Casein kinase II subunit alpha (CSNK2A1)
The protein contains 391 amino acids for an estimated molecular weight of 45144 Da.
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 (PubMed:11239457, PubMed:11704824, PubMed:16193064, PubMed:19188443, PubMed:20625391, PubMed:22406621, PubMed:24962073). Regulates numerous cellular processes, such as cell cycle progression, apoptosis and transcription, as well as viral infection (PubMed:12631575, PubMed:19387552, PubMed:19387551). May act as a regulatory node which integrates and coordinates numerous signals leading to an appropriate cellular response (PubMed:12631575, PubMed:19387552, PubMed:19387551). 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 (PubMed:11704824, PubMed:19188443). Also required for p53/TP53-mediated apoptosis, phosphorylating 'Ser-392' of p53/TP53 following UV irradiation. Can also negatively regulate apoptosis (PubMed:11239457). Phosphorylates the caspases CASP9 and CASP2 and the apoptotic regulator NOL3 (PubMed:16193064). Phosphorylation protects CASP9 from cleavage and activation by CASP8, and inhibits the dimerization of CASP2 and activation of CASP8 (PubMed:16193064). Regulates transcription by direct phosphorylation of RNA polymerases I, II, III and IV. Also phosphorylates and regulates numerous transcription factors including NF-kappa- (updated: April 22, 2020)
Protein identification was indicated in the following studies:
- Goodman and co-workers. (2013) The proteomics and interactomics of human erythrocytes. Exp Biol Med (Maywood) 238(5), 509-518.
- Hegedűs and co-workers. (2015) Inconsistencies in the red blood cell membrane proteome analysis: generation of a database for research and diagnostic applications. Database (Oxford) 1-8.
- Bryk and co-workers. (2017) Quantitative Analysis of Human Red Blood Cell Proteome. J Proteome Res. 16(8), 2752-2761.
- D'Alessandro and co-workers. (2017) Red blood cell proteomics update: is there more to discover? Blood Transfus. 15(2), 182-187.
Methods
The following articles were analysed to gather the proteome content of erythrocytes.
The gene or protein list provided in the studies were processed using the ID mapping API of Uniprot in September 2018. The number of proteins identified and mapped without ambiguity in these studies is indicated below.
Only Swiss-Prot entries (reviewed) were considered for protein evidence assignation.
| Publication | Identification 1 | Uniprot mapping 2 | Not mapped / Obsolete | TrEMBL | Swiss-Prot |
|---|---|---|---|---|---|
| Goodman (2013) | 2289 (gene list) | 2278 | 53 | 20599 | 2269 |
| Lange (2014) | 1234 | 1234 | 7 | 28 | 1224 |
| Hegedus (2015) | 2638 | 2622 | 0 | 235 | 2387 |
| Wilson (2016) | 1658 | 1528 | 170 | 291 | 1068 |
| d'Alessandro (2017) | 1826 | 1817 | 2 | 0 | 1815 |
| Bryk (2017) | 2090 | 2060 | 10 | 108 | 1942 |
| Chu (2018) | 1853 | 1804 | 55 | 362 | 1387 |
1 as available in the article and/or in supplementary material
2 uniprot mapping returns all protein isoforms as one entry
The compilation of older studies can be retrieved from the Red Blood Cell Collection database.
The data and differentiation stages presented below come from the proteomic study and analysis performed by our partners of the GReX consortium, more details are available in their published work.
This protein is annotated as membranous in Gene Ontology.
Biological Process
Apoptotic process
Axon guidance
Cell cycle
Cerebral cortex development
Chaperone-mediated protein folding
Liver regeneration
Macroautophagy
Mitotic cell cycle
Mitotic chromosome condensation
Mitotic spindle checkpoint
Negative regulation of apoptotic signaling pathway
Negative regulation of cysteine-type endopeptidase activity involved in apoptotic process
Negative regulation of ubiquitin-dependent protein catabolic process
Peptidyl-serine phosphorylation
Peptidyl-threonine phosphorylation
Phosphatidylcholine biosynthetic process
Positive regulation of cell growth
Positive regulation of cell population proliferation
Positive regulation of protein catabolic process
Positive regulation of Wnt signaling pathway
Protein folding
Protein phosphorylation
Regulation of cell cycle
Regulation of chromosome separation
Regulation of protein localization to plasma membrane
Regulation of signal transduction by p53 class mediator
Regulation of transcription, DNA-templated
Response to testosterone
Rhythmic process
Signal transduction
Transcription, DNA-templated
Wnt signaling pathway
Cellular Component
Chromatin
Cytosol
Nucleoplasm
Nucleus
NuRD complex
Plasma membrane
Protein kinase CK2 complex
Sin3 complex
The reference OMIM entry for this protein is 115440
Casein kinase ii, alpha-1; csnk2a1
Casein kinase ii, alpha subunit; ck2a1
CLONING
Casein kinase II is a serine/threonine kinase that phosphorylates acidic protein such as casein. It has a tetrameric a(2)/b(2) structure. The alpha subunit of molecular mass 40 kD possesses catalytic activity, whereas the beta subunit (115441), molecular mass 25 kD, is autophosphorylated in vitro. Meisner et al. (1989) reported the identification and nucleotide sequencing of a complete human cDNA for the alpha subunit. Using the full-length cDNA probe, Meisner et al. (1989) found 2 bands with restriction enzymes that have no recognition sites within the cDNA and 3 to 6 bands with enzymes having single internal sites. These results were considered consistent with the existence of 2 genes encoding alpha subunits. See 115442.GENE STRUCTURE
Wirkner et al. (1994) demonstrated that the CSNK2A1 gene contains 8 exons whose sequences comprise bases 102 to 824 of the coding region of the human casein kinase II alpha subunit. Three of the 9 introns are located at positions corresponding to those of the homologous gene in the nematode Caenorhabditis elegans. The introns contain 8 complete and 8 incomplete Alu repeats.GENE FUNCTION
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. 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 a ... More on the omim web site
April 25, 2020: Protein entry updated
Automatic update: Entry updated from uniprot information.
Feb. 2, 2018: Protein entry updated
Automatic update: Uniprot description updated
Dec. 19, 2017: Protein entry updated
Automatic update: Uniprot description updated
Nov. 23, 2017: Protein entry updated
Automatic update: Uniprot description updated
March 25, 2017: Additional information
No protein expression data in P. Mayeux work for CSNK2A1
March 16, 2016: Protein entry updated
Automatic update: OMIM entry 115440 was added.
Jan. 27, 2016: Protein entry updated
Automatic update: model status changed
Jan. 24, 2016: Protein entry updated
Automatic update: model status changed