Coagulation factor XIII A chain explained

Coagulation factor XIII A chain, (FXIIIa) is a protein that in humans is encoded by the F13A1 gene.

Function

This gene encodes the coagulation factor XIII A subunit. Coagulation factor XIII is the last zymogen to become activated in the blood coagulation cascade. Plasma factor XIII is a heterotetramer composed of 2 A subunits and 2 B subunits. The A subunits have catalytic function, and the B subunits do not have enzymatic activity and may serve as plasma carrier molecules. Platelet factor XIII is composed of just 2 A subunits, which are identical to those of plasma origin. Upon cleavage of the activation peptide by thrombin and in the presence of calcium ion, the plasma factor XIII dissociates its B subunits and yields the same active enzyme, factor XIIIa, as platelet factor XIII. This enzyme acts as a transglutaminase to catalyze the formation of gamma-glutamyl-epsilon-lysine crosslinking between fibrin molecules, thus stabilizing the fibrin clot. It also crosslinks alpha-2-plasmin inhibitor, or fibronectin, to the alpha chains of fibrin. Factor XIII deficiency is classified into two categories: type I deficiency, characterized by the lack of both the A and B subunits; and type II deficiency, characterized by the lack of the A subunit alone. These defects can result in a lifelong bleeding tendency, defective wound healing, and habitual abortion.^[1]

Interactions

Coagulation factor XIII A chain has been shown to interact with coagulation factor XIII B chain.^{[2] [3]}

Further reading

• Adány R . Intracellular factor XIII: cellular distribution of factor XIII subunit a in humans. . Semin. Thromb. Hemost. . 22 . 5 . 399–408 . 1997 . 8989823 . 10.1055/s-2007-999038 . 22915173 .
• Adány R, Bárdos H . Factor XIII subunit A as an intracellular transglutaminase. . Cell. Mol. Life Sci. . 60 . 6 . 1049–60 . 2003 . 12861374 . 10.1007/s00018-003-2178-9 . 7831538 . 11138545 .
• Bereczky Z, Katona E, Muszbek L . Fibrin stabilization (factor XIII), fibrin structure and thrombosis. . Pathophysiol. Haemost. Thromb. . 33 . 5–6 . 430–7 . 2005 . 15692256 . 10.1159/000083841 . 12156307 .
• Board P, Coggan M, Miloszewski K . Identification of a point mutation in factor XIII A subunit deficiency. . Blood . 80 . 4 . 937–41 . 1992 . 1353995 . 10.1182/blood.V80.4.937.937. free .
• Kamura T, Okamura T, Murakawa M, Tsuda H, Teshima T, Shibuya T, Harada M, Niho Y . Deficiency of coagulation factor XIII A subunit caused by the dinucleotide deletion at the 5' end of exon III. . J. Clin. Invest. . 90 . 2 . 315–9 . 1992 . 1644910 . 443104 . 10.1172/JCI115864 .
• Harsfalvi J, Fesus L, Tarcsa E, Laczko J, Loewy AG . The presence of a covalently cross-linked matrix in human platelets. . Biochim. Biophys. Acta . 1073 . 2 . 268–74 . 1991 . 2009280 . 10.1016/0304-4165(91)90131-Y .
• Bishop PD, Teller DC, Smith RA, Lasser GW, Gilbert T, Seale RL . Expression, purification, and characterization of human factor XIII in Saccharomyces cerevisiae. . Biochemistry . 29 . 7 . 1861–9 . 1990 . 2184890 . 10.1021/bi00459a028 .
• Hilgenfeld R, Liesum A, Storm R, Metzner HJ, Karges HE . Crystallization of blood coagulation factor XIII by an automated procedure. . FEBS Lett. . 265 . 1–2 . 110–2 . 1990 . 2365049 . 10.1016/0014-5793(90)80896-Q . 23295980 . free .
• Carrell NA, Erickson HP, McDonagh J . Electron microscopy and hydrodynamic properties of factor XIII subunits. . J. Biol. Chem. . 264 . 1 . 551–6 . 1989 . 10.1016/S0021-9258(17)31294-2 . 2491853 . free .
• Takahashi N, Takahashi Y, Putnam FW . Primary structure of blood coagulation factor XIIIa (fibrinoligase, transglutaminase) from human placenta. . Proc. Natl. Acad. Sci. U.S.A. . 83 . 21 . 8019–23 . 1986 . 2877456 . 386858 . 10.1073/pnas.83.21.8019 . 1986PNAS...83.8019T . free .
• Grundmann U, Amann E, Zettlmeissl G, Küpper HA . Characterization of cDNA coding for human factor XIIIa. . Proc. Natl. Acad. Sci. U.S.A. . 83 . 21 . 8024–8 . 1986 . 2877457 . 386859 . 10.1073/pnas.83.21.8024 . 1986PNAS...83.8024G . free .
• Ichinose A, Davie EW . Characterization of the gene for the a subunit of human factor XIII (plasma transglutaminase), a blood coagulation factor. . Proc. Natl. Acad. Sci. U.S.A. . 85 . 16 . 5829–33 . 1988 . 2901091 . 281858 . 10.1073/pnas.85.16.5829 . 1988PNAS...85.5829I . free .
• Board PG, Webb GC, McKee J, Ichinose A . Localization of the coagulation factor XIII A subunit gene (F13A) to chromosome bands 6p24----p25. . Cytogenet. Cell Genet. . 48 . 1 . 25–7 . 1988 . 2903011 . 10.1159/000132580 .
• Ichinose A, Hendrickson LE, Fujikawa K, Davie EW . Amino acid sequence of the a subunit of human factor XIII. . Biochemistry . 25 . 22 . 6900–6 . 1987 . 3026437 . 10.1021/bi00370a025 .
• Takagi T, Doolittle RF . Amino acid sequence studies on factor XIII and the peptide released during its activation by thrombin. . Biochemistry . 13 . 4 . 750–6 . 1974 . 4811064 . 10.1021/bi00701a018 .
• Yee VC, Pedersen LC, Bishop PD, Stenkamp RE, Teller DC . Structural evidence that the activation peptide is not released upon thrombin cleavage of factor XIII. . Thromb. Res. . 78 . 5 . 389–97 . 1995 . 7660355 . 10.1016/0049-3848(95)00072-Y .
• Coggan M, Baker R, Miloszewski K, Woodfield G, Board P . Mutations causing coagulation factor XIII subunit A deficiency: characterization of the mutant proteins after expression in yeast. . Blood . 85 . 9 . 2455–60 . 1995 . 7727776 . 10.1182/blood.V85.9.2455.bloodjournal8592455. free .
• Kaczmarek E, Liu Y, Berse B, Chen CS, McDonagh J . Biosynthesis of plasma factor XIII: evidence for transcription and translation in hepatoma cells. . Biochim. Biophys. Acta . 1247 . 1 . 127–34 . 1995 . 7873582 . 10.1016/0167-4838(94)00167-f .
• Yee VC, Pedersen LC, Le Trong I, Bishop PD, Stenkamp RE, Teller DC . Three-dimensional structure of a transglutaminase: human blood coagulation factor XIII. . Proc. Natl. Acad. Sci. U.S.A. . 91 . 15 . 7296–300 . 1994 . 7913750 . 44386 . 10.1073/pnas.91.15.7296 . 1994PNAS...91.7296Y . free .
• Suzuki K, Iwata M, Ito S, Matsui K, Uchida A, Mizoi Y . Molecular basis for subtypic differences of the "a" subunit of coagulation factor XIII with description of the genesis of the subtypes. . Hum. Genet. . 94 . 2 . 129–35 . 1994 . 7913909 . 10.1007/bf00202857 . 20800219 .

Notes and References

1. Web site: Entrez Gene: F13A1 coagulation factor XIII, A1 polypeptide.
2. Carrell NA, Erickson HP, McDonagh J . Electron microscopy and hydrodynamic properties of factor XIII subunits . J. Biol. Chem. . 264 . 1 . 551–6 . Jan 1989 . 10.1016/S0021-9258(17)31294-2 . 2491853 . free .
3. Achyuthan KE, Rowland TC, Birckbichler PJ, Lee KN, Bishop PD, Achyuthan AM . Hierarchies in the binding of human factor XIII, factor XIIIa, and endothelial cell transglutaminase to human plasma fibrinogen, fibrin, and fibronectin . Mol. Cell. Biochem. . 162 . 1 . 43–9 . Sep 1996 . 8905624 . 10.1007/bf00250994 . 23583301 .