Protein Z is a member of the coagulation cascade, the group of blood proteins that leads to the formation of blood clots. It is vitamin K-dependent, and its functionality is therefore impaired in warfarin therapy. It is a glycoprotein.
Although it is not enzymatically active, it is structurally related to several serine proteases of the coagulation cascade: factors VII, IX and X. The carboxyglutamate residues (which require vitamin K) bind protein Z to phospholipid surfaces.
The main role of protein Z appears to be the degradation of factor Xa. This is done by protein Z-related protease inhibitor (ZPI), but the reaction is accelerated 1000-fold by the presence of protein Z. Oddly, ZPI also degrades factor XI, but this reaction does not require the presence of protein Z.
In some studies, deficiency states have been associated with a propensity to thrombosis. Others, however, link it to bleeding tendency; there is no clear explanation for this, as it acts physiologically as an inhibitor, and deficiency would logically have led to a predisposition for thrombosis.
It is 62 kDa large and 396 amino acids long. The PROZ gene has been linked to the thirteenth chromosome (13q34).
It has four domains: a gla-rich (carboxyglutamate) region, two EGF-like domains and a trypsin-like domain. It lacks the serine residue that would make it catalytically active as a serine protease.
protein Z was first isolated in cattle blood by Prowse and Esnouf in 1977, and Broze & Miletich determined it in human plasma in 1984.
Protein Z-dependent protease inhibitor (aka ZPI) is a protein circulating in the blood which inhibits factors Xa and XIa of the coagulation cascade. It is a member of the class of the serine protease inhibitors (serpins). Its name implies that it requires protein Z, another circulating protein, to function properly, but this only applies to its inhibition of factor X.
It is about 72 kDa heavy and 444 amino acids large. It is produced by the liver.
The gene for ZPI is probably located on the 14th chromosome.
Water et al found deficiency of ZPI in 4.4% of a cohort of patients with thrombophilia (a tendency to thrombosis).
Han et al first described ZPI in 1998. The same group further characterised it in 2000.
DiaPharma Anti-Protein Z is an ELISA designed with highly purified human protein Z, obtained with non-denaturing methods, for the measurement of IgM or IgG isotype autoantibodies targeted to protein Z.
Sources: DiaPharma, Wikipedia, PubMed