Human complement C3 is a substrate for transglutaminases. A functional link between non-protease-based members of the coagulation and complement cascades

Biochemistry. 2012 Jun 12;51(23):4735-42. doi: 10.1021/bi3004022. Epub 2012 Jun 4.


In this study, we report the finding of functional cross-talk between two non-protease components of the complement and coagulation cascades. We show that complement C3, a central component of the complement system, is associated with the fibrin clot and that C3 becomes covalently cross-linked to other proteins during coagulation. Enzymatic incorporation of dansylcadaverine and dansyl-PGGQQIV into C3 by coagulation factor XIIIa and tissue transglutaminase demonstrated that C3 is a transglutaminase substrate. This suggested that coagulation factor XIIIa covalently cross-links C3 to clot components during coagulation. Using mass spectrometry, we verified that C3 indeed is covalently associated with the fibrin clot in a ratio of 0.05:1 relative to the known coagulation factor XIIIa substrate α2-antiplasmin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Binding Sites
  • Blood Coagulation / physiology*
  • Catalysis
  • Complement Activation / physiology*
  • Complement C3 / metabolism*
  • Factor XIIIa / metabolism*
  • Humans
  • Plasma
  • Substrate Specificity
  • Thrombosis
  • Transglutaminases / metabolism*


  • Complement C3
  • Factor XIIIa
  • Transglutaminases