id: Q9BY43 gene_symbol: CHMP4A product_type: PROTEIN status: COMPLETE taxon: id: NCBITaxon:9606 label: Homo sapiens description: CHMP4A encodes a Snf7-family core subunit of ESCRT-III. Its best-supported function is non-enzymatic ESCRT-III polymerization on endosomal/MVB and related membranes, where CHMP4A-containing filaments bend membranes and support reverse-topology budding/fission for intraluminal vesicle formation, MVB cargo sorting, and downstream endolysosomal degradation. CHMP4A also participates in autophagy/autophagosome contexts, plasma membrane repair, cytokinetic abscission, nuclear envelope repair, and viral budding as topologically related ESCRT output contexts, but those should not obscure the core ESCRT-III membrane-remodeling role. alternative_products: - name: '1' id: Q9BY43-1 - name: '2' id: Q9BY43-2 sequence_note: VSP_056264 existing_annotations: - term: id: GO:0005635 label: nuclear envelope evidence_type: IBA original_reference_id: GO_REF:0000033 qualifier: is_active_in review: summary: 'True or plausible non-core CHMP4A ESCRT context: nuclear envelope.' action: KEEP_AS_NON_CORE reason: Nuclear envelope or nuclear pore repair/reassembly is a supported ESCRT-III context but is secondary to CHMP4A core ESCRT-III membrane-remodeling function. supported_by: - reference_id: PMID:26040713 supporting_text: ESCRT-III controls nuclear envelope reformation - reference_id: UniProt:Q9BY43 supporting_text: Probable core component of the endosomal sorting required for transport complex III (ESCRT-III) - reference_id: UniProt:Q9BY43 supporting_text: involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs - term: id: GO:0031468 label: nuclear membrane reassembly evidence_type: IBA original_reference_id: GO_REF:0000033 qualifier: involved_in review: summary: 'True or plausible non-core CHMP4A ESCRT context: nuclear membrane reassembly.' action: KEEP_AS_NON_CORE reason: Nuclear envelope or nuclear pore repair/reassembly is a supported ESCRT-III context but is secondary to CHMP4A core ESCRT-III membrane-remodeling function. supported_by: - reference_id: PMID:26040713 supporting_text: ESCRT-III controls nuclear envelope reformation - reference_id: UniProt:Q9BY43 supporting_text: Probable core component of the endosomal sorting required for transport complex III (ESCRT-III) - reference_id: UniProt:Q9BY43 supporting_text: involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs - term: id: GO:0000815 label: ESCRT III complex evidence_type: IBA original_reference_id: GO_REF:0000033 qualifier: part_of review: summary: 'Supported core CHMP4A ESCRT-III/MVB membrane-remodeling annotation: ESCRT III complex.' action: ACCEPT reason: CHMP4A is a core ESCRT-III/Snf7-family subunit that polymerizes on endosomal and MVB membranes to promote membrane budding/fission and MVB cargo sorting. supported_by: - reference_id: UniProt:Q9BY43 supporting_text: Probable core component of the endosomal sorting required for transport complex III (ESCRT-III) - reference_id: UniProt:Q9BY43 supporting_text: involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs - reference_id: UniProt:Q9BY43 supporting_text: believed to mediate the necessary vesicle extrusion and/or membrane fission activities - reference_id: PMID:18209100 supporting_text: form novel membrane-attached filaments that can promote or stabilize negative curvature and outward budding - reference_id: PMID:19234443 supporting_text: ESCRT-III has the instrinsic ability to drive the scission of membrane necks - reference_id: PMID:18209100 supporting_text: ESCRT-III polymers delineate and help generate the luminal vesicles of multivesicular bodies - reference_id: PMID:18209100 supporting_text: Multivesicular bodies (MVBs) are mid-stage endosomes that contain intraluminal vesicles - reference_id: UniProt:Q9BY43 supporting_text: Cytoplasmic vesicle membrane. Late endosome membrane - reference_id: UniProt:Q9BY43 supporting_text: Membrane-associated - 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 non-core CHMP4A ESCRT context: cytoplasmic side of plasma membrane.' action: KEEP_AS_NON_CORE reason: This location or output context is supported or plausible for CHMP4A but is broad or secondary relative to its core ESCRT-III MVB/endosomal membrane-remodeling role. supported_by: - reference_id: UniProt:Q9BY43 supporting_text: believed to mediate the necessary vesicle extrusion and/or membrane fission activities - reference_id: PMID:18209100 supporting_text: form novel membrane-attached filaments that can promote or stabilize negative curvature and outward budding - reference_id: PMID:19234443 supporting_text: ESCRT-III has the instrinsic ability to drive the scission of membrane necks - reference_id: UniProt:Q9BY43 supporting_text: Cytoplasmic vesicle membrane. Late endosome membrane - reference_id: UniProt:Q9BY43 supporting_text: Membrane-associated - 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: 'Supported core CHMP4A ESCRT-III/MVB membrane-remodeling annotation: late endosome to vacuole transport via multivesicular body sorting pathway.' action: ACCEPT reason: CHMP4A is a core ESCRT-III/Snf7-family subunit that polymerizes on endosomal and MVB membranes to promote membrane budding/fission and MVB cargo sorting. supported_by: - reference_id: UniProt:Q9BY43 supporting_text: Probable core component of the endosomal sorting required for transport complex III (ESCRT-III) - reference_id: UniProt:Q9BY43 supporting_text: involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs - reference_id: UniProt:Q9BY43 supporting_text: believed to mediate the necessary vesicle extrusion and/or membrane fission activities - reference_id: PMID:18209100 supporting_text: form novel membrane-attached filaments that can promote or stabilize negative curvature and outward budding - reference_id: PMID:19234443 supporting_text: ESCRT-III has the instrinsic ability to drive the scission of membrane necks - reference_id: PMID:18209100 supporting_text: ESCRT-III polymers delineate and help generate the luminal vesicles of multivesicular bodies - reference_id: PMID:18209100 supporting_text: Multivesicular bodies (MVBs) are mid-stage endosomes that contain intraluminal vesicles - reference_id: UniProt:Q9BY43 supporting_text: Cytoplasmic vesicle membrane. Late endosome membrane - reference_id: UniProt:Q9BY43 supporting_text: Membrane-associated - term: id: GO:0000776 label: kinetochore evidence_type: IEA original_reference_id: GO_REF:0000117 qualifier: located_in review: summary: 'True or plausible non-core CHMP4A ESCRT context: kinetochore.' action: KEEP_AS_NON_CORE reason: Cytokinesis/midbody and spindle annotations are supported ESCRT output contexts, but they are not the central endolysosomal/proteostasis function emphasized for CHMP4A. supported_by: - reference_id: PMID:22724069 supporting_text: Borealin interacts directly with the Snf7 components of ESCRT-III - reference_id: PMID:22724069 supporting_text: controls abscission timing through inhibition of ESCRT-III Snf7 polymerization - reference_id: UniProt:Q9BY43 supporting_text: Probable core component of the endosomal sorting required for transport complex III (ESCRT-III) - reference_id: UniProt:Q9BY43 supporting_text: involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs - term: id: GO:0001778 label: plasma membrane repair evidence_type: IEA original_reference_id: GO_REF:0000117 qualifier: involved_in review: summary: 'True or plausible non-core CHMP4A ESCRT context: plasma membrane repair.' action: KEEP_AS_NON_CORE reason: Plasma membrane repair is a valid ESCRT output context, but the core CHMP4A function remains ESCRT-III membrane remodeling in endosomal/MVB and related compartments. 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 - reference_id: UniProt:Q9BY43 supporting_text: Probable core component of the endosomal sorting required for transport complex III (ESCRT-III) - reference_id: UniProt:Q9BY43 supporting_text: involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs - term: id: GO:0005643 label: nuclear pore evidence_type: IEA original_reference_id: GO_REF:0000117 qualifier: part_of review: summary: 'True or plausible non-core CHMP4A ESCRT context: nuclear pore.' action: KEEP_AS_NON_CORE reason: Nuclear envelope or nuclear pore repair/reassembly is a supported ESCRT-III context but is secondary to CHMP4A core ESCRT-III membrane-remodeling function. supported_by: - reference_id: PMID:26040713 supporting_text: ESCRT-III controls nuclear envelope reformation - reference_id: UniProt:Q9BY43 supporting_text: Probable core component of the endosomal sorting required for transport complex III (ESCRT-III) - reference_id: UniProt:Q9BY43 supporting_text: involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs - term: id: GO:0005765 label: lysosomal membrane evidence_type: IEA original_reference_id: GO_REF:0000117 qualifier: located_in review: summary: 'Supported PN-relevant autophagy/endolysosomal CHMP4A context: lysosomal membrane.' action: ACCEPT reason: CHMP4A/Snf7-1 depletion causes autophagosome accumulation in human neurons, and ESCRT/MVB function is required for autophagic degradation; this supports retaining autophagy and autophagosome-context annotations without claiming CHMP4A alone was directly assayed as the phagophore-sealing effector. supported_by: - reference_id: PMID:21975012 supporting_text: SiRNA knockdown of hSnf7-1 in human neurons leads to autophagosome accumulation - reference_id: PMID:17984323 supporting_text: Functional multivesicular bodies are required for autophagic clearance - reference_id: UniProt:Q9BY43 supporting_text: Probable core component of the endosomal sorting required for transport complex III (ESCRT-III) - reference_id: UniProt:Q9BY43 supporting_text: involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs - term: id: GO:0005828 label: kinetochore microtubule evidence_type: IEA original_reference_id: GO_REF:0000117 qualifier: located_in review: summary: 'True or plausible non-core CHMP4A ESCRT context: kinetochore microtubule.' action: KEEP_AS_NON_CORE reason: Cytokinesis/midbody and spindle annotations are supported ESCRT output contexts, but they are not the central endolysosomal/proteostasis function emphasized for CHMP4A. supported_by: - reference_id: PMID:22724069 supporting_text: Borealin interacts directly with the Snf7 components of ESCRT-III - reference_id: PMID:22724069 supporting_text: controls abscission timing through inhibition of ESCRT-III Snf7 polymerization - reference_id: UniProt:Q9BY43 supporting_text: Probable core component of the endosomal sorting required for transport complex III (ESCRT-III) - reference_id: UniProt:Q9BY43 supporting_text: involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs - term: id: GO:0007034 label: vacuolar transport evidence_type: IEA original_reference_id: GO_REF:0000002 qualifier: involved_in review: summary: The broad vacuolar transport label is less precise than CHMP4A MVB/endosomal sorting function. action: MODIFY reason: CHMP4A is best represented by ESCRT-III-mediated MVB sorting and ILV/membrane fission, not generic vacuolar transport. supported_by: - reference_id: UniProt:Q9BY43 supporting_text: Probable core component of the endosomal sorting required for transport complex III (ESCRT-III) - reference_id: UniProt:Q9BY43 supporting_text: involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs - reference_id: UniProt:Q9BY43 supporting_text: believed to mediate the necessary vesicle extrusion and/or membrane fission activities - reference_id: PMID:18209100 supporting_text: form novel membrane-attached filaments that can promote or stabilize negative curvature and outward budding - reference_id: PMID:19234443 supporting_text: ESCRT-III has the instrinsic ability to drive the scission of membrane necks 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: 'True or plausible non-core CHMP4A ESCRT context: mitotic metaphase chromosome alignment.' action: KEEP_AS_NON_CORE reason: Cytokinesis/midbody and spindle annotations are supported ESCRT output contexts, but they are not the central endolysosomal/proteostasis function emphasized for CHMP4A. supported_by: - reference_id: PMID:22724069 supporting_text: Borealin interacts directly with the Snf7 components of ESCRT-III - reference_id: PMID:22724069 supporting_text: controls abscission timing through inhibition of ESCRT-III Snf7 polymerization - reference_id: UniProt:Q9BY43 supporting_text: Probable core component of the endosomal sorting required for transport complex III (ESCRT-III) - reference_id: UniProt:Q9BY43 supporting_text: involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs - term: id: GO:0030496 label: midbody evidence_type: IEA original_reference_id: GO_REF:0000117 qualifier: located_in review: summary: 'True or plausible non-core CHMP4A ESCRT context: midbody.' action: KEEP_AS_NON_CORE reason: Cytokinesis/midbody and spindle annotations are supported ESCRT output contexts, but they are not the central endolysosomal/proteostasis function emphasized for CHMP4A. supported_by: - reference_id: PMID:22724069 supporting_text: Borealin interacts directly with the Snf7 components of ESCRT-III - reference_id: PMID:22724069 supporting_text: controls abscission timing through inhibition of ESCRT-III Snf7 polymerization - reference_id: UniProt:Q9BY43 supporting_text: Probable core component of the endosomal sorting required for transport complex III (ESCRT-III) - reference_id: UniProt:Q9BY43 supporting_text: involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs - term: id: GO:0030659 label: cytoplasmic vesicle membrane evidence_type: IEA original_reference_id: GO_REF:0000044 qualifier: located_in review: summary: 'Supported core CHMP4A ESCRT-III/MVB membrane-remodeling annotation: cytoplasmic vesicle membrane.' action: ACCEPT reason: CHMP4A is a core ESCRT-III/Snf7-family subunit that polymerizes on endosomal and MVB membranes to promote membrane budding/fission and MVB cargo sorting. supported_by: - reference_id: UniProt:Q9BY43 supporting_text: Cytoplasmic vesicle membrane. Late endosome membrane - reference_id: UniProt:Q9BY43 supporting_text: Membrane-associated - reference_id: PMID:18209100 supporting_text: ESCRT-III polymers delineate and help generate the luminal vesicles of multivesicular bodies - reference_id: PMID:18209100 supporting_text: Multivesicular bodies (MVBs) are mid-stage endosomes that contain intraluminal vesicles - term: id: GO:0031468 label: nuclear membrane reassembly evidence_type: IEA original_reference_id: GO_REF:0000117 qualifier: involved_in review: summary: 'True or plausible non-core CHMP4A ESCRT context: nuclear membrane reassembly.' action: KEEP_AS_NON_CORE reason: Nuclear envelope or nuclear pore repair/reassembly is a supported ESCRT-III context but is secondary to CHMP4A core ESCRT-III membrane-remodeling function. supported_by: - reference_id: PMID:26040713 supporting_text: ESCRT-III controls nuclear envelope reformation - reference_id: UniProt:Q9BY43 supporting_text: Probable core component of the endosomal sorting required for transport complex III (ESCRT-III) - reference_id: UniProt:Q9BY43 supporting_text: involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs - term: id: GO:0031902 label: late endosome membrane evidence_type: IEA original_reference_id: GO_REF:0000044 qualifier: located_in review: summary: 'Supported core CHMP4A ESCRT-III/MVB membrane-remodeling annotation: late endosome membrane.' action: ACCEPT reason: CHMP4A is a core ESCRT-III/Snf7-family subunit that polymerizes on endosomal and MVB membranes to promote membrane budding/fission and MVB cargo sorting. supported_by: - reference_id: UniProt:Q9BY43 supporting_text: Cytoplasmic vesicle membrane. Late endosome membrane - reference_id: UniProt:Q9BY43 supporting_text: Membrane-associated - reference_id: PMID:18209100 supporting_text: ESCRT-III polymers delineate and help generate the luminal vesicles of multivesicular bodies - reference_id: PMID:18209100 supporting_text: Multivesicular bodies (MVBs) are mid-stage endosomes that contain intraluminal vesicles - term: id: GO:0032585 label: multivesicular body membrane evidence_type: IEA original_reference_id: GO_REF:0000117 qualifier: located_in review: summary: 'Supported core CHMP4A ESCRT-III/MVB membrane-remodeling annotation: multivesicular body membrane.' action: ACCEPT reason: CHMP4A is a core ESCRT-III/Snf7-family subunit that polymerizes on endosomal and MVB membranes to promote membrane budding/fission and MVB cargo sorting. supported_by: - reference_id: UniProt:Q9BY43 supporting_text: Cytoplasmic vesicle membrane. Late endosome membrane - reference_id: UniProt:Q9BY43 supporting_text: Membrane-associated - reference_id: PMID:18209100 supporting_text: ESCRT-III polymers delineate and help generate the luminal vesicles of multivesicular bodies - reference_id: PMID:18209100 supporting_text: Multivesicular bodies (MVBs) are mid-stage endosomes that contain intraluminal vesicles - term: id: GO:0036258 label: multivesicular body assembly evidence_type: IEA original_reference_id: GO_REF:0000117 qualifier: involved_in review: summary: 'Supported core CHMP4A ESCRT-III/MVB membrane-remodeling annotation: multivesicular body assembly.' action: ACCEPT reason: CHMP4A is a core ESCRT-III/Snf7-family subunit that polymerizes on endosomal and MVB membranes to promote membrane budding/fission and MVB cargo sorting. supported_by: - reference_id: UniProt:Q9BY43 supporting_text: Probable core component of the endosomal sorting required for transport complex III (ESCRT-III) - reference_id: UniProt:Q9BY43 supporting_text: involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs - reference_id: UniProt:Q9BY43 supporting_text: believed to mediate the necessary vesicle extrusion and/or membrane fission activities - reference_id: PMID:18209100 supporting_text: form novel membrane-attached filaments that can promote or stabilize negative curvature and outward budding - reference_id: PMID:19234443 supporting_text: ESCRT-III has the instrinsic ability to drive the scission of membrane necks - reference_id: PMID:18209100 supporting_text: ESCRT-III polymers delineate and help generate the luminal vesicles of multivesicular bodies - reference_id: PMID:18209100 supporting_text: Multivesicular bodies (MVBs) are mid-stage endosomes that contain intraluminal vesicles - reference_id: UniProt:Q9BY43 supporting_text: Cytoplasmic vesicle membrane. Late endosome membrane - reference_id: UniProt:Q9BY43 supporting_text: Membrane-associated - 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: 'True or plausible non-core CHMP4A ESCRT context: viral budding via host ESCRT complex.' action: KEEP_AS_NON_CORE reason: Viral budding is directly supported as ESCRT hijacking but is not an endogenous core CHMP4A proteostasis function. supported_by: - reference_id: PMID:18511562 supporting_text: ALIX protein must bind and recruit CHMP4 subunits of the ESCRT-III complex - reference_id: PMID:24878737 supporting_text: Structure of cellular ESCRT-III spirals and their relationship to HIV budding - reference_id: UniProt:Q9BY43 supporting_text: Probable core component of the endosomal sorting required for transport complex III (ESCRT-III) - reference_id: UniProt:Q9BY43 supporting_text: involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs - term: id: GO:0042803 label: protein homodimerization activity evidence_type: IEA original_reference_id: GO_REF:0000117 qualifier: enables review: summary: protein homodimerization activity captures CHMP4A self-association but is less accurate than ESCRT-III polymerization and membrane bending. action: MODIFY reason: CHMP4A forms curved ESCRT-III filaments/polymers that bend membranes; homodimer or identical-protein binding terms are weaker molecular descriptions. supported_by: - reference_id: UniProt:Q9BY43 supporting_text: Probable core component of the endosomal sorting required for transport complex III (ESCRT-III) - reference_id: UniProt:Q9BY43 supporting_text: involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs - reference_id: UniProt:Q9BY43 supporting_text: believed to mediate the necessary vesicle extrusion and/or membrane fission activities - reference_id: PMID:18209100 supporting_text: form novel membrane-attached filaments that can promote or stabilize negative curvature and outward budding - reference_id: PMID:19234443 supporting_text: ESCRT-III has the instrinsic ability to drive the scission of membrane necks proposed_replacement_terms: - id: GO:0051258 label: protein polymerization - id: GO:0180020 label: membrane bending activity - 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: 'Supported core CHMP4A ESCRT-III/MVB membrane-remodeling annotation: ubiquitin-dependent protein catabolic process via the multivesicular body sorting pathway.' action: ACCEPT reason: CHMP4A is a core ESCRT-III/Snf7-family subunit that polymerizes on endosomal and MVB membranes to promote membrane budding/fission and MVB cargo sorting. supported_by: - reference_id: UniProt:Q9BY43 supporting_text: Probable core component of the endosomal sorting required for transport complex III (ESCRT-III) - reference_id: UniProt:Q9BY43 supporting_text: involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs - reference_id: UniProt:Q9BY43 supporting_text: believed to mediate the necessary vesicle extrusion and/or membrane fission activities - reference_id: PMID:18209100 supporting_text: form novel membrane-attached filaments that can promote or stabilize negative curvature and outward budding - reference_id: PMID:19234443 supporting_text: ESCRT-III has the instrinsic ability to drive the scission of membrane necks - reference_id: PMID:18209100 supporting_text: ESCRT-III polymers delineate and help generate the luminal vesicles of multivesicular bodies - reference_id: PMID:18209100 supporting_text: Multivesicular bodies (MVBs) are mid-stage endosomes that contain intraluminal vesicles - reference_id: UniProt:Q9BY43 supporting_text: Cytoplasmic vesicle membrane. Late endosome membrane - reference_id: UniProt:Q9BY43 supporting_text: Membrane-associated - term: id: GO:0046761 label: viral budding from plasma membrane evidence_type: IEA original_reference_id: GO_REF:0000117 qualifier: involved_in review: summary: 'True or plausible non-core CHMP4A ESCRT context: viral budding from plasma membrane.' action: KEEP_AS_NON_CORE reason: Viral budding is directly supported as ESCRT hijacking but is not an endogenous core CHMP4A proteostasis function. supported_by: - reference_id: PMID:18511562 supporting_text: ALIX protein must bind and recruit CHMP4 subunits of the ESCRT-III complex - reference_id: PMID:24878737 supporting_text: Structure of cellular ESCRT-III spirals and their relationship to HIV budding - reference_id: UniProt:Q9BY43 supporting_text: Probable core component of the endosomal sorting required for transport complex III (ESCRT-III) - reference_id: UniProt:Q9BY43 supporting_text: involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs - term: id: GO:0061952 label: midbody abscission evidence_type: IEA original_reference_id: GO_REF:0000117 qualifier: involved_in review: summary: 'True or plausible non-core CHMP4A ESCRT context: midbody abscission.' action: KEEP_AS_NON_CORE reason: Cytokinesis/midbody and spindle annotations are supported ESCRT output contexts, but they are not the central endolysosomal/proteostasis function emphasized for CHMP4A. supported_by: - reference_id: PMID:22724069 supporting_text: Borealin interacts directly with the Snf7 components of ESCRT-III - reference_id: PMID:22724069 supporting_text: controls abscission timing through inhibition of ESCRT-III Snf7 polymerization - reference_id: UniProt:Q9BY43 supporting_text: Probable core component of the endosomal sorting required for transport complex III (ESCRT-III) - reference_id: UniProt:Q9BY43 supporting_text: involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs - term: id: GO:0071985 label: multivesicular body sorting pathway evidence_type: IEA original_reference_id: GO_REF:0000117 qualifier: involved_in review: summary: 'Supported core CHMP4A ESCRT-III/MVB membrane-remodeling annotation: multivesicular body sorting pathway.' action: ACCEPT reason: CHMP4A is a core ESCRT-III/Snf7-family subunit that polymerizes on endosomal and MVB membranes to promote membrane budding/fission and MVB cargo sorting. supported_by: - reference_id: UniProt:Q9BY43 supporting_text: Probable core component of the endosomal sorting required for transport complex III (ESCRT-III) - reference_id: UniProt:Q9BY43 supporting_text: involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs - reference_id: UniProt:Q9BY43 supporting_text: believed to mediate the necessary vesicle extrusion and/or membrane fission activities - reference_id: PMID:18209100 supporting_text: form novel membrane-attached filaments that can promote or stabilize negative curvature and outward budding - reference_id: PMID:19234443 supporting_text: ESCRT-III has the instrinsic ability to drive the scission of membrane necks - reference_id: PMID:18209100 supporting_text: ESCRT-III polymers delineate and help generate the luminal vesicles of multivesicular bodies - reference_id: PMID:18209100 supporting_text: Multivesicular bodies (MVBs) are mid-stage endosomes that contain intraluminal vesicles - reference_id: UniProt:Q9BY43 supporting_text: Cytoplasmic vesicle membrane. Late endosome membrane - reference_id: UniProt:Q9BY43 supporting_text: Membrane-associated - term: id: GO:0097352 label: autophagosome maturation evidence_type: IEA original_reference_id: GO_REF:0000117 qualifier: involved_in review: summary: 'Supported PN-relevant autophagy/endolysosomal CHMP4A context: autophagosome maturation.' action: ACCEPT reason: CHMP4A/Snf7-1 depletion causes autophagosome accumulation in human neurons, and ESCRT/MVB function is required for autophagic degradation; this supports retaining autophagy and autophagosome-context annotations without claiming CHMP4A alone was directly assayed as the phagophore-sealing effector. supported_by: - reference_id: PMID:21975012 supporting_text: SiRNA knockdown of hSnf7-1 in human neurons leads to autophagosome accumulation - reference_id: PMID:17984323 supporting_text: Functional multivesicular bodies are required for autophagic clearance - reference_id: UniProt:Q9BY43 supporting_text: Probable core component of the endosomal sorting required for transport complex III (ESCRT-III) - reference_id: UniProt:Q9BY43 supporting_text: involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs - term: id: GO:1901673 label: regulation of mitotic spindle assembly evidence_type: IEA original_reference_id: GO_REF:0000117 qualifier: involved_in review: summary: 'True or plausible non-core CHMP4A ESCRT context: regulation of mitotic spindle assembly.' action: KEEP_AS_NON_CORE reason: Cytokinesis/midbody and spindle annotations are supported ESCRT output contexts, but they are not the central endolysosomal/proteostasis function emphasized for CHMP4A. supported_by: - reference_id: PMID:22724069 supporting_text: Borealin interacts directly with the Snf7 components of ESCRT-III - reference_id: PMID:22724069 supporting_text: controls abscission timing through inhibition of ESCRT-III Snf7 polymerization - reference_id: UniProt:Q9BY43 supporting_text: Probable core component of the endosomal sorting required for transport complex III (ESCRT-III) - reference_id: UniProt:Q9BY43 supporting_text: involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs - term: id: GO:1902774 label: late endosome to lysosome transport evidence_type: IEA original_reference_id: GO_REF:0000117 qualifier: involved_in review: summary: 'Supported PN-relevant autophagy/endolysosomal CHMP4A context: late endosome to lysosome transport.' action: ACCEPT reason: CHMP4A/Snf7-1 depletion causes autophagosome accumulation in human neurons, and ESCRT/MVB function is required for autophagic degradation; this supports retaining autophagy and autophagosome-context annotations without claiming CHMP4A alone was directly assayed as the phagophore-sealing effector. supported_by: - reference_id: PMID:21975012 supporting_text: SiRNA knockdown of hSnf7-1 in human neurons leads to autophagosome accumulation - reference_id: PMID:17984323 supporting_text: Functional multivesicular bodies are required for autophagic clearance - reference_id: UniProt:Q9BY43 supporting_text: Probable core component of the endosomal sorting required for transport complex III (ESCRT-III) - reference_id: UniProt:Q9BY43 supporting_text: involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs - term: id: GO:1904930 label: amphisome membrane evidence_type: IEA original_reference_id: GO_REF:0000117 qualifier: located_in review: summary: 'Supported PN-relevant autophagy/endolysosomal CHMP4A context: amphisome membrane.' action: ACCEPT reason: CHMP4A/Snf7-1 depletion causes autophagosome accumulation in human neurons, and ESCRT/MVB function is required for autophagic degradation; this supports retaining autophagy and autophagosome-context annotations without claiming CHMP4A alone was directly assayed as the phagophore-sealing effector. supported_by: - reference_id: PMID:21975012 supporting_text: SiRNA knockdown of hSnf7-1 in human neurons leads to autophagosome accumulation - reference_id: PMID:17984323 supporting_text: Functional multivesicular bodies are required for autophagic clearance - reference_id: UniProt:Q9BY43 supporting_text: Probable core component of the endosomal sorting required for transport complex III (ESCRT-III) - reference_id: UniProt:Q9BY43 supporting_text: involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:16189514 qualifier: enables review: summary: 'Generic protein binding is not informative for CHMP4A: protein binding.' action: MARK_AS_OVER_ANNOTATED reason: CHMP4A has real ESCRT, ALIX, Borealin, VPS4, and high-throughput interactions, but the curated function should describe ESCRT-III polymerization, membrane bending/fission, and specific ESCRT-complex contexts rather than plain protein binding. supported_by: - reference_id: UniProt:Q9BY43 supporting_text: Probable core component of the endosomal sorting required for transport complex III (ESCRT-III) - reference_id: UniProt:Q9BY43 supporting_text: involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs - 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:18209100 supporting_text: assemble into regular approximately 5-nm filaments that curve and self-associate - reference_id: PMID:18209100 supporting_text: proteins hSnf7-1 (CHMP4A) and hSnf7-2 (CHMP4B) - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:16730941 qualifier: enables review: summary: 'Generic protein binding is not informative for CHMP4A: protein binding.' action: MARK_AS_OVER_ANNOTATED reason: CHMP4A has real ESCRT, ALIX, Borealin, VPS4, and high-throughput interactions, but the curated function should describe ESCRT-III polymerization, membrane bending/fission, and specific ESCRT-complex contexts rather than plain protein binding. supported_by: - reference_id: UniProt:Q9BY43 supporting_text: Probable core component of the endosomal sorting required for transport complex III (ESCRT-III) - reference_id: UniProt:Q9BY43 supporting_text: involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs - 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:18209100 supporting_text: assemble into regular approximately 5-nm filaments that curve and self-associate - reference_id: PMID:18209100 supporting_text: proteins hSnf7-1 (CHMP4A) and hSnf7-2 (CHMP4B) - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:17350572 qualifier: enables review: summary: 'Generic protein binding is not informative for CHMP4A: protein binding.' action: MARK_AS_OVER_ANNOTATED reason: CHMP4A has real ESCRT, ALIX, Borealin, VPS4, and high-throughput interactions, but the curated function should describe ESCRT-III polymerization, membrane bending/fission, and specific ESCRT-complex contexts rather than plain protein binding. supported_by: - reference_id: UniProt:Q9BY43 supporting_text: Probable core component of the endosomal sorting required for transport complex III (ESCRT-III) - reference_id: UniProt:Q9BY43 supporting_text: involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs - 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:18209100 supporting_text: assemble into regular approximately 5-nm filaments that curve and self-associate - reference_id: PMID:18209100 supporting_text: proteins hSnf7-1 (CHMP4A) and hSnf7-2 (CHMP4B) - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:18511562 qualifier: enables review: summary: 'Generic protein binding is not informative for CHMP4A: protein binding.' action: MARK_AS_OVER_ANNOTATED reason: CHMP4A has real ESCRT, ALIX, Borealin, VPS4, and high-throughput interactions, but the curated function should describe ESCRT-III polymerization, membrane bending/fission, and specific ESCRT-complex contexts rather than plain protein binding. supported_by: - reference_id: UniProt:Q9BY43 supporting_text: Probable core component of the endosomal sorting required for transport complex III (ESCRT-III) - reference_id: UniProt:Q9BY43 supporting_text: involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs - 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:18209100 supporting_text: assemble into regular approximately 5-nm filaments that curve and self-associate - reference_id: PMID:18209100 supporting_text: proteins hSnf7-1 (CHMP4A) and hSnf7-2 (CHMP4B) - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:25416956 qualifier: enables review: summary: 'Generic protein binding is not informative for CHMP4A: protein binding.' action: MARK_AS_OVER_ANNOTATED reason: CHMP4A has real ESCRT, ALIX, Borealin, VPS4, and high-throughput interactions, but the curated function should describe ESCRT-III polymerization, membrane bending/fission, and specific ESCRT-complex contexts rather than plain protein binding. supported_by: - reference_id: UniProt:Q9BY43 supporting_text: Probable core component of the endosomal sorting required for transport complex III (ESCRT-III) - reference_id: UniProt:Q9BY43 supporting_text: involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs - 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:18209100 supporting_text: assemble into regular approximately 5-nm filaments that curve and self-associate - reference_id: PMID:18209100 supporting_text: proteins hSnf7-1 (CHMP4A) and hSnf7-2 (CHMP4B) - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:31515488 qualifier: enables review: summary: 'Generic protein binding is not informative for CHMP4A: protein binding.' action: MARK_AS_OVER_ANNOTATED reason: CHMP4A has real ESCRT, ALIX, Borealin, VPS4, and high-throughput interactions, but the curated function should describe ESCRT-III polymerization, membrane bending/fission, and specific ESCRT-complex contexts rather than plain protein binding. supported_by: - reference_id: UniProt:Q9BY43 supporting_text: Probable core component of the endosomal sorting required for transport complex III (ESCRT-III) - reference_id: UniProt:Q9BY43 supporting_text: involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs - 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:18209100 supporting_text: assemble into regular approximately 5-nm filaments that curve and self-associate - reference_id: PMID:18209100 supporting_text: proteins hSnf7-1 (CHMP4A) and hSnf7-2 (CHMP4B) - term: id: GO:0000421 label: autophagosome membrane evidence_type: IDA original_reference_id: PMID:17984323 qualifier: located_in review: summary: 'Supported PN-relevant autophagy/endolysosomal CHMP4A context: autophagosome membrane.' action: ACCEPT reason: CHMP4A/Snf7-1 depletion causes autophagosome accumulation in human neurons, and ESCRT/MVB function is required for autophagic degradation; this supports retaining autophagy and autophagosome-context annotations without claiming CHMP4A alone was directly assayed as the phagophore-sealing effector. supported_by: - reference_id: PMID:21975012 supporting_text: SiRNA knockdown of hSnf7-1 in human neurons leads to autophagosome accumulation - reference_id: PMID:17984323 supporting_text: Functional multivesicular bodies are required for autophagic clearance - reference_id: UniProt:Q9BY43 supporting_text: Probable core component of the endosomal sorting required for transport complex III (ESCRT-III) - reference_id: UniProt:Q9BY43 supporting_text: involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs - term: id: GO:0000776 label: kinetochore evidence_type: IDA original_reference_id: PMID:26040712 qualifier: located_in review: summary: 'True or plausible non-core CHMP4A ESCRT context: kinetochore.' action: KEEP_AS_NON_CORE reason: Cytokinesis/midbody and spindle annotations are supported ESCRT output contexts, but they are not the central endolysosomal/proteostasis function emphasized for CHMP4A. supported_by: - reference_id: PMID:22724069 supporting_text: Borealin interacts directly with the Snf7 components of ESCRT-III - reference_id: PMID:22724069 supporting_text: controls abscission timing through inhibition of ESCRT-III Snf7 polymerization - reference_id: UniProt:Q9BY43 supporting_text: Probable core component of the endosomal sorting required for transport complex III (ESCRT-III) - reference_id: UniProt:Q9BY43 supporting_text: involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs - term: id: GO:0000815 label: ESCRT III complex evidence_type: NAS original_reference_id: PMID:36107470 qualifier: part_of review: summary: 'Supported core CHMP4A ESCRT-III/MVB membrane-remodeling annotation: ESCRT III complex.' action: ACCEPT reason: CHMP4A is a core ESCRT-III/Snf7-family subunit that polymerizes on endosomal and MVB membranes to promote membrane budding/fission and MVB cargo sorting. supported_by: - reference_id: UniProt:Q9BY43 supporting_text: Probable core component of the endosomal sorting required for transport complex III (ESCRT-III) - reference_id: UniProt:Q9BY43 supporting_text: involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs - reference_id: UniProt:Q9BY43 supporting_text: believed to mediate the necessary vesicle extrusion and/or membrane fission activities - reference_id: PMID:18209100 supporting_text: form novel membrane-attached filaments that can promote or stabilize negative curvature and outward budding - reference_id: PMID:19234443 supporting_text: ESCRT-III has the instrinsic ability to drive the scission of membrane necks - reference_id: PMID:18209100 supporting_text: ESCRT-III polymers delineate and help generate the luminal vesicles of multivesicular bodies - reference_id: PMID:18209100 supporting_text: Multivesicular bodies (MVBs) are mid-stage endosomes that contain intraluminal vesicles - reference_id: UniProt:Q9BY43 supporting_text: Cytoplasmic vesicle membrane. Late endosome membrane - reference_id: UniProt:Q9BY43 supporting_text: Membrane-associated - term: id: GO:0001778 label: plasma membrane repair evidence_type: IDA original_reference_id: PMID:24482116 qualifier: involved_in review: summary: 'True or plausible non-core CHMP4A ESCRT context: plasma membrane repair.' action: KEEP_AS_NON_CORE reason: Plasma membrane repair is a valid ESCRT output context, but the core CHMP4A function remains ESCRT-III membrane remodeling in endosomal/MVB and related compartments. 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 - reference_id: UniProt:Q9BY43 supporting_text: Probable core component of the endosomal sorting required for transport complex III (ESCRT-III) - reference_id: UniProt:Q9BY43 supporting_text: involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs - term: id: GO:0005643 label: nuclear pore evidence_type: IDA original_reference_id: PMID:26040713 qualifier: part_of review: summary: 'True or plausible non-core CHMP4A ESCRT context: nuclear pore.' action: KEEP_AS_NON_CORE reason: Nuclear envelope or nuclear pore repair/reassembly is a supported ESCRT-III context but is secondary to CHMP4A core ESCRT-III membrane-remodeling function. supported_by: - reference_id: PMID:26040713 supporting_text: ESCRT-III controls nuclear envelope reformation - reference_id: UniProt:Q9BY43 supporting_text: Probable core component of the endosomal sorting required for transport complex III (ESCRT-III) - reference_id: UniProt:Q9BY43 supporting_text: involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs - term: id: GO:0005765 label: lysosomal membrane evidence_type: IDA original_reference_id: PMID:17984323 qualifier: located_in review: summary: 'Supported PN-relevant autophagy/endolysosomal CHMP4A context: lysosomal membrane.' action: ACCEPT reason: CHMP4A/Snf7-1 depletion causes autophagosome accumulation in human neurons, and ESCRT/MVB function is required for autophagic degradation; this supports retaining autophagy and autophagosome-context annotations without claiming CHMP4A alone was directly assayed as the phagophore-sealing effector. supported_by: - reference_id: PMID:21975012 supporting_text: SiRNA knockdown of hSnf7-1 in human neurons leads to autophagosome accumulation - reference_id: PMID:17984323 supporting_text: Functional multivesicular bodies are required for autophagic clearance - reference_id: UniProt:Q9BY43 supporting_text: Probable core component of the endosomal sorting required for transport complex III (ESCRT-III) - reference_id: UniProt:Q9BY43 supporting_text: involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs - term: id: GO:0005828 label: kinetochore microtubule evidence_type: IDA original_reference_id: PMID:26040712 qualifier: located_in review: summary: 'True or plausible non-core CHMP4A ESCRT context: kinetochore microtubule.' action: KEEP_AS_NON_CORE reason: Cytokinesis/midbody and spindle annotations are supported ESCRT output contexts, but they are not the central endolysosomal/proteostasis function emphasized for CHMP4A. supported_by: - reference_id: PMID:22724069 supporting_text: Borealin interacts directly with the Snf7 components of ESCRT-III - reference_id: PMID:22724069 supporting_text: controls abscission timing through inhibition of ESCRT-III Snf7 polymerization - reference_id: UniProt:Q9BY43 supporting_text: Probable core component of the endosomal sorting required for transport complex III (ESCRT-III) - reference_id: UniProt:Q9BY43 supporting_text: involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs - term: id: GO:0005886 label: plasma membrane evidence_type: IDA original_reference_id: PMID:24878737 qualifier: located_in review: summary: 'True or plausible non-core CHMP4A ESCRT context: plasma membrane.' action: KEEP_AS_NON_CORE reason: This location or output context is supported or plausible for CHMP4A but is broad or secondary relative to its core ESCRT-III MVB/endosomal membrane-remodeling role. supported_by: - reference_id: UniProt:Q9BY43 supporting_text: believed to mediate the necessary vesicle extrusion and/or membrane fission activities - reference_id: PMID:18209100 supporting_text: form novel membrane-attached filaments that can promote or stabilize negative curvature and outward budding - reference_id: PMID:19234443 supporting_text: ESCRT-III has the instrinsic ability to drive the scission of membrane necks - reference_id: UniProt:Q9BY43 supporting_text: Cytoplasmic vesicle membrane. Late endosome membrane - reference_id: UniProt:Q9BY43 supporting_text: Membrane-associated - term: id: GO:0006914 label: autophagy evidence_type: IMP original_reference_id: PMID:17984323 qualifier: involved_in review: summary: 'Supported PN-relevant autophagy/endolysosomal CHMP4A context: autophagy.' action: ACCEPT reason: CHMP4A/Snf7-1 depletion causes autophagosome accumulation in human neurons, and ESCRT/MVB function is required for autophagic degradation; this supports retaining autophagy and autophagosome-context annotations without claiming CHMP4A alone was directly assayed as the phagophore-sealing effector. supported_by: - reference_id: PMID:21975012 supporting_text: SiRNA knockdown of hSnf7-1 in human neurons leads to autophagosome accumulation - reference_id: PMID:17984323 supporting_text: Functional multivesicular bodies are required for autophagic clearance - reference_id: UniProt:Q9BY43 supporting_text: Probable core component of the endosomal sorting required for transport complex III (ESCRT-III) - reference_id: UniProt:Q9BY43 supporting_text: involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs - term: id: GO:0006997 label: nucleus organization evidence_type: IMP original_reference_id: PMID:20616062 qualifier: involved_in review: summary: 'True or plausible non-core CHMP4A ESCRT context: nucleus organization.' action: KEEP_AS_NON_CORE reason: Nuclear envelope or nuclear pore repair/reassembly is a supported ESCRT-III context but is secondary to CHMP4A core ESCRT-III membrane-remodeling function. supported_by: - reference_id: PMID:26040713 supporting_text: ESCRT-III controls nuclear envelope reformation - reference_id: UniProt:Q9BY43 supporting_text: Probable core component of the endosomal sorting required for transport complex III (ESCRT-III) - reference_id: UniProt:Q9BY43 supporting_text: involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs - term: id: GO:0007080 label: mitotic metaphase chromosome alignment evidence_type: IMP original_reference_id: PMID:20616062 qualifier: involved_in review: summary: 'True or plausible non-core CHMP4A ESCRT context: mitotic metaphase chromosome alignment.' action: KEEP_AS_NON_CORE reason: Cytokinesis/midbody and spindle annotations are supported ESCRT output contexts, but they are not the central endolysosomal/proteostasis function emphasized for CHMP4A. supported_by: - reference_id: PMID:22724069 supporting_text: Borealin interacts directly with the Snf7 components of ESCRT-III - reference_id: PMID:22724069 supporting_text: controls abscission timing through inhibition of ESCRT-III Snf7 polymerization - reference_id: UniProt:Q9BY43 supporting_text: Probable core component of the endosomal sorting required for transport complex III (ESCRT-III) - reference_id: UniProt:Q9BY43 supporting_text: involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs - term: id: GO:0030496 label: midbody evidence_type: IDA original_reference_id: PMID:26040712 qualifier: located_in review: summary: 'True or plausible non-core CHMP4A ESCRT context: midbody.' action: KEEP_AS_NON_CORE reason: Cytokinesis/midbody and spindle annotations are supported ESCRT output contexts, but they are not the central endolysosomal/proteostasis function emphasized for CHMP4A. supported_by: - reference_id: PMID:22724069 supporting_text: Borealin interacts directly with the Snf7 components of ESCRT-III - reference_id: PMID:22724069 supporting_text: controls abscission timing through inhibition of ESCRT-III Snf7 polymerization - reference_id: UniProt:Q9BY43 supporting_text: Probable core component of the endosomal sorting required for transport complex III (ESCRT-III) - reference_id: UniProt:Q9BY43 supporting_text: involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs - term: id: GO:0031468 label: nuclear membrane reassembly evidence_type: IMP original_reference_id: PMID:26040713 qualifier: involved_in review: summary: 'True or plausible non-core CHMP4A ESCRT context: nuclear membrane reassembly.' action: KEEP_AS_NON_CORE reason: Nuclear envelope or nuclear pore repair/reassembly is a supported ESCRT-III context but is secondary to CHMP4A core ESCRT-III membrane-remodeling function. supported_by: - reference_id: PMID:26040713 supporting_text: ESCRT-III controls nuclear envelope reformation - reference_id: UniProt:Q9BY43 supporting_text: Probable core component of the endosomal sorting required for transport complex III (ESCRT-III) - reference_id: UniProt:Q9BY43 supporting_text: involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs - term: id: GO:0032585 label: multivesicular body membrane evidence_type: IDA original_reference_id: PMID:16554368 qualifier: located_in review: summary: 'Supported core CHMP4A ESCRT-III/MVB membrane-remodeling annotation: multivesicular body membrane.' action: ACCEPT reason: CHMP4A is a core ESCRT-III/Snf7-family subunit that polymerizes on endosomal and MVB membranes to promote membrane budding/fission and MVB cargo sorting. supported_by: - reference_id: UniProt:Q9BY43 supporting_text: Cytoplasmic vesicle membrane. Late endosome membrane - reference_id: UniProt:Q9BY43 supporting_text: Membrane-associated - reference_id: PMID:18209100 supporting_text: ESCRT-III polymers delineate and help generate the luminal vesicles of multivesicular bodies - reference_id: PMID:18209100 supporting_text: Multivesicular bodies (MVBs) are mid-stage endosomes that contain intraluminal vesicles - term: id: GO:0036258 label: multivesicular body assembly evidence_type: NAS original_reference_id: PMID:16505166 qualifier: involved_in review: summary: 'Supported core CHMP4A ESCRT-III/MVB membrane-remodeling annotation: multivesicular body assembly.' action: ACCEPT reason: CHMP4A is a core ESCRT-III/Snf7-family subunit that polymerizes on endosomal and MVB membranes to promote membrane budding/fission and MVB cargo sorting. supported_by: - reference_id: UniProt:Q9BY43 supporting_text: Probable core component of the endosomal sorting required for transport complex III (ESCRT-III) - reference_id: UniProt:Q9BY43 supporting_text: involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs - reference_id: UniProt:Q9BY43 supporting_text: believed to mediate the necessary vesicle extrusion and/or membrane fission activities - reference_id: PMID:18209100 supporting_text: form novel membrane-attached filaments that can promote or stabilize negative curvature and outward budding - reference_id: PMID:19234443 supporting_text: ESCRT-III has the instrinsic ability to drive the scission of membrane necks - reference_id: PMID:18209100 supporting_text: ESCRT-III polymers delineate and help generate the luminal vesicles of multivesicular bodies - reference_id: PMID:18209100 supporting_text: Multivesicular bodies (MVBs) are mid-stage endosomes that contain intraluminal vesicles - reference_id: UniProt:Q9BY43 supporting_text: Cytoplasmic vesicle membrane. Late endosome membrane - reference_id: UniProt:Q9BY43 supporting_text: Membrane-associated - term: id: GO:0039702 label: viral budding via host ESCRT complex evidence_type: IDA original_reference_id: PMID:24878737 qualifier: involved_in review: summary: 'True or plausible non-core CHMP4A ESCRT context: viral budding via host ESCRT complex.' action: KEEP_AS_NON_CORE reason: Viral budding is directly supported as ESCRT hijacking but is not an endogenous core CHMP4A proteostasis function. supported_by: - reference_id: PMID:18511562 supporting_text: ALIX protein must bind and recruit CHMP4 subunits of the ESCRT-III complex - reference_id: PMID:24878737 supporting_text: Structure of cellular ESCRT-III spirals and their relationship to HIV budding - reference_id: UniProt:Q9BY43 supporting_text: Probable core component of the endosomal sorting required for transport complex III (ESCRT-III) - reference_id: UniProt:Q9BY43 supporting_text: involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs - 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: 'Supported core CHMP4A ESCRT-III/MVB membrane-remodeling annotation: ubiquitin-dependent protein catabolic process via the multivesicular body sorting pathway.' action: ACCEPT reason: CHMP4A is a core ESCRT-III/Snf7-family subunit that polymerizes on endosomal and MVB membranes to promote membrane budding/fission and MVB cargo sorting. supported_by: - reference_id: UniProt:Q9BY43 supporting_text: Probable core component of the endosomal sorting required for transport complex III (ESCRT-III) - reference_id: UniProt:Q9BY43 supporting_text: involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs - reference_id: UniProt:Q9BY43 supporting_text: believed to mediate the necessary vesicle extrusion and/or membrane fission activities - reference_id: PMID:18209100 supporting_text: form novel membrane-attached filaments that can promote or stabilize negative curvature and outward budding - reference_id: PMID:19234443 supporting_text: ESCRT-III has the instrinsic ability to drive the scission of membrane necks - reference_id: PMID:18209100 supporting_text: ESCRT-III polymers delineate and help generate the luminal vesicles of multivesicular bodies - reference_id: PMID:18209100 supporting_text: Multivesicular bodies (MVBs) are mid-stage endosomes that contain intraluminal vesicles - reference_id: UniProt:Q9BY43 supporting_text: Cytoplasmic vesicle membrane. Late endosome membrane - reference_id: UniProt:Q9BY43 supporting_text: Membrane-associated - term: id: GO:0046761 label: viral budding from plasma membrane evidence_type: IDA original_reference_id: PMID:24878737 qualifier: involved_in review: summary: 'True or plausible non-core CHMP4A ESCRT context: viral budding from plasma membrane.' action: KEEP_AS_NON_CORE reason: Viral budding is directly supported as ESCRT hijacking but is not an endogenous core CHMP4A proteostasis function. supported_by: - reference_id: PMID:18511562 supporting_text: ALIX protein must bind and recruit CHMP4 subunits of the ESCRT-III complex - reference_id: PMID:24878737 supporting_text: Structure of cellular ESCRT-III spirals and their relationship to HIV budding - reference_id: UniProt:Q9BY43 supporting_text: Probable core component of the endosomal sorting required for transport complex III (ESCRT-III) - reference_id: UniProt:Q9BY43 supporting_text: involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs - term: id: GO:0051469 label: vesicle fusion with vacuole evidence_type: NAS original_reference_id: PMID:16505166 qualifier: involved_in review: summary: vesicle fusion with vacuole overstates a direct vesicle-fusion role for CHMP4A. action: MODIFY reason: CHMP4A is an ESCRT-III membrane-remodeling subunit in MVB/endolysosomal trafficking; cached evidence supports late endosome/MVB to lysosome traffic more directly than CHMP4A as a fusion effector. supported_by: - reference_id: UniProt:Q9BY43 supporting_text: Probable core component of the endosomal sorting required for transport complex III (ESCRT-III) - reference_id: UniProt:Q9BY43 supporting_text: involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs - reference_id: UniProt:Q9BY43 supporting_text: believed to mediate the necessary vesicle extrusion and/or membrane fission activities - reference_id: PMID:18209100 supporting_text: form novel membrane-attached filaments that can promote or stabilize negative curvature and outward budding - reference_id: PMID:19234443 supporting_text: ESCRT-III has the instrinsic ability to drive the scission of membrane necks 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: multivesicular body-lysosome fusion overstates a direct vesicle-fusion role for CHMP4A. action: MODIFY reason: CHMP4A is an ESCRT-III membrane-remodeling subunit in MVB/endolysosomal trafficking; cached evidence supports late endosome/MVB to lysosome traffic more directly than CHMP4A as a fusion effector. supported_by: - reference_id: UniProt:Q9BY43 supporting_text: Probable core component of the endosomal sorting required for transport complex III (ESCRT-III) - reference_id: UniProt:Q9BY43 supporting_text: involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs - reference_id: UniProt:Q9BY43 supporting_text: believed to mediate the necessary vesicle extrusion and/or membrane fission activities - reference_id: PMID:18209100 supporting_text: form novel membrane-attached filaments that can promote or stabilize negative curvature and outward budding - reference_id: PMID:19234443 supporting_text: ESCRT-III has the instrinsic ability to drive the scission of membrane necks 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: 'True or plausible non-core CHMP4A ESCRT context: midbody abscission.' action: KEEP_AS_NON_CORE reason: Cytokinesis/midbody and spindle annotations are supported ESCRT output contexts, but they are not the central endolysosomal/proteostasis function emphasized for CHMP4A. supported_by: - reference_id: PMID:22724069 supporting_text: Borealin interacts directly with the Snf7 components of ESCRT-III - reference_id: PMID:22724069 supporting_text: controls abscission timing through inhibition of ESCRT-III Snf7 polymerization - reference_id: UniProt:Q9BY43 supporting_text: Probable core component of the endosomal sorting required for transport complex III (ESCRT-III) - reference_id: UniProt:Q9BY43 supporting_text: involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs - term: id: GO:0071985 label: multivesicular body sorting pathway evidence_type: IDA original_reference_id: PMID:16554368 qualifier: involved_in review: summary: 'Supported core CHMP4A ESCRT-III/MVB membrane-remodeling annotation: multivesicular body sorting pathway.' action: ACCEPT reason: CHMP4A is a core ESCRT-III/Snf7-family subunit that polymerizes on endosomal and MVB membranes to promote membrane budding/fission and MVB cargo sorting. supported_by: - reference_id: UniProt:Q9BY43 supporting_text: Probable core component of the endosomal sorting required for transport complex III (ESCRT-III) - reference_id: UniProt:Q9BY43 supporting_text: involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs - reference_id: UniProt:Q9BY43 supporting_text: believed to mediate the necessary vesicle extrusion and/or membrane fission activities - reference_id: PMID:18209100 supporting_text: form novel membrane-attached filaments that can promote or stabilize negative curvature and outward budding - reference_id: PMID:19234443 supporting_text: ESCRT-III has the instrinsic ability to drive the scission of membrane necks - reference_id: PMID:18209100 supporting_text: ESCRT-III polymers delineate and help generate the luminal vesicles of multivesicular bodies - reference_id: PMID:18209100 supporting_text: Multivesicular bodies (MVBs) are mid-stage endosomes that contain intraluminal vesicles - reference_id: UniProt:Q9BY43 supporting_text: Cytoplasmic vesicle membrane. Late endosome membrane - reference_id: UniProt:Q9BY43 supporting_text: Membrane-associated - term: id: GO:0090148 label: membrane fission evidence_type: NAS original_reference_id: PMID:19234443 qualifier: involved_in review: summary: 'Supported core CHMP4A ESCRT-III/MVB membrane-remodeling annotation: membrane fission.' action: ACCEPT reason: CHMP4A is a core ESCRT-III/Snf7-family subunit that polymerizes on endosomal and MVB membranes to promote membrane budding/fission and MVB cargo sorting. supported_by: - reference_id: UniProt:Q9BY43 supporting_text: believed to mediate the necessary vesicle extrusion and/or membrane fission activities - reference_id: PMID:18209100 supporting_text: form novel membrane-attached filaments that can promote or stabilize negative curvature and outward budding - reference_id: PMID:19234443 supporting_text: ESCRT-III has the instrinsic ability to drive the scission of membrane necks - reference_id: PMID:18209100 supporting_text: assemble into regular approximately 5-nm filaments that curve and self-associate - reference_id: PMID:18209100 supporting_text: proteins hSnf7-1 (CHMP4A) and hSnf7-2 (CHMP4B) - term: id: GO:0097352 label: autophagosome maturation evidence_type: IMP original_reference_id: PMID:17984323 qualifier: involved_in review: summary: 'Supported PN-relevant autophagy/endolysosomal CHMP4A context: autophagosome maturation.' action: ACCEPT reason: CHMP4A/Snf7-1 depletion causes autophagosome accumulation in human neurons, and ESCRT/MVB function is required for autophagic degradation; this supports retaining autophagy and autophagosome-context annotations without claiming CHMP4A alone was directly assayed as the phagophore-sealing effector. supported_by: - reference_id: PMID:21975012 supporting_text: SiRNA knockdown of hSnf7-1 in human neurons leads to autophagosome accumulation - reference_id: PMID:17984323 supporting_text: Functional multivesicular bodies are required for autophagic clearance - reference_id: UniProt:Q9BY43 supporting_text: Probable core component of the endosomal sorting required for transport complex III (ESCRT-III) - reference_id: UniProt:Q9BY43 supporting_text: involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs - term: id: GO:1901673 label: regulation of mitotic spindle assembly evidence_type: IMP original_reference_id: PMID:20616062 qualifier: involved_in review: summary: 'True or plausible non-core CHMP4A ESCRT context: regulation of mitotic spindle assembly.' action: KEEP_AS_NON_CORE reason: Cytokinesis/midbody and spindle annotations are supported ESCRT output contexts, but they are not the central endolysosomal/proteostasis function emphasized for CHMP4A. supported_by: - reference_id: PMID:22724069 supporting_text: Borealin interacts directly with the Snf7 components of ESCRT-III - reference_id: PMID:22724069 supporting_text: controls abscission timing through inhibition of ESCRT-III Snf7 polymerization - reference_id: UniProt:Q9BY43 supporting_text: Probable core component of the endosomal sorting required for transport complex III (ESCRT-III) - reference_id: UniProt:Q9BY43 supporting_text: involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs - term: id: GO:1902774 label: late endosome to lysosome transport evidence_type: IMP original_reference_id: PMID:17984323 qualifier: involved_in review: summary: 'Supported PN-relevant autophagy/endolysosomal CHMP4A context: late endosome to lysosome transport.' action: ACCEPT reason: CHMP4A/Snf7-1 depletion causes autophagosome accumulation in human neurons, and ESCRT/MVB function is required for autophagic degradation; this supports retaining autophagy and autophagosome-context annotations without claiming CHMP4A alone was directly assayed as the phagophore-sealing effector. supported_by: - reference_id: PMID:21975012 supporting_text: SiRNA knockdown of hSnf7-1 in human neurons leads to autophagosome accumulation - reference_id: PMID:17984323 supporting_text: Functional multivesicular bodies are required for autophagic clearance - reference_id: UniProt:Q9BY43 supporting_text: Probable core component of the endosomal sorting required for transport complex III (ESCRT-III) - reference_id: UniProt:Q9BY43 supporting_text: involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs - term: id: GO:1904930 label: amphisome membrane evidence_type: IDA original_reference_id: PMID:17984323 qualifier: located_in review: summary: 'Supported PN-relevant autophagy/endolysosomal CHMP4A context: amphisome membrane.' action: ACCEPT reason: CHMP4A/Snf7-1 depletion causes autophagosome accumulation in human neurons, and ESCRT/MVB function is required for autophagic degradation; this supports retaining autophagy and autophagosome-context annotations without claiming CHMP4A alone was directly assayed as the phagophore-sealing effector. supported_by: - reference_id: PMID:21975012 supporting_text: SiRNA knockdown of hSnf7-1 in human neurons leads to autophagosome accumulation - reference_id: PMID:17984323 supporting_text: Functional multivesicular bodies are required for autophagic clearance - reference_id: UniProt:Q9BY43 supporting_text: Probable core component of the endosomal sorting required for transport complex III (ESCRT-III) - reference_id: UniProt:Q9BY43 supporting_text: involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs - term: id: GO:0050877 label: nervous system process evidence_type: IMP original_reference_id: PMID:21975012 qualifier: involved_in review: summary: 'True or plausible non-core CHMP4A ESCRT context: nervous system process.' action: KEEP_AS_NON_CORE reason: The neuron paper supports CHMP4A-dependent neuronal survival and cargo turnover, but nervous system process is a broad phenotype rather than CHMP4A core molecular/cellular function. supported_by: - reference_id: PMID:21975012 supporting_text: hSnf7-1 and hSnf7-2 are required for the survival of human neurons - reference_id: PMID:21975012 supporting_text: hSnf7-1 and hSnf7-2 may have preferred interacting partners to form distinct ESCRT-III with different cellular functions - term: id: GO:0071985 label: multivesicular body sorting pathway evidence_type: IMP original_reference_id: PMID:21975012 qualifier: involved_in review: summary: 'Supported core CHMP4A ESCRT-III/MVB membrane-remodeling annotation: multivesicular body sorting pathway.' action: ACCEPT reason: CHMP4A is a core ESCRT-III/Snf7-family subunit that polymerizes on endosomal and MVB membranes to promote membrane budding/fission and MVB cargo sorting. supported_by: - reference_id: UniProt:Q9BY43 supporting_text: Probable core component of the endosomal sorting required for transport complex III (ESCRT-III) - reference_id: UniProt:Q9BY43 supporting_text: involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs - reference_id: UniProt:Q9BY43 supporting_text: believed to mediate the necessary vesicle extrusion and/or membrane fission activities - reference_id: PMID:18209100 supporting_text: form novel membrane-attached filaments that can promote or stabilize negative curvature and outward budding - reference_id: PMID:19234443 supporting_text: ESCRT-III has the instrinsic ability to drive the scission of membrane necks - reference_id: PMID:18209100 supporting_text: ESCRT-III polymers delineate and help generate the luminal vesicles of multivesicular bodies - reference_id: PMID:18209100 supporting_text: Multivesicular bodies (MVBs) are mid-stage endosomes that contain intraluminal vesicles - reference_id: UniProt:Q9BY43 supporting_text: Cytoplasmic vesicle membrane. Late endosome membrane - reference_id: UniProt:Q9BY43 supporting_text: Membrane-associated - term: id: GO:0000815 label: ESCRT III complex evidence_type: IDA original_reference_id: PMID:18209100 qualifier: part_of review: summary: 'Supported core CHMP4A ESCRT-III/MVB membrane-remodeling annotation: ESCRT III complex.' action: ACCEPT reason: CHMP4A is a core ESCRT-III/Snf7-family subunit that polymerizes on endosomal and MVB membranes to promote membrane budding/fission and MVB cargo sorting. supported_by: - reference_id: UniProt:Q9BY43 supporting_text: Probable core component of the endosomal sorting required for transport complex III (ESCRT-III) - reference_id: UniProt:Q9BY43 supporting_text: involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs - reference_id: UniProt:Q9BY43 supporting_text: believed to mediate the necessary vesicle extrusion and/or membrane fission activities - reference_id: PMID:18209100 supporting_text: form novel membrane-attached filaments that can promote or stabilize negative curvature and outward budding - reference_id: PMID:19234443 supporting_text: ESCRT-III has the instrinsic ability to drive the scission of membrane necks - reference_id: PMID:18209100 supporting_text: ESCRT-III polymers delineate and help generate the luminal vesicles of multivesicular bodies - reference_id: PMID:18209100 supporting_text: Multivesicular bodies (MVBs) are mid-stage endosomes that contain intraluminal vesicles - reference_id: UniProt:Q9BY43 supporting_text: Cytoplasmic vesicle membrane. Late endosome membrane - reference_id: UniProt:Q9BY43 supporting_text: Membrane-associated - term: id: GO:0042802 label: identical protein binding evidence_type: IPI original_reference_id: PMID:18209100 qualifier: enables review: summary: identical protein binding captures CHMP4A self-association but is less accurate than ESCRT-III polymerization and membrane bending. action: MODIFY reason: CHMP4A forms curved ESCRT-III filaments/polymers that bend membranes; homodimer or identical-protein binding terms are weaker molecular descriptions. supported_by: - reference_id: UniProt:Q9BY43 supporting_text: Probable core component of the endosomal sorting required for transport complex III (ESCRT-III) - reference_id: UniProt:Q9BY43 supporting_text: involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs - reference_id: UniProt:Q9BY43 supporting_text: believed to mediate the necessary vesicle extrusion and/or membrane fission activities - reference_id: PMID:18209100 supporting_text: form novel membrane-attached filaments that can promote or stabilize negative curvature and outward budding - reference_id: PMID:19234443 supporting_text: ESCRT-III has the instrinsic ability to drive the scission of membrane necks proposed_replacement_terms: - id: GO:0051258 label: protein polymerization - id: GO:0180020 label: membrane bending activity - term: id: GO:0051258 label: protein polymerization evidence_type: IMP original_reference_id: PMID:18209100 qualifier: involved_in review: summary: 'Supported core CHMP4A ESCRT-III/MVB membrane-remodeling annotation: protein polymerization.' action: ACCEPT reason: CHMP4A is a core ESCRT-III/Snf7-family subunit that polymerizes on endosomal and MVB membranes to promote membrane budding/fission and MVB cargo sorting. supported_by: - reference_id: PMID:18209100 supporting_text: assemble into regular approximately 5-nm filaments that curve and self-associate - reference_id: PMID:18209100 supporting_text: proteins hSnf7-1 (CHMP4A) and hSnf7-2 (CHMP4B) - reference_id: UniProt:Q9BY43 supporting_text: believed to mediate the necessary vesicle extrusion and/or membrane fission activities - reference_id: PMID:18209100 supporting_text: form novel membrane-attached filaments that can promote or stabilize negative curvature and outward budding - reference_id: PMID:19234443 supporting_text: ESCRT-III has the instrinsic ability to drive the scission of membrane necks - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:18641129 qualifier: enables review: summary: 'Generic protein binding is not informative for CHMP4A: protein binding.' action: MARK_AS_OVER_ANNOTATED reason: CHMP4A has real ESCRT, ALIX, Borealin, VPS4, and high-throughput interactions, but the curated function should describe ESCRT-III polymerization, membrane bending/fission, and specific ESCRT-complex contexts rather than plain protein binding. supported_by: - reference_id: UniProt:Q9BY43 supporting_text: Probable core component of the endosomal sorting required for transport complex III (ESCRT-III) - reference_id: UniProt:Q9BY43 supporting_text: involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs - 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:18209100 supporting_text: assemble into regular approximately 5-nm filaments that curve and self-associate - reference_id: PMID:18209100 supporting_text: proteins hSnf7-1 (CHMP4A) and hSnf7-2 (CHMP4B) - term: id: GO:0016236 label: macroautophagy evidence_type: TAS original_reference_id: PMID:20588296 qualifier: involved_in review: summary: 'Supported PN-relevant autophagy/endolysosomal CHMP4A context: macroautophagy.' action: ACCEPT reason: CHMP4A/Snf7-1 depletion causes autophagosome accumulation in human neurons, and ESCRT/MVB function is required for autophagic degradation; this supports retaining autophagy and autophagosome-context annotations without claiming CHMP4A alone was directly assayed as the phagophore-sealing effector. supported_by: - reference_id: PMID:21975012 supporting_text: SiRNA knockdown of hSnf7-1 in human neurons leads to autophagosome accumulation - reference_id: PMID:17984323 supporting_text: Functional multivesicular bodies are required for autophagic clearance - reference_id: UniProt:Q9BY43 supporting_text: Probable core component of the endosomal sorting required for transport complex III (ESCRT-III) - reference_id: UniProt:Q9BY43 supporting_text: involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs - term: id: GO:0000815 label: ESCRT III complex evidence_type: TAS original_reference_id: PMID:20588296 qualifier: part_of review: summary: 'Supported core CHMP4A ESCRT-III/MVB membrane-remodeling annotation: ESCRT III complex.' action: ACCEPT reason: CHMP4A is a core ESCRT-III/Snf7-family subunit that polymerizes on endosomal and MVB membranes to promote membrane budding/fission and MVB cargo sorting. supported_by: - reference_id: UniProt:Q9BY43 supporting_text: Probable core component of the endosomal sorting required for transport complex III (ESCRT-III) - reference_id: UniProt:Q9BY43 supporting_text: involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs - reference_id: UniProt:Q9BY43 supporting_text: believed to mediate the necessary vesicle extrusion and/or membrane fission activities - reference_id: PMID:18209100 supporting_text: form novel membrane-attached filaments that can promote or stabilize negative curvature and outward budding - reference_id: PMID:19234443 supporting_text: ESCRT-III has the instrinsic ability to drive the scission of membrane necks - reference_id: PMID:18209100 supporting_text: ESCRT-III polymers delineate and help generate the luminal vesicles of multivesicular bodies - reference_id: PMID:18209100 supporting_text: Multivesicular bodies (MVBs) are mid-stage endosomes that contain intraluminal vesicles - reference_id: UniProt:Q9BY43 supporting_text: Cytoplasmic vesicle membrane. Late endosome membrane - reference_id: UniProt:Q9BY43 supporting_text: Membrane-associated - term: id: GO:0036258 label: multivesicular body assembly evidence_type: TAS original_reference_id: PMID:20588296 qualifier: involved_in review: summary: 'Supported core CHMP4A ESCRT-III/MVB membrane-remodeling annotation: multivesicular body assembly.' action: ACCEPT reason: CHMP4A is a core ESCRT-III/Snf7-family subunit that polymerizes on endosomal and MVB membranes to promote membrane budding/fission and MVB cargo sorting. supported_by: - reference_id: UniProt:Q9BY43 supporting_text: Probable core component of the endosomal sorting required for transport complex III (ESCRT-III) - reference_id: UniProt:Q9BY43 supporting_text: involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs - reference_id: UniProt:Q9BY43 supporting_text: believed to mediate the necessary vesicle extrusion and/or membrane fission activities - reference_id: PMID:18209100 supporting_text: form novel membrane-attached filaments that can promote or stabilize negative curvature and outward budding - reference_id: PMID:19234443 supporting_text: ESCRT-III has the instrinsic ability to drive the scission of membrane necks - reference_id: PMID:18209100 supporting_text: ESCRT-III polymers delineate and help generate the luminal vesicles of multivesicular bodies - reference_id: PMID:18209100 supporting_text: Multivesicular bodies (MVBs) are mid-stage endosomes that contain intraluminal vesicles - reference_id: UniProt:Q9BY43 supporting_text: Cytoplasmic vesicle membrane. Late endosome membrane - reference_id: UniProt:Q9BY43 supporting_text: Membrane-associated - term: id: GO:0039702 label: viral budding via host ESCRT complex evidence_type: TAS original_reference_id: PMID:20588296 qualifier: involved_in review: summary: 'True or plausible non-core CHMP4A ESCRT context: viral budding via host ESCRT complex.' action: KEEP_AS_NON_CORE reason: Viral budding is directly supported as ESCRT hijacking but is not an endogenous core CHMP4A proteostasis function. supported_by: - reference_id: PMID:18511562 supporting_text: ALIX protein must bind and recruit CHMP4 subunits of the ESCRT-III complex - reference_id: PMID:24878737 supporting_text: Structure of cellular ESCRT-III spirals and their relationship to HIV budding - reference_id: UniProt:Q9BY43 supporting_text: Probable core component of the endosomal sorting required for transport complex III (ESCRT-III) - reference_id: UniProt:Q9BY43 supporting_text: involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs - term: id: GO:0000815 label: ESCRT III complex evidence_type: IDA original_reference_id: PMID:24878737 qualifier: part_of review: summary: 'Supported core CHMP4A ESCRT-III/MVB membrane-remodeling annotation: ESCRT III complex.' action: ACCEPT reason: CHMP4A is a core ESCRT-III/Snf7-family subunit that polymerizes on endosomal and MVB membranes to promote membrane budding/fission and MVB cargo sorting. supported_by: - reference_id: UniProt:Q9BY43 supporting_text: Probable core component of the endosomal sorting required for transport complex III (ESCRT-III) - reference_id: UniProt:Q9BY43 supporting_text: involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs - reference_id: UniProt:Q9BY43 supporting_text: believed to mediate the necessary vesicle extrusion and/or membrane fission activities - reference_id: PMID:18209100 supporting_text: form novel membrane-attached filaments that can promote or stabilize negative curvature and outward budding - reference_id: PMID:19234443 supporting_text: ESCRT-III has the instrinsic ability to drive the scission of membrane necks - reference_id: PMID:18209100 supporting_text: ESCRT-III polymers delineate and help generate the luminal vesicles of multivesicular bodies - reference_id: PMID:18209100 supporting_text: Multivesicular bodies (MVBs) are mid-stage endosomes that contain intraluminal vesicles - reference_id: UniProt:Q9BY43 supporting_text: Cytoplasmic vesicle membrane. Late endosome membrane - reference_id: UniProt:Q9BY43 supporting_text: Membrane-associated - term: id: GO:0005737 label: cytoplasm evidence_type: IDA original_reference_id: PMID:24878737 qualifier: located_in review: summary: 'True or plausible non-core CHMP4A ESCRT context: cytoplasm.' action: KEEP_AS_NON_CORE reason: This location or output context is supported or plausible for CHMP4A but is broad or secondary relative to its core ESCRT-III MVB/endosomal membrane-remodeling role. supported_by: - reference_id: PMID:21975012 supporting_text: Both hSnf7-1 and hSnf7-2 were expressed in human postmitotic neurons and seemed to be present in both the nucleus and cytoplasm - term: id: GO:0005768 label: endosome evidence_type: IDA original_reference_id: PMID:24878737 qualifier: colocalizes_with review: summary: 'Supported core CHMP4A ESCRT-III/MVB membrane-remodeling annotation: endosome.' action: ACCEPT reason: CHMP4A is a core ESCRT-III/Snf7-family subunit that polymerizes on endosomal and MVB membranes to promote membrane budding/fission and MVB cargo sorting. supported_by: - reference_id: UniProt:Q9BY43 supporting_text: Cytoplasmic vesicle membrane. Late endosome membrane - reference_id: UniProt:Q9BY43 supporting_text: Membrane-associated - reference_id: PMID:18209100 supporting_text: ESCRT-III polymers delineate and help generate the luminal vesicles of multivesicular bodies - reference_id: PMID:18209100 supporting_text: Multivesicular bodies (MVBs) are mid-stage endosomes that contain intraluminal vesicles - term: id: GO:0005886 label: plasma membrane evidence_type: IDA original_reference_id: PMID:24878737 qualifier: colocalizes_with review: summary: 'True or plausible non-core CHMP4A ESCRT context: plasma membrane.' action: KEEP_AS_NON_CORE reason: This location or output context is supported or plausible for CHMP4A but is broad or secondary relative to its core ESCRT-III MVB/endosomal membrane-remodeling role. supported_by: - reference_id: UniProt:Q9BY43 supporting_text: believed to mediate the necessary vesicle extrusion and/or membrane fission activities - reference_id: PMID:18209100 supporting_text: form novel membrane-attached filaments that can promote or stabilize negative curvature and outward budding - reference_id: PMID:19234443 supporting_text: ESCRT-III has the instrinsic ability to drive the scission of membrane necks - reference_id: UniProt:Q9BY43 supporting_text: Cytoplasmic vesicle membrane. Late endosome membrane - reference_id: UniProt:Q9BY43 supporting_text: Membrane-associated - term: id: GO:0010324 label: membrane invagination evidence_type: IMP original_reference_id: PMID:24878737 qualifier: involved_in review: summary: 'Supported core CHMP4A ESCRT-III/MVB membrane-remodeling annotation: membrane invagination.' action: ACCEPT reason: CHMP4A is a core ESCRT-III/Snf7-family subunit that polymerizes on endosomal and MVB membranes to promote membrane budding/fission and MVB cargo sorting. supported_by: - reference_id: UniProt:Q9BY43 supporting_text: believed to mediate the necessary vesicle extrusion and/or membrane fission activities - reference_id: PMID:18209100 supporting_text: form novel membrane-attached filaments that can promote or stabilize negative curvature and outward budding - reference_id: PMID:19234443 supporting_text: ESCRT-III has the instrinsic ability to drive the scission of membrane necks - reference_id: PMID:18209100 supporting_text: assemble into regular approximately 5-nm filaments that curve and self-associate - reference_id: PMID:18209100 supporting_text: proteins hSnf7-1 (CHMP4A) and hSnf7-2 (CHMP4B) - term: id: GO:0030117 label: membrane coat evidence_type: IMP original_reference_id: PMID:24878737 qualifier: part_of review: summary: 'Supported core CHMP4A ESCRT-III/MVB membrane-remodeling annotation: membrane coat.' action: ACCEPT reason: CHMP4A is a core ESCRT-III/Snf7-family subunit that polymerizes on endosomal and MVB membranes to promote membrane budding/fission and MVB cargo sorting. supported_by: - reference_id: UniProt:Q9BY43 supporting_text: believed to mediate the necessary vesicle extrusion and/or membrane fission activities - reference_id: PMID:18209100 supporting_text: form novel membrane-attached filaments that can promote or stabilize negative curvature and outward budding - reference_id: PMID:19234443 supporting_text: ESCRT-III has the instrinsic ability to drive the scission of membrane necks - reference_id: PMID:18209100 supporting_text: assemble into regular approximately 5-nm filaments that curve and self-associate - reference_id: PMID:18209100 supporting_text: proteins hSnf7-1 (CHMP4A) and hSnf7-2 (CHMP4B) - term: id: GO:0051258 label: protein polymerization evidence_type: IMP original_reference_id: PMID:24878737 qualifier: involved_in review: summary: 'Supported core CHMP4A ESCRT-III/MVB membrane-remodeling annotation: protein polymerization.' action: ACCEPT reason: CHMP4A is a core ESCRT-III/Snf7-family subunit that polymerizes on endosomal and MVB membranes to promote membrane budding/fission and MVB cargo sorting. supported_by: - reference_id: PMID:18209100 supporting_text: assemble into regular approximately 5-nm filaments that curve and self-associate - reference_id: PMID:18209100 supporting_text: proteins hSnf7-1 (CHMP4A) and hSnf7-2 (CHMP4B) - reference_id: UniProt:Q9BY43 supporting_text: believed to mediate the necessary vesicle extrusion and/or membrane fission activities - reference_id: PMID:18209100 supporting_text: form novel membrane-attached filaments that can promote or stabilize negative curvature and outward budding - reference_id: PMID:19234443 supporting_text: ESCRT-III has the instrinsic ability to drive the scission of membrane necks - term: id: GO:0039702 label: viral budding via host ESCRT complex evidence_type: IGI original_reference_id: PMID:24107264 qualifier: involved_in review: summary: 'True or plausible non-core CHMP4A ESCRT context: viral budding via host ESCRT complex.' action: KEEP_AS_NON_CORE reason: Viral budding is directly supported as ESCRT hijacking but is not an endogenous core CHMP4A proteostasis function. supported_by: - reference_id: PMID:18511562 supporting_text: ALIX protein must bind and recruit CHMP4 subunits of the ESCRT-III complex - reference_id: PMID:24878737 supporting_text: Structure of cellular ESCRT-III spirals and their relationship to HIV budding - reference_id: UniProt:Q9BY43 supporting_text: Probable core component of the endosomal sorting required for transport complex III (ESCRT-III) - reference_id: UniProt:Q9BY43 supporting_text: involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:14519844 qualifier: enables review: summary: 'Generic protein binding is not informative for CHMP4A: protein binding.' action: MARK_AS_OVER_ANNOTATED reason: CHMP4A has real ESCRT, ALIX, Borealin, VPS4, and high-throughput interactions, but the curated function should describe ESCRT-III polymerization, membrane bending/fission, and specific ESCRT-complex contexts rather than plain protein binding. supported_by: - reference_id: UniProt:Q9BY43 supporting_text: Probable core component of the endosomal sorting required for transport complex III (ESCRT-III) - reference_id: UniProt:Q9BY43 supporting_text: involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs - 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:18209100 supporting_text: assemble into regular approximately 5-nm filaments that curve and self-associate - reference_id: PMID:18209100 supporting_text: proteins hSnf7-1 (CHMP4A) and hSnf7-2 (CHMP4B) - term: id: GO:0042803 label: protein homodimerization activity evidence_type: IPI original_reference_id: PMID:14519844 qualifier: enables review: summary: protein homodimerization activity captures CHMP4A self-association but is less accurate than ESCRT-III polymerization and membrane bending. action: MODIFY reason: CHMP4A forms curved ESCRT-III filaments/polymers that bend membranes; homodimer or identical-protein binding terms are weaker molecular descriptions. supported_by: - reference_id: UniProt:Q9BY43 supporting_text: Probable core component of the endosomal sorting required for transport complex III (ESCRT-III) - reference_id: UniProt:Q9BY43 supporting_text: involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs - reference_id: UniProt:Q9BY43 supporting_text: believed to mediate the necessary vesicle extrusion and/or membrane fission activities - reference_id: PMID:18209100 supporting_text: form novel membrane-attached filaments that can promote or stabilize negative curvature and outward budding - reference_id: PMID:19234443 supporting_text: ESCRT-III has the instrinsic ability to drive the scission of membrane necks proposed_replacement_terms: - id: GO:0051258 label: protein polymerization - id: GO:0180020 label: membrane bending activity - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:14505570 qualifier: enables review: summary: 'Generic protein binding is not informative for CHMP4A: protein binding.' action: MARK_AS_OVER_ANNOTATED reason: CHMP4A has real ESCRT, ALIX, Borealin, VPS4, and high-throughput interactions, but the curated function should describe ESCRT-III polymerization, membrane bending/fission, and specific ESCRT-complex contexts rather than plain protein binding. supported_by: - reference_id: UniProt:Q9BY43 supporting_text: Probable core component of the endosomal sorting required for transport complex III (ESCRT-III) - reference_id: UniProt:Q9BY43 supporting_text: involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs - 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:18209100 supporting_text: assemble into regular approximately 5-nm filaments that curve and self-associate - reference_id: PMID:18209100 supporting_text: proteins hSnf7-1 (CHMP4A) and hSnf7-2 (CHMP4B) - term: id: GO:0000815 label: ESCRT III complex evidence_type: IDA original_reference_id: PMID:21975012 qualifier: part_of review: summary: 'Supported core CHMP4A ESCRT-III/MVB membrane-remodeling annotation: ESCRT III complex.' action: ACCEPT reason: CHMP4A is a core ESCRT-III/Snf7-family subunit that polymerizes on endosomal and MVB membranes to promote membrane budding/fission and MVB cargo sorting. supported_by: - reference_id: UniProt:Q9BY43 supporting_text: Probable core component of the endosomal sorting required for transport complex III (ESCRT-III) - reference_id: UniProt:Q9BY43 supporting_text: involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs - reference_id: UniProt:Q9BY43 supporting_text: believed to mediate the necessary vesicle extrusion and/or membrane fission activities - reference_id: PMID:18209100 supporting_text: form novel membrane-attached filaments that can promote or stabilize negative curvature and outward budding - reference_id: PMID:19234443 supporting_text: ESCRT-III has the instrinsic ability to drive the scission of membrane necks - reference_id: PMID:18209100 supporting_text: ESCRT-III polymers delineate and help generate the luminal vesicles of multivesicular bodies - reference_id: PMID:18209100 supporting_text: Multivesicular bodies (MVBs) are mid-stage endosomes that contain intraluminal vesicles - reference_id: UniProt:Q9BY43 supporting_text: Cytoplasmic vesicle membrane. Late endosome membrane - reference_id: UniProt:Q9BY43 supporting_text: Membrane-associated - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:21975012 qualifier: enables review: summary: 'Generic protein binding is not informative for CHMP4A: protein binding.' action: MARK_AS_OVER_ANNOTATED reason: CHMP4A has real ESCRT, ALIX, Borealin, VPS4, and high-throughput interactions, but the curated function should describe ESCRT-III polymerization, membrane bending/fission, and specific ESCRT-complex contexts rather than plain protein binding. supported_by: - reference_id: UniProt:Q9BY43 supporting_text: Probable core component of the endosomal sorting required for transport complex III (ESCRT-III) - reference_id: UniProt:Q9BY43 supporting_text: involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs - 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:18209100 supporting_text: assemble into regular approximately 5-nm filaments that curve and self-associate - reference_id: PMID:18209100 supporting_text: proteins hSnf7-1 (CHMP4A) and hSnf7-2 (CHMP4B) - term: id: GO:0005634 label: nucleus evidence_type: IDA original_reference_id: PMID:21975012 qualifier: located_in review: summary: 'True or plausible non-core CHMP4A ESCRT context: nucleus.' action: KEEP_AS_NON_CORE reason: This location or output context is supported or plausible for CHMP4A but is broad or secondary relative to its core ESCRT-III MVB/endosomal membrane-remodeling role. supported_by: - reference_id: PMID:21975012 supporting_text: Both hSnf7-1 and hSnf7-2 were expressed in human postmitotic neurons and seemed to be present in both the nucleus and cytoplasm - term: id: GO:0005737 label: cytoplasm evidence_type: IDA original_reference_id: PMID:21975012 qualifier: located_in review: summary: 'True or plausible non-core CHMP4A ESCRT context: cytoplasm.' action: KEEP_AS_NON_CORE reason: This location or output context is supported or plausible for CHMP4A but is broad or secondary relative to its core ESCRT-III MVB/endosomal membrane-remodeling role. supported_by: - reference_id: PMID:21975012 supporting_text: Both hSnf7-1 and hSnf7-2 were expressed in human postmitotic neurons and seemed to be present in both the nucleus and cytoplasm - term: id: GO:0006620 label: post-translational protein targeting to endoplasmic reticulum membrane evidence_type: IMP original_reference_id: PMID:21975012 qualifier: involved_in review: summary: The cited CHMP4A neuron paper does not support post-translational targeting to the ER membrane. action: REMOVE reason: PMID:21975012 supports CHMP4A/Snf7-1 in neuron survival, ESCRT-III cargo turnover, and autophagosome accumulation; it does not provide evidence that CHMP4A mediates ER membrane targeting. supported_by: - reference_id: PMID:21975012 supporting_text: hSnf7-1 and hSnf7-2 are required for the survival of human neurons - reference_id: PMID:21975012 supporting_text: hSnf7-1 and hSnf7-2 may have preferred interacting partners to form distinct ESCRT-III with different cellular functions - term: id: GO:0006900 label: vesicle budding from membrane evidence_type: IMP original_reference_id: PMID:18209100 qualifier: involved_in review: summary: 'Supported core CHMP4A ESCRT-III/MVB membrane-remodeling annotation: vesicle budding from membrane.' action: ACCEPT reason: CHMP4A is a core ESCRT-III/Snf7-family subunit that polymerizes on endosomal and MVB membranes to promote membrane budding/fission and MVB cargo sorting. supported_by: - reference_id: UniProt:Q9BY43 supporting_text: believed to mediate the necessary vesicle extrusion and/or membrane fission activities - reference_id: PMID:18209100 supporting_text: form novel membrane-attached filaments that can promote or stabilize negative curvature and outward budding - reference_id: PMID:19234443 supporting_text: ESCRT-III has the instrinsic ability to drive the scission of membrane necks - reference_id: PMID:18209100 supporting_text: assemble into regular approximately 5-nm filaments that curve and self-associate - reference_id: PMID:18209100 supporting_text: proteins hSnf7-1 (CHMP4A) and hSnf7-2 (CHMP4B) - term: id: GO:0006900 label: vesicle budding from membrane evidence_type: IGI original_reference_id: PMID:18209100 qualifier: involved_in review: summary: 'Supported core CHMP4A ESCRT-III/MVB membrane-remodeling annotation: vesicle budding from membrane.' action: ACCEPT reason: CHMP4A is a core ESCRT-III/Snf7-family subunit that polymerizes on endosomal and MVB membranes to promote membrane budding/fission and MVB cargo sorting. supported_by: - reference_id: UniProt:Q9BY43 supporting_text: believed to mediate the necessary vesicle extrusion and/or membrane fission activities - reference_id: PMID:18209100 supporting_text: form novel membrane-attached filaments that can promote or stabilize negative curvature and outward budding - reference_id: PMID:19234443 supporting_text: ESCRT-III has the instrinsic ability to drive the scission of membrane necks - reference_id: PMID:18209100 supporting_text: assemble into regular approximately 5-nm filaments that curve and self-associate - reference_id: PMID:18209100 supporting_text: proteins hSnf7-1 (CHMP4A) and hSnf7-2 (CHMP4B) - term: id: GO:0009898 label: cytoplasmic side of plasma membrane evidence_type: IDA original_reference_id: PMID:18209100 qualifier: located_in review: summary: 'True or plausible non-core CHMP4A ESCRT context: cytoplasmic side of plasma membrane.' action: KEEP_AS_NON_CORE reason: This location or output context is supported or plausible for CHMP4A but is broad or secondary relative to its core ESCRT-III MVB/endosomal membrane-remodeling role. supported_by: - reference_id: UniProt:Q9BY43 supporting_text: believed to mediate the necessary vesicle extrusion and/or membrane fission activities - reference_id: PMID:18209100 supporting_text: form novel membrane-attached filaments that can promote or stabilize negative curvature and outward budding - reference_id: PMID:19234443 supporting_text: ESCRT-III has the instrinsic ability to drive the scission of membrane necks - reference_id: UniProt:Q9BY43 supporting_text: Cytoplasmic vesicle membrane. Late endosome membrane - reference_id: UniProt:Q9BY43 supporting_text: Membrane-associated - term: id: GO:0051117 label: ATPase binding evidence_type: IPI original_reference_id: PMID:18209100 qualifier: enables review: summary: 'True or plausible non-core CHMP4A ESCRT context: ATPase binding.' action: KEEP_AS_NON_CORE reason: ATPase binding reflects VPS4 engagement with CHMP4A filaments and is useful context, but CHMP4A itself is the ESCRT-III polymerizing membrane-remodeling subunit. supported_by: - reference_id: PMID:18209100 supporting_text: Binding to a coexpressed adenosine triphosphate hydrolysis-deficient mutant of VPS4B draws these filaments together - reference_id: UniProt:Q9BY43 supporting_text: Interacts with VPS4A - term: id: GO:0097320 label: plasma membrane tubulation evidence_type: IMP original_reference_id: PMID:18209100 qualifier: involved_in review: summary: 'True or plausible non-core CHMP4A ESCRT context: plasma membrane tubulation.' action: KEEP_AS_NON_CORE reason: Plasma membrane tubulation is a useful overexpression/model phenotype for CHMP4A filament curvature, not the normal core biological process. supported_by: - reference_id: UniProt:Q9BY43 supporting_text: believed to mediate the necessary vesicle extrusion and/or membrane fission activities - reference_id: PMID:18209100 supporting_text: form novel membrane-attached filaments that can promote or stabilize negative curvature and outward budding - reference_id: PMID:19234443 supporting_text: ESCRT-III has the instrinsic ability to drive the scission of membrane necks - reference_id: UniProt:Q9BY43 supporting_text: Cytoplasmic vesicle membrane. Late endosome membrane - reference_id: UniProt:Q9BY43 supporting_text: Membrane-associated - term: id: GO:0097320 label: plasma membrane tubulation evidence_type: IGI original_reference_id: PMID:18209100 qualifier: involved_in review: summary: 'True or plausible non-core CHMP4A ESCRT context: plasma membrane tubulation.' action: KEEP_AS_NON_CORE reason: Plasma membrane tubulation is a useful overexpression/model phenotype for CHMP4A filament curvature, not the normal core biological process. supported_by: - reference_id: UniProt:Q9BY43 supporting_text: believed to mediate the necessary vesicle extrusion and/or membrane fission activities - reference_id: PMID:18209100 supporting_text: form novel membrane-attached filaments that can promote or stabilize negative curvature and outward budding - reference_id: PMID:19234443 supporting_text: ESCRT-III has the instrinsic ability to drive the scission of membrane necks - reference_id: UniProt:Q9BY43 supporting_text: Cytoplasmic vesicle membrane. Late endosome membrane - reference_id: UniProt:Q9BY43 supporting_text: Membrane-associated - term: id: GO:0005829 label: cytosol evidence_type: TAS original_reference_id: Reactome:R-HSA-3159232 qualifier: located_in review: summary: 'True or plausible non-core CHMP4A ESCRT context: cytosol.' action: KEEP_AS_NON_CORE reason: This location or output context is supported or plausible for CHMP4A but is broad or secondary relative to its core ESCRT-III MVB/endosomal membrane-remodeling role. supported_by: - reference_id: PMID:21975012 supporting_text: Both hSnf7-1 and hSnf7-2 were expressed in human postmitotic neurons and seemed to be present in both the nucleus and cytoplasm - term: id: GO:0005829 label: cytosol evidence_type: TAS original_reference_id: Reactome:R-HSA-917693 qualifier: located_in review: summary: 'True or plausible non-core CHMP4A ESCRT context: cytosol.' action: KEEP_AS_NON_CORE reason: This location or output context is supported or plausible for CHMP4A but is broad or secondary relative to its core ESCRT-III MVB/endosomal membrane-remodeling role. supported_by: - reference_id: PMID:21975012 supporting_text: Both hSnf7-1 and hSnf7-2 were expressed in human postmitotic neurons and seemed to be present in both the nucleus and cytoplasm - term: id: GO:0005829 label: cytosol evidence_type: TAS original_reference_id: Reactome:R-HSA-917700 qualifier: located_in review: summary: 'True or plausible non-core CHMP4A ESCRT context: cytosol.' action: KEEP_AS_NON_CORE reason: This location or output context is supported or plausible for CHMP4A but is broad or secondary relative to its core ESCRT-III MVB/endosomal membrane-remodeling role. supported_by: - reference_id: PMID:21975012 supporting_text: Both hSnf7-1 and hSnf7-2 were expressed in human postmitotic neurons and seemed to be present in both the nucleus and cytoplasm - term: id: GO:0005829 label: cytosol evidence_type: TAS original_reference_id: Reactome:R-HSA-9668389 qualifier: located_in review: summary: 'True or plausible non-core CHMP4A ESCRT context: cytosol.' action: KEEP_AS_NON_CORE reason: This location or output context is supported or plausible for CHMP4A but is broad or secondary relative to its core ESCRT-III MVB/endosomal membrane-remodeling role. supported_by: - reference_id: PMID:21975012 supporting_text: Both hSnf7-1 and hSnf7-2 were expressed in human postmitotic neurons and seemed to be present in both the nucleus and cytoplasm - term: id: GO:0005829 label: cytosol evidence_type: TAS original_reference_id: Reactome:R-HSA-9668395 qualifier: located_in review: summary: 'True or plausible non-core CHMP4A ESCRT context: cytosol.' action: KEEP_AS_NON_CORE reason: This location or output context is supported or plausible for CHMP4A but is broad or secondary relative to its core ESCRT-III MVB/endosomal membrane-remodeling role. supported_by: - reference_id: PMID:21975012 supporting_text: Both hSnf7-1 and hSnf7-2 were expressed in human postmitotic neurons and seemed to be present in both the nucleus and cytoplasm - term: id: GO:0005829 label: cytosol evidence_type: TAS original_reference_id: Reactome:R-HSA-9668398 qualifier: located_in review: summary: 'True or plausible non-core CHMP4A ESCRT context: cytosol.' action: KEEP_AS_NON_CORE reason: This location or output context is supported or plausible for CHMP4A but is broad or secondary relative to its core ESCRT-III MVB/endosomal membrane-remodeling role. supported_by: - reference_id: PMID:21975012 supporting_text: Both hSnf7-1 and hSnf7-2 were expressed in human postmitotic neurons and seemed to be present in both the nucleus and cytoplasm - term: id: GO:0005829 label: cytosol evidence_type: TAS original_reference_id: Reactome:R-HSA-9668405 qualifier: located_in review: summary: 'True or plausible non-core CHMP4A ESCRT context: cytosol.' action: KEEP_AS_NON_CORE reason: This location or output context is supported or plausible for CHMP4A but is broad or secondary relative to its core ESCRT-III MVB/endosomal membrane-remodeling role. supported_by: - reference_id: PMID:21975012 supporting_text: Both hSnf7-1 and hSnf7-2 were expressed in human postmitotic neurons and seemed to be present in both the nucleus and cytoplasm - term: id: GO:0005829 label: cytosol evidence_type: TAS original_reference_id: Reactome:R-HSA-9668415 qualifier: located_in review: summary: 'True or plausible non-core CHMP4A ESCRT context: cytosol.' action: KEEP_AS_NON_CORE reason: This location or output context is supported or plausible for CHMP4A but is broad or secondary relative to its core ESCRT-III MVB/endosomal membrane-remodeling role. supported_by: - reference_id: PMID:21975012 supporting_text: Both hSnf7-1 and hSnf7-2 were expressed in human postmitotic neurons and seemed to be present in both the nucleus and cytoplasm - term: id: GO:0005829 label: cytosol evidence_type: TAS original_reference_id: Reactome:R-HSA-9668419 qualifier: located_in review: summary: 'True or plausible non-core CHMP4A ESCRT context: cytosol.' action: KEEP_AS_NON_CORE reason: This location or output context is supported or plausible for CHMP4A but is broad or secondary relative to its core ESCRT-III MVB/endosomal membrane-remodeling role. supported_by: - reference_id: PMID:21975012 supporting_text: Both hSnf7-1 and hSnf7-2 were expressed in human postmitotic neurons and seemed to be present in both the nucleus and cytoplasm - term: id: GO:0030496 label: midbody evidence_type: IDA original_reference_id: PMID:22724069 qualifier: located_in review: summary: 'True or plausible non-core CHMP4A ESCRT context: midbody.' action: KEEP_AS_NON_CORE reason: Cytokinesis/midbody and spindle annotations are supported ESCRT output contexts, but they are not the central endolysosomal/proteostasis function emphasized for CHMP4A. supported_by: - reference_id: PMID:22724069 supporting_text: Borealin interacts directly with the Snf7 components of ESCRT-III - reference_id: PMID:22724069 supporting_text: controls abscission timing through inhibition of ESCRT-III Snf7 polymerization - reference_id: UniProt:Q9BY43 supporting_text: Probable core component of the endosomal sorting required for transport complex III (ESCRT-III) - reference_id: UniProt:Q9BY43 supporting_text: involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs - term: id: GO:0180020 label: membrane bending activity evidence_type: IDA original_reference_id: PMID:18209100 qualifier: enables review: summary: New CHMP4A molecular-function annotation supported by direct ESCRT-III filament/membrane curvature evidence. action: NEW reason: PMID:18209100 directly shows CHMP4A/hSnf7-1-containing ESCRT-III filaments promote or stabilize negative membrane curvature and outward budding, making membrane bending activity more informative than generic protein binding. supported_by: - reference_id: UniProt:Q9BY43 supporting_text: believed to mediate the necessary vesicle extrusion and/or membrane fission activities - reference_id: PMID:18209100 supporting_text: form novel membrane-attached filaments that can promote or stabilize negative curvature and outward budding - reference_id: PMID:19234443 supporting_text: ESCRT-III has the instrinsic ability to drive the scission of membrane necks - reference_id: PMID:18209100 supporting_text: assemble into regular approximately 5-nm filaments that curve and self-associate - reference_id: PMID:18209100 supporting_text: proteins hSnf7-1 (CHMP4A) and hSnf7-2 (CHMP4B) 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:16189514 title: Towards a proteome-scale map of the human protein-protein interaction network. 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:16730941 title: 'A systematic analysis of human CHMP protein interactions: additional MIT domain-containing proteins bind to multiple components of the human ESCRT III complex.' findings: [] - id: PMID:17350572 title: Structural and biochemical studies of ALIX/AIP1 and its role in retrovirus budding. findings: [] - id: PMID:17984323 title: Functional multivesicular bodies are required for autophagic clearance of protein aggregates associated with neurodegenerative disease. findings: [] - id: PMID:18209100 title: Plasma membrane deformation by circular arrays of ESCRT-III protein filaments. findings: [] - id: PMID:18511562 title: ALIX-CHMP4 interactions in the human ESCRT pathway. findings: [] - 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: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:21975012 title: ESCRT-III subunits Snf7-1 and Snf7-2 differentially regulate transmembrane cargos in hESC-derived human neurons. 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: [] - id: PMID:24107264 title: ESCRT requirements for EIAV budding. findings: [] - id: PMID:24482116 title: ESCRT machinery is required for plasma membrane repair. findings: [] - id: PMID:24878737 title: Structure of cellular ESCRT-III spirals and their relationship to HIV budding. findings: [] - id: PMID:25416956 title: A proteome-scale map of the human interactome network. 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:31515488 title: Extensive disruption of protein interactions by genetic variants across the allele frequency spectrum in human populations. findings: [] - id: PMID:36107470 title: Comprehensive analysis of the human ESCRT-III-MIT domain interactome reveals new cofactors for cytokinetic abscission. findings: [] - 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: UniProt:Q9BY43 title: UniProt entry for CHMP4A (Q9BY43) findings: - statement: CHMP4A is a probable core ESCRT-III component involved in MVB formation, endosomal cargo sorting, membrane fission, and exosomal release. - id: file:human/CHMP4A/CHMP4A-notes.md title: Local curation notes for CHMP4A findings: - statement: Local synthesis identifies ESCRT-III polymerization/membrane bending and MVB/endosomal sorting as core CHMP4A functions, with autophagy and other ESCRT outputs retained in context. core_functions: - molecular_function: id: GO:0180020 label: membrane bending activity description: CHMP4A/Snf7-1 is a core ESCRT-III structural subunit that polymerizes into curved membrane-associated filaments and promotes or stabilizes negative membrane curvature for reverse-topology budding/fission. in_complex: id: GO:0000815 label: ESCRT III complex directly_involved_in: - id: GO:0090148 label: membrane fission - id: GO:0006900 label: vesicle budding from membrane locations: - id: GO:0031902 label: late endosome membrane - id: GO:0032585 label: multivesicular body membrane supported_by: - reference_id: UniProt:Q9BY43 supporting_text: believed to mediate the necessary vesicle extrusion and/or membrane fission activities - reference_id: PMID:18209100 supporting_text: form novel membrane-attached filaments that can promote or stabilize negative curvature and outward budding - reference_id: PMID:19234443 supporting_text: ESCRT-III has the instrinsic ability to drive the scission of membrane necks - reference_id: PMID:18209100 supporting_text: assemble into regular approximately 5-nm filaments that curve and self-associate - reference_id: PMID:18209100 supporting_text: proteins hSnf7-1 (CHMP4A) and hSnf7-2 (CHMP4B) - description: CHMP4A-containing ESCRT-III assemblies mediate MVB intraluminal vesicle formation and ubiquitin-dependent endosomal cargo sorting toward endolysosomal degradation. in_complex: id: GO:0000815 label: ESCRT III complex directly_involved_in: - id: GO:0071985 label: multivesicular body sorting pathway - id: GO:0036258 label: multivesicular body assembly - id: GO:0043162 label: ubiquitin-dependent protein catabolic process via the multivesicular body sorting pathway locations: - id: GO:0032585 label: multivesicular body membrane - id: GO:0005768 label: endosome supported_by: - reference_id: UniProt:Q9BY43 supporting_text: Probable core component of the endosomal sorting required for transport complex III (ESCRT-III) - reference_id: UniProt:Q9BY43 supporting_text: involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs - reference_id: PMID:18209100 supporting_text: ESCRT-III polymers delineate and help generate the luminal vesicles of multivesicular bodies - reference_id: PMID:18209100 supporting_text: Multivesicular bodies (MVBs) are mid-stage endosomes that contain intraluminal vesicles - description: CHMP4A/Snf7-1 contributes to autophagy/autophagosome maturation contexts as part of ESCRT-dependent endolysosomal membrane remodeling; direct human-neuron knockdown causes autophagosome accumulation. in_complex: id: GO:0000815 label: ESCRT III complex directly_involved_in: - id: GO:0097352 label: autophagosome maturation - id: GO:0016236 label: macroautophagy locations: - id: GO:0000421 label: autophagosome membrane - id: GO:1904930 label: amphisome membrane - id: GO:0005765 label: lysosomal membrane supported_by: - reference_id: PMID:21975012 supporting_text: SiRNA knockdown of hSnf7-1 in human neurons leads to autophagosome accumulation - reference_id: PMID:17984323 supporting_text: Functional multivesicular bodies are required for autophagic clearance proposed_new_terms: [] suggested_questions: - question: Which CHMP4 paralog, CHMP4A, CHMP4B, or CHMP4C, is the dominant Snf7-family subunit during human phagophore closure and autophagosome maturation? - question: Should GO annotations distinguish direct CHMP4A membrane-bending/polymer function from broader ESCRT output processes such as viral budding, plasma membrane repair, and nuclear envelope sealing? - question: Does CHMP4A preferentially pair with CHMP2A in autophagy and endosomal cargo sorting, as suggested by human-neuron cargo turnover assays? suggested_experiments: - description: Use endogenous CHMP4A tagging and acute CHMP4A depletion/rescue during starvation-induced autophagy to image recruitment to phagophores, autophagosomes, and amphisomes. hypothesis: If CHMP4A directly participates in autophagosome maturation or closure, it should be transiently recruited to autophagy membranes and rescue should require its polymerization/membrane-binding region. - description: Compare wild-type CHMP4A with ALIX-binding and C-terminal autoinhibition mutants in MVB cargo sorting, ESCRT spiral formation, plasma membrane repair, and viral budding assays. hypothesis: CHMP4A polymerization and partner recruitment requirements differ across endogenous ESCRT outputs and virus-hijacked budding. - description: Biochemically reconstitute CHMP4A-containing human ESCRT-III polymers with CHMP2A/CHMP3/VPS4 and test membrane bending/scission on defined liposomes. hypothesis: CHMP4A contributes Snf7-family filament curvature that can drive membrane bending and support reverse-topology scission in a minimal human ESCRT-III module.