8.A.131.1.1
The transmembrane protease serine system 3, TMPRSS3 (ECHOS1, TADG12, UNQ323/PRO382) of 454 aas and 1 very large hydrophobic N-terminal TMS. It is involved in activation of ENaC in the inner ear (Guipponi et al. 2002). The C-terminal half of the protein is homologous to part of the multidomain serine protease/channel protein with TC# 1.A.17.3.1, but no other protein in this latter family. A short sequence in the N-terminal region shows similarity with members of TC family 9.B.87.  Mutations in the gene encoding TMPRSS3 cause human hearing loss. Tang et al. 2019 investigate the role of TMPRSS3, showing that a defect leads to hair cell apoptosis without altering the development of hair cells and the formation of the mechanotransduction apparatus. Prior to degeneration, Tmprss3-KO hair cells show reduced numbers of BK channels and lower expression of genes encoding calcium ion-binding proteins, suggesting disruption in intracellular homeostasis. A proteolytically active TMPRSS3 was detected on cell membranes in addition to the ER of cells in inner ear organoids (Tang et al. 2019). TMPRSS3 regulates cell viability and apoptosis processes via regulation of the circ-Slc4a2, miR-182 and Akt cascade (Zhang et al. 2019).