Table 2.
Membrane-anchored serine proteases – roles in human disease
| Protease | Abnormality | Role in disease | References |
|---|---|---|---|
| Prostasin | Over-expressed in lung epithelium of cystic fibrosis patients | May contribute to pathogenesis of cystic fibrosis by increasing fluid clearance | (Myerburg et al., 2008, Planes et al., 2010) |
| Increased soluble prostasin detect in urine in hypertensive patients | May have a role in development of high blood pressure | (Maekawa et al., 2009, Zhu et al., 2008) | |
| Over-activity in colonic epithelium caused by loss of inhibitor function | Implicated role in fluid secretion in congenital sodium diarrhea | (Faller et al., 2014) | |
| Testisin | Aberrant expression in advanced stage ovarian cancer | May promote tumor growth and metastasis | (Shigemasa et al., 2000, Tang et al., 2005) |
| Lost in male germ cell tumors | Unknown | (Kempkensteffen et al., 2006) | |
| HAT | Increased expression and shedding into airway fluids | Occurs in patients with inflammatory airway diseases such as asthma, function is unknown | (Yasuoka et al., 1997) |
| DESC1 | Lost in head and neck squamous cell carcinoma | Unknown | (Lang and Schuller, 2001, Sedghizadeh et al., 2006) |
| HATL-5 | Significantly decreased in cervical, esophageal, and head and neck carcinomas | Unknown | (Miller et al., 2014) |
| Hepsin | Increased expression in human prostate cancers which correlates with disease severity | Increases prostate cancer progression and metastasis in mouse models | (Wu and Parry, 2007) |
| TMPRSS2 | Frequent gene fusions between the promotor of TMPRSS2 and the ERG protooncogene and related transcription factors in prostate cancers | Androgen responsive elements in TMPRSS2 promotor drive expression of ERG transcription factor to promote prostate cancer progression | (Tomlins et al., 2005, Yu et al., 2010) |
| TMPRSS3 | Point mutations that inhibit TMPRSS3 auto-activation blocking its activity | Causes non-syndromic autosomal recessive deafness | (Lee et al., 2003, Scott et al., 2001, Wattenhofer et al., 2002) |
| TMPRSS4 | Over-expressed in epithelial carcinomas of diverse origins | May have a role in tumor progression | (Choi et al., 2008) |
| TMPRSS5 | Point mutation that inactivates TMPRSS5 | Associated with human deafness | (Guipponi et al., 2008) |
| Enteropeptidase | Intestinal deficiency caused by point mutations | Failure to thrive due to reduced digestive function | (Holzinger et al., 2002) |
| Matriptase | Mutations resulting in an inactive protease | ARIH, a rare human skin disease with ichthyosis and hair follicle defects | (Avrahami et al., 2008, Basel-Vanagaite et al., 2007, Desilets et al., 2008, Lee et al., 2007) |
| Expression downregulated in inflammatory bowel diseases | May contribute to loss of intestinal barrier function and disease pathogenesis | (Kosa et al., 2012, Netzel-Arnett et al., 2012) | |
| Reduced expression in salivary gland epithelium | Causes loss of secretory cell function, contribute to pathogenesis of Sjogren's syndrome | (Yin et al., 2014) | |
| Over-expressed in epithelial carcinomas of diverse origins | Possible role in tumor progression | (List, 2009) | |
| Matriptase-2 | Mutations that affect protease expression and activation | Causal factor in familial iron-refractory iron deficiency anemia | (Finberg et al., 2008, Guillem et al., 2008, Melis et al., 2008) |
| Corin | Polymorphisms that cause reduced protease activity due to decreased zymogen activation | Associated with hypertension and cardiac hypertrophy, worse clinical outcome in patients with heart failure | (Dries et al., 2005, Rame et al., 2007, Rame et al., 2009, Wang et al., 2008) |
| Mutations and reduced expression and in pregnant uterus | May have causal role in the development of pre-eclampsia | (Cui et al., 2012) |