Gene Symbol: Prss8
Description: protease, serine 8 (prostasin)
Alias: 2410039E18Rik, AI313909, C79772, CAP1, mCAP1, prostasin, channel activating protease 1, serine protease 8
Species: mouse
Products:     Prss8

Top Publications

  1. Rubera I, Meier E, Vuagniaux G, Mérillat A, Beermann F, Rossier B, et al. A conditional allele at the mouse channel activating protease 1 (Prss8) gene locus. Genesis. 2002;32:173-6 pubmed
  2. Vuagniaux G, Vallet V, Jaeger N, Hummler E, Rossier B. Synergistic activation of ENaC by three membrane-bound channel-activating serine proteases (mCAP1, mCAP2, and mCAP3) and serum- and glucocorticoid-regulated kinase (Sgk1) in Xenopus Oocytes. J Gen Physiol. 2002;120:191-201 pubmed
    ..of ENaC-mediated sodium transport (I(Na)) by a GPI-anchored serine protease (mouse channel-activating protein, mCAP1) that was isolated from a cortical collecting duct cell line derived from mouse kidney...
  3. Netzel Arnett S, Currie B, Szabo R, Lin C, Chen L, Chai K, et al. Evidence for a matriptase-prostasin proteolytic cascade regulating terminal epidermal differentiation. J Biol Chem. 2006;281:32941-5 pubmed
    Recent gene ablation studies in mice have shown that matriptase, a type II transmembrane serine protease, and prostasin, a glycosylphosphatidylinositol-anchored membrane serine protease, are both required for processing of the epidermis-..
  4. Camerer E, Barker A, Duong D, Ganesan R, Kataoka H, Cornelissen I, et al. Local protease signaling contributes to neural tube closure in the mouse embryo. Dev Cell. 2010;18:25-38 pubmed publisher
    ..Among these, matriptase activated Par2 with picomolar potency, and hepsin and prostasin activated matriptase...
  5. Verghese G, Tong Z, Bhagwandin V, Caughey G. Mouse prostasin gene structure, promoter analysis, and restricted expression in lung and kidney. Am J Respir Cell Mol Biol. 2004;30:519-29 pubmed
    Human prostasin is a membrane-anchored serine peptidase hypothesized to regulate lung epithelial sodium transport. It belongs to a unique family of genes on chromosome 16p11.2/13.3...
  6. Chen L, Wang C, Chen M, Marcello M, Chao J, Chao L, et al. Prostasin attenuates inducible nitric oxide synthase expression in lipopolysaccharide-induced urinary bladder inflammation. Am J Physiol Renal Physiol. 2006;291:F567-77 pubmed
    b>Prostasin is a glycosylphosphatidylinositol-anchored serine protease, with epithelial sodium channel activation and tumor invasion suppression activities. We identified the bladder as an expression site of prostasin...
  7. Wakida N, Kitamura K, Tuyen D, Maekawa A, Miyoshi T, Adachi M, et al. Inhibition of prostasin-induced ENaC activities by PN-1 and regulation of PN-1 expression by TGF-beta1 and aldosterone. Kidney Int. 2006;70:1432-8 pubmed
    b>Prostasin has been shown to regulate sodium handling in the kidney. Recently, a serine protease inhibitor, protease nexin-1 (PN-1), was identified as an endogenous inhibitor for prostasin...
  8. List K, Currie B, Scharschmidt T, Szabo R, Shireman J, Molinolo A, et al. Autosomal ichthyosis with hypotrichosis syndrome displays low matriptase proteolytic activity and is phenocopied in ST14 hypomorphic mice. J Biol Chem. 2007;282:36714-23 pubmed
    ..reduced proteolytic activity toward small molecule substrates, as well as toward its candidate epidermal target, prostasin. To further investigate the possible contribution of low matriptase activity to ARIH, we generated an ST14 ..
  9. Szabo R, Hobson J, Christoph K, Kosa P, List K, Bugge T. Regulation of cell surface protease matriptase by HAI2 is essential for placental development, neural tube closure and embryonic survival in mice. Development. 2009;136:2653-63 pubmed publisher
    ..This study indicates that unregulated matriptase-dependent cell surface proteolysis can cause a diverse array of abnormalities in mammalian development. ..

More Information


  1. Szabo R, Uzzun Sales K, Kosa P, Shylo N, Godiksen S, Hansen K, et al. Reduced prostasin (CAP1/PRSS8) activity eliminates HAI-1 and HAI-2 deficiency-associated developmental defects by preventing matriptase activation. PLoS Genet. 2012;8:e1002937 pubmed publisher
    ..Hypomorphic mutations in Prss8, encoding the GPI-anchored serine protease, prostasin (CAP1, PRSS8), restored placentation and normal development of HAI-1-deficient embryos and prevented early ..
  2. Planes C, Randrianarison N, Charles R, Frateschi S, Cluzeaud F, Vuagniaux G, et al. ENaC-mediated alveolar fluid clearance and lung fluid balance depend on the channel-activating protease 1. EMBO Mol Med. 2010;2:26-37 pubmed publisher
    ..The membrane-bound channel-activating protease 1 (CAP1/Prss8) activates ENaC in vitro in various expression systems...
  3. Vuagniaux G, Vallet V, Jaeger N, Pfister C, Bens M, Farman N, et al. Activation of the amiloride-sensitive epithelial sodium channel by the serine protease mCAP1 expressed in a mouse cortical collecting duct cell line. J Am Soc Nephrol. 2000;11:828-34 pubmed
    ..isolated serine protease from Xenopus, xCAP1 (channel activating protease), a novel full-length serine protease (mCAP1), has been isolated and characterized...
  4. Frateschi S, Keppner A, Malsure S, Iwaszkiewicz J, Sergi C, Mérillat A, et al. Mutations of the serine protease CAP1/Prss8 lead to reduced embryonic viability, skin defects, and decreased ENaC activity. Am J Pathol. 2012;181:605-15 pubmed publisher
    CAP1/Prss8 is a membrane-bound serine protease involved in the regulation of several different effectors, such as the epithelial sodium channel ENaC, the protease-activated receptor PAR2, the tight junction proteins, and the profilaggrin ..
  5. List K, Hobson J, Molinolo A, Bugge T. Co-localization of the channel activating protease prostasin/(CAP1/PRSS8) with its candidate activator, matriptase. J Cell Physiol. 2007;213:237-45 pubmed
    b>Prostasin (CAP1/PRSS8) is a glycosylphosphatidylinositol-anchored membrane serine protease believed to be critical for the regulation of epithelial sodium channel (ENaC) activity...
  6. Spacek D, Perez A, Ferranti K, Wu L, Moy D, Magnan D, et al. The mouse frizzy (fr) and rat 'hairless' (frCR) mutations are natural variants of protease serine S1 family member 8 (Prss8). Exp Dermatol. 2010;19:527-32 pubmed publisher
    ..frizzy (fr) and rat 'hairless' (fr(CR)) mutations are natural variants of protease serine S1 family member 8 (Prss8). Experimental Dermatology 2010; 19: 527-532...
  7. Fan B, Brennan J, Grant D, Peale F, Rangell L, Kirchhofer D. Hepatocyte growth factor activator inhibitor-1 (HAI-1) is essential for the integrity of basement membranes in the developing placental labyrinth. Dev Biol. 2007;303:222-30 pubmed
    ..and extracellular serine proteases involved in tissue remodeling and tumorigenesis, such as HGFA, matriptase, prostasin and hepsin. We generated HAI-1 deficient mice, which died in utero due to placental defects...
  8. Andreasen D, Vuagniaux G, Fowler Jaeger N, Hummler E, Rossier B. Activation of epithelial sodium channels by mouse channel activating proteases (mCAP) expressed in Xenopus oocytes requires catalytic activity of mCAP3 and mCAP2 but not mCAP1. J Am Soc Nephrol. 2006;17:968-76 pubmed
    Mouse channel activating proteases 1, 2, and 3 (mCAP1, mCAP2, and mCAP3) were described recently as regulators of the epithelial sodium channel (ENaC)...
  9. Narikiyo T, Kitamura K, Adachi M, Miyoshi T, Iwashita K, Shiraishi N, et al. Regulation of prostasin by aldosterone in the kidney. J Clin Invest. 2002;109:401-8 pubmed
    b>Prostasin is a serine protease present in mammalian urine that increases the activity of the epithelial sodium channel (ENaC) when the two are coexpressed in Xenopus oocytes...
  10. Leyvraz C, Charles R, Rubera I, Guitard M, Rotman S, Breiden B, et al. The epidermal barrier function is dependent on the serine protease CAP1/Prss8. J Cell Biol. 2005;170:487-96 pubmed serine protease (CAP) 1 (also termed protease serine S1 family member 8 [Prss8] and prostasin) in skin, and these mice died within 60 h after birth...
  11. Buzza M, Johnson T, Conway G, Martin E, Mukhopadhyay S, Shea Donohue T, et al. Inflammatory cytokines down-regulate the barrier-protective prostasin-matriptase proteolytic cascade early in experimental colitis. J Biol Chem. 2017;292:10801-10812 pubmed publisher
    ..barrier-protective activity is linked with the glycosylphosphatidylinositol (GPI)-anchored serine protease prostasin, which is a co-factor for matriptase zymogen activation...
  12. Hummler E, Dousse A, Rieder A, Stehle J, Rubera I, Osterheld M, et al. The channel-activating protease CAP1/Prss8 is required for placental labyrinth maturation. PLoS ONE. 2013;8:e55796 pubmed publisher
    The serine protease CAP1/Prss8 is crucial for skin barrier function, lung alveolar fluid clearance and has been unveiled as diagnostic marker for specific cancer types...
  13. Bisaillon J, Radden L, Szabo E, Hughes S, Feliciano A, Nesta A, et al. The retarded hair growth (rhg) mutation in mice is an allele of ornithine aminotransferase (Oat). Mol Genet Metab Rep. 2014;1:378-390 pubmed
  14. Gong Y, Yu M, Yang J, Gonzales E, Perez R, Hou M, et al. The Cap1-claudin-4 regulatory pathway is important for renal chloride reabsorption and blood pressure regulation. Proc Natl Acad Sci U S A. 2014;111:E3766-74 pubmed publisher
    ..claudin-4-mediated chloride conductance can be regulated endogenously by a protease-channel-activating protease 1 (cap1). Mechanistically, cap1 regulates claudin-4 intercellular interaction and membrane stability...
  15. Carattino M, Mueller G, Palmer L, Frindt G, Rued A, Hughey R, et al. Prostasin interacts with the epithelial Na+ channel and facilitates cleavage of the γ-subunit by a second protease. Am J Physiol Renal Physiol. 2014;307:F1080-7 pubmed publisher
    ..For example, coexpression of prostasin with ENaC increases both channel function and cleavage at the γRKRK186 site...
  16. Friis S, Madsen D, Bugge T. Distinct Developmental Functions of Prostasin (CAP1/PRSS8) Zymogen and Activated Prostasin. J Biol Chem. 2016;291:2577-82 pubmed publisher
    The membrane-anchored serine prostasin (CAP1/PRSS8) is essential for barrier acquisition of the interfollicular epidermis and for normal hair follicle development. Consequently, prostasin null mice die shortly after birth...
  17. Wallace M, MacSwiney F. A major gene controlling warfarin-resistance in the house mouse. J Hyg (Lond). 1976;76:173-81 pubmed
    ..The adaptive significance of the finding is discussed, as also are reports of certain other mutants in wild populations of mice. ..
  18. MacSwiney F, Wallace M. Genetics of warfarin-resistance in house mice of three separate localities. J Hyg (Lond). 1978;80:69-75 pubmed
    ..Questions are posed as to the adaptive significance of the phenomena, and the way in which they work, in the patchwork of warfarin baited and unbaited areas in this country. ..
  19. Verghese G, Gutknecht M, Caughey G. Prostasin regulates epithelial monolayer function: cell-specific Gpld1-mediated secretion and functional role for GPI anchor. Am J Physiol Cell Physiol. 2006;291:C1258-70 pubmed
    b>Prostasin, a trypsinlike serine peptidase, is highly expressed in prostate, kidney, and lung epithelia, where it is bound to the cell surface, secreted, or both...
  20. Svenningsen P, Uhrenholt T, Palarasah Y, Skjødt K, Jensen B, Skøtt O. Prostasin-dependent activation of epithelial Na+ channels by low plasmin concentrations. Am J Physiol Regul Integr Comp Physiol. 2009;297:R1733-41 pubmed publisher
    ..Biotin-label transfer showed that plasmin interacted with the GPI-anchored protein prostasin on M-1 cells and that plasmin cleaved prostasin...
  21. Peters D, Szabo R, Friis S, Shylo N, Uzzun Sales K, Holmbeck K, et al. The membrane-anchored serine protease prostasin (CAP1/PRSS8) supports epidermal development and postnatal homeostasis independent of its enzymatic activity. J Biol Chem. 2014;289:14740-9 pubmed publisher
    The membrane-anchored serine protease prostasin (CAP1/PRSS8) is part of a cell surface proteolytic cascade that is essential for epithelial barrier formation and homeostasis...
  22. Szabo R, Peters D, Kosa P, Camerer E, Bugge T. Regulation of feto-maternal barrier by matriptase- and PAR-2-mediated signaling is required for placental morphogenesis and mouse embryonic survival. PLoS Genet. 2014;10:e1004470 pubmed publisher
    ..redundant protease signaling pathways that include the membrane-anchored serine proteases, matriptase and prostasin, and the G protein-coupled receptor PAR-2 that mediate the establishment of a functional feto-maternal barrier...
  23. Ahearn K, Akkouris G, Berry P, Chrissluis R, Crooks I, Dull A, et al. The Charles River "hairless" rat mutation maps to chromosome 1: allelic with fuzzy and a likely orthologue of mouse frizzy. J Hered. 2002;93:210-3 pubmed
    ..We suggest that the CR hairless rat mutation and fuzzy be renamed frizzy-Charles River (fr(CR)) and frizzy-Harlan (fr(H)), respectively, to reflect their likely orthology with the mouse fr mutation. ..
  24. Crisante G, Battista L, Iwaszkiewicz J, Nesca V, Mérillat A, Sergi C, et al. The CAP1/Prss8 catalytic triad is not involved in PAR2 activation and protease nexin-1 (PN-1) inhibition. FASEB J. 2014;28:4792-805 pubmed publisher
    ..The catalytically inactive serine protease CAP1/Prss8, when ectopically expressed in the mouse, retained the ability to induce skin disorders as well as its ..
  25. Szabo R, Lantsman T, Peters D, Bugge T. Delineation of proteolytic and non-proteolytic functions of the membrane-anchored serine protease prostasin. Development. 2016;143:2818-28 pubmed publisher
    The membrane-anchored serine proteases prostasin (PRSS8) and matriptase (ST14) initiate a cell surface proteolytic pathway essential for epithelial function...
  26. Brunati M, Perucca S, Han L, Cattaneo A, Consolato F, Andolfo A, et al. The serine protease hepsin mediates urinary secretion and polymerisation of Zona Pellucida domain protein uromodulin. elife. 2015;4:e08887 pubmed publisher
  27. Friis S, Sales K, Schafer J, Vogel L, Kataoka H, Bugge T. The protease inhibitor HAI-2, but not HAI-1, regulates matriptase activation and shedding through prostasin. J Biol Chem. 2014;289:22319-32 pubmed publisher
    The membrane-anchored serine proteases, matriptase and prostasin, and the membrane-anchored serine protease inhibitors, hepatocyte growth factor activator inhibitor (HAI)-1 and HAI-2, are critical effectors of epithelial development and ..
  28. Malsure S, Wang Q, Charles R, Sergi C, Perrier R, Christensen B, et al. Colon-specific deletion of epithelial sodium channel causes sodium loss and aldosterone resistance. J Am Soc Nephrol. 2014;25:1453-64 pubmed publisher
    ..Here, we investigated the importance of ENaC and its positive regulator channel-activating protease 1 (CAP1/Prss8) in colon...
  29. Ashby B. Co-expression of prostaglandin receptors with opposite effects: a model for homeostatic control of autocrine and paracrine signaling. Biochem Pharmacol. 1998;55:239-46 pubmed
    ..The mechanism is relevant to other autocrine and paracrine mediators including neurotransmitters, which reach transiently high concentrations in the synaptic cleft. ..
  30. Paul E, Badal R, Thompson D, Magnan D, Soucy F, Khan I, et al. The mouse frizzy mutation (fr) maps between D7Csu5 and D7Mit165. Exp Dermatol. 2008;17:640-4 pubmed publisher
    ..Further characterization of regional recombinants for sequence-level polymorphisms should allow sufficient refinement of fr's location to facilitate an eventual molecular assignment for this classical mutation. ..
  31. Shuto T, Kamei S, Nohara H, Fujikawa H, Tasaki Y, Sugahara T, et al. Pharmacological and genetic reappraisals of protease and oxidative stress pathways in a mouse model of obstructive lung diseases. Sci Rep. 2016;6:39305 pubmed publisher
    ..Thus, these assessments clarified that protease-antiprotease imbalance and oxidative stress are critical pathways that exacerbate the pulmonary phenotypes of C57/BL6J-?ENaC-Tg mice, consistent with the characteristics of human COPD/CF. ..
  32. Uchimura K, Hayata M, Mizumoto T, Miyasato Y, Kakizoe Y, Morinaga J, et al. The serine protease prostasin regulates hepatic insulin sensitivity by modulating TLR4 signalling. Nat Commun. 2014;5:3428 pubmed publisher
    ..Here we show that the serine protease prostasin (PRSS8) regulates hepatic insulin sensitivity by modulating Toll-like receptor 4 (TLR4)-mediated signalling...
  33. Metcalf D, Ng A, Baldwin T, Di Rago L, Mifsud S. Concordant mast cell and basophil production by individual hematopoietic blast colony-forming cells. Proc Natl Acad Sci U S A. 2013;110:9031-5 pubmed publisher
  34. Hogan M, King L, Sundberg J. Defects of pelage hairs in 20 mouse mutations. J Invest Dermatol. 1995;104:31S-32S pubmed
  35. Nagaike K, Kawaguchi M, Takeda N, Fukushima T, Sawaguchi A, Kohama K, et al. Defect of hepatocyte growth factor activator inhibitor type 1/serine protease inhibitor, Kunitz type 1 (Hai-1/Spint1) leads to ichthyosis-like condition and abnormal hair development in mice. Am J Pathol. 2008;173:1464-75 pubmed publisher
    ..It also inhibits matriptase and prostasin, both of which are membrane-bound serine proteinases that have critical roles in epidermal differentiation and ..