InnateDB: Systems Biology of the Innate Immune Response

Mus musculus Protein: Pdgfra

Summary

InnateDB Protein

IDBP-171931.6

Last Modified

2014-10-13 [Report errors or provide feedback]

Gene Symbol

Pdgfra

Protein Name

platelet derived growth factor receptor, alpha polypeptide

Synonyms

AI115593; CD140a; Pdgfr-2;

Species

Mus musculus

Ensembl Protein

ENSMUSP00000000476

InnateDB Gene

IDBG-171929 (Pdgfra)

Protein Structure

UniProt Annotation

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:10903171, ECO:0000269PubMed:19030102, ECO:0000269PubMed:20110689, ECO:0000269PubMed:9226440}.

Subcellular Localization

Cell membrane; Single-pass type I membrane protein. Note=The activated receptor is rapidly internalized and degraded. {ECO:0000250}.

Disease Associations

Tissue Specificity

Focally expressed in cortical interstitial cells and highly expressed in the interstitium of the papillary region. Also expressed by adventitial cells in arterial vessels. Up-regulated in areas of renal fibrosis. In mice with unilateral ureteral obstruction, expression in cortical interstitial cells becomes prominent at day 4 which increases progressively until day 14. {ECO:0000269PubMed:14514732}.

Comments

Interactions

Number of Interactions

This gene and/or its encoded proteins are associated with 5 experimentally validated interaction(s) in this database.
They are also associated with 22 interaction(s) predicted by orthology.

Experimentally validated
Total	5 [view]
Protein-Protein	5 [view]
Protein-DNA	0
Protein-RNA	0
DNA-DNA	0
RNA-RNA	0
DNA-RNA	0

Predicted by orthology
Total	22 [view]

Gene Ontology

Molecular Function

Accession	GO Term
GO:0004672	protein kinase activity
GO:0004713	protein tyrosine kinase activity
GO:0004714	transmembrane receptor protein tyrosine kinase activity
GO:0005018	platelet-derived growth factor alpha-receptor activity
GO:0005021	vascular endothelial growth factor-activated receptor activity
GO:0005161	platelet-derived growth factor receptor binding
GO:0005515	protein binding
GO:0005524	ATP binding
GO:0016772	transferase activity, transferring phosphorus-containing groups
GO:0038085	vascular endothelial growth factor binding
GO:0042803	protein homodimerization activity
GO:0048407	platelet-derived growth factor binding

Biological Process

GO:0001553	luteinization
GO:0001701	in utero embryonic development
GO:0002244	hematopoietic progenitor cell differentiation
GO:0006468	protein phosphorylation
GO:0007169	transmembrane receptor protein tyrosine kinase signaling pathway
GO:0007204	positive regulation of cytosolic calcium ion concentration
GO:0008210	estrogen metabolic process
GO:0008284	positive regulation of cell proliferation
GO:0008585	female gonad development
GO:0009653	anatomical structure morphogenesis
GO:0009887	organ morphogenesis
GO:0010544	negative regulation of platelet activation
GO:0010863	positive regulation of phospholipase C activity
GO:0016477	cell migration
GO:0018108	peptidyl-tyrosine phosphorylation
GO:0023019	signal transduction involved in regulation of gene expression
GO:0030198	extracellular matrix organization
GO:0030324	lung development
GO:0030325	adrenal gland development
GO:0030335	positive regulation of cell migration
GO:0030539	male genitalia development
GO:0033327	Leydig cell differentiation
GO:0035790	platelet-derived growth factor receptor-alpha signaling pathway
GO:0038091	positive regulation of cell proliferation by VEGF-activated platelet derived growth factor receptor signaling pathway
GO:0042060	wound healing
GO:0042475	odontogenesis of dentin-containing tooth
GO:0043552	positive regulation of phosphatidylinositol 3-kinase activity
GO:0045740	positive regulation of DNA replication
GO:0046777	protein autophosphorylation
GO:0048008	platelet-derived growth factor receptor signaling pathway
GO:0048015	phosphatidylinositol-mediated signaling
GO:0048146	positive regulation of fibroblast proliferation
GO:0048557	embryonic digestive tract morphogenesis
GO:0048701	embryonic cranial skeleton morphogenesis
GO:0048705	skeletal system morphogenesis
GO:0050920	regulation of chemotaxis
GO:0055003	cardiac myofibril assembly
GO:0060021	palate development
GO:0060325	face morphogenesis
GO:0060326	cell chemotaxis
GO:0061298	retina vasculature development in camera-type eye
GO:0070374	positive regulation of ERK1 and ERK2 cascade
GO:0070527	platelet aggregation
GO:0071230	cellular response to amino acid stimulus
GO:0072277	metanephric glomerular capillary formation
GO:2000739	regulation of mesenchymal stem cell differentiation

Cellular Component

GO:0005634	nucleus
GO:0005737	cytoplasm
GO:0005887	integral component of plasma membrane
GO:0005902	microvillus
GO:0009897	external side of plasma membrane
GO:0009986	cell surface
GO:0016021	integral component of membrane

Protein Structure and Domains

PDB ID

MGI:97530

InterPro

IPR000719 Protein kinase domain
IPR001245 Serine-threonine/tyrosine-protein kinase catalytic domain
IPR002290 Serine/threonine- /dual specificity protein kinase, catalytic domain
IPR003598 Immunoglobulin subtype 2
IPR003599 Immunoglobulin subtype
IPR007110 Immunoglobulin-like domain
IPR011009 Protein kinase-like domain
IPR013098 Immunoglobulin I-set
IPR016243 Tyrosine-protein kinase, CSF-1/PDGF receptor
IPR020635 Tyrosine-protein kinase, catalytic domain

PFAM

PF00069
PF07714
PF07679

PRINTS

PR00109

PIRSF

PIRSF000615
PIRSF500947

SMART

SM00220
SM00408
SM00409
SM00219

TIGRFAMs

Post-translational Modifications

Modification

Cross-References