id: A5D8V6
gene_symbol: VPS37C
product_type: PROTEIN
status: COMPLETE
taxon:
  id: NCBITaxon:9606
  label: Homo sapiens
description: VPS37C is a VPS37-family ESCRT-I subunit that complexes with TSG101, VPS28, and MVB12/UBAP-family partners. The
  best-supported cellular function is ESCRT-I-dependent endosomal sorting of ubiquitinated cargo into multivesicular bodies,
  with late-endosome/endosome-membrane localization and a secondary viral budding context. Current local evidence does not
  support transferring the VPS37A-specific phagophore-closure role to VPS37C as a core annotation.
existing_annotations:
- term:
    id: GO:0043162
    label: ubiquitin-dependent protein catabolic process via the multivesicular body sorting pathway
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: involved_in
  review:
    summary: ubiquitin-dependent protein catabolic process via the multivesicular body sorting pathway is supported as part
      of the core VPS37C/ESCRT-I endosomal cargo-sorting role.
    action: ACCEPT
    reason: VPS37C/ESCRT-I supports ubiquitin-dependent endosomal cargo sorting into multivesicular bodies.
    additional_reference_ids: &id001
    - PMID:15509564
    - PMID:18005716
    - file:human/VPS37C/VPS37C-uniprot.txt
    - file:human/VPS37C/VPS37C-notes.md
    supported_by: &id002
    - &id028
      reference_id: file:human/VPS37C/VPS37C-uniprot.txt
      supporting_text: Required for the sorting of endocytic
    - &id029
      reference_id: file:human/VPS37C/VPS37C-uniprot.txt
      supporting_text: ubiquitinated cargos into multivesicular bodies
    - &id030
      reference_id: PMID:15509564
      supporting_text: required for the sorting of ubiquitinated transmembrane proteins into internal vesicles of multivesicular
        bodies
    - &id031
      reference_id: PMID:15509564
      supporting_text: binds to another class E VPS factor, namely Hrs
    - &id032
      reference_id: PMID:18005716
      supporting_text: plays essential roles in HIV budding and endosomal protein sorting
- term:
    id: GO:0000813
    label: ESCRT I complex
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: part_of
  review:
    summary: ESCRT-I complex membership is a central VPS37C cellular-component annotation.
    action: ACCEPT
    reason: VPS37C is a VPS37-family ESCRT-I subunit that complexes with TSG101, VPS28, and fourth-subunit partners.
    additional_reference_ids: &id003
    - PMID:15509564
    - PMID:18005716
    - PMID:22405001
    - file:human/VPS37C/VPS37C-uniprot.txt
    - file:human/VPS37C/VPS37C-notes.md
    supported_by: &id004
    - &id008
      reference_id: file:human/VPS37C/VPS37C-uniprot.txt
      supporting_text: Component of the ESCRT-I complex
    - &id009
      reference_id: file:human/VPS37C/VPS37C-uniprot.txt
      supporting_text: which consists of TSG101, VPS28, a VPS37
    - &id010
      reference_id: file:human/VPS37C/VPS37C-uniprot.txt
      supporting_text: Interacts with TSG101, VPS28, MVB12A and MVB12B
    - &id011
      reference_id: PMID:15509564
      supporting_text: VPS37C can form a ternary complex with Tsg101 and VPS28
    - &id012
      reference_id: PMID:15509564
      supporting_text: Thus, this study identifies VPS37C as a functional component of mammalian ESCRT-I
    - &id026
      reference_id: PMID:18005716
      supporting_text: All ESCRT-I complexes contain three common subunits (TSG101, VPS28, and VPS37)
    - &id027
      reference_id: PMID:22405001
      supporting_text: complex with Vps23/TSG101, VPS28, and VPS37
- term:
    id: GO:0006612
    label: protein targeting to membrane
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: involved_in
  review:
    summary: protein targeting to membrane is too broad for VPS37C ESCRT-I function.
    action: MODIFY
    reason: The supported process is ESCRT-I-dependent endosomal cargo sorting into the MVB pathway, not generic protein targeting.
    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
    additional_reference_ids: *id001
    supported_by: *id002
- term:
    id: GO:0006623
    label: protein targeting to vacuole
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: involved_in
  review:
    summary: protein targeting to vacuole is too broad for VPS37C ESCRT-I function.
    action: MODIFY
    reason: The supported process is ESCRT-I-dependent endosomal cargo sorting into the MVB pathway, not generic protein targeting.
    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
    additional_reference_ids: *id001
    supported_by: *id002
- 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 a central VPS37C cellular-component annotation.
    action: ACCEPT
    reason: VPS37C is a VPS37-family ESCRT-I subunit that complexes with TSG101, VPS28, and fourth-subunit partners.
    additional_reference_ids: *id003
    supported_by: *id004
- term:
    id: GO:0016236
    label: macroautophagy
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  qualifier: involved_in
  review:
    summary: Macroautophagy is over-annotated for VPS37C.
    action: MARK_AS_OVER_ANNOTATED
    reason: The accessible ESCRT autophagy evidence is broad or VPS37A-specific; there is not enough direct evidence to make
      VPS37C a phagophore-closure/autophagosome assembly factor.
    proposed_replacement_terms:
    - id: GO:0000813
      label: ESCRT I complex
    additional_reference_ids: &id016
    - PMID:20588296
    - PMID:31519728
    - PMID:32424346
    - file:human/VPS37C/VPS37C-notes.md
    supported_by: &id017
    - reference_id: PMID:20588296
      supporting_text: viral budding, cytokinesis and, probably, autophagy
    - reference_id: PMID:20588296
      supporting_text: direct neck closure reaction in autophagy
    - reference_id: PMID:31519728
      supporting_text: identify the ESCRT-I subunit VPS37A as a critical component
    - reference_id: PMID:31519728
      supporting_text: required for autophagosome completion
- 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 VPS37C/ESCRT-I function.
    action: ACCEPT
    reason: VPS37C is a peripheral late-endosome/endosome-membrane ESCRT-I component recruited to aberrant endosomes in ESCRT
      perturbation assays.
    additional_reference_ids: &id024
    - PMID:15509564
    - file:human/VPS37C/VPS37C-uniprot.txt
    - file:human/VPS37C/VPS37C-notes.md
    supported_by: &id025
    - &id013
      reference_id: file:human/VPS37C/VPS37C-uniprot.txt
      supporting_text: Late endosome membrane
    - &id014
      reference_id: file:human/VPS37C/VPS37C-uniprot.txt
      supporting_text: Probably associates with membranes
    - &id015
      reference_id: PMID:15509564
      supporting_text: VPS37C is recruited to aberrant endosomes
- 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 VPS37C/ESCRT-I endosomal cargo-sorting role.
    action: ACCEPT
    reason: VPS37C/ESCRT-I supports ubiquitin-dependent endosomal cargo sorting into multivesicular bodies.
    additional_reference_ids: *id001
    supported_by: *id002
- term:
    id: GO:0039702
    label: viral budding via host ESCRT complex
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  qualifier: involved_in
  review:
    summary: Viral budding via host ESCRT complex is supported as a secondary context but is not the core VPS37C proteostasis
      function.
    action: KEEP_AS_NON_CORE
    reason: VPS37C can support ESCRT-I-dependent viral budding, but the core cellular role is endosomal ESCRT-I cargo sorting.
    additional_reference_ids: &id018
    - PMID:15509564
    - PMID:18005716
    - PMID:20588296
    - file:human/VPS37C/VPS37C-uniprot.txt
    - file:human/VPS37C/VPS37C-notes.md
    supported_by: &id019
    - reference_id: PMID:15509564
      supporting_text: VPS37C is recruited to the plasma membrane
    - reference_id: PMID:15509564
      supporting_text: direct fusion of VPS37C to HIV-1 Gag
    - reference_id: PMID:15509564
      supporting_text: inhibited by VPS37C depletion
    - reference_id: PMID:18005716
      supporting_text: plays essential roles in HIV budding and endosomal protein sorting
    - reference_id: PMID:20588296
      supporting_text: viral budding, cytokinesis and, probably, autophagy
- term:
    id: GO:0048306
    label: calcium-dependent protein binding
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  qualifier: enables
  review:
    summary: Calcium-dependent protein binding is supported but secondary.
    action: KEEP_AS_NON_CORE
    reason: VPS37C participates in an ALG-2/ALIX/ESCRT-I calcium-dependent ternary-complex context, but this is not the core
      VPS37C proteostasis function.
    additional_reference_ids: &id020
    - PMID:23924735
    - file:human/VPS37C/VPS37C-notes.md
    supported_by: &id021
    - reference_id: PMID:23924735
      supporting_text: VPS37B and VPS37C appeared to interact with ALG-2
    - reference_id: PMID:23924735
      supporting_text: adaptor protein that bridges ALIX and ESCRT-I
- 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 VPS37C function.
    action: MARK_AS_OVER_ANNOTATED
    reason: The informative annotations are ESCRT-I complex membership, endosomal MVB sorting, and specific ESCRT-I interaction
      contexts, not generic protein binding from interaction assays or screens.
    proposed_replacement_terms: &id005
    - id: GO:0000813
      label: ESCRT I complex
    additional_reference_ids: &id006
    - PMID:15509564
    - PMID:17853893
    - PMID:25416956
    - PMID:31515488
    - PMID:32296183
    - PMID:35271311
    - file:human/VPS37C/VPS37C-notes.md
    supported_by: &id007
    - reference_id: PMID:15509564
      supporting_text: VPS37C can form a ternary complex with Tsg101 and VPS28
    - reference_id: file:human/VPS37C/VPS37C-notes.md
      supporting_text: Generic `protein binding` rows are over-annotated
- 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 VPS37C function.
    action: MARK_AS_OVER_ANNOTATED
    reason: The informative annotations are ESCRT-I complex membership, endosomal MVB sorting, and specific ESCRT-I interaction
      contexts, not generic protein binding from interaction assays or screens.
    proposed_replacement_terms: *id005
    additional_reference_ids: *id006
    supported_by: *id007
- 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 VPS37C function.
    action: MARK_AS_OVER_ANNOTATED
    reason: The informative annotations are ESCRT-I complex membership, endosomal MVB sorting, and specific ESCRT-I interaction
      contexts, not generic protein binding from interaction assays or screens.
    proposed_replacement_terms: *id005
    additional_reference_ids: *id006
    supported_by: *id007
- 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 VPS37C function.
    action: MARK_AS_OVER_ANNOTATED
    reason: The informative annotations are ESCRT-I complex membership, endosomal MVB sorting, and specific ESCRT-I interaction
      contexts, not generic protein binding from interaction assays or screens.
    proposed_replacement_terms: *id005
    additional_reference_ids: *id006
    supported_by: *id007
- 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 VPS37C function.
    action: MARK_AS_OVER_ANNOTATED
    reason: The informative annotations are ESCRT-I complex membership, endosomal MVB sorting, and specific ESCRT-I interaction
      contexts, not generic protein binding from interaction assays or screens.
    proposed_replacement_terms: *id005
    additional_reference_ids: *id006
    supported_by: *id007
- term:
    id: GO:0005654
    label: nucleoplasm
  evidence_type: IDA
  original_reference_id: GO_REF:0000052
  qualifier: located_in
  review:
    summary: Nucleoplasm localization is not part of the core VPS37C ESCRT-I function.
    action: KEEP_AS_NON_CORE
    reason: The core supported localization is late endosome/endosome membrane; the nucleoplasm row comes from high-throughput
      localization mapping and should not drive the functional model.
    additional_reference_ids:
    - file:human/VPS37C/VPS37C-notes.md
    supported_by:
    - reference_id: file:human/VPS37C/VPS37C-notes.md
      supporting_text: Extracellular exosome and nucleoplasm rows come from high-throughput localization/proteomics and should
        remain non-core
- 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 a central VPS37C cellular-component annotation.
    action: ACCEPT
    reason: VPS37C is a VPS37-family ESCRT-I subunit that complexes with TSG101, VPS28, and fourth-subunit partners.
    additional_reference_ids: *id003
    supported_by: *id004
- 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 correct for VPS37C, but PMID:21757351 is not the strongest VPS37C-specific support.
    action: ACCEPT
    reason: The term is correct from VPS37C-specific and shared ESCRT-I evidence; however, PMID:21757351 specifically defines
      a UBAP1/VPS37A endosome-specific complex and says it does not contain VPS37C.
    additional_reference_ids:
    - PMID:15509564
    - PMID:18005716
    - PMID:21757351
    - file:human/VPS37C/VPS37C-uniprot.txt
    - file:human/VPS37C/VPS37C-notes.md
    supported_by:
    - *id008
    - *id009
    - *id010
    - *id011
    - *id012
    - reference_id: PMID:21757351
      supporting_text: contains VPS37A but not VPS37C
- term:
    id: GO:0010008
    label: endosome membrane
  evidence_type: NAS
  original_reference_id: PMID:32424346
  qualifier: located_in
  review:
    summary: endosome membrane is correct for VPS37C, but PMID:32424346 is indirect for this isoform.
    action: ACCEPT
    reason: Endosome-membrane localization is supported by VPS37C-specific evidence; PMID:32424346 supports general ESCRT-I
      mechanism using a VPS37B-containing headpiece.
    additional_reference_ids:
    - PMID:15509564
    - PMID:32424346
    - file:human/VPS37C/VPS37C-uniprot.txt
    - file:human/VPS37C/VPS37C-notes.md
    supported_by:
    - *id013
    - *id014
    - *id015
    - reference_id: PMID:32424346
      supporting_text: comprising TSG101-VPS28-VPS37B-MVB12A
- 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 VPS37C/ESCRT-I endosomal cargo-sorting role.
    action: ACCEPT
    reason: VPS37C/ESCRT-I supports ubiquitin-dependent endosomal cargo sorting into multivesicular bodies.
    additional_reference_ids: *id001
    supported_by: *id002
- 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 VPS37C/ESCRT-I endosomal cargo-sorting role.
    action: ACCEPT
    reason: VPS37C/ESCRT-I supports ubiquitin-dependent endosomal cargo sorting into multivesicular bodies.
    additional_reference_ids: *id001
    supported_by: *id002
- term:
    id: GO:0090148
    label: membrane fission
  evidence_type: NAS
  original_reference_id: PMID:32424346
  qualifier: involved_in
  review:
    summary: Membrane fission is a broad ESCRT-I mechanism annotation and is over-transferred for VPS37C as written.
    action: MARK_AS_OVER_ANNOTATED
    reason: The cited structural/autophagy work directly tested a VPS37B-containing headpiece and VPS28 interface mutants,
      not VPS37C; the safer VPS37C annotations are ESCRT-I complex and MVB sorting.
    proposed_replacement_terms:
    - id: GO:0000813
      label: ESCRT I complex
    - id: GO:0036258
      label: multivesicular body assembly
    additional_reference_ids:
    - PMID:32424346
    - PMID:15509564
    - file:human/VPS37C/VPS37C-notes.md
    supported_by:
    - reference_id: PMID:32424346
      supporting_text: comprising TSG101-VPS28-VPS37B-MVB12A
    - reference_id: PMID:32424346
      supporting_text: ESCRT-I is not merely a bridging adaptor
    - reference_id: PMID:15509564
      supporting_text: functional component of mammalian ESCRT-I
- term:
    id: GO:0016236
    label: macroautophagy
  evidence_type: TAS
  original_reference_id: PMID:20588296
  qualifier: involved_in
  review:
    summary: Macroautophagy is over-annotated for VPS37C.
    action: MARK_AS_OVER_ANNOTATED
    reason: The accessible ESCRT autophagy evidence is broad or VPS37A-specific; there is not enough direct evidence to make
      VPS37C a phagophore-closure/autophagosome assembly factor.
    proposed_replacement_terms:
    - id: GO:0000813
      label: ESCRT I complex
    additional_reference_ids: *id016
    supported_by: *id017
- 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 a central VPS37C cellular-component annotation.
    action: ACCEPT
    reason: VPS37C is a VPS37-family ESCRT-I subunit that complexes with TSG101, VPS28, and fourth-subunit partners.
    additional_reference_ids: *id003
    supported_by: *id004
- 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 VPS37C/ESCRT-I endosomal cargo-sorting role.
    action: ACCEPT
    reason: VPS37C/ESCRT-I supports ubiquitin-dependent endosomal cargo sorting into multivesicular bodies.
    additional_reference_ids: *id001
    supported_by: *id002
- term:
    id: GO:0039702
    label: viral budding via host ESCRT complex
  evidence_type: TAS
  original_reference_id: PMID:20588296
  qualifier: involved_in
  review:
    summary: Viral budding via host ESCRT complex is supported as a secondary context but is not the core VPS37C proteostasis
      function.
    action: KEEP_AS_NON_CORE
    reason: VPS37C can support ESCRT-I-dependent viral budding, but the core cellular role is endosomal ESCRT-I cargo sorting.
    additional_reference_ids: *id018
    supported_by: *id019
- 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 a central VPS37C cellular-component annotation.
    action: ACCEPT
    reason: VPS37C is a VPS37-family ESCRT-I subunit that complexes with TSG101, VPS28, and fourth-subunit partners.
    additional_reference_ids: *id003
    supported_by: *id004
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:23924735
  qualifier: enables
  review:
    summary: Protein binding is too generic to represent VPS37C function.
    action: MARK_AS_OVER_ANNOTATED
    reason: The informative annotations are ESCRT-I complex membership, endosomal MVB sorting, and specific ESCRT-I interaction
      contexts, not generic protein binding from interaction assays or screens.
    proposed_replacement_terms:
    - id: GO:0048306
      label: calcium-dependent protein binding
    additional_reference_ids: *id020
    supported_by: *id021
- term:
    id: GO:0048306
    label: calcium-dependent protein binding
  evidence_type: IPI
  original_reference_id: PMID:23924735
  qualifier: enables
  review:
    summary: Calcium-dependent protein binding is supported but secondary.
    action: KEEP_AS_NON_CORE
    reason: VPS37C participates in an ALG-2/ALIX/ESCRT-I calcium-dependent ternary-complex context, but this is not the core
      VPS37C proteostasis function.
    additional_reference_ids: *id020
    supported_by: *id021
- term:
    id: GO:0070062
    label: extracellular exosome
  evidence_type: HDA
  original_reference_id: PMID:23533145
  qualifier: located_in
  review:
    summary: Extracellular exosome is a high-throughput proteomics/localization context and not a core VPS37C annotation.
    action: KEEP_AS_NON_CORE
    reason: Exosome detection is not the central VPS37C ESCRT-I endosomal sorting function.
    additional_reference_ids: &id022
    - PMID:19056867
    - PMID:23533145
    - file:human/VPS37C/VPS37C-notes.md
    supported_by: &id023
    - reference_id: PMID:19056867
      supporting_text: Large-scale proteomics and phosphoproteomics of urinary exosomes
    - reference_id: PMID:23533145
      supporting_text: In-depth proteomic analyses of exosomes
- term:
    id: GO:0070062
    label: extracellular exosome
  evidence_type: HDA
  original_reference_id: PMID:19056867
  qualifier: located_in
  review:
    summary: Extracellular exosome is a high-throughput proteomics/localization context and not a core VPS37C annotation.
    action: KEEP_AS_NON_CORE
    reason: Exosome detection is not the central VPS37C ESCRT-I endosomal sorting function.
    additional_reference_ids: *id022
    supported_by: *id023
- term:
    id: GO:0000813
    label: ESCRT I complex
  evidence_type: IDA
  original_reference_id: PMID:22405001
  qualifier: part_of
  review:
    summary: ESCRT-I complex membership is a central VPS37C cellular-component annotation.
    action: ACCEPT
    reason: VPS37C is a VPS37-family ESCRT-I subunit that complexes with TSG101, VPS28, and fourth-subunit partners.
    additional_reference_ids: *id003
    supported_by: *id004
- term:
    id: GO:0010008
    label: endosome membrane
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-184269
  qualifier: located_in
  review:
    summary: endosome membrane localization is supported and relevant to VPS37C/ESCRT-I function.
    action: ACCEPT
    reason: VPS37C is a peripheral late-endosome/endosome-membrane ESCRT-I component recruited to aberrant endosomes in ESCRT
      perturbation assays.
    additional_reference_ids: *id024
    supported_by: *id025
- 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 VPS37C/ESCRT-I function.
    action: ACCEPT
    reason: VPS37C is a peripheral late-endosome/endosome-membrane ESCRT-I component recruited to aberrant endosomes in ESCRT
      perturbation assays.
    additional_reference_ids: *id024
    supported_by: *id025
- 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 VPS37C/ESCRT-I function.
    action: ACCEPT
    reason: VPS37C is a peripheral late-endosome/endosome-membrane ESCRT-I component recruited to aberrant endosomes in ESCRT
      perturbation assays.
    additional_reference_ids: *id024
    supported_by: *id025
- 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 VPS37C/ESCRT-I function.
    action: ACCEPT
    reason: VPS37C is a peripheral late-endosome/endosome-membrane ESCRT-I component recruited to aberrant endosomes in ESCRT
      perturbation assays.
    additional_reference_ids: *id024
    supported_by: *id025
- 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 VPS37C/ESCRT-I function.
    action: ACCEPT
    reason: VPS37C is a peripheral late-endosome/endosome-membrane ESCRT-I component recruited to aberrant endosomes in ESCRT
      perturbation assays.
    additional_reference_ids: *id024
    supported_by: *id025
references:
- 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:0000117
  title: Electronic Gene Ontology annotations created by ARBA machine learning models
  findings: []
- id: PMID:17853893
  title: Human ESCRT and ALIX proteins interact with proteins of the midbody and function in cytokinesis.
  findings: []
- id: PMID:18005716
  title: Identification of human MVB12 proteins as ESCRT-I subunits that function in HIV budding.
  findings: []
- id: PMID:19056867
  title: Large-scale proteomics and phosphoproteomics of urinary exosomes.
  findings: []
- id: PMID:20588296
  title: 'Membrane budding and scission by the ESCRT machinery: it''s all in the neck.'
  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:22405001
  title: The UBAP1 subunit of ESCRT-I interacts with ubiquitin via a SOUBA domain.
  findings: []
- id: PMID:23533145
  title: In-depth proteomic analyses of exosomes isolated from expressed prostatic secretions in urine.
  findings: []
- id: PMID:23924735
  title: VPS37 isoforms differentially modulate the ternary complex formation of ALIX, ALG-2, and ESCRT-I.
  findings: []
- id: PMID:25416956
  title: A proteome-scale map of the human interactome network.
  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:35271311
  title: 'OpenCell: Endogenous tagging for the cartography of human cellular organization.'
  findings: []
- id: Reactome:R-HSA-184269
  title: Monoubiquitinated N-myristoyl GAG polyprotein is targeted to the late endosomal vesicle membrane by the ESCRT-I complex
  findings: []
- id: Reactome:R-HSA-3149434
  title: Transport of GAG to the Plasma Membrane
  findings: []
- id: Reactome:R-HSA-3159232
  title: Recruitment Of HIV Virion Budding Machinery
  findings: []
- id: Reactome:R-HSA-917696
  title: Cargo Sequestration
  findings: []
- id: Reactome:R-HSA-917730
  title: Cargo Recognition And Sorting
  findings: []
- id: PMID:15509564
  title: Identification of human VPS37C, a component of endosomal sorting complex required for transport-I important for viral
    budding.
  findings: []
- id: PMID:31519728
  title: VPS37A directs ESCRT recruitment for phagophore closure.
  findings: []
- id: file:human/VPS37C/VPS37C-uniprot.txt
  title: UniProtKB record for human VPS37C
  findings: []
- id: file:human/VPS37C/VPS37C-notes.md
  title: VPS37C review notes
  findings: []
core_functions:
- description: VPS37C is a structural ESCRT-I subunit that helps organize TSG101-VPS28-VPS37-MVB12/UBAP-family complexes for
    ubiquitin-dependent endosomal cargo sorting and MVB assembly.
  directly_involved_in:
  - id: GO:0043162
    label: ubiquitin-dependent protein catabolic process via the multivesicular body sorting pathway
  - id: GO:0036258
    label: multivesicular body assembly
  locations:
  - id: GO:0010008
    label: endosome membrane
  - id: GO:0031902
    label: late endosome membrane
  in_complex:
    id: GO:0000813
    label: ESCRT I complex
  supported_by:
  - *id008
  - *id009
  - *id010
  - *id011
  - *id012
  - *id026
  - *id027
  - *id028
  - *id029
  - *id030
  - *id031
  - *id032
  - *id013
  - *id014
  - *id015
proposed_new_terms: []
suggested_questions:
- question: Should VPS37C macroautophagy annotations be retired or kept non-core given that the direct phagophore-closure
    evidence is VPS37A-specific?
  experts:
  - GO autophagy editors
  - GO ESCRT curators
- question: Should generic VPS37C protein-binding annotations be replaced by ESCRT-I complex membership, calcium-dependent
    ALG-2 interaction context, and specific endosomal sorting terms?
  experts:
  - GO molecular function editors
  - UniProt curators
suggested_experiments:
- experiment_type: VPS37 paralog phagophore closure comparison
  hypothesis: VPS37A, but not necessarily VPS37C, is the VPS37 paralog specialized for phagophore closure.
  description: Compare VPS37A, VPS37B, and VPS37C depletion/rescue in HT-LC3 autophagosome closure assays and parallel EGFR
    or tetherin MVB-sorting assays, using endogenous expression or matched rescue levels.
- experiment_type: VPS37C-specific MVB sorting assay
  hypothesis: VPS37C contributes to a subset of ESCRT-I cargo-sorting or viral-budding contexts distinct from the UBAP1/VPS37A
    endosome-specific complex.
  description: Use VPS37C-specific knockout-rescue with quantitative cargo degradation and HIV-1 Gag recruitment/release readouts,
    controlling for VPS37A and VPS37B compensation.
