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Originally published In Press as doi:10.1074/jbc.M108879200 on October 16, 2001

J. Biol. Chem., Vol. 276, Issue 52, 49320-49330, December 28, 2001
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SERPINB12 Is a Novel Member of the Human ov-serpin Family That Is Widely Expressed and Inhibits Trypsin-like Serine Proteinases*

Yuko S. AskewDagger , Stephen C. PakDagger , Cliff J. LukeDagger , David J. AskewDagger , Sule CataltepeDagger , David R. MillsDagger , Hiroshi Kato§, Jessica Lehoczky, Ken Dewar, Bruce Birren, and Gary A. SilvermanDagger ||

From the Dagger  Department of Pediatrics, Harvard Medical School, Children's Hospital, Boston, Massachusetts 02115, the § Department of Obstetrics and Gynecology, Yamaguchi University School of Medicine, 1-1-1 Minami-Kogushi, Ube, Yamaguchi 755-8505, Japan, and the  Whitehead Institute for Biomedical Research/MIT Center for Genome Research, Cambridge, Massachusetts 02141

Members of the human serpin family regulate a diverse array of serine and cysteine proteinases associated with essential biological processes such as fibrinolysis, coagulation, inflammation, cell mobility, cellular differentiation, and apoptosis. Most serpins are secreted and attain physiologic concentrations in the blood and extracellular fluids. However, a subset of the serpin superfamily, the ov-serpins, also resides intracellularly. Using high throughput genomic sequence, we identified a novel member of the human ov-serpin gene family, SERPINB12. The gene mapped to the ov-serpin cluster at 18q21 and resided between SERPINB5 (maspin) and SERPINB13 (headpin). The presence of SERPINB12 in silico was confirmed by cDNA cloning. Expression studies showed that SERPINB12 was expressed in many tissues, including brain, bone marrow, lymph node, heart, lung, liver, pancreas, testis, ovary, and intestines. Based on the presence of Arg and Ser at the reactive center of the RSL, SERPINB12 appeared to be an inhibitor of trypsin-like serine proteinases. This hypothesis was confirmed because recombinant SERPINB12 inhibited human trypsin and plasmin but not thrombin, coagulation factor Xa, or urokinase-type plasminogen activator. The second-order rate constants for the inhibitory reactions were 2.5 ± 1.6 × 105 and 1.6 ± 0.2 × 104 M-1 s-1, respectively. These data show that SERPINB12 encodes for a new functional member of the human ov-serpin family.


* This work was supported by Grants CA87006 and CA86002 from the NCI, National Institutes of Health (NIH) and by Grants HD07466, HD28475, and HD18655 from the NICHD, NIH.The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

The nucleotide sequence(s) reported in this paper has been submitted to the GenBankTM/EMBL Data Bank with accession number(s) AF411191.

|| To whom correspondence should be addressed: Children's Hospital, 300 Longwood Ave., Enders 970, Boston, MA 02115-5737. Tel.: 617-355-6416; Fax: 617-355-7677; E-mail: gary.silverman@tch.harvard.edu.


Copyright © 2001 by The American Society for Biochemistry and Molecular Biology, Inc.
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Copyright © 2001 by the American Society for Biochemistry and Molecular Biology.