InnateDB Protein
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IDBP-479386.4
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Last Modified
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2014-10-13 [Report errors or provide feedback]
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Gene Symbol
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PDGFRA
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Protein Name
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platelet-derived growth factor receptor, alpha polypeptide
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Synonyms
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CD140A; PDGFR-2; PDGFR2; RHEPDGFRA;
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Species
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Homo sapiens
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Ensembl Protein
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ENSP00000425648
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InnateDB Gene
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IDBG-18854 (PDGFRA)
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Protein Structure
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Function |
Tyrosine-protein kinase that acts as a cell-surface receptor for PDGFA, PDGFB and PDGFC and plays an essential role in the regulation of embryonic development, cell proliferation, survival and chemotaxis. Depending on the context, promotes or inhibits cell proliferation and cell migration. Plays an important role in the differentiation of bone marrow-derived mesenchymal stem cells. Required for normal skeleton development and cephalic closure during embryonic development. Required for normal development of the mucosa lining the gastrointestinal tract, and for recruitment of mesenchymal cells and normal development of intestinal villi. Plays a role in cell migration and chemotaxis in wound healing. Plays a role in platelet activation, secretion of agonists from platelet granules, and in thrombin-induced platelet aggregation. Binding of its cognate ligands - homodimeric PDGFA, homodimeric PDGFB, heterodimers formed by PDGFA and PDGFB or homodimeric PDGFC -leads to the activation of several signaling cascades; the response depends on the nature of the bound ligand and is modulated by the formation of heterodimers between PDGFRA and PDGFRB. Phosphorylates PIK3R1, PLCG1, and PTPN11. Activation of PLCG1 leads to the production of the cellular signaling molecules diacylglycerol and inositol 1,4,5-trisphosphate, mobilization of cytosolic Ca(2+) and the activation of protein kinase C. Phosphorylates PIK3R1, the regulatory subunit of phosphatidylinositol 3-kinase, and thereby mediates activation of the AKT1 signaling pathway. Mediates activation of HRAS and of the MAP kinases MAPK1/ERK2 and/or MAPK3/ERK1. Promotes activation of STAT family members STAT1, STAT3 and STAT5A and/or STAT5B. Receptor signaling is down-regulated by protein phosphatases that dephosphorylate the receptor and its down-stream effectors, and by rapid internalization of the activated receptor. {ECO:0000269PubMed:10734113, ECO:0000269PubMed:10947961, ECO:0000269PubMed:11297552, ECO:0000269PubMed:12522257, ECO:0000269PubMed:1646396, ECO:0000269PubMed:1709159, ECO:0000269PubMed:17141222, ECO:0000269PubMed:20972453, ECO:0000269PubMed:21224473, ECO:0000269PubMed:21596750, ECO:0000269PubMed:2554309, ECO:0000269PubMed:8188664, ECO:0000269PubMed:8760137, ECO:0000269PubMed:8943348}.
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Subcellular Localization |
Cell membrane {ECO:0000269PubMed:14644164, ECO:0000269PubMed:2554309, ECO:0000269PubMed:8188664}; Single- pass type I membrane protein {ECO:0000269PubMed:14644164, ECO:0000269PubMed:2554309, ECO:0000269PubMed:8188664}. Note=The activated receptor is rapidly internalized and degraded.
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Disease Associations |
Note=A chromosomal aberration involving PDGFRA is found in some cases of hypereosinophilic syndrome. Interstitial chromosomal deletion del(4)(q12q12) causes the fusion of FIP1L1 and PDGFRA (FIP1L1-PDGFRA). Mutations that cause overexpression and/or constitutive activation of PDGFRA may be a cause of hypereosinophilic syndrome. {ECO:0000269PubMed:12808148}.Gastrointestinal stromal tumor (GIST) [MIM:606764]: Common mesenchymal neoplasms arising in the gastrointestinal tract, most often in the stomach. They are histologically, immunohistochemically, and genetically different from typical leiomyomas, leiomyosarcomas, and schwannomas. Most GISTs are composed of a fairly uniform population of spindle-shaped cells. Some tumors are dominated by epithelioid cells or contain a mixture of spindle and epithelioid morphologies. Primary GISTs in the gastrointestinal tract commonly metastasize in the omentum and mesenteries, often as multiple nodules. However, primary tumors may also occur outside of the gastrointestinal tract, in other intra-abdominal locations, especially in the omentum and mesentery. {ECO:0000269PubMed:12522257, ECO:0000269PubMed:15928335}. Note=The gene represented in this entry may be involved in disease pathogenesis. Mutations causing PDGFRA constitutive activation have been found in gastrointestinal stromal tumors lacking KIT mutations (PubMed:12522257). {ECO:0000269PubMed:12522257}.
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Tissue Specificity |
Detected in platelets (at protein level). Widely expressed. Detected in brain, fibroblasts, smooth muscle, heart, and embryo. Expressed in primary and metastatic colon tumors and in normal colon tissue. {ECO:0000269PubMed:2536956, ECO:0000269PubMed:7896447, ECO:0000269PubMed:8188664}.
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Comments |
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Number of Interactions
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This gene and/or its encoded proteins are associated with 52 experimentally validated interaction(s) in this database.
They are also associated with 2 interaction(s) predicted by orthology.
Experimentally validated |
Total |
52
[view]
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Protein-Protein |
52
[view]
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Protein-DNA |
0
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Protein-RNA |
0
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DNA-DNA |
0
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RNA-RNA |
0
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DNA-RNA |
0
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Predicted by orthology |
Total |
2 [view]
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Molecular Function |
Accession |
GO Term |
GO:0004714
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transmembrane receptor protein tyrosine kinase activity
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GO:0005018
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platelet-derived growth factor alpha-receptor activity
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GO:0005021
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vascular endothelial growth factor-activated receptor activity
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GO:0005161
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platelet-derived growth factor receptor binding
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GO:0005515
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protein binding
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GO:0005524
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ATP binding
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GO:0038085
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vascular endothelial growth factor binding
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GO:0042803
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protein homodimerization activity
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GO:0048407
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platelet-derived growth factor binding
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Biological Process |
GO:0001553
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luteinization
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GO:0001775
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cell activation
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GO:0007173
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epidermal growth factor receptor signaling pathway
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GO:0007204
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positive regulation of cytosolic calcium ion concentration
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GO:0008284
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positive regulation of cell proliferation
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GO:0008543
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fibroblast growth factor receptor signaling pathway
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GO:0010544
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negative regulation of platelet activation
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GO:0010863
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positive regulation of phospholipase C activity
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GO:0014068
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positive regulation of phosphatidylinositol 3-kinase signaling
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GO:0016032
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viral process
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GO:0018108
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peptidyl-tyrosine phosphorylation
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GO:0030335
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positive regulation of cell migration
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GO:0035790
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platelet-derived growth factor receptor-alpha signaling pathway
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GO:0038091
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positive regulation of cell proliferation by VEGF-activated platelet derived growth factor receptor signaling pathway
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GO:0038095
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Fc-epsilon receptor signaling pathway
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GO:0042060
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wound healing
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GO:0043552
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positive regulation of phosphatidylinositol 3-kinase activity
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GO:0045087
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innate immune response
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GO:0045740
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positive regulation of DNA replication
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GO:0046777
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protein autophosphorylation
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GO:0048008
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platelet-derived growth factor receptor signaling pathway
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GO:0048011
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neurotrophin TRK receptor signaling pathway
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GO:0048015
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phosphatidylinositol-mediated signaling
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GO:0048146
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positive regulation of fibroblast proliferation
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GO:0048557
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embryonic digestive tract morphogenesis
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GO:0048701
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embryonic cranial skeleton morphogenesis
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GO:0048704
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embryonic skeletal system morphogenesis
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GO:0050920
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regulation of chemotaxis
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GO:0055003
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cardiac myofibril assembly
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GO:0060326
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cell chemotaxis
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GO:0061298
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retina vasculature development in camera-type eye
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GO:0070374
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positive regulation of ERK1 and ERK2 cascade
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GO:0070527
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platelet aggregation
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GO:0072277
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metanephric glomerular capillary formation
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GO:2000249
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regulation of actin cytoskeleton reorganization
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GO:2000739
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regulation of mesenchymal stem cell differentiation
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Cellular Component |
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PDB ID |
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InterPro |
IPR003599
Immunoglobulin subtype
IPR007110
Immunoglobulin-like domain
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PFAM |
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PRINTS |
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PIRSF |
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SMART |
SM00409
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TIGRFAMs |
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Modification |
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SwissProt |
P16234
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PhosphoSite |
PhosphoSite-P16234
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TrEMBL |
D6RIG5
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UniProt Splice Variant |
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Entrez Gene |
5156
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UniGene |
Hs.74615
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RefSeq |
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HUGO |
HGNC:8803
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OMIM |
173490
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CCDS |
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HPRD |
01429
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IMGT |
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EMBL |
AC098587
AC138779
AK316578
AY229892
BC015186
BC063414
D50017
M21574
M22734
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GenPept |
AAA60048
AAA96715
AAH15186
AAH63414
AAP69563
BAA08742
BAG38166
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