Domain Structure of Protein S
The domain structure of protein S is represented, where: GLA = region containing γ-carboxyglutamic acid residues, EGF = region containing sequences homologous to human epidermal growth factor, TSR = thrombin sensitive region, ? = region of unknown function which replaces the catalytic triad found in vitamin K-dependent serine proteases.
Price $176.00/100 µg ($159.00/min. 5)
Size 100 µg Formulation 50% glycerol/water (v/v) Storage -20°C Purity >95% by SDS-PAGE Activity Determination N/A Shelf Life (properly stored) 12 months
Protein S is a single chain vitamin K-dependent protein which is thought to function in both the coagulation and complement cascades (1,2). Approximately 60% of protein S circulating in plasma is complexed to C4b binding protein (C4BP). It has been suggested that g-carboxyglutamic acid (gla) dependent binding of protein S to negatively charged phospholipids may function to concentrate C4BP at cell surfaces following injury.
In the coagulation system, protein S functions as an anticoagulant cofactor protein. Activated protein C (APC) forms a 1:1 stoichiometric complex with protein S in the presence of Ca2+ and phospholipid vesicles (Kd=6x10-9M) (3). In the presence of protein S, a moderate increase (3-10 fold) in the rate of factor Va and factor VIIIa inactivation by APC is observed in plasma and on the surface of unstimulated platelets. Protein S bound to C4BP does not possess APC cofactor activity. Recently, an additional binding protein which enhances the activity of protein S has been described (4). Proteolytic inactivation of protein S by thrombin has been proposed as a regulatory mechanism in this system. A single cleavage by thrombin abolishes protein S cofactor activity by removing an NH2-terminal peptide (Mr=8000) which contains the gla domain.
The domain structure of protein S is similar to that of the other vitamin K-dependant coagulation factors with the exception that protein S does not possess the catalytic triad. Protein S is a single chain protein containing 10 gla residues in the NH2-terminal domain and 4 epidermal growth factor (EGF) domains.
Human protein S is isolated from fresh frozen plasma by a combination of conventional methods (9) and immunoaffinity chromatography as described by Jenny et al. (5). Purified protein S is supplied in 50% (vol/vol) glycerol/H2O and should be stored at -20°C. Purity is determined by SDS-PAGE analysis.
|Load||Human Protein S, 1 µg per lane|
|Standard||SeeBluePlus 2; Myosin (191 kDa), Phosphorylase B (97 kDa), BSA (64 kDa), Glutamic Dehydrogenase (51 kDa), Alcohol Dehydrogenase (39 kDa), Carbonic Anhydrase (28 kDa), Myoglobin Red (19 kDa), Lysozyme (14 kDa)|
|Localization||Plasma, free and complexed to C4BP|
|Plasma concentration||10 µg/ml (free) (6)|
|Mode of action||Cofactor for activated protein C|
|Molecular weight||69,000 (7)|
|Isoelectric point||5.0-5.5 (7)|
|Structure||single chain, NH2-terminal gla domain, four EGF domains|
|Percent carbohydrate||7% (7)|
|Post-translational modifications||one β-hydroxyaspartate (8) ten gla residues (7), three β-hydroxyasparagine (8)|
- Walker, F.J., Semin. Thromb. Hemostas., 10, 131 (1984).
- Dahlback, B., et al., Semin. Thromb. Hemostas., 10, 139 (1984).
- Walker, F.J., J. Biol. Chem., 256, 11128 (1981).
- Walker, F.J., J. Biol. Chem., 261, 10941 (1986).
- Jenny, R.J., et al., Prep. Biochem., 16, 227 (1986).
- Dahlback, B., Biochem. J., 209, 837 (1983).
- Discipio, R.G., et al., Biochemistry, 18, 899 (1979).
- Stenflo, J., et al., Proc. Natl. Acad. Sci. USA, 84, 368 (1987).
- Bajaj, S.P., et al., Prep. Biochem., 13, 191 (1983).
No sample publications.