PS48 (PROS1) Protein

This gene encodes a vitamin K-dependent plasma protein that functions as a cofactor for the anticoagulant protease, activated protein C (APC) to inhibit blood coagulation. It is found in plasma in both a free, functionally active form and also in an inactive form complexed with C4b-binding protein. Mutations in this gene result in autosomal dominant hereditary thrombophilia. An inactive pseudogene of this locus is located at an adjacent region on chromosome 3. [provided by RefSeq, Feb 2009]

PROS1: Anticoagulant plasma protein; it is a cofactor to activated protein C in the degradation of coagulation factors Va and VIIIa. It helps to prevent coagulation and stimulating fibrinolysis. Defects in PROS1 are the cause of thrombophilia due to protein S deficiency, autosomal dominant (THPH5). A hemostatic disorder characterized by impaired regulation of blood coagulation and a tendency to recurrent venous thrombosis. However, many adults with heterozygous disease may be asymptomatic. Based on the plasma levels of total and free PROS1 antigen as well as the serine protease-activated protein C cofactor activity, three types of PROS1D have been described: type I, characterized by reduced total and free PROS1 antigen levels together with reduced anticoagulant activity; type III, in which only free PROS1 antigen and PROS1 activity levels are reduced; and the rare type II which is characterized by normal concentrations of both total and free PROS1 antigen, but low cofactor activity. Defects in PROS1 are the cause of thrombophilia due to protein S deficiency, autosomal recessive (THPH6). A very rare and severe hematologic disorder resulting in thrombosis and secondary hemorrhage usually beginning in early infancy. Some affected individuals develop neonatal purpura fulminans, multifocal thrombosis, or intracranial hemorrhage.

Protein type: Secreted, signal peptide; Secreted

Chromosomal Location of Human Ortholog: 3q11.2

Cellular Component: Golgi membrane; extracellular space; endoplasmic reticulum membrane; Golgi lumen; plasma membrane; extracellular region

Molecular Function: endopeptidase inhibitor activity; calcium ion binding

Biological Process: platelet activation; fibrinolysis; platelet degranulation; cellular protein metabolic process; regulation of complement activation; innate immune response; post-translational protein modification; blood coagulation; proteolysis; leukocyte migration; peptidyl-glutamic acid carboxylation

Disease: Thrombophilia Due To Protein S Deficiency, Autosomal Recessive; Thrombophilia Due To Protein S Deficiency, Autosomal Dominant