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General Comment |
Askew YS, et al 2001 reported that serpinB12 is a novel member of the human OV-serpin family that is widely
expressed and inhibits trypsin-like serine proteinases.
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, the authors 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 as recombinant
SERPINB12 inhibited human trypsin and plasmin, but not thrombin, coagulation factor Xa or
uPA. The second-order rate constants for the inhibitory reactions were 2.5 1.6 x 105 M-1 s-1
and 1.6 0.2 x 104 M-1 s-1, respectively. These data show that SERPINB12 encodes for a new
functional member of the human ov-serpin family.
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