Table 1.
Membrane-anchored serine proteases – physiological functions learnt through protease deficiency
| Protease | Function | Implicated substrate | References |
|---|---|---|---|
| GPI-anchored | |||
| Prostasin | Maintenance of epidermal barrier function | Unknown | (Frateschi et al., 2012, Leyvraz et al., 2005, Peters et al., 2014) |
| Regulation of ENaC-mediated fluid clearance in lung and colon epithelium | ENaC-γ subunit | (Frateschi et al., 2012, Malsure et al., 2014, Planes et al., 2010) | |
| Regulation of hepatic insulin sensitivity by cleavage and inactivation of TLR-4 | Toll-like receptor-4 (TLR-4) | (Uchimura et al., 2014) | |
| Testisin | Involved in sperm cell maturation and fertilizing ability | Unknown | (Aimes et al., 2003, Inoue et al., 1998, Netzel-Arnett et al., 2009, Yamashita et al., 2008) |
| Type II | |||
| HAT/DESC subfamily | |||
| HAT | Unknown. Not required for development, long-term health or survival in mice | Unknown | (Bertram et al., 2012, Iwakiri et al., 2004, Takahashi et al., 2001, Yamaoka et al., 1998) |
| HATL-1 | Unknown. Not required for development, long-term health or survival in mice | Unknown | (Faller et al., 2014, Kam et al., 2009, Sales et al., 2011) |
| Hepsin/TMPRSS subfamily | |||
| Hepsin | Important for hearing in mice, where it has a role in cochlear development in inner ear | Unknown | (Faller et al., 2014, Guipponi et al., 2007, Kurachi et al., 1994, Tsuji et al., 1991) |
| Maintenance of liver structural homeostasis in mice | Pro-HGF | (Hsu et al., 2012) | |
| TMPRSS2 | Unknown. Not required for development, long-term health, fertility or survival in mice | Unknown | (Faller et al., 2014, Jacquinet et al., 2001, Kim et al., 2006) |
| TMPRSS3 | Mediates normal hearing in humans. Shown to be critical for cochlear hair cell survival in murine model of deficiency | Unknown | (Fasquelle et al., 2011, Guipponi et al., 2008, Lee et al., 2013, Molina et al., 2013) |
| TMPRSS5 | Mediates normal hearing in humans | Unknown | (Guipponi et al., 2008, Yamaguchi et al., 2002) |
| Enteropeptidase | Critical for digestion of dietary proteins. Initiates a proteolytic cascade that results in the activation of several intestinal proteases | Trypsinogen | (Haworth et al., 1971, Zheng et al., 2009) |
| Matriptase subfamily | |||
| Matriptase | Global role in maintenance of epidermal and epithelial barrier function and homeostasis. | Unknown | (List et al., 2002, List et al., 2009, Yin et al., 2014) |
| Matriptase-2 | Essential regulator of iron homeostasis that prevents iron deficiency anemia | Hemojuvelin | (Du et al., 2008, Folgueras et al., 2008, Truksa et al., 2009) |
| Corin subfamily | |||
| Corin | Regulates systemic salt and water balance to prevent hypertension and cardiac hypertrophy | Pro-ANP, pro-BNP | (Chan et al., 2005, Rame et al., 2009, Wang et al., 2008) |