P49674 (KC1E_HUMAN) Reviewed, UniProtKB/Swiss-Prot

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.
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. Ref.3 Ref.8
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, DBNDD2, LRP5, LRP6 and SOCS3. Ref.3 Ref.7 Ref.10 Ref.12
Subcellular location	Cytoplasm By similarity. Nucleus By 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. Ref.3
Post-translational modification	Autophosphorylated By similarity. Ref.9 Ref.11 Ref.13 Ref.14 Ref.15 Ref.16 Ref.17 Ref.18 Ref.19 Ref.20
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 Nucleus
Coding sequence diversity	Polymorphism
Ligand	ATP-binding Nucleotide-binding
Molecular function	Kinase Serine/threonine-protein kinase Transferase
PTM	Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	DNA repair Traceable author statement. Source: ProtInc G2/M transition of mitotic cell cycle Traceable author statement. Source: Reactome positive regulation of proteasomal ubiquitin-dependent protein catabolic process Inferred from sequence or structural similarity. Source: UniProtKB signal transduction Traceable author statement. Source: ProtInc
Cellular component	cytosol Traceable author statement. Source: Reactome nucleus Inferred from sequence or structural similarity. Source: UniProtKB
Molecular function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW protein binding Inferred from physical interaction Ref.10. Source: UniProtKB protein serine/threonine kinase activity Traceable author statement Ref.1. Source: UniProtKB
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
MDM2	Q00987	3	EBI-749343,EBI-389668

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 416	416	Casein kinase I isoform epsilon		PRO_0000192837
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	323	1	Phosphoserine Ref.16 Ref.19
	Modified residue	343	1	Phosphoserine Ref.15 Ref.16 Ref.19
	Modified residue	350	1	Phosphoserine Ref.16
	Modified residue	351	1	Phosphothreonine Ref.14 Ref.16
	Modified residue	354	1	Phosphoserine Ref.14 Ref.16 Ref.19
	Modified residue	362	1	Phosphothreonine Ref.11 Ref.16 Ref.19
	Modified residue	363	1	Phosphoserine Ref.9 Ref.13 Ref.16 Ref.17 Ref.19
	Modified residue	389	1	Phosphoserine Ref.14 Ref.15 Ref.16 Ref.18 Ref.19 Ref.20
	Modified residue	391	1	Phosphoserine Ref.19
	Modified residue	405	1	Phosphoserine Ref.16 Ref.19
	Modified residue	407	1	Phosphothreonine Ref.19
	Modified residue	408	1	Phosphoserine Ref.16 Ref.19
Natural variations
	Natural variant	256	1	R → L in a lung adenocarcinoma sample; somatic mutation. Ref.22		VAR_042082
	Natural variant	413	1	H → R. Ref.22 Corresponds to variant rs35665927 [ dbSNP | Ensembl ].		VAR_042083

Sequences

	Sequence		Length	Mass (Da)
	P49674 [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:R84.1-R84.11(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: Cervix carcinoma.
[10]	"Dysbindin structural homologue CK1BP is an isoform-selective binding partner of human casein kinase-1." Yin H., Laguna K.A., Li G., Kuret J. Biochemistry 45:5297-5308(2006) [PubMed: 16618118] [Abstract] Cited for: INTERACTION WITH DBNDD2.
[11]	"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: Cervix carcinoma.
[12]	"Negative regulation of LRP6 function by casein kinase I epsilon phosphorylation." Swiatek W., Kang H., Garcia B.A., Shabanowitz J., Coombs G.S., Hunt D.F., Virshup D.M. J. Biol. Chem. 281:12233-12241(2006) [PubMed: 16513652] [Abstract] Cited for: INTERACTION WITH LRP5 AND LRP6.
[13]	"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. Tissue: Leukemic T-cell.
[14]	"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-351; SER-354 AND SER-389, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[15]	"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. Tissue: Cervix carcinoma.
[16]	"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-323; SER-343; SER-350; THR-351; SER-354; THR-362; SER-363; SER-389; SER-405 AND SER-408, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[17]	"A quantitative atlas of mitotic phosphorylation." Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P. Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed: 18669648] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-363, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[18]	"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-389, MASS SPECTROMETRY. Tissue: Embryonic kidney.
[19]	"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-323; SER-343; SER-354; THR-362; SER-363; SER-389; SER-391; SER-405; THR-407 AND SER-408, MASS SPECTROMETRY.
[20]	"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-389, MASS SPECTROMETRY. Tissue: Leukemic T-cell.
[21]	"Initial characterization of the human central proteome." Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J. BMC Syst. Biol. 5:17-17(2011) [PubMed: 21269460] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[22]	"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
EMBL GenBank DDBJ	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.
IPI	IPI00027729.
PIR	I61744.
RefSeq	NP_001885.1. NM_001894.4. NP_689407.1. NM_152221.2.
UniGene	Hs.474833.
3D structure databases
ProteinModelPortal	P49674.
SMR	P49674. Positions 1-296.
ModBase	Search...
Protein-protein interaction databases
IntAct	P49674. 10 interactions.
MINT	MINT-1444044.
STRING	P49674.
PTM databases
PhosphoSite	P49674.
Polymorphism databases
DMDM	1346369.
Proteomic databases
PRIDE	P49674.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000359867; ENSP00000352929; ENSG00000213923. ENST00000396832; ENSP00000380044; ENSG00000213923. ENST00000400206; ENSP00000383067; ENSG00000213923. ENST00000402865; ENSP00000385582; ENSG00000213923. ENST00000403904; ENSP00000384074; ENSG00000213923. ENST00000438038; ENSP00000387440; ENSG00000213923.
GeneID	1454.
KEGG	hsa:1454.
UCSC	uc003avj.1. human.
Organism-specific databases
CTD	1454.
GeneCards	GC22M038686.
H-InvDB	HIX0016469. HIX0080286.
HGNC	HGNC:2453. CSNK1E.
HPA	CAB009626. HPA026288.
MIM	600863. gene.
neXtProt	NX_P49674.
PharmGKB	PA26953.
GenAtlas	Search...
Phylogenomic databases
eggNOG	prNOG16963.
HOGENOM	HBG755340.
HOVERGEN	HBG000176.
InParanoid	P49674.
OrthoDB	EOG42V8G9.
PhylomeDB	P49674.
Enzyme and pathway databases
BRENDA	2.7.11.1. 2681.
Pathway_Interaction_DB	circadianpathway. Circadian rhythm pathway. foxopathway. FoxO family signaling. hedgehog_glipathway. Hedgehog signaling events mediated by Gli proteins.
Reactome	REACT_152. Cell Cycle, Mitotic. REACT_24941. Circadian Clock.
Gene expression databases
ArrayExpress	P49674.
Bgee	P49674.
CleanEx	HS_CSNK1E.
Genevestigator	P49674.
GermOnline	ENSG00000100181. Homo sapiens.
Family and domain databases
InterPro	IPR011009. Kinase-like_dom. IPR000719. Prot_kinase_cat_dom. IPR017441. Protein_kinase_ATP_BS. IPR017442. Se/Thr_kinase-like_dom. IPR008271. Ser/Thr_kinase_AS. [Graphical view]
KO	K08960.
Pfam	PF00069. Pkinase. 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
NextBio	5969.
SOURCE	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:	January 25, 2012
This is version 124 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

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.