UVRAG_HUMAN
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 03-AUG-2022, entry version 165.
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 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 regulatory subunit of the alternative PI3K complex II (PI3KC3-
CC C2) that mediates formation of phosphatidylinositol 3-phosphate and is
CC 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:25533187, PubMed:20974968). 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 {ECO:0000269|PubMed:16799551, ECO:0000269|PubMed:17891140,
CC ECO:0000269|PubMed:18552835, ECO:0000269|PubMed:18843052,
CC ECO:0000269|PubMed:19050071, ECO:0000269|PubMed:19270696,
CC ECO:0000269|PubMed:20643123, ECO:0000269|PubMed:20974968,
CC ECO:0000269|PubMed:22354037, ECO:0000269|PubMed:22493499,
CC ECO:0000269|PubMed:22542840, ECO:0000269|PubMed:23878393,
CC ECO:0000269|PubMed:23954414, ECO:0000269|PubMed:24056303,
CC ECO:0000269|PubMed:24550300, ECO:0000269|PubMed:25533187,
CC ECO:0000269|PubMed:28306502}.
CC -!- INTERACTION:
CC Q9P2Y5; Q07812: BAX; NbExp=6; IntAct=EBI-2952704, EBI-516580;
CC Q9P2Y5; Q14457: BECN1; NbExp=45; IntAct=EBI-2952704, EBI-949378;
CC Q9P2Y5; Q8NEB9: PIK3C3; NbExp=23; IntAct=EBI-2952704, EBI-1056470;
CC Q9P2Y5; Q6NUQ1: RINT1; NbExp=18; IntAct=EBI-2952704, EBI-726876;
CC Q9P2Y5; Q92622: RUBCN; NbExp=9; 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; 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};
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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 PDB; 7BL1; EM; 9.80 A; AAA=1-699.
DR PDBsum; 7BL1; -.
DR AlphaFoldDB; Q9P2Y5; -.
DR SMR; Q9P2Y5; -.
DR BioGRID; 113248; 48.
DR ComplexPortal; CPX-74; Phosphatidylinositol 3-kinase complex, class III, UVRAG variant.
DR CORUM; Q9P2Y5; -.
DR DIP; DIP-48652N; -.
DR IntAct; Q9P2Y5; 59.
DR MINT; Q9P2Y5; -.
DR STRING; 9606.ENSP00000348455; -.
DR ChEMBL; CHEMBL4296018; -.
DR iPTMnet; Q9P2Y5; -.
DR PhosphoSitePlus; Q9P2Y5; -.
DR BioMuta; UVRAG; -.
DR DMDM; 20140879; -.
DR EPD; Q9P2Y5; -.
DR jPOST; Q9P2Y5; -.
DR MassIVE; Q9P2Y5; -.
DR MaxQB; Q9P2Y5; -.
DR PaxDb; Q9P2Y5; -.
DR PeptideAtlas; Q9P2Y5; -.
DR PRIDE; Q9P2Y5; -.
DR ProteomicsDB; 3674; -.
DR ProteomicsDB; 83914; -. [Q9P2Y5-1]
DR Antibodypedia; 2165; 440 antibodies from 38 providers.
DR DNASU; 7405; -.
DR Ensembl; ENST00000356136.8; ENSP00000348455.3; ENSG00000198382.9. [Q9P2Y5-1]
DR Ensembl; ENST00000531818.5; ENSP00000434082.1; ENSG00000198382.9. [Q9P2Y5-2]
DR Ensembl; ENST00000532130.1; ENSP00000436270.1; ENSG00000198382.9. [Q9P2Y5-2]
DR Ensembl; ENST00000533454.5; ENSP00000431256.1; ENSG00000198382.9. [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 CTD; 7405; -.
DR DisGeNET; 7405; -.
DR GeneCards; UVRAG; -.
DR HGNC; HGNC:12640; UVRAG.
DR HPA; ENSG00000198382; Low tissue specificity.
DR MIM; 602493; gene.
DR neXtProt; NX_Q9P2Y5; -.
DR OpenTargets; ENSG00000198382; -.
DR PharmGKB; PA37264; -.
DR VEuPathDB; HostDB:ENSG00000198382; -.
DR eggNOG; KOG2896; Eukaryota.
DR GeneTree; ENSGT00390000012877; -.
DR HOGENOM; CLU_009375_2_0_1; -.
DR InParanoid; Q9P2Y5; -.
DR OMA; XELFLKT; -.
DR OrthoDB; 1081121at2759; -.
DR PhylomeDB; Q9P2Y5; -.
DR TreeFam; TF323546; -.
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 BioGRID-ORCS; 7405; 91 hits in 1086 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 196 other tissues.
DR ExpressionAtlas; Q9P2Y5; baseline and differential.
DR Genevisible; Q9P2Y5; HS.
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: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:0006468; P:protein phosphorylation; IDA:ComplexPortal.
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:viral entry into host cell; IEA:Ensembl.
DR Gene3D; 2.60.40.150; -; 1.
DR InterPro; IPR000008; C2_dom.
DR InterPro; IPR035892; C2_domain_sf.
DR InterPro; IPR018791; UV_resistance/autophagy_Atg14.
DR Pfam; PF10186; ATG14; 1.
DR SMART; SM00239; C2; 1.
DR SUPFAM; SSF49562; SSF49562; 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; 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 513..555
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 576..591
FT /note="Polar 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 endosome-
FT 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
