Primary structure of blood coagulation factor XIIIa (fibrinoligase, transglutaminase) from human placenta.
We have determined the primary structure of human placental factor XIIIa, an enzyme [fibrinoligase, transglutaminase, fibrin-stabilizing factor, EC 2.3.2.13 (protein-glutamine:amine gamma-glutamyltransferase)] that forms intermolecular isopeptide bonds between fibrin molecules as the last step in blood coagulation. Placental factor XIIIa is an unglycosylated polypeptide chain of 730 amino acid residues (Mr = 83,005) that appears to be identical to the a subunit of the plasma zymogen factor XIII. Ca2+-dependent activation of factor XIIIa by thrombin removes a blocked amino-terminal peptide and unmasks a reactive thiol group at Cys-314. A second specific cleavage after Lys-513 by thrombin inactivates factor XIIIa and produces an amino-terminal 56-kDa fragment and a 24-kDa fragment. The amino acid sequence of factor XIIIa is unique and does not exhibit internal homology, but its active center is similar to that of the thiol proteases. The probable Ca2+-binding site of factor XIIIa has been identified by homology to the high-affinity sites in calmodulins. Knowledge of the primary structure of factor XIIIa will aid elucidation of the mechanism of its enzymatic action and that of the many tissue transglutaminases of which it is the prototype. This will also facilitate production of factor XIIIa by recombinant DNA technology for use in treatment of congenital factor XIII deficiencies and in the postoperative healing of wounds.
D000595:Amino Acid Sequence; D000596:Amino Acids / Q000032:analysis; D001483:Base Sequence; D001665:Binding Sites; D001792:Blood Platelets / Q000032:analysis; D002118:Calcium / Q000378:metabolism; D003545:Cysteine / Q000032:analysis; D004247:DNA / Q000032:analysis; D005176:Factor XIII / Q000032:analysis*; D005260:Female; D006801:Humans; D008958:Models, Molecular; D010920:Placenta / Q000201:enzymology*; D011247:Pregnancy; D011487:Protein Conformation; D013917:Thrombin / Q000494:pharmacology; D011503:Transglutaminases
D000596:Amino Acids; D004247:DNA; D005176:Factor XIII; D011503:Transglutaminases; D013917:Thrombin; D003545:Cysteine; D002118:Calcium