Protein S (also known asPROS) is avitamin K-dependent plasmaglycoprotein synthesized in theliver. In the circulation, Protein S exists in two forms: a free form and a complex form bound tocomplement proteinC4b-binding protein (C4BP). In humans, protein S is encoded by thePROS1gene.[5][6] Protein S plays a role in coagulation.
Additionally, protein S has a peptide between the Gla domain and the EGF-like domain, that is cleaved bythrombin. The Gla and EGF-like domains stay connected after the cleavage by adisulfide bond. However, protein S loses its function as an APC cofactor following either this cleavage or binding C4BP.[11]
The best characterized function of Protein S is its role in the anticoagulation pathway, where it functions as a cofactor toProtein C in the inactivation ofFactors Va andVIIIa. Only the free form has cofactor activity.[12]
Protein S binds to negatively chargedphospholipids via the carboxylated Gla domain. This property allows Protein S to facilitate the removal of cells that are undergoingapoptosis, a form of structured cell death used by the body to remove unwanted or damaged cells. In healthy cells, an ATP (adenosine triphosphate)-dependent enzyme removes negatively charged phospholipids such as phosphatidyl serine from the outer leaflet of the cell membrane. An apoptotic cell (that is, one undergoingapoptosis) no longer actively manages the distribution of phospholipids in its outer membrane and hence begins to display negatively charged phospholipids on its exterior surface. These negatively charged phospholipids are recognized byphagocytes such asmacrophages. Protein S binds to the negatively charged phospholipids and functions as a bridge between the apoptotic cell and the phagocyte. This bridging expedites phagocytosis and allows the cell to be removed without giving rise toinflammation or other signs of tissue damage.
Protein S does not bind to the nascent complement complex C5,6,7 to prevent it from inserting into a membrane. This is a different complement protein S AKAvitronectin made by the VTN gene, not to be confused with the coagulation protein S made by the PROS gene which this wiki page concerns.
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