rmProtein S, CF (50 UG)

Background: Protein S/PROS1

Anticoagulant Protein S (PROS1) is a 71 kDa plasma vitamin K-dependent glycoprotein characterized by the presence of the post-translational modification of specific glutamic acid residues to gamma-carboxyglutamic acid (Gla) in the N-terminal region. In addition to the N-terminal Gla domain, mature PROS1 contains a thrombin‑sensitive thumb loop, four tandem EGF-like domains and a C-terminal sex hormone-binding globulin (SHBG) domain composed of two Laminin G (LG) domains (1). Mouse PROS1 shares 80% aa sequence identity with human PROS1. Hundreds of mutations in humans have been reported throughout all the domains of the protein, typically resulting in PROS1 deficiency and an increase in the risk of thrombophilia (2, 3). PROS1 is expressed in many cell types supporting its reported involvement in multiple biological processes that include coagulation, apoptosis, cancer development and progression, and the innate immune response (4-9). PROS1 exists in plasma both in complex with C4b-binding protein (C4BP) (60%) and in a free form (40%). Both forms of PROS1 have anticoagulant activity either directly through inhibition of Factor X systems and prothrombinase while in complex with C4BP (5, 10) or in its well-established role as a cofactor of activated protein C (APC) inactivation of procoagulants FVa and FVIIIa (4). The free form of PROS-1 is also a ligand for a subfamily of receptor tyrosine kinases known as TAMs, which is composed of TYRO3, AXL, and MERTK (11). PROS-1 binds these tyrosine kinase receptors through its LG domains to activate downstream signaling pathways involved in tumor development and progression (7, 8, 11, 12).