ABSTRACT
Background Human thrombin-activatable brinolysis inhibitor (TAFI) (EC 3.4.17.20; UniProt, Q96IY4), also known as plasma pro-carboxypeptidase B, R, and U, is a plasma metallocarboxypeptidase that attenuates brinolysis [1-10]. TAFI circulates in plasma as a 58 kDa protein with signicant intrinsic activity [11,12]. e majority of the sites that undergo transglutaminase-mediated cross-linking to brin are primarily located on the heavily glycosylated pro-peptide, suggesting that TAFI becomes incorporated into the brin clot during later stages of the coagulation cascade [13]. A variety of trypsin-like proteinases have been shown to remove this peptide, generating the mature protein, TAFIa [4,14-17]. e isoelectric point (pI) of this proteolytically cleaved protein is around pH 8.5, which is signicantly more basic than that of TAFI (pI 5.5) [18]. TAFIa remains in circulation by forming complexes with α2-macroglobulin and pregnancy zone protein [19] but is highly unstable, a feature initially attributed to proteolytic cleavage. However, this instability is now thought to result from a temperature-dependent conformational change that occurs within minutes of activation [4,20-22].
