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- *********************
- * Serpins signature *
- *********************
-
- 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):
-
- - 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.
- - Human maspin, which seems to function as a tumor supressor [5].
- - A lepidopterian protease inhibitor.
- - Leukocyte elastase inhibitor which, in contrast to other serpins, is an
- intracellular protein.
- - Three 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
- [6].
- - Pigment epithelium-derived factor precursor (PEDF), a protein with a strong
- neutrophic activity [7].
- - Ep45, an estrogen-regulated protein from Xenopus [8].
-
- 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.
-
- -Consensus pattern: [LIVMFY]-x-[LIVMFYAC]-[DNQ]-[RKHQS]-[PST]-F-[LIVMFY]-
- [LIVMFYC]-x-[LIVMFAH]
- -Sequences known to belong to this class detected by the pattern: ALL, except
- for rodent angiotensinogen and vaccinia viruses SPI-3 (K2L).
- -Other sequence(s) detected in SWISS-PROT: 9.
-
- -Note: in position 6 of the pattern, Pro is found in most serpins.
-
- -Last update: June 1994 / Pattern and text revised.
-
- [ 1] Carrell R., Travis J.
- Trends Biochem. Sci. 10:20-24(1985).
- [ 2] Carrell R., Pemberton P.A., Boswell D.R.
- Cold Spring Harbor Symp. Quant. Biol. 52:527-535(1987).
- [ 3] Huber R., Carrell R.W.
- Biochemistry 28:8951-8966(1989).
- [ 4] Remold-O'Donneel E.
- FEBS Lett. 315:105-108(1993).
- [ 5] Zou Z., Anisowicz A., Neveu M., Rafidi K., Sheng S., Sager R.,
- Hendrix M.J., Seftor E., Thor A.
- Science 263:526-529(1994).
- [ 6] Clarke E., Sandwal B.D.
- Biochim. Biophys. Acta 1129:246-248(1992).
- [ 7] Steele F.R., Chader G.J., Johnson L.V., Tombran-Tink J.
- Proc. Natl. Acad. Sci. U.S.A. 90:1526-1530(1993).
- [ 8] Holland L.J., Suksang C., Wall A.A., Roberts L.R., Moser D.R.,
- Bhattacharya A.
- J. Biol. Chem. 267:7053-7059(1992).
-