Molecules and Cells

Korean Society for Molecular and Cellular Biology (한국분자세포생물학회)
권호 표지

Cloning and Characterization of TMPRSS6, a Novel Type 2 Transmembrane Serine Protease

  • Park, Tae Joo (Department of Life Science, National Research Laboratory of Proteolysis, Gwangju Institute of Science and Technology) ;
  • Lee, Yong Jae (Department of Life Science, National Research Laboratory of Proteolysis, Gwangju Institute of Science and Technology) ;
  • Kim, Hye Jin (Department of Life Science, National Research Laboratory of Proteolysis, Gwangju Institute of Science and Technology) ;
  • Park, Hye Gyeong (Research Institute of Genetic Engineering, Pusan National University) ;
  • Park, Woo Jin (Department of Life Science, National Research Laboratory of Proteolysis, Gwangju Institute of Science and Technology)
  • Received : 2004.10.19
  • Accepted : 2004.12.06
  • Published : 2005.04.30
⟨ Previous Next ⟩

Abstract

We have identified TMPRSS6, a novel type 2 transmembrane serine protease. TMPRSS6 possesses all the signature motifs of the family of transmembrane serine proteases (TMPRSSs), including a transmembrane domain, an LDL receptor class A (LDLRA) domain, a scavenger receptor cysteine-rich (SRCR) domain, and a serine protease domain. The substrate specificity of TMPRSS6 is slightly different from those of other TMPRSS family members. Combined with the finding that TMPRSS6 is expressed strongly in the thyroid and weakly in the trachea, this may indicate that TMPRSS6 has a specialized role.

Keywords

Acknowledgement

Supported by : Ministry of Science and Technology

References

  1. Ben-Yosef, T., Wattenhofer, M., Riazuddin, S., Ahmed, Z. M., Scott, H. S., et al. (2001) Novel mutations of TMPRSS3 in four DFNB8/B10 families segregating congenital autosomal recessive deafness. J. Med. Genet. 38, 396-400 https://doi.org/10.1136/jmg.38.6.396
  2. Gietz, D., St. Jean, A., Woods, R. A., and Schiestl, R. H. (1992) Improved method for igh efficiency transformation of intact yeast cells. Nucleic Acids Res. 20, 1425 https://doi.org/10.1093/nar/20.6.1425
  3. Guipponi, M., Vuagniaux, G., Wattenhofer, M., Shibuya, K., Vazquez, M., et al. (2002) The transmembrane serine protease (TMPRSS3) mutated in deafness DFNB8/10 activates the epithelial sodium channel (ENaC) in vitro. Hum. Mol. Genet. 11, 2829-2836 https://doi.org/10.1093/hmg/11.23.2829
  4. Hooper, J. D., Clements, J. A., Quigley, J. P., and Antalis, T. M. (2001) Type II transmembrane serine proteases. Insights into an emerging class of cell surface proteolytic enzymes. J. Biol. Chem. 276, 857-860 https://doi.org/10.1074/jbc.R000020200
  5. Jacquinet, E., Rao, N. V., Rao, G. V., and Hoidal, J. R. (2000) Cloning, genomic organization, chromosomal assignment and expression of a novel mosaic serine proteinase: epitheliasin. FEBS Lett. 478, 93-100 https://doi.org/10.1016/S0014-5793(00)01826-3
  6. Kang, H., Kim, S. Y., and Park, W. J. (2001) An improved strategy for a genetic assay for site-specific proteolysis. Mol. Cells 11, 263-266
  7. Kim, D. R., Sharmin, S., Inoue, M., and Kido, H. (2001) Cloning and expression of novel mosaic serine proteases with and without a transmembrane domain from human lung. Biochim. Biophys. Acta 1518, 204-209 https://doi.org/10.1016/S0167-4781(01)00184-1
  8. Kim, S. Y., Park, D., Oh, M., Sellamuthu, S., and Park, W. J. (2002) Detection of site-specific proteolysis in secretory pathways. Biochem. Biophys. Res. Commun. 296, 419-424 https://doi.org/10.1016/S0006-291X(02)00868-9
  9. Klein, R. D., Gu, Q., Goddard, A., and Rosenthal, A. (1996) Selection for genes encoding secreted proteins and receptors. Proc. Natl. Acad. Sci. USA 93, 7108-7113
  10. Kozak, M. (1995) Adherence to the first-AUG rule when a second AUG codon follows closely upon the first. Proc. Natl. Acad. Sci. USA 15, 8125-8148
  11. Lee, Y. J., Park, D., Kim, S. Y., and Park, W. J. (2003) Pathogenic mutation but not polymorphisms in congenital and childhood onset autosomal recessive deafness disrupt the proteolytic activity of TMPRSS3. J. Med. Genet. 40, 629- 631 https://doi.org/10.1136/jmg.40.8.629
  12. Lin, B., Ferguson, C., White, J. T., Wang, S., Vessella, R., et al. (1999) Prostate-localized and androgen-regulated expression of the membrane-bound serine protease TMPRSS2. Cancer Res. 59, 4180-4184
  13. Lopez-Otin, C. and Overall, C. M. (2002) Protease degradomics: a new challenge for proteomics. Nat. Rev. Mol. Cell. Biol. 3, 509-519 https://doi.org/10.1038/nrm858
  14. Masmoudi, S., Antonarakis, S. E., Schwede, T., Ghorbel, A. M., Gratri, M., et al. (2001) Novel missense mutations of TMPRSS3 in two consanguineous Tunisian families with non-syndromic autosomal recessive deafness. Hum. Mutat. 18, 101-108 https://doi.org/10.1002/humu.1159
  15. Nielsen, H., Engelbrecht, J., Brunak, S., and von Heijne, G. (1997) A neural network method for identification of prokaryotic and eukaryotic signal peptides and prediction of their cleavage sites. Int. J. Neural. Syst. 8, 581-599 https://doi.org/10.1142/S0129065797000537
  16. Oh, E. S. and Couchman, J. R. (2004) Syndecans-2 and -4; close cousins, but not identical twins. Mol. Cells 17, 181-187
  17. Scott, H. S., Kudoh, J., Wattenhofer, M., Shibuya, K., Berry, A., et al. (2001) Insertion of beta-satellite repeats identifies a transmembrane protease causing both congenital and childhood onset autosomal recessive deafness. Nat. Genet. 27, 59-63 https://doi.org/10.1038/83768
  18. Sonnhammer, E. L., von Heijne, G., and Krogh, A. (1998) A hidden Markov model for predicting transmembrane helices in protein sequences. Proc. Int. Conf. Intell. Syst. Mol. Biol. 6, 175-182
  19. Wallrapp, C., Hahnel, S., Muller-Pillasch, F., Burghardt, B., Iwamura, T., et al. (2000) A novel transmembrane serine protease (TMPRSS3) overexpressed in pancreatic cancer. Cancer Res. 60, 2602-2606
  20. Wattenhofer, M., Di Iorio, M. V., Rabionet, R., Dougherty, L., Pampanos, A., et al. (2002) Mutations in the TMPRSS3 gene are a rare cause of childhood nonsyndromic deafness in Caucasian patients. J. Mol. Med. 80, 124-131 https://doi.org/10.1007/s00109-001-0310-6
  21. Yamaguchi, N., Okui, A., Yamada, T., Nakazato, H., and Mitsui, S. (2002) Spinesin/TMPRSS5, a novel transmembrane serine protease, cloned from human spinal cord. J. Biol. Chem. 277, 6806-6812 https://doi.org/10.1074/jbc.M103645200