VRK2

This gene encodes a member of the vaccinia-related kinase (VRK) family of serine/threonine protein kinases. The encoded protein acts as an effector of signaling pathways that regulate apoptosis and tumor cell growth. Variants in this gene have been associated with schizophrenia. Alternative splicing results in multiple transcript variants that differ in their subcellular localization and biological activity. [provided by RefSeq, Jan 2014]

Full Name

Vaccinia Related Kinase 2

Function

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).
Isoform 2
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.

Biological Process

Biological Process cellular response to oxidative stress Source:UniProtKB1 Publication
Biological Process peptidyl-serine phosphorylation Source:GO_Central1 Publication
Biological Process protein autophosphorylation Source:UniProtKB2 Publications
Biological Process protein phosphorylation Source:ProtInc1 Publication
Biological Process regulation of interleukin-1-mediated signaling pathway Source:UniProtKB1 Publication
Biological Process regulation of MAPK cascade Source:UniProtKB1 Publication
Biological Process signal transduction Source:GO_Central1 Publication

Cellular Location

Isoform 1
Cytoplasm
Endoplasmic reticulum membrane
Mitochondrion membrane
Nucleus envelope
Isoform 2
Cytoplasm
Nucleus

Topology

Helical: 487-507

PTM

Isoform 1
Autophosphorylated.
Isoform 2
Autophosphorylated.