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J. Biol. Chem., Vol. 276, Issue 52, 49320-49330, December 28, 2001
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From the 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
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
1 s
1,
respectively. These data show that SERPINB12 encodes for a new functional member of the human ov-serpin family.
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.
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