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.
| 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 |
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Download this section (compressed HTML)Q: Should VPS37A macroautophagy/protein-targeting annotations be replaced by GO:0000045 autophagosome assembly to capture phagophore closure?
Suggested experts: GO autophagy editors, GO ESCRT curators
Q: Should generic VPS37A protein-binding rows be retired in favor of ESCRT-I complex membership and specific endosomal/autophagy process terms?
Suggested experts: GO molecular function editors, UniProt curators
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
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