coagulation factor XIII, A1 polypeptide
Inactive A1 peptide homodimer with all of the domains and main catalytic residues shown with different colors.
Identifiers
Symbol	F13A1
Alt. symbols	F13A
NCBI gene	2162
HGNC	3531
OMIM	134570
RefSeq	NM_000129
UniProt	P00488
Other data
EC number	2.3.2.13
Locus	Chr. 6p24.2-p23
Search for Structures Swiss-model Domains InterPro

Factor XIII, orfibrin stabilizing factor, is aplasma protein andzymogen. It is activated bythrombin tofactor XIIIa whichcrosslinksfibrin incoagulation. Deficiency of XIII worsens clot stability and increases bleeding tendency.^[1]

Human XIII is aheterotetramer. It consists of 2 enzymaticA peptides and 2 non-enzymaticB peptides. XIIIa is adimer of activated A peptides.^[1]

Within blood,thrombins cleavefibrinogens to fibrins during coagulation and a fibrin-based blood clot forms. Factor XIII is atransglutaminase that circulates in human blood as aheterotetramer 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 theR37–G38peptide bond of each A unit within a XIII tetramer. A units release theirN-terminal activationpeptides.^[1]

Both of the non-covalently bound B units are now able to dissociate from the tetramer with the help ofcalcium ions (Ca²⁺) in the blood; these ions also activate the remaining dimer of two A units via a conformational change.^[1]

Factor XIIIa (dimer of two active A units)crosslinks fibrins within the clot by formingisopeptide bonds between variousglutamines andlysines of the fibrins. These bonds make the clot physically more durable and protect it from premature enzymatic degradation (fibrinolysis).^[1]

In humans,plasmin,antithrombin andTFPI are the most relevant proteolytic inhibitors of the active factor XIIIa.α2-macroglobulin is a significant non-proteolytic inhibitor.^[1]

• 
  Activation peptides (pink) of A units are removed by thrombin (IIa) in the presence of fibrin. B units (gray) are released with the help of calcium and A unit dimer is activated (XIIIa forms).
• 
  XIIIa crosslinks fibrin (simplified picture)

Human factor XIII consist of A and B subunits. A subunitgene isF13A1. It is onchromosome 6 at the position 6p24–25. It spans over 160kbp, has 14introns and 15exons. ItsmRNA is 3.9 kbp. It has a5' UTR of 84 bp and a3' UTR of 1.6 kbp.F13A1 exon(s)^[1]

• 1 code 5' UTR
• 2 code activation peptide
• 2–4 codeβ-sandwich
• 4–12 codecatalytic domain
• 12–13 codeβ-barrel 1
• 13–15 code β-barrel 2

B subunit gene isF13B. It is onchromosome 1 at the position 1q31–32.1. It spans 28 kbp, has 11 introns and 12 exons. Its mRNA is 2.2 kbp. Exon 1 codes 5' UTR. Exons 2–12 code the 10 differentsushi domains.^[1]

Factor XIII of human blood is aheterotetramer of two A and two B linear polypeptides or "units". A units are potentially catalytic; B units are not. A units form adimeric center. Non-covalently bound B units form a ring-like structure around the center. B units are removed when XIII is activated to XIIIa. Dimers containing only A units also occur within cells such asplatelets. Large quantities of singular B units (monomers) also occur within blood. These dimers and monomers are not known to participate in coagulation, whereas the tetramers do.^[1]

A units have a mass of about 83kDa, 731amino acid residues, 5protein domains (listed from theN-terminal toC-terminal, residue numbers are in brackets):^[1]

• activation peptide (1–37)
• β-sandwich (38–184)
• catalytic domain (185–515), in which the residuesC314,H373,D396 andW279 partake in catalysis
• β-barrel 1 (516–628)
• β-barrel 2 (629–731)

B units areglycoproteins. Each has a mass of about 80 kDa (8.5% of the mass is fromcarbohydrates), 641 residues and 10sushi domains. Each domain has about 60 residues and 2 internaldisulfide bonds.^[1]

A subunits of human factor XIII are made primarily byplatelets and other cells ofbone marrow origin. B subunits are secreted into blood byhepatocytes. A and B units combine within blood to form heterotetramers of two A units and two B units.Blood plasma concentration of the heterotetramers is 14–48 mg/L andhalf-life is 9–14 days.^[1]

A clot that has not been stabilized by FXIIIa is soluble in 5 mol/Lurea, while a stabilized clot is resistant to this phenomenon.^[2]

Factor XIII deficiency, while generally rare, does occur, withIran having the highest global incidence of the disorder with 473 cases. The city ofKhash, located inSistan andBalochistan provinces, has the highest incidence in Iran, with a high rate ofconsanguineous marriage.^[3]

Factor XIII levels are not measured routinely, but may be considered in patients with an unexplained bleeding tendency. As the enzyme is quite specific formonocytes andmacrophages, determination of the presence of factor XIII may be used to identify and classify malignant diseases involving these cells.^[4]

Factor XIII Deficiency is also known as Laki–Lorand factor, afterKalman Laki andLaszlo Lorand, the scientists who first proposed its existence in 1948.^[2] A 2005 conference recommended standardization of nomenclature.^[4]

• Catridecacog
• Coagulation
• D-dimer
• Factor XIII deficiency

• Factor XIII deficiency at hemophilia.org
• med/3491 ateMedicine

• Genes on human chromosome 6
• Genes on human chromosome 1
• Coagulation system
• EC 2.3.2
• Zymogens

• CS1 errors: missing periodical
• Articles with short description
• Short description matches Wikidata
• Protein pages needing a picture