Skip to main content
PMC home page
Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1991 Jun 15;88(12):5272–5276. doi: 10.1073/pnas.88.12.5272

A single base insertion in the putative transmembrane domain of the tyrosinase gene as a cause for tyrosinase-negative oculocutaneous albinism.

C D Chintamaneni 1, R Halaban 1, Y Kobayashi 1, C J Witkop Jr 1, B S Kwon 1
PMCID: PMC51854  PMID: 1711223

Abstract

We have determined a molecular defect to be the likely basis for inactivity of the tyrosinase (EC 1.14.18.1) from a patient with tyrosinase-negative oculocutaneous albinism. A single base (thymine) was inserted in exon 5 of the tyrosinase gene following codon 471 in the putative transmembrane coding region. This insertion caused a shift in the reading frame of 19 amino acids at the 3' end and introduced a premature termination signal that would be expected to truncate the protein by 21 amino acids at the carboxyl terminus. The albino tyrosinase was not recognized by antibodies directed to the carboxyl terminus of tyrosinase. Furthermore, as shown by gel electrophoresis of the immunoprecipitated protein, the tyrosinase was approximately 3 kDa smaller than normal. Similar immunoprecipitation data were obtained when cloned normal and mutant tyrosinases were expressed in COS-1 cells.

Full text

PDF
5272

Images in this article

5273Image
on p.5273
5273Image
on p.5273
5275Image
on p.5275
5275Image
on p.5275
5275Image
on p.5275
5275Image
on p.5275

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Barton D. E., Kwon B. S., Francke U. Human tyrosinase gene, mapped to chromosome 11 (q14----q21), defines second region of homology with mouse chromosome 7. Genomics. 1988 Jul;3(1):17–24. doi: 10.1016/0888-7543(88)90153-x. [DOI] [PubMed] [Google Scholar]
  2. Bouchard B., Fuller B. B., Vijayasaradhi S., Houghton A. N. Induction of pigmentation in mouse fibroblasts by expression of human tyrosinase cDNA. J Exp Med. 1989 Jun 1;169(6):2029–2042. doi: 10.1084/jem.169.6.2029. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Chen E. Y., Seeburg P. H. Supercoil sequencing: a fast and simple method for sequencing plasmid DNA. DNA. 1985 Apr;4(2):165–170. doi: 10.1089/dna.1985.4.165. [DOI] [PubMed] [Google Scholar]
  4. Giebel L. B., Strunk K. M., King R. A., Hanifin J. M., Spritz R. A. A frequent tyrosinase gene mutation in classic, tyrosinase-negative (type IA) oculocutaneous albinism. Proc Natl Acad Sci U S A. 1990 May;87(9):3255–3258. doi: 10.1073/pnas.87.9.3255. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Gould S. J., Keller G. A., Subramani S. Identification of peroxisomal targeting signals located at the carboxy terminus of four peroxisomal proteins. J Cell Biol. 1988 Sep;107(3):897–905. doi: 10.1083/jcb.107.3.897. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Halaban R., Moellmann G. Murine and human b locus pigmentation genes encode a glycoprotein (gp75) with catalase activity. Proc Natl Acad Sci U S A. 1990 Jun;87(12):4809–4813. doi: 10.1073/pnas.87.12.4809. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Halaban R., Pomerantz S. H., Marshall S., Lambert D. T., Lerner A. B. Regulation of tyrosinase in human melanocytes grown in culture. J Cell Biol. 1983 Aug;97(2):480–488. doi: 10.1083/jcb.97.2.480. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Jiménez M., Tsukamoto K., Hearing V. J. Tyrosinases from two different loci are expressed by normal and by transformed melanocytes. J Biol Chem. 1991 Jan 15;266(2):1147–1156. [PubMed] [Google Scholar]
  9. King R. A., Witkop C. J., Jr Hairbulb tyrosinase activity in oculocutaneous albinism. Nature. 1976 Sep 2;263(5572):69–71. doi: 10.1038/263069a0. [DOI] [PubMed] [Google Scholar]
  10. Kwon B. S., Halaban R., Chintamaneni C. Molecular basis of mouse Himalayan mutation. Biochem Biophys Res Commun. 1989 May 30;161(1):252–260. doi: 10.1016/0006-291x(89)91588-x. [DOI] [PubMed] [Google Scholar]
  11. Kwon B. S., Halaban R., Kim G. S., Usack L., Pomerantz S., Haq A. K. A melanocyte-specific complementary DNA clone whose expression is inducible by melanotropin and isobutylmethyl xanthine. Mol Biol Med. 1987 Dec;4(6):339–355. [PubMed] [Google Scholar]
  12. Kwon B. S., Haq A. K., Pomerantz S. H., Halaban R. Isolation and sequence of a cDNA clone for human tyrosinase that maps at the mouse c-albino locus. Proc Natl Acad Sci U S A. 1987 Nov;84(21):7473–7477. doi: 10.1073/pnas.84.21.7473. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Kwon B. S., Kim G. S., Prystowsky M. B., Lancki D. W., Sabath D. E., Pan J. L., Weissman S. M. Isolation and initial characterization of multiple species of T-lymphocyte subset cDNA clones. Proc Natl Acad Sci U S A. 1987 May;84(9):2896–2900. doi: 10.1073/pnas.84.9.2896. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Kwon B. S., Wakulchik M., Haq A. K., Halaban R., Kestler D. Sequence analysis of mouse tyrosinase cDNA and the effect of melanotropin on its gene expression. Biochem Biophys Res Commun. 1988 Jun 30;153(3):1301–1309. doi: 10.1016/s0006-291x(88)81370-6. [DOI] [PubMed] [Google Scholar]
  15. Körner A., Pawelek J. Mammalian tyrosinase catalyzes three reactions in the biosynthesis of melanin. Science. 1982 Sep 17;217(4565):1163–1165. doi: 10.1126/science.6810464. [DOI] [PubMed] [Google Scholar]
  16. Pomerantz S. H. L-tyrosine-3,5-3H assay for tyrosinase development in skin of newborn hamsters. Science. 1969 May 16;164(3881):838–839. doi: 10.1126/science.164.3881.838. [DOI] [PubMed] [Google Scholar]
  17. Pomerantz S. H. The tyrosine hydroxylase activity of mammalian tyrosinase. J Biol Chem. 1966 Jan 10;241(1):161–168. [PubMed] [Google Scholar]
  18. Ruppert S., Müller G., Kwon B., Schütz G. Multiple transcripts of the mouse tyrosinase gene are generated by alternative splicing. EMBO J. 1988 Sep;7(9):2715–2722. doi: 10.1002/j.1460-2075.1988.tb03125.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. SHIMAO K. Partial purification and kinetic studies of mammalian tyrosinase. Biochim Biophys Acta. 1962 Aug 13;62:205–215. doi: 10.1016/0006-3002(62)90034-3. [DOI] [PubMed] [Google Scholar]
  20. Sanger F., Nicklen S., Coulson A. R. DNA sequencing with chain-terminating inhibitors. Proc Natl Acad Sci U S A. 1977 Dec;74(12):5463–5467. doi: 10.1073/pnas.74.12.5463. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Shibahara S., Tomita Y., Sakakura T., Nager C., Chaudhuri B., Müller R. Cloning and expression of cDNA encoding mouse tyrosinase. Nucleic Acids Res. 1986 Mar 25;14(6):2413–2427. doi: 10.1093/nar/14.6.2413. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Shibahara S., Tomita Y., Tagami H., Müller R. M., Cohen T. Molecular basis for the heterogeneity of human tyrosinase. Tohoku J Exp Med. 1988 Dec;156(4):403–414. doi: 10.1620/tjem.156.403. [DOI] [PubMed] [Google Scholar]
  23. Southern E. M. Detection of specific sequences among DNA fragments separated by gel electrophoresis. J Mol Biol. 1975 Nov 5;98(3):503–517. doi: 10.1016/s0022-2836(75)80083-0. [DOI] [PubMed] [Google Scholar]
  24. Spritz R. A., Strunk K. M., Giebel L. B., King R. A. Detection of mutations in the tyrosinase gene in a patient with type IA oculocutaneous albinism. N Engl J Med. 1990 Jun 14;322(24):1724–1728. doi: 10.1056/NEJM199006143222407. [DOI] [PubMed] [Google Scholar]
  25. Spritz R., Strunk K., Oetting W., King R. RFLP for TaqI at the human tyrosinase locus. Nucleic Acids Res. 1988 Oct 25;16(20):9890–9890. doi: 10.1093/nar/16.20.9890. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Thomas P. S. Hybridization of denatured RNA and small DNA fragments transferred to nitrocellulose. Proc Natl Acad Sci U S A. 1980 Sep;77(9):5201–5205. doi: 10.1073/pnas.77.9.5201. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Tomita Y., Takeda A., Okinaga S., Tagami H., Shibahara S. Human oculocutaneous albinism caused by single base insertion in the tyrosinase gene. Biochem Biophys Res Commun. 1989 Nov 15;164(3):990–996. doi: 10.1016/0006-291x(89)91767-1. [DOI] [PubMed] [Google Scholar]
  28. Wittbjer A., Dahlbäck B., Odh G., Rosengren A. M., Rosengren E., Rorsman H. Isolation of human tyrosinase from cultured melanoma cells. Acta Derm Venereol. 1989;69(2):125–131. [PubMed] [Google Scholar]
  29. Yang Y. C., Ciarletta A. B., Temple P. A., Chung M. P., Kovacic S., Witek-Giannotti J. S., Leary A. C., Kriz R., Donahue R. E., Wong G. G. Human IL-3 (multi-CSF): identification by expression cloning of a novel hematopoietic growth factor related to murine IL-3. Cell. 1986 Oct 10;47(1):3–10. doi: 10.1016/0092-8674(86)90360-0. [DOI] [PubMed] [Google Scholar]
  30. Young R. A., Davis R. W. Efficient isolation of genes by using antibody probes. Proc Natl Acad Sci U S A. 1983 Mar;80(5):1194–1198. doi: 10.1073/pnas.80.5.1194. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Proceedings of the National Academy of Sciences of the United States of America are provided here courtesy of National Academy of Sciences

RESOURCES