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Q9DC28 (KC1D_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 106. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (4) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·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
OrganismMus musculus (Mouse) [Reference proteome]
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus

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.5 Ref.6 Ref.8 Ref.9 Ref.10 Ref.11 Ref.12

Catalytic activity

ATP + a protein = ADP + a phosphoprotein. Ref.8

ATP + [tau protein] = ADP + [tau protein] phosphate. Ref.8

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 By similarity.

Subunit structure

Binds to MAP1A. 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, DBNDD2, AIB1/NCOA3 and ESR1. AKAP9/AKAP450 binding promotes centrosomal subcellular location. Binds to tubulins in mitotic cells upon DNA damage By similarity. Binds to SNAPIN and DNMT1. Ref.3 Ref.6 Ref.8 Ref.10

Subcellular location

Cytoplasm By similarity. Nucleus. Cytoplasmcytoskeletonmicrotubule organizing centercentrosome By similarity. Cytoplasmperinuclear region By similarity. Cell membrane By similarity. Cytoplasmcytoskeletonspindle By similarity. Golgi apparatus By similarity. 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 By similarity. Ref.3 Ref.6 Ref.8

Tissue specificity

Expressed ubiquitously. However, kinase activity is not uniform, with highest kinase activity in splenocytes. Ref.4

Post-translational modification

Autophosphorylated on serine and threonine residues; this autophosphorylation represses activity. Reactivated by phosphatase-mediated dephosphorylation By similarity.

Disruption phenotype

Lethal. There are fewer embryos than expected at late stages of gestation; they weigh about 30% less than control animals, but appear otherwise normal. Mice die shortly after birth. Tissue-specific disruption increases the half-life of PER2 protein and alters circadian protein expression dynamics. Ref.8 Ref.9

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

Inferred from electronic annotation. Source: UniProtKB-KW

circadian regulation of gene expression

Inferred from mutant phenotype Ref.8. Source: UniProtKB

positive regulation of canonical Wnt signaling pathway

Inferred from electronic annotation. Source: Ensembl

positive regulation of proteasomal ubiquitin-dependent protein catabolic process

Inferred from mutant phenotype Ref.8. Source: UniProtKB

positive regulation of protein phosphorylation

Inferred from electronic annotation. Source: Ensembl

protein phosphorylation

Inferred from direct assay Ref.8. Source: UniProtKB

regulation of circadian rhythm

Inferred from mutant phenotype Ref.8. Source: UniProtKB

spindle assembly

Inferred from electronic annotation. Source: Ensembl

   Cellular_componentGolgi apparatus

Inferred from electronic annotation. Source: UniProtKB-SubCell

centrosome

Inferred from electronic annotation. Source: Ensembl

cytosol

Traceable author statement. Source: Reactome

nucleoplasm

Traceable author statement. Source: Reactome

nucleus

Inferred from direct assay Ref.8. Source: UniProtKB

perinuclear region of cytoplasm

Inferred from electronic annotation. Source: UniProtKB-SubCell

plasma membrane

Inferred from electronic annotation. Source: UniProtKB-SubCell

spindle microtubule

Inferred from electronic annotation. Source: Ensembl

   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.8. 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...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: Q9DC28-1)

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: Q9DC28-2)

The sequence of this isoform differs from the canonical sequence as follows:
     400-415: IPGRVASSGLQSVVHR → NSIPFEHHGK
Note: Contains a phosphoserine at position 401 (By similarity).

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 415415Casein kinase I isoform delta
PRO_0000192834

Regions

Domain9 – 277269Protein kinase
Nucleotide binding15 – 239ATP By similarity
Region278 – 36487Centrosomal localization signal (CLS) By similarity
Region317 – 34226Autoinhibitory By similarity

Sites

Active site1281Proton acceptor By similarity
Binding site381ATP By similarity

Amino acid modifications

Modified residue3311Phosphoserine By similarity
Modified residue3701Phosphoserine By similarity
Modified residue3821Phosphoserine Ref.7
Modified residue3831Phosphoserine By similarity
Modified residue3841Phosphoserine By similarity
Modified residue4111Phosphoserine By similarity

Natural variations

Alternative sequence400 – 41516IPGRV…SVVHR → NSIPFEHHGK in isoform 2.
VSP_010254

Experimental info

Mutagenesis441T → A: Increases pain sensitivity; reduces threshold for induction of cortical spreading depression; increases arterial dilation during cortical spreading depression and increases spontaneous and evoked calcium signaling in astrocytes. Ref.13
Sequence conflict3131E → G in BAB23405. Ref.1

Secondary structure

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

Details...

Sequences

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

Last modified May 10, 2004. Version 2.
Checksum: B97F04AF9EB466D2

FASTA41547,316
        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 VSSSDLTGRQ DTSRMSTSQI PGRVASSGLQ SVVHR 

« Hide

Isoform 2 [UniParc].

Checksum: 970B55B1B19AB9DD
Show »

FASTA40946,818

References

« Hide 'large scale' references
[1]"The transcriptional landscape of the mammalian genome."
Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J. expand/collapse author list , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.
Science 309:1559-1563(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
Strain: C57BL/6J and NOD.
Tissue: Bone marrow, Lung and Thymus.
[2]"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] (ISOFORM 1).
[3]"Nuclear entry of the circadian regulator mPER1 is controlled by mammalian casein kinase I epsilon."
Vielhaber E., Eide E., Rivers A., Gao Z.-H., Virshup D.M.
Mol. Cell. Biol. 20:4888-4899(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH PER1, SUBCELLULAR LOCATION.
[4]"Casein kinase I delta (CKIdelta) is involved in lymphocyte physiology."
Maritzen T., Loehler J., Deppert W., Knippschild U.
Eur. J. Cell Biol. 82:369-378(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: TISSUE SPECIFICITY.
[5]"Physiological role for casein kinase 1 in glutamatergic synaptic transmission."
Chergui K., Svenningsson P., Greengard P.
J. Neurosci. 25:6601-6609(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN SYNAPTIC TRANSMISSION.
[6]"Casein kinase 1 delta (CK1delta) interacts with the SNARE associated protein snapin."
Wolff S., Stoeter M., Giamas G., Piesche M., Henne-Bruns D., Banting G., Knippschild U.
FEBS Lett. 580:6477-6484(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION AS SNAPIN KINASE, SUBCELLULAR LOCATION, INTERACTION WITH SNAPIN.
[7]"Large-scale phosphorylation analysis of mouse liver."
Villen J., Beausoleil S.A., Gerber S.A., Gygi S.P.
Proc. Natl. Acad. Sci. U.S.A. 104:1488-1493(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-382, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Liver.
[8]"Casein kinase 1 delta regulates the pace of the mammalian circadian clock."
Etchegaray J.P., Machida K.K., Noton E., Constance C.M., Dallmann R., Di Napoli M.N., DeBruyne J.P., Lambert C.M., Yu E.A., Reppert S.M., Weaver D.R.
Mol. Cell. Biol. 29:3853-3866(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: DISRUPTION PHENOTYPE, INTERACTION WITH PER1 AND PER2, CATALYTIC ACTIVITY, SUBCELLULAR LOCATION, FUNCTION.
[9]"Essential roles of CKIdelta and CKIepsilon in the mammalian circadian clock."
Lee H., Chen R., Lee Y., Yoo S., Lee C.
Proc. Natl. Acad. Sci. U.S.A. 106:21359-21364(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN CIRCADIAN CLOCK, DISRUPTION PHENOTYPE.
[10]"The DNA-binding activity of mouse DNA methyltransferase 1 is regulated by phosphorylation with casein kinase 1delta/epsilon."
Sugiyama Y., Hatano N., Sueyoshi N., Suetake I., Tajima S., Kinoshita E., Kinoshita-Kikuta E., Koike T., Kameshita I.
Biochem. J. 427:489-497(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION AS DNMT1 KINASE, INTERACTION WITH DNMT1.
[11]"Casein kinase 1 delta (CK1delta) regulates period length of the mouse suprachiasmatic circadian clock in vitro."
Etchegaray J.-P., Yu E.A., Indic P., Dallmann R., Weaver D.R.
PLoS ONE 5:E10303-E10303(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN CIRCADIAN CLOCK.
[12]"Forebrain overexpression of CK1delta leads to down-regulation of dopamine receptors and altered locomotor activity reminiscent of ADHD."
Zhou M., Rebholz H., Brocia C., Warner-Schmidt J.L., Fienberg A.A., Nairn A.C., Greengard P., Flajolet M.
Proc. Natl. Acad. Sci. U.S.A. 107:4401-4406(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN DOPAMINE RECEPTORS.
[13]"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: MUTAGENESIS OF THR-44.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AK004606 mRNA. Translation: BAB23405.1.
AK088642 mRNA. Translation: BAC40472.1.
AK152721 mRNA. Translation: BAE31444.1.
AK157812 mRNA. Translation: BAE34206.1.
BC004604 mRNA. Translation: AAH04604.1.
PIRS47616.
RefSeqNP_620690.1. NM_139059.2.
UniGeneMm.216227.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
4JJRX-ray2.41A/B1-299[»]
ProteinModelPortalQ9DC28.
SMRQ9DC28. Positions 3-294.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid222545. 4 interactions.
DIPDIP-47809N.
IntActQ9DC28. 3 interactions.
STRING10090.ENSMUSP00000094305.

Chemistry

BindingDBQ9DC28.

PTM databases

PhosphoSiteQ9DC28.

Proteomic databases

PaxDbQ9DC28.
PRIDEQ9DC28.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSMUST00000018274; ENSMUSP00000018274; ENSMUSG00000025162. [Q9DC28-1]
ENSMUST00000070575; ENSMUSP00000070721; ENSMUSG00000025162. [Q9DC28-2]
GeneID104318.
KEGGmmu:104318.
UCSCuc007mvb.1. mouse. [Q9DC28-1]

Organism-specific databases

CTD1453.
MGIMGI:1355272. Csnk1d.

Phylogenomic databases

eggNOGCOG0515.
GeneTreeENSGT00730000110518.
HOGENOMHOG000182055.
HOVERGENHBG000176.
KOK08959.
OMAHMESSRR.
OrthoDBEOG7CZK5W.
TreeFamTF300544.

Enzyme and pathway databases

ReactomeREACT_109335. Circadian Clock.
REACT_24972. Circadian Clock.

Gene expression databases

ArrayExpressQ9DC28.
BgeeQ9DC28.
CleanExMM_CSNK1D.
GenevestigatorQ9DC28.

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. mouse.
NextBio356922.
PROQ9DC28.
SOURCESearch...

Entry information

Entry nameKC1D_MOUSE
AccessionPrimary (citable) accession number: Q9DC28
Secondary accession number(s): Q3TZK2, Q99KK4
Entry history
Integrated into UniProtKB/Swiss-Prot: May 10, 2004
Last sequence update: May 10, 2004
Last modified: April 16, 2014
This is version 106 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

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

MGD cross-references

Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot