id: Q96CF2 gene_symbol: CHMP4C product_type: PROTEIN status: COMPLETE taxon: id: NCBITaxon:9606 label: Homo sapiens description: CHMP4C encodes a Snf7-family ESCRT-III paralog with a specialized role in Aurora B/NoCut abscission checkpoint control. Unlike CHMP4B, which is the main CHMP4 paralog required for MHC-I degradation, HIV release, and cytokinesis execution in key paralog-comparison assays, CHMP4C delays abscission when chromosome segregation or checkpoint signals persist. Aurora B-phosphorylated CHMP4C localizes to the midbody/Flemming body, works with Borealin/CPC and ANCHR/ZFYVE19, and retains VPS4 at the midbody ring until checkpoint signaling is terminated. Broader ESCRT/MVB/autophagy annotations are plausible family context but should not obscure this core checkpoint-regulatory function. existing_annotations: - term: id: GO:0005635 label: nuclear envelope evidence_type: IBA original_reference_id: GO_REF:0000033 qualifier: is_active_in review: summary: 'Plausible non-core CHMP4C nuclear-envelope ESCRT context: nuclear envelope.' action: KEEP_AS_NON_CORE reason: Nuclear envelope sealing/reassembly is a supported ESCRT-III context, but it is secondary to the CHMP4C-specific abscission-checkpoint role. supported_by: - reference_id: PMID:26040712 supporting_text: ESCRT-III, VPS4 and spastin cooperate to coordinate nuclear envelope sealing and spindle disassembly - reference_id: PMID:26040713 supporting_text: ESCRT-III controls nuclear envelope reformation - term: id: GO:0031468 label: nuclear membrane reassembly evidence_type: IBA original_reference_id: GO_REF:0000033 qualifier: involved_in review: summary: 'Plausible non-core CHMP4C nuclear-envelope ESCRT context: nuclear membrane reassembly.' action: KEEP_AS_NON_CORE reason: Nuclear envelope sealing/reassembly is a supported ESCRT-III context, but it is secondary to the CHMP4C-specific abscission-checkpoint role. supported_by: - reference_id: PMID:26040712 supporting_text: ESCRT-III, VPS4 and spastin cooperate to coordinate nuclear envelope sealing and spindle disassembly - reference_id: PMID:26040713 supporting_text: ESCRT-III controls nuclear envelope reformation - term: id: GO:0000815 label: ESCRT III complex evidence_type: IBA original_reference_id: GO_REF:0000033 qualifier: part_of review: summary: 'Supported CHMP4C ESCRT-III complex membership annotation: ESCRT III complex.' action: ACCEPT reason: CHMP4C is a Snf7-family CHMP4 subunit of ESCRT-III; its most specific cellular function is checkpoint regulation, but complex membership is sound. supported_by: - reference_id: UniProt:Q96CF2 supporting_text: Probable core component of the endosomal sorting required for transport complex III (ESCRT-III) - reference_id: UniProt:Q96CF2 supporting_text: ESCRT-III proteins mostly dissociate from the invaginating membrane before the ILV is released - reference_id: PMID:18511562 supporting_text: Bro1 domain of ALIX binds specifically to C-terminal residues of the human CHMP4 proteins (CHMP4A-C) - reference_id: PMID:36107470 supporting_text: CHMP4C performs a unique role in abscission checkpoint regulation - reference_id: file:human/CHMP4C/CHMP4C-notes.md supporting_text: CHMP4C still has bona fide ESCRT-III context. - term: id: GO:0009898 label: cytoplasmic side of plasma membrane evidence_type: IBA original_reference_id: GO_REF:0000033 qualifier: is_active_in review: summary: 'True or plausible broad CHMP4C location: cytoplasmic side of plasma membrane.' action: KEEP_AS_NON_CORE reason: This location is compatible with CHMP4C cycling between cytosol and recruited ESCRT-III assemblies, but it is too broad to represent the core function by itself. supported_by: - reference_id: UniProt:Q96CF2 supporting_text: Cytoplasm. Cytosol - reference_id: UniProt:Q96CF2 supporting_text: Localizes to the midbody during late cytokinesis - term: id: GO:0032511 label: late endosome to vacuole transport via multivesicular body sorting pathway evidence_type: IBA original_reference_id: GO_REF:0000033 qualifier: involved_in review: summary: 'Plausible but non-core CHMP4C ESCRT/MVB context: late endosome to vacuole transport via multivesicular body sorting pathway.' action: KEEP_AS_NON_CORE reason: CHMP4C belongs to the CHMP4/ESCRT-III family, but CHMP4C-specific evidence points most strongly to abscission-checkpoint regulation; MVB/endosomal sorting annotations are retained as non-core ESCRT-family context. supported_by: - reference_id: UniProt:Q96CF2 supporting_text: involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs - reference_id: PMID:18511562 supporting_text: The ESCRT pathway facilitates membrane fission events during enveloped virus budding, multivesicular body formation, and cytokinesis - reference_id: PMID:22422861 supporting_text: depletion of CHMP4B prevented MHC-I degradation, whereas depletion of CHMP4A or CHMP4C had little effect - reference_id: file:human/CHMP4C/CHMP4C-notes.md supporting_text: broad MVB cargo-degradation annotations for CHMP4C should be retained, at most, as non-core/over-annotated ESCRT-family context - term: id: GO:0000776 label: kinetochore evidence_type: IEA original_reference_id: GO_REF:0000117 qualifier: located_in review: summary: 'Plausible non-core CHMP4C centrosome/spindle/cell-cycle context: kinetochore.' action: KEEP_AS_NON_CORE reason: ESCRT-III/VPS4 perturbation affects centrosome and spindle maintenance, but these broad cell-cycle annotations are secondary to CHMP4C abscission-checkpoint regulation. supported_by: - reference_id: PMID:20616062 supporting_text: depletion of individual ESCRT-III and VPS4 proteins also altered centrosome and spindle pole numbers - reference_id: PMID:20616062 supporting_text: ESCRT-III/VPS4 proteins function at centrosomes to help regulate their maintenance or proliferation and then at midbodies during abscission - term: id: GO:0001778 label: plasma membrane repair evidence_type: IEA original_reference_id: GO_REF:0000117 qualifier: involved_in review: summary: Plausible non-core CHMP4C plasma-membrane repair ESCRT context. action: KEEP_AS_NON_CORE reason: Plasma membrane repair is a valid ESCRT output context, but the available CHMP4C-specific evidence points to abscission-checkpoint regulation rather than plasma repair as core function. supported_by: - reference_id: PMID:24482116 supporting_text: ESCRT proteins were recruited within seconds to plasma membrane wounds - reference_id: PMID:24482116 supporting_text: repair of certain wounds is ensured by ESCRT-mediated extracellular shedding of wounded portions - term: id: GO:0005643 label: nuclear pore evidence_type: IEA original_reference_id: GO_REF:0000117 qualifier: part_of review: summary: 'Plausible non-core CHMP4C nuclear-envelope ESCRT context: nuclear pore.' action: KEEP_AS_NON_CORE reason: Nuclear envelope sealing/reassembly is a supported ESCRT-III context, but it is secondary to the CHMP4C-specific abscission-checkpoint role. supported_by: - reference_id: PMID:26040712 supporting_text: ESCRT-III, VPS4 and spastin cooperate to coordinate nuclear envelope sealing and spindle disassembly - reference_id: PMID:26040713 supporting_text: ESCRT-III controls nuclear envelope reformation - term: id: GO:0005765 label: lysosomal membrane evidence_type: IEA original_reference_id: GO_REF:0000117 qualifier: located_in review: summary: 'Plausible PN-relevant but non-core CHMP4C autophagy/endolysosomal context: lysosomal membrane.' action: KEEP_AS_NON_CORE reason: The PN places CHMP4C in an ESCRT-III autophagophore closure bucket and ESCRT/MVB function supports autophagic clearance, but cached CHMP4C-specific papers do not directly test CHMP4C as the phagophore sealing effector. supported_by: - reference_id: PMID:17984323 supporting_text: Functional multivesicular bodies are required for autophagic clearance - reference_id: PMID:17984323 supporting_text: autophagic degradation is inhibited in cells depleted of ESCRT subunits - reference_id: file:human/CHMP4C/CHMP4C-notes.md supporting_text: the cached CHMP4C-specific papers do not directly assay CHMP4C as the phagophore sealing effector - term: id: GO:0005828 label: kinetochore microtubule evidence_type: IEA original_reference_id: GO_REF:0000117 qualifier: located_in review: summary: 'Plausible non-core CHMP4C centrosome/spindle/cell-cycle context: kinetochore microtubule.' action: KEEP_AS_NON_CORE reason: ESCRT-III/VPS4 perturbation affects centrosome and spindle maintenance, but these broad cell-cycle annotations are secondary to CHMP4C abscission-checkpoint regulation. supported_by: - reference_id: PMID:20616062 supporting_text: depletion of individual ESCRT-III and VPS4 proteins also altered centrosome and spindle pole numbers - reference_id: PMID:20616062 supporting_text: ESCRT-III/VPS4 proteins function at centrosomes to help regulate their maintenance or proliferation and then at midbodies during abscission - term: id: GO:0005829 label: cytosol evidence_type: IEA original_reference_id: GO_REF:0000044 qualifier: located_in review: summary: 'True or plausible broad CHMP4C location: cytosol.' action: KEEP_AS_NON_CORE reason: This location is compatible with CHMP4C cycling between cytosol and recruited ESCRT-III assemblies, but it is too broad to represent the core function by itself. supported_by: - reference_id: UniProt:Q96CF2 supporting_text: Cytoplasm. Cytosol - reference_id: UniProt:Q96CF2 supporting_text: Localizes to the midbody during late cytokinesis - term: id: GO:0007034 label: vacuolar transport evidence_type: IEA original_reference_id: GO_REF:0000002 qualifier: involved_in review: summary: 'CHMP4C annotation should be replaced with a less over-specific ESCRT/MVB term: vacuolar transport.' action: MODIFY reason: Vacuolar transport is too broad; if retained for CHMP4C it should be framed as general MVB sorting context, not core CHMP4C checkpoint function. supported_by: - reference_id: UniProt:Q96CF2 supporting_text: involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs - reference_id: PMID:18511562 supporting_text: The ESCRT pathway facilitates membrane fission events during enveloped virus budding, multivesicular body formation, and cytokinesis - reference_id: PMID:22422861 supporting_text: depletion of CHMP4B prevented MHC-I degradation, whereas depletion of CHMP4A or CHMP4C had little effect - reference_id: file:human/CHMP4C/CHMP4C-notes.md supporting_text: broad MVB cargo-degradation annotations for CHMP4C should be retained, at most, as non-core/over-annotated ESCRT-family context proposed_replacement_terms: - id: GO:0071985 label: multivesicular body sorting pathway - term: id: GO:0007080 label: mitotic metaphase chromosome alignment evidence_type: IEA original_reference_id: GO_REF:0000117 qualifier: involved_in review: summary: 'Plausible non-core CHMP4C centrosome/spindle/cell-cycle context: mitotic metaphase chromosome alignment.' action: KEEP_AS_NON_CORE reason: ESCRT-III/VPS4 perturbation affects centrosome and spindle maintenance, but these broad cell-cycle annotations are secondary to CHMP4C abscission-checkpoint regulation. supported_by: - reference_id: PMID:20616062 supporting_text: depletion of individual ESCRT-III and VPS4 proteins also altered centrosome and spindle pole numbers - reference_id: PMID:20616062 supporting_text: ESCRT-III/VPS4 proteins function at centrosomes to help regulate their maintenance or proliferation and then at midbodies during abscission - term: id: GO:0030496 label: midbody evidence_type: IEA original_reference_id: GO_REF:0000117 qualifier: located_in review: summary: 'Supported core CHMP4C cytokinesis-checkpoint location: midbody.' action: ACCEPT reason: CHMP4C localizes to the midbody and Flemming body during late cytokinesis, with timing and localization tied to its Aurora B-dependent abscission-checkpoint function. supported_by: - reference_id: PMID:22422861 supporting_text: GFP-CHMP4C localized earlier to the midbody - reference_id: PMID:22422861 supporting_text: HA-CHMP4C localised to the Flemming-body in an INS-dependent manner - reference_id: PMID:22422861 supporting_text: Aurora B-dependent phosphorylation of S210 allows CHMP4C localization to the Flemming body - term: id: GO:0031468 label: nuclear membrane reassembly evidence_type: IEA original_reference_id: GO_REF:0000117 qualifier: involved_in review: summary: 'Plausible non-core CHMP4C nuclear-envelope ESCRT context: nuclear membrane reassembly.' action: KEEP_AS_NON_CORE reason: Nuclear envelope sealing/reassembly is a supported ESCRT-III context, but it is secondary to the CHMP4C-specific abscission-checkpoint role. supported_by: - reference_id: PMID:26040712 supporting_text: ESCRT-III, VPS4 and spastin cooperate to coordinate nuclear envelope sealing and spindle disassembly - reference_id: PMID:26040713 supporting_text: ESCRT-III controls nuclear envelope reformation - term: id: GO:0031902 label: late endosome membrane evidence_type: IEA original_reference_id: GO_REF:0000044 qualifier: located_in review: summary: 'Plausible but non-core CHMP4C ESCRT/MVB context: late endosome membrane.' action: KEEP_AS_NON_CORE reason: CHMP4C belongs to the CHMP4/ESCRT-III family, but CHMP4C-specific evidence points most strongly to abscission-checkpoint regulation; MVB/endosomal sorting annotations are retained as non-core ESCRT-family context. supported_by: - reference_id: UniProt:Q96CF2 supporting_text: involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs - reference_id: PMID:18511562 supporting_text: The ESCRT pathway facilitates membrane fission events during enveloped virus budding, multivesicular body formation, and cytokinesis - reference_id: PMID:22422861 supporting_text: depletion of CHMP4B prevented MHC-I degradation, whereas depletion of CHMP4A or CHMP4C had little effect - reference_id: file:human/CHMP4C/CHMP4C-notes.md supporting_text: broad MVB cargo-degradation annotations for CHMP4C should be retained, at most, as non-core/over-annotated ESCRT-family context - term: id: GO:0032585 label: multivesicular body membrane evidence_type: IEA original_reference_id: GO_REF:0000117 qualifier: located_in review: summary: 'Plausible but non-core CHMP4C ESCRT/MVB context: multivesicular body membrane.' action: KEEP_AS_NON_CORE reason: CHMP4C belongs to the CHMP4/ESCRT-III family, but CHMP4C-specific evidence points most strongly to abscission-checkpoint regulation; MVB/endosomal sorting annotations are retained as non-core ESCRT-family context. supported_by: - reference_id: UniProt:Q96CF2 supporting_text: involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs - reference_id: PMID:18511562 supporting_text: The ESCRT pathway facilitates membrane fission events during enveloped virus budding, multivesicular body formation, and cytokinesis - reference_id: PMID:22422861 supporting_text: depletion of CHMP4B prevented MHC-I degradation, whereas depletion of CHMP4A or CHMP4C had little effect - reference_id: file:human/CHMP4C/CHMP4C-notes.md supporting_text: broad MVB cargo-degradation annotations for CHMP4C should be retained, at most, as non-core/over-annotated ESCRT-family context - term: id: GO:0036258 label: multivesicular body assembly evidence_type: IEA original_reference_id: GO_REF:0000117 qualifier: involved_in review: summary: 'Plausible but non-core CHMP4C ESCRT/MVB context: multivesicular body assembly.' action: KEEP_AS_NON_CORE reason: CHMP4C belongs to the CHMP4/ESCRT-III family, but CHMP4C-specific evidence points most strongly to abscission-checkpoint regulation; MVB/endosomal sorting annotations are retained as non-core ESCRT-family context. supported_by: - reference_id: UniProt:Q96CF2 supporting_text: involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs - reference_id: PMID:18511562 supporting_text: The ESCRT pathway facilitates membrane fission events during enveloped virus budding, multivesicular body formation, and cytokinesis - reference_id: PMID:22422861 supporting_text: depletion of CHMP4B prevented MHC-I degradation, whereas depletion of CHMP4A or CHMP4C had little effect - reference_id: file:human/CHMP4C/CHMP4C-notes.md supporting_text: broad MVB cargo-degradation annotations for CHMP4C should be retained, at most, as non-core/over-annotated ESCRT-family context - term: id: GO:0039702 label: viral budding via host ESCRT complex evidence_type: IEA original_reference_id: GO_REF:0000117 qualifier: involved_in review: summary: 'Likely paralog over-annotation for CHMP4C viral budding context: viral budding via host ESCRT complex.' action: MARK_AS_OVER_ANNOTATED reason: 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. supported_by: - reference_id: PMID:22422861 supporting_text: depletion of CHMP4A or CHMP4C did not inhibit HIV-1 release - reference_id: PMID:22422861 supporting_text: only depletion of CHMP4B inhibited this ESCRT-dependent process - reference_id: file:human/CHMP4C/CHMP4C-notes.md supporting_text: Viral budding annotations are also likely paralog over-annotations for CHMP4C - term: id: GO:0042803 label: protein homodimerization activity evidence_type: IEA original_reference_id: GO_REF:0000117 qualifier: enables review: summary: 'Over-annotated CHMP4C molecular-function annotation: protein homodimerization activity.' action: MARK_AS_OVER_ANNOTATED reason: '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.' supported_by: - reference_id: PMID:18511562 supporting_text: Bro1 domain of ALIX binds specifically to C-terminal residues of the human CHMP4 proteins (CHMP4A-C) - reference_id: PMID:36107470 supporting_text: CHMP4C performs a unique role in abscission checkpoint regulation - reference_id: file:human/CHMP4C/CHMP4C-notes.md supporting_text: Generic protein binding and homodimerization annotations are over-annotated. - term: id: GO:0043162 label: ubiquitin-dependent protein catabolic process via the multivesicular body sorting pathway evidence_type: IEA original_reference_id: GO_REF:0000117 qualifier: involved_in review: summary: 'Plausible but non-core CHMP4C ESCRT/MVB context: ubiquitin-dependent protein catabolic process via the multivesicular body sorting pathway.' action: KEEP_AS_NON_CORE reason: CHMP4C belongs to the CHMP4/ESCRT-III family, but CHMP4C-specific evidence points most strongly to abscission-checkpoint regulation; MVB/endosomal sorting annotations are retained as non-core ESCRT-family context. supported_by: - reference_id: UniProt:Q96CF2 supporting_text: involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs - reference_id: PMID:18511562 supporting_text: The ESCRT pathway facilitates membrane fission events during enveloped virus budding, multivesicular body formation, and cytokinesis - reference_id: PMID:22422861 supporting_text: depletion of CHMP4B prevented MHC-I degradation, whereas depletion of CHMP4A or CHMP4C had little effect - reference_id: file:human/CHMP4C/CHMP4C-notes.md supporting_text: broad MVB cargo-degradation annotations for CHMP4C should be retained, at most, as non-core/over-annotated ESCRT-family context - term: id: GO:0046761 label: viral budding from plasma membrane evidence_type: IEA original_reference_id: GO_REF:0000117 qualifier: involved_in review: summary: 'Likely paralog over-annotation for CHMP4C viral budding context: viral budding from plasma membrane.' action: MARK_AS_OVER_ANNOTATED reason: 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. supported_by: - reference_id: PMID:22422861 supporting_text: depletion of CHMP4A or CHMP4C did not inhibit HIV-1 release - reference_id: PMID:22422861 supporting_text: only depletion of CHMP4B inhibited this ESCRT-dependent process - reference_id: file:human/CHMP4C/CHMP4C-notes.md supporting_text: Viral budding annotations are also likely paralog over-annotations for CHMP4C - term: id: GO:0061952 label: midbody abscission evidence_type: IEA original_reference_id: GO_REF:0000117 qualifier: involved_in review: summary: 'Supported core CHMP4C abscission-checkpoint annotation: midbody abscission.' action: ACCEPT reason: CHMP4C is a specialized ESCRT-III regulatory subunit for Aurora B/NoCut abscission checkpoint control, delaying abscission through phosphorylation-dependent localization and ANCHR/VPS4 retention at the midbody. supported_by: - reference_id: UniProt:Q96CF2 supporting_text: component of the cytokinesis checkpoint - reference_id: UniProt:Q96CF2 supporting_text: retains abscission-competent VPS4 - reference_id: PMID:22422861 supporting_text: CHMP4C functioned in the Aurora B-dependent abscission checkpoint - reference_id: PMID:22422861 supporting_text: depletion of CHMP4C reduced abscission time by approximately 30 minutes - reference_id: PMID:22422861 supporting_text: CHMP4C depletion circumvents the NoCut abscission checkpoint - reference_id: PMID:24814515 supporting_text: In concert with CHMP4C, ANCHR associates with VPS4 at the midbody ring - reference_id: PMID:24814515 supporting_text: abscission checkpoint is mediated by ANCHR and CHMP4C through retention of VPS4 at the midbody ring - reference_id: PMID:22724069 supporting_text: Borealin interacts directly with the Snf7 components of ESCRT-III - reference_id: PMID:22724069 supporting_text: phosphorylates one of the three human Snf7 paralogues-CHMP4C - term: id: GO:0071985 label: multivesicular body sorting pathway evidence_type: IEA original_reference_id: GO_REF:0000117 qualifier: involved_in review: summary: 'Plausible but non-core CHMP4C ESCRT/MVB context: multivesicular body sorting pathway.' action: KEEP_AS_NON_CORE reason: CHMP4C belongs to the CHMP4/ESCRT-III family, but CHMP4C-specific evidence points most strongly to abscission-checkpoint regulation; MVB/endosomal sorting annotations are retained as non-core ESCRT-family context. supported_by: - reference_id: UniProt:Q96CF2 supporting_text: involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs - reference_id: PMID:18511562 supporting_text: The ESCRT pathway facilitates membrane fission events during enveloped virus budding, multivesicular body formation, and cytokinesis - reference_id: PMID:22422861 supporting_text: depletion of CHMP4B prevented MHC-I degradation, whereas depletion of CHMP4A or CHMP4C had little effect - reference_id: file:human/CHMP4C/CHMP4C-notes.md supporting_text: broad MVB cargo-degradation annotations for CHMP4C should be retained, at most, as non-core/over-annotated ESCRT-family context - term: id: GO:0090543 label: Flemming body evidence_type: IEA original_reference_id: GO_REF:0000044 qualifier: located_in review: summary: 'Supported core CHMP4C cytokinesis-checkpoint location: Flemming body.' action: ACCEPT reason: CHMP4C localizes to the midbody and Flemming body during late cytokinesis, with timing and localization tied to its Aurora B-dependent abscission-checkpoint function. supported_by: - reference_id: PMID:22422861 supporting_text: GFP-CHMP4C localized earlier to the midbody - reference_id: PMID:22422861 supporting_text: HA-CHMP4C localised to the Flemming-body in an INS-dependent manner - reference_id: PMID:22422861 supporting_text: Aurora B-dependent phosphorylation of S210 allows CHMP4C localization to the Flemming body - term: id: GO:0097352 label: autophagosome maturation evidence_type: IEA original_reference_id: GO_REF:0000117 qualifier: involved_in review: summary: 'Plausible PN-relevant but non-core CHMP4C autophagy/endolysosomal context: autophagosome maturation.' action: KEEP_AS_NON_CORE reason: The PN places CHMP4C in an ESCRT-III autophagophore closure bucket and ESCRT/MVB function supports autophagic clearance, but cached CHMP4C-specific papers do not directly test CHMP4C as the phagophore sealing effector. supported_by: - reference_id: PMID:17984323 supporting_text: Functional multivesicular bodies are required for autophagic clearance - reference_id: PMID:17984323 supporting_text: autophagic degradation is inhibited in cells depleted of ESCRT subunits - reference_id: file:human/CHMP4C/CHMP4C-notes.md supporting_text: the cached CHMP4C-specific papers do not directly assay CHMP4C as the phagophore sealing effector - term: id: GO:1901673 label: regulation of mitotic spindle assembly evidence_type: IEA original_reference_id: GO_REF:0000117 qualifier: involved_in review: summary: 'Plausible non-core CHMP4C centrosome/spindle/cell-cycle context: regulation of mitotic spindle assembly.' action: KEEP_AS_NON_CORE reason: ESCRT-III/VPS4 perturbation affects centrosome and spindle maintenance, but these broad cell-cycle annotations are secondary to CHMP4C abscission-checkpoint regulation. supported_by: - reference_id: PMID:20616062 supporting_text: depletion of individual ESCRT-III and VPS4 proteins also altered centrosome and spindle pole numbers - reference_id: PMID:20616062 supporting_text: ESCRT-III/VPS4 proteins function at centrosomes to help regulate their maintenance or proliferation and then at midbodies during abscission - term: id: GO:1902774 label: late endosome to lysosome transport evidence_type: IEA original_reference_id: GO_REF:0000117 qualifier: involved_in review: summary: 'Plausible but non-core CHMP4C ESCRT/MVB context: late endosome to lysosome transport.' action: KEEP_AS_NON_CORE reason: CHMP4C belongs to the CHMP4/ESCRT-III family, but CHMP4C-specific evidence points most strongly to abscission-checkpoint regulation; MVB/endosomal sorting annotations are retained as non-core ESCRT-family context. supported_by: - reference_id: UniProt:Q96CF2 supporting_text: involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs - reference_id: PMID:18511562 supporting_text: The ESCRT pathway facilitates membrane fission events during enveloped virus budding, multivesicular body formation, and cytokinesis - reference_id: PMID:22422861 supporting_text: depletion of CHMP4B prevented MHC-I degradation, whereas depletion of CHMP4A or CHMP4C had little effect - reference_id: file:human/CHMP4C/CHMP4C-notes.md supporting_text: broad MVB cargo-degradation annotations for CHMP4C should be retained, at most, as non-core/over-annotated ESCRT-family context - term: id: GO:1904930 label: amphisome membrane evidence_type: IEA original_reference_id: GO_REF:0000117 qualifier: located_in review: summary: 'Plausible PN-relevant but non-core CHMP4C autophagy/endolysosomal context: amphisome membrane.' action: KEEP_AS_NON_CORE reason: The PN places CHMP4C in an ESCRT-III autophagophore closure bucket and ESCRT/MVB function supports autophagic clearance, but cached CHMP4C-specific papers do not directly test CHMP4C as the phagophore sealing effector. supported_by: - reference_id: PMID:17984323 supporting_text: Functional multivesicular bodies are required for autophagic clearance - reference_id: PMID:17984323 supporting_text: autophagic degradation is inhibited in cells depleted of ESCRT subunits - reference_id: file:human/CHMP4C/CHMP4C-notes.md supporting_text: the cached CHMP4C-specific papers do not directly assay CHMP4C as the phagophore sealing effector - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:17711858 qualifier: enables review: summary: 'Over-annotated CHMP4C molecular-function annotation: protein binding.' action: MARK_AS_OVER_ANNOTATED reason: '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.' supported_by: - reference_id: PMID:18511562 supporting_text: Bro1 domain of ALIX binds specifically to C-terminal residues of the human CHMP4 proteins (CHMP4A-C) - reference_id: PMID:36107470 supporting_text: CHMP4C performs a unique role in abscission checkpoint regulation - reference_id: file:human/CHMP4C/CHMP4C-notes.md supporting_text: Generic protein binding and homodimerization annotations are over-annotated. - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:18511562 qualifier: enables review: summary: 'Over-annotated CHMP4C molecular-function annotation: protein binding.' action: MARK_AS_OVER_ANNOTATED reason: '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.' supported_by: - reference_id: PMID:18511562 supporting_text: Bro1 domain of ALIX binds specifically to C-terminal residues of the human CHMP4 proteins (CHMP4A-C) - reference_id: PMID:36107470 supporting_text: CHMP4C performs a unique role in abscission checkpoint regulation - reference_id: file:human/CHMP4C/CHMP4C-notes.md supporting_text: Generic protein binding and homodimerization annotations are over-annotated. - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:19302785 qualifier: enables review: summary: 'Over-annotated CHMP4C molecular-function annotation: protein binding.' action: MARK_AS_OVER_ANNOTATED reason: '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.' supported_by: - reference_id: PMID:18511562 supporting_text: Bro1 domain of ALIX binds specifically to C-terminal residues of the human CHMP4 proteins (CHMP4A-C) - reference_id: PMID:36107470 supporting_text: CHMP4C performs a unique role in abscission checkpoint regulation - reference_id: file:human/CHMP4C/CHMP4C-notes.md supporting_text: Generic protein binding and homodimerization annotations are over-annotated. - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:21988832 qualifier: enables review: summary: 'Over-annotated CHMP4C molecular-function annotation: protein binding.' action: MARK_AS_OVER_ANNOTATED reason: '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.' supported_by: - reference_id: PMID:18511562 supporting_text: Bro1 domain of ALIX binds specifically to C-terminal residues of the human CHMP4 proteins (CHMP4A-C) - reference_id: PMID:36107470 supporting_text: CHMP4C performs a unique role in abscission checkpoint regulation - reference_id: file:human/CHMP4C/CHMP4C-notes.md supporting_text: Generic protein binding and homodimerization annotations are over-annotated. - term: id: GO:0000421 label: autophagosome membrane evidence_type: IDA original_reference_id: PMID:17984323 qualifier: located_in review: summary: 'Plausible PN-relevant but non-core CHMP4C autophagy/endolysosomal context: autophagosome membrane.' action: KEEP_AS_NON_CORE reason: The PN places CHMP4C in an ESCRT-III autophagophore closure bucket and ESCRT/MVB function supports autophagic clearance, but cached CHMP4C-specific papers do not directly test CHMP4C as the phagophore sealing effector. supported_by: - reference_id: PMID:17984323 supporting_text: Functional multivesicular bodies are required for autophagic clearance - reference_id: PMID:17984323 supporting_text: autophagic degradation is inhibited in cells depleted of ESCRT subunits - reference_id: file:human/CHMP4C/CHMP4C-notes.md supporting_text: the cached CHMP4C-specific papers do not directly assay CHMP4C as the phagophore sealing effector - term: id: GO:0000776 label: kinetochore evidence_type: IDA original_reference_id: PMID:26040712 qualifier: located_in review: summary: 'Plausible non-core CHMP4C centrosome/spindle/cell-cycle context: kinetochore.' action: KEEP_AS_NON_CORE reason: ESCRT-III/VPS4 perturbation affects centrosome and spindle maintenance, but these broad cell-cycle annotations are secondary to CHMP4C abscission-checkpoint regulation. supported_by: - reference_id: PMID:20616062 supporting_text: depletion of individual ESCRT-III and VPS4 proteins also altered centrosome and spindle pole numbers - reference_id: PMID:20616062 supporting_text: ESCRT-III/VPS4 proteins function at centrosomes to help regulate their maintenance or proliferation and then at midbodies during abscission - term: id: GO:0000815 label: ESCRT III complex evidence_type: NAS original_reference_id: PMID:36107470 qualifier: part_of review: summary: 'Supported CHMP4C ESCRT-III complex membership annotation: ESCRT III complex.' action: ACCEPT reason: CHMP4C is a Snf7-family CHMP4 subunit of ESCRT-III; its most specific cellular function is checkpoint regulation, but complex membership is sound. supported_by: - reference_id: UniProt:Q96CF2 supporting_text: Probable core component of the endosomal sorting required for transport complex III (ESCRT-III) - reference_id: UniProt:Q96CF2 supporting_text: ESCRT-III proteins mostly dissociate from the invaginating membrane before the ILV is released - reference_id: PMID:18511562 supporting_text: Bro1 domain of ALIX binds specifically to C-terminal residues of the human CHMP4 proteins (CHMP4A-C) - reference_id: PMID:36107470 supporting_text: CHMP4C performs a unique role in abscission checkpoint regulation - reference_id: file:human/CHMP4C/CHMP4C-notes.md supporting_text: CHMP4C still has bona fide ESCRT-III context. - term: id: GO:0001778 label: plasma membrane repair evidence_type: IDA original_reference_id: PMID:24482116 qualifier: involved_in review: summary: Plausible non-core CHMP4C plasma-membrane repair ESCRT context. action: KEEP_AS_NON_CORE reason: Plasma membrane repair is a valid ESCRT output context, but the available CHMP4C-specific evidence points to abscission-checkpoint regulation rather than plasma repair as core function. supported_by: - reference_id: PMID:24482116 supporting_text: ESCRT proteins were recruited within seconds to plasma membrane wounds - reference_id: PMID:24482116 supporting_text: repair of certain wounds is ensured by ESCRT-mediated extracellular shedding of wounded portions - term: id: GO:0005643 label: nuclear pore evidence_type: IDA original_reference_id: PMID:26040713 qualifier: part_of review: summary: 'Plausible non-core CHMP4C nuclear-envelope ESCRT context: nuclear pore.' action: KEEP_AS_NON_CORE reason: Nuclear envelope sealing/reassembly is a supported ESCRT-III context, but it is secondary to the CHMP4C-specific abscission-checkpoint role. supported_by: - reference_id: PMID:26040712 supporting_text: ESCRT-III, VPS4 and spastin cooperate to coordinate nuclear envelope sealing and spindle disassembly - reference_id: PMID:26040713 supporting_text: ESCRT-III controls nuclear envelope reformation - term: id: GO:0005765 label: lysosomal membrane evidence_type: IDA original_reference_id: PMID:17984323 qualifier: located_in review: summary: 'Plausible PN-relevant but non-core CHMP4C autophagy/endolysosomal context: lysosomal membrane.' action: KEEP_AS_NON_CORE reason: The PN places CHMP4C in an ESCRT-III autophagophore closure bucket and ESCRT/MVB function supports autophagic clearance, but cached CHMP4C-specific papers do not directly test CHMP4C as the phagophore sealing effector. supported_by: - reference_id: PMID:17984323 supporting_text: Functional multivesicular bodies are required for autophagic clearance - reference_id: PMID:17984323 supporting_text: autophagic degradation is inhibited in cells depleted of ESCRT subunits - reference_id: file:human/CHMP4C/CHMP4C-notes.md supporting_text: the cached CHMP4C-specific papers do not directly assay CHMP4C as the phagophore sealing effector - term: id: GO:0005828 label: kinetochore microtubule evidence_type: IDA original_reference_id: PMID:26040712 qualifier: located_in review: summary: 'Plausible non-core CHMP4C centrosome/spindle/cell-cycle context: kinetochore microtubule.' action: KEEP_AS_NON_CORE reason: ESCRT-III/VPS4 perturbation affects centrosome and spindle maintenance, but these broad cell-cycle annotations are secondary to CHMP4C abscission-checkpoint regulation. supported_by: - reference_id: PMID:20616062 supporting_text: depletion of individual ESCRT-III and VPS4 proteins also altered centrosome and spindle pole numbers - reference_id: PMID:20616062 supporting_text: ESCRT-III/VPS4 proteins function at centrosomes to help regulate their maintenance or proliferation and then at midbodies during abscission - term: id: GO:0005886 label: plasma membrane evidence_type: IDA original_reference_id: PMID:24878737 qualifier: located_in review: summary: 'True or plausible broad CHMP4C location: plasma membrane.' action: KEEP_AS_NON_CORE reason: This location is compatible with CHMP4C cycling between cytosol and recruited ESCRT-III assemblies, but it is too broad to represent the core function by itself. supported_by: - reference_id: UniProt:Q96CF2 supporting_text: Cytoplasm. Cytosol - reference_id: UniProt:Q96CF2 supporting_text: Localizes to the midbody during late cytokinesis - term: id: GO:0006914 label: autophagy evidence_type: IMP original_reference_id: PMID:17984323 qualifier: involved_in review: summary: 'Plausible PN-relevant but non-core CHMP4C autophagy/endolysosomal context: autophagy.' action: KEEP_AS_NON_CORE reason: The PN places CHMP4C in an ESCRT-III autophagophore closure bucket and ESCRT/MVB function supports autophagic clearance, but cached CHMP4C-specific papers do not directly test CHMP4C as the phagophore sealing effector. supported_by: - reference_id: PMID:17984323 supporting_text: Functional multivesicular bodies are required for autophagic clearance - reference_id: PMID:17984323 supporting_text: autophagic degradation is inhibited in cells depleted of ESCRT subunits - reference_id: file:human/CHMP4C/CHMP4C-notes.md supporting_text: the cached CHMP4C-specific papers do not directly assay CHMP4C as the phagophore sealing effector - term: id: GO:0006997 label: nucleus organization evidence_type: IMP original_reference_id: PMID:20616062 qualifier: involved_in review: summary: 'Plausible non-core CHMP4C centrosome/spindle/cell-cycle context: nucleus organization.' action: KEEP_AS_NON_CORE reason: ESCRT-III/VPS4 perturbation affects centrosome and spindle maintenance, but these broad cell-cycle annotations are secondary to CHMP4C abscission-checkpoint regulation. supported_by: - reference_id: PMID:20616062 supporting_text: depletion of individual ESCRT-III and VPS4 proteins also altered centrosome and spindle pole numbers - reference_id: PMID:20616062 supporting_text: ESCRT-III/VPS4 proteins function at centrosomes to help regulate their maintenance or proliferation and then at midbodies during abscission - term: id: GO:0007080 label: mitotic metaphase chromosome alignment evidence_type: IMP original_reference_id: PMID:20616062 qualifier: involved_in review: summary: 'Plausible non-core CHMP4C centrosome/spindle/cell-cycle context: mitotic metaphase chromosome alignment.' action: KEEP_AS_NON_CORE reason: ESCRT-III/VPS4 perturbation affects centrosome and spindle maintenance, but these broad cell-cycle annotations are secondary to CHMP4C abscission-checkpoint regulation. supported_by: - reference_id: PMID:20616062 supporting_text: depletion of individual ESCRT-III and VPS4 proteins also altered centrosome and spindle pole numbers - reference_id: PMID:20616062 supporting_text: ESCRT-III/VPS4 proteins function at centrosomes to help regulate their maintenance or proliferation and then at midbodies during abscission - term: id: GO:0030496 label: midbody evidence_type: IDA original_reference_id: PMID:26040712 qualifier: located_in review: summary: 'Supported core CHMP4C cytokinesis-checkpoint location: midbody.' action: ACCEPT reason: CHMP4C localizes to the midbody and Flemming body during late cytokinesis, with timing and localization tied to its Aurora B-dependent abscission-checkpoint function. supported_by: - reference_id: PMID:22422861 supporting_text: GFP-CHMP4C localized earlier to the midbody - reference_id: PMID:22422861 supporting_text: HA-CHMP4C localised to the Flemming-body in an INS-dependent manner - reference_id: PMID:22422861 supporting_text: Aurora B-dependent phosphorylation of S210 allows CHMP4C localization to the Flemming body - term: id: GO:0031468 label: nuclear membrane reassembly evidence_type: IMP original_reference_id: PMID:26040713 qualifier: involved_in review: summary: 'Plausible non-core CHMP4C nuclear-envelope ESCRT context: nuclear membrane reassembly.' action: KEEP_AS_NON_CORE reason: Nuclear envelope sealing/reassembly is a supported ESCRT-III context, but it is secondary to the CHMP4C-specific abscission-checkpoint role. supported_by: - reference_id: PMID:26040712 supporting_text: ESCRT-III, VPS4 and spastin cooperate to coordinate nuclear envelope sealing and spindle disassembly - reference_id: PMID:26040713 supporting_text: ESCRT-III controls nuclear envelope reformation - term: id: GO:0032585 label: multivesicular body membrane evidence_type: IDA original_reference_id: PMID:16554368 qualifier: located_in review: summary: 'Plausible but non-core CHMP4C ESCRT/MVB context: multivesicular body membrane.' action: KEEP_AS_NON_CORE reason: CHMP4C belongs to the CHMP4/ESCRT-III family, but CHMP4C-specific evidence points most strongly to abscission-checkpoint regulation; MVB/endosomal sorting annotations are retained as non-core ESCRT-family context. supported_by: - reference_id: UniProt:Q96CF2 supporting_text: involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs - reference_id: PMID:18511562 supporting_text: The ESCRT pathway facilitates membrane fission events during enveloped virus budding, multivesicular body formation, and cytokinesis - reference_id: PMID:22422861 supporting_text: depletion of CHMP4B prevented MHC-I degradation, whereas depletion of CHMP4A or CHMP4C had little effect - reference_id: file:human/CHMP4C/CHMP4C-notes.md supporting_text: broad MVB cargo-degradation annotations for CHMP4C should be retained, at most, as non-core/over-annotated ESCRT-family context - term: id: GO:0036258 label: multivesicular body assembly evidence_type: NAS original_reference_id: PMID:16505166 qualifier: involved_in review: summary: 'Plausible but non-core CHMP4C ESCRT/MVB context: multivesicular body assembly.' action: KEEP_AS_NON_CORE reason: CHMP4C belongs to the CHMP4/ESCRT-III family, but CHMP4C-specific evidence points most strongly to abscission-checkpoint regulation; MVB/endosomal sorting annotations are retained as non-core ESCRT-family context. supported_by: - reference_id: UniProt:Q96CF2 supporting_text: involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs - reference_id: PMID:18511562 supporting_text: The ESCRT pathway facilitates membrane fission events during enveloped virus budding, multivesicular body formation, and cytokinesis - reference_id: PMID:22422861 supporting_text: depletion of CHMP4B prevented MHC-I degradation, whereas depletion of CHMP4A or CHMP4C had little effect - reference_id: file:human/CHMP4C/CHMP4C-notes.md supporting_text: broad MVB cargo-degradation annotations for CHMP4C should be retained, at most, as non-core/over-annotated ESCRT-family context - term: id: GO:0039702 label: viral budding via host ESCRT complex evidence_type: IDA original_reference_id: PMID:24878737 qualifier: involved_in review: summary: 'Likely paralog over-annotation for CHMP4C viral budding context: viral budding via host ESCRT complex.' action: MARK_AS_OVER_ANNOTATED reason: 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. supported_by: - reference_id: PMID:22422861 supporting_text: depletion of CHMP4A or CHMP4C did not inhibit HIV-1 release - reference_id: PMID:22422861 supporting_text: only depletion of CHMP4B inhibited this ESCRT-dependent process - reference_id: file:human/CHMP4C/CHMP4C-notes.md supporting_text: Viral budding annotations are also likely paralog over-annotations for CHMP4C - term: id: GO:0043162 label: ubiquitin-dependent protein catabolic process via the multivesicular body sorting pathway evidence_type: IDA original_reference_id: PMID:17984323 qualifier: involved_in review: summary: 'Plausible but non-core CHMP4C ESCRT/MVB context: ubiquitin-dependent protein catabolic process via the multivesicular body sorting pathway.' action: KEEP_AS_NON_CORE reason: CHMP4C belongs to the CHMP4/ESCRT-III family, but CHMP4C-specific evidence points most strongly to abscission-checkpoint regulation; MVB/endosomal sorting annotations are retained as non-core ESCRT-family context. supported_by: - reference_id: UniProt:Q96CF2 supporting_text: involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs - reference_id: PMID:18511562 supporting_text: The ESCRT pathway facilitates membrane fission events during enveloped virus budding, multivesicular body formation, and cytokinesis - reference_id: PMID:22422861 supporting_text: depletion of CHMP4B prevented MHC-I degradation, whereas depletion of CHMP4A or CHMP4C had little effect - reference_id: file:human/CHMP4C/CHMP4C-notes.md supporting_text: broad MVB cargo-degradation annotations for CHMP4C should be retained, at most, as non-core/over-annotated ESCRT-family context - term: id: GO:0046761 label: viral budding from plasma membrane evidence_type: IDA original_reference_id: PMID:24878737 qualifier: involved_in review: summary: 'Likely paralog over-annotation for CHMP4C viral budding context: viral budding from plasma membrane.' action: MARK_AS_OVER_ANNOTATED reason: 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. supported_by: - reference_id: PMID:22422861 supporting_text: depletion of CHMP4A or CHMP4C did not inhibit HIV-1 release - reference_id: PMID:22422861 supporting_text: only depletion of CHMP4B inhibited this ESCRT-dependent process - reference_id: file:human/CHMP4C/CHMP4C-notes.md supporting_text: Viral budding annotations are also likely paralog over-annotations for CHMP4C - term: id: GO:0051469 label: vesicle fusion with vacuole evidence_type: NAS original_reference_id: PMID:16505166 qualifier: involved_in review: summary: 'CHMP4C annotation should be replaced with a less over-specific ESCRT/MVB term: vesicle fusion with vacuole.' action: MODIFY reason: The evidence supports ESCRT/MVB trafficking context rather than CHMP4C acting as a vesicle-vacuole fusion factor. supported_by: - reference_id: UniProt:Q96CF2 supporting_text: involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs - reference_id: PMID:18511562 supporting_text: The ESCRT pathway facilitates membrane fission events during enveloped virus budding, multivesicular body formation, and cytokinesis - reference_id: PMID:22422861 supporting_text: depletion of CHMP4B prevented MHC-I degradation, whereas depletion of CHMP4A or CHMP4C had little effect - reference_id: file:human/CHMP4C/CHMP4C-notes.md supporting_text: broad MVB cargo-degradation annotations for CHMP4C should be retained, at most, as non-core/over-annotated ESCRT-family context proposed_replacement_terms: - id: GO:1902774 label: late endosome to lysosome transport - term: id: GO:0061763 label: multivesicular body-lysosome fusion evidence_type: NAS original_reference_id: PMID:16505166 qualifier: involved_in review: summary: 'CHMP4C annotation should be replaced with a less over-specific ESCRT/MVB term: multivesicular body-lysosome fusion.' action: MODIFY reason: The evidence supports late endosome-to-lysosome/endolysosomal transport context rather than CHMP4C as a direct MVB-lysosome fusion factor. supported_by: - reference_id: UniProt:Q96CF2 supporting_text: involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs - reference_id: PMID:18511562 supporting_text: The ESCRT pathway facilitates membrane fission events during enveloped virus budding, multivesicular body formation, and cytokinesis - reference_id: PMID:22422861 supporting_text: depletion of CHMP4B prevented MHC-I degradation, whereas depletion of CHMP4A or CHMP4C had little effect - reference_id: file:human/CHMP4C/CHMP4C-notes.md supporting_text: broad MVB cargo-degradation annotations for CHMP4C should be retained, at most, as non-core/over-annotated ESCRT-family context proposed_replacement_terms: - id: GO:1902774 label: late endosome to lysosome transport - term: id: GO:0061952 label: midbody abscission evidence_type: IMP original_reference_id: PMID:20616062 qualifier: involved_in review: summary: 'Supported core CHMP4C abscission-checkpoint annotation: midbody abscission.' action: ACCEPT reason: CHMP4C is a specialized ESCRT-III regulatory subunit for Aurora B/NoCut abscission checkpoint control, delaying abscission through phosphorylation-dependent localization and ANCHR/VPS4 retention at the midbody. supported_by: - reference_id: UniProt:Q96CF2 supporting_text: component of the cytokinesis checkpoint - reference_id: UniProt:Q96CF2 supporting_text: retains abscission-competent VPS4 - reference_id: PMID:22422861 supporting_text: CHMP4C functioned in the Aurora B-dependent abscission checkpoint - reference_id: PMID:22422861 supporting_text: depletion of CHMP4C reduced abscission time by approximately 30 minutes - reference_id: PMID:22422861 supporting_text: CHMP4C depletion circumvents the NoCut abscission checkpoint - reference_id: PMID:24814515 supporting_text: In concert with CHMP4C, ANCHR associates with VPS4 at the midbody ring - reference_id: PMID:24814515 supporting_text: abscission checkpoint is mediated by ANCHR and CHMP4C through retention of VPS4 at the midbody ring - reference_id: PMID:22724069 supporting_text: Borealin interacts directly with the Snf7 components of ESCRT-III - reference_id: PMID:22724069 supporting_text: phosphorylates one of the three human Snf7 paralogues-CHMP4C - term: id: GO:0071985 label: multivesicular body sorting pathway evidence_type: IDA original_reference_id: PMID:16554368 qualifier: involved_in review: summary: 'Plausible but non-core CHMP4C ESCRT/MVB context: multivesicular body sorting pathway.' action: KEEP_AS_NON_CORE reason: CHMP4C belongs to the CHMP4/ESCRT-III family, but CHMP4C-specific evidence points most strongly to abscission-checkpoint regulation; MVB/endosomal sorting annotations are retained as non-core ESCRT-family context. supported_by: - reference_id: UniProt:Q96CF2 supporting_text: involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs - reference_id: PMID:18511562 supporting_text: The ESCRT pathway facilitates membrane fission events during enveloped virus budding, multivesicular body formation, and cytokinesis - reference_id: PMID:22422861 supporting_text: depletion of CHMP4B prevented MHC-I degradation, whereas depletion of CHMP4A or CHMP4C had little effect - reference_id: file:human/CHMP4C/CHMP4C-notes.md supporting_text: broad MVB cargo-degradation annotations for CHMP4C should be retained, at most, as non-core/over-annotated ESCRT-family context - term: id: GO:0090148 label: membrane fission evidence_type: NAS original_reference_id: PMID:19234443 qualifier: involved_in review: summary: 'Plausible but non-core CHMP4C ESCRT/MVB context: membrane fission.' action: KEEP_AS_NON_CORE reason: CHMP4C belongs to the CHMP4/ESCRT-III family, but CHMP4C-specific evidence points most strongly to abscission-checkpoint regulation; MVB/endosomal sorting annotations are retained as non-core ESCRT-family context. supported_by: - reference_id: UniProt:Q96CF2 supporting_text: involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs - reference_id: PMID:18511562 supporting_text: The ESCRT pathway facilitates membrane fission events during enveloped virus budding, multivesicular body formation, and cytokinesis - reference_id: PMID:22422861 supporting_text: depletion of CHMP4B prevented MHC-I degradation, whereas depletion of CHMP4A or CHMP4C had little effect - reference_id: file:human/CHMP4C/CHMP4C-notes.md supporting_text: broad MVB cargo-degradation annotations for CHMP4C should be retained, at most, as non-core/over-annotated ESCRT-family context - term: id: GO:0097352 label: autophagosome maturation evidence_type: IMP original_reference_id: PMID:17984323 qualifier: involved_in review: summary: 'Plausible PN-relevant but non-core CHMP4C autophagy/endolysosomal context: autophagosome maturation.' action: KEEP_AS_NON_CORE reason: The PN places CHMP4C in an ESCRT-III autophagophore closure bucket and ESCRT/MVB function supports autophagic clearance, but cached CHMP4C-specific papers do not directly test CHMP4C as the phagophore sealing effector. supported_by: - reference_id: PMID:17984323 supporting_text: Functional multivesicular bodies are required for autophagic clearance - reference_id: PMID:17984323 supporting_text: autophagic degradation is inhibited in cells depleted of ESCRT subunits - reference_id: file:human/CHMP4C/CHMP4C-notes.md supporting_text: the cached CHMP4C-specific papers do not directly assay CHMP4C as the phagophore sealing effector - term: id: GO:1901673 label: regulation of mitotic spindle assembly evidence_type: IMP original_reference_id: PMID:20616062 qualifier: involved_in review: summary: 'Plausible non-core CHMP4C centrosome/spindle/cell-cycle context: regulation of mitotic spindle assembly.' action: KEEP_AS_NON_CORE reason: ESCRT-III/VPS4 perturbation affects centrosome and spindle maintenance, but these broad cell-cycle annotations are secondary to CHMP4C abscission-checkpoint regulation. supported_by: - reference_id: PMID:20616062 supporting_text: depletion of individual ESCRT-III and VPS4 proteins also altered centrosome and spindle pole numbers - reference_id: PMID:20616062 supporting_text: ESCRT-III/VPS4 proteins function at centrosomes to help regulate their maintenance or proliferation and then at midbodies during abscission - term: id: GO:1902774 label: late endosome to lysosome transport evidence_type: IMP original_reference_id: PMID:17984323 qualifier: involved_in review: summary: 'Plausible but non-core CHMP4C ESCRT/MVB context: late endosome to lysosome transport.' action: KEEP_AS_NON_CORE reason: CHMP4C belongs to the CHMP4/ESCRT-III family, but CHMP4C-specific evidence points most strongly to abscission-checkpoint regulation; MVB/endosomal sorting annotations are retained as non-core ESCRT-family context. supported_by: - reference_id: UniProt:Q96CF2 supporting_text: involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs - reference_id: PMID:18511562 supporting_text: The ESCRT pathway facilitates membrane fission events during enveloped virus budding, multivesicular body formation, and cytokinesis - reference_id: PMID:22422861 supporting_text: depletion of CHMP4B prevented MHC-I degradation, whereas depletion of CHMP4A or CHMP4C had little effect - reference_id: file:human/CHMP4C/CHMP4C-notes.md supporting_text: broad MVB cargo-degradation annotations for CHMP4C should be retained, at most, as non-core/over-annotated ESCRT-family context - term: id: GO:1904930 label: amphisome membrane evidence_type: IDA original_reference_id: PMID:17984323 qualifier: located_in review: summary: 'Plausible PN-relevant but non-core CHMP4C autophagy/endolysosomal context: amphisome membrane.' action: KEEP_AS_NON_CORE reason: The PN places CHMP4C in an ESCRT-III autophagophore closure bucket and ESCRT/MVB function supports autophagic clearance, but cached CHMP4C-specific papers do not directly test CHMP4C as the phagophore sealing effector. supported_by: - reference_id: PMID:17984323 supporting_text: Functional multivesicular bodies are required for autophagic clearance - reference_id: PMID:17984323 supporting_text: autophagic degradation is inhibited in cells depleted of ESCRT subunits - reference_id: file:human/CHMP4C/CHMP4C-notes.md supporting_text: the cached CHMP4C-specific papers do not directly assay CHMP4C as the phagophore sealing effector - term: id: GO:0061952 label: midbody abscission evidence_type: IMP original_reference_id: PMID:22422861 qualifier: involved_in review: summary: 'Supported core CHMP4C abscission-checkpoint annotation: midbody abscission.' action: ACCEPT reason: CHMP4C is a specialized ESCRT-III regulatory subunit for Aurora B/NoCut abscission checkpoint control, delaying abscission through phosphorylation-dependent localization and ANCHR/VPS4 retention at the midbody. supported_by: - reference_id: UniProt:Q96CF2 supporting_text: component of the cytokinesis checkpoint - reference_id: UniProt:Q96CF2 supporting_text: retains abscission-competent VPS4 - reference_id: PMID:22422861 supporting_text: CHMP4C functioned in the Aurora B-dependent abscission checkpoint - reference_id: PMID:22422861 supporting_text: depletion of CHMP4C reduced abscission time by approximately 30 minutes - reference_id: PMID:22422861 supporting_text: CHMP4C depletion circumvents the NoCut abscission checkpoint - reference_id: PMID:24814515 supporting_text: In concert with CHMP4C, ANCHR associates with VPS4 at the midbody ring - reference_id: PMID:24814515 supporting_text: abscission checkpoint is mediated by ANCHR and CHMP4C through retention of VPS4 at the midbody ring - reference_id: PMID:22724069 supporting_text: Borealin interacts directly with the Snf7 components of ESCRT-III - reference_id: PMID:22724069 supporting_text: phosphorylates one of the three human Snf7 paralogues-CHMP4C - term: id: GO:0061952 label: midbody abscission evidence_type: IMP original_reference_id: PMID:24814515 qualifier: involved_in review: summary: 'Supported core CHMP4C abscission-checkpoint annotation: midbody abscission.' action: ACCEPT reason: CHMP4C is a specialized ESCRT-III regulatory subunit for Aurora B/NoCut abscission checkpoint control, delaying abscission through phosphorylation-dependent localization and ANCHR/VPS4 retention at the midbody. supported_by: - reference_id: UniProt:Q96CF2 supporting_text: component of the cytokinesis checkpoint - reference_id: UniProt:Q96CF2 supporting_text: retains abscission-competent VPS4 - reference_id: PMID:22422861 supporting_text: CHMP4C functioned in the Aurora B-dependent abscission checkpoint - reference_id: PMID:22422861 supporting_text: depletion of CHMP4C reduced abscission time by approximately 30 minutes - reference_id: PMID:22422861 supporting_text: CHMP4C depletion circumvents the NoCut abscission checkpoint - reference_id: PMID:24814515 supporting_text: In concert with CHMP4C, ANCHR associates with VPS4 at the midbody ring - reference_id: PMID:24814515 supporting_text: abscission checkpoint is mediated by ANCHR and CHMP4C through retention of VPS4 at the midbody ring - reference_id: PMID:22724069 supporting_text: Borealin interacts directly with the Snf7 components of ESCRT-III - reference_id: PMID:22724069 supporting_text: phosphorylates one of the three human Snf7 paralogues-CHMP4C - term: id: GO:0046761 label: viral budding from plasma membrane evidence_type: IMP original_reference_id: PMID:14505570 qualifier: involved_in review: summary: 'Likely paralog over-annotation for CHMP4C viral budding context: viral budding from plasma membrane.' action: MARK_AS_OVER_ANNOTATED reason: 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. supported_by: - reference_id: PMID:22422861 supporting_text: depletion of CHMP4A or CHMP4C did not inhibit HIV-1 release - reference_id: PMID:22422861 supporting_text: only depletion of CHMP4B inhibited this ESCRT-dependent process - reference_id: file:human/CHMP4C/CHMP4C-notes.md supporting_text: Viral budding annotations are also likely paralog over-annotations for CHMP4C - term: id: GO:0044878 label: mitotic cytokinesis checkpoint signaling evidence_type: IMP original_reference_id: PMID:22422861 qualifier: involved_in review: summary: 'Supported core CHMP4C abscission-checkpoint annotation: mitotic cytokinesis checkpoint signaling.' action: ACCEPT reason: CHMP4C is a specialized ESCRT-III regulatory subunit for Aurora B/NoCut abscission checkpoint control, delaying abscission through phosphorylation-dependent localization and ANCHR/VPS4 retention at the midbody. supported_by: - reference_id: UniProt:Q96CF2 supporting_text: component of the cytokinesis checkpoint - reference_id: UniProt:Q96CF2 supporting_text: retains abscission-competent VPS4 - reference_id: PMID:22422861 supporting_text: CHMP4C functioned in the Aurora B-dependent abscission checkpoint - reference_id: PMID:22422861 supporting_text: depletion of CHMP4C reduced abscission time by approximately 30 minutes - reference_id: PMID:22422861 supporting_text: CHMP4C depletion circumvents the NoCut abscission checkpoint - reference_id: PMID:24814515 supporting_text: In concert with CHMP4C, ANCHR associates with VPS4 at the midbody ring - reference_id: PMID:24814515 supporting_text: abscission checkpoint is mediated by ANCHR and CHMP4C through retention of VPS4 at the midbody ring - reference_id: PMID:22724069 supporting_text: Borealin interacts directly with the Snf7 components of ESCRT-III - reference_id: PMID:22724069 supporting_text: phosphorylates one of the three human Snf7 paralogues-CHMP4C - term: id: GO:0044878 label: mitotic cytokinesis checkpoint signaling evidence_type: IMP original_reference_id: PMID:24814515 qualifier: involved_in review: summary: 'Supported core CHMP4C abscission-checkpoint annotation: mitotic cytokinesis checkpoint signaling.' action: ACCEPT reason: CHMP4C is a specialized ESCRT-III regulatory subunit for Aurora B/NoCut abscission checkpoint control, delaying abscission through phosphorylation-dependent localization and ANCHR/VPS4 retention at the midbody. supported_by: - reference_id: UniProt:Q96CF2 supporting_text: component of the cytokinesis checkpoint - reference_id: UniProt:Q96CF2 supporting_text: retains abscission-competent VPS4 - reference_id: PMID:22422861 supporting_text: CHMP4C functioned in the Aurora B-dependent abscission checkpoint - reference_id: PMID:22422861 supporting_text: depletion of CHMP4C reduced abscission time by approximately 30 minutes - reference_id: PMID:22422861 supporting_text: CHMP4C depletion circumvents the NoCut abscission checkpoint - reference_id: PMID:24814515 supporting_text: In concert with CHMP4C, ANCHR associates with VPS4 at the midbody ring - reference_id: PMID:24814515 supporting_text: abscission checkpoint is mediated by ANCHR and CHMP4C through retention of VPS4 at the midbody ring - reference_id: PMID:22724069 supporting_text: Borealin interacts directly with the Snf7 components of ESCRT-III - reference_id: PMID:22724069 supporting_text: phosphorylates one of the three human Snf7 paralogues-CHMP4C - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:18641129 qualifier: enables review: summary: 'Over-annotated CHMP4C molecular-function annotation: protein binding.' action: MARK_AS_OVER_ANNOTATED reason: '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.' supported_by: - reference_id: PMID:18511562 supporting_text: Bro1 domain of ALIX binds specifically to C-terminal residues of the human CHMP4 proteins (CHMP4A-C) - reference_id: PMID:36107470 supporting_text: CHMP4C performs a unique role in abscission checkpoint regulation - reference_id: file:human/CHMP4C/CHMP4C-notes.md supporting_text: Generic protein binding and homodimerization annotations are over-annotated. - term: id: GO:0016236 label: macroautophagy evidence_type: TAS original_reference_id: PMID:20588296 qualifier: involved_in review: summary: 'Plausible PN-relevant but non-core CHMP4C autophagy/endolysosomal context: macroautophagy.' action: KEEP_AS_NON_CORE reason: The PN places CHMP4C in an ESCRT-III autophagophore closure bucket and ESCRT/MVB function supports autophagic clearance, but cached CHMP4C-specific papers do not directly test CHMP4C as the phagophore sealing effector. supported_by: - reference_id: PMID:17984323 supporting_text: Functional multivesicular bodies are required for autophagic clearance - reference_id: PMID:17984323 supporting_text: autophagic degradation is inhibited in cells depleted of ESCRT subunits - reference_id: file:human/CHMP4C/CHMP4C-notes.md supporting_text: the cached CHMP4C-specific papers do not directly assay CHMP4C as the phagophore sealing effector - term: id: GO:0000815 label: ESCRT III complex evidence_type: TAS original_reference_id: PMID:20588296 qualifier: part_of review: summary: 'Supported CHMP4C ESCRT-III complex membership annotation: ESCRT III complex.' action: ACCEPT reason: CHMP4C is a Snf7-family CHMP4 subunit of ESCRT-III; its most specific cellular function is checkpoint regulation, but complex membership is sound. supported_by: - reference_id: UniProt:Q96CF2 supporting_text: Probable core component of the endosomal sorting required for transport complex III (ESCRT-III) - reference_id: UniProt:Q96CF2 supporting_text: ESCRT-III proteins mostly dissociate from the invaginating membrane before the ILV is released - reference_id: PMID:18511562 supporting_text: Bro1 domain of ALIX binds specifically to C-terminal residues of the human CHMP4 proteins (CHMP4A-C) - reference_id: PMID:36107470 supporting_text: CHMP4C performs a unique role in abscission checkpoint regulation - reference_id: file:human/CHMP4C/CHMP4C-notes.md supporting_text: CHMP4C still has bona fide ESCRT-III context. - term: id: GO:0036258 label: multivesicular body assembly evidence_type: TAS original_reference_id: PMID:20588296 qualifier: involved_in review: summary: 'Plausible but non-core CHMP4C ESCRT/MVB context: multivesicular body assembly.' action: KEEP_AS_NON_CORE reason: CHMP4C belongs to the CHMP4/ESCRT-III family, but CHMP4C-specific evidence points most strongly to abscission-checkpoint regulation; MVB/endosomal sorting annotations are retained as non-core ESCRT-family context. supported_by: - reference_id: UniProt:Q96CF2 supporting_text: involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs - reference_id: PMID:18511562 supporting_text: The ESCRT pathway facilitates membrane fission events during enveloped virus budding, multivesicular body formation, and cytokinesis - reference_id: PMID:22422861 supporting_text: depletion of CHMP4B prevented MHC-I degradation, whereas depletion of CHMP4A or CHMP4C had little effect - reference_id: file:human/CHMP4C/CHMP4C-notes.md supporting_text: broad MVB cargo-degradation annotations for CHMP4C should be retained, at most, as non-core/over-annotated ESCRT-family context - term: id: GO:0039702 label: viral budding via host ESCRT complex evidence_type: TAS original_reference_id: PMID:20588296 qualifier: involved_in review: summary: 'Likely paralog over-annotation for CHMP4C viral budding context: viral budding via host ESCRT complex.' action: MARK_AS_OVER_ANNOTATED reason: 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. supported_by: - reference_id: PMID:22422861 supporting_text: depletion of CHMP4A or CHMP4C did not inhibit HIV-1 release - reference_id: PMID:22422861 supporting_text: only depletion of CHMP4B inhibited this ESCRT-dependent process - reference_id: file:human/CHMP4C/CHMP4C-notes.md supporting_text: Viral budding annotations are also likely paralog over-annotations for CHMP4C - term: id: GO:0010824 label: regulation of centrosome duplication evidence_type: IMP original_reference_id: PMID:20616062 qualifier: involved_in review: summary: 'Plausible non-core CHMP4C centrosome/spindle/cell-cycle context: regulation of centrosome duplication.' action: KEEP_AS_NON_CORE reason: ESCRT-III/VPS4 perturbation affects centrosome and spindle maintenance, but these broad cell-cycle annotations are secondary to CHMP4C abscission-checkpoint regulation. supported_by: - reference_id: PMID:20616062 supporting_text: depletion of individual ESCRT-III and VPS4 proteins also altered centrosome and spindle pole numbers - reference_id: PMID:20616062 supporting_text: ESCRT-III/VPS4 proteins function at centrosomes to help regulate their maintenance or proliferation and then at midbodies during abscission - term: id: GO:0090611 label: obsolete ubiquitin-independent protein catabolic process via the multivesicular body sorting pathway evidence_type: IMP original_reference_id: PMID:22547407 qualifier: involved_in review: summary: 'CHMP4C annotation should be replaced with a less over-specific ESCRT/MVB term: obsolete ubiquitin-independent protein catabolic process via the multivesicular body sorting pathway.' action: MODIFY reason: This obsolete ubiquitin-independent catabolic process term should be replaced by the non-obsolete MVB sorting pathway term. supported_by: - reference_id: PMID:22547407 supporting_text: PAR1 sorted to ILVs of MVBs through an ESCRT-III-dependent pathway independent of ubiquitination - reference_id: PMID:22547407 supporting_text: ALIX binds to a YPX3L motif of PAR1 and recruits ESCRT-III to mediate MVB/lysosomal sorting proposed_replacement_terms: - id: GO:0071985 label: multivesicular body sorting pathway - term: id: GO:0032466 label: negative regulation of cytokinesis evidence_type: IMP original_reference_id: PMID:22422861 qualifier: involved_in review: summary: 'Supported core CHMP4C abscission-checkpoint annotation: negative regulation of cytokinesis.' action: ACCEPT reason: CHMP4C is a specialized ESCRT-III regulatory subunit for Aurora B/NoCut abscission checkpoint control, delaying abscission through phosphorylation-dependent localization and ANCHR/VPS4 retention at the midbody. supported_by: - reference_id: UniProt:Q96CF2 supporting_text: component of the cytokinesis checkpoint - reference_id: UniProt:Q96CF2 supporting_text: retains abscission-competent VPS4 - reference_id: PMID:22422861 supporting_text: CHMP4C functioned in the Aurora B-dependent abscission checkpoint - reference_id: PMID:22422861 supporting_text: depletion of CHMP4C reduced abscission time by approximately 30 minutes - reference_id: PMID:22422861 supporting_text: CHMP4C depletion circumvents the NoCut abscission checkpoint - reference_id: PMID:24814515 supporting_text: In concert with CHMP4C, ANCHR associates with VPS4 at the midbody ring - reference_id: PMID:24814515 supporting_text: abscission checkpoint is mediated by ANCHR and CHMP4C through retention of VPS4 at the midbody ring - reference_id: PMID:22724069 supporting_text: Borealin interacts directly with the Snf7 components of ESCRT-III - reference_id: PMID:22724069 supporting_text: phosphorylates one of the three human Snf7 paralogues-CHMP4C - term: id: GO:0032466 label: negative regulation of cytokinesis evidence_type: IMP original_reference_id: PMID:24814515 qualifier: involved_in review: summary: 'Supported core CHMP4C abscission-checkpoint annotation: negative regulation of cytokinesis.' action: ACCEPT reason: CHMP4C is a specialized ESCRT-III regulatory subunit for Aurora B/NoCut abscission checkpoint control, delaying abscission through phosphorylation-dependent localization and ANCHR/VPS4 retention at the midbody. supported_by: - reference_id: UniProt:Q96CF2 supporting_text: component of the cytokinesis checkpoint - reference_id: UniProt:Q96CF2 supporting_text: retains abscission-competent VPS4 - reference_id: PMID:22422861 supporting_text: CHMP4C functioned in the Aurora B-dependent abscission checkpoint - reference_id: PMID:22422861 supporting_text: depletion of CHMP4C reduced abscission time by approximately 30 minutes - reference_id: PMID:22422861 supporting_text: CHMP4C depletion circumvents the NoCut abscission checkpoint - reference_id: PMID:24814515 supporting_text: In concert with CHMP4C, ANCHR associates with VPS4 at the midbody ring - reference_id: PMID:24814515 supporting_text: abscission checkpoint is mediated by ANCHR and CHMP4C through retention of VPS4 at the midbody ring - reference_id: PMID:22724069 supporting_text: Borealin interacts directly with the Snf7 components of ESCRT-III - reference_id: PMID:22724069 supporting_text: phosphorylates one of the three human Snf7 paralogues-CHMP4C - term: id: GO:0090543 label: Flemming body evidence_type: IDA original_reference_id: PMID:22422861 qualifier: located_in review: summary: 'Supported core CHMP4C cytokinesis-checkpoint location: Flemming body.' action: ACCEPT reason: CHMP4C localizes to the midbody and Flemming body during late cytokinesis, with timing and localization tied to its Aurora B-dependent abscission-checkpoint function. supported_by: - reference_id: PMID:22422861 supporting_text: GFP-CHMP4C localized earlier to the midbody - reference_id: PMID:22422861 supporting_text: HA-CHMP4C localised to the Flemming-body in an INS-dependent manner - reference_id: PMID:22422861 supporting_text: Aurora B-dependent phosphorylation of S210 allows CHMP4C localization to the Flemming body - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:14519844 qualifier: enables review: summary: 'Over-annotated CHMP4C molecular-function annotation: protein binding.' action: MARK_AS_OVER_ANNOTATED reason: '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.' supported_by: - reference_id: PMID:18511562 supporting_text: Bro1 domain of ALIX binds specifically to C-terminal residues of the human CHMP4 proteins (CHMP4A-C) - reference_id: PMID:36107470 supporting_text: CHMP4C performs a unique role in abscission checkpoint regulation - reference_id: file:human/CHMP4C/CHMP4C-notes.md supporting_text: Generic protein binding and homodimerization annotations are over-annotated. - term: id: GO:0042803 label: protein homodimerization activity evidence_type: IPI original_reference_id: PMID:14519844 qualifier: enables review: summary: 'Over-annotated CHMP4C molecular-function annotation: protein homodimerization activity.' action: MARK_AS_OVER_ANNOTATED reason: '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.' supported_by: - reference_id: PMID:18511562 supporting_text: Bro1 domain of ALIX binds specifically to C-terminal residues of the human CHMP4 proteins (CHMP4A-C) - reference_id: PMID:36107470 supporting_text: CHMP4C performs a unique role in abscission checkpoint regulation - reference_id: file:human/CHMP4C/CHMP4C-notes.md supporting_text: Generic protein binding and homodimerization annotations are over-annotated. - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:14505570 qualifier: enables review: summary: 'Over-annotated CHMP4C molecular-function annotation: protein binding.' action: MARK_AS_OVER_ANNOTATED reason: '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.' supported_by: - reference_id: PMID:18511562 supporting_text: Bro1 domain of ALIX binds specifically to C-terminal residues of the human CHMP4 proteins (CHMP4A-C) - reference_id: PMID:36107470 supporting_text: CHMP4C performs a unique role in abscission checkpoint regulation - reference_id: file:human/CHMP4C/CHMP4C-notes.md supporting_text: Generic protein binding and homodimerization annotations are over-annotated. - term: id: GO:0042803 label: protein homodimerization activity evidence_type: IPI original_reference_id: PMID:14505570 qualifier: enables review: summary: 'Over-annotated CHMP4C molecular-function annotation: protein homodimerization activity.' action: MARK_AS_OVER_ANNOTATED reason: '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.' supported_by: - reference_id: PMID:18511562 supporting_text: Bro1 domain of ALIX binds specifically to C-terminal residues of the human CHMP4 proteins (CHMP4A-C) - reference_id: PMID:36107470 supporting_text: CHMP4C performs a unique role in abscission checkpoint regulation - reference_id: file:human/CHMP4C/CHMP4C-notes.md supporting_text: Generic protein binding and homodimerization annotations are over-annotated. - term: id: GO:0005829 label: cytosol evidence_type: TAS original_reference_id: Reactome:R-HSA-3159232 qualifier: located_in review: summary: 'True or plausible broad CHMP4C location: cytosol.' action: KEEP_AS_NON_CORE reason: This location is compatible with CHMP4C cycling between cytosol and recruited ESCRT-III assemblies, but it is too broad to represent the core function by itself. supported_by: - reference_id: UniProt:Q96CF2 supporting_text: Cytoplasm. Cytosol - reference_id: UniProt:Q96CF2 supporting_text: Localizes to the midbody during late cytokinesis - term: id: GO:0005829 label: cytosol evidence_type: TAS original_reference_id: Reactome:R-HSA-917693 qualifier: located_in review: summary: 'True or plausible broad CHMP4C location: cytosol.' action: KEEP_AS_NON_CORE reason: This location is compatible with CHMP4C cycling between cytosol and recruited ESCRT-III assemblies, but it is too broad to represent the core function by itself. supported_by: - reference_id: UniProt:Q96CF2 supporting_text: Cytoplasm. Cytosol - reference_id: UniProt:Q96CF2 supporting_text: Localizes to the midbody during late cytokinesis - term: id: GO:0005829 label: cytosol evidence_type: TAS original_reference_id: Reactome:R-HSA-917700 qualifier: located_in review: summary: 'True or plausible broad CHMP4C location: cytosol.' action: KEEP_AS_NON_CORE reason: This location is compatible with CHMP4C cycling between cytosol and recruited ESCRT-III assemblies, but it is too broad to represent the core function by itself. supported_by: - reference_id: UniProt:Q96CF2 supporting_text: Cytoplasm. Cytosol - reference_id: UniProt:Q96CF2 supporting_text: Localizes to the midbody during late cytokinesis - term: id: GO:0005829 label: cytosol evidence_type: TAS original_reference_id: Reactome:R-HSA-9668389 qualifier: located_in review: summary: 'True or plausible broad CHMP4C location: cytosol.' action: KEEP_AS_NON_CORE reason: This location is compatible with CHMP4C cycling between cytosol and recruited ESCRT-III assemblies, but it is too broad to represent the core function by itself. supported_by: - reference_id: UniProt:Q96CF2 supporting_text: Cytoplasm. Cytosol - reference_id: UniProt:Q96CF2 supporting_text: Localizes to the midbody during late cytokinesis - term: id: GO:0005829 label: cytosol evidence_type: TAS original_reference_id: Reactome:R-HSA-9668395 qualifier: located_in review: summary: 'True or plausible broad CHMP4C location: cytosol.' action: KEEP_AS_NON_CORE reason: This location is compatible with CHMP4C cycling between cytosol and recruited ESCRT-III assemblies, but it is too broad to represent the core function by itself. supported_by: - reference_id: UniProt:Q96CF2 supporting_text: Cytoplasm. Cytosol - reference_id: UniProt:Q96CF2 supporting_text: Localizes to the midbody during late cytokinesis - term: id: GO:0005829 label: cytosol evidence_type: TAS original_reference_id: Reactome:R-HSA-9668398 qualifier: located_in review: summary: 'True or plausible broad CHMP4C location: cytosol.' action: KEEP_AS_NON_CORE reason: This location is compatible with CHMP4C cycling between cytosol and recruited ESCRT-III assemblies, but it is too broad to represent the core function by itself. supported_by: - reference_id: UniProt:Q96CF2 supporting_text: Cytoplasm. Cytosol - reference_id: UniProt:Q96CF2 supporting_text: Localizes to the midbody during late cytokinesis - term: id: GO:0005829 label: cytosol evidence_type: TAS original_reference_id: Reactome:R-HSA-9668405 qualifier: located_in review: summary: 'True or plausible broad CHMP4C location: cytosol.' action: KEEP_AS_NON_CORE reason: This location is compatible with CHMP4C cycling between cytosol and recruited ESCRT-III assemblies, but it is too broad to represent the core function by itself. supported_by: - reference_id: UniProt:Q96CF2 supporting_text: Cytoplasm. Cytosol - reference_id: UniProt:Q96CF2 supporting_text: Localizes to the midbody during late cytokinesis - term: id: GO:0005829 label: cytosol evidence_type: TAS original_reference_id: Reactome:R-HSA-9668415 qualifier: located_in review: summary: 'True or plausible broad CHMP4C location: cytosol.' action: KEEP_AS_NON_CORE reason: This location is compatible with CHMP4C cycling between cytosol and recruited ESCRT-III assemblies, but it is too broad to represent the core function by itself. supported_by: - reference_id: UniProt:Q96CF2 supporting_text: Cytoplasm. Cytosol - reference_id: UniProt:Q96CF2 supporting_text: Localizes to the midbody during late cytokinesis - term: id: GO:0005829 label: cytosol evidence_type: TAS original_reference_id: Reactome:R-HSA-9668419 qualifier: located_in review: summary: 'True or plausible broad CHMP4C location: cytosol.' action: KEEP_AS_NON_CORE reason: This location is compatible with CHMP4C cycling between cytosol and recruited ESCRT-III assemblies, but it is too broad to represent the core function by itself. supported_by: - reference_id: UniProt:Q96CF2 supporting_text: Cytoplasm. Cytosol - reference_id: UniProt:Q96CF2 supporting_text: Localizes to the midbody during late cytokinesis - term: id: GO:0030496 label: midbody evidence_type: IDA original_reference_id: PMID:22724069 qualifier: located_in review: summary: 'Supported core CHMP4C cytokinesis-checkpoint location: midbody.' action: ACCEPT reason: CHMP4C localizes to the midbody and Flemming body during late cytokinesis, with timing and localization tied to its Aurora B-dependent abscission-checkpoint function. supported_by: - reference_id: PMID:22422861 supporting_text: GFP-CHMP4C localized earlier to the midbody - reference_id: PMID:22422861 supporting_text: HA-CHMP4C localised to the Flemming-body in an INS-dependent manner - reference_id: PMID:22422861 supporting_text: Aurora B-dependent phosphorylation of S210 allows CHMP4C localization to the Flemming body references: - id: GO_REF:0000002 title: Gene Ontology annotation through association of InterPro records with GO terms findings: [] - id: GO_REF:0000033 title: Annotation inferences using phylogenetic trees findings: [] - id: GO_REF:0000044 title: Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular Location vocabulary mapping, accompanied by conservative changes to GO terms applied by UniProt findings: [] - id: GO_REF:0000117 title: Electronic Gene Ontology annotations created by ARBA machine learning models findings: [] - id: PMID:14505570 title: The protein network of HIV budding. findings: [] - id: PMID:14519844 title: Divergent retroviral late-budding domains recruit vacuolar protein sorting factors by using alternative adaptor proteins. findings: [] - id: PMID:16505166 title: Recycling of ESCRTs by the AAA-ATPase Vps4 is regulated by a conserved VSL region in Vta1. findings: [] - id: PMID:16554368 title: The ESCRT-III subunit hVps24 is required for degradation but not silencing of the epidermal growth factor receptor. findings: [] - id: PMID:17711858 title: The MIT domain of UBPY constitutes a CHMP binding and endosomal localization signal required for efficient epidermal growth factor receptor degradation. findings: [] - id: PMID:17984323 title: Functional multivesicular bodies are required for autophagic clearance of protein aggregates associated with neurodegenerative disease. findings: [] - id: PMID:18511562 title: ALIX-CHMP4 interactions in the human ESCRT pathway. findings: - statement: ALIX binds C-terminal residues of human CHMP4A-C, supporting CHMP4C ESCRT-III/Bro1-domain interaction context. - id: PMID:18641129 title: Differential requirements for Alix and ESCRT-III in cytokinesis and HIV-1 release. findings: [] - id: PMID:19234443 title: Membrane scission by the ESCRT-III complex. findings: [] - id: PMID:19302785 title: Ab initio protein modelling reveals novel human MIT domains. findings: [] - id: PMID:20588296 title: 'Membrane budding and scission by the ESCRT machinery: it''s all in the neck.' findings: [] - id: PMID:20616062 title: Human ESCRT-III and VPS4 proteins are required for centrosome and spindle maintenance. findings: [] - id: PMID:21988832 title: Toward an understanding of the protein interaction network of the human liver. findings: [] - id: PMID:22422861 title: ESCRT-III governs the Aurora B-mediated abscission checkpoint through CHMP4C. findings: - statement: CHMP4C is a human ESCRT-III subunit that regulates Aurora B-dependent NoCut abscission checkpoint timing and differs functionally from CHMP4B. - id: PMID:22547407 title: ALIX binds a YPX(3)L motif of the GPCR PAR1 and mediates ubiquitin-independent ESCRT-III/MVB sorting. findings: [] - id: PMID:22724069 title: The chromosomal passenger complex controls the function of endosomal sorting complex required for transport-III Snf7 proteins during cytokinesis. findings: - statement: Borealin/CPC interacts with Snf7/CHMP4 proteins and Aurora B phosphorylates CHMP4C to regulate cytokinesis. - id: PMID:24482116 title: ESCRT machinery is required for plasma membrane repair. findings: [] - id: PMID:24814515 title: ANCHR mediates Aurora-B-dependent abscission checkpoint control through retention of VPS4. findings: - statement: ANCHR/ZFYVE19 works with CHMP4C to retain VPS4 at the midbody ring during Aurora B-dependent checkpoint activation. - id: PMID:24878737 title: Structure of cellular ESCRT-III spirals and their relationship to HIV budding. findings: [] - id: PMID:26040712 title: Spastin and ESCRT-III coordinate mitotic spindle disassembly and nuclear envelope sealing. findings: [] - id: PMID:26040713 title: ESCRT-III controls nuclear envelope reformation. findings: [] - id: PMID:36107470 title: Comprehensive analysis of the human ESCRT-III-MIT domain interactome reveals new cofactors for cytokinetic abscission. findings: - statement: The ESCRT-III-MIT interactome study highlights CHMP4C unique checkpoint specialization and distinct C-terminal binding behavior. - id: Reactome:R-HSA-3159232 title: Recruitment Of HIV Virion Budding Machinery findings: [] - id: Reactome:R-HSA-917693 title: ESCRT Disassembly findings: [] - id: Reactome:R-HSA-917700 title: MVB Vesicle Formation findings: [] - id: Reactome:R-HSA-9668389 title: VPS4 binds ESCRT-III assemblies at nuclear envelope (NE) fenestrations findings: [] - id: Reactome:R-HSA-9668395 title: CHMP7 binds CC2D1B findings: [] - id: Reactome:R-HSA-9668398 title: CHMP7 binds CHMP4B, which recruits other subunits of the ESCRT-III complex findings: [] - id: Reactome:R-HSA-9668405 title: SPAST (spastin) binds the IST1 subunit of ESCRT-III at the sites of microtubule attachment to chromatin findings: [] - id: Reactome:R-HSA-9668415 title: VPS4 mediates disassembly of ESCRTIII subunits to promote sealing of holes in the nuclear envelope findings: [] - id: Reactome:R-HSA-9668419 title: SPAST (spastin) mediates the severing of microtubules at chromosome attachment sites findings: [] - id: file:human/CHMP4C/CHMP4C-notes.md title: Local curation notes for CHMP4C findings: - statement: Local synthesis identifies Aurora B/NoCut abscission checkpoint regulation as the CHMP4C core function and treats autophagy/MVB annotations as non-core ESCRT-family context. core_functions: - description: CHMP4C is a specialized ESCRT-III regulatory subunit for the Aurora B/NoCut abscission checkpoint. Aurora B-phosphorylated CHMP4C localizes to the midbody/Flemming body, engages CPC/Borealin and ANCHR/ZFYVE19, and retains VPS4 at the midbody ring to delay abscission until checkpoint signaling is relieved. in_complex: id: GO:0000815 label: ESCRT III complex directly_involved_in: - id: GO:0044878 label: mitotic cytokinesis checkpoint signaling - id: GO:0032466 label: negative regulation of cytokinesis - id: GO:0061952 label: midbody abscission locations: - id: GO:0090543 label: Flemming body - id: GO:0030496 label: midbody supported_by: - reference_id: UniProt:Q96CF2 supporting_text: component of the cytokinesis checkpoint - reference_id: UniProt:Q96CF2 supporting_text: retains abscission-competent VPS4 - reference_id: PMID:22422861 supporting_text: CHMP4C functioned in the Aurora B-dependent abscission checkpoint - reference_id: PMID:22422861 supporting_text: depletion of CHMP4C reduced abscission time by approximately 30 minutes - reference_id: PMID:22422861 supporting_text: CHMP4C depletion circumvents the NoCut abscission checkpoint - reference_id: PMID:24814515 supporting_text: In concert with CHMP4C, ANCHR associates with VPS4 at the midbody ring - reference_id: PMID:24814515 supporting_text: abscission checkpoint is mediated by ANCHR and CHMP4C through retention of VPS4 at the midbody ring - reference_id: PMID:22724069 supporting_text: Borealin interacts directly with the Snf7 components of ESCRT-III - reference_id: PMID:22724069 supporting_text: phosphorylates one of the three human Snf7 paralogues-CHMP4C - reference_id: PMID:22422861 supporting_text: GFP-CHMP4C localized earlier to the midbody - reference_id: PMID:22422861 supporting_text: HA-CHMP4C localised to the Flemming-body in an INS-dependent manner - reference_id: PMID:22422861 supporting_text: Aurora B-dependent phosphorylation of S210 allows CHMP4C localization to the Flemming body proposed_new_terms: [] suggested_questions: - question: Which ESCRT-III/autophagophore closure assays directly implicate CHMP4C, rather than CHMP4C being included by CHMP4-family or ESCRT-III component membership? - question: Should GO annotations for CHMP4C distinguish checkpoint-regulatory abscission roles from CHMP4B-like execution roles in MVB cargo degradation and HIV release? - question: Does CHMP4C phosphorylation state alter its ESCRT-III polymerization or partner recruitment in endosomal and autophagy contexts, or only at the cytokinetic midbody? suggested_experiments: - description: Use endogenous CHMP4C tagging and acute CHMP4C depletion/rescue in starvation-induced autophagy and mitophagy assays that monitor phagophore closure directly. hypothesis: If CHMP4C is a direct autophagophore sealing subunit, it should be recruited to unsealed autophagosomes and rescue should require its ESCRT-III core and regulatory tail. - description: Compare CHMP4A, CHMP4B, and CHMP4C depletion/rescue in MVB cargo degradation, HIV budding, abscission execution, and NoCut checkpoint activation using matched endogenous expression systems. hypothesis: CHMP4C will preferentially rescue checkpoint timing rather than CHMP4B-like MVB/HIV/cytokinesis execution phenotypes. - description: Test Aurora B phospho-site mutants and ANCHR-binding perturbations for effects on CHMP4C polymerization, VPS4 retention, and midbody-to-abscission-zone relocalization. hypothesis: CHMP4C phosphorylation controls checkpoint-mediated VPS4 retention and delayed abscission rather than simply controlling midbody recruitment.