ID   VRK3_HUMAN              Reviewed;         474 AA.
AC   Q8IV63; A6NEG5; A8KA53; Q502Y2; Q9P2V8;
DT   10-OCT-2003, integrated into UniProtKB/Swiss-Prot.
DT   10-OCT-2003, sequence version 2.
DT   27-MAR-2024, entry version 186.
DE   RecName: Full=Serine/threonine-protein kinase VRK3;
DE            EC=2.7.11.22;
DE   AltName: Full=Vaccinia-related kinase 3;
GN   Name=VRK3;
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 [MRNA] (ISOFORM 1).
RC   TISSUE=Liver;
RA   Nezu J.;
RT   "Vaccinia related kinase 3 (VRK3).";
RL   Submitted (AUG-1999) to the EMBL/GenBank/DDBJ databases.
RN   [2]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RA   Ni X., Xie Y., Mao Y.;
RT   "Cloning and characterization of a novel human VRK3 gene.";
RL   Submitted (MAY-2002) to the EMBL/GenBank/DDBJ databases.
RN   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 3).
RC   TISSUE=Testis, and Trachea;
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=15057824; DOI=10.1038/nature02399;
RA   Grimwood J., Gordon L.A., Olsen A.S., Terry A., Schmutz J., Lamerdin J.E.,
RA   Hellsten U., Goodstein D., Couronne O., Tran-Gyamfi M., Aerts A.,
RA   Altherr M., Ashworth L., Bajorek E., Black S., Branscomb E., Caenepeel S.,
RA   Carrano A.V., Caoile C., Chan Y.M., Christensen M., Cleland C.A.,
RA   Copeland A., Dalin E., Dehal P., Denys M., Detter J.C., Escobar J.,
RA   Flowers D., Fotopulos D., Garcia C., Georgescu A.M., Glavina T., Gomez M.,
RA   Gonzales E., Groza M., Hammon N., Hawkins T., Haydu L., Ho I., Huang W.,
RA   Israni S., Jett J., Kadner K., Kimball H., Kobayashi A., Larionov V.,
RA   Leem S.-H., Lopez F., Lou Y., Lowry S., Malfatti S., Martinez D.,
RA   McCready P.M., Medina C., Morgan J., Nelson K., Nolan M., Ovcharenko I.,
RA   Pitluck S., Pollard M., Popkie A.P., Predki P., Quan G., Ramirez L.,
RA   Rash S., Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A.,
RA   She X., Smith D., Slezak T., Solovyev V., Thayer N., Tice H., Tsai M.,
RA   Ustaszewska A., Vo N., Wagner M., Wheeler J., Wu K., Xie G., Yang J.,
RA   Dubchak I., Furey T.S., DeJong P., Dickson M., Gordon D., Eichler E.E.,
RA   Pennacchio L.A., Richardson P., Stubbs L., Rokhsar D.S., Myers R.M.,
RA   Rubin E.M., Lucas S.M.;
RT   "The DNA sequence and biology of human chromosome 19.";
RL   Nature 428:529-535(2004).
RN   [5]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC   TISSUE=Brain, and Skin;
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   [6]
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   [7]
RP   INTERACTION WITH RAN.
RX   PubMed=18617507; DOI=10.1074/mcp.m700586-mcp200;
RA   Sanz-Garcia M., Lopez-Sanchez I., Lazo P.A.;
RT   "Proteomics identification of nuclear Ran GTPase as an inhibitor of human
RT   VRK1 and VRK2 (vaccinia-related kinase) activities.";
RL   Mol. Cell. Proteomics 7:2199-2214(2008).
RN   [8]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-55 AND SER-59, AND
RP   IDENTIFICATION BY 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   [9]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-82; SER-83 AND SER-90, AND
RP   IDENTIFICATION BY 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   [10]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-82 AND SER-83, AND
RP   IDENTIFICATION BY 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   [11]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-82; SER-83; SER-115 AND
RP   SER-122, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX   PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA   Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T.,
RA   Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.;
RT   "System-wide temporal characterization of the proteome and phosphoproteome
RT   of human embryonic stem cell differentiation.";
RL   Sci. Signal. 4:RS3-RS3(2011).
RN   [12]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-54; SER-59 AND SER-83, AND
RP   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   [13]
RP   FUNCTION, MUTAGENESIS OF LYS-203, AND CATALYTIC ACTIVITY.
RX   PubMed=25899223; DOI=10.1016/j.bbamcr.2015.04.007;
RA   Park C.H., Ryu H.G., Kim S.H., Lee D., Song H., Kim K.T.;
RT   "Presumed pseudokinase VRK3 functions as a BAF kinase.";
RL   Biochim. Biophys. Acta 1853:1738-1748(2015).
RN   [14]
RP   FUNCTION, PHOSPHORYLATION AT SER-108, SUBCELLULAR LOCATION, MUTAGENESIS OF
RP   SER-108, AND INTERACTION WITH DUSP3.
RX   PubMed=27346674; DOI=10.1038/srep28634;
RA   Song H., Kim W., Choi J.H., Kim S.H., Lee D., Park C.H., Kim S., Kim D.Y.,
RA   Kim K.T.;
RT   "Stress-induced nuclear translocation of CDK5 suppresses neuronal death by
RT   downregulating ERK activation via VRK3 phosphorylation.";
RL   Sci. Rep. 6:28634-28634(2016).
RN   [15]
RP   FUNCTION, AND INTERACTION WITH HSP70/HSPA1A AND DUSP3.
RX   PubMed=27941812; DOI=10.1038/srep38452;
RA   Song H., Kim W., Kim S.H., Kim K.T.;
RT   "VRK3-mediated nuclear localization of HSP70 prevents glutamate
RT   excitotoxicity-induced apoptosis and Abeta accumulation via enhancement of
RT   ERK phosphatase VHR activity.";
RL   Sci. Rep. 6:38452-38452(2016).
RN   [16]
RP   UBIQUITINATION BY RNF144A, AND SUBCELLULAR LOCATION.
RX   PubMed=33067254; DOI=10.1242/jcs.247304;
RA   Han S.H., Kim K.T.;
RT   "RNF144a induces ERK-dependent cell death under oxidative stress via
RT   downregulation of vaccinia-related kinase 3.";
RL   J. Cell Sci. 133:0-0(2020).
RN   [17]
RP   X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 146-474, FUNCTION, AND LACK OF
RP   CATALYTIC ACTIVITY.
RX   PubMed=19141289; DOI=10.1016/j.str.2008.10.018;
RA   Scheeff E.D., Eswaran J., Bunkoczi G., Knapp S., Manning G.;
RT   "Structure of the pseudokinase VRK3 reveals a degraded catalytic site, a
RT   highly conserved kinase fold, and a putative regulatory binding site.";
RL   Structure 17:128-138(2009).
RN   [18]
RP   VARIANTS [LARGE SCALE ANALYSIS] PHE-59; THR-105; LEU-171; LEU-268; TYR-288;
RP   CYS-370 AND GLY-371.
RX   PubMed=17344846; DOI=10.1038/nature05610;
RA   Greenman C., Stephens P., Smith R., Dalgliesh G.L., Hunter C., Bignell G.,
RA   Davies H., Teague J., Butler A., Stevens C., Edkins S., O'Meara S.,
RA   Vastrik I., Schmidt E.E., Avis T., Barthorpe S., Bhamra G., Buck G.,
RA   Choudhury B., Clements J., Cole J., Dicks E., Forbes S., Gray K.,
RA   Halliday K., Harrison R., Hills K., Hinton J., Jenkinson A., Jones D.,
RA   Menzies A., Mironenko T., Perry J., Raine K., Richardson D., Shepherd R.,
RA   Small A., Tofts C., Varian J., Webb T., West S., Widaa S., Yates A.,
RA   Cahill D.P., Louis D.N., Goldstraw P., Nicholson A.G., Brasseur F.,
RA   Looijenga L., Weber B.L., Chiew Y.-E., DeFazio A., Greaves M.F.,
RA   Green A.R., Campbell P., Birney E., Easton D.F., Chenevix-Trench G.,
RA   Tan M.-H., Khoo S.K., Teh B.T., Yuen S.T., Leung S.Y., Wooster R.,
RA   Futreal P.A., Stratton M.R.;
RT   "Patterns of somatic mutation in human cancer genomes.";
RL   Nature 446:153-158(2007).
CC   -!- FUNCTION: Plays a role in the regulation of the cell cycle by
CC       phosphorylating the nuclear envelope protein barrier-to-autointegration
CC       factor/BAF that is required for disassembly and reassembly,
CC       respectively, of the nuclear envelope during mitosis (PubMed:25899223).
CC       Under normal physiological conditions, negatively regulates ERK
CC       activity along with VHR/DUSP3 phosphatase in the nucleus, causing
CC       timely and transient action of ERK. Stress conditions activate CDK5
CC       which phosphorylates VRK3 to increase VHR phosphatase activity and
CC       suppress prolonged ERK activation that causes cell death
CC       (PubMed:27346674). For example, upon glutamate induction, promotes
CC       nuclear localization of HSP70/HSPA1A to inhibit ERK activation via
CC       VHR/DUSP3 phosphatase (PubMed:27941812). {ECO:0000250|UniProtKB:Q8K3G5,
CC       ECO:0000269|PubMed:14645249, ECO:0000269|PubMed:19141289,
CC       ECO:0000269|PubMed:25899223, ECO:0000269|PubMed:27346674,
CC       ECO:0000269|PubMed:27941812}.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=ATP + L-seryl-[protein] = ADP + H(+) + O-phospho-L-seryl-
CC         [protein]; Xref=Rhea:RHEA:17989, Rhea:RHEA-COMP:9863, Rhea:RHEA-
CC         COMP:11604, ChEBI:CHEBI:15378, ChEBI:CHEBI:29999, ChEBI:CHEBI:30616,
CC         ChEBI:CHEBI:83421, ChEBI:CHEBI:456216; EC=2.7.11.22;
CC         Evidence={ECO:0000269|PubMed:25899223};
CC   -!- SUBUNIT: Interacts with DUSP3 (PubMed:27346674, PubMed:27941812).
CC       Interacts with RAN. Interacts with HSP70/HSPA1A (PubMed:27941812).
CC       {ECO:0000250, ECO:0000269|PubMed:18617507,
CC       ECO:0000269|PubMed:27941812}.
CC   -!- INTERACTION:
CC       Q8IV63; P61244: MAX; NbExp=2; IntAct=EBI-1058605, EBI-751711;
CC   -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:14645249,
CC       ECO:0000269|PubMed:27346674, ECO:0000269|PubMed:33067254}. Cytoplasm
CC       {ECO:0000269|PubMed:33067254}. Note=Under oxidative stress, migrates
CC       from the nucleus to the cytoplasm. {ECO:0000269|PubMed:33067254}.
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Alternative splicing; Named isoforms=3;
CC       Name=1;
CC         IsoId=Q8IV63-1; Sequence=Displayed;
CC       Name=2;
CC         IsoId=Q8IV63-2; Sequence=VSP_008544, VSP_008545;
CC       Name=3;
CC         IsoId=Q8IV63-3; Sequence=VSP_043409;
CC   -!- PTM: Phosphorylated at Ser-108 by CDK5; leading to protection of the
CC       cell against H2O2-induced apoptosis. {ECO:0000269|PubMed:25899223}.
CC   -!- PTM: Ubiquitinated by RNF144A. {ECO:0000269|PubMed:33067254}.
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|PubMed:19141289}.
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DR   EMBL; AB031052; BAA90769.1; -; mRNA.
DR   EMBL; AF514788; AAP47180.1; -; mRNA.
DR   EMBL; AK292918; BAF85607.1; -; mRNA.
DR   EMBL; AK303010; BAG64141.1; -; mRNA.
DR   EMBL; AC011452; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; BC023556; AAH23556.1; -; mRNA.
DR   EMBL; BC095449; AAH95449.1; -; mRNA.
DR   CCDS; CCDS12791.1; -. [Q8IV63-1]
DR   CCDS; CCDS33076.1; -. [Q8IV63-3]
DR   CCDS; CCDS77334.1; -. [Q8IV63-2]
DR   RefSeq; NP_001020949.1; NM_001025778.1. [Q8IV63-3]
DR   RefSeq; NP_001295349.1; NM_001308420.1. [Q8IV63-2]
DR   RefSeq; NP_057524.3; NM_016440.3. [Q8IV63-1]
DR   RefSeq; XP_005259028.1; XM_005258971.3. [Q8IV63-1]
DR   RefSeq; XP_005259029.1; XM_005258972.3. [Q8IV63-3]
DR   RefSeq; XP_006723300.1; XM_006723237.3. [Q8IV63-1]
DR   RefSeq; XP_006723301.1; XM_006723238.3. [Q8IV63-3]
DR   RefSeq; XP_011525325.1; XM_011527023.2.
DR   PDB; 2JII; X-ray; 2.00 A; A/B=146-474.
DR   PDBsum; 2JII; -.
DR   AlphaFoldDB; Q8IV63; -.
DR   SMR; Q8IV63; -.
DR   BioGRID; 119394; 144.
DR   IntAct; Q8IV63; 27.
DR   MINT; Q8IV63; -.
DR   STRING; 9606.ENSP00000469880; -.
DR   ChEMBL; CHEMBL3430761; -.
DR   GlyGen; Q8IV63; 2 sites, 1 O-linked glycan (2 sites).
DR   iPTMnet; Q8IV63; -.
DR   PhosphoSitePlus; Q8IV63; -.
DR   BioMuta; VRK3; -.
DR   DMDM; 45593724; -.
DR   CPTAC; non-CPTAC-6010; -.
DR   CPTAC; non-CPTAC-6011; -.
DR   EPD; Q8IV63; -.
DR   jPOST; Q8IV63; -.
DR   MassIVE; Q8IV63; -.
DR   MaxQB; Q8IV63; -.
DR   PaxDb; 9606-ENSP00000469880; -.
DR   PeptideAtlas; Q8IV63; -.
DR   ProteomicsDB; 70666; -. [Q8IV63-1]
DR   ProteomicsDB; 70667; -. [Q8IV63-2]
DR   ProteomicsDB; 70668; -. [Q8IV63-3]
DR   Pumba; Q8IV63; -.
DR   TopDownProteomics; Q8IV63-1; -. [Q8IV63-1]
DR   Antibodypedia; 18806; 112 antibodies from 26 providers.
DR   DNASU; 51231; -.
DR   Ensembl; ENST00000316763.8; ENSP00000324636.2; ENSG00000105053.11. [Q8IV63-1]
DR   Ensembl; ENST00000377011.6; ENSP00000366210.1; ENSG00000105053.11. [Q8IV63-3]
DR   Ensembl; ENST00000594092.5; ENSP00000472541.1; ENSG00000105053.11. [Q8IV63-2]
DR   Ensembl; ENST00000594948.5; ENSP00000473171.1; ENSG00000105053.11. [Q8IV63-1]
DR   Ensembl; ENST00000599538.5; ENSP00000469880.1; ENSG00000105053.11. [Q8IV63-1]
DR   Ensembl; ENST00000601341.5; ENSP00000470156.1; ENSG00000105053.11. [Q8IV63-3]
DR   GeneID; 51231; -.
DR   KEGG; hsa:51231; -.
DR   MANE-Select; ENST00000316763.8; ENSP00000324636.2; NM_016440.4; NP_057524.3.
DR   UCSC; uc002prg.3; human. [Q8IV63-1]
DR   AGR; HGNC:18996; -.
DR   CTD; 51231; -.
DR   DisGeNET; 51231; -.
DR   GeneCards; VRK3; -.
DR   HGNC; HGNC:18996; VRK3.
DR   HPA; ENSG00000105053; Tissue enhanced (testis).
DR   MIM; 619771; gene.
DR   neXtProt; NX_Q8IV63; -.
DR   OpenTargets; ENSG00000105053; -.
DR   PharmGKB; PA134923990; -.
DR   VEuPathDB; HostDB:ENSG00000105053; -.
DR   eggNOG; KOG1164; Eukaryota.
DR   GeneTree; ENSGT00940000158111; -.
DR   InParanoid; Q8IV63; -.
DR   OMA; YCMVKWL; -.
DR   OrthoDB; 4064676at2759; -.
DR   PhylomeDB; Q8IV63; -.
DR   TreeFam; TF106473; -.
DR   PathwayCommons; Q8IV63; -.
DR   Reactome; R-HSA-202670; ERKs are inactivated.
DR   SignaLink; Q8IV63; -.
DR   SIGNOR; Q8IV63; -.
DR   BioGRID-ORCS; 51231; 9 hits in 1193 CRISPR screens.
DR   ChiTaRS; VRK3; human.
DR   EvolutionaryTrace; Q8IV63; -.
DR   GenomeRNAi; 51231; -.
DR   Pharos; Q8IV63; Tbio.
DR   PRO; PR:Q8IV63; -.
DR   Proteomes; UP000005640; Chromosome 19.
DR   RNAct; Q8IV63; Protein.
DR   Bgee; ENSG00000105053; Expressed in sperm and 192 other cell types or tissues.
DR   ExpressionAtlas; Q8IV63; baseline and differential.
DR   GO; GO:0043231; C:intracellular membrane-bounded organelle; IDA:HPA.
DR   GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR   GO; GO:0005634; C:nucleus; HDA:UniProtKB.
DR   GO; GO:0005524; F:ATP binding; IEA:InterPro.
DR   GO; GO:0019903; F:protein phosphatase binding; IDA:MGI.
DR   GO; GO:0004674; F:protein serine/threonine kinase activity; IBA:GO_Central.
DR   GO; GO:0070373; P:negative regulation of ERK1 and ERK2 cascade; IEA:Ensembl.
DR   GO; GO:0007165; P:signal transduction; IBA:GO_Central.
DR   GO; GO:0007519; P:skeletal muscle tissue development; IGI:FlyBase.
DR   Gene3D; 1.10.510.10; Transferase(Phosphotransferase) domain 1; 1.
DR   InterPro; IPR011009; Kinase-like_dom_sf.
DR   InterPro; IPR000719; Prot_kinase_dom.
DR   InterPro; IPR026870; Zinc_ribbon_dom.
DR   PANTHER; PTHR11909; CASEIN KINASE-RELATED; 1.
DR   PANTHER; PTHR11909:SF99; INACTIVE SERINE_THREONINE-PROTEIN KINASE VRK3; 1.
DR   Pfam; PF00069; Pkinase; 1.
DR   Pfam; PF13240; zinc_ribbon_2; 1.
DR   SMART; SM00220; S_TKc; 1.
DR   SUPFAM; SSF56112; Protein kinase-like (PK-like); 1.
DR   PROSITE; PS50011; PROTEIN_KINASE_DOM; 1.
DR   Genevisible; Q8IV63; HS.
PE   1: Evidence at protein level;
KW   3D-structure; Alternative splicing; Cytoplasm; Nucleotide-binding; Nucleus;
KW   Phosphoprotein; Reference proteome; Transferase; Ubl conjugation.
FT   CHAIN           1..474
FT                   /note="Serine/threonine-protein kinase VRK3"
FT                   /id="PRO_0000086808"
FT   DOMAIN          166..457
FT                   /note="Protein kinase"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT   REGION          41..152
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        41..85
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        92..152
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   MOD_RES         54
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:23186163"
FT   MOD_RES         55
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:18669648"
FT   MOD_RES         59
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:18669648,
FT                   ECO:0007744|PubMed:23186163"
FT   MOD_RES         82
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:19690332,
FT                   ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:21406692"
FT   MOD_RES         83
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:19690332,
FT                   ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:21406692,
FT                   ECO:0007744|PubMed:23186163"
FT   MOD_RES         90
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:19690332"
FT   MOD_RES         108
FT                   /note="Phosphoserine; by CDK5"
FT                   /evidence="ECO:0000269|PubMed:27346674"
FT   MOD_RES         115
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:21406692"
FT   MOD_RES         122
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:21406692"
FT   VAR_SEQ         47..96
FT                   /note="Missing (in isoform 3)"
FT                   /evidence="ECO:0000303|PubMed:14702039"
FT                   /id="VSP_043409"
FT   VAR_SEQ         407..412
FT                   /note="FVDKPG -> LPWDSF (in isoform 2)"
FT                   /evidence="ECO:0000303|PubMed:15489334"
FT                   /id="VSP_008544"
FT   VAR_SEQ         413..474
FT                   /note="Missing (in isoform 2)"
FT                   /evidence="ECO:0000303|PubMed:15489334"
FT                   /id="VSP_008545"
FT   VARIANT         59
FT                   /note="S -> F (in dbSNP:rs2033262)"
FT                   /evidence="ECO:0000269|PubMed:17344846"
FT                   /id="VAR_041295"
FT   VARIANT         105
FT                   /note="P -> T (in dbSNP:rs11547882)"
FT                   /evidence="ECO:0000269|PubMed:17344846"
FT                   /id="VAR_041296"
FT   VARIANT         170
FT                   /note="S -> P (in dbSNP:rs11547881)"
FT                   /id="VAR_051682"
FT   VARIANT         171
FT                   /note="F -> L (in dbSNP:rs11547883)"
FT                   /evidence="ECO:0000269|PubMed:17344846"
FT                   /id="VAR_041297"
FT   VARIANT         188
FT                   /note="T -> A (in dbSNP:rs11879620)"
FT                   /id="VAR_051683"
FT   VARIANT         268
FT                   /note="S -> L (in dbSNP:rs10410075)"
FT                   /evidence="ECO:0000269|PubMed:17344846"
FT                   /id="VAR_041298"
FT   VARIANT         288
FT                   /note="C -> Y (in dbSNP:rs10409482)"
FT                   /evidence="ECO:0000269|PubMed:17344846"
FT                   /id="VAR_041299"
FT   VARIANT         304
FT                   /note="H -> L (in dbSNP:rs35261919)"
FT                   /id="VAR_051684"
FT   VARIANT         370
FT                   /note="R -> C (in dbSNP:rs35331034)"
FT                   /evidence="ECO:0000269|PubMed:17344846"
FT                   /id="VAR_041300"
FT   VARIANT         371
FT                   /note="S -> G (in dbSNP:rs56407496)"
FT                   /evidence="ECO:0000269|PubMed:17344846"
FT                   /id="VAR_041301"
FT   MUTAGEN         108
FT                   /note="S->A: Unable to be phosphorylated by CDK5."
FT                   /evidence="ECO:0000269|PubMed:27346674"
FT   MUTAGEN         203
FT                   /note="K->E: Complete loss of kinase activity."
FT                   /evidence="ECO:0000269|PubMed:25899223"
FT   CONFLICT        161
FT                   /note="K -> E (in Ref. 2; AAP47180)"
FT                   /evidence="ECO:0000305"
FT   HELIX           142..148
FT                   /evidence="ECO:0007829|PDB:2JII"
FT   STRAND          157..159
FT                   /evidence="ECO:0007829|PDB:2JII"
FT   STRAND          165..175
FT                   /evidence="ECO:0007829|PDB:2JII"
FT   STRAND          178..185
FT                   /evidence="ECO:0007829|PDB:2JII"
FT   STRAND          200..206
FT                   /evidence="ECO:0007829|PDB:2JII"
FT   HELIX           211..221
FT                   /evidence="ECO:0007829|PDB:2JII"
FT   HELIX           224..233
FT                   /evidence="ECO:0007829|PDB:2JII"
FT   STRAND          246..250
FT                   /evidence="ECO:0007829|PDB:2JII"
FT   TURN            251..253
FT                   /evidence="ECO:0007829|PDB:2JII"
FT   STRAND          254..260
FT                   /evidence="ECO:0007829|PDB:2JII"
FT   HELIX           266..272
FT                   /evidence="ECO:0007829|PDB:2JII"
FT   HELIX           274..276
FT                   /evidence="ECO:0007829|PDB:2JII"
FT   HELIX           280..299
FT                   /evidence="ECO:0007829|PDB:2JII"
FT   STRAND          311..315
FT                   /evidence="ECO:0007829|PDB:2JII"
FT   STRAND          318..324
FT                   /evidence="ECO:0007829|PDB:2JII"
FT   HELIX           327..329
FT                   /evidence="ECO:0007829|PDB:2JII"
FT   HELIX           335..337
FT                   /evidence="ECO:0007829|PDB:2JII"
FT   TURN            354..356
FT                   /evidence="ECO:0007829|PDB:2JII"
FT   HELIX           359..362
FT                   /evidence="ECO:0007829|PDB:2JII"
FT   HELIX           369..385
FT                   /evidence="ECO:0007829|PDB:2JII"
FT   HELIX           391..393
FT                   /evidence="ECO:0007829|PDB:2JII"
FT   HELIX           397..409
FT                   /evidence="ECO:0007829|PDB:2JII"
FT   HELIX           426..436
FT                   /evidence="ECO:0007829|PDB:2JII"
FT   HELIX           446..459
FT                   /evidence="ECO:0007829|PDB:2JII"
SQ   SEQUENCE   474 AA;  52881 MW;  86B9B91050A7F0CC CRC64;
     MISFCPDCGK SIQAAFKFCP YCGNSLPVEE HVGSQTFVNP HVSSFQGSKR GLNSSFETSP
     KKVKWSSTVT SPRLSLFSDG DSSESEDTLS SSERSKGSGS RPPTPKSSPQ KTRKSPQVTR
     GSPQKTSCSP QKTRQSPQTL KRSRVTTSLE ALPTGTVLTD KSGRQWKLKS FQTRDNQGIL
     YEAAPTSTLT CDSGPQKQKF SLKLDAKDGR LFNEQNFFQR AAKPLQVNKW KKLYSTPLLA
     IPTCMGFGVH QDKYRFLVLP SLGRSLQSAL DVSPKHVLSE RSVLQVACRL LDALEFLHEN
     EYVHGNVTAE NIFVDPEDQS QVTLAGYGFA FRYCPSGKHV AYVEGSRSPH EGDLEFISMD
     LHKGCGPSRR SDLQSLGYCM LKWLYGFLPW TNCLPNTEDI MKQKQKFVDK PGPFVGPCGH
     WIRPSETLQK YLKVVMALTY EEKPPYAMLR NNLEALLQDL RVSPYDPIGL PMVP
//