|
 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.
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.
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Properties
of Protein S |
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Localization:
|
Plasma, free and complexed to C4BP |
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Plasma concentration:
|
10 µg/ml (free) (6) |
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Mode of action:
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Cofactor for activated protein C |
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Molecular weight:
|
69,000 (7) |
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Extinction coefficient:
|
|
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Isoelectric point:
|
5.0-5.5 (7) |
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Structure:
|
single chain, NH2-terminal gla domain, four EGF domains |
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Percent carbohydrate:
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7% (7) |
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Post translational modifications:
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one
β-hydroxyaspartate (8) ten gla residues (7), three
β-hydroxyasparagine (8) |
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Catalog
Number |
Description |
|
HCPS-0090 |
Human Protein S |
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References
1. Walker, F.J., Semin. Thromb. Hemostas., 10, 131 (1984).
2. Dahlback, B., et al., Semin. Thromb. Hemostas., 10, 139 (1984).
3. Walker, F.J., J. Biol. Chem., 256, 11128 (1981).
4. Walker, F.J., J. Biol. Chem., 261, 10941 (1986).
5. Jenny, R.J., et al., Prep. Biochem., 16, 227 (1986).
6. Dahlback, B., Biochem. J., 209, 837 (1983).
7. Discipio, R.G., et al., Biochemistry, 18, 899 (1979).
8. Stenflo, J., et al., Proc. Natl. Acad. Sci. USA, 84, 368 (1987).
9. Bajaj, S.P., et al., Prep. Biochem., 13, 191 (1983).
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