ID UVRAG_HUMAN Reviewed; 699 AA. AC Q9P2Y5; B3KTC1; O00392; DT 23-JAN-2002, integrated into UniProtKB/Swiss-Prot. DT 01-OCT-2000, sequence version 1. DT 28-JAN-2026, entry version 181. DE RecName: Full=UV radiation resistance-associated gene protein; DE AltName: Full=p63; GN Name=UVRAG; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RX PubMed=9169138; DOI=10.1006/geno.1997.4623; RA Perelman B., Dafni N., Naiman T., Eli D., Yaakov M., Feng T.L.Y., Sinha S., RA Weber G., Khodaei S., Sancar A., Dotan I., Canaani D.; RT "Molecular cloning of a novel human gene encoding a 63-kDa protein and its RT sublocalization within the 11q13 locus."; RL Genomics 41:397-405(1997). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), TISSUE SPECIFICITY, AND POSSIBLE RP INVOLVEMENT IN HETEROTAXY. RC TISSUE=Heart; RX PubMed=10798355; DOI=10.1007/s004390051038; RA Iida A., Emi M., Matsuoka R., Hiratsuka E., Okui K., Ohashi H., Inazawa J., RA Fukushima Y., Imai T., Nakamura Y.; RT "Identification of a gene disrupted by inv(11)(q13.5;q25) in a patient with RT left-right axis malformation."; RL Hum. Genet. 106:277-287(2000). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). RC TISSUE=Tongue; RX PubMed=14702039; DOI=10.1038/ng1285; RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S., RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., RA Isogai T., Sugano S.; RT "Complete sequencing and characterization of 21,243 full-length human RT cDNAs."; RL Nat. Genet. 36:40-45(2004). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=16554811; DOI=10.1038/nature04632; RA Taylor T.D., Noguchi H., Totoki Y., Toyoda A., Kuroki Y., Dewar K., RA Lloyd C., Itoh T., Takeda T., Kim D.-W., She X., Barlow K.F., Bloom T., RA Bruford E., Chang J.L., Cuomo C.A., Eichler E., FitzGerald M.G., RA Jaffe D.B., LaButti K., Nicol R., Park H.-S., Seaman C., Sougnez C., RA Yang X., Zimmer A.R., Zody M.C., Birren B.W., Nusbaum C., Fujiyama A., RA Hattori M., Rogers J., Lander E.S., Sakaki Y.; RT "Human chromosome 11 DNA sequence and analysis including novel gene RT identification."; RL Nature 440:497-500(2006). RN [5] RP ASSOCIATION WITH THE PI3K COMPLEX, AND FUNCTION. RX PubMed=16799551; DOI=10.1038/ncb1426; RA Liang C., Feng P., Ku B., Dotan I., Canaani D., Oh B.H., Jung J.U.; RT "Autophagic and tumour suppressor activity of a novel Beclin1-binding RT protein UVRAG."; RL Nat. Cell Biol. 8:688-699(2006). RN [6] RP INTERACTION WITH SH3GLB1. RX PubMed=17891140; DOI=10.1038/ncb1634; RA Takahashi Y., Coppola D., Matsushita N., Cualing H.D., Sun M., Sato Y., RA Liang C., Jung J.U., Cheng J.Q., Mule J.J., Pledger W.J., Wang H.G.; RT "Bif-1 interacts with Beclin 1 through UVRAG and regulates autophagy and RT tumorigenesis."; RL Nat. Cell Biol. 9:1142-1151(2007). RN [7] RP INTERACTION WITH BECN1 AND PIK3C3, AND SUBCELLULAR LOCATION. RX PubMed=18843052; DOI=10.1091/mbc.e08-01-0080; RA Itakura E., Kishi C., Inoue K., Mizushima N.; RT "Beclin 1 forms two distinct phosphatidylinositol 3-kinase complexes with RT mammalian Atg14 and UVRAG."; RL Mol. Biol. Cell 19:5360-5372(2008). RN [8] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-498, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=18691976; DOI=10.1016/j.molcel.2008.07.007; RA Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R., RA Greff Z., Keri G., Stemmann O., Mann M.; RT "Kinase-selective enrichment enables quantitative phosphoproteomics of the RT kinome across the cell cycle."; RL Mol. Cell 31:438-448(2008). RN [9] RP FUNCTION, INTERACTION WITH VPS16; VPS11; VPS18; VPS33 AND VPS39, AND RP SUBCELLULAR LOCATION. RX PubMed=18552835; DOI=10.1038/ncb1740; RA Liang C., Lee J.S., Inn K.S., Gack M.U., Li Q., Roberts E.A., Vergne I., RA Deretic V., Feng P., Akazawa C., Jung J.U.; RT "Beclin1-binding UVRAG targets the class C Vps complex to coordinate RT autophagosome maturation and endocytic trafficking."; RL Nat. Cell Biol. 10:776-787(2008). RN [10] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-518, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=18669648; DOI=10.1073/pnas.0805139105; RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., RA Elledge S.J., Gygi S.P.; RT "A quantitative atlas of mitotic phosphorylation."; RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008). RN [11] RP INTERACTION WITH BECN1. RX PubMed=19050071; DOI=10.1073/pnas.0810452105; RA Sun Q., Fan W., Chen K., Ding X., Chen S., Zhong Q.; RT "Identification of Barkor as a mammalian autophagy-specific factor for RT Beclin 1 and class III phosphatidylinositol 3-kinase."; RL Proc. Natl. Acad. Sci. U.S.A. 105:19211-19216(2008). RN [12] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-498 AND SER-571, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=19369195; DOI=10.1074/mcp.m800588-mcp200; RA Oppermann F.S., Gnad F., Olsen J.V., Hornberger R., Greff Z., Keri G., RA Mann M., Daub H.; RT "Large-scale proteomics analysis of the human kinome."; RL Mol. Cell. Proteomics 8:1751-1764(2009). RN [13] RP INTERACTION WITH BECN1; RUBCN; PIK3C3 AND PIK3R4. RX PubMed=19270696; DOI=10.1038/ncb1846; RA Matsunaga K., Saitoh T., Tabata K., Omori H., Satoh T., Kurotori N., RA Maejima I., Shirahama-Noda K., Ichimura T., Isobe T., Akira S., Noda T., RA Yoshimori T.; RT "Two Beclin 1-binding proteins, Atg14L and Rubicon, reciprocally regulate RT autophagy at different stages."; RL Nat. Cell Biol. 11:385-396(2009). RN [14] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-518, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Leukemic T-cell; RX PubMed=19690332; DOI=10.1126/scisignal.2000007; RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., RA Rodionov V., Han D.K.; RT "Quantitative phosphoproteomic analysis of T cell receptor signaling RT reveals system-wide modulation of protein-protein interactions."; RL Sci. Signal. 2:RA46-RA46(2009). RN [15] RP FUNCTION, SUBUNIT, AND SUBCELLULAR LOCATION. RX PubMed=20643123; DOI=10.1016/j.yexcr.2010.07.008; RA Thoresen S.B., Pedersen N.M., Liestol K., Stenmark H.; RT "A phosphatidylinositol 3-kinase class III sub-complex containing VPS15, RT VPS34, Beclin 1, UVRAG and BIF-1 regulates cytokinesis and degradative RT endocytic traffic."; RL Exp. Cell Res. 316:3368-3378(2010). RN [16] RP INTERACTION WITH RAB7A. RX PubMed=20974968; DOI=10.1073/pnas.1010554107; RA Sun Q., Westphal W., Wong K.N., Tan I., Zhong Q.; RT "Rubicon controls endosome maturation as a Rab7 effector."; RL Proc. Natl. Acad. Sci. U.S.A. 107:19338-19343(2010). RN [17] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-498, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=20068231; DOI=10.1126/scisignal.2000475; RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.; RT "Quantitative phosphoproteomics reveals widespread full phosphorylation RT site occupancy during mitosis."; RL Sci. Signal. 3:RA3-RA3(2010). RN [18] RP FUNCTION, INTERACTION WITH PRKDC; XRCC6; XRCC5 AND CEP63, AND SUBCELLULAR RP LOCATION. RX PubMed=22542840; DOI=10.1016/j.devcel.2011.12.027; RA Zhao Z., Oh S., Li D., Ni D., Pirooz S.D., Lee J.H., Yang S., Lee J.Y., RA Ghozalli I., Costanzo V., Stark J.M., Liang C.; RT "A dual role for UVRAG in maintaining chromosomal stability independent of RT autophagy."; RL Dev. Cell 22:1001-1016(2012). RN [19] RP INTERACTION WITH SCOC AND FEZ1. RX PubMed=22354037; DOI=10.1038/emboj.2012.36; RA McKnight N.C., Jefferies H.B., Alemu E.A., Saunders R.E., Howell M., RA Johansen T., Tooze S.A.; RT "Genome-wide siRNA screen reveals amino acid starvation-induced autophagy RT requires SCOC and WAC."; RL EMBO J. 31:1931-1946(2012). RN [20] RP INTERACTION WITH SLAMF1. RX PubMed=22493499; DOI=10.1074/jbc.m112.367060; RA Ma C., Wang N., Detre C., Wang G., O'Keeffe M., Terhorst C.; RT "Receptor signaling lymphocyte-activation molecule family 1 (Slamf1) RT regulates membrane fusion and NADPH oxidase 2 (NOX2) activity by recruiting RT a Beclin-1/Vps34/ultraviolet radiation resistance-associated gene (UVRAG) RT complex."; RL J. Biol. Chem. 287:18359-18365(2012). RN [21] RP INTERACTION WITH BECN1P1/BECN2. RX PubMed=23954414; DOI=10.1016/j.cell.2013.07.035; RA He C., Wei Y., Sun K., Li B., Dong X., Zou Z., Liu Y., Kinch L.N., Khan S., RA Sinha S., Xavier R.J., Grishin N.V., Xiao G., Eskelinen E.L., Scherer P.E., RA Whistler J.L., Levine B.; RT "Beclin 2 functions in autophagy, degradation of G protein-coupled RT receptors, and metabolism."; RL Cell 154:1085-1099(2013). RN [22] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-498; THR-518; SER-550 AND RP SER-689, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma, and Erythroleukemia; RX PubMed=23186163; DOI=10.1021/pr300630k; RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J., RA Mohammed S.; RT "Toward a comprehensive characterization of a human cancer cell RT phosphoproteome."; RL J. Proteome Res. 12:260-271(2013). RN [23] RP INTERACTION WITH BECN1. RX PubMed=23878393; DOI=10.1128/mcb.00079-13; RA Fogel A.I., Dlouhy B.J., Wang C., Ryu S.W., Neutzner A., Hasson S.A., RA Sideris D.P., Abeliovich H., Youle R.J.; RT "Role of membrane association and Atg14-dependent phosphorylation in RT beclin-1-mediated autophagy."; RL Mol. Cell. Biol. 33:3675-3688(2013). RN [24] RP FUNCTION, INTERACTION WITH RINT1, SUBCELLULAR LOCATION, ASSOCIATION WITH RP THE PI3K COMPLEX, AND ASSOCIATION WITH THE NRZ COMPLEX. RX PubMed=24056303; DOI=10.1038/ncb2848; RA He S., Ni D., Ma B., Lee J.H., Zhang T., Ghozalli I., Pirooz S.D., Zhao Z., RA Bharatham N., Li B., Oh S., Lee W.H., Takahashi Y., Wang H.G., RA Minassian A., Feng P., Deretic V., Pepperkok R., Tagaya M., Yoon H.S., RA Liang C.; RT "PtdIns(3)P-bound UVRAG coordinates Golgi-ER retrograde and Atg9 transport RT by differential interactions with the ER tether and the beclin 1 complex."; RL Nat. Cell Biol. 15:1206-1219(2013). RN [25] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Liver; RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014; RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L., RA Ye M., Zou H.; RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver RT phosphoproteome."; RL J. Proteomics 96:253-262(2014). RN [26] RP FUNCTION, AND INTERACTION WITH STX7; VTI1B AND STX8. RX PubMed=24550300; DOI=10.1073/pnas.1320629111; RA Pirooz S.D., He S., Zhang T., Zhang X., Zhao Z., Oh S., O'Connell D., RA Khalilzadeh P., Amini-Bavil-Olyaee S., Farzan M., Liang C.; RT "UVRAG is required for virus entry through combinatorial interaction with RT the class C-Vps complex and SNAREs."; RL Proc. Natl. Acad. Sci. U.S.A. 111:2716-2721(2014). RN [27] RP PHOSPHORYLATION AT SER-493; SER-498; SER-508; SER-522; SER-549; SER-550 AND RP SER-582, INTERACTION WITH RUBCN; VPS39; VPS16 AND RAB7A, AND MUTAGENESIS OF RP SER-498. RX PubMed=25533187; DOI=10.1016/j.molcel.2014.11.013; RA Kim Y.M., Jung C.H., Seo M., Kim E.K., Park J.M., Bae S.S., Kim D.H.; RT "mTORC1 phosphorylates UVRAG to negatively regulate autophagosome and RT endosome maturation."; RL Mol. Cell 57:207-218(2015). RN [28] RP INTERACTION WITH WNK1. RX PubMed=27911840; DOI=10.1073/pnas.1617649113; RA Gallolu Kankanamalage S., Lee A.Y., Wichaidit C., Lorente-Rodriguez A., RA Shah A.M., Stippec S., Whitehurst A.W., Cobb M.H.; RT "Multistep regulation of autophagy by WNK1."; RL Proc. Natl. Acad. Sci. U.S.A. 113:14342-14347(2016). RN [29] RP FUNCTION, INTERACTION WITH RUBCNL/PACER, AND SUBCELLULAR LOCATION. RX PubMed=28306502; DOI=10.1016/j.molcel.2017.02.010; RA Cheng X., Ma X., Ding X., Li L., Jiang X., Shen Z., Chen S., Liu W., RA Gong W., Sun Q.; RT "Pacer mediates the function of class III PI3K and HOPS complexes in RT autophagosome maturation by engaging Stx17."; RL Mol. Cell 65:1029-1043(2017). CC -!- FUNCTION: Versatile protein that is involved in regulation of different CC cellular pathways implicated in membrane trafficking. Involved in CC regulation of the COPI-dependent retrograde transport from Golgi and CC the endoplasmic reticulum by associating with the NRZ complex; the CC function is dependent on its binding to phosphatidylinositol 3- CC phosphate (PtdIns(3)P) (PubMed:16799551, PubMed:18552835, CC PubMed:20643123, PubMed:24056303, PubMed:28306502). During autophagy CC acts as a regulatory subunit of the alternative PI3K complex II CC (PI3KC3-C2) that mediates formation of phosphatidylinositol 3-phosphate CC and is believed to be involved in maturation of autophagosomes and CC endocytosis. Activates lipid kinase activity of PIK3C3 CC (PubMed:16799551, PubMed:20643123, PubMed:24056303, PubMed:28306502). CC Involved in the regulation of degradative endocytic trafficking and CC cytokinesis, and in regulation of ATG9A transport from the Golgi to the CC autophagosome; the functions seems to implicate its association with CC PI3KC3-C2 (PubMed:16799551, PubMed:20643123, PubMed:24056303). Involved CC in maturation of autophagosomes and degradative endocytic trafficking CC independently of BECN1 but depending on its association with a class C CC Vps complex (possibly the HOPS complex); the association is also CC proposed to promote autophagosome recruitment and activation of Rab7 CC and endosome-endosome fusion events (PubMed:18552835, PubMed:28306502). CC Enhances class C Vps complex (possibly HOPS complex) association with a CC SNARE complex and promotes fusogenic SNARE complex formation during CC late endocytic membrane fusion (PubMed:24550300). In case of negative- CC strand RNA virus infection is required for efficient virus entry, CC promotes endocytic transport of virions and is implicated in a VAMP8- CC specific fusogenic SNARE complex assembly (PubMed:24550300). CC {ECO:0000269|PubMed:18552835, ECO:0000269|PubMed:20643123, CC ECO:0000269|PubMed:24056303, ECO:0000269|PubMed:28306502, ECO:0000305}. CC -!- FUNCTION: Involved in maintaining chromosomal stability. Promotes DNA CC double-strand break (DSB) repair by association with DNA-dependent CC protein kinase complex DNA-PK and activating it in non-homologous end CC joining (NHEJ) (PubMed:22542840). Required for centrosome stability and CC proper chromosome segregation (PubMed:22542840). CC {ECO:0000269|PubMed:22542840}. CC -!- SUBUNIT: Component of the PI3K (PI3KC3/PI3K-III/class III CC phosphatidylinositol 3-kinase) complex II (PI3KC3-C2) in which the core CC composed of the catalytic subunit PIK3C3, the regulatory subunit PIK3R4 CC and BECN1 is associated with UVRAG; in the complex interacts directly CC with BECN1. PI3KC3-C2 can associate with further regulatory subunits CC such as RUBCN and probably SH3GLB1/Bif-1 (PubMed:16799551, CC PubMed:18843052, PubMed:19050071, PubMed:19270696, PubMed:20643123, CC PubMed:23878393, PubMed:24056303). Interacts with SH3GLB1; UVRAG CC bridges the interaction to BECN1 indicative for an association with the CC PI3K complex PI3KC3-C2 (PubMed:17891140). Interacts with RINT1. CC Associates with the NRZ complex under basal conditions and dissociates CC from it under autophagy conditions to associate with the PI3K complex; CC these complex associations seem to be mutually exclusive CC (PubMed:24056303). Interacts with VPS16; VPS11; VPS18; VPS33 (VPS33A or CC VPS33B) and VPS39; indicative for an association with a class C Vps CC tethering complex (possibly the HOPS complex) (PubMed:18552835, CC PubMed:25533187). Interacts with RAB7A; RAB7A competes with UVRAG for CC RUBCN binding (PubMed:20974968, PubMed:25533187). Interacts with STX7, CC VTI1B, STX8 (PubMed:24550300). Interacts with PRKDC, XRCC6 and XRCC5; CC indicative for an association with the DNA-dependent protein kinase CC complex DNA-PK. Interacts with CEP63 (PubMed:22542840). Directly CC interacts with FEZ1 and SCOC; the interaction with SCOC is reduced by CC amino acid starvation, but the complex is stabilized in the presence of CC FEZ1 (PubMed:22354037). Interacts with BECN1P1/BECN2 (PubMed:23954414). CC Interacts with SLAMF1 (PubMed:22493499). Interacts with RUBCNL/PACER; CC promoting targeting of UVRAG to autophagosome (PubMed:28306502). CC Interacts with WNK1 (PubMed:27911840). {ECO:0000269|PubMed:16799551, CC ECO:0000269|PubMed:17891140, ECO:0000269|PubMed:18552835, CC ECO:0000269|PubMed:18843052, ECO:0000269|PubMed:19050071, CC ECO:0000269|PubMed:19270696, ECO:0000269|PubMed:20643123, CC ECO:0000269|PubMed:20974968, ECO:0000269|PubMed:22354037, CC ECO:0000269|PubMed:22493499, ECO:0000269|PubMed:22542840, CC ECO:0000269|PubMed:23878393, ECO:0000269|PubMed:23954414, CC ECO:0000269|PubMed:24056303, ECO:0000269|PubMed:24550300, CC ECO:0000269|PubMed:25533187, ECO:0000269|PubMed:27911840, CC ECO:0000269|PubMed:28306502}. CC -!- INTERACTION: CC Q9P2Y5; Q07812: BAX; NbExp=6; IntAct=EBI-2952704, EBI-516580; CC Q9P2Y5; Q14457: BECN1; NbExp=47; IntAct=EBI-2952704, EBI-949378; CC Q9P2Y5; P46934: NEDD4; NbExp=2; IntAct=EBI-2952704, EBI-726944; CC Q9P2Y5; Q8NEB9: PIK3C3; NbExp=25; IntAct=EBI-2952704, EBI-1056470; CC Q9P2Y5; Q6NUQ1: RINT1; NbExp=18; IntAct=EBI-2952704, EBI-726876; CC Q9P2Y5; Q92622: RUBCN; NbExp=11; IntAct=EBI-2952704, EBI-2952709; CC Q9P2Y5; Q9Y371: SH3GLB1; NbExp=11; IntAct=EBI-2952704, EBI-2623095; CC Q9P2Y5; Q96AX1: VPS33A; NbExp=4; IntAct=EBI-2952704, EBI-2527283; CC Q9P2Y5; P46937: YAP1; NbExp=2; IntAct=EBI-2952704, EBI-1044059; CC Q9P2Y5; P0DTC3: 3a; Xeno; NbExp=6; IntAct=EBI-2952704, EBI-25475894; CC Q9P2Y5; Q9QUM4: Slamf1; Xeno; NbExp=6; IntAct=EBI-2952704, EBI-7910086; CC -!- SUBCELLULAR LOCATION: Late endosome {ECO:0000269|PubMed:18843052}. CC Lysosome {ECO:0000269|PubMed:18843052}. Cytoplasmic vesicle, CC autophagosome {ECO:0000269|PubMed:28306502}. Early endosome CC {ECO:0000269|PubMed:18552835, ECO:0000269|PubMed:18843052}. Endoplasmic CC reticulum {ECO:0000269|PubMed:24056303}. Midbody CC {ECO:0000269|PubMed:20643123}. Chromosome, centromere CC {ECO:0000269|PubMed:22542840}. Note=Colocalizes with RAB9-positive CC compartments involved in retrograde transport from late endosomes to CC trans-Golgi network. Colocalization with early endosomes is only CC partial (PubMed:24056303). Recruited to autophagosome following CC interaction with RUBCNL/PACER (PubMed:28306502). CC {ECO:0000269|PubMed:24056303, ECO:0000269|PubMed:28306502}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=1; CC IsoId=Q9P2Y5-1; Sequence=Displayed; CC Name=2; CC IsoId=Q9P2Y5-2; Sequence=VSP_056176; CC -!- TISSUE SPECIFICITY: Highly expressed in brain, lung, kidney and liver. CC {ECO:0000269|PubMed:10798355}. CC -!- PTM: Phosphorylated at Ser-498 by MTOR under basal conditions; CC increases the interaction with RUBCN implicated in inhibitory effect of CC RUBCN on PI3KC3 and decreases interaction with RAB7,A and VPS16 and CC VPS39 (indicative for a class C Vps complex, possibly the HOPS complex) CC (PubMed:25533187). {ECO:0000269|PubMed:25533187}. CC -!- DISEASE: Note=A chromosomal aberration involving UVRAG has been CC observed in a patient with heterotaxy (left-right axis malformation). CC Inversion Inv(11)(q13.5;q25). {ECO:0000269|PubMed:10798355}. CC -!- SEQUENCE CAUTION: CC Sequence=CAA67507.1; Type=Erroneous gene model prediction; Evidence={ECO:0000305}; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; X99050; CAA67507.1; ALT_SEQ; Genomic_DNA. DR EMBL; AB012958; BAA90829.1; -; mRNA. DR EMBL; AK095352; BAG53033.1; -; mRNA. DR EMBL; AK296871; BAG59434.1; -; mRNA. DR EMBL; AK316133; BAH14504.1; -; mRNA. DR EMBL; AP002340; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AP003031; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AP003168; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR CCDS; CCDS8241.1; -. [Q9P2Y5-1] DR RefSeq; NP_003360.2; NM_003369.3. [Q9P2Y5-1] DR RefSeq; XP_047283478.1; XM_047427522.1. [Q9P2Y5-2] DR RefSeq; XP_054225793.1; XM_054369818.1. [Q9P2Y5-2] DR PDB; 7BL1; EM; 9.80 A; AAA=1-699. DR PDBsum; 7BL1; -. DR AlphaFoldDB; Q9P2Y5; -. DR EMDB; EMD-12214; -. DR EMDB; EMD-12237; -. DR EMDB; EMD-12238; -. DR SMR; Q9P2Y5; -. DR BioGRID; 113248; 69. DR ComplexPortal; CPX-74; Phosphatidylinositol 3-kinase complex, class III, UVRAG variant. DR CORUM; Q9P2Y5; -. DR DIP; DIP-48652N; -. DR FunCoup; Q9P2Y5; 2363. DR IntAct; Q9P2Y5; 85. DR MINT; Q9P2Y5; -. DR STRING; 9606.ENSP00000348455; -. DR ChEMBL; CHEMBL4296018; -. DR iPTMnet; Q9P2Y5; -. DR PhosphoSitePlus; Q9P2Y5; -. DR BioMuta; UVRAG; -. DR DMDM; 20140879; -. DR jPOST; Q9P2Y5; -. DR MassIVE; Q9P2Y5; -. DR PaxDb; 9606-ENSP00000348455; -. DR PeptideAtlas; Q9P2Y5; -. DR ProteomicsDB; 3674; -. DR ProteomicsDB; 83914; -. [Q9P2Y5-1] DR Pumba; Q9P2Y5; -. DR Antibodypedia; 2165; 400 antibodies from 38 providers. DR DNASU; 7405; -. DR Ensembl; ENST00000356136.8; ENSP00000348455.3; ENSG00000198382.10. [Q9P2Y5-1] DR Ensembl; ENST00000531818.5; ENSP00000434082.1; ENSG00000198382.10. [Q9P2Y5-2] DR Ensembl; ENST00000532130.1; ENSP00000436270.1; ENSG00000198382.10. [Q9P2Y5-2] DR Ensembl; ENST00000533454.5; ENSP00000431256.1; ENSG00000198382.10. [Q9P2Y5-2] DR GeneID; 7405; -. DR KEGG; hsa:7405; -. DR MANE-Select; ENST00000356136.8; ENSP00000348455.3; NM_003369.4; NP_003360.2. DR UCSC; uc001oxc.4; human. [Q9P2Y5-1] DR AGR; HGNC:12640; -. DR ClinPGx; PA37264; -. DR CTD; 7405; -. DR DisGeNET; 7405; -. DR GeneCards; UVRAG; -. DR HGNC; HGNC:12640; UVRAG. DR HPA; ENSG00000198382; Low tissue specificity. DR MIM; 602493; gene. DR OpenTargets; ENSG00000198382; -. DR VEuPathDB; HostDB:ENSG00000198382; -. DR eggNOG; KOG2896; Eukaryota. DR GeneTree; ENSGT00390000012877; -. DR HOGENOM; CLU_009375_2_0_1; -. DR InParanoid; Q9P2Y5; -. DR OMA; HVDQNCV; -. DR OrthoDB; 72772at2759; -. DR PAN-GO; Q9P2Y5; 4 GO annotations based on evolutionary models. DR PhylomeDB; Q9P2Y5; -. DR BRENDA; 2.7.1.137; 2681. DR PathwayCommons; Q9P2Y5; -. DR Reactome; R-HSA-1632852; Macroautophagy. DR Reactome; R-HSA-9679504; Translation of Replicase and Assembly of the Replication Transcription Complex. DR Reactome; R-HSA-9694676; Translation of Replicase and Assembly of the Replication Transcription Complex. DR Reactome; R-HSA-9754560; SARS-CoV-2 modulates autophagy. DR SignaLink; Q9P2Y5; -. DR SIGNOR; Q9P2Y5; -. DR Agora; ENSG00000198382; -. DR BioGRID-ORCS; 7405; 97 hits in 1181 CRISPR screens. DR ChiTaRS; UVRAG; human. DR GeneWiki; UVRAG; -. DR GenomeRNAi; 7405; -. DR Pharos; Q9P2Y5; Tbio. DR PRO; PR:Q9P2Y5; -. DR Proteomes; UP000005640; Chromosome 11. DR RNAct; Q9P2Y5; protein. DR Bgee; ENSG00000198382; Expressed in adrenal tissue and 198 other cell types or tissues. DR ExpressionAtlas; Q9P2Y5; baseline and differential. DR GO; GO:0000421; C:autophagosome membrane; IDA:UniProtKB. DR GO; GO:0005813; C:centrosome; IDA:UniProtKB. DR GO; GO:0000775; C:chromosome, centromeric region; IEA:UniProtKB-SubCell. DR GO; GO:0005737; C:cytoplasm; TAS:ProtInc. DR GO; GO:0005769; C:early endosome; IDA:UniProtKB. DR GO; GO:0005783; C:endoplasmic reticulum; IDA:CACAO. DR GO; GO:0033116; C:endoplasmic reticulum-Golgi intermediate compartment membrane; TAS:Reactome. DR GO; GO:0005768; C:endosome; IBA:GO_Central. DR GO; GO:0005770; C:late endosome; IDA:UniProtKB. DR GO; GO:0005764; C:lysosome; IDA:UniProtKB. DR GO; GO:0000323; C:lytic vacuole; IBA:GO_Central. DR GO; GO:0030496; C:midbody; IDA:UniProtKB. DR GO; GO:0045335; C:phagocytic vesicle; IEA:Ensembl. DR GO; GO:0035032; C:phosphatidylinositol 3-kinase complex, class III; IPI:ComplexPortal. DR GO; GO:0017124; F:SH3 domain binding; IEA:Ensembl. DR GO; GO:0000149; F:SNARE binding; IBA:GO_Central. DR GO; GO:0097352; P:autophagosome maturation; IDA:UniProtKB. DR GO; GO:0006914; P:autophagy; IMP:CACAO. DR GO; GO:0007098; P:centrosome cycle; IMP:UniProtKB. DR GO; GO:0007059; P:chromosome segregation; IEA:Ensembl. DR GO; GO:0006281; P:DNA repair; IMP:UniProtKB. DR GO; GO:0097680; P:double-strand break repair via classical nonhomologous end joining; IDA:UniProtKB. DR GO; GO:0051684; P:maintenance of Golgi location; IMP:CACAO. DR GO; GO:0071985; P:multivesicular body sorting pathway; TAS:ParkinsonsUK-UCL. DR GO; GO:0036092; P:phosphatidylinositol-3-phosphate biosynthetic process; IDA:ComplexPortal. DR GO; GO:1901098; P:positive regulation of autophagosome maturation; TAS:ParkinsonsUK-UCL. DR GO; GO:0032801; P:receptor catabolic process; IMP:UniProtKB. DR GO; GO:0010506; P:regulation of autophagy; IDA:ComplexPortal. DR GO; GO:0032465; P:regulation of cytokinesis; IMP:UniProtKB. DR GO; GO:0071900; P:regulation of protein serine/threonine kinase activity; IDA:UniProtKB. DR GO; GO:0006890; P:retrograde vesicle-mediated transport, Golgi to endoplasmic reticulum; IMP:CACAO. DR GO; GO:0035493; P:SNARE complex assembly; IBA:GO_Central. DR GO; GO:0007051; P:spindle organization; IEA:Ensembl. DR GO; GO:0046718; P:symbiont entry into host cell; IEA:Ensembl. DR CDD; cd00030; C2; 1. DR FunFam; 2.60.40.150:FF:000148; UV radiation resistance associated gene; 1. DR Gene3D; 2.60.40.150; C2 domain; 1. DR InterPro; IPR000008; C2_dom. DR InterPro; IPR035892; C2_domain_sf. DR InterPro; IPR018791; UV_resistance/autophagy_Atg14. DR PANTHER; PTHR15157; UV RADIATION RESISTANCE-ASSOCIATED GENE PROTEIN; 1. DR PANTHER; PTHR15157:SF5; UV RADIATION RESISTANCE-ASSOCIATED GENE PROTEIN; 1. DR Pfam; PF10186; ATG14; 1. DR Pfam; PF00168; C2; 1. DR SMART; SM00239; C2; 1. DR SUPFAM; SSF49562; C2 domain (Calcium/lipid-binding domain, CaLB); 1. DR PROSITE; PS50004; C2; 1. PE 1: Evidence at protein level; KW 3D-structure; Alternative splicing; Centromere; Chromosome; Coiled coil; KW Cytoplasmic vesicle; DNA damage; DNA repair; Endoplasmic reticulum; KW Endosome; Lysosome; Phosphoprotein; Proteomics identification; KW Reference proteome. FT CHAIN 1..699 FT /note="UV radiation resistance-associated gene protein" FT /id="PRO_0000065750" FT DOMAIN 23..149 FT /note="C2" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041" FT REGION 1..24 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 200..269 FT /note="Sufficient for interaction with STX7; VTI1B AND FT STX8" FT /evidence="ECO:0000269|PubMed:24550300" FT REGION 270..442 FT /note="Sufficient for interaction with VPS16, required for FT interaction with CEP63" FT /evidence="ECO:0000269|PubMed:18552835, FT ECO:0000269|PubMed:22542840" FT REGION 443..699 FT /note="Required for interaction with PRKDC, XRCC6 and FT XRCC5" FT /evidence="ECO:0000269|PubMed:22542840" FT REGION 486..591 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COILED 224..305 FT /evidence="ECO:0000255" FT COMPBIAS 1..10 FT /note="Low complexity" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 523..535 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 545..556 FT /note="Low complexity" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 557..567 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT MOD_RES 493 FT /note="Phosphoserine" FT /evidence="ECO:0000269|PubMed:25533187" FT MOD_RES 498 FT /note="Phosphoserine; by MTOR" FT /evidence="ECO:0000269|PubMed:25533187, FT ECO:0007744|PubMed:18691976, ECO:0007744|PubMed:19369195, FT ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:23186163" FT MOD_RES 508 FT /note="Phosphoserine" FT /evidence="ECO:0000269|PubMed:25533187" FT MOD_RES 518 FT /note="Phosphothreonine" FT /evidence="ECO:0007744|PubMed:18669648, FT ECO:0007744|PubMed:19690332, ECO:0007744|PubMed:23186163" FT MOD_RES 522 FT /note="Phosphoserine" FT /evidence="ECO:0000269|PubMed:25533187" FT MOD_RES 549 FT /note="Phosphoserine" FT /evidence="ECO:0000269|PubMed:25533187" FT MOD_RES 550 FT /note="Phosphoserine" FT /evidence="ECO:0000269|PubMed:25533187, FT ECO:0007744|PubMed:23186163" FT MOD_RES 571 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:19369195" FT MOD_RES 582 FT /note="Phosphoserine" FT /evidence="ECO:0000269|PubMed:25533187" FT MOD_RES 689 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163" FT VAR_SEQ 1..372 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_056176" FT VARIANT 10 FT /note="P -> H (in dbSNP:rs7118567)" FT /id="VAR_059737" FT MUTAGEN 498 FT /note="S->A: Abolishes phosphorylation by MTOR, decreases FT interaction with RUBCN, increases interaction with VPS16 FT and VPS39, promotes autophagosome maturation and FT endosome-lysosomal degradation of EGFR." FT /evidence="ECO:0000269|PubMed:25533187" SQ SEQUENCE 699 AA; 78151 MW; 23C4413B10F641BA CRC64; MSASASVGGP VPQPPPGPAA ALPPGSAARA LHVELPSQQR RLRHLRNIAA RNIVNRNGHQ LLDTYFTLHL CSTEKIYKEF YRSEVIKNSL NPTWRSLDFG IMPDRLDTSV SCFVVKIWGG KENIYQLLIE WKVCLDGLKY LGQQIHARNQ NEIIFGLNDG YYGAPFEHKG YSNAQKTILL QVDQNCVRNS YDVFSLLRLH RAQCAIKQTQ VTVQKIGKEI EEKLRLTSTS NELKKKSECL QLKILVLQNE LERQKKALGR EVALLHKQQI ALQDKGSAFS AEHLKLQLQK ESLNELRKEC TAKRELFLKT NAQLTIRCRQ LLSELSYIYP IDLNEHKDYF VCGVKLPNSE DFQAKDDGSI AVALGYTAHL VSMISFFLQV PLRYPIIHKG SRSTIKDNIN DKLTEKEREF PLYPKGGEKL QFDYGVYLLN KNIAQLRYQH GLGTPDLRQT LPNLKNFMEH GLMVRCDRHH TSSAIPVPKR QSSIFGGADV GFSGGIPSPD KGHRKRASSE NERLQYKTPP PSYNSALAQP VTTVPSMGET ERKITSLSSS LDTSLDFSKE NKKKGEDLVG SLNGGHANVH PSQEQGEALS GHRATVNGTL LPSEQAGSAS VQLPGEFHPV SEAELCCTVE QAEEIIGLEA TGFASGDQLE AFNCIPVDSA VAVECDEQVL GEFEEFSRRI YALNENVSSF RRPRRSSDK //