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Structure
When β-catenin was sequenced, it was found to be a member of the armadillo family of proteins. These proteins have multiple copies of the so-called armadillo repeat domain, which is comprised of three helices. The first armadillo (arm) repeat, near the N-terminal, is different from all the others in that it has an elongated helix with a kink, formed by the fusion of helices 1 and 2.

Structural element HelixC caps the C-terminus end of the arm repeats, shielding hydrophobic residues. It has been shown that HelixC is not necessary for β-catenin to function in cell-cell adhesion, but rather is important in the Wnt signaling pathway. HelixC is speculated to be involved in the recruitment and binding of β-catenin coactivators. Collectively, the unique N and C-terminal tails are hypothesized to increase specificity in protein-protein interactions, since they flank the less specific, more conserved arm repeats.

Clinical significance
The gene that codes for β-catenin can function as an oncogene. Increased nuclear β-catenin levels has been noted in basal cell carcinoma (BCC), head and neck squamous cell carcinoma (HNSCC), prostate cancer (CaP), colorectal cancer (CRC), pilomatrixoma (PTR), medulloblastoma (MDB), and ovarian cancer. In the nucleus, β-catenin interacts with TCF/LEF family transcription factors which go on to activate various oncogenes associated with growth and proliferation. β-catenin inhibitors can aid in the treatment of these cancers. Overexpression of β-catenin can be caused by mutation of the β-catenin gene itself, by excessive Wnt signalling, or by the dissociation of the APC-axin-GSK-3 complex.

Tumor proliferation in basal cell carcinoma has been correlated with increased nuclear β-catenin levels. The cause of this increase is speculated to be overexpression of Wnt ligands due to the lack of evidence for a β-catenin gene mutation.

Overexpression of β-catenin in colorectal cancer has been attributed to an APC gene mutation. Adenomas were found to have higher than normal levels of cytoplasmic β-catenin yet lacked overexpressed nuclear β-catenin, while intramucosal cancers did have overexpressed nuclear β-catenin. This suggests that nuclear translocation of β-catenin affects adenoma-carcinoma progression. The aid provided by nuclear translocation to the development of intramucosal cancer is independent of APC gene mutation.

Pilomatricoma is a benign skin tumor that is associated with the hair matrix. β-catenin expression has been correlated with terminal hair shaft differentiation. After the differentiation is completed, β-catenin expression ceases. However in Pilomatricoma, expression of β-catenin in high levels is present at all times, not only during the differentiation process. The exact cause of this overexpression is undetermined, speculated to be either a mutation in the APC gene or the β-catenin gene.

Medulloblastoma is a pediatric brain tumor, sometimes associated with a β-catenin gene mutation. Medulloblastoma's with high levels of nuclear β-catenin, resulting from a β-catenin gene mutation, are shown to have a more favorable outcome than medulloblastoma's without nuclear β-catenin accumulation.

The overexpression of β-catenin in prostate cancer is thought to be caused by excessive Wnt signalling. The overexpressed β-catenin can associate with TCF/LEF transcription factors to activate specific genes or can bind to the androgen receptor, which regulates prostate growth.

The transduction of 'stable' β-catenin, containing alanine in place of the four serine or threonine residues so therefore are not affected by the GSK-3 degradation pathway, have been found to increase survival rates of regulatory T cells and induce anergy in naive CD25- nonregulatory T cells, making stable β-catenin a candidate for further studies on its application with transplanted regulatory T cells to combat inflammatory and autoimmune diseases.