Q05030 (PGFRB_RAT) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Platelet-derived growth factor receptor beta
Short name=PDGF-R-beta
Short name=PDGFR-beta
EC=2.7.10.1

Alternative name(s):
Beta platelet-derived growth factor receptor
Beta-type platelet-derived growth factor receptor
CD140 antigen-like family member B
Platelet-derived growth factor receptor 1
Short name=PDGFR-1
CD_antigen=CD140b

Gene names

Name:	Pdgfrb
Synonyms:	Pdgfr, Pdgfr1

Organism

Rattus norvegicus (Rat) [Reference proteome]

Taxonomic identifier

10116 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Rattus

Protein attributes

Sequence length	1097 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at transcript level

General annotation (Comments)

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 Ca2+ 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 By similarity.
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 By similarity.
Subunit structure	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. 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 By similarity.
Subcellular location	Cell membrane; Single-pass type I membrane protein By similarity. Cytoplasmic vesicle By similarity. Lysosome lumen By similarity. Note: After ligand binding, the autophosphorylated receptor is ubiquitinated and internalized, leading to its degradation By similarity.
Post-translational modification	N-glycosylated By similarity. Ubiquitinated. After autophosphorylation, the receptor is polyubiquitinated, leading to its degradation By similarity. Autophosphorylated on tyrosine residues upon ligand binding. Autophosphorylation occurs in trans, i.e. one subunit of the dimeric receptor phosphorylates tyrosine residues on the other subunit. Phosphorylation at Tyr-578, and to a lesser degree, Tyr-580 is important for interaction with SRC. Phosphorylation at Tyr-715 is important for interaction with GRB2. Phosphorylation at Tyr-739 and Tyr-750 is important for interaction with PIK3R1. Phosphorylation at Tyr-750 is important for interaction with NCK1. Phosphorylation at Tyr-770 and Tyr-856 is important for interaction with RASA1/GAP. Phosphorylation at Tyr-856 is important for efficient phosphorylation of PLCG1 and PTPN11, resulting in increased phosphorylation of AKT1, MAPK1/ERK2 and/or MAPK3/ERK1, PDCD6IP/ALIX and STAM, and in increased cell proliferation. Phosphorylation at Tyr-1008 is important for interaction with PTPN11. Phosphorylation at Tyr-1008 and Tyr-1020 is important for interaction with PLCG1. Dephosphorylated by PTPRJ at Tyr-750, Tyr-856, Tyr-1008 and Tyr-1020 By similarity.
Sequence similarities	Belongs to the protein kinase superfamily. Tyr protein kinase family. CSF-1/PDGF receptor subfamily. Contains 4 Ig-like C2-type (immunoglobulin-like) domains. Contains 1 protein kinase domain.

Ontologies

Keywords
Biological process	Chemotaxis
Cellular component	Cell membrane Cytoplasmic vesicle Lysosome Membrane
Domain	Immunoglobulin domain Repeat Signal Transmembrane Transmembrane helix
Ligand	ATP-binding Nucleotide-binding
Molecular function	Developmental protein Kinase Receptor Transferase Tyrosine-protein kinase
PTM	Disulfide bond Glycoprotein Phosphoprotein Ubl conjugation
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	adrenal gland development Inferred from electronic annotation. Source: Compara cardiac myofibril assembly Inferred from sequence or structural similarity. Source: UniProtKB cell chemotaxis Inferred from sequence or structural similarity. Source: UniProtKB cell migration involved in coronary angiogenesis Inferred from sequence or structural similarity. Source: UniProtKB cell migration involved in vasculogenesis Inferred from sequence or structural similarity. Source: UniProtKB glycosaminoglycan biosynthetic process Inferred from mutant phenotype PubMed 11903042. Source: RGD in utero embryonic development Inferred from electronic annotation. Source: Compara inner ear development Inferred from expression pattern PubMed 15267171. Source: RGD intracellular protein kinase cascade Inferred from mutant phenotype PubMed 18298916. Source: RGD metanephric S-shaped body morphogenesis Inferred from expression pattern PubMed 10734101. Source: UniProtKB metanephric comma-shaped body morphogenesis Inferred from expression pattern PubMed 10734101. Source: UniProtKB metanephric glomerular capillary formation Inferred from sequence or structural similarity. Source: UniProtKB metanephric glomerular mesangial cell proliferation involved in metanephros development Inferred from sequence or structural similarity. Source: UniProtKB metanephric mesenchymal cell migration Inferred from direct assay PubMed 10734101. Source: UniProtKB metanephric mesenchyme development Inferred from expression pattern PubMed 10734101. Source: UniProtKB negative regulation of apoptotic process Inferred from mutant phenotype PubMed 15978205. Source: RGD peptidyl-tyrosine phosphorylation Inferred from sequence or structural similarity. Source: UniProtKB phosphatidylinositol metabolic process Inferred from sequence or structural similarity. Source: UniProtKB phosphatidylinositol-mediated signaling Inferred from sequence or structural similarity. Source: UniProtKB positive regulation of DNA biosynthetic process Inferred from sequence or structural similarity. Source: UniProtKB positive regulation of ERK1 and ERK2 cascade Inferred from sequence or structural similarity. Source: UniProtKB positive regulation of MAP kinase activity Inferred from sequence or structural similarity. Source: UniProtKB positive regulation of calcium ion import Inferred from sequence or structural similarity. Source: UniProtKB positive regulation of cell proliferation by VEGF-activated platelet derived growth factor receptor signaling pathway Inferred from electronic annotation. Source: Compara positive regulation of chemotaxis Inferred from sequence or structural similarity. Source: UniProtKB positive regulation of collagen biosynthetic process Inferred from mutant phenotype PubMed 15978205. Source: RGD positive regulation of metanephric mesenchymal cell migration by platelet-derived growth factor receptor-beta signaling pathway Inferred from sequence or structural similarity. Source: UniProtKB positive regulation of mitosis Inferred from sequence or structural similarity. Source: UniProtKB positive regulation of phosphatidylinositol 3-kinase activity Inferred from sequence or structural similarity. Source: UniProtKB positive regulation of phosphatidylinositol 3-kinase cascade Inferred from sequence or structural similarity. Source: UniProtKB positive regulation of phospholipase C activity Inferred from sequence or structural similarity. Source: UniProtKB positive regulation of phosphoprotein phosphatase activity Inferred from electronic annotation. Source: Compara positive regulation of reactive oxygen species metabolic process Inferred from sequence or structural similarity. Source: UniProtKB positive regulation of smooth muscle cell migration Inferred from sequence or structural similarity. Source: UniProtKB positive regulation of smooth muscle cell proliferation Inferred from sequence or structural similarity. Source: UniProtKB protein autophosphorylation Inferred from sequence or structural similarity. Source: UniProtKB regulation of peptidyl-tyrosine phosphorylation Inferred from electronic annotation. Source: Compara response to estradiol stimulus Inferred from expression pattern PubMed 15039427. Source: RGD response to fluid shear stress Inferred from expression pattern PubMed 12738619. Source: RGD response to hydrogen peroxide Inferred from expression pattern PubMed 12226102. Source: RGD response to hyperoxia Inferred from expression pattern PubMed 15722379. Source: RGD response to retinoic acid Inferred from expression pattern PubMed 17303670. Source: RGD response to toxin Inferred from expression pattern PubMed 17654254. Source: RGD retina vasculature development in camera-type eye Inferred from sequence or structural similarity. Source: UniProtKB skeletal system morphogenesis Inferred from electronic annotation. Source: Compara smooth muscle tissue development Inferred from electronic annotation. Source: Compara tissue homeostasis Inferred from electronic annotation. Source: Compara transforming growth factor beta receptor signaling pathway Inferred from mutant phenotype PubMed 12819032. Source: RGD vascular endothelial growth factor receptor signaling pathway Inferred from electronic annotation. Source: InterPro wound healing Inferred from expression pattern PubMed 12533868. Source: RGD
Cellular_component	apical plasma membrane Inferred from direct assay PubMed 10550325. Source: UniProtKB cytoplasm Inferred from direct assay PubMed 10802145PubMed 11788434. Source: UniProtKB cytoplasmic membrane-bounded vesicle Inferred from electronic annotation. Source: UniProtKB-SubCell integral to plasma membrane Inferred from electronic annotation. Source: InterPro lysosomal lumen Inferred from electronic annotation. Source: UniProtKB-SubCell nucleus Inferred from direct assay PubMed 11788434. Source: UniProtKB
Molecular_function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW platelet-derived growth factor beta-receptor activity Inferred from sequence or structural similarity. Source: UniProtKB vascular endothelial growth factor-activated receptor activity Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Signal peptide	1 – 31	31	Potential
	Chain	32 – 1097	1066	Platelet-derived growth factor receptor beta		PRO_0000016759
Regions
	Topological domain	32 – 531	500	Extracellular Potential
	Transmembrane	532 – 552	21	Helical; Potential
	Topological domain	553 – 1097	545	Cytoplasmic Potential
	Domain	32 – 119	88	Ig-like C2-type 1
	Domain	128 – 209	82	Ig-like C2-type 2
	Domain	213 – 308	96	Ig-like C2-type 3
	Domain	415 – 523	109	Ig-like C2-type 4
	Domain	599 – 961	363	Protein kinase
	Nucleotide binding	605 – 613	9	ATP By similarity
Sites
	Active site	825	1	Proton acceptor By similarity
	Binding site	633	1	ATP By similarity
Amino acid modifications
	Modified residue	561	1	Phosphotyrosine; by autocatalysis By similarity
	Modified residue	578	1	Phosphotyrosine; by autocatalysis By similarity
	Modified residue	580	1	Phosphotyrosine; by autocatalysis By similarity
	Modified residue	588	1	Phosphotyrosine; by autocatalysis By similarity
	Modified residue	685	1	Phosphotyrosine; by ABL1 and ABL2 By similarity
	Modified residue	715	1	Phosphotyrosine; by autocatalysis By similarity
	Modified residue	739	1	Phosphotyrosine; by autocatalysis By similarity
	Modified residue	750	1	Phosphotyrosine; by autocatalysis By similarity
	Modified residue	762	1	Phosphotyrosine; by autocatalysis By similarity
	Modified residue	770	1	Phosphotyrosine; by autocatalysis By similarity
	Modified residue	774	1	Phosphotyrosine; by autocatalysis By similarity
	Modified residue	777	1	Phosphotyrosine; by autocatalysis By similarity
	Modified residue	856	1	Phosphotyrosine; by autocatalysis By similarity
	Modified residue	933	1	Phosphotyrosine; by ABL1 and ABL2 By similarity
	Modified residue	969	1	Phosphotyrosine; by ABL1 and ABL2 By similarity
	Modified residue	1008	1	Phosphotyrosine; by autocatalysis By similarity
	Modified residue	1020	1	Phosphotyrosine; by autocatalysis By similarity
	Glycosylation	44	1	N-linked (GlcNAc...) Potential
	Glycosylation	88	1	N-linked (GlcNAc...) Potential
	Glycosylation	102	1	N-linked (GlcNAc...) Potential
	Glycosylation	214	1	N-linked (GlcNAc...) Potential
	Glycosylation	291	1	N-linked (GlcNAc...) Potential
	Glycosylation	306	1	N-linked (GlcNAc...) Potential
	Glycosylation	353	1	N-linked (GlcNAc...) Potential
	Glycosylation	370	1	N-linked (GlcNAc...) Potential
	Glycosylation	444	1	N-linked (GlcNAc...) Potential
	Glycosylation	467	1	N-linked (GlcNAc...) Potential
	Glycosylation	478	1	N-linked (GlcNAc...) Potential
	Disulfide bond	53 ↔ 99		By similarity
	Disulfide bond	148 ↔ 189		By similarity
	Disulfide bond	234 ↔ 290		By similarity
	Disulfide bond	435 ↔ 507		By similarity

Sequences

	Sequence		Length	Mass (Da)
	Q05030 [UniParc]. Last modified July 25, 2003. Version 2. Checksum: 5E6540FA0C5CF22B	FASTA	1,097	122,828
	10 20 30 40 50 60 MGLPEVMPAS VLRGQLLLFV LLLLGPQISQ GLVITPPGPE FVLNISSTFV LTCSSSAPVM 70 80 90 100 110 120 WEQMSQVPWQ EAAMNQDGTF SSVLTLTNVT GGDTGEYFCV YNNSLGPELS ERKRIYIFVP 130 140 150 160 170 180 DPTMGFLPMD SEDLFIFVTD VTETTIPCRV TDPQLEVTLH EKKVDIPLHV PYDHQRGFIG 190 200 210 220 230 240 TFEDKTYICK TTIGDREVDS DTYYVYSLQV SSINVSVNAV QTVVRQGESI TIRCIVMGND 250 260 270 280 290 300 VVNFQWTYPR MKSGRLVEPV TDYLFGVPSR IGSILHIPTA ELSDSGTYTC NVSVSVNDHG 310 320 330 340 350 360 DEKAINVTVI ENGYVRLLET LEDVQIAELH RSRTLQVVFE AYPTPSVLWF KDNRTLGDSS 370 380 390 400 410 420 AGELVLSTRN VSETRYVSEL TLVRVKVSEA GYYTMRAFHA DDQVQLSFKL QVNVPVRVLE 430 440 450 460 470 480 LSESHPANGE QILRCRGRGM PQPNVTWSTC RDLKRCPRKL SPTPLGNSSK EESQLETNVT 490 500 510 520 530 540 FWEEDQEYEV VSTLRLRHVD QPLSVRCMLQ NSMGRDSQEV TVVPHSLPFK VVVISAILAL 550 560 570 580 590 600 VVLTVISLII LIMLWQRKPR YEIRWKVIES VSSDGHEYIY VDPVQLPYDS TWELPRDQLV 610 620 630 640 650 660 LGRTLGSGAF GQVVEATAHG LSHSQATMKV AVKMLKSTAR SSEKQALMSE LKIMSHLGPH 670 680 690 700 710 720 LNVVNLLGAC TKGGPIYIIT EYCRYGDLVD YLHRNKHTFL QRHSNKHCPP STELYSNALP 730 740 750 760 770 780 VGLSLPSHLN LTGESDGGYM DMSKDESVDY VPMLDMKGHI KYADIESSSY MAPYDNYVPS 790 800 810 820 830 840 APERTYRATL INDSPVLSYT DLVGFSYQVA NGMEFLASKN CVHRDLAARN VLICEGKLVK 850 860 870 880 890 900 ICDFGLARDI MRDSNYISKG STFLPLKWMA PESIFNSLYT TLSDVWSFGI LLWEIFTLGG 910 920 930 940 950 960 TPYPELPMND QFYNAIKRGY RMAQPAHASD EIYEIMQKCW EEKFETRPPF SQLVLLLERL 970 980 990 1000 1010 1020 LGEGYKKKYQ QVDEEFLRSD HPAILRSQAR LPGLHSLRSP LDTSSVLYTA VQPNETDNDY 1030 1040 1050 1060 1070 1080 IIPLPDPKPD AADEGLLEGS PSLASSTLNE VNTSSTISCD SPLELQEEPQ AEPEAQLEQP 1090 QDSGCPGPLA EAEDSFL

References

[1]	Wang Y., Culty M. Submitted (MAR-2002) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Strain: Sprague-Dawley.
[2]	"Conservation in sequence and affinity of human and rodent PDGF ligands and receptors." Herren B., Weyer K.A., Rouge M., Loetscher P., Pech M. Biochim. Biophys. Acta 1173:294-302(1993) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 35-533. Strain: Sprague-Dawley. Tissue: Brain.
[3]	"Regulation of cell growth by redox-mediated extracellular proteolysis of platelet-derived growth factor receptor beta." Okuyama H., Shimahara Y., Kawada N., Seki S., Kristensen D.B., Yoshizato K., Uyama N., Yamaoka Y. J. Biol. Chem. 276:28274-28280(2001) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 528-1090. Strain: Wistar.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AY090783 mRNA. Translation: AAM09098.1. Z14119 mRNA. Translation: CAA78489.1. AF359356 mRNA. Translation: AAK43716.1.
IPI	IPI00950587.
PIR	S33766.
RefSeq	NP_113713.1. NM_031525.1.
UniGene	Rn.98311.
3D structure databases
ProteinModelPortal	Q05030.
SMR	Q05030. Positions 558-706, 794-959.
ModBase	Search...
PTM databases
PhosphoSite	Q05030.
Proteomic databases
PaxDb	Q05030.
PRIDE	Q05030.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENSRNOT00000068535; ENSRNOP00000060534; ENSRNOG00000018461.
GeneID	24629.
KEGG	rno:24629.
UCSC	RGD:3285. rat.
Organism-specific databases
CTD	5159.
RGD	3285. Pdgfrb.
Phylogenomic databases
eggNOG	COG0515.
GeneTree	ENSGT00660000095142.
HOGENOM	HOG000112009.
HOVERGEN	HBG004335.
InParanoid	Q05030.
KO	K05089.
Gene expression databases
ArrayExpress	Q05030.
Genevestigator	Q05030.
GermOnline	ENSRNOG00000018461. Rattus norvegicus.
Family and domain databases
Gene3D	2.60.40.10. 5 hits.
InterPro	IPR007110. Ig-like_dom. IPR013783. Ig-like_fold. IPR013098. Ig_I-set. IPR003599. Ig_sub. IPR003598. Ig_sub2. IPR013151. Immunoglobulin. IPR011009. Kinase-like_dom. IPR027288. PGFRB. IPR000719. Prot_kinase_cat_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. IPR009134. Tyr_kinase_VEGFR_rcpt_N. [Graphical view]
Pfam	PF07679. I-set. 1 hit. PF00047. ig. 1 hit. PF07714. Pkinase_Tyr. 1 hit. [Graphical view]
PIRSF	PIRSF500948. Beta-PDGF_receptor. 1 hit. PIRSF000615. TyrPK_CSF1-R. 1 hit.
PRINTS	PR01832. VEGFRECEPTOR.
SMART	SM00409. IG. 2 hits. SM00408. IGc2. 1 hit. SM00219. TyrKc. 1 hit. [Graphical view]
SUPFAM	SSF56112. Kinase_like. 1 hit.
PROSITE	PS50835. IG_LIKE. 3 hits. PS00107. PROTEIN_KINASE_ATP. 1 hit. PS50011. PROTEIN_KINASE_DOM. 1 hit. PS00109. PROTEIN_KINASE_TYR. 1 hit. PS00240. RECEPTOR_TYR_KIN_III. 1 hit. [Graphical view]
ProtoNet	Search...
Other
BindingDB	Q05030.
ChEMBL	CHEMBL4125.
NextBio	603908.

Entry information

Entry name

PGFRB_RAT

Accession

Primary (citable) accession number: Q05030
Secondary accession number(s): Q8R406, Q925F7

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 1, 1997
Last sequence update:	July 25, 2003
Last modified:	May 1, 2013
This is version 127 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program