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.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0000813 ESCRT I complex | IBA GO_REF:0000033 | ACCEPT | Summary: ESCRT-I complex membership is the central MVB12A cellular-component annotation. Reason: MVB12A is a metazoan fourth subunit of ESCRT-I and is directly supported by ESCRT-I composition and structural studies. Supporting Evidence: file:human/MVB12A/MVB12A-uniprot.txt Component of the ESCRT-I complex file:human/MVB12A/MVB12A-uniprot.txt which consists of TSG101, VPS28, a VPS37 file:human/MVB12A/MVB12A-uniprot.txt Interacts with TSG101 file:human/MVB12A/MVB12A-uniprot.txt Interacts with VPS28 PMID:18005716 constitute the fourth class of metazoan ESCRT-I subunits PMID:18005716 one copy of each of the four subunit types PMID:18005716 associate with the core region of the binary TSG101-VPS37 complex PMID:32424346 comprising TSG101-VPS28-VPS37B-MVB12A |
| GO:0005829 cytosol | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: cytosol is supported as a localization/context row but is not the core MVB12A function. Reason: The core proteostasis role is ESCRT-I endosomal cargo sorting; this localization is secondary or broad. Supporting Evidence: file:human/MVB12A/MVB12A-uniprot.txt Cytoplasm file:human/MVB12A/MVB12A-uniprot.txt Nucleus file:human/MVB12A/MVB12A-uniprot.txt centrosome PMID:19056867 Large-scale proteomics and phosphoproteomics of urinary exosomes PMID:23533145 In-depth proteomic analyses of exosomes |
| GO:0019075 virus maturation | IBA GO_REF:0000033 | KEEP AS NON CORE | 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). 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. Supporting Evidence: PMID:18005716 MVB12 depletion and overexpression inhibit HIV-1 infectivity PMID:18005716 aberrant virion morphologies and altered viral Gag protein processing PMID:32424346 HIV-1 release in human cells PMID:20588296 viral budding, cytokinesis and, probably, autophagy file:human/MVB12A/MVB12A-deep-research-falcon.md Knockdown of MVB12A did not affect the early stages of virion assembly, but significantly inhibited virion egress from cells file:human/MVB12A/MVB12A-deep-research-falcon.md late-acting ESCRT component in coronavirus replication |
| GO:0032510 endosome to lysosome transport via multivesicular body sorting pathway | IBA GO_REF:0000033 | ACCEPT | Summary: endosome to lysosome transport via multivesicular body sorting pathway is supported as part of MVB12A/ESCRT-I endosomal cargo sorting. Reason: MVB12A/ESCRT-I supports ubiquitin-dependent endosomal cargo sorting, receptor down-regulation, and multivesicular body pathway transport. Supporting Evidence: file:human/MVB12A/MVB12A-uniprot.txt Required for the sorting of endocytic file:human/MVB12A/MVB12A-uniprot.txt ubiquitinated cargos into multivesicular bodies PMID:18005716 plays essential roles in HIV budding and endosomal protein sorting PMID:16895919 accelerated the EGF receptor's down-regulation PMID:20654576 amounts of EGF receptor bound to ESCRT-I |
| GO:0032801 receptor catabolic process | IBA GO_REF:0000033 | ACCEPT | Summary: receptor catabolic process is supported as part of MVB12A/ESCRT-I endosomal cargo sorting. Reason: MVB12A/ESCRT-I supports ubiquitin-dependent endosomal cargo sorting, receptor down-regulation, and multivesicular body pathway transport. Supporting Evidence: file:human/MVB12A/MVB12A-uniprot.txt Required for the sorting of endocytic file:human/MVB12A/MVB12A-uniprot.txt ubiquitinated cargos into multivesicular bodies PMID:18005716 plays essential roles in HIV budding and endosomal protein sorting PMID:16895919 accelerated the EGF receptor's down-regulation PMID:20654576 amounts of EGF receptor bound to ESCRT-I |
| GO:0042058 regulation of epidermal growth factor receptor signaling pathway | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: EGFR signaling regulation is supported as a substrate-specific MVB12A context. 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. Supporting Evidence: PMID:16895919 phosphorylated at tyrosine 204 upon EGF stimulation PMID:16895919 accelerated the EGF receptor's down-regulation PMID:20654576 Tyr204 phosphorylation of MVB12A PMID:20654576 affects binding to CD2AP PMID:20654576 amounts of EGF receptor bound to ESCRT-I |
| GO:0046755 viral budding | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: viral budding is directly supported but is a non-core host-pathogen context for this review. Reason: MVB12A/MVB12 subunits regulate HIV/viral budding and maturation, but the core cellular proteostasis role is endosomal ESCRT-I cargo sorting. Supporting Evidence: PMID:18005716 MVB12 depletion and overexpression inhibit HIV-1 infectivity PMID:18005716 aberrant virion morphologies and altered viral Gag protein processing PMID:32424346 HIV-1 release in human cells PMID:20588296 viral budding, cytokinesis and, probably, autophagy file:human/MVB12A/MVB12A-deep-research-falcon.md Knockdown of MVB12A did not affect the early stages of virion assembly, but significantly inhibited virion egress from cells file:human/MVB12A/MVB12A-deep-research-falcon.md late-acting ESCRT component in coronavirus replication |
| GO:0000813 ESCRT I complex | IEA GO_REF:0000002 | ACCEPT | Summary: ESCRT-I complex membership is the central MVB12A cellular-component annotation. Reason: MVB12A is a metazoan fourth subunit of ESCRT-I and is directly supported by ESCRT-I composition and structural studies. Supporting Evidence: file:human/MVB12A/MVB12A-uniprot.txt Component of the ESCRT-I complex file:human/MVB12A/MVB12A-uniprot.txt which consists of TSG101, VPS28, a VPS37 file:human/MVB12A/MVB12A-uniprot.txt Interacts with TSG101 file:human/MVB12A/MVB12A-uniprot.txt Interacts with VPS28 PMID:18005716 constitute the fourth class of metazoan ESCRT-I subunits PMID:18005716 one copy of each of the four subunit types PMID:18005716 associate with the core region of the binary TSG101-VPS37 complex PMID:32424346 comprising TSG101-VPS28-VPS37B-MVB12A |
| GO:0005634 nucleus | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: nucleus is supported as a localization/context row but is not the core MVB12A function. Reason: The core proteostasis role is ESCRT-I endosomal cargo sorting; this localization is secondary or broad. Supporting Evidence: file:human/MVB12A/MVB12A-uniprot.txt Cytoplasm file:human/MVB12A/MVB12A-uniprot.txt Nucleus file:human/MVB12A/MVB12A-uniprot.txt centrosome PMID:19056867 Large-scale proteomics and phosphoproteomics of urinary exosomes PMID:23533145 In-depth proteomic analyses of exosomes |
| GO:0005737 cytoplasm | IEA GO_REF:0000120 | KEEP AS NON CORE | Summary: cytoplasm is supported as a localization/context row but is not the core MVB12A function. Reason: The core proteostasis role is ESCRT-I endosomal cargo sorting; this localization is secondary or broad. Supporting Evidence: file:human/MVB12A/MVB12A-uniprot.txt Cytoplasm file:human/MVB12A/MVB12A-uniprot.txt Nucleus file:human/MVB12A/MVB12A-uniprot.txt centrosome PMID:19056867 Large-scale proteomics and phosphoproteomics of urinary exosomes PMID:23533145 In-depth proteomic analyses of exosomes |
| GO:0005768 endosome | IEA GO_REF:0000044 | ACCEPT | Summary: endosome localization is supported and relevant to MVB12A/ESCRT-I function. Reason: MVB12A is an ESCRT-I subunit associated with endosomes/late-endosome membrane and endosomal cargo sorting. Supporting Evidence: file:human/MVB12A/MVB12A-uniprot.txt Endosome file:human/MVB12A/MVB12A-uniprot.txt Late endosome membrane PMID:22232651 function both in protein transport at endosomes |
| GO:0005813 centrosome | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: centrosome is supported as a localization/context row but is not the core MVB12A function. Reason: The core proteostasis role is ESCRT-I endosomal cargo sorting; this localization is secondary or broad. Supporting Evidence: file:human/MVB12A/MVB12A-uniprot.txt Cytoplasm file:human/MVB12A/MVB12A-uniprot.txt Nucleus file:human/MVB12A/MVB12A-uniprot.txt centrosome PMID:19056867 Large-scale proteomics and phosphoproteomics of urinary exosomes PMID:23533145 In-depth proteomic analyses of exosomes |
| GO:0031902 late endosome membrane | IEA GO_REF:0000044 | ACCEPT | Summary: late endosome membrane localization is supported and relevant to MVB12A/ESCRT-I function. Reason: MVB12A is an ESCRT-I subunit associated with endosomes/late-endosome membrane and endosomal cargo sorting. Supporting Evidence: file:human/MVB12A/MVB12A-uniprot.txt Endosome file:human/MVB12A/MVB12A-uniprot.txt Late endosome membrane PMID:22232651 function both in protein transport at endosomes |
| GO:0005515 protein binding | IPI PMID:28514442 Architecture of the human interactome defines protein commun... | MARK AS OVER ANNOTATED | Summary: Protein binding is too generic to represent MVB12A function. 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 replacements: ESCRT I complex Supporting Evidence: file:human/MVB12A/MVB12A-notes.md Generic `protein binding` rows should be replaced where possible |
| 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 MVB12A function. 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 replacements: ESCRT I complex Supporting Evidence: file:human/MVB12A/MVB12A-notes.md Generic `protein binding` rows should be replaced where possible |
| 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 MVB12A function. 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 replacements: ESCRT I complex Supporting Evidence: file:human/MVB12A/MVB12A-notes.md Generic `protein binding` rows should be replaced where possible |
| 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 MVB12A cellular-component annotation. Reason: MVB12A is a metazoan fourth subunit of ESCRT-I and is directly supported by ESCRT-I composition and structural studies. Supporting Evidence: file:human/MVB12A/MVB12A-uniprot.txt Component of the ESCRT-I complex file:human/MVB12A/MVB12A-uniprot.txt which consists of TSG101, VPS28, a VPS37 file:human/MVB12A/MVB12A-uniprot.txt Interacts with TSG101 file:human/MVB12A/MVB12A-uniprot.txt Interacts with VPS28 PMID:18005716 constitute the fourth class of metazoan ESCRT-I subunits PMID:18005716 one copy of each of the four subunit types PMID:18005716 associate with the core region of the binary TSG101-VPS37 complex PMID:32424346 comprising TSG101-VPS28-VPS37B-MVB12A |
| GO:0000813 ESCRT I complex | IPI PMID:32424346 A helical assembly of human ESCRT-I scaffolds reverse-topolo... | ACCEPT | Summary: ESCRT-I complex membership is the central MVB12A cellular-component annotation. Reason: MVB12A is a metazoan fourth subunit of ESCRT-I and is directly supported by ESCRT-I composition and structural studies. Supporting Evidence: file:human/MVB12A/MVB12A-uniprot.txt Component of the ESCRT-I complex file:human/MVB12A/MVB12A-uniprot.txt which consists of TSG101, VPS28, a VPS37 file:human/MVB12A/MVB12A-uniprot.txt Interacts with TSG101 file:human/MVB12A/MVB12A-uniprot.txt Interacts with VPS28 PMID:18005716 constitute the fourth class of metazoan ESCRT-I subunits PMID:18005716 one copy of each of the four subunit types PMID:18005716 associate with the core region of the binary TSG101-VPS37 complex PMID:32424346 comprising TSG101-VPS28-VPS37B-MVB12A |
| 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 MVB12A/ESCRT-I function. Reason: MVB12A is an ESCRT-I subunit associated with endosomes/late-endosome membrane and endosomal cargo sorting. Supporting Evidence: file:human/MVB12A/MVB12A-uniprot.txt Endosome file:human/MVB12A/MVB12A-uniprot.txt Late endosome membrane PMID:22232651 function both in protein transport at 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 MVB12A/ESCRT-I endosomal cargo sorting. Reason: MVB12A/ESCRT-I supports ubiquitin-dependent endosomal cargo sorting, receptor down-regulation, and multivesicular body pathway transport. Supporting Evidence: file:human/MVB12A/MVB12A-uniprot.txt Required for the sorting of endocytic file:human/MVB12A/MVB12A-uniprot.txt ubiquitinated cargos into multivesicular bodies PMID:18005716 plays essential roles in HIV budding and endosomal protein sorting PMID:16895919 accelerated the EGF receptor's down-regulation PMID:20654576 amounts of EGF receptor bound to ESCRT-I |
| 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 MVB12A/ESCRT-I endosomal cargo sorting. Reason: MVB12A/ESCRT-I supports ubiquitin-dependent endosomal cargo sorting, receptor down-regulation, and multivesicular body pathway transport. Supporting Evidence: file:human/MVB12A/MVB12A-uniprot.txt Required for the sorting of endocytic file:human/MVB12A/MVB12A-uniprot.txt ubiquitinated cargos into multivesicular bodies PMID:18005716 plays essential roles in HIV budding and endosomal protein sorting PMID:16895919 accelerated the EGF receptor's down-regulation PMID:20654576 amounts of EGF receptor bound to ESCRT-I |
| GO:0090148 membrane fission | NAS PMID:32424346 A helical assembly of human ESCRT-I scaffolds reverse-topolo... | ACCEPT | Summary: Membrane fission is supported as an ESCRT-I complex-level mechanism involving MVB12A-containing headpiece assemblies. 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. Supporting Evidence: PMID:32424346 comprising TSG101-VPS28-VPS37B-MVB12A PMID:32424346 22-amino acid fragment of MVB12A PMID:32424346 ESCRT-I is not merely a bridging adaptor file:human/MVB12A/MVB12A-deep-research-falcon.md MVB12A is not merely a passive adaptor but participates in active scaffolding for membrane remodeling |
| GO:0005515 protein binding | IPI PMID:18005716 Identification of human MVB12 proteins as ESCRT-I subunits t... | MODIFY | Summary: Protein binding from ESCRT-I reconstitution should be replaced by ESCRT-I complex membership. Reason: The interaction evidence supports complex membership rather than generic protein binding. Proposed replacements: ESCRT I complex Supporting Evidence: file:human/MVB12A/MVB12A-uniprot.txt Component of the ESCRT-I complex file:human/MVB12A/MVB12A-uniprot.txt which consists of TSG101, VPS28, a VPS37 file:human/MVB12A/MVB12A-uniprot.txt Interacts with TSG101 file:human/MVB12A/MVB12A-uniprot.txt Interacts with VPS28 PMID:18005716 constitute the fourth class of metazoan ESCRT-I subunits PMID:18005716 one copy of each of the four subunit types PMID:18005716 associate with the core region of the binary TSG101-VPS37 complex PMID:32424346 comprising TSG101-VPS28-VPS37B-MVB12A |
| GO:0046755 viral budding | IMP PMID:18005716 Identification of human MVB12 proteins as ESCRT-I subunits t... | KEEP AS NON CORE | Summary: viral budding is directly supported but is a non-core host-pathogen context for this review. Reason: MVB12A/MVB12 subunits regulate HIV/viral budding and maturation, but the core cellular proteostasis role is endosomal ESCRT-I cargo sorting. Supporting Evidence: PMID:18005716 MVB12 depletion and overexpression inhibit HIV-1 infectivity PMID:18005716 aberrant virion morphologies and altered viral Gag protein processing PMID:32424346 HIV-1 release in human cells PMID:20588296 viral budding, cytokinesis and, probably, autophagy file:human/MVB12A/MVB12A-deep-research-falcon.md Knockdown of MVB12A did not affect the early stages of virion assembly, but significantly inhibited virion egress from cells file:human/MVB12A/MVB12A-deep-research-falcon.md late-acting ESCRT component in coronavirus replication |
| GO:0010008 endosome membrane | TAS Reactome:R-HSA-184269 | ACCEPT | Summary: endosome membrane localization is supported and relevant to MVB12A/ESCRT-I function. Reason: MVB12A is an ESCRT-I subunit associated with endosomes/late-endosome membrane and endosomal cargo sorting. Supporting Evidence: file:human/MVB12A/MVB12A-uniprot.txt Endosome file:human/MVB12A/MVB12A-uniprot.txt Late endosome membrane PMID:22232651 function both in protein transport at endosomes |
| GO:0010008 endosome membrane | TAS Reactome:R-HSA-3149434 | ACCEPT | Summary: endosome membrane localization is supported and relevant to MVB12A/ESCRT-I function. Reason: MVB12A is an ESCRT-I subunit associated with endosomes/late-endosome membrane and endosomal cargo sorting. Supporting Evidence: file:human/MVB12A/MVB12A-uniprot.txt Endosome file:human/MVB12A/MVB12A-uniprot.txt Late endosome membrane PMID:22232651 function both in protein transport at endosomes |
| GO:0010008 endosome membrane | TAS Reactome:R-HSA-3159232 | ACCEPT | Summary: endosome membrane localization is supported and relevant to MVB12A/ESCRT-I function. Reason: MVB12A is an ESCRT-I subunit associated with endosomes/late-endosome membrane and endosomal cargo sorting. Supporting Evidence: file:human/MVB12A/MVB12A-uniprot.txt Endosome file:human/MVB12A/MVB12A-uniprot.txt Late endosome membrane PMID:22232651 function both in protein transport at endosomes |
| GO:0010008 endosome membrane | TAS Reactome:R-HSA-917696 | ACCEPT | Summary: endosome membrane localization is supported and relevant to MVB12A/ESCRT-I function. Reason: MVB12A is an ESCRT-I subunit associated with endosomes/late-endosome membrane and endosomal cargo sorting. Supporting Evidence: file:human/MVB12A/MVB12A-uniprot.txt Endosome file:human/MVB12A/MVB12A-uniprot.txt Late endosome membrane PMID:22232651 function both in protein transport at endosomes |
| GO:0010008 endosome membrane | TAS Reactome:R-HSA-917730 | ACCEPT | Summary: endosome membrane localization is supported and relevant to MVB12A/ESCRT-I function. Reason: MVB12A is an ESCRT-I subunit associated with endosomes/late-endosome membrane and endosomal cargo sorting. Supporting Evidence: file:human/MVB12A/MVB12A-uniprot.txt Endosome file:human/MVB12A/MVB12A-uniprot.txt Late endosome membrane PMID:22232651 function both in protein transport at endosomes |
| GO:0016236 macroautophagy | TAS PMID:20588296 Membrane budding and scission by the ESCRT machinery: it's a... | MARK AS OVER ANNOTATED | Summary: Macroautophagy is over-annotated for MVB12A as written. 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 replacements: ESCRT I complex membrane fission Supporting Evidence: PMID:20588296 viral budding, cytokinesis and, probably, autophagy PMID:20588296 direct neck closure reaction in autophagy PMID:31519728 identify the ESCRT-I subunit VPS37A as a critical component PMID:31519728 required for autophagosome completion PMID:32424346 Mutation of VPS28 helical interface residues blocks filament formation |
| 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 MVB12A cellular-component annotation. Reason: MVB12A is a metazoan fourth subunit of ESCRT-I and is directly supported by ESCRT-I composition and structural studies. Supporting Evidence: file:human/MVB12A/MVB12A-uniprot.txt Component of the ESCRT-I complex file:human/MVB12A/MVB12A-uniprot.txt which consists of TSG101, VPS28, a VPS37 file:human/MVB12A/MVB12A-uniprot.txt Interacts with TSG101 file:human/MVB12A/MVB12A-uniprot.txt Interacts with VPS28 PMID:18005716 constitute the fourth class of metazoan ESCRT-I subunits PMID:18005716 one copy of each of the four subunit types PMID:18005716 associate with the core region of the binary TSG101-VPS37 complex PMID:32424346 comprising TSG101-VPS28-VPS37B-MVB12A |
| 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 MVB12A/ESCRT-I endosomal cargo sorting. Reason: MVB12A/ESCRT-I supports ubiquitin-dependent endosomal cargo sorting, receptor down-regulation, and multivesicular body pathway transport. Supporting Evidence: file:human/MVB12A/MVB12A-uniprot.txt Required for the sorting of endocytic file:human/MVB12A/MVB12A-uniprot.txt ubiquitinated cargos into multivesicular bodies PMID:18005716 plays essential roles in HIV budding and endosomal protein sorting PMID:16895919 accelerated the EGF receptor's down-regulation PMID:20654576 amounts of EGF receptor bound to ESCRT-I |
| 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 directly supported but is a non-core host-pathogen context for this review. Reason: MVB12A/MVB12 subunits regulate HIV/viral budding and maturation, but the core cellular proteostasis role is endosomal ESCRT-I cargo sorting. Supporting Evidence: PMID:18005716 MVB12 depletion and overexpression inhibit HIV-1 infectivity PMID:18005716 aberrant virion morphologies and altered viral Gag protein processing PMID:32424346 HIV-1 release in human cells PMID:20588296 viral budding, cytokinesis and, probably, autophagy file:human/MVB12A/MVB12A-deep-research-falcon.md Knockdown of MVB12A did not affect the early stages of virion assembly, but significantly inhibited virion egress from cells file:human/MVB12A/MVB12A-deep-research-falcon.md late-acting ESCRT component in coronavirus replication |
| GO:0019075 virus maturation | IMP PMID:18005716 Identification of human MVB12 proteins as ESCRT-I subunits t... | KEEP AS NON CORE | Summary: virus maturation is directly supported but is a non-core host-pathogen context for this review. Reason: MVB12A/MVB12 subunits regulate HIV/viral budding and maturation, but the core cellular proteostasis role is endosomal ESCRT-I cargo sorting. Supporting Evidence: PMID:18005716 MVB12 depletion and overexpression inhibit HIV-1 infectivity PMID:18005716 aberrant virion morphologies and altered viral Gag protein processing PMID:32424346 HIV-1 release in human cells PMID:20588296 viral budding, cytokinesis and, probably, autophagy file:human/MVB12A/MVB12A-deep-research-falcon.md Knockdown of MVB12A did not affect the early stages of virion assembly, but significantly inhibited virion egress from cells file:human/MVB12A/MVB12A-deep-research-falcon.md late-acting ESCRT component in coronavirus replication |
| 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 MVB12A cellular-component annotation. Reason: MVB12A is a metazoan fourth subunit of ESCRT-I and is directly supported by ESCRT-I composition and structural studies. Supporting Evidence: file:human/MVB12A/MVB12A-uniprot.txt Component of the ESCRT-I complex file:human/MVB12A/MVB12A-uniprot.txt which consists of TSG101, VPS28, a VPS37 file:human/MVB12A/MVB12A-uniprot.txt Interacts with TSG101 file:human/MVB12A/MVB12A-uniprot.txt Interacts with VPS28 PMID:18005716 constitute the fourth class of metazoan ESCRT-I subunits PMID:18005716 one copy of each of the four subunit types PMID:18005716 associate with the core region of the binary TSG101-VPS37 complex PMID:32424346 comprising TSG101-VPS28-VPS37B-MVB12A |
| GO:0005813 centrosome | IDA PMID:18005716 Identification of human MVB12 proteins as ESCRT-I subunits t... | KEEP AS NON CORE | Summary: centrosome is supported as a localization/context row but is not the core MVB12A function. Reason: The core proteostasis role is ESCRT-I endosomal cargo sorting; this localization is secondary or broad. Supporting Evidence: file:human/MVB12A/MVB12A-uniprot.txt Cytoplasm file:human/MVB12A/MVB12A-uniprot.txt Nucleus file:human/MVB12A/MVB12A-uniprot.txt centrosome PMID:19056867 Large-scale proteomics and phosphoproteomics of urinary exosomes PMID:23533145 In-depth proteomic analyses of exosomes |
| GO:0070062 extracellular exosome | HDA PMID:23533145 In-depth proteomic analyses of exosomes isolated from expres... | KEEP AS NON CORE | Summary: extracellular exosome is supported as a localization/context row but is not the core MVB12A function. Reason: The core proteostasis role is ESCRT-I endosomal cargo sorting; this localization is secondary or broad. Supporting Evidence: file:human/MVB12A/MVB12A-uniprot.txt Cytoplasm file:human/MVB12A/MVB12A-uniprot.txt Nucleus file:human/MVB12A/MVB12A-uniprot.txt centrosome PMID:19056867 Large-scale proteomics and phosphoproteomics of urinary exosomes PMID:23533145 In-depth proteomic analyses of exosomes |
| 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 MVB12A cellular-component annotation. Reason: MVB12A is a metazoan fourth subunit of ESCRT-I and is directly supported by ESCRT-I composition and structural studies. Supporting Evidence: file:human/MVB12A/MVB12A-uniprot.txt Component of the ESCRT-I complex file:human/MVB12A/MVB12A-uniprot.txt which consists of TSG101, VPS28, a VPS37 file:human/MVB12A/MVB12A-uniprot.txt Interacts with TSG101 file:human/MVB12A/MVB12A-uniprot.txt Interacts with VPS28 PMID:18005716 constitute the fourth class of metazoan ESCRT-I subunits PMID:18005716 one copy of each of the four subunit types PMID:18005716 associate with the core region of the binary TSG101-VPS37 complex PMID:32424346 comprising TSG101-VPS28-VPS37B-MVB12A |
| GO:0000813 ESCRT I complex | IDA PMID:22232651 Structural basis for membrane targeting by the MVB12-associa... | ACCEPT | Summary: ESCRT-I complex membership is the central MVB12A cellular-component annotation. Reason: MVB12A is a metazoan fourth subunit of ESCRT-I and is directly supported by ESCRT-I composition and structural studies. Supporting Evidence: file:human/MVB12A/MVB12A-uniprot.txt Component of the ESCRT-I complex file:human/MVB12A/MVB12A-uniprot.txt which consists of TSG101, VPS28, a VPS37 file:human/MVB12A/MVB12A-uniprot.txt Interacts with TSG101 file:human/MVB12A/MVB12A-uniprot.txt Interacts with VPS28 PMID:18005716 constitute the fourth class of metazoan ESCRT-I subunits PMID:18005716 one copy of each of the four subunit types PMID:18005716 associate with the core region of the binary TSG101-VPS37 complex PMID:32424346 comprising TSG101-VPS28-VPS37B-MVB12A |
| GO:0005515 protein binding | IPI PMID:20654576 Distinct functions of human MVB12A and MVB12B in the ESCRT-I... | MODIFY | Summary: Protein binding should be replaced by the more informative SH3 domain binding context. Reason: MVB12A/CFBP binds CD2AP/CIN85 SH3-domain proteins through a proline-rich motif regulated by Tyr204 phosphorylation. Proposed replacements: SH3 domain binding Supporting Evidence: PMID:16895919 CIN85/CD2AP family was identified as a binding partner PMID:16895919 recognized by one of the three Src-homology 3 domains PMID:20654576 affects binding to CD2AP |
| GO:0005829 cytosol | IDA PMID:20654576 Distinct functions of human MVB12A and MVB12B in the ESCRT-I... | KEEP AS NON CORE | Summary: cytosol is supported as a localization/context row but is not the core MVB12A function. Reason: The core proteostasis role is ESCRT-I endosomal cargo sorting; this localization is secondary or broad. Supporting Evidence: file:human/MVB12A/MVB12A-uniprot.txt Cytoplasm file:human/MVB12A/MVB12A-uniprot.txt Nucleus file:human/MVB12A/MVB12A-uniprot.txt centrosome PMID:19056867 Large-scale proteomics and phosphoproteomics of urinary exosomes PMID:23533145 In-depth proteomic analyses of exosomes |
| GO:0008289 lipid binding | IMP PMID:22232651 Structural basis for membrane targeting by the MVB12-associa... | MODIFY | Summary: Lipid binding is correct but should be made more specific. Reason: MVB12A/MVB12B MABP domains bind acidic phospholipid-containing liposomes, so phospholipid binding is the more informative MF term. Proposed replacements: phospholipid binding Supporting Evidence: PMID:22232651 MABP domains of the MVB12A and B subunits PMID:22232651 bind in vitro to liposomes containing acidic lipids PMID:22232651 coincidence detector for acidic phospholipids and protein ligands file:human/MVB12A/MVB12A-deep-research-falcon.md binds to acidic liposomes containing anionic lipids |
| GO:0031982 vesicle | IDA PMID:20654576 Distinct functions of human MVB12A and MVB12B in the ESCRT-I... | KEEP AS NON CORE | Summary: vesicle is supported as a localization/context row but is not the core MVB12A function. Reason: The core proteostasis role is ESCRT-I endosomal cargo sorting; this localization is secondary or broad. Supporting Evidence: file:human/MVB12A/MVB12A-uniprot.txt Cytoplasm file:human/MVB12A/MVB12A-uniprot.txt Nucleus file:human/MVB12A/MVB12A-uniprot.txt centrosome PMID:19056867 Large-scale proteomics and phosphoproteomics of urinary exosomes PMID:23533145 In-depth proteomic analyses of exosomes |
| GO:0042058 regulation of epidermal growth factor receptor signaling pathway | IMP PMID:20654576 Distinct functions of human MVB12A and MVB12B in the ESCRT-I... | KEEP AS NON CORE | Summary: EGFR signaling regulation is supported as a substrate-specific MVB12A context. 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. Supporting Evidence: PMID:16895919 phosphorylated at tyrosine 204 upon EGF stimulation PMID:16895919 accelerated the EGF receptor's down-regulation PMID:20654576 Tyr204 phosphorylation of MVB12A PMID:20654576 affects binding to CD2AP PMID:20654576 amounts of EGF receptor bound to ESCRT-I |
| GO:0043130 ubiquitin binding | IMP PMID:20654576 Distinct functions of human MVB12A and MVB12B in the ESCRT-I... | UNDECIDED | Summary: Ubiquitin binding is plausible from the GOA/UniProt row but cannot be confirmed from the cached abstract. 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. Supporting Evidence: file:human/MVB12A/MVB12A-notes.md that row should remain undecided pending full-text confirmation |
| 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 MVB12A/ESCRT-I endosomal cargo sorting. Reason: MVB12A/ESCRT-I supports ubiquitin-dependent endosomal cargo sorting, receptor down-regulation, and multivesicular body pathway transport. Supporting Evidence: file:human/MVB12A/MVB12A-uniprot.txt Required for the sorting of endocytic file:human/MVB12A/MVB12A-uniprot.txt ubiquitinated cargos into multivesicular bodies PMID:18005716 plays essential roles in HIV budding and endosomal protein sorting PMID:16895919 accelerated the EGF receptor's down-regulation PMID:20654576 amounts of EGF receptor bound to ESCRT-I |
| GO:0070062 extracellular exosome | HDA PMID:19056867 Large-scale proteomics and phosphoproteomics of urinary exos... | KEEP AS NON CORE | Summary: extracellular exosome is supported as a localization/context row but is not the core MVB12A function. Reason: The core proteostasis role is ESCRT-I endosomal cargo sorting; this localization is secondary or broad. Supporting Evidence: file:human/MVB12A/MVB12A-uniprot.txt Cytoplasm file:human/MVB12A/MVB12A-uniprot.txt Nucleus file:human/MVB12A/MVB12A-uniprot.txt centrosome PMID:19056867 Large-scale proteomics and phosphoproteomics of urinary exosomes PMID:23533145 In-depth proteomic analyses of exosomes |
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Download this section (compressed HTML)Q: Should MVB12A macroautophagy annotations be retired, modified to ESCRT-I membrane fission, or kept non-core pending MVB12A-specific phagophore-closure perturbation evidence?
Suggested experts: GO autophagy editors, GO ESCRT curators
Q: 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?
Suggested experts: GO molecular function editors, UniProt curators
Experiment: 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.
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.
Type: MVB12A-specific phagophore closure assay
Experiment: 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.
Hypothesis: MVB12A membrane and cargo recognition is better represented by phospholipid binding, ubiquitin binding, and SH3-domain-binding contexts than generic protein binding.
Type: MVB12A molecular-function refinement
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