NameCasein kinase II subunit alpha
Synonyms
  • 2.7.11.1
  • CK II alpha
  • CK2A1
Gene NameCSNK2A1
OrganismHuman
Amino acid sequence
>lcl|BSEQ0002405|Casein kinase II subunit alpha
MSGPVPSRARVYTDVNTHRPREYWDYESHVVEWGNQDDYQLVRKLGRGKYSEVFEAINIT
NNEKVVVKILKPVKKKKIKREIKILENLRGGPNIITLADIVKDPVSRTPALVFEHVNNTD
FKQLYQTLTDYDIRFYMYEILKALDYCHSMGIMHRDVKPHNVMIDHEHRKLRLIDWGLAE
FYHPGQEYNVRVASRYFKGPELLVDYQMYDYSLDMWSLGCMLASMIFRKEPFFHGHDNYD
QLVRIAKVLGTEDLYDYIDKYNIELDPRFNDILGRHSRKRWERFVHSENQHLVSPEALDF
LDKLLRYDHQSRLTAREAMEHPYFYTVVKDQARMGSSSMPGGSTPVSSANMMSGISSVPT
PSPLGPLAGSPVIAAANPLGMPVPAAAGAQQ
Number of residues391
Molecular Weight45143.25
Theoretical pI7.86
GO Classification
Functions
  • ATP binding
  • protein serine/threonine kinase activity
  • Hsp90 protein binding
  • protein N-terminus binding
Processes
  • Wnt signaling pathway
  • signal transduction
  • chaperone-mediated protein folding
  • positive regulation of Wnt signaling pathway
  • rhythmic process
  • mitotic spindle checkpoint
  • axon guidance
  • regulation of transcription, DNA-templated
  • negative regulation of cysteine-type endopeptidase activity involved in apoptotic process
  • protein phosphorylation
  • positive regulation of cell growth
  • positive regulation of cell proliferation
  • mitotic cell cycle
  • transcription, DNA-templated
  • positive regulation of protein catabolic process
Components
  • NuRD complex
  • nucleus
  • Sin3 complex
  • plasma membrane
  • cytosol
General FunctionProtein serine/threonine kinase activity
Specific FunctionCatalytic 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. 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. 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, SRF, MAX, JUN, FOS, MYC and MYB. Phosphorylates Hsp90 and its co-chaperones FKBP4 and CDC37, which is essential for chaperone function. 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 ARNTL/BMAL1 at 'Ser-90' which is pivotal for its interaction with CLOCK and which controls CLOCK nuclear entry (PubMed:11239457, PubMed:11704824, PubMed:16193064, PubMed:19188443, PubMed:20625391, PubMed:22406621). Phosphorylates CCAR2 at 'Thr-454' in gastric carcinoma tissue (PubMed:24962073).
Pfam Domain Function
Transmembrane RegionsNot Available
GenBank Protein ID598147
UniProtKB IDP68400
UniProtKB Entry NameCSK21_HUMAN
Cellular LocationNucleus
Gene sequence
>lcl|BSEQ0010842|Casein kinase II subunit alpha (CSNK2A1)
ATGTCGGGACCCGTGCCAAGCAGGGCCAGAGTTTACACAGATGTTAATACACACAGACCT
CGAGAATACTGGGATTACGAGTCACATGTGGTGGAATGGGGAAATCAAGATGACTACCAG
CTGGTTCGAAAATTAGGCCGAGGTAAATACAGTGAAGTATTTGAAGCCATCAACATCACA
AATAATGAAAAAGTTGTTGTTAAAATTCTCAAGCCAGTAAAAAAGAAGAAAATTAAGCGT
GAAATAAAGATTTTGGAGAATTTGAGAGGAGGTCCCAACATCATCACACTGGCAGACATT
GTAAAAGACCCTGTGTCACGAACCCCCGCCTTGGTTTTTGAACACGTAAACAACACAGAC
TTCAAGCAATTGTACCAGACGTTAACAGACTATGATATTCGATTTTACATGTATGAGATT
CTGAAGGCCCTGGATTATTGTCACAGCATGGGAATTATGCACAGAGATGTCAAGCCCCAT
AATGTCATGATTGATCATGAGCACAGAAAGCTACGACTAATAGACTGGGGTTTGGCTGAG
TTTTATCATCCTGGCCAAGAATATAATGTCCGAGTTGCTTCCCGATACTTCAAAGGTCCT
GAGCTACTTGTAGACTATCAGATGTACGATTATAGTTTGGATATGTGGAGTTTGGGTTGT
ATGCTGGCAAGTATGATCTTTCGGAAGGAGCCATTTTTCCATGGACATGACAATTATGAT
CAGTTGGTGAGGATAGCCAAGGTTCTGGGGACAGAAGATTTATATGACTATATTGACAAA
TACAACATTGAATTAGATCCACGTTTCAATGATATCTTGGGCAGACACTCTCGAAAGCGA
TGGGAACGCTTTGTCCACAGTGAAAATCAGCACCTTGTCAGCCCTGAGGCCTTGGATTTC
CTGGACAAACTGCTGCGATATGACCACCAGTCACGGCTTACTGCAAGAGAGGCAATGGAG
CACCCCTATTTCTACACTGTTGTGAAGGACCAGGCTCGAATGGGTTCATCTAGCATGCCA
GGGGGCAGTACGCCCGTCAGCAGCGCCAATATGATGTCAGGGATTTCTTCAGTGCCAACC
CCTTCACCCCTTGGACCTCTGGCAGGCTCACCAGTGATTGCTGCTGCCAACCCCCTTGGG
ATGCCTGTTCCAGCTGCCGCTGGCGCTCAGCAGTAA
GenBank Gene IDJ02853
GeneCard IDNot Available
GenAtlas IDCSNK2A1
HGNC IDHGNC:2457
Chromosome Location20
Locus20p13
References
  1. Meisner H, Heller-Harrison R, Buxton J, Czech MP: Molecular cloning of the human casein kinase II alpha subunit. Biochemistry. 1989 May 2;28(9):4072-6. 2752008
  2. Lozeman FJ, Litchfield DW, Piening C, Takio K, Walsh KA, Krebs EG: Isolation and characterization of human cDNA clones encoding the alpha and the alpha' subunits of casein kinase II. Biochemistry. 1990 Sep 11;29(36):8436-47. 2174700
  3. Devilat I, Carvallo P: Structure and sequence of an intronless gene for human casein kinase II-alpha subunit. FEBS Lett. 1993 Jan 25;316(2):114-8. 8420794
  4. Ota T, Suzuki Y, Nishikawa T, Otsuki T, Sugiyama T, Irie R, Wakamatsu A, Hayashi K, Sato H, Nagai K, Kimura K, Makita H, Sekine M, Obayashi M, Nishi T, Shibahara T, Tanaka T, Ishii S, Yamamoto J, Saito K, Kawai Y, Isono Y, Nakamura Y, Nagahari K, Murakami K, Yasuda T, Iwayanagi T, Wagatsuma M, Shiratori A, Sudo H, Hosoiri T, Kaku Y, Kodaira H, Kondo H, Sugawara M, Takahashi M, Kanda K, Yokoi T, Furuya T, Kikkawa E, Omura Y, Abe K, Kamihara K, Katsuta N, Sato K, Tanikawa M, Yamazaki M, Ninomiya K, Ishibashi T, Yamashita H, Murakawa K, Fujimori K, Tanai H, Kimata M, Watanabe M, Hiraoka S, Chiba Y, Ishida S, Ono Y, Takiguchi S, Watanabe S, Yosida M, Hotuta T, Kusano J, Kanehori K, Takahashi-Fujii A, Hara H, Tanase TO, Nomura Y, Togiya S, Komai F, Hara R, Takeuchi K, Arita M, Imose N, Musashino K, Yuuki H, Oshima A, Sasaki N, Aotsuka S, Yoshikawa Y, Matsunawa H, Ichihara T, Shiohata N, Sano S, Moriya S, Momiyama H, Satoh N, Takami S, Terashima Y, Suzuki O, Nakagawa S, Senoh A, Mizoguchi H, Goto Y, Shimizu F, Wakebe H, Hishigaki H, Watanabe T, Sugiyama A, Takemoto M, Kawakami B, Yamazaki M, Watanabe K, Kumagai A, Itakura S, Fukuzumi Y, Fujimori Y, Komiyama M, Tashiro H, Tanigami A, Fujiwara T, Ono T, Yamada K, Fujii Y, Ozaki K, Hirao M, Ohmori Y, Kawabata A, Hikiji T, Kobatake N, Inagaki H, Ikema Y, Okamoto S, Okitani R, Kawakami T, Noguchi S, Itoh T, Shigeta K, Senba T, Matsumura K, Nakajima Y, Mizuno T, Morinaga M, Sasaki M, Togashi T, Oyama M, Hata H, Watanabe M, Komatsu T, Mizushima-Sugano J, Satoh T, Shirai Y, Takahashi Y, Nakagawa K, Okumura K, Nagase T, Nomura N, Kikuchi H, Masuho Y, Yamashita R, Nakai K, Yada T, Nakamura Y, Ohara O, Isogai T, Sugano S: Complete sequencing and characterization of 21,243 full-length human cDNAs. Nat Genet. 2004 Jan;36(1):40-5. Epub 2003 Dec 21. 14702039
  5. Goshima N, Kawamura Y, Fukumoto A, Miura A, Honma R, Satoh R, Wakamatsu A, Yamamoto J, Kimura K, Nishikawa T, Andoh T, Iida Y, Ishikawa K, Ito E, Kagawa N, Kaminaga C, Kanehori K, Kawakami B, Kenmochi K, Kimura R, Kobayashi M, Kuroita T, Kuwayama H, Maruyama Y, Matsuo K, Minami K, Mitsubori M, Mori M, Morishita R, Murase A, Nishikawa A, Nishikawa S, Okamoto T, Sakagami N, Sakamoto Y, Sasaki Y, Seki T, Sono S, Sugiyama A, Sumiya T, Takayama T, Takayama Y, Takeda H, Togashi T, Yahata K, Yamada H, Yanagisawa Y, Endo Y, Imamoto F, Kisu Y, Tanaka S, Isogai T, Imai J, Watanabe S, Nomura N: Human protein factory for converting the transcriptome into an in vitro-expressed proteome,. Nat Methods. 2008 Dec;5(12):1011-7. 19054851
  6. Deloukas P, Matthews LH, Ashurst J, Burton J, Gilbert JG, Jones M, Stavrides G, Almeida JP, Babbage AK, Bagguley CL, Bailey J, Barlow KF, Bates KN, Beard LM, Beare DM, Beasley OP, Bird CP, Blakey SE, Bridgeman AM, Brown AJ, Buck D, Burrill W, Butler AP, Carder C, Carter NP, Chapman JC, Clamp M, Clark G, Clark LN, Clark SY, Clee CM, Clegg S, Cobley VE, Collier RE, Connor R, Corby NR, Coulson A, Coville GJ, Deadman R, Dhami P, Dunn M, Ellington AG, Frankland JA, Fraser A, French L, Garner P, Grafham DV, Griffiths C, Griffiths MN, Gwilliam R, Hall RE, Hammond S, Harley JL, Heath PD, Ho S, Holden JL, Howden PJ, Huckle E, Hunt AR, Hunt SE, Jekosch K, Johnson CM, Johnson D, Kay MP, Kimberley AM, King A, Knights A, Laird GK, Lawlor S, Lehvaslaiho MH, Leversha M, Lloyd C, Lloyd DM, Lovell JD, Marsh VL, Martin SL, McConnachie LJ, McLay K, McMurray AA, Milne S, Mistry D, Moore MJ, Mullikin JC, Nickerson T, Oliver K, Parker A, Patel R, Pearce TA, Peck AI, Phillimore BJ, Prathalingam SR, Plumb RW, Ramsay H, Rice CM, Ross MT, Scott CE, Sehra HK, Shownkeen R, Sims S, Skuce CD, Smith ML, Soderlund C, Steward CA, Sulston JE, Swann M, Sycamore N, Taylor R, Tee L, Thomas DW, Thorpe A, Tracey A, Tromans AC, Vaudin M, Wall M, Wallis JM, Whitehead SL, Whittaker P, Willey DL, Williams L, Williams SA, Wilming L, Wray PW, Hubbard T, Durbin RM, Bentley DR, Beck S, Rogers J: The DNA sequence and comparative analysis of human chromosome 20. Nature. 2001 Dec 20-27;414(6866):865-71. 11780052
  7. Gerhard DS, Wagner L, Feingold EA, Shenmen CM, Grouse LH, Schuler G, Klein SL, Old S, Rasooly R, Good P, Guyer M, Peck AM, Derge JG, Lipman D, Collins FS, Jang W, Sherry S, Feolo M, Misquitta L, Lee E, Rotmistrovsky K, Greenhut SF, Schaefer CF, Buetow K, Bonner TI, Haussler D, Kent J, Kiekhaus M, Furey T, Brent M, Prange C, Schreiber K, Shapiro N, Bhat NK, Hopkins RF, Hsie F, Driscoll T, Soares MB, Casavant TL, Scheetz TE, Brown-stein MJ, Usdin TB, Toshiyuki S, Carninci P, Piao Y, Dudekula DB, Ko MS, Kawakami K, Suzuki Y, Sugano S, Gruber CE, Smith MR, Simmons B, Moore T, Waterman R, Johnson SL, Ruan Y, Wei CL, Mathavan S, Gunaratne PH, Wu J, Garcia AM, Hulyk SW, Fuh E, Yuan Y, Sneed A, Kowis C, Hodgson A, Muzny DM, McPherson J, Gibbs RA, Fahey J, Helton E, Ketteman M, Madan A, Rodrigues S, Sanchez A, Whiting M, Madari A, Young AC, Wetherby KD, Granite SJ, Kwong PN, Brinkley CP, Pearson RL, Bouffard GG, Blakesly RW, Green ED, Dickson MC, Rodriguez AC, Grimwood J, Schmutz J, Myers RM, Butterfield YS, Griffith M, Griffith OL, Krzywinski MI, Liao N, Morin R, Palmquist D, Petrescu AS, Skalska U, Smailus DE, Stott JM, Schnerch A, Schein JE, Jones SJ, Holt RA, Baross A, Marra MA, Clifton S, Makowski KA, Bosak S, Malek J: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. 2004 Oct;14(10B):2121-7. 15489334
  8. Bosc DG, Slominski E, Sichler C, Litchfield DW: Phosphorylation of casein kinase II by p34cdc2. Identification of phosphorylation sites using phosphorylation site mutants in vitro. J Biol Chem. 1995 Oct 27;270(43):25872-8. 7592773
  9. Keller DM, Zeng X, Wang Y, Zhang QH, 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. Mol Cell. 2001 Feb;7(2):283-92. 11239457
  10. Sayed M, Pelech S, Wong C, Marotta A, Salh B: Protein kinase CK2 is involved in G2 arrest and apoptosis following spindle damage in epithelial cells. Oncogene. 2001 Oct 25;20(48):6994-7005. 11704824
  11. Keller DM, Lu H: p53 serine 392 phosphorylation increases after UV through induction of the assembly of the CK2.hSPT16.SSRP1 complex. J Biol Chem. 2002 Dec 20;277(51):50206-13. Epub 2002 Oct 21. 12393879
  12. Shin S, Lee Y, Kim W, Ko H, Choi H, Kim K: Caspase-2 primes cancer cells for TRAIL-mediated apoptosis by processing procaspase-8. EMBO J. 2005 Oct 19;24(20):3532-42. Epub 2005 Sep 29. 16193064
  13. Trembley JH, Tatsumi S, Sakashita E, Loyer P, Slaughter CA, Suzuki H, Endo H, Kidd VJ, Mayeda A: Activation of pre-mRNA splicing by human RNPS1 is regulated by CK2 phosphorylation. Mol Cell Biol. 2005 Feb;25(4):1446-57. 15684395
  14. Daub H, Olsen JV, Bairlein M, Gnad F, Oppermann FS, Korner R, Greff Z, Keri G, Stemmann O, Mann M: Kinase-selective enrichment enables quantitative phosphoproteomics of the kinome across the cell cycle. Mol Cell. 2008 Aug 8;31(3):438-48. doi: 10.1016/j.molcel.2008.07.007. 18691976
  15. St-Denis NA, Derksen DR, Litchfield DW: Evidence for regulation of mitotic progression through temporal phosphorylation and dephosphorylation of CK2alpha. Mol Cell Biol. 2009 Apr;29(8):2068-81. doi: 10.1128/MCB.01563-08. Epub 2009 Feb 2. 19188443
  16. Meggio F, Pinna LA: One-thousand-and-one substrates of protein kinase CK2? FASEB J. 2003 Mar;17(3):349-68. 12631575
  17. Niefind K, Raaf J, Issinger OG: Protein kinase CK2 in health and disease: Protein kinase CK2: from structures to insights. Cell Mol Life Sci. 2009 Jun;66(11-12):1800-16. doi: 10.1007/s00018-009-9149-8. 19387553
  18. St-Denis NA, Litchfield DW: Protein kinase CK2 in health and disease: From birth to death: the role of protein kinase CK2 in the regulation of cell proliferation and survival. Cell Mol Life Sci. 2009 Jun;66(11-12):1817-29. doi: 10.1007/s00018-009-9150-2. 19387552
  19. Filhol O, Cochet C: Protein kinase CK2 in health and disease: Cellular functions of protein kinase CK2: a dynamic affair. Cell Mol Life Sci. 2009 Jun;66(11-12):1830-9. doi: 10.1007/s00018-009-9151-1. 19387551
  20. Miyata Y: Protein kinase CK2 in health and disease: CK2: the kinase controlling the Hsp90 chaperone machinery. Cell Mol Life Sci. 2009 Jun;66(11-12):1840-9. doi: 10.1007/s00018-009-9152-0. 19387550
  21. Dominguez I, Sonenshein GE, Seldin DC: Protein kinase CK2 in health and disease: CK2 and its role in Wnt and NF-kappaB signaling: linking development and cancer. Cell Mol Life Sci. 2009 Jun;66(11-12):1850-7. doi: 10.1007/s00018-009-9153-z. 19387549
  22. MacPherson MR, Molina P, Souchelnytskyi S, Wernstedt C, Martin-Perez J, Portillo F, Cano A: Phosphorylation of serine 11 and serine 92 as new positive regulators of human Snail1 function: potential involvement of casein kinase-2 and the cAMP-activated kinase protein kinase A. Mol Biol Cell. 2010 Jan 15;21(2):244-53. doi: 10.1091/mbc.E09-06-0504. Epub 2009 Nov 18. 19923321
  23. Hung MS, Lin YC, Mao JH, Kim IJ, Xu Z, Yang CT, Jablons DM, You L: Functional polymorphism of the CK2alpha intronless gene plays oncogenic roles in lung cancer. PLoS One. 2010 Jul 2;5(7):e11418. doi: 10.1371/journal.pone.0011418. 20625391
  24. Olsen JV, Vermeulen M, Santamaria A, Kumar C, Miller ML, Jensen LJ, Gnad F, Cox J, Jensen TS, Nigg EA, Brunak S, Mann M: Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis. Sci Signal. 2010 Jan 12;3(104):ra3. doi: 10.1126/scisignal.2000475. 20068231
  25. Burkard TR, Planyavsky M, Kaupe I, Breitwieser FP, Burckstummer T, Bennett KL, Superti-Furga G, Colinge J: Initial characterization of the human central proteome. BMC Syst Biol. 2011 Jan 26;5:17. doi: 10.1186/1752-0509-5-17. 21269460
  26. Rabellino A, Carter B, Konstantinidou G, Wu SY, Rimessi A, Byers LA, Heymach JV, Girard L, Chiang CM, Teruya-Feldstein J, Scaglioni PP: The SUMO E3-ligase PIAS1 regulates the tumor suppressor PML and its oncogenic counterpart PML-RARA. Cancer Res. 2012 May 1;72(9):2275-84. doi: 10.1158/0008-5472.CAN-11-3159. Epub 2012 Mar 9. 22406621
  27. Bae JS, Park SH, Kim KM, Kwon KS, Kim CY, Lee HK, Park BH, Park HS, Lee H, Moon WS, Chung MJ, Sylvester KG, Jang KY: CK2alpha phosphorylates DBC1 and is involved in the progression of gastric carcinoma and predicts poor survival of gastric carcinoma patients. Int J Cancer. 2015 Feb 15;136(4):797-809. doi: 10.1002/ijc.29043. Epub 2014 Jul 1. 24962073
  28. Niefind K, Guerra B, Ermakowa I, Issinger OG: Crystallization and preliminary characterization of crystals of human protein kinase CK2. Acta Crystallogr D Biol Crystallogr. 2000 Dec;56(Pt 12):1680-4. 11092945
  29. Niefind K, Guerra B, Ermakowa I, Issinger OG: Crystal structure of human protein kinase CK2: insights into basic properties of the CK2 holoenzyme. EMBO J. 2001 Oct 1;20(19):5320-31. 11574463
  30. Pechkova E, Zanotti G, Nicolini C: Three-dimensional atomic structure of a catalytic subunit mutant of human protein kinase CK2. Acta Crystallogr D Biol Crystallogr. 2003 Dec;59(Pt 12):2133-9. Epub 2003 Nov 27. 14646071
  31. Ermakova I, Boldyreff B, Issinger OG, Niefind K: Crystal structure of a C-terminal deletion mutant of human protein kinase CK2 catalytic subunit. J Mol Biol. 2003 Jul 25;330(5):925-34. 12860116