PRSS8 explained

Prostasin is a protein that in humans is encoded by the PRSS8 gene.^{[1] [2] [3]}

This gene encodes a trypsinogen, which is a member of the trypsin family of serine proteases. This enzyme is highly expressed in prostate epithelia and is one of several proteolytic enzymes found in seminal fluid. The proprotein is cleaved to produce a light chain and a heavy chain which are associated by a disulfide bond. It is active on peptide linkages involving the carboxyl group of lysine or arginine.

The protein is implicated in epithelial sodium channel regulation^[4] and may help regulate a variety of tissue functions that involve a sodium channel.^[5]

High prostasin plasma levels may be associated with a higher risk for diabetes and death from cancer, especially in people with high blood sugar.^[6]

Further reading

• Yu JX, Chao L, Chao J . Prostasin is a novel human serine proteinase from seminal fluid. Purification, tissue distribution, and localization in prostate gland . The Journal of Biological Chemistry . 269 . 29 . 18843–8 . Jul 1994 . 10.1016/S0021-9258(17)32244-5 . 8034638 . free .
• Nelson PS, Gan L, Ferguson C, Moss P, Gelinas R, Hood L, Wang K . Molecular cloning and characterization of prostase, an androgen-regulated serine protease with prostate-restricted expression . Proceedings of the National Academy of Sciences of the United States of America . 96 . 6 . 3114–9 . Mar 1999 . 10077646 . 15904 . 10.1073/pnas.96.6.3114 . 1999PNAS...96.3114N . free .
• Chen LM, Skinner ML, Kauffman SW, Chao J, Chao L, Thaler CD, Chai KX . Prostasin is a glycosylphosphatidylinositol-anchored active serine protease . The Journal of Biological Chemistry . 276 . 24 . 21434–42 . Jun 2001 . 11274175 . 10.1074/jbc.M011423200 . free .
• Donaldson SH, Hirsh A, Li DC, Holloway G, Chao J, Boucher RC, Gabriel SE . Regulation of the epithelial sodium channel by serine proteases in human airways . The Journal of Biological Chemistry . 277 . 10 . 8338–45 . Mar 2002 . 11756432 . 10.1074/jbc.M105044200 . free .
• Wang C, Chao J, Chao L . Adenovirus-mediated human prostasin gene delivery is linked to increased aldosterone production and hypertension in rats . American Journal of Physiology. Regulatory, Integrative and Comparative Physiology . 284 . 4 . R1031-6 . Apr 2003 . 12626364 . 10.1152/ajpregu.00660.2002 .
• Colland F, Jacq X, Trouplin V, Mougin C, Groizeleau C, Hamburger A, Meil A, Wojcik J, Legrain P, Gauthier JM . Functional proteomics mapping of a human signaling pathway . Genome Research . 14 . 7 . 1324–32 . Jul 2004 . 15231748 . 442148 . 10.1101/gr.2334104 .
• Tong Z, Illek B, Bhagwandin VJ, Verghese GM, Caughey GH . Prostasin, a membrane-anchored serine peptidase, regulates sodium currents in JME/CF15 cells, a cystic fibrosis airway epithelial cell line . American Journal of Physiology. Lung Cellular and Molecular Physiology . 287 . 5 . L928-35 . Nov 2004 . 15246975 . 10.1152/ajplung.00160.2004 .
• Shipway A, Danahay H, Williams JA, Tully DC, Backes BJ, Harris JL . Biochemical characterization of prostasin, a channel activating protease . Biochemical and Biophysical Research Communications . 324 . 2 . 953–63 . Nov 2004 . 15474520 . 10.1016/j.bbrc.2004.09.123 .
• Leyvraz C, Charles RP, Rubera I, Guitard M, Rotman S, Breiden B, Sandhoff K, Hummler E . The epidermal barrier function is dependent on the serine protease CAP1/Prss8 . The Journal of Cell Biology . 170 . 3 . 487–96 . Aug 2005 . 16061697 . 2171460 . 10.1083/jcb.200501038 .
• Fan B, Wu TD, Li W, Kirchhofer D . Identification of hepatocyte growth factor activator inhibitor-1B as a potential physiological inhibitor of prostasin . The Journal of Biological Chemistry . 280 . 41 . 34513–20 . Oct 2005 . 16103126 . 10.1074/jbc.M502119200 . free .
• Chen M, Chen LM, Chai KX . Androgen regulation of prostasin gene expression is mediated by sterol-regulatory element-binding proteins and SLUG . The Prostate . 66 . 9 . 911–20 . Jun 2006 . 16541421 . 10.1002/pros.20325 . 23036264 . free .
• Rohan S, Tu JJ, Kao J, Mukherjee P, Campagne F, Zhou XK, Hyjek E, Alonso MA, Chen YT . Gene expression profiling separates chromophobe renal cell carcinoma from oncocytoma and identifies vesicular transport and cell junction proteins as differentially expressed genes . Clinical Cancer Research . 12 . 23 . 6937–45 . Dec 2006 . 17145811 . 10.1158/1078-0432.CCR-06-1268 . free .
• Chen M, Fu YY, Lin CY, Chen LM, Chai KX . Prostasin induces protease-dependent and independent molecular changes in the human prostate carcinoma cell line PC-3 . Biochimica et Biophysica Acta (BBA) - Molecular Cell Research . 1773 . 7 . 1133–40 . Jul 2007 . 17532063 . 1950849 . 10.1016/j.bbamcr.2007.04.013 .

Chen LM, Hatfield ML, Fu YY, Chai KX. Prostasin regulates iNOS and cyclin D1 expression by modulating protease-activated receptor-2 signaling in prostate epithelial cells. Prostate. 2009 Dec 1;69(16):1790-801. doi: 10.1002/pros.21030. PMID: 19670249.

Notes and References

1. Yu JX, Chao L, Ward DC, Chao J . Structure and chromosomal localization of the human prostasin (PRSS8) gene . Genomics . 32 . 3 . 334–40 . Mar 1996 . 8838796 . 10.1006/geno.1996.0127 . free .
2. Yu JX, Chao L, Chao J . Molecular cloning, tissue-specific expression, and cellular localization of human prostasin mRNA . The Journal of Biological Chemistry . 270 . 22 . 13483–9 . Jun 1995 . 7768952 . 10.1074/jbc.270.22.13483 . free .
3. Web site: Entrez Gene: PRSS8 protease, serine, 8.
4. Koda A, Wakida N, Toriyama K, Yamamoto K, Iijima H, Tomita K, Kitamura K . Urinary prostasin in humans: relationships among prostasin, aldosterone and epithelial sodium channel activity . Hypertension Research . 32 . 4 . 276–81 . Apr 2009 . 19262497 . 10.1038/hr.2009.6 . free .
5. Zhu H, Guo D, Li K, Yan W, Tan Y, Wang X, Treiber FA, Chao J, Snieder H, Dong Y . Prostasin: a possible candidate gene for human hypertension . American Journal of Hypertension . 21 . 9 . 1028–33 . Sep 2008 . 18583984 . 3812941 . 10.1038/ajh.2008.224 .
6. Bao X, Xu B, Muhammad IF, Nilsson PM, Nilsson J, Engström G . Plasma prostasin: a novel risk marker for incidence of diabetes and cancer mortality . Diabetologia . August 2022 . 65 . 10 . 1642–1651 . 35922613 . 10.1007/s00125-022-05771-w . 9477896 .