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: | FGFR3 |
| Gene Name: | FGFR3 |
| Protein Full Name: | Fibroblast growth factor receptor 3 |
| Alias: | ACH; CD333; CEK2; EC 2.7.10.1; FGFR-3; Fibroblast growth factor receptor 3; Heparin-binding growth factor receptor; JTK4; Kinase FGFR3; MFR3; SAM3 |
| Mass (Da): | 87710 |
| Number AA: | 806 |
| UniProt ID: | P22607 |
| Locus ID: | 2261 |
| COSMIC ID: | FGFR3 |
| Gene location on chromosome: | 4p16.3 |
| Cancer protein type: | OP |
| Effect of cancer mutation on protein: | GAIN |
| Effect of active protein on cancer: | PROMOTES |
| Number of cancer specimens: | 35566 |
| Percent of cancer specimens with mutations: | 9.64 |
| General distribution of mutations: | Narrow |
| Location of most mutations: | Two main clusters at AA 248-249 and AA 370-390 with point mutations. A couple of insertions and a deletion also occur in the first cluster. |
| Commonly recorded point mutations: | S249C (1822); Y373C (574); R248C (398); G370C (158); S371C (55); G697C (44): K650E (79); K650M (82). AA 650 and 697 are in the kinase catalytic domain. |
| Deregulated in translocations: | Multiple myelomas. Fusion partners include IgH and Tel. No fusion protein is translated, promoter exchange with IgH leads to increased oncogenesis. |
| Normal role description: | FGFR3 is a receptor-tyrosine kinase that is activated upon binding fibroblast growth factor (FGF). Extracellular ligand binding induces homo- or hetero- dimerization of FGFR to activate signalling. FGFRs have an essential role in regulating cellular differentiation, proliferation and apoptosis. The FGFR3 isoform is specifically involved in chondrocyte development which is physiologically linked to normal skeleton development. Defects in FGFR3 can lead to dwarfism. Overexpressed FGFR3 can promote activation of SHP2 and STAT signalling pathways.Mutations which promote constitutive dimerization of FGFR and kinase activation or impairs internalization and degradation of the receptor have been observed in bladder, skin and oral cancers. |
| Commentary on involvement of protein in cancer: | S249 - S249C in KERSEB, bladder cancer, cervical cancer and TD1. S249 is located between the Ig-like C2 type domain (AA 151-244) and the Ig-like C2 type domain (AA253-355); K650 - K650 E in KERSEB, TD2, TEST and bladder cancer samples; bladder transitional cell carcinoma; somatic mutation; constitutively activated kinase with impaired internalization and degradation, resulting in prolonged FGFR3 signaling. K650M in KERSEB, ACH and TD1; constitutively activated kinase with impaired internalization and degradation, resulting in prolonged FGFR3 signaling. K650Q in hypochondroplasia and bladder cancer; in hypochondroplasia the form is milder than that seen in individuals with the K-540 or M-650 mutations. K650 is located in the kinase catalytic domain in the activation loop between subdomains VII and VIII. |