Protein S

Protein S

Protein S is a vitamin K-dependent plasma glycoprotein synthesized in the liver. In the circulation, Protein S exists in two forms: a free form and a complex form bound to complement protein C4b.


The best characterized function of Protein S is its role in the anti coagulation pathway, it functions as a cofactor to Protein C in the inactivation of Factors Va and VIIIa. Only the free form has cofactor activity.

Protein S can bind to negatively charged phospholipids via the carboxylated GLA domain. This property allows Protein S to function in the removal of cells which are undergoing apoptosis. Apoptosis is a form of cell death that is used by the body to remove unwanted or damaged cells from tissues. Cells which are apoptotic (ie. in the process of apoptosis) no longer actively manage the distribution of phospholipids in their outer membrane and hence begin to display negatively charged phospholipids, such as phosphatidyl serine, on the cell surface. In healthy cells, an ATP (Adenosine triphosphate)-dependent enzyme removes these from the outer leaflet of the cell membrane. These negatively charged phospholipids are recognized by phagocytes such as macrophages. Protein S can bind to the negatively charged phospholipids and function as a bridging molecule between the apoptotic cell and the phagocyte. The bridging property of Protein S enhances the phagocytosis of the apoptotic cell, allowing it to be removed 'cleanly' without any symptoms of tissue damage such as inflammation occurring.


Protein S deficiency is a rare blood disorder which can lead to an increased risk of thrombosis.

ee also

* hemostasis

Further reading

citations =
*cite journal | author=Dahlbäck B |title=Protein S and C4b-binding protein: components involved in the regulation of the protein C anticoagulant system |journal=Thromb. Haemost. |volume=66 |issue= 1 |pages= 49–61 |year= 1991 |pmid= 1833851 |doi=
*cite journal | author=Witt I |title= [Molecular biological basis and diagnosis of hereditary defect of antithrombin III, protein c and protein S] |journal=Hamostaseologie |volume=22 |issue= 2 |pages= 14–24 |year= 2002 |pmid= 12193972 |doi= 10.1267/Hamo02020057 |doi_brokendate=2008-06-22
*cite journal | author=Rezende SM, Simmonds RE, Lane DA |title=Coagulation, inflammation, and apoptosis: different roles for protein S and the protein S-C4b binding protein complex |journal=Blood |volume=103 |issue= 4 |pages= 1192–201 |year= 2004 |pmid= 12907438 |doi= 10.1182/blood-2003-05-1551
*cite journal | author=Dahlbäck B |title=The tale of protein S and C4b-binding protein, a story of affection |journal=Thromb. Haemost. |volume=98 |issue= 1 |pages= 90–6 |year= 2007 |pmid= 17597997 |doi=
*cite journal | author=García de Frutos P, Fuentes-Prior P, Hurtado B, Sala N |title=Molecular basis of protein S deficiency |journal=Thromb. Haemost. |volume=98 |issue= 3 |pages= 543–56 |year= 2007 |pmid= 17849042 |doi=
*cite journal | author=Maillard C, Berruyer M, Serre CM, "et al." |title=Protein-S, a vitamin K-dependent protein, is a bone matrix component synthesized and secreted by osteoblasts |journal=Endocrinology |volume=130 |issue= 3 |pages= 1599–604 |year= 1992 |pmid= 1531628 |doi=10.1210/en.130.3.1599
*cite journal | author=Griffin JH, Gruber A, Fernández JA |title=Reevaluation of total, free, and bound protein S and C4b-binding protein levels in plasma anticoagulated with citrate or hirudin |journal=Blood |volume=79 |issue= 12 |pages= 3203–11 |year= 1992 |pmid= 1534488 |doi=
*cite journal | author=Guglielmone HA, Vides MA |title=A novel functional assay of protein C in human plasma and its comparison with amidolytic and anticoagulant assays |journal=Thromb. Haemost. |volume=67 |issue= 1 |pages= 46–9 |year= 1992 |pmid= 1615482 |doi=
*cite journal | author=Bertina RM, Ploos van Amstel HK, van Wijngaarden A, "et al." |title=Heerlen polymorphism of protein S, an immunologic polymorphism due to dimorphism of residue 460 |journal=Blood |volume=76 |issue= 3 |pages= 538–48 |year= 1990 |pmid= 2143091 |doi=
*cite journal | author=Schmidel DK, Tatro AV, Phelps LG, "et al." |title=Organization of the human protein S genes |journal=Biochemistry |volume=29 |issue= 34 |pages= 7845–52 |year= 1991 |pmid= 2148110 |doi=10.1021/bi00486a010
*cite journal | author=Ploos van Amstel HK, Reitsma PH, van der Logt CP, Bertina RM |title=Intron-exon organization of the active human protein S gene PS alpha and its pseudogene PS beta: duplication and silencing during primate evolution |journal=Biochemistry |volume=29 |issue= 34 |pages= 7853–61 |year= 1991 |pmid= 2148111 |doi=10.1021/bi00486a011
*cite journal | author=Allaart CF, Aronson DC, Ruys T, "et al." |title=Hereditary protein S deficiency in young adults with arterial occlusive disease |journal=Thromb. Haemost. |volume=64 |issue= 2 |pages= 206–10 |year= 1991 |pmid= 2148653 |doi=
*cite journal | author=Ohlin AK, Landes G, Bourdon P, "et al." |title=Beta-hydroxyaspartic acid in the first epidermal growth factor-like domain of protein C. Its role in Ca2+ binding and biological activity |journal=J. Biol. Chem. |volume=263 |issue= 35 |pages= 19240–8 |year= 1989 |pmid= 2461936 |doi=
*cite journal | author=Schwarz HP, Heeb MJ, Lottenberg R, "et al." |title=Familial protein S deficiency with a variant protein S molecule in plasma and platelets |journal=Blood |volume=74 |issue= 1 |pages= 213–21 |year= 1989 |pmid= 2526663 |doi=
*cite journal | author=Ploos van Amstel HK, van der Zanden AL, Reitsma PH, Bertina RM |title=Human protein S cDNA encodes Phe-16 and Tyr 222 in consensus sequences for the post-translational processing |journal=FEBS Lett. |volume=222 |issue= 1 |pages= 186–90 |year= 1987 |pmid= 2820795 |doi=10.1016/0014-5793(87)80217-X
*cite journal | author=Dahlbäck B, Lundwall A, Stenflo J |title=Primary structure of bovine vitamin K-dependent protein S |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=83 |issue= 12 |pages= 4199–203 |year= 1986 |pmid= 2940598 |doi=10.1073/pnas.83.12.4199
*cite journal | author=Lundwall A, Dackowski W, Cohen E, "et al." |title=Isolation and sequence of the cDNA for human protein S, a regulator of blood coagulation |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=83 |issue= 18 |pages= 6716–20 |year= 1986 |pmid= 2944113 |doi=10.1073/pnas.83.18.6716
*cite journal | author=Engesser L, Broekmans AW, Briët E, "et al." |title=Hereditary protein S deficiency: clinical manifestations |journal=Ann. Intern. Med. |volume=106 |issue= 5 |pages= 677–82 |year= 1987 |pmid= 2952034 |doi=
*cite journal | author=Watkins PC, Eddy R, Fukushima Y, "et al." |title=The gene for protein S maps near the centromere of human chromosome 3 |journal=Blood |volume=71 |issue= 1 |pages= 238–41 |year= 1988 |pmid= 2961379 |doi=

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