apoptotic process ARBA:ARBA00027755 MODIFY general (21-200) 115 NEEDS_MORE_SPECIFIC true but uninformative replacement term Dark is not a generic executor of all apoptosis; it is the Dronc-recruiting scaffold for the upstream apoptotic signaling platform. Replace the top-level term with positive regulation of apoptotic signaling pathway. DROME/Dark GO:0160108 animal gross anatomical part developmental process ARBA:ARBA00098139 MARK_AS_OVER_ANNOTATED very general (>200 descendants) 3010 TOO_GENERAL true but uninformative uninformative Dark is directly reused in several developmental contexts through apoptosome-mediated Dronc activation, but animal gross anatomical part developmental process is an uninformative parent and should not be the propagated label for the protein. DROME/Dcp-1 GO:0016322 neuron remodeling ARBA:ARBA00086716 UNDECIDED leaf (0) 0 DROME/Dcp-1 GO:0045476 nurse cell apoptotic process ARBA:ARBA00043473 KEEP_AS_NON_CORE leaf (0) 0 DROME/Dcp-1 GO:0045751 negative regulation of Toll signaling pathway ARBA:ARBA00084359 KEEP_AS_NON_CORE leaf (0) 0 DROME/Dcp-1 GO:0097194 execution phase of apoptosis ARBA:ARBA00090101 ACCEPT specific (1-20) 6 DROME/Dcp-1 GO:1990525 BIR domain binding ARBA:ARBA00090447 UNDECIDED leaf (0) 0 DROME/Diap1 GO:0005829 cytosol ARBA:ARBA00029243 ACCEPT general (21-200) 73 DROME/Diap1 GO:0016755 aminoacyltransferase activity ARBA:ARBA00026304 MODIFY general (21-200) 62 NEEDS_MORE_SPECIFIC true but uninformative replacement term GO:0016755 is an uninformative aminoacyltransferase parent for a RING ubiquitin ligase; GO:0061630 captures the actual chemistry. DROME/Diap1 GO:0022416 chaeta development ARBA:ARBA00092651 KEEP_AS_NON_CORE specific (1-20) 4 DROME/Diap1 GO:0031625 ubiquitin protein ligase binding ARBA:ARBA00028807 UNDECIDED leaf (0) 0 DROME/Diap1 GO:0043027 cysteine-type endopeptidase inhibitor activity involved in apoptotic process ARBA:ARBA00084669 ACCEPT leaf (0) 0 DROME/Diap1 GO:0048471 perinuclear region of cytoplasm ARBA:ARBA00091589 UNDECIDED specific (1-20) 7 DROME/Diap1 GO:0070936 protein K48-linked ubiquitination ARBA:ARBA00086253 KEEP_AS_NON_CORE leaf (0) 0 DROME/Diap1 GO:0089720 caspase binding ARBA:ARBA00087760 ACCEPT leaf (0) 0 DROME/Diap1 GO:0140096 catalytic activity, acting on a protein ARBA:ARBA00027983 MODIFY very general (>200 descendants) 629 NEEDS_MORE_SPECIFIC true but uninformative replacement term DIAP1 is not just any protein-directed catalyst; the ARBA transfer should point to the specific RING E3 ubiquitin ligase activity. DROME/Diap2 GO:0005829 cytosol ARBA:ARBA00029243 UNDECIDED general (21-200) 73 DROME/Diap2 GO:0016755 aminoacyltransferase activity ARBA:ARBA00026304 MODIFY general (21-200) 62 NEEDS_MORE_SPECIFIC true but uninformative replacement term DIAP2 is a RING-dependent ubiquitin protein ligase; GO:0061630 is the specific catalytic activity rather than the high-level transferase parent imported by ARBA. DROME/Diap2 GO:0022416 chaeta development ARBA:ARBA00092651 MARK_AS_OVER_ANNOTATED specific (1-20) 4 INDIRECT_EFFECT overreach phenotype The available Diap2-specific evidence is an ectopic caspase-blockade phenotype in the scutellum; as with the FlyBase IMP row, that overexpression result does not establish chaeta development as an endogenous DIAP2 function. DROME/Diap2 GO:0031625 ubiquitin protein ligase binding ARBA:ARBA00028807 UNDECIDED leaf (0) 0 DROME/Diap2 GO:0043027 cysteine-type endopeptidase inhibitor activity involved in apoptotic process ARBA:ARBA00084669 ACCEPT leaf (0) 0 DROME/Diap2 GO:0048471 perinuclear region of cytoplasm ARBA:ARBA00091589 KEEP_AS_NON_CORE specific (1-20) 7 DROME/Diap2 GO:0070936 protein K48-linked ubiquitination ARBA:ARBA00086253 UNDECIDED leaf (0) 0 DROME/Diap2 GO:0089720 caspase binding ARBA:ARBA00087760 ACCEPT leaf (0) 0 DROME/Diap2 GO:0140096 catalytic activity, acting on a protein ARBA:ARBA00027983 MODIFY very general (>200 descendants) 629 NEEDS_MORE_SPECIFIC true but uninformative replacement term DIAP2 does not merely have unspecified catalytic activity on a protein; it is a RING E3 that catalyzes ubiquitin transfer to IMD, DREDD, Kenny, and DrICE. DROME/Dif GO:0000977 RNA polymerase II transcription regulatory region sequence-specific DNA binding ARBA:ARBA00028973 ACCEPT specific (1-20) 15 DROME/Dif GO:0001228 DNA-binding transcription activator activity, RNA polymerase II-specific ARBA:ARBA00027759 ACCEPT leaf (0) 0 DROME/Dif GO:0002225 positive regulation of antimicrobial peptide production ARBA:ARBA00087827 ACCEPT specific (1-20) 10 DROME/Dif GO:0005654 nucleoplasm ARBA:ARBA00026290 ACCEPT general (21-200) 65 DROME/Dif GO:0007249 canonical NF-kappaB signal transduction ARBA:ARBA00085080 KEEP_AS_NON_CORE specific (1-20) 2 DROME/Dif GO:0008063 Toll signaling pathway ARBA:ARBA00093120 ACCEPT leaf (0) 0 DROME/Dif GO:0035206 regulation of hemocyte proliferation ARBA:ARBA00091713 KEEP_AS_NON_CORE specific (1-20) 2 DROME/Dif GO:0045087 innate immune response ARBA:ARBA00027946 ACCEPT general (21-200) 39 DROME/Dif GO:0048935 peripheral nervous system neuron development ARBA:ARBA00092968 KEEP_AS_NON_CORE specific (1-20) 2 DROME/Dl GO:0000902 cell morphogenesis ARBA:ARBA00028811 KEEP_AS_NON_CORE general (21-200) 157 DROME/Dl GO:0007498 mesoderm development ARBA:ARBA00084318 KEEP_AS_NON_CORE general (21-200) 51 DROME/Dl GO:0008587 imaginal disc-derived wing margin morphogenesis ARBA:ARBA00085082 KEEP_AS_NON_CORE specific (1-20) 1 DROME/Dl GO:0009986 cell surface ARBA:ARBA00027349 ACCEPT specific (1-20) 14 DROME/Dl GO:0016330 second mitotic wave involved in compound eye morphogenesis ARBA:ARBA00086657 KEEP_AS_NON_CORE leaf (0) 0 DROME/Dl GO:0030718 germ-line stem cell population maintenance ARBA:ARBA00088373 KEEP_AS_NON_CORE specific (1-20) 2 DROME/Dl GO:0035214 eye-antennal disc development ARBA:ARBA00091693 KEEP_AS_NON_CORE specific (1-20) 10 DROME/Dl GO:0036011 imaginal disc-derived leg segmentation ARBA:ARBA00090233 KEEP_AS_NON_CORE specific (1-20) 1 DROME/Dl GO:0042063 gliogenesis ARBA:ARBA00086246 KEEP_AS_NON_CORE general (21-200) 83 DROME/Dl GO:0043208 glycosphingolipid binding ARBA:ARBA00086545 KEEP_AS_NON_CORE specific (1-20) 6 DROME/Dl GO:0045179 apical cortex ARBA:ARBA00092806 KEEP_AS_NON_CORE specific (1-20) 2 DROME/Dl GO:0046331 lateral inhibition ARBA:ARBA00093161 ACCEPT leaf (0) 0 DROME/Dl GO:0048018 receptor ligand activity ARBA:ARBA00028558 ACCEPT general (21-200) 34 DROME/Dl GO:0048100 wing disc anterior/posterior pattern formation ARBA:ARBA00089998 KEEP_AS_NON_CORE leaf (0) 0 DROME/Dl GO:0048646 anatomical structure formation involved in morphogenesis ARBA:ARBA00028539 KEEP_AS_NON_CORE very general (>200 descendants) 488 DROME/Dl GO:0048666 neuron development ARBA:ARBA00028378 KEEP_AS_NON_CORE general (21-200) 186 DROME/Dl GO:0048863 stem cell differentiation ARBA:ARBA00090702 KEEP_AS_NON_CORE general (21-200) 37 DROME/Dl GO:0050793 regulation of developmental process ARBA:ARBA00028689 KEEP_AS_NON_CORE very general (>200 descendants) 1542 DROME/Dl GO:0060429 epithelium development ARBA:ARBA00027680 KEEP_AS_NON_CORE very general (>200 descendants) 660 DROME/Doc1 GO:0006357 regulation of transcription by RNA polymerase II ARBA:ARBA00028137 ACCEPT general (21-200) 56 DROME/Doc1 GO:0160108 animal gross anatomical part developmental process ARBA:ARBA00098139 MARK_AS_OVER_ANNOTATED very general (>200 descendants) 3010 TOO_GENERAL true but uninformative uninformative Not wrong but uninformative: more specific developmental processes (heart, amnioserosa, wing disc primordium, Malpighian tubule) are already annotated with experimental evidence. DROME/DrICE GO:0016322 neuron remodeling ARBA:ARBA00086716 UNDECIDED leaf (0) 0 DROME/DrICE GO:0045476 nurse cell apoptotic process ARBA:ARBA00043473 KEEP_AS_NON_CORE leaf (0) 0 DROME/DrICE GO:0045751 negative regulation of Toll signaling pathway ARBA:ARBA00084359 KEEP_AS_NON_CORE leaf (0) 0 DROME/DrICE GO:0097194 execution phase of apoptosis ARBA:ARBA00090101 ACCEPT specific (1-20) 6 DROME/DrICE GO:1990525 BIR domain binding ARBA:ARBA00090447 KEEP_AS_NON_CORE leaf (0) 0 DROME/Dscam1 GO:0042802 identical protein binding ARBA:ARBA00027930 ACCEPT specific (1-20) 1 DROME/Dscam1 GO:0048812 neuron projection morphogenesis ARBA:ARBA00026689 ACCEPT general (21-200) 94 DROME/Dsor1 GO:0005737 cytoplasm ARBA:ARBA00026971 ACCEPT very general (>200 descendants) 1146 DROME/Ech1 GO:0005737 cytoplasm ARBA:ARBA00026971 MARK_AS_OVER_ANNOTATED very general (>200 descendants) 1146 TOO_GENERAL true but uninformative Uninformative Uninformative over-general term superseded by the specific mitochondrion/peroxisome localization annotations. DROME/Egfr GO:0009966 regulation of signal transduction ARBA:ARBA00027204 MODIFY very general (>200 descendants) 696 OTHER_TERM different term needed replacement term The ARBA signal-transduction parent is too general to retain on a well-characterized receptor. Egfr directly executes epidermal growth factor receptor signaling, which is already represented by GO:0007173. DROME/Egfr GO:0038127 ERBB signaling pathway ARBA:ARBA00034175 MODIFY specific (1-20) 11 NEEDS_MORE_SPECIFIC true but uninformative replacement term The ARBA ERBB signaling call captures the same EGF-receptor-family biology but uses a vertebrate ERBB family term. Drosophila Egfr should be represented with GO:0007173 epidermal growth factor receptor signaling pathway. DROME/Egfr GO:0042127 regulation of cell population proliferation ARBA:ARBA00027546 KEEP_AS_NON_CORE very general (>200 descendants) 258 DROME/Egm GO:0006631 fatty acid metabolic process ARBA:ARBA00028669 KEEP_AS_NON_CORE general (21-200) 94 DROME/Elba1 GO:0003682 chromatin binding ARBA:ARBA00027831 ACCEPT specific (1-20) 10 DROME/Elba1 GO:0010468 regulation of gene expression ARBA:ARBA00028334 ACCEPT very general (>200 descendants) 874 DROME/Elba1 GO:0043565 sequence-specific DNA binding ARBA:ARBA00026779 ACCEPT general (21-200) 60 DROME/Elba2 GO:0003682 chromatin binding ARBA:ARBA00027831 ACCEPT specific (1-20) 10 DROME/Elba2 GO:0010468 regulation of gene expression ARBA:ARBA00028334 ACCEPT very general (>200 descendants) 874 DROME/Elba2 GO:0043565 sequence-specific DNA binding ARBA:ARBA00026779 ACCEPT general (21-200) 60 DROME/Hsp22 GO:0009408 response to heat ARBA:ARBA00028092 ACCEPT specific (1-20) 7 DROME/Hsp23 GO:0005737 cytoplasm ARBA:ARBA00026971 ACCEPT very general (>200 descendants) 1146 DROME/Hsp23 GO:0009408 response to heat ARBA:ARBA00028092 ACCEPT specific (1-20) 7 DROME/Hsp23 GO:0042026 protein refolding ARBA:ARBA00043587 ACCEPT leaf (0) 0 DROME/Hsp23 GO:0051082 unfolded protein binding ARBA:ARBA00027557 MODIFY leaf (0) 0 OTHER_TERM different term needed replacement term Live QuickGO confirms that GO:0051082 is obsolete and GO:0140309 is active, named unfolded protein holdase activity. Its definition allows delivery to an acceptor molecule OR a specific location; it does not require transport between compartments. Full PMID:16572729 directly demonstrates client holding and later recovery by the reticulocyte chaperone machinery, with different efficiencies for each small Hsp. The active holdase term captures that activity; replacing the obsolete term with itself or awaiting a new term is unnecessary. DROME/Hsp26 GO:0005737 cytoplasm ARBA:ARBA00026971 ACCEPT very general (>200 descendants) 1146 DROME/Hsp26 GO:0009408 response to heat ARBA:ARBA00028092 ACCEPT specific (1-20) 7 DROME/Hsp26 GO:0042026 protein refolding ARBA:ARBA00043587 ACCEPT leaf (0) 0 DROME/Hsp26 GO:0051082 unfolded protein binding ARBA:ARBA00027557 MODIFY leaf (0) 0 TOO_GENERAL true but uninformative general GO:0051082 is obsolete. Hsp26-mediated ATP-independent client holding is an in-situ small-HSP activity, not carrier-holdase activity, so the row should point to the proposed general holdase chaperone activity term rather than GO:0140309. DROME/Hsp27 GO:0005737 cytoplasm ARBA:ARBA00026971 ACCEPT very general (>200 descendants) 1146 DROME/Hsp27 GO:0009408 response to heat ARBA:ARBA00028092 ACCEPT specific (1-20) 7 DROME/Hsp27 GO:0042026 protein refolding ARBA:ARBA00043587 KEEP_AS_NON_CORE leaf (0) 0 DROME/Hsp27 GO:0051082 unfolded protein binding ARBA:ARBA00027557 MODIFY leaf (0) 0 UNCLASSIFIED unclassified Holdase binding of unfolded clients is well supported for Hsp27, but GO:0051082 is obsolete and GO:0140309 keeps a carrier-specific definition (go-ontology#30552). Replace with the proposed holdase chaperone activity NTR (see proposed_new_terms), as for the IBA row above. DROME/Hsp83 GO:0101031 protein folding chaperone complex ARBA:ARBA00026483 ACCEPT specific (1-20) 7 DROME/HtrA2 GO:0005739 mitochondrion ARBA:ARBA00026962 ACCEPT general (21-200) 70 DROME/HtrA2 GO:0007005 mitochondrion organization ARBA:ARBA00026723 KEEP_AS_NON_CORE general (21-200) 37 DROME/HtrA2 GO:0008233 peptidase activity ARBA:ARBA00027408 KEEP_AS_NON_CORE general (21-200) 81 DROME/HtrA2 GO:0012501 programmed cell death ARBA:ARBA00028943 ACCEPT general (21-200) 147 DROME/HtrA2 GO:0016020 membrane ARBA:ARBA00028763 KEEP_AS_NON_CORE very general (>200 descendants) 895 DROME/HtrA2 GO:0043065 positive regulation of apoptotic process ARBA:ARBA00027745 ACCEPT general (21-200) 68 DROME/Hus1-like GO:0006259 DNA metabolic process ARBA:ARBA00028839 KEEP_AS_NON_CORE very general (>200 descendants) 285 DROME/IKKepsilon GO:0009967 positive regulation of signal transduction ARBA:ARBA00027202 KEEP_AS_NON_CORE very general (>200 descendants) 209 DROME/IKKepsilon GO:0010628 positive regulation of gene expression ARBA:ARBA00026655 KEEP_AS_NON_CORE general (21-200) 198 DROME/IKKepsilon GO:0045089 positive regulation of innate immune response ARBA:ARBA00034392 ACCEPT general (21-200) 103 DROME/Ing5 GO:0032991 protein-containing complex ARBA:ARBA00028902 MODIFY very general (>200 descendants) 2083 NEEDS_MORE_SPECIFIC true but uninformative replacement term Correct but uninformative; replace with GO:0070776 MOZ/MORF histone acetyltransferase complex, already annotated. DROME/Kpc1 GO:0016567 protein ubiquitination ARBA:ARBA00027966 ACCEPT specific (1-20) 14 DROME/Kpc1 GO:0030163 protein catabolic process ARBA:ARBA00027403 KEEP_AS_NON_CORE general (21-200) 66 DROME/Lis-1 GO:0030286 dynein complex ARBA:ARBA00085634 MODIFY specific (1-20) 4 TOO_SPECIFIC overreach replacement term LIS1 is a transiently associated regulator rather than a dynein subunit; microtubule associated complex (the parent, and the term used for the human ortholog) plus dynein complex binding better represent this. DROME/Lis-1 GO:0051225 spindle assembly ARBA:ARBA00089339 ACCEPT specific (1-20) 18 DROME/Lis-1 GO:0051299 centrosome separation ARBA:ARBA00089326 ACCEPT specific (1-20) 1 DROME/Lst8 GO:0032535 regulation of cellular component size ARBA:ARBA00028855 MODIFY general (21-200) 70 NEEDS_MORE_SPECIFIC true but uninformative replacement term Correct but general; the supported specific process is positive regulation of cell size, which Lst8 already carries. DROME/Lst8 GO:0038203 TORC2 signaling ARBA:ARBA00089220 ACCEPT leaf (0) 0 DROME/Lst8 GO:0051897 positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction ARBA:ARBA00089771 ACCEPT leaf (0) 0 DROME/Mef2 GO:0000981 DNA-binding transcription factor activity, RNA polymerase II-specific ARBA:ARBA00029016 ACCEPT specific (1-20) 8 DROME/Mef2 GO:0030154 cell differentiation ARBA:ARBA00027429 ACCEPT very general (>200 descendants) 1345 DROME/Mef2 GO:0160108 animal gross anatomical part developmental process ARBA:ARBA00098139 KEEP_AS_NON_CORE very general (>200 descendants) 3010 DROME/Mettl1 GO:0106143 tRNA (m7G46) methyltransferase complex ARBA:ARBA00091188 ACCEPT leaf (0) 0 DROME/Mtpbeta GO:0003988 acetyl-CoA C-acyltransferase activity ARBA:ARBA00043303 ACCEPT specific (1-20) 2 DROME/N GO:0001708 cell fate specification ARBA:ARBA00089615 KEEP_AS_NON_CORE general (21-200) 55 DROME/N GO:0002164 larval development ARBA:ARBA00043484 KEEP_AS_NON_CORE general (21-200) 27 DROME/N GO:0005829 cytosol ARBA:ARBA00029243 KEEP_AS_NON_CORE general (21-200) 73 DROME/N GO:0005911 cell-cell junction ARBA:ARBA00028427 KEEP_AS_NON_CORE general (21-200) 38 DROME/N GO:0007411 axon guidance ARBA:ARBA00026528 KEEP_AS_NON_CORE general (21-200) 46 DROME/N GO:0007422 peripheral nervous system development ARBA:ARBA00084148 KEEP_AS_NON_CORE specific (1-20) 19 DROME/N GO:0007424 open tracheal system development ARBA:ARBA00084149 KEEP_AS_NON_CORE general (21-200) 22 DROME/N GO:0007476 imaginal disc-derived wing morphogenesis ARBA:ARBA00084208 KEEP_AS_NON_CORE specific (1-20) 17 DROME/N GO:0007498 mesoderm development ARBA:ARBA00084318 KEEP_AS_NON_CORE general (21-200) 51 DROME/N GO:0007548 sex differentiation ARBA:ARBA00028749 KEEP_AS_NON_CORE general (21-200) 68 DROME/N GO:0008284 positive regulation of cell population proliferation ARBA:ARBA00027538 KEEP_AS_NON_CORE general (21-200) 85 DROME/N GO:0008347 glial cell migration ARBA:ARBA00092002 KEEP_AS_NON_CORE general (21-200) 23 DROME/N GO:0009792 embryo development ending in birth or egg hatching ARBA:ARBA00029005 KEEP_AS_NON_CORE general (21-200) 122 DROME/N GO:0009952 anterior/posterior pattern specification ARBA:ARBA00027259 KEEP_AS_NON_CORE general (21-200) 74 DROME/N GO:0009953 dorsal/ventral pattern formation ARBA:ARBA00027261 KEEP_AS_NON_CORE general (21-200) 28 DROME/N GO:0009986 cell surface ARBA:ARBA00027349 ACCEPT specific (1-20) 14 DROME/N GO:0010001 glial cell differentiation ARBA:ARBA00091307 KEEP_AS_NON_CORE general (21-200) 52 DROME/N GO:0010160 formation of animal organ boundary ARBA:ARBA00090996 KEEP_AS_NON_CORE specific (1-20) 5 DROME/N GO:0010631 epithelial cell migration ARBA:ARBA00091862 KEEP_AS_NON_CORE specific (1-20) 12 DROME/N GO:0012505 endomembrane system ARBA:ARBA00028953 KEEP_AS_NON_CORE very general (>200 descendants) 357 DROME/N GO:0016318 ommatidial rotation ARBA:ARBA00086689 KEEP_AS_NON_CORE leaf (0) 0 DROME/N GO:0019899 enzyme binding ARBA:ARBA00026481 REMOVE general (21-200) 77 TOO_GENERAL true but uninformative manual TOO_GENERAL The term is uninformative about Notch function; the relevant interactions (with Su(H), ligands, E3 ligases) are captured by more specific receptor and coactivator terms. Removal does not imply the underlying interactions are false. DROME/N GO:0019904 protein domain specific binding ARBA:ARBA00087321 REMOVE general (21-200) 79 TOO_GENERAL true but uninformative manual TOO_GENERAL The term is uninformative about Notch function; the relevant interactions (with Su(H), ligands, E3 ligases) are captured by more specific receptor and coactivator terms. Removal does not imply the underlying interactions are false. DROME/N GO:0022407 regulation of cell-cell adhesion ARBA:ARBA00028251 KEEP_AS_NON_CORE general (21-200) 158 DROME/N GO:0030097 hemopoiesis ARBA:ARBA00028409 KEEP_AS_NON_CORE general (21-200) 161 DROME/N GO:0030855 epithelial cell differentiation ARBA:ARBA00027967 KEEP_AS_NON_CORE very general (>200 descendants) 240 DROME/N GO:0035222 wing disc pattern formation ARBA:ARBA00091788 KEEP_AS_NON_CORE specific (1-20) 3 DROME/N GO:0035239 tube morphogenesis ARBA:ARBA00091780 KEEP_AS_NON_CORE very general (>200 descendants) 231 DROME/N GO:0035282 segmentation ARBA:ARBA00091150 KEEP_AS_NON_CORE general (21-200) 78 DROME/N GO:0038023 signaling receptor activity ARBA:ARBA00027254 MODIFY very general (>200 descendants) 389 NEEDS_MORE_SPECIFIC true but uninformative replacement term Correct but less informative than the experimentally supported transmembrane signaling receptor activity (GO:0004888), which is already annotated from direct evidence; propose the more specific term. DROME/N GO:0040008 regulation of growth ARBA:ARBA00026674 KEEP_AS_NON_CORE general (21-200) 169 DROME/N GO:0042659 regulation of cell fate specification ARBA:ARBA00086800 KEEP_AS_NON_CORE general (21-200) 42 DROME/N GO:0045944 positive regulation of transcription by RNA polymerase II ARBA:ARBA00027996 ACCEPT specific (1-20) 12 DROME/N GO:0048056 R3/R4 cell differentiation ARBA:ARBA00043632 KEEP_AS_NON_CORE specific (1-20) 2 DROME/N GO:0048565 digestive tract development ARBA:ARBA00091747 KEEP_AS_NON_CORE general (21-200) 56 DROME/N GO:0048568 embryonic organ development ARBA:ARBA00029173 KEEP_AS_NON_CORE general (21-200) 105 DROME/N GO:0048598 embryonic morphogenesis ARBA:ARBA00043386 KEEP_AS_NON_CORE very general (>200 descendants) 256 DROME/N GO:0048608 reproductive structure development ARBA:ARBA00028277 KEEP_AS_NON_CORE very general (>200 descendants) 238 DROME/N GO:0048663 neuron fate commitment ARBA:ARBA00043411 KEEP_AS_NON_CORE general (21-200) 48 DROME/N GO:0048732 gland development ARBA:ARBA00043366 KEEP_AS_NON_CORE general (21-200) 146 DROME/N GO:0048863 stem cell differentiation ARBA:ARBA00090702 KEEP_AS_NON_CORE general (21-200) 37 DROME/N GO:0050768 negative regulation of neurogenesis ARBA:ARBA00089677 KEEP_AS_NON_CORE general (21-200) 22 DROME/N GO:0050769 positive regulation of neurogenesis ARBA:ARBA00089675 KEEP_AS_NON_CORE general (21-200) 23 DROME/N GO:0050877 nervous system process ARBA:ARBA00029146 KEEP_AS_NON_CORE general (21-200) 194 DROME/N GO:0120035 regulation of plasma membrane bounded cell projection organization ARBA:ARBA00028050 KEEP_AS_NON_CORE general (21-200) 122 DROME/N GO:1990433 CSL-Notch-Mastermind transcription factor complex ARBA:ARBA00090083 ACCEPT leaf (0) 0 DROME/NTPase GO:0004382 GDP phosphatase activity ARBA:ARBA00086771 ACCEPT leaf (0) 0 DROME/NTPase GO:0005576 extracellular region ARBA:ARBA00027128 UNDECIDED very general (>200 descendants) 276 DROME/NTPase GO:0005794 Golgi apparatus ARBA:ARBA00028708 UNDECIDED general (21-200) 48 DROME/NTPase GO:0005886 plasma membrane ARBA:ARBA00027801 UNDECIDED very general (>200 descendants) 415 DROME/NTPase GO:0036384 CDP phosphatase activity ARBA:ARBA00089440 MARK_AS_OVER_ANNOTATED leaf (0) 0 UNCLASSIFIED unclassified The primary substrate comparison identifies GDP, UDP and IDP as efficient substrates and other NDP/NTP as poor substrates. A weak in-vitro side reaction should not be presented as the core physiological specificity. DROME/NTPase GO:0045134 UDP phosphatase activity ARBA:ARBA00092858 ACCEPT leaf (0) 0 DROME/NTPase GO:1990003 IDP phosphatase activity ARBA:ARBA00087262 ACCEPT leaf (0) 0 DROME/Nmnat GO:0009165 nucleotide biosynthetic process ARBA:ARBA00027613 ACCEPT general (21-200) 114 DROME/Nmnat GO:0070566 adenylyltransferase activity ARBA:ARBA00028518 ACCEPT general (21-200) 23 DROME/Nprl2 GO:1904262 negative regulation of TORC1 signaling ARBA:ARBA00026776 ACCEPT leaf (0) 0 DROME/P28159 GO:0000122 negative regulation of transcription by RNA polymerase II ARBA:ARBA00029133 ACCEPT specific (1-20) 10 DROME/P28159 GO:0005667 transcription regulator complex ARBA:ARBA00026399 ACCEPT general (21-200) 84 DROME/P28159 GO:0007219 Notch signaling pathway ARBA:ARBA00028179 ACCEPT specific (1-20) 5 DROME/P28159 GO:0048513 animal organ development ARBA:ARBA00029247 KEEP_AS_NON_CORE very general (>200 descendants) 1888 DROME/PNPase GO:0005737 cytoplasm ARBA:ARBA00026971 MARK_AS_OVER_ANNOTATED very general (>200 descendants) 1146 TOO_GENERAL true but uninformative generic The rule reflects bacterial PNPases. Mitochondria are formally part of the cytoplasm in GO, but the fly protein functions inside mitochondria in the degradosome, so this generic assignment adds nothing and can be misread as a cytosolic location. DROME/Pcf11 GO:0010467 gene expression ARBA:ARBA00028330 UNDECIDED very general (>200 descendants) 724 DROME/Pcf11 GO:0032991 protein-containing complex ARBA:ARBA00028902 UNDECIDED very general (>200 descendants) 2083 DROME/Pde4 GO:0001661 conditioned taste aversion ARBA:ARBA00089914 KEEP_AS_NON_CORE leaf (0) 0 DROME/Pde4 GO:0007268 chemical synaptic transmission ARBA:ARBA00028185 ACCEPT general (21-200) 69 DROME/Pde4 GO:0007614 short-term memory ARBA:ARBA00086035 KEEP_AS_NON_CORE leaf (0) 0 DROME/Pde4 GO:0007615 anesthesia-resistant memory ARBA:ARBA00086036 KEEP_AS_NON_CORE leaf (0) 0 DROME/Pde4 GO:0007619 courtship behavior ARBA:ARBA00044433 UNDECIDED specific (1-20) 8 DROME/Pde4 GO:0007623 circadian rhythm ARBA:ARBA00027901 UNDECIDED specific (1-20) 19 DROME/Pde4 GO:0008355 olfactory learning ARBA:ARBA00091941 KEEP_AS_NON_CORE leaf (0) 0 DROME/Pde4 GO:0040040 thermosensory behavior ARBA:ARBA00086785 KEEP_AS_NON_CORE leaf (0) 0 DROME/Pde4 GO:0046958 nonassociative learning ARBA:ARBA00084710 UNDECIDED specific (1-20) 3 DROME/Pde4 GO:0048675 axon extension ARBA:ARBA00091396 KEEP_AS_NON_CORE specific (1-20) 2 DROME/Pdk1 GO:0048638 regulation of developmental growth ARBA:ARBA00091468 KEEP_AS_NON_CORE general (21-200) 111 DROME/Pdk1 GO:1901701 cellular response to oxygen-containing compound ARBA:ARBA00027483 UNDECIDED very general (>200 descendants) 308 DROME/Pld GO:0006629 lipid metabolic process ARBA:ARBA00028591 KEEP_AS_NON_CORE very general (>200 descendants) 608 DROME/PolG1 GO:0006281 DNA repair ARBA:ARBA00029008 KEEP_AS_NON_CORE general (21-200) 74 DROME/PolG1 GO:0042575 DNA polymerase complex ARBA:ARBA00027252 MODIFY specific (1-20) 12 NEEDS_MORE_SPECIFIC true but uninformative replacement term Generic parent of GO:0005760 gamma DNA polymerase complex, which the gene already carries. DROME/PolG1 GO:0071897 DNA biosynthetic process ARBA:ARBA00028515 MODIFY general (21-200) 31 NEEDS_MORE_SPECIFIC true but uninformative replacement term Correct but generic; replaced by GO:0006264 mitochondrial DNA replication, which the gene already carries. DROME/Pp2A-29B GO:0000159 protein phosphatase type 2A complex ARBA:ARBA00090438 ACCEPT leaf (0) 0 DROME/Pp2A-29B GO:0005737 cytoplasm ARBA:ARBA00026971 ACCEPT very general (>200 descendants) 1146 DROME/Prx4 GO:0008340 determination of adult lifespan ARBA:ARBA00026742 MARK_AS_OVER_ANNOTATED leaf (0) 0 UNCLASSIFIED unclassified Knockdown of Prx4 by up to 90% had no effect on longevity; overexpression effects are mixed (low-level, under 2-fold, overexpression only tended to increase longevity, while higher overexpression was detrimental), so a lifespan-determining role is not established and the ARBA-derived term is an over-annotation. DROME/Prx4 GO:0019725 cellular homeostasis ARBA:ARBA00027105 KEEP_AS_NON_CORE general (21-200) 125 DROME/Prx4 GO:0042744 hydrogen peroxide catabolic process ARBA:ARBA00088409 ACCEPT specific (1-20) 1 DROME/Raf GO:0009791 post-embryonic development ARBA:ARBA00029007 KEEP_AS_NON_CORE very general (>200 descendants) 271 DROME/Rel GO:0000977 RNA polymerase II transcription regulatory region sequence-specific DNA binding ARBA:ARBA00028973 ACCEPT specific (1-20) 15 DROME/Rel GO:0006357 regulation of transcription by RNA polymerase II ARBA:ARBA00028137 ACCEPT general (21-200) 56 DROME/Rel GO:0048468 cell development ARBA:ARBA00028665 MARK_AS_OVER_ANNOTATED very general (>200 descendants) 672 INDIRECT_EFFECT overreach secondary These generic developmental terms are not specific to Relish function; specific developmental observations (neural fate, dendrite morphology) are separately annotated from experiments and are themselves secondary roles. DROME/Rel GO:0048731 system development ARBA:ARBA00027702 MARK_AS_OVER_ANNOTATED very general (>200 descendants) 2438 INDIRECT_EFFECT overreach secondary These generic developmental terms are not specific to Relish function; specific developmental observations (neural fate, dendrite morphology) are separately annotated from experiments and are themselves secondary roles. DROME/Rel GO:0160108 animal gross anatomical part developmental process ARBA:ARBA00098139 MARK_AS_OVER_ANNOTATED very general (>200 descendants) 3010 INDIRECT_EFFECT overreach secondary These generic developmental terms are not specific to Relish function; specific developmental observations (neural fate, dendrite morphology) are separately annotated from experiments and are themselves secondary roles. DROME/RfC38 GO:0005694 chromosome ARBA:ARBA00026361 KEEP_AS_NON_CORE very general (>200 descendants) 204 DROME/RfC38 GO:0006271 DNA strand elongation involved in DNA replication ARBA:ARBA00028969 ACCEPT specific (1-20) 10 DROME/RfC38 GO:0006281 DNA repair ARBA:ARBA00029008 KEEP_AS_NON_CORE general (21-200) 74 DROME/RfC38 GO:0008094 ATP-dependent activity, acting on DNA ARBA:ARBA00029240 MODIFY general (21-200) 29 NEEDS_MORE_SPECIFIC true but uninformative replacement term Correct but a generic parent of GO:0003689 DNA clamp loader activity, which the evidence supports and which the gene already carries (as contributes_to, since the activity belongs to the RFC complex). DROME/RfC38 GO:0032991 protein-containing complex ARBA:ARBA00028902 MODIFY very general (>200 descendants) 2083 NEEDS_MORE_SPECIFIC true but uninformative replacement term Uninformative parent of the specific complexes GO:0005663 DNA replication factor C complex and GO:0031391 Elg1 RFC-like complex, both of which the gene already carries. DROME/RluA-1 GO:0006396 RNA processing ARBA:ARBA00028223 MODIFY very general (>200 descendants) 252 OTHER_TERM different term needed replacement term RNA interaction and modification are consistent with the conserved RluA-family enzyme. Pseudouridine synthase activity or its corresponding synthesis process captures the molecular role more precisely than generic RNA binding, processing or modification. DROME/Ser GO:0007166 cell surface receptor signaling pathway ARBA:ARBA00029053 MODIFY very general (>200 descendants) 403 NEEDS_MORE_SPECIFIC true but uninformative replacement term Correct but generic; Serrate acts specifically in the Notch signaling pathway (GO:0007219), already annotated with experimental evidence. DROME/Ser GO:0007435 salivary gland morphogenesis ARBA:ARBA00084159 KEEP_AS_NON_CORE specific (1-20) 9 DROME/Ser GO:0008587 imaginal disc-derived wing margin morphogenesis ARBA:ARBA00085082 KEEP_AS_NON_CORE specific (1-20) 1 DROME/Ser GO:0009986 cell surface ARBA:ARBA00027349 ACCEPT specific (1-20) 14 DROME/Ser GO:0016330 second mitotic wave involved in compound eye morphogenesis ARBA:ARBA00086657 KEEP_AS_NON_CORE leaf (0) 0 DROME/Ser GO:0030718 germ-line stem cell population maintenance ARBA:ARBA00088373 KEEP_AS_NON_CORE specific (1-20) 2 DROME/Ser GO:0035214 eye-antennal disc development ARBA:ARBA00091693 KEEP_AS_NON_CORE specific (1-20) 10 DROME/Ser GO:0036011 imaginal disc-derived leg segmentation ARBA:ARBA00090233 KEEP_AS_NON_CORE specific (1-20) 1 DROME/Ser GO:0042063 gliogenesis ARBA:ARBA00086246 KEEP_AS_NON_CORE general (21-200) 83 DROME/Ser GO:0043005 neuron projection ARBA:ARBA00027418 KEEP_AS_NON_CORE general (21-200) 135 DROME/Ser GO:0043208 glycosphingolipid binding ARBA:ARBA00086545 KEEP_AS_NON_CORE specific (1-20) 6 DROME/Ser GO:0045179 apical cortex ARBA:ARBA00092806 KEEP_AS_NON_CORE specific (1-20) 2 DROME/Ser GO:0046331 lateral inhibition ARBA:ARBA00093161 ACCEPT leaf (0) 0 DROME/Ser GO:0048018 receptor ligand activity ARBA:ARBA00028558 ACCEPT general (21-200) 34 DROME/Ser GO:0048100 wing disc anterior/posterior pattern formation ARBA:ARBA00089998 KEEP_AS_NON_CORE leaf (0) 0 DROME/Ser GO:0048468 cell development ARBA:ARBA00028665 KEEP_AS_NON_CORE very general (>200 descendants) 672 DROME/Ser GO:0051093 negative regulation of developmental process ARBA:ARBA00027583 KEEP_AS_NON_CORE very general (>200 descendants) 504 DROME/Ser GO:0051239 regulation of multicellular organismal process ARBA:ARBA00028859 KEEP_AS_NON_CORE very general (>200 descendants) 1807 DROME/Smurf GO:0005737 cytoplasm ARBA:ARBA00026971 ACCEPT very general (>200 descendants) 1146 DROME/Smurf GO:0030154 cell differentiation ARBA:ARBA00027429 MARK_AS_OVER_ANNOTATED very general (>200 descendants) 1345 TOO_GENERAL true but uninformative Generic Generic developmental terms that do not describe Smurf's function; specific developmental roles are annotated from experiments. DROME/Smurf GO:0045879 negative regulation of smoothened signaling pathway ARBA:ARBA00086554 ACCEPT specific (1-20) 1 DROME/Smurf GO:0048260 positive regulation of receptor-mediated endocytosis ARBA:ARBA00089728 KEEP_AS_NON_CORE specific (1-20) 4 DROME/Smurf GO:0160108 animal gross anatomical part developmental process ARBA:ARBA00098139 MARK_AS_OVER_ANNOTATED very general (>200 descendants) 3010 TOO_GENERAL true but uninformative Generic Generic developmental terms that do not describe Smurf's function; specific developmental roles are annotated from experiments. DROME/Snx1 GO:0005737 cytoplasm ARBA:ARBA00026971 MODIFY very general (>200 descendants) 1146 NEEDS_MORE_SPECIFIC true but uninformative replacement term Correct but much less specific than the evidence supports: Snx1 is a peripheral endosome membrane protein, and endosome (GO:0005768) is already annotated to Snx1 (ISS) along with more specific endosome membrane terms. DROME/Snx1 GO:0016020 membrane ARBA:ARBA00028763 MODIFY very general (>200 descendants) 895 NEEDS_MORE_SPECIFIC true but uninformative replacement term Correct but much less specific than the evidence supports: Snx1 is a peripheral endosome membrane protein, and endosome (GO:0005768) is already annotated to Snx1 (ISS) along with more specific endosome membrane terms. DROME/Sqor GO:0070224 sulfide:quinone oxidoreductase activity ARBA:ARBA00092407 MODIFY leaf (0) 0 OTHER_TERM different term needed replacement term As for the IBA row; replace with the glutathione-dependent activity GO:0106436. DROME/Stim GO:0002115 store-operated calcium entry ARBA:ARBA00087659 ACCEPT leaf (0) 0 DROME/Su-var-2-10 GO:0005694 chromosome ARBA:ARBA00026361 ACCEPT very general (>200 descendants) 204 DROME/Su-var-2-10 GO:0016746 acyltransferase activity ARBA:ARBA00027718 MODIFY very general (>200 descendants) 441 NEEDS_MORE_SPECIFIC true but uninformative replacement term Su(var)2-10 is an SP-RING SUMO E3 ligase whose activity depends on Cys341 of the SP-RING, and it mediates SUMOylation of the substrate Bonus. The informative term is SUMO ligase activity. DROME/Su-var-2-10 GO:0097240 chromosome attachment to the nuclear envelope ARBA:ARBA00089802 KEEP_AS_NON_CORE specific (1-20) 6 DROME/Su-var-2-10 GO:0140096 catalytic activity, acting on a protein ARBA:ARBA00027983 MODIFY very general (>200 descendants) 629 NEEDS_MORE_SPECIFIC true but uninformative replacement term The specific, experimentally supported activity is SUMO ligase activity (SP-RING C341S abolishes Su(var)2-10 E3 activity). DROME/Tace GO:0006509 membrane protein ectodomain proteolysis ARBA:ARBA00085430 ACCEPT specific (1-20) 1 DROME/Tl GO:0016020 membrane ARBA:ARBA00028763 ACCEPT very general (>200 descendants) 895 DROME/Tmlh GO:0016706 2-oxoglutarate-dependent dioxygenase activity ARBA:ARBA00027633 MODIFY general (21-200) 65 NEEDS_MORE_SPECIFIC true but uninformative replacement term Correct family-level activity, but the specific reaction is known by orthology and is already annotated: trimethyllysine dioxygenase activity (GO:0050353), a descendant of this term. DROME/Toll-7 GO:0009653 anatomical structure morphogenesis ARBA:ARBA00026583 KEEP_AS_NON_CORE very general (>200 descendants) 1501 DROME/Toll-7 GO:0048666 neuron development ARBA:ARBA00028378 ACCEPT general (21-200) 186 DROME/TyrRS GO:0006950 response to stress ARBA:ARBA00026300 MODIFY very general (>200 descendants) 590 NEEDS_MORE_SPECIFIC true but uninformative replacement term PMID:26658841 Figure 3 detects TyrRS-HA secretion from serum-deprived S2 cells and controls for cellular contamination and membrane damage. This supports a cellular response to nourishment deprivation, without establishing whole-animal starvation survival or a mammalian PARP1 mechanism. DROME/Vps29 GO:0005768 endosome ARBA:ARBA00028568 ACCEPT general (21-200) 68 DROME/Vps29 GO:0098796 membrane protein complex ARBA:ARBA00028844 MODIFY very general (>200 descendants) 543 NEEDS_MORE_SPECIFIC true but uninformative replacement term Correct but uninformative; retromer, cargo-selective complex (GO:0030906) is already annotated to Vps29 (ISS). DROME/alc GO:0005737 cytoplasm ARBA:ARBA00026971 ACCEPT very general (>200 descendants) 1146 DROME/amon GO:0016486 peptide hormone processing ARBA:ARBA00043631 ACCEPT specific (1-20) 9 DROME/amon GO:0030537 larval behavior ARBA:ARBA00086961 KEEP_AS_NON_CORE specific (1-20) 6 DROME/aub GO:0007279 pole cell formation ARBA:ARBA00085029 ACCEPT leaf (0) 0 DROME/aub GO:0009994 oocyte differentiation ARBA:ARBA00084567 KEEP_AS_NON_CORE general (21-200) 34 DROME/aub GO:0016891 RNA endonuclease activity producing 5'-phosphomonoesters, hydrolytic mechanism ARBA:ARBA00028553 ACCEPT specific (1-20) 15 DROME/aub GO:0031507 heterochromatin formation ARBA:ARBA00033536 MARK_AS_OVER_ANNOTATED general (21-200) 25 INDIRECT_EFFECT overreach indirect Aub is cytoplasmic; effects of aub mutations on heterochromatic silencing are indirect (loss of piRNAs available to nuclear Piwi). Aub does not act at chromatin. DROME/aub GO:0034584 piRNA binding ARBA:ARBA00092433 ACCEPT leaf (0) 0 DROME/aub GO:0043186 P granule ARBA:ARBA00026989 ACCEPT specific (1-20) 2 DROME/aub GO:0140965 secondary piRNA processing ARBA:ARBA00087010 ACCEPT leaf (0) 0 DROME/aub GO:0141009 transposable element silencing by piRNA-mediated mRNA destabilization ARBA:ARBA00092222 ACCEPT leaf (0) 0 DROME/aurB GO:0000280 nuclear division ARBA:ARBA00028466 MODIFY general (21-200) 120 NEEDS_MORE_SPECIFIC true but uninformative replacement term Correct but general (ARBA rule); the specific process supported by fly evidence is mitotic sister chromatid segregation (GO:0000070), which aurB already carries. DROME/aurB GO:0000776 kinetochore ARBA:ARBA00027576 ACCEPT specific (1-20) 11 DROME/aurB GO:0000819 sister chromatid segregation ARBA:ARBA00026649 MODIFY general (21-200) 29 NEEDS_MORE_SPECIFIC true but uninformative replacement term Correct but general (ARBA rule); replace with the more specific mitotic sister chromatid segregation (GO:0000070), already carried by aurB with IMP evidence. DROME/aurB GO:0032133 chromosome passenger complex ARBA:ARBA00085347 ACCEPT leaf (0) 0 DROME/aurB GO:0051233 spindle midzone ARBA:ARBA00089348 ACCEPT specific (1-20) 2 DROME/betaTub97EF GO:0009653 anatomical structure morphogenesis ARBA:ARBA00026583 KEEP_AS_NON_CORE very general (>200 descendants) 1501 DROME/betaTub97EF GO:0048731 system development ARBA:ARBA00027702 KEEP_AS_NON_CORE very general (>200 descendants) 2438 DROME/betaTub97EF GO:0160108 animal gross anatomical part developmental process ARBA:ARBA00098139 KEEP_AS_NON_CORE very general (>200 descendants) 3010 DROME/boi GO:0007155 cell adhesion ARBA:ARBA00028946 MODIFY general (21-200) 88 NEEDS_MORE_SPECIFIC true but uninformative replacement term Correct but general; cell-cell adhesion is already annotated to Boi (IBA) and is as specific as the Boi evidence allows. DROME/boi GO:0048513 animal organ development ARBA:ARBA00029247 MODIFY very general (>200 descendants) 1888 NEEDS_MORE_SPECIFIC true but uninformative replacement term Correct but very general; the specific developmental process supported experimentally is compound eye development, which Boi already carries (IGI, PMID:21044292). DROME/boi GO:0048731 system development ARBA:ARBA00027702 MODIFY very general (>200 descendants) 2438 NEEDS_MORE_SPECIFIC true but uninformative replacement term Correct but very general; the specific developmental process supported experimentally is compound eye development, which Boi already carries (IGI, PMID:21044292). DROME/cdm GO:0006606 protein import into nucleus ARBA:ARBA00028627 ACCEPT specific (1-20) 2 DROME/ci GO:0000122 negative regulation of transcription by RNA polymerase II ARBA:ARBA00029133 ACCEPT specific (1-20) 10 DROME/ci GO:0140297 DNA-binding transcription factor binding ARBA:ARBA00026336 REMOVE specific (1-20) 20 WRONG_ACTIVITY wrong manual WRONG_ACTIVITY Removed. No characterised Drosophila Ci partner is a DNA-binding transcription factor: the documented partners are Costal-2 (a kinesin-related protein), Fused (a kinase), Suppressor of fused, Slimb and Roadkill/HIB (ubiquitin ligase substrate receptors), nejire/CBP and Taiman/NCOA2 (coactivators), Hyrax (a PAF1 subunit) and Rbfox1 (an RNA-binding protein). The only partner of Ci that is itself a DNA-binding transcription factor is Ci, and that self-association is already stated precisely by GO:0042803. The electronic rule therefore adds no information about this protein and asserts a partner class that has not been demonstrated for it. DROME/cos GO:0015630 microtubule cytoskeleton ARBA:ARBA00029268 MODIFY general (21-200) 108 NEEDS_MORE_SPECIFIC true but uninformative replacement term Correct but general; Cos2 binds microtubules directly, so the specific location is microtubule, which Cos2 already carries (IBA row). DROME/cpa GO:0015629 actin cytoskeleton ARBA:ARBA00029230 ACCEPT general (21-200) 89 DROME/cpa GO:0032991 protein-containing complex ARBA:ARBA00028902 KEEP_AS_NON_CORE very general (>200 descendants) 2083 DROME/cpb GO:0015629 actin cytoskeleton ARBA:ARBA00029230 ACCEPT general (21-200) 89 DROME/dl GO:0000977 RNA polymerase II transcription regulatory region sequence-specific DNA binding ARBA:ARBA00028973 ACCEPT specific (1-20) 15 DROME/dl GO:0001228 DNA-binding transcription activator activity, RNA polymerase II-specific ARBA:ARBA00027759 ACCEPT leaf (0) 0 DROME/dl GO:0002225 positive regulation of antimicrobial peptide production ARBA:ARBA00087827 KEEP_AS_NON_CORE specific (1-20) 10 DROME/dl GO:0005654 nucleoplasm ARBA:ARBA00026290 ACCEPT general (21-200) 65 DROME/dl GO:0007249 canonical NF-kappaB signal transduction ARBA:ARBA00085080 KEEP_AS_NON_CORE specific (1-20) 2 DROME/dl GO:0008063 Toll signaling pathway ARBA:ARBA00093120 ACCEPT leaf (0) 0 DROME/dl GO:0035206 regulation of hemocyte proliferation ARBA:ARBA00091713 KEEP_AS_NON_CORE specific (1-20) 2 DROME/dl GO:0045087 innate immune response ARBA:ARBA00027946 ACCEPT general (21-200) 39 DROME/dl GO:0048935 peripheral nervous system neuron development ARBA:ARBA00092968 KEEP_AS_NON_CORE specific (1-20) 2 DROME/drk GO:0005154 epidermal growth factor receptor binding ARBA:ARBA00085861 ACCEPT leaf (0) 0 DROME/drk GO:0007173 epidermal growth factor receptor signaling pathway ARBA:ARBA00034174 ACCEPT specific (1-20) 3 DROME/drk GO:0009653 anatomical structure morphogenesis ARBA:ARBA00026583 MARK_AS_OVER_ANNOTATED very general (>200 descendants) 1501 INDIRECT_EFFECT overreach phenotype This is a very broad developmental ancestor of several Drk RTK-signaling phenotypes. The term is not false, but it loses pathway specificity and should not be emphasized as a Drk function. DROME/drk GO:0048468 cell development ARBA:ARBA00028665 MARK_AS_OVER_ANNOTATED very general (>200 descendants) 672 INDIRECT_EFFECT overreach phenotype The assertion is only a broad ancestor of multiple tissue-specific Drk phenotypes and should be represented, when needed, by the specific RTK pathways rather than a generic developmental process term. DROME/drk GO:0160108 animal gross anatomical part developmental process ARBA:ARBA00098139 MARK_AS_OVER_ANNOTATED very general (>200 descendants) 3010 INDIRECT_EFFECT overreach phenotype This ARBA term is a very broad developmental roll-up of Drk phenotypes. It is not a useful direct functional annotation for a receptor-proximal adaptor. DROME/eIF4E1 GO:0000340 RNA 7-methylguanosine cap binding ARBA:ARBA00027684 ACCEPT leaf (0) 0 DROME/eRF1 GO:0005829 cytosol ARBA:ARBA00029243 ACCEPT general (21-200) 73 DROME/eRF3 GO:0003747 translation release factor activity ARBA:ARBA00089166 MODIFY specific (1-20) 2 NEEDS_MORE_SPECIFIC true but uninformative replacement term "eRF3 is the GTPase partner of eRF1 in the termination complex that releases nascent chains; genetic loss of eRF3 causes stop-codon readthrough. Stop-codon recognition is done by eRF1 (whose parent term is refined to the codon-specific child GO:0016149), so for symmetry the eRF3 row is refined to the codon-nonspecific sibling, whose definition (""not specific to particular codons; binds to guanine nucleotides"") describes the class II factor. Note that experimental curation of the orthologs (human GSPT1/GSPT2, yeast SUP35) uses the parent GO:0003747, so the refinement is a proposal, not a correction of an error. GOA records the qualifier as enables, whereas the activity is exerted jointly with eRF1 (contributes_to would be more accurate)." DROME/eRF3 GO:0005829 cytosol ARBA:ARBA00029243 ACCEPT general (21-200) 73 DROME/eRF3 GO:0018444 translation release factor complex ARBA:ARBA00085781 ACCEPT leaf (0) 0 DROME/enok GO:0003824 catalytic activity ARBA:ARBA00027533 MODIFY very general (>200 descendants) 6405 NEEDS_MORE_SPECIFIC true but uninformative replacement term Correct but uninformative; replace with GO:0043994 histone H3K23 acetyltransferase activity, already annotated by IDA. DROME/enok GO:0040029 epigenetic regulation of gene expression ARBA:ARBA00033485 MODIFY general (21-200) 44 OTHER_TERM different term needed replacement term Correct but general; Enok's H3K23 acetylation activates transcription. Replace with GO:0045944 positive regulation of transcription by RNA polymerase II, already annotated by IMP. DROME/enok GO:0070775 H3 histone acetyltransferase complex ARBA:ARBA00084418 MODIFY specific (1-20) 7 NEEDS_MORE_SPECIFIC true but uninformative replacement term Correct but general; replace with GO:0070776 MOZ/MORF histone acetyltransferase complex, its descendant, already annotated. DROME/ey GO:0009791 post-embryonic development ARBA:ARBA00029007 ACCEPT very general (>200 descendants) 271 DROME/ey GO:0030154 cell differentiation ARBA:ARBA00027429 ACCEPT very general (>200 descendants) 1345 DROME/ey GO:0045944 positive regulation of transcription by RNA polymerase II ARBA:ARBA00027996 ACCEPT specific (1-20) 12 DROME/ey GO:0048731 system development ARBA:ARBA00027702 ACCEPT very general (>200 descendants) 2438 DROME/ey GO:0090596 sensory organ morphogenesis ARBA:ARBA00043576 ACCEPT general (21-200) 116 DROME/ftz-f1 GO:0000981 DNA-binding transcription factor activity, RNA polymerase II-specific ARBA:ARBA00029016 ACCEPT specific (1-20) 8 DROME/ftz-f1 GO:0035556 intracellular signal transduction ARBA:ARBA00026887 MODIFY general (21-200) 195 NEEDS_MORE_SPECIFIC true but uninformative replacement term BetaFTZ-F1 confers competence for the ecdysone-triggered developmental transcriptional response (PMID:7954827). Intracellular receptor signaling pathway describes this role more precisely than unrestricted intracellular signal transduction. The support comes from the developmental experiments, not agreement with the ARBA assertion. DROME/fu GO:0005737 cytoplasm ARBA:ARBA00026971 ACCEPT very general (>200 descendants) 1146 DROME/hairy GO:1990837 sequence-specific double-stranded DNA binding ARBA:ARBA00028376 ACCEPT general (21-200) 48 DROME/hbs GO:0009653 anatomical structure morphogenesis ARBA:ARBA00026583 KEEP_AS_NON_CORE very general (>200 descendants) 1501 DROME/hbs GO:0030154 cell differentiation ARBA:ARBA00027429 KEEP_AS_NON_CORE very general (>200 descendants) 1345 DROME/hbs GO:0160108 animal gross anatomical part developmental process ARBA:ARBA00098139 KEEP_AS_NON_CORE very general (>200 descendants) 3010 DROME/hh GO:0030154 cell differentiation ARBA:ARBA00027429 KEEP_AS_NON_CORE very general (>200 descendants) 1345 DROME/hh GO:0048731 system development ARBA:ARBA00027702 KEEP_AS_NON_CORE very general (>200 descendants) 2438 DROME/hh GO:0160108 animal gross anatomical part developmental process ARBA:ARBA00098139 KEEP_AS_NON_CORE very general (>200 descendants) 3010 DROME/ihog GO:0007155 cell adhesion ARBA:ARBA00028946 MODIFY general (21-200) 88 NEEDS_MORE_SPECIFIC true but uninformative replacement term Correct but general; homotypic cell-cell adhesion is already annotated to Ihog (IDA, PMID:31209108). DROME/ihog GO:0048513 animal organ development ARBA:ARBA00029247 MODIFY very general (>200 descendants) 1888 NEEDS_MORE_SPECIFIC true but uninformative replacement term Correct but very general; the specific developmental process supported experimentally is compound eye development, which Ihog already carries (IGI, PMID:21044292). DROME/ihog GO:0048731 system development ARBA:ARBA00027702 MODIFY very general (>200 descendants) 2438 NEEDS_MORE_SPECIFIC true but uninformative replacement term Correct but very general; the specific developmental process supported experimentally is compound eye development, which Ihog already carries (IGI, PMID:21044292). DROME/jar GO:0005737 cytoplasm ARBA:ARBA00026971 ACCEPT very general (>200 descendants) 1146 DROME/jar GO:0015629 actin cytoskeleton ARBA:ARBA00029230 ACCEPT general (21-200) 89 DROME/klg GO:0009653 anatomical structure morphogenesis ARBA:ARBA00026583 ACCEPT very general (>200 descendants) 1501 DROME/klg GO:0030154 cell differentiation ARBA:ARBA00027429 ACCEPT very general (>200 descendants) 1345 DROME/klg GO:0160108 animal gross anatomical part developmental process ARBA:ARBA00098139 ACCEPT very general (>200 descendants) 3010 DROME/kni GO:0048731 system development ARBA:ARBA00027702 KEEP_AS_NON_CORE very general (>200 descendants) 2438 DROME/kni GO:0160108 animal gross anatomical part developmental process ARBA:ARBA00098139 KEEP_AS_NON_CORE very general (>200 descendants) 3010 DROME/koi GO:0005635 nuclear envelope ARBA:ARBA00026328 ACCEPT general (21-200) 29 DROME/kuz GO:0005737 cytoplasm ARBA:ARBA00026971 MARK_AS_OVER_ANNOTATED very general (>200 descendants) 1146 TOO_GENERAL true but uninformative adds no Kuz is a single-pass type I transmembrane protease whose active pool is at the plasma membrane; it transits the secretory pathway. 'Cytoplasm' adds nothing and misrepresents a membrane protein. DROME/kuz GO:0005886 plasma membrane ARBA:ARBA00027801 ACCEPT very general (>200 descendants) 415 DROME/kuz GO:0043226 organelle ARBA:ARBA00029065 MARK_AS_OVER_ANNOTATED very general (>200 descendants) 1881 TOO_GENERAL true but uninformative Uninformative Uninformative high-level term; Kuz is a plasma membrane/secretory-pathway protein. DROME/loqs GO:0010468 regulation of gene expression ARBA:ARBA00028334 ACCEPT very general (>200 descendants) 874 DROME/loqs GO:0048477 oogenesis ARBA:ARBA00028681 KEEP_AS_NON_CORE general (21-200) 81 DROME/loqs GO:0070578 RISC-loading complex ARBA:ARBA00085164 ACCEPT leaf (0) 0 DROME/mTor GO:0004672 protein kinase activity ARBA:ARBA00027018 MODIFY general (21-200) 115 NEEDS_MORE_SPECIFIC true but uninformative replacement term Correct but general; mTor already carries protein serine/threonine kinase activity. DROME/mTor GO:0008340 determination of adult lifespan ARBA:ARBA00026742 KEEP_AS_NON_CORE leaf (0) 0 DROME/mTor GO:0008361 regulation of cell size ARBA:ARBA00091970 MODIFY general (21-200) 35 NEEDS_MORE_SPECIFIC true but uninformative replacement term Correct but general; the direction is known and mTor already carries positive regulation of cell size. DROME/mTor GO:0010507 negative regulation of autophagy ARBA:ARBA00043537 MODIFY specific (1-20) 10 NEEDS_MORE_SPECIFIC true but uninformative replacement term Correct but general; mTor already carries negative regulation of macroautophagy. DROME/mTor GO:0031929 TOR signaling ARBA:ARBA00086602 ACCEPT specific (1-20) 2 DROME/mTor GO:0031931 TORC1 complex ARBA:ARBA00026257 ACCEPT leaf (0) 0 DROME/mTor GO:0031932 TORC2 complex ARBA:ARBA00026254 ACCEPT leaf (0) 0 DROME/mTor GO:0045787 positive regulation of cell cycle ARBA:ARBA00026693 MARK_AS_OVER_ANNOTATED general (21-200) 118 TOO_GENERAL true but uninformative broad These broad grouping terms (cell cycle, transcription, developmental/multicellular/reproductive process, protein metabolic process) do not map to a single more specific process that mTor carries; the specific outputs (cell size, macroautophagy, Pol III transcription, meiotic entry) are annotated separately, and positive regulation of cell cycle conflicts with the TOR-dependent G2/M delay (PMID:17183368). DROME/mTor GO:0045893 positive regulation of DNA-templated transcription ARBA:ARBA00029082 MARK_AS_OVER_ANNOTATED general (21-200) 42 TOO_GENERAL true but uninformative broad These broad grouping terms (cell cycle, transcription, developmental/multicellular/reproductive process, protein metabolic process) do not map to a single more specific process that mTor carries; the specific outputs (cell size, macroautophagy, Pol III transcription, meiotic entry) are annotated separately, and positive regulation of cell cycle conflicts with the TOR-dependent G2/M delay (PMID:17183368). DROME/mTor GO:0045930 negative regulation of mitotic cell cycle ARBA:ARBA00044434 KEEP_AS_NON_CORE general (21-200) 32 DROME/mTor GO:0051094 positive regulation of developmental process ARBA:ARBA00027577 MARK_AS_OVER_ANNOTATED very general (>200 descendants) 467 TOO_GENERAL true but uninformative broad These broad grouping terms (cell cycle, transcription, developmental/multicellular/reproductive process, protein metabolic process) do not map to a single more specific process that mTor carries; the specific outputs (cell size, macroautophagy, Pol III transcription, meiotic entry) are annotated separately, and positive regulation of cell cycle conflicts with the TOR-dependent G2/M delay (PMID:17183368). DROME/mTor GO:0051240 positive regulation of multicellular organismal process ARBA:ARBA00028891 MARK_AS_OVER_ANNOTATED very general (>200 descendants) 565 TOO_GENERAL true but uninformative broad These broad grouping terms (cell cycle, transcription, developmental/multicellular/reproductive process, protein metabolic process) do not map to a single more specific process that mTor carries; the specific outputs (cell size, macroautophagy, Pol III transcription, meiotic entry) are annotated separately, and positive regulation of cell cycle conflicts with the TOR-dependent G2/M delay (PMID:17183368). DROME/mTor GO:0051246 regulation of protein metabolic process ARBA:ARBA00028884 MARK_AS_OVER_ANNOTATED very general (>200 descendants) 442 TOO_GENERAL true but uninformative broad These broad grouping terms (cell cycle, transcription, developmental/multicellular/reproductive process, protein metabolic process) do not map to a single more specific process that mTor carries; the specific outputs (cell size, macroautophagy, Pol III transcription, meiotic entry) are annotated separately, and positive regulation of cell cycle conflicts with the TOR-dependent G2/M delay (PMID:17183368). DROME/mTor GO:0051896 regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction ARBA:ARBA00089772 MODIFY specific (1-20) 2 NEEDS_MORE_SPECIFIC true but uninformative replacement term Correct but general; the direction is known (TORC2 activates Akt) and mTor already carries the positive regulation term. DROME/mTor GO:2000243 positive regulation of reproductive process ARBA:ARBA00028527 MARK_AS_OVER_ANNOTATED general (21-200) 108 TOO_GENERAL true but uninformative broad These broad grouping terms (cell cycle, transcription, developmental/multicellular/reproductive process, protein metabolic process) do not map to a single more specific process that mTor carries; the specific outputs (cell size, macroautophagy, Pol III transcription, meiotic entry) are annotated separately, and positive regulation of cell cycle conflicts with the TOR-dependent G2/M delay (PMID:17183368). DROME/metro GO:0030054 cell junction ARBA:ARBA00028333 ACCEPT general (21-200) 189 DROME/mle GO:0003723 RNA binding ARBA:ARBA00028406 MODIFY general (21-200) 163 NEEDS_MORE_SPECIFIC true but uninformative replacement term Correct but general; MLE binds the roX lncRNAs (and dsRNA stem-loops within them). Replace with GO:0106222 lncRNA binding, already annotated by IDA. DROME/mle GO:0040029 epigenetic regulation of gene expression ARBA:ARBA00033485 MODIFY general (21-200) 44 NEEDS_MORE_SPECIFIC true but uninformative replacement term Correct but general; MLE's role is in X-chromosome dosage compensation. Replace with GO:0009047, already annotated. DROME/mof GO:0005705 polytene chromosome interband ARBA:ARBA00086853 KEEP_AS_NON_CORE leaf (0) 0 DROME/mof GO:0010468 regulation of gene expression ARBA:ARBA00028334 MODIFY very general (>200 descendants) 874 NEEDS_MORE_SPECIFIC true but uninformative replacement term Correct but general; MOF positively regulates gene expression by depositing H4K16ac. Replace with GO:0141137 positive regulation of gene expression, epigenetic, already annotated to MOF by IDA. DROME/mof GO:0140861 DNA repair-dependent chromatin remodeling ARBA:ARBA00087263 KEEP_AS_NON_CORE leaf (0) 0 DROME/msl-1 GO:1902562 H4 histone acetyltransferase complex ARBA:ARBA00027022 MODIFY specific (1-20) 5 NEEDS_MORE_SPECIFIC true but uninformative replacement term Correct but general; MSL complex (GO:0072487) is the specific H4 acetyltransferase complex containing MSL1, already annotated. DROME/msl-3 GO:0010468 regulation of gene expression ARBA:ARBA00028334 MODIFY very general (>200 descendants) 874 NEEDS_MORE_SPECIFIC true but uninformative replacement term Correct but general; replace with GO:0009047 dosage compensation by hyperactivation of X chromosome, already annotated. DROME/msl-3 GO:0072487 MSL complex ARBA:ARBA00090469 ACCEPT leaf (0) 0 DROME/mtDNA-helicase GO:0006264 mitochondrial DNA replication ARBA:ARBA00086414 ACCEPT specific (1-20) 2 DROME/piwi GO:0004521 RNA endonuclease activity ARBA:ARBA00029225 KEEP_AS_NON_CORE general (21-200) 27 DROME/piwi GO:0007279 pole cell formation ARBA:ARBA00085029 KEEP_AS_NON_CORE leaf (0) 0 DROME/piwi GO:0009994 oocyte differentiation ARBA:ARBA00084567 KEEP_AS_NON_CORE general (21-200) 34 DROME/piwi GO:0010526 transposable element silencing ARBA:ARBA00092295 ACCEPT specific (1-20) 8 DROME/piwi GO:0031507 heterochromatin formation ARBA:ARBA00033536 ACCEPT general (21-200) 25 DROME/piwi GO:0034584 piRNA binding ARBA:ARBA00092433 ACCEPT leaf (0) 0 DROME/piwi GO:0034587 piRNA processing ARBA:ARBA00047257 ACCEPT specific (1-20) 2 DROME/piwi GO:0043186 P granule ARBA:ARBA00026989 KEEP_AS_NON_CORE specific (1-20) 2 DROME/piwi GO:0140991 piRNA-mediated gene silencing by mRNA destabilization ARBA:ARBA00087016 KEEP_AS_NON_CORE specific (1-20) 1 DROME/pll GO:0009791 post-embryonic development ARBA:ARBA00029007 MARK_AS_OVER_ANNOTATED very general (>200 descendants) 271 TOO_GENERAL true but uninformative broad Very broad. pll mutants show some zygotic lethality, but no specific post-embryonic developmental process has been attributed to Pelle; the annotation adds nothing beyond its signalling roles. DROME/pll GO:0031349 positive regulation of defense response ARBA:ARBA00028260 ACCEPT general (21-200) 156 DROME/pll GO:0045087 innate immune response ARBA:ARBA00027946 ACCEPT general (21-200) 39 DROME/pll GO:1902533 positive regulation of intracellular signal transduction ARBA:ARBA00027124 KEEP_AS_NON_CORE general (21-200) 89 DROME/rad50 GO:0000722 telomere maintenance via recombination ARBA:ARBA00027344 MODIFY specific (1-20) 1 OTHER_TERM different term needed replacement term Drosophila telomere length is maintained by HeT-A/TART retrotransposition; the documented role of fly Rad50 is telomere capping (HOAP/HP1 recruitment and fusion prevention), not recombination-based telomere lengthening. The telomere-maintenance core of the inference is sound, so, as for the IMP row, it is redirected to the sibling term telomere capping (both are is_a children of telomere maintenance), consistent with the GO:0000723 rows of all three MRN subunits. DROME/rdgBbeta GO:0005543 phospholipid binding ARBA:ARBA00027145 KEEP_AS_NON_CORE specific (1-20) 19 DROME/rdgBbeta GO:0005634 nucleus ARBA:ARBA00026330 REMOVE very general (>200 descendants) 473 WRONG_LOCATION wrong manual WRONG_LOCATION No published evidence supports nuclear localization for rdgBbeta or PITPNC1. The human ortholog was localized to the cytoplasm by immunofluorescence (PMID:10531358). The protein lacks nuclear localization signals. This ARBA prediction appears to be erroneous. DROME/rdgBbeta GO:0005737 cytoplasm ARBA:ARBA00026971 ACCEPT very general (>200 descendants) 1146 DROME/scat GO:0005737 cytoplasm ARBA:ARBA00026971 MODIFY very general (>200 descendants) 1146 NEEDS_MORE_SPECIFIC true but uninformative replacement term Correct but much less specific than the evidence supports: Scat is a peripheral subunit of a Golgi tethering complex localized to the trans side of the Golgi. The more specific term Golgi trans cisterna (GO:0000138) is already annotated to scat by IDA (PMID:27481842). DROME/scu GO:0016616 oxidoreductase activity, acting on the CH-OH group of donors, NAD or NADP as acceptor ARBA:ARBA00028442 KEEP_AS_NON_CORE very general (>200 descendants) 364 DROME/sgg GO:0007276 gamete generation ARBA:ARBA00028211 KEEP_AS_NON_CORE general (21-200) 165 DROME/shop GO:0005739 mitochondrion ARBA:ARBA00026962 MODIFY general (21-200) 70 NEEDS_MORE_SPECIFIC true but uninformative replacement term Correct but general. Shopper is a SUOX homolog, and SUOX enzymes reside in the mitochondrial intermembrane space, which is already annotated to shop (TAS). The specific compartment is preferred; applied to all mitochondrion rows. DROME/shop GO:0070013 intracellular organelle lumen ARBA:ARBA00027917 MODIFY very general (>200 descendants) 239 NEEDS_MORE_SPECIFIC true but uninformative replacement term Correct but very general; the specific lumen is the mitochondrial intermembrane space, already annotated. DROME/sima GO:0045944 positive regulation of transcription by RNA polymerase II ARBA:ARBA00027996 ACCEPT specific (1-20) 12 DROME/sns GO:0009653 anatomical structure morphogenesis ARBA:ARBA00026583 KEEP_AS_NON_CORE very general (>200 descendants) 1501 DROME/sns GO:0030154 cell differentiation ARBA:ARBA00027429 KEEP_AS_NON_CORE very general (>200 descendants) 1345 DROME/sns GO:0160108 animal gross anatomical part developmental process ARBA:ARBA00098139 KEEP_AS_NON_CORE very general (>200 descendants) 3010 DROME/so GO:0001654 eye development ARBA:ARBA00027551 ACCEPT general (21-200) 114 DROME/so GO:0009887 animal organ morphogenesis ARBA:ARBA00028067 KEEP_AS_NON_CORE very general (>200 descendants) 585 DROME/so GO:0048646 anatomical structure formation involved in morphogenesis ARBA:ARBA00028539 KEEP_AS_NON_CORE very general (>200 descendants) 488 DROME/sws GO:0016020 membrane ARBA:ARBA00028763 REMOVE very general (>200 descendants) 895 TOO_GENERAL true but uninformative manual TOO_GENERAL Too general. SWS specifically localizes to ER membrane, which is captured by more specific terms with experimental evidence. DROME/tgo GO:0003677 DNA binding ARBA:ARBA00029224 ACCEPT general (21-200) 130 DROME/tgo GO:0045944 positive regulation of transcription by RNA polymerase II ARBA:ARBA00027996 ACCEPT specific (1-20) 12 DROME/tin GO:0006357 regulation of transcription by RNA polymerase II ARBA:ARBA00028137 ACCEPT general (21-200) 56 DROME/tin GO:0007399 nervous system development ARBA:ARBA00027428 REMOVE very general (>200 descendants) 913 WRONG_PARALOG wrong manual WRONG_PARALOG tin is a mesoderm-specific factor; this rule likely reflects neural roles of vertebrate NK-2 paralogs (e.g. Nkx2-1, Nkx2-2). The only nervous-system phenotypes reported for tin (loss of FMRFa Ap4 neuron identity) are non-autonomous, depending on retrograde BMP signals from peripheral targets, and do not indicate that tin acts in neural development. DROME/tin GO:0035050 embryonic heart tube development ARBA:ARBA00089442 ACCEPT specific (1-20) 16 DROME/tin GO:0048565 digestive tract development ARBA:ARBA00091747 MODIFY general (21-200) 56 OTHER_TERM different term needed replacement term tin role in the gut is specification of visceral mesoderm (gut musculature) via bagpipe; visceral muscle development is the accurate term. DROME/tin GO:0055007 cardiac muscle cell differentiation ARBA:ARBA00084649 ACCEPT general (21-200) 29 DROME/toy GO:0009791 post-embryonic development ARBA:ARBA00029007 MARK_AS_OVER_ANNOTATED very general (>200 descendants) 271 TOO_GENERAL true but uninformative uninformative Technically true (eye-antennal disc and ocellus development are post-embryonic) but uninformative; specific terms (eye-antennal disc development, ocellus development, compound eye development) are annotated with experimental evidence. DROME/toy GO:0030154 cell differentiation ARBA:ARBA00027429 MARK_AS_OVER_ANNOTATED very general (>200 descendants) 1345 TOO_GENERAL true but uninformative general Very general term; Toy acts in tissue/organ specification (eye-antennal disc, ocelli, compound eye) rather than in a defined cell differentiation step. Specific developmental terms are already annotated. DROME/toy GO:0045944 positive regulation of transcription by RNA polymerase II ARBA:ARBA00027996 ACCEPT specific (1-20) 12 DROME/toy GO:0048731 system development ARBA:ARBA00027702 MARK_AS_OVER_ANNOTATED very general (>200 descendants) 2438 TOO_GENERAL true but uninformative general Extremely general; adds nothing beyond the specific experimentally supported developmental terms (compound eye, ocellus, eye-antennal disc, brain). DROME/toy GO:0090596 sensory organ morphogenesis ARBA:ARBA00043576 KEEP_AS_NON_CORE general (21-200) 116 DROME/ttv GO:1901135 carbohydrate derivative metabolic process ARBA:ARBA00026297 UNDECIDED very general (>200 descendants) 637 DROME/wrd GO:0005654 nucleoplasm ARBA:ARBA00026290 KEEP_AS_NON_CORE general (21-200) 65 DROME/wry GO:0000902 cell morphogenesis ARBA:ARBA00028811 MARK_AS_OVER_ANNOTATED general (21-200) 157 NO_EVIDENCE overreach no evidence ARBA rules transferred from canonical Notch-pathway proteins; there is no evidence that Wry acts in neural or glial development or cell morphogenesis, and wry deficiencies lack the sensory-organ and wing defects typical of Notch-pathway mutants. DROME/wry GO:0007154 cell communication ARBA:ARBA00028945 MODIFY very general (>200 descendants) 1207 NEEDS_MORE_SPECIFIC true but uninformative replacement term Correct but very general; the specific process is Notch signaling pathway, which Wry already carries (IMP). DROME/wry GO:0023052 signaling ARBA:ARBA00026303 MODIFY very general (>200 descendants) 1141 NEEDS_MORE_SPECIFIC true but uninformative replacement term Correct but very general; the specific process is Notch signaling pathway, which Wry already carries (IMP). DROME/wry GO:0042063 gliogenesis ARBA:ARBA00086246 MARK_AS_OVER_ANNOTATED general (21-200) 83 NO_EVIDENCE overreach no evidence ARBA rules transferred from canonical Notch-pathway proteins; there is no evidence that Wry acts in neural or glial development or cell morphogenesis, and wry deficiencies lack the sensory-organ and wing defects typical of Notch-pathway mutants. DROME/wry GO:0048666 neuron development ARBA:ARBA00028378 MARK_AS_OVER_ANNOTATED general (21-200) 186 NO_EVIDENCE overreach no evidence ARBA rules transferred from canonical Notch-pathway proteins; there is no evidence that Wry acts in neural or glial development or cell morphogenesis, and wry deficiencies lack the sensory-organ and wing defects typical of Notch-pathway mutants. ECOLI/ahpF GO:0005829 cytosol ARBA:ARBA00029243 ACCEPT general (21-200) 73 ECOLI/ahpF GO:0032991 protein-containing complex ARBA:ARBA00028902 MODIFY very general (>200 descendants) 2083 NEEDS_MORE_SPECIFIC true but uninformative replacement term GO:0032991 is true but too general for AhpF. Dip et al. directly demonstrated binding between EcAhpF and EcAhpC and support replacing this generic complex assertion with GO:0009321 alkyl hydroperoxide reductase complex. ECOLI/DnaK GO:0051087 protein-folding chaperone binding ARBA:ARBA00088077 ACCEPT specific (1-20) 1 ECOLI/LepB GO:0008233 peptidase activity ARBA:ARBA00027408 MODIFY general (21-200) 81 NEEDS_MORE_SPECIFIC true but uninformative replacement term The broad peptidase parent adds no useful specificity beyond GO:0009003 signal peptidase activity. ECOLI/SecA GO:0031522 cell envelope Sec protein transport complex ARBA:ARBA00085510 ACCEPT leaf (0) 0 ECOLI/SecA GO:0043952 protein transport by the Sec complex ARBA:ARBA00086631 ACCEPT leaf (0) 0 ECOLI/SlyD GO:0042026 protein refolding ARBA:ARBA00043587 ACCEPT leaf (0) 0 ECOLI/clsC GO:0030572 phosphatidyltransferase activity ARBA:ARBA00043336 MODIFY specific (1-20) 3 NEEDS_MORE_SPECIFIC true but uninformative replacement term The generic ARBA phosphatidyltransferase prediction should be replaced with GO:0090483, because E. coli ClsC has direct biochemical evidence for phosphatidylglycerol-phosphatidylethanolamine phosphatidyltransferase activity. ECOLI/degP GO:0030163 protein catabolic process ARBA:ARBA00027403 ACCEPT general (21-200) 66 ECOLI/degP GO:0042597 periplasmic space ARBA:ARBA00027528 ACCEPT specific (1-20) 4 ECOLI/degP GO:0042802 identical protein binding ARBA:ARBA00027930 KEEP_AS_NON_CORE specific (1-20) 1 ECOLI/dsbA GO:0015036 disulfide oxidoreductase activity ARBA:ARBA00026549 KEEP_AS_NON_CORE specific (1-20) 14 ECOLI/fruK GO:0008443 phosphofructokinase activity ARBA:ARBA00043440 MODIFY specific (1-20) 4 NEEDS_MORE_SPECIFIC true but uninformative replacement term GO:0008662 is the experimentally supported substrate-specific kinase activity. ECOLI/glpD GO:0016020 membrane ARBA:ARBA00028763 MARK_AS_OVER_ANNOTATED very general (>200 descendants) 895 TOO_GENERAL true but uninformative broad The broad membrane IEA should be narrowed to GO:0005886 because E. coli GlpD is a monotopic enzyme associated with the cytoplasmic face of the inner membrane. ECOLI/glpK GO:0005829 cytosol ARBA:ARBA00029243 ACCEPT general (21-200) 73 ECOLI/hldE GO:0016772 transferase activity, transferring phosphorus-containing groups ARBA:ARBA00026261 MARK_AS_OVER_ANNOTATED very general (>200 descendants) 567 TOO_GENERAL true but uninformative more informative The exact kinase and adenylyltransferase terms are more informative and should carry the core assertions. ECOLI/lpd GO:0006979 response to oxidative stress ARBA:ARBA00026273 MARK_AS_OVER_ANNOTATED general (21-200) 42 UNCLASSIFIED unclassified The deletion/codon-usage data indicate stress sensitivity but do not establish that LpdA itself executes a dedicated oxidative-stress response step. ECOLI/rlmC GO:0008757 S-adenosylmethionine-dependent methyltransferase activity ARBA:ARBA00026462 KEEP_AS_NON_CORE very general (>200 descendants) 242 ECOLI/rlmC GO:0009451 RNA modification ARBA:ARBA00028213 KEEP_AS_NON_CORE general (21-200) 118 ECOLI/rnc GO:0042802 identical protein binding ARBA:ARBA00027930 MODIFY specific (1-20) 1 NEEDS_MORE_SPECIFIC true but uninformative replacement term Parent-level ARBA assertion replaced by the specific dimerization term that is experimentally established for this protein. ECOLI/yegV GO:0006796 phosphate-containing compound metabolic process ARBA:ARBA00028024 ACCEPT general (21-200) 44 ECOLI/yegV GO:0016772 transferase activity, transferring phosphorus-containing groups ARBA:ARBA00026261 ACCEPT very general (>200 descendants) 567 ECOLI/ygfF GO:0016614 oxidoreductase activity, acting on CH-OH group of donors ARBA:ARBA00028437 ACCEPT very general (>200 descendants) 457 EMENI/flbD GO:0003006 developmental process involved in reproduction ARBA:ARBA00026397 KEEP_AS_NON_CORE very general (>200 descendants) 482 EMENI/flbD GO:0009653 anatomical structure morphogenesis ARBA:ARBA00026583 KEEP_AS_NON_CORE very general (>200 descendants) 1501 EMENI/flbD GO:0009791 post-embryonic development ARBA:ARBA00029007 MARK_AS_OVER_ANNOTATED very general (>200 descendants) 271 WRONG_TAXON wrong not applicable to ARBA propagation from multicellular animal/plant Myb orthologs; not applicable to fungal conidiation. EMENI/flbD GO:0009888 tissue development MARK_AS_OVER_ANNOTATED very general (>200 descendants) 1023 WRONG_TAXON wrong fungi Filamentous fungi do not form tissues in this sense; ARBA over-propagation. EMENI/flbD GO:0030154 cell differentiation KEEP_AS_NON_CORE very general (>200 descendants) 1345 EMENI/flbD GO:0032875 regulation of DNA endoreduplication ARBA:ARBA00085610 MARK_AS_OVER_ANNOTATED specific (1-20) 2 NO_EVIDENCE overreach No evidence No evidence FlbD regulates endoreduplication in A. nidulans; ARBA over-propagation. EMENI/flbD GO:0033993 response to lipid ARBA:ARBA00028073 MARK_AS_OVER_ANNOTATED general (21-200) 164 NO_EVIDENCE overreach without experimental support ARBA electronic propagation without experimental support in A. nidulans. EMENI/flbD GO:0043565 sequence-specific DNA binding ARBA:ARBA00026779 ACCEPT general (21-200) 60 EMENI/flbD GO:0048582 positive regulation of post-embryonic development ARBA:ARBA00091211 MARK_AS_OVER_ANNOTATED specific (1-20) 11 WRONG_TAXON wrong fungi ARBA propagation from multicellular orthologs; inapplicable to fungi. EMENI/flbD GO:0048731 system development ARBA:ARBA00027702 MARK_AS_OVER_ANNOTATED very general (>200 descendants) 2438 WRONG_TAXON wrong not applicable to ARBA over-propagation; not applicable to a fungus. EMENI/flbD GO:0050891 multicellular organismal-level water homeostasis ARBA:ARBA00091200 REMOVE specific (1-20) 3 WRONG_TAXON wrong manual WRONG_TAXON 'Multicellular organismal-level water homeostasis' is a plant/animal physiology term with no basis in Aspergillus; a clear ARBA mis-propagation. EMENI/flbD GO:0097305 response to alcohol ARBA:ARBA00033534 MARK_AS_OVER_ANNOTATED general (21-200) 69 NO_EVIDENCE overreach without experimental support ARBA electronic propagation without experimental support. EMENI/flbD GO:1901002 positive regulation of response to salt stress ARBA:ARBA00089230 REMOVE leaf (0) 0 WRONG_TAXON wrong manual WRONG_TAXON Propagated from plant Myb stress-response regulators; no basis in A. nidulans FlbD. EMENI/flbD GO:1902584 positive regulation of response to water deprivation ARBA:ARBA00092220 REMOVE leaf (0) 0 WRONG_TAXON wrong manual WRONG_TAXON Propagated from plant Myb drought-response regulators; inapplicable to a fungus. EMENI/flbD GO:1902806 regulation of cell cycle G1/S phase transition ARBA:ARBA00033981 MARK_AS_OVER_ANNOTATED specific (1-20) 9 UNCLASSIFIED unclassified Propagated from mammalian cell-cycle Myb proteins; not FlbD's characterized role. EMENI/flbD GO:2000037 regulation of stomatal complex patterning ARBA:ARBA00087651 REMOVE leaf (0) 0 WRONG_TAXON wrong manual WRONG_TAXON Regulation of stomatal complex patterning applies only to plants; A. nidulans has no stomata. A clear taxon-violating over-propagation. EMENI/flbD GO:0048869 cellular developmental process ARBA:ARBA00026963 KEEP_AS_NON_CORE very general (>200 descendants) 1368 EMENI/nudA GO:0003006 developmental process involved in reproduction ARBA:ARBA00026397 KEEP_AS_NON_CORE very general (>200 descendants) 482 EMENI/nudA GO:0005868 cytoplasmic dynein complex ARBA:ARBA00088183 ACCEPT leaf (0) 0 EMENI/nudA GO:0007097 nuclear migration ARBA:ARBA00026920 ACCEPT specific (1-20) 18 EMENI/nudA GO:0048468 cell development ARBA:ARBA00028665 MARK_AS_OVER_ANNOTATED very general (>200 descendants) 672 INDIRECT_EFFECT overreach phenotype A generic developmental term from an ARBA model; nudA developmental phenotypes (conidiation, metula development) are indirect consequences of failed nuclear distribution and are captured more specifically by the IMP metula development row. EMENI/nudA GO:0048731 system development ARBA:ARBA00027702 REMOVE very general (>200 descendants) 2438 WRONG_TAXON wrong manual WRONG_TAXON System development (progression of an organ system) is a multicellular-animal/plant developmental concept with no counterpart in a filamentous fungus; the ARBA model likely reflects animal dynein heavy chain annotations. The A. nidulans developmental roles are covered by metula development. EMENI/nudA GO:0072384 organelle transport along microtubule ARBA:ARBA00045035 ACCEPT general (21-200) 26 EMENI/nudF GO:0015630 microtubule cytoskeleton ARBA:ARBA00029268 ACCEPT general (21-200) 108 EMENI/wA GO:0046148 pigment biosynthetic process ARBA:ARBA00027688 ACCEPT general (21-200) 52 EMENI/yA GO:0042440 pigment metabolic process ARBA:ARBA00028008 ACCEPT general (21-200) 84 ENTCL/aac6-Ib GO:0046677 response to antibiotic ARBA:ARBA00026946 ACCEPT specific (1-20) 14 GADMO/A0A8C5FPT8 GO:0005773 vacuole ARBA:ARBA00028576 MARK_AS_OVER_ANNOTATED general (21-200) 78 TOO_GENERAL true but uninformative general No evidence from mammalian ortholog studies supports vacuolar localization for TBC1D14. The protein localizes to recycling endosomes and Golgi, not to vacuoles/lysosomes. This ARBA IEA annotation appears to be an over-generalization. GADMO/A0A8C5FPT8 GO:0016192 vesicle-mediated transport ARBA:ARBA00028249 ACCEPT very general (>200 descendants) 232 GADMO/A0A8C5FPT8 GO:0019899 enzyme binding ARBA:ARBA00026481 MARK_AS_OVER_ANNOTATED general (21-200) 77 TOO_GENERAL true but uninformative already captured While TBC1D14 does bind enzymes (RAB11 GTPase, ULK1 kinase), this is already captured more informatively by the small GTPase binding annotation. The generic enzyme binding term adds no biological insight. GADMO/A0A8C5FPT8 GO:0031410 cytoplasmic vesicle ARBA:ARBA00027190 ACCEPT very general (>200 descendants) 274 HETGA/Cd44 GO:0032991 protein-containing complex ARBA:ARBA00028902 MODIFY very general (>200 descendants) 2083 NEEDS_MORE_SPECIFIC true but uninformative replacement term The essence is sound - CD44 does function within multiprotein assemblies - but the root term states nothing. The only specific complex supported anywhere in this annotation set is the macrophage migration inhibitory factor receptor complex, whose GO definition names CD44 explicitly, so that is the term the assertion should resolve to. A caution worth recording: in naked mole-rat tissue the dominant ligand actively opposes CD44 assembly, since very-high-molecular-mass hyaluronan suppresses CD44 protein-protein interactions where ordinary high-mass hyaluronan promotes them. HETGA/Cd44 GO:0048731 system development ARBA:ARBA00027702 MARK_AS_OVER_ANNOTATED very general (>200 descendants) 2438 INDIRECT_EFFECT overreach phenotype The term is so general that it neither informs a reader nor constrains a model: almost any broadly expressed signalling receptor would satisfy it. It rests on a statistical rule rather than on any observation of this protein, and no developmental phenotype has been reported for naked mole-rat CD44. Marked over-annotated rather than removed, since CD44 does participate in development in other mammals and the statement is not false, merely empty. HETGA/Cd44 GO:0160108 animal gross anatomical part developmental process ARBA:ARBA00098139 MARK_AS_OVER_ANNOTATED very general (>200 descendants) 3010 TOO_GENERAL true but uninformative grouping A grouping term of this altitude cannot be wrong and cannot be useful. It is machine assigned, has no naked mole-rat support, and duplicates in substance the system development annotation. If a developmental role for naked mole-rat CD44 is ever established it should be recorded at the level of the actual structure involved. HETGA/Cd44 GO:2000106 regulation of leukocyte apoptotic process ARBA:ARBA00088582 KEEP_AS_NON_CORE general (21-200) 53 HETGA/Ntrk1 GO:0005770 late endosome ARBA:ARBA00028569 MODIFY specific (1-20) 13 NEEDS_MORE_SPECIFIC true but uninformative replacement term "TrkA is an integral membrane protein, so the compartment-level term ""late endosome"" is less accurate than the membrane-level term. UniProt's own subcellular location statement is specifically ""Late endosome membrane; Single-pass type I membrane protein"", and GO:0031902 late endosome membrane is already present in this GOA set from the SubCell mapping. There is no naked-mole-rat evidence bearing on endosomal residence either way; this is a conserved-trafficking transfer from the well-characterised human and rat receptor." HETGA/Ntrk1 GO:0031175 neuron projection development ARBA:ARBA00026765 MODIFY general (21-200) 124 NEEDS_MORE_SPECIFIC true but uninformative replacement term The ARBA transfer captures a real function, but TrkA acts upstream, converting an extracellular NGF signal into increased neurite elaboration; it is not itself part of the machinery that builds the projection. The regulatory child GO:0010976 is both more accurate and directly evidenced in this species by the demonstration that NGF drives extensive neurite outgrowth in TrkA-positive naked mole-rat sensory neurons. HETGA/Ntrk1 GO:0043524 negative regulation of neuron apoptotic process ARBA:ARBA00085502 ACCEPT specific (1-20) 6 HORSE/ALDH7A1 GO:0019477 L-lysine catabolic process ARBA:ARBA00084340 UNDECIDED specific (1-20) 1 HORSE/BCAT2 GO:0009083 branched-chain amino acid catabolic process ARBA:ARBA00091432 ACCEPT specific (1-20) 4 HORSE/CXCR3 GO:0009986 cell surface ARBA:ARBA00027349 ACCEPT specific (1-20) 14 HORSE/GEMIN5 GO:0003730 mRNA 3'-UTR binding ARBA:ARBA00028422 UNDECIDED specific (1-20) 1 HORSE/GHSR GO:0007154 cell communication ARBA:ARBA00028945 KEEP_AS_NON_CORE very general (>200 descendants) 1207 HORSE/GHSR GO:0023052 signaling ARBA:ARBA00026303 KEEP_AS_NON_CORE very general (>200 descendants) 1141 HORSE/GHSR GO:0038023 signaling receptor activity ARBA:ARBA00027254 MODIFY very general (>200 descendants) 389 NEEDS_MORE_SPECIFIC true but uninformative replacement term GHSR is a peptide-hormone-binding GPCR, but the specific ghrelin/growth-hormone-secretagogue receptor activity is more informative than generic receptor or peptide-binding terms. HORSE/HSPD1 GO:0005832 chaperonin-containing T-complex ARBA:ARBA00029273 REMOVE leaf (0) 0 WRONG_PARALOG wrong manual WRONG_PARALOG The selected sequence belongs to the Cpn60/GroEL branch and retains a mitochondrial precursor segment. Human structural/biochemical work establishes the Hsp60/Hsp10 type I system. The internal deletion does not turn it into a CCT paralog. The ARBA assertion and ProtNLM narrative agree on an incorrect complex identity; their agreement is not biological validation. HORSE/KRIT1 GO:0051093 negative regulation of developmental process ARBA:ARBA00027583 KEEP_AS_NON_CORE very general (>200 descendants) 504 HORSE/KRIT1 GO:2000026 regulation of multicellular organismal development ARBA:ARBA00026275 KEEP_AS_NON_CORE very general (>200 descendants) 464 HORSE/MAP2K2 GO:0005739 mitochondrion ARBA:ARBA00026962 UNDECIDED general (21-200) 70 HORSE/MAP2K2 GO:0005769 early endosome ARBA:ARBA00028567 UNDECIDED specific (1-20) 7 HORSE/MAP2K2 GO:0005770 late endosome ARBA:ARBA00028569 UNDECIDED specific (1-20) 13 HORSE/MAP2K2 GO:0005925 focal adhesion ARBA:ARBA00028361 UNDECIDED leaf (0) 0 HORSE/MAP2K2 GO:0032872 regulation of stress-activated MAPK cascade ARBA:ARBA00026638 UNDECIDED specific (1-20) 5 HORSE/MAP2K2 GO:0090170 regulation of Golgi inheritance ARBA:ARBA00028400 UNDECIDED leaf (0) 0 HORSE/MAP2K2 GO:2000641 regulation of early endosome to late endosome transport ARBA:ARBA00028332 UNDECIDED specific (1-20) 2 HORSE/MTMR9 GO:0005829 cytosol ARBA:ARBA00029243 ACCEPT general (21-200) 73 HORSE/MTMR9 GO:0030234 enzyme regulator activity ARBA:ARBA00026580 ACCEPT general (21-200) 170 HORSE/PEA15 GO:1902042 negative regulation of extrinsic apoptotic signaling pathway via death domain receptors ARBA:ARBA00088654 ACCEPT specific (1-20) 1 HORSE/USP8 GO:0005829 cytosol ARBA:ARBA00029243 ACCEPT general (21-200) 73 HORSE/USP8 GO:0030496 midbody ARBA:ARBA00033509 KEEP_AS_NON_CORE specific (1-20) 1 JUGRE/A0A2I4G8T1 GO:0016757 glycosyltransferase activity ARBA:ARBA00026308 MARK_AS_OVER_ANNOTATED very general (>200 descendants) 434 TOO_GENERAL true but uninformative broad This is the broadest of the three molecular function annotations and adds no information beyond what is captured by the more specific terms. The protein's domain architecture and phylogenetic placement clearly place it in the UDP-glycosyltransferase family, making this overly general annotation uninformative. MEDTR/NFP GO:0051707 response to other organism ARBA:ARBA00029118 MODIFY general (21-200) 199 NEEDS_MORE_SPECIFIC true but uninformative replacement term """Response to other organism"" is accurate but uninformatively general. The specific, experimentally documented responses are already, or should be, represented by more precise terms: response to molecule of bacterial origin (GO:0002237, existing IMP), nodulation (GO:0009877), and the defense-response regulation terms. The best single specific replacement that captures NFP's defining symbiotic role is ""response to molecule of bacterial origin"" (GO:0002237), already present from PMID:12753588." MEDTR/NSP1 GO:0009610 response to symbiotic fungus ARBA:ARBA00026468 KEEP_AS_NON_CORE specific (1-20) 1 METBS/Mlac1 GO:0003824 catalytic activity ARBA:ARBA00027533 MODIFY very general (>200 descendants) 6405 NEEDS_MORE_SPECIFIC true but uninformative replacement term Too general. The specific catalytic activity is laccase activity (EC 1.10.3.-), which is an oxidoreductase that oxidizes phenolic substrates. METEA/mllA GO:0016881 acid-amino acid ligase activity ARBA:ARBA00028624 ACCEPT general (21-200) 54 METEA/mllBC GO:0016881 acid-amino acid ligase activity ARBA:ARBA00028624 ACCEPT general (21-200) 54 METEA/mxaF GO:0003824 catalytic activity ARBA:ARBA00027533 KEEP_AS_NON_CORE very general (>200 descendants) 6405 METEA/mxaF GO:0070968 pyrroloquinoline quinone binding ARBA:ARBA00086199 ACCEPT leaf (0) 0 METEA/mxcQ GO:0004672 protein kinase activity ARBA:ARBA00027018 KEEP_AS_NON_CORE general (21-200) 115 METEA/serA GO:0006564 L-serine biosynthetic process ARBA:ARBA00093701 ACCEPT leaf (0) 0 METEA/xoxF1 GO:0003824 catalytic activity ARBA:ARBA00027533 MARK_AS_OVER_ANNOTATED very general (>200 descendants) 6405 TOO_GENERAL true but uninformative uninformative Correct but uninformative parent term. XoxF1 is an enzyme with well-characterized catalytic activity for methanol oxidation. This is a general root-level term subsumed by the more specific molecular function annotations (GO:0016614, GO:0052933) that should be retained as the core function. METEA/xoxF1 GO:0070968 pyrroloquinoline quinone binding ARBA:ARBA00086199 ACCEPT leaf (0) 0 MISSI/CAD GO:0009809 lignin biosynthetic process ARBA:ARBA00034952 ACCEPT specific (1-20) 3 MISSI/CDT1 GO:0010038 response to metal ion ARBA:ARBA00028342 KEEP_AS_NON_CORE general (21-200) 64 MISSI/MnSOD GO:0006950 response to stress ARBA:ARBA00026300 KEEP_AS_NON_CORE very general (>200 descendants) 590 MISSI/ramosa1 GO:0006355 regulation of DNA-templated transcription ARBA:ARBA00028138 ACCEPT general (21-200) 140 MONBE/MONBRDRAFT_1233 GO:0071944 cell periphery ARBA:ARBA00027443 UNDECIDED very general (>200 descendants) 493 MYCTU/cds1 GO:1901605 alpha-amino acid metabolic process ARBA:ARBA00026968 ACCEPT leaf (0) 0 NEMVE/G9JWI5 GO:0003008 system process ARBA:ARBA00026405 REMOVE very general (>200 descendants) 471 UNSUPPORTED overreach manual UNSUPPORTED """System process"" refers to physiological processes carried out by organ systems. There is no evidence that NvNotch acts in such a process in Nematostella; the ARBA rule transfers a generic bilaterian vertebrate-derived term. NvNotch's roles are developmental signalling roles." NEMVE/G9JWI5 GO:0007166 cell surface receptor signaling pathway ARBA:ARBA00029053 KEEP_AS_NON_CORE very general (>200 descendants) 403 NEMVE/G9JWI5 GO:0007399 nervous system development ARBA:ARBA00027428 KEEP_AS_NON_CORE very general (>200 descendants) 913 NEMVE/G9JWI5 GO:0009952 anterior/posterior pattern specification ARBA:ARBA00027259 MARK_AS_OVER_ANNOTATED general (21-200) 74 NO_EVIDENCE overreach not supported Nematostella has an oral-aboral axis rather than a bilaterian anterior/posterior axis; Notch signalling is needed for axis re-establishment in gastruloids, but this is via germ-layer self-organisation and has only inhibitor/Su(H) evidence. The A/P specification term is not supported as a direct NvNotch function. NEMVE/G9JWI5 GO:0019904 protein domain specific binding ARBA:ARBA00087321 REMOVE general (21-200) 79 TOO_GENERAL true but uninformative manual TOO_GENERAL Generic binding term that conveys no functional information and has no Nematostella-specific evidence; the informative function is captured by transmembrane signaling receptor activity. Removal does not deny that NvNotch domains mediate protein interactions. NEMVE/G9JWI5 GO:0030097 hemopoiesis ARBA:ARBA00028409 REMOVE general (21-200) 161 WRONG_TAXON wrong manual WRONG_TAXON Cnidarians have no hematopoietic system; the term is a taxonomically inappropriate transfer from vertebrate Notch biology. NEMVE/G9JWI5 GO:0035282 segmentation ARBA:ARBA00091150 REMOVE general (21-200) 78 WRONG_TAXON wrong manual WRONG_TAXON Nematostella is not segmented; the term is a taxonomically inappropriate transfer from vertebrate somitogenesis/arthropod segmentation. NEMVE/G9JWI5 GO:0048646 anatomical structure formation involved in morphogenesis ARBA:ARBA00028539 KEEP_AS_NON_CORE very general (>200 descendants) 488 NEMVE/G9JWI5 GO:0048863 stem cell differentiation ARBA:ARBA00090702 MARK_AS_OVER_ANNOTATED general (21-200) 37 UNCLASSIFIED unclassified Notch signalling likely regulates differentiation from progenitor pools (e.g. cnidocyte progenitors), but there is no direct stem-cell evidence for NvNotch; the term is a vertebrate-derived over-annotation. NEMVE/G9JWI5 GO:0051240 positive regulation of multicellular organismal process ARBA:ARBA00028891 MARK_AS_OVER_ANNOTATED very general (>200 descendants) 565 TOO_GENERAL true but uninformative Uninformative Uninformative high-level regulatory term; in Nematostella NvNotch mainly acts to restrain differentiation, and the direction-specific claim is not supported. NEMVE/G9JWI6 GO:0007399 nervous system development ARBA:ARBA00027428 KEEP_AS_NON_CORE very general (>200 descendants) 913 NEMVE/G9JWI6 GO:0030154 cell differentiation ARBA:ARBA00027429 KEEP_AS_NON_CORE very general (>200 descendants) 1345 NEUCR/NCU01540 GO:0022857 transmembrane transporter activity ARBA:ARBA00028127 MODIFY very general (>200 descendants) 990 NEEDS_MORE_SPECIFIC true but uninformative replacement term The supported Pho91 subfamily and characterized fungal phosphate transport justify phosphate transmembrane transporter activity rather than an unspecified solute. NEUCR/NCU04302 GO:0005694 chromosome ARBA:ARBA00026361 UNDECIDED very general (>200 descendants) 204 NEUCR/NCU04302 GO:0019789 SUMO transferase activity ARBA:ARBA00027358 ACCEPT specific (1-20) 3 NEUCR/NCU04637 GO:0030479 actin cortical patch ARBA:ARBA00028110 ACCEPT specific (1-20) 1 NEUCR/NCU08595 GO:0042254 ribosome biogenesis ARBA:ARBA00026817 MODIFY general (21-200) 78 NEEDS_MORE_SPECIFIC true but uninformative replacement term The broad ribosome-biogenesis or RNA-processing assertion is supported but can be made precise: Rpf2 supports large-subunit rRNA maturation through recruitment and assembly of the 5S ribonucleoprotein particle. NEUCR/NCU09721 GO:0005737 cytoplasm ARBA:ARBA00026971 ACCEPT very general (>200 descendants) 1146 NEUCR/NCU09880 GO:0032991 protein-containing complex ARBA:ARBA00028902 MODIFY very general (>200 descendants) 2083 NEEDS_MORE_SPECIFIC true but uninformative replacement term Protein-containing complex is correct but uninformative for a canonical SmG subunit. Its supported role is in spliceosomal snRNPs and spliceosome complexes. NEUCR/al-1 GO:0008299 isoprenoid biosynthetic process ARBA:ARBA00027662 KEEP_AS_NON_CORE general (21-200) 95 NEUCR/al-1 GO:0016166 phytoene dehydrogenase activity ARBA:ARBA00028168 ACCEPT leaf (0) 0 NEUCR/hsp98 GO:0006457 protein folding ARBA:ARBA00027200 MODIFY specific (1-20) 7 NEEDS_MORE_SPECIFIC true but uninformative replacement term Hsp104/ClpB proteins do not generally fold nascent proteins; they disaggregate damaged proteins so they can be refolded. The fungal PAINT node already asserts GO:0042026 protein refolding for hsp98. NEUCR/hsp98 GO:0034605 cellular response to heat ARBA:ARBA00026567 ACCEPT specific (1-20) 3 NEUCR/hsp98 GO:0043335 protein unfolding ARBA:ARBA00086271 ACCEPT leaf (0) 0 NEUCR/kal-1 GO:0000977 RNA polymerase II transcription regulatory region sequence-specific DNA binding ARBA:ARBA00028973 ACCEPT specific (1-20) 15 NEUCR/lys-4 GO:0005737 cytoplasm ARBA:ARBA00026971 ACCEPT very general (>200 descendants) 1146 NEUCR/mek-1 GO:0000165 MAPK cascade ARBA:ARBA00029221 ACCEPT specific (1-20) 18 NICAT/NaBGL1_candidate_BGLU42 GO:0009821 alkaloid biosynthetic process ARBA:ARBA00028022 REMOVE general (21-200) 34 WRONG_PARALOG wrong manual WRONG_PARALOG The current mapping work indicates that BGLU42 is not the best orthology anchor to the specialized beta-GD pathway enzymes. NICAT/NaMPO1_candidate_AMO_3 GO:0052597 diamine oxidase activity ARBA:ARBA00089312 MODIFY specific (1-20) 2 OTHER_TERM different term needed replacement term GO:0008131 more closely matches the curated MPO1 reaction and avoids keeping two near-duplicate family-level activity labels. NICAT/NaPMT1.1 GO:0009753 response to jasmonic acid ARBA:ARBA00028898 KEEP_AS_NON_CORE specific (1-20) 6 NICAT/NaPMT1.2 GO:0009753 response to jasmonic acid ARBA:ARBA00028898 KEEP_AS_NON_CORE specific (1-20) 6 NICAT/NaPMT3 GO:0009753 response to jasmonic acid ARBA:ARBA00028898 KEEP_AS_NON_CORE specific (1-20) 6 NICAT/NaQPT2_candidate_QPT_0 GO:0009611 response to wounding ARBA:ARBA00026469 KEEP_AS_NON_CORE general (21-200) 40 NICAT/NaQPT2_candidate_QPT_1 GO:0009611 response to wounding ARBA:ARBA00026469 KEEP_AS_NON_CORE general (21-200) 40 NICAT/NaUGT1_candidate_UGT85A2_0 GO:0035251 UDP-glucosyltransferase activity ARBA:ARBA00029194 MODIFY general (21-200) 78 NEEDS_MORE_SPECIFIC true but uninformative replacement term GO:0050139 already exists for this exact reaction. The Cell 2026 NaUGT1 assay/perturbation primers map to the g26396 locus, and its primer-compatible extended ORF contains the complete A0A2H4GSI3 sequence. Independent tobacco UGT1 supplements explicitly map the assayed N-glucosyltransferase to a close homolog (466 identities across 485 alignment columns). This establishes gene-level function; the retrieved assays do not directly test the isolated 485-aa database form. Narrow the generic MF using the existing term rather than proposing a duplicate ontology term. ORYSJ/CPS4 GO:0006721 terpenoid metabolic process ARBA:ARBA00027870 MODIFY general (21-200) 144 NEEDS_MORE_SPECIFIC true but uninformative replacement term "The essence is correct - OsCPS4 is a terpenoid-metabolizing enzyme - but ""terpenoid metabolic process"" is over-general. OsCPS4 specifically performs a biosynthetic cyclization of a diterpenoid (C20) precursor, GGPP, to syn-CPP, the committed step toward the syn-labdane diterpenoids momilactones and oryzalexin S [PMID:15255861, PMID:15341631]. The more accurate and specific term is ""diterpenoid biosynthetic process"" (GO:0016102), which conveys both the C20/diterpenoid class and the biosynthetic direction. Recommend modifying to GO:0016102." ORYSJ/EIL2 GO:0010104 regulation of ethylene-activated signaling pathway ARBA:ARBA00027580 ACCEPT specific (1-20) 1 ORYSJ/EIL2 GO:0043565 sequence-specific DNA binding ARBA:ARBA00026779 ACCEPT general (21-200) 60 ORYSJ/EIL2 GO:0045893 positive regulation of DNA-templated transcription ARBA:ARBA00029082 ACCEPT general (21-200) 42 ORYSJ/HD3A GO:0009909 regulation of flower development ARBA:ARBA00043323 ACCEPT specific (1-20) 2 ORYSJ/HD3A GO:0010229 inflorescence development ARBA:ARBA00090608 KEEP_AS_NON_CORE specific (1-20) 4 ORYSJ/HD3A GO:0048510 regulation of timing of transition from vegetative to reproductive phase ARBA:ARBA00091784 ACCEPT leaf (0) 0 ORYSJ/HD3A GO:0048573 photoperiodism, flowering ARBA:ARBA00091187 ACCEPT specific (1-20) 2 ORYSJ/MADS3 GO:0009791 post-embryonic development ARBA:ARBA00029007 MARK_AS_OVER_ANNOTATED very general (>200 descendants) 271 TOO_GENERAL true but uninformative generic """Post-embryonic development"" is an extremely generic, ML-derived process term that conveys almost no functional information. OsMADS3's actual developmental role is precisely defined: specification of stamen identity and floral organ identity, plus contribution to floral meristem determinacy. The specific floral terms (GO:0010097 specification of stamen identity, TAS; and GO:0048437 floral organ development, proposed below) fully capture the biology. The broad ARBA term is an over-annotation that adds nothing once the specific floral-development terms are present." ORYSJ/MADS3 GO:0048608 reproductive structure development ARBA:ARBA00028277 MODIFY very general (>200 descendants) 238 NEEDS_MORE_SPECIFIC true but uninformative replacement term "The essence is sound - OsMADS3 is a C-class floral homeotic gene that specifies reproductive (inner-whorl) organ identity - but ""reproductive structure development"" is a broad grouping term. The gene's documented role is more precisely the development and identity specification of floral organs (especially stamens). MODIFY to the more specific ""floral organ development"" (GO:0048437), which is accurate, non-obsolete, and complements the retained specific term GO:0010097 (specification of stamen identity)." ORYSJ/MET1A GO:0045814 negative regulation of gene expression, epigenetic ARBA:ARBA00033599 KEEP_AS_NON_CORE general (21-200) 27 OSCPE/TLN GO:0070161 anchoring junction ARBA:ARBA00027154 ACCEPT general (21-200) 44 PANAN/crtB GO:0016117 carotenoid biosynthetic process ARBA:ARBA00028033 ACCEPT specific (1-20) 14 PANAN/crtI GO:0016120 carotene biosynthetic process ARBA:ARBA00028053 ACCEPT specific (1-20) 7 PANAN/crtI GO:0016627 oxidoreductase activity, acting on the CH-CH group of donors ARBA:ARBA00028473 ACCEPT general (21-200) 168 PANAN/crtI GO:0071949 FAD binding ARBA:ARBA00084586 ACCEPT leaf (0) 0 PANPA/A0A2R9CAF4 GO:0015698 inorganic anion transport ARBA:ARBA00027809 KEEP_AS_NON_CORE general (21-200) 106 PANTR/TAS2R38 GO:0005886 plasma membrane ARBA:ARBA00027801 ACCEPT very general (>200 descendants) 415 PENCH/aatA GO:0042318 penicillin biosynthetic process ARBA:ARBA00087383 ACCEPT specific (1-20) 1 PENEN/patI GO:0043386 mycotoxin biosynthetic process KEEP_AS_NON_CORE general (21-200) 21 PENEN/patI GO:0044550 secondary metabolite biosynthetic process ARBA:ARBA00029064 KEEP_AS_NON_CORE general (21-200) 164 PHYPA/MPK4a GO:0002221 pattern recognition receptor signaling pathway ARBA:ARBA00033911 ACCEPT general (21-200) 47 POPTR/ACCC1 GO:0016421 CoA carboxylase activity ARBA:ARBA00028582 MODIFY specific (1-20) 4 NEEDS_MORE_SPECIFIC true but uninformative replacement term This protein is the biotin carboxylase (BC) subunit of the heteromeric plastid acetyl-CoA carboxylase; it contributes_to the overall acetyl-CoA carboxylase activity (GO:0003989), while its own direct subunit activity is biotin carboxylase activity (GO:0004075). Falcon deep research confirms that the heteromeric plastid ACCase minimally contains BC, BCCP and CT (alpha-CT and beta-CT) catalytic components, with BC performing the biotin-carboxylation half-reaction. POPTR/ACCC2 GO:0016421 CoA carboxylase activity ARBA:ARBA00028582 MODIFY specific (1-20) 4 NEEDS_MORE_SPECIFIC true but uninformative replacement term This protein is the biotin carboxylase component of acetyl-CoA carboxylase; it contributes to the complex activity while its direct subunit activity is GO:0004075. POPTR/ADLE GO:0016854 racemase and epimerase activity ARBA:ARBA00026938 KEEP_AS_NON_CORE general (21-200) 62 POPTR/MAOX GO:0006108 malate metabolic process ARBA:ARBA00026488 ACCEPT specific (1-20) 1 POPTR/PAL GO:0009611 response to wounding ARBA:ARBA00026469 KEEP_AS_NON_CORE general (21-200) 40 POPTR/PAL GO:0046395 carboxylic acid catabolic process ARBA:ARBA00027882 MODIFY general (21-200) 174 NEEDS_MORE_SPECIFIC true but uninformative replacement term The substrate-specific L-phenylalanine catabolic process (already accepted) is the appropriate term; the generic carboxylic acid catabolic grouping adds no information. POPTR/PCBER GO:0009807 lignan biosynthetic process ARBA:ARBA00027900 ACCEPT specific (1-20) 8 POPTR/RBL901 GO:0032875 regulation of DNA endoreduplication ARBA:ARBA00085610 KEEP_AS_NON_CORE specific (1-20) 2 POPTR/WIN6.2B GO:0050832 defense response to fungus ARBA:ARBA00029244 ACCEPT specific (1-20) 6 POPTR/WIN6.2C GO:0098542 defense response to other organism ARBA:ARBA00027395 ACCEPT general (21-200) 77 POPTR/WIN6 GO:0050832 defense response to fungus ARBA:ARBA00029244 ACCEPT specific (1-20) 6 POPTR/atpA GO:0009536 plastid ARBA:ARBA00027316 MODIFY general (21-200) 124 NEEDS_MORE_SPECIFIC true but uninformative replacement term Use the specific chloroplast thylakoid membrane location. POPTR/atpB GO:0009536 plastid ARBA:ARBA00027316 MODIFY general (21-200) 124 NEEDS_MORE_SPECIFIC true but uninformative replacement term Use the specific thylakoid membrane localization supported by the reviewed entry. POPTR/atpH GO:0009536 plastid ARBA:ARBA00027316 MODIFY general (21-200) 124 NEEDS_MORE_SPECIFIC true but uninformative replacement term Use the more specific chloroplast thylakoid membrane location. POPTR/clpP GO:0009534 chloroplast thylakoid ARBA:ARBA00027312 MODIFY specific (1-20) 15 OTHER_TERM different term needed replacement term UniProt places chloroplast ClpP in the stroma. POPTR/clpP GO:0009840 chloroplastic endopeptidase Clp complex ARBA:ARBA00084875 ACCEPT leaf (0) 0 POPTR/matK GO:0005737 cytoplasm ARBA:ARBA00026971 MODIFY very general (>200 descendants) 1146 NEEDS_MORE_SPECIFIC true but uninformative replacement term The reviewed entry places MatK in the plastid/chloroplast. POPTR/ndhE GO:0009536 plastid ARBA:ARBA00027316 MODIFY general (21-200) 124 NEEDS_MORE_SPECIFIC true but uninformative replacement term Use the specific thylakoid membrane location supported by UniProt. POPTR/ndhK GO:0009536 plastid ARBA:ARBA00027316 MODIFY general (21-200) 124 NEEDS_MORE_SPECIFIC true but uninformative replacement term Use the more specific chloroplast thylakoid membrane term. POPTR/psaJ GO:0009536 plastid ARBA:ARBA00027316 MODIFY general (21-200) 124 NEEDS_MORE_SPECIFIC true but uninformative replacement term Use the more specific chloroplast thylakoid membrane location. POPTR/psbC GO:0009536 plastid ARBA:ARBA00027316 MODIFY general (21-200) 124 NEEDS_MORE_SPECIFIC true but uninformative replacement term Use the specific chloroplast thylakoid membrane location. POPTR/psbD GO:0005737 cytoplasm ARBA:ARBA00026971 MODIFY very general (>200 descendants) 1146 NEEDS_MORE_SPECIFIC true but uninformative replacement term The reviewed entry places PsbD in the chloroplast thylakoid membrane. POPTR/psbI GO:0005737 cytoplasm ARBA:ARBA00026971 MODIFY very general (>200 descendants) 1146 NEEDS_MORE_SPECIFIC true but uninformative replacement term Use the specific chloroplast thylakoid membrane location supported by UniProt. POPTR/psbL GO:0005737 cytoplasm ARBA:ARBA00026971 MODIFY very general (>200 descendants) 1146 NEEDS_MORE_SPECIFIC true but uninformative replacement term Use the specific chloroplast thylakoid membrane location supported by UniProt. POPTR/psbM GO:0005737 cytoplasm ARBA:ARBA00026971 MODIFY very general (>200 descendants) 1146 NEEDS_MORE_SPECIFIC true but uninformative replacement term Use the specific chloroplast thylakoid membrane location supported by UniProt. POPTR/rpl33 GO:0005737 cytoplasm ARBA:ARBA00026971 MODIFY very general (>200 descendants) 1146 NEEDS_MORE_SPECIFIC true but uninformative replacement term Use the chloroplast location supported by UniProt. POPTR/rpl36 GO:0005737 cytoplasm ARBA:ARBA00026971 MODIFY very general (>200 descendants) 1146 NEEDS_MORE_SPECIFIC true but uninformative replacement term Use the chloroplast location supported by UniProt. POPTR/rpoA GO:0005737 cytoplasm ARBA:ARBA00026971 MODIFY very general (>200 descendants) 1146 NEEDS_MORE_SPECIFIC true but uninformative replacement term Use chloroplast localization from the reviewed entry. POPTR/rps15 GO:0005737 cytoplasm ARBA:ARBA00026971 MODIFY very general (>200 descendants) 1146 NEEDS_MORE_SPECIFIC true but uninformative replacement term The reviewed UniProt entry places rps15 in the chloroplast. POPTR/rps19-1 GO:0005737 cytoplasm ARBA:ARBA00026971 MODIFY very general (>200 descendants) 1146 NEEDS_MORE_SPECIFIC true but uninformative replacement term The reviewed UniProt entry places rps19 in the chloroplast, not the cytoplasm. POPTR/rps8 GO:0009536 plastid ARBA:ARBA00027316 MODIFY general (21-200) 124 NEEDS_MORE_SPECIFIC true but uninformative replacement term Use the chloroplast location supported by UniProt. PSEAE/aprA GO:0008233 peptidase activity ARBA:ARBA00027408 ACCEPT general (21-200) 81 PSEAE/ubiE GO:0042181 ketone biosynthetic process ARBA:ARBA00027493 MARK_AS_OVER_ANNOTATED general (21-200) 67 TOO_GENERAL true but uninformative uninformative Technically not wrong (quinones contain ketone-like carbonyl groups), but this is an uninformative high-level grouping term that obscures the actual biology. The specific quinone biosynthesis terms already capture the biology precisely. PSEAI/merA GO:0006979 response to oxidative stress ARBA:ARBA00026273 REMOVE general (21-200) 42 WRONG_PROCESS wrong manual WRONG_PROCESS MerA is specifically induced by mercury via MerR, not by oxidative stress signals PSEPK/BenR GO:0009893 positive regulation of metabolic process ARBA:ARBA00028097 KEEP_AS_NON_CORE very general (>200 descendants) 739 PSEPK/PP_0094 GO:0016791 phosphatase activity ARBA:ARBA00026393 MARK_AS_OVER_ANNOTATED general (21-200) 170 TOO_GENERAL true but uninformative more specific The conserved HAD active site supports phosphohydrolase chemistry, while the PGP-like cap and orthology evidence support a more specific substrate call. PSEPK/PP_0416 GO:0016791 phosphatase activity ARBA:ARBA00026393 MARK_AS_OVER_ANNOTATED general (21-200) 170 TOO_GENERAL true but uninformative captures the GO:0008967 captures the specific substrate and reaction; the generic phosphatase parent should not be treated as the primary function. PSEPK/PP_0581 GO:0016491 oxidoreductase activity ARBA:ARBA00028747 MARK_AS_OVER_ANNOTATED very general (>200 descendants) 1810 TOO_GENERAL true but uninformative captures the UniProt's submitted name and PANTHER subfamily both assign an NADH-dependent 3-oxoacyl reductase; the closer mechanistic annotation below captures the supported reaction class without asserting an experimentally unresolved ACP-versus-CoA substrate. PSEPK/PP_0860 GO:0016655 oxidoreductase activity, acting on NAD(P)H, quinone or similar compound as acceptor ARBA:ARBA00027020 UNDECIDED specific (1-20) 10 PSEPK/PP_0892 GO:0030572 phosphatidyltransferase activity ARBA:ARBA00043336 ACCEPT specific (1-20) 3 PSEPK/PP_1084 GO:0004601 peroxidase activity ARBA:ARBA00028381 ACCEPT general (21-200) 24 PSEPK/PP_1084 GO:0005737 cytoplasm ARBA:ARBA00026971 ACCEPT very general (>200 descendants) 1146 PSEPK/PP_1451 GO:0000270 peptidoglycan metabolic process ARBA:ARBA00028428 ACCEPT specific (1-20) 4 PSEPK/PP_1451 GO:0004180 carboxypeptidase activity ARBA:ARBA00028164 KEEP_AS_NON_CORE specific (1-20) 10 PSEPK/PP_1907 GO:0003824 catalytic activity ARBA:ARBA00027533 MARK_AS_OVER_ANNOTATED very general (>200 descendants) 6405 TOO_GENERAL true but uninformative more specific UniProt identifies PP_1907 as a HAD-like hydrolase, and the OpenScientist report supports a Mg(2+)-dependent phosphatase mechanism with a more specific phosphoglycolate phosphatase prediction. PSEPK/PP_2213 GO:0016405 CoA-ligase activity ARBA:ARBA00028620 KEEP_AS_NON_CORE general (21-200) 47 PSEPK/PP_2320 GO:0000270 peptidoglycan metabolic process ARBA:ARBA00028428 ACCEPT specific (1-20) 4 PSEPK/PP_2320 GO:0004180 carboxypeptidase activity ARBA:ARBA00028164 REMOVE specific (1-20) 10 WRONG_ACTIVITY wrong manual WRONG_ACTIVITY The closely matched ErfK/LdtPae2 subfamily resolves the YkuD reaction as lipoprotein-acceptor L,D-transpeptidation. PSEPK/PP_2483 GO:0016779 nucleotidyltransferase activity ARBA:ARBA00026258 ACCEPT general (21-200) 106 PSEPK/PP_2589 GO:0016620 oxidoreductase activity, acting on the aldehyde or oxo group of donors, NAD or NADP as acceptor ARBA:ARBA00028482 MODIFY general (21-200) 80 NEEDS_MORE_SPECIFIC true but uninformative replacement term Replace this broad class term with GO:0004030 without asserting a specific physiological aldehyde substrate. PSEPK/PP_3157 GO:0016791 phosphatase activity ARBA:ARBA00026393 MARK_AS_OVER_ANNOTATED general (21-200) 170 TOO_GENERAL true but uninformative adds no GO:0016791 adds no useful information beyond the specific histidinol-phosphatase activity already assigned. PSEPK/PP_3195 GO:0052689 carboxylic ester hydrolase activity ARBA:ARBA00028109 ACCEPT general (21-200) 122 PSEPK/PP_3199 GO:0016709 oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, NAD(P)H as one donor, and incorporation of one atom of oxygen ARBA:ARBA00027634 ACCEPT general (21-200) 110 PSEPK/PP_3443 GO:0016620 oxidoreductase activity, acting on the aldehyde or oxo group of donors, NAD or NADP as acceptor ARBA:ARBA00028482 KEEP_AS_NON_CORE general (21-200) 80 PSEPK/PP_3768 GO:0016491 oxidoreductase activity ARBA:ARBA00028747 MARK_AS_OVER_ANNOTATED very general (>200 descendants) 1810 TOO_GENERAL true but uninformative more informative The specific shikimate dehydrogenase activity annotation is more informative; the generic oxidoreductase parent adds little. PSEPK/PP_4230 GO:0016779 nucleotidyltransferase activity ARBA:ARBA00026258 ACCEPT general (21-200) 106 PSEPK/PP_5276 GO:0030572 phosphatidyltransferase activity ARBA:ARBA00043336 ACCEPT specific (1-20) 3 PSEPK/accC GO:0003824 catalytic activity ARBA:ARBA00027533 MARK_AS_OVER_ANNOTATED very general (>200 descendants) 6405 UNCLASSIFIED unclassified UniProt records the ATP-dependent biotin-carboxylation half-reaction. PSEPK/aceA GO:0006097 glyoxylate cycle ARBA:ARBA00084698 ACCEPT leaf (0) 0 PSEPK/acnA-II GO:0016836 hydro-lyase activity ARBA:ARBA00026984 ACCEPT general (21-200) 120 PSEPK/acnB GO:0003730 mRNA 3'-UTR binding ARBA:ARBA00028422 MARK_AS_OVER_ANNOTATED specific (1-20) 1 UNCLASSIFIED unclassified This electronic ARBA prediction transfers an apo-aconitase moonlighting function demonstrated in other bacteria. No transcript-binding or post-transcriptional-regulation evidence was found for Q88KF1 in P. putida, so the term should not be treated as established for this target. PSEPK/adhP GO:0016616 oxidoreductase activity, acting on the CH-OH group of donors, NAD or NADP as acceptor ARBA:ARBA00028442 KEEP_AS_NON_CORE very general (>200 descendants) 364 PSEPK/aldB-I GO:0004030 aldehyde dehydrogenase [NAD(P)+] activity ARBA:ARBA00028733 MODIFY general (21-200) 54 NEEDS_MORE_SPECIFIC true but uninformative replacement term UniProt EC mapping supports the NAD+-specific child GO:0004029, but does not establish a specific aldehyde substrate. PSEPK/aldB-II GO:0004030 aldehyde dehydrogenase [NAD(P)+] activity ARBA:ARBA00028733 KEEP_AS_NON_CORE general (21-200) 54 PSEPK/algC GO:1901137 carbohydrate derivative biosynthetic process ARBA:ARBA00026302 KEEP_AS_NON_CORE very general (>200 descendants) 296 PSEPK/algL GO:0016837 carbon-oxygen lyase activity, acting on polysaccharides ARBA:ARBA00026982 MARK_AS_OVER_ANNOTATED general (21-200) 29 TOO_GENERAL true but uninformative more informative The valid substrate-specific GO:0045135 term is more informative. PSEPK/argA GO:0140085 L-amino-acid N-acetyltransferase activity ARBA:ARBA00084890 MARK_AS_OVER_ANNOTATED specific (1-20) 11 UNCLASSIFIED unclassified GO:0004042 identifies both the amino-acid substrate class and acetyl-CoA donor. PSEPK/argH GO:0016829 lyase activity ARBA:ARBA00026870 MARK_AS_OVER_ANNOTATED very general (>200 descendants) 548 TOO_GENERAL true but uninformative captures the GO:0004056 captures the substrate-specific reaction. PSEPK/aroA GO:0016628 oxidoreductase activity, acting on the CH-CH group of donors, NAD or NADP as acceptor ARBA:ARBA00028471 MARK_AS_OVER_ANNOTATED general (21-200) 104 TOO_GENERAL true but uninformative grouping A grouping parent of the specific prephenate dehydrogenase activities. The better-evidenced leaf term GO:0008977 (NAD+) is retained, so this mid-level class is redundant over-annotation. PSEPK/aroE GO:0016491 oxidoreductase activity ARBA:ARBA00028747 MARK_AS_OVER_ANNOTATED very general (>200 descendants) 1810 TOO_GENERAL true but uninformative Redundant Redundant general grouping term; the specific molecular function (GO:0004764) is already present and should be retained as the informative annotation. PSEPK/aroE__Q88IJ7 GO:0016491 oxidoreductase activity ARBA:ARBA00028747 MARK_AS_OVER_ANNOTATED very general (>200 descendants) 1810 TOO_GENERAL true but uninformative captures the The specific term GO:0004764 already captures the molecular function. The parent oxidoreductase term adds little useful functional information. PSEPK/aroE__Q88K85 GO:0016491 oxidoreductase activity ARBA:ARBA00028747 MARK_AS_OVER_ANNOTATED very general (>200 descendants) 1810 TOO_GENERAL true but uninformative captures the The specific term GO:0004764 already captures the molecular function. The parent oxidoreductase term adds little useful functional information. PSEPK/aroE__Q88RQ5 GO:0016491 oxidoreductase activity ARBA:ARBA00028747 MARK_AS_OVER_ANNOTATED very general (>200 descendants) 1810 TOO_GENERAL true but uninformative captures the The specific term GO:0004764 already captures the molecular function. The parent oxidoreductase term adds little useful functional information. PSEPK/aroF-I GO:0042802 identical protein binding ARBA:ARBA00027930 MARK_AS_OVER_ANNOTATED specific (1-20) 1 TOO_GENERAL true but uninformative adds little The annotation adds little beyond the catalytic DAHP synthase activity and appears electronically propagated. Generic protein-binding-style terms are not useful as core molecular functions here. PSEPK/aroF-II GO:0042802 identical protein binding ARBA:ARBA00027930 MARK_AS_OVER_ANNOTATED specific (1-20) 1 TOO_GENERAL true but uninformative adds little The annotation adds little beyond the catalytic DAHP synthase activity and appears electronically propagated. Generic protein-binding-style terms are not useful as core molecular functions here. PSEPK/aruC GO:0008483 transaminase activity ARBA:ARBA00028950 MARK_AS_OVER_ANNOTATED general (21-200) 91 UNCLASSIFIED unclassified GO:0003992 provides the informative predicted reaction. PSEPK/bdhA GO:0016616 oxidoreductase activity, acting on the CH-OH group of donors, NAD or NADP as acceptor ARBA:ARBA00028442 ACCEPT very general (>200 descendants) 364 PSEPK/bioC GO:0008168 methyltransferase activity ARBA:ARBA00028302 MARK_AS_OVER_ANNOTATED very general (>200 descendants) 376 UNCLASSIFIED unclassified GO:0008168 does not identify the malonyl-ACP substrate or BioC pathway role captured by GO:0102130. PSEPK/bioD GO:0042803 protein homodimerization activity ARBA:ARBA00027933 MARK_AS_OVER_ANNOTATED leaf (0) 0 TOO_GENERAL true but uninformative generic The BioD reaction is fully captured by GO:0004141; generic self-association adds little functional information. PSEPK/calA GO:0008106 alcohol dehydrogenase (NADP+) activity ARBA:ARBA00092671 KEEP_AS_NON_CORE specific (1-20) 9 PSEPK/carB GO:0006520 amino acid metabolic process ARBA:ARBA00026411 MARK_AS_OVER_ANNOTATED general (21-200) 183 UNCLASSIFIED unclassified Retain the specific L-arginine biosynthetic process. PSEPK/catB GO:0003824 catalytic activity ARBA:ARBA00027533 MARK_AS_OVER_ANNOTATED very general (>200 descendants) 6405 TOO_GENERAL true but uninformative generic A highly specific catalytic term is already present, making the generic parent term redundant. PSEPK/catB GO:0006518 peptide metabolic process ARBA:ARBA00026402 REMOVE general (21-200) 38 WRONG_PROCESS wrong manual WRONG_PROCESS CatB is a muconate cycloisomerase in aromatic compound catabolism, not a peptide metabolic enzyme. PSEPK/cbcV GO:0006970 response to osmotic stress ARBA:ARBA00026252 MARK_AS_OVER_ANNOTATED general (21-200) 29 UNCLASSIFIED unclassified Characterized Cbc systems primarily import quaternary amines for catabolism under low-osmolarity conditions; osmoprotection is context dependent. PSEPK/cca GO:0042780 tRNA 3'-end processing ARBA:ARBA00028910 ACCEPT specific (1-20) 3 PSEPK/ccmH GO:0016020 membrane ARBA:ARBA00028763 MARK_AS_OVER_ANNOTATED very general (>200 descendants) 895 TOO_GENERAL true but uninformative Redundant Redundant, less precise parent of the plasma-membrane annotation. PSEPK/ccmH GO:0017004 cytochrome complex assembly ARBA:ARBA00086146 MODIFY specific (1-20) 9 OTHER_TERM different term needed replacement term GO:1903607 directly names biosynthesis of the c-type cytochrome product, whereas GO:0017004 describes assembly of a cytochrome-containing complex. PSEPK/chrR GO:0016655 oxidoreductase activity, acting on NAD(P)H, quinone or similar compound as acceptor ARBA:ARBA00027020 MARK_AS_OVER_ANNOTATED specific (1-20) 10 UNCLASSIFIED unclassified Retain the specific NADH/NADPH quinone-reductase activities instead. PSEPK/clpB GO:0005829 cytosol ARBA:ARBA00029243 KEEP_AS_NON_CORE general (21-200) 73 PSEPK/clpB GO:0042802 identical protein binding ARBA:ARBA00027930 KEEP_AS_NON_CORE specific (1-20) 1 PSEPK/clsA GO:0030572 phosphatidyltransferase activity ARBA:ARBA00043336 MODIFY specific (1-20) 3 NEEDS_MORE_SPECIFIC true but uninformative replacement term Use cardiolipin synthase activity for the named Cls paralog. PSEPK/clsB GO:0030572 phosphatidyltransferase activity ARBA:ARBA00043336 MODIFY specific (1-20) 3 NEEDS_MORE_SPECIFIC true but uninformative replacement term Use cardiolipin synthase activity for the named Cls paralog. PSEPK/cysE GO:0016413 O-acetyltransferase activity ARBA:ARBA00034208 KEEP_AS_NON_CORE general (21-200) 28 PSEPK/cysK GO:0003824 catalytic activity ARBA:ARBA00027533 KEEP_AS_NON_CORE very general (>200 descendants) 6405 PSEPK/cysM GO:0003824 catalytic activity ARBA:ARBA00027533 KEEP_AS_NON_CORE very general (>200 descendants) 6405 PSEPK/davD GO:0016620 oxidoreductase activity, acting on the aldehyde or oxo group of donors, NAD or NADP as acceptor ARBA:ARBA00028482 MARK_AS_OVER_ANNOTATED general (21-200) 80 TOO_GENERAL true but uninformative captures the GO:0102810 captures the physiological substrate and NADP dependence. PSEPK/davT GO:0019477 L-lysine catabolic process ARBA:ARBA00084340 ACCEPT specific (1-20) 1 PSEPK/ddl GO:0016881 acid-amino acid ligase activity ARBA:ARBA00028624 MARK_AS_OVER_ANNOTATED general (21-200) 54 TOO_GENERAL true but uninformative uninformative This uninformative parent adds no value beyond the exact GO:0008716 D-alanine-D-alanine ligase reaction accepted for the same protein. PSEPK/dinB GO:0006259 DNA metabolic process ARBA:ARBA00028839 MARK_AS_OVER_ANNOTATED very general (>200 descendants) 285 TOO_GENERAL true but uninformative high-level DNA metabolic process is a high-level parent of the specific DNA repair and translesion synthesis terms already annotated, so it adds no informative content. PSEPK/dnaA GO:0016887 ATP hydrolysis activity ARBA:ARBA00043426 ACCEPT leaf (0) 0 PSEPK/dnaE2 GO:0006974 DNA damage response ARBA:ARBA00026271 KEEP_AS_NON_CORE general (21-200) 95 PSEPK/dnaN GO:0042802 identical protein binding ARBA:ARBA00027930 MARK_AS_OVER_ANNOTATED specific (1-20) 1 UNCLASSIFIED unclassified DnaN forms a homodimeric ring, but its biologically meaningful role is sliding-clamp processivity. PSEPK/dnaQ GO:0004527 exonuclease activity ARBA:ARBA00029226 MARK_AS_OVER_ANNOTATED general (21-200) 26 UNCLASSIFIED unclassified GO:0008408 supplies the biologically relevant 3'-to-5' directionality. PSEPK/dsbA GO:0015036 disulfide oxidoreductase activity ARBA:ARBA00026549 MODIFY specific (1-20) 14 NEEDS_MORE_SPECIFIC true but uninformative replacement term The exact Q88RK2 record identifies a DsbA-family thiol-disulfide interchange protein with the canonical active-site disulfide. GO:0015036 captures disulfide oxidoreductase chemistry broadly; GO:0015035 is the more specific protein-disulfide oxidoreductase term for DsbA-catalyzed thiol-disulfide exchange with exported substrates. PSEPK/efp GO:0005829 cytosol ARBA:ARBA00029243 ACCEPT general (21-200) 73 PSEPK/efp GO:0006417 regulation of translation ARBA:ARBA00027123 KEEP_AS_NON_CORE general (21-200) 122 PSEPK/efp GO:0072344 rescue of stalled cytosolic ribosome ARBA:ARBA00043322 ACCEPT specific (1-20) 4 PSEPK/fabB GO:0016747 acyltransferase activity, transferring groups other than amino-acyl groups ARBA:ARBA00027717 MARK_AS_OVER_ANNOTATED very general (>200 descendants) 345 UNCLASSIFIED unclassified The 3-oxoacyl-ACP synthase term captures FabB substrate and chemistry. PSEPK/fabG GO:0030497 fatty acid elongation ARBA:ARBA00028259 ACCEPT specific (1-20) 4 PSEPK/folD1 GO:0016491 oxidoreductase activity ARBA:ARBA00028747 KEEP_AS_NON_CORE very general (>200 descendants) 1810 PSEPK/folD2 GO:0005737 cytoplasm ARBA:ARBA00026971 MARK_AS_OVER_ANNOTATED very general (>200 descendants) 1146 TOO_GENERAL true but uninformative captures the Mark GO:0005737 as over-annotated because the accepted GO:0005829 child already captures the supported soluble compartment more precisely; the parent location adds no independent localization information. PSEPK/folD2 GO:0016491 oxidoreductase activity ARBA:ARBA00028747 KEEP_AS_NON_CORE very general (>200 descendants) 1810 PSEPK/fruK GO:0016052 carbohydrate catabolic process ARBA:ARBA00028828 MODIFY general (21-200) 116 NEEDS_MORE_SPECIFIC true but uninformative replacement term GO:0006001 is the informative child process for the FruK reaction. PSEPK/gabD-II GO:0016620 oxidoreductase activity, acting on the aldehyde or oxo group of donors, NAD or NADP as acceptor ARBA:ARBA00028482 KEEP_AS_NON_CORE general (21-200) 80 PSEPK/galA GO:0016702 oxidoreductase activity, acting on single donors with incorporation of molecular oxygen, incorporation of two atoms of oxygen ARBA:ARBA00027642 KEEP_AS_NON_CORE general (21-200) 72 PSEPK/galC GO:0016833 oxo-acid-lyase activity ARBA:ARBA00026979 KEEP_AS_NON_CORE general (21-200) 25 PSEPK/galC GO:0019336 phenol-containing compound catabolic process ARBA:ARBA00027340 MARK_AS_OVER_ANNOTATED general (21-200) 62 TOO_GENERAL true but uninformative more precise The direct pathway term GO:0019396 gallate catabolic process is more precise and experimentally supported. PSEPK/galC GO:0042537 benzene-containing compound metabolic process ARBA:ARBA00027366 MARK_AS_OVER_ANNOTATED general (21-200) 105 TOO_GENERAL true but uninformative broad GalC should be annotated to gallate catabolism rather than this broad aromatic compound metabolism term. PSEPK/galC GO:0072329 monocarboxylic acid catabolic process ARBA:ARBA00027114 MARK_AS_OVER_ANNOTATED general (21-200) 88 TOO_GENERAL true but uninformative broad The characterized pathway is gallate catabolism; this broad process should not be retained as the functional conclusion. PSEPK/gatA GO:0005737 cytoplasm ARBA:ARBA00026971 KEEP_AS_NON_CORE very general (>200 descendants) 1146 PSEPK/gbd GO:0016616 oxidoreductase activity, acting on the CH-OH group of donors, NAD or NADP as acceptor ARBA:ARBA00028442 MODIFY very general (>200 descendants) 364 NEEDS_MORE_SPECIFIC true but uninformative replacement term Replace it with GO:0047577, which preserves the independently supported Group III Fe-ADH chemistry while adding the submitted substrate specificity; the latter remains a prediction for Q88JJ9. PSEPK/gdhA GO:0004353 L-glutamate dehydrogenase [NAD(P)+] activity ARBA:ARBA00026338 KEEP_AS_NON_CORE specific (1-20) 2 PSEPK/glaH GO:0016706 2-oxoglutarate-dependent dioxygenase activity ARBA:ARBA00027633 MARK_AS_OVER_ANNOTATED general (21-200) 65 TOO_GENERAL true but uninformative parent Correct parent activity but less specific than the glutarate dioxygenase activity term, which is present. PSEPK/glcF GO:0016491 oxidoreductase activity ARBA:ARBA00028747 MARK_AS_OVER_ANNOTATED very general (>200 descendants) 1810 UNCLASSIFIED unclassified Glycolate dehydrogenase contribution and 4Fe-4S cluster binding better capture GlcF function. PSEPK/glgB GO:0044042 glucan metabolic process ARBA:ARBA00027007 MARK_AS_OVER_ANNOTATED general (21-200) 62 TOO_GENERAL true but uninformative broad The term is correct but broad and redundant with the more informative glycogen biosynthetic process and branching-enzyme activity. PSEPK/glgP GO:0005977 glycogen metabolic process ARBA:ARBA00028497 KEEP_AS_NON_CORE specific (1-20) 3 PSEPK/glmU GO:0016779 nucleotidyltransferase activity ARBA:ARBA00026258 MARK_AS_OVER_ANNOTATED general (21-200) 106 UNCLASSIFIED unclassified Retain GO:0003977 instead. PSEPK/gshA GO:0016879 ligase activity, forming carbon-nitrogen bonds ARBA:ARBA00028601 MARK_AS_OVER_ANNOTATED general (21-200) 113 UNCLASSIFIED unclassified GO:0004357 identifies the physiological substrates and should carry the core function. PSEPK/gshB GO:0003824 catalytic activity ARBA:ARBA00027533 MARK_AS_OVER_ANNOTATED very general (>200 descendants) 6405 TOO_GENERAL true but uninformative captures the GO:0004363 captures the substrate-specific glutathione-forming reaction. PSEPK/gyrA GO:0034335 DNA negative supercoiling activity ARBA:ARBA00029159 ACCEPT leaf (0) 0 PSEPK/gyrA GO:0051276 chromosome organization ARBA:ARBA00028775 KEEP_AS_NON_CORE general (21-200) 125 PSEPK/gyrB GO:0051276 chromosome organization ARBA:ARBA00028775 KEEP_AS_NON_CORE general (21-200) 125 PSEPK/hemB GO:0006779 porphyrin-containing compound biosynthetic process ARBA:ARBA00027896 KEEP_AS_NON_CORE specific (1-20) 16 PSEPK/hemBB GO:0006779 porphyrin-containing compound biosynthetic process ARBA:ARBA00027896 KEEP_AS_NON_CORE specific (1-20) 16 PSEPK/hemE GO:0006778 porphyrin-containing compound metabolic process ARBA:ARBA00027898 KEEP_AS_NON_CORE general (21-200) 33 PSEPK/hisB GO:0003824 catalytic activity ARBA:ARBA00027533 MARK_AS_OVER_ANNOTATED very general (>200 descendants) 6405 TOO_GENERAL true but uninformative generic GO:0003824 is a generic ancestor of the specific imidazoleglycerol-phosphate dehydratase activity already annotated. PSEPK/hisC GO:0140385 amino acid transaminase activity ARBA:ARBA00096929 MARK_AS_OVER_ANNOTATED general (21-200) 46 TOO_GENERAL true but uninformative Generic Generic ancestor of the specific histidinol-phosphate transaminase activity; the more precise term GO:0004400 already captures this function. PSEPK/hisI GO:0004636 phosphoribosyl-ATP diphosphatase activity ARBA:ARBA00088319 REMOVE leaf (0) 0 WRONG_ACTIVITY wrong manual WRONG_ACTIVITY This ARBA assignment appears to have propagated across a family that also contains bifunctional HisIE proteins. Q88D15 is a 130-residue standalone phosphoribosyl-AMP cyclohydrolase, whereas adjacent Q88D14 is the reviewed standalone phosphoribosyl-ATP diphosphatase with EC 3.6.1.31 and RHEA:22828. PSEPK/hldE GO:0016772 transferase activity, transferring phosphorus-containing groups ARBA:ARBA00026261 MARK_AS_OVER_ANNOTATED very general (>200 descendants) 567 UNCLASSIFIED unclassified The exact kinase and adenylyltransferase terms should carry the core assertions. PSEPK/ilvH GO:0005737 cytoplasm ARBA:ARBA00026971 MARK_AS_OVER_ANNOTATED very general (>200 descendants) 1146 TOO_GENERAL true but uninformative broad GO:0005829 is the only localization assertion propagated to this record; the UniProt record has no independent SUBCELLULAR LOCATION line for the broader cytoplasm parent. Mark the parent as redundant here and retain the directly supported cytosol child. PSEPK/iscU GO:0005737 cytoplasm ARBA:ARBA00026971 KEEP_AS_NON_CORE very general (>200 descendants) 1146 PSEPK/ivd GO:0016937 short-chain fatty acyl-CoA dehydrogenase activity ARBA:ARBA00044591 MARK_AS_OVER_ANNOTATED specific (1-20) 2 UNCLASSIFIED unclassified Do not treat the short-chain activity as the physiological core function; retain the exact 3-methylbutanoyl-CoA dehydrogenase activity as core. PSEPK/kdpD GO:0005737 cytoplasm ARBA:ARBA00026971 REMOVE very general (>200 descendants) 1146 WRONG_LOCATION wrong manual WRONG_LOCATION The UniProt record places full-length KdpD in the membrane as a multipass membrane protein. Its large cytosolic input and transmitter domains explain the inference but do not make the whole protein a cytoplasmic gene product, so the ARBA assignment is a localization overreach. PSEPK/kdpE GO:0000987 cis-regulatory region sequence-specific DNA binding ARBA:ARBA00029010 ACCEPT specific (1-20) 18 PSEPK/kdpE GO:0042802 identical protein binding ARBA:ARBA00027930 MARK_AS_OVER_ANNOTATED specific (1-20) 1 TOO_GENERAL true but uninformative Generic Generic self-binding is uninformative and does not establish the regulatory mechanism. PSEPK/kdpE GO:0045893 positive regulation of DNA-templated transcription ARBA:ARBA00029082 ACCEPT general (21-200) 42 PSEPK/kdsA1 GO:0046394 carboxylic acid biosynthetic process ARBA:ARBA00027883 MARK_AS_OVER_ANNOTATED very general (>200 descendants) 208 UNCLASSIFIED unclassified GO:0019294 is the relevant substrate-specific biosynthetic process. PSEPK/kguK GO:0016773 phosphotransferase activity, alcohol group as acceptor ARBA:ARBA00026265 MARK_AS_OVER_ANNOTATED very general (>200 descendants) 311 UNCLASSIFIED unclassified The exact dehydrogluconokinase term is present. PSEPK/lcdH GO:0042413 carnitine catabolic process ARBA:ARBA00087193 ACCEPT leaf (0) 0 PSEPK/lepB GO:0008233 peptidase activity ARBA:ARBA00027408 MARK_AS_OVER_ANNOTATED general (21-200) 81 TOO_GENERAL true but uninformative broad This very broad parent adds no information beyond GO:0009003. PSEPK/leuC GO:0043436 oxoacid metabolic process ARBA:ARBA00027279 MARK_AS_OVER_ANNOTATED very general (>200 descendants) 571 TOO_GENERAL true but uninformative captures the GO:0009098 captures the specific biological pathway. PSEPK/lpd GO:0045333 cellular respiration ARBA:ARBA00026750 MARK_AS_OVER_ANNOTATED general (21-200) 50 UNCLASSIFIED unclassified The ARBA process call exceeds the exact dihydrolipoyl dehydrogenase chemistry supported by the record. PSEPK/lpd GO:1990234 transferase complex ARBA:ARBA00026800 KEEP_AS_NON_CORE very general (>200 descendants) 309 PSEPK/lysA-I GO:0016831 carboxy-lyase activity ARBA:ARBA00026976 MARK_AS_OVER_ANNOTATED general (21-200) 99 TOO_GENERAL true but uninformative captures the GO:0008836 captures the substrate-specific decarboxylation. PSEPK/lysS GO:0042803 protein homodimerization activity ARBA:ARBA00027933 KEEP_AS_NON_CORE leaf (0) 0 PSEPK/mazG GO:0006950 response to stress ARBA:ARBA00026300 UNDECIDED very general (>200 descendants) 590 PSEPK/metB GO:0003824 catalytic activity ARBA:ARBA00027533 MODIFY very general (>200 descendants) 6405 NEEDS_MORE_SPECIFIC true but uninformative replacement term The protein name and pathway context support cystathionine gamma-synthase activity, which is more specific than the ARBA catalytic activity parent. PSEPK/metZ GO:0003824 catalytic activity ARBA:ARBA00027533 MODIFY very general (>200 descendants) 6405 NEEDS_MORE_SPECIFIC true but uninformative replacement term UniProt assigns the specific O-succinylhomoserine sulfhydrylase reaction and the GOA table already includes a more informative carbon-sulfur lyase activity annotation. PSEPK/mlaF GO:0006869 lipid transport ARBA:ARBA00027046 MODIFY general (21-200) 174 NEEDS_MORE_SPECIFIC true but uninformative replacement term MlaF supplies ATP-dependent energy coupling to phospholipid transport, and GO:0015914 captures that process more specifically than generic lipid transport. PSEPK/moaE GO:0032324 molybdopterin cofactor biosynthetic process ARBA:ARBA00043347 MARK_AS_OVER_ANNOTATED specific (1-20) 5 TOO_GENERAL true but uninformative more precise GO:0006777 more precisely captures the conserved cofactor-biosynthesis route containing the MoaE molybdopterin-forming step. PSEPK/moeB GO:0003824 catalytic activity ARBA:ARBA00027533 MODIFY very general (>200 descendants) 6405 NEEDS_MORE_SPECIFIC true but uninformative replacement term Catalysis is central to this enzyme, but GO:0003824 does not identify the reaction. Use the specific molecular function already supported elsewhere in this review; this is a specificity refinement, not a claim that catalysis is peripheral or absent. PSEPK/mqo1 GO:0016614 oxidoreductase activity, acting on CH-OH group of donors ARBA:ARBA00028437 KEEP_AS_NON_CORE very general (>200 descendants) 457 PSEPK/mqo2 GO:0016614 oxidoreductase activity, acting on CH-OH group of donors ARBA:ARBA00028437 KEEP_AS_NON_CORE very general (>200 descendants) 457 PSEPK/mqo3 GO:0016614 oxidoreductase activity, acting on CH-OH group of donors ARBA:ARBA00028437 KEEP_AS_NON_CORE very general (>200 descendants) 457 PSEPK/mupP GO:0016791 phosphatase activity ARBA:ARBA00026393 ACCEPT general (21-200) 170 PSEPK/murG GO:1901137 carbohydrate derivative biosynthetic process ARBA:ARBA00026302 MARK_AS_OVER_ANNOTATED very general (>200 descendants) 296 UNCLASSIFIED unclassified Peptidoglycan biosynthesis is the direct and informative process for MurG. PSEPK/murU GO:0016779 nucleotidyltransferase activity ARBA:ARBA00026258 MODIFY general (21-200) 106 NEEDS_MORE_SPECIFIC true but uninformative replacement term GO:0070569 is the specific child term for the MurU reaction. Falcon deep research confirms MurU is specifically a uridylyltransferase that generates UDP-MurNAc, so the generic nucleotidyltransferase parent is less informative. PSEPK/mutL GO:0006259 DNA metabolic process ARBA:ARBA00028839 MARK_AS_OVER_ANNOTATED very general (>200 descendants) 285 UNCLASSIFIED unclassified GO:0006298 is the direct pathway term. PSEPK/nadD GO:0009165 nucleotide biosynthetic process ARBA:ARBA00027613 MODIFY general (21-200) 114 NEEDS_MORE_SPECIFIC true but uninformative replacement term NadD specifically participates in NAD+ biosynthesis. PSEPK/nadD GO:0070566 adenylyltransferase activity ARBA:ARBA00028518 MODIFY general (21-200) 23 NEEDS_MORE_SPECIFIC true but uninformative replacement term GO:0004515 identifies NaMN as the adenylyl acceptor. PSEPK/nadE GO:0016879 ligase activity, forming carbon-nitrogen bonds ARBA:ARBA00028601 MODIFY general (21-200) 113 NEEDS_MORE_SPECIFIC true but uninformative replacement term GO:0008795 captures the NAD+ synthase reaction and correct nitrogen-donor class. PSEPK/nicC GO:1901848 nicotinate catabolic process ARBA:ARBA00091462 ACCEPT leaf (0) 0 PSEPK/nuoC GO:0022904 respiratory electron transport chain ARBA:ARBA00033493 ACCEPT specific (1-20) 12 PSEPK/nuoE GO:0030964 NADH dehydrogenase complex ARBA:ARBA00027021 ACCEPT specific (1-20) 2 PSEPK/nuoE GO:0051537 2 iron, 2 sulfur cluster binding ARBA:ARBA00026418 ACCEPT leaf (0) 0 PSEPK/nuoF GO:0045271 respiratory chain complex I ARBA:ARBA00027636 ACCEPT leaf (0) 0 PSEPK/paaF GO:0016836 hydro-lyase activity ARBA:ARBA00026984 MARK_AS_OVER_ANNOTATED general (21-200) 120 UNCLASSIFIED unclassified Enoyl-CoA hydratase activity is the informative child term. PSEPK/paaG GO:0003824 catalytic activity ARBA:ARBA00027533 MODIFY very general (>200 descendants) 6405 NEEDS_MORE_SPECIFIC true but uninformative replacement term UniProt assigns PaaG as a 1,2-epoxyphenylacetyl-CoA isomerase. PSEPK/paaH GO:0003824 catalytic activity ARBA:ARBA00027533 MARK_AS_OVER_ANNOTATED very general (>200 descendants) 6405 UNCLASSIFIED unclassified UniProt assigns PaaH as an NAD-dependent 3-hydroxyacyl-CoA dehydrogenase. PSEPK/paaH GO:0032787 monocarboxylic acid metabolic process ARBA:ARBA00027288 MARK_AS_OVER_ANNOTATED very general (>200 descendants) 286 UNCLASSIFIED unclassified The specific physiological role is phenylacetate catabolism. PSEPK/paaJ GO:0005737 cytoplasm ARBA:ARBA00026971 ACCEPT very general (>200 descendants) 1146 PSEPK/pbpG GO:0008233 peptidase activity ARBA:ARBA00027408 MODIFY general (21-200) 81 NEEDS_MORE_SPECIFIC true but uninformative replacement term GO:0061785 identifies both the endopeptidase reaction and peptidoglycan substrate. PSEPK/pcaB GO:0016829 lyase activity ARBA:ARBA00026870 MARK_AS_OVER_ANNOTATED very general (>200 descendants) 548 TOO_GENERAL true but uninformative generic The review should retain the specific catalytic term rather than a generic parent. GO:0016829 adds little beyond indicating broad enzyme class, while GO:0047472 identifies the actual substrate-level reaction. PSEPK/pcaF GO:0003988 acetyl-CoA C-acyltransferase activity ARBA:ARBA00043303 KEEP_AS_NON_CORE specific (1-20) 2 PSEPK/pcaF GO:0006629 lipid metabolic process ARBA:ARBA00028591 REMOVE very general (>200 descendants) 608 WRONG_PROCESS wrong manual WRONG_PROCESS This appears to be a family-level ARBA over-projection from thiolase chemistry. The target record places PcaF-I in aromatic beta-ketoadipate catabolism. The structural paper does show broad acyl-chain accommodation, but its long-chain ligands were trapped in active-site mutants under crystallographic soaking conditions; that in vitro promiscuity does not establish a physiological lipid-metabolism role. PSEPK/pedH GO:0020037 heme binding ARBA:ARBA00026797 REMOVE leaf (0) 0 WRONG_ACTIVITY wrong manual WRONG_ACTIVITY Incorrect annotation. PedH is a PQQ quinoprotein rather than a heme-containing enzyme. A cytochrome c is the assigned reaction acceptor, not a prosthetic group bound by PedH. PSEPK/pedH GO:0070968 pyrroloquinoline quinone binding ARBA:ARBA00086199 ACCEPT leaf (0) 0 PSEPK/pedI GO:0004030 aldehyde dehydrogenase [NAD(P)+] activity ARBA:ARBA00028733 MARK_AS_OVER_ANNOTATED general (21-200) 54 INDIRECT_EFFECT overreach downstream The annotation is too broad for the available evidence. The curated view is that PP_2680 is a PedI ortholog with a specific role in aldehyde oxidation downstream of alcohol oxidation pathways, not just any NAD(P)-dependent aldehyde dehydrogenase. PSEPK/pede GO:0016491 oxidoreductase activity ARBA:ARBA00028747 ACCEPT very general (>200 descendants) 1810 PSEPK/pede GO:0020037 heme binding ARBA:ARBA00026797 REMOVE leaf (0) 0 WRONG_ACTIVITY wrong manual WRONG_ACTIVITY PedE is a quinoprotein, not a quinohemoprotein. The UniProt entry lists only PQQ and Ca2+ cofactors, while its specific physiological cytochrome c partner is assigned by similarity and remains a separate protein. PSEPK/pede GO:0070968 pyrroloquinoline quinone binding ARBA:ARBA00086199 ACCEPT leaf (0) 0 PSEPK/pgsA GO:0005737 cytoplasm ARBA:ARBA00026971 REMOVE very general (>200 descendants) 1146 WRONG_LOCATION wrong manual WRONG_LOCATION PgsA is an integral membrane enzyme. UniProt records it as a membrane, multi-pass protein, Phobius predicts four transmembrane helices (6..23, 71..97, 133..151, 157..176), and the donor substrate CDP-diacylglycerol is a bilayer lipid, so catalysis occurs at the membrane surface rather than free in the cytosol. This row comes from an ARBA machine-learned model with no supporting feature anywhere in the entry, while the plasma membrane and membrane rows in the same GOA set already record the correct compartment. No soluble cytoplasmic form of a class-I CDP-alcohol phosphatidyltransferase is known, so this is a localization overcall rather than a second genuine location. PSEPK/pgsA GO:0008610 lipid biosynthetic process ARBA:ARBA00027236 MODIFY very general (>200 descendants) 258 NEEDS_MORE_SPECIFIC true but uninformative replacement term Use glycerophospholipid biosynthetic process for this phosphatidylglycerol-branch enzyme. PSEPK/pgsA GO:0019637 organophosphate metabolic process ARBA:ARBA00028049 MARK_AS_OVER_ANNOTATED very general (>200 descendants) 627 TOO_GENERAL true but uninformative generic The useful annotation is glycerophospholipid/phosphatidylglycerol biosynthesis, not a generic organophosphate process. PSEPK/pgsA GO:0036094 small molecule binding ARBA:ARBA00028778 MARK_AS_OVER_ANNOTATED very general (>200 descendants) 302 UNCLASSIFIED unclassified The catalytic phosphatidyltransferase activity is the informative molecular function. PSEPK/pgsA GO:0050793 regulation of developmental process ARBA:ARBA00028689 REMOVE very general (>200 descendants) 1542 WRONG_PROCESS wrong manual WRONG_PROCESS This appears to be an ARBA over-propagation unrelated to the membrane phospholipid enzyme identity. PSEPK/pheA GO:0016836 hydro-lyase activity ARBA:ARBA00026984 MARK_AS_OVER_ANNOTATED general (21-200) 120 TOO_GENERAL true but uninformative parent Intermediate parent of prephenate dehydratase activity within the lyase branch. Less informative than the specific child term GO:0004664, which is annotated. PSEPK/phnX GO:0003824 catalytic activity ARBA:ARBA00027533 MODIFY very general (>200 descendants) 6405 NEEDS_MORE_SPECIFIC true but uninformative replacement term Q88KT1 has a substrate- and reaction-specific annotation supported by EC 3.11.1.1, RHEA:18905, HAMAP MF_01375, and InterPro IPR006323. PSEPK/pobA GO:0016709 oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, NAD(P)H as one donor, and incorporation of one atom of oxygen ARBA:ARBA00027634 MARK_AS_OVER_ANNOTATED general (21-200) 110 TOO_GENERAL true but uninformative redundant The annotation is redundant with the more precise 4-hydroxybenzoate 3-monooxygenase activity term and adds little biological specificity. PSEPK/ppsA GO:0016740 transferase activity ARBA:ARBA00027723 MARK_AS_OVER_ANNOTATED very general (>200 descendants) 2172 TOO_GENERAL true but uninformative Root Root-level transferase term assigned by ARBA. Correct (PEP synthase is a phosphotransferase) but entirely uninformative relative to the specific EC 2.7.9.2 activity already annotated. PSEPK/proB GO:0008652 amino acid biosynthetic process ARBA:ARBA00027355 MODIFY general (21-200) 52 NEEDS_MORE_SPECIFIC true but uninformative replacement term The specific process is L-proline biosynthesis. PSEPK/prpE GO:0005737 cytoplasm ARBA:ARBA00026971 ACCEPT very general (>200 descendants) 1146 PSEPK/prpE GO:0016874 ligase activity ARBA:ARBA00028597 MARK_AS_OVER_ANNOTATED very general (>200 descendants) 234 UNCLASSIFIED unclassified UniProt assigns propionyl-CoA synthetase, EC 6.2.1.17. PSEPK/prpE GO:0070013 intracellular organelle lumen ARBA:ARBA00027917 REMOVE very general (>200 descendants) 239 WRONG_TAXON wrong manual WRONG_TAXON Pseudomonas putida is a bacterium without the membrane-bounded intracellular organelle lumen described by this term. The coexisting cytoplasm annotation is the biologically appropriate localization. PSEPK/pssA GO:0005737 cytoplasm ARBA:ARBA00026971 MARK_AS_OVER_ANNOTATED very general (>200 descendants) 1146 TOO_GENERAL true but uninformative captures the GO:0005829 already captures the soluble compartment at useful specificity. PSEPK/pstS GO:0005576 extracellular region ARBA:ARBA00027128 MODIFY very general (>200 descendants) 276 NEEDS_MORE_SPECIFIC true but uninformative replacement term The N-terminal signal peptide supports export from the cytoplasm, and the mature protein carries the expected periplasmic-binding-protein domain. PSEPK/ptxD GO:0016491 oxidoreductase activity ARBA:ARBA00028747 MARK_AS_OVER_ANNOTATED very general (>200 descendants) 1810 UNCLASSIFIED unclassified GO:0008114 is the appropriate pathway-grounded molecular function. PSEPK/ptxS GO:0001217 DNA-binding transcription repressor activity ARBA:ARBA00027659 ACCEPT specific (1-20) 3 PSEPK/ptxS GO:0032993 protein-DNA complex ARBA:ARBA00028896 ACCEPT general (21-200) 50 PSEPK/purB GO:0016829 lyase activity ARBA:ARBA00026870 MODIFY very general (>200 descendants) 548 NEEDS_MORE_SPECIFIC true but uninformative replacement term Replace the broad lyase parent with both physiological PurB activities. PSEPK/purD GO:0003824 catalytic activity ARBA:ARBA00027533 MODIFY very general (>200 descendants) 6405 NEEDS_MORE_SPECIFIC true but uninformative replacement term Replace the generic catalytic parent with phosphoribosylamine-glycine ligase activity. PSEPK/purE GO:0003824 catalytic activity ARBA:ARBA00027533 MODIFY very general (>200 descendants) 6405 NEEDS_MORE_SPECIFIC true but uninformative replacement term Replace the generic catalytic parent with N5-CAIR mutase activity. PSEPK/purN GO:0003824 catalytic activity ARBA:ARBA00027533 MODIFY very general (>200 descendants) 6405 NEEDS_MORE_SPECIFIC true but uninformative replacement term Replace the generic catalytic parent with phosphoribosylglycinamide formyltransferase activity. PSEPK/purT GO:0003824 catalytic activity ARBA:ARBA00027533 MODIFY very general (>200 descendants) 6405 NEEDS_MORE_SPECIFIC true but uninformative replacement term Replace the generic catalytic parent with the formate-dependent PurT activity. PSEPK/putA GO:0000976 transcription cis-regulatory region binding ARBA:ARBA00028970 ACCEPT general (21-200) 32 PSEPK/putA GO:0001217 DNA-binding transcription repressor activity ARBA:ARBA00027659 ACCEPT specific (1-20) 3 PSEPK/putA GO:0043168 anion binding ARBA:ARBA00026944 MARK_AS_OVER_ANNOTATED general (21-200) 150 TOO_GENERAL true but uninformative parent This ARBA parent-level binding prediction is uninformative beside the two specific catalytic activities and lacks direct KT2440 binding evidence. PSEPK/putA GO:0098562 cytoplasmic side of membrane ARBA:ARBA00027341 KEEP_AS_NON_CORE general (21-200) 23 PSEPK/putA GO:1901363 heterocyclic compound binding ARBA:ARBA00027813 MARK_AS_OVER_ANNOTATED general (21-200) 114 TOO_GENERAL true but uninformative generic Binding of FAD, NAD, and proline is already inherent in the specific catalytic activities; no separate generic binding role is established. PSEPK/puuA-I GO:0016874 ligase activity ARBA:ARBA00028597 MARK_AS_OVER_ANNOTATED very general (>200 descendants) 234 UNCLASSIFIED unclassified Retain the exact substrate-specific molecular function instead. PSEPK/pvdD GO:0072330 monocarboxylic acid biosynthetic process ARBA:ARBA00027175 REMOVE general (21-200) 95 TERM_MISREAD wrong manual TERM_MISREAD The focused structural accounting found that native KT2440 pyoverdine variants carry two or three free carboxylic acid groups. GO:0072330 is therefore chemically inapt, because it describes formation of acids with one carboxyl group. PvdD's direct role is nonribosomal assembly of the pyoverdine peptide scaffold; the ARBA monocarboxylic-acid call is a broad automated over-annotation. PSEPK/pvdT GO:1902495 transmembrane transporter complex ARBA:ARBA00026587 ACCEPT general (21-200) 94 PSEPK/pydA GO:0016491 oxidoreductase activity ARBA:ARBA00028747 MARK_AS_OVER_ANNOTATED very general (>200 descendants) 1810 TOO_GENERAL true but uninformative captures the The specific catalytic term already captures the biologically relevant redox function. PSEPK/pydB GO:0055086 nucleobase-containing small molecule metabolic process ARBA:ARBA00027681 KEEP_AS_NON_CORE very general (>200 descendants) 576 PSEPK/pydB GO:0072529 pyrimidine-containing compound catabolic process ARBA:ARBA00043307 ACCEPT general (21-200) 38 PSEPK/pyrC' GO:0016812 hydrolase activity, acting on carbon-nitrogen (but not peptide) bonds, in cyclic amides ARBA:ARBA00087789 REMOVE specific (1-20) 19 NONCATALYTIC_HOMOLOG wrong manual NONCATALYTIC_HOMOLOG The direct genetic and sequence evidence establishes loss of dihydroorotase catalysis. PSEPK/pyrG GO:0097268 cytoophidium ARBA:ARBA00089783 KEEP_AS_NON_CORE leaf (0) 0 PSEPK/rbsB GO:0055085 transmembrane transport ARBA:ARBA00027679 MODIFY very general (>200 descendants) 1467 NEEDS_MORE_SPECIFIC true but uninformative replacement term The contiguous rbsB-rbsA-I-rbsC-rbsR-rbsK-rbsD locus supports the D-ribose-specific transport process while RbsB contributes substrate capture rather than translocation by itself. PSEPK/rbsK GO:0016772 transferase activity, transferring phosphorus-containing groups ARBA:ARBA00026261 KEEP_AS_NON_CORE very general (>200 descendants) 567 PSEPK/recC GO:0140097 catalytic activity, acting on DNA ARBA:ARBA00027986 REMOVE general (21-200) 148 NONCATALYTIC_HOMOLOG wrong manual NONCATALYTIC_HOMOLOG RecC recognizes DNA and stimulates RecB helicase processivity, whereas RecB and RecD supply motor activity and RecB supplies nuclease catalysis. A generic catalytic-DNA term therefore misrepresents RecC's direct role. PSEPK/relA GO:0015949 nucleobase-containing small molecule interconversion ARBA:ARBA00088782 MODIFY specific (1-20) 10 OTHER_TERM different term needed replacement term The ARBA inference is not wrong but is uninformatively broad. The precise process is (p)ppGpp biosynthesis, which is better captured by the more specific child term, consistent with the GTP diphosphokinase activity and the guanosine tetraphosphate metabolic process annotations. PSEPK/rhlE GO:0009266 response to temperature stimulus ARBA:ARBA00026893 UNDECIDED general (21-200) 25 PSEPK/rnc GO:0042802 identical protein binding ARBA:ARBA00027930 KEEP_AS_NON_CORE specific (1-20) 1 PSEPK/rpe GO:0005737 cytoplasm ARBA:ARBA00026971 KEEP_AS_NON_CORE very general (>200 descendants) 1146 PSEPK/rpoA GO:0005737 cytoplasm ARBA:ARBA00026971 ACCEPT very general (>200 descendants) 1146 PSEPK/rpoC GO:0005829 cytosol ARBA:ARBA00029243 ACCEPT general (21-200) 73 PSEPK/rpoN GO:0000976 transcription cis-regulatory region binding ARBA:ARBA00028970 ACCEPT general (21-200) 32 PSEPK/rpoN GO:0032993 protein-DNA complex ARBA:ARBA00028896 KEEP_AS_NON_CORE general (21-200) 50 PSEPK/ruvA GO:0006974 DNA damage response ARBA:ARBA00026271 KEEP_AS_NON_CORE general (21-200) 95 PSEPK/sad-II GO:0016620 oxidoreductase activity, acting on the aldehyde or oxo group of donors, NAD or NADP as acceptor ARBA:ARBA00028482 KEEP_AS_NON_CORE general (21-200) 80 PSEPK/sbcB GO:0004527 exonuclease activity ARBA:ARBA00029226 MARK_AS_OVER_ANNOTATED general (21-200) 26 UNCLASSIFIED unclassified A direction- and substrate-specific child term is present. PSEPK/serA GO:0006564 L-serine biosynthetic process ARBA:ARBA00093701 ACCEPT leaf (0) 0 PSEPK/serA GO:0047545 (S)-2-hydroxyglutarate dehydrogenase activity ARBA:ARBA00090718 REMOVE specific (1-20) 1 WRONG_ACTIVITY wrong manual WRONG_ACTIVITY The entry assigns (R)-2-hydroxyglutarate dehydrogenase activity (GO:0120568), not the (S)-2-hydroxyglutarate activity represented here. PSEPK/sodB GO:0005737 cytoplasm ARBA:ARBA00026971 ACCEPT very general (>200 descendants) 1146 PSEPK/sodB GO:0046914 transition metal ion binding ARBA:ARBA00027207 MODIFY specific (1-20) 14 NEEDS_MORE_SPECIFIC true but uninformative replacement term `iron ion binding` is the more informative and biologically accurate child term. PSEPK/speC GO:0016831 carboxy-lyase activity ARBA:ARBA00026976 MARK_AS_OVER_ANNOTATED general (21-200) 99 UNCLASSIFIED unclassified GO:0004586 specifies both the ornithine substrate and the decarboxylase reaction and is already present. PSEPK/sucD GO:0042709 succinate-CoA ligase complex ARBA:ARBA00088362 ACCEPT specific (1-20) 2 PSEPK/tatA-II GO:0065002 intracellular protein transmembrane transport ARBA:ARBA00034583 ACCEPT specific (1-20) 10 PSEPK/tatB-I GO:0033281 TAT protein transport complex ARBA:ARBA00092494 ACCEPT leaf (0) 0 PSEPK/tauC GO:0042918 alkanesulfonate transmembrane transport ARBA:ARBA00034185 MODIFY specific (1-20) 5 NEEDS_MORE_SPECIFIC true but uninformative replacement term The submitted product identifies a taurine-specific ABC permease. PSEPK/tktA GO:0009052 pentose-phosphate shunt, non-oxidative branch ARBA:ARBA00091353 ACCEPT leaf (0) 0 PSEPK/trpD GO:0016763 pentosyltransferase activity ARBA:ARBA00026327 KEEP_AS_NON_CORE general (21-200) 74 PSEPK/trpF GO:0046394 carboxylic acid biosynthetic process ARBA:ARBA00027883 MARK_AS_OVER_ANNOTATED very general (>200 descendants) 208 TOO_GENERAL true but uninformative Generic Generic parent term auto-generated from sequence features; the specific L-tryptophan biosynthetic process annotation already captures the biology precisely. PSEPK/ttgB GO:0009636 response to toxic substance ARBA:ARBA00026669 MODIFY general (21-200) 98 NEEDS_MORE_SPECIFIC true but uninformative replacement term While TtgB is indeed involved in response to toxic substances, this term is too vague for the specific efflux-based detoxification mechanism. GO:1990961 (xenobiotic detoxification by transmembrane export across the plasma membrane) precisely describes the mechanism: reducing toxicity by exporting xenobiotics across the plasma membrane. This matches TtgABC's demonstrated function in extruding chloramphenicol (PMID:22143519), bipyridyl compounds (PMID:32973714), and other xenobiotics from KT2440. PSEPK/ttgR GO:0045892 negative regulation of DNA-templated transcription ARBA:ARBA00029084 ACCEPT general (21-200) 39 PSEPK/ubiE GO:0042181 ketone biosynthetic process ARBA:ARBA00027493 MARK_AS_OVER_ANNOTATED general (21-200) 67 UNCLASSIFIED unclassified GO:0006744 identifies the relevant ketone product and pathway. PSEPK/ubiH GO:0003824 catalytic activity ARBA:ARBA00027533 MARK_AS_OVER_ANNOTATED very general (>200 descendants) 6405 TOO_GENERAL true but uninformative captures the GO:0008681 captures the substrate-specific UbiH activity. PSEPK/uvrA GO:0003824 catalytic activity ARBA:ARBA00027533 MARK_AS_OVER_ANNOTATED very general (>200 descendants) 6405 TOO_GENERAL true but uninformative redundant 'catalytic activity' is a top-level placeholder term that conveys no specific mechanistic information. ATP hydrolysis activity is present, making this annotation redundant. PSEPK/uvrA GO:0006974 DNA damage response ARBA:ARBA00026271 MARK_AS_OVER_ANNOTATED general (21-200) 95 TOO_GENERAL true but uninformative broad 'DNA damage response' is a broad ancestor of nucleotide-excision repair. Given the specific NER annotation, this general term adds no curation value. PSEPK/uvrD GO:0042802 identical protein binding ARBA:ARBA00027930 KEEP_AS_NON_CORE specific (1-20) 1 PSEPK/vanA GO:0003824 catalytic activity ARBA:ARBA00027533 MARK_AS_OVER_ANNOTATED very general (>200 descendants) 6405 TOO_GENERAL true but uninformative generic GO:0003824 is a generic parent of the more specific enzyme activity already present. Retaining the parent term adds little value once GO:0018489 is accepted. PSEPK/vdh GO:0016620 oxidoreductase activity, acting on the aldehyde or oxo group of donors, NAD or NADP as acceptor ARBA:ARBA00028482 MODIFY general (21-200) 80 NEEDS_MORE_SPECIFIC true but uninformative replacement term GO:0050608 identifies both the physiological aldehyde and NAD+ acceptor. PSEPK/visC GO:0004497 monooxygenase activity ARBA:ARBA00028788 MARK_AS_OVER_ANNOTATED very general (>200 descendants) 358 TOO_GENERAL true but uninformative captures the GO:0019168 captures the evolved ubiquinone-intermediate hydroxylase function. PSEPK/visC GO:0110142 ubiquinone biosynthesis complex ARBA:ARBA00089351 KEEP_AS_NON_CORE leaf (0) 0 PSEPK/wspR GO:0003824 catalytic activity ARBA:ARBA00027533 MODIFY very general (>200 descendants) 6405 NEEDS_MORE_SPECIFIC true but uninformative replacement term KT2440 studies and foundational WspR biochemistry identify this protein as a diguanylate cyclase. The specific child term is available and should replace the generic parent term. RAMVA/RvY_01767 GO:0098803 respiratory chain complex ARBA:ARBA00029130 REMOVE specific (1-20) 8 WRONG_LOCATION wrong manual WRONG_LOCATION Mitochondrial Mn-SOD is a soluble matrix protein, not part of the respiratory chain complex. The ARBA rule appears to be incorrect for this annotation. SACEN/eryAI GO:0033068 macrolide biosynthetic process ARBA:ARBA00029207 ACCEPT specific (1-20) 4 SACEN/eryAII GO:0033068 macrolide biosynthetic process ARBA:ARBA00029207 ACCEPT specific (1-20) 4 SACEN/eryAIII GO:0033068 macrolide biosynthetic process ARBA:ARBA00029207 ACCEPT specific (1-20) 4 SACEN/eryBV GO:0016758 hexosyltransferase activity ARBA:ARBA00026306 ACCEPT very general (>200 descendants) 337 SACEN/eryBV GO:0017000 antibiotic biosynthetic process ARBA:ARBA00028144 ACCEPT general (21-200) 28 SACEN/eryCIII GO:0016758 hexosyltransferase activity ARBA:ARBA00026306 ACCEPT very general (>200 descendants) 337 SACEN/eryCIII GO:0017000 antibiotic biosynthetic process ARBA:ARBA00028144 ACCEPT general (21-200) 28 SALRS/PTSG_11235 GO:0003824 catalytic activity ARBA:ARBA00027533 KEEP_AS_NON_CORE very general (>200 descendants) 6405 SALRS/PTSG_11235 GO:0016327 apicolateral plasma membrane ARBA:ARBA00086710 REMOVE leaf (0) 0 WRONG_TAXON wrong manual WRONG_TAXON The term describes a membrane domain of polarized epithelial cells, which choanoflagellates do not have. The plasma membrane annotation already captures the defensible location. SALRS/PTSG_11235 GO:0035332 positive regulation of hippo signaling ARBA:ARBA00091325 MARK_AS_OVER_ANNOTATED leaf (0) 0 NO_EVIDENCE overreach without support A regulatory role in Hippo signalling is a specific claim without support in this protein or organism. The term reached it through a machine-learning rule whose features were not inspected. Not removed, since S. rosetta has a Hippo pathway and nothing contradicts a link. SALRS/SrSeptin2 GO:0005737 cytoplasm ARBA:ARBA00026971 ACCEPT very general (>200 descendants) 1146 SALRS/SrSeptin2 GO:0005856 cytoskeleton ARBA:ARBA00029228 ACCEPT very general (>200 descendants) 300 SALRS/warts GO:0071944 cell periphery ARBA:ARBA00027443 UNDECIDED very general (>200 descendants) 493 SCHJY/shc1 GO:0008610 lipid biosynthetic process MODIFY very general (>200 descendants) 258 NEEDS_MORE_SPECIFIC true but uninformative replacement term While technically correct, this term is too broad. The more specific term GO:0019746 (hopanoid biosynthetic process) precisely captures the enzyme function. Hopanoids are a specific class of pentacyclic triterpenoid lipids. SCHJY/shc1 GO:0006629 lipid metabolic process ARBA:ARBA00028591 MODIFY very general (>200 descendants) 608 NEEDS_MORE_SPECIFIC true but uninformative replacement term Same judgment as the EXP lipid metabolic process row; the informative process is hopanoid biosynthetic process (GO:0019746). SCHPO/SPAC8E11.10 GO:0005975 carbohydrate metabolic process ARBA:ARBA00028487 ACCEPT very general (>200 descendants) 321 SCHPO/SPAC8E11.10 GO:0044281 small molecule metabolic process ARBA:ARBA00028529 ACCEPT very general (>200 descendants) 1546 SCHPO/SPAC8E11.10 GO:0050085 mannitol 2-dehydrogenase (NADP+) activity ARBA:ARBA00089119 REMOVE leaf (0) 0 WRONG_ACTIVITY wrong manual WRONG_ACTIVITY "Multiple lines of evidence contradict this annotation. UniProt explicitly names the enzyme ""Sorbose reductase sou1"" with EC 1.1.1.289, which is specific for sorbose/sorbitol interconversion, not mannitol. The deep research states the enzyme ""specifically catalyzes the reversible reaction between L-sorbose and D-sorbitol"" with no mention of mannitol activity. Mannitol and sorbitol are different sugar alcohols (epimers at C2), and the enzyme specificity is for sorbitol, not mannitol. This appears to be an incorrect automated annotation." SCHPO/SPCC18B5.05c GO:0042364 water-soluble vitamin biosynthetic process ARBA:ARBA00029043 MODIFY specific (1-20) 19 NEEDS_MORE_SPECIFIC true but uninformative replacement term Replace the grouping term with the specific process. SCHPO/aah1 GO:0009897 external side of plasma membrane ARBA:ARBA00043397 ACCEPT specific (1-20) 4 SCHPO/alo1 GO:0016491 oxidoreductase activity ARBA:ARBA00028747 KEEP_AS_NON_CORE very general (>200 descendants) 1810 SCHPO/apc2 GO:0000151 ubiquitin ligase complex ARBA:ARBA00029181 ACCEPT general (21-200) 52 SCHPO/apc2 GO:0005634 nucleus ARBA:ARBA00026330 ACCEPT very general (>200 descendants) 473 SCHPO/apc2 GO:0006511 ubiquitin-dependent protein catabolic process ARBA:ARBA00026385 ACCEPT specific (1-20) 18 SCHPO/ark1 GO:0000776 kinetochore ARBA:ARBA00027576 ACCEPT specific (1-20) 11 SCHPO/ark1 GO:0000819 sister chromatid segregation ARBA:ARBA00026649 ACCEPT general (21-200) 29 SCHPO/ark1 GO:0008608 attachment of spindle microtubules to kinetochore ARBA:ARBA00084444 KEEP_AS_NON_CORE specific (1-20) 7 SCHPO/ark1 GO:0032133 chromosome passenger complex ARBA:ARBA00085347 ACCEPT leaf (0) 0 SCHPO/ark1 GO:0032465 regulation of cytokinesis ARBA:ARBA00084247 KEEP_AS_NON_CORE general (21-200) 34 SCHPO/ark1 GO:0044779 meiotic spindle checkpoint signaling ARBA:ARBA00085940 KEEP_AS_NON_CORE specific (1-20) 2 SCHPO/ark1 GO:0045143 homologous chromosome segregation ARBA:ARBA00092722 KEEP_AS_NON_CORE specific (1-20) 19 SCHPO/ark1 GO:0051233 spindle midzone ARBA:ARBA00089348 ACCEPT specific (1-20) 2 SCHPO/ark1 GO:0072479 response to mitotic cell cycle spindle assembly checkpoint signaling ARBA:ARBA00090474 KEEP_AS_NON_CORE specific (1-20) 2 SCHPO/ark1 GO:0090266 regulation of mitotic cell cycle spindle assembly checkpoint ARBA:ARBA00087062 KEEP_AS_NON_CORE specific (1-20) 4 SCHPO/ark1 GO:1902115 regulation of organelle assembly ARBA:ARBA00033491 MARK_AS_OVER_ANNOTATED general (21-200) 57 TOO_GENERAL true but uninformative generic Overly generic electronic inference; the specific role is positive regulation of kinetochore assembly (GO:1905561), already annotated experimentally. SCHPO/ase1 GO:0015630 microtubule cytoskeleton ARBA:ARBA00029268 KEEP_AS_NON_CORE general (21-200) 108 SCHPO/asr1 GO:0000785 chromatin ARBA:ARBA00027601 UNDECIDED general (21-200) 86 SCHPO/asr1 GO:0032991 protein-containing complex ARBA:ARBA00028902 UNDECIDED very general (>200 descendants) 2083 SCHPO/atf1 GO:0000978 RNA polymerase II cis-regulatory region sequence-specific DNA binding ARBA:ARBA00028975 ACCEPT specific (1-20) 12 SCHPO/atf1 GO:0000981 DNA-binding transcription factor activity, RNA polymerase II-specific ARBA:ARBA00029016 ACCEPT specific (1-20) 8 SCHPO/atg13 GO:0000422 autophagy of mitochondrion ARBA:ARBA00026840 ACCEPT specific (1-20) 5 SCHPO/atg13 GO:0016236 macroautophagy ARBA:ARBA00027245 ACCEPT general (21-200) 34 SCHPO/bst1 GO:0005783 endoplasmic reticulum ARBA:ARBA00028672 ACCEPT general (21-200) 100 SCHPO/bub1 GO:0000776 kinetochore ARBA:ARBA00027576 ACCEPT specific (1-20) 11 SCHPO/cdc10 GO:0001228 DNA-binding transcription activator activity, RNA polymerase II-specific ARBA:ARBA00027759 MODIFY leaf (0) 0 OTHER_TERM different term needed replacement term The rule reproduces the family-level activity rather than the subunit-level one. Cdc10 has no demonstrated sequence-specific DNA-binding activity of its own: MCB recognition is supplied by the APSES domains of Res1 and Res2 (the isolated N-terminal 157 residues of Res1 bind the cdc22 promoter, and that fragment alone rescues a cdc10 null; PMID:7739540), Res1 and Res2 are the DNA-binding subunits of MBF (PMID:18662996, PMID:19714215), and Cdc10 reaches promoters through its C-terminal association with them. GO:0001228 is defined as a DNA-binding transcription factor activity, i.e. the activity of the protein that itself contacts the cis-regulatory sequence, which for MBF is Res1/Res2. The biology (Cdc10 is required for MBF to activate Pol II transcription of the G1/S regulon) is right, but the molecular-function class fits the Res subunits, not the shared Swi6-like subunit; SGD annotates Swi6, the budding-yeast counterpart, to GO:0003713 transcription coactivator activity, and the SWI6 review in this repository makes the same substitution. Proposing GO:0003713 keeps the activation claim at the level Cdc10 executes (it binds the DNA-bound Res1/Res2 transcription factors and is essential for their output); retaining GO:0001228 with a contributes_to qualifier, as PomBase did on the Baum 1997 row, would be an equally acceptable representation. SCHPO/cdc10 GO:0090575 RNA polymerase II transcription regulator complex ARBA:ARBA00028248 ACCEPT general (21-200) 44 SCHPO/cdc12 GO:0015629 actin cytoskeleton ARBA:ARBA00029230 KEEP_AS_NON_CORE general (21-200) 89 SCHPO/cdc12 GO:0031097 medial cortex ARBA:ARBA00049834 ACCEPT specific (1-20) 3 SCHPO/cdc12 GO:1904498 protein localization to mitotic actomyosin contractile ring ARBA:ARBA00090047 KEEP_AS_NON_CORE leaf (0) 0 SCHPO/cdc15 GO:0005543 phospholipid binding ARBA:ARBA00027145 ACCEPT specific (1-20) 19 SCHPO/cdc15 GO:0106006 cytoskeletal protein-membrane anchor activity ARBA:ARBA00091533 ACCEPT leaf (0) 0 SCHPO/cdc15 GO:0120104 mitotic actomyosin contractile ring, proximal layer ARBA:ARBA00089756 ACCEPT leaf (0) 0 SCHPO/cdc15 GO:1903475 mitotic actomyosin contractile ring assembly ARBA:ARBA00088916 ACCEPT specific (1-20) 3 SCHPO/cdc2 GO:0005634 nucleus ARBA:ARBA00026330 ACCEPT very general (>200 descendants) 473 SCHPO/cdc42 GO:0005938 cell cortex ARBA:ARBA00028374 ACCEPT general (21-200) 76 SCHPO/cdc42 GO:0012505 endomembrane system ARBA:ARBA00028953 KEEP_AS_NON_CORE very general (>200 descendants) 357 SCHPO/cdc42 GO:0016020 membrane ARBA:ARBA00028763 MARK_AS_OVER_ANNOTATED very general (>200 descendants) 895 TOO_GENERAL true but uninformative Redundant Redundant generic parent term; the specific plasma membrane / cell tip membrane terms are annotated and preferred. SCHPO/cdc42 GO:0030010 establishment of cell polarity ARBA:ARBA00086232 ACCEPT general (21-200) 34 SCHPO/cdc42 GO:0030427 site of polarized growth ARBA:ARBA00045039 ACCEPT general (21-200) 38 SCHPO/cdc42 GO:0051286 cell tip ARBA:ARBA00089322 ACCEPT specific (1-20) 20 SCHPO/cds1 GO:0005634 nucleus ARBA:ARBA00026330 ACCEPT very general (>200 descendants) 473 SCHPO/cgs1 GO:0006950 response to stress ARBA:ARBA00026300 KEEP_AS_NON_CORE very general (>200 descendants) 590 SCHPO/cis4 GO:0030003 intracellular monoatomic cation homeostasis ARBA:ARBA00028070 MODIFY general (21-200) 75 NEEDS_MORE_SPECIFIC true but uninformative replacement term The experimentally demonstrated ion and process are more precise than broad ion-homeostasis categories. SCHPO/cis4 GO:0098771 inorganic ion homeostasis ARBA:ARBA00028888 MODIFY general (21-200) 79 NEEDS_MORE_SPECIFIC true but uninformative replacement term The experimentally demonstrated ion and process are more precise than broad ion-homeostasis categories. SCHPO/clp1 GO:0000278 mitotic cell cycle ARBA:ARBA00028458 ACCEPT general (21-200) 121 SCHPO/clp1 GO:0004721 phosphoprotein phosphatase activity ARBA:ARBA00027651 ACCEPT general (21-200) 36 SCHPO/clp1 GO:0007096 regulation of exit from mitosis ARBA:ARBA00092142 ACCEPT specific (1-20) 3 SCHPO/clp1 GO:0032954 regulation of cytokinetic process ARBA:ARBA00087459 ACCEPT general (21-200) 33 SCHPO/clp1 GO:0033554 cellular response to stress ARBA:ARBA00028184 KEEP_AS_NON_CORE very general (>200 descendants) 285 SCHPO/clr4 GO:0003677 DNA binding ARBA:ARBA00029224 KEEP_AS_NON_CORE general (21-200) 130 SCHPO/clr4 GO:0003727 single-stranded RNA binding ARBA:ARBA00089173 KEEP_AS_NON_CORE specific (1-20) 10 SCHPO/clr4 GO:0005721 pericentric heterochromatin ARBA:ARBA00086843 ACCEPT specific (1-20) 2 SCHPO/clr4 GO:0030466 silent mating-type cassette heterochromatin formation ARBA:ARBA00087185 ACCEPT specific (1-20) 1 SCHPO/clr4 GO:0031509 subtelomeric heterochromatin formation ARBA:ARBA00085535 ACCEPT leaf (0) 0 SCHPO/clr4 GO:0031934 mating-type region heterochromatin ARBA:ARBA00086601 ACCEPT leaf (0) 0 SCHPO/clr4 GO:0031981 nuclear lumen ARBA:ARBA00026536 KEEP_AS_NON_CORE general (21-200) 139 SCHPO/clr4 GO:0062072 histone H3K9me2/3 reader activity ARBA:ARBA00093727 ACCEPT leaf (0) 0 SCHPO/clr4 GO:0140720 subtelomeric heterochromatin ARBA:ARBA00087570 ACCEPT leaf (0) 0 SCHPO/clr4 GO:0140727 siRNA-mediated pericentric heterochromatin formation ARBA:ARBA00087565 ACCEPT leaf (0) 0 SCHPO/cnp1 GO:0006325 chromatin organization ARBA:ARBA00028060 KEEP_AS_NON_CORE very general (>200 descendants) 290 SCHPO/cps1 GO:0005576 extracellular region ARBA:ARBA00027128 MARK_AS_OVER_ANNOTATED very general (>200 descendants) 276 WRONG_TAXON wrong fungal Native SpCPS has high-throughput support for fungal-type vacuolar localization, and engineered SpCPS fusion proteins traffic through the MVB/vacuolar pathway rather than establishing secretion. The secreted-enzyme evidence comes from mammalian PM20D1, not from fungal Cps1. Although a minor or conditional extracellular pool has not been excluded experimentally, the current electronic assertion lacks direct fungal support. SCHPO/cps1 GO:0006520 amino acid metabolic process ARBA:ARBA00026411 ACCEPT general (21-200) 183 SCHPO/cps1 GO:0006629 lipid metabolic process ARBA:ARBA00028591 MARK_AS_OVER_ANNOTATED very general (>200 descendants) 608 WRONG_TAXON wrong fungal Mammalian PM20D1 catalyzes reversible N-acyl-amino-acid formation/hydrolysis, but that secreted adipocyte enzyme provides only a paralog hypothesis for fungal Cps1. O13968 is closer to fungal CPS proteins than to human PM20D1, its informative domain signatures point to carboxypeptidase S, and no fungal lipid-catalysis assay supports this ARBA-only biological-process annotation. A promiscuous nonpeptide side activity can still be tested, but it should not be asserted as established lipid metabolism. SCHPO/cps1 GO:0016810 hydrolase activity, acting on carbon-nitrogen (but not peptide) bonds ARBA:ARBA00026849 MARK_AS_OVER_ANNOTATED very general (>200 descendants) 269 WRONG_TAXON wrong fungal The mammalian PM20D1 N-acyl-amino-acid hydrolase/synthase activity demonstrates substrate divergence in one M20A paralog, not the activity of fungal Cps1. The fungal lineage, target vacuolar localization, and carboxypeptidase-S signatures support peptide C-terminal hydrolysis; no direct fungal assay establishes nonpeptide N-acyl-amino-acid hydrolysis for O13968. SCHPO/cps1 GO:0043604 obsolete amide biosynthetic process ARBA:ARBA00028836 REMOVE leaf (0) 0 UNSUPPORTED overreach manual UNSUPPORTED Mammalian PM20D1 can condense fatty acids with amino acids, but that reaction has not been shown for fungal Cps1 and should not be propagated from a divergent secreted paralog to O13968. GO:0043604 is also obsolete, and an active product-specific biosynthetic replacement cannot be selected before the target reaction is established. SCHPO/cps1 GO:0043605 obsolete amide catabolic process ARBA:ARBA00047244 MODIFY leaf (0) 0 OTHER_TERM different term needed replacement term Live QuickGO confirms GO:0043605 is obsolete. Peptide bonds are amide bonds, and the supported conserved peptide-hydrolysis role supplies the evidence-backed active replacement. This does not assume that the additional nonpeptide substrate hypothesis is false. SCHPO/cps1 GO:1990845 adaptive thermogenesis ARBA:ARBA00089174 REMOVE specific (1-20) 3 WRONG_TAXON wrong manual WRONG_TAXON PM20D1-dependent uncoupling is a mammalian adipocyte/mitochondrial outcome of a secreted paralog. No evidence places vacuolar fungal Cps1 upstream of a regulated heat-production pathway in S. pombe, so this electronic transfer should be removed rather than retained as a candidate target function. SCHPO/cul1 GO:0000152 nuclear ubiquitin ligase complex ARBA:ARBA00043646 ACCEPT specific (1-20) 8 SCHPO/cul1 GO:0019005 SCF ubiquitin ligase complex ARBA:ARBA00091951 ACCEPT specific (1-20) 18 SCHPO/cul1 GO:0031146 SCF-dependent proteasomal ubiquitin-dependent protein catabolic process ARBA:ARBA00084384 ACCEPT leaf (0) 0 SCHPO/cut1 GO:0000280 nuclear division ARBA:ARBA00028466 MARK_AS_OVER_ANNOTATED general (21-200) 120 TOO_GENERAL true but uninformative general Accurate but overly general; the specific term mitotic sister chromatid separation (GO:0051306) is the informative annotation already present and better reflects the molecular action. SCHPO/cut1 GO:0098813 nuclear chromosome segregation ARBA:ARBA00027947 ACCEPT general (21-200) 80 SCHPO/cut7 GO:0000073 initial mitotic spindle pole body separation ARBA:ARBA00090202 ACCEPT leaf (0) 0 SCHPO/cut7 GO:0015630 microtubule cytoskeleton ARBA:ARBA00029268 KEEP_AS_NON_CORE general (21-200) 108 SCHPO/cut9 GO:0005680 anaphase-promoting complex ARBA:ARBA00043276 ACCEPT leaf (0) 0 SCHPO/dcr1 GO:0010467 gene expression ARBA:ARBA00028330 MARK_AS_OVER_ANNOTATED very general (>200 descendants) 724 TOO_GENERAL true but uninformative general Too general to be useful; the gene's role is in gene silencing, captured by more specific terms. SCHPO/dcr1 GO:0031047 regulatory ncRNA-mediated gene silencing ARBA:ARBA00027536 ACCEPT general (21-200) 51 SCHPO/ecm31 GO:0072330 monocarboxylic acid biosynthetic process ARBA:ARBA00027175 MODIFY general (21-200) 95 NEEDS_MORE_SPECIFIC true but uninformative replacement term Too general; pantothenate biosynthetic process (a child term) is the informative annotation, as in the S. cerevisiae ECM31 review. SCHPO/hsp104 GO:0006457 protein folding ARBA:ARBA00027200 MODIFY specific (1-20) 7 NEEDS_MORE_SPECIFIC true but uninformative replacement term Hsp104 dissolves preformed protein aggregates and returns clients to the folding pathway; it is not a general nascent-chain folding chaperone. SCHPO/hsp104 GO:0034605 cellular response to heat ARBA:ARBA00026567 ACCEPT specific (1-20) 3 SCHPO/hsp104 GO:0043335 protein unfolding ARBA:ARBA00086271 ACCEPT leaf (0) 0 SCHPO/hsp78 GO:0006457 protein folding ARBA:ARBA00027200 MODIFY specific (1-20) 7 NEEDS_MORE_SPECIFIC true but uninformative replacement term Fungal Hsp78 acts after mitochondrial matrix proteins have misfolded and aggregated. The Hsp78 PAINT node already carries the better descendant process, GO:0042026 protein refolding. SCHPO/hsp78 GO:0034605 cellular response to heat ARBA:ARBA00026567 ACCEPT specific (1-20) 3 SCHPO/hsp78 GO:0043335 protein unfolding ARBA:ARBA00086271 ACCEPT leaf (0) 0 SCHPO/lsm6 GO:0005634 nucleus ARBA:ARBA00026330 ACCEPT very general (>200 descendants) 473 SCHPO/lsm6 GO:0120114 Sm-like protein family complex ARBA:ARBA00027169 ACCEPT general (21-200) 29 SCHPO/mad2 GO:0007094 mitotic spindle assembly checkpoint signaling ARBA:ARBA00044419 ACCEPT leaf (0) 0 SCHPO/mad2 GO:0033597 mitotic checkpoint complex ARBA:ARBA00085107 ACCEPT specific (1-20) 1 SCHPO/mad3 GO:0032991 protein-containing complex ARBA:ARBA00028902 MODIFY very general (>200 descendants) 2083 NEEDS_MORE_SPECIFIC true but uninformative replacement term The root term is uninformative. The complex Mad3 belongs to is the mitotic checkpoint complex (Mad3-Mad2-Slp1), established by co-immunoprecipitation, APC/C co-purification and a crystal structure (PMID:11909965, PMID:18556659, PMID:22437499) and already annotated as GO:0033597 by IDA/IPI; the same resolution was applied to the budding-yeast MAD3 review. SCHPO/mcs6 GO:0004693 cyclin-dependent protein serine/threonine kinase activity ARBA:ARBA00043522 ACCEPT leaf (0) 0 SCHPO/mcs6 GO:0032968 positive regulation of transcription elongation by RNA polymerase II ARBA:ARBA00033872 ACCEPT leaf (0) 0 SCHPO/met16 GO:0006790 sulfur compound metabolic process ARBA:ARBA00028021 MODIFY general (21-200) 190 NEEDS_MORE_SPECIFIC true but uninformative replacement term ARBA rule-based IEA to the general parent 'sulfur compound metabolic process'. True, but the informative process is sulfate assimilation (GO:0000103), which GOA lacks for met16 and which the PomBase GO-CAM uses as part_of for its activity. Refine. SCHPO/mph1 GO:0007094 mitotic spindle assembly checkpoint signaling ARBA:ARBA00044419 ACCEPT leaf (0) 0 SCHPO/mph1 GO:0098813 nuclear chromosome segregation ARBA:ARBA00027947 KEEP_AS_NON_CORE general (21-200) 80 SCHPO/mst1 GO:0120261 regulation of heterochromatin organization ARBA:ARBA00095329 MODIFY specific (1-20) 18 NEEDS_MORE_SPECIFIC true but uninformative replacement term This ARBA process transfer is broader and less informative than the direct H3K4ac/positive heterochromatin-formation annotation, but it captures a demonstrated S. pombe role of Mst1 in pericentric heterochromatin reassembly and should be replaced by the polarity-bearing PomBase child term. SCHPO/mst2 GO:0031507 heterochromatin formation ARBA:ARBA00033536 MODIFY general (21-200) 25 OTHER_TERM different term needed replacement term Later direct evidence resolves the sign of this ARBA prediction. Mst2-mediated H3K14 acetylation counteracts the H3K14ub-H3K9me3 feedback loop and restrains heterochromatin spreading, so the replacement should name negative regulation of heterochromatin organization. SCHPO/mst2 GO:0070775 H3 histone acetyltransferase complex ARBA:ARBA00084418 MODIFY specific (1-20) 7 NEEDS_MORE_SPECIFIC true but uninformative replacement term The ARBA prediction is directionally correct but too general. Mst2 is the catalytic subunit of the named Mst2 histone acetyltransferase complex that is already present in PomBase. SCHPO/mst2 GO:0120261 regulation of heterochromatin organization ARBA:ARBA00095329 ACCEPT specific (1-20) 18 SCHPO/mus81 GO:0000712 resolution of meiotic recombination intermediates ARBA:ARBA00090877 ACCEPT leaf (0) 0 SCHPO/mus81 GO:0000724 double-strand break repair via homologous recombination ARBA:ARBA00027336 ACCEPT specific (1-20) 14 SCHPO/mus81 GO:0031297 replication fork processing ARBA:ARBA00086530 ACCEPT specific (1-20) 4 SCHPO/mus81 GO:0043596 nuclear replication fork ARBA:ARBA00026835 KEEP_AS_NON_CORE specific (1-20) 7 SCHPO/mus81 GO:0048476 Holliday junction resolvase complex ARBA:ARBA00091587 ACCEPT leaf (0) 0 SCHPO/nip7 GO:1902626 assembly of large subunit precursor of preribosome ARBA:ARBA00092444 ACCEPT leaf (0) 0 SCHPO/nuc2 GO:0005680 anaphase-promoting complex ARBA:ARBA00043276 ACCEPT leaf (0) 0 SCHPO/pab1 GO:0010972 negative regulation of G2/M transition of mitotic cell cycle ARBA:ARBA00084549 ACCEPT specific (1-20) 5 SCHPO/pab1 GO:1902531 regulation of intracellular signal transduction ARBA:ARBA00027126 MODIFY very general (>200 descendants) 278 NEEDS_MORE_SPECIFIC true but uninformative replacement term Not wrong, but far too shallow to be informative: the intracellular signalling pathways that PP2A-B55(Pab1) is experimentally shown to regulate are specific and directional, namely negative regulation of TORC2 signalling (direct dephosphorylation of Gad8 Ser546; Martin et al. 2017) and negative regulation of septation initiation signalling (suppression of etd1, mob1, sid1 and cdc11 mutants; Lahoz et al. 2010). Replace the generic term with those two descendants, both of which are already carried by experimental rows. SCHPO/pap1 GO:0000978 RNA polymerase II cis-regulatory region sequence-specific DNA binding ARBA:ARBA00028975 ACCEPT specific (1-20) 12 SCHPO/pap1 GO:0000981 DNA-binding transcription factor activity, RNA polymerase II-specific ARBA:ARBA00029016 ACCEPT specific (1-20) 8 SCHPO/pap1 GO:0034599 cellular response to oxidative stress ARBA:ARBA00027632 ACCEPT general (21-200) 25 SCHPO/pli1 GO:0005694 chromosome ARBA:ARBA00026361 ACCEPT very general (>200 descendants) 204 SCHPO/pli1 GO:0007059 chromosome segregation ARBA:ARBA00026830 KEEP_AS_NON_CORE general (21-200) 86 SCHPO/pli1 GO:0019789 SUMO transferase activity ARBA:ARBA00027358 ACCEPT specific (1-20) 3 SCHPO/pli1 GO:0097240 chromosome attachment to the nuclear envelope ARBA:ARBA00089802 KEEP_AS_NON_CORE specific (1-20) 6 SCHPO/pop1 GO:1990756 ubiquitin-like ligase-substrate adaptor activity ARBA:ARBA00047228 ACCEPT leaf (0) 0 SCHPO/pop2 GO:1990756 ubiquitin-like ligase-substrate adaptor activity ARBA:ARBA00047228 ACCEPT leaf (0) 0 SCHPO/ppa2 GO:0004721 phosphoprotein phosphatase activity ARBA:ARBA00027651 MODIFY general (21-200) 36 NEEDS_MORE_SPECIFIC true but uninformative replacement term The parent term is true of Ppa2 (EC 3.1.3.16 PPP-family metallophosphatase with direct enzymatic and genetic evidence), but the ARBA rule could just as well have mapped to the specific child, which is what the UniProt catalytic-activity annotations of P23636 (Rhea phosphoserine/phosphothreonine hydrolysis) and the in vitro Rec8 dephosphorylation data support. Modify to GO:0004722 for consistency with the IMP row from PMID:2170029, which is treated the same way. SCHPO/ppc1 GO:0004632 phosphopantothenate--cysteine ligase activity ARBA:ARBA00088314 ACCEPT leaf (0) 0 SCHPO/ppc1 GO:0015937 coenzyme A biosynthetic process ARBA:ARBA00026783 ACCEPT leaf (0) 0 SCHPO/ppk18 GO:1901992 positive regulation of mitotic cell cycle phase transition ARBA:ARBA00029089 ACCEPT specific (1-20) 8 SCHPO/puc1 GO:0016538 cyclin-dependent protein serine/threonine kinase regulator activity ARBA:ARBA00027788 MODIFY specific (1-20) 2 NEEDS_MORE_SPECIFIC true but uninformative replacement term The automated inference stops at the generic parent; the experimental evidence (Puc1-associated Cdc2 kinase activity toward histone H1 and Rum1, complementation of CLN loss) shows that Puc1 activates Cdc2, so the activator child term (GO:0061575) proposed on the IBA and IGI rows is the consistent replacement. SCHPO/puc1 GO:0044843 cell cycle G1/S phase transition ARBA:ARBA00026661 ACCEPT specific (1-20) 1 SCHPO/puc1 GO:0051726 regulation of cell cycle ARBA:ARBA00029144 MODIFY very general (>200 descendants) 377 NEEDS_MORE_SPECIFIC true but uninformative replacement term The mapping is correct but uninformative; the specific process is positive regulation of the G1/S transition of the mitotic cell cycle (GO:1900087), supported by the EXP row (PMID:9201720), the complementation of cln-deficient budding yeast (PMID:1828291) and the Rum1-directed kinase activity of Puc1-Cdc2 (Martin-Castellanos et al. 2000). SCHPO/rad3 GO:0004672 protein kinase activity ARBA:ARBA00027018 MODIFY general (21-200) 115 NEEDS_MORE_SPECIFIC true but uninformative replacement term Rad3 is specifically a protein Ser/Thr kinase; the more specific term is supported by experimental data, so this general term should be refined. SCHPO/rad3 GO:0035556 intracellular signal transduction ARBA:ARBA00026887 KEEP_AS_NON_CORE general (21-200) 195 SCHPO/rad3 GO:0000785 chromatin ARBA:ARBA00027601 ACCEPT general (21-200) 86 SCHPO/rbx1 GO:0010498 proteasomal protein catabolic process ARBA:ARBA00028386 ACCEPT general (21-200) 21 SCHPO/res1 GO:0001228 DNA-binding transcription activator activity, RNA polymerase II-specific ARBA:ARBA00027759 ACCEPT leaf (0) 0 SCHPO/res1 GO:0030907 MBF transcription complex ARBA:ARBA00088331 ACCEPT leaf (0) 0 SCHPO/res2 GO:0001228 DNA-binding transcription activator activity, RNA polymerase II-specific ARBA:ARBA00027759 ACCEPT leaf (0) 0 SCHPO/res2 GO:0090575 RNA polymerase II transcription regulator complex ARBA:ARBA00028248 ACCEPT general (21-200) 44 SCHPO/rfc3 GO:0031391 Elg1 RFC-like complex ARBA:ARBA00028328 ACCEPT leaf (0) 0 SCHPO/rfc3 GO:0070914 UV-damage excision repair ARBA:ARBA00028029 ACCEPT specific (1-20) 1 SCHPO/rfc3 GO:1902983 DNA strand elongation involved in mitotic DNA replication ARBA:ARBA00090648 ACCEPT specific (1-20) 2 SCHPO/rhp51 GO:0000723 telomere maintenance ARBA:ARBA00027335 KEEP_AS_NON_CORE specific (1-20) 18 SCHPO/rhp51 GO:0006312 mitotic recombination ARBA:ARBA00028023 ACCEPT specific (1-20) 4 SCHPO/rhp51 GO:0007131 reciprocal meiotic recombination ARBA:ARBA00028998 KEEP_AS_NON_CORE specific (1-20) 14 SCHPO/rhp51 GO:0042148 DNA strand invasion ARBA:ARBA00085980 ACCEPT specific (1-20) 2 SCHPO/rhp51 GO:0042802 identical protein binding ARBA:ARBA00027930 ACCEPT specific (1-20) 1 SCHPO/rpo41 GO:0006390 mitochondrial transcription ARBA:ARBA00086224 ACCEPT specific (1-20) 4 SCHPO/rpo41 GO:0034245 mitochondrial DNA-directed RNA polymerase complex ARBA:ARBA00090620 ACCEPT leaf (0) 0 SCHPO/rqh1 GO:0000724 double-strand break repair via homologous recombination ARBA:ARBA00027336 ACCEPT specific (1-20) 14 SCHPO/rqh1 GO:0000729 DNA double-strand break processing ARBA:ARBA00090881 ACCEPT specific (1-20) 4 SCHPO/rqh1 GO:0003677 DNA binding ARBA:ARBA00029224 ACCEPT general (21-200) 130 SCHPO/rqh1 GO:0006312 mitotic recombination ARBA:ARBA00028023 KEEP_AS_NON_CORE specific (1-20) 4 SCHPO/rqh1 GO:0031422 RecQ family helicase-topoisomerase III complex ARBA:ARBA00085865 ACCEPT leaf (0) 0 SCHPO/rqh1 GO:0031573 mitotic intra-S DNA damage checkpoint signaling ARBA:ARBA00085562 ACCEPT leaf (0) 0 SCHPO/sad1 GO:0005635 nuclear envelope ARBA:ARBA00026328 ACCEPT general (21-200) 29 SCHPO/sgo1 GO:0000779 condensed chromosome, centromeric region ARBA:ARBA00027570 ACCEPT specific (1-20) 12 SCHPO/sid2 GO:0010564 regulation of cell cycle process ARBA:ARBA00027431 KEEP_AS_NON_CORE very general (>200 descendants) 338 SCHPO/sid2 GO:0035974 meiotic spindle pole body ARBA:ARBA00095381 ACCEPT leaf (0) 0 SCHPO/sir1 GO:0000103 sulfate assimilation ARBA:ARBA00033980 ACCEPT specific (1-20) 1 SCHPO/slp1 GO:0031145 anaphase-promoting complex-dependent catabolic process ARBA:ARBA00034936 ACCEPT leaf (0) 0 SCHPO/spa2 GO:0030427 site of polarized growth ARBA:ARBA00045039 ACCEPT general (21-200) 38 SCHPO/spg1 GO:0005816 spindle pole body ARBA:ARBA00029126 ACCEPT specific (1-20) 18 SCHPO/spg1 GO:0035556 intracellular signal transduction ARBA:ARBA00026887 ACCEPT general (21-200) 195 SCHPO/spg1 GO:0090068 positive regulation of cell cycle process ARBA:ARBA00029176 ACCEPT general (21-200) 104 SCHPO/spm1 GO:0006950 response to stress ARBA:ARBA00026300 MODIFY very general (>200 descendants) 590 NEEDS_MORE_SPECIFIC true but uninformative replacement term GO:0006950 is over-general, while spm1 disruption and Spm1 activation assays specifically place the kinase in responses to high osmolarity and elevated temperature. SCHPO/spt16 GO:0010468 regulation of gene expression ARBA:ARBA00028334 KEEP_AS_NON_CORE very general (>200 descendants) 874 SCHPO/spt16 GO:0034728 nucleosome organization ARBA:ARBA00085234 ACCEPT specific (1-20) 2 SCHPO/ste9 GO:0031145 anaphase-promoting complex-dependent catabolic process ARBA:ARBA00034936 ACCEPT leaf (0) 0 SCHPO/sua1 GO:0006790 sulfur compound metabolic process ARBA:ARBA00028021 ACCEPT general (21-200) 190 SCHPO/swi6 GO:0000792 heterochromatin ARBA:ARBA00027530 ACCEPT specific (1-20) 14 SCHPO/swi6 GO:0040029 epigenetic regulation of gene expression ARBA:ARBA00033485 KEEP_AS_NON_CORE general (21-200) 44 SCHPO/thi20 GO:0042364 water-soluble vitamin biosynthetic process ARBA:ARBA00029043 MODIFY specific (1-20) 19 NEEDS_MORE_SPECIFIC true but uninformative replacement term Replace the grouping term with the specific process, as done for the thiamine metabolic process rows in the S. cerevisiae THI20/THI21 reviews. SCHPO/tim10 GO:0045039 protein insertion into mitochondrial inner membrane ARBA:ARBA00029129 ACCEPT specific (1-20) 2 SCHPO/tnr3 GO:0042723 thiamine-containing compound metabolic process ARBA:ARBA00028583 MODIFY specific (1-20) 12 NEEDS_MORE_SPECIFIC true but uninformative replacement term Use the specific process. SCHPO/tnr3 GO:0044715 8-oxo-dGDP phosphatase activity ARBA:ARBA00085858 KEEP_AS_NON_CORE leaf (0) 0 SCHPO/tpx1 GO:0034599 cellular response to oxidative stress ARBA:ARBA00027632 ACCEPT general (21-200) 25 SCHPO/trm402 GO:0030488 tRNA methylation ARBA:ARBA00028068 ACCEPT specific (1-20) 16 SCHPO/trx1 GO:0045454 cell redox homeostasis ARBA:ARBA00085337 ACCEPT leaf (0) 0 SCHPO/ulp2 GO:0019783 ubiquitin-like protein peptidase activity ARBA:ARBA00027361 MODIFY specific (1-20) 19 NEEDS_MORE_SPECIFIC true but uninformative replacement term The broad proteolysis/peptidase assertion is correct, but direct biochemical experiments establish SUMO deconjugation by a cysteine protease. Use deSUMOylase activity to preserve modifier specificity; ubiquitin-like does not mean ubiquitin itself is the substrate. SCHPO/ura7 GO:0097268 cytoophidium ARBA:ARBA00089783 ACCEPT leaf (0) 0 SCHPO/vas2 GO:0010496 intercellular transport ARBA:ARBA00092758 REMOVE specific (1-20) 3 TERM_MISREAD wrong manual TERM_MISREAD GO:0010496 means movement between cells, as verified in QuickGO. The experimentally established Vas2/AP-1 pathway sorts cargo between compartments inside a cell. This ARBA assertion conflates intercellular and intracellular transport and lacks an independent intercellular mechanism. SCHPO/wis1 GO:0005737 cytoplasm ARBA:ARBA00026971 ACCEPT very general (>200 descendants) 1146 SCHPO/wis1 GO:0032991 protein-containing complex ARBA:ARBA00028902 MARK_AS_OVER_ANNOTATED very general (>200 descendants) 2083 TOO_GENERAL true but uninformative Generic Generic complex term superseded by the specific Mcs4 RR-MAPKKK complex annotation. SCHPO/wis1 GO:0038066 p38MAPK cascade ARBA:ARBA00088051 ACCEPT leaf (0) 0 SCHPO/wis1 GO:0071470 cellular response to osmotic stress ARBA:ARBA00027118 ACCEPT specific (1-20) 19 SOLLC/PG2 GO:0009830 cell wall modification involved in abscission ARBA:ARBA00084907 MODIFY leaf (0) 0 TOO_SPECIFIC overreach replacement term "PG2 does modify/disassemble the cell wall, but it does so during fruit RIPENING, not in abscission. The annotation is a family-level ARBA over-generalization: the GH28 polygalacturonase family includes abscission-zone PGs (a distinct paralogous role), and the rule has been applied to PG2 by sequence similarity rather than evidence. PG2 is expressed essentially only in ripening fruit, and there is no evidence for a PG2 abscission function. The genuine, gene-specific biology (apoplastic pectin degradation driving cell-wall disassembly in the softening pericarp) is better captured by the more general, context-neutral ""plant-type cell wall organization"" (GO:0009664), which explicitly covers disassembly of the pectin-containing wall. Modify to that term rather than retaining the incorrect abscission context." SOLLC/PG2 GO:0009901 anther dehiscence ARBA:ARBA00084450 REMOVE leaf (0) 0 WRONG_PARALOG wrong manual WRONG_PARALOG "This is a family-level ARBA over-annotation. Anther dehiscence (GO:0009901, ""the dehiscence of an anther to release the pollen grains"") is mediated in other species by anther/pollen-specific polygalacturonases (e.g. Arabidopsis QRT/ADPG paralogs), not by the tomato fruit PG2. Tomato PG2 is expressed essentially only in ripening fruit at the protein level [PMID:2152163], and neither the primary literature nor the deep-research synthesis provides any evidence of a role in anther dehiscence (the term ""dehiscence"" does not appear anywhere in the research corpus). The annotation reflects sequence similarity to a distinct paralogous subfamily and should be removed." SOLLC/PG2 GO:0010047 fruit dehiscence ARBA:ARBA00091347 REMOVE leaf (0) 0 WRONG_PARALOG wrong manual WRONG_PARALOG "Another family-level ARBA over-annotation that is biologically inapplicable to tomato. Fruit dehiscence (GO:0010047, ""the spontaneous opening of the fruit permitting the escape of seeds"") is a property of dry dehiscent fruits (e.g. Arabidopsis siliques, legume pods) and is mediated by dehiscence-zone polygalacturonases. The tomato fruit is a fleshy indehiscent berry, and PG2's documented role is pectin depolymerization and softening during ripening [PMID:7827495], not seed-release pod shatter. There is no evidence (literature or deep research) for a PG2 dehiscence function. The annotation is an incorrect cross-paralog transfer and should be removed." SOLLC/PR1B1 GO:0098542 defense response to other organism ARBA:ARBA00027395 ACCEPT general (21-200) 77 SOLTU/CCOAOMT GO:0007623 circadian rhythm ARBA:ARBA00027901 REMOVE specific (1-20) 19 UNSUPPORTED overreach manual UNSUPPORTED "This is an over-prediction from an automated ARBA model and is not supported by any of the curated CCoAOMT literature. The well-supported function of the protein is caffeoyl-CoA O-methylation feeding lignin/suberin precursor pools - a phenylpropanoid-pathway role with no established connection to the circadian clock. While transcript abundance of phenylpropanoid genes can oscillate diurnally, expression rhythmicity is not equivalent to a molecular ""involvement in"" circadian rhythm, and the deep-research report - which surveys the potato and Solanaceae CCoAOMT literature for function, localization and pathway placement - describes the enzyme purely as a phenylpropanoid/lignin/suberin methyltransferase. With no supporting evidence, the ARBA ""circadian rhythm"" term should be removed as a spurious over-annotation." SOLTU/PATB1 GO:0016298 lipase activity ARBA:ARBA00027300 MODIFY general (21-200) 37 NEEDS_MORE_SPECIFIC true but uninformative replacement term "The core molecular function of patatin is well documented as a lipid acyl hydrolase (LAH) with phospholipase A-like behaviour: it hydrolyzes glycerophospholipids (mono- and diacylphospholipids) as well as galactolipids and neutral glycerolipids, acting at the sn-1 and sn-2 acyl positions in a Ca2+-independent manner via a Ser-Asp catalytic dyad. UniProt's IBA annotations for this protein already include ""phospholipase activity"" (GO:0004620). The generic ""lipase activity"" should be MODIFIED to the more informative ""glycerophospholipase activity"" (GO:0004620), which captures the documented phospholipid-deacylation function while remaining defensible given that PATB1-specific positional specificity (PLA1 vs PLA2) and kinetics are not uniquely resolved. (Note: PATB1 also acts on neutral and galacto-lipids, so the broad LAH character is real; ""glycerophospholipase activity"" is chosen as the most specific single MF strongly supported by both the family biochemistry and the existing IBA call.)" STRCO/actI-ORF1 GO:0030497 fatty acid elongation ARBA:ARBA00028259 REMOVE specific (1-20) 4 WRONG_PROCESS wrong manual WRONG_PROCESS Wrong-specific fatty-acid term that mischaracterizes polyketide chain extension; redundant once the actinorhodin/polyketide terms are applied. STRCO/actI-ORF2 GO:0016747 acyltransferase activity, transferring groups other than amino-acyl groups ARBA:ARBA00027717 MARK_AS_OVER_ANNOTATED very general (>200 descendants) 345 UNCLASSIFIED unclassified CLF has no active site; this catalytic MF over-annotates the subunit. Better represented as contributes_to / annotation to the KS-CLF complex. STRPU/Alx1 GO:0048513 animal organ development ARBA:ARBA00029247 MARK_AS_OVER_ANNOTATED very general (>200 descendants) 1888 TOO_GENERAL true but uninformative general Vertebrate-derived generalization; the specific processes (mesodermal cell fate specification, regulation of biomineral tissue development) are proposed as NEW and capture the actual biology. STRPU/Alx1 GO:1990837 sequence-specific double-stranded DNA binding ARBA:ARBA00028376 ACCEPT general (21-200) 48 STRPU/Delta GO:0000902 cell morphogenesis ARBA:ARBA00028811 REMOVE general (21-200) 157 TOO_GENERAL true but uninformative manual TOO_GENERAL Uninformative and unsupported for this gene; the specific processes Delta participates in (Notch signaling pathway, mesodermal cell fate specification, negative regulation of neurogenesis) are captured by other rows. STRPU/Delta GO:0005886 plasma membrane ARBA:ARBA00027801 ACCEPT very general (>200 descendants) 415 STRPU/Delta GO:0042063 gliogenesis ARBA:ARBA00086246 REMOVE general (21-200) 83 UNSUPPORTED overreach manual UNSUPPORTED Over-propagated machine-learning transfer with no organism-appropriate evidence; the neural role that is documented for sea urchin Delta is lateral inhibition of neural progenitors, captured under negative regulation of neurogenesis. STRPU/Delta GO:0048666 neuron development ARBA:ARBA00028378 MODIFY general (21-200) 186 OTHER_TERM different term needed replacement term The gene product is the ligand of a signal that limits neurogenesis, so the appropriate term is a regulation term (GO:0050768 negative regulation of neurogenesis, proposed as a NEW row), not the direct neuron development term. This is a secondary, non-core role relative to the endomesoderm signaling function. THLAR/FAE1 GO:0005783 endoplasmic reticulum ARBA:ARBA00028672 ACCEPT general (21-200) 100 THLAR/TFP GO:0019760 glucosinolate metabolic process ARBA:ARBA00043526 MODIFY specific (1-20) 6 NEEDS_MORE_SPECIFIC true but uninformative replacement term Correct, but the generic metabolic-process parent should be specialized to the catabolic child, consistent with the experimentally supported breakdown role of TaTFP downstream of myrosinase. THLAR/matK GO:0005737 cytoplasm ARBA:ARBA00026971 MODIFY very general (>200 descendants) 1146 NEEDS_MORE_SPECIFIC true but uninformative replacement term Over-general and redundant. MatK is a plastid genome-encoded protein that localizes to the chloroplast stroma (soluble fraction in transplastomic tobacco); the generic cytoplasm term should be specialized to the chloroplast stroma, consistent with the separate chloroplast annotation. VIBCH/cds1 GO:1901605 alpha-amino acid metabolic process ARBA:ARBA00026968 ACCEPT leaf (0) 0 WHEAT/A0A3B6GK97 GO:0016787 hydrolase activity ARBA:ARBA00026276 MODIFY very general (>200 descendants) 1283 NEEDS_MORE_SPECIFIC true but uninformative replacement term "The patatin/PNPLA domain is a lipid acyl hydrolase module that cleaves carboxylic ester bonds of glycerolipids using a Ser-Asp catalytic dyad [PMID:12779324]. ""Hydrolase activity"" (GO:0016787) is therefore correct but far too general; a more informative and equally well-supported term is ""carboxylic ester hydrolase activity"" (GO:0052689), the parent of the lipase/phospholipase/acylglycerol-lipase activities characteristic of this family. The UniProt entry's own family-level FUNCTION text describes non-specific lipolytic acyl hydrolase activity hydrolyzing phospholipids and galactolipids. More substrate-specific functions are in fact asserted for this protein by GO_Central as IBA (phylogenetic) annotations - glycerophospholipase activity (GO:0004620) and monoacylglycerol lipase activity (GO:0047372) - which are visible in AmiGO/GOlr but were not returned by the QuickGO GOA pull that seeded this review (see reference GO_REF:0000033 and the AmiGO record at http://amigo.geneontology.org/amigo/gene_product/UniProtKB:A0A3B6GK97). Because those IBA lipase terms already capture the specific activity out of band, this generic ARBA ""hydrolase activity"" annotation is best modified to their immediate informative parent, ""carboxylic ester hydrolase activity"" (GO:0052689), rather than left at the root-level hydrolase term or duplicated into the specific IBA terms. IMPORTANT CAVEAT - the family-level MF may not hold for this specific deposited sequence. A reproducible bioinformatics analysis (file:WHEAT/A0A3B6GK97/A0A3B6GK97-bioinformatics/RESULTS.md) shows that the modeled 302-aa protein places in the pPLAII subfamily but LACKS the entire N-terminal half of the patatin catalytic domain - both the oxyanion glycine-rich block (DGGG) and the catalytic-serine nucleophile elbow (G-T-S-T-G) are absent (the sequence has no G-x-S-x-G motif at all), although it retains the catalytic Asp. As modeled it is therefore predicted catalytically INACTIVE (no nucleophile), most likely reflecting an incomplete/incorrect gene model (~100-130 aa shorter than orthologs) rather than - but not excluding - a genuine degenerate pseudo-enzyme. The IBA lipase calls were propagated phylogenetically and do not verify active-site integrity. The MODIFY to carboxylic ester hydrolase activity is retained as the correct FAMILY-level term, but with this explicit caveat that the activity is not verifiable on, and may be absent from, the current sequence model." WHEAT/F6LAX4 GO:0005634 nucleus ARBA:ARBA00026330 ACCEPT very general (>200 descendants) 473 WHEAT/F6LAX4 GO:0005737 cytoplasm ARBA:ARBA00026971 MODIFY very general (>200 descendants) 1146 NEEDS_MORE_SPECIFIC true but uninformative replacement term Cytoplasm (GO:0005737) is correct but more general than warranted. The UniProt entry's GO cross-references for this protein include an explicit GO:0005829 cytosol annotation with IBA:GO_Central evidence (present in the F6LAX4 UniProt record but dropped from the fetched GOA snapshot, which retained only the ARBA IEA cytoplasm term). Cytosol is the appropriate specific compartment for a soluble PP2A scaffold/holoenzyme, and the deep research notes that PP2A catalytic subunits are predominantly cytosolic. Modifying the general cytoplasm IEA to the GO_Central-supported cytosol increases specificity without loss of accuracy. WHEAT/F6LAX4 GO:0032991 protein-containing complex ARBA:ARBA00028902 MARK_AS_OVER_ANNOTATED very general (>200 descendants) 2083 TOO_GENERAL true but uninformative high-level GO:0032991 protein-containing complex is a high-level grouping term that conveys no specific functional information beyond what GO:0000159 (protein phosphatase type 2A complex) already states. Because the more-specific PP2A complex term is present and accepted, this generic complex annotation is an over-annotation and should be flagged as such. XENNA/D3VIU4 GO:0030288 outer membrane-bounded periplasmic space ARBA:ARBA00026684 ACCEPT leaf (0) 0 XENTR/F6WPT1 GO:1903292 protein localization to Golgi membrane ARBA:ARBA00090371 ACCEPT leaf (0) 0 human/A1CF GO:0030895 apolipoprotein B mRNA editing enzyme complex ARBA:ARBA00088257 ACCEPT leaf (0) 0 human/A1CF GO:0140767 enzyme-substrate adaptor activity ARBA:ARBA00047246 ACCEPT specific (1-20) 2 human/A1CF GO:1902373 negative regulation of mRNA catabolic process ARBA:ARBA00089345 MODIFY specific (1-20) 10 NEEDS_MORE_SPECIFIC true but uninformative replacement term The automated process is too broad; the experiments support the specific NMD-regulatory term. human/A2M GO:0004857 enzyme inhibitor activity ARBA:ARBA00026999 KEEP_AS_NON_CORE general (21-200) 60 human/A4GALT GO:0016758 hexosyltransferase activity ARBA:ARBA00026306 MODIFY very general (>200 descendants) 337 NEEDS_MORE_SPECIFIC true but uninformative replacement term Use GO:0035250 to specify transfer of galactose from UDP-galactose while retaining the enzyme's experimentally demonstrated acceptor breadth. The lactosylceramide-specific reaction is already represented separately by GO:0050512. human/A4GNT GO:0008194 UDP-glycosyltransferase activity ARBA:ARBA00028346 MODIFY general (21-200) 195 NEEDS_MORE_SPECIFIC true but uninformative replacement term Replace the definitionally mismatched broad parent with GO:0008375, which correctly specifies transfer of an N-acetylglucosaminyl residue from UDP-GlcNAc to a sugar acceptor and matches the demonstrated A4GNT chemistry. human/A4GNT GO:0016758 hexosyltransferase activity ARBA:ARBA00026306 MODIFY very general (>200 descendants) 337 NEEDS_MORE_SPECIFIC true but uninformative replacement term GO:0008375 records the transferred GlcNAc residue and UDP-GlcNAc donor class and is therefore substantially more informative than GO:0016758. human/AADACL2 GO:0003824 catalytic activity ARBA:ARBA00027533 MODIFY very general (>200 descendants) 6405 NEEDS_MORE_SPECIFIC true but uninformative replacement term A root-adjacent term, fully redundant with GO:0052689 carboxylic ester hydrolase activity already present on this record from the family-specific IPR017157 signature, which is the term the three general molecular-function rows on this protein should all collapse onto. GO:0017171 serine hydrolase activity is also satisfied residue for residue by this protein - an annotated Ser189-Asp341-His371 triad with an HGG oxyanion hole and a GDSSG nucleophile elbow - but it is not carried by any existing row and is pursued instead as a PAINT node-placement recommendation, so GO:0052689 is the replacement proposed here, matching the treatment given to AADACL3 and AADACL4. human/AADAT GO:0005759 mitochondrial matrix ARBA:ARBA00028628 ACCEPT specific (1-20) 17 human/AANAT GO:0008080 N-acetyltransferase activity ARBA:ARBA00029116 MARK_AS_OVER_ANNOTATED general (21-200) 53 TOO_GENERAL true but uninformative parent ARBA machine-learning IEA to the parent term N-acetyltransferase activity. This is correct but less precise than the specific, experimentally supported child term aralkylamine N-acetyltransferase activity (GO:0004059). Marked as over-annotated in favor of the more informative specific term. human/ABCA1 GO:0015850 organic hydroxy compound transport ARBA:ARBA00027649 MODIFY general (21-200) 158 NEEDS_MORE_SPECIFIC true but uninformative replacement term Generic parent; cholesterol is the specific cargo. human/ABCA1 GO:0045332 phospholipid translocation ARBA:ARBA00026752 ACCEPT specific (1-20) 12 human/ABCA3 GO:0005737 cytoplasm ARBA:ARBA00026971 MODIFY very general (>200 descendants) 1146 NEEDS_MORE_SPECIFIC true but uninformative replacement term The inferred broad cellular compartment is compatible with ABCA3, but human immunoelectron microscopy localizes the protein to the limiting membrane of lamellar bodies (PMID:11718719; PMID:11940594). Refine this compatible broad location to the directly demonstrated functional membrane compartment; the original broad location is not contradicted. human/ABCA3 GO:0006869 lipid transport ARBA:ARBA00027046 ACCEPT general (21-200) 174 human/ABCA3 GO:0012505 endomembrane system ARBA:ARBA00028953 MODIFY very general (>200 descendants) 357 NEEDS_MORE_SPECIFIC true but uninformative replacement term The inferred broad cellular compartment is compatible with ABCA3, but human immunoelectron microscopy localizes the protein to the limiting membrane of lamellar bodies (PMID:11718719; PMID:11940594). Refine this compatible broad location to the directly demonstrated functional membrane compartment; the original broad location is not contradicted. human/ABCA4 GO:0015850 organic hydroxy compound transport ARBA:ARBA00027649 MODIFY general (21-200) 158 OTHER_TERM different term needed replacement term The live GO definitions specify an organic alcohol or retinol. Direct transport assays found no ATP-dependent all-trans-retinol transfer. Replace this with phospholipid translocation; retinal reduction to retinol is performed downstream by RDH enzymes. human/ABCA4 GO:0045332 phospholipid translocation ARBA:ARBA00026752 ACCEPT specific (1-20) 12 human/ABCA7 GO:0033344 cholesterol efflux ARBA:ARBA00092042 KEEP_AS_NON_CORE leaf (0) 0 human/ABCA7 GO:0033700 phospholipid efflux ARBA:ARBA00084158 ACCEPT leaf (0) 0 human/ABCA7 GO:0034188 apolipoprotein A-I receptor activity ARBA:ARBA00090478 ACCEPT leaf (0) 0 human/ABCA7 GO:0034205 amyloid-beta formation ARBA:ARBA00090578 MODIFY leaf (0) 0 NEEDS_MORE_SPECIFIC true but uninformative replacement term Use directional regulation terms to avoid implying ABCA7 is a positive component of amyloid-beta formation. human/ABCA7 GO:0140328 floppase activity ARBA:ARBA00086582 ACCEPT specific (1-20) 8 human/ABCA7 GO:1902991 regulation of amyloid precursor protein catabolic process ARBA:ARBA00090680 ACCEPT specific (1-20) 5 human/ABCB10 GO:0031966 mitochondrial membrane ARBA:ARBA00026364 KEEP_AS_NON_CORE general (21-200) 36 human/ABCB10 GO:0042802 identical protein binding ARBA:ARBA00027930 KEEP_AS_NON_CORE specific (1-20) 1 human/ABCB4 GO:0045332 phospholipid translocation ARBA:ARBA00026752 ACCEPT specific (1-20) 12 human/ABCB4 GO:0090554 phosphatidylcholine floppase activity ARBA:ARBA00088274 ACCEPT leaf (0) 0 human/ABCB7 GO:0006879 intracellular iron ion homeostasis ARBA:ARBA00035735 ACCEPT general (21-200) 29 human/ABCB7 GO:0015232 heme transmembrane transporter activity ARBA:ARBA00027969 REMOVE specific (1-20) 2 WRONG_ACTIVITY wrong manual WRONG_ACTIVITY ABCB7 is an Fe-S cluster transporter, not a heme transporter. The transported substrate has been biochemically characterized as [2Fe-2S](GS)4 (glutathione- coordinated iron-sulfur cluster) (PMID:33157103). ABCB7 affects heme biosynthesis indirectly through the FECH-ABCB7-ABCB10 complex and by providing Fe-S clusters for iron regulation, but it does not transport heme itself. human/ABCB7 GO:0034755 iron ion transmembrane transport ARBA:ARBA00043448 MODIFY specific (1-20) 18 NEEDS_MORE_SPECIFIC true but uninformative replacement term ABCB7 does not transport free iron ions. It exports [2Fe-2S](GS)4, a glutathione-coordinated iron-sulfur cluster complex. The term GO:0140466 (iron-sulfur cluster export from the mitochondrion) is more accurate. human/ABCC6 GO:0009410 response to xenobiotic stimulus ARBA:ARBA00092608 KEEP_AS_NON_CORE general (21-200) 74 human/ABCC6 GO:0046942 carboxylic acid transport ARBA:ARBA00027271 ACCEPT very general (>200 descendants) 467 human/ABCC8 GO:0050796 regulation of insulin secretion ARBA:ARBA00091593 ACCEPT specific (1-20) 5 human/ABCC9 GO:0022857 transmembrane transporter activity ARBA:ARBA00028127 MODIFY very general (>200 descendants) 990 NEEDS_MORE_SPECIFIC true but uninformative replacement term ARBA00028127 predicts transmembrane transporter activity from the ABC-family context. SUR2 binds and regulates Kir6 channels; Kir6 provides the ion-permeation pathway. Replace the independently enabled transporter function with potassium channel regulator activity, while retaining the separate contributes_to channel annotations and transport-process participation. human/ABCC9 GO:0033198 response to ATP ARBA:ARBA00092810 ACCEPT specific (1-20) 2 human/ABCC9 GO:0071805 potassium ion transmembrane transport ARBA:ARBA00028321 ACCEPT general (21-200) 44 human/ABCD1 GO:0019217 regulation of fatty acid metabolic process ARBA:ARBA00084953 KEEP_AS_NON_CORE general (21-200) 29 human/ABCD1 GO:0045834 positive regulation of lipid metabolic process ARBA:ARBA00086378 KEEP_AS_NON_CORE general (21-200) 65 human/ABCE1 GO:0006412 translation ARBA:ARBA00027100 MARK_AS_OVER_ANNOTATED general (21-200) 159 TOO_GENERAL true but uninformative more precise The annotation is not wrong, but ribosome disassembly, translational termination, and rescue of stalled cytosolic ribosome are more precise and already present. human/ABCG5 GO:0046983 protein dimerization activity ARBA:ARBA00027598 MODIFY specific (1-20) 2 NEEDS_MORE_SPECIFIC true but uninformative replacement term ARBA00027598 propagates generic protein dimerization; its rule internals were not inspected. Direct human G5/G8 purification and structure support the more informative heterodimerization term. This precision correction does not assert that all observed self-association or higher-order assembly is impossible (PMID:16893193; PMID:27144356). human/ABCG8 GO:0006869 lipid transport ARBA:ARBA00027046 MODIFY general (21-200) 174 NEEDS_MORE_SPECIFIC true but uninformative replacement term The ARBA lipid-transport assignment is compatible with ABCG8 but does not capture its established neutral-sterol cargo. Refine to sterol transport using human G5G8 biliary export and the curated cholesterol/sitosterol reaction, rather than assuming that the rule itself establishes substrate specificity. human/ABCG8 GO:0046983 protein dimerization activity ARBA:ARBA00027598 MODIFY specific (1-20) 2 NEEDS_MORE_SPECIFIC true but uninformative replacement term The broad ARBA dimerization term can be refined to the well-established human G5/G8 heterodimerization activity. This refinement does not assert that homodimers or other associations can never occur under overexpression conditions; it identifies the partner-dependent physiological export assembly. human/ABHD12 GO:0006660 phosphatidylserine catabolic process ARBA:ARBA00087338 ACCEPT leaf (0) 0 human/ABI2 GO:0017124 SH3 domain binding ARBA:ARBA00085857 ACCEPT leaf (0) 0 human/ABI2 GO:0031209 SCAR complex ARBA:ARBA00086418 ACCEPT leaf (0) 0 human/ABI2 GO:0032433 filopodium tip ARBA:ARBA00084321 ACCEPT leaf (0) 0 human/ABI2 GO:0035591 signaling adaptor activity ARBA:ARBA00090724 ACCEPT specific (1-20) 5 human/ABL1 GO:0001784 phosphotyrosine residue binding ARBA:ARBA00089668 ACCEPT leaf (0) 0 human/ABL1 GO:0002252 immune effector process ARBA:ARBA00033862 MARK_AS_OVER_ANNOTATED general (21-200) 135 TOO_GENERAL true but uninformative broad While ABL1 does function in T cell migration and differentiation, this extremely broad term provides little functional insight. human/ABL1 GO:0002429 immune response-activating cell surface receptor signaling pathway ARBA:ARBA00089168 MARK_AS_OVER_ANNOTATED general (21-200) 36 INDIRECT_EFFECT overreach downstream ABL1 functions downstream of BCR and other immune receptors but this is not a specific evolved function. The annotation is too broad. human/ABL1 GO:0003785 actin monomer binding ARBA:ARBA00028459 ACCEPT leaf (0) 0 human/ABL1 GO:0005829 cytosol ARBA:ARBA00029243 ACCEPT general (21-200) 73 human/ABL1 GO:0006909 phagocytosis ARBA:ARBA00027650 KEEP_AS_NON_CORE specific (1-20) 15 human/ABL1 GO:0007204 positive regulation of cytosolic calcium ion concentration ARBA:ARBA00028136 KEEP_AS_NON_CORE specific (1-20) 8 human/ABL1 GO:0010468 regulation of gene expression ARBA:ARBA00028334 KEEP_AS_NON_CORE very general (>200 descendants) 874 human/ABL1 GO:0010506 regulation of autophagy ARBA:ARBA00043536 MARK_AS_OVER_ANNOTATED general (21-200) 35 UNCLASSIFIED unclassified Similar to GO:0006914, this is over-annotation. ABL1's primary role is in lysosomal trafficking and acidification, not autophagy regulation per se. human/ABL1 GO:0010557 positive regulation of macromolecule biosynthetic process ARBA:ARBA00027412 MARK_AS_OVER_ANNOTATED very general (>200 descendants) 270 TOO_GENERAL true but uninformative general This term is too general to provide meaningful functional information about ABL1. No specific evidence supports this as a core function. human/ABL1 GO:0010595 positive regulation of endothelial cell migration ARBA:ARBA00092351 KEEP_AS_NON_CORE specific (1-20) 5 human/ABL1 GO:0030100 regulation of endocytosis ARBA:ARBA00085851 KEEP_AS_NON_CORE general (21-200) 48 human/ABL1 GO:0032956 regulation of actin cytoskeleton organization ARBA:ARBA00028808 ACCEPT general (21-200) 58 human/ABL1 GO:0045595 regulation of cell differentiation ARBA:ARBA00028479 KEEP_AS_NON_CORE very general (>200 descendants) 697 human/ABL1 GO:0045785 positive regulation of cell adhesion ARBA:ARBA00026687 KEEP_AS_NON_CORE general (21-200) 74 human/ABL1 GO:0048008 platelet-derived growth factor receptor signaling pathway ARBA:ARBA00090281 KEEP_AS_NON_CORE specific (1-20) 12 human/ABL1 GO:0051726 regulation of cell cycle ARBA:ARBA00029144 KEEP_AS_NON_CORE very general (>200 descendants) 377 human/ABL1 GO:1901701 cellular response to oxygen-containing compound ARBA:ARBA00027483 KEEP_AS_NON_CORE very general (>200 descendants) 308 human/ABL1 GO:1902531 regulation of intracellular signal transduction ARBA:ARBA00027126 ACCEPT very general (>200 descendants) 278 human/ABR GO:0007264 small GTPase-mediated signal transduction ARBA:ARBA00044393 MODIFY specific (1-20) 10 NEEDS_MORE_SPECIFIC true but uninformative replacement term GO:0007264's definition is 'An intracellular signaling cassette in which a small monomeric GTPase relays a signal'. ABR is not the relaying GTPase; it is the GAP and GEF that switches one off and on. The regulation-branch counterpart GO:0051056 states exactly this and is already in GOA from Reactome. Supported only by an ARBA machine-learning rule (ARBA:ARBA00044393) with no gene-specific evidence, so there is no experimental call being overruled here. human/ACACA GO:0006637 acyl-CoA metabolic process ARBA:ARBA00028700 MARK_AS_OVER_ANNOTATED general (21-200) 51 TOO_GENERAL true but uninformative broad ARBA electronic annotation to the broad term acyl-CoA metabolic process. While malonyl-CoA is technically an acyl-CoA, this general term is less informative than the specific and already-annotated malonyl-CoA biosynthetic process (GO:2001295) and fatty acid biosynthetic process (GO:0006633). Over-annotation via a generic term. human/ACACB GO:0006637 acyl-CoA metabolic process ARBA:ARBA00028700 KEEP_AS_NON_CORE general (21-200) 51 human/ACAD9 GO:0006631 fatty acid metabolic process ARBA:ARBA00028669 MODIFY general (21-200) 94 NEEDS_MORE_SPECIFIC true but uninformative replacement term Refine the existing process assertion to GO:0006635. ACAD9 itself catalyzes the acyl-CoA dehydrogenation step, and human HEK293 knockout/rescue experiments support its context-dependent contribution to fatty acid oxidation (PMID:16020546; PMID:25721401). This supplies the precise process used in the enzymatic core without adding a redundant NEW annotation. The original ARBA rule predicates remain uninspected; the refinement relies on primary human evidence. human/ACAD9 GO:0031966 mitochondrial membrane ARBA:ARBA00026364 ACCEPT general (21-200) 36 human/ACADS GO:0005739 mitochondrion ARBA:ARBA00026962 ACCEPT general (21-200) 70 human/ACADS GO:0033539 fatty acid beta-oxidation using acyl-CoA dehydrogenase ARBA:ARBA00085069 ACCEPT leaf (0) 0 human/ACADSB GO:0005739 mitochondrion ARBA:ARBA00026962 ACCEPT general (21-200) 70 human/ACADSB GO:0006631 fatty acid metabolic process ARBA:ARBA00028669 KEEP_AS_NON_CORE general (21-200) 94 human/ACADSB GO:0046395 carboxylic acid catabolic process ARBA:ARBA00027882 ACCEPT general (21-200) 174 human/ACADVL GO:0006635 fatty acid beta-oxidation ARBA:ARBA00028692 ACCEPT specific (1-20) 2 human/ACADVL GO:0031966 mitochondrial membrane ARBA:ARBA00026364 ACCEPT general (21-200) 36 human/ACAN GO:0005796 Golgi lumen ARBA:ARBA00028705 KEEP_AS_NON_CORE specific (1-20) 2 human/ACAN GO:0043202 lysosomal lumen ARBA:ARBA00029034 KEEP_AS_NON_CORE specific (1-20) 3 human/ACAN GO:0140150 gel phase of interstitial matrix ARBA:ARBA00096892 ACCEPT leaf (0) 0 human/ACIN1 GO:0031981 nuclear lumen ARBA:ARBA00026536 KEEP_AS_NON_CORE general (21-200) 139 human/ACLY GO:0006637 acyl-CoA metabolic process ARBA:ARBA00028700 KEEP_AS_NON_CORE general (21-200) 51 human/ACOX1 GO:0005782 peroxisomal matrix ARBA:ARBA00088448 ACCEPT specific (1-20) 2 human/ACOX1 GO:0016491 oxidoreductase activity ARBA:ARBA00028747 MODIFY very general (>200 descendants) 1810 NEEDS_MORE_SPECIFIC true but uninformative replacement term The broad ARBA assignment is chemically correct. Human enzyme studies establish the donor substrate class and direct oxygen reduction, permitting a specific oxidase term without inventing a new function. human/ACOX2 GO:0005782 peroxisomal matrix ARBA:ARBA00088448 ACCEPT specific (1-20) 2 human/ACOX2 GO:0016491 oxidoreductase activity ARBA:ARBA00028747 MODIFY very general (>200 descendants) 1810 NEEDS_MORE_SPECIFIC true but uninformative replacement term Human substrate assays and the UniProt catalytic reaction specify acyl-CoA oxidation with oxygen reduction and hydrogen-peroxide formation. They support the specific molecular function. The ARBA rule predicates were not inspected independently; the refinement follows the independent chemistry. human/ACOX2 GO:0033540 fatty acid beta-oxidation using acyl-CoA oxidase ARBA:ARBA00085031 ACCEPT leaf (0) 0 human/ACOX3 GO:0005782 peroxisomal matrix ARBA:ARBA00088448 ACCEPT specific (1-20) 2 human/ACTR1A GO:0005815 microtubule organizing center ARBA:ARBA00029135 KEEP_AS_NON_CORE general (21-200) 42 human/ACTR1B GO:0005815 microtubule organizing center ARBA:ARBA00029135 KEEP_AS_NON_CORE general (21-200) 42 human/ACTR5 GO:0006259 DNA metabolic process ARBA:ARBA00028839 MARK_AS_OVER_ANNOTATED very general (>200 descendants) 285 TOO_GENERAL true but uninformative adds no ACTR5 already carries GO:0006302 double-strand break repair, GO:0070914 UV-damage excision repair, GO:0006275 regulation of DNA replication and GO:0060382 regulation of DNA strand elongation, all of which are descendants of GO:0006259. The row therefore adds no information and is not independent evidence -- ARBA rules are pattern-matched over existing annotation, so the parent is recovering what the children already assert. human/ACTR5 GO:0033044 regulation of chromosome organization ARBA:ARBA00029256 MARK_AS_OVER_ANNOTATED general (21-200) 140 TOO_GENERAL true but uninformative restates ACTR5 holds GO:0033044 already, by IMP from PMID:26340092 via ComplexPortal. This ARBA row restates it from a machine-learning rule with no gene-product source, so it neither corroborates nor extends the claim. The substantive assessment of the term is on the IMP row, where the underlying experiment is INO80-complex knockdown. human/ACTR5 GO:0051052 regulation of DNA metabolic process ARBA:ARBA00027282 MARK_AS_OVER_ANNOTATED general (21-200) 185 TOO_GENERAL true but uninformative already annotated GO:0006275 and GO:0060382, both already annotated to ACTR5, are descendants of GO:0051052. Same ARBA-rule provenance and same redundancy argument as the GO:0006259 row. human/ACTR8 GO:0033044 regulation of chromosome organization ARBA:ARBA00029256 KEEP_AS_NON_CORE general (21-200) 140 human/ACTR8 GO:0051052 regulation of DNA metabolic process ARBA:ARBA00027282 KEEP_AS_NON_CORE general (21-200) 185 human/ADA GO:0006154 adenosine catabolic process ARBA:ARBA00084293 ACCEPT leaf (0) 0 human/ADGRA2 GO:0060070 canonical Wnt signaling pathway ARBA:ARBA00026624 ACCEPT specific (1-20) 5 human/ADGRA2 GO:1990909 Wnt signalosome ARBA:ARBA00089285 ACCEPT leaf (0) 0 human/ADGRV1 GO:0005737 cytoplasm ARBA:ARBA00026971 KEEP_AS_NON_CORE very general (>200 descendants) 1146 human/ADGRV1 GO:0007605 sensory perception of sound ARBA:ARBA00033578 ACCEPT specific (1-20) 2 human/ADGRV1 GO:0032991 protein-containing complex ARBA:ARBA00028902 MODIFY very general (>200 descendants) 2083 NEEDS_MORE_SPECIFIC true but uninformative replacement term GO:0032991 is the root of the complex branch and conveys no specific information. The USH2 quaternary complex (ADGRV1-USH2A-WHRN-PDZD7) is experimentally established [PMID:25406310]; replace with the specific term. human/ADGRV1 GO:0048513 animal organ development ARBA:ARBA00029247 MODIFY very general (>200 descendants) 1888 NEEDS_MORE_SPECIFIC true but uninformative replacement term ADGRV1 supplies the ankle-link structure in developing cochlear hair bundles. Full PMID:17567809 localizes the receptor to these links and documents disorganized bundles after its loss. GO:0060122 inner ear receptor cell stereocilium organization captures this specific structural contribution more precisely than animal organ development. The broader inner ear development assertion is independently retained as non-core context; the ARBA rule internals remain unresolved. human/ADGRV1 GO:0050793 regulation of developmental process ARBA:ARBA00028689 KEEP_AS_NON_CORE very general (>200 descendants) 1542 human/ADGRV1 GO:0050953 sensory perception of light stimulus ARBA:ARBA00091469 KEEP_AS_NON_CORE specific (1-20) 4 human/ADPRS GO:0071451 cellular response to superoxide ARBA:ARBA00043602 MODIFY specific (1-20) 2 OTHER_TERM different term needed replacement term The term names the wrong reactive oxygen species. Every experiment behind this term used HYDROGEN PEROXIDE, not superoxide. GO:0070301 cellular response to hydrogen peroxide and GO:0071451 cellular response to superoxide are SIBLINGS under GO:0034614 cellular response to reactive oxygen species - verified by fetching both ancestor closures, neither contains the other - so this is not a too-general parent that quietly covers the data, it is a different chemical species. The defect originates upstream at the mouse MGI IMP (PMID:24191052) and has propagated to all 33 gene products under PANTHER:PTN008564042. ARBA:ARBA00043602 is a machine-learned rule trained on the existing annotation set, so it inherits rather than corroborates the error. It should follow the IMP and IBA rows to GO:0070301. human/ADRB2 GO:0004939 beta-adrenergic receptor activity ARBA:ARBA00089398 MODIFY specific (1-20) 3 NEEDS_MORE_SPECIFIC true but uninformative replacement term ADRB2 should be annotated to beta2-adrenergic receptor activity rather than the broader beta-adrenergic receptor parent. human/AGFG1 GO:0005737 cytoplasm ARBA:ARBA00026971 KEEP_AS_NON_CORE very general (>200 descendants) 1146 human/AGO1 GO:0003725 double-stranded RNA binding ARBA:ARBA00028403 ACCEPT specific (1-20) 2 human/AGO1 GO:0003727 single-stranded RNA binding ARBA:ARBA00089173 ACCEPT specific (1-20) 10 human/AGO1 GO:0031054 pre-miRNA processing ARBA:ARBA00027506 ACCEPT specific (1-20) 2 human/AGO1 GO:0035278 miRNA-mediated gene silencing by inhibition of translation ARBA:ARBA00091152 ACCEPT leaf (0) 0 human/AGO1 GO:0036464 cytoplasmic ribonucleoprotein granule ARBA:ARBA00026950 ACCEPT specific (1-20) 14 human/AGO1 GO:0070578 RISC-loading complex ARBA:ARBA00085164 UNDECIDED leaf (0) 0 human/AGO1 GO:0070922 RISC complex assembly ARBA:ARBA00086266 ACCEPT leaf (0) 0 human/AGO2 GO:0003725 double-stranded RNA binding ARBA:ARBA00028403 ACCEPT specific (1-20) 2 human/AGO2 GO:0003727 single-stranded RNA binding ARBA:ARBA00089173 ACCEPT specific (1-20) 10 human/AGO2 GO:0036464 cytoplasmic ribonucleoprotein granule ARBA:ARBA00026950 ACCEPT specific (1-20) 14 human/AGO2 GO:0070922 RISC complex assembly ARBA:ARBA00086266 ACCEPT leaf (0) 0 human/AGO3 GO:0003725 double-stranded RNA binding ARBA:ARBA00028403 MARK_AS_OVER_ANNOTATED specific (1-20) 2 TOO_GENERAL true but uninformative broad The informative molecular function is Argonaute small-RNA/miRNA binding within RISC rather than a broad nucleic-acid or RNA-binding label. human/AGO3 GO:0003727 single-stranded RNA binding ARBA:ARBA00089173 MARK_AS_OVER_ANNOTATED specific (1-20) 10 TOO_GENERAL true but uninformative broad The informative molecular function is Argonaute small-RNA/miRNA binding within RISC rather than a broad nucleic-acid or RNA-binding label. human/AGO3 GO:0031054 pre-miRNA processing ARBA:ARBA00027506 MARK_AS_OVER_ANNOTATED specific (1-20) 2 UNCLASSIFIED unclassified The better-supported role is as a loaded Argonaute effector after small-RNA processing, not as the Drosha/Dicer processing enzyme for pre-miRNAs. human/AGO3 GO:0036464 cytoplasmic ribonucleoprotein granule ARBA:ARBA00026950 ACCEPT specific (1-20) 14 human/AGO3 GO:0070578 RISC-loading complex ARBA:ARBA00085164 ACCEPT leaf (0) 0 human/AGO3 GO:0070922 RISC complex assembly ARBA:ARBA00086266 ACCEPT leaf (0) 0 human/AGO4 GO:0003725 double-stranded RNA binding ARBA:ARBA00028403 ACCEPT specific (1-20) 2 human/AGO4 GO:0003727 single-stranded RNA binding ARBA:ARBA00089173 ACCEPT specific (1-20) 10 human/AGO4 GO:0031054 pre-miRNA processing ARBA:ARBA00027506 ACCEPT specific (1-20) 2 human/AGO4 GO:0036464 cytoplasmic ribonucleoprotein granule ARBA:ARBA00026950 ACCEPT specific (1-20) 14 human/AGO4 GO:0070578 RISC-loading complex ARBA:ARBA00085164 ACCEPT leaf (0) 0 human/AGO4 GO:0070922 RISC complex assembly ARBA:ARBA00086266 ACCEPT leaf (0) 0 human/AGR2 GO:0002162 dystroglycan binding ARBA:ARBA00087703 KEEP_AS_NON_CORE leaf (0) 0 human/AGR3 GO:0002162 dystroglycan binding ARBA:ARBA00087703 KEEP_AS_NON_CORE leaf (0) 0 human/AGRN GO:0005576 extracellular region ARBA:ARBA00027128 ACCEPT very general (>200 descendants) 276 human/AGRN GO:0007010 cytoskeleton organization ARBA:ARBA00026736 KEEP_AS_NON_CORE very general (>200 descendants) 224 human/AGRN GO:0007399 nervous system development ARBA:ARBA00027428 ACCEPT very general (>200 descendants) 913 human/AGRN GO:0050808 synapse organization ARBA:ARBA00029184 ACCEPT general (21-200) 75 human/AGRN GO:0061024 membrane organization ARBA:ARBA00028824 ACCEPT very general (>200 descendants) 283 human/AGRN GO:0099536 synaptic signaling ARBA:ARBA00026596 ACCEPT general (21-200) 110 human/AGXT GO:0005737 cytoplasm ARBA:ARBA00026971 ACCEPT very general (>200 descendants) 1146 human/AGXT GO:0047635 L-alanine:oxo-acid transaminase activity ARBA:ARBA00092993 MODIFY specific (1-20) 7 NEEDS_MORE_SPECIFIC true but uninformative replacement term The current GO:0047635 definition describes L-alanine transfer to a generic 2-oxocarboxylate, yielding an L-alpha-amino acid. Human AGXT has a specifically measured glyoxylate-to-glycine reaction. GO:0008453 conveys that chemistry without assuming the two terms are a formal parent-child pair or that every oxo-acid acceptor is used. The reverse serine reaction is covered independently by GO:0004760. ARBA00092993 predicates remain uninspected. human/AGXT2 GO:0005759 mitochondrial matrix ARBA:ARBA00028628 ACCEPT specific (1-20) 17 human/AGXT2 GO:0140385 amino acid transaminase activity ARBA:ARBA00096929 ACCEPT general (21-200) 46 human/AHNAK GO:0005737 cytoplasm ARBA:ARBA00026971 KEEP_AS_NON_CORE very general (>200 descendants) 1146 human/AHNAK GO:0005886 plasma membrane ARBA:ARBA00027801 ACCEPT very general (>200 descendants) 415 human/AHNAK2 GO:0005737 cytoplasm ARBA:ARBA00026971 KEEP_AS_NON_CORE very general (>200 descendants) 1146 human/AHNAK2 GO:0005886 plasma membrane ARBA:ARBA00027801 ACCEPT very general (>200 descendants) 415 human/AHR GO:0004879 nuclear receptor activity ARBA:ARBA00035557 ACCEPT specific (1-20) 5 human/AHR GO:0045893 positive regulation of DNA-templated transcription ARBA:ARBA00029082 ACCEPT general (21-200) 42 human/AHR GO:0051239 regulation of multicellular organismal process ARBA:ARBA00028859 MARK_AS_OVER_ANNOTATED very general (>200 descendants) 1807 INDIRECT_EFFECT overreach phenotype AHR affects development, cell cycle, apoptosis, and organism-level phenotypes through transcriptional programs, but these high-level process annotations risk implying a direct pathway role that is not supported by the specific evidence used here. human/AHR GO:1904613 cellular response to 2,3,7,8-tetrachlorodibenzodioxine ARBA:ARBA00035547 ACCEPT leaf (0) 0 human/AHR GO:1990837 sequence-specific double-stranded DNA binding ARBA:ARBA00028376 ACCEPT general (21-200) 48 human/AICDA GO:0005737 cytoplasm ARBA:ARBA00026971 ACCEPT very general (>200 descendants) 1146 human/AICDA GO:0016445 somatic diversification of immunoglobulins ARBA:ARBA00088467 ACCEPT specific (1-20) 19 human/AIFM1 GO:0043068 positive regulation of programmed cell death ARBA:ARBA00027743 ACCEPT general (21-200) 87 human/AIP GO:0051082 unfolded protein binding ARBA:ARBA00027557 MODIFY leaf (0) 0 OTHER_TERM different term needed replacement term GO:0051082 is now formally obsolete, and the project-level decision for AIP is to reclassify this annotation to GO:0051879 (Hsp90 protein binding). This captures AIP's specific, well-supported co-chaperone/scaffold activity without overgeneralizing AIP as a protein folding chaperone. human/AIRE GO:0002507 tolerance induction ARBA:ARBA00088939 MODIFY general (21-200) 36 NEEDS_MORE_SPECIFIC true but uninformative replacement term The broad ARBA tolerance term is biologically sound. Human genetics and transcriptional assays justify refinement to central tolerance induction to self antigen. Do not also propose peripheral tolerance as a replacement while its source-specific participation remains unresolved. The ARBA rule predicates themselves were not inspected. human/AIRE GO:0006955 immune response ARBA:ARBA00026313 ACCEPT very general (>200 descendants) 207 human/AIRE GO:0045944 positive regulation of transcription by RNA polymerase II ARBA:ARBA00027996 ACCEPT specific (1-20) 12 human/AK2 GO:0055086 nucleobase-containing small molecule metabolic process ARBA:ARBA00027681 MODIFY very general (>200 descendants) 576 NEEDS_MORE_SPECIFIC true but uninformative replacement term The direct AK2 step is reversible adenylate interconversion, already represented by the curated pathway row. GO:0015949 captures that work more specifically than generic nucleobase-containing small-molecule metabolism. This is a source-specific refinement, not an additional NEW process. ARBA conditions were not recovered; the target judgment rests on measured chemistry. human/AK4P3 GO:0055086 nucleobase-containing small molecule metabolic process ARBA:ARBA00027681 ACCEPT very general (>200 descendants) 576 human/AKAP7 GO:0051018 protein kinase A binding ARBA:ARBA00088054 MODIFY specific (1-20) 2 NEEDS_MORE_SPECIFIC true but uninformative replacement term "AKAP7 binds the PKA regulatory subunit specifically, and the structural evidence is on this entry's own isoform [PMID:27102985 ""Here, we elucidated the structure of an extended PKA-binding domain of AKAP18β bound to the D/D domain of the regulatory RIIα subunits of PKA.""]; all isoforms share the site [PMID:10613906 ""The AKAP18 isoforms share a common R subunit binding site, but have distinct targeting domains.""]. GO:0034237 protein kinase A regulatory subunit binding is the direct, childless child of GO:0051018 that says exactly this. The comparator check is unusually clean: AKAP1, AKAP5 and AKAP9 all carry GO:0034237, including by IBA, and so does the mouse AKAP7 ortholog by IDA. Human AKAP7 is the outlier carrying only the parent, so this harmonises it rather than inventing anything." human/AKR1C4 GO:0008106 alcohol dehydrogenase (NADP+) activity ARBA:ARBA00092671 ACCEPT specific (1-20) 9 human/AKR1C4 GO:0008202 steroid metabolic process ARBA:ARBA00027309 ACCEPT general (21-200) 73 human/AKR1C4 GO:0032787 monocarboxylic acid metabolic process ARBA:ARBA00027288 ACCEPT very general (>200 descendants) 286 human/AKR1C4 GO:0042445 hormone metabolic process ARBA:ARBA00028011 ACCEPT general (21-200) 85 human/AKR1C8 GO:0008106 alcohol dehydrogenase (NADP+) activity ARBA:ARBA00092671 KEEP_AS_NON_CORE specific (1-20) 9 human/AKR1C8 GO:0008202 steroid metabolic process ARBA:ARBA00027309 MARK_AS_OVER_ANNOTATED general (21-200) 73 WRONG_PARALOG wrong paralog "AKR1C8 is an AKR1C-family aldo-keto reductase [file:genes/human/AKR1C8/AKR1C8-uniprot.txt ""Belongs to the aldo/keto reductase family.""] and keeps the full catalytic tetrad [file:genes/human/AKR1C8/AKR1C8-bioinformatics/RESULTS.md ""All four catalytic tetrad residues are conserved in AKR1C8 at D53, Y58, K87 and H120.""], aligning at 68% identity to AKR1C1 [file:genes/human/AKR1C8/AKR1C8-bioinformatics/RESULTS.md ""| AKR1C8 | Q5T2L2 | 326 | 68% | D53 | Y58 | K87 | H120 |""]. The tetrad does not speak to substrate [file:genes/human/AKR1C8/AKR1C8-bioinformatics/RESULTS.md ""A conserved tetrad is consistent with NADP(H)-dependent carbonyl reductase activity but does not establish it, and it says nothing about substrate specificity, which differs among AKR1C enzymes.""]. Close AKR1C paralogs differ sharply in which steroids and prostaglandins they reduce, and no substrate has been tested for human AKR1C8, so this rule-derived substrate or pathway claim is not supported beyond family membership." human/AKR1C8 GO:0032787 monocarboxylic acid metabolic process ARBA:ARBA00027288 MARK_AS_OVER_ANNOTATED very general (>200 descendants) 286 WRONG_PARALOG wrong paralog "AKR1C8 is an AKR1C-family aldo-keto reductase [file:genes/human/AKR1C8/AKR1C8-uniprot.txt ""Belongs to the aldo/keto reductase family.""] and keeps the full catalytic tetrad [file:genes/human/AKR1C8/AKR1C8-bioinformatics/RESULTS.md ""All four catalytic tetrad residues are conserved in AKR1C8 at D53, Y58, K87 and H120.""], aligning at 68% identity to AKR1C1 [file:genes/human/AKR1C8/AKR1C8-bioinformatics/RESULTS.md ""| AKR1C8 | Q5T2L2 | 326 | 68% | D53 | Y58 | K87 | H120 |""]. The tetrad does not speak to substrate [file:genes/human/AKR1C8/AKR1C8-bioinformatics/RESULTS.md ""A conserved tetrad is consistent with NADP(H)-dependent carbonyl reductase activity but does not establish it, and it says nothing about substrate specificity, which differs among AKR1C enzymes.""]. Close AKR1C paralogs differ sharply in which steroids and prostaglandins they reduce, and no substrate has been tested for human AKR1C8, so this rule-derived substrate or pathway claim is not supported beyond family membership." human/AKR1C8 GO:0042445 hormone metabolic process ARBA:ARBA00028011 MARK_AS_OVER_ANNOTATED general (21-200) 85 WRONG_PARALOG wrong paralog "AKR1C8 is an AKR1C-family aldo-keto reductase [file:genes/human/AKR1C8/AKR1C8-uniprot.txt ""Belongs to the aldo/keto reductase family.""] and keeps the full catalytic tetrad [file:genes/human/AKR1C8/AKR1C8-bioinformatics/RESULTS.md ""All four catalytic tetrad residues are conserved in AKR1C8 at D53, Y58, K87 and H120.""], aligning at 68% identity to AKR1C1 [file:genes/human/AKR1C8/AKR1C8-bioinformatics/RESULTS.md ""| AKR1C8 | Q5T2L2 | 326 | 68% | D53 | Y58 | K87 | H120 |""]. The tetrad does not speak to substrate [file:genes/human/AKR1C8/AKR1C8-bioinformatics/RESULTS.md ""A conserved tetrad is consistent with NADP(H)-dependent carbonyl reductase activity but does not establish it, and it says nothing about substrate specificity, which differs among AKR1C enzymes.""]. Close AKR1C paralogs differ sharply in which steroids and prostaglandins they reduce, and no substrate has been tested for human AKR1C8, so this rule-derived substrate or pathway claim is not supported beyond family membership." human/AKR1C8 GO:0047023 androsterone dehydrogenase [NAD(P)+] activity ARBA:ARBA00098279 MODIFY leaf (0) 0 TOO_SPECIFIC overreach replacement term "AKR1C8 is an AKR1C-family aldo-keto reductase [file:genes/human/AKR1C8/AKR1C8-uniprot.txt ""Belongs to the aldo/keto reductase family.""] and keeps the full catalytic tetrad [file:genes/human/AKR1C8/AKR1C8-bioinformatics/RESULTS.md ""All four catalytic tetrad residues are conserved in AKR1C8 at D53, Y58, K87 and H120.""], aligning at 68% identity to AKR1C1 [file:genes/human/AKR1C8/AKR1C8-bioinformatics/RESULTS.md ""| AKR1C8 | Q5T2L2 | 326 | 68% | D53 | Y58 | K87 | H120 |""]. The tetrad does not speak to substrate [file:genes/human/AKR1C8/AKR1C8-bioinformatics/RESULTS.md ""A conserved tetrad is consistent with NADP(H)-dependent carbonyl reductase activity but does not establish it, and it says nothing about substrate specificity, which differs among AKR1C enzymes.""]. Close AKR1C paralogs differ sharply in which steroids and prostaglandins they reduce, and no substrate has been tested for human AKR1C8, so this rule-derived substrate or pathway claim is not supported beyond family membership. The defensible statement is NAD(P)-dependent oxidoreduction of a CH-OH group, so the row is generalized to GO:0016616, which is an ancestor of both this term and GO:0008106 (checked via OLS) and makes no substrate claim." human/AKR1D1 GO:0008106 alcohol dehydrogenase (NADP+) activity ARBA:ARBA00092671 UNDECIDED specific (1-20) 9 human/AKR1D1 GO:0032787 monocarboxylic acid metabolic process ARBA:ARBA00027288 ACCEPT very general (>200 descendants) 286 human/AKR1D1 GO:0042445 hormone metabolic process ARBA:ARBA00028011 ACCEPT general (21-200) 85 human/AKT1 GO:0030335 positive regulation of cell migration ARBA:ARBA00028907 KEEP_AS_NON_CORE general (21-200) 68 human/ALDH18A1 GO:0008652 amino acid biosynthetic process ARBA:ARBA00027355 ACCEPT general (21-200) 52 human/ALDOA GO:0006000 fructose metabolic process ARBA:ARBA00043337 KEEP_AS_NON_CORE specific (1-20) 3 human/ALDOA GO:0030388 fructose 1,6-bisphosphate metabolic process ARBA:ARBA00087539 ACCEPT leaf (0) 0 human/ALDOA GO:0070061 fructose binding ARBA:ARBA00092505 ACCEPT leaf (0) 0 human/ALDOB GO:0030388 fructose 1,6-bisphosphate metabolic process ARBA:ARBA00087539 ACCEPT leaf (0) 0 human/ALDOB GO:0070061 fructose binding ARBA:ARBA00092505 REMOVE leaf (0) 0 WRONG_ACTIVITY wrong manual WRONG_ACTIVITY The live GO:0070061 definition binds the unphosphorylated ketohexose fructose. ALDOB biochemical evidence instead establishes fructose 1-phosphate and fructose 1,6-bisphosphate substrates, including the complete assays in PMID:10625657. Those distinct ligands do not justify free-fructose binding. Remove this unsupported electronic assignment without claiming that an untested free-fructose interaction is chemically impossible; the exact ARBA derivation remains unresolved. human/ALG13 GO:0003824 catalytic activity ARBA:ARBA00027533 MODIFY very general (>200 descendants) 6405 NEEDS_MORE_SPECIFIC true but uninformative replacement term Human ALG13 isoform 2 in complex with ALG14 catalyzes formation of GlcNAc2-PP-dolichol (PMID:36200043). Replace the generic catalytic parent with GO:0004577 to express the measured chemistry. This does not assign the activity to every splice isoform or infer OTU catalysis from the long isoform sequence. human/ALG13 GO:0005737 cytoplasm ARBA:ARBA00026971 ACCEPT very general (>200 descendants) 1146 human/ALG3 GO:0006487 protein N-linked glycosylation ARBA:ARBA00085866 ACCEPT specific (1-20) 11 human/ALK GO:0030298 receptor signaling protein tyrosine kinase activator activity ARBA:ARBA00034178 UNDECIDED leaf (0) 0 human/ALKBH3 GO:0035515 oxidative RNA demethylase activity ARBA:ARBA00090591 ACCEPT specific (1-20) 3 human/ALKBH6 GO:0016706 2-oxoglutarate-dependent dioxygenase activity ARBA:ARBA00027633 ACCEPT general (21-200) 65 human/ALKBH7 GO:0016706 2-oxoglutarate-dependent dioxygenase activity ARBA:ARBA00027633 ACCEPT general (21-200) 65 human/ALPK2 GO:0003007 heart morphogenesis ARBA:ARBA00086699 KEEP_AS_NON_CORE general (21-200) 98 human/ALPK2 GO:0055013 cardiac muscle cell development ARBA:ARBA00084678 KEEP_AS_NON_CORE specific (1-20) 11 human/ALS2 GO:0030425 dendrite ARBA:ARBA00028031 ACCEPT general (21-200) 37 human/ALX1 GO:1990837 sequence-specific double-stranded DNA binding ARBA:ARBA00028376 ACCEPT general (21-200) 48 human/ALX3 GO:1990837 sequence-specific double-stranded DNA binding ARBA:ARBA00028376 ACCEPT general (21-200) 48 human/ALX4 GO:0048513 animal organ development ARBA:ARBA00029247 ACCEPT very general (>200 descendants) 1888 human/ALX4 GO:1990837 sequence-specific double-stranded DNA binding ARBA:ARBA00028376 ACCEPT general (21-200) 48 human/AMBRA1 GO:0006914 autophagy ARBA:ARBA00027757 MODIFY general (21-200) 49 NEEDS_MORE_SPECIFIC true but uninformative replacement term Direct literature supports AMBRA1 in autophagosome assembly/nucleation and positive regulation of autophagy rather than a generic autophagy process annotation. human/AMH GO:0007548 sex differentiation ARBA:ARBA00028749 ACCEPT general (21-200) 68 human/AMIGO1 GO:0043005 neuron projection ARBA:ARBA00027418 ACCEPT general (21-200) 135 human/AMIGO1 GO:1904064 positive regulation of cation transmembrane transport ARBA:ARBA00087210 ACCEPT general (21-200) 30 human/AMPD1 GO:0006753 nucleoside phosphate metabolic process ARBA:ARBA00027937 KEEP_AS_NON_CORE very general (>200 descendants) 441 human/AMPD2 GO:0006188 IMP biosynthetic process ARBA:ARBA00084268 ACCEPT specific (1-20) 2 human/AMPD2 GO:0097009 energy homeostasis ARBA:ARBA00090302 KEEP_AS_NON_CORE specific (1-20) 4 human/AMPD2 GO:0106380 purine ribonucleotide salvage ARBA:ARBA00090487 KEEP_AS_NON_CORE specific (1-20) 4 human/AMPD3 GO:0006753 nucleoside phosphate metabolic process ARBA:ARBA00027937 ACCEPT very general (>200 descendants) 441 human/ANAPC11 GO:0004842 ubiquitin-protein transferase activity ARBA:ARBA00026878 ACCEPT specific (1-20) 18 human/ANAPC11 GO:0031461 cullin-RING ubiquitin ligase complex ARBA:ARBA00027480 ACCEPT general (21-200) 29 human/ANAPC11 GO:0043161 proteasome-mediated ubiquitin-dependent protein catabolic process ARBA:ARBA00026940 ACCEPT specific (1-20) 13 human/ANAPC2 GO:0010498 proteasomal protein catabolic process ARBA:ARBA00028386 ACCEPT general (21-200) 21 human/ANAPC2 GO:0031461 cullin-RING ubiquitin ligase complex ARBA:ARBA00027480 MODIFY general (21-200) 29 NEEDS_MORE_SPECIFIC true but uninformative replacement term The broad cullin-RING ubiquitin ligase complex annotation is mechanistically related but less precise for ANAPC2. The more accurate cellular-component term is anaphase-promoting complex. human/ANG GO:0004540 RNA nuclease activity ARBA:ARBA00027859 ACCEPT general (21-200) 41 human/ANK1 GO:0005200 structural constituent of cytoskeleton ARBA:ARBA00085437 ACCEPT specific (1-20) 3 human/ANK1 GO:0005737 cytoplasm ARBA:ARBA00026971 ACCEPT very general (>200 descendants) 1146 human/ANK1 GO:0014731 spectrin-associated cytoskeleton ARBA:ARBA00090405 ACCEPT specific (1-20) 1 human/ANK1 GO:0048193 Golgi vesicle transport ARBA:ARBA00028135 ACCEPT general (21-200) 43 human/ANK1 GO:0071944 cell periphery ARBA:ARBA00027443 ACCEPT very general (>200 descendants) 493 human/ANK1 GO:0072657 protein localization to membrane ARBA:ARBA00029167 ACCEPT general (21-200) 53 human/ANK1 GO:1990778 protein localization to cell periphery ARBA:ARBA00027771 ACCEPT general (21-200) 40 human/ANK2 GO:0005737 cytoplasm ARBA:ARBA00026971 ACCEPT very general (>200 descendants) 1146 human/ANK2 GO:0016323 basolateral plasma membrane ARBA:ARBA00086715 UNDECIDED leaf (0) 0 human/ANK2 GO:0072659 protein localization to plasma membrane ARBA:ARBA00029169 ACCEPT specific (1-20) 7 human/ANKFY1 GO:0005768 endosome ARBA:ARBA00028568 ACCEPT general (21-200) 68 human/ANKFY1 GO:0016020 membrane ARBA:ARBA00028763 KEEP_AS_NON_CORE very general (>200 descendants) 895 human/ANKHD1 GO:0005634 nucleus ARBA:ARBA00026330 ACCEPT very general (>200 descendants) 473 human/ANKRD11 GO:0048705 skeletal system morphogenesis ARBA:ARBA00043345 KEEP_AS_NON_CORE general (21-200) 39 human/ANKRD11 GO:0060323 head morphogenesis ARBA:ARBA00091413 KEEP_AS_NON_CORE specific (1-20) 1 human/ANKRD11 GO:0060324 face development ARBA:ARBA00091412 KEEP_AS_NON_CORE specific (1-20) 1 human/ANKRD13A GO:0002091 negative regulation of receptor internalization ARBA:ARBA00088001 MODIFY specific (1-20) 1 TOO_SPECIFIC overreach replacement term "The inhibition is an overexpression phenotype [PMID:22298428 ""Finally, overexpression of wild-type as well as truncated-mutant Ankrd 13 proteins strongly inhibited rapid endocytosis of ubiquitinated EGFR from the surface in EGF-treated cells.""]. Truncated mutants [PMID:22298428 ""which were expected to act as dominant-negative versions""] inhibit as wild type does, which the authors read as [PMID:22298428 ""ectopic overexpression of not only truncated but also wild-type Ankrd 13 inhibits the function of endogenous Ankrd 13""]. They therefore pose the sign as open [PMID:22298428 ""raising the question of whether Ankrd 13 proteins have a stimulatory or inhibitory role in the process""] and conclude [PMID:22298428 ""we propose that Ankrd 13A, 13B, and 13D positively regulate the internalization of ligand-activated EGFR""]. RNAi could not test it because the siRNAs [PMID:22298428 ""failed to deplete the three Ankrd 13 mRNAs/proteins simultaneously""]. Independently, [PMID:34694569 ""USP30-AS1 induced HLA-I internalization from the cell membrane by up-regulating ANKRD13A, which might induce the immune escape of AML cells.""] GO:0002090 regulation of receptor internalization keeps what is shown without asserting a direction." human/ANKRD13A GO:0048471 perinuclear region of cytoplasm ARBA:ARBA00091589 ACCEPT specific (1-20) 7 human/ANKRD13A GO:0140036 ubiquitin-modified protein reader activity ARBA:ARBA00084857 ACCEPT specific (1-20) 1 human/ANKRD13B GO:0002091 negative regulation of receptor internalization ARBA:ARBA00088001 MODIFY specific (1-20) 1 TOO_SPECIFIC overreach replacement term "The inhibition is an overexpression phenotype [PMID:22298428 ""Finally, overexpression of wild-type as well as truncated-mutant Ankrd 13 proteins strongly inhibited rapid endocytosis of ubiquitinated EGFR from the surface in EGF-treated cells.""]. Truncated mutants [PMID:22298428 ""which were expected to act as dominant-negative versions""] inhibit as strongly as wild type, which the authors read as [PMID:22298428 ""ectopic overexpression of not only truncated but also wild-type Ankrd 13 inhibits the function of endogenous Ankrd 13""]. They therefore pose the sign as open [PMID:22298428 ""raising the question of whether Ankrd 13 proteins have a stimulatory or inhibitory role in the process""] and conclude [PMID:22298428 ""we propose that Ankrd 13A, 13B, and 13D positively regulate the internalization of ligand-activated EGFR""]. RNAi could not test this because the siRNAs [PMID:22298428 ""failed to deplete the three Ankrd 13 mRNAs/proteins simultaneously""]. So the negative term asserts a direction the evidence does not establish; GO:0002090 regulation of receptor internalization keeps what is shown." human/ANKRD13B GO:0048471 perinuclear region of cytoplasm ARBA:ARBA00091589 ACCEPT specific (1-20) 7 human/ANKRD13B GO:0140036 ubiquitin-modified protein reader activity ARBA:ARBA00084857 ACCEPT specific (1-20) 1 human/ANKRD13D GO:0002091 negative regulation of receptor internalization ARBA:ARBA00088001 MODIFY specific (1-20) 1 TOO_SPECIFIC overreach replacement term "The inhibition is an overexpression phenotype [PMID:22298428 ""In striking contrast, EGFR was mostly retained at the surface in cells overexpressing FLAG-tagged Ankrd 13A, 13B, or 13D (Figure 7, C–E′′).""]. Truncated mutants [PMID:22298428 ""which were expected to act as dominant-negative versions""] inhibit as wild type does, which the authors read as [PMID:22298428 ""ectopic overexpression of not only truncated but also wild-type Ankrd 13 inhibits the function of endogenous Ankrd 13""]. They therefore pose the sign as open [PMID:22298428 ""raising the question of whether Ankrd 13 proteins have a stimulatory or inhibitory role in the process""] and conclude [PMID:22298428 ""we propose that Ankrd 13A, 13B, and 13D positively regulate the internalization of ligand-activated EGFR""]; UniProt follows this [file:human/ANKRD13D/ANKRD13D-uniprot.txt ""ubiquitin. Positively regulates the internalization of ligand-activated""]. RNAi could not test it because the siRNAs [PMID:22298428 ""failed to deplete the three Ankrd 13 mRNAs/proteins simultaneously""]. GO:0002090 regulation of receptor internalization keeps what is shown without asserting the direction. GO:0002092 positive regulation of receptor internalization, which the UniProt text would suggest, is not proposed: it is the authors' interpretation, and no loss-of-function experiment has tested it." human/ANKRD13D GO:0048471 perinuclear region of cytoplasm ARBA:ARBA00091589 UNDECIDED specific (1-20) 7 human/ANKRD13D GO:0140036 ubiquitin-modified protein reader activity ARBA:ARBA00084857 ACCEPT specific (1-20) 1 human/ANKS4B GO:0120025 plasma membrane bounded cell projection ARBA:ARBA00028036 ACCEPT very general (>200 descendants) 303 human/ANO10 GO:0005254 chloride channel activity ARBA:ARBA00026476 KEEP_AS_NON_CORE specific (1-20) 12 human/ANO5 GO:0005254 chloride channel activity ARBA:ARBA00026476 KEEP_AS_NON_CORE specific (1-20) 12 human/ANXA1 GO:0019834 phospholipase A2 inhibitor activity ARBA:ARBA00085474 MARK_AS_OVER_ANNOTATED leaf (0) 0 UNCLASSIFIED unclassified Electronic propagation of a historically defined activity whose mechanism is substrate sequestration; overstates a direct enzyme-inhibitor function. human/ANXA1 GO:0031340 positive regulation of vesicle fusion ARBA:ARBA00086235 KEEP_AS_NON_CORE specific (1-20) 7 human/ANXA1 GO:0048306 calcium-dependent protein binding ARBA:ARBA00043551 KEEP_AS_NON_CORE specific (1-20) 1 human/ANXA1 GO:0051051 negative regulation of transport ARBA:ARBA00088037 KEEP_AS_NON_CORE very general (>200 descendants) 307 human/ANXA1 GO:0070062 extracellular exosome ARBA:ARBA00092504 ACCEPT specific (1-20) 2 human/AP1B1 GO:0005765 lysosomal membrane ARBA:ARBA00028563 ACCEPT specific (1-20) 12 human/AP1B1 GO:0012505 endomembrane system ARBA:ARBA00028953 MARK_AS_OVER_ANNOTATED very general (>200 descendants) 357 TOO_GENERAL true but uninformative broad While technically accurate, this term is too broad. More specific CC terms like GO:0032588 (trans-Golgi network membrane) and GO:0030121 (AP-1 adaptor complex) already capture AP-1B1's localization with greater precision. human/AP1G1 GO:0005768 endosome ARBA:ARBA00028568 ACCEPT general (21-200) 68 human/AP1G1 GO:0030659 cytoplasmic vesicle membrane ARBA:ARBA00026540 ACCEPT general (21-200) 107 human/AP1S1 GO:0032588 trans-Golgi network membrane ARBA:ARBA00033972 ACCEPT specific (1-20) 2 human/AP1S2 GO:0005737 cytoplasm ARBA:ARBA00026971 MODIFY very general (>200 descendants) 1146 NEEDS_MORE_SPECIFIC true but uninformative replacement term AP1S2 is cytoplasmic - it has no signal peptide or transmembrane segment and UniProt describes it as a peripheral membrane protein on the cytoplasmic side - so the term is not wrong. It is simply too broad: the informative statement about the non-membrane-bound pool is cytosol, which Reactome already annotates ten times on this gene, and the membrane-associated pool is covered by the Golgi, TGN and vesicle-membrane rows. Tracing the cited rule also failed (see propagation_review), which is a further reason not to lean on this row for anything. human/AP1S3 GO:0032588 trans-Golgi network membrane ARBA:ARBA00033972 ACCEPT specific (1-20) 2 human/AP2M1 GO:0031623 receptor internalization ARBA:ARBA00087457 ACCEPT specific (1-20) 13 human/AP2M1 GO:0099003 vesicle-mediated transport in synapse ARBA:ARBA00027531 ACCEPT general (21-200) 31 human/AP3B2 GO:0097708 intracellular vesicle ARBA:ARBA00027639 ACCEPT very general (>200 descendants) 276 human/AP3D1 GO:0005794 Golgi apparatus ARBA:ARBA00028708 KEEP_AS_NON_CORE general (21-200) 48 human/AP3D1 GO:0007041 lysosomal transport ARBA:ARBA00033548 KEEP_AS_NON_CORE general (21-200) 21 human/AP3D1 GO:0010496 intercellular transport ARBA:ARBA00092758 REMOVE specific (1-20) 3 TERM_MISREAD wrong manual TERM_MISREAD GO:0010496 is defined as the movement of substances between cells. Nothing in the AP-3 literature has AP3D1 transferring material from one cell to another; every characterised cargo (LAMP1/LAMP2, CD63, tyrosinase, VAMP7, ZnT2/ZnT3, PI4KIIalpha, CLN3) moves between intracellular compartments of the same cell. I fetched ARBA00092758 and evaluated all 99 condition sets against AP3D1's complete signature complement: exactly one is satisfied, a bare 'FunFam 3.30.450.50:FF:000001' with no taxon guard - the same AP3D1-specific FunFam that correctly yields 'lysosomal transport' and 'endosome membrane' under other rules. The identical evidence therefore produces a term with the wrong topology. This is the one electronic row here removed on a positive biological argument rather than for generality. human/AP3D1 GO:0016050 vesicle organization ARBA:ARBA00028845 KEEP_AS_NON_CORE general (21-200) 99 human/AP3D1 GO:0032502 developmental process ARBA:ARBA00028739 MARK_AS_OVER_ANNOTATED very general (>200 descendants) 4075 TOO_GENERAL true but uninformative root ARBA00028739 has 893 condition sets and AP3D1 satisfies none of them: no set names PTHR22781, and none of AP3D1's three FunFams (1.25.10.10:FF:000785, 1.25.10.10:FF:000808, 3.30.450.50:FF:000001) appears. I am not claiming the annotation is biologically false - HPS10 patients do have neurodevelopmental delay - only that the published rule cannot be shown to produce it, and that 'developmental process' is one step below the biological_process root and tells a reader nothing. The same provenance gap has been recorded for other ARBA rules in this repository. human/AP3M1 GO:0005737 cytoplasm ARBA:ARBA00026971 KEEP_AS_NON_CORE very general (>200 descendants) 1146 human/AP3M2 GO:0005737 cytoplasm ARBA:ARBA00026971 ACCEPT very general (>200 descendants) 1146 human/AP4B1 GO:0008104 intracellular protein localization ARBA:ARBA00028253 ACCEPT very general (>200 descendants) 356 human/AP4E1 GO:0005768 endosome ARBA:ARBA00028568 UNDECIDED general (21-200) 68 human/AP4E1 GO:0005802 trans-Golgi network ARBA:ARBA00029112 MODIFY specific (1-20) 3 NEEDS_MORE_SPECIFIC true but uninformative replacement term Human biochemical evidence places AP-4 on the cytoplasmic face of the TGN, where ARF1 recruits the epsilon-containing complex. The peripheral membrane pool is more precise than the broad compartment; this does not imply epsilon spans the bilayer. human/AP4E1 GO:0008104 intracellular protein localization ARBA:ARBA00028253 ACCEPT very general (>200 descendants) 356 human/AP4E1 GO:0045184 establishment of protein localization ARBA:ARBA00027110 ACCEPT general (21-200) 176 human/AP4M1 GO:0005737 cytoplasm ARBA:ARBA00026971 KEEP_AS_NON_CORE very general (>200 descendants) 1146 human/AP4S1 GO:0005737 cytoplasm ARBA:ARBA00026971 ACCEPT very general (>200 descendants) 1146 human/AP4S1 GO:0012505 endomembrane system ARBA:ARBA00028953 MODIFY very general (>200 descendants) 357 NEEDS_MORE_SPECIFIC true but uninformative replacement term This is the textbook too-general case. The gene already holds GO:0005802 trans-Golgi network by NAS and GO:0032588 trans-Golgi network membrane twice by TAS, all of which the endomembrane system term subsumes, and UniProt's own curated location line names the TGN membrane. Replacing it with GO:0032588 keeps the (correct) claim and states it at the grain the evidence actually supports. Note for anyone consuming this: GO:0032588 is already on the gene twice by TAS, so the replacement term is not new and the practical effect is the removal of a redundant parent, not the creation of a third GO:0032588 row. As with the other ARBA row, the rule's published condition sets do not fire on this protein's real InterPro matches, which is recorded in the propagation review; the replacement is proposed on grounds of specificity, not on that provenance issue. human/APAF1 GO:0006915 apoptotic process ARBA:ARBA00027755 MODIFY general (21-200) 115 NEEDS_MORE_SPECIFIC true but uninformative replacement term APAF1 acts after mitochondrial cytochrome c release as the scaffold that nucleates procaspase-9 activation in the intrinsic pathway, not as a generic apoptotic-process or apoptotic-regulation factor. human/APAF1 GO:0048731 system development ARBA:ARBA00027702 MARK_AS_OVER_ANNOTATED very general (>200 descendants) 2438 TOO_GENERAL true but uninformative more specific Loss of APAF1 can alter developmental or stress-response cell death outcomes, but APAF1 does the direct work of cytochrome-c-dependent apoptosome assembly in intrinsic apoptotic signaling. The more specific stimulus and anatomy terms should not be the core flat APAF1 process annotations. human/APAF1 GO:0160108 animal gross anatomical part developmental process ARBA:ARBA00098139 MARK_AS_OVER_ANNOTATED very general (>200 descendants) 3010 TOO_GENERAL true but uninformative more specific Loss of APAF1 can alter developmental or stress-response cell death outcomes, but APAF1 does the direct work of cytochrome-c-dependent apoptosome assembly in intrinsic apoptotic signaling. The more specific stimulus and anatomy terms should not be the core flat APAF1 process annotations. human/APC GO:0005634 nucleus ARBA:ARBA00026330 ACCEPT very general (>200 descendants) 473 human/APC GO:0008285 negative regulation of cell population proliferation ARBA:ARBA00027539 KEEP_AS_NON_CORE general (21-200) 81 human/APC GO:0015630 microtubule cytoskeleton ARBA:ARBA00029268 ACCEPT general (21-200) 108 human/APC GO:0016342 catenin complex ARBA:ARBA00086680 UNDECIDED leaf (0) 0 human/APC GO:0030054 cell junction ARBA:ARBA00028333 ACCEPT general (21-200) 189 human/APC GO:0031256 leading edge membrane ARBA:ARBA00086462 ACCEPT specific (1-20) 8 human/APC GO:0090090 negative regulation of canonical Wnt signaling pathway ARBA:ARBA00027950 ACCEPT leaf (0) 0 human/APC GO:0120025 plasma membrane bounded cell projection ARBA:ARBA00028036 ACCEPT very general (>200 descendants) 303 human/APC2 GO:0015630 microtubule cytoskeleton ARBA:ARBA00029268 ACCEPT general (21-200) 108 human/APC2 GO:0016342 catenin complex ARBA:ARBA00086680 UNDECIDED leaf (0) 0 human/APC2 GO:0031256 leading edge membrane ARBA:ARBA00086462 KEEP_AS_NON_CORE specific (1-20) 8 human/APC2 GO:0090090 negative regulation of canonical Wnt signaling pathway ARBA:ARBA00027950 ACCEPT leaf (0) 0 human/APC2 GO:0120025 plasma membrane bounded cell projection ARBA:ARBA00028036 KEEP_AS_NON_CORE very general (>200 descendants) 303 human/APH1A GO:0006508 proteolysis ARBA:ARBA00026291 MODIFY general (21-200) 45 NEEDS_MORE_SPECIFIC true but uninformative replacement term Replace the broad proteolysis term with the more specific regulated intramembrane-processing terms supported for gamma-secretase. human/APH1A GO:0070765 gamma-secretase complex ARBA:ARBA00049824 ACCEPT leaf (0) 0 human/APH1B GO:0006508 proteolysis ARBA:ARBA00026291 MODIFY general (21-200) 45 NEEDS_MORE_SPECIFIC true but uninformative replacement term Replace the broad proteolysis term with regulated intramembrane substrate-processing terms supported for gamma-secretase. human/APH1B GO:0070765 gamma-secretase complex ARBA:ARBA00049824 ACCEPT leaf (0) 0 human/API5 GO:0043066 negative regulation of apoptotic process ARBA:ARBA00027746 ACCEPT general (21-200) 79 human/APLP1 GO:0007399 nervous system development ARBA:ARBA00027428 KEEP_AS_NON_CORE very general (>200 descendants) 913 human/APLP1 GO:0048513 animal organ development ARBA:ARBA00029247 MARK_AS_OVER_ANNOTATED very general (>200 descendants) 1888 UNCLASSIFIED unclassified The available literature focuses on gene structure and brain expression, not organ development. human/APLP2 GO:0031091 platelet alpha granule ARBA:ARBA00084785 KEEP_AS_NON_CORE specific (1-20) 2 human/APOB GO:0006629 lipid metabolic process ARBA:ARBA00028591 ACCEPT very general (>200 descendants) 608 human/APP GO:0010604 positive regulation of macromolecule metabolic process ARBA:ARBA00026482 MARK_AS_OVER_ANNOTATED very general (>200 descendants) 467 TOO_GENERAL true but uninformative broad Too broad to be informative. Over-annotation. human/APP GO:0031091 platelet alpha granule ARBA:ARBA00084785 ACCEPT specific (1-20) 2 human/APP GO:0043005 neuron projection ARBA:ARBA00027418 ACCEPT general (21-200) 135 human/APP GO:0051246 regulation of protein metabolic process ARBA:ARBA00028884 MARK_AS_OVER_ANNOTATED very general (>200 descendants) 442 TOO_GENERAL true but uninformative broad Too broad to be informative. Over-annotation. human/APP GO:0140677 molecular function activator activity ARBA:ARBA00034589 MARK_AS_OVER_ANNOTATED general (21-200) 104 TOO_GENERAL true but uninformative broad Too broad to be informative. Over-annotation. human/APPL2 GO:0001786 phosphatidylserine binding ARBA:ARBA00089669 KEEP_AS_NON_CORE leaf (0) 0 human/APPL2 GO:0005768 endosome ARBA:ARBA00028568 ACCEPT general (21-200) 68 human/APPL2 GO:0006606 protein import into nucleus ARBA:ARBA00028627 KEEP_AS_NON_CORE specific (1-20) 2 human/APPL2 GO:0007179 transforming growth factor beta receptor signaling pathway ARBA:ARBA00085361 KEEP_AS_NON_CORE specific (1-20) 1 human/APPL2 GO:0030659 cytoplasmic vesicle membrane ARBA:ARBA00026540 KEEP_AS_NON_CORE general (21-200) 107 human/APPL2 GO:0035091 phosphatidylinositol binding ARBA:ARBA00026346 ACCEPT leaf (0) 0 human/APPL2 GO:0042592 homeostatic process ARBA:ARBA00027526 MARK_AS_OVER_ANNOTATED very general (>200 descendants) 255 TOO_GENERAL true but uninformative general ARBA00027526 has 135 condition sets covering bacteria, fungi, plants and metazoa. APPL2 does act in homeostasis - glucose homeostasis and adaptive thermogenesis are both annotated - but those specific rows are what carry the claim. A rule this promiscuous attached to a term this general is the clearest over-annotation in the record. human/APPL2 GO:0098588 bounding membrane of organelle ARBA:ARBA00027281 MARK_AS_OVER_ANNOTATED very general (>200 descendants) 201 TOO_GENERAL true but uninformative broad ARBA00027281 has 171 condition sets spanning bacteria, plants, fungi and metazoa. 'Bounding membrane of organelle' is a structural-class term that applies to any peripheral membrane protein on any organelle; combined with a rule that broad it conveys nothing about APPL2 that the endosome-membrane and phagosome-membrane rows do not say better. human/APPL2 GO:2000045 regulation of G1/S transition of mitotic cell cycle ARBA:ARBA00033889 KEEP_AS_NON_CORE specific (1-20) 6 human/APRT GO:1901363 heterocyclic compound binding ARBA:ARBA00027813 MARK_AS_OVER_ANNOTATED general (21-200) 114 TOO_GENERAL true but uninformative generic The term is not incorrect (adenine and AMP are heterocyclic), but it is an overly generic parent term that adds no functional information beyond the specific substrate/product binding terms; per curation guidelines uninformative high-level binding terms should not be treated as representing gene function. human/AR GO:0003707 nuclear steroid receptor activity ARBA:ARBA00089151 ACCEPT specific (1-20) 3 human/AR GO:0033574 response to testosterone ARBA:ARBA00085129 ACCEPT specific (1-20) 1 human/AR GO:1990837 sequence-specific double-stranded DNA binding ARBA:ARBA00028376 ACCEPT general (21-200) 48 human/ARAF GO:0043066 negative regulation of apoptotic process ARBA:ARBA00027746 KEEP_AS_NON_CORE general (21-200) 79 human/ARFGEF1 GO:0006887 exocytosis ARBA:ARBA00027178 MARK_AS_OVER_ANNOTATED general (21-200) 44 WRONG_LOCATION wrong integral membrane GO:0006887 is defined as a secretion process that ends when molecules are secreted from the cell. BIG1 demonstrated territory is upstream of that - the trans-Golgi network and endosomes. Where BIG1 has been implicated in surface delivery the cargo is an integral membrane protein, ABCA1 or GABA-A receptors, which is Golgi-to-plasma-membrane transport, a sibling process that by its own definition precedes exocytosis. The supported level is GO:0016192 vesicle-mediated transport, which this record already carries by IBA, so no replacement term is proposed. human/ARFGEF1 GO:0010256 endomembrane system organization ARBA:ARBA00026889 ACCEPT general (21-200) 139 human/ARFGEF1 GO:0034237 protein kinase A regulatory subunit binding ARBA:ARBA00090632 ACCEPT leaf (0) 0 human/ARFGEF2 GO:0010256 endomembrane system organization ARBA:ARBA00026889 ACCEPT general (21-200) 139 human/ARFGEF2 GO:0034237 protein kinase A regulatory subunit binding ARBA:ARBA00090632 ACCEPT leaf (0) 0 human/ARG1 GO:0042127 regulation of cell population proliferation ARBA:ARBA00027546 KEEP_AS_NON_CORE very general (>200 descendants) 258 human/ARHGAP29 GO:0005829 cytosol ARBA:ARBA00029243 ACCEPT general (21-200) 73 human/ARHGAP29 GO:0051056 regulation of small GTPase mediated signal transduction ARBA:ARBA00027280 ACCEPT general (21-200) 24 human/ARHGEF16 GO:0005829 cytosol ARBA:ARBA00029243 KEEP_AS_NON_CORE general (21-200) 73 human/ARHGEF26 GO:0005829 cytosol ARBA:ARBA00029243 KEEP_AS_NON_CORE general (21-200) 73 human/ARHGEF3 GO:0005829 cytosol ARBA:ARBA00029243 KEEP_AS_NON_CORE general (21-200) 73 human/ARHGEF3 GO:0051056 regulation of small GTPase mediated signal transduction ARBA:ARBA00027280 KEEP_AS_NON_CORE general (21-200) 24 human/ARHGEF4 GO:0005829 cytosol ARBA:ARBA00029243 KEEP_AS_NON_CORE general (21-200) 73 human/ARHGEF4 GO:0030032 lamellipodium assembly ARBA:ARBA00086196 KEEP_AS_NON_CORE specific (1-20) 1 human/ARHGEF4 GO:0046847 filopodium assembly ARBA:ARBA00085124 MARK_AS_OVER_ANNOTATED specific (1-20) 1 UNCLASSIFIED unclassified "[PMID:17599059 ""Consistent with this, either Asef2-DeltaABR/SH3 or Asef2 plus truncated mutant APC stimulated lamellipodia formation in MDCK cells and filopodia formation in HeLa cells.""]" human/ARHGEF4 GO:0051056 regulation of small GTPase mediated signal transduction ARBA:ARBA00027280 MODIFY general (21-200) 24 NEEDS_MORE_SPECIFIC true but uninformative replacement term "[PMID:17704816 ""Here we show that binding of the armadillo repeats of APC to a 'core APC-binding' (CAB) motif within ASEF, or truncation of the SH3 domain of ASEF, relieves autoinhibition, allowing the specific activation of CDC42.""] [PMID:17214551 ""Here we investigated the specificity and regulation of Asef by measuring its GEF activity in vitro and observed hardly any activity towards Rac1, Rac2 and Rac3, or RhoA and TC10. In contrast, various purified Asef protein fragments catalyzed the nucleotide exchange reaction of Cdc42.""]" human/ARHGEF9 GO:0005829 cytosol ARBA:ARBA00029243 ACCEPT general (21-200) 73 human/ARHGEF9 GO:0051056 regulation of small GTPase mediated signal transduction ARBA:ARBA00027280 MODIFY general (21-200) 24 NEEDS_MORE_SPECIFIC true but uninformative replacement term The human hPEM-2 study reports selective cellular activation of CDC42 rather than Rac or RhoA. Exchange-factor activity performs the nucleotide-switch regulatory step, supporting the CDC42-specific child term. The complete historical ARBA rule remains uninspected; this refinement rests on independent target evidence. The gephyrin adaptor activity is not assumed to require CDC42 exchange. human/ARL13A GO:0097731 9+0 non-motile cilium ARBA:ARBA00026429 KEEP_AS_NON_CORE specific (1-20) 13 human/ARL2BP GO:0005739 mitochondrion ARBA:ARBA00026962 ACCEPT general (21-200) 70 human/ARL6 GO:0061512 protein localization to cilium ARBA:ARBA00091714 ACCEPT specific (1-20) 8 human/ARL8A GO:0051233 spindle midzone ARBA:ARBA00089348 KEEP_AS_NON_CORE specific (1-20) 2 human/ARL8B GO:0051233 spindle midzone ARBA:ARBA00089348 KEEP_AS_NON_CORE specific (1-20) 2 human/ARMC10 GO:0005739 mitochondrion ARBA:ARBA00026962 ACCEPT general (21-200) 70 human/ARMCX6 GO:0005737 cytoplasm ARBA:ARBA00026971 KEEP_AS_NON_CORE very general (>200 descendants) 1146 human/ARNT GO:0001666 response to hypoxia ARBA:ARBA00027678 ACCEPT specific (1-20) 8 human/ARSB GO:0004065 arylsulfatase activity ARBA:ARBA00087504 KEEP_AS_NON_CORE leaf (0) 0 human/ARSI GO:0004065 arylsulfatase activity ARBA:ARBA00087504 MODIFY leaf (0) 0 OTHER_TERM different term needed replacement term ARSI does hydrolyze the artificial aryl substrate 4-MUS, but the 2026 natural-substrate study supports the more biologically informative GO:0003943 N-acetylgalactosamine-4-sulfatase activity. human/ARSJ GO:0004065 arylsulfatase activity ARBA:ARBA00087504 MODIFY leaf (0) 0 TOO_SPECIFIC overreach replacement term ARSJ-specific cleavage of an aryl sulfate has not been demonstrated, and the available literature reports no detectable activity when recombinant ARSJ was tested in the standard arylsulfatase assay. Family conservation supports only the broader sulfuric ester hydrolase activity until a substrate is identified. human/ARSL GO:0005788 endoplasmic reticulum lumen ARBA:ARBA00028691 KEEP_AS_NON_CORE specific (1-20) 9 human/ARV1 GO:0005783 endoplasmic reticulum ARBA:ARBA00028672 ACCEPT general (21-200) 100 human/ARX GO:0030182 neuron differentiation ARBA:ARBA00027575 ACCEPT very general (>200 descendants) 323 human/ARX GO:1990837 sequence-specific double-stranded DNA binding ARBA:ARBA00028376 ACCEPT general (21-200) 48 human/ASAH2 GO:0005737 cytoplasm ARBA:ARBA00026971 KEEP_AS_NON_CORE very general (>200 descendants) 1146 human/ASAH2 GO:0046512 sphingosine biosynthetic process ARBA:ARBA00027422 ACCEPT leaf (0) 0 human/ASAH2 GO:0046513 ceramide biosynthetic process ARBA:ARBA00027419 ACCEPT specific (1-20) 6 human/ASAH2B GO:0005737 cytoplasm ARBA:ARBA00026971 UNDECIDED very general (>200 descendants) 1146 human/ASAH2B GO:0005886 plasma membrane ARBA:ARBA00027801 UNDECIDED very general (>200 descendants) 415 human/ASAH2B GO:0046512 sphingosine biosynthetic process ARBA:ARBA00027422 REMOVE leaf (0) 0 NONCATALYTIC_HOMOLOG wrong manual NONCATALYTIC_HOMOLOG "[file:human/ASAH2B/ASAH2B-bioinformatics/RESULTS.md ""Active site ASAH2 S354 (Nucleophile): outside aligned region""] [file:human/ASAH2B/ASAH2B-uniprot.txt ""DE RecName: Full=Putative inactive neutral ceramidase B {ECO:0000305};""]" human/ASAH2B GO:0046513 ceramide biosynthetic process ARBA:ARBA00027419 REMOVE specific (1-20) 6 NONCATALYTIC_HOMOLOG wrong manual NONCATALYTIC_HOMOLOG "[file:human/ASAH2B/ASAH2B-bioinformatics/RESULTS.md ""Active site ASAH2 S354 (Nucleophile): outside aligned region""] [file:human/ASAH2B/ASAH2B-uniprot.txt ""DE RecName: Full=Putative inactive neutral ceramidase B {ECO:0000305};""]" human/ASB10 GO:0005829 cytosol ARBA:ARBA00029243 ACCEPT general (21-200) 73 human/ASB11 GO:0005829 cytosol ARBA:ARBA00029243 ACCEPT general (21-200) 73 human/ASB13 GO:0005829 cytosol ARBA:ARBA00029243 ACCEPT general (21-200) 73 human/ASB14 GO:0005829 cytosol ARBA:ARBA00029243 KEEP_AS_NON_CORE general (21-200) 73 human/ASB16 GO:0005829 cytosol ARBA:ARBA00029243 KEEP_AS_NON_CORE general (21-200) 73 human/ASB18 GO:0005829 cytosol ARBA:ARBA00029243 KEEP_AS_NON_CORE general (21-200) 73 human/ASB2 GO:0000151 ubiquitin ligase complex ARBA:ARBA00029181 MODIFY general (21-200) 52 NEEDS_MORE_SPECIFIC true but uninformative replacement term "[PMID:15590664 ""Here we show that ASB2, by interacting with the Elongin BC complex, can assemble with Cullin5.Rbx1 to form an E3 ubiquitin ligase complex that stimulates polyubiquitination by the E2 ubiquitin-conjugating enzyme Ubc5.""] [PMID:15590664 ""This is a first indication that a member of the ASB protein family, ASB2, is a subunit of an ECS (Elongin C-Cullin-SOCS box)-type E3 ubiquitin ligase complex.""]" human/ASB2 GO:0005829 cytosol ARBA:ARBA00029243 ACCEPT general (21-200) 73 human/ASB2 GO:0055007 cardiac muscle cell differentiation ARBA:ARBA00084649 KEEP_AS_NON_CORE general (21-200) 29 human/ASB3 GO:0005829 cytosol ARBA:ARBA00029243 ACCEPT general (21-200) 73 human/ASB4 GO:0005829 cytosol ARBA:ARBA00029243 ACCEPT general (21-200) 73 human/ASB4 GO:0031462 Cul2-RING ubiquitin ligase complex ARBA:ARBA00085912 ACCEPT leaf (0) 0 human/ASB4 GO:0031466 Cul5-RING ubiquitin ligase complex ARBA:ARBA00085916 ACCEPT leaf (0) 0 human/ASB5 GO:0005829 cytosol ARBA:ARBA00029243 KEEP_AS_NON_CORE general (21-200) 73 human/ASB6 GO:0005829 cytosol ARBA:ARBA00029243 ACCEPT general (21-200) 73 human/ASB8 GO:0005829 cytosol ARBA:ARBA00029243 KEEP_AS_NON_CORE general (21-200) 73 human/ASB9 GO:0005829 cytosol ARBA:ARBA00029243 ACCEPT general (21-200) 73 human/ASCC3 GO:0004386 helicase activity ARBA:ARBA00026537 MODIFY specific (1-20) 14 NEEDS_MORE_SPECIFIC true but uninformative replacement term ASCC3 is a helicase-family ATPase, but GOA already has stronger, more specific annotations for 3'-5' DNA helicase activity and ATP hydrolysis activity. The generic helicase term should not be the preferred assertion. human/ASCC3 GO:0180022 RQC-trigger complex ARBA:ARBA00091275 ACCEPT leaf (0) 0 human/ASCL1 GO:0070888 E-box binding ARBA:ARBA00086501 ACCEPT leaf (0) 0 human/ASH1L GO:0031981 nuclear lumen ARBA:ARBA00026536 ACCEPT general (21-200) 139 human/ASH1L GO:0046975 histone H3K36 methyltransferase activity ARBA:ARBA00027571 MODIFY specific (1-20) 2 NEEDS_MORE_SPECIFIC true but uninformative replacement term The K36-specific inference agrees with direct human assays in PMID:26002201. GO:0140954 covers successive mono- and dimethylation of initially unmethylated H3K36, matching the measured product states. human/ASPM GO:0007051 spindle organization ARBA:ARBA00043498 ACCEPT general (21-200) 36 human/ASPN GO:0140150 gel phase of interstitial matrix ARBA:ARBA00096892 MARK_AS_OVER_ANNOTATED leaf (0) 0 UNCLASSIFIED unclassified "[file:human/ASPN/ASPN-uniprot.txt ""CC attachment of O-linked glycosaminoglycans and this is probably not a""] [PMID:19589127 ""Here, we show that asporin binds collagen type I.""]" human/ASPRV1 GO:0016485 protein processing ARBA:ARBA00028812 ACCEPT general (21-200) 30 human/ASTE1 GO:0004520 DNA endonuclease activity ARBA:ARBA00029205 ACCEPT general (21-200) 28 human/ASTE1 GO:0006310 DNA recombination ARBA:ARBA00028026 KEEP_AS_NON_CORE general (21-200) 85 human/ASZ1 GO:0036464 cytoplasmic ribonucleoprotein granule ARBA:ARBA00026950 ACCEPT specific (1-20) 14 human/ATAD1 GO:0016020 membrane ARBA:ARBA00028763 MODIFY very general (>200 descendants) 895 NEEDS_MORE_SPECIFIC true but uninformative replacement term Replace the generic membrane annotation with the specific experimentally supported membrane locations. human/ATF3 GO:1990837 sequence-specific double-stranded DNA binding ARBA:ARBA00028376 ACCEPT general (21-200) 48 human/ATF4 GO:0042981 regulation of apoptotic process ARBA:ARBA00027086 KEEP_AS_NON_CORE very general (>200 descendants) 218 human/ATF5 GO:0042981 regulation of apoptotic process ARBA:ARBA00027086 KEEP_AS_NON_CORE very general (>200 descendants) 218 human/ATF6 GO:0036500 ATF6-mediated unfolded protein response ARBA:ARBA00091677 ACCEPT leaf (0) 0 human/ATF6 GO:1903891 regulation of ATF6-mediated unfolded protein response ARBA:ARBA00092211 MODIFY specific (1-20) 2 TOO_SPECIFIC overreach replacement term The demonstrated activity is execution of the ATF6 response through ERSE-dependent chaperone-gene transcription. The human ATF6 overexpression result in PMID:9837962 establishes this transcriptional output, but does not by itself distinguish an additional regulatory step acting on the ATF6 pathway. GO:0036500 explicitly includes signaling through its downstream transcriptional endpoint and is the better-supported term. This precision change does not assert that a pathway component can never regulate its own pathway or that an unread part of the original paper contains no such mechanism; the original evidence code and source are preserved. human/ATG12 GO:0006914 autophagy ARBA:ARBA00027757 ACCEPT general (21-200) 49 human/ATG12 GO:0032991 protein-containing complex ARBA:ARBA00028902 ACCEPT very general (>200 descendants) 2083 human/ATG13 GO:0042127 regulation of cell population proliferation ARBA:ARBA00027546 KEEP_AS_NON_CORE very general (>200 descendants) 258 human/ATG14 GO:0032991 protein-containing complex ARBA:ARBA00028902 MODIFY very general (>200 descendants) 2083 NEEDS_MORE_SPECIFIC true but uninformative replacement term Modify to PI3KC3-C1/type I class III PI3K complex. ATG14 is specifically the autophagy-directed regulatory subunit of PI3KC3-C1 rather than merely part of an unspecified protein complex. human/ATG16L1 GO:0034497 protein localization to phagophore assembly site ARBA:ARBA00092844 ACCEPT leaf (0) 0 human/ATG16L1 GO:0042802 identical protein binding ARBA:ARBA00027930 KEEP_AS_NON_CORE specific (1-20) 1 human/ATG16L2 GO:0034274 Atg12-Atg5-Atg16 complex ARBA:ARBA00033810 ACCEPT leaf (0) 0 human/ATG5 GO:0043069 negative regulation of programmed cell death ARBA:ARBA00027748 KEEP_AS_NON_CORE general (21-200) 89 human/ATG7 GO:0009896 positive regulation of catabolic process ARBA:ARBA00028093 ACCEPT general (21-200) 120 human/ATG7 GO:0031667 response to nutrient levels ARBA:ARBA00034581 ACCEPT general (21-200) 126 human/ATG7 GO:0042981 regulation of apoptotic process ARBA:ARBA00027086 KEEP_AS_NON_CORE very general (>200 descendants) 218 human/ATG7 GO:0060255 regulation of macromolecule metabolic process ARBA:ARBA00027781 KEEP_AS_NON_CORE very general (>200 descendants) 1504 human/ATG7 GO:0080090 regulation of primary metabolic process ARBA:ARBA00026284 KEEP_AS_NON_CORE very general (>200 descendants) 1424 human/ATL1 GO:0016320 endoplasmic reticulum membrane fusion ARBA:ARBA00093706 ACCEPT leaf (0) 0 human/ATL1 GO:0098826 endoplasmic reticulum tubular network membrane ARBA:ARBA00091231 ACCEPT specific (1-20) 1 human/ATL1 GO:0140523 GTPase-dependent fusogenic activity ARBA:ARBA00093704 ACCEPT leaf (0) 0 human/ATL1 GO:1990809 endoplasmic reticulum tubular network membrane organization ARBA:ARBA00093725 ACCEPT leaf (0) 0 human/ATL3 GO:0016320 endoplasmic reticulum membrane fusion ARBA:ARBA00093706 ACCEPT leaf (0) 0 human/ATL3 GO:0098826 endoplasmic reticulum tubular network membrane ARBA:ARBA00091231 ACCEPT specific (1-20) 1 human/ATL3 GO:0140523 GTPase-dependent fusogenic activity ARBA:ARBA00093704 ACCEPT leaf (0) 0 human/ATL3 GO:1990809 endoplasmic reticulum tubular network membrane organization ARBA:ARBA00093725 ACCEPT leaf (0) 0 human/ATM GO:0000077 DNA damage checkpoint signaling ARBA:ARBA00090214 ACCEPT specific (1-20) 4 human/ATM GO:0000724 double-strand break repair via homologous recombination ARBA:ARBA00027336 ACCEPT specific (1-20) 14 human/ATM GO:0007127 meiosis I ARBA:ARBA00028964 UNDECIDED general (21-200) 44 human/ATM GO:0010212 response to ionizing radiation ARBA:ARBA00090590 ACCEPT specific (1-20) 5 human/ATM GO:0010468 regulation of gene expression ARBA:ARBA00028334 KEEP_AS_NON_CORE very general (>200 descendants) 874 human/ATM GO:0032210 regulation of telomere maintenance via telomerase ARBA:ARBA00047237 ACCEPT specific (1-20) 2 human/ATM GO:0043065 positive regulation of apoptotic process ARBA:ARBA00027745 KEEP_AS_NON_CORE general (21-200) 68 human/ATM GO:0080135 regulation of cellular response to stress ARBA:ARBA00026867 KEEP_AS_NON_CORE general (21-200) 167 human/ATM GO:1901701 cellular response to oxygen-containing compound ARBA:ARBA00027483 KEEP_AS_NON_CORE very general (>200 descendants) 308 human/ATM GO:1904358 positive regulation of telomere maintenance via telomere lengthening ARBA:ARBA00047255 ACCEPT specific (1-20) 1 human/ATOH1 GO:0048731 system development ARBA:ARBA00027702 MARK_AS_OVER_ANNOTATED very general (>200 descendants) 2438 TOO_GENERAL true but uninformative More informative The term is not false, but it obscures ATOH1's specific roles in neural, sensory, and epithelial lineage differentiation. More informative processes are already present, so this generic parent adds little biological value. human/ATP13A3 GO:0015417 ABC-type polyamine transporter activity ARBA:ARBA00098143 MODIFY specific (1-20) 1 TOO_SPECIFIC overreach replacement term The ARBA assignment has a mechanistic mismatch. The current term belongs to the ABC transporter lineage, whose definition specifies ABC nucleotide-binding/transmembrane architecture. ATP13A3 is a P5B-type ATPase. The supported substrate-transport function is retained using the existing mechanism-neutral polyamine transporter term, while the P-type mechanism is represented by its separate existing annotation. Preserve the original source ID and evidence code. human/ATP1A1 GO:0005890 sodium:potassium-exchanging ATPase complex ARBA:ARBA00088151 ACCEPT leaf (0) 0 human/ATP1A1 GO:0006883 intracellular sodium ion homeostasis ARBA:ARBA00086918 ACCEPT leaf (0) 0 human/ATP1A1 GO:0030007 intracellular potassium ion homeostasis ARBA:ARBA00086105 ACCEPT leaf (0) 0 human/ATP1A1 GO:0036376 sodium ion export across plasma membrane ARBA:ARBA00089462 ACCEPT leaf (0) 0 human/ATP1A1 GO:0051087 protein-folding chaperone binding ARBA:ARBA00088077 KEEP_AS_NON_CORE specific (1-20) 1 human/ATP1A1 GO:0086064 cell communication by electrical coupling involved in cardiac conduction ARBA:ARBA00098243 MARK_AS_OVER_ANNOTATED specific (1-20) 11 INDIRECT_EFFECT overreach secondary The annotation is too specific for the established pump/contractility evidence. GO:0086064 concerns current passing between adjacent cytoplasms through intercellular protein channels. The cited mouse beta1-knockout paper measures secondary alpha1 reduction, pump activity and cardiac calcium/contractile physiology, not that intercellular step. This is a process-scope overannotation, not a title-based beta1 misattribution or a denial of ATP1A1 cardiac relevance. Preserve the original TAS/ARBA assertions and do not manufacture a new process. human/ATP1A1 GO:1990573 potassium ion import across plasma membrane ARBA:ARBA00090368 ACCEPT leaf (0) 0 human/ATP1A2 GO:0005737 cytoplasm ARBA:ARBA00026971 KEEP_AS_NON_CORE very general (>200 descendants) 1146 human/ATP1A2 GO:0006942 regulation of striated muscle contraction ARBA:ARBA00087049 KEEP_AS_NON_CORE general (21-200) 41 human/ATP1A2 GO:0007154 cell communication ARBA:ARBA00028945 KEEP_AS_NON_CORE very general (>200 descendants) 1207 human/ATP1A2 GO:0008015 blood circulation ARBA:ARBA00029044 KEEP_AS_NON_CORE general (21-200) 169 human/ATP1A2 GO:0008016 regulation of heart contraction ARBA:ARBA00093015 KEEP_AS_NON_CORE general (21-200) 111 human/ATP1A2 GO:0030003 intracellular monoatomic cation homeostasis ARBA:ARBA00028070 ACCEPT general (21-200) 75 human/ATP1A3 GO:0005890 sodium:potassium-exchanging ATPase complex ARBA:ARBA00088151 ACCEPT leaf (0) 0 human/ATP1A3 GO:0006883 intracellular sodium ion homeostasis ARBA:ARBA00086918 ACCEPT leaf (0) 0 human/ATP1A3 GO:0030007 intracellular potassium ion homeostasis ARBA:ARBA00086105 ACCEPT leaf (0) 0 human/ATP1A3 GO:0036376 sodium ion export across plasma membrane ARBA:ARBA00089462 ACCEPT leaf (0) 0 human/ATP1A3 GO:0051087 protein-folding chaperone binding ARBA:ARBA00088077 KEEP_AS_NON_CORE specific (1-20) 1 human/ATP1A3 GO:0086064 cell communication by electrical coupling involved in cardiac conduction ARBA:ARBA00098243 MARK_AS_OVER_ANNOTATED specific (1-20) 11 UNCLASSIFIED unclassified GO0086064 specifically requires current transfer between adjacent cell cytoplasms through intercellular channels. Alpha3 maintains ionic gradients, but the inspected cardiac evidence concerns pump abundance, contractility and calcium transients rather than that intercellular coupling step. The ARBA propagation is too specific; this does not deny a role in excitability. human/ATP1A3 GO:1990573 potassium ion import across plasma membrane ARBA:ARBA00090368 ACCEPT leaf (0) 0 human/ATP2B2 GO:0098982 GABA-ergic synapse ARBA:ARBA00027096 UNDECIDED specific (1-20) 1 human/ATP2B2 GO:1903779 regulation of cardiac conduction ARBA:ARBA00091800 UNDECIDED specific (1-20) 5 human/ATP5F1A GO:0016469 proton-transporting two-sector ATPase complex ARBA:ARBA00028662 ACCEPT specific (1-20) 16 human/ATP5F1A GO:1902495 transmembrane transporter complex ARBA:ARBA00026587 ACCEPT general (21-200) 94 human/ATP5F1B GO:0005737 cytoplasm ARBA:ARBA00026971 ACCEPT very general (>200 descendants) 1146 human/ATP5F1B GO:0016469 proton-transporting two-sector ATPase complex ARBA:ARBA00028662 ACCEPT specific (1-20) 16 human/ATP5F1B GO:1902495 transmembrane transporter complex ARBA:ARBA00026587 ACCEPT general (21-200) 94 human/ATP5MC1 GO:0005743 mitochondrial inner membrane ARBA:ARBA00028608 ACCEPT general (21-200) 23 human/ATP5MC2 GO:0005743 mitochondrial inner membrane ARBA:ARBA00028608 ACCEPT general (21-200) 23 human/ATP5MC3 GO:0005743 mitochondrial inner membrane ARBA:ARBA00028608 ACCEPT general (21-200) 23 human/ATP5ME GO:0016020 membrane ARBA:ARBA00028763 ACCEPT very general (>200 descendants) 895 human/ATP6AP1 GO:0012505 endomembrane system ARBA:ARBA00028953 KEEP_AS_NON_CORE very general (>200 descendants) 357 human/ATP6AP1 GO:0030659 cytoplasmic vesicle membrane ARBA:ARBA00026540 KEEP_AS_NON_CORE general (21-200) 107 human/ATP6AP1 GO:0098588 bounding membrane of organelle ARBA:ARBA00027281 KEEP_AS_NON_CORE very general (>200 descendants) 201 human/ATP6AP2 GO:0005737 cytoplasm ARBA:ARBA00026971 KEEP_AS_NON_CORE very general (>200 descendants) 1146 human/ATP6AP2 GO:0098588 bounding membrane of organelle ARBA:ARBA00027281 KEEP_AS_NON_CORE very general (>200 descendants) 201 human/ATP6V0C GO:0098588 bounding membrane of organelle ARBA:ARBA00027281 ACCEPT very general (>200 descendants) 201 human/ATP6V0D1 GO:0016471 vacuolar proton-transporting V-type ATPase complex ARBA:ARBA00088504 ACCEPT specific (1-20) 5 human/ATP6V0D1 GO:0030670 phagocytic vesicle membrane ARBA:ARBA00026470 KEEP_AS_NON_CORE specific (1-20) 3 human/ATP6V0D1 GO:0042592 homeostatic process ARBA:ARBA00027526 MARK_AS_OVER_ANNOTATED very general (>200 descendants) 255 TOO_GENERAL true but uninformative generic The specific supported homeostatic roles are endolysosomal acidification, proton transmembrane transport, and context-specific iron/HIF regulation. The generic parent term loses the actual function. human/ATP6V0D2 GO:0016471 vacuolar proton-transporting V-type ATPase complex ARBA:ARBA00088504 ACCEPT specific (1-20) 5 human/ATP6V0D2 GO:0030670 phagocytic vesicle membrane ARBA:ARBA00026470 KEEP_AS_NON_CORE specific (1-20) 3 human/ATP6V1A GO:0042592 homeostatic process ARBA:ARBA00027526 MARK_AS_OVER_ANNOTATED very general (>200 descendants) 255 TOO_GENERAL true but uninformative general This ARBA annotation is too general. The specific homeostatic processes (lysosomal acidification, pH regulation) are better captured by more precise GO terms already annotated. human/ATP6V1B1 GO:0000221 vacuolar proton-transporting V-type ATPase, V1 domain ARBA:ARBA00090169 ACCEPT specific (1-20) 1 human/ATP6V1C1 GO:0016020 membrane ARBA:ARBA00028763 MARK_AS_OVER_ANNOTATED very general (>200 descendants) 895 TOO_GENERAL true but uninformative broad Too broad; the specific membrane compartment annotations (lysosomal membrane, synaptic vesicle membrane) are more informative. IEA evidence from automated annotation. human/ATP6V1G1 GO:0051117 ATPase binding ARBA:ARBA00087746 ACCEPT leaf (0) 0 human/ATP6V1G3 GO:0051117 ATPase binding ARBA:ARBA00087746 ACCEPT leaf (0) 0 human/ATP6V1H GO:0016020 membrane ARBA:ARBA00028763 MODIFY very general (>200 descendants) 895 NEEDS_MORE_SPECIFIC true but uninformative replacement term Generic membrane is too imprecise. The more specific terms lysosomal membrane (HDA), endosome membrane (NAS), and plasma membrane (NAS) already exist in the annotation set. The IDA annotation to GO:0016020 from PMID:33065002 directly contextualizes which membrane is meant. human/ATP7A GO:0005768 endosome ARBA:ARBA00028568 KEEP_AS_NON_CORE general (21-200) 68 human/ATP7B GO:0005375 copper ion transmembrane transporter activity ARBA:ARBA00028756 MODIFY specific (1-20) 5 NEEDS_MORE_SPECIFIC true but uninformative replacement term The ARBA-derived copper transmembrane transporter assertion is sound but general. Refine it to the established ATP-driven P-type Cu(I) mechanism, independently corroborated by human ATP7B expressed in Sf9 microsomal vesicles in PMID:22240481. This is a specificity correction of the existing assertion; it does not add a new activity or treat the ancestor as biologically false. human/ATP7B GO:0046688 response to copper ion ARBA:ARBA00092178 ACCEPT specific (1-20) 4 human/ATP7B GO:0032588 trans-Golgi network membrane ARBA:ARBA00033972 ACCEPT specific (1-20) 2 human/ATP8A2 GO:0012505 endomembrane system ARBA:ARBA00028953 MODIFY very general (>200 descendants) 357 NEEDS_MORE_SPECIFIC true but uninformative replacement term ARBA00028953 supplies a broad endomembrane assignment. Independent localization and integral-membrane architecture support Golgi membrane and endosome membrane as the informative reviewed locations. human/ATP8A2 GO:1990531 phospholipid-translocating ATPase complex ARBA:ARBA00090460 ACCEPT specific (1-20) 1 human/ATRX GO:0010564 regulation of cell cycle process ARBA:ARBA00027431 KEEP_AS_NON_CORE very general (>200 descendants) 338 human/ATRX GO:0016604 nuclear body ARBA:ARBA00043611 ACCEPT specific (1-20) 16 human/ATRX GO:0033044 regulation of chromosome organization ARBA:ARBA00029256 KEEP_AS_NON_CORE general (21-200) 140 human/ATRX GO:0045944 positive regulation of transcription by RNA polymerase II ARBA:ARBA00027996 KEEP_AS_NON_CORE specific (1-20) 12 human/ATXN10 GO:0120025 plasma membrane bounded cell projection ARBA:ARBA00028036 KEEP_AS_NON_CORE very general (>200 descendants) 303 human/ATXN10 GO:0120036 plasma membrane bounded cell projection organization ARBA:ARBA00028051 KEEP_AS_NON_CORE general (21-200) 196 human/AUH GO:0003723 RNA binding ARBA:ARBA00028406 ACCEPT general (21-200) 163 human/AUH GO:0004300 enoyl-CoA hydratase activity ARBA:ARBA00086629 KEEP_AS_NON_CORE specific (1-20) 5 human/AUH GO:0009083 branched-chain amino acid catabolic process ARBA:ARBA00091432 MODIFY specific (1-20) 4 NEEDS_MORE_SPECIFIC true but uninformative replacement term AUH directly catalyzes a leucine-catabolic step. The broader branched-chain amino-acid label can be refined to the substrate pathway established for this enzyme, without implying equivalent valine or isoleucine roles. human/AUH GO:0170035 obsolete L-amino acid catabolic process ARBA:ARBA00044574 MODIFY leaf (0) 0 OTHER_TERM different term needed replacement term The official AmiGO record confirms that this source term was obsoleted as an unnecessary grouping term. Its underlying amino-acid-catabolic meaning is consistent with AUH biology. Preserve the original identifier and refine the review to the directly established leucine-catabolic process. human/AURKA GO:0004712 protein serine/threonine/tyrosine kinase activity ARBA:ARBA00043550 MODIFY specific (1-20) 2 OTHER_TERM different term needed replacement term "[file:human/AURKA/AURKA-uniprot.txt ""CC Reaction=L-seryl-[protein] + ATP = O-phospho-L-seryl-[protein] + ADP +""] [file:human/AURKA/AURKA-uniprot.txt ""CC Reaction=L-threonyl-[protein] + ATP = O-phospho-L-threonyl-[protein] +""] [file:human/AURKA/AURKA-uniprot.txt ""CC -!- FUNCTION: Mitotic serine/threonine kinase that contributes to the""]" human/AURKA GO:0007051 spindle organization ARBA:ARBA00043498 ACCEPT general (21-200) 36 human/AURKA GO:0030496 midbody ARBA:ARBA00033509 KEEP_AS_NON_CORE specific (1-20) 1 human/AURKA GO:0090068 positive regulation of cell cycle process ARBA:ARBA00029176 ACCEPT general (21-200) 104 human/AURKB GO:0004712 protein serine/threonine/tyrosine kinase activity ARBA:ARBA00043550 MODIFY specific (1-20) 2 OTHER_TERM different term needed replacement term "[file:human/AURKB/AURKB-uniprot.txt ""CC Reaction=L-seryl-[protein] + ATP = O-phospho-L-seryl-[protein] + ADP +""] [file:human/AURKB/AURKB-uniprot.txt ""CC Reaction=L-threonyl-[protein] + ATP = O-phospho-L-threonyl-[protein] +""]" human/AURKB GO:0007051 spindle organization ARBA:ARBA00043498 ACCEPT general (21-200) 36 human/AURKB GO:0090068 positive regulation of cell cycle process ARBA:ARBA00029176 ACCEPT general (21-200) 104 human/AURKC GO:0004712 protein serine/threonine/tyrosine kinase activity ARBA:ARBA00043550 MODIFY specific (1-20) 2 OTHER_TERM different term needed replacement term The official GO:0004712 definition requires serine, threonine and tyrosine phosphorylation. The independently inspected human Aurora-C experiments establish serine/threonine catalysis, providing GO:0004674 as a supported replacement. This is a specificity correction, not a claim that an exhaustive search disproved every possible tyrosine substrate or that the current term is a synonym for serine/threonine kinase. human/AURKC GO:0007051 spindle organization ARBA:ARBA00043498 UNDECIDED general (21-200) 36 human/AURKC GO:0030496 midbody ARBA:ARBA00033509 ACCEPT specific (1-20) 1 human/AURKC GO:0090068 positive regulation of cell cycle process ARBA:ARBA00029176 ACCEPT general (21-200) 104 human/AXIN1 GO:0030178 negative regulation of Wnt signaling pathway ARBA:ARBA00027587 ACCEPT specific (1-20) 7 human/AXIN2 GO:0031625 ubiquitin protein ligase binding ARBA:ARBA00028807 KEEP_AS_NON_CORE leaf (0) 0 human/AZIN2 GO:0016831 carboxy-lyase activity ARBA:ARBA00026976 REMOVE general (21-200) 99 NONCATALYTIC_HOMOLOG wrong manual NONCATALYTIC_HOMOLOG Electronic over-propagation of decarboxylase activity onto AZIN2, which lacks it (curated NOT|ODC). Remove. human/B3GALNT1 GO:1901135 carbohydrate derivative metabolic process ARBA:ARBA00026297 KEEP_AS_NON_CORE very general (>200 descendants) 637 human/B3GALT6 GO:0006024 glycosaminoglycan biosynthetic process ARBA:ARBA00027325 ACCEPT specific (1-20) 3 human/B3GNT5 GO:0030148 sphingolipid biosynthetic process ARBA:ARBA00027455 KEEP_AS_NON_CORE specific (1-20) 18 human/B3GNT5 GO:1901135 carbohydrate derivative metabolic process ARBA:ARBA00026297 KEEP_AS_NON_CORE very general (>200 descendants) 637 human/B4GALNT1 GO:0008376 acetylgalactosaminyltransferase activity ARBA:ARBA00026814 MODIFY specific (1-20) 10 NEEDS_MORE_SPECIFIC true but uninformative replacement term Refine this gene-level ARBA assertion to GO:0003947 using the established B4GALNT1 GM3/GD3 transfer reaction. This differs from the IBA row, which records the broader function inherited from a PAINT ancestral node; no revised ancestral substrate specificity is inferred. The specific replacement is already represented by independent evidence rows and adds no new assertion. human/B4GALNT1 GO:1901135 carbohydrate derivative metabolic process ARBA:ARBA00026297 MODIFY very general (>200 descendants) 637 NEEDS_MORE_SPECIFIC true but uninformative replacement term B4GALNT1 itself transfers GalNAc to ganglioside precursors. GO:0001574 specifies this direct contribution more precisely than the broad ARBA metabolic term and is already present. human/B4GALT1 GO:0000139 Golgi membrane ARBA:ARBA00029253 ACCEPT specific (1-20) 6 human/B4GALT5 GO:0000139 Golgi membrane ARBA:ARBA00029253 ACCEPT specific (1-20) 6 human/B4GALT5 GO:1901137 carbohydrate derivative biosynthetic process ARBA:ARBA00026302 MARK_AS_OVER_ANNOTATED very general (>200 descendants) 296 TOO_GENERAL true but uninformative general Over-general parent; specific glycosphingolipid/LacCer biosynthesis terms capture the biology. human/B4GALT6 GO:0000139 Golgi membrane ARBA:ARBA00029253 ACCEPT specific (1-20) 6 human/B4GALT6 GO:1901137 carbohydrate derivative biosynthetic process ARBA:ARBA00026302 KEEP_AS_NON_CORE very general (>200 descendants) 296 human/B4GALT7 GO:0000139 Golgi membrane ARBA:ARBA00029253 ACCEPT specific (1-20) 6 human/B9D1 GO:0005929 cilium ARBA:ARBA00028353 MODIFY general (21-200) 115 NEEDS_MORE_SPECIFIC true but uninformative replacement term Tagged human B9D1 localizes to the transition zone in RPE1 cells (PMID:32726168), consistent with the transition-zone complex described in PMID:22179047. This anatomical compartment is part of the cilium and provides a more precise location for the electronic annotation. The destination is already represented by other transition-zone annotations; this refines the existing broad source row rather than adding a new location assertion. human/B9D2 GO:0005929 cilium ARBA:ARBA00028353 ACCEPT general (21-200) 115 human/BAAT GO:0006629 lipid metabolic process ARBA:ARBA00028591 KEEP_AS_NON_CORE very general (>200 descendants) 608 human/BAAT GO:0032787 monocarboxylic acid metabolic process ARBA:ARBA00027288 KEEP_AS_NON_CORE very general (>200 descendants) 286 human/BAAT GO:0047617 fatty acyl-CoA hydrolase activity ARBA:ARBA00028962 KEEP_AS_NON_CORE specific (1-20) 5 human/BACE2 GO:0006509 membrane protein ectodomain proteolysis ARBA:ARBA00085430 ACCEPT specific (1-20) 1 human/BAG1 GO:0043066 negative regulation of apoptotic process ARBA:ARBA00027746 MARK_AS_OVER_ANNOTATED general (21-200) 79 INDIRECT_EFFECT overreach indirect "Over-annotation. BAG1's primary function is proteostasis via Hsp70 co-chaperoning. Anti-apoptotic effects are indirect and secondary to chaperoning function. The name ""BCL2-associated athanogene"" is historical but misleading about the core molecular function [deep research, PMID:9305631]." human/BAG2 GO:0006457 protein folding ARBA:ARBA00027200 ACCEPT specific (1-20) 7 human/BAG2 GO:0051247 positive regulation of protein metabolic process ARBA:ARBA00028881 MARK_AS_OVER_ANNOTATED general (21-200) 138 TOO_GENERAL true but uninformative general positive regulation of protein metabolic process is too general to convey BAG2 function and duplicates more specific accepted terms. human/BAG3 GO:0006457 protein folding ARBA:ARBA00027200 ACCEPT specific (1-20) 7 human/BAG3 GO:0010664 negative regulation of striated muscle cell apoptotic process ARBA:ARBA00092005 KEEP_AS_NON_CORE specific (1-20) 1 human/BAG3 GO:0050821 protein stabilization ARBA:ARBA00033884 ACCEPT leaf (0) 0 human/BAG3 GO:0097191 extrinsic apoptotic signaling pathway ARBA:ARBA00028297 KEEP_AS_NON_CORE specific (1-20) 8 human/BAIAP2 GO:0070064 proline-rich region binding ARBA:ARBA00027804 ACCEPT leaf (0) 0 human/BAIAP2 GO:0005886 plasma membrane ARBA:ARBA00027801 ACCEPT very general (>200 descendants) 415 human/BAIAP2L1 GO:0070064 proline-rich region binding ARBA:ARBA00027804 ACCEPT leaf (0) 0 human/BAK1 GO:0032469 endoplasmic reticulum calcium ion homeostasis ARBA:ARBA00084258 KEEP_AS_NON_CORE specific (1-20) 5 human/BAK1 GO:0043065 positive regulation of apoptotic process ARBA:ARBA00027745 MODIFY general (21-200) 68 OTHER_TERM different term needed replacement term BAK is a positive intrinsic-apoptosis effector because it permeabilizes the mitochondrial outer membrane; broad positive regulation of apoptosis hides the direct step. human/BAK1 GO:0051049 regulation of transport ARBA:ARBA00027251 REMOVE very general (>200 descendants) 960 INDIRECT overreach manual INDIRECT The annotation is a stress, development, transport, or signaling-level projection from ortholog or ARBA/Ensembl data and is too far from BAK's direct MOMP effector activity to retain for human BAK1. human/BAK1 GO:0051246 regulation of protein metabolic process ARBA:ARBA00028884 REMOVE very general (>200 descendants) 442 INDIRECT overreach manual INDIRECT The annotation is a stress, development, transport, or signaling-level projection from ortholog or ARBA/Ensembl data and is too far from BAK's direct MOMP effector activity to retain for human BAK1. human/BAK1 GO:0070059 intrinsic apoptotic signaling pathway in response to endoplasmic reticulum stress ARBA:ARBA00092512 KEEP_AS_NON_CORE specific (1-20) 1 human/BAK1 GO:1902531 regulation of intracellular signal transduction ARBA:ARBA00027126 REMOVE very general (>200 descendants) 278 INDIRECT overreach manual INDIRECT The annotation is a stress, development, transport, or signaling-level projection from ortholog or ARBA/Ensembl data and is too far from BAK's direct MOMP effector activity to retain for human BAK1. human/BAK1 GO:2001233 regulation of apoptotic signaling pathway ARBA:ARBA00027033 MODIFY general (21-200) 57 OTHER_TERM different term needed replacement term The ARBA row captures the correct apoptosis branch only generically; BAK directly permeabilizes the mitochondrial outer membrane. human/BAP1 GO:0003682 chromatin binding ARBA:ARBA00027831 ACCEPT specific (1-20) 10 human/BAP1 GO:0010468 regulation of gene expression ARBA:ARBA00028334 MODIFY very general (>200 descendants) 874 NEEDS_MORE_SPECIFIC true but uninformative replacement term Human chromatin and transcription experiments support GO:0006355, a verified child of regulation of gene expression. This refinement preserves both activating and repressive contexts without asserting universal directionality. human/BAX GO:0001836 release of cytochrome c from mitochondria ARBA:ARBA00091670 ACCEPT leaf (0) 0 human/BAX GO:0033554 cellular response to stress ARBA:ARBA00028184 REMOVE very general (>200 descendants) 285 INDIRECT overreach manual INDIRECT Many stresses can signal upstream to BAX, but that does not make BAX a direct executor of a generic cellular response to stress. human/BAX GO:0043065 positive regulation of apoptotic process ARBA:ARBA00027745 MODIFY general (21-200) 68 OTHER_TERM different term needed replacement term BAX is one of the pore-forming effectors that permeabilizes the mitochondrial outer membrane rather than a generic regulator of apoptotic process. human/BAX GO:0043523 regulation of neuron apoptotic process ARBA:ARBA00085497 MARK_AS_OVER_ANNOTATED specific (1-20) 18 TOO_GENERAL true but uninformative generic BAX can promote neuronal apoptosis through its usual mitochondrial effector function, but a generic ARBA transfer to regulation of neuron apoptotic process overstates this as a separate function. human/BAX GO:0097136 Bcl-2 family protein complex ARBA:ARBA00034603 ACCEPT specific (1-20) 12 human/BAX GO:1902531 regulation of intracellular signal transduction ARBA:ARBA00027126 REMOVE very general (>200 descendants) 278 INDIRECT overreach manual INDIRECT BAX has a defined mitochondrial effector role and should not inherit a generic regulation of intracellular signal transduction term from ARBA. human/BAX GO:2001233 regulation of apoptotic signaling pathway ARBA:ARBA00027033 MODIFY general (21-200) 57 OTHER_TERM different term needed replacement term BAX directly permeabilizes the mitochondrial outer membrane rather than merely regulating apoptotic signaling generically. human/BAZ2A GO:0005654 nucleoplasm ARBA:ARBA00026290 ACCEPT general (21-200) 65 human/BBS1 GO:0001895 retina homeostasis ARBA:ARBA00091684 KEEP_AS_NON_CORE specific (1-20) 3 human/BBS1 GO:0008104 intracellular protein localization ARBA:ARBA00028253 MODIFY very general (>200 descendants) 356 NEEDS_MORE_SPECIFIC true but uninformative replacement term BBS1 participates in BBSome-dependent delivery of cargo to cilia. BBS1 depletion or mutation impairs polycystin-1 ciliary targeting without disrupting its general plasma-membrane delivery, supporting refinement of intracellular localization to the ciliary process. human/BBS4 GO:0000226 microtubule cytoskeleton organization ARBA:ARBA00028425 KEEP_AS_NON_CORE general (21-200) 119 human/BBS4 GO:0007600 sensory perception ARBA:ARBA00027936 KEEP_AS_NON_CORE general (21-200) 81 human/BBS4 GO:0035869 ciliary transition zone ARBA:ARBA00092392 ACCEPT specific (1-20) 8 human/BBS4 GO:0061512 protein localization to cilium ARBA:ARBA00091714 ACCEPT specific (1-20) 8 human/BBS4 GO:0097730 non-motile cilium ARBA:ARBA00026428 ACCEPT specific (1-20) 18 human/BCAT2 GO:0009082 branched-chain amino acid biosynthetic process ARBA:ARBA00028438 KEEP_AS_NON_CORE specific (1-20) 3 human/BCAT2 GO:0009083 branched-chain amino acid catabolic process ARBA:ARBA00091432 ACCEPT specific (1-20) 4 human/BCL11A GO:0005654 nucleoplasm ARBA:ARBA00026290 ACCEPT general (21-200) 65 human/BCL11A GO:0006357 regulation of transcription by RNA polymerase II ARBA:ARBA00028137 ACCEPT general (21-200) 56 human/BCL11A GO:0016514 SWI/SNF complex ARBA:ARBA00027834 ACCEPT leaf (0) 0 human/BCL11B GO:0005654 nucleoplasm ARBA:ARBA00026290 ACCEPT general (21-200) 65 human/BCL11B GO:0006357 regulation of transcription by RNA polymerase II ARBA:ARBA00028137 ACCEPT general (21-200) 56 human/BCL2 GO:0097136 Bcl-2 family protein complex ARBA:ARBA00034603 ACCEPT specific (1-20) 12 human/BCL2 GO:1902531 regulation of intracellular signal transduction ARBA:ARBA00027126 ACCEPT very general (>200 descendants) 278 human/BCL2 GO:2001233 regulation of apoptotic signaling pathway ARBA:ARBA00027033 ACCEPT general (21-200) 57 human/BCL2L1 GO:0006950 response to stress ARBA:ARBA00026300 MARK_AS_OVER_ANNOTATED very general (>200 descendants) 590 TOO_GENERAL true but uninformative broad This term is extremely broad. While Bcl-xL is regulated by and responds to various stresses, this high-level term does not capture the specific molecular function. More specific terms like those for apoptotic signaling pathways are preferred. human/BCL2L1 GO:0043066 negative regulation of apoptotic process ARBA:ARBA00027746 ACCEPT general (21-200) 79 human/BCL2L1 GO:0051707 response to other organism ARBA:ARBA00029118 MARK_AS_OVER_ANNOTATED general (21-200) 199 INDIRECT_EFFECT overreach indirect "This annotation is too indirect. Bcl-xL is targeted by pathogens (e.g., SARS-CoV 7a) but does not itself ""respond"" to organisms. The annotation conflates being a target with being a response mechanism." human/BCL2L1 GO:0097136 Bcl-2 family protein complex ARBA:ARBA00034603 ACCEPT specific (1-20) 12 human/BCL2L1 GO:1902531 regulation of intracellular signal transduction ARBA:ARBA00027126 MARK_AS_OVER_ANNOTATED very general (>200 descendants) 278 TOO_GENERAL true but uninformative broad This term is too broad and non-specific. More precise annotations about apoptotic signaling pathway regulation are already present and provide better information about the actual function. human/BCL2L1 GO:2001233 regulation of apoptotic signaling pathway ARBA:ARBA00027033 ACCEPT general (21-200) 57 human/BCS1L GO:0034551 mitochondrial respiratory chain complex III assembly ARBA:ARBA00092360 ACCEPT leaf (0) 0 human/BDH1 GO:0016616 oxidoreductase activity, acting on the CH-OH group of donors, NAD or NADP as acceptor ARBA:ARBA00028442 MARK_AS_OVER_ANNOTATED very general (>200 descendants) 364 TOO_GENERAL true but uninformative redundant Not incorrect, but redundant with and far less informative than the specific EC 1.1.1.30 activity (GO:0003858) already annotated by IBA/IDA/RHEA. The specific term should be used to represent the molecular function. human/BECN1 GO:0032801 receptor catabolic process ARBA:ARBA00085467 ACCEPT specific (1-20) 3 human/BECN2 GO:0032801 receptor catabolic process ARBA:ARBA00085467 ACCEPT specific (1-20) 3 human/BEST1 GO:0015267 channel activity ARBA:ARBA00028041 MODIFY general (21-200) 171 NEEDS_MORE_SPECIFIC true but uninformative replacement term ARBA channel activity is compatible with BEST1 biology but loses the substrate and gating information established experimentally. The two existing specific activities describe the same oligomeric pore; no extra channel or new annotation row is proposed. human/BID GO:0033554 cellular response to stress ARBA:ARBA00028184 MARK_AS_OVER_ANNOTATED very general (>200 descendants) 285 TOO_GENERAL true but uninformative broad The imported ancestor-level term is not entirely false, but it is much broader than BID's direct apoptotic MOMP-regulator role and should not be kept as a curated BID process. human/BID GO:0035556 intracellular signal transduction ARBA:ARBA00026887 MARK_AS_OVER_ANNOTATED general (21-200) 195 TOO_GENERAL true but uninformative broad The imported ancestor-level term is not entirely false, but it is much broader than BID's direct apoptotic MOMP-regulator role and should not be kept as a curated BID process. human/BID GO:1902531 regulation of intracellular signal transduction ARBA:ARBA00027126 MARK_AS_OVER_ANNOTATED very general (>200 descendants) 278 TOO_GENERAL true but uninformative broad The imported ancestor-level term is not entirely false, but it is much broader than BID's direct apoptotic MOMP-regulator role and should not be kept as a curated BID process. human/BID GO:2001233 regulation of apoptotic signaling pathway ARBA:ARBA00027033 MODIFY general (21-200) 57 OTHER_TERM different term needed replacement term BID acts at the BCL2-family branch point that amplifies intrinsic mitochondrial apoptotic signaling; the signed descendant captures the supported direction. human/BIN1 GO:0006897 endocytosis ARBA:ARBA00027119 ACCEPT general (21-200) 64 human/BIN1 GO:0016020 membrane ARBA:ARBA00028763 ACCEPT very general (>200 descendants) 895 human/BIN1 GO:0030424 axon ARBA:ARBA00028032 ACCEPT general (21-200) 59 human/BIN1 GO:0051649 establishment of localization in cell ARBA:ARBA00028679 MODIFY very general (>200 descendants) 411 OTHER_TERM different term needed replacement term Establishment of localization in cell is broad but biologically compatible with BIN1. Breadth alone is not over-annotation. Endocytosis is a supported, more informative process in the available evidence and already represented elsewhere in GOA; this replacement adds no independent evidence or new process assertion. ARBA rule placement itself was not audited. human/BIRC5 GO:0043066 negative regulation of apoptotic process ARBA:ARBA00027746 KEEP_AS_NON_CORE general (21-200) 79 human/BIRC6 GO:0016567 protein ubiquitination ARBA:ARBA00027966 ACCEPT specific (1-20) 14 human/BIRC6 GO:0042127 regulation of cell population proliferation ARBA:ARBA00027546 KEEP_AS_NON_CORE very general (>200 descendants) 258 human/BIRC6 GO:0043066 negative regulation of apoptotic process ARBA:ARBA00027746 ACCEPT general (21-200) 79 human/BLM GO:0000723 telomere maintenance ARBA:ARBA00027335 ACCEPT specific (1-20) 18 human/BLM GO:0000724 double-strand break repair via homologous recombination ARBA:ARBA00027336 ACCEPT specific (1-20) 14 human/BLM GO:0031297 replication fork processing ARBA:ARBA00086530 ACCEPT specific (1-20) 4 human/BLM GO:0032392 DNA geometric change ARBA:ARBA00027691 ACCEPT leaf (0) 0 human/BLM GO:0045910 negative regulation of DNA recombination ARBA:ARBA00086129 ACCEPT specific (1-20) 15 human/BLOC1S6 GO:0031410 cytoplasmic vesicle ARBA:ARBA00027190 KEEP_AS_NON_CORE very general (>200 descendants) 274 human/BLVRB GO:0030219 megakaryocyte differentiation ARBA:ARBA00085624 KEEP_AS_NON_CORE specific (1-20) 1 human/BMP10 GO:0010611 regulation of cardiac muscle hypertrophy ARBA:ARBA00091898 KEEP_AS_NON_CORE specific (1-20) 7 human/BMP10 GO:0051240 positive regulation of multicellular organismal process ARBA:ARBA00028891 MODIFY very general (>200 descendants) 565 NEEDS_MORE_SPECIFIC true but uninformative replacement term The near-root ARBA term does not identify which organismal response BMP10 regulates. PMID:17921333 provides independent support for a cardiac hypertrophic response to BMP10-containing conditioned medium in neonatal rat cardiomyocytes. Refine to GO:0010613, already present among the reviewed assertions, without claiming reconstruction of the ARBA training provenance. This contextual effect is not a universal BMP10 response: PMID:16798733 reports reduced postnatal cardiomyocyte enlargement under myocardial overexpression. The refinement preserves a supported specific outcome rather than treating broadness as biological falsity. human/BMP10 GO:0090092 regulation of transmembrane receptor protein serine/threonine kinase signaling pathway ARBA:ARBA00027948 ACCEPT specific (1-20) 20 human/BMP4 GO:0001649 osteoblast differentiation ARBA:ARBA00089865 KEEP_AS_NON_CORE specific (1-20) 2 human/BMP4 GO:0002573 myeloid leukocyte differentiation ARBA:ARBA00088984 UNDECIDED specific (1-20) 20 human/BMP4 GO:0003007 heart morphogenesis ARBA:ARBA00086699 KEEP_AS_NON_CORE general (21-200) 98 human/BMP4 GO:0003129 heart induction ARBA:ARBA00088459 UNDECIDED leaf (0) 0 human/BMP4 GO:0005125 cytokine activity ARBA:ARBA00027187 ACCEPT specific (1-20) 1 human/BMP4 GO:0021537 telencephalon development ARBA:ARBA00084940 KEEP_AS_NON_CORE general (21-200) 80 human/BMP4 GO:0022408 negative regulation of cell-cell adhesion ARBA:ARBA00092663 UNDECIDED general (21-200) 66 human/BMP4 GO:0030501 positive regulation of bone mineralization ARBA:ARBA00086906 KEEP_AS_NON_CORE specific (1-20) 1 human/BMP4 GO:0030858 positive regulation of epithelial cell differentiation ARBA:ARBA00088239 KEEP_AS_NON_CORE specific (1-20) 18 human/BMP4 GO:0039706 co-receptor binding ARBA:ARBA00089206 KEEP_AS_NON_CORE leaf (0) 0 human/BMP4 GO:0043065 positive regulation of apoptotic process ARBA:ARBA00027745 KEEP_AS_NON_CORE general (21-200) 68 human/BMP4 GO:0045893 positive regulation of DNA-templated transcription ARBA:ARBA00029082 KEEP_AS_NON_CORE general (21-200) 42 human/BMP4 GO:0048662 negative regulation of smooth muscle cell proliferation ARBA:ARBA00091356 KEEP_AS_NON_CORE specific (1-20) 1 human/BMP4 GO:0051241 negative regulation of multicellular organismal process ARBA:ARBA00033877 UNDECIDED very general (>200 descendants) 560 human/BMP4 GO:0060391 positive regulation of SMAD protein signal transduction ARBA:ARBA00090778 ACCEPT leaf (0) 0 human/BMP4 GO:0060426 lung vasculature development ARBA:ARBA00090964 KEEP_AS_NON_CORE leaf (0) 0 human/BMP4 GO:0060441 epithelial tube branching involved in lung morphogenesis ARBA:ARBA00091049 KEEP_AS_NON_CORE specific (1-20) 9 human/BMP4 GO:0060537 muscle tissue development ARBA:ARBA00090616 KEEP_AS_NON_CORE general (21-200) 80 human/BMP4 GO:0061036 positive regulation of cartilage development ARBA:ARBA00090328 UNDECIDED specific (1-20) 3 human/BMP4 GO:0070700 BMP receptor binding ARBA:ARBA00084348 ACCEPT leaf (0) 0 human/BMP4 GO:0071773 cellular response to BMP stimulus ARBA:ARBA00085410 KEEP_AS_NON_CORE specific (1-20) 2 human/BMP4 GO:0090189 regulation of branching involved in ureteric bud morphogenesis ARBA:ARBA00087293 KEEP_AS_NON_CORE specific (1-20) 2 human/BMP4 GO:1900745 positive regulation of p38MAPK cascade ARBA:ARBA00085720 KEEP_AS_NON_CORE leaf (0) 0 human/BMP4 GO:2000725 regulation of cardiac muscle cell differentiation ARBA:ARBA00085921 KEEP_AS_NON_CORE specific (1-20) 6 human/BMP6 GO:0009888 tissue development ARBA:ARBA00028065 KEEP_AS_NON_CORE very general (>200 descendants) 1023 human/BMP6 GO:0030509 BMP signaling pathway ARBA:ARBA00086900 ACCEPT specific (1-20) 1 human/BMP6 GO:0042127 regulation of cell population proliferation ARBA:ARBA00027546 KEEP_AS_NON_CORE very general (>200 descendants) 258 human/BMP6 GO:0045597 positive regulation of cell differentiation ARBA:ARBA00028476 KEEP_AS_NON_CORE very general (>200 descendants) 224 human/BMP6 GO:0048468 cell development ARBA:ARBA00028665 KEEP_AS_NON_CORE very general (>200 descendants) 672 human/BMP6 GO:0070700 BMP receptor binding ARBA:ARBA00084348 ACCEPT leaf (0) 0 human/BMP6 GO:2000026 regulation of multicellular organismal development ARBA:ARBA00026275 KEEP_AS_NON_CORE very general (>200 descendants) 464 human/BMPR1A GO:0030501 positive regulation of bone mineralization ARBA:ARBA00086906 KEEP_AS_NON_CORE specific (1-20) 1 human/BMPR1A GO:0045669 positive regulation of osteoblast differentiation ARBA:ARBA00084608 KEEP_AS_NON_CORE leaf (0) 0 human/BMPR1A GO:0045944 positive regulation of transcription by RNA polymerase II ARBA:ARBA00027996 KEEP_AS_NON_CORE specific (1-20) 12 human/BMPR1A GO:0046332 SMAD binding ARBA:ARBA00034981 ACCEPT specific (1-20) 3 human/BMPR1A GO:1990712 HFE-transferrin receptor complex ARBA:ARBA00088952 UNDECIDED leaf (0) 0 human/BMPR2 GO:0001558 regulation of cell growth ARBA:ARBA00090177 KEEP_AS_NON_CORE general (21-200) 66 human/BMPR2 GO:0001944 vasculature development ARBA:ARBA00091285 KEEP_AS_NON_CORE general (21-200) 132 human/BMPR2 GO:0009888 tissue development ARBA:ARBA00028065 KEEP_AS_NON_CORE very general (>200 descendants) 1023 human/BMPR2 GO:0030054 cell junction ARBA:ARBA00028333 KEEP_AS_NON_CORE general (21-200) 189 human/BMPR2 GO:0030324 lung development ARBA:ARBA00087373 KEEP_AS_NON_CORE general (21-200) 50 human/BMPR2 GO:0040017 positive regulation of locomotion ARBA:ARBA00026460 KEEP_AS_NON_CORE general (21-200) 88 human/BMPR2 GO:0045597 positive regulation of cell differentiation ARBA:ARBA00028476 KEEP_AS_NON_CORE very general (>200 descendants) 224 human/BMPR2 GO:2000026 regulation of multicellular organismal development ARBA:ARBA00026275 KEEP_AS_NON_CORE very general (>200 descendants) 464 human/BPTF GO:0006338 chromatin remodeling ARBA:ARBA00027994 ACCEPT very general (>200 descendants) 235 human/BPTF GO:0045892 negative regulation of DNA-templated transcription ARBA:ARBA00029084 KEEP_AS_NON_CORE general (21-200) 39 human/BPTF GO:0045944 positive regulation of transcription by RNA polymerase II ARBA:ARBA00027996 ACCEPT specific (1-20) 12 human/BRAF GO:0043066 negative regulation of apoptotic process ARBA:ARBA00027746 ACCEPT general (21-200) 79 human/BRCA1 GO:0005654 nucleoplasm ARBA:ARBA00026290 ACCEPT general (21-200) 65 human/BRD4 GO:0006355 regulation of DNA-templated transcription ARBA:ARBA00028138 ACCEPT general (21-200) 140 human/BRIP1 GO:0006281 DNA repair ARBA:ARBA00029008 ACCEPT general (21-200) 74 human/BRPF1 GO:0070776 MOZ/MORF histone acetyltransferase complex ARBA:ARBA00084417 ACCEPT leaf (0) 0 human/BRSK2 GO:0000086 G2/M transition of mitotic cell cycle ARBA:ARBA00090227 KEEP_AS_NON_CORE leaf (0) 0 human/BRSK2 GO:2000807 regulation of synaptic vesicle clustering ARBA:ARBA00085644 UNDECIDED specific (1-20) 2 human/BTK GO:0005829 cytosol ARBA:ARBA00029243 ACCEPT general (21-200) 73 human/BTK GO:0042113 B cell activation ARBA:ARBA00085935 ACCEPT general (21-200) 44 human/BTK GO:0050864 regulation of B cell activation ARBA:ARBA00091725 ACCEPT general (21-200) 38 human/BUB1B GO:0033045 regulation of sister chromatid segregation ARBA:ARBA00029259 ACCEPT general (21-200) 53 human/BUB3 GO:0000776 kinetochore ARBA:ARBA00027576 ACCEPT specific (1-20) 11 human/C1GALT1C1 GO:0006493 protein O-linked glycosylation ARBA:ARBA00027289 ACCEPT specific (1-20) 17 human/C2CD3 GO:0060271 cilium assembly ARBA:ARBA00027837 ACCEPT specific (1-20) 19 human/C2CD3 GO:0071539 protein localization to centrosome ARBA:ARBA00092420 ACCEPT specific (1-20) 2 human/C3 GO:0051707 response to other organism ARBA:ARBA00029118 KEEP_AS_NON_CORE general (21-200) 199 human/C3 GO:2000427 positive regulation of apoptotic cell clearance ARBA:ARBA00086842 KEEP_AS_NON_CORE specific (1-20) 1 human/CACNA1C GO:0005737 cytoplasm ARBA:ARBA00026971 KEEP_AS_NON_CORE very general (>200 descendants) 1146 human/CACNA1C GO:0006936 muscle contraction ARBA:ARBA00043367 ACCEPT general (21-200) 53 human/CACNA1C GO:0008331 high voltage-gated calcium channel activity ARBA:ARBA00091987 ACCEPT leaf (0) 0 human/CACNA1C GO:0014069 postsynaptic density ARBA:ARBA00027264 ACCEPT specific (1-20) 4 human/CACNA1C GO:0042391 regulation of membrane potential ARBA:ARBA00028934 ACCEPT general (21-200) 154 human/CACNA1C GO:0048513 animal organ development ARBA:ARBA00029247 KEEP_AS_NON_CORE very general (>200 descendants) 1888 human/CACNA1C GO:0048731 system development ARBA:ARBA00027702 KEEP_AS_NON_CORE very general (>200 descendants) 2438 human/CACNA1C GO:0061577 calcium ion transmembrane transport via high voltage-gated calcium channel ARBA:ARBA00098387 ACCEPT leaf (0) 0 human/CACNA1C GO:1990454 L-type voltage-gated calcium channel complex ARBA:ARBA00090090 ACCEPT leaf (0) 0 human/CACNA1D GO:0006936 muscle contraction ARBA:ARBA00043367 KEEP_AS_NON_CORE general (21-200) 53 human/CACNA1D GO:0007154 cell communication ARBA:ARBA00028945 KEEP_AS_NON_CORE very general (>200 descendants) 1207 human/CACNA1D GO:0008092 cytoskeletal protein binding ARBA:ARBA00029239 MODIFY general (21-200) 53 NEEDS_MORE_SPECIFIC true but uninformative replacement term PMID:17110593 explicitly reports CaV1.3 association with alpha-actinin2 and its bridging relationship to SK2. GO:0051393 is already present as an experimental target annotation and resolves the partner class more precisely. The cytoskeletal bridge belongs to alpha-actinin2; no adapter activity is transferred to the channel. human/CACNA1D GO:0010959 regulation of metal ion transport ARBA:ARBA00084460 KEEP_AS_NON_CORE general (21-200) 104 human/CACNA1D GO:0030315 T-tubule ARBA:ARBA00087396 UNDECIDED specific (1-20) 1 human/CACNA1D GO:0050877 nervous system process ARBA:ARBA00029146 KEEP_AS_NON_CORE general (21-200) 194 human/CACNA1D GO:0051050 positive regulation of transport ARBA:ARBA00034593 KEEP_AS_NON_CORE very general (>200 descendants) 314 human/CACNA1D GO:0086007 voltage-gated calcium channel activity involved in cardiac muscle cell action potential ARBA:ARBA00089095 ACCEPT specific (1-20) 3 human/CACNA1F GO:0007601 visual perception ARBA:ARBA00086021 ACCEPT specific (1-20) 1 human/CACNA1F GO:0008331 high voltage-gated calcium channel activity ARBA:ARBA00091987 ACCEPT leaf (0) 0 human/CACNA1G GO:0008332 low voltage-gated calcium channel activity ARBA:ARBA00091989 ACCEPT leaf (0) 0 human/CACNA1G GO:0070509 calcium ion import ARBA:ARBA00085091 MODIFY specific (1-20) 1 NEEDS_MORE_SPECIFIC true but uninformative replacement term The general import process is consistent with CaV3.1 physiology. Human localization and electrophysiology in PMID:26715324, together with the existing GO:0098703 annotation, support calcium ion import across plasma membrane. human/CACNA1G GO:0097110 scaffold protein binding ARBA:ARBA00034605 KEEP_AS_NON_CORE leaf (0) 0 human/CACNB3 GO:0030315 T-tubule ARBA:ARBA00087396 UNDECIDED specific (1-20) 1 human/CAD GO:0055086 nucleobase-containing small molecule metabolic process ARBA:ARBA00027681 MODIFY very general (>200 descendants) 576 NEEDS_MORE_SPECIFIC true but uninformative replacement term The ARBA classification of nucleobase-containing small-molecule metabolism is compatible with CAD function. The official GO hierarchy places de novo UMP biosynthesis under this broader scope, and CAD directly catalyzes its first three steps. Replace the broad label with the already-established pathway term rather than treating correct ancestry as a false function. human/CAD GO:0072528 pyrimidine-containing compound biosynthetic process ARBA:ARBA00026919 MODIFY general (21-200) 57 NEEDS_MORE_SPECIFIC true but uninformative replacement term The ARBA classification of pyrimidine-containing compound biosynthesis is compatible with CAD function. The official GO hierarchy places de novo UMP biosynthesis under this broader scope, and CAD directly catalyzes its first three steps. Replace the broad label with the already-established pathway term rather than treating correct ancestry as a false function. human/CAD GO:0090407 organophosphate biosynthetic process ARBA:ARBA00029048 MODIFY very general (>200 descendants) 274 NEEDS_MORE_SPECIFIC true but uninformative replacement term The ARBA classification of organophosphate biosynthesis is compatible with CAD function. The official GO hierarchy places de novo UMP biosynthesis under this broader scope, and CAD directly catalyzes its first three steps. Replace the broad label with the already-established pathway term rather than treating correct ancestry as a false function. human/CALCA GO:0048018 receptor ligand activity ARBA:ARBA00028558 ACCEPT general (21-200) 34 human/CALCA GO:0097646 calcitonin family receptor signaling pathway ARBA:ARBA00050066 ACCEPT specific (1-20) 6 human/CALM1 GO:0002027 regulation of heart rate ARBA:ARBA00087882 ACCEPT specific (1-20) 17 human/CALM1 GO:0005246 calcium channel regulator activity ARBA:ARBA00085486 ACCEPT specific (1-20) 1 human/CALM1 GO:0005513 detection of calcium ion ARBA:ARBA00086881 ACCEPT leaf (0) 0 human/CALM1 GO:0005876 spindle microtubule ARBA:ARBA00033575 KEEP_AS_NON_CORE specific (1-20) 9 human/CALM1 GO:0010856 adenylate cyclase activator activity ARBA:ARBA00084977 KEEP_AS_NON_CORE leaf (0) 0 human/CALM1 GO:0010881 regulation of cardiac muscle contraction by regulation of the release of sequestered calcium ion ARBA:ARBA00084948 ACCEPT leaf (0) 0 human/CALM1 GO:0019901 protein kinase binding ARBA:ARBA00028598 MODIFY specific (1-20) 15 NEEDS_MORE_SPECIFIC true but uninformative replacement term Binding to CaMKII is mechanistically coupled to release of kinase autoinhibition, rather than an unspecified kinase association. Refine the broad electronic binding claim to the independently demonstrated protein serine/threonine kinase activator activity; this does not imply that every kinase bound by calmodulin is activated. human/CALM1 GO:0030017 sarcomere ARBA:ARBA00028261 ACCEPT specific (1-20) 12 human/CALM1 GO:0031432 titin binding ARBA:ARBA00085850 KEEP_AS_NON_CORE leaf (0) 0 human/CALM1 GO:0032465 regulation of cytokinesis ARBA:ARBA00084247 KEEP_AS_NON_CORE general (21-200) 34 human/CALM1 GO:0034704 calcium channel complex ARBA:ARBA00085266 ACCEPT specific (1-20) 6 human/CALM1 GO:0043539 protein serine/threonine kinase activator activity ARBA:ARBA00085523 ACCEPT specific (1-20) 2 human/CALM1 GO:0060291 long-term synaptic potentiation ARBA:ARBA00091239 KEEP_AS_NON_CORE leaf (0) 0 human/CALM1 GO:0072542 protein phosphatase activator activity ARBA:ARBA00090664 ACCEPT specific (1-20) 1 human/CALM1 GO:0097720 calcineurin-mediated signaling ARBA:ARBA00090525 ACCEPT specific (1-20) 1 human/CALM1 GO:1901844 regulation of cell communication by electrical coupling involved in cardiac conduction ARBA:ARBA00091451 ACCEPT specific (1-20) 2 human/CALM2 GO:0002027 regulation of heart rate ARBA:ARBA00087882 ACCEPT specific (1-20) 17 human/CALM2 GO:0005246 calcium channel regulator activity ARBA:ARBA00085486 ACCEPT specific (1-20) 1 human/CALM2 GO:0005513 detection of calcium ion ARBA:ARBA00086881 ACCEPT leaf (0) 0 human/CALM2 GO:0005876 spindle microtubule ARBA:ARBA00033575 KEEP_AS_NON_CORE specific (1-20) 9 human/CALM2 GO:0010856 adenylate cyclase activator activity ARBA:ARBA00084977 KEEP_AS_NON_CORE leaf (0) 0 human/CALM2 GO:0010881 regulation of cardiac muscle contraction by regulation of the release of sequestered calcium ion ARBA:ARBA00084948 ACCEPT leaf (0) 0 human/CALM2 GO:0019901 protein kinase binding ARBA:ARBA00028598 KEEP_AS_NON_CORE specific (1-20) 15 human/CALM2 GO:0030017 sarcomere ARBA:ARBA00028261 KEEP_AS_NON_CORE specific (1-20) 12 human/CALM2 GO:0031432 titin binding ARBA:ARBA00085850 KEEP_AS_NON_CORE leaf (0) 0 human/CALM2 GO:0032465 regulation of cytokinesis ARBA:ARBA00084247 KEEP_AS_NON_CORE general (21-200) 34 human/CALM2 GO:0034704 calcium channel complex ARBA:ARBA00085266 ACCEPT specific (1-20) 6 human/CALM2 GO:0043539 protein serine/threonine kinase activator activity ARBA:ARBA00085523 ACCEPT specific (1-20) 2 human/CALM2 GO:0060291 long-term synaptic potentiation ARBA:ARBA00091239 KEEP_AS_NON_CORE leaf (0) 0 human/CALM2 GO:0072542 protein phosphatase activator activity ARBA:ARBA00090664 ACCEPT specific (1-20) 1 human/CALM2 GO:0097720 calcineurin-mediated signaling ARBA:ARBA00090525 ACCEPT specific (1-20) 1 human/CALM2 GO:1901844 regulation of cell communication by electrical coupling involved in cardiac conduction ARBA:ARBA00091451 ACCEPT specific (1-20) 2 human/CALM3 GO:0002027 regulation of heart rate ARBA:ARBA00087882 ACCEPT specific (1-20) 17 human/CALM3 GO:0005246 calcium channel regulator activity ARBA:ARBA00085486 ACCEPT specific (1-20) 1 human/CALM3 GO:0005513 detection of calcium ion ARBA:ARBA00086881 ACCEPT leaf (0) 0 human/CALM3 GO:0005876 spindle microtubule ARBA:ARBA00033575 KEEP_AS_NON_CORE specific (1-20) 9 human/CALM3 GO:0010856 adenylate cyclase activator activity ARBA:ARBA00084977 KEEP_AS_NON_CORE leaf (0) 0 human/CALM3 GO:0010881 regulation of cardiac muscle contraction by regulation of the release of sequestered calcium ion ARBA:ARBA00084948 ACCEPT leaf (0) 0 human/CALM3 GO:0019901 protein kinase binding ARBA:ARBA00028598 MODIFY specific (1-20) 15 NEEDS_MORE_SPECIFIC true but uninformative replacement term Binding to CaMKII is mechanistically coupled to release of kinase autoinhibition, rather than an unspecified kinase association. Refine the broad electronic binding claim to the independently demonstrated protein serine/threonine kinase activator activity; this does not imply that every kinase bound by calmodulin is activated. human/CALM3 GO:0030017 sarcomere ARBA:ARBA00028261 ACCEPT specific (1-20) 12 human/CALM3 GO:0031432 titin binding ARBA:ARBA00085850 KEEP_AS_NON_CORE leaf (0) 0 human/CALM3 GO:0032465 regulation of cytokinesis ARBA:ARBA00084247 KEEP_AS_NON_CORE general (21-200) 34 human/CALM3 GO:0034704 calcium channel complex ARBA:ARBA00085266 ACCEPT specific (1-20) 6 human/CALM3 GO:0043539 protein serine/threonine kinase activator activity ARBA:ARBA00085523 ACCEPT specific (1-20) 2 human/CALM3 GO:0060291 long-term synaptic potentiation ARBA:ARBA00091239 KEEP_AS_NON_CORE leaf (0) 0 human/CALM3 GO:0072542 protein phosphatase activator activity ARBA:ARBA00090664 ACCEPT specific (1-20) 1 human/CALM3 GO:0097720 calcineurin-mediated signaling ARBA:ARBA00090525 ACCEPT specific (1-20) 1 human/CALM3 GO:1901844 regulation of cell communication by electrical coupling involved in cardiac conduction ARBA:ARBA00091451 ACCEPT specific (1-20) 2 human/CALR GO:0005737 cytoplasm ARBA:ARBA00026971 KEEP_AS_NON_CORE very general (>200 descendants) 1146 human/CALR GO:0012505 endomembrane system ARBA:ARBA00028953 MARK_AS_OVER_ANNOTATED very general (>200 descendants) 357 TOO_GENERAL true but uninformative Subsumed Subsumed by the more specific ER lumen annotation. human/CAMK2A GO:0005954 calcium- and calmodulin-dependent protein kinase complex ARBA:ARBA00088356 ACCEPT leaf (0) 0 human/CAMK2A GO:0030666 endocytic vesicle membrane ARBA:ARBA00026506 UNDECIDED specific (1-20) 9 human/CAMK2A GO:0042803 protein homodimerization activity ARBA:ARBA00027933 KEEP_AS_NON_CORE leaf (0) 0 human/CAMK2A GO:0060291 long-term synaptic potentiation ARBA:ARBA00091239 ACCEPT leaf (0) 0 human/CAPN3 GO:0008234 cysteine-type peptidase activity ARBA:ARBA00027409 MODIFY specific (1-20) 16 NEEDS_MORE_SPECIFIC true but uninformative replacement term The biochemical work, original molecular identification, and enzyme architecture support the specific calcium-dependent endopeptidase class. The broader cysteine peptidase assertion is not false, but GO:0004198 more accurately describes the reviewed activity. This refinement does not imply identical activity of every alternative product. human/CAPSL GO:0043226 organelle ARBA:ARBA00029065 KEEP_AS_NON_CORE very general (>200 descendants) 1881 human/CARD11 GO:0002376 immune system process ARBA:ARBA00027799 KEEP_AS_NON_CORE very general (>200 descendants) 673 human/CARD11 GO:0007165 signal transduction ARBA:ARBA00029050 KEEP_AS_NON_CORE very general (>200 descendants) 937 human/CARD11 GO:0032743 positive regulation of interleukin-2 production ARBA:ARBA00085753 KEEP_AS_NON_CORE leaf (0) 0 human/CARD11 GO:0050870 positive regulation of T cell activation ARBA:ARBA00029152 KEEP_AS_NON_CORE general (21-200) 43 human/CARMIL2 GO:0015629 actin cytoskeleton ARBA:ARBA00029230 ACCEPT general (21-200) 89 human/CARMIL2 GO:0160108 animal gross anatomical part developmental process ARBA:ARBA00098139 UNDECIDED very general (>200 descendants) 3010 human/CASK GO:0004385 GMP kinase activity ARBA:ARBA00086776 REMOVE leaf (0) 0 NONCATALYTIC_HOMOLOG wrong manual NONCATALYTIC_HOMOLOG GO:0004385 specifies ATP-dependent GMP-to-GDP catalysis. The C-terminal CASK-SH3GK construct lacked detectable guanylate kinase activity and GMP binding in the later biochemical study, with yeast guanylate kinase as a positive control. CASK protein phosphorylation uses its separate N-terminal kinase domain; it cannot rescue this electronic GMP-kinase assignment. The CASK-specific negative activity result and yeast-GK positive control were read in the official publisher Results/Fig. 1B of PMID:12482754, beyond its abstract-only cache; PSD95 mutational rescue and ligand-binding controls are not relabeled CASK experiments. human/CASK GO:0030054 cell junction ARBA:ARBA00028333 ACCEPT general (21-200) 189 human/CASP10 GO:0005737 cytoplasm ARBA:ARBA00026971 KEEP_AS_NON_CORE very general (>200 descendants) 1146 human/CASP10 GO:0051604 protein maturation ARBA:ARBA00026902 ACCEPT general (21-200) 74 human/CASP3 GO:0006915 apoptotic process ARBA:ARBA00027755 ACCEPT general (21-200) 115 human/CASP3 GO:0051604 protein maturation ARBA:ARBA00026902 ACCEPT general (21-200) 74 human/CASP3 GO:0072734 cellular response to staurosporine ARBA:ARBA00092857 KEEP_AS_NON_CORE leaf (0) 0 human/CASP4 GO:0051604 protein maturation ARBA:ARBA00026902 ACCEPT general (21-200) 74 human/CASP4 GO:0065003 protein-containing complex assembly ARBA:ARBA00029057 MODIFY very general (>200 descendants) 241 NEEDS_MORE_SPECIFIC true but uninformative replacement term The assembly CASP4 actually carries out is that of the non-canonical inflammasome, a specific child of this term that the gene already carries under both TAS and IDA evidence. human/CASP4 GO:0097193 intrinsic apoptotic signaling pathway ARBA:ARBA00028303 KEEP_AS_NON_CORE specific (1-20) 13 human/CASP6 GO:0051604 protein maturation ARBA:ARBA00026902 MODIFY general (21-200) 74 NEEDS_MORE_SPECIFIC true but uninformative replacement term General protein maturation should be narrowed to protein autoprocessing because the direct evidence here is CASP6 self-cleavage at Asp-179/Asp-193 during activation. human/CASP6 GO:0070269 pyroptotic inflammatory response ARBA:ARBA00091826 ACCEPT specific (1-20) 2 human/CASP6 GO:0072734 cellular response to staurosporine ARBA:ARBA00092857 REMOVE leaf (0) 0 UNSUPPORTED overreach manual UNSUPPORTED The manual CAFA row is from a DFF40/CAD paper that has no CASP6-specific evidence in the cached full text, and the parallel ARBA row is a reagent-specific apoptosis label rather than an informative CASP6 activity. human/CASP6 GO:0097193 intrinsic apoptotic signaling pathway ARBA:ARBA00028303 ACCEPT specific (1-20) 13 human/CASP7 GO:0009617 response to bacterium ARBA:ARBA00026494 MARK_AS_OVER_ANNOTATED general (21-200) 53 INDIRECT_EFFECT overreach downstream CASP7 can activate SMPD1 downstream of pore damage, but GO:0009617 is a diffuse stimulus-response term for a direct protease whose supported role is protein maturation in pore repair. human/CASP7 GO:0097194 execution phase of apoptosis ARBA:ARBA00090101 ACCEPT specific (1-20) 6 human/CASP8 GO:0002682 regulation of immune system process ARBA:ARBA00027003 KEEP_AS_NON_CORE very general (>200 descendants) 1028 human/CASP8 GO:0008625 extrinsic apoptotic signaling pathway via death domain receptors ARBA:ARBA00084513 ACCEPT specific (1-20) 3 human/CASP8 GO:0009967 positive regulation of signal transduction ARBA:ARBA00027202 KEEP_AS_NON_CORE very general (>200 descendants) 209 human/CASP8 GO:0030154 cell differentiation ARBA:ARBA00027429 KEEP_AS_NON_CORE very general (>200 descendants) 1345 human/CASP8 GO:0043009 chordate embryonic development ARBA:ARBA00027425 KEEP_AS_NON_CORE general (21-200) 101 human/CASP8 GO:0048513 animal organ development ARBA:ARBA00029247 KEEP_AS_NON_CORE very general (>200 descendants) 1888 human/CASP8 GO:0051604 protein maturation ARBA:ARBA00026902 ACCEPT general (21-200) 74 human/CASP9 GO:0006974 DNA damage response ARBA:ARBA00026271 MARK_AS_OVER_ANNOTATED general (21-200) 95 UNCLASSIFIED unclassified DNA damage and UV can signal into the intrinsic mitochondrial pathway, but an automated stimulus-response term turns a common upstream trigger into an asserted CASP9 biological process. human/CASP9 GO:0009411 response to UV ARBA:ARBA00028103 MARK_AS_OVER_ANNOTATED specific (1-20) 17 UNCLASSIFIED unclassified DNA damage and UV can signal into the intrinsic mitochondrial pathway, but an automated stimulus-response term turns a common upstream trigger into an asserted CASP9 biological process. human/CASP9 GO:0051604 protein maturation ARBA:ARBA00026902 ACCEPT general (21-200) 74 human/CASQ2 GO:0033017 sarcoplasmic reticulum membrane ARBA:ARBA00029138 ACCEPT specific (1-20) 4 human/CASQ2 GO:0051258 protein polymerization ARBA:ARBA00028914 ACCEPT specific (1-20) 12 human/CASQ2 GO:0051279 regulation of release of sequestered calcium ion into cytosol ARBA:ARBA00089315 ACCEPT specific (1-20) 10 human/CASR GO:1902533 positive regulation of intracellular signal transduction ARBA:ARBA00027124 ACCEPT general (21-200) 89 human/CBFB GO:0006355 regulation of DNA-templated transcription ARBA:ARBA00028138 ACCEPT general (21-200) 140 human/CBL GO:0050821 protein stabilization ARBA:ARBA00033884 UNDECIDED leaf (0) 0 human/CBL GO:0050860 negative regulation of T cell receptor signaling pathway ARBA:ARBA00091732 ACCEPT specific (1-20) 1 human/CBL GO:0050868 negative regulation of T cell activation ARBA:ARBA00091719 KEEP_AS_NON_CORE general (21-200) 37 human/CBL GO:0070534 protein K63-linked ubiquitination ARBA:ARBA00085191 ACCEPT leaf (0) 0 human/CBS GO:0050667 homocysteine metabolic process ARBA:ARBA00089512 ACCEPT specific (1-20) 4 human/CBS GO:0006534 cysteine metabolic process ARBA:ARBA00026351 ACCEPT leaf (0) 0 human/CBS GO:0044272 sulfur compound biosynthetic process ARBA:ARBA00028512 ACCEPT general (21-200) 74 human/CCM2 GO:0001570 vasculogenesis ARBA:ARBA00090144 KEEP_AS_NON_CORE specific (1-20) 4 human/CCM2 GO:0003158 endothelium development ARBA:ARBA00088444 KEEP_AS_NON_CORE general (21-200) 43 human/CCN6 GO:0050793 regulation of developmental process ARBA:ARBA00028689 KEEP_AS_NON_CORE very general (>200 descendants) 1542 human/CCNB1 GO:0005829 cytosol ARBA:ARBA00029243 ACCEPT general (21-200) 73 human/CCND1 GO:0000082 G1/S transition of mitotic cell cycle ARBA:ARBA00028571 ACCEPT leaf (0) 0 human/CCND1 GO:0061575 cyclin-dependent protein serine/threonine kinase activator activity ARBA:ARBA00091227 ACCEPT leaf (0) 0 human/CCND1 GO:1901992 positive regulation of mitotic cell cycle phase transition ARBA:ARBA00029089 ACCEPT specific (1-20) 8 human/CCND1 GO:2000045 regulation of G1/S transition of mitotic cell cycle ARBA:ARBA00033889 ACCEPT specific (1-20) 6 human/CCND2 GO:0000082 G1/S transition of mitotic cell cycle ARBA:ARBA00028571 ACCEPT leaf (0) 0 human/CCND2 GO:0061575 cyclin-dependent protein serine/threonine kinase activator activity ARBA:ARBA00091227 ACCEPT leaf (0) 0 human/CCND2 GO:1901992 positive regulation of mitotic cell cycle phase transition ARBA:ARBA00029089 ACCEPT specific (1-20) 8 human/CCND2 GO:2000045 regulation of G1/S transition of mitotic cell cycle ARBA:ARBA00033889 ACCEPT specific (1-20) 6 human/CCNO GO:0060271 cilium assembly ARBA:ARBA00027837 ACCEPT specific (1-20) 19 human/CCNO GO:0160108 animal gross anatomical part developmental process ARBA:ARBA00098139 KEEP_AS_NON_CORE very general (>200 descendants) 3010 human/CD247 GO:0098797 plasma membrane protein complex ARBA:ARBA00028841 ACCEPT very general (>200 descendants) 309 human/CD28 GO:0002376 immune system process ARBA:ARBA00027799 ACCEPT very general (>200 descendants) 673 human/CD28 GO:0050870 positive regulation of T cell activation ARBA:ARBA00029152 ACCEPT general (21-200) 43 human/CD2AP GO:0032991 protein-containing complex ARBA:ARBA00028902 KEEP_AS_NON_CORE very general (>200 descendants) 2083 human/CD320 GO:0016020 membrane ARBA:ARBA00028763 MODIFY very general (>200 descendants) 895 NEEDS_MORE_SPECIFIC true but uninformative replacement term CD320 has a membrane-spanning segment and is directly demonstrated at the cell surface. This refinement uses target evidence rather than treating the ARBA rule as an independent experiment. human/CD320 GO:0016192 vesicle-mediated transport ARBA:ARBA00028249 MODIFY very general (>200 descendants) 232 NEEDS_MORE_SPECIFIC true but uninformative replacement term CD320 captures extracellular transcobalamin-cobalamin and promotes its internalization; this supplies a specific mechanism for the broad electronic vesicle-transport annotation. It is a cargo receptor, not a vesicle motor or the enzyme that subsequently processes cobalamin. human/CD3D GO:0002376 immune system process ARBA:ARBA00027799 KEEP_AS_NON_CORE very general (>200 descendants) 673 human/CD3E GO:0009966 regulation of signal transduction ARBA:ARBA00027204 KEEP_AS_NON_CORE very general (>200 descendants) 696 human/CD3E GO:0010628 positive regulation of gene expression ARBA:ARBA00026655 MARK_AS_OVER_ANNOTATED general (21-200) 198 TOO_GENERAL true but uninformative broad Receptor-triggered reporter and expression readouts place CD3 epsilon upstream of transcriptional responses, but do not show that it directly regulates gene expression or occupies promoters. The broad ARBA inference projects a pathway output onto the receptor subunit and overstates CD3E's participation. human/CD3E GO:0042102 positive regulation of T cell proliferation ARBA:ARBA00085815 KEEP_AS_NON_CORE specific (1-20) 9 human/CD3E GO:0050852 T cell receptor signaling pathway ARBA:ARBA00091705 ACCEPT specific (1-20) 1 human/CD4 GO:0002684 positive regulation of immune system process ARBA:ARBA00027011 KEEP_AS_NON_CORE very general (>200 descendants) 392 human/CD4 GO:0050863 regulation of T cell activation ARBA:ARBA00029128 ACCEPT general (21-200) 124 human/CD4 GO:0051240 positive regulation of multicellular organismal process ARBA:ARBA00028891 KEEP_AS_NON_CORE very general (>200 descendants) 565 human/CD40 GO:0006952 defense response ARBA:ARBA00026315 KEEP_AS_NON_CORE general (21-200) 175 human/CD40 GO:0010468 regulation of gene expression ARBA:ARBA00028334 KEEP_AS_NON_CORE very general (>200 descendants) 874 human/CD40 GO:0051094 positive regulation of developmental process ARBA:ARBA00027577 KEEP_AS_NON_CORE very general (>200 descendants) 467 human/CD40 GO:0051240 positive regulation of multicellular organismal process ARBA:ARBA00028891 KEEP_AS_NON_CORE very general (>200 descendants) 565 human/CD40LG GO:0002682 regulation of immune system process ARBA:ARBA00027003 KEEP_AS_NON_CORE very general (>200 descendants) 1028 human/CD40LG GO:0005102 signaling receptor binding ARBA:ARBA00027239 MODIFY very general (>200 descendants) 380 NEEDS_MORE_SPECIFIC true but uninformative replacement term The generic receptor-binding prediction can be replaced with the directly supported receptor-specific term; human TRAP/CD40L binding to a soluble CD40 construct was assayed. human/CD40LG GO:0007154 cell communication ARBA:ARBA00028945 MODIFY very general (>200 descendants) 1207 NEEDS_MORE_SPECIFIC true but uninformative replacement term The electronic cell-communication annotation is too broad to describe the established ligand/receptor mechanism. Use the experimentally supported CD40 pathway. human/CD40LG GO:0010468 regulation of gene expression ARBA:ARBA00028334 KEEP_AS_NON_CORE very general (>200 descendants) 874 human/CD40LG GO:0023052 signaling ARBA:ARBA00026303 MODIFY very general (>200 descendants) 1141 NEEDS_MORE_SPECIFIC true but uninformative replacement term The generic electronic signaling assignment can be refined to the directly established cognate receptor pathway. human/CD46 GO:0016020 membrane ARBA:ARBA00028763 KEEP_AS_NON_CORE very general (>200 descendants) 895 human/CD46 GO:0050776 regulation of immune response ARBA:ARBA00028647 KEEP_AS_NON_CORE very general (>200 descendants) 505 human/CD47 GO:0002684 positive regulation of immune system process ARBA:ARBA00027011 KEEP_AS_NON_CORE very general (>200 descendants) 392 human/CD47 GO:0098609 cell-cell adhesion ARBA:ARBA00026305 ACCEPT general (21-200) 60 human/CD48 GO:0045321 leukocyte activation ARBA:ARBA00091994 ACCEPT general (21-200) 181 human/CD70 GO:0042110 T cell activation ARBA:ARBA00085932 ACCEPT general (21-200) 87 human/CD70 GO:0046651 lymphocyte proliferation ARBA:ARBA00091995 MODIFY specific (1-20) 19 NEEDS_MORE_SPECIFIC true but uninformative replacement term The broad electronic lymphocyte-proliferation term does not distinguish cell type or the ligand’s signaling role. Human CD70/CD27 experiments directly support a positive T-cell proliferative costimulus. This source-specific refinement concerns forward signaling to T cells; the separate non-core B-cell proliferation assertion is supported by independent CD70 reverse-signaling evidence in its stated experimental contexts. human/CD79B GO:0002376 immune system process ARBA:ARBA00027799 MODIFY very general (>200 descendants) 673 NEEDS_MORE_SPECIFIC true but uninformative replacement term The broad electronic immune-system term is compatible with CD79B biology but can be made more informative. CD79B is an integral signaling chain of the BCR; human receptor structure and receptor-loss/rescue experiments support the named pathway. human/CD79B GO:0007165 signal transduction ARBA:ARBA00029050 MODIFY very general (>200 descendants) 937 NEEDS_MORE_SPECIFIC true but uninformative replacement term The original immune-response or signal-transduction annotation describes the correct general biology. The directly supported role is the signaling contribution of CD79B within the BCR complex, for which a specific existing process term is available. This does not assign antigen binding or intrinsic kinase catalysis to CD79B. human/CD86 GO:0007165 signal transduction ARBA:ARBA00029050 KEEP_AS_NON_CORE very general (>200 descendants) 937 human/CD86 GO:0008284 positive regulation of cell population proliferation ARBA:ARBA00027538 MODIFY general (21-200) 85 NEEDS_MORE_SPECIFIC true but uninformative replacement term The proliferation CD86 promotes is specifically T cell proliferation (costimulation with TCR signal). Replace with positive regulation of T cell proliferation (GO:0042102). human/CD86 GO:0009967 positive regulation of signal transduction ARBA:ARBA00027202 KEEP_AS_NON_CORE very general (>200 descendants) 209 human/CD86 GO:0046649 lymphocyte activation ARBA:ARBA00091981 MODIFY general (21-200) 144 NEEDS_MORE_SPECIFIC true but uninformative replacement term As for the T cell activation IDA, CD86 acts by providing a costimulatory signal; the specific process is T cell costimulation (GO:0031295). human/CD86 GO:0050778 positive regulation of immune response ARBA:ARBA00028646 ACCEPT very general (>200 descendants) 217 human/CD8A GO:0007166 cell surface receptor signaling pathway ARBA:ARBA00029053 ACCEPT very general (>200 descendants) 403 human/CD8A GO:0009897 external side of plasma membrane ARBA:ARBA00043397 ACCEPT specific (1-20) 4 human/CD8A GO:0042110 T cell activation ARBA:ARBA00085932 ACCEPT general (21-200) 87 human/CD8A GO:0043235 receptor complex ARBA:ARBA00029086 ACCEPT general (21-200) 113 human/CDA GO:0005737 cytoplasm ARBA:ARBA00026971 MARK_AS_OVER_ANNOTATED very general (>200 descendants) 1146 TOO_GENERAL true but uninformative broad """cytoplasm"" is a broad parent of the experimentally supported ""cytosol""; the specific term is preferred, so the general electronic call is non-informative here." human/CDA GO:0009173 pyrimidine ribonucleoside monophosphate metabolic process ARBA:ARBA00090981 MARK_AS_OVER_ANNOTATED specific (1-20) 16 UNCLASSIFIED unclassified CDA's direct substrate is the nucleoside, not the nucleoside monophosphate; deoxycytidine/cytidine catabolic process terms already capture the correct process. Electronic term is imprecise about substrate level. human/CDA GO:0009218 pyrimidine ribonucleotide metabolic process ARBA:ARBA00090558 MARK_AS_OVER_ANNOTATED general (21-200) 38 TOO_GENERAL true but uninformative general Over-general/imprecise: CDA operates on (deoxy)cytidine nucleosides; nucleotide-level pyrimidine metabolism is not its direct activity. human/CDA GO:0042802 identical protein binding ARBA:ARBA00027930 KEEP_AS_NON_CORE specific (1-20) 1 human/CDC14A GO:0005815 microtubule organizing center ARBA:ARBA00029135 MODIFY general (21-200) 42 NEEDS_MORE_SPECIFIC true but uninformative replacement term Human experiments support the more informative centrosome compartment. Preserve the original electronic source while proposing this location refinement. human/CDC25C GO:0000086 G2/M transition of mitotic cell cycle ARBA:ARBA00090227 ACCEPT leaf (0) 0 human/CDC25C GO:0008283 cell population proliferation ARBA:ARBA00035743 KEEP_AS_NON_CORE general (21-200) 163 human/CDC42 GO:0009653 anatomical structure morphogenesis ARBA:ARBA00026583 KEEP_AS_NON_CORE very general (>200 descendants) 1501 human/CDC42 GO:0051130 positive regulation of cellular component organization ARBA:ARBA00026675 KEEP_AS_NON_CORE very general (>200 descendants) 291 human/CDC42 GO:0160108 animal gross anatomical part developmental process ARBA:ARBA00098139 KEEP_AS_NON_CORE very general (>200 descendants) 3010 human/CDH1 GO:0030054 cell junction ARBA:ARBA00028333 KEEP_AS_NON_CORE general (21-200) 189 human/CDH1 GO:0034329 cell junction assembly ARBA:ARBA00029029 KEEP_AS_NON_CORE general (21-200) 33 human/CDH3 GO:0030054 cell junction ARBA:ARBA00028333 ACCEPT general (21-200) 189 human/CDHR1 GO:0045494 photoreceptor cell maintenance ARBA:ARBA00085416 ACCEPT leaf (0) 0 human/CDK13 GO:0000307 cyclin-dependent protein kinase holoenzyme complex ARBA:ARBA00027596 ACCEPT general (21-200) 29 human/CDK13 GO:0032968 positive regulation of transcription elongation by RNA polymerase II ARBA:ARBA00033872 ACCEPT leaf (0) 0 human/CDK4 GO:0000082 G1/S transition of mitotic cell cycle ARBA:ARBA00028571 ACCEPT leaf (0) 0 human/CDK4 GO:0048146 positive regulation of fibroblast proliferation ARBA:ARBA00089974 KEEP_AS_NON_CORE specific (1-20) 2 human/CDK5 GO:0007409 axonogenesis ARBA:ARBA00026520 ACCEPT general (21-200) 78 human/CDK5 GO:0051649 establishment of localization in cell ARBA:ARBA00028679 KEEP_AS_NON_CORE very general (>200 descendants) 411 human/CDK5 GO:0051726 regulation of cell cycle ARBA:ARBA00029144 ACCEPT very general (>200 descendants) 377 human/CDKN1B GO:0007165 signal transduction ARBA:ARBA00029050 KEEP_AS_NON_CORE very general (>200 descendants) 937 human/CDKN1B GO:0008285 negative regulation of cell population proliferation ARBA:ARBA00027539 ACCEPT general (21-200) 81 human/CDKN1B GO:0045926 negative regulation of growth ARBA:ARBA00028151 KEEP_AS_NON_CORE general (21-200) 47 human/CDKN1B GO:1901990 regulation of mitotic cell cycle phase transition ARBA:ARBA00029095 ACCEPT general (21-200) 32 human/CDKN1C GO:0045892 negative regulation of DNA-templated transcription ARBA:ARBA00029084 MODIFY general (21-200) 39 NEEDS_MORE_SPECIFIC true but uninformative replacement term Refine the broad ARBA process to RNAPII transcriptional repression. Human p57 depletion increases histone H4 output in HeLa cells, and human WI38 reporter experiments show inhibition. Separate RNAPII-CTD experiments combine endogenous human-cell evidence with mouse-p57 overexpression, rather than establishing direct DNA recognition by p57. human/CDKN2A GO:0004861 cyclin-dependent protein serine/threonine kinase inhibitor activity ARBA:ARBA00087839 ACCEPT leaf (0) 0 human/CDKN2A GO:0090398 cellular senescence ARBA:ARBA00086844 ACCEPT specific (1-20) 3 human/CDKN2A GO:2000045 regulation of G1/S transition of mitotic cell cycle ARBA:ARBA00033889 ACCEPT specific (1-20) 6 human/CDO1 GO:0006790 sulfur compound metabolic process ARBA:ARBA00028021 ACCEPT general (21-200) 190 human/CDT1 GO:0090329 regulation of DNA-templated DNA replication ARBA:ARBA00026722 ACCEPT general (21-200) 35 human/CEBPA GO:0090575 RNA polymerase II transcription regulator complex ARBA:ARBA00028248 KEEP_AS_NON_CORE general (21-200) 44 human/CEP120 GO:0010824 regulation of centrosome duplication ARBA:ARBA00084913 MODIFY specific (1-20) 6 NEEDS_MORE_SPECIFIC true but uninformative replacement term The directionless electronic regulation term can be refined to positive regulation of centrosome duplication. Loss/depletion impairs duplication and rescue restores it; independent human experiments establish a centriole-construction role. Quiescent-cell restraint of premature PCM accumulation is a different outcome and does not reverse this duplication-specific direction. human/CEP120 GO:0032880 regulation of protein localization ARBA:ARBA00026609 MODIFY very general (>200 descendants) 220 NEEDS_MORE_SPECIFIC true but uninformative replacement term Refine the broad localization term to GO:1904779 regulation of protein localization to centrosome. Human RPE1 CEP120 loss reduces recruitment of C2CD3, TALPID3, SPICE, centrobin, POC1B and POC5 to nascent centrioles in PMID:30988386 Figures 2–3. In contrast, quiescent mouse fibroblasts in PMID:29741480 Figures 2–4 accumulate excess centrosomal PCM after Cep120 depletion; rescue and overexpression support a restraining role in that context. The shared destination is the centrosome, while the direction-neutral parent preserves these distinct effects and their species/cell-state limits. The original ARBA assertion is unchanged; its historical rule is not reconstructed. human/CEP120 GO:0090068 positive regulation of cell cycle process ARBA:ARBA00029176 MODIFY general (21-200) 104 NEEDS_MORE_SPECIFIC true but uninformative replacement term The broad electronic positive-cell-cycle-process term is best expressed as the demonstrated positive regulation of centrosome duplication. The evidence concerns centriole construction within the centrosome cycle, not a generic stimulation of every cell-cycle phase or an inferred autonomous mitogenic activity. human/CEP120 GO:1902117 positive regulation of organelle assembly ARBA:ARBA00088865 MODIFY specific (1-20) 18 NEEDS_MORE_SPECIFIC true but uninformative replacement term The electronic organelle-assembly term is broader than the documented work. Refine it to positive regulation of centriole elongation and positive regulation of cilium assembly, supported by human depletion/overexpression, knockout/rescue and recruitment experiments. These are source-specific refinements of an existing assertion, not new process additions. human/CEP164 GO:0097539 ciliary transition fiber ARBA:ARBA00091172 ACCEPT leaf (0) 0 human/CEPT1 GO:0005737 cytoplasm ARBA:ARBA00026971 MARK_AS_OVER_ANNOTATED very general (>200 descendants) 1146 TOO_GENERAL true but uninformative generic The specific ER-membrane / nuclear-membrane localizations supersede this generic term, which mislocalizes an integral membrane enzyme to the soluble cytoplasm. human/CEPT1 GO:0012505 endomembrane system ARBA:ARBA00028953 MARK_AS_OVER_ANNOTATED very general (>200 descendants) 357 TOO_GENERAL true but uninformative broad The specific ER/nuclear membrane annotations supersede this broad grouping term. human/CFAP221 GO:0015630 microtubule cytoskeleton ARBA:ARBA00029268 KEEP_AS_NON_CORE general (21-200) 108 human/CFAP43 GO:0003341 cilium movement ARBA:ARBA00034388 ACCEPT specific (1-20) 10 human/CFH GO:0006954 inflammatory response ARBA:ARBA00045028 MODIFY general (21-200) 70 NEEDS_MORE_SPECIFIC true but uninformative replacement term Independent human-FH treatment and oxidation-epitope experiments support suppression of inflammatory responses. Refine the electronic broad term to this demonstrated direction, without claiming that its exact historical ARBA training path was reconstructed. human/CFH GO:0006957 complement activation, alternative pathway ARBA:ARBA00086627 MODIFY leaf (0) 0 NEEDS_MORE_SPECIFIC true but uninformative replacement term Human factor H supports C3b inactivation by factor I and accelerates C3bBb decay. Negative regulation of alternative-pathway activation expresses this established role more accurately than the broad activation term. The original ARBA identifier and evidence type remain unchanged. human/CFH GO:0008201 heparin binding ARBA:ARBA00027326 ACCEPT leaf (0) 0 human/CFH GO:0022008 neurogenesis ARBA:ARBA00028404 KEEP_AS_NON_CORE very general (>200 descendants) 439 human/CFH GO:0030449 regulation of complement activation ARBA:ARBA00027989 MODIFY specific (1-20) 14 NEEDS_MORE_SPECIFIC true but uninformative replacement term Refine this broad electronic regulation term using direct human factor-I cofactor and convertase-decay evidence. Preserve the original ARBA source object; this is a target-function refinement, not a claim that the historical rule path was independently reconstructed. human/CFH GO:0048468 cell development ARBA:ARBA00028665 KEEP_AS_NON_CORE very general (>200 descendants) 672 human/CFL2 GO:0008154 actin polymerization or depolymerization ARBA:ARBA00028283 ACCEPT specific (1-20) 3 human/CFLAR GO:0008047 enzyme activator activity ARBA:ARBA00029040 MODIFY general (21-200) 58 NEEDS_MORE_SPECIFIC true but uninformative replacement term FLIP(L) can promote limited initiator-caspase activation in heterodimers, so GO:0140608 is more specific than generic enzyme activator activity. human/CFLAR GO:0060544 regulation of necroptotic process ARBA:ARBA00090640 ACCEPT specific (1-20) 2 human/CFLAR GO:2001237 negative regulation of extrinsic apoptotic signaling pathway ARBA:ARBA00087856 MODIFY specific (1-20) 4 NEEDS_MORE_SPECIFIC true but uninformative replacement term The canonical inhibitory activity of c-FLIP is at FAS, TNFR1, and TRAIL receptor complexes, making GO:1902042 more informative than the broader extrinsic-apoptosis parent. human/CFTR GO:0005737 cytoplasm ARBA:ARBA00026971 KEEP_AS_NON_CORE very general (>200 descendants) 1146 human/CFTR GO:0015701 bicarbonate transport ARBA:ARBA00034575 ACCEPT specific (1-20) 10 human/CFTR GO:0098660 obsolete inorganic ion transmembrane transport ARBA:ARBA00026667 MODIFY leaf (0) 0 OTHER_TERM different term needed replacement term The official current response marks the original ID obsolete, but the original machine term is preserved. Independently measured monatomic-ion movement supports GO:0034220; this is a semantic update, not evidence that CFTR lacks the old process. human/CHCHD4 GO:0005739 mitochondrion ARBA:ARBA00026962 MARK_AS_OVER_ANNOTATED general (21-200) 70 TOO_GENERAL true but uninformative Subsumed Subsumed by mitochondrial intermembrane space annotation. human/CHCHD4 GO:0033108 mitochondrial respiratory chain complex assembly ARBA:ARBA00092694 KEEP_AS_NON_CORE specific (1-20) 6 human/CHD2 GO:0006338 chromatin remodeling ARBA:ARBA00027994 ACCEPT very general (>200 descendants) 235 human/CHD3 GO:0005654 nucleoplasm ARBA:ARBA00026290 ACCEPT general (21-200) 65 human/CHD7 GO:0001701 in utero embryonic development ARBA:ARBA00089616 KEEP_AS_NON_CORE general (21-200) 31 human/CHD7 GO:0003007 heart morphogenesis ARBA:ARBA00086699 KEEP_AS_NON_CORE general (21-200) 98 human/CHD7 GO:0005654 nucleoplasm ARBA:ARBA00026290 ACCEPT general (21-200) 65 human/CHD7 GO:0007417 central nervous system development ARBA:ARBA00026561 KEEP_AS_NON_CORE very general (>200 descendants) 464 human/CHD7 GO:0021545 cranial nerve development ARBA:ARBA00085097 KEEP_AS_NON_CORE general (21-200) 105 human/CHD7 GO:0042472 inner ear morphogenesis ARBA:ARBA00087234 KEEP_AS_NON_CORE specific (1-20) 17 human/CHD7 GO:0043010 camera-type eye development ARBA:ARBA00084629 KEEP_AS_NON_CORE general (21-200) 60 human/CHD7 GO:0043584 nose development ARBA:ARBA00085692 KEEP_AS_NON_CORE specific (1-20) 3 human/CHD7 GO:0048806 genitalia development ARBA:ARBA00090613 KEEP_AS_NON_CORE specific (1-20) 17 human/CHD7 GO:0050877 nervous system process ARBA:ARBA00029146 KEEP_AS_NON_CORE general (21-200) 194 human/CHD7 GO:0051049 regulation of transport ARBA:ARBA00027251 UNDECIDED very general (>200 descendants) 960 human/CHD7 GO:0060021 roof of mouth development ARBA:ARBA00089452 KEEP_AS_NON_CORE specific (1-20) 6 human/CHD7 GO:0060173 limb development ARBA:ARBA00091631 KEEP_AS_NON_CORE general (21-200) 33 human/CHD7 GO:0060322 head development ARBA:ARBA00028411 KEEP_AS_NON_CORE very general (>200 descendants) 367 human/CHD8 GO:0005654 nucleoplasm ARBA:ARBA00026290 ACCEPT general (21-200) 65 human/CHEK1 GO:0042770 signal transduction in response to DNA damage ARBA:ARBA00088532 ACCEPT specific (1-20) 7 human/CHEK1 GO:1901988 negative regulation of cell cycle phase transition ARBA:ARBA00029277 ACCEPT general (21-200) 45 human/CHEK2 GO:0008630 intrinsic apoptotic signaling pathway in response to DNA damage ARBA:ARBA00027191 ACCEPT specific (1-20) 1 human/CHEK2 GO:0030330 DNA damage response, signal transduction by p53 class mediator ARBA:ARBA00093717 ACCEPT leaf (0) 0 human/CHMP1A GO:0000776 kinetochore ARBA:ARBA00027576 ACCEPT specific (1-20) 11 human/CHMP1A GO:0001778 plasma membrane repair ARBA:ARBA00033547 ACCEPT leaf (0) 0 human/CHMP1A GO:0005643 nuclear pore ARBA:ARBA00026270 KEEP_AS_NON_CORE specific (1-20) 9 human/CHMP1A GO:0005765 lysosomal membrane ARBA:ARBA00028563 ACCEPT specific (1-20) 12 human/CHMP1A GO:0005828 kinetochore microtubule ARBA:ARBA00033604 KEEP_AS_NON_CORE specific (1-20) 1 human/CHMP1A GO:0007080 mitotic metaphase chromosome alignment ARBA:ARBA00033550 KEEP_AS_NON_CORE specific (1-20) 7 human/CHMP1A GO:0030496 midbody ARBA:ARBA00033509 ACCEPT specific (1-20) 1 human/CHMP1A GO:0031468 nuclear membrane reassembly ARBA:ARBA00033562 ACCEPT specific (1-20) 7 human/CHMP1A GO:0032585 multivesicular body membrane ARBA:ARBA00033600 ACCEPT specific (1-20) 1 human/CHMP1A GO:0039702 viral budding via host ESCRT complex ARBA:ARBA00028526 KEEP_AS_NON_CORE leaf (0) 0 human/CHMP1A GO:0043162 ubiquitin-dependent protein catabolic process via the multivesicular body sorting pathway ARBA:ARBA00033490 ACCEPT specific (1-20) 1 human/CHMP1A GO:0046761 viral budding from plasma membrane ARBA:ARBA00033532 KEEP_AS_NON_CORE leaf (0) 0 human/CHMP1A GO:0061952 midbody abscission ARBA:ARBA00029210 ACCEPT leaf (0) 0 human/CHMP1A GO:0071985 multivesicular body sorting pathway ARBA:ARBA00033501 ACCEPT specific (1-20) 6 human/CHMP1A GO:0097352 autophagosome maturation ARBA:ARBA00033540 ACCEPT specific (1-20) 1 human/CHMP1A GO:1901673 regulation of mitotic spindle assembly ARBA:ARBA00033492 KEEP_AS_NON_CORE specific (1-20) 3 human/CHMP1A GO:1902774 late endosome to lysosome transport ARBA:ARBA00033593 ACCEPT specific (1-20) 1 human/CHMP1A GO:1904930 amphisome membrane ARBA:ARBA00033513 ACCEPT leaf (0) 0 human/CHMP1B GO:0000776 kinetochore ARBA:ARBA00027576 KEEP_AS_NON_CORE specific (1-20) 11 human/CHMP1B GO:0001778 plasma membrane repair ARBA:ARBA00033547 ACCEPT leaf (0) 0 human/CHMP1B GO:0005643 nuclear pore ARBA:ARBA00026270 ACCEPT specific (1-20) 9 human/CHMP1B GO:0005765 lysosomal membrane ARBA:ARBA00028563 ACCEPT specific (1-20) 12 human/CHMP1B GO:0005828 kinetochore microtubule ARBA:ARBA00033604 KEEP_AS_NON_CORE specific (1-20) 1 human/CHMP1B GO:0007080 mitotic metaphase chromosome alignment ARBA:ARBA00033550 KEEP_AS_NON_CORE specific (1-20) 7 human/CHMP1B GO:0030496 midbody ARBA:ARBA00033509 ACCEPT specific (1-20) 1 human/CHMP1B GO:0031468 nuclear membrane reassembly ARBA:ARBA00033562 ACCEPT specific (1-20) 7 human/CHMP1B GO:0032585 multivesicular body membrane ARBA:ARBA00033600 ACCEPT specific (1-20) 1 human/CHMP1B GO:0039702 viral budding via host ESCRT complex ARBA:ARBA00028526 KEEP_AS_NON_CORE leaf (0) 0 human/CHMP1B GO:0043162 ubiquitin-dependent protein catabolic process via the multivesicular body sorting pathway ARBA:ARBA00033490 ACCEPT specific (1-20) 1 human/CHMP1B GO:0046761 viral budding from plasma membrane ARBA:ARBA00033532 KEEP_AS_NON_CORE leaf (0) 0 human/CHMP1B GO:0061952 midbody abscission ARBA:ARBA00029210 ACCEPT leaf (0) 0 human/CHMP1B GO:0071985 multivesicular body sorting pathway ARBA:ARBA00033501 ACCEPT specific (1-20) 6 human/CHMP1B GO:0097352 autophagosome maturation ARBA:ARBA00033540 ACCEPT specific (1-20) 1 human/CHMP1B GO:1901673 regulation of mitotic spindle assembly ARBA:ARBA00033492 KEEP_AS_NON_CORE specific (1-20) 3 human/CHMP1B GO:1902774 late endosome to lysosome transport ARBA:ARBA00033593 ACCEPT specific (1-20) 1 human/CHMP1B GO:1904930 amphisome membrane ARBA:ARBA00033513 ACCEPT leaf (0) 0 human/CHMP2A GO:0032585 multivesicular body membrane ARBA:ARBA00033600 ACCEPT specific (1-20) 1 human/CHMP2A GO:0071985 multivesicular body sorting pathway ARBA:ARBA00033501 ACCEPT specific (1-20) 6 human/CHMP2A GO:0043162 ubiquitin-dependent protein catabolic process via the multivesicular body sorting pathway ARBA:ARBA00033490 ACCEPT specific (1-20) 1 human/CHMP2A GO:1902774 late endosome to lysosome transport ARBA:ARBA00033593 ACCEPT specific (1-20) 1 human/CHMP2A GO:0061952 midbody abscission ARBA:ARBA00029210 ACCEPT leaf (0) 0 human/CHMP2A GO:0030496 midbody ARBA:ARBA00033509 ACCEPT specific (1-20) 1 human/CHMP2A GO:0031468 nuclear membrane reassembly ARBA:ARBA00033562 ACCEPT specific (1-20) 7 human/CHMP2A GO:0039702 viral budding via host ESCRT complex ARBA:ARBA00028526 ACCEPT leaf (0) 0 human/CHMP2A GO:0046761 viral budding from plasma membrane ARBA:ARBA00033532 ACCEPT leaf (0) 0 human/CHMP2A GO:0097352 autophagosome maturation ARBA:ARBA00033540 ACCEPT specific (1-20) 1 human/CHMP2A GO:1904930 amphisome membrane ARBA:ARBA00033513 ACCEPT leaf (0) 0 human/CHMP2A GO:0001778 plasma membrane repair ARBA:ARBA00033547 ACCEPT leaf (0) 0 human/CHMP2A GO:0005765 lysosomal membrane ARBA:ARBA00028563 ACCEPT specific (1-20) 12 human/CHMP2A GO:0000776 kinetochore ARBA:ARBA00027576 KEEP_AS_NON_CORE specific (1-20) 11 human/CHMP2A GO:0005828 kinetochore microtubule ARBA:ARBA00033604 KEEP_AS_NON_CORE specific (1-20) 1 human/CHMP2A GO:0005643 nuclear pore ARBA:ARBA00026270 KEEP_AS_NON_CORE specific (1-20) 9 human/CHMP2A GO:0007080 mitotic metaphase chromosome alignment ARBA:ARBA00033550 KEEP_AS_NON_CORE specific (1-20) 7 human/CHMP2A GO:1901673 regulation of mitotic spindle assembly ARBA:ARBA00033492 KEEP_AS_NON_CORE specific (1-20) 3 human/CHMP2B GO:0000776 kinetochore ARBA:ARBA00027576 UNDECIDED specific (1-20) 11 human/CHMP2B GO:0001778 plasma membrane repair ARBA:ARBA00033547 ACCEPT leaf (0) 0 human/CHMP2B GO:0005643 nuclear pore ARBA:ARBA00026270 MODIFY specific (1-20) 9 TOO_SPECIFIC overreach replacement term GO:0005643 denotes the nuclear pore complex. Full PMID:26040713 Figures 1A/1B and Extended Data Figure 1A directly localize endogenous human CHMP2B to the reforming nuclear envelope; the separate CHMP2A ultrastructural analysis distinguishes non-NPC membrane openings. The broader envelope location is positively supported, while the original NPC incorporation basis remains unresolved. The historical source is unchanged; this recommendation does not manufacture a new relation or disprove another NPC-associated pool. human/CHMP2B GO:0005765 lysosomal membrane ARBA:ARBA00028563 UNDECIDED specific (1-20) 12 human/CHMP2B GO:0005828 kinetochore microtubule ARBA:ARBA00033604 UNDECIDED specific (1-20) 1 human/CHMP2B GO:0007080 mitotic metaphase chromosome alignment ARBA:ARBA00033550 KEEP_AS_NON_CORE specific (1-20) 7 human/CHMP2B GO:0030496 midbody ARBA:ARBA00033509 ACCEPT specific (1-20) 1 human/CHMP2B GO:0031468 nuclear membrane reassembly ARBA:ARBA00033562 ACCEPT specific (1-20) 7 human/CHMP2B GO:0032585 multivesicular body membrane ARBA:ARBA00033600 ACCEPT specific (1-20) 1 human/CHMP2B GO:0039702 viral budding via host ESCRT complex ARBA:ARBA00028526 KEEP_AS_NON_CORE leaf (0) 0 human/CHMP2B GO:0043162 ubiquitin-dependent protein catabolic process via the multivesicular body sorting pathway ARBA:ARBA00033490 KEEP_AS_NON_CORE specific (1-20) 1 human/CHMP2B GO:0046761 viral budding from plasma membrane ARBA:ARBA00033532 KEEP_AS_NON_CORE leaf (0) 0 human/CHMP2B GO:0061952 midbody abscission ARBA:ARBA00029210 ACCEPT leaf (0) 0 human/CHMP2B GO:0071985 multivesicular body sorting pathway ARBA:ARBA00033501 ACCEPT specific (1-20) 6 human/CHMP2B GO:0097352 autophagosome maturation ARBA:ARBA00033540 KEEP_AS_NON_CORE specific (1-20) 1 human/CHMP2B GO:1901673 regulation of mitotic spindle assembly ARBA:ARBA00033492 KEEP_AS_NON_CORE specific (1-20) 3 human/CHMP2B GO:1902774 late endosome to lysosome transport ARBA:ARBA00033593 KEEP_AS_NON_CORE specific (1-20) 1 human/CHMP2B GO:1904930 amphisome membrane ARBA:ARBA00033513 UNDECIDED leaf (0) 0 human/CHMP3 GO:0000776 kinetochore ARBA:ARBA00027576 ACCEPT specific (1-20) 11 human/CHMP3 GO:0001778 plasma membrane repair ARBA:ARBA00033547 ACCEPT leaf (0) 0 human/CHMP3 GO:0005643 nuclear pore ARBA:ARBA00026270 KEEP_AS_NON_CORE specific (1-20) 9 human/CHMP3 GO:0005765 lysosomal membrane ARBA:ARBA00028563 ACCEPT specific (1-20) 12 human/CHMP3 GO:0005828 kinetochore microtubule ARBA:ARBA00033604 KEEP_AS_NON_CORE specific (1-20) 1 human/CHMP3 GO:0032585 multivesicular body membrane ARBA:ARBA00033600 ACCEPT specific (1-20) 1 human/CHMP3 GO:0039702 viral budding via host ESCRT complex ARBA:ARBA00028526 ACCEPT leaf (0) 0 human/CHMP3 GO:0043162 ubiquitin-dependent protein catabolic process via the multivesicular body sorting pathway ARBA:ARBA00033490 ACCEPT specific (1-20) 1 human/CHMP3 GO:0046761 viral budding from plasma membrane ARBA:ARBA00033532 ACCEPT leaf (0) 0 human/CHMP3 GO:0061952 midbody abscission ARBA:ARBA00029210 ACCEPT leaf (0) 0 human/CHMP3 GO:0071985 multivesicular body sorting pathway ARBA:ARBA00033501 ACCEPT specific (1-20) 6 human/CHMP3 GO:0097352 autophagosome maturation ARBA:ARBA00033540 ACCEPT specific (1-20) 1 human/CHMP3 GO:1902774 late endosome to lysosome transport ARBA:ARBA00033593 ACCEPT specific (1-20) 1 human/CHMP3 GO:1904930 amphisome membrane ARBA:ARBA00033513 ACCEPT leaf (0) 0 human/CHMP4A GO:0000776 kinetochore ARBA:ARBA00027576 KEEP_AS_NON_CORE specific (1-20) 11 human/CHMP4A GO:0001778 plasma membrane repair ARBA:ARBA00033547 KEEP_AS_NON_CORE leaf (0) 0 human/CHMP4A GO:0005643 nuclear pore ARBA:ARBA00026270 KEEP_AS_NON_CORE specific (1-20) 9 human/CHMP4A GO:0005765 lysosomal membrane ARBA:ARBA00028563 ACCEPT specific (1-20) 12 human/CHMP4A GO:0005828 kinetochore microtubule ARBA:ARBA00033604 KEEP_AS_NON_CORE specific (1-20) 1 human/CHMP4A GO:0007080 mitotic metaphase chromosome alignment ARBA:ARBA00033550 KEEP_AS_NON_CORE specific (1-20) 7 human/CHMP4A GO:0030496 midbody ARBA:ARBA00033509 KEEP_AS_NON_CORE specific (1-20) 1 human/CHMP4A GO:0031468 nuclear membrane reassembly ARBA:ARBA00033562 KEEP_AS_NON_CORE specific (1-20) 7 human/CHMP4A GO:0032585 multivesicular body membrane ARBA:ARBA00033600 ACCEPT specific (1-20) 1 human/CHMP4A GO:0036258 multivesicular body assembly ARBA:ARBA00027035 ACCEPT leaf (0) 0 human/CHMP4A GO:0039702 viral budding via host ESCRT complex ARBA:ARBA00028526 KEEP_AS_NON_CORE leaf (0) 0 human/CHMP4A GO:0042803 protein homodimerization activity ARBA:ARBA00027933 MODIFY leaf (0) 0 OTHER_TERM different term needed replacement term CHMP4A forms curved ESCRT-III filaments/polymers that bend membranes; homodimer or identical-protein binding terms are weaker molecular descriptions. human/CHMP4A GO:0043162 ubiquitin-dependent protein catabolic process via the multivesicular body sorting pathway ARBA:ARBA00033490 ACCEPT specific (1-20) 1 human/CHMP4A GO:0046761 viral budding from plasma membrane ARBA:ARBA00033532 KEEP_AS_NON_CORE leaf (0) 0 human/CHMP4A GO:0061952 midbody abscission ARBA:ARBA00029210 KEEP_AS_NON_CORE leaf (0) 0 human/CHMP4A GO:0071985 multivesicular body sorting pathway ARBA:ARBA00033501 ACCEPT specific (1-20) 6 human/CHMP4A GO:0097352 autophagosome maturation ARBA:ARBA00033540 ACCEPT specific (1-20) 1 human/CHMP4A GO:1901673 regulation of mitotic spindle assembly ARBA:ARBA00033492 KEEP_AS_NON_CORE specific (1-20) 3 human/CHMP4A GO:1902774 late endosome to lysosome transport ARBA:ARBA00033593 ACCEPT specific (1-20) 1 human/CHMP4A GO:1904930 amphisome membrane ARBA:ARBA00033513 ACCEPT leaf (0) 0 human/CHMP4B GO:0000776 kinetochore ARBA:ARBA00027576 KEEP_AS_NON_CORE specific (1-20) 11 human/CHMP4B GO:0001778 plasma membrane repair ARBA:ARBA00033547 KEEP_AS_NON_CORE leaf (0) 0 human/CHMP4B GO:0005643 nuclear pore ARBA:ARBA00026270 KEEP_AS_NON_CORE specific (1-20) 9 human/CHMP4B GO:0005765 lysosomal membrane ARBA:ARBA00028563 ACCEPT specific (1-20) 12 human/CHMP4B GO:0005828 kinetochore microtubule ARBA:ARBA00033604 KEEP_AS_NON_CORE specific (1-20) 1 human/CHMP4B GO:0007080 mitotic metaphase chromosome alignment ARBA:ARBA00033550 KEEP_AS_NON_CORE specific (1-20) 7 human/CHMP4B GO:0031468 nuclear membrane reassembly ARBA:ARBA00033562 KEEP_AS_NON_CORE specific (1-20) 7 human/CHMP4B GO:0032585 multivesicular body membrane ARBA:ARBA00033600 ACCEPT specific (1-20) 1 human/CHMP4B GO:0036258 multivesicular body assembly ARBA:ARBA00027035 ACCEPT leaf (0) 0 human/CHMP4B GO:0039702 viral budding via host ESCRT complex ARBA:ARBA00028526 KEEP_AS_NON_CORE leaf (0) 0 human/CHMP4B GO:0042803 protein homodimerization activity ARBA:ARBA00027933 MODIFY leaf (0) 0 OTHER_TERM different term needed replacement term Homodimerization is less informative than CHMP4B/Snf7-family polymerization and membrane bending. human/CHMP4B GO:0043162 ubiquitin-dependent protein catabolic process via the multivesicular body sorting pathway ARBA:ARBA00033490 ACCEPT specific (1-20) 1 human/CHMP4B GO:0046761 viral budding from plasma membrane ARBA:ARBA00033532 KEEP_AS_NON_CORE leaf (0) 0 human/CHMP4B GO:0061952 midbody abscission ARBA:ARBA00029210 KEEP_AS_NON_CORE leaf (0) 0 human/CHMP4B GO:0071985 multivesicular body sorting pathway ARBA:ARBA00033501 ACCEPT specific (1-20) 6 human/CHMP4B GO:0097352 autophagosome maturation ARBA:ARBA00033540 ACCEPT specific (1-20) 1 human/CHMP4B GO:1901673 regulation of mitotic spindle assembly ARBA:ARBA00033492 KEEP_AS_NON_CORE specific (1-20) 3 human/CHMP4B GO:1902774 late endosome to lysosome transport ARBA:ARBA00033593 ACCEPT specific (1-20) 1 human/CHMP4B GO:1904930 amphisome membrane ARBA:ARBA00033513 ACCEPT leaf (0) 0 human/CHMP4C GO:0000776 kinetochore ARBA:ARBA00027576 KEEP_AS_NON_CORE specific (1-20) 11 human/CHMP4C GO:0001778 plasma membrane repair ARBA:ARBA00033547 KEEP_AS_NON_CORE leaf (0) 0 human/CHMP4C GO:0005643 nuclear pore ARBA:ARBA00026270 KEEP_AS_NON_CORE specific (1-20) 9 human/CHMP4C GO:0005765 lysosomal membrane ARBA:ARBA00028563 KEEP_AS_NON_CORE specific (1-20) 12 human/CHMP4C GO:0005828 kinetochore microtubule ARBA:ARBA00033604 KEEP_AS_NON_CORE specific (1-20) 1 human/CHMP4C GO:0007080 mitotic metaphase chromosome alignment ARBA:ARBA00033550 KEEP_AS_NON_CORE specific (1-20) 7 human/CHMP4C GO:0030496 midbody ARBA:ARBA00033509 ACCEPT specific (1-20) 1 human/CHMP4C GO:0031468 nuclear membrane reassembly ARBA:ARBA00033562 KEEP_AS_NON_CORE specific (1-20) 7 human/CHMP4C GO:0032585 multivesicular body membrane ARBA:ARBA00033600 KEEP_AS_NON_CORE specific (1-20) 1 human/CHMP4C GO:0036258 multivesicular body assembly ARBA:ARBA00027035 KEEP_AS_NON_CORE leaf (0) 0 human/CHMP4C GO:0039702 viral budding via host ESCRT complex ARBA:ARBA00028526 MARK_AS_OVER_ANNOTATED leaf (0) 0 WRONG_PARALOG wrong paralog CHMP4C can bind ESCRT/ALIX machinery, but a direct CHMP4 paralog comparison found that CHMP4A or CHMP4C depletion did not inhibit HIV-1 release whereas CHMP4B depletion did; viral budding should not be treated as a CHMP4C core role. human/CHMP4C GO:0042803 protein homodimerization activity ARBA:ARBA00027933 MARK_AS_OVER_ANNOTATED leaf (0) 0 TOO_GENERAL true but uninformative generic The interaction evidence is real in some cases, but generic binding or homodimerization does not capture the informative CHMP4C function: ESCRT-III abscission-checkpoint regulation through Aurora B/CPC/ANCHR/VPS4-associated assemblies. human/CHMP4C GO:0043162 ubiquitin-dependent protein catabolic process via the multivesicular body sorting pathway ARBA:ARBA00033490 KEEP_AS_NON_CORE specific (1-20) 1 human/CHMP4C GO:0046761 viral budding from plasma membrane ARBA:ARBA00033532 MARK_AS_OVER_ANNOTATED leaf (0) 0 WRONG_PARALOG wrong paralog CHMP4C can bind ESCRT/ALIX machinery, but a direct CHMP4 paralog comparison found that CHMP4A or CHMP4C depletion did not inhibit HIV-1 release whereas CHMP4B depletion did; viral budding should not be treated as a CHMP4C core role. human/CHMP4C GO:0061952 midbody abscission ARBA:ARBA00029210 ACCEPT leaf (0) 0 human/CHMP4C GO:0071985 multivesicular body sorting pathway ARBA:ARBA00033501 KEEP_AS_NON_CORE specific (1-20) 6 human/CHMP4C GO:0097352 autophagosome maturation ARBA:ARBA00033540 KEEP_AS_NON_CORE specific (1-20) 1 human/CHMP4C GO:1901673 regulation of mitotic spindle assembly ARBA:ARBA00033492 KEEP_AS_NON_CORE specific (1-20) 3 human/CHMP4C GO:1902774 late endosome to lysosome transport ARBA:ARBA00033593 KEEP_AS_NON_CORE specific (1-20) 1 human/CHMP4C GO:1904930 amphisome membrane ARBA:ARBA00033513 KEEP_AS_NON_CORE leaf (0) 0 human/CHMP5 GO:0000776 kinetochore ARBA:ARBA00027576 KEEP_AS_NON_CORE specific (1-20) 11 human/CHMP5 GO:0001778 plasma membrane repair ARBA:ARBA00033547 KEEP_AS_NON_CORE leaf (0) 0 human/CHMP5 GO:0005643 nuclear pore ARBA:ARBA00026270 KEEP_AS_NON_CORE specific (1-20) 9 human/CHMP5 GO:0005765 lysosomal membrane ARBA:ARBA00028563 KEEP_AS_NON_CORE specific (1-20) 12 human/CHMP5 GO:0005828 kinetochore microtubule ARBA:ARBA00033604 KEEP_AS_NON_CORE specific (1-20) 1 human/CHMP5 GO:0007080 mitotic metaphase chromosome alignment ARBA:ARBA00033550 KEEP_AS_NON_CORE specific (1-20) 7 human/CHMP5 GO:0031468 nuclear membrane reassembly ARBA:ARBA00033562 KEEP_AS_NON_CORE specific (1-20) 7 human/CHMP5 GO:0032585 multivesicular body membrane ARBA:ARBA00033600 ACCEPT specific (1-20) 1 human/CHMP5 GO:0039702 viral budding via host ESCRT complex ARBA:ARBA00028526 MARK_AS_OVER_ANNOTATED leaf (0) 0 UNCLASSIFIED unclassified The key CHMP5/LIP5 study found CHMP5 depletion increased infectious HIV-1 release and concluded that only LIP5 is required for HIV release, so viral-budding annotations should not be treated as CHMP5 core function. human/CHMP5 GO:0043162 ubiquitin-dependent protein catabolic process via the multivesicular body sorting pathway ARBA:ARBA00033490 ACCEPT specific (1-20) 1 human/CHMP5 GO:0046761 viral budding from plasma membrane ARBA:ARBA00033532 MARK_AS_OVER_ANNOTATED leaf (0) 0 UNCLASSIFIED unclassified The key CHMP5/LIP5 study found CHMP5 depletion increased infectious HIV-1 release and concluded that only LIP5 is required for HIV release, so viral-budding annotations should not be treated as CHMP5 core function. human/CHMP5 GO:0061952 midbody abscission ARBA:ARBA00029210 KEEP_AS_NON_CORE leaf (0) 0 human/CHMP5 GO:0071985 multivesicular body sorting pathway ARBA:ARBA00033501 ACCEPT specific (1-20) 6 human/CHMP5 GO:0097352 autophagosome maturation ARBA:ARBA00033540 KEEP_AS_NON_CORE specific (1-20) 1 human/CHMP5 GO:1901673 regulation of mitotic spindle assembly ARBA:ARBA00033492 KEEP_AS_NON_CORE specific (1-20) 3 human/CHMP5 GO:1902774 late endosome to lysosome transport ARBA:ARBA00033593 ACCEPT specific (1-20) 1 human/CHMP5 GO:1904930 amphisome membrane ARBA:ARBA00033513 KEEP_AS_NON_CORE leaf (0) 0 human/CHMP6 GO:0000776 kinetochore ARBA:ARBA00027576 KEEP_AS_NON_CORE specific (1-20) 11 human/CHMP6 GO:0001778 plasma membrane repair ARBA:ARBA00033547 KEEP_AS_NON_CORE leaf (0) 0 human/CHMP6 GO:0005643 nuclear pore ARBA:ARBA00026270 KEEP_AS_NON_CORE specific (1-20) 9 human/CHMP6 GO:0005765 lysosomal membrane ARBA:ARBA00028563 KEEP_AS_NON_CORE specific (1-20) 12 human/CHMP6 GO:0005828 kinetochore microtubule ARBA:ARBA00033604 KEEP_AS_NON_CORE specific (1-20) 1 human/CHMP6 GO:0007080 mitotic metaphase chromosome alignment ARBA:ARBA00033550 KEEP_AS_NON_CORE specific (1-20) 7 human/CHMP6 GO:0030496 midbody ARBA:ARBA00033509 KEEP_AS_NON_CORE specific (1-20) 1 human/CHMP6 GO:0031468 nuclear membrane reassembly ARBA:ARBA00033562 KEEP_AS_NON_CORE specific (1-20) 7 human/CHMP6 GO:0032585 multivesicular body membrane ARBA:ARBA00033600 ACCEPT specific (1-20) 1 human/CHMP6 GO:0039702 viral budding via host ESCRT complex ARBA:ARBA00028526 MARK_AS_OVER_ANNOTATED leaf (0) 0 UNCLASSIFIED unclassified Viral budding is an ESCRT pathway output, but CHMP6-specific depletion did not reduce HIV-1 release/infectivity and CHMP6 overexpression was not inhibitory in a key viral budding assay. human/CHMP6 GO:0043162 ubiquitin-dependent protein catabolic process via the multivesicular body sorting pathway ARBA:ARBA00033490 ACCEPT specific (1-20) 1 human/CHMP6 GO:0046761 viral budding from plasma membrane ARBA:ARBA00033532 MARK_AS_OVER_ANNOTATED leaf (0) 0 UNCLASSIFIED unclassified Viral budding is an ESCRT pathway output, but CHMP6-specific depletion did not reduce HIV-1 release/infectivity and CHMP6 overexpression was not inhibitory in a key viral budding assay. human/CHMP6 GO:0061952 midbody abscission ARBA:ARBA00029210 KEEP_AS_NON_CORE leaf (0) 0 human/CHMP6 GO:0071985 multivesicular body sorting pathway ARBA:ARBA00033501 ACCEPT specific (1-20) 6 human/CHMP6 GO:0097352 autophagosome maturation ARBA:ARBA00033540 KEEP_AS_NON_CORE specific (1-20) 1 human/CHMP6 GO:1901673 regulation of mitotic spindle assembly ARBA:ARBA00033492 KEEP_AS_NON_CORE specific (1-20) 3 human/CHMP6 GO:1902774 late endosome to lysosome transport ARBA:ARBA00033593 ACCEPT specific (1-20) 1 human/CHMP6 GO:1904930 amphisome membrane ARBA:ARBA00033513 KEEP_AS_NON_CORE leaf (0) 0 human/CHMP7 GO:0000776 kinetochore ARBA:ARBA00027576 KEEP_AS_NON_CORE specific (1-20) 11 human/CHMP7 GO:0001778 plasma membrane repair ARBA:ARBA00033547 KEEP_AS_NON_CORE leaf (0) 0 human/CHMP7 GO:0005643 nuclear pore ARBA:ARBA00026270 MODIFY specific (1-20) 9 TOO_SPECIFIC overreach replacement term CHMP7 localizes to reforming nuclear-envelope/chromatin-disk sites; nuclear envelope is the more accurate cellular-component term. human/CHMP7 GO:0005765 lysosomal membrane ARBA:ARBA00028563 KEEP_AS_NON_CORE specific (1-20) 12 human/CHMP7 GO:0005828 kinetochore microtubule ARBA:ARBA00033604 KEEP_AS_NON_CORE specific (1-20) 1 human/CHMP7 GO:0007080 mitotic metaphase chromosome alignment ARBA:ARBA00033550 KEEP_AS_NON_CORE specific (1-20) 7 human/CHMP7 GO:0030496 midbody ARBA:ARBA00033509 KEEP_AS_NON_CORE specific (1-20) 1 human/CHMP7 GO:0031468 nuclear membrane reassembly ARBA:ARBA00033562 ACCEPT specific (1-20) 7 human/CHMP7 GO:0032585 multivesicular body membrane ARBA:ARBA00033600 KEEP_AS_NON_CORE specific (1-20) 1 human/CHMP7 GO:0039702 viral budding via host ESCRT complex ARBA:ARBA00028526 MARK_AS_OVER_ANNOTATED leaf (0) 0 UNCLASSIFIED unclassified The CHMP7 viral evidence is a dominant-negative overexpression effect on virus-like particle release, not an endogenous core CHMP7 viral-budding function. human/CHMP7 GO:0043162 ubiquitin-dependent protein catabolic process via the multivesicular body sorting pathway ARBA:ARBA00033490 KEEP_AS_NON_CORE specific (1-20) 1 human/CHMP7 GO:0046761 viral budding from plasma membrane ARBA:ARBA00033532 MARK_AS_OVER_ANNOTATED leaf (0) 0 UNCLASSIFIED unclassified The CHMP7 viral evidence is a dominant-negative overexpression effect on virus-like particle release, not an endogenous core CHMP7 viral-budding function. human/CHMP7 GO:0061952 midbody abscission ARBA:ARBA00029210 KEEP_AS_NON_CORE leaf (0) 0 human/CHMP7 GO:0071985 multivesicular body sorting pathway ARBA:ARBA00033501 KEEP_AS_NON_CORE specific (1-20) 6 human/CHMP7 GO:0097352 autophagosome maturation ARBA:ARBA00033540 KEEP_AS_NON_CORE specific (1-20) 1 human/CHMP7 GO:1901673 regulation of mitotic spindle assembly ARBA:ARBA00033492 MODIFY specific (1-20) 3 OTHER_TERM different term needed replacement term CHMP7 contributes specifically to nuclear membrane reassembly and NE sealing during mitotic exit rather than to broad mitotic progression or spindle assembly. human/CHMP7 GO:1902774 late endosome to lysosome transport ARBA:ARBA00033593 KEEP_AS_NON_CORE specific (1-20) 1 human/CHMP7 GO:1904930 amphisome membrane ARBA:ARBA00033513 KEEP_AS_NON_CORE leaf (0) 0 human/CHPT1 GO:0005737 cytoplasm ARBA:ARBA00026971 REMOVE very general (>200 descendants) 1146 WRONG_LOCATION wrong manual WRONG_LOCATION An ARBA electronic default that is incorrect for CHPT1. CHPT1 is a multi-pass integral membrane protein of the Golgi (10 TM helices; UniProt), not a soluble cytoplasmic protein. This bulk-cytoplasm call is a clearly-wrong IEA superseded by the experimental Golgi-membrane localization; remove. human/CHPT1 GO:0012505 endomembrane system ARBA:ARBA00028953 MARK_AS_OVER_ANNOTATED very general (>200 descendants) 357 TOO_GENERAL true but uninformative general Very general ARBA location. Consistent with Golgi/ER membrane residence but far less informative than the specific Golgi membrane annotation; over-annotated. human/CHRNA1 GO:0007154 cell communication ARBA:ARBA00028945 MODIFY very general (>200 descendants) 1207 NEEDS_MORE_SPECIFIC true but uninformative replacement term ARBA00028945 supplies the broad cell-communication inference. Human endplate physiology in PMID:9221765 identifies its target-specific scope: the muscle receptor converts motor-neuron acetylcholine into postsynaptic conductance. GO:0007274 captures this neuromuscular transmission step. Historical rule execution was not reconstructed. human/CHRNA1 GO:0023052 signaling ARBA:ARBA00026303 MODIFY very general (>200 descendants) 1141 NEEDS_MORE_SPECIFIC true but uninformative replacement term ARBA00026303 supplies the broad signaling inference. The performed target step is acetylcholine-triggered conductance at the muscle endplate, documented in PMID:9221765; GO:0007274 specifies that neuromuscular transmission role. The historical rule execution was not reconstructed. human/CHRNA1 GO:0042391 regulation of membrane potential ARBA:ARBA00028934 MODIFY general (21-200) 154 NEEDS_MORE_SPECIFIC true but uninformative replacement term ARBA00028934 supplies a broad membrane-potential inference. Independent human endplate measurements in PMID:9221765 and PMID:8872460 locate the demonstrated electrical effect on the postsynaptic muscle membrane, supporting the existing child term GO:0060078. This target-supported refinement does not reconstruct the historical rule execution or change its source fields. human/CHRNA4 GO:0095500 acetylcholine receptor signaling pathway ARBA:ARBA00027667 ACCEPT specific (1-20) 4 human/CHRNB1 GO:0007165 signal transduction ARBA:ARBA00029050 MODIFY very general (>200 descendants) 937 NEEDS_MORE_SPECIFIC true but uninformative replacement term ACh-evoked current in human beta1-containing receptors (PMID:27375219) identifies acetylcholine receptor signaling, GO:0095500, more precisely than unrestricted signal transduction. The ARBA source is retained; no presynaptic release mechanism is inferred. human/CHRNB1 GO:0007268 chemical synaptic transmission ARBA:ARBA00028185 ACCEPT general (21-200) 69 human/CHRNB1 GO:0050877 nervous system process ARBA:ARBA00029146 KEEP_AS_NON_CORE general (21-200) 194 human/CHRNB1 GO:1904315 transmitter-gated monoatomic ion channel activity involved in regulation of postsynaptic membrane potential ARBA:ARBA00027327 MODIFY specific (1-20) 1 NEEDS_MORE_SPECIFIC true but uninformative replacement term GO:0022848 is a typed descendant of GO:1904315 and adds acetylcholine and cation specificity while retaining the postsynaptic-potential role. Human beta1 reconstitution independently corroborates the channel contribution. human/CHRNB2 GO:0005892 acetylcholine-gated channel complex ARBA:ARBA00033574 ACCEPT leaf (0) 0 human/CHRNB2 GO:0015464 acetylcholine receptor activity ARBA:ARBA00087698 MODIFY specific (1-20) 1 OTHER_TERM different term needed replacement term Human β2 participates in the pore and complementary agonist-binding surface of assembled nicotinic receptors. The specific channel term is more informative than the original broad receptor/channel class. This describes the subunit contribution, not an autonomous β2 channel. human/CHRNB2 GO:0035094 response to nicotine ARBA:ARBA00089505 KEEP_AS_NON_CORE specific (1-20) 2 human/CHRNB2 GO:0042734 presynaptic membrane ARBA:ARBA00088391 ACCEPT specific (1-20) 6 human/CHRNB2 GO:0095500 acetylcholine receptor signaling pathway ARBA:ARBA00027667 ACCEPT specific (1-20) 4 human/CHRNG GO:0006936 muscle contraction ARBA:ARBA00043367 MODIFY general (21-200) 53 NEEDS_MORE_SPECIFIC true but uninformative replacement term PMID:16527851 reconstitutes wild-type human alpha1/beta1/gamma/delta receptors in rat GH4C1 cells and independently measures fetal receptor current in primary human myotubes. Gamma is a component of the conducting heteropentamer, not an autonomous channel. The performed role is receptor excitation that triggers skeletal-muscle contraction. The ARBA source is preserved, while independently measured target-containing receptor activity supplies the biological precision. human/CHRNG GO:0007154 cell communication ARBA:ARBA00028945 MODIFY very general (>200 descendants) 1207 NEEDS_MORE_SPECIFIC true but uninformative replacement term PMID:16527851 reconstitutes wild-type human alpha1/beta1/gamma/delta receptors in rat GH4C1 cells and independently measures fetal receptor current in primary human myotubes. Gamma is a component of the conducting heteropentamer, not an autonomous channel. Acetylcholine-triggered gating and postsynaptic cation flow define GO:0095500 more precisely than unrestricted communication/signaling; this is the receptor's own performed signaling step. human/CHRNG GO:0015267 channel activity ARBA:ARBA00028041 MODIFY general (21-200) 171 NEEDS_MORE_SPECIFIC true but uninformative replacement term Official InterPro/rule source identity is retained, with direct target-containing receptor experiments providing specificity. PMID:16527851 reconstitutes wild-type human alpha1/beta1/gamma/delta receptors in rat GH4C1 cells and independently measures fetal receptor current in primary human myotubes. Gamma is a component of the conducting heteropentamer, not an autonomous channel. GO:0022848 states the ligand and cation-selective channel mechanism; the official GO:0015464 usage comment directs ionotropic nicotinic receptors to this term. Historical enables/contributes_to qualifiers are preserved exactly; the core uses contributes_to for the subunit. human/CHRNG GO:0023052 signaling ARBA:ARBA00026303 MODIFY very general (>200 descendants) 1141 NEEDS_MORE_SPECIFIC true but uninformative replacement term PMID:16527851 reconstitutes wild-type human alpha1/beta1/gamma/delta receptors in rat GH4C1 cells and independently measures fetal receptor current in primary human myotubes. Gamma is a component of the conducting heteropentamer, not an autonomous channel. Acetylcholine-triggered gating and postsynaptic cation flow define GO:0095500 more precisely than unrestricted communication/signaling; this is the receptor's own performed signaling step. human/CHST14 GO:0005794 Golgi apparatus ARBA:ARBA00028708 ACCEPT general (21-200) 48 human/CHST6 GO:0001517 N-acetylglucosamine 6-O-sulfotransferase activity ARBA:ARBA00090127 ACCEPT leaf (0) 0 human/CHST6 GO:0006044 obsolete N-acetylglucosamine metabolic process ARBA:ARBA00084676 MODIFY specific (1-20) 2 OTHER_TERM different term needed replacement term The obsolete ARBA grouping term has no official replacement; its original identifier is preserved. Independent human enzyme and pathway-reconstitution experiments establish CHST6 as the catalyst of GlcNAc-6 sulfation in keratan synthesis. GO:0018146 is an evidence-based reviewer recommendation, not an automatic ontology replacement or a rewritten original donor/source assertion. human/CHST6 GO:0006790 sulfur compound metabolic process ARBA:ARBA00028021 MODIFY general (21-200) 190 OTHER_TERM different term needed replacement term The electronic sulfur-metabolism assertion is chemically correct but broadly scoped. Independent human enzyme and pathway-reconstitution experiments establish CHST6 as the catalyst of GlcNAc-6 sulfation in keratan synthesis. GO:0018146 is an evidence-based reviewer recommendation, not an automatic ontology replacement or a rewritten original donor/source assertion. human/CHST6 GO:0009101 glycoprotein biosynthetic process ARBA:ARBA00027560 MODIFY general (21-200) 37 NEEDS_MORE_SPECIFIC true but uninformative replacement term Glycoprotein biosynthesis is a correct broad context, but the enzyme performs a specific sulfation step. Independent human enzyme and pathway-reconstitution experiments establish CHST6 as the catalyst of GlcNAc-6 sulfation in keratan synthesis. GO:0018146 is an evidence-based reviewer recommendation, not an automatic ontology replacement or a rewritten original donor/source assertion. human/CHSY1 GO:0050650 chondroitin sulfate proteoglycan biosynthetic process ARBA:ARBA00034383 ACCEPT specific (1-20) 1 human/CIB2 GO:0000287 magnesium ion binding ARBA:ARBA00028486 ACCEPT leaf (0) 0 human/CIITA GO:0034341 response to type II interferon ARBA:ARBA00033603 ACCEPT specific (1-20) 3 human/CIITA GO:0045892 negative regulation of DNA-templated transcription ARBA:ARBA00029084 KEEP_AS_NON_CORE general (21-200) 39 human/CIITA GO:0045944 positive regulation of transcription by RNA polymerase II ARBA:ARBA00027996 ACCEPT specific (1-20) 12 human/CIRBP GO:0009409 response to cold ARBA:ARBA00028088 ACCEPT specific (1-20) 5 human/CISD2 GO:0005737 cytoplasm ARBA:ARBA00026971 ACCEPT very general (>200 descendants) 1146 human/CLCN4 GO:0005254 chloride channel activity ARBA:ARBA00026476 MODIFY specific (1-20) 12 OTHER_TERM different term needed replacement term Current target InterPro/FunFam and taxon conditions match ARBA00026476 condition sets 1 and 9, using zero-based numbering. That verified route emits a channel term; direct CLCN4 chloride/proton exchange supports the more accurate antiporter term. human/CLCN5 GO:0005254 chloride channel activity ARBA:ARBA00026476 MODIFY specific (1-20) 12 OTHER_TERM different term needed replacement term Current target InterPro/FunFam and taxon conditions match ARBA00026476 condition sets 1 and 9, using zero-based indices. The propagation route is therefore resolved; direct ClC-5 proton transport supplies the substrate-specific antiporter interpretation. human/CLCN5 GO:0005737 cytoplasm ARBA:ARBA00026971 KEEP_AS_NON_CORE very general (>200 descendants) 1146 human/CLCN5 GO:0012505 endomembrane system ARBA:ARBA00028953 MODIFY very general (>200 descendants) 357 NEEDS_MORE_SPECIFIC true but uninformative replacement term Direct human ClC-5 localization establishes an endosomal membrane pool. The current ARBA conditions do not reproduce the historical target match, but that route uncertainty is separate from the experimentally supported compartment refinement. human/CLCN7 GO:0005254 chloride channel activity ARBA:ARBA00026476 MODIFY specific (1-20) 12 OTHER_TERM different term needed replacement term ClC-7 mediates coupled 2Cl(-)/1H(+) exchange rather than passive channel conduction; chloride:proton antiporter activity (GO:0062158) is the accurate replacement. human/CLDN16 GO:0070160 tight junction ARBA:ARBA00027156 ACCEPT specific (1-20) 6 human/CLN3 GO:0006865 amino acid transport ARBA:ARBA00027044 KEEP_AS_NON_CORE very general (>200 descendants) 245 human/CLN3 GO:0006897 endocytosis ARBA:ARBA00027119 KEEP_AS_NON_CORE general (21-200) 64 human/CLN3 GO:0016192 vesicle-mediated transport ARBA:ARBA00028249 ACCEPT very general (>200 descendants) 232 human/CLN3 GO:0030003 intracellular monoatomic cation homeostasis ARBA:ARBA00028070 KEEP_AS_NON_CORE general (21-200) 75 human/CLN3 GO:0030162 regulation of proteolysis ARBA:ARBA00027404 KEEP_AS_NON_CORE general (21-200) 38 human/CLN3 GO:0061024 membrane organization ARBA:ARBA00028824 KEEP_AS_NON_CORE very general (>200 descendants) 283 human/CLRN1 GO:0007605 sensory perception of sound ARBA:ARBA00033578 ACCEPT specific (1-20) 2 human/CLRN1 GO:0007605 sensory perception of sound ARBA:ARBA00033578 ACCEPT specific (1-20) 2 human/CLTC GO:0005802 trans-Golgi network ARBA:ARBA00029112 ACCEPT specific (1-20) 3 human/CLTC GO:0006898 receptor-mediated endocytosis ARBA:ARBA00044584 ACCEPT general (21-200) 30 human/CLTC GO:0030136 clathrin-coated vesicle ARBA:ARBA00027482 ACCEPT general (21-200) 33 human/CLTC GO:0042147 retrograde transport, endosome to Golgi ARBA:ARBA00085977 ACCEPT specific (1-20) 3 human/CLYBL GO:0106064 regulation of cobalamin catabolic process ARBA:ARBA00091618 ACCEPT specific (1-20) 2 human/CNGB1 GO:0030553 cGMP binding ARBA:ARBA00045036 ACCEPT leaf (0) 0 human/CNGB3 GO:0005222 intracellularly cAMP-activated cation channel activity ARBA:ARBA00085528 KEEP_AS_NON_CORE leaf (0) 0 human/CNGB3 GO:0007601 visual perception ARBA:ARBA00086021 ACCEPT specific (1-20) 1 human/CNGB3 GO:0030553 cGMP binding ARBA:ARBA00045036 ACCEPT leaf (0) 0 human/CNOT3 GO:0005829 cytosol ARBA:ARBA00029243 ACCEPT general (21-200) 73 human/CNOT4 GO:0005829 cytosol ARBA:ARBA00029243 ACCEPT general (21-200) 73 human/CNTNAP2 GO:0007417 central nervous system development ARBA:ARBA00026561 KEEP_AS_NON_CORE very general (>200 descendants) 464 human/COCH GO:0140144 non-collagenous component of basement membrane ARBA:ARBA00096893 UNDECIDED specific (1-20) 18 human/COL11A2 GO:0005576 extracellular region ARBA:ARBA00027128 ACCEPT very general (>200 descendants) 276 human/COL11A2 GO:0005788 endoplasmic reticulum lumen ARBA:ARBA00028691 KEEP_AS_NON_CORE specific (1-20) 9 human/COL11A2 GO:0007605 sensory perception of sound ARBA:ARBA00033578 KEEP_AS_NON_CORE specific (1-20) 2 human/COL11A2 GO:0030199 collagen fibril organization ARBA:ARBA00085945 ACCEPT leaf (0) 0 human/COL11A2 GO:0051216 cartilage development ARBA:ARBA00089273 KEEP_AS_NON_CORE general (21-200) 29 human/COL18A1 GO:0005788 endoplasmic reticulum lumen ARBA:ARBA00028691 KEEP_AS_NON_CORE specific (1-20) 9 human/COL18A1 GO:0009653 anatomical structure morphogenesis ARBA:ARBA00026583 KEEP_AS_NON_CORE very general (>200 descendants) 1501 human/COL18A1 GO:0030938 collagen type XVIII trimer ARBA:ARBA00098128 ACCEPT leaf (0) 0 human/COL18A1 GO:0042127 regulation of cell population proliferation ARBA:ARBA00027546 KEEP_AS_NON_CORE very general (>200 descendants) 258 human/COL18A1 GO:0071953 elastic fiber ARBA:ARBA00084594 KEEP_AS_NON_CORE specific (1-20) 3 human/COL18A1 GO:0160108 animal gross anatomical part developmental process ARBA:ARBA00098139 KEEP_AS_NON_CORE very general (>200 descendants) 3010 human/COL1A1 GO:0005583 fibrillar collagen trimer ARBA:ARBA00086943 MODIFY specific (1-20) 7 NEEDS_MORE_SPECIFIC true but uninformative replacement term ARBA captures the fibrillar-collagen class. Human chain-composition and assembly experiments establish type I, rather than an unspecified fibrillar trimer. No additional trimer annotation is proposed and no mature mechanics are inferred from the C-propeptide crystal alone. human/COL1A1 GO:0005788 endoplasmic reticulum lumen ARBA:ARBA00028691 KEEP_AS_NON_CORE specific (1-20) 9 human/COL1A1 GO:0048513 animal organ development ARBA:ARBA00029247 KEEP_AS_NON_CORE very general (>200 descendants) 1888 human/COL1A2 GO:0005788 endoplasmic reticulum lumen ARBA:ARBA00028691 KEEP_AS_NON_CORE specific (1-20) 9 human/COL1A2 GO:0030199 collagen fibril organization ARBA:ARBA00085945 ACCEPT leaf (0) 0 human/COL1A2 GO:0048513 animal organ development ARBA:ARBA00029247 KEEP_AS_NON_CORE very general (>200 descendants) 1888 human/COL1A2 GO:0140151 solid phase of interstitial matrix ARBA:ARBA00093806 ACCEPT general (21-200) 32 human/COL2A1 GO:0005583 fibrillar collagen trimer ARBA:ARBA00086943 MODIFY specific (1-20) 7 NEEDS_MORE_SPECIFIC true but uninformative replacement term The broad ARBA fibrillar-trimer assertion is correct. The alpha-1(II) chain is directly established as the repeated chain in type-II homotrimers; it also contributes the alpha-3 chain of type XI, retained separately. Refinement of this existing broad source does not add a redundant annotation. human/COL2A1 GO:0005788 endoplasmic reticulum lumen ARBA:ARBA00028691 KEEP_AS_NON_CORE specific (1-20) 9 human/COL2A1 GO:0048513 animal organ development ARBA:ARBA00029247 KEEP_AS_NON_CORE very general (>200 descendants) 1888 human/COL3A1 GO:0005583 fibrillar collagen trimer ARBA:ARBA00086943 ACCEPT specific (1-20) 7 human/COL3A1 GO:0005788 endoplasmic reticulum lumen ARBA:ARBA00028691 ACCEPT specific (1-20) 9 human/COL3A1 GO:0030199 collagen fibril organization ARBA:ARBA00085945 ACCEPT leaf (0) 0 human/COL3A1 GO:0048513 animal organ development ARBA:ARBA00029247 KEEP_AS_NON_CORE very general (>200 descendants) 1888 human/COL4A1 GO:0005788 endoplasmic reticulum lumen ARBA:ARBA00028691 KEEP_AS_NON_CORE specific (1-20) 9 human/COL4A3 GO:0005788 endoplasmic reticulum lumen ARBA:ARBA00028691 ACCEPT specific (1-20) 9 human/COL4A4 GO:0005788 endoplasmic reticulum lumen ARBA:ARBA00028691 KEEP_AS_NON_CORE specific (1-20) 9 human/COL4A5 GO:0005788 endoplasmic reticulum lumen ARBA:ARBA00028691 ACCEPT specific (1-20) 9 human/COL5A1 GO:0005592 collagen type XI trimer ARBA:ARBA00093711 MODIFY leaf (0) 0 TOO_SPECIFIC overreach replacement term The collagen V/XI family shares fibrillar assembly biology, but GO:0005592 currently specifies the alpha1(XI)/alpha2(XI)/alpha1(II) composition. The review PMID:20705069 groups V and XI as tissue-specific isoforms of one collagen type, including alpha1(V)-containing type V trimers. Independently, PMID:19103590 identifies alpha1(V) in bovine V/XI polymers and partially resolves alpha1(XI)/alpha1(V)/alpha3(XI) hybrids. GO:0005583 retains the supported fibrillar-trimer assertion without assigning the canonical XI chain composition. This corrects an existing electronic source assertion; it adds no NEW coverage beyond the separate type V trimer annotations. The exact hybrid composition remains explicit here and in the ontology question. human/COL5A1 GO:0005788 endoplasmic reticulum lumen ARBA:ARBA00028691 KEEP_AS_NON_CORE specific (1-20) 9 human/COL5A2 GO:0005583 fibrillar collagen trimer ARBA:ARBA00086943 MODIFY specific (1-20) 7 NEEDS_MORE_SPECIFIC true but uninformative replacement term The current ARBA00086943 rule includes the target collagen FunFam and Primates branch, supporting a fibrillar collagen class. Independent human variant evidence and the type-V composition in PMID:21421911 support the more precise alpha1(V)2-alpha2(V) complex. A type-V alpha1 homotrimer observed when alpha2 incorporation fails is not a COL5A2 homotrimer. human/COL5A2 GO:0005788 endoplasmic reticulum lumen ARBA:ARBA00028691 KEEP_AS_NON_CORE specific (1-20) 9 human/COL5A2 GO:0048513 animal organ development ARBA:ARBA00029247 KEEP_AS_NON_CORE very general (>200 descendants) 1888 human/COL6A1 GO:0001527 microfibril ARBA:ARBA00028288 ACCEPT leaf (0) 0 human/COL6A1 GO:0005589 collagen type VI trimer ARBA:ARBA00093710 ACCEPT leaf (0) 0 human/COL6A1 GO:0005783 endoplasmic reticulum ARBA:ARBA00028672 KEEP_AS_NON_CORE general (21-200) 100 human/COL6A1 GO:0009653 anatomical structure morphogenesis ARBA:ARBA00026583 KEEP_AS_NON_CORE very general (>200 descendants) 1501 human/COL6A1 GO:0009888 tissue development ARBA:ARBA00028065 KEEP_AS_NON_CORE very general (>200 descendants) 1023 human/COL6A1 GO:0030154 cell differentiation ARBA:ARBA00027429 UNDECIDED very general (>200 descendants) 1345 human/COL6A1 GO:0160108 animal gross anatomical part developmental process ARBA:ARBA00098139 KEEP_AS_NON_CORE very general (>200 descendants) 3010 human/COL6A2 GO:0001527 microfibril ARBA:ARBA00028288 ACCEPT leaf (0) 0 human/COL6A2 GO:0005589 collagen type VI trimer ARBA:ARBA00093710 ACCEPT leaf (0) 0 human/COL6A2 GO:0005886 plasma membrane ARBA:ARBA00027801 KEEP_AS_NON_CORE very general (>200 descendants) 415 human/COL6A3 GO:0005589 collagen type VI trimer ARBA:ARBA00093710 ACCEPT leaf (0) 0 human/COL7A1 GO:0005590 collagen type VII trimer ARBA:ARBA00098055 ACCEPT leaf (0) 0 human/COL7A1 GO:0005788 endoplasmic reticulum lumen ARBA:ARBA00028691 KEEP_AS_NON_CORE specific (1-20) 9 human/COL9A1 GO:0005788 endoplasmic reticulum lumen ARBA:ARBA00028691 KEEP_AS_NON_CORE specific (1-20) 9 human/COL9A1 GO:0009887 animal organ morphogenesis ARBA:ARBA00028067 UNDECIDED very general (>200 descendants) 585 human/COMP GO:0008201 heparin binding ARBA:ARBA00027326 KEEP_AS_NON_CORE leaf (0) 0 human/COMP GO:1990341 thrombospondin complex ARBA:ARBA00097011 ACCEPT leaf (0) 0 human/COPG1 GO:0005794 Golgi apparatus ARBA:ARBA00028708 ACCEPT general (21-200) 48 human/COPG1 GO:0030133 transport vesicle ARBA:ARBA00027487 ACCEPT general (21-200) 41 human/COPG1 GO:0031090 organelle membrane ARBA:ARBA00027624 ACCEPT very general (>200 descendants) 333 human/COPG2 GO:0005794 Golgi apparatus ARBA:ARBA00028708 ACCEPT general (21-200) 48 human/COPG2 GO:0030133 transport vesicle ARBA:ARBA00027487 ACCEPT general (21-200) 41 human/COPG2 GO:0098588 bounding membrane of organelle ARBA:ARBA00027281 ACCEPT very general (>200 descendants) 201 human/COPS2 GO:0032991 protein-containing complex ARBA:ARBA00028902 ACCEPT very general (>200 descendants) 2083 human/COQ6 GO:0004497 monooxygenase activity ARBA:ARBA00028788 KEEP_AS_NON_CORE very general (>200 descendants) 358 human/CORO1A GO:0030027 lamellipodium ARBA:ARBA00086222 ACCEPT specific (1-20) 3 human/CORO1A GO:0051129 negative regulation of cellular component organization ARBA:ARBA00026626 MODIFY very general (>200 descendants) 285 NEEDS_MORE_SPECIFIC true but uninformative replacement term The current ARBA rule correctly matches the target coronin FunFam/primate branch but emits an extremely broad organization term. The direct purified human-protein assay resolves the biologically supported subtype. This precision change is not a claim that the rule propagated a foreign catalytic function. human/COX10 GO:0004659 prenyltransferase activity ARBA:ARBA00027066 MODIFY general (21-200) 39 NEEDS_MORE_SPECIFIC true but uninformative replacement term Current ARBA00027066 branches 1 and 20 match the official InterPro/FunFam features and human taxonomic lineage. The broad reaction is sound, but GO:0008495 specifies the experimentally grounded heme substrate and heme O product. The replacement term is already annotated on COX10; this corrects the source-specific row and adds no NEW assertion. human/COX10 GO:0006784 heme A biosynthetic process ARBA:ARBA00087087 ACCEPT leaf (0) 0 human/COX10 GO:0017004 cytochrome complex assembly ARBA:ARBA00086146 MODIFY specific (1-20) 9 NEEDS_MORE_SPECIFIC true but uninformative replacement term Current ARBA00086146 branch 3 matches the exact target FunFam and chordate lineage. The relevant cytochrome complex is respiratory complex IV. Human COX10-deficient fibroblasts have altered complex IV subassembly patterns, supporting the existing broad assembly context. This does not establish a heme-insertase activity or make assembly a separate direct catalytic core function. The replacement term is already annotated on COX10; this corrects the source-specific row and adds no NEW assertion. human/COX18 GO:0051205 protein insertion into membrane ARBA:ARBA00028605 MODIFY specific (1-20) 14 NEEDS_MORE_SPECIFIC true but uninformative replacement term COX18 specifically inserts the MT-CO2 C-tail into the mitochondrial inner membrane from the matrix; the more specific GO:0032979 (protein insertion into mitochondrial inner membrane from matrix) better captures this. Modify to the specific term rather than the generic parent. human/COX4I1 GO:0005758 mitochondrial intermembrane space ARBA:ARBA00033592 ACCEPT specific (1-20) 1 human/COX4I2 GO:0005758 mitochondrial intermembrane space ARBA:ARBA00033592 ACCEPT specific (1-20) 1 human/COX7B GO:0016020 membrane ARBA:ARBA00028763 MARK_AS_OVER_ANNOTATED very general (>200 descendants) 895 TOO_GENERAL true but uninformative generic The generic 'membrane' term is uninformative given the precise, experimentally supported mitochondrial inner membrane localization (GO:0005743). Retained but flagged as over-general. human/CP GO:0016722 oxidoreductase activity, acting on metal ions ARBA:ARBA00027769 MODIFY specific (1-20) 14 NEEDS_MORE_SPECIFIC true but uninformative replacement term Current ARBA00027769 branch 7 matches the official CP FunFam signatures 2.60.40.420:FF:000009 and 2.60.40.420:FF:000015 together with the Primates taxon predicate. This supports the broad metal-ion oxidoreductase premise. Human enzyme and iron-homeostasis evidence identify ferroxidase activity as the specific principal function, so GO:0004322 is the replacement. human/CPAP GO:0007099 centriole replication ARBA:ARBA00092134 ACCEPT specific (1-20) 1 human/CPAP GO:1902117 positive regulation of organelle assembly ARBA:ARBA00088865 MODIFY specific (1-20) 18 NEEDS_MORE_SPECIFIC true but uninformative replacement term Current ARBA00088865 branch 4 exactly matches CPAP FunFam 2.60.450.20:FF:000001 and Metazoa. The actual human assembly data support positive regulation of centriole replication more specifically than generic organelle assembly. The same specific process is already represented by an experimental row; this source-preserving MODIFY is not an additional NEW annotation. human/CPS1 GO:0090407 organophosphate biosynthetic process ARBA:ARBA00029048 MODIFY very general (>200 descendants) 274 NEEDS_MORE_SPECIFIC true but uninformative replacement term The product carbamoyl phosphate is technically an organophosphate, so the term is not incorrect, but it is uninformatively broad. The specific process is better captured by GO:0070409 carbamoyl phosphate biosynthetic process, which is separately and experimentally annotated. human/CPT1A GO:0006853 carnitine shuttle ARBA:ARBA00086863 ACCEPT leaf (0) 0 human/CPT1C GO:0003824 catalytic activity ARBA:ARBA00027533 ACCEPT very general (>200 descendants) 6405 human/CPT2 GO:0015909 long-chain fatty acid transport ARBA:ARBA00088749 MODIFY specific (1-20) 10 NEEDS_MORE_SPECIFIC true but uninformative replacement term CPT2 is an acyltransferase, not a transporter. Its contribution to long-chain fatty acid uptake is indirect (completing the carnitine shuttle). The more accurate terms are the carnitine shuttle and fatty acid beta-oxidation processes it enables. human/CR1 GO:0001848 complement binding ARBA:ARBA00091660 ACCEPT specific (1-20) 8 human/CR1 GO:0004875 complement receptor activity ARBA:ARBA00087820 ACCEPT specific (1-20) 8 human/CR1 GO:0005886 plasma membrane ARBA:ARBA00027801 ACCEPT very general (>200 descendants) 415 human/CR1 GO:0006957 complement activation, alternative pathway ARBA:ARBA00086627 ACCEPT leaf (0) 0 human/CR1 GO:0030449 regulation of complement activation ARBA:ARBA00027989 ACCEPT specific (1-20) 14 human/CR1 GO:1903659 regulation of complement-dependent cytotoxicity ARBA:ARBA00089218 ACCEPT specific (1-20) 2 human/CRISPLD1 GO:0060325 face morphogenesis ARBA:ARBA00091405 MARK_AS_OVER_ANNOTATED leaf (0) 0 UNCLASSIFIED unclassified A craniofacial role is plausible but not established. The full paper reports only one marginally transmitted CRISPLD1 SNP, states that CRISPLD1 variation alone is not a significant etiologic contributor, and calls for functional validation. Machine propagation converts this weak, interaction-dependent association into a normal-development process assertion that is too strong for current evidence. human/CRLS1 GO:0046474 glycerophospholipid biosynthetic process ARBA:ARBA00028351 ACCEPT general (21-200) 23 human/CRY1 GO:0019902 phosphatase binding ARBA:ARBA00087319 REMOVE specific (1-20) 5 WRONG_PARALOG wrong manual WRONG_PARALOG The cited interaction involves hCRY2 rather than CRY1. human/CRY2 GO:0019902 phosphatase binding ARBA:ARBA00087319 ACCEPT specific (1-20) 5 human/CRYAA GO:0005198 structural molecule activity ARBA:ARBA00027476 MODIFY general (21-200) 50 NEEDS_MORE_SPECIFIC true but uninformative replacement term "While structural molecule activity is correct for CRYAA as a major structural lens protein, the more specific child term GO:0005212 ""structural constituent of eye lens"" is already annotated and is more informative. Modifying to the specific term for consistency with the IDA annotation review of the same GO term." human/CRYAB GO:0005198 structural molecule activity ARBA:ARBA00027476 MODIFY general (21-200) 50 NEEDS_MORE_SPECIFIC true but uninformative replacement term "Structural molecule activity is broader than needed for CRYAB. The lens structural role is captured more precisely by GO:0005212 ""structural constituent of eye lens"", while muscle/cytoskeletal contexts are better captured by cytoskeletal protein binding and localization annotations." human/CRYAB GO:0009892 negative regulation of metabolic process ARBA:ARBA00028100 MARK_AS_OVER_ANNOTATED very general (>200 descendants) 788 TOO_GENERAL true but uninformative broad This is an overly broad term that does not add useful information beyond what is captured by more specific annotations such as GO:0043066 negative regulation of apoptotic process and GO:0031333 negative regulation of protein-containing complex assembly. The ARBA prediction likely derives from the general chaperone/anti-apoptotic activities but is too unspecific. human/CSF1R GO:0002573 myeloid leukocyte differentiation ARBA:ARBA00088984 ACCEPT specific (1-20) 20 human/CSF1R GO:0006950 response to stress ARBA:ARBA00026300 MARK_AS_OVER_ANNOTATED very general (>200 descendants) 590 TOO_GENERAL true but uninformative general Response to stress is too general to be informative for a cytokine receptor; CSF1R is better described by M-CSF signaling, inflammatory response and myeloid differentiation terms already present. human/CSF1R GO:0008283 cell population proliferation ARBA:ARBA00035743 MODIFY general (21-200) 163 NEEDS_MORE_SPECIFIC true but uninformative replacement term CSF1R positively regulates proliferation of macrophages and their precursors; the regulatory term GO:0008284 positive regulation of cell population proliferation is more accurate than the generic parent. human/CSF1R GO:0009653 anatomical structure morphogenesis ARBA:ARBA00026583 MARK_AS_OVER_ANNOTATED very general (>200 descendants) 1501 INDIRECT_EFFECT overreach indirect Too general; CSF1R affects morphogenesis (bone, mammary ducts, brain) indirectly through macrophages/osteoclasts/microglia. More specific, better supported terms (osteoclast differentiation, macrophage differentiation) exist. human/CSF1R GO:0022604 regulation of cell morphogenesis ARBA:ARBA00091911 KEEP_AS_NON_CORE general (21-200) 62 human/CSF1R GO:0048513 animal organ development ARBA:ARBA00029247 MARK_AS_OVER_ANNOTATED very general (>200 descendants) 1888 INDIRECT_EFFECT overreach indirect Too general; developmental effects of CSF1R on bone, brain and mammary gland are indirect, through macrophages, osteoclasts and microglia. human/CSK GO:0005829 cytosol ARBA:ARBA00029243 ACCEPT general (21-200) 73 human/CSK GO:0050776 regulation of immune response ARBA:ARBA00028647 KEEP_AS_NON_CORE very general (>200 descendants) 505 human/CSK GO:0051239 regulation of multicellular organismal process ARBA:ARBA00028859 MARK_AS_OVER_ANNOTATED very general (>200 descendants) 1807 TOO_GENERAL true but uninformative broad Extremely broad, uninformative grouping term. human/CSNK1D GO:0030111 regulation of Wnt signaling pathway ARBA:ARBA00027324 ACCEPT specific (1-20) 20 human/CTLA4 GO:0009897 external side of plasma membrane ARBA:ARBA00043397 ACCEPT specific (1-20) 4 human/CTNNA1 GO:0008092 cytoskeletal protein binding ARBA:ARBA00029239 MODIFY general (21-200) 53 NEEDS_MORE_SPECIFIC true but uninformative replacement term Correct but general; the specific activity is actin filament binding. human/CTNNA1 GO:0098797 plasma membrane protein complex ARBA:ARBA00028841 ACCEPT very general (>200 descendants) 309 human/CTNNB1 GO:0045766 positive regulation of angiogenesis ARBA:ARBA00084376 KEEP_AS_NON_CORE specific (1-20) 3 human/CTNNB1 GO:0050982 detection of mechanical stimulus ARBA:ARBA00091369 MARK_AS_OVER_ANNOTATED specific (1-20) 10 NO_EVIDENCE overreach No evidence No evidence that beta-catenin itself is a mechanosensor; it transduces forces as part of the cadherin-catenin complex. human/CTNNB1 GO:0071664 catenin-TCF7L2 complex ARBA:ARBA00092110 ACCEPT specific (1-20) 2 human/CTNNB1 GO:0071681 cellular response to indole-3-methanol ARBA:ARBA00092149 MARK_AS_OVER_ANNOTATED leaf (0) 0 INDIRECT_EFFECT overreach raised catenin expression Indole-3-carbinol raised catenin expression in breast cancer cells; an expression change does not show that beta-catenin functions in a response to this compound. human/CUBN GO:0030139 endocytic vesicle ARBA:ARBA00027489 ACCEPT general (21-200) 35 human/CUBN GO:0031253 cell projection membrane ARBA:ARBA00086459 ACCEPT general (21-200) 25 human/CUL1 GO:0000082 G1/S transition of mitotic cell cycle ARBA:ARBA00028571 ACCEPT leaf (0) 0 human/CUL1 GO:0005829 cytosol ARBA:ARBA00029243 ACCEPT general (21-200) 73 human/CUL1 GO:0070936 protein K48-linked ubiquitination ARBA:ARBA00086253 ACCEPT leaf (0) 0 human/CUL1 GO:0097193 intrinsic apoptotic signaling pathway ARBA:ARBA00028303 MARK_AS_OVER_ANNOTATED specific (1-20) 13 INDIRECT_EFFECT overreach phenotype The worm phenotype (and the ARBA rule derived from it) reflects failed cell-cycle exit, not participation of CUL1 in the intrinsic apoptotic signaling cascade; over-annotation. human/CUL1 GO:0160072 ubiquitin ligase complex scaffold activity ARBA:ARBA00088321 ACCEPT leaf (0) 0 human/CUL3 GO:0000209 protein polyubiquitination ARBA:ARBA00044436 ACCEPT specific (1-20) 9 human/CUL3 GO:0000278 mitotic cell cycle ARBA:ARBA00028458 MARK_AS_OVER_ANNOTATED general (21-200) 121 INDIRECT_EFFECT overreach phenotype The Falcon synthesis warns against promoting broad pathway, development, disease, or phenotype terms to core CUL3 annotations without direct mechanistic evidence at the annotated pathway node. human/CUL3 GO:0006915 apoptotic process ARBA:ARBA00027755 MARK_AS_OVER_ANNOTATED general (21-200) 115 INDIRECT_EFFECT overreach phenotype The Falcon synthesis warns against promoting broad pathway, development, disease, or phenotype terms to core CUL3 annotations without direct mechanistic evidence at the annotated pathway node. human/CUL3 GO:0006950 response to stress ARBA:ARBA00026300 MARK_AS_OVER_ANNOTATED very general (>200 descendants) 590 INDIRECT_EFFECT overreach phenotype The Falcon synthesis warns against promoting broad pathway, development, disease, or phenotype terms to core CUL3 annotations without direct mechanistic evidence at the annotated pathway node. human/CUL3 GO:0007165 signal transduction ARBA:ARBA00029050 MARK_AS_OVER_ANNOTATED very general (>200 descendants) 937 INDIRECT_EFFECT overreach phenotype The Falcon synthesis warns against promoting broad pathway, development, disease, or phenotype terms to core CUL3 annotations without direct mechanistic evidence at the annotated pathway node. human/CUL3 GO:0010468 regulation of gene expression ARBA:ARBA00028334 MARK_AS_OVER_ANNOTATED very general (>200 descendants) 874 INDIRECT_EFFECT overreach phenotype The Falcon synthesis warns against promoting broad pathway, development, disease, or phenotype terms to core CUL3 annotations without direct mechanistic evidence at the annotated pathway node. human/CUL3 GO:0043161 proteasome-mediated ubiquitin-dependent protein catabolic process ARBA:ARBA00026940 ACCEPT specific (1-20) 13 human/CYB5D2 GO:0005496 steroid binding ARBA:ARBA00087127 ACCEPT general (21-200) 22 human/CYB5R4 GO:0016653 oxidoreductase activity, acting on NAD(P)H, heme protein as acceptor ARBA:ARBA00027025 ACCEPT specific (1-20) 6 human/CYC1 GO:0016020 membrane ARBA:ARBA00028763 MARK_AS_OVER_ANNOTATED very general (>200 descendants) 895 TOO_GENERAL true but uninformative more specific "Per project curation guidelines, when a more specific compartment term is supported, the generic ""membrane"" term should not be a primary annotation. Falcon and openai both consistently place CYC1 at the inner mitochondrial membrane." human/CYP11A1 GO:0005739 mitochondrion ARBA:ARBA00026962 KEEP_AS_NON_CORE general (21-200) 70 human/CYP11A1 GO:0006700 C21-steroid hormone biosynthetic process ARBA:ARBA00087621 ACCEPT specific (1-20) 2 human/CYP11A1 GO:0008395 steroid hydroxylase activity ARBA:ARBA00026772 MARK_AS_OVER_ANNOTATED general (21-200) 37 TOO_GENERAL true but uninformative broad Steroid hydroxylase activity is a broad parent capturing the two hydroxylation steps, but CYP11A1's diagnostic function includes the subsequent C-C bond cleavage and is fully captured by GO:0008386. Retaining this generic term as core would under-specify the function. human/CYP11A1 GO:0016125 sterol metabolic process ARBA:ARBA00034378 KEEP_AS_NON_CORE specific (1-20) 13 human/CYP11A1 GO:0016713 oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, reduced iron-sulfur protein as one donor, and incorporation of one atom of oxygen ARBA:ARBA00027740 MARK_AS_OVER_ANNOTATED specific (1-20) 20 TOO_GENERAL true but uninformative broad This term accurately describes the mitochondrial-P450 mechanism (electrons from the iron-sulfur protein adrenodoxin), but it is a broad functional parent subsumed by the specific cholesterol side-chain-cleaving activity; retain as over-annotated rather than core. human/CYP11B1 GO:0016125 sterol metabolic process ARBA:ARBA00034378 KEEP_AS_NON_CORE specific (1-20) 13 human/CYP11B1 GO:0032342 aldosterone biosynthetic process ARBA:ARBA00095220 MARK_AS_OVER_ANNOTATED leaf (0) 0 WRONG_PARALOG wrong this is the function of Same over-annotation as the IBA aldosterone term: human CYP11B1 lacks 18-oxidase activity and does not make aldosterone; this is the function of CYP11B2. human/CYP11B2 GO:0016125 sterol metabolic process ARBA:ARBA00034378 MARK_AS_OVER_ANNOTATED specific (1-20) 13 TOO_GENERAL true but uninformative broad Over-broad rule-based annotation inherited from steroidogenic P450 context; the enzyme's substrates are corticosteroids, not sterols per se. human/CYP11B2 GO:0032342 aldosterone biosynthetic process ARBA:ARBA00095220 ACCEPT leaf (0) 0 human/CYP17A1 GO:0008202 steroid metabolic process ARBA:ARBA00027309 KEEP_AS_NON_CORE general (21-200) 73 human/CYP17A1 GO:0008395 steroid hydroxylase activity ARBA:ARBA00026772 MARK_AS_OVER_ANNOTATED general (21-200) 37 TOO_GENERAL true but uninformative general Over-general parent of the specific, experimentally supported core MF GO:0004508. human/CYP17A1 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 ARBA:ARBA00027735 MARK_AS_OVER_ANNOTATED general (21-200) 128 TOO_GENERAL true but uninformative general Mechanistic ancestor term (reduced flavoprotein donor, one oxygen atom incorporated); over-general relative to the specific core MF GO:0004508. human/CYP17A1 GO:0034308 primary alcohol metabolic process ARBA:ARBA00029060 MARK_AS_OVER_ANNOTATED general (21-200) 64 UNCLASSIFIED unclassified Chemistry-derived over-annotation; not a biologically meaningful process term for this steroidogenic enzyme. The relevant BP is steroid hormone biosynthesis. human/CYP17A1 GO:0042445 hormone metabolic process ARBA:ARBA00028011 KEEP_AS_NON_CORE general (21-200) 85 human/CYP17A1 GO:0120254 olefinic compound metabolic process ARBA:ARBA00033535 MARK_AS_OVER_ANNOTATED general (21-200) 90 UNCLASSIFIED unclassified Chemistry-derived over-annotation with no biological specificity for this enzyme; the meaningful process is steroid hormone biosynthesis. human/CYP19A1 GO:0006703 estrogen biosynthetic process ARBA:ARBA00087624 ACCEPT leaf (0) 0 human/CYP19A1 GO:0008209 androgen metabolic process ARBA:ARBA00027345 KEEP_AS_NON_CORE specific (1-20) 2 human/CYP19A1 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 ARBA:ARBA00027735 MARK_AS_OVER_ANNOTATED general (21-200) 128 TOO_GENERAL true but uninformative parent Correct EC-level parent (P450 monooxygenase using flavoprotein/POR as donor) but over-general; the specific MF GO:0070330 is annotated with experimental evidence. human/CYP21A2 GO:0006705 mineralocorticoid biosynthetic process ARBA:ARBA00087623 ACCEPT specific (1-20) 1 human/CYP21A2 GO:0034308 primary alcohol metabolic process ARBA:ARBA00029060 MARK_AS_OVER_ANNOTATED general (21-200) 64 TOO_GENERAL true but uninformative already captured The product hydroxyl is a primary alcohol, but the biologically meaningful process is corticosteroid biosynthesis, already captured by the specific glucocorticoid/mineralocorticoid/cortisol terms. This substrate-chemistry parent adds no functional insight. human/CYP21A2 GO:0042180 ketone metabolic process ARBA:ARBA00027488 MARK_AS_OVER_ANNOTATED general (21-200) 128 TOO_GENERAL true but uninformative generic The steroid substrates carry ketone groups, but the biologically relevant process is corticosteroid biosynthesis; this generic parent adds no functional insight. human/CYP21A2 GO:0120254 olefinic compound metabolic process ARBA:ARBA00033535 MARK_AS_OVER_ANNOTATED general (21-200) 90 TOO_GENERAL true but uninformative parent The steroid substrates contain a carbon-carbon double bond, but CYP21A2's biological role is corticosteroid biosynthesis, not olefin metabolism; this parent adds no functional insight. human/CYP27A1 GO:0005739 mitochondrion ARBA:ARBA00026962 ACCEPT general (21-200) 70 human/CYP27A1 GO:0008202 steroid metabolic process ARBA:ARBA00027309 ACCEPT general (21-200) 73 human/CYP27A1 GO:0008610 lipid biosynthetic process ARBA:ARBA00027236 MARK_AS_OVER_ANNOTATED very general (>200 descendants) 258 TOO_GENERAL true but uninformative general Overly general; CYP27A1's biosynthetic contributions are specifically to bile acids and oxysterols, already captured by more precise terms. human/CYP39A1 GO:0007586 digestion ARBA:ARBA00086401 MARK_AS_OVER_ANNOTATED general (21-200) 32 INDIRECT_EFFECT overreach Downstream Downstream physiological consequence of bile-acid production, not this enzyme's function; the alternative pathway is a minor bile-acid source focused on cholesterol clearance. human/CYP39A1 GO:0008387 steroid 7-alpha-hydroxylase activity ARBA:ARBA00092070 MARK_AS_OVER_ANNOTATED specific (1-20) 4 TOO_GENERAL true but uninformative parent Accurate parent term but subsumed by GO:0033782; retained as a valid but over-general ancestor. human/CYP39A1 GO:0016125 sterol metabolic process ARBA:ARBA00034378 KEEP_AS_NON_CORE specific (1-20) 13 human/CYP7A1 GO:0008206 bile acid metabolic process ARBA:ARBA00092298 MARK_AS_OVER_ANNOTATED specific (1-20) 3 TOO_GENERAL true but uninformative redundant True but redundant with the more specific bile acid biosynthetic process annotation; retained as a correct general term. human/CYP7A1 GO:0016125 sterol metabolic process ARBA:ARBA00034378 MARK_AS_OVER_ANNOTATED specific (1-20) 13 UNCLASSIFIED unclassified Accurate at a high level but less informative than the specific process terms already present. human/CYP7B1 GO:0008202 steroid metabolic process ARBA:ARBA00027309 ACCEPT general (21-200) 73 human/CYP8B1 GO:0006629 lipid metabolic process ARBA:ARBA00028591 MARK_AS_OVER_ANNOTATED very general (>200 descendants) 608 TOO_GENERAL true but uninformative general Correct but very general (ARBA IEA). CYP8B1 acts in bile-acid biosynthesis, a specific branch of lipid metabolism; the specific term GO:0006699 is preferred. Over-annotation. human/CYP8B1 GO:0072330 monocarboxylic acid biosynthetic process ARBA:ARBA00027175 MARK_AS_OVER_ANNOTATED general (21-200) 95 TOO_GENERAL true but uninformative general Correct but general (ARBA IEA). Bile acids are monocarboxylic acids, so this is a true parent of bile acid biosynthetic process (GO:0006699). The specific term is preferred. Over-annotation. human/DBT GO:0016747 acyltransferase activity, transferring groups other than amino-acyl groups ARBA:ARBA00027717 MARK_AS_OVER_ANNOTATED very general (>200 descendants) 345 TOO_GENERAL true but uninformative general Correct but a general parent of the specific GO:0043754 activity that is already annotated. Retained as accurate but non-informative relative to the specific transacylase term. human/DBT GO:0120552 branched-chain alpha-keto acid decarboxylation to branched-chain acyl-CoA ARBA:ARBA00095351 ACCEPT leaf (0) 0 human/DCX GO:0007417 central nervous system development ARBA:ARBA00026561 KEEP_AS_NON_CORE very general (>200 descendants) 464 human/DDB1 GO:0034644 cellular response to UV ARBA:ARBA00026679 ACCEPT specific (1-20) 8 human/DDB2 GO:0034644 cellular response to UV ARBA:ARBA00026679 ACCEPT specific (1-20) 8 human/DDC GO:0042401 biogenic amine biosynthetic process ARBA:ARBA00028120 KEEP_AS_NON_CORE general (21-200) 21 human/DDOST GO:0016020 membrane ARBA:ARBA00028763 KEEP_AS_NON_CORE very general (>200 descendants) 895 human/DEGS1 GO:0003824 catalytic activity ARBA:ARBA00027533 MARK_AS_OVER_ANNOTATED very general (>200 descendants) 6405 TOO_GENERAL true but uninformative Uninformative Uninformative parent term subsumed by the specific sphingolipid delta-4 desaturase activity; retained only as an electronic generalization. human/DENR GO:0002183 cytoplasmic translational initiation ARBA:ARBA00087684 KEEP_AS_NON_CORE specific (1-20) 9 human/DFFA GO:0042981 regulation of apoptotic process ARBA:ARBA00027086 MODIFY very general (>200 descendants) 218 OTHER_TERM different term needed replacement term Regulation of apoptotic process is much broader than the direct DFFA role. The DFF45/ICAD mechanism is sequestration of CAD/DFF40 nuclease activity until caspase cleavage, best represented as negative regulation of apoptotic DNA fragmentation. human/DFFA GO:1902511 negative regulation of apoptotic DNA fragmentation ARBA:ARBA00092131 ACCEPT leaf (0) 0 human/DGUOK GO:1901135 carbohydrate derivative metabolic process ARBA:ARBA00026297 KEEP_AS_NON_CORE very general (>200 descendants) 637 human/DIABLO GO:0043065 positive regulation of apoptotic process ARBA:ARBA00027745 MODIFY general (21-200) 68 OTHER_TERM different term needed replacement term This ARBA row has the right pro-apoptotic direction, but DIABLO acts in the mitochondrial IAP-antagonist step and should be narrowed to intrinsic apoptotic signaling pathway. human/DIABLO GO:0097193 intrinsic apoptotic signaling pathway ARBA:ARBA00028303 ACCEPT specific (1-20) 13 human/DLL1 GO:0030154 cell differentiation ARBA:ARBA00027429 KEEP_AS_NON_CORE very general (>200 descendants) 1345 human/DLL1 GO:0048018 receptor ligand activity ARBA:ARBA00028558 ACCEPT general (21-200) 34 human/DNAJA2 GO:0001671 ATPase activator activity ARBA:ARBA00089918 ACCEPT specific (1-20) 1 human/DNAJA2 GO:0051087 protein-folding chaperone binding ARBA:ARBA00088077 ACCEPT specific (1-20) 1 human/DNAJA4 GO:0051087 protein-folding chaperone binding ARBA:ARBA00088077 ACCEPT specific (1-20) 1 human/DNAJB1 GO:0006986 response to unfolded protein ARBA:ARBA00086617 ACCEPT specific (1-20) 7 human/DNAJB1 GO:0051087 protein-folding chaperone binding ARBA:ARBA00088077 ACCEPT specific (1-20) 1 human/DNAJB13 GO:0007017 microtubule-based process ARBA:ARBA00026739 KEEP_AS_NON_CORE very general (>200 descendants) 206 human/DNAJB2 GO:0051087 protein-folding chaperone binding ARBA:ARBA00088077 ACCEPT specific (1-20) 1 human/DNAJB2 GO:0090084 negative regulation of inclusion body assembly ARBA:ARBA00087599 ACCEPT specific (1-20) 2 human/DNAJB4 GO:0006986 response to unfolded protein ARBA:ARBA00086617 KEEP_AS_NON_CORE specific (1-20) 7 human/DNAJB4 GO:0051087 protein-folding chaperone binding ARBA:ARBA00088077 ACCEPT specific (1-20) 1 human/DNAJB5 GO:0006986 response to unfolded protein ARBA:ARBA00086617 KEEP_AS_NON_CORE specific (1-20) 7 human/DNAJB5 GO:0051087 protein-folding chaperone binding ARBA:ARBA00088077 ACCEPT specific (1-20) 1 human/DNAJB8 GO:0005737 cytoplasm ARBA:ARBA00026971 ACCEPT very general (>200 descendants) 1146 human/DNAJB8 GO:0051087 protein-folding chaperone binding ARBA:ARBA00088077 ACCEPT specific (1-20) 1 human/DNAJB8 GO:0090084 negative regulation of inclusion body assembly ARBA:ARBA00087599 ACCEPT specific (1-20) 2 human/DNAJC1 GO:0001671 ATPase activator activity ARBA:ARBA00089918 ACCEPT specific (1-20) 1 human/DNAJC1 GO:0051246 regulation of protein metabolic process ARBA:ARBA00028884 KEEP_AS_NON_CORE very general (>200 descendants) 442 human/DNAJC27 GO:0031410 cytoplasmic vesicle ARBA:ARBA00027190 MARK_AS_OVER_ANNOTATED very general (>200 descendants) 274 TOO_GENERAL true but uninformative Generic Generic Rab-family vesicle association predicted by a machine-learning rule; conflicts with the established nuclear localization and is unsupported by experimental data for this protein. human/DNAJC5 GO:0005737 cytoplasm ARBA:ARBA00026971 KEEP_AS_NON_CORE very general (>200 descendants) 1146 human/DNAJC5B GO:0005737 cytoplasm ARBA:ARBA00026971 KEEP_AS_NON_CORE very general (>200 descendants) 1146 human/DNAJC5G GO:0005737 cytoplasm ARBA:ARBA00026971 KEEP_AS_NON_CORE very general (>200 descendants) 1146 human/DNAJC6 GO:1905443 regulation of clathrin coat assembly ARBA:ARBA00087398 ACCEPT specific (1-20) 2 human/DNER GO:0007399 nervous system development ARBA:ARBA00027428 KEEP_AS_NON_CORE very general (>200 descendants) 913 human/DNER GO:0030425 dendrite ARBA:ARBA00028031 ACCEPT general (21-200) 37 human/DNM1L GO:0042802 identical protein binding ARBA:ARBA00027930 KEEP_AS_NON_CORE specific (1-20) 1 human/DNM1L GO:0043653 mitochondrial fragmentation involved in apoptotic process ARBA:ARBA00087404 ACCEPT leaf (0) 0 human/DNM1L GO:0048312 intracellular distribution of mitochondria ARBA:ARBA00089911 KEEP_AS_NON_CORE leaf (0) 0 human/DNM1L GO:0048471 perinuclear region of cytoplasm ARBA:ARBA00091589 KEEP_AS_NON_CORE specific (1-20) 7 human/DNM1L GO:0090141 positive regulation of mitochondrial fission ARBA:ARBA00087305 MODIFY leaf (0) 0 TOO_SPECIFIC overreach replacement term DNM1L is the fission effector itself rather than a regulator; the appropriate term is mitochondrial fission (already annotated many times). human/DNM1L GO:1903532 positive regulation of secretion by cell ARBA:ARBA00089016 MARK_AS_OVER_ANNOTATED general (21-200) 83 TOO_GENERAL true but uninformative General Generalization of a single early overexpression observation; not a recognized DNM1L function. human/DNMT3A GO:0003714 transcription corepressor activity ARBA:ARBA00089152 ACCEPT specific (1-20) 1 human/DPEP1 GO:1901749 leukotriene D4 catabolic process ARBA:ARBA00091118 ACCEPT leaf (0) 0 human/DPM1 GO:0006506 GPI anchor biosynthetic process ARBA:ARBA00026293 KEEP_AS_NON_CORE leaf (0) 0 human/DPM1 GO:0043048 dolichyl monophosphate biosynthetic process ARBA:ARBA00095221 ACCEPT leaf (0) 0 human/DPYD GO:0006208 pyrimidine nucleobase catabolic process ARBA:ARBA00086398 ACCEPT specific (1-20) 3 human/DTL GO:0006974 DNA damage response ARBA:ARBA00026271 ACCEPT general (21-200) 95 human/DTL GO:0045732 positive regulation of protein catabolic process ARBA:ARBA00026548 ACCEPT specific (1-20) 13 human/DUOX1 GO:0009615 response to virus ARBA:ARBA00026492 UNDECIDED specific (1-20) 9 human/DUOX1 GO:0031252 cell leading edge ARBA:ARBA00028924 UNDECIDED general (21-200) 22 human/DUOX1 GO:0051591 response to cAMP ARBA:ARBA00088700 UNDECIDED specific (1-20) 2 human/DUOX1 GO:0071345 cellular response to cytokine stimulus ARBA:ARBA00027915 UNDECIDED general (21-200) 149 human/DUOX1 GO:0090303 positive regulation of wound healing ARBA:ARBA00026837 KEEP_AS_NON_CORE specific (1-20) 9 human/DUSP6 GO:0043409 negative regulation of MAPK cascade ARBA:ARBA00027203 MODIFY specific (1-20) 9 NEEDS_MORE_SPECIFIC true but uninformative replacement term Correct in direction, but DUSP6 is selective for ERK1/2 and does not inhibit stress-activated JNK or p38 signalling in cells [PMID:8670865]; the more specific GO:0070373 negative regulation of ERK1 and ERK2 cascade is preferred. human/DUSP6 GO:0070371 ERK1 and ERK2 cascade ARBA:ARBA00085205 MODIFY leaf (0) 0 NEEDS_MORE_SPECIFIC true but uninformative replacement term DUSP6 does not propagate the ERK/MAPK signal; it terminates it by dephosphorylating activated ERK1/2 as a feedback inhibitor [PMID:18321244; PMID:18771677]. Membership of the pathway is better expressed by the regulatory term GO:0070373 negative regulation of ERK1 and ERK2 cascade. human/DUT GO:0009177 pyrimidine deoxyribonucleoside monophosphate biosynthetic process ARBA:ARBA00090968 MARK_AS_OVER_ANNOTATED specific (1-20) 5 TOO_GENERAL true but uninformative already annotated Not wrong (dUMP is a pyrimidine deoxyribonucleoside monophosphate), but this ARBA IEA is less precise than the dedicated GO:0006226 dUMP biosynthetic process term already annotated; the specific term better captures DUT's role. human/DUT GO:0009221 pyrimidine deoxyribonucleotide biosynthetic process ARBA:ARBA00090593 MARK_AS_OVER_ANNOTATED specific (1-20) 12 TOO_GENERAL true but uninformative broad Directionally correct as DUT feeds pyrimidine deoxyribonucleotide (dTMP/dTTP) biosynthesis by providing dUMP, but this is a broad parent term less precise than the specific dUMP biosynthetic process / dTMP biosynthetic process annotations already present. human/DYNC1H1 GO:0005868 cytoplasmic dynein complex ARBA:ARBA00088183 ACCEPT leaf (0) 0 human/DYNC2H1 GO:0005868 cytoplasmic dynein complex ARBA:ARBA00088183 ACCEPT leaf (0) 0 human/ECHS1 GO:0009083 branched-chain amino acid catabolic process ARBA:ARBA00091432 KEEP_AS_NON_CORE specific (1-20) 4 human/ECHS1 GO:0170035 L-amino acid catabolic process ARBA:ARBA00044574 MARK_AS_OVER_ANNOTATED leaf (0) 0 TOO_GENERAL true but uninformative general Overly general; superseded by GO:0009083 (branched-chain amino acid catabolic process) and GO:0006574 (L-valine catabolic process). human/EDEM1 GO:0005783 endoplasmic reticulum ARBA:ARBA00028672 ACCEPT general (21-200) 100 human/EDEM1 GO:0036503 ERAD pathway ARBA:ARBA00029018 ACCEPT specific (1-20) 3 human/EDEM2 GO:0009100 glycoprotein metabolic process ARBA:ARBA00027558 MARK_AS_OVER_ANNOTATED general (21-200) 66 TOO_GENERAL true but uninformative general Over-general parent process; the specific glycan-trimming/ERAD terms are preferred. human/EDEM3 GO:0005783 endoplasmic reticulum ARBA:ARBA00028672 ACCEPT general (21-200) 100 human/EDEM3 GO:0006516 glycoprotein catabolic process ARBA:ARBA00085471 KEEP_AS_NON_CORE specific (1-20) 11 human/EEFSEC GO:0001514 selenocysteine incorporation ARBA:ARBA00090133 ACCEPT leaf (0) 0 human/EGF GO:0007173 epidermal growth factor receptor signaling pathway ARBA:ARBA00034174 ACCEPT specific (1-20) 3 human/EGF GO:0008284 positive regulation of cell population proliferation ARBA:ARBA00027538 KEEP_AS_NON_CORE general (21-200) 85 human/EGF GO:0043410 positive regulation of MAPK cascade ARBA:ARBA00027228 ACCEPT specific (1-20) 10 human/EGF GO:0051049 regulation of transport ARBA:ARBA00027251 MARK_AS_OVER_ANNOTATED very general (>200 descendants) 960 INDIRECT_EFFECT overreach downstream The ARBA term likely reflects assorted downstream transport effects of EGFR signaling and should not be retained as a precise EGF process annotation. human/EGF GO:0160108 animal gross anatomical part developmental process ARBA:ARBA00098139 MARK_AS_OVER_ANNOTATED very general (>200 descendants) 3010 UNCLASSIFIED unclassified The annotation is not grossly false, but it loses the mechanistic specificity of EGF receptor ligand activity and EGFR signaling. human/EGFR GO:0043235 receptor complex ARBA:ARBA00029086 ACCEPT general (21-200) 113 human/EGFR GO:0070374 positive regulation of ERK1 and ERK2 cascade ARBA:ARBA00085202 ACCEPT leaf (0) 0 human/EGR2 GO:0005654 nucleoplasm ARBA:ARBA00026290 ACCEPT general (21-200) 65 human/EHD1 GO:0032456 endocytic recycling ARBA:ARBA00084270 ACCEPT specific (1-20) 5 human/EHD3 GO:0032456 endocytic recycling ARBA:ARBA00084270 ACCEPT specific (1-20) 5 human/EIF2AK1 GO:0006446 regulation of translational initiation ARBA:ARBA00035061 ACCEPT general (21-200) 46 human/EIF2AK1 GO:0006950 response to stress ARBA:ARBA00026300 ACCEPT very general (>200 descendants) 590 human/EIF2AK3 GO:0017148 negative regulation of translation ARBA:ARBA00027301 ACCEPT general (21-200) 37 human/EIF2AK3 GO:0034198 cellular response to amino acid starvation ARBA:ARBA00090477 UNDECIDED specific (1-20) 1 human/EIF2AK3 GO:0034976 response to endoplasmic reticulum stress ARBA:ARBA00027479 ACCEPT general (21-200) 23 human/EIF2B4 GO:0005085 guanyl-nucleotide exchange factor activity ARBA:ARBA00028188 ACCEPT leaf (0) 0 human/EIF2B4 GO:0005851 eukaryotic translation initiation factor 2B complex ARBA:ARBA00088579 ACCEPT leaf (0) 0 human/EIF2B4 GO:0007417 central nervous system development ARBA:ARBA00026561 KEEP_AS_NON_CORE very general (>200 descendants) 464 human/EIF2B4 GO:0048513 animal organ development ARBA:ARBA00029247 REMOVE very general (>200 descendants) 1888 INDIRECT overreach manual INDIRECT This is an over-annotation. EIF2B4 is essential for global protein synthesis, which is required for all cellular processes including organ development. However, there is no evidence that EIF2B4 plays a specific role in organ development beyond enabling general translation. The annotation is too broad and not informative for this gene. human/EIF2D GO:0043933 protein-containing complex organization ARBA:ARBA00026287 MARK_AS_OVER_ANNOTATED very general (>200 descendants) 321 TOO_GENERAL true but uninformative Generic Generic complex-organization term not specific to EIF2D's documented tRNA-delivery/recycling function; uninformative. human/EIF3E GO:0032991 protein-containing complex ARBA:ARBA00028902 MARK_AS_OVER_ANNOTATED very general (>200 descendants) 2083 TOO_GENERAL true but uninformative general While technically correct, this annotation is too general when more specific annotations (eIF3 complex, 43S/48S preinitiation complexes) exist. The specific complex annotations provide more informative functional context. human/ELAVL1 GO:0043488 regulation of mRNA stability ARBA:ARBA00027423 MODIFY general (21-200) 31 NEEDS_MORE_SPECIFIC true but uninformative replacement term ELAVL1 can have target- and partner-dependent effects, but the dominant directly demonstrated activity is stabilization of bound mRNAs; the more specific directional process is preferable here. human/ELAVL2 GO:0003730 mRNA 3'-UTR binding ARBA:ARBA00028422 ACCEPT specific (1-20) 1 human/ELAVL3 GO:0003730 mRNA 3'-UTR binding ARBA:ARBA00028422 ACCEPT specific (1-20) 1 human/ELAVL4 GO:0003730 mRNA 3'-UTR binding ARBA:ARBA00028422 ACCEPT specific (1-20) 1 human/ELOB GO:0000151 ubiquitin ligase complex ARBA:ARBA00029181 MARK_AS_OVER_ANNOTATED general (21-200) 52 TOO_GENERAL true but uninformative More specific More specific CRL2/CRL5 and VCB complex annotations capture the supported complex membership. human/ELOB GO:0005737 cytoplasm ARBA:ARBA00026971 MARK_AS_OVER_ANNOTATED very general (>200 descendants) 1146 TOO_GENERAL true but uninformative generic Use cytosol and nucleoplasm where available rather than generic cytoplasm. human/ELOC GO:0000151 ubiquitin ligase complex ARBA:ARBA00029181 MARK_AS_OVER_ANNOTATED general (21-200) 52 TOO_GENERAL true but uninformative More specific More specific Cul2-RING, Cul5-RING, and Elongin complex annotations capture the supported complex membership. human/ELOC GO:0005737 cytoplasm ARBA:ARBA00026971 MARK_AS_OVER_ANNOTATED very general (>200 descendants) 1146 TOO_GENERAL true but uninformative generic Use cytosol and nucleus/nucleoplasm annotations where available rather than generic cytoplasm. human/ELOVL1 GO:0030497 fatty acid elongation ARBA:ARBA00028259 ACCEPT specific (1-20) 4 human/ELOVL2 GO:0030497 fatty acid elongation ARBA:ARBA00028259 ACCEPT specific (1-20) 4 human/ELOVL3 GO:0030497 fatty acid elongation ARBA:ARBA00028259 KEEP_AS_NON_CORE specific (1-20) 4 human/ELOVL4 GO:0030497 fatty acid elongation ARBA:ARBA00028259 ACCEPT specific (1-20) 4 human/ELOVL5 GO:0030497 fatty acid elongation ARBA:ARBA00028259 ACCEPT specific (1-20) 4 human/ELOVL6 GO:0030497 fatty acid elongation ARBA:ARBA00028259 ACCEPT specific (1-20) 4 human/ELOVL7 GO:0030497 fatty acid elongation ARBA:ARBA00028259 ACCEPT specific (1-20) 4 human/EMC6 GO:0005737 cytoplasm ARBA:ARBA00026971 MARK_AS_OVER_ANNOTATED very general (>200 descendants) 1146 TOO_GENERAL true but uninformative Generic Generic and imprecise electronic assignment; the specific and experimentally supported compartment is the ER membrane (GO:0005789). human/ENDOG GO:0006308 DNA catabolic process ARBA:ARBA00035063 MODIFY specific (1-20) 3 NEEDS_MORE_SPECIFIC true but uninformative replacement term ARBA assigns a broad DNA catabolic process row, but direct human evidence shows ENDOG nuclease-dependent removal of mtDNA coupled to compensatory mitochondrial genome replication. human/ENDOU GO:0004540 RNA nuclease activity ARBA:ARBA00027859 ACCEPT general (21-200) 41 human/ENO3 GO:0006094 gluconeogenesis ARBA:ARBA00084701 ACCEPT leaf (0) 0 human/EPHA1 GO:0005005 transmembrane-ephrin receptor activity ARBA:ARBA00086055 ACCEPT leaf (0) 0 human/EPHA1 GO:0030155 regulation of cell adhesion ARBA:ARBA00027437 KEEP_AS_NON_CORE general (21-200) 193 human/ERBB2 GO:0016323 basolateral plasma membrane ARBA:ARBA00086715 KEEP_AS_NON_CORE leaf (0) 0 human/ERBB2 GO:0038128 ERBB2 signaling pathway ARBA:ARBA00087673 ACCEPT specific (1-20) 3 human/ERBB2 GO:0042127 regulation of cell population proliferation ARBA:ARBA00027546 KEEP_AS_NON_CORE very general (>200 descendants) 258 human/ERBB2 GO:0043410 positive regulation of MAPK cascade ARBA:ARBA00027228 ACCEPT specific (1-20) 10 human/ERC1 GO:0098793 presynapse ARBA:ARBA00028835 ACCEPT general (21-200) 52 human/ERCC4 GO:0009411 response to UV ARBA:ARBA00028103 ACCEPT specific (1-20) 17 human/ERG GO:1990837 sequence-specific double-stranded DNA binding ARBA:ARBA00028376 ACCEPT general (21-200) 48 human/ERLEC1 GO:0005783 endoplasmic reticulum ARBA:ARBA00028672 ACCEPT general (21-200) 100 human/ERLIN1 GO:0032933 SREBP signaling pathway ARBA:ARBA00087340 ACCEPT leaf (0) 0 human/ERLIN1 GO:0032991 protein-containing complex ARBA:ARBA00028902 KEEP_AS_NON_CORE very general (>200 descendants) 2083 human/ERLIN1 GO:0036503 ERAD pathway ARBA:ARBA00029018 ACCEPT specific (1-20) 3 human/ERLIN1 GO:0045541 negative regulation of cholesterol biosynthetic process ARBA:ARBA00085017 ACCEPT leaf (0) 0 human/ERLIN1 GO:0045717 negative regulation of fatty acid biosynthetic process ARBA:ARBA00084177 ACCEPT specific (1-20) 2 human/ERLIN2 GO:0032933 SREBP signaling pathway ARBA:ARBA00087340 ACCEPT leaf (0) 0 human/ERLIN2 GO:0032991 protein-containing complex ARBA:ARBA00028902 KEEP_AS_NON_CORE very general (>200 descendants) 2083 human/ERLIN2 GO:0036503 ERAD pathway ARBA:ARBA00029018 ACCEPT specific (1-20) 3 human/ERLIN2 GO:0045541 negative regulation of cholesterol biosynthetic process ARBA:ARBA00085017 ACCEPT leaf (0) 0 human/ERLIN2 GO:0045717 negative regulation of fatty acid biosynthetic process ARBA:ARBA00084177 ACCEPT specific (1-20) 2 human/ERN1 GO:0000287 magnesium ion binding ARBA:ARBA00028486 KEEP_AS_NON_CORE leaf (0) 0 human/ERN1 GO:0006401 RNA catabolic process ARBA:ARBA00027164 KEEP_AS_NON_CORE general (21-200) 64 human/ERN1 GO:0032991 protein-containing complex ARBA:ARBA00028902 MODIFY very general (>200 descendants) 2083 NEEDS_MORE_SPECIFIC true but uninformative replacement term Uninformative generic term; IRE1alpha forms stress-induced homo-oligomeric assemblies (Ire1 complex). human/ESPL1 GO:0000280 nuclear division ARBA:ARBA00028466 MODIFY general (21-200) 120 NEEDS_MORE_SPECIFIC true but uninformative replacement term The prediction is not wrong but is far too general: nuclear division covers mitosis and meiosis as a whole, whereas separase's contribution is one defined step, mitotic sister chromatid separation, which is already annotated from Reactome and supported by human depletion data. human/ESPL1 GO:0098813 nuclear chromosome segregation ARBA:ARBA00027947 ACCEPT general (21-200) 80 human/ETFA GO:0005739 mitochondrion ARBA:ARBA00026962 KEEP_AS_NON_CORE general (21-200) 70 human/ETFB GO:0005739 mitochondrion ARBA:ARBA00026962 KEEP_AS_NON_CORE general (21-200) 70 human/ETFDH GO:0005739 mitochondrion ARBA:ARBA00026962 KEEP_AS_NON_CORE general (21-200) 70 human/FADD GO:0001819 positive regulation of cytokine production ARBA:ARBA00028861 MARK_AS_OVER_ANNOTATED general (21-200) 86 INDIRECT_EFFECT overreach phenotype FADD is an adaptor for death-receptor, RIPK1, and antiviral signaling complexes; this term is too broad or phenotype-level for the direct work of the human FADD protein. human/FADD GO:0006952 defense response ARBA:ARBA00026315 MARK_AS_OVER_ANNOTATED general (21-200) 175 INDIRECT_EFFECT overreach phenotype FADD is an adaptor for death-receptor, RIPK1, and antiviral signaling complexes; this term is too broad or phenotype-level for the direct work of the human FADD protein. human/FADD GO:0030674 protein-macromolecule adaptor activity ARBA:ARBA00026473 ACCEPT general (21-200) 91 human/FADD GO:0050778 positive regulation of immune response ARBA:ARBA00028646 MARK_AS_OVER_ANNOTATED very general (>200 descendants) 217 INDIRECT_EFFECT overreach phenotype FADD is an adaptor for death-receptor, RIPK1, and antiviral signaling complexes; this term is too broad or phenotype-level for the direct work of the human FADD protein. human/FADD GO:0051707 response to other organism ARBA:ARBA00029118 MARK_AS_OVER_ANNOTATED general (21-200) 199 INDIRECT_EFFECT overreach phenotype FADD is an adaptor for death-receptor, RIPK1, and antiviral signaling complexes; this term is too broad or phenotype-level for the direct work of the human FADD protein. human/FADD GO:0097191 extrinsic apoptotic signaling pathway ARBA:ARBA00028297 MODIFY specific (1-20) 8 NEEDS_MORE_SPECIFIC true but uninformative replacement term FADD directly bridges death-domain receptors to initiator caspases, so the supported biological-process term is the FAS/TRAIL/TNFR branch rather than generic apoptosis or signaling. human/FADD GO:2001238 positive regulation of extrinsic apoptotic signaling pathway ARBA:ARBA00087870 MODIFY specific (1-20) 3 OTHER_TERM different term needed replacement term FADD directly bridges death-domain receptors to initiator caspases, so the supported biological-process term is the FAS/TRAIL/TNFR branch rather than generic apoptosis or signaling. human/FAF2 GO:0010498 proteasomal protein catabolic process ARBA:ARBA00028386 KEEP_AS_NON_CORE general (21-200) 21 human/FANCG GO:0006974 DNA damage response ARBA:ARBA00026271 ACCEPT general (21-200) 95 human/FANCM GO:0035825 homologous recombination ARBA:ARBA00027491 KEEP_AS_NON_CORE general (21-200) 22 human/FAR1 GO:0005777 peroxisome ARBA:ARBA00028589 ACCEPT specific (1-20) 16 human/FAR1 GO:0008610 lipid biosynthetic process ARBA:ARBA00027236 MARK_AS_OVER_ANNOTATED very general (>200 descendants) 258 TOO_GENERAL true but uninformative high-level A very high-level parent term. FAR1 does participate in lipid biosynthesis, but this generic ARBA-derived annotation is uninformative and redundant with the specific ether-lipid / wax / glycerophospholipid biosynthetic process annotations. human/FAR1 GO:0016620 oxidoreductase activity, acting on the aldehyde or oxo group of donors, NAD or NADP as acceptor ARBA:ARBA00028482 MARK_AS_OVER_ANNOTATED general (21-200) 80 TOO_GENERAL true but uninformative generic This term describes oxidation of an aldehyde/oxo donor with NAD(P) as acceptor. The physiological FAR1 reaction reduces fatty acyl-CoA (with NADPH as donor) to a fatty alcohol; the aldehyde is a transient intermediate and the acceptor/donor direction of this generic term does not accurately capture the enzyme's function. Better captured by the specific alcohol-forming acyl-CoA reductase term (GO:0102965). Generic ARBA over-annotation. human/FAR1 GO:1901568 fatty acid derivative metabolic process ARBA:ARBA00026357 MARK_AS_OVER_ANNOTATED general (21-200) 69 TOO_GENERAL true but uninformative Generic Generic high-level process term. FAR1's product (fatty alcohol) is a fatty acid derivative, so the annotation is not wrong, but it is uninformative and redundant with the specific biosynthetic-process annotations. Generic ARBA over-annotation. human/FAR2 GO:0005777 peroxisome ARBA:ARBA00028589 ACCEPT specific (1-20) 16 human/FAR2 GO:0010025 wax biosynthetic process ARBA:ARBA00091407 ACCEPT leaf (0) 0 human/FAS GO:0009986 cell surface ARBA:ARBA00027349 ACCEPT specific (1-20) 14 human/FAS GO:0031265 CD95 death-inducing signaling complex ARBA:ARBA00086566 ACCEPT leaf (0) 0 human/FAS GO:0042981 regulation of apoptotic process ARBA:ARBA00027086 ACCEPT very general (>200 descendants) 218 human/FAS GO:0097191 extrinsic apoptotic signaling pathway ARBA:ARBA00028297 ACCEPT specific (1-20) 8 human/FASLG GO:0005102 signaling receptor binding ARBA:ARBA00027239 MODIFY very general (>200 descendants) 380 NEEDS_MORE_SPECIFIC true but uninformative replacement term FASLG is a TNF-family ligand whose informative binding activity is engagement of the FAS death receptor, not generic signaling-receptor or TNF-receptor-superfamily binding. human/FASN GO:0006631 fatty acid metabolic process ARBA:ARBA00028669 KEEP_AS_NON_CORE general (21-200) 94 human/FASN GO:0008610 lipid biosynthetic process ARBA:ARBA00027236 KEEP_AS_NON_CORE very general (>200 descendants) 258 human/FBXL5 GO:0055080 monoatomic cation homeostasis ARBA:ARBA00027675 KEEP_AS_NON_CORE general (21-200) 89 human/FBXL5 GO:0098771 inorganic ion homeostasis ARBA:ARBA00028888 KEEP_AS_NON_CORE general (21-200) 79 human/FBXO17 GO:0005737 cytoplasm ARBA:ARBA00026971 ACCEPT very general (>200 descendants) 1146 human/FBXO27 GO:0005737 cytoplasm ARBA:ARBA00026971 KEEP_AS_NON_CORE very general (>200 descendants) 1146 human/FBXO43 GO:0010948 negative regulation of cell cycle process ARBA:ARBA00027265 ACCEPT general (21-200) 117 human/FBXO5 GO:0010948 negative regulation of cell cycle process ARBA:ARBA00027265 KEEP_AS_NON_CORE general (21-200) 117 human/FBXW12 GO:0005737 cytoplasm ARBA:ARBA00026971 KEEP_AS_NON_CORE very general (>200 descendants) 1146 human/FBXW5 GO:0010564 regulation of cell cycle process ARBA:ARBA00027431 KEEP_AS_NON_CORE very general (>200 descendants) 338 human/FBXW7 GO:0031146 SCF-dependent proteasomal ubiquitin-dependent protein catabolic process ARBA:ARBA00084384 ACCEPT leaf (0) 0 human/FBXW7 GO:0042752 regulation of circadian rhythm ARBA:ARBA00088520 KEEP_AS_NON_CORE general (21-200) 21 human/FBXW7 GO:0048731 system development ARBA:ARBA00027702 MARK_AS_OVER_ANNOTATED very general (>200 descendants) 2438 TOO_GENERAL true but uninformative Uninformative Uninformatively general; FBXW7 has specific developmental roles (Notch signaling, bone, neurodevelopment) better captured by more precise terms. human/FBXW7 GO:1901800 positive regulation of proteasomal protein catabolic process ARBA:ARBA00091269 KEEP_AS_NON_CORE specific (1-20) 4 human/FBXW7 GO:1903378 positive regulation of oxidative stress-induced neuron intrinsic apoptotic signaling pathway ARBA:ARBA00088649 KEEP_AS_NON_CORE leaf (0) 0 human/FBXW7 GO:2000060 positive regulation of ubiquitin-dependent protein catabolic process ARBA:ARBA00087687 KEEP_AS_NON_CORE specific (1-20) 3 human/FBXW7 GO:2001205 negative regulation of osteoclast development ARBA:ARBA00088112 KEEP_AS_NON_CORE leaf (0) 0 human/FCER1G GO:0050776 regulation of immune response ARBA:ARBA00028647 ACCEPT very general (>200 descendants) 505 human/FCER1G GO:0098797 plasma membrane protein complex ARBA:ARBA00028841 ACCEPT very general (>200 descendants) 309 human/FDFT1 GO:0005783 endoplasmic reticulum ARBA:ARBA00028672 ACCEPT general (21-200) 100 human/FDFT1 GO:0006694 steroid biosynthetic process ARBA:ARBA00028726 ACCEPT general (21-200) 29 human/FDFT1 GO:0016020 membrane ARBA:ARBA00028763 ACCEPT very general (>200 descendants) 895 human/FDPS GO:0006695 cholesterol biosynthetic process ARBA:ARBA00087369 KEEP_AS_NON_CORE leaf (0) 0 human/FECH GO:0005506 iron ion binding ARBA:ARBA00044836 KEEP_AS_NON_CORE specific (1-20) 2 human/FECH GO:0006785 heme B biosynthetic process ARBA:ARBA00093713 ACCEPT leaf (0) 0 human/FECH GO:0051537 2 iron, 2 sulfur cluster binding NEW leaf (0) 0 human/FEN1 GO:0004520 DNA endonuclease activity ARBA:ARBA00029205 ACCEPT general (21-200) 28 human/FEN1 GO:0006310 DNA recombination ARBA:ARBA00028026 KEEP_AS_NON_CORE general (21-200) 85 human/FERMT2 GO:0030335 positive regulation of cell migration ARBA:ARBA00028907 KEEP_AS_NON_CORE general (21-200) 68 human/FGF1 GO:0001658 branching involved in ureteric bud morphogenesis ARBA:ARBA00089877 KEEP_AS_NON_CORE specific (1-20) 2 human/FGF1 GO:0005104 fibroblast growth factor receptor binding ARBA:ARBA00085803 ACCEPT specific (1-20) 3 human/FGF1 GO:0008284 positive regulation of cell population proliferation ARBA:ARBA00027538 ACCEPT general (21-200) 85 human/FGF1 GO:0008543 fibroblast growth factor receptor signaling pathway ARBA:ARBA00084988 ACCEPT specific (1-20) 12 human/FGF1 GO:1903672 positive regulation of sprouting angiogenesis ARBA:ARBA00089251 ACCEPT leaf (0) 0 human/FGF1 GO:1905330 regulation of morphogenesis of an epithelium ARBA:ARBA00087145 KEEP_AS_NON_CORE general (21-200) 48 human/FGF1 GO:2000544 regulation of endothelial cell chemotaxis to fibroblast growth factor ARBA:ARBA00087597 KEEP_AS_NON_CORE specific (1-20) 2 human/FGF19 GO:0046326 positive regulation of D-glucose import across plasma membrane ARBA:ARBA00093151 KEEP_AS_NON_CORE leaf (0) 0 human/FGF2 GO:0001658 branching involved in ureteric bud morphogenesis ARBA:ARBA00089877 KEEP_AS_NON_CORE specific (1-20) 2 human/FGF2 GO:0008543 fibroblast growth factor receptor signaling pathway ARBA:ARBA00084988 ACCEPT specific (1-20) 12 human/FGF2 GO:1903672 positive regulation of sprouting angiogenesis ARBA:ARBA00089251 KEEP_AS_NON_CORE leaf (0) 0 human/FGF2 GO:1905330 regulation of morphogenesis of an epithelium ARBA:ARBA00087145 KEEP_AS_NON_CORE general (21-200) 48 human/FGF2 GO:2000544 regulation of endothelial cell chemotaxis to fibroblast growth factor ARBA:ARBA00087597 KEEP_AS_NON_CORE specific (1-20) 2 human/FGF21 GO:0046326 positive regulation of D-glucose import across plasma membrane ARBA:ARBA00093151 KEEP_AS_NON_CORE leaf (0) 0 human/FGF8 GO:0005105 type 1 fibroblast growth factor receptor binding ARBA:ARBA00085801 ACCEPT leaf (0) 0 human/FGF8 GO:0005111 type 2 fibroblast growth factor receptor binding ARBA:ARBA00085808 ACCEPT leaf (0) 0 human/FGFR1 GO:0017134 fibroblast growth factor binding ARBA:ARBA00085876 ACCEPT leaf (0) 0 human/FGFR1 GO:0043410 positive regulation of MAPK cascade ARBA:ARBA00027228 ACCEPT specific (1-20) 10 human/FGFR1 GO:0048699 generation of neurons ARBA:ARBA00027116 KEEP_AS_NON_CORE very general (>200 descendants) 357 human/FGFR1 GO:0048705 skeletal system morphogenesis ARBA:ARBA00043345 KEEP_AS_NON_CORE general (21-200) 39 human/FGFR2 GO:0033688 regulation of osteoblast proliferation ARBA:ARBA00084763 ACCEPT specific (1-20) 2 human/FGFR2 GO:0043009 chordate embryonic development ARBA:ARBA00027425 KEEP_AS_NON_CORE general (21-200) 101 human/FGFR2 GO:0043410 positive regulation of MAPK cascade ARBA:ARBA00027228 ACCEPT specific (1-20) 10 human/FGFR2 GO:0045595 regulation of cell differentiation ARBA:ARBA00028479 ACCEPT very general (>200 descendants) 697 human/FGFR2 GO:0048562 embryonic organ morphogenesis ARBA:ARBA00043470 ACCEPT general (21-200) 56 human/FGFR2 GO:0048705 skeletal system morphogenesis ARBA:ARBA00043345 ACCEPT general (21-200) 39 human/FGFR2 GO:1904888 cranial skeletal system development ARBA:ARBA00089035 ACCEPT specific (1-20) 12 human/FGFR3 GO:0001503 ossification ARBA:ARBA00090120 KEEP_AS_NON_CORE specific (1-20) 15 human/FGFR3 GO:0017134 fibroblast growth factor binding ARBA:ARBA00085876 ACCEPT leaf (0) 0 human/FGFR3 GO:0043410 positive regulation of MAPK cascade ARBA:ARBA00027228 ACCEPT specific (1-20) 10 human/FGFR3 GO:0051216 cartilage development ARBA:ARBA00089273 KEEP_AS_NON_CORE general (21-200) 29 human/FGFR3 GO:0060349 bone morphogenesis ARBA:ARBA00090827 KEEP_AS_NON_CORE general (21-200) 30 human/FGFR4 GO:0010468 regulation of gene expression ARBA:ARBA00028334 KEEP_AS_NON_CORE very general (>200 descendants) 874 human/FGFR4 GO:0017134 fibroblast growth factor binding ARBA:ARBA00085876 ACCEPT leaf (0) 0 human/FGFR4 GO:0043410 positive regulation of MAPK cascade ARBA:ARBA00027228 ACCEPT specific (1-20) 10 human/FGFR4 GO:0070857 regulation of bile acid biosynthetic process ARBA:ARBA00086465 MODIFY specific (1-20) 2 NEEDS_MORE_SPECIFIC true but uninformative replacement term FGFR4 is the hepatocyte receptor kinase through which intestinal FGF15/19 (with beta-Klotho) represses CYP7A1 and bile acid synthesis; FGFR4 performs the signal-transducing step, so this is genuine participation. The direction is known (repression), so the generic parent should be replaced by its child GO:0070858. human/FKBP4 GO:0005528 FK506 binding ARBA:ARBA00086865 ACCEPT leaf (0) 0 human/FKBP4 GO:0006457 protein folding ARBA:ARBA00027200 KEEP_AS_NON_CORE specific (1-20) 7 human/FKBP5 GO:0005528 FK506 binding ARBA:ARBA00086865 ACCEPT leaf (0) 0 human/FKBP5 GO:0006457 protein folding ARBA:ARBA00027200 KEEP_AS_NON_CORE specific (1-20) 7 human/FKBP5 GO:0031072 heat shock protein binding ARBA:ARBA00084805 ACCEPT specific (1-20) 3 human/FKBP8 GO:0007165 signal transduction ARBA:ARBA00029050 KEEP_AS_NON_CORE very general (>200 descendants) 937 human/FLAD1 GO:0005737 cytoplasm ARBA:ARBA00026971 MARK_AS_OVER_ANNOTATED very general (>200 descendants) 1146 TOO_GENERAL true but uninformative generic ARBA electronic annotation to the generic parent 'cytoplasm'. The specific cytosol localization (isoform 2) is experimentally established; this generic parent is redundant with the more precise GO:0005829 cytosol IDA annotation. human/FN1 GO:0002020 protease binding ARBA:ARBA00087861 ACCEPT specific (1-20) 2 human/FNTB GO:0004659 prenyltransferase activity ARBA:ARBA00027066 MODIFY general (21-200) 39 NEEDS_MORE_SPECIFIC true but uninformative replacement term ARBA-predicted prenyltransferase activity. This is a parent of protein farnesyltransferase activity (GO:0004660); correct but less informative. Replace with the specific experimentally supported term. human/FOXO1 GO:0005654 nucleoplasm ARBA:ARBA00026290 ACCEPT general (21-200) 65 human/FOXO1 GO:0008013 beta-catenin binding ARBA:ARBA00093020 ACCEPT leaf (0) 0 human/FRS2 GO:0005104 fibroblast growth factor receptor binding ARBA:ARBA00085803 ACCEPT specific (1-20) 3 human/FRS2 GO:0008543 fibroblast growth factor receptor signaling pathway ARBA:ARBA00084988 ACCEPT specific (1-20) 12 human/FRS3 GO:0005104 fibroblast growth factor receptor binding ARBA:ARBA00085803 ACCEPT specific (1-20) 3 human/FRS3 GO:0005886 plasma membrane ARBA:ARBA00027801 ACCEPT very general (>200 descendants) 415 human/FRS3 GO:0008543 fibroblast growth factor receptor signaling pathway ARBA:ARBA00084988 ACCEPT specific (1-20) 12 human/FXN GO:0007005 mitochondrion organization ARBA:ARBA00026723 MARK_AS_OVER_ANNOTATED general (21-200) 37 INDIRECT_EFFECT overreach secondary While FXN deficiency affects mitochondrial structure, this is a secondary consequence of impaired Fe-S cluster assembly affecting respiratory chain complexes rather than a direct function of FXN in mitochondrial organization. human/FXN GO:0030003 intracellular monoatomic cation homeostasis ARBA:ARBA00028070 MARK_AS_OVER_ANNOTATED general (21-200) 75 INDIRECT_EFFECT overreach indirect Very general term; effect on homeostasis is indirect. human/FXN GO:0098771 inorganic ion homeostasis ARBA:ARBA00028888 MARK_AS_OVER_ANNOTATED general (21-200) 79 INDIRECT_EFFECT overreach indirect Very general term; FXN's effect on ion homeostasis is indirect through Fe-S cluster assembly. human/FZD7 GO:0030165 PDZ domain binding ARBA:ARBA00085880 ACCEPT leaf (0) 0 human/FZD7 GO:0060070 canonical Wnt signaling pathway ARBA:ARBA00026624 ACCEPT specific (1-20) 5 human/G6PC1 GO:0048878 chemical homeostasis ARBA:ARBA00026985 MARK_AS_OVER_ANNOTATED general (21-200) 154 TOO_GENERAL true but uninformative uninformative The specific and experimentally supported role is glucose homeostasis (GO:0042593), retained as a core function; chemical homeostasis is an uninformative parent term. human/GAA GO:0005980 glycogen catabolic process ARBA:ARBA00034181 ACCEPT specific (1-20) 1 human/GAA GO:0005984 disaccharide metabolic process ARBA:ARBA00027065 MARK_AS_OVER_ANNOTATED specific (1-20) 20 UNCLASSIFIED unclassified GAA can cleave the disaccharide maltose in vitro, but its physiological substrate is lysosomal glycogen (a polymer), not free disaccharides; dietary disaccharide metabolism is the role of intestinal sucrase-isomaltase/maltase-glucoamylase. This is an over-annotation of the in-vitro substrate scope rather than the biological function. human/GABARAP GO:0005543 phospholipid binding ARBA:ARBA00027145 ACCEPT specific (1-20) 19 human/GABARAP GO:0005776 autophagosome ARBA:ARBA00033591 ACCEPT specific (1-20) 4 human/GABARAP GO:0016236 macroautophagy ARBA:ARBA00027245 ACCEPT general (21-200) 34 human/GABARAP GO:0031625 ubiquitin protein ligase binding ARBA:ARBA00028807 KEEP_AS_NON_CORE leaf (0) 0 human/GADD45A GO:0046330 positive regulation of JNK cascade ARBA:ARBA00093162 ACCEPT leaf (0) 0 human/GADD45A GO:1900745 positive regulation of p38MAPK cascade ARBA:ARBA00085720 ACCEPT leaf (0) 0 human/GADD45B GO:0046330 positive regulation of JNK cascade ARBA:ARBA00093162 ACCEPT leaf (0) 0 human/GADD45B GO:1900745 positive regulation of p38MAPK cascade ARBA:ARBA00085720 ACCEPT leaf (0) 0 human/GADD45G GO:0043410 positive regulation of MAPK cascade ARBA:ARBA00027228 MODIFY specific (1-20) 10 NEEDS_MORE_SPECIFIC true but uninformative replacement term MODIFY. This is correct but too general. GADD45G specifically activates p38 MAPK and JNK pathways via MTK1/MEKK4. More specific terms already exist: GO:0046330 (positive regulation of JNK cascade) and GO:1900745 (positive regulation of p38MAPK cascade). human/GAL3ST1 GO:0050694 galactose 3-O-sulfotransferase activity ARBA:ARBA00089439 ACCEPT specific (1-20) 1 human/GALNT1 GO:0016266 protein O-linked glycosylation via N-acetylgalactosamine ARBA:ARBA00086939 ACCEPT specific (1-20) 1 human/GART GO:0003824 catalytic activity ARBA:ARBA00027533 MARK_AS_OVER_ANNOTATED very general (>200 descendants) 6405 TOO_GENERAL true but uninformative general GART is an enzyme, so this ARBA-derived term is not wrong, but it is far too general to be informative when the specific EC 6.3.4.13 / 2.1.2.2 / 6.3.3.1 activities are already annotated. human/GAS6 GO:0005796 Golgi lumen ARBA:ARBA00028705 KEEP_AS_NON_CORE specific (1-20) 2 human/GAS6 GO:0007166 cell surface receptor signaling pathway ARBA:ARBA00029053 ACCEPT very general (>200 descendants) 403 human/GAS6 GO:0016477 cell migration ARBA:ARBA00028795 KEEP_AS_NON_CORE very general (>200 descendants) 257 human/GAS6 GO:0030154 cell differentiation ARBA:ARBA00027429 KEEP_AS_NON_CORE very general (>200 descendants) 1345 human/GAS6 GO:0031669 cellular response to nutrient levels ARBA:ARBA00034580 MARK_AS_OVER_ANNOTATED general (21-200) 72 UNCLASSIFIED unclassified cellular response to nutrient levels overstates or obscures the direct GAS6 product function. human/GAS6 GO:0043277 apoptotic cell clearance ARBA:ARBA00086522 ACCEPT specific (1-20) 7 human/GAS6 GO:2000270 negative regulation of fibroblast apoptotic process ARBA:ARBA00088175 KEEP_AS_NON_CORE leaf (0) 0 human/GATA3 GO:0009653 anatomical structure morphogenesis ARBA:ARBA00026583 KEEP_AS_NON_CORE very general (>200 descendants) 1501 human/GATA3 GO:0030154 cell differentiation ARBA:ARBA00027429 ACCEPT very general (>200 descendants) 1345 human/GATA3 GO:0048731 system development ARBA:ARBA00027702 KEEP_AS_NON_CORE very general (>200 descendants) 2438 human/GATA3 GO:0050793 regulation of developmental process ARBA:ARBA00028689 ACCEPT very general (>200 descendants) 1542 human/GATA3 GO:1990837 sequence-specific double-stranded DNA binding ARBA:ARBA00028376 ACCEPT general (21-200) 48 human/GATA3 GO:0005654 nucleoplasm ARBA:ARBA00026290 ACCEPT general (21-200) 65 human/GATA4 GO:0005654 nucleoplasm ARBA:ARBA00026290 ACCEPT general (21-200) 65 human/GATA4 GO:0007507 heart development ARBA:ARBA00028650 ACCEPT very general (>200 descendants) 281 human/GATA4 GO:0009653 anatomical structure morphogenesis ARBA:ARBA00026583 MODIFY very general (>200 descendants) 1501 NEEDS_MORE_SPECIFIC true but uninformative replacement term Too general; the best-supported morphogenetic role is heart morphogenesis. human/GATA4 GO:0009888 tissue development ARBA:ARBA00028065 MODIFY very general (>200 descendants) 1023 OTHER_TERM different term needed replacement term Too general; replace with heart development, the primary tissue context. human/GATA4 GO:0030154 cell differentiation ARBA:ARBA00027429 MODIFY very general (>200 descendants) 1345 NEEDS_MORE_SPECIFIC true but uninformative replacement term Too general. GATA4 promotes cardiomyocyte differentiation in progenitor cultures, so cardiac muscle cell differentiation is the informative term. human/GBA GO:0008422 beta-glucosidase activity ARBA:ARBA00028897 KEEP_AS_NON_CORE specific (1-20) 20 human/GBA GO:0016241 regulation of macroautophagy ARBA:ARBA00086966 MARK_AS_OVER_ANNOTATED general (21-200) 24 INDIRECT_EFFECT overreach indirect GCase deficiency compromises autophagic lysosome reformation and macroautophagy (PMID:27378698), but this is an indirect, disease-state consequence of losing the catabolic enzyme rather than a direct regulatory role of GBA. Over-annotation of the causal chain. human/GBA GO:0030163 protein catabolic process ARBA:ARBA00027403 REMOVE general (21-200) 66 WRONG_PROCESS wrong manual WRONG_PROCESS This IEA is a spurious/over-general electronic inference. GBA does not catalyse protein catabolism; it hydrolyses glucosylceramide. The apparent link runs through lysosomal/autophagic dysfunction in GCase-deficient cells, which does not justify a direct 'protein catabolic process' annotation. human/GBA GO:0042176 regulation of protein catabolic process ARBA:ARBA00027460 MARK_AS_OVER_ANNOTATED general (21-200) 43 INDIRECT_EFFECT overreach downstream GCase loss impairs lysosomal degradation of substrates such as alpha-synuclein, but GBA does not itself regulate protein catabolism; this electronic mapping over-annotates a downstream disease phenotype. human/GBA GO:0042391 regulation of membrane potential ARBA:ARBA00028934 REMOVE general (21-200) 154 INDIRECT overreach manual INDIRECT Over-general electronic inference with no biological support for a direct role. Changes in mitochondrial membrane potential in GCase-deficient cells (PMID:26388395) are secondary consequences of enzyme loss, not a molecular function of GBA. human/GBA1 GO:0016241 regulation of macroautophagy ARBA:ARBA00086966 KEEP_AS_NON_CORE general (21-200) 24 human/GBA1 GO:0030163 protein catabolic process ARBA:ARBA00027403 MODIFY general (21-200) 66 NEEDS_MORE_SPECIFIC true but uninformative replacement term Use regulation of lysosomal protein catabolic process to reflect the indirect lysosomal proteostasis role. human/GBA1 GO:0042176 regulation of protein catabolic process ARBA:ARBA00027460 MODIFY general (21-200) 43 NEEDS_MORE_SPECIFIC true but uninformative replacement term Use regulation of lysosomal protein catabolic process, which matches the alpha-synuclein/lysosomal degradation context more closely. human/GBA1 GO:0042391 regulation of membrane potential ARBA:ARBA00028934 MARK_AS_OVER_ANNOTATED general (21-200) 154 INDIRECT_EFFECT overreach phenotype Mitochondrial and neuronal electrophysiology phenotypes are downstream disease contexts and should not be propagated as a GBA1 core GO process. human/GCDH GO:0005739 mitochondrion ARBA:ARBA00026962 ACCEPT general (21-200) 70 human/GCG GO:0005102 signaling receptor binding ARBA:ARBA00027239 ACCEPT very general (>200 descendants) 380 human/GCH1 GO:0008217 regulation of blood pressure ARBA:ARBA00027471 KEEP_AS_NON_CORE general (21-200) 111 human/GCH1 GO:0042558 pteridine-containing compound metabolic process ARBA:ARBA00027196 ACCEPT general (21-200) 37 human/GCK GO:0006006 glucose metabolic process ARBA:ARBA00027390 ACCEPT specific (1-20) 7 human/GCK GO:0006163 purine nucleotide metabolic process ARBA:ARBA00026737 MARK_AS_OVER_ANNOTATED general (21-200) 130 UNCLASSIFIED unclassified Over-interpretation of ATP co-substrate usage. GCK does not metabolize purine nucleotides; ATP is a universal phosphoryl donor and this term misrepresents the gene's biological role. human/GCK GO:0032024 positive regulation of insulin secretion ARBA:ARBA00092024 ACCEPT specific (1-20) 1 human/GCK GO:0042593 glucose homeostasis ARBA:ARBA00087005 ACCEPT specific (1-20) 5 human/GCK GO:0046496 nicotinamide nucleotide metabolic process ARBA:ARBA00028393 REMOVE general (21-200) 31 WRONG_PROCESS wrong manual WRONG_PROCESS Demonstrably wrong electronic inference. Glucokinase does not participate in nicotinamide nucleotide (NAD/NADP) metabolism; there is no biochemical basis for this ARBA mapping, which should be removed. human/GCLC GO:0043066 negative regulation of apoptotic process ARBA:ARBA00027746 KEEP_AS_NON_CORE general (21-200) 79 human/GEMIN5 GO:0003730 mRNA 3'-UTR binding ARBA:ARBA00028422 ACCEPT specific (1-20) 1 human/GET1 GO:0090150 establishment of protein localization to membrane ARBA:ARBA00028450 KEEP_AS_NON_CORE general (21-200) 47 human/GFER GO:0015035 protein-disulfide reductase activity ARBA:ARBA00026550 MODIFY specific (1-20) 4 NEEDS_MORE_SPECIFIC true but uninformative replacement term Replace protein-disulfide reductase activity with sulfhydryl/thiol oxidase activity for GFER. human/GFPT1 GO:0006002 fructose 6-phosphate metabolic process ARBA:ARBA00084568 KEEP_AS_NON_CORE specific (1-20) 1 human/GFPT1 GO:0006112 energy reserve metabolic process ARBA:ARBA00026613 REMOVE specific (1-20) 4 WRONG_PROCESS wrong manual WRONG_PROCESS "Biologically incorrect. ""Energy reserve metabolic process"" concerns storage carbohydrate/lipid (glycogen, starch, triglyceride) metabolism and energy derivation. GFPT1 does the opposite: it diverts fructose 6-phosphate OUT of energy/glycolytic flux into aminosugar biosynthesis (the HBP). This is a clearly wrong electronic (ARBA) inference and should be removed." human/GFPT2 GO:0006002 fructose 6-phosphate metabolic process ARBA:ARBA00084568 ACCEPT specific (1-20) 1 human/GFPT2 GO:0006112 energy reserve metabolic process ARBA:ARBA00026613 REMOVE specific (1-20) 4 WRONG_PROCESS wrong manual WRONG_PROCESS GFAT2 diverts fructose 6-phosphate into hexosamine/UDP-GlcNAc biosynthesis, not into energy-reserve (glycogen/starch) metabolism; the ARBA mapping is wrong. human/GGPS1 GO:0006720 isoprenoid metabolic process ARBA:ARBA00027853 KEEP_AS_NON_CORE general (21-200) 200 human/GHSR GO:0007154 cell communication ARBA:ARBA00028945 KEEP_AS_NON_CORE very general (>200 descendants) 1207 human/GHSR GO:0023052 signaling ARBA:ARBA00026303 KEEP_AS_NON_CORE very general (>200 descendants) 1141 human/GHSR GO:0038023 signaling receptor activity ARBA:ARBA00027254 MODIFY very general (>200 descendants) 389 NEEDS_MORE_SPECIFIC true but uninformative replacement term GHSR is a peptide-hormone-binding GPCR, but the specific ghrelin/growth-hormone-secretagogue receptor activity is more informative than generic receptor or peptide-binding terms. human/GLA GO:0005576 extracellular region ARBA:ARBA00027128 KEEP_AS_NON_CORE very general (>200 descendants) 276 human/GLA GO:0046479 glycosphingolipid catabolic process ARBA:ARBA00092736 ACCEPT specific (1-20) 4 human/GLI2 GO:0003690 double-stranded DNA binding ARBA:ARBA00027852 ACCEPT general (21-200) 77 human/GLI2 GO:0007224 smoothened signaling pathway ARBA:ARBA00084926 ACCEPT specific (1-20) 7 human/GLI2 GO:0009653 anatomical structure morphogenesis ARBA:ARBA00026583 KEEP_AS_NON_CORE very general (>200 descendants) 1501 human/GLI2 GO:0010468 regulation of gene expression ARBA:ARBA00028334 MODIFY very general (>200 descendants) 874 NEEDS_MORE_SPECIFIC true but uninformative replacement term Too general to be useful on this gene. GLI2 is a sequence-specific RNA polymerase II transcription factor and the mechanism is known precisely - promoter binding at the GLI consensus followed by activation or repression - so the annotation should sit at GO:0006357 regulation of transcription by RNA polymerase II, which GLI2 already holds by IBA and which discards none of the evidence. Not an over-annotation, simply the wrong grain. human/GLI2 GO:0043565 sequence-specific DNA binding ARBA:ARBA00026779 MODIFY general (21-200) 60 NEEDS_MORE_SPECIFIC true but uninformative replacement term Correct but coarser than the evidence available for this gene, and moved to the same replacement as the three IDA rows for consistency. Every characterised GLI2 binding site is an RNA polymerase II cis-regulatory element, so GO:0000978 is both supported and more informative. human/GLI2 GO:0097542 ciliary tip ARBA:ARBA00044587 KEEP_AS_NON_CORE leaf (0) 0 human/GLI2 GO:0097546 ciliary base ARBA:ARBA00091132 KEEP_AS_NON_CORE leaf (0) 0 human/GLI3 GO:0003690 double-stranded DNA binding ARBA:ARBA00027852 MODIFY general (21-200) 77 NEEDS_MORE_SPECIFIC true but uninformative replacement term Correct but unnecessarily general: GLI3 does not bind duplex DNA indiscriminately, it reads a defined GLI consensus. The sequence-specific double-stranded term states what is actually known and is already supported by direct evidence elsewhere in this record. human/GLI3 GO:0009653 anatomical structure morphogenesis ARBA:ARBA00026583 KEEP_AS_NON_CORE very general (>200 descendants) 1501 human/GLI3 GO:0010468 regulation of gene expression ARBA:ARBA00028334 MODIFY very general (>200 descendants) 874 NEEDS_MORE_SPECIFIC true but uninformative replacement term Correct but several levels above what is known. GLI3 acts specifically at RNA polymerase II cis-regulatory elements, which the Pol II-specific regulation term states; the generic gene-expression parent adds nothing. human/GLI3 GO:0097542 ciliary tip ARBA:ARBA00044587 ACCEPT leaf (0) 0 human/GLI3 GO:0097546 ciliary base ARBA:ARBA00091132 ACCEPT leaf (0) 0 human/GLS GO:0006520 amino acid metabolic process ARBA:ARBA00026411 KEEP_AS_NON_CORE general (21-200) 183 human/GLS2 GO:0005759 mitochondrial matrix ARBA:ARBA00028628 ACCEPT specific (1-20) 17 human/GLS2 GO:0006520 amino acid metabolic process ARBA:ARBA00026411 KEEP_AS_NON_CORE general (21-200) 183 human/GLUD1 GO:0005525 GTP binding ARBA:ARBA00027026 KEEP_AS_NON_CORE leaf (0) 0 human/GLUD1 GO:0006538 L-glutamate catabolic process ARBA:ARBA00085448 ACCEPT specific (1-20) 1 human/GLUD1 GO:0043531 ADP binding ARBA:ARBA00085519 ACCEPT leaf (0) 0 human/GLUD1 GO:0070728 L-leucine binding ARBA:ARBA00084284 KEEP_AS_NON_CORE leaf (0) 0 human/GLUD2 GO:0005525 GTP binding ARBA:ARBA00027026 KEEP_AS_NON_CORE leaf (0) 0 human/GLUD2 GO:0006538 L-glutamate catabolic process ARBA:ARBA00085448 ACCEPT specific (1-20) 1 human/GLUD2 GO:0043531 ADP binding ARBA:ARBA00085519 ACCEPT leaf (0) 0 human/GLUD2 GO:0070728 L-leucine binding ARBA:ARBA00084284 KEEP_AS_NON_CORE leaf (0) 0 human/GM2A GO:0046479 glycosphingolipid catabolic process ARBA:ARBA00092736 ACCEPT specific (1-20) 4 human/GNPNAT1 GO:0005737 cytoplasm ARBA:ARBA00026971 KEEP_AS_NON_CORE very general (>200 descendants) 1146 human/GOT1 GO:0006533 L-aspartate catabolic process ARBA:ARBA00085434 ACCEPT leaf (0) 0 human/GOT2 GO:0006533 L-aspartate catabolic process ARBA:ARBA00085434 ACCEPT leaf (0) 0 human/GPC2 GO:0043202 lysosomal lumen ARBA:ARBA00029034 KEEP_AS_NON_CORE specific (1-20) 3 human/GPC4 GO:0043202 lysosomal lumen ARBA:ARBA00029034 ACCEPT specific (1-20) 3 human/GPC6 GO:0043202 lysosomal lumen ARBA:ARBA00029034 KEEP_AS_NON_CORE specific (1-20) 3 human/GPD2 GO:0005743 mitochondrial inner membrane ARBA:ARBA00028608 ACCEPT general (21-200) 23 human/GPHN GO:0003824 catalytic activity ARBA:ARBA00027533 MARK_AS_OVER_ANNOTATED very general (>200 descendants) 6405 TOO_GENERAL true but uninformative Uninformative Uninformative generic ARBA prediction superseded by the specific MoCo-biosynthesis MF terms. human/GPHN GO:0050808 synapse organization ARBA:ARBA00029184 MARK_AS_OVER_ANNOTATED general (21-200) 75 TOO_GENERAL true but uninformative general Over-general ARBA term superseded by the specific glycine/GABAAR receptor-clustering annotations. human/GPHN GO:0072657 protein localization to membrane ARBA:ARBA00029167 MARK_AS_OVER_ANNOTATED general (21-200) 53 TOO_GENERAL true but uninformative general Over-general; the specific receptor-clustering and adaptor-activity annotations capture the biology more precisely. human/GPI GO:0016853 isomerase activity ARBA:ARBA00026936 MARK_AS_OVER_ANNOTATED very general (>200 descendants) 281 TOO_GENERAL true but uninformative generic This is the generic grandparent of the specific glucose-6-phosphate isomerase activity that is already annotated; the specific term should be preferred. human/GPR161 GO:0007189 adenylate cyclase-activating G protein-coupled receptor signaling pathway ARBA:ARBA00029026 ACCEPT specific (1-20) 9 human/GPR161 GO:0035591 signaling adaptor activity ARBA:ARBA00090724 ACCEPT specific (1-20) 5 human/GPR161 GO:0045879 negative regulation of smoothened signaling pathway ARBA:ARBA00086554 ACCEPT specific (1-20) 1 human/GPR161 GO:0098804 non-motile cilium membrane ARBA:ARBA00091729 ACCEPT leaf (0) 0 human/GPR37 GO:0007193 adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway ARBA:ARBA00043458 ACCEPT specific (1-20) 9 human/GPR37 GO:0008528 G protein-coupled peptide receptor activity ARBA:ARBA00028017 ACCEPT general (21-200) 56 human/GPR37 GO:0036505 prosaposin receptor activity ARBA:ARBA00091675 ACCEPT leaf (0) 0 human/GPR37 GO:0042277 peptide binding ARBA:ARBA00043490 KEEP_AS_NON_CORE specific (1-20) 4 human/GRAMD1A GO:0044232 organelle membrane contact site ARBA:ARBA00028235 ACCEPT specific (1-20) 15 human/GRAP2 GO:0005829 cytosol ARBA:ARBA00029243 ACCEPT general (21-200) 73 human/GRB2 GO:0005829 cytosol ARBA:ARBA00029243 ACCEPT general (21-200) 73 human/GRB2 GO:0007265 Ras protein signal transduction ARBA:ARBA00044394 ACCEPT leaf (0) 0 human/GRHPR GO:0106345 glyoxylate reductase activity ARBA:ARBA00090466 ACCEPT specific (1-20) 2 human/GRID1 GO:0007165 signal transduction ARBA:ARBA00029050 MODIFY very general (>200 descendants) 937 OTHER_TERM different term needed replacement term """Signal transduction"" is the least informative possible way to record the best-established thing about GluD1. GO:0099557 names the actual mechanism: presynaptic neurexin-cerebellin binding to the GluD1 ATD is converted, through short cytoplasmic motifs, into changes in postsynaptic receptor content." human/GRID1 GO:0048167 regulation of synaptic plasticity ARBA:ARBA00033936 ACCEPT general (21-200) 29 human/GRID1 GO:0060078 regulation of postsynaptic membrane potential ARBA:ARBA00026619 ACCEPT specific (1-20) 16 human/GRPEL1 GO:0042802 identical protein binding ARBA:ARBA00027930 ACCEPT specific (1-20) 1 human/GSK3B GO:0009968 negative regulation of signal transduction ARBA:ARBA00027208 MARK_AS_OVER_ANNOTATED very general (>200 descendants) 244 TOO_GENERAL true but uninformative More informative For GO:0009968 (negative regulation of signal transduction), the IEA annotation with qualifier involved_in from GO_REF:0000117 may reflect a real assay result or interaction, but this GO term does not identify the specific kinase/substrate, pathway, or localization annotation that explains GSK3B's role in ATP-dependent serine/threonine phosphorylation of primed protein substrates, especially Wnt/beta-catenin, glycogen/insulin, tau, and protein-turnover substrates. More informative gene-specific annotations are present, so this is marked over-annotated rather than accepted as a core function. human/GSK3B GO:0019082 viral protein processing ARBA:ARBA00092097 KEEP_AS_NON_CORE leaf (0) 0 human/GSK3B GO:0031398 positive regulation of protein ubiquitination ARBA:ARBA00028317 ACCEPT specific (1-20) 9 human/GSK3B GO:0032436 positive regulation of proteasomal ubiquitin-dependent protein catabolic process ARBA:ARBA00084330 ACCEPT specific (1-20) 2 human/GSK3B GO:0034236 protein kinase A catalytic subunit binding ARBA:ARBA00090631 KEEP_AS_NON_CORE leaf (0) 0 human/GSK3B GO:2000077 negative regulation of type B pancreatic cell development ARBA:ARBA00087693 KEEP_AS_NON_CORE leaf (0) 0 human/GTF2F2 GO:0006368 transcription elongation by RNA polymerase II ARBA:ARBA00086159 ACCEPT specific (1-20) 2 human/GTF2F2 GO:0016591 RNA polymerase II, holoenzyme ARBA:ARBA00028038 KEEP_AS_NON_CORE specific (1-20) 11 human/GTF2F2 GO:0090575 RNA polymerase II transcription regulator complex ARBA:ARBA00028248 KEEP_AS_NON_CORE general (21-200) 44 human/GTPBP1 GO:1904678 alpha-aminoacyl-tRNA binding ARBA:ARBA00088689 ACCEPT leaf (0) 0 human/GTPBP2 GO:1904678 alpha-aminoacyl-tRNA binding ARBA:ARBA00088689 ACCEPT leaf (0) 0 human/GUSB GO:0030214 hyaluronan catabolic process ARBA:ARBA00085621 KEEP_AS_NON_CORE leaf (0) 0 human/GYS2 GO:0061547 glycogen synthase activity, transferring glucose-1-phosphate ARBA:ARBA00091177 ACCEPT leaf (0) 0 human/H3C2 GO:0005654 nucleoplasm ARBA:ARBA00026290 ACCEPT general (21-200) 65 human/HAND2 GO:0003700 DNA-binding transcription factor activity ARBA:ARBA00028295 MODIFY specific (1-20) 16 NEEDS_MORE_SPECIFIC true but uninformative replacement term Correct but less specific than the Pol II-specific term supported by experiments and IBA. human/HAND2 GO:0160108 animal gross anatomical part developmental process ARBA:ARBA00098139 MARK_AS_OVER_ANNOTATED very general (>200 descendants) 3010 TOO_GENERAL true but uninformative Uninformative Uninformative high-level grouping term; specific developmental processes are annotated. human/HAO1 GO:0019395 fatty acid oxidation ARBA:ARBA00027602 MARK_AS_OVER_ANNOTATED specific (1-20) 5 TOO_GENERAL true but uninformative more specific "The enzyme's fatty-acid-related role is the more specific alpha-oxidation of 2-hydroxy fatty acids (separately annotated as GO:0001561 with IDA). The broad ARBA-derived ""fatty acid oxidation"" term is imprecise for this activity." human/HBS1L GO:0010629 negative regulation of gene expression ARBA:ARBA00026647 MARK_AS_OVER_ANNOTATED very general (>200 descendants) 274 INDIRECT_EFFECT overreach indirect Generic and indirect; the mechanistic role is ribosome rescue / no-go and non-stop mRNA decay, not transcriptional/general gene-expression regulation. human/HDAC4 GO:0033558 protein lysine deacetylase activity ARBA:ARBA00028193 ACCEPT specific (1-20) 19 human/HDAC4 GO:0140297 DNA-binding transcription factor binding ARBA:ARBA00026336 ACCEPT specific (1-20) 20 human/HDAC6 GO:0000118 histone deacetylase complex ARBA:ARBA00043644 MARK_AS_OVER_ANNOTATED specific (1-20) 10 UNCLASSIFIED unclassified HDAC6 is predominantly cytoplasmic and deacetylates non-histone substrates. While it can interact with other HDACs, it does not primarily function in canonical nuclear histone deacetylase complexes. This annotation may be misleading about HDAC6's actual role. human/HDAC6 GO:0006950 response to stress ARBA:ARBA00026300 KEEP_AS_NON_CORE very general (>200 descendants) 590 human/HDAC6 GO:0016236 macroautophagy ARBA:ARBA00027245 ACCEPT general (21-200) 34 human/HDAC6 GO:0032886 regulation of microtubule-based process ARBA:ARBA00033541 ACCEPT general (21-200) 100 human/HDAC6 GO:0051129 negative regulation of cellular component organization ARBA:ARBA00026626 KEEP_AS_NON_CORE very general (>200 descendants) 285 human/HDAC6 GO:0051130 positive regulation of cellular component organization ARBA:ARBA00026675 KEEP_AS_NON_CORE very general (>200 descendants) 291 human/HDAC6 GO:0098732 macromolecule deacylation ARBA:ARBA00028610 ACCEPT specific (1-20) 17 human/HDAC6 GO:0120025 plasma membrane bounded cell projection ARBA:ARBA00028036 KEEP_AS_NON_CORE very general (>200 descendants) 303 human/HEXA GO:0008375 acetylglucosaminyltransferase activity ARBA:ARBA00026813 REMOVE general (21-200) 36 WRONG_ACTIVITY wrong manual WRONG_ACTIVITY Wrong enzyme class for an electronic inference; HEXA is a hydrolase, not a glycosyltransferase. This ARBA mapping contradicts the well-established catalytic activity and family assignment. human/HEXA GO:0016042 lipid catabolic process ARBA:ARBA00028909 ACCEPT general (21-200) 154 human/HEXA GO:0042582 azurophil granule ARBA:ARBA00086965 KEEP_AS_NON_CORE specific (1-20) 2 human/HEXA GO:0043202 lysosomal lumen ARBA:ARBA00029034 ACCEPT specific (1-20) 3 human/HEXA GO:1901135 carbohydrate derivative metabolic process ARBA:ARBA00026297 ACCEPT very general (>200 descendants) 637 human/HEXB GO:0008375 acetylglucosaminyltransferase activity ARBA:ARBA00026813 MARK_AS_OVER_ANNOTATED general (21-200) 36 UNCLASSIFIED unclassified Transferase activity is inconsistent with the well-established hydrolase mechanism and fold; this is a mis-typing of the glycosidase activity. Per curation policy the paired experimental IDA is retained but flagged rather than removed. human/HEXB GO:0016042 lipid catabolic process ARBA:ARBA00028909 MARK_AS_OVER_ANNOTATED general (21-200) 154 TOO_GENERAL true but uninformative general Correct in spirit (ganglioside/glycosphingolipid degradation is lipid catabolism) but too general; GO:0006689 is preferred. human/HEXB GO:0042582 azurophil granule ARBA:ARBA00086965 KEEP_AS_NON_CORE specific (1-20) 2 human/HEXB GO:0043202 lysosomal lumen ARBA:ARBA00029034 ACCEPT specific (1-20) 3 human/HEXB GO:1901135 carbohydrate derivative metabolic process ARBA:ARBA00026297 MARK_AS_OVER_ANNOTATED very general (>200 descendants) 637 TOO_GENERAL true but uninformative Uninformative Uninformatively general; specific catabolic BP terms are preferred. human/HK1 GO:0019637 organophosphate metabolic process ARBA:ARBA00028049 KEEP_AS_NON_CORE very general (>200 descendants) 627 human/HK1 GO:1901135 carbohydrate derivative metabolic process ARBA:ARBA00026297 KEEP_AS_NON_CORE very general (>200 descendants) 637 human/HLCS GO:0006768 biotin metabolic process ARBA:ARBA00027971 ACCEPT specific (1-20) 2 human/HMBS GO:0006779 porphyrin-containing compound biosynthetic process ARBA:ARBA00027896 ACCEPT specific (1-20) 16 human/HMGB1 GO:0000793 condensed chromosome ARBA:ARBA00027532 ACCEPT general (21-200) 29 human/HMGB1 GO:0001938 positive regulation of endothelial cell proliferation ARBA:ARBA00091246 KEEP_AS_NON_CORE specific (1-20) 2 human/HMGB1 GO:0003684 damaged DNA binding ARBA:ARBA00089041 ACCEPT specific (1-20) 8 human/HMGB1 GO:0003714 transcription corepressor activity ARBA:ARBA00089152 ACCEPT specific (1-20) 1 human/HMGB1 GO:0006259 DNA metabolic process ARBA:ARBA00028839 ACCEPT very general (>200 descendants) 285 human/HMGB1 GO:0006955 immune response ARBA:ARBA00026313 ACCEPT very general (>200 descendants) 207 human/HMGB1 GO:0008289 lipid binding ARBA:ARBA00027537 ACCEPT general (21-200) 94 human/HMGB1 GO:0010596 negative regulation of endothelial cell migration ARBA:ARBA00092352 KEEP_AS_NON_CORE specific (1-20) 4 human/HMGB1 GO:0032722 positive regulation of chemokine production ARBA:ARBA00085792 ACCEPT specific (1-20) 13 human/HMGB1 GO:0032732 positive regulation of interleukin-1 production ARBA:ARBA00033917 ACCEPT specific (1-20) 2 human/HMGB1 GO:0045597 positive regulation of cell differentiation ARBA:ARBA00028476 KEEP_AS_NON_CORE very general (>200 descendants) 224 human/HMGB1 GO:0048018 receptor ligand activity ARBA:ARBA00028558 ACCEPT general (21-200) 34 human/HMGB1 GO:0048468 cell development ARBA:ARBA00028665 KEEP_AS_NON_CORE very general (>200 descendants) 672 human/HMGB1 GO:0050792 regulation of viral process ARBA:ARBA00091598 ACCEPT general (21-200) 38 human/HMGB1 GO:0051052 regulation of DNA metabolic process ARBA:ARBA00027282 ACCEPT general (21-200) 185 human/HMGB1 GO:1903706 regulation of hemopoiesis ARBA:ARBA00029137 KEEP_AS_NON_CORE general (21-200) 138 human/HMGCL GO:0046951 ketone body biosynthetic process ARBA:ARBA00084707 ACCEPT leaf (0) 0 human/HOGA1 GO:0009436 glyoxylate catabolic process ARBA:ARBA00092669 KEEP_AS_NON_CORE leaf (0) 0 human/HPD GO:0006572 L-tyrosine catabolic process ARBA:ARBA00085483 ACCEPT leaf (0) 0 human/HPD GO:0042803 protein homodimerization activity ARBA:ARBA00027933 ACCEPT leaf (0) 0 human/HPRT1 GO:0046100 hypoxanthine metabolic process ARBA:ARBA00091108 ACCEPT specific (1-20) 3 human/HRAS GO:0000165 MAPK cascade ARBA:ARBA00029221 ACCEPT specific (1-20) 18 human/HSD11B2 GO:0016616 oxidoreductase activity, acting on the CH-OH group of donors, NAD or NADP as acceptor ARBA:ARBA00028442 ACCEPT very general (>200 descendants) 364 human/HSD17B12 GO:0005783 endoplasmic reticulum ARBA:ARBA00028672 MARK_AS_OVER_ANNOTATED general (21-200) 100 TOO_GENERAL true but uninformative Subsumed Subsumed by the more specific ER membrane (GO:0005789) location. human/HSD17B12 GO:0008610 lipid biosynthetic process ARBA:ARBA00027236 MARK_AS_OVER_ANNOTATED very general (>200 descendants) 258 TOO_GENERAL true but uninformative High-level High-level parent of the specific fatty-acid elongation process; the more precise fatty-acid elongation terms are experimentally supported. human/HSD17B12 GO:0016614 oxidoreductase activity, acting on CH-OH group of donors ARBA:ARBA00028437 MARK_AS_OVER_ANNOTATED very general (>200 descendants) 457 TOO_GENERAL true but uninformative Parent Parent term of the experimentally supported GO:0141040; redundant with the specific activity. human/HSD17B3 GO:0008610 lipid biosynthetic process ARBA:ARBA00027236 MARK_AS_OVER_ANNOTATED very general (>200 descendants) 258 TOO_GENERAL true but uninformative already captured The specific role of HSD17B3 is in androgen/testosterone (steroid hormone) biosynthesis, already captured by GO:0006702 and GO:0061370. The generic lipid biosynthetic process term over-generalizes and adds no useful signal. human/HSD17B3 GO:0016614 oxidoreductase activity, acting on CH-OH group of donors ARBA:ARBA00028437 ACCEPT very general (>200 descendants) 457 human/HSD17B4 GO:0006629 lipid metabolic process ARBA:ARBA00028591 MARK_AS_OVER_ANNOTATED very general (>200 descendants) 608 TOO_GENERAL true but uninformative general Electronic ARBA annotation to the very general parent term 'lipid metabolic process'. Not wrong but far less informative than fatty acid beta-oxidation; a high-level grouping term. human/HSD17B4 GO:0016616 oxidoreductase activity, acting on the CH-OH group of donors, NAD or NADP as acceptor ARBA:ARBA00028442 MODIFY very general (>200 descendants) 364 NEEDS_MORE_SPECIFIC true but uninformative replacement term Electronic ARBA annotation to a broad oxidoreductase grouping term. This is a correct but non-specific ancestor of the actual (3R)-3-hydroxyacyl-CoA dehydrogenase (NAD+) activity; the specific term GO:0106386 should be used instead. human/HSD3B2 GO:0006702 androgen biosynthetic process ARBA:ARBA00029222 KEEP_AS_NON_CORE leaf (0) 0 human/HSF1 GO:0000981 DNA-binding transcription factor activity, RNA polymerase II-specific ARBA:ARBA00029016 ACCEPT specific (1-20) 8 human/HSP90AA1 GO:0007004 telomere maintenance via telomerase ARBA:ARBA00091988 KEEP_AS_NON_CORE leaf (0) 0 human/HSP90AA1 GO:0031396 regulation of protein ubiquitination ARBA:ARBA00028313 KEEP_AS_NON_CORE general (21-200) 25 human/HSP90AA1 GO:0031625 ubiquitin protein ligase binding ARBA:ARBA00028807 KEEP_AS_NON_CORE leaf (0) 0 human/HSP90AA1 GO:0034774 secretory granule lumen ARBA:ARBA00085364 KEEP_AS_NON_CORE specific (1-20) 8 human/HSP90AA1 GO:0042826 histone deacetylase binding ARBA:ARBA00088244 KEEP_AS_NON_CORE leaf (0) 0 human/HSP90AA1 GO:0051131 chaperone-mediated protein complex assembly ARBA:ARBA00087767 KEEP_AS_NON_CORE leaf (0) 0 human/HSP90AA1 GO:0070182 DNA polymerase binding ARBA:ARBA00092213 KEEP_AS_NON_CORE leaf (0) 0 human/HSP90AA1 GO:0097718 disordered domain specific binding ARBA:ARBA00090519 KEEP_AS_NON_CORE leaf (0) 0 human/HSP90AA1 GO:1904813 ficolin-1-rich granule lumen ARBA:ARBA00088974 KEEP_AS_NON_CORE leaf (0) 0 human/HSP90AA1 GO:1905323 telomerase holoenzyme complex assembly ARBA:ARBA00087130 KEEP_AS_NON_CORE specific (1-20) 1 human/HSP90AA1 GO:1990565 HSP90-CDC37 chaperone complex ARBA:ARBA00098332 ACCEPT leaf (0) 0 human/HSPA1A GO:0001664 G protein-coupled receptor binding ARBA:ARBA00027676 MARK_AS_OVER_ANNOTATED very general (>200 descendants) 223 UNCLASSIFIED unclassified Hsp70 binds unfolded Pael-R (a GPCR) in the context of chaperone-mediated quality control and CHIP/Parkin-directed ubiquitination (PMID:12150907), not as a functional GPCR binding partner. This is chaperone-substrate interaction, not receptor binding in the signaling sense. human/HSPA1A GO:0005814 centriole ARBA:ARBA00088571 ACCEPT leaf (0) 0 human/HSPA1A GO:0006402 mRNA catabolic process ARBA:ARBA00027180 KEEP_AS_NON_CORE general (21-200) 26 human/HSPA1A GO:0008285 negative regulation of cell population proliferation ARBA:ARBA00027539 MARK_AS_OVER_ANNOTATED general (21-200) 81 UNCLASSIFIED unclassified The negative regulation of cell proliferation requires WT1, with Hsp70 serving as a cofactor (PMID:9553041). This represents a chaperone client effect, not a direct HSPA1A function in proliferation control. human/HSPA1A GO:0016235 aggresome ARBA:ARBA00086955 ACCEPT leaf (0) 0 human/HSPA1A GO:0016607 nuclear speck ARBA:ARBA00043610 ACCEPT specific (1-20) 1 human/HSPA1A GO:0030308 negative regulation of cell growth ARBA:ARBA00087421 MARK_AS_OVER_ANNOTATED general (21-200) 21 UNCLASSIFIED unclassified As with negative regulation of cell proliferation, the cell growth effect is mediated by WT1 with Hsp70 as a chaperone cofactor (PMID:9553041). This is an over-annotation of HSPA1A function. human/HSPA1A GO:0031072 heat shock protein binding ARBA:ARBA00084805 ACCEPT specific (1-20) 3 human/HSPA1A GO:0031397 negative regulation of protein ubiquitination ARBA:ARBA00086279 ACCEPT specific (1-20) 8 human/HSPA1A GO:0031625 ubiquitin protein ligase binding ARBA:ARBA00028807 ACCEPT leaf (0) 0 human/HSPA1A GO:0032757 positive regulation of interleukin-8 production ARBA:ARBA00085873 KEEP_AS_NON_CORE leaf (0) 0 human/HSPA1A GO:0034599 cellular response to oxidative stress ARBA:ARBA00027632 KEEP_AS_NON_CORE general (21-200) 25 human/HSPA1A GO:0042026 protein refolding ARBA:ARBA00043587 ACCEPT leaf (0) 0 human/HSPA1A GO:0042826 histone deacetylase binding ARBA:ARBA00088244 ACCEPT leaf (0) 0 human/HSPA1A GO:0044183 protein folding chaperone ARBA:ARBA00029119 ACCEPT specific (1-20) 1 human/HSPA1A GO:0045648 positive regulation of erythrocyte differentiation ARBA:ARBA00084758 KEEP_AS_NON_CORE leaf (0) 0 human/HSPA1A GO:0046034 ATP metabolic process ARBA:ARBA00027108 MARK_AS_OVER_ANNOTATED general (21-200) 22 TOO_GENERAL true but uninformative broad This broad BP term is less informative than the molecular-function terms describing HSPA1A's ATPase-driven chaperone cycle. human/HSPA1A GO:0048471 perinuclear region of cytoplasm ARBA:ARBA00091589 ACCEPT specific (1-20) 7 human/HSPA1A GO:0050821 protein stabilization ARBA:ARBA00033884 ACCEPT leaf (0) 0 human/HSPA1A GO:0051082 unfolded protein binding ARBA:ARBA00027557 MODIFY leaf (0) 0 OTHER_TERM different term needed replacement term GO:0051082 is now formally obsolete. HSPA1A has genuine protein folding chaperone activity, not merely unfolded protein binding. The protein actively refolds substrates in an ATP-dependent manner, as demonstrated by Hageman et al. (PMID:21231916). The IBA annotation to GO:0044183 already correctly captures this function. This IEA annotation should be modified to GO:0044183 to align with the term obsoletion and to more accurately represent the molecular function. human/HSPA1A GO:0055131 C3HC4-type RING finger domain binding ARBA:ARBA00084342 ACCEPT leaf (0) 0 human/HSPA1A GO:0070370 cellular heat acclimation ARBA:ARBA00085201 ACCEPT leaf (0) 0 human/HSPA1A GO:0070434 positive regulation of nucleotide-binding oligomerization domain containing 2 signaling pathway ARBA:ARBA00085423 KEEP_AS_NON_CORE leaf (0) 0 human/HSPA1A GO:0071383 cellular response to steroid hormone stimulus ARBA:ARBA00092518 KEEP_AS_NON_CORE general (21-200) 25 human/HSPA1A GO:0090063 positive regulation of microtubule nucleation ARBA:ARBA00087613 KEEP_AS_NON_CORE specific (1-20) 1 human/HSPA1A GO:0090084 negative regulation of inclusion body assembly ARBA:ARBA00087599 ACCEPT specific (1-20) 2 human/HSPA1A GO:0140545 ATP-dependent protein disaggregase activity ARBA:ARBA00085990 MARK_AS_OVER_ANNOTATED leaf (0) 0 UNCLASSIFIED unclassified The annotation overextends family-level proteostasis biology and HSPA8-focused evidence to HSPA1A. HSPA1A's accepted core role should remain ATP-dependent folding/refolding and client triage unless direct HSPA1A disaggregase evidence is available. human/HSPA1A GO:1901673 regulation of mitotic spindle assembly ARBA:ARBA00033492 KEEP_AS_NON_CORE specific (1-20) 3 human/HSPA1A GO:1903265 positive regulation of tumor necrosis factor-mediated signaling pathway ARBA:ARBA00090296 KEEP_AS_NON_CORE leaf (0) 0 human/HSPA1A GO:1904813 ficolin-1-rich granule lumen ARBA:ARBA00088974 ACCEPT leaf (0) 0 human/HSPA1A GO:1990904 ribonucleoprotein complex ARBA:ARBA00028648 KEEP_AS_NON_CORE general (21-200) 112 human/HSPA1A GO:2001240 negative regulation of extrinsic apoptotic signaling pathway in absence of ligand ARBA:ARBA00087900 KEEP_AS_NON_CORE leaf (0) 0 human/HSPA1B GO:0001664 G protein-coupled receptor binding ARBA:ARBA00027676 MARK_AS_OVER_ANNOTATED very general (>200 descendants) 223 UNCLASSIFIED unclassified While HSPA1B does bind GPCRs such as Pael-R, this is in the context of chaperone-substrate interaction, not GPCR-specific binding activity. The term implies a specific functional binding to GPCRs as signaling partners. human/HSPA1B GO:0005814 centriole ARBA:ARBA00088571 MARK_AS_OVER_ANNOTATED leaf (0) 0 WRONG_PARALOG wrong paralog Centriole localization is plausible by paralog inference, but the cited experimental evidence is HSPA1A/HSPA6-specific. This should not be accepted as a supported HSPA1B localization without HSPA1B-specific data. human/HSPA1B GO:0006402 mRNA catabolic process ARBA:ARBA00027180 KEEP_AS_NON_CORE general (21-200) 26 human/HSPA1B GO:0008285 negative regulation of cell population proliferation ARBA:ARBA00027539 KEEP_AS_NON_CORE general (21-200) 81 human/HSPA1B GO:0016235 aggresome ARBA:ARBA00086955 ACCEPT leaf (0) 0 human/HSPA1B GO:0016607 nuclear speck ARBA:ARBA00043610 KEEP_AS_NON_CORE specific (1-20) 1 human/HSPA1B GO:0030308 negative regulation of cell growth ARBA:ARBA00087421 KEEP_AS_NON_CORE general (21-200) 21 human/HSPA1B GO:0031072 heat shock protein binding ARBA:ARBA00084805 ACCEPT specific (1-20) 3 human/HSPA1B GO:0031397 negative regulation of protein ubiquitination ARBA:ARBA00086279 KEEP_AS_NON_CORE specific (1-20) 8 human/HSPA1B GO:0031625 ubiquitin protein ligase binding ARBA:ARBA00028807 ACCEPT leaf (0) 0 human/HSPA1B GO:0032757 positive regulation of interleukin-8 production ARBA:ARBA00085873 KEEP_AS_NON_CORE leaf (0) 0 human/HSPA1B GO:0034599 cellular response to oxidative stress ARBA:ARBA00027632 KEEP_AS_NON_CORE general (21-200) 25 human/HSPA1B GO:0042026 protein refolding ARBA:ARBA00043587 ACCEPT leaf (0) 0 human/HSPA1B GO:0042826 histone deacetylase binding ARBA:ARBA00088244 ACCEPT leaf (0) 0 human/HSPA1B GO:0044183 protein folding chaperone ARBA:ARBA00029119 ACCEPT specific (1-20) 1 human/HSPA1B GO:0045648 positive regulation of erythrocyte differentiation ARBA:ARBA00084758 KEEP_AS_NON_CORE leaf (0) 0 human/HSPA1B GO:0046034 ATP metabolic process ARBA:ARBA00027108 MARK_AS_OVER_ANNOTATED general (21-200) 22 TOO_GENERAL true but uninformative broad This broad BP term is less informative than the molecular-function terms describing HSPA1B's ATPase-driven chaperone cycle. human/HSPA1B GO:0048471 perinuclear region of cytoplasm ARBA:ARBA00091589 ACCEPT specific (1-20) 7 human/HSPA1B GO:0050821 protein stabilization ARBA:ARBA00033884 ACCEPT leaf (0) 0 human/HSPA1B GO:0051082 unfolded protein binding ARBA:ARBA00027557 MODIFY leaf (0) 0 OTHER_TERM different term needed replacement term GO:0051082 is now formally obsolete. HSPA1B does not merely bind unfolded proteins passively; it is an active ATP-dependent protein folding chaperone. The replacement term GO:0044183 (protein folding chaperone) accurately captures the molecular function and is already annotated to HSPA1B via IBA (GO_REF:0000033) and IDA (PMID:15603737) evidence. human/HSPA1B GO:0055131 C3HC4-type RING finger domain binding ARBA:ARBA00084342 ACCEPT leaf (0) 0 human/HSPA1B GO:0070370 cellular heat acclimation ARBA:ARBA00085201 KEEP_AS_NON_CORE leaf (0) 0 human/HSPA1B GO:0070434 positive regulation of nucleotide-binding oligomerization domain containing 2 signaling pathway ARBA:ARBA00085423 KEEP_AS_NON_CORE leaf (0) 0 human/HSPA1B GO:0071383 cellular response to steroid hormone stimulus ARBA:ARBA00092518 KEEP_AS_NON_CORE general (21-200) 25 human/HSPA1B GO:0090063 positive regulation of microtubule nucleation ARBA:ARBA00087613 KEEP_AS_NON_CORE specific (1-20) 1 human/HSPA1B GO:0090084 negative regulation of inclusion body assembly ARBA:ARBA00087599 ACCEPT specific (1-20) 2 human/HSPA1B GO:0140545 ATP-dependent protein disaggregase activity ARBA:ARBA00085990 MARK_AS_OVER_ANNOTATED leaf (0) 0 UNCLASSIFIED unclassified This overextends family-level disaggregation biology and HSPA8-focused evidence to HSPA1B. HSPA1B's core role should be represented as ATP-dependent folding/refolding unless direct HSPA1B disaggregase evidence is available. human/HSPA1B GO:1901673 regulation of mitotic spindle assembly ARBA:ARBA00033492 KEEP_AS_NON_CORE specific (1-20) 3 human/HSPA1B GO:1903265 positive regulation of tumor necrosis factor-mediated signaling pathway ARBA:ARBA00090296 KEEP_AS_NON_CORE leaf (0) 0 human/HSPA1B GO:1904813 ficolin-1-rich granule lumen ARBA:ARBA00088974 KEEP_AS_NON_CORE leaf (0) 0 human/HSPA1B GO:1990904 ribonucleoprotein complex ARBA:ARBA00028648 ACCEPT general (21-200) 112 human/HSPA1B GO:2001240 negative regulation of extrinsic apoptotic signaling pathway in absence of ligand ARBA:ARBA00087900 KEEP_AS_NON_CORE leaf (0) 0 human/HSPA1L GO:0006950 response to stress ARBA:ARBA00026300 KEEP_AS_NON_CORE very general (>200 descendants) 590 human/HSPA1L GO:0031072 heat shock protein binding ARBA:ARBA00084805 ACCEPT specific (1-20) 3 human/HSPA1L GO:0031625 ubiquitin protein ligase binding ARBA:ARBA00028807 ACCEPT leaf (0) 0 human/HSPA1L GO:0042026 protein refolding ARBA:ARBA00043587 ACCEPT leaf (0) 0 human/HSPA1L GO:0051082 unfolded protein binding ARBA:ARBA00027557 MODIFY leaf (0) 0 OTHER_TERM different term needed replacement term GO:0051082 is now formally obsolete. The term conflates passive binding with the active chaperone function that HSP70 family members perform. HSPA1L is an ATP-dependent foldase that undergoes conformational cycling between ATP-bound (low substrate affinity) and ADP-bound (high substrate affinity) states to actively fold client proteins (UniProt P34931). The replacement term GO:0044183 (protein folding chaperone) accurately captures this molecular function. This IEA annotation is redundant with existing IBA and IEA annotations to GO:0044183 and GO:0140662 respectively. human/HSPA2 GO:0006986 response to unfolded protein ARBA:ARBA00086617 ACCEPT specific (1-20) 7 human/HSPA2 GO:0019899 enzyme binding ARBA:ARBA00026481 KEEP_AS_NON_CORE general (21-200) 77 human/HSPA2 GO:0042026 protein refolding ARBA:ARBA00043587 ACCEPT leaf (0) 0 human/HSPA2 GO:0051082 unfolded protein binding ARBA:ARBA00027557 MODIFY leaf (0) 0 OTHER_TERM different term needed replacement term "GO:0051082 is now formally obsolete per go-ontology#30962 because it conflates passive binding with active chaperone function. For HSP70 family members like HSPA2, the correct term is GO:0044183 ""protein folding chaperone"" (foldase), as the protein actively assists protein folding through ATP-dependent cycles. This IEA annotation should be replaced with the correct MF term." human/HSPA4 GO:0043226 organelle ARBA:ARBA00029065 KEEP_AS_NON_CORE very general (>200 descendants) 1881 human/HSPA5 GO:0019899 enzyme binding ARBA:ARBA00026481 REMOVE general (21-200) 77 ROLE_CONFUSION wrong manual ROLE_CONFUSION Enzyme binding is uninformative; HSPA5 is the substrate of these enzymes rather than having a binding function of its own. human/HSPA6 GO:0006986 response to unfolded protein ARBA:ARBA00086617 ACCEPT specific (1-20) 7 human/HSPA6 GO:0019899 enzyme binding ARBA:ARBA00026481 KEEP_AS_NON_CORE general (21-200) 77 human/HSPA6 GO:0042026 protein refolding ARBA:ARBA00043587 ACCEPT leaf (0) 0 human/HSPA6 GO:0051082 unfolded protein binding ARBA:ARBA00027557 MODIFY leaf (0) 0 OTHER_TERM different term needed replacement term GO:0051082 (unfolded protein binding) is scheduled for obsolescence (go-ontology#30962). HSPA6 functions as an ATP-dependent protein folding chaperone, not merely a passive binder of unfolded proteins. The ARBA-predicted annotation should be replaced with GO:0044183 (protein folding chaperone), consistent with the experimentally validated IDA evidence from PMID:21231916 showing HSPA6 assists in reactivation of heat-unfolded p53, and with the existing IBA annotation for GO:0044183. human/HSPA8 GO:0001664 G protein-coupled receptor binding ARBA:ARBA00027676 MARK_AS_OVER_ANNOTATED very general (>200 descendants) 223 TOO_GENERAL true but uninformative general GPCR binding is not a core HSPA8 function. The accessible Pael-R/GPR37 evidence supports a chaperone-client quality-control interaction rather than a general GPCR-binding role, so this IEA term overstates the biological meaning of the interaction. human/HSPA8 GO:0009968 negative regulation of signal transduction ARBA:ARBA00027208 KEEP_AS_NON_CORE very general (>200 descendants) 244 human/HSPA8 GO:0031072 heat shock protein binding ARBA:ARBA00084805 ACCEPT specific (1-20) 3 human/HSPA8 GO:0031625 ubiquitin protein ligase binding ARBA:ARBA00028807 ACCEPT leaf (0) 0 human/HSPA8 GO:0031647 regulation of protein stability ARBA:ARBA00033870 ACCEPT specific (1-20) 2 human/HSPA8 GO:0033554 cellular response to stress ARBA:ARBA00028184 ACCEPT very general (>200 descendants) 285 human/HSPA8 GO:0039531 regulation of cytoplasmic pattern recognition receptor signaling pathway ARBA:ARBA00089228 KEEP_AS_NON_CORE general (21-200) 50 human/HSPA8 GO:0042026 protein refolding ARBA:ARBA00043587 ACCEPT leaf (0) 0 human/HSPA8 GO:0043254 regulation of protein-containing complex assembly ARBA:ARBA00086482 ACCEPT general (21-200) 132 human/HSPA8 GO:0046034 ATP metabolic process ARBA:ARBA00027108 MARK_AS_OVER_ANNOTATED general (21-200) 22 TOO_GENERAL true but uninformative broad This broad BP parent is less informative than the molecular-function terms that describe HSPA8's ATPase-driven chaperone cycle. human/HSPA8 GO:0051082 unfolded protein binding ARBA:ARBA00027557 MODIFY leaf (0) 0 OTHER_TERM different term needed replacement term GO:0051082 is now formally obsolete as part of the unfolded protein binding obsoletion project. The correct replacement for HSPA8 is GO:0044183 (protein folding chaperone) since HSPA8/HSC70 binds client polypeptides to assist their folding, not merely to bind unfolded proteins. More specifically, GO:0140662 (ATP-dependent protein folding chaperone) is the most appropriate term. human/HSPA8 GO:0051129 negative regulation of cellular component organization ARBA:ARBA00026626 KEEP_AS_NON_CORE very general (>200 descendants) 285 human/HSPA8 GO:0055131 C3HC4-type RING finger domain binding ARBA:ARBA00084342 ACCEPT leaf (0) 0 human/HSPA8 GO:0071383 cellular response to steroid hormone stimulus ARBA:ARBA00092518 KEEP_AS_NON_CORE general (21-200) 25 human/HSPA8 GO:0072318 clathrin coat disassembly ARBA:ARBA00044585 ACCEPT specific (1-20) 2 human/HSPA8 GO:0140545 ATP-dependent protein disaggregase activity ARBA:ARBA00085990 ACCEPT leaf (0) 0 human/HSPA8 GO:1902903 regulation of supramolecular fiber organization ARBA:ARBA00026728 KEEP_AS_NON_CORE general (21-200) 66 human/HSPA8 GO:1904813 ficolin-1-rich granule lumen ARBA:ARBA00088974 KEEP_AS_NON_CORE leaf (0) 0 human/HSPA8 GO:1990904 ribonucleoprotein complex ARBA:ARBA00028648 ACCEPT general (21-200) 112 human/HSPD1 GO:0001819 positive regulation of cytokine production ARBA:ARBA00028861 KEEP_AS_NON_CORE general (21-200) 86 human/HSPG2 GO:0005796 Golgi lumen ARBA:ARBA00028705 KEEP_AS_NON_CORE specific (1-20) 2 human/HSPG2 GO:0007420 brain development ARBA:ARBA00026443 ACCEPT very general (>200 descendants) 353 human/HSPG2 GO:0030154 cell differentiation ARBA:ARBA00027429 KEEP_AS_NON_CORE very general (>200 descendants) 1345 human/HSPG2 GO:0072359 circulatory system development ARBA:ARBA00027039 ACCEPT very general (>200 descendants) 399 human/HTT GO:0007017 microtubule-based process ARBA:ARBA00026739 MARK_AS_OVER_ANNOTATED very general (>200 descendants) 206 TOO_GENERAL true but uninformative Parent Parent term is too general given the available specific microtubule-based process annotations for HTT in the same review. human/HTT GO:0009966 regulation of signal transduction ARBA:ARBA00027204 MARK_AS_OVER_ANNOTATED very general (>200 descendants) 696 TOO_GENERAL true but uninformative generic Too generic to add curatorial value; HTT does not have a defined signal transduction activity, only context-specific pathway-modulating interactions. human/HTT GO:0030424 axon ARBA:ARBA00028032 ACCEPT general (21-200) 59 human/HTT GO:0043066 negative regulation of apoptotic process ARBA:ARBA00027746 KEEP_AS_NON_CORE general (21-200) 79 human/HTT GO:0045202 synapse ARBA:ARBA00027462 KEEP_AS_NON_CORE general (21-200) 142 human/ICA1 GO:0005737 cytoplasm ARBA:ARBA00026971 ACCEPT very general (>200 descendants) 1146 human/ICA1 GO:0012505 endomembrane system ARBA:ARBA00028953 ACCEPT very general (>200 descendants) 357 human/ICA1L GO:0005737 cytoplasm ARBA:ARBA00026971 ACCEPT very general (>200 descendants) 1146 human/ICA1L GO:0012505 endomembrane system ARBA:ARBA00028953 ACCEPT very general (>200 descendants) 357 human/IDI1 GO:0016860 intramolecular oxidoreductase activity ARBA:ARBA00026964 MODIFY general (21-200) 67 NEEDS_MORE_SPECIFIC true but uninformative replacement term Correct but overly general; the specific, experimentally established activity is isopentenyl-diphosphate delta-isomerase activity (GO:0004452). human/IDI2 GO:0016860 intramolecular oxidoreductase activity ARBA:ARBA00026964 MODIFY general (21-200) 67 NEEDS_MORE_SPECIFIC true but uninformative replacement term Correct but overly general; the specific, experimentally established activity is isopentenyl-diphosphate delta-isomerase activity (GO:0004452). human/IDS GO:0043202 lysosomal lumen ARBA:ARBA00029034 ACCEPT specific (1-20) 3 human/IDS GO:1901136 carbohydrate derivative catabolic process ARBA:ARBA00026295 MARK_AS_OVER_ANNOTATED general (21-200) 156 TOO_GENERAL true but uninformative uninformative Correct in essence but uninformatively general. The informative process terms for IDS are glycosaminoglycan catabolic process (GO:0006027, already annotated by IDA) and the heparan/dermatan sulfate catabolic subprocesses. Kept but flagged as over-general rather than removed, since it is a true (electronic) superclass. human/IDUA GO:0030200 heparan sulfate proteoglycan catabolic process ARBA:ARBA00085487 ACCEPT leaf (0) 0 human/IDUA GO:0030209 dermatan sulfate proteoglycan catabolic process ARBA:ARBA00085492 ACCEPT leaf (0) 0 human/IDUA GO:0030211 heparin proteoglycan catabolic process ARBA:ARBA00085613 ACCEPT leaf (0) 0 human/IDUA GO:0043202 lysosomal lumen ARBA:ARBA00029034 ACCEPT specific (1-20) 3 human/IFI16 GO:0005730 nucleolus ARBA:ARBA00026953 ACCEPT general (21-200) 24 human/IFIH1 GO:0007165 signal transduction ARBA:ARBA00029050 MODIFY very general (>200 descendants) 937 NEEDS_MORE_SPECIFIC true but uninformative replacement term Correct but far too general; the specific pathway this protein initiates is already annotated. human/IFIH1 GO:0051259 protein complex oligomerization ARBA:ARBA00043446 ACCEPT specific (1-20) 9 human/IFIH1 GO:0140374 antiviral innate immune response ARBA:ARBA00086315 ACCEPT leaf (0) 0 human/IFT122 GO:0030991 intraciliary transport particle A ARBA:ARBA00087944 ACCEPT leaf (0) 0 human/IFT122 GO:0035720 intraciliary anterograde transport ARBA:ARBA00098463 ACCEPT leaf (0) 0 human/IFT122 GO:0035869 ciliary transition zone ARBA:ARBA00092392 ACCEPT specific (1-20) 8 human/IFT122 GO:0036064 ciliary basal body ARBA:ARBA00044605 ACCEPT specific (1-20) 9 human/IFT122 GO:0061512 protein localization to cilium ARBA:ARBA00091714 ACCEPT specific (1-20) 8 human/IFT140 GO:0035721 intraciliary retrograde transport ARBA:ARBA00092633 ACCEPT leaf (0) 0 human/IFT140 GO:0060271 cilium assembly ARBA:ARBA00027837 ACCEPT specific (1-20) 19 human/IFT172 GO:0030990 intraciliary transport particle ARBA:ARBA00050083 ACCEPT specific (1-20) 2 human/IFT172 GO:0044782 cilium organization ARBA:ARBA00027540 ACCEPT general (21-200) 28 human/IFT81 GO:0005815 microtubule organizing center ARBA:ARBA00029135 KEEP_AS_NON_CORE general (21-200) 42 human/IFT81 GO:0007018 microtubule-based movement ARBA:ARBA00033543 ACCEPT general (21-200) 84 human/IFT88 GO:0030992 intraciliary transport particle B ARBA:ARBA00087941 ACCEPT leaf (0) 0 human/IFT88 GO:0036064 ciliary basal body ARBA:ARBA00044605 ACCEPT specific (1-20) 9 human/IFT88 GO:0097542 ciliary tip ARBA:ARBA00044587 ACCEPT leaf (0) 0 human/IFT88 GO:1902017 regulation of cilium assembly ARBA:ARBA00088688 MODIFY specific (1-20) 8 TOO_SPECIFIC overreach replacement term Cilium assembly (GO:0060271) is the more accurate representation of IFT88's direct role. human/IGFBP3 GO:0014912 negative regulation of smooth muscle cell migration ARBA:ARBA00089843 KEEP_AS_NON_CORE specific (1-20) 2 human/IGFBP3 GO:0031994 insulin-like growth factor I binding ARBA:ARBA00086756 ACCEPT leaf (0) 0 human/IGFBP3 GO:0042567 insulin-like growth factor ternary complex ARBA:ARBA00086941 ACCEPT leaf (0) 0 human/IGFBP3 GO:0048662 negative regulation of smooth muscle cell proliferation ARBA:ARBA00091356 KEEP_AS_NON_CORE specific (1-20) 1 human/IGFBP5 GO:0005788 endoplasmic reticulum lumen ARBA:ARBA00028691 KEEP_AS_NON_CORE specific (1-20) 9 human/IGFBP5 GO:0014912 negative regulation of smooth muscle cell migration ARBA:ARBA00089843 KEEP_AS_NON_CORE specific (1-20) 2 human/IGFBP5 GO:0031994 insulin-like growth factor I binding ARBA:ARBA00086756 ACCEPT leaf (0) 0 human/IGFBP5 GO:0042567 insulin-like growth factor ternary complex ARBA:ARBA00086941 ACCEPT leaf (0) 0 human/IGFBP5 GO:0048662 negative regulation of smooth muscle cell proliferation ARBA:ARBA00091356 KEEP_AS_NON_CORE specific (1-20) 1 human/IGFBP5 GO:0140144 non-collagenous component of basement membrane ARBA:ARBA00096893 KEEP_AS_NON_CORE specific (1-20) 18 human/IKZF1 GO:0007498 mesoderm development ARBA:ARBA00084318 MARK_AS_OVER_ANNOTATED general (21-200) 51 TOO_GENERAL true but uninformative broad While hematopoietic cells are mesodermal derivatives, annotating Ikaros to mesoderm development is over-annotation. Ikaros functions specifically in hematopoietic and lymphoid lineage commitment and differentiation, not in broad mesoderm specification. The ARBA model likely inferred this from the association of lymphoid development with mesodermal lineage, but the annotation is too general and misleading for Ikaros's actual role. human/IKZF1 GO:0030098 lymphocyte differentiation ARBA:ARBA00086298 ACCEPT general (21-200) 93 human/IL13 GO:0042116 macrophage activation ARBA:ARBA00085939 ACCEPT specific (1-20) 3 human/IL15 GO:0008284 positive regulation of cell population proliferation ARBA:ARBA00027538 KEEP_AS_NON_CORE general (21-200) 85 human/IL21 GO:0001819 positive regulation of cytokine production ARBA:ARBA00028861 ACCEPT general (21-200) 86 human/IL21 GO:0006952 defense response ARBA:ARBA00026315 MARK_AS_OVER_ANNOTATED general (21-200) 175 TOO_GENERAL true but uninformative general Very general term. IL21 does participate in immune defense but more specific terms (defense response to virus) are available. Term is too general for core function. human/IL21 GO:0009615 response to virus ARBA:ARBA00026492 KEEP_AS_NON_CORE specific (1-20) 9 human/IL21 GO:0045954 positive regulation of natural killer cell mediated cytotoxicity ARBA:ARBA00086062 KEEP_AS_NON_CORE specific (1-20) 3 human/IL21 GO:0048468 cell development ARBA:ARBA00028665 MARK_AS_OVER_ANNOTATED very general (>200 descendants) 672 TOO_GENERAL true but uninformative general Very general term. IL21 is involved in specific cell development processes (NK cell, B cell, Tfh cell development) but this term is too broad. More specific terms should be used. human/IL21 GO:0051251 positive regulation of lymphocyte activation ARBA:ARBA00028920 KEEP_AS_NON_CORE general (21-200) 64 human/IL2RA GO:0002682 regulation of immune system process ARBA:ARBA00027003 ACCEPT very general (>200 descendants) 1028 human/IL2RA GO:0005886 plasma membrane ARBA:ARBA00027801 ACCEPT very general (>200 descendants) 415 human/IL2RA GO:0006915 apoptotic process ARBA:ARBA00027755 MARK_AS_OVER_ANNOTATED general (21-200) 115 INDIRECT_EFFECT overreach indirect IL2RA does not directly regulate apoptosis. The connection is indirect: IL-2 signaling promotes survival via STAT5/bcl-2, and its withdrawal can lead to apoptosis. The CD25-deficient patient thymocytes showed altered bcl-2 levels (PMID:9096364), but this is a downstream consequence of impaired IL-2 signaling, not a direct function of IL2RA. This is an over-annotation of a pleiotropic downstream effect. human/IL2RA GO:0006955 immune response ARBA:ARBA00026313 ACCEPT very general (>200 descendants) 207 human/IL4 GO:0010628 positive regulation of gene expression ARBA:ARBA00026655 ACCEPT general (21-200) 198 human/IL4 GO:0030335 positive regulation of cell migration ARBA:ARBA00028907 KEEP_AS_NON_CORE general (21-200) 68 human/IL4 GO:0045321 leukocyte activation ARBA:ARBA00091994 ACCEPT general (21-200) 181 human/IL4 GO:0051239 regulation of multicellular organismal process ARBA:ARBA00028859 MARK_AS_OVER_ANNOTATED very general (>200 descendants) 1807 TOO_GENERAL true but uninformative broad This is an extremely broad and uninformative term. While technically true, it provides no useful information about IL-4 function. More specific terms are available and annotated. The ARBA machine learning annotation is too general to be informative. human/IL4 GO:0080090 regulation of primary metabolic process ARBA:ARBA00026284 MARK_AS_OVER_ANNOTATED very general (>200 descendants) 1424 TOO_GENERAL true but uninformative general This term is far too general to be informative for IL-4 annotation. While IL-4 signaling does affect metabolic processes in target cells, this ARBA-generated term does not convey any meaningful biological insight about the protein. human/IL4I1 GO:0002841 negative regulation of T cell mediated immune response to tumor cell ARBA:ARBA00090130 ACCEPT specific (1-20) 2 human/IL4I1 GO:0005737 cytoplasm ARBA:ARBA00026971 MARK_AS_OVER_ANNOTATED very general (>200 descendants) 1146 UNCLASSIFIED unclassified This ARBA annotation may reflect transient cytoplasmic presence during secretory pathway transit rather than functional localization. IL4I1 is a secreted protein with a signal peptide. The more relevant localizations are extracellular region, lysosome, and acrosomal vesicle. human/IL4I1 GO:0009072 aromatic amino acid metabolic process ARBA:ARBA00028533 ACCEPT specific (1-20) 18 human/IL4I1 GO:0045591 positive regulation of regulatory T cell differentiation ARBA:ARBA00085187 ACCEPT specific (1-20) 1 human/IL7R GO:0019221 cytokine-mediated signaling pathway ARBA:ARBA00028236 ACCEPT general (21-200) 120 human/ILK GO:0009653 anatomical structure morphogenesis ARBA:ARBA00026583 KEEP_AS_NON_CORE very general (>200 descendants) 1501 human/INPP5D GO:0006661 phosphatidylinositol biosynthetic process ARBA:ARBA00028655 MODIFY leaf (0) 0 OTHER_TERM different term needed replacement term Replace phosphatidylinositol biosynthetic process with phosphatidylinositol dephosphorylation for INPP5D phosphatase biology. human/INPP5E GO:0019637 organophosphate metabolic process ARBA:ARBA00028049 ACCEPT very general (>200 descendants) 627 human/INPP5E GO:0034594 phosphatidylinositol trisphosphate phosphatase activity ARBA:ARBA00092429 ACCEPT specific (1-20) 3 human/INPP5E GO:0120025 plasma membrane bounded cell projection ARBA:ARBA00028036 ACCEPT very general (>200 descendants) 303 human/INS GO:1901701 cellular response to oxygen-containing compound ARBA:ARBA00027483 MARK_AS_OVER_ANNOTATED very general (>200 descendants) 308 TOO_GENERAL true but uninformative general This term is far too general and non-specific to be useful for insulin annotation. While technically insulin signaling may involve responses to oxygen-containing compounds, this annotation doesn't capture any meaningful aspect of insulin's specific biological role. This represents computational over-annotation from ARBA. human/IP6K3 GO:0000827 inositol-1,3,4,5,6-pentakisphosphate kinase activity ARBA:ARBA00090538 ACCEPT leaf (0) 0 human/IP6K3 GO:0000828 inositol hexakisphosphate kinase activity ARBA:ARBA00026663 ACCEPT specific (1-20) 5 human/IP6K3 GO:0000829 diphosphoinositol pentakisphosphate kinase activity ARBA:ARBA00047220 ACCEPT specific (1-20) 4 human/IP6K3 GO:0043647 inositol phosphate metabolic process ARBA:ARBA00087379 ACCEPT specific (1-20) 7 human/IP6K3 GO:0046488 phosphatidylinositol metabolic process ARBA:ARBA00028373 MODIFY specific (1-20) 4 OTHER_TERM different term needed replacement term IP6K3 is not primarily a phosphatidylinositol lipid kinase. The supported biological process is soluble inositol phosphate biosynthesis/metabolism. human/IP6K3 GO:0052836 inositol 5-diphosphate pentakisphosphate 5-kinase activity ARBA:ARBA00088636 ACCEPT leaf (0) 0 human/IP6K3 GO:0052839 diphosphoinositol tetrakisphosphate kinase activity ARBA:ARBA00088640 ACCEPT leaf (0) 0 human/IP6K3 GO:0090407 organophosphate biosynthetic process ARBA:ARBA00029048 MARK_AS_OVER_ANNOTATED very general (>200 descendants) 274 TOO_GENERAL true but uninformative more informative The more informative process is soluble inositol phosphate/pyrophosphate biosynthesis. This broad parent term obscures the pathway specificity. human/IRAK3 GO:0001960 negative regulation of cytokine-mediated signaling pathway ARBA:ARBA00091266 ACCEPT general (21-200) 21 human/IRAK3 GO:0002684 positive regulation of immune system process ARBA:ARBA00027011 KEEP_AS_NON_CORE very general (>200 descendants) 392 human/IRAK3 GO:0009615 response to virus ARBA:ARBA00026492 UNDECIDED specific (1-20) 9 human/IRAK3 GO:0043122 regulation of canonical NF-kappaB signal transduction ARBA:ARBA00026688 ACCEPT specific (1-20) 2 human/IRAK3 GO:0045088 regulation of innate immune response ARBA:ARBA00027944 ACCEPT very general (>200 descendants) 201 human/IRAK3 GO:0070498 interleukin-1-mediated signaling pathway ARBA:ARBA00084869 ACCEPT specific (1-20) 1 human/IRF3 GO:0045944 positive regulation of transcription by RNA polymerase II ARBA:ARBA00027996 ACCEPT specific (1-20) 12 human/IRF4 GO:0000978 RNA polymerase II cis-regulatory region sequence-specific DNA binding ARBA:ARBA00028975 ACCEPT specific (1-20) 12 human/IRF4 GO:0045944 positive regulation of transcription by RNA polymerase II ARBA:ARBA00027996 ACCEPT specific (1-20) 12 human/IRF4 GO:0051240 positive regulation of multicellular organismal process ARBA:ARBA00028891 MARK_AS_OVER_ANNOTATED very general (>200 descendants) 565 TOO_GENERAL true but uninformative broad This term is extremely broad and uninformative. While IRF4 does participate in processes that positively regulate multicellular organismal processes (e.g., immune cell differentiation), this annotation is too vague to be useful. More specific terms like regulation of T-helper cell differentiation or plasma cell differentiation are far more informative. human/IRF8 GO:0000978 RNA polymerase II cis-regulatory region sequence-specific DNA binding ARBA:ARBA00028975 ACCEPT specific (1-20) 12 human/IRF8 GO:0006955 immune response ARBA:ARBA00026313 ACCEPT very general (>200 descendants) 207 human/IRF8 GO:0098542 defense response to other organism ARBA:ARBA00027395 KEEP_AS_NON_CORE general (21-200) 77 human/ISCA2 GO:0120510 mitochondrial [4Fe-4S] assembly complex ARBA:ARBA00091107 ACCEPT leaf (0) 0 human/ITGB1 GO:0001525 angiogenesis ARBA:ARBA00090097 KEEP_AS_NON_CORE specific (1-20) 17 human/ITGB1 GO:0001726 ruffle ARBA:ARBA00089602 KEEP_AS_NON_CORE specific (1-20) 1 human/ITGB1 GO:0001968 fibronectin binding ARBA:ARBA00091264 ACCEPT leaf (0) 0 human/ITGB1 GO:0002020 protease binding ARBA:ARBA00087861 KEEP_AS_NON_CORE specific (1-20) 2 human/ITGB1 GO:0007160 cell-matrix adhesion ARBA:ARBA00085356 ACCEPT specific (1-20) 12 human/ITGB1 GO:0007229 integrin-mediated signaling pathway ARBA:ARBA00084939 ACCEPT leaf (0) 0 human/ITGB1 GO:0015026 coreceptor activity ARBA:ARBA00026504 KEEP_AS_NON_CORE leaf (0) 0 human/ITGB1 GO:0030175 filopodium ARBA:ARBA00085970 KEEP_AS_NON_CORE specific (1-20) 5 human/ITGB1 GO:0034113 heterotypic cell-cell adhesion ARBA:ARBA00090976 KEEP_AS_NON_CORE specific (1-20) 6 human/ITGB1 GO:0044877 protein-containing complex binding ARBA:ARBA00026521 MARK_AS_OVER_ANNOTATED general (21-200) 108 TOO_GENERAL true but uninformative generic ARBA prediction of protein-containing complex binding; too generic to be informative for beta1, whose specific binding activities are captured elsewhere. human/ITGB1 GO:0048333 mesodermal cell differentiation ARBA:ARBA00089498 MARK_AS_OVER_ANNOTATED specific (1-20) 20 NO_EVIDENCE overreach no evidence ARBA prediction of mesodermal cell differentiation; no evidence that beta1 performs a step of mesoderm differentiation. human/ITGB1 GO:0048468 cell development ARBA:ARBA00028665 MARK_AS_OVER_ANNOTATED very general (>200 descendants) 672 TOO_GENERAL true but uninformative general ARBA prediction of 'cell development' is too general to be informative for beta1. human/ITGB1 GO:0050793 regulation of developmental process ARBA:ARBA00028689 MARK_AS_OVER_ANNOTATED very general (>200 descendants) 1542 TOO_GENERAL true but uninformative general ARBA prediction of 'regulation of developmental process' is too general to be informative. human/ITGB1 GO:0050839 cell adhesion molecule binding ARBA:ARBA00091792 KEEP_AS_NON_CORE specific (1-20) 14 human/ITGB1 GO:1900748 positive regulation of vascular endothelial growth factor signaling pathway ARBA:ARBA00085719 KEEP_AS_NON_CORE leaf (0) 0 human/ITK GO:0005829 cytosol ARBA:ARBA00029243 ACCEPT general (21-200) 73 human/ITK GO:0007165 signal transduction ARBA:ARBA00029050 ACCEPT very general (>200 descendants) 937 human/ITK GO:0042110 T cell activation ARBA:ARBA00085932 KEEP_AS_NON_CORE general (21-200) 87 human/IVD GO:0005739 mitochondrion ARBA:ARBA00026962 ACCEPT general (21-200) 70 human/JAG1 GO:0010468 regulation of gene expression ARBA:ARBA00028334 MARK_AS_OVER_ANNOTATED very general (>200 descendants) 874 INDIRECT_EFFECT overreach Indirect Indirect consequence of Notch signaling in the receiving cell. human/JAG1 GO:0045596 negative regulation of cell differentiation ARBA:ARBA00033859 KEEP_AS_NON_CORE very general (>200 descendants) 252 human/JAG1 GO:0048513 animal organ development ARBA:ARBA00029247 KEEP_AS_NON_CORE very general (>200 descendants) 1888 human/JAG1 GO:0048731 system development ARBA:ARBA00027702 KEEP_AS_NON_CORE very general (>200 descendants) 2438 human/JAK1 GO:0022407 regulation of cell-cell adhesion ARBA:ARBA00028251 KEEP_AS_NON_CORE general (21-200) 158 human/JAK1 GO:0007259 cell surface receptor signaling pathway via JAK-STAT ARBA:ARBA00034574 ACCEPT specific (1-20) 1 human/JAK1 GO:0019221 cytokine-mediated signaling pathway ARBA:ARBA00028236 ACCEPT general (21-200) 120 human/JAK1 GO:0005768 endosome ARBA:ARBA00028568 KEEP_AS_NON_CORE general (21-200) 68 human/JAK1 GO:0031234 extrinsic component of cytoplasmic side of plasma membrane ARBA:ARBA00028967 ACCEPT specific (1-20) 2 human/JAK1 GO:0051239 regulation of multicellular organismal process ARBA:ARBA00028859 MARK_AS_OVER_ANNOTATED very general (>200 descendants) 1807 TOO_GENERAL true but uninformative grouping This grouping term is far too general to convey JAK1's specific role; its cytokine/JAK-STAT signaling functions are captured by more specific terms. Electronic inference only. human/JAK1 GO:0098761 cellular response to interleukin-7 ARBA:ARBA00091517 KEEP_AS_NON_CORE specific (1-20) 2 human/KCNRG GO:0042802 identical protein binding ARBA:ARBA00027930 ACCEPT specific (1-20) 1 human/KCTD10 GO:0006511 ubiquitin-dependent protein catabolic process ARBA:ARBA00026385 ACCEPT specific (1-20) 18 human/KCTD11 GO:0042802 identical protein binding ARBA:ARBA00027930 KEEP_AS_NON_CORE specific (1-20) 1 human/KCTD12 GO:0042802 identical protein binding ARBA:ARBA00027930 ACCEPT specific (1-20) 1 human/KCTD16 GO:0042802 identical protein binding ARBA:ARBA00027930 ACCEPT specific (1-20) 1 human/KCTD18 GO:0042802 identical protein binding ARBA:ARBA00027930 REMOVE specific (1-20) 1 TOO_GENERAL true but uninformative manual TOO_GENERAL Generic 'protein binding' terms are uninformative per GO curation guidelines. While BTB domains do mediate protein interactions, the specific interactors for KCTD18 are not experimentally established. Structural interpretation has suggested possible CUL3 binding, but the Balasco 2024 classification is disputed locally and would require direct experimental validation before annotation. The term should be replaced with a more specific function term once experimental evidence is available. human/KCTD4 GO:0042802 identical protein binding ARBA:ARBA00027930 ACCEPT specific (1-20) 1 human/KCTD7 GO:0042802 identical protein binding ARBA:ARBA00027930 ACCEPT specific (1-20) 1 human/KCTD8 GO:0042802 identical protein binding ARBA:ARBA00027930 ACCEPT specific (1-20) 1 human/KIF1A GO:0003774 cytoskeletal motor activity ARBA:ARBA00028547 ACCEPT specific (1-20) 10 human/KIF1A GO:0010970 transport along microtubule ARBA:ARBA00044586 ACCEPT general (21-200) 55 human/KIF24 GO:0007019 microtubule depolymerization ARBA:ARBA00092022 ACCEPT specific (1-20) 6 human/KIF2A GO:0000070 mitotic sister chromatid segregation ARBA:ARBA00033588 KEEP_AS_NON_CORE general (21-200) 22 human/KIF2A GO:0003774 cytoskeletal motor activity ARBA:ARBA00028547 KEEP_AS_NON_CORE specific (1-20) 10 human/KIF2A GO:0007019 microtubule depolymerization ARBA:ARBA00092022 ACCEPT specific (1-20) 6 human/KIF3A GO:0005829 cytosol ARBA:ARBA00029243 ACCEPT general (21-200) 73 human/KIF3A GO:0008092 cytoskeletal protein binding ARBA:ARBA00029239 MODIFY general (21-200) 53 NEEDS_MORE_SPECIFIC true but uninformative replacement term Microtubule binding (GO:0008017) is the accurate specific term. human/KIF3A GO:0008104 intracellular protein localization ARBA:ARBA00028253 KEEP_AS_NON_CORE very general (>200 descendants) 356 human/KIF3A GO:0010970 transport along microtubule ARBA:ARBA00044586 ACCEPT general (21-200) 55 human/KIF3A GO:0016939 kinesin II complex ARBA:ARBA00089375 ACCEPT leaf (0) 0 human/KIF3A GO:0044877 protein-containing complex binding ARBA:ARBA00026521 MARK_AS_OVER_ANNOTATED general (21-200) 108 TOO_GENERAL true but uninformative Uninformative Uninformative general binding term; kinesin II complex membership and microtubule binding capture the relevant interactions. human/KIF3B GO:0005737 cytoplasm ARBA:ARBA00026971 ACCEPT very general (>200 descendants) 1146 human/KIF3B GO:0008088 axo-dendritic transport ARBA:ARBA00093058 KEEP_AS_NON_CORE general (21-200) 27 human/KIFAP3 GO:0010970 transport along microtubule ARBA:ARBA00044586 ACCEPT general (21-200) 55 human/KIT GO:0002720 positive regulation of cytokine production involved in immune response ARBA:ARBA00090392 KEEP_AS_NON_CORE specific (1-20) 11 human/KIT GO:0006935 chemotaxis ARBA:ARBA00027707 KEEP_AS_NON_CORE general (21-200) 75 human/KIT GO:0008406 gonad development ARBA:ARBA00028782 KEEP_AS_NON_CORE general (21-200) 32 human/KIT GO:0016477 cell migration ARBA:ARBA00028795 KEEP_AS_NON_CORE very general (>200 descendants) 257 human/KIT GO:0030097 hemopoiesis ARBA:ARBA00028409 KEEP_AS_NON_CORE general (21-200) 161 human/KIT GO:0042127 regulation of cell population proliferation ARBA:ARBA00027546 ACCEPT very general (>200 descendants) 258 human/KIT GO:0043410 positive regulation of MAPK cascade ARBA:ARBA00027228 ACCEPT specific (1-20) 10 human/KIT GO:0045321 leukocyte activation ARBA:ARBA00091994 KEEP_AS_NON_CORE general (21-200) 181 human/KIT GO:0050793 regulation of developmental process ARBA:ARBA00028689 KEEP_AS_NON_CORE very general (>200 descendants) 1542 human/KITLG GO:0003006 developmental process involved in reproduction ARBA:ARBA00026397 KEEP_AS_NON_CORE very general (>200 descendants) 482 human/KITLG GO:0048513 animal organ development ARBA:ARBA00029247 KEEP_AS_NON_CORE very general (>200 descendants) 1888 human/KLB GO:0017134 fibroblast growth factor binding ARBA:ARBA00085876 ACCEPT leaf (0) 0 human/KRAS GO:0000165 MAPK cascade ARBA:ARBA00029221 ACCEPT specific (1-20) 18 human/KRIT1 GO:0030695 GTPase regulator activity ARBA:ARBA00026642 MODIFY specific (1-20) 7 OTHER_TERM different term needed replacement term The early two-hybrid paper suggested KRIT1 might regulate Krev-1, but later direct binding and mutagenesis establish a GTP-dependent Rap1 effector. These experiments do not show nucleotide exchange or GTPase activation. Use small GTPase binding to express the demonstrated molecular interaction. human/KRT19 GO:0005829 cytosol ARBA:ARBA00029243 ACCEPT general (21-200) 73 human/LAMP1 GO:0007042 lysosomal lumen acidification ARBA:ARBA00092063 ACCEPT leaf (0) 0 human/LAMP1 GO:0008200 ion channel inhibitor activity ARBA:ARBA00027322 ACCEPT specific (1-20) 7 human/LAMP1 GO:0035577 azurophil granule membrane ARBA:ARBA00090621 KEEP_AS_NON_CORE leaf (0) 0 human/LAMP1 GO:0101003 ficolin-1-rich granule membrane ARBA:ARBA00085572 KEEP_AS_NON_CORE leaf (0) 0 human/LATS1 GO:0000922 spindle pole ARBA:ARBA00092938 ACCEPT specific (1-20) 5 human/LATS1 GO:0035329 hippo signaling ARBA:ARBA00091361 ACCEPT leaf (0) 0 human/LATS1 GO:0044772 mitotic cell cycle phase transition ARBA:ARBA00027525 KEEP_AS_NON_CORE specific (1-20) 4 human/LATS1 GO:0090090 negative regulation of canonical Wnt signaling pathway ARBA:ARBA00027950 KEEP_AS_NON_CORE leaf (0) 0 human/LBR GO:0016627 oxidoreductase activity, acting on the CH-CH group of donors ARBA:ARBA00028473 MODIFY general (21-200) 168 NEEDS_MORE_SPECIFIC true but uninformative replacement term Correct but too general; the specific, experimentally established activity is NADPH-dependent Delta14-sterol reductase activity. human/LCK GO:0002429 immune response-activating cell surface receptor signaling pathway ARBA:ARBA00089168 ACCEPT general (21-200) 36 human/LCK GO:0035556 intracellular signal transduction ARBA:ARBA00026887 KEEP_AS_NON_CORE general (21-200) 195 human/LCK GO:0051240 positive regulation of multicellular organismal process ARBA:ARBA00028891 MARK_AS_OVER_ANNOTATED very general (>200 descendants) 565 TOO_GENERAL true but uninformative general Extremely general term that conveys no information about LCK function. human/LCP2 GO:0002376 immune system process ARBA:ARBA00027799 MODIFY very general (>200 descendants) 673 NEEDS_MORE_SPECIFIC true but uninformative replacement term Correct but too general. LCP2 is an adaptor in antigen-receptor signaling; the specific, well-supported process is T cell receptor signaling pathway (plus FcERI signaling in mast cells). human/LGALS3 GO:0042129 regulation of T cell proliferation ARBA:ARBA00085953 KEEP_AS_NON_CORE general (21-200) 29 human/LGALS3 GO:0046636 negative regulation of alpha-beta T cell activation ARBA:ARBA00091948 KEEP_AS_NON_CORE specific (1-20) 18 human/LGALS3 GO:0048018 receptor ligand activity ARBA:ARBA00028558 MARK_AS_OVER_ANNOTATED general (21-200) 34 TOO_GENERAL true but uninformative generic Less precise than the experimentally supported receptor ligand inhibitor activity; generic prediction. human/LGALS3 GO:0070232 regulation of T cell apoptotic process ARBA:ARBA00097057 KEEP_AS_NON_CORE specific (1-20) 17 human/LGALS3 GO:0071677 positive regulation of mononuclear cell migration ARBA:ARBA00092096 KEEP_AS_NON_CORE specific (1-20) 19 human/LIMD1 GO:0001666 response to hypoxia ARBA:ARBA00027678 ACCEPT specific (1-20) 8 human/LIMD1 GO:0035278 miRNA-mediated gene silencing by inhibition of translation ARBA:ARBA00091152 ACCEPT leaf (0) 0 human/LIMD1 GO:0035331 negative regulation of hippo signaling ARBA:ARBA00091342 ACCEPT leaf (0) 0 human/LIPE GO:0004771 sterol ester esterase activity ARBA:ARBA00087653 KEEP_AS_NON_CORE leaf (0) 0 human/LIPE GO:0050253 retinyl-palmitate esterase activity ARBA:ARBA00088680 KEEP_AS_NON_CORE specific (1-20) 2 human/LMAN1 GO:0012505 endomembrane system ARBA:ARBA00028953 MARK_AS_OVER_ANNOTATED very general (>200 descendants) 357 TOO_GENERAL true but uninformative general Overly general parent term; the specific ERGIC membrane, ER membrane and Golgi membrane annotations capture the localization precisely. human/LMAN1L GO:0005793 endoplasmic reticulum-Golgi intermediate compartment ARBA:ARBA00028710 KEEP_AS_NON_CORE specific (1-20) 2 human/LMAN1L GO:0012505 endomembrane system ARBA:ARBA00028953 MARK_AS_OVER_ANNOTATED very general (>200 descendants) 357 TOO_GENERAL true but uninformative Generic Generic high-level compartment term superseded by the more specific ERGIC/ER membrane annotations; not informative on its own. human/LMX1B GO:0043565 sequence-specific DNA binding ARBA:ARBA00026779 MODIFY general (21-200) 60 NEEDS_MORE_SPECIFIC true but uninformative replacement term The ARBA prediction captures specificity but not DNA strandedness. Direct LMX1B binding-site assays and the existing IDA annotation support sequence-specific double-stranded DNA binding. human/LNPEP GO:0002474 antigen processing and presentation of peptide antigen via MHC class I ARBA:ARBA00088849 ACCEPT specific (1-20) 9 human/LNPEP GO:0031410 cytoplasmic vesicle ARBA:ARBA00027190 MODIFY very general (>200 descendants) 274 NEEDS_MORE_SPECIFIC true but uninformative replacement term The broad vesicle location is directionally correct, but type-II topology and direct endosomal/GLUT4-vesicle evidence support the membrane-specific child term. human/LNX1 GO:0030054 cell junction ARBA:ARBA00028333 ACCEPT general (21-200) 189 human/LOX GO:0071953 elastic fiber ARBA:ARBA00084594 ACCEPT specific (1-20) 3 human/LOXHD1 GO:0007605 sensory perception of sound ARBA:ARBA00033578 ACCEPT specific (1-20) 2 human/LOXL1 GO:0071953 elastic fiber ARBA:ARBA00084594 ACCEPT specific (1-20) 3 human/LOXL2 GO:0071953 elastic fiber ARBA:ARBA00084594 ACCEPT specific (1-20) 3 human/LOXL3 GO:0009888 tissue development ARBA:ARBA00028065 KEEP_AS_NON_CORE very general (>200 descendants) 1023 human/LOXL3 GO:0048513 animal organ development ARBA:ARBA00029247 KEEP_AS_NON_CORE very general (>200 descendants) 1888 human/LOXL3 GO:0071953 elastic fiber ARBA:ARBA00084594 MARK_AS_OVER_ANNOTATED specific (1-20) 3 UNCLASSIFIED unclassified Elastin oxidation supports a relationship with elastic fibers, but substrate use does not establish stable localization within the fiber (PMID:17018530). human/LOXL4 GO:0071953 elastic fiber ARBA:ARBA00084594 KEEP_AS_NON_CORE specific (1-20) 3 human/LPA GO:0034185 apolipoprotein binding ARBA:ARBA00090479 ACCEPT specific (1-20) 1 human/LPAR1 GO:0007204 positive regulation of cytosolic calcium ion concentration ARBA:ARBA00028136 ACCEPT specific (1-20) 8 human/LPAR1 GO:0008289 lipid binding ARBA:ARBA00027537 MODIFY general (21-200) 94 NEEDS_MORE_SPECIFIC true but uninformative replacement term Lipid binding is directionally correct but too broad. LPAR1 directly binds lysophosphatidic acid and transduces its signal, and GO:0035727 states that demonstrated ligand interaction without suggesting generic binding to unrelated lipids or phospholipids. human/LPAR2 GO:0007204 positive regulation of cytosolic calcium ion concentration ARBA:ARBA00028136 ACCEPT specific (1-20) 8 human/LPAR2 GO:0008289 lipid binding ARBA:ARBA00027537 MODIFY general (21-200) 94 NEEDS_MORE_SPECIFIC true but uninformative replacement term Lysophosphatidic acid binding is the experimentally established ligand-recognition activity and is more informative than the true parent binding term. The broad parent does not itself imply binding to unrelated lipids. human/LPAR3 GO:0007204 positive regulation of cytosolic calcium ion concentration ARBA:ARBA00028136 ACCEPT specific (1-20) 8 human/LPAR3 GO:0008289 lipid binding ARBA:ARBA00027537 MODIFY general (21-200) 94 NEEDS_MORE_SPECIFIC true but uninformative replacement term Lysophosphatidic acid binding is the experimentally established ligand-recognition activity and is more informative than the true parent binding term. The broad parent does not itself imply binding to unrelated lipids. human/LPCAT1 GO:0042171 lysophosphatidic acid acyltransferase activity ARBA:ARBA00027459 ACCEPT specific (1-20) 2 human/LPCAT2 GO:0006650 glycerophospholipid metabolic process ARBA:ARBA00028631 KEEP_AS_NON_CORE general (21-200) 58 human/LPCAT2 GO:0031984 organelle subcompartment ARBA:ARBA00026532 MARK_AS_OVER_ANNOTATED general (21-200) 92 TOO_GENERAL true but uninformative generic Too generic. LPCAT2 has specific localizations (ER membrane, lipid droplet) that are much more informative. human/LPCAT2 GO:0042171 lysophosphatidic acid acyltransferase activity ARBA:ARBA00027459 ACCEPT specific (1-20) 2 human/LPCAT4 GO:0042171 lysophosphatidic acid acyltransferase activity ARBA:ARBA00027459 REMOVE specific (1-20) 2 WRONG_ACTIVITY wrong manual WRONG_ACTIVITY PMID:18458083 explicitly reports no appreciable lysophosphatidic-acid or glycerol-3-phosphate acylation by human LPCAT4. The ARBA assignment appears to over-transfer a family-associated activity. human/LPL GO:0006641 triglyceride metabolic process ARBA:ARBA00028707 ACCEPT specific (1-20) 4 human/LPL GO:0016042 lipid catabolic process ARBA:ARBA00028909 ACCEPT general (21-200) 154 human/LRATD2 GO:0005737 cytoplasm ARBA:ARBA00026971 ACCEPT very general (>200 descendants) 1146 human/LRP1 GO:0001523 retinoid metabolic process ARBA:ARBA00028293 KEEP_AS_NON_CORE specific (1-20) 18 human/LRP1 GO:0005041 low-density lipoprotein particle receptor activity ARBA:ARBA00043573 ACCEPT leaf (0) 0 human/LRP1 GO:0005769 early endosome ARBA:ARBA00028567 ACCEPT specific (1-20) 7 human/LRP1 GO:0006898 receptor-mediated endocytosis ARBA:ARBA00044584 ACCEPT general (21-200) 30 human/LRP1 GO:0030100 regulation of endocytosis ARBA:ARBA00085851 KEEP_AS_NON_CORE general (21-200) 48 human/LRP1 GO:0032050 clathrin heavy chain binding ARBA:ARBA00092116 ACCEPT leaf (0) 0 human/LRP1 GO:0044877 protein-containing complex binding ARBA:ARBA00026521 MARK_AS_OVER_ANNOTATED general (21-200) 108 TOO_GENERAL true but uninformative More informative For GO:0044877 (protein-containing complex binding), the IEA annotation with qualifier enables from GO_REF:0000117 may reflect a real assay result or interaction, but this GO term does not identify the specific receptor, ligand-binding, cargo-clearance, endocytic, or localization annotation that explains LRP1's role in LDLR-family ligand binding and receptor-mediated internalization/clearance of lipoprotein, apolipoprotein, protease-inhibitor, amyloid-beta, tau, and other cargo complexes. More informative gene-specific annotations are present, so this is marked over-annotated rather than accepted as a core function. human/LRP1 GO:0051050 positive regulation of transport ARBA:ARBA00034593 ACCEPT very general (>200 descendants) 314 human/LRP1 GO:0051246 regulation of protein metabolic process ARBA:ARBA00028884 KEEP_AS_NON_CORE very general (>200 descendants) 442 human/LRP10 GO:0016192 vesicle-mediated transport ARBA:ARBA00028249 ACCEPT very general (>200 descendants) 232 human/LRP12 GO:0001764 neuron migration ARBA:ARBA00089626 KEEP_AS_NON_CORE specific (1-20) 11 human/LRP12 GO:0031175 neuron projection development ARBA:ARBA00026765 KEEP_AS_NON_CORE general (21-200) 124 human/LRP1B GO:0006898 receptor-mediated endocytosis ARBA:ARBA00044584 ACCEPT general (21-200) 30 human/LRP2 GO:0001523 retinoid metabolic process ARBA:ARBA00028293 KEEP_AS_NON_CORE specific (1-20) 18 human/LRP2 GO:0005041 low-density lipoprotein particle receptor activity ARBA:ARBA00043573 MODIFY leaf (0) 0 TOO_SPECIFIC overreach replacement term The current GO:0005041 requires low-density-lipoprotein-particle binding and uptake; family membership and this electronic rule do not establish that substrate-specific activity. The conserved multiligand uptake role supports the more defensible cargo receptor activity term. human/LRP2 GO:0007165 signal transduction ARBA:ARBA00029050 MARK_AS_OVER_ANNOTATED very general (>200 descendants) 937 TOO_GENERAL true but uninformative Generic Generic signal transduction is too broad: LRP2 is an endocytic cargo receptor, and this electronic rule does not establish an autonomous signaling output. human/LRP2 GO:0030001 metal ion transport ARBA:ARBA00028072 KEEP_AS_NON_CORE very general (>200 descendants) 347 human/LRP2 GO:0043235 signaling receptor complex ARBA:ARBA00029086 UNDECIDED general (21-200) 113 human/LRP2 GO:0051087 protein-folding chaperone binding ARBA:ARBA00088077 KEEP_AS_NON_CORE specific (1-20) 1 human/LRP2 GO:0051180 vitamin transport ARBA:ARBA00026766 KEEP_AS_NON_CORE general (21-200) 52 human/LRP3 GO:0016192 vesicle-mediated transport ARBA:ARBA00028249 KEEP_AS_NON_CORE very general (>200 descendants) 232 human/LRP4 GO:0048731 system development ARBA:ARBA00027702 KEEP_AS_NON_CORE very general (>200 descendants) 2438 human/LRP4 GO:0160108 animal gross anatomical part developmental process ARBA:ARBA00098139 KEEP_AS_NON_CORE very general (>200 descendants) 3010 human/LRP5 GO:0008284 positive regulation of cell population proliferation ARBA:ARBA00027538 KEEP_AS_NON_CORE general (21-200) 85 human/LRP5 GO:0009887 animal organ morphogenesis ARBA:ARBA00028067 KEEP_AS_NON_CORE very general (>200 descendants) 585 human/LRP5 GO:0009888 tissue development ARBA:ARBA00028065 KEEP_AS_NON_CORE very general (>200 descendants) 1023 human/LRP5 GO:0015026 coreceptor activity ARBA:ARBA00026504 ACCEPT leaf (0) 0 human/LRP5 GO:0045597 positive regulation of cell differentiation ARBA:ARBA00028476 KEEP_AS_NON_CORE very general (>200 descendants) 224 human/LRP5 GO:0045667 regulation of osteoblast differentiation ARBA:ARBA00084601 KEEP_AS_NON_CORE specific (1-20) 2 human/LRP5 GO:0045787 positive regulation of cell cycle ARBA:ARBA00026693 KEEP_AS_NON_CORE general (21-200) 118 human/LRP5 GO:1990851 Wnt-Frizzled-LRP5/6 complex ARBA:ARBA00089182 ACCEPT leaf (0) 0 human/LRP6 GO:0005769 early endosome ARBA:ARBA00028567 KEEP_AS_NON_CORE specific (1-20) 7 human/LRP6 GO:0009888 tissue development ARBA:ARBA00028065 KEEP_AS_NON_CORE very general (>200 descendants) 1023 human/LRP6 GO:0015026 coreceptor activity ARBA:ARBA00026504 ACCEPT leaf (0) 0 human/LRP6 GO:0016192 vesicle-mediated transport ARBA:ARBA00028249 KEEP_AS_NON_CORE very general (>200 descendants) 232 human/LRP6 GO:0030901 midbrain development ARBA:ARBA00088343 KEEP_AS_NON_CORE specific (1-20) 8 human/LRP6 GO:0042981 regulation of apoptotic process ARBA:ARBA00027086 KEEP_AS_NON_CORE very general (>200 descendants) 218 human/LRP6 GO:0043009 chordate embryonic development ARBA:ARBA00027425 KEEP_AS_NON_CORE general (21-200) 101 human/LRP6 GO:0045787 positive regulation of cell cycle ARBA:ARBA00026693 KEEP_AS_NON_CORE general (21-200) 118 human/LRP6 GO:0045944 positive regulation of transcription by RNA polymerase II ARBA:ARBA00027996 KEEP_AS_NON_CORE specific (1-20) 12 human/LRP6 GO:0048646 anatomical structure formation involved in morphogenesis ARBA:ARBA00028539 KEEP_AS_NON_CORE very general (>200 descendants) 488 human/LRP6 GO:0071542 dopaminergic neuron differentiation ARBA:ARBA00092424 KEEP_AS_NON_CORE specific (1-20) 1 human/LRP6 GO:1990851 Wnt-Frizzled-LRP5/6 complex ARBA:ARBA00089182 ACCEPT leaf (0) 0 human/LRP8 GO:0004888 transmembrane signaling receptor activity ARBA:ARBA00026973 MODIFY very general (>200 descendants) 327 NEEDS_MORE_SPECIFIC true but uninformative replacement term The ARBA receptor term is unnecessarily generic; current GO:0038025 captures the established Reelin receptor activity without importing unrelated LDLR-family signaling. human/LRP8 GO:0005041 low-density lipoprotein particle receptor activity ARBA:ARBA00043573 KEEP_AS_NON_CORE leaf (0) 0 human/LRP8 GO:0006897 endocytosis ARBA:ARBA00027119 ACCEPT general (21-200) 64 human/LRP8 GO:0007165 signal transduction ARBA:ARBA00029050 MODIFY very general (>200 descendants) 937 NEEDS_MORE_SPECIFIC true but uninformative replacement term Generic signal transduction should be replaced by the directly established Reelin-mediated signaling pathway. human/LRP8 GO:0030229 very-low-density lipoprotein particle receptor activity ARBA:ARBA00085597 ACCEPT leaf (0) 0 human/LRP8 GO:0034185 apolipoprotein binding ARBA:ARBA00090479 ACCEPT specific (1-20) 1 human/LRRK2 GO:0005829 cytosol ARBA:ARBA00029243 ACCEPT general (21-200) 73 human/LRRK2 GO:0007030 Golgi organization ARBA:ARBA00091973 ACCEPT specific (1-20) 15 human/LRRK2 GO:0007166 cell surface receptor signaling pathway ARBA:ARBA00029053 KEEP_AS_NON_CORE very general (>200 descendants) 403 human/LRRK2 GO:0009653 anatomical structure morphogenesis ARBA:ARBA00026583 MARK_AS_OVER_ANNOTATED very general (>200 descendants) 1501 TOO_GENERAL true but uninformative broad Anatomical structure morphogenesis is very broad. human/LRRK2 GO:0009968 negative regulation of signal transduction ARBA:ARBA00027208 KEEP_AS_NON_CORE very general (>200 descendants) 244 human/LRRK2 GO:0010468 regulation of gene expression ARBA:ARBA00028334 KEEP_AS_NON_CORE very general (>200 descendants) 874 human/LRRK2 GO:0016192 vesicle-mediated transport ARBA:ARBA00028249 ACCEPT very general (>200 descendants) 232 human/LRRK2 GO:0030159 signaling receptor complex adaptor activity ARBA:ARBA00085896 UNDECIDED specific (1-20) 2 human/LRRK2 GO:0030162 regulation of proteolysis ARBA:ARBA00027404 KEEP_AS_NON_CORE general (21-200) 38 human/LRRK2 GO:0030182 neuron differentiation ARBA:ARBA00027575 MARK_AS_OVER_ANNOTATED very general (>200 descendants) 323 UNCLASSIFIED unclassified Neuron differentiation is developmental. human/LRRK2 GO:0035640 exploration behavior ARBA:ARBA00093010 MARK_AS_OVER_ANNOTATED specific (1-20) 1 INDIRECT_EFFECT overreach phenotype Exploration behavior is a high-level organismal phenotype. human/LRRK2 GO:0042391 regulation of membrane potential ARBA:ARBA00028934 KEEP_AS_NON_CORE general (21-200) 154 human/LRRK2 GO:0043195 terminal bouton ARBA:ARBA00084429 KEEP_AS_NON_CORE specific (1-20) 17 human/LRRK2 GO:0048513 animal organ development ARBA:ARBA00029247 MARK_AS_OVER_ANNOTATED very general (>200 descendants) 1888 TOO_GENERAL true but uninformative broad Animal organ development is very broad. human/LRRK2 GO:0050804 modulation of chemical synaptic transmission ARBA:ARBA00029187 KEEP_AS_NON_CORE general (21-200) 116 human/LRRK2 GO:0051239 regulation of multicellular organismal process ARBA:ARBA00028859 KEEP_AS_NON_CORE very general (>200 descendants) 1807 human/LRRK2 GO:0051247 positive regulation of protein metabolic process ARBA:ARBA00028881 KEEP_AS_NON_CORE general (21-200) 138 human/LRRK2 GO:0060627 regulation of vesicle-mediated transport ARBA:ARBA00029251 ACCEPT general (21-200) 119 human/LRRK2 GO:0070013 intracellular organelle lumen ARBA:ARBA00027917 KEEP_AS_NON_CORE very general (>200 descendants) 239 human/LRRK2 GO:1902531 regulation of intracellular signal transduction ARBA:ARBA00027126 KEEP_AS_NON_CORE very general (>200 descendants) 278 human/LRRK2 GO:1904887 Wnt signalosome assembly ARBA:ARBA00089044 KEEP_AS_NON_CORE leaf (0) 0 human/LSS GO:0006695 cholesterol biosynthetic process ARBA:ARBA00087369 ACCEPT leaf (0) 0 human/LY96 GO:0002221 pattern recognition receptor signaling pathway ARBA:ARBA00033911 ACCEPT general (21-200) 47 human/LYN GO:0002758 innate immune response-activating signaling pathway ARBA:ARBA00034398 KEEP_AS_NON_CORE general (21-200) 51 human/LYN GO:0002862 negative regulation of inflammatory response to antigenic stimulus ARBA:ARBA00090107 KEEP_AS_NON_CORE specific (1-20) 10 human/LYN GO:0005829 cytosol ARBA:ARBA00029243 KEEP_AS_NON_CORE general (21-200) 73 human/LYN GO:0006952 defense response ARBA:ARBA00026315 KEEP_AS_NON_CORE general (21-200) 175 human/LYN GO:0008284 positive regulation of cell population proliferation ARBA:ARBA00027538 KEEP_AS_NON_CORE general (21-200) 85 human/LYN GO:0035556 intracellular signal transduction ARBA:ARBA00026887 KEEP_AS_NON_CORE general (21-200) 195 human/LYN GO:0038096 Fc-gamma receptor signaling pathway involved in phagocytosis ARBA:ARBA00088071 KEEP_AS_NON_CORE leaf (0) 0 human/LYN GO:0045121 membrane raft ARBA:ARBA00028509 ACCEPT specific (1-20) 6 human/LYN GO:0050900 leukocyte migration ARBA:ARBA00091273 KEEP_AS_NON_CORE general (21-200) 63 human/LYN GO:0071345 cellular response to cytokine stimulus ARBA:ARBA00027915 KEEP_AS_NON_CORE general (21-200) 149 human/LYN GO:0071396 cellular response to lipid ARBA:ARBA00027803 KEEP_AS_NON_CORE general (21-200) 91 human/LYN GO:0120035 regulation of plasma membrane bounded cell projection organization ARBA:ARBA00028050 KEEP_AS_NON_CORE general (21-200) 122 human/MAD2L1 GO:0051783 regulation of nuclear division ARBA:ARBA00027796 ACCEPT general (21-200) 31 human/MAD2L1 GO:1901991 negative regulation of mitotic cell cycle phase transition ARBA:ARBA00044401 ACCEPT specific (1-20) 15 human/MAD2L1 GO:1990728 mitotic spindle assembly checkpoint MAD1-MAD2 complex ARBA:ARBA00088969 ACCEPT leaf (0) 0 human/MAD2L2 GO:0010717 regulation of epithelial to mesenchymal transition ARBA:ARBA00085208 KEEP_AS_NON_CORE specific (1-20) 19 human/MAGI1 GO:0005737 cytoplasm ARBA:ARBA00026971 KEEP_AS_NON_CORE very general (>200 descendants) 1146 human/MAGI1 GO:0005911 cell-cell junction ARBA:ARBA00028427 ACCEPT general (21-200) 38 human/MAGI1 GO:0016020 membrane ARBA:ARBA00028763 MODIFY very general (>200 descendants) 895 NEEDS_MORE_SPECIFIC true but uninformative replacement term Replace the overly broad membrane term with plasma membrane and bicellular tight junction, both already supported by direct and curated evidence. human/MAGT1 GO:0006487 protein N-linked glycosylation ARBA:ARBA00085866 ACCEPT specific (1-20) 11 human/MAGT1 GO:0008250 oligosaccharyltransferase complex ARBA:ARBA00092378 ACCEPT specific (1-20) 2 human/MAGT1 GO:0015095 magnesium ion transmembrane transporter activity ARBA:ARBA00026593 MARK_AS_OVER_ANNOTATED specific (1-20) 2 INDIRECT_EFFECT overreach indirect "Over-annotation. This ARBA electronic annotation assigns a direct Mg2+ transporter activity based on the historical name/family, but the best-supported molecular function of MAGT1 is the thioredoxin-like OST-B oxidoreductase activity. UniProt downgrades the Mg2+ role to indirect/probable and no longer uses ""magnesium transporter"" as the primary name. There is no robust evidence that MAGT1 itself is a Mg2+ channel/transporter; mark as over-annotated." human/MAN1B1 GO:0009100 glycoprotein metabolic process ARBA:ARBA00027558 MARK_AS_OVER_ANNOTATED general (21-200) 66 TOO_GENERAL true but uninformative general Over-general parent process; the specific glycan-trimming/ERAD terms are preferred. human/MAN1B1 GO:0036503 ERAD pathway ARBA:ARBA00029018 ACCEPT specific (1-20) 3 human/MAP1LC3B GO:0000045 autophagosome assembly ARBA:ARBA00088808 ACCEPT specific (1-20) 8 human/MAP1LC3B GO:0000422 autophagy of mitochondrion ARBA:ARBA00026840 ACCEPT specific (1-20) 5 human/MAP1LC3B GO:0005543 phospholipid binding ARBA:ARBA00027145 ACCEPT specific (1-20) 19 human/MAP1LC3B GO:0005776 autophagosome ARBA:ARBA00033591 ACCEPT specific (1-20) 4 human/MAP1LC3B GO:0016020 membrane ARBA:ARBA00028763 ACCEPT very general (>200 descendants) 895 human/MAP1LC3B GO:0031625 ubiquitin protein ligase binding ARBA:ARBA00028807 KEEP_AS_NON_CORE leaf (0) 0 human/MAP1LC3B GO:0097352 autophagosome maturation ARBA:ARBA00033540 ACCEPT specific (1-20) 1 human/MAP2K1 GO:0005078 MAP kinase scaffold activity ARBA:ARBA00086240 ACCEPT leaf (0) 0 human/MAP2K1 GO:0005739 mitochondrion ARBA:ARBA00026962 UNDECIDED general (21-200) 70 human/MAP2K1 GO:0005769 early endosome ARBA:ARBA00028567 KEEP_AS_NON_CORE specific (1-20) 7 human/MAP2K1 GO:0005770 late endosome ARBA:ARBA00028569 KEEP_AS_NON_CORE specific (1-20) 13 human/MAP2K1 GO:0005925 focal adhesion ARBA:ARBA00028361 UNDECIDED leaf (0) 0 human/MAP2K1 GO:0032872 regulation of stress-activated MAPK cascade ARBA:ARBA00026638 REMOVE specific (1-20) 5 WRONG_PARALOG wrong manual WRONG_PARALOG MEK1 functions specifically in the ERK1/2 cascade and does not phosphorylate JNK or p38; an ARBA-propagated SAPK-cascade regulation term contradicts its established specificity. human/MAP2K1 GO:0043539 protein serine/threonine kinase activator activity ARBA:ARBA00085523 MODIFY specific (1-20) 2 OTHER_TERM different term needed replacement term As for the IDA row, 'activator' annotations for MEK1 rest on its activation of ERK, which is catalytic; GO:0004708 is the correct MF. MEK1's genuinely non-catalytic promotion of KSR-BRAF dimerization is captured by the (non-core) MAP kinase scaffold activity rows. human/MAP2K1 GO:0090170 regulation of Golgi inheritance ARBA:ARBA00028400 KEEP_AS_NON_CORE leaf (0) 0 human/MAP2K1 GO:0097110 scaffold protein binding ARBA:ARBA00034605 ACCEPT leaf (0) 0 human/MAP2K1 GO:2000641 regulation of early endosome to late endosome transport ARBA:ARBA00028332 KEEP_AS_NON_CORE specific (1-20) 2 human/MAP2K2 GO:0005078 MAP kinase scaffold activity ARBA:ARBA00086240 UNDECIDED leaf (0) 0 human/MAP2K2 GO:0005739 mitochondrion ARBA:ARBA00026962 UNDECIDED general (21-200) 70 human/MAP2K2 GO:0005769 early endosome ARBA:ARBA00028567 UNDECIDED specific (1-20) 7 human/MAP2K2 GO:0005770 late endosome ARBA:ARBA00028569 UNDECIDED specific (1-20) 13 human/MAP2K2 GO:0005925 focal adhesion ARBA:ARBA00028361 UNDECIDED leaf (0) 0 human/MAP2K2 GO:0032872 regulation of stress-activated MAPK cascade ARBA:ARBA00026638 UNDECIDED specific (1-20) 5 human/MAP2K2 GO:0043539 protein serine/threonine kinase activator activity ARBA:ARBA00085523 ACCEPT specific (1-20) 2 human/MAP2K2 GO:0090170 regulation of Golgi inheritance ARBA:ARBA00028400 UNDECIDED leaf (0) 0 human/MAP2K2 GO:0097110 scaffold protein binding ARBA:ARBA00034605 ACCEPT leaf (0) 0 human/MAP2K2 GO:2000641 regulation of early endosome to late endosome transport ARBA:ARBA00028332 UNDECIDED specific (1-20) 2 human/MAP2K3 GO:0031098 stress-activated protein kinase signaling cascade ARBA:ARBA00035552 ACCEPT specific (1-20) 3 human/MAP2K3 GO:0038066 p38MAPK cascade ARBA:ARBA00088051 ACCEPT leaf (0) 0 human/MAP2K3 GO:0090398 cellular senescence ARBA:ARBA00086844 KEEP_AS_NON_CORE specific (1-20) 3 human/MAP2K3 GO:1902531 regulation of intracellular signal transduction ARBA:ARBA00027126 MARK_AS_OVER_ANNOTATED very general (>200 descendants) 278 TOO_GENERAL true but uninformative vague MKK3 is a core transducing kinase of the p38 cascade rather than a regulator of signal transduction; its role is captured precisely by p38MAPK cascade (GO:0038066) and MAP kinase kinase activity. This vague regulation term adds no information and over-states a regulatory role. human/MAP2K4 GO:0005829 cytosol ARBA:ARBA00029243 ACCEPT general (21-200) 73 human/MAP2K4 GO:0007166 cell surface receptor signaling pathway ARBA:ARBA00029053 MARK_AS_OVER_ANNOTATED very general (>200 descendants) 403 INDIRECT_EFFECT overreach downstream MKK4 acts in intracellular MAPK cascades downstream of many inputs (stresses, cytokine receptors, TCR), but it is not a component of any specific cell-surface receptor pathway; the broad receptor-signalling term adds little and over-states a receptor-proximal role. The specific process is the JNK / stress-activated MAPK cascade. human/MAP2K4 GO:0033554 cellular response to stress ARBA:ARBA00028184 MODIFY very general (>200 descendants) 285 NEEDS_MORE_SPECIFIC true but uninformative replacement term Correct in spirit: MKK4 is activated by UV, irradiation, heat shock, hyperosmolarity, peroxide and cytokines. The informative process for its participation is the stress-activated MAPK cascade (GO:0051403), which MKK4 executes by activating JNK and p38. human/MAP2K5 GO:0007165 signal transduction ARBA:ARBA00029050 MODIFY very general (>200 descendants) 937 NEEDS_MORE_SPECIFIC true but uninformative replacement term Correct but too general. MEK5 functions specifically in the MEKK2/3-MEK5-ERK5 MAP kinase cascade, so ERK5 cascade (GO:0070375) is the appropriate specific process, as done for signal transduction in the MAP2K3/MAP2K6 reviews. human/MAP2K6 GO:0019901 protein kinase binding ARBA:ARBA00028598 KEEP_AS_NON_CORE specific (1-20) 15 human/MAP2K6 GO:0031098 stress-activated protein kinase signaling cascade ARBA:ARBA00035552 ACCEPT specific (1-20) 3 human/MAP2K6 GO:0038066 p38MAPK cascade ARBA:ARBA00088051 ACCEPT leaf (0) 0 human/MAP2K6 GO:0090398 cellular senescence ARBA:ARBA00086844 KEEP_AS_NON_CORE specific (1-20) 3 human/MAP2K6 GO:1902531 regulation of intracellular signal transduction ARBA:ARBA00027126 MARK_AS_OVER_ANNOTATED very general (>200 descendants) 278 TOO_GENERAL true but uninformative vague MKK6 is a core transducing kinase of the p38 cascade rather than a regulator of signal transduction; its role is captured precisely by p38MAPK cascade (GO:0038066) and MAP kinase kinase activity. This vague regulation term adds no information (consistent with the MAP2K3 review). human/MAP2K7 GO:0000287 magnesium ion binding ARBA:ARBA00028486 KEEP_AS_NON_CORE leaf (0) 0 human/MAP2K7 GO:0019901 protein kinase binding ARBA:ARBA00028598 KEEP_AS_NON_CORE specific (1-20) 15 human/MAP2K7 GO:0031098 stress-activated protein kinase signaling cascade ARBA:ARBA00035552 ACCEPT specific (1-20) 3 human/MAP2K7 GO:0043410 positive regulation of MAPK cascade ARBA:ARBA00027228 MARK_AS_OVER_ANNOTATED specific (1-20) 10 TOO_GENERAL true but uninformative already captured MKK7 is a component of the JNK MAPK cascade (the MAP2K tier), not a regulator external to it; participation is already captured by JNK cascade (GO:0007254) and stress-activated MAPK cascade. The regulation term is a redundant over-annotation. human/MAP2K7 GO:0090398 cellular senescence ARBA:ARBA00086844 KEEP_AS_NON_CORE specific (1-20) 3 human/MAP3K1 GO:0005829 cytosol ARBA:ARBA00029243 ACCEPT general (21-200) 73 human/MAP3K1 GO:0007166 cell surface receptor signaling pathway ARBA:ARBA00029053 KEEP_AS_NON_CORE very general (>200 descendants) 403 human/MAP3K2 GO:0035556 intracellular signal transduction ARBA:ARBA00026887 MODIFY general (21-200) 195 NEEDS_MORE_SPECIFIC true but uninformative replacement term Correct but uninformative; MEKK2 is an intracellular signalling kinase whose best-defined process is the MEK5-ERK5 cascade, in which it phosphorylates MEK5. Replaced by ERK5 cascade (GO:0070375), consistent with the MODIFY of the IDA annotation to the same term. human/MAP3K3 GO:0035556 intracellular signal transduction ARBA:ARBA00026887 MODIFY general (21-200) 195 NEEDS_MORE_SPECIFIC true but uninformative replacement term Correct but uninformative. The best-defined process for MEKK3 is the MEK5-ERK5 cascade, in which MEKK3 performs the MEK5-phosphorylation step (participation, not just requirement): MEKK3 binds MEK5 via PB1 domains, active MEKK3 drives ERK5 through MEK5, and MEKK3 activity is required for growth-factor activation of endogenous ERK5. ERK5 cascade (GO:0070375) is already carried by MAP2K5 and MAPK7, and is proposed identically for MAP3K2. human/MAP3K7 GO:0005102 signaling receptor binding ARBA:ARBA00027239 MARK_AS_OVER_ANNOTATED very general (>200 descendants) 380 INDIRECT_EFFECT overreach indirect TAK1 is recruited to receptor complexes mostly indirectly (via TRAF6, TAB2/3 and ubiquitin chains); a generic signaling receptor binding MF is uninformative and not established as direct. human/MAP3K7 GO:0019901 protein kinase binding ARBA:ARBA00028598 KEEP_AS_NON_CORE specific (1-20) 15 human/MAPK1 GO:0005769 early endosome ARBA:ARBA00028567 MARK_AS_OVER_ANNOTATED specific (1-20) 7 UNCLASSIFIED unclassified Falcon synthesis supports cytoplasmic/cytosolic and stimulus-dependent nuclear localization as core; the early endosome location is a context-/pathway-specific or high-throughput-derived assignment that should not be promoted to a core ERK2 localization without direct MAPK1-specific evidence in that compartment. human/MAPK1 GO:0005770 late endosome ARBA:ARBA00028569 MARK_AS_OVER_ANNOTATED specific (1-20) 13 UNCLASSIFIED unclassified Falcon synthesis supports cytoplasmic/cytosolic and stimulus-dependent nuclear localization as core; the late endosome location is a context-/pathway-specific or high- throughput-derived assignment that should not be promoted to a core ERK2 localization without direct MAPK1-specific evidence in that compartment. human/MAPK1 GO:0005794 Golgi apparatus ARBA:ARBA00028708 MARK_AS_OVER_ANNOTATED general (21-200) 48 UNCLASSIFIED unclassified Falcon synthesis supports cytoplasmic/cytosolic and stimulus-dependent nuclear localization as core; the Golgi apparatus location is a context-/pathway-specific or high-throughput-derived assignment that should not be promoted to a core ERK2 localization without direct MAPK1-specific evidence in that compartment. human/MAPK1 GO:0007173 epidermal growth factor receptor signaling pathway ARBA:ARBA00034174 KEEP_AS_NON_CORE specific (1-20) 3 human/MAPK1 GO:0010759 positive regulation of macrophage chemotaxis ARBA:ARBA00085235 KEEP_AS_NON_CORE leaf (0) 0 human/MAPK1 GO:0032206 positive regulation of telomere maintenance ARBA:ARBA00047239 MARK_AS_OVER_ANNOTATED specific (1-20) 11 INDIRECT_EFFECT overreach indirect This is a high-throughput screen-derived, indirect pathway outcome rather than a direct MAPK1 function; it should not be elevated to a core ERK2 annotation without direct mechanistic evidence. human/MAPK1 GO:0032872 regulation of stress-activated MAPK cascade ARBA:ARBA00026638 MARK_AS_OVER_ANNOTATED specific (1-20) 5 UNCLASSIFIED unclassified GO:0032872 is a stress-activated MAPK cascade term associated with JNK/p38 signaling, whereas MAPK1/ERK2 is curated here as the canonical ERK/MAPK cascade kinase. The automated inference overstates the evidence. human/MAPK1 GO:0034198 cellular response to amino acid starvation ARBA:ARBA00090477 KEEP_AS_NON_CORE specific (1-20) 1 human/MAPK1 GO:0051403 stress-activated MAPK cascade ARBA:ARBA00035551 MARK_AS_OVER_ANNOTATED specific (1-20) 2 UNCLASSIFIED unclassified GO:0051403 refers to stress-activated MAPK cascade biology associated with JNK/p38 signaling, not the canonical ERK1/ERK2 cascade. The automated inference should not be retained as a valid non-core MAPK1 annotation. human/MAPK1 GO:0051493 regulation of cytoskeleton organization ARBA:ARBA00027391 KEEP_AS_NON_CORE general (21-200) 110 human/MAPK1 GO:0061514 interleukin-34-mediated signaling pathway ARBA:ARBA00093749 KEEP_AS_NON_CORE leaf (0) 0 human/MAPK1 GO:0070371 ERK1 and ERK2 cascade ARBA:ARBA00085205 ACCEPT leaf (0) 0 human/MAPK1 GO:0070849 response to epidermal growth factor ARBA:ARBA00086481 KEEP_AS_NON_CORE specific (1-20) 1 human/MAPK1 GO:0072584 caveolin-mediated endocytosis ARBA:ARBA00028693 KEEP_AS_NON_CORE specific (1-20) 1 human/MAPK1 GO:0090170 regulation of Golgi inheritance ARBA:ARBA00028400 KEEP_AS_NON_CORE leaf (0) 0 human/MAPK1 GO:0097542 ciliary tip ARBA:ARBA00044587 MARK_AS_OVER_ANNOTATED leaf (0) 0 UNCLASSIFIED unclassified Falcon synthesis supports cytoplasmic/cytosolic and stimulus-dependent nuclear localization as core; the ciliary tip location is a context-/pathway-specific or high- throughput-derived assignment that should not be promoted to a core ERK2 localization without direct MAPK1-specific evidence in that compartment. human/MAPK1 GO:0120041 positive regulation of macrophage proliferation ARBA:ARBA00090059 KEEP_AS_NON_CORE leaf (0) 0 human/MAPK1 GO:2000641 regulation of early endosome to late endosome transport ARBA:ARBA00028332 KEEP_AS_NON_CORE specific (1-20) 2 human/MAPK14 GO:0032735 positive regulation of interleukin-12 production ARBA:ARBA00085778 KEEP_AS_NON_CORE leaf (0) 0 human/MAPK14 GO:0051149 positive regulation of muscle cell differentiation ARBA:ARBA00087706 KEEP_AS_NON_CORE specific (1-20) 15 human/MAPK14 GO:0051403 stress-activated MAPK cascade ARBA:ARBA00035551 ACCEPT specific (1-20) 2 human/MAPK14 GO:0071493 cellular response to UV-B ARBA:ARBA00092260 KEEP_AS_NON_CORE leaf (0) 0 human/MAPK14 GO:0090398 cellular senescence ARBA:ARBA00086844 KEEP_AS_NON_CORE specific (1-20) 3 human/MAPK14 GO:0098586 cellular response to virus ARBA:ARBA00033919 MARK_AS_OVER_ANNOTATED leaf (0) 0 TOO_GENERAL true but uninformative generic p38 activation is a generic stress/innate response; a single inhibitor-based study of Gal-9 induction does not make 'cellular response to virus' an informative MAPK14 annotation. human/MAPK3 GO:0005739 mitochondrion ARBA:ARBA00026962 MARK_AS_OVER_ANNOTATED general (21-200) 70 UNCLASSIFIED unclassified Compartment-restricted ERK pool described in reviews/ARBA; ERK1 is not a resident of this compartment and the annotation over-extends a transient or stimulus-specific association. human/MAPK3 GO:0005769 early endosome ARBA:ARBA00028567 MARK_AS_OVER_ANNOTATED specific (1-20) 7 UNCLASSIFIED unclassified Compartment-restricted ERK pool described in reviews/ARBA; ERK1 is not a resident of this compartment and the annotation over-extends a transient or stimulus-specific association. human/MAPK3 GO:0005770 late endosome ARBA:ARBA00028569 MARK_AS_OVER_ANNOTATED specific (1-20) 13 UNCLASSIFIED unclassified Compartment-restricted ERK pool described in reviews/ARBA; ERK1 is not a resident of this compartment and the annotation over-extends a transient or stimulus-specific association. human/MAPK3 GO:0005794 Golgi apparatus ARBA:ARBA00028708 MARK_AS_OVER_ANNOTATED general (21-200) 48 UNCLASSIFIED unclassified Compartment-restricted ERK pool described in reviews/ARBA; ERK1 is not a resident of this compartment and the annotation over-extends a transient or stimulus-specific association. human/MAPK3 GO:0005856 cytoskeleton ARBA:ARBA00029228 MARK_AS_OVER_ANNOTATED very general (>200 descendants) 300 UNCLASSIFIED unclassified Compartment-restricted ERK pool described in reviews/ARBA; ERK1 is not a resident of this compartment and the annotation over-extends a transient or stimulus-specific association. human/MAPK3 GO:0007173 epidermal growth factor receptor signaling pathway ARBA:ARBA00034174 KEEP_AS_NON_CORE specific (1-20) 3 human/MAPK3 GO:0010759 positive regulation of macrophage chemotaxis ARBA:ARBA00085235 KEEP_AS_NON_CORE leaf (0) 0 human/MAPK3 GO:0019902 phosphatase binding ARBA:ARBA00087319 KEEP_AS_NON_CORE specific (1-20) 5 human/MAPK3 GO:0032206 positive regulation of telomere maintenance ARBA:ARBA00047239 MARK_AS_OVER_ANNOTATED specific (1-20) 11 INDIRECT_EFFECT overreach indirect Derived from an RNAi screen hit; indirect and weak, over-annotation (as in MAPK1). human/MAPK3 GO:0032872 regulation of stress-activated MAPK cascade ARBA:ARBA00026638 MARK_AS_OVER_ANNOTATED specific (1-20) 5 WRONG_PARALOG wrong not a component ERK1 is not a component or specific regulator of the JNK/p38 cascades; cross-talk only. Consistent with MAPK1. human/MAPK3 GO:0034198 cellular response to amino acid starvation ARBA:ARBA00090477 KEEP_AS_NON_CORE specific (1-20) 1 human/MAPK3 GO:0051403 stress-activated MAPK cascade ARBA:ARBA00035551 MARK_AS_OVER_ANNOTATED specific (1-20) 2 UNCLASSIFIED unclassified ERK1 is a classical mitogen-activated MAPK; stress-activated MAPK cascade refers to JNK/p38. human/MAPK3 GO:0051493 regulation of cytoskeleton organization ARBA:ARBA00027391 KEEP_AS_NON_CORE general (21-200) 110 human/MAPK3 GO:0061514 interleukin-34-mediated signaling pathway ARBA:ARBA00093749 KEEP_AS_NON_CORE leaf (0) 0 human/MAPK3 GO:0070371 ERK1 and ERK2 cascade ARBA:ARBA00085205 ACCEPT leaf (0) 0 human/MAPK3 GO:0070849 response to epidermal growth factor ARBA:ARBA00086481 KEEP_AS_NON_CORE specific (1-20) 1 human/MAPK3 GO:0072584 caveolin-mediated endocytosis ARBA:ARBA00028693 KEEP_AS_NON_CORE specific (1-20) 1 human/MAPK3 GO:0090170 regulation of Golgi inheritance ARBA:ARBA00028400 KEEP_AS_NON_CORE leaf (0) 0 human/MAPK3 GO:0120041 positive regulation of macrophage proliferation ARBA:ARBA00090059 KEEP_AS_NON_CORE leaf (0) 0 human/MAPK3 GO:2000641 regulation of early endosome to late endosome transport ARBA:ARBA00028332 KEEP_AS_NON_CORE specific (1-20) 2 human/MAPK7 GO:0033554 cellular response to stress ARBA:ARBA00028184 KEEP_AS_NON_CORE very general (>200 descendants) 285 human/MAPK7 GO:0043066 negative regulation of apoptotic process ARBA:ARBA00027746 KEEP_AS_NON_CORE general (21-200) 79 human/MAPK8 GO:0000165 MAPK cascade ARBA:ARBA00029221 ACCEPT specific (1-20) 18 human/MAPK8 GO:0038095 Fc-epsilon receptor signaling pathway ARBA:ARBA00088066 KEEP_AS_NON_CORE specific (1-20) 4 human/MAPK8 GO:0090398 cellular senescence ARBA:ARBA00086844 KEEP_AS_NON_CORE specific (1-20) 3 human/MAT1A GO:0051259 protein complex oligomerization ARBA:ARBA00043446 MODIFY specific (1-20) 9 NEEDS_MORE_SPECIFIC true but uninformative replacement term The essence is correct but the term is too general; the specific homo-oligomerization of identical subunits is better captured by GO:0051289 protein homotetramerization, which is directly supported by the crystal structure. human/MBL2 GO:0001867 complement activation, lectin pathway ARBA:ARBA00091687 ACCEPT leaf (0) 0 human/MCL1 GO:0012501 programmed cell death ARBA:ARBA00028943 MODIFY general (21-200) 147 NEEDS_MORE_SPECIFIC true but uninformative replacement term The ARBA row should be tightened to MCL1's anti-apoptotic mitochondrial role rather than retained as a top-level programmed-cell-death assertion. human/MCL1 GO:0051400 BH domain binding ARBA:ARBA00088889 MODIFY specific (1-20) 4 NEEDS_MORE_SPECIFIC true but uninformative replacement term A broad BH-domain-binding row is directionally close but less precise than the BH3-domain binding term used for BCL2-family pro-survival grooves. human/MCL1 GO:0097136 Bcl-2 family protein complex ARBA:ARBA00034603 ACCEPT specific (1-20) 12 human/MCL1 GO:1902531 regulation of intracellular signal transduction ARBA:ARBA00027126 REMOVE very general (>200 descendants) 278 INDIRECT overreach manual INDIRECT The ARBA row is a high-level inference that loses the direct MOMP survival mechanism. human/MCL1 GO:2001233 regulation of apoptotic signaling pathway ARBA:ARBA00027033 MODIFY general (21-200) 57 NEEDS_MORE_SPECIFIC true but uninformative replacement term The ARBA parent term can be tightened to negative regulation of MOMP in apoptotic signaling. human/MCTS1 GO:0002188 translation reinitiation ARBA:ARBA00087686 ACCEPT leaf (0) 0 human/MEF2C GO:0000981 DNA-binding transcription factor activity, RNA polymerase II-specific ARBA:ARBA00029016 ACCEPT specific (1-20) 8 human/MEF2C GO:0030154 cell differentiation ARBA:ARBA00027429 ACCEPT very general (>200 descendants) 1345 human/MEF2C GO:0048513 animal organ development ARBA:ARBA00029247 MARK_AS_OVER_ANNOTATED very general (>200 descendants) 1888 TOO_GENERAL true but uninformative general Too general to be informative; specific developmental terms are present. human/MEFV GO:0032731 positive regulation of interleukin-1 beta production ARBA:ARBA00033916 ACCEPT leaf (0) 0 human/MEFV GO:0050727 regulation of inflammatory response ARBA:ARBA00045047 KEEP_AS_NON_CORE general (21-200) 95 human/MEFV GO:0051707 response to other organism ARBA:ARBA00029118 KEEP_AS_NON_CORE general (21-200) 199 human/MEGF10 GO:0033002 muscle cell proliferation ARBA:ARBA00093115 KEEP_AS_NON_CORE specific (1-20) 6 human/MEGF10 GO:0048468 cell development ARBA:ARBA00028665 MARK_AS_OVER_ANNOTATED very general (>200 descendants) 672 TOO_GENERAL true but uninformative general Too general to be informative. The more specific muscle-development rows cover this aspect, and none of it is core. human/MFF GO:0005737 cytoplasm ARBA:ARBA00026971 KEEP_AS_NON_CORE very general (>200 descendants) 1146 human/MFN2 GO:0007005 mitochondrion organization ARBA:ARBA00026723 ACCEPT general (21-200) 37 human/MGP GO:0048731 system development ARBA:ARBA00027702 KEEP_AS_NON_CORE very general (>200 descendants) 2438 human/MKKS GO:0003006 developmental process involved in reproduction ARBA:ARBA00026397 MARK_AS_OVER_ANNOTATED very general (>200 descendants) 482 INDIRECT_EFFECT overreach Indirect Indirect downstream phenotype assigned by ARBA electronic prediction; not a direct functional attribute of MKKS. human/MKKS GO:0048513 animal organ development ARBA:ARBA00029247 MARK_AS_OVER_ANNOTATED very general (>200 descendants) 1888 INDIRECT_EFFECT overreach indirect High-level developmental term from automated prediction; indirect phenotype, not a direct functional attribute. human/MKKS GO:0048731 system development ARBA:ARBA00027702 MARK_AS_OVER_ANNOTATED very general (>200 descendants) 2438 TOO_GENERAL true but uninformative Root Root-level system development term from automated prediction; not informative. human/MKS1 GO:0005929 cilium ARBA:ARBA00028353 ACCEPT general (21-200) 115 human/MLEC GO:0005783 endoplasmic reticulum ARBA:ARBA00028672 ACCEPT general (21-200) 100 human/MMAB GO:0008817 corrinoid adenosyltransferase activity ARBA:ARBA00086340 ACCEPT leaf (0) 0 human/MMAB GO:0009235 cobalamin metabolic process ARBA:ARBA00090606 ACCEPT specific (1-20) 2 human/MMGT1 GO:0012505 endomembrane system ARBA:ARBA00028953 KEEP_AS_NON_CORE very general (>200 descendants) 357 human/MOCOS GO:0032324 molybdopterin cofactor biosynthetic process ARBA:ARBA00043347 KEEP_AS_NON_CORE specific (1-20) 5 human/MOCS1 GO:0032324 molybdopterin cofactor biosynthetic process ARBA:ARBA00043347 KEEP_AS_NON_CORE specific (1-20) 5 human/MOCS2 GO:0032324 molybdopterin cofactor biosynthetic process ARBA:ARBA00043347 KEEP_AS_NON_CORE specific (1-20) 5 human/MORC3 GO:0140002 histone H3K4me3 reader activity ARBA:ARBA00093692 ACCEPT leaf (0) 0 human/MTCH2 GO:0070585 protein localization to mitochondrion ARBA:ARBA00028355 KEEP_AS_NON_CORE specific (1-20) 7 human/MTHFD1 GO:0005829 cytosol ARBA:ARBA00029243 ACCEPT general (21-200) 73 human/MTHFD1 GO:0046655 folic acid metabolic process ARBA:ARBA00091997 KEEP_AS_NON_CORE specific (1-20) 2 human/MTHFD1L GO:0005759 mitochondrial matrix ARBA:ARBA00028628 ACCEPT specific (1-20) 17 human/MTHFD1L GO:0015942 formate metabolic process ARBA:ARBA00088783 ACCEPT specific (1-20) 4 human/MTHFD1L GO:0046394 carboxylic acid biosynthetic process ARBA:ARBA00027883 MARK_AS_OVER_ANNOTATED very general (>200 descendants) 208 TOO_GENERAL true but uninformative high-level Too high-level to be informative; the specific formate metabolic process and tetrahydrofolate interconversion terms convey the relevant biology. human/MTHFD1L GO:0046653 tetrahydrofolate metabolic process ARBA:ARBA00033901 KEEP_AS_NON_CORE specific (1-20) 5 human/MTHFD2 GO:0005759 mitochondrial matrix ARBA:ARBA00028628 ACCEPT specific (1-20) 17 human/MTHFD2 GO:0046655 folic acid metabolic process ARBA:ARBA00091997 KEEP_AS_NON_CORE specific (1-20) 2 human/MTMR9 GO:0005829 cytosol ARBA:ARBA00029243 ACCEPT general (21-200) 73 human/MTRR GO:0009235 cobalamin metabolic process ARBA:ARBA00090606 ACCEPT specific (1-20) 2 human/MTRR GO:0046655 folic acid metabolic process ARBA:ARBA00091997 ACCEPT specific (1-20) 2 human/MTRR GO:0050667 homocysteine metabolic process ARBA:ARBA00089512 ACCEPT specific (1-20) 4 human/MTRR GO:0170033 obsolete L-amino acid metabolic process ARBA:ARBA00044572 REMOVE leaf (0) 0 OBSOLETE_OR_PSEUDOGENE wrong manual OBSOLETE_OR_PSEUDOGENE The term is obsolete and uninformatively broad; the specific L-methionine biosynthetic process (GO:0071265) and homocysteine annotations already capture the relevant biology. This over-propagated electronic annotation should be dropped. human/MVB12B GO:0005737 cytoplasm ARBA:ARBA00026971 KEEP_AS_NON_CORE very general (>200 descendants) 1146 human/MVK GO:0016125 sterol metabolic process ARBA:ARBA00034378 KEEP_AS_NON_CORE specific (1-20) 13 human/MYD88 GO:0005126 cytokine receptor binding ARBA:ARBA00027199 MODIFY general (21-200) 91 NEEDS_MORE_SPECIFIC true but uninformative replacement term Correct in spirit (IL-1R, IL-18R and IL-33R are cytokine receptors) but less specific than GO:0005149, which is supported experimentally. human/MYD88 GO:0009617 response to bacterium ARBA:ARBA00026494 KEEP_AS_NON_CORE general (21-200) 53 human/MYH10 GO:0031032 actomyosin structure organization ARBA:ARBA00084739 ACCEPT general (21-200) 30 human/MYH10 GO:0042641 actomyosin ARBA:ARBA00086793 ACCEPT specific (1-20) 2 human/MYH10 GO:0097513 myosin II filament ARBA:ARBA00098384 ACCEPT leaf (0) 0 human/MYH10 GO:0098794 postsynapse ARBA:ARBA00028832 KEEP_AS_NON_CORE general (21-200) 50 human/MYH9 GO:0032970 regulation of actin filament-based process ARBA:ARBA00028754 KEEP_AS_NON_CORE general (21-200) 86 human/MYH9 GO:0072359 circulatory system development ARBA:ARBA00027039 KEEP_AS_NON_CORE very general (>200 descendants) 399 human/MYH9 GO:0099512 supramolecular fiber ARBA:ARBA00026673 ACCEPT general (21-200) 80 human/MYL10 GO:0005829 cytosol ARBA:ARBA00029243 KEEP_AS_NON_CORE general (21-200) 73 human/MYO5A GO:0003824 catalytic activity ARBA:ARBA00027533 MODIFY very general (>200 descendants) 6405 NEEDS_MORE_SPECIFIC true but uninformative replacement term Uninformative root-level term; the catalytic activity of the myosin motor domain is ATP hydrolysis coupled to movement on actin. human/MYO5A GO:0015629 actin cytoskeleton ARBA:ARBA00029230 ACCEPT general (21-200) 89 human/MYO5A GO:0030048 actin filament-based movement ARBA:ARBA00028189 ACCEPT general (21-200) 26 human/MYO5A GO:0031267 small GTPase binding ARBA:ARBA00029074 ACCEPT leaf (0) 0 human/MYO5A GO:0051650 establishment of vesicle localization ARBA:ARBA00033964 ACCEPT general (21-200) 39 human/MYO7A GO:0000146 microfilament motor activity ARBA:ARBA00090457 ACCEPT specific (1-20) 2 human/MYO7A GO:0005829 cytosol ARBA:ARBA00029243 KEEP_AS_NON_CORE general (21-200) 73 human/MYO7A GO:0007040 lysosome organization ARBA:ARBA00033903 MODIFY specific (1-20) 6 OTHER_TERM different term needed replacement term The underlying biology, RPE phagosome and lysosome positioning and digestion, is real, but the process MYO7A performs is positioning and transport of the organelle rather than lysosome biogenesis or the arrangement of its constituent parts. GO:0032418 lysosome localization is the accurate term, as proposed for the corresponding IDA. human/MYO7A GO:0007601 visual perception ARBA:ARBA00086021 ACCEPT specific (1-20) 1 human/MYO7A GO:0007605 sensory perception of sound ARBA:ARBA00033578 ACCEPT specific (1-20) 2 human/MYO7A GO:0008092 cytoskeletal protein binding ARBA:ARBA00029239 ACCEPT general (21-200) 53 human/MYO7A GO:0016020 membrane ARBA:ARBA00028763 KEEP_AS_NON_CORE very general (>200 descendants) 895 human/MYO7A GO:0030048 actin filament-based movement ARBA:ARBA00028189 ACCEPT general (21-200) 26 human/MYO7A GO:0048666 neuron development ARBA:ARBA00028378 MARK_AS_OVER_ANNOTATED general (21-200) 186 TOO_GENERAL true but uninformative general The two cell types where MYO7A function is established are cochlear and vestibular hair cells, which are mechanosensory epithelial cells and not neurons, and photoreceptors, where the motor acts in transport and maintenance of an already differentiated cell rather than in its development. The term is not strictly false, since photoreceptors are neurons, but it generalises well beyond what the evidence shows, so it is flagged as an over-annotation rather than kept as a substantive process. human/MYO7A GO:0090596 sensory organ morphogenesis ARBA:ARBA00043576 KEEP_AS_NON_CORE general (21-200) 116 human/MYO7A GO:0097733 photoreceptor cell cilium ARBA:ARBA00026421 ACCEPT specific (1-20) 12 human/NAA15 GO:0031415 NatA complex ARBA:ARBA00085755 ACCEPT leaf (0) 0 human/NAA15 GO:0043022 ribosome binding ARBA:ARBA00084665 ACCEPT specific (1-20) 5 human/NAA30 GO:0031417 NatC complex ARBA:ARBA00085759 ACCEPT leaf (0) 0 human/NADK2 GO:0005759 mitochondrial matrix ARBA:ARBA00028628 ACCEPT specific (1-20) 17 human/NADSYN1 GO:0005829 cytosol ARBA:ARBA00029243 ACCEPT general (21-200) 73 human/NADSYN1 GO:0034354 'de novo' NAD+ biosynthetic process from L-tryptophan ARBA:ARBA00093758 ACCEPT leaf (0) 0 human/NAGK GO:0006044 N-acetylglucosamine metabolic process ARBA:ARBA00084676 ACCEPT specific (1-20) 2 human/NAGLU GO:0048731 system development ARBA:ARBA00027702 MARK_AS_OVER_ANNOTATED very general (>200 descendants) 2438 INDIRECT_EFFECT overreach phenotype This general developmental term reflects the disease phenotype (multi-system, predominantly neurological deterioration in MPS IIIB) rather than a direct developmental role of the enzyme. The observed developmental defects are downstream consequences of impaired heparan sulfate catabolism and lysosomal storage, not a molecular developmental function of NAGLU. Uninformative at this level and over-annotated. human/NAGLU GO:1901135 carbohydrate derivative metabolic process ARBA:ARBA00026297 MODIFY very general (>200 descendants) 637 NEEDS_MORE_SPECIFIC true but uninformative replacement term NAGLU does act in the metabolism of a carbohydrate derivative (heparan sulfate, an N-acetylglucosamine-containing glycosaminoglycan), so the term is not incorrect, but it is far too general to be informative. Modify to the specific heparan sulfate proteoglycan catabolic process that captures the actual biology. human/NANP GO:0006054 N-acetylneuraminate metabolic process ARBA:ARBA00084579 KEEP_AS_NON_CORE specific (1-20) 2 human/NANS GO:0006054 N-acetylneuraminate metabolic process ARBA:ARBA00084579 KEEP_AS_NON_CORE specific (1-20) 2 human/NAT10 GO:0140640 catalytic activity, acting on a nucleic acid ARBA:ARBA00026869 MODIFY very general (>200 descendants) 444 NEEDS_MORE_SPECIFIC true but uninformative replacement term True but essentially contentless for a protein with a precisely defined catalytic activity. human/NBR1 GO:0005778 peroxisomal membrane ARBA:ARBA00028584 KEEP_AS_NON_CORE specific (1-20) 3 human/NCSTN GO:0012505 endomembrane system ARBA:ARBA00028953 ACCEPT very general (>200 descendants) 357 human/NCSTN GO:0099503 secretory vesicle ARBA:ARBA00026625 ACCEPT general (21-200) 68 human/NDUFA2 GO:0005739 mitochondrion ARBA:ARBA00026962 KEEP_AS_NON_CORE general (21-200) 70 human/NDUFAF5 GO:0005739 mitochondrion ARBA:ARBA00026962 ACCEPT general (21-200) 70 human/NDUFAF5 GO:0032981 mitochondrial respiratory chain complex I assembly ARBA:ARBA00087368 ACCEPT leaf (0) 0 human/NDUFAF7 GO:0032981 mitochondrial respiratory chain complex I assembly ARBA:ARBA00087368 ACCEPT leaf (0) 0 human/NDUFB10 GO:0005739 mitochondrion ARBA:ARBA00026962 KEEP_AS_NON_CORE general (21-200) 70 human/NDUFS3 GO:0006120 mitochondrial electron transport, NADH to ubiquinone ARBA:ARBA00084241 ACCEPT leaf (0) 0 human/NDUFS3 GO:0045271 respiratory chain complex I ARBA:ARBA00027636 ACCEPT leaf (0) 0 human/NDUFS4 GO:0045271 respiratory chain complex I ARBA:ARBA00027636 ACCEPT leaf (0) 0 human/NDUFS4 GO:0072593 reactive oxygen species metabolic process ARBA:ARBA00028586 KEEP_AS_NON_CORE specific (1-20) 11 human/NDUFS6 GO:0005739 mitochondrion ARBA:ARBA00026962 KEEP_AS_NON_CORE general (21-200) 70 human/NEURL1 GO:0010646 regulation of cell communication ARBA:ARBA00026589 MARK_AS_OVER_ANNOTATED very general (>200 descendants) 964 TOO_GENERAL true but uninformative Uninformative Uninformative high-level terms. human/NEURL1 GO:0023051 regulation of signaling ARBA:ARBA00026307 MARK_AS_OVER_ANNOTATED very general (>200 descendants) 944 TOO_GENERAL true but uninformative Uninformative Uninformative high-level terms. human/NEURL1 GO:0160108 animal gross anatomical part developmental process ARBA:ARBA00098139 MARK_AS_OVER_ANNOTATED very general (>200 descendants) 3010 TOO_GENERAL true but uninformative Uninformative Uninformative high-level terms. human/NEUROD1 GO:1990837 sequence-specific double-stranded DNA binding ARBA:ARBA00028376 ACCEPT general (21-200) 48 human/NEUROG1 GO:1990837 sequence-specific double-stranded DNA binding ARBA:ARBA00028376 ACCEPT general (21-200) 48 human/NEUROG2 GO:1990837 sequence-specific double-stranded DNA binding ARBA:ARBA00028376 ACCEPT general (21-200) 48 human/NF1 GO:0050793 regulation of developmental process ARBA:ARBA00028689 KEEP_AS_NON_CORE very general (>200 descendants) 1542 human/NFATC1 GO:1990837 sequence-specific double-stranded DNA binding ARBA:ARBA00028376 ACCEPT general (21-200) 48 human/NFIA GO:0045893 positive regulation of DNA-templated transcription ARBA:ARBA00029082 ACCEPT general (21-200) 42 human/NID1 GO:0005576 extracellular region ARBA:ARBA00027128 ACCEPT very general (>200 descendants) 276 human/NID1 GO:0043236 laminin binding ARBA:ARBA00086571 ACCEPT specific (1-20) 2 human/NID1 GO:0071711 basement membrane organization ARBA:ARBA00085295 ACCEPT specific (1-20) 3 human/NLRP3 GO:0009595 detection of biotic stimulus ARBA:ARBA00034390 KEEP_AS_NON_CORE general (21-200) 32 human/NLRP3 GO:0009615 response to virus ARBA:ARBA00026492 KEEP_AS_NON_CORE specific (1-20) 9 human/NLRP3 GO:0016887 ATP hydrolysis activity ARBA:ARBA00043426 ACCEPT leaf (0) 0 human/NLRP3 GO:0032731 positive regulation of interleukin-1 beta production ARBA:ARBA00033916 ACCEPT leaf (0) 0 human/NLRP3 GO:0035591 signaling adaptor activity ARBA:ARBA00090724 ACCEPT specific (1-20) 5 human/NLRP3 GO:0044546 NLRP3 inflammasome complex assembly ARBA:ARBA00086550 ACCEPT leaf (0) 0 human/NLRP3 GO:0050729 positive regulation of inflammatory response ARBA:ARBA00045046 ACCEPT general (21-200) 30 human/NLRP3 GO:0051260 protein homooligomerization ARBA:ARBA00089314 ACCEPT specific (1-20) 2 human/NLRP3 GO:0070273 phosphatidylinositol-4-phosphate binding ARBA:ARBA00091843 ACCEPT leaf (0) 0 human/NLRP3 GO:0071222 cellular response to lipopolysaccharide ARBA:ARBA00092913 ACCEPT specific (1-20) 3 human/NLRP3 GO:0072559 NLRP3 inflammasome complex ARBA:ARBA00092912 ACCEPT leaf (0) 0 human/NLRP3 GO:0140299 molecular sensor activity ARBA:ARBA00026335 MARK_AS_OVER_ANNOTATED general (21-200) 27 INDIRECT_EFFECT overreach downstream The biology is right but the term is not. GO:0140299 is defined as 'Binding to a molecule and eliciting a change in the protein's activity in response to the intracellular level of that molecule' - it requires that the sensed species be bound. No direct NLRP3 agonist ligand has ever been identified, and the three papers cited here argue the opposite of direct binding: Hornung et al. state that activation required phagocytosis of crystals leading to lysosomal damage and rupture, and conclude that NLRP3 senses lysosomal damage as an endogenous danger signal. The field position is that NLRP3 reads a shared downstream cellular perturbation - potassium efflux, trans-Golgi disassembly, organelle damage - common to structurally unrelated agonists. Flagged as over-annotated rather than removed, because these are experimental annotations recording real activation events and because one NLRP3 binding event does fit the definition: PtdIns4P on the dispersed TGN, which is separately and correctly annotated as GO:0070273. human/NME2 GO:0009142 nucleoside triphosphate biosynthetic process ARBA:ARBA00033837 ACCEPT specific (1-20) 12 human/NMNAT1 GO:0006163 purine nucleotide metabolic process ARBA:ARBA00026737 MARK_AS_OVER_ANNOTATED general (21-200) 130 TOO_GENERAL true but uninformative broad ARBA electronic annotation. NMNAT1 consumes ATP as an adenylyl donor, but its biological role is NAD+ (pyridine nucleotide) biosynthesis, not purine nucleotide metabolism. This term is over-broad and tangential; the pyridine nucleotide / NAD biosynthesis terms capture the true process. human/NMNAT1 GO:0009165 nucleotide biosynthetic process ARBA:ARBA00027613 KEEP_AS_NON_CORE general (21-200) 114 human/NMNAT2 GO:0009165 nucleotide biosynthetic process ARBA:ARBA00027613 MARK_AS_OVER_ANNOTATED general (21-200) 114 TOO_GENERAL true but uninformative General General nucleotide biosynthetic process assigned by an ARBA machine-learning model. True but much less informative than the specific NAD+ biosynthetic process (GO:0009435) and its salvage child, which are also annotated. Kept as a correct high-level parent. human/NMNAT3 GO:0005759 mitochondrial matrix ARBA:ARBA00028628 ACCEPT specific (1-20) 17 human/NMNAT3 GO:0009165 nucleotide biosynthetic process ARBA:ARBA00027613 MARK_AS_OVER_ANNOTATED general (21-200) 114 TOO_GENERAL true but uninformative general Correct but over-general parent of NAD+ biosynthetic process. The specific terms GO:0009435 / GO:0034355 are annotated and preferred. Over-annotation of a broad parent. human/NMRK1 GO:0005829 cytosol ARBA:ARBA00029243 ACCEPT general (21-200) 73 human/NMRK1 GO:1901847 nicotinate metabolic process ARBA:ARBA00091463 KEEP_AS_NON_CORE specific (1-20) 2 human/NMRK2 GO:0005829 cytosol ARBA:ARBA00029243 ACCEPT general (21-200) 73 human/NMRK2 GO:1901847 nicotinate metabolic process ARBA:ARBA00091463 KEEP_AS_NON_CORE specific (1-20) 2 human/NOTCH1 GO:0000139 Golgi membrane ARBA:ARBA00029253 ACCEPT specific (1-20) 6 human/NOTCH1 GO:0005789 endoplasmic reticulum membrane ARBA:ARBA00028685 ACCEPT general (21-200) 54 human/NOTCH1 GO:0045893 positive regulation of DNA-templated transcription ARBA:ARBA00029082 ACCEPT general (21-200) 42 human/NOTCH1 GO:0046579 positive regulation of Ras protein signal transduction ARBA:ARBA00092483 KEEP_AS_NON_CORE leaf (0) 0 human/NOTCH1 GO:0051152 positive regulation of smooth muscle cell differentiation ARBA:ARBA00087721 KEEP_AS_NON_CORE specific (1-20) 5 human/NOTCH1 GO:0070374 positive regulation of ERK1 and ERK2 cascade ARBA:ARBA00085202 KEEP_AS_NON_CORE leaf (0) 0 human/NOTCH1 GO:0071228 cellular response to tumor cell ARBA:ARBA00092915 KEEP_AS_NON_CORE leaf (0) 0 human/NOVA2 GO:1990825 sequence-specific mRNA binding ARBA:ARBA00089164 ACCEPT specific (1-20) 1 human/NPHP1 GO:0005737 cytoplasm ARBA:ARBA00026971 ACCEPT very general (>200 descendants) 1146 human/NPLOC4 GO:0030970 retrograde protein transport, ER to cytosol ARBA:ARBA00087984 ACCEPT leaf (0) 0 human/NPM1 GO:0010604 positive regulation of macromolecule metabolic process ARBA:ARBA00026482 MARK_AS_OVER_ANNOTATED very general (>200 descendants) 467 TOO_GENERAL true but uninformative broad While technically correct, this is an extremely broad term that adds no informative value beyond what is captured by more specific annotations for ribosome biogenesis and transcription regulation. human/NPM1 GO:0042127 regulation of cell population proliferation ARBA:ARBA00027546 KEEP_AS_NON_CORE very general (>200 descendants) 258 human/NPM1 GO:0042254 ribosome biogenesis ARBA:ARBA00026817 ACCEPT general (21-200) 78 human/NPM1 GO:0043066 negative regulation of apoptotic process ARBA:ARBA00027746 KEEP_AS_NON_CORE general (21-200) 79 human/NRAS GO:0000165 MAPK cascade ARBA:ARBA00029221 ACCEPT specific (1-20) 18 human/NRXN1 GO:0007158 neuron cell-cell adhesion ARBA:ARBA00085299 MODIFY leaf (0) 0 OTHER_TERM different term needed replacement term Correct in essence: neurexins mediate adhesion between neurons by binding postsynaptic partners across the synaptic cleft. The adhesion is specifically between pre- and postsynaptic membranes, so the precise process is GO:0099560 synaptic membrane adhesion, as for the TAS row. human/NRXN1 GO:0030534 adult behavior ARBA:ARBA00086959 KEEP_AS_NON_CORE specific (1-20) 10 human/NRXN1 GO:0035176 social behavior ARBA:ARBA00091504 KEEP_AS_NON_CORE specific (1-20) 2 human/NRXN1 GO:0042297 vocal learning ARBA:ARBA00085667 MARK_AS_OVER_ANNOTATED leaf (0) 0 UNCLASSIFIED unclassified The only experimental support is clinical absence of speech in patients with severe intellectual disability, which does not show that NRXN1 acts in vocalization per se. The rule-based transfer inherits this over-interpretation. human/NRXN1 GO:0071625 vocalization behavior ARBA:ARBA00092174 MARK_AS_OVER_ANNOTATED specific (1-20) 2 UNCLASSIFIED unclassified The only experimental support is clinical absence of speech in patients with severe intellectual disability, which does not show that NRXN1 acts in vocalization per se. The rule-based transfer inherits this over-interpretation. human/NRXN2 GO:0007158 neuron cell-cell adhesion ARBA:ARBA00085299 MODIFY leaf (0) 0 OTHER_TERM different term needed replacement term Correct in essence: neurexin-2 mediates adhesion between neurons by binding postsynaptic partners across the synaptic cleft (neurexin-2-beta-expressing cells aggregate with latrophilin-1-expressing cells; IgSF21 recruits axonal neurexin-2-alpha in trans). The adhesion is specifically between pre- and postsynaptic membranes, so the precise process is GO:0099560 synaptic membrane adhesion, as chosen for NRXN1. human/NRXN2 GO:0030534 adult behavior ARBA:ARBA00086959 KEEP_AS_NON_CORE specific (1-20) 10 human/NRXN2 GO:0035176 social behavior ARBA:ARBA00091504 KEEP_AS_NON_CORE specific (1-20) 2 human/NRXN2 GO:0042297 vocal learning ARBA:ARBA00085667 MARK_AS_OVER_ANNOTATED leaf (0) 0 INDIRECT_EFFECT overreach phenotype The only support is that one autistic proband's carrier father had severe language delay. Language delay in an autism/neurodevelopmental context does not show that NRXN2 acts in vocal learning or vocalization per se, and no NRXN2 mouse study reports a specific vocalization phenotype. Over-interpretation of a clinical feature, as for NRXN1. human/NRXN2 GO:0071625 vocalization behavior ARBA:ARBA00092174 MARK_AS_OVER_ANNOTATED specific (1-20) 2 INDIRECT_EFFECT overreach phenotype The only support is that one autistic proband's carrier father had severe language delay. Language delay in an autism/neurodevelopmental context does not show that NRXN2 acts in vocal learning or vocalization per se, and no NRXN2 mouse study reports a specific vocalization phenotype. Over-interpretation of a clinical feature, as for NRXN1. human/NRXN3 GO:0007158 neuron cell-cell adhesion ARBA:ARBA00085299 MODIFY leaf (0) 0 OTHER_TERM different term needed replacement term Correct in essence: neurexin-3 mediates adhesion between neurons by binding postsynaptic partners across the synaptic cleft (neurexin-3-beta-expressing cells aggregate with latrophilin-1-expressing cells; neurexin-3-alpha cells aggregate with neuroligin- and LRRTM2-expressing cells). The adhesion is specifically between pre- and postsynaptic membranes, so the precise process is GO:0099560 synaptic membrane adhesion, as chosen for NRXN1 and NRXN2. human/NRXN3 GO:0007399 nervous system development ARBA:ARBA00027428 KEEP_AS_NON_CORE very general (>200 descendants) 913 human/NRXN3 GO:0007612 learning ARBA:ARBA00086033 KEEP_AS_NON_CORE specific (1-20) 14 human/NRXN3 GO:0030534 adult behavior ARBA:ARBA00086959 KEEP_AS_NON_CORE specific (1-20) 10 human/NRXN3 GO:0035176 social behavior ARBA:ARBA00091504 KEEP_AS_NON_CORE specific (1-20) 2 human/NRXN3 GO:0071625 vocalization behavior ARBA:ARBA00092174 MARK_AS_OVER_ANNOTATED specific (1-20) 2 INDIRECT_EFFECT overreach phenotype The ASD CNV paper reports speech-language delay in one proband, who later had near-normal speech, and auditory/language-processing difficulties self-reported by a carrier mother. Language delay as part of an autism diagnosis does not show that NRXN3 acts in vocalization (sound production) per se, and no NRXN3 study reports a specific vocalization phenotype in mice. Over-interpretation of a clinical feature, treated as for NRXN1 and NRXN2. human/NSUN2 GO:0006397 mRNA processing ARBA:ARBA00028222 MODIFY general (21-200) 36 OTHER_TERM different term needed replacement term A term-choice problem rather than an evidence problem, so the annotations are modified rather than removed. PMID:22395603 reports that NSUN2 inhibits turnover of p16 mRNA, PMID:31358969 that NSUN2 with YBX1 stabilises HDGF mRNA, and PMID:28418038 that NSUN2-dependent m5C promotes ALYREF-mediated nuclear export. None of these is a pre-mRNA maturation step. The accurate terms are mRNA stabilization (GO:0048255) and regulation of mRNA export from nucleus (GO:0010793), the latter of which this gene already carries from PMID:28418038. human/NSUN2 GO:0030488 tRNA methylation ARBA:ARBA00028068 ACCEPT specific (1-20) 16 human/NT5C2 GO:0046054 dGMP metabolic process ARBA:ARBA00090848 KEEP_AS_NON_CORE specific (1-20) 3 human/NT5C3A GO:0005829 cytosol ARBA:ARBA00029243 ACCEPT general (21-200) 73 human/NT5E GO:0016020 membrane ARBA:ARBA00028763 MARK_AS_OVER_ANNOTATED very general (>200 descendants) 895 TOO_GENERAL true but uninformative generic ARBA electronic annotation to the generic parent term membrane. Correct but uninformative given the specific plasma-membrane / external-side-of-plasma-membrane localization. Mark as over-annotation. human/NTN3 GO:0005737 cytoplasm ARBA:ARBA00026971 KEEP_AS_NON_CORE very general (>200 descendants) 1146 human/NTN3 GO:0007409 axonogenesis ARBA:ARBA00026520 ACCEPT general (21-200) 78 human/NUBPL GO:0005759 mitochondrial matrix ARBA:ARBA00028628 ACCEPT specific (1-20) 17 human/NUBPL GO:0032981 mitochondrial respiratory chain complex I assembly ARBA:ARBA00087368 ACCEPT leaf (0) 0 human/NUS1 GO:0004659 prenyltransferase activity ARBA:ARBA00027066 MODIFY general (21-200) 39 NEEDS_MORE_SPECIFIC true but uninformative replacement term ARBA electronic annotation to the broad parent term prenyltransferase activity. NUS1 does not independently have prenyltransferase activity; it contributes to the complex-level cis-PT activity via its RXG motif. The specific cis-PT activity term GO:0045547, used with contributes_to, captures this more accurately. Modify to the specific term. human/NUS1 GO:0009101 glycoprotein biosynthetic process ARBA:ARBA00027560 KEEP_AS_NON_CORE general (21-200) 37 human/NUS1 GO:0016020 membrane ARBA:ARBA00028763 MARK_AS_OVER_ANNOTATED very general (>200 descendants) 895 TOO_GENERAL true but uninformative general ARBA electronic annotation to the very general term membrane. NUS1 is indeed a membrane protein, but this is uninformative given the specific ER-membrane annotations already present. Over-annotated (too general). human/NUS1 GO:0032383 regulation of intracellular cholesterol transport ARBA:ARBA00084709 KEEP_AS_NON_CORE specific (1-20) 4 human/OAT GO:0008483 transaminase activity ARBA:ARBA00028950 MARK_AS_OVER_ANNOTATED general (21-200) 91 TOO_GENERAL true but uninformative general ARBA electronic assignment of the general transaminase activity. This is a parent of the specific and experimentally supported ornithine aminotransferase activity (GO:0004587) and adds no information beyond it. Over-annotated (too general). human/OAZ1 GO:0006576 biogenic amine metabolic process ARBA:ARBA00026437 MARK_AS_OVER_ANNOTATED general (21-200) 47 TOO_GENERAL true but uninformative broad Electronic ARBA annotation to the broad parent 'biogenic amine metabolic process'. Polyamine metabolism is a subclass of biogenic amine metabolism, so this is not wrong, but it is far too general and adds no information beyond the specific polyamine-regulation annotations. Over-annotated. human/ODC1 GO:0006595 polyamine metabolic process ARBA:ARBA00026605 KEEP_AS_NON_CORE specific (1-20) 18 human/OLIG2 GO:1990837 sequence-specific double-stranded DNA binding ARBA:ARBA00028376 ACCEPT general (21-200) 48 human/OPA1 GO:0007005 mitochondrion organization ARBA:ARBA00026723 ACCEPT general (21-200) 37 human/OPA1 GO:0010821 regulation of mitochondrion organization ARBA:ARBA00084914 KEEP_AS_NON_CORE specific (1-20) 17 human/OPTN GO:0005737 cytoplasm ARBA:ARBA00026971 KEEP_AS_NON_CORE very general (>200 descendants) 1146 human/ORMDL3 GO:0006665 sphingolipid metabolic process ARBA:ARBA00028658 ACCEPT general (21-200) 47 human/ORMDL3 GO:2000303 regulation of ceramide biosynthetic process ARBA:ARBA00027641 ACCEPT specific (1-20) 5 human/OTC GO:0005739 mitochondrion ARBA:ARBA00026962 ACCEPT general (21-200) 70 human/OTUD3 GO:0016579 protein deubiquitination ARBA:ARBA00027879 ACCEPT specific (1-20) 10 human/P2RX7 GO:0015748 organophosphate ester transport ARBA:ARBA00028511 MARK_AS_OVER_ANNOTATED general (21-200) 166 UNCLASSIFIED unclassified P2X7 binds ATP on the outside of the cell and opens a cation channel; it does not translocate ATP or other organophosphate esters across the membrane. The large-solute permeability that could motivate such a term was attributed to pannexin-1, and single-channel analysis argued against dilation of the P2X7 pore itself. This is a rule-based over-reach from the ligand to a transport activity. human/P2RX7 GO:0032060 bleb assembly ARBA:ARBA00092098 KEEP_AS_NON_CORE leaf (0) 0 human/P2RX7 GO:0032731 positive regulation of interleukin-1 beta production ARBA:ARBA00033916 ACCEPT leaf (0) 0 human/P2RX7 GO:0046931 pore complex assembly ARBA:ARBA00084490 KEEP_AS_NON_CORE specific (1-20) 2 human/P2RX7 GO:0051049 regulation of transport ARBA:ARBA00027251 MODIFY very general (>200 descendants) 960 NEEDS_MORE_SPECIFIC true but uninformative replacement term ARBA rule-based transfer of a term so general it excludes almost nothing. The specific regulatory relationship this gene has evidence for is already annotated. human/P2RX7 GO:0051130 positive regulation of cellular component organization ARBA:ARBA00026675 MODIFY very general (>200 descendants) 291 NEEDS_MORE_SPECIFIC true but uninformative replacement term ARBA rule-based transfer. The cellular component organisation that P2X7 actually promotes is membrane blebbing, which this gene already carries with IMP support. human/P4HB GO:0034975 protein folding in endoplasmic reticulum ARBA:ARBA00084679 KEEP_AS_NON_CORE leaf (0) 0 human/PAFAH1B1 GO:0030900 forebrain development ARBA:ARBA00088344 KEEP_AS_NON_CORE general (21-200) 165 human/PAM16 GO:0001405 PAM complex, Tim23 associated import motor ARBA:ARBA00090373 ACCEPT leaf (0) 0 human/PANK2 GO:0005829 cytosol ARBA:ARBA00029243 KEEP_AS_NON_CORE general (21-200) 73 human/PAPSS1 GO:0005737 cytoplasm ARBA:ARBA00026971 MODIFY very general (>200 descendants) 1146 NEEDS_MORE_SPECIFIC true but uninformative replacement term Correct but less specific than the experimentally supported cytosol (GO:0005829) annotation. Generalized cytoplasm term; MODIFY to cytosol. human/PAPSS1 GO:0050428 3'-phosphoadenosine 5'-phosphosulfate biosynthetic process ARBA:ARBA00089999 ACCEPT leaf (0) 0 human/PAPSS2 GO:0050428 3'-phosphoadenosine 5'-phosphosulfate biosynthetic process ARBA:ARBA00089999 ACCEPT leaf (0) 0 human/PAX6 GO:0007417 central nervous system development ARBA:ARBA00026561 KEEP_AS_NON_CORE very general (>200 descendants) 464 human/PAX6 GO:0009653 anatomical structure morphogenesis ARBA:ARBA00026583 MARK_AS_OVER_ANNOTATED very general (>200 descendants) 1501 TOO_GENERAL true but uninformative high-level The essence (PAX6 drives morphogenesis) is correct, but this high-level term adds little beyond the more specific eye/brain/iris/cornea morphogenesis annotations already present. human/PAX6 GO:0043010 camera-type eye development ARBA:ARBA00084629 KEEP_AS_NON_CORE general (21-200) 60 human/PAX6 GO:0045944 positive regulation of transcription by RNA polymerase II ARBA:ARBA00027996 ACCEPT specific (1-20) 12 human/PAX6 GO:0050877 nervous system process ARBA:ARBA00029146 REMOVE general (21-200) 194 TERM_MISREAD wrong manual TERM_MISREAD This term denotes ongoing physiological functioning of the nervous system rather than development. PAX6's nervous-system roles are developmental (already captured by CNS/forebrain development terms). No evidence supports a direct nervous system process function; likely an over-broad electronic mis-mapping. human/PC GO:0005829 cytosol ARBA:ARBA00029243 KEEP_AS_NON_CORE general (21-200) 73 human/PC GO:0009374 biotin binding ARBA:ARBA00093012 ACCEPT leaf (0) 0 human/PCCA GO:0009374 biotin binding ARBA:ARBA00093012 ACCEPT leaf (0) 0 human/PCCA GO:0016885 ligase activity, forming carbon-carbon bonds ARBA:ARBA00028615 ACCEPT specific (1-20) 8 human/PCCB GO:0009062 fatty acid catabolic process ARBA:ARBA00028514 KEEP_AS_NON_CORE specific (1-20) 17 human/PCYT1A GO:0046470 phosphatidylcholine metabolic process ARBA:ARBA00028347 MODIFY specific (1-20) 6 NEEDS_MORE_SPECIFIC true but uninformative replacement term Over-general; replace with the specific biosynthetic process. human/PCYT1B GO:0046470 phosphatidylcholine metabolic process ARBA:ARBA00028347 KEEP_AS_NON_CORE specific (1-20) 6 human/PDCD6IP GO:0005737 cytoplasm ARBA:ARBA00026971 KEEP_AS_NON_CORE very general (>200 descendants) 1146 human/PDGFA GO:0008284 positive regulation of cell population proliferation ARBA:ARBA00027538 ACCEPT general (21-200) 85 human/PDGFA GO:0048018 receptor ligand activity ARBA:ARBA00028558 ACCEPT general (21-200) 34 human/PDGFB GO:0007169 cell surface receptor protein tyrosine kinase signaling pathway ARBA:ARBA00029045 MODIFY general (21-200) 75 NEEDS_MORE_SPECIFIC true but uninformative replacement term The parent receptor tyrosine kinase signaling term is directionally correct but too broad. PDGFB specifically initiates platelet-derived growth factor receptor signaling. human/PDGFB GO:0010468 regulation of gene expression ARBA:ARBA00028334 MARK_AS_OVER_ANNOTATED very general (>200 descendants) 874 INDIRECT_EFFECT overreach downstream Regulation of gene expression is a broad downstream response to PDGF signaling and should not be treated as a PDGFB core function. human/PDGFB GO:0010557 positive regulation of macromolecule biosynthetic process ARBA:ARBA00027412 KEEP_AS_NON_CORE very general (>200 descendants) 270 human/PDGFB GO:0014911 positive regulation of smooth muscle cell migration ARBA:ARBA00089842 ACCEPT specific (1-20) 2 human/PDGFB GO:0048018 receptor ligand activity ARBA:ARBA00028558 ACCEPT general (21-200) 34 human/PDGFB GO:0048661 positive regulation of smooth muscle cell proliferation ARBA:ARBA00091355 ACCEPT specific (1-20) 1 human/PDGFB GO:0051239 regulation of multicellular organismal process ARBA:ARBA00028859 KEEP_AS_NON_CORE very general (>200 descendants) 1807 human/PDGFB GO:1902533 positive regulation of intracellular signal transduction ARBA:ARBA00027124 MARK_AS_OVER_ANNOTATED general (21-200) 89 INDIRECT_EFFECT overreach downstream Positive regulation of intracellular signal transduction is too broad and downstream for the extracellular PDGFB ligand. human/PDHA1 GO:0045254 pyruvate dehydrogenase complex ARBA:ARBA00092491 ACCEPT leaf (0) 0 human/PDHX GO:0004742 dihydrolipoyllysine-residue acetyltransferase activity ARBA:ARBA00095301 MARK_AS_OVER_ANNOTATED leaf (0) 0 NONCATALYTIC wrong lacks the catalytic PDHX retains the E2-like inner-core fold (hence the ARBA family mapping) but lacks the catalytic histidine required for transacetylase activity; it is a structural/E3-anchoring subunit, not a catalytic acyltransferase. The annotation reflects fold similarity, not true molecular function. human/PDSS1 GO:0005759 mitochondrial matrix ARBA:ARBA00028628 KEEP_AS_NON_CORE specific (1-20) 17 human/PDSS2 GO:0006629 lipid metabolic process ARBA:ARBA00028591 MARK_AS_OVER_ANNOTATED very general (>200 descendants) 608 TOO_GENERAL true but uninformative general Overly general ancestor term superseded by the specific ubiquinone biosynthetic process annotation. human/PDXK GO:0042816 vitamin B6 metabolic process ARBA:ARBA00027956 KEEP_AS_NON_CORE specific (1-20) 13 human/PDZD7 GO:0120025 plasma membrane bounded cell projection ARBA:ARBA00028036 KEEP_AS_NON_CORE very general (>200 descendants) 303 human/PEA15 GO:1902042 negative regulation of extrinsic apoptotic signaling pathway via death domain receptors ARBA:ARBA00088654 ACCEPT specific (1-20) 1 human/PEX1 GO:0044877 protein-containing complex binding ARBA:ARBA00026521 ACCEPT general (21-200) 108 human/PEX12 GO:0007031 peroxisome organization ARBA:ARBA00026708 ACCEPT specific (1-20) 15 human/PEX19 GO:0016020 membrane ARBA:ARBA00028763 ACCEPT very general (>200 descendants) 895 human/PEX6 GO:0044877 protein-containing complex binding ARBA:ARBA00026521 ACCEPT general (21-200) 108 human/PFDN1 GO:0032991 protein-containing complex ARBA:ARBA00028902 MARK_AS_OVER_ANNOTATED very general (>200 descendants) 2083 TOO_GENERAL true but uninformative general "This is an overly general annotation. PFDN1 is part of the prefoldin complex (GO:0016272), which is a child term of protein-containing complex. The more specific term is already annotated with both IEA and IDA evidence. The generic ""protein-containing complex"" adds no useful information." human/PFDN2 GO:0032991 protein-containing complex ARBA:ARBA00028902 MARK_AS_OVER_ANNOTATED very general (>200 descendants) 2083 TOO_GENERAL true but uninformative generic Too generic. The more specific term GO:0016272 (prefoldin complex) is already annotated and better describes the actual complex membership. This parent term adds no information. human/PFDN4 GO:0032991 protein-containing complex ARBA:ARBA00028902 MARK_AS_OVER_ANNOTATED very general (>200 descendants) 2083 TOO_GENERAL true but uninformative general "This is an overly general annotation. PFDN4 is part of the prefoldin complex (GO:0016272), which is a child term of protein-containing complex. The more specific term is already annotated with IBA, IEA, and IDA evidence. The generic ""protein-containing complex"" adds no useful information." human/PFDN5 GO:0032991 protein-containing complex ARBA:ARBA00028902 MARK_AS_OVER_ANNOTATED very general (>200 descendants) 2083 TOO_GENERAL true but uninformative general "This is an overly general annotation. PFDN5 is part of the prefoldin complex (GO:0016272), which is a child term of protein-containing complex. The more specific term is already annotated with IBA, IEA, and IDA evidence. The generic ""protein-containing complex"" adds no useful information. Consistent with PFDN1 review decision." human/PFDN6 GO:0032991 protein-containing complex ARBA:ARBA00028902 MARK_AS_OVER_ANNOTATED very general (>200 descendants) 2083 TOO_GENERAL true but uninformative broad While not technically false, this IEA annotation is too broad to be useful for PFDN6 and is superseded by the more specific GO:0016272 prefoldin complex annotations already present. human/PGLS GO:0009051 pentose-phosphate shunt, oxidative branch ARBA:ARBA00028372 ACCEPT leaf (0) 0 human/PHKA1 GO:0004689 phosphorylase kinase activity ARBA:ARBA00045050 MARK_AS_OVER_ANNOTATED leaf (0) 0 UNCLASSIFIED unclassified "Annotating PHKA1 with ""enables phosphorylase kinase activity"" at the protein level over-attributes the holoenzyme's catalytic activity to a regulatory subunit that is itself not a kinase. The activity is better captured as a contribution to the complex (see core_functions contributes_to_molecular_function), not as an activity PHKA1 independently enables." human/PHKA1 GO:0005737 cytoplasm ARBA:ARBA00026971 ACCEPT very general (>200 descendants) 1146 human/PHKA2 GO:0004689 phosphorylase kinase activity ARBA:ARBA00045050 MARK_AS_OVER_ANNOTATED leaf (0) 0 UNCLASSIFIED unclassified The catalytic phosphorylase kinase activity resides in the gamma subunit, not the alpha regulatory subunit. UniProt states that alpha and beta are regulatory subunits while gamma is the catalytic subunit, so an 'enables' assertion of the holoenzyme kinase activity on PHKA2 over-attributes catalysis to a regulatory chain. PHKA2 contributes to this holoenzyme activity as a complex member (captured in core_functions via contributes_to_molecular_function) but does not independently enable it. human/PHKA2 GO:0005737 cytoplasm ARBA:ARBA00026971 ACCEPT very general (>200 descendants) 1146 human/PHYKPL GO:0005759 mitochondrial matrix ARBA:ARBA00028628 ACCEPT specific (1-20) 17 human/PIAS1 GO:0019789 SUMO transferase activity ARBA:ARBA00027358 ACCEPT specific (1-20) 3 human/PICALM GO:0006897 endocytosis ARBA:ARBA00027119 ACCEPT general (21-200) 64 human/PICALM GO:0012505 endomembrane system ARBA:ARBA00028953 ACCEPT very general (>200 descendants) 357 human/PICALM GO:0016020 membrane ARBA:ARBA00028763 ACCEPT very general (>200 descendants) 895 human/PICALM GO:0031982 vesicle ARBA:ARBA00026534 ACCEPT very general (>200 descendants) 290 human/PICALM GO:0048259 regulation of receptor-mediated endocytosis ARBA:ARBA00089722 ACCEPT specific (1-20) 14 human/PICK1 GO:0005737 cytoplasm ARBA:ARBA00026971 KEEP_AS_NON_CORE very general (>200 descendants) 1146 human/PIGW GO:0006505 GPI anchor metabolic process ARBA:ARBA00026294 MARK_AS_OVER_ANNOTATED specific (1-20) 2 TOO_GENERAL true but uninformative parent Not wrong, but a less-informative parent that is fully subsumed by the accepted biosynthetic process annotation. human/PIK3C3 GO:0016773 phosphotransferase activity, alcohol group as acceptor ARBA:ARBA00026265 MODIFY very general (>200 descendants) 311 NEEDS_MORE_SPECIFIC true but uninformative replacement term Human VPS34 has well-defined lipid-substrate specificity, so the specific GO molecular function should replace this high-level transferase term. human/PIK3C3 GO:0036092 phosphatidylinositol-3-phosphate biosynthetic process ARBA:ARBA00090298 ACCEPT specific (1-20) 3 human/PIK3CA GO:0005737 cytoplasm ARBA:ARBA00026971 ACCEPT very general (>200 descendants) 1146 human/PIK3CD GO:0002443 leukocyte mediated immunity ARBA:ARBA00089210 KEEP_AS_NON_CORE general (21-200) 78 human/PIK3CD GO:0005829 cytosol ARBA:ARBA00029243 KEEP_AS_NON_CORE general (21-200) 73 human/PIK3CD GO:0005943 phosphatidylinositol 3-kinase complex, class IA ARBA:ARBA00088348 ACCEPT leaf (0) 0 human/PIK3CD GO:0007166 cell surface receptor signaling pathway ARBA:ARBA00029053 MODIFY very general (>200 descendants) 403 NEEDS_MORE_SPECIFIC true but uninformative replacement term PIK3CD acts downstream of immune receptors such as BCR, TCR, and CD28. Those terms are more informative and better supported than the generic cell-surface receptor signaling parent. human/PIK3CD GO:0010595 positive regulation of endothelial cell migration ARBA:ARBA00092351 KEEP_AS_NON_CORE specific (1-20) 5 human/PIK3CD GO:0010628 positive regulation of gene expression ARBA:ARBA00026655 MARK_AS_OVER_ANNOTATED general (21-200) 198 INDIRECT_EFFECT overreach expression change Gene-expression changes can occur downstream of PI3K/AKT/FOXO signaling, but the evidence supports this as a distal pathway output requiring careful attribution rather than a direct core PIK3CD function. This broad distal term should not be retained as a core annotation. human/PIK3CD GO:0022603 regulation of anatomical structure morphogenesis ARBA:ARBA00026634 MARK_AS_OVER_ANNOTATED very general (>200 descendants) 312 INDIRECT_EFFECT overreach phenotype PIK3CD has specific leukocyte, endothelial, and migration phenotypes, but these broad regulation terms over-generalize downstream effects and obscure the better-supported PI3Kdelta receptor-signaling biology. human/PIK3CD GO:0030155 regulation of cell adhesion ARBA:ARBA00027437 MARK_AS_OVER_ANNOTATED general (21-200) 193 INDIRECT_EFFECT overreach phenotype PIK3CD has specific leukocyte, endothelial, and migration phenotypes, but these broad regulation terms over-generalize downstream effects and obscure the better-supported PI3Kdelta receptor-signaling biology. human/PIK3CD GO:0033031 positive regulation of neutrophil apoptotic process ARBA:ARBA00093050 KEEP_AS_NON_CORE leaf (0) 0 human/PIK3CD GO:0042113 B cell activation ARBA:ARBA00085935 KEEP_AS_NON_CORE general (21-200) 44 human/PIK3CD GO:0051094 positive regulation of developmental process ARBA:ARBA00027577 MARK_AS_OVER_ANNOTATED very general (>200 descendants) 467 INDIRECT_EFFECT overreach phenotype PIK3CD has specific leukocyte, endothelial, and migration phenotypes, but these broad regulation terms over-generalize downstream effects and obscure the better-supported PI3Kdelta receptor-signaling biology. human/PIK3CD GO:0051240 positive regulation of multicellular organismal process ARBA:ARBA00028891 MARK_AS_OVER_ANNOTATED very general (>200 descendants) 565 INDIRECT_EFFECT overreach phenotype PIK3CD has specific leukocyte, endothelial, and migration phenotypes, but these broad regulation terms over-generalize downstream effects and obscure the better-supported PI3Kdelta receptor-signaling biology. human/PIK3CD GO:2000026 regulation of multicellular organismal development ARBA:ARBA00026275 MARK_AS_OVER_ANNOTATED very general (>200 descendants) 464 INDIRECT_EFFECT overreach phenotype PIK3CD has specific leukocyte, endothelial, and migration phenotypes, but these broad regulation terms over-generalize downstream effects and obscure the better-supported PI3Kdelta receptor-signaling biology. human/PIK3R1 GO:0001784 phosphotyrosine residue binding ARBA:ARBA00089668 ACCEPT leaf (0) 0 human/PIK3R1 GO:0005943 phosphatidylinositol 3-kinase complex, class IA ARBA:ARBA00088348 ACCEPT leaf (0) 0 human/PIK3R1 GO:0019207 kinase regulator activity ARBA:ARBA00028075 MODIFY general (21-200) 31 NEEDS_MORE_SPECIFIC true but uninformative replacement term The specific and evidence-backed activity is regulation of the PI3-kinase (p110) catalytic subunit; the generic 'kinase regulator activity' should be replaced by the specific PI3K regulator term. human/PIK3R1 GO:0019903 protein phosphatase binding ARBA:ARBA00087322 KEEP_AS_NON_CORE specific (1-20) 4 human/PIK3R1 GO:0043066 negative regulation of apoptotic process ARBA:ARBA00027746 KEEP_AS_NON_CORE general (21-200) 79 human/PIK3R1 GO:0043491 phosphatidylinositol 3-kinase/protein kinase B signal transduction ARBA:ARBA00085897 ACCEPT leaf (0) 0 human/PIK3R4 GO:0005737 cytoplasm ARBA:ARBA00026971 ACCEPT very general (>200 descendants) 1146 human/PIK3R4 GO:0005856 cytoskeleton ARBA:ARBA00029228 KEEP_AS_NON_CORE very general (>200 descendants) 300 human/PIK3R4 GO:0005929 cilium ARBA:ARBA00028353 KEEP_AS_NON_CORE general (21-200) 115 human/PINK1 GO:0006950 response to stress ARBA:ARBA00026300 KEEP_AS_NON_CORE very general (>200 descendants) 590 human/PINK1 GO:0009966 regulation of signal transduction ARBA:ARBA00027204 KEEP_AS_NON_CORE very general (>200 descendants) 696 human/PINK1 GO:0051049 regulation of transport ARBA:ARBA00027251 KEEP_AS_NON_CORE very general (>200 descendants) 960 human/PINK1 GO:0051246 regulation of protein metabolic process ARBA:ARBA00028884 KEEP_AS_NON_CORE very general (>200 descendants) 442 human/PIP5K1B GO:0051896 regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction ARBA:ARBA00089772 KEEP_AS_NON_CORE specific (1-20) 2 human/PLCG1 GO:0005829 cytosol ARBA:ARBA00029243 ACCEPT general (21-200) 73 human/PLCG1 GO:0019722 calcium-mediated signaling ARBA:ARBA00027115 ACCEPT general (21-200) 22 human/PLCG1 GO:0032587 ruffle membrane ARBA:ARBA00086460 ACCEPT leaf (0) 0 human/PLCG1 GO:0038095 Fc-epsilon receptor signaling pathway ARBA:ARBA00088066 KEEP_AS_NON_CORE specific (1-20) 4 human/PLCG1 GO:0050851 antigen receptor-mediated signaling pathway ARBA:ARBA00091706 ACCEPT specific (1-20) 4 human/PLCG2 GO:0010628 positive regulation of gene expression ARBA:ARBA00026655 KEEP_AS_NON_CORE general (21-200) 198 human/PLCG2 GO:0019722 calcium-mediated signaling ARBA:ARBA00027115 ACCEPT general (21-200) 22 human/PLCG2 GO:0032587 ruffle membrane ARBA:ARBA00086460 ACCEPT leaf (0) 0 human/PLCG2 GO:0038095 Fc-epsilon receptor signaling pathway ARBA:ARBA00088066 ACCEPT specific (1-20) 4 human/PLCG2 GO:0050851 antigen receptor-mediated signaling pathway ARBA:ARBA00091706 ACCEPT specific (1-20) 4 human/PLCG2 GO:1902533 positive regulation of intracellular signal transduction ARBA:ARBA00027124 KEEP_AS_NON_CORE general (21-200) 89 human/PLD3 GO:0005768 endosome ARBA:ARBA00028568 ACCEPT general (21-200) 68 human/PLD4 GO:0005768 endosome ARBA:ARBA00028568 ACCEPT general (21-200) 68 human/PLK1 GO:0000280 nuclear division ARBA:ARBA00028466 ACCEPT general (21-200) 120 human/PLK1 GO:0000922 spindle pole ARBA:ARBA00092938 ACCEPT specific (1-20) 5 human/PLK1 GO:0010564 regulation of cell cycle process ARBA:ARBA00027431 ACCEPT very general (>200 descendants) 338 human/PMM2 GO:0006013 mannose metabolic process ARBA:ARBA00027294 ACCEPT specific (1-20) 4 human/PMPCA GO:0016485 protein processing ARBA:ARBA00028812 ACCEPT general (21-200) 30 human/PMPCB GO:0016485 protein processing ARBA:ARBA00028812 ACCEPT general (21-200) 30 human/PNPLA3 GO:0001676 long-chain fatty acid metabolic process ARBA:ARBA00027692 KEEP_AS_NON_CORE general (21-200) 34 human/PNPLA3 GO:0006654 phosphatidic acid biosynthetic process ARBA:ARBA00087328 MARK_AS_OVER_ANNOTATED leaf (0) 0 INDIRECT_EFFECT overreach downstream This process annotation is downstream of the disputed lysophosphatidic acid acyltransferase activity (see the GO:0003841 entries). Huang et al. found no LPAAT, GPAT or DGAT activity in purified PNPLA3 with CGI-58 as a positive control, and concluded that the enzyme does not promote de novo TAG synthesis. Flagged as over-annotated rather than removed, since the underlying experimental report stands unretracted. human/PNPLA3 GO:0019432 triglyceride biosynthetic process ARBA:ARBA00026657 KEEP_AS_NON_CORE leaf (0) 0 human/PNPLA3 GO:0035727 lysophosphatidic acid binding ARBA:ARBA00092647 MARK_AS_OVER_ANNOTATED leaf (0) 0 UNCLASSIFIED unclassified Lysophosphatidic acid binding was inferred from the LPAAT assays of Kumari et al. and stands or falls with that activity, which Huang et al. could not reproduce. Flagged with the same status as the acyltransferase terms rather than given independent weight. human/PNPLA3 GO:0036042 long-chain fatty acyl-CoA binding ARBA:ARBA00090279 KEEP_AS_NON_CORE leaf (0) 0 human/PPOX GO:0005758 mitochondrial intermembrane space ARBA:ARBA00033592 MARK_AS_OVER_ANNOTATED specific (1-20) 1 TOO_GENERAL true but uninformative more specific "PPOX is anchored to the inner membrane with its active site oriented toward the intermembrane space; UniProt records the location as ""Mitochondrion inner membrane; Peripheral membrane protein; Intermembrane side"". The more specific and accurate component is mitochondrial inner membrane (GO:0005743). Assigning it as an intermembrane-space (matrix-of-the-IMS) protein overstates a free-luminal localisation, so this is an over-annotation relative to the inner-membrane term." human/PPOX GO:0006785 heme B biosynthetic process ARBA:ARBA00093713 ACCEPT leaf (0) 0 human/PPOX GO:0031966 mitochondrial membrane ARBA:ARBA00026364 MARK_AS_OVER_ANNOTATED general (21-200) 36 TOO_GENERAL true but uninformative already annotated PPOX localises specifically to the mitochondrial inner membrane (GO:0005743), which is already annotated. The generic mitochondrial membrane parent is true but redundant and less informative. human/PPP2CA GO:0090443 FAR/SIN/STRIPAK complex ARBA:ARBA00088561 ACCEPT leaf (0) 0 human/PPP2CB GO:0090443 FAR/SIN/STRIPAK complex ARBA:ARBA00088561 ACCEPT leaf (0) 0 human/PPP2R2A GO:0008287 protein serine/threonine phosphatase complex ARBA:ARBA00027535 ACCEPT specific (1-20) 12 human/PPP3CA GO:0033173 calcineurin-NFAT signaling cascade ARBA:ARBA00092841 ACCEPT leaf (0) 0 human/PPP3CB GO:0033173 calcineurin-NFAT signaling cascade ARBA:ARBA00092841 ACCEPT leaf (0) 0 human/PRKN GO:0009896 positive regulation of catabolic process ARBA:ARBA00028093 KEEP_AS_NON_CORE general (21-200) 120 human/PRKN GO:0022603 regulation of anatomical structure morphogenesis ARBA:ARBA00026634 MARK_AS_OVER_ANNOTATED very general (>200 descendants) 312 NO_EVIDENCE overreach No evidence No evidence that Parkin regulates anatomical structure morphogenesis. human/PRKN GO:0050804 modulation of chemical synaptic transmission ARBA:ARBA00029187 KEEP_AS_NON_CORE general (21-200) 116 human/PRKN GO:0098588 bounding membrane of organelle ARBA:ARBA00027281 ACCEPT very general (>200 descendants) 201 human/PRKN GO:1903530 regulation of secretion by cell ARBA:ARBA00027787 KEEP_AS_NON_CORE very general (>200 descendants) 245 human/PRODH GO:0005739 mitochondrion ARBA:ARBA00026962 ACCEPT general (21-200) 70 human/PSAP GO:0008289 lipid binding ARBA:ARBA00027537 ACCEPT general (21-200) 94 human/PSAP GO:0010467 gene expression ARBA:ARBA00028330 MARK_AS_OVER_ANNOTATED very general (>200 descendants) 724 TOO_GENERAL true but uninformative Vague Vague, over-broad ARBA mapping not reflecting a real gene-expression role; the underlying biology is post-translational regulation of progranulin abundance (see the IDA/IMP entries). human/PSAP GO:0042802 identical protein binding ARBA:ARBA00027930 ACCEPT specific (1-20) 1 human/PSEN1 GO:0000776 kinetochore ARBA:ARBA00027576 UNDECIDED specific (1-20) 11 human/PSEN1 GO:0007220 Notch receptor processing ARBA:ARBA00084929 ACCEPT specific (1-20) 2 human/PSEN1 GO:0031965 nuclear membrane ARBA:ARBA00086674 UNDECIDED specific (1-20) 6 human/PSEN2 GO:0000776 kinetochore ARBA:ARBA00027576 KEEP_AS_NON_CORE specific (1-20) 11 human/PSEN2 GO:0006509 membrane protein ectodomain proteolysis ARBA:ARBA00085430 ACCEPT specific (1-20) 1 human/PSEN2 GO:0007220 Notch receptor processing ARBA:ARBA00084929 ACCEPT specific (1-20) 2 human/PSEN2 GO:0031965 nuclear membrane ARBA:ARBA00086674 KEEP_AS_NON_CORE specific (1-20) 6 human/PSMA1 GO:0005829 cytosol ARBA:ARBA00029243 ACCEPT general (21-200) 73 human/PSMB5 GO:0010498 proteasomal protein catabolic process ARBA:ARBA00028386 ACCEPT general (21-200) 21 human/PTCH1 GO:0005119 smoothened binding ARBA:ARBA00085819 KEEP_AS_NON_CORE leaf (0) 0 human/PTCH1 GO:0097108 hedgehog family protein binding ARBA:ARBA00090055 ACCEPT leaf (0) 0 human/PTEN GO:0009966 regulation of signal transduction ARBA:ARBA00027204 MODIFY very general (>200 descendants) 696 NEEDS_MORE_SPECIFIC true but uninformative replacement term Too general. GO:0051898 (negative regulation of PI3K/AKT signaling) is more specific and accurate. human/PTEN GO:0010604 positive regulation of macromolecule metabolic process ARBA:ARBA00026482 REMOVE very general (>200 descendants) 467 WRONG_DIRECTION wrong manual WRONG_DIRECTION This annotation is too vague and potentially misleading. PTEN generally suppresses anabolic metabolism through mTOR inhibition rather than promoting macromolecule metabolism. human/PTEN GO:0010648 negative regulation of cell communication ARBA:ARBA00026586 MODIFY very general (>200 descendants) 305 NEEDS_MORE_SPECIFIC true but uninformative replacement term Too general. GO:0051898 (negative regulation of PI3K/AKT signaling) is the specific pathway PTEN regulates. human/PTEN GO:0019899 enzyme binding ARBA:ARBA00026481 ACCEPT general (21-200) 77 human/PTEN GO:0023057 negative regulation of signaling ARBA:ARBA00026312 MODIFY very general (>200 descendants) 301 NEEDS_MORE_SPECIFIC true but uninformative replacement term Too general. GO:0051898 (negative regulation of PI3K/AKT signaling) is more specific. human/PTEN GO:0045595 regulation of cell differentiation ARBA:ARBA00028479 KEEP_AS_NON_CORE very general (>200 descendants) 697 human/PTEN GO:0051093 negative regulation of developmental process ARBA:ARBA00027583 KEEP_AS_NON_CORE very general (>200 descendants) 504 human/PTEN GO:0051129 negative regulation of cellular component organization ARBA:ARBA00026626 MARK_AS_OVER_ANNOTATED very general (>200 descendants) 285 INDIRECT_EFFECT overreach indirect This is too vague and likely an over-annotation. PTEN's effects on cellular organization are indirect consequences of PI3K/AKT signaling modulation. human/PTEN GO:0051241 negative regulation of multicellular organismal process ARBA:ARBA00033877 MARK_AS_OVER_ANNOTATED very general (>200 descendants) 560 INDIRECT_EFFECT overreach indirect Too vague to be informative. This is an indirect consequence of PTEN's lipid phosphatase activity. human/PTEN GO:0051726 regulation of cell cycle ARBA:ARBA00029144 KEEP_AS_NON_CORE very general (>200 descendants) 377 human/PTEN GO:0042995 cell projection ARBA:ARBA00027299 ACCEPT very general (>200 descendants) 347 human/PTF1A GO:0043565 sequence-specific DNA binding ARBA:ARBA00026779 MODIFY general (21-200) 60 NEEDS_MORE_SPECIFIC true but uninformative replacement term GO:0070888 E-box binding is a more informative description of the PTF1A bHLH DNA-recognition activity. human/PTK2 GO:0001952 regulation of cell-matrix adhesion ARBA:ARBA00091301 ACCEPT specific (1-20) 11 human/PTK2 GO:0007229 integrin-mediated signaling pathway ARBA:ARBA00084939 ACCEPT leaf (0) 0 human/PTK2 GO:0008284 positive regulation of cell population proliferation ARBA:ARBA00027538 KEEP_AS_NON_CORE general (21-200) 85 human/PTK2 GO:0008360 regulation of cell shape ARBA:ARBA00091969 KEEP_AS_NON_CORE general (21-200) 26 human/PTK2 GO:0030154 cell differentiation ARBA:ARBA00027429 MARK_AS_OVER_ANNOTATED very general (>200 descendants) 1345 INDIRECT_EFFECT overreach indirect Too general to be informative; FAK affects differentiation only indirectly through adhesion signalling in specific animal cell types. human/PTK2 GO:0043066 negative regulation of apoptotic process ARBA:ARBA00027746 KEEP_AS_NON_CORE general (21-200) 79 human/PTK2 GO:0045595 regulation of cell differentiation ARBA:ARBA00028479 MARK_AS_OVER_ANNOTATED very general (>200 descendants) 697 INDIRECT_EFFECT overreach indirect Too general; differentiation effects are indirect and cell-type specific (e.g. osteoblasts). human/PTK2 GO:0048010 vascular endothelial growth factor receptor signaling pathway ARBA:ARBA00043614 KEEP_AS_NON_CORE specific (1-20) 5 human/PTK2 GO:0051239 regulation of multicellular organismal process ARBA:ARBA00028859 MARK_AS_OVER_ANNOTATED very general (>200 descendants) 1807 TOO_GENERAL true but uninformative Uninformative Uninformative high-level term; FAK acts at the cell level (adhesion, migration signalling). human/PTPN11 GO:0031295 T cell costimulation ARBA:ARBA00086532 KEEP_AS_NON_CORE specific (1-20) 1 human/PTPN11 GO:0050858 negative regulation of antigen receptor-mediated signaling pathway ARBA:ARBA00091717 KEEP_AS_NON_CORE specific (1-20) 3 human/PTPN11 GO:0051897 positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction ARBA:ARBA00089771 KEEP_AS_NON_CORE leaf (0) 0 human/PTPN11 GO:0060338 regulation of type I interferon-mediated signaling pathway ARBA:ARBA00090811 KEEP_AS_NON_CORE specific (1-20) 2 human/PTPN11 GO:1902564 negative regulation of neutrophil activation ARBA:ARBA00092205 KEEP_AS_NON_CORE leaf (0) 0 human/PTPN6 GO:0031295 T cell costimulation ARBA:ARBA00086532 ACCEPT specific (1-20) 1 human/PTPN6 GO:0051897 positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction ARBA:ARBA00089771 MARK_AS_OVER_ANNOTATED leaf (0) 0 UNCLASSIFIED unclassified The strongest recent synthesis instead supports SHP-1 as a brake that can reduce AKT phosphorylation in receptor-signaling contexts; positive-direction annotations need context-specific support. human/PTPN6 GO:0060338 regulation of type I interferon-mediated signaling pathway ARBA:ARBA00090811 ACCEPT specific (1-20) 2 human/PTPN6 GO:1902564 negative regulation of neutrophil activation ARBA:ARBA00092205 ACCEPT leaf (0) 0 human/PTPRC GO:0098552 side of membrane ARBA:ARBA00027303 KEEP_AS_NON_CORE general (21-200) 61 human/PYCR1 GO:0034599 cellular response to oxidative stress ARBA:ARBA00027632 KEEP_AS_NON_CORE general (21-200) 25 human/PYCR2 GO:0034599 cellular response to oxidative stress ARBA:ARBA00027632 KEEP_AS_NON_CORE general (21-200) 25 human/PYGL GO:0005977 glycogen metabolic process ARBA:ARBA00028497 KEEP_AS_NON_CORE specific (1-20) 3 human/QDPR GO:0042558 pteridine-containing compound metabolic process ARBA:ARBA00027196 KEEP_AS_NON_CORE general (21-200) 37 human/QTGAL GO:0003824 catalytic activity ARBA:ARBA00027533 MODIFY very general (>200 descendants) 6405 NEEDS_MORE_SPECIFIC true but uninformative replacement term "[PMID:37992713 ""Here, we biochemically identified two RNA glycosylases, QTGAL and QTMAN, and successfully reconstituted Q-glycosylation of tRNAs using nucleotide diphosphate sugars.""] [file:human/QTGAL/QTGAL-uniprot.txt ""CC Reaction=queuosine(34) in tRNA(Tyr) + UDP-alpha-D-galactose = O-5''-""]" human/RAB1B GO:0006888 endoplasmic reticulum to Golgi vesicle-mediated transport ARBA:ARBA00027177 ACCEPT specific (1-20) 6 human/RAB1B GO:0007030 Golgi organization ARBA:ARBA00091973 ACCEPT specific (1-20) 15 human/RAB1B GO:1903020 positive regulation of glycoprotein metabolic process ARBA:ARBA00089796 MODIFY specific (1-20) 6 OTHER_TERM different term needed replacement term The IGI comes from PMID:21680502, where the finding is that RAB1A and RAB1B together are needed for herpes simplex virus 1 envelope glycoproteins to move from the ER to the assembly compartment, where they undergo glycosylation. RAB1B does not act on the glycosylation chemistry; it delivers the substrate to the compartment that performs it, so any effect on glycoprotein metabolism is a downstream consequence of anterograde transport. GO:0006888 states this directly and is already annotated to the gene from the same experiment. Redirected there rather than left as a metabolic claim the evidence does not make. human/RAB24 GO:0098588 bounding membrane of organelle ARBA:ARBA00027281 KEEP_AS_NON_CORE very general (>200 descendants) 201 human/RAB7A GO:0098588 bounding membrane of organelle ARBA:ARBA00027281 ACCEPT very general (>200 descendants) 201 human/RAB7B GO:0002682 regulation of immune system process ARBA:ARBA00027003 ACCEPT very general (>200 descendants) 1028 human/RAB7B GO:0031090 organelle membrane ARBA:ARBA00027624 ACCEPT very general (>200 descendants) 333 human/RAB8A GO:0019003 GDP binding ARBA:ARBA00091945 ACCEPT leaf (0) 0 human/RAB9A GO:0031090 organelle membrane ARBA:ARBA00027624 MARK_AS_OVER_ANNOTATED very general (>200 descendants) 333 TOO_GENERAL true but uninformative general This term is too general to be informative. More specific membrane localizations (late endosome, TGN membrane, etc.) are already annotated and provide more useful information about RAB9A function. human/RAB9B GO:0031090 organelle membrane ARBA:ARBA00027624 ACCEPT very general (>200 descendants) 333 human/RABGGTA GO:0005737 cytoplasm ARBA:ARBA00026971 KEEP_AS_NON_CORE very general (>200 descendants) 1146 human/RABGGTB GO:0005737 cytoplasm ARBA:ARBA00026971 KEEP_AS_NON_CORE very general (>200 descendants) 1146 human/RAD18 GO:0005694 chromosome ARBA:ARBA00026361 ACCEPT very general (>200 descendants) 204 human/RAD51B GO:0005694 chromosome ARBA:ARBA00026361 ACCEPT very general (>200 descendants) 204 human/RAD51B GO:0006302 double-strand break repair ARBA:ARBA00027906 ACCEPT general (21-200) 28 human/RAD51D GO:0006302 double-strand break repair ARBA:ARBA00027906 ACCEPT general (21-200) 28 human/RAF1 GO:0043066 negative regulation of apoptotic process ARBA:ARBA00027746 ACCEPT general (21-200) 79 human/RARA GO:0005654 nucleoplasm ARBA:ARBA00026290 KEEP_AS_NON_CORE general (21-200) 65 human/RARA GO:1990837 sequence-specific double-stranded DNA binding ARBA:ARBA00028376 ACCEPT general (21-200) 48 human/RASA1 GO:0005102 signaling receptor binding ARBA:ARBA00027239 ACCEPT very general (>200 descendants) 380 human/RASA1 GO:0005829 cytosol ARBA:ARBA00029243 ACCEPT general (21-200) 73 human/RASA1 GO:0019899 enzyme binding ARBA:ARBA00026481 KEEP_AS_NON_CORE general (21-200) 77 human/RASA1 GO:0048731 system development ARBA:ARBA00027702 MODIFY very general (>200 descendants) 2438 NEEDS_MORE_SPECIFIC true but uninformative replacement term While RASA1 is indeed involved in development, particularly vascular development, this term is too broad. More specific vascular development terms are already annotated (blood vessel morphogenesis, vasculogenesis, angiogenesis). human/RASA3 GO:0006950 response to stress ARBA:ARBA00026300 REMOVE very general (>200 descendants) 590 UNSUPPORTED overreach manual UNSUPPORTED Overly broad annotation without specific evidence for RASA3 involvement in stress response pathways. The ARBA-derived annotation likely reflects general properties of signaling regulators rather than specific RASA3 function. RASA3's core roles are in hematopoiesis, platelet activation, and lymphocyte trafficking - not stress response per se. human/RASAL1 GO:0005829 cytosol ARBA:ARBA00029243 ACCEPT general (21-200) 73 human/RB1 GO:0032502 developmental process ARBA:ARBA00028739 KEEP_AS_NON_CORE very general (>200 descendants) 4075 human/RBPJ GO:0007221 positive regulation of transcription of Notch receptor target ARBA:ARBA00084930 ACCEPT leaf (0) 0 human/RBPJ GO:0048513 animal organ development ARBA:ARBA00029247 KEEP_AS_NON_CORE very general (>200 descendants) 1888 human/RBX1 GO:0004842 ubiquitin-protein transferase activity ARBA:ARBA00026878 ACCEPT specific (1-20) 18 human/RBX1 GO:0006513 protein monoubiquitination ARBA:ARBA00085470 ACCEPT leaf (0) 0 human/RBX1 GO:0031464 Cul4A-RING E3 ubiquitin ligase complex ARBA:ARBA00085920 ACCEPT leaf (0) 0 human/RBX1 GO:0034644 cellular response to UV ARBA:ARBA00026679 KEEP_AS_NON_CORE specific (1-20) 8 human/RBX1 GO:0070936 protein K48-linked ubiquitination ARBA:ARBA00086253 ACCEPT leaf (0) 0 human/RCE1 GO:0004175 endopeptidase activity ARBA:ARBA00028131 MODIFY specific (1-20) 17 OTHER_TERM different term needed replacement term RCE1 is indeed an endopeptidase (cleaves the internal peptide bond releasing the -AAX tripeptide), so this ARBA electronic term is not wrong, but the specific catalytic class is known (glutamic-type). Refine to glutamic-type peptidase activity. human/RCE1 GO:0080120 CAAX-box protein maturation ARBA:ARBA00026983 KEEP_AS_NON_CORE specific (1-20) 1 human/RDH5 GO:0016616 oxidoreductase activity, acting on the CH-OH group of donors, NAD or NADP as acceptor ARBA:ARBA00028442 MARK_AS_OVER_ANNOTATED very general (>200 descendants) 364 TOO_GENERAL true but uninformative general ARBA machine-learning annotation to a very general oxidoreductase parent. True but uninformative relative to the specific 11-cis-retinol dehydrogenase activity. Over-annotation. human/RDH8 GO:0006694 steroid biosynthetic process ARBA:ARBA00028726 REMOVE general (21-200) 29 WRONG_PROCESS wrong manual WRONG_PROCESS Incorrect electronic (IEA/ARBA) inference from the 17beta-HSD-like SDR family. RDH8's demonstrated role is in the retinoid/visual cycle; steroid biosynthesis is not supported. human/RGS20 GO:0003924 GTPase activity ARBA:ARBA00026818 REMOVE specific (1-20) 5 ROLE_CONFUSION wrong manual ROLE_CONFUSION RGS20 does not have GTPase activity. It has GTPase activator activity (GAP activity), meaning it accelerates the GTPase activity of its substrates (Galpha-z, Galpha-i). This is a common over-annotation error where GAP function is confused with GTPase activity. The correct term is GO:0005096 (GTPase activator activity). human/RGS20 GO:0007186 G protein-coupled receptor signaling pathway ARBA:ARBA00029021 ACCEPT very general (>200 descendants) 262 human/RHBDF1 GO:0005737 cytoplasm ARBA:ARBA00026971 KEEP_AS_NON_CORE very general (>200 descendants) 1146 human/RHBDF1 GO:0012505 endomembrane system ARBA:ARBA00028953 KEEP_AS_NON_CORE very general (>200 descendants) 357 human/RIPK2 GO:0001819 positive regulation of cytokine production ARBA:ARBA00028861 KEEP_AS_NON_CORE general (21-200) 86 human/RIPK2 GO:0042742 defense response to bacterium ARBA:ARBA00028625 ACCEPT specific (1-20) 19 human/RIPK2 GO:0070427 nucleotide-binding oligomerization domain containing 1 signaling pathway ARBA:ARBA00085415 ACCEPT leaf (0) 0 human/RIPK2 GO:0140895 cell surface toll-like receptor signaling pathway ARBA:ARBA00087276 KEEP_AS_NON_CORE specific (1-20) 11 human/RNF14 GO:0060828 regulation of canonical Wnt signaling pathway ARBA:ARBA00027468 KEEP_AS_NON_CORE specific (1-20) 2 human/RNF185 GO:0004842 ubiquitin-protein transferase activity ARBA:ARBA00026878 ACCEPT specific (1-20) 18 human/RNF185 GO:0005737 cytoplasm ARBA:ARBA00026971 KEEP_AS_NON_CORE very general (>200 descendants) 1146 human/RNF185 GO:0036503 ERAD pathway ARBA:ARBA00029018 ACCEPT specific (1-20) 3 human/RNF185 GO:1904380 endoplasmic reticulum mannose trimming ARBA:ARBA00089809 REMOVE specific (1-20) 1 ROLE_CONFUSION wrong manual ROLE_CONFUSION RNF185 has no glycosidase/mannosidase activity; mannose trimming is performed by EDEM/ER mannosidases. This electronic inference is biologically incorrect. human/RNF41 GO:0000209 protein polyubiquitination ARBA:ARBA00044436 ACCEPT specific (1-20) 9 human/RNF41 GO:0019899 enzyme binding ARBA:ARBA00026481 KEEP_AS_NON_CORE general (21-200) 77 human/RNF5 GO:0036503 ERAD pathway ARBA:ARBA00029018 ACCEPT specific (1-20) 3 human/RNF5 GO:1904380 endoplasmic reticulum mannose trimming ARBA:ARBA00089809 REMOVE specific (1-20) 1 ROLE_CONFUSION wrong manual ROLE_CONFUSION RNF5 has no glycosidase/mannosidase activity; mannose trimming is performed by EDEM/ER mannosidases, not by the E3 ligase. This electronic inference is biologically incorrect. human/ROR1 GO:0015026 coreceptor activity ARBA:ARBA00026504 ACCEPT leaf (0) 0 human/ROR1 GO:0017147 Wnt-protein binding ARBA:ARBA00085836 ACCEPT leaf (0) 0 human/RORA GO:0010468 regulation of gene expression ARBA:ARBA00028334 MODIFY very general (>200 descendants) 874 NEEDS_MORE_SPECIFIC true but uninformative replacement term RORA directly regulates RNA polymerase II target-gene transcription from cis-regulatory response elements. human/RP2 GO:0005737 cytoplasm ARBA:ARBA00026971 ACCEPT very general (>200 descendants) 1146 human/RPE65 GO:0001523 retinoid metabolic process ARBA:ARBA00028293 ACCEPT specific (1-20) 18 human/RPE65 GO:0120254 olefinic compound metabolic process ARBA:ARBA00033535 MARK_AS_OVER_ANNOTATED general (21-200) 90 TOO_GENERAL true but uninformative Uninformative Uninformatively broad; the specific retinoid/retinal metabolic process and zeaxanthin biosynthesis terms already capture RPE65's substrate metabolism. human/RPGRIP1L GO:0009966 regulation of signal transduction ARBA:ARBA00027204 KEEP_AS_NON_CORE very general (>200 descendants) 696 human/RPN1 GO:0005783 endoplasmic reticulum ARBA:ARBA00028672 KEEP_AS_NON_CORE general (21-200) 100 human/RPS3 GO:0022626 cytosolic ribosome ARBA:ARBA00026577 ACCEPT specific (1-20) 2 human/RRM2B GO:0006281 DNA repair ARBA:ARBA00029008 ACCEPT general (21-200) 74 human/RRM2B GO:0009185 ribonucleoside diphosphate metabolic process ARBA:ARBA00044387 ACCEPT general (21-200) 42 human/RRM2B GO:0009265 2'-deoxyribonucleotide biosynthetic process ARBA:ARBA00090652 ACCEPT general (21-200) 26 human/RRM2B GO:1901992 positive regulation of mitotic cell cycle phase transition ARBA:ARBA00029089 MARK_AS_OVER_ANNOTATED specific (1-20) 8 UNCLASSIFIED unclassified RRM2B does not directly regulate cell-cycle phase transitions; if anything, p53R2 induction promotes a DNA-damage checkpoint arrest (PMID:10716435), not a positive transition. This ARBA-inferred regulatory term over-interprets the enzyme's metabolic role. human/RUNX3 GO:0045893 positive regulation of DNA-templated transcription ARBA:ARBA00029082 ACCEPT general (21-200) 42 human/RUNX3 GO:1990837 sequence-specific double-stranded DNA binding ARBA:ARBA00028376 ACCEPT general (21-200) 48 human/SAMD8 GO:0046513 ceramide biosynthetic process ARBA:ARBA00027419 UNDECIDED specific (1-20) 6 human/SAT1 GO:0006595 polyamine metabolic process ARBA:ARBA00026605 KEEP_AS_NON_CORE specific (1-20) 18 human/SCN1A GO:0001508 action potential ARBA:ARBA00028325 ACCEPT general (21-200) 45 human/SCN9A GO:0001508 action potential ARBA:ARBA00028325 KEEP_AS_NON_CORE general (21-200) 45 human/SCO1 GO:0033617 mitochondrial respiratory chain complex IV assembly ARBA:ARBA00084552 ACCEPT leaf (0) 0 human/SCO2 GO:0033617 mitochondrial respiratory chain complex IV assembly ARBA:ARBA00084552 ACCEPT leaf (0) 0 human/SCP2 GO:0008206 bile acid metabolic process ARBA:ARBA00092298 KEEP_AS_NON_CORE specific (1-20) 3 human/SCP2 GO:0015918 sterol transport ARBA:ARBA00026829 ACCEPT specific (1-20) 19 human/SCP2 GO:0019216 regulation of lipid metabolic process ARBA:ARBA00028119 MARK_AS_OVER_ANNOTATED very general (>200 descendants) 212 TOO_GENERAL true but uninformative broad Regulation of lipid metabolic process (ARBA). SCP2 influences lipid metabolism (e.g. phospholipid synthesis in the ER, steroidogenesis) but this broad regulatory term is not a core function and is only weakly specific. human/SCP2 GO:0019395 fatty acid oxidation ARBA:ARBA00027602 KEEP_AS_NON_CORE specific (1-20) 5 human/SDHAF2 GO:0010719 negative regulation of epithelial to mesenchymal transition ARBA:ARBA00085215 KEEP_AS_NON_CORE specific (1-20) 5 human/SDHAF2 GO:0090090 negative regulation of canonical Wnt signaling pathway ARBA:ARBA00027950 KEEP_AS_NON_CORE leaf (0) 0 human/SEC11A GO:0005787 signal peptidase complex ARBA:ARBA00033963 ACCEPT leaf (0) 0 human/SEC11C GO:0005787 signal peptidase complex ARBA:ARBA00033963 ACCEPT leaf (0) 0 human/SEC63 GO:0006614 SRP-dependent cotranslational protein targeting to membrane ARBA:ARBA00087309 ACCEPT specific (1-20) 3 human/SEC63 GO:0006620 post-translational protein targeting to endoplasmic reticulum membrane ARBA:ARBA00087313 ACCEPT specific (1-20) 2 human/SECISBP2 GO:0001514 selenocysteine incorporation ARBA:ARBA00090133 ACCEPT leaf (0) 0 human/SELENOI GO:0008610 lipid biosynthetic process ARBA:ARBA00027236 MARK_AS_OVER_ANNOTATED very general (>200 descendants) 258 TOO_GENERAL true but uninformative high-level Correct but a high-level generalization. The specific, experimentally supported process is phosphatidylethanolamine biosynthesis (GO:0006646); this generic term adds little and is over-annotated relative to the specific child. human/SFT2D3 GO:0005737 cytoplasm ARBA:ARBA00026971 ACCEPT very general (>200 descendants) 1146 human/SFT2D3 GO:0012505 endomembrane system ARBA:ARBA00028953 ACCEPT very general (>200 descendants) 357 human/SGCA GO:0016010 dystrophin-associated glycoprotein complex ARBA:ARBA00028743 ACCEPT specific (1-20) 4 human/SGPL1 GO:0006629 lipid metabolic process ARBA:ARBA00028591 KEEP_AS_NON_CORE very general (>200 descendants) 608 human/SGPP1 GO:0030149 sphingolipid catabolic process ARBA:ARBA00085904 KEEP_AS_NON_CORE specific (1-20) 11 human/SGPP2 GO:0030149 sphingolipid catabolic process ARBA:ARBA00085904 KEEP_AS_NON_CORE specific (1-20) 11 human/SGTA GO:0016020 membrane ARBA:ARBA00028763 KEEP_AS_NON_CORE very general (>200 descendants) 895 human/SGTA GO:0042802 identical protein binding ARBA:ARBA00027930 ACCEPT specific (1-20) 1 human/SHH GO:0005509 calcium ion binding ARBA:ARBA00043315 KEEP_AS_NON_CORE specific (1-20) 2 human/SHH GO:0007389 pattern specification process ARBA:ARBA00027400 KEEP_AS_NON_CORE very general (>200 descendants) 307 human/SHH GO:0007417 central nervous system development ARBA:ARBA00026561 KEEP_AS_NON_CORE very general (>200 descendants) 464 human/SHH GO:0009888 tissue development ARBA:ARBA00028065 MARK_AS_OVER_ANNOTATED very general (>200 descendants) 1023 INDIRECT_EFFECT overreach consequence The tissue development term is not false, but it is an uninformative umbrella consequence of SHH signaling and is superseded by multiple more specific developmental annotations. human/SHH GO:0030182 neuron differentiation ARBA:ARBA00027575 KEEP_AS_NON_CORE very general (>200 descendants) 323 human/SHH GO:0035295 tube development ARBA:ARBA00027800 MARK_AS_OVER_ANNOTATED very general (>200 descendants) 441 INDIRECT_EFFECT overreach consequence The tube development term is not false, but it is an uninformative umbrella consequence of SHH signaling and is superseded by multiple more specific developmental annotations. human/SHH GO:0042127 regulation of cell population proliferation ARBA:ARBA00027546 KEEP_AS_NON_CORE very general (>200 descendants) 258 human/SHH GO:0045165 cell fate commitment ARBA:ARBA00043601 KEEP_AS_NON_CORE very general (>200 descendants) 245 human/SHH GO:0045880 positive regulation of smoothened signaling pathway ARBA:ARBA00086559 ACCEPT leaf (0) 0 human/SHH GO:0048468 cell development ARBA:ARBA00028665 MARK_AS_OVER_ANNOTATED very general (>200 descendants) 672 INDIRECT_EFFECT overreach consequence The cell development term is not false, but it is an uninformative umbrella consequence of SHH signaling and is superseded by multiple more specific developmental annotations. human/SHH GO:0048513 animal organ development ARBA:ARBA00029247 MARK_AS_OVER_ANNOTATED very general (>200 descendants) 1888 INDIRECT_EFFECT overreach consequence The animal organ development term is not false, but it is an uninformative umbrella consequence of SHH signaling and is superseded by multiple more specific developmental annotations. human/SHH GO:0050793 regulation of developmental process ARBA:ARBA00028689 MARK_AS_OVER_ANNOTATED very general (>200 descendants) 1542 INDIRECT_EFFECT overreach consequence The regulation of developmental process term is not false, but it is an uninformative umbrella consequence of SHH signaling and is superseded by multiple more specific developmental annotations. human/SHMT1 GO:0006544 glycine metabolic process ARBA:ARBA00085449 ACCEPT specific (1-20) 4 human/SHMT1 GO:0006563 L-serine metabolic process ARBA:ARBA00044408 ACCEPT specific (1-20) 2 human/SHMT1 GO:0006730 one-carbon metabolic process ARBA:ARBA00087064 ACCEPT specific (1-20) 1 human/SHMT1 GO:0046653 tetrahydrofolate metabolic process ARBA:ARBA00033901 ACCEPT specific (1-20) 5 human/SHMT2 GO:0006544 glycine metabolic process ARBA:ARBA00085449 ACCEPT specific (1-20) 4 human/SHMT2 GO:0006563 L-serine metabolic process ARBA:ARBA00044408 ACCEPT specific (1-20) 2 human/SHMT2 GO:0006730 one-carbon metabolic process ARBA:ARBA00087064 ACCEPT specific (1-20) 1 human/SHMT2 GO:0046653 tetrahydrofolate metabolic process ARBA:ARBA00033901 KEEP_AS_NON_CORE specific (1-20) 5 human/SHMT2 GO:0051289 protein homotetramerization ARBA:ARBA00089320 KEEP_AS_NON_CORE leaf (0) 0 human/SHMT2 GO:0120567 hydroxytrimethyllysine aldolase activity ARBA:ARBA00095355 KEEP_AS_NON_CORE leaf (0) 0 human/SIAH1 GO:0060070 canonical Wnt signaling pathway ARBA:ARBA00026624 KEEP_AS_NON_CORE specific (1-20) 5 human/SIAH1 GO:1990000 amyloid fibril formation ARBA:ARBA00087261 MARK_AS_OVER_ANNOTATED leaf (0) 0 SUBSTRATE_OR_CARGO wrong is the substrate SIAH1 monoubiquitylates alpha-synuclein and ubiquitinates synphilin-1 and influences inclusion formation, but amyloid fibril formation is the substrate's property; assigning it as a SIAH1 process is an over-annotation. human/SIAH1 GO:2001233 regulation of apoptotic signaling pathway ARBA:ARBA00027033 KEEP_AS_NON_CORE general (21-200) 57 human/SIRT1 GO:0032436 positive regulation of proteasomal ubiquitin-dependent protein catabolic process ARBA:ARBA00084330 KEEP_AS_NON_CORE specific (1-20) 2 human/SIRT1 GO:0043161 proteasome-mediated ubiquitin-dependent protein catabolic process ARBA:ARBA00026940 KEEP_AS_NON_CORE specific (1-20) 13 human/SIRT1 GO:0046890 regulation of lipid biosynthetic process ARBA:ARBA00028228 KEEP_AS_NON_CORE general (21-200) 139 human/SIRT1 GO:0046970 histone H4K16 deacetylase activity, NAD-dependent ARBA:ARBA00084753 ACCEPT leaf (0) 0 human/SIRT1 GO:0050793 regulation of developmental process ARBA:ARBA00028689 KEEP_AS_NON_CORE very general (>200 descendants) 1542 human/SIRT1 GO:0051239 regulation of multicellular organismal process ARBA:ARBA00028859 KEEP_AS_NON_CORE very general (>200 descendants) 1807 human/SIRT1 GO:0062013 positive regulation of small molecule metabolic process ARBA:ARBA00089138 KEEP_AS_NON_CORE general (21-200) 110 human/SIRT1 GO:0071456 cellular response to hypoxia ARBA:ARBA00092776 KEEP_AS_NON_CORE specific (1-20) 2 human/SIRT2 GO:0043161 proteasome-mediated ubiquitin-dependent protein catabolic process ARBA:ARBA00026940 KEEP_AS_NON_CORE specific (1-20) 13 human/SIRT2 GO:0046890 regulation of lipid biosynthetic process ARBA:ARBA00028228 KEEP_AS_NON_CORE general (21-200) 139 human/SIRT2 GO:0046970 histone H4K16 deacetylase activity, NAD-dependent ARBA:ARBA00084753 ACCEPT leaf (0) 0 human/SIRT2 GO:0051093 negative regulation of developmental process ARBA:ARBA00027583 MARK_AS_OVER_ANNOTATED very general (>200 descendants) 504 TOO_GENERAL true but uninformative broad Too broad and vague. More specific terms should be used for SIRT2's roles in specific developmental contexts. human/SIRT2 GO:0051239 regulation of multicellular organismal process ARBA:ARBA00028859 MARK_AS_OVER_ANNOTATED very general (>200 descendants) 1807 TOO_GENERAL true but uninformative general Too general to be informative. More specific process terms are appropriate. human/SIRT2 GO:0062013 positive regulation of small molecule metabolic process ARBA:ARBA00089138 MARK_AS_OVER_ANNOTATED general (21-200) 110 TOO_GENERAL true but uninformative general Too general. More specific metabolic process terms are more informative. human/SIRT2 GO:0071456 cellular response to hypoxia ARBA:ARBA00092776 KEEP_AS_NON_CORE specific (1-20) 2 human/SIRT5 GO:0016747 acyltransferase activity, transferring groups other than amino-acyl groups ARBA:ARBA00027717 UNDECIDED very general (>200 descendants) 345 human/SIX3 GO:0007601 visual perception ARBA:ARBA00086021 REMOVE specific (1-20) 1 TERM_MISREAD wrong manual TERM_MISREAD SIX3 is a developmental TF patterning the eye field, lens and neuroretina; it does not participate in the sensory process of visual perception. Machine-learned over-propagation. human/SIX6 GO:0007601 visual perception ARBA:ARBA00086021 REMOVE specific (1-20) 1 TERM_MISREAD wrong manual TERM_MISREAD SIX6 is a developmental TF for retinal/optic and pituitary progenitors; it does not participate in the sensory process of visual perception. Machine-learned over-propagation. human/SKP2 GO:0000082 G1/S transition of mitotic cell cycle ARBA:ARBA00028571 ACCEPT leaf (0) 0 human/SKP2 GO:0006511 ubiquitin-dependent protein catabolic process ARBA:ARBA00026385 ACCEPT specific (1-20) 18 human/SLC22A5 GO:0015199 amino-acid betaine transmembrane transporter activity ARBA:ARBA00088543 KEEP_AS_NON_CORE specific (1-20) 3 human/SLC22A5 GO:0015837 amine transport ARBA:ARBA00096986 KEEP_AS_NON_CORE specific (1-20) 16 human/SLC22A5 GO:0030165 PDZ domain binding ARBA:ARBA00085880 KEEP_AS_NON_CORE leaf (0) 0 human/SLC25A10 GO:0005310 dicarboxylic acid transmembrane transporter activity ARBA:ARBA00033522 KEEP_AS_NON_CORE general (21-200) 50 human/SLC25A11 GO:0015139 alpha-ketoglutarate transmembrane transporter activity ARBA:ARBA00088438 KEEP_AS_NON_CORE specific (1-20) 3 human/SLC25A12 GO:0000514 3-sulfino-L-alanine: proton, glutamate antiporter activity ARBA:ARBA00091656 ACCEPT leaf (0) 0 human/SLC25A12 GO:0000515 aspartate:glutamate, proton antiporter activity ARBA:ARBA00091659 ACCEPT leaf (0) 0 human/SLC25A12 GO:0043490 malate-aspartate shuttle ARBA:ARBA00043538 ACCEPT leaf (0) 0 human/SLC25A12 GO:0051592 response to calcium ion ARBA:ARBA00088699 ACCEPT specific (1-20) 3 human/SLC25A13 GO:0000514 3-sulfino-L-alanine: proton, glutamate antiporter activity ARBA:ARBA00091656 KEEP_AS_NON_CORE leaf (0) 0 human/SLC25A13 GO:0000515 aspartate:glutamate, proton antiporter activity ARBA:ARBA00091659 ACCEPT leaf (0) 0 human/SLC25A13 GO:0043490 malate-aspartate shuttle ARBA:ARBA00043538 ACCEPT leaf (0) 0 human/SLC25A13 GO:0051592 response to calcium ion ARBA:ARBA00088699 KEEP_AS_NON_CORE specific (1-20) 3 human/SLC25A15 GO:0000064 L-ornithine transmembrane transporter activity ARBA:ARBA00090257 ACCEPT specific (1-20) 2 human/SLC25A15 GO:0015297 antiporter activity ARBA:ARBA00028010 ACCEPT general (21-200) 86 human/SLC25A19 GO:0005739 mitochondrion ARBA:ARBA00026962 ACCEPT general (21-200) 70 human/SLC25A19 GO:0015932 nucleobase-containing compound transmembrane transporter activity ARBA:ARBA00026791 REMOVE general (21-200) 64 WRONG_ACTIVITY wrong manual WRONG_ACTIVITY "Electronic (ARBA) molecular-function prediction of nucleobase-containing compound transmembrane transporter activity. This is a wrong-substrate over-prediction rooted in the obsolete ""deoxynucleotide carrier"" view of SLC25A19. The physiological substrate is thiamine pyrophosphate, not nucleotides, and GOA carries explicit NOT annotations against deoxynucleotide transporter activity. Remove this electronic annotation." human/SLC25A19 GO:0042723 thiamine-containing compound metabolic process ARBA:ARBA00028583 KEEP_AS_NON_CORE specific (1-20) 12 human/SLC25A19 GO:0090422 thiamine pyrophosphate transmembrane transporter activity ARBA:ARBA00043643 ACCEPT leaf (0) 0 human/SLC25A24 GO:0140987 ATP:phosphate antiporter activity ARBA:ARBA00087021 ACCEPT leaf (0) 0 human/SLC25A26 GO:0005739 mitochondrion ARBA:ARBA00026962 KEEP_AS_NON_CORE general (21-200) 70 human/SLC25A3 GO:0005739 mitochondrion ARBA:ARBA00026962 KEEP_AS_NON_CORE general (21-200) 70 human/SLC25A3 GO:0016020 membrane ARBA:ARBA00028763 MARK_AS_OVER_ANNOTATED very general (>200 descendants) 895 TOO_GENERAL true but uninformative Root "Root-level ""membrane"" is uninformative; superseded by the specific mitochondrial inner-membrane annotation." human/SLC25A32 GO:0015215 nucleotide transmembrane transporter activity ARBA:ARBA00027812 MARK_AS_OVER_ANNOTATED general (21-200) 24 TOO_GENERAL true but uninformative general Over-generalized ARBA-derived molecular-function annotation. The specific and well-supported activity is FAD transmembrane transporter activity (GO:0015230); this generic nucleotide-carrier term is an uninformative parent. If retained it should be replaced by the specific FAD term. human/SLC25A36 GO:0006862 nucleotide transport ARBA:ARBA00027032 MARK_AS_OVER_ANNOTATED general (21-200) 58 TOO_GENERAL true but uninformative general Over-generalized ARBA-derived annotation. SLC25A36 does mediate nucleotide transport, but this generic term is a distant, uninformative parent of the specific and experimentally supported pyrimidine nucleotide import into mitochondrion (GO:1990519). Over-annotation. human/SLC25A4 GO:0005739 mitochondrion ARBA:ARBA00026962 KEEP_AS_NON_CORE general (21-200) 70 human/SLC25A42 GO:0005739 mitochondrion ARBA:ARBA00026962 KEEP_AS_NON_CORE general (21-200) 70 human/SLC25A42 GO:0015605 organophosphate ester transmembrane transporter activity ARBA:ARBA00029098 KEEP_AS_NON_CORE general (21-200) 61 human/SLC25A42 GO:0015932 nucleobase-containing compound transmembrane transporter activity ARBA:ARBA00026791 KEEP_AS_NON_CORE general (21-200) 64 human/SLC25A46 GO:0007005 mitochondrion organization ARBA:ARBA00026723 KEEP_AS_NON_CORE general (21-200) 37 human/SLC25A5 GO:0005739 mitochondrion ARBA:ARBA00026962 ACCEPT general (21-200) 70 human/SLC25A6 GO:0005739 mitochondrion ARBA:ARBA00026962 KEEP_AS_NON_CORE general (21-200) 70 human/SLC27A5 GO:0006631 fatty acid metabolic process ARBA:ARBA00028669 MARK_AS_OVER_ANNOTATED general (21-200) 94 TOO_GENERAL true but uninformative Generic Generic parent term; the more specific long-chain fatty acid metabolic process (GO:0001676) and bile acid metabolic process (GO:0008206) annotations capture the function more precisely. human/SLC27A5 GO:0015245 fatty acid transmembrane transporter activity ARBA:ARBA00088207 MARK_AS_OVER_ANNOTATED specific (1-20) 8 TOO_GENERAL true but uninformative Redundant Redundant generic transporter term; the specific LCFA transporter term is already present, and this activity is non-core relative to the acyl-CoA ligase function. human/SLC27A5 GO:0015909 long-chain fatty acid transport ARBA:ARBA00088749 KEEP_AS_NON_CORE specific (1-20) 10 human/SLC35A1 GO:0015748 organophosphate ester transport ARBA:ARBA00028511 MARK_AS_OVER_ANNOTATED general (21-200) 166 TOO_GENERAL true but uninformative general Over-general machine-learning (ARBA) annotation; not wrong in the broadest sense but uninformative relative to the specific CMP-sialic acid transport function. human/SLC35A1 GO:0015931 nucleobase-containing compound transport ARBA:ARBA00026790 MARK_AS_OVER_ANNOTATED general (21-200) 165 TOO_GENERAL true but uninformative general Over-general automated annotation; the specific CMP-N-acetylneuraminate transport term is the appropriate level. human/SLC3A1 GO:0016020 membrane ARBA:ARBA00028763 ACCEPT very general (>200 descendants) 895 human/SLC3A2 GO:0015823 phenylalanine transport ARBA:ARBA00088963 ACCEPT specific (1-20) 2 human/SLC3A2 GO:0015827 tryptophan transport ARBA:ARBA00088957 ACCEPT specific (1-20) 5 human/SLC3A2 GO:0016020 membrane ARBA:ARBA00028763 ACCEPT very general (>200 descendants) 895 human/SLC3A2 GO:0046982 protein heterodimerization activity ARBA:ARBA00027597 ACCEPT leaf (0) 0 human/SLC40A1 GO:0055085 transmembrane transport ARBA:ARBA00027679 ACCEPT very general (>200 descendants) 1467 human/SLC45A4 GO:0015203 polyamine transmembrane transporter activity ARBA:ARBA00027784 ACCEPT specific (1-20) 8 human/SLC45A4 GO:0019233 sensory perception of pain ARBA:ARBA00095233 ACCEPT specific (1-20) 5 human/SLC7A11 GO:0015813 L-glutamate transmembrane transport ARBA:ARBA00043350 ACCEPT specific (1-20) 11 human/SLC7A11 GO:0043067 regulation of programmed cell death ARBA:ARBA00027742 MODIFY very general (>200 descendants) 257 NEEDS_MORE_SPECIFIC true but uninformative replacement term Too general. SLC7A11 specifically negatively regulates ferroptosis (GO:0110076), a specific form of regulated cell death, through its role in GSH synthesis. human/SLX4 GO:0032206 positive regulation of telomere maintenance ARBA:ARBA00047239 KEEP_AS_NON_CORE specific (1-20) 11 human/SMAD3 GO:0032502 developmental process ARBA:ARBA00028739 MARK_AS_OVER_ANNOTATED very general (>200 descendants) 4075 TOO_GENERAL true but uninformative broad Excessively broad. While TGF-beta/SMAD3 signaling contributes to development, GO:0032502 is too general to be informative. More specific developmental processes are annotated elsewhere. human/SMAD3 GO:0071363 cellular response to growth factor stimulus ARBA:ARBA00027976 ACCEPT general (21-200) 50 human/SMAD3 GO:0141091 transforming growth factor beta receptor superfamily signaling pathway ARBA:ARBA00043534 ACCEPT specific (1-20) 10 human/SMO GO:0009888 tissue development ARBA:ARBA00028065 MARK_AS_OVER_ANNOTATED very general (>200 descendants) 1023 INDIRECT_EFFECT overreach downstream Marked as over-annotated. The source (GO_REF:0000117; electronic inference) supports pathway perturbation or a downstream phenotype, whereas SMO directly performs receptor/transducer, sterol-binding, Gi-coupling, and PKA-inhibitory functions. human/SMO GO:0120025 plasma membrane bounded cell projection ARBA:ARBA00028036 MODIFY very general (>200 descendants) 303 NEEDS_MORE_SPECIFIC true but uninformative replacement term Modify to the more informative cilium (GO:0005929). The replacement preserves the source inference (GO_REF:0000117) while matching the experimentally established specificity of SMO. human/SMOX GO:0046592 polyamine oxidase activity ARBA:ARBA00034971 MODIFY specific (1-20) 5 NEEDS_MORE_SPECIFIC true but uninformative replacement term A more specific, experimentally supported term (GO:0052901) exists and is the enzyme's characterized activity. human/SMPD1 GO:0001778 plasma membrane repair ARBA:ARBA00033547 KEEP_AS_NON_CORE leaf (0) 0 human/SMS GO:0005829 cytosol ARBA:ARBA00029243 ACCEPT general (21-200) 73 human/SMS GO:0006595 polyamine metabolic process ARBA:ARBA00026605 KEEP_AS_NON_CORE specific (1-20) 18 human/SNRPGP15 GO:0030532 small nuclear ribonucleoprotein complex ARBA:ARBA00033820 REMOVE specific (1-20) 20 OBSOLETE_OR_PSEUDOGENE wrong manual OBSOLETE_OR_PSEUDOGENE SNRPGP15 is an HGNC pseudogene locus (Ensembl biotype processed_pseudogene) and A8MWD9 is PE5 with a UniProt pseudogene CAUTION. The GRCh38 locus and the UniProt-cited clone AC012318 both carry TGA at codon 75 (Arg75 in SNRPG), so the 76-residue UniProt sequence is not what the genome encodes. All 16 mass-spectrometry peptides mapped to A8MWD9 are exact SNRPG substrings, and the discriminating tryptic peptides (NIGMVEIR, GFDPFMNLVIDECVEMATSGQQK) have never been observed although SNRPG peptides are seen tens of thousands of times. No literature or experimental data exist for this locus. Automatic transfer from domain signatures adds no locus-specific evidence. Remove. human/SOCS1 GO:0032502 developmental process ARBA:ARBA00028739 MARK_AS_OVER_ANNOTATED very general (>200 descendants) 4075 TOO_GENERAL true but uninformative Root Root-level/very general term with no specific support; over-annotation. human/SORL1 GO:0005041 low-density lipoprotein particle receptor activity ARBA:ARBA00043573 ACCEPT leaf (0) 0 human/SOS1 GO:0005829 cytosol ARBA:ARBA00029243 ACCEPT general (21-200) 73 human/SOS2 GO:0005829 cytosol ARBA:ARBA00029243 ACCEPT general (21-200) 73 human/SOX9 GO:0045893 positive regulation of DNA-templated transcription ARBA:ARBA00029082 ACCEPT general (21-200) 42 human/SOX9 GO:1990837 sequence-specific double-stranded DNA binding ARBA:ARBA00028376 ACCEPT general (21-200) 48 human/SPCS3 GO:0005783 endoplasmic reticulum ARBA:ARBA00028672 ACCEPT general (21-200) 100 human/SPG21 GO:0007166 cell surface receptor signaling pathway ARBA:ARBA00029053 MARK_AS_OVER_ANNOTATED very general (>200 descendants) 403 TOO_GENERAL true but uninformative broad Maspardin is not a component of a cell-surface receptor pathway. Its only tie to receptor signalling is a single unreplicated two-hybrid interaction with the CD4 cytoplasmic tail, and the process term derived from it is both unsupported and too broad to be informative. An electronic generalisation of a narrow, dated observation. human/SPHK1 GO:0019216 regulation of lipid metabolic process ARBA:ARBA00028119 MARK_AS_OVER_ANNOTATED very general (>200 descendants) 212 TOO_GENERAL true but uninformative general ARBA electronic annotation. Very general; SPHK1 is directly a sphingolipid metabolic enzyme, so the specific metabolic-process terms are preferable. human/SPHK1 GO:0031410 cytoplasmic vesicle ARBA:ARBA00027190 KEEP_AS_NON_CORE very general (>200 descendants) 274 human/SPHK1 GO:0038036 sphingosine-1-phosphate receptor activity ARBA:ARBA00088009 REMOVE leaf (0) 0 ROLE_CONFUSION wrong manual ROLE_CONFUSION Incorrect. SPHK1 is the intracellular kinase that produces S1P, not a cell surface S1P receptor (the S1P receptors are S1PR1-5). This ARBA electronic annotation is a wrong-branch molecular-function error and should be removed. human/SPHK1 GO:0046512 sphingosine biosynthetic process ARBA:ARBA00027422 MODIFY leaf (0) 0 TOO_SPECIFIC overreach replacement term As with the IBA copy, this term describes synthesis of the sphingosine base, whereas SPHK1 consumes sphingosine to produce S1P. Better replaced by sphingosine metabolic process. human/SPHK1 GO:0051049 regulation of transport ARBA:ARBA00027251 MARK_AS_OVER_ANNOTATED very general (>200 descendants) 960 TOO_GENERAL true but uninformative general Very general ARBA annotation. SPHK1's trafficking roles are better captured by regulation of endocytosis/endosomal fusion terms. human/SPHK1 GO:0051239 regulation of multicellular organismal process ARBA:ARBA00028859 MARK_AS_OVER_ANNOTATED very general (>200 descendants) 1807 TOO_GENERAL true but uninformative general Extremely general ARBA grouping term with little annotation value. human/SPHK1 GO:0071363 cellular response to growth factor stimulus ARBA:ARBA00027976 KEEP_AS_NON_CORE general (21-200) 50 human/SPHK2 GO:0019216 regulation of lipid metabolic process ARBA:ARBA00028119 MARK_AS_OVER_ANNOTATED very general (>200 descendants) 212 TOO_GENERAL true but uninformative broad ARBA electronic annotation to a broad regulatory term. SPHK2 participates in lipid (sphingolipid) metabolism; this generic 'regulation of lipid metabolic process' is an imprecise over-annotation relative to the specific sphingolipid terms. human/SPHK2 GO:0038036 sphingosine-1-phosphate receptor activity ARBA:ARBA00088009 REMOVE leaf (0) 0 ROLE_CONFUSION wrong manual ROLE_CONFUSION Incorrect molecular function. GO:0038036 denotes a G-protein-coupled receptor that binds S1P and transduces a signal across the membrane. SPHK2 is the kinase that PRODUCES S1P, not the receptor. This is an erroneous ARBA electronic annotation. human/SPHK2 GO:0042981 regulation of apoptotic process ARBA:ARBA00027086 MARK_AS_OVER_ANNOTATED very general (>200 descendants) 218 TOO_GENERAL true but uninformative Broad Broad ARBA electronic term. SPHK2 modulates apoptosis (usually positively); the more specific 'positive regulation of apoptotic process' captures this better. human/SPHK2 GO:0046512 sphingosine biosynthetic process ARBA:ARBA00027422 KEEP_AS_NON_CORE leaf (0) 0 human/SPHK2 GO:0051049 regulation of transport ARBA:ARBA00027251 MARK_AS_OVER_ANNOTATED very general (>200 descendants) 960 TOO_GENERAL true but uninformative broad Very broad ARBA electronic annotation with no specific experimental support for SPHK2 regulating transport. Over-annotation. human/SPNS1 GO:0006869 lipid transport ARBA:ARBA00027046 MODIFY general (21-200) 174 NEEDS_MORE_SPECIFIC true but uninformative replacement term The broad lipid transport term should be replaced by more informative lysophospholipid transport and phospholipid efflux terms. human/SPOCK1 GO:0008191 metalloendopeptidase inhibitor activity ARBA:ARBA00092724 ACCEPT leaf (0) 0 human/SPOCK2 GO:0008191 metalloendopeptidase inhibitor activity ARBA:ARBA00092724 MODIFY leaf (0) 0 TOO_SPECIFIC overreach replacement term Same issue as the IBA annotation for GO:0008191. The computational prediction is reasonable based on domain content but contradicts experimental evidence showing SPOCK2's unique counter-inhibitory function. Should be replaced with regulatory terms. human/SPOCK3 GO:0008191 metalloendopeptidase inhibitor activity ARBA:ARBA00092724 ACCEPT leaf (0) 0 human/SPTLC2 GO:0017059 serine palmitoyltransferase complex ARBA:ARBA00086250 ACCEPT leaf (0) 0 human/SPTLC2 GO:0046512 sphingosine biosynthetic process ARBA:ARBA00027422 ACCEPT leaf (0) 0 human/SQSTM1 GO:0016234 inclusion body ARBA:ARBA00086956 KEEP_AS_NON_CORE specific (1-20) 20 human/SQSTM1 GO:0031399 regulation of protein modification process ARBA:ARBA00028315 KEEP_AS_NON_CORE general (21-200) 169 human/SRC GO:0002862 negative regulation of inflammatory response to antigenic stimulus ARBA:ARBA00090107 KEEP_AS_NON_CORE specific (1-20) 10 human/SRC GO:0005829 cytosol ARBA:ARBA00029243 ACCEPT general (21-200) 73 human/SRC GO:0031295 T cell costimulation ARBA:ARBA00086532 KEEP_AS_NON_CORE specific (1-20) 1 human/SRC GO:0034614 cellular response to reactive oxygen species ARBA:ARBA00043492 KEEP_AS_NON_CORE specific (1-20) 13 human/SRC GO:0038096 Fc-gamma receptor signaling pathway involved in phagocytosis ARBA:ARBA00088071 KEEP_AS_NON_CORE leaf (0) 0 human/SRC GO:0043114 regulation of vascular permeability ARBA:ARBA00084394 KEEP_AS_NON_CORE specific (1-20) 13 human/SRC GO:0045937 positive regulation of phosphate metabolic process ARBA:ARBA00028182 MARK_AS_OVER_ANNOTATED general (21-200) 33 TOO_GENERAL true but uninformative vague ARBA prediction; positive regulation of phosphate metabolic process is too vague to describe SRC function and adds nothing beyond its kinase activity. human/SRC GO:0048013 ephrin receptor signaling pathway ARBA:ARBA00028551 KEEP_AS_NON_CORE specific (1-20) 3 human/SRC GO:0050900 leukocyte migration ARBA:ARBA00091273 KEEP_AS_NON_CORE general (21-200) 63 human/SRC GO:0051057 positive regulation of small GTPase mediated signal transduction ARBA:ARBA00088034 KEEP_AS_NON_CORE specific (1-20) 5 human/SRM GO:0006596 polyamine biosynthetic process ARBA:ARBA00026615 KEEP_AS_NON_CORE specific (1-20) 6 human/SRP68 GO:0005829 cytosol ARBA:ARBA00029243 ACCEPT general (21-200) 73 human/SRP72 GO:0005829 cytosol ARBA:ARBA00029243 ACCEPT general (21-200) 73 human/SRP9 GO:0005829 cytosol ARBA:ARBA00029243 ACCEPT general (21-200) 73 human/STAR GO:0015918 sterol transport ARBA:ARBA00026829 MODIFY specific (1-20) 19 NEEDS_MORE_SPECIFIC true but uninformative replacement term Accurate but general; StAR's cargo is specifically cholesterol, so the more precise intracellular cholesterol transport / cholesterol transport terms better describe the function. human/STAR GO:0042446 hormone biosynthetic process ARBA:ARBA00028013 MODIFY general (21-200) 21 OTHER_TERM different term needed replacement term The hormones StAR contributes to are specifically steroid hormones; the more precise steroid hormone biosynthetic process term (also annotated) better captures this. human/STAR GO:0120178 steroid hormone biosynthetic process ARBA:ARBA00027332 ACCEPT specific (1-20) 9 human/STAT1 GO:0000981 DNA-binding transcription factor activity, RNA polymerase II-specific ARBA:ARBA00029016 ACCEPT specific (1-20) 8 human/STAT1 GO:0005654 nucleoplasm ARBA:ARBA00026290 ACCEPT general (21-200) 65 human/STAT1 GO:0042981 regulation of apoptotic process ARBA:ARBA00027086 KEEP_AS_NON_CORE very general (>200 descendants) 218 human/STAT1 GO:0051093 negative regulation of developmental process ARBA:ARBA00027583 KEEP_AS_NON_CORE very general (>200 descendants) 504 human/STAT1 GO:0060333 type II interferon-mediated signaling pathway ARBA:ARBA00090813 ACCEPT specific (1-20) 1 human/STAT1 GO:0060337 type I interferon-mediated signaling pathway ARBA:ARBA00033815 ACCEPT specific (1-20) 1 human/STAT1 GO:0005829 cytosol ARBA:ARBA00029243 ACCEPT general (21-200) 73 human/STAT1 GO:0090575 RNA polymerase II transcription regulator complex ARBA:ARBA00028248 ACCEPT general (21-200) 44 human/STAT2 GO:0060337 type I interferon-mediated signaling pathway ARBA:ARBA00033815 ACCEPT specific (1-20) 1 human/STAT2 GO:0060339 negative regulation of type I interferon-mediated signaling pathway ARBA:ARBA00090810 ACCEPT leaf (0) 0 human/STAT3 GO:0001817 regulation of cytokine production ARBA:ARBA00028860 KEEP_AS_NON_CORE very general (>200 descendants) 259 human/STAT3 GO:0006955 immune response ARBA:ARBA00026313 KEEP_AS_NON_CORE very general (>200 descendants) 207 human/STAT3 GO:0019221 cytokine-mediated signaling pathway ARBA:ARBA00028236 ACCEPT general (21-200) 120 human/STAT3 GO:0045893 positive regulation of DNA-templated transcription ARBA:ARBA00029082 ACCEPT general (21-200) 42 human/STAT3 GO:0051240 positive regulation of multicellular organismal process ARBA:ARBA00028891 KEEP_AS_NON_CORE very general (>200 descendants) 565 human/STAT3 GO:0090575 RNA polymerase II transcription regulator complex ARBA:ARBA00028248 ACCEPT general (21-200) 44 human/STAT4 GO:0005829 cytosol ARBA:ARBA00029243 ACCEPT general (21-200) 73 human/STAT4 GO:0006955 immune response ARBA:ARBA00026313 ACCEPT very general (>200 descendants) 207 human/STAT4 GO:0019221 cytokine-mediated signaling pathway ARBA:ARBA00028236 ACCEPT general (21-200) 120 human/STAT4 GO:0090575 RNA polymerase II transcription regulator complex ARBA:ARBA00028248 ACCEPT general (21-200) 44 human/STAT5A GO:0019221 cytokine-mediated signaling pathway ARBA:ARBA00028236 ACCEPT general (21-200) 120 human/STAT5A GO:1903706 regulation of hemopoiesis ARBA:ARBA00029137 KEEP_AS_NON_CORE general (21-200) 138 human/STAT5B GO:0019221 cytokine-mediated signaling pathway ARBA:ARBA00028236 ACCEPT general (21-200) 120 human/STAT5B GO:1903706 regulation of hemopoiesis ARBA:ARBA00029137 ACCEPT general (21-200) 138 human/STK3 GO:0006606 protein import into nucleus ARBA:ARBA00028627 MARK_AS_OVER_ANNOTATED specific (1-20) 2 UNCLASSIFIED unclassified STK3 does not carry out nuclear import. The best-characterized output of STK3 is the opposite, retention of YAP/TAZ in the cytoplasm through LATS1/2. A role in FOXO nuclear translocation was described for MST1 in the cited FOXO study and, at most, would be regulation of import, not import itself. human/STK3 GO:0006915 apoptotic process ARBA:ARBA00027755 KEEP_AS_NON_CORE general (21-200) 115 human/STK3 GO:0035332 positive regulation of hippo signaling ARBA:ARBA00091325 MODIFY leaf (0) 0 TOO_SPECIFIC overreach replacement term As above: STK3 is the hippo kinase itself and is better annotated to hippo signaling. human/STK3 GO:0043539 protein serine/threonine kinase activator activity ARBA:ARBA00085523 MARK_AS_OVER_ANNOTATED specific (1-20) 2 TOO_GENERAL true but uninformative already captured STK3 activates LATS1/2 and NDR1 by phosphorylating them (and MOB1), a catalytic mechanism already captured by protein serine/threonine kinase activity. The activator activity term (GO:0043539) is for molecular function regulators that act by binding, e.g. MOB1 for LATS/NDR. Using both terms double-counts the same activity. human/STK3 GO:0045926 negative regulation of growth ARBA:ARBA00028151 KEEP_AS_NON_CORE general (21-200) 47 human/STK3 GO:0090090 negative regulation of canonical Wnt signaling pathway ARBA:ARBA00027950 KEEP_AS_NON_CORE leaf (0) 0 human/STK36 GO:0007017 microtubule-based process ARBA:ARBA00026739 MODIFY very general (>200 descendants) 206 NEEDS_MORE_SPECIFIC true but uninformative replacement term The parent term is true - axoneme assembly is a descendant of GO:0007017 - but uninformative, and the specific child is already established for this gene by IMP. Replacing the generic machine-learned row with GO:0035082 axoneme assembly states what the microtubule involvement actually is. This is preferable to removal because the ARBA call is not wrong, only vague, and it is preferable to acceptance because nothing in the record would otherwise connect the generic term to the central-pair phenotype. human/STT3B GO:0006487 protein N-linked glycosylation ARBA:ARBA00085866 ACCEPT specific (1-20) 11 human/STT3B GO:0008250 oligosaccharyltransferase complex ARBA:ARBA00092378 ACCEPT specific (1-20) 2 human/STUB1 GO:0007165 signal transduction ARBA:ARBA00029050 KEEP_AS_NON_CORE very general (>200 descendants) 937 human/STUB1 GO:0030163 protein catabolic process ARBA:ARBA00027403 KEEP_AS_NON_CORE general (21-200) 66 human/STUB1 GO:0033554 cellular response to stress ARBA:ARBA00028184 KEEP_AS_NON_CORE very general (>200 descendants) 285 human/STX12 GO:0031410 cytoplasmic vesicle ARBA:ARBA00027190 KEEP_AS_NON_CORE very general (>200 descendants) 274 human/SUFU GO:0000122 negative regulation of transcription by RNA polymerase II ARBA:ARBA00029133 ACCEPT specific (1-20) 10 human/SUFU GO:0005829 cytosol ARBA:ARBA00029243 ACCEPT general (21-200) 73 human/SUFU GO:0007165 signal transduction ARBA:ARBA00029050 MODIFY very general (>200 descendants) 937 NEEDS_MORE_SPECIFIC true but uninformative replacement term The essence is right but the term is so general that it conveys nothing about this protein. SUFU is not a generic signal transducer: its entire documented role is one specific negative step in one specific pathway, and GOA already carries that precise term eight times with IBA, IDA, IEA, IMP and TAS evidence. The guideline that an IEA may legitimately be broader than the experimental picture does not stretch to a term this far up the hierarchy, because 'signal transduction' would be equally true of several thousand human proteins with no shared biology. Modifying rather than removing preserves the intent of the original assignment. human/SULT1A1 GO:0006790 sulfur compound metabolic process ARBA:ARBA00028021 MODIFY general (21-200) 190 NEEDS_MORE_SPECIFIC true but uninformative replacement term GO:0051923 sulfation is a direct descendant of GO:0006790 and is exactly what SULT1A1 does; the ancestor term adds no information and dilutes the annotation set. Replace with the specific child. human/SULT1B1 GO:0006790 sulfur compound metabolic process ARBA:ARBA00028021 MODIFY general (21-200) 190 NEEDS_MORE_SPECIFIC true but uninformative replacement term Not wrong, but uninformatively general - it is a distant ancestor of the specific process this enzyme carries out. The sulfation term already annotated to this gene should be used instead. human/SUN1 GO:0034993 meiotic nuclear membrane microtubule tethering complex ARBA:ARBA00084616 ACCEPT specific (1-20) 1 human/SUN1 GO:0090292 nuclear matrix anchoring at nuclear membrane ARBA:ARBA00087029 ACCEPT leaf (0) 0 human/SUN1 GO:0140444 cytoskeleton-nuclear membrane anchor activity ARBA:ARBA00086303 ACCEPT leaf (0) 0 human/SUN2 GO:0034993 meiotic nuclear membrane microtubule tethering complex ARBA:ARBA00084616 MODIFY specific (1-20) 1 TOO_SPECIFIC overreach replacement term SUN2 forms LINC complexes with KASH5 in meiocytes and contributes, partially redundantly with SUN1, to telomere attachment to the nuclear envelope. However most SUN2 function is in somatic LINC complexes, which GO represents by the non-meiotic parent GO:0106094. Replace with GO:0106094, which covers both contexts. human/SUN2 GO:0090292 nuclear matrix anchoring at nuclear membrane ARBA:ARBA00087029 ACCEPT leaf (0) 0 human/SUN2 GO:0140444 cytoskeleton-nuclear membrane anchor activity ARBA:ARBA00086303 ACCEPT leaf (0) 0 human/SUN5 GO:0007283 spermatogenesis ARBA:ARBA00085131 ACCEPT general (21-200) 28 human/SYN1 GO:0007268 chemical synaptic transmission ARBA:ARBA00028185 ACCEPT general (21-200) 69 human/SYN1 GO:0050804 modulation of chemical synaptic transmission ARBA:ARBA00029187 ACCEPT general (21-200) 116 human/SYN2 GO:0007268 chemical synaptic transmission ARBA:ARBA00028185 ACCEPT general (21-200) 69 human/SYN3 GO:0007268 chemical synaptic transmission ARBA:ARBA00028185 ACCEPT general (21-200) 69 human/SYN3 GO:0050804 modulation of chemical synaptic transmission ARBA:ARBA00029187 ACCEPT general (21-200) 116 human/SYNE1 GO:0003779 actin binding ARBA:ARBA00028548 ACCEPT specific (1-20) 3 human/SYNE1 GO:0034993 meiotic nuclear membrane microtubule tethering complex ARBA:ARBA00084616 MODIFY specific (1-20) 1 TOO_SPECIFIC overreach replacement term Nesprin-1 is a core KASH component of LINC complexes with SUN1/SUN2, but the evidence (somatic HeLa/fibroblast LINC disruption and SUN-KASH1 crystal structures) is not meiosis-specific, and nesprin-1 functions in interphase somatic cells (myonuclear anchorage, nuclear migration). The meiosis-specific child term is too narrow; the general nuclear membrane microtubule tethering complex term is appropriate. human/SYNE1 GO:0042802 identical protein binding ARBA:ARBA00027930 KEEP_AS_NON_CORE specific (1-20) 1 human/SYNE1 GO:0140444 cytoskeleton-nuclear membrane anchor activity ARBA:ARBA00086303 ACCEPT leaf (0) 0 human/SYNE2 GO:0007097 nuclear migration ARBA:ARBA00026920 ACCEPT specific (1-20) 18 human/SYNE2 GO:0034993 meiotic nuclear membrane microtubule tethering complex ARBA:ARBA00084616 MODIFY specific (1-20) 1 TOO_SPECIFIC overreach replacement term Nesprin-2 is a core KASH component of LINC complexes, but the evidence is from somatic cells (HeLa/fibroblasts, structural reconstitution) and its functions (nuclear movement, mechanotransduction, neuronal nucleokinesis) are interphase somatic functions. GO:0034993 is the meiosis-specific child; the non-meiotic parent GO:0106094 nuclear membrane microtubule tethering complex is the appropriate term. human/SYNE2 GO:0051642 centrosome localization ARBA:ARBA00090277 ACCEPT specific (1-20) 2 human/SYNE2 GO:0140444 cytoskeleton-nuclear membrane anchor activity ARBA:ARBA00086303 ACCEPT leaf (0) 0 human/SYNE3 GO:0031965 nuclear membrane ARBA:ARBA00086674 ACCEPT specific (1-20) 6 human/SYNE3 GO:0034993 meiotic nuclear membrane microtubule tethering complex ARBA:ARBA00084616 MODIFY specific (1-20) 1 TOO_SPECIFIC overreach replacement term Nesprin-3 is a KASH-domain subunit of LINC complexes, but all evidence comes from interphase somatic cells (HeLa, fibroblasts, endothelial cells, keratinocytes) and structural reconstitution with SUN2; there is no evidence for a meiotic role (the meiotic KASH protein is KASH5/CCDC155). GO:0034993 is the meiosis-specific child; consistent with the SUN1, SUN2, SYNE1 and SYNE2 reviews, the non-meiotic parent GO:0106094 nuclear membrane microtubule tethering complex is the appropriate complex term. human/SYVN1 GO:0044322 endoplasmic reticulum quality control compartment ARBA:ARBA00084770 ACCEPT leaf (0) 0 human/SYVN1 GO:0050821 protein stabilization ARBA:ARBA00033884 KEEP_AS_NON_CORE leaf (0) 0 human/SYVN1 GO:1902236 negative regulation of endoplasmic reticulum stress-induced intrinsic apoptotic signaling pathway ARBA:ARBA00089052 ACCEPT specific (1-20) 1 human/TACO1 GO:0070129 regulation of mitochondrial translation ARBA:ARBA00097059 ACCEPT specific (1-20) 7 human/TACO1 GO:0097177 mitochondrial ribosome binding ARBA:ARBA00097019 ACCEPT specific (1-20) 2 human/TARDBP GO:0003690 double-stranded DNA binding ARBA:ARBA00027852 ACCEPT general (21-200) 77 human/TAS2R38 GO:0005886 plasma membrane ARBA:ARBA00027801 ACCEPT very general (>200 descendants) 415 human/TBK1 GO:0002218 activation of innate immune response ARBA:ARBA00034386 ACCEPT general (21-200) 54 human/TBK1 GO:0006952 defense response ARBA:ARBA00026315 KEEP_AS_NON_CORE general (21-200) 175 human/TBK1 GO:0016239 positive regulation of macroautophagy ARBA:ARBA00086948 ACCEPT specific (1-20) 8 human/TBK1 GO:0032008 positive regulation of TOR signaling ARBA:ARBA00092062 KEEP_AS_NON_CORE specific (1-20) 2 human/TBK1 GO:0032728 positive regulation of interferon-beta production ARBA:ARBA00085789 ACCEPT leaf (0) 0 human/TBK1 GO:0043123 positive regulation of canonical NF-kappaB signal transduction ARBA:ARBA00026690 ACCEPT leaf (0) 0 human/TBK1 GO:0051707 response to other organism ARBA:ARBA00029118 KEEP_AS_NON_CORE general (21-200) 199 human/TBX20 GO:0003179 heart valve morphogenesis ARBA:ARBA00088519 KEEP_AS_NON_CORE specific (1-20) 18 human/TBX5 GO:0030326 embryonic limb morphogenesis ARBA:ARBA00087370 ACCEPT specific (1-20) 6 human/TBXT GO:1990837 sequence-specific double-stranded DNA binding ARBA:ARBA00028376 ACCEPT general (21-200) 48 human/TCP1 GO:0032212 positive regulation of telomere maintenance via telomerase ARBA:ARBA00047236 KEEP_AS_NON_CORE leaf (0) 0 human/TCP1 GO:0044183 protein folding chaperone ARBA:ARBA00029119 MODIFY specific (1-20) 1 NEEDS_MORE_SPECIFIC true but uninformative replacement term This is correct but less specific than the ATP-dependent chaperonin activity. human/TFR2 GO:0006898 receptor-mediated endocytosis ARBA:ARBA00044584 ACCEPT general (21-200) 30 human/TFR2 GO:0009897 external side of plasma membrane ARBA:ARBA00043397 ACCEPT specific (1-20) 4 human/TFR2 GO:0060586 multicellular organismal-level iron ion homeostasis ARBA:ARBA00092899 ACCEPT leaf (0) 0 human/TFRC GO:0006898 receptor-mediated endocytosis ARBA:ARBA00044584 ACCEPT general (21-200) 30 human/TFRC GO:0060586 multicellular organismal-level iron ion homeostasis ARBA:ARBA00092899 ACCEPT leaf (0) 0 human/TH GO:0043005 neuron projection ARBA:ARBA00027418 ACCEPT general (21-200) 135 human/THBS1 GO:0001937 negative regulation of endothelial cell proliferation ARBA:ARBA00091247 ACCEPT specific (1-20) 2 human/THBS1 GO:0002684 positive regulation of immune system process ARBA:ARBA00027011 MARK_AS_OVER_ANNOTATED very general (>200 descendants) 392 TOO_GENERAL true but uninformative broad This annotation is too broad and somewhat misleading. TSP1's predominant role is immunosuppressive - it negatively regulates IL-12, TNF-alpha, and IL-10 production through CD47/CD36 signaling and limits T-cell/NK cell activation. While TSP1 can enhance certain immune responses in specific contexts, this broad positive regulation term does not accurately capture TSP1's function. human/THBS1 GO:0010810 regulation of cell-substrate adhesion ARBA:ARBA00084900 ACCEPT general (21-200) 22 human/THBS1 GO:0030335 positive regulation of cell migration ARBA:ARBA00028907 ACCEPT general (21-200) 68 human/THBS1 GO:0030511 positive regulation of transforming growth factor beta receptor signaling pathway ARBA:ARBA00086893 ACCEPT leaf (0) 0 human/THBS1 GO:0031012 extracellular matrix ARBA:ARBA00027396 ACCEPT general (21-200) 104 human/THBS1 GO:0031091 platelet alpha granule ARBA:ARBA00084785 ACCEPT specific (1-20) 2 human/THBS1 GO:0048514 blood vessel morphogenesis ARBA:ARBA00091782 ACCEPT general (21-200) 56 human/THBS1 GO:0050840 extracellular matrix binding ARBA:ARBA00091797 ACCEPT specific (1-20) 7 human/THBS1 GO:0050921 positive regulation of chemotaxis ARBA:ARBA00091297 ACCEPT general (21-200) 32 human/THBS2 GO:0031091 platelet alpha granule ARBA:ARBA00084785 UNDECIDED specific (1-20) 2 human/THBS4 GO:0008201 heparin binding ARBA:ARBA00027326 ACCEPT leaf (0) 0 human/THG1L GO:0008033 tRNA processing ARBA:ARBA00029020 ACCEPT general (21-200) 79 human/THTPA GO:0005829 cytosol ARBA:ARBA00029243 ACCEPT general (21-200) 73 human/THTPA GO:0042723 thiamine-containing compound metabolic process ARBA:ARBA00028583 KEEP_AS_NON_CORE specific (1-20) 12 human/TIAL1 GO:0003730 mRNA 3'-UTR binding ARBA:ARBA00028422 ACCEPT specific (1-20) 1 human/TIAL1 GO:0042127 regulation of cell population proliferation ARBA:ARBA00027546 MODIFY very general (>200 descendants) 258 NEEDS_MORE_SPECIFIC true but uninformative replacement term The Rox8/TIAR study supports a directional effect through YAP/yki mRNA destabilization and suppression of tissue overgrowth. The existing experimentally supported negative-regulation term is more informative than this undirected parent. human/TICAM1 GO:0007166 cell surface receptor signaling pathway ARBA:ARBA00029053 MARK_AS_OVER_ANNOTATED very general (>200 descendants) 403 INDIRECT_EFFECT overreach downstream GO:0002224 toll-like receptor signaling pathway is not classified under cell surface receptor signaling pathway (checked in OLS). TICAM1 signals mainly downstream of endosomal TLR3 and of TLR4 after internalization into endosomes, so the cell-surface framing is misleading; the TLR pathway terms capture the process correctly. human/TICAM1 GO:0032481 positive regulation of type I interferon production ARBA:ARBA00049826 ACCEPT specific (1-20) 2 human/TICAM1 GO:0043330 response to exogenous dsRNA ARBA:ARBA00043583 ACCEPT specific (1-20) 2 human/TICAM1 GO:0060090 molecular adaptor activity ARBA:ARBA00026447 MODIFY general (21-200) 176 NEEDS_MORE_SPECIFIC true but uninformative replacement term Molecular adaptor activity is correct but a generic parent; the more specific GO:0035591 signaling adaptor activity (a child of molecular adaptor activity, checked in OLS) describes TICAM1 bridging receptors to signaling effectors. human/TIMM44 GO:0045184 establishment of protein localization ARBA:ARBA00027110 MARK_AS_OVER_ANNOTATED general (21-200) 176 TOO_GENERAL true but uninformative generic Use mitochondrial matrix import and PAM adaptor/chaperone-binding terms instead of generic establishment of protein localization. human/TIMM50 GO:0004722 protein serine/threonine phosphatase activity ARBA:ARBA00027653 KEEP_AS_NON_CORE specific (1-20) 11 human/TKT GO:0016744 transketolase or transaldolase activity ARBA:ARBA00027716 MARK_AS_OVER_ANNOTATED specific (1-20) 10 TOO_GENERAL true but uninformative general "The disjunctive ""transketolase or transaldolase activity"" term is less informative than the demonstrated transketolase activity (GO:0004802). It is not wrong but is an over-general ARBA-derived assignment superseded by the specific term." human/TKT GO:0019682 glyceraldehyde-3-phosphate metabolic process ARBA:ARBA00047264 KEEP_AS_NON_CORE specific (1-20) 4 human/TLN1 GO:0007043 cell-cell junction assembly ARBA:ARBA00092055 MODIFY specific (1-20) 14 OTHER_TERM different term needed replacement term Talin assembles integrin-mediated junctions with the extracellular matrix, not cell-cell junctions; the cell-cell term is a misdirected generalization. Focal adhesion assembly captures the process talin actually performs. human/TLR1 GO:0043235 signaling receptor complex ARBA:ARBA00029086 ACCEPT general (21-200) 113 human/TLR10 GO:0043235 signaling receptor complex ARBA:ARBA00029086 KEEP_AS_NON_CORE general (21-200) 113 human/TLR2 GO:0043235 signaling receptor complex ARBA:ARBA00029086 ACCEPT general (21-200) 113 human/TLR3 GO:0002682 regulation of immune system process ARBA:ARBA00027003 KEEP_AS_NON_CORE very general (>200 descendants) 1028 human/TLR3 GO:0032722 positive regulation of chemokine production ARBA:ARBA00085792 KEEP_AS_NON_CORE specific (1-20) 13 human/TLR3 GO:0035556 intracellular signal transduction ARBA:ARBA00026887 KEEP_AS_NON_CORE general (21-200) 195 human/TLR3 GO:0043123 positive regulation of canonical NF-kappaB signal transduction ARBA:ARBA00026690 ACCEPT leaf (0) 0 human/TLR3 GO:0043330 response to exogenous dsRNA ARBA:ARBA00043583 ACCEPT specific (1-20) 2 human/TLR3 GO:0046330 positive regulation of JNK cascade ARBA:ARBA00093162 KEEP_AS_NON_CORE leaf (0) 0 human/TLR4 GO:0045321 leukocyte activation ARBA:ARBA00091994 KEEP_AS_NON_CORE general (21-200) 181 human/TLR6 GO:0043235 signaling receptor complex ARBA:ARBA00029086 ACCEPT general (21-200) 113 human/TLR7 GO:0006952 defense response ARBA:ARBA00026315 KEEP_AS_NON_CORE general (21-200) 175 human/TLR7 GO:0006955 immune response ARBA:ARBA00026313 KEEP_AS_NON_CORE very general (>200 descendants) 207 human/TLR7 GO:0032728 positive regulation of interferon-beta production ARBA:ARBA00085789 ACCEPT leaf (0) 0 human/TLR7 GO:0032729 positive regulation of type II interferon production ARBA:ARBA00085791 KEEP_AS_NON_CORE leaf (0) 0 human/TLR7 GO:0032757 positive regulation of interleukin-8 production ARBA:ARBA00085873 ACCEPT leaf (0) 0 human/TLR7 GO:0036020 endolysosome membrane ARBA:ARBA00090222 ACCEPT leaf (0) 0 human/TLR7 GO:0051707 response to other organism ARBA:ARBA00029118 KEEP_AS_NON_CORE general (21-200) 199 human/TLR7 GO:0140894 endolysosomal toll-like receptor signaling pathway ARBA:ARBA00087274 ACCEPT specific (1-20) 7 human/TLR8 GO:0006952 defense response ARBA:ARBA00026315 KEEP_AS_NON_CORE general (21-200) 175 human/TLR8 GO:0006955 immune response ARBA:ARBA00026313 KEEP_AS_NON_CORE very general (>200 descendants) 207 human/TLR8 GO:0032727 positive regulation of interferon-alpha production ARBA:ARBA00085788 ACCEPT leaf (0) 0 human/TLR8 GO:0032728 positive regulation of interferon-beta production ARBA:ARBA00085789 ACCEPT leaf (0) 0 human/TLR8 GO:0032729 positive regulation of type II interferon production ARBA:ARBA00085791 MARK_AS_OVER_ANNOTATED leaf (0) 0 INDIRECT_EFFECT overreach indirect No TLR8-specific IFN-gamma evidence appears in the literature reviewed here. Unlike TLR7, where loss-of-function patients show an IFN-gamma defect, TLR8 stimulation is characterised by IL-1beta, IL-6, IL-12, TNF and type I interferon; IFN-gamma after TLR8 ligation would arise indirectly from NK and T cells responding to those cytokines. Over-annotation, consistent with the TLR9 review. human/TLR8 GO:0032757 positive regulation of interleukin-8 production ARBA:ARBA00085873 ACCEPT leaf (0) 0 human/TLR8 GO:0036020 endolysosome membrane ARBA:ARBA00090222 MODIFY leaf (0) 0 OTHER_TERM different term needed replacement term The compartment is one step too far along the endocytic route for TLR8. Endogenous TLR8 in human monocytes and in HeLa transfectants colocalised with the early-endosome marker EEA1 and with an ER marker, but not with late-endosome or lysosome markers, and the authors drew the contrast with TLR7 and TLR9 explicitly. Early endosome membrane (GO:0031901) is the supported location; endosome membrane (GO:0010008), which TLR8 also carries, is correct as a parent. human/TLR8 GO:0043123 positive regulation of canonical NF-kappaB signal transduction ARBA:ARBA00026690 ACCEPT leaf (0) 0 human/TLR8 GO:0051707 response to other organism ARBA:ARBA00029118 KEEP_AS_NON_CORE general (21-200) 199 human/TLR8 GO:0140894 endolysosomal toll-like receptor signaling pathway ARBA:ARBA00087274 ACCEPT specific (1-20) 7 human/TLR9 GO:0006952 defense response ARBA:ARBA00026315 KEEP_AS_NON_CORE general (21-200) 175 human/TLR9 GO:0006955 immune response ARBA:ARBA00026313 KEEP_AS_NON_CORE very general (>200 descendants) 207 human/TLR9 GO:0032727 positive regulation of interferon-alpha production ARBA:ARBA00085788 ACCEPT leaf (0) 0 human/TLR9 GO:0032729 positive regulation of type II interferon production ARBA:ARBA00085791 MARK_AS_OVER_ANNOTATED leaf (0) 0 INDIRECT_EFFECT overreach indirect IFN-gamma production after CpG stimulation arises largely indirectly (e.g. NK or T cells responding to cytokines from TLR9-expressing cells). No direct evidence in the cached literature for TLR9 driving IFN-gamma; over-annotation. human/TLR9 GO:0032757 positive regulation of interleukin-8 production ARBA:ARBA00085873 KEEP_AS_NON_CORE leaf (0) 0 human/TLR9 GO:0036020 endolysosome membrane ARBA:ARBA00090222 ACCEPT leaf (0) 0 human/TLR9 GO:0043123 positive regulation of canonical NF-kappaB signal transduction ARBA:ARBA00026690 ACCEPT leaf (0) 0 human/TLR9 GO:0051707 response to other organism ARBA:ARBA00029118 KEEP_AS_NON_CORE general (21-200) 199 human/TLR9 GO:0140894 endolysosomal toll-like receptor signaling pathway ARBA:ARBA00087274 ACCEPT specific (1-20) 7 human/TNFAIP3 GO:0002376 immune system process ARBA:ARBA00027799 ACCEPT very general (>200 descendants) 673 human/TNFAIP3 GO:0019899 enzyme binding ARBA:ARBA00026481 ACCEPT general (21-200) 77 human/TNFAIP3 GO:0039532 negative regulation of cytoplasmic pattern recognition receptor signaling pathway ARBA:ARBA00089226 ACCEPT specific (1-20) 17 human/TNFAIP3 GO:0042127 regulation of cell population proliferation ARBA:ARBA00027546 MARK_AS_OVER_ANNOTATED very general (>200 descendants) 258 INDIRECT_EFFECT overreach indirect Overly broad annotation. While A20 affects proliferation indirectly through NF-kB, this is not a direct molecular function. More specific proliferation annotations (smooth muscle cell, hepatocyte) are present. human/TNFAIP3 GO:0045732 positive regulation of protein catabolic process ARBA:ARBA00026548 ACCEPT specific (1-20) 13 human/TNFAIP3 GO:0070536 protein K63-linked deubiquitination ARBA:ARBA00085190 ACCEPT leaf (0) 0 human/TNFAIP3 GO:1901701 cellular response to oxygen-containing compound ARBA:ARBA00027483 MARK_AS_OVER_ANNOTATED very general (>200 descendants) 308 TOO_GENERAL true but uninformative broad Overly broad. More specific cellular response to hydrogen peroxide is annotated. This broad parent does not add useful information. human/TNFRSF10A GO:0005035 death receptor activity ARBA:ARBA00086160 MODIFY specific (1-20) 2 NEEDS_MORE_SPECIFIC true but uninformative replacement term TNFRSF10A is the TRAIL-binding death receptor whose cytoplasmic death domain nucleates FADD- and CASP8-containing DISC assembly; GO:0036463 captures that receptor specificity better than the parent death receptor term. human/TNFRSF10A GO:0009986 cell surface ARBA:ARBA00027349 ACCEPT specific (1-20) 14 human/TNFRSF10A GO:0036462 TRAIL-activated apoptotic signaling pathway ARBA:ARBA00089691 ACCEPT specific (1-20) 2 human/TNFRSF10A GO:0071260 cellular response to mechanical stimulus ARBA:ARBA00092880 MARK_AS_OVER_ANNOTATED leaf (0) 0 UNCLASSIFIED unclassified The linked experimental row is only expression-pattern evidence from a prostate-cancer BAD study and should not be propagated as a DR4 apoptotic function. human/TNFRSF10B GO:0005035 death receptor activity ARBA:ARBA00086160 MODIFY specific (1-20) 2 NEEDS_MORE_SPECIFIC true but uninformative replacement term DR5 is a TRAIL-binding death receptor whose cytoplasmic death domain recruits FADD and initiator caspases; GO:0036463 captures the ligand specificity and receptor signaling activity. human/TNFRSF10B GO:0005886 plasma membrane ARBA:ARBA00027801 ACCEPT very general (>200 descendants) 415 human/TNFRSF10B GO:0009986 cell surface ARBA:ARBA00027349 ACCEPT specific (1-20) 14 human/TNFRSF10B GO:0036462 TRAIL-activated apoptotic signaling pathway ARBA:ARBA00089691 ACCEPT specific (1-20) 2 human/TNFRSF10B GO:0071260 cellular response to mechanical stimulus ARBA:ARBA00092880 MARK_AS_OVER_ANNOTATED leaf (0) 0 INDIRECT_EFFECT overreach Expression change Expression change under cyclic stretch does not show that DR5 performs the cellular response to mechanical stimulus. human/TNFRSF1A GO:0010468 regulation of gene expression ARBA:ARBA00028334 MARK_AS_OVER_ANNOTATED very general (>200 descendants) 874 TOO_GENERAL true but uninformative broad "Regulation of gene expression is an extremely broad term. While TNFR1 does activate NF-kappaB which is a transcription factor, annotating the receptor itself to ""regulation of gene expression"" is too distant from the receptor's direct molecular role. The annotation chain is receptor -> adaptors -> kinase cascades -> IKK -> NF-kappaB -> gene expression. More specific annotations (positive regulation of NF-kappaB signaling, positive regulation of transcription by RNA pol II) are already present." human/TNFRSF1A GO:0010557 positive regulation of macromolecule biosynthetic process ARBA:ARBA00027412 MARK_AS_OVER_ANNOTATED very general (>200 descendants) 270 TOO_GENERAL true but uninformative broad This is an extremely broad term. While TNFR1 signaling via NF-kappaB can promote transcription and thus macromolecule biosynthesis, this annotation provides no useful specificity about TNFR1 function. More specific terms are already annotated. human/TNFRSF1A GO:0050793 regulation of developmental process ARBA:ARBA00028689 MARK_AS_OVER_ANNOTATED very general (>200 descendants) 1542 INDIRECT_EFFECT overreach indirect While TNFR1 has roles in developmental apoptosis (valve development, morphogenesis), those are annotated with more specific terms. This very broad IEA term does not add useful information and is likely derived from indirect pathway annotations. human/TNFRSF1A GO:0051239 regulation of multicellular organismal process ARBA:ARBA00028859 MARK_AS_OVER_ANNOTATED very general (>200 descendants) 1807 TOO_GENERAL true but uninformative broad This is one of the broadest possible BP annotations. While technically not wrong, it provides no useful information about TNFR1 function. More specific process terms are already annotated. human/TNFSF10 GO:0005102 signaling receptor binding ARBA:ARBA00027239 MODIFY very general (>200 descendants) 380 NEEDS_MORE_SPECIFIC true but uninformative replacement term Use tumor necrosis factor receptor binding to capture the TNFRSF10 receptor-ligand activity supported by the original Apo2L/TRAIL discovery papers and later DR4/DR5 structural work. human/TNFSF10 GO:0007154 cell communication ARBA:ARBA00028945 MODIFY very general (>200 descendants) 1207 NEEDS_MORE_SPECIFIC true but uninformative replacement term Use GO:0036462 to name the ligand-specific death-receptor pathway initiated by TNFSF10. human/TNFSF10 GO:0023052 signaling ARBA:ARBA00026303 MODIFY very general (>200 descendants) 1141 NEEDS_MORE_SPECIFIC true but uninformative replacement term Use GO:0036462 to name the ligand-specific death-receptor pathway initiated by TNFSF10. human/TNFSF10 GO:2001238 positive regulation of extrinsic apoptotic signaling pathway ARBA:ARBA00087870 ACCEPT specific (1-20) 3 human/TNKS GO:0000209 protein polyubiquitination ARBA:ARBA00044436 MODIFY specific (1-20) 9 OTHER_TERM different term needed replacement term TNKS does not function as the E3 ubiquitin ligase; it PARylates substrates that are then recognized by PAR-binding ubiquitin ligases such as RNF146. human/TNKS GO:0000242 pericentriolar material ARBA:ARBA00090148 ACCEPT leaf (0) 0 human/TNKS GO:0005635 nuclear envelope ARBA:ARBA00026328 KEEP_AS_NON_CORE general (21-200) 29 human/TNKS GO:0032212 positive regulation of telomere maintenance via telomerase ARBA:ARBA00047236 ACCEPT leaf (0) 0 human/TNKS GO:0070198 protein localization to chromosome, telomeric region ARBA:ARBA00092227 ACCEPT specific (1-20) 1 human/TNKS GO:0070212 protein poly-ADP-ribosylation ARBA:ARBA00092423 ACCEPT leaf (0) 0 human/TNKS GO:0070213 protein auto-ADP-ribosylation ARBA:ARBA00092422 ACCEPT leaf (0) 0 human/TNKS GO:0090263 positive regulation of canonical Wnt signaling pathway ARBA:ARBA00087063 ACCEPT leaf (0) 0 human/TNKS GO:1904355 positive regulation of telomere capping ARBA:ARBA00089794 ACCEPT leaf (0) 0 human/TNKS GO:1904357 negative regulation of telomere maintenance via telomere lengthening ARBA:ARBA00089789 MARK_AS_OVER_ANNOTATED specific (1-20) 1 UNCLASSIFIED unclassified Canonical TNKS/TRF1 evidence supports release of TRF1 from telomeres and promotion of telomere elongation; the negative-direction annotation should not be accepted without context-specific evidence. human/TNKS GO:1990404 NAD+-protein mono-ADP-ribosyltransferase activity ARBA:ARBA00049855 ACCEPT specific (1-20) 13 human/TOP2A GO:0003682 chromatin binding ARBA:ARBA00027831 ACCEPT specific (1-20) 10 human/TOP2A GO:0045870 positive regulation of single stranded viral RNA replication via double stranded DNA intermediate ARBA:ARBA00086549 KEEP_AS_NON_CORE leaf (0) 0 human/TOP2B GO:0003682 chromatin binding ARBA:ARBA00027831 ACCEPT specific (1-20) 10 human/TOP2B GO:0045870 positive regulation of single stranded viral RNA replication via double stranded DNA intermediate ARBA:ARBA00086549 KEEP_AS_NON_CORE leaf (0) 0 human/TP53 GO:0010212 response to ionizing radiation ARBA:ARBA00090590 ACCEPT specific (1-20) 5 human/TP53 GO:0051053 negative regulation of DNA metabolic process ARBA:ARBA00088036 ACCEPT general (21-200) 61 human/TP53 GO:0071456 cellular response to hypoxia ARBA:ARBA00092776 ACCEPT specific (1-20) 2 human/TP53 GO:0097190 apoptotic signaling pathway ARBA:ARBA00028296 ACCEPT general (21-200) 28 human/TP53 GO:2001242 regulation of intrinsic apoptotic signaling pathway ARBA:ARBA00087888 ACCEPT general (21-200) 38 human/TPK1 GO:0005829 cytosol ARBA:ARBA00029243 ACCEPT general (21-200) 73 human/TPM1 GO:0005862 muscle thin filament tropomyosin ARBA:ARBA00088171 ACCEPT leaf (0) 0 human/TPM3 GO:0005862 muscle thin filament tropomyosin ARBA:ARBA00088171 KEEP_AS_NON_CORE leaf (0) 0 human/TRAF2 GO:0002700 regulation of production of molecular mediator of immune response ARBA:ARBA00090360 ACCEPT general (21-200) 97 human/TRAF2 GO:0010628 positive regulation of gene expression ARBA:ARBA00026655 KEEP_AS_NON_CORE general (21-200) 198 human/TRAF2 GO:0012501 programmed cell death ARBA:ARBA00028943 KEEP_AS_NON_CORE general (21-200) 147 human/TRAF2 GO:0019899 enzyme binding ARBA:ARBA00026481 ACCEPT general (21-200) 77 human/TRAF2 GO:0030674 protein-macromolecule adaptor activity ARBA:ARBA00026473 ACCEPT general (21-200) 91 human/TRAF2 GO:0032813 tumor necrosis factor receptor superfamily binding ARBA:ARBA00085459 ACCEPT specific (1-20) 5 human/TRAF2 GO:0042802 identical protein binding ARBA:ARBA00027930 ACCEPT specific (1-20) 1 human/TRAF2 GO:0043235 signaling receptor complex ARBA:ARBA00029086 ACCEPT general (21-200) 113 human/TRAF2 GO:0043408 regulation of MAPK cascade ARBA:ARBA00027210 ACCEPT general (21-200) 28 human/TRAF3 GO:0016020 membrane ARBA:ARBA00028763 REMOVE very general (>200 descendants) 895 WRONG_LOCATION wrong manual WRONG_LOCATION TRAF3 has no transmembrane segment, signal peptide or lipid anchor; it is a soluble cytosolic protein transiently recruited to membrane-proximal complexes. That recruitment is already captured precisely by GO:0009898 (cytoplasmic side of plasma membrane) and GO:0010008 (endosome membrane), so the bare parent adds no information and implies membrane residence that is not the case. human/TRAF3 GO:0031625 ubiquitin protein ligase binding ARBA:ARBA00028807 KEEP_AS_NON_CORE leaf (0) 0 human/TRAF3 GO:0031996 thioesterase binding ARBA:ARBA00026509 KEEP_AS_NON_CORE leaf (0) 0 human/TRAF3 GO:0032479 regulation of type I interferon production ARBA:ARBA00049827 MODIFY specific (1-20) 8 NEEDS_MORE_SPECIFIC true but uninformative replacement term TRAF3's role in this pathway is unambiguously positive and is directly demonstrated, so the signed child GO:0032481 should be used instead of the unsigned parent. human/TRAF3 GO:0042802 identical protein binding ARBA:ARBA00027930 KEEP_AS_NON_CORE specific (1-20) 1 human/TRAF6 GO:0019899 enzyme binding ARBA:ARBA00026481 ACCEPT general (21-200) 77 human/TRAF6 GO:0042802 identical protein binding ARBA:ARBA00027930 ACCEPT specific (1-20) 1 human/TRAF6 GO:0032991 protein-containing complex ARBA:ARBA00028902 ACCEPT very general (>200 descendants) 2083 human/TRAF6 GO:0141124 intracellular signaling cassette ARBA:ARBA00044593 KEEP_AS_NON_CORE general (21-200) 68 human/TRAF6 GO:1901701 cellular response to oxygen-containing compound ARBA:ARBA00027483 KEEP_AS_NON_CORE very general (>200 descendants) 308 human/TRAPPC1 GO:0005737 cytoplasm ARBA:ARBA00026971 ACCEPT very general (>200 descendants) 1146 human/TRAPPC4 GO:0005737 cytoplasm ARBA:ARBA00026971 ACCEPT very general (>200 descendants) 1146 human/TREM2 GO:0004888 transmembrane signaling receptor activity ARBA:ARBA00026973 ACCEPT very general (>200 descendants) 327 human/TREM2 GO:0006909 phagocytosis ARBA:ARBA00027650 ACCEPT specific (1-20) 15 human/TREM2 GO:0008289 lipid binding ARBA:ARBA00027537 ACCEPT general (21-200) 94 human/TREM2 GO:0035176 social behavior ARBA:ARBA00091504 KEEP_AS_NON_CORE specific (1-20) 2 human/TREM2 GO:0048468 cell development ARBA:ARBA00028665 KEEP_AS_NON_CORE very general (>200 descendants) 672 human/TREM2 GO:0050850 positive regulation of calcium-mediated signaling ARBA:ARBA00091707 ACCEPT specific (1-20) 3 human/TREM2 GO:0071396 cellular response to lipid ARBA:ARBA00027803 ACCEPT general (21-200) 91 human/TREM2 GO:0097367 carbohydrate derivative binding ARBA:ARBA00026523 KEEP_AS_NON_CORE general (21-200) 89 human/TREM2 GO:1900226 negative regulation of NLRP3 inflammasome complex assembly ARBA:ARBA00090488 KEEP_AS_NON_CORE leaf (0) 0 human/TRIM17 GO:0004842 ubiquitin-protein transferase activity ARBA:ARBA00026878 ACCEPT specific (1-20) 18 human/TRIM17 GO:0051865 protein autoubiquitination ARBA:ARBA00089741 ACCEPT leaf (0) 0 human/TRIM5 GO:0042802 identical protein binding ARBA:ARBA00027930 KEEP_AS_NON_CORE specific (1-20) 1 human/TRMT61A GO:0006396 RNA processing ARBA:ARBA00028223 MODIFY very general (>200 descendants) 252 NEEDS_MORE_SPECIFIC true but uninformative replacement term Correct in kind but far too general to be useful. GO:0030488 tRNA methylation is a descendant of GO:0006396 (verified against the QuickGO ancestors endpoint) and is already carried by this gene with better evidence, so the specific term should stand in its place. human/TSG101 GO:0000813 ESCRT I complex ARBA:ARBA00026622 ACCEPT leaf (0) 0 human/TSG101 GO:0006355 regulation of DNA-templated transcription ARBA:ARBA00028138 MARK_AS_OVER_ANNOTATED general (21-200) 140 UNCLASSIFIED unclassified The synthesized evidence supports ESCRT-I ubiquitin/cargo sorting and membrane scission; DNA/transcription terms are not central and are not well integrated with the current proteostasis review. human/TSG101 GO:0016236 macroautophagy ARBA:ARBA00027245 MODIFY general (21-200) 34 NEEDS_MORE_SPECIFIC true but uninformative replacement term The best-supported PN autophagy interpretation is ESCRT-I-mediated phagophore/autophagosome closure, which is better represented by autophagosome assembly. human/TSG101 GO:0036258 multivesicular body assembly ARBA:ARBA00027035 ACCEPT leaf (0) 0 human/TSG101 GO:0039702 viral budding via host ESCRT complex ARBA:ARBA00028526 KEEP_AS_NON_CORE leaf (0) 0 human/TTBK2 GO:0015630 microtubule cytoskeleton ARBA:ARBA00029268 KEEP_AS_NON_CORE general (21-200) 108 human/TTBK2 GO:0050321 tau-protein kinase activity ARBA:ARBA00090286 KEEP_AS_NON_CORE leaf (0) 0 human/TTC21B GO:0010468 regulation of gene expression ARBA:ARBA00028334 MARK_AS_OVER_ANNOTATED very general (>200 descendants) 874 INDIRECT_EFFECT overreach indirect Machine-learned annotation with no direct basis; any effect of TTC21B on gene expression is indirect, downstream of ciliary Hedgehog-pathway trafficking. human/TTC21B GO:0061512 protein localization to cilium ARBA:ARBA00091714 ACCEPT specific (1-20) 8 human/TTC8 GO:0007600 sensory perception ARBA:ARBA00027936 MARK_AS_OVER_ANNOTATED general (21-200) 81 INDIRECT_EFFECT overreach phenotype Distal phenotype-level term from electronic inference; not a direct function. human/TTC8 GO:0009653 anatomical structure morphogenesis ARBA:ARBA00026583 MARK_AS_OVER_ANNOTATED very general (>200 descendants) 1501 TOO_GENERAL true but uninformative general Overly general electronic annotation with no specific functional content. human/TTK GO:0000280 nuclear division ARBA:ARBA00028466 MODIFY general (21-200) 120 NEEDS_MORE_SPECIFIC true but uninformative replacement term Not wrong, but far too general to convey what TTK does; the mitotic-specific descendants already carried by GOA (mitotic spindle assembly checkpoint signaling, repair of mitotic kinetochore microtubule attachment defect) are the informative terms and are recommended in its place. human/TTK GO:0098813 nuclear chromosome segregation ARBA:ARBA00027947 KEEP_AS_NON_CORE general (21-200) 80 human/TUSC3 GO:0006487 protein N-linked glycosylation ARBA:ARBA00085866 ACCEPT specific (1-20) 11 human/TUSC3 GO:0008250 oligosaccharyltransferase complex ARBA:ARBA00092378 ACCEPT specific (1-20) 2 human/TUSC3 GO:0015095 magnesium ion transmembrane transporter activity ARBA:ARBA00026593 REMOVE specific (1-20) 2 WRONG_ACTIVITY wrong manual WRONG_ACTIVITY "This is a clearly-wrong electronic (IEA/ARBA) molecular-function assignment. TUSC3 is an ER OST-B oxidoreductase subunit; the Mg2+ transporter-activity MF conflicts with the mechanistic evidence and UniProt only states it ""Could indirectly play a role in Mg(2+) transport."" REMOVE is appropriate for an unsupported IEA MF (not applied to the experimental Mg2+ annotation, which is kept below)." human/TXN GO:0019725 cellular homeostasis ARBA:ARBA00027105 MODIFY general (21-200) 125 NEEDS_MORE_SPECIFIC true but uninformative replacement term While Trx1 does contribute to cellular homeostasis, the more specific and accurate term is GO:0045454 (cell redox homeostasis), which precisely describes the function of the thioredoxin system. human/TYMP GO:0055086 nucleobase-containing small molecule metabolic process ARBA:ARBA00027681 MARK_AS_OVER_ANNOTATED very general (>200 descendants) 576 TOO_GENERAL true but uninformative uninformative Thymidine, deoxyuridine, thymine and uracil are nucleobase-containing small molecules, so the term is an accurate ancestor, but it is uninformative relative to GO:0006213 and GO:0006206 which are already annotated. human/TYMP GO:0072527 pyrimidine-containing compound metabolic process ARBA:ARBA00026859 MARK_AS_OVER_ANNOTATED general (21-200) 139 TOO_GENERAL true but uninformative more specific This is a direct ancestor of the more specific pyrimidine nucleoside (GO:0006213) and nucleobase (GO:0006206) metabolic process terms that already capture TYMP's role; the broad term adds no specific information. human/TYMP GO:1901135 carbohydrate derivative metabolic process ARBA:ARBA00026297 MARK_AS_OVER_ANNOTATED very general (>200 descendants) 637 TOO_GENERAL true but uninformative general The 2-deoxy-alpha-D-ribose 1-phosphate product is a carbohydrate derivative, so the term is technically compatible, but it is far too general to convey TYMP's function; the specific pyrimidine metabolic process terms are preferred. human/UAP1 GO:0016772 transferase activity, transferring phosphorus-containing groups ARBA:ARBA00026261 MARK_AS_OVER_ANNOTATED very general (>200 descendants) 567 TOO_GENERAL true but uninformative High-level High-level parent term (ARBA). The specific activity (UDP-N-acetylglucosamine diphosphorylase, GO:0003977, a nucleotidyltransferase) is already captured with experimental evidence, so this general grouping term is an over-annotation. human/UBE2T GO:0019787 ubiquitin-like protein transferase activity ARBA:ARBA00027363 ACCEPT general (21-200) 48 human/UBE2T GO:0032446 protein modification by small protein conjugation ARBA:ARBA00026720 ACCEPT general (21-200) 24 human/UCKL1 GO:0008655 pyrimidine-containing compound salvage ARBA:ARBA00084547 ACCEPT specific (1-20) 14 human/UCKL1 GO:0055086 nucleobase-containing small molecule metabolic process ARBA:ARBA00027681 MARK_AS_OVER_ANNOTATED very general (>200 descendants) 576 TOO_GENERAL true but uninformative More specific More specific accepted terms for pyrimidine nucleoside, UMP, and CTP salvage capture the supported biology without the loss of information inherent in this ARBA parent. human/UCKL1 GO:1901137 carbohydrate derivative biosynthetic process ARBA:ARBA00026302 MARK_AS_OVER_ANNOTATED very general (>200 descendants) 296 UNCLASSIFIED unclassified The ARBA inference is not false, but UMP and CTP salvage terms describe the supported process at the appropriate specificity. human/UFD1 GO:0030970 retrograde protein transport, ER to cytosol ARBA:ARBA00087984 ACCEPT leaf (0) 0 human/UGGT1 GO:1904380 endoplasmic reticulum mannose trimming ARBA:ARBA00089809 REMOVE specific (1-20) 1 ROLE_CONFUSION wrong manual ROLE_CONFUSION UGGT1 does not perform mannose trimming. It is a glucosyltransferase that adds glucose to Man9GlcNAc2 N-glycans on misfolded glycoproteins. Mannose trimming is carried out by distinct enzymes (ERManI/MAN1B1, EDEM1/2/3) that act in the ERQC pathway. While UGGT1 operates in the same pathway as the mannose trimming enzymes, it performs an entirely different enzymatic reaction (glucosylation, not demannosylation). This is an incorrect ARBA prediction. human/UGT8 GO:0007399 nervous system development ARBA:ARBA00027428 KEEP_AS_NON_CORE very general (>200 descendants) 913 human/ULK1 GO:0006914 autophagy ARBA:ARBA00027757 ACCEPT general (21-200) 49 human/ULK1 GO:0034045 phagophore assembly site membrane ARBA:ARBA00091427 MODIFY specific (1-20) 2 OTHER_TERM different term needed replacement term Live QuickGO marks GO:0034045 obsolete and provides GO:7770114 phagophore membrane. Preserve the membrane claim with that current term. Original PMID:18936157 describes CTD-dependent membrane association; PMID:22885598 establishes LIR-mediated targeting and PMID:39169022 shows palmitoylation-dependent anchoring. The previous absence-of-a-membrane-binding-domain argument was factually wrong; a soluble kinase can bind a membrane. human/UMPS GO:0006222 UMP biosynthetic process ARBA:ARBA00086365 ACCEPT specific (1-20) 3 human/UNC119B GO:0042953 lipoprotein transport ARBA:ARBA00087852 ACCEPT leaf (0) 0 human/UPF1 GO:0010468 regulation of gene expression ARBA:ARBA00028334 KEEP_AS_NON_CORE very general (>200 descendants) 874 human/UPF1 GO:1903313 positive regulation of mRNA metabolic process ARBA:ARBA00026301 KEEP_AS_NON_CORE general (21-200) 32 human/UPF3A GO:0035145 exon-exon junction complex ARBA:ARBA00091546 ACCEPT specific (1-20) 1 human/UPF3A GO:0045727 positive regulation of translation ARBA:ARBA00084181 KEEP_AS_NON_CORE general (21-200) 28 human/UPF3B GO:0035145 exon-exon junction complex ARBA:ARBA00091546 ACCEPT specific (1-20) 1 human/UPF3B GO:0045727 positive regulation of translation ARBA:ARBA00084181 KEEP_AS_NON_CORE general (21-200) 28 human/UQCRB GO:0016020 membrane ARBA:ARBA00028763 MARK_AS_OVER_ANNOTATED very general (>200 descendants) 895 TOO_GENERAL true but uninformative high-level """membrane"" is a high-level parent of the specific and better-supported term mitochondrial inner membrane (GO:0005743). It is not wrong, but it is uninformatively general given more precise annotations exist." human/UQCRC1 GO:0016020 membrane ARBA:ARBA00028763 ACCEPT very general (>200 descendants) 895 human/UQCRC1 GO:0098803 respiratory chain complex ARBA:ARBA00029130 ACCEPT specific (1-20) 8 human/UQCRC2 GO:0005739 mitochondrion ARBA:ARBA00026962 ACCEPT general (21-200) 70 human/UQCRFS1 GO:0031966 mitochondrial membrane ARBA:ARBA00026364 ACCEPT general (21-200) 36 human/UQCRFS1 GO:0045275 respiratory chain complex III ARBA:ARBA00092421 ACCEPT leaf (0) 0 human/UQCRH GO:0016020 membrane ARBA:ARBA00028763 MARK_AS_OVER_ANNOTATED very general (>200 descendants) 895 TOO_GENERAL true but uninformative uninformative "Not wrong, but uninformatively general: the specific location (GO:0005743 mitochondrial inner membrane) is well established, so the bare ""membrane"" term adds no information and should not be treated as a core localization." human/UQCRH GO:0098803 respiratory chain complex ARBA:ARBA00029130 KEEP_AS_NON_CORE specific (1-20) 8 human/UROS GO:0006785 heme B biosynthetic process ARBA:ARBA00093713 MARK_AS_OVER_ANNOTATED leaf (0) 0 TOO_GENERAL true but uninformative general Over-specific for an enzyme acting at the branch point upstream of the heme-specific sub-pathway; the general heme biosynthetic process (GO:0006783) and tetrapyrrole biosynthetic process (GO:0033014) capture its role more appropriately. human/USH1C GO:0005903 brush border ARBA:ARBA00088293 ACCEPT specific (1-20) 1 human/USH1C GO:0007605 sensory perception of sound ARBA:ARBA00033578 ACCEPT specific (1-20) 2 human/USH1C GO:0050885 neuromuscular process controlling balance ARBA:ARBA00091748 MODIFY specific (1-20) 3 NEEDS_MORE_SPECIFIC true but uninformative replacement term The underlying biology is real - loss of harmonin abolishes vestibular function - but 'neuromuscular process controlling balance' mischaracterizes the mechanism: the defect is in vestibular hair-cell sensory transduction, not in a neuromuscular process. GO:0050957 'equilibrioception' (already annotated by IMP from PMID:10973247) is the accurate term. Recommend the ARBA mapping be replaced by equilibrioception. human/USH1C GO:1904106 protein localization to microvillus ARBA:ARBA00087366 ACCEPT specific (1-20) 1 human/USH1C GO:1904970 brush border assembly ARBA:ARBA00089306 ACCEPT specific (1-20) 1 human/USH1G GO:0120025 plasma membrane bounded cell projection ARBA:ARBA00028036 MODIFY very general (>200 descendants) 303 NEEDS_MORE_SPECIFIC true but uninformative replacement term The essence (SANS acts in a plasma-membrane-bounded cell projection) is sound but the term is uninformative at this depth. Replace with the specific projections supported by direct localisation data - stereocilium and photoreceptor cell cilium - rather than retaining an ARBA grouping class. human/USH2A GO:0045494 photoreceptor cell maintenance ARBA:ARBA00085416 ACCEPT leaf (0) 0 human/USH2A GO:0060113 inner ear receptor cell differentiation ARBA:ARBA00091585 ACCEPT specific (1-20) 17 human/USP21 GO:0008234 cysteine-type peptidase activity ARBA:ARBA00027409 KEEP_AS_NON_CORE specific (1-20) 16 human/USP8 GO:0005768 endosome ARBA:ARBA00028568 ACCEPT general (21-200) 68 human/UVRAG GO:0006914 autophagy ARBA:ARBA00027757 MODIFY general (21-200) 49 NEEDS_MORE_SPECIFIC true but uninformative replacement term UVRAG regulates class III PI3K/HOPS-dependent autophagosome maturation and Beclin1-PI3KC3 autophagy signaling; the parent autophagy term loses that specificity. human/UVRAG GO:0016192 vesicle-mediated transport ARBA:ARBA00028249 MODIFY very general (>200 descendants) 232 NEEDS_MORE_SPECIFIC true but uninformative replacement term UVRAG couples PtdIns(3)P-dependent ER tethering, ATG9 transport, endosome fusion, and autophagosome maturation. More specific transport terms should be used instead of the broad parent. human/UVRAG GO:0031410 cytoplasmic vesicle ARBA:ARBA00027190 MODIFY very general (>200 descendants) 274 NEEDS_MORE_SPECIFIC true but uninformative replacement term UVRAG is better localized to autophagosome/autophagosome membrane and early/late endosome compartments relevant to PI3KC3-C2 and HOPS/SNARE trafficking. human/UVRAG GO:0036092 phosphatidylinositol-3-phosphate biosynthetic process ARBA:ARBA00090298 ACCEPT specific (1-20) 3 human/UVRAG GO:0043933 protein-containing complex organization ARBA:ARBA00026287 MODIFY very general (>200 descendants) 321 NEEDS_MORE_SPECIFIC true but uninformative replacement term UVRAG participates in specific PI3KC3-C2, HOPS/class C VPS, and SNARE assembly contexts. Generic complex organization should be replaced by the specific supported complex/process annotations. human/VAPA GO:0008017 microtubule binding ARBA:ARBA00043642 KEEP_AS_NON_CORE specific (1-20) 3 human/VAPA GO:0019076 viral release from host cell ARBA:ARBA00033551 UNDECIDED specific (1-20) 9 human/VAPA GO:0030301 cholesterol transport ARBA:ARBA00034167 ACCEPT specific (1-20) 10 human/VAPA GO:0033149 FFAT motif binding ARBA:ARBA00092743 ACCEPT leaf (0) 0 human/VAPA GO:0044828 host-mediated suppression of viral genome replication ARBA:ARBA00085585 UNDECIDED leaf (0) 0 human/VAPA GO:0044829 host-mediated activation of viral genome replication ARBA:ARBA00085584 UNDECIDED leaf (0) 0 human/VAPA GO:0090114 COPII-coated vesicle budding ARBA:ARBA00033856 ACCEPT specific (1-20) 2 human/VBP1 GO:0032991 protein-containing complex ARBA:ARBA00028902 MARK_AS_OVER_ANNOTATED very general (>200 descendants) 2083 TOO_GENERAL true but uninformative general "This is an overly general annotation. VBP1 is part of the prefoldin complex (GO:0016272), which is a child term of protein-containing complex. The more specific term is already annotated with IBA, IEA, and IDA evidence. The generic ""protein-containing complex"" adds no useful information." human/VCL GO:0016020 membrane ARBA:ARBA00028763 ACCEPT very general (>200 descendants) 895 human/VCL GO:0030016 myofibril ARBA:ARBA00028265 KEEP_AS_NON_CORE specific (1-20) 17 human/VCL GO:0044291 cell-cell contact zone ARBA:ARBA00085156 ACCEPT specific (1-20) 3 human/VEGFA GO:0002376 immune system process ARBA:ARBA00027799 MARK_AS_OVER_ANNOTATED very general (>200 descendants) 673 TOO_GENERAL true but uninformative broad "While VEGFA does have immune-related functions (macrophage recruitment, M2 polarization), the term ""immune system process"" is too broad. More specific terms like macrophage chemotaxis would be more informative." human/VEGFA GO:0008284 positive regulation of cell population proliferation ARBA:ARBA00027538 ACCEPT general (21-200) 85 human/VEGFA GO:0042056 chemoattractant activity ARBA:ARBA00086225 ACCEPT specific (1-20) 1 human/VEGFA GO:0043117 positive regulation of vascular permeability ARBA:ARBA00084395 ACCEPT specific (1-20) 3 human/VEGFA GO:0043184 vascular endothelial growth factor receptor 2 binding ARBA:ARBA00084422 ACCEPT leaf (0) 0 human/VEGFA GO:0045766 positive regulation of angiogenesis ARBA:ARBA00084376 ACCEPT specific (1-20) 3 human/VEGFA GO:0048010 vascular endothelial growth factor receptor signaling pathway ARBA:ARBA00043614 ACCEPT specific (1-20) 5 human/VPS28 GO:0016236 macroautophagy ARBA:ARBA00027245 MODIFY general (21-200) 34 NEEDS_MORE_SPECIFIC true but uninformative replacement term The direct VPS28-linked evidence concerns ESCRT-I helical assembly during phagophore/autophagosome closure, so GO:0000045 autophagosome assembly is the better term. human/VPS28 GO:0036258 multivesicular body assembly ARBA:ARBA00027035 ACCEPT leaf (0) 0 human/VPS28 GO:0039702 viral budding via host ESCRT complex ARBA:ARBA00028526 KEEP_AS_NON_CORE leaf (0) 0 human/VPS37A GO:0000813 ESCRT I complex ARBA:ARBA00026622 ACCEPT leaf (0) 0 human/VPS37A GO:0016236 macroautophagy ARBA:ARBA00027245 MODIFY general (21-200) 34 NEEDS_MORE_SPECIFIC true but uninformative replacement term VPS37A is directly required for phagophore closure/autophagosome completion, so GO:0000045 autophagosome assembly is the more precise term. human/VPS37A GO:0036258 multivesicular body assembly ARBA:ARBA00027035 ACCEPT leaf (0) 0 human/VPS37A GO:0039702 viral budding via host ESCRT complex ARBA:ARBA00028526 KEEP_AS_NON_CORE leaf (0) 0 human/VPS37B GO:0000813 ESCRT I complex ARBA:ARBA00026622 ACCEPT leaf (0) 0 human/VPS37B GO:0016236 macroautophagy ARBA:ARBA00027245 MARK_AS_OVER_ANNOTATED general (21-200) 34 TOO_GENERAL true but uninformative broad The accessible ESCRT autophagy evidence is broad or VPS37A-specific; there is not enough direct evidence to make VPS37B a phagophore-closure/autophagosome assembly factor. human/VPS37B GO:0036258 multivesicular body assembly ARBA:ARBA00027035 ACCEPT leaf (0) 0 human/VPS37B GO:0039702 viral budding via host ESCRT complex ARBA:ARBA00028526 KEEP_AS_NON_CORE leaf (0) 0 human/VPS37B GO:0048306 calcium-dependent protein binding ARBA:ARBA00043551 KEEP_AS_NON_CORE specific (1-20) 1 human/VPS37C GO:0000813 ESCRT I complex ARBA:ARBA00026622 ACCEPT leaf (0) 0 human/VPS37C GO:0016236 macroautophagy ARBA:ARBA00027245 MARK_AS_OVER_ANNOTATED general (21-200) 34 TOO_GENERAL true but uninformative broad The accessible ESCRT autophagy evidence is broad or VPS37A-specific; there is not enough direct evidence to make VPS37C a phagophore-closure/autophagosome assembly factor. human/VPS37C GO:0036258 multivesicular body assembly ARBA:ARBA00027035 ACCEPT leaf (0) 0 human/VPS37C GO:0039702 viral budding via host ESCRT complex ARBA:ARBA00028526 KEEP_AS_NON_CORE leaf (0) 0 human/VPS37C GO:0048306 calcium-dependent protein binding ARBA:ARBA00043551 KEEP_AS_NON_CORE specific (1-20) 1 human/VPS37D GO:0000813 ESCRT I complex ARBA:ARBA00026622 ACCEPT leaf (0) 0 human/VPS4A GO:0000922 spindle pole ARBA:ARBA00092938 KEEP_AS_NON_CORE specific (1-20) 5 human/VPS4A GO:0005813 centrosome ARBA:ARBA00029136 KEEP_AS_NON_CORE specific (1-20) 5 human/VPS4A GO:0006997 nucleus organization ARBA:ARBA00033484 KEEP_AS_NON_CORE general (21-200) 61 human/VPS4A GO:0007041 lysosomal transport ARBA:ARBA00033548 MODIFY general (21-200) 21 NEEDS_MORE_SPECIFIC true but uninformative replacement term A more specific late endosome-to-lysosome/MVB sorting pathway term better captures the evidence. human/VPS4A GO:0007080 mitotic metaphase chromosome alignment ARBA:ARBA00033550 MARK_AS_OVER_ANNOTATED specific (1-20) 7 INDIRECT_EFFECT overreach downstream The term overstates a downstream cell-division phenotype relative to the direct ESCRT/VPS4 mechanism. human/VPS4A GO:0010389 regulation of G2/M transition of mitotic cell cycle ARBA:ARBA00093108 MARK_AS_OVER_ANNOTATED specific (1-20) 8 UNCLASSIFIED unclassified Available evidence supports ESCRT-mediated abscission and membrane remodeling, not direct regulation of the G2/M transition. human/VPS4A GO:0039702 viral budding via host ESCRT complex ARBA:ARBA00028526 KEEP_AS_NON_CORE leaf (0) 0 human/VPS4A GO:0043162 ubiquitin-dependent protein catabolic process via the multivesicular body sorting pathway ARBA:ARBA00033490 ACCEPT specific (1-20) 1 human/VPS4A GO:0051261 protein depolymerization ARBA:ARBA00028748 MODIFY specific (1-20) 12 OTHER_TERM different term needed replacement term ESCRT III complex disassembly is the specific process supported by the VPS4A mechanism. human/VPS4A GO:0061952 midbody abscission ARBA:ARBA00029210 KEEP_AS_NON_CORE leaf (0) 0 human/VPS4A GO:0090543 Flemming body ARBA:ARBA00088279 KEEP_AS_NON_CORE leaf (0) 0 human/VPS4A GO:0090611 obsolete ubiquitin-independent protein catabolic process via the multivesicular body sorting pathway ARBA:ARBA00088020 MODIFY leaf (0) 0 OTHER_TERM different term needed replacement term Use a current MVB sorting pathway term rather than retaining an obsolete ubiquitin-independent protein catabolic process term. human/VPS4A GO:1903543 positive regulation of exosomal secretion ARBA:ARBA00089029 KEEP_AS_NON_CORE leaf (0) 0 human/VPS4B GO:0000922 spindle pole ARBA:ARBA00092938 KEEP_AS_NON_CORE specific (1-20) 5 human/VPS4B GO:0005737 cytoplasm ARBA:ARBA00026971 ACCEPT very general (>200 descendants) 1146 human/VPS4B GO:0005813 centrosome ARBA:ARBA00029136 KEEP_AS_NON_CORE specific (1-20) 5 human/VPS4B GO:0006997 nucleus organization ARBA:ARBA00033484 KEEP_AS_NON_CORE general (21-200) 61 human/VPS4B GO:0007041 lysosomal transport ARBA:ARBA00033548 MODIFY general (21-200) 21 NEEDS_MORE_SPECIFIC true but uninformative replacement term A more specific late endosome-to-lysosome/MVB sorting pathway term better captures the supported role. human/VPS4B GO:0007080 mitotic metaphase chromosome alignment ARBA:ARBA00033550 MARK_AS_OVER_ANNOTATED specific (1-20) 7 INDIRECT_EFFECT overreach phenotype Available evidence supports ESCRT-mediated abscission and centrosome/spindle phenotypes, not direct control of this specific cell-cycle regulatory process as a core function. human/VPS4B GO:0010389 regulation of G2/M transition of mitotic cell cycle ARBA:ARBA00093108 MARK_AS_OVER_ANNOTATED specific (1-20) 8 INDIRECT_EFFECT overreach phenotype Available evidence supports ESCRT-mediated abscission and centrosome/spindle phenotypes, not direct control of this specific cell-cycle regulatory process as a core function. human/VPS4B GO:0039702 viral budding via host ESCRT complex ARBA:ARBA00028526 KEEP_AS_NON_CORE leaf (0) 0 human/VPS4B GO:0043162 ubiquitin-dependent protein catabolic process via the multivesicular body sorting pathway ARBA:ARBA00033490 ACCEPT specific (1-20) 1 human/VPS4B GO:0051261 protein depolymerization ARBA:ARBA00028748 MODIFY specific (1-20) 12 OTHER_TERM different term needed replacement term ESCRT III complex disassembly is the specific process supported by VPS4B biochemical evidence. human/VPS4B GO:0061952 midbody abscission ARBA:ARBA00029210 KEEP_AS_NON_CORE leaf (0) 0 human/VPS4B GO:0090543 Flemming body ARBA:ARBA00088279 KEEP_AS_NON_CORE leaf (0) 0 human/VPS4B GO:0090611 obsolete ubiquitin-independent protein catabolic process via the multivesicular body sorting pathway ARBA:ARBA00088020 MODIFY leaf (0) 0 OTHER_TERM different term needed replacement term Use a current MVB sorting pathway term rather than retaining an obsolete ubiquitin-independent protein catabolic process term. human/VPS4B GO:1903543 positive regulation of exosomal secretion ARBA:ARBA00089029 KEEP_AS_NON_CORE leaf (0) 0 human/VTI1A GO:0005737 cytoplasm ARBA:ARBA00026971 KEEP_AS_NON_CORE very general (>200 descendants) 1146 human/VTI1A GO:0012505 endomembrane system ARBA:ARBA00028953 KEEP_AS_NON_CORE very general (>200 descendants) 357 human/VTI1A GO:0016197 endosomal transport ARBA:ARBA00028239 ACCEPT general (21-200) 26 human/VTI1A GO:0061025 membrane fusion ARBA:ARBA00028823 ACCEPT general (21-200) 42 human/VTI1A GO:0098588 bounding membrane of organelle ARBA:ARBA00027281 KEEP_AS_NON_CORE very general (>200 descendants) 201 human/VWF GO:0030168 platelet activation ARBA:ARBA00027406 KEEP_AS_NON_CORE specific (1-20) 1 human/VWF GO:0031589 cell-substrate adhesion ARBA:ARBA00026745 ACCEPT specific (1-20) 20 human/VWF GO:0033093 Weibel-Palade body ARBA:ARBA00092528 ACCEPT leaf (0) 0 human/WFS1 GO:0010468 regulation of gene expression ARBA:ARBA00028334 KEEP_AS_NON_CORE very general (>200 descendants) 874 human/WFS1 GO:0035556 intracellular signal transduction ARBA:ARBA00026887 MARK_AS_OVER_ANNOTATED general (21-200) 195 TOO_GENERAL true but uninformative general This term is too general. WFS1's role in signaling is specifically in negative regulation of ER stress/UPR signaling, which is captured by more specific terms. human/WFS1 GO:1902532 negative regulation of intracellular signal transduction ARBA:ARBA00027125 KEEP_AS_NON_CORE general (21-200) 94 human/WFS1 GO:1903573 negative regulation of response to endoplasmic reticulum stress ARBA:ARBA00089122 ACCEPT specific (1-20) 7 human/WIPF1 GO:0030029 actin filament-based process ARBA:ARBA00028229 ACCEPT general (21-200) 106 human/WIPI2 GO:0006950 response to stress ARBA:ARBA00026300 KEEP_AS_NON_CORE very general (>200 descendants) 590 human/WIPI2 GO:0032266 phosphatidylinositol-3-phosphate binding ARBA:ARBA00028285 ACCEPT leaf (0) 0 human/WIPI2 GO:0034497 protein localization to phagophore assembly site ARBA:ARBA00092844 ACCEPT leaf (0) 0 human/WT1 GO:0000122 negative regulation of transcription by RNA polymerase II ARBA:ARBA00029133 ACCEPT specific (1-20) 10 human/WT1 GO:0072078 nephron tubule morphogenesis ARBA:ARBA00089551 ACCEPT general (21-200) 47 human/WT1 GO:0072359 circulatory system development ARBA:ARBA00027039 KEEP_AS_NON_CORE very general (>200 descendants) 399 human/WT1 GO:1990837 sequence-specific double-stranded DNA binding ARBA:ARBA00028376 ACCEPT general (21-200) 48 human/XBP1 GO:0030968 endoplasmic reticulum unfolded protein response ARBA:ARBA00087847 ACCEPT specific (1-20) 3 human/XBP1 GO:0043066 negative regulation of apoptotic process ARBA:ARBA00027746 KEEP_AS_NON_CORE general (21-200) 79 human/XBP1 GO:0043565 sequence-specific DNA binding ARBA:ARBA00026779 ACCEPT general (21-200) 60 human/XIAP GO:0004869 cysteine-type endopeptidase inhibitor activity ARBA:ARBA00027012 MODIFY specific (1-20) 1 OTHER_TERM different term needed replacement term XIAP BIR2/linker directly blocks caspase-3 and caspase-7 substrate grooves, and BIR3 restrains processed caspase-9. Replace the broad row with GO:0043027 to capture the direct caspase-inhibitor activity in apoptosis. human/XIAP GO:0010804 negative regulation of tumor necrosis factor-mediated signaling pathway ARBA:ARBA00084867 MARK_AS_OVER_ANNOTATED leaf (0) 0 TOO_GENERAL true but uninformative broad The direct activity is caspase inhibition and, in overexpression systems, TAK1/JNK activation. Negative regulation of the whole TNF-mediated signaling pathway is too broad. human/XIAP GO:0019899 enzyme binding ARBA:ARBA00026481 REMOVE general (21-200) 77 TOO_GENERAL true but uninformative manual TOO_GENERAL XIAP has direct caspase-inhibitor and ubiquitin-ligase molecular functions; the parent enzyme-binding term adds no mechanistic information. human/XIAP GO:0032991 protein-containing complex ARBA:ARBA00028902 REMOVE very general (>200 descendants) 2083 TOO_GENERAL true but uninformative manual TOO_GENERAL XIAP participates in several complexes, but GO:0032991 does not identify which one or what activity XIAP contributes. The protease inhibitor complex row is the useful complex annotation. human/XIAP GO:0033554 cellular response to stress ARBA:ARBA00028184 MARK_AS_OVER_ANNOTATED very general (>200 descendants) 285 UNCLASSIFIED unclassified The row is too nonspecific for a multifunctional IAP and does not identify a proximal stress-response step that XIAP executes. human/XIAP GO:0043066 negative regulation of apoptotic process ARBA:ARBA00027746 ACCEPT general (21-200) 79 human/XIAP GO:0046330 positive regulation of JNK cascade ARBA:ARBA00093162 KEEP_AS_NON_CORE leaf (0) 0 human/XRCC3 GO:0005694 chromosome ARBA:ARBA00026361 ACCEPT very general (>200 descendants) 204 human/XRCC3 GO:0006302 double-strand break repair ARBA:ARBA00027906 ACCEPT general (21-200) 28 human/YAP1 GO:0002009 morphogenesis of an epithelium ARBA:ARBA00027094 KEEP_AS_NON_CORE very general (>200 descendants) 275 human/YAP1 GO:0035329 hippo signaling ARBA:ARBA00091361 ACCEPT leaf (0) 0 human/YAP1 GO:0045599 negative regulation of fat cell differentiation ARBA:ARBA00085192 KEEP_AS_NON_CORE specific (1-20) 3 human/YAP1 GO:0045669 positive regulation of osteoblast differentiation ARBA:ARBA00084608 KEEP_AS_NON_CORE leaf (0) 0 human/YAP1 GO:0050679 positive regulation of epithelial cell proliferation ARBA:ARBA00089519 ACCEPT specific (1-20) 18 human/YAP1 GO:0072091 regulation of stem cell proliferation ARBA:ARBA00089560 KEEP_AS_NON_CORE specific (1-20) 8 human/YTHDF3 GO:0034063 cytoplasmic stress granule assembly ARBA:ARBA00090787 KEEP_AS_NON_CORE leaf (0) 0 human/YTHDF3 GO:1990247 N6-methyladenosine-containing RNA reader activity ARBA:ARBA00026824 ACCEPT leaf (0) 0 human/YWHAZ GO:0042802 identical protein binding ARBA:ARBA00027930 ACCEPT specific (1-20) 1 human/ZAP70 GO:0007159 leukocyte cell-cell adhesion ARBA:ARBA00085300 KEEP_AS_NON_CORE specific (1-20) 12 human/ZAP70 GO:0042101 T cell receptor complex ARBA:ARBA00027274 KEEP_AS_NON_CORE specific (1-20) 2 human/ZAP70 GO:0045059 positive thymic T cell selection ARBA:ARBA00093127 KEEP_AS_NON_CORE leaf (0) 0 human/ZAP70 GO:0045582 positive regulation of T cell differentiation ARBA:ARBA00028439 KEEP_AS_NON_CORE specific (1-20) 18 human/ZAP70 GO:0050900 leukocyte migration ARBA:ARBA00091273 KEEP_AS_NON_CORE general (21-200) 63 human/ZBP1 GO:0002376 immune system process ARBA:ARBA00027799 MODIFY very general (>200 descendants) 673 NEEDS_MORE_SPECIFIC true but uninformative replacement term Correct in kind but far too general for a protein whose immune role is specifically characterised. The gene already carries the informative child term; this ARBA-generated parent should be replaced by it. human/ZBP1 GO:0051607 defense response to virus ARBA:ARBA00026923 ACCEPT specific (1-20) 5 human/ZBP1 GO:0060545 positive regulation of necroptotic process ARBA:ARBA00090633 ACCEPT leaf (0) 0 human/ZFYVE26 GO:0007040 lysosome organization ARBA:ARBA00033903 ACCEPT specific (1-20) 6 mouse/Acadl GO:0005739 mitochondrion ARBA:ARBA00026962 KEEP_AS_NON_CORE general (21-200) 70 mouse/Acadl GO:0033539 fatty acid beta-oxidation using acyl-CoA dehydrogenase ARBA:ARBA00085069 ACCEPT leaf (0) 0 mouse/Agtr1a GO:0003081 regulation of systemic arterial blood pressure by renin-angiotensin ARBA:ARBA00026620 KEEP_AS_NON_CORE specific (1-20) 18 mouse/Akt1 GO:1903898 negative regulation of PERK-mediated unfolded protein response ARBA:ARBA00092204 KEEP_AS_NON_CORE leaf (0) 0 mouse/Ang2 GO:0004540 RNA nuclease activity ARBA:ARBA00027859 ACCEPT general (21-200) 41 mouse/App GO:0010604 positive regulation of macromolecule metabolic process ARBA:ARBA00026482 MARK_AS_OVER_ANNOTATED very general (>200 descendants) 467 INDIRECT_EFFECT overreach downstream The term is a broad downstream readout; APP is better captured by trafficking, adhesion/scaffold, binding, and regulated proteolysis/fragment biology terms. mouse/App GO:0012505 endomembrane system ARBA:ARBA00028953 ACCEPT very general (>200 descendants) 357 mouse/App GO:0030198 extracellular matrix organization ARBA:ARBA00033927 KEEP_AS_NON_CORE general (21-200) 23 mouse/App GO:0043005 neuron projection ARBA:ARBA00027418 ACCEPT general (21-200) 135 mouse/App GO:0051246 regulation of protein metabolic process ARBA:ARBA00028884 ACCEPT very general (>200 descendants) 442 mouse/App GO:0099503 secretory vesicle ARBA:ARBA00026625 ACCEPT general (21-200) 68 mouse/App GO:0140677 molecular function activator activity ARBA:ARBA00034589 ACCEPT general (21-200) 104 mouse/Bcl2 GO:0001541 ovarian follicle development ARBA:ARBA00090163 KEEP_AS_NON_CORE specific (1-20) 11 mouse/Bcl2 GO:0002931 response to ischemia ARBA:ARBA00089846 KEEP_AS_NON_CORE leaf (0) 0 mouse/Bcl2 GO:0008630 intrinsic apoptotic signaling pathway in response to DNA damage ARBA:ARBA00027191 ACCEPT specific (1-20) 1 mouse/Bcl2 GO:0008637 apoptotic mitochondrial changes ARBA:ARBA00049830 KEEP_AS_NON_CORE specific (1-20) 7 mouse/Bcl2 GO:0031966 mitochondrial membrane ARBA:ARBA00026364 ACCEPT general (21-200) 36 mouse/Bcl2 GO:0051384 response to glucocorticoid ARBA:ARBA00089100 KEEP_AS_NON_CORE specific (1-20) 10 mouse/Bcl2 GO:0071456 cellular response to hypoxia ARBA:ARBA00092776 KEEP_AS_NON_CORE specific (1-20) 2 mouse/Bcl2 GO:0097192 extrinsic apoptotic signaling pathway in absence of ligand ARBA:ARBA00028301 ACCEPT leaf (0) 0 mouse/Bcl2 GO:0005829 cytosol ARBA:ARBA00029243 KEEP_AS_NON_CORE general (21-200) 73 mouse/Bcl2 GO:0042542 response to hydrogen peroxide ARBA:ARBA00027382 KEEP_AS_NON_CORE specific (1-20) 4 mouse/Bcl2 GO:0043523 regulation of neuron apoptotic process ARBA:ARBA00085497 MODIFY specific (1-20) 18 NEEDS_MORE_SPECIFIC true but uninformative replacement term Bcl2 already has accepted direct mouse evidence for negative regulation of neuron apoptotic process. Narrow this broad ARBA parent to the established negative-regulation child rather than leaving the direction implicit. mouse/Brca1 GO:0070013 intracellular organelle lumen ARBA:ARBA00027917 MARK_AS_OVER_ANNOTATED very general (>200 descendants) 239 TOO_GENERAL true but uninformative broad Over-broad CC superseded by nucleus/nucleoplasm. mouse/Calm1 GO:0000086 G2/M transition of mitotic cell cycle ARBA:ARBA00090227 KEEP_AS_NON_CORE leaf (0) 0 mouse/Calm1 GO:0006897 endocytosis ARBA:ARBA00027119 KEEP_AS_NON_CORE general (21-200) 64 mouse/Calm1 GO:0051649 establishment of localization in cell ARBA:ARBA00028679 KEEP_AS_NON_CORE very general (>200 descendants) 411 mouse/Calm1 GO:0150034 distal axon ARBA:ARBA00045048 KEEP_AS_NON_CORE general (21-200) 34 mouse/Calm2 GO:0000086 G2/M transition of mitotic cell cycle ARBA:ARBA00090227 KEEP_AS_NON_CORE leaf (0) 0 mouse/Calm2 GO:0006897 endocytosis ARBA:ARBA00027119 KEEP_AS_NON_CORE general (21-200) 64 mouse/Calm2 GO:0051649 establishment of localization in cell ARBA:ARBA00028679 KEEP_AS_NON_CORE very general (>200 descendants) 411 mouse/Calm2 GO:0098793 presynapse ARBA:ARBA00028835 KEEP_AS_NON_CORE general (21-200) 52 mouse/Calm2 GO:0150034 distal axon ARBA:ARBA00045048 KEEP_AS_NON_CORE general (21-200) 34 mouse/Calm3 GO:0000086 G2/M transition of mitotic cell cycle ARBA:ARBA00090227 KEEP_AS_NON_CORE leaf (0) 0 mouse/Calm3 GO:0006897 endocytosis ARBA:ARBA00027119 KEEP_AS_NON_CORE general (21-200) 64 mouse/Calm3 GO:0051649 establishment of localization in cell ARBA:ARBA00028679 KEEP_AS_NON_CORE very general (>200 descendants) 411 mouse/Calm3 GO:0098793 presynapse ARBA:ARBA00028835 KEEP_AS_NON_CORE general (21-200) 52 mouse/Calm3 GO:0150034 distal axon ARBA:ARBA00045048 KEEP_AS_NON_CORE general (21-200) 34 mouse/Camk2a GO:0000082 G1/S transition of mitotic cell cycle ARBA:ARBA00028571 KEEP_AS_NON_CORE leaf (0) 0 mouse/Camk2a GO:0006816 calcium ion transport ARBA:ARBA00028461 KEEP_AS_NON_CORE general (21-200) 64 mouse/Camk2a GO:0043226 organelle ARBA:ARBA00029065 MARK_AS_OVER_ANNOTATED very general (>200 descendants) 1881 TOO_GENERAL true but uninformative general Term is too general and uninformative mouse/Casp8 GO:0001817 regulation of cytokine production ARBA:ARBA00028860 KEEP_AS_NON_CORE very general (>200 descendants) 259 mouse/Casp8 GO:0002682 regulation of immune system process ARBA:ARBA00027003 MARK_AS_OVER_ANNOTATED very general (>200 descendants) 1028 TOO_GENERAL true but uninformative broad Local mouse and human evidence supports cytosolic death-complex recruitment, cysteine endopeptidase activity, RIPK1/GSDMD/N4BP1 cleavage, and necroptosis restraint rather than this broad propagated context. mouse/Casp8 GO:0005886 plasma membrane ARBA:ARBA00027801 MODIFY very general (>200 descendants) 415 NEEDS_MORE_SPECIFIC true but uninformative replacement term Casp8 is recruited to death-inducing signaling complexes on the cytoplasmic face of activated receptors; the complex is the functional site, not a generic plasma-membrane location. mouse/Casp8 GO:0009967 positive regulation of signal transduction ARBA:ARBA00027202 MARK_AS_OVER_ANNOTATED very general (>200 descendants) 209 TOO_GENERAL true but uninformative broad Local mouse and human evidence supports cytosolic death-complex recruitment, cysteine endopeptidase activity, RIPK1/GSDMD/N4BP1 cleavage, and necroptosis restraint rather than this broad propagated context. mouse/Casp8 GO:0030154 cell differentiation ARBA:ARBA00027429 MARK_AS_OVER_ANNOTATED very general (>200 descendants) 1345 TOO_GENERAL true but uninformative broad Local mouse and human evidence supports cytosolic death-complex recruitment, cysteine endopeptidase activity, RIPK1/GSDMD/N4BP1 cleavage, and necroptosis restraint rather than this broad propagated context. mouse/Casp8 GO:0043009 chordate embryonic development ARBA:ARBA00027425 MARK_AS_OVER_ANNOTATED general (21-200) 101 TOO_GENERAL true but uninformative broad Local mouse and human evidence supports cytosolic death-complex recruitment, cysteine endopeptidase activity, RIPK1/GSDMD/N4BP1 cleavage, and necroptosis restraint rather than this broad propagated context. mouse/Casp8 GO:0048513 animal organ development ARBA:ARBA00029247 MARK_AS_OVER_ANNOTATED very general (>200 descendants) 1888 TOO_GENERAL true but uninformative broad Local mouse and human evidence supports cytosolic death-complex recruitment, cysteine endopeptidase activity, RIPK1/GSDMD/N4BP1 cleavage, and necroptosis restraint rather than this broad propagated context. mouse/Casp9 GO:0009411 response to UV ARBA:ARBA00028103 MARK_AS_OVER_ANNOTATED specific (1-20) 17 INDIRECT_EFFECT overreach phenotype The direct mouse UV phenotype is non-core for Casp9, and ARBA propagation of this upstream stimulus-response parent over-annotates Casp9 beyond its apoptosome-associated activation of downstream caspases. mouse/Cbl GO:1902531 regulation of intracellular signal transduction ARBA:ARBA00027126 MODIFY very general (>200 descendants) 278 OTHER_TERM different term needed replacement term Too general; a more specific negative-regulation child is available. mouse/Cbl GO:2000583 regulation of platelet-derived growth factor receptor-alpha signaling pathway ARBA:ARBA00087618 ACCEPT specific (1-20) 2 mouse/Ccne1 GO:0000723 telomere maintenance ARBA:ARBA00027335 KEEP_AS_NON_CORE specific (1-20) 18 mouse/Ccne1 GO:0006270 DNA replication initiation ARBA:ARBA00033601 ACCEPT specific (1-20) 7 mouse/Ccne1 GO:0007129 homologous chromosome pairing at meiosis ARBA:ARBA00085323 KEEP_AS_NON_CORE specific (1-20) 6 mouse/Ccne1 GO:0016538 cyclin-dependent protein serine/threonine kinase regulator activity ARBA:ARBA00027788 MODIFY specific (1-20) 2 NEEDS_MORE_SPECIFIC true but uninformative replacement term Cyclin E1 is the non-catalytic cyclin that activates CDK2; the replacement term captures this regulatory activation more specifically than the parent regulator term. mouse/Ccne1 GO:0019901 protein kinase binding ARBA:ARBA00028598 KEEP_AS_NON_CORE specific (1-20) 15 mouse/Cd48 GO:0045321 leukocyte activation ARBA:ARBA00091994 ACCEPT general (21-200) 181 mouse/Cdc42 GO:0009653 anatomical structure morphogenesis ARBA:ARBA00026583 KEEP_AS_NON_CORE very general (>200 descendants) 1501 mouse/Cdc42 GO:0051130 positive regulation of cellular component organization ARBA:ARBA00026675 KEEP_AS_NON_CORE very general (>200 descendants) 291 mouse/Cdc42 GO:0071944 cell periphery ARBA:ARBA00027443 ACCEPT very general (>200 descendants) 493 mouse/Cdk5r1 GO:0021722 superior olivary nucleus maturation ARBA:ARBA00084175 KEEP_AS_NON_CORE leaf (0) 0 mouse/Cdk5r1 GO:0021819 layer formation in cerebral cortex ARBA:ARBA00086390 KEEP_AS_NON_CORE specific (1-20) 1 mouse/Cftr GO:0097186 amelogenesis ARBA:ARBA00090096 KEEP_AS_NON_CORE specific (1-20) 1 mouse/Ctnnb1 GO:0016020 membrane ARBA:ARBA00028763 KEEP_AS_NON_CORE very general (>200 descendants) 895 mouse/Ctnnb1 GO:0045216 cell-cell junction organization ARBA:ARBA00044861 ACCEPT general (21-200) 29 mouse/Dll1 GO:0001944 vasculature development ARBA:ARBA00091285 KEEP_AS_NON_CORE general (21-200) 132 mouse/Dll1 GO:0002064 epithelial cell development ARBA:ARBA00027130 KEEP_AS_NON_CORE general (21-200) 74 mouse/Dll1 GO:0003002 regionalization ARBA:ARBA00026387 KEEP_AS_NON_CORE very general (>200 descendants) 268 mouse/Dll1 GO:0003158 endothelium development ARBA:ARBA00088444 KEEP_AS_NON_CORE general (21-200) 43 mouse/Dll1 GO:0005911 cell-cell junction ARBA:ARBA00028427 KEEP_AS_NON_CORE general (21-200) 38 mouse/Dll1 GO:0009792 embryo development ending in birth or egg hatching ARBA:ARBA00029005 KEEP_AS_NON_CORE general (21-200) 122 mouse/Dll1 GO:0030182 neuron differentiation ARBA:ARBA00027575 KEEP_AS_NON_CORE very general (>200 descendants) 323 mouse/Dll1 GO:0045165 cell fate commitment ARBA:ARBA00043601 KEEP_AS_NON_CORE very general (>200 descendants) 245 mouse/Dll1 GO:0045747 positive regulation of Notch signaling pathway ARBA:ARBA00084351 ACCEPT leaf (0) 0 mouse/Dll1 GO:0048592 eye morphogenesis ARBA:ARBA00043385 MARK_AS_OVER_ANNOTATED general (21-200) 84 TOO_GENERAL true but uninformative vague Too vague or not specifically supported for Dll1; adds no informative content. mouse/Dll1 GO:0048598 embryonic morphogenesis ARBA:ARBA00043386 KEEP_AS_NON_CORE very general (>200 descendants) 256 mouse/Dll1 GO:0048638 regulation of developmental growth ARBA:ARBA00091468 KEEP_AS_NON_CORE general (21-200) 111 mouse/Dll1 GO:0048871 multicellular organismal-level homeostasis ARBA:ARBA00090712 MARK_AS_OVER_ANNOTATED general (21-200) 93 TOO_GENERAL true but uninformative vague Too vague or not specifically supported for Dll1; adds no informative content. mouse/Dll1 GO:0051049 regulation of transport ARBA:ARBA00027251 MARK_AS_OVER_ANNOTATED very general (>200 descendants) 960 TOO_GENERAL true but uninformative vague Too vague or not specifically supported for Dll1; adds no informative content. mouse/Dll1 GO:0051093 negative regulation of developmental process ARBA:ARBA00027583 KEEP_AS_NON_CORE very general (>200 descendants) 504 mouse/Dll1 GO:0051241 negative regulation of multicellular organismal process ARBA:ARBA00033877 MARK_AS_OVER_ANNOTATED very general (>200 descendants) 560 TOO_GENERAL true but uninformative vague Too vague or not specifically supported for Dll1; adds no informative content. mouse/Dll1 GO:0060562 epithelial tube morphogenesis ARBA:ARBA00090679 KEEP_AS_NON_CORE general (21-200) 143 mouse/Dll1 GO:0061326 renal tubule development ARBA:ARBA00044406 KEEP_AS_NON_CORE general (21-200) 122 mouse/Dll3 GO:0050768 negative regulation of neurogenesis ARBA:ARBA00089677 REMOVE general (21-200) 22 WRONG_DIRECTION wrong manual WRONG_DIRECTION Rule-based transfer from activating Delta ligands; for Dll3, overexpression data point in the opposite direction (promotion of neurogenesis as a Notch antagonist) and there is no loss-of-function support. mouse/Dnaja3 GO:0002376 immune system process ARBA:ARBA00027799 KEEP_AS_NON_CORE very general (>200 descendants) 673 mouse/Dnaja3 GO:0002682 regulation of immune system process ARBA:ARBA00027003 KEEP_AS_NON_CORE very general (>200 descendants) 1028 mouse/Dnaja3 GO:0005102 signaling receptor binding ARBA:ARBA00027239 ACCEPT very general (>200 descendants) 380 mouse/Dnaja3 GO:0005634 nucleus ARBA:ARBA00026330 MODIFY very general (>200 descendants) 473 OTHER_TERM different term needed replacement term Replace the unsupported nuclear localization with the mitochondrial localization supported by the available evidence. mouse/Dnaja3 GO:0006950 response to stress ARBA:ARBA00026300 MARK_AS_OVER_ANNOTATED very general (>200 descendants) 590 TOO_GENERAL true but uninformative broad This broad stress-response IEA is inferred from DnaJ/HSP40 family context and lacks Dnaja3-specific local support as a core function. mouse/Dnaja3 GO:0007528 neuromuscular junction development ARBA:ARBA00086386 KEEP_AS_NON_CORE specific (1-20) 4 mouse/Dnaja3 GO:0019901 protein kinase binding ARBA:ARBA00028598 ACCEPT specific (1-20) 15 mouse/Dnaja3 GO:0042127 regulation of cell population proliferation ARBA:ARBA00027546 KEEP_AS_NON_CORE very general (>200 descendants) 258 mouse/Dnaja3 GO:0043069 negative regulation of programmed cell death ARBA:ARBA00027748 KEEP_AS_NON_CORE general (21-200) 89 mouse/Dnmt1 GO:0006346 DNA methylation-dependent constitutive heterochromatin formation ARBA:ARBA00086060 KEEP_AS_NON_CORE specific (1-20) 4 mouse/Dnmt1 GO:1903925 response to bisphenol A ARBA:ARBA00092492 KEEP_AS_NON_CORE specific (1-20) 1 mouse/Drd1 GO:0001975 response to amphetamine ARBA:ARBA00028220 KEEP_AS_NON_CORE specific (1-20) 1 mouse/Drd1 GO:0008306 associative learning ARBA:ARBA00091919 KEEP_AS_NON_CORE specific (1-20) 4 mouse/Drd1 GO:0042220 response to cocaine ARBA:ARBA00026543 KEEP_AS_NON_CORE specific (1-20) 2 mouse/Drd1 GO:0046960 sensitization ARBA:ARBA00084721 KEEP_AS_NON_CORE leaf (0) 0 mouse/Drd1 GO:0060292 long-term synaptic depression ARBA:ARBA00091238 KEEP_AS_NON_CORE leaf (0) 0 mouse/Drd1 GO:0120025 plasma membrane bounded cell projection ARBA:ARBA00028036 MARK_AS_OVER_ANNOTATED very general (>200 descendants) 303 INDIRECT_EFFECT overreach phenotype 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/Ednra GO:0008015 blood circulation ARBA:ARBA00029044 KEEP_AS_NON_CORE general (21-200) 169 mouse/Ednra GO:0030202 heparin proteoglycan metabolic process ARBA:ARBA00085484 MARK_AS_OVER_ANNOTATED specific (1-20) 3 INDIRECT_EFFECT overreach phenotype 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/Ednra GO:0043123 positive regulation of canonical NF-kappaB signal transduction ARBA:ARBA00026690 MARK_AS_OVER_ANNOTATED leaf (0) 0 INDIRECT_EFFECT overreach phenotype 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/Ednra GO:0055078 sodium ion homeostasis ARBA:ARBA00084789 KEEP_AS_NON_CORE specific (1-20) 2 mouse/Ednra GO:0061028 establishment of endothelial barrier ARBA:ARBA00090320 KEEP_AS_NON_CORE specific (1-20) 2 mouse/Ednra GO:0070294 renal sodium ion absorption ARBA:ARBA00091810 KEEP_AS_NON_CORE leaf (0) 0 mouse/Ednra GO:0071806 protein transmembrane transport ARBA:ARBA00028318 MARK_AS_OVER_ANNOTATED general (21-200) 33 INDIRECT_EFFECT overreach phenotype 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/Ednra GO:0072112 podocyte differentiation ARBA:ARBA00091519 KEEP_AS_NON_CORE specific (1-20) 8 mouse/Ednra GO:0097018 renal albumin absorption ARBA:ARBA00090315 KEEP_AS_NON_CORE leaf (0) 0 mouse/Egf GO:0005154 epidermal growth factor receptor binding ARBA:ARBA00085861 ACCEPT leaf (0) 0 mouse/Egf GO:0010604 positive regulation of macromolecule metabolic process ARBA:ARBA00026482 MARK_AS_OVER_ANNOTATED very general (>200 descendants) 467 TOO_GENERAL true but uninformative broad Over-broad metabolic-regulation parent. mouse/Egf GO:0048513 animal organ development ARBA:ARBA00029247 MARK_AS_OVER_ANNOTATED very general (>200 descendants) 1888 TOO_GENERAL true but uninformative broad Over-broad parent developmental term. mouse/Egf GO:0048731 system development ARBA:ARBA00027702 MARK_AS_OVER_ANNOTATED very general (>200 descendants) 2438 TOO_GENERAL true but uninformative broad Over-broad developmental grouping term. mouse/Egf GO:0051049 regulation of transport ARBA:ARBA00027251 MARK_AS_OVER_ANNOTATED very general (>200 descendants) 960 TOO_GENERAL true but uninformative broad Over-broad transport-regulation parent. mouse/Egf GO:0071944 cell periphery ARBA:ARBA00027443 MODIFY very general (>200 descendants) 493 NEEDS_MORE_SPECIFIC true but uninformative replacement term Too generic; specific plasma membrane known. mouse/Egf GO:0080090 regulation of primary metabolic process ARBA:ARBA00026284 MARK_AS_OVER_ANNOTATED very general (>200 descendants) 1424 TOO_GENERAL true but uninformative broad Over-broad metabolic-regulation parent. mouse/Egfr GO:0021537 telencephalon development ARBA:ARBA00084940 KEEP_AS_NON_CORE general (21-200) 80 mouse/Egfr GO:0030139 endocytic vesicle ARBA:ARBA00027489 KEEP_AS_NON_CORE general (21-200) 35 mouse/Egfr GO:0042059 negative regulation of epidermal growth factor receptor signaling pathway ARBA:ARBA00086227 KEEP_AS_NON_CORE specific (1-20) 2 mouse/Epo GO:0006950 response to stress ARBA:ARBA00026300 MARK_AS_OVER_ANNOTATED very general (>200 descendants) 590 TOO_GENERAL true but uninformative generic The stress connection is better captured by hypoxia-regulated Epo production and erythropoietic response rather than a generic response-to-stress annotation. mouse/Fbxo2 GO:0006516 glycoprotein catabolic process ARBA:ARBA00085471 ACCEPT specific (1-20) 11 mouse/Fbxo2 GO:0019005 SCF ubiquitin ligase complex ARBA:ARBA00091951 ACCEPT specific (1-20) 18 mouse/Fbxo2 GO:0031146 SCF-dependent proteasomal ubiquitin-dependent protein catabolic process ARBA:ARBA00084384 ACCEPT leaf (0) 0 mouse/Fbxo2 GO:0036503 ERAD pathway ARBA:ARBA00029018 ACCEPT specific (1-20) 3 mouse/Gapdh GO:0006094 gluconeogenesis ARBA:ARBA00084701 ACCEPT leaf (0) 0 mouse/Gas6 GO:0016477 cell migration ARBA:ARBA00028795 KEEP_AS_NON_CORE very general (>200 descendants) 257 mouse/Gas6 GO:0030154 cell differentiation ARBA:ARBA00027429 KEEP_AS_NON_CORE very general (>200 descendants) 1345 mouse/Gas6 GO:0031669 cellular response to nutrient levels ARBA:ARBA00034580 MARK_AS_OVER_ANNOTATED general (21-200) 72 UNCLASSIFIED unclassified Do not treat upstream expression or modification context as a core Gas6 biological process. mouse/Gas6 GO:0050878 regulation of body fluid levels ARBA:ARBA00029145 MARK_AS_OVER_ANNOTATED general (21-200) 71 TOO_GENERAL true but uninformative general The direct function is secreted TAM ligand signaling, not general body-fluid regulation. mouse/Ghr GO:0004903 growth hormone receptor activity ARBA:ARBA00089371 ACCEPT leaf (0) 0 mouse/Ghr GO:0060396 growth hormone receptor signaling pathway ARBA:ARBA00043314 ACCEPT specific (1-20) 1 mouse/Grb2 GO:0007265 Ras protein signal transduction ARBA:ARBA00044394 ACCEPT leaf (0) 0 mouse/Grb2 GO:0019904 protein domain specific binding ARBA:ARBA00087321 ACCEPT general (21-200) 79 mouse/Grb2 GO:0048009 insulin-like growth factor receptor signaling pathway ARBA:ARBA00090282 KEEP_AS_NON_CORE specific (1-20) 1 mouse/Hdac1 GO:0017053 transcription repressor complex ARBA:ARBA00086249 ACCEPT specific (1-20) 16 mouse/Hdac1 GO:0030178 negative regulation of Wnt signaling pathway ARBA:ARBA00027587 MODIFY specific (1-20) 7 NEEDS_MORE_SPECIFIC true but uninformative replacement term The more specific term GO:0090090 (negative regulation of canonical Wnt signaling pathway) is already annotated and is more appropriate. mouse/Hdac1 GO:0035851 Krueppel-associated box domain binding ARBA:ARBA00092305 ACCEPT leaf (0) 0 mouse/Hdac1 GO:0060789 hair follicle placode formation ARBA:ARBA00092744 KEEP_AS_NON_CORE leaf (0) 0 mouse/Hdac1 GO:0061029 eyelid development in camera-type eye ARBA:ARBA00090318 KEEP_AS_NON_CORE leaf (0) 0 mouse/Hdac1 GO:0061198 fungiform papilla formation ARBA:ARBA00090033 KEEP_AS_NON_CORE leaf (0) 0 mouse/Hdac1 GO:2001243 negative regulation of intrinsic apoptotic signaling pathway ARBA:ARBA00087892 ACCEPT specific (1-20) 13 mouse/Hes7 GO:0001227 DNA-binding transcription repressor activity, RNA polymerase II-specific ARBA:ARBA00027761 ACCEPT leaf (0) 0 mouse/Hsp90aa1 GO:0032880 regulation of protein localization ARBA:ARBA00026609 KEEP_AS_NON_CORE very general (>200 descendants) 220 mouse/Hsp90aa1 GO:0044183 protein folding chaperone ARBA:ARBA00029119 ACCEPT specific (1-20) 1 mouse/Hsp90aa1 GO:0044294 dendritic growth cone ARBA:ARBA00085158 KEEP_AS_NON_CORE specific (1-20) 1 mouse/Hsp90aa1 GO:0044295 axonal growth cone ARBA:ARBA00085157 KEEP_AS_NON_CORE specific (1-20) 1 mouse/Hspa8 GO:0006457 protein folding ARBA:ARBA00027200 ACCEPT specific (1-20) 7 mouse/Hspa8 GO:0008289 lipid binding ARBA:ARBA00027537 ACCEPT general (21-200) 94 mouse/Hspa8 GO:0043168 anion binding ARBA:ARBA00026944 MARK_AS_OVER_ANNOTATED general (21-200) 150 TOO_GENERAL true but uninformative generic Too generic. The specific activity is ATP binding (GO:0005524), which is already annotated. Anion binding does not provide additional functional information. mouse/Jak1 GO:0005737 cytoplasm ARBA:ARBA00026971 ACCEPT very general (>200 descendants) 1146 mouse/Jak1 GO:0019221 cytokine-mediated signaling pathway ARBA:ARBA00028236 KEEP_AS_NON_CORE general (21-200) 120 mouse/Jak1 GO:0098761 cellular response to interleukin-7 ARBA:ARBA00091517 KEEP_AS_NON_CORE specific (1-20) 2 mouse/Mapk1 GO:0001784 phosphotyrosine residue binding ARBA:ARBA00089668 KEEP_AS_NON_CORE leaf (0) 0 mouse/Mapk1 GO:0005769 early endosome ARBA:ARBA00028567 KEEP_AS_NON_CORE specific (1-20) 7 mouse/Mapk1 GO:0005770 late endosome ARBA:ARBA00028569 KEEP_AS_NON_CORE specific (1-20) 13 mouse/Mapk1 GO:0005794 Golgi apparatus ARBA:ARBA00028708 KEEP_AS_NON_CORE general (21-200) 48 mouse/Mapk1 GO:0031143 pseudopodium ARBA:ARBA00084382 KEEP_AS_NON_CORE specific (1-20) 1 mouse/Mapk1 GO:0032872 regulation of stress-activated MAPK cascade ARBA:ARBA00026638 MARK_AS_OVER_ANNOTATED specific (1-20) 5 TOO_GENERAL true but uninformative general The only evidence here is an ARBA machine-learning IEA and a TAS pointing at a general review; neither demonstrates mouse ERK2 regulating a stress-activated cascade. ERK-JNK/p38 crosstalk is real but context-dependent, so the claim is flagged as over-annotation rather than retained. Matches the treatment of the identical IEA and TAS rows on the ERK1 paralog Mapk3, and is consistent with the sibling GO:0051403 rows. mouse/Mapk1 GO:0042473 outer ear morphogenesis ARBA:ARBA00087231 KEEP_AS_NON_CORE specific (1-20) 2 mouse/Mapk1 GO:0043330 response to exogenous dsRNA ARBA:ARBA00043583 KEEP_AS_NON_CORE specific (1-20) 2 mouse/Mapk1 GO:0051493 regulation of cytoskeleton organization ARBA:ARBA00027391 KEEP_AS_NON_CORE general (21-200) 110 mouse/Mapk1 GO:0060020 Bergmann glial cell differentiation ARBA:ARBA00089456 KEEP_AS_NON_CORE leaf (0) 0 mouse/Mapk1 GO:0061308 cardiac neural crest cell development involved in heart development ARBA:ARBA00089518 KEEP_AS_NON_CORE specific (1-20) 3 mouse/Mapk1 GO:0071356 cellular response to tumor necrosis factor ARBA:ARBA00092549 KEEP_AS_NON_CORE specific (1-20) 2 mouse/Mapk1 GO:0072584 caveolin-mediated endocytosis ARBA:ARBA00028693 KEEP_AS_NON_CORE specific (1-20) 1 mouse/Mapk1 GO:0090170 regulation of Golgi inheritance ARBA:ARBA00028400 KEEP_AS_NON_CORE leaf (0) 0 mouse/Mapk1 GO:0150078 positive regulation of neuroinflammatory response ARBA:ARBA00085428 KEEP_AS_NON_CORE specific (1-20) 2 mouse/Mapk1 GO:2000641 regulation of early endosome to late endosome transport ARBA:ARBA00028332 KEEP_AS_NON_CORE specific (1-20) 2 mouse/Mapk1 GO:0030278 regulation of ossification ARBA:ARBA00085650 KEEP_AS_NON_CORE specific (1-20) 7 mouse/Mapk3 GO:0001784 phosphotyrosine residue binding ARBA:ARBA00089668 KEEP_AS_NON_CORE leaf (0) 0 mouse/Mapk3 GO:0005739 mitochondrion ARBA:ARBA00026962 KEEP_AS_NON_CORE general (21-200) 70 mouse/Mapk3 GO:0005769 early endosome ARBA:ARBA00028567 KEEP_AS_NON_CORE specific (1-20) 7 mouse/Mapk3 GO:0005770 late endosome ARBA:ARBA00028569 KEEP_AS_NON_CORE specific (1-20) 13 mouse/Mapk3 GO:0005794 Golgi apparatus ARBA:ARBA00028708 KEEP_AS_NON_CORE general (21-200) 48 mouse/Mapk3 GO:0005856 cytoskeleton ARBA:ARBA00029228 KEEP_AS_NON_CORE very general (>200 descendants) 300 mouse/Mapk3 GO:0031143 pseudopodium ARBA:ARBA00084382 KEEP_AS_NON_CORE specific (1-20) 1 mouse/Mapk3 GO:0032872 regulation of stress-activated MAPK cascade ARBA:ARBA00026638 MARK_AS_OVER_ANNOTATED specific (1-20) 5 UNCLASSIFIED unclassified ERK1 belongs to the classical mitogen-responsive cascade; crosstalk toward the JNK/p38 stress cascades is context-dependent and no direct mouse evidence for ERK1 regulating a stress-activated cascade is available locally, so this ARBA prediction over-reaches. mouse/Mapk3 GO:0042473 outer ear morphogenesis ARBA:ARBA00087231 KEEP_AS_NON_CORE specific (1-20) 2 mouse/Mapk3 GO:0043330 response to exogenous dsRNA ARBA:ARBA00043583 KEEP_AS_NON_CORE specific (1-20) 2 mouse/Mapk3 GO:0051493 regulation of cytoskeleton organization ARBA:ARBA00027391 KEEP_AS_NON_CORE general (21-200) 110 mouse/Mapk3 GO:0060020 Bergmann glial cell differentiation ARBA:ARBA00089456 KEEP_AS_NON_CORE leaf (0) 0 mouse/Mapk3 GO:0061308 cardiac neural crest cell development involved in heart development ARBA:ARBA00089518 KEEP_AS_NON_CORE specific (1-20) 3 mouse/Mapk3 GO:0071356 cellular response to tumor necrosis factor ARBA:ARBA00092549 KEEP_AS_NON_CORE specific (1-20) 2 mouse/Mapk3 GO:0072584 caveolin-mediated endocytosis ARBA:ARBA00028693 KEEP_AS_NON_CORE specific (1-20) 1 mouse/Mapk3 GO:0090170 regulation of Golgi inheritance ARBA:ARBA00028400 KEEP_AS_NON_CORE leaf (0) 0 mouse/Mapk3 GO:2000641 regulation of early endosome to late endosome transport ARBA:ARBA00028332 KEEP_AS_NON_CORE specific (1-20) 2 mouse/Megf10 GO:0048468 cell development ARBA:ARBA00028665 MARK_AS_OVER_ANNOTATED very general (>200 descendants) 672 TOO_GENERAL true but uninformative general Too general to be informative. mouse/Mtor GO:0019216 regulation of lipid metabolic process ARBA:ARBA00028119 KEEP_AS_NON_CORE very general (>200 descendants) 212 mouse/Mtor GO:0031346 positive regulation of cell projection organization ARBA:ARBA00086237 KEEP_AS_NON_CORE general (21-200) 43 mouse/Mtor GO:0045792 negative regulation of cell size ARBA:ARBA00084279 KEEP_AS_NON_CORE leaf (0) 0 mouse/Mtor GO:0048714 positive regulation of oligodendrocyte differentiation ARBA:ARBA00090895 KEEP_AS_NON_CORE leaf (0) 0 mouse/Mtor GO:0050795 regulation of behavior ARBA:ARBA00091595 KEEP_AS_NON_CORE general (21-200) 54 mouse/Mtor GO:0051155 positive regulation of striated muscle cell differentiation ARBA:ARBA00087718 KEEP_AS_NON_CORE specific (1-20) 8 mouse/Mtor GO:0051896 regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction ARBA:ARBA00089772 ACCEPT specific (1-20) 2 mouse/Mtor GO:0120035 regulation of plasma membrane bounded cell projection organization ARBA:ARBA00028050 KEEP_AS_NON_CORE general (21-200) 122 mouse/Nf1 GO:0005737 cytoplasm ARBA:ARBA00026971 KEEP_AS_NON_CORE very general (>200 descendants) 1146 mouse/Nf1 GO:0014037 Schwann cell differentiation ARBA:ARBA00087929 KEEP_AS_NON_CORE specific (1-20) 4 mouse/Nf1 GO:0050793 regulation of developmental process ARBA:ARBA00028689 KEEP_AS_NON_CORE very general (>200 descendants) 1542 mouse/Nf1 GO:0050807 regulation of synapse organization ARBA:ARBA00029186 KEEP_AS_NON_CORE general (21-200) 63 mouse/Nkx2-5 GO:0009888 tissue development ARBA:ARBA00028065 MARK_AS_OVER_ANNOTATED very general (>200 descendants) 1023 TOO_GENERAL true but uninformative general Too general to be informative; specific heart/spleen terms capture the role. mouse/Notch1 GO:0001525 angiogenesis ARBA:ARBA00090097 KEEP_AS_NON_CORE specific (1-20) 17 mouse/Notch1 GO:0001701 in utero embryonic development ARBA:ARBA00089616 KEEP_AS_NON_CORE general (21-200) 31 mouse/Notch1 GO:0001947 heart looping ARBA:ARBA00091286 KEEP_AS_NON_CORE leaf (0) 0 mouse/Notch1 GO:0002011 morphogenesis of an epithelial sheet ARBA:ARBA00087846 KEEP_AS_NON_CORE specific (1-20) 11 mouse/Notch1 GO:0002064 epithelial cell development ARBA:ARBA00027130 KEEP_AS_NON_CORE general (21-200) 74 mouse/Notch1 GO:0002437 inflammatory response to antigenic stimulus ARBA:ARBA00089205 KEEP_AS_NON_CORE specific (1-20) 14 mouse/Notch1 GO:0005829 cytosol ARBA:ARBA00029243 ACCEPT general (21-200) 73 mouse/Notch1 GO:0006959 humoral immune response ARBA:ARBA00026316 KEEP_AS_NON_CORE general (21-200) 25 mouse/Notch1 GO:0010001 glial cell differentiation ARBA:ARBA00091307 KEEP_AS_NON_CORE general (21-200) 52 mouse/Notch1 GO:0010718 positive regulation of epithelial to mesenchymal transition ARBA:ARBA00085207 KEEP_AS_NON_CORE specific (1-20) 6 mouse/Notch1 GO:0010720 positive regulation of cell development ARBA:ARBA00034380 KEEP_AS_NON_CORE general (21-200) 101 mouse/Notch1 GO:0012505 endomembrane system ARBA:ARBA00028953 KEEP_AS_NON_CORE very general (>200 descendants) 357 mouse/Notch1 GO:0030326 embryonic limb morphogenesis ARBA:ARBA00087370 KEEP_AS_NON_CORE specific (1-20) 6 mouse/Notch1 GO:0030513 positive regulation of BMP signaling pathway ARBA:ARBA00086892 KEEP_AS_NON_CORE leaf (0) 0 mouse/Notch1 GO:0030858 positive regulation of epithelial cell differentiation ARBA:ARBA00088239 KEEP_AS_NON_CORE specific (1-20) 18 mouse/Notch1 GO:0035850 epithelial cell differentiation involved in kidney development ARBA:ARBA00092304 KEEP_AS_NON_CORE general (21-200) 42 mouse/Notch1 GO:0042981 regulation of apoptotic process ARBA:ARBA00027086 KEEP_AS_NON_CORE very general (>200 descendants) 218 mouse/Notch1 GO:0045165 cell fate commitment ARBA:ARBA00043601 ACCEPT very general (>200 descendants) 245 mouse/Notch1 GO:0048589 developmental growth ARBA:ARBA00044390 KEEP_AS_NON_CORE general (21-200) 139 mouse/Notch1 GO:0048608 reproductive structure development ARBA:ARBA00028277 KEEP_AS_NON_CORE very general (>200 descendants) 238 mouse/Notch1 GO:0048844 artery morphogenesis ARBA:ARBA00090567 KEEP_AS_NON_CORE specific (1-20) 12 mouse/Notch1 GO:0070986 left/right axis specification ARBA:ARBA00086187 KEEP_AS_NON_CORE leaf (0) 0 mouse/Notch1 GO:0072012 glomerulus vasculature development ARBA:ARBA00089490 KEEP_AS_NON_CORE general (21-200) 27 mouse/Notch1 GO:0072080 nephron tubule development ARBA:ARBA00089540 KEEP_AS_NON_CORE general (21-200) 105 mouse/Notch1 GO:2000136 regulation of cell proliferation involved in heart morphogenesis ARBA:ARBA00088364 KEEP_AS_NON_CORE specific (1-20) 10 mouse/Pax6 GO:0001764 neuron migration ARBA:ARBA00089626 KEEP_AS_NON_CORE specific (1-20) 11 mouse/Pax6 GO:0003309 type B pancreatic cell differentiation ARBA:ARBA00088307 KEEP_AS_NON_CORE specific (1-20) 3 mouse/Pax6 GO:0005667 transcription regulator complex ARBA:ARBA00026399 KEEP_AS_NON_CORE general (21-200) 84 mouse/Pax6 GO:0009653 anatomical structure morphogenesis ARBA:ARBA00026583 MARK_AS_OVER_ANNOTATED very general (>200 descendants) 1501 TOO_GENERAL true but uninformative general ARBA machine-learning (IEA) annotation. Extremely general; more specific developmental terms exist. Over-annotation, consistent with human review. mouse/Pax6 GO:0021510 spinal cord development ARBA:ARBA00084979 KEEP_AS_NON_CORE general (21-200) 33 mouse/Pax6 GO:0021537 telencephalon development ARBA:ARBA00084940 KEEP_AS_NON_CORE general (21-200) 80 mouse/Pax6 GO:0030334 regulation of cell migration ARBA:ARBA00028900 KEEP_AS_NON_CORE very general (>200 descendants) 212 mouse/Pax6 GO:0045597 positive regulation of cell differentiation ARBA:ARBA00028476 KEEP_AS_NON_CORE very general (>200 descendants) 224 mouse/Pax6 GO:0045664 regulation of neuron differentiation ARBA:ARBA00084592 KEEP_AS_NON_CORE general (21-200) 69 mouse/Pax6 GO:0048708 astrocyte differentiation ARBA:ARBA00090893 KEEP_AS_NON_CORE specific (1-20) 8 mouse/Pax6 GO:0050767 regulation of neurogenesis ARBA:ARBA00089678 KEEP_AS_NON_CORE general (21-200) 48 mouse/Pax6 GO:0050877 nervous system process ARBA:ARBA00029146 REMOVE general (21-200) 194 TERM_MISREAD wrong manual TERM_MISREAD ARBA machine-learning (IEA) annotation. Vague physiological term with no specific support; Pax6 is a developmental TF. Removed, consistent with human review. mouse/Pax6 GO:0051656 establishment of organelle localization ARBA:ARBA00028716 MARK_AS_OVER_ANNOTATED general (21-200) 98 INDIRECT_EFFECT overreach phenotype ARBA machine-learning (IEA) annotation. Likely an echo of interkinetic nuclear migration phenotypes; far too general and indirect for a transcription factor. Over-annotation. mouse/Pax6 GO:0060041 retina development in camera-type eye ARBA:ARBA00089482 KEEP_AS_NON_CORE general (21-200) 24 mouse/Pcbd1 GO:0004505 phenylalanine 4-monooxygenase activity ARBA:ARBA00029278 REMOVE leaf (0) 0 ROLE_CONFUSION wrong manual ROLE_CONFUSION Pcbd1 has no monooxygenase chemistry: no iron centre, no pterin-dependent hydroxylase domain, and a UniProt EC assignment of 4.2.1.96 (a hydro-lyase) with the Lyase keyword. ARBA00029278 appears to have learned an association from the BH4/phenylalanine-hydroxylation context that surrounds the PCD family rather than from the family's own catalytic signature; it fires on both mouse paralogs. This is an electronic inference contradicted by the curated EC and reaction, and should be removed independently of the MGI correction requested in geneontology/go-annotation#6591. mouse/Pcbd2 GO:0004505 phenylalanine 4-monooxygenase activity ARBA:ARBA00029278 REMOVE leaf (0) 0 ROLE_CONFUSION wrong manual ROLE_CONFUSION Pcbd2 has no monooxygenase chemistry - no iron centre, no pterin-dependent hydroxylase domain - and UniProt assigns it EC 4.2.1.96 with the Lyase keyword on the strength of a direct experiment. ARBA00029278 fires on both mouse PCD paralogs, which suggests it has learned an association from the BH4/phenylalanine-hydroxylation context surrounding this family rather than from the family's own catalytic signature. An electronic inference contradicted by the curated EC and reaction; remove, and revisit the rule's condition set independently of the MGI correction requested in geneontology/go-annotation#6591. mouse/Pias1 GO:0019789 SUMO transferase activity ARBA:ARBA00027358 ACCEPT specific (1-20) 3 mouse/Pld4 GO:0005768 endosome ARBA:ARBA00028568 ACCEPT general (21-200) 68 mouse/Pld4 GO:0045145 single-stranded DNA 5'-3' DNA exonuclease activity ARBA:ARBA00092730 ACCEPT leaf (0) 0 mouse/Pld4 GO:1900015 regulation of cytokine production involved in inflammatory response ARBA:ARBA00092589 KEEP_AS_NON_CORE specific (1-20) 2 mouse/Pten GO:0009966 regulation of signal transduction ARBA:ARBA00027204 KEEP_AS_NON_CORE very general (>200 descendants) 696 mouse/Pten GO:0010604 positive regulation of macromolecule metabolic process ARBA:ARBA00026482 KEEP_AS_NON_CORE very general (>200 descendants) 467 mouse/Pten GO:0010648 negative regulation of cell communication ARBA:ARBA00026586 KEEP_AS_NON_CORE very general (>200 descendants) 305 mouse/Pten GO:0010977 negative regulation of neuron projection development ARBA:ARBA00084554 KEEP_AS_NON_CORE general (21-200) 21 mouse/Pten GO:0019899 enzyme binding ARBA:ARBA00026481 MARK_AS_OVER_ANNOTATED general (21-200) 77 TOO_GENERAL true but uninformative general Term is too general mouse/Pten GO:0023057 negative regulation of signaling ARBA:ARBA00026312 KEEP_AS_NON_CORE very general (>200 descendants) 301 mouse/Pten GO:0042995 cell projection ARBA:ARBA00027299 KEEP_AS_NON_CORE very general (>200 descendants) 347 mouse/Pten GO:0045595 regulation of cell differentiation ARBA:ARBA00028479 KEEP_AS_NON_CORE very general (>200 descendants) 697 mouse/Pten GO:0051726 regulation of cell cycle ARBA:ARBA00029144 KEEP_AS_NON_CORE very general (>200 descendants) 377 mouse/Pten GO:0060044 negative regulation of cardiac muscle cell proliferation ARBA:ARBA00089480 KEEP_AS_NON_CORE leaf (0) 0 mouse/Rab7 GO:0005770 late endosome ARBA:ARBA00028569 ACCEPT specific (1-20) 13 mouse/Rab7 GO:0098588 bounding membrane of organelle ARBA:ARBA00027281 ACCEPT very general (>200 descendants) 201 mouse/Rbpj GO:0005667 transcription regulator complex ARBA:ARBA00026399 ACCEPT general (21-200) 84 mouse/Rbpj GO:0048513 animal organ development ARBA:ARBA00029247 KEEP_AS_NON_CORE very general (>200 descendants) 1888 mouse/Sdhaf2 GO:0010719 negative regulation of epithelial to mesenchymal transition ARBA:ARBA00085215 UNDECIDED specific (1-20) 5 mouse/Sdhaf2 GO:0090090 negative regulation of canonical Wnt signaling pathway ARBA:ARBA00027950 UNDECIDED leaf (0) 0 mouse/Sirt2 GO:0033010 paranodal junction ARBA:ARBA00093102 ACCEPT leaf (0) 0 mouse/Sirt2 GO:0043220 Schmidt-Lanterman incisure ARBA:ARBA00086560 ACCEPT leaf (0) 0 mouse/Sirt2 GO:0045599 negative regulation of fat cell differentiation ARBA:ARBA00085192 ACCEPT specific (1-20) 3 mouse/Sirt2 GO:0022011 myelination in peripheral nervous system ARBA:ARBA00091367 ACCEPT specific (1-20) 2 mouse/Sirt2 GO:0031641 regulation of myelination ARBA:ARBA00087391 ACCEPT specific (1-20) 2 mouse/Sirt2 GO:0042981 regulation of apoptotic process ARBA:ARBA00027086 KEEP_AS_NON_CORE very general (>200 descendants) 218 mouse/Slc5a1 GO:0005412 D-glucose:sodium symporter activity ARBA:ARBA00087065 ACCEPT specific (1-20) 1 mouse/Src GO:0007155 cell adhesion ARBA:ARBA00028946 KEEP_AS_NON_CORE general (21-200) 88 mouse/Src GO:0007276 gamete generation ARBA:ARBA00028211 KEEP_AS_NON_CORE general (21-200) 165 mouse/Src GO:0010628 positive regulation of gene expression ARBA:ARBA00026655 KEEP_AS_NON_CORE general (21-200) 198 mouse/Src GO:0036120 cellular response to platelet-derived growth factor stimulus ARBA:ARBA00089982 KEEP_AS_NON_CORE specific (1-20) 3 mouse/Src GO:0070301 cellular response to hydrogen peroxide ARBA:ARBA00092154 KEEP_AS_NON_CORE specific (1-20) 1 mouse/Src GO:0070374 positive regulation of ERK1 and ERK2 cascade ARBA:ARBA00085202 KEEP_AS_NON_CORE leaf (0) 0 mouse/Src GO:1903829 positive regulation of protein localization ARBA:ARBA00047251 KEEP_AS_NON_CORE general (21-200) 68 mouse/Src GO:1904385 cellular response to angiotensin ARBA:ARBA00089858 KEEP_AS_NON_CORE specific (1-20) 6 mouse/Stat1 GO:0000981 DNA-binding transcription factor activity, RNA polymerase II-specific ARBA:ARBA00029016 ACCEPT specific (1-20) 8 mouse/Stat1 GO:0005654 nucleoplasm ARBA:ARBA00026290 ACCEPT general (21-200) 65 mouse/Stat1 GO:0005829 cytosol ARBA:ARBA00029243 ACCEPT general (21-200) 73 mouse/Stat1 GO:0007259 cell surface receptor signaling pathway via JAK-STAT ARBA:ARBA00034574 ACCEPT specific (1-20) 1 mouse/Stat1 GO:0008283 cell population proliferation ARBA:ARBA00035743 KEEP_AS_NON_CORE general (21-200) 163 mouse/Stat1 GO:0042981 regulation of apoptotic process ARBA:ARBA00027086 KEEP_AS_NON_CORE very general (>200 descendants) 218 mouse/Stat1 GO:0051093 negative regulation of developmental process ARBA:ARBA00027583 KEEP_AS_NON_CORE very general (>200 descendants) 504 mouse/Stat1 GO:0051607 defense response to virus ARBA:ARBA00026923 KEEP_AS_NON_CORE specific (1-20) 5 mouse/Stat1 GO:0060333 type II interferon-mediated signaling pathway ARBA:ARBA00090813 ACCEPT specific (1-20) 1 mouse/Stat1 GO:0060337 type I interferon-mediated signaling pathway ARBA:ARBA00033815 ACCEPT specific (1-20) 1 mouse/Syk GO:0019904 protein domain specific binding ARBA:ARBA00087321 MODIFY general (21-200) 79 OTHER_TERM different term needed replacement term The relevant molecular recognition is binding of phosphorylated ITAM/phosphotyrosine motifs by tandem SH2 domains. mouse/Syk GO:0043306 positive regulation of mast cell degranulation ARBA:ARBA00086079 KEEP_AS_NON_CORE specific (1-20) 1 mouse/Syk GO:0043366 beta selection ARBA:ARBA00086189 KEEP_AS_NON_CORE leaf (0) 0 mouse/Syk GO:0046638 positive regulation of alpha-beta T cell differentiation ARBA:ARBA00091954 KEEP_AS_NON_CORE specific (1-20) 9 mouse/Syk GO:0046641 positive regulation of alpha-beta T cell proliferation ARBA:ARBA00091977 KEEP_AS_NON_CORE specific (1-20) 3 mouse/Syk GO:0050850 positive regulation of calcium-mediated signaling ARBA:ARBA00091707 ACCEPT specific (1-20) 3 mouse/Syk GO:0050851 antigen receptor-mediated signaling pathway ARBA:ARBA00091706 ACCEPT specific (1-20) 4 mouse/Tert GO:0008284 positive regulation of cell population proliferation ARBA:ARBA00027538 KEEP_AS_NON_CORE general (21-200) 85 mouse/Tlr11 GO:0051707 response to other organism ARBA:ARBA00029118 KEEP_AS_NON_CORE general (21-200) 199 mouse/Tlr12 GO:0051707 response to other organism ARBA:ARBA00029118 KEEP_AS_NON_CORE general (21-200) 199 mouse/Tnfrsf1a GO:0010468 regulation of gene expression ARBA:ARBA00028334 MARK_AS_OVER_ANNOTATED very general (>200 descendants) 874 INDIRECT_EFFECT overreach phenotype 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 GO:0043065 positive regulation of apoptotic process ARBA:ARBA00027745 MODIFY general (21-200) 68 OTHER_TERM different term needed replacement term The current term is too broad or less precise than extrinsic apoptotic signaling pathway via death domain receptors for this gene. Replace it with the death-domain receptor term to align the annotation with TNFR1 biology. mouse/Tnfrsf1a GO:0050793 regulation of developmental process ARBA:ARBA00028689 MARK_AS_OVER_ANNOTATED very general (>200 descendants) 1542 INDIRECT_EFFECT overreach phenotype 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 GO:0051241 negative regulation of multicellular organismal process ARBA:ARBA00033877 MARK_AS_OVER_ANNOTATED very general (>200 descendants) 560 INDIRECT_EFFECT overreach phenotype 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 GO:0032496 response to lipopolysaccharide ARBA:ARBA00084357 MODIFY specific (1-20) 5 NEEDS_MORE_SPECIFIC true but uninformative replacement term TNFR1 acts in TNF-dependent inflammatory signaling downstream of LPS exposure, but GO:0032496 is broader than the cellular LPS-response term already supported for mouse Tnfrsf1a. Replace it with GO:0071222 and retain that LPS response as non-core relative to direct TNF receptor activity. mouse/Tnfrsf1a GO:0071396 cellular response to lipid ARBA:ARBA00027803 MODIFY general (21-200) 91 NEEDS_MORE_SPECIFIC true but uninformative replacement term GO places GO:0071222 cellular response to lipopolysaccharide under GO:0071396 cellular response to lipid. Tnfrsf1a evidence supports TNFR1-dependent inflammatory brain responses after LPS challenge, so the generic lipid-response parent should be narrowed to the LPS child and retained as non-core relative to direct TNF receptor activity. mouse/Trp53 GO:0006979 response to oxidative stress ARBA:ARBA00026273 KEEP_AS_NON_CORE general (21-200) 42 mouse/Trp53 GO:0009410 response to xenobiotic stimulus ARBA:ARBA00092608 KEEP_AS_NON_CORE general (21-200) 74 mouse/Trp53 GO:0009411 response to UV ARBA:ARBA00028103 KEEP_AS_NON_CORE specific (1-20) 17 mouse/Trp53 GO:0010165 response to X-ray ARBA:ARBA00090977 KEEP_AS_NON_CORE specific (1-20) 1 mouse/Trp53 GO:0048468 cell development ARBA:ARBA00028665 KEEP_AS_NON_CORE very general (>200 descendants) 672 mouse/Trp53 GO:0051053 negative regulation of DNA metabolic process ARBA:ARBA00088036 KEEP_AS_NON_CORE general (21-200) 61 mouse/Trp53 GO:0097190 apoptotic signaling pathway ARBA:ARBA00028296 ACCEPT general (21-200) 28 mouse/Trp53 GO:0097371 MDM2/MDM4 family protein binding ARBA:ARBA00089561 KEEP_AS_NON_CORE leaf (0) 0 mouse/Trp53 GO:2001242 regulation of intrinsic apoptotic signaling pathway ARBA:ARBA00087888 ACCEPT general (21-200) 38 mouse/Txn1 GO:0019725 cellular homeostasis ARBA:ARBA00027105 MODIFY general (21-200) 125 NEEDS_MORE_SPECIFIC true but uninformative replacement term While Trx1 does contribute to cellular homeostasis, the more specific and accurate term is GO:0045454 (cell redox homeostasis), which precisely describes the function of the thioredoxin system. rat/Akt1 GO:0005080 protein kinase C binding ARBA:ARBA00086180 KEEP_AS_NON_CORE leaf (0) 0 rat/Akt1 GO:0010765 positive regulation of sodium ion transport ARBA:ARBA00085241 KEEP_AS_NON_CORE specific (1-20) 7 rat/Akt1 GO:0032869 cellular response to insulin stimulus ARBA:ARBA00085489 KEEP_AS_NON_CORE specific (1-20) 3 rat/Aldh1l1 GO:0004030 aldehyde dehydrogenase [NAD(P)+] activity ARBA:ARBA00028733 KEEP_AS_NON_CORE general (21-200) 54 rat/Aprt GO:1901363 heterocyclic compound binding ARBA:ARBA00027813 MODIFY general (21-200) 114 NEEDS_MORE_SPECIFIC true but uninformative replacement term heterocyclic compound binding is too broad or imprecise for Aprt; replace with the more specific supported term(s): GO:0002055 adenine binding; GO:0016208 AMP binding. rat/Araf GO:0004709 MAP kinase kinase kinase activity ARBA:ARBA00049851 ACCEPT specific (1-20) 1 rat/Casp3 GO:0007413 axonal fasciculation ARBA:ARBA00084186 MARK_AS_OVER_ANNOTATED specific (1-20) 2 INDIRECT_EFFECT overreach phenotype The rule generalises a neuronal caspase phenotype into a term whose definition (collection of axons into a fascicle) does not match the experiments. Kept only as a flagged over-annotation rather than removed, and aligned with the IMP row for the same term. rat/Casp3 GO:0010212 response to ionizing radiation ARBA:ARBA00090590 MARK_AS_OVER_ANNOTATED specific (1-20) 5 TOO_GENERAL true but uninformative already captured Stimulus-response terms of this kind describe the upstream trigger rather than a caspase-3 function; the informative content is already captured by the apoptotic-execution terms. Flagged as over-annotation rather than removed, consistent with the IEP row for response to X-ray. rat/Casp3 GO:0048513 animal organ development ARBA:ARBA00029247 MARK_AS_OVER_ANNOTATED very general (>200 descendants) 1888 TOO_GENERAL true but uninformative general Too general to be informative. Caspase-3 does contribute to several developmental programmes, but those are already captured by specific non-core terms (heart development, anterior neural tube closure, keratinocyte/erythrocyte differentiation). rat/Cd48 GO:0045321 leukocyte activation ARBA:ARBA00091994 ACCEPT general (21-200) 181 rat/Ces2c GO:0052689 carboxylic ester hydrolase activity ARBA:ARBA00028109 MODIFY general (21-200) 122 NEEDS_MORE_SPECIFIC true but uninformative replacement term The annotation is directionally related to Ces2c but is too broad; the specific catalytic activity is more informative. rat/Cfd GO:0004175 endopeptidase activity ARBA:ARBA00028131 MODIFY specific (1-20) 17 NEEDS_MORE_SPECIFIC true but uninformative replacement term endopeptidase activity is too broad or imprecise for Cfd; replace with the more specific supported term(s): GO:0004252 serine-type endopeptidase activity. rat/Ckmt2 GO:0007519 skeletal muscle tissue development ARBA:ARBA00086337 MARK_AS_OVER_ANNOTATED specific (1-20) 13 UNCLASSIFIED unclassified This term derives from the developmental mRNA expression pattern (sMtCK mRNA is markedly upregulated postnatally in skeletal muscle, PMID:8086475), which reflects the rising metabolic demand for phosphocreatine buffering as muscle matures rather than a direct instructive role of Ckmt2 in tissue development. rat/Crot GO:0015908 fatty acid transport ARBA:ARBA00043302 MODIFY general (21-200) 29 NEEDS_MORE_SPECIFIC true but uninformative replacement term fatty acid transport is directionally related to Crot but should be replaced by the more specific term(s): medium-chain fatty acid transport. rat/Cyb5r3 GO:0004128 cytochrome-b5 reductase activity, acting on NAD(P)H ARBA:ARBA00027922 ACCEPT specific (1-20) 2 rat/Egfr GO:0005006 epidermal growth factor receptor activity ARBA:ARBA00086054 ACCEPT leaf (0) 0 rat/Egfr GO:0005634 nucleus ARBA:ARBA00026330 KEEP_AS_NON_CORE very general (>200 descendants) 473 rat/Egfr GO:0009986 cell surface ARBA:ARBA00027349 KEEP_AS_NON_CORE specific (1-20) 14 rat/Egfr GO:0016323 basolateral plasma membrane ARBA:ARBA00086715 KEEP_AS_NON_CORE leaf (0) 0 rat/Egfr GO:0021537 telencephalon development ARBA:ARBA00084940 KEEP_AS_NON_CORE general (21-200) 80 rat/Egfr GO:0030139 endocytic vesicle ARBA:ARBA00027489 KEEP_AS_NON_CORE general (21-200) 35 rat/Egfr GO:0038134 ERBB2-EGFR signaling pathway ARBA:ARBA00087731 KEEP_AS_NON_CORE leaf (0) 0 rat/Egfr GO:0042059 negative regulation of epidermal growth factor receptor signaling pathway ARBA:ARBA00086227 KEEP_AS_NON_CORE specific (1-20) 2 rat/Egfr GO:0048471 perinuclear region of cytoplasm ARBA:ARBA00091589 KEEP_AS_NON_CORE specific (1-20) 7 rat/Egfr GO:0050679 positive regulation of epithelial cell proliferation ARBA:ARBA00089519 KEEP_AS_NON_CORE specific (1-20) 18 rat/Elovl7 GO:0008610 lipid biosynthetic process ARBA:ARBA00027236 KEEP_AS_NON_CORE very general (>200 descendants) 258 rat/Gstt1 GO:0004602 glutathione peroxidase activity ARBA:ARBA00088290 ACCEPT leaf (0) 0 rat/Gstt1 GO:0006749 glutathione metabolic process ARBA:ARBA00027824 ACCEPT specific (1-20) 4 rat/Gstt1 GO:0009751 response to salicylic acid ARBA:ARBA00028903 MARK_AS_OVER_ANNOTATED specific (1-20) 4 UNCLASSIFIED unclassified The salicylic-acid annotation reflects source-pipeline stimulus-response provenance for Gstt1 rather than a direct glutathione transferase, dehalogenase, or alkylhalidase reaction. rat/Hspa5 GO:0034976 response to endoplasmic reticulum stress ARBA:ARBA00027479 ACCEPT general (21-200) 23 rat/Hspa5 GO:0051787 misfolded protein binding ARBA:ARBA00089965 ACCEPT leaf (0) 0 rat/Hspa8 GO:0001916 positive regulation of T cell mediated cytotoxicity ARBA:ARBA00091259 KEEP_AS_NON_CORE specific (1-20) 3 rat/Hspa8 GO:0008289 lipid binding ARBA:ARBA00027537 KEEP_AS_NON_CORE general (21-200) 94 rat/Hspa8 GO:0043066 negative regulation of apoptotic process ARBA:ARBA00027746 KEEP_AS_NON_CORE general (21-200) 79 rat/Hspa8 GO:0043168 anion binding ARBA:ARBA00026944 KEEP_AS_NON_CORE general (21-200) 150 rat/Ldhb GO:0019674 NAD+ metabolic process ARBA:ARBA00034606 KEEP_AS_NON_CORE specific (1-20) 8 rat/Ldhb GO:0051287 NAD binding ARBA:ARBA00028799 KEEP_AS_NON_CORE specific (1-20) 2 rat/Lss GO:0006695 cholesterol biosynthetic process ARBA:ARBA00087369 ACCEPT leaf (0) 0 rat/Mapk1 GO:0005654 nucleoplasm ARBA:ARBA00026290 ACCEPT general (21-200) 65 rat/Mapk1 GO:0005769 early endosome ARBA:ARBA00028567 KEEP_AS_NON_CORE specific (1-20) 7 rat/Mapk1 GO:0005770 late endosome ARBA:ARBA00028569 KEEP_AS_NON_CORE specific (1-20) 13 rat/Mapk1 GO:0005794 Golgi apparatus ARBA:ARBA00028708 KEEP_AS_NON_CORE general (21-200) 48 rat/Mapk1 GO:0032872 regulation of stress-activated MAPK cascade ARBA:ARBA00026638 KEEP_AS_NON_CORE specific (1-20) 5 rat/Mapk1 GO:0035094 response to nicotine ARBA:ARBA00089505 KEEP_AS_NON_CORE specific (1-20) 2 rat/Mapk1 GO:0045727 positive regulation of translation ARBA:ARBA00084181 KEEP_AS_NON_CORE general (21-200) 28 rat/Mapk1 GO:0046697 decidualization ARBA:ARBA00092194 KEEP_AS_NON_CORE leaf (0) 0 rat/Mapk1 GO:0051493 regulation of cytoskeleton organization ARBA:ARBA00027391 KEEP_AS_NON_CORE general (21-200) 110 rat/Mapk1 GO:0070371 ERK1 and ERK2 cascade ARBA:ARBA00085205 ACCEPT leaf (0) 0 rat/Mapk1 GO:0071375 cellular response to peptide hormone stimulus ARBA:ARBA00043567 KEEP_AS_NON_CORE general (21-200) 28 rat/Mapk1 GO:0071396 cellular response to lipid ARBA:ARBA00027803 KEEP_AS_NON_CORE general (21-200) 91 rat/Mapk1 GO:0072584 caveolin-mediated endocytosis ARBA:ARBA00028693 KEEP_AS_NON_CORE specific (1-20) 1 rat/Mapk1 GO:0090170 regulation of Golgi inheritance ARBA:ARBA00028400 KEEP_AS_NON_CORE leaf (0) 0 rat/Mapk1 GO:2000641 regulation of early endosome to late endosome transport ARBA:ARBA00028332 KEEP_AS_NON_CORE specific (1-20) 2 rat/Nat8l GO:0005739 mitochondrion ARBA:ARBA00026962 KEEP_AS_NON_CORE general (21-200) 70 rat/Oaz1 GO:0045732 positive regulation of protein catabolic process ARBA:ARBA00026548 ACCEPT specific (1-20) 13 rat/Oaz1 GO:1902268 negative regulation of polyamine transmembrane transport ARBA:ARBA00089136 ACCEPT leaf (0) 0 rat/Pgp GO:0006114 glycerol biosynthetic process ARBA:ARBA00084233 ACCEPT leaf (0) 0 rat/Pgp GO:0006650 glycerophospholipid metabolic process ARBA:ARBA00028631 KEEP_AS_NON_CORE general (21-200) 58 rat/Prkaa2 GO:0031000 response to caffeine ARBA:ARBA00084610 KEEP_AS_NON_CORE specific (1-20) 1 rat/Prkaa2 GO:0045821 positive regulation of glycolytic process ARBA:ARBA00086348 ACCEPT specific (1-20) 1 rat/Prkaa2 GO:0055089 fatty acid homeostasis ARBA:ARBA00084799 ACCEPT leaf (0) 0 rat/Prkaa2 GO:0071277 cellular response to calcium ion ARBA:ARBA00092869 KEEP_AS_NON_CORE specific (1-20) 1 rat/Prkaa2 GO:0071333 cellular response to glucose stimulus ARBA:ARBA00093092 ACCEPT specific (1-20) 3 rat/Prkaa2 GO:0097009 energy homeostasis ARBA:ARBA00090302 ACCEPT specific (1-20) 4 rat/Prkaa2 GO:0030424 axon ARBA:ARBA00028032 KEEP_AS_NON_CORE general (21-200) 59 rat/Prkaa2 GO:0030425 dendrite ARBA:ARBA00028031 KEEP_AS_NON_CORE general (21-200) 37 rat/Prkaa2 GO:0031588 nucleotide-activated protein kinase complex ARBA:ARBA00085670 ACCEPT leaf (0) 0 rat/Prkaa2 GO:0043025 neuronal cell body ARBA:ARBA00027467 KEEP_AS_NON_CORE specific (1-20) 5 rat/Qdpr GO:0042558 pteridine-containing compound metabolic process ARBA:ARBA00027196 ACCEPT general (21-200) 37 rat/Slc13a2 GO:0015370 solute:sodium symporter activity ARBA:ARBA00034186 MODIFY general (21-200) 55 NEEDS_MORE_SPECIFIC true but uninformative replacement term The generic transporter or transport term should be replaced with the specific sodium:dicarboxylate symporter activity or substrate-specific dicarboxylate transport processes. rat/Slc5a1 GO:0008324 monoatomic cation transmembrane transporter activity ARBA:ARBA00026578 MARK_AS_OVER_ANNOTATED very general (>200 descendants) 328 UNCLASSIFIED unclassified Misleading annotation. While SGLT1 translocates Na+ ions, it is primarily a sugar transporter that uses the Na+ gradient as driving force. The sodium transport is coupled to/incidental to the primary glucose transport function. rat/Sqle GO:0008203 cholesterol metabolic process ARBA:ARBA00034389 ACCEPT specific (1-20) 3 rat/Sstr5 GO:0071385 cellular response to glucocorticoid stimulus ARBA:ARBA00092516 ACCEPT specific (1-20) 4 rat/Tp53 GO:0006979 response to oxidative stress ARBA:ARBA00026273 KEEP_AS_NON_CORE general (21-200) 42 rat/Tp53 GO:0009410 response to xenobiotic stimulus ARBA:ARBA00092608 KEEP_AS_NON_CORE general (21-200) 74 rat/Tp53 GO:0009411 response to UV ARBA:ARBA00028103 KEEP_AS_NON_CORE specific (1-20) 17 rat/Tp53 GO:0010165 response to X-ray ARBA:ARBA00090977 KEEP_AS_NON_CORE specific (1-20) 1 rat/Tp53 GO:0031625 ubiquitin protein ligase binding ARBA:ARBA00028807 KEEP_AS_NON_CORE leaf (0) 0 rat/Tp53 GO:0051053 negative regulation of DNA metabolic process ARBA:ARBA00088036 MARK_AS_OVER_ANNOTATED general (21-200) 61 TOO_GENERAL true but uninformative generic Overly generic ARBA-derived term; more specific checkpoint terms preferred. rat/Tp53 GO:0071456 cellular response to hypoxia ARBA:ARBA00092776 KEEP_AS_NON_CORE specific (1-20) 2 rat/Tp53 GO:0097190 apoptotic signaling pathway ARBA:ARBA00028296 KEEP_AS_NON_CORE general (21-200) 28 rat/Tp53 GO:0097371 MDM2/MDM4 family protein binding ARBA:ARBA00089561 ACCEPT leaf (0) 0 rat/Tp53 GO:2001242 regulation of intrinsic apoptotic signaling pathway ARBA:ARBA00087888 KEEP_AS_NON_CORE general (21-200) 38 rat/Uggt1 GO:1901135 carbohydrate derivative metabolic process ARBA:ARBA00026297 KEEP_AS_NON_CORE very general (>200 descendants) 637 worm/F44E5.4 GO:0005788 endoplasmic reticulum lumen ARBA:ARBA00028691 REMOVE specific (1-20) 9 WRONG_PARALOG wrong manual WRONG_PARALOG F44E5.4/F44E5.5 has no N-terminal signal peptide and no KDEL/HDEL retrieval signal; it ends in the cytosolic EEVD motif. The ER-lumenal HSP70s of C. elegans are the BiP orthologues HSP-3 and HSP-4. The ARBA rule appears to have been triggered by generic HSP70 family membership and mislocalizes this cytosolic paralogue. worm/F44E5.4 GO:0006950 response to stress ARBA:ARBA00026300 ACCEPT very general (>200 descendants) 590 worm/aak-2 GO:0004679 AMP-activated protein kinase activity ARBA:ARBA00027028 ACCEPT leaf (0) 0 worm/aak-2 GO:0005737 cytoplasm ARBA:ARBA00026971 ACCEPT very general (>200 descendants) 1146 worm/aak-2 GO:0043050 nematode pharyngeal pumping ARBA:ARBA00084835 KEEP_AS_NON_CORE leaf (0) 0 worm/aak-2 GO:0120025 plasma membrane bounded cell projection ARBA:ARBA00028036 MODIFY very general (>200 descendants) 303 NEEDS_MORE_SPECIFIC true but uninformative replacement term This annotation is too general. The experimental evidence (PMID:18408008) specifically shows localization to axons (GO:0030424), which is a more specific child term. worm/age-1 GO:0160108 animal gross anatomical part developmental process ARBA:ARBA00098139 MARK_AS_OVER_ANNOTATED very general (>200 descendants) 3010 TOO_GENERAL true but uninformative Vague Vague machine-learned term with no specific supporting evidence for AGE-1 in gross anatomical development; developmental roles of AGE-1 are better captured by dauer and embryo development terms. worm/akt-1 GO:0005547 phosphatidylinositol-3,4,5-trisphosphate binding ARBA:ARBA00086911 ACCEPT leaf (0) 0 worm/akt-1 GO:0005886 plasma membrane ARBA:ARBA00027801 ACCEPT very general (>200 descendants) 415 worm/akt-1 GO:0008286 insulin receptor signaling pathway ARBA:ARBA00092359 ACCEPT specific (1-20) 1 worm/akt-1 GO:0008340 determination of adult lifespan ARBA:ARBA00026742 ACCEPT leaf (0) 0 worm/akt-1 GO:0008582 regulation of synaptic assembly at neuromuscular junction ARBA:ARBA00085089 KEEP_AS_NON_CORE specific (1-20) 3 worm/akt-1 GO:0010468 regulation of gene expression ARBA:ARBA00028334 KEEP_AS_NON_CORE very general (>200 descendants) 874 worm/akt-1 GO:0033554 cellular response to stress ARBA:ARBA00028184 KEEP_AS_NON_CORE very general (>200 descendants) 285 worm/akt-1 GO:0035556 intracellular signal transduction ARBA:ARBA00026887 ACCEPT general (21-200) 195 worm/akt-1 GO:0043025 neuronal cell body ARBA:ARBA00027467 ACCEPT specific (1-20) 5 worm/akt-1 GO:1902911 protein kinase complex ARBA:ARBA00026740 ACCEPT general (21-200) 55 worm/akt-2 GO:0005547 phosphatidylinositol-3,4,5-trisphosphate binding ARBA:ARBA00086911 ACCEPT leaf (0) 0 worm/akt-2 GO:0008286 insulin receptor signaling pathway ARBA:ARBA00092359 ACCEPT specific (1-20) 1 worm/akt-2 GO:0008340 determination of adult lifespan ARBA:ARBA00026742 KEEP_AS_NON_CORE leaf (0) 0 worm/akt-2 GO:0008582 regulation of synaptic assembly at neuromuscular junction ARBA:ARBA00085089 KEEP_AS_NON_CORE specific (1-20) 3 worm/akt-2 GO:0010468 regulation of gene expression ARBA:ARBA00028334 KEEP_AS_NON_CORE very general (>200 descendants) 874 worm/akt-2 GO:1902911 protein kinase complex ARBA:ARBA00026740 ACCEPT general (21-200) 55 worm/alx-1 GO:0005737 cytoplasm ARBA:ARBA00026971 MARK_AS_OVER_ANNOTATED very general (>200 descendants) 1146 TOO_GENERAL true but uninformative general "While technically correct, this IEA annotation to ""cytoplasm"" is too general to be informative. The more specific localizations (recycling endosome, MVB, basolateral plasma membrane) already captured by IDA annotations provide much more useful information about where ALX-1 functions." worm/anc-1 GO:0005737 cytoplasm ARBA:ARBA00026971 ACCEPT very general (>200 descendants) 1146 worm/anc-1 GO:0006997 nucleus organization ARBA:ARBA00033484 KEEP_AS_NON_CORE general (21-200) 61 worm/anc-1 GO:0007097 nuclear migration ARBA:ARBA00026920 KEEP_AS_NON_CORE specific (1-20) 18 worm/apb-1 GO:0005737 cytoplasm ARBA:ARBA00026971 ACCEPT very general (>200 descendants) 1146 worm/aps-2 GO:0012505 endomembrane system ARBA:ARBA00028953 ACCEPT very general (>200 descendants) 357 worm/aps-2 GO:0030659 cytoplasmic vesicle membrane ARBA:ARBA00026540 ACCEPT general (21-200) 107 worm/aps-2 GO:0098588 bounding membrane of organelle ARBA:ARBA00027281 MARK_AS_OVER_ANNOTATED very general (>200 descendants) 201 TOO_GENERAL true but uninformative uninformative Not wrong for the vesicle membrane but an uninformative generalisation of the cytoplasmic vesicle membrane mapping that adds no biological content. worm/aps-2 GO:0098797 plasma membrane protein complex ARBA:ARBA00028841 ACCEPT very general (>200 descendants) 309 worm/apx-1 GO:0030154 cell differentiation ARBA:ARBA00027429 ACCEPT very general (>200 descendants) 1345 worm/apx-1 GO:0051239 regulation of multicellular organismal process ARBA:ARBA00028859 KEEP_AS_NON_CORE very general (>200 descendants) 1807 worm/atg-16.2 GO:0035973 aggrephagy ARBA:ARBA00091938 ACCEPT leaf (0) 0 worm/atg-5 GO:0007033 vacuole organization ARBA:ARBA00033898 MODIFY general (21-200) 29 NEEDS_MORE_SPECIFIC true but uninformative replacement term Vacuole organization is an ancestor of autophagosome assembly (via autophagosome organization); it is true but far too general. Replace with the specific process. worm/atg-5 GO:0016236 macroautophagy ARBA:ARBA00027245 ACCEPT general (21-200) 34 worm/car-1 GO:0005737 cytoplasm ARBA:ARBA00026971 ACCEPT very general (>200 descendants) 1146 worm/cct-3 GO:0005832 chaperonin-containing T-complex ARBA:ARBA00029273 ACCEPT leaf (0) 0 worm/cct-5 GO:0005832 chaperonin-containing T-complex ARBA:ARBA00029273 ACCEPT leaf (0) 0 worm/cct-7 GO:0005832 chaperonin-containing T-complex ARBA:ARBA00029273 ACCEPT leaf (0) 0 worm/cdc-48 GO:0005634 nucleus ARBA:ARBA00026330 ACCEPT very general (>200 descendants) 473 worm/cdc-48 GO:0005789 endoplasmic reticulum membrane ARBA:ARBA00028685 ACCEPT general (21-200) 54 worm/cdc-48 GO:0009792 embryo development ending in birth or egg hatching ARBA:ARBA00029005 KEEP_AS_NON_CORE general (21-200) 122 worm/cdc-48 GO:0010498 proteasomal protein catabolic process ARBA:ARBA00028386 ACCEPT general (21-200) 21 worm/cdc-48 GO:0017111 ribonucleoside triphosphate phosphatase activity ARBA:ARBA00027223 MODIFY specific (1-20) 10 NEEDS_MORE_SPECIFIC true but uninformative replacement term While technically correct as a parent term of ATP hydrolysis activity, this annotation is too general. CDC-48.1 is an ATPase; there is no evidence it has significant activity on other ribonucleoside triphosphates. worm/cdc-48 GO:0032880 regulation of protein localization ARBA:ARBA00026609 ACCEPT very general (>200 descendants) 220 worm/cdc-48 GO:0034976 response to endoplasmic reticulum stress ARBA:ARBA00027479 ACCEPT general (21-200) 23 worm/cdc-48 GO:0042802 identical protein binding ARBA:ARBA00027930 ACCEPT specific (1-20) 1 worm/cdc-48 GO:0098796 membrane protein complex ARBA:ARBA00028844 MARK_AS_OVER_ANNOTATED very general (>200 descendants) 543 UNCLASSIFIED unclassified While CDC-48.1 associates with the ER membrane during ERAD, it is primarily a soluble cytoplasmic/nuclear protein that transiently associates with membranes. The VCP-NPL4-UFD1 complex is the appropriate complex annotation. This annotation is misleading. worm/ced-4 GO:0005829 cytosol ARBA:ARBA00029243 ACCEPT general (21-200) 73 worm/ced-4 GO:0006915 apoptotic process ARBA:ARBA00027755 MODIFY general (21-200) 115 NEEDS_MORE_SPECIFIC true but uninformative replacement term CED-4 does not execute apoptosis directly; it mediates upstream CED-3 activation in the worm apoptosome. worm/ced-4 GO:0160108 animal gross anatomical part developmental process ARBA:ARBA00098139 MARK_AS_OVER_ANNOTATED very general (>200 descendants) 3010 INDIRECT_EFFECT overreach downstream CED-4 has direct apoptotic-signaling and caspase-activation roles; animal gross anatomical part developmental process is a downstream ARBA endpoint. worm/ced-6 GO:0043277 apoptotic cell clearance ARBA:ARBA00086522 KEEP_AS_NON_CORE specific (1-20) 7 worm/cgh-1 GO:0017148 negative regulation of translation ARBA:ARBA00027301 ACCEPT general (21-200) 37 worm/cgh-1 GO:0033962 P-body assembly ARBA:ARBA00086154 ACCEPT leaf (0) 0 worm/cgh-1 GO:0043186 P granule ARBA:ARBA00026989 ACCEPT specific (1-20) 2 worm/chc-1 GO:0005737 cytoplasm ARBA:ARBA00026971 ACCEPT very general (>200 descendants) 1146 worm/chc-1 GO:0045807 positive regulation of endocytosis ARBA:ARBA00086449 MODIFY specific (1-20) 16 OTHER_TERM different term needed replacement term The regulatory framing is wrong for a coat protein: chc-1 loss abolishes yolk uptake because the coat cannot form. The process term is clathrin-dependent endocytosis. worm/che-3 GO:0005929 cilium ARBA:ARBA00028353 ACCEPT general (21-200) 115 worm/che-3 GO:0050793 regulation of developmental process ARBA:ARBA00028689 KEEP_AS_NON_CORE very general (>200 descendants) 1542 worm/che-3 GO:0060271 cilium assembly ARBA:ARBA00027837 ACCEPT specific (1-20) 19 worm/cmd-1 GO:0072686 mitotic spindle ARBA:ARBA00033940 KEEP_AS_NON_CORE specific (1-20) 8 worm/cpx-1 GO:0030424 axon ARBA:ARBA00028032 ACCEPT general (21-200) 59 worm/cpx-1 GO:0045202 synapse ARBA:ARBA00027462 ACCEPT general (21-200) 142 worm/daf-11 GO:0009266 response to temperature stimulus ARBA:ARBA00026893 MARK_AS_OVER_ANNOTATED general (21-200) 25 INDIRECT_EFFECT overreach phenotype There is no evidence that DAF-11 participates in thermosensation; thermosensory cGMP in AFD is produced by GCY-8/GCY-18/GCY-23. The temperature dependence of daf-11 dauer phenotypes reflects the temperature sensitivity of the dauer decision itself, not a DAF-11 role in sensing temperature. worm/daf-11 GO:0009581 detection of external stimulus ARBA:ARBA00027562 KEEP_AS_NON_CORE general (21-200) 45 worm/daf-11 GO:0009582 detection of abiotic stimulus ARBA:ARBA00027563 MARK_AS_OVER_ANNOTATED general (21-200) 46 INDIRECT_EFFECT overreach downstream The only abiotic stimulus for which DAF-11 is required is light, where the detecting molecule is the LITE-1 receptor and DAF-11 acts downstream as the cyclase; phototransduction (accepted separately) captures this more accurately. DAF-11 has no role in temperature or mechanical detection. worm/daf-11 GO:0042330 taxis ARBA:ARBA00028791 KEEP_AS_NON_CORE general (21-200) 87 worm/daf-11 GO:0043005 neuron projection ARBA:ARBA00027418 KEEP_AS_NON_CORE general (21-200) 135 worm/daf-16 GO:0001228 DNA-binding transcription activator activity, RNA polymerase II-specific ARBA:ARBA00027759 ACCEPT leaf (0) 0 worm/daf-16 GO:0008286 insulin receptor signaling pathway ARBA:ARBA00092359 ACCEPT specific (1-20) 1 worm/daf-16 GO:0008340 determination of adult lifespan ARBA:ARBA00026742 ACCEPT leaf (0) 0 worm/daf-16 GO:0009896 positive regulation of catabolic process ARBA:ARBA00028093 ACCEPT general (21-200) 120 worm/daf-16 GO:0010883 regulation of lipid storage ARBA:ARBA00084945 ACCEPT specific (1-20) 8 worm/daf-16 GO:0031349 positive regulation of defense response ARBA:ARBA00028260 ACCEPT general (21-200) 156 worm/daf-16 GO:0034599 cellular response to oxidative stress ARBA:ARBA00027632 ACCEPT general (21-200) 25 worm/daf-16 GO:0040015 negative regulation of multicellular organism growth ARBA:ARBA00086733 ACCEPT leaf (0) 0 worm/daf-16 GO:0042594 response to starvation ARBA:ARBA00034570 ACCEPT general (21-200) 41 worm/daf-16 GO:0050778 positive regulation of immune response ARBA:ARBA00028646 ACCEPT very general (>200 descendants) 217 worm/daf-18 GO:0050793 regulation of developmental process ARBA:ARBA00028689 KEEP_AS_NON_CORE very general (>200 descendants) 1542 worm/dct-1 GO:0005739 mitochondrion ARBA:ARBA00026962 ACCEPT general (21-200) 70 worm/dct-1 GO:0042802 identical protein binding ARBA:ARBA00027930 MODIFY specific (1-20) 1 NEEDS_MORE_SPECIFIC true but uninformative replacement term "The annotation is correct - DCT-1 homodimerizes - but the term ""identical protein binding"" is too general. The more specific term ""protein homodimerization activity"" (GO:0042803) is already annotated with IDA evidence. This IEA should be replaced with the more specific term." worm/drp-1 GO:0005737 cytoplasm ARBA:ARBA00026971 ACCEPT very general (>200 descendants) 1146 worm/dve-1 GO:0003700 DNA-binding transcription factor activity ARBA:ARBA00028295 ACCEPT specific (1-20) 16 worm/dve-1 GO:0006357 regulation of transcription by RNA polymerase II ARBA:ARBA00028137 ACCEPT general (21-200) 56 worm/dyf-11 GO:0048513 animal organ development ARBA:ARBA00029247 MARK_AS_OVER_ANNOTATED very general (>200 descendants) 1888 TOO_GENERAL true but uninformative Vague Vague electronic annotation with no experimental support in this organism; DYF-11's role is specific to sensory cilium assembly/function. worm/dyf-11 GO:0048731 system development ARBA:ARBA00027702 MARK_AS_OVER_ANNOTATED very general (>200 descendants) 2438 TOO_GENERAL true but uninformative Vague Vague electronic annotation; DYF-11's characterized function is ciliogenesis, better captured by cilium assembly. worm/dyf-11 GO:0070507 regulation of microtubule cytoskeleton organization ARBA:ARBA00033510 MARK_AS_OVER_ANNOTATED general (21-200) 34 UNCLASSIFIED unclassified DYF-11 is a structural IFT-B subunit, not a regulator of microtubule dynamics; the microtubule-related role is axoneme assembly (cilium assembly / intraciliary transport). worm/dyf-2 GO:0008104 intracellular protein localization ARBA:ARBA00028253 MODIFY very general (>200 descendants) 356 NEEDS_MORE_SPECIFIC true but uninformative replacement term """intracellular protein localization"" is uninformatively broad. The experimental basis (loss of DYF-2 mislocalizes ciliary IFT-A/IFT-B proteins) and DYF-2's IFT-A function are better captured by ""protein localization to cilium""." worm/dyf-2 GO:0030990 intraciliary transport particle ARBA:ARBA00050083 KEEP_AS_NON_CORE specific (1-20) 2 worm/dyf-2 GO:0044782 cilium organization ARBA:ARBA00027540 KEEP_AS_NON_CORE general (21-200) 28 worm/dyf-6 GO:0120025 plasma membrane bounded cell projection ARBA:ARBA00028036 MARK_AS_OVER_ANNOTATED very general (>200 descendants) 303 TOO_GENERAL true but uninformative general Over-general electronic grouping term; its informative descendants (cilium, dendrite) are already annotated, so it adds no information. worm/dyn-1 GO:0006898 receptor-mediated endocytosis ARBA:ARBA00044584 ACCEPT general (21-200) 30 worm/dyn-1 GO:0012501 programmed cell death ARBA:ARBA00028943 MODIFY general (21-200) 147 OTHER_TERM different term needed replacement term The process DYN-1 participates in is apoptotic cell clearance (engulfment and phagosome maturation), which is the appropriate term; programmed cell death describes the dying cell's program. worm/elt-2 GO:0000976 transcription cis-regulatory region binding ARBA:ARBA00028970 ACCEPT general (21-200) 32 worm/elt-2 GO:0009888 tissue development ARBA:ARBA00028065 MODIFY very general (>200 descendants) 1023 NEEDS_MORE_SPECIFIC true but uninformative replacement term While accurate, this term is too general. ELT-2 specifically regulates endoderm/intestinal development. worm/ent-1 GO:0015858 nucleoside transport ARBA:ARBA00027644 ACCEPT general (21-200) 29 worm/ent-1 GO:0022857 transmembrane transporter activity ARBA:ARBA00028127 MODIFY very general (>200 descendants) 990 NEEDS_MORE_SPECIFIC true but uninformative replacement term While correct, this term is too general. The more specific nucleoside transmembrane transporter activity term better describes ENT-1 function. worm/fzo-1 GO:0007005 mitochondrion organization ARBA:ARBA00026723 ACCEPT general (21-200) 37 worm/gcn-2 GO:0009893 positive regulation of metabolic process ARBA:ARBA00028097 MARK_AS_OVER_ANNOTATED very general (>200 descendants) 739 TOO_GENERAL true but uninformative broad Too broad to be informative for this specific kinase. The more specific processes regulated by GCN-2 (translation, stress response) are annotated separately. worm/gcn-2 GO:0010468 regulation of gene expression ARBA:ARBA00028334 ACCEPT very general (>200 descendants) 874 worm/gcn-2 GO:0033554 cellular response to stress ARBA:ARBA00028184 ACCEPT very general (>200 descendants) 285 worm/gcn-2 GO:0051246 regulation of protein metabolic process ARBA:ARBA00028884 ACCEPT very general (>200 descendants) 442 worm/gcy-18 GO:0016048 detection of temperature stimulus ARBA:ARBA00087525 ACCEPT specific (1-20) 5 worm/gcy-18 GO:0040040 thermosensory behavior ARBA:ARBA00086785 ACCEPT leaf (0) 0 worm/gcy-18 GO:0043052 thermotaxis ARBA:ARBA00084834 ACCEPT leaf (0) 0 worm/gcy-18 GO:0044306 neuron projection terminus ARBA:ARBA00084726 ACCEPT general (21-200) 23 worm/gcy-23 GO:0016048 detection of temperature stimulus ARBA:ARBA00087525 ACCEPT specific (1-20) 5 worm/gcy-23 GO:0040040 thermosensory behavior ARBA:ARBA00086785 ACCEPT leaf (0) 0 worm/gcy-23 GO:0043052 thermotaxis ARBA:ARBA00084834 ACCEPT leaf (0) 0 worm/gcy-23 GO:0044306 neuron projection terminus ARBA:ARBA00084726 ACCEPT general (21-200) 23 worm/gcy-33 GO:0070482 response to oxygen levels ARBA:ARBA00029157 ACCEPT general (21-200) 24 worm/gcy-8 GO:0009266 response to temperature stimulus ARBA:ARBA00026893 ACCEPT general (21-200) 25 worm/gcy-8 GO:0009581 detection of external stimulus ARBA:ARBA00027562 KEEP_AS_NON_CORE general (21-200) 45 worm/gcy-8 GO:0009582 detection of abiotic stimulus ARBA:ARBA00027563 KEEP_AS_NON_CORE general (21-200) 46 worm/gcy-8 GO:0042330 taxis ARBA:ARBA00028791 KEEP_AS_NON_CORE general (21-200) 87 worm/gcy-8 GO:0043005 neuron projection ARBA:ARBA00027418 KEEP_AS_NON_CORE general (21-200) 135 worm/glh-1 GO:0008432 JUN kinase binding ARBA:ARBA00085233 ACCEPT leaf (0) 0 worm/glh-1 GO:0043186 P granule ARBA:ARBA00026989 ACCEPT specific (1-20) 2 worm/glh-1 GO:0007281 germ cell development ARBA:ARBA00028319 ACCEPT general (21-200) 112 worm/glh-1 GO:0009791 post-embryonic development ARBA:ARBA00029007 KEEP_AS_NON_CORE very general (>200 descendants) 271 worm/glh-2 GO:0007281 germ cell development ARBA:ARBA00028319 ACCEPT general (21-200) 112 worm/glh-2 GO:0008432 JUN kinase binding ARBA:ARBA00085233 ACCEPT leaf (0) 0 worm/glh-2 GO:0009791 post-embryonic development ARBA:ARBA00029007 KEEP_AS_NON_CORE very general (>200 descendants) 271 worm/glh-2 GO:0043186 P granule ARBA:ARBA00026989 ACCEPT specific (1-20) 2 worm/glh-4 GO:0008432 JUN kinase binding ARBA:ARBA00085233 ACCEPT leaf (0) 0 worm/glh-4 GO:0043186 P granule ARBA:ARBA00026989 ACCEPT specific (1-20) 2 worm/glp-1 GO:0001708 cell fate specification ARBA:ARBA00089615 ACCEPT general (21-200) 55 worm/glp-1 GO:0022611 dormancy process ARBA:ARBA00091893 KEEP_AS_NON_CORE general (21-200) 26 worm/glp-1 GO:0040024 dauer larval development ARBA:ARBA00086745 KEEP_AS_NON_CORE specific (1-20) 3 worm/glp-1 GO:0048589 developmental growth ARBA:ARBA00044390 KEEP_AS_NON_CORE general (21-200) 139 worm/glp-1 GO:0061629 RNA polymerase II-specific DNA-binding transcription factor binding ARBA:ARBA00028384 ACCEPT specific (1-20) 16 worm/glp-1 GO:0090575 RNA polymerase II transcription regulator complex ARBA:ARBA00028248 ACCEPT general (21-200) 44 worm/gst-4 GO:0005737 cytoplasm ARBA:ARBA00026971 ACCEPT very general (>200 descendants) 1146 worm/hip-1 GO:0005634 nucleus ARBA:ARBA00026330 REMOVE very general (>200 descendants) 473 WRONG_LOCATION wrong manual WRONG_LOCATION Over-propagated electronic inference that conflicts with the well-established cytosolic biology of Hip-family co-chaperones; not supported by any experimental or phylogenetic evidence for this gene. worm/hip-1 GO:0070013 intracellular organelle lumen ARBA:ARBA00027917 REMOVE very general (>200 descendants) 239 WRONG_LOCATION wrong manual WRONG_LOCATION Over-propagated electronic inference; an organelle-lumen location is not supported by any experimental or phylogenetic evidence for HIP-1 and conflicts with its cytosolic function. worm/hip-1 GO:1902494 catalytic complex ARBA:ARBA00026588 MARK_AS_OVER_ANNOTATED very general (>200 descendants) 681 TOO_GENERAL true but uninformative Uninformative Uninformative and potentially misleading: HIP-1 does not catalyze a reaction and is not a stable structural subunit of a defined catalytic complex; its interaction with Hsp70 is transient and regulatory. worm/hsp-1 GO:0009408 response to heat ARBA:ARBA00028092 ACCEPT specific (1-20) 7 worm/hsp-110 GO:0006950 response to stress ARBA:ARBA00026300 KEEP_AS_NON_CORE very general (>200 descendants) 590 worm/hsp-16.1 GO:0005737 cytoplasm ARBA:ARBA00026971 ACCEPT very general (>200 descendants) 1146 worm/hsp-16.1 GO:0009408 response to heat ARBA:ARBA00028092 ACCEPT specific (1-20) 7 worm/hsp-16.2 GO:0005737 cytoplasm ARBA:ARBA00026971 ACCEPT very general (>200 descendants) 1146 worm/hsp-16.2 GO:0009408 response to heat ARBA:ARBA00028092 ACCEPT specific (1-20) 7 worm/hsp-16.48 GO:0009408 response to heat ARBA:ARBA00028092 ACCEPT specific (1-20) 7 worm/hsp-3 GO:0030968 endoplasmic reticulum unfolded protein response ARBA:ARBA00087847 ACCEPT specific (1-20) 3 worm/hsp-4 GO:0030968 endoplasmic reticulum unfolded protein response ARBA:ARBA00087847 ACCEPT specific (1-20) 3 worm/hsp-6 GO:0006950 response to stress ARBA:ARBA00026300 KEEP_AS_NON_CORE very general (>200 descendants) 590 worm/hsp-70 GO:0005788 endoplasmic reticulum lumen ARBA:ARBA00028691 REMOVE specific (1-20) 9 WRONG_PARALOG wrong manual WRONG_PARALOG HSP-70 (C12C8.1) has no N-terminal signal peptide and no KDEL/HDEL retrieval signal; it ends in the cytosolic EEVD motif. The ER-lumenal HSP70s of C. elegans are the BiP orthologues HSP-3 and HSP-4. The ARBA rule appears to have been triggered by generic HSP70 family membership and mislocalizes this cytosolic paralogue. worm/hsp-70 GO:0006950 response to stress ARBA:ARBA00026300 ACCEPT very general (>200 descendants) 590 worm/hsp-90 GO:0101031 protein folding chaperone complex ARBA:ARBA00026483 ACCEPT specific (1-20) 7 worm/ift-81 GO:0005815 microtubule organizing center ARBA:ARBA00029135 ACCEPT general (21-200) 42 worm/ift-81 GO:0005929 cilium ARBA:ARBA00028353 ACCEPT general (21-200) 115 worm/ift-81 GO:0007018 microtubule-based movement ARBA:ARBA00033543 ACCEPT general (21-200) 84 worm/ire-1 GO:0010468 regulation of gene expression ARBA:ARBA00028334 ACCEPT very general (>200 descendants) 874 worm/ire-1 GO:0034976 response to endoplasmic reticulum stress ARBA:ARBA00027479 ACCEPT general (21-200) 23 worm/ire-1 GO:0080090 regulation of primary metabolic process ARBA:ARBA00026284 MARK_AS_OVER_ANNOTATED very general (>200 descendants) 1424 TOO_GENERAL true but uninformative broad While technically accurate as UPR affects protein and lipid metabolism, this term is too broad to be informative about IRE-1's specific function. More specific UPR-related terms are preferred. worm/jmjd-3.1 GO:0032452 histone demethylase activity ARBA:ARBA00026704 ACCEPT specific (1-20) 18 worm/kap-1 GO:0005634 nucleus ARBA:ARBA00026330 REMOVE very general (>200 descendants) 473 WRONG_LOCATION wrong manual WRONG_LOCATION No evidence places worm KAP-1 in the nucleus. KAP::GFP is seen in ciliated sensory neurons at the transition zone, along the cilium and in dendrites. The protein works as the cargo-binding subunit of a ciliary kinesin. This electronic inference has no support and goes against what is known about where KAP-1 acts. worm/klp-11 GO:0032991 protein-containing complex ARBA:ARBA00028902 MODIFY very general (>200 descendants) 2083 NEEDS_MORE_SPECIFIC true but uninformative replacement term Too general. Replace with the specific kinesin II complex to convey the actual assembly KLP-11 belongs to. worm/klp-20 GO:0032991 protein-containing complex ARBA:ARBA00028902 MARK_AS_OVER_ANNOTATED very general (>200 descendants) 2083 TOO_GENERAL true but uninformative Root Root-level complex membership from an ARBA rule. True (klp-20 is part of kinesin-II) but uninformative; the specific complex terms GO:0016939 and GO:0030993 supersede it. Over-annotated at this level of generality. worm/lag-1 GO:0000977 RNA polymerase II transcription regulatory region sequence-specific DNA binding ARBA:ARBA00028973 ACCEPT specific (1-20) 15 worm/lbp-8 GO:0005504 fatty acid binding ARBA:ARBA00086877 ACCEPT specific (1-20) 13 worm/let-23 GO:0038127 ERBB signaling pathway ARBA:ARBA00034175 MODIFY specific (1-20) 11 NEEDS_MORE_SPECIFIC true but uninformative replacement term C. elegans has a single EGFR-like receptor, LET-23, and the reviewed experimental and PAINT rows support GO:0007173 epidermal growth factor receptor signaling pathway. That term is more precise than the pan-ERBB pathway term for this nematode receptor. worm/lgg-2 GO:0006950 response to stress ARBA:ARBA00026300 ACCEPT very general (>200 descendants) 590 worm/lgg-2 GO:0016236 macroautophagy ARBA:ARBA00027245 ACCEPT general (21-200) 34 worm/lin-12 GO:0001708 cell fate specification ARBA:ARBA00089615 ACCEPT general (21-200) 55 worm/lin-12 GO:0022611 dormancy process ARBA:ARBA00091893 KEEP_AS_NON_CORE general (21-200) 26 worm/lin-12 GO:0040024 dauer larval development ARBA:ARBA00086745 KEEP_AS_NON_CORE specific (1-20) 3 worm/lin-12 GO:0042659 regulation of cell fate specification ARBA:ARBA00086800 ACCEPT general (21-200) 42 worm/lin-12 GO:0045597 positive regulation of cell differentiation ARBA:ARBA00028476 KEEP_AS_NON_CORE very general (>200 descendants) 224 worm/lin-12 GO:0048513 animal organ development ARBA:ARBA00029247 KEEP_AS_NON_CORE very general (>200 descendants) 1888 worm/lin-12 GO:0061629 RNA polymerase II-specific DNA-binding transcription factor binding ARBA:ARBA00028384 ACCEPT specific (1-20) 16 worm/lin-12 GO:1990433 CSL-Notch-Mastermind transcription factor complex ARBA:ARBA00090083 ACCEPT leaf (0) 0 worm/lis-1 GO:0006909 phagocytosis ARBA:ARBA00027650 MARK_AS_OVER_ANNOTATED specific (1-20) 15 INDIRECT_EFFECT overreach phenotype No evidence that LIS-1 acts in phagocytosis per se. The only related data are slowed engulfment of germline corpses in lis-1 and dhc-1 mutants, which is a whole-animal phenotype (engulfment is performed by sheath cells) and is annotated separately as engulfment of apoptotic cell; the generic machine-learning phagocytosis inference overstates this. worm/lis-1 GO:0007154 cell communication ARBA:ARBA00028945 REMOVE very general (>200 descendants) 1207 WRONG_PROCESS wrong manual WRONG_PROCESS Over-general machine-learning inference with no C. elegans or family evidence that LIS-1 is a component of a cell communication pathway; the neural phenotypes reflect dynein-dependent transport. worm/lis-1 GO:0023052 signaling ARBA:ARBA00026303 REMOVE very general (>200 descendants) 1141 WRONG_PROCESS wrong manual WRONG_PROCESS Over-general machine-learning inference; LIS-1 is a dynein regulator, not a signalling component, and there is no worm evidence for a signalling role. worm/lis-1 GO:0030286 dynein complex ARBA:ARBA00085634 MODIFY specific (1-20) 4 TOO_SPECIFIC overreach replacement term LIS-1 is a transiently associated dynein regulator rather than a subunit; microtubule associated complex (consistent with the human review) plus dynein complex binding represent this better. worm/lis-1 GO:0051225 spindle assembly ARBA:ARBA00089339 ACCEPT specific (1-20) 18 worm/lis-1 GO:0051299 centrosome separation ARBA:ARBA00089326 ACCEPT specific (1-20) 1 worm/lrx-1 GO:0016192 vesicle-mediated transport ARBA:ARBA00028249 REMOVE very general (>200 descendants) 232 SPURIOUS_SIGNATURE wrong manual SPURIOUS_SIGNATURE Based on false LDL receptor domain predictions; no evidence for cargo receptor function. Falcon deep research explicitly states there is no evidence base to claim lrx-1 mediates endocytosis or binds lipoprotein ligands. worm/lys-1 GO:0006950 response to stress ARBA:ARBA00026300 MARK_AS_OVER_ANNOTATED very general (>200 descendants) 590 TOO_GENERAL true but uninformative general Too general to be informative and subsumed by the specific defense response / innate immune response annotations that are experimentally supported. worm/lys-7 GO:0006950 response to stress ARBA:ARBA00026300 ACCEPT very general (>200 descendants) 590 worm/mek-2 GO:0000165 MAPK cascade ARBA:ARBA00029221 ACCEPT specific (1-20) 18 worm/mek-2 GO:0004712 protein serine/threonine/tyrosine kinase activity ARBA:ARBA00043550 MODIFY specific (1-20) 2 NEEDS_MORE_SPECIFIC true but uninformative replacement term The ARBA protein serine/threonine/tyrosine kinase call is compatible with MEK-2 chemistry, but it does not capture the physiological MAPK substrate class. The more specific MAP kinase kinase term should be used. worm/mek-2 GO:0006950 response to stress ARBA:ARBA00026300 REMOVE very general (>200 descendants) 590 TOO_GENERAL true but uninformative manual TOO_GENERAL The supported MEK-2 stress role is the existing, experimentally curated defense response to Gram-positive bacterium row. Replacing this ARBA parent with the same pathogen-specific term would duplicate that IMP annotation, so the generic parent should be removed. worm/met-2 GO:0046974 histone H3K9 methyltransferase activity ARBA:ARBA00034949 ACCEPT specific (1-20) 4 worm/mex-5 GO:0043186 P granule ARBA:ARBA00026989 ACCEPT specific (1-20) 2 worm/mex-6 GO:0043186 P granule ARBA:ARBA00026989 ACCEPT specific (1-20) 2 worm/mff-2 GO:0005737 cytoplasm ARBA:ARBA00026971 ACCEPT very general (>200 descendants) 1146 worm/mks-1 GO:0005929 cilium ARBA:ARBA00028353 MODIFY general (21-200) 115 NEEDS_MORE_SPECIFIC true but uninformative replacement term The annotation is not incorrect since the transition zone is part of the cilium, but it is too general. MKS-1 specifically localizes to the ciliary transition zone, which is a distinct subcompartment. The GO:0035869 (ciliary transition zone) term would be more informative and accurate. Additionally, the MKS complex annotation (GO:0036038) already captures the localization since the MKS complex is by definition located at the transition zone. worm/mks-5 GO:0005856 cytoskeleton ARBA:ARBA00029228 MARK_AS_OVER_ANNOTATED very general (>200 descendants) 300 TOO_GENERAL true but uninformative broad While cilia are cytoskeleton-related structures, this annotation is overly broad and uninformative. The specific localization to the ciliary transition zone (GO:0035869) is much more appropriate and experimentally validated. This IEA is based on ARBA machine learning and lacks specificity. worm/mksr-1 GO:0005929 cilium ARBA:ARBA00028353 MODIFY general (21-200) 115 NEEDS_MORE_SPECIFIC true but uninformative replacement term The generic 'cilium' location is subsumed by the specific, experimentally supported 'ciliary transition zone' localization (IDA, PMID:21422230). Replace with the more informative and accurate compartment term. worm/mksr-2 GO:0005929 cilium ARBA:ARBA00028353 MODIFY general (21-200) 115 NEEDS_MORE_SPECIFIC true but uninformative replacement term MKSR-2 specifically localizes to the ciliary transition zone, not the cilium proper. The IEA annotation is too broad. The protein is found at the base of cilia (transition zone/basal body region). worm/mom-4 GO:0004674 protein serine/threonine kinase activity ARBA:ARBA00027016 ACCEPT general (21-200) 66 worm/mpk-1 GO:0005737 cytoplasm ARBA:ARBA00026971 ACCEPT very general (>200 descendants) 1146 worm/mut-14 GO:0043186 P granule ARBA:ARBA00026989 MODIFY specific (1-20) 2 OTHER_TERM different term needed replacement term As for the IBA, MUT-14 is in Mutator foci, next to but separate from P granules. worm/odr-1 GO:0007635 chemosensory behavior ARBA:ARBA00027929 KEEP_AS_NON_CORE specific (1-20) 7 worm/odr-1 GO:0050913 sensory perception of bitter taste ARBA:ARBA00091293 KEEP_AS_NON_CORE specific (1-20) 3 worm/odr-3 GO:0006950 response to stress ARBA:ARBA00026300 MARK_AS_OVER_ANNOTATED very general (>200 descendants) 590 TOO_GENERAL true but uninformative generic ODR-3 is required for sensory avoidance behaviours (osmotic, nociceptive) mediated by ASH, which are better described by specific sensory/behavioral terms (and hyperosmotic response, retained separately). A generic stress-response term overstates and misframes this sensory role. worm/odr-3 GO:0031849 olfactory receptor binding ARBA:ARBA00098049 ACCEPT leaf (0) 0 worm/odr-3 GO:0043025 neuronal cell body ARBA:ARBA00027467 KEEP_AS_NON_CORE specific (1-20) 5 worm/odr-3 GO:0097730 non-motile cilium ARBA:ARBA00026428 ACCEPT specific (1-20) 18 worm/osm-1 GO:0030990 intraciliary transport particle ARBA:ARBA00050083 ACCEPT specific (1-20) 2 worm/osm-1 GO:0044782 cilium organization ARBA:ARBA00027540 ACCEPT general (21-200) 28 worm/osm-3 GO:0032991 protein-containing complex ARBA:ARBA00028902 MODIFY very general (>200 descendants) 2083 NEEDS_MORE_SPECIFIC true but uninformative replacement term Too general. OSM-3 specifically forms kinesin complexes. worm/pdk-1 GO:0048638 regulation of developmental growth ARBA:ARBA00091468 MARK_AS_OVER_ANNOTATED general (21-200) 111 UNCLASSIFIED unclassified Machine-learned term without specific evidence for PDK-1 controlling growth per se in C. elegans; developmental roles are captured by dauer terms. worm/pdk-1 GO:0160108 animal gross anatomical part developmental process ARBA:ARBA00098139 MARK_AS_OVER_ANNOTATED very general (>200 descendants) 3010 TOO_GENERAL true but uninformative Vague Vague machine-learned term without specific supporting evidence. worm/pdk-1 GO:1901701 cellular response to oxygen-containing compound ARBA:ARBA00027483 MARK_AS_OVER_ANNOTATED very general (>200 descendants) 308 TOO_GENERAL true but uninformative Vague Vague machine-learned term; not a demonstrated PDK-1 function. worm/pdr-1 GO:0009893 positive regulation of metabolic process ARBA:ARBA00028097 MARK_AS_OVER_ANNOTATED very general (>200 descendants) 739 TOO_GENERAL true but uninformative broad Overly broad annotation from machine learning. Does not provide useful functional information about PDR-1's specific role in ubiquitination and mitophagy. worm/pek-1 GO:0034976 response to endoplasmic reticulum stress ARBA:ARBA00027479 ACCEPT general (21-200) 23 worm/pfd-3 GO:0005737 cytoplasm ARBA:ARBA00026971 ACCEPT very general (>200 descendants) 1146 worm/phb-1 GO:0002082 regulation of oxidative phosphorylation ARBA:ARBA00088025 KEEP_AS_NON_CORE specific (1-20) 4 worm/phb-1 GO:0006979 response to oxidative stress ARBA:ARBA00026273 KEEP_AS_NON_CORE general (21-200) 42 worm/phb-1 GO:0007283 spermatogenesis ARBA:ARBA00085131 KEEP_AS_NON_CORE general (21-200) 28 worm/phb-1 GO:0008406 gonad development ARBA:ARBA00028782 KEEP_AS_NON_CORE general (21-200) 32 worm/phb-1 GO:0009792 embryo development ending in birth or egg hatching ARBA:ARBA00029005 KEEP_AS_NON_CORE general (21-200) 122 worm/phb-1 GO:0030421 defecation ARBA:ARBA00087140 KEEP_AS_NON_CORE specific (1-20) 1 worm/phb-1 GO:0040018 positive regulation of multicellular organism growth ARBA:ARBA00086734 KEEP_AS_NON_CORE leaf (0) 0 worm/phb-1 GO:0043051 regulation of nematode pharyngeal pumping ARBA:ARBA00084837 KEEP_AS_NON_CORE specific (1-20) 2 worm/phb-1 GO:0048477 oogenesis ARBA:ARBA00028681 KEEP_AS_NON_CORE general (21-200) 81 worm/phb-2 GO:0002082 regulation of oxidative phosphorylation ARBA:ARBA00088025 KEEP_AS_NON_CORE specific (1-20) 4 worm/phb-2 GO:0005739 mitochondrion ARBA:ARBA00026962 KEEP_AS_NON_CORE general (21-200) 70 worm/phb-2 GO:0006979 response to oxidative stress ARBA:ARBA00026273 KEEP_AS_NON_CORE general (21-200) 42 worm/phb-2 GO:0007283 spermatogenesis ARBA:ARBA00085131 KEEP_AS_NON_CORE general (21-200) 28 worm/phb-2 GO:0008406 gonad development ARBA:ARBA00028782 KEEP_AS_NON_CORE general (21-200) 32 worm/phb-2 GO:0009792 embryo development ending in birth or egg hatching ARBA:ARBA00029005 KEEP_AS_NON_CORE general (21-200) 122 worm/phb-2 GO:0030421 defecation ARBA:ARBA00087140 KEEP_AS_NON_CORE specific (1-20) 1 worm/phb-2 GO:0040018 positive regulation of multicellular organism growth ARBA:ARBA00086734 KEEP_AS_NON_CORE leaf (0) 0 worm/phb-2 GO:0043051 regulation of nematode pharyngeal pumping ARBA:ARBA00084837 KEEP_AS_NON_CORE specific (1-20) 2 worm/phb-2 GO:0048477 oogenesis ARBA:ARBA00028681 KEEP_AS_NON_CORE general (21-200) 81 worm/pink-1 GO:0006950 response to stress ARBA:ARBA00026300 ACCEPT very general (>200 descendants) 590 worm/pmk-1 GO:0000302 response to reactive oxygen species ARBA:ARBA00027603 ACCEPT general (21-200) 22 worm/pmk-1 GO:0005737 cytoplasm ARBA:ARBA00026971 ACCEPT very general (>200 descendants) 1146 worm/pmk-1 GO:0006955 immune response ARBA:ARBA00026313 ACCEPT very general (>200 descendants) 207 worm/pmk-1 GO:0006970 response to osmotic stress ARBA:ARBA00026252 ACCEPT general (21-200) 29 worm/pmk-1 GO:0007165 signal transduction ARBA:ARBA00029050 ACCEPT very general (>200 descendants) 937 worm/pmk-1 GO:0009408 response to heat ARBA:ARBA00028092 KEEP_AS_NON_CORE specific (1-20) 7 worm/pmk-1 GO:0042742 defense response to bacterium ARBA:ARBA00028625 ACCEPT specific (1-20) 19 worm/pmk-1 GO:0050832 defense response to fungus ARBA:ARBA00029244 ACCEPT specific (1-20) 6 worm/pmk-1 GO:0071248 cellular response to metal ion ARBA:ARBA00028718 KEEP_AS_NON_CORE general (21-200) 29 worm/pmk-1 GO:0080135 regulation of cellular response to stress ARBA:ARBA00026867 ACCEPT general (21-200) 167 worm/prg-1 GO:0007279 pole cell formation ARBA:ARBA00085029 REMOVE leaf (0) 0 WRONG_TAXON wrong manual WRONG_TAXON This is an erroneous ARBA machine learning annotation. Pole cell formation (GO:0007279) is explicitly defined as an insect process occurring in blastula stage, which is not applicable to C. elegans developmental biology. C. elegans germ cell specification occurs through different mechanisms. worm/prg-1 GO:0009994 oocyte differentiation ARBA:ARBA00084567 KEEP_AS_NON_CORE general (21-200) 34 worm/prg-1 GO:0010526 transposable element silencing ARBA:ARBA00092295 ACCEPT specific (1-20) 8 worm/prg-1 GO:0034584 piRNA binding ARBA:ARBA00092433 ACCEPT leaf (0) 0 worm/prg-1 GO:0034587 piRNA processing ARBA:ARBA00047257 UNDECIDED specific (1-20) 2 worm/prg-1 GO:0140991 piRNA-mediated gene silencing by mRNA destabilization ARBA:ARBA00087016 MODIFY specific (1-20) 1 TOO_SPECIFIC overreach replacement term While PRG-1 is involved in gene silencing, the mechanism in C. elegans primarily involves triggering secondary siRNA production (22G-RNAs via the WAGO pathway) rather than direct mRNA destabilization by PRG-1 itself. Primary work shows that loss of PRG-1 depletes RdRP-derived secondary 22G-RNAs at target loci with concomitant mRNA de-repression, and that PRG-1 initiates but does not maintain silencing (Lee et al. 2012, PMID:22738724) — so a term implying direct PIWI-endonuclease mRNA destabilization mis-describes the worm mechanism. The parent term GO:0031047 (regulatory ncRNA-mediated gene silencing) is more appropriate. worm/ric-4 GO:0005484 helical-bundle zippering fusogenic activity ARBA:ARBA00027977 ACCEPT leaf (0) 0 worm/ric-4 GO:0006887 exocytosis ARBA:ARBA00027178 ACCEPT general (21-200) 44 worm/ric-4 GO:0031201 SNARE complex ARBA:ARBA00028851 ACCEPT specific (1-20) 18 worm/sdf-9 GO:0040024 dauer larval development ARBA:ARBA00086745 ACCEPT specific (1-20) 3 worm/sek-1 GO:0000165 MAPK cascade ARBA:ARBA00029221 ACCEPT specific (1-20) 18 worm/sem-5 GO:0005154 epidermal growth factor receptor binding ARBA:ARBA00085861 ACCEPT leaf (0) 0 worm/sem-5 GO:0007173 epidermal growth factor receptor signaling pathway ARBA:ARBA00034174 ACCEPT specific (1-20) 3 worm/sir-2.1 GO:0004407 histone deacetylase activity ARBA:ARBA00026972 MODIFY specific (1-20) 17 NEEDS_MORE_SPECIFIC true but uninformative replacement term While correct, this term is too general. SIR-2.1 specifically has NAD-dependent histone deacetylase activity (GO:0017136). The more specific term should be used. worm/skn-1 GO:0010468 regulation of gene expression ARBA:ARBA00028334 ACCEPT very general (>200 descendants) 874 worm/sma-2 GO:0009791 post-embryonic development ARBA:ARBA00029007 KEEP_AS_NON_CORE very general (>200 descendants) 271 worm/sma-2 GO:0050793 regulation of developmental process ARBA:ARBA00028689 KEEP_AS_NON_CORE very general (>200 descendants) 1542 worm/sma-2 GO:0051239 regulation of multicellular organismal process ARBA:ARBA00028859 KEEP_AS_NON_CORE very general (>200 descendants) 1807 worm/sma-2 GO:0160108 animal gross anatomical part developmental process ARBA:ARBA00098139 KEEP_AS_NON_CORE very general (>200 descendants) 3010 worm/sma-3 GO:0009791 post-embryonic development ARBA:ARBA00029007 KEEP_AS_NON_CORE very general (>200 descendants) 271 worm/sma-3 GO:0045595 regulation of cell differentiation ARBA:ARBA00028479 KEEP_AS_NON_CORE very general (>200 descendants) 697 worm/sma-3 GO:0045944 positive regulation of transcription by RNA polymerase II ARBA:ARBA00027996 ACCEPT specific (1-20) 12 worm/sma-3 GO:0048639 positive regulation of developmental growth ARBA:ARBA00091477 ACCEPT general (21-200) 31 worm/sma-3 GO:0048731 system development ARBA:ARBA00027702 KEEP_AS_NON_CORE very general (>200 descendants) 2438 worm/sma-3 GO:0051240 positive regulation of multicellular organismal process ARBA:ARBA00028891 KEEP_AS_NON_CORE very general (>200 descendants) 565 worm/sma-3 GO:0090066 regulation of anatomical structure size ARBA:ARBA00029178 ACCEPT general (21-200) 127 worm/sma-3 GO:0090596 sensory organ morphogenesis ARBA:ARBA00043576 KEEP_AS_NON_CORE general (21-200) 116 worm/sma-4 GO:0008340 determination of adult lifespan ARBA:ARBA00026742 UNDECIDED leaf (0) 0 worm/sma-4 GO:0040024 dauer larval development ARBA:ARBA00086745 UNDECIDED specific (1-20) 3 worm/sma-4 GO:0048639 positive regulation of developmental growth ARBA:ARBA00091477 ACCEPT general (21-200) 31 worm/sma-4 GO:0051240 positive regulation of multicellular organismal process ARBA:ARBA00028891 KEEP_AS_NON_CORE very general (>200 descendants) 565 worm/sma-9 GO:0003714 transcription corepressor activity ARBA:ARBA00089152 ACCEPT specific (1-20) 1 worm/sma-9 GO:0071363 cellular response to growth factor stimulus ARBA:ARBA00027976 KEEP_AS_NON_CORE general (21-200) 50 worm/sma-9 GO:0141091 transforming growth factor beta receptor superfamily signaling pathway ARBA:ARBA00043534 ACCEPT specific (1-20) 10 worm/snb-1 GO:0016079 synaptic vesicle exocytosis ARBA:ARBA00028976 ACCEPT specific (1-20) 9 worm/snt-1 GO:0007626 locomotory behavior ARBA:ARBA00086008 KEEP_AS_NON_CORE specific (1-20) 15 worm/snt-1 GO:0008021 synaptic vesicle ARBA:ARBA00029077 ACCEPT specific (1-20) 7 worm/snt-1 GO:0048488 synaptic vesicle endocytosis ARBA:ARBA00091614 ACCEPT specific (1-20) 5 worm/sod-2 GO:0098803 respiratory chain complex ARBA:ARBA00029130 KEEP_AS_NON_CORE specific (1-20) 8 worm/sod-3 GO:0098803 respiratory chain complex ARBA:ARBA00029130 KEEP_AS_NON_CORE specific (1-20) 8 worm/spg-7 GO:0051604 protein maturation ARBA:ARBA00026902 ACCEPT general (21-200) 74 worm/sup-17 GO:0005737 cytoplasm ARBA:ARBA00026971 MARK_AS_OVER_ANNOTATED very general (>200 descendants) 1146 TOO_GENERAL true but uninformative uninformative SUP-17 is a single-pass type I membrane protein at the plasma membrane and in intracellular vesicle puncta. 'Cytoplasm' is not strictly wrong (vesicles are in the cytoplasm) but is uninformative and misleading for a transmembrane protease; the plasma membrane and cytoplasmic vesicle membrane annotations capture its location. worm/sup-17 GO:0043226 organelle ARBA:ARBA00029065 MARK_AS_OVER_ANNOTATED very general (>200 descendants) 1881 TOO_GENERAL true but uninformative Uninformative Uninformative high-level location; the specific plasma membrane and vesicle membrane annotations describe SUP-17 location. worm/tax-4 GO:0034703 cation channel complex ARBA:ARBA00028870 ACCEPT general (21-200) 32 worm/tax-4 GO:0070482 response to oxygen levels ARBA:ARBA00029157 KEEP_AS_NON_CORE general (21-200) 24 worm/tir-1 GO:0019677 NAD+ catabolic process ARBA:ARBA00028167 ACCEPT leaf (0) 0 worm/tir-1 GO:0044297 cell body ARBA:ARBA00028356 ACCEPT specific (1-20) 9 worm/ufd-1 GO:0010498 proteasomal protein catabolic process ARBA:ARBA00028386 ACCEPT general (21-200) 21 worm/unc-1 GO:0043005 neuron projection ARBA:ARBA00027418 ACCEPT general (21-200) 135 worm/unc-11 GO:0006898 receptor-mediated endocytosis ARBA:ARBA00044584 ACCEPT general (21-200) 30 worm/unc-11 GO:0040011 locomotion ARBA:ARBA00026452 KEEP_AS_NON_CORE general (21-200) 95 worm/unc-11 GO:0048488 synaptic vesicle endocytosis ARBA:ARBA00091614 ACCEPT specific (1-20) 5 worm/unc-18 GO:0006887 exocytosis ARBA:ARBA00027178 ACCEPT general (21-200) 44 worm/unc-18 GO:0051650 establishment of vesicle localization ARBA:ARBA00033964 ACCEPT general (21-200) 39 worm/unc-2 GO:0009581 detection of external stimulus ARBA:ARBA00027562 MARK_AS_OVER_ANNOTATED general (21-200) 45 INDIRECT_EFFECT overreach downstream This class of term reflects vertebrate CaV paralogs with dedicated sensory-transduction roles (for example CaV1.4 in photoreceptors and CaV1.3 in hair cells). Worm UNC-2 is the presynaptic CaV2 channel; although it is expressed in sensory neurons, its documented job there is transmitter release and downstream calcium signalling, not stimulus detection. worm/unc-2 GO:0009582 detection of abiotic stimulus ARBA:ARBA00027563 MARK_AS_OVER_ANNOTATED general (21-200) 46 WRONG_PARALOG wrong paralog As for detection of external stimulus - the term derives from sensory-transduction roles of vertebrate CaV paralogs and does not describe what worm UNC-2 does at the presynaptic active zone. worm/unc-2 GO:0016322 neuron remodeling ARBA:ARBA00086716 MARK_AS_OVER_ANNOTATED leaf (0) 0 TOO_GENERAL true but uninformative general No C. elegans evidence connects UNC-2 to neuronal remodeling, and the channel's characterized roles are acute calcium influx for release and calcium signalling. The term generalizes activity-dependent structural plasticity documented for other family members. worm/unc-2 GO:0016323 basolateral plasma membrane ARBA:ARBA00086715 MARK_AS_OVER_ANNOTATED leaf (0) 0 WRONG_PARALOG wrong paralog A polarized epithelial-membrane domain is not where a neuronal presynaptic channel acts; UNC-2 is documented at the presynaptic active-zone membrane. The term is an epithelial-paralog artifact of the family rule. worm/unc-2 GO:0019722 calcium-mediated signaling ARBA:ARBA00027115 ACCEPT general (21-200) 22 worm/unc-2 GO:0042045 epithelial fluid transport ARBA:ARBA00086211 MARK_AS_OVER_ANNOTATED specific (1-20) 2 TOO_GENERAL true but uninformative broad Neither C. elegans nor vertebrate CaV2 channels are epithelial fluid-transport components; the term reflects other members of the broad calcium-channel alpha1 family. Nothing in the worm literature places UNC-2 in an epithelium. worm/unc-2 GO:0042734 presynaptic membrane ARBA:ARBA00088391 ACCEPT specific (1-20) 6 worm/unc-2 GO:0050906 detection of stimulus involved in sensory perception ARBA:ARBA00028231 MARK_AS_OVER_ANNOTATED general (21-200) 37 UNCLASSIFIED unclassified The third of the rule-derived sensory-transduction terms. UNC-2 is present in sensory neurons but acts there as the presynaptic calcium source and as an upstream calcium signal, not as the receptor/transducer that detects the stimulus. worm/unc-41 GO:0045202 synapse ARBA:ARBA00027462 ACCEPT general (21-200) 142 worm/unc-51 GO:0006914 autophagy ARBA:ARBA00027757 ACCEPT general (21-200) 49 worm/unc-57 GO:0016192 vesicle-mediated transport ARBA:ARBA00028249 ACCEPT very general (>200 descendants) 232 worm/unc-64 GO:0007269 neurotransmitter secretion ARBA:ARBA00028186 ACCEPT general (21-200) 32 worm/unc-84 GO:0005635 nuclear envelope ARBA:ARBA00026328 ACCEPT general (21-200) 29 worm/vha-1 GO:0007042 lysosomal lumen acidification ARBA:ARBA00092063 ACCEPT leaf (0) 0 worm/vps-34 GO:0160108 animal gross anatomical part developmental process ARBA:ARBA00098139 MARK_AS_OVER_ANNOTATED very general (>200 descendants) 3010 INDIRECT_EFFECT overreach phenotype This is a vague developmental grouping term with no specific supporting evidence. Developmental phenotypes of vps-34 are pleiotropic results of its trafficking role. worm/zip-2 GO:0050829 defense response to Gram-negative bacterium ARBA:ARBA00029238 ACCEPT specific (1-20) 2 worm/znfx-1 GO:0005694 chromosome ARBA:ARBA00026361 REMOVE very general (>200 descendants) 204 WRONG_LOCATION wrong manual WRONG_LOCATION No experimental evidence supports chromosome localization. The protein functions in cytoplasmic RNA granules and perinuclear nuage. This appears to be an erroneous inference. yeast/AAD3 GO:0047681 aryl-alcohol dehydrogenase (NADP+) activity ARBA:ARBA00093038 REMOVE leaf (0) 0 NONCATALYTIC_HOMOLOG wrong manual NONCATALYTIC_HOMOLOG This is a demonstrably wrong electronic transfer. The rule assigns the family activity to every AAD-like sequence, but the only biochemical study of the AAD3 protein itself (Yang et al. 2018) found it catalytically inactive across the aryl-aldehyde substrate panel, identified a substitution at the catalytic-site tyrosine, and showed that correcting that substitution still yields no active enzyme, i.e. AAD3 has accumulated additional inactivating changes and is pseudogenizing. The earlier family-wide deletion data (no aryl-aldehyde phenotype) and the failure of AAD3 overexpression to raise extract activity are consistent with this. An annotation asserting the specific enzymatic activity is therefore contradicted, not merely over-specific, and should be removed rather than generalized. yeast/ADE3 GO:0006760 folic acid-containing compound metabolic process ARBA:ARBA00027960 ACCEPT specific (1-20) 17 yeast/ADE3 GO:0055086 nucleobase-containing small molecule metabolic process ARBA:ARBA00027681 MARK_AS_OVER_ANNOTATED very general (>200 descendants) 576 INDIRECT_EFFECT overreach Indirect Indirect: the enzyme provides a C1 cofactor, the nucleotide chemistry is done by other enzymes. yeast/ADE3 GO:0072522 purine-containing compound biosynthetic process ARBA:ARBA00026861 KEEP_AS_NON_CORE general (21-200) 112 yeast/AGX1 GO:0008483 transaminase activity ARBA:ARBA00028950 KEEP_AS_NON_CORE general (21-200) 91 yeast/AIM33 GO:0004128 cytochrome-b5 reductase activity, acting on NAD(P)H ARBA:ARBA00027922 MARK_AS_OVER_ANNOTATED specific (1-20) 2 TOO_GENERAL true but uninformative general This ARBA rule fires on family/domain features shared across the CYB5R superfamily and assigns the specific cytochrome-b5 acceptor. As with the IBA, the reductase fold is present but the cytochrome-b5 acceptor is not verified for AIM33; the defensible electronic MF is the general oxidoreductase activity (GO:0016491), which is separately annotated and retained. yeast/ALD2 GO:0004030 aldehyde dehydrogenase [NAD(P)+] activity ARBA:ARBA00028733 KEEP_AS_NON_CORE general (21-200) 54 yeast/ALD2 GO:0046394 carboxylic acid biosynthetic process ARBA:ARBA00027883 KEEP_AS_NON_CORE very general (>200 descendants) 208 yeast/ALO1 GO:0005739 mitochondrion ARBA:ARBA00026962 KEEP_AS_NON_CORE general (21-200) 70 yeast/ALO1 GO:0034599 cellular response to oxidative stress ARBA:ARBA00027632 KEEP_AS_NON_CORE general (21-200) 25 yeast/ATG7 GO:0016237 microautophagy ARBA:ARBA00027243 MARK_AS_OVER_ANNOTATED specific (1-20) 5 TOO_GENERAL true but uninformative generic Marked as over-annotated because ATG7 is strongly supported for nucleophagy (piecemeal microautophagy of nucleus), while generic microautophagy is less specifically evidenced. yeast/BNA2 GO:0016702 oxidoreductase activity, acting on single donors with incorporation of molecular oxygen, incorporation of two atoms of oxygen ARBA:ARBA00027642 MODIFY general (21-200) 72 NEEDS_MORE_SPECIFIC true but uninformative replacement term Generic parent of the specific activity. yeast/BTT1 GO:0005854 nascent polypeptide-associated complex ARBA:ARBA00088588 ACCEPT leaf (0) 0 yeast/BTT1 GO:0006613 cotranslational protein targeting to membrane ARBA:ARBA00087310 ACCEPT specific (1-20) 4 yeast/BUD16 GO:0042364 water-soluble vitamin biosynthetic process ARBA:ARBA00029043 MODIFY specific (1-20) 19 NEEDS_MORE_SPECIFIC true but uninformative replacement term Too general; the specific process is PLP salvage. yeast/CAB5 GO:0005737 cytoplasm ARBA:ARBA00026971 ACCEPT very general (>200 descendants) 1146 yeast/CBR1 GO:0003954 NADH dehydrogenase activity ARBA:ARBA00088748 MODIFY specific (1-20) 4 OTHER_TERM different term needed replacement term Cbr1 is experimentally characterized as an FAD-containing NADH:ferricytochrome-b5 reductase with EC 1.6.2.2 activity. GO:0003954 omits the cytochrome-b5 acceptor and is an avoidably broad parent beside the GO:0090524 row. yeast/CBR1 GO:0004128 cytochrome-b5 reductase activity, acting on NAD(P)H ARBA:ARBA00027922 MODIFY specific (1-20) 2 NEEDS_MORE_SPECIFIC true but uninformative replacement term Cbr1 has direct biochemical evidence for NADH-dependent cytochrome-b5 reduction and lacks evidence for an NADPH-dependent cytochrome-b5 reaction, so GO:0090524 is the best replacement for this broader GO:0004128 prediction. yeast/CCT3 GO:0005832 chaperonin-containing T-complex ARBA:ARBA00029273 ACCEPT leaf (0) 0 yeast/CCT4 GO:0005832 chaperonin-containing T-complex ARBA:ARBA00029273 ACCEPT leaf (0) 0 yeast/CCT5 GO:0005832 chaperonin-containing T-complex ARBA:ARBA00029273 ACCEPT leaf (0) 0 yeast/CCT6 GO:0005832 chaperonin-containing T-complex ARBA:ARBA00029273 ACCEPT leaf (0) 0 yeast/CCT7 GO:0005832 chaperonin-containing T-complex ARBA:ARBA00029273 ACCEPT leaf (0) 0 yeast/CCT8 GO:0005832 chaperonin-containing T-complex ARBA:ARBA00029273 ACCEPT leaf (0) 0 yeast/CDC14 GO:0000278 mitotic cell cycle ARBA:ARBA00028458 ACCEPT general (21-200) 121 yeast/CDC14 GO:0004721 phosphoprotein phosphatase activity ARBA:ARBA00027651 ACCEPT general (21-200) 36 yeast/CDC14 GO:0005816 spindle pole body ARBA:ARBA00029126 ACCEPT specific (1-20) 18 yeast/CDC14 GO:0007096 regulation of exit from mitosis ARBA:ARBA00092142 ACCEPT specific (1-20) 3 yeast/CDC14 GO:0032954 regulation of cytokinetic process ARBA:ARBA00087459 ACCEPT general (21-200) 33 yeast/CDC14 GO:0033554 cellular response to stress ARBA:ARBA00028184 KEEP_AS_NON_CORE very general (>200 descendants) 285 yeast/CDC16 GO:0005680 anaphase-promoting complex ARBA:ARBA00043276 ACCEPT leaf (0) 0 yeast/CDC20 GO:0031145 anaphase-promoting complex-dependent catabolic process ARBA:ARBA00034936 ACCEPT leaf (0) 0 yeast/CDC28 GO:0000082 G1/S transition of mitotic cell cycle ARBA:ARBA00028571 ACCEPT leaf (0) 0 yeast/CDC28 GO:0000307 cyclin-dependent protein kinase holoenzyme complex ARBA:ARBA00027596 ACCEPT general (21-200) 29 yeast/CDC28 GO:0006355 regulation of DNA-templated transcription ARBA:ARBA00028138 KEEP_AS_NON_CORE general (21-200) 140 yeast/CDC28 GO:0010570 regulation of filamentous growth ARBA:ARBA00027572 KEEP_AS_NON_CORE general (21-200) 34 yeast/CDC53 GO:0019005 SCF ubiquitin ligase complex ARBA:ARBA00091951 ACCEPT specific (1-20) 18 yeast/CDC53 GO:0031146 SCF-dependent proteasomal ubiquitin-dependent protein catabolic process ARBA:ARBA00084384 ACCEPT leaf (0) 0 yeast/CDC55 GO:0010972 negative regulation of G2/M transition of mitotic cell cycle ARBA:ARBA00084549 MODIFY specific (1-20) 5 TOO_SPECIFIC overreach replacement term The sign of this transfer is wrong for budding yeast. The experimental literature is explicit that PP2A-Cdc55 promotes, rather than prevents, timely entry into mitosis, by dephosphorylating and activating Mih1 and by opposing Swe1 activation; cdc55Δ cells accumulate Tyr19-phosphorylated Cdk1 and delay G2/M. The only sense in which Cdc55 restrains entry is as the Zds1/Zds2-controlled component required for the Swe1-dependent morphogenesis-checkpoint delay (the IGI rows below), a context-dependent effect that is not what the ARBA rule is describing. Rather than remove the row outright, it is generalised to the sign-neutral parent so that the machine annotation stops asserting the metazoan direction; the positive-regulation IMP row remains the core statement. yeast/CDC55 GO:1902531 regulation of intracellular signal transduction ARBA:ARBA00027126 MODIFY very general (>200 descendants) 278 NEEDS_MORE_SPECIFIC true but uninformative replacement term Not wrong, but too general to be informative. The concrete signalling pathway PP2A-Cdc55 is known to regulate in budding yeast is the spindle assembly checkpoint (GO:0090266, an experimentally supported descendant of this term via the IMP rows), so the row should be resolved to that descendant rather than kept as a bare ancestor. Its other regulatory roles (Cdk1 activation at G2/M, Cdc14 release at mitotic exit) are already carried by specific experimental rows. yeast/CHD1 GO:0000123 histone acetyltransferase complex ARBA:ARBA00029134 ACCEPT specific (1-20) 19 yeast/CHD1 GO:0006366 transcription by RNA polymerase II ARBA:ARBA00028158 ACCEPT specific (1-20) 19 yeast/CHD1 GO:0010468 regulation of gene expression ARBA:ARBA00028334 ACCEPT very general (>200 descendants) 874 yeast/CHD1 GO:0034728 nucleosome organization ARBA:ARBA00085234 ACCEPT specific (1-20) 2 yeast/CHD1 GO:0140658 ATP-dependent chromatin remodeler activity ARBA:ARBA00085709 ACCEPT specific (1-20) 5 yeast/CLN2 GO:0000307 cyclin-dependent protein kinase holoenzyme complex ARBA:ARBA00027596 ACCEPT general (21-200) 29 yeast/CLN2 GO:0007089 traversing start control point of mitotic cell cycle ARBA:ARBA00092120 ACCEPT leaf (0) 0 yeast/CLN2 GO:0016538 cyclin-dependent protein serine/threonine kinase regulator activity ARBA:ARBA00027788 MODIFY specific (1-20) 2 NEEDS_MORE_SPECIFIC true but uninformative replacement term The automated inference is correct but stops at the generic parent; the experimental evidence shows Cln2 is an activator of Cdc28, so the activator child term (GO:0061575) proposed on the IBA and IDA rows is the consistent replacement. yeast/CLN3 GO:0016538 cyclin-dependent protein serine/threonine kinase regulator activity ARBA:ARBA00027788 MODIFY specific (1-20) 2 NEEDS_MORE_SPECIFIC true but uninformative replacement term The automated inference is correct but stops at the generic parent; the experimental evidence (active Cln3-Cdc28 kinase complexes, CLN3-driven activation of Start) shows Cln3 is an activator of Cdc28, so the same activator child term (GO:0061575) proposed on the IBA, IDA and IMP rows is the consistent replacement. yeast/CLN3 GO:0044772 mitotic cell cycle phase transition ARBA:ARBA00027525 MODIFY specific (1-20) 4 NEEDS_MORE_SPECIFIC true but uninformative replacement term The specific transition is well established experimentally and already annotated (GO:0000082); the generic parent should be replaced by it. yeast/CPR6 GO:0042026 protein refolding ARBA:ARBA00043587 ACCEPT leaf (0) 0 yeast/CPR6 GO:0051082 unfolded protein binding ARBA:ARBA00027557 MODIFY leaf (0) 0 OTHER_TERM different term needed replacement term "GO:0051082 is obsolete, so it cannot be retained as-is. GO:0044183 (protein folding chaperone) is defined simply as ""Binding to a protein or a protein-containing complex to assist the protein folding process"" with no ATP-dependence requirement, so it is not restricted to ATP-dependent chaperones (the ATP-dependent foldase term is the separate GO:0140662). Direct yeast evidence supports a folding-chaperone term rather than discarding the annotation: the abstract of PMID:10942767 reports that CPR6 possesses chaperone activity, and SGD independently made a GO:0042026 (protein refolding) IDA on that same paper, which this review ACCEPTs elsewhere in this file. The closest precedent is the direct paralog CPR7, whose IEA and IDA GO:0051082 rows — from the same paper — are both already MODIFY to GO:0044183 (genes/yeast/CPR7/CPR7-ai-review.yaml). Caveat: PMID:10942767 is cached abstract-only (full_text_available: false), so the abstract cannot by itself discriminate foldase activity (GO:0044183) from in-situ aggregation prevention (GO:0140309, unfolded protein holdase activity); GO:0044183 is chosen for consistency with the CPR7 decision and with the curator-asserted GO:0042026 refolding annotation, and that discrimination is deferred pending full text." yeast/CPR7 GO:0042026 protein refolding ARBA:ARBA00043587 ACCEPT leaf (0) 0 yeast/CPR7 GO:0051082 unfolded protein binding ARBA:ARBA00027557 MODIFY leaf (0) 0 OTHER_TERM different term needed replacement term Unfolded protein binding is too broad; Cpr7 is better represented as a chaperone/co-chaperone component of the Hsp90 folding machinery. yeast/CRH1 GO:0009277 fungal-type cell wall ARBA:ARBA00026912 ACCEPT specific (1-20) 11 yeast/CRH1 GO:0031505 fungal-type cell wall organization ARBA:ARBA00026542 ACCEPT specific (1-20) 4 yeast/CYC1 GO:0006122 mitochondrial electron transport, ubiquinol to cytochrome c ARBA:ARBA00084238 ACCEPT leaf (0) 0 yeast/CYC1 GO:0006123 mitochondrial electron transport, cytochrome c to oxygen ARBA:ARBA00084245 ACCEPT leaf (0) 0 yeast/CYS4 GO:0000096 sulfur amino acid metabolic process ARBA:ARBA00028668 ACCEPT general (21-200) 23 yeast/CYS4 GO:0044272 sulfur compound biosynthetic process ARBA:ARBA00028512 ACCEPT general (21-200) 74 yeast/DBP5 GO:0010467 gene expression ARBA:ARBA00028330 MARK_AS_OVER_ANNOTATED very general (>200 descendants) 724 TOO_GENERAL true but uninformative broad While DBP5 is involved in the post-transcriptional steps of gene expression, this annotation is overly broad and generic. DBP5 is not directly involved in transcription, translation initiation, or other early gene expression steps. The term obscures the specific mRNA export function. yeast/DNM1 GO:0000266 mitochondrial fission ARBA:ARBA00090200 ACCEPT specific (1-20) 1 yeast/DNM1 GO:0005777 peroxisome ARBA:ARBA00028589 ACCEPT specific (1-20) 16 yeast/DNM1 GO:0005829 cytosol ARBA:ARBA00029243 ACCEPT general (21-200) 73 yeast/DNM1 GO:0016559 peroxisome fission ARBA:ARBA00027945 ACCEPT leaf (0) 0 yeast/DNM1 GO:0030001 metal ion transport ARBA:ARBA00028072 REMOVE very general (>200 descendants) 347 SPURIOUS_SIGNATURE wrong manual SPURIOUS_SIGNATURE No evidence that Dnm1 transports metal ions; an ARBA rule artefact with no biological basis for this GTPase. yeast/DNM1 GO:0042802 identical protein binding ARBA:ARBA00027930 KEEP_AS_NON_CORE specific (1-20) 1 yeast/DNM1 GO:0048311 mitochondrion distribution ARBA:ARBA00089905 KEEP_AS_NON_CORE specific (1-20) 3 yeast/ECM31 GO:0072330 monocarboxylic acid biosynthetic process ARBA:ARBA00027175 MODIFY general (21-200) 95 NEEDS_MORE_SPECIFIC true but uninformative replacement term IEA from ARBA rule ARBA00027175 (monocarboxylic acid biosynthetic process). Correct but very general; pantothenate biosynthetic process (an is_a child) is the informative term and is already annotated. yeast/EFM6 GO:0008757 S-adenosylmethionine-dependent methyltransferase activity ARBA:ARBA00026462 ACCEPT very general (>200 descendants) 242 yeast/EGD1 GO:0005854 nascent polypeptide-associated complex ARBA:ARBA00088588 ACCEPT leaf (0) 0 yeast/EGD1 GO:0006613 cotranslational protein targeting to membrane ARBA:ARBA00087310 KEEP_AS_NON_CORE specific (1-20) 4 yeast/EPS1 GO:0005737 cytoplasm ARBA:ARBA00026971 REMOVE very general (>200 descendants) 1146 WRONG_LOCATION wrong manual WRONG_LOCATION Cytoplasm misrepresents the experimentally supported ER membrane localization and should not be retained. yeast/EPS1 GO:0012505 endomembrane system ARBA:ARBA00028953 MODIFY very general (>200 descendants) 357 NEEDS_MORE_SPECIFIC true but uninformative replacement term Replace broad ARBA localization with the specific experimentally supported ER membrane term. yeast/ESA1 GO:0010485 histone H4 acetyltransferase activity ARBA:ARBA00092693 ACCEPT specific (1-20) 4 yeast/ESA1 GO:0006357 regulation of transcription by RNA polymerase II ARBA:ARBA00028137 ACCEPT general (21-200) 56 yeast/ESA1 GO:0010629 negative regulation of gene expression ARBA:ARBA00026647 KEEP_AS_NON_CORE very general (>200 descendants) 274 yeast/ESA1 GO:0035267 NuA4 histone acetyltransferase complex ARBA:ARBA00027854 ACCEPT leaf (0) 0 yeast/ESA1 GO:0006974 DNA damage response ARBA:ARBA00026271 ACCEPT general (21-200) 95 yeast/ESP1 GO:0000280 nuclear division ARBA:ARBA00028466 MODIFY general (21-200) 120 NEEDS_MORE_SPECIFIC true but uninformative replacement term The prediction is not wrong but far too general: nuclear division covers mitosis and meiosis as a whole, whereas separase executes a single defined step. The informative term is mitotic sister chromatid separation (GO:0051306), already annotated experimentally. Graded as in the human ESPL1 review of the same ARBA rule. yeast/ESP1 GO:0098813 nuclear chromosome segregation ARBA:ARBA00027947 ACCEPT general (21-200) 80 yeast/EUG1 GO:0006457 protein folding ARBA:ARBA00027200 ACCEPT specific (1-20) 7 yeast/EUG1 GO:0015035 protein-disulfide reductase activity ARBA:ARBA00026550 ACCEPT specific (1-20) 4 yeast/EUG1 GO:0051082 unfolded protein binding UNDECIDED leaf (0) 0 yeast/EXG1 GO:0009277 fungal-type cell wall ARBA:ARBA00026912 ACCEPT specific (1-20) 11 yeast/FOL2 GO:0009396 folic acid-containing compound biosynthetic process ARBA:ARBA00029164 ACCEPT specific (1-20) 8 yeast/FUN19 GO:0010468 regulation of gene expression ARBA:ARBA00028334 ACCEPT very general (>200 descendants) 874 yeast/FUS3 GO:0000749 response to pheromone triggering conjugation with cellular fusion ARBA:ARBA00090899 ACCEPT specific (1-20) 2 yeast/FUS3 GO:0001403 invasive growth in response to glucose limitation ARBA:ARBA00090378 MODIFY leaf (0) 0 NEEDS_MORE_SPECIFIC true but uninformative replacement term Fus3 does not drive haploid invasive growth; it restrains it. Fus3 kinase activity blocks cross-activation of invasive-growth gene expression by the pheromone cascade (PMID:10652102), and Fus3 phosphorylates Tec1 to trigger its pheromone-induced destruction, so fus3 deletion causes erroneous invasive growth (PMID:15620357). The mutant phenotype is therefore evidence for negative regulation, and the positive process term misrepresents the direction of Fus3's role. The appropriate term is GO:2000218 negative regulation of invasive growth in response to glucose limitation (the same replacement is used for the paralog KSS1 review's repressive role). yeast/GCN5 GO:0006338 chromatin remodeling ARBA:ARBA00027994 ACCEPT very general (>200 descendants) 235 yeast/GCN5 GO:0010468 regulation of gene expression ARBA:ARBA00028334 MARK_AS_OVER_ANNOTATED very general (>200 descendants) 874 TOO_GENERAL true but uninformative broad This is an accurate but very broad parent term. GCN5 function is better captured by chromatin organization/remodeling and regulation of RNA polymerase II transcription annotations tied to histone acetylation. yeast/GCN5 GO:0010557 positive regulation of macromolecule biosynthetic process ARBA:ARBA00027412 MARK_AS_OVER_ANNOTATED very general (>200 descendants) 270 INDIRECT_EFFECT overreach indirect This is an indirect and overly broad downstream consequence of GCN5-dependent transcriptional regulation. More specific chromatin and RNA polymerase II transcription regulation terms should carry the functional interpretation. yeast/GCN5 GO:0140671 ADA complex ARBA:ARBA00085714 ACCEPT leaf (0) 0 yeast/HDA1 GO:0006355 regulation of DNA-templated transcription ARBA:ARBA00028138 ACCEPT general (21-200) 140 yeast/HDA1 GO:0010557 positive regulation of macromolecule biosynthetic process ARBA:ARBA00027412 REMOVE very general (>200 descendants) 270 WRONG_DIRECTION wrong manual WRONG_DIRECTION This annotation is mechanistically inconsistent with HDA1's documented function. HDA1 catalyzes histone deacetylation that typically promotes gene silencing and heterochromatin formation, resulting in negative regulation of transcription and suppression of biosynthetic processes. While HDA1 might positively regulate transcription at specific loci in particular cellular contexts, the predominant and well-characterized mechanism is transcriptional repression. The ARBA inference appears to contradict experimental evidence for HDA1's core function. yeast/HEM1 GO:0006783 heme biosynthetic process ARBA:ARBA00027909 ACCEPT specific (1-20) 5 yeast/HEM12 GO:0006778 porphyrin-containing compound metabolic process ARBA:ARBA00027898 MODIFY general (21-200) 33 NEEDS_MORE_SPECIFIC true but uninformative replacement term Too general. yeast/HEM13 GO:0006783 heme biosynthetic process ARBA:ARBA00027909 ACCEPT specific (1-20) 5 yeast/HEM3 GO:0006783 heme biosynthetic process ARBA:ARBA00027909 ACCEPT specific (1-20) 5 yeast/HRT1 GO:0010498 proteasomal protein catabolic process ARBA:ARBA00028386 ACCEPT general (21-200) 21 yeast/HRT1 GO:0031463 Cul3-RING ubiquitin ligase complex ARBA:ARBA00085910 ACCEPT leaf (0) 0 yeast/HSC82 GO:0000492 box C/D snoRNP assembly ARBA:ARBA00089701 KEEP_AS_NON_CORE leaf (0) 0 yeast/HSC82 GO:0043248 proteasome assembly ARBA:ARBA00028936 KEEP_AS_NON_CORE specific (1-20) 2 yeast/HSF1 GO:0032993 protein-DNA complex ARBA:ARBA00028896 KEEP_AS_NON_CORE general (21-200) 50 yeast/HSP10 GO:0005739 mitochondrion ARBA:ARBA00026962 ACCEPT general (21-200) 70 yeast/HSP104 GO:0005829 cytosol ARBA:ARBA00029243 ACCEPT general (21-200) 73 yeast/HSP104 GO:0006457 protein folding ARBA:ARBA00027200 MODIFY specific (1-20) 7 NEEDS_MORE_SPECIFIC true but uninformative replacement term "HSP104 does not participate in de novo protein folding. It specifically disaggregates and enables refolding of already-aggregated proteins. GO:0042026 ""protein refolding"" is the more precise term, consistent with the IDA annotation at PMID:9674429." yeast/HSP104 GO:0034605 cellular response to heat ARBA:ARBA00026567 ACCEPT specific (1-20) 3 yeast/HSP104 GO:0042802 identical protein binding ARBA:ARBA00027930 ACCEPT specific (1-20) 1 yeast/HSP104 GO:0043335 protein unfolding ARBA:ARBA00086271 ACCEPT leaf (0) 0 yeast/HSP104 GO:0070013 intracellular organelle lumen ARBA:ARBA00027917 MARK_AS_OVER_ANNOTATED very general (>200 descendants) 239 INDIRECT_EFFECT overreach indirect HSP104 is a cytosolic/nuclear protein. While it has been implicated in ER protein folding (PMID:10931304), this is likely an indirect effect from the cytosolic side. There is no evidence that HSP104 resides within organelle lumens. This ARBA annotation appears to be an over-interpretation. yeast/HSP26 GO:0006457 protein folding ARBA:ARBA00027200 MARK_AS_OVER_ANNOTATED specific (1-20) 7 UNCLASSIFIED unclassified "HSP26 is a holdase, not a foldase. It prevents aggregation of non-native proteins but does not actively catalyze protein folding. The GO:0006457 definition states ""assisting in the covalent and noncovalent assembly of single chain polypeptides or multisubunit complexes into the correct tertiary structure,"" which better describes ATP-dependent foldase chaperones like GroEL/ES or HSP70. HSP26 maintains substrates in a folding-competent state for later refolding by other chaperones. The IEA mapping is too generous here. A more appropriate BP annotation would be to a process term reflecting prevention of protein aggregation under stress." yeast/HSP60 GO:0005737 cytoplasm ARBA:ARBA00026971 REMOVE very general (>200 descendants) 1146 WRONG_LOCATION wrong manual WRONG_LOCATION HSP60 is a mitochondrial matrix protein. Cytoplasmic presence is only transient during import; the reported cytoplasmic pool is from mammalian studies, not yeast. yeast/HSP60 GO:0051082 unfolded protein binding ARBA:ARBA00027557 MODIFY leaf (0) 0 OTHER_TERM different term needed replacement term GO:0051082 is now formally obsolete. HSP60 is a bona fide ATP-dependent foldase chaperonin, not a passive unfolded protein binder. yeast/HSP78 GO:0006457 protein folding ARBA:ARBA00027200 MODIFY specific (1-20) 7 NEEDS_MORE_SPECIFIC true but uninformative replacement term Hsp78 is not a general de novo folding chaperone. It cooperates with the mitochondrial Hsp70 system to reactivate substrates after heat-induced aggregation, making GO:0042026 protein refolding the better process term. yeast/HSP78 GO:0034605 cellular response to heat ARBA:ARBA00026567 ACCEPT specific (1-20) 3 yeast/HSP78 GO:0043335 protein unfolding ARBA:ARBA00086271 ACCEPT leaf (0) 0 yeast/HSP78 GO:0070013 intracellular organelle lumen ARBA:ARBA00027917 MODIFY very general (>200 descendants) 239 NEEDS_MORE_SPECIFIC true but uninformative replacement term Hsp78 is not just somewhere in an organelle lumen; it is a soluble mitochondrial matrix disaggregase, as shown by submitochondrial fractionation and by the Hsp78-specific PAINT node. yeast/HSP82 GO:0000492 box C/D snoRNP assembly ARBA:ARBA00089701 KEEP_AS_NON_CORE leaf (0) 0 yeast/HSP82 GO:0043248 proteasome assembly ARBA:ARBA00028936 KEEP_AS_NON_CORE specific (1-20) 2 yeast/HST1 GO:0000785 chromatin ARBA:ARBA00027601 ACCEPT general (21-200) 86 yeast/HST1 GO:0017136 histone deacetylase activity, NAD-dependent ARBA:ARBA00027379 ACCEPT specific (1-20) 6 yeast/HST1 GO:0030466 silent mating-type cassette heterochromatin formation ARBA:ARBA00087185 KEEP_AS_NON_CORE specific (1-20) 1 yeast/HST1 GO:0031981 nuclear lumen ARBA:ARBA00026536 ACCEPT general (21-200) 139 yeast/HST1 GO:0045910 negative regulation of DNA recombination ARBA:ARBA00086129 UNDECIDED specific (1-20) 15 yeast/HST2 GO:0031507 heterochromatin formation ARBA:ARBA00033536 KEEP_AS_NON_CORE general (21-200) 25 yeast/HST3 GO:0017136 histone deacetylase activity, NAD-dependent ARBA:ARBA00027379 MODIFY specific (1-20) 6 NEEDS_MORE_SPECIFIC true but uninformative replacement term Use the specific child term GO:0140765 for HST3s demonstrated H3K56 deacetylase activity. yeast/HST3 GO:0031507 heterochromatin formation ARBA:ARBA00033536 KEEP_AS_NON_CORE general (21-200) 25 yeast/ILT1 GO:0016020 membrane ARBA:ARBA00028763 ACCEPT very general (>200 descendants) 895 yeast/IRE1 GO:0031505 fungal-type cell wall organization ARBA:ARBA00026542 KEEP_AS_NON_CORE specific (1-20) 4 yeast/KAR2 GO:0005737 cytoplasm KEEP_AS_NON_CORE very general (>200 descendants) 1146 yeast/KAR2 GO:0006616 SRP-dependent cotranslational protein targeting to membrane, translocation ARBA:ARBA00087312 ACCEPT leaf (0) 0 yeast/KAR2 GO:0051082 unfolded protein binding MODIFY leaf (0) 0 OTHER_TERM different term needed replacement term GO:0051082 is now formally obsolete. KAR2/BiP is an ATP-dependent protein folding chaperone; its binding to unfolded substrates is part of its chaperone mechanism, not a passive binding activity. Should be replaced with the chaperone function terms already annotated (GO:0044183 or GO:0140662). yeast/KAR2 GO:0030163 protein catabolic process ARBA:ARBA00027403 MODIFY general (21-200) 66 NEEDS_MORE_SPECIFIC true but uninformative replacement term The ARBA process row points to real Kar2p biology. Kar2p helps maintain misfolded ERAD substrates in a soluble, retrotranslocation-competent state and participates in the Yos9p/Kar2p/Hrd3p luminal surveillance complex (PMID:11381090, PMID:16873065). GO:0036503 ERAD quality control pathway is the specific live term already supported by IBA, NAS, and IMP rows. yeast/KAR2 GO:0033554 cellular response to stress ARBA:ARBA00028184 MODIFY very general (>200 descendants) 285 NEEDS_MORE_SPECIFIC true but uninformative replacement term Genetic analysis of kar2 mutants supports a direct role for Kar2p in Ire1 regulation during ER stress (PMID:12808051). The more specific GO:0030968 endoplasmic reticulum unfolded protein response term is already present on the live IBA row and better captures the stress pathway in which Kar2p acts. yeast/KDX1 GO:0007165 signal transduction ARBA:ARBA00029050 ACCEPT very general (>200 descendants) 937 yeast/KDX1 GO:0009272 fungal-type cell wall biogenesis ARBA:ARBA00033809 KEEP_AS_NON_CORE specific (1-20) 16 yeast/KSS1 GO:0000749 response to pheromone triggering conjugation with cellular fusion ARBA:ARBA00090899 ACCEPT specific (1-20) 2 yeast/KSS1 GO:0001403 invasive growth in response to glucose limitation ARBA:ARBA00090378 ACCEPT leaf (0) 0 yeast/LSM1 GO:0032991 protein-containing complex ARBA:ARBA00028902 KEEP_AS_NON_CORE very general (>200 descendants) 2083 yeast/MAD2 GO:0007094 mitotic spindle assembly checkpoint signaling ARBA:ARBA00044419 ACCEPT leaf (0) 0 yeast/MAD2 GO:0033597 mitotic checkpoint complex ARBA:ARBA00085107 ACCEPT specific (1-20) 1 yeast/MAD3 GO:0032991 protein-containing complex ARBA:ARBA00028902 MODIFY very general (>200 descendants) 2083 NEEDS_MORE_SPECIFIC true but uninformative replacement term The root term is uninformative. The complex Mad3 belongs to is precisely known and experimentally annotated (Mad2-Mad3-Bub3-Cdc20 mitotic checkpoint complex, GO:0033597, PMID:11726501, PMID:15879521), so the specific term should be used instead. yeast/MBP1 GO:0001228 DNA-binding transcription activator activity, RNA polymerase II-specific ARBA:ARBA00027759 ACCEPT leaf (0) 0 yeast/MBP1 GO:0030907 MBF transcription complex ARBA:ARBA00088331 ACCEPT leaf (0) 0 yeast/MCA1 GO:0004197 cysteine-type endopeptidase activity ARBA:ARBA00028064 ACCEPT specific (1-20) 4 yeast/MDM12 GO:0006869 lipid transport ARBA:ARBA00027046 ACCEPT general (21-200) 174 yeast/MDM12 GO:0012505 endomembrane system ARBA:ARBA00028953 KEEP_AS_NON_CORE very general (>200 descendants) 357 yeast/MDM34 GO:0006869 lipid transport ARBA:ARBA00027046 ACCEPT general (21-200) 174 yeast/MDM34 GO:0012505 endomembrane system ARBA:ARBA00028953 KEEP_AS_NON_CORE very general (>200 descendants) 357 yeast/MET16 GO:0006790 sulfur compound metabolic process ARBA:ARBA00028021 ACCEPT general (21-200) 190 yeast/MET2 GO:0006555 L-methionine metabolic process ARBA:ARBA00026499 KEEP_AS_NON_CORE specific (1-20) 8 yeast/MET3 GO:0006790 sulfur compound metabolic process ARBA:ARBA00028021 ACCEPT general (21-200) 190 yeast/MET5 GO:0000103 sulfate assimilation ARBA:ARBA00033980 ACCEPT specific (1-20) 1 yeast/MET5 GO:0009337 sulfite reductase complex (NADPH) ARBA:ARBA00092974 ACCEPT leaf (0) 0 yeast/MET6 GO:0071265 L-methionine biosynthetic process ARBA:ARBA00092883 ACCEPT specific (1-20) 5 yeast/MIS1 GO:0016874 ligase activity ARBA:ARBA00028597 MARK_AS_OVER_ANNOTATED very general (>200 descendants) 234 TOO_GENERAL true but uninformative Uninformative Uninformative parent of GO:0004329. yeast/MMM1 GO:0006869 lipid transport ARBA:ARBA00027046 ACCEPT general (21-200) 174 yeast/MMM1 GO:0012505 endomembrane system ARBA:ARBA00028953 ACCEPT very general (>200 descendants) 357 yeast/MNT4 GO:0000030 mannosyltransferase activity ARBA:ARBA00026934 KEEP_AS_NON_CORE general (21-200) 31 yeast/MNT4 GO:0005794 Golgi apparatus ARBA:ARBA00028708 KEEP_AS_NON_CORE general (21-200) 48 yeast/MPS1 GO:0000776 kinetochore ARBA:ARBA00027576 ACCEPT specific (1-20) 11 yeast/MPS1 GO:0098813 nuclear chromosome segregation ARBA:ARBA00027947 ACCEPT general (21-200) 80 yeast/MPS3 GO:0005635 nuclear envelope ARBA:ARBA00026328 ACCEPT general (21-200) 29 yeast/NAP1 GO:0005940 septin ring ARBA:ARBA00028521 KEEP_AS_NON_CORE specific (1-20) 8 yeast/NDI1 GO:0005739 mitochondrion ARBA:ARBA00026962 ACCEPT general (21-200) 70 yeast/NDI1 GO:0015980 energy derivation by oxidation of organic compounds ARBA:ARBA00026991 ACCEPT general (21-200) 76 yeast/NIT1 GO:0000257 nitrilase activity ARBA:ARBA00028522 MARK_AS_OVER_ANNOTATED specific (1-20) 6 UNCLASSIFIED unclassified "Not wrong at the branch level (branch 1 is the nitrilase branch and yeast NIT1 is placed there), but over-annotated: no nitrilase substrate is demonstrated for this protein, the gene is described as frequently inactivated and appears truncated, and nitrilase-superfamily database annotations are frequently applied without activity data. A specific ""nitrilase activity"" assertion is stronger than the evidence supports." yeast/NIT1 GO:0016836 hydro-lyase activity ARBA:ARBA00026984 REMOVE general (21-200) 120 WRONG_ACTIVITY wrong manual WRONG_ACTIVITY Wrong enzyme class: the carbon-nitrogen hydrolase superfamily hydrolyzes C-N bonds; hydro-lyase (EC 4.2.1.-, C-O lyase) activity is a different catalytic mechanism unsupported by the fold or the conserved triad. This is a spurious ARBA electronic mapping. yeast/NTE1 GO:0046486 glycerolipid metabolic process ARBA:ARBA00028375 MARK_AS_OVER_ANNOTATED general (21-200) 77 TOO_GENERAL true but uninformative general Over-general parent superseded by the specific PC metabolic terms already annotated. yeast/NTE1 GO:0004620 glycerophospholipase activity ARBA:ARBA00028545 MARK_AS_OVER_ANNOTATED general (21-200) 21 TOO_GENERAL true but uninformative broad This broad ARBA-inferred molecular-function parent is covered by the experimentally supported PC lysophospholipase/B-type phospholipase activities. yeast/NTE1 GO:0016020 membrane ARBA:ARBA00028763 MARK_AS_OVER_ANNOTATED very general (>200 descendants) 895 TOO_GENERAL true but uninformative root NTE1 is specifically an endoplasmic-reticulum membrane lipase; adding the root membrane term from ARBA loses the important compartmental specificity. yeast/NTE1 GO:0052689 carboxylic ester hydrolase activity ARBA:ARBA00028109 MARK_AS_OVER_ANNOTATED general (21-200) 122 TOO_GENERAL true but uninformative broad The ARBA molecular-function row is an over-broad hydrolase parent; NTE1 already carries experimentally supported, substrate-specific phospholipase terms. yeast/NUC1 GO:0004520 DNA endonuclease activity ARBA:ARBA00029205 ACCEPT general (21-200) 28 yeast/NUC1 GO:0004540 RNA nuclease activity ARBA:ARBA00027859 ACCEPT general (21-200) 41 yeast/NUC1 GO:0005739 mitochondrion ARBA:ARBA00026962 KEEP_AS_NON_CORE general (21-200) 70 yeast/NUC1 GO:0016788 hydrolase activity, acting on ester bonds ARBA:ARBA00026277 MODIFY very general (>200 descendants) 484 OTHER_TERM different term needed replacement term Nucleases are phosphodiester hydrolases, but the ARBA term should be narrowed to the directly supported DNA and RNA nuclease activities. yeast/ORC1 GO:0003688 DNA replication origin binding ARBA:ARBA00027846 ACCEPT leaf (0) 0 yeast/ORC1 GO:0005694 chromosome ARBA:ARBA00026361 KEEP_AS_NON_CORE very general (>200 descendants) 204 yeast/PAP2 GO:0031499 TRAMP complex ARBA:ARBA00085882 ACCEPT leaf (0) 0 yeast/PAP2 GO:0034475 U4 snRNA 3'-end processing ARBA:ARBA00092747 ACCEPT leaf (0) 0 yeast/PAP2 GO:0071035 nuclear polyadenylation-dependent rRNA catabolic process ARBA:ARBA00090756 ACCEPT leaf (0) 0 yeast/PAP2 GO:0071036 nuclear polyadenylation-dependent snoRNA catabolic process ARBA:ARBA00090754 ACCEPT leaf (0) 0 yeast/PAP2 GO:0071037 nuclear polyadenylation-dependent snRNA catabolic process ARBA:ARBA00090753 ACCEPT leaf (0) 0 yeast/PAP2 GO:0071038 TRAMP-dependent tRNA surveillance pathway ARBA:ARBA00027023 ACCEPT leaf (0) 0 yeast/PAP2 GO:0071039 nuclear polyadenylation-dependent CUT catabolic process ARBA:ARBA00090757 ACCEPT leaf (0) 0 yeast/PAP2 GO:0071042 nuclear polyadenylation-dependent mRNA catabolic process ARBA:ARBA00090807 ACCEPT leaf (0) 0 yeast/PAP2 GO:0071044 histone mRNA catabolic process ARBA:ARBA00090803 ACCEPT specific (1-20) 1 yeast/PAP2 GO:0071051 poly(A)-dependent snoRNA 3'-end processing ARBA:ARBA00090788 ACCEPT leaf (0) 0 yeast/PBS2 GO:0032991 protein-containing complex ARBA:ARBA00028902 KEEP_AS_NON_CORE very general (>200 descendants) 2083 yeast/PBS2 GO:0038066 p38MAPK cascade ARBA:ARBA00088051 ACCEPT leaf (0) 0 yeast/PBS2 GO:0071470 cellular response to osmotic stress ARBA:ARBA00027118 ACCEPT specific (1-20) 19 yeast/PDI1 GO:0006457 protein folding ARBA:ARBA00027200 ACCEPT specific (1-20) 7 yeast/PDI1 GO:0015035 protein-disulfide reductase activity ARBA:ARBA00026550 ACCEPT specific (1-20) 4 yeast/PDI1 GO:0051082 unfolded protein binding ARBA:ARBA00027557 MARK_AS_OVER_ANNOTATED leaf (0) 0 TOO_GENERAL true but uninformative more specific Marked over-annotated because more specific terms capture the biology more accurately. yeast/PDX3 GO:0042816 vitamin B6 metabolic process ARBA:ARBA00027956 MODIFY specific (1-20) 13 NEEDS_MORE_SPECIFIC true but uninformative replacement term Too general. yeast/POF1 GO:0009165 nucleotide biosynthetic process ARBA:ARBA00027613 MODIFY general (21-200) 114 NEEDS_MORE_SPECIFIC true but uninformative replacement term ARBA mapping to nucleotide biosynthetic process; NAD+ is a dinucleotide so this is correct but vague; the specific process is NAD+ biosynthesis via salvage. yeast/PPH21 GO:0000082 G1/S transition of mitotic cell cycle ARBA:ARBA00028571 MARK_AS_OVER_ANNOTATED leaf (0) 0 INDIRECT_EFFECT overreach phenotype The rule recapitulates the SGD IGI annotation without adding evidence; as discussed for the IGI rows, the multicopy-suppression phenotype shows that excess PP2A can substitute for Sit4 at G1/S, not that Pph21 normally performs a G1/S step. The established cell-cycle functions of Pph21-containing holoenzymes are at mitotic entry and exit. yeast/PPH21 GO:0000159 protein phosphatase type 2A complex ARBA:ARBA00090438 ACCEPT leaf (0) 0 yeast/PPH21 GO:0006417 regulation of translation ARBA:ARBA00027123 MARK_AS_OVER_ANNOTATED general (21-200) 122 INDIRECT_EFFECT overreach downstream The only route from Pph21 to translation is its membership of the Tap42-phosphatase complex downstream of TORC1; no direct translational substrate of Pph21 is known in yeast, and the TORC1 outputs that require Pph21/22 experimentally are transcriptional (NDP genes) and autophagic (Atg13). The term over-interprets pathway membership; it is retained as non-core rather than removed because it is not contradicted. yeast/PPH21 GO:1903432 regulation of TORC1 signaling ARBA:ARBA00027049 MODIFY specific (1-20) 2 TOO_SPECIFIC overreach replacement term The direction is off. The experimental evidence places Pph21/22 downstream of TORC1 as an effector phosphatase that is inhibited by TORC1 (via Tap42) and transduces the TORC1-inactivation signal (NDP gene induction, Atg13 dephosphorylation); it does not show Pph21 modulating TORC1 activity itself. The appropriate term is participation in TORC1 signalling rather than its regulation. yeast/PPH21 GO:2000786 positive regulation of autophagosome assembly ARBA:ARBA00085986 ACCEPT leaf (0) 0 yeast/RAD27 GO:0006281 DNA repair ARBA:ARBA00029008 ACCEPT general (21-200) 74 yeast/RAS2 GO:0097271 protein localization to bud neck ARBA:ARBA00089788 REMOVE leaf (0) 0 TOO_SPECIFIC overreach manual TOO_SPECIFIC IEA annotation for specific subcellular localization is overly detailed for computational inference. Specific experimental evidence (IGI) already provided. yeast/RIB1 GO:0003824 catalytic activity ARBA:ARBA00027533 MODIFY very general (>200 descendants) 6405 NEEDS_MORE_SPECIFIC true but uninformative replacement term ARBA rule yielding the root 'catalytic activity'; uninformative. Replace with GTP cyclohydrolase II activity. yeast/RIB2 GO:0016814 hydrolase activity, acting on carbon-nitrogen (but not peptide) bonds, in cyclic amidines ARBA:ARBA00026853 MODIFY general (21-200) 42 NEEDS_MORE_SPECIFIC true but uninformative replacement term ARBA assigns the EC 3.5.4 class (hydrolase acting on C-N bonds in cyclic amidines), the parent class of the pyrimidine deaminase. Correct but uninformative; the specific deaminase activity is already annotated. yeast/RIB2 GO:0019239 deaminase activity ARBA:ARBA00028263 MODIFY general (21-200) 39 NEEDS_MORE_SPECIFIC true but uninformative replacement term ARBA generic deaminase activity; correct parent of the riboflavin-pathway deaminase. yeast/RIB2 GO:0031119 tRNA pseudouridine synthesis ARBA:ARBA00026724 ACCEPT specific (1-20) 1 yeast/RIB7 GO:0016616 oxidoreductase activity, acting on the CH-OH group of donors, NAD or NADP as acceptor ARBA:ARBA00028442 MODIFY very general (>200 descendants) 364 NEEDS_MORE_SPECIFIC true but uninformative replacement term ARBA-predicted CH-OH/NAD(P) oxidoreductase activity. True for Rib7 (it oxidises/reduces the ribityl C1' alcohol with NAD(P)) but it is the direct parent of the more informative GO:0008703, which Rib7 already carries. yeast/RIM15 GO:0006950 response to stress ARBA:ARBA00026300 ACCEPT very general (>200 descendants) 590 yeast/RIM15 GO:1901992 positive regulation of mitotic cell cycle phase transition ARBA:ARBA00029089 KEEP_AS_NON_CORE specific (1-20) 8 yeast/RPD3 GO:0006355 regulation of DNA-templated transcription ARBA:ARBA00028138 ACCEPT general (21-200) 140 yeast/RPD3 GO:0010557 positive regulation of macromolecule biosynthetic process ACCEPT very general (>200 descendants) 270 yeast/RPD3 GO:0032221 Rpd3S complex ARBA:ARBA00085004 ACCEPT leaf (0) 0 yeast/RPD3 GO:0033698 Rpd3L complex ARBA:ARBA00084737 ACCEPT leaf (0) 0 yeast/RPD3 GO:0051052 regulation of DNA metabolic process ARBA:ARBA00027282 KEEP_AS_NON_CORE general (21-200) 185 yeast/SAM1 GO:0006555 L-methionine metabolic process ARBA:ARBA00026499 ACCEPT specific (1-20) 8 yeast/SAM2 GO:0006555 L-methionine metabolic process ARBA:ARBA00026499 KEEP_AS_NON_CORE specific (1-20) 8 yeast/SAS2 GO:0010468 regulation of gene expression ARBA:ARBA00028334 MARK_AS_OVER_ANNOTATED very general (>200 descendants) 874 TOO_GENERAL true but uninformative broad GO:0010468 is overly broad and abstract. SAS2s known roles are more specifically: (1) subtelomeric heterochromatin formation (GO:0031509), (2) silent mating-type cassette heterochromatin formation (GO:0030466), and (3) transcription regulation via histone modification. The more specific terms (GO:0031509, GO:0030466) should be preferred. yeast/SAS3 GO:0031507 heterochromatin formation ARBA:ARBA00033536 KEEP_AS_NON_CORE general (21-200) 25 yeast/SAS3 GO:0070775 H3 histone acetyltransferase complex ARBA:ARBA00084418 ACCEPT specific (1-20) 7 yeast/SER33 GO:0006564 L-serine biosynthetic process ARBA:ARBA00093701 ACCEPT leaf (0) 0 yeast/SET1 GO:0045944 positive regulation of transcription by RNA polymerase II ARBA:ARBA00027996 ACCEPT specific (1-20) 12 yeast/SET1 GO:0006325 chromatin organization ARBA:ARBA00028060 ACCEPT very general (>200 descendants) 290 yeast/SET1 GO:0008168 methyltransferase activity ARBA:ARBA00028302 KEEP_AS_NON_CORE very general (>200 descendants) 376 yeast/SIR2 GO:0000785 chromatin ARBA:ARBA00027601 ACCEPT general (21-200) 86 yeast/SIR2 GO:0017136 histone deacetylase activity, NAD-dependent ARBA:ARBA00027379 ACCEPT specific (1-20) 6 yeast/SIR2 GO:0030466 silent mating-type cassette heterochromatin formation ARBA:ARBA00087185 ACCEPT specific (1-20) 1 yeast/SIR2 GO:0031981 nuclear lumen ARBA:ARBA00026536 ACCEPT general (21-200) 139 yeast/SIR2 GO:0045910 negative regulation of DNA recombination ARBA:ARBA00086129 ACCEPT specific (1-20) 15 yeast/SIR3 GO:0005694 chromosome ARBA:ARBA00026361 ACCEPT very general (>200 descendants) 204 yeast/SIZ1 GO:0005694 chromosome ARBA:ARBA00026361 ACCEPT very general (>200 descendants) 204 yeast/SIZ1 GO:0007059 chromosome segregation ARBA:ARBA00026830 KEEP_AS_NON_CORE general (21-200) 86 yeast/SIZ1 GO:0019789 SUMO transferase activity ARBA:ARBA00027358 ACCEPT specific (1-20) 3 yeast/SIZ1 GO:1990683 DNA double-strand break attachment to nuclear envelope ARBA:ARBA00088737 KEEP_AS_NON_CORE leaf (0) 0 yeast/SLN1 GO:0007234 osmosensory signaling via phosphorelay pathway ARBA:ARBA00084941 ACCEPT leaf (0) 0 yeast/SLN1 GO:0140299 molecular sensor activity ARBA:ARBA00026335 ACCEPT general (21-200) 27 yeast/SNO1 GO:0008614 pyridoxine metabolic process ARBA:ARBA00084501 MODIFY specific (1-20) 1 OTHER_TERM different term needed replacement term As above. yeast/SNO2 GO:0008614 pyridoxine metabolic process ARBA:ARBA00084501 MODIFY specific (1-20) 1 OTHER_TERM different term needed replacement term Duplicate of the pyridoxine metabolic process annotation, from the ARBA machine-learning pipeline. It has the same legacy pyridoxine-specific scope problem as the IBA row; the correct family process is de novo PLP/vitamin B6 biosynthesis rather than pyridoxine metabolism. yeast/SNZ1 GO:0008615 pyridoxine biosynthetic process ARBA:ARBA00084504 MODIFY leaf (0) 0 OTHER_TERM different term needed replacement term Replace with de novo PLP biosynthesis. yeast/SOD2 GO:0005739 mitochondrion ARBA:ARBA00026962 ACCEPT general (21-200) 70 yeast/SPA2 GO:0030427 site of polarized growth ARBA:ARBA00045039 KEEP_AS_NON_CORE general (21-200) 38 yeast/SPA2 GO:0051286 cell tip ARBA:ARBA00089322 REMOVE specific (1-20) 20 WRONG_TAXON wrong manual WRONG_TAXON This ARBA row mirrors the fission-yeast-style cell-tip transfer rejected for the PomBase-derived PAINT rows rather than adding a budding-yeast compartment. The current UniProt record no longer has the generic Cell tip SubCell line that drove the retired UniProt row, and PMID:2647769 supports the broader GO:0030427 site of polarized growth rather than GO:0051286 specifically. yeast/SPH1 GO:0030427 site of polarized growth ARBA:ARBA00045039 ACCEPT general (21-200) 38 yeast/SPR1 GO:0009277 fungal-type cell wall ARBA:ARBA00026912 MODIFY specific (1-20) 11 NEEDS_MORE_SPECIFIC true but uninformative replacement term The electronic prediction captures Spr1's wall localization, but the direct localization evidence places Spr1 in the specialized ascospore wall, which is the more precise component. yeast/SPT16 GO:0010468 regulation of gene expression KEEP_AS_NON_CORE very general (>200 descendants) 874 yeast/SPT16 GO:0034728 nucleosome organization ACCEPT specific (1-20) 2 yeast/SPT16 GO:0006366 transcription by RNA polymerase II ARBA:ARBA00028158 KEEP_AS_NON_CORE specific (1-20) 19 yeast/SPT16 GO:0040029 epigenetic regulation of gene expression ARBA:ARBA00033485 KEEP_AS_NON_CORE general (21-200) 44 yeast/SRP40 GO:0005730 nucleolus ARBA:ARBA00026953 ACCEPT general (21-200) 24 yeast/SSA1 GO:0000049 tRNA binding ARBA:ARBA00088809 KEEP_AS_NON_CORE specific (1-20) 4 yeast/SSA1 GO:0000329 fungal-type vacuole membrane ARBA:ARBA00043543 KEEP_AS_NON_CORE leaf (0) 0 yeast/SSA1 GO:0006457 protein folding ARBA:ARBA00027200 ACCEPT specific (1-20) 7 yeast/SSA1 GO:0006616 SRP-dependent cotranslational protein targeting to membrane, translocation ARBA:ARBA00087312 MODIFY leaf (0) 0 OTHER_TERM different term needed replacement term The cited SSA/Ydj1 evidence concerns post-translational precursor translocation rather than the SRP-dependent cotranslational route. The replacement captures the supported mechanism without making it core. yeast/SSA1 GO:0009277 fungal-type cell wall ARBA:ARBA00026912 KEEP_AS_NON_CORE specific (1-20) 11 yeast/SSA1 GO:0033554 cellular response to stress KEEP_AS_NON_CORE very general (>200 descendants) 285 yeast/SSA1 GO:0043161 proteasome-mediated ubiquitin-dependent protein catabolic process ARBA:ARBA00026940 KEEP_AS_NON_CORE specific (1-20) 13 yeast/SSA1 GO:0051082 unfolded protein binding MODIFY leaf (0) 0 OTHER_TERM different term needed replacement term GO:0051082 is obsolete. SSA1 binds unfolded proteins as part of its ATP-dependent chaperone cycle, not as a passive binding activity. The correct annotation is the already-present GO:0044183 (protein folding chaperone) or its child GO:0140662 (ATP-dependent protein folding chaperone). Since GO:0044183 is already annotated via IBA, this IEA annotation should be replaced. yeast/SSA1 GO:0051170 import into nucleus ARBA:ARBA00026529 ACCEPT specific (1-20) 8 yeast/SSA2 GO:0000049 tRNA binding ARBA:ARBA00088809 KEEP_AS_NON_CORE specific (1-20) 4 yeast/SSA2 GO:0000329 fungal-type vacuole membrane ARBA:ARBA00043543 KEEP_AS_NON_CORE leaf (0) 0 yeast/SSA2 GO:0006457 protein folding ARBA:ARBA00027200 ACCEPT specific (1-20) 7 yeast/SSA2 GO:0006616 SRP-dependent cotranslational protein targeting to membrane, translocation ARBA:ARBA00087312 MODIFY leaf (0) 0 OTHER_TERM different term needed replacement term The SSA/Ydj1 evidence concerns post-translational precursor translocation, not the SRP-dependent cotranslational route. The replacement captures the supported class-level mechanism without making it core. yeast/SSA2 GO:0009277 fungal-type cell wall ARBA:ARBA00026912 KEEP_AS_NON_CORE specific (1-20) 11 yeast/SSA2 GO:0033554 cellular response to stress KEEP_AS_NON_CORE very general (>200 descendants) 285 yeast/SSA2 GO:0043161 proteasome-mediated ubiquitin-dependent protein catabolic process ARBA:ARBA00026940 KEEP_AS_NON_CORE specific (1-20) 13 yeast/SSA2 GO:0051082 unfolded protein binding MODIFY leaf (0) 0 OTHER_TERM different term needed replacement term GO:0051082 is now formally obsolete. SSA2 binds unfolded proteins as part of its ATP-dependent chaperone cycle. The correct annotation is GO:0140662 (ATP-dependent protein folding chaperone) or the already-present GO:0044183 (protein folding chaperone). yeast/SSA2 GO:0051170 import into nucleus ARBA:ARBA00026529 KEEP_AS_NON_CORE specific (1-20) 8 yeast/SSA3 GO:0006457 protein folding ACCEPT specific (1-20) 7 yeast/SSA3 GO:0006616 SRP-dependent cotranslational protein targeting to membrane, translocation ARBA:ARBA00087312 MODIFY leaf (0) 0 OTHER_TERM different term needed replacement term The broad translocation role is supported, but the electronic annotation is over-specific about SRP dependence. Replace it with the corresponding post-translational targeting/translocation term. yeast/SSA3 GO:0051082 unfolded protein binding MODIFY leaf (0) 0 OTHER_TERM different term needed replacement term Falcon emphasizes ATP-dependent, ATPase-cycle-coupled substrate binding; GO:0140662 (ATP-dependent protein folding chaperone) captures this more precisely than the generic unfolded protein binding. yeast/SSA3 GO:0030163 protein catabolic process ARBA:ARBA00027403 KEEP_AS_NON_CORE general (21-200) 66 yeast/SSA4 GO:0006457 protein folding ACCEPT specific (1-20) 7 yeast/SSA4 GO:0006616 SRP-dependent cotranslational protein targeting to membrane, translocation ARBA:ARBA00087312 MODIFY leaf (0) 0 OTHER_TERM different term needed replacement term ARBA-inferred SRP-dependent cotranslational term is the wrong mechanism for yeast Ssa Hsp70, which mediates post-translational translocation. yeast/SSA4 GO:0051082 unfolded protein binding MODIFY leaf (0) 0 OTHER_TERM different term needed replacement term Unfolded protein binding is correct but is the binding component of the broader ATP-dependent chaperone activity; the protein folding chaperone term better captures the core enabled function. yeast/SSB1 GO:0000054 ribosomal subunit export from nucleus ARBA:ARBA00090246 KEEP_AS_NON_CORE specific (1-20) 2 yeast/SSB1 GO:0006364 rRNA processing ARBA:ARBA00028153 KEEP_AS_NON_CORE general (21-200) 60 yeast/SSB1 GO:0006450 regulation of translational fidelity ARBA:ARBA00027186 KEEP_AS_NON_CORE specific (1-20) 13 yeast/SSB1 GO:0006452 translational frameshifting ARBA:ARBA00085751 KEEP_AS_NON_CORE leaf (0) 0 yeast/SSB1 GO:0051083 'de novo' cotranslational protein folding ARBA:ARBA00088074 ACCEPT leaf (0) 0 yeast/SSB2 GO:0000054 ribosomal subunit export from nucleus ARBA:ARBA00090246 KEEP_AS_NON_CORE specific (1-20) 2 yeast/SSB2 GO:0006364 rRNA processing ARBA:ARBA00028153 KEEP_AS_NON_CORE general (21-200) 60 yeast/SSB2 GO:0006450 regulation of translational fidelity ARBA:ARBA00027186 KEEP_AS_NON_CORE specific (1-20) 13 yeast/SSB2 GO:0006452 translational frameshifting ARBA:ARBA00085751 KEEP_AS_NON_CORE leaf (0) 0 yeast/SSB2 GO:0051082 unfolded protein binding ARBA:ARBA00027557 MODIFY leaf (0) 0 OTHER_TERM different term needed replacement term Modify because GO:0051082 is obsolete, not because substrate binding lacks support. OLS directs curators to consider GO:0044183; Ssb2's ATP-dependent Hsp70 mechanism supports its child GO:0140662. yeast/SSB2 GO:0051083 'de novo' cotranslational protein folding ARBA:ARBA00088074 ACCEPT leaf (0) 0 yeast/SSK1 GO:0000156 phosphorelay response regulator activity ARBA:ARBA00090436 ACCEPT leaf (0) 0 yeast/SSK1 GO:0006950 response to stress ARBA:ARBA00026300 MODIFY very general (>200 descendants) 590 NEEDS_MORE_SPECIFIC true but uninformative replacement term Not wrong, but uninformative: the stress Ssk1 responds to is hyperosmotic, and it acts as the signalling input into the HOG osmostress pathway. The specific term cellular hyperosmotic response (GO:0071474) is already annotated experimentally and should be preferred. yeast/SSK1 GO:0071467 cellular response to pH ARBA:ARBA00092243 KEEP_AS_NON_CORE specific (1-20) 4 yeast/SSK2 GO:0038066 p38MAPK cascade ARBA:ARBA00088051 ACCEPT leaf (0) 0 yeast/SSK22 GO:0038066 p38MAPK cascade ARBA:ARBA00088051 ACCEPT leaf (0) 0 yeast/SSQ1 GO:0005739 mitochondrion ARBA:ARBA00026962 ACCEPT general (21-200) 70 yeast/SSQ1 GO:0070013 intracellular organelle lumen ARBA:ARBA00027917 ACCEPT very general (>200 descendants) 239 yeast/STE11 GO:0005737 cytoplasm ARBA:ARBA00026971 ACCEPT very general (>200 descendants) 1146 yeast/STE11 GO:0071507 pheromone response MAPK cascade ARBA:ARBA00092461 ACCEPT leaf (0) 0 yeast/STE7 GO:0051286 cell tip ARBA:ARBA00089322 ACCEPT specific (1-20) 20 yeast/STE7 GO:0071507 pheromone response MAPK cascade ARBA:ARBA00092461 ACCEPT leaf (0) 0 yeast/STR2 GO:0016765 transferase activity, transferring alkyl or aryl (other than methyl) groups ARBA:ARBA00026321 KEEP_AS_NON_CORE general (21-200) 102 yeast/STR2 GO:0050667 homocysteine metabolic process ARBA:ARBA00089512 KEEP_AS_NON_CORE specific (1-20) 4 yeast/SWE1 GO:0004713 protein tyrosine kinase activity ARBA:ARBA00027631 ACCEPT general (21-200) 22 yeast/SWE1 GO:0051447 negative regulation of meiotic cell cycle ARBA:ARBA00088857 ACCEPT general (21-200) 23 yeast/SWI2 GO:0140658 ATP-dependent chromatin remodeler activity ARBA:ARBA00085709 ACCEPT specific (1-20) 5 yeast/SWI2 GO:0140008 histone H4 reader activity ARBA:ARBA00084856 ACCEPT specific (1-20) 7 yeast/SWI2 GO:0045944 positive regulation of transcription by RNA polymerase II ARBA:ARBA00027996 ACCEPT specific (1-20) 12 yeast/SWI2 GO:0045815 transcription initiation-coupled chromatin remodeling ARBA:ARBA00086456 ACCEPT specific (1-20) 1 yeast/SWI2 GO:0006302 double-strand break repair ARBA:ARBA00027906 ACCEPT general (21-200) 28 yeast/SWI3 GO:0006338 chromatin remodeling ARBA:ARBA00027994 ACCEPT very general (>200 descendants) 235 yeast/SWI3 GO:0006355 regulation of DNA-templated transcription ARBA:ARBA00028138 ACCEPT general (21-200) 140 yeast/SWI4 GO:0001228 DNA-binding transcription activator activity, RNA polymerase II-specific ARBA:ARBA00027759 ACCEPT leaf (0) 0 yeast/SWI4 GO:0090575 RNA polymerase II transcription regulator complex ARBA:ARBA00028248 ACCEPT general (21-200) 44 yeast/SWI6 GO:0045944 positive regulation of transcription by RNA polymerase II ARBA:ARBA00027996 ACCEPT specific (1-20) 12 yeast/SWI6 GO:0090575 RNA polymerase II transcription regulator complex ARBA:ARBA00028248 ACCEPT general (21-200) 44 yeast/TCP1 GO:0005832 chaperonin-containing T-complex ARBA:ARBA00029273 ACCEPT leaf (0) 0 yeast/TEM1 GO:0005816 spindle pole body ARBA:ARBA00029126 ACCEPT specific (1-20) 18 yeast/TEM1 GO:0035556 intracellular signal transduction ARBA:ARBA00026887 ACCEPT general (21-200) 195 yeast/TEM1 GO:0090068 positive regulation of cell cycle process ARBA:ARBA00029176 ACCEPT general (21-200) 104 yeast/THI80 GO:0042723 thiamine-containing compound metabolic process ARBA:ARBA00028583 MODIFY specific (1-20) 12 NEEDS_MORE_SPECIFIC true but uninformative replacement term ARBA prediction of the very general thiamine-containing compound metabolic process. Correct but uninformative; the specific process is TPP biosynthesis. yeast/TIM10 GO:0042719 mitochondrial intermembrane space chaperone complex ARBA:ARBA00033589 ACCEPT leaf (0) 0 yeast/TIM10 GO:0045039 protein insertion into mitochondrial inner membrane ARBA:ARBA00029129 ACCEPT specific (1-20) 2 yeast/TIM9 GO:0042719 mitochondrial intermembrane space chaperone complex ACCEPT leaf (0) 0 yeast/TIM9 GO:0045039 protein insertion into mitochondrial inner membrane ARBA:ARBA00029129 ACCEPT specific (1-20) 2 yeast/TIM9 GO:0070013 intracellular organelle lumen ARBA:ARBA00027917 MODIFY very general (>200 descendants) 239 NEEDS_MORE_SPECIFIC true but uninformative replacement term TIM9 is an IMS protein, and GO:0070013 is an overly generic ancestor that loses the mitochondrial specificity established by direct and UniProt evidence. Use GO:0005758 mitochondrial intermembrane space instead. yeast/TOR1 GO:0000329 fungal-type vacuole membrane ARBA:ARBA00043543 ACCEPT leaf (0) 0 yeast/TOR1 GO:0006995 cellular response to nitrogen starvation ARBA:ARBA00034562 ACCEPT specific (1-20) 2 yeast/TOR1 GO:0010507 negative regulation of autophagy ARBA:ARBA00043537 ACCEPT specific (1-20) 10 yeast/TOR1 GO:0031929 TOR signaling ARBA:ARBA00086602 ACCEPT specific (1-20) 2 yeast/TOR1 GO:0031931 TORC1 complex ARBA:ARBA00026257 ACCEPT leaf (0) 0 yeast/TOR1 GO:0042254 ribosome biogenesis ARBA:ARBA00026817 ACCEPT general (21-200) 78 yeast/TOR1 GO:1905356 regulation of snRNA pseudouridine synthesis ARBA:ARBA00087228 KEEP_AS_NON_CORE specific (1-20) 2 yeast/TRX1 GO:0000011 vacuole inheritance ARBA:ARBA00088811 ACCEPT leaf (0) 0 yeast/TRX1 GO:0006888 endoplasmic reticulum to Golgi vesicle-mediated transport ARBA:ARBA00027177 KEEP_AS_NON_CORE specific (1-20) 6 yeast/TRX1 GO:0006890 retrograde vesicle-mediated transport, Golgi to endoplasmic reticulum ARBA:ARBA00086884 KEEP_AS_NON_CORE specific (1-20) 3 yeast/TRX1 GO:0042144 vacuole fusion, non-autophagic ARBA:ARBA00085976 ACCEPT leaf (0) 0 yeast/TRX1 GO:0045454 cell redox homeostasis ARBA:ARBA00085337 ACCEPT leaf (0) 0 yeast/TRX2 GO:0000011 vacuole inheritance ARBA:ARBA00088811 ACCEPT leaf (0) 0 yeast/TRX2 GO:0006888 endoplasmic reticulum to Golgi vesicle-mediated transport ARBA:ARBA00027177 KEEP_AS_NON_CORE specific (1-20) 6 yeast/TRX2 GO:0006890 retrograde vesicle-mediated transport, Golgi to endoplasmic reticulum ARBA:ARBA00086884 KEEP_AS_NON_CORE specific (1-20) 3 yeast/TRX2 GO:0042144 vacuole fusion, non-autophagic ARBA:ARBA00085976 ACCEPT leaf (0) 0 yeast/TRX2 GO:0045454 cell redox homeostasis ARBA:ARBA00085337 ACCEPT leaf (0) 0 yeast/TSA1 GO:0008379 thioredoxin peroxidase activity ARBA:ARBA00092050 ACCEPT leaf (0) 0 yeast/TSA1 GO:0034599 cellular response to oxidative stress ARBA:ARBA00027632 ACCEPT general (21-200) 25 yeast/TSA1 GO:0034605 cellular response to heat ARBA:ARBA00026567 KEEP_AS_NON_CORE specific (1-20) 3 yeast/TSA1 GO:0045454 cell redox homeostasis ARBA:ARBA00085337 ACCEPT leaf (0) 0 yeast/TSA1 GO:0050821 protein stabilization ARBA:ARBA00033884 KEEP_AS_NON_CORE leaf (0) 0 yeast/VPS45 GO:0005794 Golgi apparatus ARBA:ARBA00028708 ACCEPT general (21-200) 48 yeast/VPS45 GO:0006886 intracellular protein transport ARBA:ARBA00027179 ACCEPT general (21-200) 66 yeast/VPS45 GO:0031201 SNARE complex ARBA:ARBA00028851 MARK_AS_OVER_ANNOTATED specific (1-20) 18 UNCLASSIFIED unclassified Vps45p binds both individual SNAREs and assembled SNARE complexes, but it is an SM-family regulator rather than one of the SNARE proteins forming the core four-helix complex. SNARE binding and positive regulation of SNARE complex assembly capture the evidence without asserting membership. yeast/VPS45 GO:0031338 regulation of vesicle fusion ARBA:ARBA00086104 ACCEPT specific (1-20) 19 yeast/VPS45 GO:0098588 bounding membrane of organelle ARBA:ARBA00027281 ACCEPT very general (>200 descendants) 201 yeast/YDJ1 GO:0001671 ATPase activator activity ARBA:ARBA00089918 ACCEPT specific (1-20) 1 yeast/YDJ1 GO:0070585 protein localization to mitochondrion ARBA:ARBA00028355 ACCEPT specific (1-20) 7 yeast/YPD1 GO:0007234 osmosensory signaling via phosphorelay pathway ARBA:ARBA00084941 ACCEPT leaf (0) 0 yeast/YPD1 GO:0016772 transferase activity, transferring phosphorus-containing groups ARBA:ARBA00026261 MODIFY very general (>200 descendants) 567 NEEDS_MORE_SPECIFIC true but uninformative replacement term Correct but overly general; GO:0009927 histidine phosphotransfer kinase activity is the appropriate specific term for an HPt protein and is already supported by IBA and experimental data.