Reviewed, UniProtKB/Swiss-Prot P49674 (KC1E_HUMAN)

Names and origin

Protein names

Recommended name:
    Casein kinase I isoform epsilon
      Short name=CKI-epsilon
      Short name=CKIe
    EC=2.7.11.1

Gene names

Name:

CSNK1E

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

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

Protein attributes

Sequence length	416 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
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. Can phosphorylate a large number of proteins. Participates in Wnt signaling. Phosphorylates DVL1. Central component of the circadian clock. May act as a negative regulator of circadian rhythmicity by phosphorylating PER1 and PER2. Retains PER1 in the cytoplasm. Inhibits cytokine-induced granuloytic differentiation.
Catalytic activity	ATP + a protein = ADP + a phosphoprotein.
Subunit structure	Monomer. Component of the circadian core oscillator, which includes the CRY proteins, CLOCK, or NPAS2, BMAL1 or BMAL2, CSNK1D and/or CSNK1E, TIMELESS and the PER proteins. Interacts directly with PER1 and PER2 which may lead to their degradation. Interacts with ANKRD6 and SOCS3.
Subcellular location	CytoplasmBy similarity.
Tissue specificity	Expressed in all tissues examined, including brain, heart, lung, liver, pancreas, kidney, placenta and skeletal muscle. Expressed in monocytes and lymphocytes but not in granulocytes.
Induction	Down-regulated during granulocytic differentiation.
Post-translational modification	Autophosphorylated By similarity.
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
Cellular component	Cytoplasm
Coding sequence diversity	Polymorphism
Ligand	ATP-binding Nucleotide-binding
Molecular function	Kinase Serine/threonine-protein kinase Transferase
PTM	Phosphoprotein
Gene Ontology (GO)
Uncategorized	casein kinase I activity Ref.1 Traceable author statement. Source: ProtInc
Biological process	DNA repair Ref.1 Traceable author statement. Source: ProtInc protein amino acid phosphorylation Ref.1 Traceable author statement. Source: ProtInc signal transduction Ref.1 Traceable author statement. Source: ProtInc
Molecular function	protein binding Inferred from physical interaction. Source: IntAct
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
APC	P25054	1	EBI-749343,EBI-727707
MCC	P23508	1	EBI-749343,EBI-307531
PER2	O15055	1	EBI-749343,EBI-1054296

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view
Molecule processing
	Chain	1 – 416	416	Casein kinase I isoform epsilon
Regions
	Domain	9 – 277	269	Protein kinase
	Nucleotide binding	15 – 23	9	ATP By similarity
Sites
	Active site	128	1	Proton acceptor By similarity
	Binding site	38	1	ATP By similarity
Amino acid modifications
	Modified residue	343	1	Phosphoserine
	Modified residue	362	1	Phosphothreonine
	Modified residue	363	1	Phosphoserine
	Modified residue	389	1	Phosphoserine
Natural variations
	Natural variant	256	1	R → L in a lung adenocarcinoma sample; somatic mutation.
	Natural variant	413	1	H → R

Sequences

	Sequence		Length	Mass (Da)
	P49674-1 [UniParc]. Last modified February 1, 1996. Version 1. Checksum: EE1B1698AE914324	FASTA	416	47,315
	10 20 30 40 50 60 MELRVGNKYR LGRKIGSGSF GDIYLGANIA SGEEVAIKLE CVKTKHPQLH IESKFYKMMQ 70 80 90 100 110 120 GGVGIPSIKW CGAEGDYNVM VMELLGPSLE DLFNFCSRKF SLKTVLLLAD QMISRIEYIH 130 140 150 160 170 180 SKNFIHRDVK PDNFLMGLGK KGNLVYIIDF GLAKKYRDAR THQHIPYREN KNLTGTARYA 190 200 210 220 230 240 SINTHLGIEQ SRRDDLESLG YVLMYFNLGS LPWQGLKAAT KRQKYERISE KKMSTPIEVL 250 260 270 280 290 300 CKGYPSEFST YLNFCRSLRF DDKPDYSYLR QLFRNLFHRQ GFSYDYVFDW NMLKFGAARN 310 320 330 340 350 360 PEDVDRERRE HEREERMGQL RGSATRALPP GPPTGATANR LRSAAEPVAS TPASRIQPAG 370 380 390 400 410 NTSPRAISRV DRERKVSMRL HRGAPANVSS SDLTGRQEVS RIPASQTSVP FDHLGK

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"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]. Tissue: Placenta.
[2]	"Casein kinase I epsilon from HeLa cell." Ono K., Murata-Hori M., Hosoya H. Submitted (MAR-1999) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[3]	"Involvement of casein kinase Iepsilon in cytokine-induced granulocytic differentiation." Okamura A., Iwata N., Nagata A., Tamekane A., Shimoyama M., Gomyo H., Yakushijin K., Urahama N., Hamaguchi M., Fukui C., Chihara K., Ito M., Matsui T. Blood 103:2997-3004(2004) [PubMed: 15070676] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], INTERACTION WITH SOCS3, INDUCTION, FUNCTION. Tissue: Hematopoietic stem cell.
[4]	"A genome annotation-driven approach to cloning the human ORFeome." Collins J.E., Wright C.L., Edwards C.A., Davis M.P., Grinham J.A., Cole C.G., Goward M.E., Aguado B., Mallya M., Mokrab Y., Huckle E.J., Beare D.M., Dunham I. Genome Biol. 5:RESEARCH84.1-RESEARCH84.11(2004) [PubMed: 15461802] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[5]	"The DNA sequence of human chromosome 22." Dunham I., Hunt A.R., Collins J.E., Bruskiewich R., Beare D.M., Clamp M., Smink L.J., Ainscough R., Almeida J.P., Babbage A.K., Bagguley C., Bailey J., Barlow K.F., Bates K.N., Beasley O.P., Bird C.P., Blakey S.E., Bridgeman A.M. , Buck D., Burgess J., Burrill W.D., Burton J., Carder C., Carter N.P., Chen Y., Clark G., Clegg S.M., Cobley V.E., Cole C.G., Collier R.E., Connor R., Conroy D., Corby N.R., Coville G.J., Cox A.V., Davis J., Dawson E., Dhami P.D., Dockree C., Dodsworth S.J., Durbin R.M., Ellington A.G., Evans K.L., Fey J.M., Fleming K., French L., Garner A.A., Gilbert J.G.R., Goward M.E., Grafham D.V., Griffiths M.N.D., Hall C., Hall R.E., Hall-Tamlyn G., Heathcott R.W., Ho S., Holmes S., Hunt S.E., Jones M.C., Kershaw J., Kimberley A.M., King A., Laird G.K., Langford C.F., Leversha M.A., Lloyd C., Lloyd D.M., Martyn I.D., Mashreghi-Mohammadi M., Matthews L.H., Mccann O.T., Mcclay J., Mclaren S., McMurray A.A., Milne S.A., Mortimore B.J., Odell C.N., Pavitt R., Pearce A.V., Pearson D., Phillimore B.J.C.T., Phillips S.H., Plumb R.W., Ramsay H., Ramsey Y., Rogers L., Ross M.T., Scott C.E., Sehra H.K., Skuce C.D., Smalley S., Smith M.L., Soderlund C., Spragon L., Steward C.A., Sulston J.E., Swann R.M., Vaudin M., Wall M., Wallis J.M., Whiteley M.N., Willey D.L., Williams L., Williams S.A., Williamson H., Wilmer T.E., Wilming L., Wright C.L., Hubbard T., Bentley D.R., Beck S., Rogers J., Shimizu N., Minoshima S., Kawasaki K., Sasaki T., Asakawa S., Kudoh J., Shintani A., Shibuya K., Yoshizaki Y., Aoki N., Mitsuyama S., Roe B.A., Chen F., Chu L., Crabtree J., Deschamps S., Do A., Do T., Dorman A., Fang F., Fu Y., Hu P., Hua A., Kenton S., Lai H., Lao H.I., Lewis J., Lewis S., Lin S.-P., Loh P., Malaj E., Nguyen T., Pan H., Phan S., Qi S., Qian Y., Ray L., Ren Q., Shaull S., Sloan D., Song L., Wang Q., Wang Y., Wang Z., White J., Willingham D., Wu H., Yao Z., Zhan M., Zhang G., Chissoe S., Murray J., Miller N., Minx P., Fulton R., Johnson D., Bemis G., Bentley D., Bradshaw H., Bourne S., Cordes M., Du Z., Fulton L., Goela D., Graves T., Hawkins J., Hinds K., Kemp K., Latreille P., Layman D., Ozersky P., Rohlfing T., Scheet P., Walker C., Wamsley A., Wohldmann P., Pepin K., Nelson J., Korf I., Bedell J.A., Hillier L.W., Mardis E., Waterston R., Wilson R., Emanuel B.S., Shaikh T., Kurahashi H., Saitta S., Budarf M.L., McDermid H.E., Johnson A., Wong A.C.C., Morrow B.E., Edelmann L., Kim U.J., Shizuya H., Simon M.I., Dumanski J.P., Peyrard M., Kedra D., Seroussi E., Fransson I., Tapia I., Bruder C.E., O'Brien K.P., Wilkinson P., Bodenteich A., Hartman K., Hu X., Khan A.S., Lane L., Tilahun Y., Wright H. Nature 402:489-495(1999) [PubMed: 10591208] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]	"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]. Tissue: Lung.
[7]	"Phosphorylation and destabilization of human period I clock protein by human casein kinase I epsilon." Keesler G.A., Camacho F., Guo Y., Virshup D., Mondadori C., Yao Z. NeuroReport 11:951-955(2000) [PubMed: 10790862] [Abstract] Cited for: INTERACTION WITH PER1.
[8]	"Casein kinase I epsilon enhances the binding of Dvl-1 to Frat-1 and is essential for Wnt-3a-induced accumulation of beta-catenin." Hino S., Michiue T., Asashima M., Kikuchi A. J. Biol. Chem. 278:14066-14073(2003) [PubMed: 12556519] [Abstract] Cited for: ROLE IN WNT SIGNALING.
[9]	"Large-scale characterization of HeLa cell nuclear phosphoproteins." Beausoleil S.A., Jedrychowski M., Schwartz D., Elias J.E., Villen J., Li J., Cohn M.A., Cantley L.C., Gygi S.P. Proc. Natl. Acad. Sci. U.S.A. 101:12130-12135(2004) [PubMed: 15302935] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-363, MASS SPECTROMETRY. Tissue: Epithelium.
[10]	"Global, in vivo, and site-specific phosphorylation dynamics in signaling networks." Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M. Cell 127:635-648(2006) [PubMed: 17081983] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-362, 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 SER-363, MASS SPECTROMETRY.
[12]	"Combining protein-based IMAC, peptide-based IMAC, and MudPIT for efficient phosphoproteomic analysis." Cantin G.T., Yi W., Lu B., Park S.K., Xu T., Lee J.-D., Yates J.R. III J. Proteome Res. 7:1346-1351(2008) [PubMed: 18220336] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-343 AND SER-389, MASS SPECTROMETRY.
[13]	"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: VARIANTS [LARGE SCALE ANALYSIS] LEU-256 AND ARG-413.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBLGenBankDDBJ	L37043 mRNA. Translation: AAC41761.1. AB024597 mRNA. Translation: BAA92345.1. AB091043 mRNA. Translation: BAC10902.1. CR456429 mRNA. Translation: CAG30315.1. AL020993 Genomic DNA. Translation: CAA15888.1. BC006490 mRNA. Translation: AAH06490.1.
PIR	I61744.
RefSeq	NP_001885.1. NP_689407.1.
UniGene	Hs.474833
3D structure databases
HSSP	HSSP built from PDB template 1CKJ based on UniProtKB Q06486.
SMR	P49674. Positions 1-296.
ModBase	Search...
Protein-protein interaction databases
IntAct	P49674.
PTM databases
PhosphoSite	P49674.
Genome annotation databases
Ensembl	ENSG00000213923. Homo sapiens. [Contig view]
GeneID	1454.
KEGG	hsa:1454.
Organism-specific databases
H-InvDB	HIX0016469.
HGNC	HGNC:2453. CSNK1E.
HPA	CAB009626.
MIM	600863. gene.
PharmGKB	PA26953.
GenAtlas	Search...
GeneCards	Search...
Phylogenomic databases
HOGENOM	P49674.
HOVERGEN	P49674.
Gene expression databases
ArrayExpress	P49674.
CleanEx	HS_CSNK1E.
GermOnline	ENSG00000100181. Homo sapiens.
Family and domain databases
InterPro	IPR000719. Prot_kinase_core. IPR017441. Protein_kinase_ATP_bd_CS. IPR017442. Se/Thr_pkinase-rel. IPR008271. Ser_thr_pkin_AS. [Graphical view]
Pfam	PF00069. Pkinase. 1 hit. [Graphical view]
ProDom	PD000001. Prot_kinase. 1 hit. [Graphical view] [Entries sharing at least one domain]
PROSITE	PS00107. PROTEIN_KINASE_ATP. 1 hit. PS50011. PROTEIN_KINASE_DOM. 1 hit. PS00108. PROTEIN_KINASE_ST. 1 hit. [Graphical view]
BLOCKS	Search...
Other Resources
LinkHub	P49674.
SOURCE	Search...
ProtoNet	Search...

Entry information

Entry name

KC1E_HUMAN

Accession

Primary (citable) accession number: P49674

Entry history

Integrated into UniProtKB/Swiss-Prot:	February 1, 1996
Last sequence update:	February 1, 1996
Last modified:	July 22, 2008
This is version 88 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)