CLONING OF THE TMPRSS2 GENE, WHICH ENCODES A NOVEL SERINE-PROTEASE WITH TRANSMEMBRANE, LDLRA, AND SRCR DOMAINS AND MAPS TO 21Q22.3

To contribute to the development of the transcription map of human chr omosome 21 (HC21), we have used exon trapping from pools of HC21-speci fic cosmids. Using selected trapped exons, we have identified a novel gene (named TMPRSS2) that encodes a multimeric protein with a serine p rotease domain. The TMPRSS2 3.8-kb mRNA is expressed strongly in small intestine and weakly in several other tissues. The full-length cDNA e ncodes a predicted protein of 492 amino acids that contains the follow ing domains: (i) A serine protease domain (aa 255-492) of the S1 famil y that probably cleaves at Arg or Lys residues. (ii) An SRCR (scavenge r receptor cysteine-rich) domain (aa 149-242) of group A (6 conserved Cys). This type of domain is involved in the binding to other cell sur face or extracellular molecules. (iii) An LDLRA (LDL receptor class A) domain (aa 113-148). This type of domain forms a binding site for cal cium. (iv) A predicted transmembrane domain (aa 84-106). No typical si gnal peptide was recognized. The gene was mapped to 21q22.3 between ma rkers ERG and D21S56 in the same P1 as MX1. The physiological role of TMPRSS2 and its involve ment in trisomy 21 phenotypes or monogenic dis orders that map to HC21 are unknown. (C) 1997 Academic Press.