id: Q96EY5 gene_symbol: MVB12A product_type: PROTEIN status: COMPLETE taxon: id: NCBITaxon:9606 label: Homo sapiens description: >- MVB12A is a metazoan ESCRT-I fourth subunit that complexes with TSG101, VPS28, and VPS37-family subunits. Its best-supported core cellular role is ESCRT-I-dependent sorting of ubiquitinated endosomal cargo into multivesicular bodies, supported by acidic phospholipid/ubiquitin binding, EGFR down-regulation context, and MVB12A-containing ESCRT-I structural evidence. Viral budding and virus maturation reflect pathogen exploitation of ESCRT machinery rather than the main endogenous MVB12A function. alternative_products: - name: '1' id: Q96EY5-1 - name: 2 (Delta 5) id: Q96EY5-2 sequence_note: VSP_020629 - name: 3 (Delta 8) id: Q96EY5-3 sequence_note: VSP_020630 existing_annotations: - 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 MVB12A cellular-component annotation. action: ACCEPT reason: MVB12A is a metazoan fourth subunit of ESCRT-I and is directly supported by ESCRT-I composition and structural studies. additional_reference_ids: &id005 - PMID:18005716 - PMID:20654576 - PMID:22232651 - PMID:32424346 - file:human/MVB12A/MVB12A-uniprot.txt - file:human/MVB12A/MVB12A-notes.md supported_by: &id006 - &id015 reference_id: file:human/MVB12A/MVB12A-uniprot.txt supporting_text: Component of the ESCRT-I complex - &id016 reference_id: file:human/MVB12A/MVB12A-uniprot.txt supporting_text: which consists of TSG101, VPS28, a VPS37 - &id017 reference_id: file:human/MVB12A/MVB12A-uniprot.txt supporting_text: Interacts with TSG101 - &id018 reference_id: file:human/MVB12A/MVB12A-uniprot.txt supporting_text: Interacts with VPS28 - &id019 reference_id: PMID:18005716 supporting_text: constitute the fourth class of metazoan ESCRT-I subunits - &id020 reference_id: PMID:18005716 supporting_text: one copy of each of the four subunit types - &id021 reference_id: PMID:18005716 supporting_text: associate with the core region of the binary TSG101-VPS37 complex - &id022 reference_id: PMID:32424346 supporting_text: comprising TSG101-VPS28-VPS37B-MVB12A - term: id: GO:0005829 label: cytosol evidence_type: IBA original_reference_id: GO_REF:0000033 qualifier: is_active_in review: summary: cytosol is supported as a localization/context row but is not the core MVB12A function. action: KEEP_AS_NON_CORE reason: The core proteostasis role is ESCRT-I endosomal cargo sorting; this localization is secondary or broad. additional_reference_ids: &id007 - PMID:18005716 - PMID:19056867 - PMID:23533145 - file:human/MVB12A/MVB12A-uniprot.txt - file:human/MVB12A/MVB12A-notes.md supported_by: &id008 - reference_id: file:human/MVB12A/MVB12A-uniprot.txt supporting_text: Cytoplasm - reference_id: file:human/MVB12A/MVB12A-uniprot.txt supporting_text: Nucleus - reference_id: file:human/MVB12A/MVB12A-uniprot.txt supporting_text: centrosome - reference_id: PMID:19056867 supporting_text: Large-scale proteomics and phosphoproteomics of urinary exosomes - reference_id: PMID:23533145 supporting_text: In-depth proteomic analyses of exosomes - term: id: GO:0019075 label: virus maturation evidence_type: IBA original_reference_id: GO_REF:0000033 qualifier: involved_in review: summary: virus maturation is directly supported but is a non-core host-pathogen context for this review. MVB12A-specific viral involvement now spans both HIV-1 (Morita 2007) and beta-coronaviruses, where MVB12A knockdown impairs late virion egress without blocking assembly (falcon deep research, citing Zhang 2025). action: KEEP_AS_NON_CORE reason: MVB12A/MVB12 subunits regulate HIV/viral budding and maturation, and MVB12A knockdown specifically reduces beta-coronavirus virion egress and virus-like-particle production, but these reflect viral exploitation of host ESCRT-I rather than the core endosomal ESCRT-I cargo-sorting function. additional_reference_ids: &id003 - PMID:18005716 - PMID:20588296 - PMID:32424346 - file:human/MVB12A/MVB12A-notes.md - file:human/MVB12A/MVB12A-deep-research-falcon.md supported_by: &id004 - reference_id: PMID:18005716 supporting_text: MVB12 depletion and overexpression inhibit HIV-1 infectivity - reference_id: PMID:18005716 supporting_text: aberrant virion morphologies and altered viral Gag protein processing - reference_id: PMID:32424346 supporting_text: HIV-1 release in human cells - reference_id: PMID:20588296 supporting_text: viral budding, cytokinesis and, probably, autophagy - reference_id: file:human/MVB12A/MVB12A-deep-research-falcon.md supporting_text: Knockdown of MVB12A did not affect the early stages of virion assembly, but significantly inhibited virion egress from cells - reference_id: file:human/MVB12A/MVB12A-deep-research-falcon.md supporting_text: late-acting ESCRT component in coronavirus replication - term: id: GO:0032510 label: endosome to lysosome transport via multivesicular body sorting pathway evidence_type: IBA original_reference_id: GO_REF:0000033 qualifier: involved_in review: summary: endosome to lysosome transport via multivesicular body sorting pathway is supported as part of MVB12A/ESCRT-I endosomal cargo sorting. action: ACCEPT reason: MVB12A/ESCRT-I supports ubiquitin-dependent endosomal cargo sorting, receptor down-regulation, and multivesicular body pathway transport. additional_reference_ids: &id001 - PMID:16895919 - PMID:18005716 - PMID:20654576 - file:human/MVB12A/MVB12A-uniprot.txt - file:human/MVB12A/MVB12A-notes.md supported_by: &id002 - &id029 reference_id: file:human/MVB12A/MVB12A-uniprot.txt supporting_text: Required for the sorting of endocytic - &id030 reference_id: file:human/MVB12A/MVB12A-uniprot.txt supporting_text: ubiquitinated cargos into multivesicular bodies - &id031 reference_id: PMID:18005716 supporting_text: plays essential roles in HIV budding and endosomal protein sorting - &id032 reference_id: PMID:16895919 supporting_text: accelerated the EGF receptor's down-regulation - &id033 reference_id: PMID:20654576 supporting_text: amounts of EGF receptor bound to ESCRT-I - term: id: GO:0032801 label: receptor catabolic process evidence_type: IBA original_reference_id: GO_REF:0000033 qualifier: involved_in review: summary: receptor catabolic process is supported as part of MVB12A/ESCRT-I endosomal cargo sorting. action: ACCEPT reason: MVB12A/ESCRT-I supports ubiquitin-dependent endosomal cargo sorting, receptor down-regulation, and multivesicular body pathway transport. additional_reference_ids: *id001 supported_by: *id002 - term: id: GO:0042058 label: regulation of epidermal growth factor receptor signaling pathway evidence_type: IBA original_reference_id: GO_REF:0000033 qualifier: involved_in review: summary: EGFR signaling regulation is supported as a substrate-specific MVB12A context. action: KEEP_AS_NON_CORE reason: MVB12A affects EGFR down-regulation through CD2AP/CIN85 and ESCRT-I, but EGFR signaling is a cargo/context-specific consequence rather than the core function. additional_reference_ids: &id013 - PMID:16895919 - PMID:20654576 - file:human/MVB12A/MVB12A-uniprot.txt - file:human/MVB12A/MVB12A-notes.md supported_by: &id014 - &id034 reference_id: PMID:16895919 supporting_text: phosphorylated at tyrosine 204 upon EGF stimulation - &id035 reference_id: PMID:16895919 supporting_text: accelerated the EGF receptor's down-regulation - &id036 reference_id: PMID:20654576 supporting_text: Tyr204 phosphorylation of MVB12A - &id037 reference_id: PMID:20654576 supporting_text: affects binding to CD2AP - &id038 reference_id: PMID:20654576 supporting_text: amounts of EGF receptor bound to ESCRT-I - term: id: GO:0046755 label: viral budding evidence_type: IBA original_reference_id: GO_REF:0000033 qualifier: involved_in review: summary: viral budding is directly supported but is a non-core host-pathogen context for this review. action: KEEP_AS_NON_CORE reason: MVB12A/MVB12 subunits regulate HIV/viral budding and maturation, but the core cellular proteostasis role is endosomal ESCRT-I cargo sorting. additional_reference_ids: *id003 supported_by: *id004 - term: id: GO:0000813 label: ESCRT I complex evidence_type: IEA original_reference_id: GO_REF:0000002 qualifier: part_of review: summary: ESCRT-I complex membership is the central MVB12A cellular-component annotation. action: ACCEPT reason: MVB12A is a metazoan fourth subunit of ESCRT-I and is directly supported by ESCRT-I composition and structural studies. additional_reference_ids: *id005 supported_by: *id006 - 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 localization/context row but is not the core MVB12A function. action: KEEP_AS_NON_CORE reason: The core proteostasis role is ESCRT-I endosomal cargo sorting; this localization is secondary or broad. additional_reference_ids: *id007 supported_by: *id008 - term: id: GO:0005737 label: cytoplasm evidence_type: IEA original_reference_id: GO_REF:0000120 qualifier: located_in review: summary: cytoplasm is supported as a localization/context row but is not the core MVB12A function. action: KEEP_AS_NON_CORE reason: The core proteostasis role is ESCRT-I endosomal cargo sorting; this localization is secondary or broad. additional_reference_ids: *id007 supported_by: *id008 - term: id: GO:0005768 label: endosome evidence_type: IEA original_reference_id: GO_REF:0000044 qualifier: located_in review: summary: endosome localization is supported and relevant to MVB12A/ESCRT-I function. action: ACCEPT reason: MVB12A is an ESCRT-I subunit associated with endosomes/late-endosome membrane and endosomal cargo sorting. additional_reference_ids: &id009 - file:human/MVB12A/MVB12A-uniprot.txt - PMID:22232651 - file:human/MVB12A/MVB12A-notes.md supported_by: &id010 - &id026 reference_id: file:human/MVB12A/MVB12A-uniprot.txt supporting_text: Endosome - &id027 reference_id: file:human/MVB12A/MVB12A-uniprot.txt supporting_text: Late endosome membrane - &id028 reference_id: PMID:22232651 supporting_text: function both in protein transport at endosomes - term: id: GO:0005813 label: centrosome evidence_type: IEA original_reference_id: GO_REF:0000044 qualifier: located_in review: summary: centrosome is supported as a localization/context row but is not the core MVB12A function. action: KEEP_AS_NON_CORE reason: The core proteostasis role is ESCRT-I endosomal cargo sorting; this localization is secondary or broad. additional_reference_ids: *id007 supported_by: *id008 - 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 MVB12A/ESCRT-I function. action: ACCEPT reason: MVB12A is an ESCRT-I subunit associated with endosomes/late-endosome membrane and endosomal cargo sorting. additional_reference_ids: *id009 supported_by: *id010 - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:28514442 qualifier: enables review: summary: Protein binding is too generic to represent MVB12A function. action: MARK_AS_OVER_ANNOTATED reason: The informative annotations are ESCRT-I complex membership, SH3-domain binding context, ubiquitin binding, and phospholipid binding, not generic protein binding from broad interaction screens. proposed_replacement_terms: - id: GO:0000813 label: ESCRT I complex additional_reference_ids: &id011 - PMID:28514442 - PMID:32296183 - PMID:33961781 - file:human/MVB12A/MVB12A-notes.md supported_by: &id012 - reference_id: file:human/MVB12A/MVB12A-notes.md supporting_text: Generic `protein binding` rows should be replaced where possible - 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 MVB12A function. action: MARK_AS_OVER_ANNOTATED reason: The informative annotations are ESCRT-I complex membership, SH3-domain binding context, ubiquitin binding, and phospholipid binding, not generic protein binding from broad interaction screens. proposed_replacement_terms: - id: GO:0000813 label: ESCRT I complex additional_reference_ids: *id011 supported_by: *id012 - 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 MVB12A function. action: MARK_AS_OVER_ANNOTATED reason: The informative annotations are ESCRT-I complex membership, SH3-domain binding context, ubiquitin binding, and phospholipid binding, not generic protein binding from broad interaction screens. proposed_replacement_terms: - id: GO:0000813 label: ESCRT I complex additional_reference_ids: *id011 supported_by: *id012 - 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 MVB12A cellular-component annotation. action: ACCEPT reason: MVB12A is a metazoan fourth subunit of ESCRT-I and is directly supported by ESCRT-I composition and structural studies. additional_reference_ids: *id005 supported_by: *id006 - term: id: GO:0000813 label: ESCRT I complex evidence_type: IPI original_reference_id: PMID:32424346 qualifier: part_of review: summary: ESCRT-I complex membership is the central MVB12A cellular-component annotation. action: ACCEPT reason: MVB12A is a metazoan fourth subunit of ESCRT-I and is directly supported by ESCRT-I composition and structural studies. additional_reference_ids: *id005 supported_by: *id006 - 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 MVB12A/ESCRT-I function. action: ACCEPT reason: MVB12A is an ESCRT-I subunit associated with endosomes/late-endosome membrane and endosomal cargo sorting. additional_reference_ids: *id009 supported_by: *id010 - 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 MVB12A/ESCRT-I endosomal cargo sorting. action: ACCEPT reason: MVB12A/ESCRT-I supports ubiquitin-dependent endosomal cargo sorting, receptor down-regulation, and multivesicular body pathway transport. 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 MVB12A/ESCRT-I endosomal cargo sorting. action: ACCEPT reason: MVB12A/ESCRT-I supports ubiquitin-dependent endosomal cargo sorting, receptor down-regulation, and multivesicular body pathway transport. 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 as an ESCRT-I complex-level mechanism involving MVB12A-containing headpiece assemblies. action: ACCEPT reason: MVB12A is directly present in the structural ESCRT-I headpiece used to support ESCRT-I filament/scaffolding behavior, although the perturbation assay targeted VPS28. additional_reference_ids: - PMID:32424346 - PMID:20588296 - file:human/MVB12A/MVB12A-notes.md - file:human/MVB12A/MVB12A-deep-research-falcon.md supported_by: - &id023 reference_id: PMID:32424346 supporting_text: comprising TSG101-VPS28-VPS37B-MVB12A - &id024 reference_id: PMID:32424346 supporting_text: 22-amino acid fragment of MVB12A - &id025 reference_id: PMID:32424346 supporting_text: ESCRT-I is not merely a bridging adaptor - reference_id: file:human/MVB12A/MVB12A-deep-research-falcon.md supporting_text: MVB12A is not merely a passive adaptor but participates in active scaffolding for membrane remodeling - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:18005716 qualifier: enables review: summary: Protein binding from ESCRT-I reconstitution should be replaced by ESCRT-I complex membership. action: MODIFY reason: The interaction evidence supports complex membership rather than generic protein binding. proposed_replacement_terms: - id: GO:0000813 label: ESCRT I complex additional_reference_ids: *id005 supported_by: *id006 - term: id: GO:0046755 label: viral budding evidence_type: IMP original_reference_id: PMID:18005716 qualifier: involved_in review: summary: viral budding is directly supported but is a non-core host-pathogen context for this review. action: KEEP_AS_NON_CORE reason: MVB12A/MVB12 subunits regulate HIV/viral budding and maturation, but the core cellular proteostasis role is endosomal ESCRT-I cargo sorting. additional_reference_ids: *id003 supported_by: *id004 - 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 MVB12A/ESCRT-I function. action: ACCEPT reason: MVB12A is an ESCRT-I subunit associated with endosomes/late-endosome membrane and endosomal cargo sorting. additional_reference_ids: *id009 supported_by: *id010 - 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 MVB12A/ESCRT-I function. action: ACCEPT reason: MVB12A is an ESCRT-I subunit associated with endosomes/late-endosome membrane and endosomal cargo sorting. additional_reference_ids: *id009 supported_by: *id010 - 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 MVB12A/ESCRT-I function. action: ACCEPT reason: MVB12A is an ESCRT-I subunit associated with endosomes/late-endosome membrane and endosomal cargo sorting. additional_reference_ids: *id009 supported_by: *id010 - 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 MVB12A/ESCRT-I function. action: ACCEPT reason: MVB12A is an ESCRT-I subunit associated with endosomes/late-endosome membrane and endosomal cargo sorting. additional_reference_ids: *id009 supported_by: *id010 - 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 MVB12A/ESCRT-I function. action: ACCEPT reason: MVB12A is an ESCRT-I subunit associated with endosomes/late-endosome membrane and endosomal cargo sorting. additional_reference_ids: *id009 supported_by: *id010 - term: id: GO:0016236 label: macroautophagy evidence_type: TAS original_reference_id: PMID:20588296 qualifier: involved_in review: summary: Macroautophagy is over-annotated for MVB12A as written. action: MARK_AS_OVER_ANNOTATED reason: The broad ESCRT/autophagy review and VPS28-interface structural assay do not directly establish MVB12A as a core macroautophagy or phagophore-closure factor. proposed_replacement_terms: - id: GO:0000813 label: ESCRT I complex - id: GO:0090148 label: membrane fission additional_reference_ids: - PMID:20588296 - PMID:31519728 - PMID:32424346 - file:human/MVB12A/MVB12A-notes.md supported_by: - reference_id: PMID:20588296 supporting_text: viral budding, cytokinesis and, probably, autophagy - reference_id: PMID:20588296 supporting_text: direct neck closure reaction in autophagy - reference_id: PMID:31519728 supporting_text: identify the ESCRT-I subunit VPS37A as a critical component - reference_id: PMID:31519728 supporting_text: required for autophagosome completion - reference_id: PMID:32424346 supporting_text: Mutation of VPS28 helical interface residues blocks filament formation - 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 MVB12A cellular-component annotation. action: ACCEPT reason: MVB12A is a metazoan fourth subunit of ESCRT-I and is directly supported by ESCRT-I composition and structural studies. additional_reference_ids: *id005 supported_by: *id006 - 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 MVB12A/ESCRT-I endosomal cargo sorting. action: ACCEPT reason: MVB12A/ESCRT-I supports ubiquitin-dependent endosomal cargo sorting, receptor down-regulation, and multivesicular body pathway transport. 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 directly supported but is a non-core host-pathogen context for this review. action: KEEP_AS_NON_CORE reason: MVB12A/MVB12 subunits regulate HIV/viral budding and maturation, but the core cellular proteostasis role is endosomal ESCRT-I cargo sorting. additional_reference_ids: *id003 supported_by: *id004 - term: id: GO:0019075 label: virus maturation evidence_type: IMP original_reference_id: PMID:18005716 qualifier: involved_in review: summary: virus maturation is directly supported but is a non-core host-pathogen context for this review. action: KEEP_AS_NON_CORE reason: MVB12A/MVB12 subunits regulate HIV/viral budding and maturation, but the core cellular proteostasis role is endosomal ESCRT-I cargo sorting. additional_reference_ids: *id003 supported_by: *id004 - 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 MVB12A cellular-component annotation. action: ACCEPT reason: MVB12A is a metazoan fourth subunit of ESCRT-I and is directly supported by ESCRT-I composition and structural studies. additional_reference_ids: *id005 supported_by: *id006 - term: id: GO:0005813 label: centrosome evidence_type: IDA original_reference_id: PMID:18005716 qualifier: located_in review: summary: centrosome is supported as a localization/context row but is not the core MVB12A function. action: KEEP_AS_NON_CORE reason: The core proteostasis role is ESCRT-I endosomal cargo sorting; this localization is secondary or broad. additional_reference_ids: *id007 supported_by: *id008 - term: id: GO:0070062 label: extracellular exosome evidence_type: HDA original_reference_id: PMID:23533145 qualifier: located_in review: summary: extracellular exosome is supported as a localization/context row but is not the core MVB12A function. action: KEEP_AS_NON_CORE reason: The core proteostasis role is ESCRT-I endosomal cargo sorting; this localization is secondary or broad. additional_reference_ids: *id007 supported_by: *id008 - 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 MVB12A cellular-component annotation. action: ACCEPT reason: MVB12A is a metazoan fourth subunit of ESCRT-I and is directly supported by ESCRT-I composition and structural studies. additional_reference_ids: *id005 supported_by: *id006 - term: id: GO:0000813 label: ESCRT I complex evidence_type: IDA original_reference_id: PMID:22232651 qualifier: part_of review: summary: ESCRT-I complex membership is the central MVB12A cellular-component annotation. action: ACCEPT reason: MVB12A is a metazoan fourth subunit of ESCRT-I and is directly supported by ESCRT-I composition and structural studies. additional_reference_ids: *id005 supported_by: *id006 - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:20654576 qualifier: enables review: summary: Protein binding should be replaced by the more informative SH3 domain binding context. action: MODIFY reason: MVB12A/CFBP binds CD2AP/CIN85 SH3-domain proteins through a proline-rich motif regulated by Tyr204 phosphorylation. proposed_replacement_terms: - id: GO:0017124 label: SH3 domain binding additional_reference_ids: - PMID:16895919 - PMID:20654576 - file:human/MVB12A/MVB12A-uniprot.txt - file:human/MVB12A/MVB12A-notes.md supported_by: - reference_id: PMID:16895919 supporting_text: CIN85/CD2AP family was identified as a binding partner - reference_id: PMID:16895919 supporting_text: recognized by one of the three Src-homology 3 domains - reference_id: PMID:20654576 supporting_text: affects binding to CD2AP - term: id: GO:0005829 label: cytosol evidence_type: IDA original_reference_id: PMID:20654576 qualifier: located_in review: summary: cytosol is supported as a localization/context row but is not the core MVB12A function. action: KEEP_AS_NON_CORE reason: The core proteostasis role is ESCRT-I endosomal cargo sorting; this localization is secondary or broad. additional_reference_ids: *id007 supported_by: *id008 - term: id: GO:0008289 label: lipid binding evidence_type: IMP original_reference_id: PMID:22232651 qualifier: enables review: summary: Lipid binding is correct but should be made more specific. action: MODIFY reason: MVB12A/MVB12B MABP domains bind acidic phospholipid-containing liposomes, so phospholipid binding is the more informative MF term. proposed_replacement_terms: - id: GO:0005543 label: phospholipid binding additional_reference_ids: - PMID:22232651 - file:human/MVB12A/MVB12A-notes.md - file:human/MVB12A/MVB12A-deep-research-falcon.md supported_by: - reference_id: PMID:22232651 supporting_text: MABP domains of the MVB12A and B subunits - reference_id: PMID:22232651 supporting_text: bind in vitro to liposomes containing acidic lipids - reference_id: PMID:22232651 supporting_text: coincidence detector for acidic phospholipids and protein ligands - reference_id: file:human/MVB12A/MVB12A-deep-research-falcon.md supporting_text: binds to acidic liposomes containing anionic lipids - term: id: GO:0031982 label: vesicle evidence_type: IDA original_reference_id: PMID:20654576 qualifier: located_in review: summary: vesicle is supported as a localization/context row but is not the core MVB12A function. action: KEEP_AS_NON_CORE reason: The core proteostasis role is ESCRT-I endosomal cargo sorting; this localization is secondary or broad. additional_reference_ids: *id007 supported_by: *id008 - term: id: GO:0042058 label: regulation of epidermal growth factor receptor signaling pathway evidence_type: IMP original_reference_id: PMID:20654576 qualifier: involved_in review: summary: EGFR signaling regulation is supported as a substrate-specific MVB12A context. action: KEEP_AS_NON_CORE reason: MVB12A affects EGFR down-regulation through CD2AP/CIN85 and ESCRT-I, but EGFR signaling is a cargo/context-specific consequence rather than the core function. additional_reference_ids: *id013 supported_by: *id014 - term: id: GO:0043130 label: ubiquitin binding evidence_type: IMP original_reference_id: PMID:20654576 qualifier: enables review: summary: Ubiquitin binding is plausible from the GOA/UniProt row but cannot be confirmed from the cached abstract. action: UNDECIDED reason: The row cites PMID:20654576, but the cached abstract available locally does not expose the underlying ubiquitin-binding experiment. Verify full text before accepting or replacing this MF annotation. additional_reference_ids: - PMID:20654576 - file:human/MVB12A/MVB12A-notes.md supported_by: - reference_id: file:human/MVB12A/MVB12A-notes.md supporting_text: that row should remain undecided pending full-text confirmation - 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 MVB12A/ESCRT-I endosomal cargo sorting. action: ACCEPT reason: MVB12A/ESCRT-I supports ubiquitin-dependent endosomal cargo sorting, receptor down-regulation, and multivesicular body pathway transport. additional_reference_ids: *id001 supported_by: *id002 - term: id: GO:0070062 label: extracellular exosome evidence_type: HDA original_reference_id: PMID:19056867 qualifier: located_in review: summary: extracellular exosome is supported as a localization/context row but is not the core MVB12A function. action: KEEP_AS_NON_CORE reason: The core proteostasis role is ESCRT-I endosomal cargo sorting; this localization is secondary or broad. additional_reference_ids: *id007 supported_by: *id008 references: - id: GO_REF:0000002 title: Gene Ontology annotation through association of InterPro records with GO terms findings: [] - 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:0000120 title: Combined Automated Annotation using Multiple IEA Methods findings: [] - id: PMID:18005716 title: Identification of human MVB12 proteins as ESCRT-I subunits that function in HIV budding. findings: [] - id: PMID:19056867 title: Large-scale proteomics and phosphoproteomics of urinary exosomes. 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:22232651 title: "Structural basis for membrane targeting by the MVB12-associated \u03B2-prism domain of the human ESCRT-I MVB12 subunit." findings: [] - id: PMID:23533145 title: In-depth proteomic analyses of exosomes isolated from expressed prostatic secretions in urine. findings: [] - id: PMID:28514442 title: Architecture of the human interactome defines protein communities and disease networks. 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:33961781 title: Dual proteome-scale networks reveal cell-specific remodeling of the human interactome. 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:16895919 title: CFBP is a novel tyrosine-phosphorylated protein that might function as a regulator of CIN85/CD2AP. findings: [] - id: PMID:31519728 title: VPS37A directs ESCRT recruitment for phagophore closure. findings: [] - id: file:human/MVB12A/MVB12A-uniprot.txt title: UniProtKB record for human MVB12A findings: [] - id: file:human/MVB12A/MVB12A-notes.md title: MVB12A review notes findings: [] - id: file:human/MVB12A/MVB12A-deep-research-falcon.md title: Falcon deep research report for MVB12A findings: [] reference_review: relevance: HIGH correctness: UNVERIFIED review_notes: >- LLM-synthesized deep research report (Edison/Falcon). Useful as a structured synthesis that is consistent with the primary literature already cited in this review (Morita 2007, Audhya 2007, Boura/Hurley 2012, Flower 2020). It correctly anchors MVB12A as a structural/adapter fourth subunit of ESCRT-I (UMA domain) with an N-terminal MABP membrane-targeting domain, and it adds one genuinely new MVB12A-specific finding: the 2025 Zhang et al. study (mBio, doi:10.1128/mbio.00979-25) showing MVB12A knockdown impairs beta-coronavirus virion egress without blocking assembly. CAUTION: many statements in the report ascribe whole-ESCRT-I-complex or pan-MVB12-family functions (cytokinesis/abscission, membrane repair, autophagosome closure, exosome biogenesis, ubiquitin-dependent MVB sorting) to MVB12A by inference from the holo-complex or from the MVB12B/UBAP1 paralogs rather than from MVB12A-specific perturbation; e.g. UBAP1-, not MVB12A-, containing ESCRT-I is the one shown to be required for ubiquitin-dependent MVB sorting (Stefani 2011), and the autophagosome-closure assay perturbed VPS28, not MVB12A (Flower 2020). MVB12A-specific claims are kept anchored; holo-complex/paralog inferences are not used to upgrade annotations. Identifier and supporting-text claims have not been independently verified against the cited primary papers, hence UNVERIFIED. core_functions: - description: MVB12A is a fourth subunit of metazoan ESCRT-I complexes and helps organize MVB12A-containing TSG101-VPS28-VPS37 ESCRT-I assemblies. directly_involved_in: - id: GO:0036258 label: multivesicular body assembly - id: GO:0090148 label: membrane fission 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: - *id015 - *id016 - *id017 - *id018 - *id019 - *id020 - *id021 - *id022 - *id023 - *id024 - *id025 - *id026 - *id027 - *id028 - description: MVB12A supports endosomal sorting and down-regulation of ubiquitinated receptor cargo, including EGFR pathway cargo context. molecular_function: id: GO:0005543 label: phospholipid binding directly_involved_in: - id: GO:0032510 label: endosome to lysosome transport via multivesicular body sorting pathway - id: GO:0043162 label: ubiquitin-dependent protein catabolic process via the multivesicular body sorting pathway - id: GO:0032801 label: receptor catabolic process locations: - id: GO:0005768 label: endosome - id: GO:0010008 label: endosome membrane in_complex: id: GO:0000813 label: ESCRT I complex supported_by: - *id029 - *id030 - *id031 - *id032 - *id033 - *id034 - *id035 - *id036 - *id037 - *id038 proposed_new_terms: [] suggested_questions: - question: Should MVB12A macroautophagy annotations be retired, modified to ESCRT-I membrane fission, or kept non-core pending MVB12A-specific phagophore-closure perturbation evidence? experts: - GO autophagy editors - GO ESCRT curators - question: Should MVB12A generic protein-binding annotations be replaced by ESCRT-I complex membership, SH3 domain binding, phospholipid binding, and ubiquitin binding where the evidence supports those more specific terms? experts: - GO molecular function editors - UniProt curators suggested_experiments: - experiment_type: MVB12A-specific phagophore closure assay hypothesis: MVB12A-containing ESCRT-I assemblies contribute to ESCRT-I scaffold mechanics, but MVB12A-specific loss has not been shown to be required for phagophore closure. description: Use MVB12A knockout/rescue in HT-LC3 autophagosome closure assays, with VPS37A and VPS28 helical-interface perturbations as controls, and compare effects on EGFR MVB sorting. - experiment_type: MVB12A molecular-function refinement hypothesis: MVB12A membrane and cargo recognition is better represented by phospholipid binding, ubiquitin binding, and SH3-domain-binding contexts than generic protein binding. description: Test purified MVB12A domains for acidic phospholipid binding, ubiquitin binding, and CD2AP/CIN85 SH3-domain binding using matched mutants and rescue readouts in EGFR down-regulation assays.