# Generated by summarize.py; do not edit by hand. # Every adjudicated claim judged wrong (NPI/PLI/REP), by GO aspect and error type. BP: MULTIPLE_FUNCTIONS: - claim_id: NAR-15 gene: SKP1 organism_dir: yeast term: GO:0010458 exit from mitosis category: NARROWER assessment: NPI rationale: Skp1 mutant mitotic arrest (short spindle, G2 DNA content) is attributed in the review to Skp1's CBF3 kinetochore role and SCF-driven G1/S and G2/M transitions; no evidence that Skp1 drives the M-to-G1 exit transition, so this looks like a phenotype-derived term from an ortholog's mitotic-arrest phenotype. - claim_id: REJ-13 gene: UCK2 organism_dir: human term: GO:0007631 feeding behavior category: REJECTED assessment: NPI rationale: UCK2 is a cytosolic pyrimidine-salvage uridine/cytidine kinase. 'Feeding behavior' is an organism-level phenotype term transferred from an ortholog and does not reflect any activity of the enzyme. The curator's removal is correct. - claim_id: UNR-05 gene: AAK1 organism_dir: human term: GO:0008356 asymmetric cell division category: UNRELATED assessment: NPI rationale: No evidence links human AAK1 to asymmetric cell division; the term likely derives from invertebrate Numb-associated kinase / Numb pathway phenotypes, whereas AAK1 acts as an AP-2 kinase in clathrin-mediated endocytosis and focal-adhesion turnover. - claim_id: UNR-22 gene: ssuD organism_dir: PSEPK term: GO:0009408 response to heat category: UNRELATED assessment: NPI rationale: SsuD is the FMNH2-dependent alkanesulfonate monooxygenase for sulfur scavenging, induced by sulfate limitation; nothing in the review or UniProt links it to heat stress, so the term is likely an expression or phenotype-derived transfer from a bacterial ortholog. - claim_id: UNR-01 gene: HSC82 organism_dir: yeast term: GO:0044182 filamentous growth of a population of unicellular organisms category: UNRELATED assessment: NPI rationale: Likely transferred from Candida albicans Hsp90, whose role in filamentation (Hsp90 restrains the yeast-to-hypha transition) is a client-dependent phenotype. There is no evidence for Hsc82 in S. cerevisiae pseudohyphal growth; its core role is the ATP-dependent Hsp90 chaperone cycle. - claim_id: UNR-10 gene: cryaba organism_dir: DANRE term: GO:0032355 response to estradiol category: UNRELATED assessment: NPI rationale: Response to estradiol is an expression-response term from a mammalian CRYAB ortholog. Zebrafish cryaba is a subfunctionalized, lens-restricted crystallin with no evidence of estradiol responsiveness. - claim_id: R2-BP-NAR-06 gene: tbx5b organism_dir: DANRE term: GO:0060039 pericardium development category: NARROWER assessment: NPI rationale: tbx5b loss causes failed cardiac looping and a fluid-filled edema around the heart, a non-specific consequence of heart dysfunction rather than a defect in development of the pericardial sac; the term is a phenotype-derived transfer (likely from tbx5a/Tbx5 pericardial edema phenotypes). - claim_id: R2-BP-UNR-09 gene: hlh-30 organism_dir: worm term: GO:0045165 cell fate commitment category: UNRELATED assessment: NPI rationale: HLH-30 is the TFEB ortholog and regulates transcription of autophagy, lysosomal and lipid-metabolism genes. Cell fate commitment is a vertebrate MiT/TFE developmental term (e.g. MITF in melanocyte and RPE specification) that has no counterpart in worm hlh-30 biology. - claim_id: R2-BP-UNR-03 gene: Pde4 organism_dir: DROME term: GO:0040013 negative regulation of locomotion category: UNRELATED assessment: NPI rationale: Locomotor phenotype term likely transferred from a mammalian PDE4 mutant phenotype; Pde4/dunce is a cAMP phosphodiesterase whose behavioural effects are downstream of cAMP turnover in specific circuits. No fly evidence that dunce negatively regulates locomotion. TAXON_CONSTRAINT_VIOLATION: - claim_id: UNR-39 gene: ced-6 organism_dir: worm term: GO:0016319 mushroom body development category: UNRELATED assessment: NPI rationale: Mushroom bodies are an insect brain structure; the term comes from a Drosophila Ced-6 mutant phenotype. C. elegans has no mushroom body, and CED-6 acts as a PTB adaptor downstream of CED-1 in apoptotic-corpse engulfment. - claim_id: UNR-04 gene: dyf-6 organism_dir: worm term: GO:0060041 retina development in camera-type eye category: UNRELATED assessment: NPI rationale: Camera-type eye/retina development comes from a vertebrate ift46 mutant phenotype (photoreceptor cilia). C. elegans has no camera-type eye; DYF-6/IFT46 acts in IFT-B in amphid/phasmid sensory cilia. - claim_id: UNR-11 gene: HST2 organism_dir: yeast term: GO:0036166 phenotypic switching category: UNRELATED assessment: NPI rationale: Phenotypic switching (e.g. white-opaque switching) is a Candida albicans trait in which sirtuins have been implicated. S. cerevisiae does not show this switching. HST2 is an NAD-dependent H4K16 deacetylase that acts in chromatin regulation. - claim_id: UNR-08 gene: elg1 organism_dir: DROME term: GO:0030890 positive regulation of B cell proliferation category: UNRELATED assessment: NPI rationale: Drosophila has no B cells; this vertebrate immune process term was transferred from ATAD5/Elg1 orthologs (likely a mouse phenotype) and cannot apply to the fly protein, which acts as the PCNA unloader subunit. - claim_id: UNR-40 gene: drd-5 organism_dir: CAEBR term: GO:0007601 visual perception category: UNRELATED assessment: NPI rationale: drd-5 is an uncharacterized nematode SDR whose closest characterized ortholog (DHS-16) acts in dafachronic acid steroid synthesis; visual perception comes from vertebrate retinol dehydrogenase SDRs of the visual cycle, a process nematodes (no eyes or retinoid visual cycle) lack. - claim_id: R2-BP-REJ-06 gene: Gcm organism_dir: STRPU term: GO:0007403 glial cell fate determination category: REJECTED assessment: NPI rationale: Glial fate determination is a Drosophila-specific use of gcm. Sea urchin Gcm is expressed only in the mesodermal pigment-cell lineage and is never seen in neural or glial tissue, and its knockdown removes pigment cells. The curator's removal of the parent gliogenesis term is well supported. - claim_id: R2-BP-NAR-01 gene: mre11 organism_dir: DROME term: GO:0007004 telomere maintenance via telomerase category: NARROWER assessment: NPI rationale: Drosophila lacks telomerase and maintains telomere length by HeT-A/TART retrotransposition; fly Mre11 acts in telomere capping (HOAP/HP1 recruitment, fusion prevention), not telomerase-mediated repeat addition. The telomerase-specific child of telomere maintenance was transferred from yeast/mammalian MRE11 where telomerase exists. - claim_id: R2-BP-REJ-03 gene: smo organism_dir: DROME term: GO:0071679 commissural neuron axon guidance category: REJECTED assessment: NPI rationale: Shh/Smo-mediated chemoattraction of commissural axons is a vertebrate spinal-cord mechanism. No such Hh/Smo role in commissural guidance is described in Drosophila, and fly smo is not among the PAINT donors. The curator's removal of this over-deep IBA stands. - claim_id: R2-BP-UNR-12 gene: alc organism_dir: DROME term: GO:0035878 nail development category: UNRELATED assessment: NPI rationale: Nail development is a mammalian (digit keratinized appendage) process, presumably transferred from a mouse AMPK beta-subunit phenotype; Drosophila has no nails. alc is the AMPK beta scaffold acting in energy sensing and photoreceptor/neuron maintenance. CURATION_MISTAKE: - claim_id: REJ-02 gene: BNIP3L organism_dir: human term: GO:0051607 defense response to virus category: REJECTED assessment: NPI rationale: 'Curator removed defense response to virus: the source 1999 paper concerns apoptosis/BCL-2 interactions, and later work shows NIX-mediated mitophagy is hijacked by SARS-CoV-2 ORF10 to degrade MAVS, i.e. viral immune evasion rather than host antiviral defense. Transferring the same unsupported ortholog annotation does not add evidence.' - claim_id: REJ-04 gene: Mapk1 organism_dir: rat term: GO:0019858 cytosine metabolic process category: REJECTED assessment: NPI rationale: ERK2 is a protein kinase with no role executing cytosine metabolism; the donor mouse annotation misapplies a process term from an IDA paper, and the curator removed the same term for this reason. - claim_id: UNR-15 gene: Dnajb11 organism_dir: mouse term: GO:0036498 IRE1-mediated unfolded protein response category: UNRELATED assessment: NPI rationale: ERdj3 is an ER-lumenal BiP co-chaperone whose gene is induced by IRE1/XBP1s; being a UPR target gene is not participation in IRE1-mediated signaling, so the term (likely from Reactome target-gene membership) does not describe its function. - claim_id: UNR-16 gene: Rbpj organism_dir: mouse term: GO:0006310 DNA recombination category: UNRELATED assessment: NPI rationale: RBP-J was named 'recombination signal binding protein for Ig kappa J' because it was first thought to bind V(D)J recombination signals. It was later shown to be the CSL transcription factor of Notch signalling with no recombinase role, so DNA recombination is a historical name-based error. - claim_id: R2-BP-REJ-02 gene: App organism_dir: mouse term: GO:0006468 protein phosphorylation category: REJECTED assessment: NPI rationale: APP has no kinase domain or kinase activity; the source IMP (PMID:16025111) actually describes Abeta-triggered DEPHOSPHORYLATION of NR2B by PP2B/STEP, so the ortholog annotation being transferred was itself a misreading. The curator's removal stands. - claim_id: R2-BP-REJ-05 gene: SPCS3 organism_dir: human term: GO:0045047 protein targeting to ER category: REJECTED assessment: NPI rationale: SPCS3 is a non-catalytic accessory subunit of the ER signal peptidase complex, which cleaves signal peptides from substrates already being translocated; it acts downstream of, and does not direct, ER targeting (SRP/SRP receptor/Sec61 do). The source PANTHER-level term mis-specifies signal-peptide processing as targeting. - claim_id: R2-BP-UNR-07 gene: ndx-1 organism_dir: worm term: GO:0046712 GDP catabolic process category: UNRELATED assessment: NPI rationale: NDX-1 is an 8-oxo-(d)GDP phosphatase that sanitises oxidised guanine nucleotides; purified NDX-1 hydrolyses unoxidised GDP at under 5% and does not act on dGDP. GDP catabolism conflates the oxidised substrate with ordinary GDP and implies a role in normal GDP turnover that is not supported. - claim_id: R2-BP-REJ-01 gene: D14 organism_dir: ARATH term: GO:1901601 strigolactone biosynthetic process category: REJECTED assessment: NPI rationale: D14 is the strigolactone receptor and D-ring hydrolase acting downstream of SL synthesis. d14 mutants are SL-insensitive and over-accumulate SL rather than lacking it, a feedback effect, and the biosynthetic steps are performed by D27, CCD7, CCD8 and MAX1. The source IBA/IMP annotations are themselves wrong, and the removal stands. FREQUENCY_BIAS: - claim_id: UNR-17 gene: ALDH4A1 organism_dir: human term: GO:0007165 signal transduction category: UNRELATED assessment: REP rationale: ALDH4A1 is a mitochondrial delta-1-pyrroline-5-carboxylate dehydrogenase in proline catabolism; generic 'signal transduction' has no specific basis for this enzyme and reflects a high-frequency ortholog term. - claim_id: R2-BP-UNR-02 gene: cebp-2 organism_dir: worm term: GO:0016071 mRNA metabolic process category: UNRELATED assessment: NPI rationale: CEBP-2 is a bZIP transcription factor regulating immune and lipid-metabolism genes; there is no evidence it participates in mRNA processing, stability or degradation. Regulating transcription of target genes is not mRNA metabolism. IN_VITRO_NOT_IN_VIVO: - claim_id: REJ-14 gene: Hspa8 organism_dir: rat term: GO:0046777 protein autophosphorylation category: REJECTED assessment: NPI rationale: The review removed this term because the cited paper reports HSC70 ATPase activity, not autophosphorylation. Reports of Hsp70 'autophosphorylation' are in vitro phospho-intermediate observations with no established physiological role; HSC70's function is ATP-dependent chaperoning. PATHWAY_CONTEXT_IGNORED: - claim_id: UNR-07 gene: ddb-1 organism_dir: worm term: GO:0051702 biological process involved in interaction with symbiont category: UNRELATED assessment: NPI rationale: DDB1 symbiont-interaction annotations come from viral proteins (e.g. HBx, paramyxovirus V) hijacking human or plant CRL4-DDB1. Worm DDB-1 is a CRL4 adaptor with no evidence of symbiont or viral interaction, so the host-pathogen context does not carry over. CC: CURATION_MISTAKE: - claim_id: UNR-12 gene: rad21 organism_dir: SCHPO term: GO:0005739 mitochondrion category: UNRELATED assessment: NPI rationale: Rad21 is the nuclear alpha-kleisin of mitotic cohesin with extensive nuclear/chromatin evidence and no mitochondrial targeting or function; a mitochondrion transfer most likely reflects a high-throughput localization artefact in an ortholog. - claim_id: UNR-30 gene: Amacr organism_dir: rat term: GO:0005886 plasma membrane category: UNRELATED assessment: NPI rationale: Amacr is a peroxisomal and mitochondrial matrix racemase with no membrane-targeting features; plasma membrane has no support for the rat protein and likely reflects a proteomics/localization artefact in an ortholog. - claim_id: UNR-19 gene: Egf organism_dir: mouse term: GO:0043235 signaling receptor complex category: UNRELATED assessment: NPI rationale: EGF is the secreted ligand that binds EGFR, not a component of the receptor complex. GO defines a signaling receptor complex as the complex that binds the signaling molecule, so a ligand-to-receptor-complex transfer conflates bound ligand with complex membership. - claim_id: R2-CC-UNR-09 gene: Gcat organism_dir: DROME term: GO:0005886 plasma membrane category: UNRELATED assessment: NPI rationale: Gcat is a mitochondrial-matrix PLP enzyme of threonine catabolism with no transmembrane segment or membrane anchor. A plasma membrane location is unsupported for it and is most likely a high-throughput localization artifact on an ortholog. - claim_id: R2-CC-REJ-02 gene: nudE organism_dir: DROME term: GO:0005871 kinesin complex category: REJECTED assessment: NPI rationale: NudE is a Lis1/dynein regulator, not a kinesin subunit; the family-level kinesin complex IBA stems from rat Ndel1 being reported as a kinesin-1 cargo, and was removed in the human NDE1/NDEL1 reviews. No fly evidence links NudE to a kinesin complex, so the removal stands. - claim_id: R2-CC-REJ-04 gene: nudE organism_dir: EMENI term: GO:0005871 kinesin complex category: REJECTED assessment: NPI rationale: A. nidulans NudE supports NudF/LIS1-dependent dynein activation and is not a kinesin complex subunit; the IBA derives from rat Ndel1 described as a kinesin-1 cargo. No fungal evidence supports kinesin complex membership. - claim_id: R2-CC-NAR-06 gene: Acadvl organism_dir: DROME term: GO:0042645 mitochondrial nucleoid category: NARROWER assessment: NPI rationale: Acadvl is a mitochondrial inner-membrane-associated beta-oxidation flavoenzyme; mitochondrial nucleoid assignments for VLCAD-family proteins come from nucleoid-preparation proteomics, which co-purify inner-membrane proteins. No evidence that the fly enzyme is a nucleoid component. TAXON_CONSTRAINT_VIOLATION: - claim_id: NAR-05 gene: HRT1 organism_dir: yeast term: GO:0031467 Cul7-RING ubiquitin ligase complex category: NARROWER assessment: NPI rationale: Cul7 (and the Cul7-RING ligase) is metazoan-specific and absent from S. cerevisiae; yeast Hrt1/Rbx1 is in SCF, Cul3 and Cul4/Rtt101 cullin-RING complexes, not a Cul7 complex. Transfer from metazoan RBX1 ignores lineage. - claim_id: NAR-07 gene: unc-47 organism_dir: worm term: GO:0044316 cone cell pedicle category: NARROWER assessment: NPI rationale: Cone cell pedicle is a vertebrate retinal cone axon terminal; C. elegans has no cone photoreceptors, so this transfer from vertebrate VGAT (SLC32A1) retinal data cannot apply to UNC-47. - claim_id: R2-CC-UNR-08 gene: che-11 organism_dir: worm term: GO:0005813 centrosome category: UNRELATED assessment: NPI rationale: Human IFT140 has an IDA for centrosome in cycling mammalian cells, but CHE-11 acts only in post-mitotic C. elegans ciliated sensory neurons. There the centrioles degenerate after ciliogenesis and no centrosome is present. Its ciliary-base location is already captured by ciliary basal body, axoneme and non-motile cilium. - claim_id: R2-CC-UNR-03 gene: Ccnt1 organism_dir: mouse term: GO:0005703 polytene chromosome puff category: UNRELATED assessment: NPI rationale: Polytene chromosome puffs exist only in dipteran polytene tissues; mouse has no polytene chromosomes. The term was transferred from the Drosophila CycT ortholog's immunostaining; mouse cyclin T1 is in nucleoplasmic P-TEFb. LOCALIZATION_DEFAULT: - claim_id: UNR-20 gene: Myd88 organism_dir: DROME term: GO:0005829 cytosol category: UNRELATED assessment: NPI rationale: Mammalian MyD88 is a cytosolic adaptor, but Drosophila Myd88 is held at the plasma membrane by its PI(4,5)P2-binding C-terminal extension (cytoplasmic side of plasma membrane, IDA); the cytosol transfer from vertebrate orthologs ignores this fly-specific membrane targeting. - claim_id: R2-CC-UNR-06 gene: Sstr5 organism_dir: rat term: GO:0005737 cytoplasm category: UNRELATED assessment: NPI rationale: 'SSTR5 is a multi-pass plasma-membrane GPCR (UniProt: Cell membrane); the review supports only plasma membrane and neuron projection. Bulk ''cytoplasm'' is a default compartment with no specific basis; any intracellular pool would be internalized receptor on endosome membranes, not the cytoplasm.' - claim_id: R2-CC-UNR-07 gene: DARS2 organism_dir: HORSE term: GO:0005634 nucleus category: UNRELATED assessment: NPI rationale: DARS2 is the mitochondrial aspartyl-tRNA synthetase with an N-terminal mitochondrial targeting sequence acting on mt-tRNA(Asp); no nuclear role or localization is reported (human DARS2 has no nucleus annotation), so nucleus is a generic default localization (possibly bleeding from the cytosolic DARS1 paralog, which has a nuclear pool). - claim_id: R2-CC-REJ-01 gene: pef-1 organism_dir: worm term: GO:0005634 nucleus category: REJECTED assessment: NPI rationale: PEF-1 is anchored to membranes by N-terminal myristoylation and palmitoylation. Both localization studies place it in sensory cilia, the plasma membrane and neuronal processes, never in the nucleus. The nucleus IBA, and its eggNOG echo, is a family-level default that does not fit this membrane-anchored ciliary phosphatase; the curator's removal stands. PARALOG_OVERANNOTATION: - claim_id: NAR-10 gene: SWI3 organism_dir: yeast term: GO:0016586 RSC-type complex category: NARROWER assessment: PLI rationale: In S. cerevisiae Swi3 is a SWI/SNF subunit; the RSC complex uses its paralog Rsc8/Swh3. The RSC-type term likely comes from metazoan SMARCC1/2 (shared by BAF and PBAF), which does not hold for the yeast paralog split. - claim_id: UNR-36 gene: Ang2 organism_dir: mouse term: GO:0043025 neuronal cell body category: UNRELATED assessment: PLI rationale: The neuronal cell body localization comes from canonical angiogenin (ANG/Ang1) neural biology. Ang2/Angrp is a secreted, divergent non-angiogenic RNase A paralog, and the review removes the whole set of canonical-angiogenin intracellular transfers. FREQUENCY_BIAS: - claim_id: UNR-09 gene: mdr organism_dir: STABO term: GO:0000324 fungal-type vacuole category: UNRELATED assessment: NPI rationale: Mdr is a full-length ABCB/MDR-subfamily exporter that secretes sophorolipids, and UniProt and the transportome analysis place it in the plasma membrane. Nothing supports vacuolar localization. The term looks like a common fungal localization carried over from orthologs, not specific evidence. DOMAIN_ARCHITECTURE_MISMATCH: - claim_id: R2-CC-REJ-03 gene: Idh organism_dir: DROME term: GO:0005782 peroxisomal matrix category: REJECTED assessment: NPI rationale: Peroxisomal matrix localization of the donor IDH1/IDP3 enzymes depends on a C-terminal PTS1; every fly Idh isoform (incl. B7Z0E0) ends in ...AVAAK with no PTS1 and fly Idh is documented as cytosolic (IDHc) or mitochondrial (IDHm). The single fly gene is co-orthologous to IDH1 and IDH2, so the IDH1-clade peroxisomal targeting was transferred without the targeting signal that confers it. MF: CURATION_MISTAKE: - claim_id: REJ-19 gene: Txn1 organism_dir: mouse term: GO:0004791 thioredoxin-disulfide reductase (NADPH) activity category: REJECTED assessment: NPI rationale: Thioredoxin is the substrate of thioredoxin reductase (TXNRD), not an NADPH-using reductase itself; the review removed the related NAD(P)H-dependent reductase term for exactly this reason. The predicted activity belongs to the partner enzyme Txnrd1/2. - claim_id: REJ-17 gene: Ratn1 organism_dir: rat term: GO:0005009 insulin receptor activity category: REJECTED assessment: NPI rationale: Rat n 1 is a secreted ~19 kDa lipocalin with no transmembrane or tyrosine-kinase domain, so it cannot have insulin receptor activity. The source mouse MUP1 annotation is itself contradicted by its own study (no change in insulin receptor phosphorylation). The curator's removal is correct. - claim_id: UNR-23 gene: Kras organism_dir: mouse term: GO:0005085 guanyl-nucleotide exchange factor activity category: UNRELATED assessment: NPI rationale: KRAS is the GTPase substrate of guanine-nucleotide exchange factors (SOS, RasGRP), not a GEF itself. GTP-bound Ras allosterically stimulates SOS, but that is not exchange-factor activity. A source annotation probably conflated GEF binding/allostery with GEF activity. - claim_id: REJ-05 gene: TNFSF10 organism_dir: human term: GO:0045569 TRAIL binding category: DOWNGRADED assessment: NPI rationale: '''TRAIL binding'' describes receptors (DR4/DR5/decoys) that bind the TRAIL ligand. Here it was transferred, via mouse Tnfsf10, onto the ligand itself. TNFSF10''s only self-interaction is homotrimerization, which identical protein binding captures. The curator''s MODIFY away from this term is correct.' - claim_id: R2-MF-NAR-01 gene: App organism_dir: mouse term: GO:0016504 peptidase activator activity category: NARROWER assessment: NPI rationale: Full-length APP is a secretase substrate, not a peptidase activator; the curator MODIFIED this ISO row to serine-type endopeptidase inhibitor activity, which only the KPI-domain isoforms have. The activator claim probably comes from Abeta-fragment effects (e.g. stimulating tPA in vitro), so the source annotation was itself wrong. - claim_id: R2-MF-UNR-12 gene: PET100 organism_dir: human term: GO:0051082 unfolded protein binding category: UNRELATED assessment: NPI rationale: PET100 is a COX-specific assembly factor that binds COX subunits (e.g. COX7A2) to incorporate them into an early assembly intermediate; there is no evidence it binds unfolded polypeptides. The 'chaperone' label of assembly factors is conflated with folding-chaperone substrate binding (the review marks the related protein folding chaperone/protein folding terms over-annotated). - claim_id: R2-MF-UNR-09 gene: vcla organism_dir: DANRE term: GO:0031625 ubiquitin protein ligase binding category: UNRELATED assessment: NPI rationale: The only source is a human VCL IPI from a Parkin TAP-MS pull-down in which vinculin was one of many abundant cytoskeletal co-purifiers; the human VCL review marks it over-annotated. Nothing links zebrafish vcla, an actin-binding adhesion adaptor, to ubiquitin ligase binding. - claim_id: R2-MF-UNR-03 gene: Idh organism_dir: DROME term: GO:0051990 (R)-2-hydroxyglutarate dehydrogenase activity category: UNRELATED assessment: NPI rationale: Drosophila Idh is a wild-type NADP-isocitrate dehydrogenase. Producing (R)-2-hydroxyglutarate from 2-oxoglutarate is a neomorphic activity of cancer-associated IDH1/IDH2 active-site mutants, and it runs opposite to the dehydrogenase direction the term defines. Neither the wild-type enzyme nor this protein is a 2-HG dehydrogenase. DOMAIN_ARCHITECTURE_MISMATCH: - claim_id: UNR-25 gene: SecA organism_dir: ECOLI term: GO:0015462 ABC-type protein transporter activity category: UNRELATED assessment: NPI rationale: SecA is the cytoplasmic DEAD-motor ATPase that drives preprotein translocation through SecYEG (protein-exporting ATPase activity, EC 7.4.2.8), not an ABC-type transporter (EC 7.4.2.5) with ABC/transmembrane domains; the review accepts GO:0008564 instead. - claim_id: NAR-17 gene: TOMM70 organism_dir: human term: GO:0015450 protein-transporting ATPase activity category: NARROWER assessment: NPI rationale: TOMM70 is a TPR-repeat TOM receptor that docks chaperone-bound precursors; it has no ATPase domain and does not hydrolyse NTPs to drive translocation, so the ATPase-driven primary active transport child of protein transmembrane transporter activity is unsupported. - claim_id: R2-MF-UNR-11 gene: Camk2a organism_dir: mouse term: GO:0005085 guanyl-nucleotide exchange factor activity category: UNRELATED assessment: NPI rationale: CaMKIIalpha is a Ser/Thr kinase made of a catalytic domain, a CaM-binding autoregulatory segment and an association hub; it has no DH, CDC25, SEC7 or DOCK GEF domain. No CaMKII ortholog in the repo carries GEF activity, so the term has no support. - claim_id: R2-MF-REJ-01 gene: groES organism_dir: PSEPK term: GO:0046872 metal ion binding category: REJECTED assessment: NPI rationale: P. putida GroES (97 aa) is a plain Cpn10 beta-barrel with no His/Cys-rich C-terminal extension of the metal-binding HspA-type co-chaperonins and no annotated metal site or cofactor; its function is GroEL capping, so metal ion binding is unsupported and the curator's removal stands. - claim_id: R2-MF-REJ-03 gene: ubl-5 organism_dir: worm term: GO:0031386 protein tag activity category: REJECTED assessment: NPI rationale: UBL-5/Hub1 lacks the C-terminal di-glycine motif needed for covalent conjugation and works through non-covalent binding of HIND-containing spliceosomal proteins and DVE-1. Protein tag activity, which requires covalent attachment to targets, is a ubiquitin-superfamily default that does not apply; the removal stands. - claim_id: R2-MF-REJ-05 gene: cab4 organism_dir: SCHPO term: GO:0004140 dephospho-CoA kinase activity category: REJECTED assessment: NPI rationale: S. pombe cab4 contains only the PPAT-like cytidylyltransferase domain and lacks the dephospho-CoA kinase (CoaE) domain; DPCK activity was transferred from bifunctional COASY-type orthologs. The removal is correct (DPCK in fission yeast is a separate protein). PARALOG_OVERANNOTATION: - claim_id: UNR-13 gene: ccmG organism_dir: PSEPK term: GO:0003756 protein disulfide isomerase activity category: UNRELATED assessment: NPI rationale: CcmG/DsbE is a dedicated periplasmic thiol:disulfide reductase for apocytochrome CXXCH motifs, not a disulfide-shuffling isomerase; PDI activity belongs to other thioredoxin-fold Dsb family members (e.g. DsbC/DsbG). - claim_id: REJ-03 gene: acnA-II organism_dir: PSEPK term: GO:0003994 aconitate hydratase activity category: REJECTED assessment: PLI rationale: AcnA-II (PP_2336) belongs to the AcnD subfamily (IPR012708) and is a dedicated 2-methylcitrate dehydratase in the 2-methylcitrate cycle. Citrate/isocitrate aconitase activity belongs to the canonical AcnA/AcnB paralogs, and the review's removal stands. - claim_id: R2-MF-REJ-02 gene: CRTISO organism_dir: ARATH term: GO:0016491 oxidoreductase activity category: REJECTED assessment: PLI rationale: CRTISO belongs to the carotenoid/retinoid oxidoreductase (CrtI-like) family, but it is a FAD(red)-dependent cis-trans isomerase (EC 5.2.1.13) that carries out a non-redox reaction and has no desaturase activity. The oxidoreductase activity belongs to the desaturase paralogs of the family. - claim_id: R2-MF-NAR-04 gene: fosB organism_dir: STAAT term: GO:0004364 glutathione transferase activity category: NARROWER assessment: PLI rationale: FosB is a divalent-metal-dependent fosfomycin thiol-S-transferase that uses bacillithiol (or L-cysteine) in staphylococci, which lack glutathione; glutathione transferase activity belongs to the FosA subfamily of the fosfomycin-resistance family. The review explicitly states FosB enzymes are not glutathione transferases. COMPLEX_ACTIVITY_TRANSFER: - claim_id: REJ-06 gene: ddb-1 organism_dir: worm term: GO:0003684 damaged DNA binding category: REJECTED assessment: NPI rationale: In UV-DDB, damaged-DNA recognition is provided by DDB2, with DDB1 acting as the CRL4 adaptor; worm DDB-1 is supported only as a CUL-4/DCAF adaptor, so damaged DNA binding is a complex-level activity transferred to the non-binding subunit, consistent with the curator removal of nucleic acid binding. - claim_id: R2-MF-UNR-05 gene: che-3 organism_dir: worm term: GO:0045503 dynein light chain binding category: UNRELATED assessment: NPI rationale: CHE-3 is the dynein-2 heavy chain; its curated direct contacts are the light intermediate chain (XBX-1) and intermediate chains. In dynein complexes the light chains (LC8, Tctex, roadblock) bind the intermediate chains, not the heavy chain, so dynein light chain binding is a complex-level interaction attributed to the heavy chain (only some axonemal heavy chains bind specific LCs directly). - claim_id: R2-MF-UNR-04 gene: Ppp3r1 organism_dir: rat term: GO:0004721 phosphoprotein phosphatase activity category: UNRELATED assessment: NPI rationale: Ppp3r1 (CnB1) is the non-catalytic, EF-hand calcium-binding regulatory subunit of calcineurin; phosphatase catalysis is performed by the PPP3CA/B/C A subunit. The holoenzyme's activity was transferred onto the regulatory subunit. PSEUDOENZYME_OVERANNOTATION: - claim_id: R2-MF-REJ-04 gene: Serpinh1 organism_dir: mouse term: GO:0004867 serine-type endopeptidase inhibitor activity category: REJECTED assessment: NPI rationale: HSP47 keeps the serpin fold but has lost protease-inhibitor activity and works only as an ER collagen-specific chaperone. Inhibitor activity is the ancestral serpin function, transferred by family membership onto a neofunctionalized non-inhibitory serpin. FREQUENCY_BIAS: - claim_id: R2-MF-UNR-08 gene: Rnase1 organism_dir: rat term: GO:0042802 identical protein binding category: UNRELATED assessment: REP rationale: Rat pancreatic RNase is annotated as a monomer (UniProt SUBUNIT). The domain-swapped dimers known for bovine RNase A form under non-physiological in vitro conditions. Identical protein binding is a high-frequency generic term with no specific basis for this protein. PATHWAY_CONTEXT_IGNORED: - claim_id: R2-MF-NAR-06 gene: mut-7 organism_dir: worm term: GO:0044748 3'-5'-exoribonuclease activity involved in mature miRNA 3'-end processing category: NARROWER assessment: NPI rationale: MUT-7 has 3'-5' exoribonuclease activity, but the mature-miRNA 3'-end trimming context comes from Drosophila Nibbler; in C. elegans MUT-7 acts in Mutator-focus 22G siRNA amplification and is required for siRNAs, not miRNAs. The curator marked the same ISS term over-annotated. IN_VITRO_NOT_IN_VIVO: - claim_id: R2-MF-NAR-03 gene: CDC14 organism_dir: yeast term: GO:0004725 protein tyrosine phosphatase activity category: NARROWER assessment: NPI rationale: Cdc14 is a dual-specificity PTP-superfamily enzyme that can hydrolyse phosphotyrosine in vitro, but its physiological substrates are CDK pSer/pThr-Pro sites and pTyr is a poor substrate; the review MODIFYs this EC-mapped term to dual-specificity/Ser-Thr phosphatase. The tyrosine-specific term misrepresents its biological activity.