id: Q9NZZ3 gene_symbol: CHMP5 product_type: PROTEIN status: COMPLETE taxon: id: NCBITaxon:9606 label: Homo sapiens description: >- CHMP5 encodes a SNF7-family ESCRT-III-associated regulatory protein that links LIP5/VTA1 to VPS4-dependent ESCRT-III recycling during endosomal multivesicular body sorting. CHMP5 is primarily cytosolic but functions at endosomal ESCRT assemblies, where CHMP5-LIP5/VTA1 interactions help tune VPS4 activation/disassembly and support MVB cargo sorting and lysosomal degradation of membrane proteins such as EGFR. Broader ESCRT contexts including cytokinesis, nuclear-envelope sealing, plasma membrane repair, viral budding, and autophagy are biologically plausible but secondary; infection-specific evidence supports CHMP5 involvement in anti-Shigella autophagy rather than a general CHMP5-specific autophagosome maturation mechanism. alternative_products: - name: '1' id: Q9NZZ3-1 - name: '2' id: Q9NZZ3-2 sequence_note: VSP_042556 existing_annotations: - term: id: GO:0005635 label: nuclear envelope evidence_type: IBA original_reference_id: GO_REF:0000033 qualifier: is_active_in review: summary: 'Plausible non-core ESCRT nuclear-envelope context for CHMP5: nuclear envelope.' action: KEEP_AS_NON_CORE reason: Nuclear envelope sealing/reassembly is a supported ESCRT-III pathway context, but CHMP5-specific evidence is centered on MVB sorting and LIP5/VPS4-mediated ESCRT recycling. supported_by: - reference_id: PMID:26040712 supporting_text: ESCRT-III, VPS4 and spastin cooperate to coordinate nuclear envelope sealing and spindle disassembly - reference_id: PMID:26040713 supporting_text: ESCRT-III controls nuclear envelope reformation - reference_id: file:human/CHMP5/CHMP5-notes.md supporting_text: Secondary ESCRT contexts should generally be kept as non-core. - term: id: GO:0031468 label: nuclear membrane reassembly evidence_type: IBA original_reference_id: GO_REF:0000033 qualifier: involved_in review: summary: 'Plausible non-core ESCRT nuclear-envelope context for CHMP5: nuclear membrane reassembly.' action: KEEP_AS_NON_CORE reason: Nuclear envelope sealing/reassembly is a supported ESCRT-III pathway context, but CHMP5-specific evidence is centered on MVB sorting and LIP5/VPS4-mediated ESCRT recycling. supported_by: - reference_id: PMID:26040712 supporting_text: ESCRT-III, VPS4 and spastin cooperate to coordinate nuclear envelope sealing and spindle disassembly - reference_id: PMID:26040713 supporting_text: ESCRT-III controls nuclear envelope reformation - reference_id: file:human/CHMP5/CHMP5-notes.md supporting_text: Secondary ESCRT contexts should generally be kept as non-core. - term: id: GO:0000815 label: ESCRT III complex evidence_type: IBA original_reference_id: GO_REF:0000033 qualifier: part_of review: summary: 'Supported core CHMP5 ESCRT-III complex membership: ESCRT III complex.' action: ACCEPT reason: CHMP5 is an ESCRT-III-family component whose best-supported role is regulatory participation in ESCRT/MVB sorting and VPS4-LIP5-mediated ESCRT-III recycling. supported_by: - reference_id: UniProt:Q9NZZ3 supporting_text: Probable peripherally associated component of the endosomal sorting required for transport complex III (ESCRT-III) - reference_id: PMID:16730941 supporting_text: known components of the human ESCRT III complex - reference_id: PMID:23105106 supporting_text: the ESCRT-III and VPS4 ATPase complexes catalyze the membrane fission events associated with these processes - reference_id: file:human/CHMP5/CHMP5-notes.md supporting_text: CHMP5 (UniProt Q9NZZ3) is a SNF7/ESCRT-III family protein best treated as an ESCRT-III regulatory component for endosomal MVB sorting and VPS4/LIP5-mediated ESCRT-III recycling. - reference_id: PMID:18385515 supporting_text: LIP5 binds preferentially to soluble CHMP5 - reference_id: PMID:18385515 supporting_text: These studies point to a role for direct binding between LIP5 and ESCRT-III proteins - reference_id: PMID:23105106 supporting_text: promoting assembly of active VPS4 enzymes on the polymeric ESCRT-III substrate - reference_id: PMID:23105106 supporting_text: formation of stable VPS4 complexes with both LIP5 and CHMP5 requires LIP5 to bind both a MIM1-containing ESCRT-III protein and CHMP5 - reference_id: file:human/CHMP5/CHMP5-notes.md supporting_text: The mechanistic refinement is that CHMP5 binds LIP5/VTA1 and helps regulate VPS4 activation/disassembly of ESCRT-III rather than acting as a CHMP4/Snf7-like primary filament/scission subunit. - 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 the human CHMP5 annotation should use the direct MVB sorting term. action: MODIFY reason: CHMP5 is core to MVB sorting, but this vacuole-transport phrasing is less appropriate for a human protein than multivesicular body sorting pathway or the downstream late endosome-to-lysosome route. supported_by: - reference_id: UniProt:Q9NZZ3 supporting_text: involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs - reference_id: PMID:15644320 supporting_text: both LIP5 and CHMP5 function in MVB sorting - reference_id: PMID:15644320 supporting_text: Depletion of CHMP5 by siRNA does not affect the distribution or morphology of early endosomes, lysosomes, or Golgi but does result in reduced degradation of the EGFR - reference_id: file:human/CHMP5/CHMP5-notes.md supporting_text: 'Core: ESCRT-III complex membership, MVB sorting/assembly, ubiquitin-dependent cargo degradation through MVB sorting, ESCRT-III disassembly/recycling via LIP5/VTA1 and VPS4, and the endolysosomal degradation route that follows MVB sorting.' - reference_id: UniProt:Q9NZZ3 supporting_text: enabling degradation of membrane proteins, such as stimulated growth factor receptors - reference_id: PMID:15644320 supporting_text: reduced degradation of the EGFR similar to silencing of LIP5 - reference_id: PMID:17984323 supporting_text: Functional multivesicular bodies are required for autophagic clearance - reference_id: file:human/CHMP5/CHMP5-notes.md supporting_text: 'Proteostasis-network context: CHMP5 supports endolysosomal degradation through ESCRT/MVB sorting' 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 non-core ESCRT cell-cycle/centrosome context for CHMP5: kinetochore.' action: KEEP_AS_NON_CORE reason: CHMP5 and other ESCRT-III/VPS4 proteins have reported cell-cycle and abscission phenotypes, but these are secondary to the MVB sorting and ESCRT recycling function in the proteostasis review context. supported_by: - reference_id: PMID:20616062 supporting_text: depletion of VPS4A, VPS4B, or any of the 11 different human ESCRT-III (CHMP) proteins inhibited abscission - reference_id: PMID:20616062 supporting_text: producing multipolar spindles (most ESCRT-III/VPS4 proteins) or monopolar spindles (CHMP2A or CHMP5) - reference_id: PMID:20616062 supporting_text: ESCRT-III/VPS4 proteins function at centrosomes to help regulate their maintenance or proliferation and then at midbodies during abscission - reference_id: file:human/CHMP5/CHMP5-notes.md supporting_text: Secondary ESCRT contexts should generally be kept as non-core. - term: id: GO:0001778 label: plasma membrane repair evidence_type: IEA original_reference_id: GO_REF:0000117 qualifier: involved_in review: summary: Plausible non-core CHMP5 plasma membrane repair ESCRT context. action: KEEP_AS_NON_CORE reason: Plasma membrane repair is a valid ESCRT pathway output, but the available CHMP5-specific evidence does not make it the core CHMP5 function. supported_by: - reference_id: PMID:24482116 supporting_text: ESCRT proteins were recruited within seconds to plasma membrane wounds - reference_id: PMID:24482116 supporting_text: repair of certain wounds is ensured by ESCRT-mediated extracellular shedding of wounded portions - reference_id: file:human/CHMP5/CHMP5-notes.md supporting_text: Secondary ESCRT contexts should generally be kept as non-core. - term: id: GO:0005643 label: nuclear pore evidence_type: IEA original_reference_id: GO_REF:0000117 qualifier: part_of review: summary: 'Plausible non-core ESCRT nuclear-envelope context for CHMP5: nuclear pore.' action: KEEP_AS_NON_CORE reason: Nuclear envelope sealing/reassembly is a supported ESCRT-III pathway context, but CHMP5-specific evidence is centered on MVB sorting and LIP5/VPS4-mediated ESCRT recycling. supported_by: - reference_id: PMID:26040712 supporting_text: ESCRT-III, VPS4 and spastin cooperate to coordinate nuclear envelope sealing and spindle disassembly - reference_id: PMID:26040713 supporting_text: ESCRT-III controls nuclear envelope reformation - reference_id: file:human/CHMP5/CHMP5-notes.md supporting_text: Secondary ESCRT contexts should generally be kept as non-core. - 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 CHMP5 autophagy/endolysosomal context: lysosomal membrane.' action: KEEP_AS_NON_CORE reason: Functional MVB/ESCRT activity supports autophagic clearance and infection-specific CHMP5 evidence exists, but the cached annotations do not show CHMP5-specific autophagosome sealing/maturation as the core function. supported_by: - reference_id: PMID:17984323 supporting_text: Functional multivesicular bodies are required for autophagic clearance - reference_id: PMID:17984323 supporting_text: functional MVBs are required to prevent accumulation of abnormal proteins - reference_id: PMID:30061757 supporting_text: CHMP5-one of the IcsB targets and a component of the ESCRT-III complex-specifically affected S. flexneri escape from host autophagy. - reference_id: file:human/CHMP5/CHMP5-notes.md supporting_text: the cached CHMP5 GOA autophagy annotations mostly derive from ESCRT-complex context rather than CHMP5-specific autophagosome sealing assays - term: id: GO:0005828 label: kinetochore microtubule evidence_type: IEA original_reference_id: GO_REF:0000117 qualifier: located_in review: summary: 'Plausible non-core ESCRT cell-cycle/centrosome context for CHMP5: kinetochore microtubule.' action: KEEP_AS_NON_CORE reason: CHMP5 and other ESCRT-III/VPS4 proteins have reported cell-cycle and abscission phenotypes, but these are secondary to the MVB sorting and ESCRT recycling function in the proteostasis review context. supported_by: - reference_id: PMID:20616062 supporting_text: depletion of VPS4A, VPS4B, or any of the 11 different human ESCRT-III (CHMP) proteins inhibited abscission - reference_id: PMID:20616062 supporting_text: producing multipolar spindles (most ESCRT-III/VPS4 proteins) or monopolar spindles (CHMP2A or CHMP5) - reference_id: PMID:20616062 supporting_text: ESCRT-III/VPS4 proteins function at centrosomes to help regulate their maintenance or proliferation and then at midbodies during abscission - reference_id: file:human/CHMP5/CHMP5-notes.md supporting_text: Secondary ESCRT contexts should generally be kept as non-core. - term: id: GO:0005829 label: cytosol evidence_type: IEA original_reference_id: GO_REF:0000044 qualifier: located_in review: summary: 'True or plausible broad CHMP5 location: cytosol.' action: KEEP_AS_NON_CORE reason: CHMP5 is primarily cytosolic and can be detected in broad compartments, but broad locations do not define the core function. supported_by: - reference_id: UniProt:Q9NZZ3 supporting_text: Cytoplasm, cytosol - reference_id: PMID:15644320 supporting_text: We identify CHMP5 as a LIP5-binding protein and show that CHMP5 is primarily cytosolic. - reference_id: file:human/CHMP5/CHMP5-notes.md supporting_text: 'Non-core: cytosol/nucleus/exosome locations, midbody/cytokinesis, spindle/centrosome, nuclear envelope/pore reassembly, plasma membrane repair, infection/autophagy contexts, and viral budding.' - term: id: GO:0007034 label: vacuolar transport evidence_type: IEA original_reference_id: GO_REF:0000002 qualifier: involved_in review: summary: Vacuolar transport is too broad for CHMP5 and should be represented as MVB sorting. action: MODIFY reason: The conserved ESCRT biology is cargo sorting into MVBs followed by lysosomal delivery, not generic vacuolar transport. supported_by: - reference_id: UniProt:Q9NZZ3 supporting_text: involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs - reference_id: PMID:15644320 supporting_text: both LIP5 and CHMP5 function in MVB sorting - reference_id: PMID:15644320 supporting_text: Depletion of CHMP5 by siRNA does not affect the distribution or morphology of early endosomes, lysosomes, or Golgi but does result in reduced degradation of the EGFR - reference_id: file:human/CHMP5/CHMP5-notes.md supporting_text: 'Core: ESCRT-III complex membership, MVB sorting/assembly, ubiquitin-dependent cargo degradation through MVB sorting, ESCRT-III disassembly/recycling via LIP5/VTA1 and VPS4, and the endolysosomal degradation route that follows MVB sorting.' proposed_replacement_terms: - id: GO:0071985 label: multivesicular body sorting pathway - term: id: GO:0007080 label: mitotic metaphase chromosome alignment evidence_type: IEA original_reference_id: GO_REF:0000117 qualifier: involved_in review: summary: 'Plausible non-core ESCRT cell-cycle/centrosome context for CHMP5: mitotic metaphase chromosome alignment.' action: KEEP_AS_NON_CORE reason: CHMP5 and other ESCRT-III/VPS4 proteins have reported cell-cycle and abscission phenotypes, but these are secondary to the MVB sorting and ESCRT recycling function in the proteostasis review context. supported_by: - reference_id: PMID:20616062 supporting_text: depletion of VPS4A, VPS4B, or any of the 11 different human ESCRT-III (CHMP) proteins inhibited abscission - reference_id: PMID:20616062 supporting_text: producing multipolar spindles (most ESCRT-III/VPS4 proteins) or monopolar spindles (CHMP2A or CHMP5) - reference_id: PMID:20616062 supporting_text: ESCRT-III/VPS4 proteins function at centrosomes to help regulate their maintenance or proliferation and then at midbodies during abscission - reference_id: file:human/CHMP5/CHMP5-notes.md supporting_text: Secondary ESCRT contexts should generally be kept as non-core. - term: id: GO:0010008 label: endosome membrane evidence_type: IEA original_reference_id: GO_REF:0000044 qualifier: located_in review: summary: 'Supported CHMP5 endosomal/MVB membrane context: endosome membrane.' action: ACCEPT reason: CHMP5 is a peripheral ESCRT-III component that cycles between cytosol and endosomal ESCRT assemblies, so the endosome/MVB membrane context is relevant to the core MVB sorting function. supported_by: - reference_id: UniProt:Q9NZZ3 supporting_text: involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs - reference_id: PMID:15644320 supporting_text: both LIP5 and CHMP5 function in MVB sorting - reference_id: PMID:15644320 supporting_text: Depletion of CHMP5 by siRNA does not affect the distribution or morphology of early endosomes, lysosomes, or Golgi but does result in reduced degradation of the EGFR - reference_id: file:human/CHMP5/CHMP5-notes.md supporting_text: 'Core: ESCRT-III complex membership, MVB sorting/assembly, ubiquitin-dependent cargo degradation through MVB sorting, ESCRT-III disassembly/recycling via LIP5/VTA1 and VPS4, and the endolysosomal degradation route that follows MVB sorting.' - reference_id: UniProt:Q9NZZ3 supporting_text: Probable peripherally associated component of the endosomal sorting required for transport complex III (ESCRT-III) - reference_id: PMID:16730941 supporting_text: known components of the human ESCRT III complex - reference_id: PMID:23105106 supporting_text: the ESCRT-III and VPS4 ATPase complexes catalyze the membrane fission events associated with these processes - reference_id: file:human/CHMP5/CHMP5-notes.md supporting_text: CHMP5 (UniProt Q9NZZ3) is a SNF7/ESCRT-III family protein best treated as an ESCRT-III regulatory component for endosomal MVB sorting and VPS4/LIP5-mediated ESCRT-III recycling. - term: id: GO:0030496 label: midbody evidence_type: IEA original_reference_id: GO_REF:0000120 qualifier: located_in review: summary: 'Plausible non-core ESCRT cell-cycle/centrosome context for CHMP5: midbody.' action: KEEP_AS_NON_CORE reason: CHMP5 and other ESCRT-III/VPS4 proteins have reported cell-cycle and abscission phenotypes, but these are secondary to the MVB sorting and ESCRT recycling function in the proteostasis review context. supported_by: - reference_id: PMID:20616062 supporting_text: depletion of VPS4A, VPS4B, or any of the 11 different human ESCRT-III (CHMP) proteins inhibited abscission - reference_id: PMID:20616062 supporting_text: producing multipolar spindles (most ESCRT-III/VPS4 proteins) or monopolar spindles (CHMP2A or CHMP5) - reference_id: PMID:20616062 supporting_text: ESCRT-III/VPS4 proteins function at centrosomes to help regulate their maintenance or proliferation and then at midbodies during abscission - reference_id: file:human/CHMP5/CHMP5-notes.md supporting_text: Secondary ESCRT contexts should generally be kept as non-core. - term: id: GO:0031468 label: nuclear membrane reassembly evidence_type: IEA original_reference_id: GO_REF:0000117 qualifier: involved_in review: summary: 'Plausible non-core ESCRT nuclear-envelope context for CHMP5: nuclear membrane reassembly.' action: KEEP_AS_NON_CORE reason: Nuclear envelope sealing/reassembly is a supported ESCRT-III pathway context, but CHMP5-specific evidence is centered on MVB sorting and LIP5/VPS4-mediated ESCRT recycling. supported_by: - reference_id: PMID:26040712 supporting_text: ESCRT-III, VPS4 and spastin cooperate to coordinate nuclear envelope sealing and spindle disassembly - reference_id: PMID:26040713 supporting_text: ESCRT-III controls nuclear envelope reformation - reference_id: file:human/CHMP5/CHMP5-notes.md supporting_text: Secondary ESCRT contexts should generally be kept as non-core. - term: id: GO:0032585 label: multivesicular body membrane evidence_type: IEA original_reference_id: GO_REF:0000117 qualifier: located_in review: summary: 'Supported CHMP5 endosomal/MVB membrane context: multivesicular body membrane.' action: ACCEPT reason: CHMP5 is a peripheral ESCRT-III component that cycles between cytosol and endosomal ESCRT assemblies, so the endosome/MVB membrane context is relevant to the core MVB sorting function. supported_by: - reference_id: UniProt:Q9NZZ3 supporting_text: involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs - reference_id: PMID:15644320 supporting_text: both LIP5 and CHMP5 function in MVB sorting - reference_id: PMID:15644320 supporting_text: Depletion of CHMP5 by siRNA does not affect the distribution or morphology of early endosomes, lysosomes, or Golgi but does result in reduced degradation of the EGFR - reference_id: file:human/CHMP5/CHMP5-notes.md supporting_text: 'Core: ESCRT-III complex membership, MVB sorting/assembly, ubiquitin-dependent cargo degradation through MVB sorting, ESCRT-III disassembly/recycling via LIP5/VTA1 and VPS4, and the endolysosomal degradation route that follows MVB sorting.' - reference_id: UniProt:Q9NZZ3 supporting_text: Probable peripherally associated component of the endosomal sorting required for transport complex III (ESCRT-III) - reference_id: PMID:16730941 supporting_text: known components of the human ESCRT III complex - reference_id: PMID:23105106 supporting_text: the ESCRT-III and VPS4 ATPase complexes catalyze the membrane fission events associated with these processes - reference_id: file:human/CHMP5/CHMP5-notes.md supporting_text: CHMP5 (UniProt Q9NZZ3) is a SNF7/ESCRT-III family protein best treated as an ESCRT-III regulatory component for endosomal MVB sorting and VPS4/LIP5-mediated ESCRT-III recycling. - 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: 'Viral budding is not a core CHMP5 cellular function and is likely over-annotated here: viral budding via host ESCRT complex.' action: MARK_AS_OVER_ANNOTATED reason: The key CHMP5/LIP5 study found CHMP5 depletion increased infectious HIV-1 release and concluded that only LIP5 is required for HIV release, so viral-budding annotations should not be treated as CHMP5 core function. supported_by: - reference_id: PMID:15644320 supporting_text: CHMP5 depletion results in an increase in the release of infectious HIV-1 particles - reference_id: PMID:15644320 supporting_text: both LIP5 and CHMP5 function in MVB sorting, whereas only LIP5 is required for HIV release. - reference_id: file:human/CHMP5/CHMP5-notes.md supporting_text: 'Over-annotated: generic protein binding, cadherin binding, viral budding as a CHMP5 function, and LPS/MDP response terms inferred from induction or interaction context rather than a demonstrated CHMP5 response function.' - 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 CHMP5 MVB/endolysosomal sorting annotation: ubiquitin-dependent protein catabolic process via the multivesicular body sorting pathway.' action: ACCEPT reason: CHMP5 depletion impairs EGFR degradation and CHMP5-LIP5/VTA1-VPS4 biology places it in the ESCRT machinery required for MVB cargo sorting and downstream lysosomal degradation. supported_by: - reference_id: UniProt:Q9NZZ3 supporting_text: involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs - reference_id: PMID:15644320 supporting_text: both LIP5 and CHMP5 function in MVB sorting - reference_id: PMID:15644320 supporting_text: Depletion of CHMP5 by siRNA does not affect the distribution or morphology of early endosomes, lysosomes, or Golgi but does result in reduced degradation of the EGFR - reference_id: file:human/CHMP5/CHMP5-notes.md supporting_text: 'Core: ESCRT-III complex membership, MVB sorting/assembly, ubiquitin-dependent cargo degradation through MVB sorting, ESCRT-III disassembly/recycling via LIP5/VTA1 and VPS4, and the endolysosomal degradation route that follows MVB sorting.' - reference_id: UniProt:Q9NZZ3 supporting_text: enabling degradation of membrane proteins, such as stimulated growth factor receptors - reference_id: PMID:15644320 supporting_text: reduced degradation of the EGFR similar to silencing of LIP5 - reference_id: PMID:17984323 supporting_text: Functional multivesicular bodies are required for autophagic clearance - reference_id: file:human/CHMP5/CHMP5-notes.md supporting_text: 'Proteostasis-network context: CHMP5 supports endolysosomal degradation through ESCRT/MVB sorting' - term: id: GO:0046761 label: viral budding from plasma membrane evidence_type: IEA original_reference_id: GO_REF:0000117 qualifier: involved_in review: summary: 'Viral budding is not a core CHMP5 cellular function and is likely over-annotated here: viral budding from plasma membrane.' action: MARK_AS_OVER_ANNOTATED reason: The key CHMP5/LIP5 study found CHMP5 depletion increased infectious HIV-1 release and concluded that only LIP5 is required for HIV release, so viral-budding annotations should not be treated as CHMP5 core function. supported_by: - reference_id: PMID:15644320 supporting_text: CHMP5 depletion results in an increase in the release of infectious HIV-1 particles - reference_id: PMID:15644320 supporting_text: both LIP5 and CHMP5 function in MVB sorting, whereas only LIP5 is required for HIV release. - reference_id: file:human/CHMP5/CHMP5-notes.md supporting_text: 'Over-annotated: generic protein binding, cadherin binding, viral budding as a CHMP5 function, and LPS/MDP response terms inferred from induction or interaction context rather than a demonstrated CHMP5 response function.' - term: id: GO:0061952 label: midbody abscission evidence_type: IEA original_reference_id: GO_REF:0000117 qualifier: involved_in review: summary: 'Plausible non-core ESCRT cell-cycle/centrosome context for CHMP5: midbody abscission.' action: KEEP_AS_NON_CORE reason: CHMP5 and other ESCRT-III/VPS4 proteins have reported cell-cycle and abscission phenotypes, but these are secondary to the MVB sorting and ESCRT recycling function in the proteostasis review context. supported_by: - reference_id: PMID:20616062 supporting_text: depletion of VPS4A, VPS4B, or any of the 11 different human ESCRT-III (CHMP) proteins inhibited abscission - reference_id: PMID:20616062 supporting_text: producing multipolar spindles (most ESCRT-III/VPS4 proteins) or monopolar spindles (CHMP2A or CHMP5) - reference_id: PMID:20616062 supporting_text: ESCRT-III/VPS4 proteins function at centrosomes to help regulate their maintenance or proliferation and then at midbodies during abscission - reference_id: file:human/CHMP5/CHMP5-notes.md supporting_text: Secondary ESCRT contexts should generally be kept as non-core. - 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 CHMP5 MVB/endolysosomal sorting annotation: multivesicular body sorting pathway.' action: ACCEPT reason: CHMP5 depletion impairs EGFR degradation and CHMP5-LIP5/VTA1-VPS4 biology places it in the ESCRT machinery required for MVB cargo sorting and downstream lysosomal degradation. supported_by: - reference_id: UniProt:Q9NZZ3 supporting_text: involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs - reference_id: PMID:15644320 supporting_text: both LIP5 and CHMP5 function in MVB sorting - reference_id: PMID:15644320 supporting_text: Depletion of CHMP5 by siRNA does not affect the distribution or morphology of early endosomes, lysosomes, or Golgi but does result in reduced degradation of the EGFR - reference_id: file:human/CHMP5/CHMP5-notes.md supporting_text: 'Core: ESCRT-III complex membership, MVB sorting/assembly, ubiquitin-dependent cargo degradation through MVB sorting, ESCRT-III disassembly/recycling via LIP5/VTA1 and VPS4, and the endolysosomal degradation route that follows MVB sorting.' - reference_id: UniProt:Q9NZZ3 supporting_text: enabling degradation of membrane proteins, such as stimulated growth factor receptors - reference_id: PMID:15644320 supporting_text: reduced degradation of the EGFR similar to silencing of LIP5 - reference_id: PMID:17984323 supporting_text: Functional multivesicular bodies are required for autophagic clearance - reference_id: file:human/CHMP5/CHMP5-notes.md supporting_text: 'Proteostasis-network context: CHMP5 supports endolysosomal degradation through ESCRT/MVB sorting' - 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 CHMP5 autophagy/endolysosomal context: autophagosome maturation.' action: KEEP_AS_NON_CORE reason: Functional MVB/ESCRT activity supports autophagic clearance and infection-specific CHMP5 evidence exists, but the cached annotations do not show CHMP5-specific autophagosome sealing/maturation as the core function. supported_by: - reference_id: PMID:17984323 supporting_text: Functional multivesicular bodies are required for autophagic clearance - reference_id: PMID:17984323 supporting_text: functional MVBs are required to prevent accumulation of abnormal proteins - reference_id: PMID:30061757 supporting_text: CHMP5-one of the IcsB targets and a component of the ESCRT-III complex-specifically affected S. flexneri escape from host autophagy. - reference_id: file:human/CHMP5/CHMP5-notes.md supporting_text: the cached CHMP5 GOA autophagy annotations mostly derive from ESCRT-complex context rather than CHMP5-specific autophagosome sealing assays - term: id: GO:1901673 label: regulation of mitotic spindle assembly evidence_type: IEA original_reference_id: GO_REF:0000117 qualifier: involved_in review: summary: 'Plausible non-core ESCRT cell-cycle/centrosome context for CHMP5: regulation of mitotic spindle assembly.' action: KEEP_AS_NON_CORE reason: CHMP5 and other ESCRT-III/VPS4 proteins have reported cell-cycle and abscission phenotypes, but these are secondary to the MVB sorting and ESCRT recycling function in the proteostasis review context. supported_by: - reference_id: PMID:20616062 supporting_text: depletion of VPS4A, VPS4B, or any of the 11 different human ESCRT-III (CHMP) proteins inhibited abscission - reference_id: PMID:20616062 supporting_text: producing multipolar spindles (most ESCRT-III/VPS4 proteins) or monopolar spindles (CHMP2A or CHMP5) - reference_id: PMID:20616062 supporting_text: ESCRT-III/VPS4 proteins function at centrosomes to help regulate their maintenance or proliferation and then at midbodies during abscission - reference_id: file:human/CHMP5/CHMP5-notes.md supporting_text: Secondary ESCRT contexts should generally be kept as non-core. - 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 CHMP5 endolysosomal degradation route annotation. action: ACCEPT reason: CHMP5-mediated MVB sorting supports delivery of cargo such as EGFR into the degradative endolysosomal route; this term is an appropriate pathway endpoint for the MVB sorting function. supported_by: - reference_id: UniProt:Q9NZZ3 supporting_text: involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs - reference_id: PMID:15644320 supporting_text: both LIP5 and CHMP5 function in MVB sorting - reference_id: PMID:15644320 supporting_text: Depletion of CHMP5 by siRNA does not affect the distribution or morphology of early endosomes, lysosomes, or Golgi but does result in reduced degradation of the EGFR - reference_id: file:human/CHMP5/CHMP5-notes.md supporting_text: 'Core: ESCRT-III complex membership, MVB sorting/assembly, ubiquitin-dependent cargo degradation through MVB sorting, ESCRT-III disassembly/recycling via LIP5/VTA1 and VPS4, and the endolysosomal degradation route that follows MVB sorting.' - reference_id: UniProt:Q9NZZ3 supporting_text: enabling degradation of membrane proteins, such as stimulated growth factor receptors - reference_id: PMID:15644320 supporting_text: reduced degradation of the EGFR similar to silencing of LIP5 - reference_id: PMID:17984323 supporting_text: Functional multivesicular bodies are required for autophagic clearance - reference_id: file:human/CHMP5/CHMP5-notes.md supporting_text: 'Proteostasis-network context: CHMP5 supports endolysosomal degradation through ESCRT/MVB sorting' - 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 CHMP5 autophagy/endolysosomal context: amphisome membrane.' action: KEEP_AS_NON_CORE reason: Functional MVB/ESCRT activity supports autophagic clearance and infection-specific CHMP5 evidence exists, but the cached annotations do not show CHMP5-specific autophagosome sealing/maturation as the core function. supported_by: - reference_id: PMID:17984323 supporting_text: Functional multivesicular bodies are required for autophagic clearance - reference_id: PMID:17984323 supporting_text: functional MVBs are required to prevent accumulation of abnormal proteins - reference_id: PMID:30061757 supporting_text: CHMP5-one of the IcsB targets and a component of the ESCRT-III complex-specifically affected S. flexneri escape from host autophagy. - reference_id: file:human/CHMP5/CHMP5-notes.md supporting_text: the cached CHMP5 GOA autophagy annotations mostly derive from ESCRT-complex context rather than CHMP5-specific autophagosome sealing assays - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:16730941 qualifier: enables review: summary: Generic protein binding does not capture the specific CHMP5/LIP5/VPS4-ESCRT regulatory mechanism. action: MARK_AS_OVER_ANNOTATED reason: The interactions with LIP5/VTA1 and other ESCRT-associated proteins are biologically meaningful, but the GO term protein binding is too generic to capture CHMP5 function. supported_by: - reference_id: PMID:15644320 supporting_text: We identify CHMP5 as a LIP5-binding protein and show that CHMP5 is primarily cytosolic. - reference_id: PMID:18385515 supporting_text: LIP5 binds preferentially to soluble CHMP5 - reference_id: PMID:23105106 supporting_text: the second LIP5 MIT module binds with unusually high affinity to a novel MIM element within the ESCRT-III protein CHMP5 - reference_id: file:human/CHMP5/CHMP5-notes.md supporting_text: 'Over-annotated: generic protein binding, cadherin binding, viral budding as a CHMP5 function, and LPS/MDP response terms inferred from induction or interaction context rather than a demonstrated CHMP5 response function.' - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:17711858 qualifier: enables review: summary: Generic protein binding does not capture the specific CHMP5/LIP5/VPS4-ESCRT regulatory mechanism. action: MARK_AS_OVER_ANNOTATED reason: The interactions with LIP5/VTA1 and other ESCRT-associated proteins are biologically meaningful, but the GO term protein binding is too generic to capture CHMP5 function. supported_by: - reference_id: PMID:15644320 supporting_text: We identify CHMP5 as a LIP5-binding protein and show that CHMP5 is primarily cytosolic. - reference_id: PMID:18385515 supporting_text: LIP5 binds preferentially to soluble CHMP5 - reference_id: PMID:23105106 supporting_text: the second LIP5 MIT module binds with unusually high affinity to a novel MIM element within the ESCRT-III protein CHMP5 - reference_id: file:human/CHMP5/CHMP5-notes.md supporting_text: 'Over-annotated: generic protein binding, cadherin binding, viral budding as a CHMP5 function, and LPS/MDP response terms inferred from induction or interaction context rather than a demonstrated CHMP5 response function.' - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:21988832 qualifier: enables review: summary: Generic protein binding does not capture the specific CHMP5/LIP5/VPS4-ESCRT regulatory mechanism. action: MARK_AS_OVER_ANNOTATED reason: The interactions with LIP5/VTA1 and other ESCRT-associated proteins are biologically meaningful, but the GO term protein binding is too generic to capture CHMP5 function. supported_by: - reference_id: PMID:15644320 supporting_text: We identify CHMP5 as a LIP5-binding protein and show that CHMP5 is primarily cytosolic. - reference_id: PMID:18385515 supporting_text: LIP5 binds preferentially to soluble CHMP5 - reference_id: PMID:23105106 supporting_text: the second LIP5 MIT module binds with unusually high affinity to a novel MIM element within the ESCRT-III protein CHMP5 - reference_id: file:human/CHMP5/CHMP5-notes.md supporting_text: 'Over-annotated: generic protein binding, cadherin binding, viral budding as a CHMP5 function, and LPS/MDP response terms inferred from induction or interaction context rather than a demonstrated CHMP5 response function.' - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:25416956 qualifier: enables review: summary: Generic protein binding does not capture the specific CHMP5/LIP5/VPS4-ESCRT regulatory mechanism. action: MARK_AS_OVER_ANNOTATED reason: The interactions with LIP5/VTA1 and other ESCRT-associated proteins are biologically meaningful, but the GO term protein binding is too generic to capture CHMP5 function. supported_by: - reference_id: PMID:15644320 supporting_text: We identify CHMP5 as a LIP5-binding protein and show that CHMP5 is primarily cytosolic. - reference_id: PMID:18385515 supporting_text: LIP5 binds preferentially to soluble CHMP5 - reference_id: PMID:23105106 supporting_text: the second LIP5 MIT module binds with unusually high affinity to a novel MIM element within the ESCRT-III protein CHMP5 - reference_id: file:human/CHMP5/CHMP5-notes.md supporting_text: 'Over-annotated: generic protein binding, cadherin binding, viral budding as a CHMP5 function, and LPS/MDP response terms inferred from induction or interaction context rather than a demonstrated CHMP5 response function.' - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:26496610 qualifier: enables review: summary: Generic protein binding does not capture the specific CHMP5/LIP5/VPS4-ESCRT regulatory mechanism. action: MARK_AS_OVER_ANNOTATED reason: The interactions with LIP5/VTA1 and other ESCRT-associated proteins are biologically meaningful, but the GO term protein binding is too generic to capture CHMP5 function. supported_by: - reference_id: PMID:15644320 supporting_text: We identify CHMP5 as a LIP5-binding protein and show that CHMP5 is primarily cytosolic. - reference_id: PMID:18385515 supporting_text: LIP5 binds preferentially to soluble CHMP5 - reference_id: PMID:23105106 supporting_text: the second LIP5 MIT module binds with unusually high affinity to a novel MIM element within the ESCRT-III protein CHMP5 - reference_id: file:human/CHMP5/CHMP5-notes.md supporting_text: 'Over-annotated: generic protein binding, cadherin binding, viral budding as a CHMP5 function, and LPS/MDP response terms inferred from induction or interaction context rather than a demonstrated CHMP5 response function.' - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:27812135 qualifier: enables review: summary: Generic protein binding does not capture the specific CHMP5/LIP5/VPS4-ESCRT regulatory mechanism. action: MARK_AS_OVER_ANNOTATED reason: The NOD2 interaction is experimentally supported, but generic protein binding is uninformative and the NOD2 study does not make this a core CHMP5 molecular function. supported_by: - reference_id: PMID:27812135 supporting_text: The primary interaction was confirmed by coimmunoprecipitation and/or bioluminescence resonance energy transfer (BRET) experiments for 11 of these proteins - reference_id: PMID:27812135 supporting_text: CHMP5ESCRTIII proteins are required for late MVB formation and their fusion with the lysosome - reference_id: file:human/CHMP5/CHMP5-notes.md supporting_text: The NOD2/LPS/MDP annotations are not core CHMP5 function. - reference_id: file:human/CHMP5/CHMP5-notes.md supporting_text: the study itself says these new interacting proteins did not appear to be major NOD2-dependent NF-kappaB regulators in the assay - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:28514442 qualifier: enables review: summary: Generic protein binding does not capture the specific CHMP5/LIP5/VPS4-ESCRT regulatory mechanism. action: MARK_AS_OVER_ANNOTATED reason: The interactions with LIP5/VTA1 and other ESCRT-associated proteins are biologically meaningful, but the GO term protein binding is too generic to capture CHMP5 function. supported_by: - reference_id: PMID:15644320 supporting_text: We identify CHMP5 as a LIP5-binding protein and show that CHMP5 is primarily cytosolic. - reference_id: PMID:18385515 supporting_text: LIP5 binds preferentially to soluble CHMP5 - reference_id: PMID:23105106 supporting_text: the second LIP5 MIT module binds with unusually high affinity to a novel MIM element within the ESCRT-III protein CHMP5 - reference_id: file:human/CHMP5/CHMP5-notes.md supporting_text: 'Over-annotated: generic protein binding, cadherin binding, viral budding as a CHMP5 function, and LPS/MDP response terms inferred from induction or interaction context rather than a demonstrated CHMP5 response function.' - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:32296183 qualifier: enables review: summary: Generic protein binding does not capture the specific CHMP5/LIP5/VPS4-ESCRT regulatory mechanism. action: MARK_AS_OVER_ANNOTATED reason: The interactions with LIP5/VTA1 and other ESCRT-associated proteins are biologically meaningful, but the GO term protein binding is too generic to capture CHMP5 function. supported_by: - reference_id: PMID:15644320 supporting_text: We identify CHMP5 as a LIP5-binding protein and show that CHMP5 is primarily cytosolic. - reference_id: PMID:18385515 supporting_text: LIP5 binds preferentially to soluble CHMP5 - reference_id: PMID:23105106 supporting_text: the second LIP5 MIT module binds with unusually high affinity to a novel MIM element within the ESCRT-III protein CHMP5 - reference_id: file:human/CHMP5/CHMP5-notes.md supporting_text: 'Over-annotated: generic protein binding, cadherin binding, viral budding as a CHMP5 function, and LPS/MDP response terms inferred from induction or interaction context rather than a demonstrated CHMP5 response function.' - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:33961781 qualifier: enables review: summary: Generic protein binding does not capture the specific CHMP5/LIP5/VPS4-ESCRT regulatory mechanism. action: MARK_AS_OVER_ANNOTATED reason: The interactions with LIP5/VTA1 and other ESCRT-associated proteins are biologically meaningful, but the GO term protein binding is too generic to capture CHMP5 function. supported_by: - reference_id: PMID:15644320 supporting_text: We identify CHMP5 as a LIP5-binding protein and show that CHMP5 is primarily cytosolic. - reference_id: PMID:18385515 supporting_text: LIP5 binds preferentially to soluble CHMP5 - reference_id: PMID:23105106 supporting_text: the second LIP5 MIT module binds with unusually high affinity to a novel MIM element within the ESCRT-III protein CHMP5 - reference_id: file:human/CHMP5/CHMP5-notes.md supporting_text: 'Over-annotated: generic protein binding, cadherin binding, viral budding as a CHMP5 function, and LPS/MDP response terms inferred from induction or interaction context rather than a demonstrated CHMP5 response function.' - term: id: GO:0005634 label: nucleus evidence_type: IEA original_reference_id: GO_REF:0000107 qualifier: located_in review: summary: 'True or plausible broad CHMP5 location: nucleus.' action: KEEP_AS_NON_CORE reason: CHMP5 is primarily cytosolic and can be detected in broad compartments, but broad locations do not define the core function. supported_by: - reference_id: UniProt:Q9NZZ3 supporting_text: Cytoplasm, cytosol - reference_id: PMID:15644320 supporting_text: We identify CHMP5 as a LIP5-binding protein and show that CHMP5 is primarily cytosolic. - reference_id: file:human/CHMP5/CHMP5-notes.md supporting_text: 'Non-core: cytosol/nucleus/exosome locations, midbody/cytokinesis, spindle/centrosome, nuclear envelope/pore reassembly, plasma membrane repair, infection/autophagy contexts, and viral budding.' - term: id: GO:0005829 label: cytosol evidence_type: IDA original_reference_id: GO_REF:0000052 qualifier: located_in review: summary: 'True or plausible broad CHMP5 location: cytosol.' action: KEEP_AS_NON_CORE reason: CHMP5 is primarily cytosolic and can be detected in broad compartments, but broad locations do not define the core function. supported_by: - reference_id: UniProt:Q9NZZ3 supporting_text: Cytoplasm, cytosol - reference_id: PMID:15644320 supporting_text: We identify CHMP5 as a LIP5-binding protein and show that CHMP5 is primarily cytosolic. - reference_id: file:human/CHMP5/CHMP5-notes.md supporting_text: 'Non-core: cytosol/nucleus/exosome locations, midbody/cytokinesis, spindle/centrosome, nuclear envelope/pore reassembly, plasma membrane repair, infection/autophagy contexts, and viral budding.' - term: id: GO:0015630 label: microtubule cytoskeleton evidence_type: IDA original_reference_id: GO_REF:0000052 qualifier: located_in review: summary: 'Plausible non-core ESCRT cell-cycle/centrosome context for CHMP5: microtubule cytoskeleton.' action: KEEP_AS_NON_CORE reason: CHMP5 and other ESCRT-III/VPS4 proteins have reported cell-cycle and abscission phenotypes, but these are secondary to the MVB sorting and ESCRT recycling function in the proteostasis review context. supported_by: - reference_id: PMID:20616062 supporting_text: depletion of VPS4A, VPS4B, or any of the 11 different human ESCRT-III (CHMP) proteins inhibited abscission - reference_id: PMID:20616062 supporting_text: producing multipolar spindles (most ESCRT-III/VPS4 proteins) or monopolar spindles (CHMP2A or CHMP5) - reference_id: PMID:20616062 supporting_text: ESCRT-III/VPS4 proteins function at centrosomes to help regulate their maintenance or proliferation and then at midbodies during abscission - reference_id: file:human/CHMP5/CHMP5-notes.md supporting_text: Secondary ESCRT contexts should generally be kept as non-core. - term: id: GO:0030496 label: midbody evidence_type: IDA original_reference_id: GO_REF:0000052 qualifier: located_in review: summary: 'Plausible non-core ESCRT cell-cycle/centrosome context for CHMP5: midbody.' action: KEEP_AS_NON_CORE reason: CHMP5 and other ESCRT-III/VPS4 proteins have reported cell-cycle and abscission phenotypes, but these are secondary to the MVB sorting and ESCRT recycling function in the proteostasis review context. supported_by: - reference_id: PMID:20616062 supporting_text: depletion of VPS4A, VPS4B, or any of the 11 different human ESCRT-III (CHMP) proteins inhibited abscission - reference_id: PMID:20616062 supporting_text: producing multipolar spindles (most ESCRT-III/VPS4 proteins) or monopolar spindles (CHMP2A or CHMP5) - reference_id: PMID:20616062 supporting_text: ESCRT-III/VPS4 proteins function at centrosomes to help regulate their maintenance or proliferation and then at midbodies during abscission - reference_id: file:human/CHMP5/CHMP5-notes.md supporting_text: Secondary ESCRT contexts should generally be kept as non-core. - 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 CHMP5 autophagy/endolysosomal context: autophagosome membrane.' action: KEEP_AS_NON_CORE reason: Functional MVB/ESCRT activity supports autophagic clearance and infection-specific CHMP5 evidence exists, but the cached annotations do not show CHMP5-specific autophagosome sealing/maturation as the core function. supported_by: - reference_id: PMID:17984323 supporting_text: Functional multivesicular bodies are required for autophagic clearance - reference_id: PMID:17984323 supporting_text: functional MVBs are required to prevent accumulation of abnormal proteins - reference_id: PMID:30061757 supporting_text: CHMP5-one of the IcsB targets and a component of the ESCRT-III complex-specifically affected S. flexneri escape from host autophagy. - reference_id: file:human/CHMP5/CHMP5-notes.md supporting_text: the cached CHMP5 GOA autophagy annotations mostly derive from ESCRT-complex context rather than CHMP5-specific autophagosome sealing assays - term: id: GO:0000776 label: kinetochore evidence_type: IDA original_reference_id: PMID:26040712 qualifier: located_in review: summary: 'Plausible non-core ESCRT cell-cycle/centrosome context for CHMP5: kinetochore.' action: KEEP_AS_NON_CORE reason: CHMP5 and other ESCRT-III/VPS4 proteins have reported cell-cycle and abscission phenotypes, but these are secondary to the MVB sorting and ESCRT recycling function in the proteostasis review context. supported_by: - reference_id: PMID:20616062 supporting_text: depletion of VPS4A, VPS4B, or any of the 11 different human ESCRT-III (CHMP) proteins inhibited abscission - reference_id: PMID:20616062 supporting_text: producing multipolar spindles (most ESCRT-III/VPS4 proteins) or monopolar spindles (CHMP2A or CHMP5) - reference_id: PMID:20616062 supporting_text: ESCRT-III/VPS4 proteins function at centrosomes to help regulate their maintenance or proliferation and then at midbodies during abscission - reference_id: file:human/CHMP5/CHMP5-notes.md supporting_text: Secondary ESCRT contexts should generally be kept as non-core. - term: id: GO:0000815 label: ESCRT III complex evidence_type: NAS original_reference_id: PMID:36107470 qualifier: part_of review: summary: 'Supported core CHMP5 ESCRT-III complex membership: ESCRT III complex.' action: ACCEPT reason: CHMP5 is an ESCRT-III-family component whose best-supported role is regulatory participation in ESCRT/MVB sorting and VPS4-LIP5-mediated ESCRT-III recycling. supported_by: - reference_id: UniProt:Q9NZZ3 supporting_text: Probable peripherally associated component of the endosomal sorting required for transport complex III (ESCRT-III) - reference_id: PMID:16730941 supporting_text: known components of the human ESCRT III complex - reference_id: PMID:23105106 supporting_text: the ESCRT-III and VPS4 ATPase complexes catalyze the membrane fission events associated with these processes - reference_id: file:human/CHMP5/CHMP5-notes.md supporting_text: CHMP5 (UniProt Q9NZZ3) is a SNF7/ESCRT-III family protein best treated as an ESCRT-III regulatory component for endosomal MVB sorting and VPS4/LIP5-mediated ESCRT-III recycling. - reference_id: PMID:18385515 supporting_text: LIP5 binds preferentially to soluble CHMP5 - reference_id: PMID:18385515 supporting_text: These studies point to a role for direct binding between LIP5 and ESCRT-III proteins - reference_id: PMID:23105106 supporting_text: promoting assembly of active VPS4 enzymes on the polymeric ESCRT-III substrate - reference_id: PMID:23105106 supporting_text: formation of stable VPS4 complexes with both LIP5 and CHMP5 requires LIP5 to bind both a MIM1-containing ESCRT-III protein and CHMP5 - reference_id: file:human/CHMP5/CHMP5-notes.md supporting_text: The mechanistic refinement is that CHMP5 binds LIP5/VTA1 and helps regulate VPS4 activation/disassembly of ESCRT-III rather than acting as a CHMP4/Snf7-like primary filament/scission subunit. - term: id: GO:0001778 label: plasma membrane repair evidence_type: IDA original_reference_id: PMID:24482116 qualifier: involved_in review: summary: Plausible non-core CHMP5 plasma membrane repair ESCRT context. action: KEEP_AS_NON_CORE reason: Plasma membrane repair is a valid ESCRT pathway output, but the available CHMP5-specific evidence does not make it the core CHMP5 function. supported_by: - reference_id: PMID:24482116 supporting_text: ESCRT proteins were recruited within seconds to plasma membrane wounds - reference_id: PMID:24482116 supporting_text: repair of certain wounds is ensured by ESCRT-mediated extracellular shedding of wounded portions - reference_id: file:human/CHMP5/CHMP5-notes.md supporting_text: Secondary ESCRT contexts should generally be kept as non-core. - term: id: GO:0005643 label: nuclear pore evidence_type: IDA original_reference_id: PMID:26040713 qualifier: part_of review: summary: 'Plausible non-core ESCRT nuclear-envelope context for CHMP5: nuclear pore.' action: KEEP_AS_NON_CORE reason: Nuclear envelope sealing/reassembly is a supported ESCRT-III pathway context, but CHMP5-specific evidence is centered on MVB sorting and LIP5/VPS4-mediated ESCRT recycling. supported_by: - reference_id: PMID:26040712 supporting_text: ESCRT-III, VPS4 and spastin cooperate to coordinate nuclear envelope sealing and spindle disassembly - reference_id: PMID:26040713 supporting_text: ESCRT-III controls nuclear envelope reformation - reference_id: file:human/CHMP5/CHMP5-notes.md supporting_text: Secondary ESCRT contexts should generally be kept as non-core. - 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 CHMP5 autophagy/endolysosomal context: lysosomal membrane.' action: KEEP_AS_NON_CORE reason: Functional MVB/ESCRT activity supports autophagic clearance and infection-specific CHMP5 evidence exists, but the cached annotations do not show CHMP5-specific autophagosome sealing/maturation as the core function. supported_by: - reference_id: PMID:17984323 supporting_text: Functional multivesicular bodies are required for autophagic clearance - reference_id: PMID:17984323 supporting_text: functional MVBs are required to prevent accumulation of abnormal proteins - reference_id: PMID:30061757 supporting_text: CHMP5-one of the IcsB targets and a component of the ESCRT-III complex-specifically affected S. flexneri escape from host autophagy. - reference_id: file:human/CHMP5/CHMP5-notes.md supporting_text: the cached CHMP5 GOA autophagy annotations mostly derive from ESCRT-complex context rather than CHMP5-specific autophagosome sealing assays - term: id: GO:0005828 label: kinetochore microtubule evidence_type: IDA original_reference_id: PMID:26040712 qualifier: located_in review: summary: 'Plausible non-core ESCRT cell-cycle/centrosome context for CHMP5: kinetochore microtubule.' action: KEEP_AS_NON_CORE reason: CHMP5 and other ESCRT-III/VPS4 proteins have reported cell-cycle and abscission phenotypes, but these are secondary to the MVB sorting and ESCRT recycling function in the proteostasis review context. supported_by: - reference_id: PMID:20616062 supporting_text: depletion of VPS4A, VPS4B, or any of the 11 different human ESCRT-III (CHMP) proteins inhibited abscission - reference_id: PMID:20616062 supporting_text: producing multipolar spindles (most ESCRT-III/VPS4 proteins) or monopolar spindles (CHMP2A or CHMP5) - reference_id: PMID:20616062 supporting_text: ESCRT-III/VPS4 proteins function at centrosomes to help regulate their maintenance or proliferation and then at midbodies during abscission - reference_id: file:human/CHMP5/CHMP5-notes.md supporting_text: Secondary ESCRT contexts should generally be kept as non-core. - term: id: GO:0005886 label: plasma membrane evidence_type: IDA original_reference_id: PMID:24878737 qualifier: located_in review: summary: Supported but non-core plasma membrane ESCRT context for CHMP5. action: KEEP_AS_NON_CORE reason: Plasma membrane localization in ESCRT/HIV or repair assays is a secondary pathway context and not the main CHMP5 proteostasis function. supported_by: - reference_id: PMID:15644320 supporting_text: CHMP5 depletion results in an increase in the release of infectious HIV-1 particles - reference_id: PMID:15644320 supporting_text: both LIP5 and CHMP5 function in MVB sorting, whereas only LIP5 is required for HIV release. - reference_id: file:human/CHMP5/CHMP5-notes.md supporting_text: 'Over-annotated: generic protein binding, cadherin binding, viral budding as a CHMP5 function, and LPS/MDP response terms inferred from induction or interaction context rather than a demonstrated CHMP5 response function.' - reference_id: PMID:24482116 supporting_text: ESCRT proteins were recruited within seconds to plasma membrane wounds - reference_id: PMID:24482116 supporting_text: repair of certain wounds is ensured by ESCRT-mediated extracellular shedding of wounded portions - reference_id: file:human/CHMP5/CHMP5-notes.md supporting_text: Secondary ESCRT contexts should generally be kept as non-core. - 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 CHMP5 autophagy/endolysosomal context: autophagy.' action: KEEP_AS_NON_CORE reason: Functional MVB/ESCRT activity supports autophagic clearance and infection-specific CHMP5 evidence exists, but the cached annotations do not show CHMP5-specific autophagosome sealing/maturation as the core function. supported_by: - reference_id: PMID:17984323 supporting_text: Functional multivesicular bodies are required for autophagic clearance - reference_id: PMID:17984323 supporting_text: functional MVBs are required to prevent accumulation of abnormal proteins - reference_id: PMID:30061757 supporting_text: CHMP5-one of the IcsB targets and a component of the ESCRT-III complex-specifically affected S. flexneri escape from host autophagy. - reference_id: file:human/CHMP5/CHMP5-notes.md supporting_text: the cached CHMP5 GOA autophagy annotations mostly derive from ESCRT-complex context rather than CHMP5-specific autophagosome sealing assays - term: id: GO:0006997 label: nucleus organization evidence_type: IMP original_reference_id: PMID:20616062 qualifier: involved_in review: summary: 'Plausible non-core ESCRT cell-cycle/centrosome context for CHMP5: nucleus organization.' action: KEEP_AS_NON_CORE reason: CHMP5 and other ESCRT-III/VPS4 proteins have reported cell-cycle and abscission phenotypes, but these are secondary to the MVB sorting and ESCRT recycling function in the proteostasis review context. supported_by: - reference_id: PMID:20616062 supporting_text: depletion of VPS4A, VPS4B, or any of the 11 different human ESCRT-III (CHMP) proteins inhibited abscission - reference_id: PMID:20616062 supporting_text: producing multipolar spindles (most ESCRT-III/VPS4 proteins) or monopolar spindles (CHMP2A or CHMP5) - reference_id: PMID:20616062 supporting_text: ESCRT-III/VPS4 proteins function at centrosomes to help regulate their maintenance or proliferation and then at midbodies during abscission - reference_id: file:human/CHMP5/CHMP5-notes.md supporting_text: Secondary ESCRT contexts should generally be kept as non-core. - term: id: GO:0007080 label: mitotic metaphase chromosome alignment evidence_type: IMP original_reference_id: PMID:20616062 qualifier: involved_in review: summary: 'Plausible non-core ESCRT cell-cycle/centrosome context for CHMP5: mitotic metaphase chromosome alignment.' action: KEEP_AS_NON_CORE reason: CHMP5 and other ESCRT-III/VPS4 proteins have reported cell-cycle and abscission phenotypes, but these are secondary to the MVB sorting and ESCRT recycling function in the proteostasis review context. supported_by: - reference_id: PMID:20616062 supporting_text: depletion of VPS4A, VPS4B, or any of the 11 different human ESCRT-III (CHMP) proteins inhibited abscission - reference_id: PMID:20616062 supporting_text: producing multipolar spindles (most ESCRT-III/VPS4 proteins) or monopolar spindles (CHMP2A or CHMP5) - reference_id: PMID:20616062 supporting_text: ESCRT-III/VPS4 proteins function at centrosomes to help regulate their maintenance or proliferation and then at midbodies during abscission - reference_id: file:human/CHMP5/CHMP5-notes.md supporting_text: Secondary ESCRT contexts should generally be kept as non-core. - term: id: GO:0030496 label: midbody evidence_type: IDA original_reference_id: PMID:26040712 qualifier: located_in review: summary: 'Plausible non-core ESCRT cell-cycle/centrosome context for CHMP5: midbody.' action: KEEP_AS_NON_CORE reason: CHMP5 and other ESCRT-III/VPS4 proteins have reported cell-cycle and abscission phenotypes, but these are secondary to the MVB sorting and ESCRT recycling function in the proteostasis review context. supported_by: - reference_id: PMID:20616062 supporting_text: depletion of VPS4A, VPS4B, or any of the 11 different human ESCRT-III (CHMP) proteins inhibited abscission - reference_id: PMID:20616062 supporting_text: producing multipolar spindles (most ESCRT-III/VPS4 proteins) or monopolar spindles (CHMP2A or CHMP5) - reference_id: PMID:20616062 supporting_text: ESCRT-III/VPS4 proteins function at centrosomes to help regulate their maintenance or proliferation and then at midbodies during abscission - reference_id: file:human/CHMP5/CHMP5-notes.md supporting_text: Secondary ESCRT contexts should generally be kept as non-core. - term: id: GO:0031468 label: nuclear membrane reassembly evidence_type: IMP original_reference_id: PMID:26040713 qualifier: involved_in review: summary: 'Plausible non-core ESCRT nuclear-envelope context for CHMP5: nuclear membrane reassembly.' action: KEEP_AS_NON_CORE reason: Nuclear envelope sealing/reassembly is a supported ESCRT-III pathway context, but CHMP5-specific evidence is centered on MVB sorting and LIP5/VPS4-mediated ESCRT recycling. supported_by: - reference_id: PMID:26040712 supporting_text: ESCRT-III, VPS4 and spastin cooperate to coordinate nuclear envelope sealing and spindle disassembly - reference_id: PMID:26040713 supporting_text: ESCRT-III controls nuclear envelope reformation - reference_id: file:human/CHMP5/CHMP5-notes.md supporting_text: Secondary ESCRT contexts should generally be kept as non-core. - term: id: GO:0032585 label: multivesicular body membrane evidence_type: IDA original_reference_id: PMID:16554368 qualifier: located_in review: summary: 'Supported CHMP5 endosomal/MVB membrane context: multivesicular body membrane.' action: ACCEPT reason: CHMP5 is a peripheral ESCRT-III component that cycles between cytosol and endosomal ESCRT assemblies, so the endosome/MVB membrane context is relevant to the core MVB sorting function. supported_by: - reference_id: UniProt:Q9NZZ3 supporting_text: involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs - reference_id: PMID:15644320 supporting_text: both LIP5 and CHMP5 function in MVB sorting - reference_id: PMID:15644320 supporting_text: Depletion of CHMP5 by siRNA does not affect the distribution or morphology of early endosomes, lysosomes, or Golgi but does result in reduced degradation of the EGFR - reference_id: file:human/CHMP5/CHMP5-notes.md supporting_text: 'Core: ESCRT-III complex membership, MVB sorting/assembly, ubiquitin-dependent cargo degradation through MVB sorting, ESCRT-III disassembly/recycling via LIP5/VTA1 and VPS4, and the endolysosomal degradation route that follows MVB sorting.' - reference_id: UniProt:Q9NZZ3 supporting_text: Probable peripherally associated component of the endosomal sorting required for transport complex III (ESCRT-III) - reference_id: PMID:16730941 supporting_text: known components of the human ESCRT III complex - reference_id: PMID:23105106 supporting_text: the ESCRT-III and VPS4 ATPase complexes catalyze the membrane fission events associated with these processes - reference_id: file:human/CHMP5/CHMP5-notes.md supporting_text: CHMP5 (UniProt Q9NZZ3) is a SNF7/ESCRT-III family protein best treated as an ESCRT-III regulatory component for endosomal MVB sorting and VPS4/LIP5-mediated ESCRT-III recycling. - term: id: GO:0036258 label: multivesicular body assembly evidence_type: NAS original_reference_id: PMID:16505166 qualifier: involved_in review: summary: 'Supported core CHMP5 MVB/endolysosomal sorting annotation: multivesicular body assembly.' action: ACCEPT reason: CHMP5 depletion impairs EGFR degradation and CHMP5-LIP5/VTA1-VPS4 biology places it in the ESCRT machinery required for MVB cargo sorting and downstream lysosomal degradation. supported_by: - reference_id: UniProt:Q9NZZ3 supporting_text: involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs - reference_id: PMID:15644320 supporting_text: both LIP5 and CHMP5 function in MVB sorting - reference_id: PMID:15644320 supporting_text: Depletion of CHMP5 by siRNA does not affect the distribution or morphology of early endosomes, lysosomes, or Golgi but does result in reduced degradation of the EGFR - reference_id: file:human/CHMP5/CHMP5-notes.md supporting_text: 'Core: ESCRT-III complex membership, MVB sorting/assembly, ubiquitin-dependent cargo degradation through MVB sorting, ESCRT-III disassembly/recycling via LIP5/VTA1 and VPS4, and the endolysosomal degradation route that follows MVB sorting.' - reference_id: UniProt:Q9NZZ3 supporting_text: enabling degradation of membrane proteins, such as stimulated growth factor receptors - reference_id: PMID:15644320 supporting_text: reduced degradation of the EGFR similar to silencing of LIP5 - reference_id: PMID:17984323 supporting_text: Functional multivesicular bodies are required for autophagic clearance - reference_id: file:human/CHMP5/CHMP5-notes.md supporting_text: 'Proteostasis-network context: CHMP5 supports endolysosomal degradation through ESCRT/MVB sorting' - term: id: GO:0039702 label: viral budding via host ESCRT complex evidence_type: IDA original_reference_id: PMID:24878737 qualifier: involved_in review: summary: 'Viral budding is not a core CHMP5 cellular function and is likely over-annotated here: viral budding via host ESCRT complex.' action: MARK_AS_OVER_ANNOTATED reason: The key CHMP5/LIP5 study found CHMP5 depletion increased infectious HIV-1 release and concluded that only LIP5 is required for HIV release, so viral-budding annotations should not be treated as CHMP5 core function. supported_by: - reference_id: PMID:15644320 supporting_text: CHMP5 depletion results in an increase in the release of infectious HIV-1 particles - reference_id: PMID:15644320 supporting_text: both LIP5 and CHMP5 function in MVB sorting, whereas only LIP5 is required for HIV release. - reference_id: file:human/CHMP5/CHMP5-notes.md supporting_text: 'Over-annotated: generic protein binding, cadherin binding, viral budding as a CHMP5 function, and LPS/MDP response terms inferred from induction or interaction context rather than a demonstrated CHMP5 response function.' - 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 CHMP5 MVB/endolysosomal sorting annotation: ubiquitin-dependent protein catabolic process via the multivesicular body sorting pathway.' action: ACCEPT reason: CHMP5 depletion impairs EGFR degradation and CHMP5-LIP5/VTA1-VPS4 biology places it in the ESCRT machinery required for MVB cargo sorting and downstream lysosomal degradation. supported_by: - reference_id: UniProt:Q9NZZ3 supporting_text: involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs - reference_id: PMID:15644320 supporting_text: both LIP5 and CHMP5 function in MVB sorting - reference_id: PMID:15644320 supporting_text: Depletion of CHMP5 by siRNA does not affect the distribution or morphology of early endosomes, lysosomes, or Golgi but does result in reduced degradation of the EGFR - reference_id: file:human/CHMP5/CHMP5-notes.md supporting_text: 'Core: ESCRT-III complex membership, MVB sorting/assembly, ubiquitin-dependent cargo degradation through MVB sorting, ESCRT-III disassembly/recycling via LIP5/VTA1 and VPS4, and the endolysosomal degradation route that follows MVB sorting.' - reference_id: UniProt:Q9NZZ3 supporting_text: enabling degradation of membrane proteins, such as stimulated growth factor receptors - reference_id: PMID:15644320 supporting_text: reduced degradation of the EGFR similar to silencing of LIP5 - reference_id: PMID:17984323 supporting_text: Functional multivesicular bodies are required for autophagic clearance - reference_id: file:human/CHMP5/CHMP5-notes.md supporting_text: 'Proteostasis-network context: CHMP5 supports endolysosomal degradation through ESCRT/MVB sorting' - term: id: GO:0046761 label: viral budding from plasma membrane evidence_type: IDA original_reference_id: PMID:24878737 qualifier: involved_in review: summary: 'Viral budding is not a core CHMP5 cellular function and is likely over-annotated here: viral budding from plasma membrane.' action: MARK_AS_OVER_ANNOTATED reason: The key CHMP5/LIP5 study found CHMP5 depletion increased infectious HIV-1 release and concluded that only LIP5 is required for HIV release, so viral-budding annotations should not be treated as CHMP5 core function. supported_by: - reference_id: PMID:15644320 supporting_text: CHMP5 depletion results in an increase in the release of infectious HIV-1 particles - reference_id: PMID:15644320 supporting_text: both LIP5 and CHMP5 function in MVB sorting, whereas only LIP5 is required for HIV release. - reference_id: file:human/CHMP5/CHMP5-notes.md supporting_text: 'Over-annotated: generic protein binding, cadherin binding, viral budding as a CHMP5 function, and LPS/MDP response terms inferred from induction or interaction context rather than a demonstrated CHMP5 response function.' - term: id: GO:0051469 label: vesicle fusion with vacuole evidence_type: NAS original_reference_id: PMID:16505166 qualifier: involved_in review: summary: vesicle fusion with vacuole is an over-specific/organellar endpoint for CHMP5 and should be generalized to late endosome-to-lysosome transport. action: MODIFY reason: The evidence supports ESCRT/MVB cargo sorting and downstream degradative trafficking. It does not establish CHMP5 as a direct vesicle-fusion factor. supported_by: - reference_id: UniProt:Q9NZZ3 supporting_text: enabling degradation of membrane proteins, such as stimulated growth factor receptors - reference_id: PMID:15644320 supporting_text: reduced degradation of the EGFR similar to silencing of LIP5 - reference_id: PMID:17984323 supporting_text: Functional multivesicular bodies are required for autophagic clearance - reference_id: file:human/CHMP5/CHMP5-notes.md supporting_text: 'Proteostasis-network context: CHMP5 supports endolysosomal degradation through ESCRT/MVB sorting' 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: multivesicular body-lysosome fusion is an over-specific/organellar endpoint for CHMP5 and should be generalized to late endosome-to-lysosome transport. action: MODIFY reason: The evidence supports ESCRT/MVB cargo sorting and downstream degradative trafficking. It does not establish CHMP5 as a direct vesicle-fusion factor. supported_by: - reference_id: UniProt:Q9NZZ3 supporting_text: enabling degradation of membrane proteins, such as stimulated growth factor receptors - reference_id: PMID:15644320 supporting_text: reduced degradation of the EGFR similar to silencing of LIP5 - reference_id: PMID:17984323 supporting_text: Functional multivesicular bodies are required for autophagic clearance - reference_id: file:human/CHMP5/CHMP5-notes.md supporting_text: 'Proteostasis-network context: CHMP5 supports endolysosomal degradation through ESCRT/MVB sorting' 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 non-core ESCRT cell-cycle/centrosome context for CHMP5: midbody abscission.' action: KEEP_AS_NON_CORE reason: CHMP5 and other ESCRT-III/VPS4 proteins have reported cell-cycle and abscission phenotypes, but these are secondary to the MVB sorting and ESCRT recycling function in the proteostasis review context. supported_by: - reference_id: PMID:20616062 supporting_text: depletion of VPS4A, VPS4B, or any of the 11 different human ESCRT-III (CHMP) proteins inhibited abscission - reference_id: PMID:20616062 supporting_text: producing multipolar spindles (most ESCRT-III/VPS4 proteins) or monopolar spindles (CHMP2A or CHMP5) - reference_id: PMID:20616062 supporting_text: ESCRT-III/VPS4 proteins function at centrosomes to help regulate their maintenance or proliferation and then at midbodies during abscission - reference_id: file:human/CHMP5/CHMP5-notes.md supporting_text: Secondary ESCRT contexts should generally be kept as non-core. - term: id: GO:0071985 label: multivesicular body sorting pathway evidence_type: IDA original_reference_id: PMID:16554368 qualifier: involved_in review: summary: 'Supported core CHMP5 MVB/endolysosomal sorting annotation: multivesicular body sorting pathway.' action: ACCEPT reason: CHMP5 depletion impairs EGFR degradation and CHMP5-LIP5/VTA1-VPS4 biology places it in the ESCRT machinery required for MVB cargo sorting and downstream lysosomal degradation. supported_by: - reference_id: UniProt:Q9NZZ3 supporting_text: involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs - reference_id: PMID:15644320 supporting_text: both LIP5 and CHMP5 function in MVB sorting - reference_id: PMID:15644320 supporting_text: Depletion of CHMP5 by siRNA does not affect the distribution or morphology of early endosomes, lysosomes, or Golgi but does result in reduced degradation of the EGFR - reference_id: file:human/CHMP5/CHMP5-notes.md supporting_text: 'Core: ESCRT-III complex membership, MVB sorting/assembly, ubiquitin-dependent cargo degradation through MVB sorting, ESCRT-III disassembly/recycling via LIP5/VTA1 and VPS4, and the endolysosomal degradation route that follows MVB sorting.' - reference_id: UniProt:Q9NZZ3 supporting_text: enabling degradation of membrane proteins, such as stimulated growth factor receptors - reference_id: PMID:15644320 supporting_text: reduced degradation of the EGFR similar to silencing of LIP5 - reference_id: PMID:17984323 supporting_text: Functional multivesicular bodies are required for autophagic clearance - reference_id: file:human/CHMP5/CHMP5-notes.md supporting_text: 'Proteostasis-network context: CHMP5 supports endolysosomal degradation through ESCRT/MVB sorting' - term: id: GO:0090148 label: membrane fission evidence_type: NAS original_reference_id: PMID:19234443 qualifier: involved_in review: summary: Supported ESCRT-pathway membrane-fission output for CHMP5. action: ACCEPT reason: Membrane fission is a core ESCRT-III pathway output. CHMP5 is best viewed as a regulatory ESCRT-III/LIP5-VPS4 component rather than the principal Snf7-like scission polymer, but the annotation is acceptable as pathway-level function. supported_by: - reference_id: UniProt:Q9NZZ3 supporting_text: Probable peripherally associated component of the endosomal sorting required for transport complex III (ESCRT-III) - reference_id: PMID:16730941 supporting_text: known components of the human ESCRT III complex - reference_id: PMID:23105106 supporting_text: the ESCRT-III and VPS4 ATPase complexes catalyze the membrane fission events associated with these processes - reference_id: file:human/CHMP5/CHMP5-notes.md supporting_text: CHMP5 (UniProt Q9NZZ3) is a SNF7/ESCRT-III family protein best treated as an ESCRT-III regulatory component for endosomal MVB sorting and VPS4/LIP5-mediated ESCRT-III recycling. - reference_id: PMID:18385515 supporting_text: LIP5 binds preferentially to soluble CHMP5 - reference_id: PMID:18385515 supporting_text: These studies point to a role for direct binding between LIP5 and ESCRT-III proteins - reference_id: PMID:23105106 supporting_text: promoting assembly of active VPS4 enzymes on the polymeric ESCRT-III substrate - reference_id: PMID:23105106 supporting_text: formation of stable VPS4 complexes with both LIP5 and CHMP5 requires LIP5 to bind both a MIM1-containing ESCRT-III protein and CHMP5 - reference_id: file:human/CHMP5/CHMP5-notes.md supporting_text: The mechanistic refinement is that CHMP5 binds LIP5/VTA1 and helps regulate VPS4 activation/disassembly of ESCRT-III rather than acting as a CHMP4/Snf7-like primary filament/scission subunit. - 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 CHMP5 autophagy/endolysosomal context: autophagosome maturation.' action: KEEP_AS_NON_CORE reason: Functional MVB/ESCRT activity supports autophagic clearance and infection-specific CHMP5 evidence exists, but the cached annotations do not show CHMP5-specific autophagosome sealing/maturation as the core function. supported_by: - reference_id: PMID:17984323 supporting_text: Functional multivesicular bodies are required for autophagic clearance - reference_id: PMID:17984323 supporting_text: functional MVBs are required to prevent accumulation of abnormal proteins - reference_id: PMID:30061757 supporting_text: CHMP5-one of the IcsB targets and a component of the ESCRT-III complex-specifically affected S. flexneri escape from host autophagy. - reference_id: file:human/CHMP5/CHMP5-notes.md supporting_text: the cached CHMP5 GOA autophagy annotations mostly derive from ESCRT-complex context rather than CHMP5-specific autophagosome sealing assays - term: id: GO:1901673 label: regulation of mitotic spindle assembly evidence_type: IMP original_reference_id: PMID:20616062 qualifier: involved_in review: summary: 'Plausible non-core ESCRT cell-cycle/centrosome context for CHMP5: regulation of mitotic spindle assembly.' action: KEEP_AS_NON_CORE reason: CHMP5 and other ESCRT-III/VPS4 proteins have reported cell-cycle and abscission phenotypes, but these are secondary to the MVB sorting and ESCRT recycling function in the proteostasis review context. supported_by: - reference_id: PMID:20616062 supporting_text: depletion of VPS4A, VPS4B, or any of the 11 different human ESCRT-III (CHMP) proteins inhibited abscission - reference_id: PMID:20616062 supporting_text: producing multipolar spindles (most ESCRT-III/VPS4 proteins) or monopolar spindles (CHMP2A or CHMP5) - reference_id: PMID:20616062 supporting_text: ESCRT-III/VPS4 proteins function at centrosomes to help regulate their maintenance or proliferation and then at midbodies during abscission - reference_id: file:human/CHMP5/CHMP5-notes.md supporting_text: Secondary ESCRT contexts should generally be kept as non-core. - term: id: GO:1902774 label: late endosome to lysosome transport evidence_type: IMP original_reference_id: PMID:17984323 qualifier: involved_in review: summary: Supported CHMP5 endolysosomal degradation route annotation. action: ACCEPT reason: CHMP5-mediated MVB sorting supports delivery of cargo such as EGFR into the degradative endolysosomal route; this term is an appropriate pathway endpoint for the MVB sorting function. supported_by: - reference_id: UniProt:Q9NZZ3 supporting_text: involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs - reference_id: PMID:15644320 supporting_text: both LIP5 and CHMP5 function in MVB sorting - reference_id: PMID:15644320 supporting_text: Depletion of CHMP5 by siRNA does not affect the distribution or morphology of early endosomes, lysosomes, or Golgi but does result in reduced degradation of the EGFR - reference_id: file:human/CHMP5/CHMP5-notes.md supporting_text: 'Core: ESCRT-III complex membership, MVB sorting/assembly, ubiquitin-dependent cargo degradation through MVB sorting, ESCRT-III disassembly/recycling via LIP5/VTA1 and VPS4, and the endolysosomal degradation route that follows MVB sorting.' - reference_id: UniProt:Q9NZZ3 supporting_text: enabling degradation of membrane proteins, such as stimulated growth factor receptors - reference_id: PMID:15644320 supporting_text: reduced degradation of the EGFR similar to silencing of LIP5 - reference_id: PMID:17984323 supporting_text: Functional multivesicular bodies are required for autophagic clearance - reference_id: file:human/CHMP5/CHMP5-notes.md supporting_text: 'Proteostasis-network context: CHMP5 supports endolysosomal degradation through ESCRT/MVB sorting' - 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 CHMP5 autophagy/endolysosomal context: amphisome membrane.' action: KEEP_AS_NON_CORE reason: Functional MVB/ESCRT activity supports autophagic clearance and infection-specific CHMP5 evidence exists, but the cached annotations do not show CHMP5-specific autophagosome sealing/maturation as the core function. supported_by: - reference_id: PMID:17984323 supporting_text: Functional multivesicular bodies are required for autophagic clearance - reference_id: PMID:17984323 supporting_text: functional MVBs are required to prevent accumulation of abnormal proteins - reference_id: PMID:30061757 supporting_text: CHMP5-one of the IcsB targets and a component of the ESCRT-III complex-specifically affected S. flexneri escape from host autophagy. - reference_id: file:human/CHMP5/CHMP5-notes.md supporting_text: the cached CHMP5 GOA autophagy annotations mostly derive from ESCRT-complex context rather than CHMP5-specific autophagosome sealing assays - term: id: GO:0030496 label: midbody evidence_type: EXP original_reference_id: PMID:17853893 qualifier: located_in review: summary: 'Plausible non-core ESCRT cell-cycle/centrosome context for CHMP5: midbody.' action: KEEP_AS_NON_CORE reason: CHMP5 and other ESCRT-III/VPS4 proteins have reported cell-cycle and abscission phenotypes, but these are secondary to the MVB sorting and ESCRT recycling function in the proteostasis review context. supported_by: - reference_id: PMID:20616062 supporting_text: depletion of VPS4A, VPS4B, or any of the 11 different human ESCRT-III (CHMP) proteins inhibited abscission - reference_id: PMID:20616062 supporting_text: producing multipolar spindles (most ESCRT-III/VPS4 proteins) or monopolar spindles (CHMP2A or CHMP5) - reference_id: PMID:20616062 supporting_text: ESCRT-III/VPS4 proteins function at centrosomes to help regulate their maintenance or proliferation and then at midbodies during abscission - reference_id: file:human/CHMP5/CHMP5-notes.md supporting_text: Secondary ESCRT contexts should generally be kept as non-core. - term: id: GO:0071222 label: cellular response to lipopolysaccharide evidence_type: IMP original_reference_id: PMID:27812135 qualifier: involved_in review: summary: cellular response to lipopolysaccharide is not established as a CHMP5 core response function. action: MARK_AS_OVER_ANNOTATED reason: PMID:27812135 supports CHMP5 as a NOD2-interacting protein and reports LPS/MDP induction context, but this is better treated as interaction/regulatory context than an involved_in response annotation for CHMP5. supported_by: - reference_id: PMID:27812135 supporting_text: CHMP5ESCRTIII proteins are required for late MVB formation and their fusion with the lysosome - reference_id: file:human/CHMP5/CHMP5-notes.md supporting_text: The NOD2/LPS/MDP annotations are not core CHMP5 function. - reference_id: file:human/CHMP5/CHMP5-notes.md supporting_text: the study itself says these new interacting proteins did not appear to be major NOD2-dependent NF-kappaB regulators in the assay - term: id: GO:0071225 label: cellular response to muramyl dipeptide evidence_type: IMP original_reference_id: PMID:27812135 qualifier: involved_in review: summary: cellular response to muramyl dipeptide is not established as a CHMP5 core response function. action: MARK_AS_OVER_ANNOTATED reason: PMID:27812135 supports CHMP5 as a NOD2-interacting protein and reports LPS/MDP induction context, but this is better treated as interaction/regulatory context than an involved_in response annotation for CHMP5. supported_by: - reference_id: PMID:27812135 supporting_text: CHMP5ESCRTIII proteins are required for late MVB formation and their fusion with the lysosome - reference_id: file:human/CHMP5/CHMP5-notes.md supporting_text: The NOD2/LPS/MDP annotations are not core CHMP5 function. - reference_id: file:human/CHMP5/CHMP5-notes.md supporting_text: the study itself says these new interacting proteins did not appear to be major NOD2-dependent NF-kappaB regulators in the assay - term: id: GO:0045296 label: cadherin binding evidence_type: HDA original_reference_id: PMID:25468996 qualifier: enables review: summary: Cadherin binding from high-throughput proteomics is not informative for CHMP5 function. action: MARK_AS_OVER_ANNOTATED reason: The cadherin-binding annotation is from broad affinity proteomics and does not connect to the supported ESCRT/MVB/LIP5-VPS4 role of CHMP5. supported_by: - reference_id: PMID:25468996 supporting_text: E-cadherin interactome complexity and robustness resolved by quantitative proteomics - reference_id: file:human/CHMP5/CHMP5-notes.md supporting_text: 'Over-annotated: generic protein binding, cadherin binding, viral budding as a CHMP5 function, and LPS/MDP response terms inferred from induction or interaction context rather than a demonstrated CHMP5 response function.' - term: id: GO:0036258 label: multivesicular body assembly evidence_type: NAS original_reference_id: PMID:20588296 qualifier: involved_in review: summary: 'Supported core CHMP5 MVB/endolysosomal sorting annotation: multivesicular body assembly.' action: ACCEPT reason: CHMP5 depletion impairs EGFR degradation and CHMP5-LIP5/VTA1-VPS4 biology places it in the ESCRT machinery required for MVB cargo sorting and downstream lysosomal degradation. supported_by: - reference_id: UniProt:Q9NZZ3 supporting_text: involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs - reference_id: PMID:15644320 supporting_text: both LIP5 and CHMP5 function in MVB sorting - reference_id: PMID:15644320 supporting_text: Depletion of CHMP5 by siRNA does not affect the distribution or morphology of early endosomes, lysosomes, or Golgi but does result in reduced degradation of the EGFR - reference_id: file:human/CHMP5/CHMP5-notes.md supporting_text: 'Core: ESCRT-III complex membership, MVB sorting/assembly, ubiquitin-dependent cargo degradation through MVB sorting, ESCRT-III disassembly/recycling via LIP5/VTA1 and VPS4, and the endolysosomal degradation route that follows MVB sorting.' - reference_id: UniProt:Q9NZZ3 supporting_text: enabling degradation of membrane proteins, such as stimulated growth factor receptors - reference_id: PMID:15644320 supporting_text: reduced degradation of the EGFR similar to silencing of LIP5 - reference_id: PMID:17984323 supporting_text: Functional multivesicular bodies are required for autophagic clearance - reference_id: file:human/CHMP5/CHMP5-notes.md supporting_text: 'Proteostasis-network context: CHMP5 supports endolysosomal degradation through ESCRT/MVB sorting' - term: id: GO:1904903 label: ESCRT III complex disassembly evidence_type: NAS original_reference_id: PMID:20588296 qualifier: involved_in review: summary: Supported core CHMP5 role in ESCRT-III complex disassembly/recycling. action: ACCEPT reason: The strongest CHMP5-specific mechanism is binding LIP5/VTA1 and contributing to VPS4 engagement/activation on ESCRT-III assemblies, making ESCRT-III disassembly a core mechanistic process. supported_by: - reference_id: PMID:18385515 supporting_text: LIP5 binds preferentially to soluble CHMP5 - reference_id: PMID:18385515 supporting_text: These studies point to a role for direct binding between LIP5 and ESCRT-III proteins - reference_id: PMID:23105106 supporting_text: promoting assembly of active VPS4 enzymes on the polymeric ESCRT-III substrate - reference_id: PMID:23105106 supporting_text: formation of stable VPS4 complexes with both LIP5 and CHMP5 requires LIP5 to bind both a MIM1-containing ESCRT-III protein and CHMP5 - reference_id: file:human/CHMP5/CHMP5-notes.md supporting_text: The mechanistic refinement is that CHMP5 binds LIP5/VTA1 and helps regulate VPS4 activation/disassembly of ESCRT-III rather than acting as a CHMP4/Snf7-like primary filament/scission subunit. - reference_id: UniProt:Q9NZZ3 supporting_text: Probable peripherally associated component of the endosomal sorting required for transport complex III (ESCRT-III) - reference_id: PMID:16730941 supporting_text: known components of the human ESCRT III complex - reference_id: PMID:23105106 supporting_text: the ESCRT-III and VPS4 ATPase complexes catalyze the membrane fission events associated with these processes - reference_id: file:human/CHMP5/CHMP5-notes.md supporting_text: CHMP5 (UniProt Q9NZZ3) is a SNF7/ESCRT-III family protein best treated as an ESCRT-III regulatory component for endosomal MVB sorting and VPS4/LIP5-mediated ESCRT-III recycling. - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:18385515 qualifier: enables review: summary: Generic protein binding does not capture the specific CHMP5/LIP5/VPS4-ESCRT regulatory mechanism. action: MARK_AS_OVER_ANNOTATED reason: The interactions with LIP5/VTA1 and other ESCRT-associated proteins are biologically meaningful, but the GO term protein binding is too generic to capture CHMP5 function. supported_by: - reference_id: PMID:15644320 supporting_text: We identify CHMP5 as a LIP5-binding protein and show that CHMP5 is primarily cytosolic. - reference_id: PMID:18385515 supporting_text: LIP5 binds preferentially to soluble CHMP5 - reference_id: PMID:23105106 supporting_text: the second LIP5 MIT module binds with unusually high affinity to a novel MIM element within the ESCRT-III protein CHMP5 - reference_id: file:human/CHMP5/CHMP5-notes.md supporting_text: 'Over-annotated: generic protein binding, cadherin binding, viral budding as a CHMP5 function, and LPS/MDP response terms inferred from induction or interaction context rather than a demonstrated CHMP5 response function.' - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:23105106 qualifier: enables review: summary: Generic protein binding does not capture the specific CHMP5/LIP5/VPS4-ESCRT regulatory mechanism. action: MARK_AS_OVER_ANNOTATED reason: The interactions with LIP5/VTA1 and other ESCRT-associated proteins are biologically meaningful, but the GO term protein binding is too generic to capture CHMP5 function. supported_by: - reference_id: PMID:15644320 supporting_text: We identify CHMP5 as a LIP5-binding protein and show that CHMP5 is primarily cytosolic. - reference_id: PMID:18385515 supporting_text: LIP5 binds preferentially to soluble CHMP5 - reference_id: PMID:23105106 supporting_text: the second LIP5 MIT module binds with unusually high affinity to a novel MIM element within the ESCRT-III protein CHMP5 - reference_id: file:human/CHMP5/CHMP5-notes.md supporting_text: 'Over-annotated: generic protein binding, cadherin binding, viral budding as a CHMP5 function, and LPS/MDP response terms inferred from induction or interaction context rather than a demonstrated CHMP5 response function.' - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:15644320 qualifier: enables review: summary: Generic protein binding does not capture the specific CHMP5/LIP5/VPS4-ESCRT regulatory mechanism. action: MARK_AS_OVER_ANNOTATED reason: The interactions with LIP5/VTA1 and other ESCRT-associated proteins are biologically meaningful, but the GO term protein binding is too generic to capture CHMP5 function. supported_by: - reference_id: PMID:15644320 supporting_text: We identify CHMP5 as a LIP5-binding protein and show that CHMP5 is primarily cytosolic. - reference_id: PMID:18385515 supporting_text: LIP5 binds preferentially to soluble CHMP5 - reference_id: PMID:23105106 supporting_text: the second LIP5 MIT module binds with unusually high affinity to a novel MIM element within the ESCRT-III protein CHMP5 - reference_id: file:human/CHMP5/CHMP5-notes.md supporting_text: 'Over-annotated: generic protein binding, cadherin binding, viral budding as a CHMP5 function, and LPS/MDP response terms inferred from induction or interaction context rather than a demonstrated CHMP5 response function.' - term: id: GO:0005829 label: cytosol evidence_type: IDA original_reference_id: PMID:15644320 qualifier: located_in review: summary: 'True or plausible broad CHMP5 location: cytosol.' action: KEEP_AS_NON_CORE reason: CHMP5 is primarily cytosolic and can be detected in broad compartments, but broad locations do not define the core function. supported_by: - reference_id: UniProt:Q9NZZ3 supporting_text: Cytoplasm, cytosol - reference_id: PMID:15644320 supporting_text: We identify CHMP5 as a LIP5-binding protein and show that CHMP5 is primarily cytosolic. - reference_id: file:human/CHMP5/CHMP5-notes.md supporting_text: 'Non-core: cytosol/nucleus/exosome locations, midbody/cytokinesis, spindle/centrosome, nuclear envelope/pore reassembly, plasma membrane repair, infection/autophagy contexts, and viral budding.' - term: id: GO:0046755 label: viral budding evidence_type: IMP original_reference_id: PMID:15644320 qualifier: involved_in review: summary: 'Viral budding is not a core CHMP5 cellular function and is likely over-annotated here: viral budding.' action: MARK_AS_OVER_ANNOTATED reason: The key CHMP5/LIP5 study found CHMP5 depletion increased infectious HIV-1 release and concluded that only LIP5 is required for HIV release, so viral-budding annotations should not be treated as CHMP5 core function. supported_by: - reference_id: PMID:15644320 supporting_text: CHMP5 depletion results in an increase in the release of infectious HIV-1 particles - reference_id: PMID:15644320 supporting_text: both LIP5 and CHMP5 function in MVB sorting, whereas only LIP5 is required for HIV release. - reference_id: file:human/CHMP5/CHMP5-notes.md supporting_text: 'Over-annotated: generic protein binding, cadherin binding, viral budding as a CHMP5 function, and LPS/MDP response terms inferred from induction or interaction context rather than a demonstrated CHMP5 response function.' - term: id: GO:0071985 label: multivesicular body sorting pathway evidence_type: IMP original_reference_id: PMID:15644320 qualifier: involved_in review: summary: 'Supported core CHMP5 MVB/endolysosomal sorting annotation: multivesicular body sorting pathway.' action: ACCEPT reason: CHMP5 depletion impairs EGFR degradation and CHMP5-LIP5/VTA1-VPS4 biology places it in the ESCRT machinery required for MVB cargo sorting and downstream lysosomal degradation. supported_by: - reference_id: UniProt:Q9NZZ3 supporting_text: involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs - reference_id: PMID:15644320 supporting_text: both LIP5 and CHMP5 function in MVB sorting - reference_id: PMID:15644320 supporting_text: Depletion of CHMP5 by siRNA does not affect the distribution or morphology of early endosomes, lysosomes, or Golgi but does result in reduced degradation of the EGFR - reference_id: file:human/CHMP5/CHMP5-notes.md supporting_text: 'Core: ESCRT-III complex membership, MVB sorting/assembly, ubiquitin-dependent cargo degradation through MVB sorting, ESCRT-III disassembly/recycling via LIP5/VTA1 and VPS4, and the endolysosomal degradation route that follows MVB sorting.' - reference_id: UniProt:Q9NZZ3 supporting_text: enabling degradation of membrane proteins, such as stimulated growth factor receptors - reference_id: PMID:15644320 supporting_text: reduced degradation of the EGFR similar to silencing of LIP5 - reference_id: PMID:17984323 supporting_text: Functional multivesicular bodies are required for autophagic clearance - reference_id: file:human/CHMP5/CHMP5-notes.md supporting_text: 'Proteostasis-network context: CHMP5 supports endolysosomal degradation through ESCRT/MVB sorting' - term: id: GO:0010824 label: regulation of centrosome duplication evidence_type: IMP original_reference_id: PMID:20616062 qualifier: involved_in review: summary: 'Plausible non-core ESCRT cell-cycle/centrosome context for CHMP5: regulation of centrosome duplication.' action: KEEP_AS_NON_CORE reason: CHMP5 and other ESCRT-III/VPS4 proteins have reported cell-cycle and abscission phenotypes, but these are secondary to the MVB sorting and ESCRT recycling function in the proteostasis review context. supported_by: - reference_id: PMID:20616062 supporting_text: depletion of VPS4A, VPS4B, or any of the 11 different human ESCRT-III (CHMP) proteins inhibited abscission - reference_id: PMID:20616062 supporting_text: producing multipolar spindles (most ESCRT-III/VPS4 proteins) or monopolar spindles (CHMP2A or CHMP5) - reference_id: PMID:20616062 supporting_text: ESCRT-III/VPS4 proteins function at centrosomes to help regulate their maintenance or proliferation and then at midbodies during abscission - reference_id: file:human/CHMP5/CHMP5-notes.md supporting_text: Secondary ESCRT contexts should generally be kept as non-core. - term: id: GO:0070062 label: extracellular exosome evidence_type: HDA original_reference_id: PMID:23533145 qualifier: located_in review: summary: Extracellular exosome detection is retained as broad non-core location context. action: KEEP_AS_NON_CORE reason: High-throughput exosome proteomics can be compatible with ESCRT/exosome biology, but it does not establish the CHMP5 core cellular function. supported_by: - reference_id: PMID:23533145 supporting_text: In-depth proteomic analyses of exosomes isolated from expressed prostatic secretions in urine - 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 and potential functional implications for exosome biogenesis - reference_id: file:human/CHMP5/CHMP5-notes.md supporting_text: 'Non-core: cytosol/nucleus/exosome locations, midbody/cytokinesis, spindle/centrosome, nuclear envelope/pore reassembly, plasma membrane repair, infection/autophagy contexts, and viral budding.' - term: id: GO:0070062 label: extracellular exosome evidence_type: HDA original_reference_id: PMID:19056867 qualifier: located_in review: summary: Extracellular exosome detection is retained as broad non-core location context. action: KEEP_AS_NON_CORE reason: High-throughput exosome proteomics can be compatible with ESCRT/exosome biology, but it does not establish the CHMP5 core cellular function. supported_by: - reference_id: PMID:23533145 supporting_text: In-depth proteomic analyses of exosomes isolated from expressed prostatic secretions in urine - 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 and potential functional implications for exosome biogenesis - reference_id: file:human/CHMP5/CHMP5-notes.md supporting_text: 'Non-core: cytosol/nucleus/exosome locations, midbody/cytokinesis, spindle/centrosome, nuclear envelope/pore reassembly, plasma membrane repair, infection/autophagy contexts, and viral budding.' - term: id: GO:0070062 label: extracellular exosome evidence_type: HDA original_reference_id: PMID:20458337 qualifier: located_in review: summary: Extracellular exosome detection is retained as broad non-core location context. action: KEEP_AS_NON_CORE reason: High-throughput exosome proteomics can be compatible with ESCRT/exosome biology, but it does not establish the CHMP5 core cellular function. supported_by: - reference_id: PMID:23533145 supporting_text: In-depth proteomic analyses of exosomes isolated from expressed prostatic secretions in urine - 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 and potential functional implications for exosome biogenesis - reference_id: file:human/CHMP5/CHMP5-notes.md supporting_text: 'Non-core: cytosol/nucleus/exosome locations, midbody/cytokinesis, spindle/centrosome, nuclear envelope/pore reassembly, plasma membrane repair, infection/autophagy contexts, and viral budding.' - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:21543490 qualifier: enables review: summary: Generic protein binding does not capture the specific CHMP5/LIP5/VPS4-ESCRT regulatory mechanism. action: MARK_AS_OVER_ANNOTATED reason: The interactions with LIP5/VTA1 and other ESCRT-associated proteins are biologically meaningful, but the GO term protein binding is too generic to capture CHMP5 function. supported_by: - reference_id: PMID:15644320 supporting_text: We identify CHMP5 as a LIP5-binding protein and show that CHMP5 is primarily cytosolic. - reference_id: PMID:18385515 supporting_text: LIP5 binds preferentially to soluble CHMP5 - reference_id: PMID:23105106 supporting_text: the second LIP5 MIT module binds with unusually high affinity to a novel MIM element within the ESCRT-III protein CHMP5 - reference_id: file:human/CHMP5/CHMP5-notes.md supporting_text: 'Over-annotated: generic protein binding, cadherin binding, viral budding as a CHMP5 function, and LPS/MDP response terms inferred from induction or interaction context rather than a demonstrated CHMP5 response function.' - 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 CHMP5 location: cytosol.' action: KEEP_AS_NON_CORE reason: CHMP5 is primarily cytosolic and can be detected in broad compartments, but broad locations do not define the core function. supported_by: - reference_id: UniProt:Q9NZZ3 supporting_text: Cytoplasm, cytosol - reference_id: PMID:15644320 supporting_text: We identify CHMP5 as a LIP5-binding protein and show that CHMP5 is primarily cytosolic. - reference_id: file:human/CHMP5/CHMP5-notes.md supporting_text: 'Non-core: cytosol/nucleus/exosome locations, midbody/cytokinesis, spindle/centrosome, nuclear envelope/pore reassembly, plasma membrane repair, infection/autophagy contexts, and viral budding.' - 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 CHMP5 location: cytosol.' action: KEEP_AS_NON_CORE reason: CHMP5 is primarily cytosolic and can be detected in broad compartments, but broad locations do not define the core function. supported_by: - reference_id: UniProt:Q9NZZ3 supporting_text: Cytoplasm, cytosol - reference_id: PMID:15644320 supporting_text: We identify CHMP5 as a LIP5-binding protein and show that CHMP5 is primarily cytosolic. - reference_id: file:human/CHMP5/CHMP5-notes.md supporting_text: 'Non-core: cytosol/nucleus/exosome locations, midbody/cytokinesis, spindle/centrosome, nuclear envelope/pore reassembly, plasma membrane repair, infection/autophagy contexts, and viral budding.' 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:0000052 title: Gene Ontology annotation based on curation of immunofluorescence data findings: [] - id: GO_REF:0000107 title: Automatic transfer of experimentally verified manual GO annotation data to orthologs using Ensembl Compara findings: [] - id: GO_REF:0000117 title: Electronic Gene Ontology annotations created by ARBA machine learning models findings: [] - id: GO_REF:0000120 title: Combined Automated Annotation using Multiple IEA Methods findings: [] - id: PMID:15644320 title: The role of LIP5 and CHMP5 in multivesicular body formation and HIV-1 budding in mammalian cells. 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:17711858 title: The MIT domain of UBPY constitutes a CHMP binding and endosomal localization signal required for efficient epidermal growth factor receptor degradation. findings: [] - id: PMID:17853893 title: Human ESCRT and ALIX proteins interact with proteins of the midbody and function in cytokinesis. findings: [] - id: PMID:17984323 title: Functional multivesicular bodies are required for autophagic clearance of protein aggregates associated with neurodegenerative disease. findings: [] - id: PMID:18385515 title: Novel interactions of ESCRT-III with LIP5 and VPS4 and their implications for ESCRT-III disassembly. 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: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:21988832 title: Toward an understanding of the protein interaction network of the human liver. findings: [] - id: PMID:23105106 title: Interactions of the human LIP5 regulatory protein with endosomal sorting complexes required for transport. findings: [] - id: PMID:23533145 title: In-depth proteomic analyses of exosomes isolated from expressed prostatic secretions in urine. 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:25416956 title: A proteome-scale map of the human interactome network. findings: [] - id: PMID:25468996 title: E-cadherin interactome complexity and robustness resolved by quantitative proteomics. 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:26496610 title: A human interactome in three quantitative dimensions organized by stoichiometries and abundances. findings: [] - id: PMID:27812135 title: Characterization and Genetic Analyses of New Genes Coding for NOD2 Interacting Proteins. findings: [] - id: PMID:28514442 title: Architecture of the human interactome defines protein communities and disease networks. findings: [] - id: PMID:32296183 title: A reference map of the human binary protein interactome. 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: UniProt:Q9NZZ3 title: UniProtKB entry for human CHMP5 findings: - statement: UniProt describes CHMP5 as an ESCRT-III-associated component involved in MVB formation/sorting and cytosolic/endosome membrane localization. - id: PMID:30061757 title: "N(\u03B5)-fatty acylation of multiple membrane-associated proteins by Shigella IcsB effector to modulate host function." findings: - statement: Shigella IcsB modifies CHMP5 and CHMP5 knockout affects S. flexneri escape from host autophagy. - id: file:human/CHMP5/CHMP5-notes.md title: Local curation notes for CHMP5 findings: - statement: Local synthesis identifies CHMP5-LIP5/VTA1-VPS4 regulation of ESCRT-III recycling plus MVB sorting as core, with viral, nuclear-envelope, cytokinesis, repair, NOD2, and infection/autophagy contexts treated as secondary or over-annotated where appropriate. core_functions: - description: CHMP5 is an ESCRT-III-associated regulatory component for endosomal multivesicular body sorting and ESCRT-III recycling. Through a high-affinity CHMP5-LIP5/VTA1 interaction, CHMP5 helps assemble or tune LIP5/VPS4 activity on ESCRT-III substrates, supporting MVB cargo sorting, ESCRT-III complex disassembly, and downstream lysosomal degradation of ubiquitinated/endocytosed cargo relevant to proteostasis. in_complex: id: GO:0000815 label: ESCRT III complex directly_involved_in: - id: GO:0071985 label: multivesicular body sorting pathway - id: GO:0036258 label: multivesicular body assembly - id: GO:1904903 label: ESCRT III complex disassembly - id: GO:0043162 label: ubiquitin-dependent protein catabolic process via the multivesicular body sorting pathway - id: GO:1902774 label: late endosome to lysosome transport locations: - id: GO:0010008 label: endosome membrane - id: GO:0032585 label: multivesicular body membrane supported_by: - reference_id: UniProt:Q9NZZ3 supporting_text: involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs - reference_id: PMID:15644320 supporting_text: both LIP5 and CHMP5 function in MVB sorting - reference_id: PMID:15644320 supporting_text: Depletion of CHMP5 by siRNA does not affect the distribution or morphology of early endosomes, lysosomes, or Golgi but does result in reduced degradation of the EGFR - reference_id: file:human/CHMP5/CHMP5-notes.md supporting_text: 'Core: ESCRT-III complex membership, MVB sorting/assembly, ubiquitin-dependent cargo degradation through MVB sorting, ESCRT-III disassembly/recycling via LIP5/VTA1 and VPS4, and the endolysosomal degradation route that follows MVB sorting.' - reference_id: PMID:18385515 supporting_text: LIP5 binds preferentially to soluble CHMP5 - reference_id: PMID:18385515 supporting_text: These studies point to a role for direct binding between LIP5 and ESCRT-III proteins - reference_id: PMID:23105106 supporting_text: promoting assembly of active VPS4 enzymes on the polymeric ESCRT-III substrate - reference_id: PMID:23105106 supporting_text: formation of stable VPS4 complexes with both LIP5 and CHMP5 requires LIP5 to bind both a MIM1-containing ESCRT-III protein and CHMP5 - reference_id: file:human/CHMP5/CHMP5-notes.md supporting_text: The mechanistic refinement is that CHMP5 binds LIP5/VTA1 and helps regulate VPS4 activation/disassembly of ESCRT-III rather than acting as a CHMP4/Snf7-like primary filament/scission subunit. - reference_id: UniProt:Q9NZZ3 supporting_text: Probable peripherally associated component of the endosomal sorting required for transport complex III (ESCRT-III) - reference_id: PMID:16730941 supporting_text: known components of the human ESCRT III complex - reference_id: PMID:23105106 supporting_text: the ESCRT-III and VPS4 ATPase complexes catalyze the membrane fission events associated with these processes - reference_id: file:human/CHMP5/CHMP5-notes.md supporting_text: CHMP5 (UniProt Q9NZZ3) is a SNF7/ESCRT-III family protein best treated as an ESCRT-III regulatory component for endosomal MVB sorting and VPS4/LIP5-mediated ESCRT-III recycling. - reference_id: UniProt:Q9NZZ3 supporting_text: enabling degradation of membrane proteins, such as stimulated growth factor receptors - reference_id: PMID:15644320 supporting_text: reduced degradation of the EGFR similar to silencing of LIP5 - reference_id: PMID:17984323 supporting_text: Functional multivesicular bodies are required for autophagic clearance - reference_id: file:human/CHMP5/CHMP5-notes.md supporting_text: 'Proteostasis-network context: CHMP5 supports endolysosomal degradation through ESCRT/MVB sorting' proposed_new_terms: [] suggested_questions: - question: Can endogenous CHMP5 depletion/rescue separate its direct LIP5/VTA1-VPS4 regulatory role from pathway-level ESCRT-III membrane-fission annotations? - question: Which CHMP5-specific autophagy annotations are supported by direct autophagosome closure or maturation assays rather than by ESCRT complex membership? - question: Should viral-budding annotations for CHMP5 be replaced by a regulatory or non-core context, given evidence that CHMP5 depletion increases HIV-1 release while LIP5 is required? suggested_experiments: - description: Perform acute endogenous CHMP5 depletion and rescue with wild-type, LIP5-binding-defective, and ESCRT-tail mutant CHMP5 while measuring EGFR degradation, MVB ILV cargo sorting, and VPS4 recruitment/disassembly dynamics. hypothesis: CHMP5 rescue of MVB cargo degradation will require its LIP5/VTA1 interaction and will primarily affect VPS4-mediated ESCRT-III recycling rather than initial cargo recognition. - description: Test CHMP5 recruitment and requirement in starvation autophagy, mitophagy, and xenophagy assays using direct reporters for unsealed autophagosomes and autolysosome formation. hypothesis: CHMP5 will contribute to autophagic clearance through endolysosomal/MVB function and pathogen-specific xenophagy contexts, but may not be a general autophagosome sealing effector. - description: Compare CHMP5 and LIP5 knockdown/rescue in HIV-1 budding assays while quantifying MVB cargo degradation in parallel. hypothesis: CHMP5 perturbation will distinguish MVB sorting from viral release, supporting curation of viral budding as non-core or over-annotated for CHMP5.