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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)

Identity

Alias_namescasein kinase 1
Alias_symbol (synonym)CK1
CK1a
CK1alpha
CKIa
CKIalpha
Other aliasCKI-alpha
EC 2.7.11.1
HLCDGP1
PRO2975
HGNC (Hugo) CSNK1A1
LocusID (NCBI) 1452
Atlas_Id 40168
Location 5q32  [Link to chromosome band 5q32]
Location_base_pair Starts at 149495894 and ends at 149551552 bp from pter ( according to hg19-Feb_2009)  [Mapping CSNK1A1.png]
Fusion genes
(updated 2016)
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.

DNA/RNA

 
  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.

Protein

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

Note
  
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.
  

Bibliography

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
 

Citation

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 ]
On line version : http://AtlasGeneticsOncology.org/Genes/CSNK1A1ID40168ch5q32.html


External links

Nomenclature
HGNC (Hugo)CSNK1A1   2451
Cards
AtlasCSNK1A1ID40168ch5q32
Entrez_Gene (NCBI)CSNK1A1  1452  casein kinase 1 alpha 1
AliasesCK1; CK1a; CKIa; HEL-S-77p; 
HLCDGP1; PRO2975
GeneCards (Weizmann)CSNK1A1
Ensembl hg19 (Hinxton)ENSG00000113712 [Gene_View]
Ensembl hg38 (Hinxton)ENSG00000113712 [Gene_View]  chr5:149495894-149551552 [Contig_View]  CSNK1A1 [Vega]
ICGC DataPortalENSG00000113712
TCGA cBioPortalCSNK1A1
AceView (NCBI)CSNK1A1
Genatlas (Paris)CSNK1A1
WikiGenes1452
SOURCE (Princeton)CSNK1A1
Genetics Home Reference (NIH)CSNK1A1
Genomic and cartography
GoldenPath hg38 (UCSC)CSNK1A1  -     chr5:149495894-149551552 -  5q32   [Description]    (hg38-Dec_2013)
GoldenPath hg19 (UCSC)CSNK1A1  -     5q32   [Description]    (hg19-Feb_2009)
EnsemblCSNK1A1 - 5q32 [CytoView hg19]  CSNK1A1 - 5q32 [CytoView hg38]
Mapping of homologs : NCBICSNK1A1 [Mapview hg19]  CSNK1A1 [Mapview hg38]
OMIM600505   
Gene and transcription
Genbank (Entrez)###############################################################################################################################################################################################################################################################
RefSeq transcript (Entrez)NM_001025105 NM_001271741 NM_001271742 NM_001892
RefSeq genomic (Entrez)
Consensus coding sequences : CCDS (NCBI)CSNK1A1
Cluster EST : UnigeneHs.712555 [ NCBI ]
CGAP (NCI)Hs.712555
Alternative Splicing GalleryENSG00000113712
Gene ExpressionCSNK1A1 [ NCBI-GEO ]   CSNK1A1 [ EBI - ARRAY_EXPRESS ]   CSNK1A1 [ SEEK ]   CSNK1A1 [ MEM ]
Gene Expression Viewer (FireBrowse)CSNK1A1 [ Firebrowse - Broad ]
SOURCE (Princeton)Expression in : [Datasets]   [Normal Tissue Atlas]  [carcinoma Classsification]  [NCI60]
GenevisibleExpression in : [tissues]  [cell-lines]  [cancer]  [perturbations]  
BioGPS (Tissue expression)1452
GTEX Portal (Tissue expression)CSNK1A1
Protein : pattern, domain, 3D structure
UniProt/SwissProtP48729   [function]  [subcellular_location]  [family_and_domains]  [pathology_and_biotech]  [ptm_processing]  [expression]  [interaction]
NextProtP48729  [Sequence]  [Exons]  [Medical]  [Publications]
With graphics : InterProP48729
Splice isoforms : SwissVarP48729
Catalytic activity : Enzyme2.7.11.1 [ Enzyme-Expasy ]   2.7.11.12.7.11.1 [ IntEnz-EBI ]   2.7.11.1 [ BRENDA ]   2.7.11.1 [ KEGG ]   
PhosPhoSitePlusP48729
Domaine pattern : Prosite (Expaxy)PROTEIN_KINASE_ATP (PS00107)    PROTEIN_KINASE_DOM (PS50011)    PROTEIN_KINASE_ST (PS00108)   
Domains : Interpro (EBI)Kinase-like_dom    Prot_kinase_dom    Protein_kinase_ATP_BS    Ser/Thr_kinase_AS   
Domain families : Pfam (Sanger)Pkinase (PF00069)   
Domain families : Pfam (NCBI)pfam00069   
Domain families : Smart (EMBL)S_TKc (SM00220)  
Conserved Domain (NCBI)CSNK1A1
DMDM Disease mutations1452
Blocks (Seattle)CSNK1A1
PDB (SRS)5FQD   
PDB (PDBSum)5FQD   
PDB (IMB)5FQD   
PDB (RSDB)5FQD   
Structural Biology KnowledgeBase5FQD   
SCOP (Structural Classification of Proteins)5FQD   
CATH (Classification of proteins structures)5FQD   
SuperfamilyP48729
Human Protein AtlasENSG00000113712
Peptide AtlasP48729
HPRD02739
IPIIPI00183400   IPI00448798   IPI00963961   IPI00292086   IPI00978576   IPI00966927   IPI00964427   IPI00965679   IPI00976381   
Protein Interaction databases
DIP (DOE-UCLA)P48729
IntAct (EBI)P48729
FunCoupENSG00000113712
BioGRIDCSNK1A1
STRING (EMBL)CSNK1A1
ZODIACCSNK1A1
Ontologies - Pathways
QuickGOP48729
Ontology : AmiGOcondensed chromosome kinetochore  protein kinase activity  protein kinase activity  protein serine/threonine kinase activity  protein serine/threonine kinase activity  protein serine/threonine kinase activity  protein binding  ATP binding  centrosome  cytosol  cytosol  mRNA cleavage and polyadenylation specificity factor complex  cilium  protein phosphorylation  phagocytosis  Golgi organization  cell cycle  signal transduction  cell surface receptor signaling pathway  regulation of cell shape  membrane  Wnt signaling pathway  Wnt signaling pathway  kinase activity  nuclear speck  peptidyl-serine phosphorylation  peptidyl-serine phosphorylation  beta-catenin destruction complex  positive regulation of proteasomal ubiquitin-dependent protein catabolic process  proteasome-mediated ubiquitin-dependent protein catabolic process  keratin filament  intermediate filament cytoskeleton organization  cell division  negative regulation of canonical Wnt signaling pathway  regulation of GTP binding  beta-catenin destruction complex assembly  beta-catenin destruction complex disassembly  
Ontology : EGO-EBIcondensed chromosome kinetochore  protein kinase activity  protein kinase activity  protein serine/threonine kinase activity  protein serine/threonine kinase activity  protein serine/threonine kinase activity  protein binding  ATP binding  centrosome  cytosol  cytosol  mRNA cleavage and polyadenylation specificity factor complex  cilium  protein phosphorylation  phagocytosis  Golgi organization  cell cycle  signal transduction  cell surface receptor signaling pathway  regulation of cell shape  membrane  Wnt signaling pathway  Wnt signaling pathway  kinase activity  nuclear speck  peptidyl-serine phosphorylation  peptidyl-serine phosphorylation  beta-catenin destruction complex  positive regulation of proteasomal ubiquitin-dependent protein catabolic process  proteasome-mediated ubiquitin-dependent protein catabolic process  keratin filament  intermediate filament cytoskeleton organization  cell division  negative regulation of canonical Wnt signaling pathway  regulation of GTP binding  beta-catenin destruction complex assembly  beta-catenin destruction complex disassembly  
Pathways : BIOCARTANFAT and Hypertrophy of the heart (Transcription in the broken heart) [Genes]   
Pathways : KEGGWnt signaling pathway    Hedgehog signaling pathway   
REACTOMEP48729 [protein]
REACTOME PathwaysR-HSA-5635838 [pathway]   
NDEx NetworkCSNK1A1
Atlas of Cancer Signalling NetworkCSNK1A1
Wikipedia pathwaysCSNK1A1
Orthology - Evolution
OrthoDB1452
GeneTree (enSembl)ENSG00000113712
Phylogenetic Trees/Animal Genes : TreeFamCSNK1A1
HOVERGENP48729
HOGENOMP48729
Homologs : HomoloGeneCSNK1A1
Homology/Alignments : Family Browser (UCSC)CSNK1A1
Gene fusions - Rearrangements
Polymorphisms : SNP and Copy number variants
NCBI Variation ViewerCSNK1A1 [hg38]
dbSNP Single Nucleotide Polymorphism (NCBI)CSNK1A1
dbVarCSNK1A1
ClinVarCSNK1A1
1000_GenomesCSNK1A1 
Exome Variant ServerCSNK1A1
ExAC (Exome Aggregation Consortium)CSNK1A1 (select the gene name)
Genetic variants : HAPMAP1452
Genomic Variants (DGV)CSNK1A1 [DGVbeta]
DECIPHERCSNK1A1 [patients]   [syndromes]   [variants]   [genes]  
CONAN: Copy Number AnalysisCSNK1A1 
Mutations
ICGC Data PortalCSNK1A1 
TCGA Data PortalCSNK1A1 
Broad Tumor PortalCSNK1A1
OASIS PortalCSNK1A1 [ Somatic mutations - Copy number]
Somatic Mutations in Cancer : COSMICCSNK1A1  [overview]  [genome browser]  [tissue]  [distribution]  
Mutations and Diseases : HGMDCSNK1A1
LOVD (Leiden Open Variation Database)Whole genome datasets
LOVD (Leiden Open Variation Database)LOVD - Leiden Open Variation Database
LOVD (Leiden Open Variation Database)LOVD 3.0 shared installation
BioMutasearch CSNK1A1
DgiDB (Drug Gene Interaction Database)CSNK1A1
DoCM (Curated mutations)CSNK1A1 (select the gene name)
CIViC (Clinical Interpretations of Variants in Cancer)CSNK1A1 (select a term)
intoGenCSNK1A1
NCG5 (London)CSNK1A1
Cancer3DCSNK1A1(select the gene name)
Impact of mutations[PolyPhen2] [SIFT Human Coding SNP] [Buck Institute : MutDB] [Mutation Assessor] [Mutanalyser]
Diseases
OMIM600505   
Orphanet
MedgenCSNK1A1
Genetic Testing Registry CSNK1A1
NextProtP48729 [Medical]
TSGene1452
GENETestsCSNK1A1
Target ValidationCSNK1A1
Huge Navigator CSNK1A1 [HugePedia]
snp3D : Map Gene to Disease1452
BioCentury BCIQCSNK1A1
ClinGenCSNK1A1
Clinical trials, drugs, therapy
Chemical/Protein Interactions : CTD1452
Chemical/Pharm GKB GenePA26951
Clinical trialCSNK1A1
Miscellaneous
canSAR (ICR)CSNK1A1 (select the gene name)
Probes
Litterature
PubMed134 Pubmed reference(s) in Entrez
GeneRIFsGene References Into Functions (Entrez)
CoreMineCSNK1A1
EVEXCSNK1A1
GoPubMedCSNK1A1
iHOPCSNK1A1
REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed

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indexed on : Tue Aug 1 17:23:48 CEST 2017

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