Existing Annotations Review

GO Term	Evidence	Action	Reason
GO:0043162 ubiquitin-dependent protein catabolic process via the multivesicular body sorting pathway	IBA GO_REF:0000033	ACCEPT	Summary: ubiquitin-dependent protein catabolic process via the multivesicular body sorting pathway is supported as part of the core VPS37A/ESCRT-I endosomal cargo-sorting role. Reason: VPS37A is required for ESCRT-I-dependent sorting of ubiquitinated endocytic cargos, including EGFR, into MVB/lysosomal routes. Supporting Evidence: file:human/VPS37A/VPS37A-uniprot.txt Required for the sorting of endocytic file:human/VPS37A/VPS37A-uniprot.txt ubiquitinated cargos into multivesicular bodies PMID:15240819 retards epidermal growth factor (EGF) receptor degradation PMID:15240819 essential for lysosomal sorting of EGF receptors PMID:21757351 required for sorting EGFR to the MVB
GO:0000813 ESCRT I complex	IBA GO_REF:0000033	ACCEPT	Summary: ESCRT-I complex membership is the central VPS37A cellular-component annotation. Reason: VPS37A is the VPS37-family ESCRT-I subunit in TSG101-VPS28-VPS37-MVB12/UBAP variant complexes. Supporting Evidence: file:human/VPS37A/VPS37A-uniprot.txt Component of the ESCRT-I complex file:human/VPS37A/VPS37A-uniprot.txt which consists of TSG101, VPS28, a VPS37 file:human/VPS37A/VPS37A-uniprot.txt Interacts with TSG101, VPS28 and HGS PMID:15240819 a subunit of mammalian ESCRT-I PMID:21757351 Mammalian ESCRT-I comprises TSG101, VPS28, VPS37A-D, and MVB12A/B
GO:0006612 protein targeting to membrane	IBA GO_REF:0000033	MODIFY	Summary: Protein targeting to membrane is too broad for the VPS37A phagophore recruitment role. Reason: The direct VPS37A evidence concerns ESCRT recruitment to phagophores and autophagosome completion, which is better captured as GO:0000045 autophagosome assembly. Proposed replacements: autophagosome assembly Supporting Evidence: PMID:31519728 the ESCRT-I subunit VPS37A as a critical component for phagophore closure PMID:31519728 VPS37A localizes on the phagophore PMID:31519728 required for autophagosome completion but dispensable for ESCRT-I complex formation PMID:31519728 loss of VPS37A abrogates the phagophore recruitment PMID:32424346 ESCRT-I helical interface is required for autophagosome closure
GO:0006623 protein targeting to vacuole	IBA GO_REF:0000033	MODIFY	Summary: Protein targeting to vacuole is too broad for the VPS37A endosomal sorting evidence. Reason: The supported process is ubiquitin-dependent MVB sorting and lysosomal routing of endocytic cargo, not generic protein targeting to vacuole. Proposed replacements: ubiquitin-dependent protein catabolic process via the multivesicular body sorting pathway protein transport to vacuole involved in ubiquitin-dependent protein catabolic process via the multivesicular body sorting pathway Supporting Evidence: file:human/VPS37A/VPS37A-uniprot.txt Required for the sorting of endocytic file:human/VPS37A/VPS37A-uniprot.txt ubiquitinated cargos into multivesicular bodies PMID:15240819 retards epidermal growth factor (EGF) receptor degradation PMID:15240819 essential for lysosomal sorting of EGF receptors PMID:21757351 required for sorting EGFR to the MVB
GO:0000813 ESCRT I complex	IEA GO_REF:0000117	ACCEPT	Summary: ESCRT-I complex membership is the central VPS37A cellular-component annotation. Reason: VPS37A is the VPS37-family ESCRT-I subunit in TSG101-VPS28-VPS37-MVB12/UBAP variant complexes. Supporting Evidence: file:human/VPS37A/VPS37A-uniprot.txt Component of the ESCRT-I complex file:human/VPS37A/VPS37A-uniprot.txt which consists of TSG101, VPS28, a VPS37 file:human/VPS37A/VPS37A-uniprot.txt Interacts with TSG101, VPS28 and HGS PMID:15240819 a subunit of mammalian ESCRT-I PMID:21757351 Mammalian ESCRT-I comprises TSG101, VPS28, VPS37A-D, and MVB12A/B
GO:0005634 nucleus	IEA GO_REF:0000044	KEEP AS NON CORE	Summary: nucleus is supported as a secondary context but is not the core VPS37A proteostasis function. Reason: Viral budding and nuclear/nucleoplasm localizations are secondary observations or contexts; the core function is ESCRT-I endosomal sorting and phagophore closure. Supporting Evidence: PMID:18005716 plays essential roles in HIV budding and endosomal protein sorting PMID:20588296 viral budding, cytokinesis and, probably, autophagy file:human/VPS37A/VPS37A-uniprot.txt Nucleus
GO:0016236 macroautophagy	IEA GO_REF:0000117	MODIFY	Summary: Macroautophagy is too broad for the directly tested VPS37A role. Reason: VPS37A is directly required for phagophore closure/autophagosome completion, so GO:0000045 autophagosome assembly is the more precise term. Proposed replacements: autophagosome assembly Supporting Evidence: PMID:31519728 the ESCRT-I subunit VPS37A as a critical component for phagophore closure PMID:31519728 VPS37A localizes on the phagophore PMID:31519728 required for autophagosome completion but dispensable for ESCRT-I complex formation PMID:31519728 loss of VPS37A abrogates the phagophore recruitment PMID:32424346 ESCRT-I helical interface is required for autophagosome closure
GO:0031902 late endosome membrane	IEA GO_REF:0000044	ACCEPT	Summary: late endosome membrane localization is supported and relevant to VPS37A/ESCRT-I function. Reason: VPS37A is a peripheral late-endosome/endosome-membrane ESCRT-I component and colocalizes with hVps28 on LAMP1-positive endosomes. Supporting Evidence: file:human/VPS37A/VPS37A-uniprot.txt Late endosome membrane PMID:15240819 colocalizes with hVps28 on LAMP1-positive endosomes
GO:0036258 multivesicular body assembly	IEA GO_REF:0000117	ACCEPT	Summary: multivesicular body assembly is supported as part of the core VPS37A/ESCRT-I endosomal cargo-sorting role. Reason: VPS37A is required for ESCRT-I-dependent sorting of ubiquitinated endocytic cargos, including EGFR, into MVB/lysosomal routes. Supporting Evidence: file:human/VPS37A/VPS37A-uniprot.txt Required for the sorting of endocytic file:human/VPS37A/VPS37A-uniprot.txt ubiquitinated cargos into multivesicular bodies PMID:15240819 retards epidermal growth factor (EGF) receptor degradation PMID:15240819 essential for lysosomal sorting of EGF receptors PMID:21757351 required for sorting EGFR to the MVB
GO:0039702 viral budding via host ESCRT complex	IEA GO_REF:0000117	KEEP AS NON CORE	Summary: viral budding via host ESCRT complex is supported as a secondary context but is not the core VPS37A proteostasis function. Reason: Viral budding and nuclear/nucleoplasm localizations are secondary observations or contexts; the core function is ESCRT-I endosomal sorting and phagophore closure. Supporting Evidence: PMID:18005716 plays essential roles in HIV budding and endosomal protein sorting PMID:20588296 viral budding, cytokinesis and, probably, autophagy file:human/VPS37A/VPS37A-uniprot.txt Nucleus
GO:0005515 protein binding	IPI PMID:25416956 A proteome-scale map of the human interactome network.	MARK AS OVER ANNOTATED	Summary: Protein binding is too generic to represent VPS37A function. Reason: The informative biology is ESCRT-I complex membership, endosomal MVB sorting, and phagophore-closure recruitment, not generic protein binding from interaction assays. Proposed replacements: ESCRT I complex ubiquitin-dependent protein catabolic process via the multivesicular body sorting pathway Supporting Evidence: file:human/VPS37A/VPS37A-uniprot.txt Component of the ESCRT-I complex file:human/VPS37A/VPS37A-uniprot.txt which consists of TSG101, VPS28, a VPS37 file:human/VPS37A/VPS37A-uniprot.txt Interacts with TSG101, VPS28 and HGS PMID:15240819 a subunit of mammalian ESCRT-I PMID:21757351 Mammalian ESCRT-I comprises TSG101, VPS28, VPS37A-D, and MVB12A/B file:human/VPS37A/VPS37A-uniprot.txt Required for the sorting of endocytic file:human/VPS37A/VPS37A-uniprot.txt ubiquitinated cargos into multivesicular bodies PMID:15240819 retards epidermal growth factor (EGF) receptor degradation PMID:15240819 essential for lysosomal sorting of EGF receptors PMID:21757351 required for sorting EGFR to the MVB
GO:0005515 protein binding	IPI PMID:32296183 A reference map of the human binary protein interactome.	MARK AS OVER ANNOTATED	Summary: Protein binding is too generic to represent VPS37A function. Reason: The informative biology is ESCRT-I complex membership, endosomal MVB sorting, and phagophore-closure recruitment, not generic protein binding from interaction assays. Proposed replacements: ESCRT I complex ubiquitin-dependent protein catabolic process via the multivesicular body sorting pathway Supporting Evidence: file:human/VPS37A/VPS37A-uniprot.txt Component of the ESCRT-I complex file:human/VPS37A/VPS37A-uniprot.txt which consists of TSG101, VPS28, a VPS37 file:human/VPS37A/VPS37A-uniprot.txt Interacts with TSG101, VPS28 and HGS PMID:15240819 a subunit of mammalian ESCRT-I PMID:21757351 Mammalian ESCRT-I comprises TSG101, VPS28, VPS37A-D, and MVB12A/B file:human/VPS37A/VPS37A-uniprot.txt Required for the sorting of endocytic file:human/VPS37A/VPS37A-uniprot.txt ubiquitinated cargos into multivesicular bodies PMID:15240819 retards epidermal growth factor (EGF) receptor degradation PMID:15240819 essential for lysosomal sorting of EGF receptors PMID:21757351 required for sorting EGFR to the MVB
GO:0005515 protein binding	IPI PMID:32814053 Interactome Mapping Provides a Network of Neurodegenerative ...	MARK AS OVER ANNOTATED	Summary: Protein binding is too generic to represent VPS37A function. Reason: The informative biology is ESCRT-I complex membership, endosomal MVB sorting, and phagophore-closure recruitment, not generic protein binding from interaction assays. Proposed replacements: ESCRT I complex ubiquitin-dependent protein catabolic process via the multivesicular body sorting pathway Supporting Evidence: file:human/VPS37A/VPS37A-uniprot.txt Component of the ESCRT-I complex file:human/VPS37A/VPS37A-uniprot.txt which consists of TSG101, VPS28, a VPS37 file:human/VPS37A/VPS37A-uniprot.txt Interacts with TSG101, VPS28 and HGS PMID:15240819 a subunit of mammalian ESCRT-I PMID:21757351 Mammalian ESCRT-I comprises TSG101, VPS28, VPS37A-D, and MVB12A/B file:human/VPS37A/VPS37A-uniprot.txt Required for the sorting of endocytic file:human/VPS37A/VPS37A-uniprot.txt ubiquitinated cargos into multivesicular bodies PMID:15240819 retards epidermal growth factor (EGF) receptor degradation PMID:15240819 essential for lysosomal sorting of EGF receptors PMID:21757351 required for sorting EGFR to the MVB
GO:0005515 protein binding	IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling...	MARK AS OVER ANNOTATED	Summary: Protein binding is too generic to represent VPS37A function. Reason: The informative biology is ESCRT-I complex membership, endosomal MVB sorting, and phagophore-closure recruitment, not generic protein binding from interaction assays. Proposed replacements: ESCRT I complex ubiquitin-dependent protein catabolic process via the multivesicular body sorting pathway Supporting Evidence: file:human/VPS37A/VPS37A-uniprot.txt Component of the ESCRT-I complex file:human/VPS37A/VPS37A-uniprot.txt which consists of TSG101, VPS28, a VPS37 file:human/VPS37A/VPS37A-uniprot.txt Interacts with TSG101, VPS28 and HGS PMID:15240819 a subunit of mammalian ESCRT-I PMID:21757351 Mammalian ESCRT-I comprises TSG101, VPS28, VPS37A-D, and MVB12A/B file:human/VPS37A/VPS37A-uniprot.txt Required for the sorting of endocytic file:human/VPS37A/VPS37A-uniprot.txt ubiquitinated cargos into multivesicular bodies PMID:15240819 retards epidermal growth factor (EGF) receptor degradation PMID:15240819 essential for lysosomal sorting of EGF receptors PMID:21757351 required for sorting EGFR to the MVB
GO:0005515 protein binding	IPI PMID:35271311 OpenCell: Endogenous tagging for the cartography of human ce...	MARK AS OVER ANNOTATED	Summary: Protein binding is too generic to represent VPS37A function. Reason: The informative biology is ESCRT-I complex membership, endosomal MVB sorting, and phagophore-closure recruitment, not generic protein binding from interaction assays. Proposed replacements: ESCRT I complex ubiquitin-dependent protein catabolic process via the multivesicular body sorting pathway Supporting Evidence: file:human/VPS37A/VPS37A-uniprot.txt Component of the ESCRT-I complex file:human/VPS37A/VPS37A-uniprot.txt which consists of TSG101, VPS28, a VPS37 file:human/VPS37A/VPS37A-uniprot.txt Interacts with TSG101, VPS28 and HGS PMID:15240819 a subunit of mammalian ESCRT-I PMID:21757351 Mammalian ESCRT-I comprises TSG101, VPS28, VPS37A-D, and MVB12A/B file:human/VPS37A/VPS37A-uniprot.txt Required for the sorting of endocytic file:human/VPS37A/VPS37A-uniprot.txt ubiquitinated cargos into multivesicular bodies PMID:15240819 retards epidermal growth factor (EGF) receptor degradation PMID:15240819 essential for lysosomal sorting of EGF receptors PMID:21757351 required for sorting EGFR to the MVB
GO:0005654 nucleoplasm	IDA GO_REF:0000052	KEEP AS NON CORE	Summary: nucleoplasm is supported as a secondary context but is not the core VPS37A proteostasis function. Reason: Viral budding and nuclear/nucleoplasm localizations are secondary observations or contexts; the core function is ESCRT-I endosomal sorting and phagophore closure. Supporting Evidence: PMID:18005716 plays essential roles in HIV budding and endosomal protein sorting PMID:20588296 viral budding, cytokinesis and, probably, autophagy file:human/VPS37A/VPS37A-uniprot.txt Nucleus
GO:0010008 endosome membrane	NAS PMID:32424346 A helical assembly of human ESCRT-I scaffolds reverse-topolo...	ACCEPT	Summary: endosome membrane localization is supported and relevant to VPS37A/ESCRT-I function. Reason: VPS37A is a peripheral late-endosome/endosome-membrane ESCRT-I component and colocalizes with hVps28 on LAMP1-positive endosomes. Supporting Evidence: file:human/VPS37A/VPS37A-uniprot.txt Late endosome membrane PMID:15240819 colocalizes with hVps28 on LAMP1-positive endosomes
GO:0036258 multivesicular body assembly	NAS PMID:32424346 A helical assembly of human ESCRT-I scaffolds reverse-topolo...	ACCEPT	Summary: multivesicular body assembly is supported as part of the core VPS37A/ESCRT-I endosomal cargo-sorting role. Reason: VPS37A is required for ESCRT-I-dependent sorting of ubiquitinated endocytic cargos, including EGFR, into MVB/lysosomal routes. Supporting Evidence: file:human/VPS37A/VPS37A-uniprot.txt Required for the sorting of endocytic file:human/VPS37A/VPS37A-uniprot.txt ubiquitinated cargos into multivesicular bodies PMID:15240819 retards epidermal growth factor (EGF) receptor degradation PMID:15240819 essential for lysosomal sorting of EGF receptors PMID:21757351 required for sorting EGFR to the MVB
GO:0043328 protein transport to vacuole involved in ubiquitin-dependent protein catabolic process via the multivesicular body sorting pathway	NAS PMID:32424346 A helical assembly of human ESCRT-I scaffolds reverse-topolo...	ACCEPT	Summary: protein transport to vacuole involved in ubiquitin-dependent protein catabolic process via the multivesicular body sorting pathway is supported as part of the core VPS37A/ESCRT-I endosomal cargo-sorting role. Reason: VPS37A is required for ESCRT-I-dependent sorting of ubiquitinated endocytic cargos, including EGFR, into MVB/lysosomal routes. Supporting Evidence: file:human/VPS37A/VPS37A-uniprot.txt Required for the sorting of endocytic file:human/VPS37A/VPS37A-uniprot.txt ubiquitinated cargos into multivesicular bodies PMID:15240819 retards epidermal growth factor (EGF) receptor degradation PMID:15240819 essential for lysosomal sorting of EGF receptors PMID:21757351 required for sorting EGFR to the MVB
GO:0090148 membrane fission	NAS PMID:32424346 A helical assembly of human ESCRT-I scaffolds reverse-topolo...	ACCEPT	Summary: Membrane fission is supported for ESCRT-I reverse-topology membrane remodeling. Reason: VPS37A is a core ESCRT-I component; ESCRT-I scaffolds upstream ESCRT recruitment for reverse-topology membrane remodeling, including phagophore closure. Supporting Evidence: PMID:20588296 ESCRT-I and ESCRT-II direct membrane budding away from the cytosol PMID:31519728 VPS37A coordinates the recruitment of a unique set of ESCRT machinery components for phagophore closure PMID:32424346 A helical assembly of human ESCRT-I scaffolds reverse-topology membrane scission
GO:0000813 ESCRT I complex	IPI PMID:18005716 Identification of human MVB12 proteins as ESCRT-I subunits t...	ACCEPT	Summary: ESCRT-I complex membership is the central VPS37A cellular-component annotation. Reason: VPS37A is the VPS37-family ESCRT-I subunit in TSG101-VPS28-VPS37-MVB12/UBAP variant complexes. Supporting Evidence: file:human/VPS37A/VPS37A-uniprot.txt Component of the ESCRT-I complex file:human/VPS37A/VPS37A-uniprot.txt which consists of TSG101, VPS28, a VPS37 file:human/VPS37A/VPS37A-uniprot.txt Interacts with TSG101, VPS28 and HGS PMID:15240819 a subunit of mammalian ESCRT-I PMID:21757351 Mammalian ESCRT-I comprises TSG101, VPS28, VPS37A-D, and MVB12A/B
GO:0000813 ESCRT I complex	IPI PMID:21757351 UBAP1 is a component of an endosome-specific ESCRT-I complex...	ACCEPT	Summary: ESCRT-I complex membership is the central VPS37A cellular-component annotation. Reason: VPS37A is the VPS37-family ESCRT-I subunit in TSG101-VPS28-VPS37-MVB12/UBAP variant complexes. Supporting Evidence: file:human/VPS37A/VPS37A-uniprot.txt Component of the ESCRT-I complex file:human/VPS37A/VPS37A-uniprot.txt which consists of TSG101, VPS28, a VPS37 file:human/VPS37A/VPS37A-uniprot.txt Interacts with TSG101, VPS28 and HGS PMID:15240819 a subunit of mammalian ESCRT-I PMID:21757351 Mammalian ESCRT-I comprises TSG101, VPS28, VPS37A-D, and MVB12A/B
GO:0016236 macroautophagy	TAS PMID:20588296 Membrane budding and scission by the ESCRT machinery: it's a...	MODIFY	Summary: Macroautophagy is too broad for the directly tested VPS37A role. Reason: VPS37A is directly required for phagophore closure/autophagosome completion, so GO:0000045 autophagosome assembly is the more precise term. Proposed replacements: autophagosome assembly Supporting Evidence: PMID:31519728 the ESCRT-I subunit VPS37A as a critical component for phagophore closure PMID:31519728 VPS37A localizes on the phagophore PMID:31519728 required for autophagosome completion but dispensable for ESCRT-I complex formation PMID:31519728 loss of VPS37A abrogates the phagophore recruitment PMID:32424346 ESCRT-I helical interface is required for autophagosome closure
GO:0000813 ESCRT I complex	TAS PMID:20588296 Membrane budding and scission by the ESCRT machinery: it's a...	ACCEPT	Summary: ESCRT-I complex membership is the central VPS37A cellular-component annotation. Reason: VPS37A is the VPS37-family ESCRT-I subunit in TSG101-VPS28-VPS37-MVB12/UBAP variant complexes. Supporting Evidence: file:human/VPS37A/VPS37A-uniprot.txt Component of the ESCRT-I complex file:human/VPS37A/VPS37A-uniprot.txt which consists of TSG101, VPS28, a VPS37 file:human/VPS37A/VPS37A-uniprot.txt Interacts with TSG101, VPS28 and HGS PMID:15240819 a subunit of mammalian ESCRT-I PMID:21757351 Mammalian ESCRT-I comprises TSG101, VPS28, VPS37A-D, and MVB12A/B
GO:0036258 multivesicular body assembly	TAS PMID:20588296 Membrane budding and scission by the ESCRT machinery: it's a...	ACCEPT	Summary: multivesicular body assembly is supported as part of the core VPS37A/ESCRT-I endosomal cargo-sorting role. Reason: VPS37A is required for ESCRT-I-dependent sorting of ubiquitinated endocytic cargos, including EGFR, into MVB/lysosomal routes. Supporting Evidence: file:human/VPS37A/VPS37A-uniprot.txt Required for the sorting of endocytic file:human/VPS37A/VPS37A-uniprot.txt ubiquitinated cargos into multivesicular bodies PMID:15240819 retards epidermal growth factor (EGF) receptor degradation PMID:15240819 essential for lysosomal sorting of EGF receptors PMID:21757351 required for sorting EGFR to the MVB
GO:0039702 viral budding via host ESCRT complex	TAS PMID:20588296 Membrane budding and scission by the ESCRT machinery: it's a...	KEEP AS NON CORE	Summary: viral budding via host ESCRT complex is supported as a secondary context but is not the core VPS37A proteostasis function. Reason: Viral budding and nuclear/nucleoplasm localizations are secondary observations or contexts; the core function is ESCRT-I endosomal sorting and phagophore closure. Supporting Evidence: PMID:18005716 plays essential roles in HIV budding and endosomal protein sorting PMID:20588296 viral budding, cytokinesis and, probably, autophagy file:human/VPS37A/VPS37A-uniprot.txt Nucleus
GO:0000813 ESCRT I complex	IDA PMID:18005716 Identification of human MVB12 proteins as ESCRT-I subunits t...	ACCEPT	Summary: ESCRT-I complex membership is the central VPS37A cellular-component annotation. Reason: VPS37A is the VPS37-family ESCRT-I subunit in TSG101-VPS28-VPS37-MVB12/UBAP variant complexes. Supporting Evidence: file:human/VPS37A/VPS37A-uniprot.txt Component of the ESCRT-I complex file:human/VPS37A/VPS37A-uniprot.txt which consists of TSG101, VPS28, a VPS37 file:human/VPS37A/VPS37A-uniprot.txt Interacts with TSG101, VPS28 and HGS PMID:15240819 a subunit of mammalian ESCRT-I PMID:21757351 Mammalian ESCRT-I comprises TSG101, VPS28, VPS37A-D, and MVB12A/B
GO:0000813 ESCRT I complex	IDA PMID:20654576 Distinct functions of human MVB12A and MVB12B in the ESCRT-I...	ACCEPT	Summary: ESCRT-I complex membership is the central VPS37A cellular-component annotation. Reason: VPS37A is the VPS37-family ESCRT-I subunit in TSG101-VPS28-VPS37-MVB12/UBAP variant complexes. Supporting Evidence: file:human/VPS37A/VPS37A-uniprot.txt Component of the ESCRT-I complex file:human/VPS37A/VPS37A-uniprot.txt which consists of TSG101, VPS28, a VPS37 file:human/VPS37A/VPS37A-uniprot.txt Interacts with TSG101, VPS28 and HGS PMID:15240819 a subunit of mammalian ESCRT-I PMID:21757351 Mammalian ESCRT-I comprises TSG101, VPS28, VPS37A-D, and MVB12A/B
GO:0043162 ubiquitin-dependent protein catabolic process via the multivesicular body sorting pathway	IC PMID:20654576 Distinct functions of human MVB12A and MVB12B in the ESCRT-I...	ACCEPT	Summary: ubiquitin-dependent protein catabolic process via the multivesicular body sorting pathway is supported as part of the core VPS37A/ESCRT-I endosomal cargo-sorting role. Reason: VPS37A is required for ESCRT-I-dependent sorting of ubiquitinated endocytic cargos, including EGFR, into MVB/lysosomal routes. Supporting Evidence: file:human/VPS37A/VPS37A-uniprot.txt Required for the sorting of endocytic file:human/VPS37A/VPS37A-uniprot.txt ubiquitinated cargos into multivesicular bodies PMID:15240819 retards epidermal growth factor (EGF) receptor degradation PMID:15240819 essential for lysosomal sorting of EGF receptors PMID:21757351 required for sorting EGFR to the MVB
GO:0000813 ESCRT I complex	IDA PMID:21757351 UBAP1 is a component of an endosome-specific ESCRT-I complex...	ACCEPT	Summary: ESCRT-I complex membership is the central VPS37A cellular-component annotation. Reason: VPS37A is the VPS37-family ESCRT-I subunit in TSG101-VPS28-VPS37-MVB12/UBAP variant complexes. Supporting Evidence: file:human/VPS37A/VPS37A-uniprot.txt Component of the ESCRT-I complex file:human/VPS37A/VPS37A-uniprot.txt which consists of TSG101, VPS28, a VPS37 file:human/VPS37A/VPS37A-uniprot.txt Interacts with TSG101, VPS28 and HGS PMID:15240819 a subunit of mammalian ESCRT-I PMID:21757351 Mammalian ESCRT-I comprises TSG101, VPS28, VPS37A-D, and MVB12A/B
GO:0043162 ubiquitin-dependent protein catabolic process via the multivesicular body sorting pathway	IMP PMID:21757351 UBAP1 is a component of an endosome-specific ESCRT-I complex...	ACCEPT	Summary: ubiquitin-dependent protein catabolic process via the multivesicular body sorting pathway is supported as part of the core VPS37A/ESCRT-I endosomal cargo-sorting role. Reason: VPS37A is required for ESCRT-I-dependent sorting of ubiquitinated endocytic cargos, including EGFR, into MVB/lysosomal routes. Supporting Evidence: file:human/VPS37A/VPS37A-uniprot.txt Required for the sorting of endocytic file:human/VPS37A/VPS37A-uniprot.txt ubiquitinated cargos into multivesicular bodies PMID:15240819 retards epidermal growth factor (EGF) receptor degradation PMID:15240819 essential for lysosomal sorting of EGF receptors PMID:21757351 required for sorting EGFR to the MVB
GO:0010008 endosome membrane	TAS Reactome:R-HSA-184269	ACCEPT	Summary: endosome membrane localization is supported and relevant to VPS37A/ESCRT-I function. Reason: VPS37A is a peripheral late-endosome/endosome-membrane ESCRT-I component and colocalizes with hVps28 on LAMP1-positive endosomes. Supporting Evidence: file:human/VPS37A/VPS37A-uniprot.txt Late endosome membrane PMID:15240819 colocalizes with hVps28 on LAMP1-positive endosomes
GO:0010008 endosome membrane	TAS Reactome:R-HSA-3149434	ACCEPT	Summary: endosome membrane localization is supported and relevant to VPS37A/ESCRT-I function. Reason: VPS37A is a peripheral late-endosome/endosome-membrane ESCRT-I component and colocalizes with hVps28 on LAMP1-positive endosomes. Supporting Evidence: file:human/VPS37A/VPS37A-uniprot.txt Late endosome membrane PMID:15240819 colocalizes with hVps28 on LAMP1-positive endosomes
GO:0010008 endosome membrane	TAS Reactome:R-HSA-3159232	ACCEPT	Summary: endosome membrane localization is supported and relevant to VPS37A/ESCRT-I function. Reason: VPS37A is a peripheral late-endosome/endosome-membrane ESCRT-I component and colocalizes with hVps28 on LAMP1-positive endosomes. Supporting Evidence: file:human/VPS37A/VPS37A-uniprot.txt Late endosome membrane PMID:15240819 colocalizes with hVps28 on LAMP1-positive endosomes
GO:0010008 endosome membrane	TAS Reactome:R-HSA-917696	ACCEPT	Summary: endosome membrane localization is supported and relevant to VPS37A/ESCRT-I function. Reason: VPS37A is a peripheral late-endosome/endosome-membrane ESCRT-I component and colocalizes with hVps28 on LAMP1-positive endosomes. Supporting Evidence: file:human/VPS37A/VPS37A-uniprot.txt Late endosome membrane PMID:15240819 colocalizes with hVps28 on LAMP1-positive endosomes
GO:0010008 endosome membrane	TAS Reactome:R-HSA-917730	ACCEPT	Summary: endosome membrane localization is supported and relevant to VPS37A/ESCRT-I function. Reason: VPS37A is a peripheral late-endosome/endosome-membrane ESCRT-I component and colocalizes with hVps28 on LAMP1-positive endosomes. Supporting Evidence: file:human/VPS37A/VPS37A-uniprot.txt Late endosome membrane PMID:15240819 colocalizes with hVps28 on LAMP1-positive endosomes
GO:0000045 autophagosome assembly	IMP PMID:31519728 VPS37A directs ESCRT recruitment for phagophore closure.	NEW	Summary: VPS37A should be annotated to autophagosome assembly for its direct phagophore-closure role. Reason: VPS37A is directly identified as an ESCRT-I component required for phagophore closure/autophagosome completion, and loss of VPS37A blocks recruitment of VPS28 and CHMP2A. Supporting Evidence: PMID:31519728 the ESCRT-I subunit VPS37A as a critical component for phagophore closure PMID:31519728 VPS37A localizes on the phagophore PMID:31519728 required for autophagosome completion but dispensable for ESCRT-I complex formation PMID:31519728 loss of VPS37A abrogates the phagophore recruitment PMID:32424346 ESCRT-I helical interface is required for autophagosome closure

Core Functions

VPS37A is an ESCRT-I subunit that organizes endosomal MVB cargo sorting and, through its PUEV-containing phagophore-targeting function, coordinates recruitment of VPS28 and ESCRT-III machinery for autophagosome completion.

Directly Involved In:

ubiquitin-dependent protein catabolic process via the multivesicular body sorting pathway multivesicular body assembly membrane fission autophagosome assembly

Cellular Locations:

endosome membrane late endosome membrane

In Complex:

ESCRT I complex

Supporting Evidence:

file:human/VPS37A/VPS37A-uniprot.txt
Component of the ESCRT-I complex
file:human/VPS37A/VPS37A-uniprot.txt
which consists of TSG101, VPS28, a VPS37
file:human/VPS37A/VPS37A-uniprot.txt
Interacts with TSG101, VPS28 and HGS
PMID:15240819
a subunit of mammalian ESCRT-I
PMID:21757351
Mammalian ESCRT-I comprises TSG101, VPS28, VPS37A-D, and MVB12A/B
file:human/VPS37A/VPS37A-uniprot.txt
Required for the sorting of endocytic
file:human/VPS37A/VPS37A-uniprot.txt
ubiquitinated cargos into multivesicular bodies
PMID:15240819
retards epidermal growth factor (EGF) receptor degradation
PMID:15240819
essential for lysosomal sorting of EGF receptors
PMID:21757351
required for sorting EGFR to the MVB
file:human/VPS37A/VPS37A-uniprot.txt
Late endosome membrane
PMID:15240819
colocalizes with hVps28 on LAMP1-positive endosomes
PMID:31519728
the ESCRT-I subunit VPS37A as a critical component for phagophore closure
PMID:31519728
VPS37A localizes on the phagophore
PMID:31519728
required for autophagosome completion but dispensable for ESCRT-I complex formation
PMID:31519728
loss of VPS37A abrogates the phagophore recruitment
PMID:32424346
ESCRT-I helical interface is required for autophagosome closure

References

GO_REF:0000033

Annotation inferences using phylogenetic trees

GO_REF:0000044

Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular Location vocabulary mapping, accompanied by conservative changes to GO terms applied by UniProt

GO_REF:0000052

Gene Ontology annotation based on curation of immunofluorescence data

GO_REF:0000117

Electronic Gene Ontology annotations created by ARBA machine learning models

PMID:18005716

Identification of human MVB12 proteins as ESCRT-I subunits that function in HIV budding.

PMID:20588296

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

PMID:20654576

Distinct functions of human MVB12A and MVB12B in the ESCRT-I dependent on their posttranslational modifications.

PMID:21757351

UBAP1 is a component of an endosome-specific ESCRT-I complex that is essential for MVB sorting.

PMID:25416956

A proteome-scale map of the human interactome network.

PMID:32296183

A reference map of the human binary protein interactome.

PMID:32424346

A helical assembly of human ESCRT-I scaffolds reverse-topology membrane scission.

PMID:32814053

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

PMID:33961781

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

PMID:35271311

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

Reactome:R-HSA-184269

Monoubiquitinated N-myristoyl GAG polyprotein is targeted to the late endosomal vesicle membrane by the ESCRT-I complex

Reactome:R-HSA-3149434

Transport of GAG to the Plasma Membrane

Reactome:R-HSA-3159232

Recruitment Of HIV Virion Budding Machinery

Reactome:R-HSA-917696

Cargo Sequestration

Reactome:R-HSA-917730

Cargo Recognition And Sorting

PMID:15240819

The growth-regulatory protein HCRP1/hVps37A is a subunit of mammalian ESCRT-I and mediates receptor down-regulation.

PMID:31519728

VPS37A directs ESCRT recruitment for phagophore closure.

file:human/VPS37A/VPS37A-uniprot.txt

UniProtKB record for human VPS37A

file:human/VPS37A/VPS37A-notes.md

VPS37A review notes

Suggested Experiments

Experiment: Use endogenous VPS37A knockout/rescue with PUEV-containing and PUEV-lacking isoforms, then assay HT-LC3 closure, VPS28/CHMP2A recruitment, and EGFR degradation in parallel.

Hypothesis: PUEV-containing VPS37A isoforms are specifically required for phagophore closure, while the ESCRT-I Mod(r) assembly domain remains sufficient for EGFR MVB sorting.

Type: VPS37A isoform and PUEV-domain rescue

📚 Additional Documentation

Notes

(VPS37A-notes.md)

VPS37A review notes

Scope

VPS37A is reviewed in the PN autophagophore sealing branch as an ESCRT-I component. PN entries without PMIDs were used as context only. Unlike VPS28, VPS37A has direct mammalian phagophore-closure evidence: the VPS37A PUEV-containing isoform recruits ESCRT machinery to phagophores and is required for autophagosome completion.

Evidence synthesis

VPS37A is a core ESCRT-I subunit. UniProt describes it as a "Component of the ESCRT-I complex" and says it is "Required for the sorting of endocytic ubiquitinated cargos into multivesicular bodies" [file:human/VPS37A/VPS37A-uniprot.txt, "Component of the ESCRT-I complex"; file:human/VPS37A/VPS37A-uniprot.txt, "Required for the sorting of endocytic ubiquitinated cargos into multivesicular bodies"]. UniProt also states that ESCRT-I consists of "TSG101, VPS28, a VPS37 protein" and that VPS37A interacts with TSG101, VPS28, and HGS [file:human/VPS37A/VPS37A-uniprot.txt, "which consists of TSG101, VPS28, a VPS37"; file:human/VPS37A/VPS37A-uniprot.txt, "Interacts with TSG101, VPS28 and HGS"]. These lines support ESCRT-I complex membership and MVB/endosomal cargo-sorting annotations.

The original HCRP1/hVps37A study supports the endosomal sorting role. Its abstract reports that HCRP1/hVps37A "interacts with Tsg101, hVps28, and their upstream regulator Hrs", "cofractionates with Tsg101 and hVps28", "colocalizes with hVps28 on LAMP1-positive endosomes", and that HCRP1 depletion "retards epidermal growth factor (EGF) receptor degradation" [PMID:15240819, "interacts with Tsg101, hVps28, and their upstream regulator Hrs"; PMID:15240819, "cofractionates with Tsg101 and hVps28"; PMID:15240819, "colocalizes with hVps28 on LAMP1-positive endosomes"; PMID:15240819, "retards epidermal growth factor (EGF) receptor degradation"]. The same abstract concludes that HCRP1 is "a subunit of mammalian ESCRT-I" and that its function is "essential for lysosomal sorting of EGF receptors" [PMID:15240819, "a subunit of mammalian ESCRT-I"; PMID:15240819, "essential for lysosomal sorting of EGF receptors"].

The PN-specific autophagy term should be autophagosome assembly/phagophore closure rather than broad macroautophagy. The phagophore closure paper identifies "the ESCRT-I subunit VPS37A as a critical component for phagophore closure", shows that VPS37A localizes on the phagophore through its N-terminal PUEV domain, and says this domain is "required for autophagosome completion but dispensable for ESCRT-I complex formation" [PMID:31519728, "the ESCRT-I subunit VPS37A as a critical component for phagophore closure"; PMID:31519728, "VPS37A localizes on the phagophore"; PMID:31519728, "required for autophagosome completion but dispensable for ESCRT-I complex formation"]. It also reports that loss of VPS37A abrogates phagophore recruitment of VPS28 and CHMP2A and that VPS37A coordinates ESCRT machinery for phagophore closure [PMID:31519728, "loss of VPS37A abrogates the phagophore recruitment"; PMID:31519728, "VPS37A coordinates the recruitment of a unique set of ESCRT machinery components for phagophore closure"].

Protein binding rows should not be accepted as informative molecular functions. They should be marked over-annotated in favor of ESCRT-I complex membership, MVB sorting, and autophagosome assembly. Viral budding rows are supported ESCRT contexts but are non-core for the proteostasis review. Nuclear/nucleoplasm rows are supported in UniProt as localization observations but should be non-core relative to ESCRT-I endosomal and phagophore functions.

Falcon

Falcon deep research was started for VPS37A on 2026-06-02 but timed out after 600 seconds and did not produce a usable report. The review therefore relies on UniProt, cached primary literature, and PN context rather than Falcon output.

Description cleanup note

The YAML description field was revised to keep it as a standalone biological summary. Project-specific curation framing moved here instead.

Moved out of the YAML description: the prior wording described VPS37A's phagophore-closure role as PN-relevant.

Pn Notes

(VPS37A-pn-notes.md)

VPS37A PN Consistency Notes

Generated: 2026-06-18
Project: PROTEOSTASIS
Scope: PN consistency rereview against local AIGR review and available deep-research artifacts
UniProt: Q8NEZ2
AIGR review status: COMPLETE
Review batch: proteostasis-pr-1217 (PR 1217)
Batch change status: added

Source Files Checked

AIGR review YAML: present - genes/human/VPS37A/VPS37A-ai-review.yaml
AIGR review HTML: present - genes/human/VPS37A/VPS37A-ai-review.html
Gene notes: present - genes/human/VPS37A/VPS37A-notes.md
GOA TSV: present - genes/human/VPS37A/VPS37A-goa.tsv
UniProt record: present - genes/human/VPS37A/VPS37A-uniprot.txt
PN dossier: projects/PROTEOSTASIS/reports/phase1_dossiers/VPS37A.md
PN consistency section: projects/PROTEOSTASIS/reports/phase1_dossiers/_sections/VPS37A.md
PN projection report: projects/PROTEOSTASIS/reports/pn_projection/pn_projected_gene_go_summary.tsv
PN mapping audit: projects/PROTEOSTASIS/reports/pn_mapping_audit/current_mapping_scrutiny.tsv

Deep Research Files

No *-deep-research*.md file found in this gene directory.

AIGR Review Snapshot

Description: VPS37A is a VPS37-family ESCRT-I subunit that complexes with TSG101, VPS28, and MVB12/UBAP-family subunits. It supports ubiquitin-dependent endosomal cargo sorting into multivesicular bodies and has a directly tested role in phagophore closure, where its PUEV-containing N terminus recruits ESCRT machinery for autophagosome completion.
Existing/core annotation action counts: ACCEPT: 23; KEEP_AS_NON_CORE: 4; MARK_AS_OVER_ANNOTATED: 5; MODIFY: 4; NEW: 1

PN Consistency Summary

Consistency: Strongly consistent. VPS37A is the one VPS37 paralog with direct mammalian phagophore-closure evidence (PMID:31519728), and the review uniquely adds GO:0000045 as a NEW annotation (plus MODIFY of GO:0006612/GO:0016236→GO:0000045). PN's two projections (GO:0000813 ESCRT-I; GO:0000045 autophagosome assembly) match the review exactly. The UEV/UPS placement aligns with ESCRT-I/ubiquitin cargo sorting (review accepts GO:0043162, GO:0036258, GO:0000813).
PN story / NEW pressure: Already captured. PN asserts phagophore sealing → the review independently makes GO:0000045 a NEW term (verified real via OLS) supported by VPS37A-on-phagophore + VPS28/CHMP2A recruitment evidence. No additional new term warranted; PN adds nothing the review lacks.
Evidence alignment: Strong overlap. PN cites the ESCRT-I scaffold paper (=PMID:32424346) and "VPS37A directs ESCRT recruitment for phagophore closure" (=PMID:31519728), both load-bearing in the review. PN's MDPI "Key Regulators of Autophagosome Closure" review is not cited; the review uses primary literature instead.
Verdict: Fully consistent; PN projections match the review's accepted/NEW terms. No edits needed.

Full Consistency Review

UniProt: Q8NEZ2 · batch: proteostasis-pr-1217 · review status: COMPLETE
PN placement: 3 rows, ALP+UPS — (1) ALP Autophagosome closure maturation and lysosome fusion → Sealing of autophagophore membrane → ESCRT-I complex component; (2) ALP same group → Localization of the ESCRT-III complex; (3) UPS Ubiquitin and UBL binding → trafficking → ESCRT-I complex → UEV (Type 2). PN-node mapping: ESCRT-I-component leaf=mapped→GO:0000813; sealing group=mapped→GO:0000045; ESCRT-III-localization leaf=no_mapping; macroautophagy class + UPS nodes=context_only/no_mapping. Projected: GO:0000045 (more_specific_than_existing_goa), GO:0000813 (already_in_goa_exact).
Consistency: Strongly consistent. VPS37A is the one VPS37 paralog with direct mammalian phagophore-closure evidence (PMID:31519728), and the review uniquely adds GO:0000045 as a NEW annotation (plus MODIFY of GO:0006612/GO:0016236→GO:0000045). PN's two projections (GO:0000813 ESCRT-I; GO:0000045 autophagosome assembly) match the review exactly. The UEV/UPS placement aligns with ESCRT-I/ubiquitin cargo sorting (review accepts GO:0043162, GO:0036258, GO:0000813).
PN story / NEW pressure: Already captured. PN asserts phagophore sealing → the review independently makes GO:0000045 a NEW term (verified real via OLS) supported by VPS37A-on-phagophore + VPS28/CHMP2A recruitment evidence. No additional new term warranted; PN adds nothing the review lacks.
Mapping strategy: No change. VPS37A is the strongest evidence anchor for the sealing-group→GO:0000045 mapping; its direct IMP/PMID:31519728 data justify the group projection for this gene. ESCRT-III-localization leaf no_mapping is correct (mixed gene set). Unlike the TOMM20/HSPA8 over-reach pattern, this projection is narrower than GOA and the review agrees.
Evidence alignment: Strong overlap. PN cites the ESCRT-I scaffold paper (=PMID:32424346) and "VPS37A directs ESCRT recruitment for phagophore closure" (=PMID:31519728), both load-bearing in the review. PN's MDPI "Key Regulators of Autophagosome Closure" review is not cited; the review uses primary literature instead.
Verdict: Fully consistent; PN projections match the review's accepted/NEW terms. No edits needed.

PN Dossier Context

review_batch: proteostasis-pr-1217
review_yaml: genes/human/VPS37A/VPS37A-ai-review.yaml
PN workbook rows: 3

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

UniProt: Q8NEZ2
In branches: ALP, UPS
Notes: Component of the ESCRT-I complex, involved in autophagosome closure. Specifically called out for directing recruitment of ESCRT machinery to autophagophore. Also, localizes to phagophore and recruits ESCRT machinery for phagophore closure
PN references (titles):
- A helical assembly of human ESCRT-I scaffolds reverse-topology membrane scission | Nature Structural & Molecular Biology
- VPS37A directs ESCRT recruitment for phagophore closure | Journal of Cell Biology | Rockefeller University Press (rupress.org)
- Cells | Free Full-Text | Key Regulators of Autophagosome Closure (mdpi.com)
PN-node mapping records (path + ancestors):
- [type] Autophagy-Lysosome Pathway|Autophagosome closure maturation and lysosome fusion|Sealing of autophagophore membrane|ESCRT-I complex component
  status=mapped scope=ok_for_propagation_to_go GO=[GO:0000813 ESCRT I complex]
  rationale: This leaf is restricted to ESCRT-I components used in autophagophore sealing. The shared GO assertion is ESCRT I complex membership.
- [group] Autophagy-Lysosome Pathway|Autophagosome closure maturation and lysosome fusion|Sealing of autophagophore membrane
  status=mapped scope=ok_for_propagation_to_go GO=[GO:0000045 autophagosome assembly]
  rationale: This group captures autophagophore closure/sealing, a late step in autophagosome assembly. Autophagosome assembly is the safer process target than autophagosome-lysosome fusion.
- [class] Autophagy-Lysosome Pathway|Autophagosome closure maturation and lysosome fusion
  status=context_only scope=too_broad_to_propagate GO=[GO:0016236 macroautophagy]
  rationale: This class is a late macroautophagy context, but the subtree mixes docking, fusion, localization, membrane-composition, and unknown late-stage roles. The class-level relation is useful for display while propagation is restricted to narrower mechanism nodes.
- [branch] Autophagy-Lysosome Pathway
  status=no_mapping scope= GO=[]
  rationale: Reviewed as the top-level PN branch. It is a project taxonomy umbrella rather than a direct GO assertion; all propagation must come from manually curated child nodes.

PN row 2: Autophagy-Lysosome Pathway | Autophagosome closure maturation and lysosome fusion | Sealing of autophagophore membrane | Localization of the ESCRT-III complex

UniProt: Q8NEZ2
In branches: ALP, UPS
Notes: Component of the ESCRT-I complex, involved in autophagosome closure. Specifically called out for directing recruitment of ESCRT machinery to autophagophore. Also, localizes to phagophore and recruits ESCRT machinery for phagophore closure
PN references (titles):
- A helical assembly of human ESCRT-I scaffolds reverse-topology membrane scission | Nature Structural & Molecular Biology
- VPS37A directs ESCRT recruitment for phagophore closure | Journal of Cell Biology | Rockefeller University Press (rupress.org)
- Cells | Free Full-Text | Key Regulators of Autophagosome Closure (mdpi.com)
PN-node mapping records (path + ancestors):
- [type] Autophagy-Lysosome Pathway|Autophagosome closure maturation and lysosome fusion|Sealing of autophagophore membrane|Localization of the ESCRT-III complex
  status=no_mapping scope= GO=[]
  rationale: This PN leaf groups factors that affect ESCRT-III localization during sealing, but the current member set mixes endosomal sorting and SNARE trafficking genes rather than one clean shared autophagy-specific GO term.
- [group] Autophagy-Lysosome Pathway|Autophagosome closure maturation and lysosome fusion|Sealing of autophagophore membrane
  status=mapped scope=ok_for_propagation_to_go GO=[GO:0000045 autophagosome assembly]
  rationale: This group captures autophagophore closure/sealing, a late step in autophagosome assembly. Autophagosome assembly is the safer process target than autophagosome-lysosome fusion.
- [class] Autophagy-Lysosome Pathway|Autophagosome closure maturation and lysosome fusion
  status=context_only scope=too_broad_to_propagate GO=[GO:0016236 macroautophagy]
  rationale: This class is a late macroautophagy context, but the subtree mixes docking, fusion, localization, membrane-composition, and unknown late-stage roles. The class-level relation is useful for display while propagation is restricted to narrower mechanism nodes.
- [branch] Autophagy-Lysosome Pathway
  status=no_mapping scope= GO=[]
  rationale: Reviewed as the top-level PN branch. It is a project taxonomy umbrella rather than a direct GO assertion; all propagation must come from manually curated child nodes.

PN row 3: Ubiquitin Proteasome System | Ubiquitin and UBL binding | trafficking | ESCRT-I complex | UEV (Type 2)

UniProt: Q8NEZ2
In branches: ALP, UPS
Signature domains: cd11685
Auxiliary domains: (none)
PN-node mapping records (path + ancestors):
- [subtype] Ubiquitin Proteasome System|Ubiquitin and UBL binding|trafficking|ESCRT-I complex|UEV (Type 2)
  status=no_mapping scope= GO=[]
  rationale: Reviewed manually as a UPS source node. No single GO term is appropriate for direct propagation from this PN label without narrower context or gene-level evidence.
- [type] Ubiquitin Proteasome System|Ubiquitin and UBL binding|trafficking|ESCRT-I complex
  status=no_mapping scope= GO=[]
  rationale: Reviewed as a UPS taxonomy container. Its descendants mix catalytic roles, complex membership, binding domains, regulators, adaptors, and substrate-context labels, so a single propagating GO assertion would overstate the shared biology.
- [group] Ubiquitin Proteasome System|Ubiquitin and UBL binding|trafficking
  status=no_mapping scope= GO=[]
  rationale: Reviewed as a UPS taxonomy container. Its descendants mix catalytic roles, complex membership, binding domains, regulators, adaptors, and substrate-context labels, so a single propagating GO assertion would overstate the shared biology.
- [class] Ubiquitin Proteasome System|Ubiquitin and UBL binding
  status=context_only scope=too_broad_to_propagate GO=[GO:0140036 ubiquitin-modified protein reader activity]
  rationale: This class records ubiquitin/UBL-reader context, but the subtree mixes ubiquitin, SUMO, UBL-domain, domain-architecture, catalytic, signaling, trafficking, and nucleic-acid process buckets. It is useful context, not a safe direct propagation.
- [branch] Ubiquitin Proteasome System
  status=no_mapping scope= GO=[]
  rationale: Reviewed as the top-level UPS branch. It is a project taxonomy umbrella rather than a direct GO assertion; UPS propagation must come from manually curated child nodes.

Projected GO annotations (3)

GO:0000045 autophagosome assembly | scope=ok_for_propagation_to_go | goa_status=more_specific_than_existing_goa | from=Autophagy-Lysosome Pathway|Autophagosome closure maturation and lysosome fusion|Sealing of autophagophore membrane
GO:0000813 ESCRT I complex | scope=ok_for_propagation_to_go | goa_status=already_in_goa_exact | from=Autophagy-Lysosome Pathway|Autophagosome closure maturation and lysosome fusion|Sealing of autophagophore membrane|ESCRT-I complex component
GO:0000045 autophagosome assembly | scope=ok_for_propagation_to_go | goa_status=more_specific_than_existing_goa | from=Autophagy-Lysosome Pathway|Autophagosome closure maturation and lysosome fusion|Sealing of autophagophore membrane

Note

This file is generated from the current PROTEOSTASIS phase-1 dossier and local gene-review artifacts. Edit the source review, PN mapping, or dossier rather than this generated note when correcting the underlying curation.

📄 View Raw YAML

id: Q8NEZ2
gene_symbol: VPS37A
product_type: PROTEIN
status: COMPLETE
taxon:
  id: NCBITaxon:9606
  label: Homo sapiens
description: >-
  VPS37A is a VPS37-family ESCRT-I subunit that complexes with TSG101, VPS28, and MVB12/UBAP-family
  subunits. It supports ubiquitin-dependent endosomal cargo sorting into multivesicular bodies and has
  a directly tested role in phagophore closure, where its PUEV-containing N terminus recruits ESCRT
  machinery for autophagosome completion.
alternative_products:
- name: '1'
  id: Q8NEZ2-1
- name: 2 (beta)
  id: Q8NEZ2-2
  sequence_note: VSP_025367
- name: '3'
  id: Q8NEZ2-3
  sequence_note: VSP_025368, VSP_025369
existing_annotations:
- term:
    id: GO:0043162
    label: ubiquitin-dependent protein catabolic process via the multivesicular body sorting pathway
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: involved_in
  review:
    summary: ubiquitin-dependent protein catabolic process via the multivesicular body sorting pathway is 
      supported as part of the core VPS37A/ESCRT-I endosomal cargo-sorting role.
    action: ACCEPT
    reason: VPS37A is required for ESCRT-I-dependent sorting of ubiquitinated endocytic cargos, including 
      EGFR, into MVB/lysosomal routes.
    additional_reference_ids: &id001
    - PMID:15240819
    - PMID:21757351
    - file:human/VPS37A/VPS37A-uniprot.txt
    - file:human/VPS37A/VPS37A-notes.md
    supported_by: &id002
    - &id014
      reference_id: file:human/VPS37A/VPS37A-uniprot.txt
      supporting_text: Required for the sorting of endocytic
    - &id015
      reference_id: file:human/VPS37A/VPS37A-uniprot.txt
      supporting_text: ubiquitinated cargos into multivesicular bodies
    - &id016
      reference_id: PMID:15240819
      supporting_text: retards epidermal growth factor (EGF) receptor degradation
    - &id017
      reference_id: PMID:15240819
      supporting_text: essential for lysosomal sorting of EGF receptors
    - &id018
      reference_id: PMID:21757351
      supporting_text: required for sorting EGFR to the MVB
- term:
    id: GO:0000813
    label: ESCRT I complex
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: part_of
  review:
    summary: ESCRT-I complex membership is the central VPS37A cellular-component annotation.
    action: ACCEPT
    reason: VPS37A is the VPS37-family ESCRT-I subunit in TSG101-VPS28-VPS37-MVB12/UBAP variant complexes.
    additional_reference_ids: &id003
    - PMID:15240819
    - PMID:18005716
    - PMID:21757351
    - file:human/VPS37A/VPS37A-uniprot.txt
    - file:human/VPS37A/VPS37A-notes.md
    supported_by: &id004
    - &id009
      reference_id: file:human/VPS37A/VPS37A-uniprot.txt
      supporting_text: Component of the ESCRT-I complex
    - &id010
      reference_id: file:human/VPS37A/VPS37A-uniprot.txt
      supporting_text: which consists of TSG101, VPS28, a VPS37
    - &id011
      reference_id: file:human/VPS37A/VPS37A-uniprot.txt
      supporting_text: Interacts with TSG101, VPS28 and HGS
    - &id012
      reference_id: PMID:15240819
      supporting_text: a subunit of mammalian ESCRT-I
    - &id013
      reference_id: PMID:21757351
      supporting_text: Mammalian ESCRT-I comprises TSG101, VPS28, VPS37A-D, and MVB12A/B
- term:
    id: GO:0006612
    label: protein targeting to membrane
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: involved_in
  review:
    summary: Protein targeting to membrane is too broad for the VPS37A phagophore recruitment role.
    action: MODIFY
    reason: The direct VPS37A evidence concerns ESCRT recruitment to phagophores and autophagosome completion,
      which is better captured as GO:0000045 autophagosome assembly.
    proposed_replacement_terms:
    - id: GO:0000045
      label: autophagosome assembly
    additional_reference_ids: &id005
    - PMID:31519728
    - PMID:32424346
    - file:human/VPS37A/VPS37A-notes.md
    supported_by: &id006
    - &id024
      reference_id: PMID:31519728
      supporting_text: the ESCRT-I subunit VPS37A as a critical component for phagophore closure
    - &id025
      reference_id: PMID:31519728
      supporting_text: VPS37A localizes on the phagophore
    - &id026
      reference_id: PMID:31519728
      supporting_text: required for autophagosome completion but dispensable for ESCRT-I complex formation
    - &id027
      reference_id: PMID:31519728
      supporting_text: loss of VPS37A abrogates the phagophore recruitment
    - &id028
      reference_id: PMID:32424346
      supporting_text: ESCRT-I helical interface is required for autophagosome closure
- term:
    id: GO:0006623
    label: protein targeting to vacuole
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: involved_in
  review:
    summary: Protein targeting to vacuole is too broad for the VPS37A endosomal sorting evidence.
    action: MODIFY
    reason: The supported process is ubiquitin-dependent MVB sorting and lysosomal routing of endocytic cargo,
      not generic protein targeting to vacuole.
    proposed_replacement_terms:
    - id: GO:0043162
      label: ubiquitin-dependent protein catabolic process via the multivesicular body sorting pathway
    - id: GO:0043328
      label: protein transport to vacuole involved in ubiquitin-dependent protein catabolic process via the 
        multivesicular body sorting pathway
    additional_reference_ids: *id001
    supported_by: *id002
- term:
    id: GO:0000813
    label: ESCRT I complex
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  qualifier: part_of
  review:
    summary: ESCRT-I complex membership is the central VPS37A cellular-component annotation.
    action: ACCEPT
    reason: VPS37A is the VPS37-family ESCRT-I subunit in TSG101-VPS28-VPS37-MVB12/UBAP variant complexes.
    additional_reference_ids: *id003
    supported_by: *id004
- term:
    id: GO:0005634
    label: nucleus
  evidence_type: IEA
  original_reference_id: GO_REF:0000044
  qualifier: located_in
  review:
    summary: nucleus is supported as a secondary context but is not the core VPS37A proteostasis function.
    action: KEEP_AS_NON_CORE
    reason: Viral budding and nuclear/nucleoplasm localizations are secondary observations or contexts; the 
      core function is ESCRT-I endosomal sorting and phagophore closure.
    additional_reference_ids: &id007
    - PMID:18005716
    - PMID:20588296
    - file:human/VPS37A/VPS37A-uniprot.txt
    - file:human/VPS37A/VPS37A-notes.md
    supported_by: &id008
    - reference_id: PMID:18005716
      supporting_text: plays essential roles in HIV budding and endosomal protein sorting
    - reference_id: PMID:20588296
      supporting_text: viral budding, cytokinesis and, probably, autophagy
    - reference_id: file:human/VPS37A/VPS37A-uniprot.txt
      supporting_text: Nucleus
- term:
    id: GO:0016236
    label: macroautophagy
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  qualifier: involved_in
  review:
    summary: Macroautophagy is too broad for the directly tested VPS37A role.
    action: MODIFY
    reason: VPS37A is directly required for phagophore closure/autophagosome completion, so GO:0000045 
      autophagosome assembly is the more precise term.
    proposed_replacement_terms:
    - id: GO:0000045
      label: autophagosome assembly
    additional_reference_ids: *id005
    supported_by: *id006
- term:
    id: GO:0031902
    label: late endosome membrane
  evidence_type: IEA
  original_reference_id: GO_REF:0000044
  qualifier: located_in
  review:
    summary: late endosome membrane localization is supported and relevant to VPS37A/ESCRT-I function.
    action: ACCEPT
    reason: VPS37A is a peripheral late-endosome/endosome-membrane ESCRT-I component and colocalizes with 
      hVps28 on LAMP1-positive endosomes.
    additional_reference_ids: &id020
    - PMID:15240819
    - file:human/VPS37A/VPS37A-uniprot.txt
    - file:human/VPS37A/VPS37A-notes.md
    supported_by: &id021
    - &id022
      reference_id: file:human/VPS37A/VPS37A-uniprot.txt
      supporting_text: Late endosome membrane
    - &id023
      reference_id: PMID:15240819
      supporting_text: colocalizes with hVps28 on LAMP1-positive endosomes
- term:
    id: GO:0036258
    label: multivesicular body assembly
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  qualifier: involved_in
  review:
    summary: multivesicular body assembly is supported as part of the core VPS37A/ESCRT-I endosomal 
      cargo-sorting role.
    action: ACCEPT
    reason: VPS37A is required for ESCRT-I-dependent sorting of ubiquitinated endocytic cargos, including 
      EGFR, into MVB/lysosomal routes.
    additional_reference_ids: *id001
    supported_by: *id002
- term:
    id: GO:0039702
    label: viral budding via host ESCRT complex
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  qualifier: involved_in
  review:
    summary: viral budding via host ESCRT complex is supported as a secondary context but is not the core 
      VPS37A proteostasis function.
    action: KEEP_AS_NON_CORE
    reason: Viral budding and nuclear/nucleoplasm localizations are secondary observations or contexts; the 
      core function is ESCRT-I endosomal sorting and phagophore closure.
    additional_reference_ids: *id007
    supported_by: *id008
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:25416956
  qualifier: enables
  review:
    summary: Protein binding is too generic to represent VPS37A function.
    action: MARK_AS_OVER_ANNOTATED
    reason: The informative biology is ESCRT-I complex membership, endosomal MVB sorting, and 
      phagophore-closure recruitment, not generic protein binding from interaction assays.
    proposed_replacement_terms: &id019
    - id: GO:0000813
      label: ESCRT I complex
    - id: GO:0043162
      label: ubiquitin-dependent protein catabolic process via the multivesicular body sorting pathway
    additional_reference_ids:
    - PMID:15240819
    - PMID:18005716
    - PMID:21757351
    - file:human/VPS37A/VPS37A-uniprot.txt
    - file:human/VPS37A/VPS37A-notes.md
    - PMID:15240819
    - PMID:21757351
    - file:human/VPS37A/VPS37A-uniprot.txt
    - file:human/VPS37A/VPS37A-notes.md
    supported_by:
    - *id009
    - *id010
    - *id011
    - *id012
    - *id013
    - *id014
    - *id015
    - *id016
    - *id017
    - *id018
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:32296183
  qualifier: enables
  review:
    summary: Protein binding is too generic to represent VPS37A function.
    action: MARK_AS_OVER_ANNOTATED
    reason: The informative biology is ESCRT-I complex membership, endosomal MVB sorting, and 
      phagophore-closure recruitment, not generic protein binding from interaction assays.
    proposed_replacement_terms: *id019
    additional_reference_ids:
    - PMID:15240819
    - PMID:18005716
    - PMID:21757351
    - file:human/VPS37A/VPS37A-uniprot.txt
    - file:human/VPS37A/VPS37A-notes.md
    - PMID:15240819
    - PMID:21757351
    - file:human/VPS37A/VPS37A-uniprot.txt
    - file:human/VPS37A/VPS37A-notes.md
    supported_by:
    - *id009
    - *id010
    - *id011
    - *id012
    - *id013
    - *id014
    - *id015
    - *id016
    - *id017
    - *id018
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:32814053
  qualifier: enables
  review:
    summary: Protein binding is too generic to represent VPS37A function.
    action: MARK_AS_OVER_ANNOTATED
    reason: The informative biology is ESCRT-I complex membership, endosomal MVB sorting, and 
      phagophore-closure recruitment, not generic protein binding from interaction assays.
    proposed_replacement_terms: *id019
    additional_reference_ids:
    - PMID:15240819
    - PMID:18005716
    - PMID:21757351
    - file:human/VPS37A/VPS37A-uniprot.txt
    - file:human/VPS37A/VPS37A-notes.md
    - PMID:15240819
    - PMID:21757351
    - file:human/VPS37A/VPS37A-uniprot.txt
    - file:human/VPS37A/VPS37A-notes.md
    supported_by:
    - *id009
    - *id010
    - *id011
    - *id012
    - *id013
    - *id014
    - *id015
    - *id016
    - *id017
    - *id018
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:33961781
  qualifier: enables
  review:
    summary: Protein binding is too generic to represent VPS37A function.
    action: MARK_AS_OVER_ANNOTATED
    reason: The informative biology is ESCRT-I complex membership, endosomal MVB sorting, and 
      phagophore-closure recruitment, not generic protein binding from interaction assays.
    proposed_replacement_terms: *id019
    additional_reference_ids:
    - PMID:15240819
    - PMID:18005716
    - PMID:21757351
    - file:human/VPS37A/VPS37A-uniprot.txt
    - file:human/VPS37A/VPS37A-notes.md
    - PMID:15240819
    - PMID:21757351
    - file:human/VPS37A/VPS37A-uniprot.txt
    - file:human/VPS37A/VPS37A-notes.md
    supported_by:
    - *id009
    - *id010
    - *id011
    - *id012
    - *id013
    - *id014
    - *id015
    - *id016
    - *id017
    - *id018
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:35271311
  qualifier: enables
  review:
    summary: Protein binding is too generic to represent VPS37A function.
    action: MARK_AS_OVER_ANNOTATED
    reason: The informative biology is ESCRT-I complex membership, endosomal MVB sorting, and 
      phagophore-closure recruitment, not generic protein binding from interaction assays.
    proposed_replacement_terms: *id019
    additional_reference_ids:
    - PMID:15240819
    - PMID:18005716
    - PMID:21757351
    - file:human/VPS37A/VPS37A-uniprot.txt
    - file:human/VPS37A/VPS37A-notes.md
    - PMID:15240819
    - PMID:21757351
    - file:human/VPS37A/VPS37A-uniprot.txt
    - file:human/VPS37A/VPS37A-notes.md
    supported_by:
    - *id009
    - *id010
    - *id011
    - *id012
    - *id013
    - *id014
    - *id015
    - *id016
    - *id017
    - *id018
- term:
    id: GO:0005654
    label: nucleoplasm
  evidence_type: IDA
  original_reference_id: GO_REF:0000052
  qualifier: located_in
  review:
    summary: nucleoplasm is supported as a secondary context but is not the core VPS37A proteostasis function.
    action: KEEP_AS_NON_CORE
    reason: Viral budding and nuclear/nucleoplasm localizations are secondary observations or contexts; the 
      core function is ESCRT-I endosomal sorting and phagophore closure.
    additional_reference_ids: *id007
    supported_by: *id008
- term:
    id: GO:0010008
    label: endosome membrane
  evidence_type: NAS
  original_reference_id: PMID:32424346
  qualifier: located_in
  review:
    summary: endosome membrane localization is supported and relevant to VPS37A/ESCRT-I function.
    action: ACCEPT
    reason: VPS37A is a peripheral late-endosome/endosome-membrane ESCRT-I component and colocalizes with 
      hVps28 on LAMP1-positive endosomes.
    additional_reference_ids: *id020
    supported_by: *id021
- term:
    id: GO:0036258
    label: multivesicular body assembly
  evidence_type: NAS
  original_reference_id: PMID:32424346
  qualifier: involved_in
  review:
    summary: multivesicular body assembly is supported as part of the core VPS37A/ESCRT-I endosomal 
      cargo-sorting role.
    action: ACCEPT
    reason: VPS37A is required for ESCRT-I-dependent sorting of ubiquitinated endocytic cargos, including 
      EGFR, into MVB/lysosomal routes.
    additional_reference_ids: *id001
    supported_by: *id002
- term:
    id: GO:0043328
    label: protein transport to vacuole involved in ubiquitin-dependent protein catabolic process via the 
      multivesicular body sorting pathway
  evidence_type: NAS
  original_reference_id: PMID:32424346
  qualifier: involved_in
  review:
    summary: protein transport to vacuole involved in ubiquitin-dependent protein catabolic process via the 
      multivesicular body sorting pathway is supported as part of the core VPS37A/ESCRT-I endosomal 
      cargo-sorting role.
    action: ACCEPT
    reason: VPS37A is required for ESCRT-I-dependent sorting of ubiquitinated endocytic cargos, including 
      EGFR, into MVB/lysosomal routes.
    additional_reference_ids: *id001
    supported_by: *id002
- term:
    id: GO:0090148
    label: membrane fission
  evidence_type: NAS
  original_reference_id: PMID:32424346
  qualifier: involved_in
  review:
    summary: Membrane fission is supported for ESCRT-I reverse-topology membrane remodeling.
    action: ACCEPT
    reason: VPS37A is a core ESCRT-I component; ESCRT-I scaffolds upstream ESCRT recruitment for 
      reverse-topology membrane remodeling, including phagophore closure.
    additional_reference_ids:
    - PMID:20588296
    - PMID:31519728
    - PMID:32424346
    - file:human/VPS37A/VPS37A-notes.md
    supported_by:
    - reference_id: PMID:20588296
      supporting_text: ESCRT-I and ESCRT-II direct membrane budding away from the cytosol
    - reference_id: PMID:31519728
      supporting_text: VPS37A coordinates the recruitment of a unique set of ESCRT machinery components for 
        phagophore closure
    - reference_id: PMID:32424346
      supporting_text: A helical assembly of human ESCRT-I scaffolds reverse-topology membrane scission
- term:
    id: GO:0000813
    label: ESCRT I complex
  evidence_type: IPI
  original_reference_id: PMID:18005716
  qualifier: part_of
  review:
    summary: ESCRT-I complex membership is the central VPS37A cellular-component annotation.
    action: ACCEPT
    reason: VPS37A is the VPS37-family ESCRT-I subunit in TSG101-VPS28-VPS37-MVB12/UBAP variant complexes.
    additional_reference_ids: *id003
    supported_by: *id004
- term:
    id: GO:0000813
    label: ESCRT I complex
  evidence_type: IPI
  original_reference_id: PMID:21757351
  qualifier: part_of
  review:
    summary: ESCRT-I complex membership is the central VPS37A cellular-component annotation.
    action: ACCEPT
    reason: VPS37A is the VPS37-family ESCRT-I subunit in TSG101-VPS28-VPS37-MVB12/UBAP variant complexes.
    additional_reference_ids: *id003
    supported_by: *id004
- term:
    id: GO:0016236
    label: macroautophagy
  evidence_type: TAS
  original_reference_id: PMID:20588296
  qualifier: involved_in
  review:
    summary: Macroautophagy is too broad for the directly tested VPS37A role.
    action: MODIFY
    reason: VPS37A is directly required for phagophore closure/autophagosome completion, so GO:0000045 
      autophagosome assembly is the more precise term.
    proposed_replacement_terms:
    - id: GO:0000045
      label: autophagosome assembly
    additional_reference_ids: *id005
    supported_by: *id006
- term:
    id: GO:0000813
    label: ESCRT I complex
  evidence_type: TAS
  original_reference_id: PMID:20588296
  qualifier: part_of
  review:
    summary: ESCRT-I complex membership is the central VPS37A cellular-component annotation.
    action: ACCEPT
    reason: VPS37A is the VPS37-family ESCRT-I subunit in TSG101-VPS28-VPS37-MVB12/UBAP variant complexes.
    additional_reference_ids: *id003
    supported_by: *id004
- term:
    id: GO:0036258
    label: multivesicular body assembly
  evidence_type: TAS
  original_reference_id: PMID:20588296
  qualifier: involved_in
  review:
    summary: multivesicular body assembly is supported as part of the core VPS37A/ESCRT-I endosomal 
      cargo-sorting role.
    action: ACCEPT
    reason: VPS37A is required for ESCRT-I-dependent sorting of ubiquitinated endocytic cargos, including 
      EGFR, into MVB/lysosomal routes.
    additional_reference_ids: *id001
    supported_by: *id002
- term:
    id: GO:0039702
    label: viral budding via host ESCRT complex
  evidence_type: TAS
  original_reference_id: PMID:20588296
  qualifier: involved_in
  review:
    summary: viral budding via host ESCRT complex is supported as a secondary context but is not the core 
      VPS37A proteostasis function.
    action: KEEP_AS_NON_CORE
    reason: Viral budding and nuclear/nucleoplasm localizations are secondary observations or contexts; the 
      core function is ESCRT-I endosomal sorting and phagophore closure.
    additional_reference_ids: *id007
    supported_by: *id008
- term:
    id: GO:0000813
    label: ESCRT I complex
  evidence_type: IDA
  original_reference_id: PMID:18005716
  qualifier: part_of
  review:
    summary: ESCRT-I complex membership is the central VPS37A cellular-component annotation.
    action: ACCEPT
    reason: VPS37A is the VPS37-family ESCRT-I subunit in TSG101-VPS28-VPS37-MVB12/UBAP variant complexes.
    additional_reference_ids: *id003
    supported_by: *id004
- term:
    id: GO:0000813
    label: ESCRT I complex
  evidence_type: IDA
  original_reference_id: PMID:20654576
  qualifier: part_of
  review:
    summary: ESCRT-I complex membership is the central VPS37A cellular-component annotation.
    action: ACCEPT
    reason: VPS37A is the VPS37-family ESCRT-I subunit in TSG101-VPS28-VPS37-MVB12/UBAP variant complexes.
    additional_reference_ids: *id003
    supported_by: *id004
- term:
    id: GO:0043162
    label: ubiquitin-dependent protein catabolic process via the multivesicular body sorting pathway
  evidence_type: IC
  original_reference_id: PMID:20654576
  qualifier: involved_in
  review:
    summary: ubiquitin-dependent protein catabolic process via the multivesicular body sorting pathway is 
      supported as part of the core VPS37A/ESCRT-I endosomal cargo-sorting role.
    action: ACCEPT
    reason: VPS37A is required for ESCRT-I-dependent sorting of ubiquitinated endocytic cargos, including 
      EGFR, into MVB/lysosomal routes.
    additional_reference_ids: *id001
    supported_by: *id002
- term:
    id: GO:0000813
    label: ESCRT I complex
  evidence_type: IDA
  original_reference_id: PMID:21757351
  qualifier: part_of
  review:
    summary: ESCRT-I complex membership is the central VPS37A cellular-component annotation.
    action: ACCEPT
    reason: VPS37A is the VPS37-family ESCRT-I subunit in TSG101-VPS28-VPS37-MVB12/UBAP variant complexes.
    additional_reference_ids: *id003
    supported_by: *id004
- term:
    id: GO:0043162
    label: ubiquitin-dependent protein catabolic process via the multivesicular body sorting pathway
  evidence_type: IMP
  original_reference_id: PMID:21757351
  qualifier: involved_in
  review:
    summary: ubiquitin-dependent protein catabolic process via the multivesicular body sorting pathway is 
      supported as part of the core VPS37A/ESCRT-I endosomal cargo-sorting role.
    action: ACCEPT
    reason: VPS37A is required for ESCRT-I-dependent sorting of ubiquitinated endocytic cargos, including 
      EGFR, into MVB/lysosomal routes.
    additional_reference_ids: *id001
    supported_by: *id002
- term:
    id: GO:0010008
    label: endosome membrane
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-184269
  qualifier: located_in
  review:
    summary: endosome membrane localization is supported and relevant to VPS37A/ESCRT-I function.
    action: ACCEPT
    reason: VPS37A is a peripheral late-endosome/endosome-membrane ESCRT-I component and colocalizes with 
      hVps28 on LAMP1-positive endosomes.
    additional_reference_ids: *id020
    supported_by: *id021
- term:
    id: GO:0010008
    label: endosome membrane
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-3149434
  qualifier: located_in
  review:
    summary: endosome membrane localization is supported and relevant to VPS37A/ESCRT-I function.
    action: ACCEPT
    reason: VPS37A is a peripheral late-endosome/endosome-membrane ESCRT-I component and colocalizes with 
      hVps28 on LAMP1-positive endosomes.
    additional_reference_ids: *id020
    supported_by: *id021
- term:
    id: GO:0010008
    label: endosome membrane
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-3159232
  qualifier: located_in
  review:
    summary: endosome membrane localization is supported and relevant to VPS37A/ESCRT-I function.
    action: ACCEPT
    reason: VPS37A is a peripheral late-endosome/endosome-membrane ESCRT-I component and colocalizes with 
      hVps28 on LAMP1-positive endosomes.
    additional_reference_ids: *id020
    supported_by: *id021
- term:
    id: GO:0010008
    label: endosome membrane
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-917696
  qualifier: located_in
  review:
    summary: endosome membrane localization is supported and relevant to VPS37A/ESCRT-I function.
    action: ACCEPT
    reason: VPS37A is a peripheral late-endosome/endosome-membrane ESCRT-I component and colocalizes with 
      hVps28 on LAMP1-positive endosomes.
    additional_reference_ids: *id020
    supported_by: *id021
- term:
    id: GO:0010008
    label: endosome membrane
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-917730
  qualifier: located_in
  review:
    summary: endosome membrane localization is supported and relevant to VPS37A/ESCRT-I function.
    action: ACCEPT
    reason: VPS37A is a peripheral late-endosome/endosome-membrane ESCRT-I component and colocalizes with 
      hVps28 on LAMP1-positive endosomes.
    additional_reference_ids: *id020
    supported_by: *id021
- term:
    id: GO:0000045
    label: autophagosome assembly
  evidence_type: IMP
  original_reference_id: PMID:31519728
  qualifier: involved_in
  review:
    summary: VPS37A should be annotated to autophagosome assembly for its direct phagophore-closure role.
    action: NEW
    reason: VPS37A is directly identified as an ESCRT-I component required for phagophore 
      closure/autophagosome completion, and loss of VPS37A blocks recruitment of VPS28 and CHMP2A.
    additional_reference_ids: *id005
    supported_by: *id006
references:
- id: GO_REF:0000033
  title: Annotation inferences using phylogenetic trees
  findings: []
- id: GO_REF:0000044
  title: Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular Location vocabulary mapping, 
    accompanied by conservative changes to GO terms applied by UniProt
  findings: []
- id: GO_REF:0000052
  title: Gene Ontology annotation based on curation of immunofluorescence data
  findings: []
- id: GO_REF:0000117
  title: Electronic Gene Ontology annotations created by ARBA machine learning models
  findings: []
- id: PMID:18005716
  title: Identification of human MVB12 proteins as ESCRT-I subunits that function in HIV budding.
  findings: []
- id: PMID:20588296
  title: "Membrane budding and scission by the ESCRT machinery: it's all in the neck."
  findings: []
- id: PMID:20654576
  title: Distinct functions of human MVB12A and MVB12B in the ESCRT-I dependent on their posttranslational 
    modifications.
  findings: []
- id: PMID:21757351
  title: UBAP1 is a component of an endosome-specific ESCRT-I complex that is essential for MVB sorting.
  findings: []
- id: PMID:25416956
  title: A proteome-scale map of the human interactome network.
  findings: []
- id: PMID:32296183
  title: A reference map of the human binary protein interactome.
  findings: []
- id: PMID:32424346
  title: A helical assembly of human ESCRT-I scaffolds reverse-topology membrane scission.
  findings: []
- id: PMID:32814053
  title: Interactome Mapping Provides a Network of Neurodegenerative Disease Proteins and Uncovers Widespread 
    Protein Aggregation in Affected Brains.
  findings: []
- id: PMID:33961781
  title: Dual proteome-scale networks reveal cell-specific remodeling of the human interactome.
  findings: []
- id: PMID:35271311
  title: 'OpenCell: Endogenous tagging for the cartography of human cellular organization.'
  findings: []
- id: Reactome:R-HSA-184269
  title: Monoubiquitinated N-myristoyl GAG polyprotein is targeted to the late endosomal vesicle membrane by 
    the ESCRT-I complex
  findings: []
- id: Reactome:R-HSA-3149434
  title: Transport of GAG to the Plasma Membrane
  findings: []
- id: Reactome:R-HSA-3159232
  title: Recruitment Of HIV Virion Budding Machinery
  findings: []
- id: Reactome:R-HSA-917696
  title: Cargo Sequestration
  findings: []
- id: Reactome:R-HSA-917730
  title: Cargo Recognition And Sorting
  findings: []
- id: PMID:15240819
  title: The growth-regulatory protein HCRP1/hVps37A is a subunit of mammalian ESCRT-I and mediates receptor 
    down-regulation.
  findings: []
- id: PMID:31519728
  title: VPS37A directs ESCRT recruitment for phagophore closure.
  findings: []
- id: file:human/VPS37A/VPS37A-uniprot.txt
  title: UniProtKB record for human VPS37A
  findings: []
- id: file:human/VPS37A/VPS37A-notes.md
  title: VPS37A review notes
  findings: []
core_functions:
- description: VPS37A is an ESCRT-I subunit that organizes endosomal MVB cargo sorting and, through its 
    PUEV-containing phagophore-targeting function, coordinates recruitment of VPS28 and ESCRT-III machinery 
    for autophagosome completion.
  directly_involved_in:
  - id: GO:0043162
    label: ubiquitin-dependent protein catabolic process via the multivesicular body sorting pathway
  - id: GO:0036258
    label: multivesicular body assembly
  - id: GO:0090148
    label: membrane fission
  - id: GO:0000045
    label: autophagosome assembly
  locations:
  - id: GO:0010008
    label: endosome membrane
  - id: GO:0031902
    label: late endosome membrane
  in_complex:
    id: GO:0000813
    label: ESCRT I complex
  supported_by:
  - *id009
  - *id010
  - *id011
  - *id012
  - *id013
  - *id014
  - *id015
  - *id016
  - *id017
  - *id018
  - *id022
  - *id023
  - *id024
  - *id025
  - *id026
  - *id027
  - *id028
proposed_new_terms: []
suggested_questions:
- question: Should VPS37A macroautophagy/protein-targeting annotations be replaced by GO:0000045 autophagosome
    assembly to capture phagophore closure?
  experts:
  - GO autophagy editors
  - GO ESCRT curators
- question: Should generic VPS37A protein-binding rows be retired in favor of ESCRT-I complex membership and 
    specific endosomal/autophagy process terms?
  experts:
  - GO molecular function editors
  - UniProt curators
suggested_experiments:
- experiment_type: VPS37A isoform and PUEV-domain rescue
  hypothesis: PUEV-containing VPS37A isoforms are specifically required for phagophore closure, while the 
    ESCRT-I Mod(r) assembly domain remains sufficient for EGFR MVB sorting.
  description: Use endogenous VPS37A knockout/rescue with PUEV-containing and PUEV-lacking isoforms, then 
    assay HT-LC3 closure, VPS28/CHMP2A recruitment, and EGFR degradation in parallel.

VPS37A

Gene Description

Existing Annotations Review

Core Functions

VPS37A is an ESCRT-I subunit that organizes endosomal MVB cargo sorting and, through its PUEV-containing phagophore-targeting function, coordinates recruitment of VPS28 and ESCRT-III machinery for autophagosome completion.

References

Suggested Questions for Experts

Suggested Experiments

📚 Additional Documentation

Notes

VPS37A review notes

Scope

Evidence synthesis

Falcon

Description cleanup note

Pn Notes

VPS37A PN Consistency Notes

Source Files Checked

Deep Research Files

AIGR Review Snapshot

PN Consistency Summary

Full Consistency Review

PN Dossier Context

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

PN row 2: Autophagy-Lysosome Pathway | Autophagosome closure maturation and lysosome fusion | Sealing of autophagophore membrane | Localization of the ESCRT-III complex

PN row 3: Ubiquitin Proteasome System | Ubiquitin and UBL binding | trafficking | ESCRT-I complex | UEV (Type 2)

Projected GO annotations (3)

Note

📄 View Raw YAML