ID VRK2_HUMAN Reviewed; 508 AA. AC Q86Y07; B4DKL0; D6W5D4; D6W5D6; Q49AK9; Q53EU9; Q53S39; Q53S77; Q53TU1; AC Q86Y08; Q86Y09; Q86Y10; Q86Y11; Q86Y12; Q8IXI5; Q99987; DT 10-OCT-2003, integrated into UniProtKB/Swiss-Prot. DT 07-MAR-2006, sequence version 3. DT 07-APR-2021, entry version 194. DE RecName: Full=Serine/threonine-protein kinase VRK2; DE EC=2.7.11.1; DE AltName: Full=Vaccinia-related kinase 2; GN Name=VRK2; 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), TISSUE SPECIFICITY, AND VARIANT RP VAL-167. RC TISSUE=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 [MRNA] (ISOFORM 2), IDENTIFICATION (ISOFORM 1), RP FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, AUTOPHOSPHORYLATION, RP AND VARIANT VAL-167. 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 [3] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1; 3; 4 AND 5). RA Suriyapperuma S.P., Sarfarazi M.; RT "Identification of 6 different isoforms for Vaccinia-related kinase 2 RT (VRK2) gene."; RL Submitted (JAN-2003) to the EMBL/GenBank/DDBJ databases. RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 4). RC TISSUE=Colon; 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 [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RC TISSUE=Testis; RA Totoki Y., Toyoda A., Takeda T., Sakaki Y., Tanaka A., Yokoyama S.; RL Submitted (APR-2005) to the EMBL/GenBank/DDBJ databases. RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=15815621; DOI=10.1038/nature03466; RA Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P., RA Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C., RA Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L., RA Du H., Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A., RA Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J., RA Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M., RA Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T., RA Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S., RA Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K., RA McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C., RA Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S., RA Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C., RA Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M., RA Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C., RA Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J., RA Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E., RA Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X., RA Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M., RA Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C., RA Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S., RA Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H., RA Wilson R.K.; RT "Generation and annotation of the DNA sequences of human chromosomes 2 and RT 4."; RL Nature 434:724-731(2005). RN [7] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., RA Hunkapiller M.W., Myers E.W., Venter J.C.; RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases. RN [8] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANT VAL-167. 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 [9] RP FUNCTION, SUBCELLULAR LOCATION, AND AUTOPHOSPHORYLATION. 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 [10] RP INTERACTION WITH EPSTEIN-BARR VIRUS BHRF1 (MICROBIAL INFECTION). RX PubMed=16963744; DOI=10.1099/vir.0.81953-0; RA Li L.Y., Liu M.Y., Shih H.M., Tsai C.H., Chen J.Y.; RT "Human cellular protein VRK2 interacts specifically with Epstein-Barr virus RT BHRF1, a homologue of Bcl-2, and enhances cell survival."; RL J. Gen. Virol. 87:2869-2878(2006). RN [11] 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 [12] RP FUNCTION, AND INTERACTION WITH MAP3K7. RX PubMed=17709393; DOI=10.1128/mcb.00025-07; RA Blanco S., Santos C., Lazo P.A.; RT "Vaccinia-related kinase 2 modulates the stress response to hypoxia RT mediated by TAK1."; RL Mol. Cell. Biol. 27:7273-7283(2007). RN [13] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-336, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=18691976; DOI=10.1016/j.molcel.2008.07.007; RA Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R., RA Greff Z., Keri G., Stemmann O., Mann M.; RT "Kinase-selective enrichment enables quantitative phosphoproteomics of the RT kinome across the cell cycle."; RL Mol. Cell 31:438-448(2008). RN [14] 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 [15] RP FUNCTION, SUBCELLULAR LOCATION, AND INTERACTION WITH MAPK8IP1; MAPK3K7 AND RP MAP2K7. RX PubMed=18286207; DOI=10.1371/journal.pone.0001660; RA Blanco S., Sanz-Garcia M., Santos C.R., Lazo P.A.; RT "Modulation of interleukin-1 transcriptional response by the interaction RT between VRK2 and the JIP1 scaffold protein."; RL PLoS ONE 3:E1660-E1660(2008). RN [16] 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 [17] RP FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH MAP2K1 AND KSR1, AND RP TISSUE SPECIFICITY. RX PubMed=20679487; DOI=10.1128/mcb.01581-09; RA Fernandez I.F., Blanco S., Lozano J., Lazo P.A.; RT "VRK2 inhibits mitogen-activated protein kinase signaling and inversely RT correlates with ErbB2 in human breast cancer."; RL Mol. Cell. Biol. 30:4687-4697(2010). RN [18] 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 [19] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-406, AND IDENTIFICATION BY RP 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 [20] RP X-RAY CRYSTALLOGRAPHY (1.7 ANGSTROMS) OF 14-335. 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 [21] RP VARIANTS [LARGE SCALE ANALYSIS] ASP-50; MET-157 AND VAL-167. 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: Serine/threonine kinase that regulates several signal CC transduction pathways. Isoform 1 modulates the stress response to CC hypoxia and cytokines, such as interleukin-1 beta (IL1B) and this is CC dependent on its interaction with MAPK8IP1, which assembles mitogen- CC activated protein kinase (MAPK) complexes. Inhibition of signal CC transmission mediated by the assembly of MAPK8IP1-MAPK complexes CC reduces JNK phosphorylation and JUN-dependent transcription. CC Phosphorylates 'Thr-18' of p53/TP53, histone H3, and may also CC phosphorylate MAPK8IP1. Phosphorylates BANF1 and disrupts its ability CC to bind DNA and reduces its binding to LEM domain-containing proteins. CC Downregulates the transactivation of transcription induced by ERBB2, CC HRAS, BRAF, and MEK1. Blocks the phosphorylation of ERK in response to CC ERBB2 and HRAS. Can also phosphorylate the following substrates that CC are commonly used to establish in vitro kinase activity: casein, MBP CC and histone H2B, but it is not sure that this is physiologically CC relevant. CC -!- FUNCTION: Isoform 2 phosphorylates 'Thr-18' of p53/TP53, as well as CC histone H3. Reduces p53/TP53 ubiquitination by MDM2, promotes p53/TP53 CC acetylation by EP300 and thereby increases p53/TP53 stability and CC activity. 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 -!- 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; CC -!- ACTIVITY REGULATION: RAN inhibits its autophosphorylation and its CC ability to phosphorylate histone H3. {ECO:0000269|PubMed:18617507}. CC -!- SUBUNIT: Isoform 1 interacts with MAP3K7, MAP2K7, MAP2K1 and KSR1. CC Isoform 1 and isoform 2 interact with RAN and MAPK8IP1. CC {ECO:0000269|PubMed:17709393, ECO:0000269|PubMed:18286207, CC ECO:0000269|PubMed:18617507, ECO:0000269|PubMed:20679487}. CC -!- SUBUNIT: (Microbial infection) Isoform 1 interacts with Epstein-Barr CC virus BHRF1; this interaction is involved in protecting cells from CC apoptosis. {ECO:0000269|PubMed:16963744}. CC -!- INTERACTION: CC Q86Y07; Q13520: AQP6; NbExp=3; IntAct=EBI-1207615, EBI-13059134; CC Q86Y07; P36382: GJA5; NbExp=3; IntAct=EBI-1207615, EBI-750433; CC Q86Y07; Q8IVT5: KSR1; NbExp=4; IntAct=EBI-1207615, EBI-486984; CC Q86Y07; Q02750: MAP2K1; NbExp=2; IntAct=EBI-1207615, EBI-492564; CC Q86Y07; Q8N4V1: MMGT1; NbExp=3; IntAct=EBI-1207615, EBI-6163737; CC Q86Y07; Q0VAB0: TBXA2R; NbExp=3; IntAct=EBI-1207615, EBI-18271435; CC Q86Y07; Q9NUH8: TMEM14B; NbExp=3; IntAct=EBI-1207615, EBI-8638294; CC Q86Y07; Q6UW68: TMEM205; NbExp=3; IntAct=EBI-1207615, EBI-6269551; CC Q86Y07; Q6PEY1: TMEM88; NbExp=3; IntAct=EBI-1207615, EBI-17198826; CC Q86Y07; P03182: BHRF1; Xeno; NbExp=7; IntAct=EBI-1207615, EBI-1207659; CC Q86Y07-1; Q07817-1: BCL2L1; NbExp=2; IntAct=EBI-1207633, EBI-287195; CC Q86Y07-1; Q02750: MAP2K1; NbExp=2; IntAct=EBI-1207633, EBI-492564; CC Q86Y07-1; Q13469: NFATC2; NbExp=3; IntAct=EBI-1207633, EBI-716258; CC Q86Y07-1; P62826: RAN; NbExp=2; IntAct=EBI-1207633, EBI-286642; CC Q86Y07-1; Q61097: Ksr1; Xeno; NbExp=8; IntAct=EBI-1207633, EBI-1536336; CC Q86Y07-1; Q62073: Map3k7; Xeno; NbExp=3; IntAct=EBI-1207633, EBI-1775345; CC Q86Y07-1; Q60591: Nfatc2; Xeno; NbExp=2; IntAct=EBI-1207633, EBI-643104; CC Q86Y07-1; Q8CF89: Tab1; Xeno; NbExp=2; IntAct=EBI-1207633, EBI-1778503; CC Q86Y07-2; Q13469: NFATC2; NbExp=4; IntAct=EBI-1207636, EBI-716258; CC Q86Y07-2; Q9WVI9-2: Mapk8ip1; Xeno; NbExp=2; IntAct=EBI-1207636, EBI-288464; CC Q86Y07-5; P62826: RAN; NbExp=2; IntAct=EBI-1207649, EBI-286642; CC -!- SUBCELLULAR LOCATION: [Isoform 1]: Cytoplasm. Endoplasmic reticulum CC membrane {ECO:0000269|PubMed:16704422}; Single-pass type IV membrane CC protein {ECO:0000255}. Mitochondrion membrane CC {ECO:0000269|PubMed:16704422}; Single-pass type IV membrane protein CC {ECO:0000255}. Nucleus envelope {ECO:0000250|UniProtKB:Q8BN21}. CC -!- SUBCELLULAR LOCATION: [Isoform 2]: Cytoplasm CC {ECO:0000269|PubMed:16704422}. Nucleus {ECO:0000269|PubMed:16704422}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=5; CC Name=1; Synonyms=VRK2A; CC IsoId=Q86Y07-1; Sequence=Displayed; CC Name=2; Synonyms=VRK2B; CC IsoId=Q86Y07-2; Sequence=VSP_008537, VSP_008538; CC Name=3; CC IsoId=Q86Y07-3; Sequence=VSP_008533; CC Name=4; Synonyms=5; CC IsoId=Q86Y07-4; Sequence=VSP_008534; CC Name=5; Synonyms=6; CC IsoId=Q86Y07-5; Sequence=VSP_008535, VSP_008536; CC -!- TISSUE SPECIFICITY: Isoform 1 and isoform 2 are expressed in various CC tumor cell lines. Expression of isoform 1 inversely correlates with CC ERBB2 in breast carcinomas (at protein level). Widely expressed. Highly CC expressed in fetal liver, skeletal muscle, pancreas, heart, peripheral CC blood leukocytes and testis. {ECO:0000269|PubMed:16704422, CC ECO:0000269|PubMed:20679487, ECO:0000269|PubMed:9344656}. CC -!- PTM: Isoform 1 and isoform 2 are autophosphorylated. CC -!- SIMILARITY: Belongs to the protein kinase superfamily. CK1 Ser/Thr CC protein kinase family. VRK subfamily. {ECO:0000305}. CC -!- SEQUENCE CAUTION: CC Sequence=CAD54446.2; Type=Miscellaneous discrepancy; Note=Aberrant splicing.; Evidence={ECO:0000305}; CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and CC Haematology; CC URL="http://atlasgeneticsoncology.org/Genes/VRK2ID42799ch2p16.html"; 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; AB000450; BAA19109.1; -; mRNA. DR EMBL; AJ512204; CAD54446.2; ALT_SEQ; mRNA. DR EMBL; AY228367; AAO73047.1; -; mRNA. DR EMBL; AY228368; AAO73048.1; -; mRNA. DR EMBL; AY228369; AAO73049.1; -; mRNA. DR EMBL; AY228370; AAO73050.1; -; mRNA. DR EMBL; AY228371; AAO73051.1; -; mRNA. DR EMBL; AY228372; AAO73052.1; -; mRNA. DR EMBL; AK296611; BAG59222.1; -; mRNA. DR EMBL; AK223540; BAD97260.1; -; mRNA. DR EMBL; AC007250; AAY15019.1; -; Genomic_DNA. DR EMBL; AC068193; AAX93262.1; -; Genomic_DNA. DR EMBL; AC073215; AAY14648.1; -; Genomic_DNA. DR EMBL; CH471053; EAX00062.1; -; Genomic_DNA. DR EMBL; CH471053; EAX00064.1; -; Genomic_DNA. DR EMBL; CH471053; EAX00066.1; -; Genomic_DNA. DR EMBL; CH471053; EAX00067.1; -; Genomic_DNA. DR EMBL; CH471053; EAX00068.1; -; Genomic_DNA. DR EMBL; BC027854; AAH27854.1; -; mRNA. DR CCDS; CCDS1859.1; -. [Q86Y07-1] DR CCDS; CCDS46291.1; -. [Q86Y07-5] DR CCDS; CCDS46292.1; -. [Q86Y07-3] DR RefSeq; NP_001123952.1; NM_001130480.2. [Q86Y07-1] DR RefSeq; NP_001123953.1; NM_001130481.2. [Q86Y07-1] DR RefSeq; NP_001123954.1; NM_001130482.2. [Q86Y07-3] DR RefSeq; NP_001123955.1; NM_001130483.2. [Q86Y07-5] DR RefSeq; NP_001275765.1; NM_001288836.1. [Q86Y07-4] DR RefSeq; NP_001275766.1; NM_001288837.1. [Q86Y07-1] DR RefSeq; NP_001275767.1; NM_001288838.1. [Q86Y07-5] DR RefSeq; NP_001275768.1; NM_001288839.1. [Q86Y07-4] DR RefSeq; NP_006287.2; NM_006296.6. [Q86Y07-1] DR RefSeq; XP_005264597.1; XM_005264540.4. [Q86Y07-1] DR RefSeq; XP_006712153.1; XM_006712090.3. [Q86Y07-2] DR RefSeq; XP_006712154.1; XM_006712091.3. [Q86Y07-5] DR RefSeq; XP_006712155.1; XM_006712092.3. [Q86Y07-4] DR RefSeq; XP_006712156.1; XM_006712093.3. [Q86Y07-4] DR RefSeq; XP_011531394.1; XM_011533092.2. [Q86Y07-1] DR RefSeq; XP_016860347.1; XM_017004858.1. [Q86Y07-2] DR RefSeq; XP_016860348.1; XM_017004859.1. [Q86Y07-4] DR RefSeq; XP_016860349.1; XM_017004860.1. [Q86Y07-4] DR RefSeq; XP_016860350.1; XM_017004861.1. [Q86Y07-4] DR RefSeq; XP_016860351.1; XM_017004862.1. [Q86Y07-4] DR RefSeq; XP_016860352.1; XM_017004863.1. [Q86Y07-4] DR PDB; 2V62; X-ray; 1.70 A; A/B=14-335. DR PDB; 5UU1; X-ray; 2.00 A; A=14-335. DR PDB; 6NCG; X-ray; 2.45 A; A/B=14-335. DR PDBsum; 2V62; -. DR PDBsum; 5UU1; -. DR PDBsum; 6NCG; -. DR SMR; Q86Y07; -. DR BioGRID; 113283; 80. DR IntAct; Q86Y07; 49. DR STRING; 9606.ENSP00000408002; -. DR BindingDB; Q86Y07; -. DR ChEMBL; CHEMBL1649059; -. DR DrugCentral; Q86Y07; -. DR iPTMnet; Q86Y07; -. DR PhosphoSitePlus; Q86Y07; -. DR BioMuta; VRK2; -. DR DMDM; 90116515; -. DR EPD; Q86Y07; -. DR jPOST; Q86Y07; -. DR MassIVE; Q86Y07; -. DR MaxQB; Q86Y07; -. DR PaxDb; Q86Y07; -. DR PeptideAtlas; Q86Y07; -. DR PRIDE; Q86Y07; -. DR ProteomicsDB; 70345; -. [Q86Y07-1] DR ProteomicsDB; 70346; -. [Q86Y07-2] DR ProteomicsDB; 70347; -. [Q86Y07-3] DR ProteomicsDB; 70348; -. [Q86Y07-4] DR ProteomicsDB; 70349; -. [Q86Y07-5] DR Antibodypedia; 30474; 201 antibodies. DR DNASU; 7444; -. DR Ensembl; ENST00000340157; ENSP00000342381; ENSG00000028116. [Q86Y07-1] DR Ensembl; ENST00000412104; ENSP00000404156; ENSG00000028116. [Q86Y07-4] DR Ensembl; ENST00000417641; ENSP00000402375; ENSG00000028116. [Q86Y07-5] DR Ensembl; ENST00000435505; ENSP00000408002; ENSG00000028116. [Q86Y07-1] DR Ensembl; ENST00000440705; ENSP00000398323; ENSG00000028116. [Q86Y07-3] DR Ensembl; ENST00000648897; ENSP00000497378; ENSG00000028116. [Q86Y07-2] DR GeneID; 7444; -. DR KEGG; hsa:7444; -. DR UCSC; uc002rzo.3; human. [Q86Y07-1] DR CTD; 7444; -. DR DisGeNET; 7444; -. DR GeneCards; VRK2; -. DR HGNC; HGNC:12719; VRK2. DR HPA; ENSG00000028116; Low tissue specificity. DR MIM; 602169; gene. DR neXtProt; NX_Q86Y07; -. DR OpenTargets; ENSG00000028116; -. DR PharmGKB; PA37331; -. DR VEuPathDB; HostDB:ENSG00000028116.16; -. DR eggNOG; KOG1164; Eukaryota. DR GeneTree; ENSGT00940000158042; -. DR HOGENOM; CLU_019279_4_3_1; -. DR InParanoid; Q86Y07; -. DR OMA; YLVCAHN; -. DR OrthoDB; 866200at2759; -. DR PhylomeDB; Q86Y07; -. DR TreeFam; TF106473; -. DR PathwayCommons; Q86Y07; -. DR Reactome; R-HSA-2980766; Nuclear Envelope Breakdown. [Q86Y07-2] DR Reactome; R-HSA-2995383; Initiation of Nuclear Envelope (NE) Reformation. [Q86Y07-2] DR SignaLink; Q86Y07; -. DR SIGNOR; Q86Y07; -. DR BioGRID-ORCS; 7444; 7 hits in 1030 CRISPR screens. DR ChiTaRS; VRK2; human. DR EvolutionaryTrace; Q86Y07; -. DR GeneWiki; VRK2; -. DR GenomeRNAi; 7444; -. DR Pharos; Q86Y07; Tbio. DR PRO; PR:Q86Y07; -. DR Proteomes; UP000005640; Chromosome 2. DR RNAct; Q86Y07; protein. DR Bgee; ENSG00000028116; Expressed in corpus callosum and 234 other tissues. DR ExpressionAtlas; Q86Y07; baseline and differential. DR Genevisible; Q86Y07; HS. DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB. DR GO; GO:0005783; C:endoplasmic reticulum; IDA:HPA. DR GO; GO:0005789; C:endoplasmic reticulum membrane; IDA:UniProtKB. DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW. DR GO; GO:0031966; C:mitochondrial membrane; IDA:UniProtKB. DR GO; GO:0005635; C:nuclear envelope; ISS:UniProtKB. DR GO; GO:0005634; C:nucleus; IDA:UniProtKB. DR GO; GO:0032991; C:protein-containing complex; IDA:MGI. DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW. DR GO; GO:0019904; F:protein domain specific binding; IDA:MGI. DR GO; GO:0019901; F:protein kinase binding; IDA:MGI. DR GO; GO:0106310; F:protein serine kinase activity; IEA:UniProtKB-EC. DR GO; GO:0004674; F:protein serine/threonine kinase activity; IDA:UniProtKB. DR GO; GO:0106311; F:protein threonine kinase activity; IEA:UniProtKB-EC. DR GO; GO:0034599; P:cellular response to oxidative stress; IMP:UniProtKB. DR GO; GO:0018105; P:peptidyl-serine phosphorylation; IBA:GO_Central. DR GO; GO:0046777; P:protein autophosphorylation; IDA:UniProtKB. DR GO; GO:0006468; P:protein phosphorylation; TAS:ProtInc. DR GO; GO:2000659; P:regulation of interleukin-1-mediated signaling pathway; IMP:UniProtKB. DR GO; GO:0043408; P:regulation of MAPK cascade; IMP:UniProtKB. DR GO; GO:0016032; P:viral process; IEA:UniProtKB-KW. DR InterPro; IPR011009; Kinase-like_dom_sf. DR InterPro; IPR000719; Prot_kinase_dom. 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; PS50011; PROTEIN_KINASE_DOM; 1. DR PROSITE; PS00108; PROTEIN_KINASE_ST; 1. PE 1: Evidence at protein level; KW 3D-structure; Alternative splicing; ATP-binding; Cytoplasm; KW Endoplasmic reticulum; Host-virus interaction; Kinase; Membrane; KW Mitochondrion; Nucleotide-binding; Nucleus; Phosphoprotein; KW Reference proteome; Serine/threonine-protein kinase; Transferase; KW Transmembrane; Transmembrane helix. FT CHAIN 1..508 FT /note="Serine/threonine-protein kinase VRK2" FT /id="PRO_0000086806" FT TRANSMEM 487..507 FT /note="Helical; Anchor for type IV membrane protein" FT /evidence="ECO:0000255" FT DOMAIN 29..319 FT /note="Protein kinase" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159" FT NP_BIND 35..43 FT /note="ATP" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159" FT REGION 397..508 FT /note="Interaction with MAP3K7" FT /evidence="ECO:0000269|PubMed:17709393" FT ACT_SITE 166 FT /note="Proton acceptor" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159, FT ECO:0000255|PROSITE-ProRule:PRU10027" FT BINDING 61 FT /note="ATP" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159" FT MOD_RES 336 FT /note="Phosphothreonine" FT /evidence="ECO:0007744|PubMed:18691976" FT MOD_RES 406 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163" FT VAR_SEQ 1..118 FT /note="Missing (in isoform 4)" FT /evidence="ECO:0000303|PubMed:14702039, ECO:0000303|Ref.3" FT /id="VSP_008534" FT VAR_SEQ 1..23 FT /note="Missing (in isoform 3)" FT /evidence="ECO:0000303|Ref.3" FT /id="VSP_008533" FT VAR_SEQ 395..397 FT /note="EST -> VEA (in isoform 2)" FT /evidence="ECO:0000303|PubMed:16704422" FT /id="VSP_008537" FT VAR_SEQ 395..396 FT /note="ES -> FR (in isoform 5)" FT /evidence="ECO:0000303|Ref.3" FT /id="VSP_008535" FT VAR_SEQ 397..508 FT /note="Missing (in isoform 5)" FT /evidence="ECO:0000303|Ref.3" FT /id="VSP_008536" FT VAR_SEQ 398..508 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000303|PubMed:16704422" FT /id="VSP_008538" FT VARIANT 50 FT /note="N -> D (in dbSNP:rs34130684)" FT /evidence="ECO:0000269|PubMed:17344846" FT /id="VAR_041293" FT VARIANT 157 FT /note="I -> M (in dbSNP:rs35966666)" FT /evidence="ECO:0000269|PubMed:17344846" FT /id="VAR_041294" FT VARIANT 167 FT /note="I -> V (in dbSNP:rs1051061)" FT /evidence="ECO:0000269|PubMed:15489334, FT ECO:0000269|PubMed:16704422, ECO:0000269|PubMed:17344846, FT ECO:0000269|PubMed:9344656" FT /id="VAR_017095" FT VARIANT 211 FT /note="N -> S (in dbSNP:rs36081172)" FT /id="VAR_051681" FT CONFLICT 419 FT /note="K -> E (in Ref. 3; AAO73048/AAO73049/AAO73051)" FT /evidence="ECO:0000305" FT STRAND 20..22 FT /evidence="ECO:0007744|PDB:2V62" FT STRAND 28..34 FT /evidence="ECO:0007744|PDB:2V62" FT STRAND 43..51 FT /evidence="ECO:0007744|PDB:2V62" FT HELIX 53..55 FT /evidence="ECO:0007744|PDB:2V62" FT STRAND 58..64 FT /evidence="ECO:0007744|PDB:2V62" FT STRAND 65..67 FT /evidence="ECO:0007744|PDB:5UU1" FT HELIX 69..80 FT /evidence="ECO:0007744|PDB:2V62" FT HELIX 83..93 FT /evidence="ECO:0007744|PDB:2V62" FT STRAND 103..113 FT /evidence="ECO:0007744|PDB:2V62" FT STRAND 115..122 FT /evidence="ECO:0007744|PDB:2V62" FT STRAND 124..127 FT /evidence="ECO:0007744|PDB:2V62" FT HELIX 128..131 FT /evidence="ECO:0007744|PDB:2V62" FT HELIX 134..136 FT /evidence="ECO:0007744|PDB:2V62" FT HELIX 140..159 FT /evidence="ECO:0007744|PDB:2V62" FT HELIX 169..171 FT /evidence="ECO:0007744|PDB:2V62" FT STRAND 172..178 FT /evidence="ECO:0007744|PDB:2V62" FT STRAND 181..184 FT /evidence="ECO:0007744|PDB:2V62" FT HELIX 187..189 FT /evidence="ECO:0007744|PDB:6NCG" FT STRAND 191..194 FT /evidence="ECO:0007744|PDB:2V62" FT HELIX 195..197 FT /evidence="ECO:0007744|PDB:2V62" FT HELIX 206..208 FT /evidence="ECO:0007744|PDB:2V62" FT TURN 214..216 FT /evidence="ECO:0007744|PDB:2V62" FT HELIX 219..223 FT /evidence="ECO:0007744|PDB:2V62" FT HELIX 229..245 FT /evidence="ECO:0007744|PDB:2V62" FT HELIX 251..253 FT /evidence="ECO:0007744|PDB:2V62" FT HELIX 257..269 FT /evidence="ECO:0007744|PDB:2V62" FT TURN 270..272 FT /evidence="ECO:0007744|PDB:2V62" FT HELIX 273..278 FT /evidence="ECO:0007744|PDB:2V62" FT HELIX 286..296 FT /evidence="ECO:0007744|PDB:2V62" FT HELIX 306..313 FT /evidence="ECO:0007744|PDB:2V62" SQ SEQUENCE 508 AA; 58141 MW; 9F3F6FCC9280568F CRC64; MPPKRNEKYK LPIPFPEGKV LDDMEGNQWV LGKKIGSGGF GLIYLAFPTN KPEKDARHVV KVEYQENGPL FSELKFYQRV AKKDCIKKWI ERKQLDYLGI PLFYGSGLTE FKGRSYRFMV MERLGIDLQK ISGQNGTFKK STVLQLGIRM LDVLEYIHEN EYVHGDIKAA NLLLGYKNPD QVYLADYGLS YRYCPNGNHK QYQENPRKGH NGTIEFTSLD AHKGVALSRR SDVEILGYCM LRWLCGKLPW EQNLKDPVAV QTAKTNLLDE LPQSVLKWAP SGSSCCEIAQ FLVCAHSLAY DEKPNYQALK KILNPHGIPL GPLDFSTKGQ SINVHTPNSQ KVDSQKAATK QVNKAHNRLI EKKVHSERSA ESCATWKVQK EEKLIGLMNN EAAQESTRRR QKYQESQEPL NEVNSFPQKI SYTQFPNSFY EPHQDFTSPD IFKKSRSPSW YKYTSTVSTG ITDLESSTGL WPTISQFTLS EETNADVYYY RIIIPVLLML VFLALFFL //