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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)LengthDescriptionGraphical viewFeature identifierActions
Sitei578 – 5792Breakpoint for interstitial deletion to form the FIP1L1-PDGFRA fusion protein
Binding sitei627 – 6271ATPPROSITE-ProRule annotation
Active sitei818 – 8181Proton acceptorPROSITE-ProRule annotation

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Nucleotide bindingi599 – 6079ATPPROSITE-ProRule annotation

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

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)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini24 – 528505ExtracellularSequence analysisAdd
BLAST
Transmembranei529 – 54921HelicalSequence analysisAdd
BLAST
Topological domaini550 – 1089540CytoplasmicSequence analysisAdd
BLAST

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)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti561 – 5611V → D in a GIST sample; constitutively activated kinase. 2 Publications
Corresponds to variant rs121908586 [ dbSNP | Ensembl ].
VAR_066462
Natural varianti659 – 6591N → K in GIST sample; constitutively activated kinase. 1 Publication
VAR_066466
Natural varianti842 – 8454Missing in a GIST sample; constitutively activated kinase. 2 Publications
VAR_066470
Natural varianti842 – 8421D → V in a GIST sample; imatinib resistant, constitutively activated kinase. 3 Publications
Corresponds to variant rs121908585 [ dbSNP | Ensembl ].
VAR_066471
Natural varianti842 – 8421D → Y in a GIST sample; imatinib sensitive, constitutively activated kinase. 1 Publication
VAR_066472
Natural varianti845 – 8484Missing in a GIST sample; constitutively activated kinase. 2 Publications
VAR_066473
Natural varianti849 – 8491Y → C in GIST. 1 Publication
VAR_066474

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi572 – 5721Y → F: Abolishes interaction with SRC-family members and impairs internalization of the activated receptor; when associated with F-574. 2 Publications
Mutagenesisi574 – 5741Y → F: Abolishes interaction with SRC-family members and impairs internalization of the activated receptor; when associated with F-572. 2 Publications
Mutagenesisi720 – 7201Y → F: Strongly reduced interaction with PTPN11 and GRB2. 1 Publication
Mutagenesisi731 – 7311Y → F: No effect on autophosphorylation and phosphorylation of PLCG1. Abolishes activation of phosphatidylinositol 3-kinase. 1 Publication
Mutagenesisi742 – 7421Y → F: No effect on autophosphorylation and phosphorylation of PLCG1. Abolishes activation of phosphatidylinositol 3-kinase. 1 Publication
Mutagenesisi762 – 7621Y → F: Abolishes interaction with CRK. 1 Publication

Keywords - Diseasei

Proto-oncogene

Organism-specific databases

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

Chemistry

ChEMBLiCHEMBL2095189.
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)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 2323Add
BLAST
Chaini24 – 10891066Platelet-derived growth factor receptor alphaPRO_0000016760Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Glycosylationi42 – 421N-linked (GlcNAc...)Sequence analysis
Disulfide bondi49 ↔ 100PROSITE-ProRule annotation
Glycosylationi76 – 761N-linked (GlcNAc...)Sequence analysis
Glycosylationi103 – 1031N-linked (GlcNAc...)Sequence analysis
Disulfide bondi150 ↔ 189PROSITE-ProRule annotation
Glycosylationi179 – 1791N-linked (GlcNAc...)Sequence analysis
Disulfide bondi235 ↔ 290PROSITE-ProRule annotation
Glycosylationi353 – 3531N-linked (GlcNAc...)Sequence analysis
Glycosylationi359 – 3591N-linked (GlcNAc...)Sequence analysis
Disulfide bondi435 ↔ 501PROSITE-ProRule annotation
Glycosylationi458 – 4581N-linked (GlcNAc...)Sequence analysis
Glycosylationi468 – 4681N-linked (GlcNAc...)Sequence analysis
Modified residuei572 – 5721Phosphotyrosine; by autocatalysis1 Publication
Modified residuei574 – 5741Phosphotyrosine; by autocatalysis1 Publication
Modified residuei720 – 7201Phosphotyrosine; by autocatalysis2 Publications
Modified residuei731 – 7311Phosphotyrosine; by autocatalysis1 Publication
Modified residuei742 – 7421Phosphotyrosine; by autocatalysis1 Publication
Modified residuei754 – 7541Phosphotyrosine; by autocatalysis1 Publication
Modified residuei762 – 7621Phosphotyrosine; by autocatalysis1 Publication
Modified residuei768 – 7681Phosphotyrosine; by autocatalysis1 Publication
Modified residuei849 – 8491Phosphotyrosine; by autocatalysisBy similarity
Modified residuei988 – 9881Phosphotyrosine; by autocatalysis1 Publication
Modified residuei1018 – 10181Phosphotyrosine; by autocatalysis1 Publication

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.
PhosphoSiteiP16234.

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 interactions.
DIPiDIP-5736N.
IntActiP16234. 37 interactions.
MINTiMINT-4529366.
STRINGi9606.ENSP00000257290.

Chemistry

BindingDBiP16234.

Structurei

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
1GQ5X-ray2.20
ProteinModelPortaliP16234.
SMRiP16234. Positions 26-509, 551-997.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP16234.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini24 – 11390Ig-like C2-type 1Add
BLAST
Domaini117 – 20185Ig-like C2-type 2Add
BLAST
Domaini202 – 306105Ig-like C2-type 3Add
BLAST
Domaini319 – 41092Ig-like C2-type 4Add
BLAST
Domaini414 – 517104Ig-like C2-type 5Add
BLAST
Domaini593 – 954362Protein kinasePROSITE-ProRule annotationAdd
BLAST

Compositional bias

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Compositional biasi1041 – 108747Ser-richAdd
BLAST

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)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti79 – 791G → D.1 Publication
Corresponds to variant rs36035373 [ dbSNP | Ensembl ].
VAR_042032
Natural varianti426 – 4261G → D.1 Publication
Corresponds to variant rs55865821 [ dbSNP | Ensembl ].
VAR_042033
Natural varianti478 – 4781S → P.3 Publications
Corresponds to variant rs35597368 [ dbSNP | Ensembl ].
VAR_034378
Natural varianti481 – 4811R → G in a hypereosinophilic syndrome sample; does not lead to constitutive kinase activation. 1 Publication
VAR_066460
Natural varianti507 – 5071L → P in a hypereosinophilic syndrome sample; does not lead to constitutive kinase activation. 1 Publication
VAR_066461
Natural varianti561 – 5611V → D in a GIST sample; constitutively activated kinase. 2 Publications
Corresponds to variant rs121908586 [ dbSNP | Ensembl ].
VAR_066462
Natural varianti562 – 5621I → M in a hypereosinophilic syndrome sample; does not lead to constitutive kinase activation. 1 Publication
VAR_066463
Natural varianti570 – 5701H → R in a hypereosinophilic syndrome sample; does not lead to constitutive kinase activation. 1 Publication
VAR_066464
Natural varianti650 – 6501H → Q in a hypereosinophilic syndrome sample; constitutively activated kinase. 1 Publication
VAR_066465
Natural varianti659 – 6591N → K in GIST sample; constitutively activated kinase. 1 Publication
VAR_066466
Natural varianti659 – 6591N → S in a hypereosinophilic syndrome sample; constitutively activated kinase. 1 Publication
VAR_066467
Natural varianti705 – 7051L → P in a hypereosinophilic syndrome sample; does not lead to constitutive kinase activation. 1 Publication
VAR_066468
Natural varianti748 – 7481R → G in a hypereosinophilic syndrome sample; constitutively activated kinase. 1 Publication
VAR_066469
Natural varianti764 – 7641R → C.1 Publication
Corresponds to variant rs34392012 [ dbSNP | Ensembl ].
VAR_042034
Natural varianti829 – 8291G → R in a glioblastoma multiforme sample; somatic mutation. 1 Publication
VAR_042035
Natural varianti842 – 8454Missing in a GIST sample; constitutively activated kinase. 2 Publications
VAR_066470
Natural varianti842 – 8421D → V in a GIST sample; imatinib resistant, constitutively activated kinase. 3 Publications
Corresponds to variant rs121908585 [ dbSNP | Ensembl ].
VAR_066471
Natural varianti842 – 8421D → Y in a GIST sample; imatinib sensitive, constitutively activated kinase. 1 Publication
VAR_066472
Natural varianti845 – 8484Missing in a GIST sample; constitutively activated kinase. 2 Publications
VAR_066473
Natural varianti849 – 8491Y → C in GIST. 1 Publication
VAR_066474
Natural varianti849 – 8491Y → S in a hypereosinophilic syndrome sample; constitutively activated kinase. 1 Publication
VAR_066475
Natural varianti996 – 9961E → K in a metastatic melanoma sample; somatic mutation. 1 Publication
Corresponds to variant rs779173667 [ dbSNP | Ensembl ].
VAR_042036
Natural varianti1071 – 10711D → N in a lung neuroendocrine carcinoma sample; somatic mutation. 1 Publication
Corresponds to variant rs376544204 [ dbSNP | Ensembl ].
VAR_042037

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei210 – 2189ATSELDLEM → GTCIISFLL in isoform 2. 1 PublicationVSP_007833
Alternative sequencei219 – 1089871Missing in isoform 2. 1 PublicationVSP_007834Add
BLAST
Alternative sequencei720 – 74324YVILS…TTQYV → SGQGCLSSGTLQELSVDLQA RGPC in isoform 3. 1 PublicationVSP_042015Add
BLAST
Alternative sequencei744 – 1089346Missing in isoform 3. 1 PublicationVSP_042016Add
BLAST

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
EntryMethodResolution (Å)ChainPositionsPDBsum
1GQ5X-ray2.20
ProteinModelPortaliP16234.
SMRiP16234. Positions 26-509, 551-997.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

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

Chemistry

BindingDBiP16234.
ChEMBLiCHEMBL2095189.
DrugBankiDB00102. Becaplermin.
DB00619. Imatinib.
DB06589. Pazopanib.
DB08901. Ponatinib.
DB08896. Regorafenib.
DB01268. Sunitinib.
GuidetoPHARMACOLOGYi1803.

PTM databases

iPTMnetiP16234.
PhosphoSiteiP16234.

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.
GeneCardsiPDGFRA.
HGNCiHGNC:8803. PDGFRA.
HPAiCAB018143.
MalaCardsiPDGFRA.
MIMi173490. gene.
606764. phenotype.
607685. phenotype.
neXtProtiNX_P16234.
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

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: September 7, 2016
This is version 189 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.