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Related Concept Videos

General Transcription Factors01:30

General Transcription Factors

Tissue-specific transcription factors contribute to diverse cellular functions in mammals. For example, the gene for beta globin, a major component of hemoglobin, is present in all cells of the body. However, it is only expressed in red blood cells because the transcription factors that can bind to the promoter sequences of the beta globin gene are only expressed in these cells. Tissue-specific transcription factors also ensure that mutations in these factors may impair only the function of...
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Cofactors and Coenzymes

Enzymes require additional components for proper function. There are two such classes of molecules: cofactors and coenzymes. Cofactors are metallic ions and coenzymes are non-protein organic molecules. Both of these types of helper molecule can be tightly bound to the enzyme or bound only when the substrate binds.
Cofactors and Coenzymes01:24

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Phosphoinositides and PIPs

Phosphoinositides are a group of phospholipids containing a glycerol backbone with two fatty acid chains and a phosphate attached to a myoinositol sugar ring. The inositol head group extends into the cytoplasm, where it is modified by adding phosphate groups to form phosphatidylinositol phosphates or PIPs.
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Related Experiment Video

Updated: Jun 21, 2026

Extracellular Vesicle Tissue Factor Activity Assay
03:53

Extracellular Vesicle Tissue Factor Activity Assay

Published on: December 29, 2023

Protein S as cofactor for TFPI.

Tilman M Hackeng1, Jan Rosing

  • 1Department of Biochemistry, Cardiovascular Research Institute Maastricht, University Maastricht, Maastricht, The Netherlands.

Arteriosclerosis, Thrombosis, and Vascular Biology
|August 8, 2009
PubMed
Summary
This summary is machine-generated.

Protein S exhibits anticoagulant activity independently of activated protein C (APC). It functions as a cofactor for tissue factor pathway inhibitor (TFPI), enhancing the inhibition of factor Xa, particularly under low procoagulant conditions.

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Published on: August 26, 2012

Area of Science:

  • Biochemistry
  • Hematology
  • Molecular Biology

Background:

  • Protein S traditionally known as a cofactor for activated protein C (APC) in coagulation regulation.
  • Emerging evidence suggests APC-independent anticoagulant functions of protein S.
  • Distinguishing between APC-dependent and independent activities has been challenging due to complex mechanisms.

Purpose of the Study:

  • To elucidate the mechanisms behind protein S's APC-independent anticoagulant activity.
  • To differentiate between observed activities in model systems versus plasma.
  • To identify the specific molecular interactions mediating protein S's anticoagulant effects.

Main Methods:

  • Analysis of protein S activity in phospholipid-dependent model systems.
  • Investigation of protein S anticoagulant function in plasma.
  • Assays to determine the role of protein S in the tissue factor pathway inhibitor (TFPI) system.

Main Results:

  • APC-independent activity in model systems attributed to protein S multimers inhibiting phospholipid binding.
  • In plasma, protein S's anticoagulant activity is independent of phospholipid concentration but dependent on tissue factor (TF) levels.
  • Protein S identified as a cofactor for TFPI, enhancing the inhibition of factor Xa by approximately 10-fold.

Conclusions:

  • Protein S possesses a distinct APC-independent anticoagulant function mediated by its role as a TFPI cofactor.
  • This TFPI/protein S system is particularly effective in inhibiting the tissue factor pathway under conditions of low procoagulant stimuli.
  • Understanding this pathway offers new insights into hemostasis and potential therapeutic targets.