Background of protein S
Protein S, also known by the gene symbol PROS1, is a vitamin K-dependent plasma protein that was discovered in the late 1970s by ten Cate, Hennis, and Yakovlev. The gene that encodes human Protein S is located on chromosome 3, precisely at the locus 3q11.2. The protein structure consists of a 75-kDa single chain that contains 634 amino acids, which is cleaved into a light chain of 155 amino acids and a heavy chain of 478 amino acids.
As a critical anticoagulant, human Protein S serves as a cofactor to stimulate the activity of Protein C in the degradation of clotting factors Va and VIIIa, thereby reducing the formation of blood clots. It also works antagonistically to FV and FVIII to regulate the coagulation cascade. What’s more is that Protein S has a unique capacity to bind and neutralize the extracellular histones, attributing to its role in the innate immune response.
Protein S-related signaling pathways
Human Protein S-related signaling pathways are intricate and pivotal to the regulation of various cellular functions. The majority of the protein, about 60%, is bound to complement component C4b-binding protein (C4BP) and the balance circulates freely. The binding to C4BP is vital in the complement system and regulating the immune response. Not only does it regulate coagulation, but it also serves as an adaptor molecule to mediate apoptotic cell clearance, and it interacts with tyro-3, Axl, and Mertk (TAM) receptors to limit the inflammatory response and also contributes to phagocytosis.
Protein S related diseases
Over the years, extensive research has revealed that numerous diseases are closely connected with human Protein S, particularly in relation to coagulation abnormalities and autoimmune disorders. Protein S deficiency, either congenital or acquired, can result in recurrent venous thrombosis and pulmonary embolism. In autoimmune diseases such as systemic lupus erythematosus (SLE) and antiphospholipid syndrome (APS), decreased levels of free Protein S are frequently documented. Moreover, emerging evidence has associated abnormal Protein S function with atherosclerosis and sepsis.
From a medical perspective, the function and role of human Protein S in combating diseases are significantly helpful in developing therapeutic strategies. Its unique role as an anticoagulant is paramount in preventing thrombosis and managing cardiovascular diseases. The apoptotic cell clearance function of Protein S also is a potential medicine application, as impaired clearance of apoptotic cells contributes to the pathogenesis of numerous diseases.
List of drug candidates related to Human Protein S
Given the crucial functions and its involvement in various diseases, human Protein S-related drug candidates have started to emerge. These drug candidates mainly aim to enhance the anticoagulant function of Protein S or replace the deficient Protein S in the body. One of these is the recombinant human Protein S, which is currently under pre-clinical studies.
In a nutshell, human Protein S has been recognized for its multifaceted roles, including anticoagulant activities, regulation of inflammation, apoptotic cell clearance, and binding to extracellular histones, making it a crucial player in human homeostasis and disease states. Therefore, further studies to understand the functions and applications of human Protein S, and developing drug candidates targeting this protein, will greatly enhance our ability to combat diseases and benefit human health.