SERPIN

SERine Proteinase INhibitors
SERPIN
SMART accession number:SM00093
Description:
Interpro abstract (IPR023796):

Peptide proteinase inhibitors can be found as single domain proteins or as single or multiple domains within proteins; these are referred to as either simple or compound inhibitors, respectively. In many cases they are synthesised as part of a larger precursor protein, either as a prepropeptide or as an N-terminal domain associated with an inactive peptidase or zymogen. This domain prevents access of the substrate to the active site. Removal of the N-terminal inhibitor domain either by interaction with a second peptidase or by autocatalytic cleavage activates the zymogen. Other inhibitors interact direct with proteinases using a simple noncovalent lock and key mechanism; while yet others use a conformational change-based trapping mechanism that depends on their structural and thermodynamic properties.

Serpins (SERine Proteinase INhibitors) [(PUBMED:14705960), (PUBMED:2690952), (PUBMED:8417965)] belong to MEROPS inhibitor family I4, clan ID. Serpins are proteins that are primarily known as irreversible serine protease inhibitors active against S1 (IPR001254), S8 (IPR000209) and C14 (IPR002398) peptidases. There are both extra- and intra-cellular serpins, which are found in all groups of organisms with the notable exception of fungi [(PUBMED:11116082), (PUBMED:12411597)]. In contrast to "rigid" proteinase inhibitors, such as those of the Kunitz or Kazal families, the serpins are metastable proteins (active-state proteins) which interact with their substrate and irreversibly trap the acyl intermediate as a result of a major conformational change [(PUBMED:11116079)]; they are best described as suicide substrate inhibitors. The common structure of these proteins is a multi-domain fold containing a bundle of 8 or 9 alpha helices and a beta sandwich formed by 3 beta sheets. The reactive centre loop (RCL) is found in the C-terminal part of these proteins.

Serpins and their homologues are a group of high molecular weight (40 to 50 kDa) structurally related proteins involved in a number of fundamental biological processes such as blood coagulation, complement activation, fibrinolysis, angiogenesis, inflammation, tumour suppression and hormone transport. All known serpins have been classified into 16 clades and 10 orphan sequences; the vertebrate serpins can be conveniently classified into six sub-groups [(PUBMED:11116082)]. In human plasma they represent approximately 2% of the total protein, of which 70% is alpha-1-antitrypsin. On the basis of strong sequence similarities, a number of proteins with no known inhibitory activity also belong to this family, these include: angiotensinogen, corticosteroid-binding globulin and thyroxin-binding globulin [(PUBMED:12824063)].

This entry represents the structural domain of serpins. It consists of a cluster of helices and a beta-sandwich.
Family alignment:
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There are 2594 SERPIN domains in 2585 proteins in SMART's nrdb database.

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