UVRAG is a regulatory/adaptor subunit of the UVRAG-containing class III PI3K complex II (PI3KC3-C2) and a late autophagy/endolysosomal trafficking factor. It binds Beclin 1/PIK3C3 complex machinery, supports PI3P-dependent autophagosome maturation, and coordinates HOPS/class C VPS and SNARE-dependent fusion events at autophagosomes and endosomes. UVRAG also has supported but non-core roles in Golgi-ER retrograde trafficking, degradative endocytic traffic, cytokinesis, and autophagy-independent DNA repair/centrosome stability.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0000323 lytic vacuole | IBA GO_REF:0000033 | MODIFY | Summary: Lytic vacuole is a non-human/generalized ancestor for UVRAG lysosome/endolysosomal localization. Reason: For human UVRAG, lysosome, late endosome, and autophagosome/autophagosome membrane are more precise locations for the late autophagy and endosomal trafficking role. Supporting Evidence: file:human/UVRAG/UVRAG-uniprot.txt Late endosome {ECO:0000269|PubMed:18843052} file:human/UVRAG/UVRAG-uniprot.txt Cytoplasmic vesicle, autophagosome file:human/UVRAG/UVRAG-uniprot.txt Early endosome {ECO:0000269|PubMed:18552835 |
| GO:0000149 SNARE binding | IBA GO_REF:0000033 | ACCEPT | Summary: SNARE binding is supported for UVRAG in late endosomal/autophagosome fusion contexts. Reason: UVRAG interacts with endosomal SNARE machinery and promotes fusogenic SNARE complex formation with class C VPS/HOPS-associated trafficking machinery. Supporting Evidence: PMID:24550300 interactions with the class C vacuolar protein sorting (C-Vps) tethering complex and endosomal PMID:24550300 by assembling a specific fusogenic SNARE complex file:human/UVRAG/UVRAG-uniprot.txt SNARE complex and promotes fusogenic SNARE complex formation during |
| GO:0035493 SNARE complex assembly | IBA GO_REF:0000033 | ACCEPT | Summary: SNARE complex assembly captures a specific UVRAG role in late endosomal/autophagosome fusion machinery. Reason: UVRAG promotes fusogenic SNARE complex formation in class C VPS/HOPS-dependent membrane fusion, making this more informative than generic protein binding. Supporting Evidence: PMID:24550300 interactions with the class C vacuolar protein sorting (C-Vps) tethering complex and endosomal PMID:24550300 by assembling a specific fusogenic SNARE complex file:human/UVRAG/UVRAG-uniprot.txt SNARE complex and promotes fusogenic SNARE complex formation during |
| GO:0000775 chromosome, centromeric region | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: Centromeric/chromosome localization is experimentally tied to UVRAG genome-stability biology but is not PN core. Reason: UVRAG has an autophagy-independent DNA repair and chromosome/centrosome stability branch. Retain as non-core relative to class III PI3K/autophagosome maturation biology. Supporting Evidence: PMID:22542840 UVRAG promotes DNA double-strand-break repair by directly binding and activating PMID:22542840 centrosome instability and aneuploidy file:human/UVRAG/UVRAG-uniprot.txt Promotes DNA double-strand break (DSB) repair by association with DNA-dependent |
| GO:0005764 lysosome | IEA GO_REF:0000044 | ACCEPT | Summary: Lysosome localization is compatible with UVRAG late autophagy/endolysosomal trafficking. Reason: UVRAG functions in autophagosome fusion with late endosomes/lysosomes and endocytic cargo delivery to degradative compartments. Supporting Evidence: PMID:18552835 autophagosome fusion with late endosomes/lysosomes file:human/UVRAG/UVRAG-uniprot.txt Lysosome {ECO:0000269|PubMed:18843052} |
| GO:0005769 early endosome | IEA GO_REF:0000044 | ACCEPT | Summary: Early endosome localization is supported for UVRAG endosomal trafficking biology. Reason: UVRAG is found on endosomal compartments and contributes to endosome/endosome fusion and degradative endocytic trafficking. Supporting Evidence: PMID:18552835 endosome-endosome fusion, resulting in rapid degradation of endocytic cargo file:human/UVRAG/UVRAG-uniprot.txt Early endosome {ECO:0000269|PubMed:18552835 |
| GO:0005770 late endosome | IEA GO_REF:0000044 | ACCEPT | Summary: Late endosome localization is supported and relevant to UVRAG autophagosome/endosome maturation. Reason: The UVRAG-class C VPS/HOPS axis promotes autophagosome fusion with late endosomes/lysosomes and late endocytic fusion. Supporting Evidence: PMID:18552835 autophagosome fusion with late endosomes/lysosomes file:human/UVRAG/UVRAG-uniprot.txt Late endosome {ECO:0000269|PubMed:18843052} |
| GO:0005776 autophagosome | IEA GO_REF:0000044 | ACCEPT | Summary: Autophagosome localization is directly relevant to UVRAG/PACER-mediated autophagosome maturation. Reason: UVRAG is recruited to autophagosome-associated structures and participates in PI3KC3/HOPS activation during autophagosome maturation. Supporting Evidence: PMID:28306502 Pacer recruits PI3KC3 and HOPS complexes to the autophagosome file:human/UVRAG/UVRAG-uniprot.txt Cytoplasmic vesicle, autophagosome |
| GO:0005783 endoplasmic reticulum | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: Endoplasmic reticulum localization is supported for the RINT1/NRZ retrograde trafficking branch. Reason: UVRAG has a PtdIns(3)P-dependent ER tethering and Golgi-ER retrograde transport role. This is supported but secondary to the PN class III PI3K/autophagosome maturation focus. Supporting Evidence: PMID:24056303 PtdIns(3)P)-binding protein PMID:24056303 acts as an integral component of the RINT-1-containing ER tethering complex PMID:24056303 Bif-1-beclin-1-PI(3)KC3 complex to mobilize Atg9 translocation |
| GO:0006914 autophagy | IEA GO_REF:0000117 | MODIFY | Summary: Broad autophagy is directionally correct but should be narrowed to UVRAG autophagosome maturation/positive autophagy regulation. Reason: UVRAG regulates class III PI3K/HOPS-dependent autophagosome maturation and Beclin1-PI3KC3 autophagy signaling; the parent autophagy term loses that specificity. Proposed replacements: autophagosome maturation positive regulation of autophagy Supporting Evidence: PMID:16799551 positive regulator of the Beclin1-PI(3)KC3 complex PMID:18843052 Atg14, and UVRAG are not present in the same complex file:human/UVRAG/UVRAG-uniprot.txt acts as a regulatory subunit of the alternative PI3K complex II file:human/UVRAG/UVRAG-uniprot.txt mediates formation of phosphatidylinositol 3-phosphate PMID:18552835 interacts with the class C Vps complex PMID:18552835 autophagosome fusion with late endosomes/lysosomes |
| GO:0016192 vesicle-mediated transport | IEA GO_REF:0000117 | MODIFY | Summary: Vesicle-mediated transport is too broad for UVRAG; the supported processes are Golgi-ER retrograde transport and endolysosomal/autophagic trafficking. Reason: UVRAG couples PtdIns(3)P-dependent ER tethering, ATG9 transport, endosome fusion, and autophagosome maturation. More specific transport terms should be used instead of the broad parent. Proposed replacements: retrograde vesicle-mediated transport, Golgi to endoplasmic reticulum multivesicular body sorting pathway autophagosome maturation Supporting Evidence: PMID:18552835 interacts with the class C Vps complex PMID:18552835 autophagosome fusion with late endosomes/lysosomes PMID:24056303 PtdIns(3)P)-binding protein PMID:24056303 acts as an integral component of the RINT-1-containing ER tethering complex PMID:24056303 Bif-1-beclin-1-PI(3)KC3 complex to mobilize Atg9 translocation |
| GO:0030496 midbody | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: Midbody localization is supported for UVRAG cytokinesis biology but is not PN core. Reason: The PI3KC3-C2/BIF-1-containing subcomplex has a supported cytokinesis/midbody branch; retain it as non-core relative to autophagosome maturation. Supporting Evidence: PMID:20643123 strong localisation of these proteins to the midbody file:human/UVRAG/UVRAG-uniprot.txt Midbody |
| GO:0031410 cytoplasmic vesicle | IEA GO_REF:0000117 | MODIFY | Summary: Cytoplasmic vesicle is true but too broad for UVRAG localization. Reason: UVRAG is better localized to autophagosome/autophagosome membrane and early/late endosome compartments relevant to PI3KC3-C2 and HOPS/SNARE trafficking. Supporting Evidence: file:human/UVRAG/UVRAG-uniprot.txt Late endosome {ECO:0000269|PubMed:18843052} file:human/UVRAG/UVRAG-uniprot.txt Cytoplasmic vesicle, autophagosome file:human/UVRAG/UVRAG-uniprot.txt Early endosome {ECO:0000269|PubMed:18552835 |
| GO:0036092 phosphatidylinositol-3-phosphate biosynthetic process | IEA GO_REF:0000117 | ACCEPT | Summary: UVRAG is involved in PI3P biosynthesis as a PI3KC3-C2 regulatory subunit rather than as the lipid kinase itself. Reason: UVRAG activates/regulates PIK3C3/VPS34 within PI3KC3-C2, which mediates formation of phosphatidylinositol 3-phosphate during autophagy/endosomal trafficking. Supporting Evidence: PMID:16799551 positive regulator of the Beclin1-PI(3)KC3 complex PMID:18843052 Atg14, and UVRAG are not present in the same complex file:human/UVRAG/UVRAG-uniprot.txt acts as a regulatory subunit of the alternative PI3K complex II file:human/UVRAG/UVRAG-uniprot.txt mediates formation of phosphatidylinositol 3-phosphate |
| GO:0043933 protein-containing complex organization | IEA GO_REF:0000117 | MODIFY | Summary: Protein-containing complex organization is too broad for UVRAG; SNARE/HOPS and PI3KC3-C2 complex roles are more specific. Reason: UVRAG participates in specific PI3KC3-C2, HOPS/class C VPS, and SNARE assembly contexts. Generic complex organization should be replaced by the specific supported complex/process annotations. Proposed replacements: SNARE complex assembly phosphatidylinositol 3-kinase complex, class III, type II Supporting Evidence: PMID:24550300 interactions with the class C vacuolar protein sorting (C-Vps) tethering complex and endosomal PMID:24550300 by assembling a specific fusogenic SNARE complex file:human/UVRAG/UVRAG-uniprot.txt SNARE complex and promotes fusogenic SNARE complex formation during PMID:16799551 positive regulator of the Beclin1-PI(3)KC3 complex PMID:18843052 Atg14, and UVRAG are not present in the same complex |
| GO:0005515 protein binding | IPI PMID:17891140 Bif-1 interacts with Beclin 1 through UVRAG and regulates au... | MARK AS OVER ANNOTATED | Summary: The interaction evidence may be real, but generic protein binding is not an informative UVRAG function. Reason: UVRAG has specific complex/adaptor roles in PI3KC3-C2, HOPS/class C VPS, SNARE, DNA-PK, and other assemblies. Retaining protein binding obscures the biological function and should be replaced by specific complex membership or binding terms where curatable. Supporting Evidence: file:human/UVRAG/UVRAG-uniprot.txt Component of the PI3K (PI3KC3/PI3K-III/class III file:human/UVRAG/UVRAG-uniprot.txt Interacts with VPS16; VPS11; VPS18; VPS33 file:human/UVRAG/UVRAG-uniprot.txt Interacts with PRKDC, XRCC6 and XRCC5 |
| GO:0005515 protein binding | IPI PMID:19050071 Identification of Barkor as a mammalian autophagy-specific f... | MARK AS OVER ANNOTATED | Summary: The interaction evidence may be real, but generic protein binding is not an informative UVRAG function. Reason: UVRAG has specific complex/adaptor roles in PI3KC3-C2, HOPS/class C VPS, SNARE, DNA-PK, and other assemblies. Retaining protein binding obscures the biological function and should be replaced by specific complex membership or binding terms where curatable. Supporting Evidence: file:human/UVRAG/UVRAG-uniprot.txt Component of the PI3K (PI3KC3/PI3K-III/class III file:human/UVRAG/UVRAG-uniprot.txt Interacts with VPS16; VPS11; VPS18; VPS33 file:human/UVRAG/UVRAG-uniprot.txt Interacts with PRKDC, XRCC6 and XRCC5 |
| GO:0005515 protein binding | IPI PMID:20562859 Network organization of the human autophagy system. | MARK AS OVER ANNOTATED | Summary: The interaction evidence may be real, but generic protein binding is not an informative UVRAG function. Reason: UVRAG has specific complex/adaptor roles in PI3KC3-C2, HOPS/class C VPS, SNARE, DNA-PK, and other assemblies. Retaining protein binding obscures the biological function and should be replaced by specific complex membership or binding terms where curatable. Supporting Evidence: file:human/UVRAG/UVRAG-uniprot.txt Component of the PI3K (PI3KC3/PI3K-III/class III file:human/UVRAG/UVRAG-uniprot.txt Interacts with VPS16; VPS11; VPS18; VPS33 file:human/UVRAG/UVRAG-uniprot.txt Interacts with PRKDC, XRCC6 and XRCC5 |
| GO:0005515 protein binding | IPI PMID:21062745 The RUN domain of rubicon is important for hVps34 binding, l... | MARK AS OVER ANNOTATED | Summary: The interaction evidence may be real, but generic protein binding is not an informative UVRAG function. Reason: UVRAG has specific complex/adaptor roles in PI3KC3-C2, HOPS/class C VPS, SNARE, DNA-PK, and other assemblies. Retaining protein binding obscures the biological function and should be replaced by specific complex membership or binding terms where curatable. Supporting Evidence: file:human/UVRAG/UVRAG-uniprot.txt Component of the PI3K (PI3KC3/PI3K-III/class III file:human/UVRAG/UVRAG-uniprot.txt Interacts with VPS16; VPS11; VPS18; VPS33 file:human/UVRAG/UVRAG-uniprot.txt Interacts with PRKDC, XRCC6 and XRCC5 |
| GO:0005515 protein binding | IPI PMID:21597469 UV irradiation resistance-associated gene suppresses apoptos... | MARK AS OVER ANNOTATED | Summary: The interaction evidence may be real, but generic protein binding is not an informative UVRAG function. Reason: UVRAG has specific complex/adaptor roles in PI3KC3-C2, HOPS/class C VPS, SNARE, DNA-PK, and other assemblies. Retaining protein binding obscures the biological function and should be replaced by specific complex membership or binding terms where curatable. Supporting Evidence: file:human/UVRAG/UVRAG-uniprot.txt Component of the PI3K (PI3KC3/PI3K-III/class III file:human/UVRAG/UVRAG-uniprot.txt Interacts with VPS16; VPS11; VPS18; VPS33 file:human/UVRAG/UVRAG-uniprot.txt Interacts with PRKDC, XRCC6 and XRCC5 |
| GO:0005515 protein binding | IPI PMID:22081109 Inhibition of autophagy by TAB2 and TAB3. | MARK AS OVER ANNOTATED | Summary: The interaction evidence may be real, but generic protein binding is not an informative UVRAG function. Reason: UVRAG has specific complex/adaptor roles in PI3KC3-C2, HOPS/class C VPS, SNARE, DNA-PK, and other assemblies. Retaining protein binding obscures the biological function and should be replaced by specific complex membership or binding terms where curatable. Supporting Evidence: file:human/UVRAG/UVRAG-uniprot.txt Component of the PI3K (PI3KC3/PI3K-III/class III file:human/UVRAG/UVRAG-uniprot.txt Interacts with VPS16; VPS11; VPS18; VPS33 file:human/UVRAG/UVRAG-uniprot.txt Interacts with PRKDC, XRCC6 and XRCC5 |
| GO:0005515 protein binding | IPI PMID:22493499 Receptor signaling lymphocyte-activation molecule family 1 (... | MARK AS OVER ANNOTATED | Summary: The interaction evidence may be real, but generic protein binding is not an informative UVRAG function. Reason: UVRAG has specific complex/adaptor roles in PI3KC3-C2, HOPS/class C VPS, SNARE, DNA-PK, and other assemblies. Retaining protein binding obscures the biological function and should be replaced by specific complex membership or binding terms where curatable. Supporting Evidence: file:human/UVRAG/UVRAG-uniprot.txt Component of the PI3K (PI3KC3/PI3K-III/class III file:human/UVRAG/UVRAG-uniprot.txt Interacts with VPS16; VPS11; VPS18; VPS33 file:human/UVRAG/UVRAG-uniprot.txt Interacts with PRKDC, XRCC6 and XRCC5 |
| GO:0005515 protein binding | IPI PMID:23954414 Beclin 2 functions in autophagy, degradation of G protein-co... | MARK AS OVER ANNOTATED | Summary: The interaction evidence may be real, but generic protein binding is not an informative UVRAG function. Reason: UVRAG has specific complex/adaptor roles in PI3KC3-C2, HOPS/class C VPS, SNARE, DNA-PK, and other assemblies. Retaining protein binding obscures the biological function and should be replaced by specific complex membership or binding terms where curatable. Supporting Evidence: file:human/UVRAG/UVRAG-uniprot.txt Component of the PI3K (PI3KC3/PI3K-III/class III file:human/UVRAG/UVRAG-uniprot.txt Interacts with VPS16; VPS11; VPS18; VPS33 file:human/UVRAG/UVRAG-uniprot.txt Interacts with PRKDC, XRCC6 and XRCC5 |
| GO:0005515 protein binding | IPI PMID:24034250 EGFR-mediated Beclin 1 phosphorylation in autophagy suppress... | MARK AS OVER ANNOTATED | Summary: The interaction evidence may be real, but generic protein binding is not an informative UVRAG function. Reason: UVRAG has specific complex/adaptor roles in PI3KC3-C2, HOPS/class C VPS, SNARE, DNA-PK, and other assemblies. Retaining protein binding obscures the biological function and should be replaced by specific complex membership or binding terms where curatable. Supporting Evidence: file:human/UVRAG/UVRAG-uniprot.txt Component of the PI3K (PI3KC3/PI3K-III/class III file:human/UVRAG/UVRAG-uniprot.txt Interacts with VPS16; VPS11; VPS18; VPS33 file:human/UVRAG/UVRAG-uniprot.txt Interacts with PRKDC, XRCC6 and XRCC5 |
| GO:0005515 protein binding | IPI PMID:24056303 PtdIns(3)P-bound UVRAG coordinates Golgi-ER retrograde and A... | MARK AS OVER ANNOTATED | Summary: The interaction evidence may be real, but generic protein binding is not an informative UVRAG function. Reason: UVRAG has specific complex/adaptor roles in PI3KC3-C2, HOPS/class C VPS, SNARE, DNA-PK, and other assemblies. Retaining protein binding obscures the biological function and should be replaced by specific complex membership or binding terms where curatable. Supporting Evidence: file:human/UVRAG/UVRAG-uniprot.txt Component of the PI3K (PI3KC3/PI3K-III/class III file:human/UVRAG/UVRAG-uniprot.txt Interacts with VPS16; VPS11; VPS18; VPS33 file:human/UVRAG/UVRAG-uniprot.txt Interacts with PRKDC, XRCC6 and XRCC5 |
| GO:0005515 protein binding | IPI PMID:24554770 The HOPS complex mediates autophagosome-lysosome fusion thro... | MARK AS OVER ANNOTATED | Summary: The interaction evidence may be real, but generic protein binding is not an informative UVRAG function. Reason: UVRAG has specific complex/adaptor roles in PI3KC3-C2, HOPS/class C VPS, SNARE, DNA-PK, and other assemblies. Retaining protein binding obscures the biological function and should be replaced by specific complex membership or binding terms where curatable. Supporting Evidence: file:human/UVRAG/UVRAG-uniprot.txt Component of the PI3K (PI3KC3/PI3K-III/class III file:human/UVRAG/UVRAG-uniprot.txt Interacts with VPS16; VPS11; VPS18; VPS33 file:human/UVRAG/UVRAG-uniprot.txt Interacts with PRKDC, XRCC6 and XRCC5 |
| GO:0005515 protein binding | IPI PMID:24785657 NRBF2 regulates macroautophagy as a component of Vps34 Compl... | MARK AS OVER ANNOTATED | Summary: The interaction evidence may be real, but generic protein binding is not an informative UVRAG function. Reason: UVRAG has specific complex/adaptor roles in PI3KC3-C2, HOPS/class C VPS, SNARE, DNA-PK, and other assemblies. Retaining protein binding obscures the biological function and should be replaced by specific complex membership or binding terms where curatable. Supporting Evidence: file:human/UVRAG/UVRAG-uniprot.txt Component of the PI3K (PI3KC3/PI3K-III/class III file:human/UVRAG/UVRAG-uniprot.txt Interacts with VPS16; VPS11; VPS18; VPS33 file:human/UVRAG/UVRAG-uniprot.txt Interacts with PRKDC, XRCC6 and XRCC5 |
| GO:0005515 protein binding | IPI PMID:24849286 NRBF2 regulates autophagy and prevents liver injury by modul... | MARK AS OVER ANNOTATED | Summary: The interaction evidence may be real, but generic protein binding is not an informative UVRAG function. Reason: UVRAG has specific complex/adaptor roles in PI3KC3-C2, HOPS/class C VPS, SNARE, DNA-PK, and other assemblies. Retaining protein binding obscures the biological function and should be replaced by specific complex membership or binding terms where curatable. Supporting Evidence: file:human/UVRAG/UVRAG-uniprot.txt Component of the PI3K (PI3KC3/PI3K-III/class III file:human/UVRAG/UVRAG-uniprot.txt Interacts with VPS16; VPS11; VPS18; VPS33 file:human/UVRAG/UVRAG-uniprot.txt Interacts with PRKDC, XRCC6 and XRCC5 |
| GO:0005515 protein binding | IPI PMID:25490155 Architecture and dynamics of the autophagic phosphatidylinos... | MARK AS OVER ANNOTATED | Summary: The interaction evidence may be real, but generic protein binding is not an informative UVRAG function. Reason: UVRAG has specific complex/adaptor roles in PI3KC3-C2, HOPS/class C VPS, SNARE, DNA-PK, and other assemblies. Retaining protein binding obscures the biological function and should be replaced by specific complex membership or binding terms where curatable. Supporting Evidence: file:human/UVRAG/UVRAG-uniprot.txt Component of the PI3K (PI3KC3/PI3K-III/class III file:human/UVRAG/UVRAG-uniprot.txt Interacts with VPS16; VPS11; VPS18; VPS33 file:human/UVRAG/UVRAG-uniprot.txt Interacts with PRKDC, XRCC6 and XRCC5 |
| GO:0005515 protein binding | IPI PMID:26496610 A human interactome in three quantitative dimensions organiz... | MARK AS OVER ANNOTATED | Summary: The interaction evidence may be real, but generic protein binding is not an informative UVRAG function. Reason: UVRAG has specific complex/adaptor roles in PI3KC3-C2, HOPS/class C VPS, SNARE, DNA-PK, and other assemblies. Retaining protein binding obscures the biological function and should be replaced by specific complex membership or binding terms where curatable. Supporting Evidence: file:human/UVRAG/UVRAG-uniprot.txt Component of the PI3K (PI3KC3/PI3K-III/class III file:human/UVRAG/UVRAG-uniprot.txt Interacts with VPS16; VPS11; VPS18; VPS33 file:human/UVRAG/UVRAG-uniprot.txt Interacts with PRKDC, XRCC6 and XRCC5 |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | MARK AS OVER ANNOTATED | Summary: The interaction evidence may be real, but generic protein binding is not an informative UVRAG function. Reason: UVRAG has specific complex/adaptor roles in PI3KC3-C2, HOPS/class C VPS, SNARE, DNA-PK, and other assemblies. Retaining protein binding obscures the biological function and should be replaced by specific complex membership or binding terms where curatable. Supporting Evidence: file:human/UVRAG/UVRAG-uniprot.txt Component of the PI3K (PI3KC3/PI3K-III/class III file:human/UVRAG/UVRAG-uniprot.txt Interacts with VPS16; VPS11; VPS18; VPS33 file:human/UVRAG/UVRAG-uniprot.txt Interacts with PRKDC, XRCC6 and XRCC5 |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | MARK AS OVER ANNOTATED | Summary: The interaction evidence may be real, but generic protein binding is not an informative UVRAG function. Reason: UVRAG has specific complex/adaptor roles in PI3KC3-C2, HOPS/class C VPS, SNARE, DNA-PK, and other assemblies. Retaining protein binding obscures the biological function and should be replaced by specific complex membership or binding terms where curatable. Supporting Evidence: file:human/UVRAG/UVRAG-uniprot.txt Component of the PI3K (PI3KC3/PI3K-III/class III file:human/UVRAG/UVRAG-uniprot.txt Interacts with VPS16; VPS11; VPS18; VPS33 file:human/UVRAG/UVRAG-uniprot.txt Interacts with PRKDC, XRCC6 and XRCC5 |
| GO:0005515 protein binding | IPI PMID:34386498 ORF3a-Mediated Incomplete Autophagy Facilitates Severe Acute... | MARK AS OVER ANNOTATED | Summary: The interaction evidence may be real, but generic protein binding is not an informative UVRAG function. Reason: UVRAG has specific complex/adaptor roles in PI3KC3-C2, HOPS/class C VPS, SNARE, DNA-PK, and other assemblies. Retaining protein binding obscures the biological function and should be replaced by specific complex membership or binding terms where curatable. Supporting Evidence: file:human/UVRAG/UVRAG-uniprot.txt Component of the PI3K (PI3KC3/PI3K-III/class III file:human/UVRAG/UVRAG-uniprot.txt Interacts with VPS16; VPS11; VPS18; VPS33 file:human/UVRAG/UVRAG-uniprot.txt Interacts with PRKDC, XRCC6 and XRCC5 |
| GO:0005515 protein binding | IPI PMID:35044719 Proteome-scale mapping of binding sites in the unstructured ... | MARK AS OVER ANNOTATED | Summary: The interaction evidence may be real, but generic protein binding is not an informative UVRAG function. Reason: UVRAG has specific complex/adaptor roles in PI3KC3-C2, HOPS/class C VPS, SNARE, DNA-PK, and other assemblies. Retaining protein binding obscures the biological function and should be replaced by specific complex membership or binding terms where curatable. Supporting Evidence: file:human/UVRAG/UVRAG-uniprot.txt Component of the PI3K (PI3KC3/PI3K-III/class III file:human/UVRAG/UVRAG-uniprot.txt Interacts with VPS16; VPS11; VPS18; VPS33 file:human/UVRAG/UVRAG-uniprot.txt Interacts with PRKDC, XRCC6 and XRCC5 |
| GO:0005515 protein binding | IPI PMID:35271311 OpenCell: Endogenous tagging for the cartography of human ce... | MARK AS OVER ANNOTATED | Summary: The interaction evidence may be real, but generic protein binding is not an informative UVRAG function. Reason: UVRAG has specific complex/adaptor roles in PI3KC3-C2, HOPS/class C VPS, SNARE, DNA-PK, and other assemblies. Retaining protein binding obscures the biological function and should be replaced by specific complex membership or binding terms where curatable. Supporting Evidence: file:human/UVRAG/UVRAG-uniprot.txt Component of the PI3K (PI3KC3/PI3K-III/class III file:human/UVRAG/UVRAG-uniprot.txt Interacts with VPS16; VPS11; VPS18; VPS33 file:human/UVRAG/UVRAG-uniprot.txt Interacts with PRKDC, XRCC6 and XRCC5 |
| GO:0005515 protein binding | IPI PMID:37219487 Large-scale phosphomimetic screening identifies phospho-modu... | MARK AS OVER ANNOTATED | Summary: The interaction evidence may be real, but generic protein binding is not an informative UVRAG function. Reason: UVRAG has specific complex/adaptor roles in PI3KC3-C2, HOPS/class C VPS, SNARE, DNA-PK, and other assemblies. Retaining protein binding obscures the biological function and should be replaced by specific complex membership or binding terms where curatable. Supporting Evidence: file:human/UVRAG/UVRAG-uniprot.txt Component of the PI3K (PI3KC3/PI3K-III/class III file:human/UVRAG/UVRAG-uniprot.txt Interacts with VPS16; VPS11; VPS18; VPS33 file:human/UVRAG/UVRAG-uniprot.txt Interacts with PRKDC, XRCC6 and XRCC5 |
| GO:0000149 SNARE binding | IEA GO_REF:0000107 | ACCEPT | Summary: SNARE binding is supported for UVRAG in late endosomal/autophagosome fusion contexts. Reason: UVRAG interacts with endosomal SNARE machinery and promotes fusogenic SNARE complex formation with class C VPS/HOPS-associated trafficking machinery. Supporting Evidence: PMID:24550300 interactions with the class C vacuolar protein sorting (C-Vps) tethering complex and endosomal PMID:24550300 by assembling a specific fusogenic SNARE complex file:human/UVRAG/UVRAG-uniprot.txt SNARE complex and promotes fusogenic SNARE complex formation during |
| GO:0006281 DNA repair | IEA GO_REF:0000120 | KEEP AS NON CORE | Summary: DNA repair is supported for UVRAG but is an autophagy-independent non-core branch in this PN review. Reason: The strongest evidence supports UVRAG activation of DNA-PK in NHEJ and chromosomal stability, but this should not be treated as the proteostasis/autophagy core function. Supporting Evidence: PMID:22542840 UVRAG promotes DNA double-strand-break repair by directly binding and activating PMID:22542840 centrosome instability and aneuploidy file:human/UVRAG/UVRAG-uniprot.txt Promotes DNA double-strand break (DSB) repair by association with DNA-dependent |
| GO:0007051 spindle organization | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Spindle organization is a non-core inference from UVRAG centrosome/chromosome stability biology. Reason: The paper supports proper chromosome segregation and centrosome stability, but this is outside the class III PI3K/autophagosome maturation core. Supporting Evidence: PMID:22542840 UVRAG promotes DNA double-strand-break repair by directly binding and activating PMID:22542840 centrosome instability and aneuploidy file:human/UVRAG/UVRAG-uniprot.txt Promotes DNA double-strand break (DSB) repair by association with DNA-dependent |
| GO:0007059 chromosome segregation | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Chromosome segregation is supported by UVRAG centrosome/chromosome stability evidence but is non-core. Reason: UVRAG disruption causes centrosome instability and aneuploidy; retain as non-core genome-stability biology. Supporting Evidence: PMID:22542840 UVRAG promotes DNA double-strand-break repair by directly binding and activating PMID:22542840 centrosome instability and aneuploidy file:human/UVRAG/UVRAG-uniprot.txt Promotes DNA double-strand break (DSB) repair by association with DNA-dependent |
| GO:0007098 centrosome cycle | IEA GO_REF:0000120 | KEEP AS NON CORE | Summary: Centrosome cycle is supported as a non-core centrosome stability/chromosome segregation branch. Reason: UVRAG interacts with CEP63 and is required for centrosome stability, but this is separate from the PN autophagy/endolysosomal core. Supporting Evidence: PMID:22542840 UVRAG promotes DNA double-strand-break repair by directly binding and activating PMID:22542840 centrosome instability and aneuploidy file:human/UVRAG/UVRAG-uniprot.txt Promotes DNA double-strand break (DSB) repair by association with DNA-dependent |
| GO:0017124 SH3 domain binding | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: SH3 domain binding is compatible with the SH3GLB1/Bif-1 interaction but is not the core UVRAG function. Reason: The SH3GLB1 interaction helps connect UVRAG to BECN1/PI3KC3-C2, but the more informative annotations are PI3KC3-C2 membership and autophagosome/endosomal trafficking roles. Supporting Evidence: PMID:17891140 Bif-1 interacts with Beclin 1 through UVRAG file:human/UVRAG/UVRAG-uniprot.txt Interacts with SH3GLB1 |
| GO:0032991 protein-containing complex | IEA GO_REF:0000120 | MODIFY | Summary: Protein-containing complex is correct but too generic for UVRAG. Reason: UVRAG is a component/regulatory subunit of the UVRAG-containing PI3KC3-C2 complex; the generic complex term should be narrowed to the type II class III PI3K complex. Proposed replacements: phosphatidylinositol 3-kinase complex, class III, type II Supporting Evidence: PMID:16799551 positive regulator of the Beclin1-PI(3)KC3 complex PMID:18843052 Atg14, and UVRAG are not present in the same complex file:human/UVRAG/UVRAG-uniprot.txt acts as a regulatory subunit of the alternative PI3K complex II file:human/UVRAG/UVRAG-uniprot.txt mediates formation of phosphatidylinositol 3-phosphate |
| GO:0045335 phagocytic vesicle | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Phagocytic vesicle context is supported through SLAMF1/Vps34/Beclin1/UVRAG phagosome signaling but is non-core. Reason: This is a macrophage/phagosome-specific branch of UVRAG-containing class III PI3K signaling rather than the central autophagosome maturation role. Supporting Evidence: PMID:22493499 Slamf1 interacts with the class III PI3K Vps34 in a complex with Beclin-1 and UVRAG PMID:22493499 Slamf1 recruits a subset of Vps34-associated proteins |
| GO:0010506 regulation of autophagy | IDA PMID:16799551 Autophagic and tumour suppressor activity of a novel Beclin1... | MODIFY | Summary: UVRAG positively regulates Beclin1-PI3KC3 autophagy activity, so the undirected regulation term should be narrowed. Reason: The cited evidence presents UVRAG as a positive regulator/activator of the Beclin1-PI3KC3 complex and autophagy, not merely an unspecified regulator. Proposed replacements: positive regulation of autophagy autophagosome maturation Supporting Evidence: PMID:16799551 positive regulator of the Beclin1-PI(3)KC3 complex PMID:16799551 UVRAG-mediated activation of the Beclin1-PI(3)KC3 complex promotes autophagy |
| GO:0035032 phosphatidylinositol 3-kinase complex, class III | IPI PMID:25490155 Architecture and dynamics of the autophagic phosphatidylinos... | MODIFY | Summary: Generic class III PI3K complex membership is correct but underspecified for UVRAG. Reason: UVRAG defines the type II/PI3KC3-C2 branch rather than the ATG14-containing type I complex. The GO term should be narrowed to class III PI3K complex type II. Proposed replacements: phosphatidylinositol 3-kinase complex, class III, type II Supporting Evidence: PMID:16799551 positive regulator of the Beclin1-PI(3)KC3 complex PMID:18843052 Atg14, and UVRAG are not present in the same complex file:human/UVRAG/UVRAG-uniprot.txt acts as a regulatory subunit of the alternative PI3K complex II file:human/UVRAG/UVRAG-uniprot.txt mediates formation of phosphatidylinositol 3-phosphate |
| GO:0036092 phosphatidylinositol-3-phosphate biosynthetic process | IDA PMID:8999962 Characterization of p150, an adaptor protein for the human p... | ACCEPT | Summary: UVRAG is involved in PI3P biosynthesis as a PI3KC3-C2 regulatory subunit rather than as the lipid kinase itself. Reason: UVRAG activates/regulates PIK3C3/VPS34 within PI3KC3-C2, which mediates formation of phosphatidylinositol 3-phosphate during autophagy/endosomal trafficking. Supporting Evidence: PMID:16799551 positive regulator of the Beclin1-PI(3)KC3 complex PMID:18843052 Atg14, and UVRAG are not present in the same complex file:human/UVRAG/UVRAG-uniprot.txt acts as a regulatory subunit of the alternative PI3K complex II file:human/UVRAG/UVRAG-uniprot.txt mediates formation of phosphatidylinositol 3-phosphate |
| GO:0005769 early endosome | EXP PMID:18552835 Beclin1-binding UVRAG targets the class C Vps complex to coo... | ACCEPT | Summary: Early endosome localization is supported for UVRAG endosomal trafficking biology. Reason: UVRAG is found on endosomal compartments and contributes to endosome/endosome fusion and degradative endocytic trafficking. Supporting Evidence: PMID:18552835 endosome-endosome fusion, resulting in rapid degradation of endocytic cargo file:human/UVRAG/UVRAG-uniprot.txt Early endosome {ECO:0000269|PubMed:18552835 |
| GO:0033116 endoplasmic reticulum-Golgi intermediate compartment membrane | TAS Reactome:R-HSA-9730505 | MARK AS OVER ANNOTATED | Summary: ERGIC membrane is a virus-event-specific Reactome localization and is too specific for general UVRAG biology. Reason: The Reactome event records SARS-CoV-2 3a binding to UVRAG and disruption of a Beclin1:VPS34:UVRAG complex; it does not establish ERGIC membrane as a stable UVRAG cellular component. ER and autophagosome/endosome locations are better supported. Supporting Evidence: Reactome:R-HSA-9730505 SARS-CoV-2 3a binds to UVRAG file:human/UVRAG/UVRAG-uniprot.txt Endoplasmic reticulum {ECO:0000269|PubMed:24056303} |
| GO:0000421 autophagosome membrane | IDA PMID:28306502 Pacer Mediates the Function of Class III PI3K and HOPS Compl... | ACCEPT | Summary: Autophagosome membrane localization is directly supported for UVRAG/PACER-mediated maturation. Reason: UVRAG is recruited to autophagosomes through RUBCNL/PACER and supports local PI3KC3/HOPS activity for autophagosome maturation. Supporting Evidence: PMID:28306502 Pacer recruits PI3KC3 and HOPS complexes to the autophagosome file:human/UVRAG/UVRAG-uniprot.txt Recruited to autophagosome following interaction with RUBCNL/PACER |
| GO:0005515 protein binding | IPI PMID:28306502 Pacer Mediates the Function of Class III PI3K and HOPS Compl... | MARK AS OVER ANNOTATED | Summary: The interaction evidence may be real, but generic protein binding is not an informative UVRAG function. Reason: UVRAG has specific complex/adaptor roles in PI3KC3-C2, HOPS/class C VPS, SNARE, DNA-PK, and other assemblies. Retaining protein binding obscures the biological function and should be replaced by specific complex membership or binding terms where curatable. Supporting Evidence: file:human/UVRAG/UVRAG-uniprot.txt Component of the PI3K (PI3KC3/PI3K-III/class III file:human/UVRAG/UVRAG-uniprot.txt Interacts with VPS16; VPS11; VPS18; VPS33 file:human/UVRAG/UVRAG-uniprot.txt Interacts with PRKDC, XRCC6 and XRCC5 |
| GO:0097352 autophagosome maturation | IDA PMID:28306502 Pacer Mediates the Function of Class III PI3K and HOPS Compl... | ACCEPT | Summary: Autophagosome maturation is a core UVRAG process. Reason: UVRAG coordinates PI3KC3/HOPS/class C VPS machinery and autophagosome-lysosome/endosome fusion during late autophagy. Supporting Evidence: PMID:18552835 interacts with the class C Vps complex PMID:18552835 autophagosome fusion with late endosomes/lysosomes PMID:28306502 Pacer recruits PI3KC3 and HOPS complexes to the autophagosome file:human/UVRAG/UVRAG-uniprot.txt Involved in maturation of autophagosomes and degradative endocytic trafficking PMID:25533187 UVRAG is released from RUBICON to interact with the HOPS complex |
| GO:0005515 protein binding | IPI PMID:28479384 Beclin1 antagonizes LAPTM4B-mediated EGFR overactivation in ... | MARK AS OVER ANNOTATED | Summary: The interaction evidence may be real, but generic protein binding is not an informative UVRAG function. Reason: UVRAG has specific complex/adaptor roles in PI3KC3-C2, HOPS/class C VPS, SNARE, DNA-PK, and other assemblies. Retaining protein binding obscures the biological function and should be replaced by specific complex membership or binding terms where curatable. Supporting Evidence: file:human/UVRAG/UVRAG-uniprot.txt Component of the PI3K (PI3KC3/PI3K-III/class III file:human/UVRAG/UVRAG-uniprot.txt Interacts with VPS16; VPS11; VPS18; VPS33 file:human/UVRAG/UVRAG-uniprot.txt Interacts with PRKDC, XRCC6 and XRCC5 |
| GO:1901098 positive regulation of autophagosome maturation | TAS PMID:21118109 The role of ESCRT proteins in fusion events involving lysoso... | ACCEPT | Summary: Positive regulation of autophagosome maturation is core and well supported. Reason: UVRAG enhances autophagosome/endosome maturation via HOPS/class C VPS engagement and is released from inhibitory RUBICON interaction upon dephosphorylation. Supporting Evidence: PMID:18552835 interacts with the class C Vps complex PMID:18552835 autophagosome fusion with late endosomes/lysosomes PMID:28306502 Pacer recruits PI3KC3 and HOPS complexes to the autophagosome file:human/UVRAG/UVRAG-uniprot.txt Involved in maturation of autophagosomes and degradative endocytic trafficking PMID:25533187 enhances autophagosome and endosome maturation |
| GO:0071985 multivesicular body sorting pathway | TAS PMID:21118109 The role of ESCRT proteins in fusion events involving lysoso... | KEEP AS NON CORE | Summary: Multivesicular body/endosomal sorting is supported but non-core in the PN autophagy review. Reason: UVRAG contributes to degradative endocytic trafficking and endosome fusion, but the PN core is PI3KC3-C2/autophagosome maturation. Supporting Evidence: PMID:18552835 endosome-endosome fusion, resulting in rapid degradation of endocytic cargo PMID:20643123 regulates both receptor degradation and cytokinesis |
| GO:0005813 centrosome | IDA PMID:22542840 A dual role for UVRAG in maintaining chromosomal stability i... | KEEP AS NON CORE | Summary: Centrosome localization is supported but non-core. Reason: UVRAG localizes to centrosomes and interacts with CEP63 in an autophagy-independent chromosome-stability branch. Supporting Evidence: PMID:22542840 UVRAG promotes DNA double-strand-break repair by directly binding and activating PMID:22542840 centrosome instability and aneuploidy file:human/UVRAG/UVRAG-uniprot.txt Promotes DNA double-strand break (DSB) repair by association with DNA-dependent |
| GO:0006281 DNA repair | IMP PMID:22542840 A dual role for UVRAG in maintaining chromosomal stability i... | KEEP AS NON CORE | Summary: DNA repair is supported for UVRAG but is an autophagy-independent non-core branch in this PN review. Reason: The strongest evidence supports UVRAG activation of DNA-PK in NHEJ and chromosomal stability, but this should not be treated as the proteostasis/autophagy core function. Supporting Evidence: PMID:22542840 UVRAG promotes DNA double-strand-break repair by directly binding and activating PMID:22542840 centrosome instability and aneuploidy file:human/UVRAG/UVRAG-uniprot.txt Promotes DNA double-strand break (DSB) repair by association with DNA-dependent |
| GO:0007098 centrosome cycle | IMP PMID:22542840 A dual role for UVRAG in maintaining chromosomal stability i... | KEEP AS NON CORE | Summary: Centrosome cycle is supported as a non-core centrosome stability/chromosome segregation branch. Reason: UVRAG interacts with CEP63 and is required for centrosome stability, but this is separate from the PN autophagy/endolysosomal core. Supporting Evidence: PMID:22542840 UVRAG promotes DNA double-strand-break repair by directly binding and activating PMID:22542840 centrosome instability and aneuploidy file:human/UVRAG/UVRAG-uniprot.txt Promotes DNA double-strand break (DSB) repair by association with DNA-dependent |
| GO:0070418 DNA-dependent protein kinase complex | IDA PMID:22542840 A dual role for UVRAG in maintaining chromosomal stability i... | KEEP AS NON CORE | Summary: DNA-PK complex colocalization/association is supported but non-core. Reason: UVRAG binds/activates DNA-PK for NHEJ, but this genome-stability function is outside the PN autophagosome maturation core. Supporting Evidence: PMID:22542840 UVRAG promotes DNA double-strand-break repair by directly binding and activating PMID:22542840 centrosome instability and aneuploidy file:human/UVRAG/UVRAG-uniprot.txt Promotes DNA double-strand break (DSB) repair by association with DNA-dependent |
| GO:0071900 regulation of protein serine/threonine kinase activity | IDA PMID:22542840 A dual role for UVRAG in maintaining chromosomal stability i... | KEEP AS NON CORE | Summary: Regulation of serine/threonine kinase activity is supported through DNA-PK activation but is broad and non-core. Reason: The specific supported kinase is DNA-PK in NHEJ; this should not be interpreted as a core proteostasis/autophagy function. Proposed replacements: double-strand break repair via classical nonhomologous end joining DNA repair Supporting Evidence: PMID:22542840 UVRAG promotes DNA double-strand-break repair by directly binding and activating PMID:22542840 centrosome instability and aneuploidy file:human/UVRAG/UVRAG-uniprot.txt Promotes DNA double-strand break (DSB) repair by association with DNA-dependent |
| GO:0097680 double-strand break repair via classical nonhomologous end joining | IDA PMID:22542840 A dual role for UVRAG in maintaining chromosomal stability i... | KEEP AS NON CORE | Summary: Classical NHEJ is supported for UVRAG but non-core. Reason: UVRAG promotes DNA-PK-dependent NHEJ and chromosome stability, but this is a separate autophagy-independent branch. Supporting Evidence: PMID:22542840 UVRAG promotes DNA double-strand-break repair by directly binding and activating PMID:22542840 centrosome instability and aneuploidy file:human/UVRAG/UVRAG-uniprot.txt Promotes DNA double-strand break (DSB) repair by association with DNA-dependent |
| GO:0030496 midbody | IDA PMID:20643123 A phosphatidylinositol 3-kinase class III sub-complex contai... | KEEP AS NON CORE | Summary: Midbody localization is supported for UVRAG cytokinesis biology but is not PN core. Reason: The PI3KC3-C2/BIF-1-containing subcomplex has a supported cytokinesis/midbody branch; retain it as non-core relative to autophagosome maturation. Supporting Evidence: PMID:20643123 strong localisation of these proteins to the midbody file:human/UVRAG/UVRAG-uniprot.txt Midbody |
| GO:0032465 regulation of cytokinesis | IMP PMID:20643123 A phosphatidylinositol 3-kinase class III sub-complex contai... | KEEP AS NON CORE | Summary: Regulation of cytokinesis is supported through the UVRAG/BIF-1 PI3KC3 subcomplex but non-core. Reason: The cytokinesis/midbody role is experimentally supported, but it is distinct from the PN autophagosome maturation function. Supporting Evidence: PMID:20643123 regulates both receptor degradation and cytokinesis PMID:20643123 strong localisation of these proteins to the midbody |
| GO:0032801 receptor catabolic process | IMP PMID:20643123 A phosphatidylinositol 3-kinase class III sub-complex contai... | KEEP AS NON CORE | Summary: Receptor catabolic process is supported but non-core. Reason: UVRAG-containing PI3KC3-C2/BIF-1 machinery regulates degradative endocytic traffic and receptor degradation, but this is secondary to the PN autophagy review. Supporting Evidence: PMID:20643123 regulates both receptor degradation and cytokinesis PMID:25533187 facilitates the lysosomal degradation of epidermal growth factor receptor |
| GO:0005783 endoplasmic reticulum | IDA PMID:24056303 PtdIns(3)P-bound UVRAG coordinates Golgi-ER retrograde and A... | KEEP AS NON CORE | Summary: Endoplasmic reticulum localization is supported for the RINT1/NRZ retrograde trafficking branch. Reason: UVRAG has a PtdIns(3)P-dependent ER tethering and Golgi-ER retrograde transport role. This is supported but secondary to the PN class III PI3K/autophagosome maturation focus. Supporting Evidence: PMID:24056303 PtdIns(3)P)-binding protein PMID:24056303 acts as an integral component of the RINT-1-containing ER tethering complex PMID:24056303 Bif-1-beclin-1-PI(3)KC3 complex to mobilize Atg9 translocation |
| GO:0006890 retrograde vesicle-mediated transport, Golgi to endoplasmic reticulum | IMP PMID:24056303 PtdIns(3)P-bound UVRAG coordinates Golgi-ER retrograde and A... | KEEP AS NON CORE | Summary: Golgi-to-ER retrograde transport is supported for UVRAG and retained as non-core trafficking biology. Reason: UVRAG binds PtdIns(3)P, associates with the RINT1/NRZ ER tethering complex, and coordinates COPI cargo transfer; this is a real trafficking branch outside the core PN autophagosome maturation term. Supporting Evidence: PMID:24056303 PtdIns(3)P)-binding protein PMID:24056303 acts as an integral component of the RINT-1-containing ER tethering complex PMID:24056303 Bif-1-beclin-1-PI(3)KC3 complex to mobilize Atg9 translocation |
| GO:0006914 autophagy | IMP PMID:24056303 PtdIns(3)P-bound UVRAG coordinates Golgi-ER retrograde and A... | MODIFY | Summary: The PMID:24056303 evidence is better captured as ATG9/autophagy-related trafficking rather than broad autophagy. Reason: This paper supports UVRAG movement between ER tethering and Beclin/Bif-1/PI3KC3 machinery to mobilize ATG9 transport; autophagy is too broad for the specific mechanism. Proposed replacements: retrograde vesicle-mediated transport, Golgi to endoplasmic reticulum autophagosome assembly Supporting Evidence: PMID:24056303 PtdIns(3)P)-binding protein PMID:24056303 acts as an integral component of the RINT-1-containing ER tethering complex PMID:24056303 Bif-1-beclin-1-PI(3)KC3 complex to mobilize Atg9 translocation |
| GO:0051684 maintenance of Golgi location | IMP PMID:24056303 PtdIns(3)P-bound UVRAG coordinates Golgi-ER retrograde and A... | KEEP AS NON CORE | Summary: Maintenance of Golgi location is supported through the UVRAG/RINT1 retrograde trafficking branch but non-core. Reason: Knockdown/displacement of UVRAG disrupts COPI cargo transfer and Golgi integrity, but this is secondary to PI3KC3-C2/autophagy maturation in the PN context. Supporting Evidence: PMID:24056303 PtdIns(3)P)-binding protein PMID:24056303 acts as an integral component of the RINT-1-containing ER tethering complex PMID:24056303 Bif-1-beclin-1-PI(3)KC3 complex to mobilize Atg9 translocation |
| GO:0005515 protein binding | IPI PMID:22354037 Genome-wide siRNA screen reveals amino acid starvation-induc... | MARK AS OVER ANNOTATED | Summary: The interaction evidence may be real, but generic protein binding is not an informative UVRAG function. Reason: UVRAG has specific complex/adaptor roles in PI3KC3-C2, HOPS/class C VPS, SNARE, DNA-PK, and other assemblies. Retaining protein binding obscures the biological function and should be replaced by specific complex membership or binding terms where curatable. Supporting Evidence: file:human/UVRAG/UVRAG-uniprot.txt Component of the PI3K (PI3KC3/PI3K-III/class III file:human/UVRAG/UVRAG-uniprot.txt Interacts with VPS16; VPS11; VPS18; VPS33 file:human/UVRAG/UVRAG-uniprot.txt Interacts with PRKDC, XRCC6 and XRCC5 |
| GO:0005515 protein binding | IPI PMID:19270696 Two Beclin 1-binding proteins, Atg14L and Rubicon, reciproca... | MARK AS OVER ANNOTATED | Summary: The interaction evidence may be real, but generic protein binding is not an informative UVRAG function. Reason: UVRAG has specific complex/adaptor roles in PI3KC3-C2, HOPS/class C VPS, SNARE, DNA-PK, and other assemblies. Retaining protein binding obscures the biological function and should be replaced by specific complex membership or binding terms where curatable. Supporting Evidence: file:human/UVRAG/UVRAG-uniprot.txt Component of the PI3K (PI3KC3/PI3K-III/class III file:human/UVRAG/UVRAG-uniprot.txt Interacts with VPS16; VPS11; VPS18; VPS33 file:human/UVRAG/UVRAG-uniprot.txt Interacts with PRKDC, XRCC6 and XRCC5 |
| GO:0005764 lysosome | IDA PMID:19270696 Two Beclin 1-binding proteins, Atg14L and Rubicon, reciproca... | ACCEPT | Summary: Lysosome localization is compatible with UVRAG late autophagy/endolysosomal trafficking. Reason: UVRAG functions in autophagosome fusion with late endosomes/lysosomes and endocytic cargo delivery to degradative compartments. Supporting Evidence: PMID:18552835 autophagosome fusion with late endosomes/lysosomes file:human/UVRAG/UVRAG-uniprot.txt Lysosome {ECO:0000269|PubMed:18843052} |
| GO:0005769 early endosome | IDA PMID:19270696 Two Beclin 1-binding proteins, Atg14L and Rubicon, reciproca... | ACCEPT | Summary: Early endosome localization is supported for UVRAG endosomal trafficking biology. Reason: UVRAG is found on endosomal compartments and contributes to endosome/endosome fusion and degradative endocytic trafficking. Supporting Evidence: PMID:18552835 endosome-endosome fusion, resulting in rapid degradation of endocytic cargo file:human/UVRAG/UVRAG-uniprot.txt Early endosome {ECO:0000269|PubMed:18552835 |
| GO:0005770 late endosome | IDA PMID:19270696 Two Beclin 1-binding proteins, Atg14L and Rubicon, reciproca... | ACCEPT | Summary: Late endosome localization is supported and relevant to UVRAG autophagosome/endosome maturation. Reason: The UVRAG-class C VPS/HOPS axis promotes autophagosome fusion with late endosomes/lysosomes and late endocytic fusion. Supporting Evidence: PMID:18552835 autophagosome fusion with late endosomes/lysosomes file:human/UVRAG/UVRAG-uniprot.txt Late endosome {ECO:0000269|PubMed:18843052} |
| GO:0005737 cytoplasm | TAS PMID:9169138 Molecular cloning of a novel human gene encoding a 63-kDa pr... | KEEP AS NON CORE | Summary: Cytoplasm is a broad legacy localization for UVRAG. Reason: The original cloning paper supports a cytoplasmic protein, but current evidence localizes UVRAG more specifically to endosomes, autophagosomes, ER, midbody, and chromosome/centrosome contexts. Supporting Evidence: PMID:9169138 novel 63-kDa cytoplasmic protein file:human/UVRAG/UVRAG-uniprot.txt Cytoplasmic vesicle, autophagosome |
| GO:0006281 DNA repair | TAS PMID:9169138 Molecular cloning of a novel human gene encoding a 63-kDa pr... | KEEP AS NON CORE | Summary: DNA repair is supported for UVRAG but is an autophagy-independent non-core branch in this PN review. Reason: The strongest evidence supports UVRAG activation of DNA-PK in NHEJ and chromosomal stability, but this should not be treated as the proteostasis/autophagy core function. Supporting Evidence: PMID:9169138 novel 63-kDa cytoplasmic protein PMID:22542840 UVRAG promotes DNA double-strand-break repair by directly binding and activating |
| GO:0030674 protein-macromolecule adaptor activity | IDA PMID:16799551 Autophagic and tumour suppressor activity of a novel Beclin1... | NEW | Summary: UVRAG has a supported adaptor/regulatory subunit role in PI3KC3-C2 and late fusion machinery. Reason: Add this as a more informative molecular-function annotation than generic protein binding. UVRAG links BECN1/PIK3C3 complex machinery with class C VPS/HOPS and SNARE-dependent trafficking during autophagosome/endosome maturation. Supporting Evidence: PMID:16799551 positive regulator of the Beclin1-PI(3)KC3 complex PMID:18843052 Atg14, and UVRAG are not present in the same complex PMID:18552835 interacts with the class C Vps complex PMID:24550300 by assembling a specific fusogenic SNARE complex file:human/UVRAG/UVRAG-uniprot.txt acts as a regulatory subunit of the alternative PI3K complex II |
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Download this section (compressed HTML)Q: Should UVRAG be curated directly to GO:0034272 phosphatidylinositol 3-kinase complex, class III, type II rather than the parent class III PI3K complex term?
Suggested experts: GO autophagy editors, ComplexPortal curators, Reactome autophagy curators
Q: Should UVRAG SNARE/HOPS activity be represented only by SNARE binding and SNARE complex assembly, or is a more specific autophagosome-lysosome fusion adaptor term needed?
Suggested experts: GO molecular function editors, autophagosome maturation experts
Q: Should UVRAG DNA repair and centrosome annotations remain non-core in autophagy-focused reviews even though they are experimentally supported?
Suggested experts: GO DNA repair editors, GO autophagy editors
Experiment: Use UVRAG separation-of-function mutants that disrupt BECN1/PIK3C3 binding, HOPS/class C VPS binding, or SNARE binding, followed by PI3P imaging, STX17/HOPS recruitment, and autophagosome-lysosome fusion assays.
Hypothesis: PI3KC3-C2 complex engagement and HOPS/SNARE engagement define separable UVRAG contributions to PI3P production and autophagosome maturation.
Type: UVRAG autophagy maturation separation-of-function rescue
Experiment: Compare UVRAG wild type, DNA-PK-binding mutants, and CEP63/centrosome-interaction mutants in the same knockout-rescue background with autophagic flux, NHEJ reporter, and centrosome/chromosome segregation readouts.
Hypothesis: UVRAG autophagosome maturation and DNA repair/centrosome functions are genetically separable branches rather than one shared autophagy-dependent phenotype.
Type: parallel autophagy and genome-stability rescue assay
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