Human inter-α-inhibitor is a substrate for factor XIIIa and tissue transglutaminase

Biochim Biophys Acta. 2011 Dec;1814(12):1624-30. doi: 10.1016/j.bbapap.2011.08.017. Epub 2011 Sep 14.


In this study, we show that inter-α-inhibitor is a substrate for both factor XIIIa and tissue transglutaminase. These enzymes catalyze the incorporation of dansylcadaverine and biotin-pentylamine, revealing that inter-α-inhibitor contains reactive Gln residues within all three subunits. These findings suggest that transglutaminases catalyze the covalent conjugation of inter-α-inhibitor to other proteins. This was demonstrated by the cross-linking between inter-α-inhibitor and fibrinogen by either factor XIIIa or tissue transglutaminase. Finally, using quantitative mass spectrometry, we show that inter-α-inhibitor is cross-linked to the fibrin clot in a 1:20 ratio relative to the known factor XIIIa substrate α2-antiplasmin. This interaction may protect fibrin or other Lys-donating proteins from adventitious proteolysis by increasing the local concentration of bikunin. In addition, the reaction may influence the TSG-6/heavy Chain 2-mediated transfer of heavy chains observed during inflammation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alpha-Globulins / chemistry
  • Alpha-Globulins / metabolism*
  • Amino Acid Sequence
  • Animals
  • Catalytic Domain
  • Cross-Linking Reagents / pharmacology
  • Factor XIIIa / chemistry
  • Factor XIIIa / metabolism*
  • Factor XIIIa / physiology
  • Fibrinogen / chemistry
  • Fibrinogen / metabolism
  • Guinea Pigs
  • Humans
  • Models, Biological
  • Protein Binding
  • Protein Interaction Domains and Motifs
  • Protein Interaction Mapping
  • Protein Subunits / metabolism
  • Substrate Specificity
  • Transglutaminases / chemistry
  • Transglutaminases / metabolism*
  • Transglutaminases / physiology


  • Alpha-Globulins
  • Cross-Linking Reagents
  • Protein Subunits
  • inter-alpha-inhibitor
  • Fibrinogen
  • Factor XIIIa
  • Transglutaminases
  • transglutaminase 6, human