CSNK2A1
Description
The CSNK2A1 (casein kinase 2 alpha 1) is a protein-coding gene located on chromosome 20.
Casein kinase II subunit alpha is an enzyme that in humans is encoded by the CSNK2A1 gene. Casein kinase II is a serine/threonine protein kinase that phosphorylates acidic proteins such as casein. The kinase exists as a tetramer and is composed of an alpha, an alpha-prime, and two beta subunits. The alpha subunits contain the catalytic activity while the beta subunits undergo autophosphorylation. The protein encoded by this gene represents the alpha subunit. While this gene is found on chromosome 20, a related transcribed pseudogene is found on chromosome 11. Three transcript variants encoding two different proteins have been found for this gene.
The protein encoded by the CSNK2A1 gene is a catalytic subunit of a constitutively active serine/threonine-protein kinase complex. This complex phosphorylates a wide range of substrates, particularly those containing acidic residues C-terminal to the phosphorylated serine or threonine. CSNK2A1 plays a crucial role in regulating numerous cellular processes including cell cycle progression, apoptosis, transcription, and viral infection. It acts as a regulatory node integrating and coordinating signals leading to appropriate cellular responses. During mitosis, CSNK2A1 is part of the p53/TP53-dependent spindle assembly checkpoint (SAC), ensuring proper chromosome segregation. It also contributes to p53/TP53-mediated apoptosis by phosphorylating 'Ser-392' of p53/TP53 following UV irradiation. In response to DNA damage, CSNK2A1 phosphorylates several DNA repair proteins, such as MDC1, MRE11, RAD9A, RAD51 and HTATSF1, facilitating their recruitment to DNA damage sites. CSNK2A1 can also negatively regulate apoptosis by phosphorylating the caspases CASP9 and CASP2 and the apoptotic regulator NOL3. This phosphorylation prevents CASP9 cleavage and activation by CASP8, and inhibits CASP2 dimerization and CASP8 activation. CSNK2A1 regulates transcription by directly phosphorylating RNA polymerases I, II, III and IV, and it also phosphorylates and regulates numerous transcription factors, including NF-kappa-B, STAT1, CREB1, IRF1, IRF2, ATF1, ATF4, SRF, MAX, JUN, FOS, MYC and MYB. It further phosphorylates Hsp90 and its co-chaperones FKBP4 and CDC37, essential for chaperone function. CSNK2A1 mediates sequential phosphorylation of FNIP1, promoting its gradual interaction with Hsp90, activating both kinase and non-kinase client proteins of Hsp90. It regulates Wnt signaling by phosphorylating CTNNB1 and the transcription factor LEF1. CSNK2A1 acts as an ectokinase, phosphorylating several extracellular proteins. During viral infection, it phosphorylates various proteins involved in the viral life cycles of EBV, HSV, HBV, HCV, HIV, CMV and HPV. CSNK2A1 phosphorylates PML at 'Ser-565' priming it for ubiquitin-mediated degradation. It plays a key role in circadian clock function by phosphorylating BMAL1 at 'Ser-90', crucial for BMAL1's interaction with CLOCK and controlling CLOCK nuclear entry. CSNK2A1 phosphorylates CCAR2 at 'Thr-454' in gastric carcinoma tissue. It also phosphorylates FMR1, promoting FMR1-dependent formation of a membraneless compartment.
CSNK2A1 is also known as CK2A1, CKII, Cka1, Cka2, OCNDS.
