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. Proposed replacements: ubiquitin-dependent protein catabolic process via the multivesicular body sorting pathway multivesicular body assembly 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. Proposed replacements: ubiquitin-dependent protein catabolic process via the multivesicular body sorting pathway multivesicular body assembly 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. Proposed replacements: ESCRT I complex multivesicular body assembly 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. Proposed replacements: calcium-dependent protein binding 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.

Directly Involved In:

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

Cellular Locations:

endosome membrane late endosome membrane

In Complex:

ESCRT I complex

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

GO_REF:0000033

Annotation inferences using phylogenetic trees

GO_REF:0000044

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

GO_REF:0000052

Gene Ontology annotation based on curation of immunofluorescence data

GO_REF:0000117

Electronic Gene Ontology annotations created by ARBA machine learning models

PMID:17853893

Human ESCRT and ALIX proteins interact with proteins of the midbody and function in cytokinesis.

PMID:18005716

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

PMID:19056867

Large-scale proteomics and phosphoproteomics of urinary exosomes.

PMID:20588296

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

PMID:21757351

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

PMID:22405001

The UBAP1 subunit of ESCRT-I interacts with ubiquitin via a SOUBA domain.

PMID:23533145

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

PMID:23924735

VPS37 isoforms differentially modulate the ternary complex formation of ALIX, ALG-2, and ESCRT-I.

PMID:25416956

A proteome-scale map of the human interactome network.

PMID:31515488

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

PMID:32296183

A reference map of the human binary protein interactome.

PMID:32424346

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

PMID:35271311

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

Reactome:R-HSA-184269

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

Reactome:R-HSA-3149434

Transport of GAG to the Plasma Membrane

Reactome:R-HSA-3159232

Recruitment Of HIV Virion Budding Machinery

Reactome:R-HSA-917696

Cargo Sequestration

Reactome:R-HSA-917730

Cargo Recognition And Sorting

PMID:15509564

Identification of human VPS37C, a component of endosomal sorting complex required for transport-I important for viral budding.

PMID:31519728

VPS37A directs ESCRT recruitment for phagophore closure.

file:human/VPS37C/VPS37C-uniprot.txt

UniProtKB record for human VPS37C

file:human/VPS37C/VPS37C-notes.md

VPS37C review notes

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

📚 Additional Documentation

Notes

(VPS37C-notes.md)

VPS37C review notes

Scope

VPS37C is reviewed in the PN ESCRT-I branch. PN entries without PMIDs were used as context only. The direct phagophore-closure evidence in this ESCRT-I neighborhood is VPS37A-specific; for VPS37C the supported core is ESCRT-I membership, endosomal MVB cargo sorting, late-endosome/endosome-membrane localization, and secondary ESCRT-I viral budding context.

Evidence synthesis

VPS37C is a VPS37-family ESCRT-I subunit. UniProt describes it as a "Component of the ESCRT-I complex" and says it is "Required for the sorting of endocytic ubiquitinated cargos into multivesicular bodies" [file:human/VPS37C/VPS37C-uniprot.txt, "Component of the ESCRT-I complex"; file:human/VPS37C/VPS37C-uniprot.txt, "Required for the sorting of endocytic"]. UniProt also states that human ESCRT-I "consists of TSG101, VPS28, a VPS37 protein" and that VPS37C interacts with TSG101, VPS28, MVB12A, MVB12B, HGS, STAM2, and CEP55 [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"; file:human/VPS37C/VPS37C-uniprot.txt, "Interacts with HGS and STAM2"]. These support ESCRT-I complex and endosomal MVB sorting annotations.

The main VPS37C paper identifies it as a functional mammalian ESCRT-I component. Its abstract reports that VPS37C is a Tsg101-binding protein, that "VPS37C can form a ternary complex with Tsg101 and VPS28", that it binds Hrs, and that it is recruited to aberrant endosomes induced by Tsg101, Hrs, or dominant-negative VPS4 [PMID:15509564, "VPS37C can form a ternary complex with Tsg101 and VPS28"; PMID:15509564, "binds to another class E VPS factor, namely Hrs"; PMID:15509564, "VPS37C is recruited to aberrant endosomes"]. The same paper shows a direct viral budding context: VPS37C is recruited to the plasma membrane with HIV-1 Gag, Gag-VPS37C fusion bypasses the PTAP requirement, and engineered ESCRT-I-dependent virus budding is inhibited by VPS37C depletion [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"]. Viral budding should be kept as a supported non-core context for this proteostasis review.

Human ESCRT-I composition papers support the shared complex architecture, but some should not be over-read as VPS37C-specific MVB evidence. PMID:18005716 says human ESCRT-I plays roles in HIV budding and endosomal sorting and that all ESCRT-I complexes contain TSG101, VPS28, and VPS37 [PMID:18005716, "plays essential roles in HIV budding and endosomal protein sorting"; PMID:18005716, "TSG101, VPS28, and VPS37"]. By contrast, the UBAP1 endosome-specific ESCRT-I paper says the UBAP1 complex "also contains VPS37A but not VPS37C" [PMID:21757351, "contains VPS37A but not VPS37C"]. Therefore PMID:21757351 is not used as direct support for VPS37C's core endosome-specific UBAP1 pathway, although the ESCRT-I complex term itself is supported by other references.

Structural ESCRT-I evidence supports the general mechanism but is not VPS37C-specific. PMID:32424346 determined the structure of a human ESCRT-I headpiece "comprising TSG101-VPS28-VPS37B-MVB12A" and found that ESCRT-I forms helical filaments with a scaffolding/mechanical role in reverse-topology scission [PMID:32424346, "comprising TSG101-VPS28-VPS37B-MVB12A"; PMID:32424346, "ESCRT-I is not merely a bridging adaptor"]. This supports the general ESCRT-I mechanism, but for VPS37C it should not be treated as direct evidence for autophagosome closure or a VPS37C-specific membrane-fission assay.

The macroautophagy rows should be treated cautiously. PMID:20588296 says ESCRT-III-mediated neck cleavage is crucial for MVBs, viral budding, cytokinesis, and "probably, autophagy", and explicitly notes that whether ESCRTs directly close autophagic necks remained unresolved [PMID:20588296, "viral budding, cytokinesis and, probably, autophagy"; PMID:20588296, "direct neck closure reaction in autophagy"]. The direct mammalian phagophore-closure paper identifies VPS37A, not VPS37C, as the VPS37-family ESCRT-I subunit needed for phagophore closure [PMID:31519728, "identify the ESCRT-I subunit VPS37A as a critical component"; PMID:31519728, "required for autophagosome completion"]. This argues against transferring an autophagosome assembly or macroautophagy core annotation to VPS37C without additional gene-specific evidence.

VPS37C has a secondary calcium-dependent ALIX/ALG-2 interaction context. PMID:23924735 reports that VPS37B and VPS37C interact with ALG-2 more strongly than TSG101 and that ALG-2 bridges ALIX and ESCRT-I [PMID:23924735, "VPS37B and VPS37C appeared to interact with ALG-2"; PMID:23924735, "adaptor protein that bridges ALIX and ESCRT-I"]. This supports keeping calcium-dependent protein binding as non-core rather than using generic protein binding as a molecular function.

Generic protein binding rows are over-annotated. The meaningful curation targets are ESCRT-I complex membership, MVB/endosomal sorting, late-endosome/endosome-membrane localization, and supported secondary ESCRT-I interaction contexts. Extracellular exosome and nucleoplasm rows come from high-throughput localization/proteomics and should remain non-core.

Falcon

Falcon deep research was started for VPS37C on 2026-06-02 but timed out after 600 seconds and did not produce a usable VPS37C-deep-research-falcon.md report. The review therefore relies on the local UniProt, GOA, cached-publication, Reactome, and PN-context evidence summarized above.

Pn Notes

(VPS37C-pn-notes.md)

VPS37C PN Consistency Notes

Generated: 2026-06-18
Project: PROTEOSTASIS
Scope: PN consistency rereview against local AIGR review and available deep-research artifacts
UniProt: A5D8V6
AIGR review status: COMPLETE
Review batch: proteostasis-pr-1217 (PR 1217)
Batch change status: added

Source Files Checked

AIGR review YAML: present - genes/human/VPS37C/VPS37C-ai-review.yaml
AIGR review HTML: present - genes/human/VPS37C/VPS37C-ai-review.html
Gene notes: present - genes/human/VPS37C/VPS37C-notes.md
GOA TSV: present - genes/human/VPS37C/VPS37C-goa.tsv
UniProt record: present - genes/human/VPS37C/VPS37C-uniprot.txt
PN dossier: projects/PROTEOSTASIS/reports/phase1_dossiers/VPS37C.md
PN consistency section: projects/PROTEOSTASIS/reports/phase1_dossiers/_sections/VPS37C.md
PN projection report: projects/PROTEOSTASIS/reports/pn_projection/pn_projected_gene_go_summary.tsv
PN mapping audit: projects/PROTEOSTASIS/reports/pn_mapping_audit/current_mapping_scrutiny.tsv

Deep Research Files

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

AIGR Review Snapshot

Description: 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/core annotation action counts: ACCEPT: 19; KEEP_AS_NON_CORE: 7; MARK_AS_OVER_ANNOTATED: 9; MODIFY: 2

PN Consistency Summary

Consistency: PARTIAL CONTRADICTION (same axis as VPS37B). ESCRT-I membership fully consistent: review ACCEPTs GO:0000813, with gene-specific support (ternary complex with TSG101/VPS28, PMID:15509564) and MVB sorting. Autophagy diverges: review MARK_AS_OVER_ANNOTATED both GO:0016236 macroautophagy rows and even MARK_AS_OVER_ANNOTATED a GO:0090148 membrane-fission row (noting the structural paper tested a VPS37B headpiece, not VPS37C), declining GO:0000045. PN still projects GO:0000045 to VPS37C.
PN story / NEW pressure: Over-reaches for autophagy. PN's group GO:0000045 asserts autophagosome assembly the review finds unsupported for VPS37C (phagophore closure is VPS37A-specific; PMID:21757351 explicitly notes UBAP1 ESCRT-I "contains VPS37A but not VPS37C"). ESCRT-I already captured. No NEW term beyond GO:0000813.
Evidence alignment: Partial. PN cites only PMID:32424346, which the review uses for general ESCRT-I mechanism but explicitly flags as not VPS37C-specific (VPS37B headpiece). Review adds VPS37C-specific PMID:15509564 and ALG-2 context PMID:23924735, absent from PN. PN omits the UBAP1 caveat (PMID:21757351) the review relies on.
Verdict: Consistent on ESCRT-I; GO:0000045 projection over-reaches. Recommended edits: none to YAML (review correctly omits GO:0000045); flag PN sealing-group→GO:0000045 as non-propagating to VPS37C.

Full Consistency Review

UniProt: A5D8V6 · batch: proteostasis-pr-1217 · review status: COMPLETE
PN placement: 1 row, ALP — Autophagosome closure maturation and lysosome fusion → Sealing of autophagophore membrane → ESCRT-I complex component. PN-node mapping: leaf=mapped→GO:0000813; sealing group=mapped→GO:0000045; class=context_only (GO:0016236). Projected: GO:0000045 (more_specific_than_existing_goa), GO:0000813 (already_in_goa_exact).
Consistency: PARTIAL CONTRADICTION (same axis as VPS37B). ESCRT-I membership fully consistent: review ACCEPTs GO:0000813, with gene-specific support (ternary complex with TSG101/VPS28, PMID:15509564) and MVB sorting. Autophagy diverges: review MARK_AS_OVER_ANNOTATED both GO:0016236 macroautophagy rows and even MARK_AS_OVER_ANNOTATED a GO:0090148 membrane-fission row (noting the structural paper tested a VPS37B headpiece, not VPS37C), declining GO:0000045. PN still projects GO:0000045 to VPS37C.
PN story / NEW pressure: Over-reaches for autophagy. PN's group GO:0000045 asserts autophagosome assembly the review finds unsupported for VPS37C (phagophore closure is VPS37A-specific; PMID:21757351 explicitly notes UBAP1 ESCRT-I "contains VPS37A but not VPS37C"). ESCRT-I already captured. No NEW term beyond GO:0000813.
Mapping strategy: Flag. Leaf→GO:0000813 correct (already in GOA). Group→GO:0000045 over-reaches for VPS37C — same shared-node over-reach pattern as TOMM20/HSPA8/RAB7A; GO:0000045 should not propagate to VPS37C without gene-specific evidence.
Evidence alignment: Partial. PN cites only PMID:32424346, which the review uses for general ESCRT-I mechanism but explicitly flags as not VPS37C-specific (VPS37B headpiece). Review adds VPS37C-specific PMID:15509564 and ALG-2 context PMID:23924735, absent from PN. PN omits the UBAP1 caveat (PMID:21757351) the review relies on.
Verdict: Consistent on ESCRT-I; GO:0000045 projection over-reaches. Recommended edits: none to YAML (review correctly omits GO:0000045); flag PN sealing-group→GO:0000045 as non-propagating to VPS37C.

PN Dossier Context

review_batch: proteostasis-pr-1217
review_yaml: genes/human/VPS37C/VPS37C-ai-review.yaml
PN workbook rows: 1

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

UniProt: A5D8V6
In branches: ALP
Notes: Component of the ESCRT-I complex, involved in autophagosome closure
PN references (titles):
- A helical assembly of human ESCRT-I scaffolds reverse-topology membrane scission | Nature Structural & Molecular Biology
PN-node mapping records (path + ancestors):
- [type] Autophagy-Lysosome Pathway|Autophagosome closure maturation and lysosome fusion|Sealing of autophagophore membrane|ESCRT-I complex component
  status=mapped scope=ok_for_propagation_to_go GO=[GO:0000813 ESCRT I complex]
  rationale: This leaf is restricted to ESCRT-I components used in autophagophore sealing. The shared GO assertion is ESCRT I complex membership.
- [group] Autophagy-Lysosome Pathway|Autophagosome closure maturation and lysosome fusion|Sealing of autophagophore membrane
  status=mapped scope=ok_for_propagation_to_go GO=[GO:0000045 autophagosome assembly]
  rationale: This group captures autophagophore closure/sealing, a late step in autophagosome assembly. Autophagosome assembly is the safer process target than autophagosome-lysosome fusion.
- [class] Autophagy-Lysosome Pathway|Autophagosome closure maturation and lysosome fusion
  status=context_only scope=too_broad_to_propagate GO=[GO:0016236 macroautophagy]
  rationale: This class is a late macroautophagy context, but the subtree mixes docking, fusion, localization, membrane-composition, and unknown late-stage roles. The class-level relation is useful for display while propagation is restricted to narrower mechanism nodes.
- [branch] Autophagy-Lysosome Pathway
  status=no_mapping scope= GO=[]
  rationale: Reviewed as the top-level PN branch. It is a project taxonomy umbrella rather than a direct GO assertion; all propagation must come from manually curated child nodes.

Projected GO annotations (2)

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

Note

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

📄 View Raw YAML

id: 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.

VPS37C

Gene Description

Existing Annotations Review

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.

References

Suggested Questions for Experts

Suggested Experiments

📚 Additional Documentation

Notes

VPS37C review notes

Scope

Evidence synthesis

Falcon

Pn Notes

VPS37C PN Consistency Notes

Source Files Checked

Deep Research Files

AIGR Review Snapshot

PN Consistency Summary

Full Consistency Review

PN Dossier Context

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

Projected GO annotations (2)

Note

📄 View Raw YAML