This gene encodes a protein that belongs to the serine protease family. The encoded protein contains a type II transmembrane domain, a receptor class A domain, a scavenger receptor cysteine-rich domain and a protease domain. Serine proteases are known to be involved in many physiological and pathological processes. This gene was demonstrated to be up-regulated by androgenic hormones in prostate cancer cells and down-regulated in androgen-independent prostate cancer tissue. The protease domain of this protein is thought to be cleaved and secreted into cell media after autocleavage. The biological function of this gene is unknown.
TMPRSS2 protein's function in prostate carcinogenesis relies on overexpression of ETS transcription factors, such as ERG and ETV1, through gene fusion. TMPRSS2-ERG fusion gene is the most frequent, present in 40% - 80% of prostate cancers in humans. ERG overexpression contributes to development of androgen-independence in prostate cancer through disruption of androgen receptor signaling.
Some coronaviruses, e.g. both the SARS coronavirus of 2003 and the SARS-CoV-2 are activated by TMPRSS2 and can thus be inhibited by TMPRSS2 inhibitors. "SARS-CoV-2 uses the SARS-CoV receptor ACE2 for entry and the serine protease TMPRSS2 for S protein priming. A TMPRSS2 inhibitor approved for clinical use blocked entry and might constitute a treatment option." One experimental candidate as a TMPRSS2 inhibitor for potential use against both influenza and coronavirus infections in general, including those prior to the advent of COVID-19, is the OTC (in most countries) mucolytic cough medicine bromhexine, which is also being investigated as a possible treatment for COVID-19 itself as well.
^Paoloni-Giacobino A, Chen H, Peitsch MC, Rossier C, Antonarakis SE (September 1997). "Cloning of the TMPRSS2 gene, which encodes a novel serine protease with transmembrane, LDLRA, and SRCR domains and maps to 21q22.3". Genomics. 44 (3): 309–20. doi:10.1006/geno.1997.4845. PMID9325052.
Maruyama K, Sugano S (January 1994). "Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides". Gene. 138 (1–2): 171–4. doi:10.1016/0378-1119(94)90802-8. PMID8125298.
Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K, Suyama A, Sugano S (October 1997). "Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library". Gene. 200 (1–2): 149–56. doi:10.1016/S0378-1119(97)00411-3. PMID9373149.
Jacquinet E, Rao NV, Rao GV, Zhengming W, Albertine KH, Hoidal JR (May 2001). "Cloning and characterization of the cDNA and gene for human epitheliasin". European Journal of Biochemistry. 268 (9): 2687–99. doi:10.1046/j.1432-1327.2001.02165.x. PMID11322890.
Teng DH, Chen Y, Lian L, Ha PC, Tavtigian SV, Wong AK (June 2001). "Mutation analyses of 268 candidate genes in human tumor cell lines". Genomics. 74 (3): 352–64. doi:10.1006/geno.2001.6551. PMID11414763.
Soller MJ, Isaksson M, Elfving P, Soller W, Lundgren R, Panagopoulos I (July 2006). "Confirmation of the high frequency of the TMPRSS2/ERG fusion gene in prostate cancer". Genes, Chromosomes & Cancer. 45 (7): 717–9. doi:10.1002/gcc.20329. PMID16575875.