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Protein

Platelet-derived growth factor receptor alpha

Gene

Pdgfra

Organism
Rattus norvegicus (Rat)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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 Ca2+ 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 (By similarity).By similarity

Catalytic activityi

ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate.PROSITE-ProRule annotation

Enzyme regulationi

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 (By similarity).By similarity

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei626ATPPROSITE-ProRule annotation1
Active sitei817Proton acceptorPROSITE-ProRule annotation1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi598 – 606ATPPROSITE-ProRule annotation9

GO - Molecular functioni

GO - Biological processi

  • aging Source: RGD
  • brain development Source: RGD
  • cardiac myofibril assembly Source: UniProtKB
  • cell chemotaxis Source: UniProtKB
  • cellular response to fibroblast growth factor stimulus Source: RGD
  • cellular response to interleukin-1 Source: RGD
  • embryonic cranial skeleton morphogenesis Source: UniProtKB
  • embryonic digestive tract morphogenesis Source: UniProtKB
  • embryonic skeletal system morphogenesis Source: UniProtKB
  • inner ear development Source: RGD
  • lung growth Source: RGD
  • luteinization Source: UniProtKB
  • male gonad development Source: RGD
  • metanephric glomerular capillary formation Source: UniProtKB
  • negative regulation of platelet activation Source: UniProtKB
  • peptidyl-tyrosine phosphorylation Source: UniProtKB
  • phosphatidylinositol-mediated signaling Source: UniProtKB
  • platelet aggregation Source: UniProtKB
  • platelet-derived growth factor receptor signaling pathway Source: UniProtKB
  • positive regulation of branching involved in lung morphogenesis Source: RGD
  • positive regulation of cell migration Source: UniProtKB
  • positive regulation of cell proliferation Source: RGD
  • positive regulation of cytosolic calcium ion concentration Source: UniProtKB
  • positive regulation of DNA replication Source: UniProtKB
  • positive regulation of ERK1 and ERK2 cascade Source: UniProtKB
  • positive regulation of fibroblast proliferation Source: UniProtKB
  • positive regulation of peptidyl-tyrosine phosphorylation Source: RGD
  • positive regulation of phosphatidylinositol 3-kinase activity Source: UniProtKB
  • protein autophosphorylation Source: UniProtKB
  • regulation of mesenchymal stem cell differentiation Source: UniProtKB
  • response to cytokine Source: RGD
  • response to estradiol Source: RGD
  • response to estrogen Source: RGD
  • response to formaldehyde Source: RGD
  • response to hormone Source: RGD
  • response to hyperoxia Source: RGD
  • response to inorganic substance Source: RGD
  • response to organic substance Source: RGD
  • retina vasculature development in camera-type eye Source: UniProtKB
  • wound healing Source: RGD
Complete GO annotation...

Keywords - Molecular functioni

Developmental protein, Kinase, Receptor, Transferase, Tyrosine-protein kinase

Keywords - Biological processi

Chemotaxis

Keywords - Ligandi

ATP-binding, Nucleotide-binding

Enzyme and pathway databases

BRENDAi2.7.10.1. 5301.

Names & Taxonomyi

Protein namesi
Recommended name:
Platelet-derived growth factor receptor alpha (EC:2.7.10.1)
Short name:
PDGF-R-alpha
Short name:
PDGFR-alpha
Alternative name(s):
Alpha platelet-derived growth factor receptor
Alpha-type platelet-derived growth factor receptor
CD140 antigen-like family member A
Platelet-derived growth factor alpha receptor
CD_antigen: CD140a
Gene namesi
Name:Pdgfra
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
Proteomesi
  • UP000002494 Componenti: Unplaced

Organism-specific databases

RGDi3284. Pdgfra.

Subcellular locationi

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini24 – 527ExtracellularSequence analysisAdd BLAST504
Transmembranei528 – 548HelicalSequence analysisAdd BLAST21
Topological domaini549 – 1088CytoplasmicSequence analysisAdd BLAST540

GO - Cellular componenti

  • axon Source: RGD
  • cytoplasm Source: UniProtKB
  • integral component of plasma membrane Source: UniProtKB
  • nucleus Source: UniProtKB
  • plasma membrane Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Membrane

Pathology & Biotechi

Keywords - Diseasei

Proto-oncogene

Chemistry databases

ChEMBLiCHEMBL2111344.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 23Add BLAST23
ChainiPRO_000001676224 – 1088Platelet-derived growth factor receptor alphaAdd BLAST1065

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Disulfide bondi48 ↔ 99PROSITE-ProRule annotation
Glycosylationi75N-linked (GlcNAc...)Sequence analysis1
Glycosylationi102N-linked (GlcNAc...)Sequence analysis1
Disulfide bondi149 ↔ 188PROSITE-ProRule annotation
Glycosylationi178N-linked (GlcNAc...)Sequence analysis1
Disulfide bondi234 ↔ 289PROSITE-ProRule annotation
Glycosylationi352N-linked (GlcNAc...)Sequence analysis1
Glycosylationi358N-linked (GlcNAc...)Sequence analysis1
Disulfide bondi434 ↔ 500PROSITE-ProRule annotation
Glycosylationi457N-linked (GlcNAc...)Sequence analysis1
Glycosylationi467N-linked (GlcNAc...)Sequence analysis1
Modified residuei571Phosphotyrosine; by autocatalysisBy similarity1
Modified residuei573Phosphotyrosine; by autocatalysisBy similarity1
Modified residuei719Phosphotyrosine; by autocatalysisBy similarity1
Modified residuei730Phosphotyrosine; by autocatalysisBy similarity1
Modified residuei741Phosphotyrosine; by autocatalysisBy similarity1
Modified residuei753Phosphotyrosine; by autocatalysisBy similarity1
Modified residuei761Phosphotyrosine; by autocatalysisBy similarity1
Modified residuei767Phosphotyrosine; by autocatalysisBy similarity1
Modified residuei848Phosphotyrosine; by autocatalysisBy similarity1
Modified residuei987Phosphotyrosine; by autocatalysisBy similarity1
Modified residuei1017Phosphotyrosine; by autocatalysisBy similarity1

Post-translational modificationi

Ubiquitinated, leading to its degradation.By similarity
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-730 and Tyr-741 is important for interaction with PIK3R1. Phosphorylation at Tyr-719 and Tyr-753 is important for interaction with PTPN11. Phosphorylation at Tyr-761 is important for interaction with CRK. Phosphorylation at Tyr-571 and Tyr-573 is important for interaction with SRC and SRC family members. Phosphorylation at Tyr-987 and Tyr-1017 is important for interaction with PLCG1 (By similarity).By similarity

Keywords - PTMi

Disulfide bond, Glycoprotein, Phosphoprotein, Ubl conjugation

Proteomic databases

PaxDbiP20786.
PRIDEiP20786.

PTM databases

iPTMnetiP20786.
PhosphoSitePlusiP20786.

Interactioni

Subunit structurei

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). 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 (By similarity).By similarity

GO - Molecular functioni

  • phosphatidylinositol 3-kinase binding Source: RGD
  • protein homodimerization activity Source: UniProtKB

Protein-protein interaction databases

IntActiP20786. 1 interactor.
MINTiMINT-4589125.
STRINGi10116.ENSRNOP00000003077.

Structurei

3D structure databases

ProteinModelPortaliP20786.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini24 – 112Ig-like C2-type 1Add BLAST89
Domaini116 – 200Ig-like C2-type 2Add BLAST85
Domaini201 – 305Ig-like C2-type 3Add BLAST105
Domaini318 – 409Ig-like C2-type 4Add BLAST92
Domaini413 – 516Ig-like C2-type 5Add BLAST104
Domaini592 – 953Protein kinasePROSITE-ProRule annotationAdd BLAST362

Sequence similaritiesi

Belongs to the protein kinase superfamily. Tyr protein kinase family. CSF-1/PDGF receptor subfamily.PROSITE-ProRule annotation
Contains 1 protein kinase domain.PROSITE-ProRule annotation

Keywords - Domaini

Immunoglobulin domain, Repeat, Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG0200. Eukaryota.
COG0515. LUCA.
HOGENOMiHOG000112009.
HOVERGENiHBG004335.
InParanoidiP20786.
KOiK04363.
PhylomeDBiP20786.

Family and domain databases

Gene3Di2.60.40.10. 4 hits.
InterProiIPR007110. Ig-like_dom.
IPR013783. Ig-like_fold.
IPR013098. Ig_I-set.
IPR003599. Ig_sub.
IPR003598. Ig_sub2.
IPR011009. Kinase-like_dom.
IPR027290. PDGFRA.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR001245. Ser-Thr/Tyr_kinase_cat_dom.
IPR008266. Tyr_kinase_AS.
IPR020635. Tyr_kinase_cat_dom.
IPR016243. Tyr_kinase_CSF1/PDGF_rcpt.
IPR001824. Tyr_kinase_rcpt_3_CS.
[Graphical view]
PANTHERiPTHR24416:SF52. PTHR24416:SF52. 3 hits.
PfamiPF07679. I-set. 2 hits.
PF07714. Pkinase_Tyr. 1 hit.
[Graphical view]
PIRSFiPIRSF500950. Alpha-PDGF_receptor. 1 hit.
PIRSF000615. TyrPK_CSF1-R. 1 hit.
SMARTiSM00409. IG. 4 hits.
SM00408. IGc2. 3 hits.
SM00220. S_TKc. 1 hit.
SM00219. TyrKc. 1 hit.
[Graphical view]
SUPFAMiSSF48726. SSF48726. 4 hits.
SSF56112. SSF56112. 2 hits.
PROSITEiPS50835. IG_LIKE. 3 hits.
PS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00109. PROTEIN_KINASE_TYR. 1 hit.
PS00240. RECEPTOR_TYR_KIN_III. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

P20786-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MGTSQAFLVL SCLLTGPSLI VCQLLLPSIL PNENEKIVPL SSSFSLRCFG
60 70 80 90 100
ESEVSWQHPM SEEEDPNVEI RTEENNSSLF VTVLEVVNAS AAHTGWYTCY
110 120 130 140 150
YNHTQTEESE IEGRHIYIYV PDPDMAFVPL GMTDSLVIVE EDDSAIIPCL
160 170 180 190 200
TTDPDTEVTL HNNGRLVPAS YDSRQGFNGT FSVGPYICEA TVRGRTFKTS
210 220 230 240 250
EFNVYALKAT SELNLEMDTR QTVYKAGETI VVTCAVFNNE VVDLQWTYPG
260 270 280 290 300
EVRNKGITML EEIKLPSIKL VYTLTVPKAT VKDSGDYECA ARQATKEVKE
310 320 330 340 350
MKTVTISVHE KGFVQIRPTF GHLETVNLHQ VREFVVEVQA YPTPRISWLK
360 370 380 390 400
DNLTLIENLT EITTDVQRSQ ETRYQSKLKL IRAKEEDSGH YTIIVQNDDD
410 420 430 440 450
MKSYTFELST LVPASILELV DDHHGSGGGQ TVRCTAEGTP LPNIEWMICK
460 470 480 490 500
DIKKCNNDTS WTVLASNVSN IITEFHQRGR STVEGRVSFA KVEETIAVRC
510 520 530 540 550
LAKNDLGIGN RELKLVAPSL RSELTVAAAV LVLLVIVIVS LIVLVVIWKQ
560 570 580 590 600
KPRYEIRWRV IESISPDGHE YIYVDPMQLP YDSRWEFPRD GLVLGRILGS
610 620 630 640 650
GAFGKVVEGT AYGLSRSQPV MKVAVKMLKP TARSSEKQAL MSELKIMTHL
660 670 680 690 700
GPHLNIVNLL GACTKSGPIY IITEYCFYGD LVNYLHKNRD SFMSRHPEKP
710 720 730 740 750
KKDLDIFGLN PADESTRSYV ILSFENNGDY VDMKQADTTQ YVPMLERKEV
760 770 780 790 800
SKYSDIQRSL YDRPASYKKK SMLDSEAKNL LSDDDSEGLT LLDLLSFTYQ
810 820 830 840 850
VARGMEFLAS KNCVHRDLAA RNVLLAQGKI VKICDFGLAR DIMHDSNYVS
860 870 880 890 900
KGSTFLPVKW MAPESIFDNL YTTLSDVWSY GVLLWEIFSL GGTPYPGMMV
910 920 930 940 950
DSTFYNKIKS GYRMAKPDHA TSEVYEIMVQ CWNSEPEKRP SFYHLSEIVE
960 970 980 990 1000
NLLPGQYKKS YEKIHLDFLK SDHPAVARMR VDSDNAYIGV TYKNEEDKLK
1010 1020 1030 1040 1050
EWEGGLDEQR LSADSGYIIP LPDIDPVPEE EDLGKRNRHS SQTSEESAIE
1060 1070 1080
TGSSSSTFIK REDETIEDID MMDDIGIDSS DLVEDSFL
Length:1,088
Mass (Da):122,642
Last modified:May 1, 1992 - v2
Checksum:i590C8BB0418801E7
GO

Sequence cautioni

The sequence AAA40743 differs from that shown. Reason: Erroneous initiation.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti150L → R in CAA78488 (PubMed:8318539).Curated1
Sequence conflicti519S → T in CAA78488 (PubMed:8318539).Curated1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M63837 mRNA. Translation: AAA40743.1. Different initiation.
Z14118 mRNA. Translation: CAA78488.1.
PIRiA34710. PFRTGA.
RefSeqiNP_036934.1. NM_012802.1.
UniGeneiRn.55127.

Genome annotation databases

GeneIDi25267.
KEGGirno:25267.
UCSCiRGD:3284. rat.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M63837 mRNA. Translation: AAA40743.1. Different initiation.
Z14118 mRNA. Translation: CAA78488.1.
PIRiA34710. PFRTGA.
RefSeqiNP_036934.1. NM_012802.1.
UniGeneiRn.55127.

3D structure databases

ProteinModelPortaliP20786.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

IntActiP20786. 1 interactor.
MINTiMINT-4589125.
STRINGi10116.ENSRNOP00000003077.

Chemistry databases

ChEMBLiCHEMBL2111344.

PTM databases

iPTMnetiP20786.
PhosphoSitePlusiP20786.

Proteomic databases

PaxDbiP20786.
PRIDEiP20786.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

GeneIDi25267.
KEGGirno:25267.
UCSCiRGD:3284. rat.

Organism-specific databases

CTDi5156.
RGDi3284. Pdgfra.

Phylogenomic databases

eggNOGiKOG0200. Eukaryota.
COG0515. LUCA.
HOGENOMiHOG000112009.
HOVERGENiHBG004335.
InParanoidiP20786.
KOiK04363.
PhylomeDBiP20786.

Enzyme and pathway databases

BRENDAi2.7.10.1. 5301.

Miscellaneous databases

PROiP20786.

Family and domain databases

Gene3Di2.60.40.10. 4 hits.
InterProiIPR007110. Ig-like_dom.
IPR013783. Ig-like_fold.
IPR013098. Ig_I-set.
IPR003599. Ig_sub.
IPR003598. Ig_sub2.
IPR011009. Kinase-like_dom.
IPR027290. PDGFRA.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR001245. Ser-Thr/Tyr_kinase_cat_dom.
IPR008266. Tyr_kinase_AS.
IPR020635. Tyr_kinase_cat_dom.
IPR016243. Tyr_kinase_CSF1/PDGF_rcpt.
IPR001824. Tyr_kinase_rcpt_3_CS.
[Graphical view]
PANTHERiPTHR24416:SF52. PTHR24416:SF52. 3 hits.
PfamiPF07679. I-set. 2 hits.
PF07714. Pkinase_Tyr. 1 hit.
[Graphical view]
PIRSFiPIRSF500950. Alpha-PDGF_receptor. 1 hit.
PIRSF000615. TyrPK_CSF1-R. 1 hit.
SMARTiSM00409. IG. 4 hits.
SM00408. IGc2. 3 hits.
SM00220. S_TKc. 1 hit.
SM00219. TyrKc. 1 hit.
[Graphical view]
SUPFAMiSSF48726. SSF48726. 4 hits.
SSF56112. SSF56112. 2 hits.
PROSITEiPS50835. IG_LIKE. 3 hits.
PS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00109. PROTEIN_KINASE_TYR. 1 hit.
PS00240. RECEPTOR_TYR_KIN_III. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiPGFRA_RAT
AccessioniPrimary (citable) accession number: P20786
Entry historyi
Integrated into UniProtKB/Swiss-Prot: February 1, 1991
Last sequence update: May 1, 1992
Last modified: November 2, 2016
This is version 161 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.