Cloning and structural analysis of leydin, a novel human serine protease expressed by the Leydig cells of the testis

We present the cloning and structural analysis of a novel member of the lar ge family of trypsin-related serine proteases. Northern blot analysis shows that this protease, in adult tissues, is expressed almost exclusively in t he human testis. In addition, a larger transcript was detected in relativel y high abundance in several embryonic tissues, indicating different functio ns during embryonic and adult life. Sera raised against this protease was u sed to locate the expression in adult tissues to the testosterone producing cells of the testis, the interstitial Leydig cells. We therefore propose t he name leydin for this novel protease. Leydin is clearly distinct from acr osin, the other testis-specific serine protease which is expressed by the s permatocytes. Leydin is probably a two-chain protease such as acrosin, pros tasin, and coagulation factor XI. The heavy chain consists of 246 amino aci ds, corresponding to a molecular mass of 27384 Da and a net charge of +10.7 6. The size of the light chain is between 9 and 18 amino acids depending on the site of proteolytic cleavage, which remains to be determined. The amin o-acid residues surrounding the active site indicate a trypsin-like cleavag e specificity. The presence of two dibasic sequences Arg-Arg and Lys-Arg at the N-terminus of the heavy chain indicate that one or more subtilisin-lik e endopeptidases are responsible for the processing of leydin. However, ley din may also be activated by a trypsin-like enzyme, possibly by auto cataly sis.