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Gene Review

PRSS8  -  protease, serine, 8

Homo sapiens

Synonyms: CAP1, Channel-activating protease 1, PROSTASIN, Prostasin, Serine protease 8
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Disease relevance of PRSS8


High impact information on PRSS8

  • To determine if aldosterone, one of the principal regulators of urinary Na reabsorption by the distal nephron, affects prostasin expression, we examined prostasin mRNA and protein in a cultured mouse cortical collecting duct cell line (M-1), whole rats, and patients with primary aldosteronism [4].
  • Regulation of prostasin by aldosterone in the kidney [4].
  • We used microarray technology to identify overexpressed genes for secretory proteins as potential serum biomarkers and selected prostasin, a serine protease normally secreted by the prostate gland, for further study [3].
  • RESULTS: Prostasin was detected by immunostaining more strongly in cancerous ovarian epithelial cells and stroma than in normal ovarian tissue [3].
  • CONCLUSIONS: Prostasin is overexpressed in epithelial ovarian cancer and should be investigated further as a screening or tumor marker, alone and in combination with CA 125 [3].

Chemical compound and disease context of PRSS8


Biological context of PRSS8

  • Human PRSS8 is a single-copy gene and has been localized on chromosome 16p11.2 by in situ hybridization [8].
  • The transcription initiation site of the PRSS8 gene has been defined at the G residue and its adjacent A residue in a sequence CTCATGACT, which is similar to an initiator element CTCANTCT [8].
  • We undertook a co-expression search using the Genesis Enterprise System Database from Gene Logic to identify prostasin inhibitors, on the assumption that prostasin and its natural inhibitors may have a similar gene expression pattern [9].
  • Soluble HAI-1B (sHAI-1B), comprising the entire extracellular domain, formed a 1:1 complex with purified prostasin in protein binding assays and inhibited prostasin enzymatic activity with an IC(50) of 66 +/- 15 nM [9].
  • In the presence of sub-inhibitory concentrations of zinc, the activity of prostasin increased several-fold and its substrate specificity was significantly altered in favor of a strong preference for histidine in positions P3 or P4 of the substrate [10].

Anatomical context of PRSS8

  • Prostasin is a trypsin-like serine protease that is glycosylphosphatidylinositol-anchored to the epithelial cell surface, from where it can be released in a soluble form [9].
  • Identification of hepatocyte growth factor activator inhibitor-1B as a potential physiological inhibitor of prostasin [9].
  • Moreover, when prostasin and HAI-1B were co-expressed in Chinese hamster ovary cells, complexes of prostasin with HAI-1B were detected on the cell membrane as well as in the culture medium, suggesting that preformed complexes were shed from the cell surface [9].
  • A recombinant human prostasin serine protease was expressed in several human cell lines [11].
  • Functional studies in the Xenopus oocyte expression system demonstrated that prostasin increased ENaC currents 60--80%, whereas TMPRSS2 markedly decreased ENaC currents and protein levels [12].

Associations of PRSS8 with chemical compounds

  • The absence of activity seen with substrates containing isoleucine in position P1' explains the inability of prostasin to autoactivate and suggests that prostasin proteolytic activity is regulated by an upstream protease [10].
  • The increase in blood pressure and plasma aldosterone levels as well as the reduction of plasma renin activity correlated with the expression of human prostasin transgene [2].
  • In summary, this work describes gamma-tryptases, which are novel members of chromosome 16p tryptase/prostasin gene families [13].
  • The purpose of this study was to analyze gene expression profiles in T cells stimulated with the native CAP-1 versus the agonist CAP1-6D peptide [14].
  • Liposome-mediated delivery of prostasin-expressing plasmid into mouse bladder produced similar attenuation effects on LPS-induced iNOS expression, while not affecting COX-2 or cytokine induction [15].

Regulatory relationships of PRSS8


Other interactions of PRSS8

  • Furthermore, prostasin was isolated with two major HAI-1/1B fragments (40 and 58 kDa) from OVCAR3 cell medium, demonstrating that prostasin.HAI-1/1B complexes are formed naturally [9].
  • A prostasin-preferred poly-basic cleavage site was found in the extracellular domains of the ENaC alpha- and beta-subunits, and may present a mechanism for prostasin activation [10].
  • Southern blot analysis, following a reverse transcription polymerase chain reaction, indicates that prostasin mRNA is expressed in prostate, liver, salivary gland, kidney, lung, pancreas, colon, bronchus, renal proximal tubular cells, and prostate carcinoma LNCaP cells [17].
  • Prostasin, denoted as PRSS8, is a newly identified human serine proteinase that shares high sequence identity with acrosin, plasma kallikrein, and hepsin (Yu et al., 1994, 1995) [8].
  • The structure of PRSS21 is very similar to the human prostasin gene (PRSS8) which maps nearby on 16p11.2, suggesting that these genes may have evolved through gene duplication [18].

Analytical, diagnostic and therapeutic context of PRSS8


  1. Prostasin, a membrane-anchored serine peptidase, regulates sodium currents in JME/CF15 cells, a cystic fibrosis airway epithelial cell line. Tong, Z., Illek, B., Bhagwandin, V.J., Verghese, G.M., Caughey, G.H. Am. J. Physiol. Lung Cell Mol. Physiol. (2004) [Pubmed]
  2. Adenovirus-mediated human prostasin gene delivery is linked to increased aldosterone production and hypertension in rats. Wang, C., Chao, J., Chao, L. Am. J. Physiol. Regul. Integr. Comp. Physiol. (2003) [Pubmed]
  3. Prostasin, a potential serum marker for ovarian cancer: identification through microarray technology. Mok, S.C., Chao, J., Skates, S., Wong, K., Yiu, G.K., Muto, M.G., Berkowitz, R.S., Cramer, D.W. J. Natl. Cancer Inst. (2001) [Pubmed]
  4. Regulation of prostasin by aldosterone in the kidney. Narikiyo, T., Kitamura, K., Adachi, M., Miyoshi, T., Iwashita, K., Shiraishi, N., Nonoguchi, H., Chen, L.M., Chai, K.X., Chao, J., Tomita, K. J. Clin. Invest. (2002) [Pubmed]
  5. Phase I/II combined chemoimmunotherapy with carcinoembryonic antigen-derived HLA-A2-restricted CAP-1 peptide and irinotecan, 5-fluorouracil, and leucovorin in patients with primary metastatic colorectal cancer. Weihrauch, M.R., Ansén, S., Jurkiewicz, E., Geisen, C., Xia, Z., Anderson, K.S., Gracien, E., Schmidt, M., Wittig, B., Diehl, V., Wolf, J., Bohlen, H., Nadler, L.M. Clin. Cancer Res. (2005) [Pubmed]
  6. Long-term follow-up of patients with advanced ovarian carcinoma treated with debulking surgery and chemotherapy consisting of cisplatin, doxorubicin, and cyclophosphamide. Gynecologic Oncology Group of the Comprehensive Cancer Center. Wils, J.A. Oncology (1990) [Pubmed]
  7. Immunocytochemical localization of DJ-1 in human male reproductive tissue. Yoshida, K., Sato, Y., Yoshiike, M., Nozawa, S., Ariga, H., Iwamoto, T. Mol. Reprod. Dev. (2003) [Pubmed]
  8. Structure and chromosomal localization of the human prostasin (PRSS8) gene. Yu, J.X., Chao, L., Ward, D.C., Chao, J. Genomics (1996) [Pubmed]
  9. Identification of hepatocyte growth factor activator inhibitor-1B as a potential physiological inhibitor of prostasin. Fan, B., Wu, T.D., Li, W., Kirchhofer, D. J. Biol. Chem. (2005) [Pubmed]
  10. Biochemical characterization of prostasin, a channel activating protease. Shipway, A., Danahay, H., Williams, J.A., Tully, D.C., Backes, B.J., Harris, J.L. Biochem. Biophys. Res. Commun. (2004) [Pubmed]
  11. Prostasin is a glycosylphosphatidylinositol-anchored active serine protease. Chen, L.M., Skinner, M.L., Kauffman, S.W., Chao, J., Chao, L., Thaler, C.D., Chai, K.X. J. Biol. Chem. (2001) [Pubmed]
  12. Regulation of the epithelial sodium channel by serine proteases in human airways. Donaldson, S.H., Hirsh, A., Li, D.C., Holloway, G., Chao, J., Boucher, R.C., Gabriel, S.E. J. Biol. Chem. (2002) [Pubmed]
  13. Characterization of human gamma-tryptases, novel members of the chromosome 16p mast cell tryptase and prostasin gene families. Caughey, G.H., Raymond, W.W., Blount, J.L., Hau, L.W., Pallaoro, M., Wolters, P.J., Verghese, G.M. J. Immunol. (2000) [Pubmed]
  14. Differential gene expression profiles in a human T-cell line stimulated with a tumor-associated self-peptide versus an enhancer agonist peptide. Palena, C., Schlom, J., Tsang, K.Y. Clin. Cancer Res. (2003) [Pubmed]
  15. Prostasin attenuates inducible nitric oxide synthase expression in lipopolysaccharide-induced urinary bladder inflammation. Chen, L.M., Wang, C., Chen, M., Marcello, M.R., Chao, J., Chao, L., Chai, K.X. Am. J. Physiol. Renal Physiol. (2006) [Pubmed]
  16. Mechanisms of sterol regulatory element-binding protein-2 (SREBP-2) regulation of human prostasin gene expression. Chen, M., Chen, L.M., Chai, K.X. Biochem. Biophys. Res. Commun. (2006) [Pubmed]
  17. Molecular cloning, tissue-specific expression, and cellular localization of human prostasin mRNA. Yu, J.X., Chao, L., Chao, J. J. Biol. Chem. (1995) [Pubmed]
  18. Localization, expression and genomic structure of the gene encoding the human serine protease testisin. Hooper, J.D., Bowen, N., Marshall, H., Cullen, L.M., Sood, R., Daniels, R., Stuttgen, M.A., Normyle, J.F., Higgs, D.R., Kastner, D.L., Ogbourne, S.M., Pera, M.F., Jazwinska, E.C., Antalis, T.M. Biochim. Biophys. Acta (2000) [Pubmed]
  19. Prostasin is a novel human serine proteinase from seminal fluid. Purification, tissue distribution, and localization in prostate gland. Yu, J.X., Chao, L., Chao, J. J. Biol. Chem. (1994) [Pubmed]
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