CHMP5

Existing Annotations Review

GO Term	Evidence	Action	Reason
GO:0005635 nuclear envelope	IBA GO_REF:0000033	KEEP AS NON CORE	Summary: Plausible non-core ESCRT nuclear-envelope context for CHMP5: nuclear envelope. 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. Supporting Evidence: PMID:26040712 ESCRT-III, VPS4 and spastin cooperate to coordinate nuclear envelope sealing and spindle disassembly PMID:26040713 ESCRT-III controls nuclear envelope reformation file:human/CHMP5/CHMP5-notes.md Secondary ESCRT contexts should generally be kept as non-core.
GO:0031468 nuclear membrane reassembly	IBA GO_REF:0000033	KEEP AS NON CORE	Summary: Plausible non-core ESCRT nuclear-envelope context for CHMP5: nuclear membrane reassembly. 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. Supporting Evidence: PMID:26040712 ESCRT-III, VPS4 and spastin cooperate to coordinate nuclear envelope sealing and spindle disassembly PMID:26040713 ESCRT-III controls nuclear envelope reformation file:human/CHMP5/CHMP5-notes.md Secondary ESCRT contexts should generally be kept as non-core.
GO:0000815 ESCRT III complex	IBA GO_REF:0000033	ACCEPT	Summary: Supported core CHMP5 ESCRT-III complex membership: ESCRT III complex. 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. Supporting Evidence: UniProt:Q9NZZ3 Probable peripherally associated component of the endosomal sorting required for transport complex III (ESCRT-III) PMID:16730941 known components of the human ESCRT III complex PMID:23105106 the ESCRT-III and VPS4 ATPase complexes catalyze the membrane fission events associated with these processes file:human/CHMP5/CHMP5-notes.md 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. PMID:18385515 LIP5 binds preferentially to soluble CHMP5 PMID:18385515 These studies point to a role for direct binding between LIP5 and ESCRT-III proteins PMID:23105106 promoting assembly of active VPS4 enzymes on the polymeric ESCRT-III substrate PMID:23105106 formation of stable VPS4 complexes with both LIP5 and CHMP5 requires LIP5 to bind both a MIM1-containing ESCRT-III protein and CHMP5 file:human/CHMP5/CHMP5-notes.md 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.
GO:0032511 late endosome to vacuole transport via multivesicular body sorting pathway	IBA GO_REF:0000033	MODIFY	Summary: The MVB-sorting essence is correct, but the human CHMP5 annotation should use the direct MVB sorting term. 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. Proposed replacements: multivesicular body sorting pathway late endosome to lysosome transport Supporting Evidence: UniProt:Q9NZZ3 involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs PMID:15644320 both LIP5 and CHMP5 function in MVB sorting PMID:15644320 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 file:human/CHMP5/CHMP5-notes.md 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. UniProt:Q9NZZ3 enabling degradation of membrane proteins, such as stimulated growth factor receptors PMID:15644320 reduced degradation of the EGFR similar to silencing of LIP5 PMID:17984323 Functional multivesicular bodies are required for autophagic clearance file:human/CHMP5/CHMP5-notes.md Proteostasis-network context: CHMP5 supports endolysosomal degradation through ESCRT/MVB sorting
GO:0000776 kinetochore	IEA GO_REF:0000117	KEEP AS NON CORE	Summary: Plausible non-core ESCRT cell-cycle/centrosome context for CHMP5: kinetochore. 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. Supporting Evidence: PMID:20616062 depletion of VPS4A, VPS4B, or any of the 11 different human ESCRT-III (CHMP) proteins inhibited abscission PMID:20616062 producing multipolar spindles (most ESCRT-III/VPS4 proteins) or monopolar spindles (CHMP2A or CHMP5) PMID:20616062 ESCRT-III/VPS4 proteins function at centrosomes to help regulate their maintenance or proliferation and then at midbodies during abscission file:human/CHMP5/CHMP5-notes.md Secondary ESCRT contexts should generally be kept as non-core.
GO:0001778 plasma membrane repair	IEA GO_REF:0000117	KEEP AS NON CORE	Summary: Plausible non-core CHMP5 plasma membrane repair ESCRT context. Reason: Plasma membrane repair is a valid ESCRT pathway output, but the available CHMP5-specific evidence does not make it the core CHMP5 function. Supporting Evidence: PMID:24482116 ESCRT proteins were recruited within seconds to plasma membrane wounds PMID:24482116 repair of certain wounds is ensured by ESCRT-mediated extracellular shedding of wounded portions file:human/CHMP5/CHMP5-notes.md Secondary ESCRT contexts should generally be kept as non-core.
GO:0005643 nuclear pore	IEA GO_REF:0000117	KEEP AS NON CORE	Summary: Plausible non-core ESCRT nuclear-envelope context for CHMP5: nuclear pore. 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. Supporting Evidence: PMID:26040712 ESCRT-III, VPS4 and spastin cooperate to coordinate nuclear envelope sealing and spindle disassembly PMID:26040713 ESCRT-III controls nuclear envelope reformation file:human/CHMP5/CHMP5-notes.md Secondary ESCRT contexts should generally be kept as non-core.
GO:0005765 lysosomal membrane	IEA GO_REF:0000117	KEEP AS NON CORE	Summary: Plausible PN-relevant but non-core CHMP5 autophagy/endolysosomal context: lysosomal membrane. 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. Supporting Evidence: PMID:17984323 Functional multivesicular bodies are required for autophagic clearance PMID:17984323 functional MVBs are required to prevent accumulation of abnormal proteins PMID:30061757 CHMP5-one of the IcsB targets and a component of the ESCRT-III complex-specifically affected S. flexneri escape from host autophagy. file:human/CHMP5/CHMP5-notes.md the cached CHMP5 GOA autophagy annotations mostly derive from ESCRT-complex context rather than CHMP5-specific autophagosome sealing assays
GO:0005828 kinetochore microtubule	IEA GO_REF:0000117	KEEP AS NON CORE	Summary: Plausible non-core ESCRT cell-cycle/centrosome context for CHMP5: kinetochore microtubule. 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. Supporting Evidence: PMID:20616062 depletion of VPS4A, VPS4B, or any of the 11 different human ESCRT-III (CHMP) proteins inhibited abscission PMID:20616062 producing multipolar spindles (most ESCRT-III/VPS4 proteins) or monopolar spindles (CHMP2A or CHMP5) PMID:20616062 ESCRT-III/VPS4 proteins function at centrosomes to help regulate their maintenance or proliferation and then at midbodies during abscission file:human/CHMP5/CHMP5-notes.md Secondary ESCRT contexts should generally be kept as non-core.
GO:0005829 cytosol	IEA GO_REF:0000044	KEEP AS NON CORE	Summary: True or plausible broad CHMP5 location: cytosol. Reason: CHMP5 is primarily cytosolic and can be detected in broad compartments, but broad locations do not define the core function. Supporting Evidence: UniProt:Q9NZZ3 Cytoplasm, cytosol PMID:15644320 We identify CHMP5 as a LIP5-binding protein and show that CHMP5 is primarily cytosolic. file:human/CHMP5/CHMP5-notes.md Non-core: cytosol/nucleus/exosome locations, midbody/cytokinesis, spindle/centrosome, nuclear envelope/pore reassembly, plasma membrane repair, infection/autophagy contexts, and viral budding.
GO:0007034 vacuolar transport	IEA GO_REF:0000002	MODIFY	Summary: Vacuolar transport is too broad for CHMP5 and should be represented as MVB sorting. Reason: The conserved ESCRT biology is cargo sorting into MVBs followed by lysosomal delivery, not generic vacuolar transport. Proposed replacements: multivesicular body sorting pathway Supporting Evidence: UniProt:Q9NZZ3 involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs PMID:15644320 both LIP5 and CHMP5 function in MVB sorting PMID:15644320 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 file:human/CHMP5/CHMP5-notes.md 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.
GO:0007080 mitotic metaphase chromosome alignment	IEA GO_REF:0000117	KEEP AS NON CORE	Summary: Plausible non-core ESCRT cell-cycle/centrosome context for CHMP5: mitotic metaphase chromosome alignment. 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. Supporting Evidence: PMID:20616062 depletion of VPS4A, VPS4B, or any of the 11 different human ESCRT-III (CHMP) proteins inhibited abscission PMID:20616062 producing multipolar spindles (most ESCRT-III/VPS4 proteins) or monopolar spindles (CHMP2A or CHMP5) PMID:20616062 ESCRT-III/VPS4 proteins function at centrosomes to help regulate their maintenance or proliferation and then at midbodies during abscission file:human/CHMP5/CHMP5-notes.md Secondary ESCRT contexts should generally be kept as non-core.
GO:0010008 endosome membrane	IEA GO_REF:0000044	ACCEPT	Summary: Supported CHMP5 endosomal/MVB membrane context: endosome membrane. 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. Supporting Evidence: UniProt:Q9NZZ3 involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs PMID:15644320 both LIP5 and CHMP5 function in MVB sorting PMID:15644320 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 file:human/CHMP5/CHMP5-notes.md 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. UniProt:Q9NZZ3 Probable peripherally associated component of the endosomal sorting required for transport complex III (ESCRT-III) PMID:16730941 known components of the human ESCRT III complex PMID:23105106 the ESCRT-III and VPS4 ATPase complexes catalyze the membrane fission events associated with these processes file:human/CHMP5/CHMP5-notes.md 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.
GO:0030496 midbody	IEA GO_REF:0000120	KEEP AS NON CORE	Summary: Plausible non-core ESCRT cell-cycle/centrosome context for CHMP5: midbody. 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. Supporting Evidence: PMID:20616062 depletion of VPS4A, VPS4B, or any of the 11 different human ESCRT-III (CHMP) proteins inhibited abscission PMID:20616062 producing multipolar spindles (most ESCRT-III/VPS4 proteins) or monopolar spindles (CHMP2A or CHMP5) PMID:20616062 ESCRT-III/VPS4 proteins function at centrosomes to help regulate their maintenance or proliferation and then at midbodies during abscission file:human/CHMP5/CHMP5-notes.md Secondary ESCRT contexts should generally be kept as non-core.
GO:0031468 nuclear membrane reassembly	IEA GO_REF:0000117	KEEP AS NON CORE	Summary: Plausible non-core ESCRT nuclear-envelope context for CHMP5: nuclear membrane reassembly. 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. Supporting Evidence: PMID:26040712 ESCRT-III, VPS4 and spastin cooperate to coordinate nuclear envelope sealing and spindle disassembly PMID:26040713 ESCRT-III controls nuclear envelope reformation file:human/CHMP5/CHMP5-notes.md Secondary ESCRT contexts should generally be kept as non-core.
GO:0032585 multivesicular body membrane	IEA GO_REF:0000117	ACCEPT	Summary: Supported CHMP5 endosomal/MVB membrane context: multivesicular body membrane. 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. Supporting Evidence: UniProt:Q9NZZ3 involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs PMID:15644320 both LIP5 and CHMP5 function in MVB sorting PMID:15644320 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 file:human/CHMP5/CHMP5-notes.md 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. UniProt:Q9NZZ3 Probable peripherally associated component of the endosomal sorting required for transport complex III (ESCRT-III) PMID:16730941 known components of the human ESCRT III complex PMID:23105106 the ESCRT-III and VPS4 ATPase complexes catalyze the membrane fission events associated with these processes file:human/CHMP5/CHMP5-notes.md 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.
GO:0039702 viral budding via host ESCRT complex	IEA GO_REF:0000117	MARK AS OVER ANNOTATED	Summary: Viral budding is not a core CHMP5 cellular function and is likely over-annotated here: viral budding via host ESCRT complex. 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. Supporting Evidence: PMID:15644320 CHMP5 depletion results in an increase in the release of infectious HIV-1 particles PMID:15644320 both LIP5 and CHMP5 function in MVB sorting, whereas only LIP5 is required for HIV release. file:human/CHMP5/CHMP5-notes.md 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.
GO:0043162 ubiquitin-dependent protein catabolic process via the multivesicular body sorting pathway	IEA GO_REF:0000117	ACCEPT	Summary: Supported core CHMP5 MVB/endolysosomal sorting annotation: ubiquitin-dependent protein catabolic process via the multivesicular body sorting pathway. 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. Supporting Evidence: UniProt:Q9NZZ3 involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs PMID:15644320 both LIP5 and CHMP5 function in MVB sorting PMID:15644320 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 file:human/CHMP5/CHMP5-notes.md 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. UniProt:Q9NZZ3 enabling degradation of membrane proteins, such as stimulated growth factor receptors PMID:15644320 reduced degradation of the EGFR similar to silencing of LIP5 PMID:17984323 Functional multivesicular bodies are required for autophagic clearance file:human/CHMP5/CHMP5-notes.md Proteostasis-network context: CHMP5 supports endolysosomal degradation through ESCRT/MVB sorting
GO:0046761 viral budding from plasma membrane	IEA GO_REF:0000117	MARK AS OVER ANNOTATED	Summary: Viral budding is not a core CHMP5 cellular function and is likely over-annotated here: viral budding from plasma membrane. 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. Supporting Evidence: PMID:15644320 CHMP5 depletion results in an increase in the release of infectious HIV-1 particles PMID:15644320 both LIP5 and CHMP5 function in MVB sorting, whereas only LIP5 is required for HIV release. file:human/CHMP5/CHMP5-notes.md 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.
GO:0061952 midbody abscission	IEA GO_REF:0000117	KEEP AS NON CORE	Summary: Plausible non-core ESCRT cell-cycle/centrosome context for CHMP5: midbody abscission. 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. Supporting Evidence: PMID:20616062 depletion of VPS4A, VPS4B, or any of the 11 different human ESCRT-III (CHMP) proteins inhibited abscission PMID:20616062 producing multipolar spindles (most ESCRT-III/VPS4 proteins) or monopolar spindles (CHMP2A or CHMP5) PMID:20616062 ESCRT-III/VPS4 proteins function at centrosomes to help regulate their maintenance or proliferation and then at midbodies during abscission file:human/CHMP5/CHMP5-notes.md Secondary ESCRT contexts should generally be kept as non-core.
GO:0071985 multivesicular body sorting pathway	IEA GO_REF:0000117	ACCEPT	Summary: Supported core CHMP5 MVB/endolysosomal sorting annotation: multivesicular body sorting pathway. 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. Supporting Evidence: UniProt:Q9NZZ3 involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs PMID:15644320 both LIP5 and CHMP5 function in MVB sorting PMID:15644320 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 file:human/CHMP5/CHMP5-notes.md 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. UniProt:Q9NZZ3 enabling degradation of membrane proteins, such as stimulated growth factor receptors PMID:15644320 reduced degradation of the EGFR similar to silencing of LIP5 PMID:17984323 Functional multivesicular bodies are required for autophagic clearance file:human/CHMP5/CHMP5-notes.md Proteostasis-network context: CHMP5 supports endolysosomal degradation through ESCRT/MVB sorting
GO:0097352 autophagosome maturation	IEA GO_REF:0000117	KEEP AS NON CORE	Summary: Plausible PN-relevant but non-core CHMP5 autophagy/endolysosomal context: autophagosome maturation. 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. Supporting Evidence: PMID:17984323 Functional multivesicular bodies are required for autophagic clearance PMID:17984323 functional MVBs are required to prevent accumulation of abnormal proteins PMID:30061757 CHMP5-one of the IcsB targets and a component of the ESCRT-III complex-specifically affected S. flexneri escape from host autophagy. file:human/CHMP5/CHMP5-notes.md the cached CHMP5 GOA autophagy annotations mostly derive from ESCRT-complex context rather than CHMP5-specific autophagosome sealing assays
GO:1901673 regulation of mitotic spindle assembly	IEA GO_REF:0000117	KEEP AS NON CORE	Summary: Plausible non-core ESCRT cell-cycle/centrosome context for CHMP5: regulation of mitotic spindle assembly. 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. Supporting Evidence: PMID:20616062 depletion of VPS4A, VPS4B, or any of the 11 different human ESCRT-III (CHMP) proteins inhibited abscission PMID:20616062 producing multipolar spindles (most ESCRT-III/VPS4 proteins) or monopolar spindles (CHMP2A or CHMP5) PMID:20616062 ESCRT-III/VPS4 proteins function at centrosomes to help regulate their maintenance or proliferation and then at midbodies during abscission file:human/CHMP5/CHMP5-notes.md Secondary ESCRT contexts should generally be kept as non-core.
GO:1902774 late endosome to lysosome transport	IEA GO_REF:0000117	ACCEPT	Summary: Supported CHMP5 endolysosomal degradation route annotation. 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. Supporting Evidence: UniProt:Q9NZZ3 involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs PMID:15644320 both LIP5 and CHMP5 function in MVB sorting PMID:15644320 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 file:human/CHMP5/CHMP5-notes.md 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. UniProt:Q9NZZ3 enabling degradation of membrane proteins, such as stimulated growth factor receptors PMID:15644320 reduced degradation of the EGFR similar to silencing of LIP5 PMID:17984323 Functional multivesicular bodies are required for autophagic clearance file:human/CHMP5/CHMP5-notes.md Proteostasis-network context: CHMP5 supports endolysosomal degradation through ESCRT/MVB sorting
GO:1904930 amphisome membrane	IEA GO_REF:0000117	KEEP AS NON CORE	Summary: Plausible PN-relevant but non-core CHMP5 autophagy/endolysosomal context: amphisome membrane. 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. Supporting Evidence: PMID:17984323 Functional multivesicular bodies are required for autophagic clearance PMID:17984323 functional MVBs are required to prevent accumulation of abnormal proteins PMID:30061757 CHMP5-one of the IcsB targets and a component of the ESCRT-III complex-specifically affected S. flexneri escape from host autophagy. file:human/CHMP5/CHMP5-notes.md the cached CHMP5 GOA autophagy annotations mostly derive from ESCRT-complex context rather than CHMP5-specific autophagosome sealing assays
GO:0005515 protein binding	IPI PMID:16730941 A systematic analysis of human CHMP protein interactions: ad...	MARK AS OVER ANNOTATED	Summary: Generic protein binding does not capture the specific CHMP5/LIP5/VPS4-ESCRT regulatory mechanism. 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. Supporting Evidence: PMID:15644320 We identify CHMP5 as a LIP5-binding protein and show that CHMP5 is primarily cytosolic. PMID:18385515 LIP5 binds preferentially to soluble CHMP5 PMID:23105106 the second LIP5 MIT module binds with unusually high affinity to a novel MIM element within the ESCRT-III protein CHMP5 file:human/CHMP5/CHMP5-notes.md 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.
GO:0005515 protein binding	IPI PMID:17711858 The MIT domain of UBPY constitutes a CHMP binding and endoso...	MARK AS OVER ANNOTATED	Summary: Generic protein binding does not capture the specific CHMP5/LIP5/VPS4-ESCRT regulatory mechanism. 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. Supporting Evidence: PMID:15644320 We identify CHMP5 as a LIP5-binding protein and show that CHMP5 is primarily cytosolic. PMID:18385515 LIP5 binds preferentially to soluble CHMP5 PMID:23105106 the second LIP5 MIT module binds with unusually high affinity to a novel MIM element within the ESCRT-III protein CHMP5 file:human/CHMP5/CHMP5-notes.md 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.
GO:0005515 protein binding	IPI PMID:21988832 Toward an understanding of the protein interaction network o...	MARK AS OVER ANNOTATED	Summary: Generic protein binding does not capture the specific CHMP5/LIP5/VPS4-ESCRT regulatory mechanism. 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. Supporting Evidence: PMID:15644320 We identify CHMP5 as a LIP5-binding protein and show that CHMP5 is primarily cytosolic. PMID:18385515 LIP5 binds preferentially to soluble CHMP5 PMID:23105106 the second LIP5 MIT module binds with unusually high affinity to a novel MIM element within the ESCRT-III protein CHMP5 file:human/CHMP5/CHMP5-notes.md 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.
GO:0005515 protein binding	IPI PMID:25416956 A proteome-scale map of the human interactome network.	MARK AS OVER ANNOTATED	Summary: Generic protein binding does not capture the specific CHMP5/LIP5/VPS4-ESCRT regulatory mechanism. 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. Supporting Evidence: PMID:15644320 We identify CHMP5 as a LIP5-binding protein and show that CHMP5 is primarily cytosolic. PMID:18385515 LIP5 binds preferentially to soluble CHMP5 PMID:23105106 the second LIP5 MIT module binds with unusually high affinity to a novel MIM element within the ESCRT-III protein CHMP5 file:human/CHMP5/CHMP5-notes.md 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.
GO:0005515 protein binding	IPI PMID:26496610 A human interactome in three quantitative dimensions organiz...	MARK AS OVER ANNOTATED	Summary: Generic protein binding does not capture the specific CHMP5/LIP5/VPS4-ESCRT regulatory mechanism. 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. Supporting Evidence: PMID:15644320 We identify CHMP5 as a LIP5-binding protein and show that CHMP5 is primarily cytosolic. PMID:18385515 LIP5 binds preferentially to soluble CHMP5 PMID:23105106 the second LIP5 MIT module binds with unusually high affinity to a novel MIM element within the ESCRT-III protein CHMP5 file:human/CHMP5/CHMP5-notes.md 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.
GO:0005515 protein binding	IPI PMID:27812135 Characterization and Genetic Analyses of New Genes Coding fo...	MARK AS OVER ANNOTATED	Summary: Generic protein binding does not capture the specific CHMP5/LIP5/VPS4-ESCRT regulatory mechanism. 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. Supporting Evidence: PMID:27812135 The primary interaction was confirmed by coimmunoprecipitation and/or bioluminescence resonance energy transfer (BRET) experiments for 11 of these proteins PMID:27812135 CHMP5ESCRTIII proteins are required for late MVB formation and their fusion with the lysosome file:human/CHMP5/CHMP5-notes.md The NOD2/LPS/MDP annotations are not core CHMP5 function. file:human/CHMP5/CHMP5-notes.md the study itself says these new interacting proteins did not appear to be major NOD2-dependent NF-kappaB regulators in the assay
GO:0005515 protein binding	IPI PMID:28514442 Architecture of the human interactome defines protein commun...	MARK AS OVER ANNOTATED	Summary: Generic protein binding does not capture the specific CHMP5/LIP5/VPS4-ESCRT regulatory mechanism. 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. Supporting Evidence: PMID:15644320 We identify CHMP5 as a LIP5-binding protein and show that CHMP5 is primarily cytosolic. PMID:18385515 LIP5 binds preferentially to soluble CHMP5 PMID:23105106 the second LIP5 MIT module binds with unusually high affinity to a novel MIM element within the ESCRT-III protein CHMP5 file:human/CHMP5/CHMP5-notes.md 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.
GO:0005515 protein binding	IPI PMID:32296183 A reference map of the human binary protein interactome.	MARK AS OVER ANNOTATED	Summary: Generic protein binding does not capture the specific CHMP5/LIP5/VPS4-ESCRT regulatory mechanism. 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. Supporting Evidence: PMID:15644320 We identify CHMP5 as a LIP5-binding protein and show that CHMP5 is primarily cytosolic. PMID:18385515 LIP5 binds preferentially to soluble CHMP5 PMID:23105106 the second LIP5 MIT module binds with unusually high affinity to a novel MIM element within the ESCRT-III protein CHMP5 file:human/CHMP5/CHMP5-notes.md 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.
GO:0005515 protein binding	IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling...	MARK AS OVER ANNOTATED	Summary: Generic protein binding does not capture the specific CHMP5/LIP5/VPS4-ESCRT regulatory mechanism. 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. Supporting Evidence: PMID:15644320 We identify CHMP5 as a LIP5-binding protein and show that CHMP5 is primarily cytosolic. PMID:18385515 LIP5 binds preferentially to soluble CHMP5 PMID:23105106 the second LIP5 MIT module binds with unusually high affinity to a novel MIM element within the ESCRT-III protein CHMP5 file:human/CHMP5/CHMP5-notes.md 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.
GO:0005634 nucleus	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: True or plausible broad CHMP5 location: nucleus. Reason: CHMP5 is primarily cytosolic and can be detected in broad compartments, but broad locations do not define the core function. Supporting Evidence: UniProt:Q9NZZ3 Cytoplasm, cytosol PMID:15644320 We identify CHMP5 as a LIP5-binding protein and show that CHMP5 is primarily cytosolic. file:human/CHMP5/CHMP5-notes.md Non-core: cytosol/nucleus/exosome locations, midbody/cytokinesis, spindle/centrosome, nuclear envelope/pore reassembly, plasma membrane repair, infection/autophagy contexts, and viral budding.
GO:0005829 cytosol	IDA GO_REF:0000052	KEEP AS NON CORE	Summary: True or plausible broad CHMP5 location: cytosol. Reason: CHMP5 is primarily cytosolic and can be detected in broad compartments, but broad locations do not define the core function. Supporting Evidence: UniProt:Q9NZZ3 Cytoplasm, cytosol PMID:15644320 We identify CHMP5 as a LIP5-binding protein and show that CHMP5 is primarily cytosolic. file:human/CHMP5/CHMP5-notes.md Non-core: cytosol/nucleus/exosome locations, midbody/cytokinesis, spindle/centrosome, nuclear envelope/pore reassembly, plasma membrane repair, infection/autophagy contexts, and viral budding.
GO:0015630 microtubule cytoskeleton	IDA GO_REF:0000052	KEEP AS NON CORE	Summary: Plausible non-core ESCRT cell-cycle/centrosome context for CHMP5: microtubule cytoskeleton. 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. Supporting Evidence: PMID:20616062 depletion of VPS4A, VPS4B, or any of the 11 different human ESCRT-III (CHMP) proteins inhibited abscission PMID:20616062 producing multipolar spindles (most ESCRT-III/VPS4 proteins) or monopolar spindles (CHMP2A or CHMP5) PMID:20616062 ESCRT-III/VPS4 proteins function at centrosomes to help regulate their maintenance or proliferation and then at midbodies during abscission file:human/CHMP5/CHMP5-notes.md Secondary ESCRT contexts should generally be kept as non-core.
GO:0030496 midbody	IDA GO_REF:0000052	KEEP AS NON CORE	Summary: Plausible non-core ESCRT cell-cycle/centrosome context for CHMP5: midbody. 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. Supporting Evidence: PMID:20616062 depletion of VPS4A, VPS4B, or any of the 11 different human ESCRT-III (CHMP) proteins inhibited abscission PMID:20616062 producing multipolar spindles (most ESCRT-III/VPS4 proteins) or monopolar spindles (CHMP2A or CHMP5) PMID:20616062 ESCRT-III/VPS4 proteins function at centrosomes to help regulate their maintenance or proliferation and then at midbodies during abscission file:human/CHMP5/CHMP5-notes.md Secondary ESCRT contexts should generally be kept as non-core.
GO:0000421 autophagosome membrane	IDA PMID:17984323 Functional multivesicular bodies are required for autophagic...	KEEP AS NON CORE	Summary: Plausible PN-relevant but non-core CHMP5 autophagy/endolysosomal context: autophagosome membrane. 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. Supporting Evidence: PMID:17984323 Functional multivesicular bodies are required for autophagic clearance PMID:17984323 functional MVBs are required to prevent accumulation of abnormal proteins PMID:30061757 CHMP5-one of the IcsB targets and a component of the ESCRT-III complex-specifically affected S. flexneri escape from host autophagy. file:human/CHMP5/CHMP5-notes.md the cached CHMP5 GOA autophagy annotations mostly derive from ESCRT-complex context rather than CHMP5-specific autophagosome sealing assays
GO:0000776 kinetochore	IDA PMID:26040712 Spastin and ESCRT-III coordinate mitotic spindle disassembly...	KEEP AS NON CORE	Summary: Plausible non-core ESCRT cell-cycle/centrosome context for CHMP5: kinetochore. 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. Supporting Evidence: PMID:20616062 depletion of VPS4A, VPS4B, or any of the 11 different human ESCRT-III (CHMP) proteins inhibited abscission PMID:20616062 producing multipolar spindles (most ESCRT-III/VPS4 proteins) or monopolar spindles (CHMP2A or CHMP5) PMID:20616062 ESCRT-III/VPS4 proteins function at centrosomes to help regulate their maintenance or proliferation and then at midbodies during abscission file:human/CHMP5/CHMP5-notes.md Secondary ESCRT contexts should generally be kept as non-core.
GO:0000815 ESCRT III complex	NAS PMID:36107470 Comprehensive analysis of the human ESCRT-III-MIT domain int...	ACCEPT	Summary: Supported core CHMP5 ESCRT-III complex membership: ESCRT III complex. 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. Supporting Evidence: UniProt:Q9NZZ3 Probable peripherally associated component of the endosomal sorting required for transport complex III (ESCRT-III) PMID:16730941 known components of the human ESCRT III complex PMID:23105106 the ESCRT-III and VPS4 ATPase complexes catalyze the membrane fission events associated with these processes file:human/CHMP5/CHMP5-notes.md 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. PMID:18385515 LIP5 binds preferentially to soluble CHMP5 PMID:18385515 These studies point to a role for direct binding between LIP5 and ESCRT-III proteins PMID:23105106 promoting assembly of active VPS4 enzymes on the polymeric ESCRT-III substrate PMID:23105106 formation of stable VPS4 complexes with both LIP5 and CHMP5 requires LIP5 to bind both a MIM1-containing ESCRT-III protein and CHMP5 file:human/CHMP5/CHMP5-notes.md 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.
GO:0001778 plasma membrane repair	IDA PMID:24482116 ESCRT machinery is required for plasma membrane repair.	KEEP AS NON CORE	Summary: Plausible non-core CHMP5 plasma membrane repair ESCRT context. Reason: Plasma membrane repair is a valid ESCRT pathway output, but the available CHMP5-specific evidence does not make it the core CHMP5 function. Supporting Evidence: PMID:24482116 ESCRT proteins were recruited within seconds to plasma membrane wounds PMID:24482116 repair of certain wounds is ensured by ESCRT-mediated extracellular shedding of wounded portions file:human/CHMP5/CHMP5-notes.md Secondary ESCRT contexts should generally be kept as non-core.
GO:0005643 nuclear pore	IDA PMID:26040713 ESCRT-III controls nuclear envelope reformation.	KEEP AS NON CORE	Summary: Plausible non-core ESCRT nuclear-envelope context for CHMP5: nuclear pore. 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. Supporting Evidence: PMID:26040712 ESCRT-III, VPS4 and spastin cooperate to coordinate nuclear envelope sealing and spindle disassembly PMID:26040713 ESCRT-III controls nuclear envelope reformation file:human/CHMP5/CHMP5-notes.md Secondary ESCRT contexts should generally be kept as non-core.
GO:0005765 lysosomal membrane	IDA PMID:17984323 Functional multivesicular bodies are required for autophagic...	KEEP AS NON CORE	Summary: Plausible PN-relevant but non-core CHMP5 autophagy/endolysosomal context: lysosomal membrane. 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. Supporting Evidence: PMID:17984323 Functional multivesicular bodies are required for autophagic clearance PMID:17984323 functional MVBs are required to prevent accumulation of abnormal proteins PMID:30061757 CHMP5-one of the IcsB targets and a component of the ESCRT-III complex-specifically affected S. flexneri escape from host autophagy. file:human/CHMP5/CHMP5-notes.md the cached CHMP5 GOA autophagy annotations mostly derive from ESCRT-complex context rather than CHMP5-specific autophagosome sealing assays
GO:0005828 kinetochore microtubule	IDA PMID:26040712 Spastin and ESCRT-III coordinate mitotic spindle disassembly...	KEEP AS NON CORE	Summary: Plausible non-core ESCRT cell-cycle/centrosome context for CHMP5: kinetochore microtubule. 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. Supporting Evidence: PMID:20616062 depletion of VPS4A, VPS4B, or any of the 11 different human ESCRT-III (CHMP) proteins inhibited abscission PMID:20616062 producing multipolar spindles (most ESCRT-III/VPS4 proteins) or monopolar spindles (CHMP2A or CHMP5) PMID:20616062 ESCRT-III/VPS4 proteins function at centrosomes to help regulate their maintenance or proliferation and then at midbodies during abscission file:human/CHMP5/CHMP5-notes.md Secondary ESCRT contexts should generally be kept as non-core.
GO:0005886 plasma membrane	IDA PMID:24878737 Structure of cellular ESCRT-III spirals and their relationsh...	KEEP AS NON CORE	Summary: Supported but non-core plasma membrane ESCRT context for CHMP5. Reason: Plasma membrane localization in ESCRT/HIV or repair assays is a secondary pathway context and not the main CHMP5 proteostasis function. Supporting Evidence: PMID:15644320 CHMP5 depletion results in an increase in the release of infectious HIV-1 particles PMID:15644320 both LIP5 and CHMP5 function in MVB sorting, whereas only LIP5 is required for HIV release. file:human/CHMP5/CHMP5-notes.md 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. PMID:24482116 ESCRT proteins were recruited within seconds to plasma membrane wounds PMID:24482116 repair of certain wounds is ensured by ESCRT-mediated extracellular shedding of wounded portions file:human/CHMP5/CHMP5-notes.md Secondary ESCRT contexts should generally be kept as non-core.
GO:0006914 autophagy	IMP PMID:17984323 Functional multivesicular bodies are required for autophagic...	KEEP AS NON CORE	Summary: Plausible PN-relevant but non-core CHMP5 autophagy/endolysosomal context: autophagy. 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. Supporting Evidence: PMID:17984323 Functional multivesicular bodies are required for autophagic clearance PMID:17984323 functional MVBs are required to prevent accumulation of abnormal proteins PMID:30061757 CHMP5-one of the IcsB targets and a component of the ESCRT-III complex-specifically affected S. flexneri escape from host autophagy. file:human/CHMP5/CHMP5-notes.md the cached CHMP5 GOA autophagy annotations mostly derive from ESCRT-complex context rather than CHMP5-specific autophagosome sealing assays
GO:0006997 nucleus organization	IMP PMID:20616062 Human ESCRT-III and VPS4 proteins are required for centrosom...	KEEP AS NON CORE	Summary: Plausible non-core ESCRT cell-cycle/centrosome context for CHMP5: nucleus organization. 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. Supporting Evidence: PMID:20616062 depletion of VPS4A, VPS4B, or any of the 11 different human ESCRT-III (CHMP) proteins inhibited abscission PMID:20616062 producing multipolar spindles (most ESCRT-III/VPS4 proteins) or monopolar spindles (CHMP2A or CHMP5) PMID:20616062 ESCRT-III/VPS4 proteins function at centrosomes to help regulate their maintenance or proliferation and then at midbodies during abscission file:human/CHMP5/CHMP5-notes.md Secondary ESCRT contexts should generally be kept as non-core.
GO:0007080 mitotic metaphase chromosome alignment	IMP PMID:20616062 Human ESCRT-III and VPS4 proteins are required for centrosom...	KEEP AS NON CORE	Summary: Plausible non-core ESCRT cell-cycle/centrosome context for CHMP5: mitotic metaphase chromosome alignment. 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. Supporting Evidence: PMID:20616062 depletion of VPS4A, VPS4B, or any of the 11 different human ESCRT-III (CHMP) proteins inhibited abscission PMID:20616062 producing multipolar spindles (most ESCRT-III/VPS4 proteins) or monopolar spindles (CHMP2A or CHMP5) PMID:20616062 ESCRT-III/VPS4 proteins function at centrosomes to help regulate their maintenance or proliferation and then at midbodies during abscission file:human/CHMP5/CHMP5-notes.md Secondary ESCRT contexts should generally be kept as non-core.
GO:0030496 midbody	IDA PMID:26040712 Spastin and ESCRT-III coordinate mitotic spindle disassembly...	KEEP AS NON CORE	Summary: Plausible non-core ESCRT cell-cycle/centrosome context for CHMP5: midbody. 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. Supporting Evidence: PMID:20616062 depletion of VPS4A, VPS4B, or any of the 11 different human ESCRT-III (CHMP) proteins inhibited abscission PMID:20616062 producing multipolar spindles (most ESCRT-III/VPS4 proteins) or monopolar spindles (CHMP2A or CHMP5) PMID:20616062 ESCRT-III/VPS4 proteins function at centrosomes to help regulate their maintenance or proliferation and then at midbodies during abscission file:human/CHMP5/CHMP5-notes.md Secondary ESCRT contexts should generally be kept as non-core.
GO:0031468 nuclear membrane reassembly	IMP PMID:26040713 ESCRT-III controls nuclear envelope reformation.	KEEP AS NON CORE	Summary: Plausible non-core ESCRT nuclear-envelope context for CHMP5: nuclear membrane reassembly. 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. Supporting Evidence: PMID:26040712 ESCRT-III, VPS4 and spastin cooperate to coordinate nuclear envelope sealing and spindle disassembly PMID:26040713 ESCRT-III controls nuclear envelope reformation file:human/CHMP5/CHMP5-notes.md Secondary ESCRT contexts should generally be kept as non-core.
GO:0032585 multivesicular body membrane	IDA PMID:16554368 The ESCRT-III subunit hVps24 is required for degradation but...	ACCEPT	Summary: Supported CHMP5 endosomal/MVB membrane context: multivesicular body membrane. 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. Supporting Evidence: UniProt:Q9NZZ3 involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs PMID:15644320 both LIP5 and CHMP5 function in MVB sorting PMID:15644320 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 file:human/CHMP5/CHMP5-notes.md 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. UniProt:Q9NZZ3 Probable peripherally associated component of the endosomal sorting required for transport complex III (ESCRT-III) PMID:16730941 known components of the human ESCRT III complex PMID:23105106 the ESCRT-III and VPS4 ATPase complexes catalyze the membrane fission events associated with these processes file:human/CHMP5/CHMP5-notes.md 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.
GO:0036258 multivesicular body assembly	NAS PMID:16505166 Recycling of ESCRTs by the AAA-ATPase Vps4 is regulated by a...	ACCEPT	Summary: Supported core CHMP5 MVB/endolysosomal sorting annotation: multivesicular body assembly. 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. Supporting Evidence: UniProt:Q9NZZ3 involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs PMID:15644320 both LIP5 and CHMP5 function in MVB sorting PMID:15644320 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 file:human/CHMP5/CHMP5-notes.md 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. UniProt:Q9NZZ3 enabling degradation of membrane proteins, such as stimulated growth factor receptors PMID:15644320 reduced degradation of the EGFR similar to silencing of LIP5 PMID:17984323 Functional multivesicular bodies are required for autophagic clearance file:human/CHMP5/CHMP5-notes.md Proteostasis-network context: CHMP5 supports endolysosomal degradation through ESCRT/MVB sorting
GO:0039702 viral budding via host ESCRT complex	IDA PMID:24878737 Structure of cellular ESCRT-III spirals and their relationsh...	MARK AS OVER ANNOTATED	Summary: Viral budding is not a core CHMP5 cellular function and is likely over-annotated here: viral budding via host ESCRT complex. 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. Supporting Evidence: PMID:15644320 CHMP5 depletion results in an increase in the release of infectious HIV-1 particles PMID:15644320 both LIP5 and CHMP5 function in MVB sorting, whereas only LIP5 is required for HIV release. file:human/CHMP5/CHMP5-notes.md 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.
GO:0043162 ubiquitin-dependent protein catabolic process via the multivesicular body sorting pathway	IDA PMID:17984323 Functional multivesicular bodies are required for autophagic...	ACCEPT	Summary: Supported core CHMP5 MVB/endolysosomal sorting annotation: ubiquitin-dependent protein catabolic process via the multivesicular body sorting pathway. 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. Supporting Evidence: UniProt:Q9NZZ3 involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs PMID:15644320 both LIP5 and CHMP5 function in MVB sorting PMID:15644320 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 file:human/CHMP5/CHMP5-notes.md 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. UniProt:Q9NZZ3 enabling degradation of membrane proteins, such as stimulated growth factor receptors PMID:15644320 reduced degradation of the EGFR similar to silencing of LIP5 PMID:17984323 Functional multivesicular bodies are required for autophagic clearance file:human/CHMP5/CHMP5-notes.md Proteostasis-network context: CHMP5 supports endolysosomal degradation through ESCRT/MVB sorting
GO:0046761 viral budding from plasma membrane	IDA PMID:24878737 Structure of cellular ESCRT-III spirals and their relationsh...	MARK AS OVER ANNOTATED	Summary: Viral budding is not a core CHMP5 cellular function and is likely over-annotated here: viral budding from plasma membrane. 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. Supporting Evidence: PMID:15644320 CHMP5 depletion results in an increase in the release of infectious HIV-1 particles PMID:15644320 both LIP5 and CHMP5 function in MVB sorting, whereas only LIP5 is required for HIV release. file:human/CHMP5/CHMP5-notes.md 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.
GO:0051469 vesicle fusion with vacuole	NAS PMID:16505166 Recycling of ESCRTs by the AAA-ATPase Vps4 is regulated by a...	MODIFY	Summary: vesicle fusion with vacuole is an over-specific/organellar endpoint for CHMP5 and should be generalized to late endosome-to-lysosome transport. Reason: The evidence supports ESCRT/MVB cargo sorting and downstream degradative trafficking. It does not establish CHMP5 as a direct vesicle-fusion factor. Proposed replacements: late endosome to lysosome transport Supporting Evidence: UniProt:Q9NZZ3 enabling degradation of membrane proteins, such as stimulated growth factor receptors PMID:15644320 reduced degradation of the EGFR similar to silencing of LIP5 PMID:17984323 Functional multivesicular bodies are required for autophagic clearance file:human/CHMP5/CHMP5-notes.md Proteostasis-network context: CHMP5 supports endolysosomal degradation through ESCRT/MVB sorting
GO:0061763 multivesicular body-lysosome fusion	NAS PMID:16505166 Recycling of ESCRTs by the AAA-ATPase Vps4 is regulated by a...	MODIFY	Summary: multivesicular body-lysosome fusion is an over-specific/organellar endpoint for CHMP5 and should be generalized to late endosome-to-lysosome transport. Reason: The evidence supports ESCRT/MVB cargo sorting and downstream degradative trafficking. It does not establish CHMP5 as a direct vesicle-fusion factor. Proposed replacements: late endosome to lysosome transport Supporting Evidence: UniProt:Q9NZZ3 enabling degradation of membrane proteins, such as stimulated growth factor receptors PMID:15644320 reduced degradation of the EGFR similar to silencing of LIP5 PMID:17984323 Functional multivesicular bodies are required for autophagic clearance file:human/CHMP5/CHMP5-notes.md Proteostasis-network context: CHMP5 supports endolysosomal degradation through ESCRT/MVB sorting
GO:0061952 midbody abscission	IMP PMID:20616062 Human ESCRT-III and VPS4 proteins are required for centrosom...	KEEP AS NON CORE	Summary: Plausible non-core ESCRT cell-cycle/centrosome context for CHMP5: midbody abscission. 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. Supporting Evidence: PMID:20616062 depletion of VPS4A, VPS4B, or any of the 11 different human ESCRT-III (CHMP) proteins inhibited abscission PMID:20616062 producing multipolar spindles (most ESCRT-III/VPS4 proteins) or monopolar spindles (CHMP2A or CHMP5) PMID:20616062 ESCRT-III/VPS4 proteins function at centrosomes to help regulate their maintenance or proliferation and then at midbodies during abscission file:human/CHMP5/CHMP5-notes.md Secondary ESCRT contexts should generally be kept as non-core.
GO:0071985 multivesicular body sorting pathway	IDA PMID:16554368 The ESCRT-III subunit hVps24 is required for degradation but...	ACCEPT	Summary: Supported core CHMP5 MVB/endolysosomal sorting annotation: multivesicular body sorting pathway. 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. Supporting Evidence: UniProt:Q9NZZ3 involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs PMID:15644320 both LIP5 and CHMP5 function in MVB sorting PMID:15644320 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 file:human/CHMP5/CHMP5-notes.md 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. UniProt:Q9NZZ3 enabling degradation of membrane proteins, such as stimulated growth factor receptors PMID:15644320 reduced degradation of the EGFR similar to silencing of LIP5 PMID:17984323 Functional multivesicular bodies are required for autophagic clearance file:human/CHMP5/CHMP5-notes.md Proteostasis-network context: CHMP5 supports endolysosomal degradation through ESCRT/MVB sorting
GO:0090148 membrane fission	NAS PMID:19234443 Membrane scission by the ESCRT-III complex.	ACCEPT	Summary: Supported ESCRT-pathway membrane-fission output for CHMP5. 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. Supporting Evidence: UniProt:Q9NZZ3 Probable peripherally associated component of the endosomal sorting required for transport complex III (ESCRT-III) PMID:16730941 known components of the human ESCRT III complex PMID:23105106 the ESCRT-III and VPS4 ATPase complexes catalyze the membrane fission events associated with these processes file:human/CHMP5/CHMP5-notes.md 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. PMID:18385515 LIP5 binds preferentially to soluble CHMP5 PMID:18385515 These studies point to a role for direct binding between LIP5 and ESCRT-III proteins PMID:23105106 promoting assembly of active VPS4 enzymes on the polymeric ESCRT-III substrate PMID:23105106 formation of stable VPS4 complexes with both LIP5 and CHMP5 requires LIP5 to bind both a MIM1-containing ESCRT-III protein and CHMP5 file:human/CHMP5/CHMP5-notes.md 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.
GO:0097352 autophagosome maturation	IMP PMID:17984323 Functional multivesicular bodies are required for autophagic...	KEEP AS NON CORE	Summary: Plausible PN-relevant but non-core CHMP5 autophagy/endolysosomal context: autophagosome maturation. 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. Supporting Evidence: PMID:17984323 Functional multivesicular bodies are required for autophagic clearance PMID:17984323 functional MVBs are required to prevent accumulation of abnormal proteins PMID:30061757 CHMP5-one of the IcsB targets and a component of the ESCRT-III complex-specifically affected S. flexneri escape from host autophagy. file:human/CHMP5/CHMP5-notes.md the cached CHMP5 GOA autophagy annotations mostly derive from ESCRT-complex context rather than CHMP5-specific autophagosome sealing assays
GO:1901673 regulation of mitotic spindle assembly	IMP PMID:20616062 Human ESCRT-III and VPS4 proteins are required for centrosom...	KEEP AS NON CORE	Summary: Plausible non-core ESCRT cell-cycle/centrosome context for CHMP5: regulation of mitotic spindle assembly. 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. Supporting Evidence: PMID:20616062 depletion of VPS4A, VPS4B, or any of the 11 different human ESCRT-III (CHMP) proteins inhibited abscission PMID:20616062 producing multipolar spindles (most ESCRT-III/VPS4 proteins) or monopolar spindles (CHMP2A or CHMP5) PMID:20616062 ESCRT-III/VPS4 proteins function at centrosomes to help regulate their maintenance or proliferation and then at midbodies during abscission file:human/CHMP5/CHMP5-notes.md Secondary ESCRT contexts should generally be kept as non-core.
GO:1902774 late endosome to lysosome transport	IMP PMID:17984323 Functional multivesicular bodies are required for autophagic...	ACCEPT	Summary: Supported CHMP5 endolysosomal degradation route annotation. 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. Supporting Evidence: UniProt:Q9NZZ3 involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs PMID:15644320 both LIP5 and CHMP5 function in MVB sorting PMID:15644320 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 file:human/CHMP5/CHMP5-notes.md 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. UniProt:Q9NZZ3 enabling degradation of membrane proteins, such as stimulated growth factor receptors PMID:15644320 reduced degradation of the EGFR similar to silencing of LIP5 PMID:17984323 Functional multivesicular bodies are required for autophagic clearance file:human/CHMP5/CHMP5-notes.md Proteostasis-network context: CHMP5 supports endolysosomal degradation through ESCRT/MVB sorting
GO:1904930 amphisome membrane	IDA PMID:17984323 Functional multivesicular bodies are required for autophagic...	KEEP AS NON CORE	Summary: Plausible PN-relevant but non-core CHMP5 autophagy/endolysosomal context: amphisome membrane. 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. Supporting Evidence: PMID:17984323 Functional multivesicular bodies are required for autophagic clearance PMID:17984323 functional MVBs are required to prevent accumulation of abnormal proteins PMID:30061757 CHMP5-one of the IcsB targets and a component of the ESCRT-III complex-specifically affected S. flexneri escape from host autophagy. file:human/CHMP5/CHMP5-notes.md the cached CHMP5 GOA autophagy annotations mostly derive from ESCRT-complex context rather than CHMP5-specific autophagosome sealing assays
GO:0030496 midbody	EXP PMID:17853893 Human ESCRT and ALIX proteins interact with proteins of the ...	KEEP AS NON CORE	Summary: Plausible non-core ESCRT cell-cycle/centrosome context for CHMP5: midbody. 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. Supporting Evidence: PMID:20616062 depletion of VPS4A, VPS4B, or any of the 11 different human ESCRT-III (CHMP) proteins inhibited abscission PMID:20616062 producing multipolar spindles (most ESCRT-III/VPS4 proteins) or monopolar spindles (CHMP2A or CHMP5) PMID:20616062 ESCRT-III/VPS4 proteins function at centrosomes to help regulate their maintenance or proliferation and then at midbodies during abscission file:human/CHMP5/CHMP5-notes.md Secondary ESCRT contexts should generally be kept as non-core.
GO:0071222 cellular response to lipopolysaccharide	IMP PMID:27812135 Characterization and Genetic Analyses of New Genes Coding fo...	MARK AS OVER ANNOTATED	Summary: cellular response to lipopolysaccharide is not established as a CHMP5 core response function. 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. Supporting Evidence: PMID:27812135 CHMP5ESCRTIII proteins are required for late MVB formation and their fusion with the lysosome file:human/CHMP5/CHMP5-notes.md The NOD2/LPS/MDP annotations are not core CHMP5 function. file:human/CHMP5/CHMP5-notes.md the study itself says these new interacting proteins did not appear to be major NOD2-dependent NF-kappaB regulators in the assay
GO:0071225 cellular response to muramyl dipeptide	IMP PMID:27812135 Characterization and Genetic Analyses of New Genes Coding fo...	MARK AS OVER ANNOTATED	Summary: cellular response to muramyl dipeptide is not established as a CHMP5 core response function. 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. Supporting Evidence: PMID:27812135 CHMP5ESCRTIII proteins are required for late MVB formation and their fusion with the lysosome file:human/CHMP5/CHMP5-notes.md The NOD2/LPS/MDP annotations are not core CHMP5 function. file:human/CHMP5/CHMP5-notes.md the study itself says these new interacting proteins did not appear to be major NOD2-dependent NF-kappaB regulators in the assay
GO:0045296 cadherin binding	HDA PMID:25468996 E-cadherin interactome complexity and robustness resolved by...	MARK AS OVER ANNOTATED	Summary: Cadherin binding from high-throughput proteomics is not informative for CHMP5 function. Reason: The cadherin-binding annotation is from broad affinity proteomics and does not connect to the supported ESCRT/MVB/LIP5-VPS4 role of CHMP5. Supporting Evidence: PMID:25468996 E-cadherin interactome complexity and robustness resolved by quantitative proteomics file:human/CHMP5/CHMP5-notes.md 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.
GO:0036258 multivesicular body assembly	NAS PMID:20588296 Membrane budding and scission by the ESCRT machinery: it's a...	ACCEPT	Summary: Supported core CHMP5 MVB/endolysosomal sorting annotation: multivesicular body assembly. 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. Supporting Evidence: UniProt:Q9NZZ3 involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs PMID:15644320 both LIP5 and CHMP5 function in MVB sorting PMID:15644320 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 file:human/CHMP5/CHMP5-notes.md 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. UniProt:Q9NZZ3 enabling degradation of membrane proteins, such as stimulated growth factor receptors PMID:15644320 reduced degradation of the EGFR similar to silencing of LIP5 PMID:17984323 Functional multivesicular bodies are required for autophagic clearance file:human/CHMP5/CHMP5-notes.md Proteostasis-network context: CHMP5 supports endolysosomal degradation through ESCRT/MVB sorting
GO:1904903 ESCRT III complex disassembly	NAS PMID:20588296 Membrane budding and scission by the ESCRT machinery: it's a...	ACCEPT	Summary: Supported core CHMP5 role in ESCRT-III complex disassembly/recycling. 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. Supporting Evidence: PMID:18385515 LIP5 binds preferentially to soluble CHMP5 PMID:18385515 These studies point to a role for direct binding between LIP5 and ESCRT-III proteins PMID:23105106 promoting assembly of active VPS4 enzymes on the polymeric ESCRT-III substrate PMID:23105106 formation of stable VPS4 complexes with both LIP5 and CHMP5 requires LIP5 to bind both a MIM1-containing ESCRT-III protein and CHMP5 file:human/CHMP5/CHMP5-notes.md 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. UniProt:Q9NZZ3 Probable peripherally associated component of the endosomal sorting required for transport complex III (ESCRT-III) PMID:16730941 known components of the human ESCRT III complex PMID:23105106 the ESCRT-III and VPS4 ATPase complexes catalyze the membrane fission events associated with these processes file:human/CHMP5/CHMP5-notes.md 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.
GO:0005515 protein binding	IPI PMID:18385515 Novel interactions of ESCRT-III with LIP5 and VPS4 and their...	MARK AS OVER ANNOTATED	Summary: Generic protein binding does not capture the specific CHMP5/LIP5/VPS4-ESCRT regulatory mechanism. 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. Supporting Evidence: PMID:15644320 We identify CHMP5 as a LIP5-binding protein and show that CHMP5 is primarily cytosolic. PMID:18385515 LIP5 binds preferentially to soluble CHMP5 PMID:23105106 the second LIP5 MIT module binds with unusually high affinity to a novel MIM element within the ESCRT-III protein CHMP5 file:human/CHMP5/CHMP5-notes.md 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.
GO:0005515 protein binding	IPI PMID:23105106 Interactions of the human LIP5 regulatory protein with endos...	MARK AS OVER ANNOTATED	Summary: Generic protein binding does not capture the specific CHMP5/LIP5/VPS4-ESCRT regulatory mechanism. 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. Supporting Evidence: PMID:15644320 We identify CHMP5 as a LIP5-binding protein and show that CHMP5 is primarily cytosolic. PMID:18385515 LIP5 binds preferentially to soluble CHMP5 PMID:23105106 the second LIP5 MIT module binds with unusually high affinity to a novel MIM element within the ESCRT-III protein CHMP5 file:human/CHMP5/CHMP5-notes.md 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.
GO:0005515 protein binding	IPI PMID:15644320 The role of LIP5 and CHMP5 in multivesicular body formation ...	MARK AS OVER ANNOTATED	Summary: Generic protein binding does not capture the specific CHMP5/LIP5/VPS4-ESCRT regulatory mechanism. 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. Supporting Evidence: PMID:15644320 We identify CHMP5 as a LIP5-binding protein and show that CHMP5 is primarily cytosolic. PMID:18385515 LIP5 binds preferentially to soluble CHMP5 PMID:23105106 the second LIP5 MIT module binds with unusually high affinity to a novel MIM element within the ESCRT-III protein CHMP5 file:human/CHMP5/CHMP5-notes.md 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.
GO:0005829 cytosol	IDA PMID:15644320 The role of LIP5 and CHMP5 in multivesicular body formation ...	KEEP AS NON CORE	Summary: True or plausible broad CHMP5 location: cytosol. Reason: CHMP5 is primarily cytosolic and can be detected in broad compartments, but broad locations do not define the core function. Supporting Evidence: UniProt:Q9NZZ3 Cytoplasm, cytosol PMID:15644320 We identify CHMP5 as a LIP5-binding protein and show that CHMP5 is primarily cytosolic. file:human/CHMP5/CHMP5-notes.md Non-core: cytosol/nucleus/exosome locations, midbody/cytokinesis, spindle/centrosome, nuclear envelope/pore reassembly, plasma membrane repair, infection/autophagy contexts, and viral budding.
GO:0046755 viral budding	IMP PMID:15644320 The role of LIP5 and CHMP5 in multivesicular body formation ...	MARK AS OVER ANNOTATED	Summary: Viral budding is not a core CHMP5 cellular function and is likely over-annotated here: viral budding. 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. Supporting Evidence: PMID:15644320 CHMP5 depletion results in an increase in the release of infectious HIV-1 particles PMID:15644320 both LIP5 and CHMP5 function in MVB sorting, whereas only LIP5 is required for HIV release. file:human/CHMP5/CHMP5-notes.md 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.
GO:0071985 multivesicular body sorting pathway	IMP PMID:15644320 The role of LIP5 and CHMP5 in multivesicular body formation ...	ACCEPT	Summary: Supported core CHMP5 MVB/endolysosomal sorting annotation: multivesicular body sorting pathway. 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. Supporting Evidence: UniProt:Q9NZZ3 involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs PMID:15644320 both LIP5 and CHMP5 function in MVB sorting PMID:15644320 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 file:human/CHMP5/CHMP5-notes.md 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. UniProt:Q9NZZ3 enabling degradation of membrane proteins, such as stimulated growth factor receptors PMID:15644320 reduced degradation of the EGFR similar to silencing of LIP5 PMID:17984323 Functional multivesicular bodies are required for autophagic clearance file:human/CHMP5/CHMP5-notes.md Proteostasis-network context: CHMP5 supports endolysosomal degradation through ESCRT/MVB sorting
GO:0010824 regulation of centrosome duplication	IMP PMID:20616062 Human ESCRT-III and VPS4 proteins are required for centrosom...	KEEP AS NON CORE	Summary: Plausible non-core ESCRT cell-cycle/centrosome context for CHMP5: regulation of centrosome duplication. 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. Supporting Evidence: PMID:20616062 depletion of VPS4A, VPS4B, or any of the 11 different human ESCRT-III (CHMP) proteins inhibited abscission PMID:20616062 producing multipolar spindles (most ESCRT-III/VPS4 proteins) or monopolar spindles (CHMP2A or CHMP5) PMID:20616062 ESCRT-III/VPS4 proteins function at centrosomes to help regulate their maintenance or proliferation and then at midbodies during abscission file:human/CHMP5/CHMP5-notes.md Secondary ESCRT contexts should generally be kept as non-core.
GO:0070062 extracellular exosome	HDA PMID:23533145 In-depth proteomic analyses of exosomes isolated from expres...	KEEP AS NON CORE	Summary: Extracellular exosome detection is retained as broad non-core location context. Reason: High-throughput exosome proteomics can be compatible with ESCRT/exosome biology, but it does not establish the CHMP5 core cellular function. Supporting Evidence: PMID:23533145 In-depth proteomic analyses of exosomes isolated from expressed prostatic secretions in urine PMID:19056867 Large-scale proteomics and phosphoproteomics of urinary exosomes PMID:20458337 MHC class II-associated proteins in B-cell exosomes and potential functional implications for exosome biogenesis file:human/CHMP5/CHMP5-notes.md Non-core: cytosol/nucleus/exosome locations, midbody/cytokinesis, spindle/centrosome, nuclear envelope/pore reassembly, plasma membrane repair, infection/autophagy contexts, and viral budding.
GO:0070062 extracellular exosome	HDA PMID:19056867 Large-scale proteomics and phosphoproteomics of urinary exos...	KEEP AS NON CORE	Summary: Extracellular exosome detection is retained as broad non-core location context. Reason: High-throughput exosome proteomics can be compatible with ESCRT/exosome biology, but it does not establish the CHMP5 core cellular function. Supporting Evidence: PMID:23533145 In-depth proteomic analyses of exosomes isolated from expressed prostatic secretions in urine PMID:19056867 Large-scale proteomics and phosphoproteomics of urinary exosomes PMID:20458337 MHC class II-associated proteins in B-cell exosomes and potential functional implications for exosome biogenesis file:human/CHMP5/CHMP5-notes.md Non-core: cytosol/nucleus/exosome locations, midbody/cytokinesis, spindle/centrosome, nuclear envelope/pore reassembly, plasma membrane repair, infection/autophagy contexts, and viral budding.
GO:0070062 extracellular exosome	HDA PMID:20458337 MHC class II-associated proteins in B-cell exosomes and pote...	KEEP AS NON CORE	Summary: Extracellular exosome detection is retained as broad non-core location context. Reason: High-throughput exosome proteomics can be compatible with ESCRT/exosome biology, but it does not establish the CHMP5 core cellular function. Supporting Evidence: PMID:23533145 In-depth proteomic analyses of exosomes isolated from expressed prostatic secretions in urine PMID:19056867 Large-scale proteomics and phosphoproteomics of urinary exosomes PMID:20458337 MHC class II-associated proteins in B-cell exosomes and potential functional implications for exosome biogenesis file:human/CHMP5/CHMP5-notes.md Non-core: cytosol/nucleus/exosome locations, midbody/cytokinesis, spindle/centrosome, nuclear envelope/pore reassembly, plasma membrane repair, infection/autophagy contexts, and viral budding.
GO:0005515 protein binding	IPI PMID:21543490 Mechanism of inhibition of retrovirus release from cells by ...	MARK AS OVER ANNOTATED	Summary: Generic protein binding does not capture the specific CHMP5/LIP5/VPS4-ESCRT regulatory mechanism. 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. Supporting Evidence: PMID:15644320 We identify CHMP5 as a LIP5-binding protein and show that CHMP5 is primarily cytosolic. PMID:18385515 LIP5 binds preferentially to soluble CHMP5 PMID:23105106 the second LIP5 MIT module binds with unusually high affinity to a novel MIM element within the ESCRT-III protein CHMP5 file:human/CHMP5/CHMP5-notes.md 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.
GO:0005829 cytosol	TAS Reactome:R-HSA-3159232	KEEP AS NON CORE	Summary: True or plausible broad CHMP5 location: cytosol. Reason: CHMP5 is primarily cytosolic and can be detected in broad compartments, but broad locations do not define the core function. Supporting Evidence: UniProt:Q9NZZ3 Cytoplasm, cytosol PMID:15644320 We identify CHMP5 as a LIP5-binding protein and show that CHMP5 is primarily cytosolic. file:human/CHMP5/CHMP5-notes.md Non-core: cytosol/nucleus/exosome locations, midbody/cytokinesis, spindle/centrosome, nuclear envelope/pore reassembly, plasma membrane repair, infection/autophagy contexts, and viral budding.
GO:0005829 cytosol	TAS Reactome:R-HSA-917693	KEEP AS NON CORE	Summary: True or plausible broad CHMP5 location: cytosol. Reason: CHMP5 is primarily cytosolic and can be detected in broad compartments, but broad locations do not define the core function. Supporting Evidence: UniProt:Q9NZZ3 Cytoplasm, cytosol PMID:15644320 We identify CHMP5 as a LIP5-binding protein and show that CHMP5 is primarily cytosolic. file:human/CHMP5/CHMP5-notes.md Non-core: cytosol/nucleus/exosome locations, midbody/cytokinesis, spindle/centrosome, nuclear envelope/pore reassembly, plasma membrane repair, infection/autophagy contexts, and viral budding.

📄 View Raw YAML

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.

Gene Description

Existing Annotations Review

Core Functions

References

Suggested Questions for Experts

Suggested Experiments

📚 Additional Documentation

Notes

CHMP5 notes

Working synthesis

Curation decisions

Deep research status

Description cleanup note

Pn Notes

CHMP5 PN Consistency Notes

Source Files Checked

Deep Research Files

AIGR Review Snapshot

PN Consistency Summary

Full Consistency Review

PN Dossier Context

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

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

Projected GO annotations (3)

Note

📄 View Raw YAML