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.
| 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 |
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Download this section (compressed HTML)Q: Which ESCRT-III/autophagophore closure assays directly implicate CHMP4C, rather than CHMP4C being included by CHMP4-family or ESCRT-III component membership?
Q: Should GO annotations for CHMP4C distinguish checkpoint-regulatory abscission roles from CHMP4B-like execution roles in MVB cargo degradation and HIV release?
Q: Does CHMP4C phosphorylation state alter its ESCRT-III polymerization or partner recruitment in endosomal and autophagy contexts, or only at the cytokinetic midbody?
Experiment: 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.
Experiment: 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.
Experiment: 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.
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