CLONING, EXPRESSION, AND CHROMOSOMAL LOCALIZATION OF THE MOUSE MEPRINBETA-SUBUNIT

Meprins are plasma membrane homo- or hetero-oligomeric metalloendopept idases that contain glycosylated alpha and/or beta subunits. This pape r reports the cloning and sequencing of the mouse kidney beta subunit. The primary translation product is composed of 704 amino acids which includes a transient signal sequence of 20 amino acids at the NH2 term inus. The protease domain (Asn-63 to Leu-260) contains the putative zi nc-binding motif characteristic of metalloendopeptidases of the ''asta cin family.'' The COOH terminus contains an epidermal growth factor-li ke domain, a potential membrane-spanning domain, and an additional 26 amino acids. The beta subunit has an overall 42% identity to the alpha subunit, however, a 56-amino acid segment near the COOH terminus of a lpha is missing in beta, and the putative transmembrane and cytoplasmi c domains of the subunits share no significant sequence similarity. NH 2-terminal analyses of detergent-solubilized mature forms revealed tha t, unlike alpha, the prosequence (Leu-21 to Lys-62) is not removed fro m the beta subunit. Northern blot analysis revealed a 2.5-kilobase mes sage for the beta subunit in the kidney and intestine of C57BL/6 and C 3H/He mice. The gene for the beta subunit was localized to mouse chrom osome 18. These studies indicate that alpha and beta probably derived from a common ancestral gene, but have evolved so that their genes are on two different chromosomes, and their tissue-specific expression an d post-translational processing differ.