id: Q99816
gene_symbol: TSG101
product_type: PROTEIN
status: COMPLETE
taxon:
  id: NCBITaxon:9606
  label: Homo sapiens
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.
alternative_products:
- name: '1'
  id: Q99816-1
- name: '2'
  id: Q99816-2
  sequence_note: VSP_004440
existing_annotations:
- term:
    id: GO:0000813
    label: ESCRT I complex
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: part_of
  review:
    summary: ESCRT-I complex membership is the central TSG101 cellular-component annotation.
    action: ACCEPT
    reason: TSG101 is a stoichiometric core ESCRT-I subunit with VPS28, VPS37-family subunits, and
      MVB12/UBAP-family subunits.
    additional_reference_ids: &id001
    - PMID:11595185
    - PMID:12900395
    - PMID:31519728
    - file:human/TSG101/TSG101-uniprot.txt
    - file:human/TSG101/TSG101-notes.md
    supported_by: &id002
    - &id006
      reference_id: file:human/TSG101/TSG101-uniprot.txt
      supporting_text: Component of the ESCRT-I complex
    - &id007
      reference_id: file:human/TSG101/TSG101-uniprot.txt
      supporting_text: Binds to ubiquitinated cargo proteins
    - &id008
      reference_id: file:human/TSG101/TSG101-uniprot.txt
      supporting_text: required for the sorting of endocytic ubiquitinated cargos into
    - &id009
      reference_id: file:human/TSG101/TSG101-uniprot.txt
      supporting_text: which consists of TSG101, VPS28, a VPS37 protein
    - &id010
      reference_id: PMID:12900395
      supporting_text: ESCRT-I subunit Tsg101
    - &id011
      reference_id: PMID:12900395
      supporting_text: the initial recruitment of ESCRT-I to endosomes
- term:
    id: GO:0008333
    label: endosome to lysosome transport
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: involved_in
  review:
    summary: endosome to lysosome transport is supported as part of the core ESCRT-I endosomal cargo-sorting
      role.
    action: ACCEPT
    reason: TSG101/ESCRT-I sorts ubiquitinated endocytic cargo into MVBs and thereby supports
      endosome-to-lysosome/vacuolar delivery of cargo.
    additional_reference_ids:
    - PMID:11595185
    - PMID:12900395
    - file:human/TSG101/TSG101-uniprot.txt
    - file:human/TSG101/TSG101-notes.md
    supported_by: &id004
    - &id025
      reference_id: file:human/TSG101/TSG101-uniprot.txt
      supporting_text: required for the sorting of endocytic ubiquitinated cargos into
    - &id026
      reference_id: file:human/TSG101/TSG101-uniprot.txt
      supporting_text: multivesicular bodies
    - &id027
      reference_id: PMID:12900395
      supporting_text: indirectly regulates multivesicular body formation
    - &id028
      reference_id: PMID:12900395
      supporting_text: the initial recruitment of ESCRT-I to endosomes
- term:
    id: GO:0000813
    label: ESCRT I complex
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  qualifier: part_of
  review:
    summary: ESCRT-I complex membership is the central TSG101 cellular-component annotation.
    action: ACCEPT
    reason: TSG101 is a stoichiometric core ESCRT-I subunit with VPS28, VPS37-family subunits, and
      MVB12/UBAP-family subunits.
    additional_reference_ids: *id001
    supported_by: *id002
- term:
    id: GO:0005634
    label: nucleus
  evidence_type: IEA
  original_reference_id: GO_REF:0000044
  qualifier: located_in
  review:
    summary: nucleus localization is supported but is not the core proteostasis annotation.
    action: KEEP_AS_NON_CORE
    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.
    additional_reference_ids: &id003
    - file:human/TSG101/TSG101-uniprot.txt
    - file:human/TSG101/TSG101-notes.md
    supported_by:
    - reference_id: file:human/TSG101/TSG101-uniprot.txt
      supporting_text: Mainly cytoplasmic
    - reference_id: file:human/TSG101/TSG101-uniprot.txt
      supporting_text: Nuclear localization is cell cycle-dependent
    - reference_id: file:human/TSG101/TSG101-uniprot.txt
      supporting_text: localization to the midbody during cytokinesis
- term:
    id: GO:0005737
    label: cytoplasm
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  qualifier: located_in
  review:
    summary: cytoplasm localization is supported but is not the core proteostasis annotation.
    action: KEEP_AS_NON_CORE
    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.
    additional_reference_ids: *id003
    supported_by:
    - reference_id: file:human/TSG101/TSG101-uniprot.txt
      supporting_text: Mainly cytoplasmic
    - reference_id: file:human/TSG101/TSG101-uniprot.txt
      supporting_text: Nuclear localization is cell cycle-dependent
    - reference_id: file:human/TSG101/TSG101-uniprot.txt
      supporting_text: localization to the midbody during cytokinesis
- term:
    id: GO:0005813
    label: centrosome
  evidence_type: IEA
  original_reference_id: GO_REF:0000044
  qualifier: located_in
  review:
    summary: centrosome localization is supported but is not the core proteostasis annotation.
    action: KEEP_AS_NON_CORE
    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.
    additional_reference_ids: *id003
    supported_by:
    - reference_id: file:human/TSG101/TSG101-uniprot.txt
      supporting_text: Mainly cytoplasmic
    - reference_id: file:human/TSG101/TSG101-uniprot.txt
      supporting_text: Nuclear localization is cell cycle-dependent
    - reference_id: file:human/TSG101/TSG101-uniprot.txt
      supporting_text: localization to the midbody during cytokinesis
- term:
    id: GO:0006355
    label: regulation of DNA-templated transcription
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  qualifier: involved_in
  review:
    summary: regulation of DNA-templated transcription is a legacy/non-core nuclear transcription annotation
      and likely overstates the current functional picture.
    action: MARK_AS_OVER_ANNOTATED
    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.
    additional_reference_ids: *id003
    supported_by:
    - reference_id: file:human/TSG101/TSG101-uniprot.txt
      supporting_text: May be involved in cell growth and differentiation
    - reference_id: file:human/TSG101/TSG101-uniprot.txt
      supporting_text: Acts as a negative growth regulator
- term:
    id: GO:0015031
    label: protein transport
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  qualifier: involved_in
  review:
    summary: Generic protein transport is true but should be replaced by MVB/endosome-to-lysosome cargo
      sorting terms.
    action: MODIFY
    reason: The specific TSG101 transport role is ESCRT-I sorting of ubiquitinated cargo through
      MVB/endolysosomal pathways, not undifferentiated protein transport.
    additional_reference_ids: *id001
    supported_by: *id004
    proposed_replacement_terms:
    - id: GO:0043162
      label: ubiquitin-dependent protein catabolic process via the multivesicular body sorting pathway
    - id: GO:0036258
      label: multivesicular body assembly
- term:
    id: GO:0016236
    label: macroautophagy
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  qualifier: involved_in
  review:
    summary: macroautophagy is too broad or late-fusion-biased for the TSG101 autophagy role.
    action: MODIFY
    reason: The best-supported PN autophagy interpretation is ESCRT-I-mediated phagophore/autophagosome
      closure, which is better represented by autophagosome assembly.
    additional_reference_ids: &id018
    - PMID:31519728
    - PMID:31010855
    - file:human/TSG101/TSG101-uniprot.txt
    - file:human/TSG101/TSG101-notes.md
    supported_by: &id019
    - &id029
      reference_id: PMID:31519728
      supporting_text: VPS37A directs ESCRT recruitment for phagophore closure
    - &id030
      reference_id: PMID:31519728
      supporting_text: the core ESCRT-I components TSG101 and VPS28
    - &id031
      reference_id: PMID:31519728
      supporting_text: required for autophagosome completion
    - &id032
      reference_id: PMID:31519728
      supporting_text: phagophore closure in mammalian cells
    - &id033
      reference_id: PMID:31010855
      supporting_text: mediates AP sealing
    - &id034
      reference_id: PMID:31010855
      supporting_text: ESCRT catalyzes AP closure
    proposed_replacement_terms: &id020
    - id: GO:0000045
      label: autophagosome assembly
- term:
    id: GO:0031901
    label: early endosome membrane
  evidence_type: IEA
  original_reference_id: GO_REF:0000044
  qualifier: located_in
  review:
    summary: early endosome membrane localization is supported and relevant to ESCRT-I cargo sorting.
    action: ACCEPT
    reason: TSG101 cycles between cytosol and active endosomal membranes, including early/late endosome and
      MVB contexts where ESCRT-I functions.
    additional_reference_ids:
    - PMID:12900395
    - file:human/TSG101/TSG101-uniprot.txt
    - file:human/TSG101/TSG101-notes.md
    supported_by: &id005
    - reference_id: file:human/TSG101/TSG101-uniprot.txt
      supporting_text: Early endosome membrane
    - reference_id: file:human/TSG101/TSG101-uniprot.txt
      supporting_text: Late endosome membrane
    - reference_id: PMID:12900395
      supporting_text: Tsg101 to late endosomes
    - reference_id: PMID:12900395
      supporting_text: colocalize on a subpopulation of endosomes
- term:
    id: GO:0031902
    label: late endosome membrane
  evidence_type: IEA
  original_reference_id: GO_REF:0000044
  qualifier: located_in
  review:
    summary: late endosome membrane localization is supported and relevant to ESCRT-I cargo sorting.
    action: ACCEPT
    reason: TSG101 cycles between cytosol and active endosomal membranes, including early/late endosome and
      MVB contexts where ESCRT-I functions.
    additional_reference_ids:
    - PMID:12900395
    - file:human/TSG101/TSG101-uniprot.txt
    - file:human/TSG101/TSG101-notes.md
    supported_by: *id005
- term:
    id: GO:0036258
    label: multivesicular body assembly
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  qualifier: involved_in
  review:
    summary: multivesicular body assembly is supported as part of the core ESCRT-I endosomal cargo-sorting
      role.
    action: ACCEPT
    reason: TSG101/ESCRT-I sorts ubiquitinated endocytic cargo into MVBs and thereby supports
      endosome-to-lysosome/vacuolar delivery of cargo.
    additional_reference_ids:
    - PMID:11595185
    - PMID:12900395
    - file:human/TSG101/TSG101-uniprot.txt
    - file:human/TSG101/TSG101-notes.md
    supported_by: *id004
- term:
    id: GO:0039702
    label: viral budding via host ESCRT complex
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  qualifier: involved_in
  review:
    summary: viral budding via host ESCRT complex is supported but reflects host-pathogen exploitation of
      ESCRT-I.
    action: KEEP_AS_NON_CORE
    reason: Viral budding/release annotations are well supported for TSG101 but are non-core for the human
      proteostasis-network review.
    additional_reference_ids: &id015
    - PMID:11595185
    - file:human/TSG101/TSG101-uniprot.txt
    - file:human/TSG101/TSG101-notes.md
    supported_by: &id016
    - reference_id: file:human/TSG101/TSG101-uniprot.txt
      supporting_text: Involved in the budding of many viruses
    - reference_id: file:human/TSG101/TSG101-uniprot.txt
      supporting_text: interaction is essential for viral particle budding
    - reference_id: PMID:11595185
      supporting_text: required for HIV-1 budding
    - reference_id: PMID:11595185
      supporting_text: arrests HIV-1 budding at a late stage
- term:
    id: GO:0045892
    label: negative regulation of DNA-templated transcription
  evidence_type: IEA
  original_reference_id: GO_REF:0000108
  qualifier: involved_in
  review:
    summary: negative regulation of DNA-templated transcription is a legacy/non-core nuclear transcription
      annotation and likely overstates the current functional picture.
    action: MARK_AS_OVER_ANNOTATED
    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.
    additional_reference_ids: *id003
    supported_by:
    - reference_id: file:human/TSG101/TSG101-uniprot.txt
      supporting_text: May be involved in cell growth and differentiation
    - reference_id: file:human/TSG101/TSG101-uniprot.txt
      supporting_text: Acts as a negative growth regulator
- term:
    id: GO:0090543
    label: Flemming body
  evidence_type: IEA
  original_reference_id: GO_REF:0000044
  qualifier: located_in
  review:
    summary: Flemming body localization is supported but is not the core proteostasis annotation.
    action: KEEP_AS_NON_CORE
    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.
    additional_reference_ids: *id003
    supported_by:
    - reference_id: file:human/TSG101/TSG101-uniprot.txt
      supporting_text: Mainly cytoplasmic
    - reference_id: file:human/TSG101/TSG101-uniprot.txt
      supporting_text: Nuclear localization is cell cycle-dependent
    - reference_id: file:human/TSG101/TSG101-uniprot.txt
      supporting_text: localization to the midbody during cytokinesis
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:12802020
  qualifier: enables
  review:
    summary: protein binding is too generic to represent TSG101 function.
    action: MARK_AS_OVER_ANNOTATED
    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.
    additional_reference_ids: *id001
    supported_by:
    - *id006
    - *id007
    - *id008
    - *id009
    - *id010
    - *id011
    - &id012
      reference_id: file:human/TSG101/TSG101-uniprot.txt
      supporting_text: Binds to ubiquitinated cargo proteins
    - &id013
      reference_id: file:human/TSG101/TSG101-uniprot.txt
      supporting_text: Interacts with ubiquitin
    proposed_replacement_terms: &id014
    - id: GO:0043130
      label: ubiquitin binding
    - id: GO:0000813
      label: ESCRT I complex
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:12900395
  qualifier: enables
  review:
    summary: protein binding is too generic to represent TSG101 function.
    action: MARK_AS_OVER_ANNOTATED
    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.
    additional_reference_ids: *id001
    supported_by:
    - *id006
    - *id007
    - *id008
    - *id009
    - *id010
    - *id011
    - *id012
    - *id013
    proposed_replacement_terms: *id014
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:15033475
  qualifier: enables
  review:
    summary: protein binding is too generic to represent TSG101 function.
    action: MARK_AS_OVER_ANNOTATED
    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.
    additional_reference_ids: *id001
    supported_by:
    - *id006
    - *id007
    - *id008
    - *id009
    - *id010
    - *id011
    - *id012
    - *id013
    proposed_replacement_terms: *id014
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:15611048
  qualifier: enables
  review:
    summary: protein binding is too generic to represent TSG101 function.
    action: MARK_AS_OVER_ANNOTATED
    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.
    additional_reference_ids: *id001
    supported_by:
    - *id006
    - *id007
    - *id008
    - *id009
    - *id010
    - *id011
    - *id012
    - *id013
    proposed_replacement_terms: *id014
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:16118794
  qualifier: enables
  review:
    summary: protein binding is too generic to represent TSG101 function.
    action: MARK_AS_OVER_ANNOTATED
    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.
    additional_reference_ids: *id001
    supported_by:
    - *id006
    - *id007
    - *id008
    - *id009
    - *id010
    - *id011
    - *id012
    - *id013
    proposed_replacement_terms: *id014
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:16189514
  qualifier: enables
  review:
    summary: protein binding is too generic to represent TSG101 function.
    action: MARK_AS_OVER_ANNOTATED
    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.
    additional_reference_ids: *id001
    supported_by:
    - *id006
    - *id007
    - *id008
    - *id009
    - *id010
    - *id011
    - *id012
    - *id013
    proposed_replacement_terms: *id014
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:17174262
  qualifier: enables
  review:
    summary: protein binding is too generic to represent TSG101 function.
    action: MARK_AS_OVER_ANNOTATED
    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.
    additional_reference_ids: *id001
    supported_by:
    - *id006
    - *id007
    - *id008
    - *id009
    - *id010
    - *id011
    - *id012
    - *id013
    proposed_replacement_terms: *id014
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:17350572
  qualifier: enables
  review:
    summary: protein binding is too generic to represent TSG101 function.
    action: MARK_AS_OVER_ANNOTATED
    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.
    additional_reference_ids: *id001
    supported_by:
    - *id006
    - *id007
    - *id008
    - *id009
    - *id010
    - *id011
    - *id012
    - *id013
    proposed_replacement_terms: *id014
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:17853893
  qualifier: enables
  review:
    summary: protein binding is too generic to represent TSG101 function.
    action: MARK_AS_OVER_ANNOTATED
    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.
    additional_reference_ids: *id001
    supported_by:
    - *id006
    - *id007
    - *id008
    - *id009
    - *id010
    - *id011
    - *id012
    - *id013
    proposed_replacement_terms: *id014
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:19060904
  qualifier: enables
  review:
    summary: protein binding is too generic to represent TSG101 function.
    action: MARK_AS_OVER_ANNOTATED
    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.
    additional_reference_ids: *id001
    supported_by:
    - *id006
    - *id007
    - *id008
    - *id009
    - *id010
    - *id011
    - *id012
    - *id013
    proposed_replacement_terms: *id014
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:19549727
  qualifier: enables
  review:
    summary: protein binding is too generic to represent TSG101 function.
    action: MARK_AS_OVER_ANNOTATED
    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.
    additional_reference_ids: *id001
    supported_by:
    - *id006
    - *id007
    - *id008
    - *id009
    - *id010
    - *id011
    - *id012
    - *id013
    proposed_replacement_terms: *id014
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:20176808
  qualifier: enables
  review:
    summary: protein binding is too generic to represent TSG101 function.
    action: MARK_AS_OVER_ANNOTATED
    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.
    additional_reference_ids: *id001
    supported_by:
    - *id006
    - *id007
    - *id008
    - *id009
    - *id010
    - *id011
    - *id012
    - *id013
    proposed_replacement_terms: *id014
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:25416956
  qualifier: enables
  review:
    summary: protein binding is too generic to represent TSG101 function.
    action: MARK_AS_OVER_ANNOTATED
    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.
    additional_reference_ids: *id001
    supported_by:
    - *id006
    - *id007
    - *id008
    - *id009
    - *id010
    - *id011
    - *id012
    - *id013
    proposed_replacement_terms: *id014
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:26871637
  qualifier: enables
  review:
    summary: protein binding is too generic to represent TSG101 function.
    action: MARK_AS_OVER_ANNOTATED
    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.
    additional_reference_ids: *id001
    supported_by:
    - *id006
    - *id007
    - *id008
    - *id009
    - *id010
    - *id011
    - *id012
    - *id013
    proposed_replacement_terms: *id014
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:27107012
  qualifier: enables
  review:
    summary: protein binding is too generic to represent TSG101 function.
    action: MARK_AS_OVER_ANNOTATED
    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.
    additional_reference_ids: *id001
    supported_by:
    - *id006
    - *id007
    - *id008
    - *id009
    - *id010
    - *id011
    - *id012
    - *id013
    proposed_replacement_terms: *id014
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:28514442
  qualifier: enables
  review:
    summary: protein binding is too generic to represent TSG101 function.
    action: MARK_AS_OVER_ANNOTATED
    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.
    additional_reference_ids: *id001
    supported_by:
    - *id006
    - *id007
    - *id008
    - *id009
    - *id010
    - *id011
    - *id012
    - *id013
    proposed_replacement_terms: *id014
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:31515488
  qualifier: enables
  review:
    summary: protein binding is too generic to represent TSG101 function.
    action: MARK_AS_OVER_ANNOTATED
    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.
    additional_reference_ids: *id001
    supported_by:
    - *id006
    - *id007
    - *id008
    - *id009
    - *id010
    - *id011
    - *id012
    - *id013
    proposed_replacement_terms: *id014
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:32296183
  qualifier: enables
  review:
    summary: protein binding is too generic to represent TSG101 function.
    action: MARK_AS_OVER_ANNOTATED
    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.
    additional_reference_ids: *id001
    supported_by:
    - *id006
    - *id007
    - *id008
    - *id009
    - *id010
    - *id011
    - *id012
    - *id013
    proposed_replacement_terms: *id014
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:33961781
  qualifier: enables
  review:
    summary: protein binding is too generic to represent TSG101 function.
    action: MARK_AS_OVER_ANNOTATED
    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.
    additional_reference_ids: *id001
    supported_by:
    - *id006
    - *id007
    - *id008
    - *id009
    - *id010
    - *id011
    - *id012
    - *id013
    proposed_replacement_terms: *id014
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:35044719
  qualifier: enables
  review:
    summary: protein binding is too generic to represent TSG101 function.
    action: MARK_AS_OVER_ANNOTATED
    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.
    additional_reference_ids: *id001
    supported_by:
    - *id006
    - *id007
    - *id008
    - *id009
    - *id010
    - *id011
    - *id012
    - *id013
    proposed_replacement_terms: *id014
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:35271311
  qualifier: enables
  review:
    summary: protein binding is too generic to represent TSG101 function.
    action: MARK_AS_OVER_ANNOTATED
    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.
    additional_reference_ids: *id001
    supported_by:
    - *id006
    - *id007
    - *id008
    - *id009
    - *id010
    - *id011
    - *id012
    - *id013
    proposed_replacement_terms: *id014
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:37100772
  qualifier: enables
  review:
    summary: protein binding is too generic to represent TSG101 function.
    action: MARK_AS_OVER_ANNOTATED
    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.
    additional_reference_ids: *id001
    supported_by:
    - *id006
    - *id007
    - *id008
    - *id009
    - *id010
    - *id011
    - *id012
    - *id013
    proposed_replacement_terms: *id014
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:37219487
  qualifier: enables
  review:
    summary: protein binding is too generic to represent TSG101 function.
    action: MARK_AS_OVER_ANNOTATED
    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.
    additional_reference_ids: *id001
    supported_by:
    - *id006
    - *id007
    - *id008
    - *id009
    - *id010
    - *id011
    - *id012
    - *id013
    proposed_replacement_terms: *id014
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:39526800
  qualifier: enables
  review:
    summary: protein binding is too generic to represent TSG101 function.
    action: MARK_AS_OVER_ANNOTATED
    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.
    additional_reference_ids: *id001
    supported_by:
    - *id006
    - *id007
    - *id008
    - *id009
    - *id010
    - *id011
    - *id012
    - *id013
    proposed_replacement_terms: *id014
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:40205054
  qualifier: enables
  review:
    summary: protein binding is too generic to represent TSG101 function.
    action: MARK_AS_OVER_ANNOTATED
    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.
    additional_reference_ids: *id001
    supported_by:
    - *id006
    - *id007
    - *id008
    - *id009
    - *id010
    - *id011
    - *id012
    - *id013
    proposed_replacement_terms: *id014
- term:
    id: GO:0003714
    label: transcription corepressor activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: enables
  review:
    summary: transcription corepressor activity is a legacy/non-core nuclear transcription annotation and
      likely overstates the current functional picture.
    action: MARK_AS_OVER_ANNOTATED
    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.
    additional_reference_ids: *id003
    supported_by:
    - reference_id: file:human/TSG101/TSG101-uniprot.txt
      supporting_text: May be involved in cell growth and differentiation
    - reference_id: file:human/TSG101/TSG101-uniprot.txt
      supporting_text: Acts as a negative growth regulator
- term:
    id: GO:0046755
    label: viral budding
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: involved_in
  review:
    summary: viral budding is supported but reflects host-pathogen exploitation of ESCRT-I.
    action: KEEP_AS_NON_CORE
    reason: Viral budding/release annotations are well supported for TSG101 but are non-core for the human
      proteostasis-network review.
    additional_reference_ids: *id015
    supported_by: *id016
- term:
    id: GO:0070062
    label: extracellular exosome
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: located_in
  review:
    summary: Extracellular exosome detection is supported but is a non-core localization/context.
    action: KEEP_AS_NON_CORE
    reason: TSG101 is commonly detected in exosome preparations and regulates exosomal release, but this is
      secondary to its ESCRT-I membrane-remodeling role.
    additional_reference_ids: *id003
    supported_by: &id017
    - reference_id: file:human/TSG101/TSG101-uniprot.txt
      supporting_text: Required for the exosomal release of SDCBP, CD63 and syndecan
    - reference_id: file:human/TSG101/TSG101-uniprot.txt
      supporting_text: extracellular release of microvesicles
- term:
    id: GO:1990182
    label: exosomal secretion
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: involved_in
  review:
    summary: exosomal secretion is supported but non-core in this PN review.
    action: KEEP_AS_NON_CORE
    reason: TSG101 contributes to exosome/microvesicle release, but the proteostasis core here is ESCRT-I
      endosomal cargo sorting and autophagophore closure.
    additional_reference_ids: *id003
    supported_by: *id017
- term:
    id: GO:2000397
    label: positive regulation of ubiquitin-dependent endocytosis
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: involved_in
  review:
    summary: positive regulation of ubiquitin-dependent endocytosis is supported as a cargo-sorting
      consequence of ESCRT-I function.
    action: ACCEPT
    reason: TSG101-mediated ESCRT-I sorting of ubiquitinated receptors into the MVB/lysosomal pathway explains
      EGFR/endocytosis down-regulation annotations.
    additional_reference_ids:
    - PMID:12900395
    - file:human/TSG101/TSG101-uniprot.txt
    - file:human/TSG101/TSG101-notes.md
    supported_by: *id004
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: IDA
  original_reference_id: GO_REF:0000052
  qualifier: located_in
  review:
    summary: cytosol localization is supported but is not the core proteostasis annotation.
    action: KEEP_AS_NON_CORE
    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.
    additional_reference_ids: *id003
    supported_by:
    - reference_id: file:human/TSG101/TSG101-uniprot.txt
      supporting_text: Mainly cytoplasmic
    - reference_id: file:human/TSG101/TSG101-uniprot.txt
      supporting_text: Nuclear localization is cell cycle-dependent
    - reference_id: file:human/TSG101/TSG101-uniprot.txt
      supporting_text: localization to the midbody during cytokinesis
- term:
    id: GO:0005634
    label: nucleus
  evidence_type: EXP
  original_reference_id: PMID:17229889
  qualifier: located_in
  review:
    summary: nucleus localization is supported but is not the core proteostasis annotation.
    action: KEEP_AS_NON_CORE
    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.
    additional_reference_ids: *id003
    supported_by:
    - reference_id: file:human/TSG101/TSG101-uniprot.txt
      supporting_text: Mainly cytoplasmic
    - reference_id: file:human/TSG101/TSG101-uniprot.txt
      supporting_text: Nuclear localization is cell cycle-dependent
    - reference_id: file:human/TSG101/TSG101-uniprot.txt
      supporting_text: localization to the midbody during cytokinesis
- term:
    id: GO:0005737
    label: cytoplasm
  evidence_type: EXP
  original_reference_id: PMID:17853893
  qualifier: located_in
  review:
    summary: cytoplasm localization is supported but is not the core proteostasis annotation.
    action: KEEP_AS_NON_CORE
    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.
    additional_reference_ids: *id003
    supported_by:
    - reference_id: file:human/TSG101/TSG101-uniprot.txt
      supporting_text: Mainly cytoplasmic
    - reference_id: file:human/TSG101/TSG101-uniprot.txt
      supporting_text: Nuclear localization is cell cycle-dependent
    - reference_id: file:human/TSG101/TSG101-uniprot.txt
      supporting_text: localization to the midbody during cytokinesis
- term:
    id: GO:0031901
    label: early endosome membrane
  evidence_type: EXP
  original_reference_id: PMID:23166352
  qualifier: located_in
  review:
    summary: early endosome membrane localization is supported and relevant to ESCRT-I cargo sorting.
    action: ACCEPT
    reason: TSG101 cycles between cytosol and active endosomal membranes, including early/late endosome and
      MVB contexts where ESCRT-I functions.
    additional_reference_ids:
    - PMID:12900395
    - file:human/TSG101/TSG101-uniprot.txt
    - file:human/TSG101/TSG101-notes.md
    supported_by: *id005
- term:
    id: GO:0031902
    label: late endosome membrane
  evidence_type: EXP
  original_reference_id: PMID:11916981
  qualifier: located_in
  review:
    summary: late endosome membrane localization is supported and relevant to ESCRT-I cargo sorting.
    action: ACCEPT
    reason: TSG101 cycles between cytosol and active endosomal membranes, including early/late endosome and
      MVB contexts where ESCRT-I functions.
    additional_reference_ids:
    - PMID:12900395
    - file:human/TSG101/TSG101-uniprot.txt
    - file:human/TSG101/TSG101-notes.md
    supported_by: *id005
- term:
    id: GO:0031902
    label: late endosome membrane
  evidence_type: EXP
  original_reference_id: PMID:17229889
  qualifier: located_in
  review:
    summary: late endosome membrane localization is supported and relevant to ESCRT-I cargo sorting.
    action: ACCEPT
    reason: TSG101 cycles between cytosol and active endosomal membranes, including early/late endosome and
      MVB contexts where ESCRT-I functions.
    additional_reference_ids:
    - PMID:12900395
    - file:human/TSG101/TSG101-uniprot.txt
    - file:human/TSG101/TSG101-notes.md
    supported_by: *id005
- term:
    id: GO:0061631
    label: ubiquitin conjugating enzyme activity
  evidence_type: IKR
  original_reference_id: PMID:9241264
  qualifier: enables
  negated: true
  review:
    summary: The negated ubiquitin-conjugating-enzyme annotation is correct for TSG101.
    action: ACCEPT
    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.
    additional_reference_ids:
    - PMID:9241264
    - file:human/TSG101/TSG101-uniprot.txt
    - file:human/TSG101/TSG101-notes.md
    supported_by:
    - reference_id: file:human/TSG101/TSG101-uniprot.txt
      supporting_text: The UEV domain binds ubiquitin
    - reference_id: file:human/TSG101/TSG101-uniprot.txt
      supporting_text: P-[ST]-A-P peptide motif independently
    - reference_id: file:human/TSG101/TSG101-uniprot.txt
      supporting_text: Belongs to the ubiquitin-conjugating enzyme family. UEV
- term:
    id: GO:0000813
    label: ESCRT I complex
  evidence_type: IPI
  original_reference_id: PMID:18005716
  qualifier: part_of
  review:
    summary: ESCRT-I complex membership is the central TSG101 cellular-component annotation.
    action: ACCEPT
    reason: TSG101 is a stoichiometric core ESCRT-I subunit with VPS28, VPS37-family subunits, and
      MVB12/UBAP-family subunits.
    additional_reference_ids: *id001
    supported_by: *id002
- term:
    id: GO:0000813
    label: ESCRT I complex
  evidence_type: IPI
  original_reference_id: PMID:21757351
  qualifier: part_of
  review:
    summary: ESCRT-I complex membership is the central TSG101 cellular-component annotation.
    action: ACCEPT
    reason: TSG101 is a stoichiometric core ESCRT-I subunit with VPS28, VPS37-family subunits, and
      MVB12/UBAP-family subunits.
    additional_reference_ids: *id001
    supported_by: *id002
- term:
    id: GO:0000813
    label: ESCRT I complex
  evidence_type: IPI
  original_reference_id: PMID:32424346
  qualifier: part_of
  review:
    summary: ESCRT-I complex membership is the central TSG101 cellular-component annotation.
    action: ACCEPT
    reason: TSG101 is a stoichiometric core ESCRT-I subunit with VPS28, VPS37-family subunits, and
      MVB12/UBAP-family subunits.
    additional_reference_ids: *id001
    supported_by: *id002
- term:
    id: GO:0010008
    label: endosome membrane
  evidence_type: NAS
  original_reference_id: PMID:32424346
  qualifier: located_in
  review:
    summary: endosome membrane localization is supported and relevant to ESCRT-I cargo sorting.
    action: ACCEPT
    reason: TSG101 cycles between cytosol and active endosomal membranes, including early/late endosome and
      MVB contexts where ESCRT-I functions.
    additional_reference_ids:
    - PMID:12900395
    - file:human/TSG101/TSG101-uniprot.txt
    - file:human/TSG101/TSG101-notes.md
    supported_by: *id005
- term:
    id: GO:0036258
    label: multivesicular body assembly
  evidence_type: NAS
  original_reference_id: PMID:32424346
  qualifier: involved_in
  review:
    summary: multivesicular body assembly is supported as part of the core ESCRT-I endosomal cargo-sorting
      role.
    action: ACCEPT
    reason: TSG101/ESCRT-I sorts ubiquitinated endocytic cargo into MVBs and thereby supports
      endosome-to-lysosome/vacuolar delivery of cargo.
    additional_reference_ids:
    - PMID:11595185
    - PMID:12900395
    - file:human/TSG101/TSG101-uniprot.txt
    - file:human/TSG101/TSG101-notes.md
    supported_by: *id004
- term:
    id: GO:0043328
    label: protein transport to vacuole involved in ubiquitin-dependent protein catabolic process via the
      multivesicular body sorting pathway
  evidence_type: NAS
  original_reference_id: PMID:32424346
  qualifier: involved_in
  review:
    summary: protein transport to vacuole involved in ubiquitin-dependent protein catabolic process via the
      multivesicular body sorting pathway is supported as part of the core ESCRT-I endosomal cargo-sorting
      role.
    action: ACCEPT
    reason: TSG101/ESCRT-I sorts ubiquitinated endocytic cargo into MVBs and thereby supports
      endosome-to-lysosome/vacuolar delivery of cargo.
    additional_reference_ids:
    - PMID:11595185
    - PMID:12900395
    - file:human/TSG101/TSG101-uniprot.txt
    - file:human/TSG101/TSG101-notes.md
    supported_by: *id004
- term:
    id: GO:0090148
    label: membrane fission
  evidence_type: NAS
  original_reference_id: PMID:32424346
  qualifier: involved_in
  review:
    summary: Membrane fission is supported as the shared ESCRT reverse-topology membrane-remodeling activity.
    action: ACCEPT
    reason: ESCRT-I participates upstream of ESCRT-III/VPS4-driven neck scission in MVB formation,
      cytokinesis/viral budding, and phagophore closure contexts.
    additional_reference_ids:
    - PMID:20588296
    - PMID:31519728
    - file:human/TSG101/TSG101-uniprot.txt
    - file:human/TSG101/TSG101-notes.md
    supported_by:
    - reference_id: PMID:20588296
      supporting_text: ESCRT-I and ESCRT-II direct membrane budding away from the cytosol
    - reference_id: PMID:31519728
      supporting_text: ESCRT-mediated membrane scission in phagophore closure
    - reference_id: PMID:31519728
      supporting_text: the core ESCRT-I components TSG101 and VPS28
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:15218037
  qualifier: enables
  review:
    summary: protein binding is too generic to represent TSG101 function.
    action: MARK_AS_OVER_ANNOTATED
    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.
    additional_reference_ids: *id001
    supported_by:
    - *id006
    - *id007
    - *id008
    - *id009
    - *id010
    - *id011
    - *id012
    - *id013
    proposed_replacement_terms: *id014
- term:
    id: GO:1903774
    label: positive regulation of viral budding via host ESCRT complex
  evidence_type: IMP
  original_reference_id: PMID:11595185
  qualifier: involved_in
  review:
    summary: positive regulation of viral budding via host ESCRT complex is supported but reflects
      host-pathogen exploitation of ESCRT-I.
    action: KEEP_AS_NON_CORE
    reason: Viral budding/release annotations are well supported for TSG101 but are non-core for the human
      proteostasis-network review.
    additional_reference_ids: *id015
    supported_by: *id016
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:18005716
  qualifier: enables
  review:
    summary: protein binding is too generic to represent TSG101 function.
    action: MARK_AS_OVER_ANNOTATED
    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.
    additional_reference_ids: *id001
    supported_by:
    - *id006
    - *id007
    - *id008
    - *id009
    - *id010
    - *id011
    - *id012
    - *id013
    proposed_replacement_terms: *id014
- term:
    id: GO:0046755
    label: viral budding
  evidence_type: IMP
  original_reference_id: PMID:18005716
  qualifier: involved_in
  review:
    summary: viral budding is supported but reflects host-pathogen exploitation of ESCRT-I.
    action: KEEP_AS_NON_CORE
    reason: Viral budding/release annotations are well supported for TSG101 but are non-core for the human
      proteostasis-network review.
    additional_reference_ids: *id015
    supported_by: *id016
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:22315426
  qualifier: enables
  review:
    summary: protein binding is too generic to represent TSG101 function.
    action: MARK_AS_OVER_ANNOTATED
    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.
    additional_reference_ids: *id001
    supported_by:
    - *id006
    - *id007
    - *id008
    - *id009
    - *id010
    - *id011
    - *id012
    - *id013
    proposed_replacement_terms: *id014
- term:
    id: GO:0006858
    label: extracellular transport
  evidence_type: IMP
  original_reference_id: PMID:22315426
  qualifier: involved_in
  review:
    summary: extracellular transport is supported but non-core in this PN review.
    action: KEEP_AS_NON_CORE
    reason: TSG101 contributes to exosome/microvesicle release, but the proteostasis core here is ESCRT-I
      endosomal cargo sorting and autophagophore closure.
    additional_reference_ids: *id003
    supported_by: *id017
- term:
    id: GO:0007175
    label: negative regulation of epidermal growth factor-activated receptor activity
  evidence_type: IMP
  original_reference_id: PMID:16973552
  qualifier: involved_in
  review:
    summary: negative regulation of epidermal growth factor-activated receptor activity is supported as a
      cargo-sorting consequence of ESCRT-I function.
    action: ACCEPT
    reason: TSG101-mediated ESCRT-I sorting of ubiquitinated receptors into the MVB/lysosomal pathway explains
      EGFR/endocytosis down-regulation annotations.
    additional_reference_ids:
    - PMID:12900395
    - file:human/TSG101/TSG101-uniprot.txt
    - file:human/TSG101/TSG101-notes.md
    supported_by: *id004
- term:
    id: GO:0044877
    label: protein-containing complex binding
  evidence_type: IDA
  original_reference_id: PMID:16973552
  qualifier: enables
  review:
    summary: protein-containing complex binding is too generic to represent TSG101 function.
    action: MARK_AS_OVER_ANNOTATED
    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.
    additional_reference_ids: *id001
    supported_by:
    - *id006
    - *id007
    - *id008
    - *id009
    - *id010
    - *id011
    - *id012
    - *id013
    proposed_replacement_terms: *id014
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:18641129
  qualifier: enables
  review:
    summary: protein binding is too generic to represent TSG101 function.
    action: MARK_AS_OVER_ANNOTATED
    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.
    additional_reference_ids: *id001
    supported_by:
    - *id006
    - *id007
    - *id008
    - *id009
    - *id010
    - *id011
    - *id012
    - *id013
    proposed_replacement_terms: *id014
- term:
    id: GO:0016236
    label: macroautophagy
  evidence_type: TAS
  original_reference_id: PMID:20588296
  qualifier: involved_in
  review:
    summary: macroautophagy is too broad or late-fusion-biased for the TSG101 autophagy role.
    action: MODIFY
    reason: The best-supported PN autophagy interpretation is ESCRT-I-mediated phagophore/autophagosome
      closure, which is better represented by autophagosome assembly.
    additional_reference_ids: *id018
    supported_by: *id019
    proposed_replacement_terms: *id020
- term:
    id: GO:0042059
    label: negative regulation of epidermal growth factor receptor signaling pathway
  evidence_type: IMP
  original_reference_id: PMID:16554368
  qualifier: involved_in
  review:
    summary: negative regulation of epidermal growth factor receptor signaling pathway is supported as a
      cargo-sorting consequence of ESCRT-I function.
    action: ACCEPT
    reason: TSG101-mediated ESCRT-I sorting of ubiquitinated receptors into the MVB/lysosomal pathway explains
      EGFR/endocytosis down-regulation annotations.
    additional_reference_ids:
    - PMID:12900395
    - file:human/TSG101/TSG101-uniprot.txt
    - file:human/TSG101/TSG101-notes.md
    supported_by: *id004
- term:
    id: GO:0000813
    label: ESCRT I complex
  evidence_type: TAS
  original_reference_id: PMID:20588296
  qualifier: part_of
  review:
    summary: ESCRT-I complex membership is the central TSG101 cellular-component annotation.
    action: ACCEPT
    reason: TSG101 is a stoichiometric core ESCRT-I subunit with VPS28, VPS37-family subunits, and
      MVB12/UBAP-family subunits.
    additional_reference_ids: *id001
    supported_by: *id002
- term:
    id: GO:0036258
    label: multivesicular body assembly
  evidence_type: TAS
  original_reference_id: PMID:20588296
  qualifier: involved_in
  review:
    summary: multivesicular body assembly is supported as part of the core ESCRT-I endosomal cargo-sorting
      role.
    action: ACCEPT
    reason: TSG101/ESCRT-I sorts ubiquitinated endocytic cargo into MVBs and thereby supports
      endosome-to-lysosome/vacuolar delivery of cargo.
    additional_reference_ids:
    - PMID:11595185
    - PMID:12900395
    - file:human/TSG101/TSG101-uniprot.txt
    - file:human/TSG101/TSG101-notes.md
    supported_by: *id004
- term:
    id: GO:0039702
    label: viral budding via host ESCRT complex
  evidence_type: TAS
  original_reference_id: PMID:20588296
  qualifier: involved_in
  review:
    summary: viral budding via host ESCRT complex is supported but reflects host-pathogen exploitation of
      ESCRT-I.
    action: KEEP_AS_NON_CORE
    reason: Viral budding/release annotations are well supported for TSG101 but are non-core for the human
      proteostasis-network review.
    additional_reference_ids: *id015
    supported_by: *id016
- term:
    id: GO:0000813
    label: ESCRT I complex
  evidence_type: TAS
  original_reference_id: PMID:21118109
  qualifier: part_of
  review:
    summary: ESCRT-I complex membership is the central TSG101 cellular-component annotation.
    action: ACCEPT
    reason: TSG101 is a stoichiometric core ESCRT-I subunit with VPS28, VPS37-family subunits, and
      MVB12/UBAP-family subunits.
    additional_reference_ids: *id001
    supported_by: *id002
- term:
    id: GO:0097352
    label: autophagosome maturation
  evidence_type: TAS
  original_reference_id: PMID:21118109
  qualifier: involved_in
  review:
    summary: autophagosome maturation is too broad or late-fusion-biased for the TSG101 autophagy role.
    action: MODIFY
    reason: The best-supported PN autophagy interpretation is ESCRT-I-mediated phagophore/autophagosome
      closure, which is better represented by autophagosome assembly.
    additional_reference_ids: *id018
    supported_by: *id019
    proposed_replacement_terms: *id020
- term:
    id: GO:0043405
    label: regulation of MAP kinase activity
  evidence_type: IMP
  original_reference_id: PMID:17714434
  qualifier: involved_in
  review:
    summary: MAP kinase regulation is a downstream receptor-signaling consequence and not core.
    action: KEEP_AS_NON_CORE
    reason: This likely reflects altered EGFR trafficking/signaling downstream of ESCRT function rather than a
      direct TSG101 molecular role.
    additional_reference_ids:
    - PMID:12900395
    - file:human/TSG101/TSG101-uniprot.txt
    - file:human/TSG101/TSG101-notes.md
    supported_by: *id004
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:16973552
  qualifier: enables
  review:
    summary: protein binding is too generic to represent TSG101 function.
    action: MARK_AS_OVER_ANNOTATED
    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.
    additional_reference_ids: *id001
    supported_by:
    - *id006
    - *id007
    - *id008
    - *id009
    - *id010
    - *id011
    - *id012
    - *id013
    proposed_replacement_terms: *id014
- term:
    id: GO:0019076
    label: viral release from host cell
  evidence_type: IMP
  original_reference_id: PMID:11595185
  qualifier: involved_in
  review:
    summary: viral release from host cell is supported but reflects host-pathogen exploitation of ESCRT-I.
    action: KEEP_AS_NON_CORE
    reason: Viral budding/release annotations are well supported for TSG101 but are non-core for the human
      proteostasis-network review.
    additional_reference_ids: *id015
    supported_by: *id016
- term:
    id: GO:0043130
    label: ubiquitin binding
  evidence_type: IDA
  original_reference_id: PMID:11595185
  qualifier: enables
  review:
    summary: Ubiquitin binding is a core TSG101 UEV-domain molecular function.
    action: ACCEPT
    reason: TSG101 binds ubiquitin/ubiquitinated cargo through its UEV domain and uses that activity in
      ESCRT-I cargo sorting and PTAP-motif recruitment contexts.
    additional_reference_ids:
    - PMID:11595185
    - file:human/TSG101/TSG101-uniprot.txt
    - file:human/TSG101/TSG101-notes.md
    supported_by: &id021
    - *id012
    - *id013
    - &id022
      reference_id: file:human/TSG101/TSG101-uniprot.txt
      supporting_text: The UEV domain binds ubiquitin
    - &id023
      reference_id: PMID:11595185
      supporting_text: UEV domain of Tsg101 binds
    - &id024
      reference_id: PMID:11595185
      supporting_text: to ubiquitin
- term:
    id: GO:0046790
    label: virion binding
  evidence_type: IDA
  original_reference_id: PMID:11595185
  qualifier: enables
  review:
    summary: virion binding is supported but reflects host-pathogen exploitation of ESCRT-I.
    action: KEEP_AS_NON_CORE
    reason: Viral budding/release annotations are well supported for TSG101 but are non-core for the human
      proteostasis-network review.
    additional_reference_ids: *id015
    supported_by: *id016
- term:
    id: GO:0000813
    label: ESCRT I complex
  evidence_type: IDA
  original_reference_id: PMID:18005716
  qualifier: part_of
  review:
    summary: ESCRT-I complex membership is the central TSG101 cellular-component annotation.
    action: ACCEPT
    reason: TSG101 is a stoichiometric core ESCRT-I subunit with VPS28, VPS37-family subunits, and
      MVB12/UBAP-family subunits.
    additional_reference_ids: *id001
    supported_by: *id002
- term:
    id: GO:0005768
    label: endosome
  evidence_type: IDA
  original_reference_id: PMID:17940959
  qualifier: located_in
  review:
    summary: endosome localization is supported and relevant to ESCRT-I cargo sorting.
    action: ACCEPT
    reason: TSG101 cycles between cytosol and active endosomal membranes, including early/late endosome and
      MVB contexts where ESCRT-I functions.
    additional_reference_ids:
    - PMID:12900395
    - file:human/TSG101/TSG101-uniprot.txt
    - file:human/TSG101/TSG101-notes.md
    supported_by: *id005
- term:
    id: GO:0005886
    label: plasma membrane
  evidence_type: IDA
  original_reference_id: PMID:17940959
  qualifier: located_in
  review:
    summary: plasma membrane localization is supported but is not the core proteostasis annotation.
    action: KEEP_AS_NON_CORE
    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.
    additional_reference_ids: *id003
    supported_by:
    - reference_id: file:human/TSG101/TSG101-uniprot.txt
      supporting_text: Mainly cytoplasmic
    - reference_id: file:human/TSG101/TSG101-uniprot.txt
      supporting_text: Nuclear localization is cell cycle-dependent
    - reference_id: file:human/TSG101/TSG101-uniprot.txt
      supporting_text: localization to the midbody during cytokinesis
- term:
    id: GO:1903774
    label: positive regulation of viral budding via host ESCRT complex
  evidence_type: IMP
  original_reference_id: PMID:15218037
  qualifier: involved_in
  review:
    summary: positive regulation of viral budding via host ESCRT complex is supported but reflects
      host-pathogen exploitation of ESCRT-I.
    action: KEEP_AS_NON_CORE
    reason: Viral budding/release annotations are well supported for TSG101 but are non-core for the human
      proteostasis-network review.
    additional_reference_ids: *id015
    supported_by: *id016
- term:
    id: GO:0019076
    label: viral release from host cell
  evidence_type: IMP
  original_reference_id: PMID:15218037
  qualifier: involved_in
  review:
    summary: viral release from host cell is supported but reflects host-pathogen exploitation of ESCRT-I.
    action: KEEP_AS_NON_CORE
    reason: Viral budding/release annotations are well supported for TSG101 but are non-core for the human
      proteostasis-network review.
    additional_reference_ids: *id015
    supported_by: *id016
- term:
    id: GO:0005769
    label: early endosome
  evidence_type: IDA
  original_reference_id: PMID:11916981
  qualifier: located_in
  review:
    summary: early endosome localization is supported and relevant to ESCRT-I cargo sorting.
    action: ACCEPT
    reason: TSG101 cycles between cytosol and active endosomal membranes, including early/late endosome and
      MVB contexts where ESCRT-I functions.
    additional_reference_ids:
    - PMID:12900395
    - file:human/TSG101/TSG101-uniprot.txt
    - file:human/TSG101/TSG101-notes.md
    supported_by: *id005
- term:
    id: GO:0043130
    label: ubiquitin binding
  evidence_type: IDA
  original_reference_id: PMID:11916981
  qualifier: enables
  review:
    summary: Ubiquitin binding is a core TSG101 UEV-domain molecular function.
    action: ACCEPT
    reason: TSG101 binds ubiquitin/ubiquitinated cargo through its UEV domain and uses that activity in
      ESCRT-I cargo sorting and PTAP-motif recruitment contexts.
    additional_reference_ids:
    - PMID:11595185
    - file:human/TSG101/TSG101-uniprot.txt
    - file:human/TSG101/TSG101-notes.md
    supported_by: *id021
- term:
    id: GO:1903551
    label: regulation of extracellular exosome assembly
  evidence_type: IMP
  original_reference_id: PMID:24105262
  qualifier: involved_in
  review:
    summary: regulation of extracellular exosome assembly is supported but non-core in this PN review.
    action: KEEP_AS_NON_CORE
    reason: TSG101 contributes to exosome/microvesicle release, but the proteostasis core here is ESCRT-I
      endosomal cargo sorting and autophagophore closure.
    additional_reference_ids: *id003
    supported_by: *id017
- term:
    id: GO:1903543
    label: positive regulation of exosomal secretion
  evidence_type: IMP
  original_reference_id: PMID:22660413
  qualifier: involved_in
  review:
    summary: positive regulation of exosomal secretion is supported but non-core in this PN review.
    action: KEEP_AS_NON_CORE
    reason: TSG101 contributes to exosome/microvesicle release, but the proteostasis core here is ESCRT-I
      endosomal cargo sorting and autophagophore closure.
    additional_reference_ids: *id003
    supported_by: *id017
- term:
    id: GO:1903543
    label: positive regulation of exosomal secretion
  evidence_type: IMP
  original_reference_id: PMID:24105262
  qualifier: involved_in
  review:
    summary: positive regulation of exosomal secretion is supported but non-core in this PN review.
    action: KEEP_AS_NON_CORE
    reason: TSG101 contributes to exosome/microvesicle release, but the proteostasis core here is ESCRT-I
      endosomal cargo sorting and autophagophore closure.
    additional_reference_ids: *id003
    supported_by: *id017
- term:
    id: GO:0070062
    label: extracellular exosome
  evidence_type: IDA
  original_reference_id: PMID:23092844
  qualifier: located_in
  review:
    summary: Extracellular exosome detection is supported but is a non-core localization/context.
    action: KEEP_AS_NON_CORE
    reason: TSG101 is commonly detected in exosome preparations and regulates exosomal release, but this is
      secondary to its ESCRT-I membrane-remodeling role.
    additional_reference_ids: *id003
    supported_by: *id017
- term:
    id: GO:0070062
    label: extracellular exosome
  evidence_type: HDA
  original_reference_id: PMID:23533145
  qualifier: located_in
  review:
    summary: Extracellular exosome detection is supported but is a non-core localization/context.
    action: KEEP_AS_NON_CORE
    reason: TSG101 is commonly detected in exosome preparations and regulates exosomal release, but this is
      secondary to its ESCRT-I membrane-remodeling role.
    additional_reference_ids: *id003
    supported_by: *id017
- term:
    id: GO:0070062
    label: extracellular exosome
  evidence_type: IDA
  original_reference_id: PMID:16501490
  qualifier: located_in
  review:
    summary: Extracellular exosome detection is supported but is a non-core localization/context.
    action: KEEP_AS_NON_CORE
    reason: TSG101 is commonly detected in exosome preparations and regulates exosomal release, but this is
      secondary to its ESCRT-I membrane-remodeling role.
    additional_reference_ids: *id003
    supported_by: *id017
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:14519844
  qualifier: enables
  review:
    summary: protein binding is too generic to represent TSG101 function.
    action: MARK_AS_OVER_ANNOTATED
    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.
    additional_reference_ids: *id001
    supported_by:
    - *id006
    - *id007
    - *id008
    - *id009
    - *id010
    - *id011
    - *id012
    - *id013
    proposed_replacement_terms: *id014
- term:
    id: GO:0042803
    label: protein homodimerization activity
  evidence_type: IPI
  original_reference_id: PMID:14519844
  qualifier: enables
  review:
    summary: Homodimerization is supported as a structural interaction but is not the core functional
      annotation.
    action: KEEP_AS_NON_CORE
    reason: Retain this as a non-core interaction property; ESCRT-I complex membership and ubiquitin binding
      capture the main TSG101 role.
    additional_reference_ids: *id003
    supported_by:
    - reference_id: file:human/TSG101/TSG101-uniprot.txt
      supporting_text: Self-associates
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:14505570
  qualifier: enables
  review:
    summary: protein binding is too generic to represent TSG101 function.
    action: MARK_AS_OVER_ANNOTATED
    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.
    additional_reference_ids: *id001
    supported_by:
    - *id006
    - *id007
    - *id008
    - *id009
    - *id010
    - *id011
    - *id012
    - *id013
    proposed_replacement_terms: *id014
- term:
    id: GO:0000813
    label: ESCRT I complex
  evidence_type: IDA
  original_reference_id: PMID:20654576
  qualifier: part_of
  review:
    summary: ESCRT-I complex membership is the central TSG101 cellular-component annotation.
    action: ACCEPT
    reason: TSG101 is a stoichiometric core ESCRT-I subunit with VPS28, VPS37-family subunits, and
      MVB12/UBAP-family subunits.
    additional_reference_ids: *id001
    supported_by: *id002
- term:
    id: GO:0000813
    label: ESCRT I complex
  evidence_type: IDA
  original_reference_id: PMID:22232651
  qualifier: part_of
  review:
    summary: ESCRT-I complex membership is the central TSG101 cellular-component annotation.
    action: ACCEPT
    reason: TSG101 is a stoichiometric core ESCRT-I subunit with VPS28, VPS37-family subunits, and
      MVB12/UBAP-family subunits.
    additional_reference_ids: *id001
    supported_by: *id002
- term:
    id: GO:0043130
    label: ubiquitin binding
  evidence_type: IDA
  original_reference_id: PMID:20654576
  qualifier: enables
  review:
    summary: Ubiquitin binding is a core TSG101 UEV-domain molecular function.
    action: ACCEPT
    reason: TSG101 binds ubiquitin/ubiquitinated cargo through its UEV domain and uses that activity in
      ESCRT-I cargo sorting and PTAP-motif recruitment contexts.
    additional_reference_ids:
    - PMID:11595185
    - file:human/TSG101/TSG101-uniprot.txt
    - file:human/TSG101/TSG101-notes.md
    supported_by: *id021
- term:
    id: GO:0043162
    label: ubiquitin-dependent protein catabolic process via the multivesicular body sorting pathway
  evidence_type: IC
  original_reference_id: PMID:20654576
  qualifier: involved_in
  review:
    summary: ubiquitin-dependent protein catabolic process via the multivesicular body sorting pathway is
      supported as part of the core ESCRT-I endosomal cargo-sorting role.
    action: ACCEPT
    reason: TSG101/ESCRT-I sorts ubiquitinated endocytic cargo into MVBs and thereby supports
      endosome-to-lysosome/vacuolar delivery of cargo.
    additional_reference_ids:
    - PMID:11595185
    - PMID:12900395
    - file:human/TSG101/TSG101-uniprot.txt
    - file:human/TSG101/TSG101-notes.md
    supported_by: *id004
- term:
    id: GO:0070062
    label: extracellular exosome
  evidence_type: HDA
  original_reference_id: PMID:19056867
  qualifier: located_in
  review:
    summary: Extracellular exosome detection is supported but is a non-core localization/context.
    action: KEEP_AS_NON_CORE
    reason: TSG101 is commonly detected in exosome preparations and regulates exosomal release, but this is
      secondary to its ESCRT-I membrane-remodeling role.
    additional_reference_ids: *id003
    supported_by: *id017
- term:
    id: GO:0010008
    label: endosome membrane
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-184269
  qualifier: located_in
  review:
    summary: endosome membrane localization is supported and relevant to ESCRT-I cargo sorting.
    action: ACCEPT
    reason: TSG101 cycles between cytosol and active endosomal membranes, including early/late endosome and
      MVB contexts where ESCRT-I functions.
    additional_reference_ids:
    - PMID:12900395
    - file:human/TSG101/TSG101-uniprot.txt
    - file:human/TSG101/TSG101-notes.md
    supported_by: *id005
- term:
    id: GO:0010008
    label: endosome membrane
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-3149434
  qualifier: located_in
  review:
    summary: endosome membrane localization is supported and relevant to ESCRT-I cargo sorting.
    action: ACCEPT
    reason: TSG101 cycles between cytosol and active endosomal membranes, including early/late endosome and
      MVB contexts where ESCRT-I functions.
    additional_reference_ids:
    - PMID:12900395
    - file:human/TSG101/TSG101-uniprot.txt
    - file:human/TSG101/TSG101-notes.md
    supported_by: *id005
- term:
    id: GO:0010008
    label: endosome membrane
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-3159232
  qualifier: located_in
  review:
    summary: endosome membrane localization is supported and relevant to ESCRT-I cargo sorting.
    action: ACCEPT
    reason: TSG101 cycles between cytosol and active endosomal membranes, including early/late endosome and
      MVB contexts where ESCRT-I functions.
    additional_reference_ids:
    - PMID:12900395
    - file:human/TSG101/TSG101-uniprot.txt
    - file:human/TSG101/TSG101-notes.md
    supported_by: *id005
- term:
    id: GO:0010008
    label: endosome membrane
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-917696
  qualifier: located_in
  review:
    summary: endosome membrane localization is supported and relevant to ESCRT-I cargo sorting.
    action: ACCEPT
    reason: TSG101 cycles between cytosol and active endosomal membranes, including early/late endosome and
      MVB contexts where ESCRT-I functions.
    additional_reference_ids:
    - PMID:12900395
    - file:human/TSG101/TSG101-uniprot.txt
    - file:human/TSG101/TSG101-notes.md
    supported_by: *id005
- term:
    id: GO:0010008
    label: endosome membrane
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-917730
  qualifier: located_in
  review:
    summary: endosome membrane localization is supported and relevant to ESCRT-I cargo sorting.
    action: ACCEPT
    reason: TSG101 cycles between cytosol and active endosomal membranes, including early/late endosome and
      MVB contexts where ESCRT-I functions.
    additional_reference_ids:
    - PMID:12900395
    - file:human/TSG101/TSG101-uniprot.txt
    - file:human/TSG101/TSG101-notes.md
    supported_by: *id005
- term:
    id: GO:0070062
    label: extracellular exosome
  evidence_type: IDA
  original_reference_id: PMID:15326289
  qualifier: located_in
  review:
    summary: Extracellular exosome detection is supported but is a non-core localization/context.
    action: KEEP_AS_NON_CORE
    reason: TSG101 is commonly detected in exosome preparations and regulates exosomal release, but this is
      secondary to its ESCRT-I membrane-remodeling role.
    additional_reference_ids: *id003
    supported_by: *id017
- term:
    id: GO:0000813
    label: ESCRT I complex
  evidence_type: IDA
  original_reference_id: PMID:21757351
  qualifier: part_of
  review:
    summary: ESCRT-I complex membership is the central TSG101 cellular-component annotation.
    action: ACCEPT
    reason: TSG101 is a stoichiometric core ESCRT-I subunit with VPS28, VPS37-family subunits, and
      MVB12/UBAP-family subunits.
    additional_reference_ids: *id001
    supported_by: *id002
- term:
    id: GO:0043162
    label: ubiquitin-dependent protein catabolic process via the multivesicular body sorting pathway
  evidence_type: IMP
  original_reference_id: PMID:21757351
  qualifier: involved_in
  review:
    summary: ubiquitin-dependent protein catabolic process via the multivesicular body sorting pathway is
      supported as part of the core ESCRT-I endosomal cargo-sorting role.
    action: ACCEPT
    reason: TSG101/ESCRT-I sorts ubiquitinated endocytic cargo into MVBs and thereby supports
      endosome-to-lysosome/vacuolar delivery of cargo.
    additional_reference_ids:
    - PMID:11595185
    - PMID:12900395
    - file:human/TSG101/TSG101-uniprot.txt
    - file:human/TSG101/TSG101-notes.md
    supported_by: *id004
- term:
    id: GO:0031625
    label: ubiquitin protein ligase binding
  evidence_type: IPI
  original_reference_id: PMID:17229889
  qualifier: enables
  review:
    summary: Ubiquitin ligase binding is supported as regulatory context but not core.
    action: KEEP_AS_NON_CORE
    reason: TSG101 interacts with LRSAM1/MGRN1 and can be monoubiquitinated, but this regulatory binding is
      secondary to ESCRT-I cargo sorting.
    additional_reference_ids: *id003
    supported_by:
    - reference_id: file:human/TSG101/TSG101-uniprot.txt
      supporting_text: Interacts with LRSAM1
    - reference_id: file:human/TSG101/TSG101-uniprot.txt
      supporting_text: Interacts with MGRN1
    - reference_id: file:human/TSG101/TSG101-uniprot.txt
      supporting_text: Monoubiquitinated at multiple sites by LRSAM1 and by MGRN1
- term:
    id: GO:0005769
    label: early endosome
  evidence_type: IDA
  original_reference_id: PMID:17229889
  qualifier: located_in
  review:
    summary: early endosome localization is supported and relevant to ESCRT-I cargo sorting.
    action: ACCEPT
    reason: TSG101 cycles between cytosol and active endosomal membranes, including early/late endosome and
      MVB contexts where ESCRT-I functions.
    additional_reference_ids:
    - PMID:12900395
    - file:human/TSG101/TSG101-uniprot.txt
    - file:human/TSG101/TSG101-notes.md
    supported_by: *id005
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:18256029
  qualifier: enables
  review:
    summary: protein binding is too generic to represent TSG101 function.
    action: MARK_AS_OVER_ANNOTATED
    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.
    additional_reference_ids: *id001
    supported_by:
    - *id006
    - *id007
    - *id008
    - *id009
    - *id010
    - *id011
    - *id012
    - *id013
    proposed_replacement_terms: *id014
- term:
    id: GO:0048306
    label: calcium-dependent protein binding
  evidence_type: IPI
  original_reference_id: PMID:19520058
  qualifier: enables
  review:
    summary: calcium-dependent protein binding is too generic to represent TSG101 function.
    action: MARK_AS_OVER_ANNOTATED
    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.
    additional_reference_ids: *id001
    supported_by:
    - *id006
    - *id007
    - *id008
    - *id009
    - *id010
    - *id011
    - *id012
    - *id013
    proposed_replacement_terms: *id014
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:18077552
  qualifier: enables
  review:
    summary: protein binding is too generic to represent TSG101 function.
    action: MARK_AS_OVER_ANNOTATED
    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.
    additional_reference_ids: *id001
    supported_by:
    - *id006
    - *id007
    - *id008
    - *id009
    - *id010
    - *id011
    - *id012
    - *id013
    proposed_replacement_terms: *id014
- term:
    id: GO:0005737
    label: cytoplasm
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  qualifier: located_in
  review:
    summary: cytoplasm localization is supported but is not the core proteostasis annotation.
    action: KEEP_AS_NON_CORE
    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.
    additional_reference_ids: *id003
    supported_by:
    - reference_id: file:human/TSG101/TSG101-uniprot.txt
      supporting_text: Mainly cytoplasmic
    - reference_id: file:human/TSG101/TSG101-uniprot.txt
      supporting_text: Nuclear localization is cell cycle-dependent
    - reference_id: file:human/TSG101/TSG101-uniprot.txt
      supporting_text: localization to the midbody during cytokinesis
- term:
    id: GO:0005737
    label: cytoplasm
  evidence_type: IDA
  original_reference_id: PMID:18077552
  qualifier: located_in
  review:
    summary: cytoplasm localization is supported but is not the core proteostasis annotation.
    action: KEEP_AS_NON_CORE
    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.
    additional_reference_ids: *id003
    supported_by:
    - reference_id: file:human/TSG101/TSG101-uniprot.txt
      supporting_text: Mainly cytoplasmic
    - reference_id: file:human/TSG101/TSG101-uniprot.txt
      supporting_text: Nuclear localization is cell cycle-dependent
    - reference_id: file:human/TSG101/TSG101-uniprot.txt
      supporting_text: localization to the midbody during cytokinesis
- term:
    id: GO:0046755
    label: viral budding
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  qualifier: involved_in
  review:
    summary: viral budding is supported but reflects host-pathogen exploitation of ESCRT-I.
    action: KEEP_AS_NON_CORE
    reason: Viral budding/release annotations are well supported for TSG101 but are non-core for the human
      proteostasis-network review.
    additional_reference_ids: *id015
    supported_by: *id016
- term:
    id: GO:0005770
    label: late endosome
  evidence_type: IMP
  original_reference_id: PMID:15126635
  qualifier: located_in
  review:
    summary: late endosome localization is supported and relevant to ESCRT-I cargo sorting.
    action: ACCEPT
    reason: TSG101 cycles between cytosol and active endosomal membranes, including early/late endosome and
      MVB contexts where ESCRT-I functions.
    additional_reference_ids:
    - PMID:12900395
    - file:human/TSG101/TSG101-uniprot.txt
    - file:human/TSG101/TSG101-notes.md
    supported_by: *id005
- term:
    id: GO:0046755
    label: viral budding
  evidence_type: IMP
  original_reference_id: PMID:15126635
  qualifier: involved_in
  review:
    summary: viral budding is supported but reflects host-pathogen exploitation of ESCRT-I.
    action: KEEP_AS_NON_CORE
    reason: Viral budding/release annotations are well supported for TSG101 but are non-core for the human
      proteostasis-network review.
    additional_reference_ids: *id015
    supported_by: *id016
- term:
    id: GO:0005771
    label: multivesicular body
  evidence_type: TAS
  original_reference_id: PMID:15611048
  qualifier: located_in
  review:
    summary: multivesicular body localization is supported and relevant to ESCRT-I cargo sorting.
    action: ACCEPT
    reason: TSG101 cycles between cytosol and active endosomal membranes, including early/late endosome and
      MVB contexts where ESCRT-I functions.
    additional_reference_ids:
    - PMID:12900395
    - file:human/TSG101/TSG101-uniprot.txt
    - file:human/TSG101/TSG101-notes.md
    supported_by: *id005
- term:
    id: GO:0043130
    label: ubiquitin binding
  evidence_type: TAS
  original_reference_id: PMID:15611048
  qualifier: enables
  review:
    summary: Ubiquitin binding is a core TSG101 UEV-domain molecular function.
    action: ACCEPT
    reason: TSG101 binds ubiquitin/ubiquitinated cargo through its UEV domain and uses that activity in
      ESCRT-I cargo sorting and PTAP-motif recruitment contexts.
    additional_reference_ids:
    - PMID:11595185
    - file:human/TSG101/TSG101-uniprot.txt
    - file:human/TSG101/TSG101-notes.md
    supported_by: *id021
- term:
    id: GO:0043162
    label: ubiquitin-dependent protein catabolic process via the multivesicular body sorting pathway
  evidence_type: IDA
  original_reference_id: PMID:15611048
  qualifier: involved_in
  review:
    summary: ubiquitin-dependent protein catabolic process via the multivesicular body sorting pathway is
      supported as part of the core ESCRT-I endosomal cargo-sorting role.
    action: ACCEPT
    reason: TSG101/ESCRT-I sorts ubiquitinated endocytic cargo into MVBs and thereby supports
      endosome-to-lysosome/vacuolar delivery of cargo.
    additional_reference_ids:
    - PMID:11595185
    - PMID:12900395
    - file:human/TSG101/TSG101-uniprot.txt
    - file:human/TSG101/TSG101-notes.md
    supported_by: *id004
- term:
    id: GO:0003677
    label: DNA binding
  evidence_type: TAS
  original_reference_id: PMID:10888872
  qualifier: enables
  review:
    summary: DNA binding is a legacy/non-core nuclear transcription annotation and likely overstates the
      current functional picture.
    action: MARK_AS_OVER_ANNOTATED
    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.
    additional_reference_ids: *id003
    supported_by:
    - reference_id: file:human/TSG101/TSG101-uniprot.txt
      supporting_text: May be involved in cell growth and differentiation
    - reference_id: file:human/TSG101/TSG101-uniprot.txt
      supporting_text: Acts as a negative growth regulator
- term:
    id: GO:0003714
    label: transcription corepressor activity
  evidence_type: TAS
  original_reference_id: PMID:10888872
  qualifier: enables
  review:
    summary: transcription corepressor activity is a legacy/non-core nuclear transcription annotation and
      likely overstates the current functional picture.
    action: MARK_AS_OVER_ANNOTATED
    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.
    additional_reference_ids: *id003
    supported_by:
    - reference_id: file:human/TSG101/TSG101-uniprot.txt
      supporting_text: May be involved in cell growth and differentiation
    - reference_id: file:human/TSG101/TSG101-uniprot.txt
      supporting_text: Acts as a negative growth regulator
- term:
    id: GO:0000045
    label: autophagosome assembly
  evidence_type: IMP
  original_reference_id: PMID:31519728
  qualifier: involved_in
  review:
    summary: TSG101 should be added to autophagosome assembly for the ESCRT-I phagophore-closure role.
    action: NEW
    reason: The PN leaf is autophagophore sealing, and mammalian evidence shows core ESCRT-I components
      including TSG101 are required for autophagosome completion/phagophore closure.
    additional_reference_ids: *id018
    supported_by: *id019
references:
- id: GO_REF:0000002
  title: Gene Ontology annotation through association of InterPro records with GO terms
  findings: []
- id: GO_REF:0000024
  title: Manual transfer of experimentally-verified manual GO annotation data to orthologs by curator judgment
    of sequence similarity
  findings: []
- id: GO_REF:0000033
  title: Annotation inferences using phylogenetic trees
  findings: []
- id: GO_REF:0000044
  title: Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular Location vocabulary mapping,
    accompanied by conservative changes to GO terms applied by UniProt
  findings: []
- id: GO_REF:0000052
  title: Gene Ontology annotation based on curation of immunofluorescence data
  findings: []
- id: GO_REF:0000107
  title: Automatic transfer of experimentally verified manual GO annotation data to orthologs using Ensembl
    Compara
  findings: []
- id: GO_REF:0000108
  title: Automatic assignment of GO terms using logical inference, based on on inter-ontology links
  findings: []
- id: GO_REF:0000117
  title: Electronic Gene Ontology annotations created by ARBA machine learning models
  findings: []
- id: GO_REF:0000120
  title: Combined Automated Annotation using Multiple IEA Methods
  findings: []
- id: PMID:10888872
  title: DNMT1 binds HDAC2 and a new co-repressor, DMAP1, to form a complex at replication foci.
  findings: []
- id: PMID:11595185
  title: Tsg101 and the vacuolar protein sorting pathway are essential for HIV-1 budding.
  findings: []
- id: PMID:11916981
  title: Mammalian class E vps proteins recognize ubiquitin and act in the removal of endosomal
    protein-ubiquitin conjugates.
  findings: []
- id: PMID:12802020
  title: TSG101 interaction with HRS mediates endosomal trafficking and receptor down-regulation.
  findings: []
- id: PMID:12900395
  title: Hrs regulates multivesicular body formation via ESCRT recruitment to endosomes.
  findings: []
- id: PMID:14505570
  title: The protein network of HIV budding.
  findings: []
- id: PMID:14519844
  title: Divergent retroviral late-budding domains recruit vacuolar protein sorting factors by using
    alternative adaptor proteins.
  findings: []
- id: PMID:15033475
  title: Physical and functional interactions between Daxx and TSG101.
  findings: []
- id: PMID:15126635
  title: Nedd4.1-mediated ubiquitination and subsequent recruitment of Tsg101 ensure HTLV-1 Gag trafficking
    towards the multivesicular body pathway prior to virus budding.
  findings: []
- id: PMID:15218037
  title: The human endosomal sorting complex required for transport (ESCRT-I) and its role in HIV-1 budding.
  findings: []
- id: PMID:15326289
  title: Identification and proteomic profiling of exosomes in human urine.
  findings: []
- id: PMID:15611048
  title: Interactions of TOM1L1 with the multivesicular body sorting machinery.
  findings: []
- id: PMID:16118794
  title: 'SIMPLE interacts with NEDD4 and TSG101: evidence for a role in lysosomal sorting and implications for
    Charcot-Marie-Tooth disease.'
  findings: []
- id: PMID:16189514
  title: Towards a proteome-scale map of the human protein-protein interaction network.
  findings: []
- id: PMID:16501490
  title: Collection, storage, preservation, and normalization of human urinary exosomes for biomarker
    discovery.
  findings: []
- id: PMID:16554368
  title: The ESCRT-III subunit hVps24 is required for degradation but not silencing of the epidermal growth
    factor receptor.
  findings: []
- id: PMID:16973552
  title: Human ESCRT-II complex and its role in human immunodeficiency virus type 1 release.
  findings: []
- id: PMID:17174262
  title: HD-PTP and Alix share some membrane-traffic related proteins that interact with their Bro1 domains or
    proline-rich regions.
  findings: []
- id: PMID:17229889
  title: Spongiform neurodegeneration-associated E3 ligase Mahogunin ubiquitylates TSG101 and regulates
    endosomal trafficking.
  findings: []
- id: PMID:17350572
  title: Structural and biochemical studies of ALIX/AIP1 and its role in retrovirus budding.
  findings: []
- id: PMID:17714434
  title: Vps22/EAP30 in ESCRT-II mediates endosomal sorting of growth factor and chemokine receptors destined
    for lysosomal degradation.
  findings: []
- id: PMID:17853893
  title: Human ESCRT and ALIX proteins interact with proteins of the midbody and function in cytokinesis.
  findings: []
- id: PMID:17940959
  title: Involvement of vacuolar protein sorting pathway in Ebola virus release independent of TSG101
    interaction.
  findings: []
- id: PMID:18005716
  title: Identification of human MVB12 proteins as ESCRT-I subunits that function in HIV budding.
  findings: []
- id: PMID:18077552
  title: 'Regulation of Tsg101 expression by the steadiness box: a role of Tsg101-associated ligase.'
  findings: []
- id: PMID:18256029
  title: 'Identification of Alix-type and Non-Alix-type ALG-2-binding sites in human phospholipid scramblase 3:
    differential binding to an alternatively spliced isoform and amino acid-substituted mutants.'
  findings: []
- id: PMID:18641129
  title: Differential requirements for Alix and ESCRT-III in cytokinesis and HIV-1 release.
  findings: []
- id: PMID:19056867
  title: Large-scale proteomics and phosphoproteomics of urinary exosomes.
  findings: []
- id: PMID:19060904
  title: An empirical framework for binary interactome mapping.
  findings: []
- id: PMID:19520058
  title: Penta-EF-hand protein ALG-2 functions as a Ca2+-dependent adaptor that bridges Alix and TSG101.
  findings: []
- id: PMID:19549727
  title: Analysis of the human E2 ubiquitin conjugating enzyme protein interaction network.
  findings: []
- id: PMID:20176808
  title: TEX14 interacts with CEP55 to block cell abscission.
  findings: []
- id: PMID:20588296
  title: 'Membrane budding and scission by the ESCRT machinery: it''s all in the neck.'
  findings: []
- id: PMID:20654576
  title: Distinct functions of human MVB12A and MVB12B in the ESCRT-I dependent on their posttranslational
    modifications.
  findings: []
- id: PMID:21118109
  title: The role of ESCRT proteins in fusion events involving lysosomes, endosomes and autophagosomes.
  findings: []
- id: PMID:21757351
  title: UBAP1 is a component of an endosome-specific ESCRT-I complex that is essential for MVB sorting.
  findings: []
- id: PMID:22232651
  title: Structural basis for membrane targeting by the MVB12-associated β-prism domain of the human ESCRT-I
    MVB12 subunit.
  findings: []
- id: PMID:22315426
  title: Formation and release of arrestin domain-containing protein 1-mediated microvesicles (ARMMs) at
    plasma membrane by recruitment of TSG101 protein.
  findings: []
- id: PMID:22660413
  title: Syndecan-syntenin-ALIX regulates the biogenesis of exosomes.
  findings: []
- id: PMID:23092844
  title: Monitoring the Rab27 associated exosome pathway using nanoparticle tracking analysis.
  findings: []
- id: PMID:23166352
  title: Charcot-Marie-Tooth disease-linked protein SIMPLE functions with the ESCRT machinery in endosomal
    trafficking.
  findings: []
- id: PMID:23533145
  title: In-depth proteomic analyses of exosomes isolated from expressed prostatic secretions in urine.
  findings: []
- id: PMID:24105262
  title: Analysis of ESCRT functions in exosome biogenesis, composition and secretion highlights the
    heterogeneity of extracellular vesicles.
  findings: []
- id: PMID:25416956
  title: A proteome-scale map of the human interactome network.
  findings: []
- id: PMID:26871637
  title: Widespread Expansion of Protein Interaction Capabilities by Alternative Splicing.
  findings: []
- id: PMID:27107012
  title: Pooled-matrix protein interaction screens using Barcode Fusion Genetics.
  findings: []
- id: PMID:28514442
  title: Architecture of the human interactome defines protein communities and disease networks.
  findings: []
- id: PMID:31515488
  title: Extensive disruption of protein interactions by genetic variants across the allele frequency spectrum
    in human populations.
  findings: []
- id: PMID:32296183
  title: A reference map of the human binary protein interactome.
  findings: []
- id: PMID:32424346
  title: A helical assembly of human ESCRT-I scaffolds reverse-topology membrane scission.
  findings: []
- id: PMID:33961781
  title: Dual proteome-scale networks reveal cell-specific remodeling of the human interactome.
  findings: []
- id: PMID:35044719
  title: Proteome-scale mapping of binding sites in the unstructured regions of the human proteome.
  findings: []
- id: PMID:35271311
  title: 'OpenCell: Endogenous tagging for the cartography of human cellular organization.'
  findings: []
- id: PMID:37100772
  title: Large-scale phage-based screening reveals extensive pan-viral mimicry of host short linear motifs.
  findings: []
- id: PMID:37219487
  title: Large-scale phosphomimetic screening identifies phospho-modulated motif-based protein interactions.
  findings: []
- id: PMID:39526800
  title: A comprehensive two-hybrid analysis to explore the Legionella pneumophila effector-effector
    interactome.
  findings: []
- id: PMID:40205054
  title: Multimodal cell maps as a foundation for structural and functional genomics.
  findings: []
- id: PMID:9241264
  title: TSG101 may be the prototype of a class of dominant negative ubiquitin regulators.
  findings: []
- id: Reactome:R-HSA-184269
  title: Monoubiquitinated N-myristoyl GAG polyprotein is targeted to the late endosomal vesicle membrane by
    the ESCRT-I complex
  findings: []
- id: Reactome:R-HSA-3149434
  title: Transport of GAG to the Plasma Membrane
  findings: []
- id: Reactome:R-HSA-3159232
  title: Recruitment Of HIV Virion Budding Machinery
  findings: []
- id: Reactome:R-HSA-917696
  title: Cargo Sequestration
  findings: []
- id: Reactome:R-HSA-917730
  title: Cargo Recognition And Sorting
  findings: []
- id: PMID:31010855
  title: Rab5-dependent autophagosome closure by ESCRT.
  findings: []
- id: PMID:31519728
  title: VPS37A directs ESCRT recruitment for phagophore closure.
  findings: []
- id: file:human/TSG101/TSG101-uniprot.txt
  title: UniProtKB record for human TSG101
  findings: []
- id: file:human/TSG101/TSG101-notes.md
  title: TSG101 review notes
  findings: []
core_functions:
- molecular_function:
    id: GO:0043130
    label: ubiquitin binding
  description: 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.
  directly_involved_in:
  - id: GO:0043162
    label: ubiquitin-dependent protein catabolic process via the multivesicular body sorting pathway
  - id: GO:0036258
    label: multivesicular body assembly
  - id: GO:0090148
    label: membrane fission
  - id: GO:0000045
    label: autophagosome assembly
  locations:
  - id: GO:0010008
    label: endosome membrane
  - id: GO:0031901
    label: early endosome membrane
  - id: GO:0031902
    label: late endosome membrane
  in_complex:
    id: GO:0000813
    label: ESCRT I complex
  supported_by:
  - *id006
  - *id007
  - *id008
  - *id009
  - *id010
  - *id011
  - *id012
  - *id013
  - *id022
  - *id023
  - *id024
  - *id025
  - *id026
  - *id027
  - *id028
  - *id029
  - *id030
  - *id031
  - *id032
  - *id033
  - *id034
proposed_new_terms: []
suggested_questions:
- question: Should the TSG101 autophagy annotation be changed from broad macroautophagy/autophagosome
    maturation to GO:0000045 autophagosome assembly for phagophore closure?
  experts:
  - GO autophagy editors
  - GO ESCRT curators
- question: Should generic TSG101 protein-binding annotations be retired in favor of ubiquitin binding,
    ESCRT-I complex membership, and specific pathway contexts?
  experts:
  - GO molecular function editors
  - UniProt curators
- question: Should viral budding, cytokinesis, and exosome annotations remain non-core branches in
    proteostasis-focused TSG101 curation?
  experts:
  - GO viral process editors
  - GO cell-cycle editors
  - GO extracellular vesicle editors
suggested_experiments:
- experiment_type: TSG101 separation-of-function phagophore closure rescue
  hypothesis: TSG101 UEV-domain ubiquitin/PTAP-motif binding and ESCRT-I assembly surfaces make separable
    contributions to phagophore closure and MVB cargo sorting.
  description: 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.
- experiment_type: endogenous ESCRT-I autophagy recruitment imaging
  hypothesis: Core ESCRT-I components including TSG101 transiently localize to closing LC3-positive
    phagophores before ESCRT-III/VPS4 recruitment.
  description: Endogenously tag TSG101, VPS28, VPS37A, CHMP2A, and LC3 reporters and quantify recruitment
    order during starvation-induced phagophore closure.