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Protein

Platelet-derived growth factor receptor alpha

Gene

PDGFRA

Organism
Homo sapiens (Human)
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.14 Publications

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.3 Publications

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sitei578 – 579Breakpoint for interstitial deletion to form the FIP1L1-PDGFRA fusion protein2
Binding sitei627ATPPROSITE-ProRule annotation1
Active sitei818Proton acceptorPROSITE-ProRule annotation1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi599 – 607ATPPROSITE-ProRule annotation9

GO - Molecular functioni

  • ATP binding Source: UniProtKB-KW
  • phosphatidylinositol-4,5-bisphosphate 3-kinase activity Source: Reactome
  • platelet-derived growth factor alpha-receptor activity Source: UniProtKB
  • platelet-derived growth factor binding Source: UniProtKB
  • platelet-derived growth factor receptor binding Source: BHF-UCL
  • protein homodimerization activity Source: BHF-UCL
  • protein kinase activity Source: MGI
  • Ras guanyl-nucleotide exchange factor activity Source: Reactome
  • transmembrane receptor protein tyrosine kinase activity Source: UniProtKB
  • vascular endothelial growth factor-activated receptor activity Source: BHF-UCL
  • vascular endothelial growth factor binding Source: BHF-UCL

GO - Biological processi

  • cardiac myofibril assembly Source: UniProtKB
  • cell activation Source: BHF-UCL
  • cell chemotaxis Source: UniProtKB
  • cellular response to reactive oxygen species Source: MGI
  • embryonic cranial skeleton morphogenesis Source: UniProtKB
  • embryonic digestive tract morphogenesis Source: UniProtKB
  • embryonic skeletal system morphogenesis Source: UniProtKB
  • luteinization Source: UniProtKB
  • MAPK cascade Source: Reactome
  • 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-alpha signaling pathway Source: UniProtKB
  • platelet-derived growth factor receptor signaling pathway Source: BHF-UCL
  • positive regulation of cell migration Source: UniProtKB
  • positive regulation of cell proliferation Source: UniProtKB
  • positive regulation of cell proliferation by VEGF-activated platelet derived growth factor receptor signaling pathway Source: BHF-UCL
  • positive regulation of cytosolic calcium ion concentration Source: UniProtKB
  • positive regulation of DNA replication Source: BHF-UCL
  • positive regulation of ERK1 and ERK2 cascade Source: UniProtKB
  • positive regulation of fibroblast proliferation Source: BHF-UCL
  • positive regulation of phosphatidylinositol 3-kinase activity Source: UniProtKB
  • positive regulation of phosphatidylinositol 3-kinase signaling Source: UniProtKB
  • positive regulation of phospholipase C activity Source: UniProtKB
  • protein autophosphorylation Source: UniProtKB
  • regulation of actin cytoskeleton reorganization Source: UniProtKB
  • regulation of chemotaxis Source: UniProtKB
  • regulation of mesenchymal stem cell differentiation Source: UniProtKB
  • regulation of phosphatidylinositol 3-kinase signaling Source: Reactome
  • retina vasculature development in camera-type eye Source: UniProtKB
  • viral process Source: UniProtKB-KW
  • wound healing Source: UniProtKB
Complete GO annotation...

Keywords - Molecular functioni

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

Keywords - Biological processi

Chemotaxis, Host-virus interaction

Keywords - Ligandi

ATP-binding, Nucleotide-binding

Enzyme and pathway databases

BioCyciZFISH:HS05923-MONOMER.
BRENDAi2.7.10.1. 2681.
ReactomeiR-HSA-1257604. PIP3 activates AKT signaling.
R-HSA-186763. Downstream signal transduction.
R-HSA-186797. Signaling by PDGF.
R-HSA-2219530. Constitutive Signaling by Aberrant PI3K in Cancer.
R-HSA-5673001. RAF/MAP kinase cascade.
R-HSA-6811558. PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling.
SignaLinkiP16234.
SIGNORiP16234.

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
CD140a antigen
Platelet-derived growth factor alpha receptor
Platelet-derived growth factor receptor 2
Short name:
PDGFR-2
CD_antigen: CD140a
Gene namesi
Name:PDGFRA
Synonyms:PDGFR2, RHEPDGFRA
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 4

Organism-specific databases

HGNCiHGNC:8803. PDGFRA.

Subcellular locationi

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini24 – 528ExtracellularSequence analysisAdd BLAST505
Transmembranei529 – 549HelicalSequence analysisAdd BLAST21
Topological domaini550 – 1089CytoplasmicSequence analysisAdd BLAST540

GO - Cellular componenti

  • cytoplasm Source: UniProtKB
  • integral component of plasma membrane Source: BHF-UCL
  • intrinsic component of plasma membrane Source: UniProtKB
  • membrane Source: UniProtKB
  • nucleus Source: UniProtKB
  • plasma membrane Source: Reactome
  • protein complex Source: MGI
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Membrane

Pathology & Biotechi

Involvement in diseasei

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.

Gastrointestinal stromal tumor (GIST)2 Publications
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).1 Publication
Disease descriptionCommon 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.
See also OMIM:606764
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_066462561V → D in a GIST sample; constitutively activated kinase. 2 PublicationsCorresponds to variant rs121908586dbSNPEnsembl.1
Natural variantiVAR_066466659N → K in GIST sample; constitutively activated kinase. 1 Publication1
Natural variantiVAR_066470842 – 845Missing in a GIST sample; constitutively activated kinase. 2 Publications4
Natural variantiVAR_066471842D → V in a GIST sample; imatinib resistant, constitutively activated kinase. 3 PublicationsCorresponds to variant rs121908585dbSNPEnsembl.1
Natural variantiVAR_066472842D → Y in a GIST sample; imatinib sensitive, constitutively activated kinase. 1 PublicationCorresponds to variant rs121913265dbSNPEnsembl.1
Natural variantiVAR_066473845 – 848Missing in a GIST sample; constitutively activated kinase. 2 Publications4
Natural variantiVAR_066474849Y → C in GIST. 1 Publication1

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi572Y → F: Abolishes interaction with SRC-family members and impairs internalization of the activated receptor; when associated with F-574. 2 Publications1
Mutagenesisi574Y → F: Abolishes interaction with SRC-family members and impairs internalization of the activated receptor; when associated with F-572. 2 Publications1
Mutagenesisi720Y → F: Strongly reduced interaction with PTPN11 and GRB2. 1 Publication1
Mutagenesisi731Y → F: No effect on autophosphorylation and phosphorylation of PLCG1. Abolishes activation of phosphatidylinositol 3-kinase. 1 Publication1
Mutagenesisi742Y → F: No effect on autophosphorylation and phosphorylation of PLCG1. Abolishes activation of phosphatidylinositol 3-kinase. 1 Publication1
Mutagenesisi762Y → F: Abolishes interaction with CRK. 1 Publication1

Keywords - Diseasei

Proto-oncogene

Organism-specific databases

DisGeNETi5156.
MalaCardsiPDGFRA.
MIMi606764. phenotype.
607685. phenotype.
OpenTargetsiENSG00000134853.
Orphaneti44890. Gastrointestinal stromal tumor.
168947. Myeloid neoplasm associated with PDGFRA rearrangement.
99860. Precursor B-cell acute lymphoblastic leukemia.
314950. Primary hypereosinophilic syndrome.
PharmGKBiPA33147.

Chemistry databases

ChEMBLiCHEMBL2007.
DrugBankiDB00102. Becaplermin.
DB00619. Imatinib.
DB06589. Pazopanib.
DB08901. Ponatinib.
DB08896. Regorafenib.
DB01268. Sunitinib.
GuidetoPHARMACOLOGYi1803.

Polymorphism and mutation databases

BioMutaiPDGFRA.
DMDMi129892.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 23Add BLAST23
ChainiPRO_000001676024 – 1089Platelet-derived growth factor receptor alphaAdd BLAST1066

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi42N-linked (GlcNAc...)Sequence analysis1
Disulfide bondi49 ↔ 100PROSITE-ProRule annotation
Glycosylationi76N-linked (GlcNAc...)Sequence analysis1
Glycosylationi103N-linked (GlcNAc...)Sequence analysis1
Disulfide bondi150 ↔ 189PROSITE-ProRule annotation
Glycosylationi179N-linked (GlcNAc...)Sequence analysis1
Disulfide bondi235 ↔ 290PROSITE-ProRule annotation
Glycosylationi353N-linked (GlcNAc...)Sequence analysis1
Glycosylationi359N-linked (GlcNAc...)Sequence analysis1
Disulfide bondi435 ↔ 501PROSITE-ProRule annotation
Glycosylationi458N-linked (GlcNAc...)Sequence analysis1
Glycosylationi468N-linked (GlcNAc...)Sequence analysis1
Modified residuei572Phosphotyrosine; by autocatalysis1 Publication1
Modified residuei574Phosphotyrosine; by autocatalysis1 Publication1
Modified residuei720Phosphotyrosine; by autocatalysis2 Publications1
Modified residuei731Phosphotyrosine; by autocatalysis1 Publication1
Modified residuei742Phosphotyrosine; by autocatalysis1 Publication1
Modified residuei754Phosphotyrosine; by autocatalysis1 Publication1
Modified residuei762Phosphotyrosine; by autocatalysis1 Publication1
Modified residuei768Phosphotyrosine; by autocatalysis1 Publication1
Modified residuei849Phosphotyrosine; by autocatalysisBy similarity1
Modified residuei988Phosphotyrosine; by autocatalysis1 Publication1
Modified residuei1018Phosphotyrosine; by autocatalysis1 Publication1

Post-translational modificationi

N-glycosylated.
Ubiquitinated, leading to its degradation.1 Publication
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 PLCG1.6 Publications

Keywords - PTMi

Disulfide bond, Glycoprotein, Phosphoprotein, Ubl conjugation

Proteomic databases

MaxQBiP16234.
PaxDbiP16234.
PeptideAtlasiP16234.
PRIDEiP16234.

PTM databases

iPTMnetiP16234.
PhosphoSitePlusiP16234.

Expressioni

Tissue specificityi

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.3 Publications

Gene expression databases

BgeeiENSG00000134853.
CleanExiHS_PDGFRA.
ExpressionAtlasiP16234. baseline and differential.
GenevisibleiP16234. HS.

Organism-specific databases

HPAiCAB018143.

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) (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.By similarity15 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
CCDC155Q8N6L03EBI-2861522,EBI-749265
CRKP461084EBI-2861522,EBI-886
CRKLP461093EBI-2861522,EBI-910
EGFRP005333EBI-2861522,EBI-297353
PDGFAP040856EBI-2861522,EBI-2881386
PDGFBP0112711EBI-2861522,EBI-1554925
PDGFCQ9NRA12EBI-2861522,EBI-8833587

GO - Molecular functioni

  • platelet-derived growth factor binding Source: UniProtKB
  • platelet-derived growth factor receptor binding Source: BHF-UCL
  • protein homodimerization activity Source: BHF-UCL
  • vascular endothelial growth factor binding Source: BHF-UCL

Protein-protein interaction databases

BioGridi111182. 49 interactors.
DIPiDIP-5736N.
IntActiP16234. 37 interactors.
MINTiMINT-4529366.
STRINGi9606.ENSP00000257290.

Chemistry databases

BindingDBiP16234.

Structurei

Secondary structure

11089
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi560 – 565Combined sources6
Beta strandi572 – 574Combined sources3
Helixi577 – 579Combined sources3
Helixi584 – 586Combined sources3
Helixi590 – 592Combined sources3
Beta strandi593 – 601Combined sources9
Beta strandi603 – 615Combined sources13
Beta strandi620 – 629Combined sources10
Helixi635 – 651Combined sources17
Beta strandi660 – 664Combined sources5
Beta strandi666 – 669Combined sources4
Beta strandi671 – 675Combined sources5
Helixi682 – 688Combined sources7
Helixi774 – 776Combined sources3
Helixi778 – 781Combined sources4
Helixi792 – 811Combined sources20
Helixi821 – 823Combined sources3
Beta strandi824 – 827Combined sources4
Turni828 – 830Combined sources3
Beta strandi831 – 834Combined sources4
Helixi838 – 840Combined sources3
Helixi843 – 845Combined sources3
Beta strandi850 – 852Combined sources3
Beta strandi855 – 857Combined sources3
Helixi859 – 861Combined sources3
Helixi864 – 869Combined sources6
Helixi874 – 889Combined sources16
Helixi903 – 910Combined sources8
Helixi923 – 932Combined sources10
Helixi937 – 939Combined sources3
Helixi943 – 951Combined sources9
Helixi956 – 971Combined sources16

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1GQ5X-ray2.20
5K5XX-ray2.17A550-973[»]
ProteinModelPortaliP16234.
SMRiP16234.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP16234.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini24 – 113Ig-like C2-type 1Add BLAST90
Domaini117 – 201Ig-like C2-type 2Add BLAST85
Domaini202 – 306Ig-like C2-type 3Add BLAST105
Domaini319 – 410Ig-like C2-type 4Add BLAST92
Domaini414 – 517Ig-like C2-type 5Add BLAST104
Domaini593 – 954Protein kinasePROSITE-ProRule annotationAdd BLAST362

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi1041 – 1087Ser-richAdd BLAST47

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.
GeneTreeiENSGT00760000118923.
HOGENOMiHOG000112009.
HOVERGENiHBG004335.
InParanoidiP16234.
KOiK04363.
OMAiDSAIIPC.
OrthoDBiEOG091G01TL.
PhylomeDBiP16234.
TreeFamiTF325768.

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. 2 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]

Sequences (3)i

Sequence statusi: Complete.

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

This entry describes 3 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: P16234-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MGTSHPAFLV LGCLLTGLSL ILCQLSLPSI LPNENEKVVQ LNSSFSLRCF
60 70 80 90 100
GESEVSWQYP MSEEESSDVE IRNEENNSGL FVTVLEVSSA SAAHTGLYTC
110 120 130 140 150
YYNHTQTEEN ELEGRHIYIY VPDPDVAFVP LGMTDYLVIV EDDDSAIIPC
160 170 180 190 200
RTTDPETPVT LHNSEGVVPA SYDSRQGFNG TFTVGPYICE ATVKGKKFQT
210 220 230 240 250
IPFNVYALKA TSELDLEMEA LKTVYKSGET IVVTCAVFNN EVVDLQWTYP
260 270 280 290 300
GEVKGKGITM LEEIKVPSIK LVYTLTVPEA TVKDSGDYEC AARQATREVK
310 320 330 340 350
EMKKVTISVH EKGFIEIKPT FSQLEAVNLH EVKHFVVEVR AYPPPRISWL
360 370 380 390 400
KNNLTLIENL TEITTDVEKI QEIRYRSKLK LIRAKEEDSG HYTIVAQNED
410 420 430 440 450
AVKSYTFELL TQVPSSILDL VDDHHGSTGG QTVRCTAEGT PLPDIEWMIC
460 470 480 490 500
KDIKKCNNET SWTILANNVS NIITEIHSRD RSTVEGRVTF AKVEETIAVR
510 520 530 540 550
CLAKNLLGAE NRELKLVAPT LRSELTVAAA VLVLLVIVII SLIVLVVIWK
560 570 580 590 600
QKPRYEIRWR VIESISPDGH EYIYVDPMQL PYDSRWEFPR DGLVLGRVLG
610 620 630 640 650
SGAFGKVVEG TAYGLSRSQP VMKVAVKMLK PTARSSEKQA LMSELKIMTH
660 670 680 690 700
LGPHLNIVNL LGACTKSGPI YIITEYCFYG DLVNYLHKNR DSFLSHHPEK
710 720 730 740 750
PKKELDIFGL NPADESTRSY VILSFENNGD YMDMKQADTT QYVPMLERKE
760 770 780 790 800
VSKYSDIQRS LYDRPASYKK KSMLDSEVKN LLSDDNSEGL TLLDLLSFTY
810 820 830 840 850
QVARGMEFLA SKNCVHRDLA ARNVLLAQGK IVKICDFGLA RDIMHDSNYV
860 870 880 890 900
SKGSTFLPVK WMAPESIFDN LYTTLSDVWS YGILLWEIFS LGGTPYPGMM
910 920 930 940 950
VDSTFYNKIK SGYRMAKPDH ATSEVYEIMV KCWNSEPEKR PSFYHLSEIV
960 970 980 990 1000
ENLLPGQYKK SYEKIHLDFL KSDHPAVARM RVDSDNAYIG VTYKNEEDKL
1010 1020 1030 1040 1050
KDWEGGLDEQ RLSADSGYII PLPDIDPVPE EEDLGKRNRH SSQTSEESAI
1060 1070 1080
ETGSSSSTFI KREDETIEDI DMMDDIGIDS SDLVEDSFL
Length:1,089
Mass (Da):122,670
Last modified:April 1, 1990 - v1
Checksum:i5E3FB9940ACD1BE8
GO
Isoform 2 (identifier: P16234-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     210-218: ATSELDLEM → GTCIISFLL
     219-1089: Missing.

Note: No experimental confirmation available.
Show »
Length:218
Mass (Da):24,023
Checksum:iE8144A73DFD069BF
GO
Isoform 3 (identifier: P16234-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     720-743: YVILSFENNGDYMDMKQADTTQYV → SGQGCLSSGTLQELSVDLQARGPC
     744-1089: Missing.

Show »
Length:743
Mass (Da):82,809
Checksum:i2456B1766606C60F
GO

Sequence cautioni

The sequence AAP69563 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.Curated

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_04203279G → D.1 PublicationCorresponds to variant rs36035373dbSNPEnsembl.1
Natural variantiVAR_042033426G → D.1 PublicationCorresponds to variant rs55865821dbSNPEnsembl.1
Natural variantiVAR_034378478S → P.3 PublicationsCorresponds to variant rs35597368dbSNPEnsembl.1
Natural variantiVAR_066460481R → G in a hypereosinophilic syndrome sample; does not lead to constitutive kinase activation. 1 Publication1
Natural variantiVAR_066461507L → P in a hypereosinophilic syndrome sample; does not lead to constitutive kinase activation. 1 Publication1
Natural variantiVAR_066462561V → D in a GIST sample; constitutively activated kinase. 2 PublicationsCorresponds to variant rs121908586dbSNPEnsembl.1
Natural variantiVAR_066463562I → M in a hypereosinophilic syndrome sample; does not lead to constitutive kinase activation. 1 Publication1
Natural variantiVAR_066464570H → R in a hypereosinophilic syndrome sample; does not lead to constitutive kinase activation. 1 Publication1
Natural variantiVAR_066465650H → Q in a hypereosinophilic syndrome sample; constitutively activated kinase. 1 Publication1
Natural variantiVAR_066466659N → K in GIST sample; constitutively activated kinase. 1 Publication1
Natural variantiVAR_066467659N → S in a hypereosinophilic syndrome sample; constitutively activated kinase. 1 Publication1
Natural variantiVAR_066468705L → P in a hypereosinophilic syndrome sample; does not lead to constitutive kinase activation. 1 Publication1
Natural variantiVAR_066469748R → G in a hypereosinophilic syndrome sample; constitutively activated kinase. 1 Publication1
Natural variantiVAR_042034764R → C.1 PublicationCorresponds to variant rs34392012dbSNPEnsembl.1
Natural variantiVAR_042035829G → R in a glioblastoma multiforme sample; somatic mutation. 1 Publication1
Natural variantiVAR_066470842 – 845Missing in a GIST sample; constitutively activated kinase. 2 Publications4
Natural variantiVAR_066471842D → V in a GIST sample; imatinib resistant, constitutively activated kinase. 3 PublicationsCorresponds to variant rs121908585dbSNPEnsembl.1
Natural variantiVAR_066472842D → Y in a GIST sample; imatinib sensitive, constitutively activated kinase. 1 PublicationCorresponds to variant rs121913265dbSNPEnsembl.1
Natural variantiVAR_066473845 – 848Missing in a GIST sample; constitutively activated kinase. 2 Publications4
Natural variantiVAR_066474849Y → C in GIST. 1 Publication1
Natural variantiVAR_066475849Y → S in a hypereosinophilic syndrome sample; constitutively activated kinase. 1 Publication1
Natural variantiVAR_042036996E → K in a metastatic melanoma sample; somatic mutation. 1 PublicationCorresponds to variant rs779173667dbSNPEnsembl.1
Natural variantiVAR_0420371071D → N in a lung neuroendocrine carcinoma sample; somatic mutation. 1 PublicationCorresponds to variant rs376544204dbSNPEnsembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_007833210 – 218ATSELDLEM → GTCIISFLL in isoform 2. 1 Publication9
Alternative sequenceiVSP_007834219 – 1089Missing in isoform 2. 1 PublicationAdd BLAST871
Alternative sequenceiVSP_042015720 – 743YVILS…TTQYV → SGQGCLSSGTLQELSVDLQA RGPC in isoform 3. 1 PublicationAdd BLAST24
Alternative sequenceiVSP_042016744 – 1089Missing in isoform 3. 1 PublicationAdd BLAST346

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M22734 mRNA. Translation: AAA60048.1.
M21574 mRNA. Translation: AAA96715.1.
D50017 Genomic DNA. Translation: BAA08742.1.
AK316578 mRNA. Translation: BAG38166.1.
AC098587 Genomic DNA. No translation available.
AC138779 Genomic DNA. No translation available.
BC015186 mRNA. Translation: AAH15186.1.
BC063414 mRNA. Translation: AAH63414.1.
AY229892 mRNA. Translation: AAP69563.1. Different initiation.
CCDSiCCDS3495.1. [P16234-1]
PIRiA40162. PFHUGA.
RefSeqiNP_006197.1. NM_006206.4. [P16234-1]
XP_005265800.1. XM_005265743.1. [P16234-1]
XP_011532687.1. XM_011534385.2. [P16234-1]
UniGeneiHs.74615.

Genome annotation databases

EnsembliENST00000257290; ENSP00000257290; ENSG00000134853. [P16234-1]
ENST00000508170; ENSP00000425648; ENSG00000134853. [P16234-2]
ENST00000509490; ENSP00000424218; ENSG00000134853. [P16234-3]
GeneIDi5156.
KEGGihsa:5156.
UCSCiuc003hal.4. human. [P16234-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M22734 mRNA. Translation: AAA60048.1.
M21574 mRNA. Translation: AAA96715.1.
D50017 Genomic DNA. Translation: BAA08742.1.
AK316578 mRNA. Translation: BAG38166.1.
AC098587 Genomic DNA. No translation available.
AC138779 Genomic DNA. No translation available.
BC015186 mRNA. Translation: AAH15186.1.
BC063414 mRNA. Translation: AAH63414.1.
AY229892 mRNA. Translation: AAP69563.1. Different initiation.
CCDSiCCDS3495.1. [P16234-1]
PIRiA40162. PFHUGA.
RefSeqiNP_006197.1. NM_006206.4. [P16234-1]
XP_005265800.1. XM_005265743.1. [P16234-1]
XP_011532687.1. XM_011534385.2. [P16234-1]
UniGeneiHs.74615.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1GQ5X-ray2.20
5K5XX-ray2.17A550-973[»]
ProteinModelPortaliP16234.
SMRiP16234.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi111182. 49 interactors.
DIPiDIP-5736N.
IntActiP16234. 37 interactors.
MINTiMINT-4529366.
STRINGi9606.ENSP00000257290.

Chemistry databases

BindingDBiP16234.
ChEMBLiCHEMBL2007.
DrugBankiDB00102. Becaplermin.
DB00619. Imatinib.
DB06589. Pazopanib.
DB08901. Ponatinib.
DB08896. Regorafenib.
DB01268. Sunitinib.
GuidetoPHARMACOLOGYi1803.

PTM databases

iPTMnetiP16234.
PhosphoSitePlusiP16234.

Polymorphism and mutation databases

BioMutaiPDGFRA.
DMDMi129892.

Proteomic databases

MaxQBiP16234.
PaxDbiP16234.
PeptideAtlasiP16234.
PRIDEiP16234.

Protocols and materials databases

DNASUi5156.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000257290; ENSP00000257290; ENSG00000134853. [P16234-1]
ENST00000508170; ENSP00000425648; ENSG00000134853. [P16234-2]
ENST00000509490; ENSP00000424218; ENSG00000134853. [P16234-3]
GeneIDi5156.
KEGGihsa:5156.
UCSCiuc003hal.4. human. [P16234-1]

Organism-specific databases

CTDi5156.
DisGeNETi5156.
GeneCardsiPDGFRA.
HGNCiHGNC:8803. PDGFRA.
HPAiCAB018143.
MalaCardsiPDGFRA.
MIMi173490. gene.
606764. phenotype.
607685. phenotype.
neXtProtiNX_P16234.
OpenTargetsiENSG00000134853.
Orphaneti44890. Gastrointestinal stromal tumor.
168947. Myeloid neoplasm associated with PDGFRA rearrangement.
99860. Precursor B-cell acute lymphoblastic leukemia.
314950. Primary hypereosinophilic syndrome.
PharmGKBiPA33147.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG0200. Eukaryota.
COG0515. LUCA.
GeneTreeiENSGT00760000118923.
HOGENOMiHOG000112009.
HOVERGENiHBG004335.
InParanoidiP16234.
KOiK04363.
OMAiDSAIIPC.
OrthoDBiEOG091G01TL.
PhylomeDBiP16234.
TreeFamiTF325768.

Enzyme and pathway databases

BioCyciZFISH:HS05923-MONOMER.
BRENDAi2.7.10.1. 2681.
ReactomeiR-HSA-1257604. PIP3 activates AKT signaling.
R-HSA-186763. Downstream signal transduction.
R-HSA-186797. Signaling by PDGF.
R-HSA-2219530. Constitutive Signaling by Aberrant PI3K in Cancer.
R-HSA-5673001. RAF/MAP kinase cascade.
R-HSA-6811558. PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling.
SignaLinkiP16234.
SIGNORiP16234.

Miscellaneous databases

ChiTaRSiPDGFRA. human.
EvolutionaryTraceiP16234.
GeneWikiiPDGFRA.
GenomeRNAii5156.
PROiP16234.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000134853.
CleanExiHS_PDGFRA.
ExpressionAtlasiP16234. baseline and differential.
GenevisibleiP16234. HS.

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. 2 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_HUMAN
AccessioniPrimary (citable) accession number: P16234
Secondary accession number(s): B2RE69
, E9PBH0, Q6P4H5, Q96KZ7, Q9UD28
Entry historyi
Integrated into UniProtKB/Swiss-Prot: April 1, 1990
Last sequence update: April 1, 1990
Last modified: November 30, 2016
This is version 192 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human cell differentiation molecules
    CD nomenclature of surface proteins of human leucocytes and list of entries
  2. Human chromosome 4
    Human chromosome 4: entries, gene names and cross-references to MIM
  3. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  4. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  5. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  6. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  7. Human and mouse protein kinases
    Human and mouse protein kinases: classification and index
  8. 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.