Serine/threonine kinase that regulates several signal transduction pathways (PubMed:14645249). Modulates the stress response to hypoxia and cytokines, such as interleukin-1 beta (IL1B) and this is dependent on its interaction with MAPK8IP1, which assembles mitogen-activated protein kinase (MAPK) complexes (By similarity). Inhibition of signal transmission mediated by the assembly of MAPK8IP1-MAPK complexes reduces JNK phosphorylation and JUN-dependent transcription (By similarity). Phosphorylates histone H3 (By similarity). Phosphorylates 'Thr-18' of p53/TP53, and thereby increases its stability and activity (By similarity). Phosphorylates BANF1 and disrupts its ability to bind DNA and reduces its binding to LEM domain-containing proteins (By similarity). Down-regulates the transactivation of transcription induced by ERBB2, HRAS, BRAF, and MEK1 (By similarity). Blocks the phosphorylation of ERK in response to ERBB2 and HRAS (By similarity). May also phosphorylate MAPK8IP1 (By similarity). Can also phosphorylate the following substrates that are commonly used to establish in vitro kinase activity: casein, MBP and histone H2B, but it is not sure that this is physiologically relevant (By similarity). ATP + L-seryl-[protein] = ADP + H(+) + O-phospho-L-seryl-[protein] ATP + L-threonyl-[protein] = ADP + H(+) + O-phospho-L-threonyl-[protein] Interacts with MAP3K7, MAP2K7, MAP2K1, KSR1, RAN and MAPK8IP1. Expressed in liver, kidney and muscle. Weakly expressed in thymus, bone marrow and spleen. Weakly expressed in embryo compared to VRK1 and VRK3. Expressed from 10.5 dpc to 14 dpc in developing liver and then decreases. It increases again from 17.5 dpc and remains thereafter. Highly expressed in hematopoietic embryonic tissues from 10.5 dpc to 14.5 dpc. Weakly expressed in the yolk-sac. Autophosphorylated. Belongs to the protein kinase superfamily. CK1 Ser/Thr protein kinase family. VRK subfamily.