P19139 (CSK21_RAT) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Casein kinase II subunit alpha
Short name=CK II alpha
EC=2.7.11.1

Gene names

Name:

Csnk2a1

Organism

Rattus norvegicus (Rat) [Reference proteome]

Taxonomic identifier

10116 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Rattus

Protein attributes

Sequence length	391 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Catalytic subunit of a constitutively active serine/threonine-protein kinase complex that phosphorylates a large number of substrates containing acidic residues C-terminal to the phosphorylated serine or threonine. Regulates numerous cellular processes, such as cell cycle progression, apoptosis and transcription, as well as viral infection. May act as a regulatory node which integrates and coordinates numerous signals leading to an appropriate cellular response. During mitosis, functions as a component of the p53/TP53-dependent spindle assembly checkpoint (SAC) that maintains cyclin-B-CDK1 activity and G2 arrest in response to spindle damage. Also required for p53/TP53-mediated apoptosis, phosphorylating 'Ser-392' of p53/TP53 following UV irradiation. Can also negatively regulate apoptosis. Phosphorylates the caspases CASP9 and CASP2 and the apoptotic regulator NOL3. Phosphorylation protects CASP9 from cleavage and activation by CASP8, and inhibits the dimerization of CASP2 and activation of CASP8. Regulates transcription by direct phosphorylation of RNA polymerases I, II, III and IV. Also phosphorylates and regulates numerous transcription factors including NF-kappa-B, STAT1, CREB1, IRF1, IRF2, ATF1, SRF, MAX, JUN, FOS, MYC and MYB. Phosphorylates Hsp90 and its co-chaperones FKBP4 and CDC37, which is essential for chaperone function. Regulates Wnt signaling by phosphorylating CTNNB1 and the transcription factor LEF1. Acts as an ectokinase that phosphorylates several extracellular proteins. Phosphorylates PML at 'Ser-565' and primes it for ubiquitin-mediated degradation By similarity. Ref.4
Catalytic activity	ATP + a protein = ADP + a phosphoprotein.
Enzyme regulation	Constitutively active protein kinase whose activity is not directly affected by phosphorylation. Seems to be regulated by level of expression and localization By similarity.
Subunit structure	Heterotetramer composed of two catalytic subunits (alpha chain and/or alpha' chain) and two regulatory subunits (beta chains). The tetramer can exist as a combination of 2 alpha/2 beta, 2 alpha'/2 beta or 1 alpha/1 alpha'/2 beta subunits. Also part of a CK2-SPT16-SSRP1 complex composed of SSRP1, SUPT16H, CSNK2A1, CSNK2A2 and CSNK2B, which forms following UV irradiation. Interacts with RNPS1. Interacts with SNAI1 By similarity. Interacts with PML By similarity.
Post-translational modification	Phosphorylated at Thr-344, Thr-360, Ser-362 and Ser-370 by CDK1 in prophase and metaphase and dephosphorylated during anaphase. Phosphorylation does not directly affect casein kinase 2 activity, but may contribute to its regulation by forming binding sites for interacting proteins and/or targeting it to different compartments By similarity.
Miscellaneous	Can use both ATP and GTP as phosphoryl donors. Phosphorylation by casein kinase 2 has been estimated to represent up to one quarter of the eukaryotic phosphoproteome.
Sequence similarities	Belongs to the protein kinase superfamily. Ser/Thr protein kinase family. CK2 subfamily. Contains 1 protein kinase domain.

Ontologies

Keywords
Biological process	Apoptosis Cell cycle Transcription Transcription regulation Wnt signaling pathway
Ligand	ATP-binding Nucleotide-binding
Molecular function	Kinase Serine/threonine-protein kinase Transferase
PTM	Acetylation Phosphoprotein
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	Wnt receptor signaling pathway Inferred from electronic annotation. Source: UniProtKB-KW mitotic spindle checkpoint Inferred from sequence or structural similarity. Source: UniProtKB negative regulation of cysteine-type endopeptidase activity involved in apoptotic process Inferred from sequence or structural similarity. Source: UniProtKB positive regulation of Wnt receptor signaling pathway Inferred from sequence or structural similarity. Source: UniProtKB positive regulation of cell growth Inferred from sequence or structural similarity. Source: UniProtKB positive regulation of cell proliferation Inferred from sequence or structural similarity. Source: UniProtKB positive regulation of protein catabolic process Inferred from sequence or structural similarity. Source: UniProtKB protein autophosphorylation Inferred from electronic annotation. Source: Compara regulation of transcription, DNA-dependent Inferred from electronic annotation. Source: UniProtKB-KW transcription, DNA-dependent Inferred from electronic annotation. Source: UniProtKB-KW
Cellular_component	NuRD complex Inferred from electronic annotation. Source: Compara PcG protein complex Inferred from electronic annotation. Source: Compara Sin3 complex Inferred from electronic annotation. Source: Compara protein kinase CK2 complex Traceable author statement Ref.1. Source: RGD
Molecular_function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW protein phosphatase regulator activity Inferred from electronic annotation. Source: Compara protein serine/threonine kinase activity Inferred from sequence or structural similarity. Source: UniProtKB
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 391

391

Casein kinase II subunit alpha

PRO_0000085886

Regions

Domain

39 – 324

286

Protein kinase

Nucleotide binding

45 – 53

9

ATP By similarity

Region

36 – 41

6

Interaction with beta subunit

Sites

Active site

156

1

Proton acceptor By similarity

Binding site

68

1

ATP By similarity

Amino acid modifications

Modified residue

102

1

N6-acetyllysine By similarity

Modified residue

287

1

Phosphoserine By similarity

Modified residue

344

1

Phosphothreonine; by CDK1 By similarity

Modified residue

360

1

Phosphothreonine; by CDK1 By similarity

Modified residue

362

1

Phosphoserine; by CDK1 By similarity

Modified residue

370

1

Phosphoserine; by CDK1 By similarity

Secondary structure

1

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391

Helix Strand Turn

Details...

Beta strand

10 – 12

3

Turn

15 – 18

4

Helix

21 – 24

4

Helix

26 – 28

3

Helix

36 – 38

3

Beta strand

39 – 43

5

Beta strand

52 – 58

7

Turn

59 – 61

3

Beta strand

64 – 69

6

Helix

75 – 88

14

Beta strand

97 – 102

6

Beta strand

109 – 114

6

Helix

122 – 125

4

Helix

130 – 149

20

Helix

159 – 161

3

Beta strand

162 – 165

4

Turn

166 – 169

4

Beta strand

170 – 173

4

Helix

195 – 197

3

Helix

200 – 203

4

Helix

212 – 226

15

Beta strand

230 – 233

4

Helix

240 – 249

10

Helix

251 – 260

10

Helix

267 – 271

5

Helix

281 – 284

4

Turn

287 – 292

6

Helix

295 – 304

10

Helix

309 – 311

3

Helix

315 – 319

5

Helix

322 – 324

3

Helix

325 – 328

4

Sequences

	Sequence		Length	Mass (Da)
	P19139 [UniParc]. Last modified February 1, 1995. Version 2. Checksum: 83A4E2CC80824F66	FASTA	391	45,073
	10 20 30 40 50 60 MSGPVPSRAR VYTDVNTHRP REYWDYESHV VEWGNQDDYQ LVRKLGRGKY SEVFEAINIT 70 80 90 100 110 120 NNEKVVVKIL KPVKKKKIKR EIKILENLRG GPNIITLADI VKDPVSRTPA LVFEHVNNTD 130 140 150 160 170 180 FKQLYQTLTD YDIRFYMYEI LKALDYCHSM GIMHRDVKPH NVMIDHEHRK LRLIDWGLAE 190 200 210 220 230 240 FYHPGQEYNV RVASRYFKGP ELLVDYQMYD YSLDMWSLGC MLASMIFRKE PFFHGHDNYD 250 260 270 280 290 300 QLVRIAKVLG TEDLYDYIDK YNIELDPRFN DILGRHSRKR WERFVHSENQ HLVSPEALDF 310 320 330 340 350 360 LDKLLRYDHQ SRLTAREAME HPYFYTVVKD QARMSSAGMA GGSTPVSSAN MMSGISSVPT 370 380 390 PSPLGPLAGS PVIAAANSLG IPVPAAAGAQ Q

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Cloning of cDNAs encoding the alpha and beta subunits of rat casein kinase 2 (CK-2): investigation of molecular regulation of CK-2 by androgens in rat ventral prostate." Ahmed K., Davis A., Hanten J., Lambert D., McIvor R.S., Goueli S.A. Cell. Mol. Biol. Res. 39:451-462(1993) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Liver.
[2]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Spleen.
[3]	"Molecular cloning of the human casein kinase II alpha subunit." Meisner H., Heller-Harrison R., Buxton J., Czech M.P. Biochemistry 28:4072-4076(1989) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 8-391.
[4]	"Phosphorylation by protein kinase CK2: a signaling switch for the caspase-inhibiting protein ARC." Li P.F., Li J., Mueller E.C., Otto A., Dietz R., von Harsdorf R. Mol. Cell 10:247-258(2002) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION IN APOPTOSIS.
[5]	"Crystal structures of catalytic and regulatory subunits of rat protein kinase CK2." Zhou W., Qin X., Yan X., Xie X., Li L., Fang S., Long J., Adelman J., Tang W.-J., Shen Y. Chin. Sci. Bull. 54:220-226(2009) Cited for: X-RAY CRYSTALLOGRAPHY (3.0 ANGSTROMS) OF 1-335.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

L15618 mRNA. Translation: AAA74462.1.
BC091130 mRNA. Translation: AAH91130.1.
J02853 mRNA. No translation available.

IPI

IPI00192586.

PIR

B30319.

RefSeq

NP_446276.1. NM_053824.2.

UniGene

Rn.4231.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2R7I	X-ray	3.00	A/B/C/D	1-335	[»]

ProteinModelPortal

P19139.

SMR

P19139. Positions 2-334.

ModBase

Search...

Protein-protein interaction databases

IntAct

P19139. 3 interactions.

MINT

MINT-3372564.

STRING

10116.ENSRNOP00000007558.

PTM databases

PhosphoSite

P19139.

Proteomic databases

PaxDb

P19139.

PRIDE

P19139.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENSRNOT00000007558; ENSRNOP00000007558; ENSRNOG00000005276.

GeneID

116549.

KEGG

rno:116549.

UCSC

RGD:621663. rat.

Organism-specific databases

CTD

1457.

RGD

621663. Csnk2a1.

Phylogenomic databases

eggNOG

COG0515.

GeneTree

ENSGT00390000004215.

HOGENOM

HOG000233021.

HOVERGEN

HBG107282.

InParanoid

P19139.

KO

K03097.

OMA

ITNNEKC.

OrthoDB

EOG4J118H.

Enzyme and pathway databases

BRENDA

2.7.11.1. 5301.

Gene expression databases

ArrayExpress

P19139.

Genevestigator

P19139.

GermOnline

ENSRNOG00000005276. Rattus norvegicus.

Family and domain databases

InterPro

IPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_cat_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR002290. Ser/Thr_dual-sp_kinase_dom.
IPR008271. Ser/Thr_kinase_AS.
[Graphical view]

Pfam

PF00069. Pkinase. 1 hit.
[Graphical view]

SMART

SM00220. S_TKc. 1 hit.
[Graphical view]

SUPFAM

SSF56112. Kinase_like. 1 hit.

PROSITE

PS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

BindingDB

P19139.

ChEMBL

CHEMBL2661.

EvolutionaryTrace

P19139.

NextBio

619175.

Entry information

Entry name

CSK21_RAT

Accession

Primary (citable) accession number: P19139
Secondary accession number(s): Q5BKC1

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 1, 1990
Last sequence update:	February 1, 1995
Last modified:	May 1, 2013
This is version 116 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program