PDOC00256 [for PROSITE entry PS00284]
Serpins (SERine Proteinase INhibitors) [
1, 2, 3, 4] are a group of structurally
related proteins. They are high molecular weight (400 to 500 amino acids),
extracellular, irreversible serine protease inhibitors with a well defined
structural-functional characteristic: a reactive region that acts as a 'bait'
for an appropriate serine protease. This region is found in the C-terminal
part of these proteins. Proteins which are known to belong to the serpin
family are listed below (references are only provided for recently determined
α-1 protease inhibitor (α-1-antitrypsin, contrapsin).
Heparin cofactor II.
Complement C1 inhibitor.
Plasminogen activator inhibitors 1 (PAI-1) and 2 (PAI-2).
Glia derived nexin (GDN) (Protease nexin I).
Protein C inhibitor.
Rat hepatocytes SPI-1, SPI-2 and SPI-3 inhibitors.
Human squamous cell carcinoma antigen (SCCA) which may act in the
modulation of the host immune response against tumor cells.
A lepidopteran protease inhibitor.
Leukocyte elastase inhibitor which, in contrast to other serpins, is an
5], a neuronal inhibitor of plasminogen activators and
Cowpox virus crmA [
6], an inhibitor of the thiol protease interleukin-1B
converting enzyme (ICE). CrmA is the only serpin known to inhibit a non-
Some orthopoxviruses probable protease inhibitors, which may be involved in
the regulation of the blood clotting cascade and/or of the complement
cascade in the mammalian host.
On the basis of strong sequence similarities, a number of proteins with no
known inhibitory activity are said to belong to this family:
Birds ovalbumin and the related genes X and Y proteins.
Angiotensinogen; the precursor of the angiotensin active peptide.
Barley protein Z; the major endosperm albumin.
Corticosteroid binding globulin (CBG).
Thyroxine-binding globulin (TBG).
Sheep uterine milk protein (UTMP) and pig uteroferrin-associated protein
Hsp47, an endoplasmic reticulum heat-shock protein that binds strongly to
collagen and could act as a chaperone in the collagen biosynthetic pathway
Maspin, which seems to function as a tumor supressor [
Pigment epithelium-derived factor precursor (PEDF), a protein with a strong
neutrophic activity [
Ep45, an estrogen-regulated protein from Xenopus [
We developed a signature pattern for this family of proteins, centered on a
well conserved Pro-Phe sequence which is found ten to fifteen residues on the
C-terminal side of the reactive bond.
In position 6 of the pattern, Pro is found in most serpins.
December 2004 / Pattern and text revised.
PROSITE method (with tools and information) covered by this documentation:
PS00284; Serpins signature (PATTERN)
1 Authors Carrell R. Travis J.
Source Trends Biochem. Sci. 10:20-24(1985).
2 Authors Carrell R.W. Pemberton P.A. Boswell D.R.
Title The serpins: evolution and adaptation in a family of protease inhibitors.
Source Cold Spring Harb. Symp. Quant. Biol. 52:527-535(1987).
PubMed ID 3502621
3 Authors Huber R. Carrell R.W.
Title Implications of the three-dimensional structure of alpha 1-antitrypsin for structure and function of serpins.
Source Biochemistry 28:8951-8966(1989).
PubMed ID 2690952
4 Authors Remold-O'Donneel E.
Source FEBS Lett. 315:105-108(1993).
5 Authors Osterwalder T. Contartese J. Stoeckli E.T. Kuhn T.B. Sonderegger P.
Title Neuroserpin, an axonally secreted serine protease inhibitor.
Source EMBO J. 15:2944-2953(1996).
PubMed ID 8670795
6 Authors Komiyama T. Ray C.A. Pickup D.J. Howard A.D. Thornberry N.A. Peterson E.P. Salvesen G.
Title Inhibition of interleukin-1 beta converting enzyme by the cowpox virus serpin CrmA. An example of cross-class inhibition.
Source J. Biol. Chem. 269:19331-19337(1994).
PubMed ID 8034697
7 Authors Clarke E.P. Sanwal B.D.
Title Cloning of a human collagen-binding protein, and its homology with rat gp46, chick hsp47 and mouse J6 proteins.
Source Biochim. Biophys. Acta 1129:246-248(1992).
PubMed ID 1309665
8 Authors Zou Z. Anisowicz A. Hendrix M.J. Thor A. Neveu M. Sheng S. Rafidi K. Seftor E. Sager R.
Title Maspin, a serpin with tumor-suppressing activity in human mammary epithelial cells.
Source Science 263:526-529(1994).
PubMed ID 8290962
9 Authors Steele F.R. Chader G.J. Johnson L.V. Tombran-Tink J.
Title Pigment epithelium-derived factor: neurotrophic activity and identification as a member of the serine protease inhibitor gene family.
Source Proc. Natl. Acad. Sci. U.S.A. 90:1526-1530(1993).
PubMed ID 8434014
10 Authors Holland L.J. Suksang C. Wall A.A. Roberts L.R. Moser D.R. Bhattacharya A.
Source J. Biol. Chem. 267:7053-7059(1992).
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