What is the role of C4BP in the pathophysiology of protein S deficiency?

Updated: Jan 03, 2021
  • Author: Mohammad Muhsin Chisti, MD, FACP; Chief Editor: Perumal Thiagarajan, MD  more...
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In blood plasma, protein S exists in both a bound and a free state. A portion of protein S is noncovalently bound with high affinity to the complement regulatory protein C4b-binding protein (C4BP). The C4BP molecule consists of 7 alpha chains that bind to the complement protein, C4b, and one beta chain. The beta chain of the C4bBP molecules contains the binding sites for protein S. There is emerging evidence in the role of Protein S in the complement pathway. It is now found to interact with the complement system and may play a role in phagocytosis of apoptotic cells. Protein S interacts with tyrosine kinase receptors of the TAM family, along with phosphatidyl serine on cell surface apoptotic cells which stimulates macrophage phagocytosis of these cells. [9, 10]  The physiological impact of protein S deficiencies on these nonanticoagulant roles of protein S is not yet known.

APC and protein S require negatively charged phospholipids (PL) and Ca2+ for normal anticoagulant activity. Studies of the structure and function relationships of protein S demonstrate that the APC interaction sites are located in the Gla, TSR, and first EGF-like modules of protein S. The binding site for C4BP is located in the SHBG-like region, which is also important for full anticoagulant activity.

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