VPS37D is a VPS37-family ESCRT-I subunit in TSG101-VPS28-VPS37-MVB12/UBAP-family complexes. The best-supported cellular function is ESCRT-I-dependent endosomal sorting of ubiquitinated cargo into multivesicular bodies, with late-endosome/endosome-membrane localization. Current local evidence does not support transferring VPS37A-specific phagophore-closure or VPS37B/VPS28 structural membrane-fission assays to VPS37D as core annotations.
| 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 VPS37D/ESCRT-I endosomal cargo-sorting role. Reason: VPS37D is annotated as an ESCRT-I subunit required for ubiquitin-dependent endosomal cargo sorting into multivesicular bodies. Supporting Evidence: file:human/VPS37D/VPS37D-uniprot.txt Required for the sorting of endocytic file:human/VPS37D/VPS37D-uniprot.txt ubiquitinated cargos into multivesicular bodies PMID:15218037 sorting ubiquitylated protein cargoes into multivesicular bodies 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 the central VPS37D cellular-component annotation. Reason: VPS37D is a VPS37-family ESCRT-I subunit in TSG101-VPS28-VPS37-MVB12/UBAP variant complexes, although direct VPS37D-specific functional evidence is limited. The falcon deep research independently corroborates VPS37D as a bona fide core ESCRT-I subunit while cautioning that it is the least functionally characterized of the four human paralogs. Supporting Evidence: file:human/VPS37D/VPS37D-uniprot.txt Component of the ESCRT-I complex file:human/VPS37D/VPS37D-uniprot.txt which consists of TSG101, VPS28, a VPS37 file:human/VPS37D/VPS37D-uniprot.txt Interacts with TSG101 and MVB12A PMID:15218037 proteins (VPS37A-D) that share weak but significant sequence similarity 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/VPS37D/VPS37D-deep-research-falcon.md confirmed bona fide **human ESCRT-I core subunit**; included among mammalian VPS37A-D paralogs file:human/VPS37D/VPS37D-deep-research-falcon.md Least functionally characterized of the four human paralogs in primary mechanistic literature |
| GO:0006612 protein targeting to membrane | IBA GO_REF:0000033 | MODIFY | Summary: protein targeting to membrane is too broad for VPS37D 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/VPS37D/VPS37D-uniprot.txt Required for the sorting of endocytic file:human/VPS37D/VPS37D-uniprot.txt ubiquitinated cargos into multivesicular bodies PMID:15218037 sorting ubiquitylated protein cargoes into multivesicular bodies 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 VPS37D 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/VPS37D/VPS37D-uniprot.txt Required for the sorting of endocytic file:human/VPS37D/VPS37D-uniprot.txt ubiquitinated cargos into multivesicular bodies PMID:15218037 sorting ubiquitylated protein cargoes into multivesicular bodies 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 the central VPS37D cellular-component annotation. Reason: VPS37D is a VPS37-family ESCRT-I subunit in TSG101-VPS28-VPS37-MVB12/UBAP variant complexes, although direct VPS37D-specific functional evidence is limited. Supporting Evidence: file:human/VPS37D/VPS37D-uniprot.txt Component of the ESCRT-I complex file:human/VPS37D/VPS37D-uniprot.txt which consists of TSG101, VPS28, a VPS37 file:human/VPS37D/VPS37D-uniprot.txt Interacts with TSG101 and MVB12A PMID:15218037 proteins (VPS37A-D) that share weak but significant sequence similarity 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/VPS37D/VPS37D-deep-research-falcon.md confirmed bona fide **human ESCRT-I core subunit**; included among mammalian VPS37A-D paralogs file:human/VPS37D/VPS37D-deep-research-falcon.md Least functionally characterized of the four human paralogs in primary mechanistic literature |
| GO:0031902 late endosome membrane | IEA GO_REF:0000044 | ACCEPT | Summary: late endosome membrane localization is supported and relevant to VPS37D/ESCRT-I function. Reason: VPS37D is a peripheral late-endosome/endosome-membrane ESCRT-I component in local and Reactome context. Supporting Evidence: file:human/VPS37D/VPS37D-uniprot.txt Late endosome membrane file:human/VPS37D/VPS37D-uniprot.txt Peripheral membrane protein |
| 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 VPS37D function. Reason: The informative annotations are ESCRT-I complex membership and endosomal MVB sorting, not generic protein binding from a broad interaction screen. The falcon deep research notes that, unlike VPS37B/C, VPS37D does not have the selective SH3YL1 or CDIP1 interactions reported for those paralogs, so no specific informative interaction partner can be assigned to VPS37D from the literature to replace this generic term. Proposed replacements: ESCRT I complex Supporting Evidence: file:human/VPS37D/VPS37D-notes.md The generic `protein binding` row comes from a broad interactome annotation file:human/VPS37D/VPS37D-deep-research-falcon.md does **not** show the same highlighted SH3YL1 or CDIP1 preference reported for VPS37B/C |
| GO:0000813 ESCRT I complex | IPI PMID:18005716 Identification of human MVB12 proteins as ESCRT-I subunits t... | ACCEPT | Summary: ESCRT-I complex membership is the central VPS37D cellular-component annotation. Reason: VPS37D is a VPS37-family ESCRT-I subunit in TSG101-VPS28-VPS37-MVB12/UBAP variant complexes, although direct VPS37D-specific functional evidence is limited. Supporting Evidence: file:human/VPS37D/VPS37D-uniprot.txt Component of the ESCRT-I complex file:human/VPS37D/VPS37D-uniprot.txt which consists of TSG101, VPS28, a VPS37 file:human/VPS37D/VPS37D-uniprot.txt Interacts with TSG101 and MVB12A PMID:15218037 proteins (VPS37A-D) that share weak but significant sequence similarity 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/VPS37D/VPS37D-deep-research-falcon.md confirmed bona fide **human ESCRT-I core subunit**; included among mammalian VPS37A-D paralogs file:human/VPS37D/VPS37D-deep-research-falcon.md Least functionally characterized of the four human paralogs in primary mechanistic literature |
| 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 VPS37D, but PMID:21757351 is indirect for this isoform. Reason: The term is correct from UniProt and shared ESCRT-I evidence; PMID:21757351 mainly defines an endosome-specific UBAP1/VPS37A complex and should not be treated as direct VPS37D functional support. Supporting Evidence: file:human/VPS37D/VPS37D-uniprot.txt Component of the ESCRT-I complex file:human/VPS37D/VPS37D-uniprot.txt which consists of TSG101, VPS28, a VPS37 file:human/VPS37D/VPS37D-uniprot.txt Interacts with TSG101 and MVB12A PMID:15218037 proteins (VPS37A-D) that share weak but significant sequence similarity PMID:18005716 All ESCRT-I complexes contain three common subunits (TSG101, VPS28, and VPS37) 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 VPS37D, but PMID:32424346 is indirect for this isoform. Reason: Endosome-membrane localization is supported by VPS37D context; PMID:32424346 supports general ESCRT-I mechanism using a VPS37B-containing headpiece. Supporting Evidence: file:human/VPS37D/VPS37D-uniprot.txt Late endosome membrane file:human/VPS37D/VPS37D-uniprot.txt Peripheral membrane protein 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 biologically consistent with VPS37D ESCRT-I function, but PMID:32424346 is indirect for this isoform. Reason: The term is supported by VPS37D ESCRT-I/MVB context; PMID:32424346 supports general ESCRT-I mechanism using a VPS37B-containing headpiece. Supporting Evidence: file:human/VPS37D/VPS37D-uniprot.txt Required for the sorting of endocytic file:human/VPS37D/VPS37D-uniprot.txt ubiquitinated cargos into multivesicular bodies PMID:15218037 sorting ubiquitylated protein cargoes into multivesicular bodies PMID:18005716 plays essential roles in HIV budding and endosomal protein sorting PMID:32424346 comprising TSG101-VPS28-VPS37B-MVB12A |
| 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 biologically consistent with VPS37D ESCRT-I function, but PMID:32424346 is indirect for this isoform. Reason: The term is supported by VPS37D ESCRT-I/MVB context; PMID:32424346 supports general ESCRT-I mechanism using a VPS37B-containing headpiece. Supporting Evidence: file:human/VPS37D/VPS37D-uniprot.txt Required for the sorting of endocytic file:human/VPS37D/VPS37D-uniprot.txt ubiquitinated cargos into multivesicular bodies PMID:15218037 sorting ubiquitylated protein cargoes into multivesicular bodies PMID:18005716 plays essential roles in HIV budding and endosomal protein sorting PMID:32424346 comprising TSG101-VPS28-VPS37B-MVB12A |
| 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 VPS37D as written. Reason: The cited structural/autophagy work directly tested a VPS37B-containing headpiece and VPS28 interface mutants, not VPS37D; the safer VPS37D 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 |
| 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 VPS37D. Reason: The accessible ESCRT autophagy evidence is broad or VPS37A-specific; there is not enough direct evidence to make VPS37D a phagophore-closure/autophagosome assembly factor. The autophagy-specialized ESCRT-I module is built on VPS37A's N-terminal ubiquitin E2 variant-like (UEVL) region; the falcon deep research notes that no equivalent VPS37A-like autophagy UEVL specialization has been established for VPS37D, reinforcing that macroautophagy should not be a VPS37D core annotation. 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 file:human/VPS37D/VPS37D-deep-research-falcon.md no VPS37A-like autophagy UEVL specialization has been established in the cited studies |
| GO:0000813 ESCRT I complex | TAS PMID:20588296 Membrane budding and scission by the ESCRT machinery: it's a... | ACCEPT | Summary: ESCRT-I complex membership is the central VPS37D cellular-component annotation. Reason: VPS37D is a VPS37-family ESCRT-I subunit in TSG101-VPS28-VPS37-MVB12/UBAP variant complexes, although direct VPS37D-specific functional evidence is limited. Supporting Evidence: file:human/VPS37D/VPS37D-uniprot.txt Component of the ESCRT-I complex file:human/VPS37D/VPS37D-uniprot.txt which consists of TSG101, VPS28, a VPS37 file:human/VPS37D/VPS37D-uniprot.txt Interacts with TSG101 and MVB12A PMID:15218037 proteins (VPS37A-D) that share weak but significant sequence similarity 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/VPS37D/VPS37D-deep-research-falcon.md confirmed bona fide **human ESCRT-I core subunit**; included among mammalian VPS37A-D paralogs file:human/VPS37D/VPS37D-deep-research-falcon.md Least functionally characterized of the four human paralogs in primary mechanistic literature |
| 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 VPS37D/ESCRT-I endosomal cargo-sorting role. Reason: VPS37D is annotated as an ESCRT-I subunit required for ubiquitin-dependent endosomal cargo sorting into multivesicular bodies. Supporting Evidence: file:human/VPS37D/VPS37D-uniprot.txt Required for the sorting of endocytic file:human/VPS37D/VPS37D-uniprot.txt ubiquitinated cargos into multivesicular bodies PMID:15218037 sorting ubiquitylated protein cargoes into multivesicular bodies 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 a supported ESCRT context but is not the core VPS37D proteostasis function. Reason: Viral budding uses ESCRT-I machinery, but VPS37D-specific direct viral-budding evidence is limited and the core cellular role remains endosomal ESCRT-I cargo sorting. Supporting Evidence: 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 the central VPS37D cellular-component annotation. Reason: VPS37D is a VPS37-family ESCRT-I subunit in TSG101-VPS28-VPS37-MVB12/UBAP variant complexes, although direct VPS37D-specific functional evidence is limited. Supporting Evidence: file:human/VPS37D/VPS37D-uniprot.txt Component of the ESCRT-I complex file:human/VPS37D/VPS37D-uniprot.txt which consists of TSG101, VPS28, a VPS37 file:human/VPS37D/VPS37D-uniprot.txt Interacts with TSG101 and MVB12A PMID:15218037 proteins (VPS37A-D) that share weak but significant sequence similarity 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/VPS37D/VPS37D-deep-research-falcon.md confirmed bona fide **human ESCRT-I core subunit**; included among mammalian VPS37A-D paralogs file:human/VPS37D/VPS37D-deep-research-falcon.md Least functionally characterized of the four human paralogs in primary mechanistic literature |
| 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 VPS37D annotation. Reason: Exosome detection is not the central VPS37D 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 VPS37D annotation. Reason: Exosome detection is not the central VPS37D 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 the central VPS37D cellular-component annotation. Reason: VPS37D is a VPS37-family ESCRT-I subunit in TSG101-VPS28-VPS37-MVB12/UBAP variant complexes, although direct VPS37D-specific functional evidence is limited. Supporting Evidence: file:human/VPS37D/VPS37D-uniprot.txt Component of the ESCRT-I complex file:human/VPS37D/VPS37D-uniprot.txt which consists of TSG101, VPS28, a VPS37 file:human/VPS37D/VPS37D-uniprot.txt Interacts with TSG101 and MVB12A PMID:15218037 proteins (VPS37A-D) that share weak but significant sequence similarity 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/VPS37D/VPS37D-deep-research-falcon.md confirmed bona fide **human ESCRT-I core subunit**; included among mammalian VPS37A-D paralogs file:human/VPS37D/VPS37D-deep-research-falcon.md Least functionally characterized of the four human paralogs in primary mechanistic literature |
| GO:0010008 endosome membrane | TAS Reactome:R-HSA-184269 | ACCEPT | Summary: endosome membrane localization is supported and relevant to VPS37D/ESCRT-I function. Reason: VPS37D is a peripheral late-endosome/endosome-membrane ESCRT-I component in local and Reactome context. Supporting Evidence: file:human/VPS37D/VPS37D-uniprot.txt Late endosome membrane file:human/VPS37D/VPS37D-uniprot.txt Peripheral membrane protein |
| GO:0010008 endosome membrane | TAS Reactome:R-HSA-3149434 | ACCEPT | Summary: endosome membrane localization is supported and relevant to VPS37D/ESCRT-I function. Reason: VPS37D is a peripheral late-endosome/endosome-membrane ESCRT-I component in local and Reactome context. Supporting Evidence: file:human/VPS37D/VPS37D-uniprot.txt Late endosome membrane file:human/VPS37D/VPS37D-uniprot.txt Peripheral membrane protein |
| GO:0010008 endosome membrane | TAS Reactome:R-HSA-3159232 | ACCEPT | Summary: endosome membrane localization is supported and relevant to VPS37D/ESCRT-I function. Reason: VPS37D is a peripheral late-endosome/endosome-membrane ESCRT-I component in local and Reactome context. Supporting Evidence: file:human/VPS37D/VPS37D-uniprot.txt Late endosome membrane file:human/VPS37D/VPS37D-uniprot.txt Peripheral membrane protein |
| GO:0010008 endosome membrane | TAS Reactome:R-HSA-917696 | ACCEPT | Summary: endosome membrane localization is supported and relevant to VPS37D/ESCRT-I function. Reason: VPS37D is a peripheral late-endosome/endosome-membrane ESCRT-I component in local and Reactome context. Supporting Evidence: file:human/VPS37D/VPS37D-uniprot.txt Late endosome membrane file:human/VPS37D/VPS37D-uniprot.txt Peripheral membrane protein |
| GO:0010008 endosome membrane | TAS Reactome:R-HSA-917730 | ACCEPT | Summary: endosome membrane localization is supported and relevant to VPS37D/ESCRT-I function. Reason: VPS37D is a peripheral late-endosome/endosome-membrane ESCRT-I component in local and Reactome context. Supporting Evidence: file:human/VPS37D/VPS37D-uniprot.txt Late endosome membrane file:human/VPS37D/VPS37D-uniprot.txt Peripheral membrane protein |
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Download this section (compressed HTML)Q: Should VPS37D 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 VPS37D protein-binding annotations be replaced by ESCRT-I complex membership and specific endosomal sorting terms?
Suggested experts: GO molecular function editors, UniProt curators
Experiment: Compare VPS37A, VPS37B, VPS37C, and VPS37D 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 VPS37D, is the VPS37 paralog specialized for phagophore closure.
Type: VPS37 paralog phagophore closure comparison
Experiment: Use VPS37D-specific knockout-rescue with quantitative cargo degradation and ESCRT recruitment readouts, controlling for VPS37A/B/C compensation.
Hypothesis: VPS37D participates in a subset of ESCRT-I cargo-sorting contexts but lacks direct evidence for autophagosome closure.
Type: VPS37D-specific ESCRT-I cargo-sorting assay
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