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P49674 (KC1E_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified March 19, 2014. Version 145. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (7) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Casein kinase I isoform epsilon

Short name=CKI-epsilon
Short name=CKIe
EC=2.7.11.1
Gene names
Name:CSNK1E
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length416 AA.
Sequence statusComplete.
Protein existenceEvidence 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 Ref.11

Catalytic activity

ATP + a protein = ADP + a phosphoprotein.

Enzyme regulation

Phosphorylation leads to a decrease of the catalytic activity. Ref.11

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.17

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 Ref.11

Post-translational modification

Autophosphorylated. Partially dephosphorylated by PPP5C. Ref.11

Sequence similarities

Belongs to the protein kinase superfamily. CK1 Ser/Thr protein kinase family. Casein kinase I subfamily.

Contains 1 protein kinase domain.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 416416Casein kinase I isoform epsilon
PRO_0000192837

Regions

Domain9 – 277269Protein kinase
Nucleotide binding15 – 239ATP By similarity

Sites

Active site1281Proton acceptor By similarity
Binding site381ATP By similarity

Amino acid modifications

Modified residue3431Phosphoserine Ref.12 Ref.15
Modified residue3541Phosphoserine Ref.12 Ref.15
Modified residue3621Phosphothreonine Ref.12
Modified residue3631Phosphoserine Ref.12 Ref.13 Ref.19
Modified residue3891Phosphoserine Ref.16

Natural variations

Natural variant2561R → L in a lung adenocarcinoma sample; somatic mutation. Ref.21
VAR_042082
Natural variant4131H → R. Ref.21
Corresponds to variant rs35665927 [ dbSNP | Ensembl ].
VAR_042083

Secondary structure

..................................................... 416
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
P49674 [UniParc].

Last modified February 1, 1996. Version 1.
Checksum: EE1B1698AE914324

FASTA41647,315
        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 

« Hide

References

« Hide '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. expand/collapse author list , 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]"Posttranslational regulation of the mammalian circadian clock by cryptochrome and protein phosphatase 5."
Partch C.L., Shields K.F., Thompson C.L., Selby C.P., Sancar A.
Proc. Natl. Acad. Sci. U.S.A. 103:10467-10472(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, AUTOPHOSPHORYLATION, DEPHOSPHORYLATION BY PPP5C, ENZYME REGULATION.
[12]"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, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[13]"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, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[14]"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] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[15]"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, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[16]"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, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Leukemic T-cell.
[17]"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.
[18]"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].
[19]"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, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[20]"Structural basis for the potent and selective inhibition of casein kinase 1 epsilon."
Long A.M., Zhao H., Huang X.
J. Med. Chem. 55:10307-10311(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.74 ANGSTROMS) OF 1-294 ALONE AND IN COMPLEX WITH INHIBITOR.
[21]"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. expand/collapse author list , 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.
PIRI61744.
RefSeqNP_001885.1. NM_001894.4.
NP_689407.1. NM_152221.2.
UniGeneHs.474833.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
4HNIX-ray2.74A/B1-294[»]
4HOKX-ray2.77A/C/E/G/I/K/M/O/Q/S/U/W1-294[»]
ProteinModelPortalP49674.
SMRP49674. Positions 4-294.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid107838. 299 interactions.
IntActP49674. 70 interactions.
MINTMINT-1444044.
STRING9606.ENSP00000352929.

Chemistry

BindingDBP49674.
ChEMBLCHEMBL4937.
GuidetoPHARMACOLOGY1998.

PTM databases

PhosphoSiteP49674.

Polymorphism databases

DMDM1346369.

Proteomic databases

PaxDbP49674.
PRIDEP49674.

Protocols and materials databases

DNASU1454.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000359867; ENSP00000352929; ENSG00000213923.
ENST00000396832; ENSP00000380044; ENSG00000213923.
ENST00000400206; ENSP00000383067; ENSG00000213923.
ENST00000403904; ENSP00000384074; ENSG00000213923.
GeneID1454.
KEGGhsa:1454.
UCSCuc003avj.3. human.

Organism-specific databases

CTD1454.
GeneCardsGC22M038686.
H-InvDBHIX0080286.
HGNCHGNC:2453. CSNK1E.
HPACAB009626.
HPA026288.
MIM600863. gene.
neXtProtNX_P49674.
PharmGKBPA26953.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG0515.
HOGENOMHOG000182055.
HOVERGENHBG000176.
InParanoidP49674.
KOK08960.
OrthoDBEOG7CZK5W.
PhylomeDBP49674.
TreeFamTF300544.

Enzyme and pathway databases

BRENDA2.7.11.1. 2681.
ReactomeREACT_115566. Cell Cycle.
REACT_24941. Circadian Clock.
SignaLinkP49674.

Gene expression databases

ArrayExpressP49674.
BgeeP49674.
CleanExHS_CSNK1E.
GenevestigatorP49674.

Family and domain databases

InterProIPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR008271. Ser/Thr_kinase_AS.
[Graphical view]
PfamPF00069. Pkinase. 1 hit.
[Graphical view]
SUPFAMSSF56112. SSF56112. 1 hit.
PROSITEPS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSCSNK1E. human.
GeneWikiCSNK1E.
GenomeRNAi1454.
NextBio5969.
PROP49674.
SOURCESearch...

Entry information

Entry nameKC1E_HUMAN
AccessionPrimary (citable) accession number: P49674
Entry history
Integrated into UniProtKB/Swiss-Prot: February 1, 1996
Last sequence update: February 1, 1996
Last modified: March 19, 2014
This is version 145 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

Human and mouse protein kinases

Human and mouse protein kinases: classification and index

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 22

Human chromosome 22: entries, gene names and cross-references to MIM