Transmembrane protease serine 4 (TMPRSS4)

Transmembrane protease serine 4 (TMPRSS4) is a type II transmembrane serine protease belonging to the serine protease family, encoded by the TMPRSS4 gene on human chromosome 11[5]. TMPRSS4 is anchored in the plasma membrane and contains several domains: an N-terminal segment, a transmembrane region, a low-density lipoprotein receptor class A (LDLRA) domain, a scavenger receptor cysteine-rich (SRCR) domain, and a C-terminal serine protease domain, which bears the catalytic activity[3]. This protease is implicated in a range of physiological and pathological processes, including facilitation of epithelial cell migration, potential promotion of epithelial-to-mesenchymal transition (EMT), regulation of tissue remodeling, and modulation of cell adhesion[1][5]. TMPRSS4 is found to be overexpressed in several cancers (serving as a poor prognostic biomarker), in fibrotic lung disease, and is critical in facilitating viral entry (e.g., SARS-CoV-2 infection of intestinal and respiratory epithelium)[2][3]. It is considered a promising but as-yet unvalidated therapeutic target in oncology, fibrotic disease, and infectious disease contexts due to emerging in silico and preclinical data on small-molecule and peptide inhibitors[3].

Other names

CAP2CAPH2Channel-activating protease 2Channel-activating serine protease 2Membrane-type serine protease 2MT-SP2Transmembrane serine protease 3Transmembrane protease serine 4 catalytic chain

Direct inhibition of serine protease activity (by competitive or allosteric inhibiting binding to the protease domain). Blockade of S protein cleavage and membrane fusion (for viral infection, e.g., SARS-CoV-2)[2][3]. Downregulation of EMT/partial EMT processes involved in tissue remodeling and malignancy[1][3].