PDGFA_RAT
ID PDGFA_RAT Reviewed; 204 AA.
AC P28576;
DT 01-DEC-1992, integrated into UniProtKB/Swiss-Prot.
DT 01-FEB-1994, sequence version 2.
DT 03-AUG-2022, entry version 164.
DE RecName: Full=Platelet-derived growth factor subunit A;
DE Short=PDGF subunit A;
DE AltName: Full=PDGF-1;
DE AltName: Full=Platelet-derived growth factor A chain;
DE AltName: Full=Platelet-derived growth factor alpha polypeptide;
DE Flags: Precursor;
GN Name=Pdgfa; Synonyms=Rpa1;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 8-204.
RX PubMed=8318539; DOI=10.1016/0167-4781(93)90127-y;
RA Herren B., Weyer K.A., Rouge M., Loetscher P., Pech M.;
RT "Conservation in sequence and affinity of human and rodent PDGF ligands and
RT receptors.";
RL Biochim. Biophys. Acta 1173:294-302(1993).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=8447423; DOI=10.1152/ajplung.1993.264.2.l100;
RA Katayose D., Ohe M., Yamauchi K., Ogata M., Shirato K., Fujita H.,
RA Shibahara S., Takishima T.;
RT "Increased expression of PDGF A- and B-chain genes in rat lungs with
RT hypoxic pulmonary hypertension.";
RL Am. J. Physiol. 264:L100-L106(1993).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM SHORT).
RA Xia Y., Feng L., Tang W.W., Wilson C.B.;
RT "Cloning and expression of rat platelet-derived growth factor A-chain.";
RL J. Am. Soc. Nephrol. 3:622-622(1992).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 58-196 (ISOFORM SHORT).
RC STRAIN=Fischer 344; TISSUE=Smooth muscle;
RX PubMed=8469035; DOI=10.1016/0047-6374(93)90113-6;
RA Szabo P., Weksler D., Whittington E., Weksler B.B.;
RT "The age-dependent proliferation of rat aortic smooth muscle cells is
RT independent of differential splicing of PDGF A-chain mRNA.";
RL Mech. Ageing Dev. 67:79-89(1993).
CC -!- FUNCTION: Growth factor that plays an essential role in the regulation
CC of embryonic development, cell proliferation, cell migration, survival
CC and chemotaxis. Potent mitogen for cells of mesenchymal origin.
CC Required for normal lung alveolar septum formation during
CC embryogenesis, normal development of the gastrointestinal tract, normal
CC development of Leydig cells and spermatogenesis. Required for normal
CC oligodendrocyte development and normal myelination in the spinal cord
CC and cerebellum. Plays an important role in wound healing. Signaling is
CC modulated by the formation of heterodimers with PDGFB (By similarity).
CC {ECO:0000250}.
CC -!- SUBUNIT: Homodimer; antiparallel disulfide-linked dimer. Heterodimer
CC with PDGFB; antiparallel disulfide-linked dimer. The PDGFA homodimer
CC interacts with PDGFRA homodimers, and with heterodimers formed by
CC PDGFRA and PDGFRB. The heterodimer composed of PDGFA and PDGFB
CC interacts with PDGFRA homodimers, and with heterodimers formed by
CC PDGFRA and PDGFRB. Interacts with CSPG4 (By similarity). {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: Secreted. Note=Released by platelets upon
CC wounding. {ECO:0000250}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=Long;
CC IsoId=P28576-1; Sequence=Displayed;
CC Name=Short;
CC IsoId=P28576-2; Sequence=VSP_004609, VSP_004610;
CC -!- DEVELOPMENTAL STAGE: In kidney epithelial tissues, the shorter form
CC predominates in young (1 day old) rats while the longer form becomes
CC more prevalant during aging.
CC -!- DOMAIN: The long form contains a basic insert which acts as a cell
CC retention signal.
CC -!- SIMILARITY: Belongs to the PDGF/VEGF growth factor family.
CC {ECO:0000305}.
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DR EMBL; L06894; AAB59693.1; -; mRNA.
DR EMBL; Z14120; CAA78490.1; -; mRNA.
DR EMBL; D10106; BAA00987.1; -; mRNA.
DR EMBL; L06238; AAA41932.1; -; mRNA.
DR EMBL; S57864; AAB26134.2; -; mRNA.
DR PIR; A48851; A48851.
DR PIR; S25096; S25096.
DR RefSeq; NP_036933.1; NM_012801.1. [P28576-2]
DR AlphaFoldDB; P28576; -.
DR SMR; P28576; -.
DR ComplexPortal; CPX-6591; Platelet-derived growth factor AB complex.
DR STRING; 10116.ENSRNOP00000001775; -.
DR BindingDB; P28576; -.
DR GlyGen; P28576; 1 site.
DR PaxDb; P28576; -.
DR DNASU; 25266; -.
DR Ensembl; ENSRNOT00000042117; ENSRNOP00000040116; ENSRNOG00000001312. [P28576-2]
DR GeneID; 25266; -.
DR KEGG; rno:25266; -.
DR UCSC; RGD:3282; rat. [P28576-1]
DR CTD; 5154; -.
DR RGD; 3282; Pdgfa.
DR VEuPathDB; HostDB:ENSRNOG00000001312; -.
DR eggNOG; ENOG502QVAU; Eukaryota.
DR GeneTree; ENSGT00940000159039; -.
DR InParanoid; P28576; -.
DR PhylomeDB; P28576; -.
DR Reactome; R-RNO-114608; Platelet degranulation.
DR Reactome; R-RNO-1257604; PIP3 activates AKT signaling.
DR Reactome; R-RNO-186763; Downstream signal transduction.
DR Reactome; R-RNO-186797; Signaling by PDGF.
DR Reactome; R-RNO-3000171; Non-integrin membrane-ECM interactions.
DR Reactome; R-RNO-5673001; RAF/MAP kinase cascade.
DR Reactome; R-RNO-6811558; PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling.
DR PRO; PR:P28576; -.
DR Proteomes; UP000002494; Chromosome 12.
DR Bgee; ENSRNOG00000001312; Expressed in pancreas and 19 other tissues.
DR ExpressionAtlas; P28576; baseline and differential.
DR Genevisible; P28576; RN.
DR GO; GO:0009986; C:cell surface; ISS:UniProtKB.
DR GO; GO:0005615; C:extracellular space; ISS:UniProtKB.
DR GO; GO:0016020; C:membrane; IEA:InterPro.
DR GO; GO:0005902; C:microvillus; ISS:UniProtKB.
DR GO; GO:1990265; C:platelet-derived growth factor complex; ISO:RGD.
DR GO; GO:0005518; F:collagen binding; ISS:UniProtKB.
DR GO; GO:0008083; F:growth factor activity; ISS:UniProtKB.
DR GO; GO:0070851; F:growth factor receptor binding; IBA:GO_Central.
DR GO; GO:0048407; F:platelet-derived growth factor binding; ISO:RGD.
DR GO; GO:0005161; F:platelet-derived growth factor receptor binding; ISS:UniProtKB.
DR GO; GO:0046982; F:protein heterodimerization activity; ISO:RGD.
DR GO; GO:0042803; F:protein homodimerization activity; ISS:UniProtKB.
DR GO; GO:0030036; P:actin cytoskeleton organization; ISS:UniProtKB.
DR GO; GO:0001525; P:angiogenesis; ISS:UniProtKB.
DR GO; GO:0009887; P:animal organ morphogenesis; ISS:UniProtKB.
DR GO; GO:0060348; P:bone development; ISO:RGD.
DR GO; GO:0030031; P:cell projection assembly; ISS:UniProtKB.
DR GO; GO:0071560; P:cellular response to transforming growth factor beta stimulus; IEP:RGD.
DR GO; GO:0048565; P:digestive tract development; ISO:RGD.
DR GO; GO:1990401; P:embryonic lung development; ISO:RGD.
DR GO; GO:0001942; P:hair follicle development; ISS:UniProtKB.
DR GO; GO:0048839; P:inner ear development; IEP:RGD.
DR GO; GO:0048286; P:lung alveolus development; ISS:UniProtKB.
DR GO; GO:0008584; P:male gonad development; IEP:RGD.
DR GO; GO:0050919; P:negative chemotaxis; ISS:UniProtKB.
DR GO; GO:0010512; P:negative regulation of phosphatidylinositol biosynthetic process; ISS:UniProtKB.
DR GO; GO:0010544; P:negative regulation of platelet activation; ISS:UniProtKB.
DR GO; GO:0048008; P:platelet-derived growth factor receptor signaling pathway; ISS:UniProtKB.
DR GO; GO:0051781; P:positive regulation of cell division; IEA:UniProtKB-KW.
DR GO; GO:0030335; P:positive regulation of cell migration; ISS:UniProtKB.
DR GO; GO:0008284; P:positive regulation of cell population proliferation; IMP:RGD.
DR GO; GO:0070374; P:positive regulation of ERK1 and ERK2 cascade; ISS:UniProtKB.
DR GO; GO:0048146; P:positive regulation of fibroblast proliferation; ISS:UniProtKB.
DR GO; GO:0043406; P:positive regulation of MAP kinase activity; ISS:UniProtKB.
DR GO; GO:0043410; P:positive regulation of MAPK cascade; ISS:UniProtKB.
DR GO; GO:0002053; P:positive regulation of mesenchymal cell proliferation; ISS:UniProtKB.
DR GO; GO:0035793; P:positive regulation of metanephric mesenchymal cell migration by platelet-derived growth factor receptor-beta signaling pathway; ISS:UniProtKB.
DR GO; GO:0014068; P:positive regulation of phosphatidylinositol 3-kinase signaling; ISS:UniProtKB.
DR GO; GO:0031954; P:positive regulation of protein autophosphorylation; ISS:UniProtKB.
DR GO; GO:0051897; P:positive regulation of protein kinase B signaling; ISS:UniProtKB.
DR GO; GO:0060683; P:regulation of branching involved in salivary gland morphogenesis by epithelial-mesenchymal signaling; ISS:UniProtKB.
DR GO; GO:0050730; P:regulation of peptidyl-tyrosine phosphorylation; ISS:UniProtKB.
DR GO; GO:0014910; P:regulation of smooth muscle cell migration; ISS:UniProtKB.
DR GO; GO:0032355; P:response to estradiol; IEP:RGD.
DR GO; GO:0001666; P:response to hypoxia; IEP:RGD.
DR GO; GO:0010035; P:response to inorganic substance; IEP:RGD.
DR GO; GO:0010033; P:response to organic substance; IEP:RGD.
DR GO; GO:0032526; P:response to retinoic acid; IEP:RGD.
DR GO; GO:0009611; P:response to wounding; ISS:UniProtKB.
DR GO; GO:0009410; P:response to xenobiotic stimulus; IEP:RGD.
DR GO; GO:0043588; P:skin development; ISS:UniProtKB.
DR GO; GO:0042060; P:wound healing; IEP:RGD.
DR CDD; cd00135; PDGF; 1.
DR Gene3D; 2.10.90.10; -; 1.
DR InterPro; IPR029034; Cystine-knot_cytokine.
DR InterPro; IPR023581; PD_growth_factor_CS.
DR InterPro; IPR000072; PDGF/VEGF_dom.
DR InterPro; IPR006782; PDGF_N.
DR Pfam; PF00341; PDGF; 1.
DR Pfam; PF04692; PDGF_N; 1.
DR SMART; SM00141; PDGF; 1.
DR SUPFAM; SSF57501; SSF57501; 1.
DR PROSITE; PS00249; PDGF_1; 1.
DR PROSITE; PS50278; PDGF_2; 1.
PE 2: Evidence at transcript level;
KW Alternative splicing; Cleavage on pair of basic residues;
KW Developmental protein; Disulfide bond; Glycoprotein; Growth factor;
KW Mitogen; Reference proteome; Secreted; Signal.
FT SIGNAL 1..20
FT /evidence="ECO:0000250"
FT PROPEP 21..85
FT /note="Removed in mature form"
FT /id="PRO_0000023362"
FT CHAIN 86..204
FT /note="Platelet-derived growth factor subunit A"
FT /id="PRO_0000023363"
FT REGION 158..162
FT /note="Receptor binding site"
FT /evidence="ECO:0000255"
FT CARBOHYD 134
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 96..140
FT /evidence="ECO:0000250"
FT DISULFID 123
FT /note="Interchain"
FT /evidence="ECO:0000250"
FT DISULFID 129..177
FT /evidence="ECO:0000250"
FT DISULFID 132
FT /note="Interchain"
FT /evidence="ECO:0000250"
FT DISULFID 133..179
FT /evidence="ECO:0000250"
FT VAR_SEQ 194..196
FT /note="GRR -> DVR (in isoform Short)"
FT /evidence="ECO:0000303|PubMed:8469035, ECO:0000303|Ref.3"
FT /id="VSP_004609"
FT VAR_SEQ 197..204
FT /note="Missing (in isoform Short)"
FT /evidence="ECO:0000303|PubMed:8469035, ECO:0000303|Ref.3"
FT /id="VSP_004610"
FT CONFLICT 85..111
FT /note="KRSIEEAIPAVCKTRTVIYEIPRSQVD -> REVLRKPFPQFARPGRSFTRY
FT LGARWT (in Ref. 2; BAA00987)"
FT /evidence="ECO:0000305"
FT CONFLICT 119
FT /note="I -> T (in Ref. 3; AAA41932)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 204 AA; 23307 MW; FA413F74E86F742C CRC64;
MRTWACLLLL GCGYLAHALA EEAEIPRELI ERLARSQIHS IRDLQRLLEI DSVGAEDALE
TNLRAHGSHT VKHVPEKRPV PIRRKRSIEE AIPAVCKTRT VIYEIPRSQV DPTSANFLIW
PPCVEVKRCT GCCNTSSVKC QPSRVHHRSV KVAKVEYVRK KPKLKEVQVR LEEHLECACA
TSNLNPDHRE EETGRRRESG KKRK
