Factor XI

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Coagulation factor XI (plasma thromboplastin antecedent)
PBB Protein F11 image.jpg
PDB rendering based on 1xx9.
Identifiers
Symbol(s) F11; FXI; MGC141891
External IDs OMIM: 264900 MGI99481 Homologene86654
RNA expression pattern

PBB GE F11 206610 s at tn.png

More reference expression data

Orthologs
Human Mouse
Entrez 2160 109821
Ensembl ENSG00000088926 ENSMUSG00000031645
Uniprot P03951 Q9DAT3
Refseq NM_019559 (mRNA)
NP_062505 (protein)
NM_028066 (mRNA)
NP_082342 (protein)
Location Chr 4: 187.42 - 187.45 Mb Chr 8: 46.74 - 46.76 Mb
Pubmed search [1] [2]

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [3]


Overview

Factor XI or plasma thromboplastin antecedent is one of the enzymes of the coagulation cascade. Like many other coagulation factors, it is a serine protease.

Physiology

Factor XI (FXI) is produced by the liver and circulates as a homo-dimer in its inactive form. 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).

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 homo-dimer. 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.

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.

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

Further reading

  • Gailani D, Zivelin A, Sinha D, Walsh PN (2005). "Do platelets synthesize factor XI?". J. Thromb. Haemost. 2 (10): 1709–12. PMID 15456479. doi:10.1111/j.1538-7836.2004.00935.x. 
  • Dossenbach-Glaninger A, Hopmeier P (2005). "Coagulation factor XI: a database of mutations and polymorphisms associated with factor XI deficiency.". Blood Coagul. Fibrinolysis. 16 (4): 231–8. PMID 15870541. 
  • Seligsohn U (2007). "Factor XI in haemostasis and thrombosis: past, present and future.". Thromb. Haemost. 98 (1): 84–9. PMID 17597996. 
  • Meijers JC, Davie EW, Chung DW (1992). "Expression of human blood coagulation factor XI: characterization of the defect in factor XI type III deficiency.". Blood. 79 (6): 1435–40. PMID 1547342. 
  • Gailani D, Broze GJ (1991). "Factor XI activation in a revised model of blood coagulation.". Science. 253 (5022): 909–12. PMID 1652157. 
  • Buetow KH, Shiang R, Yang P; et al. (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. PMID 1673289. 
  • Bodfish P, Warne D, Watkins C; et al. (1992). "Dinucleotide repeat polymorphism in the human coagulation factor XI gene, intron B (F11), detected using the polymerase chain reaction.". Nucleic Acids Res. 19 (24): 6979. PMID 1762944. 
  • Clarkson K, Rosenfeld B, Fair J; et al. (1991). "Factor XI deficiency acquired by liver transplantation.". Ann. Intern. Med. 115 (11): 877–9. PMID 1952475. 
  • McMullen BA, Fujikawa K, Davie EW (1991). "Location of the disulfide bonds in human coagulation factor XI: the presence of tandem apple domains.". Biochemistry. 30 (8): 2056–60. PMID 1998667. 
  • Naito K, Fujikawa K (1991). "Activation of human blood coagulation factor XI independent of factor XII. Factor XI is activated by thrombin and factor XIa in the presence of negatively charged surfaces.". J. Biol. Chem. 266 (12): 7353–8. PMID 2019570. 
  • Asakai R, Chung DW, Davie EW, Seligsohn U (1991). "Factor XI deficiency in Ashkenazi Jews in Israel.". N. Engl. J. Med. 325 (3): 153–8. PMID 2052060. 
  • España F, Berrettini M, Griffin JH (1989). "Purification and characterization of plasma protein C inhibitor.". Thromb. Res. 55 (3): 369–84. PMID 2551064. 
  • Asakai R, Chung DW, Ratnoff OD, Davie EW (1989). "Factor XI (plasma thromboplastin antecedent) deficiency in Ashkenazi Jews is a bleeding disorder that can result from three types of point mutations.". Proc. Natl. Acad. Sci. U.S.A. 86 (20): 7667–71. PMID 2813350. 
  • Asakai R, Davie EW, Chung DW (1988). "Organization of the gene for human factor XI.". Biochemistry. 26 (23): 7221–8. PMID 2827746. 
  • 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. PMID 3636155. 
  • Warn-Cramer BJ, Bajaj SP (1986). "Stoichiometry of binding of high molecular weight kininogen to factor XI/XIa.". Biochem. Biophys. Res. Commun. 133 (2): 417–22. PMID 3936495. 
  • Bouma BN, Vlooswijk RA, Griffin JH (1983). "Immunologic studies of human coagulation factor XI and its complex with high molecular weight kininogen.". Blood. 62 (5): 1123–31. PMID 6626744. 
  • Tuszynski GP, Bevacqua SJ, Schmaier AH; et al. (1982). "Factor XI antigen and activity in human platelets.". Blood. 59 (6): 1148–56. PMID 7044446. 
  • Imanaka Y, Lal K, Nishimura T; et al. (1995). "Identification of two novel mutations in non-Jewish factor XI deficiency.". Br. J. Haematol. 90 (4): 916–20. PMID 7669672. 
  • Pugh RE, McVey JH, Tuddenham EG, Hancock JF (1995). "Six point mutations that cause factor XI deficiency.". Blood. 85 (6): 1509–16. PMID 7888672. 
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