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) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › 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. Interacts with SNAI1 (via zinc fingers). Ref.3 Ref.7 Ref.9 Ref.10 Ref.15
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.
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	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	DNA repair Traceable author statement Ref.1. Source: ProtInc G2/M transition of mitotic cell cycle Traceable author statement. Source: Reactome cellular protein localization Inferred from electronic annotation. Source: Compara negative regulation of Wnt receptor signaling pathway Inferred from electronic annotation. Source: Compara positive regulation of canonical Wnt receptor signaling pathway Inferred from electronic annotation. Source: Compara positive regulation of proteasomal ubiquitin-dependent protein catabolic process Inferred from sequence or structural similarity. Source: UniProtKB signal transduction Traceable author statement Ref.1. Source: ProtInc
Cellular_component	cytosol Traceable author statement. Source: Reactome nucleus Inferred from sequence or structural similarity. Source: UniProtKB ribonucleoprotein complex Inferred from electronic annotation. Source: Compara
Molecular_function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW protein serine/threonine kinase activity Traceable author statement Ref.1. Source: UniProtKB
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
AXIN1	O15169	4	EBI-749343,EBI-710484
HSP90AB1	P08238	2	EBI-749343,EBI-352572
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

343

1

Phosphoserine Ref.11 Ref.13

Modified residue

354

1

Phosphoserine Ref.11 Ref.13

Modified residue

362

1

Phosphothreonine Ref.11

Modified residue

363

1

Phosphoserine Ref.11 Ref.12 Ref.17

Modified residue

389

1

Phosphoserine Ref.14

Natural variations

Natural variant

256

1

R → L in a lung adenocarcinoma sample; somatic mutation. Ref.18

VAR_042082

Natural variant

413

1

H → R. Ref.18
Corresponds to variant rs35665927 [ dbSNP | Ensembl ].

VAR_042083

Secondary structure

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416

Helix Strand Turn

Details...

Turn

6 – 8

3

Beta strand

14 – 16

3

Beta strand

22 – 28

7

Turn

29 – 31

3

Beta strand

35 – 41

7

Helix

51 – 56

6

Turn

57 – 61

5

Beta strand

68 – 74

7

Beta strand

77 – 83

7

Helix

89 – 95

7

Turn

96 – 98

3

Helix

102 – 120

19

Turn

121 – 123

3

Helix

131 – 133

3

Beta strand

134 – 136

3

Helix

139 – 141

3

Beta strand

145 – 147

3

Beta strand

154 – 157

4

Turn

159 – 161

3

Helix

177 – 179

3

Helix

182 – 185

4

Helix

192 – 208

17

Turn

212 – 215

4

Helix

221 – 234

14

Helix

237 – 240

4

Turn

241 – 243

3

Helix

246 – 255

10

Helix

266 – 280

15

Helix

289 – 291

3

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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [Abstract] Cited for: ROLE IN WNT SIGNALING.
[9]	"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] [Europe PMC] [Abstract] Cited for: INTERACTION WITH DBNDD2.
[10]	"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] [Europe PMC] [Abstract] Cited for: INTERACTION WITH LRP5 AND LRP6.
[11]	"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] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-343; SER-354; THR-362 AND SER-363, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[12]	"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] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-363, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[13]	"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] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-343 AND SER-354, MASS SPECTROMETRY.
[14]	"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] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-389, MASS SPECTROMETRY. Tissue: Leukemic T-cell.
[15]	"Role of CK1 in GSK3beta-mediated phosphorylation and degradation of snail." Xu Y., Lee S.H., Kim H.S., Kim N.H., Piao S., Park S.H., Jung Y.S., Yook J.I., Park B.J., Ha N.C. Oncogene 29:3124-3133(2010) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH SNAI1.
[16]	"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] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[17]	"System-wide temporal characterization of the proteome and phosphoproteome of human embryonic stem cell differentiation." Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B. Sci. Signal. 4:RS3-RS3(2011) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-363, MASS SPECTROMETRY.
[18]	"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] [Europe PMC] [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

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
4HNI	X-ray	2.74	A/B	1-294	[»]
4HOK	X-ray	2.77	A/C/E/G/I/K/M/O/Q/S/U/W	1-294	[»]

ProteinModelPortal

P49674.

ModBase

Search...

Protein-protein interaction databases

IntAct

P49674. 49 interactions.

MINT

MINT-1444044.

STRING

9606.ENSP00000352929.

PTM databases

PhosphoSite

P49674.

Polymorphism databases

DMDM

1346369.

Proteomic databases

PaxDb

P49674.

PRIDE

P49674.

Protocols and materials databases

DNASU

1454.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000359867; ENSP00000352929; ENSG00000213923.
ENST00000396832; ENSP00000380044; ENSG00000213923.
ENST00000400206; ENSP00000383067; ENSG00000213923.
ENST00000403904; ENSP00000384074; ENSG00000213923.

GeneID

1454.

KEGG

hsa:1454.

UCSC

uc003avj.3. human.

Organism-specific databases

CTD

1454.

GeneCards

GC22M038686.

H-InvDB

HIX0080286.

HGNC

HGNC:2453. CSNK1E.

HPA

CAB009626.
HPA026288.

MIM

600863. gene.

neXtProt

NX_P49674.

PharmGKB

PA26953.

GenAtlas

Search...

Phylogenomic databases

eggNOG

COG0515.

HOGENOM

HOG000182055.

HOVERGEN

HBG000176.

InParanoid

P49674.

KO

K08960.

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_115566. Cell Cycle.
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.
IPR008271. Ser/Thr_kinase_AS.
[Graphical view]

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

BindingDB

P49674.

ChEMBL

CHEMBL4937.

ChiTaRS

CSNK1E. human.

GenomeRNAi

1454.

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:	May 1, 2013
This is version 136 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.