VRK3_MOUSE
ID VRK3_MOUSE Reviewed; 453 AA.
AC Q8K3G5; Q921W6;
DT 10-OCT-2003, integrated into UniProtKB/Swiss-Prot.
DT 10-OCT-2003, sequence version 2.
DT 03-AUG-2022, entry version 154.
DE RecName: Full=Inactive serine/threonine-protein kinase VRK3;
DE AltName: Full=Serine/threonine-protein pseudokinase VRK3;
DE AltName: Full=Vaccinia-related kinase 3;
GN Name=Vrk3;
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;
RN [1]
RP NUCLEOTIDE SEQUENCE.
RX PubMed=11986327; DOI=10.1074/jbc.m202833200;
RA Angata T., Kerr S.C., Greaves D.R., Varki N.M., Crocker P.R., Varki A.;
RT "Cloning and characterization of human Siglec-11. A recently evolved
RT signaling molecule that can interact with SHP-1 and SHP-2 and is expressed
RT by tissue macrophages, including brain microglia.";
RL J. Biol. Chem. 277:24466-24474(2002).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Colon, Liver, and Mammary tumor;
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 [3]
RP TISSUE SPECIFICITY, AND DEVELOPMENTAL STAGE.
RX PubMed=12782311; DOI=10.1016/s0014-5793(03)00501-5;
RA Vega F.M., Gonzalo P., Gaspar M.L., Lazo P.A.;
RT "Expression of the VRK (vaccinia-related kinase) gene family of p53
RT regulators in murine hematopoietic development.";
RL FEBS Lett. 544:176-180(2003).
RN [4]
RP FUNCTION, SUBCELLULAR LOCATION, AND NUCLEAR LOCALIZATION SIGNAL.
RX PubMed=14645249; DOI=10.1074/jbc.m310813200;
RA Nichols R.J., Traktman P.;
RT "Characterization of three paralogous members of the Mammalian vaccinia
RT related kinase family.";
RL J. Biol. Chem. 279:7934-7946(2004).
RN [5]
RP FUNCTION, AND INTERACTION WITH DUSP3.
RX PubMed=16845380; DOI=10.1038/ncb1447;
RA Kang T.H., Kim K.T.;
RT "Negative regulation of ERK activity by VRK3-mediated activation of VHR
RT phosphatase.";
RL Nat. Cell Biol. 8:863-869(2006).
RN [6]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-59, AND IDENTIFICATION BY
RP 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 [7]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-59, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Lung, 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).
CC -!- FUNCTION: Inactive kinase that suppresses ERK activity by promoting
CC phosphatase activity of DUSP3 which specifically dephosphorylates and
CC inactivates ERK in the nucleus. {ECO:0000269|PubMed:14645249,
CC ECO:0000269|PubMed:16845380}.
CC -!- SUBUNIT: Interacts with DUSP3. Interacts with RAN (By similarity).
CC {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:14645249}.
CC -!- TISSUE SPECIFICITY: Expressed in liver, kidney, muscle, thymus, and
CC bone marrow. Weakly expressed in spleen. {ECO:0000269|PubMed:12782311}.
CC -!- DEVELOPMENTAL STAGE: Weakly expressed in embryo compared to VRK1 and
CC VRK3. Expressed from 10.5 dpc to 13.5 dpc in developing liver and then
CC decreases. It increases again from 17.5 dpc and remains thereafter.
CC Highly expressed in hematopoietic embryonic tissues from 10.5 dpc to
CC 14.5 dpc. Strongly expressed in the yolk-sac.
CC {ECO:0000269|PubMed:12782311}.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. CK1 Ser/Thr
CC protein kinase family. VRK subfamily. {ECO:0000305}.
CC -!- CAUTION: Inactive as a kinase due to its inability to bind ATP.
CC {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; AY115107; AAM74471.1; -; Genomic_DNA.
DR EMBL; BC010473; AAH10473.1; -; mRNA.
DR EMBL; BC024782; AAH24782.1; -; mRNA.
DR EMBL; BC024839; AAH24839.1; -; mRNA.
DR EMBL; BC034196; AAH34196.1; -; mRNA.
DR CCDS; CCDS21214.1; -.
DR RefSeq; NP_598706.1; NM_133945.1.
DR RefSeq; XP_006540601.1; XM_006540538.3.
DR AlphaFoldDB; Q8K3G5; -.
DR SMR; Q8K3G5; -.
DR BioGRID; 221691; 3.
DR IntAct; Q8K3G5; 1.
DR STRING; 10090.ENSMUSP00000002275; -.
DR iPTMnet; Q8K3G5; -.
DR PhosphoSitePlus; Q8K3G5; -.
DR EPD; Q8K3G5; -.
DR jPOST; Q8K3G5; -.
DR MaxQB; Q8K3G5; -.
DR PaxDb; Q8K3G5; -.
DR PRIDE; Q8K3G5; -.
DR ProteomicsDB; 275190; -.
DR Antibodypedia; 18806; 95 antibodies from 26 providers.
DR DNASU; 101568; -.
DR Ensembl; ENSMUST00000002275; ENSMUSP00000002275; ENSMUSG00000002205.
DR GeneID; 101568; -.
DR KEGG; mmu:101568; -.
DR UCSC; uc009gqr.1; mouse.
DR CTD; 51231; -.
DR MGI; MGI:2182465; Vrk3.
DR VEuPathDB; HostDB:ENSMUSG00000002205; -.
DR eggNOG; KOG1164; Eukaryota.
DR GeneTree; ENSGT00940000158111; -.
DR HOGENOM; CLU_019279_4_4_1; -.
DR InParanoid; Q8K3G5; -.
DR OMA; AYMEGSR; -.
DR OrthoDB; 866200at2759; -.
DR PhylomeDB; Q8K3G5; -.
DR TreeFam; TF106473; -.
DR Reactome; R-MMU-202670; ERKs are inactivated.
DR BioGRID-ORCS; 101568; 4 hits in 74 CRISPR screens.
DR PRO; PR:Q8K3G5; -.
DR Proteomes; UP000000589; Chromosome 7.
DR RNAct; Q8K3G5; protein.
DR Bgee; ENSMUSG00000002205; Expressed in seminiferous tubule of testis and 258 other tissues.
DR ExpressionAtlas; Q8K3G5; baseline and differential.
DR Genevisible; Q8K3G5; MM.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0043231; C:intracellular membrane-bounded organelle; ISO:MGI.
DR GO; GO:0005730; C:nucleolus; ISO:MGI.
DR GO; GO:0005654; C:nucleoplasm; ISO:MGI.
DR GO; GO:0005634; C:nucleus; IDA:MGI.
DR GO; GO:0005524; F:ATP binding; IEA:InterPro.
DR GO; GO:0019903; F:protein phosphatase binding; IPI:MGI.
DR GO; GO:0004674; F:protein serine/threonine kinase activity; IBA:GO_Central.
DR GO; GO:0016572; P:histone phosphorylation; IBA:GO_Central.
DR GO; GO:0070373; P:negative regulation of ERK1 and ERK2 cascade; IDA:MGI.
DR GO; GO:0018105; P:peptidyl-serine phosphorylation; IBA:GO_Central.
DR GO; GO:0032516; P:positive regulation of phosphoprotein phosphatase activity; IPI:MGI.
DR GO; GO:0007165; P:signal transduction; IBA:GO_Central.
DR GO; GO:0007519; P:skeletal muscle tissue development; ISO:MGI.
DR InterPro; IPR011009; Kinase-like_dom_sf.
DR InterPro; IPR000719; Prot_kinase_dom.
DR InterPro; IPR026870; Zinc_ribbon_dom.
DR Pfam; PF00069; Pkinase; 1.
DR Pfam; PF13240; zinc_ribbon_2; 1.
DR SMART; SM00220; S_TKc; 1.
DR SUPFAM; SSF56112; SSF56112; 1.
DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 1.
PE 1: Evidence at protein level;
KW Nucleotide-binding; Nucleus; Phosphoprotein; Reference proteome.
FT CHAIN 1..453
FT /note="Inactive serine/threonine-protein kinase VRK3"
FT /id="PRO_0000086809"
FT DOMAIN 125..436
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT REGION 30..123
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 49..64
FT /note="Nuclear localization signal"
FT /evidence="ECO:0000269|PubMed:14645249"
FT COMPBIAS 36..123
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 54
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q8IV63"
FT MOD_RES 55
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q8IV63"
FT MOD_RES 59
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:17242355,
FT ECO:0007744|PubMed:21183079"
FT MOD_RES 82
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q8IV63"
FT MOD_RES 83
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q8IV63"
FT CONFLICT 44
FT /note="S -> P (in Ref. 1; AAM74471)"
FT /evidence="ECO:0000305"
FT CONFLICT 168
FT /note="V -> I (in Ref. 1; AAM74471)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 453 AA; 50830 MW; B882A3F60802C432 CRC64;
MISFCPVCGK SVKVSFKFCP YCGKALPVEE DGGTQSAVTP HVSSVPGSRR DLNSSFETSP
KKVKCSHTVT SLPLSRHSDC DSSGSDNTLT SPDRATGTRS RPLTPKGSPL SNRQSPQTLK
RTRVTTSLQA LATGTELTDQ NGKHWTLGAL QIRDDQGILY EAEPTSAVPS ESRTQKWRFS
LKLDSKDGRL FNEQNFFQRV AKPLQVNKWK KQFLLPLLAI PTCIGFGIHQ DKYRFLVFPS
LGRSLQSALD DNPKHVVSER CVLQVACRLL DALEYLHENE YVHGNLTAEN VFVNPEDLSQ
VTLVGYGFTY RYCPGGKHVA YKEGSRSPHD GDLEFISMDL HKGCGPSRRS DLQTLGYCML
KWLYGSLPWT NCLPNTEKIT RQKQKYLDSP ERLVGLCGRW NKASETLREY LKVVMALNYE
EKPPYATLRN SLEALLQDMR VSPYDPLDLQ MVP