UVRAG_MOUSE
ID UVRAG_MOUSE Reviewed; 698 AA.
AC Q8K245; Q8BVI8; Q8C0K8;
DT 24-JUN-2015, integrated into UniProtKB/Swiss-Prot.
DT 24-JUN-2015, sequence version 2.
DT 03-AUG-2022, entry version 116.
DE RecName: Full=UV radiation resistance-associated protein;
GN Name=Uvrag; Synonyms=Uvrag1;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090 {ECO:0000312|EMBL:AAH34176.1};
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J, and NOD;
RC TISSUE=Dendritic cell, Medulla oblongata, and Thymus;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=C57BL/6J;
RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of the
RT mouse.";
RL PLoS Biol. 7:E1000112-E1000112(2009).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=FVB/N;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [4]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=17242355; DOI=10.1073/pnas.0609836104;
RA Villen J., Beausoleil S.A., Gerber S.A., Gygi S.P.;
RT "Large-scale phosphorylation analysis of mouse liver.";
RL Proc. Natl. Acad. Sci. U.S.A. 104:1488-1493(2007).
RN [5]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19144319; DOI=10.1016/j.immuni.2008.11.006;
RA Trost M., English L., Lemieux S., Courcelles M., Desjardins M.,
RA Thibault P.;
RT "The phagosomal proteome in interferon-gamma-activated macrophages.";
RL Immunity 30:143-154(2009).
RN [6]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-688, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Heart, Kidney, Liver, Pancreas, Spleen, and Testis;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [7]
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).
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). During autophagy acts as regulatory subunit of
CC the alternative PI3K complex II (PI3KC3-C2) that mediates formation of
CC phosphatidylinositol 3-phosphate and is believed to be involved in
CC maturation of autophagosomes and endocytosis. Activates lipid kinase
CC activity of PIK3C3. Involved in the regulation of degradative endocytic
CC trafficking and cytokinesis, and in regulation of ATG9A transport from
CC the Golgi to the autophagosome; the functions seems to implicate its
CC association with PI3KC3-C2. Involved in maturation of autophagosomes
CC and degradative endocytic trafficking independently of BECN1 but
CC depending on its association with a class C Vps complex (possibly the
CC HOPS complex); the association is also proposed to promote
CC autophagosome recruitment and activation of Rab7 and endosome-endosome
CC fusion events. Enhances class C Vps complex (possibly HOPS complex)
CC association with a SNARE complex and promotes fusogenic SNARE complex
CC formation during late endocytic membrane fusion. 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.
CC {ECO:0000250|UniProtKB:Q9P2Y5}.
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). Required for centrosome stability and proper chromosome
CC segregation. {ECO:0000250|UniProtKB:Q9P2Y5}.
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 (By similarity). PI3KC3-C2 can associate with further
CC regulatory subunits such as RUBCN and probably SH3GLB1/Bif-1 (By
CC similarity). Interacts with SH3GLB1; UVRAG bridges the interaction to
CC BECN1 indicative for an association with the PI3K complex PI3KC3-C2 (By
CC similarity). Interacts with RINT1 (By similarity). Associates with the
CC NRZ complex under basal conditions and dissociates from it under
CC autophagy conditions to associate with the PI3K complex; these complex
CC associations seem to be mutually exclusive (By similarity). Interacts
CC with VPS16; VPS11; VPS18; VPS33 (VPS33A or VPS33B) and VPS39;
CC indicative for an association with a class C Vps tethering complex
CC (possibly the HOPS complex) (By similarity). Interacts with RAB7A;
CC RAB7A competes with UVRAG for RUBCN binding (By similarity). Interacts
CC with STX7, VTI1B, STX8 (By similarity). Interacts with PRKDC, XRCC6 and
CC XRCC5; indicative for an association with the DNA-dependent protein
CC kinase complex DNA-PK (By similarity). Interacts with CEP63 (By
CC similarity). Directly interacts with FEZ1 and SCOC; the interaction
CC with SCOC is reduced by amino acid starvation, but the complex is
CC stabilized in the presence of FEZ1 (By similarity). Interacts with
CC BECN1P1/BECN2 (By similarity). Interacts with SLAMF1 (PubMed:22493499).
CC Interacts with RUBCNL/PACER; promoting targeting of UVRAG to
CC autophagosome (By similarity). {ECO:0000250|UniProtKB:Q9P2Y5,
CC ECO:0000269|PubMed:22493499}.
CC -!- SUBCELLULAR LOCATION: Late endosome {ECO:0000250|UniProtKB:Q9P2Y5}.
CC Lysosome {ECO:0000250|UniProtKB:Q9P2Y5}. Cytoplasmic vesicle,
CC autophagosome {ECO:0000250|UniProtKB:Q9P2Y5}. Early endosome
CC {ECO:0000250|UniProtKB:Q9P2Y5}. Endoplasmic reticulum
CC {ECO:0000250|UniProtKB:Q9P2Y5}. Midbody {ECO:0000250|UniProtKB:Q9P2Y5}.
CC Chromosome, centromere {ECO:0000250|UniProtKB:Q9P2Y5}. Note=Colocalizes
CC with RAB9-positive compartments involved in retrograde transport from
CC late endosomes to trans-Golgi network. Colocalization with early
CC endosomes is only partial. Recruited to autophagosome following
CC interaction with RUBCNL/PACER. {ECO:0000250|UniProtKB:Q9P2Y5}.
CC -!- PTM: Phosphorylated at Ser-497 by MTOR under basal conditions;
CC increases the interaction with RUBCN implicated in inhibitory effect of
CC RUBCN on PI3KC3 and decreases interaction with RAB7A, and VPS16 and
CC VPS39 (indicative for a class C Vps complex, possibly the HOPS complex)
CC (By similarity). {ECO:0000250|UniProtKB:Q9P2Y5}.
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DR EMBL; AK030814; BAC27144.1; -; mRNA.
DR EMBL; AK078085; BAC37120.1; -; mRNA.
DR EMBL; AK154903; BAE32914.1; -; mRNA.
DR EMBL; AC093351; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC115850; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC034176; AAH34176.1; -; mRNA.
DR CCDS; CCDS21476.1; -.
DR RefSeq; NP_848750.3; NM_178635.3.
DR PDB; 5YR0; X-ray; 1.90 A; B=228-275.
DR PDBsum; 5YR0; -.
DR AlphaFoldDB; Q8K245; -.
DR SMR; Q8K245; -.
DR ComplexPortal; CPX-76; Phosphatidylinositol 3-kinase complex, class III, UVRAG variant.
DR IntAct; Q8K245; 17.
DR MINT; Q8K245; -.
DR STRING; 10090.ENSMUSP00000045297; -.
DR iPTMnet; Q8K245; -.
DR PhosphoSitePlus; Q8K245; -.
DR EPD; Q8K245; -.
DR jPOST; Q8K245; -.
DR MaxQB; Q8K245; -.
DR PaxDb; Q8K245; -.
DR PRIDE; Q8K245; -.
DR ProteomicsDB; 298259; -.
DR Antibodypedia; 2165; 440 antibodies from 38 providers.
DR DNASU; 78610; -.
DR Ensembl; ENSMUST00000037968; ENSMUSP00000045297; ENSMUSG00000035354.
DR GeneID; 78610; -.
DR KEGG; mmu:78610; -.
DR UCSC; uc009ikz.2; mouse.
DR CTD; 7405; -.
DR MGI; MGI:1925860; Uvrag.
DR VEuPathDB; HostDB:ENSMUSG00000035354; -.
DR eggNOG; KOG2896; Eukaryota.
DR GeneTree; ENSGT00390000012877; -.
DR OMA; XELFLKT; -.
DR OrthoDB; 1081121at2759; -.
DR PhylomeDB; Q8K245; -.
DR TreeFam; TF323546; -.
DR Reactome; R-MMU-1632852; Macroautophagy.
DR BioGRID-ORCS; 78610; 8 hits in 109 CRISPR screens.
DR ChiTaRS; Uvrag; mouse.
DR PRO; PR:Q8K245; -.
DR Proteomes; UP000000589; Chromosome 7.
DR RNAct; Q8K245; protein.
DR Bgee; ENSMUSG00000035354; Expressed in gastrula and 258 other tissues.
DR ExpressionAtlas; Q8K245; baseline and differential.
DR GO; GO:0000421; C:autophagosome membrane; ISS:UniProtKB.
DR GO; GO:0005813; C:centrosome; ISO:MGI.
DR GO; GO:0000775; C:chromosome, centromeric region; IEA:UniProtKB-SubCell.
DR GO; GO:0070418; C:DNA-dependent protein kinase complex; ISO:MGI.
DR GO; GO:0005769; C:early endosome; ISO:MGI.
DR GO; GO:0005783; C:endoplasmic reticulum; ISO:MGI.
DR GO; GO:0005768; C:endosome; IBA:GO_Central.
DR GO; GO:0005770; C:late endosome; ISO:MGI.
DR GO; GO:0005764; C:lysosome; ISO:MGI.
DR GO; GO:0000323; C:lytic vacuole; IBA:GO_Central.
DR GO; GO:0030496; C:midbody; ISO:MGI.
DR GO; GO:0045335; C:phagocytic vesicle; IPI:MGI.
DR GO; GO:0035032; C:phosphatidylinositol 3-kinase complex, class III; ISO:MGI.
DR GO; GO:0032991; C:protein-containing complex; IDA:MGI.
DR GO; GO:0017124; F:SH3 domain binding; IPI:MGI.
DR GO; GO:0000149; F:SNARE binding; IDA:MGI.
DR GO; GO:0097352; P:autophagosome maturation; ISS:UniProtKB.
DR GO; GO:0006914; P:autophagy; ISO:MGI.
DR GO; GO:0007098; P:centrosome cycle; IMP:UniProtKB.
DR GO; GO:0007059; P:chromosome segregation; IMP:UniProtKB.
DR GO; GO:0006281; P:DNA repair; IMP:UniProtKB.
DR GO; GO:0097680; P:double-strand break repair via classical nonhomologous end joining; ISO:MGI.
DR GO; GO:0051684; P:maintenance of Golgi location; ISO:MGI.
DR GO; GO:0036092; P:phosphatidylinositol-3-phosphate biosynthetic process; ISO:MGI.
DR GO; GO:0006468; P:protein phosphorylation; ISO:MGI.
DR GO; GO:0032801; P:receptor catabolic process; ISO:MGI.
DR GO; GO:0010506; P:regulation of autophagy; ISO:MGI.
DR GO; GO:0032465; P:regulation of cytokinesis; ISO:MGI.
DR GO; GO:0071900; P:regulation of protein serine/threonine kinase activity; ISO:MGI.
DR GO; GO:0006890; P:retrograde vesicle-mediated transport, Golgi to endoplasmic reticulum; ISO:MGI.
DR GO; GO:0035493; P:SNARE complex assembly; IMP:MGI.
DR GO; GO:0007051; P:spindle organization; IMP:UniProtKB.
DR GO; GO:0046718; P:viral entry into host cell; IMP:MGI.
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 SUPFAM; SSF49562; SSF49562; 1.
DR PROSITE; PS50004; C2; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Centromere; Chromosome; Coiled coil; Cytoplasmic vesicle;
KW DNA damage; DNA repair; Endoplasmic reticulum; Endosome; Lysosome;
KW Phosphoprotein; Reference proteome.
FT CHAIN 1..698
FT /note="UV radiation resistance-associated protein"
FT /id="PRO_0000433403"
FT DOMAIN 23..149
FT /note="C2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT REGION 1..21
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 199..268
FT /note="Sufficient for interaction with STX7; VTI1B AND
FT STX8"
FT /evidence="ECO:0000250|UniProtKB:Q9P2Y5"
FT REGION 269..441
FT /note="Sufficient for interaction with VPS16, required for
FT interaction with CEP63"
FT /evidence="ECO:0000250|UniProtKB:Q9P2Y5"
FT REGION 442..698
FT /note="Required for interaction with PRKDC, XRCC6 and
FT XRCC5"
FT /evidence="ECO:0000250|UniProtKB:Q9P2Y5"
FT REGION 477..551
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 565..586
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COILED 200..304
FT /evidence="ECO:0000255"
FT COMPBIAS 512..534
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 492
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9P2Y5"
FT MOD_RES 497
FT /note="Phosphoserine; by MTOR"
FT /evidence="ECO:0000250|UniProtKB:Q9P2Y5"
FT MOD_RES 507
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9P2Y5"
FT MOD_RES 517
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q9P2Y5"
FT MOD_RES 521
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9P2Y5"
FT MOD_RES 548
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9P2Y5"
FT MOD_RES 549
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9P2Y5"
FT MOD_RES 570
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9P2Y5"
FT MOD_RES 688
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT CONFLICT 335
FT /note="N -> H (in Ref. 3; AAH34176)"
FT /evidence="ECO:0000305"
FT CONFLICT 355
FT /note="D -> E (in Ref. 3; AAH34176)"
FT /evidence="ECO:0000305"
FT CONFLICT 497
FT /note="S -> T (in Ref. 1; BAC37120)"
FT /evidence="ECO:0000305"
FT HELIX 232..273
FT /evidence="ECO:0007829|PDB:5YR0"
SQ SEQUENCE 698 AA; 77525 MW; 245A411198286F33 CRC64;
MSSCASLGGP VPLPPPGPSA ALTSGAPARA LHVELPSQQR RLRHLRNIAA RNIVNRNGHQ
LLDTYFTLHL CDNEKIFKEF YRSEVIKNSL NPTWRSLDFG IMPDRLDTSV SCFVVKIWGG
KEEAFQLLIE WKVYLDGLKY LGQQIHARNQ NEIIFGLNDG YYGAPCEHKG HPNAQKNLLQ
VDQNCVRNSY DVFSLLRLHR AQCAIKQTQV TVQRLGKEIE EKLRLTSTSN ELKKESECLR
LKILVLRNEL ERQKKALGRE VAFLHKQQMA LQDKGSAFST EHGKLQLQKD SLSELRKECT
AKRELFLKTN AQLTIRCRQL LSELSYIYPI DLNENKDYFV CGVKLPNSED FQAKDDGSIA
VALGYTAHLV SMISFFLQVP LRYPIIHKGS RSTIKDNIND KLTEKEREFP LYPKGGEKLQ
FDYGVYLLNK NIAQLRYQHG LGTPDLRQTL PNLKNFMEHG LMVRCDRHHI SNAIPVPKRQ
SSTFGGADGG FSAGIPSPDK VHRKRASSEN ERLQYKTPPP SYNSALTQPG VAMPTSGDSE
RKVAPLSSSL DTSLDFSKEN KKAGVDLGSS VSGDHGNSDS GQEQGEALPG HLAAVNGTAL
PSEQAGPAGT LLPGSCHPAP SAELCCAVEQ AEEIIGLEAT GFTSGDQLEA LSCIPVDSAV
AVECDEQVLG EFEEFSRRIY ALSENVSSFR RPRRSSDK
