VPS28 is a conserved core subunit of human ESCRT-I. It pairs with TSG101, a VPS37 paralog, and an MVB12/UBAP-family subunit to organize ESCRT-I for ubiquitin-dependent endosomal cargo sorting, multivesicular body assembly, reverse-topology membrane remodeling, and phagophore/autophagosome closure. Unlike TSG101, VPS28 is not well supported as a direct ubiquitin-binding protein; its core role is ESCRT-I structural/scaffold assembly and membrane-site recruitment.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0005829 cytosol | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: cytosol localization is supported but broad and non-core. Reason: VPS28 is predominantly cytosolic as a soluble ESCRT-I component before membrane recruitment, but the core proteostasis function is ESCRT-I activity at endosomal/phagophore membranes. Supporting Evidence: PMID:11134028 cytosolic protein that interacts with TSG101/mammalian VPS23 PMID:11134028 TSG101 and hVPS28 are predominantly cytosolic |
| GO:0043130 ubiquitin binding | IBA GO_REF:0000033 | MARK AS OVER ANNOTATED | Summary: Direct ubiquitin binding is over-annotated for VPS28. Reason: The cited paper shows the TSG101-hVPS28 complex binds ubiquitin, but isolated hVPS28 does not; the binding is attributed to TSG101 UEV-domain recognition, so VPS28 should not be curated as directly enabling ubiquitin binding. Proposed replacements: ESCRT I complex ubiquitin-dependent protein catabolic process via the multivesicular body sorting pathway Supporting Evidence: PMID:11916981 Both TSG101 and hVPS28 bound specifically to ubiquitin-agarose PMID:11916981 hVPS28 did not bind to ubiquitin-agarose PMID:11916981 complex binding to ubiquitin via the Ubc domain of TSG101 |
| GO:0000813 ESCRT I complex | IBA GO_REF:0000033 | ACCEPT | Summary: ESCRT-I complex membership is the central VPS28 cellular-component annotation. Reason: VPS28 is a constitutive ESCRT-I subunit in TSG101-VPS28-VPS37-MVB12/UBAP variant complexes. Supporting Evidence: file:human/VPS28/VPS28-uniprot.txt Component of the ESCRT-I complex file:human/VPS28/VPS28-uniprot.txt which consists of TSG101, VPS28, a VPS37 PMID:18005716 All ESCRT-I complexes contain three PMID:18005716 TSG101, VPS28, and VPS37 PMID:20654576 comprises a heterotetramer of TSG101 |
| GO:0043328 protein transport to vacuole involved in ubiquitin-dependent protein catabolic process via the multivesicular body sorting pathway | IBA GO_REF:0000033 | ACCEPT | Summary: protein transport to vacuole involved in ubiquitin-dependent protein catabolic process via the multivesicular body sorting pathway is supported as part of the core ESCRT-I endosomal cargo-sorting role. Reason: VPS28/ESCRT-I supports ubiquitin-dependent endosomal receptor/cargo sorting into MVBs and delivery toward lysosomal degradation. Supporting Evidence: PMID:11134028 directly involved in endosomal sorting PMID:11916981 TSG101 and VPS28 are localized to ubiquitin-rich endosomes PMID:11916981 antibodies to VPS28 specifically impair EGF degradation PMID:21757351 required for sorting EGFR to the MVB file:human/VPS28/VPS28-uniprot.txt Component of the ESCRT-I complex, a regulator of vesicular |
| GO:0000813 ESCRT I complex | IEA GO_REF:0000120 | ACCEPT | Summary: ESCRT-I complex membership is the central VPS28 cellular-component annotation. Reason: VPS28 is a constitutive ESCRT-I subunit in TSG101-VPS28-VPS37-MVB12/UBAP variant complexes. Supporting Evidence: file:human/VPS28/VPS28-uniprot.txt Component of the ESCRT-I complex file:human/VPS28/VPS28-uniprot.txt which consists of TSG101, VPS28, a VPS37 PMID:18005716 All ESCRT-I complexes contain three PMID:18005716 TSG101, VPS28, and VPS37 PMID:20654576 comprises a heterotetramer of TSG101 |
| GO:0005886 plasma membrane | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: plasma membrane is supported as a context but is not the core VPS28 proteostasis function. Reason: Plasma-membrane viral budding and extracellular vesicle/exosome contexts use ESCRT machinery but are secondary to the core VPS28 ESCRT-I endosomal sorting and PN autophagophore-sealing role. Supporting Evidence: PMID:18005716 plays essential roles in HIV budding and endosomal protein sorting PMID:20588296 viral budding, cytokinesis and, probably, autophagy file:human/VPS28/VPS28-uniprot.txt Cell membrane |
| GO:0016236 macroautophagy | IEA GO_REF:0000117 | MODIFY | Summary: Macroautophagy is too broad for the VPS28 ESCRT-I autophagy role. Reason: The direct VPS28-linked evidence concerns ESCRT-I helical assembly during phagophore/autophagosome closure, so GO:0000045 autophagosome assembly is the better term. Proposed replacements: autophagosome assembly Supporting Evidence: PMID:31519728 ESCRT-I subunit VPS28 and CHMP2A PMID:31519728 phagophore closure in mammalian cells PMID:32424346 ESCRT-I helical interface is required for autophagosome closure PMID:32424346 blocks filament formation in vitro and autophagosome closure |
| GO:0031902 late endosome membrane | IEA GO_REF:0000044 | ACCEPT | Summary: late endosome membrane localization is supported and relevant to VPS28/ESCRT-I function. Reason: VPS28 is a soluble ESCRT-I component that is recruited to endosomal membranes during cargo sorting and MVB-related ESCRT activity. Supporting Evidence: PMID:11134028 TSG101 and hVPS28 are predominantly cytosolic PMID:11134028 translocated to the surface of these vacuoles PMID:11916981 TSG101 and VPS28 are localized to ubiquitin-rich endosomes file:human/VPS28/VPS28-uniprot.txt Late CC endosome membrane |
| GO:0032509 endosome transport via multivesicular body sorting pathway | IEA GO_REF:0000002 | ACCEPT | Summary: endosome transport via multivesicular body sorting pathway is supported as part of the core ESCRT-I endosomal cargo-sorting role. Reason: VPS28/ESCRT-I supports ubiquitin-dependent endosomal receptor/cargo sorting into MVBs and delivery toward lysosomal degradation. Supporting Evidence: PMID:11134028 directly involved in endosomal sorting PMID:11916981 TSG101 and VPS28 are localized to ubiquitin-rich endosomes PMID:11916981 antibodies to VPS28 specifically impair EGF degradation PMID:21757351 required for sorting EGFR to the MVB file:human/VPS28/VPS28-uniprot.txt Component of the ESCRT-I complex, a regulator of vesicular |
| GO:0036258 multivesicular body assembly | IEA GO_REF:0000117 | ACCEPT | Summary: multivesicular body assembly is supported as part of the core ESCRT-I endosomal cargo-sorting role. Reason: VPS28/ESCRT-I supports ubiquitin-dependent endosomal receptor/cargo sorting into MVBs and delivery toward lysosomal degradation. Supporting Evidence: PMID:11134028 directly involved in endosomal sorting PMID:11916981 TSG101 and VPS28 are localized to ubiquitin-rich endosomes PMID:11916981 antibodies to VPS28 specifically impair EGF degradation PMID:21757351 required for sorting EGFR to the MVB file:human/VPS28/VPS28-uniprot.txt Component of the ESCRT-I complex, a regulator of vesicular |
| GO:0039702 viral budding via host ESCRT complex | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: viral budding via host ESCRT complex is supported as a context but is not the core VPS28 proteostasis function. Reason: Plasma-membrane viral budding and extracellular vesicle/exosome contexts use ESCRT machinery but are secondary to the core VPS28 ESCRT-I endosomal sorting and PN autophagophore-sealing role. Supporting Evidence: PMID:18005716 plays essential roles in HIV budding and endosomal protein sorting PMID:20588296 viral budding, cytokinesis and, probably, autophagy file:human/VPS28/VPS28-uniprot.txt Cell membrane |
| GO:0005515 protein binding | IPI PMID:16189514 Towards a proteome-scale map of the human protein-protein in... | MARK AS OVER ANNOTATED | Summary: Protein binding is too generic to represent VPS28 function. Reason: The informative function is ESCRT-I complex membership and ESCRT-I-mediated endosomal sorting/membrane remodeling, not generic protein binding from interaction assays. Proposed replacements: ESCRT I complex multivesicular body assembly Supporting Evidence: file:human/VPS28/VPS28-uniprot.txt Component of the ESCRT-I complex file:human/VPS28/VPS28-uniprot.txt which consists of TSG101, VPS28, a VPS37 PMID:18005716 All ESCRT-I complexes contain three PMID:18005716 TSG101, VPS28, and VPS37 PMID:20654576 comprises a heterotetramer of TSG101 PMID:11134028 directly involved in endosomal sorting PMID:11916981 TSG101 and VPS28 are localized to ubiquitin-rich endosomes PMID:11916981 antibodies to VPS28 specifically impair EGF degradation PMID:21757351 required for sorting EGFR to the MVB file:human/VPS28/VPS28-uniprot.txt Component of the ESCRT-I complex, a regulator of vesicular |
| GO:0005515 protein binding | IPI PMID:19060904 An empirical framework for binary interactome mapping. | MARK AS OVER ANNOTATED | Summary: Protein binding is too generic to represent VPS28 function. Reason: The informative function is ESCRT-I complex membership and ESCRT-I-mediated endosomal sorting/membrane remodeling, not generic protein binding from interaction assays. Proposed replacements: ESCRT I complex multivesicular body assembly Supporting Evidence: file:human/VPS28/VPS28-uniprot.txt Component of the ESCRT-I complex file:human/VPS28/VPS28-uniprot.txt which consists of TSG101, VPS28, a VPS37 PMID:18005716 All ESCRT-I complexes contain three PMID:18005716 TSG101, VPS28, and VPS37 PMID:20654576 comprises a heterotetramer of TSG101 PMID:11134028 directly involved in endosomal sorting PMID:11916981 TSG101 and VPS28 are localized to ubiquitin-rich endosomes PMID:11916981 antibodies to VPS28 specifically impair EGF degradation PMID:21757351 required for sorting EGFR to the MVB file:human/VPS28/VPS28-uniprot.txt Component of the ESCRT-I complex, a regulator of vesicular |
| GO:0005515 protein binding | IPI PMID:21516116 Next-generation sequencing to generate interactome datasets. | MARK AS OVER ANNOTATED | Summary: Protein binding is too generic to represent VPS28 function. Reason: The informative function is ESCRT-I complex membership and ESCRT-I-mediated endosomal sorting/membrane remodeling, not generic protein binding from interaction assays. Proposed replacements: ESCRT I complex multivesicular body assembly Supporting Evidence: file:human/VPS28/VPS28-uniprot.txt Component of the ESCRT-I complex file:human/VPS28/VPS28-uniprot.txt which consists of TSG101, VPS28, a VPS37 PMID:18005716 All ESCRT-I complexes contain three PMID:18005716 TSG101, VPS28, and VPS37 PMID:20654576 comprises a heterotetramer of TSG101 PMID:11134028 directly involved in endosomal sorting PMID:11916981 TSG101 and VPS28 are localized to ubiquitin-rich endosomes PMID:11916981 antibodies to VPS28 specifically impair EGF degradation PMID:21757351 required for sorting EGFR to the MVB file:human/VPS28/VPS28-uniprot.txt Component of the ESCRT-I complex, a regulator of vesicular |
| 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 VPS28 function. Reason: The informative function is ESCRT-I complex membership and ESCRT-I-mediated endosomal sorting/membrane remodeling, not generic protein binding from interaction assays. Proposed replacements: ESCRT I complex multivesicular body assembly Supporting Evidence: file:human/VPS28/VPS28-uniprot.txt Component of the ESCRT-I complex file:human/VPS28/VPS28-uniprot.txt which consists of TSG101, VPS28, a VPS37 PMID:18005716 All ESCRT-I complexes contain three PMID:18005716 TSG101, VPS28, and VPS37 PMID:20654576 comprises a heterotetramer of TSG101 PMID:11134028 directly involved in endosomal sorting PMID:11916981 TSG101 and VPS28 are localized to ubiquitin-rich endosomes PMID:11916981 antibodies to VPS28 specifically impair EGF degradation PMID:21757351 required for sorting EGFR to the MVB file:human/VPS28/VPS28-uniprot.txt Component of the ESCRT-I complex, a regulator of vesicular |
| GO:0005515 protein binding | IPI PMID:25959826 Quantitative interaction proteomics of neurodegenerative dis... | MARK AS OVER ANNOTATED | Summary: Protein binding is too generic to represent VPS28 function. Reason: The informative function is ESCRT-I complex membership and ESCRT-I-mediated endosomal sorting/membrane remodeling, not generic protein binding from interaction assays. Proposed replacements: ESCRT I complex multivesicular body assembly Supporting Evidence: file:human/VPS28/VPS28-uniprot.txt Component of the ESCRT-I complex file:human/VPS28/VPS28-uniprot.txt which consists of TSG101, VPS28, a VPS37 PMID:18005716 All ESCRT-I complexes contain three PMID:18005716 TSG101, VPS28, and VPS37 PMID:20654576 comprises a heterotetramer of TSG101 PMID:11134028 directly involved in endosomal sorting PMID:11916981 TSG101 and VPS28 are localized to ubiquitin-rich endosomes PMID:11916981 antibodies to VPS28 specifically impair EGF degradation PMID:21757351 required for sorting EGFR to the MVB file:human/VPS28/VPS28-uniprot.txt Component of the ESCRT-I complex, a regulator of vesicular |
| GO:0005515 protein binding | IPI PMID:26871637 Widespread Expansion of Protein Interaction Capabilities by ... | MARK AS OVER ANNOTATED | Summary: Protein binding is too generic to represent VPS28 function. Reason: The informative function is ESCRT-I complex membership and ESCRT-I-mediated endosomal sorting/membrane remodeling, not generic protein binding from interaction assays. Proposed replacements: ESCRT I complex multivesicular body assembly Supporting Evidence: file:human/VPS28/VPS28-uniprot.txt Component of the ESCRT-I complex file:human/VPS28/VPS28-uniprot.txt which consists of TSG101, VPS28, a VPS37 PMID:18005716 All ESCRT-I complexes contain three PMID:18005716 TSG101, VPS28, and VPS37 PMID:20654576 comprises a heterotetramer of TSG101 PMID:11134028 directly involved in endosomal sorting PMID:11916981 TSG101 and VPS28 are localized to ubiquitin-rich endosomes PMID:11916981 antibodies to VPS28 specifically impair EGF degradation PMID:21757351 required for sorting EGFR to the MVB file:human/VPS28/VPS28-uniprot.txt Component of the ESCRT-I complex, a regulator of vesicular |
| 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 VPS28 function. Reason: The informative function is ESCRT-I complex membership and ESCRT-I-mediated endosomal sorting/membrane remodeling, not generic protein binding from interaction assays. Proposed replacements: ESCRT I complex multivesicular body assembly Supporting Evidence: file:human/VPS28/VPS28-uniprot.txt Component of the ESCRT-I complex file:human/VPS28/VPS28-uniprot.txt which consists of TSG101, VPS28, a VPS37 PMID:18005716 All ESCRT-I complexes contain three PMID:18005716 TSG101, VPS28, and VPS37 PMID:20654576 comprises a heterotetramer of TSG101 PMID:11134028 directly involved in endosomal sorting PMID:11916981 TSG101 and VPS28 are localized to ubiquitin-rich endosomes PMID:11916981 antibodies to VPS28 specifically impair EGF degradation PMID:21757351 required for sorting EGFR to the MVB file:human/VPS28/VPS28-uniprot.txt Component of the ESCRT-I complex, a regulator of vesicular |
| GO:0005515 protein binding | IPI PMID:31515488 Extensive disruption of protein interactions by genetic vari... | MARK AS OVER ANNOTATED | Summary: Protein binding is too generic to represent VPS28 function. Reason: The informative function is ESCRT-I complex membership and ESCRT-I-mediated endosomal sorting/membrane remodeling, not generic protein binding from interaction assays. Proposed replacements: ESCRT I complex multivesicular body assembly Supporting Evidence: file:human/VPS28/VPS28-uniprot.txt Component of the ESCRT-I complex file:human/VPS28/VPS28-uniprot.txt which consists of TSG101, VPS28, a VPS37 PMID:18005716 All ESCRT-I complexes contain three PMID:18005716 TSG101, VPS28, and VPS37 PMID:20654576 comprises a heterotetramer of TSG101 PMID:11134028 directly involved in endosomal sorting PMID:11916981 TSG101 and VPS28 are localized to ubiquitin-rich endosomes PMID:11916981 antibodies to VPS28 specifically impair EGF degradation PMID:21757351 required for sorting EGFR to the MVB file:human/VPS28/VPS28-uniprot.txt Component of the ESCRT-I complex, a regulator of vesicular |
| GO:0005515 protein binding | IPI PMID:32814053 Interactome Mapping Provides a Network of Neurodegenerative ... | MARK AS OVER ANNOTATED | Summary: Protein binding is too generic to represent VPS28 function. Reason: The informative function is ESCRT-I complex membership and ESCRT-I-mediated endosomal sorting/membrane remodeling, not generic protein binding from interaction assays. Proposed replacements: ESCRT I complex multivesicular body assembly Supporting Evidence: file:human/VPS28/VPS28-uniprot.txt Component of the ESCRT-I complex file:human/VPS28/VPS28-uniprot.txt which consists of TSG101, VPS28, a VPS37 PMID:18005716 All ESCRT-I complexes contain three PMID:18005716 TSG101, VPS28, and VPS37 PMID:20654576 comprises a heterotetramer of TSG101 PMID:11134028 directly involved in endosomal sorting PMID:11916981 TSG101 and VPS28 are localized to ubiquitin-rich endosomes PMID:11916981 antibodies to VPS28 specifically impair EGF degradation PMID:21757351 required for sorting EGFR to the MVB file:human/VPS28/VPS28-uniprot.txt Component of the ESCRT-I complex, a regulator of vesicular |
| 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 VPS28 function. Reason: The informative function is ESCRT-I complex membership and ESCRT-I-mediated endosomal sorting/membrane remodeling, not generic protein binding from interaction assays. Proposed replacements: ESCRT I complex multivesicular body assembly Supporting Evidence: file:human/VPS28/VPS28-uniprot.txt Component of the ESCRT-I complex file:human/VPS28/VPS28-uniprot.txt which consists of TSG101, VPS28, a VPS37 PMID:18005716 All ESCRT-I complexes contain three PMID:18005716 TSG101, VPS28, and VPS37 PMID:20654576 comprises a heterotetramer of TSG101 PMID:11134028 directly involved in endosomal sorting PMID:11916981 TSG101 and VPS28 are localized to ubiquitin-rich endosomes PMID:11916981 antibodies to VPS28 specifically impair EGF degradation PMID:21757351 required for sorting EGFR to the MVB file:human/VPS28/VPS28-uniprot.txt Component of the ESCRT-I complex, a regulator of vesicular |
| GO:0005515 protein binding | IPI PMID:35271311 OpenCell: Endogenous tagging for the cartography of human ce... | MARK AS OVER ANNOTATED | Summary: Protein binding is too generic to represent VPS28 function. Reason: The informative function is ESCRT-I complex membership and ESCRT-I-mediated endosomal sorting/membrane remodeling, not generic protein binding from interaction assays. Proposed replacements: ESCRT I complex multivesicular body assembly Supporting Evidence: file:human/VPS28/VPS28-uniprot.txt Component of the ESCRT-I complex file:human/VPS28/VPS28-uniprot.txt which consists of TSG101, VPS28, a VPS37 PMID:18005716 All ESCRT-I complexes contain three PMID:18005716 TSG101, VPS28, and VPS37 PMID:20654576 comprises a heterotetramer of TSG101 PMID:11134028 directly involved in endosomal sorting PMID:11916981 TSG101 and VPS28 are localized to ubiquitin-rich endosomes PMID:11916981 antibodies to VPS28 specifically impair EGF degradation PMID:21757351 required for sorting EGFR to the MVB file:human/VPS28/VPS28-uniprot.txt Component of the ESCRT-I complex, a regulator of vesicular |
| GO:0005829 cytosol | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: cytosol localization is supported but broad and non-core. Reason: VPS28 is predominantly cytosolic as a soluble ESCRT-I component before membrane recruitment, but the core proteostasis function is ESCRT-I activity at endosomal/phagophore membranes. Supporting Evidence: PMID:11134028 cytosolic protein that interacts with TSG101/mammalian VPS23 PMID:11134028 TSG101 and hVPS28 are predominantly cytosolic |
| 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 VPS28 cellular-component annotation. Reason: VPS28 is a constitutive ESCRT-I subunit in TSG101-VPS28-VPS37-MVB12/UBAP variant complexes. Supporting Evidence: file:human/VPS28/VPS28-uniprot.txt Component of the ESCRT-I complex file:human/VPS28/VPS28-uniprot.txt which consists of TSG101, VPS28, a VPS37 PMID:18005716 All ESCRT-I complexes contain three PMID:18005716 TSG101, VPS28, and VPS37 PMID:20654576 comprises a heterotetramer of TSG101 |
| GO:0000813 ESCRT I complex | IPI PMID:21757351 UBAP1 is a component of an endosome-specific ESCRT-I complex... | ACCEPT | Summary: ESCRT-I complex membership is the central VPS28 cellular-component annotation. Reason: VPS28 is a constitutive ESCRT-I subunit in TSG101-VPS28-VPS37-MVB12/UBAP variant complexes. Supporting Evidence: file:human/VPS28/VPS28-uniprot.txt Component of the ESCRT-I complex file:human/VPS28/VPS28-uniprot.txt which consists of TSG101, VPS28, a VPS37 PMID:18005716 All ESCRT-I complexes contain three PMID:18005716 TSG101, VPS28, and VPS37 PMID:20654576 comprises a heterotetramer of TSG101 |
| 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 VPS28 cellular-component annotation. Reason: VPS28 is a constitutive ESCRT-I subunit in TSG101-VPS28-VPS37-MVB12/UBAP variant complexes. Supporting Evidence: file:human/VPS28/VPS28-uniprot.txt Component of the ESCRT-I complex file:human/VPS28/VPS28-uniprot.txt which consists of TSG101, VPS28, a VPS37 PMID:18005716 All ESCRT-I complexes contain three PMID:18005716 TSG101, VPS28, and VPS37 PMID:20654576 comprises a heterotetramer of TSG101 |
| 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 VPS28/ESCRT-I function. Reason: VPS28 is a soluble ESCRT-I component that is recruited to endosomal membranes during cargo sorting and MVB-related ESCRT activity. Supporting Evidence: PMID:11134028 TSG101 and hVPS28 are predominantly cytosolic PMID:11134028 translocated to the surface of these vacuoles PMID:11916981 TSG101 and VPS28 are localized to ubiquitin-rich endosomes file:human/VPS28/VPS28-uniprot.txt Late CC endosome membrane |
| 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 the core ESCRT-I endosomal cargo-sorting role. Reason: VPS28/ESCRT-I supports ubiquitin-dependent endosomal receptor/cargo sorting into MVBs and delivery toward lysosomal degradation. Supporting Evidence: PMID:11134028 directly involved in endosomal sorting PMID:11916981 TSG101 and VPS28 are localized to ubiquitin-rich endosomes PMID:11916981 antibodies to VPS28 specifically impair EGF degradation PMID:21757351 required for sorting EGFR to the MVB file:human/VPS28/VPS28-uniprot.txt Component of the ESCRT-I complex, a regulator of vesicular |
| 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 the core ESCRT-I endosomal cargo-sorting role. Reason: VPS28/ESCRT-I supports ubiquitin-dependent endosomal receptor/cargo sorting into MVBs and delivery toward lysosomal degradation. Supporting Evidence: PMID:11134028 directly involved in endosomal sorting PMID:11916981 TSG101 and VPS28 are localized to ubiquitin-rich endosomes PMID:11916981 antibodies to VPS28 specifically impair EGF degradation PMID:21757351 required for sorting EGFR to the MVB file:human/VPS28/VPS28-uniprot.txt Component of the ESCRT-I complex, a regulator of vesicular |
| GO:0090148 membrane fission | NAS PMID:32424346 A helical assembly of human ESCRT-I scaffolds reverse-topolo... | ACCEPT | Summary: Membrane fission is supported for ESCRT-I reverse-topology membrane remodeling. Reason: ESCRT-I scaffolds reverse-topology membrane remodeling; VPS28 helical-interface mutations disrupt ESCRT-I filament assembly and ESCRT-dependent sealing contexts. Supporting Evidence: PMID:20588296 ESCRT-I and ESCRT-II direct membrane budding away from the cytosol PMID:32424346 A helical assembly of human ESCRT-I scaffolds reverse-topology membrane scission PMID:32424346 VPS28 helical interface residues blocks filament formation in vitro and autophagosome |
| GO:0005515 protein binding | IPI PMID:15218037 The human endosomal sorting complex required for transport (... | MARK AS OVER ANNOTATED | Summary: Protein binding is too generic to represent VPS28 function. Reason: The informative function is ESCRT-I complex membership and ESCRT-I-mediated endosomal sorting/membrane remodeling, not generic protein binding from interaction assays. Proposed replacements: ESCRT I complex multivesicular body assembly Supporting Evidence: file:human/VPS28/VPS28-uniprot.txt Component of the ESCRT-I complex file:human/VPS28/VPS28-uniprot.txt which consists of TSG101, VPS28, a VPS37 PMID:18005716 All ESCRT-I complexes contain three PMID:18005716 TSG101, VPS28, and VPS37 PMID:20654576 comprises a heterotetramer of TSG101 PMID:11134028 directly involved in endosomal sorting PMID:11916981 TSG101 and VPS28 are localized to ubiquitin-rich endosomes PMID:11916981 antibodies to VPS28 specifically impair EGF degradation PMID:21757351 required for sorting EGFR to the MVB file:human/VPS28/VPS28-uniprot.txt Component of the ESCRT-I complex, a regulator of vesicular |
| GO:0016236 macroautophagy | TAS PMID:20588296 Membrane budding and scission by the ESCRT machinery: it's a... | MODIFY | Summary: Macroautophagy is too broad for the VPS28 ESCRT-I autophagy role. Reason: The direct VPS28-linked evidence concerns ESCRT-I helical assembly during phagophore/autophagosome closure, so GO:0000045 autophagosome assembly is the better term. Proposed replacements: autophagosome assembly Supporting Evidence: PMID:31519728 ESCRT-I subunit VPS28 and CHMP2A PMID:31519728 phagophore closure in mammalian cells PMID:32424346 ESCRT-I helical interface is required for autophagosome closure PMID:32424346 blocks filament formation in vitro and autophagosome closure |
| 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 VPS28 cellular-component annotation. Reason: VPS28 is a constitutive ESCRT-I subunit in TSG101-VPS28-VPS37-MVB12/UBAP variant complexes. Supporting Evidence: file:human/VPS28/VPS28-uniprot.txt Component of the ESCRT-I complex file:human/VPS28/VPS28-uniprot.txt which consists of TSG101, VPS28, a VPS37 PMID:18005716 All ESCRT-I complexes contain three PMID:18005716 TSG101, VPS28, and VPS37 PMID:20654576 comprises a heterotetramer of TSG101 |
| 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 the core ESCRT-I endosomal cargo-sorting role. Reason: VPS28/ESCRT-I supports ubiquitin-dependent endosomal receptor/cargo sorting into MVBs and delivery toward lysosomal degradation. Supporting Evidence: PMID:11134028 directly involved in endosomal sorting PMID:11916981 TSG101 and VPS28 are localized to ubiquitin-rich endosomes PMID:11916981 antibodies to VPS28 specifically impair EGF degradation PMID:21757351 required for sorting EGFR to the MVB file:human/VPS28/VPS28-uniprot.txt Component of the ESCRT-I complex, a regulator of vesicular |
| 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 supported as a context but is not the core VPS28 proteostasis function. Reason: Plasma-membrane viral budding and extracellular vesicle/exosome contexts use ESCRT machinery but are secondary to the core VPS28 ESCRT-I endosomal sorting and PN autophagophore-sealing role. Supporting Evidence: PMID:18005716 plays essential roles in HIV budding and endosomal protein sorting PMID:20588296 viral budding, cytokinesis and, probably, autophagy file:human/VPS28/VPS28-uniprot.txt Cell membrane |
| 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 VPS28 cellular-component annotation. Reason: VPS28 is a constitutive ESCRT-I subunit in TSG101-VPS28-VPS37-MVB12/UBAP variant complexes. Supporting Evidence: file:human/VPS28/VPS28-uniprot.txt Component of the ESCRT-I complex file:human/VPS28/VPS28-uniprot.txt which consists of TSG101, VPS28, a VPS37 PMID:18005716 All ESCRT-I complexes contain three PMID:18005716 TSG101, VPS28, and VPS37 PMID:20654576 comprises a heterotetramer of TSG101 |
| GO:0005768 endosome | IDA PMID:17940959 Involvement of vacuolar protein sorting pathway in Ebola vir... | ACCEPT | Summary: endosome localization is supported and relevant to VPS28/ESCRT-I function. Reason: VPS28 is a soluble ESCRT-I component that is recruited to endosomal membranes during cargo sorting and MVB-related ESCRT activity. Supporting Evidence: PMID:11134028 TSG101 and hVPS28 are predominantly cytosolic PMID:11134028 translocated to the surface of these vacuoles PMID:11916981 TSG101 and VPS28 are localized to ubiquitin-rich endosomes file:human/VPS28/VPS28-uniprot.txt Late CC endosome membrane |
| GO:0005886 plasma membrane | IDA PMID:17940959 Involvement of vacuolar protein sorting pathway in Ebola vir... | KEEP AS NON CORE | Summary: plasma membrane is supported as a context but is not the core VPS28 proteostasis function. Reason: Plasma-membrane viral budding and extracellular vesicle/exosome contexts use ESCRT machinery but are secondary to the core VPS28 ESCRT-I endosomal sorting and PN autophagophore-sealing role. Supporting Evidence: PMID:18005716 plays essential roles in HIV budding and endosomal protein sorting PMID:20588296 viral budding, cytokinesis and, probably, autophagy file:human/VPS28/VPS28-uniprot.txt Cell membrane |
| GO:0045732 positive regulation of protein catabolic process | IMP PMID:11916981 Mammalian class E vps proteins recognize ubiquitin and act i... | MODIFY | Summary: Positive regulation of protein catabolic process is too broad for the VPS28 evidence. Reason: The PMID:11916981 evidence specifically concerns EGF/EGFR degradation through ubiquitin-dependent endosomal sorting rather than a general protein-catabolic regulatory function. Proposed replacements: positive regulation of ubiquitin-dependent endocytosis ubiquitin-dependent protein catabolic process via the multivesicular body sorting pathway Supporting Evidence: PMID:11134028 directly involved in endosomal sorting PMID:11916981 TSG101 and VPS28 are localized to ubiquitin-rich endosomes PMID:11916981 antibodies to VPS28 specifically impair EGF degradation PMID:21757351 required for sorting EGFR to the MVB file:human/VPS28/VPS28-uniprot.txt Component of the ESCRT-I complex, a regulator of vesicular |
| GO:2000397 positive regulation of ubiquitin-dependent endocytosis | IMP PMID:11916981 Mammalian class E vps proteins recognize ubiquitin and act i... | ACCEPT | Summary: positive regulation of ubiquitin-dependent endocytosis is supported as part of the core ESCRT-I endosomal cargo-sorting role. Reason: VPS28/ESCRT-I supports ubiquitin-dependent endosomal receptor/cargo sorting into MVBs and delivery toward lysosomal degradation. Supporting Evidence: PMID:11134028 directly involved in endosomal sorting PMID:11916981 TSG101 and VPS28 are localized to ubiquitin-rich endosomes PMID:11916981 antibodies to VPS28 specifically impair EGF degradation PMID:21757351 required for sorting EGFR to the MVB file:human/VPS28/VPS28-uniprot.txt Component of the ESCRT-I complex, a regulator of vesicular |
| GO:0005769 early endosome | IDA PMID:11916981 Mammalian class E vps proteins recognize ubiquitin and act i... | ACCEPT | Summary: early endosome localization is supported and relevant to VPS28/ESCRT-I function. Reason: VPS28 is a soluble ESCRT-I component that is recruited to endosomal membranes during cargo sorting and MVB-related ESCRT activity. Supporting Evidence: PMID:11134028 TSG101 and hVPS28 are predominantly cytosolic PMID:11134028 translocated to the surface of these vacuoles PMID:11916981 TSG101 and VPS28 are localized to ubiquitin-rich endosomes file:human/VPS28/VPS28-uniprot.txt Late CC endosome membrane |
| GO:0043130 ubiquitin binding | IDA PMID:11916981 Mammalian class E vps proteins recognize ubiquitin and act i... | MARK AS OVER ANNOTATED | Summary: Direct ubiquitin binding is over-annotated for VPS28. Reason: The cited paper shows the TSG101-hVPS28 complex binds ubiquitin, but isolated hVPS28 does not; the binding is attributed to TSG101 UEV-domain recognition, so VPS28 should not be curated as directly enabling ubiquitin binding. Proposed replacements: ESCRT I complex ubiquitin-dependent protein catabolic process via the multivesicular body sorting pathway Supporting Evidence: PMID:11916981 Both TSG101 and hVPS28 bound specifically to ubiquitin-agarose PMID:11916981 hVPS28 did not bind to ubiquitin-agarose PMID:11916981 complex binding to ubiquitin via the Ubc domain of TSG101 |
| GO:0005515 protein binding | IPI PMID:11134028 TSG101/mammalian VPS23 and mammalian VPS28 interact directly... | MARK AS OVER ANNOTATED | Summary: Protein binding is too generic to represent VPS28 function. Reason: The informative function is ESCRT-I complex membership and ESCRT-I-mediated endosomal sorting/membrane remodeling, not generic protein binding from interaction assays. Proposed replacements: ESCRT I complex multivesicular body assembly Supporting Evidence: file:human/VPS28/VPS28-uniprot.txt Component of the ESCRT-I complex file:human/VPS28/VPS28-uniprot.txt which consists of TSG101, VPS28, a VPS37 PMID:18005716 All ESCRT-I complexes contain three PMID:18005716 TSG101, VPS28, and VPS37 PMID:20654576 comprises a heterotetramer of TSG101 PMID:11134028 directly involved in endosomal sorting PMID:11916981 TSG101 and VPS28 are localized to ubiquitin-rich endosomes PMID:11916981 antibodies to VPS28 specifically impair EGF degradation PMID:21757351 required for sorting EGFR to the MVB file:human/VPS28/VPS28-uniprot.txt Component of the ESCRT-I complex, a regulator of vesicular |
| GO:0010008 endosome membrane | IDA PMID:11134028 TSG101/mammalian VPS23 and mammalian VPS28 interact directly... | ACCEPT | Summary: endosome membrane localization is supported and relevant to VPS28/ESCRT-I function. Reason: VPS28 is a soluble ESCRT-I component that is recruited to endosomal membranes during cargo sorting and MVB-related ESCRT activity. Supporting Evidence: PMID:11134028 TSG101 and hVPS28 are predominantly cytosolic PMID:11134028 translocated to the surface of these vacuoles PMID:11916981 TSG101 and VPS28 are localized to ubiquitin-rich endosomes file:human/VPS28/VPS28-uniprot.txt Late CC endosome membrane |
| 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 context but is not the core VPS28 proteostasis function. Reason: Plasma-membrane viral budding and extracellular vesicle/exosome contexts use ESCRT machinery but are secondary to the core VPS28 ESCRT-I endosomal sorting and PN autophagophore-sealing role. Supporting Evidence: PMID:18005716 plays essential roles in HIV budding and endosomal protein sorting PMID:20588296 viral budding, cytokinesis and, probably, autophagy file:human/VPS28/VPS28-uniprot.txt Cell membrane |
| GO:0005515 protein binding | IPI PMID:14519844 Divergent retroviral late-budding domains recruit vacuolar p... | MARK AS OVER ANNOTATED | Summary: Protein binding is too generic to represent VPS28 function. Reason: The informative function is ESCRT-I complex membership and ESCRT-I-mediated endosomal sorting/membrane remodeling, not generic protein binding from interaction assays. Proposed replacements: ESCRT I complex multivesicular body assembly Supporting Evidence: file:human/VPS28/VPS28-uniprot.txt Component of the ESCRT-I complex file:human/VPS28/VPS28-uniprot.txt which consists of TSG101, VPS28, a VPS37 PMID:18005716 All ESCRT-I complexes contain three PMID:18005716 TSG101, VPS28, and VPS37 PMID:20654576 comprises a heterotetramer of TSG101 PMID:11134028 directly involved in endosomal sorting PMID:11916981 TSG101 and VPS28 are localized to ubiquitin-rich endosomes PMID:11916981 antibodies to VPS28 specifically impair EGF degradation PMID:21757351 required for sorting EGFR to the MVB file:human/VPS28/VPS28-uniprot.txt Component of the ESCRT-I complex, a regulator of vesicular |
| GO:0005515 protein binding | IPI PMID:14505570 The protein network of HIV budding. | MARK AS OVER ANNOTATED | Summary: Protein binding is too generic to represent VPS28 function. Reason: The informative function is ESCRT-I complex membership and ESCRT-I-mediated endosomal sorting/membrane remodeling, not generic protein binding from interaction assays. Proposed replacements: ESCRT I complex multivesicular body assembly Supporting Evidence: file:human/VPS28/VPS28-uniprot.txt Component of the ESCRT-I complex file:human/VPS28/VPS28-uniprot.txt which consists of TSG101, VPS28, a VPS37 PMID:18005716 All ESCRT-I complexes contain three PMID:18005716 TSG101, VPS28, and VPS37 PMID:20654576 comprises a heterotetramer of TSG101 PMID:11134028 directly involved in endosomal sorting PMID:11916981 TSG101 and VPS28 are localized to ubiquitin-rich endosomes PMID:11916981 antibodies to VPS28 specifically impair EGF degradation PMID:21757351 required for sorting EGFR to the MVB file:human/VPS28/VPS28-uniprot.txt Component of the ESCRT-I complex, a regulator of vesicular |
| 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 VPS28 cellular-component annotation. Reason: VPS28 is a constitutive ESCRT-I subunit in TSG101-VPS28-VPS37-MVB12/UBAP variant complexes. Supporting Evidence: file:human/VPS28/VPS28-uniprot.txt Component of the ESCRT-I complex file:human/VPS28/VPS28-uniprot.txt which consists of TSG101, VPS28, a VPS37 PMID:18005716 All ESCRT-I complexes contain three PMID:18005716 TSG101, VPS28, and VPS37 PMID:20654576 comprises a heterotetramer of TSG101 |
| 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 VPS28 cellular-component annotation. Reason: VPS28 is a constitutive ESCRT-I subunit in TSG101-VPS28-VPS37-MVB12/UBAP variant complexes. Supporting Evidence: file:human/VPS28/VPS28-uniprot.txt Component of the ESCRT-I complex file:human/VPS28/VPS28-uniprot.txt which consists of TSG101, VPS28, a VPS37 PMID:18005716 All ESCRT-I complexes contain three PMID:18005716 TSG101, VPS28, and VPS37 PMID:20654576 comprises a heterotetramer of TSG101 |
| 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 the core ESCRT-I endosomal cargo-sorting role. Reason: VPS28/ESCRT-I supports ubiquitin-dependent endosomal receptor/cargo sorting into MVBs and delivery toward lysosomal degradation. Supporting Evidence: PMID:11134028 directly involved in endosomal sorting PMID:11916981 TSG101 and VPS28 are localized to ubiquitin-rich endosomes PMID:11916981 antibodies to VPS28 specifically impair EGF degradation PMID:21757351 required for sorting EGFR to the MVB file:human/VPS28/VPS28-uniprot.txt Component of the ESCRT-I complex, a regulator of vesicular |
| GO:0070062 extracellular exosome | HDA PMID:19199708 Proteomic analysis of human parotid gland exosomes by multid... | KEEP AS NON CORE | Summary: extracellular exosome is supported as a context but is not the core VPS28 proteostasis function. Reason: Plasma-membrane viral budding and extracellular vesicle/exosome contexts use ESCRT machinery but are secondary to the core VPS28 ESCRT-I endosomal sorting and PN autophagophore-sealing role. Supporting Evidence: PMID:18005716 plays essential roles in HIV budding and endosomal protein sorting PMID:20588296 viral budding, cytokinesis and, probably, autophagy file:human/VPS28/VPS28-uniprot.txt Cell membrane |
| 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 context but is not the core VPS28 proteostasis function. Reason: Plasma-membrane viral budding and extracellular vesicle/exosome contexts use ESCRT machinery but are secondary to the core VPS28 ESCRT-I endosomal sorting and PN autophagophore-sealing role. Supporting Evidence: PMID:18005716 plays essential roles in HIV budding and endosomal protein sorting PMID:20588296 viral budding, cytokinesis and, probably, autophagy file:human/VPS28/VPS28-uniprot.txt Cell membrane |
| GO:0070062 extracellular exosome | HDA PMID:20458337 MHC class II-associated proteins in B-cell exosomes and pote... | KEEP AS NON CORE | Summary: extracellular exosome is supported as a context but is not the core VPS28 proteostasis function. Reason: Plasma-membrane viral budding and extracellular vesicle/exosome contexts use ESCRT machinery but are secondary to the core VPS28 ESCRT-I endosomal sorting and PN autophagophore-sealing role. Supporting Evidence: PMID:18005716 plays essential roles in HIV budding and endosomal protein sorting PMID:20588296 viral budding, cytokinesis and, probably, autophagy file:human/VPS28/VPS28-uniprot.txt Cell membrane |
| GO:0000813 ESCRT I complex | IDA PMID:21757351 UBAP1 is a component of an endosome-specific ESCRT-I complex... | ACCEPT | Summary: ESCRT-I complex membership is the central VPS28 cellular-component annotation. Reason: VPS28 is a constitutive ESCRT-I subunit in TSG101-VPS28-VPS37-MVB12/UBAP variant complexes. Supporting Evidence: file:human/VPS28/VPS28-uniprot.txt Component of the ESCRT-I complex file:human/VPS28/VPS28-uniprot.txt which consists of TSG101, VPS28, a VPS37 PMID:18005716 All ESCRT-I complexes contain three PMID:18005716 TSG101, VPS28, and VPS37 PMID:20654576 comprises a heterotetramer of TSG101 |
| GO:0043162 ubiquitin-dependent protein catabolic process via the multivesicular body sorting pathway | IMP PMID:21757351 UBAP1 is a component of an endosome-specific ESCRT-I complex... | ACCEPT | Summary: ubiquitin-dependent protein catabolic process via the multivesicular body sorting pathway is supported as part of the core ESCRT-I endosomal cargo-sorting role. Reason: VPS28/ESCRT-I supports ubiquitin-dependent endosomal receptor/cargo sorting into MVBs and delivery toward lysosomal degradation. Supporting Evidence: PMID:11134028 directly involved in endosomal sorting PMID:11916981 TSG101 and VPS28 are localized to ubiquitin-rich endosomes PMID:11916981 antibodies to VPS28 specifically impair EGF degradation PMID:21757351 required for sorting EGFR to the MVB file:human/VPS28/VPS28-uniprot.txt Component of the ESCRT-I complex, a regulator of vesicular |
| GO:0010008 endosome membrane | TAS Reactome:R-HSA-184269 | ACCEPT | Summary: endosome membrane localization is supported and relevant to VPS28/ESCRT-I function. Reason: VPS28 is a soluble ESCRT-I component that is recruited to endosomal membranes during cargo sorting and MVB-related ESCRT activity. Supporting Evidence: PMID:11134028 TSG101 and hVPS28 are predominantly cytosolic PMID:11134028 translocated to the surface of these vacuoles PMID:11916981 TSG101 and VPS28 are localized to ubiquitin-rich endosomes file:human/VPS28/VPS28-uniprot.txt Late CC endosome membrane |
| GO:0010008 endosome membrane | TAS Reactome:R-HSA-3149434 | ACCEPT | Summary: endosome membrane localization is supported and relevant to VPS28/ESCRT-I function. Reason: VPS28 is a soluble ESCRT-I component that is recruited to endosomal membranes during cargo sorting and MVB-related ESCRT activity. Supporting Evidence: PMID:11134028 TSG101 and hVPS28 are predominantly cytosolic PMID:11134028 translocated to the surface of these vacuoles PMID:11916981 TSG101 and VPS28 are localized to ubiquitin-rich endosomes file:human/VPS28/VPS28-uniprot.txt Late CC endosome membrane |
| GO:0010008 endosome membrane | TAS Reactome:R-HSA-3159232 | ACCEPT | Summary: endosome membrane localization is supported and relevant to VPS28/ESCRT-I function. Reason: VPS28 is a soluble ESCRT-I component that is recruited to endosomal membranes during cargo sorting and MVB-related ESCRT activity. Supporting Evidence: PMID:11134028 TSG101 and hVPS28 are predominantly cytosolic PMID:11134028 translocated to the surface of these vacuoles PMID:11916981 TSG101 and VPS28 are localized to ubiquitin-rich endosomes file:human/VPS28/VPS28-uniprot.txt Late CC endosome membrane |
| GO:0010008 endosome membrane | TAS Reactome:R-HSA-917696 | ACCEPT | Summary: endosome membrane localization is supported and relevant to VPS28/ESCRT-I function. Reason: VPS28 is a soluble ESCRT-I component that is recruited to endosomal membranes during cargo sorting and MVB-related ESCRT activity. Supporting Evidence: PMID:11134028 TSG101 and hVPS28 are predominantly cytosolic PMID:11134028 translocated to the surface of these vacuoles PMID:11916981 TSG101 and VPS28 are localized to ubiquitin-rich endosomes file:human/VPS28/VPS28-uniprot.txt Late CC endosome membrane |
| GO:0010008 endosome membrane | TAS Reactome:R-HSA-917730 | ACCEPT | Summary: endosome membrane localization is supported and relevant to VPS28/ESCRT-I function. Reason: VPS28 is a soluble ESCRT-I component that is recruited to endosomal membranes during cargo sorting and MVB-related ESCRT activity. Supporting Evidence: PMID:11134028 TSG101 and hVPS28 are predominantly cytosolic PMID:11134028 translocated to the surface of these vacuoles PMID:11916981 TSG101 and VPS28 are localized to ubiquitin-rich endosomes file:human/VPS28/VPS28-uniprot.txt Late CC endosome membrane |
| GO:0005737 cytoplasm | IDA PMID:18077552 Regulation of Tsg101 expression by the steadiness box: a rol... | KEEP AS NON CORE | Summary: cytoplasm localization is supported but broad and non-core. Reason: VPS28 is predominantly cytosolic as a soluble ESCRT-I component before membrane recruitment, but the core proteostasis function is ESCRT-I activity at endosomal/phagophore membranes. Supporting Evidence: PMID:11134028 cytosolic protein that interacts with TSG101/mammalian VPS23 PMID:11134028 TSG101 and hVPS28 are predominantly cytosolic |
| GO:0031397 negative regulation of protein ubiquitination | IDA PMID:18077552 Regulation of Tsg101 expression by the steadiness box: a rol... | MARK AS OVER ANNOTATED | Summary: Negative regulation of protein ubiquitination is a broad over-annotation for VPS28. Reason: The cited evidence is about VPS28/ESCRT-I occupancy limiting TSG101 access to a TSG101-associated ligase, not a general VPS28 ubiquitination-regulatory function. Proposed replacements: ESCRT I complex Supporting Evidence: PMID:18077552 VPS28 is a limiting factor PMID:18077552 presence of the other ESCRT-I proteins |
| GO:0005768 endosome | IDA PMID:11134028 TSG101/mammalian VPS23 and mammalian VPS28 interact directly... | ACCEPT | Summary: endosome localization is supported and relevant to VPS28/ESCRT-I function. Reason: VPS28 is a soluble ESCRT-I component that is recruited to endosomal membranes during cargo sorting and MVB-related ESCRT activity. Supporting Evidence: PMID:11134028 TSG101 and hVPS28 are predominantly cytosolic PMID:11134028 translocated to the surface of these vacuoles PMID:11916981 TSG101 and VPS28 are localized to ubiquitin-rich endosomes file:human/VPS28/VPS28-uniprot.txt Late CC endosome membrane |
| GO:0005829 cytosol | IDA PMID:11134028 TSG101/mammalian VPS23 and mammalian VPS28 interact directly... | KEEP AS NON CORE | Summary: cytosol localization is supported but broad and non-core. Reason: VPS28 is predominantly cytosolic as a soluble ESCRT-I component before membrane recruitment, but the core proteostasis function is ESCRT-I activity at endosomal/phagophore membranes. Supporting Evidence: PMID:11134028 cytosolic protein that interacts with TSG101/mammalian VPS23 PMID:11134028 TSG101 and hVPS28 are predominantly cytosolic |
| GO:0000045 autophagosome assembly | IMP PMID:32424346 A helical assembly of human ESCRT-I scaffolds reverse-topolo... | NEW | Summary: VPS28 should be annotated to autophagosome assembly for ESCRT-I-dependent phagophore closure. Reason: VPS28 helical-interface mutations disrupt ESCRT-I filament assembly and cause an autophagosome closure defect; this is more precise than broad macroautophagy. Supporting Evidence: PMID:31519728 ESCRT-I subunit VPS28 and CHMP2A PMID:31519728 phagophore closure in mammalian cells PMID:32424346 ESCRT-I helical interface is required for autophagosome closure PMID:32424346 blocks filament formation in vitro and autophagosome closure |
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Download this section (compressed HTML)Q: Should VPS28 ubiquitin binding be retired or qualified because the primary evidence supports TSG101-mediated ubiquitin binding by the TSG101-VPS28 complex rather than direct VPS28 binding?
Suggested experts: GO molecular function editors, UniProt curators
Q: Should broad VPS28 macroautophagy annotations be replaced with GO:0000045 autophagosome assembly to capture ESCRT-I-dependent phagophore closure?
Suggested experts: GO autophagy editors, GO ESCRT curators
Q: Should viral budding, exosome, and plasma-membrane rows remain non-core in proteostasis-focused VPS28 curation?
Suggested experts: GO viral process editors, GO extracellular vesicle editors
Experiment: Use endogenous VPS28 depletion/rescue with wild-type and helical-interface mutants, then measure HT-LC3 closure, ESCRT-I/ESCRT-III recruitment, and EGFR MVB sorting side by side.
Hypothesis: The VPS28 helical interface is required for ESCRT-I accumulation and phagophore closure without abolishing assembly of individual ESCRT-I tetramers.
Type: VPS28 separation-of-function autophagosome closure assay
Experiment: Compare purified VPS28, TSG101, and reconstituted ESCRT-I subcomplexes in quantitative ubiquitin-binding assays with matched positive and negative controls.
Hypothesis: VPS28 does not independently bind ubiquitin; ubiquitin recognition by VPS28-containing ESCRT-I depends on TSG101 or other subunits.
Type: direct ubiquitin-binding assay for purified VPS28
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