CSK22_MOUSE
ID CSK22_MOUSE Reviewed; 350 AA.
AC O54833;
DT 01-DEC-2000, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-1998, sequence version 1.
DT 03-AUG-2022, entry version 195.
DE RecName: Full=Casein kinase II subunit alpha';
DE Short=CK II alpha';
DE EC=2.7.11.1;
GN Name=Csnk2a2;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=C57BL/6J;
RX PubMed=9503019; DOI=10.1006/geno.1997.5154;
RA Xu X., Rich E.S. Jr., Seldin D.C.;
RT "Murine protein kinase CK2 alpha': cDNA and genomic cloning and chromosomal
RT mapping.";
RL Genomics 48:79-86(1998).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=C57BL/6J;
RX PubMed=9694889; DOI=10.1074/jbc.273.33.21291;
RA Orlandini M., Semplici F., Ferruzzi R., Meggio F., Pinna L.A., Oliviero S.;
RT "Protein kinase CK2alpha' is induced by serum as a delayed early gene and
RT cooperates with Ha-ras in fibroblast transformation.";
RL J. Biol. Chem. 273:21291-21297(1998).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=129; TISSUE=Mammary gland;
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 project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [4]
RP DISRUPTION PHENOTYPE, AND TISSUE SPECIFICITY.
RX PubMed=10471512; DOI=10.1038/12729;
RA Xu X., Toselli P.A., Russell L.D., Seldin D.C.;
RT "Globozoospermia in mice lacking the casein kinase II alpha' catalytic
RT subunit.";
RL Nat. Genet. 23:118-121(1999).
RN [5]
RP INTERACTION WITH CSNKA2IP.
RX PubMed=19273531; DOI=10.1093/nar/gkp094;
RA Bai X., Silvius D., Chan E.D., Escalier D., Xu S.X.;
RT "Identification and characterization of a novel testis-specific gene CKT2,
RT which encodes a substrate for protein kinase CK2.";
RL Nucleic Acids Res. 37:2699-2711(2009).
RN [6]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Spleen, and Testis;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [7]
RP SUBCELLULAR LOCATION, AND INTERACTION WITH SIRT6.
RX PubMed=28355567; DOI=10.1016/j.celrep.2017.03.006;
RA Chen Q., Hao W., Xiao C., Wang R., Xu X., Lu H., Chen W., Deng C.X.;
RT "SIRT6 is essential for adipocyte differentiation by regulating mitotic
RT clonal expansion.";
RL Cell Rep. 18:3155-3166(2017).
CC -!- FUNCTION: Catalytic subunit of a constitutively active
CC serine/threonine-protein kinase complex that phosphorylates a large
CC number of substrates containing acidic residues C-terminal to the
CC phosphorylated serine or threonine. Regulates numerous cellular
CC processes, such as cell cycle progression, apoptosis and transcription,
CC as well as viral infection. May act as a regulatory node which
CC integrates and coordinates numerous signals leading to an appropriate
CC cellular response. During mitosis, functions as a component of the
CC p53/TP53-dependent spindle assembly checkpoint (SAC) that maintains
CC cyclin-B-CDK1 activity and G2 arrest in response to spindle damage.
CC Also required for p53/TP53-mediated apoptosis, phosphorylating 'Ser-
CC 392' of p53/TP53 following UV irradiation. Can also negatively regulate
CC apoptosis. Phosphorylates the caspases CASP9 and CASP2 and the
CC apoptotic regulator NOL3. Phosphorylation protects CASP9 from cleavage
CC and activation by CASP8, and inhibits the dimerization of CASP2 and
CC activation of CASP8. Regulates transcription by direct phosphorylation
CC of RNA polymerases I, II, III and IV. Also phosphorylates and regulates
CC numerous transcription factors including NF-kappa-B, STAT1, CREB1,
CC IRF1, IRF2, ATF1, SRF, MAX, JUN, FOS, MYC and MYB. Phosphorylates Hsp90
CC and its co-chaperones FKBP4 and CDC37, which is essential for chaperone
CC function. Regulates Wnt signaling by phosphorylating CTNNB1 and the
CC transcription factor LEF1. Acts as an ectokinase that phosphorylates
CC several extracellular proteins. {ECO:0000250|UniProtKB:P19784}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-seryl-[protein] = ADP + H(+) + O-phospho-L-seryl-
CC [protein]; Xref=Rhea:RHEA:17989, Rhea:RHEA-COMP:9863, Rhea:RHEA-
CC COMP:11604, ChEBI:CHEBI:15378, ChEBI:CHEBI:29999, ChEBI:CHEBI:30616,
CC ChEBI:CHEBI:83421, ChEBI:CHEBI:456216; EC=2.7.11.1;
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-threonyl-[protein] = ADP + H(+) + O-phospho-L-
CC threonyl-[protein]; Xref=Rhea:RHEA:46608, Rhea:RHEA-COMP:11060,
CC Rhea:RHEA-COMP:11605, ChEBI:CHEBI:15378, ChEBI:CHEBI:30013,
CC ChEBI:CHEBI:30616, ChEBI:CHEBI:61977, ChEBI:CHEBI:456216;
CC EC=2.7.11.1;
CC -!- ACTIVITY 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 {ECO:0000250|UniProtKB:P19784}.
CC -!- SUBUNIT: Heterotetramer composed of two catalytic subunits (alpha chain
CC and/or alpha' chain) and two regulatory subunits (beta chains). The
CC tetramer can exist as a combination of 2 alpha/2 beta, 2 alpha'/2 beta
CC or 1 alpha/1 alpha'/2 beta subunits. Also part of a CK2-SPT16-SSRP1
CC complex composed of SSRP1, SUPT16H, CSNK2A1, CSNK2A2 and CSNK2B, which
CC forms following UV irradiation. Interacts with RNPS1 (By similarity).
CC Interacts with CSNKA2IP (via C-terminus) (PubMed:19273531). Interacts
CC with SIRT6; preventing CSNK2A2 localization to the nucleus
CC (PubMed:28355567). {ECO:0000250|UniProtKB:P19784,
CC ECO:0000269|PubMed:19273531, ECO:0000269|PubMed:28355567}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:28355567}. Cytoplasm
CC {ECO:0000269|PubMed:28355567}. Note=Interaction with SIRT6 prevents
CC translocation into the nucleus. {ECO:0000269|PubMed:28355567}.
CC -!- TISSUE SPECIFICITY: Highly expressed in brain, testis and mature
CC epididymal spermatozoa. Weakly expressed in kidney, liver, lung, spleen
CC and thymus (at protein level). {ECO:0000269|PubMed:10471512}.
CC -!- DISRUPTION PHENOTYPE: Infertile male mice with oligospermia and
CC globozoospermia. {ECO:0000269|PubMed:10471512}.
CC -!- MISCELLANEOUS: Can use both ATP and GTP as phosphoryl donors.
CC Phosphorylation by casein kinase 2 has been estimated to represent up
CC to one quarter of the eukaryotic phosphoproteome.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. Ser/Thr protein
CC kinase family. CK2 subfamily. {ECO:0000255|PROSITE-ProRule:PRU00159}.
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DR EMBL; AF012251; AAC53552.1; -; mRNA.
DR EMBL; AJ001420; CAA04753.1; -; mRNA.
DR EMBL; BC057862; AAH57862.1; -; mRNA.
DR CCDS; CCDS22562.1; -.
DR RefSeq; NP_034104.1; NM_009974.3.
DR AlphaFoldDB; O54833; -.
DR SMR; O54833; -.
DR BioGRID; 198946; 38.
DR CORUM; O54833; -.
DR IntAct; O54833; 7.
DR MINT; O54833; -.
DR STRING; 10090.ENSMUSP00000055919; -.
DR ChEMBL; CHEMBL5326; -.
DR iPTMnet; O54833; -.
DR PhosphoSitePlus; O54833; -.
DR EPD; O54833; -.
DR jPOST; O54833; -.
DR PaxDb; O54833; -.
DR PeptideAtlas; O54833; -.
DR PRIDE; O54833; -.
DR ProteomicsDB; 284034; -.
DR Antibodypedia; 15225; 333 antibodies from 34 providers.
DR DNASU; 13000; -.
DR Ensembl; ENSMUST00000056919; ENSMUSP00000055919; ENSMUSG00000046707.
DR Ensembl; ENSMUST00000212214; ENSMUSP00000148404; ENSMUSG00000046707.
DR GeneID; 13000; -.
DR KEGG; mmu:13000; -.
DR UCSC; uc009myk.2; mouse.
DR CTD; 1459; -.
DR MGI; MGI:88547; Csnk2a2.
DR VEuPathDB; HostDB:ENSMUSG00000046707; -.
DR eggNOG; KOG0668; Eukaryota.
DR GeneTree; ENSGT00390000004215; -.
DR HOGENOM; CLU_000288_70_4_1; -.
DR InParanoid; O54833; -.
DR OMA; YHPEKEY; -.
DR OrthoDB; 1098380at2759; -.
DR PhylomeDB; O54833; -.
DR TreeFam; TF300483; -.
DR BRENDA; 2.7.11.1; 3474.
DR Reactome; R-MMU-1483191; Synthesis of PC.
DR Reactome; R-MMU-201688; WNT mediated activation of DVL.
DR Reactome; R-MMU-2514853; Condensation of Prometaphase Chromosomes.
DR Reactome; R-MMU-445144; Signal transduction by L1.
DR Reactome; R-MMU-6804756; Regulation of TP53 Activity through Phosphorylation.
DR Reactome; R-MMU-6814122; Cooperation of PDCL (PhLP1) and TRiC/CCT in G-protein beta folding.
DR Reactome; R-MMU-8934903; Receptor Mediated Mitophagy.
DR Reactome; R-MMU-8939243; RUNX1 interacts with co-factors whose precise effect on RUNX1 targets is not known.
DR Reactome; R-MMU-8948751; Regulation of PTEN stability and activity.
DR BioGRID-ORCS; 13000; 6 hits in 75 CRISPR screens.
DR ChiTaRS; Csnk2a2; mouse.
DR PRO; PR:O54833; -.
DR Proteomes; UP000000589; Chromosome 8.
DR RNAct; O54833; protein.
DR Bgee; ENSMUSG00000046707; Expressed in rostral migratory stream and 288 other tissues.
DR ExpressionAtlas; O54833; baseline and differential.
DR Genevisible; O54833; MM.
DR GO; GO:0001669; C:acrosomal vesicle; ISO:MGI.
DR GO; GO:0000785; C:chromatin; ISO:MGI.
DR GO; GO:0005737; C:cytoplasm; ISO:MGI.
DR GO; GO:0005829; C:cytosol; IBA:GO_Central.
DR GO; GO:0005634; C:nucleus; ISO:MGI.
DR GO; GO:0031519; C:PcG protein complex; ISO:MGI.
DR GO; GO:0005886; C:plasma membrane; ISO:MGI.
DR GO; GO:0005956; C:protein kinase CK2 complex; IBA:GO_Central.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0004672; F:protein kinase activity; IDA:MGI.
DR GO; GO:0047485; F:protein N-terminus binding; ISO:MGI.
DR GO; GO:0106310; F:protein serine kinase activity; IEA:RHEA.
DR GO; GO:0004674; F:protein serine/threonine kinase activity; IDA:MGI.
DR GO; GO:0006915; P:apoptotic process; IEA:UniProtKB-KW.
DR GO; GO:0007049; P:cell cycle; IEA:UniProtKB-KW.
DR GO; GO:2000059; P:negative regulation of ubiquitin-dependent protein catabolic process; ISO:MGI.
DR GO; GO:0018105; P:peptidyl-serine phosphorylation; ISO:MGI.
DR GO; GO:0018107; P:peptidyl-threonine phosphorylation; IBA:GO_Central.
DR GO; GO:0006468; P:protein phosphorylation; IDA:MGI.
DR GO; GO:0051726; P:regulation of cell cycle; IDA:MGI.
DR GO; GO:1905818; P:regulation of chromosome separation; ISS:UniProtKB.
DR GO; GO:0016055; P:Wnt signaling pathway; IEA:UniProtKB-KW.
DR CDD; cd14132; STKc_CK2_alpha; 1.
DR InterPro; IPR045216; CK2_alpha.
DR InterPro; IPR011009; Kinase-like_dom_sf.
DR InterPro; IPR000719; Prot_kinase_dom.
DR InterPro; IPR017441; Protein_kinase_ATP_BS.
DR InterPro; IPR008271; Ser/Thr_kinase_AS.
DR PANTHER; PTHR24054; PTHR24054; 1.
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 Acetylation; Apoptosis; ATP-binding; Cell cycle; Cytoplasm; Kinase;
KW Nucleotide-binding; Nucleus; Phosphoprotein; Reference proteome;
KW Serine/threonine-protein kinase; Transcription; Transcription regulation;
KW Transferase; Wnt signaling pathway.
FT CHAIN 1..350
FT /note="Casein kinase II subunit alpha'"
FT /id="PRO_0000085892"
FT DOMAIN 40..325
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT ACT_SITE 157
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT ECO:0000255|PROSITE-ProRule:PRU10027"
FT BINDING 46..54
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 69
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT MOD_RES 13
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:P19784"
FT MOD_RES 18
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P19784"
FT MOD_RES 21
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P19784"
FT MOD_RES 97
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P19784"
FT MOD_RES 288
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P19784"
SQ SEQUENCE 350 AA; 41215 MW; C5FA314617627F5B CRC64;
MPGPAAGSRA RVYAEVNSLR SREYWDYEAH VPSWGNQDDY QLVRKLGRGK YSEVFEAINI
TNNERVVVKI LKPVKKKKIK REVKILENLR GGTNIIKLID TVKDPVSKTP ALVFEYINNT
DFKQLYQILT DFDIRFYMYE LLKALDYCHS KGIMHRDVKP HNVMIDHQQK KLRLIDWGLA
EFYHPAQEYN VRVASRYFKG PELLVDYQMY DYSLDMWSLG CMLASMIFRK EPFFHGQDNY
DQLVRIAKVL GTDELYGYLK KYHIDLDPHF NDILGQHSRK RWENFIHSEN RHLVSPEALD
LLDKLLRYDH QQRLTAKEAM EHPYFYPVVK EQSQPCAENT VLSSGLTAAR
