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P48730 (KC1D_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 144. 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·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Casein kinase I isoform delta

Short name=CKI-delta
Short name=CKId
EC=2.7.11.1
Alternative name(s):
Tau-protein kinase CSNK1D
EC=2.7.11.26
Gene names
Name:CSNK1D
Synonyms:HCKID
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length415 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Essential serine/threonine-protein kinase that regulates diverse cellular growth and survival processes including Wnt signaling, DNA repair and circadian rhythms. It can phosphorylate a large number of proteins. Casein kinases are operationally defined by their preferential utilization of acidic proteins such as caseins as substrates. Phosphorylates connexin-43/GJA1, MAP1A, SNAPIN, MAPT/TAU, TOP2A, DCK, HIF1A, EIF6, p53/TP53, DVL2, DVL3, ESR1, AIB1/NCOA3, DNMT1, PKD2, YAP1, PER1 and PER2. Central component of the circadian clock. May act as a negative regulator of circadian rhythmicity by phosphorylating PER1 and PER2, leading to retain PER1 in the cytoplasm. YAP1 phosphorylation promotes its SCF(beta-TRCP) E3 ubiquitin ligase-mediated ubiquitination and subsequent degradation. DNMT1 phosphorylation reduces its DNA-binding activity. Phosphorylation of ESR1 and AIB1/NCOA3 stimulates their activity and coactivation. Phosphorylation of DVL2 and DVL3 regulates WNT3A signaling pathway that controls neurite outgrowth. EIF6 phosphorylation promotes its nuclear export. Triggers down-regulation of dopamine receptors in the forebrain. Activates DCK in vitro by phosphorylation. TOP2A phosphorylation favors DNA cleavable complex formation. May regulate the formation of the mitotic spindle apparatus in extravillous trophoblast. Modulates connexin-43/GJA1 gap junction assembly by phosphorylation. Probably involved in lymphocyte physiology. Regulates fast synaptic transmission mediated by glutamate. Ref.7 Ref.11 Ref.13 Ref.14 Ref.16 Ref.17 Ref.23 Ref.24 Ref.26 Ref.27 Ref.28 Ref.29 Ref.30 Ref.31 Ref.34 Ref.35 Ref.44

Catalytic activity

ATP + a protein = ADP + a phosphoprotein. Ref.15 Ref.44

ATP + [tau protein] = ADP + [tau protein] phosphate. Ref.15 Ref.44

Enzyme regulation

Exhibits substrate-dependent heparin activation. Drug-mediated inhibition leads to a delay of the oscillations with the magnitude of this effect dependent upon the timing of drug administration. Inhibited by phosphorylation. Repressed by 3-[(2,4,6-trimethoxyphenyl)methylidenyl]-indolin-2-one (IC261), N-(2-aminoethyl)-5-chloroisoquinoline-8-sulfonamide (CKI-7), 4-[4-(2,3-dihydro-benzo[1,4]dioxin-6-yl)-5-pyridin-2-yl-1H-imidazol-2-yl]benzamide (D4476), 3,4-diaryl-isoxazoles and -imidazoles, and 4-(3-cyclohexyl-5-(4-fluoro-phenyl)-3H-imidazol-4-yl) pyrimidin-2-ylamine (PF670462, PF670). Ref.6 Ref.13 Ref.14 Ref.21 Ref.23 Ref.30 Ref.31 Ref.34 Ref.35 Ref.36

Subunit structure

Binds to DNMT1 and MAP1A By similarity. 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 MAPT/TAU, SNAPIN, DBNDD2, AIB1/NCOA3 and ESR1. AKAP9/AKAP450 binding promotes centrosomal subcellular location. Binds to tubulins in mitotic cells upon DNA damage. Ref.8 Ref.10 Ref.11 Ref.12 Ref.13 Ref.15 Ref.24

Subcellular location

Cytoplasm. Nucleus. Cytoplasmcytoskeletonmicrotubule organizing centercentrosome. Cytoplasmperinuclear region. Cell membrane. Cytoplasmcytoskeletonspindle. Golgi apparatus. Note: Localized at mitotic spindle microtubules, and at the centrosomes and interphase in interphase cells. Recruited to the spindle apparatus and the centrosomes in response to DNA-damage. Correct subcellular localization requires kinase activity. Ref.8 Ref.9 Ref.12 Ref.14 Ref.35

Tissue specificity

Expressed in all tissues examined, including brain, heart, lung, liver, pancreas, kidney, placenta and skeletal muscle. However, kinase activity is not uniform, with highest kinase activity in splenocytes. In blood, highly expressed in hemopoietic cells and mature granulocytes. Also found in monocytes and lymphocytes. Ref.2 Ref.14

Developmental stage

Highly present in extravillous trophoblast cells, which are present at the placenta implantation site and invade the decidua and decidual vessels. Ref.14

Post-translational modification

Autophosphorylated on serine and threonine residues; this autophosphorylation represses activity. Reactivated by phosphatase-mediated dephosphorylation. Ref.6 Ref.36

Involvement in disease

Advanced sleep phase syndrome, familial, 2 (FASPS2) [MIM:615224]: A disorder characterized by very early sleep onset and offset. Individuals are 'morning larks' with a 4 hours advance of the sleep, temperature and melatonin rhythms.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.41 Ref.44

Miscellaneous

May be involved in Alzheimer disease by phosphorylating MAPT/TAU (Ref.17).

Sequence similarities

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

Contains 1 protein kinase domain.

Caution

Was shown to phosphorylate and activate DCK in vitro but probably not in vivo (Ref.26).

Biophysicochemical properties

Kinetic parameters:

Maximal velocity nearly identical for the reactions with alpha-casein and PER2 peptide.

KM=36.5 µM for alpha-casein Ref.44

KM=635.8 µM for PER2 peptide

KM=180.6 µM for ATP

Ontologies

Keywords
   Biological processBiological rhythms
Wnt signaling pathway
   Cellular componentCell membrane
Cytoplasm
Cytoskeleton
Golgi apparatus
Membrane
Nucleus
   Coding sequence diversityAlternative splicing
Polymorphism
   DiseaseDisease mutation
   LigandATP-binding
Nucleotide-binding
   Molecular functionKinase
Serine/threonine-protein kinase
Transferase
   PTMPhosphoprotein
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processDNA repair

Traceable author statement Ref.1. Source: ProtInc

G2/M transition of mitotic cell cycle

Traceable author statement. Source: Reactome

Wnt signaling pathway

Inferred from electronic annotation. Source: UniProtKB-KW

circadian regulation of gene expression

Inferred from sequence or structural similarity. Source: UniProtKB

mitotic cell cycle

Traceable author statement. Source: Reactome

positive regulation of canonical Wnt signaling pathway

Inferred from mutant phenotype PubMed 20412773. Source: BHF-UCL

positive regulation of proteasomal ubiquitin-dependent protein catabolic process

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of protein phosphorylation

Inferred from mutant phenotype PubMed 20412773. Source: BHF-UCL

protein phosphorylation

Inferred from direct assay Ref.15. Source: UniProtKB

regulation of circadian rhythm

Inferred from sequence or structural similarity. Source: UniProtKB

signal transduction

Traceable author statement Ref.1. Source: ProtInc

spindle assembly

Inferred from direct assay Ref.8. Source: UniProtKB

   Cellular_componentGolgi apparatus

Inferred from direct assay Ref.8. Source: UniProtKB

centrosome

Inferred from direct assay PubMed 21399614Ref.35. Source: UniProtKB

cytosol

Traceable author statement. Source: Reactome

nucleus

Inferred from sequence or structural similarity. Source: UniProtKB

perinuclear region of cytoplasm

Inferred from direct assay Ref.14. Source: UniProtKB

plasma membrane

Inferred from direct assay Ref.14. Source: UniProtKB

spindle

Inferred from direct assay Ref.8. Source: UniProtKB

spindle microtubule

Inferred from direct assay Ref.8. Source: UniProtKB

   Molecular_functionATP binding

Inferred from electronic annotation. Source: UniProtKB-KW

peptide binding

Inferred from electronic annotation. Source: Ensembl

protein kinase activity

Inferred from direct assay Ref.15. Source: UniProtKB

protein serine/threonine kinase activity

Inferred from electronic annotation. Source: UniProtKB-KW

tau-protein kinase activity

Inferred from electronic annotation. Source: UniProtKB-EC

Complete GO annotation...

Binary interactions

With

Entry

#Exp.

IntAct

Notes

Dvl2Q608382EBI-751621,EBI-641940From a different organism.
MDM2Q009876EBI-751621,EBI-389668

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

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
Region278 – 36487Centrosomal localization signal (CLS)
Region317 – 34226Autoinhibitory By similarity

Sites

Active site1281Proton acceptor By similarity
Binding site381ATP By similarity

Amino acid modifications

Modified residue3311Phosphoserine Ref.20
Modified residue3701Phosphoserine By similarity
Modified residue3821Phosphoserine By similarity
Modified residue3831Phosphoserine Ref.25
Modified residue3841Phosphoserine Ref.20
Modified residue4111Phosphoserine Ref.22

Natural variations

Alternative sequence400 – 41516IPGRV…SVVHR → NSIPFEHHGK in isoform 2.
VSP_010253
Natural variant441T → A in FASPS2; strongly reduces kinase activity. Ref.41 Ref.44
VAR_029075
Natural variant461H → R in FASPS2; strongly reduces kinase activity. Ref.44
VAR_069801
Natural variant971S → C in breast cancer samples; infiltrating ductal carcinoma; somatic mutation. Ref.42 Ref.43
VAR_036451
Natural variant4011P → A. Ref.43
Corresponds to variant rs56124628 [ dbSNP | Ensembl ].
VAR_042081

Experimental info

Mutagenesis381K → M: Impaired kinase activity and abnormal subcellular localization with exclusive accumulation to the nucleus. Ref.9
Mutagenesis1761T → I: Impaired kinase activity and abnormal subcellular localization with exclusive accumulation to the nucleus. Ref.9
Sequence conflict3301A → D in AAC50807. Ref.1

Secondary structure

................................................. 415
Helix Strand Turn

Details...

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 [UniParc].

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] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [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] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), TISSUE SPECIFICITY.
Tissue: Hematopoietic stem cell.
[3]NHLBI resequencing and genotyping service (RS&G)
Submitted (SEP-2006) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[4]"Complete sequencing and characterization of 21,243 full-length human cDNAs."
Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. expand/collapse author list , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
Tissue: Placenta.
[5]"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] (ISOFORMS 1 AND 2).
Tissue: Placenta and Spleen.
[6]"Regulation of casein kinase I epsilon and casein kinase I delta by an in vivo futile phosphorylation cycle."
Rivers A., Gietzen K.F., Vielhaber E., Virshup D.M.
J. Biol. Chem. 273:15980-15984(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: ENZYME REGULATION, AUTOPHOSPHORYLATION.
[7]"Protein kinase CK1 is a p53-threonine 18 kinase which requires prior phosphorylation of serine 15."
Dumaz N., Milne D.M., Meek D.W.
FEBS Lett. 463:312-316(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION AS TP53 KINASE.
[8]"Interaction of casein kinase 1 delta (CK1delta) with post-Golgi structures, microtubules and the spindle apparatus."
Behrend L., Stoeter M., Kurth M., Rutter G., Heukeshoven J., Deppert W., Knippschild U.
Eur. J. Cell Biol. 79:240-251(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH TUBULINS, SUBCELLULAR LOCATION.
[9]"Catalytic activity of protein kinase CK1 delta (casein kinase 1delta) is essential for its normal subcellular localization."
Milne D.M., Looby P., Meek D.W.
Exp. Cell Res. 263:43-54(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: SUBCELLULAR LOCATION, MUTAGENESIS OF LYS-38 AND THR-176.
[10]"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] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH PER1 AND PER2.
[11]"Casein kinase 1 regulates connexin-43 gap junction assembly."
Cooper C.D., Lampe P.D.
J. Biol. Chem. 277:44962-44968(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION AS CONNEXIN-43/GJA1 KINASE, INTERACTION WITH CONNEXIN-43/GJA1.
[12]"Centrosomal anchoring of the protein kinase CK1delta mediated by attachment to the large, coiled-coil scaffolding protein CG-NAP/AKAP450."
Sillibourne J.E., Milne D.M., Takahashi M., Ono Y., Meek D.W.
J. Mol. Biol. 322:785-797(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH AKAP9/AKAP450, SUBCELLULAR LOCATION.
[13]"Casein kinase 1 delta phosphorylates tau and disrupts its binding to microtubules."
Li G., Yin H., Kuret J.
J. Biol. Chem. 279:15938-15945(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION AS MAPT/TAU KINASE, ENZYME REGULATION, INTERACTION WITH MAPT/TAU.
[14]"Inhibition of casein kinase I delta alters mitotic spindle formation and induces apoptosis in trophoblast cells."
Stoeter M., Bamberger A.-M., Aslan B., Kurth M., Speidel D., Loening T., Frank H.-G., Kaufmann P., Loehler J., Henne-Bruns D., Deppert W., Knippschild U.
Oncogene 24:7964-7975(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN MITOTIC SPINDLE FORMATION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, DEVELOPMENTAL STAGE, ENZYME REGULATION.
[15]"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: CATALYTIC ACTIVITY, INTERACTION WITH DBNDD2.
[16]"Phosphorylation at Ser244 by CK1 determines nuclear localization and substrate targeting of PKD2."
von Blume J., Knippschild U., Dequiedt F., Giamas G., Beck A., Auer A., Van Lint J., Adler G., Seufferlein T.
EMBO J. 26:4619-4633(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION AS PKD2 KINASE.
[17]"Novel phosphorylation sites in tau from Alzheimer brain support a role for casein kinase 1 in disease pathogenesis."
Hanger D.P., Byers H.L., Wray S., Leung K.-Y., Saxton M.J., Seereeram A., Reynolds C.H., Ward M.A., Anderton B.H.
J. Biol. Chem. 282:23645-23654(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION AS MAPT/TAU KINASE.
[18]"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] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[19]"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: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[20]"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-331 AND SER-384, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[21]"3,4-Diaryl-isoxazoles and -imidazoles as potent dual inhibitors of p38alpha mitogen activated protein kinase and casein kinase 1delta."
Peifer C., Abadleh M., Bischof J., Hauser D., Schattel V., Hirner H., Knippschild U., Laufer S.
J. Med. Chem. 52:7618-7630(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: ENZYME REGULATION.
[22]"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-411, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[23]"Casein kinase I delta/epsilon phosphorylates topoisomerase IIalpha at serine-1106 and modulates DNA cleavage activity."
Grozav A.G., Chikamori K., Kozuki T., Grabowski D.R., Bukowski R.M., Willard B., Kinter M., Andersen A.H., Ganapathi R., Ganapathi M.K.
Nucleic Acids Res. 37:382-392(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION AS TOP2A KINASE, ENZYME REGULATION.
[24]"CK1delta modulates the transcriptional activity of ERalpha via AIB1 in an estrogen-dependent manner and regulates ERalpha-AIB1 interactions."
Giamas G., Castellano L., Feng Q., Knippschild U., Jacob J., Thomas R.S., Coombes R.C., Smith C.L., Jiao L.R., Stebbing J.
Nucleic Acids Res. 37:3110-3123(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION AS AIB1/NCOA3 AND ESR1 KINASE, INTERACTION WITH AIB1/NCOA3 AND ESR1.
[25]"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-383, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Leukemic T-cell.
[26]"Casein kinase 1delta activates human recombinant deoxycytidine kinase by Ser-74 phosphorylation, but is not involved in the in vivo regulation of its activity."
Smal C., Vertommen D., Amsailale R., Arts A., Degand H., Morsomme P., Rider M.H., Neste E.V., Bontemps F.
Arch. Biochem. Biophys. 502:44-52(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION AS DCK KINASE.
[27]"Isoform specific phosphorylation of p53 by protein kinase CK1."
Venerando A., Marin O., Cozza G., Bustos V.H., Sarno S., Pinna L.A.
Cell. Mol. Life Sci. 67:1105-1118(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION AS P53/TP53 KINASE, GENE FAMILY.
[28]"A coordinated phosphorylation by Lats and CK1 regulates YAP stability through SCF(beta-TRCP)."
Zhao B., Li L., Tumaneng K., Wang C.-Y., Guan K.-L.
Genes Dev. 24:72-85(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION AS YAP1 KINASE.
[29]"Casein kinase 1 regulates human hypoxia-inducible factor HIF-1."
Kalousi A., Mylonis I., Politou A.S., Chachami G., Paraskeva E., Simos G.
J. Cell Sci. 123:2976-2986(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION AS HIF1A KINASE.
[30]"Entrainment of disrupted circadian behavior through inhibition of casein kinase 1 (CK1) enzymes."
Meng Q.-J., Maywood E.S., Bechtold D.A., Lu W.-Q., Li J., Gibbs J.E., Dupre S.M., Chesham J.E., Rajamohan F., Knafels J., Sneed B., Zawadzke L.E., Ohren J.F., Walton K.M., Wager T.T., Hastings M.H., Loudon A.S.I.
Proc. Natl. Acad. Sci. U.S.A. 107:15240-15245(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN CIRCADIAN RHYTHMS, ENZYME REGULATION.
[31]"Chronic treatment with a selective inhibitor of casein kinase I delta/epsilon yields cumulative phase delays in circadian rhythms."
Sprouse J., Reynolds L., Kleiman R., Tate B., Swanson T.A., Pickard G.E.
Psychopharmacology 210:569-576(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN CIRCADIAN RHYTHMS, ENZYME REGULATION.
[32]"Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis."
Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.
Sci. Signal. 3:RA3-RA3(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[33]"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].
[34]"Opposing action of casein kinase 1 and calcineurin in nucleo-cytoplasmic shuttling of mammalian translation initiation factor eIF6."
Biswas A., Mukherjee S., Das S., Shields D., Chow C.W., Maitra U.
J. Biol. Chem. 286:3129-3138(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION AS EIF6 KINASE, ENZYME REGULATION.
[35]"Casein kinase 1 delta functions at the centrosome to mediate Wnt-3a-dependent neurite outgrowth."
Greer Y.E., Rubin J.S.
J. Cell Biol. 192:993-1004(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION AS DVL2 AND DVL3 KINASE, ENZYME REGULATION, SUBCELLULAR LOCATION.
[36]"IC261 induces cell cycle arrest and apoptosis of human cancer cells via CK1delta/epsilon and Wnt/beta-catenin independent inhibition of mitotic spindle formation."
Cheong J.K., Nguyen T.H., Wang H., Tan P., Voorhoeve P.M., Lee S.H., Virshup D.M.
Oncogene 30:2558-2569(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: ENZYME REGULATION, AUTOPHOSPHORYLATION.
[37]"Casein kinase 1: Complexity in the family."
Cheong J.K., Virshup D.M.
Int. J. Biochem. Cell Biol. 43:465-469(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: REVIEW ON CIRCADIAN RHYTHMS, GENE FAMILY.
[38]"Crystallographic studies of casein kinase I delta toward a structural understanding of auto-inhibition."
Longenecker K.L., Roach P.J., Hurley T.D.
Acta Crystallogr. D 54:473-475(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.4 ANGSTROMS).
[39]"Structural basis for the interaction between casein kinase 1 delta and a potent and selective inhibitor."
Long A., Zhao H., Huang X.
J. Med. Chem. 55:956-960(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (1.94 ANGSTROMS) OF 1-294 IN COMPLEX WITH INHIBITOR.
[40]"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 (2.07 ANGSTROMS) OF 1-294 IN COMPLEX WITH INHIBITOR.
[41]"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] [Europe PMC] [Abstract]
Cited for: VARIANT FASPS2 ALA-44.
[42]"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] [Europe PMC] [Abstract]
Cited for: VARIANT [LARGE SCALE ANALYSIS] CYS-97.
[43]"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] CYS-97 AND ALA-401.
[44]"Casein kinase idelta mutations in familial migraine and advanced phase."
Brennan K.C., Bates E.A., Shapiro R.E., Zyuzin J., Hallows W.C., Huang Y., Lee H.Y., Jones C.R., Fu Y.H., Charles A.C., Ptacek L.J.
Sci. Transl. Med. 5:183ra56-183ra56(2013) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS FASPS2 ALA-44 AND ARG-46, CHARACTERIZATION OF VARIANTS FASPS2 ALA-44 AND ARG-46, FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
U29171 mRNA. Translation: AAC50807.1.
U31285 mRNA. Translation: AAC50808.1.
AB091044 mRNA. Translation: BAC10903.1.
AK291758 mRNA. Translation: BAF84447.1.
EF015900 Genomic DNA. Translation: ABM64211.1.
BC003558 mRNA. Translation: AAH03558.1.
BC015775 mRNA. Translation: AAH15775.1.
PIRG01876.
RefSeqNP_001884.2. NM_001893.4.
NP_620693.1. NM_139062.2.
UniGeneHs.631725.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
3UYSX-ray2.30A/B/C/D1-294[»]
3UYTX-ray2.00A/B/C/D1-294[»]
3UZPX-ray1.94A/B1-294[»]
4HGTX-ray1.80A/B1-294[»]
4HNFX-ray2.07A/B1-294[»]
4KB8X-ray1.95A/B/C/D3-317[»]
4KBAX-ray1.98A/B/C/D3-317[»]
4KBCX-ray1.98A/B1-317[»]
4KBKX-ray2.10A/B/C/D3-317[»]
ProteinModelPortalP48730.
SMRP48730. Positions 3-294.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid107837. 32 interactions.
DIPDIP-39735N.
IntActP48730. 12 interactions.
MINTMINT-1454355.
STRING9606.ENSP00000324464.

Chemistry

BindingDBP48730.
ChEMBLCHEMBL2828.
GuidetoPHARMACOLOGY1997.

PTM databases

PhosphoSiteP48730.

Polymorphism databases

DMDM27923980.

Proteomic databases

PaxDbP48730.
PRIDEP48730.

Protocols and materials databases

DNASU1453.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000314028; ENSP00000324464; ENSG00000141551. [P48730-1]
ENST00000392334; ENSP00000376146; ENSG00000141551. [P48730-2]
GeneID1453.
KEGGhsa:1453.
UCSCuc002kei.3. human. [P48730-2]
uc002kej.3. human. [P48730-1]

Organism-specific databases

CTD1453.
GeneCardsGC17M080203.
HGNCHGNC:2452. CSNK1D.
HPACAB015410.
MIM600864. gene.
615224. phenotype.
neXtProtNX_P48730.
Orphanet164736. Familial advanced sleep-phase syndrome.
PharmGKBPA26952.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG0515.
HOGENOMHOG000182055.
HOVERGENHBG000176.
InParanoidP48730.
KOK08959.
PhylomeDBP48730.
TreeFamTF300544.

Enzyme and pathway databases

BRENDA2.7.11.1. 2681.
ReactomeREACT_115566. Cell Cycle.
REACT_24941. Circadian Clock.
SignaLinkP48730.

Gene expression databases

ArrayExpressP48730.
BgeeP48730.
CleanExHS_CSNK1D.
GenevestigatorP48730.

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

ChiTaRSCSNK1D. human.
GeneWikiCSNK1D.
GenomeRNAi1453.
NextBio5961.
PROP48730.
SOURCESearch...

Entry information

Entry nameKC1D_HUMAN
AccessionPrimary (citable) accession number: P48730
Secondary accession number(s): A2I2P2, Q96KZ6, Q9BTN5
Entry history
Integrated into UniProtKB/Swiss-Prot: February 1, 1996
Last sequence update: January 27, 2003
Last modified: April 16, 2014
This is version 144 of the entry and version 2 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 17

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