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PROSITE documentation PDOC00256 [for PROSITE entry PS00284]

Serpins signature





Description

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 sequences):

  • α-1 protease inhibitor (α-1-antitrypsin, contrapsin).
  • α-1-antichymotrypsin,
  • Antithrombin III.
  • α-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 [5], a neuronal inhibitor of plasminogen activators and plasmin.
  • 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- 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 [7].
  • Maspin, which seems to function as a tumor supressor [5].
  • Pigment epithelium-derived factor precursor (PEDF), a protein with a strong neutrophic activity [8].
  • Ep45, an estrogen-regulated protein from Xenopus [9].

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.

Note:

In position 6 of the pattern, Pro is found in most serpins.

Last update:

December 2004 / Pattern and text revised.

Technical section

PROSITE method (with tools and information) covered by this documentation:

SERPIN, PS00284; Serpins signature  (PATTERN)


References

1AuthorsCarrell R. Travis J.
SourceTrends Biochem. Sci. 10:20-24(1985).

2AuthorsCarrell R.W. Pemberton P.A. Boswell D.R.
TitleThe serpins: evolution and adaptation in a family of protease inhibitors.
SourceCold Spring Harb. Symp. Quant. Biol. 52:527-535(1987).
PubMed ID3502621

3AuthorsHuber R. Carrell R.W.
TitleImplications of the three-dimensional structure of alpha 1-antitrypsin for structure and function of serpins.
SourceBiochemistry 28:8951-8966(1989).
PubMed ID2690952

4AuthorsRemold-O'Donneel E.
SourceFEBS Lett. 315:105-108(1993).

5AuthorsOsterwalder T. Contartese J. Stoeckli E.T. Kuhn T.B. Sonderegger P.
TitleNeuroserpin, an axonally secreted serine protease inhibitor.
SourceEMBO J. 15:2944-2953(1996).
PubMed ID8670795

6AuthorsKomiyama T. Ray C.A. Pickup D.J. Howard A.D. Thornberry N.A. Peterson E.P. Salvesen G.
TitleInhibition of interleukin-1 beta converting enzyme by the cowpox virus serpin CrmA. An example of cross-class inhibition.
SourceJ. Biol. Chem. 269:19331-19337(1994).
PubMed ID8034697

7AuthorsClarke E.P. Sanwal B.D.
TitleCloning of a human collagen-binding protein, and its homology with rat gp46, chick hsp47 and mouse J6 proteins.
SourceBiochim. Biophys. Acta 1129:246-248(1992).
PubMed ID1309665

8AuthorsZou Z. Anisowicz A. Hendrix M.J. Thor A. Neveu M. Sheng S. Rafidi K. Seftor E. Sager R.
TitleMaspin, a serpin with tumor-suppressing activity in human mammary epithelial cells.
SourceScience 263:526-529(1994).
PubMed ID8290962

9AuthorsSteele F.R. Chader G.J. Johnson L.V. Tombran-Tink J.
TitlePigment epithelium-derived factor: neurotrophic activity and identification as a member of the serine protease inhibitor gene family.
SourceProc. Natl. Acad. Sci. U.S.A. 90:1526-1530(1993).
PubMed ID8434014

10AuthorsHolland L.J. Suksang C. Wall A.A. Roberts L.R. Moser D.R. Bhattacharya A.
SourceJ. Biol. Chem. 267:7053-7059(1992).



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