SERPINB1 explained

Leukocyte elastase inhibitor (LEI) also known as serpin B1 is a protein that in humans is encoded by the SERPINB1 gene. It is a member of the clade B serpins or ov-serpins (ovalbumin related serpins) founded by ovalbumin.^{[1] [2] [3]}

MNEI (monocyte/neutrophil elastase inhibitor) is the mouse orthologue of human SerpinB1.^[3]

Function

SerpinB1 is a cytoplasmic serine protease inhibitor of polymorphonuclear neutrophils. Among other serine proteases, it specifically inhibits neutrophil elastase, PR3 and cathepsin G, all found in neutrophil granules, by a suicide inhibition mechanism. SerpinB1 was found to reduce tissue damage caused by the mentioned proteases during inflammation and has a role in neutrophil homeostasis in mice. In various infection models (e.g. pneumonia) correlation of SerpinB1 absence and lack of microbial clearance have been shown. Different knockout strains serve as model to investigate the role of SerpinB1 in vivo.^{[4] [5] [6]}

See also

• Serpin

Further reading

• Rasmussen HH, van Damme J, Puype M, etal . Microsequences of 145 proteins recorded in the two-dimensional gel protein database of normal human epidermal keratinocytes. . Electrophoresis . 13 . 12 . 960–9 . 1993 . 1286667 . 10.1002/elps.11501301199 . 41855774 .
• Packard BZ, Lee SS, Remold-O'Donnell E, Komoriya A . A serpin from human tumor cells with direct lymphoid immunomodulatory activity: mitogenic stimulation of human tumor-infiltrating lymphocytes. . Biochim. Biophys. Acta . 1269 . 1 . 41–50 . 1995 . 7578269 . 10.1016/0167-4889(95)00113-7 .
• Sugimori T, Cooley J, Hoidal JR, Remold-O'Donnell E . Inhibitory properties of recombinant human monocyte/neutrophil elastase inhibitor. . Am. J. Respir. Cell Mol. Biol. . 13 . 3 . 314–22 . 1995 . 7654387 . 10.1165/ajrcmb.13.3.7654387.
• Maruyama K, Sugano S . Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides. . Gene . 138 . 1–2 . 171–4 . 1994 . 8125298 . 10.1016/0378-1119(94)90802-8 .
• Evans E, Cooley J, Remold-O'Donnell E . Characterization and chromosomal localization of ELANH2, the gene encoding human monocyte/neutrophil elastase inhibitor. . Genomics . 28 . 2 . 235–40 . 1996 . 8530031 . 10.1006/geno.1995.1136 .
• Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K, etal . Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library. . Gene . 200 . 1–2 . 149–56 . 1997 . 9373149 . 10.1016/S0378-1119(97)00411-3 .
• Zeng W, Silverman GA, Remold-O'Donnell E . Structure and sequence of human M/NEI (monocyte/neutrophil elastase inhibitor), an Ov-serpin family gene. . Gene . 213 . 1–2 . 179–87 . 1998 . 9630619 . 10.1016/S0378-1119(98)00189-9 .
• Sun J, Stephens R, Mirza G, etal . A serpin gene cluster on human chromosome 6p25 contains PI6, PI9 and ELANH2 which have a common structure almost identical to the 18q21 ovalbumin serpin genes. . Cytogenet. Cell Genet. . 82 . 3–4 . 273–7 . 1999 . 9858835 . 10.1159/000015118 . 2024-07-26 . 23659776 .
• Perani P, Zeggai S, Torriglia A, Courtois Y . Mutations on the hinge region of leukocyte elastase inhibitor determine the loss of inhibitory function. . Biochem. Biophys. Res. Commun. . 274 . 3 . 841–4 . 2000 . 10924364 . 10.1006/bbrc.2000.3191 .
• Cooley J, Takayama TK, Shapiro SD, etal . The serpin MNEI inhibits elastase-like and chymotrypsin-like serine proteases through efficient reactions at two active sites. . Biochemistry . 40 . 51 . 15762–70 . 2002 . 11747453 . 10.1021/bi0113925 .
• Korkmaz B, Attucci S, Hazouard E, etal . Discriminating between the activities of human neutrophil elastase and proteinase 3 using serpin-derived fluorogenic substrates. . J. Biol. Chem. . 277 . 42 . 39074–81 . 2002 . 12114510 . 10.1074/jbc.M202918200 . free .
• Benarafa C, Cooley J, Zeng W, etal . Characterization of four murine homologs of the human ov-serpin monocyte neutrophil elastase inhibitor MNEI (SERPINB1). . J. Biol. Chem. . 277 . 44 . 42028–33 . 2003 . 12189154 . 10.1074/jbc.M207080200 . free .
• Strausberg RL, Feingold EA, Grouse LH, etal . Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. . Proc. Natl. Acad. Sci. U.S.A. . 99 . 26 . 16899–903 . 2003 . 12477932 . 10.1073/pnas.242603899 . 139241 . 2002PNAS...9916899M . free .
• Gevaert K, Goethals M, Martens L, etal . Exploring proteomes and analyzing protein processing by mass spectrometric identification of sorted N-terminal peptides. . Nat. Biotechnol. . 21 . 5 . 566–9 . 2004 . 12665801 . 10.1038/nbt810 . 23783563 .
• Mungall AJ, Palmer SA, Sims SK, etal . The DNA sequence and analysis of human chromosome 6. . Nature . 425 . 6960 . 805–11 . 2003 . 14574404 . 10.1038/nature02055 . 2003Natur.425..805M . free .
• Gerhard DS, Wagner L, Feingold EA, etal . The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). . Genome Res. . 14 . 10B . 2121–7 . 2004 . 15489334 . 10.1101/gr.2596504 . 528928 .
• Ahmed M, Forsberg J, Bergsten P . Protein profiling of human pancreatic islets by two-dimensional gel electrophoresis and mass spectrometry. . J. Proteome Res. . 4 . 3 . 931–40 . 2005 . 15952740 . 10.1021/pr050024a .

External links

• The MEROPS online database for peptidases and their inhibitors: I04.006

Notes and References

1. Remold-O'Donnell E, Chin J, Alberts M . Sequence and molecular characterization of human monocyte/neutrophil elastase inhibitor . Proc Natl Acad Sci U S A . 89 . 12 . 5635–9 . Jul 1992 . 1376927 . 49347 . 10.1073/pnas.89.12.5635 . 1992PNAS...89.5635R . free .
2. Web site: Entrez Gene: SERPINB1 serpin peptidase inhibitor, clade B (ovalbumin), member 1.
3. Benarafa C, Remold-O'Donnell E . The ovalbumin serpins revisited: perspective from the chicken genome of clade B serpin evolution in vertebrates . Proc. Natl. Acad. Sci. U.S.A. . 102 . 32 . 11367–72 . August 2005 . 16055559 . 1183561 . 10.1073/pnas.0502934102 . 2005PNAS..10211367B . free .
4. Gong D, Farley K, White M, Hartshorn KL, Benarafa C, Remold-O'Donnell E . Critical role of serpinB1 in regulating inflammatory responses in pulmonary influenza infection . J. Infect. Dis. . 204 . 4 . 592–600 . August 2011 . 21791661 . 10.1093/infdis/jir352 . 3144176.
5. Benarafa C, LeCuyer TE, Baumann M, Stolley JM, Cremona TP, Remold-O'Donnell E . SerpinB1 protects the mature neutrophil reserve in the bone marrow . J. Leukoc. Biol. . 90 . 1 . 21–9 . July 2011 . 21248149 . 10.1189/jlb.0810461 . 3114599.
6. Benarafa C, Priebe GP, Remold-O'Donnell E . The neutrophil serine protease inhibitor serpinb1 preserves lung defense functions in Pseudomonas aeruginosa infection . J. Exp. Med. . 204 . 8 . 1901–9 . August 2007 . 17664292 . 2118684 . 10.1084/jem.20070494 .