RGD Reference Report - Protein Z, an anticoagulant protein with expanding role in reproductive biology. - Rat Genome Database

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Protein Z, an anticoagulant protein with expanding role in reproductive biology.

Authors: Almawi, WY  Al-Shaikh, FS  Melemedjian, OK  Almawi, AW 
Citation: Almawi WY, etal., Reproduction. 2013 Jun 27;146(2):R73-80. doi: 10.1530/REP-13-0072. Print 2013 Aug.
RGD ID: 11352284
Pubmed: PMID:23690629   (View Abstract at PubMed)
DOI: DOI:10.1530/REP-13-0072   (Journal Full-text)

Protein Z (PZ) is a vitamin K-dependent factor characterized by its homology to other vitamin K-dependent factors (factors VII, IX, and X, protein C and protein S), but lacks any enzymatic activity. Instead, PZ acts as a cofactor for the inhibition of factor Xa through the serpin PZ-dependent protease inhibitor (ZPI). PZ deficiency is associated with a procoagulant state, highlighted by excessive FXa secretion and thrombin production, and is linked with several thrombotic disorders, including arterial vascular and venous thromboembolic diseases. A role for the PZ-ZPI complex in the regulation of physiological pregnancy has been demonstrated, highlighted by the progressive elevation in PZ levels in the first trimester of gestation, which then steadily decline toward delivery. An association between altered plasma PZ concentrations and adverse pregnancy outcomes (recurrent miscarriage, stillbirth, preeclampsia, intrauterine growth restriction, and placental abruption) has been reported. The mechanism by which PZ deficiency leads to adverse pregnancy outcomes is not clear, but it is multifactorial. It may be attributed to the anti-PZ IgG and IgM autoantibodies, which apparently act independently of classical antiphospholipid antibodies (lupus anticoagulant, anticardiolipin, and anti-beta2-glycoprotein I antibodies). PZ deficiency has also been reported to be constitutional, and a number of variants in the PROZ (PZ) gene and SERPINA10 (ZPI) gene are linked with specific adverse pregnancy complications. This review summarizes the relationship between adverse pregnancy outcomes and acquired and constitutional PZ-ZPI deficiency, in order to understand whether or not PZ deficiency could be considered as a risk factor for poor pregnancy outcomes.

Molecular Pathway Annotations    Click to see Annotation Detail View

RGD Manual Annotations

Objects Annotated

Genes (Rattus norvegicus)
Proz  (protein Z, vitamin K-dependent plasma glycoprotein)
Serpina10  (serpin family A member 10)

Genes (Mus musculus)
Proz  (protein Z, vitamin K-dependent plasma glycoprotein)
Serpina10  (serine (or cysteine) peptidase inhibitor, clade A (alpha-1 antiproteinase, antitrypsin), member 10)

Genes (Homo sapiens)
PROZ  (protein Z, vitamin K dependent plasma glycoprotein)
SERPINA10  (serpin family A member 10)


Additional Information