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, Ronald Crystal

Research output: Contribution to journalArticle

93 Citations (Scopus)

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
Externally publishedYes

Fingerprint

Leukocyte Elastase
Genes
5' Flanking Region
Exons
Base Pairing
Peroxidase
Sequence Homology
Peptides
Neutrophils
Blood
Chromosomes, Human, Pair 11
Proteins
Tandem Repeat Sequences
Genomic Library
Dipeptides
Nucleic Acid Repetitive Sequences
Serine Proteases
Chromosomes
Protein Sorting Signals
Gene Library

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., ... Crystal, R. (1988). Structure of the human neutrophil elastase gene. Journal of Biological Chemistry, 263(29), 14739-14747.

Structure of the human neutrophil elastase gene. / Takahashi, H.; Nukiwa, T.; Yoshimura, K.; Quick, C. D.; States, D. J.; Holmes, M. D.; Whang-Peng, J.; Knutsen, T.; Crystal, Ronald.

In: Journal of Biological Chemistry, Vol. 263, No. 29, 01.01.1988, p. 14739-14747.

Research output: Contribution to journalArticle

Takahashi, H, Nukiwa, T, Yoshimura, K, Quick, CD, States, DJ, Holmes, MD, Whang-Peng, J, Knutsen, T & Crystal, R 1988, 'Structure of the human neutrophil elastase gene', Journal of Biological Chemistry, vol. 263, no. 29, pp. 14739-14747.
Takahashi H, Nukiwa T, Yoshimura K, Quick CD, States DJ, Holmes MD et al. Structure of the human neutrophil elastase gene. Journal of Biological Chemistry. 1988 Jan 1;263(29):14739-14747.
Takahashi, H. ; Nukiwa, T. ; Yoshimura, K. ; Quick, C. D. ; States, D. J. ; Holmes, M. D. ; Whang-Peng, J. ; Knutsen, T. ; Crystal, Ronald. / Structure of the human neutrophil elastase gene. In: Journal of Biological Chemistry. 1988 ; Vol. 263, No. 29. pp. 14739-14747.
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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.",
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