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 (By similarity). Regulates numerous cellular processes, such as cell cycle progression, apoptosis and transcription, as well as viral infection (By similarity). May act as a regulatory node which integrates and coordinates numerous signals leading to an appropriate cellular response (By similarity). 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 (By similarity). Also required for p53/TP53-mediated apoptosis, phosphorylating 'Ser-392' of p53/TP53 following UV irradiation (By similarity). Can also negatively regulate apoptosis (PubMed:18467326). Phosphorylates the caspases CASP9 and CASP2 and the apoptotic regulator NOL3 (PubMed:18467326). Phosphorylation protects CASP9 from cleavage and activation by CASP8, and inhibits the dimerization of CASP2 and activation of CASP8 (PubMed:18467326). Regulates transcription by direct phosphorylation of RNA polymerases I, II, III and IV (By similarity). Also phosphorylates and regulates numerous transcription factors including NF-kappa-B, STAT1, CREB1, IRF1, IRF2, ATF1, ATF4, SRF, MAX, JUN, FOS, MYC and MYB (By similarity). Phosphorylates Hsp90 and its co-chaperones FKBP4 and CDC37, which is essential for chaperone function (By similarity). Mediates sequential phosphorylation of FNIP1, promoting its gradual interaction with Hsp90, leading to activate both kinase and non-kinase client proteins of Hsp90 (By similarity). Regulates Wnt signaling by phosphorylating CTNNB1 and the transcription factor LEF1 (PubMed:10806215). Acts as an ectokinase that phosphorylates several extracellular proteins (By similarity). During viral infection, phosphorylates various proteins involved in the viral life cycles of EBV, HSV, HBV, HCV, HIV, CMV and HPV (By similarity). Phosphorylates PML at 'Ser-565' and primes it for ubiquitin-mediated degradation (By similarity). 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 (By similarity). ATP + L-seryl-[protein] = ADP + H(+) + O-phospho-L-seryl-[protein] ATP + L-threonyl-[protein] = ADP + H(+) + O-phospho-L-threonyl-[protein] Constitutively active protein kinase whose activity is not directly affected by phosphorylation. Seems to be regulated by level of expression and localization (By similarity). 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 (By similarity). Interacts with RNPS1 (By similarity). Interacts with SNAI1 (PubMed:19923321). Interacts with PML and CCAR2 (By similarity). Phosphorylated at Thr-344, Thr-360, Ser-362 and Ser-370 by CDK1 in prophase and metaphase and dephosphorylated during anaphase. Phosphorylation does not directly affect casein kinase 2 activity, but may contribute to its regulation by forming binding sites for interacting proteins and/or targeting it to different compartments (By similarity). Embryonic lethality at 10.5 dpc. Can use both ATP and GTP as phosphoryl donors. Phosphorylation by casein kinase 2 has been estimated to represent up to one quarter of the eukaryotic phosphoproteome. Belongs to the protein kinase superfamily. Ser/Thr protein kinase family. CK2 subfamily.