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UniProtKB/Swiss-Prot entry P09619


[Entry info] [Name and origin] [References] [Comments] [Cross-references] [Keywords] [Features] [Sequence] [Tools]

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Entry information
Entry name PGFRB_HUMAN
Primary accession number P09619
Secondary accession number Q8N5L4
Integrated into Swiss-Prot on July 1, 1989
Sequence was last modified on July 1, 1989 (Sequence version 1)
Annotations were last modified on    December 16, 2008 (Entry version 117)
Name and origin of the protein
Protein name Beta-type platelet-derived growth factor receptor [Precursor]
Synonyms EC 2.7.10.1
PDGF-R-beta
CD140 antigen-like family member B
CD140b antigen
Gene name
Name: PDGFRB
From
Homo sapiens (Human) [TaxID: 9606] 
Taxonomy Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.
Protein existence 1: Evidence at protein level;
References
[1]
NUCLEOTIDE SEQUENCE [MRNA].
PubMed=2835772 [NCBI, ExPASy, EBI, Israel, Japan]
Gronwald R.G.K., Grant F.J., Haldeman B.A., Hart C.E., O'Hara P.J., Hagen F.S., Ross R., Bowen-Pope D.F., Murray M.J.;
"Cloning and expression of a cDNA coding for the human platelet-derived growth factor receptor: evidence for more than one receptor class.";
Proc. Natl. Acad. Sci. U.S.A. 85:3435-3439(1988).
[2]
NUCLEOTIDE SEQUENCE [MRNA].
PubMed=2850496 [NCBI, ExPASy, EBI, Israel, Japan]
Claesson-Welsh L., Eriksson A., Moren A., Severinsson L., Ek B., Oestman A., Betsholtz C., Heldin C.-H.;
"cDNA cloning and expression of a human platelet-derived growth factor (PDGF) receptor specific for B-chain-containing PDGF molecules.";
Mol. Cell. Biol. 8:3476-3486(1988).
[3]
NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT PHE-180.
TISSUE=Brain;
DOI=10.1101/gr.2596504; PubMed=15489334 [NCBI, ExPASy, EBI, Israel, Japan]
The MGC Project Team;
"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).";
Genome Res. 14:2121-2127(2004).
[4]
NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 548-569.
DOI=10.1038/sj.onc.1201267; PubMed=9285559 [NCBI, ExPASy, EBI, Israel, Japan]
Chi K.D., McPhee R.A., Wagner A.S., Dietz J.J., Pantazis P., Goustin A.S.;
"Integration of proviral DNA into the PDGF beta-receptor gene in HTLV-I-infected T-cells results in a novel tyrosine kinase product with transforming activity.";
Oncogene 15:1051-1057(1997).
[5]
NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1046-1106.
DOI=10.1016/0092-8674(88)90224-3; PubMed=2846185 [NCBI, ExPASy, EBI, Israel, Japan]
Roberts W.M., Look A.T., Roussel M.F., Sherr C.J.;
"Tandem linkage of human CSF-1 receptor (c-fms) and PDGF receptor genes.";
Cell 55:655-661(1988).
[6]
PROTEIN SEQUENCE OF 33-47.
DOI=10.1110/ps.04682504; PubMed=15340161 [NCBI, ExPASy, EBI, Israel, Japan]
Zhang Z., Henzel W.J.;
"Signal peptide prediction based on analysis of experimentally verified cleavage sites.";
Protein Sci. 13:2819-2824(2004).
[7]
PHOSPHORYLATION AT TYR-751 AND TYR-857.
DOI=10.1016/0092-8674(89)90510-2; PubMed=2550144 [NCBI, ExPASy, EBI, Israel, Japan]
Kazlauskas A., Cooper J.A.;
"Autophosphorylation of the PDGF receptor in the kinase insert region regulates interactions with cell proteins.";
Cell 58:1121-1133(1989).
[8]
INTERACTION WITH SHB.
PubMed=8302579 [NCBI, ExPASy, EBI, Israel, Japan]
Welsh M., Mares J., Karlsson T., Lavergne C., Breant B., Claesson-Welsh L.;
"Shb is a ubiquitously expressed Src homology 2 protein.";
Oncogene 9:19-27(1994).
[9]
CHROMOSOMAL TRANSLOCATION WITH TRIP11.
PubMed=9373237 [NCBI, ExPASy, EBI, Israel, Japan]
Abe A., Emi N., Tanimoto M., Terasaki H., Marunouchi T., Saito H.;
"Fusion of the platelet-derived growth factor receptor beta to a novel gene CEV14 in acute myelogenous leukemia after clonal evolution.";
Blood 90:4271-4277(1997).
[10]
INTERACTION WITH APS.
DOI=10.1038/sj.onc.1202326; PubMed=9989826 [NCBI, ExPASy, EBI, Israel, Japan]
Yokouchi M., Wakioka T., Sakamoto H., Yasukawa H., Ohtsuka S., Sasaki A., Ohtsubo M., Valius M., Inoue A., Komiya S., Yoshimura A.;
"APS, an adaptor protein containing PH and SH2 domains, is associated with the PDGF receptor and c-Cbl and inhibits PDGF-induced mitogenesis.";
Oncogene 18:759-767(1999).
[11]
INTERACTION WITH PIK3C2B.
DOI=10.1128/MCB.20.11.3817-3830.2000; PubMed=10805725 [NCBI, ExPASy, EBI, Israel, Japan]
Arcaro A., Zvelebil M.J., Wallasch C., Ullrich A., Waterfield M.D., Domin J.;
"Class II phosphoinositide 3-kinases are downstream targets of activated polypeptide growth factor receptors.";
Mol. Cell. Biol. 20:3817-3830(2000).
[12]
FUNCTION AS A RECEPTOR FOR PDGFD.
DOI=10.1038/35074588; PubMed=11331881 [NCBI, ExPASy, EBI, Israel, Japan]
Bergsten E., Uutela M., Li X., Pietras K., Oestman A., Heldin C.-H., Alitalo K., Eriksson U.;
"PDGF-D is a specific, protease-activated ligand for the PDGF beta-receptor.";
Nat. Cell Biol. 3:512-516(2001).
[13]
CHROMOSOMAL TRANSLOCATION WITH ETV6.
DOI=10.1056/NEJMoa020150; PubMed=12181402 [NCBI, ExPASy, EBI, Israel, Japan]
Apperley J.F., Gardembas M., Melo J.V., Russell-Jones R., Bain B.J., Baxter E.J., Chase A., Chessells J.M., Colombat M., Dearden C.E., Dimitrijevic S., Mahon F.-X., Marin D., Nikolova Z., Olavarria E., Silberman S., Schultheis B., Cross N.C.P., Goldman J.M.;
"Response to imatinib mesylate in patients with chronic myeloproliferative diseases with rearrangements of the platelet-derived growth factor receptor beta.";
N. Engl. J. Med. 347:481-487(2002).
[14]
CHROMOSOMAL TRANSLOCATION WITH PDE4DIP.
DOI=10.1182/blood-2003-04-1150; PubMed=12907457 [NCBI, ExPASy, EBI, Israel, Japan]
Wilkinson K., Velloso E.R.P., Lopes L.F., Lee C., Aster J.C., Shipp M.A., Aguiar R.C.T.;
"Cloning of the t(1;5)(q23;q33) in a myeloproliferative disorder associated with eosinophilia: involvement of PDGFRB and response to imatinib.";
Blood 102:4187-4190(2003).
[15]
CHROMOSOMAL TRANSLOCATION WITH SPECC1.
DOI=10.1158/0008-5472.CAN-03-4026; PubMed=15087372 [NCBI, ExPASy, EBI, Israel, Japan]
Morerio C., Acquila M., Rosanda C., Rapella A., Dufour C., Locatelli F., Maserati E., Pasquali F., Panarello C.;
"HCMOGT-1 is a novel fusion partner to PDGFRB in juvenile myelomonocytic leukemia with t(5;17)(q33;p11.2).";
Cancer Res. 64:2649-2651(2004).
[16]
X-RAY CRYSTALLOGRAPHY (1.79 ANGSTROMS) OF 751-755 IN COMPLEX WITH PIK3R1, AND COMPARISON WITH NMR ANALYSIS.
DOI=10.1107/S0907444901012434; PubMed=11567151 [NCBI, ExPASy, EBI, Israel, Japan]
Pauptit R.A., Dennis C.A., Derbyshire D.J., Breeze A.L., Weston S.A., Rowsell S., Murshudov G.N.;
"NMR trial models: experiences with the colicin immunity protein Im7 and the p85alpha C-terminal SH2-peptide complex.";
Acta Crystallogr. D 57:1397-1404(2001).
[17]
X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS) OF 1102-1106 IN COMPLEX WITH SLC9A3R1 AND PDGFRA.
DOI=10.1074/jbc.M201507200; PubMed=11882663 [NCBI, ExPASy, EBI, Israel, Japan]
Karthikeyan S., Leung T., Ladias J.A.A.;
"Structural determinants of the Na+/H+ exchanger regulatory factor interaction with the beta 2 adrenergic and platelet-derived growth factor receptors.";
J. Biol. Chem. 277:18973-18978(2002).
[18]
VARIANTS [LARGE SCALE ANALYSIS] PHE-29; LYS-282; LYS-485; HIS-589; TYR-718 AND ILE-882.
DOI=10.1038/nature05610; PubMed=17344846 [NCBI, ExPASy, EBI, Israel, Japan]
Greenman C., Stephens P., Smith R., Dalgliesh G.L., Hunter C., Bignell G., Davies H., Teague J., Butler A., Stevens C., Edkins S., O'Meara S., Vastrik I., Schmidt E.E., Avis T., Barthorpe S., Bhamra G., Buck G., Choudhury B., Clements J., Cole J., Dicks E., Forbes S., Gray K., Halliday K., Harrison R., Hills K., Hinton J., Jenkinson A., Jones D., Menzies A., Mironenko T., Perry J., Raine K., Richardson D., Shepherd R., Small A., Tofts C., Varian J., Webb T., West S., Widaa S., Yates A., Cahill D.P., Louis D.N., Goldstraw P., Nicholson A.G., Brasseur F., Looijenga L., Weber B.L., Chiew Y.-E., DeFazio A., Greaves M.F., Green A.R., Campbell P., Birney E., Easton D.F., Chenevix-Trench G., Tan M.-H., Khoo S.K., Teh B.T., Yuen S.T., Leung S.Y., Wooster R., Futreal P.A., Stratton M.R.;
"Patterns of somatic mutation in human cancer genomes.";
Nature 446:153-158(2007).
Comments
  • FUNCTION: Receptor that binds specifically to PDGFB and PDGFD and has a tyrosine-protein kinase activity. Phosphorylates Tyr residues at the C-terminus of PTPN11 creating a binding site for the SH2 domain of GRB2.
  • CATALYTIC ACTIVITY: ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate.
  • SUBUNIT: Homodimer, and heterodimer with PDGFRA. Interacts with APS. The autophosphorylated form interacts directly with SHB and with PIK3C2B, maybe indirectly.
  • INTERACTION:
    P01127:PDGFB; NbExp=1; IntAct=EBI-641237, EBI-1554925;
    O00750:PIK3C2B; NbExp=1; IntAct=EBI-641237, EBI-641107;
  • SUBCELLULAR LOCATION: Membrane; Single-pass type I membrane protein.
  • DISEASE: A chromosomal aberration involving PDGFRB is found in a form of chronic myelomonocytic leukemia (CMML). Translocation t(5;12)(q33;p13) with EVT6/TEL. It is characterized by abnormal clonal myeloid proliferation and by progression to acute myelogenous leukemia (AML).
  • DISEASE: A chromosomal aberration involving PDGFRB may be a cause of acute myelogenous leukemia. Translocation t(5;14)(q33;q32) with TRIP11. The fusion protein may be involved in clonal evolution of leukemia and eosinophilia.
  • DISEASE: A chromosomal aberration involving PDGFRB may be a cause of juvenile myelomonocytic leukemia. Translocation t(5;17)(q33;p11.2) with SPECC1.
  • DISEASE: A chromosomal aberration involving PDGFRB is a cause in many instances of chronic myeloproliferative disorder with eosinophilia (MPE) [MIM:131440]. Translocation t(5;12) with ETV6 on chromosome 12 creating an PDGFRB-ETV6 fusion protein.
  • DISEASE: A chromosomal aberration involving PDGFRB may be the cause of a myeloproliferative disorder (MBD) associated with eosinophilia. Translocation t(1;5)(q23;q33) that forms a PDE4DIP-PDGFRB fusion protein.
  • SIMILARITY: Belongs to the protein kinase superfamily. Tyr protein kinase family. CSF-1/PDGF receptor subfamily.
  • SIMILARITY: Contains 5 Ig-like C2-type (immunoglobulin-like) domains.
  • SIMILARITY: Contains 1 protein kinase domain.
  • WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and Haematology; URL="http://atlasgeneticsoncology.org/Genes/PDGFRBID21ch5q32.html";.
Copyright
Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms. Distributed under the Creative Commons Attribution-NoDerivs License.
Cross-references
Sequence databases
EMBL
J03278; AAA60049.1; -; mRNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
M21616; AAA36427.1; -; mRNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
BC032224; AAH32224.1; -; mRNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
U33172; AAC51675.1; -; Genomic_DNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
PIR A28206; PFHUGB.
RefSeq NP_002600.1; -.
UniGene Hs.509067
3D structure databases
PDB
1GQ5; X-ray; 2.20 A; A=1102-1106.[ExPASy / RCSB / EBI]
1H9O; X-ray; 1.79 A; B=751-755.[ExPASy / RCSB / EBI]
1LWP; Model; -; A=600-962.[ExPASy / RCSB / EBI]
Detailed list of linked structures.
PDBsum 1GQ5; -.
1H9O; -.
1LWP; -.
ModBase P09619.
Protein-protein interaction databases
DIP DIP:558N; -.
IntAct P09619; 4.
PTM databases
PhosphoSite P09619; -.
Organism-specific databases
GeneCards GC05M149473; -.
H-InvDB HIX0024847; -.
HGNC HGNC:8804; PDGFRB.
GenAtlas PDGFRB.
HPA CAB003842; -.
CAB018144; -.
MIM 131440; phenotype. [NCBI / EBI]
173410; gene. [NCBI / EBI]
Orphanet 98823; Chronic myelomonocytic leukaemia.
86830; Chronic myeloproliferative disease, unclassifiable.
3260; Idiopathic hypereosinophilic syndrome.
86832; Myelodysplastic/myeloproliferative diseases, adult form.
98274; Myeloproliferative disease, chronic.
PharmGKB PA33148; -.
GeneCards P09619.
Gene expression databases
ArrayExpress P09619; -.
CleanEx HS_PDGFRB; -.
GermOnline ENSG00000113721; Homo sapiens.
Ontologies
GO
GO:0016021; Cellular component: integral to membrane (inferred from electronic annotation from UniProtKB-KW).
GO:0005524; Molecular function: ATP binding (inferred from electronic annotation from InterPro).
GO:0004992; Molecular function: platelet activating factor receptor activity (traceable author statement from ProtInc).
GO:0005019; Molecular function: platelet-derived growth factor beta-receptor activity (inferred from direct assay from UniProtKB).
GO:0048407; Molecular function: platelet-derived growth factor binding (inferred from physical interaction from UniProtKB).
GO:0005161; Molecular function: platelet-derived growth factor receptor binding (inferred from physical interaction from UniProtKB).
GO:0005021; Molecular function: vascular endothelial growth factor receptor activity (inferred from electronic annotation from InterPro).
GO:0048008; Biological process: platelet-derived growth factor receptor signaling pathway (inferred from direct assay from UniProtKB).
GO:0030335; Biological process: positive regulation of cell migration (inferred from direct assay from UniProtKB).
GO:0008284; Biological process: positive regulation of cell proliferation (inferred from direct assay from UniProtKB).
GO:0046777; Biological process: protein amino acid autophosphorylation (inferred from direct assay from UniProtKB).
QuickGo view.
Family and domain databases
InterPro IPR013151; Ig.
IPR007110; Ig-like.
IPR013783; Ig-like_fold.
IPR003599; Ig_sub.
IPR003598; Ig_sub2.
IPR000719; Prot_kinase_core.
IPR017441; Protein_kinase_ATP_bd_CS.
IPR001824; Recept_tyr_kinase-III_CS.
IPR001245; Tyr_pkinase.
IPR008266; Tyr_pkinase_AS.
IPR016243; TyrPK_CSF1-R.
IPR009134; VEGFR_N.
Graphical view of domain structure.
Gene3D G3DSA:2.60.40.10; Ig-like_fold; 3.
Pfam PF00047; ig; 2.
PF07714; Pkinase_Tyr; 1.
Pfam graphical view of domain structure.
PIRSF PIRSF000615; TyrPK_CSF1-R; 1.
PRINTS PR01832; VEGFRECEPTOR.
ProDom PD000001; Prot_kinase; 2.
[Domain structure / List of seq. sharing at least 1 domain]
SMART SM00409; IG; 2.
SM00408; IGc2; 1.
SM00219; TyrKc; 1.
SMART graphical view of domain structure.
PROSITE PS50835; IG_LIKE; 2.
PS00107; PROTEIN_KINASE_ATP; 1.
PS50011; PROTEIN_KINASE_DOM; 1.
PS00109; PROTEIN_KINASE_TYR; 1.
PS00240; RECEPTOR_TYR_KIN_III; 1.
PROSITE graphical view of domain structure (profiles).
Proteomics databases
PRIDE P09619; -.
Genome annotation databases
Ensembl ENSG00000113721; Homo sapiens. [Contig view]
GeneID 5159; -.
KEGG hsa:5159; -.
Phylogenomic databases
HOGENOM P09619; -.
HOVERGEN P09619; -.
Other
DrugBank DB00102; Becaplermin.
DB01254; Dasatinib.
DB00619; Imatinib.
DB00398; Sorafenib.
DB01268; Sunitinib.
LinkHub P09619; -.
NextBio 19958; -.
SOURCE PDGFRB; Homo sapiens.
ProtoNet P09619.
UniRef View cluster of proteins with at least 50% / 90% / 100% identity.
Keywords
3D-structure; ATP-binding; Chromosomal rearrangement; Direct protein sequencing; Glycoprotein; Immunoglobulin domain; Kinase; Membrane; Nucleotide-binding; Phosphoprotein; Polymorphism; Proto-oncogene; Receptor; Repeat; Signal; Transferase; Transmembrane; Tyrosine-protein kinase.
Features
SEVIEWER logo Feature table viewer FT aligner logo Feature aligner
KeyFrom   To Length Description FTId
SIGNAL   1     32  32      
CHAIN   33   1106  1074     Beta-type platelet-derived growth factor receptor. PRO_0000016757
TOPO_DOM   33    531  499     Extracellular (Potential). 
TRANSMEM   532    556  25     Potential. 
TOPO_DOM   557   1106  550     Cytoplasmic (Potential). 
DOMAIN   33    120  88     Ig-like C2-type 1. 
DOMAIN   129    210  82     Ig-like C2-type 2. 
DOMAIN   214    309  96     Ig-like C2-type 3. 
DOMAIN   331    403  73     Ig-like C2-type 4. 
DOMAIN   416    524  109     Ig-like C2-type 5. 
DOMAIN   600    962  363     Protein kinase. 
NP_BIND   606    614  9     ATP (By similarity). 
ACT_SITE   826    826        Proton acceptor (By similarity). 
BINDING   634    634        ATP (By similarity). 
SITE   527    528  2     Breakpoint for insertion to form PDE4DIP-PDGFRB fusion protein. 
SITE   527    528  2     Breakpoint for translocation to form TRIP11-PDGFRB. 
MOD_RES   751    751        Phosphotyrosine; by autocatalysis. 
MOD_RES   857    857        Phosphotyrosine; by autocatalysis. 
CARBOHYD   45     45        N-linked (GlcNAc...) (Potential). 
CARBOHYD   89     89        N-linked (GlcNAc...) (Potential). 
CARBOHYD   103    103        N-linked (GlcNAc...) (Potential). 
CARBOHYD   215    215        N-linked (GlcNAc...) (Potential). 
CARBOHYD   230    230        N-linked (GlcNAc...) (Potential). 
CARBOHYD   292    292        N-linked (GlcNAc...) (Potential). 
CARBOHYD   307    307        N-linked (GlcNAc...) (Potential). 
CARBOHYD   354    354        N-linked (GlcNAc...) (Potential). 
CARBOHYD   371    371        N-linked (GlcNAc...) (Potential). 
CARBOHYD   468    468        N-linked (GlcNAc...) (Potential). 
CARBOHYD   479    479        N-linked (GlcNAc...) (Potential). 
DISULFID   54    100        Potential. 
DISULFID   149    190        Potential. 
DISULFID   235    291        Potential. 
DISULFID   436    508        Potential. 
VARIANT   29     29  1     I -> F (in dbSNP:rs17110944 [NCBI]). VAR_034377 
VARIANT   180    180  1     S -> F (in dbSNP:rs17853027 [NCBI]). VAR_035125 
VARIANT   282    282  1     E -> K (in dbSNP:rs34586048 [NCBI]). VAR_042027 
VARIANT   345    345  1     P -> S (in dbSNP:rs2229558 [NCBI]). VAR_049717 
VARIANT   485    485  1     E -> K. VAR_042028 
VARIANT   589    589  1     Y -> H (in a gastric adenocarcinoma sample; somatic mutation). VAR_042029 
VARIANT   718    718  1     N -> Y. VAR_042030 
VARIANT   882    882  1     T -> I (in a breast infiltrating ductal carcinoma sample; somatic mutation). VAR_042031 
CONFLICT   241    241        E -> D (in Ref. 2; AAA36427). 
STRAND   601    603  3      
STRAND   606    613  8      
STRAND   615    617  3      
STRAND   620    624  5      
HELIX   628    631  4      
STRAND   632    634  3      
HELIX   641    649  9      
STRAND   671    673  3      
STRAND   675    678  4      
STRAND   681    685  5      
HELIX   686    695  10      
STRAND   700    702  3