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Reviewed, UniProtKB/Swiss-Prot P48730 (KC1D_HUMAN)

Last modified June 16, 2009. Version 90. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data | Customize display text xml rdf/xml gff fasta
Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Binary interactions · Alternative products · Sequence annotation (Features) · Sequences · References · Cross-references · Entry information · Relevant documents

Names and origin

Protein namesRecommended name:
    Casein kinase I isoform delta
      Short name=CKI-delta
      Short name=CKId
    EC=2.7.11.1
Gene names
Name: CSNK1D
OrganismHomo sapiens (Human)
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length415 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is not processed.
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. It can phosphorylate a large number of proteins. Participates in Wnt signaling. 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.

Catalytic activity

ATP + a protein = ADP + a phosphoprotein.

Enzyme regulation

Exhibits substrate-dependent heparin activation.

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. Ref.4

Subcellular location

Cytoplasm.

Tissue specificity

Expressed in all tissues examined, including brain, heart, lung, liver, pancreas, kidney, placenta and skeletal muscle. In blood, highly expressed in hemopioetic cells and mature granulocytes. Also found in monocytes and lymphocytes. Ref.2

Post-translational modification

Autophosphorylated on serine and threonine residues By similarity.

Involvement in disease

Defects in CSNK1D are a cause of familial advanced sleep-phase syndrome (FASPS) [MIM:604348]. FASPS is characterized by very early sleep onset and offset. Individuals are 'morning larks' with a 4 hours advance of the sleep, temperature and melatonin rhythms. 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.

Ontologies

Binary interactions

With

Entry

#Exp.

IntAct

Notes

MCCP235081EBI-751621,EBI-307531

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: P48730-1)

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: P48730-2)

The sequence of this isoform differs from the canonical sequence as follows:
     400-415: IPGRVASSGLQSVVHR → NSIPFEHHGK
Note: Phosphorylated on Ser-401.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 415415Casein kinase I isoform delta
PRO_0000192833

Regions

Domain9 – 277269Protein kinase
Nucleotide binding15 – 239ATP By similarity
Region317 – 34226Autoinhibitory By similarity

Sites

Active site1281Proton acceptor By similarity
Binding site381ATP By similarity

Amino acid modifications

Modified residue3281Phosphoserine Ref.8
Modified residue3311Phosphoserine Ref.8 Ref.6 Ref.9
Modified residue3471Phosphothreonine Ref.8 Ref.9
Modified residue3491Phosphothreonine Ref.9
Modified residue3501Phosphoserine Ref.8 Ref.5
Modified residue3821Phosphoserine Ref.8 Ref.6 Ref.9
Modified residue3831Phosphoserine Ref.8 Ref.7
Modified residue3841Phosphoserine Ref.8 Ref.9
Modified residue3871Phosphothreonine Ref.8
Modified residue3961Phosphoserine Ref.8
Modified residue3971Phosphothreonine Ref.8
Modified residue3981Phosphoserine Ref.8
Modified residue4061Phosphoserine Ref.8
Modified residue4071Phosphoserine Ref.8

Natural variations

Alternative sequence400 – 41516IPGRV…SVVHR → NSIPFEHHGK in isoform 2.
VSP_010253
Natural variant441T → A in FASPS. Ref.11
VAR_029075
Natural variant971S → C in breast cancer samples; infiltrating ductal carcinoma; somatic mutation. Ref.12 Ref.13
VAR_036451
Natural variant4011P → A Ref.13
VAR_042081

Experimental info

Sequence conflict3301A → D in AAC50807. Ref.1

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified January 27, 2003. Version 2.
Checksum: B97F1717A52466D2

FASTA41547,330
        10         20         30         40         50         60 
MELRVGNRYR LGRKIGSGSF GDIYLGTDIA AGEEVAIKLE CVKTKHPQLH IESKIYKMMQ 

        70         80         90        100        110        120 
GGVGIPTIRW 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 
CKGYPSEFAT YLNFCRSLRF DDKPDYSYLR QLFRNLFHRQ GFSYDYVFDW NMLKFGASRA 

       310        320        330        340        350        360 
ADDAERERRD REERLRHSRN PATRGLPSTA SGRLRGTQEV APPTPLTPTS HTANTSPRPV 

       370        380        390        400        410 
SGMERERKVS MRLHRGAPVN ISSSDLTGRQ DTSRMSTSQI PGRVASSGLQ SVVHR 

« Hide

Isoform 2.

Checksum: 970B55B1AF6B56DD
Show »

FASTA40946,832

References

« Hide 'large scale' references
[1]"Sequence analysis of the cDNA for the human casein kinase I delta (CSNK1D) gene and its chromosomal localization."
Kusuda J., Hidari N., Hidari M., Hashimoto K.
Genomics 32:140-143(1996) [PubMed: 8786104] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORM 1).
Tissue: Brain.
[2]"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] (ISOFORM 1), TISSUE SPECIFICITY.
Tissue: Hematopoietic stem cell.
[3]"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] (ISOFORMS 1 AND 2).
Tissue: Placenta and Spleen.
[4]"Human casein kinase Idelta phosphorylation of human circadian clock proteins period 1 and 2."
Camacho F., Cilio M., Guo Y., Virshup D.M., Patel K., Khorkova O., Styren S., Morse B., Yao Z., Keesler G.A.
FEBS Lett. 489:159-165(2001) [PubMed: 11165242] [Abstract]
Cited for: INTERACTION WITH PER1 AND PER2.
[5]"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 SER-350, MASS SPECTROMETRY.
Tissue: Epithelium.
[6]"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-331 AND SER-382, MASS SPECTROMETRY.
[7]"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-383, MASS SPECTROMETRY.
[8]"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-328; SER-331; THR-347; SER-382; SER-383; SER-384; THR-387; SER-396; THR-397; SER-398; SER-406 AND SER-407, PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-401 (ISOFORM 2), MASS SPECTROMETRY.
[9]"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-331; THR-347; THR-349; SER-382 AND SER-384, MASS SPECTROMETRY.
[10]Colinge J., Superti-Furga G., Bennett K.L.
Submitted (OCT-2008) to UniProtKB
Cited for: IDENTIFICATION [LARGE SCALE ANALYSIS], MASS SPECTROMETRY.
[11]"Functional consequences of a CKIdelta mutation causing familial advanced sleep phase syndrome."
Xu Y., Padiath Q.S., Shapiro R.E., Jones C.R., Wu S.C., Saigoh N., Saigoh K., Ptacek L.J., Fu Y.H.
Nature 434:640-644(2005) [PubMed: 15800623] [Abstract]
Cited for: VARIANT FASPS ALA-44.
[12]"The consensus coding sequences of human breast and colorectal cancers."
Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D., Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P., Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V. expand/collapse author list , Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H., Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W., Velculescu V.E.
Science 314:268-274(2006) [PubMed: 16959974] [Abstract]
Cited for: VARIANT [LARGE SCALE ANALYSIS] CYS-97.
[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. 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: 17344846] [Abstract]
Cited for: VARIANTS [LARGE SCALE ANALYSIS] CYS-97 AND ALA-401.
+Additional computationally mapped references.

Cross-references

Sequence databases

U29171 mRNA. Translation: AAC50807.1.
U31285 Genomic RNA. Translation: AAC50808.1.
AB091044 mRNA. Translation: BAC10903.1.
BC003558 mRNA. Translation: AAH03558.1.
BC015775 mRNA. Translation: AAH15775.1.
IPIIPI00011102.
IPI00234463.
PIRG01876.
RefSeqNP_001884.2.
NP_620693.1.
UniGeneHs.631725

3D structure databases

HSSPHSSP built from PDB template 1CKJ based on UniProtKB Q06486.
SMRP48730. Positions 1-296.
ModBaseSearch...

Protein-protein interaction databases

IntActP48730. 7 interactions.

PTM databases

PhosphoSiteP48730.

Proteomic databases

PRIDEP48730.

Genome annotation databases

EnsemblENSG00000141551. Homo sapiens. [Contig view]
GeneID1453.
KEGGhsa:1453.

Organism-specific databases

GeneCardsGC17M077795.
H-InvDBHIX0014253.
HGNCHGNC:2452. CSNK1D.
HPACAB015410.
MIM600864. gene.
604348. phenotype.
Orphanet164736. Advanced sleep-phase syndrome, familial.
PharmGKBPA26952.
GenAtlasSearch...

Phylogenomic databases

HOGENOMP48730.
HOVERGENP48730.
OMAP48730. RMSTSQR.

Enzyme and pathway databases

BRENDA2.7.11.1. 247.
Pathway_Interaction_DBfoxopathway. FoxO family signaling.
hedgehog_glipathway. Hedgehog signaling events mediated by Gli proteins.

Gene expression databases

ArrayExpressP48730.
BgeeP48730.
CleanExHS_CSNK1D.
GermOnlineENSG00000141551. Homo sapiens.

Family and domain databases

InterProIPR000719. Prot_kinase_core.
IPR017441. Protein_kinase_ATP_BS.
IPR017442. Se/Thr_pkinase-rel.
IPR008271. Ser_thr_pkin_AS.
[Graphical view]
PfamPF00069. Pkinase. 1 hit.
[Graphical view]
ProDomPD000001. Prot_kinase. 1 hit.
[Graphical view] [Entries sharing at least one domain]
PROSITEPS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
[Graphical view]
ProtoNetSearch...

Other Resources

NextBio5961.
SOURCESearch...

Entry information

Entry nameKC1D_HUMAN
AccessionPrimary (citable) accession number: P48730
Secondary accession number(s): Q96KZ6, Q9BTN5
Entry history
Integrated into UniProtKB/Swiss-Prot: February 1, 1996
Last sequence update: January 27, 2003
Last modified: June 16, 2009
This is version 90 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation projectHPI (Human Proteome Initiative)

Relevant documents

Human chromosome 17

Human chromosome 17: entries, gene names and cross-references to MIM

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

MIM cross-references

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

Human and mouse protein kinases

Human and mouse protein kinases: classification and index

SIMILARITY comments

Index of protein domains and families

Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Binary interactions · Alternative products · Sequence annotation (Features) · Sequences · References · Cross-references · Entry information · Relevant documents