PGFRA_TAKRU
ID PGFRA_TAKRU Reviewed; 1062 AA.
AC Q8AXC7;
DT 05-SEP-2006, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2003, sequence version 1.
DT 03-AUG-2022, entry version 115.
DE RecName: Full=Platelet-derived growth factor receptor alpha;
DE Short=PDGF-R-alpha;
DE Short=PDGFR-alpha;
DE EC=2.7.10.1;
DE AltName: Full=Alpha platelet-derived growth factor receptor;
DE AltName: Full=Alpha-type platelet-derived growth factor receptor;
DE Flags: Precursor;
GN Name=pdgfra;
OS Takifugu rubripes (Japanese pufferfish) (Fugu rubripes).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Actinopterygii; Neopterygii; Teleostei; Neoteleostei; Acanthomorphata;
OC Eupercaria; Tetraodontiformes; Tetradontoidea; Tetraodontidae; Takifugu.
OX NCBI_TaxID=31033;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=12592706; DOI=10.1080/1042517021000011627;
RA Williams H., Brenner S., Venkatesh B.;
RT "Characterization of the platelet-derived growth factor receptor alpha and
RT c-kit genes in the pufferfish Fugu rubripes.";
RL DNA Seq. 13:263-270(2002).
CC -!- FUNCTION: Tyrosine-protein kinase that acts as a cell-surface receptor
CC for pdgfa, pdgfb and pdgfc and plays an essential role in the
CC regulation of embryonic development, cell proliferation, survival and
CC chemotaxis. Depending on the context, promotes or inhibits cell
CC proliferation and cell migration. Plays an important role in the
CC differentiation of bone marrow-derived mesenchymal stem cells. Required
CC for normal skeleton development. Required for normal development of the
CC gastrointestinal tract. Plays a role in cell migration and chemotaxis
CC in wound healing. Plays a role in platelet activation, secretion of
CC agonists from platelet granules, and in thrombin-induced platelet
CC aggregation. Binding of its cognate ligands - homodimeric pdgfa,
CC homodimeric pdgfb, heterodimers formed by pdgfa and pdgfb or
CC homodimeric pdgfc -leads to the activation of several signaling
CC cascades; the response depends on the nature of the bound ligand and is
CC modulated by the formation of heterodimers between pdgfra and pdgfrb.
CC Phosphorylates pik3r1, plcg1, and ptpn11. Activation of plcg1 leads to
CC the 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. Phosphorylates pik3r1, the regulatory
CC subunit of phosphatidylinositol 3-kinase, and thereby mediates
CC activation of the AKT1 signaling pathway. Mediates activation of hras
CC and of the MAP kinases mapk1/erk2 and/or mapk3/erk1. Promotes
CC activation of STAT family members stat1, stat3 and stat5a and/or
CC stat5b. Receptor signaling is down-regulated by protein phosphatases
CC that 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 pdgfa and/or pdgfb leads to dimerization
CC and activation by autophosphorylation on tyrosine residues (By
CC similarity). {ECO:0000250}.
CC -!- SUBUNIT: Interacts with homodimeric pdgfa, pdgfb and pdgfc, and with
CC heterodimers formed by pdgfa and pdgfb. monomer in the absence of bound
CC ligand. Interaction with dimeric pdgfa, pdgfb and/or pdgfc leads to
CC receptor dimerization, where both pdgfra homodimers and heterodimers
CC with pdgfrb are observed (By similarity). {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250}; Single-pass type I
CC membrane protein {ECO:0000250}. Note=The activated receptor is rapidly
CC internalized and degraded. {ECO:0000250}.
CC -!- PTM: Ubiquitinated, leading to its degradation. {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 (By
CC 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}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; AF456419; AAN87554.1; -; Genomic_DNA.
DR AlphaFoldDB; Q8AXC7; -.
DR SMR; Q8AXC7; -.
DR STRING; 31033.ENSTRUP00000038529; -.
DR eggNOG; KOG0200; Eukaryota.
DR InParanoid; Q8AXC7; -.
DR Proteomes; UP000005226; Unplaced.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0005018; F:platelet-derived growth factor alpha-receptor activity; IEA:InterPro.
DR GO; GO:0006935; P:chemotaxis; IEA:UniProtKB-KW.
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; IPR011009; Kinase-like_dom_sf.
DR InterPro; IPR027290; PDGFRA.
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; 2.
DR Pfam; PF07714; PK_Tyr_Ser-Thr; 1.
DR PIRSF; PIRSF500950; Alpha-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 3: Inferred from homology;
KW ATP-binding; Cell membrane; Chemotaxis; Developmental protein;
KW Disulfide bond; Glycoprotein; Immunoglobulin domain; Kinase; Membrane;
KW Nucleotide-binding; Phosphoprotein; Receptor; Reference proteome; Repeat;
KW Signal; Transferase; Transmembrane; Transmembrane helix;
KW Tyrosine-protein kinase; Ubl conjugation.
FT SIGNAL 1..27
FT /evidence="ECO:0000255"
FT CHAIN 28..1062
FT /note="Platelet-derived growth factor receptor alpha"
FT /id="PRO_0000248885"
FT TOPO_DOM 28..504
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 505..525
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 526..1062
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 28..96
FT /note="Ig-like C2-type 1"
FT DOMAIN 91..184
FT /note="Ig-like C2-type 2"
FT DOMAIN 190..281
FT /note="Ig-like C2-type 3"
FT DOMAIN 287..381
FT /note="Ig-like C2-type 4"
FT DOMAIN 389..493
FT /note="Ig-like C2-type 5"
FT DOMAIN 569..945
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT REGION 734..754
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 975..1034
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1002..1017
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1018..1034
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 793
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT ECO:0000255|PROSITE-ProRule:PRU10028"
FT BINDING 575..583
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 603
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT MOD_RES 548
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000250"
FT MOD_RES 550
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000250"
FT MOD_RES 697
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000250"
FT MOD_RES 708
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000250"
FT MOD_RES 719
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000250"
FT MOD_RES 731
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000250"
FT MOD_RES 739
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000250"
FT MOD_RES 824
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000250"
FT MOD_RES 963
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000250"
FT MOD_RES 992
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000250"
FT CARBOHYD 79
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 132
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 273
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 333
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 366
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 433
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 444
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 29..74
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
FT DISULFID 124..165
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
FT DISULFID 211..265
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
FT DISULFID 410..477
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
SQ SEQUENCE 1062 AA; 118638 MW; 5439854FE174B832 CRC64;
MFPPSSAPLL LPQLEELVVP LHTAFTLTCQ GEATIAWDVP LDVPEKTQED NSGLFVTTIS
VDSASAMHTG YYRCFYRRNA TEDADEAMQS IYVYVPDPDV PFVPLVVPFG NHVLSDHEEM
EIQCRVSDPS ANVTLINVDT QQPVPCMYDS KRGALGVFTA GTYVCKGVVN GAEHYSEDYI
VHGWIGGSGL HVELTAKHTV LLVGDTITVN CLAQGSEILE DHWKYPGKVA NRAIKTVHEN
KKDQEILYTL TVPQASVKDT GIYSCSITDV VTNMSQTKQI AIRVYASEFM SIQPKFGEYE
SAELDEVCEF RAEITSFPTA SVTWFKDSVP LSNVTAEIST SLQKLSETSY MSVLTLIRAK
EEDSGNYTMR VKNGDQSRTV SLILEVKVPA VIVDLMDIHH GSATGQSVVC ITRGQPTPLV
EWFVCKNIKH CANDTSSWVP LPVNSTEVTM DSRFDEDNNL ETQVIFGHLE NTLAVRCLAR
NEMAAVSREI KLVSNGPHPE LTVAAAVLVL LVIVIISLIV LVVIWKQKPR YEIRWRVIES
VSPDGHEYIY VDPMQLPYDS RWEFPRDRLV LGRILGSGAF GKVVEGTAYG LSRSQPVMKV
AVKMLKPTAR SSEKQALMSE LKIMTHLGPH LNIVNLLGAC TKSGPIYIIT EYCFYGDLVN
YLHKNRESFL NPKPEKSNKK ELDIFGINPA DESSRSYVIL SFESKGDYMD MKQADNTQYV
PMLEISNASK YSDLQGSNYD HPPSQKGSND GEMDQLLSDN MSEGLTTNDL LSFTYQVAKG
MEFLASKNCV HRDLAARNVL LSQGKIVKIC DFGLARDIMH DNNYVSKGST FLPVKWMAPE
SIFDNLYTTL SDVWSYGILL WEIFSLGGTP YPGMIVDSSF YNKIKSGYRM SKPEHAPQDV
YDMMMKCWNS EPEKRPSFLG LSDTIASLLP SSYKRHYERV NHEFLKSDHP AVTRVCVDND
DAYIGITYKN QGKLKDRESG FDEQRLSSDS GYIIPLPDLD PISDEEYGKR NRHSSQTSEE
SAIETGSSSS TFAKREGETL EDITLLDEMC LDCSDLVEDS FL
