Factor XIII

Chr. 1 *q31-q32.1*
Chr. 1 q31-q32.1
Structures
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Structures	Swiss-model
Domains	InterPro

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Structures	Swiss-model
Domains	InterPro

Chr. 6 *p24.2-p23*
Chr. 6 p24.2-p23
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Structures	Swiss-model
Domains	InterPro

Factor XIII or fibrin stabilizing factor is a

crosslinks fibrin. Deficiency of XIII worsens clot stability and increases bleeding tendency.^[1]

Human XIII is a

B peptides. XIIIa is a dimer of activated A peptides.^[1]

Function

Within blood,

N-terminal activation peptides.^[1]

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.^[1]

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).^[1]

In humans,

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)

Genetics

Human factor XIII consist of A and B subunits. A subunit

3' UTR of 1.6 kbp. F13A1 exon(s)^[1]

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 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.^[1]

Structure

Factor XIII of human blood is a

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 as platelets. 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 83

C-terminal, residue numbers are in brackets):^[1]

activation peptide (1–37)

β-sandwich

(38–184)

catalytic domain (185–515), in which the residues C314, H373, D396 and W
279 partake in catalysis

β-barrel

1 (516–628)

β-barrel 2 (629–731)

B units are

disulfide bonds.^[1]

Physiology

A subunits of human factor XIII are made primarily by platelets and other cells of bone marrow origin. B subunits are secreted into blood by hepatocytes. 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 and half-life is 9–14 days.^[1]

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

Factor XIII deficiency

consanguineous marriage.^[3]

Diagnostic use

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

Discovery

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

References

^
S2CID 24703788
.

^
PMID 17842715
.

^ Dorgalaleh A, Naderi M, Hosseini MS, Alizadeh S, Hosseini S, Tabibian S, et al. (2015). "Factor XIII Deficiency in Iran: A Comprehensive Review of the Literature. Seminars in thrombosis and hemostasis". 41 (3): 323–29. {{cite journal}}: Cite journal requires |journal= (help)
^
S2CID 20424049
.

External links

[a-1] 
S2CID 24703788
.

[Laki-2] 
PMID 17842715
.

[3] Dorgalaleh A, Naderi M, Hosseini MS, Alizadeh S, Hosseini S, Tabibian S, et al. (2015). "Factor XIII Deficiency in Iran: A Comprehensive Review of the Literature. Seminars in thrombosis and hemostasis". 41 (3): 323–29. {{cite journal}}: Cite journal requires |journal= (help)

[Muszbek-4] 
S2CID 20424049
.

[1]

[2]

[3]

[4]

v t e Transferases: acyltransferases (EC 2.3)
2.3.1: other than amino-acyl groups	acetyltransferases: Acetyl-Coenzyme A acetyltransferase N-Acetylglutamate synthase Choline acetyltransferase Dihydrolipoyl transacetylase Acetyl-CoA C-acyltransferase Beta-galactoside transacetylase Chloramphenicol acetyltransferase N-acetyltransferase Serotonin N-acetyl transferase HGSNAT ARD1A Histone acetyltransferase P300/CBP NAT2 palmitoyltransferases: Carnitine O-palmitoyltransferase CPT1 CPT2 Serine C-palmitoyltransferase SPTLC1 SPTLC2 other: Acyltransferase like 2 Aminolevulinic acid synthase Beta-ketoacyl-ACP synthase Glyceronephosphate O-acyltransferase Lecithin—cholesterol acyltransferase Glycerol-3-phosphate O-acyltransferase 1-acylglycerol-3-phosphate O-acyltransferase 2-acylglycerol-3-phosphate O-acyltransferase ABHD5
2.3.2: Aminoacyltransferases	Gamma-glutamyl transpeptidase Peptidyl transferase Transglutaminase Tissue transglutaminase Keratinocyte transglutaminase Factor XIII
2.3.3: converted into alkyl on transfer	Citrate synthase Decylcitrate synthase Citrate (Re)-synthase Decylhomocitrate synthase 2-methylcitrate synthase 2-ethylmalate synthase 3-ethylmalate synthase ATP citrate lyase Malate synthase HMG-CoA synthase HMGCS2 2-hydroxyglutarate synthase 3-propylmalate synthase 2-isopropylmalate synthase Homocitrate synthase Sulfoacetaldehyde acetyltransferase

v t e Enzymes
Activity	Active site Binding site Catalytic triad Oxyanion hole Enzyme promiscuity Diffusion-limited enzyme Cofactor Enzyme catalysis
Regulation	Allosteric regulation Cooperativity Enzyme inhibitor Enzyme activator
Classification	EC number Enzyme superfamily Enzyme family List of enzymes
Kinetics	Enzyme kinetics Eadie–Hofstee diagram Hanes–Woolf plot Lineweaver–Burk plot Michaelis–Menten kinetics
Types	EC1 Oxidoreductases (list) EC2 Transferases (list) EC3 Hydrolases (list) EC4 Lyases (list) EC5 Isomerases (list) EC6 Ligases (list) EC7 Translocases (list)