TSG101

UniProt ID: Q99816
Organism: Homo sapiens
Review Status: COMPLETE
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Gene Description

TSG101 encodes the UEV-domain ESCRT-I subunit that binds ubiquitin/PTAP-type motifs and scaffolds ESCRT-I with VPS28, VPS37-family subunits, and MVB12/UBAP-family subunits. Its conserved core role is ESCRT-I-mediated sorting of ubiquitinated endocytic cargo into multivesicular bodies and reverse-topology membrane fission. TSG101 also participates in ESCRT-I-dependent phagophore/autophagosome closure, best represented biologically as autophagosome assembly rather than generic macroautophagy. Viral budding, cytokinesis, exosome release, and transcription/cell-growth annotations are supported non-core or over-broad branches.

Existing Annotations Review

GO Term Evidence Action Reason
GO:0000813 ESCRT I complex
IBA
GO_REF:0000033
ACCEPT
Summary: ESCRT-I complex membership is the central TSG101 cellular-component annotation.
Reason: TSG101 is a stoichiometric core ESCRT-I subunit with VPS28, VPS37-family subunits, and MVB12/UBAP-family subunits.
Supporting Evidence:
file:human/TSG101/TSG101-uniprot.txt
Component of the ESCRT-I complex
file:human/TSG101/TSG101-uniprot.txt
Binds to ubiquitinated cargo proteins
file:human/TSG101/TSG101-uniprot.txt
required for the sorting of endocytic ubiquitinated cargos into
file:human/TSG101/TSG101-uniprot.txt
which consists of TSG101, VPS28, a VPS37 protein
PMID:12900395
ESCRT-I subunit Tsg101
PMID:12900395
the initial recruitment of ESCRT-I to endosomes
GO:0008333 endosome to lysosome transport
IBA
GO_REF:0000033
ACCEPT
Summary: endosome to lysosome transport is supported as part of the core ESCRT-I endosomal cargo-sorting role.
Reason: TSG101/ESCRT-I sorts ubiquitinated endocytic cargo into MVBs and thereby supports endosome-to-lysosome/vacuolar delivery of cargo.
Supporting Evidence:
file:human/TSG101/TSG101-uniprot.txt
required for the sorting of endocytic ubiquitinated cargos into
file:human/TSG101/TSG101-uniprot.txt
multivesicular bodies
PMID:12900395
indirectly regulates multivesicular body formation
PMID:12900395
the initial recruitment of ESCRT-I to endosomes
GO:0000813 ESCRT I complex
IEA
GO_REF:0000117
ACCEPT
Summary: ESCRT-I complex membership is the central TSG101 cellular-component annotation.
Reason: TSG101 is a stoichiometric core ESCRT-I subunit with VPS28, VPS37-family subunits, and MVB12/UBAP-family subunits.
Supporting Evidence:
file:human/TSG101/TSG101-uniprot.txt
Component of the ESCRT-I complex
file:human/TSG101/TSG101-uniprot.txt
Binds to ubiquitinated cargo proteins
file:human/TSG101/TSG101-uniprot.txt
required for the sorting of endocytic ubiquitinated cargos into
file:human/TSG101/TSG101-uniprot.txt
which consists of TSG101, VPS28, a VPS37 protein
PMID:12900395
ESCRT-I subunit Tsg101
PMID:12900395
the initial recruitment of ESCRT-I to endosomes
GO:0005634 nucleus
IEA
GO_REF:0000044
KEEP AS NON CORE
Summary: nucleus localization is supported but is not the core proteostasis annotation.
Reason: These locations reflect broad cytosolic/nuclear/midbody/plasma-membrane contexts for TSG101 and ESCRT-associated functions, but the core review focus is ESCRT-I endosomal sorting and phagophore closure.
Supporting Evidence:
file:human/TSG101/TSG101-uniprot.txt
Mainly cytoplasmic
file:human/TSG101/TSG101-uniprot.txt
Nuclear localization is cell cycle-dependent
file:human/TSG101/TSG101-uniprot.txt
localization to the midbody during cytokinesis
GO:0005737 cytoplasm
IEA
GO_REF:0000120
KEEP AS NON CORE
Summary: cytoplasm localization is supported but is not the core proteostasis annotation.
Reason: These locations reflect broad cytosolic/nuclear/midbody/plasma-membrane contexts for TSG101 and ESCRT-associated functions, but the core review focus is ESCRT-I endosomal sorting and phagophore closure.
Supporting Evidence:
file:human/TSG101/TSG101-uniprot.txt
Mainly cytoplasmic
file:human/TSG101/TSG101-uniprot.txt
Nuclear localization is cell cycle-dependent
file:human/TSG101/TSG101-uniprot.txt
localization to the midbody during cytokinesis
GO:0005813 centrosome
IEA
GO_REF:0000044
KEEP AS NON CORE
Summary: centrosome localization is supported but is not the core proteostasis annotation.
Reason: These locations reflect broad cytosolic/nuclear/midbody/plasma-membrane contexts for TSG101 and ESCRT-associated functions, but the core review focus is ESCRT-I endosomal sorting and phagophore closure.
Supporting Evidence:
file:human/TSG101/TSG101-uniprot.txt
Mainly cytoplasmic
file:human/TSG101/TSG101-uniprot.txt
Nuclear localization is cell cycle-dependent
file:human/TSG101/TSG101-uniprot.txt
localization to the midbody during cytokinesis
GO:0006355 regulation of DNA-templated transcription
IEA
GO_REF:0000117
MARK AS OVER ANNOTATED
Summary: regulation of DNA-templated transcription is a legacy/non-core nuclear transcription annotation and likely overstates the current functional picture.
Reason: The synthesized evidence supports ESCRT-I ubiquitin/cargo sorting and membrane scission; DNA/transcription terms are not central and are not well integrated with the current proteostasis review.
Supporting Evidence:
file:human/TSG101/TSG101-uniprot.txt
May be involved in cell growth and differentiation
file:human/TSG101/TSG101-uniprot.txt
Acts as a negative growth regulator
GO:0015031 protein transport
IEA
GO_REF:0000002
MODIFY
Summary: Generic protein transport is true but should be replaced by MVB/endosome-to-lysosome cargo sorting terms.
Reason: The specific TSG101 transport role is ESCRT-I sorting of ubiquitinated cargo through MVB/endolysosomal pathways, not undifferentiated protein transport.
Supporting Evidence:
file:human/TSG101/TSG101-uniprot.txt
required for the sorting of endocytic ubiquitinated cargos into
file:human/TSG101/TSG101-uniprot.txt
multivesicular bodies
PMID:12900395
indirectly regulates multivesicular body formation
PMID:12900395
the initial recruitment of ESCRT-I to endosomes
GO:0016236 macroautophagy
IEA
GO_REF:0000117
MODIFY
Summary: macroautophagy is too broad or late-fusion-biased for the TSG101 autophagy role.
Reason: The best-supported PN autophagy interpretation is ESCRT-I-mediated phagophore/autophagosome closure, which is better represented by autophagosome assembly.
Proposed replacements: autophagosome assembly
Supporting Evidence:
PMID:31519728
VPS37A directs ESCRT recruitment for phagophore closure
PMID:31519728
the core ESCRT-I components TSG101 and VPS28
PMID:31519728
required for autophagosome completion
PMID:31519728
phagophore closure in mammalian cells
PMID:31010855
mediates AP sealing
PMID:31010855
ESCRT catalyzes AP closure
GO:0031901 early endosome membrane
IEA
GO_REF:0000044
ACCEPT
Summary: early endosome membrane localization is supported and relevant to ESCRT-I cargo sorting.
Reason: TSG101 cycles between cytosol and active endosomal membranes, including early/late endosome and MVB contexts where ESCRT-I functions.
Supporting Evidence:
file:human/TSG101/TSG101-uniprot.txt
Early endosome membrane
file:human/TSG101/TSG101-uniprot.txt
Late endosome membrane
PMID:12900395
Tsg101 to late endosomes
PMID:12900395
colocalize on a subpopulation of endosomes
GO:0031902 late endosome membrane
IEA
GO_REF:0000044
ACCEPT
Summary: late endosome membrane localization is supported and relevant to ESCRT-I cargo sorting.
Reason: TSG101 cycles between cytosol and active endosomal membranes, including early/late endosome and MVB contexts where ESCRT-I functions.
Supporting Evidence:
file:human/TSG101/TSG101-uniprot.txt
Early endosome membrane
file:human/TSG101/TSG101-uniprot.txt
Late endosome membrane
PMID:12900395
Tsg101 to late endosomes
PMID:12900395
colocalize on a subpopulation of endosomes
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: TSG101/ESCRT-I sorts ubiquitinated endocytic cargo into MVBs and thereby supports endosome-to-lysosome/vacuolar delivery of cargo.
Supporting Evidence:
file:human/TSG101/TSG101-uniprot.txt
required for the sorting of endocytic ubiquitinated cargos into
file:human/TSG101/TSG101-uniprot.txt
multivesicular bodies
PMID:12900395
indirectly regulates multivesicular body formation
PMID:12900395
the initial recruitment of ESCRT-I to endosomes
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 but reflects host-pathogen exploitation of ESCRT-I.
Reason: Viral budding/release annotations are well supported for TSG101 but are non-core for the human proteostasis-network review.
Supporting Evidence:
file:human/TSG101/TSG101-uniprot.txt
Involved in the budding of many viruses
file:human/TSG101/TSG101-uniprot.txt
interaction is essential for viral particle budding
PMID:11595185
required for HIV-1 budding
PMID:11595185
arrests HIV-1 budding at a late stage
GO:0045892 negative regulation of DNA-templated transcription
IEA
GO_REF:0000108
MARK AS OVER ANNOTATED
Summary: negative regulation of DNA-templated transcription is a legacy/non-core nuclear transcription annotation and likely overstates the current functional picture.
Reason: The synthesized evidence supports ESCRT-I ubiquitin/cargo sorting and membrane scission; DNA/transcription terms are not central and are not well integrated with the current proteostasis review.
Supporting Evidence:
file:human/TSG101/TSG101-uniprot.txt
May be involved in cell growth and differentiation
file:human/TSG101/TSG101-uniprot.txt
Acts as a negative growth regulator
GO:0090543 Flemming body
IEA
GO_REF:0000044
KEEP AS NON CORE
Summary: Flemming body localization is supported but is not the core proteostasis annotation.
Reason: These locations reflect broad cytosolic/nuclear/midbody/plasma-membrane contexts for TSG101 and ESCRT-associated functions, but the core review focus is ESCRT-I endosomal sorting and phagophore closure.
Supporting Evidence:
file:human/TSG101/TSG101-uniprot.txt
Mainly cytoplasmic
file:human/TSG101/TSG101-uniprot.txt
Nuclear localization is cell cycle-dependent
file:human/TSG101/TSG101-uniprot.txt
localization to the midbody during cytokinesis
GO:0005515 protein binding
IPI
PMID:12802020
TSG101 interaction with HRS mediates endosomal trafficking a...
MARK AS OVER ANNOTATED
Summary: protein binding is too generic to represent TSG101 function.
Reason: The interaction evidence should be represented by ubiquitin binding, ESCRT-I complex membership, MVB sorting, viral budding context, or cytokinesis context rather than generic binding terms.
Supporting Evidence:
file:human/TSG101/TSG101-uniprot.txt
Component of the ESCRT-I complex
file:human/TSG101/TSG101-uniprot.txt
Binds to ubiquitinated cargo proteins
file:human/TSG101/TSG101-uniprot.txt
required for the sorting of endocytic ubiquitinated cargos into
file:human/TSG101/TSG101-uniprot.txt
which consists of TSG101, VPS28, a VPS37 protein
PMID:12900395
ESCRT-I subunit Tsg101
PMID:12900395
the initial recruitment of ESCRT-I to endosomes
file:human/TSG101/TSG101-uniprot.txt
Binds to ubiquitinated cargo proteins
file:human/TSG101/TSG101-uniprot.txt
Interacts with ubiquitin
GO:0005515 protein binding
IPI
PMID:12900395
Hrs regulates multivesicular body formation via ESCRT recrui...
MARK AS OVER ANNOTATED
Summary: protein binding is too generic to represent TSG101 function.
Reason: The interaction evidence should be represented by ubiquitin binding, ESCRT-I complex membership, MVB sorting, viral budding context, or cytokinesis context rather than generic binding terms.
Supporting Evidence:
file:human/TSG101/TSG101-uniprot.txt
Component of the ESCRT-I complex
file:human/TSG101/TSG101-uniprot.txt
Binds to ubiquitinated cargo proteins
file:human/TSG101/TSG101-uniprot.txt
required for the sorting of endocytic ubiquitinated cargos into
file:human/TSG101/TSG101-uniprot.txt
which consists of TSG101, VPS28, a VPS37 protein
PMID:12900395
ESCRT-I subunit Tsg101
PMID:12900395
the initial recruitment of ESCRT-I to endosomes
file:human/TSG101/TSG101-uniprot.txt
Binds to ubiquitinated cargo proteins
file:human/TSG101/TSG101-uniprot.txt
Interacts with ubiquitin
GO:0005515 protein binding
IPI
PMID:15033475
Physical and functional interactions between Daxx and TSG101...
MARK AS OVER ANNOTATED
Summary: protein binding is too generic to represent TSG101 function.
Reason: The interaction evidence should be represented by ubiquitin binding, ESCRT-I complex membership, MVB sorting, viral budding context, or cytokinesis context rather than generic binding terms.
Supporting Evidence:
file:human/TSG101/TSG101-uniprot.txt
Component of the ESCRT-I complex
file:human/TSG101/TSG101-uniprot.txt
Binds to ubiquitinated cargo proteins
file:human/TSG101/TSG101-uniprot.txt
required for the sorting of endocytic ubiquitinated cargos into
file:human/TSG101/TSG101-uniprot.txt
which consists of TSG101, VPS28, a VPS37 protein
PMID:12900395
ESCRT-I subunit Tsg101
PMID:12900395
the initial recruitment of ESCRT-I to endosomes
file:human/TSG101/TSG101-uniprot.txt
Binds to ubiquitinated cargo proteins
file:human/TSG101/TSG101-uniprot.txt
Interacts with ubiquitin
GO:0005515 protein binding
IPI
PMID:15611048
Interactions of TOM1L1 with the multivesicular body sorting ...
MARK AS OVER ANNOTATED
Summary: protein binding is too generic to represent TSG101 function.
Reason: The interaction evidence should be represented by ubiquitin binding, ESCRT-I complex membership, MVB sorting, viral budding context, or cytokinesis context rather than generic binding terms.
Supporting Evidence:
file:human/TSG101/TSG101-uniprot.txt
Component of the ESCRT-I complex
file:human/TSG101/TSG101-uniprot.txt
Binds to ubiquitinated cargo proteins
file:human/TSG101/TSG101-uniprot.txt
required for the sorting of endocytic ubiquitinated cargos into
file:human/TSG101/TSG101-uniprot.txt
which consists of TSG101, VPS28, a VPS37 protein
PMID:12900395
ESCRT-I subunit Tsg101
PMID:12900395
the initial recruitment of ESCRT-I to endosomes
file:human/TSG101/TSG101-uniprot.txt
Binds to ubiquitinated cargo proteins
file:human/TSG101/TSG101-uniprot.txt
Interacts with ubiquitin
GO:0005515 protein binding
IPI
PMID:16118794
SIMPLE interacts with NEDD4 and TSG101: evidence for a role ...
MARK AS OVER ANNOTATED
Summary: protein binding is too generic to represent TSG101 function.
Reason: The interaction evidence should be represented by ubiquitin binding, ESCRT-I complex membership, MVB sorting, viral budding context, or cytokinesis context rather than generic binding terms.
Supporting Evidence:
file:human/TSG101/TSG101-uniprot.txt
Component of the ESCRT-I complex
file:human/TSG101/TSG101-uniprot.txt
Binds to ubiquitinated cargo proteins
file:human/TSG101/TSG101-uniprot.txt
required for the sorting of endocytic ubiquitinated cargos into
file:human/TSG101/TSG101-uniprot.txt
which consists of TSG101, VPS28, a VPS37 protein
PMID:12900395
ESCRT-I subunit Tsg101
PMID:12900395
the initial recruitment of ESCRT-I to endosomes
file:human/TSG101/TSG101-uniprot.txt
Binds to ubiquitinated cargo proteins
file:human/TSG101/TSG101-uniprot.txt
Interacts with ubiquitin
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 TSG101 function.
Reason: The interaction evidence should be represented by ubiquitin binding, ESCRT-I complex membership, MVB sorting, viral budding context, or cytokinesis context rather than generic binding terms.
Supporting Evidence:
file:human/TSG101/TSG101-uniprot.txt
Component of the ESCRT-I complex
file:human/TSG101/TSG101-uniprot.txt
Binds to ubiquitinated cargo proteins
file:human/TSG101/TSG101-uniprot.txt
required for the sorting of endocytic ubiquitinated cargos into
file:human/TSG101/TSG101-uniprot.txt
which consists of TSG101, VPS28, a VPS37 protein
PMID:12900395
ESCRT-I subunit Tsg101
PMID:12900395
the initial recruitment of ESCRT-I to endosomes
file:human/TSG101/TSG101-uniprot.txt
Binds to ubiquitinated cargo proteins
file:human/TSG101/TSG101-uniprot.txt
Interacts with ubiquitin
GO:0005515 protein binding
IPI
PMID:17174262
HD-PTP and Alix share some membrane-traffic related proteins...
MARK AS OVER ANNOTATED
Summary: protein binding is too generic to represent TSG101 function.
Reason: The interaction evidence should be represented by ubiquitin binding, ESCRT-I complex membership, MVB sorting, viral budding context, or cytokinesis context rather than generic binding terms.
Supporting Evidence:
file:human/TSG101/TSG101-uniprot.txt
Component of the ESCRT-I complex
file:human/TSG101/TSG101-uniprot.txt
Binds to ubiquitinated cargo proteins
file:human/TSG101/TSG101-uniprot.txt
required for the sorting of endocytic ubiquitinated cargos into
file:human/TSG101/TSG101-uniprot.txt
which consists of TSG101, VPS28, a VPS37 protein
PMID:12900395
ESCRT-I subunit Tsg101
PMID:12900395
the initial recruitment of ESCRT-I to endosomes
file:human/TSG101/TSG101-uniprot.txt
Binds to ubiquitinated cargo proteins
file:human/TSG101/TSG101-uniprot.txt
Interacts with ubiquitin
GO:0005515 protein binding
IPI
PMID:17350572
Structural and biochemical studies of ALIX/AIP1 and its role...
MARK AS OVER ANNOTATED
Summary: protein binding is too generic to represent TSG101 function.
Reason: The interaction evidence should be represented by ubiquitin binding, ESCRT-I complex membership, MVB sorting, viral budding context, or cytokinesis context rather than generic binding terms.
Supporting Evidence:
file:human/TSG101/TSG101-uniprot.txt
Component of the ESCRT-I complex
file:human/TSG101/TSG101-uniprot.txt
Binds to ubiquitinated cargo proteins
file:human/TSG101/TSG101-uniprot.txt
required for the sorting of endocytic ubiquitinated cargos into
file:human/TSG101/TSG101-uniprot.txt
which consists of TSG101, VPS28, a VPS37 protein
PMID:12900395
ESCRT-I subunit Tsg101
PMID:12900395
the initial recruitment of ESCRT-I to endosomes
file:human/TSG101/TSG101-uniprot.txt
Binds to ubiquitinated cargo proteins
file:human/TSG101/TSG101-uniprot.txt
Interacts with ubiquitin
GO:0005515 protein binding
IPI
PMID:17853893
Human ESCRT and ALIX proteins interact with proteins of the ...
MARK AS OVER ANNOTATED
Summary: protein binding is too generic to represent TSG101 function.
Reason: The interaction evidence should be represented by ubiquitin binding, ESCRT-I complex membership, MVB sorting, viral budding context, or cytokinesis context rather than generic binding terms.
Supporting Evidence:
file:human/TSG101/TSG101-uniprot.txt
Component of the ESCRT-I complex
file:human/TSG101/TSG101-uniprot.txt
Binds to ubiquitinated cargo proteins
file:human/TSG101/TSG101-uniprot.txt
required for the sorting of endocytic ubiquitinated cargos into
file:human/TSG101/TSG101-uniprot.txt
which consists of TSG101, VPS28, a VPS37 protein
PMID:12900395
ESCRT-I subunit Tsg101
PMID:12900395
the initial recruitment of ESCRT-I to endosomes
file:human/TSG101/TSG101-uniprot.txt
Binds to ubiquitinated cargo proteins
file:human/TSG101/TSG101-uniprot.txt
Interacts with ubiquitin
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 TSG101 function.
Reason: The interaction evidence should be represented by ubiquitin binding, ESCRT-I complex membership, MVB sorting, viral budding context, or cytokinesis context rather than generic binding terms.
Supporting Evidence:
file:human/TSG101/TSG101-uniprot.txt
Component of the ESCRT-I complex
file:human/TSG101/TSG101-uniprot.txt
Binds to ubiquitinated cargo proteins
file:human/TSG101/TSG101-uniprot.txt
required for the sorting of endocytic ubiquitinated cargos into
file:human/TSG101/TSG101-uniprot.txt
which consists of TSG101, VPS28, a VPS37 protein
PMID:12900395
ESCRT-I subunit Tsg101
PMID:12900395
the initial recruitment of ESCRT-I to endosomes
file:human/TSG101/TSG101-uniprot.txt
Binds to ubiquitinated cargo proteins
file:human/TSG101/TSG101-uniprot.txt
Interacts with ubiquitin
GO:0005515 protein binding
IPI
PMID:19549727
Analysis of the human E2 ubiquitin conjugating enzyme protei...
MARK AS OVER ANNOTATED
Summary: protein binding is too generic to represent TSG101 function.
Reason: The interaction evidence should be represented by ubiquitin binding, ESCRT-I complex membership, MVB sorting, viral budding context, or cytokinesis context rather than generic binding terms.
Supporting Evidence:
file:human/TSG101/TSG101-uniprot.txt
Component of the ESCRT-I complex
file:human/TSG101/TSG101-uniprot.txt
Binds to ubiquitinated cargo proteins
file:human/TSG101/TSG101-uniprot.txt
required for the sorting of endocytic ubiquitinated cargos into
file:human/TSG101/TSG101-uniprot.txt
which consists of TSG101, VPS28, a VPS37 protein
PMID:12900395
ESCRT-I subunit Tsg101
PMID:12900395
the initial recruitment of ESCRT-I to endosomes
file:human/TSG101/TSG101-uniprot.txt
Binds to ubiquitinated cargo proteins
file:human/TSG101/TSG101-uniprot.txt
Interacts with ubiquitin
GO:0005515 protein binding
IPI
PMID:20176808
TEX14 interacts with CEP55 to block cell abscission.
MARK AS OVER ANNOTATED
Summary: protein binding is too generic to represent TSG101 function.
Reason: The interaction evidence should be represented by ubiquitin binding, ESCRT-I complex membership, MVB sorting, viral budding context, or cytokinesis context rather than generic binding terms.
Supporting Evidence:
file:human/TSG101/TSG101-uniprot.txt
Component of the ESCRT-I complex
file:human/TSG101/TSG101-uniprot.txt
Binds to ubiquitinated cargo proteins
file:human/TSG101/TSG101-uniprot.txt
required for the sorting of endocytic ubiquitinated cargos into
file:human/TSG101/TSG101-uniprot.txt
which consists of TSG101, VPS28, a VPS37 protein
PMID:12900395
ESCRT-I subunit Tsg101
PMID:12900395
the initial recruitment of ESCRT-I to endosomes
file:human/TSG101/TSG101-uniprot.txt
Binds to ubiquitinated cargo proteins
file:human/TSG101/TSG101-uniprot.txt
Interacts with ubiquitin
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 TSG101 function.
Reason: The interaction evidence should be represented by ubiquitin binding, ESCRT-I complex membership, MVB sorting, viral budding context, or cytokinesis context rather than generic binding terms.
Supporting Evidence:
file:human/TSG101/TSG101-uniprot.txt
Component of the ESCRT-I complex
file:human/TSG101/TSG101-uniprot.txt
Binds to ubiquitinated cargo proteins
file:human/TSG101/TSG101-uniprot.txt
required for the sorting of endocytic ubiquitinated cargos into
file:human/TSG101/TSG101-uniprot.txt
which consists of TSG101, VPS28, a VPS37 protein
PMID:12900395
ESCRT-I subunit Tsg101
PMID:12900395
the initial recruitment of ESCRT-I to endosomes
file:human/TSG101/TSG101-uniprot.txt
Binds to ubiquitinated cargo proteins
file:human/TSG101/TSG101-uniprot.txt
Interacts with ubiquitin
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 TSG101 function.
Reason: The interaction evidence should be represented by ubiquitin binding, ESCRT-I complex membership, MVB sorting, viral budding context, or cytokinesis context rather than generic binding terms.
Supporting Evidence:
file:human/TSG101/TSG101-uniprot.txt
Component of the ESCRT-I complex
file:human/TSG101/TSG101-uniprot.txt
Binds to ubiquitinated cargo proteins
file:human/TSG101/TSG101-uniprot.txt
required for the sorting of endocytic ubiquitinated cargos into
file:human/TSG101/TSG101-uniprot.txt
which consists of TSG101, VPS28, a VPS37 protein
PMID:12900395
ESCRT-I subunit Tsg101
PMID:12900395
the initial recruitment of ESCRT-I to endosomes
file:human/TSG101/TSG101-uniprot.txt
Binds to ubiquitinated cargo proteins
file:human/TSG101/TSG101-uniprot.txt
Interacts with ubiquitin
GO:0005515 protein binding
IPI
PMID:27107012
Pooled-matrix protein interaction screens using Barcode Fusi...
MARK AS OVER ANNOTATED
Summary: protein binding is too generic to represent TSG101 function.
Reason: The interaction evidence should be represented by ubiquitin binding, ESCRT-I complex membership, MVB sorting, viral budding context, or cytokinesis context rather than generic binding terms.
Supporting Evidence:
file:human/TSG101/TSG101-uniprot.txt
Component of the ESCRT-I complex
file:human/TSG101/TSG101-uniprot.txt
Binds to ubiquitinated cargo proteins
file:human/TSG101/TSG101-uniprot.txt
required for the sorting of endocytic ubiquitinated cargos into
file:human/TSG101/TSG101-uniprot.txt
which consists of TSG101, VPS28, a VPS37 protein
PMID:12900395
ESCRT-I subunit Tsg101
PMID:12900395
the initial recruitment of ESCRT-I to endosomes
file:human/TSG101/TSG101-uniprot.txt
Binds to ubiquitinated cargo proteins
file:human/TSG101/TSG101-uniprot.txt
Interacts with ubiquitin
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 TSG101 function.
Reason: The interaction evidence should be represented by ubiquitin binding, ESCRT-I complex membership, MVB sorting, viral budding context, or cytokinesis context rather than generic binding terms.
Supporting Evidence:
file:human/TSG101/TSG101-uniprot.txt
Component of the ESCRT-I complex
file:human/TSG101/TSG101-uniprot.txt
Binds to ubiquitinated cargo proteins
file:human/TSG101/TSG101-uniprot.txt
required for the sorting of endocytic ubiquitinated cargos into
file:human/TSG101/TSG101-uniprot.txt
which consists of TSG101, VPS28, a VPS37 protein
PMID:12900395
ESCRT-I subunit Tsg101
PMID:12900395
the initial recruitment of ESCRT-I to endosomes
file:human/TSG101/TSG101-uniprot.txt
Binds to ubiquitinated cargo proteins
file:human/TSG101/TSG101-uniprot.txt
Interacts with ubiquitin
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 TSG101 function.
Reason: The interaction evidence should be represented by ubiquitin binding, ESCRT-I complex membership, MVB sorting, viral budding context, or cytokinesis context rather than generic binding terms.
Supporting Evidence:
file:human/TSG101/TSG101-uniprot.txt
Component of the ESCRT-I complex
file:human/TSG101/TSG101-uniprot.txt
Binds to ubiquitinated cargo proteins
file:human/TSG101/TSG101-uniprot.txt
required for the sorting of endocytic ubiquitinated cargos into
file:human/TSG101/TSG101-uniprot.txt
which consists of TSG101, VPS28, a VPS37 protein
PMID:12900395
ESCRT-I subunit Tsg101
PMID:12900395
the initial recruitment of ESCRT-I to endosomes
file:human/TSG101/TSG101-uniprot.txt
Binds to ubiquitinated cargo proteins
file:human/TSG101/TSG101-uniprot.txt
Interacts with ubiquitin
GO:0005515 protein binding
IPI
PMID:32296183
A reference map of the human binary protein interactome.
MARK AS OVER ANNOTATED
Summary: protein binding is too generic to represent TSG101 function.
Reason: The interaction evidence should be represented by ubiquitin binding, ESCRT-I complex membership, MVB sorting, viral budding context, or cytokinesis context rather than generic binding terms.
Supporting Evidence:
file:human/TSG101/TSG101-uniprot.txt
Component of the ESCRT-I complex
file:human/TSG101/TSG101-uniprot.txt
Binds to ubiquitinated cargo proteins
file:human/TSG101/TSG101-uniprot.txt
required for the sorting of endocytic ubiquitinated cargos into
file:human/TSG101/TSG101-uniprot.txt
which consists of TSG101, VPS28, a VPS37 protein
PMID:12900395
ESCRT-I subunit Tsg101
PMID:12900395
the initial recruitment of ESCRT-I to endosomes
file:human/TSG101/TSG101-uniprot.txt
Binds to ubiquitinated cargo proteins
file:human/TSG101/TSG101-uniprot.txt
Interacts with ubiquitin
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 TSG101 function.
Reason: The interaction evidence should be represented by ubiquitin binding, ESCRT-I complex membership, MVB sorting, viral budding context, or cytokinesis context rather than generic binding terms.
Supporting Evidence:
file:human/TSG101/TSG101-uniprot.txt
Component of the ESCRT-I complex
file:human/TSG101/TSG101-uniprot.txt
Binds to ubiquitinated cargo proteins
file:human/TSG101/TSG101-uniprot.txt
required for the sorting of endocytic ubiquitinated cargos into
file:human/TSG101/TSG101-uniprot.txt
which consists of TSG101, VPS28, a VPS37 protein
PMID:12900395
ESCRT-I subunit Tsg101
PMID:12900395
the initial recruitment of ESCRT-I to endosomes
file:human/TSG101/TSG101-uniprot.txt
Binds to ubiquitinated cargo proteins
file:human/TSG101/TSG101-uniprot.txt
Interacts with ubiquitin
GO:0005515 protein binding
IPI
PMID:35044719
Proteome-scale mapping of binding sites in the unstructured ...
MARK AS OVER ANNOTATED
Summary: protein binding is too generic to represent TSG101 function.
Reason: The interaction evidence should be represented by ubiquitin binding, ESCRT-I complex membership, MVB sorting, viral budding context, or cytokinesis context rather than generic binding terms.
Supporting Evidence:
file:human/TSG101/TSG101-uniprot.txt
Component of the ESCRT-I complex
file:human/TSG101/TSG101-uniprot.txt
Binds to ubiquitinated cargo proteins
file:human/TSG101/TSG101-uniprot.txt
required for the sorting of endocytic ubiquitinated cargos into
file:human/TSG101/TSG101-uniprot.txt
which consists of TSG101, VPS28, a VPS37 protein
PMID:12900395
ESCRT-I subunit Tsg101
PMID:12900395
the initial recruitment of ESCRT-I to endosomes
file:human/TSG101/TSG101-uniprot.txt
Binds to ubiquitinated cargo proteins
file:human/TSG101/TSG101-uniprot.txt
Interacts with ubiquitin
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 TSG101 function.
Reason: The interaction evidence should be represented by ubiquitin binding, ESCRT-I complex membership, MVB sorting, viral budding context, or cytokinesis context rather than generic binding terms.
Supporting Evidence:
file:human/TSG101/TSG101-uniprot.txt
Component of the ESCRT-I complex
file:human/TSG101/TSG101-uniprot.txt
Binds to ubiquitinated cargo proteins
file:human/TSG101/TSG101-uniprot.txt
required for the sorting of endocytic ubiquitinated cargos into
file:human/TSG101/TSG101-uniprot.txt
which consists of TSG101, VPS28, a VPS37 protein
PMID:12900395
ESCRT-I subunit Tsg101
PMID:12900395
the initial recruitment of ESCRT-I to endosomes
file:human/TSG101/TSG101-uniprot.txt
Binds to ubiquitinated cargo proteins
file:human/TSG101/TSG101-uniprot.txt
Interacts with ubiquitin
GO:0005515 protein binding
IPI
PMID:37100772
Large-scale phage-based screening reveals extensive pan-vira...
MARK AS OVER ANNOTATED
Summary: protein binding is too generic to represent TSG101 function.
Reason: The interaction evidence should be represented by ubiquitin binding, ESCRT-I complex membership, MVB sorting, viral budding context, or cytokinesis context rather than generic binding terms.
Supporting Evidence:
file:human/TSG101/TSG101-uniprot.txt
Component of the ESCRT-I complex
file:human/TSG101/TSG101-uniprot.txt
Binds to ubiquitinated cargo proteins
file:human/TSG101/TSG101-uniprot.txt
required for the sorting of endocytic ubiquitinated cargos into
file:human/TSG101/TSG101-uniprot.txt
which consists of TSG101, VPS28, a VPS37 protein
PMID:12900395
ESCRT-I subunit Tsg101
PMID:12900395
the initial recruitment of ESCRT-I to endosomes
file:human/TSG101/TSG101-uniprot.txt
Binds to ubiquitinated cargo proteins
file:human/TSG101/TSG101-uniprot.txt
Interacts with ubiquitin
GO:0005515 protein binding
IPI
PMID:37219487
Large-scale phosphomimetic screening identifies phospho-modu...
MARK AS OVER ANNOTATED
Summary: protein binding is too generic to represent TSG101 function.
Reason: The interaction evidence should be represented by ubiquitin binding, ESCRT-I complex membership, MVB sorting, viral budding context, or cytokinesis context rather than generic binding terms.
Supporting Evidence:
file:human/TSG101/TSG101-uniprot.txt
Component of the ESCRT-I complex
file:human/TSG101/TSG101-uniprot.txt
Binds to ubiquitinated cargo proteins
file:human/TSG101/TSG101-uniprot.txt
required for the sorting of endocytic ubiquitinated cargos into
file:human/TSG101/TSG101-uniprot.txt
which consists of TSG101, VPS28, a VPS37 protein
PMID:12900395
ESCRT-I subunit Tsg101
PMID:12900395
the initial recruitment of ESCRT-I to endosomes
file:human/TSG101/TSG101-uniprot.txt
Binds to ubiquitinated cargo proteins
file:human/TSG101/TSG101-uniprot.txt
Interacts with ubiquitin
GO:0005515 protein binding
IPI
PMID:39526800
A comprehensive two-hybrid analysis to explore the Legionell...
MARK AS OVER ANNOTATED
Summary: protein binding is too generic to represent TSG101 function.
Reason: The interaction evidence should be represented by ubiquitin binding, ESCRT-I complex membership, MVB sorting, viral budding context, or cytokinesis context rather than generic binding terms.
Supporting Evidence:
file:human/TSG101/TSG101-uniprot.txt
Component of the ESCRT-I complex
file:human/TSG101/TSG101-uniprot.txt
Binds to ubiquitinated cargo proteins
file:human/TSG101/TSG101-uniprot.txt
required for the sorting of endocytic ubiquitinated cargos into
file:human/TSG101/TSG101-uniprot.txt
which consists of TSG101, VPS28, a VPS37 protein
PMID:12900395
ESCRT-I subunit Tsg101
PMID:12900395
the initial recruitment of ESCRT-I to endosomes
file:human/TSG101/TSG101-uniprot.txt
Binds to ubiquitinated cargo proteins
file:human/TSG101/TSG101-uniprot.txt
Interacts with ubiquitin
GO:0005515 protein binding
IPI
PMID:40205054
Multimodal cell maps as a foundation for structural and func...
MARK AS OVER ANNOTATED
Summary: protein binding is too generic to represent TSG101 function.
Reason: The interaction evidence should be represented by ubiquitin binding, ESCRT-I complex membership, MVB sorting, viral budding context, or cytokinesis context rather than generic binding terms.
Supporting Evidence:
file:human/TSG101/TSG101-uniprot.txt
Component of the ESCRT-I complex
file:human/TSG101/TSG101-uniprot.txt
Binds to ubiquitinated cargo proteins
file:human/TSG101/TSG101-uniprot.txt
required for the sorting of endocytic ubiquitinated cargos into
file:human/TSG101/TSG101-uniprot.txt
which consists of TSG101, VPS28, a VPS37 protein
PMID:12900395
ESCRT-I subunit Tsg101
PMID:12900395
the initial recruitment of ESCRT-I to endosomes
file:human/TSG101/TSG101-uniprot.txt
Binds to ubiquitinated cargo proteins
file:human/TSG101/TSG101-uniprot.txt
Interacts with ubiquitin
GO:0003714 transcription corepressor activity
IEA
GO_REF:0000107
MARK AS OVER ANNOTATED
Summary: transcription corepressor activity is a legacy/non-core nuclear transcription annotation and likely overstates the current functional picture.
Reason: The synthesized evidence supports ESCRT-I ubiquitin/cargo sorting and membrane scission; DNA/transcription terms are not central and are not well integrated with the current proteostasis review.
Supporting Evidence:
file:human/TSG101/TSG101-uniprot.txt
May be involved in cell growth and differentiation
file:human/TSG101/TSG101-uniprot.txt
Acts as a negative growth regulator
GO:0046755 viral budding
IEA
GO_REF:0000107
KEEP AS NON CORE
Summary: viral budding is supported but reflects host-pathogen exploitation of ESCRT-I.
Reason: Viral budding/release annotations are well supported for TSG101 but are non-core for the human proteostasis-network review.
Supporting Evidence:
file:human/TSG101/TSG101-uniprot.txt
Involved in the budding of many viruses
file:human/TSG101/TSG101-uniprot.txt
interaction is essential for viral particle budding
PMID:11595185
required for HIV-1 budding
PMID:11595185
arrests HIV-1 budding at a late stage
GO:0070062 extracellular exosome
IEA
GO_REF:0000107
KEEP AS NON CORE
Summary: Extracellular exosome detection is supported but is a non-core localization/context.
Reason: TSG101 is commonly detected in exosome preparations and regulates exosomal release, but this is secondary to its ESCRT-I membrane-remodeling role.
Supporting Evidence:
file:human/TSG101/TSG101-uniprot.txt
Required for the exosomal release of SDCBP, CD63 and syndecan
file:human/TSG101/TSG101-uniprot.txt
extracellular release of microvesicles
GO:1990182 exosomal secretion
IEA
GO_REF:0000107
KEEP AS NON CORE
Summary: exosomal secretion is supported but non-core in this PN review.
Reason: TSG101 contributes to exosome/microvesicle release, but the proteostasis core here is ESCRT-I endosomal cargo sorting and autophagophore closure.
Supporting Evidence:
file:human/TSG101/TSG101-uniprot.txt
Required for the exosomal release of SDCBP, CD63 and syndecan
file:human/TSG101/TSG101-uniprot.txt
extracellular release of microvesicles
GO:2000397 positive regulation of ubiquitin-dependent endocytosis
IEA
GO_REF:0000107
ACCEPT
Summary: positive regulation of ubiquitin-dependent endocytosis is supported as a cargo-sorting consequence of ESCRT-I function.
Reason: TSG101-mediated ESCRT-I sorting of ubiquitinated receptors into the MVB/lysosomal pathway explains EGFR/endocytosis down-regulation annotations.
Supporting Evidence:
file:human/TSG101/TSG101-uniprot.txt
required for the sorting of endocytic ubiquitinated cargos into
file:human/TSG101/TSG101-uniprot.txt
multivesicular bodies
PMID:12900395
indirectly regulates multivesicular body formation
PMID:12900395
the initial recruitment of ESCRT-I to endosomes
GO:0005829 cytosol
IDA
GO_REF:0000052
KEEP AS NON CORE
Summary: cytosol localization is supported but is not the core proteostasis annotation.
Reason: These locations reflect broad cytosolic/nuclear/midbody/plasma-membrane contexts for TSG101 and ESCRT-associated functions, but the core review focus is ESCRT-I endosomal sorting and phagophore closure.
Supporting Evidence:
file:human/TSG101/TSG101-uniprot.txt
Mainly cytoplasmic
file:human/TSG101/TSG101-uniprot.txt
Nuclear localization is cell cycle-dependent
file:human/TSG101/TSG101-uniprot.txt
localization to the midbody during cytokinesis
GO:0005634 nucleus
EXP
PMID:17229889
Spongiform neurodegeneration-associated E3 ligase Mahogunin ...
KEEP AS NON CORE
Summary: nucleus localization is supported but is not the core proteostasis annotation.
Reason: These locations reflect broad cytosolic/nuclear/midbody/plasma-membrane contexts for TSG101 and ESCRT-associated functions, but the core review focus is ESCRT-I endosomal sorting and phagophore closure.
Supporting Evidence:
file:human/TSG101/TSG101-uniprot.txt
Mainly cytoplasmic
file:human/TSG101/TSG101-uniprot.txt
Nuclear localization is cell cycle-dependent
file:human/TSG101/TSG101-uniprot.txt
localization to the midbody during cytokinesis
GO:0005737 cytoplasm
EXP
PMID:17853893
Human ESCRT and ALIX proteins interact with proteins of the ...
KEEP AS NON CORE
Summary: cytoplasm localization is supported but is not the core proteostasis annotation.
Reason: These locations reflect broad cytosolic/nuclear/midbody/plasma-membrane contexts for TSG101 and ESCRT-associated functions, but the core review focus is ESCRT-I endosomal sorting and phagophore closure.
Supporting Evidence:
file:human/TSG101/TSG101-uniprot.txt
Mainly cytoplasmic
file:human/TSG101/TSG101-uniprot.txt
Nuclear localization is cell cycle-dependent
file:human/TSG101/TSG101-uniprot.txt
localization to the midbody during cytokinesis
GO:0031901 early endosome membrane
EXP
PMID:23166352
Charcot-Marie-Tooth disease-linked protein SIMPLE functions ...
ACCEPT
Summary: early endosome membrane localization is supported and relevant to ESCRT-I cargo sorting.
Reason: TSG101 cycles between cytosol and active endosomal membranes, including early/late endosome and MVB contexts where ESCRT-I functions.
Supporting Evidence:
file:human/TSG101/TSG101-uniprot.txt
Early endosome membrane
file:human/TSG101/TSG101-uniprot.txt
Late endosome membrane
PMID:12900395
Tsg101 to late endosomes
PMID:12900395
colocalize on a subpopulation of endosomes
GO:0031902 late endosome membrane
EXP
PMID:11916981
Mammalian class E vps proteins recognize ubiquitin and act i...
ACCEPT
Summary: late endosome membrane localization is supported and relevant to ESCRT-I cargo sorting.
Reason: TSG101 cycles between cytosol and active endosomal membranes, including early/late endosome and MVB contexts where ESCRT-I functions.
Supporting Evidence:
file:human/TSG101/TSG101-uniprot.txt
Early endosome membrane
file:human/TSG101/TSG101-uniprot.txt
Late endosome membrane
PMID:12900395
Tsg101 to late endosomes
PMID:12900395
colocalize on a subpopulation of endosomes
GO:0031902 late endosome membrane
EXP
PMID:17229889
Spongiform neurodegeneration-associated E3 ligase Mahogunin ...
ACCEPT
Summary: late endosome membrane localization is supported and relevant to ESCRT-I cargo sorting.
Reason: TSG101 cycles between cytosol and active endosomal membranes, including early/late endosome and MVB contexts where ESCRT-I functions.
Supporting Evidence:
file:human/TSG101/TSG101-uniprot.txt
Early endosome membrane
file:human/TSG101/TSG101-uniprot.txt
Late endosome membrane
PMID:12900395
Tsg101 to late endosomes
PMID:12900395
colocalize on a subpopulation of endosomes
GO:0061631 ubiquitin conjugating enzyme activity
IKR NOT
PMID:9241264
TSG101 may be the prototype of a class of dominant negative ...
ACCEPT
Summary: The negated ubiquitin-conjugating-enzyme annotation is correct for TSG101.
Reason: This is a NOT annotation. TSG101 is a UEV-domain protein that binds ubiquitin/PTAP motifs but should not be curated as an active catalytic ubiquitin-conjugating enzyme.
Supporting Evidence:
file:human/TSG101/TSG101-uniprot.txt
The UEV domain binds ubiquitin
file:human/TSG101/TSG101-uniprot.txt
P-[ST]-A-P peptide motif independently
file:human/TSG101/TSG101-uniprot.txt
Belongs to the ubiquitin-conjugating enzyme family. UEV
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 TSG101 cellular-component annotation.
Reason: TSG101 is a stoichiometric core ESCRT-I subunit with VPS28, VPS37-family subunits, and MVB12/UBAP-family subunits.
Supporting Evidence:
file:human/TSG101/TSG101-uniprot.txt
Component of the ESCRT-I complex
file:human/TSG101/TSG101-uniprot.txt
Binds to ubiquitinated cargo proteins
file:human/TSG101/TSG101-uniprot.txt
required for the sorting of endocytic ubiquitinated cargos into
file:human/TSG101/TSG101-uniprot.txt
which consists of TSG101, VPS28, a VPS37 protein
PMID:12900395
ESCRT-I subunit Tsg101
PMID:12900395
the initial recruitment of ESCRT-I to endosomes
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 TSG101 cellular-component annotation.
Reason: TSG101 is a stoichiometric core ESCRT-I subunit with VPS28, VPS37-family subunits, and MVB12/UBAP-family subunits.
Supporting Evidence:
file:human/TSG101/TSG101-uniprot.txt
Component of the ESCRT-I complex
file:human/TSG101/TSG101-uniprot.txt
Binds to ubiquitinated cargo proteins
file:human/TSG101/TSG101-uniprot.txt
required for the sorting of endocytic ubiquitinated cargos into
file:human/TSG101/TSG101-uniprot.txt
which consists of TSG101, VPS28, a VPS37 protein
PMID:12900395
ESCRT-I subunit Tsg101
PMID:12900395
the initial recruitment of ESCRT-I to endosomes
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 TSG101 cellular-component annotation.
Reason: TSG101 is a stoichiometric core ESCRT-I subunit with VPS28, VPS37-family subunits, and MVB12/UBAP-family subunits.
Supporting Evidence:
file:human/TSG101/TSG101-uniprot.txt
Component of the ESCRT-I complex
file:human/TSG101/TSG101-uniprot.txt
Binds to ubiquitinated cargo proteins
file:human/TSG101/TSG101-uniprot.txt
required for the sorting of endocytic ubiquitinated cargos into
file:human/TSG101/TSG101-uniprot.txt
which consists of TSG101, VPS28, a VPS37 protein
PMID:12900395
ESCRT-I subunit Tsg101
PMID:12900395
the initial recruitment of ESCRT-I to endosomes
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 ESCRT-I cargo sorting.
Reason: TSG101 cycles between cytosol and active endosomal membranes, including early/late endosome and MVB contexts where ESCRT-I functions.
Supporting Evidence:
file:human/TSG101/TSG101-uniprot.txt
Early endosome membrane
file:human/TSG101/TSG101-uniprot.txt
Late endosome membrane
PMID:12900395
Tsg101 to late endosomes
PMID:12900395
colocalize on a subpopulation of endosomes
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: TSG101/ESCRT-I sorts ubiquitinated endocytic cargo into MVBs and thereby supports endosome-to-lysosome/vacuolar delivery of cargo.
Supporting Evidence:
file:human/TSG101/TSG101-uniprot.txt
required for the sorting of endocytic ubiquitinated cargos into
file:human/TSG101/TSG101-uniprot.txt
multivesicular bodies
PMID:12900395
indirectly regulates multivesicular body formation
PMID:12900395
the initial recruitment of ESCRT-I to endosomes
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: TSG101/ESCRT-I sorts ubiquitinated endocytic cargo into MVBs and thereby supports endosome-to-lysosome/vacuolar delivery of cargo.
Supporting Evidence:
file:human/TSG101/TSG101-uniprot.txt
required for the sorting of endocytic ubiquitinated cargos into
file:human/TSG101/TSG101-uniprot.txt
multivesicular bodies
PMID:12900395
indirectly regulates multivesicular body formation
PMID:12900395
the initial recruitment of ESCRT-I to endosomes
GO:0090148 membrane fission
NAS
PMID:32424346
A helical assembly of human ESCRT-I scaffolds reverse-topolo...
ACCEPT
Summary: Membrane fission is supported as the shared ESCRT reverse-topology membrane-remodeling activity.
Reason: ESCRT-I participates upstream of ESCRT-III/VPS4-driven neck scission in MVB formation, cytokinesis/viral budding, and phagophore closure contexts.
Supporting Evidence:
PMID:20588296
ESCRT-I and ESCRT-II direct membrane budding away from the cytosol
PMID:31519728
ESCRT-mediated membrane scission in phagophore closure
PMID:31519728
the core ESCRT-I components TSG101 and VPS28
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 TSG101 function.
Reason: The interaction evidence should be represented by ubiquitin binding, ESCRT-I complex membership, MVB sorting, viral budding context, or cytokinesis context rather than generic binding terms.
Supporting Evidence:
file:human/TSG101/TSG101-uniprot.txt
Component of the ESCRT-I complex
file:human/TSG101/TSG101-uniprot.txt
Binds to ubiquitinated cargo proteins
file:human/TSG101/TSG101-uniprot.txt
required for the sorting of endocytic ubiquitinated cargos into
file:human/TSG101/TSG101-uniprot.txt
which consists of TSG101, VPS28, a VPS37 protein
PMID:12900395
ESCRT-I subunit Tsg101
PMID:12900395
the initial recruitment of ESCRT-I to endosomes
file:human/TSG101/TSG101-uniprot.txt
Binds to ubiquitinated cargo proteins
file:human/TSG101/TSG101-uniprot.txt
Interacts with ubiquitin
GO:1903774 positive regulation of viral budding via host ESCRT complex
IMP
PMID:11595185
Tsg101 and the vacuolar protein sorting pathway are essentia...
KEEP AS NON CORE
Summary: positive regulation of viral budding via host ESCRT complex is supported but reflects host-pathogen exploitation of ESCRT-I.
Reason: Viral budding/release annotations are well supported for TSG101 but are non-core for the human proteostasis-network review.
Supporting Evidence:
file:human/TSG101/TSG101-uniprot.txt
Involved in the budding of many viruses
file:human/TSG101/TSG101-uniprot.txt
interaction is essential for viral particle budding
PMID:11595185
required for HIV-1 budding
PMID:11595185
arrests HIV-1 budding at a late stage
GO:0005515 protein binding
IPI
PMID:18005716
Identification of human MVB12 proteins as ESCRT-I subunits t...
MARK AS OVER ANNOTATED
Summary: protein binding is too generic to represent TSG101 function.
Reason: The interaction evidence should be represented by ubiquitin binding, ESCRT-I complex membership, MVB sorting, viral budding context, or cytokinesis context rather than generic binding terms.
Supporting Evidence:
file:human/TSG101/TSG101-uniprot.txt
Component of the ESCRT-I complex
file:human/TSG101/TSG101-uniprot.txt
Binds to ubiquitinated cargo proteins
file:human/TSG101/TSG101-uniprot.txt
required for the sorting of endocytic ubiquitinated cargos into
file:human/TSG101/TSG101-uniprot.txt
which consists of TSG101, VPS28, a VPS37 protein
PMID:12900395
ESCRT-I subunit Tsg101
PMID:12900395
the initial recruitment of ESCRT-I to endosomes
file:human/TSG101/TSG101-uniprot.txt
Binds to ubiquitinated cargo proteins
file:human/TSG101/TSG101-uniprot.txt
Interacts with ubiquitin
GO:0046755 viral budding
IMP
PMID:18005716
Identification of human MVB12 proteins as ESCRT-I subunits t...
KEEP AS NON CORE
Summary: viral budding is supported but reflects host-pathogen exploitation of ESCRT-I.
Reason: Viral budding/release annotations are well supported for TSG101 but are non-core for the human proteostasis-network review.
Supporting Evidence:
file:human/TSG101/TSG101-uniprot.txt
Involved in the budding of many viruses
file:human/TSG101/TSG101-uniprot.txt
interaction is essential for viral particle budding
PMID:11595185
required for HIV-1 budding
PMID:11595185
arrests HIV-1 budding at a late stage
GO:0005515 protein binding
IPI
PMID:22315426
Formation and release of arrestin domain-containing protein ...
MARK AS OVER ANNOTATED
Summary: protein binding is too generic to represent TSG101 function.
Reason: The interaction evidence should be represented by ubiquitin binding, ESCRT-I complex membership, MVB sorting, viral budding context, or cytokinesis context rather than generic binding terms.
Supporting Evidence:
file:human/TSG101/TSG101-uniprot.txt
Component of the ESCRT-I complex
file:human/TSG101/TSG101-uniprot.txt
Binds to ubiquitinated cargo proteins
file:human/TSG101/TSG101-uniprot.txt
required for the sorting of endocytic ubiquitinated cargos into
file:human/TSG101/TSG101-uniprot.txt
which consists of TSG101, VPS28, a VPS37 protein
PMID:12900395
ESCRT-I subunit Tsg101
PMID:12900395
the initial recruitment of ESCRT-I to endosomes
file:human/TSG101/TSG101-uniprot.txt
Binds to ubiquitinated cargo proteins
file:human/TSG101/TSG101-uniprot.txt
Interacts with ubiquitin
GO:0006858 extracellular transport
IMP
PMID:22315426
Formation and release of arrestin domain-containing protein ...
KEEP AS NON CORE
Summary: extracellular transport is supported but non-core in this PN review.
Reason: TSG101 contributes to exosome/microvesicle release, but the proteostasis core here is ESCRT-I endosomal cargo sorting and autophagophore closure.
Supporting Evidence:
file:human/TSG101/TSG101-uniprot.txt
Required for the exosomal release of SDCBP, CD63 and syndecan
file:human/TSG101/TSG101-uniprot.txt
extracellular release of microvesicles
GO:0007175 negative regulation of epidermal growth factor-activated receptor activity
IMP
PMID:16973552
Human ESCRT-II complex and its role in human immunodeficienc...
ACCEPT
Summary: negative regulation of epidermal growth factor-activated receptor activity is supported as a cargo-sorting consequence of ESCRT-I function.
Reason: TSG101-mediated ESCRT-I sorting of ubiquitinated receptors into the MVB/lysosomal pathway explains EGFR/endocytosis down-regulation annotations.
Supporting Evidence:
file:human/TSG101/TSG101-uniprot.txt
required for the sorting of endocytic ubiquitinated cargos into
file:human/TSG101/TSG101-uniprot.txt
multivesicular bodies
PMID:12900395
indirectly regulates multivesicular body formation
PMID:12900395
the initial recruitment of ESCRT-I to endosomes
GO:0044877 protein-containing complex binding
IDA
PMID:16973552
Human ESCRT-II complex and its role in human immunodeficienc...
MARK AS OVER ANNOTATED
Summary: protein-containing complex binding is too generic to represent TSG101 function.
Reason: The interaction evidence should be represented by ubiquitin binding, ESCRT-I complex membership, MVB sorting, viral budding context, or cytokinesis context rather than generic binding terms.
Supporting Evidence:
file:human/TSG101/TSG101-uniprot.txt
Component of the ESCRT-I complex
file:human/TSG101/TSG101-uniprot.txt
Binds to ubiquitinated cargo proteins
file:human/TSG101/TSG101-uniprot.txt
required for the sorting of endocytic ubiquitinated cargos into
file:human/TSG101/TSG101-uniprot.txt
which consists of TSG101, VPS28, a VPS37 protein
PMID:12900395
ESCRT-I subunit Tsg101
PMID:12900395
the initial recruitment of ESCRT-I to endosomes
file:human/TSG101/TSG101-uniprot.txt
Binds to ubiquitinated cargo proteins
file:human/TSG101/TSG101-uniprot.txt
Interacts with ubiquitin
GO:0005515 protein binding
IPI
PMID:18641129
Differential requirements for Alix and ESCRT-III in cytokine...
MARK AS OVER ANNOTATED
Summary: protein binding is too generic to represent TSG101 function.
Reason: The interaction evidence should be represented by ubiquitin binding, ESCRT-I complex membership, MVB sorting, viral budding context, or cytokinesis context rather than generic binding terms.
Supporting Evidence:
file:human/TSG101/TSG101-uniprot.txt
Component of the ESCRT-I complex
file:human/TSG101/TSG101-uniprot.txt
Binds to ubiquitinated cargo proteins
file:human/TSG101/TSG101-uniprot.txt
required for the sorting of endocytic ubiquitinated cargos into
file:human/TSG101/TSG101-uniprot.txt
which consists of TSG101, VPS28, a VPS37 protein
PMID:12900395
ESCRT-I subunit Tsg101
PMID:12900395
the initial recruitment of ESCRT-I to endosomes
file:human/TSG101/TSG101-uniprot.txt
Binds to ubiquitinated cargo proteins
file:human/TSG101/TSG101-uniprot.txt
Interacts with ubiquitin
GO:0016236 macroautophagy
TAS
PMID:20588296
Membrane budding and scission by the ESCRT machinery: it's a...
MODIFY
Summary: macroautophagy is too broad or late-fusion-biased for the TSG101 autophagy role.
Reason: The best-supported PN autophagy interpretation is ESCRT-I-mediated phagophore/autophagosome closure, which is better represented by autophagosome assembly.
Proposed replacements: autophagosome assembly
Supporting Evidence:
PMID:31519728
VPS37A directs ESCRT recruitment for phagophore closure
PMID:31519728
the core ESCRT-I components TSG101 and VPS28
PMID:31519728
required for autophagosome completion
PMID:31519728
phagophore closure in mammalian cells
PMID:31010855
mediates AP sealing
PMID:31010855
ESCRT catalyzes AP closure
GO:0042059 negative regulation of epidermal growth factor receptor signaling pathway
IMP
PMID:16554368
The ESCRT-III subunit hVps24 is required for degradation but...
ACCEPT
Summary: negative regulation of epidermal growth factor receptor signaling pathway is supported as a cargo-sorting consequence of ESCRT-I function.
Reason: TSG101-mediated ESCRT-I sorting of ubiquitinated receptors into the MVB/lysosomal pathway explains EGFR/endocytosis down-regulation annotations.
Supporting Evidence:
file:human/TSG101/TSG101-uniprot.txt
required for the sorting of endocytic ubiquitinated cargos into
file:human/TSG101/TSG101-uniprot.txt
multivesicular bodies
PMID:12900395
indirectly regulates multivesicular body formation
PMID:12900395
the initial recruitment of ESCRT-I to endosomes
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 TSG101 cellular-component annotation.
Reason: TSG101 is a stoichiometric core ESCRT-I subunit with VPS28, VPS37-family subunits, and MVB12/UBAP-family subunits.
Supporting Evidence:
file:human/TSG101/TSG101-uniprot.txt
Component of the ESCRT-I complex
file:human/TSG101/TSG101-uniprot.txt
Binds to ubiquitinated cargo proteins
file:human/TSG101/TSG101-uniprot.txt
required for the sorting of endocytic ubiquitinated cargos into
file:human/TSG101/TSG101-uniprot.txt
which consists of TSG101, VPS28, a VPS37 protein
PMID:12900395
ESCRT-I subunit Tsg101
PMID:12900395
the initial recruitment of ESCRT-I to endosomes
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: TSG101/ESCRT-I sorts ubiquitinated endocytic cargo into MVBs and thereby supports endosome-to-lysosome/vacuolar delivery of cargo.
Supporting Evidence:
file:human/TSG101/TSG101-uniprot.txt
required for the sorting of endocytic ubiquitinated cargos into
file:human/TSG101/TSG101-uniprot.txt
multivesicular bodies
PMID:12900395
indirectly regulates multivesicular body formation
PMID:12900395
the initial recruitment of ESCRT-I to endosomes
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 but reflects host-pathogen exploitation of ESCRT-I.
Reason: Viral budding/release annotations are well supported for TSG101 but are non-core for the human proteostasis-network review.
Supporting Evidence:
file:human/TSG101/TSG101-uniprot.txt
Involved in the budding of many viruses
file:human/TSG101/TSG101-uniprot.txt
interaction is essential for viral particle budding
PMID:11595185
required for HIV-1 budding
PMID:11595185
arrests HIV-1 budding at a late stage
GO:0000813 ESCRT I complex
TAS
PMID:21118109
The role of ESCRT proteins in fusion events involving lysoso...
ACCEPT
Summary: ESCRT-I complex membership is the central TSG101 cellular-component annotation.
Reason: TSG101 is a stoichiometric core ESCRT-I subunit with VPS28, VPS37-family subunits, and MVB12/UBAP-family subunits.
Supporting Evidence:
file:human/TSG101/TSG101-uniprot.txt
Component of the ESCRT-I complex
file:human/TSG101/TSG101-uniprot.txt
Binds to ubiquitinated cargo proteins
file:human/TSG101/TSG101-uniprot.txt
required for the sorting of endocytic ubiquitinated cargos into
file:human/TSG101/TSG101-uniprot.txt
which consists of TSG101, VPS28, a VPS37 protein
PMID:12900395
ESCRT-I subunit Tsg101
PMID:12900395
the initial recruitment of ESCRT-I to endosomes
GO:0097352 autophagosome maturation
TAS
PMID:21118109
The role of ESCRT proteins in fusion events involving lysoso...
MODIFY
Summary: autophagosome maturation is too broad or late-fusion-biased for the TSG101 autophagy role.
Reason: The best-supported PN autophagy interpretation is ESCRT-I-mediated phagophore/autophagosome closure, which is better represented by autophagosome assembly.
Proposed replacements: autophagosome assembly
Supporting Evidence:
PMID:31519728
VPS37A directs ESCRT recruitment for phagophore closure
PMID:31519728
the core ESCRT-I components TSG101 and VPS28
PMID:31519728
required for autophagosome completion
PMID:31519728
phagophore closure in mammalian cells
PMID:31010855
mediates AP sealing
PMID:31010855
ESCRT catalyzes AP closure
GO:0043405 regulation of MAP kinase activity
IMP
PMID:17714434
Vps22/EAP30 in ESCRT-II mediates endosomal sorting of growth...
KEEP AS NON CORE
Summary: MAP kinase regulation is a downstream receptor-signaling consequence and not core.
Reason: This likely reflects altered EGFR trafficking/signaling downstream of ESCRT function rather than a direct TSG101 molecular role.
Supporting Evidence:
file:human/TSG101/TSG101-uniprot.txt
required for the sorting of endocytic ubiquitinated cargos into
file:human/TSG101/TSG101-uniprot.txt
multivesicular bodies
PMID:12900395
indirectly regulates multivesicular body formation
PMID:12900395
the initial recruitment of ESCRT-I to endosomes
GO:0005515 protein binding
IPI
PMID:16973552
Human ESCRT-II complex and its role in human immunodeficienc...
MARK AS OVER ANNOTATED
Summary: protein binding is too generic to represent TSG101 function.
Reason: The interaction evidence should be represented by ubiquitin binding, ESCRT-I complex membership, MVB sorting, viral budding context, or cytokinesis context rather than generic binding terms.
Supporting Evidence:
file:human/TSG101/TSG101-uniprot.txt
Component of the ESCRT-I complex
file:human/TSG101/TSG101-uniprot.txt
Binds to ubiquitinated cargo proteins
file:human/TSG101/TSG101-uniprot.txt
required for the sorting of endocytic ubiquitinated cargos into
file:human/TSG101/TSG101-uniprot.txt
which consists of TSG101, VPS28, a VPS37 protein
PMID:12900395
ESCRT-I subunit Tsg101
PMID:12900395
the initial recruitment of ESCRT-I to endosomes
file:human/TSG101/TSG101-uniprot.txt
Binds to ubiquitinated cargo proteins
file:human/TSG101/TSG101-uniprot.txt
Interacts with ubiquitin
GO:0019076 viral release from host cell
IMP
PMID:11595185
Tsg101 and the vacuolar protein sorting pathway are essentia...
KEEP AS NON CORE
Summary: viral release from host cell is supported but reflects host-pathogen exploitation of ESCRT-I.
Reason: Viral budding/release annotations are well supported for TSG101 but are non-core for the human proteostasis-network review.
Supporting Evidence:
file:human/TSG101/TSG101-uniprot.txt
Involved in the budding of many viruses
file:human/TSG101/TSG101-uniprot.txt
interaction is essential for viral particle budding
PMID:11595185
required for HIV-1 budding
PMID:11595185
arrests HIV-1 budding at a late stage
GO:0043130 ubiquitin binding
IDA
PMID:11595185
Tsg101 and the vacuolar protein sorting pathway are essentia...
ACCEPT
Summary: Ubiquitin binding is a core TSG101 UEV-domain molecular function.
Reason: TSG101 binds ubiquitin/ubiquitinated cargo through its UEV domain and uses that activity in ESCRT-I cargo sorting and PTAP-motif recruitment contexts.
Supporting Evidence:
file:human/TSG101/TSG101-uniprot.txt
Binds to ubiquitinated cargo proteins
file:human/TSG101/TSG101-uniprot.txt
Interacts with ubiquitin
file:human/TSG101/TSG101-uniprot.txt
The UEV domain binds ubiquitin
PMID:11595185
UEV domain of Tsg101 binds
PMID:11595185
to ubiquitin
GO:0046790 virion binding
IDA
PMID:11595185
Tsg101 and the vacuolar protein sorting pathway are essentia...
KEEP AS NON CORE
Summary: virion binding is supported but reflects host-pathogen exploitation of ESCRT-I.
Reason: Viral budding/release annotations are well supported for TSG101 but are non-core for the human proteostasis-network review.
Supporting Evidence:
file:human/TSG101/TSG101-uniprot.txt
Involved in the budding of many viruses
file:human/TSG101/TSG101-uniprot.txt
interaction is essential for viral particle budding
PMID:11595185
required for HIV-1 budding
PMID:11595185
arrests HIV-1 budding at a late stage
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 TSG101 cellular-component annotation.
Reason: TSG101 is a stoichiometric core ESCRT-I subunit with VPS28, VPS37-family subunits, and MVB12/UBAP-family subunits.
Supporting Evidence:
file:human/TSG101/TSG101-uniprot.txt
Component of the ESCRT-I complex
file:human/TSG101/TSG101-uniprot.txt
Binds to ubiquitinated cargo proteins
file:human/TSG101/TSG101-uniprot.txt
required for the sorting of endocytic ubiquitinated cargos into
file:human/TSG101/TSG101-uniprot.txt
which consists of TSG101, VPS28, a VPS37 protein
PMID:12900395
ESCRT-I subunit Tsg101
PMID:12900395
the initial recruitment of ESCRT-I to endosomes
GO:0005768 endosome
IDA
PMID:17940959
Involvement of vacuolar protein sorting pathway in Ebola vir...
ACCEPT
Summary: endosome localization is supported and relevant to ESCRT-I cargo sorting.
Reason: TSG101 cycles between cytosol and active endosomal membranes, including early/late endosome and MVB contexts where ESCRT-I functions.
Supporting Evidence:
file:human/TSG101/TSG101-uniprot.txt
Early endosome membrane
file:human/TSG101/TSG101-uniprot.txt
Late endosome membrane
PMID:12900395
Tsg101 to late endosomes
PMID:12900395
colocalize on a subpopulation of endosomes
GO:0005886 plasma membrane
IDA
PMID:17940959
Involvement of vacuolar protein sorting pathway in Ebola vir...
KEEP AS NON CORE
Summary: plasma membrane localization is supported but is not the core proteostasis annotation.
Reason: These locations reflect broad cytosolic/nuclear/midbody/plasma-membrane contexts for TSG101 and ESCRT-associated functions, but the core review focus is ESCRT-I endosomal sorting and phagophore closure.
Supporting Evidence:
file:human/TSG101/TSG101-uniprot.txt
Mainly cytoplasmic
file:human/TSG101/TSG101-uniprot.txt
Nuclear localization is cell cycle-dependent
file:human/TSG101/TSG101-uniprot.txt
localization to the midbody during cytokinesis
GO:1903774 positive regulation of viral budding via host ESCRT complex
IMP
PMID:15218037
The human endosomal sorting complex required for transport (...
KEEP AS NON CORE
Summary: positive regulation of viral budding via host ESCRT complex is supported but reflects host-pathogen exploitation of ESCRT-I.
Reason: Viral budding/release annotations are well supported for TSG101 but are non-core for the human proteostasis-network review.
Supporting Evidence:
file:human/TSG101/TSG101-uniprot.txt
Involved in the budding of many viruses
file:human/TSG101/TSG101-uniprot.txt
interaction is essential for viral particle budding
PMID:11595185
required for HIV-1 budding
PMID:11595185
arrests HIV-1 budding at a late stage
GO:0019076 viral release from host cell
IMP
PMID:15218037
The human endosomal sorting complex required for transport (...
KEEP AS NON CORE
Summary: viral release from host cell is supported but reflects host-pathogen exploitation of ESCRT-I.
Reason: Viral budding/release annotations are well supported for TSG101 but are non-core for the human proteostasis-network review.
Supporting Evidence:
file:human/TSG101/TSG101-uniprot.txt
Involved in the budding of many viruses
file:human/TSG101/TSG101-uniprot.txt
interaction is essential for viral particle budding
PMID:11595185
required for HIV-1 budding
PMID:11595185
arrests HIV-1 budding at a late stage
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 ESCRT-I cargo sorting.
Reason: TSG101 cycles between cytosol and active endosomal membranes, including early/late endosome and MVB contexts where ESCRT-I functions.
Supporting Evidence:
file:human/TSG101/TSG101-uniprot.txt
Early endosome membrane
file:human/TSG101/TSG101-uniprot.txt
Late endosome membrane
PMID:12900395
Tsg101 to late endosomes
PMID:12900395
colocalize on a subpopulation of endosomes
GO:0043130 ubiquitin binding
IDA
PMID:11916981
Mammalian class E vps proteins recognize ubiquitin and act i...
ACCEPT
Summary: Ubiquitin binding is a core TSG101 UEV-domain molecular function.
Reason: TSG101 binds ubiquitin/ubiquitinated cargo through its UEV domain and uses that activity in ESCRT-I cargo sorting and PTAP-motif recruitment contexts.
Supporting Evidence:
file:human/TSG101/TSG101-uniprot.txt
Binds to ubiquitinated cargo proteins
file:human/TSG101/TSG101-uniprot.txt
Interacts with ubiquitin
file:human/TSG101/TSG101-uniprot.txt
The UEV domain binds ubiquitin
PMID:11595185
UEV domain of Tsg101 binds
PMID:11595185
to ubiquitin
GO:1903551 regulation of extracellular exosome assembly
IMP
PMID:24105262
Analysis of ESCRT functions in exosome biogenesis, compositi...
KEEP AS NON CORE
Summary: regulation of extracellular exosome assembly is supported but non-core in this PN review.
Reason: TSG101 contributes to exosome/microvesicle release, but the proteostasis core here is ESCRT-I endosomal cargo sorting and autophagophore closure.
Supporting Evidence:
file:human/TSG101/TSG101-uniprot.txt
Required for the exosomal release of SDCBP, CD63 and syndecan
file:human/TSG101/TSG101-uniprot.txt
extracellular release of microvesicles
GO:1903543 positive regulation of exosomal secretion
IMP
PMID:22660413
Syndecan-syntenin-ALIX regulates the biogenesis of exosomes.
KEEP AS NON CORE
Summary: positive regulation of exosomal secretion is supported but non-core in this PN review.
Reason: TSG101 contributes to exosome/microvesicle release, but the proteostasis core here is ESCRT-I endosomal cargo sorting and autophagophore closure.
Supporting Evidence:
file:human/TSG101/TSG101-uniprot.txt
Required for the exosomal release of SDCBP, CD63 and syndecan
file:human/TSG101/TSG101-uniprot.txt
extracellular release of microvesicles
GO:1903543 positive regulation of exosomal secretion
IMP
PMID:24105262
Analysis of ESCRT functions in exosome biogenesis, compositi...
KEEP AS NON CORE
Summary: positive regulation of exosomal secretion is supported but non-core in this PN review.
Reason: TSG101 contributes to exosome/microvesicle release, but the proteostasis core here is ESCRT-I endosomal cargo sorting and autophagophore closure.
Supporting Evidence:
file:human/TSG101/TSG101-uniprot.txt
Required for the exosomal release of SDCBP, CD63 and syndecan
file:human/TSG101/TSG101-uniprot.txt
extracellular release of microvesicles
GO:0070062 extracellular exosome
IDA
PMID:23092844
Monitoring the Rab27 associated exosome pathway using nanopa...
KEEP AS NON CORE
Summary: Extracellular exosome detection is supported but is a non-core localization/context.
Reason: TSG101 is commonly detected in exosome preparations and regulates exosomal release, but this is secondary to its ESCRT-I membrane-remodeling role.
Supporting Evidence:
file:human/TSG101/TSG101-uniprot.txt
Required for the exosomal release of SDCBP, CD63 and syndecan
file:human/TSG101/TSG101-uniprot.txt
extracellular release of microvesicles
GO:0070062 extracellular exosome
HDA
PMID:23533145
In-depth proteomic analyses of exosomes isolated from expres...
KEEP AS NON CORE
Summary: Extracellular exosome detection is supported but is a non-core localization/context.
Reason: TSG101 is commonly detected in exosome preparations and regulates exosomal release, but this is secondary to its ESCRT-I membrane-remodeling role.
Supporting Evidence:
file:human/TSG101/TSG101-uniprot.txt
Required for the exosomal release of SDCBP, CD63 and syndecan
file:human/TSG101/TSG101-uniprot.txt
extracellular release of microvesicles
GO:0070062 extracellular exosome
IDA
PMID:16501490
Collection, storage, preservation, and normalization of huma...
KEEP AS NON CORE
Summary: Extracellular exosome detection is supported but is a non-core localization/context.
Reason: TSG101 is commonly detected in exosome preparations and regulates exosomal release, but this is secondary to its ESCRT-I membrane-remodeling role.
Supporting Evidence:
file:human/TSG101/TSG101-uniprot.txt
Required for the exosomal release of SDCBP, CD63 and syndecan
file:human/TSG101/TSG101-uniprot.txt
extracellular release of microvesicles
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 TSG101 function.
Reason: The interaction evidence should be represented by ubiquitin binding, ESCRT-I complex membership, MVB sorting, viral budding context, or cytokinesis context rather than generic binding terms.
Supporting Evidence:
file:human/TSG101/TSG101-uniprot.txt
Component of the ESCRT-I complex
file:human/TSG101/TSG101-uniprot.txt
Binds to ubiquitinated cargo proteins
file:human/TSG101/TSG101-uniprot.txt
required for the sorting of endocytic ubiquitinated cargos into
file:human/TSG101/TSG101-uniprot.txt
which consists of TSG101, VPS28, a VPS37 protein
PMID:12900395
ESCRT-I subunit Tsg101
PMID:12900395
the initial recruitment of ESCRT-I to endosomes
file:human/TSG101/TSG101-uniprot.txt
Binds to ubiquitinated cargo proteins
file:human/TSG101/TSG101-uniprot.txt
Interacts with ubiquitin
GO:0042803 protein homodimerization activity
IPI
PMID:14519844
Divergent retroviral late-budding domains recruit vacuolar p...
KEEP AS NON CORE
Summary: Homodimerization is supported as a structural interaction but is not the core functional annotation.
Reason: Retain this as a non-core interaction property; ESCRT-I complex membership and ubiquitin binding capture the main TSG101 role.
Supporting Evidence:
file:human/TSG101/TSG101-uniprot.txt
Self-associates
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 TSG101 function.
Reason: The interaction evidence should be represented by ubiquitin binding, ESCRT-I complex membership, MVB sorting, viral budding context, or cytokinesis context rather than generic binding terms.
Supporting Evidence:
file:human/TSG101/TSG101-uniprot.txt
Component of the ESCRT-I complex
file:human/TSG101/TSG101-uniprot.txt
Binds to ubiquitinated cargo proteins
file:human/TSG101/TSG101-uniprot.txt
required for the sorting of endocytic ubiquitinated cargos into
file:human/TSG101/TSG101-uniprot.txt
which consists of TSG101, VPS28, a VPS37 protein
PMID:12900395
ESCRT-I subunit Tsg101
PMID:12900395
the initial recruitment of ESCRT-I to endosomes
file:human/TSG101/TSG101-uniprot.txt
Binds to ubiquitinated cargo proteins
file:human/TSG101/TSG101-uniprot.txt
Interacts with ubiquitin
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 TSG101 cellular-component annotation.
Reason: TSG101 is a stoichiometric core ESCRT-I subunit with VPS28, VPS37-family subunits, and MVB12/UBAP-family subunits.
Supporting Evidence:
file:human/TSG101/TSG101-uniprot.txt
Component of the ESCRT-I complex
file:human/TSG101/TSG101-uniprot.txt
Binds to ubiquitinated cargo proteins
file:human/TSG101/TSG101-uniprot.txt
required for the sorting of endocytic ubiquitinated cargos into
file:human/TSG101/TSG101-uniprot.txt
which consists of TSG101, VPS28, a VPS37 protein
PMID:12900395
ESCRT-I subunit Tsg101
PMID:12900395
the initial recruitment of ESCRT-I to endosomes
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 TSG101 cellular-component annotation.
Reason: TSG101 is a stoichiometric core ESCRT-I subunit with VPS28, VPS37-family subunits, and MVB12/UBAP-family subunits.
Supporting Evidence:
file:human/TSG101/TSG101-uniprot.txt
Component of the ESCRT-I complex
file:human/TSG101/TSG101-uniprot.txt
Binds to ubiquitinated cargo proteins
file:human/TSG101/TSG101-uniprot.txt
required for the sorting of endocytic ubiquitinated cargos into
file:human/TSG101/TSG101-uniprot.txt
which consists of TSG101, VPS28, a VPS37 protein
PMID:12900395
ESCRT-I subunit Tsg101
PMID:12900395
the initial recruitment of ESCRT-I to endosomes
GO:0043130 ubiquitin binding
IDA
PMID:20654576
Distinct functions of human MVB12A and MVB12B in the ESCRT-I...
ACCEPT
Summary: Ubiquitin binding is a core TSG101 UEV-domain molecular function.
Reason: TSG101 binds ubiquitin/ubiquitinated cargo through its UEV domain and uses that activity in ESCRT-I cargo sorting and PTAP-motif recruitment contexts.
Supporting Evidence:
file:human/TSG101/TSG101-uniprot.txt
Binds to ubiquitinated cargo proteins
file:human/TSG101/TSG101-uniprot.txt
Interacts with ubiquitin
file:human/TSG101/TSG101-uniprot.txt
The UEV domain binds ubiquitin
PMID:11595185
UEV domain of Tsg101 binds
PMID:11595185
to ubiquitin
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: TSG101/ESCRT-I sorts ubiquitinated endocytic cargo into MVBs and thereby supports endosome-to-lysosome/vacuolar delivery of cargo.
Supporting Evidence:
file:human/TSG101/TSG101-uniprot.txt
required for the sorting of endocytic ubiquitinated cargos into
file:human/TSG101/TSG101-uniprot.txt
multivesicular bodies
PMID:12900395
indirectly regulates multivesicular body formation
PMID:12900395
the initial recruitment of ESCRT-I to endosomes
GO:0070062 extracellular exosome
HDA
PMID:19056867
Large-scale proteomics and phosphoproteomics of urinary exos...
KEEP AS NON CORE
Summary: Extracellular exosome detection is supported but is a non-core localization/context.
Reason: TSG101 is commonly detected in exosome preparations and regulates exosomal release, but this is secondary to its ESCRT-I membrane-remodeling role.
Supporting Evidence:
file:human/TSG101/TSG101-uniprot.txt
Required for the exosomal release of SDCBP, CD63 and syndecan
file:human/TSG101/TSG101-uniprot.txt
extracellular release of microvesicles
GO:0010008 endosome membrane
TAS
Reactome:R-HSA-184269
ACCEPT
Summary: endosome membrane localization is supported and relevant to ESCRT-I cargo sorting.
Reason: TSG101 cycles between cytosol and active endosomal membranes, including early/late endosome and MVB contexts where ESCRT-I functions.
Supporting Evidence:
file:human/TSG101/TSG101-uniprot.txt
Early endosome membrane
file:human/TSG101/TSG101-uniprot.txt
Late endosome membrane
PMID:12900395
Tsg101 to late endosomes
PMID:12900395
colocalize on a subpopulation of endosomes
GO:0010008 endosome membrane
TAS
Reactome:R-HSA-3149434
ACCEPT
Summary: endosome membrane localization is supported and relevant to ESCRT-I cargo sorting.
Reason: TSG101 cycles between cytosol and active endosomal membranes, including early/late endosome and MVB contexts where ESCRT-I functions.
Supporting Evidence:
file:human/TSG101/TSG101-uniprot.txt
Early endosome membrane
file:human/TSG101/TSG101-uniprot.txt
Late endosome membrane
PMID:12900395
Tsg101 to late endosomes
PMID:12900395
colocalize on a subpopulation of endosomes
GO:0010008 endosome membrane
TAS
Reactome:R-HSA-3159232
ACCEPT
Summary: endosome membrane localization is supported and relevant to ESCRT-I cargo sorting.
Reason: TSG101 cycles between cytosol and active endosomal membranes, including early/late endosome and MVB contexts where ESCRT-I functions.
Supporting Evidence:
file:human/TSG101/TSG101-uniprot.txt
Early endosome membrane
file:human/TSG101/TSG101-uniprot.txt
Late endosome membrane
PMID:12900395
Tsg101 to late endosomes
PMID:12900395
colocalize on a subpopulation of endosomes
GO:0010008 endosome membrane
TAS
Reactome:R-HSA-917696
ACCEPT
Summary: endosome membrane localization is supported and relevant to ESCRT-I cargo sorting.
Reason: TSG101 cycles between cytosol and active endosomal membranes, including early/late endosome and MVB contexts where ESCRT-I functions.
Supporting Evidence:
file:human/TSG101/TSG101-uniprot.txt
Early endosome membrane
file:human/TSG101/TSG101-uniprot.txt
Late endosome membrane
PMID:12900395
Tsg101 to late endosomes
PMID:12900395
colocalize on a subpopulation of endosomes
GO:0010008 endosome membrane
TAS
Reactome:R-HSA-917730
ACCEPT
Summary: endosome membrane localization is supported and relevant to ESCRT-I cargo sorting.
Reason: TSG101 cycles between cytosol and active endosomal membranes, including early/late endosome and MVB contexts where ESCRT-I functions.
Supporting Evidence:
file:human/TSG101/TSG101-uniprot.txt
Early endosome membrane
file:human/TSG101/TSG101-uniprot.txt
Late endosome membrane
PMID:12900395
Tsg101 to late endosomes
PMID:12900395
colocalize on a subpopulation of endosomes
GO:0070062 extracellular exosome
IDA
PMID:15326289
Identification and proteomic profiling of exosomes in human ...
KEEP AS NON CORE
Summary: Extracellular exosome detection is supported but is a non-core localization/context.
Reason: TSG101 is commonly detected in exosome preparations and regulates exosomal release, but this is secondary to its ESCRT-I membrane-remodeling role.
Supporting Evidence:
file:human/TSG101/TSG101-uniprot.txt
Required for the exosomal release of SDCBP, CD63 and syndecan
file:human/TSG101/TSG101-uniprot.txt
extracellular release of microvesicles
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 TSG101 cellular-component annotation.
Reason: TSG101 is a stoichiometric core ESCRT-I subunit with VPS28, VPS37-family subunits, and MVB12/UBAP-family subunits.
Supporting Evidence:
file:human/TSG101/TSG101-uniprot.txt
Component of the ESCRT-I complex
file:human/TSG101/TSG101-uniprot.txt
Binds to ubiquitinated cargo proteins
file:human/TSG101/TSG101-uniprot.txt
required for the sorting of endocytic ubiquitinated cargos into
file:human/TSG101/TSG101-uniprot.txt
which consists of TSG101, VPS28, a VPS37 protein
PMID:12900395
ESCRT-I subunit Tsg101
PMID:12900395
the initial recruitment of ESCRT-I to endosomes
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: TSG101/ESCRT-I sorts ubiquitinated endocytic cargo into MVBs and thereby supports endosome-to-lysosome/vacuolar delivery of cargo.
Supporting Evidence:
file:human/TSG101/TSG101-uniprot.txt
required for the sorting of endocytic ubiquitinated cargos into
file:human/TSG101/TSG101-uniprot.txt
multivesicular bodies
PMID:12900395
indirectly regulates multivesicular body formation
PMID:12900395
the initial recruitment of ESCRT-I to endosomes
GO:0031625 ubiquitin protein ligase binding
IPI
PMID:17229889
Spongiform neurodegeneration-associated E3 ligase Mahogunin ...
KEEP AS NON CORE
Summary: Ubiquitin ligase binding is supported as regulatory context but not core.
Reason: TSG101 interacts with LRSAM1/MGRN1 and can be monoubiquitinated, but this regulatory binding is secondary to ESCRT-I cargo sorting.
Supporting Evidence:
file:human/TSG101/TSG101-uniprot.txt
Interacts with LRSAM1
file:human/TSG101/TSG101-uniprot.txt
Interacts with MGRN1
file:human/TSG101/TSG101-uniprot.txt
Monoubiquitinated at multiple sites by LRSAM1 and by MGRN1
GO:0005769 early endosome
IDA
PMID:17229889
Spongiform neurodegeneration-associated E3 ligase Mahogunin ...
ACCEPT
Summary: early endosome localization is supported and relevant to ESCRT-I cargo sorting.
Reason: TSG101 cycles between cytosol and active endosomal membranes, including early/late endosome and MVB contexts where ESCRT-I functions.
Supporting Evidence:
file:human/TSG101/TSG101-uniprot.txt
Early endosome membrane
file:human/TSG101/TSG101-uniprot.txt
Late endosome membrane
PMID:12900395
Tsg101 to late endosomes
PMID:12900395
colocalize on a subpopulation of endosomes
GO:0005515 protein binding
IPI
PMID:18256029
Identification of Alix-type and Non-Alix-type ALG-2-binding ...
MARK AS OVER ANNOTATED
Summary: protein binding is too generic to represent TSG101 function.
Reason: The interaction evidence should be represented by ubiquitin binding, ESCRT-I complex membership, MVB sorting, viral budding context, or cytokinesis context rather than generic binding terms.
Supporting Evidence:
file:human/TSG101/TSG101-uniprot.txt
Component of the ESCRT-I complex
file:human/TSG101/TSG101-uniprot.txt
Binds to ubiquitinated cargo proteins
file:human/TSG101/TSG101-uniprot.txt
required for the sorting of endocytic ubiquitinated cargos into
file:human/TSG101/TSG101-uniprot.txt
which consists of TSG101, VPS28, a VPS37 protein
PMID:12900395
ESCRT-I subunit Tsg101
PMID:12900395
the initial recruitment of ESCRT-I to endosomes
file:human/TSG101/TSG101-uniprot.txt
Binds to ubiquitinated cargo proteins
file:human/TSG101/TSG101-uniprot.txt
Interacts with ubiquitin
GO:0048306 calcium-dependent protein binding
IPI
PMID:19520058
Penta-EF-hand protein ALG-2 functions as a Ca2+-dependent ad...
MARK AS OVER ANNOTATED
Summary: calcium-dependent protein binding is too generic to represent TSG101 function.
Reason: The interaction evidence should be represented by ubiquitin binding, ESCRT-I complex membership, MVB sorting, viral budding context, or cytokinesis context rather than generic binding terms.
Supporting Evidence:
file:human/TSG101/TSG101-uniprot.txt
Component of the ESCRT-I complex
file:human/TSG101/TSG101-uniprot.txt
Binds to ubiquitinated cargo proteins
file:human/TSG101/TSG101-uniprot.txt
required for the sorting of endocytic ubiquitinated cargos into
file:human/TSG101/TSG101-uniprot.txt
which consists of TSG101, VPS28, a VPS37 protein
PMID:12900395
ESCRT-I subunit Tsg101
PMID:12900395
the initial recruitment of ESCRT-I to endosomes
file:human/TSG101/TSG101-uniprot.txt
Binds to ubiquitinated cargo proteins
file:human/TSG101/TSG101-uniprot.txt
Interacts with ubiquitin
GO:0005515 protein binding
IPI
PMID:18077552
Regulation of Tsg101 expression by the steadiness box: a rol...
MARK AS OVER ANNOTATED
Summary: protein binding is too generic to represent TSG101 function.
Reason: The interaction evidence should be represented by ubiquitin binding, ESCRT-I complex membership, MVB sorting, viral budding context, or cytokinesis context rather than generic binding terms.
Supporting Evidence:
file:human/TSG101/TSG101-uniprot.txt
Component of the ESCRT-I complex
file:human/TSG101/TSG101-uniprot.txt
Binds to ubiquitinated cargo proteins
file:human/TSG101/TSG101-uniprot.txt
required for the sorting of endocytic ubiquitinated cargos into
file:human/TSG101/TSG101-uniprot.txt
which consists of TSG101, VPS28, a VPS37 protein
PMID:12900395
ESCRT-I subunit Tsg101
PMID:12900395
the initial recruitment of ESCRT-I to endosomes
file:human/TSG101/TSG101-uniprot.txt
Binds to ubiquitinated cargo proteins
file:human/TSG101/TSG101-uniprot.txt
Interacts with ubiquitin
GO:0005737 cytoplasm
ISS
GO_REF:0000024
KEEP AS NON CORE
Summary: cytoplasm localization is supported but is not the core proteostasis annotation.
Reason: These locations reflect broad cytosolic/nuclear/midbody/plasma-membrane contexts for TSG101 and ESCRT-associated functions, but the core review focus is ESCRT-I endosomal sorting and phagophore closure.
Supporting Evidence:
file:human/TSG101/TSG101-uniprot.txt
Mainly cytoplasmic
file:human/TSG101/TSG101-uniprot.txt
Nuclear localization is cell cycle-dependent
file:human/TSG101/TSG101-uniprot.txt
localization to the midbody during cytokinesis
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 is not the core proteostasis annotation.
Reason: These locations reflect broad cytosolic/nuclear/midbody/plasma-membrane contexts for TSG101 and ESCRT-associated functions, but the core review focus is ESCRT-I endosomal sorting and phagophore closure.
Supporting Evidence:
file:human/TSG101/TSG101-uniprot.txt
Mainly cytoplasmic
file:human/TSG101/TSG101-uniprot.txt
Nuclear localization is cell cycle-dependent
file:human/TSG101/TSG101-uniprot.txt
localization to the midbody during cytokinesis
GO:0046755 viral budding
ISS
GO_REF:0000024
KEEP AS NON CORE
Summary: viral budding is supported but reflects host-pathogen exploitation of ESCRT-I.
Reason: Viral budding/release annotations are well supported for TSG101 but are non-core for the human proteostasis-network review.
Supporting Evidence:
file:human/TSG101/TSG101-uniprot.txt
Involved in the budding of many viruses
file:human/TSG101/TSG101-uniprot.txt
interaction is essential for viral particle budding
PMID:11595185
required for HIV-1 budding
PMID:11595185
arrests HIV-1 budding at a late stage
GO:0005770 late endosome
IMP
PMID:15126635
Nedd4.1-mediated ubiquitination and subsequent recruitment o...
ACCEPT
Summary: late endosome localization is supported and relevant to ESCRT-I cargo sorting.
Reason: TSG101 cycles between cytosol and active endosomal membranes, including early/late endosome and MVB contexts where ESCRT-I functions.
Supporting Evidence:
file:human/TSG101/TSG101-uniprot.txt
Early endosome membrane
file:human/TSG101/TSG101-uniprot.txt
Late endosome membrane
PMID:12900395
Tsg101 to late endosomes
PMID:12900395
colocalize on a subpopulation of endosomes
GO:0046755 viral budding
IMP
PMID:15126635
Nedd4.1-mediated ubiquitination and subsequent recruitment o...
KEEP AS NON CORE
Summary: viral budding is supported but reflects host-pathogen exploitation of ESCRT-I.
Reason: Viral budding/release annotations are well supported for TSG101 but are non-core for the human proteostasis-network review.
Supporting Evidence:
file:human/TSG101/TSG101-uniprot.txt
Involved in the budding of many viruses
file:human/TSG101/TSG101-uniprot.txt
interaction is essential for viral particle budding
PMID:11595185
required for HIV-1 budding
PMID:11595185
arrests HIV-1 budding at a late stage
GO:0005771 multivesicular body
TAS
PMID:15611048
Interactions of TOM1L1 with the multivesicular body sorting ...
ACCEPT
Summary: multivesicular body localization is supported and relevant to ESCRT-I cargo sorting.
Reason: TSG101 cycles between cytosol and active endosomal membranes, including early/late endosome and MVB contexts where ESCRT-I functions.
Supporting Evidence:
file:human/TSG101/TSG101-uniprot.txt
Early endosome membrane
file:human/TSG101/TSG101-uniprot.txt
Late endosome membrane
PMID:12900395
Tsg101 to late endosomes
PMID:12900395
colocalize on a subpopulation of endosomes
GO:0043130 ubiquitin binding
TAS
PMID:15611048
Interactions of TOM1L1 with the multivesicular body sorting ...
ACCEPT
Summary: Ubiquitin binding is a core TSG101 UEV-domain molecular function.
Reason: TSG101 binds ubiquitin/ubiquitinated cargo through its UEV domain and uses that activity in ESCRT-I cargo sorting and PTAP-motif recruitment contexts.
Supporting Evidence:
file:human/TSG101/TSG101-uniprot.txt
Binds to ubiquitinated cargo proteins
file:human/TSG101/TSG101-uniprot.txt
Interacts with ubiquitin
file:human/TSG101/TSG101-uniprot.txt
The UEV domain binds ubiquitin
PMID:11595185
UEV domain of Tsg101 binds
PMID:11595185
to ubiquitin
GO:0043162 ubiquitin-dependent protein catabolic process via the multivesicular body sorting pathway
IDA
PMID:15611048
Interactions of TOM1L1 with the multivesicular body sorting ...
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: TSG101/ESCRT-I sorts ubiquitinated endocytic cargo into MVBs and thereby supports endosome-to-lysosome/vacuolar delivery of cargo.
Supporting Evidence:
file:human/TSG101/TSG101-uniprot.txt
required for the sorting of endocytic ubiquitinated cargos into
file:human/TSG101/TSG101-uniprot.txt
multivesicular bodies
PMID:12900395
indirectly regulates multivesicular body formation
PMID:12900395
the initial recruitment of ESCRT-I to endosomes
GO:0003677 DNA binding
TAS
PMID:10888872
DNMT1 binds HDAC2 and a new co-repressor, DMAP1, to form a c...
MARK AS OVER ANNOTATED
Summary: DNA binding is a legacy/non-core nuclear transcription annotation and likely overstates the current functional picture.
Reason: The synthesized evidence supports ESCRT-I ubiquitin/cargo sorting and membrane scission; DNA/transcription terms are not central and are not well integrated with the current proteostasis review.
Supporting Evidence:
file:human/TSG101/TSG101-uniprot.txt
May be involved in cell growth and differentiation
file:human/TSG101/TSG101-uniprot.txt
Acts as a negative growth regulator
GO:0003714 transcription corepressor activity
TAS
PMID:10888872
DNMT1 binds HDAC2 and a new co-repressor, DMAP1, to form a c...
MARK AS OVER ANNOTATED
Summary: transcription corepressor activity is a legacy/non-core nuclear transcription annotation and likely overstates the current functional picture.
Reason: The synthesized evidence supports ESCRT-I ubiquitin/cargo sorting and membrane scission; DNA/transcription terms are not central and are not well integrated with the current proteostasis review.
Supporting Evidence:
file:human/TSG101/TSG101-uniprot.txt
May be involved in cell growth and differentiation
file:human/TSG101/TSG101-uniprot.txt
Acts as a negative growth regulator
GO:0000045 autophagosome assembly
IMP
PMID:31519728
VPS37A directs ESCRT recruitment for phagophore closure.
NEW
Summary: TSG101 should be added to autophagosome assembly for the ESCRT-I phagophore-closure role.
Reason: The PN leaf is autophagophore sealing, and mammalian evidence shows core ESCRT-I components including TSG101 are required for autophagosome completion/phagophore closure.
Supporting Evidence:
PMID:31519728
VPS37A directs ESCRT recruitment for phagophore closure
PMID:31519728
the core ESCRT-I components TSG101 and VPS28
PMID:31519728
required for autophagosome completion
PMID:31519728
phagophore closure in mammalian cells
PMID:31010855
mediates AP sealing
PMID:31010855
ESCRT catalyzes AP closure

Core Functions

TSG101 is the UEV-domain ESCRT-I adaptor/scaffold that binds ubiquitin/PTAP-type motifs and organizes ESCRT-I for ubiquitinated endocytic cargo sorting, MVB membrane remodeling, and ESCRT-dependent phagophore/autophagosome closure.

Supporting Evidence:
  • file:human/TSG101/TSG101-uniprot.txt
    Component of the ESCRT-I complex
  • file:human/TSG101/TSG101-uniprot.txt
    Binds to ubiquitinated cargo proteins
  • file:human/TSG101/TSG101-uniprot.txt
    required for the sorting of endocytic ubiquitinated cargos into
  • file:human/TSG101/TSG101-uniprot.txt
    which consists of TSG101, VPS28, a VPS37 protein
  • PMID:12900395
    ESCRT-I subunit Tsg101
  • PMID:12900395
    the initial recruitment of ESCRT-I to endosomes
  • file:human/TSG101/TSG101-uniprot.txt
    Binds to ubiquitinated cargo proteins
  • file:human/TSG101/TSG101-uniprot.txt
    Interacts with ubiquitin
  • file:human/TSG101/TSG101-uniprot.txt
    The UEV domain binds ubiquitin
  • PMID:11595185
    UEV domain of Tsg101 binds
  • PMID:11595185
    to ubiquitin
  • file:human/TSG101/TSG101-uniprot.txt
    required for the sorting of endocytic ubiquitinated cargos into
  • file:human/TSG101/TSG101-uniprot.txt
    multivesicular bodies
  • PMID:12900395
    indirectly regulates multivesicular body formation
  • PMID:12900395
    the initial recruitment of ESCRT-I to endosomes
  • PMID:31519728
    VPS37A directs ESCRT recruitment for phagophore closure
  • PMID:31519728
    the core ESCRT-I components TSG101 and VPS28
  • PMID:31519728
    required for autophagosome completion
  • PMID:31519728
    phagophore closure in mammalian cells
  • PMID:31010855
    mediates AP sealing
  • PMID:31010855
    ESCRT catalyzes AP closure

References

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Suggested Questions for Experts

Q: Should the TSG101 autophagy annotation be changed from broad macroautophagy/autophagosome maturation to GO:0000045 autophagosome assembly for phagophore closure?

Suggested experts: GO autophagy editors, GO ESCRT curators

Q: Should generic TSG101 protein-binding annotations be retired in favor of ubiquitin binding, ESCRT-I complex membership, and specific pathway contexts?

Suggested experts: GO molecular function editors, UniProt curators

Q: Should viral budding, cytokinesis, and exosome annotations remain non-core branches in proteostasis-focused TSG101 curation?

Suggested experts: GO viral process editors, GO cell-cycle editors, GO extracellular vesicle editors

Suggested Experiments

Experiment: Use acute TSG101 depletion/rescue with UEV-domain and VPS28/VPS37-binding mutants, then measure HT-LC3 closure, EGFR MVB sorting, and ESCRT-III/VPS4 recruitment side by side.

Hypothesis: TSG101 UEV-domain ubiquitin/PTAP-motif binding and ESCRT-I assembly surfaces make separable contributions to phagophore closure and MVB cargo sorting.

Type: TSG101 separation-of-function phagophore closure rescue

Experiment: Endogenously tag TSG101, VPS28, VPS37A, CHMP2A, and LC3 reporters and quantify recruitment order during starvation-induced phagophore closure.

Hypothesis: Core ESCRT-I components including TSG101 transiently localize to closing LC3-positive phagophores before ESCRT-III/VPS4 recruitment.

Type: endogenous ESCRT-I autophagy recruitment imaging

πŸ“š Additional Documentation

Notes

(TSG101-notes.md)

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Pn Notes

(TSG101-pn-notes.md)

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