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CSNK1A1 (casein kinase 1, alpha 1)

Written2008-05Max Doerfel, Otmar Huber
Department of Laboratory Medicine, Pathobiochemistry, Charite - Universitatsmedizin Berlin, Campus Benjamin Franklin, Hindenburgdamm 30, 12203 Berlin, Germany

(Note : for Links provided by Atlas : click)


Alias (NCBI)CK1
HGNC Alias symbCK1
HGNC Alias nameclock regulator kinase
HGNC Previous namecasein kinase 1, alpha 1
LocusID (NCBI) 1452
Atlas_Id 40168
Location 5q32  [Link to chromosome band 5q32]
Location_base_pair Starts at 149492982 and ends at 149551439 bp from pter ( according to GRCh38/hg38-Dec_2013)  [Mapping CSNK1A1.png]
Fusion genes
(updated 2017)
Data from Atlas, Mitelman, Cosmic Fusion, Fusion Cancer, TCGA fusion databases with official HUGO symbols (see references in chromosomal bands)
CSNK1A1 (5q32)::CSNK1A1 (5q32)CSNK1A1 (5q32)::LAMTOR2 (1q22)CSNK1A1 (5q32)::TUBB2A (6p25.2)
CSNK1A1 (5q32)::ZBTB5 (9p13.2)
Note Member of the casein kinase family of serine/threonine protein kinases.


  Diagram of hCK1 alpha gene. Exons for both isoforms are presented as red boxes, with exon mumbers at the bottom.
Description According to Entrez-Gene, CNK1 alpha1 gene maps to NC_000005.8.
Transcription 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.


Note 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.
Description 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.
Localisation The protein kinase CK1 alpha is ubiquitously expressed in all tissues and detected in all cellular compartments.
Function 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 Cell cycle control
Note 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 Apoptosis
Note 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 Wnt signaling
Note 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 Neurodegenerative disorders
Note Deregulation of CK1 expression and activity has been linked to various diseases including neurodegenerative disorders, especially in tauophathies like Alzheimer's and Parkinson's disease.


Cell cycle-dependent localization of casein kinase I to mitotic spindles.
Brockman JL, Gross SD, Sussman MR, Anderson RA.
Proc Natl Acad Sci U S A. 1992 Oct 15;89(20):9454-8.
PMID 1409656
A new molecular link between the fibrillar and granulovacuolar lesions of Alzheimer's disease.
Ghoshal N, Smiley JF, DeMaggio AJ, Hoekstra MF, Cochran EJ, Binder LI, Kuret J.
Am J Pathol. 1999 Oct;155(4):1163-72.
PMID 10514399
Casein kinase I: spatial organization and positioning of a multifunctional protein kinase family.
Gross SD, Anderson RA.
Cell Signal. 1998 Nov;10(10):699-711.
PMID 9884021
A casein kinase I isoform is required for proper cell cycle progression in the fertilized mouse oocyte.
Gross SD, Simerly C, Schatten G, Anderson RA.
J Cell Sci. 1997 Dec;110 ( Pt 24):3083-90.
PMID 9365278
A second protein kinase CK1-mediated step negatively regulates Wnt signalling by disrupting the lymphocyte enhancer factor-1/beta-catenin complex.
Hammerlein A, Weiske J, Huber O.
Cell Mol Life Sci. 2005 Mar;62(5):606-18.
PMID 15747065
Casein kinase-1 isoforms differentially associate with neurofibrillary and granulovacuolar degeneration lesions.
Kannanayakal TJ, Tao H, Vandre DD, Kuret J.
Acta Neuropathol. 2006 May;111(5):413-21. Epub 2006 Mar 24.
PMID 16557393
The role of the casein kinase 1 (CK1) family in different signaling pathways linked to cancer development.
Knippschild U, Wolff S, Giamas G, Brockschmidt C, Wittau M, Wurl PU, Eismann T, Stoter M.
Onkologie. 2005 Oct;28(10):508-14. Epub 2005 Sep 19.
PMID 16186692
A 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, Bustos VH, Cesaro L, Meggio F, Pagano MA, Antonelli M, Allende CC, Pinna LA, Allende JE.
Proc Natl Acad Sci U S A. 2003 Sep 2;100(18):10193-200. Epub 2003 Aug 18.
PMID 12925738
Casein kinase 1: a Wnt'er of disconnect.
Polakis P.
Curr Biol. 2002 Jul 23;12(14):R499-R501.
PMID 12176352
The role of Wnt signaling in cancer and stem cells.
Reguart N, He B, Taron M, You L, Jablons DM, Rosell R.
Future Oncol. 2005 Dec;1(6):787-97.
PMID 16556058


This paper should be referenced as such :
Doerfel, M ; Huber, O
CSNK1A1 (casein kinase 1, alpha 1)
Atlas Genet Cytogenet Oncol Haematol. 2009;13(4):260-262.
Free journal version : [ pdf ]   [ DOI ]

External links

HGNC (Hugo)CSNK1A1   2451
Entrez_Gene (NCBI)CSNK1A1    casein kinase 1 alpha 1
AliasesCK1; CK1a; CKIa; HEL-S-77p; 
GeneCards (Weizmann)CSNK1A1
Ensembl hg19 (Hinxton)ENSG00000113712 [Gene_View]
Ensembl hg38 (Hinxton)ENSG00000113712 [Gene_View]  ENSG00000113712 [Sequence]  chr5:149492982-149551439 [Contig_View]  CSNK1A1 [Vega]
ICGC DataPortalENSG00000113712
TCGA cBioPortalCSNK1A1
Genatlas (Paris)CSNK1A1
SOURCE (Princeton)CSNK1A1
Genetics Home Reference (NIH)CSNK1A1
Genomic and cartography
GoldenPath hg38 (UCSC)CSNK1A1  -     chr5:149492982-149551439 -  5q32   [Description]    (hg38-Dec_2013)
GoldenPath hg19 (UCSC)CSNK1A1  -     5q32   [Description]    (hg19-Feb_2009)
GoldenPathCSNK1A1 - 5q32 [CytoView hg19]  CSNK1A1 - 5q32 [CytoView hg38]
Genome Data Viewer NCBICSNK1A1 [Mapview hg19]  
Gene and transcription
Genbank (Entrez)AF119911 AF218004 AF447582 AK293761 AK294099
RefSeq transcript (Entrez)NM_001025105 NM_001271741 NM_001271742 NM_001892
Consensus coding sequences : CCDS (NCBI)CSNK1A1
Gene ExpressionCSNK1A1 [ NCBI-GEO ]   CSNK1A1 [ EBI - ARRAY_EXPRESS ]   CSNK1A1 [ SEEK ]   CSNK1A1 [ MEM ]
Gene Expression Viewer (FireBrowse)CSNK1A1 [ Firebrowse - Broad ]
GenevisibleExpression of CSNK1A1 in : [tissues]  [cell-lines]  [cancer]  [perturbations]  
BioGPS (Tissue expression)1452
GTEX Portal (Tissue expression)CSNK1A1
Human Protein AtlasENSG00000113712-CSNK1A1 [pathology]   [cell]   [tissue]
Protein : pattern, domain, 3D structure
Domain families : Pfam (Sanger)
Domain families : Pfam (NCBI)
Conserved Domain (NCBI)CSNK1A1
Human Protein Atlas [tissue]ENSG00000113712-CSNK1A1 [tissue]
Protein Interaction databases
Complex Portal (EBI) CPX-99 Beta-catenin destruction core complex, variant 2
CPX-107 Beta-catenin destruction core complex, variant 5
CPX-109 Beta-catenin destruction core complex, variant 1
CPX-441 Beta-catenin destruction core complex, variant 7
CPX-442 Beta-catenin destruction core complex, variant 6
CPX-443 Beta-catenin destruction core complex, variant 8
CPX-439 Beta-catenin destruction core complex, variant 3
CPX-440 Beta-catenin destruction core complex, variant 4
Ontologies - Pathways
PubMed201 Pubmed reference(s) in Entrez
GeneRIFsGene References Into Functions (Entrez)
REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed

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