TMPRSS2 [H4]

Transmembrane protease serine 2 (TMPRSS2) or Serine protease 10, is encoded by the TMPRSS2 or PRSS10 gene in human. TMPRSS2 is a single-pass type II membrane protein of the peptidase S1 family that is shown to proteolytically cleave and activate the viral spike glycoproteins, which facilitate virus-cell membrane fusions. It is shown to facilitate human SARS coronavirus (SARS-CoV) infection via two independent mechanisms, proteolytic cleavage of ACE2 that promotes viral uptake and cleavage of coronavirus spike glycoprotein, which activates the glycoprotein for cathepsin L-independent host cell entry. TMPRSS2 is highly expressed in the prostate tissue and lower expression levels are observed in the epithelia of the colon, stomach, epididymis and breast tissue. Some expression has also been reported in pancreatic acini, hepatic bile ducts, testicular Leydig cells and the kidney. Its expression levels are significantly elevated in both neoplastic prostate and in the epithelium of prostatic hyperplasia. TMPRSS2 has a cytoplasmic domain (aa 1-84), a transmembrane domain (aa 85-105), and an extracellular domain (aa 106-492). Its peptidase S1 domain is localized to amino acids 256-489. It is reported to be proteolytically processed by an autocatalytic mechanism, generating the transmembrane protease serine 2 non-catalytic chain (1-255) and the transmembrane protease serine 2 catalytic chain (256-492). Two isoforms of TMPRSS2 have been described that are produced by alternative splicing.