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Q06486 (KC1D_RAT) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 127. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (2) | 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
EC=2.7.11.1
Alternative name(s):
Tau-protein kinase CSNK1D
EC=2.7.11.26
Gene names
Name:Csnk1d
Synonyms:Hckid
OrganismRattus norvegicus (Rat) [Reference proteome]
Taxonomic identifier10116 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus

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 By similarity. Ref.5

Catalytic activity

ATP + a protein = ADP + a phosphoprotein.

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

Enzyme regulation

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. Exhibits substrate-dependent heparin activation.

Subunit structure

Binds to DNMT1. 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 By similarity. Binds to MAP1A. Ref.5

Subcellular location

Cytoplasm By similarity. Nucleus By similarity. 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.

Tissue specificity

Expressed in most tissues, including heart, brain, testis, kidney, spleen and lung. Ref.4

Domain

The autoinhibitory domain is involved in regulating enzyme activity through autophosphorylation and possibly, through heparin binding. Ref.3

Post-translational modification

Autophosphorylated on serine and threonine residues; this autophosphorylation represses activity. Reactivated by phosphatase-mediated dephosphorylation. Ref.3 Ref.6

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
Direct protein sequencing
Reference proteome
Gene Ontology (GO)
   Biological_processWnt 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 PubMed 12270714. Source: RGD

positive regulation of canonical Wnt signaling pathway

Inferred from electronic annotation. Source: Ensembl

positive regulation of proteasomal ubiquitin-dependent protein catabolic process

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of protein phosphorylation

Inferred from electronic annotation. Source: Ensembl

protein phosphorylation

Inferred from sequence or structural similarity. Source: UniProtKB

regulation of circadian rhythm

Inferred from sequence or structural similarity. Source: UniProtKB

spindle assembly

Inferred from electronic annotation. Source: Ensembl

   Cellular_componentGolgi apparatus

Inferred from electronic annotation. Source: UniProtKB-SubCell

centrosome

Traceable author statement PubMed 12270714. Source: RGD

nucleus

Inferred from sequence or structural similarity. Source: UniProtKB

perinuclear region of cytoplasm

Inferred from electronic annotation. Source: UniProtKB-SubCell

plasma membrane

Inferred from electronic annotation. Source: UniProtKB-SubCell

spindle

Traceable author statement PubMed 12270714. Source: RGD

spindle microtubule

Inferred from electronic annotation. Source: Ensembl

   Molecular_functionATP binding

Inferred from direct assay Ref.1. Source: RGD

glycoprotein binding

Inferred from direct assay Ref.1. Source: RGD

peptide binding

Inferred from direct assay Ref.1. Source: RGD

phosphoprotein binding

Inferred from direct assay Ref.1. Source: RGD

protein kinase activity

Inferred from sequence or structural similarity. Source: UniProtKB

protein serine/threonine kinase activity

Inferred from direct assay Ref.1. Source: RGD

tau-protein kinase activity

Inferred from electronic annotation. Source: UniProtKB-EC

Complete GO annotation...

Binary interactions

With

Entry

#Exp.

IntAct

Notes

MDM2Q009872EBI-2910316,EBI-389668From a different organism.
SnapinQ9Z2664EBI-7088890,EBI-6170320From a different organism.

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: Q06486-1)

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: Q06486-2)

The sequence of this isoform differs from the canonical sequence as follows:
     400-415: IPGRVASSGLQSVVHR → RSRDMASLRLHAARQGARCRPQRPRRTTY

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 415415Casein kinase I isoform delta
PRO_0000192836

Regions

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

Sites

Active site1281Proton acceptor
Binding site381ATP By similarity

Amino acid modifications

Modified residue3311Phosphoserine By similarity
Modified residue3701Phosphoserine; by PKA Ref.6
Modified residue3821Phosphoserine By similarity
Modified residue3831Phosphoserine By similarity
Modified residue3841Phosphoserine By similarity
Modified residue4111Phosphoserine By similarity

Natural variations

Alternative sequence400 – 41516IPGRV…SVVHR → RSRDMASLRLHAARQGARCR PQRPRRTTY in isoform 2.
VSP_010255

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: E6B11915C1746568
Show »

FASTA42849,121

References

[1]"Molecular cloning, expression, and characterization of a 49-kilodalton casein kinase I isoform from rat testis."
Graves P.R., Haas D.W., Hagedorn C.H., Depaoli-Roach A.A., Roach P.J.
J. Biol. Chem. 268:6394-6401(1993) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), PROTEIN SEQUENCE OF 1-6.
Tissue: Testis.
[2]"Casein kinase 1 delta rat."
Takano A., Nagai K.
Submitted (JUN-2001) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
[3]"Role of COOH-terminal phosphorylation in the regulation of casein kinase I delta."
Graves P.R., Roach P.J.
J. Biol. Chem. 270:21689-21694(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: AUTOPHOSPHORYLATION, AUTOINHIBITORY DOMAIN.
[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] [Europe PMC] [Abstract]
Cited for: TISSUE SPECIFICITY.
[5]"Interaction of casein kinase 1 delta (CK1 delta) with the light chain LC2 of microtubule associated protein 1A (MAP1A)."
Wolff S., Xiao Z., Wittau M., Suessner N., Stoeter M., Knippschild U.
Biochim. Biophys. Acta 1745:196-206(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION AS MAP1A KINASE, INTERACTION WITH MAP1A.
[6]"Phosphorylation of CK1delta: identification of Ser370 as the major phosphorylation site targeted by PKA in vitro and in vivo."
Giamas G., Hirner H., Shoshiashvili L., Grothey A., Gessert S., Kuehl M., Henne-Bruns D., Vorgias C.E., Knippschild U.
Biochem. J. 406:389-398(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION AT SER-370 BY PKA.
[7]"Three-dimensional structure of mammalian casein kinase I: molecular basis for phosphate recognition."
Longenecker K.L., Roach P.J., Hurley T.D.
J. Mol. Biol. 257:618-631(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS) OF 1-317.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
L07578 mRNA. Translation: AAA40934.1.
AB063114 mRNA. Translation: BAB60852.1.
PIRA46002.
RefSeqNP_620691.2. NM_139060.3.
UniGeneRn.8046.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1CKIX-ray2.30A/B1-317[»]
1CKJX-ray2.46A/B1-317[»]
ProteinModelPortalQ06486.
SMRQ06486. Positions 3-294.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid249077. 5 interactions.
IntActQ06486. 11 interactions.
MINTMINT-3389660.
STRING10116.ENSRNOP00000015178.

Chemistry

BindingDBQ06486.
ChEMBLCHEMBL4484.

PTM databases

PhosphoSiteQ06486.

Proteomic databases

PRIDEQ06486.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSRNOT00000015178; ENSRNOP00000015178; ENSRNOG00000036676. [Q06486-2]
ENSRNOT00000054936; ENSRNOP00000051819; ENSRNOG00000036676. [Q06486-1]
GeneID64462.
KEGGrno:64462.

Organism-specific databases

CTD1453.
RGD71031. Csnk1d.

Phylogenomic databases

eggNOGCOG0515.
GeneTreeENSGT00730000110518.
HOGENOMHOG000182055.
HOVERGENHBG000176.
KOK08959.
OMANTREDQL.
OrthoDBEOG7CZK5W.
PhylomeDBQ06486.

Enzyme and pathway databases

BRENDA2.7.11.1. 5301.

Gene expression databases

GenevestigatorQ06486.

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

EvolutionaryTraceQ06486.
NextBio613212.
PROQ06486.

Entry information

Entry nameKC1D_RAT
AccessionPrimary (citable) accession number: Q06486
Secondary accession number(s): Q99KK4
Entry history
Integrated into UniProtKB/Swiss-Prot: June 1, 1994
Last sequence update: May 10, 2004
Last modified: April 16, 2014
This is version 127 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

PDB cross-references

Index of Protein Data Bank (PDB) cross-references