TMPRSS2 is a 492 amino acid single-pass type II membrane protein. It contains a Serine protease domain (aa 255-492) of the S1 family, followed by a Scavenger receptor cysteine-rich domain (SRDR, aa 149-242) of group A; an LDL receptor class A (LDLRA, aa 113-148) domain forms a binding site for calcium; a predicted transmembrane domain (aa 84-106). Letters H, D and S in the serine protease domain indicate the position of the three catalytic residues histidine, aspartate and serine, respectively.

Multidomain structure of human TTSPs. Human TTSPs were grouped into four subfamilies based on similarity in domain structure and phylogenetic analysis of the serine protease domains, namely the matriptase, corin, hepsin/TMPRSS and HAT/DESC subfamilies. Consensus domains are shown below. Each diagram was drawn using the web-based SMART software (http://smart.embl-heidelberg.de) with TTSP amino acid sequences obtained from GenBank.

Abbreviations: CUB, Cls/Clr, urchin embryonic growth factor and bone morphogenic protein-1 domain; DESC1, differentially expressed squamous cell carcinoma gene 1; FRZ, frizzled domain; HAT, human airway trypsin-like protease; LDLA, low-density lipoprotein receptor domain class A; MAM, a meprin, A5 antigen and receptor protein phosphatase m domain; MSPL, mosaic serine protease long-form; Polyserase-1, polyserine protease-1; SEA, a single sea urchin sperm protein, enteropeptidase, agrin domain; SR, scavenger receptor cysteine-rich domain; TM, transmembrane domain. Letters H, D and S in the serine protease domain (active) indicate the position of the three catalytic residues histidine, aspartate and serine, respectively. Letter A in the serine protease domain (inactive) indicates a serine to alanine exchange.