CSNK1D - Casein kinase I isoform delta - human protein (Function)
 
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CSNK1D »  Casein kinase I isoform delta   [ EC 2.7.11.1 ]  (CKId)
 
Protein also known as:  Tau-protein kinase CSNK1D [EC 2.7.11.26].
Gene name:  CSNK1D
Entry whose protein(s) existence is based on evidence at protein level
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GENE REF ISO

Function

 show evidences
Overview 
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.  
17
  • CuratedUniProtKB
GO molecular function 
ATP bindingdefinition[GO:0005524] silver  
  • IEAOrtholog Compara
Glycoprotein bindingdefinition[GO:0001948] silver  
  • IEAOrtholog Compara
Peptide bindingdefinition[GO:0042277] silver  
  • IEAOrtholog Compara
Phosphoprotein bindingdefinition[GO:0051219] silver  
  • IEAOrtholog Compara
Protein bindingdefinition[GO:0005515]  
3
  • IPIIntAct
  • IPIUniProtKB
Protein kinase activitydefinition[GO:0004672]  
2
  • IDAUniProtKB
  • ISSOrtholog Curator
Protein serine/threonine kinase activitydefinition[GO:0004674] silver  
  • IEAOrtholog Compara
Tau-protein kinase activitydefinition[GO:0050321]  
  • IEAEC 2 GO
GO biological process 
Circadian regulation of gene expressiondefinition[GO:0032922]  
  • ISSOrtholog Curator
DNA repairdefinition[GO:0006281]  
1
  • TASPINC
Positive regulation of canonical Wnt signaling pathwaydefinition[GO:0090263]  
1
  • IMPBHF-UCL
Positive regulation of proteasomal ubiquitin-dependent protein catabolic processdefinition[GO:0032436]  
  • ISSOrtholog Curator
Positive regulation of protein phosphorylationdefinition[GO:0001934]  
1
  • IMPBHF-UCL
Protein phosphorylationdefinition[GO:0006468]  
1
  • IDAUniProtKB
Regulation of circadian rhythmdefinition[GO:0042752]  
  • ISSOrtholog Curator
Signal transductiondefinition[GO:0007165]  
1
  • TASPINC
Spindle assemblydefinition[GO:0051225]  
1
  • IDAUniProtKB
Wnt signaling pathwaydefinition[GO:0016055]  
  • IEAUniProtKB KW
Enzymatic activity 
This protein acts as an enzyme. It is known to catalyze the following reactions
EC 2.7.11.1: ATP + a protein ADP + a phosphoprotein.  
2
  • CuratedUniProtKB
EC 2.7.11.26: ATP + [tau protein] ADP + [tau protein] phosphate.  
2
  • CuratedUniProtKB
It is regulated in the following manner
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).  
10
  • CuratedUniProtKB
 
More information is available from:
Pathways 
According to KEGG, this protein belongs to the following pathways:
Circadian rhythm - mammal  hsa04710+1453  
Gap junction  hsa04540+1453  
Hedgehog signaling pathway  hsa04340+1453  
According to Reactome, this protein belongs to the following pathways:
Cell Cycle  REACT_115566  
Circadian Clock  REACT_24941  
Note 
May be involved in Alzheimer disease by phosphorylating MAPT/TAU (PubMed17562708).  
1
  • CuratedUniProtKB
Caution 
Was shown to phosphorylate and activate DCK in vitro but probably not in vivo (PubMed20637175).  
1
  • CuratedUniProtKB
 

Biophysicochemical properties

Kinetic parameters
Maximal velocity nearly identical for the reactions with alpha-casein and PER2 peptide.
KM 36.5 uM for alpha-casein
KM 635.8 uM for PER2 peptide
KM 180.6 uM for ATP

Keywords

Biological process 
Biological rhythms  definition   [KW-0090]
Wnt signaling pathway  definition   [KW-0879]
Molecular function 
Kinase  definition   [KW-0418]
Serine/threonine-protein kinase  definition   [KW-0723]
Transferase  definition   [KW-0808]
Technical term 
Reference proteome  definition   [KW-1185]
 

Further external links

Other
GeneWiki: CSNK1D
GenomeRNAi: 1453
PRO: PR:P48730
Chemistry
GuidetoPHARMACOLOGY: 1997