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Transmembrane protease, serine 2 (TMPRSS2) is a serine protease enzyme with an unclear physiological function. TMPRSS2 is essential for the cell entry of influenza viruses and coronaviruses, including SARS-CoV, SARS-CoV-2 and MERS. Expression of TMPRSS2 is androgen-regulated, and this protein has been linked to the development and metastasis of prostate cancer.
Transmembrane protease, serine 2 (TMPRSS2) is a serine protease with a type II transmembrane domain and an extracellular serine protease domain, which preferentially cleaves substrates at basic residues. TMPRSS2 is expressed in human bronchial epithelial cells, nasal goblet cells, small intestine epithelia, the prostate, gastrointestinal tract, kidneys and pancreas, with highest expression levels found in the prostate.The normal physiological role of TMPRSS2 is unknown, however its expression is regulated by androgens, and TMPRSS2 inhibitors such as Camostat (Cat. No. 3193), a broad spectrum protease inhibitor, are clinically approved for the treatment of pancreatitis.
Expression of TMPRSS2 is upregulated in high-grade prostate cancer, and also in the majority of metastases originating from prostate cancer. TMPRSS2 cleaves and activates hepatocyte growth factor (HGF), which regulates extracellular matrix (ECM) disruption, cancer cell invasion and metastasis of prostate cancer cells. In 40 - 80% of prostate cancers fusion of the TMPRRS2 gene with the neighboring EGR gene, encoding an ETS family transcription factor, leads to ERG overexpression and amplification of ERG-regulated genes. Experimental knockdown of TMPRSS2 overexpression in prostate cancer cells is associated with reduced metastatic potential. This indicates that TMPRSS2 is part of an androgen-regulated signaling cascade that promotes metastasis of prostate cancer cells.
TMPRSS2 in a key protein in the viral host cell entry mechanism of coronaviruses and influenza viruses, facilitating viral cell entry by cleavage of viral glycoproteins. In COVID-19, caused by SARS-CoV-2 infection, TMPRSS2 is co-expressed with ACE2 on human bronchial epithelial cells. Following binding to ACE2 by the viral spike 'S' protein, TMPRSS2 cleaves the S glycoprotein to facilitate entry of the virus into the cell. TMPRSS2 plays the same role following infection with other coronaviruses such as SARS-Cov and MERS. Additionally, TMPRSS2 plays a role in influenza virus infection; it cleaves and activates hemagglutinin (HA), which is essential for influenza virus infection in human airway epithelial cells.
TPMRSS2 knockout mice are protected against severe pathology and death following influenza virus infection, and show reduced SARS-CoV or MERS viral replication in the lungs. These mice also show altered infection spread patterns, suggesting that TMPRSS2 expression can affect the spread of coronaviruses and influenza.
Tocris offers the following scientific literature for TMPRSS2 to showcase our products. We invite you to request* your copy today!
*Please note that Tocris will only send literature to established scientific business / institute addresses.
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