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: | FLT1 |
| Gene Name: | FLT1 |
| Protein Full Name: | Vascular endothelial growth factor receptor 1 |
| Alias: | EC 2.7.1.112; EC 2.7.10.1; FLT; Flt-1; Fms-like tyrosine kinase 1; Fms-related tyrosine kinase 1; FRT; Tyrosine-protein kinase FRT; Tyrosine-protein kinase receptor FLT; Vascular endothelial growth factor receptor 1; Vascular endothelial growth factor/vascular permeability factor receptor; Vascular permeability factor receptor; VGFR1 |
| Mass (Da): | 150769 |
| Number AA: | 1338 |
| UniProt ID: | P17948 |
| Locus ID: | 2321 |
| COSMIC ID: | FLT1 |
| Gene location on chromosome: | 13q12.2-q12.3 |
| Cancer protein type: | OP |
| Effect of cancer mutation on protein: | GAIN |
| Effect of active protein on cancer: | PROMOTES |
| Number of cancer specimens: | 20667 |
| Percent of cancer specimens with mutations: | 1.74 |
| General distribution of mutations: | Multi-site |
| Location of most mutations: | Broad distribution of mutation sites with many point mutations and 1 insertion across entire protein, but no complex mutations or deletions. |
| Normal role description: | FLT1 is a receptor-tyrosine kinase that is activated upon binding with VEGF-A, VEGF-B and PGF. It plays an important role in the development of embryonic vasculature, and as a negative regulator of embryonic angiogenesis by inhibiting excessive proliferation of endothelial cells. However, it can promote PGF-mediated endothelial cell proliferation, survival and angiogenesis in adults, although this seems to be cell-type specific. It also contributes to cancer cell survival, proliferation, migration, and invasion, as well as tumour angiogenesis, metastasis, and recruitment of tumour-infiltrating macrophages. It has a very high affinity for VEGF-A and may function as a negative regulator of VEGF-A signalling by limiting the amount of free VEGF-A and preventing its binding to KDR. Isoforms lacking a transmembrane domain may function as decoy receptors for VEGF-A. Furthermore, it mediates phosphorylation of PI3K, leading to activation of the downstream signalling pathway, as well as mediating the activation of the MAPK signalling pathway, and of the Akt/PKB signalling pathway. |
| Commentary on involvement of protein in cancer: | L1061V(1) is the one of the only mutation noted within the kinase activation loop between subdomains VII and VIII. Only 2 bladder cancer samples were included in Sanger COSMIC; 1 laryngeal-, 1/201 breast cancer- and 5/477 CNS samples were also mutated. |