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Beschreibung

Serine/threonine-protein kinase VRK1 (UniProt: Q99986, also known as EC: 2.7.11.1, Vaccinia-related kinase 1) is encoded by the VRK1 gene (Gene ID: 7443) in human. VRK1 is a serine/threonine kinase that is widely expressed with high expression in fetal liver, testis and thymus. Its protein kinase domain is located in the amino acids 37-317. VRK1 is involved in Golgi disassembly during the cell cycle and Golgi fragmentation. VRK1 phosphorylation by PLK3, which leads to induction of Golgi fragmentation. VRK1 acts by mediating phosphorylation of downstream target protein and is shown to phosphorylate threonine 18 of p53/TP53 and thereby prevent the interaction between p53/TP53 and MDM2. VRK1 is autophosphorylated at various serine and threonine residues, however, it does not impair its ability to phosphorylate p53/TP53. VRK1 is also shown to phosphorylate casein, histone H3, and ATF2, which activates its transcriptional activity. In cancer cell lines VRK1 is reported to phosphorylate histone H2A at threonine 120 that results in inappropriate gene expression, including up-regulation of cyclin D1, which can promote oncogenic transformations. Mutations in VRK1 gene have been linked to Pontocerebellar hypoplasia 1A, a condition characterized by an abnormally small cerebellum and brainstem, central and peripheral motor dysfunction from birth. (Ref.: Aihara, H., et al., (2016). Mol. Cell 64(1), 176-188).