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.