Q60737 (CSK21_MOUSE) 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
Synonyms:	Ckiia

Organism

Mus musculus (Mouse) [Reference proteome]

Taxonomic identifier

10090 [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 › Mus › Mus

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.6 Ref.7
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. Interacts with PML By similarity. Ref.9
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.
Disruption phenotype	Embryonic lethality at 10.5 dpc. Ref.8
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	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 direct assay PubMed 18191828. Source: MGI 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 PubMed 12432063. Source: MGI
Molecular_function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW beta-catenin binding Inferred from direct assay PubMed 12432063. Source: MGI protein phosphatase regulator activity Inferred from direct assay PubMed 15284227. Source: MGI 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_0000085884
Regions
	Domain	39 – 324	286	Protein kinase
	Nucleotide binding	45 – 53	9	ATP By similarity
	Region	36 – 41	6	Interaction with beta subunit By similarity
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
Experimental info
	Sequence conflict	315	1	A → V in AAA64563. Ref.1
	Sequence conflict	323	1	Y → F in AAA64563. Ref.1
	Sequence conflict	330	1	D → N in AAA64563. Ref.1
	Sequence conflict	360	1	T → S in AAA64563. Ref.1
	Sequence conflict	384	1	P → Q in AAA64563. Ref.1

Sequences

	Sequence		Length	Mass (Da)
	Q60737 [UniParc]. Last modified July 27, 2011. Version 2. Checksum: C7A5F7CC8099230D	FASTA	391	45,134
	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 QARMSSTSMA GGSTPVSSAN MMSGISSVPT 370 380 390 PSPLGPLAGS PVIAAANSLG IPVPAAAGAQ Q

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Casein kinase II alpha transgene-induced murine lymphoma: relation to theileriosis in cattle." Seldin D.C., Leder P. Science 267:894-897(1995) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Strain: FVB/N. Tissue: Spleen.
[2]	"The transcriptional landscape of the mammalian genome." Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J. , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y. Science 309:1559-1563(2005) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Strain: C57BL/6J. Tissue: Inner ear and Liver.
[3]	"Lineage-specific biology revealed by a finished genome assembly of the mouse." Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X., Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y., Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S. , Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R., Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K., Eichler E.E., Ponting C.P. PLoS Biol. 7:E1000112-E1000112(2009) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. Strain: C57BL/6J.
[4]	Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C. Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]	"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]. Strain: C57BL/6 and FVB/N. Tissue: Mammary tumor.
[6]	"Endogenous protein kinase CK2 participates in Wnt signaling in mammary epithelial cells." Song D.H., Sussman D.J., Seldin D.C. J. Biol. Chem. 275:23790-23797(2000) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION.
[7]	"Phosphorylation of murine caspase-9 by the protein kinase casein kinase 2 regulates its cleavage by caspase-8." McDonnell M.A., Abedin M.J., Melendez M., Platikanova T.N., Ecklund J.R., Ahmed K., Kelekar A. J. Biol. Chem. 283:20149-20158(2008) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION IN APOPTOSIS.
[8]	"The alpha catalytic subunit of protein kinase CK2 is required for mouse embryonic development." Lou D.Y., Dominguez I., Toselli P., Landesman-Bollag E., O'Brien C., Seldin D.C. Mol. Cell. Biol. 28:131-139(2008) [PubMed] [Europe PMC] [Abstract] Cited for: DISRUPTION PHENOTYPE.
[9]	"Phosphorylation of serine 11 and serine 92 as new positive regulators of human Snail1 function: potential involvement of casein kinase-2 and the cAMP-activated kinase protein kinase A." MacPherson M.R., Molina P., Souchelnytskyi S., Wernstedt C., Martin-Perez J., Portillo F., Cano A. Mol. Biol. Cell 21:244-253(2010) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH SNAI1.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	U17112 mRNA. Translation: AAA64563.1. AK146032 mRNA. Translation: BAE26845.1. AK158077 mRNA. Translation: BAE34350.1. AL831735 Genomic DNA. Translation: CAM24731.1. CH466551 Genomic DNA. Translation: EDL05953.1. BC026149 mRNA. Translation: AAH26149.1. BC060742 mRNA. Translation: AAH60742.1. BC089343 mRNA. Translation: AAH89343.1.
IPI	IPI00120162.
PIR	I49141.
RefSeq	NP_031814.2. NM_007788.3.
UniGene	Mm.23692.
3D structure databases
ProteinModelPortal	Q60737.
SMR	Q60737. Positions 2-359.
ModBase	Search...
Protein-protein interaction databases
DIP	DIP-32409N.
IntAct	Q60737. 5 interactions.
MINT	MINT-121842.
PTM databases
PhosphoSite	Q60737.
Proteomic databases
PaxDb	Q60737.
PRIDE	Q60737.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENSMUST00000099224; ENSMUSP00000096829; ENSMUSG00000074698.
GeneID	12995.
KEGG	mmu:12995.
Organism-specific databases
CTD	1457.
MGI	MGI:88543. Csnk2a1.
Phylogenomic databases
eggNOG	COG0515.
GeneTree	ENSGT00390000004215.
HOGENOM	HOG000233021.
HOVERGEN	HBG107282.
InParanoid	Q8R0X4.
KO	K03097.
OMA	ITNNEKC.
Enzyme and pathway databases
BRENDA	2.7.11.1. 3474.
Gene expression databases
ArrayExpress	Q60737.
Bgee	Q60737.
CleanEx	MM_CSNK2A1.
Genevestigator	Q60737.
GermOnline	ENSMUSG00000057808. Mus musculus. ENSMUSG00000074698. Mus musculus.
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	Q60737.
ChEMBL	CHEMBL3537.
ChiTaRS	CSNK2A1. mouse.
NextBio	282804.
SOURCE	Search...

Entry information

Entry name

CSK21_MOUSE

Accession

Primary (citable) accession number: Q60737
Secondary accession number(s): Q8R0X4

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 15, 1998
Last sequence update:	July 27, 2011
Last modified:	May 1, 2013
This is version 121 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program