Factor XIII (EC 2.3.2.13 ) is the last enzyme generated in the blood coagulation cascade. It is the zymogen for
fibrinoligase, a transglutaminase, which forms intramolecular gamma-glutamyl-epsilon-lysine crosslinking between
fibrin molecules. Crosslinking of fibrin stabilizes clot, as characterized by insolubility in 5M urea and 1%
monochloroacetic acid. Plasma factor XIII is composed of 2 A subunits, which have catalytic function, and 2 B subunits
. The B subunits of plasma factor XIII do not have transglutaminase activity and may serve as a carrier, since
platelet factor XIII is comprised simply of A2 dimers. Factor XIII is activated by the cleavage of a small peptide from
the A subunit by thrombin. The activated form is a transamidase.
NCBI Summary:
This gene encodes the coagulation factor XIII A subunit. Coagulation factor XIII is the last zymogen to become activated in the blood coagulation cascade. Plasma factor XIII is a heterotetramer composed of 2 A subunits and 2 B subunits. The A subunits have catalytic function, and the B subunits do not have enzymatic activity and may serve as plasma carrier molecules. Platelet factor XIII is comprised only of 2 A subunits, which are identical to those of plasma origin. Upon cleavage of the activation peptide by thrombin and in the presence of calcium ion, the plasma factor XIII dissociates its B subunits and yields the same active enzyme, factor XIIIa, as platelet factor XIII. This enzyme acts as a transglutaminase to catalyze the formation of gamma-glutamyl-epsilon-lysine crosslinking between fibrin molecules, thus stabilizing the fibrin clot. It also crosslinks alpha-2-plasmin inhibitor, or fibronectin, to the alpha chains of fibrin. Factor XIII deficiency is classified into two categories: type I deficiency, characterized by the lack of both the A and B subunits; and type II deficiency, characterized by the lack of the A subunit alone. These defects can result in a lifelong bleeding tendency, defective wound healing, and habitual abortion. [provided by RefSeq, Jul 2008]
General function
Enzyme, Ligase
Comment
Cellular localization
Secreted
Comment
candidate123
Ovarian function
Ovulation
Comment
Expression regulated by
Comment
Ovarian localization
Theca
Comment
Recheis B, et al 2000 reported that chicken coagulation factor XIIIA is produced by the theca externa and
stabilizes the ovarian follicular wall.
Differential mRNA display analysis of defined phases of chicken follicle development
resulted in the characterization of coagulation factor XIIIA. It is expressed and produced by cells
of the theca externa in a highly regulated manner during distinct growth phases of the follicle.
Transcripts for factor XIIIA are already detectable at the beginning of follicle development and
peak at the end of phase 2. Protein levels, however, still increase during phase 3, peak shortly
after ovulation, and persist until the postovulatory tissue is completely resorbed. Factor XIIIA is
secreted as a monomer into the extracellular matrix of the theca externa and is not associated
with factor XIIIB as is the case in plasma. Due to its transglutaminase
activity, factor XIIIA stabilizes the follicular wall by cross-linking matrix components. Thus,
coagulation factor XIIIA might play a key role in coping with the massive mechanical stress
exerted by the large amount of yolk accumulating during the rapid growth phase of the oocyte.
Follicle stages
Preovulatory
Comment
Phenotypes
PCO (polycystic ovarian syndrome)
Mutations
1 mutations
Species: human
Mutation name: None
type: None fertility: subfertile Comment: Androgen levels and metabolic parameters are associated with a genetic variant of F13A1 in women with polycystic ovary syndrome. Schweighofer N et al. The polycystic ovary syndrome (PCOS), characterized by hyperandrogenism, is one of the most common hormonal disorders among premenopausal women and is associated with infertility, obesity, and insulin resistance. Accumulating evidence suggests a role of the blood coagulation factor gene F13A1 in obesity (GeneBank ID: NM_000129.3). The aim of this study was to investigate the association of intronic allelic variants of the F13A1 gene with PCOS susceptibility and metabolic parameters in lean and obese PCOS women. In a case-control study, we determined an intronic F13A1 single nucleotide polymorphism (SNP) (dbSNP ID: rs7766109) in 585 PCOS and 171 control women and tested for PCOS susceptibility and associations with anthropometric, metabolic and hormonal parameters. Genotype frequencies of the F13A1 SNP rs7766109 were equivalent in PCOS and control women. In PCOS women, F13A1 gene variants were significantly associated with body mass index (BMI) (p=0.013), systolic blood pressure (p=0.042), insulin response (AUCins) (p=0.015), triglycerides (TG) (p=0.001), and high density lipoprotein cholesterol (HDL) (p=0.012). In the subgroup of obese PCOS women free androgen index (FAI), free testosterone and sex hormone binding globulin (SHBG) as well as glucose measurements showed a significantly different pattern across F13A1 gene variants (p=0.043; p=0.039 and p=0.013, respectively). We report for the first time an association of the F13A1 SNP rs7766109 with BMI, androgens, and insulin resistance in PCOS women. Further studies are needed to confirm our findings and to evaluate whether F13A1 is causally involved in the pathogenesis of PCOS related metabolic and hormonal disturbances.