PGFRA_DANRE
ID PGFRA_DANRE Reviewed; 1059 AA.
AC Q9DE49;
DT 05-SEP-2006, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2001, sequence version 1.
DT 03-AUG-2022, entry version 138.
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;
GN Name=pdgfra;
OS Danio rerio (Zebrafish) (Brachydanio rerio).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Actinopterygii; Neopterygii; Teleostei; Ostariophysi; Cypriniformes;
OC Danionidae; Danioninae; Danio.
OX NCBI_TaxID=7955;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], AND DEVELOPMENTAL STAGE.
RX PubMed=12211169; DOI=10.1007/s00427-002-0234-3;
RA Liu L., Korzh V., Balasubramaniyan N.V., Ekker M., Ge R.;
RT "Platelet-derived growth factor A (pdgf-a) expression during zebrafish
RT embryonic development.";
RL Dev. Genes Evol. 212:298-301(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|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: Highly expressed in fertilized eggs as well as in
CC all embryonic cells up to the end of gastrulation. Spatially restricted
CC expression started after the onset of segmentation and was mainly
CC localized in the developing pharyngeal arches. Transient expression was
CC also detected in Kupffer's vesicle, a teleost-specific structure, and
CC in lateral trunk and tail regions surrounding the neural keel, as well
CC as areas of the developing pronephros. {ECO:0000269|PubMed:12211169}.
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; AF200951; AAG43479.1; -; mRNA.
DR RefSeq; NP_571534.1; NM_131459.2.
DR AlphaFoldDB; Q9DE49; -.
DR SMR; Q9DE49; -.
DR STRING; 7955.ENSDARP00000094286; -.
DR PaxDb; Q9DE49; -.
DR PRIDE; Q9DE49; -.
DR GeneID; 386856; -.
DR KEGG; dre:386856; -.
DR CTD; 5156; -.
DR ZFIN; ZDB-GENE-990415-208; pdgfra.
DR eggNOG; KOG0200; Eukaryota.
DR InParanoid; Q9DE49; -.
DR OrthoDB; 236292at2759; -.
DR Reactome; R-DRE-1257604; PIP3 activates AKT signaling.
DR Reactome; R-DRE-186763; Downstream signal transduction.
DR Reactome; R-DRE-186797; Signaling by PDGF.
DR Reactome; R-DRE-5673001; RAF/MAP kinase cascade.
DR Reactome; R-DRE-6811558; PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling.
DR PRO; PR:Q9DE49; -.
DR Proteomes; UP000000437; Genome assembly.
DR Proteomes; UP000814640; 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:0003261; P:cardiac muscle progenitor cell migration to the midline involved in heart field formation; IMP:ZFIN.
DR GO; GO:0003317; P:cardioblast cell midline fusion; IMP:ZFIN.
DR GO; GO:0061300; P:cerebellum vasculature development; IGI:ZFIN.
DR GO; GO:0006935; P:chemotaxis; IEA:UniProtKB-KW.
DR GO; GO:0048701; P:embryonic cranial skeleton morphogenesis; IMP:ZFIN.
DR GO; GO:0048702; P:embryonic neurocranium morphogenesis; IMP:ZFIN.
DR GO; GO:0007507; P:heart development; IMP:ZFIN.
DR GO; GO:0001755; P:neural crest cell migration; IMP:ZFIN.
DR GO; GO:0033674; P:positive regulation of kinase activity; IBA:GO_Central.
DR GO; GO:1901532; P:regulation of hematopoietic progenitor cell differentiation; IGI:ZFIN.
DR GO; GO:0060021; P:roof of mouth development; IMP:ZFIN.
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; 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; 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; Transferase;
KW Transmembrane; Transmembrane helix; Tyrosine-protein kinase;
KW Ubl conjugation.
FT CHAIN 1..1059
FT /note="Platelet-derived growth factor receptor alpha"
FT /id="PRO_0000248884"
FT TOPO_DOM 1..503
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 504..524
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 525..1059
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 32..91
FT /note="Ig-like C2-type 1"
FT DOMAIN 103..180
FT /note="Ig-like C2-type 2"
FT DOMAIN 189..282
FT /note="Ig-like C2-type 3"
FT DOMAIN 293..380
FT /note="Ig-like C2-type 4"
FT DOMAIN 389..477
FT /note="Ig-like C2-type 5"
FT DOMAIN 568..942
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT REGION 975..1036
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1001..1015
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1016..1031
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 790
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT ECO:0000255|PROSITE-ProRule:PRU10028"
FT BINDING 574..582
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 602
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT MOD_RES 547
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000250"
FT MOD_RES 549
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000250"
FT MOD_RES 695
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000250"
FT MOD_RES 706
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000250"
FT MOD_RES 717
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000250"
FT MOD_RES 729
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000250"
FT MOD_RES 737
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000250"
FT MOD_RES 821
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000250"
FT MOD_RES 961
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000250"
FT MOD_RES 990
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000250"
FT CARBOHYD 67
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 84
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 272
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 365
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 432
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 443
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 33..78
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
FT DISULFID 123..164
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
FT DISULFID 210..264
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
FT DISULFID 409..476
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
SQ SEQUENCE 1059 AA; 118211 MW; 0AE93E2ABD9A72F3 CRC64;
MFPVLPQSVQ APLIWPQRES MEVSLHSTFR LTCRGQTELS WNGPVFIDDQ TNSVKKGLFI
STVTISNATA VHTGEYVCSS EPFNSTESTI YIYVPDPQTP FVPSMTPFEN HVLTSYDEME
IPCRVTDPSA SVSLIHMGTD QVMPSAYDSK RGFIGLFGAG TYVCRALIHG QNHDSIEYIV
HGWTGGSDLR VELRAVKRTL LVGETITVDC VAKGSEVLED HWKYPGKLAN RGPKTVKENK
LNLEIYYTLT VTNASPKDSG IYACSITDIM SNESQTKELT ITVYDHEFVH INPLIGPVET
ARLDEVPEFK VDIESFPAPK VTWLKDSSVL GDDTAEISTT LLKIGETSYQ GVLNLIRAKA
EDSGNYTVKA EIGSISTSYS FYLQVKVPPV IVDLIDVHHG SAAGQEVVCT AGGSPFPEVD
WDICKNLKHC ANDSSQWMPL PINSTDITVE LQMNVDNHIE SHIIFHHLEG TVAVRCLARN
DMGVVSREVK LMSSGPHSEL TVAAAVLVLL VIVIISLIVL VIIWKQKPRY EIRWRVIESV
SPDGHEYIYV DPMQLPYDSR WEFPRDGLVL GRVLGSGAFG KVVEGTAYGL SRSQPVMKVA
VKMLKPTARS SEKQALMSEL KIMTHLGPHL NIVNLLGACT KSGPIYIITE YCFYGDLVNY
LHKNRDGFLS RHTEKGKKDL DIFGINPADE SSRSYVILSL EGKGDYMDMK QADTMQYVPM
LEMNEASKYS PIQRSDYDHP PSHRQFNDEA ESLLSDDSAE GLTTMDLLSF TYQVARGMEF
LASKNCVHRD LAARNVLLSQ GKIVKICDFG LARDIMHDNN YVSKGSTFLP VKWMAPESIF
DNLYTTLSDV WSYGILLWEI FSLGGTPYPG MVVDSSFYNK IKSGYRMTKP EHASSDVYEL
MMKCWNSEPE KRPSFHSLSD TVASLLPSGF KRCYERVNHD FLKSDHPAVT RVQCIDNDDA
YMGVLYKNQG KMKTRESGFD EQRLSSDSGY IIPLPDLDPL SNEDYSKRNR HSSQTSEESA
IDTGSSSSTT KREGETLEDI TLLDEMCLDS GDLVEDSFL
