VRK2: a widely expressed serine/threonine kinase of the CK1 group. A single-pass type IV membrane protein. Highly expressed in fetal liver, skeletal muscle, pancreas, heart, peripheral blood leukocytes and testis. Modulates the stress response to hypoxia mediated by TAK1. Interacts with JIP1, inhibiting mitogen-activated protein kinase (MAPK) signaling. Interacts with RAN, inhibiting its autophosphorylation. Five human isoforms produced by alternative splicing have been reported. Isoform 1 has a C-terminal hydrophobic region that that associates with the endoplasmic reticulum and mitochondria, colocalizing with calreticulin, calnexin, and mitochondrial markers. Its interaction with JIP1 modulates the stress response to hypoxia and cytokines such as IL1B. Inhibition of signal transmission mediated by the assembly of JIP1-MAPK complexes reduces JNK phosphorylation and JUN-dependent transcription. Phosphorylates p53 and BAF, inhibiting the latter's ability to bind DNA and reduces its binding to LEM domain-containing proteins. Downregulates the transactivation of transcription induced by HER2, HRAS, BRAF, and MEK1. Blocks the phosphorylation of ERK in response to HER2 and HRAS. Interacts with Epstein-Barr virus BHRF1, protecting cells from apoptosis. Interacts with TAK1, MKK7, MEK1, KSR, RAN and JIP1. Its expression in breast carcinomas inversely correlates with the expression of HER2. Isoform 2 is detected in both the cytoplasm and the nucleus. Phosphorylates p53, reducing its ubiquitination by MDM2 and promoting its acetylation by EP300, thereby increasing the stability and activity of p53.
Protein type: CK1 group; EC 2.7.11.1; Kinase, protein; Membrane protein, integral; Protein kinase, CK1; Protein kinase, Ser/Thr (non-receptor); VRK family
Chromosomal Location of Human Ortholog: 2p16.1
Cellular Component: cytoplasm; endoplasmic reticulum; endoplasmic reticulum membrane; mitochondrial membrane; nucleus; protein complex
Molecular Function: protein binding; protein domain specific binding; protein kinase binding; protein serine/threonine kinase activity
Biological Process: peptidyl-serine phosphorylation; protein amino acid autophosphorylation; protein amino acid phosphorylation; regulation of cell shape; regulation of MAPKKK cascade
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