GeneID: 181

Description:
This gene encodes protein S, a vitamin K-dependent protein with anticoagulant properties. It functions as a cofactor for the anticoagulant protease, activated protein C (APC), that inactivates the procoagulant factors Vα and VIIIα, thereby resulting in downregulation of thrombin formation. It is mainly produced by hepatocytes in the liver, but also by endothelial cells, megakaryocytes, osteoblasts, Leydig cells of testis, and vascular smooth muscle cells. It is found in two forms; either free in plasma or in complex with C4b-binding protein (complement regulator C4BP). Both forms bind to the negatively-charged phospholipid surface via an N-terminal Gla-domain (binding depends on calcium-induced folding of the Gla-domain), and modulate the coagulation and complement pathways, respectively. The bound form also stimulates phagocytosis of the apoptotic cells. Protein S plays a role in the regulation of fibrinolysis at the early stages of clot formation by inhibiting the activation of TAFI (thrombin activatable fibrinolysis inhibitor). Protein S is reported to have mitogenic activity, and to exert neuronal and vascular protective effects. Mutations in this gene result in autosomal dominant hereditary thrombophilia. A polymoprhism in this gene presents a risk factor of venous thrombosis in patients with HbH disease.

Synonyms: PSA , PROS , PS21 , PS22 , PS23 , PS24 , PS25 , THPH5 , THPH6

Comments:
N/A

Number of entries/variants: 1

1. Kanthou C, Benzakour O, Cellular effects and signalling pathways activated by the anti-coagulant factor, protein S, in vascular cells protein S cellular effects., Adv. Exp. Med. Biol. , 476(0), 155-66, 2000
2. Mosnier LO, Meijers JC, Bouma BN, The role of protein S in the activation of thrombin activatable fibrinolysis inhibitor (TAFI) and regulation of fibrinolysis., Thromb. Haemost. , 86(4), 1040-6, 2001
3. Liu D, Guo H, Griffin JH, Fernández JA, Zlokovic BV, Protein S confers neuronal protection during ischemic/hypoxic injury in mice., Circulation , 107(13), 1791-6, 2003
4. Rezende SM, Simmonds RE, Lane DA, Coagulation, inflammation, and apoptosis: different roles for protein S and the protein S-C4b binding protein complex., Blood , 103(4), 1192-201, 2004
5. Dahlbäck B, Villoutreix BO, The anticoagulant protein C pathway., FEBS Lett. , 579(15), 3310-6, 2005
6. Sun NA, Cheng P, Deng DH, Liu RR, Lai YR, Analysis of the genetic variants associated with recurrent thromboembolism in a patient with hemoglobin H disease following splenectomy: A case report., Biomed Rep , 5(1), 23-26, 2016