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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
 
 
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