CSK21_RABIT
ID CSK21_RABIT Reviewed; 391 AA.
AC P33674;
DT 01-FEB-1994, integrated into UniProtKB/Swiss-Prot.
DT 01-FEB-1994, sequence version 1.
DT 03-AUG-2022, entry version 144.
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;
OS Oryctolagus cuniculus (Rabbit).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Lagomorpha; Leporidae; Oryctolagus.
OX NCBI_TaxID=9986;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=8444352; DOI=10.1016/0378-1119(93)90407-t;
RA Gupta S.K., Singh J.P.;
RT "PCR cloning and sequence of two cDNAs encoding the alpha and beta subunits
RT of rabbit casein kinase-II.";
RL Gene 124:287-290(1993).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=New Zealand white;
RA Gupta S.K., Rothfuss K.J., Singh J.P.;
RL Submitted (MAR-1996) to the EMBL/GenBank/DDBJ databases.
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, ATF4, SRF, MAX, JUN, FOS, MYC and MYB. Phosphorylates
CC Hsp90 and its co-chaperones FKBP4 and CDC37, which is essential for
CC chaperone function. Mediates sequential phosphorylation of FNIP1,
CC promoting its gradual interaction with Hsp90, leading to activate both
CC kinase and non-kinase client proteins of Hsp90. Regulates Wnt signaling
CC by phosphorylating CTNNB1 and the transcription factor LEF1. Acts as an
CC ectokinase that phosphorylates several extracellular proteins. During
CC viral infection, phosphorylates various proteins involved in the viral
CC life cycles of EBV, HSV, HBV, HCV, HIV, CMV and HPV. Phosphorylates PML
CC 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 (By
CC similarity). {ECO:0000250|UniProtKB:P19139,
CC 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}.
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DR EMBL; S56527; AAB25554.1; -; mRNA.
DR EMBL; M98451; AAA91891.1; -; mRNA.
DR PIR; JN0555; JN0555.
DR RefSeq; NP_001153756.1; NM_001160284.1.
DR AlphaFoldDB; P33674; -.
DR SMR; P33674; -.
DR STRING; 9986.ENSOCUP00000019122; -.
DR iPTMnet; P33674; -.
DR GeneID; 100301533; -.
DR KEGG; ocu:100301533; -.
DR CTD; 1457; -.
DR eggNOG; KOG0668; Eukaryota.
DR InParanoid; P33674; -.
DR OrthoDB; 1098380at2759; -.
DR BRENDA; 2.7.11.1; 1749.
DR Proteomes; UP000001811; Unplaced.
DR GO; GO:0005634; C:nucleus; IEA:UniProtKB-SubCell.
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: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: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: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 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 2: Evidence at transcript level;
KW Apoptosis; ATP-binding; Biological rhythms; Cell cycle; Kinase;
KW Nucleotide-binding; Nucleus; Phosphoprotein; Reference proteome;
KW Serine/threonine-protein kinase; Transcription; Transcription regulation;
KW Transferase; Wnt signaling pathway.
FT CHAIN 1..391
FT /note="Casein kinase II subunit alpha"
FT /id="PRO_0000085885"
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 /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"
SQ SEQUENCE 391 AA; 45116 MW; 5212943C906905D4 CRC64;
MSGPVPSRVR VYTDVNTHRP REYWDYESHV VEWGNQDDYQ LVRKLGRGKY SEVFEAINIT
NNEKVVVKIL KPVKKKKIKR EIKILENLRG GPNIITLADI VKDPASRTPA LAFEHVNNTD
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
