Abstract
Protein S is a vitamin K–dependent plasma glycoprotein circulating in plasma at a
concentration of around 350 nM. Approximately 60% of protein S in human plasma is
bound to the complement regulatory protein C4b-binding protein (C4BP) in a high-affinity,
high-molecular-weight complex. Protein S in plasma has multiple anticoagulant properties
and heterozygous protein S deficiency is associated with increased risk of venous
thrombosis. Homozygous deficiency in man and mice is associated with severe thrombosis
in fetal life, defects in the vascular system development, and not compatible with
life. Protein S has additional functions beyond being an anticoagulant. It affects
the complement regulatory properties of C4BP, and moreover, protein S interacts with
tyrosine kinase receptors of the TAM family, which comprises Tyro3, Axl, and Mer.
The TAM receptor interaction is important for the ability of protein S to stimulate
phagocytosis of apoptotic cells. This review will discuss the multiple functions of
protein S, describing its role as cofactor to activated protein C with a subsequent
focus on the other functions of protein S.
Keywords
Gas6 - Axl - Tyro3 - Mer - C4b-binding protein - C4BP - protein C - blood coagulation
