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P20033

- PDGFA_MOUSE

UniProt

P20033 - PDGFA_MOUSE

Protein

Platelet-derived growth factor subunit A

Gene

Pdgfa

Organism
Mus musculus (Mouse)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at transcript leveli
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    • History
      Entry version 139 (01 Oct 2014)
      Sequence version 2 (01 Oct 1996)
      Previous versions | rss
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    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

    1. collagen binding Source: UniProtKB
    2. growth factor activity Source: UniProtKB
    3. platelet-derived growth factor receptor binding Source: UniProtKB
    4. protein homodimerization activity Source: UniProtKB

    GO - Biological processi

    1. actin cytoskeleton organization Source: MGI
    2. angiogenesis Source: MGI
    3. blood coagulation Source: RefGenome
    4. cell projection assembly Source: MGI
    5. digestive tract development Source: UniProtKB
    6. hair follicle development Source: MGI
    7. lung alveolus development Source: UniProtKB
    8. negative chemotaxis Source: UniProtKB
    9. negative regulation of phosphatidylinositol biosynthetic process Source: UniProtKB
    10. negative regulation of platelet activation Source: UniProtKB
    11. organ morphogenesis Source: MGI
    12. platelet-derived growth factor receptor signaling pathway Source: UniProtKB
    13. positive regulation of cell division Source: UniProtKB-KW
    14. positive regulation of cell migration Source: UniProtKB
    15. positive regulation of cell proliferation Source: MGI
    16. positive regulation of DNA replication Source: UniProtKB
    17. positive regulation of ERK1 and ERK2 cascade Source: UniProtKB
    18. positive regulation of fibroblast proliferation Source: UniProtKB
    19. positive regulation of MAPK cascade Source: UniProtKB
    20. positive regulation of MAP kinase activity Source: UniProtKB
    21. positive regulation of mesenchymal cell proliferation Source: MGI
    22. positive regulation of metanephric mesenchymal cell migration by platelet-derived growth factor receptor-beta signaling pathway Source: UniProtKB
    23. positive regulation of phosphatidylinositol 3-kinase signaling Source: UniProtKB
    24. positive regulation of protein autophosphorylation Source: UniProtKB
    25. positive regulation of protein kinase B signaling Source: UniProtKB
    26. regulation of branching involved in salivary gland morphogenesis by epithelial-mesenchymal signaling Source: MGI
    27. regulation of peptidyl-tyrosine phosphorylation Source: MGI
    28. regulation of smooth muscle cell migration Source: UniProtKB
    29. response to wounding Source: UniProtKB
    30. skin development Source: MGI

    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: Unplaced

    Organism-specific databases

    MGIiMGI:97527. Pdgfa.

    Subcellular locationi

    Secreted
    Note: Released by platelets upon wounding.

    GO - Cellular componenti

    1. cell surface Source: UniProtKB
    2. extracellular space Source: BHF-UCL
    3. membrane Source: InterPro
    4. microvillus Source: MGI

    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

    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. Align

    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

    MRTWACLLLL GCGYLAHALA EEAEIPRELI ERLARSQIHS IRDLQRLLEI    50
    DSVGAEDALE TSLRAHGSHA INHVPEKRPV PIRRKRSIEE AVPAVCKTRT 100
    VIYEIPRSQV DPTSANFLIW PPCVEVKRCT GCCNTSSVKC QPSRVHHRSV 150
    KVAKVEYVRK KPKLKEVQVR LEEHLECACA TSNLNPDHRE EETGRRRESG 200
    KNRKRKRLKP T 211
    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:
    EMBL
    GenBank
    DDBJ
    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:
    EMBL
    GenBank
    DDBJ
    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 .
    CCDSi CCDS19802.1. [P20033-2 ]
    PIRi A37359.
    RefSeqi NP_032834.1. NM_008808.3.
    UniGenei Mm.2675.

    3D structure databases

    ProteinModelPortali P20033.
    SMRi P20033. Positions 23-182.
    ModBasei Search...
    MobiDBi Search...

    PTM databases

    PhosphoSitei P20033.

    Proteomic databases

    PaxDbi P20033.
    PRIDEi P20033.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    GeneIDi 18590.
    KEGGi mmu:18590.

    Organism-specific databases

    CTDi 5154.
    MGIi MGI:97527. Pdgfa.

    Phylogenomic databases

    eggNOGi NOG75094.
    HOGENOMi HOG000286027.
    HOVERGENi HBG053546.
    InParanoidi P20033.
    KOi K04359.
    PhylomeDBi P20033.

    Miscellaneous databases

    NextBioi 294472.
    PROi P20033.
    SOURCEi Search...

    Gene expression databases

    CleanExi MM_PDGFA.
    Genevestigatori P20033.

    Family and domain databases

    Gene3Di 2.10.90.10. 1 hit.
    InterProi IPR029034. Cystine-knot_cytokine.
    IPR023581. PD_growth_factor_CS.
    IPR000072. PDGF/VEGF_dom.
    IPR006782. PDGF_N.
    [Graphical view ]
    Pfami PF00341. PDGF. 1 hit.
    PF04692. PDGF_N. 1 hit.
    [Graphical view ]
    SMARTi SM00141. PDGF. 1 hit.
    [Graphical view ]
    SUPFAMi SSF57501. SSF57501. 1 hit.
    PROSITEi PS00249. PDGF_1. 1 hit.
    PS50278. PDGF_2. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    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: October 1, 2014
    This is version 139 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