Structure of the human neutrophil elastase gene

H. Takahashi, T. Nukiwa, K. Yoshimura, C. D. Quick, D. J. States, M. D. Holmes, J. Whang-Peng, T. Knutsen, R. G. Crystal

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Abstract

The gene for human neutrophil elastase (NE), a powerful serine protease carried by blood neutrophils and capable of destroying most connective tissue proteins, was cloned from a genomic DNA library of a normal individual. The NE gene consists of 5 exons and 4 introns included in a single copy 4-kilobase segment of chromosome 11 at q14. The coding exons of the NE gene predict a primary translation product of 267 residues including a 29-residue N-terminal precursor peptide and a 20-residue C-terminal precursor peptide. Analysis of the N-terminal peptide sequence suggests it contains a 27-residue 'pre' signal peptide followed by a 'pro(N)' dipeptide, similar to that of other blood cell lysosomal proteases. The sequences for the mature 218-residue NE protein are included in exons II-V. The 5'-flanking region of the gene includes typical TATA, CAAT, and GC sequences within 61 base pairs (bp) of the cap site. The sequence 1.5 kilobases 5' to exon I contains several interesting repetitive sequences including six tandem repeats of unique 52- or 53-bp sequences. The 5'-flanking region also contains a 19-bp segment with 90% homology to a segment of the 5'-flanking region of the human myeloperoxidase (MPO) gene, a gene also expressed in bone marrow precursor cells and a protein stored in the same neutrophil granules as NE. In addition, like the MPO gene, the NE 5'-flanking region has several regions with ≥ 75% homology to sequences 5' to c-myc, but there is no overlap between the NE-c-myc and MPO-c-myc homologous sequences.

Original languageEnglish
Pages (from-to)14739-14747
Number of pages9
JournalJournal of Biological Chemistry
Volume263
Issue number29
Publication statusPublished - 1 Jan 1988

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ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Takahashi, H., Nukiwa, T., Yoshimura, K., Quick, C. D., States, D. J., Holmes, M. D., Whang-Peng, J., Knutsen, T., & Crystal, R. G. (1988). Structure of the human neutrophil elastase gene. Journal of Biological Chemistry, 263(29), 14739-14747.