N-Benzoyl-L-tyrosyl-p-aminobenzoic acid hydrolase (PPH, human meprin), a zinc-metalloendopeptidase of the astacin family, consists of two similar subunits. As well as in small-intestinal epithelial cells, the enzyme is found in lamina propria leucocytes, human cancer cells and colorectal cancer tissue, making it a potential candidate for a role in tumour formation and cancer progression. To elucidate the mechanisms that control PPH gene expression and to gain more insights into the evolutionary relationship of the two subunits, we analysed the complete exon-intron organization and searched for putative regulatory elements in 3 kb of the upstream region of both genes. The human gene for the α subunit is approx. 35 kb in size and contains 14 exons. The gene for the β subunit is organized in 15 exons and spans approx. 27 kb. A comparison of both genes indicates strong structural similarities. The exons are almost identical in size, except exon 13 in PPHα, which codes for an additional I domain not present in PPHβ. The locations of the respective exon-intron junctions and the intron phases are almost identical; five of them contain conserved split codons. The main variation is in the intron lengths. It can be concluded that PPHα and PPHβ are derived from a common ancestor. Sequence analysis of the 5ʹ flanking DNA with a computer search for promoter elements and different promoter constructs transfected into Caco-2 cells revealed a number of potential regulatory motifs and suggests that each of the two genes is regulated independently.

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Author notes

The nucleotide sequence data reported in this paper will appear in DDBJ, EMBL and GenBank Nucleotide Sequence Databases under the accession numbers AJ251058 for PPHα and AJ251059 for PPHβ.