id: Q96FZ7 gene_symbol: CHMP6 product_type: PROTEIN status: COMPLETE taxon: id: NCBITaxon:9606 label: Homo sapiens description: >- 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. existing_annotations: - term: id: GO:0005635 label: nuclear envelope evidence_type: IBA original_reference_id: GO_REF:0000033 qualifier: is_active_in review: summary: 'Plausible secondary ESCRT pathway context for CHMP6: nuclear envelope.' action: KEEP_AS_NON_CORE 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. supported_by: - reference_id: file:human/CHMP6/CHMP6-notes.md supporting_text: 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. - term: id: GO:0031468 label: nuclear membrane reassembly evidence_type: IBA original_reference_id: GO_REF:0000033 qualifier: involved_in review: summary: 'Plausible secondary ESCRT pathway context for CHMP6: nuclear membrane reassembly.' action: KEEP_AS_NON_CORE 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. supported_by: - reference_id: file:human/CHMP6/CHMP6-notes.md supporting_text: 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. - term: id: GO:0000815 label: ESCRT III complex evidence_type: IBA original_reference_id: GO_REF:0000033 qualifier: part_of review: summary: 'Supported core CHMP6 ESCRT-III complex membership: ESCRT III complex.' action: ACCEPT 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. supported_by: - reference_id: PMID:15511219 supporting_text: interacts directly with an ESCRT-II component EAP20 and regulates endosomal cargo sorting - reference_id: PMID:14519844 supporting_text: Each of the putative ESCRT-II components Eap45, Eap30, and Eap20 bound to each other, and to the ESCRT-III protein, CHMP6 - reference_id: UniProt:Q96FZ7 supporting_text: probably serves as an acceptor for the ESCRT-II complex on endosomal membranes - reference_id: file:human/CHMP6/CHMP6-notes.md supporting_text: CHMP6 is the human Vps20 ortholog and a core ESCRT-III pathway component. - term: id: GO:0032511 label: late endosome to vacuole transport via multivesicular body sorting pathway evidence_type: IBA original_reference_id: GO_REF:0000033 qualifier: involved_in review: summary: 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. action: MODIFY reason: CHMP6 should be curated to the specific human endosomal MVB sorting and late endosome-to-lysosome transport terms. supported_by: - reference_id: PMID:15511219 supporting_text: CHMP6 acts as an acceptor for ESCRT-II on endosomal membranes and regulates cargo sorting - reference_id: PMID:15511219 supporting_text: Ubiquitinated proteins and endocytosed EGF continuously accumulated in CHMP6-GFP-expressing cells - reference_id: PMID:16973552 supporting_text: inhibited lysosomal targeting and downregulation of the epidermal growth factor receptor - reference_id: PMID:18606141 supporting_text: The CHMP6 MIM2 Binding Site is Required for Ferroportin Degradation - reference_id: file:human/CHMP6/CHMP6-notes.md supporting_text: 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 proposed_replacement_terms: - id: GO:0071985 label: multivesicular body sorting pathway - id: GO:1902774 label: late endosome to lysosome transport - term: id: GO:0000776 label: kinetochore evidence_type: IEA original_reference_id: GO_REF:0000117 qualifier: located_in review: summary: 'Plausible secondary ESCRT pathway context for CHMP6: kinetochore.' action: KEEP_AS_NON_CORE 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. supported_by: - reference_id: file:human/CHMP6/CHMP6-notes.md supporting_text: 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. - term: id: GO:0001778 label: plasma membrane repair evidence_type: IEA original_reference_id: GO_REF:0000117 qualifier: involved_in review: summary: 'Plausible secondary ESCRT pathway context for CHMP6: plasma membrane repair.' action: KEEP_AS_NON_CORE 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. supported_by: - reference_id: file:human/CHMP6/CHMP6-notes.md supporting_text: 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. - term: id: GO:0005643 label: nuclear pore evidence_type: IEA original_reference_id: GO_REF:0000117 qualifier: part_of review: summary: 'Plausible secondary ESCRT pathway context for CHMP6: nuclear pore.' action: KEEP_AS_NON_CORE 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. supported_by: - reference_id: file:human/CHMP6/CHMP6-notes.md supporting_text: 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. - term: id: GO:0005765 label: lysosomal membrane evidence_type: IEA original_reference_id: GO_REF:0000117 qualifier: located_in review: summary: 'Plausible PN-relevant but non-core ESCRT/autophagy context for CHMP6: lysosomal membrane.' action: KEEP_AS_NON_CORE 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. supported_by: - reference_id: PMID:17984323 supporting_text: Functional multivesicular bodies are required for autophagic clearance - reference_id: file:human/CHMP6/CHMP6-notes.md supporting_text: 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 - term: id: GO:0005828 label: kinetochore microtubule evidence_type: IEA original_reference_id: GO_REF:0000117 qualifier: located_in review: summary: 'Plausible secondary ESCRT pathway context for CHMP6: kinetochore microtubule.' action: KEEP_AS_NON_CORE 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. supported_by: - reference_id: file:human/CHMP6/CHMP6-notes.md supporting_text: 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. - term: id: GO:0007034 label: vacuolar transport evidence_type: IEA original_reference_id: GO_REF:0000002 qualifier: involved_in review: summary: The MVB-sorting essence is correct, but vacuolar transport is too broad or non-human-vacuole phrased for CHMP6. action: MODIFY reason: CHMP6 should be curated to the specific human endosomal MVB sorting and late endosome-to-lysosome transport terms. supported_by: - reference_id: PMID:15511219 supporting_text: CHMP6 acts as an acceptor for ESCRT-II on endosomal membranes and regulates cargo sorting - reference_id: PMID:15511219 supporting_text: Ubiquitinated proteins and endocytosed EGF continuously accumulated in CHMP6-GFP-expressing cells - reference_id: PMID:16973552 supporting_text: inhibited lysosomal targeting and downregulation of the epidermal growth factor receptor - reference_id: PMID:18606141 supporting_text: The CHMP6 MIM2 Binding Site is Required for Ferroportin Degradation - reference_id: file:human/CHMP6/CHMP6-notes.md supporting_text: 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 proposed_replacement_terms: - id: GO:0071985 label: multivesicular body sorting pathway - id: GO:1902774 label: late endosome to lysosome transport - term: id: GO:0007080 label: mitotic metaphase chromosome alignment evidence_type: IEA original_reference_id: GO_REF:0000117 qualifier: involved_in review: summary: 'Plausible secondary ESCRT pathway context for CHMP6: mitotic metaphase chromosome alignment.' action: KEEP_AS_NON_CORE 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. supported_by: - reference_id: file:human/CHMP6/CHMP6-notes.md supporting_text: 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. - term: id: GO:0010008 label: endosome membrane evidence_type: IEA original_reference_id: GO_REF:0000044 qualifier: located_in review: summary: 'Supported core CHMP6 endosomal/MVB membrane localization: endosome membrane.' action: ACCEPT reason: CHMP6 is myristoylated and localizes to endosomal/MVB membranes where it links ESCRT-II to ESCRT-III during cargo sorting. supported_by: - reference_id: PMID:15511219 supporting_text: membrane-bound CHMP6-GFP colocalized to endosome-like organelles, including MVBs - reference_id: PMID:15511219 supporting_text: CHMP6 acts as an acceptor for ESCRT-II on endosomal membranes and regulates cargo sorting - reference_id: file:human/CHMP6/CHMP6-notes.md supporting_text: 'Accept as core: ESCRT III complex, ESCRT III complex assembly, endosome/late endosome/MVB membrane localization' - term: id: GO:0012505 label: endomembrane system evidence_type: IEA original_reference_id: GO_REF:0000044 qualifier: located_in review: summary: 'True but broad CHMP6 membrane location: endomembrane system.' action: KEEP_AS_NON_CORE 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. supported_by: - reference_id: PMID:15511219 supporting_text: CHMP6 acts as an acceptor for ESCRT-II on endosomal membranes and regulates cargo sorting - reference_id: file:human/CHMP6/CHMP6-notes.md supporting_text: 'Accept as core: ESCRT III complex, ESCRT III complex assembly, endosome/late endosome/MVB membrane localization' - term: id: GO:0016020 label: membrane evidence_type: IEA original_reference_id: GO_REF:0000044 qualifier: located_in review: summary: 'True but broad CHMP6 membrane location: membrane.' action: KEEP_AS_NON_CORE 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. supported_by: - reference_id: PMID:15511219 supporting_text: CHMP6 acts as an acceptor for ESCRT-II on endosomal membranes and regulates cargo sorting - reference_id: file:human/CHMP6/CHMP6-notes.md supporting_text: 'Accept as core: ESCRT III complex, ESCRT III complex assembly, endosome/late endosome/MVB membrane localization' - term: id: GO:0030496 label: midbody evidence_type: IEA original_reference_id: GO_REF:0000117 qualifier: located_in review: summary: 'Plausible secondary ESCRT pathway context for CHMP6: midbody.' action: KEEP_AS_NON_CORE 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. supported_by: - reference_id: file:human/CHMP6/CHMP6-notes.md supporting_text: 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. - term: id: GO:0031468 label: nuclear membrane reassembly evidence_type: IEA original_reference_id: GO_REF:0000117 qualifier: involved_in review: summary: 'Plausible secondary ESCRT pathway context for CHMP6: nuclear membrane reassembly.' action: KEEP_AS_NON_CORE 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. supported_by: - reference_id: file:human/CHMP6/CHMP6-notes.md supporting_text: 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. - term: id: GO:0031902 label: late endosome membrane evidence_type: IEA original_reference_id: GO_REF:0000044 qualifier: located_in review: summary: 'Supported core CHMP6 endosomal/MVB membrane localization: late endosome membrane.' action: ACCEPT reason: CHMP6 is myristoylated and localizes to endosomal/MVB membranes where it links ESCRT-II to ESCRT-III during cargo sorting. supported_by: - reference_id: PMID:15511219 supporting_text: membrane-bound CHMP6-GFP colocalized to endosome-like organelles, including MVBs - reference_id: PMID:15511219 supporting_text: CHMP6 acts as an acceptor for ESCRT-II on endosomal membranes and regulates cargo sorting - reference_id: file:human/CHMP6/CHMP6-notes.md supporting_text: 'Accept as core: ESCRT III complex, ESCRT III complex assembly, endosome/late endosome/MVB membrane localization' - term: id: GO:0032585 label: multivesicular body membrane evidence_type: IEA original_reference_id: GO_REF:0000117 qualifier: located_in review: summary: 'Supported core CHMP6 endosomal/MVB membrane localization: multivesicular body membrane.' action: ACCEPT reason: CHMP6 is myristoylated and localizes to endosomal/MVB membranes where it links ESCRT-II to ESCRT-III during cargo sorting. supported_by: - reference_id: PMID:15511219 supporting_text: membrane-bound CHMP6-GFP colocalized to endosome-like organelles, including MVBs - reference_id: PMID:15511219 supporting_text: CHMP6 acts as an acceptor for ESCRT-II on endosomal membranes and regulates cargo sorting - reference_id: file:human/CHMP6/CHMP6-notes.md supporting_text: 'Accept as core: ESCRT III complex, ESCRT III complex assembly, endosome/late endosome/MVB membrane localization' - term: id: GO:0039702 label: viral budding via host ESCRT complex evidence_type: IEA original_reference_id: GO_REF:0000117 qualifier: involved_in review: summary: 'Over-annotated CHMP6 viral-budding term: viral budding via host ESCRT complex.' action: MARK_AS_OVER_ANNOTATED 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. supported_by: - reference_id: PMID:16973552 supporting_text: HIV-1 release and infectivity were not reduced by efficient small interfering RNA depletion of EAP20/ESCRT-II or CHMP6/ESCRT-III - reference_id: PMID:18606141 supporting_text: Several ESCRT functions, including HIV budding, are insensitive to CHMP6 depletion - reference_id: PMID:14519844 supporting_text: nor did the ESCRT-II-binding component of ESCRT-III, CHMP6 - reference_id: file:human/CHMP6/CHMP6-notes.md supporting_text: Treat viral budding as over-annotated for CHMP6. - term: id: GO:0043162 label: ubiquitin-dependent protein catabolic process via the multivesicular body sorting pathway evidence_type: IEA original_reference_id: GO_REF:0000117 qualifier: involved_in review: summary: 'Supported core CHMP6 endolysosomal cargo-sorting process: ubiquitin-dependent protein catabolic process via the multivesicular body sorting pathway.' action: ACCEPT reason: CHMP6-specific evidence supports MVB sorting and downstream lysosomal degradation of endocytosed/ubiquitinated membrane cargo. supported_by: - reference_id: PMID:15511219 supporting_text: CHMP6 acts as an acceptor for ESCRT-II on endosomal membranes and regulates cargo sorting - reference_id: PMID:15511219 supporting_text: Ubiquitinated proteins and endocytosed EGF continuously accumulated in CHMP6-GFP-expressing cells - reference_id: PMID:16973552 supporting_text: inhibited lysosomal targeting and downregulation of the epidermal growth factor receptor - reference_id: PMID:18606141 supporting_text: The CHMP6 MIM2 Binding Site is Required for Ferroportin Degradation - reference_id: file:human/CHMP6/CHMP6-notes.md supporting_text: 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 - term: id: GO:0046761 label: viral budding from plasma membrane evidence_type: IEA original_reference_id: GO_REF:0000117 qualifier: involved_in review: summary: 'Over-annotated CHMP6 viral-budding term: viral budding from plasma membrane.' action: MARK_AS_OVER_ANNOTATED 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. supported_by: - reference_id: PMID:16973552 supporting_text: HIV-1 release and infectivity were not reduced by efficient small interfering RNA depletion of EAP20/ESCRT-II or CHMP6/ESCRT-III - reference_id: PMID:18606141 supporting_text: Several ESCRT functions, including HIV budding, are insensitive to CHMP6 depletion - reference_id: PMID:14519844 supporting_text: nor did the ESCRT-II-binding component of ESCRT-III, CHMP6 - reference_id: file:human/CHMP6/CHMP6-notes.md supporting_text: Treat viral budding as over-annotated for CHMP6. - term: id: GO:0061952 label: midbody abscission evidence_type: IEA original_reference_id: GO_REF:0000117 qualifier: involved_in review: summary: 'Plausible secondary ESCRT pathway context for CHMP6: midbody abscission.' action: KEEP_AS_NON_CORE 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. supported_by: - reference_id: file:human/CHMP6/CHMP6-notes.md supporting_text: 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. - term: id: GO:0071985 label: multivesicular body sorting pathway evidence_type: IEA original_reference_id: GO_REF:0000117 qualifier: involved_in review: summary: 'Supported core CHMP6 endolysosomal cargo-sorting process: multivesicular body sorting pathway.' action: ACCEPT reason: CHMP6-specific evidence supports MVB sorting and downstream lysosomal degradation of endocytosed/ubiquitinated membrane cargo. supported_by: - reference_id: PMID:15511219 supporting_text: CHMP6 acts as an acceptor for ESCRT-II on endosomal membranes and regulates cargo sorting - reference_id: PMID:15511219 supporting_text: Ubiquitinated proteins and endocytosed EGF continuously accumulated in CHMP6-GFP-expressing cells - reference_id: PMID:16973552 supporting_text: inhibited lysosomal targeting and downregulation of the epidermal growth factor receptor - reference_id: PMID:18606141 supporting_text: The CHMP6 MIM2 Binding Site is Required for Ferroportin Degradation - reference_id: file:human/CHMP6/CHMP6-notes.md supporting_text: 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 - term: id: GO:0097352 label: autophagosome maturation evidence_type: IEA original_reference_id: GO_REF:0000117 qualifier: involved_in review: summary: 'Plausible PN-relevant but non-core ESCRT/autophagy context for CHMP6: autophagosome maturation.' action: KEEP_AS_NON_CORE 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. supported_by: - reference_id: PMID:17984323 supporting_text: Functional multivesicular bodies are required for autophagic clearance - reference_id: file:human/CHMP6/CHMP6-notes.md supporting_text: 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 - term: id: GO:1901673 label: regulation of mitotic spindle assembly evidence_type: IEA original_reference_id: GO_REF:0000117 qualifier: involved_in review: summary: 'Plausible secondary ESCRT pathway context for CHMP6: regulation of mitotic spindle assembly.' action: KEEP_AS_NON_CORE 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. supported_by: - reference_id: file:human/CHMP6/CHMP6-notes.md supporting_text: 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. - term: id: GO:1902774 label: late endosome to lysosome transport evidence_type: IEA original_reference_id: GO_REF:0000117 qualifier: involved_in review: summary: 'Supported core CHMP6 endolysosomal cargo-sorting process: late endosome to lysosome transport.' action: ACCEPT reason: CHMP6-specific evidence supports MVB sorting and downstream lysosomal degradation of endocytosed/ubiquitinated membrane cargo. supported_by: - reference_id: PMID:15511219 supporting_text: CHMP6 acts as an acceptor for ESCRT-II on endosomal membranes and regulates cargo sorting - reference_id: PMID:15511219 supporting_text: Ubiquitinated proteins and endocytosed EGF continuously accumulated in CHMP6-GFP-expressing cells - reference_id: PMID:16973552 supporting_text: inhibited lysosomal targeting and downregulation of the epidermal growth factor receptor - reference_id: PMID:18606141 supporting_text: The CHMP6 MIM2 Binding Site is Required for Ferroportin Degradation - reference_id: file:human/CHMP6/CHMP6-notes.md supporting_text: 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 - term: id: GO:1904930 label: amphisome membrane evidence_type: IEA original_reference_id: GO_REF:0000117 qualifier: located_in review: summary: 'Plausible PN-relevant but non-core ESCRT/autophagy context for CHMP6: amphisome membrane.' action: KEEP_AS_NON_CORE 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. supported_by: - reference_id: PMID:17984323 supporting_text: Functional multivesicular bodies are required for autophagic clearance - reference_id: file:human/CHMP6/CHMP6-notes.md supporting_text: 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 - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:16730941 qualifier: enables review: summary: 'Generic protein binding is over-annotated for CHMP6: protein binding.' action: MARK_AS_OVER_ANNOTATED 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. supported_by: - reference_id: PMID:14519844 supporting_text: Each of the putative ESCRT-II components Eap45, Eap30, and Eap20 bound to each other, and to the ESCRT-III protein, CHMP6 - reference_id: PMID:18606141 supporting_text: solution structure of the VPS4A MIT domain in complex with its CHMP6166-181 binding site - reference_id: file:human/CHMP6/CHMP6-notes.md supporting_text: The interactions are real, but GO:0005515 erases the meaningful ESCRT-II, CHMP4, and VPS4 context. - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:16856878 qualifier: enables review: summary: 'Generic protein binding is over-annotated for CHMP6: protein binding.' action: MARK_AS_OVER_ANNOTATED 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. supported_by: - reference_id: PMID:14519844 supporting_text: Each of the putative ESCRT-II components Eap45, Eap30, and Eap20 bound to each other, and to the ESCRT-III protein, CHMP6 - reference_id: PMID:18606141 supporting_text: solution structure of the VPS4A MIT domain in complex with its CHMP6166-181 binding site - reference_id: file:human/CHMP6/CHMP6-notes.md supporting_text: The interactions are real, but GO:0005515 erases the meaningful ESCRT-II, CHMP4, and VPS4 context. - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:32296183 qualifier: enables review: summary: 'Generic protein binding is over-annotated for CHMP6: protein binding.' action: MARK_AS_OVER_ANNOTATED 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. supported_by: - reference_id: PMID:14519844 supporting_text: Each of the putative ESCRT-II components Eap45, Eap30, and Eap20 bound to each other, and to the ESCRT-III protein, CHMP6 - reference_id: PMID:18606141 supporting_text: solution structure of the VPS4A MIT domain in complex with its CHMP6166-181 binding site - reference_id: file:human/CHMP6/CHMP6-notes.md supporting_text: The interactions are real, but GO:0005515 erases the meaningful ESCRT-II, CHMP4, and VPS4 context. - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:32814053 qualifier: enables review: summary: 'Generic protein binding is over-annotated for CHMP6: protein binding.' action: MARK_AS_OVER_ANNOTATED 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. supported_by: - reference_id: PMID:14519844 supporting_text: Each of the putative ESCRT-II components Eap45, Eap30, and Eap20 bound to each other, and to the ESCRT-III protein, CHMP6 - reference_id: PMID:18606141 supporting_text: solution structure of the VPS4A MIT domain in complex with its CHMP6166-181 binding site - reference_id: file:human/CHMP6/CHMP6-notes.md supporting_text: The interactions are real, but GO:0005515 erases the meaningful ESCRT-II, CHMP4, and VPS4 context. - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:33961781 qualifier: enables review: summary: 'Generic protein binding is over-annotated for CHMP6: protein binding.' action: MARK_AS_OVER_ANNOTATED 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. supported_by: - reference_id: PMID:14519844 supporting_text: Each of the putative ESCRT-II components Eap45, Eap30, and Eap20 bound to each other, and to the ESCRT-III protein, CHMP6 - reference_id: PMID:18606141 supporting_text: solution structure of the VPS4A MIT domain in complex with its CHMP6166-181 binding site - reference_id: file:human/CHMP6/CHMP6-notes.md supporting_text: The interactions are real, but GO:0005515 erases the meaningful ESCRT-II, CHMP4, and VPS4 context. - term: id: GO:0000421 label: autophagosome membrane evidence_type: IDA original_reference_id: PMID:17984323 qualifier: located_in review: summary: 'Plausible PN-relevant but non-core ESCRT/autophagy context for CHMP6: autophagosome membrane.' action: KEEP_AS_NON_CORE 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. supported_by: - reference_id: PMID:17984323 supporting_text: Functional multivesicular bodies are required for autophagic clearance - reference_id: file:human/CHMP6/CHMP6-notes.md supporting_text: 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 - term: id: GO:0000776 label: kinetochore evidence_type: IDA original_reference_id: PMID:26040712 qualifier: located_in review: summary: 'Plausible secondary ESCRT pathway context for CHMP6: kinetochore.' action: KEEP_AS_NON_CORE 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. supported_by: - reference_id: file:human/CHMP6/CHMP6-notes.md supporting_text: 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. - term: id: GO:0000815 label: ESCRT III complex evidence_type: NAS original_reference_id: PMID:36107470 qualifier: part_of review: summary: 'Supported core CHMP6 ESCRT-III complex membership: ESCRT III complex.' action: ACCEPT 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. supported_by: - reference_id: PMID:15511219 supporting_text: interacts directly with an ESCRT-II component EAP20 and regulates endosomal cargo sorting - reference_id: PMID:14519844 supporting_text: Each of the putative ESCRT-II components Eap45, Eap30, and Eap20 bound to each other, and to the ESCRT-III protein, CHMP6 - reference_id: UniProt:Q96FZ7 supporting_text: probably serves as an acceptor for the ESCRT-II complex on endosomal membranes - reference_id: file:human/CHMP6/CHMP6-notes.md supporting_text: CHMP6 is the human Vps20 ortholog and a core ESCRT-III pathway component. - term: id: GO:0001778 label: plasma membrane repair evidence_type: IDA original_reference_id: PMID:24482116 qualifier: involved_in review: summary: 'Plausible secondary ESCRT pathway context for CHMP6: plasma membrane repair.' action: KEEP_AS_NON_CORE 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. supported_by: - reference_id: file:human/CHMP6/CHMP6-notes.md supporting_text: 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. - term: id: GO:0005643 label: nuclear pore evidence_type: IDA original_reference_id: PMID:26040713 qualifier: part_of review: summary: 'Plausible secondary ESCRT pathway context for CHMP6: nuclear pore.' action: KEEP_AS_NON_CORE 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. supported_by: - reference_id: file:human/CHMP6/CHMP6-notes.md supporting_text: 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. - term: id: GO:0005765 label: lysosomal membrane evidence_type: IDA original_reference_id: PMID:17984323 qualifier: located_in review: summary: 'Plausible PN-relevant but non-core ESCRT/autophagy context for CHMP6: lysosomal membrane.' action: KEEP_AS_NON_CORE 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. supported_by: - reference_id: PMID:17984323 supporting_text: Functional multivesicular bodies are required for autophagic clearance - reference_id: file:human/CHMP6/CHMP6-notes.md supporting_text: 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 - term: id: GO:0005828 label: kinetochore microtubule evidence_type: IDA original_reference_id: PMID:26040712 qualifier: located_in review: summary: 'Plausible secondary ESCRT pathway context for CHMP6: kinetochore microtubule.' action: KEEP_AS_NON_CORE 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. supported_by: - reference_id: file:human/CHMP6/CHMP6-notes.md supporting_text: 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. - term: id: GO:0005886 label: plasma membrane evidence_type: IDA original_reference_id: PMID:24878737 qualifier: located_in review: summary: 'Plausible secondary ESCRT pathway context for CHMP6: plasma membrane.' action: KEEP_AS_NON_CORE 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. supported_by: - reference_id: file:human/CHMP6/CHMP6-notes.md supporting_text: 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. - term: id: GO:0006914 label: autophagy evidence_type: IMP original_reference_id: PMID:17984323 qualifier: involved_in review: summary: 'Plausible PN-relevant but non-core ESCRT/autophagy context for CHMP6: autophagy.' action: KEEP_AS_NON_CORE 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. supported_by: - reference_id: PMID:17984323 supporting_text: Functional multivesicular bodies are required for autophagic clearance - reference_id: file:human/CHMP6/CHMP6-notes.md supporting_text: 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 - term: id: GO:0006997 label: nucleus organization evidence_type: IMP original_reference_id: PMID:20616062 qualifier: involved_in review: summary: 'Plausible secondary ESCRT pathway context for CHMP6: nucleus organization.' action: KEEP_AS_NON_CORE 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. supported_by: - reference_id: file:human/CHMP6/CHMP6-notes.md supporting_text: 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. - term: id: GO:0007080 label: mitotic metaphase chromosome alignment evidence_type: IMP original_reference_id: PMID:20616062 qualifier: involved_in review: summary: 'Plausible secondary ESCRT pathway context for CHMP6: mitotic metaphase chromosome alignment.' action: KEEP_AS_NON_CORE 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. supported_by: - reference_id: file:human/CHMP6/CHMP6-notes.md supporting_text: 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. - term: id: GO:0030496 label: midbody evidence_type: IDA original_reference_id: PMID:26040712 qualifier: located_in review: summary: 'Plausible secondary ESCRT pathway context for CHMP6: midbody.' action: KEEP_AS_NON_CORE 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. supported_by: - reference_id: file:human/CHMP6/CHMP6-notes.md supporting_text: 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. - term: id: GO:0031468 label: nuclear membrane reassembly evidence_type: IMP original_reference_id: PMID:26040713 qualifier: involved_in review: summary: 'Plausible secondary ESCRT pathway context for CHMP6: nuclear membrane reassembly.' action: KEEP_AS_NON_CORE 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. supported_by: - reference_id: file:human/CHMP6/CHMP6-notes.md supporting_text: 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. - term: id: GO:0032585 label: multivesicular body membrane evidence_type: IDA original_reference_id: PMID:16554368 qualifier: located_in review: summary: 'Supported core CHMP6 endosomal/MVB membrane localization: multivesicular body membrane.' action: ACCEPT reason: CHMP6 is myristoylated and localizes to endosomal/MVB membranes where it links ESCRT-II to ESCRT-III during cargo sorting. supported_by: - reference_id: PMID:15511219 supporting_text: membrane-bound CHMP6-GFP colocalized to endosome-like organelles, including MVBs - reference_id: PMID:15511219 supporting_text: CHMP6 acts as an acceptor for ESCRT-II on endosomal membranes and regulates cargo sorting - reference_id: file:human/CHMP6/CHMP6-notes.md supporting_text: 'Accept as core: ESCRT III complex, ESCRT III complex assembly, endosome/late endosome/MVB membrane localization' - term: id: GO:0036258 label: multivesicular body assembly evidence_type: NAS original_reference_id: PMID:16505166 qualifier: involved_in review: summary: 'Supported core CHMP6 endolysosomal cargo-sorting process: multivesicular body assembly.' action: ACCEPT reason: CHMP6-specific evidence supports MVB sorting and downstream lysosomal degradation of endocytosed/ubiquitinated membrane cargo. supported_by: - reference_id: PMID:15511219 supporting_text: CHMP6 acts as an acceptor for ESCRT-II on endosomal membranes and regulates cargo sorting - reference_id: PMID:15511219 supporting_text: Ubiquitinated proteins and endocytosed EGF continuously accumulated in CHMP6-GFP-expressing cells - reference_id: PMID:16973552 supporting_text: inhibited lysosomal targeting and downregulation of the epidermal growth factor receptor - reference_id: PMID:18606141 supporting_text: The CHMP6 MIM2 Binding Site is Required for Ferroportin Degradation - reference_id: file:human/CHMP6/CHMP6-notes.md supporting_text: 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 - term: id: GO:0039702 label: viral budding via host ESCRT complex evidence_type: IDA original_reference_id: PMID:24878737 qualifier: involved_in review: summary: 'Over-annotated CHMP6 viral-budding term: viral budding via host ESCRT complex.' action: MARK_AS_OVER_ANNOTATED 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. supported_by: - reference_id: PMID:16973552 supporting_text: HIV-1 release and infectivity were not reduced by efficient small interfering RNA depletion of EAP20/ESCRT-II or CHMP6/ESCRT-III - reference_id: PMID:18606141 supporting_text: Several ESCRT functions, including HIV budding, are insensitive to CHMP6 depletion - reference_id: PMID:14519844 supporting_text: nor did the ESCRT-II-binding component of ESCRT-III, CHMP6 - reference_id: file:human/CHMP6/CHMP6-notes.md supporting_text: Treat viral budding as over-annotated for CHMP6. - term: id: GO:0043162 label: ubiquitin-dependent protein catabolic process via the multivesicular body sorting pathway evidence_type: IDA original_reference_id: PMID:17984323 qualifier: involved_in review: summary: 'Supported core CHMP6 endolysosomal cargo-sorting process: ubiquitin-dependent protein catabolic process via the multivesicular body sorting pathway.' action: ACCEPT reason: CHMP6-specific evidence supports MVB sorting and downstream lysosomal degradation of endocytosed/ubiquitinated membrane cargo. supported_by: - reference_id: PMID:15511219 supporting_text: CHMP6 acts as an acceptor for ESCRT-II on endosomal membranes and regulates cargo sorting - reference_id: PMID:15511219 supporting_text: Ubiquitinated proteins and endocytosed EGF continuously accumulated in CHMP6-GFP-expressing cells - reference_id: PMID:16973552 supporting_text: inhibited lysosomal targeting and downregulation of the epidermal growth factor receptor - reference_id: PMID:18606141 supporting_text: The CHMP6 MIM2 Binding Site is Required for Ferroportin Degradation - reference_id: file:human/CHMP6/CHMP6-notes.md supporting_text: 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 - term: id: GO:0046761 label: viral budding from plasma membrane evidence_type: IDA original_reference_id: PMID:24878737 qualifier: involved_in review: summary: 'Over-annotated CHMP6 viral-budding term: viral budding from plasma membrane.' action: MARK_AS_OVER_ANNOTATED 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. supported_by: - reference_id: PMID:16973552 supporting_text: HIV-1 release and infectivity were not reduced by efficient small interfering RNA depletion of EAP20/ESCRT-II or CHMP6/ESCRT-III - reference_id: PMID:18606141 supporting_text: Several ESCRT functions, including HIV budding, are insensitive to CHMP6 depletion - reference_id: PMID:14519844 supporting_text: nor did the ESCRT-II-binding component of ESCRT-III, CHMP6 - reference_id: file:human/CHMP6/CHMP6-notes.md supporting_text: Treat viral budding as over-annotated for CHMP6. - term: id: GO:0051469 label: vesicle fusion with vacuole evidence_type: NAS original_reference_id: PMID:16505166 qualifier: involved_in review: summary: 'This transport/fusion annotation should be replaced with the better-supported CHMP6 endolysosomal cargo-sorting route: vesicle fusion with vacuole.' action: MODIFY reason: The evidence supports MVB sorting and delivery toward lysosomal degradation, not a CHMP6-specific vesicle-fusion activity. supported_by: - reference_id: PMID:15511219 supporting_text: CHMP6 acts as an acceptor for ESCRT-II on endosomal membranes and regulates cargo sorting - reference_id: PMID:15511219 supporting_text: Ubiquitinated proteins and endocytosed EGF continuously accumulated in CHMP6-GFP-expressing cells - reference_id: PMID:16973552 supporting_text: inhibited lysosomal targeting and downregulation of the epidermal growth factor receptor - reference_id: PMID:18606141 supporting_text: The CHMP6 MIM2 Binding Site is Required for Ferroportin Degradation - reference_id: file:human/CHMP6/CHMP6-notes.md supporting_text: 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 proposed_replacement_terms: - id: GO:1902774 label: late endosome to lysosome transport - term: id: GO:0061763 label: multivesicular body-lysosome fusion evidence_type: NAS original_reference_id: PMID:16505166 qualifier: involved_in review: summary: 'This transport/fusion annotation should be replaced with the better-supported CHMP6 endolysosomal cargo-sorting route: multivesicular body-lysosome fusion.' action: MODIFY reason: The evidence supports MVB sorting and delivery toward lysosomal degradation, not a CHMP6-specific vesicle-fusion activity. supported_by: - reference_id: PMID:15511219 supporting_text: CHMP6 acts as an acceptor for ESCRT-II on endosomal membranes and regulates cargo sorting - reference_id: PMID:15511219 supporting_text: Ubiquitinated proteins and endocytosed EGF continuously accumulated in CHMP6-GFP-expressing cells - reference_id: PMID:16973552 supporting_text: inhibited lysosomal targeting and downregulation of the epidermal growth factor receptor - reference_id: PMID:18606141 supporting_text: The CHMP6 MIM2 Binding Site is Required for Ferroportin Degradation - reference_id: file:human/CHMP6/CHMP6-notes.md supporting_text: 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 proposed_replacement_terms: - id: GO:1902774 label: late endosome to lysosome transport - term: id: GO:0061952 label: midbody abscission evidence_type: IMP original_reference_id: PMID:20616062 qualifier: involved_in review: summary: 'Plausible secondary ESCRT pathway context for CHMP6: midbody abscission.' action: KEEP_AS_NON_CORE 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. supported_by: - reference_id: file:human/CHMP6/CHMP6-notes.md supporting_text: 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. - term: id: GO:0071985 label: multivesicular body sorting pathway evidence_type: IDA original_reference_id: PMID:16554368 qualifier: involved_in review: summary: 'Supported core CHMP6 endolysosomal cargo-sorting process: multivesicular body sorting pathway.' action: ACCEPT reason: CHMP6-specific evidence supports MVB sorting and downstream lysosomal degradation of endocytosed/ubiquitinated membrane cargo. supported_by: - reference_id: PMID:15511219 supporting_text: CHMP6 acts as an acceptor for ESCRT-II on endosomal membranes and regulates cargo sorting - reference_id: PMID:15511219 supporting_text: Ubiquitinated proteins and endocytosed EGF continuously accumulated in CHMP6-GFP-expressing cells - reference_id: PMID:16973552 supporting_text: inhibited lysosomal targeting and downregulation of the epidermal growth factor receptor - reference_id: PMID:18606141 supporting_text: The CHMP6 MIM2 Binding Site is Required for Ferroportin Degradation - reference_id: file:human/CHMP6/CHMP6-notes.md supporting_text: 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 - term: id: GO:0090148 label: membrane fission evidence_type: NAS original_reference_id: PMID:19234443 qualifier: involved_in review: summary: 'Supported pathway-level ESCRT-III membrane-fission output for CHMP6: membrane fission.' action: ACCEPT 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. supported_by: - reference_id: PMID:18606141 supporting_text: VPS4 and ESCRT-III might work together to produce the constriction necessary for vesicle extrusion and/or membrane fission - reference_id: PMID:17547705 supporting_text: 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 - reference_id: file:human/CHMP6/CHMP6-notes.md supporting_text: 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 - term: id: GO:0097352 label: autophagosome maturation evidence_type: IMP original_reference_id: PMID:17984323 qualifier: involved_in review: summary: 'Plausible PN-relevant but non-core ESCRT/autophagy context for CHMP6: autophagosome maturation.' action: KEEP_AS_NON_CORE 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. supported_by: - reference_id: PMID:17984323 supporting_text: Functional multivesicular bodies are required for autophagic clearance - reference_id: file:human/CHMP6/CHMP6-notes.md supporting_text: 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 - term: id: GO:1901673 label: regulation of mitotic spindle assembly evidence_type: IMP original_reference_id: PMID:20616062 qualifier: involved_in review: summary: 'Plausible secondary ESCRT pathway context for CHMP6: regulation of mitotic spindle assembly.' action: KEEP_AS_NON_CORE 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. supported_by: - reference_id: file:human/CHMP6/CHMP6-notes.md supporting_text: 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. - term: id: GO:1902774 label: late endosome to lysosome transport evidence_type: IMP original_reference_id: PMID:17984323 qualifier: involved_in review: summary: 'Supported core CHMP6 endolysosomal cargo-sorting process: late endosome to lysosome transport.' action: ACCEPT reason: CHMP6-specific evidence supports MVB sorting and downstream lysosomal degradation of endocytosed/ubiquitinated membrane cargo. supported_by: - reference_id: PMID:15511219 supporting_text: CHMP6 acts as an acceptor for ESCRT-II on endosomal membranes and regulates cargo sorting - reference_id: PMID:15511219 supporting_text: Ubiquitinated proteins and endocytosed EGF continuously accumulated in CHMP6-GFP-expressing cells - reference_id: PMID:16973552 supporting_text: inhibited lysosomal targeting and downregulation of the epidermal growth factor receptor - reference_id: PMID:18606141 supporting_text: The CHMP6 MIM2 Binding Site is Required for Ferroportin Degradation - reference_id: file:human/CHMP6/CHMP6-notes.md supporting_text: 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 - term: id: GO:1904930 label: amphisome membrane evidence_type: IDA original_reference_id: PMID:17984323 qualifier: located_in review: summary: 'Plausible PN-relevant but non-core ESCRT/autophagy context for CHMP6: amphisome membrane.' action: KEEP_AS_NON_CORE 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. supported_by: - reference_id: PMID:17984323 supporting_text: Functional multivesicular bodies are required for autophagic clearance - reference_id: file:human/CHMP6/CHMP6-notes.md supporting_text: 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 - term: id: GO:0042176 label: regulation of protein catabolic process evidence_type: IMP original_reference_id: PMID:18606141 qualifier: involved_in review: summary: 'The protein-catabolism concept is correct but should be made CHMP6-specific: regulation of protein catabolic process.' action: MODIFY reason: Ferroportin and EGFR evidence supports ubiquitin-dependent MVB cargo sorting and late endosome-to-lysosome delivery, not general regulation of protein catabolism. supported_by: - reference_id: PMID:15511219 supporting_text: CHMP6 acts as an acceptor for ESCRT-II on endosomal membranes and regulates cargo sorting - reference_id: PMID:15511219 supporting_text: Ubiquitinated proteins and endocytosed EGF continuously accumulated in CHMP6-GFP-expressing cells - reference_id: PMID:16973552 supporting_text: inhibited lysosomal targeting and downregulation of the epidermal growth factor receptor - reference_id: PMID:18606141 supporting_text: The CHMP6 MIM2 Binding Site is Required for Ferroportin Degradation - reference_id: file:human/CHMP6/CHMP6-notes.md supporting_text: 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 proposed_replacement_terms: - id: GO:0043162 label: ubiquitin-dependent protein catabolic process via the multivesicular body sorting pathway - id: GO:1902774 label: late endosome to lysosome transport - term: id: GO:0007175 label: negative regulation of epidermal growth factor-activated receptor activity evidence_type: IMP original_reference_id: PMID:16973552 qualifier: involved_in review: summary: 'Supported cargo-specific consequence of CHMP6 MVB sorting: negative regulation of epidermal growth factor-activated receptor activity.' action: ACCEPT 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. supported_by: - reference_id: PMID:16973552 supporting_text: inhibited lysosomal targeting and downregulation of the epidermal growth factor receptor - reference_id: PMID:15511219 supporting_text: endocytosed EGF continuously accumulated in CHMP6-GFP-expressing cells - reference_id: file:human/CHMP6/CHMP6-notes.md supporting_text: 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 - term: id: GO:0044877 label: protein-containing complex binding evidence_type: IDA original_reference_id: PMID:16973552 qualifier: enables review: summary: 'Supported CHMP6 ESCRT protein-complex binding mechanism: protein-containing complex binding.' action: ACCEPT 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. supported_by: - reference_id: PMID:15511219 supporting_text: Interactions of CHMP6 with another ESCRT-III component CHMP4b/Shax - reference_id: PMID:16973552 supporting_text: EAP20 bound the N-terminal half of CHMP6/ESCRT-III - reference_id: PMID:18606141 supporting_text: solution structure of the VPS4A MIT domain in complex with its CHMP6166-181 binding site - reference_id: file:human/CHMP6/CHMP6-notes.md supporting_text: protein-containing complex binding where it reflects ESCRT-II/ESCRT-III handoff rather than generic binding - term: id: GO:0016236 label: macroautophagy evidence_type: TAS original_reference_id: PMID:20588296 qualifier: involved_in review: summary: 'Plausible PN-relevant but non-core ESCRT/autophagy context for CHMP6: macroautophagy.' action: KEEP_AS_NON_CORE 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. supported_by: - reference_id: PMID:17984323 supporting_text: Functional multivesicular bodies are required for autophagic clearance - reference_id: file:human/CHMP6/CHMP6-notes.md supporting_text: 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 - term: id: GO:0000815 label: ESCRT III complex evidence_type: TAS original_reference_id: PMID:20588296 qualifier: part_of review: summary: 'Supported core CHMP6 ESCRT-III complex membership: ESCRT III complex.' action: ACCEPT 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. supported_by: - reference_id: PMID:15511219 supporting_text: interacts directly with an ESCRT-II component EAP20 and regulates endosomal cargo sorting - reference_id: PMID:14519844 supporting_text: Each of the putative ESCRT-II components Eap45, Eap30, and Eap20 bound to each other, and to the ESCRT-III protein, CHMP6 - reference_id: UniProt:Q96FZ7 supporting_text: probably serves as an acceptor for the ESCRT-II complex on endosomal membranes - reference_id: file:human/CHMP6/CHMP6-notes.md supporting_text: CHMP6 is the human Vps20 ortholog and a core ESCRT-III pathway component. - term: id: GO:0036258 label: multivesicular body assembly evidence_type: TAS original_reference_id: PMID:20588296 qualifier: involved_in review: summary: 'Supported core CHMP6 endolysosomal cargo-sorting process: multivesicular body assembly.' action: ACCEPT reason: CHMP6-specific evidence supports MVB sorting and downstream lysosomal degradation of endocytosed/ubiquitinated membrane cargo. supported_by: - reference_id: PMID:15511219 supporting_text: CHMP6 acts as an acceptor for ESCRT-II on endosomal membranes and regulates cargo sorting - reference_id: PMID:15511219 supporting_text: Ubiquitinated proteins and endocytosed EGF continuously accumulated in CHMP6-GFP-expressing cells - reference_id: PMID:16973552 supporting_text: inhibited lysosomal targeting and downregulation of the epidermal growth factor receptor - reference_id: PMID:18606141 supporting_text: The CHMP6 MIM2 Binding Site is Required for Ferroportin Degradation - reference_id: file:human/CHMP6/CHMP6-notes.md supporting_text: 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 - term: id: GO:1904902 label: ESCRT III complex assembly evidence_type: NAS original_reference_id: PMID:20588296 qualifier: involved_in review: summary: 'Supported core CHMP6 role in ESCRT-III assembly/remodeling: ESCRT III complex assembly.' action: ACCEPT 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. supported_by: - reference_id: PMID:15511219 supporting_text: interactions between CHMP6 and CHMP4b as well as between CHMP6 and EAP20 - reference_id: PMID:17547705 supporting_text: 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 - reference_id: PMID:18606141 supporting_text: both MIM1 and MIM2 interactions contribute in recruiting VPS4A to endosomal membranes - reference_id: file:human/CHMP6/CHMP6-notes.md supporting_text: CHMP6 has a conserved ESCRT-III autoinhibited/open behavior. - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:16973552 qualifier: enables review: summary: 'Generic protein binding is over-annotated for CHMP6: protein binding.' action: MARK_AS_OVER_ANNOTATED 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. supported_by: - reference_id: PMID:14519844 supporting_text: Each of the putative ESCRT-II components Eap45, Eap30, and Eap20 bound to each other, and to the ESCRT-III protein, CHMP6 - reference_id: PMID:18606141 supporting_text: solution structure of the VPS4A MIT domain in complex with its CHMP6166-181 binding site - reference_id: file:human/CHMP6/CHMP6-notes.md supporting_text: The interactions are real, but GO:0005515 erases the meaningful ESCRT-II, CHMP4, and VPS4 context. - term: id: GO:0010008 label: endosome membrane evidence_type: IDA original_reference_id: PMID:16973552 qualifier: located_in review: summary: 'Supported core CHMP6 endosomal/MVB membrane localization: endosome membrane.' action: ACCEPT reason: CHMP6 is myristoylated and localizes to endosomal/MVB membranes where it links ESCRT-II to ESCRT-III during cargo sorting. supported_by: - reference_id: PMID:15511219 supporting_text: membrane-bound CHMP6-GFP colocalized to endosome-like organelles, including MVBs - reference_id: PMID:15511219 supporting_text: CHMP6 acts as an acceptor for ESCRT-II on endosomal membranes and regulates cargo sorting - reference_id: file:human/CHMP6/CHMP6-notes.md supporting_text: 'Accept as core: ESCRT III complex, ESCRT III complex assembly, endosome/late endosome/MVB membrane localization' - term: id: GO:0000815 label: ESCRT III complex evidence_type: IDA original_reference_id: PMID:24878737 qualifier: part_of review: summary: 'Supported core CHMP6 ESCRT-III complex membership: ESCRT III complex.' action: ACCEPT 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. supported_by: - reference_id: PMID:15511219 supporting_text: interacts directly with an ESCRT-II component EAP20 and regulates endosomal cargo sorting - reference_id: PMID:14519844 supporting_text: Each of the putative ESCRT-II components Eap45, Eap30, and Eap20 bound to each other, and to the ESCRT-III protein, CHMP6 - reference_id: UniProt:Q96FZ7 supporting_text: probably serves as an acceptor for the ESCRT-II complex on endosomal membranes - reference_id: file:human/CHMP6/CHMP6-notes.md supporting_text: CHMP6 is the human Vps20 ortholog and a core ESCRT-III pathway component. - term: id: GO:1903541 label: regulation of exosomal secretion evidence_type: IMP original_reference_id: PMID:22660413 qualifier: involved_in negated: true review: summary: Retain the existing NOT annotation for exosome secretion. action: ACCEPT reason: The GOA assertion is explicitly negated; the review should not convert this into a positive CHMP6 exosome-secretion function. supported_by: - reference_id: PMID:22660413 supporting_text: Syndecan-syntenin-ALIX regulates the biogenesis of exosomes - reference_id: file:human/CHMP6/CHMP6-notes.md supporting_text: The negated exosome secretion annotation should be retained as a supported NOT annotation rather than converted into a positive functional claim - term: id: GO:0016020 label: membrane evidence_type: HDA original_reference_id: PMID:19946888 qualifier: located_in review: summary: 'True but broad CHMP6 membrane location: membrane.' action: KEEP_AS_NON_CORE 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. supported_by: - reference_id: PMID:15511219 supporting_text: CHMP6 acts as an acceptor for ESCRT-II on endosomal membranes and regulates cargo sorting - reference_id: file:human/CHMP6/CHMP6-notes.md supporting_text: 'Accept as core: ESCRT III complex, ESCRT III complex assembly, endosome/late endosome/MVB membrane localization' - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:14519844 qualifier: enables review: summary: 'Generic protein binding is over-annotated for CHMP6: protein binding.' action: MARK_AS_OVER_ANNOTATED 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. supported_by: - reference_id: PMID:14519844 supporting_text: Each of the putative ESCRT-II components Eap45, Eap30, and Eap20 bound to each other, and to the ESCRT-III protein, CHMP6 - reference_id: PMID:18606141 supporting_text: solution structure of the VPS4A MIT domain in complex with its CHMP6166-181 binding site - reference_id: file:human/CHMP6/CHMP6-notes.md supporting_text: The interactions are real, but GO:0005515 erases the meaningful ESCRT-II, CHMP4, and VPS4 context. - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:14505570 qualifier: enables review: summary: 'Generic protein binding is over-annotated for CHMP6: protein binding.' action: MARK_AS_OVER_ANNOTATED 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. supported_by: - reference_id: PMID:14519844 supporting_text: Each of the putative ESCRT-II components Eap45, Eap30, and Eap20 bound to each other, and to the ESCRT-III protein, CHMP6 - reference_id: PMID:18606141 supporting_text: solution structure of the VPS4A MIT domain in complex with its CHMP6166-181 binding site - reference_id: file:human/CHMP6/CHMP6-notes.md supporting_text: The interactions are real, but GO:0005515 erases the meaningful ESCRT-II, CHMP4, and VPS4 context. - term: id: GO:0070062 label: extracellular exosome evidence_type: HDA original_reference_id: PMID:19056867 qualifier: located_in review: summary: 'Broad proteomics exosome detection is non-core for CHMP6: extracellular exosome.' action: KEEP_AS_NON_CORE 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. supported_by: - reference_id: PMID:19056867 supporting_text: Large-scale proteomics and phosphoproteomics of urinary exosomes - reference_id: PMID:20458337 supporting_text: MHC class II-associated proteins in B-cell exosomes - reference_id: file:human/CHMP6/CHMP6-notes.md supporting_text: 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 - term: id: GO:0070062 label: extracellular exosome evidence_type: HDA original_reference_id: PMID:20458337 qualifier: located_in review: summary: 'Broad proteomics exosome detection is non-core for CHMP6: extracellular exosome.' action: KEEP_AS_NON_CORE 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. supported_by: - reference_id: PMID:19056867 supporting_text: Large-scale proteomics and phosphoproteomics of urinary exosomes - reference_id: PMID:20458337 supporting_text: MHC class II-associated proteins in B-cell exosomes - reference_id: file:human/CHMP6/CHMP6-notes.md supporting_text: 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 - term: id: GO:0005829 label: cytosol evidence_type: TAS original_reference_id: Reactome:R-HSA-3159232 qualifier: located_in review: summary: 'True or plausible broad CHMP6 soluble pool/location: cytosol.' action: KEEP_AS_NON_CORE reason: CHMP6 cycles between soluble/inactive and membrane-associated ESCRT assemblies; cytosolic Reactome locations are pathway context, not the core proteostasis function. supported_by: - reference_id: PMID:17547705 supporting_text: full-length proteins does not - reference_id: file:human/CHMP6/CHMP6-notes.md supporting_text: 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 - term: id: GO:0005829 label: cytosol evidence_type: TAS original_reference_id: Reactome:R-HSA-917693 qualifier: located_in review: summary: 'True or plausible broad CHMP6 soluble pool/location: cytosol.' action: KEEP_AS_NON_CORE reason: CHMP6 cycles between soluble/inactive and membrane-associated ESCRT assemblies; cytosolic Reactome locations are pathway context, not the core proteostasis function. supported_by: - reference_id: PMID:17547705 supporting_text: full-length proteins does not - reference_id: file:human/CHMP6/CHMP6-notes.md supporting_text: 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 - term: id: GO:0005829 label: cytosol evidence_type: TAS original_reference_id: Reactome:R-HSA-917700 qualifier: located_in review: summary: 'True or plausible broad CHMP6 soluble pool/location: cytosol.' action: KEEP_AS_NON_CORE reason: CHMP6 cycles between soluble/inactive and membrane-associated ESCRT assemblies; cytosolic Reactome locations are pathway context, not the core proteostasis function. supported_by: - reference_id: PMID:17547705 supporting_text: full-length proteins does not - reference_id: file:human/CHMP6/CHMP6-notes.md supporting_text: 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 - term: id: GO:0005829 label: cytosol evidence_type: TAS original_reference_id: Reactome:R-HSA-9668389 qualifier: located_in review: summary: 'True or plausible broad CHMP6 soluble pool/location: cytosol.' action: KEEP_AS_NON_CORE reason: CHMP6 cycles between soluble/inactive and membrane-associated ESCRT assemblies; cytosolic Reactome locations are pathway context, not the core proteostasis function. supported_by: - reference_id: PMID:17547705 supporting_text: full-length proteins does not - reference_id: file:human/CHMP6/CHMP6-notes.md supporting_text: 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 - term: id: GO:0005829 label: cytosol evidence_type: TAS original_reference_id: Reactome:R-HSA-9668395 qualifier: located_in review: summary: 'True or plausible broad CHMP6 soluble pool/location: cytosol.' action: KEEP_AS_NON_CORE reason: CHMP6 cycles between soluble/inactive and membrane-associated ESCRT assemblies; cytosolic Reactome locations are pathway context, not the core proteostasis function. supported_by: - reference_id: PMID:17547705 supporting_text: full-length proteins does not - reference_id: file:human/CHMP6/CHMP6-notes.md supporting_text: 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 - term: id: GO:0005829 label: cytosol evidence_type: TAS original_reference_id: Reactome:R-HSA-9668398 qualifier: located_in review: summary: 'True or plausible broad CHMP6 soluble pool/location: cytosol.' action: KEEP_AS_NON_CORE reason: CHMP6 cycles between soluble/inactive and membrane-associated ESCRT assemblies; cytosolic Reactome locations are pathway context, not the core proteostasis function. supported_by: - reference_id: PMID:17547705 supporting_text: full-length proteins does not - reference_id: file:human/CHMP6/CHMP6-notes.md supporting_text: 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 - term: id: GO:0005829 label: cytosol evidence_type: TAS original_reference_id: Reactome:R-HSA-9668405 qualifier: located_in review: summary: 'True or plausible broad CHMP6 soluble pool/location: cytosol.' action: KEEP_AS_NON_CORE reason: CHMP6 cycles between soluble/inactive and membrane-associated ESCRT assemblies; cytosolic Reactome locations are pathway context, not the core proteostasis function. supported_by: - reference_id: PMID:17547705 supporting_text: full-length proteins does not - reference_id: file:human/CHMP6/CHMP6-notes.md supporting_text: 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 - term: id: GO:0005829 label: cytosol evidence_type: TAS original_reference_id: Reactome:R-HSA-9668415 qualifier: located_in review: summary: 'True or plausible broad CHMP6 soluble pool/location: cytosol.' action: KEEP_AS_NON_CORE reason: CHMP6 cycles between soluble/inactive and membrane-associated ESCRT assemblies; cytosolic Reactome locations are pathway context, not the core proteostasis function. supported_by: - reference_id: PMID:17547705 supporting_text: full-length proteins does not - reference_id: file:human/CHMP6/CHMP6-notes.md supporting_text: 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 - term: id: GO:0005829 label: cytosol evidence_type: TAS original_reference_id: Reactome:R-HSA-9668419 qualifier: located_in review: summary: 'True or plausible broad CHMP6 soluble pool/location: cytosol.' action: KEEP_AS_NON_CORE reason: CHMP6 cycles between soluble/inactive and membrane-associated ESCRT assemblies; cytosolic Reactome locations are pathway context, not the core proteostasis function. supported_by: - reference_id: PMID:17547705 supporting_text: full-length proteins does not - reference_id: file:human/CHMP6/CHMP6-notes.md supporting_text: 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 - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:21543490 qualifier: enables review: summary: 'Generic protein binding is over-annotated for CHMP6: protein binding.' action: MARK_AS_OVER_ANNOTATED 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. supported_by: - reference_id: PMID:14519844 supporting_text: Each of the putative ESCRT-II components Eap45, Eap30, and Eap20 bound to each other, and to the ESCRT-III protein, CHMP6 - reference_id: PMID:18606141 supporting_text: solution structure of the VPS4A MIT domain in complex with its CHMP6166-181 binding site - reference_id: file:human/CHMP6/CHMP6-notes.md supporting_text: The interactions are real, but GO:0005515 erases the meaningful ESCRT-II, CHMP4, and VPS4 context. - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:18606141 qualifier: enables review: summary: 'Generic protein binding is over-annotated for CHMP6: protein binding.' action: MARK_AS_OVER_ANNOTATED 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. supported_by: - reference_id: PMID:14519844 supporting_text: Each of the putative ESCRT-II components Eap45, Eap30, and Eap20 bound to each other, and to the ESCRT-III protein, CHMP6 - reference_id: PMID:18606141 supporting_text: solution structure of the VPS4A MIT domain in complex with its CHMP6166-181 binding site - reference_id: file:human/CHMP6/CHMP6-notes.md supporting_text: The interactions are real, but GO:0005515 erases the meaningful ESCRT-II, CHMP4, and VPS4 context. references: - id: GO_REF:0000002 title: Gene Ontology annotation through association of InterPro records with GO terms findings: [] - id: GO_REF:0000033 title: Annotation inferences using phylogenetic trees findings: [] - id: GO_REF:0000044 title: Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular Location vocabulary mapping, accompanied by conservative changes to GO terms applied by UniProt findings: [] - id: GO_REF:0000117 title: Electronic Gene Ontology annotations created by ARBA machine learning models findings: [] - id: PMID:14505570 title: The protein network of HIV budding. findings: [] - id: PMID:14519844 title: Divergent retroviral late-budding domains recruit vacuolar protein sorting factors by using alternative adaptor proteins. findings: [] - id: PMID:16505166 title: Recycling of ESCRTs by the AAA-ATPase Vps4 is regulated by a conserved VSL region in Vta1. findings: [] - id: PMID:16554368 title: The ESCRT-III subunit hVps24 is required for degradation but not silencing of the epidermal growth factor receptor. findings: [] - id: PMID:16730941 title: 'A systematic analysis of human CHMP protein interactions: additional MIT domain-containing proteins bind to multiple components of the human ESCRT III complex.' findings: [] - id: PMID:16856878 title: CHMP7, a novel ESCRT-III-related protein, associates with CHMP4b and functions in the endosomal sorting pathway. findings: [] - id: PMID:16973552 title: Human ESCRT-II complex and its role in human immunodeficiency virus type 1 release. findings: [] - id: PMID:17984323 title: Functional multivesicular bodies are required for autophagic clearance of protein aggregates associated with neurodegenerative disease. findings: [] - id: PMID:18606141 title: Two distinct modes of ESCRT-III recognition are required for VPS4 functions in lysosomal protein targeting and HIV-1 budding. findings: [] - id: PMID:19056867 title: Large-scale proteomics and phosphoproteomics of urinary exosomes. findings: [] - id: PMID:19234443 title: Membrane scission by the ESCRT-III complex. findings: [] - id: PMID:19946888 title: Defining the membrane proteome of NK cells. findings: [] - id: PMID:20458337 title: MHC class II-associated proteins in B-cell exosomes and potential functional implications for exosome biogenesis. findings: [] - id: PMID:20588296 title: 'Membrane budding and scission by the ESCRT machinery: it''s all in the neck.' findings: [] - id: PMID:20616062 title: Human ESCRT-III and VPS4 proteins are required for centrosome and spindle maintenance. findings: [] - id: PMID:21543490 title: Mechanism of inhibition of retrovirus release from cells by interferon-induced gene ISG15. findings: [] - id: PMID:22660413 title: Syndecan-syntenin-ALIX regulates the biogenesis of exosomes. findings: [] - id: PMID:24482116 title: ESCRT machinery is required for plasma membrane repair. findings: [] - id: PMID:24878737 title: Structure of cellular ESCRT-III spirals and their relationship to HIV budding. findings: [] - id: PMID:26040712 title: Spastin and ESCRT-III coordinate mitotic spindle disassembly and nuclear envelope sealing. findings: [] - id: PMID:26040713 title: ESCRT-III controls nuclear envelope reformation. findings: [] - id: PMID:32296183 title: A reference map of the human binary protein interactome. findings: [] - id: PMID:32814053 title: Interactome Mapping Provides a Network of Neurodegenerative Disease Proteins and Uncovers Widespread Protein Aggregation in Affected Brains. findings: [] - id: PMID:33961781 title: Dual proteome-scale networks reveal cell-specific remodeling of the human interactome. findings: [] - id: PMID:36107470 title: Comprehensive analysis of the human ESCRT-III-MIT domain interactome reveals new cofactors for cytokinetic abscission. findings: [] - id: Reactome:R-HSA-3159232 title: Recruitment Of HIV Virion Budding Machinery findings: [] - id: Reactome:R-HSA-917693 title: ESCRT Disassembly findings: [] - id: Reactome:R-HSA-917700 title: MVB Vesicle Formation findings: [] - id: Reactome:R-HSA-9668389 title: VPS4 binds ESCRT-III assemblies at nuclear envelope (NE) fenestrations findings: [] - id: Reactome:R-HSA-9668395 title: CHMP7 binds CC2D1B findings: [] - id: Reactome:R-HSA-9668398 title: CHMP7 binds CHMP4B, which recruits other subunits of the ESCRT-III complex findings: [] - id: Reactome:R-HSA-9668405 title: SPAST (spastin) binds the IST1 subunit of ESCRT-III at the sites of microtubule attachment to chromatin findings: [] - id: Reactome:R-HSA-9668415 title: VPS4 mediates disassembly of ESCRTIII subunits to promote sealing of holes in the nuclear envelope findings: [] - id: Reactome:R-HSA-9668419 title: SPAST (spastin) mediates the severing of microtubules at chromosome attachment sites findings: [] - id: UniProt:Q96FZ7 title: UniProtKB entry Q96FZ7 (CHMP6) findings: - statement: CHMP6 is a probable ESCRT-III component involved in MVB formation and cargo sorting and probably serves as an ESCRT-II acceptor on endosomal membranes. supporting_text: probably serves as an acceptor for the ESCRT-II complex on endosomal membranes - id: file:human/CHMP6/CHMP6-notes.md title: CHMP6 review notes findings: - statement: CHMP6 core function is ESCRT-II-to-ESCRT-III handoff and MVB cargo sorting rather than generic protein binding or broad ESCRT pleiotropy. supporting_text: CHMP6 is the human Vps20 ortholog and a core ESCRT-III pathway component. - id: PMID:15511219 title: Human CHMP6, a myristoylated ESCRT-III protein, interacts directly with an ESCRT-II component EAP20 and regulates endosomal cargo sorting. findings: - statement: CHMP6 is myristoylated, interacts with EAP20 and CHMP4b, localizes to endosomal/MVB membranes, and regulates cargo sorting. supporting_text: CHMP6 acts as an acceptor for ESCRT-II on endosomal membranes and regulates cargo sorting - id: PMID:17547705 title: Structure/function analysis of four core ESCRT-III proteins reveals common regulatory role for extreme C-terminal domain. findings: - statement: Core ESCRT-III proteins including hVps20/CHMP6 are autoinhibited and can assemble on endosomal membranes when the C-terminal inhibitory region is removed. supporting_text: 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 core_functions: - description: CHMP6 is a myristoylated Vps20/ESCRT-III component that links ESCRT-II to ESCRT-III on endosomal membranes. By binding ESCRT-II, CHMP4-family ESCRT-III subunits, and VPS4 through its MIM2 element, CHMP6 supports ESCRT-III assembly/remodeling, MVB formation and sorting of ubiquitinated/endocytosed membrane cargo, and downstream late-endosome-to-lysosome degradation of cargo such as EGFR and ferroportin. molecular_function: id: GO:0044877 label: protein-containing complex binding in_complex: id: GO:0000815 label: ESCRT III complex directly_involved_in: - id: GO:1904902 label: ESCRT III complex assembly - id: GO:0036258 label: multivesicular body assembly - id: GO:0071985 label: multivesicular body sorting pathway - id: GO:0043162 label: ubiquitin-dependent protein catabolic process via the multivesicular body sorting pathway - id: GO:1902774 label: late endosome to lysosome transport - id: GO:0090148 label: membrane fission - id: GO:0007175 label: negative regulation of epidermal growth factor-activated receptor activity locations: - id: GO:0010008 label: endosome membrane - id: GO:0031902 label: late endosome membrane - id: GO:0032585 label: multivesicular body membrane supported_by: - reference_id: PMID:15511219 supporting_text: CHMP6 acts as an acceptor for ESCRT-II on endosomal membranes and regulates cargo sorting - reference_id: PMID:15511219 supporting_text: Ubiquitinated proteins and endocytosed EGF continuously accumulated in CHMP6-GFP-expressing cells - reference_id: PMID:16973552 supporting_text: depletion of EAP20/ESCRT-II and CHMP6/ESCRT-III inhibited lysosomal targeting and downregulation of the epidermal growth factor receptor - reference_id: PMID:18606141 supporting_text: mutations in the CHMP6 MIM2 element that block VPS4A MIT binding also block ferroportin downregulation - reference_id: UniProt:Q96FZ7 supporting_text: probably serves as an acceptor for the ESCRT-II complex on endosomal membranes - reference_id: file:human/CHMP6/CHMP6-notes.md supporting_text: CHMP6 is the human Vps20 ortholog and a core ESCRT-III pathway component. - reference_id: PMID:15511219 supporting_text: interactions between CHMP6 and CHMP4b as well as between CHMP6 and EAP20 - reference_id: PMID:17547705 supporting_text: 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 - reference_id: PMID:18606141 supporting_text: both MIM1 and MIM2 interactions contribute in recruiting VPS4A to endosomal membranes - reference_id: file:human/CHMP6/CHMP6-notes.md supporting_text: CHMP6 has a conserved ESCRT-III autoinhibited/open behavior. - reference_id: PMID:15511219 supporting_text: Interactions of CHMP6 with another ESCRT-III component CHMP4b/Shax - reference_id: PMID:16973552 supporting_text: EAP20 bound the N-terminal half of CHMP6/ESCRT-III - reference_id: PMID:18606141 supporting_text: solution structure of the VPS4A MIT domain in complex with its CHMP6166-181 binding site - reference_id: file:human/CHMP6/CHMP6-notes.md supporting_text: protein-containing complex binding where it reflects ESCRT-II/ESCRT-III handoff rather than generic binding proposed_new_terms: [] suggested_questions: - question: Can endogenous CHMP6 depletion/rescue cleanly separate its ESCRT-II acceptor/nucleator role from later VPS4-mediated ESCRT-III recycling during MVB sorting? - question: 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? - question: Which autophagy and nuclear-envelope annotations are directly CHMP6-specific rather than inherited from broad ESCRT-III complex biology? suggested_experiments: - description: 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. - description: 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. - description: 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.