TMPRSS4

TMPRSS4

A gene on chromosome 11q23.3 that encodes a putative serine protease thought to activate the epithelial sodium channel (ENaC).
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Proteolytic activation of seasonal human IAV HA occurs extracellularly or on the cell membrane in the airway by trypsin-type proteases, such as tryptase Clara, (19) mini-plasmin, (7) trypsin, (3) ectopic pancreatic trypsin, (4),(8),(10),(11),(21) porcine lung tryp tase, (22) TC30 (23) and type-II membrane bound proteases, human airway trypsin-like protease (HAT), transmembrane serine protease (TMPRSS)2 (24) and TMPRSS4 (25) (Table 1).
As outlined in this review, the knowledge gained within the last decades and the experience gained from the pandemic influenza A (H1N1) 2009 and HPAI outbreak greatly improved our understanding of the role of host cellular factors in the pathogenicity of IAV infection: (i) Several cell surface anchored trypsin-like serine proteases are candidates of HA-processing protease for seasonal human IAV, TMPRSS2, HAT and TMPRSS4, other than secreted HA-processing proteases in the airway, such as tryptase Clara, trypsin and mini-plasmin, and for HPAI viruses MSPL/ TMPRSS13 other than furin and PCs.
Comparison of proteases involved in HA processing Enzyme MW (kDa) MW (kDa) Optimal SDS-PAGE Non-reducing substrate condition (composition) Seasonal IAV Tryptase 30 180 (hexamer) QAR Clara Mini-plasmin 28 + 12 38 (heterodimer) QAR Ectopic 22 31 (monomer) EGR, anionic QGR trypsin I Mast cell 32-35 120 (tetramer) QAR tryptase Tryptase TC30 30 30 (monomer) SIQSR HAT 28 28 (monomer) FSR TMPRSS2 70 (32) 70 (32: GGR released form) (monomer) TMPRSS4 48 68 (monomer) QAR HPAI virus Furin/PC5/6 52.