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: | NOTCH1 |
| Gene Name: | NOTCH1 |
| Protein Full Name: | Neurogenic locus notch homolog protein 1 |
| Alias: | neurogenic locus notch 1; NOTC1; notch 1 (translocation-associated); Notch 1, translocation-associated; Notch homolog 1, translocation-associated (Drosophila) (TAN1); Notch1; TAN1; translocation-associated notch protein TAN-1 |
| Mass (Da): | 272505 |
| Number AA: | 2555 |
| UniProt ID: | P46531 |
| Locus ID: | 4851 |
| COSMIC ID: | NOTCH1 |
| Gene location on chromosome: | 9q34.3 |
| Cancer protein type: | OP/TSP |
| Effect of cancer mutation on protein: | BOTH |
| Effect of active protein on cancer: | MIXED |
| Number of cancer specimens: | 30566 |
| Percent of cancer specimens with mutations: | 6.22 |
| General distribution of mutations: | Multi-site |
| Location of most mutations: | Two main clusters of mutations: AA 1555-1784 and AA 2272-2529 with point mutations, complex mutations, insertions and deletions. The first cluster is richer in point mutations, whereas the second cluster has more complex mutations. |
| Commonly recorded point mutations: | P2514fs* (251); L1600P (67); |
| Deregulated in translocations: | t(7;9) (q34;q34.3): Notch1-TCRB; Acute T-cell leukemias |
| Normal role description: | TAN1 is a membrane-bound receptor for Jagged1, Jagged2 and Delta1 ligands. Ligand binding will lead to cleavage of a the extracellular domain of TAN1 leading to release of the extracellular domain-ligand complex and the intracellular domain (NICD). The NICD will form a transcriptional activator complex with CBF1 which will translocate to the nucleus to activate transcription of target genes. TAN1 signalling has important biological functions in neuronal development and function, angiogenesis, cell fate decisions during development and lymphocyte function. It is involved in the maturation of both CD4+ and CD8+ cells in the thymus. Aberrant activity is associated with various human cancers, in particular with T cell malignancies. Aberrant functioning of TAN1 has been implicated in various cancers. Inactivity of TAN1 signalling is implicated in thyroid, gastrointestinal and small-cell lung cancer (SCLC). While increased expression and activation of TAN1 has been associated with leukemias, lymphomas, breast cancer and skin cancer. The function of TAN1 in cancer development is tissue specific and may function as both an oncogene or tumour suppressor protein. |