CTNNB1 (Catenin, beta-1)

2002-03-01   Brigitte Debuire  , Antoinette Lemoine  , 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

Identity

HGNC
CTNNB1
LOCATION
3p22.1
IMAGE
Atlas Image
LEGEND
CTNNB1 (3p22) - Courtesy Mariano Rocchi, Resources for Molecular Cytogenetics.
LOCUSID
1499
ALIAS
CTNNB,EVR7,MRD19,NEDSDV,armadillo
FUSION GENES
Show Gene Fusions

DNA/RNA

Atlas Image

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.

Proteins

Atlas Image

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.

Implicated in

Article Bibliography

Pubmed IDLast YearTitleAuthors
92337891997beta-catenin is a target for the ubiquitin-proteasome pathway.Aberle H et al
77806641995Yeast artificial chromosome cloning of the beta-catenin locus on human chromosome 3p21-22.Bailey A et al
95548521998Functional interaction of an axin homolog, conductin, with beta-catenin, APC, and GSK3beta.Behrens J et al
87571361996Functional interaction of beta-catenin with the transcription factor LEF-1.Behrens J et al
103984361999Beta-catenin accumulation and mutation of the CTNNB1 gene in hepatoblastoma.Bläker H et al
101923931999A common human skin tumour is caused by activating mutations in beta-catenin.Chan EF et al
103622591999The metalloproteinase matrilysin is a target of beta-catenin transactivation in intestinal tumors.Crawford HC et al
95019801998Nuclear localization signal-independent and importin/karyopherin-independent nuclear import of beta-catenin.Fagotto F et al
112824852001Frequent beta-catenin aberration in human hepatocellular carcinoma.Fujie H et al
85733371995Signal transduction of beta-catenin.Gumbiner BM et al
105451051999Intestinal polyposis in mice with a dominant stable mutation of the beta-catenin gene.Harada N et al
96016411998Downregulation of beta-catenin by human Axin and its association with the APC tumor suppressor, beta-catenin and GSK3 beta.Hart MJ et al
106663722000APC mutations in sporadic medulloblastomas.Huang H et al
88922281996Nuclear localization of beta-catenin by interaction with transcription factor LEF-1.Huber O et al
94827341998Axin, a negative regulator of the Wnt signaling pathway, forms a complex with GSK-3beta and beta-catenin and promotes GSK-3beta-dependent phosphorylation of beta-catenin.Ikeda S et al
92942101997Beta-catenin mutations in cell lines established from human colorectal cancers.Ilyas M et al
95004651998Activation of the beta-catenin gene by interstitial deletions involving exon 3 in primary colorectal carcinomas without adenomatous polyposis coli mutations.Iwao K et al
99270291999Childhood hepatoblastomas frequently carry a mutated degradation targeting box of the beta-catenin gene.Koch A et al
109530282000Gastrin is a target of the beta-catenin/TCF-4 growth-signaling pathway in a model of intestinal polyposis.Koh TJ et al
78290881994Localization of the human beta-catenin gene (CTNNB1) to 3p21: a region implicated in tumor development.Kraus C et al
104356291999Beta-catenin mutations in hepatocellular carcinoma correlate with a low rate of loss of heterozygosity.Legoix P et al
110170672000Mutations in AXIN2 cause colorectal cancer with defective mismatch repair by activating beta-catenin/TCF signalling.Liu W et al
117115512002The transcriptional factor Tcf-4 contains different binding sites for beta-catenin and plakoglobin.Miravet S et al
90654021997Activation of beta-catenin-Tcf signaling in colon cancer by mutations in beta-catenin or APC.Morin PJ et al
88388051996Genomic organization of the human beta-catenin gene (CTNNB1).Nollet F et al
117812812002Oncogenic beta-catenin and MMP-7 (matrilysin) cosegregate in late-stage clinical colon cancer.Ougolkov AV et al
90654031997Stabilization of beta-catenin by genetic defects in melanoma cell lines.Rubinfeld B et al
103910901999Mutational analysis of beta-catenin gene in Japanese ovarian carcinomas: frequent mutations in endometrioid carcinomas.Sagae S et al
117968302002Possible association between higher beta-catenin mRNA expression and mutated beta-catenin in sporadic desmoid tumors: real-time semiquantitative assay by TaqMan polymerase chain reaction.Saito T et al
103189161999The cyclin D1 gene is a target of the beta-catenin/LEF-1 pathway.Shtutman M et al
95157951998Mutational analysis of the APC/beta-catenin/Tcf pathway in colorectal cancer.Sparks AB et al
82595191993Association of the APC tumor suppressor protein with catenins.Su LK et al
117869182002Frizzled-10, up-regulated in primary colorectal cancer, is a positive regulator of the WNT - beta-catenin - TCF signaling pathway.Terasaki H et al
85217211995The gene for the APC-binding protein beta-catenin (CTNNB1) maps to chromosome 3p22, a region frequently altered in human malignancies.Trent JM et al
96717671998Somatic mutations of the beta-catenin gene are frequent in mouse and human hepatocellular carcinomas.de La Coste A et al
77367931995Assignment of the human beta-catenin gene (CTNNB1) to 3p22-->p21.3 by fluorescence in situ hybridization.van Hengel J et al

Other Information

Locus ID:

NCBI: 1499
MIM: 116806
HGNC: 2514
Ensembl: ENSG00000168036

Variants:

dbSNP: 1499
ClinVar: 1499
TCGA: ENSG00000168036
COSMIC: CTNNB1

RNA/Proteins

Gene IDTranscript IDUniprot
ENSG00000168036ENST00000349496P35222
ENSG00000168036ENST00000349496A0A024R2Q3
ENSG00000168036ENST00000396183P35222
ENSG00000168036ENST00000396183A0A024R2Q3
ENSG00000168036ENST00000396185P35222
ENSG00000168036ENST00000396185A0A024R2Q3
ENSG00000168036ENST00000405570P35222
ENSG00000168036ENST00000405570A0A024R2Q3
ENSG00000168036ENST00000426215C9IZ65
ENSG00000168036ENST00000431914P35222
ENSG00000168036ENST00000431914A0A024R2Q3
ENSG00000168036ENST00000433400P35222
ENSG00000168036ENST00000433400A0A024R2Q3
ENSG00000168036ENST00000441708P35222
ENSG00000168036ENST00000441708A0A024R2Q3
ENSG00000168036ENST00000450969P35222
ENSG00000168036ENST00000450969A0A024R2Q3
ENSG00000168036ENST00000453024B4DGU4
ENSG00000168036ENST00000471014A0A2R8YG06
ENSG00000168036ENST00000642248P35222
ENSG00000168036ENST00000642248A0A024R2Q3
ENSG00000168036ENST00000642315P35222
ENSG00000168036ENST00000642315A0A024R2Q3
ENSG00000168036ENST00000642426P35222
ENSG00000168036ENST00000642426A0A024R2Q3
ENSG00000168036ENST00000642836B4DGU4
ENSG00000168036ENST00000642886A0A2R8Y750
ENSG00000168036ENST00000642986A0A2R8Y5C3
ENSG00000168036ENST00000642992P35222
ENSG00000168036ENST00000642992A0A024R2Q3
ENSG00000168036ENST00000643031P35222
ENSG00000168036ENST00000643031A0A024R2Q3
ENSG00000168036ENST00000643297P35222
ENSG00000168036ENST00000643297A0A024R2Q3
ENSG00000168036ENST00000643541P35222
ENSG00000168036ENST00000643541A0A024R2Q3
ENSG00000168036ENST00000643977P35222
ENSG00000168036ENST00000643977A0A024R2Q3
ENSG00000168036ENST00000643992P35222
ENSG00000168036ENST00000643992A0A024R2Q3
ENSG00000168036ENST00000644138A0A2R8Y804
ENSG00000168036ENST00000644524B4DGU4
ENSG00000168036ENST00000644678B4DGU4
ENSG00000168036ENST00000644867P35222
ENSG00000168036ENST00000644867A0A024R2Q3
ENSG00000168036ENST00000644873A0A2R8Y7Z0
ENSG00000168036ENST00000644906A0A2R8Y815
ENSG00000168036ENST00000645210P35222
ENSG00000168036ENST00000645210A0A024R2Q3
ENSG00000168036ENST00000645276A0A2R8Y5A3
ENSG00000168036ENST00000645320P35222
ENSG00000168036ENST00000645320A0A024R2Q3
ENSG00000168036ENST00000645493B4DGU4
ENSG00000168036ENST00000645900B4DGU4
ENSG00000168036ENST00000645927A0A2R8Y6G0
ENSG00000168036ENST00000645982P35222
ENSG00000168036ENST00000645982A0A024R2Q3
ENSG00000168036ENST00000646074A0A2R8Y543
ENSG00000168036ENST00000646116B4DGU4
ENSG00000168036ENST00000646174B4DGU4
ENSG00000168036ENST00000646369P35222
ENSG00000168036ENST00000646369A0A024R2Q3
ENSG00000168036ENST00000646381B4DGU4
ENSG00000168036ENST00000646725P35222
ENSG00000168036ENST00000646725A0A024R2Q3
ENSG00000168036ENST00000647264A0A2R8Y5Z1
ENSG00000168036ENST00000647390P35222
ENSG00000168036ENST00000647390A0A024R2Q3
ENSG00000168036ENST00000647413A0A2R8YCH5

Expression (GTEx)

0
50
100
150
200
250
300
Adipose - Subcutaneous
Adipose - Visceral
Adrenal Gland
Artery - Aorta
Artery - Tibial
Bladder
Brain - Amygdala
Brain - Anterior cingulate cortex
Brain - Caudate
Brain - Cerebellar Hemisphere
Brain - Cerebellum
Brain - Cortex
Brain - Frontal Cortex
Brain - Hippocampus
Brain - Hypothalamus
Brain - Nucleus accumbens
Brain - Putamen
Brain - Spinal cord
Brain - Substantia nigra
Breast - Mammary Tissue
Cells - Cultured fibroblasts
Cells - EBV - transformed lymphocytes
Cervix - Ectocervix
Cervix - Endocervix
Colon - Sigmoid
Colon - Transverse
Esophagus - Gastroesophageal Junction
Esophagus - Mucosa
Esophagus - Muscularis
Fallopian Tube
Heart - Atrial Appendage
Heart - Left Ventricle
Kidney - Cortex
Kidney - Medulla
Liver
Lung
Minor Salivary Gland
Muscle - Skeletal
Nerve - Tibial
Ovary
Pancreas
Pituitary
Prostate
Skin - Not Sun Exposed
Skin - Sun Exposed
Small Intestine - Terminal Ileum
Spleen
Stomach
Testis
Thyroid
Uterus
Vagina
Whole Blood

Pathways

PathwaySourceExternal ID
Wnt signaling pathwayKEGGko04310
Focal adhesionKEGGko04510
Adherens junctionKEGGko04520
Leukocyte transendothelial migrationKEGGko04670
MelanogenesisKEGGko04916
Pathogenic Escherichia coli infectionKEGGko05130
Colorectal cancerKEGGko05210
Endometrial cancerKEGGko05213
Prostate cancerKEGGko05215
Thyroid cancerKEGGko05216
Basal cell carcinomaKEGGko05217
Wnt signaling pathwayKEGGhsa04310
Focal adhesionKEGGhsa04510
Adherens junctionKEGGhsa04520
Leukocyte transendothelial migrationKEGGhsa04670
MelanogenesisKEGGhsa04916
Pathogenic Escherichia coli infectionKEGGhsa05130
Pathways in cancerKEGGhsa05200
Colorectal cancerKEGGhsa05210
Endometrial cancerKEGGhsa05213
Prostate cancerKEGGhsa05215
Thyroid cancerKEGGhsa05216
Basal cell carcinomaKEGGhsa05217
Arrhythmogenic right ventricular cardiomyopathy (ARVC)KEGGko05412
Arrhythmogenic right ventricular cardiomyopathy (ARVC)KEGGhsa05412
Bacterial invasion of epithelial cellsKEGGko05100
Bacterial invasion of epithelial cellsKEGGhsa05100
HTLV-I infectionKEGGko05166
HTLV-I infectionKEGGhsa05166
Hippo signaling pathwayKEGGhsa04390
Hippo signaling pathwayKEGGko04390
Proteoglycans in cancerKEGGhsa05205
Proteoglycans in cancerKEGGko05205
Rap1 signaling pathwayKEGGhsa04015
Rap1 signaling pathwayKEGGko04015
Thyroid hormone signaling pathwayKEGGhsa04919
Signaling pathways regulating pluripotency of stem cellsKEGGhsa04550
Signaling pathways regulating pluripotency of stem cellsKEGGko04550
Wnt signalingKEGGhsa_M00677
Wnt signalingKEGGM00677
Metabolism of proteinsREACTOMER-HSA-392499
Peptide hormone metabolismREACTOMER-HSA-2980736
Incretin synthesis, secretion, and inactivationREACTOMER-HSA-400508
Synthesis, secretion, and inactivation of Glucagon-like Peptide-1 (GLP-1)REACTOMER-HSA-381771
DiseaseREACTOMER-HSA-1643685
Diseases of signal transductionREACTOMER-HSA-5663202
Signaling by WNT in cancerREACTOMER-HSA-4791275
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
Infectious diseaseREACTOMER-HSA-5663205
Immune SystemREACTOMER-HSA-168256
Innate Immune SystemREACTOMER-HSA-168249
Cytosolic sensors of pathogen-associated DNAREACTOMER-HSA-1834949
LRR FLII-interacting protein 1 (LRRFIP1) activates type I IFN productionREACTOMER-HSA-3134973
Signal TransductionREACTOMER-HSA-162582
Signaling by VEGFREACTOMER-HSA-194138
VEGFA-VEGFR2 PathwayREACTOMER-HSA-4420097
VEGFR2 mediated vascular permeabilityREACTOMER-HSA-5218920
Signaling by Rho GTPasesREACTOMER-HSA-194315
RHO GTPase EffectorsREACTOMER-HSA-195258
RHO GTPases activate IQGAPsREACTOMER-HSA-5626467
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
Formation of the beta-catenin:TCF transactivating complexREACTOMER-HSA-201722
Binding of TCF/LEF:CTNNB1 to target gene promotersREACTOMER-HSA-4411364
Deactivation of the beta-catenin transactivating complexREACTOMER-HSA-3769402
Beta-catenin independent WNT signalingREACTOMER-HSA-3858494
Ca2+ pathwayREACTOMER-HSA-4086398
Cell-Cell communicationREACTOMER-HSA-1500931
Cell junction organizationREACTOMER-HSA-446728
Cell-cell junction organizationREACTOMER-HSA-421270
Adherens junctions interactionsREACTOMER-HSA-418990
Programmed Cell DeathREACTOMER-HSA-5357801
ApoptosisREACTOMER-HSA-109581
Apoptotic execution phaseREACTOMER-HSA-75153
Apoptotic cleavage of cellular proteinsREACTOMER-HSA-111465
Apoptotic cleavage of cell adhesion proteinsREACTOMER-HSA-351906
Developmental BiologyREACTOMER-HSA-1266738
MyogenesisREACTOMER-HSA-525793
CDO in myogenesisREACTOMER-HSA-375170
Breast cancerKEGGko05224
Breast cancerKEGGhsa05224
Listeria monocytogenes entry into host cellsREACTOMER-HSA-8876384
InlA-mediated entry of Listeria monocytogenes into host cellsREACTOMER-HSA-8876493
Fluid shear stress and atherosclerosisKEGGko05418
Fluid shear stress and atherosclerosisKEGGhsa05418

Protein levels (Protein atlas)

Not detected
Low
Medium
High
cerebral cortex
cerebellum
hippocampus
caudate
thyroid gland
parathyroid gland
adrenal gland
nasopharynx
bronchus
lung
oral mucosa
salivary gland
esophagus
stomach 1
stomach 2
duodenum
small intestine
colon
rectum
liver
gallbladder
pancreas
kidney
urinary bladder
testis
epididymis
seminal vesicle
prostate
vagina
ovary
fallopian tube
endometrium 1
endometrium 2
cervix, uterine
placenta
breast
heart muscle
smooth muscle
skeletal muscle
soft tissue 1
soft tissue 2
adipose tissue
skin 1
skin 2
appendix
spleen
lymph node
tonsil
bone marrow

PharmGKB

Entity IDNameTypeEvidenceAssociationPKPDPMIDs
PA162363968lenalidomideChemicalClinicalAnnotationassociatedPD26521987
PA444985Multiple MyelomaDiseaseClinicalAnnotationassociatedPD26521987
PA448871celecoxibChemicalPathwayassociated22336956
PA449165cyclophosphamideChemicalClinicalAnnotationassociatedPD26521987
PA449247dexamethasoneChemicalClinicalAnnotationassociatedPD26521987
PA451644thalidomideChemicalClinicalAnnotationassociatedPD26521987

References

Pubmed IDYearTitleCitations
372789592024MiR-138-5p Inhibits Thyroid Cancer Cell Growth and Stemness by Targeting TRPC5/Wnt/β-Catenin Pathway.0
376493222024Correlation between E-cadherin/β-catenin, Vimentin expression, clinicopathologic features and drug resistance prediction in naïve prostate cancer: A molecular and clinical study.0
378208512024PFKFB3 promotes endometriosis cell proliferation via enhancing the protein stability of β-catenin.0
378702882024Wnt/β-catenin and NFκB signaling synergize to trigger growth factor-free regeneration of adult primary human hepatocytes.1
379530902024Targeted next-generation sequencing of Japanese patients with sinonasal mucosal melanomas identifies frequent NRAS and CTNNB1 mutations.0
379632002024CircMMP2(6,7) Cooperates with β-Catenin and PRMT5 to Disrupt Bone Homeostasis and Promote Breast Cancer Bone Metastasis.1
380436282024METTL3 regulates FAM83D m(6)A modification to accelerate tumorigenesis of triple-negative breast cancer via the Wnt/β-catenin pathway.2
380695652024USP14 promotes the proliferation of cervical cancer via upregulating β-catenin.0
380699062024Metabolic modulation of histone acetylation mediated by HMGCL activates the FOXM1/β-catenin pathway in glioblastoma.0
38184500202427-Hydroxycholesterol activates the GSK-3β/β-catenin signaling pathway resulting in intestinal fibrosis by inducing oxidative stress: effect of dietary interventions.0
382472962024Clinical phenotypic spectrum of CTNNB1 neurodevelopmental disorder.0
382970822024PARP1-stabilised FOXQ1 promotes ovarian cancer progression by activating the LAMB3/WNT/β-catenin signalling pathway.0
383118512024DLK1/DIO3 locus upregulation by a β-catenin-dependent enhancer drives cell proliferation and liver tumorigenesis.1
383245342024β-catenin mediates growth defects induced by centrosome loss in a subset of APC mutant colorectal cancer independently of p53.0
383642522024miR-557 inhibits hepatocellular carcinoma progression through Wnt/β-catenin signaling pathway by targeting RAB10.1

Citation

Brigitte Debuire ; Antoinette Lemoine ; Raphael Saffroy

CTNNB1 (Catenin, beta-1)

Atlas Genet Cytogenet Oncol Haematol. 2002-03-01

Online version: http://atlasgeneticsoncology.org/gene/71/ctnnb1