ID   PGFRA_XENLA             Reviewed;        1087 AA.
AC   P26619;
DT   01-AUG-1992, integrated into UniProtKB/Swiss-Prot.
DT   01-AUG-1992, sequence version 1.
DT   27-MAR-2024, entry version 144.
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   Xenopus laevis (African clawed frog).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Amphibia;
OC   Batrachia; Anura; Pipoidea; Pipidae; Xenopodinae; Xenopus; Xenopus.
OX   NCBI_TaxID=8355;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RX   PubMed=8358864; DOI=10.1002/dvg.1020140305;
RA   Jones S.D., Ho L., Smith J.C., Yordan C., Stiles C.D., Mercola M.;
RT   "The Xenopus platelet-derived growth factor alpha receptor: cDNA cloning
RT   and demonstration that mesoderm induction establishes the lineage-specific
RT   pattern of ligand and receptor gene expression.";
RL   Dev. Genet. 14:185-193(1993).
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|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   -!- 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; M80798; AAA49929.1; -; mRNA.
DR   PIR; I51552; I51552.
DR   AlphaFoldDB; P26619; -.
DR   SMR; P26619; -.
DR   GlyCosmos; P26619; 9 sites, No reported glycans.
DR   MaxQB; P26619; -.
DR   AGR; Xenbase:XB-GENE-6072934; -.
DR   Xenbase; XB-GENE-6072934; pdgfra.L.
DR   BRENDA; 2.7.10.1; 6725.
DR   Proteomes; UP000186698; Genome assembly.
DR   GO; GO:0005929; C:cilium; ISS:UniProtKB.
DR   GO; GO:0005794; C:Golgi apparatus; ISS:UniProtKB.
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   GO; GO:0016310; P:phosphorylation; IEA:UniProtKB-KW.
DR   CDD; cd05859; Ig4_PDGFR; 1.
DR   CDD; cd05861; IgI_PDGFR-alphabeta; 1.
DR   CDD; cd05105; PTKc_PDGFR_alpha; 1.
DR   Gene3D; 2.60.40.10; Immunoglobulins; 5.
DR   Gene3D; 1.10.510.10; Transferase(Phosphotransferase) domain 1; 1.
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   PANTHER; PTHR24416:SF52; PLATELET-DERIVED GROWTH FACTOR RECEPTOR ALPHA; 1.
DR   PANTHER; PTHR24416; TYROSINE-PROTEIN KINASE RECEPTOR; 1.
DR   Pfam; PF07679; I-set; 2.
DR   Pfam; PF07714; PK_Tyr_Ser-Thr; 1.
DR   PIRSF; PIRSF500950; Alpha-PDGF_receptor; 1.
DR   PIRSF; PIRSF000615; TyrPK_CSF1-R; 1.
DR   PRINTS; PR01832; VEGFRECEPTOR.
DR   SMART; SM00409; IG; 3.
DR   SMART; SM00408; IGc2; 3.
DR   SMART; SM00220; S_TKc; 1.
DR   SMART; SM00219; TyrKc; 1.
DR   SUPFAM; SSF48726; Immunoglobulin; 3.
DR   SUPFAM; SSF56112; Protein kinase-like (PK-like); 1.
DR   PROSITE; PS50835; IG_LIKE; 3.
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..24
FT                   /evidence="ECO:0000255"
FT   CHAIN           25..1087
FT                   /note="Platelet-derived growth factor receptor alpha"
FT                   /id="PRO_0000016763"
FT   TOPO_DOM        25..530
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        531..551
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        552..1087
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   DOMAIN          27..114
FT                   /note="Ig-like C2-type 1"
FT   DOMAIN          118..211
FT                   /note="Ig-like C2-type 2"
FT   DOMAIN          217..309
FT                   /note="Ig-like C2-type 3"
FT   DOMAIN          315..409
FT                   /note="Ig-like C2-type 4"
FT   DOMAIN          417..519
FT                   /note="Ig-like C2-type 5"
FT   DOMAIN          595..970
FT                   /note="Protein kinase"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT   REGION          1017..1064
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         601..609
FT                   /ligand="ATP"
FT                   /ligand_id="ChEBI:CHEBI:30616"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT   BINDING         629
FT                   /ligand="ATP"
FT                   /ligand_id="ChEBI:CHEBI:30616"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT   MOD_RES         574
FT                   /note="Phosphotyrosine; by autocatalysis"
FT                   /evidence="ECO:0000250"
FT   MOD_RES         576
FT                   /note="Phosphotyrosine; by autocatalysis"
FT                   /evidence="ECO:0000250"
FT   MOD_RES         722
FT                   /note="Phosphotyrosine; by autocatalysis"
FT                   /evidence="ECO:0000250"
FT   MOD_RES         733
FT                   /note="Phosphotyrosine; by autocatalysis"
FT                   /evidence="ECO:0000250"
FT   MOD_RES         744
FT                   /note="Phosphotyrosine; by autocatalysis"
FT                   /evidence="ECO:0000250"
FT   MOD_RES         756
FT                   /note="Phosphotyrosine; by autocatalysis"
FT                   /evidence="ECO:0000250"
FT   MOD_RES         764
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        77
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        104
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        216
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        282
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        309
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        356
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        362
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        461
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        471
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   DISULFID        50..101
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
FT   DISULFID        151..192
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
FT   DISULFID        238..293
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
FT   DISULFID        438..503
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
SQ   SEQUENCE   1087 AA;  122699 MW;  A621E6B0A5BADCA6 CRC64;
     MMPAMRASLI LGCLLIIGPW AILAENPLPT IFPDKDELVQ ALHSSFTLKC TGESEVSWQN
     PNSNPEKQNV VIRSEENNSG LFVSILEVSD ASAFDTGLYT CYHNHTQTEE SEIEGTDIYI
     YVPDPNVPFA PPGLFDHIIV VEEDESALVP CRTTDPSSEV TLKNIESSRT VFAFYDSKQG
     FAGNFPPGSY ICETTSNKMV YQTEPYILQT WKATHNISVE MEAPKTMFRA GETIAIDCIV
     LDNEVVDLKW TYPGKQRGVG IRNVEESKVP YQRLVYTLTL ANATTEDSGE YECAVIHATL
     DNRVVKKTNI TVHEKGFIDL EPMFGSEEFA NLHEVKSFIV NLHAYPTPGL FWLKDNRTLS
     ENLTEITTSI VTTKETRFQS KLKLIRAKEE DSGLYTLVAQ NDRETKSYSF ILQIKVPALI
     LELVDKHHGA SGEQTVGCLA KGMPVPDVEW LVCKDIKRCN NDTLWSILAT NGSEISMETH
     QDDEQIESQV TFKKIEETMA IRCIAKNELG VVARELKLVA PTLRSELTVA AAVLVLLVIV
     IISLIVLVII WKQKPRYEIR WRVIESISPD GHEYIYVDPM QLPYDSRWEF PRDGLVLGRI
     LGSGAFGKVV EGAAYGLSRS QPVMKVAVKM LKPTARSSEK QALMSELKIM THLGAHLNIV
     NLLGACTKSG PIYIITEYCF YGDLVNYLHK NRDNFQSRHP EKPKKDLDIF GLNPADESTR
     SYVILSFENN GDYMDMKQAD TMQYVPMLEM KEPSKYSDIQ RSLYDRPASY KKKPLSEVKN
     ILSDDGFEGL TVLDLLSFTY QVARGMEFLA SKNCVHRDLA ARNVLLAHGK IVKICDFGLA
     RDIMHDSNYV SKGSTFLPVK WMAPESIFDN LYTTLSDVWS FGILLWEIFS LGGTPYPGMI
     VDSTFYNKIK SGYRMAKPDH ATHEVYDIMV KCWNSEPEKR PSFRHLSDIV ESLLPMEYKR
     CYETVLHDFL KSDHPAVTRM RSDSDNSYIG VTYKNEHKMK DRESGFDEQR LSADSGYIIP
     LPDIDPVSED ESGKRNRHSS QTSEESAIET GSSSSTFIKR DDETIEDIDM MDDIGIDSSD
     LVEDSFL
//