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The human tissue plasminogen activator gene.

S J Degen, B Rajput, E Reich

    The Journal of Biological Chemistry
    |May 25, 1986
    PubMed
    Summary
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    The complete nucleotide sequence of the human tissue plasminogen activator (t-PA) gene was determined. This detailed analysis reveals the gene

    Area of Science:

    • Molecular Biology
    • Genetics
    • Biochemistry

    Background:

    • The human tissue plasminogen activator (t-PA) is a crucial enzyme in fibrinolysis.
    • Understanding the genetic structure of t-PA is essential for comprehending its regulation and function.

    Purpose of the Study:

    • To establish the complete nucleotide sequence of the human t-PA gene.
    • To analyze the structural organization, including exons, introns, and flanking regions.
    • To compare the gene and protein structures with urokinase plasminogen activator (u-PA).

    Main Methods:

    • DNA sequencing of the entire human t-PA gene (36,594 bp).
    • Identification of transcription initiation site using S1 nuclease, exonuclease VII, and primer extension.
    • Bioinformatic analysis and comparison with existing sequence databases.

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    Main Results:

    • The full nucleotide sequence of the human t-PA gene was determined, encompassing coding and flanking regions.
    • The gene comprises 14 coding regions (exons) and 13 intervening sequences (introns), with defined size ranges.
    • Repetitive DNA elements, including Alu and KpnI repeats, were identified within the gene and its 5' flanking region.
    • The transcription initiation site was precisely mapped, with canonical TATA and CAAT boxes located upstream.
    • Comparative analysis revealed close evolutionary relationships between human t-PA and u-PA based on gene and protein structures.

    Conclusions:

    • The detailed sequence and structural analysis of the human t-PA gene provide a comprehensive resource.
    • The findings facilitate a deeper understanding of t-PA gene regulation and evolution.
    • The close evolutionary relationship suggests shared ancestral origins with other plasminogen activators.