{"entryType":"UniProtKB reviewed (Swiss-Prot)","primaryAccession":"Q9P2Y5","secondaryAccessions":["B3KTC1","O00392"],"uniProtkbId":"UVRAG_HUMAN","entryAudit":{"firstPublicDate":"2002-01-23","lastAnnotationUpdateDate":"2026-09-02","lastSequenceUpdateDate":"2000-10-01","entryVersion":183,"sequenceVersion":1},"annotationScore":5.0,"organism":{"scientificName":"Homo sapiens","commonName":"Human","taxonId":9606,"lineage":["Eukaryota","Metazoa","Chordata","Craniata","Vertebrata","Euteleostomi","Mammalia","Eutheria","Euarchontoglires","Primates","Haplorrhini","Catarrhini","Hominidae","Homo"]},"proteinExistence":"1: Evidence at protein level","proteinDescription":{"recommendedName":{"fullName":{"value":"UV radiation resistance-associated gene protein"}},"alternativeNames":[{"fullName":{"value":"p63"}}]},"genes":[{"geneName":{"value":"UVRAG"}}],"comments":[{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"18552835"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"20643123"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"24056303"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"28306502"},{"evidenceCode":"ECO:0000305"}],"value":"Versatile protein that is involved in regulation of different cellular pathways implicated in membrane trafficking. Involved in regulation of the COPI-dependent retrograde transport from Golgi and the endoplasmic reticulum by associating with the NRZ complex; the function is dependent on its binding to phosphatidylinositol 3-phosphate (PtdIns(3)P) (PubMed:16799551, PubMed:18552835, PubMed:20643123, PubMed:24056303, PubMed:28306502). During autophagy acts as a regulatory subunit of the alternative PI3K complex II (PI3KC3-C2) that mediates formation of phosphatidylinositol 3-phosphate and is believed to be involved in maturation of autophagosomes and endocytosis. Activates lipid kinase activity of PIK3C3 (PubMed:16799551, PubMed:20643123, PubMed:24056303, PubMed:28306502). Involved in the regulation of degradative endocytic trafficking and cytokinesis, and in regulation of ATG9A transport from the Golgi to the autophagosome; the functions seems to implicate its association with PI3KC3-C2 (PubMed:16799551, PubMed:20643123, PubMed:24056303). Involved in maturation of autophagosomes and degradative endocytic trafficking independently of BECN1 but depending on its association with a class C Vps complex (possibly the HOPS complex); the association is also proposed to promote autophagosome recruitment and activation of Rab7 and endosome-endosome fusion events (PubMed:18552835, PubMed:28306502). Enhances class C Vps complex (possibly HOPS complex) association with a SNARE complex and promotes fusogenic SNARE complex formation during late endocytic membrane fusion (PubMed:24550300). In case of negative-strand RNA virus infection is required for efficient virus entry, promotes endocytic transport of virions and is implicated in a VAMP8-specific fusogenic SNARE complex assembly (PubMed:24550300)"}],"commentType":"FUNCTION"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"22542840"}],"value":"Involved in maintaining chromosomal stability. Promotes DNA double-strand break (DSB) repair by association with DNA-dependent protein kinase complex DNA-PK and activating it in non-homologous end joining (NHEJ) (PubMed:22542840). Required for centrosome stability and proper chromosome segregation (PubMed:22542840)"}],"commentType":"FUNCTION"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"16799551"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"17891140"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"18552835"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"18843052"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"19050071"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"19270696"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"20643123"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"20974968"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"22354037"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"22493499"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"22542840"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"23878393"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"23954414"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"24056303"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"24550300"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"25533187"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"27911840"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"28306502"}],"value":"Component of the PI3K (PI3KC3/PI3K-III/class III phosphatidylinositol 3-kinase) complex II (PI3KC3-C2) in which the core composed of the catalytic subunit PIK3C3, the regulatory subunit PIK3R4 and BECN1 is associated with UVRAG; in the complex interacts directly with BECN1. PI3KC3-C2 can associate with further regulatory subunits such as RUBCN and probably SH3GLB1/Bif-1 (PubMed:16799551, PubMed:18843052, PubMed:19050071, PubMed:19270696, PubMed:20643123, PubMed:23878393, PubMed:24056303). Interacts with SH3GLB1; UVRAG bridges the interaction to BECN1 indicative for an association with the PI3K complex PI3KC3-C2 (PubMed:17891140). Interacts with RINT1. Associates with the NRZ complex under basal conditions and dissociates from it under autophagy conditions to associate with the PI3K complex; these complex associations seem to be mutually exclusive (PubMed:24056303). Interacts with VPS16; VPS11; VPS18; VPS33 (VPS33A or VPS33B) and VPS39; indicative for an association with a class C Vps tethering complex (possibly the HOPS complex) (PubMed:18552835, PubMed:25533187). Interacts with RAB7A; RAB7A competes with UVRAG for RUBCN binding (PubMed:20974968, PubMed:25533187). Interacts with STX7, VTI1B, STX8 (PubMed:24550300). Interacts with PRKDC, XRCC6 and XRCC5; indicative for an association with the DNA-dependent protein kinase complex DNA-PK. Interacts with CEP63 (PubMed:22542840). Directly interacts with FEZ1 and SCOC; the interaction with SCOC is reduced by amino acid starvation, but the complex is stabilized in the presence of FEZ1 (PubMed:22354037). Interacts with BECN1P1/BECN2 (PubMed:23954414). Interacts with SLAMF1 (PubMed:22493499). Interacts with RUBCNL/PACER; promoting targeting of UVRAG to autophagosome (PubMed:28306502). Interacts with WNK1 (PubMed:27911840)"}],"commentType":"SUBUNIT"},{"commentType":"INTERACTION","interactions":[{"interactantOne":{"uniProtKBAccession":"Q9P2Y5","intActId":"EBI-2952704"},"interactantTwo":{"uniProtKBAccession":"Q07812","geneName":"BAX","intActId":"EBI-516580"},"numberOfExperiments":6,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"Q9P2Y5","intActId":"EBI-2952704"},"interactantTwo":{"uniProtKBAccession":"Q14457","geneName":"BECN1","intActId":"EBI-949378"},"numberOfExperiments":47,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"Q9P2Y5","intActId":"EBI-2952704"},"interactantTwo":{"uniProtKBAccession":"P46934","geneName":"NEDD4","intActId":"EBI-726944"},"numberOfExperiments":2,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"Q9P2Y5","intActId":"EBI-2952704"},"interactantTwo":{"uniProtKBAccession":"Q8NEB9","geneName":"PIK3C3","intActId":"EBI-1056470"},"numberOfExperiments":25,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"Q9P2Y5","intActId":"EBI-2952704"},"interactantTwo":{"uniProtKBAccession":"Q6NUQ1","geneName":"RINT1","intActId":"EBI-726876"},"numberOfExperiments":18,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"Q9P2Y5","intActId":"EBI-2952704"},"interactantTwo":{"uniProtKBAccession":"Q92622","geneName":"RUBCN","intActId":"EBI-2952709"},"numberOfExperiments":11,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"Q9P2Y5","intActId":"EBI-2952704"},"interactantTwo":{"uniProtKBAccession":"Q9Y371","geneName":"SH3GLB1","intActId":"EBI-2623095"},"numberOfExperiments":11,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"Q9P2Y5","intActId":"EBI-2952704"},"interactantTwo":{"uniProtKBAccession":"Q96AX1","geneName":"VPS33A","intActId":"EBI-2527283"},"numberOfExperiments":4,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"Q9P2Y5","intActId":"EBI-2952704"},"interactantTwo":{"uniProtKBAccession":"P46937","geneName":"YAP1","intActId":"EBI-1044059"},"numberOfExperiments":2,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"Q9P2Y5","intActId":"EBI-2952704"},"interactantTwo":{"uniProtKBAccession":"P0DTC3","geneName":"3a","intActId":"EBI-25475894"},"numberOfExperiments":6,"organismDiffer":true},{"interactantOne":{"uniProtKBAccession":"Q9P2Y5","intActId":"EBI-2952704"},"interactantTwo":{"uniProtKBAccession":"Q9QUM4","geneName":"Slamf1","intActId":"EBI-7910086"},"numberOfExperiments":6,"organismDiffer":true}]},{"commentType":"SUBCELLULAR LOCATION","note":{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"24056303"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"28306502"}],"value":"Colocalizes with RAB9-positive compartments involved in retrograde transport from late endosomes to trans-Golgi network. Colocalization with early endosomes is only partial (PubMed:24056303). Recruited to autophagosome following interaction with RUBCNL/PACER (PubMed:28306502)"}]},"subcellularLocations":[{"location":{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"18843052"}],"value":"Late endosome","id":"SL-0152"}},{"location":{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"18843052"}],"value":"Lysosome","id":"SL-0158"}},{"location":{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"28306502"}],"value":"Cytoplasmic vesicle, autophagosome","id":"SL-0023"}},{"location":{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"18552835"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"18843052"}],"value":"Early endosome","id":"SL-0094"}},{"location":{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"24056303"}],"value":"Endoplasmic reticulum","id":"SL-0095"}},{"location":{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"20643123"}],"value":"Midbody","id":"SL-0469"}},{"location":{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"22542840"}],"value":"Chromosome, centromere","id":"SL-0047"}}]},{"commentType":"ALTERNATIVE PRODUCTS","events":["Alternative splicing"],"isoforms":[{"name":{"value":"1"},"isoformIds":["Q9P2Y5-1"],"isoformSequenceStatus":"Displayed"},{"name":{"value":"2"},"isoformIds":["Q9P2Y5-2"],"sequenceIds":["VSP_056176"],"isoformSequenceStatus":"Described"}]},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"10798355"}],"value":"Highly expressed in brain, lung, kidney and liver"}],"commentType":"TISSUE SPECIFICITY"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"25533187"}],"value":"Phosphorylated at Ser-498 by MTOR under basal conditions; increases the interaction with RUBCN implicated in inhibitory effect of RUBCN on PI3KC3 and decreases interaction with RAB7,A and VPS16 and VPS39 (indicative for a class C Vps complex, possibly the HOPS complex) (PubMed:25533187)"}],"commentType":"PTM"},{"commentType":"DISEASE","note":{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"10798355"}],"value":"A chromosomal aberration involving UVRAG has been observed in a patient with heterotaxy (left-right axis malformation). 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