COVID-19 Spotlight: Human Transmembrane Serine Protease 2

Transmembrane Serine Protease 2 (also known as PRSS10; Serine protease 10) is a protease with a type II transmembrane domain that is involved in various physiological and pathological processes, including prostate cancer.¹ Androgenic hormones in prostate cancer cells have been shown to up-regulate TMPRSS2, but androgen-independent prostate cancer tissue has been shown to down-regulate it.² Although the biological function for TMPRSS2 has not yet been discovered,¹ this protein facilitates viral entry into host cells for the influenza virus, and several coronaviruses, including SARS-CoV-2.³

Several recent studies have looked at how angiotensin converting enzyme 2 (ACE2) helps facilitate infection by SARS-CoV-2, as well as previously, SARS-CoV.^4,5,6 However, priming of the viral spike protein by cleaving the S protein at S1/S2 and S2 sites by TMPRSS2 is a necessary initial step for entry into the cell.^3,4,7 The S protein cleavage allows for the fusing of viral and cellular membranes, engaging the ACE2 receptor for entry into the cell and subsequent infection.^3,4 Studies looking at TMPRSS2-deficient or TMPRSS2 knockout mice show that they appear to be healthy,⁸ suggesting that TMPRSS2 could be a more suitable and safe target than ACE2 for treatment or prevention of respiratory virus infections, including SARS-CoV-2.^3,7,9,10

Reddot Biotech is pleased to offer a Human Transmembrane Serine Protease 2 ELISA kit in both our traditional and Ready-To-Use formats. Our Human TMPRSS2 kits have a nanogram range (detection range 0.156-10ng/mL; sensitivity 0.056ng/mL) and are suitable for use with a wide variety of different sample types. For more information and to see the product manual, visit our product pages for RDR-TMPRSS2-Hu and RD-TMPRSS2-Hu. For any other questions, please feel free to contact us.

References and further reading:

1. TMPRSS2 transmembrane serine protease 2 [Homo sapiens (human)] - Gene - NCBI. (n.d.) Retrieved September 25, 2020, from http://www.ncbi.nlm.nih.gov/ge...;
2. Yu, J., Yu, J., Mani, R. S., Cao, Q., Brenner, C. J., Cao, X., ... & Gong, Y. (2010). An integrated network of androgen receptor, polycomb, and TMPRSS2-ERG gene fusions in prostate cancer progression. Cancer cell, 17(5), 443-454.
3. Bestle, D., Heindl, M. R., Limburg, H., Pilgram, O., Moulton, H., Stein, D. A., ... & Becker, S. (2020). TMPRSS2 and furin are both essential for proteolytic activation and spread of SARS-CoV-2 in human airway epithelial cells and provide promising drug targets. bioRxiv.
4. Hoffmann, M., Kleine-Weber, H., Schroeder, S., Krüger, N., Herrler, T., Erichsen, S., ... & Müller, M. A. (2020). SARS-CoV-2 cell entry depends on ACE2 and TMPRSS2 and is blocked by a clinically proven protease inhibitor. Cell.
5. Ou, X., Liu, Y., Lei, X., Li, P., Mi, D., Ren, L., ... & Xiang, Z. (2020). Characterization of spike glycoprotein of SARS-CoV-2 on virus entry and its immune cross-reactivity with SARS-CoV. Nature communications, 11(1), 1-12.
6. Walls, A. C., Park, Y. J., Tortorici, M. A., Wall, A., McGuire, A. T., & Veesler, D. (2020). Structure, function, and antigenicity of the SARS-CoV-2 spike glycoprotein. Cell.
7. Baughn, L. B., Sharma, N., Elhaik, E., Sekulic, A., Bryce, A. H., & Fonseca, R. (2020, September). Targeting TMPRSS2 in SARS-CoV-2 infection. In Mayo Clinic Proceedings (Vol. 95, No. 9, pp. 1989-1999). Elsevier.
8. Kim, T. S., Heinlein, C., Hackman, R. C., & Nelson, P. S. (2006). Phenotypic analysis of mice lacking the Tmprss2-encoded protease. Molecular and cellular biology, 26(3), 965-975.
9. Sakai, K., Ami, Y., Tahara, M., Kubota, T., Anraku, M., Abe, M., ... & Ainai, A. (2014). The host protease TMPRSS2 plays a major role in in vivo replication of emerging H7N9 and seasonal influenza viruses. Journal of virology, 88(10), 5608-5616.
10. Iwata-Yoshikawa, N., Okamura, T., Shimizu, Y., Hasegawa, H., Takeda, M., & Nagata, N. (2019). TMPRSS2 contributes to virus spread and immunopathology in the airways of murine models after coronavirus infection. Journal of virology, 93(6).
11. Matsuyama, S., Nao, N., Shirato, K., Kawase, M., Saito, S., Takayama, I., ... & Sakata, M. (2020). Enhanced isolation of SARS-CoV-2 by TMPRSS2-expressing cells. Proceedings of the National Academy of Sciences, 117(13), 7001-7003.