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

CSNK2A1 (P68400) - Overview - Molecular Target Synopsis

Protein


CSNK2A1, Casein kinase II subunit alpha
Enzyme Classification 2.7.11.1
UniProt P68400

Also Known as CSK21_HUMAN, CSNK2A1, CK2A1

Catalytic subunit of a constitutively active serine/threonine-protein kinase complex that phosphorylates a large number of substrates containing acidic residues C-terminal to the phosphorylated serine or threonine. Regulates numerous cellular processes, such as cell cycle progression, apoptosis and transcription, as well as viral infection. May act as a regulatory node which integrates and coordinates numerous signals leading to an appropriate cellular response. During mitosis, functions as a component of the p53/TP53-dependent spindle assembly checkpoint (SAC) that maintains cyclin-B-CDK1 activity and G2 arrest in response to spindle damage. Also required for p53/TP53-mediated apoptosis, phosphorylating 'Ser-392' of p53/TP53 following UV irradiation. Can also negatively regulate apoptosis. Phosphorylates the caspases CASP9 and CASP2 and the apoptotic regulator NOL3. Phosphorylation protects CASP9 from cleavage and activation by CASP8, and inhibits the dimerization of CASP2 and activation of CASP8. Regulates transcription by direct phosphorylation of RNA polymerases I, II, III and IV. Also phosphorylates and regulates numerous transcription factors including NF-kappa-B, STAT1, CREB1, IRF1, IRF2, ATF1, SRF, MAX, JUN, FOS, MYC and MYB. Phosphorylates Hsp90 and its co-chaperones FKBP4 and CDC37, which is essential for chaperone function. Regulates Wnt signaling by phosphorylating CTNNB1 and the transcription factor LEF1. Acts as an ectokinase that phosphorylates several extracellular proteins. During viral infection, phosphorylates various proteins involved in the viral life cycles of EBV, HSV, HBV, HCV, HIV, CMV and HPV. Phosphorylates PML at 'Ser-565' and primes it for ubiquitin-mediated degradation. Plays an important role in the circadian clock function by phosphorylating ARNTL/BMAL1 at 'Ser-90' which is pivotal for its interaction with CLOCK and which controls CLOCK nuclear entry (PubMed:11239457, PubMed:11704824, PubMed:16193064, PubMed:19188443, PubMed:20625391, PubMed:22406621). Phosphorylates CCAR2 at 'Thr-454' in gastric carcinoma tissue (PubMed:24962073). Heterotetramer composed of two catalytic subunits (alpha chain and/or alpha' chain) and two regulatory subunits (beta chains). The tetramer can exist as a combination of 2 alpha/2 beta, 2 alpha'/2 beta or 1 alpha/1 alpha'/2 beta subunits. Also part of a CK2-SPT16-SSRP1 complex composed of SSRP1, SUPT16H, CSNK2A1, CSNK2A2 and CSNK2B, which forms following UV irradiation. Interacts with RNPS1. Interacts with SNAI1. Interacts with PML (isoform PML-12). Interacts with CCAR2.

6JWA
CRYSTAL STRUCTURE OF CK2A1 WITH 5-IODOTUBERCIDIN
RCSB/PDB
Inspect Structure
See all 3D Structures for CSNK2A1

Isoforms / Transcripts (Protein Coding)


Sub-cellular localization


UniProt: CSNK2A1 is active in the following subcellular-locations: nucleus.
GO terms: CSNK2A1 is active in the following subcellular-locations: cytosol, nucleoplasm, nucleus, NuRD complex, plasma membrane, protein kinase CK2 complex, Sin3 complex.



UniProt
GO terms

Gene Copy Number Variation


In COSMIC - Cell Lines Project CSNK2A1 has gain in 1 cell-lines, loss in 3 cell-lines and no signal in 1001 cell-lines. (see details)

Gene Expression


In NCI60, the highest expressing cell lines are: HOP_62, TK_10, ACHN

In Array Express (RNA-seq of 675 commonly used human cancer cell lines), the highest expressing cell lines are: Hs 746T, HCC38, SNU-1

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, HSMM, SK-N-SH

(see details)

RNA Interference


CSNK2A1 was reported in the following RNAI studies:

Cell - Large Scale Profiling of Kinase Dependencies in Cancer Cell Lines, the highest RNAi cell lines are: TE10, MDAMB436. (see details)

3D Structures


For CSNK2A1 there are:
162 structures (253 chains) solved
140 are solved in complex with at least one small molecule ligand
3 are solved with an approved drug

CSNK2A1 is solved in complex with the approved drug(s):

NIO/NIACIN (3WAR_A),
BEZ/BENZOIC ACID (6Q38_A, 6Q4Q_A, 6Q4Q_B).

(see details)
Molecular Target 3D Synopsis

Screening and Chemistry


CSNK2A1 has been screened with 2249 compounds (3605 bioactivities), 606 compounds have bioactivities that show binding affinity of <= 500nM (847 bioactivities). (see details)