Reviewed, UniProtKB/Swiss-Prot P48729 (KC1A_HUMAN)

Names and origin

Protein names

Recommended name:
    Casein kinase I isoform alpha
      Short name=CKI-alpha
    EC=2.7.11.1
Alternative name(s):
    CK1

Gene names

Name:

CSNK1A1

Organism

Homo sapiens (Human) [Complete proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	337 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	Casein kinases are operationally defined by their preferential utilization of acidic proteins such as caseins as substrates. It can phosphorylate a large number of proteins. Participates in Wnt signaling. Phosphorylates CTNNB1 at 'Ser-45'. May play a role in segregating chromosomes during mitosis. Ref.9
Catalytic activity	ATP + a protein = ADP + a phosphoprotein.
Subunit structure	Monomer. Interacts with the Axin complex.
Subcellular location	Cytoplasm. Cytoplasm › cytoskeleton › centrosome. Kinetochore. Note: Localizes to the centrosome in interphase cells, and to kinetochore fibers during mitosis.
Sequence similarities	Belongs to the protein kinase superfamily. CK1 Ser/Thr protein kinase family. Casein kinase I subfamily. Contains 1 protein kinase domain.

Ontologies

Keywords
Biological process	Cell cycle Cell division Mitosis Wnt signaling pathway
Cellular component	Cytoplasm Cytoskeleton Kinetochore
Coding sequence diversity	Alternative splicing Polymorphism
Ligand	ATP-binding Nucleotide-binding
Molecular function	Kinase Serine/threonine-protein kinase Transferase
PTM	Acetylation Phosphoprotein
Technical term	Complete proteome Direct protein sequencing
Gene Ontology (GO)
Biological process	Wnt receptor signaling pathway Inferred from electronic annotation. Source: UniProtKB-KW protein amino acid phosphorylation Traceable author statement. Source: ProtInc
Cellular component	cytosol Ref.9 Inferred from Experiment. Source: Reactome
Molecular function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW protein binding Inferred from physical interaction. Source: IntAct protein serine/threonine kinase activity Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
RIPK1	Q13546	4	EBI-1383726,EBI-358507
TNFRSF1A	P19438	1	EBI-1383726,EBI-299451

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: P48729-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

Isoform 2 (identifier: P48729-2)

The sequence of this isoform differs from the canonical sequence as follows:
     152-152: K → KCLESPVGKRKRSMTVSTSQDPSFSGLNQ

Note: Phosphorylated on Ser-156.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 337	337	Casein kinase I isoform alpha		PRO_0000192822
Regions
	Domain	17 – 285	269	Protein kinase
	Nucleotide binding	23 – 31	9	ATP By similarity
Sites
	Active site	136	1	Proton acceptor By similarity
	Binding site	46	1	ATP By similarity
Amino acid modifications
	Modified residue	3	1	Phosphoserine
	Modified residue	8	1	N6-acetyllysine Ref.18
	Modified residue	105	1	Phosphoserine Ref.17
	Modified residue	311	1	Phosphoserine Ref.13
	Modified residue	313	1	Phosphoserine Ref.15
	Modified residue	321	1	Phosphothreonine Ref.13 Ref.15 Ref.10 Ref.11 Ref.12
	Modified residue	327	1	Phosphothreonine Ref.13
	Modified residue	332	1	Phosphoserine
Natural variations
	Alternative sequence	152	1	K → KCLESPVGKRKRSMTVSTSQ DPSFSGLNQ in isoform 2.		VSP_035455
	Natural variant	297	1	D → H in a breast pleomorphic lobular carcinoma sample; somatic mutation. Ref.19		VAR_042073
Experimental info
	Sequence conflict	45	1	V → L in CAA56710. Ref.1
	Sequence conflict	74	1	P → T in AAV38633. Ref.4
	Sequence conflict	122	1	S → A AA sequence Ref.8
	Sequence conflict	129	1	T → TK AA sequence Ref.8
	Sequence conflict	231	1	Q → K in AAH08717. Ref.7
	Sequence conflict	250	1	K → E in AAY84562. Ref.5
	Sequence conflict	330	1	T → S in CAA56710. Ref.1
	Sequence conflict	330	1	T → S in AAV38632. Ref.4
	Sequence conflict	330	1	T → S in AAV38633. Ref.4

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified May 23, 2003. Version 2. Checksum: 1B2085AE33CAFAC2	FASTA	337	38,915
	10 20 30 40 50 60 MASSSGSKAE FIVGGKYKLV RKIGSGSFGD IYLAINITNG EEVAVKLESQ KARHPQLLYE 70 80 90 100 110 120 SKLYKILQGG VGIPHIRWYG QEKDYNVLVM DLLGPSLEDL FNFCSRRFTM KTVLMLADQM 130 140 150 160 170 180 ISRIEYVHTK NFIHRDIKPD NFLMGIGRHC NKLFLIDFGL AKKYRDNRTR QHIPYREDKN 190 200 210 220 230 240 LTGTARYASI NAHLGIEQSR RDDMESLGYV LMYFNRTSLP WQGLKAATKK QKYEKISEKK 250 260 270 280 290 300 MSTPVEVLCK GFPAEFAMYL NYCRGLRFEE APDYMYLRQL FRILFRTLNH QYDYTFDWTM 310 320 330 LKQKAAQQAA SSSGQGQQAQ TPTGKQTDKT KSNMKGF
	Isoform 2. Checksum: 11756FB15947D9F5	FASTA	365	41,937
	10 20 30 40 50 60 MASSSGSKAE FIVGGKYKLV RKIGSGSFGD IYLAINITNG EEVAVKLESQ KARHPQLLYE 70 80 90 100 110 120 SKLYKILQGG VGIPHIRWYG QEKDYNVLVM DLLGPSLEDL FNFCSRRFTM KTVLMLADQM 130 140 150 160 170 180 ISRIEYVHTK NFIHRDIKPD NFLMGIGRHC NKCLESPVGK RKRSMTVSTS QDPSFSGLNQ 190 200 210 220 230 240 LFLIDFGLAK KYRDNRTRQH IPYREDKNLT GTARYASINA HLGIEQSRRD DMESLGYVLM 250 260 270 280 290 300 YFNRTSLPWQ GLKAATKKQK YEKISEKKMS TPVEVLCKGF PAEFAMYLNY CRGLRFEEAP 310 320 330 340 350 360 DYMYLRQLFR ILFRTLNHQY DYTFDWTMLK QKAAQQAASS SGQGQQAQTP TGKQTDKTKS NMKGF

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Cloning and chromosomal localization of the gene coding for human protein kinase CK1." Tapia C., Featherstone T., Gomez C., Taillon-Miller P., Allende C.C., Allende J.E. FEBS Lett. 349:307-312(1994) [PubMed: 8050587] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). Tissue: Brain.
[2]	"Isolation and characterization of human casein kinase I epsilon (CKI), a novel member of the CKI gene family." Fish K.J., Cegielska A., Getman M.E., Landes G.M., Virshup D.M. J. Biol. Chem. 270:14875-14883(1995) [PubMed: 7797465] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). Tissue: Placenta.
[3]	"Cloning of human full open reading frames in Gateway(TM) system entry vector (pDONR201)." Halleck A., Ebert L., Mkoundinya M., Schick M., Eisenstein S., Neubert P., Kstrang K., Schatten R., Shen B., Henze S., Mar W., Korn B., Zuo D., Hu Y., LaBaer J. Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
[4]	"Cloning of human full-length CDSs in BD Creator(TM) system donor vector." Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S., Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y., Phelan M., Farmer A. Submitted (OCT-2004) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
[5]	Lin L., Nong W., Zhou G., Ke R., Shen C., Zhong G., Zheng Z., Liang M., Huang B., Li H., Yang S. Submitted (JUN-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
[6]	Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[7]	"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: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). Tissue: Lung.
[8]	"Cell cycle-dependent localization of casein kinase I to mitotic spindles." Brockman J.L., Gross S.D., Sussman M.R., Anderson R.A. Proc. Natl. Acad. Sci. U.S.A. 89:9454-9458(1992) [PubMed: 1409656] [Abstract] Cited for: PROTEIN SEQUENCE OF 65-83; 111-152 AND 179-204, FUNCTION, SUBCELLULAR LOCATION.
[9]	"Control of beta-catenin phosphorylation/degradation by a dual-kinase mechanism." Liu C., Li Y., Semenov M., Han C., Baeg G.-H., Tan Y., Zhang Z., Lin X., He X. Cell 108:837-847(2002) [PubMed: 11955436] [Abstract] Cited for: ROLE IN WNT SIGNALING.
[10]	"Phosphoproteome analysis of the human mitotic spindle." Nousiainen M., Sillje H.H.W., Sauer G., Nigg E.A., Koerner R. Proc. Natl. Acad. Sci. U.S.A. 103:5391-5396(2006) [PubMed: 16565220] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-321, MASS SPECTROMETRY. Tissue: Epithelium.
[11]	"Proteomics analysis of protein kinases by target class-selective prefractionation and tandem mass spectrometry." Wissing J., Jaensch L., Nimtz M., Dieterich G., Hornberger R., Keri G., Wehland J., Daub H. Mol. Cell. Proteomics 6:537-547(2007) [PubMed: 17192257] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-321, MASS SPECTROMETRY.
[12]	"Evaluation of the low-specificity protease elastase for large-scale phosphoproteome analysis." Wang B., Malik R., Nigg E.A., Korner R. Anal. Chem. 80:9526-9533(2008) [PubMed: 19007248] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-321, MASS SPECTROMETRY.
[13]	"Kinase-selective enrichment enables quantitative phosphoproteomics of the kinome across the cell cycle." Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R., Greff Z., Keri G., Stemmann O., Mann M. Mol. Cell 31:438-448(2008) [PubMed: 18691976] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-311; THR-321 AND THR-327, PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-156 (ISOFORM 2), MASS SPECTROMETRY.
[14]	Colinge J., Superti-Furga G., Bennett K.L. Submitted (OCT-2008) to UniProtKB Cited for: IDENTIFICATION [LARGE SCALE ANALYSIS], MASS SPECTROMETRY.
[15]	"Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach." Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S. Anal. Chem. 81:4493-4501(2009) [PubMed: 19413330] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-313 AND THR-321, MASS SPECTROMETRY.
[16]	"Large-scale proteomics analysis of the human kinome." Oppermann F.S., Gnad F., Olsen J.V., Hornberger R., Greff Z., Keri G., Mann M., Daub H. Mol. Cell. Proteomics 8:1751-1764(2009) [PubMed: 19369195] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-3; SER-311; THR-321 AND SER-332, MASS SPECTROMETRY.
[17]	"Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions." Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., Rodionov V., Han D.K. Sci. Signal. 2:RA46-RA46(2009) [PubMed: 19690332] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-105, MASS SPECTROMETRY. Tissue: T-cell.
[18]	"Lysine acetylation targets protein complexes and co-regulates major cellular functions." Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T., Olsen J.V., Mann M. Science 325:834-840(2009) [PubMed: 19608861] [Abstract] Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-8, MASS SPECTROMETRY.
[19]	"Patterns of somatic mutation in human cancer genomes." Greenman C., Stephens P., Smith R., Dalgliesh G.L., Hunter C., Bignell G., Davies H., Teague J., Butler A., Stevens C., Edkins S., O'Meara S., Vastrik I., Schmidt E.E., Avis T., Barthorpe S., Bhamra G., Buck G. , Choudhury B., Clements J., Cole J., Dicks E., Forbes S., Gray K., Halliday K., Harrison R., Hills K., Hinton J., Jenkinson A., Jones D., Menzies A., Mironenko T., Perry J., Raine K., Richardson D., Shepherd R., Small A., Tofts C., Varian J., Webb T., West S., Widaa S., Yates A., Cahill D.P., Louis D.N., Goldstraw P., Nicholson A.G., Brasseur F., Looijenga L., Weber B.L., Chiew Y.-E., DeFazio A., Greaves M.F., Green A.R., Campbell P., Birney E., Easton D.F., Chenevix-Trench G., Tan M.-H., Khoo S.K., Teh B.T., Yuen S.T., Leung S.Y., Wooster R., Futreal P.A., Stratton M.R. Nature 446:153-158(2007) [PubMed: 17344846] [Abstract] Cited for: VARIANT [LARGE SCALE ANALYSIS] HIS-297.
+	Additional computationally mapped references.

Web resources

Atlas of Genetics and Cytogenetics in Oncology and Haematology

Cross-references

Sequence databases
EMBL GenBank DDBJ	X80693 mRNA. Translation: CAA56710.1. L37042 mRNA. Translation: AAC41760.1. CR542206 mRNA. Translation: CAG47002.1. BT019829 mRNA. Translation: AAV38632.1. BT019830 mRNA. Translation: AAV38633.1. DQ082865 mRNA. Translation: AAY84562.1. CH471062 Genomic DNA. Translation: EAW61769.1. BC008717 mRNA. Translation: AAH08717.1.
IPI	IPI00183400. IPI00448798.
PIR	A57011. S46254.
RefSeq	NP_001020276.1. NP_001883.4.
UniGene	Hs.529862 Hs.712555
3D structure databases
SMR	P48729. Positions 10-302.
ModBase	Search...
Protein-protein interaction databases
IntAct	P48729. 7 interactions.
STRING	P48729.
PTM databases
PhosphoSite	P48729.
Proteomic databases
PRIDE	P48729.
Genome annotation databases
Ensembl	ENST00000377843; ENSP00000367074; ENSG00000113712; Homo sapiens. [Genome view]
GeneID	1452.
KEGG	hsa:1452.
UCSC	uc003lqx.1. human.
Organism-specific databases
CTD	1452.
GeneCards	GC05M148854.
H-InvDB	HIX0005302.
HGNC	HGNC:2451. CSNK1A1.
HPA	CAB016680.
MIM	600505. gene.
PharmGKB	PA26951.
GenAtlas	Search...
Phylogenomic databases
eggNOG	prNOG17212.
HOVERGEN	P48729.
OMA	MIGRIEY.
OrthoDB	EOG9Z0DRP.
PhylomeDB	P48729.
Enzyme and pathway databases
BRENDA	2.7.11.1. 247.
Pathway_Interaction_DB	wnt_canonical_pathway. Canonical Wnt signaling pathway. foxopathway. FoxO family signaling. hedgehog_glipathway. Hedgehog signaling events mediated by Gli proteins. wnt_calcium_pathway. Noncanonical Wnt signaling pathway. ps1pathway. Presenilin action in Notch and Wnt signaling. nfat_3pathway. Role of Calcineurin-dependent NFAT signaling in lymphocytes.
Reactome	REACT_11045. Signaling by Wnt.
Gene expression databases
ArrayExpress	P48729.
Bgee	P48729.
CleanEx	HS_CSNK1A1.
Genevestigator	P48729.
GermOnline	ENSG00000113712. Homo sapiens.
Family and domain databases
InterPro	IPR011009. Kinase-like_dom. IPR000719. Prot_kinase_cat_dom. IPR017441. Protein_kinase_ATP_BS. IPR017442. Se/Thr_prot_kinase-like_dom. IPR008271. Ser/Thr_prot_kinase_AS. [Graphical view]
Pfam	PF00069. Pkinase. 1 hit. [Graphical view]
PROSITE	PS00107. PROTEIN_KINASE_ATP. 1 hit. PS50011. PROTEIN_KINASE_DOM. 1 hit. PS00108. PROTEIN_KINASE_ST. 1 hit. [Graphical view]
ProtoNet	Search...
Other Resources
NextBio	5955.
SOURCE	Search...

Entry information

Entry name

KC1A_HUMAN

Accession

Primary (citable) accession number: P48729
Secondary accession number(s): Q4JJA0 , Q5U046, Q5U047, Q6FGA2, Q96HD2, Q9UDK3

Entry history

Integrated into UniProtKB/Swiss-Prot:	February 1, 1996
Last sequence update:	May 23, 2003
Last modified:	February 9, 2010
This is version 103 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.