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Structure and evolutionary origin of the human granzyme H gene

Haddad, Patrick ; Jenne, Dieter ; Tschopp, Jürg ; Clément, Marie-Véronique ; Mathieu-Mahul, Danièle ; Sasportes, Marilyne

In: International Immunology, 1991, vol. 3, no. 1, p. 57-66

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    Titre
    • Structure and evolutionary origin of the human granzyme H gene
    Auteur
    • Haddad, Patrick. Unité 93 INSERM, 1 avenue C. Vellefaux, CH-1066 Epalinges, Switzerland, 27 rue J. Dodu, 75010 Paris, France
    • Jenne, Dieter. Institute of Biochemistry University of Lausanne CH-1066 Epalinges, Switzerland
    • Tschopp, Jürg. Institute of Biochemistry University of Lausanne CH-1066 Epalinges, Switzerland
    • Clément, Marie-Véronique. Institute of Biochemistry University of Lausanne CH-1066 Epalinges, Switzerland
    • Mathieu-Mahul, Danièle. Unité 301 INSERM 27 rue J. Dodu, 75010 Paris, France
    • Sasportes, Marilyne. Unité 93 INSERM, 1 avenue C. Vellefaux, CH-1066 Epalinges, Switzerland, 27 rue J. Dodu, 75010 Paris, France
    Type de document
    • Postprint
    Langue
    • Anglais
    Publié dans
    • International Immunology, 1991, vol. 3, no. 1, p. 57-66. Oxford University Press
    Autre version électronique
    Identifiant OAI-PMH
    • oai:doc.rero.ch:299888
    Summary
    Among the molecules proposed to be involved In cytotoxic T lymphocyte (CTL), natural killer (NK) and lymphokine activated killer (LAK) cell-mediated lysis are the granzymes, a family of serine proteases stored in the cytoplasmic granules of CTLs, NK and LAK cells. In addition to the granzymes A and B, a third member of this family has been cloned in man and designated granzyme H. We present the complete gene sequence including the 5' promoter region and demonstrate that the granzyme H sequence represents a functional gene expressed In activated T cells. Granzyme H shows the highest degree (>54%) of amlno acid sequence homology with granzyme B and cathepsin G and, like these genes, consists of five exons separated by introns at equivalent positions. The evolutionary history of granzyme H has been analyzed by reconstructing an evolutionary tree for granzyme sequences. We provide evidence that Interlocus recombination between the ancestral genes of granzyme B and granzyme H occurred about 21 million years ago, leading to a replacement of exon 3, Intron 3 and part of exon 4 in human granzyme H by human granzyme B sequences. Our results suggest that the ancestral gene of granzyme H is more closely related to cathepsin G and granzyme B than to the murine granzymes C to G; Thus, granzyme H does not represent a human counterpart of the known murine granzymes A to G. It diverged from cathepsin G before mammalian radiation and should, therefore, exist in other mammalian lineages as well