What Is Protein S?

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  • Written By: Sandi Johnson
  • Edited By: John Allen
  • Last Modified Date: 07 September 2019
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Protein S is an anticoagulant protein in the human body that is strongly linked with similar vitamin K-dependent proteins such as protein C. In fact, protein S in its free form works in conjunction with protein C to actively prevent blood clots. A second form of the protein, known as the complex form, is bonded with a protein known as C4b. Combined, C4b and the complex form of S cleave to damaged cells after injuries to clean internal tissues without causing further damage.

In terms of protein types, protein S is a glycoprotein. Viewing molecular construction diagrams and microscopic slides, researchers have observed polypeptide side-chains attaching to glycans to create glycoproteins. This class of proteins assists with interactions between cells in virtually innumerable capacities. Such proteins serve purposes in the human body from binding cells or tissue fibers to adhering platelets to blood vessel linings, as well as molecular activity associated with blood clotting and damaged cell removal. Scientists in Seattle, Washington first identified the PROS1 gene and, specifically, protein S in the late 1970s, drawing on the city's initial to name the new protein discovery.


The primary responsibility of this free form glycoprotein is to bond with specific cells to inhibit clotting within the bloodstream. Unless bound to C4b, protein S circulates freely within the body, with increases in blood levels triggered by injuries, disease, or the presence of foreign invaders that affect blood viscosity. When an injury occurs, both the free and complex forms activate. Free form prevents clotting to keep blood flowing unimpeded while the complex form bonded to C4b carries away damaged cells.

Endothelium cells, the cells that make up the inner lining of blood vessels, secrete protein S, making it available throughout the circulatory system. Both forms of protein S, free form and complex alike, are found in the bloodstream, whether or not injuries or infections are present. Properly regulated levels of protein S and similar anticoagulants allow for normal clotting necessary to prevent blood loss in the event of an injury but inhibit clotting within veins to mitigate the risk associated with embolus. An embolus is a dangerous blood clot that forms within a vein, then breaks loose to travel through the circulatory system, risking blockages, strokes, and other complications.

Certain forms of thrombosis, the formation of a blood clot within a vein which blocks blood flow, are caused by a protein S deficiency. Deficiency may be inherited at birth or result from vitamin K deficiency or hepatic diseases. Although a rare disorder, blood tests can determine if a patient suffers from such a deficiency.


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