background:
This gene encodes a member of the vaccinia-related kinase (VRK) family of serine/threonine protein kinases. This gene is widely expressed in human tissues and has increased expression in actively dividing cells, such as those in testis, thymus, fetal liver, and carcinomas. Its protein localizes to the nucleus and has been shown to promote the stability and nuclear accumulation of a transcriptionally active p53 molecule and, in vitro, to phosphorylate Thr18 of p53 and reduce p53 ubiquitination. This gene, therefore, may regulate cell proliferation. This protein also phosphorylates histone, casein, and the transcription factors ATF2 (activating transcription factor 2) and c-JUN.
Function:
Serine/threonine kinase involved in Golgi disassembly during the cell cycle: following phosphorylation by PLK3 during mitosis, required to induce Golgi fragmentation. Acts by mediating phosphorylation of downstream target protein. Phosphorylates 'Thr-18' of p53/TP53 and may thereby prevent the interaction between p53/TP53 and MDM2. Phosphorylates casein and histone H3. Phosphorylates BANF1: disrupts its ability to bind DNA, reduces its binding to LEM domain-containing proteins and causes its relocalization from the nucleus to the cytoplasm.
Subcellular Location:
Cytoplasm. Nucleus. Cytoplasm, cytoskeleton, spindle (By similarity). Note=Dispersed throughout the cell but not located on mitotic spindle or chromatids during mitosis.
Tissue Specificity:
Widely expressed. Highly expressed in fetal liver, testis and thymus.
Post-translational modifications:
Autophosphorylated at various serine and threonine residues. Autophosphorylation does not impair its ability to phosphorylate p53/TP53. Phosphorylation by PLK3 leads to induction of Golgi fragmentation during mitosis.
DISEASE:
Defects in VRK1 are the cause of pontocerebellar hypoplasia type 1A (PCH1A) [MIM:607596]; also called pontocerebellar hypoplasia with infantile spinal muscular atrophy or pontocerebellar hypoplasia with anterior horn cell disease. PCH1A is characterized by an abnormally small cerebellum and brainstem, central and peripheral motor dysfunction from birth, gliosis and anterior horn cell degeneration resembling infantile spinal muscular atrophy (SMA).
Similarity:
Belongs to the protein kinase superfamily. CK1 Ser/Thr protein kinase family. VRK subfamily.
Contains 1 protein kinase domain.
Database links:
UniProtKB/Swiss-Prot: Q99986.1
Important Note:
This product as supplied is intended for research use only, not for use in human, therapeutic or diagnostic applications.
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