Human N-benzoyl-L-tyrosyl-p-aminobenzoic acid hydrolase (human meprin): genomic structure of the alpha and beta subunits.
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 alpha subunit is approx. 35 kb in size and contains 14 exons. The gene for the beta 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 PPHalpha, which codes for an additional I domain not present in PPHbeta. 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 PPHalpha and PPHbeta are derived from a common ancestor. Sequence analysis of the 5' 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.
Hahn
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Institute of Biochemistry and Molecular Biology and Department of Pediatrics, University of Berne, 3012 Berne, Switzerland. dagmar.hahn@mci.unibe.ch
Illisson
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Metspalu
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Sterchi
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D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D003001:Cloning, Molecular; D019143:Evolution, Molecular; D005091:Exons / Q000235:genetics*; D005786:Gene Expression Regulation / Q000235:genetics; D017930:Genes, Reporter / Q000235:genetics; D006801:Humans; D007438:Introns / Q000235:genetics*; D008666:Metalloendopeptidases / Q000737:chemistry* / Q000235:genetics*; D051379:Mice; D008969:Molecular Sequence Data; D008970:Molecular Weight; D011401:Promoter Regions, Genetic / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis / Q000235:genetics; D020218:Response Elements / Q000235:genetics; D016415:Sequence Alignment; D017384:Sequence Deletion / Q000235:genetics; D014158:Transcription, Genetic / Q000235:genetics
D012333:RNA, Messenger; D008666:Metalloendopeptidases; C053833:meprin A