Mammalian VRK (vaccinia-related kinases) were originally identified as two human EST, VRK1 and VRK2, expressed in proliferating cell lines and regenerating liver. These EST have homology to the catalytic region of the B1R kinase of vaccinia virus (Nezu et al. 1997) that is expressed early in viral infection and is required for viral DNA replication. These VRK proteins were classified as a new group of Ser-Thr kinases in the human kinome diverging very early from the same branch that led to casein kinase I (CK1) (Manning et al. 2002). This family has only one ortholog gene in invertebrates, such as C. elegans and Drosophila melanogaster, and is not present in yeast (Klerkx et al. 2009).
VRK2 Gene and Expression
The human VRK2gene is located in chromosome 2p16.1 and generates two messages by alternative splicing. Their translation generates two protein isoforms, VRK2A (also known as...
- Epilepsies. ILAECoC. Genetic determinants of common epilepsies: a meta-analysis of genome-wide association studies. Lancet Neurol. 2014;13:893–903. https://doi.org/10.1016/S1474-4422(14)70171-1.
- Irish Schizophrenia Genomics Consortium, the Wellcome Trust Case Control Consortium. Genome-wide association study implicates HLA-C*01:02 as a risk factor at the major histocompatibility complex locus in schizophrenia. Biol Psychiatry. 2012; https://doi.org/10.1016/j.biopsych.2012.05.035.CrossRefGoogle Scholar
- Rodriguez-Hernandez I, Vazquez-Cedeira M, Santos-Briz A, Garcia JL, Fernandez IF, Gomez-Moreta JA, et al. VRK2 identifies a subgroup of primary high-grade astrocytomas with a better prognosis. BMC Clin Pathol. 2013;13:23. https://doi.org/10.1186/1472-6890-13-23.CrossRefPubMedPubMedCentralGoogle Scholar
- Sanz-Garcia M, Vazquez-Cedeira M, Kellerman E, Renbaum P, Levy-Lahad E, Lazo PA. Substrate profiling of human vaccinia-related kinases identifies coilin, a Cajal body nuclear protein, as a phosphorylation target with neurological implications. J Proteome. 2011;75:548–60. https://doi.org/10.1016/j.jprot.2011.08.019.CrossRefGoogle Scholar
- Scheeff ED, 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. https://doi.org/10.1016/j.str.2008.10.018.CrossRefPubMedPubMedCentralGoogle Scholar