id: Q9NZ09 gene_symbol: UBAP1 product_type: PROTEIN status: COMPLETE taxon: id: NCBITaxon:9606 label: Homo sapiens description: UBAP1 is an endosome-specific ESCRT-I fourth-subunit variant in TSG101-VPS28-VPS37A-UBAP1 complexes. Its core functions are ubiquitin binding through UBA/SOUBA domains, recognition/sorting of ubiquitinated endosomal cargo into multivesicular bodies, and endosome-specific ESCRT-I complex membership. General ESCRT-I membrane-fission annotations from MVB12A/VPS37B structural work should not be treated as direct UBAP1 evidence. alternative_products: - name: '1' id: Q9NZ09-1 - name: '2' id: Q9NZ09-2 sequence_note: VSP_013650 - name: '3' id: Q9NZ09-3 sequence_note: VSP_046866 - name: '4' id: Q9NZ09-4 sequence_note: VSP_046867 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 a core UBAP1 cellular-component annotation. action: ACCEPT reason: UBAP1 is an endosome-specific ESCRT-I fourth-subunit variant in TSG101-VPS28-VPS37A-UBAP1 complexes. additional_reference_ids: &id001 - PMID:21757351 - PMID:22405001 - file:human/UBAP1/UBAP1-uniprot.txt - file:human/UBAP1/UBAP1-notes.md supported_by: &id002 - &id012 reference_id: file:human/UBAP1/UBAP1-uniprot.txt supporting_text: Component of the ESCRT-I complex - &id013 reference_id: file:human/UBAP1/UBAP1-uniprot.txt supporting_text: consists of TSG101, VPS28, VPS37A and UBAP1 - &id014 reference_id: PMID:21757351 supporting_text: identify a novel ESCRT-I component - &id015 reference_id: PMID:21757351 supporting_text: defines an endosome-specific ESCRT-I complex - &id016 reference_id: PMID:22405001 supporting_text: coassembles in a stable 1:1:1:1 complex - term: id: GO:0043130 label: ubiquitin binding evidence_type: IBA original_reference_id: GO_REF:0000033 qualifier: enables review: summary: Ubiquitin binding is a core UBAP1 molecular-function annotation. action: ACCEPT reason: UBAP1 binds ubiquitinated cargo through UBA/SOUBA domains and supports endosomal ubiquitin homeostasis. additional_reference_ids: &id003 - PMID:21757351 - PMID:22405001 - file:human/UBAP1/UBAP1-uniprot.txt - file:human/UBAP1/UBAP1-notes.md supported_by: &id004 - &id007 reference_id: file:human/UBAP1/UBAP1-uniprot.txt supporting_text: Binds to ubiquitinated cargo proteins - &id008 reference_id: file:human/UBAP1/UBAP1-uniprot.txt supporting_text: Interacts (via UBA domains) with ubiquitinated proteins - &id009 reference_id: PMID:21757351 supporting_text: endosomal ubiquitin homeostasis - &id010 reference_id: PMID:22405001 supporting_text: solenoid of overlapping UBAs - &id011 reference_id: PMID:22405001 supporting_text: interact with ubiquitin - term: id: GO:0043162 label: ubiquitin-dependent protein catabolic process via the multivesicular body sorting pathway evidence_type: IBA original_reference_id: GO_REF:0000033 qualifier: involved_in review: summary: ubiquitin-dependent protein catabolic process via the multivesicular body sorting pathway is supported as a core UBAP1/ESCRT-I endosomal cargo-sorting process. action: ACCEPT reason: UBAP1-containing ESCRT-I is required for sorting ubiquitinated cargo, including EGFR, into the MVB pathway. additional_reference_ids: &id005 - PMID:21757351 - PMID:22405001 - file:human/UBAP1/UBAP1-uniprot.txt - file:human/UBAP1/UBAP1-notes.md supported_by: &id006 - &id021 reference_id: file:human/UBAP1/UBAP1-uniprot.txt supporting_text: sorting of endocytic ubiquitinated cargos - &id022 reference_id: PMID:21757351 supporting_text: required for sorting EGFR to the MVB - &id023 reference_id: PMID:21757351 supporting_text: endosomal ubiquitin homeostasis - &id024 reference_id: PMID:22405001 supporting_text: essential for degradation of antiviral cell-surface proteins - 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 a core UBAP1 cellular-component annotation. action: ACCEPT reason: UBAP1 is an endosome-specific ESCRT-I fourth-subunit variant in TSG101-VPS28-VPS37A-UBAP1 complexes. additional_reference_ids: *id001 supported_by: *id002 - 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 UBAP1/ESCRT-I function. action: ACCEPT reason: UBAP1 is recruited to endosomes as part of an endosome-specific ESCRT-I complex. additional_reference_ids: &id019 - PMID:21757351 - file:human/UBAP1/UBAP1-uniprot.txt - file:human/UBAP1/UBAP1-notes.md supported_by: &id020 - &id025 reference_id: file:human/UBAP1/UBAP1-uniprot.txt supporting_text: Endosome - &id026 reference_id: file:human/UBAP1/UBAP1-uniprot.txt supporting_text: Predominantly cytosolic - &id027 reference_id: file:human/UBAP1/UBAP1-uniprot.txt supporting_text: Recruited to endosomes as part of the ESCRT-I complex - &id028 reference_id: PMID:21757351 supporting_text: endosome-specific ESCRT-I complex - term: id: GO:0005829 label: cytosol evidence_type: IEA original_reference_id: GO_REF:0000044 qualifier: located_in review: summary: cytosol is supported as a localization context but is not the core functional site. action: KEEP_AS_NON_CORE reason: UBAP1 is predominantly cytosolic before recruitment to endosomes; the core proteostasis function occurs in endosomal ESCRT-I cargo sorting. additional_reference_ids: &id017 - PMID:21757351 - file:human/UBAP1/UBAP1-uniprot.txt - file:human/UBAP1/UBAP1-notes.md supported_by: &id018 - reference_id: file:human/UBAP1/UBAP1-uniprot.txt supporting_text: Predominantly cytosolic - reference_id: file:human/UBAP1/UBAP1-uniprot.txt supporting_text: Cytoplasm, cytosol - term: id: GO:0043130 label: ubiquitin binding evidence_type: IEA original_reference_id: GO_REF:0000002 qualifier: enables review: summary: Ubiquitin binding is a core UBAP1 molecular-function annotation. action: ACCEPT reason: UBAP1 binds ubiquitinated cargo through UBA/SOUBA domains and supports endosomal ubiquitin homeostasis. additional_reference_ids: *id003 supported_by: *id004 - term: id: GO:0043162 label: ubiquitin-dependent protein catabolic process via the multivesicular body sorting pathway evidence_type: IEA original_reference_id: GO_REF:0000002 qualifier: involved_in review: summary: ubiquitin-dependent protein catabolic process via the multivesicular body sorting pathway is supported as a core UBAP1/ESCRT-I endosomal cargo-sorting process. action: ACCEPT reason: UBAP1-containing ESCRT-I is required for sorting ubiquitinated cargo, including EGFR, into the MVB pathway. additional_reference_ids: *id005 supported_by: *id006 - 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 UBAP1 function. action: MARK_AS_OVER_ANNOTATED reason: The informative molecular function is ubiquitin binding, and the informative component/process terms are ESCRT-I complex and MVB sorting. proposed_replacement_terms: - id: GO:0043130 label: ubiquitin binding - id: GO:0000813 label: ESCRT I complex additional_reference_ids: - PMID:21757351 - PMID:22405001 - file:human/UBAP1/UBAP1-uniprot.txt - file:human/UBAP1/UBAP1-notes.md - PMID:21757351 - PMID:22405001 - file:human/UBAP1/UBAP1-uniprot.txt - file:human/UBAP1/UBAP1-notes.md supported_by: - *id007 - *id008 - *id009 - *id010 - *id011 - *id012 - *id013 - *id014 - *id015 - *id016 - term: id: GO:0005829 label: cytosol evidence_type: IDA original_reference_id: GO_REF:0000052 qualifier: located_in review: summary: cytosol is supported as a localization context but is not the core functional site. action: KEEP_AS_NON_CORE reason: UBAP1 is predominantly cytosolic before recruitment to endosomes; the core proteostasis function occurs in endosomal ESCRT-I cargo sorting. additional_reference_ids: *id017 supported_by: *id018 - term: id: GO:0000813 label: ESCRT I complex evidence_type: IPI original_reference_id: PMID:21757351 qualifier: part_of review: summary: ESCRT-I complex membership is a core UBAP1 cellular-component annotation. action: ACCEPT reason: UBAP1 is an endosome-specific ESCRT-I fourth-subunit variant in TSG101-VPS28-VPS37A-UBAP1 complexes. additional_reference_ids: *id001 supported_by: *id002 - 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 UBAP1/ESCRT-I function. action: ACCEPT reason: UBAP1 is recruited to endosomes as part of an endosome-specific ESCRT-I complex. additional_reference_ids: *id019 supported_by: *id020 - 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 a core UBAP1/ESCRT-I endosomal cargo-sorting process. action: ACCEPT reason: UBAP1-containing ESCRT-I is required for sorting ubiquitinated cargo, including EGFR, into the MVB pathway. additional_reference_ids: *id005 supported_by: *id006 - 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 a core UBAP1/ESCRT-I endosomal cargo-sorting process. action: ACCEPT reason: UBAP1-containing ESCRT-I is required for sorting ubiquitinated cargo, including EGFR, into the MVB pathway. additional_reference_ids: *id005 supported_by: *id006 - term: id: GO:0090148 label: membrane fission evidence_type: NAS original_reference_id: PMID:32424346 qualifier: involved_in review: summary: Membrane fission is over-transferred for UBAP1 as written. action: MARK_AS_OVER_ANNOTATED reason: The cited structural/autophagy work uses a VPS37B-MVB12A-containing ESCRT-I headpiece and VPS28 mutants, not UBAP1-containing ESCRT-I. proposed_replacement_terms: - id: GO:0000813 label: ESCRT I complex - id: GO:0043162 label: ubiquitin-dependent protein catabolic process via the multivesicular body sorting pathway additional_reference_ids: - PMID:32424346 - file:human/UBAP1/UBAP1-notes.md - PMID:21757351 - PMID:22405001 - file:human/UBAP1/UBAP1-uniprot.txt - file:human/UBAP1/UBAP1-notes.md supported_by: - reference_id: PMID:32424346 supporting_text: comprising TSG101-VPS28-VPS37B-MVB12A - reference_id: PMID:32424346 supporting_text: Mutation of VPS28 helical interface residues - *id007 - *id008 - term: id: GO:0005768 label: endosome evidence_type: EXP original_reference_id: PMID:21757351 qualifier: located_in review: summary: endosome localization is supported and relevant to UBAP1/ESCRT-I function. action: ACCEPT reason: UBAP1 is recruited to endosomes as part of an endosome-specific ESCRT-I complex. additional_reference_ids: *id019 supported_by: *id020 - 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 UBAP1/ESCRT-I function. action: ACCEPT reason: UBAP1 is recruited to endosomes as part of an endosome-specific ESCRT-I complex. additional_reference_ids: *id019 supported_by: *id020 - 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 UBAP1/ESCRT-I function. action: ACCEPT reason: UBAP1 is recruited to endosomes as part of an endosome-specific ESCRT-I complex. additional_reference_ids: *id019 supported_by: *id020 - 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 UBAP1/ESCRT-I function. action: ACCEPT reason: UBAP1 is recruited to endosomes as part of an endosome-specific ESCRT-I complex. additional_reference_ids: *id019 supported_by: *id020 - 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 UBAP1/ESCRT-I function. action: ACCEPT reason: UBAP1 is recruited to endosomes as part of an endosome-specific ESCRT-I complex. additional_reference_ids: *id019 supported_by: *id020 - 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 UBAP1/ESCRT-I function. action: ACCEPT reason: UBAP1 is recruited to endosomes as part of an endosome-specific ESCRT-I complex. additional_reference_ids: *id019 supported_by: *id020 - term: id: GO:0000813 label: ESCRT I complex evidence_type: IDA original_reference_id: PMID:21757351 qualifier: part_of review: summary: ESCRT-I complex membership is a core UBAP1 cellular-component annotation. action: ACCEPT reason: UBAP1 is an endosome-specific ESCRT-I fourth-subunit variant in TSG101-VPS28-VPS37A-UBAP1 complexes. additional_reference_ids: *id001 supported_by: *id002 - term: id: GO:0005829 label: cytosol evidence_type: IDA original_reference_id: PMID:21757351 qualifier: located_in review: summary: cytosol is supported as a localization context but is not the core functional site. action: KEEP_AS_NON_CORE reason: UBAP1 is predominantly cytosolic before recruitment to endosomes; the core proteostasis function occurs in endosomal ESCRT-I cargo sorting. additional_reference_ids: *id017 supported_by: *id018 - term: id: GO:0043130 label: ubiquitin binding evidence_type: IDA original_reference_id: PMID:21757351 qualifier: enables review: summary: Ubiquitin binding is a core UBAP1 molecular-function annotation. action: ACCEPT reason: UBAP1 binds ubiquitinated cargo through UBA/SOUBA domains and supports endosomal ubiquitin homeostasis. additional_reference_ids: *id003 supported_by: *id004 - term: id: GO:0043162 label: ubiquitin-dependent protein catabolic process via the multivesicular body sorting pathway evidence_type: IMP original_reference_id: PMID:21757351 qualifier: involved_in review: summary: ubiquitin-dependent protein catabolic process via the multivesicular body sorting pathway is supported as a core UBAP1/ESCRT-I endosomal cargo-sorting process. action: ACCEPT reason: UBAP1-containing ESCRT-I is required for sorting ubiquitinated cargo, including EGFR, into the MVB pathway. additional_reference_ids: *id005 supported_by: *id006 - term: id: GO:0005737 label: cytoplasm evidence_type: IDA original_reference_id: GO_REF:0000054 qualifier: located_in review: summary: cytoplasm is supported as a localization context but is not the core functional site. action: KEEP_AS_NON_CORE reason: UBAP1 is predominantly cytosolic before recruitment to endosomes; the core proteostasis function occurs in endosomal ESCRT-I cargo sorting. additional_reference_ids: *id017 supported_by: *id018 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:0000052 title: Gene Ontology annotation based on curation of immunofluorescence data findings: [] - id: GO_REF:0000054 title: Gene Ontology annotation based on curation of intracellular localizations of expressed fusion proteins in living cells findings: [] - id: PMID:21757351 title: UBAP1 is a component of an endosome-specific ESCRT-I complex that is essential for MVB sorting. findings: [] - id: PMID:25416956 title: A proteome-scale map of the human interactome network. findings: [] - id: PMID:32424346 title: A helical assembly of human ESCRT-I scaffolds reverse-topology membrane scission. 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:22405001 title: The UBAP1 subunit of ESCRT-I interacts with ubiquitin via a SOUBA domain. findings: [] - id: file:human/UBAP1/UBAP1-uniprot.txt title: UniProtKB record for human UBAP1 findings: [] - id: file:human/UBAP1/UBAP1-notes.md title: UBAP1 review notes findings: [] core_functions: - description: UBAP1 is an endosome-specific ESCRT-I fourth-subunit variant that organizes a TSG101-VPS28-VPS37A-UBAP1 complex for ubiquitinated cargo sorting. molecular_function: id: GO:0043130 label: ubiquitin binding directly_involved_in: - id: GO:0043162 label: ubiquitin-dependent protein catabolic process via the multivesicular body sorting pathway - id: GO:0036258 label: multivesicular body assembly locations: - id: GO:0005768 label: endosome - id: GO:0010008 label: endosome membrane in_complex: id: GO:0000813 label: ESCRT I complex supported_by: - *id012 - *id013 - *id014 - *id015 - *id016 - *id007 - *id008 - *id009 - *id010 - *id011 - *id021 - *id022 - *id023 - *id024 - *id025 - *id026 - *id027 - *id028 proposed_new_terms: [] suggested_questions: - question: Should UBAP1 membrane-fission annotations be removed or kept non-core unless UBAP1-containing ESCRT-I is directly tested in membrane-scission/autophagosome-closure assays? experts: - GO ESCRT curators - GO autophagy editors - question: Should generic UBAP1 protein-binding annotations be replaced by ubiquitin binding and ESCRT-I complex membership? experts: - GO molecular function editors - UniProt curators suggested_experiments: - experiment_type: UBAP1-containing ESCRT-I membrane remodeling assay hypothesis: UBAP1-containing ESCRT-I specializes in endosomal ubiquitinated cargo sorting and should not be assumed to provide the same membrane-fission function as MVB12A-containing ESCRT-I without direct evidence. description: Compare purified or reconstituted UBAP1-ESCRT-I and MVB12A-ESCRT-I complexes in membrane-remodeling assays and in cell-based autophagosome-closure assays. - experiment_type: UBAP1 ubiquitin-binding rescue hypothesis: UBAP1 SOUBA/UBA-mediated ubiquitin binding is required for endosomal cargo sorting. description: Rescue UBAP1 knockout cells with wild-type and SOUBA/UBA mutants and measure EGFR/BST2 cargo degradation, endosomal ubiquitin homeostasis, and ESCRT-I recruitment.