Part:BBa_K4235000

Human Protein S Gene (PROS1)

Usage and Biology

Protein S is a vitamin K-dependent plasma protein that functions to prevent hypercoagulation of the blood. It serves as a non enzymatic cofactor for activated Protein C and is involved in the inactivation of coagulation factors Va and VIIIa. Protein S exists in two states in plasma, about 40% circulates as a free, functionally active form and the remaining 60% exists in the inactive form bound with C4b-binding protein. Protein S is secreted by hepatocytes, megakaryocytes, endothelial cells, etc. The initial form of secreted protein S is a 676 amino acid precursor protein, which undergoes a cleavage of a signal peptide present at the N-terminal, resulting in the mature 635 amino acid protein. Functionally active Protein S can directly bind to inhibit factor IXa, which activates factor X to Xa. Factor Xa and Va together form the prothrombinase complex responsible for activation of thrombin. Moreover, by acting as a cofactor for activated protein C, protein S promotes the cleavage of Factor VIIIa and Va, inhibiting the coagulation cascades.

Mutations in this gene (inherited as an autosomal dominant, homozygous or heterozygous fashion) cause non-functional or lower plasma levels of Protein S resulting in a Protein S deficiency. Individuals with Protein S deficiency are at an increased risk of developing abnormal blood clots, specifically in the smaller veins, known as venous thromboembolism. Two most common conditions associated with Protein S deficiency are deep vein thrombosis and pulmonary embolism. Although rare, infants with severe protein S deficiency can develop several blood clots throughout the body, resulting in a life threatening condition known as purpura fulminans. Moreover, severe COVID-19 infections are known to cause a decline in protein S levels, which further contributes to infection severity by causing extensive endothelial dysfunction and lung damage, which is a major cause of COVID-related mortality.

Sequence and Features

Assembly Compatibility:

• 10
  INCOMPATIBLE WITH RFC[10]

  Illegal EcoRI site found at 2028
  Illegal XbaI site found at 1341
  
• 12
  INCOMPATIBLE WITH RFC[12]

  Illegal EcoRI site found at 2028
  
• 21
  INCOMPATIBLE WITH RFC[21]

  Illegal EcoRI site found at 2028
  
• 23
  INCOMPATIBLE WITH RFC[23]

  Illegal EcoRI site found at 2028
  Illegal XbaI site found at 1341
  
• 25
  INCOMPATIBLE WITH RFC[25]

  Illegal EcoRI site found at 2028
  Illegal XbaI site found at 1341
  
• 1000
  COMPATIBLE WITH RFC[1000]

Bioinformatics: (protein modeling info from dry lab analysis)

Characterization and measurements: at least add a pcr gel picture.

Future Direction:

References:

U.S. National Library of Medicine. (n.d.). PROS1 protein S [homo sapiens (human)] - gene - NCBI. National Center for Biotechnology Information. Retrieved August 2, 2022, from https://www.ncbi.nlm.nih.gov/gene/5627

U.S. National Library of Medicine. (n.d.). CCDS report for consensus cds. National Center for Biotechnology Information. Retrieved August 2, 2022, from https://www.ncbi.nlm.nih.gov/CCDS/CcdsBrowse.cgi?REQUEST=CCDS&GO=MainBrowse&DATA=CCDS2923.1

Majumder, R., & Nguyen, T. (2021). Protein S: function, regulation, and clinical perspectives. Current opinion in hematology, 28(5), 339–344. https://doi.org/10.1097/MOH.0000000000000663

Pilli, V. S., Plautz, W., & Majumder, R. (2016). The Journey of Protein S from an Anticoagulant to a Signaling Molecule. JSM biochemistry and molecular biology, 3(1), 1014.