CHMP6 encodes the human Vps20 ortholog, a myristoylated ESCRT-III component that acts at endosomal membranes as an acceptor/nucleator for ESCRT-II and helps recruit CHMP4-family ESCRT-III subunits. Its best-supported cellular role is endolysosomal membrane-cargo quality control: MVB assembly and sorting of ubiquitinated/endocytosed cargo, delivery toward lysosomal degradation, and VPS4-mediated ESCRT-III remodeling through its internal MIM2 motif. Broader ESCRT functions in viral budding, cytokinesis, nuclear-envelope sealing, plasma-membrane repair, and autophagy are biologically plausible pathway contexts, but the CHMP6-specific literature makes endosomal MVB sorting the core function.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0005635 nuclear envelope | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: Plausible secondary ESCRT pathway context for CHMP6: nuclear envelope. Reason: This annotation reflects broader ESCRT functions such as nuclear-envelope sealing, plasma membrane repair, cytokinesis, or cell-cycle phenotypes, but CHMP6-specific core evidence is stronger for endosomal MVB cargo sorting and ESCRT-III assembly/remodeling. Supporting Evidence: file:human/CHMP6/CHMP6-notes.md These processes are PN-relevant as ESCRT outputs, but they do not define CHMP6's core proteostasis function as well as endosomal cargo sorting and ESCRT-III assembly/recycling do. |
| GO:0031468 nuclear membrane reassembly | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: Plausible secondary ESCRT pathway context for CHMP6: nuclear membrane reassembly. Reason: This annotation reflects broader ESCRT functions such as nuclear-envelope sealing, plasma membrane repair, cytokinesis, or cell-cycle phenotypes, but CHMP6-specific core evidence is stronger for endosomal MVB cargo sorting and ESCRT-III assembly/remodeling. Supporting Evidence: file:human/CHMP6/CHMP6-notes.md These processes are PN-relevant as ESCRT outputs, but they do not define CHMP6's core proteostasis function as well as endosomal cargo sorting and ESCRT-III assembly/recycling do. |
| GO:0000815 ESCRT III complex | IBA GO_REF:0000033 | ACCEPT | Summary: Supported core CHMP6 ESCRT-III complex membership: ESCRT III complex. Reason: CHMP6 is the human Vps20 ESCRT-III component and serves as the ESCRT-II acceptor/nucleator for downstream ESCRT-III assembly on endosomal membranes. Supporting Evidence: PMID:15511219 interacts directly with an ESCRT-II component EAP20 and regulates endosomal cargo sorting PMID:14519844 Each of the putative ESCRT-II components Eap45, Eap30, and Eap20 bound to each other, and to the ESCRT-III protein, CHMP6 UniProt:Q96FZ7 probably serves as an acceptor for the ESCRT-II complex on endosomal membranes file:human/CHMP6/CHMP6-notes.md CHMP6 is the human Vps20 ortholog and a core ESCRT-III pathway component. |
| GO:0032511 late endosome to vacuole transport via multivesicular body sorting pathway | IBA GO_REF:0000033 | MODIFY | Summary: The MVB-sorting essence is correct, but late endosome to vacuole transport via multivesicular body sorting pathway is too broad or non-human-vacuole phrased for CHMP6. Reason: CHMP6 should be curated to the specific human endosomal MVB sorting and late endosome-to-lysosome transport terms. Proposed replacements: multivesicular body sorting pathway late endosome to lysosome transport Supporting Evidence: PMID:15511219 CHMP6 acts as an acceptor for ESCRT-II on endosomal membranes and regulates cargo sorting PMID:15511219 Ubiquitinated proteins and endocytosed EGF continuously accumulated in CHMP6-GFP-expressing cells PMID:16973552 inhibited lysosomal targeting and downregulation of the epidermal growth factor receptor PMID:18606141 The CHMP6 MIM2 Binding Site is Required for Ferroportin Degradation file:human/CHMP6/CHMP6-notes.md ESCRT-II-to-ESCRT-III handoff on endosomal membranes, MVB cargo sorting, and VPS4-coupled ESCRT-III remodeling needed for lysosomal degradation of membrane cargo |
| GO:0000776 kinetochore | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: Plausible secondary ESCRT pathway context for CHMP6: kinetochore. Reason: This annotation reflects broader ESCRT functions such as nuclear-envelope sealing, plasma membrane repair, cytokinesis, or cell-cycle phenotypes, but CHMP6-specific core evidence is stronger for endosomal MVB cargo sorting and ESCRT-III assembly/remodeling. Supporting Evidence: file:human/CHMP6/CHMP6-notes.md These processes are PN-relevant as ESCRT outputs, but they do not define CHMP6's core proteostasis function as well as endosomal cargo sorting and ESCRT-III assembly/recycling do. |
| GO:0001778 plasma membrane repair | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: Plausible secondary ESCRT pathway context for CHMP6: plasma membrane repair. Reason: This annotation reflects broader ESCRT functions such as nuclear-envelope sealing, plasma membrane repair, cytokinesis, or cell-cycle phenotypes, but CHMP6-specific core evidence is stronger for endosomal MVB cargo sorting and ESCRT-III assembly/remodeling. Supporting Evidence: file:human/CHMP6/CHMP6-notes.md These processes are PN-relevant as ESCRT outputs, but they do not define CHMP6's core proteostasis function as well as endosomal cargo sorting and ESCRT-III assembly/recycling do. |
| GO:0005643 nuclear pore | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: Plausible secondary ESCRT pathway context for CHMP6: nuclear pore. Reason: This annotation reflects broader ESCRT functions such as nuclear-envelope sealing, plasma membrane repair, cytokinesis, or cell-cycle phenotypes, but CHMP6-specific core evidence is stronger for endosomal MVB cargo sorting and ESCRT-III assembly/remodeling. Supporting Evidence: file:human/CHMP6/CHMP6-notes.md These processes are PN-relevant as ESCRT outputs, but they do not define CHMP6's core proteostasis function as well as endosomal cargo sorting and ESCRT-III assembly/recycling do. |
| GO:0005765 lysosomal membrane | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: Plausible PN-relevant but non-core ESCRT/autophagy context for CHMP6: lysosomal membrane. Reason: Autophagy and amphisome annotations reflect broader MVB/ESCRT involvement in autophagic clearance, but cached evidence does not make CHMP6-specific autophagosome maturation the core function. Supporting Evidence: PMID:17984323 Functional multivesicular bodies are required for autophagic clearance file:human/CHMP6/CHMP6-notes.md Keep nuclear envelope sealing/reassembly, nuclear pore, midbody abscission, kinetochore/microtubule, plasma membrane repair, autophagy/macroautophagy/autophagosome/amphisome/lysosomal membrane, cytosol, and extracellular exosome annotations as non-core |
| GO:0005828 kinetochore microtubule | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: Plausible secondary ESCRT pathway context for CHMP6: kinetochore microtubule. Reason: This annotation reflects broader ESCRT functions such as nuclear-envelope sealing, plasma membrane repair, cytokinesis, or cell-cycle phenotypes, but CHMP6-specific core evidence is stronger for endosomal MVB cargo sorting and ESCRT-III assembly/remodeling. Supporting Evidence: file:human/CHMP6/CHMP6-notes.md These processes are PN-relevant as ESCRT outputs, but they do not define CHMP6's core proteostasis function as well as endosomal cargo sorting and ESCRT-III assembly/recycling do. |
| GO:0007034 vacuolar transport | IEA GO_REF:0000002 | MODIFY | Summary: The MVB-sorting essence is correct, but vacuolar transport is too broad or non-human-vacuole phrased for CHMP6. Reason: CHMP6 should be curated to the specific human endosomal MVB sorting and late endosome-to-lysosome transport terms. Proposed replacements: multivesicular body sorting pathway late endosome to lysosome transport Supporting Evidence: PMID:15511219 CHMP6 acts as an acceptor for ESCRT-II on endosomal membranes and regulates cargo sorting PMID:15511219 Ubiquitinated proteins and endocytosed EGF continuously accumulated in CHMP6-GFP-expressing cells PMID:16973552 inhibited lysosomal targeting and downregulation of the epidermal growth factor receptor PMID:18606141 The CHMP6 MIM2 Binding Site is Required for Ferroportin Degradation file:human/CHMP6/CHMP6-notes.md ESCRT-II-to-ESCRT-III handoff on endosomal membranes, MVB cargo sorting, and VPS4-coupled ESCRT-III remodeling needed for lysosomal degradation of membrane cargo |
| GO:0007080 mitotic metaphase chromosome alignment | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: Plausible secondary ESCRT pathway context for CHMP6: mitotic metaphase chromosome alignment. Reason: This annotation reflects broader ESCRT functions such as nuclear-envelope sealing, plasma membrane repair, cytokinesis, or cell-cycle phenotypes, but CHMP6-specific core evidence is stronger for endosomal MVB cargo sorting and ESCRT-III assembly/remodeling. Supporting Evidence: file:human/CHMP6/CHMP6-notes.md These processes are PN-relevant as ESCRT outputs, but they do not define CHMP6's core proteostasis function as well as endosomal cargo sorting and ESCRT-III assembly/recycling do. |
| GO:0010008 endosome membrane | IEA GO_REF:0000044 | ACCEPT | Summary: Supported core CHMP6 endosomal/MVB membrane localization: endosome membrane. Reason: CHMP6 is myristoylated and localizes to endosomal/MVB membranes where it links ESCRT-II to ESCRT-III during cargo sorting. Supporting Evidence: PMID:15511219 membrane-bound CHMP6-GFP colocalized to endosome-like organelles, including MVBs PMID:15511219 CHMP6 acts as an acceptor for ESCRT-II on endosomal membranes and regulates cargo sorting file:human/CHMP6/CHMP6-notes.md Accept as core: ESCRT III complex, ESCRT III complex assembly, endosome/late endosome/MVB membrane localization |
| GO:0012505 endomembrane system | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: True but broad CHMP6 membrane location: endomembrane system. Reason: CHMP6 is a lipidated membrane-associated ESCRT-III component, but broad endomembrane/membrane terms are less informative than endosome, late-endosome, and MVB membrane localization. Supporting Evidence: PMID:15511219 CHMP6 acts as an acceptor for ESCRT-II on endosomal membranes and regulates cargo sorting file:human/CHMP6/CHMP6-notes.md Accept as core: ESCRT III complex, ESCRT III complex assembly, endosome/late endosome/MVB membrane localization |
| GO:0016020 membrane | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: True but broad CHMP6 membrane location: membrane. Reason: CHMP6 is a lipidated membrane-associated ESCRT-III component, but broad endomembrane/membrane terms are less informative than endosome, late-endosome, and MVB membrane localization. Supporting Evidence: PMID:15511219 CHMP6 acts as an acceptor for ESCRT-II on endosomal membranes and regulates cargo sorting file:human/CHMP6/CHMP6-notes.md Accept as core: ESCRT III complex, ESCRT III complex assembly, endosome/late endosome/MVB membrane localization |
| GO:0030496 midbody | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: Plausible secondary ESCRT pathway context for CHMP6: midbody. Reason: This annotation reflects broader ESCRT functions such as nuclear-envelope sealing, plasma membrane repair, cytokinesis, or cell-cycle phenotypes, but CHMP6-specific core evidence is stronger for endosomal MVB cargo sorting and ESCRT-III assembly/remodeling. Supporting Evidence: file:human/CHMP6/CHMP6-notes.md These processes are PN-relevant as ESCRT outputs, but they do not define CHMP6's core proteostasis function as well as endosomal cargo sorting and ESCRT-III assembly/recycling do. |
| GO:0031468 nuclear membrane reassembly | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: Plausible secondary ESCRT pathway context for CHMP6: nuclear membrane reassembly. Reason: This annotation reflects broader ESCRT functions such as nuclear-envelope sealing, plasma membrane repair, cytokinesis, or cell-cycle phenotypes, but CHMP6-specific core evidence is stronger for endosomal MVB cargo sorting and ESCRT-III assembly/remodeling. Supporting Evidence: file:human/CHMP6/CHMP6-notes.md These processes are PN-relevant as ESCRT outputs, but they do not define CHMP6's core proteostasis function as well as endosomal cargo sorting and ESCRT-III assembly/recycling do. |
| GO:0031902 late endosome membrane | IEA GO_REF:0000044 | ACCEPT | Summary: Supported core CHMP6 endosomal/MVB membrane localization: late endosome membrane. Reason: CHMP6 is myristoylated and localizes to endosomal/MVB membranes where it links ESCRT-II to ESCRT-III during cargo sorting. Supporting Evidence: PMID:15511219 membrane-bound CHMP6-GFP colocalized to endosome-like organelles, including MVBs PMID:15511219 CHMP6 acts as an acceptor for ESCRT-II on endosomal membranes and regulates cargo sorting file:human/CHMP6/CHMP6-notes.md Accept as core: ESCRT III complex, ESCRT III complex assembly, endosome/late endosome/MVB membrane localization |
| GO:0032585 multivesicular body membrane | IEA GO_REF:0000117 | ACCEPT | Summary: Supported core CHMP6 endosomal/MVB membrane localization: multivesicular body membrane. Reason: CHMP6 is myristoylated and localizes to endosomal/MVB membranes where it links ESCRT-II to ESCRT-III during cargo sorting. Supporting Evidence: PMID:15511219 membrane-bound CHMP6-GFP colocalized to endosome-like organelles, including MVBs PMID:15511219 CHMP6 acts as an acceptor for ESCRT-II on endosomal membranes and regulates cargo sorting file:human/CHMP6/CHMP6-notes.md Accept as core: ESCRT III complex, ESCRT III complex assembly, endosome/late endosome/MVB membrane localization |
| GO:0039702 viral budding via host ESCRT complex | IEA GO_REF:0000117 | MARK AS OVER ANNOTATED | Summary: Over-annotated CHMP6 viral-budding term: viral budding via host ESCRT complex. Reason: Viral budding is an ESCRT pathway output, but CHMP6-specific depletion did not reduce HIV-1 release/infectivity and CHMP6 overexpression was not inhibitory in a key viral budding assay. Supporting Evidence: PMID:16973552 HIV-1 release and infectivity were not reduced by efficient small interfering RNA depletion of EAP20/ESCRT-II or CHMP6/ESCRT-III PMID:18606141 Several ESCRT functions, including HIV budding, are insensitive to CHMP6 depletion PMID:14519844 nor did the ESCRT-II-binding component of ESCRT-III, CHMP6 file:human/CHMP6/CHMP6-notes.md Treat viral budding as over-annotated for CHMP6. |
| GO:0043162 ubiquitin-dependent protein catabolic process via the multivesicular body sorting pathway | IEA GO_REF:0000117 | ACCEPT | Summary: Supported core CHMP6 endolysosomal cargo-sorting process: ubiquitin-dependent protein catabolic process via the multivesicular body sorting pathway. Reason: CHMP6-specific evidence supports MVB sorting and downstream lysosomal degradation of endocytosed/ubiquitinated membrane cargo. Supporting Evidence: PMID:15511219 CHMP6 acts as an acceptor for ESCRT-II on endosomal membranes and regulates cargo sorting PMID:15511219 Ubiquitinated proteins and endocytosed EGF continuously accumulated in CHMP6-GFP-expressing cells PMID:16973552 inhibited lysosomal targeting and downregulation of the epidermal growth factor receptor PMID:18606141 The CHMP6 MIM2 Binding Site is Required for Ferroportin Degradation file:human/CHMP6/CHMP6-notes.md ESCRT-II-to-ESCRT-III handoff on endosomal membranes, MVB cargo sorting, and VPS4-coupled ESCRT-III remodeling needed for lysosomal degradation of membrane cargo |
| GO:0046761 viral budding from plasma membrane | IEA GO_REF:0000117 | MARK AS OVER ANNOTATED | Summary: Over-annotated CHMP6 viral-budding term: viral budding from plasma membrane. Reason: Viral budding is an ESCRT pathway output, but CHMP6-specific depletion did not reduce HIV-1 release/infectivity and CHMP6 overexpression was not inhibitory in a key viral budding assay. Supporting Evidence: PMID:16973552 HIV-1 release and infectivity were not reduced by efficient small interfering RNA depletion of EAP20/ESCRT-II or CHMP6/ESCRT-III PMID:18606141 Several ESCRT functions, including HIV budding, are insensitive to CHMP6 depletion PMID:14519844 nor did the ESCRT-II-binding component of ESCRT-III, CHMP6 file:human/CHMP6/CHMP6-notes.md Treat viral budding as over-annotated for CHMP6. |
| GO:0061952 midbody abscission | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: Plausible secondary ESCRT pathway context for CHMP6: midbody abscission. Reason: This annotation reflects broader ESCRT functions such as nuclear-envelope sealing, plasma membrane repair, cytokinesis, or cell-cycle phenotypes, but CHMP6-specific core evidence is stronger for endosomal MVB cargo sorting and ESCRT-III assembly/remodeling. Supporting Evidence: file:human/CHMP6/CHMP6-notes.md These processes are PN-relevant as ESCRT outputs, but they do not define CHMP6's core proteostasis function as well as endosomal cargo sorting and ESCRT-III assembly/recycling do. |
| GO:0071985 multivesicular body sorting pathway | IEA GO_REF:0000117 | ACCEPT | Summary: Supported core CHMP6 endolysosomal cargo-sorting process: multivesicular body sorting pathway. Reason: CHMP6-specific evidence supports MVB sorting and downstream lysosomal degradation of endocytosed/ubiquitinated membrane cargo. Supporting Evidence: PMID:15511219 CHMP6 acts as an acceptor for ESCRT-II on endosomal membranes and regulates cargo sorting PMID:15511219 Ubiquitinated proteins and endocytosed EGF continuously accumulated in CHMP6-GFP-expressing cells PMID:16973552 inhibited lysosomal targeting and downregulation of the epidermal growth factor receptor PMID:18606141 The CHMP6 MIM2 Binding Site is Required for Ferroportin Degradation file:human/CHMP6/CHMP6-notes.md ESCRT-II-to-ESCRT-III handoff on endosomal membranes, MVB cargo sorting, and VPS4-coupled ESCRT-III remodeling needed for lysosomal degradation of membrane cargo |
| GO:0097352 autophagosome maturation | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: Plausible PN-relevant but non-core ESCRT/autophagy context for CHMP6: autophagosome maturation. Reason: Autophagy and amphisome annotations reflect broader MVB/ESCRT involvement in autophagic clearance, but cached evidence does not make CHMP6-specific autophagosome maturation the core function. Supporting Evidence: PMID:17984323 Functional multivesicular bodies are required for autophagic clearance file:human/CHMP6/CHMP6-notes.md Keep nuclear envelope sealing/reassembly, nuclear pore, midbody abscission, kinetochore/microtubule, plasma membrane repair, autophagy/macroautophagy/autophagosome/amphisome/lysosomal membrane, cytosol, and extracellular exosome annotations as non-core |
| GO:1901673 regulation of mitotic spindle assembly | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: Plausible secondary ESCRT pathway context for CHMP6: regulation of mitotic spindle assembly. Reason: This annotation reflects broader ESCRT functions such as nuclear-envelope sealing, plasma membrane repair, cytokinesis, or cell-cycle phenotypes, but CHMP6-specific core evidence is stronger for endosomal MVB cargo sorting and ESCRT-III assembly/remodeling. Supporting Evidence: file:human/CHMP6/CHMP6-notes.md These processes are PN-relevant as ESCRT outputs, but they do not define CHMP6's core proteostasis function as well as endosomal cargo sorting and ESCRT-III assembly/recycling do. |
| GO:1902774 late endosome to lysosome transport | IEA GO_REF:0000117 | ACCEPT | Summary: Supported core CHMP6 endolysosomal cargo-sorting process: late endosome to lysosome transport. Reason: CHMP6-specific evidence supports MVB sorting and downstream lysosomal degradation of endocytosed/ubiquitinated membrane cargo. Supporting Evidence: PMID:15511219 CHMP6 acts as an acceptor for ESCRT-II on endosomal membranes and regulates cargo sorting PMID:15511219 Ubiquitinated proteins and endocytosed EGF continuously accumulated in CHMP6-GFP-expressing cells PMID:16973552 inhibited lysosomal targeting and downregulation of the epidermal growth factor receptor PMID:18606141 The CHMP6 MIM2 Binding Site is Required for Ferroportin Degradation file:human/CHMP6/CHMP6-notes.md ESCRT-II-to-ESCRT-III handoff on endosomal membranes, MVB cargo sorting, and VPS4-coupled ESCRT-III remodeling needed for lysosomal degradation of membrane cargo |
| GO:1904930 amphisome membrane | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: Plausible PN-relevant but non-core ESCRT/autophagy context for CHMP6: amphisome membrane. Reason: Autophagy and amphisome annotations reflect broader MVB/ESCRT involvement in autophagic clearance, but cached evidence does not make CHMP6-specific autophagosome maturation the core function. Supporting Evidence: PMID:17984323 Functional multivesicular bodies are required for autophagic clearance file:human/CHMP6/CHMP6-notes.md Keep nuclear envelope sealing/reassembly, nuclear pore, midbody abscission, kinetochore/microtubule, plasma membrane repair, autophagy/macroautophagy/autophagosome/amphisome/lysosomal membrane, cytosol, and extracellular exosome annotations as non-core |
| GO:0005515 protein binding | IPI PMID:16730941 A systematic analysis of human CHMP protein interactions: ad... | MARK AS OVER ANNOTATED | Summary: Generic protein binding is over-annotated for CHMP6: protein binding. Reason: The physical interactions are real, but GO:0005515 is uninformative and should be replaced by mechanistic ESCRT-II/CHMP4/VPS4 interaction context where possible. Supporting Evidence: PMID:14519844 Each of the putative ESCRT-II components Eap45, Eap30, and Eap20 bound to each other, and to the ESCRT-III protein, CHMP6 PMID:18606141 solution structure of the VPS4A MIT domain in complex with its CHMP6166-181 binding site file:human/CHMP6/CHMP6-notes.md The interactions are real, but GO:0005515 erases the meaningful ESCRT-II, CHMP4, and VPS4 context. |
| GO:0005515 protein binding | IPI PMID:16856878 CHMP7, a novel ESCRT-III-related protein, associates with CH... | MARK AS OVER ANNOTATED | Summary: Generic protein binding is over-annotated for CHMP6: protein binding. Reason: The physical interactions are real, but GO:0005515 is uninformative and should be replaced by mechanistic ESCRT-II/CHMP4/VPS4 interaction context where possible. Supporting Evidence: PMID:14519844 Each of the putative ESCRT-II components Eap45, Eap30, and Eap20 bound to each other, and to the ESCRT-III protein, CHMP6 PMID:18606141 solution structure of the VPS4A MIT domain in complex with its CHMP6166-181 binding site file:human/CHMP6/CHMP6-notes.md The interactions are real, but GO:0005515 erases the meaningful ESCRT-II, CHMP4, and VPS4 context. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | MARK AS OVER ANNOTATED | Summary: Generic protein binding is over-annotated for CHMP6: protein binding. Reason: The physical interactions are real, but GO:0005515 is uninformative and should be replaced by mechanistic ESCRT-II/CHMP4/VPS4 interaction context where possible. Supporting Evidence: PMID:14519844 Each of the putative ESCRT-II components Eap45, Eap30, and Eap20 bound to each other, and to the ESCRT-III protein, CHMP6 PMID:18606141 solution structure of the VPS4A MIT domain in complex with its CHMP6166-181 binding site file:human/CHMP6/CHMP6-notes.md The interactions are real, but GO:0005515 erases the meaningful ESCRT-II, CHMP4, and VPS4 context. |
| GO:0005515 protein binding | IPI PMID:32814053 Interactome Mapping Provides a Network of Neurodegenerative ... | MARK AS OVER ANNOTATED | Summary: Generic protein binding is over-annotated for CHMP6: protein binding. Reason: The physical interactions are real, but GO:0005515 is uninformative and should be replaced by mechanistic ESCRT-II/CHMP4/VPS4 interaction context where possible. Supporting Evidence: PMID:14519844 Each of the putative ESCRT-II components Eap45, Eap30, and Eap20 bound to each other, and to the ESCRT-III protein, CHMP6 PMID:18606141 solution structure of the VPS4A MIT domain in complex with its CHMP6166-181 binding site file:human/CHMP6/CHMP6-notes.md The interactions are real, but GO:0005515 erases the meaningful ESCRT-II, CHMP4, and VPS4 context. |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | MARK AS OVER ANNOTATED | Summary: Generic protein binding is over-annotated for CHMP6: protein binding. Reason: The physical interactions are real, but GO:0005515 is uninformative and should be replaced by mechanistic ESCRT-II/CHMP4/VPS4 interaction context where possible. Supporting Evidence: PMID:14519844 Each of the putative ESCRT-II components Eap45, Eap30, and Eap20 bound to each other, and to the ESCRT-III protein, CHMP6 PMID:18606141 solution structure of the VPS4A MIT domain in complex with its CHMP6166-181 binding site file:human/CHMP6/CHMP6-notes.md The interactions are real, but GO:0005515 erases the meaningful ESCRT-II, CHMP4, and VPS4 context. |
| 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 ESCRT/autophagy context for CHMP6: autophagosome membrane. Reason: Autophagy and amphisome annotations reflect broader MVB/ESCRT involvement in autophagic clearance, but cached evidence does not make CHMP6-specific autophagosome maturation the core function. Supporting Evidence: PMID:17984323 Functional multivesicular bodies are required for autophagic clearance file:human/CHMP6/CHMP6-notes.md Keep nuclear envelope sealing/reassembly, nuclear pore, midbody abscission, kinetochore/microtubule, plasma membrane repair, autophagy/macroautophagy/autophagosome/amphisome/lysosomal membrane, cytosol, and extracellular exosome annotations as non-core |
| GO:0000776 kinetochore | IDA PMID:26040712 Spastin and ESCRT-III coordinate mitotic spindle disassembly... | KEEP AS NON CORE | Summary: Plausible secondary ESCRT pathway context for CHMP6: kinetochore. Reason: This annotation reflects broader ESCRT functions such as nuclear-envelope sealing, plasma membrane repair, cytokinesis, or cell-cycle phenotypes, but CHMP6-specific core evidence is stronger for endosomal MVB cargo sorting and ESCRT-III assembly/remodeling. Supporting Evidence: file:human/CHMP6/CHMP6-notes.md These processes are PN-relevant as ESCRT outputs, but they do not define CHMP6's core proteostasis function as well as endosomal cargo sorting and ESCRT-III assembly/recycling do. |
| GO:0000815 ESCRT III complex | NAS PMID:36107470 Comprehensive analysis of the human ESCRT-III-MIT domain int... | ACCEPT | Summary: Supported core CHMP6 ESCRT-III complex membership: ESCRT III complex. Reason: CHMP6 is the human Vps20 ESCRT-III component and serves as the ESCRT-II acceptor/nucleator for downstream ESCRT-III assembly on endosomal membranes. Supporting Evidence: PMID:15511219 interacts directly with an ESCRT-II component EAP20 and regulates endosomal cargo sorting PMID:14519844 Each of the putative ESCRT-II components Eap45, Eap30, and Eap20 bound to each other, and to the ESCRT-III protein, CHMP6 UniProt:Q96FZ7 probably serves as an acceptor for the ESCRT-II complex on endosomal membranes file:human/CHMP6/CHMP6-notes.md CHMP6 is the human Vps20 ortholog and a core ESCRT-III pathway component. |
| GO:0001778 plasma membrane repair | IDA PMID:24482116 ESCRT machinery is required for plasma membrane repair. | KEEP AS NON CORE | Summary: Plausible secondary ESCRT pathway context for CHMP6: plasma membrane repair. Reason: This annotation reflects broader ESCRT functions such as nuclear-envelope sealing, plasma membrane repair, cytokinesis, or cell-cycle phenotypes, but CHMP6-specific core evidence is stronger for endosomal MVB cargo sorting and ESCRT-III assembly/remodeling. Supporting Evidence: file:human/CHMP6/CHMP6-notes.md These processes are PN-relevant as ESCRT outputs, but they do not define CHMP6's core proteostasis function as well as endosomal cargo sorting and ESCRT-III assembly/recycling do. |
| GO:0005643 nuclear pore | IDA PMID:26040713 ESCRT-III controls nuclear envelope reformation. | KEEP AS NON CORE | Summary: Plausible secondary ESCRT pathway context for CHMP6: nuclear pore. Reason: This annotation reflects broader ESCRT functions such as nuclear-envelope sealing, plasma membrane repair, cytokinesis, or cell-cycle phenotypes, but CHMP6-specific core evidence is stronger for endosomal MVB cargo sorting and ESCRT-III assembly/remodeling. Supporting Evidence: file:human/CHMP6/CHMP6-notes.md These processes are PN-relevant as ESCRT outputs, but they do not define CHMP6's core proteostasis function as well as endosomal cargo sorting and ESCRT-III assembly/recycling do. |
| 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 ESCRT/autophagy context for CHMP6: lysosomal membrane. Reason: Autophagy and amphisome annotations reflect broader MVB/ESCRT involvement in autophagic clearance, but cached evidence does not make CHMP6-specific autophagosome maturation the core function. Supporting Evidence: PMID:17984323 Functional multivesicular bodies are required for autophagic clearance file:human/CHMP6/CHMP6-notes.md Keep nuclear envelope sealing/reassembly, nuclear pore, midbody abscission, kinetochore/microtubule, plasma membrane repair, autophagy/macroautophagy/autophagosome/amphisome/lysosomal membrane, cytosol, and extracellular exosome annotations as non-core |
| GO:0005828 kinetochore microtubule | IDA PMID:26040712 Spastin and ESCRT-III coordinate mitotic spindle disassembly... | KEEP AS NON CORE | Summary: Plausible secondary ESCRT pathway context for CHMP6: kinetochore microtubule. Reason: This annotation reflects broader ESCRT functions such as nuclear-envelope sealing, plasma membrane repair, cytokinesis, or cell-cycle phenotypes, but CHMP6-specific core evidence is stronger for endosomal MVB cargo sorting and ESCRT-III assembly/remodeling. Supporting Evidence: file:human/CHMP6/CHMP6-notes.md These processes are PN-relevant as ESCRT outputs, but they do not define CHMP6's core proteostasis function as well as endosomal cargo sorting and ESCRT-III assembly/recycling do. |
| GO:0005886 plasma membrane | IDA PMID:24878737 Structure of cellular ESCRT-III spirals and their relationsh... | KEEP AS NON CORE | Summary: Plausible secondary ESCRT pathway context for CHMP6: plasma membrane. Reason: This annotation reflects broader ESCRT functions such as nuclear-envelope sealing, plasma membrane repair, cytokinesis, or cell-cycle phenotypes, but CHMP6-specific core evidence is stronger for endosomal MVB cargo sorting and ESCRT-III assembly/remodeling. Supporting Evidence: file:human/CHMP6/CHMP6-notes.md These processes are PN-relevant as ESCRT outputs, but they do not define CHMP6's core proteostasis function as well as endosomal cargo sorting and ESCRT-III assembly/recycling do. |
| GO:0006914 autophagy | IMP PMID:17984323 Functional multivesicular bodies are required for autophagic... | KEEP AS NON CORE | Summary: Plausible PN-relevant but non-core ESCRT/autophagy context for CHMP6: autophagy. Reason: Autophagy and amphisome annotations reflect broader MVB/ESCRT involvement in autophagic clearance, but cached evidence does not make CHMP6-specific autophagosome maturation the core function. Supporting Evidence: PMID:17984323 Functional multivesicular bodies are required for autophagic clearance file:human/CHMP6/CHMP6-notes.md Keep nuclear envelope sealing/reassembly, nuclear pore, midbody abscission, kinetochore/microtubule, plasma membrane repair, autophagy/macroautophagy/autophagosome/amphisome/lysosomal membrane, cytosol, and extracellular exosome annotations as non-core |
| GO:0006997 nucleus organization | IMP PMID:20616062 Human ESCRT-III and VPS4 proteins are required for centrosom... | KEEP AS NON CORE | Summary: Plausible secondary ESCRT pathway context for CHMP6: nucleus organization. Reason: This annotation reflects broader ESCRT functions such as nuclear-envelope sealing, plasma membrane repair, cytokinesis, or cell-cycle phenotypes, but CHMP6-specific core evidence is stronger for endosomal MVB cargo sorting and ESCRT-III assembly/remodeling. Supporting Evidence: file:human/CHMP6/CHMP6-notes.md These processes are PN-relevant as ESCRT outputs, but they do not define CHMP6's core proteostasis function as well as endosomal cargo sorting and ESCRT-III assembly/recycling do. |
| 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 secondary ESCRT pathway context for CHMP6: mitotic metaphase chromosome alignment. Reason: This annotation reflects broader ESCRT functions such as nuclear-envelope sealing, plasma membrane repair, cytokinesis, or cell-cycle phenotypes, but CHMP6-specific core evidence is stronger for endosomal MVB cargo sorting and ESCRT-III assembly/remodeling. Supporting Evidence: file:human/CHMP6/CHMP6-notes.md These processes are PN-relevant as ESCRT outputs, but they do not define CHMP6's core proteostasis function as well as endosomal cargo sorting and ESCRT-III assembly/recycling do. |
| GO:0030496 midbody | IDA PMID:26040712 Spastin and ESCRT-III coordinate mitotic spindle disassembly... | KEEP AS NON CORE | Summary: Plausible secondary ESCRT pathway context for CHMP6: midbody. Reason: This annotation reflects broader ESCRT functions such as nuclear-envelope sealing, plasma membrane repair, cytokinesis, or cell-cycle phenotypes, but CHMP6-specific core evidence is stronger for endosomal MVB cargo sorting and ESCRT-III assembly/remodeling. Supporting Evidence: file:human/CHMP6/CHMP6-notes.md These processes are PN-relevant as ESCRT outputs, but they do not define CHMP6's core proteostasis function as well as endosomal cargo sorting and ESCRT-III assembly/recycling do. |
| GO:0031468 nuclear membrane reassembly | IMP PMID:26040713 ESCRT-III controls nuclear envelope reformation. | KEEP AS NON CORE | Summary: Plausible secondary ESCRT pathway context for CHMP6: nuclear membrane reassembly. Reason: This annotation reflects broader ESCRT functions such as nuclear-envelope sealing, plasma membrane repair, cytokinesis, or cell-cycle phenotypes, but CHMP6-specific core evidence is stronger for endosomal MVB cargo sorting and ESCRT-III assembly/remodeling. Supporting Evidence: file:human/CHMP6/CHMP6-notes.md These processes are PN-relevant as ESCRT outputs, but they do not define CHMP6's core proteostasis function as well as endosomal cargo sorting and ESCRT-III assembly/recycling do. |
| GO:0032585 multivesicular body membrane | IDA PMID:16554368 The ESCRT-III subunit hVps24 is required for degradation but... | ACCEPT | Summary: Supported core CHMP6 endosomal/MVB membrane localization: multivesicular body membrane. Reason: CHMP6 is myristoylated and localizes to endosomal/MVB membranes where it links ESCRT-II to ESCRT-III during cargo sorting. Supporting Evidence: PMID:15511219 membrane-bound CHMP6-GFP colocalized to endosome-like organelles, including MVBs PMID:15511219 CHMP6 acts as an acceptor for ESCRT-II on endosomal membranes and regulates cargo sorting file:human/CHMP6/CHMP6-notes.md Accept as core: ESCRT III complex, ESCRT III complex assembly, endosome/late endosome/MVB membrane localization |
| GO:0036258 multivesicular body assembly | NAS PMID:16505166 Recycling of ESCRTs by the AAA-ATPase Vps4 is regulated by a... | ACCEPT | Summary: Supported core CHMP6 endolysosomal cargo-sorting process: multivesicular body assembly. Reason: CHMP6-specific evidence supports MVB sorting and downstream lysosomal degradation of endocytosed/ubiquitinated membrane cargo. Supporting Evidence: PMID:15511219 CHMP6 acts as an acceptor for ESCRT-II on endosomal membranes and regulates cargo sorting PMID:15511219 Ubiquitinated proteins and endocytosed EGF continuously accumulated in CHMP6-GFP-expressing cells PMID:16973552 inhibited lysosomal targeting and downregulation of the epidermal growth factor receptor PMID:18606141 The CHMP6 MIM2 Binding Site is Required for Ferroportin Degradation file:human/CHMP6/CHMP6-notes.md ESCRT-II-to-ESCRT-III handoff on endosomal membranes, MVB cargo sorting, and VPS4-coupled ESCRT-III remodeling needed for lysosomal degradation of membrane cargo |
| 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: Over-annotated CHMP6 viral-budding term: viral budding via host ESCRT complex. Reason: Viral budding is an ESCRT pathway output, but CHMP6-specific depletion did not reduce HIV-1 release/infectivity and CHMP6 overexpression was not inhibitory in a key viral budding assay. Supporting Evidence: PMID:16973552 HIV-1 release and infectivity were not reduced by efficient small interfering RNA depletion of EAP20/ESCRT-II or CHMP6/ESCRT-III PMID:18606141 Several ESCRT functions, including HIV budding, are insensitive to CHMP6 depletion PMID:14519844 nor did the ESCRT-II-binding component of ESCRT-III, CHMP6 file:human/CHMP6/CHMP6-notes.md Treat viral budding as over-annotated for CHMP6. |
| GO:0043162 ubiquitin-dependent protein catabolic process via the multivesicular body sorting pathway | IDA PMID:17984323 Functional multivesicular bodies are required for autophagic... | ACCEPT | Summary: Supported core CHMP6 endolysosomal cargo-sorting process: ubiquitin-dependent protein catabolic process via the multivesicular body sorting pathway. Reason: CHMP6-specific evidence supports MVB sorting and downstream lysosomal degradation of endocytosed/ubiquitinated membrane cargo. Supporting Evidence: PMID:15511219 CHMP6 acts as an acceptor for ESCRT-II on endosomal membranes and regulates cargo sorting PMID:15511219 Ubiquitinated proteins and endocytosed EGF continuously accumulated in CHMP6-GFP-expressing cells PMID:16973552 inhibited lysosomal targeting and downregulation of the epidermal growth factor receptor PMID:18606141 The CHMP6 MIM2 Binding Site is Required for Ferroportin Degradation file:human/CHMP6/CHMP6-notes.md ESCRT-II-to-ESCRT-III handoff on endosomal membranes, MVB cargo sorting, and VPS4-coupled ESCRT-III remodeling needed for lysosomal degradation of membrane cargo |
| GO:0046761 viral budding from plasma membrane | IDA PMID:24878737 Structure of cellular ESCRT-III spirals and their relationsh... | MARK AS OVER ANNOTATED | Summary: Over-annotated CHMP6 viral-budding term: viral budding from plasma membrane. Reason: Viral budding is an ESCRT pathway output, but CHMP6-specific depletion did not reduce HIV-1 release/infectivity and CHMP6 overexpression was not inhibitory in a key viral budding assay. Supporting Evidence: PMID:16973552 HIV-1 release and infectivity were not reduced by efficient small interfering RNA depletion of EAP20/ESCRT-II or CHMP6/ESCRT-III PMID:18606141 Several ESCRT functions, including HIV budding, are insensitive to CHMP6 depletion PMID:14519844 nor did the ESCRT-II-binding component of ESCRT-III, CHMP6 file:human/CHMP6/CHMP6-notes.md Treat viral budding as over-annotated for CHMP6. |
| GO:0051469 vesicle fusion with vacuole | NAS PMID:16505166 Recycling of ESCRTs by the AAA-ATPase Vps4 is regulated by a... | MODIFY | Summary: This transport/fusion annotation should be replaced with the better-supported CHMP6 endolysosomal cargo-sorting route: vesicle fusion with vacuole. Reason: The evidence supports MVB sorting and delivery toward lysosomal degradation, not a CHMP6-specific vesicle-fusion activity. Proposed replacements: late endosome to lysosome transport Supporting Evidence: PMID:15511219 CHMP6 acts as an acceptor for ESCRT-II on endosomal membranes and regulates cargo sorting PMID:15511219 Ubiquitinated proteins and endocytosed EGF continuously accumulated in CHMP6-GFP-expressing cells PMID:16973552 inhibited lysosomal targeting and downregulation of the epidermal growth factor receptor PMID:18606141 The CHMP6 MIM2 Binding Site is Required for Ferroportin Degradation file:human/CHMP6/CHMP6-notes.md ESCRT-II-to-ESCRT-III handoff on endosomal membranes, MVB cargo sorting, and VPS4-coupled ESCRT-III remodeling needed for lysosomal degradation of membrane cargo |
| GO:0061763 multivesicular body-lysosome fusion | NAS PMID:16505166 Recycling of ESCRTs by the AAA-ATPase Vps4 is regulated by a... | MODIFY | Summary: This transport/fusion annotation should be replaced with the better-supported CHMP6 endolysosomal cargo-sorting route: multivesicular body-lysosome fusion. Reason: The evidence supports MVB sorting and delivery toward lysosomal degradation, not a CHMP6-specific vesicle-fusion activity. Proposed replacements: late endosome to lysosome transport Supporting Evidence: PMID:15511219 CHMP6 acts as an acceptor for ESCRT-II on endosomal membranes and regulates cargo sorting PMID:15511219 Ubiquitinated proteins and endocytosed EGF continuously accumulated in CHMP6-GFP-expressing cells PMID:16973552 inhibited lysosomal targeting and downregulation of the epidermal growth factor receptor PMID:18606141 The CHMP6 MIM2 Binding Site is Required for Ferroportin Degradation file:human/CHMP6/CHMP6-notes.md ESCRT-II-to-ESCRT-III handoff on endosomal membranes, MVB cargo sorting, and VPS4-coupled ESCRT-III remodeling needed for lysosomal degradation of membrane cargo |
| GO:0061952 midbody abscission | IMP PMID:20616062 Human ESCRT-III and VPS4 proteins are required for centrosom... | KEEP AS NON CORE | Summary: Plausible secondary ESCRT pathway context for CHMP6: midbody abscission. Reason: This annotation reflects broader ESCRT functions such as nuclear-envelope sealing, plasma membrane repair, cytokinesis, or cell-cycle phenotypes, but CHMP6-specific core evidence is stronger for endosomal MVB cargo sorting and ESCRT-III assembly/remodeling. Supporting Evidence: file:human/CHMP6/CHMP6-notes.md These processes are PN-relevant as ESCRT outputs, but they do not define CHMP6's core proteostasis function as well as endosomal cargo sorting and ESCRT-III assembly/recycling do. |
| GO:0071985 multivesicular body sorting pathway | IDA PMID:16554368 The ESCRT-III subunit hVps24 is required for degradation but... | ACCEPT | Summary: Supported core CHMP6 endolysosomal cargo-sorting process: multivesicular body sorting pathway. Reason: CHMP6-specific evidence supports MVB sorting and downstream lysosomal degradation of endocytosed/ubiquitinated membrane cargo. Supporting Evidence: PMID:15511219 CHMP6 acts as an acceptor for ESCRT-II on endosomal membranes and regulates cargo sorting PMID:15511219 Ubiquitinated proteins and endocytosed EGF continuously accumulated in CHMP6-GFP-expressing cells PMID:16973552 inhibited lysosomal targeting and downregulation of the epidermal growth factor receptor PMID:18606141 The CHMP6 MIM2 Binding Site is Required for Ferroportin Degradation file:human/CHMP6/CHMP6-notes.md ESCRT-II-to-ESCRT-III handoff on endosomal membranes, MVB cargo sorting, and VPS4-coupled ESCRT-III remodeling needed for lysosomal degradation of membrane cargo |
| GO:0090148 membrane fission | NAS PMID:19234443 Membrane scission by the ESCRT-III complex. | ACCEPT | Summary: Supported pathway-level ESCRT-III membrane-fission output for CHMP6: membrane fission. Reason: Membrane fission is a core output of ESCRT-III assemblies; CHMP6 contributes as the ESCRT-II acceptor and VPS4-recognized MIM2-bearing ESCRT-III component. Supporting Evidence: PMID:18606141 VPS4 and ESCRT-III might work together to produce the constriction necessary for vesicle extrusion and/or membrane fission PMID:17547705 removing approximately 40 amino acids from the C-terminus of each protein unmasks a common ability to associate with endosomal membranes and assemble into large polymeric complexes file:human/CHMP6/CHMP6-notes.md ESCRT-II-to-ESCRT-III handoff on endosomal membranes, MVB cargo sorting, and VPS4-coupled ESCRT-III remodeling needed for lysosomal degradation of membrane cargo |
| 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 ESCRT/autophagy context for CHMP6: autophagosome maturation. Reason: Autophagy and amphisome annotations reflect broader MVB/ESCRT involvement in autophagic clearance, but cached evidence does not make CHMP6-specific autophagosome maturation the core function. Supporting Evidence: PMID:17984323 Functional multivesicular bodies are required for autophagic clearance file:human/CHMP6/CHMP6-notes.md Keep nuclear envelope sealing/reassembly, nuclear pore, midbody abscission, kinetochore/microtubule, plasma membrane repair, autophagy/macroautophagy/autophagosome/amphisome/lysosomal membrane, cytosol, and extracellular exosome annotations as non-core |
| 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 secondary ESCRT pathway context for CHMP6: regulation of mitotic spindle assembly. Reason: This annotation reflects broader ESCRT functions such as nuclear-envelope sealing, plasma membrane repair, cytokinesis, or cell-cycle phenotypes, but CHMP6-specific core evidence is stronger for endosomal MVB cargo sorting and ESCRT-III assembly/remodeling. Supporting Evidence: file:human/CHMP6/CHMP6-notes.md These processes are PN-relevant as ESCRT outputs, but they do not define CHMP6's core proteostasis function as well as endosomal cargo sorting and ESCRT-III assembly/recycling do. |
| GO:1902774 late endosome to lysosome transport | IMP PMID:17984323 Functional multivesicular bodies are required for autophagic... | ACCEPT | Summary: Supported core CHMP6 endolysosomal cargo-sorting process: late endosome to lysosome transport. Reason: CHMP6-specific evidence supports MVB sorting and downstream lysosomal degradation of endocytosed/ubiquitinated membrane cargo. Supporting Evidence: PMID:15511219 CHMP6 acts as an acceptor for ESCRT-II on endosomal membranes and regulates cargo sorting PMID:15511219 Ubiquitinated proteins and endocytosed EGF continuously accumulated in CHMP6-GFP-expressing cells PMID:16973552 inhibited lysosomal targeting and downregulation of the epidermal growth factor receptor PMID:18606141 The CHMP6 MIM2 Binding Site is Required for Ferroportin Degradation file:human/CHMP6/CHMP6-notes.md ESCRT-II-to-ESCRT-III handoff on endosomal membranes, MVB cargo sorting, and VPS4-coupled ESCRT-III remodeling needed for lysosomal degradation of membrane cargo |
| 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 ESCRT/autophagy context for CHMP6: amphisome membrane. Reason: Autophagy and amphisome annotations reflect broader MVB/ESCRT involvement in autophagic clearance, but cached evidence does not make CHMP6-specific autophagosome maturation the core function. Supporting Evidence: PMID:17984323 Functional multivesicular bodies are required for autophagic clearance file:human/CHMP6/CHMP6-notes.md Keep nuclear envelope sealing/reassembly, nuclear pore, midbody abscission, kinetochore/microtubule, plasma membrane repair, autophagy/macroautophagy/autophagosome/amphisome/lysosomal membrane, cytosol, and extracellular exosome annotations as non-core |
| GO:0042176 regulation of protein catabolic process | IMP PMID:18606141 Two distinct modes of ESCRT-III recognition are required for... | MODIFY | Summary: The protein-catabolism concept is correct but should be made CHMP6-specific: regulation of protein catabolic process. Reason: Ferroportin and EGFR evidence supports ubiquitin-dependent MVB cargo sorting and late endosome-to-lysosome delivery, not general regulation of protein catabolism. Proposed replacements: ubiquitin-dependent protein catabolic process via the multivesicular body sorting pathway late endosome to lysosome transport Supporting Evidence: PMID:15511219 CHMP6 acts as an acceptor for ESCRT-II on endosomal membranes and regulates cargo sorting PMID:15511219 Ubiquitinated proteins and endocytosed EGF continuously accumulated in CHMP6-GFP-expressing cells PMID:16973552 inhibited lysosomal targeting and downregulation of the epidermal growth factor receptor PMID:18606141 The CHMP6 MIM2 Binding Site is Required for Ferroportin Degradation file:human/CHMP6/CHMP6-notes.md ESCRT-II-to-ESCRT-III handoff on endosomal membranes, MVB cargo sorting, and VPS4-coupled ESCRT-III remodeling needed for lysosomal degradation of membrane cargo |
| GO:0007175 negative regulation of epidermal growth factor-activated receptor activity | IMP PMID:16973552 Human ESCRT-II complex and its role in human immunodeficienc... | ACCEPT | Summary: Supported cargo-specific consequence of CHMP6 MVB sorting: negative regulation of epidermal growth factor-activated receptor activity. Reason: CHMP6 depletion impairs EGFR lysosomal targeting/downregulation, making this a supported readout of CHMP6-dependent endosomal cargo sorting rather than an independent signaling activity. Supporting Evidence: PMID:16973552 inhibited lysosomal targeting and downregulation of the epidermal growth factor receptor PMID:15511219 endocytosed EGF continuously accumulated in CHMP6-GFP-expressing cells file:human/CHMP6/CHMP6-notes.md ESCRT-II-to-ESCRT-III handoff on endosomal membranes, MVB cargo sorting, and VPS4-coupled ESCRT-III remodeling needed for lysosomal degradation of membrane cargo |
| GO:0044877 protein-containing complex binding | IDA PMID:16973552 Human ESCRT-II complex and its role in human immunodeficienc... | ACCEPT | Summary: Supported CHMP6 ESCRT protein-complex binding mechanism: protein-containing complex binding. Reason: Although broad, this molecular-function term captures the direct ESCRT-II/ESCRT-III/VPS4 binding mechanism that positions CHMP6 at the ESCRT-II-to-ESCRT-III handoff. Supporting Evidence: PMID:15511219 Interactions of CHMP6 with another ESCRT-III component CHMP4b/Shax PMID:16973552 EAP20 bound the N-terminal half of CHMP6/ESCRT-III PMID:18606141 solution structure of the VPS4A MIT domain in complex with its CHMP6166-181 binding site file:human/CHMP6/CHMP6-notes.md protein-containing complex binding where it reflects ESCRT-II/ESCRT-III handoff rather than generic binding |
| 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 ESCRT/autophagy context for CHMP6: macroautophagy. Reason: Autophagy and amphisome annotations reflect broader MVB/ESCRT involvement in autophagic clearance, but cached evidence does not make CHMP6-specific autophagosome maturation the core function. Supporting Evidence: PMID:17984323 Functional multivesicular bodies are required for autophagic clearance file:human/CHMP6/CHMP6-notes.md Keep nuclear envelope sealing/reassembly, nuclear pore, midbody abscission, kinetochore/microtubule, plasma membrane repair, autophagy/macroautophagy/autophagosome/amphisome/lysosomal membrane, cytosol, and extracellular exosome annotations as non-core |
| GO:0000815 ESCRT III complex | TAS PMID:20588296 Membrane budding and scission by the ESCRT machinery: it's a... | ACCEPT | Summary: Supported core CHMP6 ESCRT-III complex membership: ESCRT III complex. Reason: CHMP6 is the human Vps20 ESCRT-III component and serves as the ESCRT-II acceptor/nucleator for downstream ESCRT-III assembly on endosomal membranes. Supporting Evidence: PMID:15511219 interacts directly with an ESCRT-II component EAP20 and regulates endosomal cargo sorting PMID:14519844 Each of the putative ESCRT-II components Eap45, Eap30, and Eap20 bound to each other, and to the ESCRT-III protein, CHMP6 UniProt:Q96FZ7 probably serves as an acceptor for the ESCRT-II complex on endosomal membranes file:human/CHMP6/CHMP6-notes.md CHMP6 is the human Vps20 ortholog and a core ESCRT-III pathway component. |
| GO:0036258 multivesicular body assembly | TAS PMID:20588296 Membrane budding and scission by the ESCRT machinery: it's a... | ACCEPT | Summary: Supported core CHMP6 endolysosomal cargo-sorting process: multivesicular body assembly. Reason: CHMP6-specific evidence supports MVB sorting and downstream lysosomal degradation of endocytosed/ubiquitinated membrane cargo. Supporting Evidence: PMID:15511219 CHMP6 acts as an acceptor for ESCRT-II on endosomal membranes and regulates cargo sorting PMID:15511219 Ubiquitinated proteins and endocytosed EGF continuously accumulated in CHMP6-GFP-expressing cells PMID:16973552 inhibited lysosomal targeting and downregulation of the epidermal growth factor receptor PMID:18606141 The CHMP6 MIM2 Binding Site is Required for Ferroportin Degradation file:human/CHMP6/CHMP6-notes.md ESCRT-II-to-ESCRT-III handoff on endosomal membranes, MVB cargo sorting, and VPS4-coupled ESCRT-III remodeling needed for lysosomal degradation of membrane cargo |
| GO:1904902 ESCRT III complex assembly | NAS PMID:20588296 Membrane budding and scission by the ESCRT machinery: it's a... | ACCEPT | Summary: Supported core CHMP6 role in ESCRT-III assembly/remodeling: ESCRT III complex assembly. Reason: As the Vps20 ortholog, CHMP6 accepts ESCRT-II and recruits/interacts with CHMP4-family ESCRT-III subunits; VPS4-MIM2 binding then supports ESCRT-III remodeling. Supporting Evidence: PMID:15511219 interactions between CHMP6 and CHMP4b as well as between CHMP6 and EAP20 PMID:17547705 removing approximately 40 amino acids from the C-terminus of each protein unmasks a common ability to associate with endosomal membranes and assemble into large polymeric complexes PMID:18606141 both MIM1 and MIM2 interactions contribute in recruiting VPS4A to endosomal membranes file:human/CHMP6/CHMP6-notes.md CHMP6 has a conserved ESCRT-III autoinhibited/open behavior. |
| GO:0005515 protein binding | IPI PMID:16973552 Human ESCRT-II complex and its role in human immunodeficienc... | MARK AS OVER ANNOTATED | Summary: Generic protein binding is over-annotated for CHMP6: protein binding. Reason: The physical interactions are real, but GO:0005515 is uninformative and should be replaced by mechanistic ESCRT-II/CHMP4/VPS4 interaction context where possible. Supporting Evidence: PMID:14519844 Each of the putative ESCRT-II components Eap45, Eap30, and Eap20 bound to each other, and to the ESCRT-III protein, CHMP6 PMID:18606141 solution structure of the VPS4A MIT domain in complex with its CHMP6166-181 binding site file:human/CHMP6/CHMP6-notes.md The interactions are real, but GO:0005515 erases the meaningful ESCRT-II, CHMP4, and VPS4 context. |
| GO:0010008 endosome membrane | IDA PMID:16973552 Human ESCRT-II complex and its role in human immunodeficienc... | ACCEPT | Summary: Supported core CHMP6 endosomal/MVB membrane localization: endosome membrane. Reason: CHMP6 is myristoylated and localizes to endosomal/MVB membranes where it links ESCRT-II to ESCRT-III during cargo sorting. Supporting Evidence: PMID:15511219 membrane-bound CHMP6-GFP colocalized to endosome-like organelles, including MVBs PMID:15511219 CHMP6 acts as an acceptor for ESCRT-II on endosomal membranes and regulates cargo sorting file:human/CHMP6/CHMP6-notes.md Accept as core: ESCRT III complex, ESCRT III complex assembly, endosome/late endosome/MVB membrane localization |
| GO:0000815 ESCRT III complex | IDA PMID:24878737 Structure of cellular ESCRT-III spirals and their relationsh... | ACCEPT | Summary: Supported core CHMP6 ESCRT-III complex membership: ESCRT III complex. Reason: CHMP6 is the human Vps20 ESCRT-III component and serves as the ESCRT-II acceptor/nucleator for downstream ESCRT-III assembly on endosomal membranes. Supporting Evidence: PMID:15511219 interacts directly with an ESCRT-II component EAP20 and regulates endosomal cargo sorting PMID:14519844 Each of the putative ESCRT-II components Eap45, Eap30, and Eap20 bound to each other, and to the ESCRT-III protein, CHMP6 UniProt:Q96FZ7 probably serves as an acceptor for the ESCRT-II complex on endosomal membranes file:human/CHMP6/CHMP6-notes.md CHMP6 is the human Vps20 ortholog and a core ESCRT-III pathway component. |
| GO:1903541 regulation of exosomal secretion | IMP NOT PMID:22660413 Syndecan-syntenin-ALIX regulates the biogenesis of exosomes. | ACCEPT | Summary: Retain the existing NOT annotation for exosome secretion. Reason: The GOA assertion is explicitly negated; the review should not convert this into a positive CHMP6 exosome-secretion function. Supporting Evidence: PMID:22660413 Syndecan-syntenin-ALIX regulates the biogenesis of exosomes file:human/CHMP6/CHMP6-notes.md The negated exosome secretion annotation should be retained as a supported NOT annotation rather than converted into a positive functional claim |
| GO:0016020 membrane | HDA PMID:19946888 Defining the membrane proteome of NK cells. | KEEP AS NON CORE | Summary: True but broad CHMP6 membrane location: membrane. Reason: CHMP6 is a lipidated membrane-associated ESCRT-III component, but broad endomembrane/membrane terms are less informative than endosome, late-endosome, and MVB membrane localization. Supporting Evidence: PMID:15511219 CHMP6 acts as an acceptor for ESCRT-II on endosomal membranes and regulates cargo sorting file:human/CHMP6/CHMP6-notes.md Accept as core: ESCRT III complex, ESCRT III complex assembly, endosome/late endosome/MVB membrane localization |
| GO:0005515 protein binding | IPI PMID:14519844 Divergent retroviral late-budding domains recruit vacuolar p... | MARK AS OVER ANNOTATED | Summary: Generic protein binding is over-annotated for CHMP6: protein binding. Reason: The physical interactions are real, but GO:0005515 is uninformative and should be replaced by mechanistic ESCRT-II/CHMP4/VPS4 interaction context where possible. Supporting Evidence: PMID:14519844 Each of the putative ESCRT-II components Eap45, Eap30, and Eap20 bound to each other, and to the ESCRT-III protein, CHMP6 PMID:18606141 solution structure of the VPS4A MIT domain in complex with its CHMP6166-181 binding site file:human/CHMP6/CHMP6-notes.md The interactions are real, but GO:0005515 erases the meaningful ESCRT-II, CHMP4, and VPS4 context. |
| GO:0005515 protein binding | IPI PMID:14505570 The protein network of HIV budding. | MARK AS OVER ANNOTATED | Summary: Generic protein binding is over-annotated for CHMP6: protein binding. Reason: The physical interactions are real, but GO:0005515 is uninformative and should be replaced by mechanistic ESCRT-II/CHMP4/VPS4 interaction context where possible. Supporting Evidence: PMID:14519844 Each of the putative ESCRT-II components Eap45, Eap30, and Eap20 bound to each other, and to the ESCRT-III protein, CHMP6 PMID:18606141 solution structure of the VPS4A MIT domain in complex with its CHMP6166-181 binding site file:human/CHMP6/CHMP6-notes.md The interactions are real, but GO:0005515 erases the meaningful ESCRT-II, CHMP4, and VPS4 context. |
| GO:0070062 extracellular exosome | HDA PMID:19056867 Large-scale proteomics and phosphoproteomics of urinary exos... | KEEP AS NON CORE | Summary: Broad proteomics exosome detection is non-core for CHMP6: extracellular exosome. Reason: Extracellular exosome localization from high-throughput proteomics is compatible with ESCRT biology but does not define the CHMP6 core function in MVB cargo sorting. Supporting Evidence: PMID:19056867 Large-scale proteomics and phosphoproteomics of urinary exosomes PMID:20458337 MHC class II-associated proteins in B-cell exosomes file:human/CHMP6/CHMP6-notes.md Keep nuclear envelope sealing/reassembly, nuclear pore, midbody abscission, kinetochore/microtubule, plasma membrane repair, autophagy/macroautophagy/autophagosome/amphisome/lysosomal membrane, cytosol, and extracellular exosome annotations as non-core |
| GO:0070062 extracellular exosome | HDA PMID:20458337 MHC class II-associated proteins in B-cell exosomes and pote... | KEEP AS NON CORE | Summary: Broad proteomics exosome detection is non-core for CHMP6: extracellular exosome. Reason: Extracellular exosome localization from high-throughput proteomics is compatible with ESCRT biology but does not define the CHMP6 core function in MVB cargo sorting. Supporting Evidence: PMID:19056867 Large-scale proteomics and phosphoproteomics of urinary exosomes PMID:20458337 MHC class II-associated proteins in B-cell exosomes file:human/CHMP6/CHMP6-notes.md Keep nuclear envelope sealing/reassembly, nuclear pore, midbody abscission, kinetochore/microtubule, plasma membrane repair, autophagy/macroautophagy/autophagosome/amphisome/lysosomal membrane, cytosol, and extracellular exosome annotations as non-core |
| GO:0005829 cytosol | TAS Reactome:R-HSA-3159232 | KEEP AS NON CORE | Summary: True or plausible broad CHMP6 soluble pool/location: cytosol. Reason: CHMP6 cycles between soluble/inactive and membrane-associated ESCRT assemblies; cytosolic Reactome locations are pathway context, not the core proteostasis function. Supporting Evidence: PMID:17547705 full-length proteins does not file:human/CHMP6/CHMP6-notes.md Keep nuclear envelope sealing/reassembly, nuclear pore, midbody abscission, kinetochore/microtubule, plasma membrane repair, autophagy/macroautophagy/autophagosome/amphisome/lysosomal membrane, cytosol, and extracellular exosome annotations as non-core |
| GO:0005829 cytosol | TAS Reactome:R-HSA-917693 | KEEP AS NON CORE | Summary: True or plausible broad CHMP6 soluble pool/location: cytosol. Reason: CHMP6 cycles between soluble/inactive and membrane-associated ESCRT assemblies; cytosolic Reactome locations are pathway context, not the core proteostasis function. Supporting Evidence: PMID:17547705 full-length proteins does not file:human/CHMP6/CHMP6-notes.md Keep nuclear envelope sealing/reassembly, nuclear pore, midbody abscission, kinetochore/microtubule, plasma membrane repair, autophagy/macroautophagy/autophagosome/amphisome/lysosomal membrane, cytosol, and extracellular exosome annotations as non-core |
| GO:0005829 cytosol | TAS Reactome:R-HSA-917700 | KEEP AS NON CORE | Summary: True or plausible broad CHMP6 soluble pool/location: cytosol. Reason: CHMP6 cycles between soluble/inactive and membrane-associated ESCRT assemblies; cytosolic Reactome locations are pathway context, not the core proteostasis function. Supporting Evidence: PMID:17547705 full-length proteins does not file:human/CHMP6/CHMP6-notes.md Keep nuclear envelope sealing/reassembly, nuclear pore, midbody abscission, kinetochore/microtubule, plasma membrane repair, autophagy/macroautophagy/autophagosome/amphisome/lysosomal membrane, cytosol, and extracellular exosome annotations as non-core |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9668389 | KEEP AS NON CORE | Summary: True or plausible broad CHMP6 soluble pool/location: cytosol. Reason: CHMP6 cycles between soluble/inactive and membrane-associated ESCRT assemblies; cytosolic Reactome locations are pathway context, not the core proteostasis function. Supporting Evidence: PMID:17547705 full-length proteins does not file:human/CHMP6/CHMP6-notes.md Keep nuclear envelope sealing/reassembly, nuclear pore, midbody abscission, kinetochore/microtubule, plasma membrane repair, autophagy/macroautophagy/autophagosome/amphisome/lysosomal membrane, cytosol, and extracellular exosome annotations as non-core |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9668395 | KEEP AS NON CORE | Summary: True or plausible broad CHMP6 soluble pool/location: cytosol. Reason: CHMP6 cycles between soluble/inactive and membrane-associated ESCRT assemblies; cytosolic Reactome locations are pathway context, not the core proteostasis function. Supporting Evidence: PMID:17547705 full-length proteins does not file:human/CHMP6/CHMP6-notes.md Keep nuclear envelope sealing/reassembly, nuclear pore, midbody abscission, kinetochore/microtubule, plasma membrane repair, autophagy/macroautophagy/autophagosome/amphisome/lysosomal membrane, cytosol, and extracellular exosome annotations as non-core |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9668398 | KEEP AS NON CORE | Summary: True or plausible broad CHMP6 soluble pool/location: cytosol. Reason: CHMP6 cycles between soluble/inactive and membrane-associated ESCRT assemblies; cytosolic Reactome locations are pathway context, not the core proteostasis function. Supporting Evidence: PMID:17547705 full-length proteins does not file:human/CHMP6/CHMP6-notes.md Keep nuclear envelope sealing/reassembly, nuclear pore, midbody abscission, kinetochore/microtubule, plasma membrane repair, autophagy/macroautophagy/autophagosome/amphisome/lysosomal membrane, cytosol, and extracellular exosome annotations as non-core |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9668405 | KEEP AS NON CORE | Summary: True or plausible broad CHMP6 soluble pool/location: cytosol. Reason: CHMP6 cycles between soluble/inactive and membrane-associated ESCRT assemblies; cytosolic Reactome locations are pathway context, not the core proteostasis function. Supporting Evidence: PMID:17547705 full-length proteins does not file:human/CHMP6/CHMP6-notes.md Keep nuclear envelope sealing/reassembly, nuclear pore, midbody abscission, kinetochore/microtubule, plasma membrane repair, autophagy/macroautophagy/autophagosome/amphisome/lysosomal membrane, cytosol, and extracellular exosome annotations as non-core |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9668415 | KEEP AS NON CORE | Summary: True or plausible broad CHMP6 soluble pool/location: cytosol. Reason: CHMP6 cycles between soluble/inactive and membrane-associated ESCRT assemblies; cytosolic Reactome locations are pathway context, not the core proteostasis function. Supporting Evidence: PMID:17547705 full-length proteins does not file:human/CHMP6/CHMP6-notes.md Keep nuclear envelope sealing/reassembly, nuclear pore, midbody abscission, kinetochore/microtubule, plasma membrane repair, autophagy/macroautophagy/autophagosome/amphisome/lysosomal membrane, cytosol, and extracellular exosome annotations as non-core |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9668419 | KEEP AS NON CORE | Summary: True or plausible broad CHMP6 soluble pool/location: cytosol. Reason: CHMP6 cycles between soluble/inactive and membrane-associated ESCRT assemblies; cytosolic Reactome locations are pathway context, not the core proteostasis function. Supporting Evidence: PMID:17547705 full-length proteins does not file:human/CHMP6/CHMP6-notes.md Keep nuclear envelope sealing/reassembly, nuclear pore, midbody abscission, kinetochore/microtubule, plasma membrane repair, autophagy/macroautophagy/autophagosome/amphisome/lysosomal membrane, cytosol, and extracellular exosome annotations as non-core |
| GO:0005515 protein binding | IPI PMID:21543490 Mechanism of inhibition of retrovirus release from cells by ... | MARK AS OVER ANNOTATED | Summary: Generic protein binding is over-annotated for CHMP6: protein binding. Reason: The physical interactions are real, but GO:0005515 is uninformative and should be replaced by mechanistic ESCRT-II/CHMP4/VPS4 interaction context where possible. Supporting Evidence: PMID:14519844 Each of the putative ESCRT-II components Eap45, Eap30, and Eap20 bound to each other, and to the ESCRT-III protein, CHMP6 PMID:18606141 solution structure of the VPS4A MIT domain in complex with its CHMP6166-181 binding site file:human/CHMP6/CHMP6-notes.md The interactions are real, but GO:0005515 erases the meaningful ESCRT-II, CHMP4, and VPS4 context. |
| GO:0005515 protein binding | IPI PMID:18606141 Two distinct modes of ESCRT-III recognition are required for... | MARK AS OVER ANNOTATED | Summary: Generic protein binding is over-annotated for CHMP6: protein binding. Reason: The physical interactions are real, but GO:0005515 is uninformative and should be replaced by mechanistic ESCRT-II/CHMP4/VPS4 interaction context where possible. Supporting Evidence: PMID:14519844 Each of the putative ESCRT-II components Eap45, Eap30, and Eap20 bound to each other, and to the ESCRT-III protein, CHMP6 PMID:18606141 solution structure of the VPS4A MIT domain in complex with its CHMP6166-181 binding site file:human/CHMP6/CHMP6-notes.md The interactions are real, but GO:0005515 erases the meaningful ESCRT-II, CHMP4, and VPS4 context. |
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Download this section (compressed HTML)Q: Can endogenous CHMP6 depletion/rescue cleanly separate its ESCRT-II acceptor/nucleator role from later VPS4-mediated ESCRT-III recycling during MVB sorting?
Q: Should CHMP6 viral-budding annotations be removed or generalized to pathway-level ESCRT context given CHMP6-specific depletion data showing no reduction in HIV-1 release?
Q: Which autophagy and nuclear-envelope annotations are directly CHMP6-specific rather than inherited from broad ESCRT-III complex biology?
Experiment: Rescue CHMP6-depleted cells with wild-type, non-myristoylated G2A, ESCRT-II-binding-defective, CHMP4-binding-defective, and MIM2 VPS4-binding-defective CHMP6 while measuring EGFR and ferroportin degradation, MVB ILV cargo incorporation, and ESCRT-III/VPS4 residence times.
Hypothesis: CHMP6-dependent cargo degradation will require membrane association, ESCRT-II/CHMP4 handoff, and VPS4 MIM2-mediated remodeling, with separable effects on initial MVB sorting and later ESCRT-III turnover.
Experiment: Compare acute CHMP6, CHMP4, and VPS4 perturbations in HIV-1 budding, MVB cargo degradation, and plasma membrane repair assays using matched depletion/rescue conditions.
Hypothesis: CHMP6 will be essential or strongly limiting for ESCRT-II-dependent endosomal cargo sorting but less directly required for HIV budding and other ESCRT pathway outputs that can bypass ESCRT-II/CHMP6.
Experiment: Use endogenous tagging and proximity labeling to define when CHMP6 is recruited during starvation autophagy, amphisome formation, and nuclear-envelope repair relative to CHMP7, CHMP4, IST1, and VPS4.
Hypothesis: CHMP6 recruitment in these contexts will be secondary or context-dependent compared with its constitutive role in endosomal ESCRT-II-to-ESCRT-III handoff.
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