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Isolation and structural organization of the human preproenkephalin gene

Nature volume 297, pages 431–434 (1982)Cite this article

Abstract

Recently, we have elucidated the primary structure of bovine adrenal preproenkephalin by determining the nucleotide sequence of cloned DNA complementary to its mRNA1. The structure of most of this precursor molecule has also been deduced by Gubler et al.2 using cDNA sequencing in conjunction with protein sequencing. Bovine preproenkephalin contains four copies of methionine-enkephalin3 (Met-enkephalin) and one copy each of leucine-enkephalin3 (Leu-enkephalin), Met-enkephalin-Arg6-Phe7 (ref. 4) and Met-enkephalin-Arg6-Gly7-Leu8 (refs 1, 2, 5). The region containing the repeated enkephalin and extended enkephalin sequences, which are each bounded by paired basic amino acid residues, is connected with a cysteine-containing amino-terminal sequence preceded by a signal peptide6. We have now studied the relationship between the repetitive structure of preproenkephalin and the structural organization of its gene by cloning a human genomic DNA segment containing the entire gene. We find that the general organization of the preproenkephalin gene is strikingly similar to that of the gene encoding the common precursor of corticotropin (ACTH) and β-lipotropin (β-LPH)7–9 (alternatively designated preproopiomelanocortin), another multi-hormone precursor. Furthermore, the complete mRNA and amino acid sequences of human preproenkephalin have been deduced from the corresponding gene sequence.

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References

  1. Noda, M. et al. Nature 295, 202–206 (1982).

    Article  ADS  CAS  Google Scholar 

  2. Gubler, U., Seeburg, P., Hoffman, B. J., Gage, L. P. & Udenfriend, S. Nature 295, 206–208 (1982).

    Article  ADS  CAS  Google Scholar 

  3. Hughes, J. et al. Nature 258, 577–579 (1975).

    Article  ADS  CAS  Google Scholar 

  4. Stern, A. S. et al. Proc. natn. Acad. Sci. U.S.A. 76, 6680–6683 (1979).

    Article  ADS  CAS  Google Scholar 

  5. Kilpatrick, D. L., Jones, B. N., Kojima, K. & Udenfriend, S. Biochem. biophys. Res. Commun. 103, 698–705 (1981).

    Article  CAS  Google Scholar 

  6. Blobel, G. & Dobberstein, B. J. Cell Biol. 67, 852–862 (1975).

    Article  CAS  Google Scholar 

  7. Nakanishi, S. et al. Nature 287, 752–755 (1980).

    Article  ADS  CAS  Google Scholar 

  8. Nakanishi, S. et al. Eur J. Biochem. 115, 429–438 (1981).

    Article  CAS  Google Scholar 

  9. Takahashi, H., Teranishi, Y., Nakanishi, S. & Numa, S. FEES Lett. 135, 97–102 (1981).

    Article  CAS  Google Scholar 

  10. Lawn, R. M., Fritsch, E. F., Parker, R. C., Blake, G. & Maniatis, T. Cell 15, 1157–1174 (1978).

    Article  CAS  Google Scholar 

  11. Benton, W. D. & Davis, R. W. Science 196, 180–182 (1977).

    Article  ADS  CAS  Google Scholar 

  12. Southern, E. M. J. molec. Biol. 98, 503–517 (1975).

    Article  CAS  Google Scholar 

  13. Lacy, E., Hardison, R. C., Quon, D. & Maniatis, T. Cell 18, 1273–1283 (1979).

    Article  CAS  Google Scholar 

  14. Maxam, A. M. & Gilbert, W. Meth. Enzym. 65, 499–560 (1980).

    Article  CAS  Google Scholar 

  15. Breathnach, R., Benoist, C., O'Hare, K., Gannon, F. & Chambon, P. Proc. natn. Acad. Sci. U.S.A. 75, 4853–4857 (1978).

    Article  ADS  CAS  Google Scholar 

  16. Lerner, M. R., Boyle, J. A., Mount, S. M., Wolin, S. L. & Steitz, J. A. Nature 283, 220–224 (1980).

    Article  ADS  CAS  Google Scholar 

  17. Rogers, J. & Wall, R. Proc. natn. Acad. Sci. U.S.A. 77, 1877–1879 (1980).

    Article  ADS  CAS  Google Scholar 

  18. Berk, A. J. & Sharp, P. A. Cell 12, 721–732 (1977).

    Article  CAS  Google Scholar 

  19. Sollner-Webb, B. & Reeder, R. H. Cell 18, 485–499 (1979).

    Article  CAS  Google Scholar 

  20. Weaver, R. F. & Weissmann, C. Nucleic Acids Res. 7, 1175–1193 (1979).

    Article  CAS  Google Scholar 

  21. Breathnach, R. & Chambon, P. A. Rev. Biochem. 50, 349–383 (1981).

    Article  CAS  Google Scholar 

  22. Goldberg, M. thesis, Stanford Univ. (1979).

  23. Benoist, C., O'Hare, K., Breathnach, R. & Chambon, P. Nucleic Acids Res. 8, 127–142 (1980).

    Article  CAS  Google Scholar 

  24. Sakano, H. et al. Nature 277, 627–633 (1979).

    Article  ADS  CAS  Google Scholar 

  25. Nakanishi, S. et al. Nature 278, 423–427 (1979).

    Article  ADS  CAS  Google Scholar 

  26. Numa, S. & Nakanishi, S. Trends biochem. Sci. 6, 274–277 (1981).

    Article  CAS  Google Scholar 

  27. Perler, F. et al. Cell 20, 555–566 (1980).

    Article  CAS  Google Scholar 

  28. Bell, G. I. et al. Nature 284, 26–32 (1980).

    Article  ADS  CAS  Google Scholar 

  29. Crick, F. Science 204, 264–271 (1979).

    Article  ADS  CAS  Google Scholar 

  30. Comb, M., Seeburg, P. H., Adelman, J., Eiden, L. & Herbert, E. Nature 295, 663–666 (1982).

    Article  ADS  CAS  Google Scholar 

  31. Weinstock, R., Sweet, R., Weiss, M., Cedar, H. & Axel, R. Proc. natn. Acad. Sci. U.S.A. 75, 1299–1303 (1978).

    Article  ADS  CAS  Google Scholar 

  32. Taii, S., Nakanishi, S. & Numa, S. Eur. J. Biochem. 93, 205–212 (1979).

    Article  CAS  Google Scholar 

  33. Rubin, C. M. & Schmid, C. W. Nucleic Acids Res. 8, 4613–4619 (1980).

    Article  CAS  Google Scholar 

  34. Houghton, M. et al. Nucleic Acids Res. 8, 2885–2894 (1980).

    Article  CAS  Google Scholar 

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Authors and Affiliations

  1. Department of Medical Chemistry, Kyoto University Faculty of Medicine, Kyoto, 606, Japan

    Masaharu Noda, Yutaka Teranishi, Hideo Takahashi, Mitsuyoshi Toyosato, Mitsue Notake & Shosaku Numa

  2. Institute for Immunology, Kyoto University Faculty of Medicine, Kyoto, 606, Japan

    Shigetada Nakanishi

Authors
  1. Masaharu Noda
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  2. Yutaka Teranishi
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  3. Hideo Takahashi
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  4. Mitsuyoshi Toyosato
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  5. Mitsue Notake
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  6. Shigetada Nakanishi
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  7. Shosaku Numa
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Noda, M., Teranishi, Y., Takahashi, H. et al. Isolation and structural organization of the human preproenkephalin gene. Nature 297, 431–434 (1982). https://doi.org/10.1038/297431a0

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