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: | Ret |
| Gene Name: | RET |
| Protein Full Name: | Proto-oncogene tyrosine-protein kinase receptor Re |
| Alias: | C-ret; EC 2.7.10.1; GDNF receptor; Glial cell line-derived neurotropic factor receptor |
| Mass (Da): | 124319 |
| Number AA: | 1114 |
| UniProt ID: | P07949; B4DGX8; O43519; Q8IZR8; Q8NFE8; Q99886; Q9UM90; Q9UMQ4; F5CNE9; Q14277; Q15300; Q9UE13 |
| Locus ID: | 5979 |
| COSMIC ID: | RET |
| Gene location on chromosome: | 10q11.2 |
| Cancer protein type: | OP |
| Effect of cancer mutation on protein: | GAIN |
| Effect of active protein on cancer: | PROMOTES |
| Number of cancer specimens: | 29162 |
| Percent of cancer specimens with mutations: | 3.61 |
| General distribution of mutations: | Narrow |
| Location of most mutations: | Two main regions, one small cluster (AA 591-634) and a slightly larger cluster (AA 918) with point mutations, and neighbouring deletions (AA 592-632 and-898). |
| Commonly recorded point mutations: | M918T (494); |
| Mutations observed as inherited: | Multiple endocrine neoplasia type 2. Hirschprung's disease |
| Deregulated in translocations: | Papillary thyroid carcinomas. Fusion partners include H4, R1a, ELE1, Htif1, Htifg, KTN1, RFG9, ELKS and PCM1. |
| Normal role description: | RET is a receptor-tyrosine kinase that is activated upon binding glial-derived neurotrophic factor (GDNF). Normally involved in the differentiation of neural crest cells and organs (salivary glands, spleen, thyroid, thymus etc). Given its vary clearly identified role in thyroid carcinoma and also the known oncogenic potential of RTKs, it is not surprising that this gene is characterized as a proto-oncogene. Fusion partners result in disregulated kinase activity related both to constituent activation and promiscuous protein interaction. |
| Commentary on involvement of protein in cancer: | M918T in RADYS, MEN2B and MTC; sporadic form; somatic mutation. M918 is located in the kinase catalytic domain in the activation loop just before subdomain VIII. |