Protein Z (PZ) is a vitamin K-dependent, plasma protein that serves as a cofactor for the inhibition of factor Xa by protein Z-dependent protease inhibitor (ZPI) in the presence of calcium ions and phospholipids. ZPI is a member of the serpin superfamily of proteinase inhibitors and inhibits factor Xa in a PZ-dependent fashion, but also inhibits factor XIa in the absence of cofactors.
Protein Z is a gla domain protein and thus vitamin K-dependent, and its functionality is therefore impaired in warfarin therapy. It is a glycoprotein.
Protein Z is not enzymatically active, but is structurally related to several serine proteases of the coagulation cascade (factors VII, IX, X and protein C). The carboxyglutamate residues (which require vitamin K) bind protein Z to phospholipid surfaces.
Protein Z Deficiency
In some studies, deficiency states have been associated with a propensity to thrombosis. Others, however, link it to bleeding tendency.