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.
| 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. |
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Download this section (compressed HTML)Q: Can endogenous CHMP5 depletion/rescue separate its direct LIP5/VTA1-VPS4 regulatory role from pathway-level ESCRT-III membrane-fission annotations?
Q: Which CHMP5-specific autophagy annotations are supported by direct autophagosome closure or maturation assays rather than by ESCRT complex membership?
Q: 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?
Experiment: 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.
Experiment: 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.
Experiment: 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.
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