ExplorEnz: EC 3.4.21.122

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3.4.21.122

Accepted name:

transmembrane protease serine 2

Reaction:

The enzyme cleaves angiotensin-converting enzyme 2 (EC 3.4.17.23) and cleaves influenzea A and B virus and coronavirus spike glycoproteins at arginine residues.

Other name(s):

TMPRSS2 (gene name); epitheliasin

Comments:

The enzyme, present in mammalia, cleaves and inactivates EC 3.4.17.23, angiotensin-converting enzyme 2 (ACE2), at arginine residues in the region R697 to R716, which enhances influenza and coronavirus uptake [7]. The enzyme also cleaves and activates influenza and coronavirus spike glycoproteins and thus facilitates virus-cell membrane fusions. The cleavage of SARS-COV2 spike glycoprotein occurs between the S2 and S2′ site at SKPSKR/SFIEDL, while the cleavage of MERS-COV glycoprotein occurs at GSRSAR/SAIEDL.

Links to other databases:

BRENDA, EXPASY, Gene, KEGG, MetaCyc, MEROPS, PDB

References:

1.	Jacquinet, E., Rao, N.V., Rao, G.V. and Hoidal, J.R. Cloning, genomic organization, chromosomal assignment and expression of a novel mosaic serine proteinase: epitheliasin. FEBS Lett. 468 (2000) 93–100. [DOI] [PMID: 10683448]
2.	Jacquinet, E., Rao, N.V., Rao, G.V., Zhengming, W., Albertine, K.H. and Hoidal, J.R. Cloning and characterization of the cDNA and gene for human epitheliasin. Eur. J. Biochem. 268 (2001) 2687–2699. [DOI] [PMID: 11322890]
3.	Bottcher-Friebertshauser, E., Freuer, C., Sielaff, F., Schmidt, S., Eickmann, M., Uhlendorff, J., Steinmetzer, T., Klenk, H.D. and Garten, W. Cleavage of influenza virus hemagglutinin by airway proteases TMPRSS2 and HAT differs in subcellular localization and susceptibility to protease inhibitors. J. Virol. 84 (2010) 5605–5614. [DOI] [PMID: 20237084]
4.	Bertram, S., Glowacka, I., Muller, M.A., Lavender, H., Gnirss, K., Nehlmeier, I., Niemeyer, D., He, Y., Simmons, G., Drosten, C., Soilleux, E.J., Jahn, O., Steffen, I. and Pohlmann, S. Cleavage and activation of the severe acute respiratory syndrome coronavirus spike protein by human airway trypsin-like protease. J. Virol. 85 (2011) 13363–13372. [DOI] [PMID: 21994442]
5.	Bertram, S., Dijkman, R., Habjan, M., Heurich, A., Gierer, S., Glowacka, I., Welsch, K., Winkler, M., Schneider, H., Hofmann-Winkler, H., Thiel, V. and Pohlmann, S. TMPRSS2 activates the human coronavirus 229E for cathepsin-independent host cell entry and is expressed in viral target cells in the respiratory epithelium. J. Virol. 87 (2013) 6150–6160. [DOI] [PMID: 23536651]
6.	Abe, M., Tahara, M., Sakai, K., Yamaguchi, H., Kanou, K., Shirato, K., Kawase, M., Noda, M., Kimura, H., Matsuyama, S., Fukuhara, H., Mizuta, K., Maenaka, K., Ami, Y., Esumi, M., Kato, A. and Takeda, M. TMPRSS2 is an activating protease for respiratory parainfluenza viruses. J. Virol. 87 (2013) 11930–11935. [DOI] [PMID: 23966399]
7.	Heurich, A., Hofmann-Winkler, H., Gierer, S., Liepold, T., Jahn, O. and Pohlmann, S. TMPRSS2 and ADAM17 cleave ACE2 differentially and only proteolysis by TMPRSS2 augments entry driven by the severe acute respiratory syndrome coronavirus spike protein. J. Virol. 88 (2014) 1293–1307. [DOI] [PMID: 24227843]
8.	Limburg, H., Harbig, A., Bestle, D., Stein, D.A., Moulton, H.M., Jaeger, J., Janga, H., Hardes, K., Koepke, J., Schulte, L., Koczulla, A.R., Schmeck, B., Klenk, H.D. and Bottcher-Friebertshauser, E. TMPRSS2 is the major activating protease of influenza A virus in primary human airway cells and influenza B virus in human type II pneumocytes. J. Virol. 93 (2019) . [DOI] [PMID: 31391268]
9.	Bestle, D., Heindl, M.R., Limburg, H., Van Lam van, T., Pilgram, O., Moulton, H., Stein, D.A., Hardes, K., Eickmann, M., Dolnik, O., Rohde, C., Klenk, H.D., Garten, W., Steinmetzer, T. and Bottcher-Friebertshauser, E. TMPRSS2 and furin are both essential for proteolytic activation of SARS-CoV-2 in human airway cells. Life Sci Alliance 3 (2020) . [DOI] [PMID: 32703818]

[EC 3.4.21.122 created 2020]