Casein kinase II subunit alpha

UniProt P68400 Organism Homo sapiens Gene CK2A1, CSNK2A1 EC 2.7.11.1

Also known as: CK2A1, CSNK2A1

Function

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. Phosphorylates a number of DNA repair proteins in response to DNA damage, such as MDC1, MRE11, RAD9A, RAD51 and HTATSF1, promoting their recruitment to DNA damage sites. 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. Phosphorylates YY1, protecting YY1 from cleavage by CASP7 during apoptosis. 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, ATF4, SRF, MAX, JUN, FOS, MYC and MYB. Phosphorylates Hsp90 and its co-chaperones FKBP4 and CDC37, which is essential for chaperone function. Mediates sequential phosphorylation of FNIP1, promoting its gradual interaction with Hsp90, leading to activate both kinase and non-kinase client proteins of Hsp90. 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 BMAL1 at 'Ser-90' which is pivotal for its interaction with CLOCK and which controls CLOCK nuclear entry (By similarity). Phosphorylates CCAR2 at 'Thr-454' in gastric carcinoma tissue. Phosphorylates FMR1, promoting FMR1-dependent formation of a membraneless compartment. May phosphorylate histone H2A on 'Ser-1'.

Classification

Family (Pfam): PF00069 Pkinase
InterPro: CK2_alpha, Kinase-like_dom_sf, Prot_kinase_dom, Protein_kinase_ATP_BS, Ser/Thr_kinase_AS
Functional cluster: Phosphoribosyltransferases & related

Experimental structures · PDB · 315

1JWH X-ray 3.10A
1NA7 X-ray 2.40A
1PJK X-ray 2.50A
2PVR X-ray 1.60A
2ZJW X-ray 2.40A
3AMY X-ray 2.30A
3AT2 X-ray 1.60A
3AT3 X-ray 2.60A
3AT4 X-ray 2.20A
3AXW X-ray 2.50A
3BQC X-ray 1.50A
3C13 X-ray 1.95A
… and 303 more

A predicted model is available from AlphaFold.

Gene Ontology · 39

Disease associations

Okur-Chung neurodevelopmental syndrome MONDO:0014893

Drugs targeting this protein · 1

SILMITASERTIB inhibitor

Related proteins · sequence + function similarity

Co-cited proteins · studied together in the literature

Casein kinase II subunit alpha' 18 shared papers
Casein kinase II subunit alpha 3 2 shared papers
Casein kinase II subunit alpha 1 shared papers
Mediator of DNA damage checkpoint protein 1 5 shared papers
Casein kinase II subunit beta 3 shared papers
HIRA-interacting protein 3 1 shared papers
DNA topoisomerase 2-binding protein 1 5 shared papers
RNA-binding protein with serine-rich domain 1 1 shared papers
Casein kinase II subunit alpha 1 shared papers
Cell cycle and apoptosis regulator protein 2 1 shared papers
Cyclic AMP-dependent transcription factor ATF-4 1 shared papers
Nibrin 3 shared papers

Literature · 49 cited papers

Identification and Characterization of HIRIP3 as a Histone H2A Chaperone. Cells · 2024
A PARylation-phosphorylation cascade promotes TOPBP1 loading and RPA-RAD51 exchange in homologous recombination. Mol. Cell · 2022
Phospho-dependent phase separation of FMRP and CAPRIN1 recapitulates regulation of translation and deadenylation. Science · 2019
MDC1 interacts with TOPBP1 to maintain chromosomal stability during mitosis. Mol. Cell · 2019
Phosphoregulated FMRP phase separation models activity-dependent translation through bidirectional control of mRNA granule formation. Proc. Natl. Acad. Sci. U.S.A. · 2019
Post-translational regulation of FNIP1 creates a rheostat for the molecular chaperone Hsp90. Cell Rep. · 2019
Plk1 Phosphorylation of Mre11 Antagonizes the DNA Damage Response. Cancer Res. · 2017
De novo mutations in CSNK2A1 are associated with neurodevelopmental abnormalities and dysmorphic features. Hum. Genet. · 2016
TOPBP1 regulates RAD51 phosphorylation and chromatin loading and determines PARP inhibitor sensitivity. J. Cell Biol. · 2016
CK2alpha phosphorylates DBC1 and is involved in the progression of gastric carcinoma and predicts poor survival of gastric carcinoma patients. Int. J. Cancer · 2015
Functional interaction of protein kinase CK2 and activating transcription factor 4 (ATF4), a key player in the cellular stress response. Biochim. Biophys. Acta · 2013
The SUMO E3-ligase PIAS1 regulates the tumor suppressor PML and its oncogenic counterpart PML-RARA. Cancer Res. · 2012
… and 37 more in the literature graph

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