PS00284

Serpins signature

PROSITE patterns entry
Member databasePROSITE patterns
PROSITE patterns typeconserved site
Short nameSERPIN

Description

Serpins (SERine Proteinase INhibitors)
[7]
[1]
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 sequences): - Alpha-1 protease inhibitor (alpha-1-antitrypsin, contrapsin). - Alpha-1-antichymotrypsin, - Antithrombin III. - Alpha-2-antiplasmin. - 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 intracellular protein. - Neuroserpin
[3]
, a neuronal inhibitor of plasminogen activators and plasmin. - Cowpox virus crmA
[5]
, an inhibitor of the thiol protease interleukin-1B converting enzyme (ICE). CrmA is the only serpin known to inhibit a non- serine proteinase. - 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 (UFAP). - Hsp47, an endoplasmic reticulum heat-shock protein that binds strongly to collagen and could act as a chaperone in the collagen biosynthetic pathway
[4]
. - Maspin, which seems to function as a tumor supressor
[3]
. - Pigment epithelium-derived factor precursor (PEDF), a protein with a strong neutrophic activity
[6]
. - Ep45, an estrogen-regulated protein from Xenopus
[2]
. 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.

References

1.Implications of the three-dimensional structure of alpha 1-antitrypsin for structure and function of serpins. Huber R, Carrell RW. Biochemistry 28, 8951-66, (1989). View articlePMID: 2690952

2.Pigment epithelium-derived factor: neurotrophic activity and identification as a member of the serine protease inhibitor gene family. Steele FR, Chader GJ, Johnson LV, Tombran-Tink J. Proc. Natl. Acad. Sci. U.S.A. 90, 1526-30, (1993). View articlePMID: 8434014

3.Neuroserpin, an axonally secreted serine protease inhibitor. Osterwalder T, Contartese J, Stoeckli ET, Kuhn TB, Sonderegger P. EMBO J. 15, 2944-53, (1996). View articlePMID: 8670795

4.Cloning of a human collagen-binding protein, and its homology with rat gp46, chick hsp47 and mouse J6 proteins. Clarke EP, Sanwal BD. Biochim. Biophys. Acta 1129, 246-8, (1992). View articlePMID: 1309665

5.Inhibition of interleukin-1 beta converting enzyme by the cowpox virus serpin CrmA. An example of cross-class inhibition. Komiyama T, Ray CA, Pickup DJ, Howard AD, Thornberry NA, Peterson EP, Salvesen G. J. Biol. Chem. 269, 19331-7, (1994). View articlePMID: 8034697

6.Maspin, a serpin with tumor-suppressing activity in human mammary epithelial cells. Zou Z, Anisowicz A, Hendrix MJ, Thor A, Neveu M, Sheng S, Rafidi K, Seftor E, Sager R. Science 263, 526-9, (1994). View articlePMID: 8290962

7.The serpins: evolution and adaptation in a family of protease inhibitors. Carrell RW, Pemberton PA, Boswell DR. Cold Spring Harb. Symp. Quant. Biol. 52, 527-35, (1987). PMID: 3502621

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