Structure and sequence of human M/NEI (monocyte/neutrophil elastase inhibitor), an Ov-serpin family gene.

Human monocyte/neutrophil Elastase Inhibitor (M/NEI) is a proteinase inhibitor that regulates the activity of the neutrophil proteases: elastase, cathepsin G and proteinase-3. Evidence indicates that M/NEI belongs to the Ov-serpin family (ovalbumin-related serpins), functionally diverse proteins with shared structural features. Recombinant lambda phage clones were isolated that encompass the full-length M/NEI gene plus upstream and downstream regions. The gene, 9.5kb long, consists of 7 exons and 6 introns. The 5' transcription start site identified by primer extension corresponds to a 60bp exon 1; the translation start site is in exon 2. Southern blots established a gene copy number of one. The 3' untranslated region (UTR) contains three AATAAA/AATTAA sites; these were shown to function as alternative polyadenylation signals. A 14-nucleotide upstream motif including the atypical TATA box TATAAGAG otherwise occurs only twice in GenBank, in the genes encoding neutrophil elastase and proteinase-3, target proteases inhibited by M/NEI. Comparison of M/NEI and previously characterized related genes strongly suggests that all Ov-serpins, despite a difference in chromosomal localization and exon number, nonetheless, share a common basic gene structure. Copyright 1998 Elsevier Science B.V. All rights reserved.