AGTPBP1 encodes cytosolic carboxypeptidase 1 (CCP1), a zinc-dependent protein deglutamylase. It hydrolyzes terminal alpha-linked glutamates from polyglutamylated tubulin side chains and from gene-encoded tubulin C termini, generating delta2- and delta3-tubulin. On the tubulin substrates examined, CCP1 shortens glutamate chains without removing the gamma-linked branching glutamate. This activity controls microtubule modification and supports neuronal integrity. CCP1 is predominantly studied in the cytoplasmic microtubule system; nuclear distribution and a mitochondrial-associated pool have also been reported. Reported non-tubulin substrates include myosin light-chain kinase; KLF4 deglutamylation is described in reprogramming studies. Biallelic loss-of-function variants cause childhood-onset neurodegeneration with cerebellar atrophy, affecting the central and peripheral nervous systems.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0001754 eye photoreceptor cell differentiation | ISS GO_REF:0000024 | UNDECIDED | Summary: Mouse photoreceptor donor evidence is resolved to a degeneration study; differentiation remains uncertain. Reason: Q641K1 is mouse Agtpbp1. The historical MGI graph links this differentiation assertion to J:105316 (PMID:16465590). Its primary abstract establishes the pcd5J allele, loss of protein stability and photoreceptor degeneration, but the full paper was not recovered. The human disease study also reports a retinal phenotype difference between species. Conserved deglutamylase activity makes a neuronal role plausible, but neither absence of a human assay nor the visible degeneration phenotype settles this particular differentiation claim. Retain uncertainty pending the developmental evidence and its transfer context. Propagation Review Root cause: UNRESOLVED Sources checked: UniProtKB:Q641K1 UNRESOLVED Mouse identity and MGI J:105316βPMID:16465590 are verified. The primary abstract is accessible; differentiation-specific full results and their human conservation remain unresolved. |
| GO:0004181 metallocarboxypeptidase activity | IBA GO_REF:0000033 | ACCEPT | Summary: Inherited metallocarboxypeptidase activity agrees with direct human CCP1 assays. Reason: The PAINT assertion is consistent with the human enzyme preparations and tubulin processing demonstrated in PMID:22170066 and PMID:24022482. Human CCP1 is among the descendant evidences; self-evidence is legitimate experimental grounding, not circular propagation. The exact ancestral placement was not independently reconstructed. This MF describes the measured metal-dependent exopeptidase chemistry without incorrectly assigning terminal tyrosine removal. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN007589887 UNRESOLVED The exact IBD node was not independently recovered. Retain the curated inherited function because direct human CCP1 enzymology supports the target; the human descendant is valid evidence. Supporting Evidence: PMID:22170066 Purified CCP1 produced delta2-tubulin from purified porcine brain Ξ±-tubulin or polymerized HEK293T microtubules. |
| GO:0004181 metallocarboxypeptidase activity | IDA PMID:22170066 Cytosolic carboxypeptidase 1 is involved in processing Ξ±- an... | ACCEPT | Summary: Human CCP1 directly processes tubulin C-terminal glutamates. Reason: The original full PMC3307270 Methods identify recombinant human CCP1 expressed in Sf9 cells. Affinity-enriched CCP1, with wild-type-baculovirus purification controls, processes purified tubulin and polymerized microtubules; phenanthroline inhibits the reaction. Mass spectrometry resolves glutamate removal. The metal-dependent carboxypeptidase term is appropriate and is not a claim that CCP1 is a general intracellular peptide-degradation enzyme. Supporting Evidence: PMID:22170066 Purified CCP1 produced delta2-tubulin from purified porcine brain Ξ±-tubulin or polymerized HEK293T microtubules. |
| GO:0004181 metallocarboxypeptidase activity | IEA GO_REF:0000120 | ACCEPT | Summary: The electronic metallopeptidase assignment is experimentally supported in human CCP1. Reason: InterPro peptidase-domain mappings agree with direct human CCP1 catalysis. The ARBA rule internals were not recovered, so the rule is not independently certified; the target annotation is retained on measured activity in PMID:22170066, without inferring substrate specificity from the family name. Propagation Review Root cause: NO FAILURE CORE Sources checked: ARBA:ARBA00028163 UNRESOLVED Rule internals were not independently read; annotation judgment rests on direct target enzymology. InterPro:IPR000834 SUPPORTS TRANSFER The M14 carboxypeptidase domain is present in the immutable UniProt record and agrees with measured metal-dependent activity. InterPro:IPR033852 SUPPORTS TRANSFER CCP1 family assignment agrees with the verified human protein identity and activity; no new residue-level inference is required. Supporting Evidence: PMID:22170066 Purified CCP1 produced delta2-tubulin from purified porcine brain Ξ±-tubulin or polymerized HEK293T microtubules. |
| GO:0004181 metallocarboxypeptidase activity | ISS GO_REF:0000024 | ACCEPT | Summary: Mouse-to-human transfer of metallocarboxypeptidase activity is directly corroborated. Reason: The mouse donor is the orthologous CCP1, with the historical MGI chain including PMID:21074048. Independent recombinant human assays in PMID:22170066 and PMID:24022482 establish the same terminal-glutamate hydrolysis. This is not a transfer based only on a conserved fold. Propagation Review Root cause: NO FAILURE CORE Sources checked: UniProtKB:Q641K1 SUPPORTS TRANSFER Q641K1 is mouse Agtpbp1; MGI J:166837 identifies the 2010 deglutamylase study. Human assays independently establish the transferred activity. Supporting Evidence: PMID:22170066 Purified CCP1 produced delta2-tubulin from purified porcine brain Ξ±-tubulin or polymerized HEK293T microtubules. |
| GO:0005634 nucleus | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: Nuclear localization is supported but is not a separate core activity. Reason: The PAINT nuclear assertion is compatible with the human UniProt localization curated from PMID:23085998 and independent HPA nucleoplasmic staining. The precise ancestral-node placement was not recovered; neither the short source list nor inclusion of the human protein is a defect. Nuclear residence is retained as contextual localization, without inventing a distinct nuclear enzymatic mechanism. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: PANTHER:PTN002654088 UNRESOLVED Exact IBD placement remains unverified. Human curated nuclear localization and independently read HPA staining support the target assertion; self-evidence is not circular. Supporting Evidence: file:human/AGTPBP1/AGTPBP1-uniprot.txt the cytoplasm and nuclei of interphase and dividing cells. |
| GO:0005634 nucleus | IDA PMID:23085998 Functional segregation and emerging role of cilia-related cy... | KEEP AS NON CORE | Summary: Retain the curated nuclear localization with an explicit source-access limit. Reason: The cached abstract of PMID:23085998 describes the CCP family and HeLa localization experiments but does not expose the CCP1-specific nuclear panel. The human UniProt record explicitly attributes interphase/dividing-cell nuclear distribution to this source, and HPA independently supports nucleoplasm. Defer to that positive curation rather than rejecting the annotation from the family-focused abstract. Retain a contextual nuclear pool; the unavailable full source prevents a more detailed construct or cell-cycle claim. Supporting Evidence: file:human/AGTPBP1/AGTPBP1-uniprot.txt the cytoplasm and nuclei of interphase and dividing cells. |
| GO:0005634 nucleus | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: The UniProt nuclear-location mapping is appropriate. Reason: SL-0191 maps the curated human nuclear location. It agrees with HPA nucleoplasm evidence and the PMID:23085998 provenance in UniProt. Nuclear localization is retained without treating the mapped record as an independent experiment or asserting a dedicated nuclear core function. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: UniProtKB-SubCell:SL-0191 SUPPORTS TRANSFER The source vocabulary term maps the explicit nuclear localization in Q9UPW5; its evidence provenance remains PMID:23085998. Supporting Evidence: file:human/AGTPBP1/AGTPBP1-uniprot.txt the cytoplasm and nuclei of interphase and dividing cells. |
| GO:0005654 nucleoplasm | IDA GO_REF:0000052 | KEEP AS NON CORE | Summary: HPA supports a nucleoplasmic pool. Reason: The primary HPA AGTPBP1 subcellular page, read on 2026-09-27, rates nucleoplasm as supported and lists HPA071094 staining in SH-SY5Y, SK-MEL-30 and U2OS. This supports the seeded compartment. It does not establish that all CCP1 molecules reside there or identify a separate nuclear catalytic pathway. Additional HPA locations have different reliability grades and are not transferred into this assertion. The supporting notes preserve the directly read HPA statement and URL as a primary-source receipt; the UniProt GO cross-reference is not independent evidence. Supporting Evidence: file:human/AGTPBP1/AGTPBP1-notes.md Localized to the Nucleoplasm (supported) |
| GO:0005737 cytoplasm | EXP PMID:17244818 A novel subfamily of mouse cytosolic carboxypeptidases. | ACCEPT | Summary: Retain the broad cytoplasmic compartment supported by the source and independent human work. Reason: The original abstract explicitly reports cytosolic Nna1/CCP1 distribution in its mouse-family study. Full experimental construct provenance was not recovered, so the title is not used to overrule the curated human EXP row. The cytoplasmic compartment is independently consistent with human CCP1 processing of cellular tubulin in PMID:22170066 and the localization record. Preserve the source-level broad compartment. Supporting Evidence: PMID:17244818 Nna1/CCP1, CCP2, CCP5, and CCP6 were found to exhibit a cytosolic distribution file:human/AGTPBP1/AGTPBP1-uniprot.txt -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:17244818, CC ECO:0000269|PubMed:23085998}. |
| GO:0005737 cytoplasm | IBA GO_REF:0000033 | ACCEPT | Summary: The inherited cytoplasmic compartment fits CCP1 tubulin processing. Reason: Direct human cellular and biochemical assays support the cytoplasmic microtubule context. The PAINT node was not independently reconstructed; its exact placement is deferred to the curator rather than replaced by a donor-count argument. This broad location remains valid alongside more precise cytosol assertions. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN007589887 UNRESOLVED Node internals were not recovered. Target enzymology and curated localization support the cytoplasmic assertion; no lineage-specific localization loss was established. Supporting Evidence: PMID:17244818 Nna1/CCP1, CCP2, CCP5, and CCP6 were found to exhibit a cytosolic distribution file:human/AGTPBP1/AGTPBP1-uniprot.txt -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:17244818, CC ECO:0000269|PubMed:23085998}. |
| GO:0005737 cytoplasm | IDA PMID:23085998 Functional segregation and emerging role of cilia-related cy... | ACCEPT | Summary: Retain the curated cytoplasmic localization. Reason: Q9UPW5 explicitly records cytoplasm from PMID:23085998. The cached family-level abstract does not resolve every CCP1 panel, but the localization agrees with human tubulin-processing assays and the other source-level cytoplasmic evidence. Accept at the source resolution without assigning every family ciliary location to CCP1. Supporting Evidence: PMID:17244818 Nna1/CCP1, CCP2, CCP5, and CCP6 were found to exhibit a cytosolic distribution file:human/AGTPBP1/AGTPBP1-uniprot.txt -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:17244818, CC ECO:0000269|PubMed:23085998}. |
| GO:0005737 cytoplasm | IEA GO_REF:0000044 | ACCEPT | Summary: The cytoplasm vocabulary mapping describes the core cellular compartment. Reason: SL-0086 is an appropriate mapping of the explicit UniProt cytoplasmic record. Human CCP1 processing of cellular tubulin supports the biological context. A broad supported compartment does not need replacement merely because a cytosol annotation also exists. Propagation Review Root cause: NO FAILURE CORE Sources checked: UniProtKB-SubCell:SL-0086 SUPPORTS TRANSFER The source vocabulary mapping faithfully represents the Q9UPW5 cytoplasm statement. Supporting Evidence: PMID:17244818 Nna1/CCP1, CCP2, CCP5, and CCP6 were found to exhibit a cytosolic distribution file:human/AGTPBP1/AGTPBP1-uniprot.txt -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:17244818, CC ECO:0000269|PubMed:23085998}. |
| GO:0005739 mitochondrion | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: Retain the inferred mitochondrial-associated pool with its rodent provenance. Reason: The UniProt mitochondrial statement is explicitly by similarity to mouse Q641K1. PMID:20620870 provides positive rodent fractionation with compartment controls: rat brain mitochondrial enrichment and mouse liver subfractionation. These data support a contextual pool, while its abundance and submitochondrial topology in human cells are not directly established here. A cytosolic core does not imply that the fractionated pool is contamination. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: UniProtKB-SubCell:SL-0173 SUPPORTS TRANSFER The vocabulary mapping preserves a curated similarity-based mitochondrial location; the underlying mouse/rat source evidence is explicitly bounded, not represented as a human localization assay. Supporting Evidence: file:human/AGTPBP1/AGTPBP1-uniprot.txt Mitochondrion {ECO:0000250|UniProtKB:Q641K1}. PMID:20620870 Mouse liver sub-mitochondrial fractions were generated as previously described (Wiley et al., 2009), with minor modification. PMID:20620870 we performed a sub-mitochondrial fractionation experiment and determined that Nna1 is enriched in the outer membrane of the mitochondria (Figure 5B). |
| GO:0005739 mitochondrion | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Mouse CCP1 mitochondrial localization is a defensible contextual transfer. Reason: The historical MGI graph traces mitochondrial IDA for mouse Agtpbp1 to J:163166, PMID:20620870. Its full Figure 5 distinguishes rat brain/spinal-cord fractions from mouse liver submitochondrial fractions and includes localization markers. The mouse liver result supplies positive evidence for the actual donor. Retain the curator-supported ortholog transfer at whole-organelle resolution; do not assign human matrix or outer-membrane topology from these data. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: UniProtKB:Q641K1 SUPPORTS TRANSFER Verified mouse Q641K1 donor and MGI J:163166βPMID:20620870. Full Figure 5B provides mouse liver fractionation; Figure 5A is rat tissue. Transfer remains broad and similarity-based. Supporting Evidence: file:human/AGTPBP1/AGTPBP1-uniprot.txt Mitochondrion {ECO:0000250|UniProtKB:Q641K1}. PMID:20620870 Mouse liver sub-mitochondrial fractions were generated as previously described (Wiley et al., 2009), with minor modification. PMID:20620870 we performed a sub-mitochondrial fractionation experiment and determined that Nna1 is enriched in the outer membrane of the mitochondria (Figure 5B). |
| GO:0005829 cytosol | IEA GO_REF:0000044 | ACCEPT | Summary: Cytosol is a core compartment for CCP1. Reason: The UniProt cytosol mapping is consistent with the original CCP1 cytosolic distribution and human protein-deglutamylation assays. This cellular location is appropriate even though additional nuclear and mitochondrial-associated pools have been reported. Propagation Review Root cause: NO FAILURE CORE Sources checked: UniProtKB-SubCell:SL-0091 SUPPORTS TRANSFER Q9UPW5 explicitly records cytosol by similarity to Q641K1; the original mouse distribution study is consistent with this mapping. Supporting Evidence: file:human/AGTPBP1/AGTPBP1-uniprot.txt Cytoplasm, cytosol CC {ECO:0000250|UniProtKB:Q641K1}. PMID:17244818 Nna1/CCP1, CCP2, CCP5, and CCP6 were found to exhibit a cytosolic distribution |
| GO:0005829 cytosol | ISS GO_REF:0000024 | ACCEPT | Summary: The mouse cytosol annotation transfers plausibly to human CCP1. Reason: Mouse Agtpbp1 is the orthologous cytosolic deglutamylase. The MGI source chain and PMID:17244818 support cytosolic distribution; human tubulin processing and the curated Q9UPW5 compartment corroborate conservation. No source-specific compartment divergence was found. Propagation Review Root cause: NO FAILURE CORE Sources checked: UniProtKB:Q641K1 SUPPORTS TRANSFER Mouse identity is verified; the historical cytosolic localization chain includes J:168198/PMID:17244818. Independent human functional context supports conservation without converting ISS into IDA. Supporting Evidence: PMID:17244818 Nna1/CCP1, CCP2, CCP5, and CCP6 were found to exhibit a cytosolic distribution file:human/AGTPBP1/AGTPBP1-uniprot.txt -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:17244818, CC ECO:0000269|PubMed:23085998}. |
| GO:0006508 proteolysis | IEA GO_REF:0000002 | MODIFY | Summary: Refine broad proteolysis to the two directly measured glutamate-removal processes. Reason: The M14 domain correctly indicates hydrolytic peptide-bond cleavage, but the human assays identify protein modification rather than indiscriminate protein turnover. CCP1 removes gene-encoded terminal glutamates and shortens polyglutamylated side chains. GO:0035609 and GO:0035610 distinguish those two measured processes. They are sibling protein-modification terms, not claimed to be formal children of proteolysis; no redundant NEW annotation is added. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH Sources checked: InterPro:IPR000834 SUPPORTS TRANSFER The peptidase-domain mapping captures genuine hydrolysis but not the demonstrated substrate-specific modification processes. Proposed replacements: C-terminal protein deglutamylation protein side chain deglutamylation Supporting Evidence: PMID:22170066 Purified CCP1 produced delta2-tubulin from purified porcine brain Ξ±-tubulin or polymerized HEK293T microtubules. PMID:22170066 CCP1 removed Glu residues from the polyglutamyl side chains |
| GO:0007005 mitochondrion organization | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Retain CCP1-dependent mitochondrial organization as a contextual process. Reason: The mouse donor chain maps to PMID:20620870, which reports mitochondrial abnormalities and positive localization. Independent full PMID:30337352 tests human RPE1 CCP1-null cells, quantifies reduced mitochondrial fusion, and compares enzymatically active and inactive CCP1 under mitochondrial stress. Mouse neuronal transport measurements support a microtubule-modification mechanism, although the link between transport and fusion remains a model. This supports the broad organization process without making CCP1 a fusion GTPase or asserting a direct mitochondrial substrate. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: UniProtKB:Q641K1 SUPPORTS TRANSFER Historical mouse mitochondrial-organization IMP points to J:163166/PMID:20620870. Human RPE1 loss-of-function and catalytic-dependence experiments in PMID:30337352 independently support target participation. Supporting Evidence: PMID:30337352 when we counted individual mitochondrial fusion events, we detected a significant reduction in the rate of mitochondrial fusion in CCP1 null RPE cells (Fig. 4 C). |
| GO:0008270 zinc ion binding | IEA GO_REF:0000002 | ACCEPT | Summary: Zinc binding is consistent with the catalytic metallopeptidase domain. Reason: The InterPro M14 domain and curated UniProt zinc-cofactor assignment agree with metal-chelator inhibition of recombinant human CCP1. The UniProt one-zinc stoichiometry is inferred by similarity, not a direct human metal-occupancy measurement in the papers examined. Retain this cofactor-binding annotation without promoting the inferred stoichiometry to a new experiment. UniProt assigns catalytic zinc-binding features at residues 920, 923 and 1017 through PROSITE-ProRule evidence; these inferred residue assignments are not direct occupancy measurements. Propagation Review Root cause: NO FAILURE CORE Sources checked: InterPro:IPR000834 SUPPORTS TRANSFER M14 catalytic-domain assignment and curated zinc cofactor support binding; no residue-loss argument or invented human stoichiometry is used. Supporting Evidence: file:human/AGTPBP1/AGTPBP1-uniprot.txt FT BINDING 920 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_note="catalytic" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01379" |
| GO:0015630 microtubule cytoskeleton | IBA GO_REF:0000033 | ACCEPT | Summary: The microtubule cytoskeleton is the site of the established tubulin-processing activity. Reason: Human CCP1 acts on polymerized HEK293T microtubules in PMID:22170066. This supports the cytoskeletal context of the inherited annotation. The PAINT assertion is retained without claiming that all family members share identical ciliary localization or that CCP1 is a stoichiometric microtubule structural subunit. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN007589887 UNRESOLVED Exact node placement remains unverified; direct target activity on polymerized microtubules supports the asserted context independently of donor count. Supporting Evidence: PMID:22170066 Purified CCP1 produced delta2-tubulin from purified porcine brain Ξ±-tubulin or polymerized HEK293T microtubules. |
| GO:0015631 tubulin binding | IBA GO_REF:0000033 | ACCEPT | Summary: Tubulin recognition is integral to the inherited substrate-processing function. Reason: Tubulin is a demonstrated substrate of human CCP1. Retain the substrate-specific binding term as part of that interaction, not as a separate scaffolding activity or a measured affinity claim. The family-level PAINT assertion is consistent with human biochemical activity, while its exact ancestral reconstruction remains unexamined. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN007589887 UNRESOLVED The IBD reconstruction was not retrieved; substrate recognition in direct human assays supports the target binding assertion without inventing an affinity measurement. Supporting Evidence: PMID:22170066 Purified CCP1 produced delta2-tubulin from purified porcine brain Ξ±-tubulin or polymerized HEK293T microtubules. |
| GO:0015631 tubulin binding | ISS GO_REF:0000024 | ACCEPT | Summary: Mouse tubulin-binding transfer agrees with direct human substrate processing. Reason: The historical MGI mouse tubulin-binding IDA points to J:166837, PMID:21074048. Independent human CCP1 assays use purified tubulin and polymerized microtubules, supporting the relevant substrate recognition. This term does not establish a noncatalytic tubulin scaffold role. Propagation Review Root cause: NO FAILURE CORE Sources checked: UniProtKB:Q641K1 SUPPORTS TRANSFER Mouse Agtpbp1 and the J:166837/PMID:21074048 binding chain are verified; direct human tubulin processing corroborates transfer. Supporting Evidence: PMID:22170066 Purified CCP1 produced delta2-tubulin from purified porcine brain Ξ±-tubulin or polymerized HEK293T microtubules. |
| GO:0021702 cerebellar Purkinje cell differentiation | ISS GO_REF:0000024 | UNDECIDED | Summary: Purkinje-cell integrity is established; the differentiation-specific transfer remains unresolved. Reason: The mouse MGI graph includes PMID:11884758, PMID:16465590, PMID:21074048 and PMID:30337352 in its differentiation evidence chain. The original PMID:11884758 main article is now externally accessible and establishes mouse allele identity, postweaning degeneration and adult expression. The full PMID:16465590 and PMID:21074048 bodies remain unread; the former abstract concerns protein destabilization and degeneration. Later full experiments establish deglutamylation, neuronal survival and mitochondrial dynamics, but do not by themselves resolve the earlier differentiation assertion. Human disease involves cerebellar atrophy, while PMID:30420557 explicitly lacks direct human Purkinje histology. Preserve the ISS assertion pending its exact developmental evidence rather than treating degeneration as proof of either differentiation or its absence. Propagation Review Root cause: UNRESOLVED Sources checked: UniProtKB:Q641K1 UNRESOLVED The mouse source and multiple historical MGI references are recovered. PMID:11884758 main text is read, but the full PMID:16465590 and PMID:21074048 studies and the 2002 supplement remain unavailable. The exact differentiation assay remains unresolved; positive maintenance evidence is retained separately. |
| GO:0021772 olfactory bulb development | ISS GO_REF:0000024 | UNDECIDED | Summary: The recovered mouse main article establishes adult neuronal maintenance; developmental transfer remains unresolved. Reason: The historical mouse donor graph points to J:74929, PMID:11884758. Its original main article (Science 295:1904β1906, author-uploaded copy read 2026-09-27) reports postweaning neuronal degeneration and one-month-old mouse in-situ expression in olfactory mitral cells (Figure 5); it does not itself resolve formation-to-maturity of the olfactory bulb as defined by GO:0021772. The linked supplement and erratum body were not recovered. Retain UNDECIDED for the precise developmental source claim and its conservation, while accepting the positive maintenance phenotype; neither lack of a direct human assay nor degeneration alone disproves a developmental role. Propagation Review Root cause: UNRESOLVED Sources checked: UniProtKB:Q641K1 UNRESOLVED Mouse Q641K1 and MGI J:74929βPMID:11884758 are verified. The original main text now resolves adult expression and degeneration; developmental assay details in the inaccessible supplement and the scope of the linked erratum remain unresolved. |
| GO:0050905 neuromuscular process | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: A broad neuromuscular role is consistent with conserved neuronal deglutamylation and human disease. Reason: GO:0050905 covers processes pertaining to nervous and muscular system function; it is not limited to neuromuscular-junction formation. The mouse MGI source includes PMID:11884758. Independent PMID:30420557 establishes human central/peripheral neurodegeneration, endogenous CCP1 loss and excess tubulin glutamylation in muscle, with mouse motor-neuron and peripheral-nerve pathology. Together with direct human CCP1 enzymology, these support the broad physiological role. Retain it as a non-core organismal context without assigning neurotransmission or a specific developmental mechanism. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: UniProtKB:Q641K1 SUPPORTS TRANSFER The historical mouse donor chain includes J:74929/PMID:11884758; its original main text now confirms the adult neuronal phenotype. Independent human/mouse evidence in PMID:30420557 supports the broad conserved neuromuscular role, not a specific synaptic activity. Supporting Evidence: PMID:30420557 The human disease mainly affected the cerebellum, spinal motor neurons, and peripheral nerves. PMID:30420557 We also demonstrate previously unrecognized peripheral nerve and spinal motor neuron degeneration in pcd mice |
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Download this section (compressed HTML)Q: Which full experiments underlying the mouse photoreceptor/Purkinje differentiation and olfactory-bulb development annotations distinguish developmental participation from maintenance of mature neurons, and how do those findings transfer to human AGTPBP1?
Q: What fraction of endogenous human CCP1 resides in mitochondria or nuclei, and which substrates are directly processed in each compartment? Existing rodent fractionation and nuclear staining do not by themselves identify compartment-specific catalysis.
Q: Which human CCP1 isoforms account for the documented localization and substrate activities? The three sequence products are preserved, but most experiments do not resolve them.
Q: Does the effect on mitochondrial fusion arise entirely through tubulin-dependent motility, or are additional CCP1 substrates involved? Catalytic-dependence and transport results support participation but do not settle this causal route.
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