CHMP3 (also known as VPS24/hVps24) is a core component of the ESCRT-III complex, belonging to the SNF7 protein family. It functions as a non-enzymatic structural subunit that co-polymerizes with CHMP2A and CHMP4B to form helical/spiral polymers that constrict and sever membrane necks in "reverse topology" membrane fission events (budding away from the cytosol). CHMP3 is maintained in an autoinhibited cytosolic state and is activated upon recruitment to membranes through interaction with other ESCRT-III components. The VPS4 AAA+ ATPase disassembles CHMP3-containing polymers after membrane scission. CHMP3 participates in multivesicular body (MVB) formation and cargo sorting to lysosomes, cytokinetic abscission at the midbody, nuclear envelope reformation during telophase, plasma membrane repair, and is hijacked by enveloped viruses (notably HIV-1) for budding. It also plays roles in autophagosome maturation and endosomal proteostasis relevant to neurodegenerative disease.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0005771 multivesicular body | IBA GO_REF:0000033 | ACCEPT | Summary: CHMP3/VPS24 is a core ESCRT-III subunit that functions at MVBs to mediate ILV formation. IBA annotation is phylogenetically sound as Vps24 function at MVBs is conserved from yeast. Reason: CHMP3 localization to MVBs is well-supported. Bache et al. (PMID:16554368) showed endogenous hVps24 localized mainly to late endosomes and MVBs. The deep research confirms CHMP3 acts at endosomal limiting membranes for ILV formation. Supporting Evidence: PMID:16554368 Like Tsg101, endogenous hVps24 localized mainly to late endosomes. file:human/CHMP3/CHMP3-deep-research-falcon.md model: Edison Scientific Literature |
| GO:0015031 protein transport | IBA GO_REF:0000033 | ACCEPT | Summary: CHMP3 participates in protein transport as part of ESCRT-III mediated cargo sorting to lysosomes. Reason: While general, this term is appropriate as CHMP3 is required for transport of cargo proteins like EGFR from endosomes to lysosomes (PMID:16554368). Supporting Evidence: PMID:16554368 Depletion of hVps24 by siRNA showed that this ESCRT subunit, like Tsg101, is important for degradation of the epidermal growth factor (EGF) receptor (EGFR) and for transport of the receptor from early endosomes to lysosomes. |
| GO:0032509 endosome transport via multivesicular body sorting pathway | IBA GO_REF:0000033 | ACCEPT | Summary: CHMP3 is essential for MVB-mediated endosomal transport as a core ESCRT-III component. Reason: This is a core function of CHMP3. The MVB sorting pathway requires ESCRT-III for ILV formation and cargo sorting. Supporting Evidence: PMID:16554368 hVps24 is required for degradation but not silencing of the epidermal growth factor receptor |
| GO:0045324 late endosome to vacuole transport | IBA GO_REF:0000033 | ACCEPT | Summary: CHMP3 is required for late endosome to lysosome transport (vacuole is the yeast equivalent of lysosome). Reason: Conserved function from yeast Vps24. In human cells, CHMP3 is required for transport from late endosomes to lysosomes. Supporting Evidence: PMID:16554368 Electron microscopy of hVps24-depleted cells showed an accumulation of EGFRs in MVEs that were significantly smaller than those in control cells, probably because of an impaired fusion with lyso-bisphosphatidic acid-positive late endosomes/lysosomes. |
| GO:0000815 ESCRT III complex | IBA GO_REF:0000033 | ACCEPT | Summary: CHMP3 is a core structural subunit of the ESCRT-III complex. This is one of the most fundamental aspects of CHMP3 function. Reason: CHMP3/VPS24 is unambiguously a core ESCRT-III component, demonstrated by structural studies showing CHMP2A-CHMP3 helical copolymers (PMID:18687924) and functional studies. Supporting Evidence: PMID:18687924 CHMP2A and CHMP3 copolymerized in solution, and their membrane targeting was cooperatively enhanced on planar lipid bilayers. |
| GO:0000776 kinetochore | IEA GO_REF:0000117 | ACCEPT | Summary: IEA annotation suggesting CHMP3 localizes to kinetochores. This is supported by a global screen (PMID reference in later IDA annotation). Reason: CHMP3 was reported to localize to kinetochores in a global screen for proteins with mitotic functions (cited in PMID:20616062). While not a primary localization, it appears to be a real secondary site. Supporting Evidence: PMID:20616062 CHMP3 and CHMP4, were recently reported to localize to kinetochores in a global screen for proteins with possible mitotic functions |
| GO:0001778 plasma membrane repair | IEA GO_REF:0000117 | ACCEPT | Summary: ESCRT machinery including CHMP3 is required for plasma membrane repair. Reason: Supported by direct evidence (PMID:24482116) showing ESCRT machinery is required for plasma membrane repair. The IEA correctly captures this established ESCRT-III function. Supporting Evidence: PMID:24482116 ESCRT machinery is required for plasma membrane repair |
| GO:0005643 nuclear pore | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: IEA suggesting CHMP3 localizes to nuclear pores. While ESCRT-III acts at the nuclear envelope during reformation, nuclear pore localization specifically is less well established for CHMP3. Reason: ESCRT-III (particularly CHMP2A) localizes to nucleo-cytoplasmic channels during NE reformation (PMID:26040713), which are distinct from nuclear pores. However, proximity to NE fenestrations may be captured by this term. Not a core localization. Supporting Evidence: PMID:26040713 On these sheets, CHMP2A localised to discrete regions, with intact NE being devoid of label, but with CHMP2A preferentially...decorating nucleo-cytoplasmic channels |
| GO:0005765 lysosomal membrane | IEA GO_REF:0000117 | ACCEPT | Summary: CHMP3 may transiently associate with lysosomal membranes during ESCRT-dependent processes. Reason: ESCRT-III is implicated in lysosomal microautophagy and MVB-lysosome fusion processes. Experimental evidence (IDA, PMID:17984323) supports lysosomal membrane localization. Supporting Evidence: PMID:17984323 Functional multivesicular bodies are required for autophagic clearance |
| GO:0005768 endosome | IEA GO_REF:0000044 | ACCEPT | Summary: CHMP3 localizes to endosomes as part of ESCRT-III function in MVB biogenesis. Reason: Well-established localization. CHMP3/hVps24 localizes mainly to late endosomes and functions in endosomal sorting (PMID:16554368). Supporting Evidence: PMID:16554368 Like Tsg101, endogenous hVps24 localized mainly to late endosomes. |
| GO:0005828 kinetochore microtubule | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: IEA annotation for kinetochore microtubule localization of CHMP3. Reason: While CHMP3 has been found at kinetochores in screens (PMID:20616062), kinetochore microtubule localization specifically is less directly supported. This is secondary to core ESCRT-III functions. Supporting Evidence: PMID:20616062 CHMP3 and CHMP4, were recently reported to localize to kinetochores in a global screen |
| GO:0005829 cytosol | IEA GO_REF:0000044 | ACCEPT | Summary: CHMP3 exists in an autoinhibited form in the cytosol before membrane recruitment. Reason: ESCRT-III subunits including CHMP3 are cytosolic in their autoinhibited form and are recruited to membranes upon activation. This is well established from structural and biochemical studies. Supporting Evidence: PMID:18395747 Structural basis for autoinhibition of ESCRT-III CHMP3 |
| GO:0006915 apoptotic process | IEA GO_REF:0000043 | KEEP AS NON CORE | Summary: IEA annotation linking CHMP3 to apoptosis. Isoform 2 of CHMP3 can prevent stress-mediated cell death in yeast. Reason: UniProt notes that Isoform 2 prevents stress-mediated cell death in yeast. This is a secondary function not representing core ESCRT-III activity. May reflect indirect effects of ESCRT dysfunction. |
| GO:0007034 vacuolar transport | IEA GO_REF:0000002 | ACCEPT | Summary: CHMP3/VPS24 functions in vacuolar transport (vacuole being the yeast equivalent of lysosome). Reason: This reflects the conserved function of Vps24 in vacuolar protein sorting. InterPro domain mapping correctly identifies this core function. |
| GO:0015031 protein transport | IEA GO_REF:0000043 | ACCEPT | Summary: Duplicate of IBA annotation. CHMP3 functions in protein transport via ESCRT-III. Reason: Same as IBA annotation - CHMP3 is required for protein transport to lysosomes as part of ESCRT-III function. |
| GO:0016020 membrane | IEA GO_REF:0000044 | ACCEPT | Summary: CHMP3 associates with membranes during ESCRT-III function. Reason: While very general, this is accurate. CHMP3 is recruited to membranes where it polymerizes to effect membrane scission. |
| GO:0031902 late endosome membrane | IEA GO_REF:0000044 | ACCEPT | Summary: CHMP3 localizes to late endosome membranes as part of ESCRT-III function. Reason: Well-supported. Bache et al. showed endogenous hVps24 localized mainly to late endosomes (PMID:16554368). Supporting Evidence: PMID:16554368 Like Tsg101, endogenous hVps24 localized mainly to late endosomes. |
| GO:0032585 multivesicular body membrane | IEA GO_REF:0000117 | ACCEPT | Summary: CHMP3 localizes to MVB membranes where it functions in ILV formation. Reason: Core localization for ESCRT-III function in MVB biogenesis. Supported by direct evidence (PMID:16554368). Supporting Evidence: PMID:16554368 Electron microscopy of hVps24-depleted cells showed an accumulation of EGFRs in MVEs |
| GO:0039702 viral budding via host ESCRT complex | IEA GO_REF:0000117 | ACCEPT | Summary: CHMP3 is part of the ESCRT machinery hijacked by enveloped viruses for budding. Reason: Well-established core function. CHMP3 is part of the minimal ESCRT-III set for HIV-1 budding (PMID:14505570, PMID:16740483). Supporting Evidence: PMID:14505570 dominant-negative mutants of late-acting human class E proteins arrested HIV-1 budding |
| GO:0043162 ubiquitin-dependent protein catabolic process via the multivesicular body sorting pathway | IEA GO_REF:0000117 | ACCEPT | Summary: CHMP3 functions in ubiquitin-dependent cargo sorting to MVBs. Reason: Core ESCRT-III function. Ubiquitinated cargo like EGFR and alpha-synuclein require ESCRT-III including CHMP3 for lysosomal degradation. Supporting Evidence: PMID:16554368 ESCRT-I, -II, and -III, are thought to mediate the biogenesis of multivesicular endosomes (MVEs) and endosomal sorting of ubiquitinated membrane proteins |
| GO:0046761 viral budding from plasma membrane | IEA GO_REF:0000117 | ACCEPT | Summary: CHMP3 functions in viral budding from plasma membrane as part of ESCRT-III. Reason: HIV-1 buds from the plasma membrane using ESCRT machinery. CHMP3 is part of the minimal scission set for HIV-1 budding. Supporting Evidence: PMID:16740483 Structural basis for budding by the ESCRT-III factor CHMP3 |
| GO:0051301 cell division | IEA GO_REF:0000043 | ACCEPT | Summary: CHMP3 functions in cell division via its role in cytokinetic abscission and centrosome maintenance. Reason: ESCRT-III is required for cytokinetic abscission. Depletion of any CHMP protein inhibits abscission (PMID:20616062). Supporting Evidence: PMID:20616062 depletion of VPS4A, VPS4B, or any of the 11 different human ESCRT-III (CHMP) proteins inhibited abscission |
| GO:0061952 midbody abscission | IEA GO_REF:0000117 | ACCEPT | Summary: CHMP3 is required for midbody abscission during cytokinesis. Reason: Core ESCRT-III function. Systematic analysis showed CHMP3 depletion inhibits abscission (PMID:20616062). Supporting Evidence: PMID:20616062 depletion of VPS4A, VPS4B, or any of the 11 different human ESCRT-III (CHMP) proteins inhibited abscission |
| GO:0071985 multivesicular body sorting pathway | IEA GO_REF:0000117 | ACCEPT | Summary: CHMP3 functions in the MVB sorting pathway as a core ESCRT-III component. Reason: Core function. CHMP3/hVps24 is required for MVB-mediated receptor degradation (PMID:16554368). Supporting Evidence: PMID:16554368 The ESCRT-III subunit hVps24 is required for degradation but not silencing of the epidermal growth factor receptor |
| GO:0097352 autophagosome maturation | IEA GO_REF:0000117 | ACCEPT | Summary: ESCRT-III including CHMP3 is required for autophagosome maturation. Reason: Supported by experimental evidence showing functional MVBs are required for autophagic clearance (PMID:17984323). Supporting Evidence: PMID:17984323 Functional multivesicular bodies are required for autophagic clearance of protein aggregates |
| GO:1902774 late endosome to lysosome transport | IEA GO_REF:0000117 | ACCEPT | Summary: CHMP3 is required for late endosome to lysosome transport. Reason: CHMP3 depletion impairs MVB-lysosome fusion and EGFR degradation (PMID:16554368). Supporting Evidence: PMID:16554368 hVps24 depletion results in the accumulation of EGFRs in small endosomes... probably because of an impaired fusion with lyso-bisphosphatidic acid-positive late endosomes/lysosomes |
| GO:1904930 amphisome membrane | IEA GO_REF:0000117 | ACCEPT | Summary: CHMP3 localizes to amphisome membranes during autophagy. Reason: Amphisomes are intermediates in autophagy formed by fusion of autophagosomes with endosomes. ESCRT-III function is required for autophagy (PMID:17984323). |
| GO:0005546 phosphatidylinositol-4,5-bisphosphate binding | IEA GO_REF:0000107 | MODIFY | Summary: IEA annotation for PI(4,5)P2 binding by CHMP3. Reason: UniProt indicates CHMP3 selectively binds PI(3,5)P2 and PI(3,4)P2 in preference to other phosphoinositides. PI(4,5)P2 binding is less specific. The annotation should be more accurate to the tested lipid preferences. Proposed replacements: phosphatidylinositol-3,5-bisphosphate binding |
| GO:0005769 early endosome | IEA GO_REF:0000107 | ACCEPT | Summary: CHMP3 can be found on early endosomes, though predominantly on late endosomes. Reason: Bache et al. note that while bulk hVps24 is on late endosomes, some EEA1-positive early endosomes do contain hVps24 (PMID:16554368). Supporting Evidence: PMID:16554368 we did observe a few EEA1-positive structures that labeled for endogenous hVps24 |
| GO:0005770 late endosome | IEA GO_REF:0000107 | ACCEPT | Summary: CHMP3 localizes predominantly to late endosomes. Reason: Primary localization site for CHMP3/hVps24 (PMID:16554368). Supporting Evidence: PMID:16554368 Like Tsg101, endogenous hVps24 localized mainly to late endosomes. |
| GO:0008333 endosome to lysosome transport | IEA GO_REF:0000107 | ACCEPT | Summary: CHMP3 is required for endosome to lysosome transport. Reason: Core function of CHMP3/hVps24 in ESCRT-III-mediated cargo trafficking (PMID:16554368). Supporting Evidence: PMID:16554368 Depletion of hVps24 by siRNA showed that this ESCRT subunit, like Tsg101, is important for degradation of the epidermal growth factor (EGF) receptor (EGFR) and for transport of the receptor from early endosomes to lysosomes |
| GO:0030496 midbody | IEA GO_REF:0000120 | ACCEPT | Summary: CHMP3 localizes to the midbody during cytokinesis. Reason: ESCRT-III proteins localize to the midbody for abscission. Supported by direct evidence (PMID:20616062, PMID:26040712). Supporting Evidence: PMID:20616062 VPS4 proteins concentrated at spindle poles during mitosis and then at midbodies during cytokinesis |
| GO:0032467 positive regulation of cytokinesis | IEA GO_REF:0000107 | ACCEPT | Summary: CHMP3 positively regulates cytokinesis through its role in abscission. Reason: ESCRT-III is required for cytokinesis. Depletion inhibits abscission (PMID:20616062). Supporting Evidence: PMID:20616062 depletion of VPS4A, VPS4B, or any of the 11 different human ESCRT-III (CHMP) proteins inhibited abscission |
| GO:0051036 regulation of endosome size | IEA GO_REF:0000107 | ACCEPT | Summary: CHMP3 depletion affects endosome size. Reason: hVps24 depletion causes accumulation of EGFRs in MVEs that are significantly smaller than control (PMID:16554368). Supporting Evidence: PMID:16554368 Electron microscopy of hVps24-depleted cells showed an accumulation of EGFRs in MVEs that were significantly smaller than those in control cells |
| GO:0090148 membrane fission | IDA PMID:36604498 Structural basis of CHMP2A-CHMP3 ESCRT-III polymer assembly ... | ACCEPT | Summary: Direct experimental evidence for CHMP3 role in membrane fission. Reason: Core ESCRT-III function. CHMP3 co-polymerizes with CHMP2A to drive membrane scission. Supporting Evidence: PMID:36604498 Epub 2023 Jan 5. Structural basis of CHMP2A-CHMP3 ESCRT-III polymer assembly and membrane cleavage. |
| GO:0180020 membrane bending activity | IDA PMID:36604498 Structural basis of CHMP2A-CHMP3 ESCRT-III polymer assembly ... | ACCEPT | Summary: CHMP3 contributes to membrane bending as part of ESCRT-III polymers. Reason: ESCRT-III polymers bend and constrict membranes. The helical CHMP2A-CHMP3 structures can deform membranes (PMID:18687924). Supporting Evidence: PMID:18687924 We found that the ESCRT-III proteins CHMP2A and CHMP3...could assemble in vitro into helical tubular structures that expose their membrane interaction sites on the outside of the tubule PMID:36604498 Epub 2023 Jan 5. Structural basis of CHMP2A-CHMP3 ESCRT-III polymer assembly and membrane cleavage. |
| GO:0000421 autophagosome membrane | IDA PMID:17984323 Functional multivesicular bodies are required for autophagic... | ACCEPT | Summary: CHMP3 localizes to autophagosome membranes. Reason: ESCRT-III is required for autophagy and autophagic clearance. Supporting Evidence: PMID:17984323 Functional multivesicular bodies are required for autophagic clearance of protein aggregates associated with neurodegenerative disease. |
| GO:0000776 kinetochore | IDA PMID:26040712 Spastin and ESCRT-III coordinate mitotic spindle disassembly... | ACCEPT | Summary: Direct evidence for CHMP3 localization to kinetochores. Reason: Global screen identified CHMP3 at kinetochores (cited in PMID:20616062). Secondary localization related to mitotic functions. Supporting Evidence: PMID:20616062 CHMP3 and CHMP4, were recently reported to localize to kinetochores in a global screen for proteins with possible mitotic functions PMID:26040712 Spastin and ESCRT-III coordinate mitotic spindle disassembly and nuclear envelope sealing. |
| GO:0001778 plasma membrane repair | IDA PMID:24482116 ESCRT machinery is required for plasma membrane repair. | ACCEPT | Summary: Direct evidence that ESCRT machinery including CHMP3 is required for plasma membrane repair. Reason: ESCRT-III mediates membrane resealing after injury. This is a topologically equivalent membrane fusion event to other ESCRT functions. Supporting Evidence: PMID:24482116 ESCRT machinery is required for plasma membrane repair |
| GO:0005765 lysosomal membrane | IDA PMID:17984323 Functional multivesicular bodies are required for autophagic... | ACCEPT | Summary: CHMP3 localizes to lysosomal membranes during autophagy-related processes. Reason: ESCRT-III is involved in autophagosome-lysosome fusion and lysosomal microautophagy. Supporting Evidence: PMID:17984323 Functional multivesicular bodies are required for autophagic clearance of protein aggregates associated with neurodegenerative disease. |
| GO:0005828 kinetochore microtubule | IDA PMID:26040712 Spastin and ESCRT-III coordinate mitotic spindle disassembly... | KEEP AS NON CORE | Summary: CHMP3 has been found at kinetochore microtubules. Reason: Secondary localization. Related to mitotic functions of ESCRT-III but not a core function. Supporting Evidence: PMID:26040712 Spastin and ESCRT-III coordinate mitotic spindle disassembly and nuclear envelope sealing. |
| GO:0005886 plasma membrane | IDA PMID:24878737 Structure of cellular ESCRT-III spirals and their relationsh... | ACCEPT | Summary: CHMP3 localizes to plasma membrane during viral budding. Reason: ESCRT-III spirals form at plasma membrane during HIV-1 budding. Supporting Evidence: PMID:24878737 Structure of cellular ESCRT-III spirals and their relationship to HIV budding |
| GO:0006914 autophagy | IMP PMID:17984323 Functional multivesicular bodies are required for autophagic... | ACCEPT | Summary: Mutant phenotype evidence for CHMP3 role in autophagy. Reason: Functional MVBs are required for autophagic clearance. ESCRT dysfunction impairs autophagy. Supporting Evidence: PMID:17984323 Functional multivesicular bodies are required for autophagic clearance of protein aggregates |
| GO:0006997 nucleus organization | IMP PMID:20616062 Human ESCRT-III and VPS4 proteins are required for centrosom... | ACCEPT | Summary: CHMP3 depletion causes nuclear morphology defects. Reason: ESCRT-III depletion causes defects in chromosome segregation and nuclear morphology (PMID:20616062). Supporting Evidence: PMID:20616062 causing defects in chromosome segregation and nuclear morphology |
| GO:0006997 nucleus organization | IMP NOT PMID:20616062 Human ESCRT-III and VPS4 proteins are required for centrosom... | ACCEPT | Summary: NOT annotation per GOA (UniProt) indicating CHMP3 is not directly involved in nucleus organization. Reason: GOA includes a NOT qualifier for this term with the same PMID; capture the negative annotation alongside the positive ComplexPortal entry. Supporting Evidence: PMID:20616062 Human ESCRT-III and VPS4 proteins are required for centrosome and spindle maintenance. |
| GO:0007080 mitotic metaphase chromosome alignment | IMP PMID:20616062 Human ESCRT-III and VPS4 proteins are required for centrosom... | KEEP AS NON CORE | Summary: CHMP3 depletion affects chromosome alignment. Reason: Secondary effect of ESCRT-III depletion on mitotic processes. Related to centrosome/spindle maintenance roles. Supporting Evidence: PMID:20616062 causing defects in chromosome segregation |
| GO:0007080 mitotic metaphase chromosome alignment | IMP NOT PMID:20616062 Human ESCRT-III and VPS4 proteins are required for centrosom... | ACCEPT | Summary: NOT annotation per GOA (UniProt) indicating CHMP3 is not directly involved in mitotic metaphase chromosome alignment. Reason: GOA includes a NOT qualifier for this term with the same PMID; capture the negative annotation alongside the positive ComplexPortal entry. Supporting Evidence: PMID:20616062 Human ESCRT-III and VPS4 proteins are required for centrosome and spindle maintenance. |
| GO:0030496 midbody | IDA PMID:26040712 Spastin and ESCRT-III coordinate mitotic spindle disassembly... | ACCEPT | Summary: Direct evidence for CHMP3 localization to midbody. Reason: ESCRT-III proteins including CHMP3 localize to the midbody during cytokinesis to mediate abscission. Supporting Evidence: PMID:20616062 VPS4 proteins concentrated at spindle poles during mitosis and then at midbodies during cytokinesis PMID:26040712 Spastin and ESCRT-III coordinate mitotic spindle disassembly and nuclear envelope sealing. |
| GO:0031468 nuclear membrane reassembly | IMP PMID:26040713 ESCRT-III controls nuclear envelope reformation. | ACCEPT | Summary: ESCRT-III including CHMP3 is required for nuclear envelope reformation. Reason: ESCRT-III controls nuclear envelope reformation by sealing holes in the forming NE (PMID:26040713). CHMP3 depletion impairs NE integrity. Supporting Evidence: PMID:26040713 However, in CHMP2A-, CHMP3- or UFD1-depleted cells, the post-mitotic nucleo-cytoplasmic partitioning of GFP-NLS-Ξ²Gal was reduced...indicating that NE integrity was compromised |
| GO:0032585 multivesicular body membrane | IDA PMID:16554368 The ESCRT-III subunit hVps24 is required for degradation but... | ACCEPT | Summary: Direct evidence for CHMP3 localization to MVB membranes. Reason: hVps24 localizes to late endosomes/MVBs (PMID:16554368). Supporting Evidence: PMID:16554368 Electron microscopy of hVps24-depleted cells showed an accumulation of EGFRs in MVEs |
| GO:0036258 multivesicular body assembly | NAS PMID:16505166 Recycling of ESCRTs by the AAA-ATPase Vps4 is regulated by a... | ACCEPT | Summary: CHMP3 functions in MVB assembly as an ESCRT-III component. Reason: Core ESCRT-III function in ILV formation within MVBs. Supporting Evidence: PMID:16505166 Recycling of ESCRTs by the AAA-ATPase Vps4 is regulated by a conserved VSL region in Vta1. |
| GO:0039702 viral budding via host ESCRT complex | IDA PMID:24878737 Structure of cellular ESCRT-III spirals and their relationsh... | ACCEPT | Summary: Direct evidence for CHMP3 function in viral budding. Reason: Structural and functional studies show CHMP3 is part of ESCRT-III assemblies mediating HIV-1 budding. Supporting Evidence: PMID:24878737 Structure of cellular ESCRT-III spirals and their relationship to HIV budding |
| 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: CHMP3 functions in ubiquitin-dependent cargo degradation via MVBs. Reason: ESCRT-III is required for sorting ubiquitinated cargo to lysosomes. This is a core ESCRT-III function. Supporting Evidence: PMID:17984323 Functional multivesicular bodies are required for autophagic clearance of protein aggregates associated with neurodegenerative disease. |
| GO:0046761 viral budding from plasma membrane | IDA PMID:24878737 Structure of cellular ESCRT-III spirals and their relationsh... | ACCEPT | Summary: Direct evidence for CHMP3 role in viral budding from plasma membrane. Reason: HIV-1 buds from plasma membrane using ESCRT-III machinery including CHMP3. Supporting Evidence: PMID:24878737 Structure of cellular ESCRT-III spirals and their relationship to HIV budding. |
| GO:0051469 vesicle fusion with vacuole | NAS PMID:16505166 Recycling of ESCRTs by the AAA-ATPase Vps4 is regulated by a... | ACCEPT | Summary: CHMP3 may function in vesicle fusion with vacuole (lysosome). Reason: MVB-lysosome fusion is impaired upon hVps24 depletion (PMID:16554368). Supporting Evidence: PMID:16554368 impaired fusion with lyso-bisphosphatidic acid-positive late endosomes/lysosomes PMID:16505166 Recycling of ESCRTs by the AAA-ATPase Vps4 is regulated by a conserved VSL region in Vta1. |
| GO:0061763 multivesicular body-lysosome fusion | NAS PMID:16505166 Recycling of ESCRTs by the AAA-ATPase Vps4 is regulated by a... | ACCEPT | Summary: CHMP3 is required for MVB-lysosome fusion. Reason: hVps24 depletion causes accumulation of MVBs with impaired lysosome fusion (PMID:16554368). Supporting Evidence: PMID:16554368 impaired fusion with lyso-bisphosphatidic acid-positive late endosomes/lysosomes PMID:16505166 Recycling of ESCRTs by the AAA-ATPase Vps4 is regulated by a conserved VSL region in Vta1. |
| GO:0061952 midbody abscission | IMP PMID:20616062 Human ESCRT-III and VPS4 proteins are required for centrosom... | ACCEPT | Summary: Mutant phenotype evidence for CHMP3 role in midbody abscission. Reason: Systematic analysis showed CHMP3 depletion inhibits abscission. Supporting Evidence: PMID:20616062 depletion of VPS4A, VPS4B, or any of the 11 different human ESCRT-III (CHMP) proteins inhibited abscission |
| GO:0071985 multivesicular body sorting pathway | IDA PMID:16554368 The ESCRT-III subunit hVps24 is required for degradation but... | ACCEPT | Summary: Direct evidence for CHMP3 function in MVB sorting pathway. Reason: Core ESCRT-III function demonstrated by hVps24 depletion studies. Supporting Evidence: PMID:16554368 The ESCRT-III subunit hVps24 is required for degradation |
| GO:0090148 membrane fission | NAS PMID:19234443 Membrane scission by the ESCRT-III complex. | ACCEPT | Summary: CHMP3 functions in membrane fission as part of ESCRT-III. Reason: Core ESCRT-III function in membrane scission across multiple contexts. Supporting Evidence: PMID:19234443 Membrane scission by the ESCRT-III complex |
| GO:0097352 autophagosome maturation | IMP PMID:17984323 Functional multivesicular bodies are required for autophagic... | ACCEPT | Summary: ESCRT-III function is required for autophagosome maturation. Reason: Functional MVBs are required for autophagic clearance. Supporting Evidence: PMID:17984323 Functional multivesicular bodies are required for autophagic clearance |
| 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: CHMP3 depletion affects spindle assembly. Reason: Secondary effect of ESCRT-III on centrosome/spindle maintenance. Depletion produces multipolar spindles. Supporting Evidence: PMID:20616062 producing multipolar spindles (most ESCRT-III/VPS4 proteins) |
| GO:1901673 regulation of mitotic spindle assembly | IMP NOT PMID:20616062 Human ESCRT-III and VPS4 proteins are required for centrosom... | ACCEPT | Summary: NOT annotation per GOA (UniProt) indicating CHMP3 is not directly involved in regulation of mitotic spindle assembly. Reason: GOA includes a NOT qualifier for this term with the same PMID; capture the negative annotation alongside the positive ComplexPortal entry. Supporting Evidence: PMID:20616062 Human ESCRT-III and VPS4 proteins are required for centrosome and spindle maintenance. |
| GO:1902774 late endosome to lysosome transport | IMP PMID:17984323 Functional multivesicular bodies are required for autophagic... | ACCEPT | Summary: CHMP3 is required for late endosome to lysosome transport. Reason: Core function. hVps24 depletion impairs MVB-lysosome fusion. Supporting Evidence: PMID:16554368 impaired fusion with lyso-bisphosphatidic acid-positive late endosomes/lysosomes PMID:17984323 Functional multivesicular bodies are required for autophagic clearance of protein aggregates associated with neurodegenerative disease. |
| GO:1904930 amphisome membrane | IDA PMID:17984323 Functional multivesicular bodies are required for autophagic... | ACCEPT | Summary: CHMP3 localizes to amphisome membranes. Reason: ESCRT-III is required for autophagy which involves amphisome formation. Supporting Evidence: PMID:17984323 Functional multivesicular bodies are required for autophagic clearance of protein aggregates associated with neurodegenerative disease. |
| GO:0140678 molecular function inhibitor activity | EXP PMID:21827950 Structural basis for ESCRT-III CHMP3 recruitment of AMSH. | MARK AS OVER ANNOTATED | Summary: CHMP3 has been annotated with molecular function inhibitor activity based on its recruitment of AMSH (STAMBP) which acts as a deubiquitinase. Reason: This term is too general and does not capture the specific biological role. CHMP3 recruits AMSH/STAMBP which has deubiquitinase activity, but CHMP3 itself is not an inhibitor. The structural interaction is better described by specific protein binding terms. Supporting Evidence: PMID:21827950 Structural basis for ESCRT-III CHMP3 recruitment of AMSH |
| GO:0046761 viral budding from plasma membrane | IMP PMID:14505570 The protein network of HIV budding. | ACCEPT | Summary: Mutant phenotype evidence for CHMP3 role in viral budding. Reason: Dominant-negative CHMP mutants arrest HIV-1 budding. Supporting Evidence: PMID:14505570 dominant-negative mutants of late-acting human class E proteins arrested HIV-1 budding |
| GO:0000815 ESCRT III complex | IDA PMID:18687924 Helical structures of ESCRT-III are disassembled by VPS4. | ACCEPT | Summary: Direct structural evidence for CHMP3 as ESCRT-III component. Reason: Crystal structures and EM show CHMP2A-CHMP3 helical copolymers. Supporting Evidence: PMID:18687924 We found that the ESCRT-III proteins CHMP2A and CHMP3...could assemble in vitro into helical tubular structures |
| GO:0005515 protein binding | IPI PMID:18687924 Helical structures of ESCRT-III are disassembled by VPS4. | MODIFY | Summary: Protein binding annotation based on CHMP2A-CHMP3 interaction. Reason: "Protein binding" is too vague and uninformative. The specific interaction is CHMP2A binding to form helical polymers. More specific terms should be used. Proposed replacements: identical protein binding Supporting Evidence: PMID:18687924 Aug 7. Helical structures of ESCRT-III are disassembled by VPS4. |
| GO:0016236 macroautophagy | TAS PMID:20588296 Membrane budding and scission by the ESCRT machinery: it's a... | ACCEPT | Summary: CHMP3 functions in macroautophagy as part of ESCRT-III. Reason: ESCRT-III is required for autophagy. MVBs fuse with autophagosomes. Supporting Evidence: PMID:20588296 Jun 30. Membrane budding and scission by the ESCRT machinery: it's all in the neck. |
| GO:0061763 multivesicular body-lysosome fusion | IMP PMID:16554368 The ESCRT-III subunit hVps24 is required for degradation but... | ACCEPT | Summary: Mutant phenotype evidence for CHMP3 role in MVB-lysosome fusion. Reason: hVps24 depletion causes MVBs to accumulate with impaired lysosome fusion. Supporting Evidence: PMID:16554368 impaired fusion with lyso-bisphosphatidic acid-positive late endosomes/lysosomes |
| GO:2000641 regulation of early endosome to late endosome transport | IMP PMID:16554368 The ESCRT-III subunit hVps24 is required for degradation but... | ACCEPT | Summary: CHMP3 regulates early to late endosome transport. Reason: hVps24 is required for transport of EGFR from early endosomes to late endosomes/lysosomes. Supporting Evidence: PMID:16554368 transport of the receptor from early endosomes to lysosomes |
| GO:0005770 late endosome | IDA PMID:16554368 The ESCRT-III subunit hVps24 is required for degradation but... | ACCEPT | Summary: Direct evidence for CHMP3 localization to late endosomes. Reason: Primary localization site for endogenous hVps24. Supporting Evidence: PMID:16554368 Like Tsg101, endogenous hVps24 localized mainly to late endosomes. |
| GO:0000815 ESCRT III complex | TAS PMID:20588296 Membrane budding and scission by the ESCRT machinery: it's a... | ACCEPT | Summary: TAS evidence for CHMP3 as ESCRT-III component. Reason: Well-established core function. Supporting Evidence: PMID:20588296 Jun 30. Membrane budding and scission by the ESCRT machinery: it's all in the neck. |
| GO:0036258 multivesicular body assembly | TAS PMID:20588296 Membrane budding and scission by the ESCRT machinery: it's a... | ACCEPT | Summary: CHMP3 functions in MVB assembly. Reason: Core ESCRT-III function. Supporting Evidence: PMID:20588296 Jun 30. Membrane budding and scission by the ESCRT machinery: it's all in the neck. |
| GO:0039702 viral budding via host ESCRT complex | TAS PMID:20588296 Membrane budding and scission by the ESCRT machinery: it's a... | ACCEPT | Summary: CHMP3 functions in viral budding. Reason: Well-established ESCRT-III function hijacked by viruses. Supporting Evidence: PMID:20588296 Jun 30. Membrane budding and scission by the ESCRT machinery: it's all in the neck. |
| GO:0000815 ESCRT III complex | TAS PMID:21118109 The role of ESCRT proteins in fusion events involving lysoso... | ACCEPT | Summary: Additional TAS evidence for ESCRT-III membership. Reason: Core function. Supporting Evidence: PMID:21118109 The role of ESCRT proteins in fusion events involving lysosomes, endosomes and autophagosomes. |
| GO:0071985 multivesicular body sorting pathway | TAS PMID:21118109 The role of ESCRT proteins in fusion events involving lysoso... | ACCEPT | Summary: TAS evidence for MVB sorting pathway function. Reason: Core ESCRT-III function. Supporting Evidence: PMID:21118109 The role of ESCRT proteins in fusion events involving lysosomes, endosomes and autophagosomes. |
| GO:0097352 autophagosome maturation | TAS PMID:21118109 The role of ESCRT proteins in fusion events involving lysoso... | ACCEPT | Summary: TAS evidence for role in autophagosome maturation. Reason: ESCRT-III is required for autophagy. Supporting Evidence: PMID:21118109 The role of ESCRT proteins in fusion events involving lysosomes, endosomes and autophagosomes. |
| GO:0005515 protein binding | IPI PMID:18385515 Novel interactions of ESCRT-III with LIP5 and VPS4 and their... | MODIFY | Summary: Protein binding based on interactions with LIP5 and VPS4. Reason: "Protein binding" is uninformative. Specific interactions with LIP5/VTA1 and VPS4 should be captured with more specific terms. Proposed replacements: identical protein binding Supporting Evidence: PMID:18385515 Apr 2. Novel interactions of ESCRT-III with LIP5 and VPS4 and their implications for ESCRT-III disassembly. |
| GO:0005515 protein binding | IPI PMID:23105106 Interactions of the human LIP5 regulatory protein with endos... | MODIFY | Summary: Protein binding based on LIP5 interactions. Reason: "Protein binding" is too vague. Proposed replacements: identical protein binding Supporting Evidence: PMID:23105106 2012 Oct 26. Interactions of the human LIP5 regulatory protein with endosomal sorting complexes required for transport. |
| GO:0000815 ESCRT III complex | IDA PMID:24878737 Structure of cellular ESCRT-III spirals and their relationsh... | ACCEPT | Summary: Direct evidence for ESCRT-III complex membership from structural studies. Reason: Core function. Supporting Evidence: PMID:24878737 Structure of cellular ESCRT-III spirals |
| GO:0005515 protein binding | IPI PMID:23051622 ESCRT-III CHMP2A and CHMP3 form variable helical polymers in... | MODIFY | Summary: Protein binding annotation. Reason: "Protein binding" is uninformative. Should specify the binding partner. Proposed replacements: identical protein binding Supporting Evidence: PMID:23051622 ESCRT-III CHMP2A and CHMP3 form variable helical polymers in vitro and act synergistically during HIV-1 budding. |
| GO:0005886 plasma membrane | IDA PMID:16740483 Structural basis for budding by the ESCRT-III factor CHMP3. | ACCEPT | Summary: CHMP3 localizes to plasma membrane during viral budding and ESCRT function. Reason: ESCRT-III assembles at plasma membrane for membrane fission events. Supporting Evidence: PMID:16740483 Structural basis for budding by the ESCRT-III factor CHMP3 |
| GO:0019076 viral release from host cell | IMP PMID:23051622 ESCRT-III CHMP2A and CHMP3 form variable helical polymers in... | ACCEPT | Summary: CHMP3 functions in viral release from host cells. Reason: ESCRT-III is required for enveloped virus budding and release. Supporting Evidence: PMID:23051622 ESCRT-III CHMP2A and CHMP3 form variable helical polymers in vitro and act synergistically during HIV-1 budding. |
| GO:0019076 viral release from host cell | IGI PMID:23051622 ESCRT-III CHMP2A and CHMP3 form variable helical polymers in... | ACCEPT | Summary: Genetic interaction evidence for role in viral release. Reason: ESCRT-III function in viral budding. Supporting Evidence: PMID:23051622 ESCRT-III CHMP2A and CHMP3 form variable helical polymers in vitro and act synergistically during HIV-1 budding. |
| GO:0031210 phosphatidylcholine binding | IMP PMID:18687924 Helical structures of ESCRT-III are disassembled by VPS4. | ACCEPT | Summary: CHMP3 binds phosphatidylcholine in membrane targeting. Reason: CHMP2A-CHMP3 copolymers show cooperative membrane targeting. UniProt notes selective binding to phosphoinositides including PtdIns(3,5)P2. Supporting Evidence: PMID:18687924 CHMP2A and CHMP3 copolymerized in solution, and their membrane targeting was cooperatively enhanced on planar lipid bilayers |
| GO:0031410 cytoplasmic vesicle | IDA PMID:16740483 Structural basis for budding by the ESCRT-III factor CHMP3. | ACCEPT | Summary: CHMP3 localizes to cytoplasmic vesicles. Reason: CHMP3 associates with various vesicular compartments. Supporting Evidence: PMID:16740483 Structural basis for budding by the ESCRT-III factor CHMP3. |
| GO:0039702 viral budding via host ESCRT complex | IMP PMID:16740483 Structural basis for budding by the ESCRT-III factor CHMP3. | ACCEPT | Summary: Mutant phenotype evidence for CHMP3 role in viral budding. Reason: CHMP3 structural studies show basis for budding function. Supporting Evidence: PMID:16740483 Structural basis for budding by the ESCRT-III factor CHMP3 |
| GO:0039702 viral budding via host ESCRT complex | IMP PMID:23051622 ESCRT-III CHMP2A and CHMP3 form variable helical polymers in... | ACCEPT | Summary: Additional mutant phenotype evidence for viral budding role. Reason: Core ESCRT-III function. Supporting Evidence: PMID:23051622 ESCRT-III CHMP2A and CHMP3 form variable helical polymers in vitro and act synergistically during HIV-1 budding. |
| GO:0044790 suppression of viral release by host | IMP PMID:16740483 Structural basis for budding by the ESCRT-III factor CHMP3. | ACCEPT | Summary: Overexpression of CHMP3 suppresses HIV-1 release. Reason: UniProt notes that CHMP3 overexpression strongly inhibits HIV-1 release. This reflects the ability of excess ESCRT-III to block normal viral budding. Supporting Evidence: PMID:16740483 Structural basis for budding by the ESCRT-III factor CHMP3 |
| GO:0051258 protein polymerization | IDA PMID:23051622 ESCRT-III CHMP2A and CHMP3 form variable helical polymers in... | ACCEPT | Summary: CHMP3 participates in ESCRT-III polymerization. Reason: CHMP2A-CHMP3 form helical polymers (PMID:18687924). Supporting Evidence: PMID:18687924 We found that the ESCRT-III proteins CHMP2A and CHMP3...could assemble in vitro into helical tubular structures PMID:23051622 ESCRT-III CHMP2A and CHMP3 form variable helical polymers in vitro and act synergistically during HIV-1 budding. |
| GO:1990381 ubiquitin-specific protease binding | IPI PMID:18395747 Structural basis for autoinhibition of ESCRT-III CHMP3. | ACCEPT | Summary: CHMP3 binds STAMBP/AMSH, a ubiquitin-specific protease. Reason: CHMP3 interacts with STAMBP to recruit deubiquitinase activity to ESCRT-III. Well-characterized interaction. Supporting Evidence: PMID:18395747 Structural basis for autoinhibition of ESCRT-III CHMP3 |
| GO:0010824 regulation of centrosome duplication | IMP PMID:20616062 Human ESCRT-III and VPS4 proteins are required for centrosom... | KEEP AS NON CORE | Summary: CHMP3 depletion affects centrosome numbers. Reason: ESCRT-III depletion causes centrosome amplification. Secondary function. Supporting Evidence: PMID:20616062 depletion of individual ESCRT-III and VPS4 proteins also altered centrosome and spindle pole numbers |
| GO:1903541 regulation of exosomal secretion | IMP NOT PMID:22660413 Syndecan-syntenin-ALIX regulates the biogenesis of exosomes. | ACCEPT | Summary: NOT annotation per GOA indicating CHMP3 is not directly involved in regulation of exosomal secretion. Reason: GOA includes a NOT qualifier for this term with PMID:22660413; we accept the negative annotation. Supporting Evidence: PMID:22660413 Syndecan-syntenin-ALIX regulates the biogenesis of exosomes |
| GO:0005515 protein binding | IPI PMID:14519844 Divergent retroviral late-budding domains recruit vacuolar p... | MODIFY | Summary: Protein binding based on VPS4A interaction. Reason: "Protein binding" is uninformative. Specific interaction with VPS4A should be captured. Proposed replacements: identical protein binding Supporting Evidence: PMID:14519844 Divergent retroviral late-budding domains recruit vacuolar protein sorting factors by using alternative adaptor proteins. |
| GO:0005515 protein binding | IPI PMID:14505570 The protein network of HIV budding. | MODIFY | Summary: Protein binding based on CHMP4A interaction. Reason: "Protein binding" is uninformative. Proposed replacements: identical protein binding Supporting Evidence: PMID:14505570 The protein network of HIV budding. |
| GO:0070062 extracellular exosome | HDA PMID:19056867 Large-scale proteomics and phosphoproteomics of urinary exos... | ACCEPT | Summary: CHMP3 detected in extracellular exosomes by proteomics. Reason: ESCRT-III components can be found in exosomes, possibly reflecting their role in ILV/exosome biogenesis. Supporting Evidence: PMID:19056867 Large-scale proteomics and phosphoproteomics of urinary exosomes |
| GO:0005829 cytosol | TAS Reactome:R-HSA-3159232 | ACCEPT | Summary: Reactome annotation for cytosolic localization (HIV virion budding). Reason: CHMP3 exists in autoinhibited form in cytosol. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-917693 | ACCEPT | Summary: Reactome annotation for cytosolic localization (ESCRT disassembly). Reason: Cytosolic pool of CHMP3. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-917700 | ACCEPT | Summary: Reactome annotation for cytosolic localization (MVB vesicle formation). Reason: Cytosolic pool of CHMP3. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9668389 | ACCEPT | Summary: Reactome annotation for cytosolic localization (NE reformation). Reason: Cytosolic pool of CHMP3. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9668395 | ACCEPT | Summary: Reactome annotation for cytosolic localization. Reason: Cytosolic pool of CHMP3. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9668398 | ACCEPT | Summary: Reactome annotation for cytosolic localization. Reason: Cytosolic pool of CHMP3. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9668405 | ACCEPT | Summary: Reactome annotation for cytosolic localization. Reason: Cytosolic pool of CHMP3. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9668415 | ACCEPT | Summary: Reactome annotation for cytosolic localization. Reason: Cytosolic pool of CHMP3. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9668419 | ACCEPT | Summary: Reactome annotation for cytosolic localization. Reason: Cytosolic pool of CHMP3. |
| GO:0005515 protein binding | IPI PMID:21543490 Mechanism of inhibition of retrovirus release from cells by ... | MODIFY | Summary: Protein binding based on VTA1/VPS4A interaction. Reason: "Protein binding" is uninformative. Proposed replacements: identical protein binding Supporting Evidence: PMID:21543490 Mechanism of inhibition of retrovirus release from cells by interferon-induced gene ISG15. |
| GO:0005515 protein binding | IPI PMID:19525971 Structural basis for ESCRT-III protein autoinhibition. | MODIFY | Summary: Protein binding from autoinhibition structural study. Reason: "Protein binding" is uninformative. This study characterized CHMP2A interaction and autoinhibition. Proposed replacements: identical protein binding Supporting Evidence: PMID:19525971 Jun 14. Structural basis for ESCRT-III protein autoinhibition. |
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Download this section (compressed HTML)Q: What is the precise sequence of CHMP subunit assembly and VPS4-driven remodeling during membrane scission?
Q: How do different ESCRT-III paralogs contribute to compartment-specific functions (MVB vs. lysosomal microautophagy)?
Q: What regulates CHMP3 recruitment to different cellular sites (endosomes vs. midbody vs. nuclear envelope)?
Experiment: Live-cell imaging of CHMP3 dynamics during nuclear envelope reformation at higher temporal resolution
Experiment: Systematic comparison of CHMP3 knockout vs knockdown phenotypes to assess functional redundancy
Experiment: Reconstitution of CHMP3-containing ESCRT-III assemblies with defined subunit stoichiometry
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