VRK2

Summary

Gene Symbol: VRK2
Description: vaccinia related kinase 2
Alias: serine/threonine-protein kinase VRK2, vaccinia virus B1R-related kinase 2
Species: human
Products:     VRK2

Top Publications

  1. Nichols R, Wiebe M, Traktman P. The vaccinia-related kinases phosphorylate the N' terminus of BAF, regulating its interaction with DNA and its retention in the nucleus. Mol Biol Cell. 2006;17:2451-64 pubmed
    ..Herein, we demonstrate that B1, VRK1, and VRK2 efficiently phosphorylate the extreme N' terminus of the BAF protein (Barrier to Autointegration Factor)...
  2. Vázquez Cedeira M, Lazo P. Human VRK2 (vaccinia-related kinase 2) modulates tumor cell invasion by hyperactivation of NFAT1 and expression of cyclooxygenase-2. J Biol Chem. 2012;287:42739-50 pubmed publisher
    Human VRK2 (vaccinia-related kinase 2), a kinase that emerged late in evolution, affects different signaling pathways, and some carcinomas express high levels of VRK2...
  3. Blanco S, Sanz Garcia M, Santos C, Lazo P. Modulation of interleukin-1 transcriptional response by the interaction between VRK2 and the JIP1 scaffold protein. PLoS ONE. 2008;3:e1660 pubmed publisher
    ..Protein interactions are likely to modulate these pathways. Vaccinia-related kinase-2 (VRK2) is a novel human kinase that can modulate different signaling pathways...
  4. Sanz Garcia M, López Sánchez I, Lazo P. Proteomics identification of nuclear Ran GTPase as an inhibitor of human VRK1 and VRK2 (vaccinia-related kinase) activities. Mol Cell Proteomics. 2008;7:2199-214 pubmed publisher
    ..Ran is a novel negative regulator of nuclear VRK1 and VRK2 kinase activity, which may vary in different subcellular localizations generating an asymmetric intracellular ..
  5. Steinberg S, de Jong S, Andreassen O, Werge T, Børglum A, Mors O, et al. Common variants at VRK2 and TCF4 conferring risk of schizophrenia. Hum Mol Genet. 2011;20:4076-81 pubmed publisher
    ..novel variants showing genome-wide significant association: rs2312147[C], upstream of vaccinia-related kinase 2 (VRK2) [odds ratio (OR) = 1.09, P = 1...
  6. Scheeff E, Eswaran J, Bunkoczi G, Knapp S, Manning G. Structure of the pseudokinase VRK3 reveals a degraded catalytic site, a highly conserved kinase fold, and a putative regulatory binding site. Structure. 2009;17:128-38 pubmed publisher
    ..We present the first structure of a pseudokinase, VRK3, and that of its closest active relative, VRK2. Profound changes to the active site region underlie the loss of catalytic activity, and VRK3 cannot bind ATP ..
  7. Li M, Wang Y, Zheng X, Ikeda M, Iwata N, Luo X, et al. Meta-analysis and brain imaging data support the involvement of VRK2 (rs2312147) in schizophrenia susceptibility. Schizophr Res. 2012;142:200-5 pubmed publisher
    ..Here we analyzed 5 genome-wide supported variants in a Han Chinese sample, and the variant rs2312147 at VRK2 showed significant association, which was confirmed in the meta-analysis combining multiple Asian and European ..
  8. Steffens M, Leu C, Ruppert A, Zara F, Striano P, Robbiano A, et al. Genome-wide association analysis of genetic generalized epilepsies implicates susceptibility loci at 1q43, 2p16.1, 2q22.3 and 17q21.32. Hum Mol Genet. 2012;21:5359-72 pubmed publisher
    ..The associated regions harbor high-ranking candidate genes: CHRM3 at 1q43, VRK2 at 2p16.1, ZEB2 at 2q22.3, SCN1A at 2q24.3 and PNPO at 17q21.32...
  9. Fernández I, Pérez Rivas L, Blanco S, Castillo Dominguez A, Lozano J, Lazo P. VRK2 anchors KSR1-MEK1 to endoplasmic reticulum forming a macromolecular complex that compartmentalizes MAPK signaling. Cell Mol Life Sci. 2012;69:3881-93 pubmed publisher

More Information

Publications46

  1. Sanz Garcia M, Vázquez Cedeira M, Kellerman E, Renbaum P, Levy Lahad E, Lazo P. Substrate profiling of human vaccinia-related kinases identifies coilin, a Cajal body nuclear protein, as a phosphorylation target with neurological implications. J Proteomics. 2011;75:548-60 pubmed publisher
    ..In this report the substrate specificity of atypical human vaccinia-related kinases (VRK1 and VRK2) using a human peptide-array containing 1080 sequences phosphorylated in known signaling pathways has been studied...
  2. Vázquez Cedeira M, Barcia Sanjurjo I, Sanz Garcia M, Barcia R, Lazo P. Differential inhibitor sensitivity between human kinases VRK1 and VRK2. PLoS ONE. 2011;6:e23235 pubmed publisher
    Human vaccinia-related kinases (VRK1 and VRK2) are atypical active Ser-Thr kinases implicated in control of cell cycle entry, apoptosis and autophagy, and affect signalling by mitogen activated protein kinases (MAPK)...
  3. Fernández I, Blanco S, Lozano J, Lazo P. VRK2 inhibits mitogen-activated protein kinase signaling and inversely correlates with ErbB2 in human breast cancer. Mol Cell Biol. 2010;30:4687-97 pubmed publisher
    ..In this work, we study the effect of VRK2 on MAPK signaling using breast cancer as a model...
  4. Stefansson H, Ophoff R, Steinberg S, Andreassen O, Cichon S, Rujescu D, et al. Common variants conferring risk of schizophrenia. Nature. 2009;460:744-7 pubmed publisher
    ..2. Our findings implicating the MHC region are consistent with an immune component to schizophrenia risk, whereas the association with NRGN and TCF4 points to perturbation of pathways involved in brain development, memory and cognition. ..
  5. Nezu J, Oku A, Jones M, Shimane M. Identification of two novel human putative serine/threonine kinases, VRK1 and VRK2, with structural similarity to vaccinia virus B1R kinase. Genomics. 1997;45:327-31 pubmed
    ..7% identity over 300 amino acids). This gene has been named VRK2. Comparison of VRK1 with VRK2 indicates that they encode structurally related putative Ser/Thr protein kinases...
  6. Blanco S, Santos C, Lazo P. Vaccinia-related kinase 2 modulates the stress response to hypoxia mediated by TAK1. Mol Cell Biol. 2007;27:7273-83 pubmed
    ..This activation of TAK1-JIP1-JNK is suppressed by vaccinia-related kinase 2 (VRK2). VRK2A is able to interact with TAK1 by its C-terminal region, forming stable complexes...
  7. Li L, Liu M, Shih H, Tsai C, Chen J. Human cellular protein VRK2 interacts specifically with Epstein-Barr virus BHRF1, a homologue of Bcl-2, and enhances cell survival. J Gen Virol. 2006;87:2869-78 pubmed publisher
    ..by the yeast two-hybrid system and a cellular gene encoding human vaccinia virus B1R kinase-related kinase 2 (VRK2) was isolated...
  8. Blanco S, Klimcakova L, Vega F, Lazo P. The subcellular localization of vaccinia-related kinase-2 (VRK2) isoforms determines their different effect on p53 stability in tumour cell lines. FEBS J. 2006;273:2487-504 pubmed
    VRK is a new kinase family of unknown function. Endogenous human vacinia-related kinase 2 (VRK2) protein is present in both the nucleus and the cytosol, which is a consequence of alternative splicing of two VRK2 messages coding for ..
  9. Nichols R, Traktman P. Characterization of three paralogous members of the Mammalian vaccinia related kinase family. J Biol Chem. 2004;279:7934-46 pubmed
    ..and Traktman, P. (2004) J. Virol. 78, 1992-2005). This mammalian kinase family comprises three members, VRK1, VRK2, and VRK3...
  10. Dashti H, Jones S, Wood A, Lane J, van Hees V, Wang H, et al. Genome-wide association study identifies genetic loci for self-reported habitual sleep duration supported by accelerometer-derived estimates. Nat Commun. 2019;10:1100 pubmed publisher
    ..Replication is observed for PAX8, VRK2, and FBXL12/UBL5/PIN1 loci in the CHARGE study (n = 47,180; p < 6...
  11. Qu X, Li H, Braziel R, Passerini V, Rimsza L, Hsi E, et al. Genomic alterations important for the prognosis in patients with follicular lymphoma treated on SWOG study S0016. Blood. 2018;: pubmed publisher
    ..007, OR=2.55 (1.29, 5.03)] and 2p cnLOH [P=0.005, OR=10.9 (2.08, 57.2)], 2p gain specifically encompassing VRK2 and FANCL predicted PFS [P=0.01, HR=1.80 (1.14, 2.68)] as well as OS [P=0.005, 2.40 (1.30, 4...
  12. Hirata N, Suizu F, Matsuda Lennikov M, Tanaka T, Edamura T, Ishigaki S, et al. Functional characterization of lysosomal interaction of Akt with VRK2. Oncogene. 2018;37:5367-5386 pubmed publisher
    ..b>VRK2 interacts with Akt1 and Akt2, but not with Akt3; the C terminus of Akt and the N terminus of VRK2 facilitate the ..
  13. Liu J, Tong L, Song S, Niu Y, Li J, Wu X, et al. Novel and de novo mutations in pediatric refractory epilepsy. Mol Brain. 2018;11:48 pubmed publisher
    ..mutations detected in unclassified epilepsy patients involve the SCN8A, CACNA1A, GABRB3, GABRA1, IQSEC2, TSC1, VRK2, ATP1A2, PCDH19, SLC9A6 and CHD2 genes...
  14. Chen C, Chern S, Wu P, Chen S, Lai S, Chuang T, et al. Prenatal diagnosis of a 3.2-Mb 2p16.1-p15 duplication associated with familial intellectual disability. Taiwan J Obstet Gynecol. 2018;57:578-582 pubmed publisher
    ..0 [GRCh37 (hg19)] encompassing eight Online Mendelian Inheritance in Man (OMIM) genes of VRK2, FANCL, BCL11A, PAPOLG, REL, PUS10, PEX13 and USP34 in the fetus and the two women...
  15. Liep J, Kilic E, Meyer H, Busch J, Jung K, Rabien A. Cooperative Effect of miR-141-3p and miR-145-5p in the Regulation of Targets in Clear Cell Renal Cell Carcinoma. PLoS ONE. 2016;11:e0157801 pubmed publisher
    ..Both miRNAs were recognized as post-transcriptional regulators of the targets EAPP, HS6ST2, LOX, TGFB2 and VRK2. Additionally, they showed a cooperative effect again as demonstrated by a significantly increased inhibition of ..
  16. Xiao X, Luo X, Chang H, Liu Z, Li M. Evaluation of European Schizophrenia GWAS Loci in Asian Populations via Comprehensive Meta-Analyses. Mol Neurobiol. 2017;54:4071-4080 pubmed publisher
    ..Among the 19 GWAS loci, we replicated the risk associations of nine markers (e.g., SNPs at VRK2, ITIH3/4, NDST3, NOTCH4) surpassing significance level (two-tailed P?<?0...
  17. Quiel A, Jürgen B, Greinacher A, Lassen S, Wörl R, Witt S, et al. Sensitive detection of idiotypic platelet-reactive alloantibodies by an electrical protein chip. Biosens Bioelectron. 2012;36:207-11 pubmed publisher
    ..With this electrical chip assay it is possible to detect antibodies against HPA-1a, HPA-5b and HLA with high sensitivity and specificity in less than half the duration of the MAIPA protocol with similar intra- and interassay variance. ..
  18. Yue W, Yu X, Zhang D. Progress in genome-wide association studies of schizophrenia in Han Chinese populations. NPJ Schizophr. 2017;3:24 pubmed publisher
    ..histocompatibility complex, microRNA 137 (MIR137), zinc finger protein 804A (ZNF804A), vaccinia related kinase 2 (VRK2), and arsenite methyltransferase (AS3MT), across both European and East Asian populations...
  19. Tesli M, Wirgenes K, Hughes T, Bettella F, Athanasiu L, Hoseth E, et al. VRK2 gene expression in schizophrenia, bipolar disorder and healthy controls. Br J Psychiatry. 2016;209:114-20 pubmed publisher
    Common variants in the Vaccinia-related kinase 2 (VRK2) gene have been associated with schizophrenia, but the relevance of its encoded protein VRK2 in the disorder remains unclear...
  20. Sohn H, Kim B, Kim K, Kim M, Choi T, Lee S. Effects of VRK2 (rs2312147) on white matter connectivity in patients with schizophrenia. PLoS ONE. 2014;9:e103519 pubmed publisher
    ..association studies of schizophrenia reported a novel risk variant, rs2312147 at vaccinia-related kinase 2 gene (VRK2), in multiple Asian and European samples...
  21. Kudoh A, Takahama S, Sawasaki T, Ode H, Yokoyama M, Okayama A, et al. The phosphorylation of HIV-1 Gag by atypical protein kinase C facilitates viral infectivity by promoting Vpr incorporation into virions. Retrovirology. 2014;11:9 pubmed publisher
    ..Furthermore, aPKC inhibition efficiently suppresses HIV-1 infectivity in macrophages. aPKC may therefore be an intriguing therapeutic target for HIV-1 infection. ..
  22. Barcia Sanjurjo I, Vázquez Cedeira M, Barcia R, Lazo P. Sensitivity of the kinase activity of human vaccinia-related kinase proteins to toxic metals. J Biol Inorg Chem. 2013;18:473-82 pubmed publisher
    The human vaccinia-related kinase (VRK) proteins VRK1 and VRK2 regulate different processes, such as the cell cycle, DNA damage response, and signaling by mitogen-activated protein kinases in response to growth factors or cellular stress...
  23. Fu T, Ren H, Zhang J, Ren P, Enyedy I, Li G. Role of bivalent cations in structural stabilities of new drug targets--vaccinia-related kinases (VRK) from molecular dynamics simulations. Curr Pharm Des. 2013;19:2269-81 pubmed
    ..which was the first solved crystal structure of the pseudokinase, and that of its closest active relatives VRK1 and VRK2. Toward this end, a series of molecular dynamics simulations have been performed with different divalent cations ..
  24. Azimi T, Ghafouri Fard S, Davood Omrani M, Mazdeh M, Arsang Jang S, Sayad A, et al. Vaccinia Related Kinase 2 (VRK2) expression in neurological disorders: schizophrenia, epilepsy and multiple sclerosis. Mult Scler Relat Disord. 2018;19:15-19 pubmed publisher
    ..The Vaccinia-Related Kinase 2 (VRK2) gene codes for a serine threonine kinase recently reported to be contributed in the pathogenesis of some ..
  25. Valbuena A, Blanco S, Vega F, Lazo P. The C/H3 domain of p300 is required to protect VRK1 and VRK2 from their downregulation induced by p53. PLoS ONE. 2008;3:e2649 pubmed publisher
    ..A similar downregulatory effect can also be detected with VRK2 protein...
  26. Couñago R, Allerston C, Savitsky P, Azevedo H, Godoi P, Wells C, et al. Structural characterization of human Vaccinia-Related Kinases (VRK) bound to small-molecule inhibitors identifies different P-loop conformations. Sci Rep. 2017;7:7501 pubmed publisher
    The human genome encodes two active Vaccinia-related protein kinases (VRK), VRK1 and VRK2. These proteins have been implicated in a number of cellular processes and linked to a variety of tumors...
  27. Birendra Kc -, May D, Benson B, Kim D, Shivega W, Ali M, et al. VRK2A is an A-type lamin-dependent nuclear envelope kinase that phosphorylates BAF. Mol Biol Cell. 2017;28:2241-2250 pubmed publisher
    ..These studies identify vaccinia-related kinase-2 (VRK2) as a candidate constituent of the INM...
  28. Olson A, Rico A, Wang Z, Delhon G, Wiebe M. Deletion of the Vaccinia Virus B1 Kinase Reveals Essential Functions of This Enzyme Complemented Partly by the Homologous Cellular Kinase VRK2. J Virol. 2017;91: pubmed publisher
    ..Using cell lines devoid of either VRK1 or VRK2, we tested this hypothesis and discovered that VRK2 expression facilitates DNA replication and allows later stages ..
  29. Yu H, Yan H, Li J, Li Z, Zhang X, Ma Y, et al. Common variants on 2p16.1, 6p22.1 and 10q24.32 are associated with schizophrenia in Han Chinese population. Mol Psychiatry. 2017;22:954-960 pubmed publisher
    ..1 (rs1051061, in an exon of VRK2, P=1.14 × 10-12, odds ratio (OR)=1.17), 6p22.1 (rs115070292 in an intron of GABBR1, P=4...
  30. Jones S, Tyrrell J, Wood A, Beaumont R, Ruth K, Tuke M, et al. Genome-Wide Association Analyses in 128,266 Individuals Identifies New Morningness and Sleep Duration Loci. PLoS Genet. 2016;12:e1006125 pubmed publisher
    ..6 minutes per allele, 95% CI [1.9, 3.2], P = 5.7x10-16) and identified and replicated two novel associations at VRK2 (2.0 minutes per allele, 95% CI [1.3, 2.7], P = 1.2x10-9; and 1.6 minutes per allele, 95% CI [1.1, 2.2], P = 7...
  31. del Puerto Nevado L, Marin Arango J, Fernandez Aceñero M, Arroyo Manzano D, Martinez Useros J, Borrero Palacios A, et al. Predictive value of vrk 1 and 2 for rectal adenocarcinoma response to neoadjuvant chemoradiation therapy: a retrospective observational cohort study. BMC Cancer. 2016;16:519 pubmed publisher
    ..We evaluated the kinases VRK1 and VRK2, which are known to play multiple roles in cellular proliferation, cell cycle regulation, and carcinogenesis, and ..
  32. Chang H, Zhang C, Xiao X, Pu X, Liu Z, Wu L, et al. Further evidence of VRK2 rs2312147 associated with schizophrenia. World J Biol Psychiatry. 2016;17:457-66 pubmed publisher
    Previous genome-wide association studies (GWAS) have reported that rs2312147 near the VRK2 gene was significantly associated with schizophrenia in populations of European descent, but negative results have also been observed...
  33. Zhang B, Gao C, Zhang H, Yang B, Yin J, Wei S, et al. Association of the VRK2 gene rs3732136 polymorphism with schizophrenia in a Northwest Chinese Han population. Genet Mol Res. 2015;14:9404-11 pubmed publisher
    Previous studies have found that the vaccinia related kinase 2 gene (VRK2) polymorphism was associated with schizophrenia (SCZ) in the worldwide population...
  34. Kim S, Lee D, Lee J, Song H, Kim H, Kim K. Vaccinia-Related Kinase 2 Controls the Stability of the Eukaryotic Chaperonin TRiC/CCT by Inhibiting the Deubiquitinating Enzyme USP25. Mol Cell Biol. 2015;35:1754-62 pubmed publisher
    ..We have previously shown that vaccinia-related kinase 2 (VRK2) downregulates TRiC protein levels through the ubiquitin-proteasome system by recruiting the E3 ligase COP1...
  35. . Genetic determinants of common epilepsies: a meta-analysis of genome-wide association studies. Lancet Neurol. 2014;13:893-903 pubmed publisher
    ..1 (p=9·99?×?10(-9)), implicating VRK2 or FANCL. No single nucleotide polymorphism achieved genome-wide significance for focal epilepsy...
  36. Kim S, Park D, Lee D, Kim W, Jeong Y, Lee J, et al. Vaccinia-related kinase 2 mediates accumulation of polyglutamine aggregates via negative regulation of the chaperonin TRiC. Mol Cell Biol. 2014;34:643-52 pubmed publisher
    ..Here, we propose that vaccinia-related kinase 2 (VRK2) is a critical enzyme that negatively regulates TRiC...
  37. Monsalve D, Merced T, Fernández I, Blanco S, Vázquez Cedeira M, Lazo P. Human VRK2 modulates apoptosis by interaction with Bcl-xL and regulation of BAX gene expression. Cell Death Dis. 2013;4:e513 pubmed publisher
    b>VRK2 is a novel Ser-Thr kinase whose VRK2A isoform is located in the endoplasmic reticulum and mitochondrial membranes. We have studied the potential role that VRK2A has in the regulation of mitochondrial-mediated apoptosis...