CPB2

CPB2, or carboxypeptidase B2, is a human gene that encodes an enzyme also known as thrombin-activatable fibrinolysis inhibitor (TAFI). The enzyme is secreted as an inactive zymogen, procarboxypeptidase B2, into the blood plasma, where it becomes activated by the thrombin-thrombomodulin complex on endothelial surfaces. CPB2 belongs to the family of zinc-dependent metallocarboxypeptidases; its catalytic activity requires a zinc ion at the active site.

Functionally, active CPB2 removes C-terminal lysine and arginine residues from partially degraded fibrin and other peptides. This de-lysination reduces the affinity of plasminogen for fibrin, decreasing plasmin generation and thereby inhibiting fibrinolysis. In this way, CPB2/TAFI modulates clot stability and links coagulation with the fibrinolytic system.

Structure and localization: CPB2 is secreted into the plasma and circulates as a glycosylated protein. Its activity depends on proper zinc coordination and proteolytic activation by thrombin-thrombomodulin.

Clinical significance: Variations in CPB2 activity or levels of TAFI have been studied as potential modifiers of thrombotic and bleeding risk. Some studies associate higher CPB2/TAFI activity with reduced fibrinolysis and an increased risk of venous thromboembolism or stroke, while lower activity can be linked to bleeding tendencies. Genetic variants in CPB2 have been investigated for associations with thrombosis and inflammatory conditions, but findings are not yet consistent enough for routine clinical use. CPB2/TAFI measurements are primarily used in research contexts as markers of fibrinolytic potential.