XCE, a new member of the endothelin-converting enzyme and neutral endopeptidase family, is preferentially expressed in the CNS.

In the present study, we have isolated a cDNA encoding a novel member of the family of zinc metallopeptidases that includes neutral endopeptidase and endothelin-converting enzyme. The predicted amino-acid sequence of this enzyme, termed XCE, consists of 775 amino-acids with a single putative membrane-spanning region, an N-terminal cytoplasmic domain of 59 residues, and a large luminal domain that contains a characteristic zinc-binding motif. Western blot analysis of cells stably expressing this new metallopeptidase revealed a glycosylated protein of approximately 95 kDa. XCE mRNA was found to be predominantly expressed in the central nervous system, sympathetic ganglia and in uterine subepithelial cells. In the rat and human CNS, a very specific pattern of neuronal labelling (in presumptive cholinergic interneurons of basal ganglia, basal forebrain neurons, as well as brainstem and spinal cord motoneurons) was detected by in situ hybridization histochemistry. The enzyme substrate, as yet unidentified, might be found among the numerous neuropeptide transmitters which are colocalized with acetylcholine in these neurons.