InnateDB: Systems Biology of the Innate Immune Response

Homo sapiens Protein: CSNK1D

Summary

InnateDB Protein

IDBP-245870.7

Last Modified

2014-10-13 [Report errors or provide feedback]

Gene Symbol

CSNK1D

Protein Name

casein kinase 1, delta

Synonyms

ASPS; CKIdelta; FASPS2; HCKID;

Species

Homo sapiens

Ensembl Protein

ENSP00000376146

InnateDB Gene

IDBG-73381 (CSNK1D)

Protein Structure

UniProt Annotation

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. In balance with PP1, determines the circadian period length through the regulation of the speed and rhythmicity of PER1 and PER2 phospohorylation. Controls PER1 and PER2 nuclear transport and degradation. 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. {ECO:0000269PubMed:10606744, ECO:0000269PubMed:12270943, ECO:0000269PubMed:14761950, ECO:0000269PubMed:16027726, ECO:0000269PubMed:17562708, ECO:0000269PubMed:17962809, ECO:0000269PubMed:19043076, ECO:0000269PubMed:19339517, ECO:0000269PubMed:20041275, ECO:0000269PubMed:20048001, ECO:0000269PubMed:20407760, ECO:0000269PubMed:20637175, ECO:0000269PubMed:20696890, ECO:0000269PubMed:20699359, ECO:0000269PubMed:21084295, ECO:0000269PubMed:21422228, ECO:0000269PubMed:23636092}.

Subcellular Localization

Cytoplasm. Nucleus. Cytoplasm, cytoskeleton, microtubule organizing center, centrosome. Cytoplasm, perinuclear region. Cell membrane. Cytoplasm, cytoskeleton, spindle. 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.

Disease Associations

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. {ECO:0000269PubMed:15800623, ECO:0000269PubMed:23636092}. Note=The disease is caused by mutations affecting the gene represented in this entry.

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. {ECO:0000269PubMed:15070676, ECO:0000269PubMed:16027726}.

Comments

Interactions

Number of Interactions

This gene and/or its encoded proteins are associated with 53 experimentally validated interaction(s) in this database.
They are also associated with 5 interaction(s) predicted by orthology.

Experimentally validated
Total	53 [view]
Protein-Protein	50 [view]
Protein-DNA	0
Protein-RNA	0
DNA-DNA	3 [view]
RNA-RNA	0
DNA-RNA	0

Predicted by orthology
Total	5 [view]

Gene Ontology

Molecular Function

Accession	GO Term
GO:0004672	protein kinase activity
GO:0004713	protein tyrosine kinase activity
GO:0005515	protein binding
GO:0005524	ATP binding
GO:0016772	transferase activity, transferring phosphorus-containing groups
GO:0050321	tau-protein kinase activity

Biological Process

GO:0000086	G2/M transition of mitotic cell cycle
GO:0000278	mitotic cell cycle
GO:0001934	positive regulation of protein phosphorylation
GO:0006281	DNA repair
GO:0006468	protein phosphorylation
GO:0007165	signal transduction
GO:0016055	Wnt signaling pathway
GO:0032436	positive regulation of proteasomal ubiquitin-dependent protein catabolic process
GO:0032922	circadian regulation of gene expression
GO:0042752	regulation of circadian rhythm
GO:0051225	spindle assembly
GO:0090263	positive regulation of canonical Wnt signaling pathway

Cellular Component

GO:0005634	nucleus
GO:0005794	Golgi apparatus
GO:0005813	centrosome
GO:0005819	spindle
GO:0005829	cytosol
GO:0005876	spindle microtubule
GO:0005886	plasma membrane
GO:0048471	perinuclear region of cytoplasm

Protein Structure and Domains

PDB ID

InterPro

IPR000719 Protein kinase domain
IPR001245 Serine-threonine/tyrosine-protein kinase catalytic domain
IPR002290 Serine/threonine/dual specificity protein kinase, catalytic domain
IPR011009 Protein kinase-like domain
IPR020635 Tyrosine-protein kinase, catalytic domain

PFAM

PF00069
PF07714

PRINTS

PR00109

PIRSF

SMART

SM00220
SM00219

TIGRFAMs

Post-translational Modifications

Modification

Cross-References

SwissProt