Molecular Target Synopsis
Overview
Domains and Structures
Drugs and Clinical Candidates
Druggability
Chemistry
Ligand Efficiency Plot
Pathways
Family Cladogram
Interaction Network
Gene Expression
Gene Copy Number Variation
RNAi
Mutations
Germline Genetics

PDGFRA (P16234) - Overview - Molecular Target Synopsis

Protein


PDGFRA, Platelet-derived growth factor receptor alpha
Enzyme Classification 2.7.10.1
UniProt P16234

Also Known as PGFRA_HUMAN, PDGFRA, PDGFR2, RHEPDGFRA

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. 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.

5GRN
CRYSTAL STRUCTURE OF PDGFRA IN COMPLEX WITH WQ-C-159
RCSB/PDB
Inspect Structure
See all 3D Structures for PDGFRA

Isoforms / Transcripts (Protein Coding)


Drugs


PDGFRA is targeted by Approved Drugs Pazopanib, Axitinib, Sunitinib. (see details)
Pazopanib
Axitinib
Sunitinib

Sub-cellular localization


UniProt: PDGFRA is active in the following subcellular-locations: cell membrane, cell projection, cilium, golgi apparatus.
GO terms: PDGFRA is active in the following subcellular-locations: cell junction, cilium, cytoplasm, external side of plasma membrane, Golgi apparatus, integral component of plasma membrane, intrinsic component of plasma membrane, membrane, microvillus, nucleus, plasma membrane, protein-containing complex, receptor complex.



UniProt
GO terms

Gene Copy Number Variation


In COSMIC - Cell Lines Project PDGFRA has gain in 8 cell-lines, loss in 4 cell-lines and no signal in 993 cell-lines. (see details)

Gene Expression


In NCI60, the highest expressing cell lines are: SNB_75, U251, SNB_19

In Array Express (RNA-seq of 675 commonly used human cancer cell lines), the highest expressing cell lines are: Hs 675.T, NCI-H1703, G-402

In Array Express (RNA-seq of long poly adenylated RNA and long non poly adenylated RNA from ENCODE cell lines), the highest expressing cell lines are: NHLF, AG445, BJ

(see details)

RNA Interference


PDGFRA was reported in the following RNAI studies:

Cell - Large Scale Profiling of Kinase Dependencies in Cancer Cell Lines, the highest RNAi cell lines are: OAW42, MDAMB453. (see details)

3D Structures


For PDGFRA there are:
2 structures (2 chains) solved
1 are solved in complex with at least one small molecule ligand



(see details)
Molecular Target 3D Synopsis

Screening and Chemistry


PDGFRA has been screened with 1762 compounds (4736 bioactivities), 370 compounds have bioactivities that show binding affinity of <= 500nM (447 bioactivities). (see details)