TCDB is operated by the Saier Lab Bioinformatics Group
TCIDNameDomainKingdom/PhylumProtein(s)
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).

Eukaryota
Metazoa
TMPRSS3 of Homo sapiens
8.A.131.1.2









Serine protease 27-like protein of 321 aas and 1 N-terminal TMS.  This protein shows significant similarity with the TMEM106B protein with TC# 9.B.23.1.2.

Eukaryota
Metazoa
Serine protease 27 of Electrophorus electricus
8.A.131.1.3









Serine protease 55 of 369 aas and 1 TMS.

Eukaryota
Metazoa
Serine protease 55 of Neophocaena asiaeorientalis asiaeorientalis (Yangtze finless porpoise)
8.A.131.1.4









Suppressor of tumorigenicity 14 protein, ST-14 or St14, of 855 aas and one N-terminal TMS (Alef et al. 2009). Mitochondrial localization of St14-encoding transmembrane serine protease is involved in neural stem/progenitor cell bioenergetics through binding to the F0F1-ATP synthase complex (Fang et al. 2019).

Eukaryota
Metazoa
ST-14 of Homo sapiens
8.A.131.1.5









Kallikrein 3, KLK3, of 261 aas and 1 N-terminal TMS. It and TMPRSS2 (TC# 8.A.131.1.6) can be used for molecular lymph-node staging in prostate cancer patients undergoing prostatectomy (Lunger et al. 2020).

Eukaryota
Opisthokonta
KLK3 of Homo sapiens
8.A.131.1.6









TMPRSS2 of 492 aas and one TMS near the N-terminus. It and kallikrein 3, KLK3 (TC# 8.A.131.1.5) can be used for molecular lymph-node staging in prostate cancer patients undergoing prostatectomy (Lunger et al. 2020). Camostat mesylate is a potent inhibitor of the human transmembrane protease, serine 2 (TMPRSS2) and is under investigation for its effectiveness in COVID-19 patients. Its active metabolite is 4-(4-guanidinobenzoyloxy)phenylacetic acid (GBPA). OATP2B1 is inhibited by GBPA with an IC50 of 11 muM (Weiss et al. 2021). Although nafamostat and camostat have been identified as TMPRSS2 inhibitors, severe side effects such as cerebral hemorrhage, anaphylactoid reaction, and cardiac arrest shock greatly hamper their clinical use. Flupirtine, a selective neuronal potassium channel opener, is a potential TMPRSS2 inhibitor (Chen et al. 2021).

Eukaryota
Opisthokonta
TMPRSS2 of Homo sapiens
8.A.131.1.7









Transmembrane protease serine 11A, TMPRSS11A, ECRG1, HATL1, HESP, a Type II transmembrane serine proteases of 421 aas and one N-terminal TMS.  It may play a role in cellular senescence. Overexpression inhibits cell growth and induces G1 cell cycle arrest. It is expressed on the surface of airway epithelial cells and has been shown to cleave and activate spike proteins of the severe acute respiratory syndrome (SARS), SARS-2 and the Middle East respiratory syndrome (MERS) coronaviruses (CoVs). The activation cleavage of human TMPRSS11A is mediated by autocatalysis, and activation cleavage occurred before the protein reached the cell surface (Zhang et al. 2020). TMPRSS11a is an age-altered, tissue specific regulator of migration and wound healing (Fernandez et al. 2021).

 

Eukaryota
Opisthokonta
ECRG1 of Homo sapiens
8.A.131.1.8









Corin (CRN) or TMPRESS10 or atrial natriuretic peptide-converting enzyme of 1042 aas with an N-terminal TMS. See family description for details.

Eukaryota
Opisthokonta
Corin of Homo sapiens
8.A.131.1.9









Chmotrypsinogen-like protease of 263 aas and 1 N-terminal TMS.

Eukaryota
Opisthokonta
Chmotrypsin-like protease of Chrysochloris asiatica (Cape golden mole)
8.A.131.1.10









Transmembrane protease serine 4 isoform X1 of 433 aas and 1 N-terminal TMS.

Eukaryota
Opisthokonta
Protease of Physeter catodon (sperm whale)
8.A.131.1.11









Low-density lipoprotein receptor-related protein 1B isoform X1 of 4654 aas and 2 TMSs, N-terminal and near the C-terminus of the protein.

Eukaryota
Opisthokonta
Receptor and protease of Danio rerio (Zebrafish)
8.A.131.1.12









Hepsin, Hpn or IMPRESS1, of 417 aas and 1 N-terminal TMS. The N-glycan in the scavenger receptor cysteine-rich domain of hepsin promotes intracellular trafficking and cell surface expression (Sun et al. 2020). Hpn is a serine protease that cleaves extracellular substrates, and contributes to the proteolytic processing of growth factors, such as HGF and MST1/HGFL (Ganesan et al. 2011, Herter et al. 2005). It plays a role in cell growth and maintenance of cell morphology (Torres-Rosado et al. 1993), Ganesan et al. 2011), and also in the proteolytic processing of ACE2 (Heurich et al. 2014). It mediates the proteolytic cleavage of urinary UMOD that is required for UMOD polymerization (Brunati et al. 2015).

Eukaryota
Opisthokonta
Hpn of Homo sapiens