CSK21_RAT
ID CSK21_RAT Reviewed; 391 AA.
AC P19139; Q5BKC1;
DT 01-NOV-1990, integrated into UniProtKB/Swiss-Prot.
DT 01-FEB-1995, sequence version 2.
DT 03-AUG-2022, entry version 185.
DE RecName: Full=Casein kinase II subunit alpha;
DE Short=CK II alpha;
DE EC=2.7.11.1 {ECO:0000269|PubMed:19330005};
GN Name=Csnk2a1;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Liver;
RX PubMed=8173590;
RA Ahmed K., Davis A., Hanten J., Lambert D., McIvor R.S., Goueli S.A.;
RT "Cloning of cDNAs encoding the alpha and beta subunits of rat casein kinase
RT 2 (CK-2): investigation of molecular regulation of CK-2 by androgens in rat
RT ventral prostate.";
RL Cell. Mol. Biol. Res. 39:451-462(1993).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Spleen;
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 [3]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 8-391.
RX PubMed=2752008; DOI=10.1021/bi00435a066;
RA Meisner H., Heller-Harrison R., Buxton J., Czech M.P.;
RT "Molecular cloning of the human casein kinase II alpha subunit.";
RL Biochemistry 28:4072-4076(1989).
RN [4]
RP PROTEIN SEQUENCE OF 22-68; 90-107; 173-191; 229-244; 248-268 AND 284-306,
RP FUNCTION, AND CATALYTIC ACTIVITY.
RX PubMed=19330005; DOI=10.1038/nsmb.1578;
RA Tamaru T., Hirayama J., Isojima Y., Nagai K., Norioka S., Takamatsu K.,
RA Sassone-Corsi P.;
RT "CK2alpha phosphorylates BMAL1 to regulate the mammalian clock.";
RL Nat. Struct. Mol. Biol. 16:446-448(2009).
RN [5]
RP FUNCTION IN APOPTOSIS.
RX PubMed=12191471; DOI=10.1016/s1097-2765(02)00600-7;
RA Li P.F., Li J., Mueller E.C., Otto A., Dietz R., von Harsdorf R.;
RT "Phosphorylation by protein kinase CK2: a signaling switch for the caspase-
RT inhibiting protein ARC.";
RL Mol. Cell 10:247-258(2002).
RN [6]
RP X-RAY CRYSTALLOGRAPHY (3.0 ANGSTROMS) OF 1-335.
RX DOI=10.1007/S11434-008-0580-2;
RA Zhou W., Qin X., Yan X., Xie X., Li L., Fang S., Long J., Adelman J.,
RA Tang W.-J., Shen Y.;
RT "Crystal structures of catalytic and regulatory subunits of rat protein
RT kinase CK2.";
RL Chin. Sci. Bull. 54:220-226(2009).
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 (By similarity). Regulates numerous
CC cellular processes, such as cell cycle progression, apoptosis and
CC transcription, as well as viral infection (By similarity). May act as a
CC regulatory node which integrates and coordinates numerous signals
CC leading to an appropriate cellular response (By similarity). During
CC mitosis, functions as a component of the p53/TP53-dependent spindle
CC assembly checkpoint (SAC) that maintains cyclin-B-CDK1 activity and G2
CC arrest in response to spindle damage (By similarity). Also required for
CC p53/TP53-mediated apoptosis, phosphorylating 'Ser-392' of p53/TP53
CC following UV irradiation (By similarity). Can also negatively regulate
CC apoptosis (PubMed:12191471). Phosphorylates the caspases CASP9 and
CC CASP2 and the apoptotic regulator NOL3 (PubMed:12191471).
CC Phosphorylation protects CASP9 from cleavage and activation by CASP8,
CC and inhibits the dimerization of CASP2 and activation of CASP8
CC (PubMed:12191471). Regulates transcription by direct phosphorylation of
CC RNA polymerases I, II, III and IV (By similarity). Also phosphorylates
CC and regulates numerous transcription factors including NF-kappa-B,
CC STAT1, CREB1, IRF1, IRF2, ATF1, ATF4, SRF, MAX, JUN, FOS, MYC and MYB
CC (By similarity). Phosphorylates Hsp90 and its co-chaperones FKBP4 and
CC CDC37, which is essential for chaperone function (By similarity).
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 (By similarity). Regulates Wnt signaling by
CC phosphorylating CTNNB1 and the transcription factor LEF1 (By
CC similarity). Acts as an ectokinase that phosphorylates several
CC extracellular proteins (By similarity). During viral infection,
CC phosphorylates various proteins involved in the viral life cycles of
CC EBV, HSV, HBV, HCV, HIV, CMV and HPV (By similarity). Phosphorylates
CC PML at 'Ser-565' and primes it for ubiquitin-mediated degradation (By
CC similarity). Plays an important role in the circadian clock function by
CC phosphorylating ARNTL/BMAL1 at 'Ser-90' which is pivotal for its
CC interaction with CLOCK and which controls CLOCK nuclear entry
CC (PubMed:19330005). {ECO:0000250|UniProtKB:P68400,
CC ECO:0000269|PubMed:12191471, ECO:0000269|PubMed:19330005}.
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:0000269|PubMed:19330005};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:17990;
CC Evidence={ECO:0000269|PubMed:19330005};
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:0000269|PubMed:19330005};
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}.
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DR EMBL; L15618; AAA74462.1; -; mRNA.
DR EMBL; BC091130; AAH91130.1; -; mRNA.
DR EMBL; J02853; -; NOT_ANNOTATED_CDS; mRNA.
DR PIR; B30319; B30319.
DR RefSeq; NP_446276.1; NM_053824.2.
DR RefSeq; XP_006235282.1; XM_006235220.3.
DR RefSeq; XP_006235283.1; XM_006235221.3.
DR PDB; 2R7I; X-ray; 3.00 A; A/B/C/D=1-335.
DR PDBsum; 2R7I; -.
DR AlphaFoldDB; P19139; -.
DR SMR; P19139; -.
DR BioGRID; 250484; 7.
DR IntAct; P19139; 6.
DR MINT; P19139; -.
DR STRING; 10116.ENSRNOP00000007558; -.
DR BindingDB; P19139; -.
DR ChEMBL; CHEMBL3988629; -.
DR iPTMnet; P19139; -.
DR PhosphoSitePlus; P19139; -.
DR jPOST; P19139; -.
DR PaxDb; P19139; -.
DR PRIDE; P19139; -.
DR Ensembl; ENSRNOT00000113326; ENSRNOP00000092799; ENSRNOG00000005276.
DR GeneID; 116549; -.
DR KEGG; rno:116549; -.
DR UCSC; RGD:621663; rat.
DR CTD; 1457; -.
DR RGD; 621663; Csnk2a1.
DR eggNOG; KOG0668; Eukaryota.
DR GeneTree; ENSGT00390000004215; -.
DR HOGENOM; CLU_000288_70_4_1; -.
DR InParanoid; P19139; -.
DR OMA; ACEKRPQ; -.
DR OrthoDB; 1098380at2759; -.
DR PhylomeDB; P19139; -.
DR TreeFam; TF300483; -.
DR BRENDA; 2.7.11.1; 5301.
DR Reactome; R-RNO-1483191; Synthesis of PC.
DR Reactome; R-RNO-201688; WNT mediated activation of DVL.
DR Reactome; R-RNO-2514853; Condensation of Prometaphase Chromosomes.
DR Reactome; R-RNO-445144; Signal transduction by L1.
DR Reactome; R-RNO-6804756; Regulation of TP53 Activity through Phosphorylation.
DR Reactome; R-RNO-6814122; Cooperation of PDCL (PhLP1) and TRiC/CCT in G-protein beta folding.
DR Reactome; R-RNO-8934903; Receptor Mediated Mitophagy.
DR Reactome; R-RNO-8939243; RUNX1 interacts with co-factors whose precise effect on RUNX1 targets is not known.
DR Reactome; R-RNO-8948751; Regulation of PTEN stability and activity.
DR EvolutionaryTrace; P19139; -.
DR PRO; PR:P19139; -.
DR Proteomes; UP000002494; Chromosome 3.
DR Bgee; ENSRNOG00000005276; Expressed in skeletal muscle tissue and 19 other tissues.
DR Genevisible; P19139; RN.
DR GO; GO:0000785; C:chromatin; IDA:RGD.
DR GO; GO:0005737; C:cytoplasm; IDA:RGD.
DR GO; GO:0005829; C:cytosol; IBA:GO_Central.
DR GO; GO:0005634; C:nucleus; IDA:RGD.
DR GO; GO:0016581; C:NuRD complex; ISO:RGD.
DR GO; GO:0005886; C:plasma membrane; IDA:RGD.
DR GO; GO:0005956; C:protein kinase CK2 complex; ISO:RGD.
DR GO; GO:0016580; C:Sin3 complex; ISO:RGD.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0008013; F:beta-catenin binding; ISO:RGD.
DR GO; GO:0042802; F:identical protein binding; ISO:RGD.
DR GO; GO:0016301; F:kinase activity; ISO:RGD.
DR GO; GO:0047485; F:protein N-terminus binding; ISO:RGD.
DR GO; GO:0019888; F:protein phosphatase regulator activity; ISO:RGD.
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:0043021; F:ribonucleoprotein complex binding; IDA:RGD.
DR GO; GO:0006915; P:apoptotic process; IEA:UniProtKB-KW.
DR GO; GO:0007049; P:cell cycle; IEA:UniProtKB-KW.
DR GO; GO:0021987; P:cerebral cortex development; IEP:RGD.
DR GO; GO:0097421; P:liver regeneration; IEP:RGD.
DR GO; GO:0043154; P:negative regulation of cysteine-type endopeptidase activity involved in apoptotic process; ISS:UniProtKB.
DR GO; GO:2000059; P:negative regulation of ubiquitin-dependent protein catabolic process; ISO:RGD.
DR GO; GO:0018105; P:peptidyl-serine phosphorylation; ISS:UniProtKB.
DR GO; GO:0018107; P:peptidyl-threonine phosphorylation; ISO:RGD.
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:0046777; P:protein autophosphorylation; ISO:RGD.
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:1903076; P:regulation of protein localization to plasma membrane; IGI:ARUK-UCL.
DR GO; GO:0033574; P:response to testosterone; IEP:RGD.
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 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 3D-structure; 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_0000085886"
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 ACT_SITE 156
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT ECO:0000255|PROSITE-ProRule:PRU10027"
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 STRAND 10..12
FT /evidence="ECO:0007829|PDB:2R7I"
FT TURN 15..18
FT /evidence="ECO:0007829|PDB:2R7I"
FT HELIX 21..24
FT /evidence="ECO:0007829|PDB:2R7I"
FT HELIX 26..28
FT /evidence="ECO:0007829|PDB:2R7I"
FT HELIX 36..38
FT /evidence="ECO:0007829|PDB:2R7I"
FT STRAND 39..43
FT /evidence="ECO:0007829|PDB:2R7I"
FT STRAND 52..58
FT /evidence="ECO:0007829|PDB:2R7I"
FT TURN 59..61
FT /evidence="ECO:0007829|PDB:2R7I"
FT STRAND 64..69
FT /evidence="ECO:0007829|PDB:2R7I"
FT HELIX 75..88
FT /evidence="ECO:0007829|PDB:2R7I"
FT STRAND 97..102
FT /evidence="ECO:0007829|PDB:2R7I"
FT STRAND 109..114
FT /evidence="ECO:0007829|PDB:2R7I"
FT HELIX 122..125
FT /evidence="ECO:0007829|PDB:2R7I"
FT HELIX 130..149
FT /evidence="ECO:0007829|PDB:2R7I"
FT HELIX 159..161
FT /evidence="ECO:0007829|PDB:2R7I"
FT STRAND 162..165
FT /evidence="ECO:0007829|PDB:2R7I"
FT TURN 166..169
FT /evidence="ECO:0007829|PDB:2R7I"
FT STRAND 170..173
FT /evidence="ECO:0007829|PDB:2R7I"
FT HELIX 195..197
FT /evidence="ECO:0007829|PDB:2R7I"
FT HELIX 200..203
FT /evidence="ECO:0007829|PDB:2R7I"
FT HELIX 212..226
FT /evidence="ECO:0007829|PDB:2R7I"
FT STRAND 230..233
FT /evidence="ECO:0007829|PDB:2R7I"
FT HELIX 240..249
FT /evidence="ECO:0007829|PDB:2R7I"
FT HELIX 251..260
FT /evidence="ECO:0007829|PDB:2R7I"
FT HELIX 267..271
FT /evidence="ECO:0007829|PDB:2R7I"
FT HELIX 281..284
FT /evidence="ECO:0007829|PDB:2R7I"
FT TURN 287..292
FT /evidence="ECO:0007829|PDB:2R7I"
FT HELIX 295..304
FT /evidence="ECO:0007829|PDB:2R7I"
FT HELIX 309..311
FT /evidence="ECO:0007829|PDB:2R7I"
FT HELIX 315..319
FT /evidence="ECO:0007829|PDB:2R7I"
FT HELIX 322..324
FT /evidence="ECO:0007829|PDB:2R7I"
FT HELIX 325..328
FT /evidence="ECO:0007829|PDB:2R7I"
SQ SEQUENCE 391 AA; 45073 MW; 83A4E2CC80824F66 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 QARMSSAGMA GGSTPVSSAN MMSGISSVPT
PSPLGPLAGS PVIAAANSLG IPVPAAAGAQ Q
