VRK1_HUMAN
ID VRK1_HUMAN Reviewed; 396 AA.
AC Q99986; Q3SYL2;
DT 10-OCT-2003, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-1997, sequence version 1.
DT 03-AUG-2022, entry version 202.
DE RecName: Full=Serine/threonine-protein kinase VRK1 {ECO:0000305};
DE EC=2.7.11.1 {ECO:0000269|PubMed:21543316};
DE AltName: Full=Vaccinia-related kinase 1 {ECO:0000303|PubMed:9344656};
GN Name=VRK1 {ECO:0000303|PubMed:9344656, ECO:0000312|HGNC:HGNC:12718};
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], AND TISSUE SPECIFICITY.
RC TISSUE=Fetal liver;
RX PubMed=9344656; DOI=10.1006/geno.1997.4938;
RA Nezu J., Oku A., Jones M.H., Shimane M.;
RT "Identification of two novel human putative serine/threonine kinases, VRK1
RT and VRK2, with structural similarity to Vaccinia virus B1R kinase.";
RL Genomics 45:327-331(1997).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain, and Lung;
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 FUNCTION, SUBCELLULAR LOCATION, AUTOPHOSPHORYLATION, AND MUTAGENESIS OF
RP SER-14; THR-102; SER-125; SER-150; SER-158; SER-239; THR-305; THR-312;
RP THR-355 AND THR-390.
RX PubMed=10951572; DOI=10.1038/sj.onc.1203709;
RA Lopez-Borges S., Lazo P.A.;
RT "The human vaccinia-related kinase 1 (VRK1) phosphorylates threonine-18
RT within the mdm-2 binding site of the p53 tumour suppressor protein.";
RL Oncogene 19:3656-3664(2000).
RN [4]
RP PHOSPHORYLATION AT THR-355, AND ACTIVITY REGULATION.
RX PubMed=11883897; DOI=10.1006/abbi.2001.2746;
RA Barcia R., Lopez-Borges S., Vega F.M., Lazo P.A.;
RT "Kinetic properties of p53 phosphorylation by the human vaccinia-related
RT kinase 1.";
RL Arch. Biochem. Biophys. 399:1-5(2002).
RN [5]
RP FUNCTION, SUBCELLULAR LOCATION, AND PHOSPHORYLATION.
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 [6]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=15105425; DOI=10.1074/jbc.m401009200;
RA Sevilla A., Santos C.R., Vega F.M., Lazo P.A.;
RT "Human vaccinia-related kinase 1 (VRK1) activates the ATF2 transcriptional
RT activity by novel phosphorylation on Thr-73 and Ser-62 and cooperates with
RT JNK.";
RL J. Biol. Chem. 279:27458-27465(2004).
RN [7]
RP SUBCELLULAR LOCATION.
RX PubMed=16704422; DOI=10.1111/j.1742-4658.2006.05256.x;
RA Blanco S., Klimcakova L., Vega F.M., Lazo P.A.;
RT "The subcellular localization of vaccinia-related kinase-2 (VRK2) isoforms
RT determines their different effect on p53 stability in tumour cell lines.";
RL FEBS J. 273:2487-2504(2006).
RN [8]
RP FUNCTION.
RX PubMed=16495336; DOI=10.1091/mbc.e05-12-1179;
RA Nichols R.J., Wiebe M.S., Traktman P.;
RT "The vaccinia-related kinases phosphorylate the N' terminus of BAF,
RT regulating its interaction with DNA and its retention in the nucleus.";
RL Mol. Biol. Cell 17:2451-2464(2006).
RN [9]
RP FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH RAN, AND ACTIVITY
RP REGULATION.
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 [10]
RP INVOLVEMENT IN PCH1A.
RX PubMed=19646678; DOI=10.1016/j.ajhg.2009.07.006;
RA Renbaum P., Kellerman E., Jaron R., Geiger D., Segel R., Lee M., King M.C.,
RA Levy-Lahad E.;
RT "Spinal muscular atrophy with pontocerebellar hypoplasia is caused by a
RT mutation in the VRK1 gene.";
RL Am. J. Hum. Genet. 85:281-289(2009).
RN [11]
RP FUNCTION, PHOSPHORYLATION AT SER-342, AND MUTAGENESIS OF LYS-179 AND
RP SER-342.
RX PubMed=19103756; DOI=10.1128/mcb.01341-08;
RA Lopez-Sanchez I., Sanz-Garcia M., Lazo P.A.;
RT "Plk3 interacts with and specifically phosphorylates VRK1 in Ser342, a
RT downstream target in a pathway that induces Golgi fragmentation.";
RL Mol. Cell. Biol. 29:1189-1201(2009).
RN [12]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-342, 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 [13]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [14]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-342; SER-376 AND THR-378, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=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 [15]
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 [16]
RP SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-71, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=28112733; DOI=10.1038/nsmb.3366;
RA Hendriks I.A., Lyon D., Young C., Jensen L.J., Vertegaal A.C.,
RA Nielsen M.L.;
RT "Site-specific mapping of the human SUMO proteome reveals co-modification
RT with phosphorylation.";
RL Nat. Struct. Mol. Biol. 24:325-336(2017).
RN [17]
RP FUNCTION.
RX PubMed=33076429; DOI=10.3390/cancers12102986;
RA Garcia-Gonzalez R., Morejon-Garcia P., Campillo-Marcos I., Salzano M.,
RA Lazo P.A.;
RT "VRK1 phosphorylates Tip60/KAT5 and is required for H4K16 acetylation in
RT response to DNA Damage.";
RL Cancers 12:0-0(2020).
RN [18]
RP INTERACTION WITH VACCINIA VIRUS PROTEIN B12 (MICROBIAL INFECTION).
RX PubMed=33177193; DOI=10.1128/jvi.02114-20;
RA Rico A.B., Linville A.C., Olson A.T., Wang Z., Wiebe M.S.;
RT "The Vaccinia Virus B12 Pseudokinase Represses Viral Replication via
RT Interaction with the Cellular Kinase VRK1 and Activation of the Antiviral
RT Effector BAF.";
RL J. Virol. 95:0-0(2021).
RN [19]
RP X-RAY CRYSTALLOGRAPHY (2.4 ANGSTROMS) OF 3-364 IN COMPLEX WITH INHIBITOR.
RG Structural genomics consortium (SGC);
RT "Human vaccinia-related kinase 1.";
RL Submitted (SEP-2010) to the PDB data bank.
RN [20]
RP STRUCTURE BY NMR, CATALYTIC ACTIVITY, MUTAGENESIS OF SER-342 AND THR-353,
RP AND AUTOPHOSPHORYLATION.
RX PubMed=21543316; DOI=10.1074/jbc.m110.200162;
RA Shin J., Chakraborty G., Bharatham N., Kang C., Tochio N., Koshiba S.,
RA Kigawa T., Kim W., Kim K.T., Yoon H.S.;
RT "NMR solution structure of human vaccinia-related kinase 1 (VRK1) reveals
RT the C-terminal tail essential for its structural stability and
RT autocatalytic activity.";
RL J. Biol. Chem. 286:22131-22138(2011).
CC -!- FUNCTION: Serine/threonine kinase involved in cell cycle, nuclear
CC condensation and transcription regulation (PubMed:14645249,
CC PubMed:18617507, PubMed:19103756). Involved in Golgi disassembly during
CC the cell cycle: following phosphorylation by PLK3 during mitosis,
CC required to induce Golgi fragmentation (PubMed:19103756).
CC Phosphorylates 'Thr-18' of p53/TP53 and may thereby prevent the
CC interaction between p53/TP53 and MDM2 (PubMed:10951572). Phosphorylates
CC KAT5 in response to DNA damage, promoting KAT5 association with
CC chromatin and histone acetyltransferase activity (PubMed:33076429).
CC Phosphorylates BANF1: disrupts its ability to bind DNA, reduces its
CC binding to LEM domain-containing proteins and causes its relocalization
CC from the nucleus to the cytoplasm (PubMed:16495336). Phosphorylates
CC ATF2 which activates its transcriptional activity (PubMed:15105425).
CC {ECO:0000269|PubMed:10951572, ECO:0000269|PubMed:14645249,
CC ECO:0000269|PubMed:15105425, ECO:0000269|PubMed:16495336,
CC ECO:0000269|PubMed:18617507, ECO:0000269|PubMed:19103756,
CC ECO:0000269|PubMed:33076429}.
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=2.7.11.1;
CC Evidence={ECO:0000269|PubMed:21543316};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-threonyl-[protein] = ADP + H(+) + O-phospho-L-
CC threonyl-[protein]; Xref=Rhea:RHEA:46608, Rhea:RHEA-COMP:11060,
CC Rhea:RHEA-COMP:11605, ChEBI:CHEBI:15378, ChEBI:CHEBI:30013,
CC ChEBI:CHEBI:30616, ChEBI:CHEBI:61977, ChEBI:CHEBI:456216;
CC EC=2.7.11.1; Evidence={ECO:0000269|PubMed:21543316};
CC -!- ACTIVITY REGULATION: Active in presence of Mn(2+), Mg(2+) and Zn(2+),
CC but is not functional with Ca(2+) or Cu(2+) (PubMed:11883897). Has a
CC higher affinity for Mn(2+) than for Mg(2+) (PubMed:11883897). RAN
CC inhibits its autophosphorylation and its ability to phosphorylate
CC histone H3 (PubMed:18617507). {ECO:0000269|PubMed:11883897,
CC ECO:0000269|PubMed:18617507}.
CC -!- SUBUNIT: (Microbial infection) Interacts with vaccinia protein B12;
CC this interaction inhibits the repressive activity of the vaccinia virus
CC B12 pseudokinase on viral replication factory formation.
CC {ECO:0000269|PubMed:33177193}.
CC -!- INTERACTION:
CC Q99986; P15336: ATF2; NbExp=5; IntAct=EBI-1769146, EBI-1170906;
CC Q99986; Q96GD4: AURKB; NbExp=14; IntAct=EBI-1769146, EBI-624291;
CC Q99986; P38432: COIL; NbExp=9; IntAct=EBI-1769146, EBI-945751;
CC Q99986; P16104: H2AX; NbExp=3; IntAct=EBI-1769146, EBI-494830;
CC Q99986; P05412: JUN; NbExp=5; IntAct=EBI-1769146, EBI-852823;
CC Q99986; Q92993: KAT5; NbExp=6; IntAct=EBI-1769146, EBI-399080;
CC Q99986; O60934: NBN; NbExp=13; IntAct=EBI-1769146, EBI-494844;
CC Q99986; Q9H4B4: PLK3; NbExp=12; IntAct=EBI-1769146, EBI-751877;
CC Q99986; P62826: RAN; NbExp=12; IntAct=EBI-1769146, EBI-286642;
CC Q99986; O76064: RNF8; NbExp=2; IntAct=EBI-1769146, EBI-373337;
CC Q99986; P48431: SOX2; NbExp=14; IntAct=EBI-1769146, EBI-6124081;
CC Q99986; P04637: TP53; NbExp=11; IntAct=EBI-1769146, EBI-366083;
CC Q99986; Q12888: TP53BP1; NbExp=8; IntAct=EBI-1769146, EBI-396540;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:10951572,
CC ECO:0000269|PubMed:14645249, ECO:0000269|PubMed:15105425,
CC ECO:0000269|PubMed:16704422, ECO:0000269|PubMed:18617507}. Cytoplasm
CC {ECO:0000269|PubMed:18617507}. Note=Dispersed throughout the cell but
CC not located on mitotic spindle or chromatids during mitosis.
CC -!- TISSUE SPECIFICITY: Widely expressed. Highly expressed in fetal liver,
CC testis and thymus. {ECO:0000269|PubMed:9344656}.
CC -!- PTM: Autophosphorylated at various serine and threonine residues
CC (PubMed:11883897, PubMed:14645249, PubMed:19103756, PubMed:21543316).
CC Autophosphorylation does not impair its ability to phosphorylate
CC p53/TP53 (PubMed:11883897). Phosphorylation by PLK3 leads to induction
CC of Golgi fragmentation during mitosis (PubMed:19103756).
CC {ECO:0000269|PubMed:11883897, ECO:0000269|PubMed:14645249,
CC ECO:0000269|PubMed:19103756, ECO:0000269|PubMed:21543316}.
CC -!- DISEASE: Pontocerebellar hypoplasia 1A (PCH1A) [MIM:607596]: A disorder
CC characterized by an abnormally small cerebellum and brainstem, central
CC and peripheral motor dysfunction from birth, gliosis and spinal cord
CC anterior horn cells degeneration resembling infantile spinal muscular
CC atrophy. Additional features include muscle hypotonia, congenital
CC contractures and respiratory insufficiency that is evident at birth.
CC {ECO:0000269|PubMed:19646678}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. CK1 Ser/Thr
CC protein kinase family. VRK subfamily. {ECO:0000305}.
CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and
CC Haematology;
CC URL="http://atlasgeneticsoncology.org/Genes/VRK1ID43556ch14q32.html";
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DR EMBL; AB000449; BAA19108.1; -; mRNA.
DR EMBL; BC103761; AAI03762.1; -; mRNA.
DR EMBL; BC112075; AAI12076.1; -; mRNA.
DR EMBL; BC113510; AAI13511.1; -; mRNA.
DR CCDS; CCDS9947.1; -.
DR RefSeq; NP_003375.1; NM_003384.2.
DR PDB; 2KTY; NMR; -; A=1-360.
DR PDB; 2KUL; NMR; -; A=1-360.
DR PDB; 2LAV; NMR; -; A=1-361.
DR PDB; 2RSV; NMR; -; A=1-396.
DR PDB; 3OP5; X-ray; 2.40 A; A/B/C/D=3-364.
DR PDB; 5UKF; X-ray; 2.40 A; A/B/C/D=3-364.
DR PDB; 5UVF; X-ray; 2.00 A; A/B/C/D=3-364.
DR PDB; 6AC9; X-ray; 2.07 A; A/B/C/D=1-364.
DR PDB; 6BP0; X-ray; 1.90 A; A/B/C/D=3-364.
DR PDB; 6BRU; X-ray; 1.80 A; A/B/C/D=3-364.
DR PDB; 6BTW; X-ray; 1.90 A; A/B/C/D=3-364.
DR PDB; 6BU6; X-ray; 1.80 A; A/B/C/D=3-364.
DR PDB; 6CFM; X-ray; 2.45 A; A/B/C/D=3-364.
DR PDB; 6CMM; X-ray; 2.10 A; A/B/C/D=3-364.
DR PDB; 6CNX; X-ray; 2.00 A; A/B/C/D=3-364.
DR PDB; 6CQH; X-ray; 2.15 A; A/B/C/D=3-364.
DR PDB; 6CSW; X-ray; 2.25 A; A/B/C/D=3-364.
DR PDB; 6DD4; X-ray; 2.10 A; A/B/C/D=3-364.
DR PDB; 6NPN; X-ray; 2.20 A; A/B/C/D=3-364.
DR PDB; 6VXU; X-ray; 2.00 A; A/B/C/D=3-364.
DR PDB; 6VZH; X-ray; 2.55 A; A/B/C/D=3-364.
DR PDB; 7M10; X-ray; 1.15 A; B=2-13.
DR PDBsum; 2KTY; -.
DR PDBsum; 2KUL; -.
DR PDBsum; 2LAV; -.
DR PDBsum; 2RSV; -.
DR PDBsum; 3OP5; -.
DR PDBsum; 5UKF; -.
DR PDBsum; 5UVF; -.
DR PDBsum; 6AC9; -.
DR PDBsum; 6BP0; -.
DR PDBsum; 6BRU; -.
DR PDBsum; 6BTW; -.
DR PDBsum; 6BU6; -.
DR PDBsum; 6CFM; -.
DR PDBsum; 6CMM; -.
DR PDBsum; 6CNX; -.
DR PDBsum; 6CQH; -.
DR PDBsum; 6CSW; -.
DR PDBsum; 6DD4; -.
DR PDBsum; 6NPN; -.
DR PDBsum; 6VXU; -.
DR PDBsum; 6VZH; -.
DR PDBsum; 7M10; -.
DR AlphaFoldDB; Q99986; -.
DR BMRB; Q99986; -.
DR SMR; Q99986; -.
DR BioGRID; 113282; 257.
DR CORUM; Q99986; -.
DR IntAct; Q99986; 42.
DR MINT; Q99986; -.
DR STRING; 9606.ENSP00000216639; -.
DR BindingDB; Q99986; -.
DR ChEMBL; CHEMBL1293199; -.
DR GlyGen; Q99986; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; Q99986; -.
DR PhosphoSitePlus; Q99986; -.
DR SwissPalm; Q99986; -.
DR BioMuta; VRK1; -.
DR DMDM; 45593726; -.
DR EPD; Q99986; -.
DR jPOST; Q99986; -.
DR MassIVE; Q99986; -.
DR MaxQB; Q99986; -.
DR PaxDb; Q99986; -.
DR PeptideAtlas; Q99986; -.
DR PRIDE; Q99986; -.
DR ProteomicsDB; 78563; -.
DR Antibodypedia; 42; 273 antibodies from 36 providers.
DR DNASU; 7443; -.
DR Ensembl; ENST00000216639.8; ENSP00000216639.3; ENSG00000100749.9.
DR Ensembl; ENST00000679816.1; ENSP00000506525.1; ENSG00000100749.9.
DR Ensembl; ENST00000680756.1; ENSP00000506648.1; ENSG00000100749.9.
DR Ensembl; ENST00000681344.1; ENSP00000506151.1; ENSG00000100749.9.
DR Ensembl; ENST00000681355.1; ENSP00000506214.1; ENSG00000100749.9.
DR GeneID; 7443; -.
DR KEGG; hsa:7443; -.
DR MANE-Select; ENST00000216639.8; ENSP00000216639.3; NM_003384.3; NP_003375.1.
DR UCSC; uc001yft.4; human.
DR CTD; 7443; -.
DR DisGeNET; 7443; -.
DR GeneCards; VRK1; -.
DR HGNC; HGNC:12718; VRK1.
DR HPA; ENSG00000100749; Tissue enhanced (bone marrow, testis).
DR MalaCards; VRK1; -.
DR MIM; 602168; gene.
DR MIM; 607596; phenotype.
DR neXtProt; NX_Q99986; -.
DR OpenTargets; ENSG00000100749; -.
DR Orphanet; 423894; Microcephaly-complex motor and sensory axonal neuropathy syndrome.
DR Orphanet; 2254; Pontocerebellar hypoplasia type 1.
DR PharmGKB; PA37330; -.
DR VEuPathDB; HostDB:ENSG00000100749; -.
DR eggNOG; KOG1164; Eukaryota.
DR GeneTree; ENSGT00940000155554; -.
DR HOGENOM; CLU_019279_4_0_1; -.
DR InParanoid; Q99986; -.
DR OMA; PDYDKCR; -.
DR OrthoDB; 866200at2759; -.
DR PhylomeDB; Q99986; -.
DR TreeFam; TF106473; -.
DR PathwayCommons; Q99986; -.
DR Reactome; R-HSA-2980766; Nuclear Envelope Breakdown.
DR Reactome; R-HSA-2995383; Initiation of Nuclear Envelope (NE) Reformation.
DR SignaLink; Q99986; -.
DR SIGNOR; Q99986; -.
DR BioGRID-ORCS; 7443; 442 hits in 1119 CRISPR screens.
DR ChiTaRS; VRK1; human.
DR EvolutionaryTrace; Q99986; -.
DR GeneWiki; VRK1; -.
DR GenomeRNAi; 7443; -.
DR Pharos; Q99986; Tbio.
DR PRO; PR:Q99986; -.
DR Proteomes; UP000005640; Chromosome 14.
DR RNAct; Q99986; protein.
DR Bgee; ENSG00000100749; Expressed in oocyte and 195 other tissues.
DR ExpressionAtlas; Q99986; baseline and differential.
DR Genevisible; Q99986; HS.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005829; C:cytosol; IDA:HPA.
DR GO; GO:0005795; C:Golgi stack; IDA:UniProtKB.
DR GO; GO:0005730; C:nucleolus; IDA:HPA.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0042393; F:histone binding; IPI:GO_Central.
DR GO; GO:0035175; F:histone kinase activity (H3-S10 specific); IDA:UniProtKB.
DR GO; GO:0072354; F:histone kinase activity (H3-T3 specific); IDA:UniProtKB.
DR GO; GO:0004672; F:protein kinase activity; IDA:UniProtKB.
DR GO; GO:0019901; F:protein kinase binding; IDA:MGI.
DR GO; GO:0106310; F:protein serine kinase activity; IEA:RHEA.
DR GO; GO:0004674; F:protein serine/threonine kinase activity; IDA:UniProtKB.
DR GO; GO:0051301; P:cell division; IEA:UniProtKB-KW.
DR GO; GO:0006974; P:cellular response to DNA damage stimulus; IDA:UniProtKB.
DR GO; GO:0090166; P:Golgi disassembly; IDA:UniProtKB.
DR GO; GO:0016572; P:histone phosphorylation; IBA:GO_Central.
DR GO; GO:0007077; P:mitotic nuclear membrane disassembly; TAS:Reactome.
DR GO; GO:0018105; P:peptidyl-serine phosphorylation; IBA:GO_Central.
DR GO; GO:0120187; P:positive regulation of protein localization to chromatin; IDA:UniProtKB.
DR GO; GO:0046777; P:protein autophosphorylation; IDA:UniProtKB.
DR GO; GO:0006468; P:protein phosphorylation; TAS:ProtInc.
DR GO; GO:0007165; P:signal transduction; IBA:GO_Central.
DR InterPro; IPR011009; Kinase-like_dom_sf.
DR InterPro; IPR000719; Prot_kinase_dom.
DR InterPro; IPR017441; Protein_kinase_ATP_BS.
DR InterPro; IPR008271; Ser/Thr_kinase_AS.
DR Pfam; PF00069; Pkinase; 1.
DR SMART; SM00220; S_TKc; 1.
DR SUPFAM; SSF56112; SSF56112; 1.
DR PROSITE; PS00107; PROTEIN_KINASE_ATP; 1.
DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 1.
DR PROSITE; PS00108; PROTEIN_KINASE_ST; 1.
PE 1: Evidence at protein level;
KW 3D-structure; ATP-binding; Cell cycle; Cell division; Cytoplasm;
KW Host-virus interaction; Isopeptide bond; Kinase; Mitosis;
KW Neurodegeneration; Nucleotide-binding; Nucleus; Phosphoprotein;
KW Reference proteome; Serine/threonine-protein kinase; Transferase;
KW Ubl conjugation.
FT CHAIN 1..396
FT /note="Serine/threonine-protein kinase VRK1"
FT /id="PRO_0000086803"
FT DOMAIN 37..317
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT REGION 354..396
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 356..371
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 177
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT ECO:0000255|PROSITE-ProRule:PRU10027"
FT BINDING 43..51
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 71
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT MOD_RES 342
FT /note="Phosphoserine; by PLK3"
FT /evidence="ECO:0000269|PubMed:19103756,
FT ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:23186163"
FT MOD_RES 355
FT /note="Phosphothreonine; by autocatalysis"
FT /evidence="ECO:0000269|PubMed:11883897"
FT MOD_RES 376
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 378
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT CROSSLNK 71
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:28112733"
FT MUTAGEN 14
FT /note="S->A: Does not abolish autophosphorylation."
FT /evidence="ECO:0000269|PubMed:10951572"
FT MUTAGEN 102
FT /note="T->A: Does not abolish autophosphorylation."
FT /evidence="ECO:0000269|PubMed:10951572"
FT MUTAGEN 125
FT /note="S->A: Does not abolish autophosphorylation."
FT /evidence="ECO:0000269|PubMed:10951572"
FT MUTAGEN 150
FT /note="S->A: Does not abolish autophosphorylation."
FT /evidence="ECO:0000269|PubMed:10951572"
FT MUTAGEN 158
FT /note="S->A: Does not abolish autophosphorylation."
FT /evidence="ECO:0000269|PubMed:10951572"
FT MUTAGEN 179
FT /note="K->A: Does not affect phosphorylation at S-342."
FT /evidence="ECO:0000269|PubMed:19103756"
FT MUTAGEN 239
FT /note="S->A: Does not abolish autophosphorylation."
FT /evidence="ECO:0000269|PubMed:10951572"
FT MUTAGEN 305
FT /note="T->A: Does not abolish autophosphorylation."
FT /evidence="ECO:0000269|PubMed:10951572"
FT MUTAGEN 312
FT /note="T->A: Does not abolish autophosphorylation."
FT /evidence="ECO:0000269|PubMed:10951572"
FT MUTAGEN 342
FT /note="S->A: Abolishes phosphorylation by PLK3 and
FT induction of Golgi fragmentation during mitosis. Strongly
FT reduced autophosphorylation."
FT /evidence="ECO:0000269|PubMed:19103756,
FT ECO:0000269|PubMed:21543316"
FT MUTAGEN 353
FT /note="T->A: Strongly reduced autophosphorylation."
FT /evidence="ECO:0000269|PubMed:21543316"
FT MUTAGEN 355
FT /note="T->A: Does not abolish autophosphorylation."
FT /evidence="ECO:0000269|PubMed:10951572"
FT MUTAGEN 390
FT /note="T->A: Does not abolish autophosphorylation."
FT /evidence="ECO:0000269|PubMed:10951572"
FT TURN 2..4
FT /evidence="ECO:0007829|PDB:2LAV"
FT STRAND 11..13
FT /evidence="ECO:0007829|PDB:2LAV"
FT STRAND 22..24
FT /evidence="ECO:0007829|PDB:2KUL"
FT STRAND 28..30
FT /evidence="ECO:0007829|PDB:6BRU"
FT STRAND 36..42
FT /evidence="ECO:0007829|PDB:6BRU"
FT STRAND 45..47
FT /evidence="ECO:0007829|PDB:6BRU"
FT STRAND 51..56
FT /evidence="ECO:0007829|PDB:6BRU"
FT STRAND 58..60
FT /evidence="ECO:0007829|PDB:6BTW"
FT STRAND 67..74
FT /evidence="ECO:0007829|PDB:6BRU"
FT HELIX 78..90
FT /evidence="ECO:0007829|PDB:6BRU"
FT HELIX 93..102
FT /evidence="ECO:0007829|PDB:6BRU"
FT STRAND 113..121
FT /evidence="ECO:0007829|PDB:6BRU"
FT STRAND 124..132
FT /evidence="ECO:0007829|PDB:6BRU"
FT STRAND 134..137
FT /evidence="ECO:0007829|PDB:6BRU"
FT HELIX 138..144
FT /evidence="ECO:0007829|PDB:6BRU"
FT TURN 145..147
FT /evidence="ECO:0007829|PDB:6VXU"
FT HELIX 151..170
FT /evidence="ECO:0007829|PDB:6BRU"
FT HELIX 180..182
FT /evidence="ECO:0007829|PDB:6BRU"
FT STRAND 183..188
FT /evidence="ECO:0007829|PDB:6BRU"
FT STRAND 193..195
FT /evidence="ECO:0007829|PDB:6BRU"
FT HELIX 198..200
FT /evidence="ECO:0007829|PDB:6VZH"
FT STRAND 202..205
FT /evidence="ECO:0007829|PDB:6BRU"
FT HELIX 206..208
FT /evidence="ECO:0007829|PDB:6BRU"
FT TURN 225..227
FT /evidence="ECO:0007829|PDB:6BRU"
FT HELIX 230..233
FT /evidence="ECO:0007829|PDB:6BRU"
FT HELIX 240..256
FT /evidence="ECO:0007829|PDB:6BRU"
FT TURN 260..263
FT /evidence="ECO:0007829|PDB:6BRU"
FT HELIX 268..280
FT /evidence="ECO:0007829|PDB:6BRU"
FT HELIX 282..289
FT /evidence="ECO:0007829|PDB:6BRU"
FT HELIX 291..293
FT /evidence="ECO:0007829|PDB:5UKF"
FT HELIX 297..307
FT /evidence="ECO:0007829|PDB:6BRU"
FT STRAND 311..313
FT /evidence="ECO:0007829|PDB:2KTY"
FT HELIX 317..330
FT /evidence="ECO:0007829|PDB:6BRU"
FT STRAND 355..357
FT /evidence="ECO:0007829|PDB:2KTY"
SQ SEQUENCE 396 AA; 45476 MW; 5640C624BF059949 CRC64;
MPRVKAAQAG RQSSAKRHLA EQFAVGEIIT DMAKKEWKVG LPIGQGGFGC IYLADMNSSE
SVGSDAPCVV KVEPSDNGPL FTELKFYQRA AKPEQIQKWI RTRKLKYLGV PKYWGSGLHD
KNGKSYRFMI MDRFGSDLQK IYEANAKRFS RKTVLQLSLR ILDILEYIHE HEYVHGDIKA
SNLLLNYKNP DQVYLVDYGL AYRYCPEGVH KEYKEDPKRC HDGTIEFTSI DAHNGVAPSR
RGDLEILGYC MIQWLTGHLP WEDNLKDPKY VRDSKIRYRE NIASLMDKCF PEKNKPGEIA
KYMETVKLLD YTEKPLYENL RDILLQGLKA IGSKDDGKLD LSVVENGGLK AKTITKKRKK
EIEESKEPGV EDTEWSNTQT EEAIQTRSRT RKRVQK
