Existing Annotations Review

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

Core Functions

VPS28 is a structural/scaffold subunit of ESCRT-I that organizes the TSG101-VPS37-MVB12/UBAP ESCRT-I assembly for endosomal cargo sorting, MVB membrane remodeling, and ESCRT-I-dependent phagophore/autophagosome closure.

Directly Involved In:

ubiquitin-dependent protein catabolic process via the multivesicular body sorting pathway multivesicular body assembly membrane fission autophagosome assembly

Cellular Locations:

endosome membrane late endosome membrane endosome

In Complex:

ESCRT I complex

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
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
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

References

GO_REF:0000002

Gene Ontology annotation through association of InterPro records with GO terms

GO_REF:0000033

Annotation inferences using phylogenetic trees

GO_REF:0000044

Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular Location vocabulary mapping, accompanied by conservative changes to GO terms applied by UniProt

GO_REF:0000107

Automatic transfer of experimentally verified manual GO annotation data to orthologs using Ensembl Compara

GO_REF:0000117

Electronic Gene Ontology annotations created by ARBA machine learning models

GO_REF:0000120

Combined Automated Annotation using Multiple IEA Methods

PMID:11134028

TSG101/mammalian VPS23 and mammalian VPS28 interact directly and are recruited to VPS4-induced endosomes.

PMID:11916981

Mammalian class E vps proteins recognize ubiquitin and act in the removal of endosomal protein-ubiquitin conjugates.

PMID:14505570

The protein network of HIV budding.

PMID:14519844

Divergent retroviral late-budding domains recruit vacuolar protein sorting factors by using alternative adaptor proteins.

PMID:15218037

The human endosomal sorting complex required for transport (ESCRT-I) and its role in HIV-1 budding.

PMID:16189514

Towards a proteome-scale map of the human protein-protein interaction network.

PMID:17940959

Involvement of vacuolar protein sorting pathway in Ebola virus release independent of TSG101 interaction.

PMID:18005716

Identification of human MVB12 proteins as ESCRT-I subunits that function in HIV budding.

PMID:18077552

Regulation of Tsg101 expression by the steadiness box: a role of Tsg101-associated ligase.

PMID:19056867

Large-scale proteomics and phosphoproteomics of urinary exosomes.

PMID:19060904

An empirical framework for binary interactome mapping.

PMID:19199708

Proteomic analysis of human parotid gland exosomes by multidimensional protein identification technology (MudPIT).

PMID:20458337

MHC class II-associated proteins in B-cell exosomes and potential functional implications for exosome biogenesis.

PMID:20588296

Membrane budding and scission by the ESCRT machinery: it's all in the neck.

PMID:20654576

Distinct functions of human MVB12A and MVB12B in the ESCRT-I dependent on their posttranslational modifications.

PMID:21516116

Next-generation sequencing to generate interactome datasets.

PMID:21757351

UBAP1 is a component of an endosome-specific ESCRT-I complex that is essential for MVB sorting.

PMID:22232651

Structural basis for membrane targeting by the MVB12-associated β-prism domain of the human ESCRT-I MVB12 subunit.

PMID:23533145

In-depth proteomic analyses of exosomes isolated from expressed prostatic secretions in urine.

PMID:25416956

A proteome-scale map of the human interactome network.

PMID:25959826

Quantitative interaction proteomics of neurodegenerative disease proteins.

PMID:26871637

Widespread Expansion of Protein Interaction Capabilities by Alternative Splicing.

PMID:28514442

Architecture of the human interactome defines protein communities and disease networks.

PMID:31515488

Extensive disruption of protein interactions by genetic variants across the allele frequency spectrum in human populations.

PMID:32424346

A helical assembly of human ESCRT-I scaffolds reverse-topology membrane scission.

PMID:32814053

Interactome Mapping Provides a Network of Neurodegenerative Disease Proteins and Uncovers Widespread Protein Aggregation in Affected Brains.

PMID:33961781

Dual proteome-scale networks reveal cell-specific remodeling of the human interactome.

PMID:35271311

OpenCell: Endogenous tagging for the cartography of human cellular organization.

Reactome:R-HSA-184269

Monoubiquitinated N-myristoyl GAG polyprotein is targeted to the late endosomal vesicle membrane by the ESCRT-I complex

Reactome:R-HSA-3149434

Transport of GAG to the Plasma Membrane

Reactome:R-HSA-3159232

Recruitment Of HIV Virion Budding Machinery

Reactome:R-HSA-917696

Cargo Sequestration

Reactome:R-HSA-917730

Cargo Recognition And Sorting

PMID:31519728

VPS37A directs ESCRT recruitment for phagophore closure.

file:human/VPS28/VPS28-uniprot.txt

UniProtKB record for human VPS28

file:human/VPS28/VPS28-notes.md

VPS28 review notes

Suggested Experiments

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

📚 Additional Documentation

Notes

(VPS28-notes.md)

VPS28 review notes

Scope

VPS28 is reviewed in the PN autophagophore sealing branch as a core ESCRT-I subunit. PN entries without PMIDs were used as context only. The main curation issue is to separate direct VPS28 function in ESCRT-I assembly and membrane remodeling from complex-level ubiquitin recognition that is mediated mainly by TSG101.

Evidence synthesis

VPS28 is a constitutive ESCRT-I component. UniProt describes VPS28 as a "Component of the ESCRT-I complex" and says the complex "consists of TSG101, VPS28, a VPS37 protein" with MVB12A/MVB12B or UBAP1 variants [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"]. Human ESCRT-I papers similarly state that "All ESCRT-I complexes contain three common subunits (TSG101, VPS28, and VPS37)" and that human ESCRT-I is a heterotetramer of TSG101, Vps28, Vps37, and MVB12 [PMID:18005716, "All ESCRT-I complexes contain three common subunits"; PMID:20654576, "comprises a heterotetramer of TSG101 (Vps23), Vps28, Vps37 and MVB12 protein"]. These sources support accepting ESCRT-I complex membership and core endosomal ESCRT-I sorting annotations.

VPS28 participates in endosomal sorting and MVB-related trafficking as part of ESCRT-I. The original mammalian VPS28 paper states that VPS28 is a "cytosolic protein that interacts with TSG101/mammalian VPS23" and that TSG101/hVPS28 translocate to "the surface of these vacuoles" when dominant-negative VPS4 induces endosomal vacuolization [PMID:11134028, "cytosolic protein that interacts with TSG101/mammalian VPS23"; PMID:11134028, "the surface of these vacuoles"]. The receptor-sorting study reports that the "TSG101 and hVPS28" complex localizes to ubiquitin-rich EGF-positive endosomes and that "antibodies to VPS28 specifically impair EGF degradation" [PMID:11916981, "TSG101 and hVPS28 are localized to ubiquitin-rich endosomes"; PMID:11916981, "antibodies to VPS28 specifically impair EGF degradation"]. These lines support the endosome/endosome membrane, MVB sorting, and ubiquitin-dependent endocytic cargo sorting process rows.

The ubiquitin binding rows should not be accepted as direct VPS28 molecular function. The same paper reports that "Both TSG101 and hVPS28 bound specifically to ubiquitin-agarose" in cytosol, but then shows that "In vitro-translated hVPS28 did not bind to ubiquitin-agarose" and concludes that complex binding occurs through the TSG101 UEV domain [PMID:11916981, "Both TSG101 and hVPS28 bound specifically to ubiquitin-agarose"; PMID:11916981, "In vitro-translated hVPS28 did not bind to ubiquitin-agarose"; PMID:11916981, "complex binding to ubiquitin via the Ubc domain of TSG101"]. This supports marking VPS28 ubiquitin binding as over-annotated rather than core MF.

The PN-specific autophagy connection is now stronger than the older generic macroautophagy row. A phagophore-closure study reports that loss of VPS37A abrogates recruitment of "the ESCRT-I subunit VPS28 and CHMP2A" to phagophores [PMID:31519728, "the ESCRT-I subunit VPS28 and CHMP2A"]. A later ESCRT-I structural paper reports that mutation of VPS28 helical-interface residues blocks ESCRT-I filament formation and "autophagosome closure in cells", and explicitly states that the "ESCRT-I helical interface is required for autophagosome closure" [PMID:32424346, "blocks filament formation in vitro and autophagosome closure"; PMID:32424346, "ESCRT-I helical interface is required for autophagosome closure"]. Therefore the autophagy rows are better represented as GO:0000045 autophagosome assembly than broad macroautophagy.

Generic protein binding rows should be marked over-annotated. Many are from interaction screens or ESCRT subunit interactions, but the informative biology is ESCRT-I complex membership and ESCRT-I-mediated endosomal sorting, not a generic binding MF. Viral budding, extracellular exosome, plasma membrane, cytosol, and cytoplasm rows are true contexts or detection/localization observations but should not be treated as VPS28 core function in this PN review.

Falcon

Falcon deep research was started for VPS28 on 2026-06-02 but timed out after 600 seconds and did not produce a usable report. The review therefore relies on UniProt, cached primary literature, and PN context rather than Falcon output.

Description cleanup note

The YAML description field was revised to keep it as a standalone biological summary. Project-specific curation framing moved here instead.

Moved out of the YAML description: the prior wording described phagophore/autophagosome closure as PN-relevant.

Pn Notes

(VPS28-pn-notes.md)

VPS28 PN Consistency Notes

Generated: 2026-06-18
Project: PROTEOSTASIS
Scope: PN consistency rereview against local AIGR review and available deep-research artifacts
UniProt: Q9UK41
AIGR review status: COMPLETE
Review batch: proteostasis-pr-1217 (PR 1217)
Batch change status: added

Source Files Checked

AIGR review YAML: present - genes/human/VPS28/VPS28-ai-review.yaml
AIGR review HTML: present - genes/human/VPS28/VPS28-ai-review.html
Gene notes: present - genes/human/VPS28/VPS28-notes.md
GOA TSV: present - genes/human/VPS28/VPS28-goa.tsv
UniProt record: present - genes/human/VPS28/VPS28-uniprot.txt
PN dossier: projects/PROTEOSTASIS/reports/phase1_dossiers/VPS28.md
PN consistency section: projects/PROTEOSTASIS/reports/phase1_dossiers/_sections/VPS28.md
PN projection report: projects/PROTEOSTASIS/reports/pn_projection/pn_projected_gene_go_summary.tsv
PN mapping audit: projects/PROTEOSTASIS/reports/pn_mapping_audit/current_mapping_scrutiny.tsv

Deep Research Files

No *-deep-research*.md file found in this gene directory.

AIGR Review Snapshot

Description: 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.
Existing/core annotation action counts: ACCEPT: 31; KEEP_AS_NON_CORE: 12; MARK_AS_OVER_ANNOTATED: 18; MODIFY: 3; NEW: 1

PN Consistency Summary

Consistency: Strong agreement. Deep research/notes, review, and PN all treat VPS28 as a constitutive structural/scaffold ESCRT-I subunit acting in MVB sorting plus ESCRT-I-dependent phagophore/autophagosome closure. The review adds nuance the PN does not contradict: VPS28 itself does not bind ubiquitin (TSG101 UEV does), so it MARKs GO:0043130 over-annotated.
PN story / NEW pressure: ESCRT-I membership (GO:0000813) is already_in_goa. For the autophagy role, GOA only has broad GO:0016236 macroautophagy; the review MODIFYs that to GO:0000045 autophagosome assembly AND adds GO:0000045 as a NEW annotation (IMP, PMID:32424346 helical-interface mutant → closure defect). This matches the PN projection exactly. Verdict: PN story is real and the review correctly adds the more specific GO:0000045 (new to direct GOA).
Evidence alignment: PN cites only PMID:32424346. Review's autophagy evidence pairs PMID:32424346 with PMID:31519728 (VPS37A directs ESCRT recruitment for phagophore closure) and PMID:20588296 — broader and concordant. ESCRT-I/MVB core uses PMID:11134028/11916981/18005716/20654576/21757351. Good overlap, review is richer.
Verdict: Consistent and well-supported; the VPS28 review is the model case for this ESCRT-I leaf — GO:0000045 NEW is justified and matches the PN mapping.

Full Consistency Review

UniProt: Q9UK41 · batch: proteostasis-pr-1217 · review status: COMPLETE
PN placement: ALP …|Sealing of autophagophore membrane|ESCRT-I complex component ; PN-node mapping: leaf mapped/ok_for_propagation GO:0000813 ESCRT I complex (already_in_goa_exact); group mapped GO:0000045 autophagosome assembly (more_specific_than_existing_goa).
Consistency: Strong agreement. Deep research/notes, review, and PN all treat VPS28 as a constitutive structural/scaffold ESCRT-I subunit acting in MVB sorting plus ESCRT-I-dependent phagophore/autophagosome closure. The review adds nuance the PN does not contradict: VPS28 itself does not bind ubiquitin (TSG101 UEV does), so it MARKs GO:0043130 over-annotated.
PN story / NEW pressure: ESCRT-I membership (GO:0000813) is already_in_goa. For the autophagy role, GOA only has broad GO:0016236 macroautophagy; the review MODIFYs that to GO:0000045 autophagosome assembly AND adds GO:0000045 as a NEW annotation (IMP, PMID:32424346 helical-interface mutant → closure defect). This matches the PN projection exactly. Verdict: PN story is real and the review correctly adds the more specific GO:0000045 (new to direct GOA).
Mapping strategy: VPS28 legitimately supports the ALP leaf (GO:0000813) and group (GO:0000045) projections — unlike UBAP1/UMAD1 it has direct VPS28 closure evidence (PMID:31519728, PMID:32424346). Scope ok_for_propagation is justified; PN-projected GO:0000045 is appropriately narrower than parent macroautophagy and aligns with the review.
Evidence alignment: PN cites only PMID:32424346. Review's autophagy evidence pairs PMID:32424346 with PMID:31519728 (VPS37A directs ESCRT recruitment for phagophore closure) and PMID:20588296 — broader and concordant. ESCRT-I/MVB core uses PMID:11134028/11916981/18005716/20654576/21757351. Good overlap, review is richer.
Verdict: Consistent and well-supported; the VPS28 review is the model case for this ESCRT-I leaf — GO:0000045 NEW is justified and matches the PN mapping.

PN Dossier Context

review_batch: proteostasis-pr-1217
review_yaml: genes/human/VPS28/VPS28-ai-review.yaml
PN workbook rows: 1

PN row 1: Autophagy-Lysosome Pathway | Autophagosome closure maturation and lysosome fusion | Sealing of autophagophore membrane | ESCRT-I complex component

UniProt: Q9UK41
In branches: ALP
Notes: Component of the ESCRT-I complex, involved in autophagosome closure
PN references (titles):
- A helical assembly of human ESCRT-I scaffolds reverse-topology membrane scission | Nature Structural & Molecular Biology
PN-node mapping records (path + ancestors):
- [type] Autophagy-Lysosome Pathway|Autophagosome closure maturation and lysosome fusion|Sealing of autophagophore membrane|ESCRT-I complex component
  status=mapped scope=ok_for_propagation_to_go GO=[GO:0000813 ESCRT I complex]
  rationale: This leaf is restricted to ESCRT-I components used in autophagophore sealing. The shared GO assertion is ESCRT I complex membership.
- [group] Autophagy-Lysosome Pathway|Autophagosome closure maturation and lysosome fusion|Sealing of autophagophore membrane
  status=mapped scope=ok_for_propagation_to_go GO=[GO:0000045 autophagosome assembly]
  rationale: This group captures autophagophore closure/sealing, a late step in autophagosome assembly. Autophagosome assembly is the safer process target than autophagosome-lysosome fusion.
- [class] Autophagy-Lysosome Pathway|Autophagosome closure maturation and lysosome fusion
  status=context_only scope=too_broad_to_propagate GO=[GO:0016236 macroautophagy]
  rationale: This class is a late macroautophagy context, but the subtree mixes docking, fusion, localization, membrane-composition, and unknown late-stage roles. The class-level relation is useful for display while propagation is restricted to narrower mechanism nodes.
- [branch] Autophagy-Lysosome Pathway
  status=no_mapping scope= GO=[]
  rationale: Reviewed as the top-level PN branch. It is a project taxonomy umbrella rather than a direct GO assertion; all propagation must come from manually curated child nodes.

Projected GO annotations (2)

GO:0000045 autophagosome assembly | scope=ok_for_propagation_to_go | goa_status=more_specific_than_existing_goa | from=Autophagy-Lysosome Pathway|Autophagosome closure maturation and lysosome fusion|Sealing of autophagophore membrane
GO:0000813 ESCRT I complex | scope=ok_for_propagation_to_go | goa_status=already_in_goa_exact | from=Autophagy-Lysosome Pathway|Autophagosome closure maturation and lysosome fusion|Sealing of autophagophore membrane|ESCRT-I complex component

Note

This file is generated from the current PROTEOSTASIS phase-1 dossier and local gene-review artifacts. Edit the source review, PN mapping, or dossier rather than this generated note when correcting the underlying curation.

📄 View Raw YAML

id: Q9UK41
gene_symbol: VPS28
product_type: PROTEIN
status: COMPLETE
taxon:
  id: NCBITaxon:9606
  label: Homo sapiens
description: >-
  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.
alternative_products:
- name: '1'
  id: Q9UK41-1
- name: '2'
  id: Q9UK41-2
  sequence_note: VSP_042028
existing_annotations:
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: is_active_in
  review:
    summary: cytosol localization is supported but broad and non-core.
    action: KEEP_AS_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.
    additional_reference_ids: &id018
    - PMID:11134028
    - file:human/VPS28/VPS28-uniprot.txt
    - file:human/VPS28/VPS28-notes.md
    supported_by: &id019
    - reference_id: PMID:11134028
      supporting_text: cytosolic protein that interacts with TSG101/mammalian VPS23
    - reference_id: PMID:11134028
      supporting_text: TSG101 and hVPS28 are predominantly cytosolic
- term:
    id: GO:0043130
    label: ubiquitin binding
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: enables
  review:
    summary: Direct ubiquitin binding is over-annotated for VPS28.
    action: MARK_AS_OVER_ANNOTATED
    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_replacement_terms: &id025
    - 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: &id026
    - PMID:11916981
    - file:human/VPS28/VPS28-uniprot.txt
    - file:human/VPS28/VPS28-notes.md
    supported_by: &id027
    - reference_id: PMID:11916981
      supporting_text: Both TSG101 and hVPS28 bound specifically to ubiquitin-agarose
    - reference_id: PMID:11916981
      supporting_text: hVPS28 did not bind to ubiquitin-agarose
    - reference_id: PMID:11916981
      supporting_text: complex binding to ubiquitin via the Ubc domain of TSG101
- 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 VPS28 cellular-component annotation.
    action: ACCEPT
    reason: VPS28 is a constitutive ESCRT-I subunit in TSG101-VPS28-VPS37-MVB12/UBAP variant complexes.
    additional_reference_ids: &id001
    - PMID:18005716
    - PMID:20654576
    - file:human/VPS28/VPS28-uniprot.txt
    - file:human/VPS28/VPS28-notes.md
    supported_by: &id002
    - &id007
      reference_id: file:human/VPS28/VPS28-uniprot.txt
      supporting_text: Component of the ESCRT-I complex
    - &id008
      reference_id: file:human/VPS28/VPS28-uniprot.txt
      supporting_text: which consists of TSG101, VPS28, a VPS37
    - &id009
      reference_id: PMID:18005716
      supporting_text: All ESCRT-I complexes contain three
    - &id010
      reference_id: PMID:18005716
      supporting_text: TSG101, VPS28, and VPS37
    - &id011
      reference_id: PMID:20654576
      supporting_text: comprises a heterotetramer of TSG101
- term:
    id: GO:0043328
    label: protein transport to vacuole involved in 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: 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.
    action: ACCEPT
    reason: VPS28/ESCRT-I supports ubiquitin-dependent endosomal receptor/cargo sorting into MVBs and delivery
      toward lysosomal degradation.
    additional_reference_ids: &id003
    - PMID:11134028
    - PMID:11916981
    - PMID:21757351
    - file:human/VPS28/VPS28-uniprot.txt
    - file:human/VPS28/VPS28-notes.md
    supported_by: &id004
    - &id012
      reference_id: PMID:11134028
      supporting_text: directly involved in endosomal sorting
    - &id013
      reference_id: PMID:11916981
      supporting_text: TSG101 and VPS28 are localized to ubiquitin-rich endosomes
    - &id014
      reference_id: PMID:11916981
      supporting_text: antibodies to VPS28 specifically impair EGF degradation
    - &id015
      reference_id: PMID:21757351
      supporting_text: required for sorting EGFR to the MVB
    - &id016
      reference_id: file:human/VPS28/VPS28-uniprot.txt
      supporting_text: Component of the ESCRT-I complex, a regulator of vesicular
- term:
    id: GO:0000813
    label: ESCRT I complex
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  qualifier: part_of
  review:
    summary: ESCRT-I complex membership is the central VPS28 cellular-component annotation.
    action: ACCEPT
    reason: VPS28 is a constitutive ESCRT-I subunit in TSG101-VPS28-VPS37-MVB12/UBAP variant complexes.
    additional_reference_ids: *id001
    supported_by: *id002
- term:
    id: GO:0005886
    label: plasma membrane
  evidence_type: IEA
  original_reference_id: GO_REF:0000044
  qualifier: located_in
  review:
    summary: plasma membrane is supported as a context but is not the core VPS28 proteostasis function.
    action: KEEP_AS_NON_CORE
    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.
    additional_reference_ids: &id005
    - PMID:18005716
    - PMID:20588296
    - PMID:32424346
    - file:human/VPS28/VPS28-uniprot.txt
    - file:human/VPS28/VPS28-notes.md
    supported_by: &id006
    - reference_id: PMID:18005716
      supporting_text: plays essential roles in HIV budding and endosomal protein sorting
    - reference_id: PMID:20588296
      supporting_text: viral budding, cytokinesis and, probably, autophagy
    - reference_id: file:human/VPS28/VPS28-uniprot.txt
      supporting_text: Cell membrane
- term:
    id: GO:0016236
    label: macroautophagy
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  qualifier: involved_in
  review:
    summary: Macroautophagy is too broad for the VPS28 ESCRT-I autophagy role.
    action: MODIFY
    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_replacement_terms: &id022
    - id: GO:0000045
      label: autophagosome assembly
    additional_reference_ids: &id023
    - PMID:31519728
    - PMID:32424346
    - file:human/VPS28/VPS28-notes.md
    supported_by: &id024
    - &id031
      reference_id: PMID:31519728
      supporting_text: ESCRT-I subunit VPS28 and CHMP2A
    - &id032
      reference_id: PMID:31519728
      supporting_text: phagophore closure in mammalian cells
    - &id033
      reference_id: PMID:32424346
      supporting_text: ESCRT-I helical interface is required for autophagosome closure
    - &id034
      reference_id: PMID:32424346
      supporting_text: blocks filament formation in vitro and autophagosome closure
- 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 VPS28/ESCRT-I function.
    action: ACCEPT
    reason: VPS28 is a soluble ESCRT-I component that is recruited to endosomal membranes during cargo sorting
      and MVB-related ESCRT activity.
    additional_reference_ids: &id020
    - PMID:11134028
    - PMID:11916981
    - file:human/VPS28/VPS28-uniprot.txt
    - file:human/VPS28/VPS28-notes.md
    supported_by: &id021
    - reference_id: PMID:11134028
      supporting_text: TSG101 and hVPS28 are predominantly cytosolic
    - reference_id: PMID:11134028
      supporting_text: translocated to the surface of these vacuoles
    - reference_id: PMID:11916981
      supporting_text: TSG101 and VPS28 are localized to ubiquitin-rich endosomes
    - reference_id: file:human/VPS28/VPS28-uniprot.txt
      supporting_text: "Late\nCC       endosome membrane"
- term:
    id: GO:0032509
    label: endosome transport via multivesicular body sorting pathway
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  qualifier: involved_in
  review:
    summary: endosome transport via multivesicular body sorting pathway is supported as part of the core
      ESCRT-I endosomal cargo-sorting role.
    action: ACCEPT
    reason: VPS28/ESCRT-I supports ubiquitin-dependent endosomal receptor/cargo sorting into MVBs and delivery
      toward lysosomal degradation.
    additional_reference_ids: *id003
    supported_by: *id004
- term:
    id: GO:0036258
    label: multivesicular body assembly
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  qualifier: involved_in
  review:
    summary: multivesicular body assembly is supported as part of the core ESCRT-I endosomal cargo-sorting
      role.
    action: ACCEPT
    reason: VPS28/ESCRT-I supports ubiquitin-dependent endosomal receptor/cargo sorting into MVBs and delivery
      toward lysosomal degradation.
    additional_reference_ids: *id003
    supported_by: *id004
- term:
    id: GO:0039702
    label: viral budding via host ESCRT complex
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  qualifier: involved_in
  review:
    summary: viral budding via host ESCRT complex is supported as a context but is not the core VPS28
      proteostasis function.
    action: KEEP_AS_NON_CORE
    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.
    additional_reference_ids: *id005
    supported_by: *id006
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:16189514
  qualifier: enables
  review:
    summary: Protein binding is too generic to represent VPS28 function.
    action: MARK_AS_OVER_ANNOTATED
    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_replacement_terms: &id017
    - id: GO:0000813
      label: ESCRT I complex
    - id: GO:0036258
      label: multivesicular body assembly
    additional_reference_ids:
    - PMID:18005716
    - PMID:20654576
    - file:human/VPS28/VPS28-uniprot.txt
    - file:human/VPS28/VPS28-notes.md
    - PMID:11134028
    - PMID:11916981
    - PMID:21757351
    - file:human/VPS28/VPS28-uniprot.txt
    - file:human/VPS28/VPS28-notes.md
    supported_by:
    - *id007
    - *id008
    - *id009
    - *id010
    - *id011
    - *id012
    - *id013
    - *id014
    - *id015
    - *id016
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:19060904
  qualifier: enables
  review:
    summary: Protein binding is too generic to represent VPS28 function.
    action: MARK_AS_OVER_ANNOTATED
    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_replacement_terms: *id017
    additional_reference_ids:
    - PMID:18005716
    - PMID:20654576
    - file:human/VPS28/VPS28-uniprot.txt
    - file:human/VPS28/VPS28-notes.md
    - PMID:11134028
    - PMID:11916981
    - PMID:21757351
    - file:human/VPS28/VPS28-uniprot.txt
    - file:human/VPS28/VPS28-notes.md
    supported_by:
    - *id007
    - *id008
    - *id009
    - *id010
    - *id011
    - *id012
    - *id013
    - *id014
    - *id015
    - *id016
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:21516116
  qualifier: enables
  review:
    summary: Protein binding is too generic to represent VPS28 function.
    action: MARK_AS_OVER_ANNOTATED
    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_replacement_terms: *id017
    additional_reference_ids:
    - PMID:18005716
    - PMID:20654576
    - file:human/VPS28/VPS28-uniprot.txt
    - file:human/VPS28/VPS28-notes.md
    - PMID:11134028
    - PMID:11916981
    - PMID:21757351
    - file:human/VPS28/VPS28-uniprot.txt
    - file:human/VPS28/VPS28-notes.md
    supported_by:
    - *id007
    - *id008
    - *id009
    - *id010
    - *id011
    - *id012
    - *id013
    - *id014
    - *id015
    - *id016
- 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 VPS28 function.
    action: MARK_AS_OVER_ANNOTATED
    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_replacement_terms: *id017
    additional_reference_ids:
    - PMID:18005716
    - PMID:20654576
    - file:human/VPS28/VPS28-uniprot.txt
    - file:human/VPS28/VPS28-notes.md
    - PMID:11134028
    - PMID:11916981
    - PMID:21757351
    - file:human/VPS28/VPS28-uniprot.txt
    - file:human/VPS28/VPS28-notes.md
    supported_by:
    - *id007
    - *id008
    - *id009
    - *id010
    - *id011
    - *id012
    - *id013
    - *id014
    - *id015
    - *id016
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:25959826
  qualifier: enables
  review:
    summary: Protein binding is too generic to represent VPS28 function.
    action: MARK_AS_OVER_ANNOTATED
    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_replacement_terms: *id017
    additional_reference_ids:
    - PMID:18005716
    - PMID:20654576
    - file:human/VPS28/VPS28-uniprot.txt
    - file:human/VPS28/VPS28-notes.md
    - PMID:11134028
    - PMID:11916981
    - PMID:21757351
    - file:human/VPS28/VPS28-uniprot.txt
    - file:human/VPS28/VPS28-notes.md
    supported_by:
    - *id007
    - *id008
    - *id009
    - *id010
    - *id011
    - *id012
    - *id013
    - *id014
    - *id015
    - *id016
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:26871637
  qualifier: enables
  review:
    summary: Protein binding is too generic to represent VPS28 function.
    action: MARK_AS_OVER_ANNOTATED
    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_replacement_terms: *id017
    additional_reference_ids:
    - PMID:18005716
    - PMID:20654576
    - file:human/VPS28/VPS28-uniprot.txt
    - file:human/VPS28/VPS28-notes.md
    - PMID:11134028
    - PMID:11916981
    - PMID:21757351
    - file:human/VPS28/VPS28-uniprot.txt
    - file:human/VPS28/VPS28-notes.md
    supported_by:
    - *id007
    - *id008
    - *id009
    - *id010
    - *id011
    - *id012
    - *id013
    - *id014
    - *id015
    - *id016
- 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 VPS28 function.
    action: MARK_AS_OVER_ANNOTATED
    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_replacement_terms: *id017
    additional_reference_ids:
    - PMID:18005716
    - PMID:20654576
    - file:human/VPS28/VPS28-uniprot.txt
    - file:human/VPS28/VPS28-notes.md
    - PMID:11134028
    - PMID:11916981
    - PMID:21757351
    - file:human/VPS28/VPS28-uniprot.txt
    - file:human/VPS28/VPS28-notes.md
    supported_by:
    - *id007
    - *id008
    - *id009
    - *id010
    - *id011
    - *id012
    - *id013
    - *id014
    - *id015
    - *id016
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:31515488
  qualifier: enables
  review:
    summary: Protein binding is too generic to represent VPS28 function.
    action: MARK_AS_OVER_ANNOTATED
    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_replacement_terms: *id017
    additional_reference_ids:
    - PMID:18005716
    - PMID:20654576
    - file:human/VPS28/VPS28-uniprot.txt
    - file:human/VPS28/VPS28-notes.md
    - PMID:11134028
    - PMID:11916981
    - PMID:21757351
    - file:human/VPS28/VPS28-uniprot.txt
    - file:human/VPS28/VPS28-notes.md
    supported_by:
    - *id007
    - *id008
    - *id009
    - *id010
    - *id011
    - *id012
    - *id013
    - *id014
    - *id015
    - *id016
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:32814053
  qualifier: enables
  review:
    summary: Protein binding is too generic to represent VPS28 function.
    action: MARK_AS_OVER_ANNOTATED
    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_replacement_terms: *id017
    additional_reference_ids:
    - PMID:18005716
    - PMID:20654576
    - file:human/VPS28/VPS28-uniprot.txt
    - file:human/VPS28/VPS28-notes.md
    - PMID:11134028
    - PMID:11916981
    - PMID:21757351
    - file:human/VPS28/VPS28-uniprot.txt
    - file:human/VPS28/VPS28-notes.md
    supported_by:
    - *id007
    - *id008
    - *id009
    - *id010
    - *id011
    - *id012
    - *id013
    - *id014
    - *id015
    - *id016
- 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 VPS28 function.
    action: MARK_AS_OVER_ANNOTATED
    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_replacement_terms: *id017
    additional_reference_ids:
    - PMID:18005716
    - PMID:20654576
    - file:human/VPS28/VPS28-uniprot.txt
    - file:human/VPS28/VPS28-notes.md
    - PMID:11134028
    - PMID:11916981
    - PMID:21757351
    - file:human/VPS28/VPS28-uniprot.txt
    - file:human/VPS28/VPS28-notes.md
    supported_by:
    - *id007
    - *id008
    - *id009
    - *id010
    - *id011
    - *id012
    - *id013
    - *id014
    - *id015
    - *id016
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:35271311
  qualifier: enables
  review:
    summary: Protein binding is too generic to represent VPS28 function.
    action: MARK_AS_OVER_ANNOTATED
    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_replacement_terms: *id017
    additional_reference_ids:
    - PMID:18005716
    - PMID:20654576
    - file:human/VPS28/VPS28-uniprot.txt
    - file:human/VPS28/VPS28-notes.md
    - PMID:11134028
    - PMID:11916981
    - PMID:21757351
    - file:human/VPS28/VPS28-uniprot.txt
    - file:human/VPS28/VPS28-notes.md
    supported_by:
    - *id007
    - *id008
    - *id009
    - *id010
    - *id011
    - *id012
    - *id013
    - *id014
    - *id015
    - *id016
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: located_in
  review:
    summary: cytosol localization is supported but broad and non-core.
    action: KEEP_AS_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.
    additional_reference_ids: *id018
    supported_by: *id019
- term:
    id: GO:0000813
    label: ESCRT I complex
  evidence_type: IPI
  original_reference_id: PMID:18005716
  qualifier: part_of
  review:
    summary: ESCRT-I complex membership is the central VPS28 cellular-component annotation.
    action: ACCEPT
    reason: VPS28 is a constitutive ESCRT-I subunit in TSG101-VPS28-VPS37-MVB12/UBAP variant complexes.
    additional_reference_ids: *id001
    supported_by: *id002
- 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 the central VPS28 cellular-component annotation.
    action: ACCEPT
    reason: VPS28 is a constitutive ESCRT-I subunit in TSG101-VPS28-VPS37-MVB12/UBAP variant complexes.
    additional_reference_ids: *id001
    supported_by: *id002
- term:
    id: GO:0000813
    label: ESCRT I complex
  evidence_type: IPI
  original_reference_id: PMID:32424346
  qualifier: part_of
  review:
    summary: ESCRT-I complex membership is the central VPS28 cellular-component annotation.
    action: ACCEPT
    reason: VPS28 is a constitutive ESCRT-I subunit in TSG101-VPS28-VPS37-MVB12/UBAP variant 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 VPS28/ESCRT-I function.
    action: ACCEPT
    reason: VPS28 is a soluble ESCRT-I component that is recruited to endosomal membranes during cargo sorting
      and MVB-related ESCRT activity.
    additional_reference_ids: *id020
    supported_by: *id021
- 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 part of the core ESCRT-I endosomal cargo-sorting
      role.
    action: ACCEPT
    reason: VPS28/ESCRT-I supports ubiquitin-dependent endosomal receptor/cargo sorting into MVBs and delivery
      toward lysosomal degradation.
    additional_reference_ids: *id003
    supported_by: *id004
- 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 part of the core ESCRT-I endosomal cargo-sorting
      role.
    action: ACCEPT
    reason: VPS28/ESCRT-I supports ubiquitin-dependent endosomal receptor/cargo sorting into MVBs and delivery
      toward lysosomal degradation.
    additional_reference_ids: *id003
    supported_by: *id004
- term:
    id: GO:0090148
    label: membrane fission
  evidence_type: NAS
  original_reference_id: PMID:32424346
  qualifier: involved_in
  review:
    summary: Membrane fission is supported for ESCRT-I reverse-topology membrane remodeling.
    action: ACCEPT
    reason: ESCRT-I scaffolds reverse-topology membrane remodeling; VPS28 helical-interface mutations disrupt
      ESCRT-I filament assembly and ESCRT-dependent sealing contexts.
    additional_reference_ids:
    - PMID:20588296
    - PMID:32424346
    - file:human/VPS28/VPS28-notes.md
    supported_by:
    - &id028
      reference_id: PMID:20588296
      supporting_text: ESCRT-I and ESCRT-II direct membrane budding away from the cytosol
    - &id029
      reference_id: PMID:32424346
      supporting_text: A helical assembly of human ESCRT-I scaffolds reverse-topology membrane scission
    - &id030
      reference_id: PMID:32424346
      supporting_text: VPS28 helical interface residues blocks filament formation in vitro and autophagosome
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:15218037
  qualifier: enables
  review:
    summary: Protein binding is too generic to represent VPS28 function.
    action: MARK_AS_OVER_ANNOTATED
    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_replacement_terms: *id017
    additional_reference_ids:
    - PMID:18005716
    - PMID:20654576
    - file:human/VPS28/VPS28-uniprot.txt
    - file:human/VPS28/VPS28-notes.md
    - PMID:11134028
    - PMID:11916981
    - PMID:21757351
    - file:human/VPS28/VPS28-uniprot.txt
    - file:human/VPS28/VPS28-notes.md
    supported_by:
    - *id007
    - *id008
    - *id009
    - *id010
    - *id011
    - *id012
    - *id013
    - *id014
    - *id015
    - *id016
- term:
    id: GO:0016236
    label: macroautophagy
  evidence_type: TAS
  original_reference_id: PMID:20588296
  qualifier: involved_in
  review:
    summary: Macroautophagy is too broad for the VPS28 ESCRT-I autophagy role.
    action: MODIFY
    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_replacement_terms: *id022
    additional_reference_ids: *id023
    supported_by: *id024
- term:
    id: GO:0000813
    label: ESCRT I complex
  evidence_type: TAS
  original_reference_id: PMID:20588296
  qualifier: part_of
  review:
    summary: ESCRT-I complex membership is the central VPS28 cellular-component annotation.
    action: ACCEPT
    reason: VPS28 is a constitutive ESCRT-I subunit in TSG101-VPS28-VPS37-MVB12/UBAP variant complexes.
    additional_reference_ids: *id001
    supported_by: *id002
- term:
    id: GO:0036258
    label: multivesicular body assembly
  evidence_type: TAS
  original_reference_id: PMID:20588296
  qualifier: involved_in
  review:
    summary: multivesicular body assembly is supported as part of the core ESCRT-I endosomal cargo-sorting
      role.
    action: ACCEPT
    reason: VPS28/ESCRT-I supports ubiquitin-dependent endosomal receptor/cargo sorting into MVBs and delivery
      toward lysosomal degradation.
    additional_reference_ids: *id003
    supported_by: *id004
- term:
    id: GO:0039702
    label: viral budding via host ESCRT complex
  evidence_type: TAS
  original_reference_id: PMID:20588296
  qualifier: involved_in
  review:
    summary: viral budding via host ESCRT complex is supported as a context but is not the core VPS28
      proteostasis function.
    action: KEEP_AS_NON_CORE
    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.
    additional_reference_ids: *id005
    supported_by: *id006
- 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 VPS28 cellular-component annotation.
    action: ACCEPT
    reason: VPS28 is a constitutive ESCRT-I subunit in TSG101-VPS28-VPS37-MVB12/UBAP variant complexes.
    additional_reference_ids: *id001
    supported_by: *id002
- term:
    id: GO:0005768
    label: endosome
  evidence_type: IDA
  original_reference_id: PMID:17940959
  qualifier: located_in
  review:
    summary: endosome localization is supported and relevant to VPS28/ESCRT-I function.
    action: ACCEPT
    reason: VPS28 is a soluble ESCRT-I component that is recruited to endosomal membranes during cargo sorting
      and MVB-related ESCRT activity.
    additional_reference_ids: *id020
    supported_by: *id021
- term:
    id: GO:0005886
    label: plasma membrane
  evidence_type: IDA
  original_reference_id: PMID:17940959
  qualifier: located_in
  review:
    summary: plasma membrane is supported as a context but is not the core VPS28 proteostasis function.
    action: KEEP_AS_NON_CORE
    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.
    additional_reference_ids: *id005
    supported_by: *id006
- term:
    id: GO:0045732
    label: positive regulation of protein catabolic process
  evidence_type: IMP
  original_reference_id: PMID:11916981
  qualifier: involved_in
  review:
    summary: Positive regulation of protein catabolic process is too broad for the VPS28 evidence.
    action: MODIFY
    reason: The PMID:11916981 evidence specifically concerns EGF/EGFR degradation through ubiquitin-dependent
      endosomal sorting rather than a general protein-catabolic regulatory function.
    proposed_replacement_terms:
    - id: GO:2000397
      label: positive regulation of ubiquitin-dependent endocytosis
    - id: GO:0043162
      label: ubiquitin-dependent protein catabolic process via the multivesicular body sorting pathway
    additional_reference_ids: *id003
    supported_by: *id004
- term:
    id: GO:2000397
    label: positive regulation of ubiquitin-dependent endocytosis
  evidence_type: IMP
  original_reference_id: PMID:11916981
  qualifier: involved_in
  review:
    summary: positive regulation of ubiquitin-dependent endocytosis is supported as part of the core ESCRT-I
      endosomal cargo-sorting role.
    action: ACCEPT
    reason: VPS28/ESCRT-I supports ubiquitin-dependent endosomal receptor/cargo sorting into MVBs and delivery
      toward lysosomal degradation.
    additional_reference_ids: *id003
    supported_by: *id004
- term:
    id: GO:0005769
    label: early endosome
  evidence_type: IDA
  original_reference_id: PMID:11916981
  qualifier: located_in
  review:
    summary: early endosome localization is supported and relevant to VPS28/ESCRT-I function.
    action: ACCEPT
    reason: VPS28 is a soluble ESCRT-I component that is recruited to endosomal membranes during cargo sorting
      and MVB-related ESCRT activity.
    additional_reference_ids: *id020
    supported_by: *id021
- term:
    id: GO:0043130
    label: ubiquitin binding
  evidence_type: IDA
  original_reference_id: PMID:11916981
  qualifier: enables
  review:
    summary: Direct ubiquitin binding is over-annotated for VPS28.
    action: MARK_AS_OVER_ANNOTATED
    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_replacement_terms: *id025
    additional_reference_ids: *id026
    supported_by: *id027
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:11134028
  qualifier: enables
  review:
    summary: Protein binding is too generic to represent VPS28 function.
    action: MARK_AS_OVER_ANNOTATED
    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_replacement_terms: *id017
    additional_reference_ids:
    - PMID:18005716
    - PMID:20654576
    - file:human/VPS28/VPS28-uniprot.txt
    - file:human/VPS28/VPS28-notes.md
    - PMID:11134028
    - PMID:11916981
    - PMID:21757351
    - file:human/VPS28/VPS28-uniprot.txt
    - file:human/VPS28/VPS28-notes.md
    supported_by:
    - *id007
    - *id008
    - *id009
    - *id010
    - *id011
    - *id012
    - *id013
    - *id014
    - *id015
    - *id016
- term:
    id: GO:0010008
    label: endosome membrane
  evidence_type: IDA
  original_reference_id: PMID:11134028
  qualifier: located_in
  review:
    summary: endosome membrane localization is supported and relevant to VPS28/ESCRT-I function.
    action: ACCEPT
    reason: VPS28 is a soluble ESCRT-I component that is recruited to endosomal membranes during cargo sorting
      and MVB-related ESCRT activity.
    additional_reference_ids: *id020
    supported_by: *id021
- term:
    id: GO:0070062
    label: extracellular exosome
  evidence_type: HDA
  original_reference_id: PMID:23533145
  qualifier: located_in
  review:
    summary: extracellular exosome is supported as a context but is not the core VPS28 proteostasis function.
    action: KEEP_AS_NON_CORE
    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.
    additional_reference_ids: *id005
    supported_by: *id006
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:14519844
  qualifier: enables
  review:
    summary: Protein binding is too generic to represent VPS28 function.
    action: MARK_AS_OVER_ANNOTATED
    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_replacement_terms: *id017
    additional_reference_ids:
    - PMID:18005716
    - PMID:20654576
    - file:human/VPS28/VPS28-uniprot.txt
    - file:human/VPS28/VPS28-notes.md
    - PMID:11134028
    - PMID:11916981
    - PMID:21757351
    - file:human/VPS28/VPS28-uniprot.txt
    - file:human/VPS28/VPS28-notes.md
    supported_by:
    - *id007
    - *id008
    - *id009
    - *id010
    - *id011
    - *id012
    - *id013
    - *id014
    - *id015
    - *id016
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:14505570
  qualifier: enables
  review:
    summary: Protein binding is too generic to represent VPS28 function.
    action: MARK_AS_OVER_ANNOTATED
    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_replacement_terms: *id017
    additional_reference_ids:
    - PMID:18005716
    - PMID:20654576
    - file:human/VPS28/VPS28-uniprot.txt
    - file:human/VPS28/VPS28-notes.md
    - PMID:11134028
    - PMID:11916981
    - PMID:21757351
    - file:human/VPS28/VPS28-uniprot.txt
    - file:human/VPS28/VPS28-notes.md
    supported_by:
    - *id007
    - *id008
    - *id009
    - *id010
    - *id011
    - *id012
    - *id013
    - *id014
    - *id015
    - *id016
- 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 VPS28 cellular-component annotation.
    action: ACCEPT
    reason: VPS28 is a constitutive ESCRT-I subunit in TSG101-VPS28-VPS37-MVB12/UBAP variant complexes.
    additional_reference_ids: *id001
    supported_by: *id002
- term:
    id: GO:0000813
    label: ESCRT I complex
  evidence_type: IDA
  original_reference_id: PMID:22232651
  qualifier: part_of
  review:
    summary: ESCRT-I complex membership is the central VPS28 cellular-component annotation.
    action: ACCEPT
    reason: VPS28 is a constitutive ESCRT-I subunit in TSG101-VPS28-VPS37-MVB12/UBAP variant complexes.
    additional_reference_ids: *id001
    supported_by: *id002
- 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 the core ESCRT-I endosomal cargo-sorting role.
    action: ACCEPT
    reason: VPS28/ESCRT-I supports ubiquitin-dependent endosomal receptor/cargo sorting into MVBs and delivery
      toward lysosomal degradation.
    additional_reference_ids: *id003
    supported_by: *id004
- term:
    id: GO:0070062
    label: extracellular exosome
  evidence_type: HDA
  original_reference_id: PMID:19199708
  qualifier: located_in
  review:
    summary: extracellular exosome is supported as a context but is not the core VPS28 proteostasis function.
    action: KEEP_AS_NON_CORE
    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.
    additional_reference_ids: *id005
    supported_by: *id006
- 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 context but is not the core VPS28 proteostasis function.
    action: KEEP_AS_NON_CORE
    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.
    additional_reference_ids: *id005
    supported_by: *id006
- term:
    id: GO:0070062
    label: extracellular exosome
  evidence_type: HDA
  original_reference_id: PMID:20458337
  qualifier: located_in
  review:
    summary: extracellular exosome is supported as a context but is not the core VPS28 proteostasis function.
    action: KEEP_AS_NON_CORE
    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.
    additional_reference_ids: *id005
    supported_by: *id006
- 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 the central VPS28 cellular-component annotation.
    action: ACCEPT
    reason: VPS28 is a constitutive ESCRT-I subunit in TSG101-VPS28-VPS37-MVB12/UBAP variant complexes.
    additional_reference_ids: *id001
    supported_by: *id002
- 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 part of the core ESCRT-I endosomal cargo-sorting role.
    action: ACCEPT
    reason: VPS28/ESCRT-I supports ubiquitin-dependent endosomal receptor/cargo sorting into MVBs and delivery
      toward lysosomal degradation.
    additional_reference_ids: *id003
    supported_by: *id004
- 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 VPS28/ESCRT-I function.
    action: ACCEPT
    reason: VPS28 is a soluble ESCRT-I component that is recruited to endosomal membranes during cargo sorting
      and MVB-related ESCRT activity.
    additional_reference_ids: *id020
    supported_by: *id021
- 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 VPS28/ESCRT-I function.
    action: ACCEPT
    reason: VPS28 is a soluble ESCRT-I component that is recruited to endosomal membranes during cargo sorting
      and MVB-related ESCRT activity.
    additional_reference_ids: *id020
    supported_by: *id021
- 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 VPS28/ESCRT-I function.
    action: ACCEPT
    reason: VPS28 is a soluble ESCRT-I component that is recruited to endosomal membranes during cargo sorting
      and MVB-related ESCRT activity.
    additional_reference_ids: *id020
    supported_by: *id021
- 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 VPS28/ESCRT-I function.
    action: ACCEPT
    reason: VPS28 is a soluble ESCRT-I component that is recruited to endosomal membranes during cargo sorting
      and MVB-related ESCRT activity.
    additional_reference_ids: *id020
    supported_by: *id021
- 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 VPS28/ESCRT-I function.
    action: ACCEPT
    reason: VPS28 is a soluble ESCRT-I component that is recruited to endosomal membranes during cargo sorting
      and MVB-related ESCRT activity.
    additional_reference_ids: *id020
    supported_by: *id021
- term:
    id: GO:0005737
    label: cytoplasm
  evidence_type: IDA
  original_reference_id: PMID:18077552
  qualifier: located_in
  review:
    summary: cytoplasm localization is supported but broad and non-core.
    action: KEEP_AS_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.
    additional_reference_ids: *id018
    supported_by: *id019
- term:
    id: GO:0031397
    label: negative regulation of protein ubiquitination
  evidence_type: IDA
  original_reference_id: PMID:18077552
  qualifier: involved_in
  review:
    summary: Negative regulation of protein ubiquitination is a broad over-annotation for VPS28.
    action: MARK_AS_OVER_ANNOTATED
    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_replacement_terms:
    - id: GO:0000813
      label: ESCRT I complex
    additional_reference_ids:
    - PMID:18077552
    - file:human/VPS28/VPS28-notes.md
    supported_by:
    - reference_id: PMID:18077552
      supporting_text: VPS28 is a limiting factor
    - reference_id: PMID:18077552
      supporting_text: presence of the other ESCRT-I proteins
- term:
    id: GO:0005768
    label: endosome
  evidence_type: IDA
  original_reference_id: PMID:11134028
  qualifier: located_in
  review:
    summary: endosome localization is supported and relevant to VPS28/ESCRT-I function.
    action: ACCEPT
    reason: VPS28 is a soluble ESCRT-I component that is recruited to endosomal membranes during cargo sorting
      and MVB-related ESCRT activity.
    additional_reference_ids: *id020
    supported_by: *id021
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: IDA
  original_reference_id: PMID:11134028
  qualifier: located_in
  review:
    summary: cytosol localization is supported but broad and non-core.
    action: KEEP_AS_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.
    additional_reference_ids: *id018
    supported_by: *id019
- term:
    id: GO:0000045
    label: autophagosome assembly
  evidence_type: IMP
  original_reference_id: PMID:32424346
  qualifier: involved_in
  review:
    summary: VPS28 should be annotated to autophagosome assembly for ESCRT-I-dependent phagophore closure.
    action: NEW
    reason: VPS28 helical-interface mutations disrupt ESCRT-I filament assembly and cause an autophagosome
      closure defect; this is more precise than broad macroautophagy.
    additional_reference_ids: *id023
    supported_by: *id024
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:0000107
  title: Automatic transfer of experimentally verified manual GO annotation data to orthologs using Ensembl
    Compara
  findings: []
- id: GO_REF:0000117
  title: Electronic Gene Ontology annotations created by ARBA machine learning models
  findings: []
- id: GO_REF:0000120
  title: Combined Automated Annotation using Multiple IEA Methods
  findings: []
- id: PMID:11134028
  title: TSG101/mammalian VPS23 and mammalian VPS28 interact directly and are recruited to VPS4-induced
    endosomes.
  findings: []
- id: PMID:11916981
  title: Mammalian class E vps proteins recognize ubiquitin and act in the removal of endosomal
    protein-ubiquitin conjugates.
  findings: []
- id: PMID:14505570
  title: The protein network of HIV budding.
  findings: []
- id: PMID:14519844
  title: Divergent retroviral late-budding domains recruit vacuolar protein sorting factors by using
    alternative adaptor proteins.
  findings: []
- id: PMID:15218037
  title: The human endosomal sorting complex required for transport (ESCRT-I) and its role in HIV-1 budding.
  findings: []
- id: PMID:16189514
  title: Towards a proteome-scale map of the human protein-protein interaction network.
  findings: []
- id: PMID:17940959
  title: Involvement of vacuolar protein sorting pathway in Ebola virus release independent of TSG101
    interaction.
  findings: []
- id: PMID:18005716
  title: Identification of human MVB12 proteins as ESCRT-I subunits that function in HIV budding.
  findings: []
- id: PMID:18077552
  title: 'Regulation of Tsg101 expression by the steadiness box: a role of Tsg101-associated ligase.'
  findings: []
- id: PMID:19056867
  title: Large-scale proteomics and phosphoproteomics of urinary exosomes.
  findings: []
- id: PMID:19060904
  title: An empirical framework for binary interactome mapping.
  findings: []
- id: PMID:19199708
  title: Proteomic analysis of human parotid gland exosomes by multidimensional protein identification
    technology (MudPIT).
  findings: []
- id: PMID:20458337
  title: MHC class II-associated proteins in B-cell exosomes and potential functional implications for exosome
    biogenesis.
  findings: []
- id: PMID:20588296
  title: "Membrane budding and scission by the ESCRT machinery: it's all in the neck."
  findings: []
- id: PMID:20654576
  title: Distinct functions of human MVB12A and MVB12B in the ESCRT-I dependent on their posttranslational
    modifications.
  findings: []
- id: PMID:21516116
  title: Next-generation sequencing to generate interactome datasets.
  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:22232651
  title: Structural basis for membrane targeting by the MVB12-associated β-prism domain of the human ESCRT-I
    MVB12 subunit.
  findings: []
- id: PMID:23533145
  title: In-depth proteomic analyses of exosomes isolated from expressed prostatic secretions in urine.
  findings: []
- id: PMID:25416956
  title: A proteome-scale map of the human interactome network.
  findings: []
- id: PMID:25959826
  title: Quantitative interaction proteomics of neurodegenerative disease proteins.
  findings: []
- id: PMID:26871637
  title: Widespread Expansion of Protein Interaction Capabilities by Alternative Splicing.
  findings: []
- id: PMID:28514442
  title: Architecture of the human interactome defines protein communities and disease networks.
  findings: []
- id: PMID:31515488
  title: Extensive disruption of protein interactions by genetic variants across the allele frequency spectrum
    in human populations.
  findings: []
- id: PMID:32424346
  title: A helical assembly of human ESCRT-I scaffolds reverse-topology membrane scission.
  findings: []
- id: PMID:32814053
  title: Interactome Mapping Provides a Network of Neurodegenerative Disease Proteins and Uncovers Widespread
    Protein Aggregation in Affected Brains.
  findings: []
- id: PMID:33961781
  title: Dual proteome-scale networks reveal cell-specific remodeling of the human interactome.
  findings: []
- id: PMID:35271311
  title: 'OpenCell: Endogenous tagging for the cartography of human cellular organization.'
  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:31519728
  title: VPS37A directs ESCRT recruitment for phagophore closure.
  findings: []
- id: file:human/VPS28/VPS28-uniprot.txt
  title: UniProtKB record for human VPS28
  findings: []
- id: file:human/VPS28/VPS28-notes.md
  title: VPS28 review notes
  findings: []
core_functions:
- description: VPS28 is a structural/scaffold subunit of ESCRT-I that organizes the TSG101-VPS37-MVB12/UBAP
    ESCRT-I assembly for endosomal cargo sorting, MVB membrane remodeling, and ESCRT-I-dependent
    phagophore/autophagosome closure.
  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
  - id: GO:0090148
    label: membrane fission
  - id: GO:0000045
    label: autophagosome assembly
  locations:
  - id: GO:0010008
    label: endosome membrane
  - id: GO:0031902
    label: late endosome membrane
  - id: GO:0005768
    label: endosome
  in_complex:
    id: GO:0000813
    label: ESCRT I complex
  supported_by:
  - *id007
  - *id008
  - *id009
  - *id010
  - *id011
  - *id012
  - *id013
  - *id014
  - *id015
  - *id016
  - *id028
  - *id029
  - *id030
  - *id031
  - *id032
  - *id033
  - *id034
proposed_new_terms: []
suggested_questions:
- question: 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?
  experts:
  - GO molecular function editors
  - UniProt curators
- question: Should broad VPS28 macroautophagy annotations be replaced with GO:0000045 autophagosome assembly
    to capture ESCRT-I-dependent phagophore closure?
  experts:
  - GO autophagy editors
  - GO ESCRT curators
- question: Should viral budding, exosome, and plasma-membrane rows remain non-core in proteostasis-focused
    VPS28 curation?
  experts:
  - GO viral process editors
  - GO extracellular vesicle editors
suggested_experiments:
- experiment_type: VPS28 separation-of-function autophagosome closure assay
  hypothesis: The VPS28 helical interface is required for ESCRT-I accumulation and phagophore closure without
    abolishing assembly of individual ESCRT-I tetramers.
  description: 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.
- experiment_type: direct ubiquitin-binding assay for purified VPS28
  hypothesis: VPS28 does not independently bind ubiquitin; ubiquitin recognition by VPS28-containing ESCRT-I
    depends on TSG101 or other subunits.
  description: Compare purified VPS28, TSG101, and reconstituted ESCRT-I subcomplexes in quantitative
    ubiquitin-binding assays with matched positive and negative controls.

VPS28

Gene Description

Existing Annotations Review

Core Functions

VPS28 is a structural/scaffold subunit of ESCRT-I that organizes the TSG101-VPS37-MVB12/UBAP ESCRT-I assembly for endosomal cargo sorting, MVB membrane remodeling, and ESCRT-I-dependent phagophore/autophagosome closure.

References

Suggested Questions for Experts

Suggested Experiments

📚 Additional Documentation

Notes

VPS28 review notes

Scope

Evidence synthesis

Falcon

Description cleanup note

Pn Notes

VPS28 PN Consistency Notes

Source Files Checked

Deep Research Files

AIGR Review Snapshot

PN Consistency Summary

Full Consistency Review

PN Dossier Context

PN row 1: Autophagy-Lysosome Pathway | Autophagosome closure maturation and lysosome fusion | Sealing of autophagophore membrane | ESCRT-I complex component

Projected GO annotations (2)

Note

📄 View Raw YAML