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