VRK

VRK stands for vaccinia-related kinase, a small family of serine/threonine protein kinases originally identified as homologs of the vaccinia virus kinase. In humans, the family comprises two main members, VRK1 and VRK2, encoded by the VRK1 and VRK2 genes. VRK1 is primarily localized in the nucleus, whereas VRK2 exists as isoforms with distinct subcellular distributions (for example, VRK2A is mainly cytoplasmic and VRK2B is predominantly nuclear). Both proteins share a conserved catalytic kinase domain and regulatory regions that influence substrate recognition and localization.

Functions of VRK proteins are centered on regulation of cell proliferation, chromatin dynamics, and the DNA damage response. Substrates attributed to VRKs include barrier-to-autointegration factor (BAF), histone H3, and transcription factors such as CREB and p53. Phosphorylation of BAF by VRK1 is linked to nuclear envelope reassembly after mitosis, while phosphorylation of p53 by VRK1 is implicated in modulating p53-dependent transcription and cell cycle control following genomic stress. Through histone and transcription factor phosphorylation, VRKs participate in chromatin organization and gene expression regulation. VRK1 and VRK2 also interact with signaling networks that influence cell survival and proliferation.

Regulation and expression patterns vary by tissue and developmental context. VRK1 is commonly associated with proliferative states and nuclear functions, while VRK2 isoforms contribute to both cytoplasmic and nuclear processes. The activity of VRKs is modulated by cellular localization, interaction with substrates, and upstream signals.

Clinical relevance and research: Altered VRK expression or activity has been linked to cancer and neurodevelopmental disorders. Rare VRK1 mutations have been associated with brain development anomalies such as microcephaly. Due to their roles in cell cycle control and DNA damage responses, VRKs are active areas of study for understanding chromatin dynamics and as potential targets in cancer biology.