CTNNB1
The protein encoded by this gene is part of a complex of proteins that constitute adherens junctions (AJs). AJs are necessary for the creation and maintenance of epithelial cell layers by regulating cell growth and adhesion between cells. The encoded protein also anchors the actin cytoskeleton and may be responsible for transmitting the contact inhibition signal that causes cells to stop dividing once the epithelial sheet is complete. Finally, this protein binds to the product of the APC gene, which is mutated in adenomatous polyposis of the colon. Mutations in this gene are a cause of colorectal cancer (CRC), pilomatrixoma (PTR), medulloblastoma (MDB), and ovarian cancer. Alternative splicing results in multiple transcript variants.
Alternative Names
Catenin Beta 1; Catenin (Cadherin-Associated Protein), Beta 1, 88kDa; CTNNB; Catenin (Cadherin-Associated Protein), Beta 1 (88kD); Catenin (Cadherin-Associated Protein), Beta 1; Catenin Beta-1;
Function
Key downstream component of the canonical Wnt signaling pathway. In the absence of Wnt, forms a complex with AXIN1, AXIN2, APC, CSNK1A1 and GSK3B that promotes phosphorylation on N-terminal Ser and Thr residues and ubiquitination of CTNNB1 via BTRC and its subsequent degradation by the proteasome. In the presence of Wnt ligand, CTNNB1 is not ubiquitinated and accumulates in the nucleus, where it acts as a coactivator for transcription factors of the TCF/LEF family, leading to activate Wnt responsive genes. Involved in the regulation of cell adhesion, as component of an E-cadherin:catenin adhesion complex (By similarity). Acts as a negative regulator of centrosome cohesion. Involved in the CDK2/PTPN6/CTNNB1/CEACAM1 pathway of insulin internalization. Blocks anoikis of malignant kidney and intestinal epithelial cells and promotes their anchorage-independent growth by down-regulating DAPK2. Disrupts PML function and PML-NB formation by inhibiting RANBP2-mediated sumoylation of PML. Promotes neurogenesis by maintaining sympathetic neuroblasts within the cell cycle (By similarity). Involved in chondrocyte differentiation via interaction with SOX9: SOX9-binding competes with the binding sites of TCF/LEF within CTNNB1, thereby inhibiting the Wnt signaling (By similarity).
Biological Process
Adherens junction assembly
Beta-catenin destruction complex disassembly
Beta-catenin-TCF complex assembly
Branching involved in blood vessel morphogenesis
Canonical Wnt signaling pathway
Canonical Wnt signaling pathway involved in midbrain dopaminergic neuron differentiation
Canonical Wnt signaling pathway involved in negative regulation of apoptotic process
Canonical Wnt signaling pathway involved in positive regulation of cardiac outflow tract cell proliferation
Canonical Wnt signaling pathway involved in positive regulation of epithelial to mesenchymal transition
Cell adhesion
Cell-cell adhesion
Cellular response to growth factor stimulus
Cellular response to indole-3-methanol
Detection of muscle stretch
Embryonic skeletal limb joint morphogenesis
Endothelial tube morphogenesis
Entry of bacterium into host cell
Epithelial to mesenchymal transition
Hair cell differentiation
Midbrain dopaminergic neuron differentiation
Negative regulation of angiogenesis
Negative regulation of apoptotic process
Negative regulation of cell population proliferation
Negative regulation of mitotic cell cycle, embryonic
Negative regulation of protein sumoylation
Negative regulation of transcription, DNA-templated
Neuron projection extension
Positive regulation of apoptotic process
Positive regulation of DNA-binding transcription factor activity
Positive regulation of epithelial to mesenchymal transition
Positive regulation of heparan sulfate proteoglycan biosynthetic process
Positive regulation of histone H3-K4 methylation
Positive regulation of muscle cell differentiation
Positive regulation of neuroblast proliferation
Positive regulation of neuron apoptotic process
Positive regulation of telomerase activity
Positive regulation of telomere maintenance via telomerase
Positive regulation of transcription, DNA-templated
Positive regulation of transcription by RNA polymerase II
Positive regulation of type I interferon production
Proteasome-mediated ubiquitin-dependent protein catabolic process
Protein localization to cell surface
Protein polyubiquitination
Regulation of angiogenesis
Regulation of calcium ion import
Regulation of canonical Wnt signaling pathway
Regulation of centriole-centriole cohesion
Regulation of centromeric sister chromatid cohesion
Regulation of fibroblast proliferation
Regulation of nephron tubule epithelial cell differentiation
Regulation of neurogenesis
Regulation of protein localization to cell surface
Regulation of smooth muscle cell proliferation
Regulation of transcription initiation from RNA polymerase II promoter
Response to drug
Response to estradiol
Stem cell population maintenance
Sympathetic ganglion development
Viral process
Wnt signaling pathway
Wnt signaling pathway, calcium modulating pathway
Cellular Location
Nucleus; Cytoskeleton; Centrosome; Spindle pole; Cilium basal body; Cell membrane; Cytoplasm; Adherens junction; Cell junction; Synapse. Colocalized with RAPGEF2 and TJP1 at cell-cell contacts (By similarity). Cytoplasmic when it is unstabilized (high level of phosphorylation) or bound to CDH1. Translocates to the nucleus when it is stabilized (low level of phosphorylation). Interaction with GLIS2 and MUC1 promotes nuclear translocation. Interaction with EMD inhibits nuclear localization. The majority of beta-catenin is localized to the cell membrane. In interphase, colocalizes with CROCC between CEP250 puncta at the proximal end of centrioles, and this localization is dependent on CROCC and CEP250. In mitosis, when NEK2 activity increases, it localizes to centrosomes at spindle poles independent of CROCC. Colocalizes with CDK5 in the cell-cell contacts and plasma membrane of undifferentiated and differentiated neuroblastoma cells. Interaction with FAM53B promotes translocation to the nucleus.
Involvement in disease
Colorectal cancer (CRC): A complex disease characterized by malignant lesions arising from the inner wall of the large intestine (the colon) and the rectum. Genetic alterations are often associated with progression from premalignant lesion (adenoma) to invasive adenocarcinoma. Risk factors for cancer of the colon and rectum include colon polyps, long-standing ulcerative colitis, and genetic family history.
Pilomatrixoma (PTR): Common benign skin tumor.
Ovarian cancer (OC): The term ovarian cancer defines malignancies originating from ovarian tissue. Although many histologic types of ovarian tumors have been described, epithelial ovarian carcinoma is the most common form. Ovarian cancers are often asymptomatic and the recognized signs and symptoms, even of late-stage disease, are vague. Consequently, most patients are diagnosed with advanced disease.
Mesothelioma, malignant (MESOM): An aggressive neoplasm of the serosal lining of the chest. It appears as broad sheets of cells, with some regions containing spindle-shaped, sarcoma-like cells and other regions showing adenomatous patterns. Pleural mesotheliomas have been linked to exposure to asbestos.
Neurodevelopmental disorder with spastic diplegia and visual defects (NEDSDV): An autosomal dominant disorder characterized by global developmental delay, severe intellectual disability with absent or very limited speech, microcephaly, spasticity, and visual abnormalities.
Vitreoretinopathy, exudative 7 (EVR7): A form of exudative vitreoretinopathy, a disorder of the retinal vasculature characterized by an abrupt cessation of growth of peripheral capillaries, leading to an avascular peripheral retina. This may lead to compensatory retinal neovascularization, which is thought to be induced by hypoxia from the initial avascular insult. New vessels are prone to leakage and rupture causing exudates and bleeding, followed by scarring, retinal detachment and blindness. Clinical features can be highly variable, even within the same family. Patients with mild forms of the disease are asymptomatic, and their only disease related abnormality is an arc of avascular retina in the extreme temporal periphery.
PTM
Phosphorylation at Ser-552 by AMPK promotes stabilizion of the protein, enhancing TCF/LEF-mediated transcription (By similarity). Phosphorylation by GSK3B requires prior phosphorylation of Ser-45 by another kinase. Phosphorylation proceeds then from Thr-41 to Ser-37 and Ser-33. Phosphorylated by NEK2. EGF stimulates tyrosine phosphorylation. Phosphorylation on Tyr-654 decreases CDH1 binding and enhances TBP binding. Phosphorylated on Ser-33 and Ser-37 by HIPK2 and GSK3B, this phosphorylation triggers proteasomal degradation. Phosphorylation on Ser-191 and Ser-246 by CDK5. Phosphorylation by CDK2 regulates insulin internalization. Phosphorylation by PTK6 at Tyr-64, Tyr-142, Tyr-331 and/or Tyr-333 with the predominant site at Tyr-64 is not essential for inhibition of transcriptional activity.
Ubiquitinated by the SCF(BTRC) E3 ligase complex when phosphorylated by GSK3B, leading to its degradation. Ubiquitinated by a E3 ubiquitin ligase complex containing UBE2D1, SIAH1, CACYBP/SIP, SKP1, APC and TBL1X, leading to its subsequent proteasomal degradation.Ubiquitinated and degraded following interaction with SOX9 (By similarity).
S-nitrosylation at Cys-619 within adherens junctions promotes VEGF-induced, NO-dependent endothelial cell permeability by disrupting interaction with E-cadherin, thus mediating disassembly adherens junctions.
O-glycosylation at Ser-23 decreases nuclear localization and transcriptional activity, and increases localization to the plasma membrane and interaction with E-cadherin CDH1.
Deacetylated at Lys-49 by SIRT1.
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