Protein S is a vitamin K-dependent plasma glycoprotein synthesized in the liver.
Protein S exists in two forms in the circulation: a free form and a complex form bound to complement protein C4b-binding protein.
Approximately 40% of protein S circulates freely, while 60% is bound to a complementary regulatory protein, C4b binding protein.
Protein S is encoded by the PROS1 gene.
Gene location Chromosome 3.
It is partly homologous to other vitamin K-dependent plasma coagulation proteins, such as protein C and factors VII, IX, and X.
Protein S is a multifunctional enzyme with a critical role in the regulation of coagulation limiting excess clot formation through action on clot initiation and clot propagation.
There are three forms of hereditary protein S deficiency.
It is a cofactor for tissue factor pathway inhibitor, protein S limits clot initiation by inactivating extrinsic factor Xa and as a co-factor for activated protein C, protein S limits clot propagation by inactivating intrinsic factors Va and VIIIa.
With protein S deficiency regulation of coagulation is impaired, and the risk of thrombosis is increased.
Neonatal purpura fulminans s a manifestation of protein S deficiency and is characterized by microvascular thrombosis, and skin necrosis.
It may play a role in the protein functions as either a cofactor for activated protein C (APC) or in binding C4BP.
It functions as a cofactor to Protein C in the inactivation of Factors Va and VIIIa.
Protein S also binds to the nascent complement complex C5,6,7 and prevents this complex from inserting into a membrane, and prevents the inappropriate activation of the complement system, which would cause uncontrolled systemic inflammation.
Mutations in the PROS1 gene can lead to Protein S deficiency which is a rare blood disorder which can lead to an increased risk of thrombosis.
Protein S deficiency may be inherited or acquired.