VRK1_MOUSE
ID VRK1_MOUSE Reviewed; 440 AA.
AC Q80X41; O88635; O88636; Q8C2P7; Q91YH9;
DT 10-OCT-2003, integrated into UniProtKB/Swiss-Prot.
DT 10-OCT-2003, sequence version 2.
DT 03-AUG-2022, entry version 163.
DE RecName: Full=Serine/threonine-protein kinase VRK1 {ECO:0000305};
DE EC=2.7.11.1 {ECO:0000269|PubMed:14645249};
DE AltName: Full=Serine/threonine-protein kinase 51PK {ECO:0000303|PubMed:9521809};
DE AltName: Full=Vaccinia-related kinase 1 {ECO:0000303|PubMed:12782311};
GN Name=Vrk1 {ECO:0000303|PubMed:12782311, ECO:0000312|MGI:MGI:1261847};
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 [MRNA] (ISOFORMS 1 AND 3), PROTEIN SEQUENCE OF 19-33;
RP 267-275 AND 278-288, FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY,
RP AND AUTOPHOSPHORYLATION.
RC TISSUE=Testis;
RX PubMed=9521809; DOI=10.1006/abbi.1998.0582;
RA Zelko I.N., Kobayashi R., Honkakoski P., Negishi M.;
RT "Molecular cloning and characterization of a novel nuclear protein kinase
RT in mice.";
RL Arch. Biochem. Biophys. 352:31-36(1998).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1; 3 AND 5).
RC STRAIN=NOD; TISSUE=Olfactory bulb, 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 [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Mammary tumor, and Olfactory epithelium;
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 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 [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 IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Pancreas, and Spleen;
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 FUNCTION, AND MUTAGENESIS OF LYS-179.
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).
CC -!- FUNCTION: Serine/threonine kinase involved in cell cycle, nuclear
CC condensation and transcription regulation (PubMed:14645249,
CC PubMed:9521809, PubMed:33076429). Involved in Golgi disassembly during
CC the cell cycle: following phosphorylation by PLK3 during mitosis,
CC required to induce Golgi fragmentation (By similarity). Phosphorylates
CC 'Thr-18' of p53/TP53 and may thereby prevent the interaction between
CC p53/TP53 and MDM2 (By similarity). Phosphorylates KAT5 in response to
CC DNA damage, promoting KAT5 association with chromatin and histone
CC acetyltransferase activity (PubMed:33076429). Phosphorylates BANF1:
CC disrupts its ability to bind DNA, reduces its binding to LEM domain-
CC containing proteins and causes its relocalization from the nucleus to
CC the cytoplasm (By similarity). Phosphorylates ATF2 which activates its
CC transcriptional activity (By similarity).
CC {ECO:0000250|UniProtKB:Q99986, ECO:0000269|PubMed:14645249,
CC ECO:0000269|PubMed:33076429, ECO:0000269|PubMed:9521809}.
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:14645249};
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:14645249};
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+). Has a higher affinity for
CC Mn(2+) than for Mg(2+). RAN inhibits its autophosphorylation and its
CC ability to phosphorylate histone H3 (By similarity).
CC {ECO:0000250|UniProtKB:Q99986}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:14645249,
CC ECO:0000269|PubMed:9521809}. Cytoplasm {ECO:0000250|UniProtKB:Q99986}.
CC Note=Dispersed throughout the cell but not located on mitotic spindle
CC or chromatids during mitosis.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=4;
CC Name=1; Synonyms=L;
CC IsoId=Q80X41-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q80X41-2; Sequence=VSP_008529;
CC Name=3; Synonyms=S;
CC IsoId=Q80X41-3; Sequence=VSP_008532;
CC Name=5;
CC IsoId=Q80X41-5; Sequence=VSP_008528, VSP_008532;
CC -!- TISSUE SPECIFICITY: Highly expressed in testis. Expressed in liver,
CC kidney and muscle. Weakly expressed in thymus, bone marrow and spleen.
CC {ECO:0000269|PubMed:12782311, ECO:0000269|PubMed:9521809}.
CC -!- DEVELOPMENTAL STAGE: Expressed from 10.5 dpc to 14 dpc in developing
CC liver and then decreases. It increases again from 17.5 dpc and remains
CC thereafter. Highly expressed in hematopoietic embryonic tissues from
CC 10.5 dpc to 14.5 dpc. Weakly expressed in the yolk-sac.
CC {ECO:0000269|PubMed:12782311}.
CC -!- PTM: Autophosphorylated at various serine and threonine residues
CC (PubMed:14645249). Autophosphorylation does not impair its ability to
CC phosphorylate p53/TP53 (By similarity). Phosphorylation by PLK3 leads
CC to induction of Golgi fragmentation during mitosis (By similarity).
CC {ECO:0000250|UniProtKB:Q99986, ECO:0000269|PubMed:14645249}.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. CK1 Ser/Thr
CC protein kinase family. VRK subfamily. {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; AF080252; AAC29496.1; -; mRNA.
DR EMBL; AF080253; AAC29497.1; -; mRNA.
DR EMBL; AK032344; BAC27825.1; -; mRNA.
DR EMBL; AK088230; BAC40225.1; -; mRNA.
DR EMBL; AK088674; BAC40497.1; -; mRNA.
DR EMBL; BC016676; AAH16676.1; -; mRNA.
DR CCDS; CCDS26157.1; -. [Q80X41-3]
DR CCDS; CCDS26158.1; -. [Q80X41-2]
DR CCDS; CCDS36551.1; -. [Q80X41-1]
DR RefSeq; NP_001025014.1; NM_001029843.1. [Q80X41-3]
DR RefSeq; NP_001025015.1; NM_001029844.1. [Q80X41-2]
DR RefSeq; NP_035835.1; NM_011705.3. [Q80X41-1]
DR RefSeq; XP_006515872.1; XM_006515809.2. [Q80X41-1]
DR RefSeq; XP_006515873.1; XM_006515810.3. [Q80X41-1]
DR RefSeq; XP_006515874.1; XM_006515811.3. [Q80X41-1]
DR RefSeq; XP_006515875.1; XM_006515812.2.
DR RefSeq; XP_017170535.1; XM_017315046.1.
DR AlphaFoldDB; Q80X41; -.
DR SMR; Q80X41; -.
DR BioGRID; 204536; 6.
DR IntAct; Q80X41; 3.
DR MINT; Q80X41; -.
DR STRING; 10090.ENSMUSP00000021539; -.
DR iPTMnet; Q80X41; -.
DR PhosphoSitePlus; Q80X41; -.
DR EPD; Q80X41; -.
DR MaxQB; Q80X41; -.
DR PaxDb; Q80X41; -.
DR PRIDE; Q80X41; -.
DR ProteomicsDB; 299728; -. [Q80X41-1]
DR ProteomicsDB; 299729; -. [Q80X41-2]
DR ProteomicsDB; 299730; -. [Q80X41-3]
DR ProteomicsDB; 299731; -. [Q80X41-5]
DR Antibodypedia; 42; 273 antibodies from 36 providers.
DR DNASU; 22367; -.
DR Ensembl; ENSMUST00000021539; ENSMUSP00000021539; ENSMUSG00000021115. [Q80X41-1]
DR Ensembl; ENSMUST00000072040; ENSMUSP00000071922; ENSMUSG00000021115. [Q80X41-2]
DR Ensembl; ENSMUST00000085026; ENSMUSP00000082101; ENSMUSG00000021115. [Q80X41-3]
DR Ensembl; ENSMUST00000220629; ENSMUSP00000152109; ENSMUSG00000021115. [Q80X41-1]
DR GeneID; 22367; -.
DR KEGG; mmu:22367; -.
DR UCSC; uc007ozb.1; mouse. [Q80X41-1]
DR UCSC; uc007ozd.1; mouse. [Q80X41-2]
DR UCSC; uc007oze.1; mouse. [Q80X41-5]
DR CTD; 7443; -.
DR MGI; MGI:1261847; Vrk1.
DR VEuPathDB; HostDB:ENSMUSG00000021115; -.
DR eggNOG; KOG1164; Eukaryota.
DR GeneTree; ENSGT00940000155554; -.
DR HOGENOM; CLU_019279_4_0_1; -.
DR InParanoid; Q80X41; -.
DR OMA; PDYDKCR; -.
DR OrthoDB; 866200at2759; -.
DR PhylomeDB; Q80X41; -.
DR TreeFam; TF106473; -.
DR Reactome; R-MMU-2995383; Initiation of Nuclear Envelope (NE) Reformation.
DR BioGRID-ORCS; 22367; 25 hits in 72 CRISPR screens.
DR ChiTaRS; Vrk1; mouse.
DR PRO; PR:Q80X41; -.
DR Proteomes; UP000000589; Chromosome 12.
DR RNAct; Q80X41; protein.
DR Bgee; ENSMUSG00000021115; Expressed in granulocyte and 223 other tissues.
DR ExpressionAtlas; Q80X41; baseline and differential.
DR Genevisible; Q80X41; MM.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005829; C:cytosol; ISO:MGI.
DR GO; GO:0005795; C:Golgi stack; ISS:UniProtKB.
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:UniProtKB-KW.
DR GO; GO:0042393; F:histone binding; ISO:MGI.
DR GO; GO:0035175; F:histone kinase activity (H3-S10 specific); ISO:MGI.
DR GO; GO:0072354; F:histone kinase activity (H3-T3 specific); ISO:MGI.
DR GO; GO:0004672; F:protein kinase activity; ISO:MGI.
DR GO; GO:0019901; F:protein kinase binding; ISO: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:0007049; P:cell cycle; IEA:UniProtKB-KW.
DR GO; GO:0051301; P:cell division; IEA:UniProtKB-KW.
DR GO; GO:0006974; P:cellular response to DNA damage stimulus; ISS:UniProtKB.
DR GO; GO:0090166; P:Golgi disassembly; ISS:UniProtKB.
DR GO; GO:0016572; P:histone phosphorylation; IBA:GO_Central.
DR GO; GO:0018105; P:peptidyl-serine phosphorylation; IBA:GO_Central.
DR GO; GO:0120187; P:positive regulation of protein localization to chromatin; ISS:UniProtKB.
DR GO; GO:0046777; P:protein autophosphorylation; IDA:MGI.
DR GO; GO:0006468; P:protein phosphorylation; IDA:MGI.
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 Alternative splicing; ATP-binding; Cell cycle; Cell division; Cytoplasm;
KW Direct protein sequencing; Isopeptide bond; Kinase; Mitosis;
KW Nucleotide-binding; Nucleus; Phosphoprotein; Reference proteome;
KW Serine/threonine-protein kinase; Transferase; Ubl conjugation.
FT CHAIN 1..440
FT /note="Serine/threonine-protein kinase VRK1"
FT /id="PRO_0000086804"
FT DOMAIN 37..317
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT REGION 379..440
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 379..415
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 416..430
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:0000250|UniProtKB:Q99986"
FT MOD_RES 376
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q99986"
FT MOD_RES 378
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q99986"
FT CROSSLNK 71
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0000250|UniProtKB:Q99986"
FT VAR_SEQ 125..126
FT /note="Missing (in isoform 5)"
FT /evidence="ECO:0000303|PubMed:16141072"
FT /id="VSP_008528"
FT VAR_SEQ 388..431
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_008529"
FT VAR_SEQ 388..411
FT /note="Missing (in isoform 3 and isoform 5)"
FT /evidence="ECO:0000303|PubMed:16141072,
FT ECO:0000303|PubMed:9521809"
FT /id="VSP_008532"
FT MUTAGEN 179
FT /note="K->E: Abolished protein serine/threonine kinase
FT activity."
FT /evidence="ECO:0000269|PubMed:33076429"
SQ SEQUENCE 440 AA; 49741 MW; 8318BA76A44B16BF CRC64;
MPRVKAAQAG RPGPAKRRLA EQFAAGEVLT DMSRKEWKLG LPIGQGGFGC IYLADTNSSK
PVGSDAPCVV KVEPSDNGPL FTELKFYQRA AKPEQIQKWI RTHKLKYLGV PKYWGSGLHD
KNGKSYRFMI MDRFGSDLQK IYEANAKRFS RKTVLQLSLR ILDILEYIHE HEYVHGDIKA
SNLLLSHKNP DQVYLVDYGL AYRYCPDGVH KEYKEDPKRC HDGTLEFTSI DAHKGVAPSR
RGDLEILGYC MIQWLSGCLP WEDNLKDPNY VRDSKIRYRD NVAALMEKCF PEKNKPGEIA
KYMESVKLLE YTEKPLYQNL RDILLQGLKA IGSKDDGKLD FSAVENGSVK TRPASKKRKK
EAEESAVCAV EDMECSDTQV QEAAQTRSVE SQGAIHGSMS QPAAGCSSSD SSRRQQHLGL
EQDMLRLDRR GSRTRKKAQK
