ID CSK21_BOVIN Reviewed; 391 AA.
AC P68399; P19138; P20426; Q14013; Q2KI05;
DT 23-NOV-2004, integrated into UniProtKB/Swiss-Prot.
DT 23-NOV-2004, sequence version 1.
DT 27-MAR-2024, entry version 133.
DE RecName: Full=Casein kinase II subunit alpha;
DE Short=CK II alpha;
DE EC=2.7.11.1 {ECO:0000250|UniProtKB:P68400};
GN Name=CSNK2A1; Synonyms=CK2A1;
OS Bos taurus (Bovine).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Artiodactyla; Ruminantia; Pecora; Bovidae;
OC Bovinae; Bos.
OX NCBI_TaxID=9913;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=8467809; DOI=10.1002/j.1460-2075.1993.tb05807.x;
RA Ole-Moiyoi O.K., Brown W.C., Iams K.P., Nayar A., Tsukamoto T.,
RA Macklin M.D.;
RT "Evidence for the induction of casein kinase II in bovine lymphocytes
RT transformed by the intracellular protozoan parasite Theileria parva.";
RL EMBO J. 12:1621-1631(1993).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Testis;
RA Watanabe M., Yuge M., Maeda O., Ohno S., Kawasaki H., Suzuki K., Hidaka H.;
RT "Nucleotide sequence of cDNA for casein kinase II alpha subunit from bovine
RT testis.";
RL Submitted (OCT-1990) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=Hereford; TISSUE=Heart ventricle;
RG NIH - Mammalian Gene Collection (MGC) project;
RL Submitted (JAN-2006) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP PROTEIN SEQUENCE OF 50-59; 103-122; 230-239; 248-279 AND 284-303.
RC TISSUE=Testis;
RX PubMed=2159007; DOI=10.1016/s0021-9258(19)39162-8;
RA Litchfield D.W., Lozeman F.J., Piening C., Sommercorn J., Takio K.,
RA Walsh K.A., Krebs E.G.;
RT "Subunit structure of casein kinase II from bovine testis. Demonstration
RT that the alpha and alpha' subunits are distinct polypeptides.";
RL J. Biol. Chem. 265:7638-7644(1990).
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. Phosphorylates a number of
CC DNA repair proteins in response to DNA damage, such as MDC1, RAD9A,
CC RAD51 and HTATSF1, promoting their recruitment to DNA damage sites. Can
CC also negatively regulate apoptosis. Phosphorylates the caspases CASP9
CC and CASP2 and the apoptotic regulator NOL3. Phosphorylation protects
CC CASP9 from cleavage and activation by CASP8, and inhibits the
CC dimerization of CASP2 and activation of CASP8. Phosphorylates YY1,
CC protecting YY1 from cleavage by CASP7 during apoptosis. Regulates
CC transcription by direct phosphorylation of RNA polymerases I, II, III
CC and IV. Also phosphorylates and regulates numerous transcription
CC factors including NF-kappa-B, STAT1, CREB1, IRF1, IRF2, ATF1, ATF4,
CC SRF, MAX, JUN, FOS, MYC and MYB. Phosphorylates Hsp90 and its co-
CC chaperones FKBP4 and CDC37, which is essential for chaperone function.
CC Mediates sequential phosphorylation of FNIP1, promoting its gradual
CC interaction with Hsp90, leading to activate both kinase and non-kinase
CC client proteins of Hsp90. Regulates Wnt signaling by phosphorylating
CC CTNNB1 and the transcription factor LEF1. Acts as an ectokinase that
CC phosphorylates several extracellular proteins. Plays an important role
CC in the circadian clock function by phosphorylating BMAL1 at 'Ser-90'
CC which is pivotal for its interaction with CLOCK and which controls
CC CLOCK nuclear entry (By similarity). Phosphorylates FMR1, promoting
CC FMR1-dependent formation of a membraneless compartment (By similarity).
CC {ECO:0000250|UniProtKB:P19139, ECO:0000250|UniProtKB:P68400}.
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 Evidence={ECO:0000250|UniProtKB:P68400};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:17990;
CC Evidence={ECO:0000250|UniProtKB:P68400};
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; Evidence={ECO:0000250|UniProtKB:P68400};
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}.
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, SNAI1, PML and
CC CCAR2 (By similarity). {ECO:0000250|UniProtKB:P68400}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000250|UniProtKB:P68400}.
CC -!- PTM: Phosphorylated at Thr-344, Thr-360, Ser-362 and Ser-370 by CDK1 in
CC prophase and metaphase and dephosphorylated during anaphase.
CC Phosphorylation does not directly affect casein kinase 2 activity, but
CC may contribute to its regulation by forming binding sites for
CC interacting proteins and/or targeting it to different compartments (By
CC similarity). {ECO:0000250}.
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}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; M93665; AAA18213.1; -; mRNA.
DR EMBL; X54962; CAA38710.1; -; mRNA.
DR EMBL; BC112816; AAI12817.1; -; mRNA.
DR PIR; S21335; S21335.
DR RefSeq; NP_777060.2; NM_174635.2.
DR AlphaFoldDB; P68399; -.
DR SMR; P68399; -.
DR BioGRID; 159676; 4.
DR CORUM; P68399; -.
DR STRING; 9913.ENSBTAP00000059962; -.
DR ChEMBL; CHEMBL3988628; -.
DR iPTMnet; P68399; -.
DR PaxDb; 9913-ENSBTAP00000050939; -.
DR Ensembl; ENSBTAT00000057062.3; ENSBTAP00000050939.3; ENSBTAG00000012341.6.
DR GeneID; 282419; -.
DR KEGG; bta:282419; -.
DR CTD; 1457; -.
DR VEuPathDB; HostDB:ENSBTAG00000012341; -.
DR eggNOG; KOG0668; Eukaryota.
DR GeneTree; ENSGT00390000004215; -.
DR InParanoid; P68399; -.
DR OMA; KSWHSFV; -.
DR OrthoDB; 5472858at2759; -.
DR Reactome; R-BTA-1483191; Synthesis of PC.
DR Reactome; R-BTA-201688; WNT mediated activation of DVL.
DR Reactome; R-BTA-2514853; Condensation of Prometaphase Chromosomes.
DR Reactome; R-BTA-6804756; Regulation of TP53 Activity through Phosphorylation.
DR Reactome; R-BTA-6814122; Cooperation of PDCL (PhLP1) and TRiC/CCT in G-protein beta folding.
DR Reactome; R-BTA-8934903; Receptor Mediated Mitophagy.
DR Reactome; R-BTA-8939243; RUNX1 interacts with co-factors whose precise effect on RUNX1 targets is not known.
DR Reactome; R-BTA-8948751; Regulation of PTEN stability and activity.
DR Proteomes; UP000009136; Chromosome 13.
DR Bgee; ENSBTAG00000012341; Expressed in conceptus and 106 other cell types or tissues.
DR ExpressionAtlas; P68399; baseline and differential.
DR GO; GO:0005829; C:cytosol; IBA:GO_Central.
DR GO; GO:0005634; C:nucleus; IBA:GO_Central.
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:0106310; F:protein serine kinase activity; IEA:RHEA.
DR GO; GO:0004674; F:protein serine/threonine kinase activity; ISS:UniProtKB.
DR GO; GO:0006915; P:apoptotic process; IEA:UniProtKB-KW.
DR GO; GO:0007049; P:cell cycle; IEA:UniProtKB-KW.
DR GO; GO:0006302; P:double-strand break repair; ISS:UniProtKB.
DR GO; GO:0043154; P:negative regulation of cysteine-type endopeptidase activity involved in apoptotic process; ISS:UniProtKB.
DR GO; GO:0018105; P:peptidyl-serine phosphorylation; ISS:UniProtKB.
DR GO; GO:1905337; P:positive regulation of aggrephagy; ISS:UniProtKB.
DR GO; GO:0030307; P:positive regulation of cell growth; ISS:UniProtKB.
DR GO; GO:0008284; P:positive regulation of cell population proliferation; ISS:UniProtKB.
DR GO; GO:0045732; P:positive regulation of protein catabolic process; ISS:UniProtKB.
DR GO; GO:0030177; P:positive regulation of Wnt signaling pathway; ISS:UniProtKB.
DR GO; GO:0006468; P:protein phosphorylation; ISS:UniProtKB.
DR GO; GO:0051726; P:regulation of cell cycle; IBA:GO_Central.
DR GO; GO:1905818; P:regulation of chromosome separation; ISS:UniProtKB.
DR GO; GO:0048511; P:rhythmic process; IEA:UniProtKB-KW.
DR GO; GO:0016055; P:Wnt signaling pathway; IEA:UniProtKB-KW.
DR CDD; cd14132; STKc_CK2_alpha; 1.
DR Gene3D; 1.10.510.10; Transferase(Phosphotransferase) domain 1; 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; CASEIN KINASE II SUBUNIT ALPHA; 1.
DR PANTHER; PTHR24054:SF16; CASEIN KINASE II SUBUNIT ALPHA-RELATED; 1.
DR Pfam; PF00069; Pkinase; 1.
DR SMART; SM00220; S_TKc; 1.
DR SUPFAM; SSF56112; Protein kinase-like (PK-like); 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 Apoptosis; ATP-binding; Biological rhythms; Cell cycle;
KW Direct protein sequencing; Kinase; Nucleotide-binding; Nucleus;
KW Phosphoprotein; Reference proteome; Serine/threonine-protein kinase;
KW Transcription; Transcription regulation; Transferase;
KW Wnt signaling pathway.
FT CHAIN 1..391
FT /note="Casein kinase II subunit alpha"
FT /id="PRO_0000085882"
FT DOMAIN 39..324
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT REGION 36..41
FT /note="Interaction with beta subunit"
FT /evidence="ECO:0000250"
FT ACT_SITE 156
FT /note="Proton acceptor"
FT BINDING 45..53
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 68
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT MOD_RES 344
FT /note="Phosphothreonine; by CDK1"
FT /evidence="ECO:0000250|UniProtKB:P68400"
FT MOD_RES 360
FT /note="Phosphothreonine; by CDK1"
FT /evidence="ECO:0000250|UniProtKB:P68400"
FT MOD_RES 362
FT /note="Phosphoserine; by CDK1"
FT /evidence="ECO:0000250|UniProtKB:P68400"
FT MOD_RES 370
FT /note="Phosphoserine; by CDK1"
FT /evidence="ECO:0000250|UniProtKB:P68400"
FT CONFLICT 382
FT /note="P -> S (in Ref. 3; AAI12817)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 391 AA; 45144 MW; D3B6F5D13FF7422D CRC64;
MSGPVPSRAR VYTDVNTHRP REYWDYESHV VEWGNQDDYQ LVRKLGRGKY SEVFEAINIT
NNEKVVVKIL KPVKKKKIKR EIKILENLRG GPNIITLADI VKDPVSRTPA LVFEHVNNTD
FKQLYQTLTD YDIRFYMYEI LKALDYCHSM GIMHRDVKPH NVMIDHEHRK LRLIDWGLAE
FYHPGQEYNV RVASRYFKGP ELLVDYQMYD YSLDMWSLGC MLASMIFRKE PFFHGHDNYD
QLVRIAKVLG TEDLYDYIDK YNIELDPRFN DILGRHSRKR WERFVHSENQ HLVSPEALDF
LDKLLRYDHQ SRLTAREAME HPYFYTVVKD QARMGSSSMP GGSTPVSSAN MMSGISSVPT
PSPLGPLAGS PVIAAANPLG MPVPAAAGAQ Q
//
