Cancer Protein Description
This report provides a detailed description of a selected cancer protein with information collected from various sources, including UniProt, the Wellcome Trust Sanger Institute’s Catalogue of Somatic Mutations in Cancer (COSMIC), and the Atlas of Genetics and Cytogenetics in Oncology and Haematology.
| Protein Name: | CTNNB1 |
| Gene Name: | CTNNB1 |
| Protein Full Name: | Catenin beta-1 |
| Alias: | Beta-catenin; Catenin, beta; CATNB; CTNB1; CTNNB |
| Mass (Da): | 85497 |
| Number AA: | 781 |
| UniProt ID: | P35222 |
| Locus ID: | 1499 |
| COSMIC ID: | CTNNB1 |
| Gene location on chromosome: | 3p22-p21.3 |
| Number of cancer specimens: | 54706 |
| Percent of cancer specimens with mutations: | 9.55 |
| General distribution of mutations: | Narrow |
| Location of most mutations: | Narrow distribution (AA 1-47) of mutation sites with point mutations, complex mutations, deletions and some insertions mostly at the N-terminus. |
| Commonly recorded point mutations: | T41A (1038); S45F (650); S45P (237); S37F (211); S33C (170); S37C (163); D32Y (145); T41I (121); D32N (110); |
| Normal role description: | Anchors acting cytoskeleton, part of a complex of proteins that constitute adherens junctions. Key dowstream component of the canonical Wnt signalling 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. 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 downregulating DAPK2. 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. |
| Commentary on involvement of protein in cancer: | The N-terminus of CTNNB1 can be heavily phosphorylated, and this might result in its unstabilization and release in cytoplasm. T41A in hepatoblastoma and hepatocellular carcinoma; also in a desmoid tumor; strongly reduces phosphorylation and degradation; abolishes phosphorylation on Ser-33 and Ser-37 and enhances transactivation of target genes. |