ID:KC1D_HUMAN DESCRIPTION: RecName: Full=Casein kinase I isoform delta; Short=CKI-delta; Short=CKId; EC=2.7.11.1; AltName: Full=Tau-protein kinase CSNK1D; EC=2.7.11.26; 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. CATALYTIC ACTIVITY: ATP + a protein = ADP + a phosphoprotein. CATALYTIC ACTIVITY: ATP + [tau protein] = ADP + [tau protein] phosphate. 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-sulphonamide (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). SUBUNIT: 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. INTERACTION: Q00987:MDM2; NbExp=6; IntAct=EBI-751621, EBI-389668; SUBCELLULAR LOCATION: Cytoplasm. Nucleus. Cytoplasm, cytoskeleton, 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. 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. DEVELOPMENTAL STAGE: Highly present in extravillous trophoblast cells, which are present at the placenta implantation site and invade the decidua and decidual vessels. PTM: Autophosphorylated on serine and threonine residues; this autophosphorylation represses activity. Reactivated by phosphatase-mediated dephosphorylation. DISEASE: Defects in CSNK1D are a cause of familial advanced sleep- phase syndrome (FASPS) [MIM:604348]. FASPS is characterized by very early sleep onset and offset. Individuals are 'morning larks' with a 4 hours advance of the sleep, temperature and melatonin rhythms. MISCELLANEOUS: May be involved in Alzheimer disease by phosphorylating MAPT/TAU (PubMed:17562708). SIMILARITY: Belongs to the protein kinase superfamily. CK1 Ser/Thr protein kinase family. Casein kinase I subfamily. SIMILARITY: Contains 1 protein kinase domain. CAUTION: Was shown to phosphorylate and activate DCK in vitro but probably not in vivo (PubMed:20637175).
The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.
ModBase Predicted Comparative 3D Structure on P48730
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Orthologous Genes in Other Species
Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
AB209463 - Homo sapiens mRNA for casein kinase 1, delta isoform 1 variant protein. AB091044 - Homo sapiens CKId mRNA for casein kinase I delta, complete cds. U29171 - Human casein kinase I delta mRNA, complete cds. BC003558 - Homo sapiens casein kinase 1, delta, mRNA (cDNA clone MGC:1768 IMAGE:3546633), complete cds. BC015775 - Homo sapiens casein kinase 1, delta, mRNA (cDNA clone MGC:23540 IMAGE:4849869), complete cds. BC065489 - Homo sapiens cDNA clone IMAGE:6266394, **** WARNING: chimeric clone ****. BC080619 - Homo sapiens casein kinase 1, delta, mRNA (cDNA clone IMAGE:6254029), **** WARNING: chimeric clone ****. AK295638 - Homo sapiens cDNA FLJ55976 complete cds, highly similar to Casein kinase I isoform delta (EC 2.7.11.1). AK303365 - Homo sapiens cDNA FLJ56279 complete cds, highly similar to Casein kinase I isoform delta (EC 2.7.11.1). KJ896662 - Synthetic construct Homo sapiens clone ccsbBroadEn_06056 CSNK1D gene, encodes complete protein. KJ905183 - Synthetic construct Homo sapiens clone ccsbBroadEn_14600 CSNK1D gene, encodes complete protein. AB527595 - Synthetic construct DNA, clone: pF1KB6629, Homo sapiens CSNK1D gene for casein kinase 1, delta, without stop codon, in Flexi system. AK291758 - Homo sapiens cDNA FLJ76667 complete cds, highly similar to Homo sapiens casein kinase 1, delta (CSNK1D), transcript variant 2, mRNA. KJ890984 - Synthetic construct Homo sapiens clone ccsbBroadEn_00378 CSNK1D gene, encodes complete protein. KR710527 - Synthetic construct Homo sapiens clone CCSBHm_00013805 CSNK1D (CSNK1D) mRNA, encodes complete protein. EU832350 - Synthetic construct Homo sapiens clone HAIB:100067379; DKFZo008H0427 casein kinase 1, delta protein (CSNK1D) gene, encodes complete protein. EU832435 - Synthetic construct Homo sapiens clone HAIB:100067464; DKFZo004H0428 casein kinase 1, delta protein (CSNK1D) gene, encodes complete protein. AK296969 - Homo sapiens cDNA FLJ50568 complete cds, highly similar to Casein kinase I isoform delta (EC 2.7.11.1). CU677441 - Synthetic construct Homo sapiens gateway clone IMAGE:100023244 5' read CSNK1D mRNA. CU678502 - Synthetic construct Homo sapiens gateway clone IMAGE:100019292 5' read CSNK1D mRNA. AK096950 - Homo sapiens cDNA FLJ39631 fis, clone SMINT2002210. BC047000 - Homo sapiens, clone IMAGE:3869896, mRNA. JD225498 - Sequence 206522 from Patent EP1572962. JD405797 - Sequence 386821 from Patent EP1572962. JD227665 - Sequence 208689 from Patent EP1572962. JD170792 - Sequence 151816 from Patent EP1572962. JD530540 - Sequence 511564 from Patent EP1572962. JD501135 - Sequence 482159 from Patent EP1572962. JD159391 - Sequence 140415 from Patent EP1572962. JD364832 - Sequence 345856 from Patent EP1572962. JD119536 - Sequence 100560 from Patent EP1572962. JD149907 - Sequence 130931 from Patent EP1572962. JD123874 - Sequence 104898 from Patent EP1572962. JD460346 - Sequence 441370 from Patent EP1572962. JD165119 - Sequence 146143 from Patent EP1572962. JD058283 - Sequence 39307 from Patent EP1572962. JD300225 - Sequence 281249 from Patent EP1572962. JD494961 - Sequence 475985 from Patent EP1572962. JD092740 - Sequence 73764 from Patent EP1572962. JD123833 - Sequence 104857 from Patent EP1572962. JD163602 - Sequence 144626 from Patent EP1572962. JD077664 - Sequence 58688 from Patent EP1572962. JD458722 - Sequence 439746 from Patent EP1572962. JD341893 - Sequence 322917 from Patent EP1572962. JD107910 - Sequence 88934 from Patent EP1572962. JD152054 - Sequence 133078 from Patent EP1572962. JD184574 - Sequence 165598 from Patent EP1572962. JD265980 - Sequence 247004 from Patent EP1572962. JD260257 - Sequence 241281 from Patent EP1572962. AK128863 - Homo sapiens cDNA FLJ46820 fis, clone TSTOM2001571, highly similar to Casein kinase I, delta isoform (EC 2.7.1.-). JD232114 - Sequence 213138 from Patent EP1572962. JD480836 - Sequence 461860 from Patent EP1572962. JD476578 - Sequence 457602 from Patent EP1572962. JD092113 - Sequence 73137 from Patent EP1572962. JD417257 - Sequence 398281 from Patent EP1572962. AK311248 - Homo sapiens cDNA, FLJ18290. JD390159 - Sequence 371183 from Patent EP1572962. JD080491 - Sequence 61515 from Patent EP1572962. JD220527 - Sequence 201551 from Patent EP1572962. AK308852 - Homo sapiens cDNA, FLJ98893. DQ590396 - Homo sapiens piRNA piR-57508, complete sequence. U31285 - Human casein kinase I delta RNA, partial cds. JD406304 - Sequence 387328 from Patent EP1572962. JD068423 - Sequence 49447 from Patent EP1572962. JD336731 - Sequence 317755 from Patent EP1572962. JD336807 - Sequence 317831 from Patent EP1572962. JD211421 - Sequence 192445 from Patent EP1572962.
Biochemical and Signaling Pathways
BioCarta from NCI Cancer Genome Anatomy Project h_ck1Pathway - Regulation of ck1/cdk5 by type 1 glutamate receptors
Reactome (by CSHL, EBI, and GO)
Protein P48730 (Reactome details) participates in the following event(s):
R-HSA-380272 Plk1-mediated phosphorylation of Nlp R-HSA-380283 Recruitment of additional gamma tubulin/ gamma TuRC to the centrosome R-HSA-380294 Loss of C-Nap-1 from centrosomes R-HSA-380311 Recruitment of Plk1 to centrosomes R-HSA-380455 Recruitment of CDK11p58 to the centrosomes R-HSA-380303 Dissociation of Phospho-Nlp from the centrosome R-HSA-5626220 C2CD3 binds the mother centriole R-HSA-5694441 CSNK1D phosphorylates SEC23 R-HSA-380508 Translocation of NuMA to the centrosomes R-HSA-2574845 AJUBA binds centrosome-associated AURKA R-HSA-8853405 TPX2 binds AURKA at centrosomes R-HSA-3000319 BORA binds PLK1 and AURKA R-HSA-2574840 AJUBA facilitates AURKA autophosphorylation R-HSA-3000310 AURKA phosphorylates PLK1 R-HSA-5626223 C2CD3 and OFD1 recruit 5 distal appendage proteins to the centriole R-HSA-5626681 Recruitment of transition zone proteins R-HSA-5626227 CP110 and CEP97 dissociate from the centriole R-HSA-400382 CSNK1E,CSNK1D phosphorylate CRY and PER proteins R-HSA-400256 CRY:PER heterodimer binds the BMAL1:CLOCK/NPAS2 heterodimer R-HSA-380316 Association of NuMA with microtubules R-HSA-8853419 TPX2 promotes AURKA autophosphorylation R-HSA-5626228 The distal appendage proteins recruit TTBK2 R-HSA-5638009 CEP164 recruits RAB3IP-carrying Golgi-derived vesicles to the basal body R-HSA-5626699 MARK4 binds ODF2 in the centriole R-HSA-5617816 RAB3IP stimulates nucleotide exchange on RAB8A R-HSA-6791226 Major pathway of rRNA processing in the nucleolus and cytosol R-HSA-380259 Loss of Nlp from mitotic centrosomes R-HSA-380270 Recruitment of mitotic centrosome proteins and complexes R-HSA-380284 Loss of proteins required for interphase microtubule organization from the centrosome R-HSA-5620912 Anchoring of the basal body to the plasma membrane R-HSA-400253 Circadian Clock R-HSA-8868773 rRNA processing in the nucleus and cytosol R-HSA-204005 COPII-mediated vesicle transport R-HSA-380320 Recruitment of NuMA to mitotic centrosomes R-HSA-2565942 Regulation of PLK1 Activity at G2/M Transition R-HSA-8854518 AURKA Activation by TPX2 R-HSA-380287 Centrosome maturation R-HSA-5617833 Cilium Assembly R-HSA-72312 rRNA processing R-HSA-199977 ER to Golgi Anterograde Transport R-HSA-68877 Mitotic Prometaphase R-HSA-69275 G2/M Transition R-HSA-1852241 Organelle biogenesis and maintenance R-HSA-8953854 Metabolism of RNA R-HSA-199991 Membrane Trafficking R-HSA-948021 Transport to the Golgi and subsequent modification R-HSA-68886 M Phase R-HSA-453274 Mitotic G2-G2/M phases R-HSA-5653656 Vesicle-mediated transport R-HSA-446203 Asparagine N-linked glycosylation R-HSA-69278 Cell Cycle (Mitotic) R-HSA-597592 Post-translational protein modification R-HSA-1640170 Cell Cycle R-HSA-392499 Metabolism of proteins
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Sequence and Links to Tools and Databases 
Common Gene Haplotype Alleles 
