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, 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 x 10(5) and 1.6 +/- 0.2 x 10(4) M(-1) S(-1), respectively. These data show that SERPINB12 encodes for a new functional member of the human ov-serpin family.
Askew
Y S
YS
Department of Pediatrics, Harvard Medical School, Children's Hospital, Boston, Massachusetts 02115, USA.
Pak
S C
SC
Luke
C J
CJ
Askew
D J
DJ
Cataltepe
S
S
Mills
D R
DR
Kato
H
H
Lehoczky
J
J
Dewar
K
K
Birren
B
B
Silverman
G A
GA
D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D003001:Cloning, Molecular; D006801:Humans; D008969:Molecular Sequence Data; D005810:Multigene Family; D011489:Protein Denaturation; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D016415:Sequence Alignment; D015842:Serine Proteinase Inhibitors / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D015843:Serpins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D014018:Tissue Distribution
D011993:Recombinant Fusion Proteins; C445320:SERPINB12 protein, human; D015842:Serine Proteinase Inhibitors; D015843:Serpins