Factor XIII or fibrin stabilizing factor is a zymogen found in blood of humans and some other animals. It is activated by thrombin to factor XIIIa. Factor XIIIa is an enzyme of the blood coagulation system that crosslinks fibrin. Deficiency of XIII worsens clot stability and increases bleeding tendency. Human XIII is a heterotetramer. It consists of 2 enzymatic A peptides and 2 non-enzymatic B peptides. XIIIa is a dimer of activated A peptides. Function Within blood, thrombins cleave fibrinogens to fibrins during coagulation and a fibrin-based blood clot forms. Factor XIII is a transglutaminase that circulates in human blood as a heterotetramer of two A and two B subunits. Factor XIII binds to the clot via their B units. In the presence of fibrins, thrombin efficiently cleaves the R37–G38 peptide bond of each A unit within a XIII tetramer. A units release their N-terminal activation peptides. Both of the non-covalently bound B units are now able to dissociate from the tetramer with the help of calcium ions (Ca2+) in the blood; these ions also activate the remaining dimer of two A units via a conformational change. Factor XIIIa (dimer of two active A units) crosslinks fibrins within the clot by forming isopeptide bonds between various glutamines and lysines of the fibrins. These bonds make the clot physically more durable and protect it from premature enzymatic degradation (fibrinolysis). In humans, plasmin, antithrombin and TFPI are the most relevant proteolytic inhibitors of the active factor XIIIa. α2-macroglobulin is a significant non-proteolytic inhibitor. Genetics Human factor XIII consist of A and B subunits. A subunit gene is F13A1. It is on the chromosome 6 at the position 6p24–25. It spans over 160 kbp, has 14 introns and 15 exons. Its mRNA is 3.9 kbp. It has a 5' UTR of 84 bp and a 3' UTR of 1.6 kbp. F13A1 exon(s) 1 code 5' UTR 2 code activation peptide 2–4 code β-sandwich 4–12 code catalytic domain 12–13 code β-barrel 1 13–15 code β-barrel 2 B subunit gene is F13B. It is on the chromosome 1 at the position 1q31–32.1. It spans 28 kpb, has 11 introns and 12 exons. Its mRNA is 2.2 kbp. Exon 1 codes 5' UTR. Exons 2–12 code the 10 different sushi domains. Structure Factor XIII of human blood is a heterotetramer of two A and two B linear polypeptides or "units". A units are potentially catalytic; B