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FLASH GENE
Symbol CTNNB1 contributors: shn/npt/pgu - updated : 19-10-2016
HGNC name catenin (cadherin-associated protein), beta 1, 88kDa
HGNC id 2514
Corresponding disease
EVR7 familial exudative vitreoretinopathy 7
MRD19 mental retardation, autosomal dominant 19
Location 3p22.1      Physical location : 41.240.941 - 41.281.939
Synonym name beta-catenin
Synonym symbol(s) CTNNB, DKFZp686D02253, FLJ25606, FLJ37923, MRD19, armadillo
DNA
TYPE functioning gene
STRUCTURE 41.00 kb     16 Exon(s)
10 Kb 5' upstream gene genomic sequence study
regulatory sequence cytosine-phosphate-guanine/HTF
Binding site   hormone
text structure
  • a major site for transcription initiation was identified as an A residue 214 nucleotides upstream of the ATG initiation codon
  • potential binding sites for several transcription factors, such as NF kappa B, SP1, AP2, and EGR1
    • MAPPING cloned Y linked N status provisional
    Map pter - D3S3522 - D3S3658 - CTNNB1 - D3S2407- D3S3563 - cen By FISH and analysis of somatic cell hybrids the CTNNB1 gene has been mapped to 3p21
    Physical map
    MYRIP 3p21.3 myosin VIIA and Rab interacting protein GC20 3p21.33 translation factor sui1 homolog ENTPD3 3p21.3 ectonucleoside triphosphate diphosphohydrolase 3 RPL14 3p23-p21.2 ribosomal protein L14 FLJ90764 3p21.33 hypothetical protein FLJ90764 MGC50836 3p21.33 hypothetical protein MGC50836 FLJ45246 3p21.33 FLJ45246 protein LOC344682 3p21.33 similar to Elongation factor 1-gamma (EF-1-gamma) (eEF-1B gamma) LOC389112 3 similar to ribosomal protein S27 MRPS31P1 3p21.33 mitochondrial ribosomal protein S31 pseudogene 1 CTNNB1 3p22-p21.3 catenin (cadherin-associated protein), beta 1, 88kDa DKFZp434E1822 3p21.33 hypothetical protein DKFZp434E1822 FLJ20574 3p21.33 hypothetical protein FLJ20574 LOC391529 3 similar to SMN interacting protein1-beta OIP106 3p25.3-p24.1 similar to SMN interacting protein1-beta CCK 3p22.1-p21.3 cholecystokinin LOC391530 3 similar to SALL4B MGC26768 3p21.33 hypothetical protein MGC26768 VIPR1 3p22 vasoactive intestinal peptide receptor 1 SEC22L3 3p24.3-p22.1 SEC22 vesicle trafficking protein-like 3 (S. cerevisiae) SS18L2 3p21 synovial sarcoma translocation gene on chromosome 18-like 2 NKTR 3p23-p21 natural killer-tumor recognition sequence KIAA1190 3p21.33 hypothetical protein KIAA1190 KBTBD5 3p21.33 kelch repeat and BTB (POZ) domain containing 5 KIAA1173 3p21.33 KIAA1173 protein FLJ25467 3p21.33 hypothetical protein FLJ25467 HIG1 3p21.33 likely ortholog of mouse hypoxia induced gene 1 CCBP2 3p21.32-p21.31 chemokine binding protein 2
    RNA
    TRANSCRIPTS type messenger
    text Variants 1, 2, 3 encode the same protein
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    15 splicing 3720 88 781 - 1995 7702605
    16 splicing 3256 88 781 - 1995 7702605
    16 splicing 3415 88 781 - 1995 7702605
    EXPRESSION
    Rna function mRNAs were abundant in both dorsolateral prefrontal cortex and hippocampus, with a distinct neuronal localization, and also abundant in the granule cells of the dentate gyrus and pyramidal cells of Ammon horn
    Type ubiquitous
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Digestivemouth   predominantly
    Lymphoid/Immunethymus   highly
    Nervousbrainforebraincerebral cortexfrontal cortexpredominantly Homo sapiens
     brainlimbic systemhippocampus predominantly Homo sapiens
     brainmidbrainhypothalamus predominantly
     braindiencephalonamygdala highly
     brainbasal nucleistriatum predominantly
    Respiratoryrespiratory tracttrachea  predominantly
    Urinarybladder   highly
    Visualeyeretina   
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • N-terminal domain (NTD), containing the binding site for alpha-catenin and the phosphorylation sites for GSK3 and CK1
  • a central region containing 12 armadillo (ARM) repeats (AAs 138–664), crucial for its roles in cell adhesion and signaling
  • a C-terminal domain (CTD), and at the start of the CTD is an alpha-helix motif (AAs 667–683), termed Helix-C, that facilitates the binding of proteins to the ARM repeats and is essential for CTNNB signaling
    • HOMOLOGY
    interspecies ortholog to Ctnnb1, Mus musculus
    ortholog to ctnnb1, Danio renio
    ortholog to Ctnnb1, Rattus norvegicus
    ortholog to CTNNB1, Pan troglodytes
    Homologene
    FAMILY
  • beta-catenin family
    • CATEGORY regulatory , signaling
    SUBCELLULAR LOCALIZATION     plasma membrane,junction,adherens
        intracellular
    intracellular,cytoplasm,cytosolic
    intracellular,cytoplasm,cytoskeleton,microtubule,centrosome
    basic FUNCTION
  • beta-catenin protein is implicated in signal transduction and associates with both the cell adhesion protein E-cadherin and the tumor suppressor gene product APC
  • have dual cellular functions, as a component of both the cadherin-catenin cell adhesion complex and the Wnt signaling pathway
  • having functions in signal transduction in the Wnt signalling pathway, which is implicated in hair follicle (HF) morphogenesis
  • the beta-catenin and TCF control the expression of the EphB2/EphB3 receptors and their ligand, ephrin B1 in colorectal cancer and along the crypt-villus axis
  • beta-catenin can function in the decision of precursors to proliferate or differentiate during mammalian neuronal development and can regulate cerebral cortical size by controlling the generation of neuronal precursor cells
  • In rat, the beta-catenin is a mediator of dendritic development
  • In mouse, beta-catenin activity in neural crest cells promoted the formation of sensory neural cells in vivo at the expense of virtually all other neural crest derivatives
  • beta-catenin has a role in establishing bipolar mitotic spindles
  • the cadherin-beta catenin complex is involved in synapse development and modulation of synaptic connectivity and activity
  • having a functional role during proliferation of islet-derived precursor cells and activated beta-catenin signalling may also be important during islet-derived precursor cells derivation from islets
  • beta-catenin may has a general role in the synaptic remodeling and stabilization underlying long-term memory in adult mice
  • role in signalling of postnatal brain plasticity
  • regulates midbrain dopaminergic neurogenesis
  • mediates AMH signaling for Müllerian duct regression during male sexual differentiation
  • important role of a novel signalling pathway mediated by PRKCA-HDAC6-CTNNB1 in controlling IRF3-mediated transcription
  • its signaling in sertoli cells downregulates spermatogonial stem cell activity via WNT4
  • CTNND1, CTNNB1 have distinct but complementary roles in strengthening cadherin-mediated adhesion
  • is critical for cerebellar foliation and lamination
  • is required for the differentiation of thymic epithelial cells (TECs), thereby contributing to thymocyte development in the postnatal thymus
  • regulated CTNNB1 in mesenchyme is important for epithelial cell differentiation during female reproductive tract development
  • plays a role in cell division and differentiation in the cochlear sensory epithelium
  • plays an essential role in lung tumorigenesis
  • is a critical regulator in the development of behavioural resilience, activating a network that includes DICER1 and downstream microRNAs
  • switching modes of CTNNB1 function are associated with consecutive cell fate specification and stage-specific progenitor proliferation
  • activation of YAP1 and CTNNB1 may represent a master regulator of mechanical strain-induced cell proliferation
  • role of CTNNB1 signaling in the development of the retinal vasculature
    • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    key component of Wnt signalling
    a component
  • ARHGEF7 forms a complex with cadherin, CTNNB1, and SCRIB at synapses and enhances localized actin polymerization in rat hippocampal neurons
    • INTERACTION
    DNA
  • beta-catenin activates transcription from the cyclin D1 promoter
  • The beta-catenin induces expression of PKD1 gene
  • The beta-catenin-TCF4 complex binds the enhancer region of the GLCE promoter
    • RNA
    small molecule
    protein
  • interacting with ERBB2 (ERBB2-induced signaling is also directly liked to the cadherin-mediated cell adhesion and "invasion-suppressor" system through CTNNB1 and plakoglobin in cancers)
  • RUVBL2 interaction partner (binds beta-catenin in the region of Armadillo repeats 2-5 and, more importantly, also binds the TATA box binding protein, and involved in the nuclear function of beta-catenin)
  • beta-catenin forms a 1:1 heterodimer with alpha-catenin
  • in normal retina tissues and in retinoblstoma, beta-catenin is associated with N-cadherin
  • 14-3-3-zeta protein
  • beta-catenin interacts with FOXO transcription factors
  • beta-catenin is required for osteoblast lineage differentiation
  • interacting with DKK3 (is a negative regulator of beta-catenin and its downregulation contribute to an activation of the beta-catenin signaling pathway)
  • ZEB1 is an effector of CTNNB1/TCF4 signaling in epithelial-to-mesenchymal transition and tumor progression
  • stimulates KCNA5 and thus participates in the shaping of the cardiac action potential and further KCNA5 sensitive cellular functions
  • CTNNB1 enhanced the KCNE1/KCNQ1 protein abundance in the cell membrane
  • SIRT1 inhibits proliferation of ZG16B, a novel oncogene, by suppression of CTNNB1
  • PTPN11 forms an enzyme–substrate complex with CTNNB1
  • CTNNB1 activates the HOXA10 and CDX4 genes in myeloid progenitor cells
  • ARRB1 is a nuclear transcriptional regulator of EDN1-induced CTNNB1 signaling
  • expression of BRMS1L depends on CTNNB1 activity and contributes to FSHB induction by GNRH1
  • CDH5 interacts with CTNND1and CTNNB1 through its cytoplasmic tail
  • WNT/RSPO1/CTNNB1 signals control axonal sorting and lineage progression in Schwann cell development
  • SKP2 may regulate CTNNB1 and its target gene expression to orchestrate hematopoietic stem cell (HSC) homing
  • MMP7 catalytic activity regulates CTNNB1 localization and signaling activation in lung epithelial cells
  • TDG, as a new coactivator, promotes CTNNB1/TCFs transactivation and functionally cooperates with CREBBP in canonical WNT signaling
  • SIRT2, inhibits the Wnt signaling pathway in nonmalignant cells by binding to CTNNB1
  • a COPS5/CTNNB1/SIAH1 interaction network that might control CTNNB1 degradation in colorectal cancer cells
  • complex role for HSF1 in the regulation of ELAVL1 and CTNNB1 expression that may be significant in mammary carcinogenesis
  • TRAF4 mediated the translocation of CTNNB1 from the cytoplasm to the nucleus, thereby facilitating activation of the Wnt signaling pathway in breast cancer
  • PROM1 associates with membrane CTNNB1 in early placodes, and its continued expression correlates with loss of CTNNB1 and CDH1 from the cell membrane at a time when CDH1 transcriptional repressors SNAI1 and SNAI2 are not implicated
  • CTNNB1 links VHL to AURKA and loss of primary cilia in renal cell carcinoma
  • HDAC7 suppresses RUNX2 activity and osteoblast differentiation, and suppresses proliferation and CTNNB1 activity in chondrocytes
  • BEX2 affects the invasion and migration ability of glioma cells by regulating CTNNB1
  • HSPH1 is required for WNT signaling, since depletion of HSPH1 compromises CTNNB1 accumulation and target gene transcription upon WNT stimulation
  • molecular mechanism by which glucose deprivation can induce the GSK3B-independent protein degradation of CTNNB1, leading to autophagy
  • TCF7L2 is a transcriptional co-activator of CTNNB1
  • MACF1 promotes osteoblast differentiation by promoting CTNNB1/HNF1A/RUNX2 signaling axis
  • presynaptic CTNNB1 expression enhanced release probability of glutamatergic synapses, and newly identified CTNNB1-interacting protein SRCIN1 is required in the presynaptic locus for mediating these effects
  • MACF1 was found to enhance CTNNB1 expression and activity, and mechanical unloading decreased CTNNB1 expression through MACF1
    • cell & other
    REGULATION
    repressed by APC gene
    the transcription factor E2F1
    ASSOCIATED DISORDERS
    corresponding disease(s) MRD19 , EVR7
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral germinal mutation      
    missense mutations in exon-3 associated to histologically, a more aggressive hepatocellular carcinoma (also, mutations might lead to HCC in the absence of cirrhosis)
    tumoral germinal mutation      
    highly common in desmoid tumors (patients harboring CTNNB1 (45F) mutations are at particular risk for recurrence)
    tumoral somatic mutation      
    in ovarian malignant transformation with a characteristic phenotype: endometrioid ovarian carcinoma
    tumoral somatic mutation      
    in HNPCC tumors existed within the regulatory domain of beta-catenin
    tumoral     --over  
    beta-catenin accumulation may play a role in the development of hepatoblastoma and activating mutations may substitute biallelic APC inactivation in this tumor type
    tumoral germinal mutation      
    in pilomatricomas
    constitutional       loss of function
    of YAP1- and CTNNB1-mediated transcription blocked cell cycle reentry and progression through G1 into S phase, respectively
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    SystemTypeDisorderPubmed
    cancerreproductiveprostate
    CTNNB1 inhibition is a potential therapeutic option for a subset of patients with basal-derived prostate cancer (CaP)
    cancerendocrinepancreas
    CTNNB1- signalling is an effective therapeutic target for MEN1-mutant
    cancerlung 
    targeting the β-catenin pathway may provide novel strategies to prevent lung cancer development or overcome resistance to EGFR tyrosine kinase inhibitors (TKI)
    ANIMAL & CELL MODELS
  • deletion of exon 3 in beta -catenine mice leads to adenomatous intestinal polyps resembling those in Apc knockout mice
  • Transgenic mice that overproduced an oncogenic form of beta-catenin in the epithelial cells of the kidney developed severe polycystic lesions
  • inactivation of mouse beta-catenin leads to ectopic formation of chondrocytes at the expense of osteoblast differentiation during both intramembranous and endochondral ossification
  • conditional inactivation of mouse beta-catenin blocks the differentiation and the development of osteoblast precursors into chondrocytes
  • conditional deletion of beta-catenin in mouse proepicardium led to impaired formation of coronary arteries. Mutant mice exhibited impaired epicardial development, including failed expansion of the subepicardial space, blunted invasion of the myocardium, and impaired differentiation of epicardium-derived mesenchymal cells into coronary smooth muscle cells
  • mice carrying CTNNB1 loss-of-function mutations show a delay in axonal sorting