Human Gene PDGFRA (ENST00000257290.10) from GENCODE V44
Description: Homo sapiens platelet derived growth factor receptor alpha (PDGFRA), transcript variant 1, mRNA. (from RefSeq NM_006206) RefSeq Summary (NM_006206): This gene encodes a cell surface tyrosine kinase receptor for members of the platelet-derived growth factor family. These growth factors are mitogens for cells of mesenchymal origin. The identity of the growth factor bound to a receptor monomer determines whether the functional receptor is a homodimer or a heterodimer, composed of both platelet-derived growth factor receptor alpha and beta polypeptides. Studies suggest that this gene plays a role in organ development, wound healing, and tumor progression. Mutations in this gene have been associated with idiopathic hypereosinophilic syndrome, somatic and familial gastrointestinal stromal tumors, and a variety of other cancers. [provided by RefSeq, Mar 2012]. Gencode Transcript: ENST00000257290.10 Gencode Gene: ENSG00000134853.12 Transcript (Including UTRs) Position: hg38 chr4:54,229,293-54,298,245 Size: 68,953 Total Exon Count: 23 Strand: + Coding Region Position: hg38 chr4:54,258,769-54,295,272 Size: 36,504 Coding Exon Count: 22
ID:PGFRA_HUMAN DESCRIPTION: RecName: Full=Platelet-derived growth factor receptor alpha; Short=PDGF-R-alpha; Short=PDGFR-alpha; EC=2.7.10.1; AltName: Full=Alpha platelet-derived growth factor receptor; AltName: Full=Alpha-type platelet-derived growth factor receptor; AltName: Full=CD140 antigen-like family member A; AltName: Full=CD140a antigen; AltName: Full=Platelet-derived growth factor alpha receptor; AltName: Full=Platelet-derived growth factor receptor 2; Short=PDGFR-2; AltName: CD_antigen=CD140a; Flags: Precursor; 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. CATALYTIC ACTIVITY: ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate. ENZYME REGULATION: Present in an inactive conformation in the absence of bound ligand. Binding of PDGFA and/or PDGFB leads to dimerization and activation by autophosphorylation on tyrosine residues. Inhibited by imatinib, nilotinib and sorafenib. SUBUNIT: Interacts with homodimeric PDGFA, PDGFB and PDGFC, and with heterodimers formed by PDGFA and PDGFB. Monomer in the absence of bound ligand. Interaction with dimeric PDGFA, PDGFB and/or PDGFC leads to receptor dimerization, where both PDGFRA homodimers and heterodimers with PDGFRB are observed. Interacts (tyrosine phosphorylated) with SHB (via SH2 domain) (By similarity). Interacts (tyrosine phosphorylated) with SHF (via SH2 domain). Interacts (tyrosine phosphorylated) with SRC (via SH2 domain). Interacts (tyrosine phosphorylated) with PIK3R1. Interacts (tyrosine phosphorylated) with PLCG1 (via SH2 domain). Interacts (tyrosine phosphorylated) with CRK, GRB2 and GRB7. Interacts with human cytomegalovirus/HHV-5 envelop glycoprotein B/gB. SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Note=The activated receptor is rapidly internalized and degraded. 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. PTM: N-glycosylated. PTM: Ubiquitinated, leading to its degradation (Probable). PTM: Autophosphorylated on tyrosine residues upon ligand binding. Autophosphorylation occurs in trans, i.e. one subunit of the dimeric receptor phosphorylates tyrosine residues on the other subunit. Phosphorylation at Tyr-731 and Tyr-742 is important for interaction with PIK3R1. Phosphorylation at Tyr-720 and Tyr-754 is important for interaction with PTPN11. Phosphorylation at Tyr-762 is important for interaction with CRK. Phosphorylation at Tyr-572 and Tyr-574 is important for interaction with SRC and SRC family members. Phosphorylation at Tyr-988 and Tyr-1018 is important for interaction with PLCG1. DISEASE: 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. DISEASE: Defects in PDGFRA are a cause of gastrointestinal stromal tumor (GIST) [MIM:606764]. Note=Mutations that cause constitutive activation of PDGFRA may be a cause of gastrointestinal stromal tumor (GIST). SIMILARITY: Belongs to the protein kinase superfamily. Tyr protein kinase family. CSF-1/PDGF receptor subfamily. SIMILARITY: Contains 5 Ig-like C2-type (immunoglobulin-like) domains. SIMILARITY: Contains 1 protein kinase domain. SEQUENCE CAUTION: Sequence=AAP69563.1; Type=Erroneous initiation; Note=Translation N-terminally shortened;
The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.
ModBase Predicted Comparative 3D Structure on P16234
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Orthologous Genes in Other Species
Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
AY229892 - Homo sapiens FIP1L1/PDGFRA fusion protein (FIP1L1/PDGFRA fusion) mRNA, complete cds; alternatively spliced. AK308353 - Homo sapiens cDNA, FLJ98301. BC015186 - Homo sapiens platelet-derived growth factor receptor, alpha polypeptide, mRNA (cDNA clone IMAGE:4043984), complete cds. M21574 - Human platelet-derived growth factor receptor alpha (PDGFRA) mRNA, complete cds. AK311006 - Homo sapiens cDNA, FLJ18048. AK316578 - Homo sapiens cDNA, FLJ94401, highly similar to Homo sapiens platelet-derived growth factor receptor, alphapolypeptide (PDGFRA), mRNA. M22734 - Human platelet-derived growth factor A type receptor mRNA, complete cds. BC063414 - Homo sapiens platelet-derived growth factor receptor, alpha polypeptide, mRNA (cDNA clone MGC:74795 IMAGE:5205969), complete cds. KJ901630 - Synthetic construct Homo sapiens clone ccsbBroadEn_11024 PDGFRA gene, encodes complete protein. LF211984 - JP 2014500723-A/19487: Polycomb-Associated Non-Coding RNAs. MA447561 - JP 2018138019-A/19487: Polycomb-Associated Non-Coding RNAs. M30494 - Human platelet-derived growth factor receptor alpha (PDGFRA) mRNA fragment. JD540650 - Sequence 521674 from Patent EP1572962. LC424350 - Homo sapiens Kasumi-1 PDGFRA mRNA for platelet-derived growth factor receptor alpha, partial cds, exon1gamma-exon2-exon3. LC424351 - Homo sapiens KMS26 PDGFRA mRNA for platelet-derived growth factor receptor alpha, partial cds, exon1delta-exon2-exon3. LC424352 - Homo sapiens RPMI8226 PDGFRA mRNA for platelet-derived growth factor receptor alpha, partial cds, exon1epsilon-exon2-exon3. LC424353 - Homo sapiens ARH77 PDGFRA mRNA for platelet-derived growth factor receptor alpha, partial cds, exon1zeta-exon2-exon3. LC424354 - Homo sapiens KG-1 PDGFRA mRNA for platelet-derived growth factor receptor alpha, partial cds, exon1eta-exon2-exon3. LQ726438 - Sequence 16 from Patent WO2018094385. L25829 - Human platelet-derived growth factor alpha-receptor (PDGFRA) mRNA, exons 13-16. X76079 - H.sapiens mRNA for platelet derived growth factor alpha receptor. JD496394 - Sequence 477418 from Patent EP1572962. JD553576 - Sequence 534600 from Patent EP1572962. JD530045 - Sequence 511069 from Patent EP1572962. JD046645 - Sequence 27669 from Patent EP1572962. JD339096 - Sequence 320120 from Patent EP1572962. JD546152 - Sequence 527176 from Patent EP1572962. JD262939 - Sequence 243963 from Patent EP1572962. JD060812 - Sequence 41836 from Patent EP1572962. JD303329 - Sequence 284353 from Patent EP1572962. JD168070 - Sequence 149094 from Patent EP1572962. JD146959 - Sequence 127983 from Patent EP1572962. JD103128 - Sequence 84152 from Patent EP1572962. JD376552 - Sequence 357576 from Patent EP1572962. JD450639 - Sequence 431663 from Patent EP1572962. JD415421 - Sequence 396445 from Patent EP1572962. JD238629 - Sequence 219653 from Patent EP1572962. JD042200 - Sequence 23224 from Patent EP1572962. JD528507 - Sequence 509531 from Patent EP1572962. JD248492 - Sequence 229516 from Patent EP1572962. JD093571 - Sequence 74595 from Patent EP1572962. JD296416 - Sequence 277440 from Patent EP1572962. JD510801 - Sequence 491825 from Patent EP1572962. JD429163 - Sequence 410187 from Patent EP1572962. MP414202 - Sequence 16 from Patent WO2019222178. MC019442 - JP 2020500514-A/16: CHEMICAL COMPOSITIONS AND METHODS OF USING SAME.
Biochemical and Signaling Pathways
KEGG - Kyoto Encyclopedia of Genes and Genomes hsa04010 - MAPK signaling pathway hsa04020 - Calcium signaling pathway hsa04060 - Cytokine-cytokine receptor interaction hsa04144 - Endocytosis hsa04510 - Focal adhesion hsa04540 - Gap junction hsa04810 - Regulation of actin cytoskeleton hsa05200 - Pathways in cancer hsa05214 - Glioma hsa05215 - Prostate cancer hsa05218 - Melanoma
BioCarta from NCI Cancer Genome Anatomy Project h_rac1Pathway - Rac 1 cell motility signaling pathway h_erkPathway - Erk1/Erk2 Mapk Signaling pathway h_pdgfPathway - PDGF Signaling Pathway h_cblPathway - CBL mediated ligand-induced downregulation of EGF receptors h_edg1Pathway - Phospholipids as signalling intermediaries h_cdc42racPathway - Role of PI3K subunit p85 in regulation of Actin Organization and Cell Migration
Reactome (by CSHL, EBI, and GO)
Protein P16234 (Reactome details) participates in the following event(s):
R-HSA-389086 Autophosphorylation of PDGF alpha/beta receptors R-HSA-389083 Autophosphorylation of PDGF alpha receptors R-HSA-8864036 PTPN12 dephosphorylates PDGFRB at Y1021 R-HSA-186765 PLC-gamma binds to the active receptor R-HSA-186778 SHP2 binds to the active receptor R-HSA-186780 PI3-kinase binds to the active receptor R-HSA-186819 SH2 domain of Src binds to the active receptor R-HSA-186826 Grb2/Sos1 complex binds to the active receptor R-HSA-380782 STAT binds to the active receptor R-HSA-382055 Grb7 binds to the active PDGF receptor R-HSA-382056 Crk binds to the active PDGF receptor R-HSA-382058 Nck binds to the active PDGF receptor R-HSA-1524182 Activated PLC gamma dissociates from the PDGF receptor R-HSA-380780 Activation of Src R-HSA-1524186 Phosphorylation of PLCgamma by PDGFR R-HSA-382052 p130Cas and C3G bind PDGFR bound Crk R-HSA-186800 PI3K catalyses the phosphorylation of PIP2 to PIP3 R-HSA-186834 Sos-mediated nucleotide exchange of Ras (PDGF receptor:Grb2:Sos) R-HSA-2400009 PI3K inhibitors block PI3K catalytic activity R-HSA-2316434 PI3K phosphorylates PIP2 to PIP3 R-HSA-5672965 RAS GEFs promote RAS nucleotide exchange R-HSA-186797 Signaling by PDGF R-HSA-9006934 Signaling by Receptor Tyrosine Kinases R-HSA-162582 Signal Transduction R-HSA-186763 Downstream signal transduction R-HSA-2219530 Constitutive Signaling by Aberrant PI3K in Cancer R-HSA-1257604 PIP3 activates AKT signaling R-HSA-6811558 PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling R-HSA-5673001 RAF/MAP kinase cascade R-HSA-2219528 PI3K/AKT Signaling in Cancer R-HSA-9006925 Intracellular signaling by second messengers R-HSA-199418 Negative regulation of the PI3K/AKT network R-HSA-5684996 MAPK1/MAPK3 signaling R-HSA-5663202 Diseases of signal transduction R-HSA-5683057 MAPK family signaling cascades R-HSA-1643685 Disease
US Server
