Reviewed, UniProtKB/Swiss-Prot P48730 (KC1D_HUMAN)

Names and origin

Protein names

Recommended name:
    Casein kinase I isoform delta
      Short name=CKI-delta
      Short name=CKId
    EC=2.7.11.1

Gene names

Name:

CSNK1D

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	415 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. 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

Keywords
Biological process	Wnt signaling pathway
Cellular component	Cytoplasm
Coding sequence diversity	Alternative splicing Polymorphism
Disease	Disease mutation
Ligand	ATP-binding Nucleotide-binding
Molecular function	Kinase Serine/threonine-protein kinase Transferase
PTM	Phosphoprotein
Gene Ontology (GO)
Biological process	DNA repair Ref.1 Traceable author statement. Source: ProtInc Wnt receptor signaling pathway Inferred from electronic annotation. Source: UniProtKB-KW protein amino acid phosphorylation Ref.1 Traceable author statement. Source: ProtInc
Cellular component	cytoplasm Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW protein binding Inferred from physical interaction. Source: IntAct protein serine/threonine kinase activity Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
MCC	P23508	1	EBI-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 key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 415	415	Casein kinase I isoform delta		PRO_0000192833
Regions
	Domain	9 – 277	269	Protein kinase
	Nucleotide binding	15 – 23	9	ATP By similarity
	Region	317 – 342	26	Autoinhibitory By similarity
Sites
	Active site	128	1	Proton acceptor By similarity
	Binding site	38	1	ATP By similarity
Amino acid modifications
	Modified residue	328	1	Phosphoserine Ref.8
	Modified residue	331	1	Phosphoserine Ref.8 Ref.6 Ref.9
	Modified residue	347	1	Phosphothreonine Ref.8 Ref.9
	Modified residue	349	1	Phosphothreonine Ref.9
	Modified residue	350	1	Phosphoserine Ref.8 Ref.5
	Modified residue	382	1	Phosphoserine Ref.8 Ref.6 Ref.9
	Modified residue	383	1	Phosphoserine Ref.8 Ref.7
	Modified residue	384	1	Phosphoserine Ref.8 Ref.9
	Modified residue	387	1	Phosphothreonine Ref.8
	Modified residue	396	1	Phosphoserine Ref.8
	Modified residue	397	1	Phosphothreonine Ref.8
	Modified residue	398	1	Phosphoserine Ref.8
	Modified residue	406	1	Phosphoserine Ref.8
	Modified residue	407	1	Phosphoserine Ref.8
Natural variations
	Alternative sequence	400 – 415	16	IPGRV…SVVHR → NSIPFEHHGK in isoform 2.		VSP_010253
	Natural variant	44	1	T → A in FASPS. Ref.11		VAR_029075
	Natural variant	97	1	S → C in breast cancer samples; infiltrating ductal carcinoma; somatic mutation. Ref.12 Ref.13		VAR_036451
	Natural variant	401	1	P → A Ref.13		VAR_042081
Experimental info
	Sequence conflict	330	1	A → D in AAC50807. Ref.1

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified January 27, 2003. Version 2. Checksum: B97F1717A52466D2	FASTA	415	47,330
	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
	Isoform 2. Checksum: 970B55B1AF6B56DD	FASTA	409	46,832
	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 SGMERERKVS MRLHRGAPVN ISSSDLTGRQ DTSRMSTSQN SIPFEHHGK

References

	« Hide 'large scale' referencesShow '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. , 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. , 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
EMBLGenBankDDBJ	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.
IPI	IPI00011102. IPI00234463.
PIR	G01876.
RefSeq	NP_001884.2. NP_620693.1.
UniGene	Hs.631725
3D structure databases
HSSP	HSSP built from PDB template 1CKJ based on UniProtKB Q06486.
SMR	P48730. Positions 1-296.
ModBase	Search...
Protein-protein interaction databases
IntAct	P48730. 7 interactions.
PTM databases
PhosphoSite	P48730.
Proteomic databases
PRIDE	P48730.
Genome annotation databases
Ensembl	ENSG00000141551. Homo sapiens. [Contig view]
GeneID	1453.
KEGG	hsa:1453.
Organism-specific databases
GeneCards	GC17M077795.
H-InvDB	HIX0014253.
HGNC	HGNC:2452. CSNK1D.
HPA	CAB015410.
MIM	600864. gene. 604348. phenotype.
Orphanet	164736. Advanced sleep-phase syndrome, familial.
PharmGKB	PA26952.
GenAtlas	Search...
Phylogenomic databases
HOGENOM	P48730.
HOVERGEN	P48730.
OMA	P48730. RMSTSQR.
Enzyme and pathway databases
BRENDA	2.7.11.1. 247.
Pathway_Interaction_DB	foxopathway. FoxO family signaling. hedgehog_glipathway. Hedgehog signaling events mediated by Gli proteins.
Gene expression databases
ArrayExpress	P48730.
Bgee	P48730.
CleanEx	HS_CSNK1D.
GermOnline	ENSG00000141551. Homo sapiens.
Family and domain databases
InterPro	IPR000719. Prot_kinase_core. IPR017441. Protein_kinase_ATP_BS. 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]
ProtoNet	Search...
Other Resources
NextBio	5961.
SOURCE	Search...

Entry information

Entry name

KC1D_HUMAN

Accession

Primary (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 status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)