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CTNNB1 (Catenin, beta-1)

Identity

Other namesCadherin-associated protein, beta
HGNC (Hugo) CTNNB1
Location 3p22-p21.3
Location_base_pair Starts at 41215946 and ends at 41256943 bp from pter ( according to hg18-Mar_2006)  [Mapping]
 
  CTNNB1 (3p22) - Courtesy Mariano Rocchi, Resources for Molecular Cytogenetics. Laboratories willing to validate the probes are welcome : contact rocchi@biologia.uniba.it

DNA/RNA

 
Description The gene encompasses 23.2kb of DNA ; 16 exons (the first is non-coding).
Transcription 3362 nucleotides mRNA ; 2343 bp open reading frame. Alternative splicing within exon 16 produces a splice variant that is 159 bp shorter in the 3' untranslated region.

Protein

 
Description 781 amino acids ; 92 kDa protein. Can be phosphorylated ; contains from N-term to C-term, a phosphorylation site by the serine-threonine glycogen synthase kinase -3b(GSK-3b), an a-catenin binding site, 13 armadillo repeats and a transactivating domain.
Expression Widely expressed.
Localisation Cytoplasm and nucleus
Function Important functions in the E-cadherin-mediated cell-cell adhesion system and also as a dowstream signaling molecule in the Wnt pathway. Cytoplasmic accumulation of b catenin allows it to translocate to the nucleus to form complexes with transcription factors of the T cell factor-lymphoid enhancer factor (Tcf-Lef) family. b-catenin is assumed to transactivate mostly unknown target genes, which may stimulate cell proliferation (acts as an oncogene) or inhibit apoptosis. The b-catenin level in the cell is regulated by its association with the adenomatous polyposis coli ( APC) tumor suppressor protein, axin and GSK-3b. Phosphorylation of b-catenin by the APC-axin-GSK-3b complex leads to its degradation by the ubiquitin-proteasome system.
Homology The b-catenin protein shares 70 % amino acid identity with both plakoglobin (intracellular junction in desmosomes) and the product of the Drosphila segment polarity gene "armadillo".

Mutations

Somatic Two mechanisms underlying the increase in b-catenin levels by stabilizing b-catenin are known. One is inactivating mutation in the APC gene, the other is activating mutation at the GSK-3b phosphorylation sites within exon 3 of the b-catenin gene.
b-catenin plays a key role in the development of colorectal cancer and has been found mutated in colorectal cancer cell lines. b-catenin aberration is a frequent event in the development of hepatocellular carcinoma and may facilitate its development in the course of chronic hepatitis. b-catenin has also been found mutated in hepatoblastoma, ovarian carcinoma, medulloblastoma, pilomatricoma as well as in melanoma cell lines.

External links

Nomenclature
HGNC (Hugo)CTNNB1   2514
Entrez_Gene (NCBI)CTNNB1  1499  catenin (cadherin-associated protein), beta 1, 88kDa
Cards
AtlasCTNNB1ID71
GeneCards (Weizmann)CTNNB1
Ensembl (Hinxton)ENSG00000168036 [Gene_View]  CTNNB1 [Vega]
AceView (NCBI)CTNNB1
Genatlas (Paris)CTNNB1
euGene (Indiana)1499
SOURCE (Stanford)NM_001098209 NM_001098210 NM_001904
Genomic and cartography
GoldenPath (UCSC)CTNNB1  -     chr3:41215946-41256943 +  3p21   [Description]    (hg18-Mar_2006)
EnsemblCTNNB1 - 3p21 [CytoView]
Mapping of homologs : NCBICTNNB1 [Mapview]
OMIM114550   116806   132600   155255   167000   
Gene and transcription
Gene : Genbank (Entrez)AB062292 AB451264 AB451392 AK095242 AK289932
Reference sequence (RefSeq transcript) :SRSNM_001098209 NM_001098210 NM_001904
Reference transcript : EntrezNM_001098209 NM_001098210 NM_001904
RefSeq genomic : SRSAC_000046 AC_000135 NC_000003 NT_022517 NW_001838877 NW_921651
RefSeq genomic : EntrezAC_000046 AC_000135 NC_000003 NT_022517 NW_001838877 NW_921651
Consensus coding sequences : CCDS NCBICTNNB1
Cluster EST : UnigeneHs.476018 [ SRS ] Hs.476018 [ NCBI ]
Alternative Splicing : Fast-db (Paris)4557
Protein : pattern, domain, 3D structure
Protein : UniProt/SwissProtP35222 (SRS) P35222 (Expasy) P35222 (Uniprot)
With graphics : InterProP35222
Splice isoforms : VarSplice FASTAP35222(VarSplice FASTA)
Domaine pattern : Prosite (SRS)ARM_REPEAT (PS50176)   
Domain pattern : Prosite (Expaxy)ARM_REPEAT (PS50176)   
Domains : Interpro (SRS)ARM-like    Armadillo    Beta-catenin    HEAT   
Domains : Interpro (EBI)ARM-like    Armadillo    Beta-catenin    HEAT   
Related proteins : CluSTrP35222
Domain families : Pfam SRSArm (PF00514)    HEAT (PF02985)   
Domain families : Pfam SangerArm (PF00514)    HEAT (PF02985)   
Domain families : Pfam NCBIpfam00514    pfam02985   
Domain families : Smart EMBLARM (SM00185)
Blocks (Seattle)P35222
Crystal structure of protein : PDB SRS1G3J    1JDH    1JPW    1LUJ    1P22    1QZ7    1T08    1TH1    2G57    2GL7    2Z6H   
Crystal structure of protein : PDBSum1G3J    1JDH    1JPW    1LUJ    1P22    1QZ7    1T08    1TH1    2G57    2GL7    2Z6H   
Crystal structure of protein : IMB1G3J    1JDH    1JPW    1LUJ    1P22    1QZ7    1T08    1TH1    2G57    2GL7    2Z6H   
Crystal structure of protein : PDB RSDB1G3J    1JDH    1JPW    1LUJ    1P22    1QZ7    1T08    1TH1    2G57    2GL7    2Z6H   
HPRD00286
Protein Interaction databases
DIP (DOE-UCLA)P35222
IntAct (EBI)P35222
Polymorphism : SNP, mutations, diseases
Single Nucleotide Polymorphism (SNP) : dbSNP NCBICTNNB1
SNP : GeneSNP UtahCTNNB1
SNP : HGBaseCTNNB1
Genetic variants : HAPMAPCTNNB1
Somatic Mutations in Cancer : COSMICCTNNB1 
Mutations and Diseases : HGMDCTNNB1
Hereditary diseases : OMIM114550    116806    132600    155255    167000   
Hereditary diseases : GENETests114550    116806    132600    155255    167000   
Diseases : Genetic AssociationCTNNB1
General knowledge
Homologs : HomoloGeneCTNNB1
Homology/Alignments : Family Browser UCSCCTNNB1
Phylogenetic Trees/Animal Genes : TreeFamCTNNB1
Chemical/Protein Interactions : CTD1499
Keywords Ontology : AmiGOnegative regulation of transcription from RNA polymerase II promoter  skeletal system development  patterning of blood vessels  gastrulation with mouth forming second  endoderm formation  cell fate specification  cell fate determination  endodermal cell fate commitment  epithelial to mesenchymal transition  chromatin binding  double-stranded DNA binding  transcription factor activity  transcription coactivator activity  signal transducer activity  membrane fraction  nucleus  transcription factor complex  cytoplasm  centrosome  cytosol  cytoskeleton  plasma membrane  fascia adherens  apoptosis  cell-matrix adhesion  synaptic transmission  ectoderm development  heart development  protein C-terminus binding  transcription factor binding  anterior/posterior axis specification  dorsal/ventral axis specification  proximal/distal pattern formation  positive regulation of specific transcription from RNA polymerase II promoter  basolateral plasma membrane  lateral plasma membrane  morphogenesis of embryonic epithelium  cell-cell adhesion  catenin complex  kinase binding  protein phosphatase binding  Z disc  lamellipodium  hemopoiesis  lung development  androgen receptor signaling pathway  positive regulation of epithelial cell differentiation  beta-catenin destruction complex  forebrain development  regulation of centriole-centriole cohesion  pancreas development  microvillus membrane  negative regulation of chondrocyte differentiation  Axin-APC-beta-catenin-GSK3B complex  embryonic hindlimb morphogenesis  embryonic arm morphogenesis  regulation of cell proliferation  phosphate binding  odontogenesis of dentine-containing tooth  embryonic digit morphogenesis  apical junction complex  apical part of cell  alpha-catenin binding  cadherin binding  bone resorption  positive regulation of osteoblast differentiation  negative regulation of osteoclast differentiation  SMAD binding  cell maturation  synaptic vesicle transport  camera-type eye morphogenesis  androgen receptor binding  synapse organization  Wnt receptor signaling pathway through beta-catenin  
Keywords Ontology : EGO-EBInegative regulation of transcription from RNA polymerase II promoter  skeletal system development  patterning of blood vessels  gastrulation with mouth forming second  endoderm formation  cell fate specification  cell fate determination  endodermal cell fate commitment  epithelial to mesenchymal transition  chromatin binding  double-stranded DNA binding  transcription factor activity  transcription coactivator activity  signal transducer activity  membrane fraction  nucleus  transcription factor complex  cytoplasm  centrosome  cytosol  cytoskeleton  plasma membrane  fascia adherens  apoptosis  cell-matrix adhesion  synaptic transmission  ectoderm development  heart development  protein C-terminus binding  transcription factor binding  anterior/posterior axis specification  dorsal/ventral axis specification  proximal/distal pattern formation  positive regulation of specific transcription from RNA polymerase II promoter  basolateral plasma membrane  lateral plasma membrane  morphogenesis of embryonic epithelium  cell-cell adhesion  catenin complex  kinase binding  protein phosphatase binding  Z disc  lamellipodium  hemopoiesis  lung development  androgen receptor signaling pathway  positive regulation of epithelial cell differentiation  beta-catenin destruction complex  forebrain development  regulation of centriole-centriole cohesion  pancreas development  microvillus membrane  negative regulation of chondrocyte differentiation  Axin-APC-beta-catenin-GSK3B complex  embryonic hindlimb morphogenesis  embryonic arm morphogenesis  regulation of cell proliferation  phosphate binding  odontogenesis of dentine-containing tooth  embryonic digit morphogenesis  apical junction complex  apical part of cell  alpha-catenin binding  cadherin binding  bone resorption  positive regulation of osteoblast differentiation  negative regulation of osteoclast differentiation  SMAD binding  cell maturation  synaptic vesicle transport  camera-type eye morphogenesis  androgen receptor binding  synapse organization  Wnt receptor signaling pathway through beta-catenin  
Pathways : BIOCARTAALK in cardiac myocytes [Genes]    Cell to Cell Adhesion Signaling [Genes]    Inactivation of Gsk3 by AKT causes accumulation of b-catenin in Alveolar Macrophages [Genes]    Multi-step Regulation of Transcription by Pitx2 [Genes]    Presenilin action in Notch and Wnt signaling [Genes]    Trefoil Factors Initiate Mucosal Healing [Genes]    WNT Signaling Pathway [Genes]   
Pathways : KEGGWnt signaling pathwayFocal adhesionAdherens junctionTight junctionLeukocyte transendothelial migrationColorectal cancer
Other databases
Probes
ProbeCancer Cytogenetics (Bari)
Probes : ImagenesCTNNB1 Related clones (RZPD - Berlin)
Literature
PubMed499 Pubmed reference(s) in Entrez
PubGeneCTNNB1

Bibliography

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PMID 11282485
 
The transcriptional factor Tcf-4 contains different binding sites for beta-catenin and plakoglobin.
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PMID 11711551
 
Oncogenic beta-catenin and MMP-7 (matrilysin) cosegregate in late-stage clinical colon cancer.
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PMID 11781281
 
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Laboratory investigation; a journal of technical methods and pathology. 2002 ; 82 (1) : 97-103.
PMID 11796830
 
Frizzled-10, up-regulated in primary colorectal cancer, is a positive regulator of the WNT - beta-catenin - TCF signaling pathway.
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PMID 11786918
 
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Contributor(s)

Written03-2002Brigitte Debuire, Antoinette Lemoine and Raphael Saffroy
Service de Biochimie et Biologie moléculaire, Hôpital Universitaire Paul Brousse, UPRES 1596-Faculté de Médecine Paris-Sud, 14 avenue Paul Vaillant Couturier, 94804 Villejuif Cedex, France

Citation

This paper should be referenced as such :
Debuire B, Lemoine A, Saffroy R . CTNNB1 (Catenin, beta-1). Atlas Genet Cytogenet Oncol Haematol. March 2002 .
URL : http://AtlasGeneticsOncology.org/Genes/CTNNB1ID71.html

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indexed on : Sat Jun 27 16:39:04 CEST 2009

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