TY - JOUR
T1 - Structure and sequence of human M/NEI (monocyte/neutrophil elastase inhibitor), an Ov-serpin family gene
AU - Zeng, Weilan
AU - Silverman, Gary A.
AU - Remold-O'Donnell, Eileen
N1 - Funding Information:
We thank Allison Bartuski for guidance in phage library screening, Jessica Cooley for developing the PCR assay for custom screening the P1 library, and Dr Philip Auron (Harvard Institute of Medicine) for advice and valuable discussions. This work was supported by National Institutes of Health grants HL41579 (E.RO'D) and CA69331 (G.A.S) and grant P972 (E.RO'D) from the Cystic Fibrosis Foundation.
PY - 1998/6/15
Y1 - 1998/6/15
N2 - 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, 9.5 kb long, consists of 7 exons and 6 introns. The 5' transcription start site identified by primer extension corresponds to a 60 bp 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/ATTAAA 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.
AB - 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, 9.5 kb long, consists of 7 exons and 6 introns. The 5' transcription start site identified by primer extension corresponds to a 60 bp 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/ATTAAA 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.
KW - Elastase inhibitor
KW - Gene structure
KW - Protease inhibitor
KW - Serpins
UR - https://www.scopus.com/pages/publications/0032526189
U2 - 10.1016/S0378-1119(98)00189-9
DO - 10.1016/S0378-1119(98)00189-9
M3 - Article
C2 - 9630619
AN - SCOPUS:0032526189
SN - 0378-1119
VL - 213
SP - 179
EP - 187
JO - Gene
JF - Gene
IS - 1-2
ER -