Prothrombotic phenotype of protein Z deficiency

Protein Z (PZ) is a vitamin K-dependent plasma protein whose function has b een uncertain. The structure of PZ is very similar to that of the coagulati on-related factors VII, IX, and X and PC. but PZ differs from these other p roteins in that it is not the zymogen of a serine protease. We have shown r ecently that PZ forms a calcium ion-dependent complex with activated factor X at phospholipid surfaces and that this interaction leads to the inhibiti on of activated factor X activity through, in part, the action of a previou sly unidentified plasma protein named PZ-dependent protease inhibitor. Here in. we report that the presence of PZ dampens the coagulation response in h uman plasma and that concomitant PZ deficiency dramatically increases the s everity of the prothrombotic phenotype of factor V-Leiden mice. The results indicate that PZ plays a physiologically important role in the regulation of coagulation.