Protein Z


Protein Z

protein
Name = protein Z
caption =


width =
HGNCid = 9460
Symbol = PROZ
AltSymbols =
EntrezGene = 8858
OMIM = 176895
RefSeq = NM_003891
UniProt = P22891
PDB =
ECnumber =
Chromosome = 13
Arm = q
Band = 34
LocusSupplementaryData =

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.

Physiology

Although it is not enzymatically active, it 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.

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.

Genetics

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 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.

History

Protein Z was first isolated in cattle blood by Prowse and Esnouf in 1977, [Prowse CV, Esnouf MP. "The isolation of a new warfarin-sensitive protein from bovine plasma." Biochem Soc Trans 1977;5:255-256. PMID 892175.] and Broze & Miletich determined it in human plasma in 1984. [Broze GJ Jr, Miletich JP. "Human Protein Z." J Clin Invest 1984;73:933-8. PMID 6707212.]

References

External links

* [http://www.hprd.org/protein/07182 Human Protein Reference Database]


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