PROS1 (E7F5H) Rabbit mAb #75390

PROS1 (PROS, Vitamin K-dependent protein S) is a vitamin K-dependent functional protein. It has an N-terminal Gla domain containing multiple Asp carboxylation sites, followed by four EGF repeats, and two C-terminal LG domains. Vitamin K mediates multiple carboxylations of glutamic acid residues in the PROS1 Gla domain. These modifications are required for PROS1 to exert its functions (1).

PROS1 is well known for its anticoagulant role during thrombosis (2,3). The anticoagulation function of PROS1 is exerted by both intrinsic and extrinsic mechanisms. Extrinsically, PROS1 functions as a cofactor in the TFPI (tissue factor pathway inhibitor) to inhibit Factor Xa generation and prevent coagulation (4). Intrinsically, PROS1 functions as a cofactor for activated protein C (aPC) (4). PROS1-aPC promotes degradation of Factors V and VIII, and prevents coagulation and thrombin formation (5). Another important function of PROS1 is as a ligand activator of the TAM (Tyro3, Axl, and MerTK) RTK family receptor. Among the TAM family members, PROS1 binds and activates Tyro3 and MerTK (6-8). The ligand/receptor interactions activate multiple downstream signaling pathways, such as STAT, ERK, Akt, NF-kB, Bcl-2, and FAK (9). PROS1/TAM interactions play important roles in immune and nervous inflammation and homeostasis, cancer development, and immune-related multiple sclerosis (9-11).