VRK1 (Vaccinia-related kinase 1)

	VRK1 gene structure based on data available in the Ensembl release 43. Upstream non-coding exons (green). Coding exons (yellow), 3' unstranslated sequence (red). The size of the exons in nucleotides is indicated below each exon. Exon number is indicated within the exon.
Description	13 exons in 84.22 kilobases. Transcription initiated from cetromere to telomere direction.
Transcription	Initiation codon located in exon 2. Normal message is 1702 nucleotides. Some alternatively spliced RNA messages have been detected; but they are likely to represent splicing intermediates since there is no protein has been detected expressed from these alternative messages in humans.
Pseudogene	None. There are two closely related genes VRK2 and VRK3. SNP: 289 single nucleotide polymorphisms identified in human VRK1. ALLELE VARIANTS: CA Polymorphisms. Near the PAPOLA (Polyadenyl polymerase) with respect to VRK1 there is a polymorphic dinucleotide (CA) sequence that has high heterozygosity (0.81). Might be a useful marker in the genetic study of disorders localized at the 14q32 region, such as autosomal recessive congenital microphthalmia (CMIC).

Note	Enzyme Number (IUBMB): "EC 2.7.11.1".
	ABRS: ATP-binding region signature SRPKAS: Ser/Thr protein kinases active-site signature ELTS:Endosomal-lysosomal targeting sequence NLS: Nuclear localization signal
Description	Protein of 396 aminoacids. 46 kDa. Serine-threonine kinase domain (residues 26-300). Nuclear localization signal (in C-terminal region) Protein autophosphorylated in several residues.
Expression	VRK1 is widely expressed in proliferating cells, normal and tumoral. It is not present in quiescent or differentiated cells that do not divide in human biopsies.
Localisation	Subcellular localisation varies depending on cell type and growth conditions. Most commonly VRK1 is expressed and detected in the nucleus, excluding the nucleolus. However, in some cells it is in the cytosol, particularly associated with endoplasmic reticulum and Golgi. Occasionally it is observed in the nucleolus, but outside the nucleus .The regulation of the subcellular localization is unknown.
Function	Serine-threonine kinase activity. Phosphorylates p53 in Threonine-18 preventing its interaction with Hdm2 and activates p53-dependent transcription. Phosphorylates c-Jun and ATF2 transcription factors. VRK1 also phosphorylates BAF1 required for nuclear envelope assembly. In human cell lines siRNA specific for VRK1 results in defective cell proliferation. The level of VRK1 protein is regulated proteolytically by a p53-dependent-transcription mechanism. This mechanism results in the induction of a targeting of VRK1 to enter the endosomal-lysosomal pathway.
Homology	The kinase domain is highly homologous to that in other ser-thr kinases. The C-terminal region has no homology to any known protein or domain. This C-terminal region of VRK1 is different form that in human VRK2, or in the VRK-1 homolog of distant species such as Drosophila, C. elegans or Dario Rerio. This C-terminal divergence suggest the possibility of different protein interactions and thus of differential regulation.

	Localization of loss of heterozygosis (LOH) and translocation breakpoints reported in 14q32.2. The breakpoint cluster region has multiple DNAseI hypersensitive sites.

Search in all EBI   NCBI

For comments and suggestions or contributions, please contact us