MVB12B 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 MABP acidic-phospholipid binding and ESCRT-I composition evidence. Viral budding and virus maturation reflect pathogen exploitation of ESCRT machinery rather than the main endogenous MVB12B function.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0000813 ESCRT I complex | IBA GO_REF:0000033 | ACCEPT | Summary: ESCRT-I complex membership is the central MVB12B cellular-component annotation. Reason: MVB12B is a metazoan fourth subunit of ESCRT-I supported by direct ESCRT-I composition evidence. Supporting Evidence: file:human/MVB12B/MVB12B-uniprot.txt Component of the ESCRT-I complex file:human/MVB12B/MVB12B-uniprot.txt which consists of TSG101, VPS28, a VPS37 file:human/MVB12B/MVB12B-uniprot.txt Interacts with TSG101 file:human/MVB12B/MVB12B-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:20654576 MVB12A and MVB12B are subunits of ESCRT-I file:human/MVB12B/MVB12B-deep-research-falcon.md structural component of the ESCRT-I |
| GO:0005770 late endosome | IBA GO_REF:0000033 | ACCEPT | Summary: late endosome localization is supported and relevant to MVB12B/ESCRT-I function. Reason: MVB12B is an ESCRT-I subunit associated with endosomes/late-endosome membrane and endosomal cargo sorting. Supporting Evidence: file:human/MVB12B/MVB12B-uniprot.txt Endosome file:human/MVB12B/MVB12B-uniprot.txt Late endosome membrane PMID:22232651 function both in protein transport at endosomes |
| 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. Reason: MVB12B/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 |
| GO:0042058 regulation of epidermal growth factor receptor signaling pathway | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: EGF/EGFR pathway context is supported but secondary for MVB12B. Reason: PMID:20654576 links MVB12B post-translational regulation to EGF stimulation and ESCRT-I function, but EGFR regulation is a substrate/context-specific consequence rather than the core function. Supporting Evidence: PMID:20654576 increased upon EGF stimulation PMID:20654576 led to the instability and inclusion of MVB12B |
| 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: MVB12B/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 |
| GO:0005737 cytoplasm | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: cytoplasm is supported as a localization/context row but is not the core MVB12B function. Reason: The core proteostasis role is ESCRT-I endosomal cargo sorting; this localization is secondary or broad. Supporting Evidence: file:human/MVB12B/MVB12B-uniprot.txt Cytoplasm file:human/MVB12B/MVB12B-uniprot.txt Nucleus file:human/MVB12B/MVB12B-uniprot.txt plasma membrane PMID:22232651 autonomously localizing to subcellular puncta and to the plasma membrane PMID:19056867 Large-scale proteomics and phosphoproteomics of urinary exosomes |
| GO:0005768 endosome | IEA GO_REF:0000044 | ACCEPT | Summary: endosome localization is supported and relevant to MVB12B/ESCRT-I function. Reason: MVB12B is an ESCRT-I subunit associated with endosomes/late-endosome membrane and endosomal cargo sorting. Supporting Evidence: file:human/MVB12B/MVB12B-uniprot.txt Endosome file:human/MVB12B/MVB12B-uniprot.txt Late endosome membrane PMID:22232651 function both in protein transport at endosomes |
| GO:0031902 late endosome membrane | IEA GO_REF:0000044 | ACCEPT | Summary: late endosome membrane localization is supported and relevant to MVB12B/ESCRT-I function. Reason: MVB12B is an ESCRT-I subunit associated with endosomes/late-endosome membrane and endosomal cargo sorting. Supporting Evidence: file:human/MVB12B/MVB12B-uniprot.txt Endosome file:human/MVB12B/MVB12B-uniprot.txt Late endosome membrane PMID:22232651 function both in protein transport at endosomes |
| GO:0005515 protein binding | IPI PMID:25416956 A proteome-scale map of the human interactome network. | MARK AS OVER ANNOTATED | Summary: Protein binding is too generic to represent MVB12B function. Reason: The informative annotations are ESCRT-I complex membership and phospholipid-binding/endosomal sorting context, not generic protein binding from broad interaction screens. Proposed replacements: ESCRT I complex Supporting Evidence: file:human/MVB12B/MVB12B-notes.md broad localization/context rows but are not the core proteostasis function |
| 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 MVB12B function. Reason: The informative annotations are ESCRT-I complex membership and phospholipid-binding/endosomal sorting context, not generic protein binding from broad interaction screens. Proposed replacements: ESCRT I complex Supporting Evidence: file:human/MVB12B/MVB12B-notes.md broad localization/context rows but are not the core proteostasis function |
| 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 MVB12B function. Reason: The informative annotations are ESCRT-I complex membership and phospholipid-binding/endosomal sorting context, not generic protein binding from broad interaction screens. Proposed replacements: ESCRT I complex Supporting Evidence: file:human/MVB12B/MVB12B-notes.md broad localization/context rows but are not the core proteostasis function |
| 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: MVB12B/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 |
| GO:0010008 endosome membrane | TAS Reactome:R-HSA-184269 | ACCEPT | Summary: endosome membrane localization is supported and relevant to MVB12B/ESCRT-I function. Reason: MVB12B is an ESCRT-I subunit associated with endosomes/late-endosome membrane and endosomal cargo sorting. Supporting Evidence: file:human/MVB12B/MVB12B-uniprot.txt Endosome file:human/MVB12B/MVB12B-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 MVB12B/ESCRT-I function. Reason: MVB12B is an ESCRT-I subunit associated with endosomes/late-endosome membrane and endosomal cargo sorting. Supporting Evidence: file:human/MVB12B/MVB12B-uniprot.txt Endosome file:human/MVB12B/MVB12B-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 MVB12B/ESCRT-I function. Reason: MVB12B is an ESCRT-I subunit associated with endosomes/late-endosome membrane and endosomal cargo sorting. Supporting Evidence: file:human/MVB12B/MVB12B-uniprot.txt Endosome file:human/MVB12B/MVB12B-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 MVB12B/ESCRT-I function. Reason: MVB12B is an ESCRT-I subunit associated with endosomes/late-endosome membrane and endosomal cargo sorting. Supporting Evidence: file:human/MVB12B/MVB12B-uniprot.txt Endosome file:human/MVB12B/MVB12B-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 MVB12B/ESCRT-I function. Reason: MVB12B is an ESCRT-I subunit associated with endosomes/late-endosome membrane and endosomal cargo sorting. Supporting Evidence: file:human/MVB12B/MVB12B-uniprot.txt Endosome file:human/MVB12B/MVB12B-uniprot.txt Late endosome membrane PMID:22232651 function both in protein transport at endosomes |
| 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: MVB12B/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 |
| 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 MVB12B cellular-component annotation. Reason: MVB12B is a metazoan fourth subunit of ESCRT-I supported by direct ESCRT-I composition evidence. Supporting Evidence: file:human/MVB12B/MVB12B-uniprot.txt Component of the ESCRT-I complex file:human/MVB12B/MVB12B-uniprot.txt which consists of TSG101, VPS28, a VPS37 file:human/MVB12B/MVB12B-uniprot.txt Interacts with TSG101 file:human/MVB12B/MVB12B-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:20654576 MVB12A and MVB12B are subunits of ESCRT-I file:human/MVB12B/MVB12B-deep-research-falcon.md structural component of the ESCRT-I |
| 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 MVB12B cellular-component annotation. Reason: MVB12B is a metazoan fourth subunit of ESCRT-I supported by direct ESCRT-I composition evidence. Supporting Evidence: file:human/MVB12B/MVB12B-uniprot.txt Component of the ESCRT-I complex file:human/MVB12B/MVB12B-uniprot.txt which consists of TSG101, VPS28, a VPS37 file:human/MVB12B/MVB12B-uniprot.txt Interacts with TSG101 file:human/MVB12B/MVB12B-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:20654576 MVB12A and MVB12B are subunits of ESCRT-I file:human/MVB12B/MVB12B-deep-research-falcon.md structural component of the ESCRT-I |
| 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 ESCRT-I complex membership. Reason: The cited MVB12A/B paper supports ESCRT-I subunit/complex membership rather than a standalone generic protein-binding function. Proposed replacements: ESCRT I complex Supporting Evidence: file:human/MVB12B/MVB12B-uniprot.txt Component of the ESCRT-I complex file:human/MVB12B/MVB12B-uniprot.txt which consists of TSG101, VPS28, a VPS37 file:human/MVB12B/MVB12B-uniprot.txt Interacts with TSG101 file:human/MVB12B/MVB12B-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:20654576 MVB12A and MVB12B are subunits of ESCRT-I file:human/MVB12B/MVB12B-deep-research-falcon.md structural component of the ESCRT-I |
| GO:0005634 nucleus | IDA PMID:22232651 Structural basis for membrane targeting by the MVB12-associa... | KEEP AS NON CORE | Summary: nucleus is supported as a localization/context row but is not the core MVB12B function. Reason: The core proteostasis role is ESCRT-I endosomal cargo sorting; this localization is secondary or broad. Supporting Evidence: file:human/MVB12B/MVB12B-uniprot.txt Cytoplasm file:human/MVB12B/MVB12B-uniprot.txt Nucleus file:human/MVB12B/MVB12B-uniprot.txt plasma membrane PMID:22232651 autonomously localizing to subcellular puncta and to the plasma membrane PMID:19056867 Large-scale proteomics and phosphoproteomics of urinary exosomes |
| GO:0005769 early endosome | IDA PMID:22232651 Structural basis for membrane targeting by the MVB12-associa... | ACCEPT | Summary: early endosome localization is supported and relevant to MVB12B/ESCRT-I function. Reason: MVB12B is an ESCRT-I subunit associated with endosomes/late-endosome membrane and endosomal cargo sorting. Supporting Evidence: file:human/MVB12B/MVB12B-uniprot.txt Endosome file:human/MVB12B/MVB12B-uniprot.txt Late endosome membrane PMID:22232651 function both in protein transport at endosomes |
| GO:0005770 late endosome | IDA PMID:22232651 Structural basis for membrane targeting by the MVB12-associa... | ACCEPT | Summary: late endosome localization is supported and relevant to MVB12B/ESCRT-I function. Reason: MVB12B is an ESCRT-I subunit associated with endosomes/late-endosome membrane and endosomal cargo sorting. Supporting Evidence: file:human/MVB12B/MVB12B-uniprot.txt Endosome file:human/MVB12B/MVB12B-uniprot.txt Late endosome membrane PMID:22232651 function both in protein transport at endosomes |
| GO:0005829 cytosol | IDA PMID:22232651 Structural basis for membrane targeting by the MVB12-associa... | KEEP AS NON CORE | Summary: cytosol is supported as a localization/context row but is not the core MVB12B function. Reason: The core proteostasis role is ESCRT-I endosomal cargo sorting; this localization is secondary or broad. Supporting Evidence: file:human/MVB12B/MVB12B-uniprot.txt Cytoplasm file:human/MVB12B/MVB12B-uniprot.txt Nucleus file:human/MVB12B/MVB12B-uniprot.txt plasma membrane PMID:22232651 autonomously localizing to subcellular puncta and to the plasma membrane PMID:19056867 Large-scale proteomics and phosphoproteomics of urinary exosomes |
| GO:0005886 plasma membrane | IDA PMID:22232651 Structural basis for membrane targeting by the MVB12-associa... | KEEP AS NON CORE | Summary: plasma membrane is supported as a localization/context row but is not the core MVB12B function. Reason: The core proteostasis role is ESCRT-I endosomal cargo sorting; this localization is secondary or broad. Supporting Evidence: file:human/MVB12B/MVB12B-uniprot.txt Cytoplasm file:human/MVB12B/MVB12B-uniprot.txt Nucleus file:human/MVB12B/MVB12B-uniprot.txt plasma membrane PMID:22232651 autonomously localizing to subcellular puncta and to the plasma membrane PMID:19056867 Large-scale proteomics and phosphoproteomics of urinary 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 |
| 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 MVB12B function. Reason: The core proteostasis role is ESCRT-I endosomal cargo sorting; this localization is secondary or broad. Supporting Evidence: file:human/MVB12B/MVB12B-uniprot.txt Cytoplasm file:human/MVB12B/MVB12B-uniprot.txt Nucleus file:human/MVB12B/MVB12B-uniprot.txt plasma membrane PMID:22232651 autonomously localizing to subcellular puncta and to the plasma membrane PMID:19056867 Large-scale proteomics and phosphoproteomics of urinary 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: EGF/EGFR pathway context is supported but secondary for MVB12B. Reason: PMID:20654576 links MVB12B post-translational regulation to EGF stimulation and ESCRT-I function, but EGFR regulation is a substrate/context-specific consequence rather than the core function. Supporting Evidence: PMID:20654576 increased upon EGF stimulation PMID:20654576 led to the instability and inclusion of MVB12B |
| GO:0043130 ubiquitin binding | IDA NOT PMID:20654576 Distinct functions of human MVB12A and MVB12B in the ESCRT-I... | ACCEPT | Summary: MVB12B does NOT bind ubiquitin; this is an experimentally-supported negated (NOT) annotation. Reason: This is a curator-made experimental NOT|enables IDA (negated=true) from PMID:20654576, i.e. the curator established that MVB12B does not directly bind ubiquitin (in ESCRT-I, the TSG101 UEV domain provides ubiquitin binding). The negation is the finding and should be accepted, deferring to the curator's full-text reading rather than left undecided; the cached abstract foregrounds MVB12B ubiquitination, which is a different assay. Supporting Evidence: PMID:20654576 ubiquitination of Lys264 and Lys290 of MVB12B file:human/MVB12B/MVB12B-notes.md The negated ubiquitin-binding row is therefore ACCEPTed as the experimentally-supported non-binding finding |
| 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 MVB12B/ESCRT-I endosomal cargo sorting. Reason: MVB12B/ESCRT-I supports ubiquitin-dependent endosomal cargo sorting into multivesicular bodies. Supporting Evidence: file:human/MVB12B/MVB12B-uniprot.txt Required for the sorting of endocytic file:human/MVB12B/MVB12B-uniprot.txt ubiquitinated cargos into multivesicular bodies PMID:18005716 plays essential roles in HIV budding and endosomal protein sorting PMID:20654576 sorting of ubiquitinated cargo protein from the plasma membrane to the endosomal vesicle file:human/MVB12B/MVB12B-deep-research-falcon.md MVB12B fulfills an adaptor/scaffold role in recognizing and sorting ubiquitinated membrane proteins into intraluminal vesicles |
| 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 MVB12B function. Reason: The core proteostasis role is ESCRT-I endosomal cargo sorting; this localization is secondary or broad. Supporting Evidence: file:human/MVB12B/MVB12B-uniprot.txt Cytoplasm file:human/MVB12B/MVB12B-uniprot.txt Nucleus file:human/MVB12B/MVB12B-uniprot.txt plasma membrane PMID:22232651 autonomously localizing to subcellular puncta and to the plasma membrane PMID:19056867 Large-scale proteomics and phosphoproteomics of urinary exosomes |
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Download this section (compressed HTML)Q: Should MVB12B ubiquitin binding be accepted only after full-text confirmation of PMID:20654576, or should this row be removed as a conflation with MVB12B ubiquitination?
Suggested experts: GO molecular function editors, UniProt curators
Q: Should MVB12B generic protein-binding annotations be replaced by ESCRT-I complex membership and phospholipid binding where the evidence supports those more specific terms?
Suggested experts: GO molecular function editors, GO ESCRT curators
Q: Does the TBK1/STING-dependent phosphorylation of MVB12B (reportedly at S222) that drives sorting of cytosolic DNA into extracellular vesicles for paracrine cGAS-STING signaling (Nandakumar 2019, Kuchitsu 2023, summarized in the falcon deep-research report) warrant an MVB12B-specific innate-immune / extracellular-vesicle cargo-loading annotation, once the primary full text is verified? This MVB12B-specific axis is not currently captured in the GOA rows.
Suggested experts: GO biological process editors, GO immunology curators
Experiment: Test purified MVB12B MABP/UMA regions for acidic phospholipid binding and ubiquitin binding using matched mutants, then measure rescue in endosomal cargo-sorting assays.
Hypothesis: MVB12B membrane recognition is better represented by phospholipid binding than generic protein binding, while ubiquitin binding requires direct confirmation.
Type: MVB12B molecular-function refinement
Experiment: Compare MVB12A and MVB12B knockout/rescue in EGFR degradation, ESCRT-I recruitment, and HIV budding assays under matched expression conditions.
Hypothesis: MVB12A and MVB12B differ in endosomal cargo-sorting and EGF-stimulated post-translational regulation.
Type: MVB12 paralog ESCRT-I sorting comparison
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