Factor XI
Template:PBB Factor XI or plasma thromboplastin antecedent is the zymogen form of factor XIa, one of the enzymes of the coagulation cascade. Like many other coagulation factors, it is a serine protease. In humans, Factor XI is encoded by the F11 gene.[1][2][3][4]
Physiology
Factor XI (FXI) is produced by the liver and circulates as a homo-dimer in its inactive form.[5] The plasma half-life of FXI is approximately 52 hours. The zymogen factor is activated into factor XIa by factor XIIa (FXIIa), thrombin, and it is also autocatalytic, and FXI is a member of the "contact pathway" due to activation by FXIIa (with includes HMWK, prekallikrein, factor XII, factor XI and factor IX).[6]
Factor XIa activates factor IX by selectively cleaving arg-ala and arg-val peptide bonds. Factor IXa, in turn, activates factor X.
Inhibitors of factor XIa include protein Z-dependent protease inhibitor (ZPI, a member of the serine protease inhibitor/serpin class of proteins), which is independent of protein Z (its action on factor X, however, is protein Z-dependent, hence its name).
Protein structure and molecular biology
Although synthesized as a single polypeptide chain, FXI circulates as a homodimer. Every chain has a relative molecular mass of approximately 80000. Typical plasma concentrations of FXI are 5 mg/l, corresponding to a plasma concentration (of FXI dimers) of approximately 30nM. The FXI gene is 23kb in length, has 15 exons, and is found on chromosome 4q32-35.[2][3]
Role in disease
Deficiency of factor XI causes the rare Haemophilia C; this mainly occurs in Ashkenazi Jews and is believed to affect approximately 8% of that population, of both sexes. The condition has been described in other populations at around 1% of cases. It is an autosomal recessive disorder. There is little spontaneous bleeding, but surgical procedures may cause excessive blood loss, and prophylaxis is required.[7]
Low levels of factor XI also occur in many other disease states, including Noonan syndrome.
High levels of factor XI have been implicated in thrombosis, although it is uncertain what determines these levels and how serious the procoagulant state is.
References
- ^ Fujikawa K, Chung DW, Hendrickson LE, Davie EW (1986). "Amino acid sequence of human factor XI, a blood coagulation factor with four tandem repeats that are highly homologous with plasma prekallikrein". Biochemistry. 25 (9): 2417–24. doi:10.1021/bi00357a018. PMID 3636155.
{{cite journal}}: Unknown parameter|month=ignored (help)CS1 maint: multiple names: authors list (link) - ^ a b Asakai R, Davie EW, Chung DW (1987). "Organization of the gene for human factor XI". Biochemistry. 26 (23): 7221–8. doi:10.1021/bi00397a004. PMID 2827746.
{{cite journal}}: Unknown parameter|month=ignored (help)CS1 maint: multiple names: authors list (link) - ^ a b Kato A, Asakai R, Davie EW, Aoki N (1989). "Factor XI gene (F11) is located on the distal end of the long arm of human chromosome 4". Cytogenet. Cell Genet. 52 (1–2): 77–8. doi:10.1159/000132844. PMID 2612218.
{{cite journal}}: CS1 maint: multiple names: authors list (link) - ^ Buetow KH, Shiang R, Yang P, Nakamura Y, Lathrop GM, White R, Wasmuth JJ, Wood S, Berdahl LD, Leysens NJ (1991). "A detailed multipoint map of human chromosome 4 provides evidence for linkage heterogeneity and position-specific recombination rates". Am. J. Hum. Genet. 48 (5): 911–25. PMC 1683054. PMID 1673289.
{{cite journal}}: Unknown parameter|month=ignored (help)CS1 maint: multiple names: authors list (link) - ^ Wu W, Sinha D, Shikov S, Yip CK, Walz T, Billings PC, Lear JD, Walsh PN (2008). "Factor XI homodimer structure is essential for normal proteolytic activation by factor XIIa, thrombin, and factor XIa". J. Biol. Chem. 283 (27): 18655–64. doi:10.1074/jbc.M802275200. PMID 18441012.
{{cite journal}}: Unknown parameter|month=ignored (help)CS1 maint: multiple names: authors list (link) CS1 maint: unflagged free DOI (link) - ^ Walsh PN (2001). "Roles of platelets and factor XI in the initiation of blood coagulation by thrombin". Thromb. Haemost. 86 (1): 75–82. PMID 11487044.
{{cite journal}}: Unknown parameter|month=ignored (help) - ^ Bolton-Maggs PH (1996). "Factor XI deficiency". Baillieres Clin. Haematol. 9 (2): 355–68. doi:10.1016/S0950-3536(96)80068-0. PMID 8800510.
{{cite journal}}: Unknown parameter|month=ignored (help)