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Protein

Platelet-derived growth factor subunit A

Gene

Pdgfa

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at transcript leveli

Functioni

Growth factor that plays an essential role in the regulation of embryonic development, cell proliferation, cell migration, survival and chemotaxis. Potent mitogen for cells of mesenchymal origin. Required for normal lung alveolar septum formation during embryogenesis, normal development of the gastrointestinal tract, normal development of Leydig cells and spermatogenesis. Required for normal oligodendrocyte development and normal myelination in the spinal cord and cerebellum. Plays an important role in wound healing. Signaling is modulated by the formation of heterodimers with PDGFB.7 Publications

GO - Molecular functioni

GO - Biological processi

  • actin cytoskeleton organization Source: MGI
  • angiogenesis Source: MGI
  • blood coagulation Source: GO_Central
  • bone development Source: MGI
  • cell projection assembly Source: MGI
  • digestive tract development Source: UniProtKB
  • embryonic lung development Source: BHF-UCL
  • hair follicle development Source: MGI
  • lung alveolus development Source: UniProtKB
  • negative chemotaxis Source: UniProtKB
  • negative regulation of phosphatidylinositol biosynthetic process Source: UniProtKB
  • negative regulation of platelet activation Source: UniProtKB
  • organ morphogenesis Source: MGI
  • platelet-derived growth factor receptor signaling pathway Source: UniProtKB
  • positive regulation of cell division Source: UniProtKB-KW
  • positive regulation of cell migration Source: UniProtKB
  • positive regulation of cell proliferation Source: MGI
  • positive regulation of DNA replication Source: UniProtKB
  • positive regulation of ERK1 and ERK2 cascade Source: UniProtKB
  • positive regulation of fibroblast proliferation Source: UniProtKB
  • positive regulation of MAPK cascade Source: UniProtKB
  • positive regulation of MAP kinase activity Source: UniProtKB
  • positive regulation of mesenchymal cell proliferation Source: MGI
  • positive regulation of metanephric mesenchymal cell migration by platelet-derived growth factor receptor-beta signaling pathway Source: UniProtKB
  • positive regulation of phosphatidylinositol 3-kinase signaling Source: UniProtKB
  • positive regulation of protein autophosphorylation Source: UniProtKB
  • positive regulation of protein kinase B signaling Source: UniProtKB
  • regulation of branching involved in salivary gland morphogenesis by epithelial-mesenchymal signaling Source: MGI
  • regulation of peptidyl-tyrosine phosphorylation Source: MGI
  • regulation of smooth muscle cell migration Source: UniProtKB
  • response to wounding Source: UniProtKB
  • skin development Source: MGI
Complete GO annotation...

Keywords - Molecular functioni

Developmental protein, Growth factor, Mitogen

Names & Taxonomyi

Protein namesi
Recommended name:
Platelet-derived growth factor subunit A
Short name:
PDGF subunit A
Alternative name(s):
PDGF-1
Platelet-derived growth factor A chain
Platelet-derived growth factor alpha polypeptide
Gene namesi
Name:Pdgfa
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
ProteomesiUP000000589 Componenti: Unplaced

Organism-specific databases

MGIiMGI:97527. Pdgfa.

Subcellular locationi

  • Secreted

  • Note: Released by platelets upon wounding.

GO - Cellular componenti

  • cell surface Source: UniProtKB
  • extracellular space Source: BHF-UCL
  • membrane Source: InterPro
  • microvillus Source: MGI
Complete GO annotation...

Keywords - Cellular componenti

Secreted

Pathology & Biotechi

Disruption phenotypei

Lethal, due to defects in cell proliferation and migration, leading to defects in the development of the embryonic lung, gastrointestinal tract, oligodendrocytes and Leydig cells.7 Publications

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 2020Add
BLAST
Propeptidei21 – 8666Removed in mature formPRO_0000023358Add
BLAST
Chaini87 – 211125Platelet-derived growth factor subunit APRO_0000023359Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Disulfide bondi96 ↔ 140By similarity
Disulfide bondi123 – 123InterchainBy similarity
Disulfide bondi129 ↔ 177By similarity
Disulfide bondi132 – 132InterchainBy similarity
Disulfide bondi133 ↔ 179By similarity
Glycosylationi134 – 1341N-linked (GlcNAc...)Sequence Analysis

Keywords - PTMi

Cleavage on pair of basic residues, Disulfide bond, Glycoprotein

Proteomic databases

MaxQBiP20033.
PaxDbiP20033.
PRIDEiP20033.

PTM databases

PhosphoSiteiP20033.

Expressioni

Tissue specificityi

Expression primarily localized in papillary regions with presumable expression in tubular cells comprising the loop of Henle. In the renal cortex, a widespread expression seen in the vascular smooth muscle cells and is barely detectable in interstitial cells.1 Publication

Gene expression databases

CleanExiMM_PDGFA.
GenevestigatoriP20033.

Interactioni

Subunit structurei

Homodimer; antiparallel disulfide-linked dimer. Heterodimer with PDGFB; antiparallel disulfide-linked dimer. The PDGFA homodimer interacts with PDGFRA homodimers, and with heterodimers formed by PDGFRA and PDGFRB. The heterodimer composed of PDGFA and PDGFB interacts with PDGFRA homodimers, and with heterodimers formed by PDGFRA and PDGFRB. Interacts with CSPG4 (By similarity).By similarity

Structurei

3D structure databases

ProteinModelPortaliP20033.
SMRiP20033. Positions 23-182.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni158 – 1625Receptor binding siteSequence Analysis

Domaini

The long form contains a basic insert which acts as a cell retention signal.

Sequence similaritiesi

Belongs to the PDGF/VEGF growth factor family.Curated

Keywords - Domaini

Signal

Phylogenomic databases

eggNOGiNOG75094.
HOGENOMiHOG000286027.
HOVERGENiHBG053546.
InParanoidiP20033.
KOiK04359.
PhylomeDBiP20033.

Family and domain databases

Gene3Di2.10.90.10. 1 hit.
InterProiIPR029034. Cystine-knot_cytokine.
IPR023581. PD_growth_factor_CS.
IPR000072. PDGF/VEGF_dom.
IPR006782. PDGF_N.
[Graphical view]
PfamiPF00341. PDGF. 1 hit.
PF04692. PDGF_N. 1 hit.
[Graphical view]
SMARTiSM00141. PDGF. 1 hit.
[Graphical view]
SUPFAMiSSF57501. SSF57501. 1 hit.
PROSITEiPS00249. PDGF_1. 1 hit.
PS50278. PDGF_2. 1 hit.
[Graphical view]

Sequences (2)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform Long (identifier: P20033-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MRTWACLLLL GCGYLAHALA EEAEIPRELI ERLARSQIHS IRDLQRLLEI
60 70 80 90 100
DSVGAEDALE TSLRAHGSHA INHVPEKRPV PIRRKRSIEE AVPAVCKTRT
110 120 130 140 150
VIYEIPRSQV DPTSANFLIW PPCVEVKRCT GCCNTSSVKC QPSRVHHRSV
160 170 180 190 200
KVAKVEYVRK KPKLKEVQVR LEEHLECACA TSNLNPDHRE EETGRRRESG
210
KNRKRKRLKP T
Length:211
Mass (Da):24,102
Last modified:October 1, 1996 - v2
Checksum:iAC4345A10ECF4B39
GO
Isoform Short (identifier: P20033-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     194-196: GRR → DVR
     197-211: Missing.

Show »
Length:196
Mass (Da):22,267
Checksum:i3F219DA70E4007D4
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti92 – 921V → I in AAA39903 (PubMed:2155144).Curated
Sequence conflicti174 – 1741H → D in AAB28740 (PubMed:1340209).Curated
Sequence conflicti174 – 1741H → D in AAB28741 (PubMed:1340209).Curated

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei194 – 1963GRR → DVR in isoform Short. 2 PublicationsVSP_004604
Alternative sequencei197 – 21115Missing in isoform Short. 2 PublicationsVSP_004605Add
BLAST

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
S66873
, S66868, S66869, S66870, S66871, S66872 Genomic DNA. Translation: AAB28740.2.
S66874
, S66868, S66869, S66870, S66871, S66872 Genomic DNA. Translation: AAB28741.2.
M29464 mRNA. Translation: AAA39903.1.
CCDSiCCDS19802.1. [P20033-2]
PIRiA37359.
RefSeqiNP_032834.1. NM_008808.3.
UniGeneiMm.2675.

Genome annotation databases

GeneIDi18590.
KEGGimmu:18590.

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
S66873
, S66868, S66869, S66870, S66871, S66872 Genomic DNA. Translation: AAB28740.2.
S66874
, S66868, S66869, S66870, S66871, S66872 Genomic DNA. Translation: AAB28741.2.
M29464 mRNA. Translation: AAA39903.1.
CCDSiCCDS19802.1. [P20033-2]
PIRiA37359.
RefSeqiNP_032834.1. NM_008808.3.
UniGeneiMm.2675.

3D structure databases

ProteinModelPortaliP20033.
SMRiP20033. Positions 23-182.
ModBaseiSearch...
MobiDBiSearch...

PTM databases

PhosphoSiteiP20033.

Proteomic databases

MaxQBiP20033.
PaxDbiP20033.
PRIDEiP20033.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

GeneIDi18590.
KEGGimmu:18590.

Organism-specific databases

CTDi5154.
MGIiMGI:97527. Pdgfa.

Phylogenomic databases

eggNOGiNOG75094.
HOGENOMiHOG000286027.
HOVERGENiHBG053546.
InParanoidiP20033.
KOiK04359.
PhylomeDBiP20033.

Miscellaneous databases

NextBioi294472.
PROiP20033.
SOURCEiSearch...

Gene expression databases

CleanExiMM_PDGFA.
GenevestigatoriP20033.

Family and domain databases

Gene3Di2.10.90.10. 1 hit.
InterProiIPR029034. Cystine-knot_cytokine.
IPR023581. PD_growth_factor_CS.
IPR000072. PDGF/VEGF_dom.
IPR006782. PDGF_N.
[Graphical view]
PfamiPF00341. PDGF. 1 hit.
PF04692. PDGF_N. 1 hit.
[Graphical view]
SMARTiSM00141. PDGF. 1 hit.
[Graphical view]
SUPFAMiSSF57501. SSF57501. 1 hit.
PROSITEiPS00249. PDGF_1. 1 hit.
PS50278. PDGF_2. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

  1. "Characterization of the mouse PDGF A-chain gene. Evolutionary conservation of gene structure, nucleotide sequence and alternative splicing."
    Rorsman F., Betsholtz C.
    Growth Factors 6:303-313(1992) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORMS LONG AND SHORT).
    Strain: BALB/c.
  2. "Selective expression of PDGF A and its receptor during early mouse embryogenesis."
    Mercola M., Wang C., Kelly J., Brownlee C., Jackson-Grusby L., Stiles C., Bowen-Pope D.F.
    Dev. Biol. 138:114-122(1990) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM SHORT).
    Strain: F9.
  3. "PDGF-A signaling is a critical event in lung alveolar myofibroblast development and alveogenesis."
    Bostrom H., Willetts K., Pekny M., Leveen P., Lindahl P., Hedstrand H., Pekna M., Hellstrom M., Gebre-Medhin S., Schalling M., Nilsson M., Kurland S., Tornell J., Heath J.K., Betsholtz C.
    Cell 85:863-873(1996) [PubMed] [Europe PMC] [Abstract]
    Cited for: DISRUPTION PHENOTYPE, FUNCTION.
  4. "Alveogenesis failure in PDGF-A-deficient mice is coupled to lack of distal spreading of alveolar smooth muscle cell progenitors during lung development."
    Lindahl P., Karlsson L., Hellstrom M., Gebre-Medhin S., Willetts K., Heath J.K., Betsholtz C.
    Development 124:3943-3953(1997) [PubMed] [Europe PMC] [Abstract]
    Cited for: DISRUPTION PHENOTYPE, FUNCTION.
  5. "Defective oligodendrocyte development and severe hypomyelination in PDGF-A knockout mice."
    Fruttiger M., Karlsson L., Hall A.C., Abramsson A., Calver A.R., Bostrom H., Willetts K., Bertold C.H., Heath J.K., Betsholtz C., Richardson W.D.
    Development 126:457-467(1999) [PubMed] [Europe PMC] [Abstract]
    Cited for: DISRUPTION PHENOTYPE, FUNCTION.
  6. "Abnormal gastrointestinal development in PDGF-A and PDGFR-(alpha) deficient mice implicates a novel mesenchymal structure with putative instructive properties in villus morphogenesis."
    Karlsson L., Lindahl P., Heath J.K., Betsholtz C.
    Development 127:3457-3466(2000) [PubMed] [Europe PMC] [Abstract]
    Cited for: DISRUPTION PHENOTYPE, FUNCTION.
  7. "Leydig cell loss and spermatogenic arrest in platelet-derived growth factor (PDGF)-A-deficient mice."
    Gnessi L., Basciani S., Mariani S., Arizzi M., Spera G., Wang C., Bondjers C., Karlsson L., Betsholtz C.
    J. Cell Biol. 149:1019-1026(2000) [PubMed] [Europe PMC] [Abstract]
    Cited for: DISRUPTION PHENOTYPE, FUNCTION.
  8. "PDGF-A/PDGF alpha-receptor signaling is required for lung growth and the formation of alveoli but not for early lung branching morphogenesis."
    Bostrom H., Gritli-Linde A., Betsholtz C.
    Dev. Dyn. 223:155-162(2002) [PubMed] [Europe PMC] [Abstract]
    Cited for: DISRUPTION PHENOTYPE, FUNCTION.
  9. "Obstructive uropathy in mice and humans: potential role for PDGF-D in the progression of tubulointerstitial injury."
    Taneda S., Hudkins K.L., Topouzis S., Gilbertson D.G., Ophascharoensuk V., Truong L., Johnson R.J., Alpers C.E.
    J. Am. Soc. Nephrol. 14:2544-2555(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: TISSUE SPECIFICITY.
  10. Cited for: REVIEW.
  11. "Insight into the physiological functions of PDGF through genetic studies in mice."
    Betsholtz C.
    Cytokine Growth Factor Rev. 15:215-228(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: REVIEW ON FUNCTION, DISRUPTION PHENOTYPE.
  12. "Comprehensive dissection of PDGF-PDGFR signaling pathways in PDGFR genetically defined cells."
    Wu E., Palmer N., Tian Z., Moseman A.P., Galdzicki M., Wang X., Berger B., Zhang H., Kohane I.S.
    PLoS ONE 3:E3794-E3794(2008) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION.

Entry informationi

Entry nameiPDGFA_MOUSE
AccessioniPrimary (citable) accession number: P20033
Entry historyi
Integrated into UniProtKB/Swiss-Prot: February 1, 1991
Last sequence update: October 1, 1996
Last modified: May 27, 2015
This is version 143 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into Uniref entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.