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 27-MAR-2024, entry version 172. 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.ENSMUSP00000152109; -. DR iPTMnet; Q80X41; -. DR PhosphoSitePlus; Q80X41; -. DR SwissPalm; Q80X41; -. DR EPD; Q80X41; -. DR MaxQB; Q80X41; -. DR PaxDb; 10090-ENSMUSP00000021539; -. DR ProteomicsDB; 299728; -. [Q80X41-1] DR ProteomicsDB; 299729; -. [Q80X41-2] DR ProteomicsDB; 299730; -. [Q80X41-3] DR ProteomicsDB; 299731; -. [Q80X41-5] DR Pumba; Q80X41; -. DR Antibodypedia; 42; 301 antibodies from 36 providers. DR DNASU; 22367; -. DR Ensembl; ENSMUST00000021539.16; ENSMUSP00000021539.9; ENSMUSG00000021115.16. [Q80X41-1] DR Ensembl; ENSMUST00000072040.7; ENSMUSP00000071922.6; ENSMUSG00000021115.16. [Q80X41-2] DR Ensembl; ENSMUST00000085026.12; ENSMUSP00000082101.5; ENSMUSG00000021115.16. [Q80X41-3] DR Ensembl; ENSMUST00000220629.2; ENSMUSP00000152109.2; ENSMUSG00000021115.16. [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 AGR; MGI:1261847; -. 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; MHSTGYV; -. DR OrthoDB; 4064676at2759; -. DR PhylomeDB; Q80X41; -. DR TreeFam; TF106473; -. DR Reactome; R-MMU-2980766; Nuclear Envelope Breakdown. DR Reactome; R-MMU-2995383; Initiation of Nuclear Envelope (NE) Reformation. DR BioGRID-ORCS; 22367; 25 hits in 78 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 226 other cell types or tissues. DR ExpressionAtlas; Q80X41; baseline and differential. 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 H3S10 kinase activity; ISO:MGI. DR GO; GO:0072354; F:histone H3T3 kinase activity; ISO:MGI. DR GO; GO:0016301; F:kinase activity; 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:DNA damage response; ISS:UniProtKB. DR GO; GO:0090166; P:Golgi disassembly; ISS:UniProtKB. DR GO; GO:0016310; P:phosphorylation; IEA:UniProtKB-KW. DR GO; GO:0120187; P:positive regulation of protein localization to chromatin; ISS:UniProtKB. DR GO; GO:0007165; P:signal transduction; IBA:GO_Central. DR CDD; cd14122; STKc_VRK1; 1. 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; IPR017441; Protein_kinase_ATP_BS. DR InterPro; IPR008271; Ser/Thr_kinase_AS. DR PANTHER; PTHR11909; CASEIN KINASE-RELATED; 1. DR PANTHER; PTHR11909:SF78; SERINE_THREONINE-PROTEIN KINASE VRK1; 1. DR Pfam; PF00069; Pkinase; 1. DR SMART; SM00220; S_TKc; 1. DR SUPFAM; SSF56112; Protein kinase-like (PK-like); 1. DR PROSITE; PS00107; PROTEIN_KINASE_ATP; 1. DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 1. DR PROSITE; PS00108; PROTEIN_KINASE_ST; 1. DR Genevisible; Q80X41; MM. 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 //