Serine/threonine kinase that regulates several signal transduction pathways (PubMed:16704422, PubMed:14645249, PubMed:16495336, PubMed:17709393, PubMed:18617507, PubMed:18286207, PubMed:20679487). Isoform 1 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 (PubMed:17709393). Inhibition of signal transmission mediated by the assembly of MAPK8IP1-MAPK complexes reduces JNK phosphorylation and JUN-dependent transcription (PubMed:18286207). Phosphorylates 'Thr-18' of p53/TP53, histone H3, and may also phosphorylate MAPK8IP1 (PubMed:16704422). Phosphorylates BANF1 and disrupts its ability to bind DNA and reduces its binding to LEM domain-containing proteins (PubMed:16495336). Down-regulates the transactivation of transcription induced by ERBB2, HRAS, BRAF, and MEK1 (PubMed:20679487). Blocks the phosphorylation of ERK in response to ERBB2 and HRAS (PubMed:20679487). 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 (PubMed:14645249). Phosphorylates 'Thr-18' of p53/TP53, as well as histone H3. Reduces p53/TP53 ubiquitination by MDM2, promotes p53/TP53 acetylation by EP300 and thereby increases p53/TP53 stability and activity. ATP + L-seryl-[protein] = ADP + H(+) + O-phospho-L-seryl-[protein] ATP + L-threonyl-[protein] = ADP + H(+) + O-phospho-L-threonyl-[protein] RAN inhibits its autophosphorylation and its ability to phosphorylate histone H3. Isoform 1 interacts with MAP3K7, MAP2K7, MAP2K1 and KSR1 (PubMed:20679487, PubMed:17709393, PubMed:18286207). Isoform 1 and isoform 2 interact with RAN and MAPK8IP1 (PubMed:18286207, PubMed:18617507). (Microbial infection) Isoform 1 interacts with Epstein-Barr virus BHRF1; this interaction is involved in protecting cells from apoptosis. (Microbial infection) Isoform 1 interacts with vaccinia protein B12. Isoform 1 and isoform 2 are expressed in various tumor cell lines. Expression of isoform 1 inversely correlates with ERBB2 in breast carcinomas (at protein level). Widely expressed. Highly expressed in fetal liver, skeletal muscle, pancreas, heart, peripheral blood leukocytes and testis. Autophosphorylated. Autophosphorylated. Belongs to the protein kinase superfamily. CK1 Ser/Thr protein kinase family. VRK subfamily. Aberrant splicing.