Factor XIII

Factor XIII crosslinks fibrin

coagulation factor XIII, A1 polypeptide
Identifiers
Symbol	F13A1
Alt. symbols	F13A
Entrez	2162
HUGO	3531
OMIM	134570
RefSeq	NM_000129
UniProt	P00488
Other data
Locus	Chr. 6 p24.2-p23

coagulation factor XIII, B polypeptide
Identifiers
Symbol	F13B
Entrez	2165
HUGO	3534
OMIM	134580
RefSeq	NM_001994
UniProt	P05160
Other data
Locus	Chr. 1 q31-q32.1

Factor XIII or fibrin stabilizing factor is an enzyme (EC 2.3.2.13) of the blood coagulation system that crosslinks fibrin. Deficiency of this factor (FXIIID) affects clot stability. FXIIID, while generally rare, Iran has the highest global incidence of disorder with 473 cases; the city of Khash has the highest incidence in Iran, as it is in Sistan and Balochistan provinces with high rate of consanguineous marriage.^[1]

Function

Factor XIII is a transglutaminase that circulates in the plasma as a heterotetramer of two catalytic A subunits and two carrier B subunits. When thrombin has converted fibrinogen to fibrin, the latter forms a proteinaceous network in which every E-unit is crosslinked to only one D-unit. Factor XIII is activated by thrombin into factor XIIIa; its activation into Factor XIIIa requires calcium as a cofactor. A cleavage by thrombin between residue Arg37 and Gly38 on the N-terminus of the A subunit, leads to the release of the activation peptide (MW 4000 da). In the presence of calcium the carrier subunits dissociate from the catalytic subunits, leading to a 3D change in conformation of factor XIII and hence the exposure of catalytic cysteine residue. Upon activation by thrombin, factor XIIIa acts on fibrin to form γ-glutamyl-Є-lysyl amide cross links between fibrin molecules to form an insoluble clot.

Discovery

FXIII is known also 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.^[3]

Genetics

Zymogen factor XIII is a 320kDa glycoprotein tetramer consisting of twice two subunits (2 A and 2 B),^[3] the genes for which are on different chromosomes:

A subunit (6p25-p24). The transglutaminase part; this adds an alkyl group to the nitrogen on a glutamine residue, which binds in turn with a lysine on the other chain. The molecular weight of the A chain is approximately 83kDa.
B subunit (1q31-q32.1). This has no clear enzymatic activity, and may serve as a carrier for the A subunit. The molecular weight of the B chain is approximately 76.5kDa.

Physiology

Typical concentrations of FXIII in plasma is 10 μg/ml (2A2B heterodimer), while the concentration of free B chain is 22 μg/ml. FXIII has a long half-life, ranging from 5 to 9 days. It is present in plasma, platelets, and monocytes, as well as macrophages and bone marrow precursors of these cell types.^[3]

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]

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.^[3]

References

↑ Dorgalaleh A.*, Naderi M, Hosseini MS, Alizadeh S, Hosseini S, Tabibian S, et al., (2015). "editors. Factor XIII Deficiency in Iran: A Comprehensive Review of the Literature. Seminars in thrombosis and hemostasis;" 41 (3 (41)): 323–329.
1 2 Laki K, Lóránd L (September 1948). "On the Solubility of Fibrin Clots". Science 108 (2802): 280. doi:10.1126/science.108.2802.280. PMID 17842715.
1 2 3 4 Muszbek L, Ariëns RA, Ichinose A (January 2007). "Factor XIII: recommended terms and abbreviations". J. Thromb. Haemost. 5 (1): 181–3. doi:10.1111/j.1538-7836.2006.02182.x. PMID 16938124.

External links

Proteins involved in coagulation

Coagulation factors

Primary hemostasis	vWF platelet membrane glycoproteins: Ib (A B IX) IIb/IIIa (IIb IIIa) VI

Intrinsic pathway	HMWK/Bradykinin Prekallikrein/Kallikrein XII "Hageman" XI IX VIII

Extrinsic pathway	III "Tissue factor" VII

Common pathway	X V II "(Pro)thrombin" I "Fibrin" Fibrinogen (FGA, FGG) XIII

Coagulation inhibitors

Thrombolysis/fibrinolysis

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 ATP citrate lyase HMG-CoA synthase Malate synthase

Enzymes

Activity	Active site Binding site Catalytic triad Oxyanion hole Enzyme promiscuity Catalytically perfect enzyme Coenzyme Cofactor Enzyme catalysis Enzyme kinetics Lineweaver–Burk plot Michaelis–Menten kinetics

Regulation	Allosteric regulation Cooperativity Enzyme inhibitor

Classification	EC number Enzyme superfamily Enzyme family List of enzymes

Types	EC1 Oxidoreductases(list) EC2 Transferases(list) EC3 Hydrolases(list) EC4 Lyases(list) EC5 Isomerases(list) EC6 Ligases(list)

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