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.