Beta-Catenin

beta-Catenin is a member of the armadillo family of proteins. These proteins have multiple copies of the so-called armadillo repeat domain, which is specialized for protein-protein binding. It 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. beta-Catenin 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, beta-Catenin binds to the product of the APC gene, which is mutated in adenomatous polyposis of the colon. Defects in beta-Catenin can cause colorectal cancer, pilomatrixoma (PTR), medulloblastoma, and ovarian cancer. beta-Catenin is a key dowstream component of the canonical Wnt signaling pathway. In the absence of Wnt, it 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, beta-Catenin 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.

Beta-Catenin Related Areas

Signal Transduction>>Transcription Factor & Regulator>>beta-Catenin/CTNNB1

Stem Cell>>Embryonic Stem Cell (ESC)>>Embryonic Cell Lineage Marker>>beta-Catenin/CTNNB1

Beta-Catenin Related Pathways

• EGFR Signaling Pathway
• Canonical (beta-Catenin-Dependent) Wnt Signaling
• non Canonical (beta-Catenin-Independent) Wnt Signaling

Beta-Catenin Alternative Names

CTNNB1, OK/SW-cl.35, CTNNB, DKFZp686D02253, FLJ25606, FLJ37923 [Homo sapiens]

beta-Catenin, CTNNB1, Bfc, Catnb, Mesc, catenin beta-1 [Mus musculus]

Summaries for Beta-Catenin

Entrez Gene summary for CTNNB1:

The protein encoded by CTNNB1 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 CTNNB1 gene are a cause of colorectal cancer (CRC), pilomatrixoma (PTR), medulloblastoma (MDB), and ovarian cancer. Three transcript variants encoding the same protein have been found for this CTNNB1 gene.

OMIM - description for Beta-Catenin:

Beta-catenin is an adherens junction protein. Adherens junctions (AJs; also called the zonula adherens) are critical for the establishment and maintenance of epithelial layers, such as those lining organ surfaces. AJs mediate adhesion between cells, communicate a signal that neighboring cells are present, and anchor the actin cytoskeleton. In serving these roles, AJs regulate normal cell growth and behavior. At several stages of embryogenesis, wound healing, and tumor cell metastasis, cells form and leave epithelia. This process, which involves the disruption and reestablishment of epithelial cell-cell contacts, may be regulated by the disassembly and assembly of AJs. AJs may also function in the transmission of the 'contact inhibition' signal, which instructs cells to stop dividing once an epithelial sheet is complete.

Wikipedia summary for Beta-Catenin:

Beta-catenin (or β-catenin) is a protein that in humans is encoded by the CTNNB1 gene. In Drosophila, the homologous protein is called armadillo. β-catenin is a subunit of the cadherin protein complex and has been implicated as an integral component in the Wnt signaling pathway.

Human Beta-Catenin Protein General Information

 

• Protein names: Catenin beta-1, Beta-Catenin
• Sequence length: 781 AA.
• Sequence similarities: Belongs to the beta-catenin family. Contains 12 ARM repeats
• Post-translational modification: 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. 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.
• Subunit structure: Two separate complex-associated pools are found in the cytoplasm. The majority is present as component of an E-cadherin/ catenin adhesion complex composed of at least E-cadherin/CDH1 and beta-catenin/beta-Catenin, and possibly alpha-catenin/beta-Catenin; the complex is located to adherens junctions. The stable association of beta-Catenin is controversial as beta-Catenin was shown not to bind to F-actin when assembled in the complex. Alternatively, the beta-Catenin-containing complex may be linked to F-actin by other proteins such as LIMA1. Another cytoplasmic pool is part of a large complex containing 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. Wnt-dependent activation of DVL antagonizes the action of GSK3B. When GSK3B activity is inhibited the complex dissociates, beta-Catenin is dephosphorylated and is no longer targeted for destruction. The stabilized protein translocates to the nucleus, where it binds TCF/LEF-1 family members, TBP, BCL9 and possibly also RUVBL1 and CHD8. Binds CTNNBIP and EP300. CTNNB1 forms a ternary complex with LEF1 and EP300 that is disrupted by CTNNBIP1 binding By similarity. Interacts with TAX1BP3 (via the PDZ domain); this interaction inhibits the transcriptional activity of CTNNB1 By similarity. Interacts with AJAP1, BAIAP1, CARM1, CTNNA3, CXADR and PCDH11Y. Binds SLC9A3R1. Interacts with GLIS2 and MUC1. Interacts with SLC30A9. Interacts with XIRP1 By similarity. Interacts directly with AXIN1; the interaction is regulated by CDK2 phosphorylation of AXIN1 By similarity. Interacts with SCRIB By similarity. Interacts with PTPRU (via the cytoplasmic juxtamembrane domain). Interacts with EMD. Interacts with TNIK and TCF7L2. Interacts with SESTD1 and TRPC4. Interacts with CAV1. Interacts with TRPV4. The TRPV4 and beta-Catenin complex can interact with CDH1. Interacts with VCL By similarity. Interacts with PTPRJ. Interacts with PKT7 and CDK2. Interacts with FAT1 (via the cytoplasmic domain) By similarity. Interacts with NANOS1 and NDRG2. Interacts with isoform 1 of NEK2. Interacts with both isoform 1 and isoform 2 of CDK5. Interacts with PTK6.
• Subcellular location: Cytoplasm. Nucleus. Cytoplasm › cytoskeleton. Cell junction › adherens junction. Cell junction. Cell membrane. Cytoplasm › cytoskeleton › centrosome. Cytoplasm › cytoskeleton › spindle pole. Note: 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. Co-localizes with CDK5 in the cell-cell contacts and plasma membrane of undifferentiated and differentiated neuroblastoma cells.
• Tissue specificity: beta-Catenin is expressed in several hair follicle cell types: basal and peripheral matrix cells, and cells of the outer and inner root sheaths. Expressed in colon. Present in cortical neurons (at protein level).
• Involvement in disease: Defects in beta-Catenin are associated with colorectal cancer (CRC) [MIM:114500]. Note=Activating mutations in CTNNB1 have oncogenic activity resulting in tumor development. Somatic mutations are found in various tumor types, including colon cancers, ovarian and prostate carcinomas, hepatoblastoma (HB), hepatocellular carcinoma (HCC). HBs are malignant embryonal tumors mainly affecting young children in the first three years of life. Defects in beta-Catenin are a cause of pilomatrixoma (PTR) [MIM:132600]; a common benign skin tumor. Defects in beta-Catenin1 are a cause of medulloblastoma (MDB) [MIM:155255]. MDB is a malignant, invasive embryonal tumor of the cerebellum with a preferential manifestation in children.Defects in beta-Catenin are a cause of susceptibility to ovarian cancer (OC) [MIM:167000]. Ovarian cancer common malignancy originating from ovarian tissue. Although many histologic types of ovarian neoplasms 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. Note=A chromosomal aberration involving beta-Catenin is found in salivary gland pleiomorphic adenomas, the most common benign epithelial tumors of the salivary gland. Translocation t(3;8)(p21;q12) with PLAG1. Defects in beta-Catenin may be a cause of mesothelioma malignant (MESOM) [MIM:156240]. 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.

General information above from UniProt

Function for Beta-Catenin Protein

UniProtKB:

Beta-Catenin is a key dowstream 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 Beta-Catenin via BTRC and its subsequent degradation by the proteasome. In the presence of Wnt ligand, Beta-Catenin 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. Beta-Catenin is involved in the regulation of cell adhesion. It acts as a negative regulator of centrosome cohesion. And it is involved in the CDK2/PTPN6/Beta-Catenin/CEACAM1 pathway of insulin internalization. ACLY blocks anoikis of malignant kidney and intestinal epithelial cells and promotes their anchorage-independent growth by downregulating DAPK2.

Genatlas:

• 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
• beta-catenin has dual cellular functions, as a component of both the cadherin-catenin cell adhesion complex and the Wnt signaling pathway
• beta-catenin has 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
• beta-catenin plays a role in signalling of postnatal brain plasticity
• beta-catenin regulates midbrain dopaminergic neurogenesis
• beta-catenin mediates AMH signaling for Müllerian duct regression during male sexual differentiation

Homology for human Beta-Catenin

• ortholog to Ctnnb1, Mus musculus
• ortholog to ctnnb1, Danio renio
• ortholog to Ctnnb1, Rattus norvegicus
• ortholog to CTNNB1, Pan troglodytes

Phenotype Information for Beta-Catenin

• Gene/Locus: CTNNB1
• Phenotype: Colorectal cancer
  Hepatoblastoma
  Hepatocellular carcinoma
  Ovarian cancer
  Pilomatricoma
  

Phenotype Information for Beta-Catenin from OMIM (Online Mendelian Inheritance in Man)