VRK2_HUMAN
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 03-AUG-2022, entry version 199.
DE RecName: Full=Serine/threonine-protein kinase VRK2;
DE EC=2.7.11.1 {ECO:0000269|PubMed:16495336, ECO:0000269|PubMed:16704422};
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, CATALYTIC ACTIVITY, SUBCELLULAR LOCATION, TISSUE SPECIFICITY,
RP AUTOPHOSPHORYLATION, 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, AND CATALYTIC ACTIVITY.
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 INTERACTION WITH VACCINIA VIRUS PROTEIN B12 (MICROBIAL INFECTION).
RX PubMed=31341052; DOI=10.1128/jvi.00855-19;
RA Rico A.B., Wang Z., Olson A.T., Linville A.C., Bullard B.L., Weaver E.A.,
RA Jones C., Wiebe M.S.;
RT "The Vaccinia Virus (VACV) B1 and Cellular VRK2 Kinases Promote VACV
RT Replication Factory Formation through Phosphorylation-Dependent Inhibition
RT of VACV B12.";
RL J. Virol. 93:0-0(2019).
RN [21]
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 [22]
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 [23]
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 (PubMed:16704422, PubMed:14645249,
CC PubMed:16495336, PubMed:17709393, PubMed:18617507, PubMed:18286207,
CC PubMed:20679487). Isoform 1 modulates the stress response to hypoxia
CC and cytokines, such as interleukin-1 beta (IL1B) and this is dependent
CC on its interaction with MAPK8IP1, which assembles mitogen-activated
CC protein kinase (MAPK) complexes (PubMed:17709393). Inhibition of signal
CC transmission mediated by the assembly of MAPK8IP1-MAPK complexes
CC reduces JNK phosphorylation and JUN-dependent transcription
CC (PubMed:18286207). Phosphorylates 'Thr-18' of p53/TP53, histone H3, and
CC may also phosphorylate MAPK8IP1 (PubMed:16704422). Phosphorylates BANF1
CC and disrupts its ability to bind DNA and reduces its binding to LEM
CC domain-containing proteins (PubMed:16495336). Down-regulates the
CC transactivation of transcription induced by ERBB2, HRAS, BRAF, and MEK1
CC (PubMed:20679487). Blocks the phosphorylation of ERK in response to
CC ERBB2 and HRAS (PubMed:20679487). Can also phosphorylate the following
CC substrates that are commonly used to establish in vitro kinase
CC activity: casein, MBP and histone H2B, but it is not sure that this is
CC physiologically relevant (PubMed:14645249).
CC {ECO:0000269|PubMed:14645249, ECO:0000269|PubMed:16495336,
CC ECO:0000269|PubMed:16704422, ECO:0000269|PubMed:17709393,
CC ECO:0000269|PubMed:18286207, ECO:0000269|PubMed:18617507,
CC ECO:0000269|PubMed:20679487}.
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. {ECO:0000269|PubMed:16704422}.
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:16495336};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:17990;
CC Evidence={ECO:0000269|PubMed:16495336};
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:16495336,
CC ECO:0000269|PubMed:16704422};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:46609;
CC Evidence={ECO:0000269|PubMed:16495336, ECO:0000269|PubMed:16704422};
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 (PubMed:20679487, PubMed:17709393, PubMed:18286207). Isoform 1 and
CC isoform 2 interact with RAN and MAPK8IP1 (PubMed:18286207,
CC PubMed:18617507). {ECO:0000269|PubMed:17709393,
CC ECO:0000269|PubMed:18286207, ECO:0000269|PubMed:18617507,
CC 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 -!- SUBUNIT: (Microbial infection) Isoform 1 interacts with vaccinia
CC protein B12. {ECO:0000269|PubMed:31341052,
CC ECO:0000269|PubMed:33177193}.
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
CC {ECO:0000269|PubMed:16704422}. Endoplasmic reticulum membrane
CC {ECO:0000269|PubMed:16704422}; Single-pass type IV membrane protein
CC {ECO:0000255}. Mitochondrion membrane {ECO:0000269|PubMed:16704422};
CC Single-pass type IV membrane protein {ECO:0000255}. Nucleus envelope
CC {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 {ECO:0000303|PubMed:16704422};
CC IsoId=Q86Y07-1; Sequence=Displayed;
CC Name=2; Synonyms=VRK2B {ECO:0000303|PubMed:16704422};
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]: Autophosphorylated. {ECO:0000269|PubMed:14645249,
CC ECO:0000269|PubMed:16704422}.
CC -!- PTM: [Isoform 2]: Autophosphorylated. {ECO:0000269|PubMed:16704422}.
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";
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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 AlphaFoldDB; Q86Y07; -.
DR SMR; Q86Y07; -.
DR BioGRID; 113283; 244.
DR IntAct; Q86Y07; 56.
DR MINT; Q86Y07; -.
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; 218 antibodies from 30 providers.
DR DNASU; 7444; -.
DR Ensembl; ENST00000340157.9; ENSP00000342381.4; ENSG00000028116.18. [Q86Y07-1]
DR Ensembl; ENST00000412104.6; ENSP00000404156.3; ENSG00000028116.18. [Q86Y07-4]
DR Ensembl; ENST00000417641.6; ENSP00000402375.2; ENSG00000028116.18. [Q86Y07-5]
DR Ensembl; ENST00000435505.6; ENSP00000408002.2; ENSG00000028116.18. [Q86Y07-1]
DR Ensembl; ENST00000440705.6; ENSP00000398323.2; ENSG00000028116.18. [Q86Y07-3]
DR Ensembl; ENST00000648897.1; ENSP00000497378.1; ENSG00000028116.18. [Q86Y07-2]
DR GeneID; 7444; -.
DR KEGG; hsa:7444; -.
DR MANE-Select; ENST00000340157.9; ENSP00000342381.4; NM_006296.7; NP_006287.2.
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 MalaCards; VRK2; -.
DR MIM; 602169; gene.
DR neXtProt; NX_Q86Y07; -.
DR OpenTargets; ENSG00000028116; -.
DR PharmGKB; PA37331; -.
DR VEuPathDB; HostDB:ENSG00000028116; -.
DR eggNOG; KOG1164; Eukaryota.
DR GeneTree; ENSGT00940000158042; -.
DR HOGENOM; CLU_019279_4_3_1; -.
DR InParanoid; Q86Y07; -.
DR OMA; YCESQIL; -.
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 Reactome; R-HSA-9013149; RAC1 GTPase cycle.
DR Reactome; R-HSA-9013404; RAC2 GTPase cycle.
DR Reactome; R-HSA-9013405; RHOD GTPase cycle.
DR Reactome; R-HSA-9013408; RHOG GTPase cycle.
DR Reactome; R-HSA-9013423; RAC3 GTPase cycle.
DR SignaLink; Q86Y07; -.
DR SIGNOR; Q86Y07; -.
DR BioGRID-ORCS; 7444; 13 hits in 1118 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 monocyte and 199 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:RHEA.
DR GO; GO:0004674; F:protein serine/threonine kinase activity; IDA:UniProtKB.
DR GO; GO:0034599; P:cellular response to oxidative stress; IMP: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: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:0007165; P:signal transduction; IBA:GO_Central.
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 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 35..43
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 61
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
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:0007829|PDB:2V62"
FT STRAND 28..34
FT /evidence="ECO:0007829|PDB:2V62"
FT STRAND 43..51
FT /evidence="ECO:0007829|PDB:2V62"
FT HELIX 53..55
FT /evidence="ECO:0007829|PDB:2V62"
FT STRAND 58..64
FT /evidence="ECO:0007829|PDB:2V62"
FT STRAND 65..67
FT /evidence="ECO:0007829|PDB:5UU1"
FT HELIX 69..80
FT /evidence="ECO:0007829|PDB:2V62"
FT HELIX 83..93
FT /evidence="ECO:0007829|PDB:2V62"
FT STRAND 103..113
FT /evidence="ECO:0007829|PDB:2V62"
FT STRAND 115..122
FT /evidence="ECO:0007829|PDB:2V62"
FT STRAND 124..127
FT /evidence="ECO:0007829|PDB:2V62"
FT HELIX 128..131
FT /evidence="ECO:0007829|PDB:2V62"
FT HELIX 134..136
FT /evidence="ECO:0007829|PDB:2V62"
FT HELIX 140..159
FT /evidence="ECO:0007829|PDB:2V62"
FT HELIX 169..171
FT /evidence="ECO:0007829|PDB:2V62"
FT STRAND 172..178
FT /evidence="ECO:0007829|PDB:2V62"
FT STRAND 181..184
FT /evidence="ECO:0007829|PDB:2V62"
FT HELIX 187..189
FT /evidence="ECO:0007829|PDB:6NCG"
FT STRAND 191..194
FT /evidence="ECO:0007829|PDB:2V62"
FT HELIX 195..197
FT /evidence="ECO:0007829|PDB:2V62"
FT HELIX 206..208
FT /evidence="ECO:0007829|PDB:2V62"
FT TURN 214..216
FT /evidence="ECO:0007829|PDB:2V62"
FT HELIX 219..223
FT /evidence="ECO:0007829|PDB:2V62"
FT HELIX 229..245
FT /evidence="ECO:0007829|PDB:2V62"
FT HELIX 251..253
FT /evidence="ECO:0007829|PDB:2V62"
FT HELIX 257..269
FT /evidence="ECO:0007829|PDB:2V62"
FT TURN 270..272
FT /evidence="ECO:0007829|PDB:2V62"
FT HELIX 273..278
FT /evidence="ECO:0007829|PDB:2V62"
FT HELIX 286..296
FT /evidence="ECO:0007829|PDB:2V62"
FT HELIX 306..313
FT /evidence="ECO:0007829|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
