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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).

Accession Number:P57727
Protein Name:Transmembrane protease serine 3
Length:454
Molecular Weight:49405.00
Species:Homo sapiens (Human) [9606]
Number of TMSs:1
Location1 / Topology2 / Orientation3: Endoplasmic reticulum membrane1 / Single-pass type II membrane protein2
Substrate

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FASTA formatted sequence
1:	MGENDPPAVE APFSFRSLFG LDDLKISPVA PDADAVAAQI LSLLPLKFFP IIVIGIIALI 
61:	LALAIGLGIH FDCSGKYRCR SSFKCIELIA RCDGVSDCKD GEDEYRCVRV GGQNAVLQVF 
121:	TAASWKTMCS DDWKGHYANV ACAQLGFPSY VSSDNLRVSS LEGQFREEFV SIDHLLPDDK 
181:	VTALHHSVYV REGCASGHVV TLQCTACGHR RGYSSRIVGG NMSLLSQWPW QASLQFQGYH 
241:	LCGGSVITPL WIITAAHCVY DLYLPKSWTI QVGLVSLLDN PAPSHLVEKI VYHSKYKPKR 
301:	LGNDIALMKL AGPLTFNEMI QPVCLPNSEE NFPDGKVCWT SGWGATEDGA GDASPVLNHA 
361:	AVPLISNKIC NHRDVYGGII SPSMLCAGYL TGGVDSCQGD SGGPLVCQER RLWKLVGATS 
421:	FGIGCAEVNK PGVYTRVTSF LDWIHEQMER DLKT