Factor XIII

Class of enzymes

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. 6 p24.2-p23
| Search for

Structures| Swiss-model
Domains| InterPro
coagulation factor XIII,
B polypeptide

Identifiers
Symbol| F13B
NCBI gene| 2165
HGNC| 3534
OMIM| 134580
RefSeq| NM_001994
UniProt| P05160
Other data
Locus| Chr. 1 q31-q32.1
| Search for

Structures| Swiss-model
Domains| InterPro

Factor XIII, or fibrin stabilizing factor, is a plasma protein and zymogen. It is activated by thrombin to factor XIIIa which crosslinks fibrin in coagulation. Deficiency of XIII worsens clot stability and increases bleeding tendency.[1]

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.[1]

## Function

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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.[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, plasmin, antithrombin and TFPI 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)

## Genetics

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Human factor XIII consist of A and B subunits. A subunit gene is F13A1. It is on 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]

* 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 kbp, 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

[edit]

Factor XIII of human blood is a heterotetramer of two A and two B linear polypeptides or "units". A units are potentially catalytic; B units are not. A units form a dimeric 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 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 kDa, 731 amino acid residues, 5 protein domains (listed from the N-terminal to 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 W279 partake in catalysis
* β-barrel 1 (516–628)
* β-barrel 2 (629–731)

B units are glycoproteins. Each has a mass of about 80 kDa (8.5% of the mass is from carbohydrates), 641 residues and 10 sushi domains. Each domain has about 60 residues and 2 internal disulfide bonds.[1]

## Physiology

[edit]

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

[edit]

Factor XIII deficiency, 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.[3]

## Diagnostic use

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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

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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]

## See also

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

## References

[edit]

1. ^ a b c d e f g h i j k l Muszbek L, Bereczky Z, Bagoly Z, Komáromi I, Katona É (July 2011). "Factor XIII: a coagulation factor with multiple plasmatic and cellular functions". Physiological Reviews. 91 (3): 931–72\. doi:10.1152/physrev.00016.2010. PMID 21742792. S2CID 24703788.
2. ^ a b Laki K, Lóránd L (September 1948). "On the Solubility of Fibrin Clots". Science. 108 (2802): 280. Bibcode:1948Sci...108..280L. doi:10.1126/science.108.2802.280. 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)
4. ^ a b Muszbek L, Ariëns RA, Ichinose A (January 2007). "Factor XIII: recommended terms and abbreviations". Journal of Thrombosis and Haemostasis. 5 (1): 181–83\. doi:10.1111/j.1538-7836.2006.02182.x. PMID 16938124. S2CID 20424049.

## External links

[edit]

* Factor XIII deficiency at hemophilia.org
* med/3491 at eMedicine

* v
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Coagulation cascade

Coagulation factors|

| Primary hemostasis
(platelet activation)|

* von Willebrand factor (vWF)
* Platelet membrane glycoproteins: Glycoprotein Ib (GPIb) (GP1BA
* GP1BB
* Glycoprotein IX (GP9))
* Glycoprotein IIb/IIIa (GPIIb
* GPIIIa)
* Glycoprotein VI (GPVI)

|

Intrinsic pathway
(contact activation)|

* High-molecular-weight kininogen (HMWK)
* Bradykinin
* Prekallikrein
* Kallikrein
* Factor XII (Hageman factor)
* Factor XI
* Factor IX
* Factor VIII

Extrinsic pathway
(tissue factor)|

* Factor III (tissue factor)
* Factor VII

Common pathway|

* Factor X
* Factor V
* Prothrombin (factor II)
* Thrombin (factor IIa)
* Fibrinogen (factor I) (FGA, FGG)
* Fibrin (factor Ia)
* Factor XIII

Anticoagulant factors|

* Antithrombin (inhibits FII, FIX, FX, FXI, FXII)
* Protein C (inhibits FV, FVIII)
* Protein S (cofactor for protein C)
* Protein Z (inhibits FX)
* Protein Z-related protease inhibitor (ZPI) (inhibits FX, FXI)
* Tissue factor pathway inhibitor (TFPI) (inhibits FIII)

Fibrinolytic factors|

* Plasminogen
* Plasmin
* Tissue plasminogen activator (tPA)
* Urokinase
* Plasminogen activator inhibitor-1 (PAI-1)
* Plasminogen activator inhibitor-2 (PAI-2)
* α2-Antiplasmin
* α2-Macroglobulin
* Thrombin-activatable fibrinolysis inhibitor (TAFI)

Coagulation markers|

| Platelet activation|

* Platelet factor 4 (PF4)
* β-Thromboglobulin (β-TG)

|

Thrombin generation|

* Prothrombin fragment 1+2 (F1+2)
* Thrombin–antithrombin complex (TAT)
* Activated protein C–protein C inhibitor (APC–PCI)

Fibrin generation|

* Fibrinopeptide A (FpA)
* Fibrinopeptide B (FpB)
* Fibrin monomers (FM)

Fibrinolysis|

* Plasmin-α2-antiplasmin complex (PAP)
* D-Dimer (DD)

* 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)

Portal:

* Biology

Authority control databases

National|

* United States
* Israel

Other|

* Yale LUX

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