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Catalytic domain of the Serine/Threonine protein kinase, Vaccinia Related Kinase 2 STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. VRKs were initially discovered due to its similarity to vaccinia virus B1R STK, which is important for viral replication. They play important roles in cell signaling, nuclear envelope dynamics, apoptosis, and stress responses. Vertebrates contain three VRK proteins. VRK2 exists as two alternative splice forms, A and B, which differ in their C-terminal regions. VRK2A, the predominant isoform, contains a hydrophobic tail and is anchored to the ER and mitochondria. It is expressed in all cell types. VRK2B lacks a membrane-anchor tail and is detected in the cytosol and the nucleus. Like VRK1, it can stabilize p53. VRK2B functionally replaces VRK1 in the nucleus of cell types where VRK1 is absent. VRK2 modulates hypoxia-induced stress responses by interacting with TAK1, an atypical MAPK kinase kinase which triggers cascades that activate JNK following oxidative stress. VRK2 also interacts with JIP1, a scaffold protein that assembles three consecutive members of a MAPK pathway. This interaction prevents the association of JNK with the signaling complex, leading to reduced phosphorylation and AP1-dependent transcription. The VRK2 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. |
Jiyao W et al.(2023). "The conserved domain database in 2023.",