CHMP2A

Existing Annotations Review

GO Term	Evidence	Action	Reason
GO:0000815 ESCRT III complex	IBA GO_REF:0000033	ACCEPT	Summary: CHMP2A is a core ESCRT-III subunit that copolymerizes with CHMP3. Reason: Definitional - CHMP2A is a bona fide ESCRT-III subunit (PMID:18687924). Supporting Evidence: PMID:18687924 We found that the ESCRT-III proteins CHMP2A and CHMP3 (charged multivesicular body proteins 2A and 3) could assemble in vitro into helical tubular structures file:human/CHMP2A/CHMP2A-deep-research-falcon.md model: Edison Scientific Literature
GO:0000815 ESCRT III complex	IDA PMID:18687924 Helical structures of ESCRT-III are disassembled by VPS4.	ACCEPT	Summary: Direct evidence for CHMP2A-CHMP3 copolymerization. Reason: Core function confirmed by structural studies. Supporting Evidence: PMID:18687924 Aug 7. Helical structures of ESCRT-III are disassembled by VPS4.
GO:0000815 ESCRT III complex	IDA PMID:26040712 Spastin and ESCRT-III coordinate mitotic spindle disassembly...	ACCEPT	Summary: ESCRT-III localization confirmed during NE sealing. Reason: Core function confirmed. Supporting Evidence: PMID:26040712 Spastin and ESCRT-III coordinate mitotic spindle disassembly and nuclear envelope sealing.
GO:0000815 ESCRT III complex	TAS PMID:20588296 Membrane budding and scission by the ESCRT machinery: it's a...	ACCEPT	Summary: ESCRT-III role in membrane scission reviewed. Reason: Core complex membership. Supporting Evidence: PMID:20588296 Jun 30. Membrane budding and scission by the ESCRT machinery: it's all in the neck.
GO:0005771 multivesicular body	IBA GO_REF:0000033	ACCEPT	Summary: CHMP2A localizes to MVB membranes during ILV formation. Reason: Core localization supported by literature (PMID:16554368).
GO:0032585 multivesicular body membrane	IDA PMID:16554368 The ESCRT-III subunit hVps24 is required for degradation but...	ACCEPT	Summary: ESCRT-III localizes to MVB membranes. Reason: Core localization - endogenous hVps24 localized to late endosomes. Supporting Evidence: PMID:16554368 Mar 22. The ESCRT-III subunit hVps24 is required for degradation but not silencing of the epidermal growth factor receptor.
GO:0032585 multivesicular body membrane	IEA GO_REF:0000117	ACCEPT	Summary: ESCRT-III localization to MVB membrane. Reason: Consistent with core function.
GO:0071985 multivesicular body sorting pathway	IDA PMID:16554368 The ESCRT-III subunit hVps24 is required for degradation but...	ACCEPT	Summary: CHMP2A functions in MVB sorting. Reason: Core function - hVps24 depletion impairs EGFR degradation. Supporting Evidence: PMID:16554368 Mar 22. The ESCRT-III subunit hVps24 is required for degradation but not silencing of the epidermal growth factor receptor.
GO:0071985 multivesicular body sorting pathway	IEA GO_REF:0000117	ACCEPT	Summary: ESCRT-III required for MVB sorting. Reason: Core function.
GO:0032509 endosome transport via multivesicular body sorting pathway	IBA GO_REF:0000033	ACCEPT	Summary: CHMP2A required for MVB-mediated transport. Reason: Core function of ESCRT-III.
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: ESCRT-III sorts ubiquitinated cargo for degradation. Reason: Core function. Supporting Evidence: PMID:17984323 Functional multivesicular bodies are required for autophagic clearance of protein aggregates associated with neurodegenerative disease.
GO:0043162 ubiquitin-dependent protein catabolic process via the multivesicular body sorting pathway	IEA GO_REF:0000117	ACCEPT	Summary: ESCRT-III required for ubiquitinated cargo degradation. Reason: Core function.
GO:0036258 multivesicular body assembly	TAS PMID:20588296 Membrane budding and scission by the ESCRT machinery: it's a...	ACCEPT	Summary: ESCRT-III is required for MVB assembly. Reason: 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	NAS PMID:16505166 Recycling of ESCRTs by the AAA-ATPase Vps4 is regulated by a...	ACCEPT	Summary: ESCRT function required for MVB assembly. Reason: Core function. Supporting Evidence: PMID:16505166 Recycling of ESCRTs by the AAA-ATPase Vps4 is regulated by a conserved VSL region in Vta1.
GO:0045324 late endosome to vacuole transport	IBA GO_REF:0000033	ACCEPT	Summary: CHMP2A functions in late endosome maturation. Reason: ESCRT-III required for MVE-lysosome fusion (PMID:16554368).
GO:1902774 late endosome to lysosome transport	IMP PMID:17984323 Functional multivesicular bodies are required for autophagic...	ACCEPT	Summary: ESCRT-III required for late endosome to lysosome transport. Reason: Core function. Supporting Evidence: PMID:17984323 Functional multivesicular bodies are required for autophagic clearance of protein aggregates associated with neurodegenerative disease.
GO:1902774 late endosome to lysosome transport	IEA GO_REF:0000117	ACCEPT	Summary: ESCRT-III required for late endosome to lysosome transport. Reason: Core function.
GO:0061763 multivesicular body-lysosome fusion	NAS PMID:16505166 Recycling of ESCRTs by the AAA-ATPase Vps4 is regulated by a...	ACCEPT	Summary: ESCRT function required for MVB-lysosome fusion. Reason: Core function. Supporting Evidence: 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: CHMP2A required for cytokinetic abscission. Reason: Core function - ESCRT-III depletion inhibits abscission. Supporting Evidence: PMID:20616062 We found that 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: CHMP2A required for cytokinetic abscission. Reason: Core function.
GO:0030496 midbody	IDA PMID:26040712 Spastin and ESCRT-III coordinate mitotic spindle disassembly...	ACCEPT	Summary: ESCRT-III localizes to midbody during cytokinesis. Reason: Core localization for abscission function. Supporting Evidence: PMID:26040712 Spastin and ESCRT-III coordinate mitotic spindle disassembly and nuclear envelope sealing.
GO:0030496 midbody	IEA GO_REF:0000117	ACCEPT	Summary: ESCRT-III localizes to midbody. Reason: Core localization.
GO:0031468 nuclear membrane reassembly	IMP PMID:26040712 Spastin and ESCRT-III coordinate mitotic spindle disassembly...	ACCEPT	Summary: ESCRT-III required for NE sealing during mitotic exit. Reason: Core function. Supporting Evidence: PMID:26040712 We propose that ESCRT-III, VPS4 and spastin cooperate to coordinate nuclear envelope sealing and spindle disassembly
GO:0031468 nuclear membrane reassembly	IMP PMID:26040713 ESCRT-III controls nuclear envelope reformation.	ACCEPT	Summary: ESCRT-III required for NE sealing. Reason: Core function. Supporting Evidence: PMID:26040713 The ESCRT-III component charged multivesicular body protein 2A (CHMP2A) is directed to the forming NE through binding to CHMP4B, and provides an activity essential for NE reformation.
GO:0031468 nuclear membrane reassembly	IEA GO_REF:0000117	ACCEPT	Summary: ESCRT-III required for nuclear membrane reassembly. Reason: Core function.
GO:0005635 nuclear envelope	IDA PMID:26040712 Spastin and ESCRT-III coordinate mitotic spindle disassembly...	ACCEPT	Summary: ESCRT-III localizes to nuclear envelope during reformation. Reason: Core localization for NE sealing. Supporting Evidence: PMID:26040712 Spastin and ESCRT-III coordinate mitotic spindle disassembly and nuclear envelope sealing.
GO:0005635 nuclear envelope	IEA GO_REF:0000044	ACCEPT	Summary: ESCRT-III localization to nuclear envelope. Reason: Core localization.
GO:0010458 exit from mitosis	IMP PMID:26040712 Spastin and ESCRT-III coordinate mitotic spindle disassembly...	ACCEPT	Summary: ESCRT-III functions during mitotic exit. Reason: Core function. Supporting Evidence: PMID:26040712 Spastin and ESCRT-III coordinate mitotic spindle disassembly and nuclear envelope sealing.
GO:0000785 chromatin	IDA PMID:28242692 LEM2 recruits CHMP7 for ESCRT-mediated nuclear envelope clos...	ACCEPT	Summary: CHMP2A recruited to chromatin disks during NE reformation. Reason: ESCRT-III recruited to anaphase chromatin for NE sealing. Supporting Evidence: PMID:28242692 LEM2 recruits CHMP7 for ESCRT-mediated nuclear envelope closure in fission yeast and human cells.
GO:0039702 viral budding via host ESCRT complex	IDA PMID:24878737 Structure of cellular ESCRT-III spirals and their relationsh...	ACCEPT	Summary: ESCRT-III forms spirals around nascent HIV Gag assemblies. Reason: Core function. Supporting Evidence: PMID:24878737 depleting Vps4 traps ESCRT-III filaments around nascent Gag assemblies
GO:0039702 viral budding via host ESCRT complex	IMP PMID:23051622 ESCRT-III CHMP2A and CHMP3 form variable helical polymers in...	ACCEPT	Summary: CHMP2A required for viral budding. Reason: Core function. Supporting Evidence: PMID:23051622 CHMP3 contributes synergistically to HIV-1 budding, and the CHMP3 contribution is ~ 10-fold more pronounced in concert with CHMP2A than with CHMP2B
GO:0039702 viral budding via host ESCRT complex	TAS PMID:20588296 Membrane budding and scission by the ESCRT machinery: it's a...	ACCEPT	Summary: ESCRT-III involved in viral budding. Reason: Core 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	IEA GO_REF:0000117	ACCEPT	Summary: ESCRT-III required for viral budding. Reason: Core function.
GO:0039702 viral budding via host ESCRT complex	IGI PMID:24107264 ESCRT requirements for EIAV budding.	ACCEPT	Summary: CHMP2A genetic interaction in viral budding. Reason: Core function - EIAV budding requires CHMP2A-VPS4 interactions. Supporting Evidence: PMID:24107264 EIAV budding was inhibited by point mutations that abrogate the direct interactions between ALIX:CHMP4B, CHMP4B:CHMP2A, and CHMP2A:VPS4A/B
GO:0046761 viral budding from plasma membrane	IDA PMID:24878737 Structure of cellular ESCRT-III spirals and their relationsh...	ACCEPT	Summary: ESCRT-III functions at plasma membrane during viral budding. Reason: Core function. Supporting Evidence: PMID:24878737 Structure of cellular ESCRT-III spirals and their relationship to HIV budding.
GO:0046761 viral budding from plasma membrane	IMP PMID:14505570 The protein network of HIV budding.	ACCEPT	Summary: CHMP2A required for HIV-1 budding. Reason: Core function for viral infection. Supporting Evidence: PMID:14505570 dominant-negative mutants of late-acting human class E proteins arrested HIV-1 budding through plasmal and endosomal membranes
GO:0046761 viral budding from plasma membrane	IEA GO_REF:0000117	ACCEPT	Summary: ESCRT-III required for viral budding from PM. Reason: Core function.
GO:0019076 viral release from host cell	IMP PMID:23051622 ESCRT-III CHMP2A and CHMP3 form variable helical polymers in...	ACCEPT	Summary: CHMP2A required for virus release. Reason: Core function for 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:0019076 viral release from host cell	IGI PMID:23051622 ESCRT-III CHMP2A and CHMP3 form variable helical polymers in...	ACCEPT	Summary: Genetic interaction with CHMP4A in viral release. Reason: Core function. 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 with CHMP3 in viral release. Reason: Core function. Supporting Evidence: PMID:23051622 ESCRT-III CHMP2A and CHMP3 form variable helical polymers in vitro and act synergistically during HIV-1 budding.
GO:0097352 autophagosome maturation	IMP PMID:17984323 Functional multivesicular bodies are required for autophagic...	ACCEPT	Summary: ESCRT-III required for autophagosome maturation. Reason: Core function - needed for phagophore closure. Supporting Evidence: PMID:17984323 autophagic degradation is inhibited in cells depleted of ESCRT subunits
GO:0097352 autophagosome maturation	IEA GO_REF:0000117	ACCEPT	Summary: ESCRT required for autophagosome maturation. Reason: Core function.
GO:0006914 autophagy	IMP PMID:17984323 Functional multivesicular bodies are required for autophagic...	ACCEPT	Summary: ESCRT depletion impairs autophagic degradation. Reason: Core function. Supporting Evidence: PMID:17984323 Functional multivesicular bodies are required for autophagic clearance of protein aggregates associated with neurodegenerative disease.
GO:0016236 macroautophagy	TAS PMID:20588296 Membrane budding and scission by the ESCRT machinery: it's a...	ACCEPT	Summary: ESCRT-III required for macroautophagy. Reason: Core function. Supporting Evidence: PMID:20588296 Jun 30. Membrane budding and scission by the ESCRT machinery: it's all in the neck.
GO:0000421 autophagosome membrane	IDA PMID:17984323 Functional multivesicular bodies are required for autophagic...	ACCEPT	Summary: CHMP2A localizes to autophagosome membranes. Reason: Core localization. Supporting Evidence: 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: CHMP2A localizes to amphisome membranes. Reason: ESCRT-III functions at autophagosome-endosome fusion sites. Supporting Evidence: PMID:17984323 Functional multivesicular bodies are required for autophagic clearance of protein aggregates associated with neurodegenerative disease.
GO:1904930 amphisome membrane	IEA GO_REF:0000117	ACCEPT	Summary: ESCRT-III localizes to amphisome membrane. Reason: Core localization.
GO:0001778 plasma membrane repair	IDA PMID:24482116 ESCRT machinery is required for plasma membrane repair.	ACCEPT	Summary: ESCRT machinery required for plasma membrane repair. Reason: Core function - ESCRT proteins recruited within seconds to wounds. Supporting Evidence: PMID:24482116 ESCRT proteins were recruited within seconds to plasma membrane wounds
GO:0001778 plasma membrane repair	IEA GO_REF:0000117	ACCEPT	Summary: ESCRT machinery required for PM repair. Reason: Core function.
GO:0090148 membrane fission	IDA PMID:36604498 Structural basis of CHMP2A-CHMP3 ESCRT-III polymer assembly ...	ACCEPT	Summary: Direct evidence for CHMP2A membrane fission activity. Reason: Core function. Supporting Evidence: PMID:36604498 Epub 2023 Jan 5. Structural basis of CHMP2A-CHMP3 ESCRT-III polymer assembly and membrane cleavage.
GO:0090148 membrane fission	NAS PMID:19234443 Membrane scission by the ESCRT-III complex.	ACCEPT	Summary: ESCRT-III mediates membrane fission. Reason: Core function. Supporting Evidence: PMID:19234443 ESCRT-III has the instrinsic ability to drive the scission of membrane necks
GO:0180020 membrane bending activity	IDA PMID:36604498 Structural basis of CHMP2A-CHMP3 ESCRT-III polymer assembly ...	ACCEPT	Summary: Direct evidence for CHMP2A membrane bending. Reason: Core molecular function. Supporting Evidence: PMID:36604498 Epub 2023 Jan 5. Structural basis of CHMP2A-CHMP3 ESCRT-III polymer assembly and membrane cleavage.
GO:0010324 membrane invagination	IMP PMID:24878737 Structure of cellular ESCRT-III spirals and their relationsh...	ACCEPT	Summary: ESCRT-III induces membrane invagination. Reason: Core molecular function. Supporting Evidence: PMID:24878737 Structure of cellular ESCRT-III spirals and their relationship to HIV budding.
GO:0031210 phosphatidylcholine binding	IMP PMID:18687924 Helical structures of ESCRT-III are disassembled by VPS4.	ACCEPT	Summary: CHMP2A/CHMP3 polymers interact with lipid bilayers. Reason: Molecular function - ESCRT-III binds membrane lipids. Supporting Evidence: PMID:18687924 Aug 7. Helical structures of ESCRT-III are disassembled by VPS4.
GO:0051258 protein polymerization	IMP PMID:23051622 ESCRT-III CHMP2A and CHMP3 form variable helical polymers in...	ACCEPT	Summary: ESCRT-III polymerizes into helical structures. Reason: Core molecular activity. Supporting Evidence: PMID:23051622 ESCRT-III CHMP2A and CHMP3 form variable helical polymers in vitro and act synergistically during HIV-1 budding.
GO:0051258 protein polymerization	IMP PMID:24878737 Structure of cellular ESCRT-III spirals and their relationsh...	ACCEPT	Summary: ESCRT-III filament polymerization observed. Reason: Core molecular activity. Supporting Evidence: PMID:24878737 Structure of cellular ESCRT-III spirals and their relationship to HIV budding.
GO:0051260 protein homooligomerization	IMP PMID:18687924 Helical structures of ESCRT-III are disassembled by VPS4.	ACCEPT	Summary: CHMP2A can self-associate and copolymerize with CHMP3. Reason: Molecular property of ESCRT-III subunits. Supporting Evidence: PMID:18687924 Aug 7. Helical structures of ESCRT-III are disassembled by VPS4.
GO:0019904 protein domain specific binding	IPI PMID:17928862 ESCRT-III recognition by VPS4 ATPases.	ACCEPT	Summary: VPS4 recognizes CHMP2A through MIT-MIM domain interaction. Reason: Specific molecular function - CHMP2A contains MIM that binds VPS4 MIT domain. Supporting Evidence: PMID:17928862 the microtubule interacting and transport (MIT) domains of human VPS4A and VPS4B bind conserved sequence motifs located at the carboxy termini of the CHMP1-3 class of ESCRT-III proteins
GO:0019904 protein domain specific binding	IPI PMID:17928862 ESCRT-III recognition by VPS4 ATPases.	ACCEPT	Summary: VPS4B MIT domain binds CHMP2A MIM. Reason: Specific molecular function. Supporting Evidence: PMID:17928862 ESCRT-III recognition by VPS4 ATPases.
GO:1904903 ESCRT III complex disassembly	NAS PMID:20588296 Membrane budding and scission by the ESCRT machinery: it's a...	ACCEPT	Summary: VPS4-mediated ESCRT-III disassembly is required for function. Reason: Core regulatory process. Supporting Evidence: PMID:20588296 Jun 30. Membrane budding and scission by the ESCRT machinery: it's all in the neck.
GO:0005829 cytosol	TAS Reactome:R-HSA-917700	ACCEPT	Summary: CHMP2A is cytosolic in autoinhibited state before membrane recruitment. Reason: Accurate - ESCRT-III proteins exist in cytosol before activation.
GO:0005829 cytosol	TAS Reactome:R-HSA-3159232	ACCEPT	Summary: CHMP2A cytosolic localization in ESCRT pathway. Reason: Core localization when inactive.
GO:0005829 cytosol	TAS Reactome:R-HSA-5671702	ACCEPT	Summary: CHMP2A cytosolic localization. Reason: Core localization.
GO:0005829 cytosol	TAS Reactome:R-HSA-917693	ACCEPT	Summary: CHMP2A cytosolic localization. Reason: Core localization.
GO:0005829 cytosol	TAS Reactome:R-HSA-9668389	ACCEPT	Summary: CHMP2A cytosolic localization. Reason: Core localization.
GO:0005829 cytosol	TAS Reactome:R-HSA-9668395	ACCEPT	Summary: CHMP2A cytosolic localization. Reason: Core localization.
GO:0005829 cytosol	TAS Reactome:R-HSA-9668398	ACCEPT	Summary: CHMP2A cytosolic localization. Reason: Core localization.
GO:0005829 cytosol	TAS Reactome:R-HSA-9668405	ACCEPT	Summary: CHMP2A cytosolic localization. Reason: Core localization.
GO:0005829 cytosol	TAS Reactome:R-HSA-9668415	ACCEPT	Summary: CHMP2A cytosolic localization. Reason: Core localization.
GO:0005829 cytosol	TAS Reactome:R-HSA-9668419	ACCEPT	Summary: CHMP2A cytosolic localization. Reason: Core localization.
GO:0005829 cytosol	IEA GO_REF:0000107	ACCEPT	Summary: CHMP2A cytosolic localization. Reason: Core localization when inactive.
GO:0005886 plasma membrane	IDA PMID:24878737 Structure of cellular ESCRT-III spirals and their relationsh...	ACCEPT	Summary: CHMP2A localizes to plasma membrane during viral budding. Reason: Core localization for viral budding function. Supporting Evidence: PMID:24878737 Structure of cellular ESCRT-III spirals and their relationship to HIV budding.
GO:0005765 lysosomal membrane	IDA PMID:17984323 Functional multivesicular bodies are required for autophagic...	ACCEPT	Summary: CHMP2A localizes to lysosomal membrane during autophagy. Reason: ESCRT-III functions at autophagosome/MVB-lysosome interface. Supporting Evidence: PMID:17984323 Functional multivesicular bodies are required for autophagic clearance of protein aggregates associated with neurodegenerative disease.
GO:0005765 lysosomal membrane	IEA GO_REF:0000117	ACCEPT	Summary: ESCRT-III localization to lysosomal membrane. Reason: Core localization.
GO:0031902 late endosome membrane	IEA GO_REF:0000044	ACCEPT	Summary: CHMP2A localizes to late endosome/MVB membranes. Reason: Core localization.
GO:0016020 membrane	HDA PMID:19946888 Defining the membrane proteome of NK cells.	ACCEPT	Summary: CHMP2A detected in membrane proteome. Reason: General but accurate. Supporting Evidence: PMID:19946888 Defining the membrane proteome of NK cells.
GO:0030117 membrane coat	IMP PMID:24878737 Structure of cellular ESCRT-III spirals and their relationsh...	ACCEPT	Summary: ESCRT-III forms coat-like structures on membranes. Reason: ESCRT-III polymers form membrane-associated coats/spirals. Supporting Evidence: PMID:24878737 Structure of cellular ESCRT-III spirals and their relationship to HIV budding.
GO:1903543 positive regulation of exosomal secretion	IMP PMID:22660413 Syndecan-syntenin-ALIX regulates the biogenesis of exosomes.	ACCEPT	Summary: ESCRT-III involved in exosome biogenesis. Reason: Core function - MVB-derived exosomes require ESCRT. Supporting Evidence: PMID:22660413 Syntenin exosomes depend on the availability of heparan sulphate, syndecans, ALIX and ESCRTs
GO:0070062 extracellular exosome	HDA PMID:23533145 In-depth proteomic analyses of exosomes isolated from expres...	KEEP AS NON CORE	Summary: CHMP2A detected in exosome proteomics. Reason: Detection expected given ESCRT role in exosome biogenesis. Supporting Evidence: PMID:23533145 2013 Apr 23. In-depth proteomic analyses of exosomes isolated from expressed prostatic secretions in urine.
GO:0070062 extracellular exosome	HDA PMID:19056867 Large-scale proteomics and phosphoproteomics of urinary exos...	KEEP AS NON CORE	Summary: CHMP2A detected in exosome proteomics. Reason: Detection expected given ESCRT role in exosome biogenesis. Supporting Evidence: PMID:19056867 2008 Dec 3. Large-scale proteomics and phosphoproteomics of urinary exosomes.
GO:0070062 extracellular exosome	HDA PMID:20458337 MHC class II-associated proteins in B-cell exosomes and pote...	KEEP AS NON CORE	Summary: CHMP2A detected in exosome proteomics. Reason: Detection expected given ESCRT role in exosome biogenesis. Supporting Evidence: PMID:20458337 2010 May 11. MHC class II-associated proteins in B-cell exosomes and potential functional implications for exosome biogenesis.
GO:0000776 kinetochore	IDA PMID:26040712 Spastin and ESCRT-III coordinate mitotic spindle disassembly...	KEEP AS NON CORE	Summary: ESCRT-III proteins localize to kinetochores during mitosis. Reason: Non-core localization. Supporting Evidence: PMID:26040712 Spastin and ESCRT-III coordinate mitotic spindle disassembly and nuclear envelope sealing.
GO:0000776 kinetochore	IEA GO_REF:0000117	KEEP AS NON CORE	Summary: ESCRT-III localization to kinetochore. Reason: Non-core localization.
GO:0005828 kinetochore microtubule	IDA PMID:26040712 Spastin and ESCRT-III coordinate mitotic spindle disassembly...	KEEP AS NON CORE	Summary: ESCRT-III recruited to sites where NE engulfs spindle microtubules. Reason: Non-core localization. Supporting Evidence: PMID:26040712 Spastin and ESCRT-III coordinate mitotic spindle disassembly and nuclear envelope sealing.
GO:0005828 kinetochore microtubule	IEA GO_REF:0000117	KEEP AS NON CORE	Summary: ESCRT-III localization to kinetochore microtubule. Reason: Non-core localization.
GO:0005643 nuclear pore	IEA GO_REF:0000117	KEEP AS NON CORE	Summary: ESCRT-III implicated in NPC surveillance in yeast. Reason: Primary function is NE sealing rather than NPC-specific activity.
GO:0007080 mitotic metaphase chromosome alignment	IMP PMID:20616062 Human ESCRT-III and VPS4 proteins are required for centrosom...	KEEP AS NON CORE	Summary: CHMP2A depletion causes chromosome alignment defects. Reason: Secondary effect of centrosome/spindle defects. Supporting Evidence: PMID:20616062 Human ESCRT-III and VPS4 proteins are required for centrosome and spindle maintenance.
GO:0007080 mitotic metaphase chromosome alignment	IEA GO_REF:0000117	KEEP AS NON CORE	Summary: ESCRT-III role in chromosome alignment. Reason: Secondary effect.
GO:0006997 nucleus organization	IMP PMID:20616062 Human ESCRT-III and VPS4 proteins are required for centrosom...	KEEP AS NON CORE	Summary: ESCRT-III depletion causes nuclear morphology defects. Reason: Secondary effect of spindle/centrosome defects. Supporting Evidence: PMID:20616062 Human ESCRT-III and VPS4 proteins are required for centrosome and spindle maintenance.
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: CHMP2A depletion causes spindle defects. Reason: Secondary effect on spindles. Supporting Evidence: PMID:20616062 Human ESCRT-III and VPS4 proteins are required for centrosome and spindle maintenance.
GO:1901673 regulation of mitotic spindle assembly	IEA GO_REF:0000117	KEEP AS NON CORE	Summary: ESCRT-III role in spindle assembly regulation. Reason: Secondary effect.
GO:0010824 regulation of centrosome duplication	IMP PMID:20616062 Human ESCRT-III and VPS4 proteins are required for centrosom...	KEEP AS NON CORE	Summary: ESCRT-III depletion causes centrosome abnormalities. Reason: Non-core function. Supporting Evidence: PMID:20616062 Human ESCRT-III and VPS4 proteins are required for centrosome and spindle maintenance.
GO:1903723 negative regulation of centriole elongation	IMP PMID:20616062 Human ESCRT-III and VPS4 proteins are required for centrosom...	KEEP AS NON CORE	Summary: ESCRT-III may regulate centriole elongation. Reason: Indirect effect through centrosome maintenance. Supporting Evidence: PMID:20616062 Human ESCRT-III and VPS4 proteins are required for centrosome and spindle maintenance.
GO:0015031 protein transport	IBA GO_REF:0000033	ACCEPT	Summary: CHMP2A participates in protein transport through MVB-mediated sorting. Reason: Broadly accurate but general.
GO:0015031 protein transport	IEA GO_REF:0000043	ACCEPT	Summary: CHMP2A functions in protein transport. Reason: Broadly accurate.
GO:0007034 vacuolar transport	IEA GO_REF:0000002	ACCEPT	Summary: CHMP2A functions in vacuolar/lysosomal transport. Reason: Core ESCRT-III function.
GO:0051469 vesicle fusion with vacuole	NAS PMID:16505166 Recycling of ESCRTs by the AAA-ATPase Vps4 is regulated by a...	ACCEPT	Summary: ESCRT function required for MVB-lysosome fusion. Reason: Core function. Supporting Evidence: PMID:16505166 Recycling of ESCRTs by the AAA-ATPase Vps4 is regulated by a conserved VSL region in Vta1.
GO:0045184 establishment of protein localization	IMP PMID:23045692 ESCRT-III binding protein MITD1 is involved in cytokinesis a...	KEEP AS NON CORE	Summary: CHMP2A involved in protein localization through MITD1 interaction. Reason: General term - more specific functions captured elsewhere. Supporting Evidence: PMID:23045692 the MIT domain binds to a subset of ESCRT-III subunits and that this interaction mediates MITD1 recruitment to the midbody during cytokinesis
GO:0005515 protein binding	IPI PMID:16730941 A systematic analysis of human CHMP protein interactions: ad...	MARK AS OVER ANNOTATED	Summary: CHMP2A interacts with MIT domain-containing proteins. Reason: Generic - specific interaction with MITD1 or VPS4 is more informative. Supporting Evidence: PMID:16730941 two further MIT domain-containing proteins (AMSH/STAMBP and LOC129531) interact with multiple components of the human ESCRT III complex
GO:0005515 protein binding	IPI PMID:19525971 Structural basis for ESCRT-III protein autoinhibition.	MARK AS OVER ANNOTATED	Summary: CHMP2A interacts with CHMP3. Reason: Generic - specific ESCRT-III complex membership is more informative. Supporting Evidence: PMID:19525971 Jun 14. Structural basis for ESCRT-III protein autoinhibition.
GO:0005515 protein binding	IPI PMID:23051622 ESCRT-III CHMP2A and CHMP3 form variable helical polymers in...	MARK AS OVER ANNOTATED	Summary: CHMP2A interacts with CHMP4B and CHMP3. Reason: Generic - specific ESCRT-III complex membership is more informative. Supporting Evidence: PMID:23051622 ESCRT-III CHMP2A and CHMP3 form variable helical polymers in vitro and act synergistically during HIV-1 budding.
GO:0005515 protein binding	IPI PMID:25416956 A proteome-scale map of the human interactome network.	MARK AS OVER ANNOTATED	Summary: Protein interaction detected. Reason: Generic protein binding term. Supporting Evidence: PMID:25416956 A proteome-scale map of the human interactome network.
GO:0005515 protein binding	IPI PMID:26496610 A human interactome in three quantitative dimensions organiz...	MARK AS OVER ANNOTATED	Summary: Protein interaction detected. Reason: Generic protein binding term. Supporting Evidence: PMID:26496610 Oct 22. A human interactome in three quantitative dimensions organized by stoichiometries and abundances.
GO:0005515 protein binding	IPI PMID:28514442 Architecture of the human interactome defines protein commun...	MARK AS OVER ANNOTATED	Summary: Protein interaction detected. Reason: Generic protein binding term. Supporting Evidence: PMID:28514442 Architecture of the human interactome defines protein communities and disease networks.
GO:0005515 protein binding	IPI PMID:32296183 A reference map of the human binary protein interactome.	MARK AS OVER ANNOTATED	Summary: Protein interaction detected. Reason: Generic protein binding term. Supporting Evidence: PMID:32296183 Apr 8. A reference map of the human binary protein interactome.
GO:0005515 protein binding	IPI PMID:32814053 Interactome Mapping Provides a Network of Neurodegenerative ...	MARK AS OVER ANNOTATED	Summary: Protein interaction detected. Reason: Generic protein binding term. Supporting Evidence: PMID:32814053 Interactome Mapping Provides a Network of Neurodegenerative Disease Proteins and Uncovers Widespread Protein Aggregation in Affected Brains.
GO:0005515 protein binding	IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling...	MARK AS OVER ANNOTATED	Summary: Protein interaction detected. Reason: Generic protein binding term. Supporting Evidence: PMID:33961781 2021 May 6. Dual proteome-scale networks reveal cell-specific remodeling of the human interactome.
GO:0005515 protein binding	IPI PMID:35271311 OpenCell: Endogenous tagging for the cartography of human ce...	MARK AS OVER ANNOTATED	Summary: Protein interaction detected. Reason: Generic protein binding term. Supporting Evidence: PMID:35271311 2022 Mar 11. OpenCell: Endogenous tagging for the cartography of human cellular organization.
GO:0005515 protein binding	IPI PMID:18687924 Helical structures of ESCRT-III are disassembled by VPS4.	MARK AS OVER ANNOTATED	Summary: CHMP2A interacts with CHMP3 and VPS4B. Reason: Generic - specific ESCRT-III polymerization and VPS4 interaction are more informative. Supporting Evidence: PMID:18687924 Aug 7. Helical structures of ESCRT-III are disassembled by VPS4.
GO:0005515 protein binding	IPI PMID:18385515 Novel interactions of ESCRT-III with LIP5 and VPS4 and their...	MARK AS OVER ANNOTATED	Summary: Protein interaction detected. Reason: Generic protein binding term. 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...	MARK AS OVER ANNOTATED	Summary: Protein interaction detected. Reason: Generic protein binding term. Supporting Evidence: PMID:23105106 2012 Oct 26. Interactions of the human LIP5 regulatory protein with endosomal sorting complexes required for transport.
GO:0005515 protein binding	IPI PMID:14505570 The protein network of HIV budding.	MARK AS OVER ANNOTATED	Summary: CHMP2A interacts with VPS4 and other class E proteins. Reason: Generic - specific domain binding more informative. Supporting Evidence: PMID:14505570 These proteins were connected into a coherent network by 43 different protein-protein interactions
GO:0005515 protein binding	IPI PMID:14519844 Divergent retroviral late-budding domains recruit vacuolar p...	MARK AS OVER ANNOTATED	Summary: Protein interaction detected. Reason: Generic protein binding term. 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:21975012 ESCRT-III subunits Snf7-1 and Snf7-2 differentially regulate...	MARK AS OVER ANNOTATED	Summary: Protein interaction detected. Reason: Generic protein binding term. Supporting Evidence: PMID:21975012 ESCRT-III subunits Snf7-1 and Snf7-2 differentially regulate transmembrane cargos in hESC-derived human neurons.
GO:0005515 protein binding	IPI PMID:23045692 ESCRT-III binding protein MITD1 is involved in cytokinesis a...	MARK AS OVER ANNOTATED	Summary: CHMP2A interacts with MITD1. Reason: Generic - specific MIT-MIM domain interaction captured elsewhere. Supporting Evidence: PMID:23045692 ESCRT-III binding protein MITD1 is involved in cytokinesis and has an unanticipated PLD fold that binds membranes.
GO:0005515 protein binding	IPI PMID:21543490 Mechanism of inhibition of retrovirus release from cells by ...	MARK AS OVER ANNOTATED	Summary: Protein interaction detected. Reason: Generic protein binding term. Supporting Evidence: PMID:21543490 Mechanism of inhibition of retrovirus release from cells by interferon-induced gene ISG15.
GO:0005515 protein binding	IPI PMID:19129480 Essential role of hIST1 in cytokinesis.	MARK AS OVER ANNOTATED	Summary: Protein interaction detected. Reason: Generic protein binding term. Supporting Evidence: PMID:19129480 Jan 7. Essential role of hIST1 in cytokinesis.

Core Functions

CHMP2A is a core ESCRT-III subunit that copolymerizes with CHMP3 to form helical filaments on membranes, driving intraluminal vesicle formation during MVB biogenesis.

Molecular Function:

membrane bending activity

Directly Involved In:

multivesicular body sorting pathway

Cellular Locations:

multivesicular body membrane

In Complex:

ESCRT III complex

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
PMID:18687924
We found that the ESCRT-III proteins CHMP2A and CHMP3 (charged multivesicular body proteins 2A and 3) could assemble in vitro into helical tubular structures

CHMP2A forms helical filaments at the midbody that mediate membrane scission during cytokinetic abscission.

Molecular Function:

membrane bending activity

Directly Involved In:

midbody abscission

Cellular Locations:

midbody

In Complex:

ESCRT III complex

Supporting Evidence:

PMID:20616062
We found that depletion of VPS4A, VPS4B, or any of the 11 different human ESCRT-III (CHMP) proteins inhibited abscission

CHMP2A is recruited to the reforming nuclear envelope during late anaphase via the LEM2-CHMP7 pathway, sealing NE at sites where it engulfs spindle microtubules.

Molecular Function:

membrane bending activity

Directly Involved In:

nuclear membrane reassembly

Cellular Locations:

nuclear envelope

In Complex:

ESCRT III complex

Supporting Evidence:

PMID:26040712
We propose that ESCRT-III, VPS4 and spastin cooperate to coordinate nuclear envelope sealing and spindle disassembly
PMID:26040713
The ESCRT-III component charged multivesicular body protein 2A (CHMP2A) is directed to the forming NE through binding to CHMP4B, and provides an activity essential for NE reformation.

CHMP2A is hijacked by HIV-1 and other enveloped viruses for membrane scission during viral budding from the plasma membrane.

Molecular Function:

membrane bending activity

Directly Involved In:

viral budding via host ESCRT complex

Cellular Locations:

plasma membrane

In Complex:

ESCRT III complex

Supporting Evidence:

PMID:24878737
depleting Vps4 traps ESCRT-III filaments around nascent Gag assemblies

CHMP2A is required for phagophore closure to form sealed autophagosomes.

Molecular Function:

membrane bending activity

Directly Involved In:

autophagosome maturation

Cellular Locations:

autophagosome membrane

In Complex:

ESCRT III complex

Supporting Evidence:

PMID:17984323
autophagic degradation is inhibited in cells depleted of ESCRT subunits

CHMP2A is recruited within seconds to plasma membrane wounds where ESCRT machinery mediates repair via extracellular shedding of damaged membrane.

Molecular Function:

membrane bending activity

Directly Involved In:

plasma membrane repair

Cellular Locations:

plasma membrane

In Complex:

ESCRT III complex

Supporting Evidence:

PMID:24482116
ESCRT proteins were recruited within seconds to plasma membrane wounds

References

GO_REF:0000002

Gene Ontology annotation through InterPro

Annotations based on InterPro domain assignments.

GO_REF:0000033

Annotation inferred from PAINT phylogenetic analysis

Phylogenetic annotation based on PANTHER.

GO_REF:0000043

Gene Ontology annotation based on UniProt keywords

Annotations derived from UniProt keywords.

GO_REF:0000044

Gene Ontology annotation through UniProt subcellular localization

Annotations based on UniProt subcellular localization data.

GO_REF:0000107

Gene Ontology annotation by Ensembl compara

Annotations inferred from orthology.

GO_REF:0000117

ARBA annotation

Annotations based on UniProt ARBA rules.

Reactome:R-HSA-917700

Reactome pathway annotation

CHMP2A localization in ESCRT-related Reactome pathways.

PMID:14505570

The protein network of HIV budding.

CHMP2A is part of the class E protein network required for HIV-1 budding.

"dominant-negative mutants of late-acting human class E proteins arrested HIV-1 budding through plasmal and endosomal membranes"

PMID:16505166

Recycling of ESCRTs by the AAA-ATPase Vps4 is regulated by a conserved VSL region in Vta1.

Review of ESCRT machinery and Vps4-mediated recycling.

PMID:16554368

The ESCRT-III subunit hVps24 is required for degradation but not silencing of the epidermal growth factor receptor.

hVps24 depletion impairs EGFR degradation and MVB-lysosome fusion.

"Depletion of hVps24 by siRNA showed that this ESCRT subunit, like Tsg101, is important for degradation of the epidermal growth factor (EGF) receptor (EGFR)"

PMID:16730941

A systematic analysis of human CHMP protein interactions: additional MIT domain-containing proteins bind to multiple components of the human ESCRT III complex.

CHMP2A interacts with MITD1 via its MIT domain.

"two further MIT domain-containing proteins (AMSH/STAMBP and LOC129531) interact with multiple components of the human ESCRT III complex"

PMID:17928862

ESCRT-III recognition by VPS4 ATPases.

VPS4 MIT domain recognizes CHMP2A MIM element.

"the microtubule interacting and transport (MIT) domains of human VPS4A and VPS4B bind conserved sequence motifs located at the carboxy termini of the CHMP1-3 class of ESCRT-III proteins"

PMID:17984323

Functional multivesicular bodies are required for autophagic clearance of protein aggregates associated with neurodegenerative disease.

ESCRT depletion impairs autophagic degradation and causes ubiquitin-positive aggregate accumulation.

"autophagic degradation is inhibited in cells depleted of ESCRT subunits and in cells expressing CHMP2B mutants, leading to accumulation of protein aggregates containing ubiquitinated proteins"

PMID:18687924

Helical structures of ESCRT-III are disassembled by VPS4.

CHMP2A and CHMP3 copolymerize into helical tubular structures.

"We found that the ESCRT-III proteins CHMP2A and CHMP3 (charged multivesicular body proteins 2A and 3) could assemble in vitro into helical tubular structures"

PMID:19234443

Membrane scission by the ESCRT-III complex.

ESCRT-III has the intrinsic ability to drive membrane scission.

"ESCRT-III has the instrinsic ability to drive the scission of membrane necks"

PMID:19946888

Defining the membrane proteome of NK cells.

CHMP2A detected in membrane proteome.

PMID:20588296

Membrane budding and scission by the ESCRT machinery: it's all in the neck.

Review of ESCRT-III in MVB formation, viral budding, and cytokinesis.

"ESCRT-III-mediated membrane neck cleavage is crucial for many processes, including the biogenesis of multivesicular bodies, viral budding, cytokinesis, and probably autophagy"

PMID:20616062

Human ESCRT-III and VPS4 proteins are required for centrosome and spindle maintenance.

All 11 ESCRT-III proteins required for abscission; CHMP2A depletion causes monopolar spindles.

"We found that depletion of VPS4A, VPS4B, or any of the 11 different human ESCRT-III (CHMP) proteins inhibited abscission"

PMID:22660413

Syndecan-syntenin-ALIX regulates the biogenesis of exosomes.

ESCRT-III involved in exosome secretion.

"Syntenin exosomes depend on the availability of heparan sulphate, syndecans, ALIX and ESCRTs"

PMID:23045692

ESCRT-III binding protein MITD1 is involved in cytokinesis and has an unanticipated PLD fold that binds membranes.

CHMP2A involved in protein localization through MITD1.

"the MIT domain binds to a subset of ESCRT-III subunits and that this interaction mediates MITD1 recruitment to the midbody during cytokinesis"

PMID:23051622

ESCRT-III CHMP2A and CHMP3 form variable helical polymers in vitro and act synergistically during HIV-1 budding.

CHMP2A required for viral release.

"CHMP3 contributes synergistically to HIV-1 budding, and the CHMP3 contribution is ~ 10-fold more pronounced in concert with CHMP2A than with CHMP2B"

PMID:23533145

In-depth proteomic analyses of exosomes isolated from expressed prostatic secretions in urine.

CHMP2A detected in exosome proteome.

PMID:24107264

ESCRT requirements for EIAV budding.

CHMP2A-VPS4 interaction required for EIAV budding.

"EIAV budding was inhibited by point mutations that abrogate the direct interactions between ALIX:CHMP4B, CHMP4B:CHMP2A, and CHMP2A:VPS4A/B"

PMID:24482116

ESCRT machinery is required for plasma membrane repair.

ESCRT proteins recruited within seconds to plasma membrane wounds.

"ESCRT proteins were recruited within seconds to plasma membrane wounds"

PMID:24878737

Structure of cellular ESCRT-III spirals and their relationship to HIV budding.

ESCRT-III forms membrane-deforming conical spirals; VPS4 depletion traps filaments around HIV Gag.

"depleting Vps4 traps ESCRT-III filaments around nascent Gag assemblies"

PMID:26040712

Spastin and ESCRT-III coordinate mitotic spindle disassembly and nuclear envelope sealing.

ESCRT-III transiently recruited to reforming NE during late anaphase.

"We propose that ESCRT-III, VPS4 and spastin cooperate to coordinate nuclear envelope sealing and spindle disassembly"

PMID:26040713

ESCRT-III controls nuclear envelope reformation.

CHMP2A is essential for NE sealing.

"The ESCRT-III component charged multivesicular body protein 2A (CHMP2A) is directed to the forming NE through binding to CHMP4B, and provides an activity essential for NE reformation."

PMID:28242692

LEM2 recruits CHMP7 for ESCRT-mediated nuclear envelope closure in fission yeast and human cells.

CHMP2A recruitment to chromatin disks depends on LEM2-CHMP7 pathway.

PMID:36604498

Structural basis of CHMP2A-CHMP3 ESCRT-III polymer assembly and membrane cleavage.

Direct demonstration of CHMP2A membrane fission and bending activities.

file:human/CHMP2A/CHMP2A-deep-research-falcon.md

Deep research review of CHMP2A function

CHMP2A is a core ESCRT-III subunit required for phagophore closure, cytokinetic abscission, NE sealing, and viral budding.

Reactome:R-HSA-3159232

Reactome pathway - ESCRT-mediated membrane scission

CHMP2A participates in ESCRT-mediated membrane scission pathways.

Reactome:R-HSA-5671702

Reactome pathway - ESCRT-III recruitment to midbody

CHMP2A recruited to midbody for abscission.

Reactome:R-HSA-917693

Reactome pathway - Autophagic flux

CHMP2A is part of ESCRT machinery in autophagy.

Reactome:R-HSA-9668389

Reactome pathway - Nuclear envelope sealing

CHMP2A participates in nuclear envelope sealing.

Reactome:R-HSA-9668395

Reactome pathway - ESCRT complex assembly

CHMP2A is recruited to ESCRT-III complexes.

Reactome:R-HSA-9668398

Reactome pathway - Membrane scission

CHMP2A involved in ESCRT-mediated membrane scission.

Reactome:R-HSA-9668405

Reactome pathway - MVB formation

CHMP2A participates in MVB biogenesis.

Reactome:R-HSA-9668415

Reactome pathway - Viral budding

CHMP2A hijacked by viruses for budding.

Reactome:R-HSA-9668419

Reactome pathway - Plasma membrane repair

CHMP2A involved in plasma membrane wound repair.

PMID:19056867

Large-scale proteomics and phosphoproteomics of urinary exosomes.

CHMP2A detected in exosome proteome.

PMID:20458337

MHC class II-associated proteins in B-cell exosomes and potential functional implications for exosome biogenesis.

CHMP2A detected in exosome proteome.

PMID:19525971

Structural basis for ESCRT-III protein autoinhibition.

CHMP2A interacts with CHMP3 in ESCRT-III complex.

PMID:25416956

A proteome-scale map of the human interactome network.

Protein-protein interaction detected.

PMID:26496610

A human interactome in three quantitative dimensions organized by stoichiometries and abundances.

Protein-protein interaction detected.

PMID:28514442

Architecture of the human interactome defines protein communities and disease networks.

Protein-protein interaction detected.

PMID:32296183

A reference map of the human binary protein interactome.

Protein-protein interaction detected.

PMID:32814053

Interactome Mapping Provides a Network of Neurodegenerative Disease Proteins and Uncovers Widespread Protein Aggregation in Affected Brains.

Protein-protein interaction detected.

PMID:33961781

Dual proteome-scale networks reveal cell-specific remodeling of the human interactome.

Protein-protein interaction detected.

PMID:35271311

OpenCell: Endogenous tagging for the cartography of human cellular organization.

Protein-protein interaction detected.

PMID:18385515

Novel interactions of ESCRT-III with LIP5 and VPS4 and their implications for ESCRT-III disassembly.

CHMP2A interacts with ESCRT-III related proteins.

PMID:23105106

Interactions of the human LIP5 regulatory protein with endosomal sorting complexes required for transport.

CHMP2A interacts with ESCRT-III related proteins.

PMID:14519844

Divergent retroviral late-budding domains recruit vacuolar protein sorting factors by using alternative adaptor proteins.

CHMP2A interacts with class E proteins.

PMID:21975012

ESCRT-III subunits Snf7-1 and Snf7-2 differentially regulate transmembrane cargos in hESC-derived human neurons.

Protein-protein interaction detected.

PMID:21543490

Mechanism of inhibition of retrovirus release from cells by interferon-induced gene ISG15.

Protein-protein interaction detected.

PMID:19129480

Essential role of hIST1 in cytokinesis.

Protein-protein interaction detected.

Deep Research

Falcon

(CHMP2A-deep-research-falcon.md)

this with annotations you find in gene/protein databases, but these can be outdated or inaccurate. Falcon Edison Scientific Literature 21 citations 2025-12-27T23:21:36.185963

The research report should be a detailed narrative explaining the function, biological processes, and localization of the gene product. Citations should be given for all claims.

You should prioritize authoritative reviews and primary scientific literature when conducting research. You can supplement
this with annotations you find in gene/protein databases, but these can be outdated or inaccurate.

We are specifically interested in the primary function of the gene - for enzymes, what reaction is catalyzed, and what is the substrate specificity? For transporters, what is the substrate? For structural proteins or adapters, what is the broader structural role? For signaling molecules, what is the role in the pathway.

We are interested in where in or outside the cell the gene product carries out its function.

We are also interested in the signaling or biochemical pathways in which the gene functions. We are less interested in broad pleiotropic effects, except where these elucidate the precise role.

Include evidence where possible. We are interested in both experimental evidence as well as inference from structure, evolution, or bioinformatic analysis. Precise studies should be prioritized over high-throughput, where available.

Plan overview
- We verified gene/protein identity (CHMP2A, UniProt O43633) and then gathered recent primary and review literature on ESCRT-III, with emphasis on 2023–2024 sources, to synthesize function, mechanism, partners, localization, regulation, disease links, and applications. Key quantitative and mechanistic findings were extracted where available (noting that CHMP2A-specific effect sizes are rarely reported).

1) Key concepts and definitions with current understanding
- Identity and family: CHMP2A (Charged multivesicular body protein 2A) is a human ESCRT‑III subunit in the SNF7 family with a conserved α‑helical hairpin fold that polymerizes on membranes to mediate reverse‑topology membrane constriction and scission. Like other ESCRT‑III proteins, subunits are autoinhibited in the cytosol and are recycled by the AAA+ ATPases VPS4A/B after polymerization (threading/unfolding) (review synthesis) (park2024escrtiiiaversatile pages 1-2, hurley2025theexpandingrepertoire pages 1-2, hurley2025theexpandingrepertoire pages 8-9).
- Primary biochemical role: ESCRT‑III—including CHMP2A—assembles into spirals/helices on membranes; VPS4 drives dynamic turnover and scission, enabling intraluminal vesicle (ILV) formation, viral budding, cytokinetic abscission, autophagosome/phagophore closure, nuclear envelope sealing, and membrane/lysosome repair (reviews) (park2024escrtiiiaversatile pages 1-2, park2024escrtiiiaversatile pages 13-14, park2024escrtiiiaversatile pages 7-8, hurley2025theexpandingrepertoire pages 1-2, hurley2025theexpandingrepertoire pages 8-9).
- Specific role in autophagy: CHMP2A is required for phagophore closure to generate sealed double‑membrane autophagosomes. Depletion leads to accumulation of unclosed autophagic membranes and impaired autophagic flux; dominant‑negative VPS4 phenocopies this, consistent with ESCRT‑III/VPS4‑dependent membrane abscission at the phagophore edge (primary) (takahashi2018anautophagyassay pages 6-7, hattori2021targetingtheescrtiii pages 1-2, park2024escrtiiiaversatile pages 1-2, park2024escrtiiiaversatile pages 7-8).

2) Mechanism, structure and partners
- Polymerization and architecture: ESCRT‑III subunits (including CHMP paralogs) assemble into flat spirals and helical collars on membranes as primed states that transition during constriction. Structural work and reviews show ESCRT‑III polymers cause bilayer thinning and curvature; the N‑terminal amphipathic/membrane‑facing helices and basic residues contact acidic lipids (e.g., PIP2) (2023–2024) (moss2023brominatedlipidprobes pages 7-8, hurley2025theexpandingrepertoire pages 8-9, park2024escrtiiiaversatile pages 1-2). Although CHMP1B/IST1 were the model in the cryo‑EM lipid studies, the principles of ESCRT‑III helix–lipid interactions and constriction apply to CHMP2A polymers (review integration) (moss2023brominatedlipidprobes pages 7-8, park2024escrtiiiaversatile pages 1-2, hurley2025theexpandingrepertoire pages 8-9).
- Assembly order and turnover: ESCRT‑III recruitment often proceeds from ESCRT‑0/I/II and/or ALIX (PDCD6IP), then polymerization of CHMPs including CHMP4B, CHMP2A/CHMP3, etc., followed by VPS4‑driven disassembly to power scission (reviews). ALIX and TSG101 are adaptors at several sites (midbody, viral buds), and CHMP7 can nucleate nuclear envelope recruitment (reviews) (park2024escrtiiiaversatile pages 1-2, park2024escrtiiiaversatile pages 13-14, park2024escrtiiiaversatile pages 7-8).
- Key partners for CHMP2A function: CHMP3 (forms copolymers with CHMP2A), CHMP4B (initiator scaffold), ALIX/PDCD6IP (adaptor), VPS4A/B (disassembly ATPases), ESCRT‑II component VPS36 (via Arl4A, affecting CHMP2A’s ability to recruit USP8), and upstream ESCRT‑I/II (TSG101, VPS36). 2023 work shows endosomal Arl4A stabilizes VPS36–ESCRT‑III association and delays EGFR degradation by attenuating CHMP2A‑mediated USP8 recruitment in endosomal sorting (primary) ().

3) Cellular/localization context and pathways
- Sites of action: CHMP2A localizes to phagophores and autophagosomal membranes during autophagy; signals are adjacent to LC3‑positive structures and increase with starvation (primary). VPS4 inhibition causes accumulation of immature, unsealed autophagic membranes, consistent with ESCRT‑III at the phagophore neck (primary) (takahashi2018anautophagyassay pages 6-7, hattori2021targetingtheescrtiii pages 1-2).
- Endosome/MVB and signaling receptors: In the EGFR pathway, Arl4A–VPS36 association modulates ESCRT‑III function, affecting CHMP2A‑dependent USP8 recruitment and EGFR ubiquitin clearance/degradation, linking CHMP2A to receptor downregulation tempo (primary) ().
- Cytokinetic abscission and genome integrity: ESCRT‑III (including CHMP2A) forms cortical rings/spirals at the midbody to execute abscission. Reviews in 2024 summarize CHMP2A/CHMP4B/IST1 at the midbody and their role in the abscission checkpoint and genome integrity protection (reviews) (park2024escrtiiiaversatile pages 13-14).
- Nuclear envelope repair/reformation: ESCRT‑III is recruited to nuclear envelope gaps/ruptures to restore compartmentalization; CHMP7 helps nucleate ESCRT‑III at the inner nuclear membrane, with CHMP2A among recruited ESCRT‑III subunits (reviews) (park2024escrtiiiaversatile pages 7-8, park2024escrtiiiaversatile pages 13-14).

4) Regulation (post‑translational, lipid, dynamics)
- Autoinhibition and activation: CHMP proteins’ C‑termini autoinhibit polymerization; membrane binding and activation expose interfaces for filament assembly; VPS4 recycles subunits via MIT‑MIM interactions (review consensus) (park2024escrtiiiaversatile pages 1-2, hurley2025theexpandingrepertoire pages 1-2).
- Lipid dependence: ESCRT‑III constriction is stabilized by interactions with acidic phospholipids (e.g., PIP2) and by creation of local hydrophobic defects where polyunsaturated acyl chains accumulate at the outer leaflet surface; these features slow lipid diffusion in constricted tubules and support scission mechanics (2023 cryo‑EM + MD) (moss2023brominatedlipidprobes pages 7-8).
- Cross‑pathway regulation: At endosomes, Arl4A binding to ESCRT‑II (VPS36) perturbs ESCRT‑III progression and CHMP2A‑dependent USP8 recruitment, linking small GTPases to ESCRT timing and deubiquitinase access (2023) (). Additional post‑translational regulation of ESCRT‑III is recognized broadly (e.g., methylation of CHMP2B at abscission), underscoring analogous regulatory logic across paralogs (review context) (park2024escrtiiiaversatile pages 1-2).

5) Disease links, applications, expert views, and data
- Neurodegeneration and membrane repair/autophagy failure: ESCRT‑III dysfunction contributes to autophagy and membrane repair defects implicated in neurodegenerative disease. Recent reviews emphasize ESCRT‑III roles in nuclear surveillance and endolysosomal trafficking in the CNS; altered ESCRT‑III function is linked to FTD/ALS and AD pathogenesis. While much genotype–disease data centers on CHMP2B, CHMP2A is included among ESCRT‑III factors required for autophagosome completion in neurons, and its depletion causes accumulation of unsealed autophagosomes and perturbs proteostasis (reviews, primary) (park2024escrtiiiaversatile pages 7-8, park2024escrtiiiaversatile pages 1-2, takahashi2018anautophagyassay pages 6-7, hattori2021targetingtheescrtiii pages 1-2).
- Autophagy–cell death crosstalk and oncology: CHMP2A loss stabilizes iDISCs on immature autophagosomal membranes and triggers noncanonical Caspase‑8 activation and apoptosis, connecting ESCRT‑III closure failure to death signaling. In vivo, CHMP2A depletion impaired neuroblastoma tumor growth while increasing apoptosis, suggesting context‑dependent therapeutic leverage of ESCRT‑III–autophagy interfaces (primary) (hattori2021targetingtheescrtiii pages 1-2).
- Receptor signaling and cancer relevance: By attenuating CHMP2A‑dependent USP8 recruitment, Arl4A–VPS36 slows EGFR deubiquitylation turnover and degradation, potentially prolonging signaling; given EGFR’s centrality in many malignancies, this places CHMP2A within an actionable endosomal sorting axis (primary, 2023) ().
- Expert consensus and translational notes: Contemporary reviews (2024–2025) underscore ESCRT‑III’s broad disease impact—from infections and immune disorders to cancer and neurological disease—and discuss targeting ESCRT adaptors or the disassembly ATPase VPS4 in specific contexts; ESCRT-III subunits themselves are scaffolds without catalytic activity, making direct small‑molecule targeting challenging (reviews) (park2024escrtiiiaversatile pages 1-2, hurley2025theexpandingrepertoire pages 1-2, hurley2025theexpandingrepertoire pages 8-9).

6) Quantitative/statistical data where available
- Autophagosome closure assays (human cells) showed significant accumulation of unsealed autophagic membranes upon CHMP2A depletion; experiments typically quantified ≥50 cells per group with strong significance (e.g., **** p ≤ 0.0001), and dominant‑negative VPS4A (E228Q) phenocopied closure defects under basal and starved conditions (primary) (takahashi2018anautophagyassay pages 6-7).
- CHMP2A depletion in the Caspase‑8/iDISC study increased LC3‑II and p62 levels and activated Caspase‑8; genetic epistasis showed ATG7 deletion prevented Caspase‑8 activation after CHMP2A loss, supporting a mechanistic linkage (primary). In vivo, CHMP2A knockdown reduced neuroblastoma tumor growth (quantitative tumor growth curves reported in the paper) (hattori2021targetingtheescrtiii pages 1-2).
- Structural/biophysical: ESCRT‑III constriction remodels leaflet organization and slows lipid diffusion in outer leaflets of constricted tubules; cryo‑EM with brominated lipids revealed protein‑localized lipid asymmetries and defects enabling accumulation of polyunsaturated tails in the outer leaflet (2023) (moss2023brominatedlipidprobes pages 7-8).

7) Current applications and real‑world implementations (2023–2024 highlights)
- Mechanistic reconstitution and structural advances continue to refine ESCRT‑III models of scission that inform antiviral and anticancer strategies where ESCRT is hijacked or rate‑limiting (reviews) (park2024escrtiiiaversatile pages 1-2, hurley2025theexpandingrepertoire pages 8-9).
- Endosomal EGFR sorting modulation via Arl4A–VPS36–CHMP2A/USP8 provides a concrete regulatory node with implications for tuning receptor downregulation kinetics in cancer models (primary, 2023) ().
- Neurodegeneration: Expert reviews in 2024 emphasize ESCRT‑III’s roles in neuronal nuclear envelope integrity and endolysosomal trafficking, informing therapeutic hypotheses that aim to bolster ESCRT‑mediated repair and autophagy completion (reviews) (park2024escrtiiiaversatile pages 7-8).

8) Verification checklist (per request)
- Symbol and description match: CHMP2A matches “Charged multivesicular body protein 2a,” human ESCRT‑III. Literature consistently places CHMP2A in ESCRT‑III/SNF7 family (reviews) (park2024escrtiiiaversatile pages 1-2, hurley2025theexpandingrepertoire pages 1-2).
- Organism: Homo sapiens, as in all cited primary human‑cell studies (e.g., Takahashi 2018; Lin 2023) (takahashi2018anautophagyassay pages 6-7).
- Domains/family: SNF7/ESCRT‑III fold and dynamics align with reviews and structural studies (park2024escrtiiiaversatile pages 1-2, hurley2025theexpandingrepertoire pages 8-9, moss2023brominatedlipidprobes pages 7-8).
- Ambiguity: No conflicting gene symbol usage detected in the cited 2023–2024 literature; CHMP2A is distinct from CHMP2B (noted explicitly where assays discriminate them) (takahashi2018anautophagyassay pages 6-7, park2024escrtiiiaversatile pages 1-2).

References with URLs and dates
- Park J et al. ESCRT‑III: a versatile membrane remodeling machinery and its implications in cellular processes and diseases. Animal Cells and Systems. 2024 Jul;28:367–380. DOI: 10.1080/19768354.2024.2380294. URL: https://doi.org/10.1080/19768354.2024.2380294 (park2024escrtiiiaversatile pages 1-2, park2024escrtiiiaversatile pages 7-8, park2024escrtiiiaversatile pages 13-14).
- Takahashi Y et al. An autophagy assay reveals the ESCRT‑III component CHMP2A as a regulator of phagophore closure. Nat Commun. 2018 Jul. DOI: 10.1038/s41467-018-05254-w. URL: https://doi.org/10.1038/s41467-018-05254-w (takahashi2018anautophagyassay pages 6-7).
- Hattori T et al. Targeting the ESCRT‑III component CHMP2A for noncanonical Caspase‑8 activation on autophagosomal membranes. Cell Death & Differ. 2021 Aug;28:657–670. DOI: 10.1038/s41418-020-00610-0. URL: https://doi.org/10.1038/s41418-020-00610-0 (hattori2021targetingtheescrtiii pages 1-2).
- Lin S‑J et al. Endosomal Arl4A attenuates EGFR degradation by binding to the ESCRT‑II component VPS36. Nat Commun. 2023 Nov;14(1). DOI: 10.1038/s41467-023-42979-9. URL: https://doi.org/10.1038/s41467-023-42979-9 ().
- Moss FR et al. Brominated lipid probes expose structural asymmetries in constricted membranes. Nat Struct Mol Biol. 2023 Jan;30:167–175. DOI: 10.1038/s41594-022-00898-1. URL: https://doi.org/10.1038/s41594-022-00898-1 (moss2023brominatedlipidprobes pages 7-8).
- La Torre M et al. Preserving Genome Integrity: Unveiling the Roles of ESCRT Machinery. Cells. 2024 Aug;13(15):1307. DOI: 10.3390/cells13151307. URL: https://doi.org/10.3390/cells13151307 ().
- Keeley O, Coyne AN. Nuclear and degradative functions of the ESCRT‑III pathway: implications for neurodegenerative disease. Nucleus. 2024 May;15(1). DOI: 10.1080/19491034.2024.2349085. URL: https://doi.org/10.1080/19491034.2024.2349085 (park2024escrtiiiaversatile pages 7-8).
- Hurley JH et al. The expanding repertoire of ESCRT functions in cell biology and disease. Nature. 2025 Jun;642:877–888. DOI: 10.1038/s41586-025-08950-y. URL: https://doi.org/10.1038/s41586-025-08950-y (overarching expert review). While 2025, it provides authoritative mechanistic synthesis relevant to CHMP2A (hurley2025theexpandingrepertoire pages 1-2, hurley2025theexpandingrepertoire pages 8-9).

Conclusion
- CHMP2A is a bona fide human ESCRT‑III/SNF7‑family subunit that copolymerizes with CHMP3 and functions with CHMP4B, ALIX, and VPS4 to execute membrane scission across endosomal sorting, autophagosome closure, cytokinetic abscission, and nuclear envelope repair. Its role in phagophore closure is supported by direct human‑cell experiments; its regulatory and disease connections (EGFR trafficking, neurodegeneration‑relevant autophagy and membrane repair) are reinforced by 2023–2024 primary and review literature. ESCRT‑III’s structural principles (polymerization into spirals/helices, lipid engagement, VPS4‑driven turnover) underpin CHMP2A’s functional annotation and suggest translational nodes (e.g., endosomal sorting modulation, ESCRT‑VPS4 axis) (takahashi2018anautophagyassay pages 6-7, hattori2021targetingtheescrtiii pages 1-2, park2024escrtiiiaversatile pages 1-2, park2024escrtiiiaversatile pages 13-14, park2024escrtiiiaversatile pages 7-8, moss2023brominatedlipidprobes pages 7-8, hurley2025theexpandingrepertoire pages 1-2).

References

(park2024escrtiiiaversatile pages 1-2): Jisoo Park, Jongyoon Kim, Hyungsun Park, Taewan Kim, and Seongju Lee. Escrt-iii: a versatile membrane remodeling machinery and its implications in cellular processes and diseases. Animal Cells and Systems, 28:367-380, Jul 2024. URL: https://doi.org/10.1080/19768354.2024.2380294, doi:10.1080/19768354.2024.2380294. This article has 11 citations and is from a peer-reviewed journal.
(hurley2025theexpandingrepertoire pages 1-2): James H. Hurley, Alyssa N. Coyne, Marta Miączyńska, and Harald Stenmark. The expanding repertoire of escrt functions in cell biology and disease. Nature, 642:877-888, Jun 2025. URL: https://doi.org/10.1038/s41586-025-08950-y, doi:10.1038/s41586-025-08950-y. This article has 13 citations and is from a highest quality peer-reviewed journal.
(hurley2025theexpandingrepertoire pages 8-9): James H. Hurley, Alyssa N. Coyne, Marta Miączyńska, and Harald Stenmark. The expanding repertoire of escrt functions in cell biology and disease. Nature, 642:877-888, Jun 2025. URL: https://doi.org/10.1038/s41586-025-08950-y, doi:10.1038/s41586-025-08950-y. This article has 13 citations and is from a highest quality peer-reviewed journal.
(park2024escrtiiiaversatile pages 13-14): Jisoo Park, Jongyoon Kim, Hyungsun Park, Taewan Kim, and Seongju Lee. Escrt-iii: a versatile membrane remodeling machinery and its implications in cellular processes and diseases. Animal Cells and Systems, 28:367-380, Jul 2024. URL: https://doi.org/10.1080/19768354.2024.2380294, doi:10.1080/19768354.2024.2380294. This article has 11 citations and is from a peer-reviewed journal.
(park2024escrtiiiaversatile pages 7-8): Jisoo Park, Jongyoon Kim, Hyungsun Park, Taewan Kim, and Seongju Lee. Escrt-iii: a versatile membrane remodeling machinery and its implications in cellular processes and diseases. Animal Cells and Systems, 28:367-380, Jul 2024. URL: https://doi.org/10.1080/19768354.2024.2380294, doi:10.1080/19768354.2024.2380294. This article has 11 citations and is from a peer-reviewed journal.
(takahashi2018anautophagyassay pages 6-7): Yoshinori Takahashi, Haiyan He, Zhenyuan Tang, Tatsuya Hattori, Ying Liu, Megan M. Young, Jacob M. Serfass, Longgui Chen, Melat Gebru, Chong Chen, Carson A. Wills, Jennifer M. Atkinson, Han Chen, Thomas Abraham, and Hong-Gang Wang. An autophagy assay reveals the escrt-iii component chmp2a as a regulator of phagophore closure. Nature Communications, Jul 2018. URL: https://doi.org/10.1038/s41467-018-05254-w, doi:10.1038/s41467-018-05254-w. This article has 413 citations and is from a highest quality peer-reviewed journal.
(hattori2021targetingtheescrtiii pages 1-2): Tatsuya Hattori, Yoshinori Takahashi, Longgui Chen, Zhenyuan Tang, Carson A. Wills, Xinwen Liang, and Hong-Gang Wang. Targeting the escrt-iii component chmp2a for noncanonical caspase-8 activation on autophagosomal membranes. Cell Death & Differentiation, 28:657-670, Aug 2021. URL: https://doi.org/10.1038/s41418-020-00610-0, doi:10.1038/s41418-020-00610-0. This article has 24 citations and is from a domain leading peer-reviewed journal.
(moss2023brominatedlipidprobes pages 7-8): Frank R. Moss, James Lincoff, Maxwell Tucker, Arshad Mohammed, Michael Grabe, and Adam Frost. Brominated lipid probes expose structural asymmetries in constricted membranes. Nature Structural & Molecular Biology, 30:167-175, Jan 2023. URL: https://doi.org/10.1038/s41594-022-00898-1, doi:10.1038/s41594-022-00898-1. This article has 33 citations and is from a highest quality peer-reviewed journal.

Citations

park2024escrtiiiaversatile pages 13-14
moss2023brominatedlipidprobes pages 7-8
park2024escrtiiiaversatile pages 1-2
hattori2021targetingtheescrtiii pages 1-2
takahashi2018anautophagyassay pages 6-7
park2024escrtiiiaversatile pages 7-8
hurley2025theexpandingrepertoire pages 1-2
hurley2025theexpandingrepertoire pages 8-9
https://doi.org/10.1080/19768354.2024.2380294
https://doi.org/10.1038/s41467-018-05254-w
https://doi.org/10.1038/s41418-020-00610-0
https://doi.org/10.1038/s41467-023-42979-9
https://doi.org/10.1038/s41594-022-00898-1
https://doi.org/10.3390/cells13151307
https://doi.org/10.1080/19491034.2024.2349085
https://doi.org/10.1038/s41586-025-08950-y
https://doi.org/10.1080/19768354.2024.2380294,
https://doi.org/10.1038/s41586-025-08950-y,
https://doi.org/10.1038/s41467-018-05254-w,
https://doi.org/10.1038/s41418-020-00610-0,
https://doi.org/10.1038/s41594-022-00898-1,

📄 View Raw YAML

id: O43633
gene_symbol: CHMP2A
product_type: PROTEIN
status: COMPLETE
taxon:
  id: NCBITaxon:9606
  label: Homo sapiens
description: >-
  CHMP2A is a core ESCRT-III subunit that functions in membrane scission events with
  reverse topology. Key roles include MVB biogenesis, cytokinetic abscission, nuclear
  envelope reformation, viral budding, autophagosome closure, and plasma membrane
  repair.

existing_annotations:
# ESCRT III complex - IBA
- term:
    id: GO:0000815
    label: ESCRT III complex
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    summary: CHMP2A is a core ESCRT-III subunit that copolymerizes with CHMP3.
    action: ACCEPT
    reason: Definitional - CHMP2A is a bona fide ESCRT-III subunit (PMID:18687924).
    supported_by:
    - reference_id: PMID:18687924
      supporting_text: "We found that the ESCRT-III proteins CHMP2A and CHMP3 (charged\
        \ multivesicular body proteins 2A and 3) could assemble in vitro into helical\
        \ tubular structures"

# ESCRT III complex - IDA (PMID:18687924)
    - reference_id: file:human/CHMP2A/CHMP2A-deep-research-falcon.md
      supporting_text: 'model: Edison Scientific Literature'
- term:
    id: GO:0000815
    label: ESCRT III complex
  evidence_type: IDA
  original_reference_id: PMID:18687924
  review:
    summary: Direct evidence for CHMP2A-CHMP3 copolymerization.
    action: ACCEPT
    reason: Core function confirmed by structural studies.

# ESCRT III complex - IDA (PMID:26040712)
    supported_by:
    - reference_id: PMID:18687924
      supporting_text: Aug 7. Helical structures of ESCRT-III are disassembled by
        VPS4.
- term:
    id: GO:0000815
    label: ESCRT III complex
  evidence_type: IDA
  original_reference_id: PMID:26040712
  review:
    summary: ESCRT-III localization confirmed during NE sealing.
    action: ACCEPT
    reason: Core function confirmed.

# ESCRT III complex - TAS
    supported_by:
    - reference_id: PMID:26040712
      supporting_text: Spastin and ESCRT-III coordinate mitotic spindle disassembly
        and nuclear envelope sealing.
- term:
    id: GO:0000815
    label: ESCRT III complex
  evidence_type: TAS
  original_reference_id: PMID:20588296
  review:
    summary: ESCRT-III role in membrane scission reviewed.
    action: ACCEPT
    reason: Core complex membership.

# multivesicular body - IBA
    supported_by:
    - reference_id: PMID:20588296
      supporting_text: "Jun 30. Membrane budding and scission by the ESCRT machinery:\
        \ it's all in the neck."
- term:
    id: GO:0005771
    label: multivesicular body
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    summary: CHMP2A localizes to MVB membranes during ILV formation.
    action: ACCEPT
    reason: Core localization supported by literature (PMID:16554368).

# multivesicular body membrane - IDA
- term:
    id: GO:0032585
    label: multivesicular body membrane
  evidence_type: IDA
  original_reference_id: PMID:16554368
  review:
    summary: ESCRT-III localizes to MVB membranes.
    action: ACCEPT
    reason: Core localization - endogenous hVps24 localized to late endosomes.

# multivesicular body membrane - IEA
    supported_by:
    - reference_id: PMID:16554368
      supporting_text: Mar 22. The ESCRT-III subunit hVps24 is required for degradation
        but not silencing of the epidermal growth factor receptor.
- term:
    id: GO:0032585
    label: multivesicular body membrane
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  review:
    summary: ESCRT-III localization to MVB membrane.
    action: ACCEPT
    reason: Consistent with core function.

# multivesicular body sorting pathway - IDA
- term:
    id: GO:0071985
    label: multivesicular body sorting pathway
  evidence_type: IDA
  original_reference_id: PMID:16554368
  review:
    summary: CHMP2A functions in MVB sorting.
    action: ACCEPT
    reason: Core function - hVps24 depletion impairs EGFR degradation.

# multivesicular body sorting pathway - IEA
    supported_by:
    - reference_id: PMID:16554368
      supporting_text: Mar 22. The ESCRT-III subunit hVps24 is required for degradation
        but not silencing of the epidermal growth factor receptor.
- term:
    id: GO:0071985
    label: multivesicular body sorting pathway
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  review:
    summary: ESCRT-III required for MVB sorting.
    action: ACCEPT
    reason: Core function.

# endosome transport via multivesicular body sorting pathway - IBA
- term:
    id: GO:0032509
    label: endosome transport via multivesicular body sorting pathway
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    summary: CHMP2A required for MVB-mediated transport.
    action: ACCEPT
    reason: Core function of ESCRT-III.

# ubiquitin-dependent protein catabolic process via MVB - IDA
- term:
    id: GO:0043162
    label: ubiquitin-dependent protein catabolic process via the multivesicular body
      sorting pathway
  evidence_type: IDA
  original_reference_id: PMID:17984323
  review:
    summary: ESCRT-III sorts ubiquitinated cargo for degradation.
    action: ACCEPT
    reason: Core function.

# ubiquitin-dependent protein catabolic process via MVB - IEA
    supported_by:
    - reference_id: PMID:17984323
      supporting_text: Functional multivesicular bodies are required for autophagic
        clearance of protein aggregates associated with neurodegenerative disease.
- term:
    id: GO:0043162
    label: ubiquitin-dependent protein catabolic process via the multivesicular body
      sorting pathway
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  review:
    summary: ESCRT-III required for ubiquitinated cargo degradation.
    action: ACCEPT
    reason: Core function.

# multivesicular body assembly - TAS
- term:
    id: GO:0036258
    label: multivesicular body assembly
  evidence_type: TAS
  original_reference_id: PMID:20588296
  review:
    summary: ESCRT-III is required for MVB assembly.
    action: ACCEPT
    reason: Core function.

# multivesicular body assembly - NAS
    supported_by:
    - reference_id: PMID:20588296
      supporting_text: "Jun 30. Membrane budding and scission by the ESCRT machinery:\
        \ it's all in the neck."
- term:
    id: GO:0036258
    label: multivesicular body assembly
  evidence_type: NAS
  original_reference_id: PMID:16505166
  review:
    summary: ESCRT function required for MVB assembly.
    action: ACCEPT
    reason: Core function.

# late endosome to vacuole transport - IBA
    supported_by:
    - reference_id: PMID:16505166
      supporting_text: Recycling of ESCRTs by the AAA-ATPase Vps4 is regulated by
        a conserved VSL region in Vta1.
- term:
    id: GO:0045324
    label: late endosome to vacuole transport
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    summary: CHMP2A functions in late endosome maturation.
    action: ACCEPT
    reason: ESCRT-III required for MVE-lysosome fusion (PMID:16554368).

# late endosome to lysosome transport - IMP
- term:
    id: GO:1902774
    label: late endosome to lysosome transport
  evidence_type: IMP
  original_reference_id: PMID:17984323
  review:
    summary: ESCRT-III required for late endosome to lysosome transport.
    action: ACCEPT
    reason: Core function.

# late endosome to lysosome transport - IEA
    supported_by:
    - reference_id: PMID:17984323
      supporting_text: Functional multivesicular bodies are required for autophagic
        clearance of protein aggregates associated with neurodegenerative disease.
- term:
    id: GO:1902774
    label: late endosome to lysosome transport
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  review:
    summary: ESCRT-III required for late endosome to lysosome transport.
    action: ACCEPT
    reason: Core function.

# multivesicular body-lysosome fusion - NAS
- term:
    id: GO:0061763
    label: multivesicular body-lysosome fusion
  evidence_type: NAS
  original_reference_id: PMID:16505166
  review:
    summary: ESCRT function required for MVB-lysosome fusion.
    action: ACCEPT
    reason: Core function.

# midbody abscission - IMP (PMID:20616062)
    supported_by:
    - reference_id: PMID:16505166
      supporting_text: Recycling of ESCRTs by the AAA-ATPase Vps4 is regulated by
        a conserved VSL region in Vta1.
- term:
    id: GO:0061952
    label: midbody abscission
  evidence_type: IMP
  original_reference_id: PMID:20616062
  review:
    summary: CHMP2A required for cytokinetic abscission.
    action: ACCEPT
    reason: Core function - ESCRT-III depletion inhibits abscission.
    supported_by:
    - reference_id: PMID:20616062
      supporting_text: "We found that depletion of VPS4A, VPS4B, or any of the 11\
        \ different human ESCRT-III (CHMP) proteins inhibited abscission"

# midbody abscission - IEA
- term:
    id: GO:0061952
    label: midbody abscission
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  review:
    summary: CHMP2A required for cytokinetic abscission.
    action: ACCEPT
    reason: Core function.

# midbody - IDA
- term:
    id: GO:0030496
    label: midbody
  evidence_type: IDA
  original_reference_id: PMID:26040712
  review:
    summary: ESCRT-III localizes to midbody during cytokinesis.
    action: ACCEPT
    reason: Core localization for abscission function.

# midbody - IEA
    supported_by:
    - reference_id: PMID:26040712
      supporting_text: Spastin and ESCRT-III coordinate mitotic spindle disassembly
        and nuclear envelope sealing.
- term:
    id: GO:0030496
    label: midbody
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  review:
    summary: ESCRT-III localizes to midbody.
    action: ACCEPT
    reason: Core localization.

# nuclear membrane reassembly - IMP (PMID:26040712)
- term:
    id: GO:0031468
    label: nuclear membrane reassembly
  evidence_type: IMP
  original_reference_id: PMID:26040712
  review:
    summary: ESCRT-III required for NE sealing during mitotic exit.
    action: ACCEPT
    reason: Core function.
    supported_by:
    - reference_id: PMID:26040712
      supporting_text: "We propose that ESCRT-III, VPS4 and spastin cooperate to coordinate\
        \ nuclear envelope sealing and spindle disassembly"

# nuclear membrane reassembly - IMP (PMID:26040713)
- term:
    id: GO:0031468
    label: nuclear membrane reassembly
  evidence_type: IMP
  original_reference_id: PMID:26040713
  review:
    summary: ESCRT-III required for NE sealing.
    action: ACCEPT
    reason: Core function.
    supported_by:
    - reference_id: PMID:26040713
      supporting_text: "The ESCRT-III component charged multivesicular body protein\
        \ 2A (CHMP2A) is directed to the forming NE through binding to CHMP4B, and\
        \ provides an activity essential for NE reformation."

# nuclear membrane reassembly - IEA
- term:
    id: GO:0031468
    label: nuclear membrane reassembly
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  review:
    summary: ESCRT-III required for nuclear membrane reassembly.
    action: ACCEPT
    reason: Core function.

# nuclear envelope - IDA
- term:
    id: GO:0005635
    label: nuclear envelope
  evidence_type: IDA
  original_reference_id: PMID:26040712
  review:
    summary: ESCRT-III localizes to nuclear envelope during reformation.
    action: ACCEPT
    reason: Core localization for NE sealing.

# nuclear envelope - IEA
    supported_by:
    - reference_id: PMID:26040712
      supporting_text: Spastin and ESCRT-III coordinate mitotic spindle disassembly
        and nuclear envelope sealing.
- term:
    id: GO:0005635
    label: nuclear envelope
  evidence_type: IEA
  original_reference_id: GO_REF:0000044
  review:
    summary: ESCRT-III localization to nuclear envelope.
    action: ACCEPT
    reason: Core localization.

# exit from mitosis - IMP
- term:
    id: GO:0010458
    label: exit from mitosis
  evidence_type: IMP
  original_reference_id: PMID:26040712
  review:
    summary: ESCRT-III functions during mitotic exit.
    action: ACCEPT
    reason: Core function.

# chromatin - IDA
    supported_by:
    - reference_id: PMID:26040712
      supporting_text: Spastin and ESCRT-III coordinate mitotic spindle disassembly
        and nuclear envelope sealing.
- term:
    id: GO:0000785
    label: chromatin
  evidence_type: IDA
  original_reference_id: PMID:28242692
  review:
    summary: CHMP2A recruited to chromatin disks during NE reformation.
    action: ACCEPT
    reason: ESCRT-III recruited to anaphase chromatin for NE sealing.

# viral budding via host ESCRT complex - IDA (PMID:24878737)
    supported_by:
    - reference_id: PMID:28242692
      supporting_text: LEM2 recruits CHMP7 for ESCRT-mediated nuclear envelope closure
        in fission yeast and human cells.
- term:
    id: GO:0039702
    label: viral budding via host ESCRT complex
  evidence_type: IDA
  original_reference_id: PMID:24878737
  review:
    summary: ESCRT-III forms spirals around nascent HIV Gag assemblies.
    action: ACCEPT
    reason: Core function.
    supported_by:
    - reference_id: PMID:24878737
      supporting_text: "depleting Vps4 traps ESCRT-III filaments around nascent Gag\
        \ assemblies"

# viral budding via host ESCRT complex - IMP (PMID:23051622)
- term:
    id: GO:0039702
    label: viral budding via host ESCRT complex
  evidence_type: IMP
  original_reference_id: PMID:23051622
  review:
    summary: CHMP2A required for viral budding.
    action: ACCEPT
    reason: Core function.
    supported_by:
    - reference_id: PMID:23051622
      supporting_text: "CHMP3 contributes synergistically to HIV-1 budding, and the\
        \ CHMP3 contribution is ~ 10-fold more pronounced in concert with CHMP2A than\
        \ with CHMP2B"

# viral budding via host ESCRT complex - TAS
- term:
    id: GO:0039702
    label: viral budding via host ESCRT complex
  evidence_type: TAS
  original_reference_id: PMID:20588296
  review:
    summary: ESCRT-III involved in viral budding.
    action: ACCEPT
    reason: Core function.

# viral budding via host ESCRT complex - IEA
    supported_by:
    - reference_id: PMID:20588296
      supporting_text: "Jun 30. Membrane budding and scission by the ESCRT machinery:\
        \ it's all in the neck."
- term:
    id: GO:0039702
    label: viral budding via host ESCRT complex
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  review:
    summary: ESCRT-III required for viral budding.
    action: ACCEPT
    reason: Core function.

# viral budding via host ESCRT complex - IGI
- term:
    id: GO:0039702
    label: viral budding via host ESCRT complex
  evidence_type: IGI
  original_reference_id: PMID:24107264
  review:
    summary: CHMP2A genetic interaction in viral budding.
    action: ACCEPT
    reason: Core function - EIAV budding requires CHMP2A-VPS4 interactions.
    supported_by:
    - reference_id: PMID:24107264
      supporting_text: "EIAV budding was inhibited by point mutations that abrogate\
        \ the direct interactions between ALIX:CHMP4B, CHMP4B:CHMP2A, and CHMP2A:VPS4A/B"

# viral budding from plasma membrane - IDA
- term:
    id: GO:0046761
    label: viral budding from plasma membrane
  evidence_type: IDA
  original_reference_id: PMID:24878737
  review:
    summary: ESCRT-III functions at plasma membrane during viral budding.
    action: ACCEPT
    reason: Core function.

# viral budding from plasma membrane - IMP
    supported_by:
    - reference_id: PMID:24878737
      supporting_text: Structure of cellular ESCRT-III spirals and their relationship
        to HIV budding.
- term:
    id: GO:0046761
    label: viral budding from plasma membrane
  evidence_type: IMP
  original_reference_id: PMID:14505570
  review:
    summary: CHMP2A required for HIV-1 budding.
    action: ACCEPT
    reason: Core function for viral infection.
    supported_by:
    - reference_id: PMID:14505570
      supporting_text: "dominant-negative mutants of late-acting human class E proteins\
        \ arrested HIV-1 budding through plasmal and endosomal membranes"

# viral budding from plasma membrane - IEA
- term:
    id: GO:0046761
    label: viral budding from plasma membrane
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  review:
    summary: ESCRT-III required for viral budding from PM.
    action: ACCEPT
    reason: Core function.

# viral release from host cell - IMP
- term:
    id: GO:0019076
    label: viral release from host cell
  evidence_type: IMP
  original_reference_id: PMID:23051622
  review:
    summary: CHMP2A required for virus release.
    action: ACCEPT
    reason: Core function for viral budding.

# viral release from host cell - IGI (PMID:23051622 with Q9UQN3)
    supported_by:
    - reference_id: PMID:23051622
      supporting_text: ESCRT-III CHMP2A and CHMP3 form variable helical polymers in
        vitro and act synergistically during HIV-1 budding.
- term:
    id: GO:0019076
    label: viral release from host cell
  evidence_type: IGI
  original_reference_id: PMID:23051622
  review:
    summary: Genetic interaction with CHMP4A in viral release.
    action: ACCEPT
    reason: Core function.

# viral release from host cell - IGI (PMID:23051622 with Q9Y3E7)
    supported_by:
    - reference_id: PMID:23051622
      supporting_text: ESCRT-III CHMP2A and CHMP3 form variable helical polymers in
        vitro and act synergistically during HIV-1 budding.
- term:
    id: GO:0019076
    label: viral release from host cell
  evidence_type: IGI
  original_reference_id: PMID:23051622
  review:
    summary: Genetic interaction with CHMP3 in viral release.
    action: ACCEPT
    reason: Core function.

# autophagosome maturation - IMP
    supported_by:
    - reference_id: PMID:23051622
      supporting_text: ESCRT-III CHMP2A and CHMP3 form variable helical polymers in
        vitro and act synergistically during HIV-1 budding.
- term:
    id: GO:0097352
    label: autophagosome maturation
  evidence_type: IMP
  original_reference_id: PMID:17984323
  review:
    summary: ESCRT-III required for autophagosome maturation.
    action: ACCEPT
    reason: Core function - needed for phagophore closure.
    supported_by:
    - reference_id: PMID:17984323
      supporting_text: "autophagic degradation is inhibited in cells depleted of ESCRT\
        \ subunits"

# autophagosome maturation - IEA
- term:
    id: GO:0097352
    label: autophagosome maturation
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  review:
    summary: ESCRT required for autophagosome maturation.
    action: ACCEPT
    reason: Core function.

# autophagy - IMP
- term:
    id: GO:0006914
    label: autophagy
  evidence_type: IMP
  original_reference_id: PMID:17984323
  review:
    summary: ESCRT depletion impairs autophagic degradation.
    action: ACCEPT
    reason: Core function.

# macroautophagy - TAS
    supported_by:
    - reference_id: PMID:17984323
      supporting_text: Functional multivesicular bodies are required for autophagic
        clearance of protein aggregates associated with neurodegenerative disease.
- term:
    id: GO:0016236
    label: macroautophagy
  evidence_type: TAS
  original_reference_id: PMID:20588296
  review:
    summary: ESCRT-III required for macroautophagy.
    action: ACCEPT
    reason: Core function.

# autophagosome membrane - IDA
    supported_by:
    - reference_id: PMID:20588296
      supporting_text: "Jun 30. Membrane budding and scission by the ESCRT machinery:\
        \ it's all in the neck."
- term:
    id: GO:0000421
    label: autophagosome membrane
  evidence_type: IDA
  original_reference_id: PMID:17984323
  review:
    summary: CHMP2A localizes to autophagosome membranes.
    action: ACCEPT
    reason: Core localization.

# amphisome membrane - IDA
    supported_by:
    - reference_id: PMID:17984323
      supporting_text: Functional multivesicular bodies are required for autophagic
        clearance of protein aggregates associated with neurodegenerative disease.
- term:
    id: GO:1904930
    label: amphisome membrane
  evidence_type: IDA
  original_reference_id: PMID:17984323
  review:
    summary: CHMP2A localizes to amphisome membranes.
    action: ACCEPT
    reason: ESCRT-III functions at autophagosome-endosome fusion sites.

# amphisome membrane - IEA
    supported_by:
    - reference_id: PMID:17984323
      supporting_text: Functional multivesicular bodies are required for autophagic
        clearance of protein aggregates associated with neurodegenerative disease.
- term:
    id: GO:1904930
    label: amphisome membrane
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  review:
    summary: ESCRT-III localizes to amphisome membrane.
    action: ACCEPT
    reason: Core localization.

# plasma membrane repair - IDA
- term:
    id: GO:0001778
    label: plasma membrane repair
  evidence_type: IDA
  original_reference_id: PMID:24482116
  review:
    summary: ESCRT machinery required for plasma membrane repair.
    action: ACCEPT
    reason: Core function - ESCRT proteins recruited within seconds to wounds.
    supported_by:
    - reference_id: PMID:24482116
      supporting_text: "ESCRT proteins were recruited within seconds to plasma membrane\
        \ wounds"

# plasma membrane repair - IEA
- term:
    id: GO:0001778
    label: plasma membrane repair
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  review:
    summary: ESCRT machinery required for PM repair.
    action: ACCEPT
    reason: Core function.

# membrane fission - IDA
- term:
    id: GO:0090148
    label: membrane fission
  evidence_type: IDA
  original_reference_id: PMID:36604498
  review:
    summary: Direct evidence for CHMP2A membrane fission activity.
    action: ACCEPT
    reason: Core function.

# membrane fission - NAS
    supported_by:
    - reference_id: PMID:36604498
      supporting_text: Epub 2023 Jan 5. Structural basis of CHMP2A-CHMP3 ESCRT-III
        polymer assembly and membrane cleavage.
- term:
    id: GO:0090148
    label: membrane fission
  evidence_type: NAS
  original_reference_id: PMID:19234443
  review:
    summary: ESCRT-III mediates membrane fission.
    action: ACCEPT
    reason: Core function.
    supported_by:
    - reference_id: PMID:19234443
      supporting_text: "ESCRT-III has the instrinsic ability to drive the scission\
        \ of membrane necks"

# membrane bending activity - IDA
- term:
    id: GO:0180020
    label: membrane bending activity
  evidence_type: IDA
  original_reference_id: PMID:36604498
  review:
    summary: Direct evidence for CHMP2A membrane bending.
    action: ACCEPT
    reason: Core molecular function.

# membrane invagination - IMP
    supported_by:
    - reference_id: PMID:36604498
      supporting_text: Epub 2023 Jan 5. Structural basis of CHMP2A-CHMP3 ESCRT-III
        polymer assembly and membrane cleavage.
- term:
    id: GO:0010324
    label: membrane invagination
  evidence_type: IMP
  original_reference_id: PMID:24878737
  review:
    summary: ESCRT-III induces membrane invagination.
    action: ACCEPT
    reason: Core molecular function.

# phosphatidylcholine binding - IMP
    supported_by:
    - reference_id: PMID:24878737
      supporting_text: Structure of cellular ESCRT-III spirals and their relationship
        to HIV budding.
- term:
    id: GO:0031210
    label: phosphatidylcholine binding
  evidence_type: IMP
  original_reference_id: PMID:18687924
  review:
    summary: CHMP2A/CHMP3 polymers interact with lipid bilayers.
    action: ACCEPT
    reason: Molecular function - ESCRT-III binds membrane lipids.

# protein polymerization - IMP (PMID:23051622)
    supported_by:
    - reference_id: PMID:18687924
      supporting_text: Aug 7. Helical structures of ESCRT-III are disassembled by
        VPS4.
- term:
    id: GO:0051258
    label: protein polymerization
  evidence_type: IMP
  original_reference_id: PMID:23051622
  review:
    summary: ESCRT-III polymerizes into helical structures.
    action: ACCEPT
    reason: Core molecular activity.

# protein polymerization - IMP (PMID:24878737)
    supported_by:
    - reference_id: PMID:23051622
      supporting_text: ESCRT-III CHMP2A and CHMP3 form variable helical polymers in
        vitro and act synergistically during HIV-1 budding.
- term:
    id: GO:0051258
    label: protein polymerization
  evidence_type: IMP
  original_reference_id: PMID:24878737
  review:
    summary: ESCRT-III filament polymerization observed.
    action: ACCEPT
    reason: Core molecular activity.

# protein homooligomerization - IMP
    supported_by:
    - reference_id: PMID:24878737
      supporting_text: Structure of cellular ESCRT-III spirals and their relationship
        to HIV budding.
- term:
    id: GO:0051260
    label: protein homooligomerization
  evidence_type: IMP
  original_reference_id: PMID:18687924
  review:
    summary: CHMP2A can self-associate and copolymerize with CHMP3.
    action: ACCEPT
    reason: Molecular property of ESCRT-III subunits.

# protein domain specific binding - IPI (PMID:17928862 with O75351)
    supported_by:
    - reference_id: PMID:18687924
      supporting_text: Aug 7. Helical structures of ESCRT-III are disassembled by
        VPS4.
- term:
    id: GO:0019904
    label: protein domain specific binding
  evidence_type: IPI
  original_reference_id: PMID:17928862
  review:
    summary: VPS4 recognizes CHMP2A through MIT-MIM domain interaction.
    action: ACCEPT
    reason: Specific molecular function - CHMP2A contains MIM that binds VPS4 MIT
      domain.
    supported_by:
    - reference_id: PMID:17928862
      supporting_text: "the microtubule interacting and transport (MIT) domains of\
        \ human VPS4A and VPS4B bind conserved sequence motifs located at the carboxy\
        \ termini of the CHMP1-3 class of ESCRT-III proteins"

# protein domain specific binding - IPI (PMID:17928862 with Q9UN37)
- term:
    id: GO:0019904
    label: protein domain specific binding
  evidence_type: IPI
  original_reference_id: PMID:17928862
  review:
    summary: VPS4B MIT domain binds CHMP2A MIM.
    action: ACCEPT
    reason: Specific molecular function.

# ESCRT III complex disassembly - NAS
    supported_by:
    - reference_id: PMID:17928862
      supporting_text: ESCRT-III recognition by VPS4 ATPases.
- term:
    id: GO:1904903
    label: ESCRT III complex disassembly
  evidence_type: NAS
  original_reference_id: PMID:20588296
  review:
    summary: VPS4-mediated ESCRT-III disassembly is required for function.
    action: ACCEPT
    reason: Core regulatory process.

# cytosol - TAS (Reactome:R-HSA-917700)
    supported_by:
    - reference_id: PMID:20588296
      supporting_text: "Jun 30. Membrane budding and scission by the ESCRT machinery:\
        \ it's all in the neck."
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-917700
  review:
    summary: CHMP2A is cytosolic in autoinhibited state before membrane recruitment.
    action: ACCEPT
    reason: Accurate - ESCRT-III proteins exist in cytosol before activation.

# cytosol - TAS (Reactome:R-HSA-3159232)
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-3159232
  review:
    summary: CHMP2A cytosolic localization in ESCRT pathway.
    action: ACCEPT
    reason: Core localization when inactive.

# cytosol - TAS (Reactome:R-HSA-5671702)
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-5671702
  review:
    summary: CHMP2A cytosolic localization.
    action: ACCEPT
    reason: Core localization.

# cytosol - TAS (Reactome:R-HSA-917693)
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-917693
  review:
    summary: CHMP2A cytosolic localization.
    action: ACCEPT
    reason: Core localization.

# cytosol - TAS (Reactome:R-HSA-9668389)
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-9668389
  review:
    summary: CHMP2A cytosolic localization.
    action: ACCEPT
    reason: Core localization.

# cytosol - TAS (Reactome:R-HSA-9668395)
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-9668395
  review:
    summary: CHMP2A cytosolic localization.
    action: ACCEPT
    reason: Core localization.

# cytosol - TAS (Reactome:R-HSA-9668398)
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-9668398
  review:
    summary: CHMP2A cytosolic localization.
    action: ACCEPT
    reason: Core localization.

# cytosol - TAS (Reactome:R-HSA-9668405)
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-9668405
  review:
    summary: CHMP2A cytosolic localization.
    action: ACCEPT
    reason: Core localization.

# cytosol - TAS (Reactome:R-HSA-9668415)
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-9668415
  review:
    summary: CHMP2A cytosolic localization.
    action: ACCEPT
    reason: Core localization.

# cytosol - TAS (Reactome:R-HSA-9668419)
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-9668419
  review:
    summary: CHMP2A cytosolic localization.
    action: ACCEPT
    reason: Core localization.

# cytosol - IEA
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: CHMP2A cytosolic localization.
    action: ACCEPT
    reason: Core localization when inactive.

# plasma membrane - IDA
- term:
    id: GO:0005886
    label: plasma membrane
  evidence_type: IDA
  original_reference_id: PMID:24878737
  review:
    summary: CHMP2A localizes to plasma membrane during viral budding.
    action: ACCEPT
    reason: Core localization for viral budding function.

# lysosomal membrane - IDA
    supported_by:
    - reference_id: PMID:24878737
      supporting_text: Structure of cellular ESCRT-III spirals and their relationship
        to HIV budding.
- term:
    id: GO:0005765
    label: lysosomal membrane
  evidence_type: IDA
  original_reference_id: PMID:17984323
  review:
    summary: CHMP2A localizes to lysosomal membrane during autophagy.
    action: ACCEPT
    reason: ESCRT-III functions at autophagosome/MVB-lysosome interface.

# lysosomal membrane - IEA
    supported_by:
    - reference_id: PMID:17984323
      supporting_text: Functional multivesicular bodies are required for autophagic
        clearance of protein aggregates associated with neurodegenerative disease.
- term:
    id: GO:0005765
    label: lysosomal membrane
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  review:
    summary: ESCRT-III localization to lysosomal membrane.
    action: ACCEPT
    reason: Core localization.

# late endosome membrane - IEA
- term:
    id: GO:0031902
    label: late endosome membrane
  evidence_type: IEA
  original_reference_id: GO_REF:0000044
  review:
    summary: CHMP2A localizes to late endosome/MVB membranes.
    action: ACCEPT
    reason: Core localization.

# membrane - HDA
- term:
    id: GO:0016020
    label: membrane
  evidence_type: HDA
  original_reference_id: PMID:19946888
  review:
    summary: CHMP2A detected in membrane proteome.
    action: ACCEPT
    reason: General but accurate.

# membrane coat - IMP
    supported_by:
    - reference_id: PMID:19946888
      supporting_text: Defining the membrane proteome of NK cells.
- term:
    id: GO:0030117
    label: membrane coat
  evidence_type: IMP
  original_reference_id: PMID:24878737
  review:
    summary: ESCRT-III forms coat-like structures on membranes.
    action: ACCEPT
    reason: ESCRT-III polymers form membrane-associated coats/spirals.

# positive regulation of exosomal secretion - IMP
    supported_by:
    - reference_id: PMID:24878737
      supporting_text: Structure of cellular ESCRT-III spirals and their relationship
        to HIV budding.
- term:
    id: GO:1903543
    label: positive regulation of exosomal secretion
  evidence_type: IMP
  original_reference_id: PMID:22660413
  review:
    summary: ESCRT-III involved in exosome biogenesis.
    action: ACCEPT
    reason: Core function - MVB-derived exosomes require ESCRT.
    supported_by:
    - reference_id: PMID:22660413
      supporting_text: "Syntenin exosomes depend on the availability of heparan sulphate,\
        \ syndecans, ALIX and ESCRTs"

# extracellular exosome - HDA (PMID:23533145)
- term:
    id: GO:0070062
    label: extracellular exosome
  evidence_type: HDA
  original_reference_id: PMID:23533145
  review:
    summary: CHMP2A detected in exosome proteomics.
    action: KEEP_AS_NON_CORE
    reason: Detection expected given ESCRT role in exosome biogenesis.

# extracellular exosome - HDA (PMID:19056867)
    supported_by:
    - reference_id: PMID:23533145
      supporting_text: 2013 Apr 23. In-depth proteomic analyses of exosomes isolated
        from expressed prostatic secretions in urine.
- term:
    id: GO:0070062
    label: extracellular exosome
  evidence_type: HDA
  original_reference_id: PMID:19056867
  review:
    summary: CHMP2A detected in exosome proteomics.
    action: KEEP_AS_NON_CORE
    reason: Detection expected given ESCRT role in exosome biogenesis.

# extracellular exosome - HDA (PMID:20458337)
    supported_by:
    - reference_id: PMID:19056867
      supporting_text: 2008 Dec 3. Large-scale proteomics and phosphoproteomics of
        urinary exosomes.
- term:
    id: GO:0070062
    label: extracellular exosome
  evidence_type: HDA
  original_reference_id: PMID:20458337
  review:
    summary: CHMP2A detected in exosome proteomics.
    action: KEEP_AS_NON_CORE
    reason: Detection expected given ESCRT role in exosome biogenesis.

# kinetochore - IDA
    supported_by:
    - reference_id: PMID:20458337
      supporting_text: 2010 May 11. MHC class II-associated proteins in B-cell exosomes
        and potential functional implications for exosome biogenesis.
- term:
    id: GO:0000776
    label: kinetochore
  evidence_type: IDA
  original_reference_id: PMID:26040712
  review:
    summary: ESCRT-III proteins localize to kinetochores during mitosis.
    action: KEEP_AS_NON_CORE
    reason: Non-core localization.

# kinetochore - IEA
    supported_by:
    - reference_id: PMID:26040712
      supporting_text: Spastin and ESCRT-III coordinate mitotic spindle disassembly
        and nuclear envelope sealing.
- term:
    id: GO:0000776
    label: kinetochore
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  review:
    summary: ESCRT-III localization to kinetochore.
    action: KEEP_AS_NON_CORE
    reason: Non-core localization.

# kinetochore microtubule - IDA
- term:
    id: GO:0005828
    label: kinetochore microtubule
  evidence_type: IDA
  original_reference_id: PMID:26040712
  review:
    summary: ESCRT-III recruited to sites where NE engulfs spindle microtubules.
    action: KEEP_AS_NON_CORE
    reason: Non-core localization.

# kinetochore microtubule - IEA
    supported_by:
    - reference_id: PMID:26040712
      supporting_text: Spastin and ESCRT-III coordinate mitotic spindle disassembly
        and nuclear envelope sealing.
- term:
    id: GO:0005828
    label: kinetochore microtubule
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  review:
    summary: ESCRT-III localization to kinetochore microtubule.
    action: KEEP_AS_NON_CORE
    reason: Non-core localization.

# nuclear pore - IEA
- term:
    id: GO:0005643
    label: nuclear pore
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  review:
    summary: ESCRT-III implicated in NPC surveillance in yeast.
    action: KEEP_AS_NON_CORE
    reason: Primary function is NE sealing rather than NPC-specific activity.

# mitotic metaphase chromosome alignment - IMP
- term:
    id: GO:0007080
    label: mitotic metaphase chromosome alignment
  evidence_type: IMP
  original_reference_id: PMID:20616062
  review:
    summary: CHMP2A depletion causes chromosome alignment defects.
    action: KEEP_AS_NON_CORE
    reason: Secondary effect of centrosome/spindle defects.

# mitotic metaphase chromosome alignment - IEA
    supported_by:
    - reference_id: PMID:20616062
      supporting_text: Human ESCRT-III and VPS4 proteins are required for centrosome
        and spindle maintenance.
- term:
    id: GO:0007080
    label: mitotic metaphase chromosome alignment
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  review:
    summary: ESCRT-III role in chromosome alignment.
    action: KEEP_AS_NON_CORE
    reason: Secondary effect.

# nucleus organization - IMP
- term:
    id: GO:0006997
    label: nucleus organization
  evidence_type: IMP
  original_reference_id: PMID:20616062
  review:
    summary: ESCRT-III depletion causes nuclear morphology defects.
    action: KEEP_AS_NON_CORE
    reason: Secondary effect of spindle/centrosome defects.

# regulation of mitotic spindle assembly - IMP
    supported_by:
    - reference_id: PMID:20616062
      supporting_text: Human ESCRT-III and VPS4 proteins are required for centrosome
        and spindle maintenance.
- term:
    id: GO:1901673
    label: regulation of mitotic spindle assembly
  evidence_type: IMP
  original_reference_id: PMID:20616062
  review:
    summary: CHMP2A depletion causes spindle defects.
    action: KEEP_AS_NON_CORE
    reason: Secondary effect on spindles.

# regulation of mitotic spindle assembly - IEA
    supported_by:
    - reference_id: PMID:20616062
      supporting_text: Human ESCRT-III and VPS4 proteins are required for centrosome
        and spindle maintenance.
- term:
    id: GO:1901673
    label: regulation of mitotic spindle assembly
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  review:
    summary: ESCRT-III role in spindle assembly regulation.
    action: KEEP_AS_NON_CORE
    reason: Secondary effect.

# regulation of centrosome duplication - IMP
- term:
    id: GO:0010824
    label: regulation of centrosome duplication
  evidence_type: IMP
  original_reference_id: PMID:20616062
  review:
    summary: ESCRT-III depletion causes centrosome abnormalities.
    action: KEEP_AS_NON_CORE
    reason: Non-core function.

# negative regulation of centriole elongation - IMP
    supported_by:
    - reference_id: PMID:20616062
      supporting_text: Human ESCRT-III and VPS4 proteins are required for centrosome
        and spindle maintenance.
- term:
    id: GO:1903723
    label: negative regulation of centriole elongation
  evidence_type: IMP
  original_reference_id: PMID:20616062
  review:
    summary: ESCRT-III may regulate centriole elongation.
    action: KEEP_AS_NON_CORE
    reason: Indirect effect through centrosome maintenance.

# protein transport - IBA
    supported_by:
    - reference_id: PMID:20616062
      supporting_text: Human ESCRT-III and VPS4 proteins are required for centrosome
        and spindle maintenance.
- term:
    id: GO:0015031
    label: protein transport
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    summary: CHMP2A participates in protein transport through MVB-mediated sorting.
    action: ACCEPT
    reason: Broadly accurate but general.

# protein transport - IEA
- term:
    id: GO:0015031
    label: protein transport
  evidence_type: IEA
  original_reference_id: GO_REF:0000043
  review:
    summary: CHMP2A functions in protein transport.
    action: ACCEPT
    reason: Broadly accurate.

# vacuolar transport - IEA
- term:
    id: GO:0007034
    label: vacuolar transport
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  review:
    summary: CHMP2A functions in vacuolar/lysosomal transport.
    action: ACCEPT
    reason: Core ESCRT-III function.

# vesicle fusion with vacuole - NAS
- term:
    id: GO:0051469
    label: vesicle fusion with vacuole
  evidence_type: NAS
  original_reference_id: PMID:16505166
  review:
    summary: ESCRT function required for MVB-lysosome fusion.
    action: ACCEPT
    reason: Core function.

# establishment of protein localization - IMP
    supported_by:
    - reference_id: PMID:16505166
      supporting_text: Recycling of ESCRTs by the AAA-ATPase Vps4 is regulated by
        a conserved VSL region in Vta1.
- term:
    id: GO:0045184
    label: establishment of protein localization
  evidence_type: IMP
  original_reference_id: PMID:23045692
  review:
    summary: CHMP2A involved in protein localization through MITD1 interaction.
    action: KEEP_AS_NON_CORE
    reason: General term - more specific functions captured elsewhere.
    supported_by:
    - reference_id: PMID:23045692
      supporting_text: "the MIT domain binds to a subset of ESCRT-III subunits and\
        \ that this interaction mediates MITD1 recruitment to the midbody during cytokinesis"

# protein binding - IPI (PMID:16730941 - multiple interactors)
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:16730941
  review:
    summary: CHMP2A interacts with MIT domain-containing proteins.
    action: MARK_AS_OVER_ANNOTATED
    reason: Generic - specific interaction with MITD1 or VPS4 is more informative.
    supported_by:
    - reference_id: PMID:16730941
      supporting_text: "two further MIT domain-containing proteins (AMSH/STAMBP and\
        \ LOC129531) interact with multiple components of the human ESCRT III complex"

# protein binding - IPI (PMID:19525971)
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:19525971
  review:
    summary: CHMP2A interacts with CHMP3.
    action: MARK_AS_OVER_ANNOTATED
    reason: Generic - specific ESCRT-III complex membership is more informative.

# protein binding - IPI (PMID:23051622)
    supported_by:
    - reference_id: PMID:19525971
      supporting_text: Jun 14. Structural basis for ESCRT-III protein autoinhibition.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:23051622
  review:
    summary: CHMP2A interacts with CHMP4B and CHMP3.
    action: MARK_AS_OVER_ANNOTATED
    reason: Generic - specific ESCRT-III complex membership is more informative.

# protein binding - IPI (PMID:25416956)
    supported_by:
    - reference_id: PMID:23051622
      supporting_text: ESCRT-III CHMP2A and CHMP3 form variable helical polymers in
        vitro and act synergistically during HIV-1 budding.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:25416956
  review:
    summary: Protein interaction detected.
    action: MARK_AS_OVER_ANNOTATED
    reason: Generic protein binding term.

# protein binding - IPI (PMID:26496610)
    supported_by:
    - reference_id: PMID:25416956
      supporting_text: A proteome-scale map of the human interactome network.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:26496610
  review:
    summary: Protein interaction detected.
    action: MARK_AS_OVER_ANNOTATED
    reason: Generic protein binding term.

# protein binding - IPI (PMID:28514442)
    supported_by:
    - reference_id: PMID:26496610
      supporting_text: Oct 22. A human interactome in three quantitative dimensions
        organized by stoichiometries and abundances.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:28514442
  review:
    summary: Protein interaction detected.
    action: MARK_AS_OVER_ANNOTATED
    reason: Generic protein binding term.

# protein binding - IPI (PMID:32296183)
    supported_by:
    - reference_id: PMID:28514442
      supporting_text: Architecture of the human interactome defines protein communities
        and disease networks.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:32296183
  review:
    summary: Protein interaction detected.
    action: MARK_AS_OVER_ANNOTATED
    reason: Generic protein binding term.

# protein binding - IPI (PMID:32814053)
    supported_by:
    - reference_id: PMID:32296183
      supporting_text: Apr 8. A reference map of the human binary protein interactome.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:32814053
  review:
    summary: Protein interaction detected.
    action: MARK_AS_OVER_ANNOTATED
    reason: Generic protein binding term.

# protein binding - IPI (PMID:33961781)
    supported_by:
    - reference_id: PMID:32814053
      supporting_text: Interactome Mapping Provides a Network of Neurodegenerative
        Disease Proteins and Uncovers Widespread Protein Aggregation in Affected Brains.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:33961781
  review:
    summary: Protein interaction detected.
    action: MARK_AS_OVER_ANNOTATED
    reason: Generic protein binding term.

# protein binding - IPI (PMID:35271311)
    supported_by:
    - reference_id: PMID:33961781
      supporting_text: 2021 May 6. Dual proteome-scale networks reveal cell-specific
        remodeling of the human interactome.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:35271311
  review:
    summary: Protein interaction detected.
    action: MARK_AS_OVER_ANNOTATED
    reason: Generic protein binding term.

# protein binding - IPI (PMID:18687924)
    supported_by:
    - reference_id: PMID:35271311
      supporting_text: '2022 Mar 11. OpenCell: Endogenous tagging for the cartography
        of human cellular organization.'
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:18687924
  review:
    summary: CHMP2A interacts with CHMP3 and VPS4B.
    action: MARK_AS_OVER_ANNOTATED
    reason: Generic - specific ESCRT-III polymerization and VPS4 interaction are more
      informative.

# protein binding - IPI (PMID:18385515)
    supported_by:
    - reference_id: PMID:18687924
      supporting_text: Aug 7. Helical structures of ESCRT-III are disassembled by
        VPS4.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:18385515
  review:
    summary: Protein interaction detected.
    action: MARK_AS_OVER_ANNOTATED
    reason: Generic protein binding term.

# protein binding - IPI (PMID:23105106)
    supported_by:
    - reference_id: PMID:18385515
      supporting_text: Apr 2. Novel interactions of ESCRT-III with LIP5 and VPS4 and
        their implications for ESCRT-III disassembly.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:23105106
  review:
    summary: Protein interaction detected.
    action: MARK_AS_OVER_ANNOTATED
    reason: Generic protein binding term.

# protein binding - IPI (PMID:14505570)
    supported_by:
    - reference_id: PMID:23105106
      supporting_text: 2012 Oct 26. Interactions of the human LIP5 regulatory protein
        with endosomal sorting complexes required for transport.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:14505570
  review:
    summary: CHMP2A interacts with VPS4 and other class E proteins.
    action: MARK_AS_OVER_ANNOTATED
    reason: Generic - specific domain binding more informative.
    supported_by:
    - reference_id: PMID:14505570
      supporting_text: "These proteins were connected into a coherent network by 43\
        \ different protein-protein interactions"

# protein binding - IPI (PMID:14519844)
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:14519844
  review:
    summary: Protein interaction detected.
    action: MARK_AS_OVER_ANNOTATED
    reason: Generic protein binding term.

# protein binding - IPI (PMID:21975012)
    supported_by:
    - reference_id: PMID:14519844
      supporting_text: Divergent retroviral late-budding domains recruit vacuolar
        protein sorting factors by using alternative adaptor proteins.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:21975012
  review:
    summary: Protein interaction detected.
    action: MARK_AS_OVER_ANNOTATED
    reason: Generic protein binding term.

# protein binding - IPI (PMID:23045692)
    supported_by:
    - reference_id: PMID:21975012
      supporting_text: ESCRT-III subunits Snf7-1 and Snf7-2 differentially regulate
        transmembrane cargos in hESC-derived human neurons.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:23045692
  review:
    summary: CHMP2A interacts with MITD1.
    action: MARK_AS_OVER_ANNOTATED
    reason: Generic - specific MIT-MIM domain interaction captured elsewhere.

# protein binding - IPI (PMID:21543490)
    supported_by:
    - reference_id: PMID:23045692
      supporting_text: ESCRT-III binding protein MITD1 is involved in cytokinesis
        and has an unanticipated PLD fold that binds membranes.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:21543490
  review:
    summary: Protein interaction detected.
    action: MARK_AS_OVER_ANNOTATED
    reason: Generic protein binding term.

# protein binding - IPI (PMID:19129480)
    supported_by:
    - reference_id: PMID:21543490
      supporting_text: Mechanism of inhibition of retrovirus release from cells by
        interferon-induced gene ISG15.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:19129480
  review:
    summary: Protein interaction detected.
    action: MARK_AS_OVER_ANNOTATED
    reason: Generic protein binding term.

    supported_by:
    - reference_id: PMID:19129480
      supporting_text: Jan 7. Essential role of hIST1 in cytokinesis.
core_functions:
- molecular_function:
    id: GO:0180020
    label: membrane bending activity
  description: >-
    CHMP2A is a core ESCRT-III subunit that copolymerizes with CHMP3 to form helical
    filaments on membranes, driving intraluminal vesicle formation during MVB biogenesis.
  directly_involved_in:
  - id: GO:0071985
    label: multivesicular body sorting pathway
  locations:
  - id: GO:0032585
    label: multivesicular body membrane
  in_complex:
    id: GO:0000815
    label: ESCRT III complex
  supported_by:
  - reference_id: PMID:16554368
    supporting_text: "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"
  - reference_id: PMID:18687924
    supporting_text: "We found that the ESCRT-III proteins CHMP2A and CHMP3 (charged\
      \ multivesicular body proteins 2A and 3) could assemble in vitro into helical\
      \ tubular structures"

- molecular_function:
    id: GO:0180020
    label: membrane bending activity
  description: >-
    CHMP2A forms helical filaments at the midbody that mediate membrane scission
    during cytokinetic abscission.
  directly_involved_in:
  - id: GO:0061952
    label: midbody abscission
  locations:
  - id: GO:0030496
    label: midbody
  in_complex:
    id: GO:0000815
    label: ESCRT III complex
  supported_by:
  - reference_id: PMID:20616062
    supporting_text: "We found that depletion of VPS4A, VPS4B, or any of the 11 different\
      \ human ESCRT-III (CHMP) proteins inhibited abscission"

- molecular_function:
    id: GO:0180020
    label: membrane bending activity
  description: >-
    CHMP2A is recruited to the reforming nuclear envelope during late anaphase via
    the LEM2-CHMP7 pathway, sealing NE at sites where it engulfs spindle microtubules.
  directly_involved_in:
  - id: GO:0031468
    label: nuclear membrane reassembly
  locations:
  - id: GO:0005635
    label: nuclear envelope
  in_complex:
    id: GO:0000815
    label: ESCRT III complex
  supported_by:
  - reference_id: PMID:26040712
    supporting_text: "We propose that ESCRT-III, VPS4 and spastin cooperate to coordinate\
      \ nuclear envelope sealing and spindle disassembly"
  - reference_id: PMID:26040713
    supporting_text: "The ESCRT-III component charged multivesicular body protein\
      \ 2A (CHMP2A) is directed to the forming NE through binding to CHMP4B, and provides\
      \ an activity essential for NE reformation."

- molecular_function:
    id: GO:0180020
    label: membrane bending activity
  description: >-
    CHMP2A is hijacked by HIV-1 and other enveloped viruses for membrane scission
    during viral budding from the plasma membrane.
  directly_involved_in:
  - id: GO:0039702
    label: viral budding via host ESCRT complex
  locations:
  - id: GO:0005886
    label: plasma membrane
  in_complex:
    id: GO:0000815
    label: ESCRT III complex
  supported_by:
  - reference_id: PMID:24878737
    supporting_text: "depleting Vps4 traps ESCRT-III filaments around nascent Gag\
      \ assemblies"

- molecular_function:
    id: GO:0180020
    label: membrane bending activity
  description: >-
    CHMP2A is required for phagophore closure to form sealed autophagosomes.
  directly_involved_in:
  - id: GO:0097352
    label: autophagosome maturation
  locations:
  - id: GO:0000421
    label: autophagosome membrane
  in_complex:
    id: GO:0000815
    label: ESCRT III complex
  supported_by:
  - reference_id: PMID:17984323
    supporting_text: "autophagic degradation is inhibited in cells depleted of ESCRT\
      \ subunits"

- molecular_function:
    id: GO:0180020
    label: membrane bending activity
  description: >-
    CHMP2A is recruited within seconds to plasma membrane wounds where ESCRT
    machinery mediates repair via extracellular shedding of damaged membrane.
  directly_involved_in:
  - id: GO:0001778
    label: plasma membrane repair
  locations:
  - id: GO:0005886
    label: plasma membrane
  in_complex:
    id: GO:0000815
    label: ESCRT III complex
  supported_by:
  - reference_id: PMID:24482116
    supporting_text: "ESCRT proteins were recruited within seconds to plasma membrane\
      \ wounds"

references:
- id: GO_REF:0000002
  title: Gene Ontology annotation through InterPro
  findings:
  - statement: Annotations based on InterPro domain assignments.

- id: GO_REF:0000033
  title: Annotation inferred from PAINT phylogenetic analysis
  findings:
  - statement: Phylogenetic annotation based on PANTHER.

- id: GO_REF:0000043
  title: Gene Ontology annotation based on UniProt keywords
  findings:
  - statement: Annotations derived from UniProt keywords.

- id: GO_REF:0000044
  title: Gene Ontology annotation through UniProt subcellular localization
  findings:
  - statement: Annotations based on UniProt subcellular localization data.

- id: GO_REF:0000107
  title: Gene Ontology annotation by Ensembl compara
  findings:
  - statement: Annotations inferred from orthology.

- id: GO_REF:0000117
  title: ARBA annotation
  findings:
  - statement: Annotations based on UniProt ARBA rules.

- id: Reactome:R-HSA-917700
  title: Reactome pathway annotation
  findings:
  - statement: CHMP2A localization in ESCRT-related Reactome pathways.

- id: PMID:14505570
  title: The protein network of HIV budding.
  findings:
  - statement: CHMP2A is part of the class E protein network required for HIV-1 budding.
    supporting_text: "dominant-negative mutants of late-acting human class E proteins\
      \ arrested HIV-1 budding through plasmal and endosomal membranes"

- id: PMID:16505166
  title: "Recycling of ESCRTs by the AAA-ATPase Vps4 is regulated by a conserved VSL\
    \ region in Vta1."
  findings:
  - statement: Review of ESCRT machinery and Vps4-mediated recycling.

- id: PMID:16554368
  title: "The ESCRT-III subunit hVps24 is required for degradation but not silencing\
    \ of the epidermal growth factor receptor."
  findings:
  - statement: hVps24 depletion impairs EGFR degradation and MVB-lysosome fusion.
    supporting_text: "Depletion of hVps24 by siRNA showed that this ESCRT subunit,\
      \ like Tsg101, is important for degradation of the epidermal growth factor (EGF)\
      \ receptor (EGFR)"

- id: PMID:16730941
  title: "A systematic analysis of human CHMP protein interactions: additional MIT\
    \ domain-containing proteins bind to multiple components of the human ESCRT III\
    \ complex."
  findings:
  - statement: CHMP2A interacts with MITD1 via its MIT domain.
    supporting_text: "two further MIT domain-containing proteins (AMSH/STAMBP and\
      \ LOC129531) interact with multiple components of the human ESCRT III complex"

- id: PMID:17928862
  title: ESCRT-III recognition by VPS4 ATPases.
  findings:
  - statement: VPS4 MIT domain recognizes CHMP2A MIM element.
    supporting_text: "the microtubule interacting and transport (MIT) domains of human\
      \ VPS4A and VPS4B bind conserved sequence motifs located at the carboxy termini\
      \ of the CHMP1-3 class of ESCRT-III proteins"

- id: PMID:17984323
  title: "Functional multivesicular bodies are required for autophagic clearance of\
    \ protein aggregates associated with neurodegenerative disease."
  findings:
  - statement: ESCRT depletion impairs autophagic degradation and causes ubiquitin-positive
      aggregate accumulation.
    supporting_text: "autophagic degradation is inhibited in cells depleted of ESCRT\
      \ subunits and in cells expressing CHMP2B mutants, leading to accumulation of\
      \ protein aggregates containing ubiquitinated proteins"

- id: PMID:18687924
  title: Helical structures of ESCRT-III are disassembled by VPS4.
  findings:
  - statement: CHMP2A and CHMP3 copolymerize into helical tubular structures.
    supporting_text: "We found that the ESCRT-III proteins CHMP2A and CHMP3 (charged\
      \ multivesicular body proteins 2A and 3) could assemble in vitro into helical\
      \ tubular structures"

- id: PMID:19234443
  title: Membrane scission by the ESCRT-III complex.
  findings:
  - statement: ESCRT-III has the intrinsic ability to drive membrane scission.
    supporting_text: "ESCRT-III has the instrinsic ability to drive the scission of\
      \ membrane necks"

- id: PMID:19946888
  title: Defining the membrane proteome of NK cells.
  findings:
  - statement: CHMP2A detected in membrane proteome.

- id: PMID:20588296
  title: "Membrane budding and scission by the ESCRT machinery: it's all in the neck."
  findings:
  - statement: Review of ESCRT-III in MVB formation, viral budding, and cytokinesis.
    supporting_text: "ESCRT-III-mediated membrane neck cleavage is crucial for many\
      \ processes, including the biogenesis of multivesicular bodies, viral budding,\
      \ cytokinesis, and probably autophagy"

- id: PMID:20616062
  title: "Human ESCRT-III and VPS4 proteins are required for centrosome and spindle\
    \ maintenance."
  findings:
  - statement: All 11 ESCRT-III proteins required for abscission; CHMP2A depletion
      causes monopolar spindles.
    supporting_text: "We found that depletion of VPS4A, VPS4B, or any of the 11 different\
      \ human ESCRT-III (CHMP) proteins inhibited abscission"

- id: PMID:22660413
  title: Syndecan-syntenin-ALIX regulates the biogenesis of exosomes.
  findings:
  - statement: ESCRT-III involved in exosome secretion.
    supporting_text: "Syntenin exosomes depend on the availability of heparan sulphate,\
      \ syndecans, ALIX and ESCRTs"

- id: PMID:23045692
  title: "ESCRT-III binding protein MITD1 is involved in cytokinesis and has an unanticipated\
    \ PLD fold that binds membranes."
  findings:
  - statement: CHMP2A involved in protein localization through MITD1.
    supporting_text: "the MIT domain binds to a subset of ESCRT-III subunits and that\
      \ this interaction mediates MITD1 recruitment to the midbody during cytokinesis"

- id: PMID:23051622
  title: "ESCRT-III CHMP2A and CHMP3 form variable helical polymers in vitro and act\
    \ synergistically during HIV-1 budding."
  findings:
  - statement: CHMP2A required for viral release.
    supporting_text: "CHMP3 contributes synergistically to HIV-1 budding, and the\
      \ CHMP3 contribution is ~ 10-fold more pronounced in concert with CHMP2A than\
      \ with CHMP2B"

- id: PMID:23533145
  title: "In-depth proteomic analyses of exosomes isolated from expressed prostatic\
    \ secretions in urine."
  findings:
  - statement: CHMP2A detected in exosome proteome.

- id: PMID:24107264
  title: ESCRT requirements for EIAV budding.
  findings:
  - statement: CHMP2A-VPS4 interaction required for EIAV budding.
    supporting_text: "EIAV budding was inhibited by point mutations that abrogate\
      \ the direct interactions between ALIX:CHMP4B, CHMP4B:CHMP2A, and CHMP2A:VPS4A/B"

- id: PMID:24482116
  title: "ESCRT machinery is required for plasma membrane repair."
  findings:
  - statement: ESCRT proteins recruited within seconds to plasma membrane wounds.
    supporting_text: "ESCRT proteins were recruited within seconds to plasma membrane\
      \ wounds"

- id: PMID:24878737
  title: "Structure of cellular ESCRT-III spirals and their relationship to HIV budding."
  findings:
  - statement: ESCRT-III forms membrane-deforming conical spirals; VPS4 depletion
      traps filaments around HIV Gag.
    supporting_text: "depleting Vps4 traps ESCRT-III filaments around nascent Gag\
      \ assemblies"

- id: PMID:26040712
  title: "Spastin and ESCRT-III coordinate mitotic spindle disassembly and nuclear\
    \ envelope sealing."
  findings:
  - statement: ESCRT-III transiently recruited to reforming NE during late anaphase.
    supporting_text: "We propose that ESCRT-III, VPS4 and spastin cooperate to coordinate\
      \ nuclear envelope sealing and spindle disassembly"

- id: PMID:26040713
  title: ESCRT-III controls nuclear envelope reformation.
  findings:
  - statement: CHMP2A is essential for NE sealing.
    supporting_text: "The ESCRT-III component charged multivesicular body protein\
      \ 2A (CHMP2A) is directed to the forming NE through binding to CHMP4B, and provides\
      \ an activity essential for NE reformation."

- id: PMID:28242692
  title: "LEM2 recruits CHMP7 for ESCRT-mediated nuclear envelope closure in fission yeast and human cells."
  findings:
  - statement: CHMP2A recruitment to chromatin disks depends on LEM2-CHMP7 pathway.

- id: PMID:36604498
  title: "Structural basis of CHMP2A-CHMP3 ESCRT-III polymer assembly and membrane\
    \ cleavage."
  findings:
  - statement: Direct demonstration of CHMP2A membrane fission and bending activities.

- id: file:human/CHMP2A/CHMP2A-deep-research-falcon.md
  title: Deep research review of CHMP2A function
  findings:
  - statement: CHMP2A is a core ESCRT-III subunit required for phagophore closure,
      cytokinetic abscission, NE sealing, and viral budding.

# Reactome pathway references
- id: Reactome:R-HSA-3159232
  title: Reactome pathway - ESCRT-mediated membrane scission
  findings:
  - statement: CHMP2A participates in ESCRT-mediated membrane scission pathways.

- id: Reactome:R-HSA-5671702
  title: Reactome pathway - ESCRT-III recruitment to midbody
  findings:
  - statement: CHMP2A recruited to midbody for abscission.

- id: Reactome:R-HSA-917693
  title: Reactome pathway - Autophagic flux
  findings:
  - statement: CHMP2A is part of ESCRT machinery in autophagy.

- id: Reactome:R-HSA-9668389
  title: Reactome pathway - Nuclear envelope sealing
  findings:
  - statement: CHMP2A participates in nuclear envelope sealing.

- id: Reactome:R-HSA-9668395
  title: Reactome pathway - ESCRT complex assembly
  findings:
  - statement: CHMP2A is recruited to ESCRT-III complexes.

- id: Reactome:R-HSA-9668398
  title: Reactome pathway - Membrane scission
  findings:
  - statement: CHMP2A involved in ESCRT-mediated membrane scission.

- id: Reactome:R-HSA-9668405
  title: Reactome pathway - MVB formation
  findings:
  - statement: CHMP2A participates in MVB biogenesis.

- id: Reactome:R-HSA-9668415
  title: Reactome pathway - Viral budding
  findings:
  - statement: CHMP2A hijacked by viruses for budding.

- id: Reactome:R-HSA-9668419
  title: Reactome pathway - Plasma membrane repair
  findings:
  - statement: CHMP2A involved in plasma membrane wound repair.

# Additional PMID references from GOA
- id: PMID:19056867
  title: Large-scale proteomics and phosphoproteomics of urinary exosomes.
  findings:
  - statement: CHMP2A detected in exosome proteome.

- id: PMID:20458337
  title: MHC class II-associated proteins in B-cell exosomes and potential functional
    implications for exosome biogenesis.
  findings:
  - statement: CHMP2A detected in exosome proteome.

- id: PMID:19525971
  title: Structural basis for ESCRT-III protein autoinhibition.
  findings:
  - statement: CHMP2A interacts with CHMP3 in ESCRT-III complex.

- id: PMID:25416956
  title: A proteome-scale map of the human interactome network.
  findings:
  - statement: Protein-protein interaction detected.

- id: PMID:26496610
  title: A human interactome in three quantitative dimensions organized by stoichiometries
    and abundances.
  findings:
  - statement: Protein-protein interaction detected.

- id: PMID:28514442
  title: Architecture of the human interactome defines protein communities and disease
    networks.
  findings:
  - statement: Protein-protein interaction detected.

- id: PMID:32296183
  title: A reference map of the human binary protein interactome.
  findings:
  - statement: Protein-protein interaction detected.

- id: PMID:32814053
  title: Interactome Mapping Provides a Network of Neurodegenerative Disease Proteins
    and Uncovers Widespread Protein Aggregation in Affected Brains.
  findings:
  - statement: Protein-protein interaction detected.

- id: PMID:33961781
  title: Dual proteome-scale networks reveal cell-specific remodeling of the human
    interactome.
  findings:
  - statement: Protein-protein interaction detected.

- id: PMID:35271311
  title: "OpenCell: Endogenous tagging for the cartography of human cellular organization."
  findings:
  - statement: Protein-protein interaction detected.

- id: PMID:18385515
  title: Novel interactions of ESCRT-III with LIP5 and VPS4 and their implications
    for ESCRT-III disassembly.
  findings:
  - statement: CHMP2A interacts with ESCRT-III related proteins.

- id: PMID:23105106
  title: Interactions of the human LIP5 regulatory protein with endosomal sorting
    complexes required for transport.
  findings:
  - statement: CHMP2A interacts with ESCRT-III related proteins.

- id: PMID:14519844
  title: Divergent retroviral late-budding domains recruit vacuolar protein sorting
    factors by using alternative adaptor proteins.
  findings:
  - statement: CHMP2A interacts with class E proteins.

- id: PMID:21975012
  title: ESCRT-III subunits Snf7-1 and Snf7-2 differentially regulate transmembrane
    cargos in hESC-derived human neurons.
  findings:
  - statement: Protein-protein interaction detected.

- id: PMID:21543490
  title: Mechanism of inhibition of retrovirus release from cells by interferon-induced
    gene ISG15.
  findings:
  - statement: Protein-protein interaction detected.

- id: PMID:19129480
  title: Essential role of hIST1 in cytokinesis.
  findings:
  - statement: Protein-protein interaction detected.

Gene Description

Existing Annotations Review

Core Functions

CHMP2A is a core ESCRT-III subunit that copolymerizes with CHMP3 to form helical filaments on membranes, driving intraluminal vesicle formation during MVB biogenesis.

CHMP2A forms helical filaments at the midbody that mediate membrane scission during cytokinetic abscission.

CHMP2A is recruited to the reforming nuclear envelope during late anaphase via the LEM2-CHMP7 pathway, sealing NE at sites where it engulfs spindle microtubules.

CHMP2A is hijacked by HIV-1 and other enveloped viruses for membrane scission during viral budding from the plasma membrane.

CHMP2A is required for phagophore closure to form sealed autophagosomes.

CHMP2A is recruited within seconds to plasma membrane wounds where ESCRT machinery mediates repair via extracellular shedding of damaged membrane.

References

Deep Research

Falcon

Citations

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