Coagulation Factor XIIIa Substrates in Human Plasma. Identification and Incorporation Into the Clot

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Coagulation factor XIIIa (FXIIIa) is a transglutaminase with a well-defined role in the final stages of blood coagulation. The active enzyme catalyzes the formation of ε-(γ-glutamyl)lysine isopeptide bonds between specific Gln and Lys residues. The primary physiological outcome of this catalytic activity is stabilization of the fibrin clot during coagulation. The stabilization is achieved through the introduction of cross-links between fibrin monomers and through cross-linking of proteins with anti-fibrinolytic activity to fibrin. FXIIIa additionally cross-links several proteins with other functionalities to the clot. Cross-linking of proteins to the clot is generally believed to modify clot characteristics such as proteolytic susceptibility and hereby affect the outcome of tissue damage. In the present study, we use a proteomic approach in combination with transglutaminase-specific labeling to identify FXIIIa plasma protein substrates and their reactive residues. The results revealed a total of 147 FXIIIa substrates of which 132 have not previously been described. We confirm that 48 of the FXIIIa substrates were indeed incorporated into the insoluble fibrin clot during the coagulation of plasma. The identified substrates are involved in among others complement activation, coagulation, inflammatory and immune responses and extracellular matrix organization.
Original languageEnglish
JournalJournal of Biological Chemistry
Volume289
Pages (from-to)6526-6534
Number of pages9
ISSN0021-9258
DOIs
Publication statusPublished - 7 Mar 2014

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