Molecular Target Synopsis
Overview
Domains and Structures
Drugs and Clinical Candidates
Druggability
Chemistry
Ligand Efficiency Plot
Pathways
Family Cladogram
Interaction Network
Gene Expression
Gene Copy Number Variation
RNAi
Mutations
Germline Genetics

VRK2 (Q86Y07) - Overview - Molecular Target Synopsis

Protein


VRK2, Serine/threonine-protein kinase VRK2
Enzyme Classification 2.7.11.1
UniProt Q86Y07

Also Known as VRK2_HUMAN, VRK2

Serine/threonine kinase that regulates several signal transduction pathways. Isoform 1 modulates the stress response to hypoxia and cytokines, such as interleukin-1 beta (IL1B) and this is dependent on its interaction with MAPK8IP1, which assembles mitogen-activated protein kinase (MAPK) complexes. Inhibition of signal transmission mediated by the assembly of MAPK8IP1-MAPK complexes reduces JNK phosphorylation and JUN-dependent transcription. Phosphorylates 'Thr-18' of p53/TP53, histone H3, and may also phosphorylate MAPK8IP1. Phosphorylates BANF1 and disrupts its ability to bind DNA and reduces its binding to LEM domain-containing proteins. Downregulates the transactivation of transcription induced by ERBB2, HRAS, BRAF, and MEK1. Blocks the phosphorylation of ERK in response to ERBB2 and HRAS. Can also phosphorylate the following substrates that are commonly used to establish in vitro kinase activity: casein, MBP and histone H2B, but it is not sure that this is physiologically relevant., Isoform 2 phosphorylates 'Thr-18' of p53/TP53, as well as histone H3. Reduces p53/TP53 ubiquitination by MDM2, promotes p53/TP53 acetylation by EP300 and thereby increases p53/TP53 stability and activity. Isoform 1 interacts with MAP3K7, MAP2K7, MAP2K1 and KSR1. Isoform 1 and isoform 2 interact with RAN and MAPK8IP1.

6NCG
CRYSTAL STRUCTURE OF HUMAN VACCINIA-RELATED KINASE 2 (VRK-2) BOUND TO PYRIDIN-BENZENESULFONAMIDE INHIBITOR
RCSB/PDB
Inspect Structure
See all 3D Structures for VRK2

Isoforms / Transcripts (Protein Coding)


Sub-cellular localization


UniProt: VRK2 is active in the following subcellular-locations: cytoplasm, endoplasmic reticulum membrane, mitochondrion membrane, nucleus.
GO terms: VRK2 is active in the following subcellular-locations: cytoplasm, endoplasmic reticulum, endoplasmic reticulum membrane, integral component of membrane, mitochondrial membrane, nucleus, protein-containing complex.



UniProt
GO terms

Gene Copy Number Variation


In COSMIC - Cell Lines Project VRK2 has gain in 1 cell-lines, loss in 0 cell-lines and no signal in 1004 cell-lines. (see details)

Gene Expression


In NCI60, the highest expressing cell lines are: SR, K_562, A549

In Array Express (RNA-seq of 675 commonly used human cancer cell lines), the highest expressing cell lines are: NCI-H446, SNU-398, NCI-H1792

In Array Express (RNA-seq of long poly adenylated RNA and long non poly adenylated RNA from ENCODE cell lines), the highest expressing cell lines are: NHLF, A549, NHEK

(see details)

RNA Interference


VRK2 was reported in the following RNAI studies:

Cell - Large Scale Profiling of Kinase Dependencies in Cancer Cell Lines, the highest RNAi cell lines are: COV504, HUO3N1. (see details)

3D Structures


For VRK2 there are:
3 structures (5 chains) solved
2 are solved in complex with at least one small molecule ligand



(see details)
Molecular Target 3D Synopsis

Screening and Chemistry


VRK2 has been screened with 324 compounds (552 bioactivities), 1 compounds have bioactivities that show binding affinity of <= 500nM (1 bioactivities). (see details)