serpin family A member 12, visceral adipose tissue-derived serpin
Vaspin, also called visceral adipose tissue-derived serpin or serpinA12, was identified as an adipokine with insulin-sensitizing effects and has been shown to significantly reduce blood glucose concentrations in various mouse models. As such, vaspin may represent a novel treatment tool for diabetes intervention strategies. Human kallikrein 7 (hK7), which cleaves human insulin within A and B chain, was the first protease target of vaspin inhibited by classical serpin mechanism with high specificity in vitro. This family belongs to the clade A of the serpin superfamily, which includes the classical serine proteinase inhibitors, alpha-1-antitrypsin and alpha-1-antichymotrypsin, protein C inhibitor, kallistatin, and non-inhibitory serpins, like corticosteroid and thyroxin binding globulins. In general, SERine Proteinase INhibitors (serpins) exhibit conformational polymorphism shifting from native to cleaved, latent, delta, or polymorphic forms. Many serpins, such as antitrypsin and antichymotrypsin, function as serine protease inhibitors which regulate blood coagulation cascades. Non-inhibitory serpins perform many diverse functions such as chaperoning proteins or transporting hormones. Serpins are of medical interest because mutants have been associated with blood clotting disorders, emphysema, cirrhosis, and dementia. A classification based on evolutionary relatedness has resulted in the assignment of serpins to 16 clades designated A-P along with some orphans.
Comment:depending on the conformational state, the RC loop is surface accessible in the active form or buried and inserted as the central beta strand in the inactive form.
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