PGFRB_HUMAN » Beta-type platelet-derived growth factor receptor

PGFRB_HUMAN » Beta-type platelet-derived growth factor receptor
Magnify PGFRB_HUMAN » Beta-type platelet-derived growth factor receptorEnlarged view of image
3D view in GLMol or JMol

gray dot

Download Coordinates

gray dot

Topology in Plasma membrane
Topologyextracellular side
cytoplasmic side
PGFRB_HUMAN » Beta-type platelet-derived growth factor receptor » PDGF-R-beta;CD140 antigen-like family member B;
Hydrophobic Thickness 36.4 ± 2.0 Å
Tilt Angle 2 ± 0°
ΔGtransfer -54.5 kcal/mol
ΔGfold -28.0 kcal/mol
Links UniProtKB, Pfam, Interpro, iHOP, STRING, HGNC, HMDB
Topology Out
TM Segments 527-559 (527-559)
Pathways

Calcium signaling pathway (KEGG)

Cytokine-cytokine receptor interaction (KEGG)

Focal adhesion (KEGG)

Gap junction (KEGG)

Glioma (KEGG)

HTLV-I infection (KEGG)

Immune System (Reactome)

MAPK signaling pathway (KEGG)

Melanoma (KEGG)

Pathways in cancer (KEGG)

PI3K-Akt signaling pathway (KEGG)

Prostate cancer (KEGG)

Regulation of actin cytoskeleton (KEGG)

Signal Transduction (Reactome)

PDB 1gq5 (1102-1106), 2l6w (A/B=526-563), 2pld (B=1018-1029), 2ple (B=1018-1029), 1h9o (B=751-755), 1sha (B=751-755), 3mjg (X/Y=33-314)
OPM 2l6w
Complexes

PGFRB:PGFRB_HUMAN

Interactions

EGFR, Complex: PGFRB:EGFR, PubMed

EPHB1, Complex: PGFRB:EPHB1, PubMed

ITB3, Complex: PGFRB:ITB3, PubMed

LRP6, Complex: LRP6:PGFRB, PubMed

PGFRA, Complex: NHRF1:PGFRA:PGFRB, PDBID: 1gq5

PGFRA, Complex: PGFRA:PGFRB, PubMed

PGFRB, Complex: Transmembrane homodimer of platelet-derived growth factor receptor beta, PDBID: 2L6W

PTN2, Complex: PGFRB:PTN2, PubMed

PTPRB, Complex: PGFRB:PTPRB

PTPRC, Complex: PTPRC:PGFRB

PTPRE, Complex: PGFRB:PTPRE

PTPRG, Complex: PGFRB:PTPRG

PTPRJ, Complex: PGFRB:PTPRJ, PubMed

PTPRK, Complex: PTPRK:PGFRB

PTPRO, Complex: PGFRB:PTPRO

PTPRR, Complex: PGFRB:PTPRR

Domains

AA: 37-114, PDBID: 3MJG, Subunit X, Seq Identity:100%, Immunoglobulin domain

AA: 213-295, PDBID: 3MJG, Subunit X, Seq Identity:100%, Immunoglobulin domain

AA: 327-413, PDBID: 1HCF, Subunit Y, Seq Identity:30%, Immunoglobulin I-set domain

AA: 600-958, PDBID: 1AYC, Subunit P, Seq Identity:100%, Protein tyrosine kinase

UniProt annotation for PGFRB_HUMAN » Beta-type platelet-derived growth factor receptor
FUNCTION: Tyrosine-protein kinase that acts as cell-surface receptor for homodimeric PDGFB and PDGFD and for heterodimers formed by PDGFA and PDGFB, and plays an essential role in the regulation of embryonic development, cell proliferation, survival, differentiation, chemotaxis and migration. Plays an essential role in blood vessel development by promoting proliferation, migration and recruitment of pericytes and smooth muscle cells to endothelial cells. Plays a role in the migration of vascular smooth muscle cells and the formation of neointima at vascular injury sites. Required for normal development of the cardiovascular system. Required for normal recruitment of pericytes (mesangial cells) in the kidney glomerulus, and for normal formation of a branched network of capillaries in kidney glomeruli. Promotes rearrangement of the actin cytoskeleton and the formation of membrane ruffles. Binding of its cognate ligands - homodimeric PDGFB, heterodimers formed by PDGFA and PDGFB or homodimeric PDGFD -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 PLCG1, PIK3R1, PTPN11, RASA1/GAP, CBL, SHC1 and NCK1. Activation of PLCG1 leads to the production of the cellular signaling molecules diacylglycerol and inositol 1,4,5- trisphosphate, mobilization of cytosolic Ca(2+) and the activation of protein kinase C. Phosphorylation of PIK3R1, the regulatory subunit of phosphatidylinositol 3-kinase, leads to the activation of the AKT1 signaling pathway. Phosphorylation of SHC1, or of the C-terminus of PTPN11, creates a binding site for GRB2, resulting in the activation of HRAS, RAF1 and down-stream MAP kinases, including MAPK1/ERK2 and/or MAPK3/ERK1. Promotes phosphorylation and activation of SRC family kinases. Promotes phosphorylation of PDCD6IP/ALIX and STAM. 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.

CATALYTIC ACTIVITY: ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate.

ENZYME REGULATION: Present in an inactive conformation in the absence of bound ligand. Binding of PDGFB and/or PDGFD leads to dimerization and activation by autophosphorylation on tyrosine residues. Inhibited by imatinib.

SUBUNIT: Interacts with homodimeric PDGFB and PDGFD, and with heterodimers formed by PDGFA and PDGFB. May also interact with homodimeric PDGFC. Monomer in the absence of bound ligand. Interaction with homodimeric PDGFB, heterodimers formed by PDGFA and PDGFB or homodimeric PDGFD, leads to receptor dimerization, where both PDGFRA homodimers and heterodimers with PDGFRB are observed. Interacts with SH2B2/APS. Interacts directly (tyrosine phosphorylated) with SHB. Interacts (tyrosine phosphorylated) with PIK3R1 and RASA1. Interacts (tyrosine phosphorylated) with CBL. Interacts (tyrosine phosphorylated) with SRC and SRC family kinases. Interacts (tyrosine phosphorylated) with PIK3C2B, maybe indirectly. Interacts (tyrosine phosphorylated) with SHC1, GRB7, GRB10 and NCK1. Interaction with GRB2 is mediated by SHC1. Interacts (via C-terminus) with SLC9A3R1.

DISEASE: Note=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: Myeloproliferative disorder chronic with eosinophilia (MPE) OMIM: A hematologic disorder characterized by malignant eosinophils proliferation. Note=The gene represented in this entry may be involved in disease pathogenesis. Chromosomal aberrations involving PDGFRB have been found in many instances of chronic myeloproliferative disorder with eosinophilia. Translocation t(5;12) with ETV6 on chromosome 12 creating an PDGFRB-ETV6 fusion protein (PubMed). Translocation t(5;15)(q33;q22) with TP53BP1 creating a PDGFRB-TP53BP1 fusion protein (PubMed). Translocation t(1;5)(q23;q33) that forms a PDE4DIP-PDGFRB fusion protein (PubMed). Translocation t(5;6)(q33-34;q23) with CEP85L that fuses the 5"-end of CEP85L (isoform 4) to the 3"-end of PDGFRB (PubMed).

DISEASE: Leukemia, acute myelogenous (AML) OMIM: A subtype of acute leukemia, a cancer of the white blood cells. AML is a malignant disease of bone marrow characterized by maturational arrest of hematopoietic precursors at an early stage of development. Clonal expansion of myeloid blasts occurs in bone marrow, blood, and other tissue. Myelogenous leukemias develop from changes in cells that normally produce neutrophils, basophils, eosinophils and monocytes. Note=The gene represented in this entry may be involved in disease pathogenesis. A chromosomal aberration involving PDGFRB has been found in a patient with AML. Translocation t(5;14)(q33;q32) with TRIP11 (PubMed).

DISEASE: Leukemia, juvenile myelomonocytic (JMML) OMIM: An aggressive pediatric myelodysplastic syndrome/myeloproliferative disorder characterized by malignant transformation in the hematopoietic stem cell compartment with proliferation of differentiated progeny. Patients have splenomegaly, enlarged lymph nodes, rashes, and hemorrhages. Note=The gene represented in this entry may be involved in disease pathogenesis. A chromosomal aberration involving PDGFRB has been found in a patient with JMML. Translocation t(5;17)(q33;p11.2) with SPECC1 (PubMed).

DISEASE: Basal ganglia calcification, idiopathic, 4 (IBGC4) OMIM: A form of basal ganglia calcification, an autosomal dominant condition characterized by symmetric calcification in the basal ganglia and other brain regions. Affected individuals can either be asymptomatic or show a wide spectrum of neuropsychiatric symptoms, including parkinsonism, dystonia, tremor, ataxia, dementia, psychosis, seizures, and chronic headache. Serum levels of calcium, phosphate, alkaline phosphatase and parathyroid hormone are normal. The neuropathological hallmark of the disease is vascular and pericapillary calcification, mainly of calcium phosphate, in the affected brain areas. mutations affecting the gene represented in this entry.

DISEASE: Myofibromatosis, infantile 1 (IMF1) OMIM: A rare mesenchymal disorder characterized by the development of benign tumors in the skin, striated muscles, bones, and, more rarely, visceral organs. Subcutaneous or soft tissue nodules commonly involve the skin of the head, neck, and trunk. Skeletal and muscular lesions occur in about half of the patients. Lesions may be solitary or multicentric, and they may be present at birth or become apparent in early infancy or occasionally in adult life. Visceral lesions are associated with high morbidity and mortality. Note=The disease is caused by mutations affecting the gene represented in this entry.

UniProt features for PGFRB_HUMAN » Beta-type platelet-derived growth factor receptor
SIGNAL 1 32
CHAIN 33 1106 Platelet-derived growth factor receptor beta.
DOMAIN 33 120 Ig-like C2-type 1.
DOMAIN 129 210 Ig-like C2-type 2.
DOMAIN 214 309 Ig-like C2-type 3.
DOMAIN 331 403 Ig-like C2-type 4.
DOMAIN 416 524 Ig-like C2-type 5.
DOMAIN 600 962 Protein kinase.
ACT_SITE 826 826 Proton acceptor (By similarity).
SITE 527 528 Breakpoint for insertion to form PDE4DIP- PDGFRB fusion protein.
SITE 527 528 Breakpoint for translocation to form TRIP11-PDGFRB.
SITE 558 559 Breakpoint for translocation to form the CEP85L-PDGFRB fusion protein.
DISULFID 54 100
DISULFID 149 190
DISULFID 235 291
DISULFID 436 508 By similarity.
Amino Acid Sequence for PGFRB_HUMAN » Beta-type platelet-derived growth factor receptor
MRLPGAMPAL ALKGELLLLS LLLLLEPQIS QGLVVTPPGP ELVLNVSSTF VLTCSGSAPV VWERMSQEPP QEMAKAQDGT FSSVLTLTNL TGLDTGEYFC THNDSRGLET DERKRLYIFV PDPTVGFLPN DAEELFIFLT EITEITIPCR VTDPQLVVTL HEKKGDVALP VPYDHQRGFS GIFEDRSYIC KTTIGDREVD SDAYYVYRLQ VSSINVSVNA VQTVVRQGEN ITLMCIVIGN EVVNFEWTYP RKESGRLVEP VTDFLLDMPY HIRSILHIPS AELEDSGTYT CNVTESVNDH QDEKAINITV VESGYVRLLG EVGTLQFAEL HRSRTLQVVF EAYPPPTVLW FKDNRTLGDS SAGEIALSTR NVSETRYVSE LTLVRVKVAE AGHYTMRAFH EDAEVQLSFQ LQINVPVRVL ELSESHPDSG EQTVRCRGRG MPQPNIIWSA CRDLKRCPRE LPPTLLGNSS EEESQLETNV TYWEEEQEFE VVSTLRLQHV DRPLSVRCTL RNAVGQDTQE VIVVPHSLPF KVVVISAILA LVVLTIISLI ILIMLWQKKP RYEIRWKVIE SVSSDGHEYI YVDPMQLPYD STWELPRDQL VLGRTLGSGA FGQVVEATAH GLSHSQATMK VAVKMLKSTA RSSEKQALMS ELKIMSHLGP HLNVVNLLGA CTKGGPIYII TEYCRYGDLV DYLHRNKHTF LQHHSDKRRP PSAELYSNAL PVGLPLPSHV SLTGESDGGY MDMSKDESVD YVPMLDMKGD VKYADIESSN YMAPYDNYVP SAPERTCRAT LINESPVLSY MDLVGFSYQV ANGMEFLASK NCVHRDLAAR NVLICEGKLV KICDFGLARD IMRDSNYISK GSTFLPLKWM APESIFNSLY TTLSDVWSFG ILLWEIFTLG GTPYPELPMN EQFYNAIKRG YRMAQPAHAS DEIYEIMQKC WEEKFEIRPP FSQLVLLLER LLGEGYKKKY QQVDEEFLRS DHPAILRSQA RLPGFHGLRS PLDTSSVLYT AVQPNEGDND YIIPLPDPKP EVADEGPLEG SPSLASSTLN EVNTSSTISC DSPLEPQDEP EPEPQLELQV EPEPELEQLP DSGCPAPRAE AEDSFL