PGFRB_CANLF
ID PGFRB_CANLF Reviewed; 1103 AA.
AC Q6QNF3;
DT 13-SEP-2005, integrated into UniProtKB/Swiss-Prot.
DT 05-JUL-2004, sequence version 1.
DT 03-AUG-2022, entry version 136.
DE RecName: Full=Platelet-derived growth factor receptor beta;
DE Short=PDGF-R-beta;
DE Short=PDGFR-beta;
DE EC=2.7.10.1;
DE AltName: Full=Beta platelet-derived growth factor receptor;
DE AltName: Full=Beta-type platelet-derived growth factor receptor;
DE AltName: Full=CD140 antigen-like family member B;
DE AltName: Full=Platelet-derived growth factor receptor 1;
DE Short=PDGFR-1;
DE AltName: CD_antigen=CD140b;
DE Flags: Precursor;
GN Name=PDGFRB; Synonyms=PDGFR, PDGFR1;
OS Canis lupus familiaris (Dog) (Canis familiaris).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Carnivora; Caniformia; Canidae; Canis.
OX NCBI_TaxID=9615;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RA Liao A.T., Chien M.B., London C.A.;
RT "Characterization of PDGFb on the histiocytic sarcoma.";
RL Submitted (JAN-2004) to the EMBL/GenBank/DDBJ databases.
CC -!- FUNCTION: Tyrosine-protein kinase that acts as cell-surface receptor
CC for homodimeric PDGFB and PDGFD and for heterodimers formed by PDGFA
CC and PDGFB, and plays an essential role in the regulation of embryonic
CC development, cell proliferation, survival, differentiation, chemotaxis
CC and migration. Plays an essential role in blood vessel development by
CC promoting proliferation, migration and recruitment of pericytes and
CC smooth muscle cells to endothelial cells. Plays a role in the migration
CC of vascular smooth muscle cells and the formation of neointima at
CC vascular injury sites. Required for normal development of the
CC cardiovascular system. Required for normal recruitment of pericytes
CC (mesangial cells) in the kidney glomerulus, and for normal formation of
CC a branched network of capillaries in kidney glomeruli. Promotes
CC rearrangement of the actin cytoskeleton and the formation of membrane
CC ruffles. Binding of its cognate ligands - homodimeric PDGFB,
CC heterodimers formed by PDGFA and PDGFB or homodimeric PDGFD -leads to
CC the activation of several signaling cascades; the response depends on
CC the nature of the bound ligand and is modulated by the formation of
CC heterodimers between PDGFRA and PDGFRB. Phosphorylates PLCG1, PIK3R1,
CC PTPN11, RASA1/GAP, CBL, SHC1 and NCK1. Activation of PLCG1 leads to the
CC production of the cellular signaling molecules diacylglycerol and
CC inositol 1,4,5-trisphosphate, mobilization of cytosolic Ca(2+) and the
CC activation of protein kinase C. Phosphorylation of PIK3R1, the
CC regulatory subunit of phosphatidylinositol 3-kinase, leads to the
CC activation of the AKT1 signaling pathway. Phosphorylation of SHC1, or
CC of the C-terminus of PTPN11, creates a binding site for GRB2, resulting
CC in the activation of HRAS, RAF1 and down-stream MAP kinases, including
CC MAPK1/ERK2 and/or MAPK3/ERK1. Promotes phosphorylation and activation
CC of SRC family kinases. Promotes phosphorylation of PDCD6IP/ALIX and
CC STAM. Receptor signaling is down-regulated by protein phosphatases that
CC dephosphorylate the receptor and its down-stream effectors, and by
CC rapid internalization of the activated receptor (By similarity).
CC {ECO:0000250}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-tyrosyl-[protein] = ADP + H(+) + O-phospho-L-tyrosyl-
CC [protein]; Xref=Rhea:RHEA:10596, Rhea:RHEA-COMP:10136, Rhea:RHEA-
CC COMP:10137, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:46858,
CC ChEBI:CHEBI:82620, ChEBI:CHEBI:456216; EC=2.7.10.1;
CC Evidence={ECO:0000255|PROSITE-ProRule:PRU10028};
CC -!- ACTIVITY REGULATION: Present in an inactive conformation in the absence
CC of bound ligand. Binding of PDGFB and/or PDGFD leads to dimerization
CC and activation by autophosphorylation on tyrosine residues (By
CC similarity). {ECO:0000250}.
CC -!- SUBUNIT: Interacts with homodimeric PDGFB and PDGFD, and with
CC heterodimers formed by PDGFA and PDGFB. May also interact with
CC homodimeric PDGFC. Monomer in the absence of bound ligand. Interaction
CC with homodimeric PDGFB, heterodimers formed by PDGFA and PDGFB or
CC homodimeric PDGFD, leads to receptor dimerization, where both PDGFRA
CC homodimers and heterodimers with PDGFRB are observed. Interacts with
CC SH2B2/APS. Interacts directly (tyrosine phosphorylated) with SHB.
CC Interacts (tyrosine phosphorylated) with PIK3R1 and RASA1. Interacts
CC (tyrosine phosphorylated) with CBL. Interacts (tyrosine phosphorylated)
CC with SRC and SRC family kinases. Interacts (tyrosine phosphorylated)
CC with PIK3C2B, maybe indirectly. Interacts (tyrosine phosphorylated)
CC with SHC1, GRB7, GRB10 and NCK1. Interaction with GRB2 is mediated by
CC SHC1. Interacts (via C-terminus) with SLC9A3R1 (By similarity).
CC {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250}; Single-pass type I
CC membrane protein {ECO:0000250}. Cytoplasmic vesicle {ECO:0000250}.
CC Lysosome lumen {ECO:0000250}. Note=After ligand binding, the
CC autophosphorylated receptor is ubiquitinated and internalized, leading
CC to its degradation. {ECO:0000250}.
CC -!- PTM: N-glycosylated. {ECO:0000250}.
CC -!- PTM: Ubiquitinated. After autophosphorylation, the receptor is
CC polyubiquitinated, leading to its degradation (By similarity).
CC {ECO:0000250}.
CC -!- PTM: Autophosphorylated on tyrosine residues upon ligand binding.
CC Autophosphorylation occurs in trans, i.e. one subunit of the dimeric
CC receptor phosphorylates tyrosine residues on the other subunit.
CC Phosphorylation at Tyr-579, and to a lesser degree, Tyr-581 is
CC important for interaction with SRC. Phosphorylation at Tyr-716 is
CC important for interaction with GRB2. Phosphorylation at Tyr-740 and
CC Tyr-751 is important for interaction with PIK3R1. Phosphorylation at
CC Tyr-751 is important for interaction with NCK1. Phosphorylation at Tyr-
CC 771 and Tyr-857 is important for interaction with RASA1/GAP.
CC Phosphorylation at Tyr-857 is important for efficient phosphorylation
CC of PLCG1 and PTPN11, resulting in increased phosphorylation of AKT1,
CC MAPK1/ERK2 and/or MAPK3/ERK1, PDCD6IP/ALIX and STAM, and in increased
CC cell proliferation. Phosphorylation at Tyr-1009 is important for
CC interaction with PTPN11. Phosphorylation at Tyr-1009 and Tyr-1021 is
CC important for interaction with PLCG1. Dephosphorylated by PTPRJ at Tyr-
CC 751, Tyr-857, Tyr-1009 and Tyr-1021 (By similarity). Dephosphorylated
CC by PTPN2 at Tyr-579 and Tyr-1021 (By similarity). {ECO:0000250}.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. Tyr protein
CC kinase family. CSF-1/PDGF receptor subfamily. {ECO:0000255|PROSITE-
CC ProRule:PRU00159}.
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DR EMBL; AY532634; AAS48371.1; -; mRNA.
DR RefSeq; NP_001003382.1; NM_001003382.1.
DR RefSeq; XP_005618929.1; XM_005618872.2.
DR RefSeq; XP_005618930.1; XM_005618873.2.
DR AlphaFoldDB; Q6QNF3; -.
DR BMRB; Q6QNF3; -.
DR SMR; Q6QNF3; -.
DR BioGRID; 140028; 1.
DR STRING; 9612.ENSCAFP00000000714; -.
DR PaxDb; Q6QNF3; -.
DR GeneID; 442985; -.
DR KEGG; cfa:442985; -.
DR CTD; 5159; -.
DR eggNOG; KOG0200; Eukaryota.
DR InParanoid; Q6QNF3; -.
DR Proteomes; UP000002254; Unplaced.
DR GO; GO:0016324; C:apical plasma membrane; ISS:UniProtKB.
DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR GO; GO:0031410; C:cytoplasmic vesicle; IEA:UniProtKB-KW.
DR GO; GO:0005887; C:integral component of plasma membrane; IBA:GO_Central.
DR GO; GO:0031226; C:intrinsic component of plasma membrane; ISS:UniProtKB.
DR GO; GO:0043202; C:lysosomal lumen; IEA:UniProtKB-SubCell.
DR GO; GO:0005634; C:nucleus; ISS:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; ISS:UniProtKB.
DR GO; GO:0043235; C:receptor complex; IBA:GO_Central.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0019838; F:growth factor binding; IBA:GO_Central.
DR GO; GO:0005019; F:platelet-derived growth factor beta-receptor activity; ISS:UniProtKB.
DR GO; GO:0048407; F:platelet-derived growth factor binding; IBA:GO_Central.
DR GO; GO:0004714; F:transmembrane receptor protein tyrosine kinase activity; IBA:GO_Central.
DR GO; GO:0001525; P:angiogenesis; IBA:GO_Central.
DR GO; GO:0060326; P:cell chemotaxis; IBA:GO_Central.
DR GO; GO:0016477; P:cell migration; ISS:UniProtKB.
DR GO; GO:0060981; P:cell migration involved in coronary angiogenesis; ISS:UniProtKB.
DR GO; GO:0035441; P:cell migration involved in vasculogenesis; ISS:UniProtKB.
DR GO; GO:0018108; P:peptidyl-tyrosine phosphorylation; ISS:UniProtKB.
DR GO; GO:0046488; P:phosphatidylinositol metabolic process; ISS:UniProtKB.
DR GO; GO:0048015; P:phosphatidylinositol-mediated signaling; ISS:UniProtKB.
DR GO; GO:0048008; P:platelet-derived growth factor receptor signaling pathway; ISS:UniProtKB.
DR GO; GO:0008284; P:positive regulation of cell population proliferation; ISS:UniProtKB.
DR GO; GO:0070374; P:positive regulation of ERK1 and ERK2 cascade; ISS:UniProtKB.
DR GO; GO:0033674; P:positive regulation of kinase activity; IBA:GO_Central.
DR GO; GO:0043552; P:positive regulation of phosphatidylinositol 3-kinase activity; ISS:UniProtKB.
DR GO; GO:0010863; P:positive regulation of phospholipase C activity; ISS:UniProtKB.
DR GO; GO:0032516; P:positive regulation of phosphoprotein phosphatase activity; ISS:UniProtKB.
DR GO; GO:0014911; P:positive regulation of smooth muscle cell migration; ISS:UniProtKB.
DR GO; GO:0048661; P:positive regulation of smooth muscle cell proliferation; ISS:UniProtKB.
DR GO; GO:0046777; P:protein autophosphorylation; ISS:UniProtKB.
DR GO; GO:0061298; P:retina vasculature development in camera-type eye; ISS:UniProtKB.
DR GO; GO:0007169; P:transmembrane receptor protein tyrosine kinase signaling pathway; IBA:GO_Central.
DR Gene3D; 2.60.40.10; -; 5.
DR InterPro; IPR007110; Ig-like_dom.
DR InterPro; IPR036179; Ig-like_dom_sf.
DR InterPro; IPR013783; Ig-like_fold.
DR InterPro; IPR013098; Ig_I-set.
DR InterPro; IPR003599; Ig_sub.
DR InterPro; IPR003598; Ig_sub2.
DR InterPro; IPR013151; Immunoglobulin.
DR InterPro; IPR011009; Kinase-like_dom_sf.
DR InterPro; IPR027288; PGFRB.
DR InterPro; IPR000719; Prot_kinase_dom.
DR InterPro; IPR017441; Protein_kinase_ATP_BS.
DR InterPro; IPR001245; Ser-Thr/Tyr_kinase_cat_dom.
DR InterPro; IPR008266; Tyr_kinase_AS.
DR InterPro; IPR020635; Tyr_kinase_cat_dom.
DR InterPro; IPR001824; Tyr_kinase_rcpt_3_CS.
DR Pfam; PF07679; I-set; 1.
DR Pfam; PF00047; ig; 1.
DR Pfam; PF07714; PK_Tyr_Ser-Thr; 1.
DR PIRSF; PIRSF500948; Beta-PDGF_receptor; 1.
DR SMART; SM00409; IG; 3.
DR SMART; SM00408; IGc2; 3.
DR SMART; SM00219; TyrKc; 1.
DR SUPFAM; SSF48726; SSF48726; 3.
DR SUPFAM; SSF56112; SSF56112; 1.
DR PROSITE; PS50835; IG_LIKE; 2.
DR PROSITE; PS00107; PROTEIN_KINASE_ATP; 1.
DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 1.
DR PROSITE; PS00109; PROTEIN_KINASE_TYR; 1.
DR PROSITE; PS00240; RECEPTOR_TYR_KIN_III; 1.
PE 2: Evidence at transcript level;
KW ATP-binding; Cell membrane; Chemotaxis; Cytoplasmic vesicle;
KW Developmental protein; Disulfide bond; Glycoprotein; Immunoglobulin domain;
KW Kinase; Lysosome; Membrane; Nucleotide-binding; Phosphoprotein; Receptor;
KW Reference proteome; Repeat; Signal; Transferase; Transmembrane;
KW Transmembrane helix; Tyrosine-protein kinase; Ubl conjugation.
FT SIGNAL 1..31
FT /evidence="ECO:0000255"
FT CHAIN 32..1103
FT /note="Platelet-derived growth factor receptor beta"
FT /id="PRO_0000041843"
FT TOPO_DOM 33..532
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 533..553
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 554..1103
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 33..120
FT /note="Ig-like C2-type 1"
FT DOMAIN 129..210
FT /note="Ig-like C2-type 2"
FT DOMAIN 214..309
FT /note="Ig-like C2-type 3"
FT DOMAIN 331..403
FT /note="Ig-like C2-type 4"
FT DOMAIN 416..524
FT /note="Ig-like C2-type 5"
FT DOMAIN 600..962
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT REGION 1017..1103
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1039..1062
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1075..1090
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 826
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT ECO:0000255|PROSITE-ProRule:PRU10028"
FT BINDING 606..614
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 634
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT MOD_RES 562
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000250|UniProtKB:P09619"
FT MOD_RES 579
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000250|UniProtKB:P09619"
FT MOD_RES 581
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000250|UniProtKB:P09619"
FT MOD_RES 686
FT /note="Phosphotyrosine; by ABL1 and ABL2"
FT /evidence="ECO:0000250|UniProtKB:P05622"
FT MOD_RES 716
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000250|UniProtKB:P09619"
FT MOD_RES 740
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000250|UniProtKB:P09619"
FT MOD_RES 751
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000250|UniProtKB:P09619"
FT MOD_RES 763
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000250|UniProtKB:P09619"
FT MOD_RES 771
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000250|UniProtKB:P09619"
FT MOD_RES 775
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000250|UniProtKB:P09619"
FT MOD_RES 778
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000250|UniProtKB:P09619"
FT MOD_RES 857
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000250|UniProtKB:P09619"
FT MOD_RES 934
FT /note="Phosphotyrosine; by ABL1 and ABL2"
FT /evidence="ECO:0000250|UniProtKB:P05622"
FT MOD_RES 970
FT /note="Phosphotyrosine; by ABL1 and ABL2"
FT /evidence="ECO:0000250|UniProtKB:P05622"
FT MOD_RES 1009
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000250|UniProtKB:P09619"
FT MOD_RES 1021
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000250|UniProtKB:P09619"
FT CARBOHYD 45
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 89
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 215
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 230
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 292
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 307
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 354
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 371
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 468
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 479
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 54..100
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
FT DISULFID 149..190
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
FT DISULFID 235..291
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
FT DISULFID 436..508
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
SQ SEQUENCE 1103 AA; 123022 MW; A3D66E78A34C5FE0 CRC64;
MQVPGTMPAP VLKGQALWLP LLLMLSPQAS GGLVITPPGP ELVLNISSTF VLTCSGPAPV
VWERLSQEPL QKMARTQDGT FSSTLTLTNV TGLDTGEYFC TYKGSHGLEP DGRKRLYIFV
PDPTMGFLPV DPEELFIFLT EITEITIPCR VTDPRLVVTL HEKKVDIPLP IPYDHQRGFS
GTFEDKTYVC KTTIGDKEVD SEAYYVYSLQ VSSINVSVNA VQTVVRQGEN ITIMCIVTGN
EVVNFEWTYP RMESGRLVEP VTDFLFNVPS HIRSILHIPS AELGDSGTYI CNVSESVNDH
RDEKSINVTV VESGYVRLLG ELDAVQFAEL HRSRALQVVF EAYPPPTVVW FKDNRTLGDS
SAGEIALSTR NVSETRYVSE LTLVRVKVAE AGYYTMRAFH EDAEAQLSFQ LQVNVPVRVL
ELSESHPASG EQTVRCRGRG MPQPHLTWST CSDLKRCPRE LPPTPLGNSS EEESQLETNV
TYWPEDQEFE VVSTLRLRRV DQPLSVRCTL HNLLGHDMQE VTVVPHSLPF KVVVISAILA
LVVLTIISLI ILIMLWQKKP RYEIRWKVIE SVSSDGHEYI YVDPMQLPYD STWELPRDQL
VLGRTLGSGA FGQVVEATAH GLSHSQATMK VAVKMLKSTA RSSEKQALMS ELKIMSHLGP
HLNVVNLLGA CTKGGPIYII TEYCRYGDLV DYLHRNKHTF LQLCSDKRRP PSAELYSNAL
PAGLPLPSHV SLPGESDGGY MDMSKDESVD YVPMLDMKGG VKYADIESSS YMAPYDNYVP
TAPERTCRAT LINESPVLSY TDLVGFSYQV ANGMEFLASK NCVHRDLAAR NVLICEGKLV
KICDFGLARD IMRDSNYISK GSTFLPLKWM APESIFNSLY TTLSDVWSFG ILLWEIFTLG
GTPYPELPMN EQFYNAIKRG YRMAQPAHAS DEIYEIMQKC WEEKFEIRPP FSQLVLLLER
LLGEGYKKKY QQVDEEFLRS DHPAVLRSQA RLPGFPGLRS PLDTSSVLYT AVQPNEGDND
YIIPLPDPKP EVADGPLESS PSLASSTLNE VNTSSTISCD SPLEPQEEPE PEPEPQPEPQ
VVPEPPLDSS CPGPRAEAED SFL
