Antithrombin III (AT3/ATIII) is a non-vitamin K-dependent serine protease that inhibits coagulation by neutralizing the enzymatic activity of thrombin (factors IIa, IXa, Xa). It is the most important anticoagulant molecule in mammalian circulation systems, controlled by its interaction with the cofactor, heparin, which accelerates its interaction with target proteases. This subgroup corresponds to clade C of the serpin superfamily. 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 can cause 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.
Structure:1ATT_A: Bos taurus antithrombin III loop cleaved and inserted
Jiyao W et al.(2023). "The conserved domain database in 2023.",