serine/threonine protein kinase VRK2; vaccinia-related kinase 2 (VRK2)

Function

• serine/threonine protein kinase
• regulates several signal transduction pathways
• isoform 1
  • modulates the stress response to hypoxia & cytokines, such as interleukin-1 beta (IL1B)
    • this is dependent on its interaction with MAPK8IP1, which assembles mitogen-activated protein kinase (MAPK) complexes
    • inhibition of signal transmission mediated by assembly of MAPK8IP1-MAPK complexes, reduces JNK phosphorylation & AP1-dependent transcription
  • VRK2 phosphorylates Thr-18 of p53/TP53, casein, MBP, histone H2B, histone H3 & MAPK8IP1
  • phosphorylates BANF1 & disrupts its ability to bind DNA & reduces its binding to LEM domain-containing proteins
  • downregulates transactivation of transcription induced by ERBB2, HRAS, BRAF, & MEK1
  • blocks phosphorylation of ERK in response to ERBB2 & HRAS
• isoform 2
  • phosphorylates Thr-18 of p53/TP53, casein, MBP, histone H2B, histone H3 & MAPK8IP
  • stabilizes p53/TP53 & activates its transcriptional activity
  • reduces p53/TP53 ubiquitination by MDM2 & promotes its acetylation by EP300
• RAN inhibits its autophosphorylation & its ability to phosphorylate histone H3
• isoform 1 & isoform 2 are autophosphorylated
• isoform 1 interacts with MAP3K7, MAP2K7, MAP2K1 & KSR1
• isoform 1 & isoform 2 interact with RAN & MAPK8IP1. isoform 1

Structure

• belongs to the protein kinase superfamily, CK1 Ser/Thr protein kinase family, VRK subfamily
• contains 1 protein kinase domain

Compartment

• isoform 1
  • cytoplasm
  • endoplasmic reticulum membrane
  • mitochondrial membrane
  • single-pass type 4 membrane protein
• isoform 2: cytoplasm., nucleus

Alternative splicing

named isoforms=5

Expression

• widely expressed
• highly expressed in fetal liver, skeletal muscle, pancreas, heart, peripheral blood leukocytes & testis
• isoform 1 & isoform 2 are expressed in various tumor cell lines
• expression of isoform 1 inversely correlates with ERBB2 in breast carcinomas (at protein level)

Pathology

• interacts with Epstein-Barr virus BHRF1; this interaction is involved in protecting cells from apoptosis

More general terms

• serine/threonine protein kinase VRK (Vaccinia-related kinase)
• membrane protein

Additional terms

• vaccinia virus

Database

• Entrez gene: http://www.ncbi.nlm.nih.gov/sites/entrez?db=gene&cmd=Retrieve&dopt=Graphics&list_uids=7444
• Kegg: http://www.genome.jp/dbget-bin/www_bget?hsa:7444
• OMIM: https://mirror.omim.org/entry/602169
• UniProt: http://www.uniprot.org/uniprot/Q86Y07.html