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: | PDGFRA |
| Gene Name: | PDGFRA |
| Protein Full Name: | Alpha-type platelet-derived growth factor receptor |
| Alias: | Alpha platelet-derived growth factor receptor precursor; CD140a; EC 2.7.10.1; Kinase PDGFR-alpha; PDGFR2; PDGFRa; PDGFR-alpha; PDGF-R-alpha; PGFRA; Platelet-derived growth factor receptor, alpha polypeptide; Platelet-derived growth factor, alpha-receptor |
| Mass (Da): | 122670 |
| Number AA: | 1089 |
| UniProt ID: | P16234 |
| Locus ID: | 5156 |
| COSMIC ID: | PDGFRA |
| Gene location on chromosome: | 4q12 |
| Cancer protein type: | OP |
| Effect of cancer mutation on protein: | GAIN |
| Effect of active protein on cancer: | PROMOTES |
| Number of cancer specimens: | 40354 |
| Percent of cancer specimens with mutations: | 4.3 |
| General distribution of mutations: | Narrow |
| Location of most mutations: | Two main regions, one (AA 560-563) with point mutations, complex mutations, deletions and insertions, the other (AA 841-845) with point mutations, complex mutations, and deletions. |
| Commonly recorded point mutations: | D842V (482); V561D (59) |
| Deregulated in translocations: | Chronic Myeloid Leukemia, Fusion partners include BCR. |
| Normal role description: | PDGFRA is a receptor-tyrosine kinase that is activated upon binding platelet-derived growth factor (PDGF). Ligand binding causes dimerization of the receptor to activate signalling cascades to activate effector substrates such as PIK3R1, PLCG1, and PTPN11. Effector substrates will cause release of calcium from endoplasmic reticulum, by PLCG1, and activation of AKT1, by PIK3R1. This ultimately leads to growth and proliferation in cells by the MAPK and STAT transcription factor activation. PDGFRA is negatively regulated by protein phosphatases to cause inactivation and internalization. Due to PDGFRA's role in cellular growth its dysfunction may lead tumourigenesis. A high number of gastrointestinal stromal tumours have been implicated in PDGFRA dysfunction and constitutive activation. Typically mis-sense or deletion mutations were found to cause constitutively activated PDGFRA. Furthermore, a fusion protein of PDGFRA with BCR can arise from a translocation event with the PDGFRA gene locus. This fusion protein has been implicated in the development of chronic myeloid leukemias. |
| Commentary on involvement of protein in cancer: | V561D in a GIST sample; constitutively activated kinase. V561 is located just after the transmembrane domain. 842-845 - Missing in a GIST sample; constitutively activated kinase. D842V in a GIST sample; imatinib resistant, constitutively activated kinase. D842Y in a GIST sample; imatinib sensitive, constitutively activated kinase. Y842F: No effect on autophosphorylation and phosphorylation of PLCG1. Abolishes activation of phosphatidylinositol 3-kinase. D842 is located in the catalytic domain of the kinase in the activation loop just after Subdomain VII.. Unclassified categories. Small Intestine; Carcinoma; TRUE (30%); (40/132); Complex Inframe Deletions; Insertion inframe; Mis-sense. Soft Tissues; Synovial Sarcoma; TRUE (7%); (2/28); Deletion Inframe. Soft Tissues; malignant peripheral nerve sheath tumour; TRUE (3%); (2/61); Mis-sense. Less than 3% mutations in autonomic ganglia, bone CNS, hematopoietic/lymphoid tissue, lung, ovary, prostate and skin. |