Factor XI

Factor XI
Coagulation factor XI

PDB rendering based on 1xx9.
Symbols F11; FXI; MGC141891
External IDs OMIM264900 MGI99481 HomoloGene86654 GeneCards: F11 Gene
EC number
RNA expression pattern
PBB GE F11 206610 s at tn.png
More reference expression data
Species Human Mouse
Entrez 2160 109821
Ensembl ENSG00000088926 ENSMUSG00000031645
UniProt P03951 Q9DAT3
RefSeq (mRNA) NM_000128.3 NM_028066.1
RefSeq (protein) NP_000119.1 NP_082342.1
Location (UCSC) Chr 4:
187.19 – 187.21 Mb
Chr 8:
46.33 – 46.35 Mb
PubMed search [1] [2]

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]



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 μg/mL, corresponding to a plasma concentration (of FXI dimers) of approximately 30 nM. 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.


  1. ^ Fujikawa K, Chung DW, Hendrickson LE, Davie EW (May 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. 
  2. ^ a b Asakai R, Davie EW, Chung DW (November 1987). "Organization of the gene for human factor XI". Biochemistry 26 (23): 7221–8. doi:10.1021/bi00397a004. PMID 2827746. 
  3. ^ 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. 
  4. ^ Buetow KH, Shiang R, Yang P, Nakamura Y, Lathrop GM, White R, Wasmuth JJ, Wood S, Berdahl LD, Leysens NJ (May 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. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1683054. 
  5. ^ Wu W, Sinha D, Shikov S, Yip CK, Walz T, Billings PC, Lear JD, Walsh PN (July 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. PMC 2441546. PMID 18441012. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2441546. 
  6. ^ Walsh PN (July 2001). "Roles of platelets and factor XI in the initiation of blood coagulation by thrombin". Thromb. Haemost. 86 (1): 75–82. PMID 11487044. http://www.schattauer.de/index.php?id=1268&pii=th01070007&no_cache=1. 
  7. ^ Bolton-Maggs PH (June 1996). "Factor XI deficiency". Baillieres Clin. Haematol. 9 (2): 355–68. doi:10.1016/S0950-3536(96)80068-0. PMID 8800510. 

Further reading

External links

  • The MEROPS online database for peptidases and their inhibitors: S01.213

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