PDGFA_MOUSE
ID PDGFA_MOUSE Reviewed; 211 AA.
AC P20033;
DT 01-FEB-1991, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-1996, sequence version 2.
DT 03-AUG-2022, entry version 173.
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;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORMS LONG AND SHORT).
RC STRAIN=BALB/cJ;
RX PubMed=1340209; DOI=10.3109/08977199209021542;
RA Rorsman F., Betsholtz C.;
RT "Characterization of the mouse PDGF A-chain gene. Evolutionary conservation
RT of gene structure, nucleotide sequence and alternative splicing.";
RL Growth Factors 6:303-313(1992).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM SHORT).
RC STRAIN=F9;
RX PubMed=2155144; DOI=10.1016/0012-1606(90)90181-h;
RA Mercola M., Wang C., Kelly J., Brownlee C., Jackson-Grusby L., Stiles C.,
RA Bowen-Pope D.F.;
RT "Selective expression of PDGF A and its receptor during early mouse
RT embryogenesis.";
RL Dev. Biol. 138:114-122(1990).
RN [3]
RP DISRUPTION PHENOTYPE, AND FUNCTION.
RX PubMed=8681381; DOI=10.1016/s0092-8674(00)81270-2;
RA Bostrom H., Willetts K., Pekny M., Leveen P., Lindahl P., Hedstrand H.,
RA Pekna M., Hellstrom M., Gebre-Medhin S., Schalling M., Nilsson M.,
RA Kurland S., Tornell J., Heath J.K., Betsholtz C.;
RT "PDGF-A signaling is a critical event in lung alveolar myofibroblast
RT development and alveogenesis.";
RL Cell 85:863-873(1996).
RN [4]
RP DISRUPTION PHENOTYPE, AND FUNCTION.
RX PubMed=9374392; DOI=10.1242/dev.124.20.3943;
RA Lindahl P., Karlsson L., Hellstrom M., Gebre-Medhin S., Willetts K.,
RA Heath J.K., Betsholtz C.;
RT "Alveogenesis failure in PDGF-A-deficient mice is coupled to lack of distal
RT spreading of alveolar smooth muscle cell progenitors during lung
RT development.";
RL Development 124:3943-3953(1997).
RN [5]
RP DISRUPTION PHENOTYPE, AND FUNCTION.
RX PubMed=9876175; DOI=10.1242/dev.126.3.457;
RA Fruttiger M., Karlsson L., Hall A.C., Abramsson A., Calver A.R.,
RA Bostrom H., Willetts K., Bertold C.H., Heath J.K., Betsholtz C.,
RA Richardson W.D.;
RT "Defective oligodendrocyte development and severe hypomyelination in PDGF-A
RT knockout mice.";
RL Development 126:457-467(1999).
RN [6]
RP DISRUPTION PHENOTYPE, AND FUNCTION.
RX PubMed=10903171; DOI=10.1242/dev.127.16.3457;
RA Karlsson L., Lindahl P., Heath J.K., Betsholtz C.;
RT "Abnormal gastrointestinal development in PDGF-A and PDGFR-(alpha)
RT deficient mice implicates a novel mesenchymal structure with putative
RT instructive properties in villus morphogenesis.";
RL Development 127:3457-3466(2000).
RN [7]
RP DISRUPTION PHENOTYPE, AND FUNCTION.
RX PubMed=10831606; DOI=10.1083/jcb.149.5.1019;
RA Gnessi L., Basciani S., Mariani S., Arizzi M., Spera G., Wang C.,
RA Bondjers C., Karlsson L., Betsholtz C.;
RT "Leydig cell loss and spermatogenic arrest in platelet-derived growth
RT factor (PDGF)-A-deficient mice.";
RL J. Cell Biol. 149:1019-1026(2000).
RN [8]
RP DISRUPTION PHENOTYPE, AND FUNCTION.
RX PubMed=11803579; DOI=10.1002/dvdy.1225;
RA Bostrom H., Gritli-Linde A., Betsholtz C.;
RT "PDGF-A/PDGF alpha-receptor signaling is required for lung growth and the
RT formation of alveoli but not for early lung branching morphogenesis.";
RL Dev. Dyn. 223:155-162(2002).
RN [9]
RP TISSUE SPECIFICITY.
RX PubMed=14514732; DOI=10.1097/01.asn.0000089828.73014.c8;
RA Taneda S., Hudkins K.L., Topouzis S., Gilbertson D.G., Ophascharoensuk V.,
RA Truong L., Johnson R.J., Alpers C.E.;
RT "Obstructive uropathy in mice and humans: potential role for PDGF-D in the
RT progression of tubulointerstitial injury.";
RL J. Am. Soc. Nephrol. 14:2544-2555(2003).
RN [10]
RP REVIEW.
RX PubMed=15207812; DOI=10.1016/j.cytogfr.2004.03.003;
RA Tallquist M., Kazlauskas A.;
RT "PDGF signaling in cells and mice.";
RL Cytokine Growth Factor Rev. 15:205-213(2004).
RN [11]
RP REVIEW ON FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=15207813; DOI=10.1016/j.cytogfr.2004.03.005;
RA Betsholtz C.;
RT "Insight into the physiological functions of PDGF through genetic studies
RT in mice.";
RL Cytokine Growth Factor Rev. 15:215-228(2004).
RN [12]
RP FUNCTION.
RX PubMed=19030102; DOI=10.1371/journal.pone.0003794;
RA Wu E., Palmer N., Tian Z., Moseman A.P., Galdzicki M., Wang X., Berger B.,
RA Zhang H., Kohane I.S.;
RT "Comprehensive dissection of PDGF-PDGFR signaling pathways in PDGFR
RT genetically defined cells.";
RL PLoS ONE 3:E3794-E3794(2008).
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.
CC {ECO:0000269|PubMed:10831606, ECO:0000269|PubMed:10903171,
CC ECO:0000269|PubMed:11803579, ECO:0000269|PubMed:19030102,
CC ECO:0000269|PubMed:8681381, ECO:0000269|PubMed:9374392,
CC ECO:0000269|PubMed:9876175}.
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.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=Long;
CC IsoId=P20033-1; Sequence=Displayed;
CC Name=Short;
CC IsoId=P20033-2; Sequence=VSP_004604, VSP_004605;
CC -!- TISSUE SPECIFICITY: Expression primarily localized in papillary regions
CC with presumable expression in tubular cells comprising the loop of
CC Henle. In the renal cortex, a widespread expression seen in the
CC vascular smooth muscle cells and is barely detectable in interstitial
CC cells. {ECO:0000269|PubMed:14514732}.
CC -!- DOMAIN: The long form contains a basic insert which acts as a cell
CC retention signal.
CC -!- DISRUPTION PHENOTYPE: Lethal, due to defects in cell proliferation and
CC migration, leading to defects in the development of the embryonic lung,
CC gastrointestinal tract, oligodendrocytes and Leydig cells.
CC {ECO:0000269|PubMed:10831606, ECO:0000269|PubMed:10903171,
CC ECO:0000269|PubMed:11803579, ECO:0000269|PubMed:15207813,
CC ECO:0000269|PubMed:8681381, ECO:0000269|PubMed:9374392,
CC ECO:0000269|PubMed:9876175}.
CC -!- SIMILARITY: Belongs to the PDGF/VEGF growth factor family.
CC {ECO:0000305}.
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DR EMBL; S66873; AAB28740.2; -; Genomic_DNA.
DR EMBL; S66868; AAB28740.2; JOINED; Genomic_DNA.
DR EMBL; S66869; AAB28740.2; JOINED; Genomic_DNA.
DR EMBL; S66870; AAB28740.2; JOINED; Genomic_DNA.
DR EMBL; S66871; AAB28740.2; JOINED; Genomic_DNA.
DR EMBL; S66872; AAB28740.2; JOINED; Genomic_DNA.
DR EMBL; S66874; AAB28741.2; -; Genomic_DNA.
DR EMBL; S66868; AAB28741.2; JOINED; Genomic_DNA.
DR EMBL; S66869; AAB28741.2; JOINED; Genomic_DNA.
DR EMBL; S66870; AAB28741.2; JOINED; Genomic_DNA.
DR EMBL; S66871; AAB28741.2; JOINED; Genomic_DNA.
DR EMBL; S66872; AAB28741.2; JOINED; Genomic_DNA.
DR EMBL; M29464; AAA39903.1; -; mRNA.
DR CCDS; CCDS19802.1; -. [P20033-2]
DR CCDS; CCDS90003.1; -. [P20033-1]
DR PIR; A37359; A37359.
DR RefSeq; NP_032834.1; NM_008808.3.
DR AlphaFoldDB; P20033; -.
DR SMR; P20033; -.
DR ComplexPortal; CPX-2893; Platelet-derived growth factor AA complex.
DR ComplexPortal; CPX-2899; PDGF receptor alpha - PDGF-AA complex.
DR ComplexPortal; CPX-2900; Platelet-derived growth factor AB complex.
DR ComplexPortal; CPX-2901; PDGF receptor alpha - PDGF-AB complex.
DR ComplexPortal; CPX-2903; PDGF receptor alpha-beta - PDGF-AB complex.
DR ComplexPortal; CPX-2904; PDGF receptor beta - PDGF-AB complex.
DR STRING; 10090.ENSMUSP00000075463; -.
DR GlyGen; P20033; 1 site.
DR PhosphoSitePlus; P20033; -.
DR MaxQB; P20033; -.
DR PaxDb; P20033; -.
DR PeptideAtlas; P20033; -.
DR PRIDE; P20033; -.
DR ProteomicsDB; 294043; -. [P20033-1]
DR ProteomicsDB; 294044; -. [P20033-2]
DR DNASU; 18590; -.
DR GeneID; 18590; -.
DR KEGG; mmu:18590; -.
DR CTD; 5154; -.
DR MGI; MGI:97527; Pdgfa.
DR eggNOG; ENOG502QVAU; Eukaryota.
DR InParanoid; P20033; -.
DR PhylomeDB; P20033; -.
DR Reactome; R-MMU-114608; Platelet degranulation.
DR Reactome; R-MMU-1257604; PIP3 activates AKT signaling.
DR Reactome; R-MMU-186763; Downstream signal transduction.
DR Reactome; R-MMU-186797; Signaling by PDGF.
DR Reactome; R-MMU-3000171; Non-integrin membrane-ECM interactions.
DR Reactome; R-MMU-5673001; RAF/MAP kinase cascade.
DR Reactome; R-MMU-6811558; PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling.
DR BioGRID-ORCS; 18590; 3 hits in 74 CRISPR screens.
DR ChiTaRS; Pdgfa; mouse.
DR PRO; PR:P20033; -.
DR Proteomes; UP000000589; Unplaced.
DR RNAct; P20033; protein.
DR GO; GO:0009986; C:cell surface; ISS:UniProtKB.
DR GO; GO:0005615; C:extracellular space; IDA:BHF-UCL.
DR GO; GO:0016020; C:membrane; IEA:InterPro.
DR GO; GO:0005902; C:microvillus; IDA:MGI.
DR GO; GO:1990265; C:platelet-derived growth factor complex; ISO:MGI.
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:0042802; F:identical protein binding; ISO:MGI.
DR GO; GO:0048407; F:platelet-derived growth factor binding; ISO:MGI.
DR GO; GO:0005161; F:platelet-derived growth factor receptor binding; ISS:UniProtKB.
DR GO; GO:0046982; F:protein heterodimerization activity; ISO:MGI.
DR GO; GO:0042803; F:protein homodimerization activity; ISS:UniProtKB.
DR GO; GO:0030036; P:actin cytoskeleton organization; IDA:MGI.
DR GO; GO:0001525; P:angiogenesis; IDA:MGI.
DR GO; GO:0009887; P:animal organ morphogenesis; IMP:MGI.
DR GO; GO:0060348; P:bone development; IGI:MGI.
DR GO; GO:0008283; P:cell population proliferation; IMP:MGI.
DR GO; GO:0030031; P:cell projection assembly; IDA:MGI.
DR GO; GO:0048565; P:digestive tract development; IMP:UniProtKB.
DR GO; GO:1990401; P:embryonic lung development; IMP:BHF-UCL.
DR GO; GO:0001942; P:hair follicle development; IMP:MGI.
DR GO; GO:0048286; P:lung alveolus development; IMP:UniProtKB.
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:0035790; P:platelet-derived growth factor receptor-alpha signaling pathway; IC:ComplexPortal.
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:MGI.
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; IMP:MGI.
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; IMP:MGI.
DR GO; GO:0050730; P:regulation of peptidyl-tyrosine phosphorylation; IDA:MGI.
DR GO; GO:0014910; P:regulation of smooth muscle cell migration; ISS:UniProtKB.
DR GO; GO:0009611; P:response to wounding; ISS:UniProtKB.
DR GO; GO:0043588; P:skin development; IMP:MGI.
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 PROPEP 21..86
FT /note="Removed in mature form"
FT /id="PRO_0000023358"
FT CHAIN 87..211
FT /note="Platelet-derived growth factor subunit A"
FT /id="PRO_0000023359"
FT REGION 158..162
FT /note="Receptor binding site"
FT /evidence="ECO:0000255"
FT REGION 186..211
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
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:1340209,
FT ECO:0000303|PubMed:2155144"
FT /id="VSP_004604"
FT VAR_SEQ 197..211
FT /note="Missing (in isoform Short)"
FT /evidence="ECO:0000303|PubMed:1340209,
FT ECO:0000303|PubMed:2155144"
FT /id="VSP_004605"
FT CONFLICT 92
FT /note="V -> I (in Ref. 2; AAA39903)"
FT /evidence="ECO:0000305"
FT CONFLICT 174
FT /note="H -> D (in Ref. 1; AAB28740/AAB28741)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 211 AA; 24102 MW; AC4345A10ECF4B39 CRC64;
MRTWACLLLL GCGYLAHALA EEAEIPRELI ERLARSQIHS IRDLQRLLEI DSVGAEDALE
TSLRAHGSHA INHVPEKRPV PIRRKRSIEE AVPAVCKTRT VIYEIPRSQV DPTSANFLIW
PPCVEVKRCT GCCNTSSVKC QPSRVHHRSV KVAKVEYVRK KPKLKEVQVR LEEHLECACA
TSNLNPDHRE EETGRRRESG KNRKRKRLKP T
