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FLASH GENE
Symbol CTNNB1 contributors: shn/npt/pgu - updated : 19-10-2020
HGNC name catenin (cadherin-associated protein), beta 1, 88kDa
HGNC id 2514
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
  • YAP1, CTNNB1 and TBX5 form a complex that regulates the expression of genes that promote survival, including BIRC5 and BCL2L1
  • 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
  • RNA-binding protein quaking maintains endothelial barrier function and affects CDH5 and CTNNB1 protein expression
  • 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
  • WNT1 induces GLI1 expression in a SULF2- and CTNNB1-dependent manner
  • 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
  • interplay of WNT1-LEF1 and TGFB1-SMAD3 signaling activates canonical WNT1 target promoters in a manner that depends on CTNNB1 during myoblast proliferation but is independent of CTNNB1 during Skeletal muscle stem cells (MuSCs) quiescence
  • ODF2 restricts CTNNB1 accumulation at the centrosome, thus preventing premature centrosome disjunction
  • ZNF433 enhanced the binding between CTNNB1 and TCF4
  • is the principal coordinator of the CTNNB1 destruction complex, bringing all its major components in close proximity and thereby vastly accelerating CTNNB1 phosphorylation
  • 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