PGFRA_CHICK
ID PGFRA_CHICK Reviewed; 1087 AA.
AC Q9PUF6;
DT 05-SEP-2006, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-2000, sequence version 1.
DT 03-AUG-2022, entry version 134.
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 Gallus gallus (Chicken).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Archelosauria; Archosauria; Dinosauria; Saurischia; Theropoda;
OC Coelurosauria; Aves; Neognathae; Galloanserae; Galliformes; Phasianidae;
OC Phasianinae; Gallus.
OX NCBI_TaxID=9031;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], AND DEVELOPMENTAL STAGE.
RX PubMed=10842055; DOI=10.1016/s0925-4773(00)00321-x;
RA Ataliotis P.;
RT "Platelet-derived growth factor A modulates limb chondrogenesis both in
RT vivo and in vitro.";
RL Mech. Dev. 94:13-24(2000).
RN [2]
RP FUNCTION.
RX PubMed=18192285; DOI=10.1242/dev.013763;
RA Pickett E.A., Olsen G.S., Tallquist M.D.;
RT "Disruption of PDGFRalpha-initiated PI3K activation and migration of somite
RT derivatives leads to spina bifida.";
RL Development 135:589-598(2008).
CC -!- FUNCTION: Tyrosine-protein kinase that acts as 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, ECO:0000269|PubMed:18192285}.
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|UniProtKB:P16234};
CC Single-pass type I membrane protein {ECO:0000250|UniProtKB:P16234}.
CC Cell projection, cilium {ECO:0000250|UniProtKB:P26618}. Golgi apparatus
CC {ECO:0000250|UniProtKB:P26618}.
CC -!- DEVELOPMENTAL STAGE: Expressed throughout the mesenchyme of early limb
CC buds. At later stages, present in the condensing chondrogenic
CC mesenchyme, then the perichondrium. Down-regulated in areas that will
CC not give rise to cartilage and is then lost from cartilage forming
CC areas after they begin to differentiate. {ECO:0000269|PubMed:10842055}.
CC -!- PTM: Ubiquitinated, leading to its internalization and degradation.
CC {ECO:0000250|UniProtKB:P26618}.
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}.
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DR EMBL; AF188842; AAF01460.1; -; mRNA.
DR AlphaFoldDB; Q9PUF6; -.
DR SMR; Q9PUF6; -.
DR STRING; 9031.ENSGALP00000009175; -.
DR PaxDb; Q9PUF6; -.
DR VEuPathDB; HostDB:geneid_395509; -.
DR eggNOG; KOG0200; Eukaryota.
DR InParanoid; Q9PUF6; -.
DR PhylomeDB; Q9PUF6; -.
DR Proteomes; UP000000539; Unplaced.
DR GO; GO:0005929; C:cilium; ISS:UniProtKB.
DR GO; GO:0005794; C:Golgi apparatus; ISS:UniProtKB.
DR GO; GO:0005887; C:integral component of plasma membrane; IBA:GO_Central.
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:0005018; F:platelet-derived growth factor alpha-receptor activity; IBA:GO_Central.
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:0006935; P:chemotaxis; IEA:UniProtKB-KW.
DR GO; GO:0048701; P:embryonic cranial skeleton morphogenesis; IBA:GO_Central.
DR GO; GO:0048704; P:embryonic skeletal system morphogenesis; IMP:UniProtKB.
DR GO; GO:0033674; P:positive regulation of kinase activity; IBA:GO_Central.
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; 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; 1.
DR Pfam; PF07714; PK_Tyr_Ser-Thr; 1.
DR PIRSF; PIRSF500950; Alpha-PDGF_receptor; 1.
DR SMART; SM00409; IG; 4.
DR SMART; SM00408; IGc2; 2.
DR SMART; SM00219; TyrKc; 1.
DR SUPFAM; SSF48726; SSF48726; 4.
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; Cell projection; Chemotaxis;
KW Developmental protein; Disulfide bond; Glycoprotein; Golgi apparatus;
KW Immunoglobulin domain; Kinase; Membrane; Nucleotide-binding;
KW Phosphoprotein; Receptor; Reference proteome; Repeat; Signal; Transferase;
KW Transmembrane; Transmembrane helix; Tyrosine-protein kinase;
KW Ubl conjugation.
FT SIGNAL 1..23
FT /evidence="ECO:0000255"
FT CHAIN 24..1087
FT /note="Platelet-derived growth factor receptor alpha"
FT /id="PRO_0000248883"
FT TOPO_DOM 24..528
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 529..549
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 550..1087
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 26..104
FT /note="Ig-like C2-type 1"
FT DOMAIN 116..208
FT /note="Ig-like C2-type 2"
FT DOMAIN 213..312
FT /note="Ig-like C2-type 3"
FT DOMAIN 314..411
FT /note="Ig-like C2-type 4"
FT DOMAIN 414..517
FT /note="Ig-like C2-type 5"
FT DOMAIN 593..954
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT REGION 1000..1059
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1027..1042
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1043..1058
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 818
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT ECO:0000255|PROSITE-ProRule:PRU10028"
FT BINDING 599..607
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 627
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT MOD_RES 572
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000250"
FT MOD_RES 574
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000250"
FT MOD_RES 720
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 742
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000250"
FT MOD_RES 754
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000250"
FT MOD_RES 762
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000250"
FT MOD_RES 768
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000250"
FT MOD_RES 849
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000250"
FT MOD_RES 988
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000250"
FT MOD_RES 1017
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000250"
FT CARBOHYD 44
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 75
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 88
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 102
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 353
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 359
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 458
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 468
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 49..99
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
FT DISULFID 149..189
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
FT DISULFID 235..290
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
FT DISULFID 435..501
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
SQ SEQUENCE 1087 AA; 122941 MW; F3306BDD3D983E31 CRC64;
MGTPPRTFLI LGCFLTGPLL TLCQLPLPTI VPNRNEMVVQ LNSNFTLKCS GDSEVSWQYP
VTEGSHRIDI RHEENNSGLF VTVLEVGNAS AAHTGMYVCY YNHTQVEDGE VEGKDIYIYV
PDPDMPFVPS LPEDQFILVE EGDPTVIPCR TSDPSAEVTL VNSLDKPVYA FYDSKQGFVG
NFLAGPYTCK TMVKGVEFKS DEFLIYILRA TSQLPVEIEA LKTVYKTGET IVVTCVVFDN
EVVNLQWNYP GKVKEKGLIK LDDIKVPSQK LVYMLTIPDV LVKDTGDYEC TARHATKEVK
ENKKVVITVH DKGFIHLEPQ FSPLEAVNLH EVKNFVVDVQ AYPAPKMYWL KDNVTLIENL
TEIVTSSNRV QETRFQSVLK LIRAKEEDSG TILWLLKNED EIKRYTFSLL IQVPALILDL
MDDHQGSAGR QTVRCLAEGT PLPDVEWLVC KDIKKCSNDT SWTLLTNNIS DIHMEAHLDE
RNMVESQVTF QKVEETLAVR CVARNDLGAV TRELKLVAPT LRSELTVAAA VLVLLVIVII
SLIVLVIIWK QKPRYEIRWR VIESISPDGH EYIYVDPMQL PYDSRWEFPR DGLVLGRILG
SGAFGKVVEG TAYGLSRSQP VMKVAVKMLK PTARSSEKQA LMSELKIMTH LGPHLNIVNL
LGACTKSGPI YIITEYCFYG DLVNYLHKNR DNFLSRHPEK PKKDLDIFGM NPADESTRSY
VILSFENTGE YMDMKQADTT QYVPMLERKE GSKYSDIQRS VYDRPASYKK KSLSESEVKN
LLSDDGSEGL SLLDLLSFTY QVARGMEFLA SKNCVHRDLA ARNVLLAQGK IVKICDFGLA
RDIMHDSNYV SKGSTFLPVK WMAPESIFDN LYTTLSDVWS YGILLWEIFS LGGILYPGMM
VDSTFYNKIK SGYRMAKPDH ATNEVYEIMV KCWNNEPEKR PSFYHLSEIV ESLLPGEYKK
SYEKIHLDFL KSDHPAVTRM RGDCDNAYIG VTYKNEDKIK DRESGFDEQR LSADSGYITP
LPDIDPVSED ELGKRNRHSS QTSEESAIET GSSSSTFIKR EDETIEDIDM MDDIGIDSSD
LVEDSFL
