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* Serpins signature *
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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).