id: Q9P2Y5 gene_symbol: UVRAG product_type: PROTEIN status: COMPLETE taxon: id: NCBITaxon:9606 label: Homo sapiens description: '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.' alternative_products: - name: '1' id: Q9P2Y5-1 - name: '2' id: Q9P2Y5-2 sequence_note: VSP_056176 existing_annotations: - term: id: GO:0000323 label: lytic vacuole evidence_type: IBA original_reference_id: GO_REF:0000033 qualifier: is_active_in review: summary: Lytic vacuole is a non-human/generalized ancestor for UVRAG lysosome/endolysosomal localization. action: MODIFY reason: For human UVRAG, lysosome, late endosome, and autophagosome/autophagosome membrane are more precise locations for the late autophagy and endosomal trafficking role. proposed_replacement_terms: - id: GO:0005764 label: lysosome - id: GO:0005770 label: late endosome - id: GO:0005776 label: autophagosome additional_reference_ids: - file:human/UVRAG/UVRAG-uniprot.txt - PMID:18552835 - PMID:18843052 - file:human/UVRAG/UVRAG-notes.md supported_by: - reference_id: file:human/UVRAG/UVRAG-uniprot.txt supporting_text: Late endosome {ECO:0000269|PubMed:18843052} - reference_id: file:human/UVRAG/UVRAG-uniprot.txt supporting_text: Cytoplasmic vesicle, autophagosome - reference_id: file:human/UVRAG/UVRAG-uniprot.txt supporting_text: Early endosome {ECO:0000269|PubMed:18552835 - term: id: GO:0000149 label: SNARE binding evidence_type: IBA original_reference_id: GO_REF:0000033 qualifier: enables review: summary: SNARE binding is supported for UVRAG in late endosomal/autophagosome fusion contexts. action: ACCEPT reason: UVRAG interacts with endosomal SNARE machinery and promotes fusogenic SNARE complex formation with class C VPS/HOPS-associated trafficking machinery. additional_reference_ids: - PMID:24550300 - file:human/UVRAG/UVRAG-uniprot.txt - file:human/UVRAG/UVRAG-notes.md supported_by: - reference_id: PMID:24550300 supporting_text: interactions with the class C vacuolar protein sorting (C-Vps) tethering complex and endosomal - reference_id: PMID:24550300 supporting_text: by assembling a specific fusogenic SNARE complex - reference_id: file:human/UVRAG/UVRAG-uniprot.txt supporting_text: SNARE complex and promotes fusogenic SNARE complex formation during - term: id: GO:0035493 label: SNARE complex assembly evidence_type: IBA original_reference_id: GO_REF:0000033 qualifier: involved_in review: summary: SNARE complex assembly captures a specific UVRAG role in late endosomal/autophagosome fusion machinery. action: ACCEPT reason: UVRAG promotes fusogenic SNARE complex formation in class C VPS/HOPS-dependent membrane fusion, making this more informative than generic protein binding. additional_reference_ids: - PMID:24550300 - file:human/UVRAG/UVRAG-uniprot.txt - file:human/UVRAG/UVRAG-notes.md supported_by: - reference_id: PMID:24550300 supporting_text: interactions with the class C vacuolar protein sorting (C-Vps) tethering complex and endosomal - reference_id: PMID:24550300 supporting_text: by assembling a specific fusogenic SNARE complex - reference_id: file:human/UVRAG/UVRAG-uniprot.txt supporting_text: SNARE complex and promotes fusogenic SNARE complex formation during - term: id: GO:0000775 label: chromosome, centromeric region evidence_type: IEA original_reference_id: GO_REF:0000044 qualifier: located_in review: summary: Centromeric/chromosome localization is experimentally tied to UVRAG genome-stability biology but is not PN core. action: KEEP_AS_NON_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. additional_reference_ids: - PMID:22542840 - file:human/UVRAG/UVRAG-uniprot.txt - file:human/UVRAG/UVRAG-notes.md supported_by: - reference_id: PMID:22542840 supporting_text: UVRAG promotes DNA double-strand-break repair by directly binding and activating - reference_id: PMID:22542840 supporting_text: centrosome instability and aneuploidy - reference_id: file:human/UVRAG/UVRAG-uniprot.txt supporting_text: Promotes DNA double-strand break (DSB) repair by association with DNA-dependent - term: id: GO:0005764 label: lysosome evidence_type: IEA original_reference_id: GO_REF:0000044 qualifier: located_in review: summary: Lysosome localization is compatible with UVRAG late autophagy/endolysosomal trafficking. action: ACCEPT reason: UVRAG functions in autophagosome fusion with late endosomes/lysosomes and endocytic cargo delivery to degradative compartments. additional_reference_ids: - PMID:18552835 - file:human/UVRAG/UVRAG-uniprot.txt - file:human/UVRAG/UVRAG-notes.md supported_by: - reference_id: PMID:18552835 supporting_text: autophagosome fusion with late endosomes/lysosomes - reference_id: file:human/UVRAG/UVRAG-uniprot.txt supporting_text: Lysosome {ECO:0000269|PubMed:18843052} - term: id: GO:0005769 label: early endosome evidence_type: IEA original_reference_id: GO_REF:0000044 qualifier: located_in review: summary: Early endosome localization is supported for UVRAG endosomal trafficking biology. action: ACCEPT reason: UVRAG is found on endosomal compartments and contributes to endosome/endosome fusion and degradative endocytic trafficking. additional_reference_ids: - PMID:18552835 - PMID:18843052 - file:human/UVRAG/UVRAG-uniprot.txt - file:human/UVRAG/UVRAG-notes.md supported_by: - reference_id: PMID:18552835 supporting_text: endosome-endosome fusion, resulting in rapid degradation of endocytic cargo - reference_id: file:human/UVRAG/UVRAG-uniprot.txt supporting_text: Early endosome {ECO:0000269|PubMed:18552835 - term: id: GO:0005770 label: late endosome evidence_type: IEA original_reference_id: GO_REF:0000044 qualifier: located_in review: summary: Late endosome localization is supported and relevant to UVRAG autophagosome/endosome maturation. action: ACCEPT reason: The UVRAG-class C VPS/HOPS axis promotes autophagosome fusion with late endosomes/lysosomes and late endocytic fusion. additional_reference_ids: - PMID:18552835 - PMID:18843052 - file:human/UVRAG/UVRAG-uniprot.txt - file:human/UVRAG/UVRAG-notes.md supported_by: - reference_id: PMID:18552835 supporting_text: autophagosome fusion with late endosomes/lysosomes - reference_id: file:human/UVRAG/UVRAG-uniprot.txt supporting_text: Late endosome {ECO:0000269|PubMed:18843052} - term: id: GO:0005776 label: autophagosome evidence_type: IEA original_reference_id: GO_REF:0000044 qualifier: located_in review: summary: Autophagosome localization is directly relevant to UVRAG/PACER-mediated autophagosome maturation. action: ACCEPT reason: UVRAG is recruited to autophagosome-associated structures and participates in PI3KC3/HOPS activation during autophagosome maturation. additional_reference_ids: - PMID:28306502 - file:human/UVRAG/UVRAG-uniprot.txt - file:human/UVRAG/UVRAG-notes.md supported_by: - reference_id: PMID:28306502 supporting_text: Pacer recruits PI3KC3 and HOPS complexes to the autophagosome - reference_id: file:human/UVRAG/UVRAG-uniprot.txt supporting_text: Cytoplasmic vesicle, autophagosome - term: id: GO:0005783 label: endoplasmic reticulum evidence_type: IEA original_reference_id: GO_REF:0000044 qualifier: located_in review: summary: Endoplasmic reticulum localization is supported for the RINT1/NRZ retrograde trafficking branch. action: KEEP_AS_NON_CORE 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. additional_reference_ids: - PMID:24056303 - file:human/UVRAG/UVRAG-uniprot.txt - file:human/UVRAG/UVRAG-notes.md supported_by: - reference_id: PMID:24056303 supporting_text: PtdIns(3)P)-binding protein - reference_id: PMID:24056303 supporting_text: acts as an integral component of the RINT-1-containing ER tethering complex - reference_id: PMID:24056303 supporting_text: Bif-1-beclin-1-PI(3)KC3 complex to mobilize Atg9 translocation - term: id: GO:0006914 label: autophagy evidence_type: IEA original_reference_id: GO_REF:0000117 qualifier: involved_in review: summary: Broad autophagy is directionally correct but should be narrowed to UVRAG autophagosome maturation/positive autophagy regulation. action: MODIFY reason: UVRAG regulates class III PI3K/HOPS-dependent autophagosome maturation and Beclin1-PI3KC3 autophagy signaling; the parent autophagy term loses that specificity. proposed_replacement_terms: - id: GO:0097352 label: autophagosome maturation - id: GO:0010508 label: positive regulation of autophagy additional_reference_ids: - PMID:16799551 - PMID:18552835 - PMID:28306502 - file:human/UVRAG/UVRAG-uniprot.txt - file:human/UVRAG/UVRAG-notes.md supported_by: - reference_id: PMID:16799551 supporting_text: positive regulator of the Beclin1-PI(3)KC3 complex - reference_id: PMID:18843052 supporting_text: Atg14, and UVRAG are not present in the same complex - reference_id: file:human/UVRAG/UVRAG-uniprot.txt supporting_text: acts as a regulatory subunit of the alternative PI3K complex II - reference_id: file:human/UVRAG/UVRAG-uniprot.txt supporting_text: mediates formation of phosphatidylinositol 3-phosphate - reference_id: PMID:18552835 supporting_text: interacts with the class C Vps complex - reference_id: PMID:18552835 supporting_text: autophagosome fusion with late endosomes/lysosomes - term: id: GO:0016192 label: vesicle-mediated transport evidence_type: IEA original_reference_id: GO_REF:0000117 qualifier: involved_in review: summary: Vesicle-mediated transport is too broad for UVRAG; the supported processes are Golgi-ER retrograde transport and endolysosomal/autophagic trafficking. action: MODIFY 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_replacement_terms: - id: GO:0006890 label: retrograde vesicle-mediated transport, Golgi to endoplasmic reticulum - id: GO:0071985 label: multivesicular body sorting pathway - id: GO:0097352 label: autophagosome maturation additional_reference_ids: - PMID:18552835 - PMID:24056303 - file:human/UVRAG/UVRAG-uniprot.txt - file:human/UVRAG/UVRAG-notes.md supported_by: - reference_id: PMID:18552835 supporting_text: interacts with the class C Vps complex - reference_id: PMID:18552835 supporting_text: autophagosome fusion with late endosomes/lysosomes - reference_id: PMID:24056303 supporting_text: PtdIns(3)P)-binding protein - reference_id: PMID:24056303 supporting_text: acts as an integral component of the RINT-1-containing ER tethering complex - reference_id: PMID:24056303 supporting_text: Bif-1-beclin-1-PI(3)KC3 complex to mobilize Atg9 translocation - term: id: GO:0030496 label: midbody evidence_type: IEA original_reference_id: GO_REF:0000044 qualifier: located_in review: summary: Midbody localization is supported for UVRAG cytokinesis biology but is not PN core. action: KEEP_AS_NON_CORE reason: The PI3KC3-C2/BIF-1-containing subcomplex has a supported cytokinesis/midbody branch; retain it as non-core relative to autophagosome maturation. additional_reference_ids: - PMID:20643123 - file:human/UVRAG/UVRAG-uniprot.txt - file:human/UVRAG/UVRAG-notes.md supported_by: - reference_id: PMID:20643123 supporting_text: strong localisation of these proteins to the midbody - reference_id: file:human/UVRAG/UVRAG-uniprot.txt supporting_text: Midbody - term: id: GO:0031410 label: cytoplasmic vesicle evidence_type: IEA original_reference_id: GO_REF:0000117 qualifier: located_in review: summary: Cytoplasmic vesicle is true but too broad for UVRAG localization. action: MODIFY reason: UVRAG is better localized to autophagosome/autophagosome membrane and early/late endosome compartments relevant to PI3KC3-C2 and HOPS/SNARE trafficking. proposed_replacement_terms: - id: GO:0005776 label: autophagosome - id: GO:0000421 label: autophagosome membrane - id: GO:0005769 label: early endosome - id: GO:0005770 label: late endosome additional_reference_ids: - PMID:18552835 - PMID:28306502 - file:human/UVRAG/UVRAG-uniprot.txt - file:human/UVRAG/UVRAG-notes.md supported_by: - reference_id: file:human/UVRAG/UVRAG-uniprot.txt supporting_text: Late endosome {ECO:0000269|PubMed:18843052} - reference_id: file:human/UVRAG/UVRAG-uniprot.txt supporting_text: Cytoplasmic vesicle, autophagosome - reference_id: file:human/UVRAG/UVRAG-uniprot.txt supporting_text: Early endosome {ECO:0000269|PubMed:18552835 - term: id: GO:0036092 label: phosphatidylinositol-3-phosphate biosynthetic process evidence_type: IEA original_reference_id: GO_REF:0000117 qualifier: involved_in review: summary: UVRAG is involved in PI3P biosynthesis as a PI3KC3-C2 regulatory subunit rather than as the lipid kinase itself. action: ACCEPT reason: UVRAG activates/regulates PIK3C3/VPS34 within PI3KC3-C2, which mediates formation of phosphatidylinositol 3-phosphate during autophagy/endosomal trafficking. additional_reference_ids: - PMID:16799551 - PMID:20643123 - PMID:24056303 - file:human/UVRAG/UVRAG-uniprot.txt - file:human/UVRAG/UVRAG-notes.md supported_by: - reference_id: PMID:16799551 supporting_text: positive regulator of the Beclin1-PI(3)KC3 complex - reference_id: PMID:18843052 supporting_text: Atg14, and UVRAG are not present in the same complex - reference_id: file:human/UVRAG/UVRAG-uniprot.txt supporting_text: acts as a regulatory subunit of the alternative PI3K complex II - reference_id: file:human/UVRAG/UVRAG-uniprot.txt supporting_text: mediates formation of phosphatidylinositol 3-phosphate - term: id: GO:0043933 label: protein-containing complex organization evidence_type: IEA original_reference_id: GO_REF:0000117 qualifier: involved_in review: summary: Protein-containing complex organization is too broad for UVRAG; SNARE/HOPS and PI3KC3-C2 complex roles are more specific. action: MODIFY 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_replacement_terms: - id: GO:0035493 label: SNARE complex assembly - id: GO:0034272 label: phosphatidylinositol 3-kinase complex, class III, type II additional_reference_ids: - PMID:24550300 - file:human/UVRAG/UVRAG-uniprot.txt - file:human/UVRAG/UVRAG-notes.md supported_by: - reference_id: PMID:24550300 supporting_text: interactions with the class C vacuolar protein sorting (C-Vps) tethering complex and endosomal - reference_id: PMID:24550300 supporting_text: by assembling a specific fusogenic SNARE complex - reference_id: file:human/UVRAG/UVRAG-uniprot.txt supporting_text: SNARE complex and promotes fusogenic SNARE complex formation during - reference_id: PMID:16799551 supporting_text: positive regulator of the Beclin1-PI(3)KC3 complex - reference_id: PMID:18843052 supporting_text: Atg14, and UVRAG are not present in the same complex - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:17891140 qualifier: enables review: summary: The interaction evidence may be real, but generic protein binding is not an informative UVRAG function. action: MARK_AS_OVER_ANNOTATED 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. additional_reference_ids: - file:human/UVRAG/UVRAG-uniprot.txt - file:human/UVRAG/UVRAG-notes.md supported_by: - reference_id: file:human/UVRAG/UVRAG-uniprot.txt supporting_text: Component of the PI3K (PI3KC3/PI3K-III/class III - reference_id: file:human/UVRAG/UVRAG-uniprot.txt supporting_text: Interacts with VPS16; VPS11; VPS18; VPS33 - reference_id: file:human/UVRAG/UVRAG-uniprot.txt supporting_text: Interacts with PRKDC, XRCC6 and XRCC5 - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:19050071 qualifier: enables review: summary: The interaction evidence may be real, but generic protein binding is not an informative UVRAG function. action: MARK_AS_OVER_ANNOTATED 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. additional_reference_ids: - file:human/UVRAG/UVRAG-uniprot.txt - file:human/UVRAG/UVRAG-notes.md supported_by: - reference_id: file:human/UVRAG/UVRAG-uniprot.txt supporting_text: Component of the PI3K (PI3KC3/PI3K-III/class III - reference_id: file:human/UVRAG/UVRAG-uniprot.txt supporting_text: Interacts with VPS16; VPS11; VPS18; VPS33 - reference_id: file:human/UVRAG/UVRAG-uniprot.txt supporting_text: Interacts with PRKDC, XRCC6 and XRCC5 - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:20562859 qualifier: enables review: summary: The interaction evidence may be real, but generic protein binding is not an informative UVRAG function. action: MARK_AS_OVER_ANNOTATED 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. additional_reference_ids: - file:human/UVRAG/UVRAG-uniprot.txt - file:human/UVRAG/UVRAG-notes.md supported_by: - reference_id: file:human/UVRAG/UVRAG-uniprot.txt supporting_text: Component of the PI3K (PI3KC3/PI3K-III/class III - reference_id: file:human/UVRAG/UVRAG-uniprot.txt supporting_text: Interacts with VPS16; VPS11; VPS18; VPS33 - reference_id: file:human/UVRAG/UVRAG-uniprot.txt supporting_text: Interacts with PRKDC, XRCC6 and XRCC5 - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:21062745 qualifier: enables review: summary: The interaction evidence may be real, but generic protein binding is not an informative UVRAG function. action: MARK_AS_OVER_ANNOTATED 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. additional_reference_ids: - file:human/UVRAG/UVRAG-uniprot.txt - file:human/UVRAG/UVRAG-notes.md supported_by: - reference_id: file:human/UVRAG/UVRAG-uniprot.txt supporting_text: Component of the PI3K (PI3KC3/PI3K-III/class III - reference_id: file:human/UVRAG/UVRAG-uniprot.txt supporting_text: Interacts with VPS16; VPS11; VPS18; VPS33 - reference_id: file:human/UVRAG/UVRAG-uniprot.txt supporting_text: Interacts with PRKDC, XRCC6 and XRCC5 - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:21597469 qualifier: enables review: summary: The interaction evidence may be real, but generic protein binding is not an informative UVRAG function. action: MARK_AS_OVER_ANNOTATED 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. additional_reference_ids: - file:human/UVRAG/UVRAG-uniprot.txt - file:human/UVRAG/UVRAG-notes.md supported_by: - reference_id: file:human/UVRAG/UVRAG-uniprot.txt supporting_text: Component of the PI3K (PI3KC3/PI3K-III/class III - reference_id: file:human/UVRAG/UVRAG-uniprot.txt supporting_text: Interacts with VPS16; VPS11; VPS18; VPS33 - reference_id: file:human/UVRAG/UVRAG-uniprot.txt supporting_text: Interacts with PRKDC, XRCC6 and XRCC5 - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:22081109 qualifier: enables review: summary: The interaction evidence may be real, but generic protein binding is not an informative UVRAG function. action: MARK_AS_OVER_ANNOTATED 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. additional_reference_ids: - file:human/UVRAG/UVRAG-uniprot.txt - file:human/UVRAG/UVRAG-notes.md supported_by: - reference_id: file:human/UVRAG/UVRAG-uniprot.txt supporting_text: Component of the PI3K (PI3KC3/PI3K-III/class III - reference_id: file:human/UVRAG/UVRAG-uniprot.txt supporting_text: Interacts with VPS16; VPS11; VPS18; VPS33 - reference_id: file:human/UVRAG/UVRAG-uniprot.txt supporting_text: Interacts with PRKDC, XRCC6 and XRCC5 - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:22493499 qualifier: enables review: summary: The interaction evidence may be real, but generic protein binding is not an informative UVRAG function. action: MARK_AS_OVER_ANNOTATED 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. additional_reference_ids: - file:human/UVRAG/UVRAG-uniprot.txt - file:human/UVRAG/UVRAG-notes.md supported_by: - reference_id: file:human/UVRAG/UVRAG-uniprot.txt supporting_text: Component of the PI3K (PI3KC3/PI3K-III/class III - reference_id: file:human/UVRAG/UVRAG-uniprot.txt supporting_text: Interacts with VPS16; VPS11; VPS18; VPS33 - reference_id: file:human/UVRAG/UVRAG-uniprot.txt supporting_text: Interacts with PRKDC, XRCC6 and XRCC5 - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:23954414 qualifier: enables review: summary: The interaction evidence may be real, but generic protein binding is not an informative UVRAG function. action: MARK_AS_OVER_ANNOTATED 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. additional_reference_ids: - file:human/UVRAG/UVRAG-uniprot.txt - file:human/UVRAG/UVRAG-notes.md supported_by: - reference_id: file:human/UVRAG/UVRAG-uniprot.txt supporting_text: Component of the PI3K (PI3KC3/PI3K-III/class III - reference_id: file:human/UVRAG/UVRAG-uniprot.txt supporting_text: Interacts with VPS16; VPS11; VPS18; VPS33 - reference_id: file:human/UVRAG/UVRAG-uniprot.txt supporting_text: Interacts with PRKDC, XRCC6 and XRCC5 - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:24034250 qualifier: enables review: summary: The interaction evidence may be real, but generic protein binding is not an informative UVRAG function. action: MARK_AS_OVER_ANNOTATED 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. additional_reference_ids: - file:human/UVRAG/UVRAG-uniprot.txt - file:human/UVRAG/UVRAG-notes.md supported_by: - reference_id: file:human/UVRAG/UVRAG-uniprot.txt supporting_text: Component of the PI3K (PI3KC3/PI3K-III/class III - reference_id: file:human/UVRAG/UVRAG-uniprot.txt supporting_text: Interacts with VPS16; VPS11; VPS18; VPS33 - reference_id: file:human/UVRAG/UVRAG-uniprot.txt supporting_text: Interacts with PRKDC, XRCC6 and XRCC5 - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:24056303 qualifier: enables review: summary: The interaction evidence may be real, but generic protein binding is not an informative UVRAG function. action: MARK_AS_OVER_ANNOTATED 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. additional_reference_ids: - file:human/UVRAG/UVRAG-uniprot.txt - file:human/UVRAG/UVRAG-notes.md supported_by: - reference_id: file:human/UVRAG/UVRAG-uniprot.txt supporting_text: Component of the PI3K (PI3KC3/PI3K-III/class III - reference_id: file:human/UVRAG/UVRAG-uniprot.txt supporting_text: Interacts with VPS16; VPS11; VPS18; VPS33 - reference_id: file:human/UVRAG/UVRAG-uniprot.txt supporting_text: Interacts with PRKDC, XRCC6 and XRCC5 - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:24554770 qualifier: enables review: summary: The interaction evidence may be real, but generic protein binding is not an informative UVRAG function. action: MARK_AS_OVER_ANNOTATED 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. additional_reference_ids: - file:human/UVRAG/UVRAG-uniprot.txt - file:human/UVRAG/UVRAG-notes.md supported_by: - reference_id: file:human/UVRAG/UVRAG-uniprot.txt supporting_text: Component of the PI3K (PI3KC3/PI3K-III/class III - reference_id: file:human/UVRAG/UVRAG-uniprot.txt supporting_text: Interacts with VPS16; VPS11; VPS18; VPS33 - reference_id: file:human/UVRAG/UVRAG-uniprot.txt supporting_text: Interacts with PRKDC, XRCC6 and XRCC5 - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:24785657 qualifier: enables review: summary: The interaction evidence may be real, but generic protein binding is not an informative UVRAG function. action: MARK_AS_OVER_ANNOTATED 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. additional_reference_ids: - file:human/UVRAG/UVRAG-uniprot.txt - file:human/UVRAG/UVRAG-notes.md supported_by: - reference_id: file:human/UVRAG/UVRAG-uniprot.txt supporting_text: Component of the PI3K (PI3KC3/PI3K-III/class III - reference_id: file:human/UVRAG/UVRAG-uniprot.txt supporting_text: Interacts with VPS16; VPS11; VPS18; VPS33 - reference_id: file:human/UVRAG/UVRAG-uniprot.txt supporting_text: Interacts with PRKDC, XRCC6 and XRCC5 - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:24849286 qualifier: enables review: summary: The interaction evidence may be real, but generic protein binding is not an informative UVRAG function. action: MARK_AS_OVER_ANNOTATED 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. additional_reference_ids: - file:human/UVRAG/UVRAG-uniprot.txt - file:human/UVRAG/UVRAG-notes.md supported_by: - reference_id: file:human/UVRAG/UVRAG-uniprot.txt supporting_text: Component of the PI3K (PI3KC3/PI3K-III/class III - reference_id: file:human/UVRAG/UVRAG-uniprot.txt supporting_text: Interacts with VPS16; VPS11; VPS18; VPS33 - reference_id: file:human/UVRAG/UVRAG-uniprot.txt supporting_text: Interacts with PRKDC, XRCC6 and XRCC5 - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:25490155 qualifier: enables review: summary: The interaction evidence may be real, but generic protein binding is not an informative UVRAG function. action: MARK_AS_OVER_ANNOTATED 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. additional_reference_ids: - file:human/UVRAG/UVRAG-uniprot.txt - file:human/UVRAG/UVRAG-notes.md supported_by: - reference_id: file:human/UVRAG/UVRAG-uniprot.txt supporting_text: Component of the PI3K (PI3KC3/PI3K-III/class III - reference_id: file:human/UVRAG/UVRAG-uniprot.txt supporting_text: Interacts with VPS16; VPS11; VPS18; VPS33 - reference_id: file:human/UVRAG/UVRAG-uniprot.txt supporting_text: Interacts with PRKDC, XRCC6 and XRCC5 - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:26496610 qualifier: enables review: summary: The interaction evidence may be real, but generic protein binding is not an informative UVRAG function. action: MARK_AS_OVER_ANNOTATED 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. additional_reference_ids: - file:human/UVRAG/UVRAG-uniprot.txt - file:human/UVRAG/UVRAG-notes.md supported_by: - reference_id: file:human/UVRAG/UVRAG-uniprot.txt supporting_text: Component of the PI3K (PI3KC3/PI3K-III/class III - reference_id: file:human/UVRAG/UVRAG-uniprot.txt supporting_text: Interacts with VPS16; VPS11; VPS18; VPS33 - reference_id: file:human/UVRAG/UVRAG-uniprot.txt supporting_text: Interacts with PRKDC, XRCC6 and XRCC5 - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:32296183 qualifier: enables review: summary: The interaction evidence may be real, but generic protein binding is not an informative UVRAG function. action: MARK_AS_OVER_ANNOTATED 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. additional_reference_ids: - file:human/UVRAG/UVRAG-uniprot.txt - file:human/UVRAG/UVRAG-notes.md supported_by: - reference_id: file:human/UVRAG/UVRAG-uniprot.txt supporting_text: Component of the PI3K (PI3KC3/PI3K-III/class III - reference_id: file:human/UVRAG/UVRAG-uniprot.txt supporting_text: Interacts with VPS16; VPS11; VPS18; VPS33 - reference_id: file:human/UVRAG/UVRAG-uniprot.txt supporting_text: Interacts with PRKDC, XRCC6 and XRCC5 - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:33961781 qualifier: enables review: summary: The interaction evidence may be real, but generic protein binding is not an informative UVRAG function. action: MARK_AS_OVER_ANNOTATED 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. additional_reference_ids: - file:human/UVRAG/UVRAG-uniprot.txt - file:human/UVRAG/UVRAG-notes.md supported_by: - reference_id: file:human/UVRAG/UVRAG-uniprot.txt supporting_text: Component of the PI3K (PI3KC3/PI3K-III/class III - reference_id: file:human/UVRAG/UVRAG-uniprot.txt supporting_text: Interacts with VPS16; VPS11; VPS18; VPS33 - reference_id: file:human/UVRAG/UVRAG-uniprot.txt supporting_text: Interacts with PRKDC, XRCC6 and XRCC5 - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:34386498 qualifier: enables review: summary: The interaction evidence may be real, but generic protein binding is not an informative UVRAG function. action: MARK_AS_OVER_ANNOTATED 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. additional_reference_ids: - file:human/UVRAG/UVRAG-uniprot.txt - file:human/UVRAG/UVRAG-notes.md supported_by: - reference_id: file:human/UVRAG/UVRAG-uniprot.txt supporting_text: Component of the PI3K (PI3KC3/PI3K-III/class III - reference_id: file:human/UVRAG/UVRAG-uniprot.txt supporting_text: Interacts with VPS16; VPS11; VPS18; VPS33 - reference_id: file:human/UVRAG/UVRAG-uniprot.txt supporting_text: Interacts with PRKDC, XRCC6 and XRCC5 - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:35044719 qualifier: enables review: summary: The interaction evidence may be real, but generic protein binding is not an informative UVRAG function. action: MARK_AS_OVER_ANNOTATED 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. additional_reference_ids: - file:human/UVRAG/UVRAG-uniprot.txt - file:human/UVRAG/UVRAG-notes.md supported_by: - reference_id: file:human/UVRAG/UVRAG-uniprot.txt supporting_text: Component of the PI3K (PI3KC3/PI3K-III/class III - reference_id: file:human/UVRAG/UVRAG-uniprot.txt supporting_text: Interacts with VPS16; VPS11; VPS18; VPS33 - reference_id: file:human/UVRAG/UVRAG-uniprot.txt supporting_text: Interacts with PRKDC, XRCC6 and XRCC5 - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:35271311 qualifier: enables review: summary: The interaction evidence may be real, but generic protein binding is not an informative UVRAG function. action: MARK_AS_OVER_ANNOTATED 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. additional_reference_ids: - file:human/UVRAG/UVRAG-uniprot.txt - file:human/UVRAG/UVRAG-notes.md supported_by: - reference_id: file:human/UVRAG/UVRAG-uniprot.txt supporting_text: Component of the PI3K (PI3KC3/PI3K-III/class III - reference_id: file:human/UVRAG/UVRAG-uniprot.txt supporting_text: Interacts with VPS16; VPS11; VPS18; VPS33 - reference_id: file:human/UVRAG/UVRAG-uniprot.txt supporting_text: Interacts with PRKDC, XRCC6 and XRCC5 - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:37219487 qualifier: enables review: summary: The interaction evidence may be real, but generic protein binding is not an informative UVRAG function. action: MARK_AS_OVER_ANNOTATED 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. additional_reference_ids: - file:human/UVRAG/UVRAG-uniprot.txt - file:human/UVRAG/UVRAG-notes.md supported_by: - reference_id: file:human/UVRAG/UVRAG-uniprot.txt supporting_text: Component of the PI3K (PI3KC3/PI3K-III/class III - reference_id: file:human/UVRAG/UVRAG-uniprot.txt supporting_text: Interacts with VPS16; VPS11; VPS18; VPS33 - reference_id: file:human/UVRAG/UVRAG-uniprot.txt supporting_text: Interacts with PRKDC, XRCC6 and XRCC5 - term: id: GO:0000149 label: SNARE binding evidence_type: IEA original_reference_id: GO_REF:0000107 qualifier: enables review: summary: SNARE binding is supported for UVRAG in late endosomal/autophagosome fusion contexts. action: ACCEPT reason: UVRAG interacts with endosomal SNARE machinery and promotes fusogenic SNARE complex formation with class C VPS/HOPS-associated trafficking machinery. additional_reference_ids: - PMID:24550300 - file:human/UVRAG/UVRAG-uniprot.txt - file:human/UVRAG/UVRAG-notes.md supported_by: - reference_id: PMID:24550300 supporting_text: interactions with the class C vacuolar protein sorting (C-Vps) tethering complex and endosomal - reference_id: PMID:24550300 supporting_text: by assembling a specific fusogenic SNARE complex - reference_id: file:human/UVRAG/UVRAG-uniprot.txt supporting_text: SNARE complex and promotes fusogenic SNARE complex formation during - term: id: GO:0006281 label: DNA repair evidence_type: IEA original_reference_id: GO_REF:0000120 qualifier: involved_in review: summary: DNA repair is supported for UVRAG but is an autophagy-independent non-core branch in this PN review. action: KEEP_AS_NON_CORE 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. additional_reference_ids: - PMID:22542840 - file:human/UVRAG/UVRAG-uniprot.txt - file:human/UVRAG/UVRAG-notes.md supported_by: - reference_id: PMID:22542840 supporting_text: UVRAG promotes DNA double-strand-break repair by directly binding and activating - reference_id: PMID:22542840 supporting_text: centrosome instability and aneuploidy - reference_id: file:human/UVRAG/UVRAG-uniprot.txt supporting_text: Promotes DNA double-strand break (DSB) repair by association with DNA-dependent - term: id: GO:0007051 label: spindle organization evidence_type: IEA original_reference_id: GO_REF:0000107 qualifier: involved_in review: summary: Spindle organization is a non-core inference from UVRAG centrosome/chromosome stability biology. action: KEEP_AS_NON_CORE reason: The paper supports proper chromosome segregation and centrosome stability, but this is outside the class III PI3K/autophagosome maturation core. additional_reference_ids: - PMID:22542840 - file:human/UVRAG/UVRAG-uniprot.txt - file:human/UVRAG/UVRAG-notes.md supported_by: - reference_id: PMID:22542840 supporting_text: UVRAG promotes DNA double-strand-break repair by directly binding and activating - reference_id: PMID:22542840 supporting_text: centrosome instability and aneuploidy - reference_id: file:human/UVRAG/UVRAG-uniprot.txt supporting_text: Promotes DNA double-strand break (DSB) repair by association with DNA-dependent - term: id: GO:0007059 label: chromosome segregation evidence_type: IEA original_reference_id: GO_REF:0000107 qualifier: involved_in review: summary: Chromosome segregation is supported by UVRAG centrosome/chromosome stability evidence but is non-core. action: KEEP_AS_NON_CORE reason: UVRAG disruption causes centrosome instability and aneuploidy; retain as non-core genome-stability biology. additional_reference_ids: - PMID:22542840 - file:human/UVRAG/UVRAG-uniprot.txt - file:human/UVRAG/UVRAG-notes.md supported_by: - reference_id: PMID:22542840 supporting_text: UVRAG promotes DNA double-strand-break repair by directly binding and activating - reference_id: PMID:22542840 supporting_text: centrosome instability and aneuploidy - reference_id: file:human/UVRAG/UVRAG-uniprot.txt supporting_text: Promotes DNA double-strand break (DSB) repair by association with DNA-dependent - term: id: GO:0007098 label: centrosome cycle evidence_type: IEA original_reference_id: GO_REF:0000120 qualifier: involved_in review: summary: Centrosome cycle is supported as a non-core centrosome stability/chromosome segregation branch. action: KEEP_AS_NON_CORE reason: UVRAG interacts with CEP63 and is required for centrosome stability, but this is separate from the PN autophagy/endolysosomal core. additional_reference_ids: - PMID:22542840 - file:human/UVRAG/UVRAG-uniprot.txt - file:human/UVRAG/UVRAG-notes.md supported_by: - reference_id: PMID:22542840 supporting_text: UVRAG promotes DNA double-strand-break repair by directly binding and activating - reference_id: PMID:22542840 supporting_text: centrosome instability and aneuploidy - reference_id: file:human/UVRAG/UVRAG-uniprot.txt supporting_text: Promotes DNA double-strand break (DSB) repair by association with DNA-dependent - term: id: GO:0017124 label: SH3 domain binding evidence_type: IEA original_reference_id: GO_REF:0000107 qualifier: enables review: summary: SH3 domain binding is compatible with the SH3GLB1/Bif-1 interaction but is not the core UVRAG function. action: KEEP_AS_NON_CORE 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. additional_reference_ids: - PMID:17891140 - file:human/UVRAG/UVRAG-uniprot.txt - file:human/UVRAG/UVRAG-notes.md supported_by: - reference_id: PMID:17891140 supporting_text: Bif-1 interacts with Beclin 1 through UVRAG - reference_id: file:human/UVRAG/UVRAG-uniprot.txt supporting_text: Interacts with SH3GLB1 - term: id: GO:0032991 label: protein-containing complex evidence_type: IEA original_reference_id: GO_REF:0000120 qualifier: part_of review: summary: Protein-containing complex is correct but too generic for UVRAG. action: MODIFY 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_replacement_terms: - id: GO:0034272 label: phosphatidylinositol 3-kinase complex, class III, type II additional_reference_ids: - PMID:18843052 - PMID:20643123 - file:human/UVRAG/UVRAG-uniprot.txt - file:human/UVRAG/UVRAG-notes.md supported_by: - reference_id: PMID:16799551 supporting_text: positive regulator of the Beclin1-PI(3)KC3 complex - reference_id: PMID:18843052 supporting_text: Atg14, and UVRAG are not present in the same complex - reference_id: file:human/UVRAG/UVRAG-uniprot.txt supporting_text: acts as a regulatory subunit of the alternative PI3K complex II - reference_id: file:human/UVRAG/UVRAG-uniprot.txt supporting_text: mediates formation of phosphatidylinositol 3-phosphate - term: id: GO:0045335 label: phagocytic vesicle evidence_type: IEA original_reference_id: GO_REF:0000107 qualifier: located_in review: summary: Phagocytic vesicle context is supported through SLAMF1/Vps34/Beclin1/UVRAG phagosome signaling but is non-core. action: KEEP_AS_NON_CORE reason: This is a macrophage/phagosome-specific branch of UVRAG-containing class III PI3K signaling rather than the central autophagosome maturation role. additional_reference_ids: - PMID:22493499 - file:human/UVRAG/UVRAG-uniprot.txt - file:human/UVRAG/UVRAG-notes.md supported_by: - reference_id: PMID:22493499 supporting_text: Slamf1 interacts with the class III PI3K Vps34 in a complex with Beclin-1 and UVRAG - reference_id: PMID:22493499 supporting_text: Slamf1 recruits a subset of Vps34-associated proteins - term: id: GO:0010506 label: regulation of autophagy evidence_type: IDA original_reference_id: PMID:16799551 qualifier: involved_in review: summary: UVRAG positively regulates Beclin1-PI3KC3 autophagy activity, so the undirected regulation term should be narrowed. action: MODIFY reason: The cited evidence presents UVRAG as a positive regulator/activator of the Beclin1-PI3KC3 complex and autophagy, not merely an unspecified regulator. proposed_replacement_terms: - id: GO:0010508 label: positive regulation of autophagy - id: GO:0097352 label: autophagosome maturation additional_reference_ids: - PMID:16799551 - PMID:18552835 - file:human/UVRAG/UVRAG-uniprot.txt - file:human/UVRAG/UVRAG-notes.md supported_by: - reference_id: PMID:16799551 supporting_text: positive regulator of the Beclin1-PI(3)KC3 complex - reference_id: PMID:16799551 supporting_text: UVRAG-mediated activation of the Beclin1-PI(3)KC3 complex promotes autophagy - term: id: GO:0035032 label: phosphatidylinositol 3-kinase complex, class III evidence_type: IPI original_reference_id: PMID:25490155 qualifier: part_of review: summary: Generic class III PI3K complex membership is correct but underspecified for UVRAG. action: MODIFY 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_replacement_terms: - id: GO:0034272 label: phosphatidylinositol 3-kinase complex, class III, type II additional_reference_ids: - PMID:18843052 - PMID:20643123 - file:human/UVRAG/UVRAG-uniprot.txt - file:human/UVRAG/UVRAG-notes.md supported_by: - reference_id: PMID:16799551 supporting_text: positive regulator of the Beclin1-PI(3)KC3 complex - reference_id: PMID:18843052 supporting_text: Atg14, and UVRAG are not present in the same complex - reference_id: file:human/UVRAG/UVRAG-uniprot.txt supporting_text: acts as a regulatory subunit of the alternative PI3K complex II - reference_id: file:human/UVRAG/UVRAG-uniprot.txt supporting_text: mediates formation of phosphatidylinositol 3-phosphate - term: id: GO:0036092 label: phosphatidylinositol-3-phosphate biosynthetic process evidence_type: IDA original_reference_id: PMID:8999962 qualifier: involved_in review: summary: UVRAG is involved in PI3P biosynthesis as a PI3KC3-C2 regulatory subunit rather than as the lipid kinase itself. action: ACCEPT reason: UVRAG activates/regulates PIK3C3/VPS34 within PI3KC3-C2, which mediates formation of phosphatidylinositol 3-phosphate during autophagy/endosomal trafficking. additional_reference_ids: - PMID:16799551 - PMID:20643123 - PMID:24056303 - file:human/UVRAG/UVRAG-uniprot.txt - file:human/UVRAG/UVRAG-notes.md supported_by: - reference_id: PMID:16799551 supporting_text: positive regulator of the Beclin1-PI(3)KC3 complex - reference_id: PMID:18843052 supporting_text: Atg14, and UVRAG are not present in the same complex - reference_id: file:human/UVRAG/UVRAG-uniprot.txt supporting_text: acts as a regulatory subunit of the alternative PI3K complex II - reference_id: file:human/UVRAG/UVRAG-uniprot.txt supporting_text: mediates formation of phosphatidylinositol 3-phosphate - term: id: GO:0005769 label: early endosome evidence_type: EXP original_reference_id: PMID:18552835 qualifier: located_in review: summary: Early endosome localization is supported for UVRAG endosomal trafficking biology. action: ACCEPT reason: UVRAG is found on endosomal compartments and contributes to endosome/endosome fusion and degradative endocytic trafficking. additional_reference_ids: - PMID:18552835 - PMID:18843052 - file:human/UVRAG/UVRAG-uniprot.txt - file:human/UVRAG/UVRAG-notes.md supported_by: - reference_id: PMID:18552835 supporting_text: endosome-endosome fusion, resulting in rapid degradation of endocytic cargo - reference_id: file:human/UVRAG/UVRAG-uniprot.txt supporting_text: Early endosome {ECO:0000269|PubMed:18552835 - term: id: GO:0033116 label: endoplasmic reticulum-Golgi intermediate compartment membrane evidence_type: TAS original_reference_id: Reactome:R-HSA-9730505 qualifier: located_in review: summary: ERGIC membrane is a virus-event-specific Reactome localization and is too specific for general UVRAG biology. action: MARK_AS_OVER_ANNOTATED 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. proposed_replacement_terms: - id: GO:0005783 label: endoplasmic reticulum - id: GO:0005776 label: autophagosome - id: GO:0005769 label: early endosome additional_reference_ids: - Reactome:R-HSA-9730505 - file:human/UVRAG/UVRAG-uniprot.txt - file:human/UVRAG/UVRAG-notes.md supported_by: - reference_id: Reactome:R-HSA-9730505 supporting_text: SARS-CoV-2 3a binds to UVRAG - reference_id: file:human/UVRAG/UVRAG-uniprot.txt supporting_text: Endoplasmic reticulum {ECO:0000269|PubMed:24056303} - term: id: GO:0000421 label: autophagosome membrane evidence_type: IDA original_reference_id: PMID:28306502 qualifier: located_in review: summary: Autophagosome membrane localization is directly supported for UVRAG/PACER-mediated maturation. action: ACCEPT reason: UVRAG is recruited to autophagosomes through RUBCNL/PACER and supports local PI3KC3/HOPS activity for autophagosome maturation. additional_reference_ids: - PMID:28306502 - file:human/UVRAG/UVRAG-uniprot.txt - file:human/UVRAG/UVRAG-notes.md supported_by: - reference_id: PMID:28306502 supporting_text: Pacer recruits PI3KC3 and HOPS complexes to the autophagosome - reference_id: file:human/UVRAG/UVRAG-uniprot.txt supporting_text: Recruited to autophagosome following interaction with RUBCNL/PACER - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:28306502 qualifier: enables review: summary: The interaction evidence may be real, but generic protein binding is not an informative UVRAG function. action: MARK_AS_OVER_ANNOTATED 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. additional_reference_ids: - file:human/UVRAG/UVRAG-uniprot.txt - file:human/UVRAG/UVRAG-notes.md supported_by: - reference_id: file:human/UVRAG/UVRAG-uniprot.txt supporting_text: Component of the PI3K (PI3KC3/PI3K-III/class III - reference_id: file:human/UVRAG/UVRAG-uniprot.txt supporting_text: Interacts with VPS16; VPS11; VPS18; VPS33 - reference_id: file:human/UVRAG/UVRAG-uniprot.txt supporting_text: Interacts with PRKDC, XRCC6 and XRCC5 - term: id: GO:0097352 label: autophagosome maturation evidence_type: IDA original_reference_id: PMID:28306502 qualifier: involved_in review: summary: Autophagosome maturation is a core UVRAG process. action: ACCEPT reason: UVRAG coordinates PI3KC3/HOPS/class C VPS machinery and autophagosome-lysosome/endosome fusion during late autophagy. additional_reference_ids: - PMID:18552835 - PMID:28306502 - PMID:25533187 - file:human/UVRAG/UVRAG-uniprot.txt - file:human/UVRAG/UVRAG-notes.md supported_by: - reference_id: PMID:18552835 supporting_text: interacts with the class C Vps complex - reference_id: PMID:18552835 supporting_text: autophagosome fusion with late endosomes/lysosomes - reference_id: PMID:28306502 supporting_text: Pacer recruits PI3KC3 and HOPS complexes to the autophagosome - reference_id: file:human/UVRAG/UVRAG-uniprot.txt supporting_text: Involved in maturation of autophagosomes and degradative endocytic trafficking - reference_id: PMID:25533187 supporting_text: UVRAG is released from RUBICON to interact with the HOPS complex - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:28479384 qualifier: enables review: summary: The interaction evidence may be real, but generic protein binding is not an informative UVRAG function. action: MARK_AS_OVER_ANNOTATED 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. additional_reference_ids: - file:human/UVRAG/UVRAG-uniprot.txt - file:human/UVRAG/UVRAG-notes.md supported_by: - reference_id: file:human/UVRAG/UVRAG-uniprot.txt supporting_text: Component of the PI3K (PI3KC3/PI3K-III/class III - reference_id: file:human/UVRAG/UVRAG-uniprot.txt supporting_text: Interacts with VPS16; VPS11; VPS18; VPS33 - reference_id: file:human/UVRAG/UVRAG-uniprot.txt supporting_text: Interacts with PRKDC, XRCC6 and XRCC5 - term: id: GO:1901098 label: positive regulation of autophagosome maturation evidence_type: TAS original_reference_id: PMID:21118109 qualifier: involved_in review: summary: Positive regulation of autophagosome maturation is core and well supported. action: ACCEPT reason: UVRAG enhances autophagosome/endosome maturation via HOPS/class C VPS engagement and is released from inhibitory RUBICON interaction upon dephosphorylation. additional_reference_ids: - PMID:18552835 - PMID:25533187 - PMID:28306502 - file:human/UVRAG/UVRAG-uniprot.txt - file:human/UVRAG/UVRAG-notes.md supported_by: - reference_id: PMID:18552835 supporting_text: interacts with the class C Vps complex - reference_id: PMID:18552835 supporting_text: autophagosome fusion with late endosomes/lysosomes - reference_id: PMID:28306502 supporting_text: Pacer recruits PI3KC3 and HOPS complexes to the autophagosome - reference_id: file:human/UVRAG/UVRAG-uniprot.txt supporting_text: Involved in maturation of autophagosomes and degradative endocytic trafficking - reference_id: PMID:25533187 supporting_text: enhances autophagosome and endosome maturation - term: id: GO:0071985 label: multivesicular body sorting pathway evidence_type: TAS original_reference_id: PMID:21118109 qualifier: involved_in review: summary: Multivesicular body/endosomal sorting is supported but non-core in the PN autophagy review. action: KEEP_AS_NON_CORE reason: UVRAG contributes to degradative endocytic trafficking and endosome fusion, but the PN core is PI3KC3-C2/autophagosome maturation. additional_reference_ids: - PMID:18552835 - PMID:20643123 - file:human/UVRAG/UVRAG-uniprot.txt - file:human/UVRAG/UVRAG-notes.md supported_by: - reference_id: PMID:18552835 supporting_text: endosome-endosome fusion, resulting in rapid degradation of endocytic cargo - reference_id: PMID:20643123 supporting_text: regulates both receptor degradation and cytokinesis - term: id: GO:0005813 label: centrosome evidence_type: IDA original_reference_id: PMID:22542840 qualifier: located_in review: summary: Centrosome localization is supported but non-core. action: KEEP_AS_NON_CORE reason: UVRAG localizes to centrosomes and interacts with CEP63 in an autophagy-independent chromosome-stability branch. additional_reference_ids: - PMID:22542840 - file:human/UVRAG/UVRAG-uniprot.txt - file:human/UVRAG/UVRAG-notes.md supported_by: - reference_id: PMID:22542840 supporting_text: UVRAG promotes DNA double-strand-break repair by directly binding and activating - reference_id: PMID:22542840 supporting_text: centrosome instability and aneuploidy - reference_id: file:human/UVRAG/UVRAG-uniprot.txt supporting_text: Promotes DNA double-strand break (DSB) repair by association with DNA-dependent - term: id: GO:0006281 label: DNA repair evidence_type: IMP original_reference_id: PMID:22542840 qualifier: involved_in review: summary: DNA repair is supported for UVRAG but is an autophagy-independent non-core branch in this PN review. action: KEEP_AS_NON_CORE 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. additional_reference_ids: - PMID:22542840 - file:human/UVRAG/UVRAG-uniprot.txt - file:human/UVRAG/UVRAG-notes.md supported_by: - reference_id: PMID:22542840 supporting_text: UVRAG promotes DNA double-strand-break repair by directly binding and activating - reference_id: PMID:22542840 supporting_text: centrosome instability and aneuploidy - reference_id: file:human/UVRAG/UVRAG-uniprot.txt supporting_text: Promotes DNA double-strand break (DSB) repair by association with DNA-dependent - term: id: GO:0007098 label: centrosome cycle evidence_type: IMP original_reference_id: PMID:22542840 qualifier: involved_in review: summary: Centrosome cycle is supported as a non-core centrosome stability/chromosome segregation branch. action: KEEP_AS_NON_CORE reason: UVRAG interacts with CEP63 and is required for centrosome stability, but this is separate from the PN autophagy/endolysosomal core. additional_reference_ids: - PMID:22542840 - file:human/UVRAG/UVRAG-uniprot.txt - file:human/UVRAG/UVRAG-notes.md supported_by: - reference_id: PMID:22542840 supporting_text: UVRAG promotes DNA double-strand-break repair by directly binding and activating - reference_id: PMID:22542840 supporting_text: centrosome instability and aneuploidy - reference_id: file:human/UVRAG/UVRAG-uniprot.txt supporting_text: Promotes DNA double-strand break (DSB) repair by association with DNA-dependent - term: id: GO:0070418 label: DNA-dependent protein kinase complex evidence_type: IDA original_reference_id: PMID:22542840 qualifier: colocalizes_with review: summary: DNA-PK complex colocalization/association is supported but non-core. action: KEEP_AS_NON_CORE reason: UVRAG binds/activates DNA-PK for NHEJ, but this genome-stability function is outside the PN autophagosome maturation core. additional_reference_ids: - PMID:22542840 - file:human/UVRAG/UVRAG-uniprot.txt - file:human/UVRAG/UVRAG-notes.md supported_by: - reference_id: PMID:22542840 supporting_text: UVRAG promotes DNA double-strand-break repair by directly binding and activating - reference_id: PMID:22542840 supporting_text: centrosome instability and aneuploidy - reference_id: file:human/UVRAG/UVRAG-uniprot.txt supporting_text: Promotes DNA double-strand break (DSB) repair by association with DNA-dependent - term: id: GO:0071900 label: regulation of protein serine/threonine kinase activity evidence_type: IDA original_reference_id: PMID:22542840 qualifier: involved_in review: summary: Regulation of serine/threonine kinase activity is supported through DNA-PK activation but is broad and non-core. action: KEEP_AS_NON_CORE reason: The specific supported kinase is DNA-PK in NHEJ; this should not be interpreted as a core proteostasis/autophagy function. proposed_replacement_terms: - id: GO:0097680 label: double-strand break repair via classical nonhomologous end joining - id: GO:0006281 label: DNA repair additional_reference_ids: - PMID:22542840 - file:human/UVRAG/UVRAG-uniprot.txt - file:human/UVRAG/UVRAG-notes.md supported_by: - reference_id: PMID:22542840 supporting_text: UVRAG promotes DNA double-strand-break repair by directly binding and activating - reference_id: PMID:22542840 supporting_text: centrosome instability and aneuploidy - reference_id: file:human/UVRAG/UVRAG-uniprot.txt supporting_text: Promotes DNA double-strand break (DSB) repair by association with DNA-dependent - term: id: GO:0097680 label: double-strand break repair via classical nonhomologous end joining evidence_type: IDA original_reference_id: PMID:22542840 qualifier: involved_in review: summary: Classical NHEJ is supported for UVRAG but non-core. action: KEEP_AS_NON_CORE reason: UVRAG promotes DNA-PK-dependent NHEJ and chromosome stability, but this is a separate autophagy-independent branch. additional_reference_ids: - PMID:22542840 - file:human/UVRAG/UVRAG-uniprot.txt - file:human/UVRAG/UVRAG-notes.md supported_by: - reference_id: PMID:22542840 supporting_text: UVRAG promotes DNA double-strand-break repair by directly binding and activating - reference_id: PMID:22542840 supporting_text: centrosome instability and aneuploidy - reference_id: file:human/UVRAG/UVRAG-uniprot.txt supporting_text: Promotes DNA double-strand break (DSB) repair by association with DNA-dependent - term: id: GO:0030496 label: midbody evidence_type: IDA original_reference_id: PMID:20643123 qualifier: located_in review: summary: Midbody localization is supported for UVRAG cytokinesis biology but is not PN core. action: KEEP_AS_NON_CORE reason: The PI3KC3-C2/BIF-1-containing subcomplex has a supported cytokinesis/midbody branch; retain it as non-core relative to autophagosome maturation. additional_reference_ids: - PMID:20643123 - file:human/UVRAG/UVRAG-uniprot.txt - file:human/UVRAG/UVRAG-notes.md supported_by: - reference_id: PMID:20643123 supporting_text: strong localisation of these proteins to the midbody - reference_id: file:human/UVRAG/UVRAG-uniprot.txt supporting_text: Midbody - term: id: GO:0032465 label: regulation of cytokinesis evidence_type: IMP original_reference_id: PMID:20643123 qualifier: involved_in review: summary: Regulation of cytokinesis is supported through the UVRAG/BIF-1 PI3KC3 subcomplex but non-core. action: KEEP_AS_NON_CORE reason: The cytokinesis/midbody role is experimentally supported, but it is distinct from the PN autophagosome maturation function. additional_reference_ids: - PMID:20643123 - file:human/UVRAG/UVRAG-uniprot.txt - file:human/UVRAG/UVRAG-notes.md supported_by: - reference_id: PMID:20643123 supporting_text: regulates both receptor degradation and cytokinesis - reference_id: PMID:20643123 supporting_text: strong localisation of these proteins to the midbody - term: id: GO:0032801 label: receptor catabolic process evidence_type: IMP original_reference_id: PMID:20643123 qualifier: involved_in review: summary: Receptor catabolic process is supported but non-core. action: KEEP_AS_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. additional_reference_ids: - PMID:20643123 - PMID:25533187 - file:human/UVRAG/UVRAG-uniprot.txt - file:human/UVRAG/UVRAG-notes.md supported_by: - reference_id: PMID:20643123 supporting_text: regulates both receptor degradation and cytokinesis - reference_id: PMID:25533187 supporting_text: facilitates the lysosomal degradation of epidermal growth factor receptor - term: id: GO:0005783 label: endoplasmic reticulum evidence_type: IDA original_reference_id: PMID:24056303 qualifier: part_of review: summary: Endoplasmic reticulum localization is supported for the RINT1/NRZ retrograde trafficking branch. action: KEEP_AS_NON_CORE 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. additional_reference_ids: - PMID:24056303 - file:human/UVRAG/UVRAG-uniprot.txt - file:human/UVRAG/UVRAG-notes.md supported_by: - reference_id: PMID:24056303 supporting_text: PtdIns(3)P)-binding protein - reference_id: PMID:24056303 supporting_text: acts as an integral component of the RINT-1-containing ER tethering complex - reference_id: PMID:24056303 supporting_text: Bif-1-beclin-1-PI(3)KC3 complex to mobilize Atg9 translocation - term: id: GO:0006890 label: retrograde vesicle-mediated transport, Golgi to endoplasmic reticulum evidence_type: IMP original_reference_id: PMID:24056303 qualifier: involved_in review: summary: Golgi-to-ER retrograde transport is supported for UVRAG and retained as non-core trafficking biology. action: KEEP_AS_NON_CORE 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. additional_reference_ids: - PMID:24056303 - file:human/UVRAG/UVRAG-uniprot.txt - file:human/UVRAG/UVRAG-notes.md supported_by: - reference_id: PMID:24056303 supporting_text: PtdIns(3)P)-binding protein - reference_id: PMID:24056303 supporting_text: acts as an integral component of the RINT-1-containing ER tethering complex - reference_id: PMID:24056303 supporting_text: Bif-1-beclin-1-PI(3)KC3 complex to mobilize Atg9 translocation - term: id: GO:0006914 label: autophagy evidence_type: IMP original_reference_id: PMID:24056303 qualifier: involved_in review: summary: The PMID:24056303 evidence is better captured as ATG9/autophagy-related trafficking rather than broad autophagy. action: MODIFY 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_replacement_terms: - id: GO:0006890 label: retrograde vesicle-mediated transport, Golgi to endoplasmic reticulum - id: GO:0000045 label: autophagosome assembly additional_reference_ids: - PMID:24056303 - file:human/UVRAG/UVRAG-uniprot.txt - file:human/UVRAG/UVRAG-notes.md supported_by: - reference_id: PMID:24056303 supporting_text: PtdIns(3)P)-binding protein - reference_id: PMID:24056303 supporting_text: acts as an integral component of the RINT-1-containing ER tethering complex - reference_id: PMID:24056303 supporting_text: Bif-1-beclin-1-PI(3)KC3 complex to mobilize Atg9 translocation - term: id: GO:0051684 label: maintenance of Golgi location evidence_type: IMP original_reference_id: PMID:24056303 qualifier: involved_in review: summary: Maintenance of Golgi location is supported through the UVRAG/RINT1 retrograde trafficking branch but non-core. action: KEEP_AS_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. additional_reference_ids: - PMID:24056303 - file:human/UVRAG/UVRAG-uniprot.txt - file:human/UVRAG/UVRAG-notes.md supported_by: - reference_id: PMID:24056303 supporting_text: PtdIns(3)P)-binding protein - reference_id: PMID:24056303 supporting_text: acts as an integral component of the RINT-1-containing ER tethering complex - reference_id: PMID:24056303 supporting_text: Bif-1-beclin-1-PI(3)KC3 complex to mobilize Atg9 translocation - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:22354037 qualifier: enables review: summary: The interaction evidence may be real, but generic protein binding is not an informative UVRAG function. action: MARK_AS_OVER_ANNOTATED 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. additional_reference_ids: - file:human/UVRAG/UVRAG-uniprot.txt - file:human/UVRAG/UVRAG-notes.md supported_by: - reference_id: file:human/UVRAG/UVRAG-uniprot.txt supporting_text: Component of the PI3K (PI3KC3/PI3K-III/class III - reference_id: file:human/UVRAG/UVRAG-uniprot.txt supporting_text: Interacts with VPS16; VPS11; VPS18; VPS33 - reference_id: file:human/UVRAG/UVRAG-uniprot.txt supporting_text: Interacts with PRKDC, XRCC6 and XRCC5 - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:19270696 qualifier: enables review: summary: The interaction evidence may be real, but generic protein binding is not an informative UVRAG function. action: MARK_AS_OVER_ANNOTATED 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. additional_reference_ids: - file:human/UVRAG/UVRAG-uniprot.txt - file:human/UVRAG/UVRAG-notes.md supported_by: - reference_id: file:human/UVRAG/UVRAG-uniprot.txt supporting_text: Component of the PI3K (PI3KC3/PI3K-III/class III - reference_id: file:human/UVRAG/UVRAG-uniprot.txt supporting_text: Interacts with VPS16; VPS11; VPS18; VPS33 - reference_id: file:human/UVRAG/UVRAG-uniprot.txt supporting_text: Interacts with PRKDC, XRCC6 and XRCC5 - term: id: GO:0005764 label: lysosome evidence_type: IDA original_reference_id: PMID:19270696 qualifier: located_in review: summary: Lysosome localization is compatible with UVRAG late autophagy/endolysosomal trafficking. action: ACCEPT reason: UVRAG functions in autophagosome fusion with late endosomes/lysosomes and endocytic cargo delivery to degradative compartments. additional_reference_ids: - PMID:18552835 - file:human/UVRAG/UVRAG-uniprot.txt - file:human/UVRAG/UVRAG-notes.md supported_by: - reference_id: PMID:18552835 supporting_text: autophagosome fusion with late endosomes/lysosomes - reference_id: file:human/UVRAG/UVRAG-uniprot.txt supporting_text: Lysosome {ECO:0000269|PubMed:18843052} - term: id: GO:0005769 label: early endosome evidence_type: IDA original_reference_id: PMID:19270696 qualifier: located_in review: summary: Early endosome localization is supported for UVRAG endosomal trafficking biology. action: ACCEPT reason: UVRAG is found on endosomal compartments and contributes to endosome/endosome fusion and degradative endocytic trafficking. additional_reference_ids: - PMID:18552835 - PMID:18843052 - file:human/UVRAG/UVRAG-uniprot.txt - file:human/UVRAG/UVRAG-notes.md supported_by: - reference_id: PMID:18552835 supporting_text: endosome-endosome fusion, resulting in rapid degradation of endocytic cargo - reference_id: file:human/UVRAG/UVRAG-uniprot.txt supporting_text: Early endosome {ECO:0000269|PubMed:18552835 - term: id: GO:0005770 label: late endosome evidence_type: IDA original_reference_id: PMID:19270696 qualifier: located_in review: summary: Late endosome localization is supported and relevant to UVRAG autophagosome/endosome maturation. action: ACCEPT reason: The UVRAG-class C VPS/HOPS axis promotes autophagosome fusion with late endosomes/lysosomes and late endocytic fusion. additional_reference_ids: - PMID:18552835 - PMID:18843052 - file:human/UVRAG/UVRAG-uniprot.txt - file:human/UVRAG/UVRAG-notes.md supported_by: - reference_id: PMID:18552835 supporting_text: autophagosome fusion with late endosomes/lysosomes - reference_id: file:human/UVRAG/UVRAG-uniprot.txt supporting_text: Late endosome {ECO:0000269|PubMed:18843052} - term: id: GO:0005737 label: cytoplasm evidence_type: TAS original_reference_id: PMID:9169138 qualifier: located_in review: summary: Cytoplasm is a broad legacy localization for UVRAG. action: KEEP_AS_NON_CORE 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. proposed_replacement_terms: - id: GO:0005776 label: autophagosome - id: GO:0005769 label: early endosome - id: GO:0005770 label: late endosome additional_reference_ids: - PMID:9169138 - file:human/UVRAG/UVRAG-uniprot.txt - file:human/UVRAG/UVRAG-notes.md supported_by: - reference_id: PMID:9169138 supporting_text: novel 63-kDa cytoplasmic protein - reference_id: file:human/UVRAG/UVRAG-uniprot.txt supporting_text: Cytoplasmic vesicle, autophagosome - term: id: GO:0006281 label: DNA repair evidence_type: TAS original_reference_id: PMID:9169138 qualifier: involved_in review: summary: DNA repair is supported for UVRAG but is an autophagy-independent non-core branch in this PN review. action: KEEP_AS_NON_CORE 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. additional_reference_ids: - PMID:22542840 - file:human/UVRAG/UVRAG-uniprot.txt - file:human/UVRAG/UVRAG-notes.md supported_by: - reference_id: PMID:9169138 supporting_text: novel 63-kDa cytoplasmic protein - reference_id: PMID:22542840 supporting_text: UVRAG promotes DNA double-strand-break repair by directly binding and activating - term: id: GO:0030674 label: protein-macromolecule adaptor activity evidence_type: IDA original_reference_id: PMID:16799551 qualifier: enables review: summary: UVRAG has a supported adaptor/regulatory subunit role in PI3KC3-C2 and late fusion machinery. action: NEW 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. additional_reference_ids: - PMID:18552835 - PMID:18843052 - PMID:24550300 - PMID:28306502 - file:human/UVRAG/UVRAG-uniprot.txt - file:human/UVRAG/UVRAG-notes.md supported_by: - reference_id: PMID:16799551 supporting_text: positive regulator of the Beclin1-PI(3)KC3 complex - reference_id: PMID:18843052 supporting_text: Atg14, and UVRAG are not present in the same complex - reference_id: PMID:18552835 supporting_text: interacts with the class C Vps complex - reference_id: PMID:24550300 supporting_text: by assembling a specific fusogenic SNARE complex - reference_id: file:human/UVRAG/UVRAG-uniprot.txt supporting_text: acts as a regulatory subunit of the alternative PI3K complex II 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:0000107 title: Automatic transfer of experimentally verified manual GO annotation data to orthologs using Ensembl Compara findings: [] - id: GO_REF:0000117 title: Electronic Gene Ontology annotations created by ARBA machine learning models findings: [] - id: GO_REF:0000120 title: Combined Automated Annotation using Multiple IEA Methods findings: [] - id: PMID:16799551 title: Autophagic and tumour suppressor activity of a novel Beclin1-binding protein UVRAG. findings: [] - id: PMID:17891140 title: Bif-1 interacts with Beclin 1 through UVRAG and regulates autophagy and tumorigenesis. findings: [] - id: PMID:18552835 title: Beclin1-binding UVRAG targets the class C Vps complex to coordinate autophagosome maturation and endocytic trafficking. findings: [] - id: PMID:19050071 title: Identification of Barkor as a mammalian autophagy-specific factor for Beclin 1 and class III phosphatidylinositol 3-kinase. findings: [] - id: PMID:19270696 title: Two Beclin 1-binding proteins, Atg14L and Rubicon, reciprocally regulate autophagy at different stages. findings: [] - id: PMID:20562859 title: Network organization of the human autophagy system. findings: [] - id: PMID:20643123 title: A phosphatidylinositol 3-kinase class III sub-complex containing VPS15, VPS34, Beclin 1, UVRAG and BIF-1 regulates cytokinesis and degradative endocytic traffic. findings: [] - id: PMID:21062745 title: The RUN domain of rubicon is important for hVps34 binding, lipid kinase inhibition, and autophagy suppression. findings: [] - id: PMID:21118109 title: The role of ESCRT proteins in fusion events involving lysosomes, endosomes and autophagosomes. findings: [] - id: PMID:21597469 title: UV irradiation resistance-associated gene suppresses apoptosis by interfering with BAX activation. findings: [] - id: PMID:22081109 title: Inhibition of autophagy by TAB2 and TAB3. findings: [] - id: PMID:22354037 title: Genome-wide siRNA screen reveals amino acid starvation-induced autophagy requires SCOC and WAC. findings: [] - id: PMID:22493499 title: Receptor signaling lymphocyte-activation molecule family 1 (Slamf1) regulates membrane fusion and NADPH oxidase 2 (NOX2) activity by recruiting a Beclin-1/Vps34/ultraviolet radiation resistance-associated gene (UVRAG) complex. findings: [] - id: PMID:22542840 title: A dual role for UVRAG in maintaining chromosomal stability independent of autophagy. findings: [] - id: PMID:23954414 title: Beclin 2 functions in autophagy, degradation of G protein-coupled receptors, and metabolism. findings: [] - id: PMID:24034250 title: EGFR-mediated Beclin 1 phosphorylation in autophagy suppression, tumor progression, and tumor chemoresistance. findings: [] - id: PMID:24056303 title: PtdIns(3)P-bound UVRAG coordinates Golgi-ER retrograde and Atg9 transport by differential interactions with the ER tether and the beclin 1 complex. findings: [] - id: PMID:24554770 title: The HOPS complex mediates autophagosome-lysosome fusion through interaction with syntaxin 17. findings: [] - id: PMID:24785657 title: NRBF2 regulates macroautophagy as a component of Vps34 Complex I. findings: [] - id: PMID:24849286 title: NRBF2 regulates autophagy and prevents liver injury by modulating Atg14L-linked phosphatidylinositol-3 kinase III activity. findings: [] - id: PMID:25490155 title: Architecture and dynamics of the autophagic phosphatidylinositol 3-kinase complex. findings: [] - id: PMID:26496610 title: A human interactome in three quantitative dimensions organized by stoichiometries and abundances. findings: [] - id: PMID:28306502 title: Pacer Mediates the Function of Class III PI3K and HOPS Complexes in Autophagosome Maturation by Engaging Stx17. findings: [] - id: PMID:28479384 title: Beclin1 antagonizes LAPTM4B-mediated EGFR overactivation in gastric cancer cells. findings: [] - id: PMID:32296183 title: A reference map of the human binary protein interactome. findings: [] - id: PMID:33961781 title: Dual proteome-scale networks reveal cell-specific remodeling of the human interactome. findings: [] - id: PMID:34386498 title: ORF3a-Mediated Incomplete Autophagy Facilitates Severe Acute Respiratory Syndrome Coronavirus-2 Replication. findings: [] - id: PMID:35044719 title: Proteome-scale mapping of binding sites in the unstructured regions of the human proteome. findings: [] - id: PMID:35271311 title: 'OpenCell: Endogenous tagging for the cartography of human cellular organization.' findings: [] - id: PMID:37219487 title: Large-scale phosphomimetic screening identifies phospho-modulated motif-based protein interactions. findings: [] - id: PMID:8999962 title: Characterization of p150, an adaptor protein for the human phosphatidylinositol (PtdIns) 3-kinase. Substrate presentation by phosphatidylinositol transfer protein to the p150.Ptdins 3-kinase complex. findings: [] - id: PMID:9169138 title: Molecular cloning of a novel human gene encoding a 63-kDa protein and its sublocalization within the 11q13 locus. findings: [] - id: Reactome:R-HSA-9730505 title: SARS-CoV-2 3a binds to UVRAG findings: [] - id: PMID:18843052 title: Beclin 1 forms two distinct phosphatidylinositol 3-kinase complexes with mammalian Atg14 and UVRAG. findings: [] - id: PMID:24550300 title: UVRAG is required for virus entry through combinatorial interaction with the class C-Vps complex and SNAREs. findings: [] - id: PMID:25533187 title: mTORC1 phosphorylates UVRAG to negatively regulate autophagosome and endosome maturation. findings: [] - id: file:human/UVRAG/UVRAG-uniprot.txt title: UniProtKB record for human UVRAG findings: [] - id: file:human/UVRAG/UVRAG-notes.md title: UVRAG review notes findings: [] core_functions: - molecular_function: id: GO:0030674 label: protein-macromolecule adaptor activity description: UVRAG acts as the UVRAG-defining regulatory/adaptor subunit of PI3KC3-C2, linking PIK3C3/PIK3R4/BECN1 complex activity to PI3P-dependent endosomal and late autophagy trafficking. directly_involved_in: - id: GO:0036092 label: phosphatidylinositol-3-phosphate biosynthetic process - id: GO:0097352 label: autophagosome maturation - id: GO:1901098 label: positive regulation of autophagosome maturation - id: GO:0071985 label: multivesicular body sorting pathway locations: - id: GO:0005776 label: autophagosome - id: GO:0000421 label: autophagosome membrane - id: GO:0005769 label: early endosome - id: GO:0005770 label: late endosome - id: GO:0005764 label: lysosome in_complex: id: GO:0034272 label: phosphatidylinositol 3-kinase complex, class III, type II supported_by: - reference_id: PMID:16799551 supporting_text: positive regulator of the Beclin1-PI(3)KC3 complex - reference_id: PMID:18843052 supporting_text: Atg14, and UVRAG are not present in the same complex - reference_id: file:human/UVRAG/UVRAG-uniprot.txt supporting_text: acts as a regulatory subunit of the alternative PI3K complex II - reference_id: file:human/UVRAG/UVRAG-uniprot.txt supporting_text: mediates formation of phosphatidylinositol 3-phosphate - &id001 reference_id: PMID:18552835 supporting_text: interacts with the class C Vps complex - &id002 reference_id: PMID:18552835 supporting_text: autophagosome fusion with late endosomes/lysosomes - reference_id: PMID:28306502 supporting_text: Pacer recruits PI3KC3 and HOPS complexes to the autophagosome - reference_id: file:human/UVRAG/UVRAG-uniprot.txt supporting_text: Involved in maturation of autophagosomes and degradative endocytic trafficking - molecular_function: id: GO:0000149 label: SNARE binding description: UVRAG engages class C VPS/HOPS and endosomal/autophagosomal SNARE machinery to promote fusogenic SNARE complex assembly during late endosomal and autophagosome maturation events. directly_involved_in: - id: GO:0035493 label: SNARE complex assembly - id: GO:0097352 label: autophagosome maturation locations: - id: GO:0005770 label: late endosome - id: GO:0005764 label: lysosome - id: GO:0000421 label: autophagosome membrane supported_by: - reference_id: PMID:24550300 supporting_text: interactions with the class C vacuolar protein sorting (C-Vps) tethering complex and endosomal - reference_id: PMID:24550300 supporting_text: by assembling a specific fusogenic SNARE complex - reference_id: file:human/UVRAG/UVRAG-uniprot.txt supporting_text: SNARE complex and promotes fusogenic SNARE complex formation during - *id001 - *id002 proposed_new_terms: [] suggested_questions: - question: 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? experts: - GO autophagy editors - ComplexPortal curators - Reactome autophagy curators - question: 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? experts: - GO molecular function editors - autophagosome maturation experts - question: Should UVRAG DNA repair and centrosome annotations remain non-core in autophagy-focused reviews even though they are experimentally supported? experts: - GO DNA repair editors - GO autophagy editors suggested_experiments: - description: 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. experiment_type: UVRAG autophagy maturation separation-of-function rescue hypothesis: PI3KC3-C2 complex engagement and HOPS/SNARE engagement define separable UVRAG contributions to PI3P production and autophagosome maturation. - description: 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. experiment_type: parallel autophagy and genome-stability rescue assay hypothesis: UVRAG autophagosome maturation and DNA repair/centrosome functions are genetically separable branches rather than one shared autophagy-dependent phenotype.