CHMP4C

Existing Annotations Review

GO Term	Evidence	Action	Reason
GO:0005635 nuclear envelope	IBA GO_REF:0000033	KEEP AS NON CORE	Summary: Plausible non-core CHMP4C nuclear-envelope ESCRT context: nuclear envelope. Reason: Nuclear envelope sealing/reassembly is a supported ESCRT-III context, but it is secondary to the CHMP4C-specific abscission-checkpoint role. Supporting Evidence: PMID:26040712 ESCRT-III, VPS4 and spastin cooperate to coordinate nuclear envelope sealing and spindle disassembly PMID:26040713 ESCRT-III controls nuclear envelope reformation
GO:0031468 nuclear membrane reassembly	IBA GO_REF:0000033	KEEP AS NON CORE	Summary: Plausible non-core CHMP4C nuclear-envelope ESCRT context: nuclear membrane reassembly. Reason: Nuclear envelope sealing/reassembly is a supported ESCRT-III context, but it is secondary to the CHMP4C-specific abscission-checkpoint role. Supporting Evidence: PMID:26040712 ESCRT-III, VPS4 and spastin cooperate to coordinate nuclear envelope sealing and spindle disassembly PMID:26040713 ESCRT-III controls nuclear envelope reformation
GO:0000815 ESCRT III complex	IBA GO_REF:0000033	ACCEPT	Summary: Supported CHMP4C ESCRT-III complex membership annotation: ESCRT III complex. Reason: CHMP4C is a Snf7-family CHMP4 subunit of ESCRT-III; its most specific cellular function is checkpoint regulation, but complex membership is sound. Supporting Evidence: UniProt:Q96CF2 Probable core component of the endosomal sorting required for transport complex III (ESCRT-III) UniProt:Q96CF2 ESCRT-III proteins mostly dissociate from the invaginating membrane before the ILV is released PMID:18511562 Bro1 domain of ALIX binds specifically to C-terminal residues of the human CHMP4 proteins (CHMP4A-C) PMID:36107470 CHMP4C performs a unique role in abscission checkpoint regulation file:human/CHMP4C/CHMP4C-notes.md CHMP4C still has bona fide ESCRT-III context.
GO:0009898 cytoplasmic side of plasma membrane	IBA GO_REF:0000033	KEEP AS NON CORE	Summary: True or plausible broad CHMP4C location: cytoplasmic side of plasma membrane. Reason: This location is compatible with CHMP4C cycling between cytosol and recruited ESCRT-III assemblies, but it is too broad to represent the core function by itself. Supporting Evidence: UniProt:Q96CF2 Cytoplasm. Cytosol UniProt:Q96CF2 Localizes to the midbody during late cytokinesis
GO:0032511 late endosome to vacuole transport via multivesicular body sorting pathway	IBA GO_REF:0000033	KEEP AS NON CORE	Summary: Plausible but non-core CHMP4C ESCRT/MVB context: late endosome to vacuole transport via multivesicular body sorting pathway. Reason: CHMP4C belongs to the CHMP4/ESCRT-III family, but CHMP4C-specific evidence points most strongly to abscission-checkpoint regulation; MVB/endosomal sorting annotations are retained as non-core ESCRT-family context. Supporting Evidence: UniProt:Q96CF2 involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs PMID:18511562 The ESCRT pathway facilitates membrane fission events during enveloped virus budding, multivesicular body formation, and cytokinesis PMID:22422861 depletion of CHMP4B prevented MHC-I degradation, whereas depletion of CHMP4A or CHMP4C had little effect file:human/CHMP4C/CHMP4C-notes.md broad MVB cargo-degradation annotations for CHMP4C should be retained, at most, as non-core/over-annotated ESCRT-family context
GO:0000776 kinetochore	IEA GO_REF:0000117	KEEP AS NON CORE	Summary: Plausible non-core CHMP4C centrosome/spindle/cell-cycle context: kinetochore. Reason: ESCRT-III/VPS4 perturbation affects centrosome and spindle maintenance, but these broad cell-cycle annotations are secondary to CHMP4C abscission-checkpoint regulation. Supporting Evidence: PMID:20616062 depletion of individual ESCRT-III and VPS4 proteins also altered centrosome and spindle pole numbers PMID:20616062 ESCRT-III/VPS4 proteins function at centrosomes to help regulate their maintenance or proliferation and then at midbodies during abscission
GO:0001778 plasma membrane repair	IEA GO_REF:0000117	KEEP AS NON CORE	Summary: Plausible non-core CHMP4C plasma-membrane repair ESCRT context. Reason: Plasma membrane repair is a valid ESCRT output context, but the available CHMP4C-specific evidence points to abscission-checkpoint regulation rather than plasma repair as core function. Supporting Evidence: PMID:24482116 ESCRT proteins were recruited within seconds to plasma membrane wounds PMID:24482116 repair of certain wounds is ensured by ESCRT-mediated extracellular shedding of wounded portions
GO:0005643 nuclear pore	IEA GO_REF:0000117	KEEP AS NON CORE	Summary: Plausible non-core CHMP4C nuclear-envelope ESCRT context: nuclear pore. Reason: Nuclear envelope sealing/reassembly is a supported ESCRT-III context, but it is secondary to the CHMP4C-specific abscission-checkpoint role. Supporting Evidence: PMID:26040712 ESCRT-III, VPS4 and spastin cooperate to coordinate nuclear envelope sealing and spindle disassembly PMID:26040713 ESCRT-III controls nuclear envelope reformation
GO:0005765 lysosomal membrane	IEA GO_REF:0000117	KEEP AS NON CORE	Summary: Plausible PN-relevant but non-core CHMP4C autophagy/endolysosomal context: lysosomal membrane. Reason: The PN places CHMP4C in an ESCRT-III autophagophore closure bucket and ESCRT/MVB function supports autophagic clearance, but cached CHMP4C-specific papers do not directly test CHMP4C as the phagophore sealing effector. Supporting Evidence: PMID:17984323 Functional multivesicular bodies are required for autophagic clearance PMID:17984323 autophagic degradation is inhibited in cells depleted of ESCRT subunits file:human/CHMP4C/CHMP4C-notes.md the cached CHMP4C-specific papers do not directly assay CHMP4C as the phagophore sealing effector
GO:0005828 kinetochore microtubule	IEA GO_REF:0000117	KEEP AS NON CORE	Summary: Plausible non-core CHMP4C centrosome/spindle/cell-cycle context: kinetochore microtubule. Reason: ESCRT-III/VPS4 perturbation affects centrosome and spindle maintenance, but these broad cell-cycle annotations are secondary to CHMP4C abscission-checkpoint regulation. Supporting Evidence: PMID:20616062 depletion of individual ESCRT-III and VPS4 proteins also altered centrosome and spindle pole numbers PMID:20616062 ESCRT-III/VPS4 proteins function at centrosomes to help regulate their maintenance or proliferation and then at midbodies during abscission
GO:0005829 cytosol	IEA GO_REF:0000044	KEEP AS NON CORE	Summary: True or plausible broad CHMP4C location: cytosol. Reason: This location is compatible with CHMP4C cycling between cytosol and recruited ESCRT-III assemblies, but it is too broad to represent the core function by itself. Supporting Evidence: UniProt:Q96CF2 Cytoplasm. Cytosol UniProt:Q96CF2 Localizes to the midbody during late cytokinesis
GO:0007034 vacuolar transport	IEA GO_REF:0000002	MODIFY	Summary: CHMP4C annotation should be replaced with a less over-specific ESCRT/MVB term: vacuolar transport. Reason: Vacuolar transport is too broad; if retained for CHMP4C it should be framed as general MVB sorting context, not core CHMP4C checkpoint function. Proposed replacements: multivesicular body sorting pathway Supporting Evidence: UniProt:Q96CF2 involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs PMID:18511562 The ESCRT pathway facilitates membrane fission events during enveloped virus budding, multivesicular body formation, and cytokinesis PMID:22422861 depletion of CHMP4B prevented MHC-I degradation, whereas depletion of CHMP4A or CHMP4C had little effect file:human/CHMP4C/CHMP4C-notes.md broad MVB cargo-degradation annotations for CHMP4C should be retained, at most, as non-core/over-annotated ESCRT-family context
GO:0007080 mitotic metaphase chromosome alignment	IEA GO_REF:0000117	KEEP AS NON CORE	Summary: Plausible non-core CHMP4C centrosome/spindle/cell-cycle context: mitotic metaphase chromosome alignment. Reason: ESCRT-III/VPS4 perturbation affects centrosome and spindle maintenance, but these broad cell-cycle annotations are secondary to CHMP4C abscission-checkpoint regulation. Supporting Evidence: PMID:20616062 depletion of individual ESCRT-III and VPS4 proteins also altered centrosome and spindle pole numbers PMID:20616062 ESCRT-III/VPS4 proteins function at centrosomes to help regulate their maintenance or proliferation and then at midbodies during abscission
GO:0030496 midbody	IEA GO_REF:0000117	ACCEPT	Summary: Supported core CHMP4C cytokinesis-checkpoint location: midbody. Reason: CHMP4C localizes to the midbody and Flemming body during late cytokinesis, with timing and localization tied to its Aurora B-dependent abscission-checkpoint function. Supporting Evidence: PMID:22422861 GFP-CHMP4C localized earlier to the midbody PMID:22422861 HA-CHMP4C localised to the Flemming-body in an INS-dependent manner PMID:22422861 Aurora B-dependent phosphorylation of S210 allows CHMP4C localization to the Flemming body
GO:0031468 nuclear membrane reassembly	IEA GO_REF:0000117	KEEP AS NON CORE	Summary: Plausible non-core CHMP4C nuclear-envelope ESCRT context: nuclear membrane reassembly. Reason: Nuclear envelope sealing/reassembly is a supported ESCRT-III context, but it is secondary to the CHMP4C-specific abscission-checkpoint role. Supporting Evidence: PMID:26040712 ESCRT-III, VPS4 and spastin cooperate to coordinate nuclear envelope sealing and spindle disassembly PMID:26040713 ESCRT-III controls nuclear envelope reformation
GO:0031902 late endosome membrane	IEA GO_REF:0000044	KEEP AS NON CORE	Summary: Plausible but non-core CHMP4C ESCRT/MVB context: late endosome membrane. Reason: CHMP4C belongs to the CHMP4/ESCRT-III family, but CHMP4C-specific evidence points most strongly to abscission-checkpoint regulation; MVB/endosomal sorting annotations are retained as non-core ESCRT-family context. Supporting Evidence: UniProt:Q96CF2 involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs PMID:18511562 The ESCRT pathway facilitates membrane fission events during enveloped virus budding, multivesicular body formation, and cytokinesis PMID:22422861 depletion of CHMP4B prevented MHC-I degradation, whereas depletion of CHMP4A or CHMP4C had little effect file:human/CHMP4C/CHMP4C-notes.md broad MVB cargo-degradation annotations for CHMP4C should be retained, at most, as non-core/over-annotated ESCRT-family context
GO:0032585 multivesicular body membrane	IEA GO_REF:0000117	KEEP AS NON CORE	Summary: Plausible but non-core CHMP4C ESCRT/MVB context: multivesicular body membrane. Reason: CHMP4C belongs to the CHMP4/ESCRT-III family, but CHMP4C-specific evidence points most strongly to abscission-checkpoint regulation; MVB/endosomal sorting annotations are retained as non-core ESCRT-family context. Supporting Evidence: UniProt:Q96CF2 involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs PMID:18511562 The ESCRT pathway facilitates membrane fission events during enveloped virus budding, multivesicular body formation, and cytokinesis PMID:22422861 depletion of CHMP4B prevented MHC-I degradation, whereas depletion of CHMP4A or CHMP4C had little effect file:human/CHMP4C/CHMP4C-notes.md broad MVB cargo-degradation annotations for CHMP4C should be retained, at most, as non-core/over-annotated ESCRT-family context
GO:0036258 multivesicular body assembly	IEA GO_REF:0000117	KEEP AS NON CORE	Summary: Plausible but non-core CHMP4C ESCRT/MVB context: multivesicular body assembly. Reason: CHMP4C belongs to the CHMP4/ESCRT-III family, but CHMP4C-specific evidence points most strongly to abscission-checkpoint regulation; MVB/endosomal sorting annotations are retained as non-core ESCRT-family context. Supporting Evidence: UniProt:Q96CF2 involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs PMID:18511562 The ESCRT pathway facilitates membrane fission events during enveloped virus budding, multivesicular body formation, and cytokinesis PMID:22422861 depletion of CHMP4B prevented MHC-I degradation, whereas depletion of CHMP4A or CHMP4C had little effect file:human/CHMP4C/CHMP4C-notes.md broad MVB cargo-degradation annotations for CHMP4C should be retained, at most, as non-core/over-annotated ESCRT-family context
GO:0039702 viral budding via host ESCRT complex	IEA GO_REF:0000117	MARK AS OVER ANNOTATED	Summary: Likely paralog over-annotation for CHMP4C viral budding context: viral budding via host ESCRT complex. Reason: CHMP4C can bind ESCRT/ALIX machinery, but a direct CHMP4 paralog comparison found that CHMP4A or CHMP4C depletion did not inhibit HIV-1 release whereas CHMP4B depletion did; viral budding should not be treated as a CHMP4C core role. Supporting Evidence: PMID:22422861 depletion of CHMP4A or CHMP4C did not inhibit HIV-1 release PMID:22422861 only depletion of CHMP4B inhibited this ESCRT-dependent process file:human/CHMP4C/CHMP4C-notes.md Viral budding annotations are also likely paralog over-annotations for CHMP4C
GO:0042803 protein homodimerization activity	IEA GO_REF:0000117	MARK AS OVER ANNOTATED	Summary: Over-annotated CHMP4C molecular-function annotation: protein homodimerization activity. Reason: The interaction evidence is real in some cases, but generic binding or homodimerization does not capture the informative CHMP4C function: ESCRT-III abscission-checkpoint regulation through Aurora B/CPC/ANCHR/VPS4-associated assemblies. Supporting Evidence: PMID:18511562 Bro1 domain of ALIX binds specifically to C-terminal residues of the human CHMP4 proteins (CHMP4A-C) PMID:36107470 CHMP4C performs a unique role in abscission checkpoint regulation file:human/CHMP4C/CHMP4C-notes.md Generic protein binding and homodimerization annotations are over-annotated.
GO:0043162 ubiquitin-dependent protein catabolic process via the multivesicular body sorting pathway	IEA GO_REF:0000117	KEEP AS NON CORE	Summary: Plausible but non-core CHMP4C ESCRT/MVB context: ubiquitin-dependent protein catabolic process via the multivesicular body sorting pathway. Reason: CHMP4C belongs to the CHMP4/ESCRT-III family, but CHMP4C-specific evidence points most strongly to abscission-checkpoint regulation; MVB/endosomal sorting annotations are retained as non-core ESCRT-family context. Supporting Evidence: UniProt:Q96CF2 involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs PMID:18511562 The ESCRT pathway facilitates membrane fission events during enveloped virus budding, multivesicular body formation, and cytokinesis PMID:22422861 depletion of CHMP4B prevented MHC-I degradation, whereas depletion of CHMP4A or CHMP4C had little effect file:human/CHMP4C/CHMP4C-notes.md broad MVB cargo-degradation annotations for CHMP4C should be retained, at most, as non-core/over-annotated ESCRT-family context
GO:0046761 viral budding from plasma membrane	IEA GO_REF:0000117	MARK AS OVER ANNOTATED	Summary: Likely paralog over-annotation for CHMP4C viral budding context: viral budding from plasma membrane. Reason: CHMP4C can bind ESCRT/ALIX machinery, but a direct CHMP4 paralog comparison found that CHMP4A or CHMP4C depletion did not inhibit HIV-1 release whereas CHMP4B depletion did; viral budding should not be treated as a CHMP4C core role. Supporting Evidence: PMID:22422861 depletion of CHMP4A or CHMP4C did not inhibit HIV-1 release PMID:22422861 only depletion of CHMP4B inhibited this ESCRT-dependent process file:human/CHMP4C/CHMP4C-notes.md Viral budding annotations are also likely paralog over-annotations for CHMP4C
GO:0061952 midbody abscission	IEA GO_REF:0000117	ACCEPT	Summary: Supported core CHMP4C abscission-checkpoint annotation: midbody abscission. Reason: CHMP4C is a specialized ESCRT-III regulatory subunit for Aurora B/NoCut abscission checkpoint control, delaying abscission through phosphorylation-dependent localization and ANCHR/VPS4 retention at the midbody. Supporting Evidence: UniProt:Q96CF2 component of the cytokinesis checkpoint UniProt:Q96CF2 retains abscission-competent VPS4 PMID:22422861 CHMP4C functioned in the Aurora B-dependent abscission checkpoint PMID:22422861 depletion of CHMP4C reduced abscission time by approximately 30 minutes PMID:22422861 CHMP4C depletion circumvents the NoCut abscission checkpoint PMID:24814515 In concert with CHMP4C, ANCHR associates with VPS4 at the midbody ring PMID:24814515 abscission checkpoint is mediated by ANCHR and CHMP4C through retention of VPS4 at the midbody ring PMID:22724069 Borealin interacts directly with the Snf7 components of ESCRT-III PMID:22724069 phosphorylates one of the three human Snf7 paralogues-CHMP4C
GO:0071985 multivesicular body sorting pathway	IEA GO_REF:0000117	KEEP AS NON CORE	Summary: Plausible but non-core CHMP4C ESCRT/MVB context: multivesicular body sorting pathway. Reason: CHMP4C belongs to the CHMP4/ESCRT-III family, but CHMP4C-specific evidence points most strongly to abscission-checkpoint regulation; MVB/endosomal sorting annotations are retained as non-core ESCRT-family context. Supporting Evidence: UniProt:Q96CF2 involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs PMID:18511562 The ESCRT pathway facilitates membrane fission events during enveloped virus budding, multivesicular body formation, and cytokinesis PMID:22422861 depletion of CHMP4B prevented MHC-I degradation, whereas depletion of CHMP4A or CHMP4C had little effect file:human/CHMP4C/CHMP4C-notes.md broad MVB cargo-degradation annotations for CHMP4C should be retained, at most, as non-core/over-annotated ESCRT-family context
GO:0090543 Flemming body	IEA GO_REF:0000044	ACCEPT	Summary: Supported core CHMP4C cytokinesis-checkpoint location: Flemming body. Reason: CHMP4C localizes to the midbody and Flemming body during late cytokinesis, with timing and localization tied to its Aurora B-dependent abscission-checkpoint function. Supporting Evidence: PMID:22422861 GFP-CHMP4C localized earlier to the midbody PMID:22422861 HA-CHMP4C localised to the Flemming-body in an INS-dependent manner PMID:22422861 Aurora B-dependent phosphorylation of S210 allows CHMP4C localization to the Flemming body
GO:0097352 autophagosome maturation	IEA GO_REF:0000117	KEEP AS NON CORE	Summary: Plausible PN-relevant but non-core CHMP4C autophagy/endolysosomal context: autophagosome maturation. Reason: The PN places CHMP4C in an ESCRT-III autophagophore closure bucket and ESCRT/MVB function supports autophagic clearance, but cached CHMP4C-specific papers do not directly test CHMP4C as the phagophore sealing effector. Supporting Evidence: PMID:17984323 Functional multivesicular bodies are required for autophagic clearance PMID:17984323 autophagic degradation is inhibited in cells depleted of ESCRT subunits file:human/CHMP4C/CHMP4C-notes.md the cached CHMP4C-specific papers do not directly assay CHMP4C as the phagophore sealing effector
GO:1901673 regulation of mitotic spindle assembly	IEA GO_REF:0000117	KEEP AS NON CORE	Summary: Plausible non-core CHMP4C centrosome/spindle/cell-cycle context: regulation of mitotic spindle assembly. Reason: ESCRT-III/VPS4 perturbation affects centrosome and spindle maintenance, but these broad cell-cycle annotations are secondary to CHMP4C abscission-checkpoint regulation. Supporting Evidence: PMID:20616062 depletion of individual ESCRT-III and VPS4 proteins also altered centrosome and spindle pole numbers PMID:20616062 ESCRT-III/VPS4 proteins function at centrosomes to help regulate their maintenance or proliferation and then at midbodies during abscission
GO:1902774 late endosome to lysosome transport	IEA GO_REF:0000117	KEEP AS NON CORE	Summary: Plausible but non-core CHMP4C ESCRT/MVB context: late endosome to lysosome transport. Reason: CHMP4C belongs to the CHMP4/ESCRT-III family, but CHMP4C-specific evidence points most strongly to abscission-checkpoint regulation; MVB/endosomal sorting annotations are retained as non-core ESCRT-family context. Supporting Evidence: UniProt:Q96CF2 involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs PMID:18511562 The ESCRT pathway facilitates membrane fission events during enveloped virus budding, multivesicular body formation, and cytokinesis PMID:22422861 depletion of CHMP4B prevented MHC-I degradation, whereas depletion of CHMP4A or CHMP4C had little effect file:human/CHMP4C/CHMP4C-notes.md broad MVB cargo-degradation annotations for CHMP4C should be retained, at most, as non-core/over-annotated ESCRT-family context
GO:1904930 amphisome membrane	IEA GO_REF:0000117	KEEP AS NON CORE	Summary: Plausible PN-relevant but non-core CHMP4C autophagy/endolysosomal context: amphisome membrane. Reason: The PN places CHMP4C in an ESCRT-III autophagophore closure bucket and ESCRT/MVB function supports autophagic clearance, but cached CHMP4C-specific papers do not directly test CHMP4C as the phagophore sealing effector. Supporting Evidence: PMID:17984323 Functional multivesicular bodies are required for autophagic clearance PMID:17984323 autophagic degradation is inhibited in cells depleted of ESCRT subunits file:human/CHMP4C/CHMP4C-notes.md the cached CHMP4C-specific papers do not directly assay CHMP4C as the phagophore sealing effector
GO:0005515 protein binding	IPI PMID:17711858 The MIT domain of UBPY constitutes a CHMP binding and endoso...	MARK AS OVER ANNOTATED	Summary: Over-annotated CHMP4C molecular-function annotation: protein binding. Reason: The interaction evidence is real in some cases, but generic binding or homodimerization does not capture the informative CHMP4C function: ESCRT-III abscission-checkpoint regulation through Aurora B/CPC/ANCHR/VPS4-associated assemblies. Supporting Evidence: PMID:18511562 Bro1 domain of ALIX binds specifically to C-terminal residues of the human CHMP4 proteins (CHMP4A-C) PMID:36107470 CHMP4C performs a unique role in abscission checkpoint regulation file:human/CHMP4C/CHMP4C-notes.md Generic protein binding and homodimerization annotations are over-annotated.
GO:0005515 protein binding	IPI PMID:18511562 ALIX-CHMP4 interactions in the human ESCRT pathway.	MARK AS OVER ANNOTATED	Summary: Over-annotated CHMP4C molecular-function annotation: protein binding. Reason: The interaction evidence is real in some cases, but generic binding or homodimerization does not capture the informative CHMP4C function: ESCRT-III abscission-checkpoint regulation through Aurora B/CPC/ANCHR/VPS4-associated assemblies. Supporting Evidence: PMID:18511562 Bro1 domain of ALIX binds specifically to C-terminal residues of the human CHMP4 proteins (CHMP4A-C) PMID:36107470 CHMP4C performs a unique role in abscission checkpoint regulation file:human/CHMP4C/CHMP4C-notes.md Generic protein binding and homodimerization annotations are over-annotated.
GO:0005515 protein binding	IPI PMID:19302785 Ab initio protein modelling reveals novel human MIT domains.	MARK AS OVER ANNOTATED	Summary: Over-annotated CHMP4C molecular-function annotation: protein binding. Reason: The interaction evidence is real in some cases, but generic binding or homodimerization does not capture the informative CHMP4C function: ESCRT-III abscission-checkpoint regulation through Aurora B/CPC/ANCHR/VPS4-associated assemblies. Supporting Evidence: PMID:18511562 Bro1 domain of ALIX binds specifically to C-terminal residues of the human CHMP4 proteins (CHMP4A-C) PMID:36107470 CHMP4C performs a unique role in abscission checkpoint regulation file:human/CHMP4C/CHMP4C-notes.md Generic protein binding and homodimerization annotations are over-annotated.
GO:0005515 protein binding	IPI PMID:21988832 Toward an understanding of the protein interaction network o...	MARK AS OVER ANNOTATED	Summary: Over-annotated CHMP4C molecular-function annotation: protein binding. Reason: The interaction evidence is real in some cases, but generic binding or homodimerization does not capture the informative CHMP4C function: ESCRT-III abscission-checkpoint regulation through Aurora B/CPC/ANCHR/VPS4-associated assemblies. Supporting Evidence: PMID:18511562 Bro1 domain of ALIX binds specifically to C-terminal residues of the human CHMP4 proteins (CHMP4A-C) PMID:36107470 CHMP4C performs a unique role in abscission checkpoint regulation file:human/CHMP4C/CHMP4C-notes.md Generic protein binding and homodimerization annotations are over-annotated.
GO:0000421 autophagosome membrane	IDA PMID:17984323 Functional multivesicular bodies are required for autophagic...	KEEP AS NON CORE	Summary: Plausible PN-relevant but non-core CHMP4C autophagy/endolysosomal context: autophagosome membrane. Reason: The PN places CHMP4C in an ESCRT-III autophagophore closure bucket and ESCRT/MVB function supports autophagic clearance, but cached CHMP4C-specific papers do not directly test CHMP4C as the phagophore sealing effector. Supporting Evidence: PMID:17984323 Functional multivesicular bodies are required for autophagic clearance PMID:17984323 autophagic degradation is inhibited in cells depleted of ESCRT subunits file:human/CHMP4C/CHMP4C-notes.md the cached CHMP4C-specific papers do not directly assay CHMP4C as the phagophore sealing effector
GO:0000776 kinetochore	IDA PMID:26040712 Spastin and ESCRT-III coordinate mitotic spindle disassembly...	KEEP AS NON CORE	Summary: Plausible non-core CHMP4C centrosome/spindle/cell-cycle context: kinetochore. Reason: ESCRT-III/VPS4 perturbation affects centrosome and spindle maintenance, but these broad cell-cycle annotations are secondary to CHMP4C abscission-checkpoint regulation. Supporting Evidence: PMID:20616062 depletion of individual ESCRT-III and VPS4 proteins also altered centrosome and spindle pole numbers PMID:20616062 ESCRT-III/VPS4 proteins function at centrosomes to help regulate their maintenance or proliferation and then at midbodies during abscission
GO:0000815 ESCRT III complex	NAS PMID:36107470 Comprehensive analysis of the human ESCRT-III-MIT domain int...	ACCEPT	Summary: Supported CHMP4C ESCRT-III complex membership annotation: ESCRT III complex. Reason: CHMP4C is a Snf7-family CHMP4 subunit of ESCRT-III; its most specific cellular function is checkpoint regulation, but complex membership is sound. Supporting Evidence: UniProt:Q96CF2 Probable core component of the endosomal sorting required for transport complex III (ESCRT-III) UniProt:Q96CF2 ESCRT-III proteins mostly dissociate from the invaginating membrane before the ILV is released PMID:18511562 Bro1 domain of ALIX binds specifically to C-terminal residues of the human CHMP4 proteins (CHMP4A-C) PMID:36107470 CHMP4C performs a unique role in abscission checkpoint regulation file:human/CHMP4C/CHMP4C-notes.md CHMP4C still has bona fide ESCRT-III context.
GO:0001778 plasma membrane repair	IDA PMID:24482116 ESCRT machinery is required for plasma membrane repair.	KEEP AS NON CORE	Summary: Plausible non-core CHMP4C plasma-membrane repair ESCRT context. Reason: Plasma membrane repair is a valid ESCRT output context, but the available CHMP4C-specific evidence points to abscission-checkpoint regulation rather than plasma repair as core function. Supporting Evidence: PMID:24482116 ESCRT proteins were recruited within seconds to plasma membrane wounds PMID:24482116 repair of certain wounds is ensured by ESCRT-mediated extracellular shedding of wounded portions
GO:0005643 nuclear pore	IDA PMID:26040713 ESCRT-III controls nuclear envelope reformation.	KEEP AS NON CORE	Summary: Plausible non-core CHMP4C nuclear-envelope ESCRT context: nuclear pore. Reason: Nuclear envelope sealing/reassembly is a supported ESCRT-III context, but it is secondary to the CHMP4C-specific abscission-checkpoint role. Supporting Evidence: PMID:26040712 ESCRT-III, VPS4 and spastin cooperate to coordinate nuclear envelope sealing and spindle disassembly PMID:26040713 ESCRT-III controls nuclear envelope reformation
GO:0005765 lysosomal membrane	IDA PMID:17984323 Functional multivesicular bodies are required for autophagic...	KEEP AS NON CORE	Summary: Plausible PN-relevant but non-core CHMP4C autophagy/endolysosomal context: lysosomal membrane. Reason: The PN places CHMP4C in an ESCRT-III autophagophore closure bucket and ESCRT/MVB function supports autophagic clearance, but cached CHMP4C-specific papers do not directly test CHMP4C as the phagophore sealing effector. Supporting Evidence: PMID:17984323 Functional multivesicular bodies are required for autophagic clearance PMID:17984323 autophagic degradation is inhibited in cells depleted of ESCRT subunits file:human/CHMP4C/CHMP4C-notes.md the cached CHMP4C-specific papers do not directly assay CHMP4C as the phagophore sealing effector
GO:0005828 kinetochore microtubule	IDA PMID:26040712 Spastin and ESCRT-III coordinate mitotic spindle disassembly...	KEEP AS NON CORE	Summary: Plausible non-core CHMP4C centrosome/spindle/cell-cycle context: kinetochore microtubule. Reason: ESCRT-III/VPS4 perturbation affects centrosome and spindle maintenance, but these broad cell-cycle annotations are secondary to CHMP4C abscission-checkpoint regulation. Supporting Evidence: PMID:20616062 depletion of individual ESCRT-III and VPS4 proteins also altered centrosome and spindle pole numbers PMID:20616062 ESCRT-III/VPS4 proteins function at centrosomes to help regulate their maintenance or proliferation and then at midbodies during abscission
GO:0005886 plasma membrane	IDA PMID:24878737 Structure of cellular ESCRT-III spirals and their relationsh...	KEEP AS NON CORE	Summary: True or plausible broad CHMP4C location: plasma membrane. Reason: This location is compatible with CHMP4C cycling between cytosol and recruited ESCRT-III assemblies, but it is too broad to represent the core function by itself. Supporting Evidence: UniProt:Q96CF2 Cytoplasm. Cytosol UniProt:Q96CF2 Localizes to the midbody during late cytokinesis
GO:0006914 autophagy	IMP PMID:17984323 Functional multivesicular bodies are required for autophagic...	KEEP AS NON CORE	Summary: Plausible PN-relevant but non-core CHMP4C autophagy/endolysosomal context: autophagy. Reason: The PN places CHMP4C in an ESCRT-III autophagophore closure bucket and ESCRT/MVB function supports autophagic clearance, but cached CHMP4C-specific papers do not directly test CHMP4C as the phagophore sealing effector. Supporting Evidence: PMID:17984323 Functional multivesicular bodies are required for autophagic clearance PMID:17984323 autophagic degradation is inhibited in cells depleted of ESCRT subunits file:human/CHMP4C/CHMP4C-notes.md the cached CHMP4C-specific papers do not directly assay CHMP4C as the phagophore sealing effector
GO:0006997 nucleus organization	IMP PMID:20616062 Human ESCRT-III and VPS4 proteins are required for centrosom...	KEEP AS NON CORE	Summary: Plausible non-core CHMP4C centrosome/spindle/cell-cycle context: nucleus organization. Reason: ESCRT-III/VPS4 perturbation affects centrosome and spindle maintenance, but these broad cell-cycle annotations are secondary to CHMP4C abscission-checkpoint regulation. Supporting Evidence: PMID:20616062 depletion of individual ESCRT-III and VPS4 proteins also altered centrosome and spindle pole numbers PMID:20616062 ESCRT-III/VPS4 proteins function at centrosomes to help regulate their maintenance or proliferation and then at midbodies during abscission
GO:0007080 mitotic metaphase chromosome alignment	IMP PMID:20616062 Human ESCRT-III and VPS4 proteins are required for centrosom...	KEEP AS NON CORE	Summary: Plausible non-core CHMP4C centrosome/spindle/cell-cycle context: mitotic metaphase chromosome alignment. Reason: ESCRT-III/VPS4 perturbation affects centrosome and spindle maintenance, but these broad cell-cycle annotations are secondary to CHMP4C abscission-checkpoint regulation. Supporting Evidence: PMID:20616062 depletion of individual ESCRT-III and VPS4 proteins also altered centrosome and spindle pole numbers PMID:20616062 ESCRT-III/VPS4 proteins function at centrosomes to help regulate their maintenance or proliferation and then at midbodies during abscission
GO:0030496 midbody	IDA PMID:26040712 Spastin and ESCRT-III coordinate mitotic spindle disassembly...	ACCEPT	Summary: Supported core CHMP4C cytokinesis-checkpoint location: midbody. Reason: CHMP4C localizes to the midbody and Flemming body during late cytokinesis, with timing and localization tied to its Aurora B-dependent abscission-checkpoint function. Supporting Evidence: PMID:22422861 GFP-CHMP4C localized earlier to the midbody PMID:22422861 HA-CHMP4C localised to the Flemming-body in an INS-dependent manner PMID:22422861 Aurora B-dependent phosphorylation of S210 allows CHMP4C localization to the Flemming body
GO:0031468 nuclear membrane reassembly	IMP PMID:26040713 ESCRT-III controls nuclear envelope reformation.	KEEP AS NON CORE	Summary: Plausible non-core CHMP4C nuclear-envelope ESCRT context: nuclear membrane reassembly. Reason: Nuclear envelope sealing/reassembly is a supported ESCRT-III context, but it is secondary to the CHMP4C-specific abscission-checkpoint role. Supporting Evidence: PMID:26040712 ESCRT-III, VPS4 and spastin cooperate to coordinate nuclear envelope sealing and spindle disassembly PMID:26040713 ESCRT-III controls nuclear envelope reformation
GO:0032585 multivesicular body membrane	IDA PMID:16554368 The ESCRT-III subunit hVps24 is required for degradation but...	KEEP AS NON CORE	Summary: Plausible but non-core CHMP4C ESCRT/MVB context: multivesicular body membrane. Reason: CHMP4C belongs to the CHMP4/ESCRT-III family, but CHMP4C-specific evidence points most strongly to abscission-checkpoint regulation; MVB/endosomal sorting annotations are retained as non-core ESCRT-family context. Supporting Evidence: UniProt:Q96CF2 involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs PMID:18511562 The ESCRT pathway facilitates membrane fission events during enveloped virus budding, multivesicular body formation, and cytokinesis PMID:22422861 depletion of CHMP4B prevented MHC-I degradation, whereas depletion of CHMP4A or CHMP4C had little effect file:human/CHMP4C/CHMP4C-notes.md broad MVB cargo-degradation annotations for CHMP4C should be retained, at most, as non-core/over-annotated ESCRT-family context
GO:0036258 multivesicular body assembly	NAS PMID:16505166 Recycling of ESCRTs by the AAA-ATPase Vps4 is regulated by a...	KEEP AS NON CORE	Summary: Plausible but non-core CHMP4C ESCRT/MVB context: multivesicular body assembly. Reason: CHMP4C belongs to the CHMP4/ESCRT-III family, but CHMP4C-specific evidence points most strongly to abscission-checkpoint regulation; MVB/endosomal sorting annotations are retained as non-core ESCRT-family context. Supporting Evidence: UniProt:Q96CF2 involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs PMID:18511562 The ESCRT pathway facilitates membrane fission events during enveloped virus budding, multivesicular body formation, and cytokinesis PMID:22422861 depletion of CHMP4B prevented MHC-I degradation, whereas depletion of CHMP4A or CHMP4C had little effect file:human/CHMP4C/CHMP4C-notes.md broad MVB cargo-degradation annotations for CHMP4C should be retained, at most, as non-core/over-annotated ESCRT-family context
GO:0039702 viral budding via host ESCRT complex	IDA PMID:24878737 Structure of cellular ESCRT-III spirals and their relationsh...	MARK AS OVER ANNOTATED	Summary: Likely paralog over-annotation for CHMP4C viral budding context: viral budding via host ESCRT complex. Reason: CHMP4C can bind ESCRT/ALIX machinery, but a direct CHMP4 paralog comparison found that CHMP4A or CHMP4C depletion did not inhibit HIV-1 release whereas CHMP4B depletion did; viral budding should not be treated as a CHMP4C core role. Supporting Evidence: PMID:22422861 depletion of CHMP4A or CHMP4C did not inhibit HIV-1 release PMID:22422861 only depletion of CHMP4B inhibited this ESCRT-dependent process file:human/CHMP4C/CHMP4C-notes.md Viral budding annotations are also likely paralog over-annotations for CHMP4C
GO:0043162 ubiquitin-dependent protein catabolic process via the multivesicular body sorting pathway	IDA PMID:17984323 Functional multivesicular bodies are required for autophagic...	KEEP AS NON CORE	Summary: Plausible but non-core CHMP4C ESCRT/MVB context: ubiquitin-dependent protein catabolic process via the multivesicular body sorting pathway. Reason: CHMP4C belongs to the CHMP4/ESCRT-III family, but CHMP4C-specific evidence points most strongly to abscission-checkpoint regulation; MVB/endosomal sorting annotations are retained as non-core ESCRT-family context. Supporting Evidence: UniProt:Q96CF2 involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs PMID:18511562 The ESCRT pathway facilitates membrane fission events during enveloped virus budding, multivesicular body formation, and cytokinesis PMID:22422861 depletion of CHMP4B prevented MHC-I degradation, whereas depletion of CHMP4A or CHMP4C had little effect file:human/CHMP4C/CHMP4C-notes.md broad MVB cargo-degradation annotations for CHMP4C should be retained, at most, as non-core/over-annotated ESCRT-family context
GO:0046761 viral budding from plasma membrane	IDA PMID:24878737 Structure of cellular ESCRT-III spirals and their relationsh...	MARK AS OVER ANNOTATED	Summary: Likely paralog over-annotation for CHMP4C viral budding context: viral budding from plasma membrane. Reason: CHMP4C can bind ESCRT/ALIX machinery, but a direct CHMP4 paralog comparison found that CHMP4A or CHMP4C depletion did not inhibit HIV-1 release whereas CHMP4B depletion did; viral budding should not be treated as a CHMP4C core role. Supporting Evidence: PMID:22422861 depletion of CHMP4A or CHMP4C did not inhibit HIV-1 release PMID:22422861 only depletion of CHMP4B inhibited this ESCRT-dependent process file:human/CHMP4C/CHMP4C-notes.md Viral budding annotations are also likely paralog over-annotations for CHMP4C
GO:0051469 vesicle fusion with vacuole	NAS PMID:16505166 Recycling of ESCRTs by the AAA-ATPase Vps4 is regulated by a...	MODIFY	Summary: CHMP4C annotation should be replaced with a less over-specific ESCRT/MVB term: vesicle fusion with vacuole. Reason: The evidence supports ESCRT/MVB trafficking context rather than CHMP4C acting as a vesicle-vacuole fusion factor. Proposed replacements: late endosome to lysosome transport Supporting Evidence: UniProt:Q96CF2 involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs PMID:18511562 The ESCRT pathway facilitates membrane fission events during enveloped virus budding, multivesicular body formation, and cytokinesis PMID:22422861 depletion of CHMP4B prevented MHC-I degradation, whereas depletion of CHMP4A or CHMP4C had little effect file:human/CHMP4C/CHMP4C-notes.md broad MVB cargo-degradation annotations for CHMP4C should be retained, at most, as non-core/over-annotated ESCRT-family context
GO:0061763 multivesicular body-lysosome fusion	NAS PMID:16505166 Recycling of ESCRTs by the AAA-ATPase Vps4 is regulated by a...	MODIFY	Summary: CHMP4C annotation should be replaced with a less over-specific ESCRT/MVB term: multivesicular body-lysosome fusion. Reason: The evidence supports late endosome-to-lysosome/endolysosomal transport context rather than CHMP4C as a direct MVB-lysosome fusion factor. Proposed replacements: late endosome to lysosome transport Supporting Evidence: UniProt:Q96CF2 involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs PMID:18511562 The ESCRT pathway facilitates membrane fission events during enveloped virus budding, multivesicular body formation, and cytokinesis PMID:22422861 depletion of CHMP4B prevented MHC-I degradation, whereas depletion of CHMP4A or CHMP4C had little effect file:human/CHMP4C/CHMP4C-notes.md broad MVB cargo-degradation annotations for CHMP4C should be retained, at most, as non-core/over-annotated ESCRT-family context
GO:0061952 midbody abscission	IMP PMID:20616062 Human ESCRT-III and VPS4 proteins are required for centrosom...	ACCEPT	Summary: Supported core CHMP4C abscission-checkpoint annotation: midbody abscission. Reason: CHMP4C is a specialized ESCRT-III regulatory subunit for Aurora B/NoCut abscission checkpoint control, delaying abscission through phosphorylation-dependent localization and ANCHR/VPS4 retention at the midbody. Supporting Evidence: UniProt:Q96CF2 component of the cytokinesis checkpoint UniProt:Q96CF2 retains abscission-competent VPS4 PMID:22422861 CHMP4C functioned in the Aurora B-dependent abscission checkpoint PMID:22422861 depletion of CHMP4C reduced abscission time by approximately 30 minutes PMID:22422861 CHMP4C depletion circumvents the NoCut abscission checkpoint PMID:24814515 In concert with CHMP4C, ANCHR associates with VPS4 at the midbody ring PMID:24814515 abscission checkpoint is mediated by ANCHR and CHMP4C through retention of VPS4 at the midbody ring PMID:22724069 Borealin interacts directly with the Snf7 components of ESCRT-III PMID:22724069 phosphorylates one of the three human Snf7 paralogues-CHMP4C
GO:0071985 multivesicular body sorting pathway	IDA PMID:16554368 The ESCRT-III subunit hVps24 is required for degradation but...	KEEP AS NON CORE	Summary: Plausible but non-core CHMP4C ESCRT/MVB context: multivesicular body sorting pathway. Reason: CHMP4C belongs to the CHMP4/ESCRT-III family, but CHMP4C-specific evidence points most strongly to abscission-checkpoint regulation; MVB/endosomal sorting annotations are retained as non-core ESCRT-family context. Supporting Evidence: UniProt:Q96CF2 involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs PMID:18511562 The ESCRT pathway facilitates membrane fission events during enveloped virus budding, multivesicular body formation, and cytokinesis PMID:22422861 depletion of CHMP4B prevented MHC-I degradation, whereas depletion of CHMP4A or CHMP4C had little effect file:human/CHMP4C/CHMP4C-notes.md broad MVB cargo-degradation annotations for CHMP4C should be retained, at most, as non-core/over-annotated ESCRT-family context
GO:0090148 membrane fission	NAS PMID:19234443 Membrane scission by the ESCRT-III complex.	KEEP AS NON CORE	Summary: Plausible but non-core CHMP4C ESCRT/MVB context: membrane fission. Reason: CHMP4C belongs to the CHMP4/ESCRT-III family, but CHMP4C-specific evidence points most strongly to abscission-checkpoint regulation; MVB/endosomal sorting annotations are retained as non-core ESCRT-family context. Supporting Evidence: UniProt:Q96CF2 involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs PMID:18511562 The ESCRT pathway facilitates membrane fission events during enveloped virus budding, multivesicular body formation, and cytokinesis PMID:22422861 depletion of CHMP4B prevented MHC-I degradation, whereas depletion of CHMP4A or CHMP4C had little effect file:human/CHMP4C/CHMP4C-notes.md broad MVB cargo-degradation annotations for CHMP4C should be retained, at most, as non-core/over-annotated ESCRT-family context
GO:0097352 autophagosome maturation	IMP PMID:17984323 Functional multivesicular bodies are required for autophagic...	KEEP AS NON CORE	Summary: Plausible PN-relevant but non-core CHMP4C autophagy/endolysosomal context: autophagosome maturation. Reason: The PN places CHMP4C in an ESCRT-III autophagophore closure bucket and ESCRT/MVB function supports autophagic clearance, but cached CHMP4C-specific papers do not directly test CHMP4C as the phagophore sealing effector. Supporting Evidence: PMID:17984323 Functional multivesicular bodies are required for autophagic clearance PMID:17984323 autophagic degradation is inhibited in cells depleted of ESCRT subunits file:human/CHMP4C/CHMP4C-notes.md the cached CHMP4C-specific papers do not directly assay CHMP4C as the phagophore sealing effector
GO:1901673 regulation of mitotic spindle assembly	IMP PMID:20616062 Human ESCRT-III and VPS4 proteins are required for centrosom...	KEEP AS NON CORE	Summary: Plausible non-core CHMP4C centrosome/spindle/cell-cycle context: regulation of mitotic spindle assembly. Reason: ESCRT-III/VPS4 perturbation affects centrosome and spindle maintenance, but these broad cell-cycle annotations are secondary to CHMP4C abscission-checkpoint regulation. Supporting Evidence: PMID:20616062 depletion of individual ESCRT-III and VPS4 proteins also altered centrosome and spindle pole numbers PMID:20616062 ESCRT-III/VPS4 proteins function at centrosomes to help regulate their maintenance or proliferation and then at midbodies during abscission
GO:1902774 late endosome to lysosome transport	IMP PMID:17984323 Functional multivesicular bodies are required for autophagic...	KEEP AS NON CORE	Summary: Plausible but non-core CHMP4C ESCRT/MVB context: late endosome to lysosome transport. Reason: CHMP4C belongs to the CHMP4/ESCRT-III family, but CHMP4C-specific evidence points most strongly to abscission-checkpoint regulation; MVB/endosomal sorting annotations are retained as non-core ESCRT-family context. Supporting Evidence: UniProt:Q96CF2 involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs PMID:18511562 The ESCRT pathway facilitates membrane fission events during enveloped virus budding, multivesicular body formation, and cytokinesis PMID:22422861 depletion of CHMP4B prevented MHC-I degradation, whereas depletion of CHMP4A or CHMP4C had little effect file:human/CHMP4C/CHMP4C-notes.md broad MVB cargo-degradation annotations for CHMP4C should be retained, at most, as non-core/over-annotated ESCRT-family context
GO:1904930 amphisome membrane	IDA PMID:17984323 Functional multivesicular bodies are required for autophagic...	KEEP AS NON CORE	Summary: Plausible PN-relevant but non-core CHMP4C autophagy/endolysosomal context: amphisome membrane. Reason: The PN places CHMP4C in an ESCRT-III autophagophore closure bucket and ESCRT/MVB function supports autophagic clearance, but cached CHMP4C-specific papers do not directly test CHMP4C as the phagophore sealing effector. Supporting Evidence: PMID:17984323 Functional multivesicular bodies are required for autophagic clearance PMID:17984323 autophagic degradation is inhibited in cells depleted of ESCRT subunits file:human/CHMP4C/CHMP4C-notes.md the cached CHMP4C-specific papers do not directly assay CHMP4C as the phagophore sealing effector
GO:0061952 midbody abscission	IMP PMID:22422861 ESCRT-III governs the Aurora B-mediated abscission checkpoin...	ACCEPT	Summary: Supported core CHMP4C abscission-checkpoint annotation: midbody abscission. Reason: CHMP4C is a specialized ESCRT-III regulatory subunit for Aurora B/NoCut abscission checkpoint control, delaying abscission through phosphorylation-dependent localization and ANCHR/VPS4 retention at the midbody. Supporting Evidence: UniProt:Q96CF2 component of the cytokinesis checkpoint UniProt:Q96CF2 retains abscission-competent VPS4 PMID:22422861 CHMP4C functioned in the Aurora B-dependent abscission checkpoint PMID:22422861 depletion of CHMP4C reduced abscission time by approximately 30 minutes PMID:22422861 CHMP4C depletion circumvents the NoCut abscission checkpoint PMID:24814515 In concert with CHMP4C, ANCHR associates with VPS4 at the midbody ring PMID:24814515 abscission checkpoint is mediated by ANCHR and CHMP4C through retention of VPS4 at the midbody ring PMID:22724069 Borealin interacts directly with the Snf7 components of ESCRT-III PMID:22724069 phosphorylates one of the three human Snf7 paralogues-CHMP4C
GO:0061952 midbody abscission	IMP PMID:24814515 ANCHR mediates Aurora-B-dependent abscission checkpoint cont...	ACCEPT	Summary: Supported core CHMP4C abscission-checkpoint annotation: midbody abscission. Reason: CHMP4C is a specialized ESCRT-III regulatory subunit for Aurora B/NoCut abscission checkpoint control, delaying abscission through phosphorylation-dependent localization and ANCHR/VPS4 retention at the midbody. Supporting Evidence: UniProt:Q96CF2 component of the cytokinesis checkpoint UniProt:Q96CF2 retains abscission-competent VPS4 PMID:22422861 CHMP4C functioned in the Aurora B-dependent abscission checkpoint PMID:22422861 depletion of CHMP4C reduced abscission time by approximately 30 minutes PMID:22422861 CHMP4C depletion circumvents the NoCut abscission checkpoint PMID:24814515 In concert with CHMP4C, ANCHR associates with VPS4 at the midbody ring PMID:24814515 abscission checkpoint is mediated by ANCHR and CHMP4C through retention of VPS4 at the midbody ring PMID:22724069 Borealin interacts directly with the Snf7 components of ESCRT-III PMID:22724069 phosphorylates one of the three human Snf7 paralogues-CHMP4C
GO:0046761 viral budding from plasma membrane	IMP PMID:14505570 The protein network of HIV budding.	MARK AS OVER ANNOTATED	Summary: Likely paralog over-annotation for CHMP4C viral budding context: viral budding from plasma membrane. Reason: CHMP4C can bind ESCRT/ALIX machinery, but a direct CHMP4 paralog comparison found that CHMP4A or CHMP4C depletion did not inhibit HIV-1 release whereas CHMP4B depletion did; viral budding should not be treated as a CHMP4C core role. Supporting Evidence: PMID:22422861 depletion of CHMP4A or CHMP4C did not inhibit HIV-1 release PMID:22422861 only depletion of CHMP4B inhibited this ESCRT-dependent process file:human/CHMP4C/CHMP4C-notes.md Viral budding annotations are also likely paralog over-annotations for CHMP4C
GO:0044878 mitotic cytokinesis checkpoint signaling	IMP PMID:22422861 ESCRT-III governs the Aurora B-mediated abscission checkpoin...	ACCEPT	Summary: Supported core CHMP4C abscission-checkpoint annotation: mitotic cytokinesis checkpoint signaling. Reason: CHMP4C is a specialized ESCRT-III regulatory subunit for Aurora B/NoCut abscission checkpoint control, delaying abscission through phosphorylation-dependent localization and ANCHR/VPS4 retention at the midbody. Supporting Evidence: UniProt:Q96CF2 component of the cytokinesis checkpoint UniProt:Q96CF2 retains abscission-competent VPS4 PMID:22422861 CHMP4C functioned in the Aurora B-dependent abscission checkpoint PMID:22422861 depletion of CHMP4C reduced abscission time by approximately 30 minutes PMID:22422861 CHMP4C depletion circumvents the NoCut abscission checkpoint PMID:24814515 In concert with CHMP4C, ANCHR associates with VPS4 at the midbody ring PMID:24814515 abscission checkpoint is mediated by ANCHR and CHMP4C through retention of VPS4 at the midbody ring PMID:22724069 Borealin interacts directly with the Snf7 components of ESCRT-III PMID:22724069 phosphorylates one of the three human Snf7 paralogues-CHMP4C
GO:0044878 mitotic cytokinesis checkpoint signaling	IMP PMID:24814515 ANCHR mediates Aurora-B-dependent abscission checkpoint cont...	ACCEPT	Summary: Supported core CHMP4C abscission-checkpoint annotation: mitotic cytokinesis checkpoint signaling. Reason: CHMP4C is a specialized ESCRT-III regulatory subunit for Aurora B/NoCut abscission checkpoint control, delaying abscission through phosphorylation-dependent localization and ANCHR/VPS4 retention at the midbody. Supporting Evidence: UniProt:Q96CF2 component of the cytokinesis checkpoint UniProt:Q96CF2 retains abscission-competent VPS4 PMID:22422861 CHMP4C functioned in the Aurora B-dependent abscission checkpoint PMID:22422861 depletion of CHMP4C reduced abscission time by approximately 30 minutes PMID:22422861 CHMP4C depletion circumvents the NoCut abscission checkpoint PMID:24814515 In concert with CHMP4C, ANCHR associates with VPS4 at the midbody ring PMID:24814515 abscission checkpoint is mediated by ANCHR and CHMP4C through retention of VPS4 at the midbody ring PMID:22724069 Borealin interacts directly with the Snf7 components of ESCRT-III PMID:22724069 phosphorylates one of the three human Snf7 paralogues-CHMP4C
GO:0005515 protein binding	IPI PMID:18641129 Differential requirements for Alix and ESCRT-III in cytokine...	MARK AS OVER ANNOTATED	Summary: Over-annotated CHMP4C molecular-function annotation: protein binding. Reason: The interaction evidence is real in some cases, but generic binding or homodimerization does not capture the informative CHMP4C function: ESCRT-III abscission-checkpoint regulation through Aurora B/CPC/ANCHR/VPS4-associated assemblies. Supporting Evidence: PMID:18511562 Bro1 domain of ALIX binds specifically to C-terminal residues of the human CHMP4 proteins (CHMP4A-C) PMID:36107470 CHMP4C performs a unique role in abscission checkpoint regulation file:human/CHMP4C/CHMP4C-notes.md Generic protein binding and homodimerization annotations are over-annotated.
GO:0016236 macroautophagy	TAS PMID:20588296 Membrane budding and scission by the ESCRT machinery: it's a...	KEEP AS NON CORE	Summary: Plausible PN-relevant but non-core CHMP4C autophagy/endolysosomal context: macroautophagy. Reason: The PN places CHMP4C in an ESCRT-III autophagophore closure bucket and ESCRT/MVB function supports autophagic clearance, but cached CHMP4C-specific papers do not directly test CHMP4C as the phagophore sealing effector. Supporting Evidence: PMID:17984323 Functional multivesicular bodies are required for autophagic clearance PMID:17984323 autophagic degradation is inhibited in cells depleted of ESCRT subunits file:human/CHMP4C/CHMP4C-notes.md the cached CHMP4C-specific papers do not directly assay CHMP4C as the phagophore sealing effector
GO:0000815 ESCRT III complex	TAS PMID:20588296 Membrane budding and scission by the ESCRT machinery: it's a...	ACCEPT	Summary: Supported CHMP4C ESCRT-III complex membership annotation: ESCRT III complex. Reason: CHMP4C is a Snf7-family CHMP4 subunit of ESCRT-III; its most specific cellular function is checkpoint regulation, but complex membership is sound. Supporting Evidence: UniProt:Q96CF2 Probable core component of the endosomal sorting required for transport complex III (ESCRT-III) UniProt:Q96CF2 ESCRT-III proteins mostly dissociate from the invaginating membrane before the ILV is released PMID:18511562 Bro1 domain of ALIX binds specifically to C-terminal residues of the human CHMP4 proteins (CHMP4A-C) PMID:36107470 CHMP4C performs a unique role in abscission checkpoint regulation file:human/CHMP4C/CHMP4C-notes.md CHMP4C still has bona fide ESCRT-III context.
GO:0036258 multivesicular body assembly	TAS PMID:20588296 Membrane budding and scission by the ESCRT machinery: it's a...	KEEP AS NON CORE	Summary: Plausible but non-core CHMP4C ESCRT/MVB context: multivesicular body assembly. Reason: CHMP4C belongs to the CHMP4/ESCRT-III family, but CHMP4C-specific evidence points most strongly to abscission-checkpoint regulation; MVB/endosomal sorting annotations are retained as non-core ESCRT-family context. Supporting Evidence: UniProt:Q96CF2 involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs PMID:18511562 The ESCRT pathway facilitates membrane fission events during enveloped virus budding, multivesicular body formation, and cytokinesis PMID:22422861 depletion of CHMP4B prevented MHC-I degradation, whereas depletion of CHMP4A or CHMP4C had little effect file:human/CHMP4C/CHMP4C-notes.md broad MVB cargo-degradation annotations for CHMP4C should be retained, at most, as non-core/over-annotated ESCRT-family context
GO:0039702 viral budding via host ESCRT complex	TAS PMID:20588296 Membrane budding and scission by the ESCRT machinery: it's a...	MARK AS OVER ANNOTATED	Summary: Likely paralog over-annotation for CHMP4C viral budding context: viral budding via host ESCRT complex. Reason: CHMP4C can bind ESCRT/ALIX machinery, but a direct CHMP4 paralog comparison found that CHMP4A or CHMP4C depletion did not inhibit HIV-1 release whereas CHMP4B depletion did; viral budding should not be treated as a CHMP4C core role. Supporting Evidence: PMID:22422861 depletion of CHMP4A or CHMP4C did not inhibit HIV-1 release PMID:22422861 only depletion of CHMP4B inhibited this ESCRT-dependent process file:human/CHMP4C/CHMP4C-notes.md Viral budding annotations are also likely paralog over-annotations for CHMP4C
GO:0010824 regulation of centrosome duplication	IMP PMID:20616062 Human ESCRT-III and VPS4 proteins are required for centrosom...	KEEP AS NON CORE	Summary: Plausible non-core CHMP4C centrosome/spindle/cell-cycle context: regulation of centrosome duplication. Reason: ESCRT-III/VPS4 perturbation affects centrosome and spindle maintenance, but these broad cell-cycle annotations are secondary to CHMP4C abscission-checkpoint regulation. Supporting Evidence: PMID:20616062 depletion of individual ESCRT-III and VPS4 proteins also altered centrosome and spindle pole numbers PMID:20616062 ESCRT-III/VPS4 proteins function at centrosomes to help regulate their maintenance or proliferation and then at midbodies during abscission
GO:0090611 obsolete ubiquitin-independent protein catabolic process via the multivesicular body sorting pathway	IMP PMID:22547407 ALIX binds a YPX(3)L motif of the GPCR PAR1 and mediates ubi...	MODIFY	Summary: CHMP4C annotation should be replaced with a less over-specific ESCRT/MVB term: obsolete ubiquitin-independent protein catabolic process via the multivesicular body sorting pathway. Reason: This obsolete ubiquitin-independent catabolic process term should be replaced by the non-obsolete MVB sorting pathway term. Proposed replacements: multivesicular body sorting pathway Supporting Evidence: PMID:22547407 PAR1 sorted to ILVs of MVBs through an ESCRT-III-dependent pathway independent of ubiquitination PMID:22547407 ALIX binds to a YPX3L motif of PAR1 and recruits ESCRT-III to mediate MVB/lysosomal sorting
GO:0032466 negative regulation of cytokinesis	IMP PMID:22422861 ESCRT-III governs the Aurora B-mediated abscission checkpoin...	ACCEPT	Summary: Supported core CHMP4C abscission-checkpoint annotation: negative regulation of cytokinesis. Reason: CHMP4C is a specialized ESCRT-III regulatory subunit for Aurora B/NoCut abscission checkpoint control, delaying abscission through phosphorylation-dependent localization and ANCHR/VPS4 retention at the midbody. Supporting Evidence: UniProt:Q96CF2 component of the cytokinesis checkpoint UniProt:Q96CF2 retains abscission-competent VPS4 PMID:22422861 CHMP4C functioned in the Aurora B-dependent abscission checkpoint PMID:22422861 depletion of CHMP4C reduced abscission time by approximately 30 minutes PMID:22422861 CHMP4C depletion circumvents the NoCut abscission checkpoint PMID:24814515 In concert with CHMP4C, ANCHR associates with VPS4 at the midbody ring PMID:24814515 abscission checkpoint is mediated by ANCHR and CHMP4C through retention of VPS4 at the midbody ring PMID:22724069 Borealin interacts directly with the Snf7 components of ESCRT-III PMID:22724069 phosphorylates one of the three human Snf7 paralogues-CHMP4C
GO:0032466 negative regulation of cytokinesis	IMP PMID:24814515 ANCHR mediates Aurora-B-dependent abscission checkpoint cont...	ACCEPT	Summary: Supported core CHMP4C abscission-checkpoint annotation: negative regulation of cytokinesis. Reason: CHMP4C is a specialized ESCRT-III regulatory subunit for Aurora B/NoCut abscission checkpoint control, delaying abscission through phosphorylation-dependent localization and ANCHR/VPS4 retention at the midbody. Supporting Evidence: UniProt:Q96CF2 component of the cytokinesis checkpoint UniProt:Q96CF2 retains abscission-competent VPS4 PMID:22422861 CHMP4C functioned in the Aurora B-dependent abscission checkpoint PMID:22422861 depletion of CHMP4C reduced abscission time by approximately 30 minutes PMID:22422861 CHMP4C depletion circumvents the NoCut abscission checkpoint PMID:24814515 In concert with CHMP4C, ANCHR associates with VPS4 at the midbody ring PMID:24814515 abscission checkpoint is mediated by ANCHR and CHMP4C through retention of VPS4 at the midbody ring PMID:22724069 Borealin interacts directly with the Snf7 components of ESCRT-III PMID:22724069 phosphorylates one of the three human Snf7 paralogues-CHMP4C
GO:0090543 Flemming body	IDA PMID:22422861 ESCRT-III governs the Aurora B-mediated abscission checkpoin...	ACCEPT	Summary: Supported core CHMP4C cytokinesis-checkpoint location: Flemming body. Reason: CHMP4C localizes to the midbody and Flemming body during late cytokinesis, with timing and localization tied to its Aurora B-dependent abscission-checkpoint function. Supporting Evidence: PMID:22422861 GFP-CHMP4C localized earlier to the midbody PMID:22422861 HA-CHMP4C localised to the Flemming-body in an INS-dependent manner PMID:22422861 Aurora B-dependent phosphorylation of S210 allows CHMP4C localization to the Flemming body
GO:0005515 protein binding	IPI PMID:14519844 Divergent retroviral late-budding domains recruit vacuolar p...	MARK AS OVER ANNOTATED	Summary: Over-annotated CHMP4C molecular-function annotation: protein binding. Reason: The interaction evidence is real in some cases, but generic binding or homodimerization does not capture the informative CHMP4C function: ESCRT-III abscission-checkpoint regulation through Aurora B/CPC/ANCHR/VPS4-associated assemblies. Supporting Evidence: PMID:18511562 Bro1 domain of ALIX binds specifically to C-terminal residues of the human CHMP4 proteins (CHMP4A-C) PMID:36107470 CHMP4C performs a unique role in abscission checkpoint regulation file:human/CHMP4C/CHMP4C-notes.md Generic protein binding and homodimerization annotations are over-annotated.
GO:0042803 protein homodimerization activity	IPI PMID:14519844 Divergent retroviral late-budding domains recruit vacuolar p...	MARK AS OVER ANNOTATED	Summary: Over-annotated CHMP4C molecular-function annotation: protein homodimerization activity. Reason: The interaction evidence is real in some cases, but generic binding or homodimerization does not capture the informative CHMP4C function: ESCRT-III abscission-checkpoint regulation through Aurora B/CPC/ANCHR/VPS4-associated assemblies. Supporting Evidence: PMID:18511562 Bro1 domain of ALIX binds specifically to C-terminal residues of the human CHMP4 proteins (CHMP4A-C) PMID:36107470 CHMP4C performs a unique role in abscission checkpoint regulation file:human/CHMP4C/CHMP4C-notes.md Generic protein binding and homodimerization annotations are over-annotated.
GO:0005515 protein binding	IPI PMID:14505570 The protein network of HIV budding.	MARK AS OVER ANNOTATED	Summary: Over-annotated CHMP4C molecular-function annotation: protein binding. Reason: The interaction evidence is real in some cases, but generic binding or homodimerization does not capture the informative CHMP4C function: ESCRT-III abscission-checkpoint regulation through Aurora B/CPC/ANCHR/VPS4-associated assemblies. Supporting Evidence: PMID:18511562 Bro1 domain of ALIX binds specifically to C-terminal residues of the human CHMP4 proteins (CHMP4A-C) PMID:36107470 CHMP4C performs a unique role in abscission checkpoint regulation file:human/CHMP4C/CHMP4C-notes.md Generic protein binding and homodimerization annotations are over-annotated.
GO:0042803 protein homodimerization activity	IPI PMID:14505570 The protein network of HIV budding.	MARK AS OVER ANNOTATED	Summary: Over-annotated CHMP4C molecular-function annotation: protein homodimerization activity. Reason: The interaction evidence is real in some cases, but generic binding or homodimerization does not capture the informative CHMP4C function: ESCRT-III abscission-checkpoint regulation through Aurora B/CPC/ANCHR/VPS4-associated assemblies. Supporting Evidence: PMID:18511562 Bro1 domain of ALIX binds specifically to C-terminal residues of the human CHMP4 proteins (CHMP4A-C) PMID:36107470 CHMP4C performs a unique role in abscission checkpoint regulation file:human/CHMP4C/CHMP4C-notes.md Generic protein binding and homodimerization annotations are over-annotated.
GO:0005829 cytosol	TAS Reactome:R-HSA-3159232	KEEP AS NON CORE	Summary: True or plausible broad CHMP4C location: cytosol. Reason: This location is compatible with CHMP4C cycling between cytosol and recruited ESCRT-III assemblies, but it is too broad to represent the core function by itself. Supporting Evidence: UniProt:Q96CF2 Cytoplasm. Cytosol UniProt:Q96CF2 Localizes to the midbody during late cytokinesis
GO:0005829 cytosol	TAS Reactome:R-HSA-917693	KEEP AS NON CORE	Summary: True or plausible broad CHMP4C location: cytosol. Reason: This location is compatible with CHMP4C cycling between cytosol and recruited ESCRT-III assemblies, but it is too broad to represent the core function by itself. Supporting Evidence: UniProt:Q96CF2 Cytoplasm. Cytosol UniProt:Q96CF2 Localizes to the midbody during late cytokinesis
GO:0005829 cytosol	TAS Reactome:R-HSA-917700	KEEP AS NON CORE	Summary: True or plausible broad CHMP4C location: cytosol. Reason: This location is compatible with CHMP4C cycling between cytosol and recruited ESCRT-III assemblies, but it is too broad to represent the core function by itself. Supporting Evidence: UniProt:Q96CF2 Cytoplasm. Cytosol UniProt:Q96CF2 Localizes to the midbody during late cytokinesis
GO:0005829 cytosol	TAS Reactome:R-HSA-9668389	KEEP AS NON CORE	Summary: True or plausible broad CHMP4C location: cytosol. Reason: This location is compatible with CHMP4C cycling between cytosol and recruited ESCRT-III assemblies, but it is too broad to represent the core function by itself. Supporting Evidence: UniProt:Q96CF2 Cytoplasm. Cytosol UniProt:Q96CF2 Localizes to the midbody during late cytokinesis
GO:0005829 cytosol	TAS Reactome:R-HSA-9668395	KEEP AS NON CORE	Summary: True or plausible broad CHMP4C location: cytosol. Reason: This location is compatible with CHMP4C cycling between cytosol and recruited ESCRT-III assemblies, but it is too broad to represent the core function by itself. Supporting Evidence: UniProt:Q96CF2 Cytoplasm. Cytosol UniProt:Q96CF2 Localizes to the midbody during late cytokinesis
GO:0005829 cytosol	TAS Reactome:R-HSA-9668398	KEEP AS NON CORE	Summary: True or plausible broad CHMP4C location: cytosol. Reason: This location is compatible with CHMP4C cycling between cytosol and recruited ESCRT-III assemblies, but it is too broad to represent the core function by itself. Supporting Evidence: UniProt:Q96CF2 Cytoplasm. Cytosol UniProt:Q96CF2 Localizes to the midbody during late cytokinesis
GO:0005829 cytosol	TAS Reactome:R-HSA-9668405	KEEP AS NON CORE	Summary: True or plausible broad CHMP4C location: cytosol. Reason: This location is compatible with CHMP4C cycling between cytosol and recruited ESCRT-III assemblies, but it is too broad to represent the core function by itself. Supporting Evidence: UniProt:Q96CF2 Cytoplasm. Cytosol UniProt:Q96CF2 Localizes to the midbody during late cytokinesis
GO:0005829 cytosol	TAS Reactome:R-HSA-9668415	KEEP AS NON CORE	Summary: True or plausible broad CHMP4C location: cytosol. Reason: This location is compatible with CHMP4C cycling between cytosol and recruited ESCRT-III assemblies, but it is too broad to represent the core function by itself. Supporting Evidence: UniProt:Q96CF2 Cytoplasm. Cytosol UniProt:Q96CF2 Localizes to the midbody during late cytokinesis
GO:0005829 cytosol	TAS Reactome:R-HSA-9668419	KEEP AS NON CORE	Summary: True or plausible broad CHMP4C location: cytosol. Reason: This location is compatible with CHMP4C cycling between cytosol and recruited ESCRT-III assemblies, but it is too broad to represent the core function by itself. Supporting Evidence: UniProt:Q96CF2 Cytoplasm. Cytosol UniProt:Q96CF2 Localizes to the midbody during late cytokinesis
GO:0030496 midbody	IDA PMID:22724069 The chromosomal passenger complex controls the function of e...	ACCEPT	Summary: Supported core CHMP4C cytokinesis-checkpoint location: midbody. Reason: CHMP4C localizes to the midbody and Flemming body during late cytokinesis, with timing and localization tied to its Aurora B-dependent abscission-checkpoint function. Supporting Evidence: PMID:22422861 GFP-CHMP4C localized earlier to the midbody PMID:22422861 HA-CHMP4C localised to the Flemming-body in an INS-dependent manner PMID:22422861 Aurora B-dependent phosphorylation of S210 allows CHMP4C localization to the Flemming body

📄 View Raw YAML

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

Gene Description

Existing Annotations Review

Core Functions

References

Suggested Questions for Experts

Suggested Experiments

📚 Additional Documentation

Notes

CHMP4C curation notes

2026-06-02 review

Pn Notes

CHMP4C PN Consistency Notes

Source Files Checked

Deep Research Files

AIGR Review Snapshot

PN Consistency Summary

Full Consistency Review

PN Dossier Context

PN row 1: Autophagy-Lysosome Pathway | Autophagosome closure maturation and lysosome fusion | Sealing of autophagophore membrane | ESCRT-III complex component

PN row 2: Autophagy-Lysosome Pathway | Microautophagy | General microautophagy machinery | ESCRT-III complex component

Projected GO annotations (3)

Note

📄 View Raw YAML