Characterization of four murine homologs of the human ov-serpin monocyte neutrophil elastase inhibitor MNEI (SERPINB1).
The human ov-serpin monocyte neutrophil elastase inhibitor (MNEI) is encoded by a single gene SERPINB1. It is a highly efficient inhibitor of neutrophil granule proteases. Four murine genes with high sequence identity with MNEI were identified and fully sequenced, and these were named EIA, EIB, EIC, and EID. EIA, EIB and EIC showed the same seven-exon gene structure as SERPINB1. However, EIC included an additional, alternatively spliced, exon due to the insertion of an endogenous retrovirus-like sequence. EID lacked several exons and is a pseudogene. Reverse transcriptase-PCR showed that EIA, like MNEI, is expressed at high levels in many tissues. EIB is mainly expressed in brain, and EIC was only expressed as splicing variants unlikely to encode a functional serpin. Upon incubation with serine proteases, EIA formed inhibitory covalent complexes with pancreatic and neutrophil elastases, cathepsin G, proteinase-3, and chymotrypsin, as previously shown for MNEI, whereas EIB was only able to do so with cathepsin G. According to the new serpin nomenclature, the genes encoding EIA, EIB, EIC, and EID will be called Serpinb1, Serpinb1b, Serpinb1c, and Serpinb1-ps1. These data demonstrate that the four murine homologs of MNEI have met different evolutionary fates, and that EIA is the mouse ortholog of MNEI.
Center for Blood Research, Boston, Massachusetts 02115, USA. benarafa@cbr.med.harvard.edu
Charaf
C
Benarafa
Jessica
J
Cooley
Weilan
W
Zeng
Phillip I
PI
Bird
Eileen
E
Remold-O'Donnell
D000595:Amino Acid Sequence; D000818:Animals; D005075:Biological Evolution; D056649:Cathepsin G; D002403:Cathepsins / Q000737:chemistry; D040342:Genetic Structures; D006801:Humans; D019272:Leukocyte Elastase / Q000737:chemistry; D051379:Mice; D008969:Molecular Sequence Data; D012333:RNA, Messenger / Q000032:analysis; D012697:Serine Endopeptidases; D015843:Serpins / Q000737:chemistry / Q000235:genetics*
D012333:RNA, Messenger; D015843:Serpins; D002403:Cathepsins; D012697:Serine Endopeptidases; C534094:CTSG protein, human; D056649:Cathepsin G; C534096:Ctsg protein, mouse; D019272:Leukocyte Elastase