Protein S

Protein S (also known as S-Protein) is a is_associated_with::vitamin K-dependent plasma is_associated_with::glycoprotein synthesized in the endothelium. In the circulation, Protein S exists in two forms: a free form and a complex form bound to complement protein is_associated_with::C4b-binding protein (C4BP). In humans, protein S is encoded by the PROS1 is_associated_with::gene.

Function
The best characterized function of Protein S is its role in the anti is_associated_with::coagulation pathway, where it functions as a cofactor to is_associated_with::Protein C in the inactivation of Factors Va and VIIIa. Only the free form has cofactor activity.

Protein S can bind to negatively charged is_associated_with::phospholipids via the carboxylated GLA domain. This property allows Protein S to function in the removal of cells which are undergoing is_associated_with::apoptosis. is_associated_with::Apoptosis is a form of cell death that is used by the body to remove unwanted or damaged cells from tissues. Cells, which are apoptotic (i.e. in the process of is_associated_with::apoptosis), no longer actively manage the distribution of phospholipids in their outer membrane and hence begin to display negatively charged phospholipids, such as phosphatidyl serine, on the cell surface. In healthy cells, an ATP (is_associated_with::Adenosine triphosphate)-dependent enzyme removes these from the outer leaflet of the cell membrane. These negatively charged phospholipids are recognized by is_associated_with::phagocytes such as is_associated_with::macrophages. Protein S can bind to the negatively charged phospholipids and function as a bridging molecule between the apoptotic cell and the phagocyte. The bridging property of Protein S enhances the phagocytosis of the apoptotic cell, allowing it to be removed 'cleanly' without any symptoms of tissue damage such as is_associated_with::inflammation occurring.

Protein S also binds to the nascent complement complex C5,6,7 and prevents this complex from inserting into a membrane. This function prevents the inappropriate activation of the complement system, which would cause uncontrolled systemic inflammation. In fact, Protein S was first discovered in 1977 in this role and it is named after the membrane site that it occupies in the complex.

Pathology
Mutations in the PROS1 gene can lead to is_associated_with::Protein S deficiency which is a rare blood disorder which can lead to an increased risk of is_associated_with::thrombosis.

Interactions
Protein S has been shown to interact with is_associated_with::Factor V.