VPS37C

UniProt ID: A5D8V6
Organism: Homo sapiens
Review Status: COMPLETE
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Gene 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 Review

GO Term Evidence Action Reason
GO:0043162 ubiquitin-dependent protein catabolic process via the multivesicular body sorting pathway
IBA
GO_REF:0000033
ACCEPT
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.
Reason: VPS37C/ESCRT-I supports ubiquitin-dependent endosomal cargo sorting into multivesicular bodies.
Supporting Evidence:
file:human/VPS37C/VPS37C-uniprot.txt
Required for the sorting of endocytic
file:human/VPS37C/VPS37C-uniprot.txt
ubiquitinated cargos into multivesicular bodies
PMID:15509564
required for the sorting of ubiquitinated transmembrane proteins into internal vesicles of multivesicular bodies
PMID:15509564
binds to another class E VPS factor, namely Hrs
PMID:18005716
plays essential roles in HIV budding and endosomal protein sorting
GO:0000813 ESCRT I complex
IBA
GO_REF:0000033
ACCEPT
Summary: ESCRT-I complex membership is a central VPS37C cellular-component annotation.
Reason: VPS37C is a VPS37-family ESCRT-I subunit that complexes with TSG101, VPS28, and fourth-subunit partners.
Supporting Evidence:
file:human/VPS37C/VPS37C-uniprot.txt
Component of the ESCRT-I complex
file:human/VPS37C/VPS37C-uniprot.txt
which consists of TSG101, VPS28, a VPS37
file:human/VPS37C/VPS37C-uniprot.txt
Interacts with TSG101, VPS28, MVB12A and MVB12B
PMID:15509564
VPS37C can form a ternary complex with Tsg101 and VPS28
PMID:15509564
Thus, this study identifies VPS37C as a functional component of mammalian ESCRT-I
PMID:18005716
All ESCRT-I complexes contain three common subunits (TSG101, VPS28, and VPS37)
PMID:22405001
complex with Vps23/TSG101, VPS28, and VPS37
GO:0006612 protein targeting to membrane
IBA
GO_REF:0000033
MODIFY
Summary: protein targeting to membrane is too broad for VPS37C ESCRT-I function.
Reason: The supported process is ESCRT-I-dependent endosomal cargo sorting into the MVB pathway, not generic protein targeting.
Supporting Evidence:
file:human/VPS37C/VPS37C-uniprot.txt
Required for the sorting of endocytic
file:human/VPS37C/VPS37C-uniprot.txt
ubiquitinated cargos into multivesicular bodies
PMID:15509564
required for the sorting of ubiquitinated transmembrane proteins into internal vesicles of multivesicular bodies
PMID:15509564
binds to another class E VPS factor, namely Hrs
PMID:18005716
plays essential roles in HIV budding and endosomal protein sorting
GO:0006623 protein targeting to vacuole
IBA
GO_REF:0000033
MODIFY
Summary: protein targeting to vacuole is too broad for VPS37C ESCRT-I function.
Reason: The supported process is ESCRT-I-dependent endosomal cargo sorting into the MVB pathway, not generic protein targeting.
Supporting Evidence:
file:human/VPS37C/VPS37C-uniprot.txt
Required for the sorting of endocytic
file:human/VPS37C/VPS37C-uniprot.txt
ubiquitinated cargos into multivesicular bodies
PMID:15509564
required for the sorting of ubiquitinated transmembrane proteins into internal vesicles of multivesicular bodies
PMID:15509564
binds to another class E VPS factor, namely Hrs
PMID:18005716
plays essential roles in HIV budding and endosomal protein sorting
GO:0000813 ESCRT I complex
IEA
GO_REF:0000117
ACCEPT
Summary: ESCRT-I complex membership is a central VPS37C cellular-component annotation.
Reason: VPS37C is a VPS37-family ESCRT-I subunit that complexes with TSG101, VPS28, and fourth-subunit partners.
Supporting Evidence:
file:human/VPS37C/VPS37C-uniprot.txt
Component of the ESCRT-I complex
file:human/VPS37C/VPS37C-uniprot.txt
which consists of TSG101, VPS28, a VPS37
file:human/VPS37C/VPS37C-uniprot.txt
Interacts with TSG101, VPS28, MVB12A and MVB12B
PMID:15509564
VPS37C can form a ternary complex with Tsg101 and VPS28
PMID:15509564
Thus, this study identifies VPS37C as a functional component of mammalian ESCRT-I
PMID:18005716
All ESCRT-I complexes contain three common subunits (TSG101, VPS28, and VPS37)
PMID:22405001
complex with Vps23/TSG101, VPS28, and VPS37
GO:0016236 macroautophagy
IEA
GO_REF:0000117
MARK AS OVER ANNOTATED
Summary: Macroautophagy is over-annotated for VPS37C.
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 replacements: ESCRT I complex
Supporting Evidence:
PMID:20588296
viral budding, cytokinesis and, probably, autophagy
PMID:20588296
direct neck closure reaction in autophagy
PMID:31519728
identify the ESCRT-I subunit VPS37A as a critical component
PMID:31519728
required for autophagosome completion
GO:0031902 late endosome membrane
IEA
GO_REF:0000044
ACCEPT
Summary: late endosome membrane localization is supported and relevant to VPS37C/ESCRT-I function.
Reason: VPS37C is a peripheral late-endosome/endosome-membrane ESCRT-I component recruited to aberrant endosomes in ESCRT perturbation assays.
Supporting Evidence:
file:human/VPS37C/VPS37C-uniprot.txt
Late endosome membrane
file:human/VPS37C/VPS37C-uniprot.txt
Probably associates with membranes
PMID:15509564
VPS37C is recruited to aberrant endosomes
GO:0036258 multivesicular body assembly
IEA
GO_REF:0000117
ACCEPT
Summary: multivesicular body assembly is supported as part of the core VPS37C/ESCRT-I endosomal cargo-sorting role.
Reason: VPS37C/ESCRT-I supports ubiquitin-dependent endosomal cargo sorting into multivesicular bodies.
Supporting Evidence:
file:human/VPS37C/VPS37C-uniprot.txt
Required for the sorting of endocytic
file:human/VPS37C/VPS37C-uniprot.txt
ubiquitinated cargos into multivesicular bodies
PMID:15509564
required for the sorting of ubiquitinated transmembrane proteins into internal vesicles of multivesicular bodies
PMID:15509564
binds to another class E VPS factor, namely Hrs
PMID:18005716
plays essential roles in HIV budding and endosomal protein sorting
GO:0039702 viral budding via host ESCRT complex
IEA
GO_REF:0000117
KEEP AS NON CORE
Summary: Viral budding via host ESCRT complex is supported as a secondary context but is not the core VPS37C proteostasis function.
Reason: VPS37C can support ESCRT-I-dependent viral budding, but the core cellular role is endosomal ESCRT-I cargo sorting.
Supporting Evidence:
PMID:15509564
VPS37C is recruited to the plasma membrane
PMID:15509564
direct fusion of VPS37C to HIV-1 Gag
PMID:15509564
inhibited by VPS37C depletion
PMID:18005716
plays essential roles in HIV budding and endosomal protein sorting
PMID:20588296
viral budding, cytokinesis and, probably, autophagy
GO:0048306 calcium-dependent protein binding
IEA
GO_REF:0000117
KEEP AS NON CORE
Summary: Calcium-dependent protein binding is supported but secondary.
Reason: VPS37C participates in an ALG-2/ALIX/ESCRT-I calcium-dependent ternary-complex context, but this is not the core VPS37C proteostasis function.
Supporting Evidence:
PMID:23924735
VPS37B and VPS37C appeared to interact with ALG-2
PMID:23924735
adaptor protein that bridges ALIX and ESCRT-I
GO:0005515 protein binding
IPI
PMID:17853893
Human ESCRT and ALIX proteins interact with proteins of the ...
MARK AS OVER ANNOTATED
Summary: Protein binding is too generic to represent VPS37C function.
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 replacements: ESCRT I complex
Supporting Evidence:
PMID:15509564
VPS37C can form a ternary complex with Tsg101 and VPS28
file:human/VPS37C/VPS37C-notes.md
Generic `protein binding` rows are over-annotated
GO:0005515 protein binding
IPI
PMID:25416956
A proteome-scale map of the human interactome network.
MARK AS OVER ANNOTATED
Summary: Protein binding is too generic to represent VPS37C function.
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 replacements: ESCRT I complex
Supporting Evidence:
PMID:15509564
VPS37C can form a ternary complex with Tsg101 and VPS28
file:human/VPS37C/VPS37C-notes.md
Generic `protein binding` rows are over-annotated
GO:0005515 protein binding
IPI
PMID:31515488
Extensive disruption of protein interactions by genetic vari...
MARK AS OVER ANNOTATED
Summary: Protein binding is too generic to represent VPS37C function.
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 replacements: ESCRT I complex
Supporting Evidence:
PMID:15509564
VPS37C can form a ternary complex with Tsg101 and VPS28
file:human/VPS37C/VPS37C-notes.md
Generic `protein binding` rows are over-annotated
GO:0005515 protein binding
IPI
PMID:32296183
A reference map of the human binary protein interactome.
MARK AS OVER ANNOTATED
Summary: Protein binding is too generic to represent VPS37C function.
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 replacements: ESCRT I complex
Supporting Evidence:
PMID:15509564
VPS37C can form a ternary complex with Tsg101 and VPS28
file:human/VPS37C/VPS37C-notes.md
Generic `protein binding` rows are over-annotated
GO:0005515 protein binding
IPI
PMID:35271311
OpenCell: Endogenous tagging for the cartography of human ce...
MARK AS OVER ANNOTATED
Summary: Protein binding is too generic to represent VPS37C function.
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 replacements: ESCRT I complex
Supporting Evidence:
PMID:15509564
VPS37C can form a ternary complex with Tsg101 and VPS28
file:human/VPS37C/VPS37C-notes.md
Generic `protein binding` rows are over-annotated
GO:0005654 nucleoplasm
IDA
GO_REF:0000052
KEEP AS NON CORE
Summary: Nucleoplasm localization is not part of the core VPS37C ESCRT-I function.
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.
Supporting Evidence:
file:human/VPS37C/VPS37C-notes.md
Extracellular exosome and nucleoplasm rows come from high-throughput localization/proteomics and should remain non-core
GO:0000813 ESCRT I complex
IPI
PMID:18005716
Identification of human MVB12 proteins as ESCRT-I subunits t...
ACCEPT
Summary: ESCRT-I complex membership is a central VPS37C cellular-component annotation.
Reason: VPS37C is a VPS37-family ESCRT-I subunit that complexes with TSG101, VPS28, and fourth-subunit partners.
Supporting Evidence:
file:human/VPS37C/VPS37C-uniprot.txt
Component of the ESCRT-I complex
file:human/VPS37C/VPS37C-uniprot.txt
which consists of TSG101, VPS28, a VPS37
file:human/VPS37C/VPS37C-uniprot.txt
Interacts with TSG101, VPS28, MVB12A and MVB12B
PMID:15509564
VPS37C can form a ternary complex with Tsg101 and VPS28
PMID:15509564
Thus, this study identifies VPS37C as a functional component of mammalian ESCRT-I
PMID:18005716
All ESCRT-I complexes contain three common subunits (TSG101, VPS28, and VPS37)
PMID:22405001
complex with Vps23/TSG101, VPS28, and VPS37
GO:0000813 ESCRT I complex
IPI
PMID:21757351
UBAP1 is a component of an endosome-specific ESCRT-I complex...
ACCEPT
Summary: ESCRT-I complex membership is correct for VPS37C, but PMID:21757351 is not the strongest VPS37C-specific support.
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.
Supporting Evidence:
file:human/VPS37C/VPS37C-uniprot.txt
Component of the ESCRT-I complex
file:human/VPS37C/VPS37C-uniprot.txt
which consists of TSG101, VPS28, a VPS37
file:human/VPS37C/VPS37C-uniprot.txt
Interacts with TSG101, VPS28, MVB12A and MVB12B
PMID:15509564
VPS37C can form a ternary complex with Tsg101 and VPS28
PMID:15509564
Thus, this study identifies VPS37C as a functional component of mammalian ESCRT-I
PMID:21757351
contains VPS37A but not VPS37C
GO:0010008 endosome membrane
NAS
PMID:32424346
A helical assembly of human ESCRT-I scaffolds reverse-topolo...
ACCEPT
Summary: endosome membrane is correct for VPS37C, but PMID:32424346 is indirect for this isoform.
Reason: Endosome-membrane localization is supported by VPS37C-specific evidence; PMID:32424346 supports general ESCRT-I mechanism using a VPS37B-containing headpiece.
Supporting Evidence:
file:human/VPS37C/VPS37C-uniprot.txt
Late endosome membrane
file:human/VPS37C/VPS37C-uniprot.txt
Probably associates with membranes
PMID:15509564
VPS37C is recruited to aberrant endosomes
PMID:32424346
comprising TSG101-VPS28-VPS37B-MVB12A
GO:0036258 multivesicular body assembly
NAS
PMID:32424346
A helical assembly of human ESCRT-I scaffolds reverse-topolo...
ACCEPT
Summary: multivesicular body assembly is supported as part of the core VPS37C/ESCRT-I endosomal cargo-sorting role.
Reason: VPS37C/ESCRT-I supports ubiquitin-dependent endosomal cargo sorting into multivesicular bodies.
Supporting Evidence:
file:human/VPS37C/VPS37C-uniprot.txt
Required for the sorting of endocytic
file:human/VPS37C/VPS37C-uniprot.txt
ubiquitinated cargos into multivesicular bodies
PMID:15509564
required for the sorting of ubiquitinated transmembrane proteins into internal vesicles of multivesicular bodies
PMID:15509564
binds to another class E VPS factor, namely Hrs
PMID:18005716
plays essential roles in HIV budding and endosomal protein sorting
GO:0043328 protein transport to vacuole involved in ubiquitin-dependent protein catabolic process via the multivesicular body sorting pathway
NAS
PMID:32424346
A helical assembly of human ESCRT-I scaffolds reverse-topolo...
ACCEPT
Summary: protein transport to vacuole involved in ubiquitin-dependent protein catabolic process via the multivesicular body sorting pathway is supported as part of the core VPS37C/ESCRT-I endosomal cargo-sorting role.
Reason: VPS37C/ESCRT-I supports ubiquitin-dependent endosomal cargo sorting into multivesicular bodies.
Supporting Evidence:
file:human/VPS37C/VPS37C-uniprot.txt
Required for the sorting of endocytic
file:human/VPS37C/VPS37C-uniprot.txt
ubiquitinated cargos into multivesicular bodies
PMID:15509564
required for the sorting of ubiquitinated transmembrane proteins into internal vesicles of multivesicular bodies
PMID:15509564
binds to another class E VPS factor, namely Hrs
PMID:18005716
plays essential roles in HIV budding and endosomal protein sorting
GO:0090148 membrane fission
NAS
PMID:32424346
A helical assembly of human ESCRT-I scaffolds reverse-topolo...
MARK AS OVER ANNOTATED
Summary: Membrane fission is a broad ESCRT-I mechanism annotation and is over-transferred for VPS37C as written.
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.
Supporting Evidence:
PMID:32424346
comprising TSG101-VPS28-VPS37B-MVB12A
PMID:32424346
ESCRT-I is not merely a bridging adaptor
PMID:15509564
functional component of mammalian ESCRT-I
GO:0016236 macroautophagy
TAS
PMID:20588296
Membrane budding and scission by the ESCRT machinery: it's a...
MARK AS OVER ANNOTATED
Summary: Macroautophagy is over-annotated for VPS37C.
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 replacements: ESCRT I complex
Supporting Evidence:
PMID:20588296
viral budding, cytokinesis and, probably, autophagy
PMID:20588296
direct neck closure reaction in autophagy
PMID:31519728
identify the ESCRT-I subunit VPS37A as a critical component
PMID:31519728
required for autophagosome completion
GO:0000813 ESCRT I complex
TAS
PMID:20588296
Membrane budding and scission by the ESCRT machinery: it's a...
ACCEPT
Summary: ESCRT-I complex membership is a central VPS37C cellular-component annotation.
Reason: VPS37C is a VPS37-family ESCRT-I subunit that complexes with TSG101, VPS28, and fourth-subunit partners.
Supporting Evidence:
file:human/VPS37C/VPS37C-uniprot.txt
Component of the ESCRT-I complex
file:human/VPS37C/VPS37C-uniprot.txt
which consists of TSG101, VPS28, a VPS37
file:human/VPS37C/VPS37C-uniprot.txt
Interacts with TSG101, VPS28, MVB12A and MVB12B
PMID:15509564
VPS37C can form a ternary complex with Tsg101 and VPS28
PMID:15509564
Thus, this study identifies VPS37C as a functional component of mammalian ESCRT-I
PMID:18005716
All ESCRT-I complexes contain three common subunits (TSG101, VPS28, and VPS37)
PMID:22405001
complex with Vps23/TSG101, VPS28, and VPS37
GO:0036258 multivesicular body assembly
TAS
PMID:20588296
Membrane budding and scission by the ESCRT machinery: it's a...
ACCEPT
Summary: multivesicular body assembly is supported as part of the core VPS37C/ESCRT-I endosomal cargo-sorting role.
Reason: VPS37C/ESCRT-I supports ubiquitin-dependent endosomal cargo sorting into multivesicular bodies.
Supporting Evidence:
file:human/VPS37C/VPS37C-uniprot.txt
Required for the sorting of endocytic
file:human/VPS37C/VPS37C-uniprot.txt
ubiquitinated cargos into multivesicular bodies
PMID:15509564
required for the sorting of ubiquitinated transmembrane proteins into internal vesicles of multivesicular bodies
PMID:15509564
binds to another class E VPS factor, namely Hrs
PMID:18005716
plays essential roles in HIV budding and endosomal protein sorting
GO:0039702 viral budding via host ESCRT complex
TAS
PMID:20588296
Membrane budding and scission by the ESCRT machinery: it's a...
KEEP AS NON CORE
Summary: Viral budding via host ESCRT complex is supported as a secondary context but is not the core VPS37C proteostasis function.
Reason: VPS37C can support ESCRT-I-dependent viral budding, but the core cellular role is endosomal ESCRT-I cargo sorting.
Supporting Evidence:
PMID:15509564
VPS37C is recruited to the plasma membrane
PMID:15509564
direct fusion of VPS37C to HIV-1 Gag
PMID:15509564
inhibited by VPS37C depletion
PMID:18005716
plays essential roles in HIV budding and endosomal protein sorting
PMID:20588296
viral budding, cytokinesis and, probably, autophagy
GO:0000813 ESCRT I complex
IDA
PMID:18005716
Identification of human MVB12 proteins as ESCRT-I subunits t...
ACCEPT
Summary: ESCRT-I complex membership is a central VPS37C cellular-component annotation.
Reason: VPS37C is a VPS37-family ESCRT-I subunit that complexes with TSG101, VPS28, and fourth-subunit partners.
Supporting Evidence:
file:human/VPS37C/VPS37C-uniprot.txt
Component of the ESCRT-I complex
file:human/VPS37C/VPS37C-uniprot.txt
which consists of TSG101, VPS28, a VPS37
file:human/VPS37C/VPS37C-uniprot.txt
Interacts with TSG101, VPS28, MVB12A and MVB12B
PMID:15509564
VPS37C can form a ternary complex with Tsg101 and VPS28
PMID:15509564
Thus, this study identifies VPS37C as a functional component of mammalian ESCRT-I
PMID:18005716
All ESCRT-I complexes contain three common subunits (TSG101, VPS28, and VPS37)
PMID:22405001
complex with Vps23/TSG101, VPS28, and VPS37
GO:0005515 protein binding
IPI
PMID:23924735
VPS37 isoforms differentially modulate the ternary complex f...
MARK AS OVER ANNOTATED
Summary: Protein binding is too generic to represent VPS37C function.
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.
Supporting Evidence:
PMID:23924735
VPS37B and VPS37C appeared to interact with ALG-2
PMID:23924735
adaptor protein that bridges ALIX and ESCRT-I
GO:0048306 calcium-dependent protein binding
IPI
PMID:23924735
VPS37 isoforms differentially modulate the ternary complex f...
KEEP AS NON CORE
Summary: Calcium-dependent protein binding is supported but secondary.
Reason: VPS37C participates in an ALG-2/ALIX/ESCRT-I calcium-dependent ternary-complex context, but this is not the core VPS37C proteostasis function.
Supporting Evidence:
PMID:23924735
VPS37B and VPS37C appeared to interact with ALG-2
PMID:23924735
adaptor protein that bridges ALIX and ESCRT-I
GO:0070062 extracellular exosome
HDA
PMID:23533145
In-depth proteomic analyses of exosomes isolated from expres...
KEEP AS NON CORE
Summary: Extracellular exosome is a high-throughput proteomics/localization context and not a core VPS37C annotation.
Reason: Exosome detection is not the central VPS37C ESCRT-I endosomal sorting function.
Supporting Evidence:
PMID:19056867
Large-scale proteomics and phosphoproteomics of urinary exosomes
PMID:23533145
In-depth proteomic analyses of exosomes
GO:0070062 extracellular exosome
HDA
PMID:19056867
Large-scale proteomics and phosphoproteomics of urinary exos...
KEEP AS NON CORE
Summary: Extracellular exosome is a high-throughput proteomics/localization context and not a core VPS37C annotation.
Reason: Exosome detection is not the central VPS37C ESCRT-I endosomal sorting function.
Supporting Evidence:
PMID:19056867
Large-scale proteomics and phosphoproteomics of urinary exosomes
PMID:23533145
In-depth proteomic analyses of exosomes
GO:0000813 ESCRT I complex
IDA
PMID:22405001
The UBAP1 subunit of ESCRT-I interacts with ubiquitin via a ...
ACCEPT
Summary: ESCRT-I complex membership is a central VPS37C cellular-component annotation.
Reason: VPS37C is a VPS37-family ESCRT-I subunit that complexes with TSG101, VPS28, and fourth-subunit partners.
Supporting Evidence:
file:human/VPS37C/VPS37C-uniprot.txt
Component of the ESCRT-I complex
file:human/VPS37C/VPS37C-uniprot.txt
which consists of TSG101, VPS28, a VPS37
file:human/VPS37C/VPS37C-uniprot.txt
Interacts with TSG101, VPS28, MVB12A and MVB12B
PMID:15509564
VPS37C can form a ternary complex with Tsg101 and VPS28
PMID:15509564
Thus, this study identifies VPS37C as a functional component of mammalian ESCRT-I
PMID:18005716
All ESCRT-I complexes contain three common subunits (TSG101, VPS28, and VPS37)
PMID:22405001
complex with Vps23/TSG101, VPS28, and VPS37
GO:0010008 endosome membrane
TAS
Reactome:R-HSA-184269
ACCEPT
Summary: endosome membrane localization is supported and relevant to VPS37C/ESCRT-I function.
Reason: VPS37C is a peripheral late-endosome/endosome-membrane ESCRT-I component recruited to aberrant endosomes in ESCRT perturbation assays.
Supporting Evidence:
file:human/VPS37C/VPS37C-uniprot.txt
Late endosome membrane
file:human/VPS37C/VPS37C-uniprot.txt
Probably associates with membranes
PMID:15509564
VPS37C is recruited to aberrant endosomes
GO:0010008 endosome membrane
TAS
Reactome:R-HSA-3149434
ACCEPT
Summary: endosome membrane localization is supported and relevant to VPS37C/ESCRT-I function.
Reason: VPS37C is a peripheral late-endosome/endosome-membrane ESCRT-I component recruited to aberrant endosomes in ESCRT perturbation assays.
Supporting Evidence:
file:human/VPS37C/VPS37C-uniprot.txt
Late endosome membrane
file:human/VPS37C/VPS37C-uniprot.txt
Probably associates with membranes
PMID:15509564
VPS37C is recruited to aberrant endosomes
GO:0010008 endosome membrane
TAS
Reactome:R-HSA-3159232
ACCEPT
Summary: endosome membrane localization is supported and relevant to VPS37C/ESCRT-I function.
Reason: VPS37C is a peripheral late-endosome/endosome-membrane ESCRT-I component recruited to aberrant endosomes in ESCRT perturbation assays.
Supporting Evidence:
file:human/VPS37C/VPS37C-uniprot.txt
Late endosome membrane
file:human/VPS37C/VPS37C-uniprot.txt
Probably associates with membranes
PMID:15509564
VPS37C is recruited to aberrant endosomes
GO:0010008 endosome membrane
TAS
Reactome:R-HSA-917696
ACCEPT
Summary: endosome membrane localization is supported and relevant to VPS37C/ESCRT-I function.
Reason: VPS37C is a peripheral late-endosome/endosome-membrane ESCRT-I component recruited to aberrant endosomes in ESCRT perturbation assays.
Supporting Evidence:
file:human/VPS37C/VPS37C-uniprot.txt
Late endosome membrane
file:human/VPS37C/VPS37C-uniprot.txt
Probably associates with membranes
PMID:15509564
VPS37C is recruited to aberrant endosomes
GO:0010008 endosome membrane
TAS
Reactome:R-HSA-917730
ACCEPT
Summary: endosome membrane localization is supported and relevant to VPS37C/ESCRT-I function.
Reason: VPS37C is a peripheral late-endosome/endosome-membrane ESCRT-I component recruited to aberrant endosomes in ESCRT perturbation assays.
Supporting Evidence:
file:human/VPS37C/VPS37C-uniprot.txt
Late endosome membrane
file:human/VPS37C/VPS37C-uniprot.txt
Probably associates with membranes
PMID:15509564
VPS37C is recruited to aberrant endosomes

Core Functions

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.

Supporting Evidence:
  • file:human/VPS37C/VPS37C-uniprot.txt
    Component of the ESCRT-I complex
  • file:human/VPS37C/VPS37C-uniprot.txt
    which consists of TSG101, VPS28, a VPS37
  • file:human/VPS37C/VPS37C-uniprot.txt
    Interacts with TSG101, VPS28, MVB12A and MVB12B
  • PMID:15509564
    VPS37C can form a ternary complex with Tsg101 and VPS28
  • PMID:15509564
    Thus, this study identifies VPS37C as a functional component of mammalian ESCRT-I
  • PMID:18005716
    All ESCRT-I complexes contain three common subunits (TSG101, VPS28, and VPS37)
  • PMID:22405001
    complex with Vps23/TSG101, VPS28, and VPS37
  • file:human/VPS37C/VPS37C-uniprot.txt
    Required for the sorting of endocytic
  • file:human/VPS37C/VPS37C-uniprot.txt
    ubiquitinated cargos into multivesicular bodies
  • PMID:15509564
    required for the sorting of ubiquitinated transmembrane proteins into internal vesicles of multivesicular bodies
  • PMID:15509564
    binds to another class E VPS factor, namely Hrs
  • PMID:18005716
    plays essential roles in HIV budding and endosomal protein sorting
  • file:human/VPS37C/VPS37C-uniprot.txt
    Late endosome membrane
  • file:human/VPS37C/VPS37C-uniprot.txt
    Probably associates with membranes
  • PMID:15509564
    VPS37C is recruited to aberrant endosomes

References

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Suggested Questions for Experts

Q: Should VPS37C macroautophagy annotations be retired or kept non-core given that the direct phagophore-closure evidence is VPS37A-specific?

Suggested experts: GO autophagy editors, GO ESCRT curators

Q: Should generic VPS37C protein-binding annotations be replaced by ESCRT-I complex membership, calcium-dependent ALG-2 interaction context, and specific endosomal sorting terms?

Suggested experts: GO molecular function editors, UniProt curators

Suggested Experiments

Experiment: 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.

Hypothesis: VPS37A, but not necessarily VPS37C, is the VPS37 paralog specialized for phagophore closure.

Type: VPS37 paralog phagophore closure comparison

Experiment: Use VPS37C-specific knockout-rescue with quantitative cargo degradation and HIV-1 Gag recruitment/release readouts, controlling for VPS37A and VPS37B compensation.

Hypothesis: VPS37C contributes to a subset of ESCRT-I cargo-sorting or viral-budding contexts distinct from the UBAP1/VPS37A endosome-specific complex.

Type: VPS37C-specific MVB sorting assay

πŸ“š Additional Documentation

Notes

(VPS37C-notes.md)

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Pn Notes

(VPS37C-pn-notes.md)

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πŸ“„ View Raw YAML

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