Recombinant Mouse Serine/threonine-protein kinase VRK1 (Vrk1)

Function

Serine/threonine kinase involved in the regulation of key cellular processes including the cell cycle, nuclear condensation, transcription regulation, and DNA damage response (PubMed:14645249, PubMed:33076429, PubMed:9521809). Controls chromatin organization and remodeling by mediating phosphorylation of histone H3 on 'Thr-4' and histone H2AX (H2aXT4ph) (By similarity). It also phosphorylates KAT5 in response to DNA damage, promoting KAT5 association with chromatin and histone acetyltransferase activity (PubMed:33076429). Is involved in the regulation of cell cycle progression of neural progenitors, and is required for proper cortical neuronal migration (PubMed:25609612). Is involved in neurite elongation and branching in motor neurons, and has an essential role in Cajal bodies assembly, acting through COIL phosphorylation and the control of coilin degradation (By similarity). Involved in Golgi disassembly during the cell cycle: following phosphorylation by PLK3 during mitosis, required to induce Golgi fragmentation (By similarity). Phosphorylates BANF1: disrupts its ability to bind DNA, reduces its binding to LEM domain-containing proteins and causes its relocalization from the nucleus to the cytoplasm (By similarity). Phosphorylates TP53BP1 and p53/TP53 on 'Thr-18', preventing the interaction between p53/TP53 and MDM2 (By similarity). Phosphorylates ATF2 which activates its transcriptional activity (By similarity). Phosphorylates JUN (By similarity)

Subcellular Location

Nucleus; Cytoplasm; Nucleus, Cajal body

Tissue Specificity

Highly expressed in testis. Expressed in liver, kidney and muscle. Weakly expressed in thymus, bone marrow and spleen

Subunit

Interacts with HDAC1, KAT2B, SETDB1, KDM3A and KDM4A (By similarity). Associates with the nucleosome through interactions with nucleosome DNA, histone H2A and histone H2B; the interaction with H2A and H2B is mediated by the nucleosome acidic patch, a cluster of negatively charged residues of H2A and H2B forming a cleft within the nucleosome core

• Zelko I.N. et al. Molecular cloning and characterization of a novel nuclear protein kinase in mice. — Arch. Biochem. Biophys. (1998)
• Carninci P. et al. The transcriptional landscape of the mammalian genome. — Science (2005)
• The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). — Genome Res. (2004)
• Vega F.M. et al. Expression of the VRK (vaccinia-related kinase) gene family of p53 regulators in murine hematopoietic development. — FEBS Lett. (2003)
• Nichols R.J. et al. Characterization of three paralogous members of the Mammalian vaccinia related kinase family. — J. Biol. Chem. (2004)
• Huttlin E.L. et al. A tissue-specific atlas of mouse protein phosphorylation and expression. — Cell (2010)
• Vinograd-Byk H. et al. The spinal muscular atrophy with pontocerebellar hypoplasia gene VRK1 regulates neuronal migration through an amyloid-beta precursor protein-dependent mechanism. — J. Neurosci. (2015)
• Martin-Doncel E. et al. VRK1 functional insufficiency due to alterations in protein stability or kinase activity of human VRK1 pathogenic variants implicated in neuromotor syndromes. — Sci. Rep. (2019)