CSNK1A1 (casein kinase 1, alpha 1)

2008-05-01   Max Doerfel , Otmar Huber 

Department of Laboratory Medicine, Pathobiochemistry, Charite - Universitatsmedizin Berlin, Campus Benjamin Franklin, Hindenburgdamm 30, 12203 Berlin, Germany




Atlas Image
Diagram of hCK1 alpha gene. Exons for both isoforms are presented as red boxes, with exon mumbers at the bottom.


According to Entrez-Gene, CNK1 alpha1 gene maps to NC_000005.8.


In mammals, 7 distinct genes encoding CK1 isoforms (CK1 alpha, CK1 beta, CK1 gamma1, CK1 gamma2, CK1 gamma3, CK1 delta and CK1 epsilon) are expressed which differ mainly in length and primary structure of the C-terminal non-catalytic domain. Furthermore, CK1 alpha splice variants have been detected in many different organisms including vertebrates and mammals. Alternative splicing leads to the insertion of a long (L, 28 aa) or a short (S, 12 aa) insert into the catalytic C-terminal domain of CK1 alpha and generates different splicing products (CK1 alpha, CK1 alphaL, CK1 alphaS, CK2 alphaLS, alpha3) that differ in kinase activity, function and subcellular localization.
In humans at least two isoforms of CK1 alpha have been identified encoding a 3149 bp (isoform1/NM_001025105) or 3061 bp (isoform2/NM_001892) mRNA, respectively.



The hCK1 alpha isoforms are composed of 365 or 337 amino acids and have a calculated molecular weight of 41,9 or 38,9 kDa, respectively. Both isoforms contain a putative near-consensus SV40 T-antigen nuclear localization sequence.


CK1 alpha is a second messenger-independent, monomeric, serine/threonine specific protein kinase that recognizes a canonical consensus sequence pS/pT-X1-2-S/T or (D/E)-X1-2-S/T. Additionally, a noncanonical sequence containing a SLS motif followed by a cluster of acidic residues C-terminal of the phosphoacceptor site is recognized by CK1.


The protein kinase CK1 alpha is ubiquitously expressed in all tissues and detected in all cellular compartments.


Mammalian CK1 isoforms and their splice variants are involved in diverse cellular processes including membrane trafficking, circadian rhythm, cell cycle progression, chromosome segregation, apoptosis and cellular proliferation and differentiation.

Implicated in

Entity name
Cell cycle control
CK1 alpha phosphorylates the tumor suppressor p53 although it seems as if CK1 delta is the most important kinase in the regulation of p53 activity and interacts with several cellular proteins including the oncoprotein Mdm2.
Entity name
Recently is has been shown, that CK1 is involved in negatively regulating apoptosis through phosphorylation of diverse cellular proteins including the p75 tumor necrosis factor, proteins of the death-inducing signaling complex (TRAIL induced apoptosis) or Bid (FAS-mediated apoptosis).
It is thought, that CK1 mediated phosphorylation at the level of death-inducing signaling complex (DISC) leads to resistance against caspase cleavage and thereby down regulation of TRAIL (tumor necrosis-factor-related apoptosis ligand) induced apoptosis.
Furthermore, there is evidence that CK1 alpha regulates Fas-mediated apoptosis through phosphorylation of the proapoptotic Bcl2 family member Bid, which prevents caspase 8-dependant cleavage of Bid and negatively influences Fas response.
Additionally, evidence has increased that CK1 alpha modulates RXR agonist mediated apoptosis through interaction and/or phosphorylation of RXR, which prevents cytochrome C realease from the mitochondria.
Entity name
The Wnt pathway is a complex signaling cascade regulating cell proliferation and differentiation. During recent years, the significance of Wnt signaling in human cancer has been elucidated. Identification of numerous pathway components and mutations in the encoding genes finally result in stabilization and accumulation of beta-Catenin and enhanced transcription of TCF/LEF- beta-Catenin target genes.
CK1 alpha is part of the beta-Catenin destruction complex where it phosphorylates beta-Catenin at Serin 45, priming the subsequent phosphorylation of beta-Catenin by GSK3 beta. These phosphorylations mark beta-Catenin for proteasomal degradation. This is one of the central regulatory events controling the Wnt signaling-pathway.
Furthermore, CK1 has been shown to additionally regulate Wnt-signaling through phosphorylation of diverse cellular proteins including LEF-1 (lymphocyte enhancer factor-1) and beta-Catenin leading to the disruption of the LEF-1/ beta-Catenin transcription complex.
For additional information about Wnt-signaling in general, Wnt-signaling components and Wnt target genes, readers are referred to the Wnt-Homepage posted by the Nusse group.
Entity name
Neurodegenerative disorders
Deregulation of CK1 expression and activity has been linked to various diseases including neurodegenerative disorders, especially in tauophathies like Alzheimers and Parkinsons disease.


Pubmed IDLast YearTitleAuthors
14096561992Cell cycle-dependent localization of casein kinase I to mitotic spindles.Brockman JL et al
105143991999A new molecular link between the fibrillar and granulovacuolar lesions of Alzheimer's disease.Ghoshal N et al
98840211998Casein kinase I: spatial organization and positioning of a multifunctional protein kinase family.Gross SD et al
93652781997A casein kinase I isoform is required for proper cell cycle progression in the fertilized mouse oocyte.Gross SD et al
157470652005A second protein kinase CK1-mediated step negatively regulates Wnt signalling by disrupting the lymphocyte enhancer factor-1/beta-catenin complex.Hämmerlein A et al
165573932006Casein kinase-1 isoforms differentially associate with neurofibrillary and granulovacuolar degeneration lesions.Kannanayakal TJ et al
161866922005The role of the casein kinase 1 (CK1) family in different signaling pathways linked to cancer development.Knippschild U et al
129257382003A noncanonical sequence phosphorylated by casein kinase 1 in beta-catenin may play a role in casein kinase 1 targeting of important signaling proteins.Marin O et al
121763522002Casein kinase 1: a Wnt'er of disconnect.Polakis P et al
165560582005The role of Wnt signaling in cancer and stem cells.Reguart N et al

Other Information

Locus ID:

NCBI: 1452
MIM: 600505
HGNC: 2451
Ensembl: ENSG00000113712


dbSNP: 1452
ClinVar: 1452
TCGA: ENSG00000113712


Gene IDTranscript IDUniprot

Expression (GTEx)



PathwaySourceExternal ID
Wnt signaling pathwayKEGGko04310
Hedgehog signaling pathwayKEGGko04340
Wnt signaling pathwayKEGGhsa04310
Hedgehog signaling pathwayKEGGhsa04340
Diseases of signal transductionREACTOMER-HSA-5663202
Signaling by WNT in cancerREACTOMER-HSA-4791275
truncated APC mutants destabilize the destruction complexREACTOMER-HSA-4839744
APC truncation mutants have impaired AXIN bindingREACTOMER-HSA-5467337
AXIN mutants destabilize the destruction complex, activating WNT signalingREACTOMER-HSA-4839735
AXIN missense mutants destabilize the destruction complexREACTOMER-HSA-5467340
AMER1 mutants destabilize the destruction complexREACTOMER-HSA-4839748
Truncations of AMER1 destabilize the destruction complexREACTOMER-HSA-5467348
phosphorylation site mutants of CTNNB1 are not targeted to the proteasome by the destruction complexREACTOMER-HSA-4839743
S45 mutants of beta-catenin aren't phosphorylatedREACTOMER-HSA-5358751
T41 mutants of beta-catenin aren't phosphorylatedREACTOMER-HSA-5358752
S37 mutants of beta-catenin aren't phosphorylatedREACTOMER-HSA-5358749
S33 mutants of beta-catenin aren't phosphorylatedREACTOMER-HSA-5358747
Misspliced GSK3beta mutants stabilize beta-cateninREACTOMER-HSA-5339716
Signal TransductionREACTOMER-HSA-162582
Signaling by WntREACTOMER-HSA-195721
Degradation of beta-catenin by the destruction complexREACTOMER-HSA-195253
Beta-catenin phosphorylation cascadeREACTOMER-HSA-196299
TCF dependent signaling in response to WNTREACTOMER-HSA-201681
Disassembly of the destruction complex and recruitment of AXIN to the membraneREACTOMER-HSA-4641262
Signaling by HedgehogREACTOMER-HSA-5358351
Hedgehog 'off' stateREACTOMER-HSA-5610787
GLI3 is processed to GLI3R by the proteasomeREACTOMER-HSA-5610785
Degradation of GLI2 by the proteasomeREACTOMER-HSA-5610783
Hedgehog 'on' stateREACTOMER-HSA-5632684
Activation of SMOREACTOMER-HSA-5635838
Breast cancerKEGGko05224
Breast cancerKEGGhsa05224

Protein levels (Protein atlas)

Not detected


Pubmed IDYearTitleCitations
220178772011mTOR generates an auto-amplification loop by triggering the βTrCP- and CK1α-dependent degradation of DEPTOR.91
199131212009Gene-centric association signals for lipids and apolipoproteins identified via the HumanCVD BeadChip.85
211794982010High-throughput chemical screen identifies a novel potent modulator of cellular circadian rhythms and reveals CKIα as a clock regulatory kinase.76
191183832009Casein kinase 1alpha governs antigen-receptor-induced NF-kappaB activation and human lymphoma cell survival.60
168805142006Wnt-5a/Ca2+-induced NFAT activity is counteracted by Wnt-5a/Yes-Cdc42-casein kinase 1alpha signaling in human mammary epithelial cells.56
223504142012MiR-155 is a liposarcoma oncogene that targets casein kinase-1α and enhances β-catenin signaling.45
198055142009Mammalian casein kinase 1alpha and its leishmanial ortholog regulate stability of IFNAR1 and type I interferon signaling.43
192442472009Wnt-5a-CKI{alpha} signaling promotes {beta}-catenin/E-cadherin complex formation and intercellular adhesion in human breast epithelial cells.42
197590232009CK1alpha plays a central role in mediating MDM2 control of p53 and E2F-1 protein stability.38
255005332014Phosphorylation of LRRK2 by casein kinase 1α regulates trans-Golgi clustering via differential interaction with ARHGEF7.36


Max Doerfel ; Otmar Huber

CSNK1A1 (casein kinase 1, alpha 1)

Atlas Genet Cytogenet Oncol Haematol. 2008-05-01

Online version: http://atlasgeneticsoncology.org/gene/40168/csnk1a1