Protein S, human
Description of Protein S (PS)
Protein S (PS) is a vitamin K-dependent glycoprotein produced in the liver, endothelium and megakaryocytes. The concentration of PS in plasma is ~25 ÃŽÂ¼g/ml (~325 nM) where it acts as a cofactor in the anticoagulant activity of activated Protein C. A deficiency of Protein S (quantitative or qualitative) is a risk factor for vascular thrombosis. Protein S is expressed as a single chain molecule with a molecular weight of 77 kDa. The structure of PS is similar to many other vitamin-K dependent coagulation proteins, consisting of an N-terminal calcium binding domain of 10 ÃŽÂ³-carboxyglutamic acid (gla) residues, followed by a thrombin-sensitive loop region and 4 EGF-like domains. The C-terminal domain does not contain the usual catalytic triad of a proenzyme, but seems instead to be involved in the binding of PS to C4b-binding protein (C4bp). Protein S binds to activated Protein C (APC) in the presence of calcium and negatively charged phospholipid surface to allow APC to proteolytically inactivate coagulation cofactors Va and VIIIa. Enzymatic regulation of PS cofactor activity is through cleavage of PS in the thrombin-sensitive loop region by thrombin or other enzymes, resulting in the loss of calcium binding properties and APC cofactor activity. Another regulatory mechanism is to reduce the availability of PS by the binding of PS to C4bp. In plasma, approximately 60% of Protein S circulates in non-covalent complex with C4bp, making it unavailable for APC cofactor activity. The binding of PS to C4bp may be important in localizing C4bp to damaged cell membranes where it may control activation of complement by the classical pathway1-3.
1. Broze GJ, Miletich JP; Biochemistry and Physiology of Protein C, Protein S and Thrombomodulin; in Hemostasis and Thrombosis, 3rd Edition, eds. RW Colman, J Hirsh, VJ Marder and EW Salzman, pp 259-276, J.B. Lippincott Co., Philadelphia PA, USA, 1994.
2. Comp PC, Doray D, Patton D, Esmon CT; An Abnormal Plasma Distribution of Protein S Occurs in Functional Protein S Deficiency. Blood 67, pp 504-508, 1986.
3. Schwalbe RA, Dahlback B, Nelsestuen GL; Independent Association of Serum Amyloid P Component, Protein S and Complement C4b with C4b-binding Protein and Subsequent Association of the Complex with Membranes; JBC 265, pp 21749-21757, 1990.
GAPS-IG Goat anti-human Protein S, IgG from antiserum
GAPS-AP Goat anti-human Protein S, affinity purified IgG
GAPS-HRP Goat anti-human Protein S, peroxidase labelled IgG
SAPS-IG Sheep anti-human Protein S, IgG from antiserum
SAPS-HRP Sheep anti-human Protein S, peroxidase labelled IgG