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[[Image:Factor XIII.png|right|thumb|250px|Factor XIII crosslinks fibrin]]
[[Image:Stabilisation de la fibrine par le factor XIII.png|right|thumb|260px|Factor XIII crosslinks fibrin]]
{{protein
{{infobox protein
| Name = coagulation factor XIII, A1 polypeptide
| Name = [[F13A1|coagulation factor XIII,<br />A1 polypeptide]]
| caption =  
| caption =  
| image =  
| image =  
| width =  
| width =  
| HGNCid = 3531
| HGNCid = 3531
| Symbol = F13A1
| Symbol = [[F13A1]]
| AltSymbols = F13A
| AltSymbols = F13A
| EntrezGene = 2162
| EntrezGene = 2162
Line 19: Line 19:
| LocusSupplementaryData = .2-p23
| LocusSupplementaryData = .2-p23
}}
}}
{{protein
{{infobox protein
| Name = coagulation factor XIII, B polypeptide
| Name = [[F13B|coagulation factor XIII,<br />B polypeptide]]
| caption =  
| caption =  
| image =  
| image =  
| width =  
| width =  
| HGNCid = 3534
| HGNCid = 3534
| Symbol = F13B
| Symbol = [[F13B]]
| AltSymbols =  
| AltSymbols =  
| EntrezGene = 2165
| EntrezGene = 2165
Line 38: Line 38:
| LocusSupplementaryData = -q32.1
| LocusSupplementaryData = -q32.1
}}
}}
{{SI}}
'''Factor XIII''' or '''fibrin stabilizing factor''' is an [[enzyme]] ({{EC number|2.3.2.13}}) of the [[coagulation|blood coagulation system]] that crosslinks [[fibrin]]. Deficiency of this factor (FXIIID) affects clot stability. FXIIID, while generally rare, does occur, with Iran having the highest global incidence of the disorder with 473 cases. The city of [[Khash, Iran|Khash]], located in [[Sistan]] and [[Balochistan]] provinces, has the highest incidence in Iran, with a high rate of consanguineous marriage.<ref>{{cite journal | vauthors =  Dorgalaleh A, Naderi M, Hosseini MS, Alizadeh S, Hosseini S, Tabibian S |display-authors=etal | title = Factor XIII Deficiency in Iran: A Comprehensive Review of the Literature. Seminars in thrombosis and hemostasis;  |  volume = 41  | issue =  3 (41) | pages = 323–329 | date=2015}}</ref>
{{CMG}}


== 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.


==Overview==
Factor XIII is activated by thrombin into factor XIIIa; its activation into Factor XIIIa requires [[calcium in biology|calcium]] as a [[Cofactor (biochemistry)|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.  
'''Factor XIII''' or '''fibrin stabilizing factor''' is an [[enzyme]] ({{EC number|2.3.2.13}}) of the [[coagulation|blood coagulation system]] that crosslinks [[fibrin]]. 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 in biology|calcium]] as a [[Cofactor (biochemistry)|cofactor]].


FXIII is known also as Laki-Lorand factor, after the scientists who first proposed its existence in 1948.<ref name=Laki>Laki K, Lorand L. On the solubility of fibrin clots. ''Science'' 1948;108:280.</ref> A 2005 conference recommended standardization of nomenclature.<ref name=Muszbek>{{cite journal | author = | title = Factor XIII: recommended terms and abbreviations. | journal = J Thromb Haemost | volume = | issue = | pages = | year = | id = PMID 16938124}}</ref>
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]].{{citation needed|date=November 2012}}


==Genetics==
== Discovery ==
Zymogene factor XIII is a 320000 M<sub>r</sub> glycoprotein tetramer consisting of twice two subunits (2 A and 2 B),<ref name=Muszbek/> the [[gene]]s for which are on different [[chromosome]]s:
FXIII is also known as Laki–Lorand factor, after [[Kalman Laki]] and [[Laszlo Lorand]], the scientists who first proposed its existence in 1948.<ref name="Laki">{{cite journal |vauthors=Laki K, Lóránd L | title = On the Solubility of Fibrin Clots | journal = Science | volume = 108 | issue = 2802 | pages = 280 |date=September 1948 | pmid = 17842715 | doi = 10.1126/science.108.2802.280 | url = }}</ref> A 2005 conference recommended standardization of nomenclature.<ref name="Muszbek">{{cite journal |vauthors=Muszbek L, Ariëns RA, Ichinose A | title = Factor XIII: recommended terms and abbreviations | journal = J. Thromb. Haemost. | volume = 5 | issue = 1 | pages = 181–83 |date=January 2007 | pmid = 16938124 | doi = 10.1111/j.1538-7836.2006.02182.x | url = }}</ref>
* 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 83000.
* 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 76500.


==Physiology==
== Genetics ==
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 5-9 days. It is present in plasma, [[platelet]]s, and [[monocyte]]s, as well as [[macrophage]]s and bone marrow precursors of these cell types.<ref name=Muszbek/>


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.<ref name=Laki/>
[[Zymogen]] factor XIII is a 320kDa glycoprotein tetramer consisting of two twin subunits (2 A and 2 B),<ref name=Muszbek/> the [[gene]]s for which are on different [[chromosome]]s:
* [[F13A1|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.
* [[F13B|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.
 
==Structure==
Factor XIII has two forms: a plasmatic form that flows freely in the [[blood plasma]], and [[Coagulation factor XIII, A1 polypeptide|a cellular form]] carried inside [[platelet alpha-granule]]s.
 
The cellular form is a dimer of two identical subunits, FXIII-A, each consisting of an activation peptide that is cleaved upon activation, a [[β-sandwich]] domain, a catalytic [[transglutaminase]] domain and two [[β-barrel]] domains.
 
The plasmatic form includes two additional identical subunits, FXIII-B, that is released in a [[calcium]]-dependent manner upon activation peptide cleavage. Each FXIII-B is both inhibitory and serves as a plasma carrier, and consists of ten repetitive [[sushi domain]]s held together by two internal [[disulfide bond]] each. During circulation, this subunit binds fibrinogen.
<ref>{{cite journal |vauthors=Komáromi I, Bagoly Z, Muszbek L | title = Factor XIII: novel structural and functional aspects | journal = Journal of Thrombosis and Haemostasis | volume = 9 | issue = 1 | pages = 9–20 |date=Jan 2011 | pmid = 20880254 | doi = 10.1111/j.1538-7836.2010.04070.x }}</ref>
 
== 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, [[platelet]]s, and [[monocyte]]s, as well as [[macrophage]]s and bone marrow precursors of these cell types.<ref name=Muszbek/>
 
A clot that has not been stabilized by FXIIIa is soluble in 5&nbsp;mol/L [[urea]], while a stabilized clot is resistant to this phenomenon.<ref name=Laki/>
 
== Diagnostic use ==


==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.<ref name=Muszbek/>
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.<ref name=Muszbek/>


==See also==
== See also ==
* [[Factor XIII deficiency]]
* [[Factor XIII deficiency]]
* [[D-dimer]]
* [[D-dimer]]
* [[Coagulation]]


==References==
==References==
{{reflist|2}}
{{Reflist}}
 
== External links ==
* [http://www.hemophilia.org/bdi/bdi_types11.htm Factor XIII deficiency at hemophilia.org]
* {{eMedicine|med|3491}}


{{Coagulation}}
{{Coagulation}}
{{Acyltransferases}}
{{Acyltransferases}}
 
{{Enzymes}}
{{Portal bar|Molecular and Cellular Biology|border=no}}


[[Category:Coagulation system]]
[[Category:Coagulation system]]
[[Category:EC 2.3.2]]
[[Category:EC 2.3.2]]
 
[[Category:Zymogens]]
[[fr:Facteur Laki-Lorand]]
 
[[Category:Hematology]]
[[Category:Mature chapter]]
 
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Latest revision as of 19:38, 3 January 2019

File:Stabilisation de la fibrine par le factor XIII.png
Factor XIII crosslinks fibrin
coagulation factor XIII,
A1 polypeptide
Identifiers
SymbolF13A1
Alt. symbolsF13A
Entrez2162
HUGO3531
OMIM134570
RefSeqNM_000129
UniProtP00488
Other data
LocusChr. 6 p24.2-p23
coagulation factor XIII,
B polypeptide
Identifiers
SymbolF13B
Entrez2165
HUGO3534
OMIM134580
RefSeqNM_001994
UniProtP05160
Other data
LocusChr. 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, does occur, with Iran having the highest global incidence of the disorder with 473 cases. The city of Khash, located in Sistan and Balochistan provinces, has the highest incidence in Iran, with a 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.[citation needed]

Discovery

FXIII 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.[3]

Genetics

Zymogen factor XIII is a 320kDa glycoprotein tetramer consisting of two twin 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.

Structure

Factor XIII has two forms: a plasmatic form that flows freely in the blood plasma, and a cellular form carried inside platelet alpha-granules.

The cellular form is a dimer of two identical subunits, FXIII-A, each consisting of an activation peptide that is cleaved upon activation, a β-sandwich domain, a catalytic transglutaminase domain and two β-barrel domains.

The plasmatic form includes two additional identical subunits, FXIII-B, that is released in a calcium-dependent manner upon activation peptide cleavage. Each FXIII-B is both inhibitory and serves as a plasma carrier, and consists of ten repetitive sushi domains held together by two internal disulfide bond each. During circulation, this subunit binds fibrinogen. [4]

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]

See also

References

  1. ↑ 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 (41)): 323–329.
  2. ↑ 2.0 2.1 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.
  3. ↑ 3.0 3.1 3.2 3.3 Muszbek L, Ariëns RA, Ichinose A (January 2007). "Factor XIII: recommended terms and abbreviations". J. Thromb. Haemost. 5 (1): 181–83. doi:10.1111/j.1538-7836.2006.02182.x. PMID 16938124.
  4. ↑ Komáromi I, Bagoly Z, Muszbek L (Jan 2011). "Factor XIII: novel structural and functional aspects". Journal of Thrombosis and Haemostasis. 9 (1): 9–20. doi:10.1111/j.1538-7836.2010.04070.x. PMID 20880254.

External links

Retrieved from "https://www.wikidoc.org/index.php?title=Factor_XIII&oldid=1536337"