CHMP6

Existing Annotations Review

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.

📄 View Raw YAML

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.

Gene Description

Existing Annotations Review

Core Functions

References

Suggested Questions for Experts

Suggested Experiments

📚 Additional Documentation

Notes

CHMP6 notes

Review focus

Direct evidence

Annotation decisions

Literature access notes

Description cleanup note

Pn Notes

CHMP6 PN Consistency Notes

Source Files Checked

Deep Research Files

AIGR Review Snapshot

PN Consistency Summary

Full Consistency Review

PN Dossier Context

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

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

Projected GO annotations (3)

Note

📄 View Raw YAML