{PDOC00256}
{PS00284; SERPIN}
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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.
 - 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.

-Consensus pattern: [LIVMFY]-{G}-[LIVMFYAC]-[DNQ]-[RKHQS]-[PST]-F-[LIVMFY]-
                    [LIVMFYC]-x-[LIVMFAH]
-Sequences known to belong to this class detected by the pattern: ALL,  except
 for 7 sequences.
-Other sequence(s) detected in Swiss-Prot: 27.

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

-Last update: December 2004 / Pattern and text revised.

[ 1] Carrell R., Travis J.
     Trends Biochem. Sci. 10:20-24(1985).
[ 2] Carrell R.W., Pemberton P.A., Boswell D.R.
     "The serpins: evolution and adaptation in a family of protease
     inhibitors."
     Cold Spring Harb. Symp. Quant. Biol. 52:527-535(1987).
     PubMed=3502621
[ 3] Huber R., Carrell R.W.
     "Implications of the three-dimensional structure of alpha
     1-antitrypsin for structure and function of serpins."
     Biochemistry 28:8951-8966(1989).
     PubMed=2690952
[ 4] Remold-O'Donneel E.
     FEBS Lett. 315:105-108(1993).
[ 5] Osterwalder T., Contartese J., Stoeckli E.T., Kuhn T.B., Sonderegger P.
     "Neuroserpin, an axonally secreted serine protease inhibitor."
     EMBO J. 15:2944-2953(1996).
     PubMed=8670795
[ 6] Komiyama T., Ray C.A., Pickup D.J., Howard A.D., Thornberry N.A.,
     Peterson E.P., Salvesen G.
     "Inhibition of interleukin-1 beta converting enzyme by the cowpox
     virus serpin CrmA. An example of cross-class inhibition."
     J. Biol. Chem. 269:19331-19337(1994).
     PubMed=8034697
[ 7] Clarke E.P., Sanwal B.D.
     "Cloning of a human collagen-binding protein, and its homology with
     rat gp46, chick hsp47 and mouse J6 proteins."
     Biochim. Biophys. Acta 1129:246-248(1992).
     PubMed=1309665
[ 8] Zou Z., Anisowicz A., Hendrix M.J., Thor A., Neveu M., Sheng S.,
     Rafidi K., Seftor E., Sager R.
     "Maspin, a serpin with tumor-suppressing activity in human mammary
     epithelial cells."
     Science 263:526-529(1994).
     PubMed=8290962
[ 9] Steele F.R., Chader G.J., Johnson L.V., Tombran-Tink J.
     "Pigment epithelium-derived factor: neurotrophic activity and
     identification as a member of the serine protease inhibitor gene
     family."
     Proc. Natl. Acad. Sci. U.S.A. 90:1526-1530(1993).
     PubMed=8434014
[10] Holland L.J., Suksang C., Wall A.A., Roberts L.R., Moser D.R.,
     Bhattacharya A.
     J. Biol. Chem. 267:7053-7059(1992).

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