id: Q9H7P6 gene_symbol: MVB12B product_type: PROTEIN status: COMPLETE taxon: id: NCBITaxon:9606 label: Homo sapiens description: >- 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. alternative_products: - name: '1' id: Q9H7P6-1 - name: '2' id: Q9H7P6-2 sequence_note: VSP_020364 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 MVB12B cellular-component annotation. action: ACCEPT reason: MVB12B is a metazoan fourth subunit of ESCRT-I supported by direct ESCRT-I composition evidence. additional_reference_ids: &id007 - PMID:18005716 - PMID:20654576 - file:human/MVB12B/MVB12B-uniprot.txt - file:human/MVB12B/MVB12B-notes.md - file:human/MVB12B/MVB12B-deep-research-falcon.md supported_by: &id008 - &id013 reference_id: file:human/MVB12B/MVB12B-uniprot.txt supporting_text: Component of the ESCRT-I complex - &id014 reference_id: file:human/MVB12B/MVB12B-uniprot.txt supporting_text: which consists of TSG101, VPS28, a VPS37 - &id015 reference_id: file:human/MVB12B/MVB12B-uniprot.txt supporting_text: Interacts with TSG101 - &id016 reference_id: file:human/MVB12B/MVB12B-uniprot.txt supporting_text: Interacts with VPS28 - &id017 reference_id: PMID:18005716 supporting_text: constitute the fourth class of metazoan ESCRT-I subunits - &id018 reference_id: PMID:18005716 supporting_text: one copy of each of the four subunit types - &id019 reference_id: PMID:18005716 supporting_text: associate with the core region of the binary TSG101-VPS37 complex - &id020 reference_id: PMID:20654576 supporting_text: MVB12A and MVB12B are subunits of ESCRT-I - reference_id: file:human/MVB12B/MVB12B-deep-research-falcon.md supporting_text: structural component of the ESCRT-I - term: id: GO:0005770 label: late endosome evidence_type: IBA original_reference_id: GO_REF:0000033 qualifier: is_active_in review: summary: late endosome localization is supported and relevant to MVB12B/ESCRT-I function. action: ACCEPT reason: MVB12B is an ESCRT-I subunit associated with endosomes/late-endosome membrane and endosomal cargo sorting. additional_reference_ids: &id003 - PMID:22232651 - file:human/MVB12B/MVB12B-uniprot.txt - file:human/MVB12B/MVB12B-notes.md supported_by: &id004 - &id025 reference_id: file:human/MVB12B/MVB12B-uniprot.txt supporting_text: Endosome - &id026 reference_id: file:human/MVB12B/MVB12B-uniprot.txt supporting_text: Late endosome membrane - &id027 reference_id: PMID:22232651 supporting_text: function both in protein transport at endosomes - 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. action: KEEP_AS_NON_CORE reason: MVB12B/MVB12 subunits regulate HIV/viral budding and maturation, but the core cellular proteostasis role is endosomal ESCRT-I cargo sorting. additional_reference_ids: &id001 - PMID:18005716 - file:human/MVB12B/MVB12B-notes.md supported_by: &id002 - 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 - 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: EGF/EGFR pathway context is supported but secondary for MVB12B. action: KEEP_AS_NON_CORE 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. additional_reference_ids: &id011 - PMID:20654576 - file:human/MVB12B/MVB12B-notes.md supported_by: &id012 - reference_id: PMID:20654576 supporting_text: increased upon EGF stimulation - reference_id: PMID:20654576 supporting_text: led to the instability and inclusion of MVB12B - 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: MVB12B/MVB12 subunits regulate HIV/viral budding and maturation, but the core cellular proteostasis role is endosomal ESCRT-I cargo sorting. additional_reference_ids: *id001 supported_by: *id002 - term: id: GO:0005737 label: cytoplasm evidence_type: IEA original_reference_id: GO_REF:0000117 qualifier: located_in review: summary: cytoplasm is supported as a localization/context row but is not the core MVB12B 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: &id009 - PMID:19056867 - PMID:22232651 - file:human/MVB12B/MVB12B-uniprot.txt - file:human/MVB12B/MVB12B-notes.md supported_by: &id010 - reference_id: file:human/MVB12B/MVB12B-uniprot.txt supporting_text: Cytoplasm - reference_id: file:human/MVB12B/MVB12B-uniprot.txt supporting_text: Nucleus - reference_id: file:human/MVB12B/MVB12B-uniprot.txt supporting_text: plasma membrane - reference_id: PMID:22232651 supporting_text: autonomously localizing to subcellular puncta and to the plasma membrane - reference_id: PMID:19056867 supporting_text: Large-scale proteomics and phosphoproteomics of urinary exosomes - 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 MVB12B/ESCRT-I function. action: ACCEPT reason: MVB12B is an ESCRT-I subunit associated with endosomes/late-endosome membrane and endosomal cargo sorting. additional_reference_ids: *id003 supported_by: *id004 - 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 MVB12B/ESCRT-I function. action: ACCEPT reason: MVB12B is an ESCRT-I subunit associated with endosomes/late-endosome membrane and endosomal cargo sorting. additional_reference_ids: *id003 supported_by: *id004 - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:25416956 qualifier: enables review: summary: Protein binding is too generic to represent MVB12B function. action: MARK_AS_OVER_ANNOTATED reason: The informative annotations are ESCRT-I complex membership and phospholipid-binding/endosomal sorting context, not generic protein binding from broad interaction screens. proposed_replacement_terms: - id: GO:0000813 label: ESCRT I complex additional_reference_ids: &id005 - PMID:25416956 - PMID:28514442 - PMID:33961781 - file:human/MVB12B/MVB12B-notes.md supported_by: &id006 - reference_id: file:human/MVB12B/MVB12B-notes.md supporting_text: broad localization/context rows but are not the core proteostasis function - 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 MVB12B function. action: MARK_AS_OVER_ANNOTATED reason: The informative annotations are ESCRT-I complex membership and phospholipid-binding/endosomal sorting context, not generic protein binding from broad interaction screens. proposed_replacement_terms: - id: GO:0000813 label: ESCRT I complex additional_reference_ids: *id005 supported_by: *id006 - 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 MVB12B function. action: MARK_AS_OVER_ANNOTATED reason: The informative annotations are ESCRT-I complex membership and phospholipid-binding/endosomal sorting context, not generic protein binding from broad interaction screens. 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: MVB12B/MVB12 subunits regulate HIV/viral budding and maturation, but the core cellular proteostasis role is endosomal ESCRT-I cargo sorting. additional_reference_ids: *id001 supported_by: *id002 - term: id: GO:0010008 label: endosome membrane evidence_type: TAS original_reference_id: Reactome:R-HSA-184269 qualifier: located_in review: summary: endosome membrane localization is supported and relevant to MVB12B/ESCRT-I function. action: ACCEPT reason: MVB12B is an ESCRT-I subunit associated with endosomes/late-endosome membrane and endosomal 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-3149434 qualifier: located_in review: summary: endosome membrane localization is supported and relevant to MVB12B/ESCRT-I function. action: ACCEPT reason: MVB12B is an ESCRT-I subunit associated with endosomes/late-endosome membrane and endosomal 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-3159232 qualifier: located_in review: summary: endosome membrane localization is supported and relevant to MVB12B/ESCRT-I function. action: ACCEPT reason: MVB12B is an ESCRT-I subunit associated with endosomes/late-endosome membrane and endosomal 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-917696 qualifier: located_in review: summary: endosome membrane localization is supported and relevant to MVB12B/ESCRT-I function. action: ACCEPT reason: MVB12B is an ESCRT-I subunit associated with endosomes/late-endosome membrane and endosomal 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-917730 qualifier: located_in review: summary: endosome membrane localization is supported and relevant to MVB12B/ESCRT-I function. action: ACCEPT reason: MVB12B is an ESCRT-I subunit associated with endosomes/late-endosome membrane and endosomal 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: MVB12B/MVB12 subunits regulate HIV/viral budding and maturation, but the core cellular proteostasis role is endosomal ESCRT-I cargo sorting. additional_reference_ids: *id001 supported_by: *id002 - 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 MVB12B cellular-component annotation. action: ACCEPT reason: MVB12B is a metazoan fourth subunit of ESCRT-I supported by direct ESCRT-I composition evidence. 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 MVB12B cellular-component annotation. action: ACCEPT reason: MVB12B is a metazoan fourth subunit of ESCRT-I supported by direct ESCRT-I composition evidence. additional_reference_ids: *id007 supported_by: *id008 - 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 ESCRT-I complex membership. action: MODIFY reason: The cited MVB12A/B paper supports ESCRT-I subunit/complex membership rather than a standalone generic protein-binding function. proposed_replacement_terms: - id: GO:0000813 label: ESCRT I complex additional_reference_ids: *id007 supported_by: *id008 - term: id: GO:0005634 label: nucleus evidence_type: IDA original_reference_id: PMID:22232651 qualifier: located_in review: summary: nucleus is supported as a localization/context row but is not the core MVB12B 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: *id009 supported_by: *id010 - term: id: GO:0005769 label: early endosome evidence_type: IDA original_reference_id: PMID:22232651 qualifier: located_in review: summary: early endosome localization is supported and relevant to MVB12B/ESCRT-I function. action: ACCEPT reason: MVB12B is an ESCRT-I subunit associated with endosomes/late-endosome membrane and endosomal cargo sorting. additional_reference_ids: *id003 supported_by: *id004 - term: id: GO:0005770 label: late endosome evidence_type: IDA original_reference_id: PMID:22232651 qualifier: located_in review: summary: late endosome localization is supported and relevant to MVB12B/ESCRT-I function. action: ACCEPT reason: MVB12B is an ESCRT-I subunit associated with endosomes/late-endosome membrane and endosomal cargo sorting. additional_reference_ids: *id003 supported_by: *id004 - term: id: GO:0005829 label: cytosol evidence_type: IDA original_reference_id: PMID:22232651 qualifier: located_in review: summary: cytosol is supported as a localization/context row but is not the core MVB12B 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: *id009 supported_by: *id010 - term: id: GO:0005886 label: plasma membrane evidence_type: IDA original_reference_id: PMID:22232651 qualifier: located_in review: summary: plasma membrane is supported as a localization/context row but is not the core MVB12B 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: *id009 supported_by: *id010 - 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/MVB12B/MVB12B-notes.md supported_by: - &id028 reference_id: PMID:22232651 supporting_text: MABP domains of the MVB12A and B subunits - &id029 reference_id: PMID:22232651 supporting_text: bind in vitro to liposomes containing acidic lipids - &id030 reference_id: PMID:22232651 supporting_text: coincidence detector for acidic phospholipids and protein ligands - 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 MVB12B 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: *id009 supported_by: *id010 - 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: EGF/EGFR pathway context is supported but secondary for MVB12B. action: KEEP_AS_NON_CORE 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. additional_reference_ids: *id011 supported_by: *id012 - term: id: GO:0043130 label: ubiquitin binding evidence_type: IDA original_reference_id: PMID:20654576 qualifier: enables negated: true review: summary: MVB12B does NOT bind ubiquitin; this is an experimentally-supported negated (NOT) annotation. action: ACCEPT 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. additional_reference_ids: - PMID:20654576 - file:human/MVB12B/MVB12B-notes.md supported_by: - reference_id: PMID:20654576 supporting_text: ubiquitination of Lys264 and Lys290 of MVB12B - reference_id: file:human/MVB12B/MVB12B-notes.md supporting_text: The negated ubiquitin-binding row is therefore ACCEPTed as the experimentally-supported non-binding finding - 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 MVB12B/ESCRT-I endosomal cargo sorting. action: ACCEPT reason: MVB12B/ESCRT-I supports ubiquitin-dependent endosomal cargo sorting into multivesicular bodies. additional_reference_ids: - PMID:18005716 - PMID:20654576 - file:human/MVB12B/MVB12B-uniprot.txt - file:human/MVB12B/MVB12B-notes.md - file:human/MVB12B/MVB12B-deep-research-falcon.md supported_by: - &id021 reference_id: file:human/MVB12B/MVB12B-uniprot.txt supporting_text: Required for the sorting of endocytic - &id022 reference_id: file:human/MVB12B/MVB12B-uniprot.txt supporting_text: ubiquitinated cargos into multivesicular bodies - &id023 reference_id: PMID:18005716 supporting_text: plays essential roles in HIV budding and endosomal protein sorting - &id024 reference_id: PMID:20654576 supporting_text: sorting of ubiquitinated cargo protein from the plasma membrane to the endosomal vesicle - reference_id: file:human/MVB12B/MVB12B-deep-research-falcon.md supporting_text: MVB12B fulfills an adaptor/scaffold role in recognizing and sorting ubiquitinated membrane proteins into intraluminal vesicles - 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 MVB12B 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: *id009 supported_by: *id010 references: - id: GO_REF:0000033 title: Annotation inferences using phylogenetic trees findings: [] - id: GO_REF:0000044 title: Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular Location vocabulary mapping, accompanied by conservative changes to GO terms applied by UniProt findings: [] - id: GO_REF:0000117 title: Electronic Gene Ontology annotations created by ARBA machine learning models findings: [] - id: PMID:18005716 title: Identification of human MVB12 proteins as ESCRT-I subunits that function in HIV budding. findings: [] - id: PMID:19056867 title: Large-scale proteomics and phosphoproteomics of urinary exosomes. 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:25416956 title: A proteome-scale map of the human interactome network. findings: [] - id: PMID:28514442 title: Architecture of the human interactome defines protein communities and disease networks. 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: file:human/MVB12B/MVB12B-uniprot.txt title: UniProtKB record for human MVB12B findings: [] - id: file:human/MVB12B/MVB12B-notes.md title: MVB12B review notes findings: [] - id: file:human/MVB12B/MVB12B-deep-research-falcon.md title: Falcon deep research report for MVB12B findings: [] reference_review: relevance: HIGH correctness: UNVERIFIED review_notes: >- LLM-synthesized deep-research report (Edison/Falcon); not independently verified against primary full text, so marked UNVERIFIED. MVB12B-SPECIFIC and well-anchored: (1) MVB12B is a fourth-subunit ESCRT-I member that acts as a structural/adaptor subunit in sorting ubiquitinated cargo into MVBs, and (2) the TBK1/STING-dependent phosphorylation of MVB12B (S222) that drives sorting of DNA into extracellular vesicles for paracrine cGAS-STING signaling (Nandakumar 2019; Kuchitsu 2023) -- this immune/EV-sorting axis is a genuine MVB12B-specific function not currently captured in the GOA rows. CAUTION: many statements about cytokinesis/abscission, autophagosome closure, membrane repair, and broad enveloped-virus egress are explicitly flagged in the report as ESCRT-I holo-complex level (or MVB12A-paralog structural inference, e.g. the human ESCRT-I head structure was solved with MVB12A not MVB12B) rather than MVB12B-specific, and should not be attributed to the MVB12B subunit. Used here only to corroborate the MVB12B adaptor/cargo-sorting and ESCRT-I-membership annotations, not to add holo-complex processes. core_functions: - description: MVB12B is a fourth subunit of metazoan ESCRT-I complexes and helps organize MVB12B-containing TSG101-VPS28-VPS37 assemblies for endosomal cargo sorting. directly_involved_in: - id: GO:0043162 label: ubiquitin-dependent protein catabolic process via the multivesicular body sorting pathway locations: - id: GO:0005768 label: endosome - id: GO:0010008 label: endosome membrane - id: GO:0031902 label: late endosome membrane in_complex: id: GO:0000813 label: ESCRT I complex supported_by: - *id013 - *id014 - *id015 - *id016 - *id017 - *id018 - *id019 - *id020 - *id021 - *id022 - *id023 - *id024 - *id025 - *id026 - *id027 - description: MVB12B MABP-domain acidic phospholipid binding supports ESCRT-I membrane targeting context. molecular_function: id: GO:0005543 label: phospholipid binding directly_involved_in: - id: GO:0043162 label: ubiquitin-dependent protein catabolic process via the multivesicular body sorting pathway locations: - id: GO:0005769 label: early endosome - id: GO:0005770 label: late endosome in_complex: id: GO:0000813 label: ESCRT I complex supported_by: - *id028 - *id029 - *id030 - *id013 - *id014 - *id015 - *id016 - *id017 - *id018 - *id019 - *id020 proposed_new_terms: [] suggested_questions: - question: 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? experts: - GO molecular function editors - UniProt curators - question: Should MVB12B generic protein-binding annotations be replaced by ESCRT-I complex membership and phospholipid binding where the evidence supports those more specific terms? experts: - GO molecular function editors - GO ESCRT curators - question: 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. experts: - GO biological process editors - GO immunology curators suggested_experiments: - experiment_type: MVB12B molecular-function refinement hypothesis: MVB12B membrane recognition is better represented by phospholipid binding than generic protein binding, while ubiquitin binding requires direct confirmation. description: Test purified MVB12B MABP/UMA regions for acidic phospholipid binding and ubiquitin binding using matched mutants, then measure rescue in endosomal cargo-sorting assays. - experiment_type: MVB12 paralog ESCRT-I sorting comparison hypothesis: MVB12A and MVB12B differ in endosomal cargo-sorting and EGF-stimulated post-translational regulation. description: Compare MVB12A and MVB12B knockout/rescue in EGFR degradation, ESCRT-I recruitment, and HIV budding assays under matched expression conditions.