Alternative titles; symbols
HGNC Approved Gene Symbol: CSNK2A2
Cytogenetic location: 16q21 Genomic coordinates (GRCh38) : 16:58,157,907-58,198,106 (from NCBI)
Casein kinase II catalyzes the phosphorylation of serine or threonine residues in proteins; i.e., it is a protein serine/threonine kinase. The enzyme is probably present in all eukaryotic cells, implying that it has fundamental cellular functions. The holoenzyme is a tetramer containing 2 alpha or alpha-prime subunits (or one of each) and 2 beta subunits. The function of the beta subunit is unknown but presumably it fills a regulatory role in the holoenzyme. The alpha subunit is the catalytic subunit. Lozeman et al. (1990) reported studies indicating that the 2 catalytic subunits, alpha and alpha-prime, have distinct sequences and that these sequences are largely conserved between the bovine and the human.
Phosphorylation of the human p53 protein (191170) at ser392 is responsive to ultraviolet (UV) but not gamma irradiation. Keller et al. (2001) identified and purified a mammalian UV-activated protein kinase complex that phosphorylates ser392 in vitro. This kinase complex contains CK2 and the chromatin transcriptional elongation factor FACT, a heterodimer of SPT16 (605012) and SSRP1 (604328). In vitro studies showed that FACT alters the specificity of CK2 in the complex such that it selectively phosphorylates p53 over other substrates, including casein. In addition, phosphorylation by the kinase complex was found to enhance p53 activity. These results provided a potential mechanism for p53 activation by UV irradiation.
Doray et al. (2002) demonstrated that the Golgi-localized, gamma-ear-containing adenosine diphosphate ribosylation factor-binding proteins (GGA1, 606004 and GGA3, 606006) and the coat protein adaptor protein-1 (AP-1) complex (see AP1G2, 603534) colocalize in clathrin-coated buds of the trans-Golgi networks of mouse L cells and human HeLa cells. Binding studies revealed a direct interaction between the hinge domains of the GGAs and the gamma-ear domain of AP-1. Further, AP-1 contained bound casein kinase-2 that phosphorylated GGA1 and GGA3, thereby causing autoinhibition. Doray et al. (2002) demonstrated that this autoinhibition could induce the directed transfer of mannose 6-phosphate receptors (see 154540) from the GGAs to AP-1. Mannose 6-phosphate receptors that were defective in binding to GGAs were poorly incorporated into adaptor protein complex containing clathrin coated vesicles. Thus, Doray et al. (2002) concluded that GGAs and the AP-1 complex interact to package mannose 6-phosphate receptors into AP-1-containing coated vesicles.
By yeast 2-hybrid analysis of an adult human heart cDNA library, Hauck et al. (2008) showed that p27 (CDKN1B; 600778) interacted with the C-terminal region of CK2-alpha-prime. Immunocytochemical analysis of primary rat ventricular cardiomyocytes revealed colocalization of p27 with CK2-alpha-prime. Hauck et al. (2008) found that angiotensin II (106150), a potent inducer of cardiomyocyte hypertrophy, induced proteasomal degradation of p27 in primary rat cardiomyocytes through CK2-alpha-prime-dependent phosphorylation of p27 on ser83 and thr187, which are conserved in human and rodents. Conversely, unphosphorylated p27 potently inhibited CK2-alpha-prime. Hauck et al. (2008) concluded that downregulation of p27 by CK2-alpha-prime is necessary for development of agonist- and stress-induced cardiac hypertrophy.
By somatic cell hybrid analysis, Yang-Feng et al. (1991) demonstrated that the CK2A2 gene maps to chromosome 16. By in situ hybridization, Yang-Feng et al. (1994) mapped the CSNK2A2 gene to 16p13.3-p13.2. (In the title and body of the article, Yang-Feng et al. (1994) incorrectly referred to the gene in question as CSNK2A1; CSNK2A1 (115440) is located on 20p13.)
To determine the functional and developmental role of protein kinase casein kinase II, Xu et al. (1999) used homologous recombination to disrupt the gene encoding Csnk2a2 in transgenic mice. They found that Csnk2a2 is preferentially expressed in late stages of spermatogenesis, and male mice in which Csnk2a2 has been disrupted are infertile, with oligospermia and globozoospermia ('round-headed spermatozoa'). This was the first demonstration of the unique role for a Ck2 isoform in development. The primary spermatogenic defect in the Csnk2a2 -/- testis is a specific abnormality of anterior head shaping of elongating spermatids; this is the first defined gene that regulates sperm head morphogenesis. As the germ cells differentiate, they are capable of undergoing chromatin condensation, although many abnormal cells are deleted through apoptosis or Sertoli cell phagocytosis. The few that survived to populate the epididymis exhibited head abnormalities similar to those described in human globozoospermia; thus, Csnk2a2 may be a candidate gene for inherited abnormalities of sperm morphogenesis.
Lin et al. (2002) identified a Drosophila circadian mutant, Timekeeper (Tik), that behaved in a dominant manner. Tik homozygotes do not live to adulthood, and heterozygotes have a circadian rhythm lengthened by about 3 hours. Lin et al. (2002) showed that the catalytic subunit of Drosophila casein kinase-2 (CK2-alpha) is expressed predominantly in the cytoplasm of key circadian pacemaker neurons. CK2-alpha mutant flies showed lengthened circadian period, decreased CK2 activity, and delayed nuclear entry of Per (see 602260). Lin et al. (2002) suggested that these are probably direct, as CK2-alpha specifically phosphorylates Per in vitro. Lin et al. (2002) proposed that CK2 is an evolutionary link between the divergent circadian systems of animals, plants, and fungi.
Doray, B., Ghosh, P., Griffith, J., Geuze, H. J., Kornfeld, S. Cooperation of GGAs and AP-1 in packaging MPRs at the trans-Golgi network. Science 297: 1700-1703, 2002. [PubMed: 12215646] [Full Text: https://doi.org/10.1126/science.1075327]
Hauck, L., Harms, C., An, J., Rohne, J., Gertz, K., Dietz, R., Endres, M., von Harsdorf, R. Protein kinase CK2 links extracellular growth factor signaling with the control of p27(Kip1) stability in the heart. Nature Med. 14: 315-324, 2008. Note: Erratum: Nature Med. 14: 585 only, 2008. [PubMed: 18311148] [Full Text: https://doi.org/10.1038/nm1729]
Keller, D. M., Zeng, X., Wang, Y., Zhang, Q. H., Kapoor, M., Shu, H., Goodman, R., Lozano, G., Zhao, Y., Lu, H. A DNA damage-induced p53 serine 392 kinase complex contains CK2, hSpt16, and SSRP1. Molec. Cell 7: 283-292, 2001. [PubMed: 11239457] [Full Text: https://doi.org/10.1016/s1097-2765(01)00176-9]
Lin, J.-M., Kilman, V. L., Keegan, K., Paddock, B., Emery-Le, M., Rosbash, M., Allada, R. A role for casein kinase 2-alpha in the Drosophila circadian clock. Nature 420: 816-820, 2002. [PubMed: 12447397] [Full Text: https://doi.org/10.1038/nature01235]
Lozeman, F. J., Litchfield, D. W., Piening, C., Takio, K., Walsh, K. A., Krebs, E. G. Isolation and characterization of human cDNA clones encoding the alpha and the alpha-prime subunits of casein kinase II. Biochemistry 29: 8436-8447, 1990. [PubMed: 2174700] [Full Text: https://doi.org/10.1021/bi00488a034]
Xu, X., Toselli, P. A., Russell, L. D., Seldin, D. C. Globozoospermia in mice lacking the casein kinase II alpha-prime catalytic subunit. Nature Genet. 23: 118-121, 1999. [PubMed: 10471512] [Full Text: https://doi.org/10.1038/12729]
Yang-Feng, T. L., Naiman, T., Kopatz, I., Eli, D., Dafni, N., Canaani, D. Assignment of the human casein kinase II alpha-prime subunit gene (CSNK2A1) to chromosome 16p13.2-p13.3. Genomics 19: 173 only, 1994. [PubMed: 8188223] [Full Text: https://doi.org/10.1006/geno.1994.1032]
Yang-Feng, T. L., Zheng, K., Kopatz, I., Naiman, T., Canaani, D. Mapping of the human casein kinase II catalytic subunit genes: two loci carrying the homologous sequences for the alpha subunit. Nucleic Acids Res. 19: 7125-7129, 1991. [PubMed: 1766873] [Full Text: https://doi.org/10.1093/nar/19.25.7125]