Full text data of CSNK2A2
CSNK2A2
(CK2A2)
[Confidence: low (only semi-automatic identification from reviews)]
Casein kinase II subunit alpha'; CK II alpha'; 2.7.11.1
Note: presumably soluble (membrane word is not in UniProt keywords or features)
Casein kinase II subunit alpha'; CK II alpha'; 2.7.11.1
Note: presumably soluble (membrane word is not in UniProt keywords or features)
UniProt
P19784
ID CSK22_HUMAN Reviewed; 350 AA.
AC P19784;
DT 01-FEB-1991, integrated into UniProtKB/Swiss-Prot.
read moreDT 01-FEB-1991, sequence version 1.
DT 22-JAN-2014, entry version 147.
DE RecName: Full=Casein kinase II subunit alpha';
DE Short=CK II alpha';
DE EC=2.7.11.1;
GN Name=CSNK2A2; Synonyms=CK2A2;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=2174700; DOI=10.1021/bi00488a034;
RA Lozeman F.J., Litchfield D.W., Piening C., Takio K., Walsh K.A.,
RA Krebs E.G.;
RT "Isolation and characterization of human cDNA clones encoding the
RT alpha and the alpha' subunits of casein kinase II.";
RL Biochemistry 29:8436-8447(1990).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Ovary;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [3]
RP FUNCTION, AND INTERACTION WITH SSRP1 AND SUPT16H.
RX PubMed=11239457; DOI=10.1016/S1097-2765(01)00176-9;
RA Keller D.M., Zeng X., Wang Y., Zhang Q.H., Kapoor M., Shu H.,
RA Goodman R., Lozano G., Zhao Y., Lu H.;
RT "A DNA damage-induced p53 serine 392 kinase complex contains CK2,
RT hSpt16, and SSRP1.";
RL Mol. Cell 7:283-292(2001).
RN [4]
RP FUNCTION IN CELL CYCLE.
RX PubMed=11704824; DOI=10.1038/sj.onc.1204894;
RA Sayed M., Pelech S., Wong C., Marotta A., Salh B.;
RT "Protein kinase CK2 is involved in G2 arrest and apoptosis following
RT spindle damage in epithelial cells.";
RL Oncogene 20:6994-7005(2001).
RN [5]
RP INTERACTION WITH SSRP1 AND SUPT16H.
RX PubMed=12393879; DOI=10.1074/jbc.M209820200;
RA Keller D.M., Lu H.;
RT "p53 serine 392 phosphorylation increases after UV through induction
RT of the assembly of the CK2.hSPT16.SSRP1 complex.";
RL J. Biol. Chem. 277:50206-50213(2002).
RN [6]
RP FUNCTION IN APOPTOSIS.
RX PubMed=16193064; DOI=10.1038/sj.emboj.7600827;
RA Shin S., Lee Y., Kim W., Ko H., Choi H., Kim K.;
RT "Caspase-2 primes cancer cells for TRAIL-mediated apoptosis by
RT processing procaspase-8.";
RL EMBO J. 24:3532-3542(2005).
RN [7]
RP REVIEW ON FUNCTION.
RX PubMed=12631575; DOI=10.1096/fj.02-0473rev;
RA Meggio F., Pinna L.A.;
RT "One-thousand-and-one substrates of protein kinase CK2?";
RL FASEB J. 17:349-368(2003).
RN [8]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-18; SER-21 AND SER-288,
RP AND MASS SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=18691976; DOI=10.1016/j.molcel.2008.07.007;
RA Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R.,
RA Greff Z., Keri G., Stemmann O., Mann M.;
RT "Kinase-selective enrichment enables quantitative phosphoproteomics of
RT the kinome across the cell cycle.";
RL Mol. Cell 31:438-448(2008).
RN [9]
RP REVIEW ON STRUCTURE.
RX PubMed=19387553; DOI=10.1007/s00018-009-9149-8;
RA Niefind K., Raaf J., Issinger O.G.;
RT "Protein kinase CK2 in health and disease: Protein kinase CK2: from
RT structures to insights.";
RL Cell. Mol. Life Sci. 66:1800-1816(2009).
RN [10]
RP REVIEW ON FUNCTION.
RX PubMed=19387552; DOI=10.1007/s00018-009-9150-2;
RA St-Denis N.A., Litchfield D.W.;
RT "Protein kinase CK2 in health and disease: From birth to death: the
RT role of protein kinase CK2 in the regulation of cell proliferation and
RT survival.";
RL Cell. Mol. Life Sci. 66:1817-1829(2009).
RN [11]
RP REVIEW ON FUNCTION.
RX PubMed=19387551; DOI=10.1007/s00018-009-9151-1;
RA Filhol O., Cochet C.;
RT "Protein kinase CK2 in health and disease: Cellular functions of
RT protein kinase CK2: a dynamic affair.";
RL Cell. Mol. Life Sci. 66:1830-1839(2009).
RN [12]
RP REVIEW ON FUNCTION IN REGULATION OF HSP90.
RX PubMed=19387550; DOI=10.1007/s00018-009-9152-0;
RA Miyata Y.;
RT "Protein kinase CK2 in health and disease: CK2: the kinase controlling
RT the Hsp90 chaperone machinery.";
RL Cell. Mol. Life Sci. 66:1840-1849(2009).
RN [13]
RP REVIEW ON FUNCTION IN WNT SIGNALING.
RX PubMed=19387549; DOI=10.1007/s00018-009-9153-z;
RA Dominguez I., Sonenshein G.E., Seldin D.C.;
RT "Protein kinase CK2 in health and disease: CK2 and its role in Wnt and
RT NF-kappaB signaling: linking development and cancer.";
RL Cell. Mol. Life Sci. 66:1850-1857(2009).
RN [14]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-13; SER-18; SER-21 AND
RP SER-288, AND MASS SPECTROMETRY.
RX PubMed=19369195; DOI=10.1074/mcp.M800588-MCP200;
RA Oppermann F.S., Gnad F., Olsen J.V., Hornberger R., Greff Z., Keri G.,
RA Mann M., Daub H.;
RT "Large-scale proteomics analysis of the human kinome.";
RL Mol. Cell. Proteomics 8:1751-1764(2009).
RN [15]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-97, AND MASS SPECTROMETRY.
RX PubMed=19608861; DOI=10.1126/science.1175371;
RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M.,
RA Walther T.C., Olsen J.V., Mann M.;
RT "Lysine acetylation targets protein complexes and co-regulates major
RT cellular functions.";
RL Science 325:834-840(2009).
RN [16]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P.,
RA Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [17]
RP X-RAY CRYSTALLOGRAPHY (3.20 ANGSTROMS) OF 1-334 IN COMPLEX WITH
RP INHIBITOR.
RX PubMed=19193990; DOI=10.1107/S1744309108043194;
RA Nakaniwa T., Kinoshita T., Sekiguchi Y., Tada T., Nakanishi I.,
RA Kitaura K., Suzuki Y., Ohno H., Hirasawa A., Tsujimoto G.;
RT "Structure of human protein kinase CK2 alpha 2 with a potent indazole-
RT derivative inhibitor.";
RL Acta Crystallogr. F 65:75-79(2009).
RN [18]
RP X-RAY CRYSTALLOGRAPHY (2.00 ANGSTROMS).
RX PubMed=21241709; DOI=10.1016/j.jmb.2011.01.020;
RA Bischoff N., Olsen B., Raaf J., Bretner M., Issinger O.G., Niefind K.;
RT "Structure of the human protein kinase CK2 catalytic subunit CK2alpha'
RT and interaction thermodynamics with the regulatory subunit CK2beta.";
RL J. Mol. Biol. 407:1-12(2011).
RN [19]
RP VARIANT [LARGE SCALE ANALYSIS] ALA-188.
RX PubMed=17344846; DOI=10.1038/nature05610;
RA Greenman C., Stephens P., Smith R., Dalgliesh G.L., Hunter C.,
RA Bignell G., Davies H., Teague J., Butler A., Stevens C., Edkins S.,
RA O'Meara S., Vastrik I., Schmidt E.E., Avis T., Barthorpe S.,
RA Bhamra G., Buck G., Choudhury B., Clements J., Cole J., Dicks E.,
RA Forbes S., Gray K., Halliday K., Harrison R., Hills K., Hinton J.,
RA Jenkinson A., Jones D., Menzies A., Mironenko T., Perry J., Raine K.,
RA Richardson D., Shepherd R., Small A., Tofts C., Varian J., Webb T.,
RA West S., Widaa S., Yates A., Cahill D.P., Louis D.N., Goldstraw P.,
RA Nicholson A.G., Brasseur F., Looijenga L., Weber B.L., Chiew Y.-E.,
RA DeFazio A., Greaves M.F., Green A.R., Campbell P., Birney E.,
RA Easton D.F., Chenevix-Trench G., Tan M.-H., Khoo S.K., Teh B.T.,
RA Yuen S.T., Leung S.Y., Wooster R., Futreal P.A., Stratton M.R.;
RT "Patterns of somatic mutation in human cancer genomes.";
RL Nature 446:153-158(2007).
CC -!- FUNCTION: Catalytic subunit of a constitutively active
CC serine/threonine-protein kinase complex that phosphorylates a
CC large number of substrates containing acidic residues C-terminal
CC to the phosphorylated serine or threonine. Regulates numerous
CC cellular processes, such as cell cycle progression, apoptosis and
CC transcription, as well as viral infection. May act as a regulatory
CC node which integrates and coordinates numerous signals leading to
CC an appropriate cellular response. During mitosis, functions as a
CC component of the p53/TP53-dependent spindle assembly checkpoint
CC (SAC) that maintains cyclin-B-CDK1 activity and G2 arrest in
CC response to spindle damage. Also required for p53/TP53-mediated
CC apoptosis, phosphorylating 'Ser-392' of p53/TP53 following UV
CC irradiation. Can also negatively regulate apoptosis.
CC Phosphorylates the caspases CASP9 and CASP2 and the apoptotic
CC regulator NOL3. Phosphorylation protects CASP9 from cleavage and
CC activation by CASP8, and inhibits the dimerization of CASP2 and
CC activation of CASP8. Regulates transcription by direct
CC phosphorylation of RNA polymerases I, II, III and IV. Also
CC phosphorylates and regulates numerous transcription factors
CC including NF-kappa-B, STAT1, CREB1, IRF1, IRF2, ATF1, SRF, MAX,
CC JUN, FOS, MYC and MYB. Phosphorylates Hsp90 and its co-chaperones
CC FKBP4 and CDC37, which is essential for chaperone function.
CC Regulates Wnt signaling by phosphorylating CTNNB1 and the
CC transcription factor LEF1. Acts as an ectokinase that
CC phosphorylates several extracellular proteins. During viral
CC infection, phosphorylates various proteins involved in the viral
CC life cycles of EBV, HSV, HBV, HCV, HIV, CMV and HPV.
CC -!- CATALYTIC ACTIVITY: ATP + a protein = ADP + a phosphoprotein.
CC -!- ENZYME REGULATION: Constitutively active protein kinase whose
CC activity is not directly affected by phosphorylation. Seems to be
CC regulated by level of expression and localization (By similarity).
CC -!- SUBUNIT: Heterotetramer composed of two catalytic subunits (alpha
CC chain and/or alpha' chain) and two regulatory subunits (beta
CC chains). The tetramer can exist as a combination of 2 alpha/2
CC beta, 2 alpha'/2 beta or 1 alpha/1 alpha'/2 beta subunits. Also
CC part of a CK2-SPT16-SSRP1 complex composed of SSRP1, SUPT16H,
CC CSNK2A1, CSNK2A2 and CSNK2B, which forms following UV irradiation.
CC Interacts with RNPS1.
CC -!- INTERACTION:
CC P68400:CSNK2A1; NbExp=3; IntAct=EBI-347451, EBI-347804;
CC P67870:CSNK2B; NbExp=6; IntAct=EBI-347451, EBI-348169;
CC O60282:KIF5C; NbExp=4; IntAct=EBI-347451, EBI-717170;
CC -!- MISCELLANEOUS: Can use both ATP and GTP as phosphoryl donors.
CC Phosphorylation by casein kinase 2 has been estimated to represent
CC up to one quarter of the eukaryotic phosphoproteome.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. Ser/Thr
CC protein kinase family. CK2 subfamily.
CC -!- SIMILARITY: Contains 1 protein kinase domain.
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DR EMBL; M55268; AAA51548.1; -; mRNA.
DR EMBL; BC008812; AAH08812.1; -; mRNA.
DR PIR; B35838; B35838.
DR RefSeq; NP_001887.1; NM_001896.2.
DR UniGene; Hs.82201; -.
DR PDB; 3E3B; X-ray; 3.20 A; X=1-334.
DR PDB; 3OFM; X-ray; 2.00 A; A=1-350.
DR PDB; 3U87; X-ray; 2.90 A; A/B=331-350.
DR PDBsum; 3E3B; -.
DR PDBsum; 3OFM; -.
DR PDBsum; 3U87; -.
DR ProteinModelPortal; P19784; -.
DR SMR; P19784; 8-332.
DR DIP; DIP-318N; -.
DR IntAct; P19784; 92.
DR MINT; MINT-5004107; -.
DR STRING; 9606.ENSP00000262506; -.
DR BindingDB; P19784; -.
DR ChEMBL; CHEMBL4070; -.
DR GuidetoPHARMACOLOGY; 1550; -.
DR PhosphoSite; P19784; -.
DR DMDM; 125266; -.
DR SWISS-2DPAGE; P19784; -.
DR PaxDb; P19784; -.
DR PeptideAtlas; P19784; -.
DR PRIDE; P19784; -.
DR DNASU; 1459; -.
DR Ensembl; ENST00000262506; ENSP00000262506; ENSG00000070770.
DR GeneID; 1459; -.
DR KEGG; hsa:1459; -.
DR UCSC; uc002enc.3; human.
DR CTD; 1459; -.
DR GeneCards; GC16M058191; -.
DR HGNC; HGNC:2459; CSNK2A2.
DR MIM; 115442; gene.
DR neXtProt; NX_P19784; -.
DR PharmGKB; PA26959; -.
DR eggNOG; COG0515; -.
DR HOGENOM; HOG000233021; -.
DR HOVERGEN; HBG107282; -.
DR InParanoid; P19784; -.
DR KO; K03097; -.
DR OMA; PSWGNQD; -.
DR OrthoDB; EOG7QG446; -.
DR PhylomeDB; P19784; -.
DR BRENDA; 2.7.11.1; 2681.
DR Reactome; REACT_111045; Developmental Biology.
DR Reactome; REACT_115566; Cell Cycle.
DR Reactome; REACT_21300; Mitotic M-M/G1 phases.
DR SignaLink; P19784; -.
DR ChiTaRS; CSNK2A2; human.
DR EvolutionaryTrace; P19784; -.
DR GeneWiki; CSNK2A2; -.
DR GenomeRNAi; 1459; -.
DR NextBio; 5997; -.
DR PRO; PR:P19784; -.
DR ArrayExpress; P19784; -.
DR Bgee; P19784; -.
DR CleanEx; HS_CSNK2A2; -.
DR Genevestigator; P19784; -.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0004674; F:protein serine/threonine kinase activity; IEA:UniProtKB-KW.
DR GO; GO:0006915; P:apoptotic process; IEA:UniProtKB-KW.
DR GO; GO:0007411; P:axon guidance; TAS:Reactome.
DR GO; GO:0000278; P:mitotic cell cycle; TAS:Reactome.
DR GO; GO:0071174; P:mitotic spindle checkpoint; IMP:UniProtKB.
DR GO; GO:0006355; P:regulation of transcription, DNA-dependent; IEA:UniProtKB-KW.
DR GO; GO:0006351; P:transcription, DNA-dependent; IEA:UniProtKB-KW.
DR GO; GO:0016055; P:Wnt receptor signaling pathway; IEA:UniProtKB-KW.
DR InterPro; IPR011009; Kinase-like_dom.
DR InterPro; IPR000719; Prot_kinase_dom.
DR InterPro; IPR017441; Protein_kinase_ATP_BS.
DR InterPro; IPR002290; Ser/Thr_dual-sp_kinase_dom.
DR InterPro; IPR008271; Ser/Thr_kinase_AS.
DR Pfam; PF00069; Pkinase; 1.
DR SMART; SM00220; S_TKc; 1.
DR SUPFAM; SSF56112; SSF56112; 1.
DR PROSITE; PS00107; PROTEIN_KINASE_ATP; 1.
DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 1.
DR PROSITE; PS00108; PROTEIN_KINASE_ST; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Apoptosis; ATP-binding; Cell cycle;
KW Complete proteome; Kinase; Nucleotide-binding; Phosphoprotein;
KW Polymorphism; Reference proteome; Serine/threonine-protein kinase;
KW Transcription; Transcription regulation; Transferase;
KW Wnt signaling pathway.
FT CHAIN 1 350 Casein kinase II subunit alpha'.
FT /FTId=PRO_0000085891.
FT DOMAIN 40 325 Protein kinase.
FT NP_BIND 46 54 ATP (By similarity).
FT ACT_SITE 157 157 Proton acceptor (By similarity).
FT BINDING 69 69 ATP (By similarity).
FT MOD_RES 13 13 Phosphotyrosine.
FT MOD_RES 18 18 Phosphoserine.
FT MOD_RES 21 21 Phosphoserine.
FT MOD_RES 97 97 N6-acetyllysine.
FT MOD_RES 288 288 Phosphoserine.
FT VARIANT 188 188 E -> A (in dbSNP:rs55911801).
FT /FTId=VAR_040416.
FT STRAND 11 13
FT TURN 14 16
FT HELIX 17 19
FT HELIX 22 25
FT HELIX 27 29
FT HELIX 37 39
FT STRAND 40 48
FT STRAND 50 59
FT TURN 60 63
FT STRAND 64 71
FT HELIX 76 88
FT TURN 89 91
FT STRAND 98 103
FT TURN 105 107
FT STRAND 110 115
FT HELIX 122 125
FT HELIX 131 150
FT HELIX 160 162
FT STRAND 163 166
FT TURN 167 170
FT STRAND 171 174
FT HELIX 196 198
FT HELIX 201 204
FT HELIX 213 228
FT STRAND 231 234
FT HELIX 239 250
FT HELIX 252 261
FT HELIX 270 273
FT HELIX 282 285
FT TURN 288 290
FT HELIX 291 293
FT HELIX 296 305
FT TURN 310 312
FT HELIX 316 320
FT HELIX 323 325
FT HELIX 326 331
SQ SEQUENCE 350 AA; 41213 MW; 3ECB92F6BD3DD7F1 CRC64;
MPGPAAGSRA RVYAEVNSLR SREYWDYEAH VPSWGNQDDY QLVRKLGRGK YSEVFEAINI
TNNERVVVKI LKPVKKKKIK REVKILENLR GGTNIIKLID TVKDPVSKTP ALVFEYINNT
DFKQLYQILT DFDIRFYMYE LLKALDYCHS KGIMHRDVKP HNVMIDHQQK KLRLIDWGLA
EFYHPAQEYN VRVASRYFKG PELLVDYQMY DYSLDMWSLG CMLASMIFRR EPFFHGQDNY
DQLVRIAKVL GTEELYGYLK KYHIDLDPHF NDILGQHSRK RWENFIHSEN RHLVSPEALD
LLDKLLRYDH QQRLTAKEAM EHPYFYPVVK EQSQPCADNA VLSSGLTAAR
//
ID CSK22_HUMAN Reviewed; 350 AA.
AC P19784;
DT 01-FEB-1991, integrated into UniProtKB/Swiss-Prot.
read moreDT 01-FEB-1991, sequence version 1.
DT 22-JAN-2014, entry version 147.
DE RecName: Full=Casein kinase II subunit alpha';
DE Short=CK II alpha';
DE EC=2.7.11.1;
GN Name=CSNK2A2; Synonyms=CK2A2;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=2174700; DOI=10.1021/bi00488a034;
RA Lozeman F.J., Litchfield D.W., Piening C., Takio K., Walsh K.A.,
RA Krebs E.G.;
RT "Isolation and characterization of human cDNA clones encoding the
RT alpha and the alpha' subunits of casein kinase II.";
RL Biochemistry 29:8436-8447(1990).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Ovary;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [3]
RP FUNCTION, AND INTERACTION WITH SSRP1 AND SUPT16H.
RX PubMed=11239457; DOI=10.1016/S1097-2765(01)00176-9;
RA Keller D.M., Zeng X., Wang Y., Zhang Q.H., Kapoor M., Shu H.,
RA Goodman R., Lozano G., Zhao Y., Lu H.;
RT "A DNA damage-induced p53 serine 392 kinase complex contains CK2,
RT hSpt16, and SSRP1.";
RL Mol. Cell 7:283-292(2001).
RN [4]
RP FUNCTION IN CELL CYCLE.
RX PubMed=11704824; DOI=10.1038/sj.onc.1204894;
RA Sayed M., Pelech S., Wong C., Marotta A., Salh B.;
RT "Protein kinase CK2 is involved in G2 arrest and apoptosis following
RT spindle damage in epithelial cells.";
RL Oncogene 20:6994-7005(2001).
RN [5]
RP INTERACTION WITH SSRP1 AND SUPT16H.
RX PubMed=12393879; DOI=10.1074/jbc.M209820200;
RA Keller D.M., Lu H.;
RT "p53 serine 392 phosphorylation increases after UV through induction
RT of the assembly of the CK2.hSPT16.SSRP1 complex.";
RL J. Biol. Chem. 277:50206-50213(2002).
RN [6]
RP FUNCTION IN APOPTOSIS.
RX PubMed=16193064; DOI=10.1038/sj.emboj.7600827;
RA Shin S., Lee Y., Kim W., Ko H., Choi H., Kim K.;
RT "Caspase-2 primes cancer cells for TRAIL-mediated apoptosis by
RT processing procaspase-8.";
RL EMBO J. 24:3532-3542(2005).
RN [7]
RP REVIEW ON FUNCTION.
RX PubMed=12631575; DOI=10.1096/fj.02-0473rev;
RA Meggio F., Pinna L.A.;
RT "One-thousand-and-one substrates of protein kinase CK2?";
RL FASEB J. 17:349-368(2003).
RN [8]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-18; SER-21 AND SER-288,
RP AND MASS SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=18691976; DOI=10.1016/j.molcel.2008.07.007;
RA Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R.,
RA Greff Z., Keri G., Stemmann O., Mann M.;
RT "Kinase-selective enrichment enables quantitative phosphoproteomics of
RT the kinome across the cell cycle.";
RL Mol. Cell 31:438-448(2008).
RN [9]
RP REVIEW ON STRUCTURE.
RX PubMed=19387553; DOI=10.1007/s00018-009-9149-8;
RA Niefind K., Raaf J., Issinger O.G.;
RT "Protein kinase CK2 in health and disease: Protein kinase CK2: from
RT structures to insights.";
RL Cell. Mol. Life Sci. 66:1800-1816(2009).
RN [10]
RP REVIEW ON FUNCTION.
RX PubMed=19387552; DOI=10.1007/s00018-009-9150-2;
RA St-Denis N.A., Litchfield D.W.;
RT "Protein kinase CK2 in health and disease: From birth to death: the
RT role of protein kinase CK2 in the regulation of cell proliferation and
RT survival.";
RL Cell. Mol. Life Sci. 66:1817-1829(2009).
RN [11]
RP REVIEW ON FUNCTION.
RX PubMed=19387551; DOI=10.1007/s00018-009-9151-1;
RA Filhol O., Cochet C.;
RT "Protein kinase CK2 in health and disease: Cellular functions of
RT protein kinase CK2: a dynamic affair.";
RL Cell. Mol. Life Sci. 66:1830-1839(2009).
RN [12]
RP REVIEW ON FUNCTION IN REGULATION OF HSP90.
RX PubMed=19387550; DOI=10.1007/s00018-009-9152-0;
RA Miyata Y.;
RT "Protein kinase CK2 in health and disease: CK2: the kinase controlling
RT the Hsp90 chaperone machinery.";
RL Cell. Mol. Life Sci. 66:1840-1849(2009).
RN [13]
RP REVIEW ON FUNCTION IN WNT SIGNALING.
RX PubMed=19387549; DOI=10.1007/s00018-009-9153-z;
RA Dominguez I., Sonenshein G.E., Seldin D.C.;
RT "Protein kinase CK2 in health and disease: CK2 and its role in Wnt and
RT NF-kappaB signaling: linking development and cancer.";
RL Cell. Mol. Life Sci. 66:1850-1857(2009).
RN [14]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-13; SER-18; SER-21 AND
RP SER-288, AND MASS SPECTROMETRY.
RX PubMed=19369195; DOI=10.1074/mcp.M800588-MCP200;
RA Oppermann F.S., Gnad F., Olsen J.V., Hornberger R., Greff Z., Keri G.,
RA Mann M., Daub H.;
RT "Large-scale proteomics analysis of the human kinome.";
RL Mol. Cell. Proteomics 8:1751-1764(2009).
RN [15]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-97, AND MASS SPECTROMETRY.
RX PubMed=19608861; DOI=10.1126/science.1175371;
RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M.,
RA Walther T.C., Olsen J.V., Mann M.;
RT "Lysine acetylation targets protein complexes and co-regulates major
RT cellular functions.";
RL Science 325:834-840(2009).
RN [16]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P.,
RA Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [17]
RP X-RAY CRYSTALLOGRAPHY (3.20 ANGSTROMS) OF 1-334 IN COMPLEX WITH
RP INHIBITOR.
RX PubMed=19193990; DOI=10.1107/S1744309108043194;
RA Nakaniwa T., Kinoshita T., Sekiguchi Y., Tada T., Nakanishi I.,
RA Kitaura K., Suzuki Y., Ohno H., Hirasawa A., Tsujimoto G.;
RT "Structure of human protein kinase CK2 alpha 2 with a potent indazole-
RT derivative inhibitor.";
RL Acta Crystallogr. F 65:75-79(2009).
RN [18]
RP X-RAY CRYSTALLOGRAPHY (2.00 ANGSTROMS).
RX PubMed=21241709; DOI=10.1016/j.jmb.2011.01.020;
RA Bischoff N., Olsen B., Raaf J., Bretner M., Issinger O.G., Niefind K.;
RT "Structure of the human protein kinase CK2 catalytic subunit CK2alpha'
RT and interaction thermodynamics with the regulatory subunit CK2beta.";
RL J. Mol. Biol. 407:1-12(2011).
RN [19]
RP VARIANT [LARGE SCALE ANALYSIS] ALA-188.
RX PubMed=17344846; DOI=10.1038/nature05610;
RA Greenman C., Stephens P., Smith R., Dalgliesh G.L., Hunter C.,
RA Bignell G., Davies H., Teague J., Butler A., Stevens C., Edkins S.,
RA O'Meara S., Vastrik I., Schmidt E.E., Avis T., Barthorpe S.,
RA Bhamra G., Buck G., Choudhury B., Clements J., Cole J., Dicks E.,
RA Forbes S., Gray K., Halliday K., Harrison R., Hills K., Hinton J.,
RA Jenkinson A., Jones D., Menzies A., Mironenko T., Perry J., Raine K.,
RA Richardson D., Shepherd R., Small A., Tofts C., Varian J., Webb T.,
RA West S., Widaa S., Yates A., Cahill D.P., Louis D.N., Goldstraw P.,
RA Nicholson A.G., Brasseur F., Looijenga L., Weber B.L., Chiew Y.-E.,
RA DeFazio A., Greaves M.F., Green A.R., Campbell P., Birney E.,
RA Easton D.F., Chenevix-Trench G., Tan M.-H., Khoo S.K., Teh B.T.,
RA Yuen S.T., Leung S.Y., Wooster R., Futreal P.A., Stratton M.R.;
RT "Patterns of somatic mutation in human cancer genomes.";
RL Nature 446:153-158(2007).
CC -!- FUNCTION: Catalytic subunit of a constitutively active
CC serine/threonine-protein kinase complex that phosphorylates a
CC large number of substrates containing acidic residues C-terminal
CC to the phosphorylated serine or threonine. Regulates numerous
CC cellular processes, such as cell cycle progression, apoptosis and
CC transcription, as well as viral infection. May act as a regulatory
CC node which integrates and coordinates numerous signals leading to
CC an appropriate cellular response. During mitosis, functions as a
CC component of the p53/TP53-dependent spindle assembly checkpoint
CC (SAC) that maintains cyclin-B-CDK1 activity and G2 arrest in
CC response to spindle damage. Also required for p53/TP53-mediated
CC apoptosis, phosphorylating 'Ser-392' of p53/TP53 following UV
CC irradiation. Can also negatively regulate apoptosis.
CC Phosphorylates the caspases CASP9 and CASP2 and the apoptotic
CC regulator NOL3. Phosphorylation protects CASP9 from cleavage and
CC activation by CASP8, and inhibits the dimerization of CASP2 and
CC activation of CASP8. Regulates transcription by direct
CC phosphorylation of RNA polymerases I, II, III and IV. Also
CC phosphorylates and regulates numerous transcription factors
CC including NF-kappa-B, STAT1, CREB1, IRF1, IRF2, ATF1, SRF, MAX,
CC JUN, FOS, MYC and MYB. Phosphorylates Hsp90 and its co-chaperones
CC FKBP4 and CDC37, which is essential for chaperone function.
CC Regulates Wnt signaling by phosphorylating CTNNB1 and the
CC transcription factor LEF1. Acts as an ectokinase that
CC phosphorylates several extracellular proteins. During viral
CC infection, phosphorylates various proteins involved in the viral
CC life cycles of EBV, HSV, HBV, HCV, HIV, CMV and HPV.
CC -!- CATALYTIC ACTIVITY: ATP + a protein = ADP + a phosphoprotein.
CC -!- ENZYME REGULATION: Constitutively active protein kinase whose
CC activity is not directly affected by phosphorylation. Seems to be
CC regulated by level of expression and localization (By similarity).
CC -!- SUBUNIT: Heterotetramer composed of two catalytic subunits (alpha
CC chain and/or alpha' chain) and two regulatory subunits (beta
CC chains). The tetramer can exist as a combination of 2 alpha/2
CC beta, 2 alpha'/2 beta or 1 alpha/1 alpha'/2 beta subunits. Also
CC part of a CK2-SPT16-SSRP1 complex composed of SSRP1, SUPT16H,
CC CSNK2A1, CSNK2A2 and CSNK2B, which forms following UV irradiation.
CC Interacts with RNPS1.
CC -!- INTERACTION:
CC P68400:CSNK2A1; NbExp=3; IntAct=EBI-347451, EBI-347804;
CC P67870:CSNK2B; NbExp=6; IntAct=EBI-347451, EBI-348169;
CC O60282:KIF5C; NbExp=4; IntAct=EBI-347451, EBI-717170;
CC -!- MISCELLANEOUS: Can use both ATP and GTP as phosphoryl donors.
CC Phosphorylation by casein kinase 2 has been estimated to represent
CC up to one quarter of the eukaryotic phosphoproteome.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. Ser/Thr
CC protein kinase family. CK2 subfamily.
CC -!- SIMILARITY: Contains 1 protein kinase domain.
CC -----------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution-NoDerivs License
CC -----------------------------------------------------------------------
DR EMBL; M55268; AAA51548.1; -; mRNA.
DR EMBL; BC008812; AAH08812.1; -; mRNA.
DR PIR; B35838; B35838.
DR RefSeq; NP_001887.1; NM_001896.2.
DR UniGene; Hs.82201; -.
DR PDB; 3E3B; X-ray; 3.20 A; X=1-334.
DR PDB; 3OFM; X-ray; 2.00 A; A=1-350.
DR PDB; 3U87; X-ray; 2.90 A; A/B=331-350.
DR PDBsum; 3E3B; -.
DR PDBsum; 3OFM; -.
DR PDBsum; 3U87; -.
DR ProteinModelPortal; P19784; -.
DR SMR; P19784; 8-332.
DR DIP; DIP-318N; -.
DR IntAct; P19784; 92.
DR MINT; MINT-5004107; -.
DR STRING; 9606.ENSP00000262506; -.
DR BindingDB; P19784; -.
DR ChEMBL; CHEMBL4070; -.
DR GuidetoPHARMACOLOGY; 1550; -.
DR PhosphoSite; P19784; -.
DR DMDM; 125266; -.
DR SWISS-2DPAGE; P19784; -.
DR PaxDb; P19784; -.
DR PeptideAtlas; P19784; -.
DR PRIDE; P19784; -.
DR DNASU; 1459; -.
DR Ensembl; ENST00000262506; ENSP00000262506; ENSG00000070770.
DR GeneID; 1459; -.
DR KEGG; hsa:1459; -.
DR UCSC; uc002enc.3; human.
DR CTD; 1459; -.
DR GeneCards; GC16M058191; -.
DR HGNC; HGNC:2459; CSNK2A2.
DR MIM; 115442; gene.
DR neXtProt; NX_P19784; -.
DR PharmGKB; PA26959; -.
DR eggNOG; COG0515; -.
DR HOGENOM; HOG000233021; -.
DR HOVERGEN; HBG107282; -.
DR InParanoid; P19784; -.
DR KO; K03097; -.
DR OMA; PSWGNQD; -.
DR OrthoDB; EOG7QG446; -.
DR PhylomeDB; P19784; -.
DR BRENDA; 2.7.11.1; 2681.
DR Reactome; REACT_111045; Developmental Biology.
DR Reactome; REACT_115566; Cell Cycle.
DR Reactome; REACT_21300; Mitotic M-M/G1 phases.
DR SignaLink; P19784; -.
DR ChiTaRS; CSNK2A2; human.
DR EvolutionaryTrace; P19784; -.
DR GeneWiki; CSNK2A2; -.
DR GenomeRNAi; 1459; -.
DR NextBio; 5997; -.
DR PRO; PR:P19784; -.
DR ArrayExpress; P19784; -.
DR Bgee; P19784; -.
DR CleanEx; HS_CSNK2A2; -.
DR Genevestigator; P19784; -.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0004674; F:protein serine/threonine kinase activity; IEA:UniProtKB-KW.
DR GO; GO:0006915; P:apoptotic process; IEA:UniProtKB-KW.
DR GO; GO:0007411; P:axon guidance; TAS:Reactome.
DR GO; GO:0000278; P:mitotic cell cycle; TAS:Reactome.
DR GO; GO:0071174; P:mitotic spindle checkpoint; IMP:UniProtKB.
DR GO; GO:0006355; P:regulation of transcription, DNA-dependent; IEA:UniProtKB-KW.
DR GO; GO:0006351; P:transcription, DNA-dependent; IEA:UniProtKB-KW.
DR GO; GO:0016055; P:Wnt receptor signaling pathway; IEA:UniProtKB-KW.
DR InterPro; IPR011009; Kinase-like_dom.
DR InterPro; IPR000719; Prot_kinase_dom.
DR InterPro; IPR017441; Protein_kinase_ATP_BS.
DR InterPro; IPR002290; Ser/Thr_dual-sp_kinase_dom.
DR InterPro; IPR008271; Ser/Thr_kinase_AS.
DR Pfam; PF00069; Pkinase; 1.
DR SMART; SM00220; S_TKc; 1.
DR SUPFAM; SSF56112; SSF56112; 1.
DR PROSITE; PS00107; PROTEIN_KINASE_ATP; 1.
DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 1.
DR PROSITE; PS00108; PROTEIN_KINASE_ST; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Apoptosis; ATP-binding; Cell cycle;
KW Complete proteome; Kinase; Nucleotide-binding; Phosphoprotein;
KW Polymorphism; Reference proteome; Serine/threonine-protein kinase;
KW Transcription; Transcription regulation; Transferase;
KW Wnt signaling pathway.
FT CHAIN 1 350 Casein kinase II subunit alpha'.
FT /FTId=PRO_0000085891.
FT DOMAIN 40 325 Protein kinase.
FT NP_BIND 46 54 ATP (By similarity).
FT ACT_SITE 157 157 Proton acceptor (By similarity).
FT BINDING 69 69 ATP (By similarity).
FT MOD_RES 13 13 Phosphotyrosine.
FT MOD_RES 18 18 Phosphoserine.
FT MOD_RES 21 21 Phosphoserine.
FT MOD_RES 97 97 N6-acetyllysine.
FT MOD_RES 288 288 Phosphoserine.
FT VARIANT 188 188 E -> A (in dbSNP:rs55911801).
FT /FTId=VAR_040416.
FT STRAND 11 13
FT TURN 14 16
FT HELIX 17 19
FT HELIX 22 25
FT HELIX 27 29
FT HELIX 37 39
FT STRAND 40 48
FT STRAND 50 59
FT TURN 60 63
FT STRAND 64 71
FT HELIX 76 88
FT TURN 89 91
FT STRAND 98 103
FT TURN 105 107
FT STRAND 110 115
FT HELIX 122 125
FT HELIX 131 150
FT HELIX 160 162
FT STRAND 163 166
FT TURN 167 170
FT STRAND 171 174
FT HELIX 196 198
FT HELIX 201 204
FT HELIX 213 228
FT STRAND 231 234
FT HELIX 239 250
FT HELIX 252 261
FT HELIX 270 273
FT HELIX 282 285
FT TURN 288 290
FT HELIX 291 293
FT HELIX 296 305
FT TURN 310 312
FT HELIX 316 320
FT HELIX 323 325
FT HELIX 326 331
SQ SEQUENCE 350 AA; 41213 MW; 3ECB92F6BD3DD7F1 CRC64;
MPGPAAGSRA RVYAEVNSLR SREYWDYEAH VPSWGNQDDY QLVRKLGRGK YSEVFEAINI
TNNERVVVKI LKPVKKKKIK REVKILENLR GGTNIIKLID TVKDPVSKTP ALVFEYINNT
DFKQLYQILT DFDIRFYMYE LLKALDYCHS KGIMHRDVKP HNVMIDHQQK KLRLIDWGLA
EFYHPAQEYN VRVASRYFKG PELLVDYQMY DYSLDMWSLG CMLASMIFRR EPFFHGQDNY
DQLVRIAKVL GTEELYGYLK KYHIDLDPHF NDILGQHSRK RWENFIHSEN RHLVSPEALD
LLDKLLRYDH QQRLTAKEAM EHPYFYPVVK EQSQPCADNA VLSSGLTAAR
//
MIM
115442
*RECORD*
*FIELD* NO
115442
*FIELD* TI
*115442 CASEIN KINASE II, ALPHA-2; CSNK2A2
;;CASEIN KINASE II, ALPHA-PRIME SUBUNIT; CK2A2
read more*FIELD* TX
CLONING
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.
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.
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.
MAPPING
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.)
ANIMAL MODEL
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.
*FIELD* RF
1. 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.
2. 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.
3. 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.
4. 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.
5. 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.
6. 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.
7. 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.
8. 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.
*FIELD* CN
Patricia A. Hartz - updated: 5/28/2008
Ada Hamosh - updated: 11/25/2002
Ada Hamosh - updated: 10/23/2002
Stylianos E. Antonarakis - updated: 3/12/2001
Victor A. McKusick - updated: 8/30/1999
*FIELD* CD
Victor A. McKusick: 10/26/1990
*FIELD* ED
wwang: 10/14/2008
mgross: 6/3/2008
terry: 5/28/2008
mgross: 9/18/2003
alopez: 12/19/2002
alopez: 11/25/2002
terry: 11/25/2002
alopez: 10/23/2002
mgross: 3/12/2001
psherman: 10/22/1999
alopez: 8/30/1999
terry: 8/30/1999
mgross: 3/16/1999
mark: 1/19/1998
mark: 10/18/1996
carol: 2/8/1994
carol: 3/25/1992
supermim: 3/16/1992
carol: 1/2/1991
carol: 10/26/1990
*RECORD*
*FIELD* NO
115442
*FIELD* TI
*115442 CASEIN KINASE II, ALPHA-2; CSNK2A2
;;CASEIN KINASE II, ALPHA-PRIME SUBUNIT; CK2A2
read more*FIELD* TX
CLONING
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.
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.
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.
MAPPING
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.)
ANIMAL MODEL
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.
*FIELD* RF
1. 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.
2. 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.
3. 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.
4. 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.
5. 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.
6. 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.
7. 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,
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8. Yang-Feng, T. L.; Zheng, K.; Kopatz, I.; Naiman, T.; Canaani, D.
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*FIELD* CN
Patricia A. Hartz - updated: 5/28/2008
Ada Hamosh - updated: 11/25/2002
Ada Hamosh - updated: 10/23/2002
Stylianos E. Antonarakis - updated: 3/12/2001
Victor A. McKusick - updated: 8/30/1999
*FIELD* CD
Victor A. McKusick: 10/26/1990
*FIELD* ED
wwang: 10/14/2008
mgross: 6/3/2008
terry: 5/28/2008
mgross: 9/18/2003
alopez: 12/19/2002
alopez: 11/25/2002
terry: 11/25/2002
alopez: 10/23/2002
mgross: 3/12/2001
psherman: 10/22/1999
alopez: 8/30/1999
terry: 8/30/1999
mgross: 3/16/1999
mark: 1/19/1998
mark: 10/18/1996
carol: 2/8/1994
carol: 3/25/1992
supermim: 3/16/1992
carol: 1/2/1991
carol: 10/26/1990