PGFRA_XENLA
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 03-AUG-2022, entry version 139.
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 MaxQB; P26619; -.
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: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; SM00220; S_TKc; 1.
DR SMART; SM00219; TyrKc; 1.
DR SUPFAM; SSF48726; SSF48726; 3.
DR SUPFAM; SSF56112; SSF56112; 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
