Gene Symbol: Csnk1e
Description: casein kinase 1, epsilon
Alias: AI426939, AI551861, AW457082, CK1epsilon, CKIe, KC1epsilon, tau, casein kinase I isoform epsilon, casein kinase I, CKI-epsilon, KC1 epsilon
Species: mouse
Products:     Csnk1e

Top Publications

  1. Bryja V, Schulte G, Arenas E. Wnt-3a utilizes a novel low dose and rapid pathway that does not require casein kinase 1-mediated phosphorylation of Dvl to activate beta-catenin. Cell Signal. 2007;19:610-6 pubmed
    ..Thus, our results show that Wnt-3a rapidly induce a partial activation of beta-catenin in the absence of PS-Dvl at low doses, while at high doses induce a full activation of beta-catenin in a PS-Dvl-dependent manner. ..
  2. Lowrey P, Shimomura K, Antoch M, Yamazaki S, Zemenides P, Ralph M, et al. Positional syntenic cloning and functional characterization of the mammalian circadian mutation tau. Science. 2000;288:483-92 pubmed
    ..The tau locus is encoded by casein kinase I epsilon (CKIepsilon), a homolog of the Drosophila circadian gene double-time...
  3. Lee H, Chen R, Kim H, Etchegaray J, Weaver D, Lee C. The period of the circadian oscillator is primarily determined by the balance between casein kinase 1 and protein phosphatase 1. Proc Natl Acad Sci U S A. 2011;108:16451-6 pubmed publisher
    ..Thus, our findings provide clear insights into the molecular basis of how the period and phase of our daily rhythms are determined. ..
  4. Meng Q, Maywood E, Bechtold D, Lu W, Li J, Gibbs J, et al. Entrainment of disrupted circadian behavior through inhibition of casein kinase 1 (CK1) enzymes. Proc Natl Acad Sci U S A. 2010;107:15240-5 pubmed publisher
    ..We selectively targeted WT CK1epsilon and CK1delta using pharmacological inhibitors (PF-4800567 and PF-670462, respectively) alongside genetic ..
  5. Maywood E, Chesham J, O Brien J, Hastings M. A diversity of paracrine signals sustains molecular circadian cycling in suprachiasmatic nucleus circuits. Proc Natl Acad Sci U S A. 2011;108:14306-11 pubmed publisher
    ..Thus, a hierarchy of paracrine neuropeptidergic signals determines cell- and circuit-level circadian pacemaking in the SCN. ..
  6. Cong F, Schweizer L, Varmus H. Casein kinase Iepsilon modulates the signaling specificities of dishevelled. Mol Cell Biol. 2004;24:2000-11 pubmed
    ..We suggest that CKIepsilon functions as a molecular switch to direct Dvl from the JNK pathway to the beta-catenin pathway, possibly by altering the conformation of the C terminus of Dvl. ..
  7. Lee C, Weaver D, Reppert S. Direct association between mouse PERIOD and CKIepsilon is critical for a functioning circadian clock. Mol Cell Biol. 2004;24:584-94 pubmed
    ..We thus propose that the CKIepsilon-binding domain is critical not only for mPER phosphorylation but also for a functioning circadian clock. ..
  8. Isojima Y, Nakajima M, Ukai H, Fujishima H, Yamada R, Masumoto K, et al. CKIepsilon/delta-dependent phosphorylation is a temperature-insensitive, period-determining process in the mammalian circadian clock. Proc Natl Acad Sci U S A. 2009;106:15744-9 pubmed publisher
    ..Thus, CKIepsilon/delta-dependent phosphorylation is likely a temperature-insensitive period-determining process in the mammalian circadian clock. ..
  9. Lee H, Chen R, Lee Y, Yoo S, Lee C. Essential roles of CKIdelta and CKIepsilon in the mammalian circadian clock. Proc Natl Acad Sci U S A. 2009;106:21359-64 pubmed publisher
    ..Our results show that an essential role of CKIdelta/epsilon is conserved between Drosophila and mammals, but CKIdelta/epsilon and DBT may have divergent non-catalytic functions in the clockwork as well. ..

More Information


  1. Vielhaber E, Eide E, Rivers A, Gao Z, Virshup D. Nuclear entry of the circadian regulator mPER1 is controlled by mammalian casein kinase I epsilon. Mol Cell Biol. 2000;20:4888-99 pubmed
    ..The Drosophila double-time gene product, a casein kinase I epsilon (CKIepsilon) homolog, has been reported to interact with dPER and regulate circadian cycle length...
  2. Meng Q, Logunova L, Maywood E, Gallego M, Lebiecki J, Brown T, et al. Setting clock speed in mammals: the CK1 epsilon tau mutation in mice accelerates circadian pacemakers by selectively destabilizing PERIOD proteins. Neuron. 2008;58:78-88 pubmed publisher
    ..Circadian period lengthened in CK1epsilon-/-, whereas CK1epsilon(tau/tau) shortened circadian period of behavior in vivo and suprachiasmatic nucleus ..
  3. Bryja V, Schulte G, Rawal N, Grahn A, Arenas E. Wnt-5a induces Dishevelled phosphorylation and dopaminergic differentiation via a CK1-dependent mechanism. J Cell Sci. 2007;120:586-95 pubmed
    ..Using in vitro gain-of-function and loss-of-function approaches, we reveal that casein kinase 1 (CK1) delta and CK1epsilon are crucial for Dvl phosphorylation by non-canonical Wnts...
  4. Etchegaray J, Machida K, Noton E, Constance C, Dallmann R, Di Napoli M, et al. Casein kinase 1 delta regulates the pace of the mammalian circadian clock. Mol Cell Biol. 2009;29:3853-66 pubmed publisher
    Both casein kinase 1 delta (CK1delta) and epsilon (CK1epsilon) phosphorylate core clock proteins of the mammalian circadian oscillator...
  5. Eide E, Woolf M, Kang H, Woolf P, Hurst W, Camacho F, et al. Control of mammalian circadian rhythm by CKIepsilon-regulated proteasome-mediated PER2 degradation. Mol Cell Biol. 2005;25:2795-807 pubmed
    ..Cell culture-based biochemical assays combined with measurement of cell-based rhythm complement genetic studies to elucidate basic mechanisms controlling the mammalian clock. ..
  6. Duong H, Robles M, Knutti D, Weitz C. A molecular mechanism for circadian clock negative feedback. Science. 2011;332:1436-9 pubmed publisher
    ..These findings provide a function for the PER complex and a molecular mechanism for circadian clock negative feedback. ..
  7. Sakanaka C. Phosphorylation and regulation of beta-catenin by casein kinase I epsilon. J Biochem. 2002;132:697-703 pubmed
    ..Mutations at those two sites, as well as in Ser-45, stabilize beta-catenin. Recently, casein kinase I epsilon (CKI epsilon) has been shown to be a positive regulator of the Wnt pathway...
  8. Young E, Bryant C, Lee S, Peng X, Cook B, Nair H, et al. Systems genetic and pharmacological analysis identifies candidate genes underlying mechanosensation in the von Frey test. Genes Brain Behav. 2016;15:604-15 pubmed publisher
    ..within the loci: von Frey thresholds were strongly correlated with baseline expression of Cacna2d1, Ift27 and Csnk1e in multiple brain regions of BXD strains...
  9. Spoelstra K, Wikelski M, Daan S, Loudon A, Hau M. Natural selection against a circadian clock gene mutation in mice. Proc Natl Acad Sci U S A. 2016;113:686-91 pubmed publisher
    ..We tested this hypothesis in mice bearing a short-period mutation in the enzyme casein kinase 1ε (tau mutation), which accelerates free-running circadian cycles...
  10. Wallach T, Schellenberg K, Maier B, Kalathur R, Porras P, Wanker E, et al. Dynamic circadian protein-protein interaction networks predict temporal organization of cellular functions. PLoS Genet. 2013;9:e1003398 pubmed publisher
    ..Moreover, we predict that circadian PPIs dynamically connect many important cellular processes (signal transduction, cell cycle, etc.) contributing to temporal organization of cellular physiology in an unprecedented manner. ..
  11. Duong H, Weitz C. Temporal orchestration of repressive chromatin modifiers by circadian clock Period complexes. Nat Struct Mol Biol. 2014;21:126-32 pubmed publisher
    ..Circadian clock negative feedback by the PER complex thus involves dynamic, ordered recruitment of repressive chromatin modifiers to DNA-bound Clock-Bmal1. ..
  12. Sharma S, Findlay G, Bandukwala H, Oberdoerffer S, Baust B, Li Z, et al. Dephosphorylation of the nuclear factor of activated T cells (NFAT) transcription factor is regulated by an RNA-protein scaffold complex. Proc Natl Acad Sci U S A. 2011;108:11381-6 pubmed publisher
  13. Goldberg L, Kirkpatrick S, Yazdani N, Luttik K, Lacki O, Babbs R, et al. Casein kinase 1-epsilon deletion increases mu opioid receptor-dependent behaviors and binge eating1. Genes Brain Behav. 2017;16:725-738 pubmed publisher
    Genetic and pharmacological studies indicate that casein kinase 1 epsilon (Csnk1e) contributes to psychostimulant, opioid, and ethanol motivated behaviors...
  14. Novellasdemunt L, Foglizzo V, Cuadrado L, Antas P, Kucharska A, Encheva V, et al. USP7 Is a Tumor-Specific WNT Activator for APC-Mutated Colorectal Cancer by Mediating ?-Catenin Deubiquitination. Cell Rep. 2017;21:612-627 pubmed publisher
    ..Finally, the Wnt-activating role of USP7 is specific to APC mutations; thus, it can be used as a tumor-specific therapeutic target for most CRCs. ..
  15. Liu F, Virshup D, Nairn A, Greengard P. Mechanism of regulation of casein kinase I activity by group I metabotropic glutamate receptors. J Biol Chem. 2002;277:45393-9 pubmed
    ..Metabolic labeling studies and phosphopeptide mapping revealed that a set of C-terminal sites in HA-CK1epsilon were transiently dephosphorylated in N2a cells upon treatment with DHPG, and this was blocked by cyclosporin A...
  16. Utz A, Hirner H, Blatz A, Hillenbrand A, Schmidt B, Deppert W, et al. Analysis of cell type-specific expression of CK1 epsilon in various tissues of young adult BALB/c Mice and in mammary tumors of SV40 T-Ag-transgenic mice. J Histochem Cytochem. 2010;58:1-15 pubmed publisher
    Casein kinase 1 epsilon (CK1epsilon) is involved in various cellular processes, including cell growth, differentiation, and apoptosis, vesicle transport, and control of the circadian rhythm...
  17. Cheng M, Bullock C, Li C, Lee A, Bermak J, Belluzzi J, et al. Prokineticin 2 transmits the behavioural circadian rhythm of the suprachiasmatic nucleus. Nature. 2002;417:405-10 pubmed
    ..The high expression of PKR2 mRNA within the SCN and the positive feedback of PK2 on its own transcription through activation of PKR2 suggest that PK2 may also function locally within the SCN to synchronize output. ..
  18. St John P, Hirota T, Kay S, Doyle F. Spatiotemporal separation of PER and CRY posttranslational regulation in the mammalian circadian clock. Proc Natl Acad Sci U S A. 2014;111:2040-5 pubmed publisher
    ..As a result, this study provides further insight into the molecular clock machinery responsible for maintaining robust circadian rhythms. ..
  19. Cajanek L, Ganji R, Henriques Oliveira C, Theofilopoulos S, Konik P, Bryja V, et al. Tiam1 regulates the Wnt/Dvl/Rac1 signaling pathway and the differentiation of midbrain dopaminergic neurons. Mol Cell Biol. 2013;33:59-70 pubmed publisher
    ..In summary, our data identify Tiam1 as a novel regulator of DA neuron development and as a Dvl-associated and Rac1-specific GEF acting in the Wnt/Dvl/Rac1 pathway. ..
  20. Kusuda J, Hidari N, Hirai M, Hashimoto K. Sequence analysis of the cDNA for the human casein kinase I delta (CSNK1D) gene and its chromosomal localization. Genomics. 1996;32:140-3 pubmed
    A cDNA clone coding for human casein kinase I (CK1) has been isolated and sequenced. The insert of 1911 bp contained an open reading frame of 415 amino acids...
  21. Hirota T, Lee J, Lewis W, Zhang E, Breton G, Liu X, et al. High-throughput chemical screen identifies a novel potent modulator of cellular circadian rhythms and reveals CKI? as a clock regulatory kinase. PLoS Biol. 2010;8:e1000559 pubmed publisher
    ..Longdaysin provides novel possibilities in manipulating clock function due to its ability to simultaneously inhibit several key components of this conserved network across species. ..
  22. Schwarz Romond T, Metcalfe C, Bienz M. Dynamic recruitment of axin by Dishevelled protein assemblies. J Cell Sci. 2007;120:2402-12 pubmed
    ..We discuss how the recruitment of casein kinase Iepsilon by Dvl2 assemblies might impact on the recruitment of axin to the plasma membrane during Wnt signalling. ..
  23. Palmer A, Verbitsky M, Suresh R, Kamens H, Reed C, Li N, et al. Gene expression differences in mice divergently selected for methamphetamine sensitivity. Mamm Genome. 2005;16:291-305 pubmed
    ..The identified genes provide excellent candidates for future hypothesis-driven studies, translational genetic studies, and pharmacological interventions. ..
  24. Ha N, Tonozuka T, Stamos J, Choi H, Weis W. Mechanism of phosphorylation-dependent binding of APC to beta-catenin and its role in beta-catenin degradation. Mol Cell. 2004;15:511-21 pubmed
    ..The role of APC in this process is poorly understood. CK1epsilon and GSK-3beta phosphorylate APC, which increases its affinity for beta-catenin...
  25. Mallampati S, Sun B, Lu Y, Ma H, Gong Y, Wang D, et al. Integrated genetic approaches identify the molecular mechanisms of Sox4 in early B-cell development: intricate roles for RAG1/2 and CK1?. Blood. 2014;123:4064-76 pubmed publisher
  26. Brancaccio M, Patton A, Chesham J, Maywood E, Hastings M. Astrocytes Control Circadian Timekeeping in the Suprachiasmatic Nucleus via Glutamatergic Signaling. Neuron. 2017;93:1420-1435.e5 pubmed publisher
    ..Thus, SCN circuit-level timekeeping arises from interdependent and mutually supportive astrocytic-neuronal signaling. ..
  27. Schneider K, Kocher T, Andersin T, Kurzchalia T, Schibler U, Gatfield D. CAVIN-3 regulates circadian period length and PER:CRY protein abundance and interactions. EMBO Rep. 2012;13:1138-44 pubmed publisher
    ..This suggests the involvement of yet uncharacterized protein kinases. Finally, CAVIN-3 activity in circadian gene expression was independent of caveolae. ..
  28. Zhou L, Bryant C, Loudon A, Palmer A, Vitaterna M, Turek F. The circadian clock gene Csnk1e regulates rapid eye movement sleep amount, and nonrapid eye movement sleep architecture in mice. Sleep. 2014;37:785-93, 793A-793C pubmed publisher
    ..approaches to identify and test a positional candidate sleep gene - the circadian gene casein kinase 1 epsilon (Csnk1e), which is located in a QTL we identified for rapid eye movement (REM) sleep on chromosome 15...
  29. Zhou Y, He C, Yan D, Liu F, Liu H, Chen J, et al. The kinase CK1É› controls the antiviral immune response by phosphorylating the signaling adaptor TRAF3. Nat Immunol. 2016;17:397-405 pubmed publisher
    ..Our findings establish CK1É› as a regulator of antiviral innate immune responses and indicate a novel mechanism of immunoregulation that involves CK1É›-mediated phosphorylation of TRAF3. ..
  30. Kusuda J, Hirai M, Tanuma R, Hashimoto K. cDNA cloning and chromosome mapping of the mouse casein kinase I epsilon gene (Csnk1e). Cytogenet Cell Genet. 1999;87:99-101 pubmed
  31. Greer Y, Rubin J. Casein kinase 1 delta functions at the centrosome to mediate Wnt-3a-dependent neurite outgrowth. J Cell Biol. 2011;192:993-1004 pubmed publisher
    ..These results provide strong evidence that the centrosomal localization of CK1? is required for Wnt-3a-dependent neuritogenesis. ..
  32. Maywood E, Chesham J, Meng Q, Nolan P, Loudon A, Hastings M. Tuning the period of the mammalian circadian clock: additive and independent effects of CK1?Tau and Fbxl3Afh mutations on mouse circadian behavior and molecular pacemaking. J Neurosci. 2011;31:1539-44 pubmed publisher
    ..two mutations in male mice: Fbxl3(Afh), which lengthens period by stabilizing CRY, and Csnk1?(tm1Asil) (CK1?(Tau)), which destabilizes PER, thereby accelerating the clock...
  33. Mohawk J, Baer M, Menaker M. The methamphetamine-sensitive circadian oscillator does not employ canonical clock genes. Proc Natl Acad Sci U S A. 2009;106:3519-24 pubmed publisher
    ..The properties of MASCO may provide insight into the evolution of circadian mechanisms. Importantly, MASCO may play a role in addiction to psychostimulants. ..
  34. Swiatek W, Tsai I, Klimowski L, Pepler A, Barnette J, Yost H, et al. Regulation of casein kinase I epsilon activity by Wnt signaling. J Biol Chem. 2004;279:13011-7 pubmed
    ..Activation of the Wnt pathway may therefore stimulate a cellular phosphatase to dephosphorylate and activate CKIepsilon ..
  35. Umar S, Wang Y, Morris A, Sellin J. Dual alterations in casein kinase I-epsilon and GSK-3beta modulate beta-catenin stability in hyperproliferating colonic epithelia. Am J Physiol Gastrointest Liver Physiol. 2007;292:G599-607 pubmed
    b>Casein kinase I (CKI)-epsilon and GSK-3beta phosphorylate beta-catenin at Ser(45) (beta-cat(45)) and Thr(41)/Ser(37,33) (beta-cat(33,37,41)) residues, thereby facilitating its ubiquitination and proteasomal degradation...
  36. Flajolet M, He G, Heiman M, Lin A, Nairn A, Greengard P. Regulation of Alzheimer's disease amyloid-beta formation by casein kinase I. Proc Natl Acad Sci U S A. 2007;104:4159-64 pubmed
    ..Overexpression of constitutively active CK1epsilon, one of the CK1 isoforms expressed in brain, leads to an increase in Abeta peptide production...
  37. Etchegaray J, Yu E, Indic P, Dallmann R, Weaver D. Casein kinase 1 delta (CK1delta) regulates period length of the mouse suprachiasmatic circadian clock in vitro. PLoS ONE. 2010;5:e10303 pubmed publisher
    ..a more prominent role in the regulation of circadian cycle length than its homologue casein kinase 1 epsilon (CK1epsilon) in peripheral tissues such as liver and embryonic fibroblasts...
  38. Kato K, Bhattaram P, Penzo Méndez A, Gadi A, Lefebvre V. SOXC Transcription Factors Induce Cartilage Growth Plate Formation in Mouse Embryos by Promoting Noncanonical WNT Signaling. J Bone Miner Res. 2015;30:1560-71 pubmed publisher
    ..ligand required for growth plate formation, and in chondrocytes and perichondrocytes for expression of Fzd3 and Csnk1e, which encode a WNT receptor and casein kinase-1 subunit mediating planar cell polarity, respectively...
  39. Shen T, Cseresnyes Z, Liu Y, Randall W, Schneider M. Regulation of the nuclear export of the transcription factor NFATc1 by protein kinases after slow fibre type electrical stimulation of adult mouse skeletal muscle fibres. J Physiol. 2007;579:535-51 pubmed
  40. Wolff S, Stöter M, Giamas G, Piesche M, Henne Bruns D, Banting G, et al. Casein kinase 1 delta (CK1delta) interacts with the SNARE associated protein snapin. FEBS Lett. 2006;580:6477-84 pubmed
    ..The identification of snapin as a new substrate of CK1delta points towards a possible function for CK1delta in modulating snapin specific functions. ..
  41. Morgenstern Y, Das Adhikari U, Ayyash M, Elyada E, Tóth B, Moor A, et al. Casein kinase 1-epsilon or 1-delta required for Wnt-mediated intestinal stem cell maintenance. EMBO J. 2017;36:3046-3061 pubmed publisher
    ..Our study underscores a unique regulation mode of the Wnt pathway in ISCs, possibly providing new means of stem cell enrichment for regenerative medicine. ..
  42. Maywood E, Chesham J, Smyllie N, Hastings M. The Tau mutation of casein kinase 1? sets the period of the mammalian pacemaker via regulation of Period1 or Period2 clock proteins. J Biol Rhythms. 2014;29:110-8 pubmed publisher
    ..individual mutations in either hCK1 or hPER2 lead to advanced sleep phase disorders, whereas in rodents, the Tau mutation of CK1 epsilon (CK1? (Tau)) accelerates rest-activity cycles and shortens the period of the SCN molecular ..
  43. Scoma H, Humby M, Yadav G, Zhang Q, Fogerty J, Besharse J. The de-ubiquitinylating enzyme, USP2, is associated with the circadian clockwork and regulates its sensitivity to light. PLoS ONE. 2011;6:e25382 pubmed publisher
    ..Rhythmic expression of USP2 in the SCN and other tissues offers a new level of control of the clock machinery through de-ubiqutinylation and suggests a role for USP2 during circadian adaptation to environmental day length changes. ..
  44. Chergui K, Svenningsson P, Greengard P. Physiological role for casein kinase 1 in glutamatergic synaptic transmission. J Neurosci. 2005;25:6601-9 pubmed
    ..These results provide the first evidence for a role of CK1 in the regulation of synaptic transmission in the brain. ..
  45. Sugiyama Y, Hatano N, Sueyoshi N, Suetake I, Tajima S, Kinoshita E, et al. The DNA-binding activity of mouse DNA methyltransferase 1 is regulated by phosphorylation with casein kinase 1delta/epsilon. Biochem J. 2010;427:489-97 pubmed publisher
    ..These results suggest that CK1delta/epsilon binds to and phosphorylates the N-terminal domain of Dnmt1 and regulates Dnmt1 function by reducing the DNA-binding activity. ..
  46. Bryant C, PARKER C, Zhou L, Olker C, Chandrasekaran R, Wager T, et al. Csnk1e is a genetic regulator of sensitivity to psychostimulants and opioids. Neuropsychopharmacology. 2012;37:1026-35 pubmed publisher
    b>Csnk1e, the gene encoding casein kinase 1-epsilon, has been implicated in sensitivity to amphetamines...
  47. Lee K, Johmura Y, Yu L, Park J, Gao Y, Bang J, et al. Identification of a novel Wnt5a-CK1?-Dvl2-Plk1-mediated primary cilia disassembly pathway. EMBO J. 2012;31:3104-17 pubmed publisher
    ..This study may provide new insights into the mechanism underlying ciliary disassembly processes and various cilia-related disorders. ..