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Open Access Articles- Top Results for Factor XI

Factor XI

Template:Infobox3cols/rowTemplate:Infobox3cols/rowTemplate:Infobox3cols/rowTemplate:Infobox3cols/rowTemplate:Infobox3cols/row
Identifiers
SymbolsF11 ; FXI
External IDsOMIM264900 MGI99481 HomoloGene86654 IUPHAR: 2360 ChEMBL: 2820 GeneCards: F11 Gene
EC number3.4.21.27
RNA expression pattern
File:PBB GE F11 206610 s at tn.png
More reference expression data
Orthologs
SpeciesHumanMouse
Entrez2160109821
EnsemblENSG00000088926ENSMUSG00000031645
UniProtP03951Q91Y47
RefSeq (mRNA)NM_000128NM_028066
RefSeq (protein)NP_000119NP_082342
Location (UCSC)Chr 4:
187.19 – 187.21 Mb
Chr 8:
45.24 – 45.26 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]

Function

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 FXIa itself; due to its activation by FXIIa, FXI is a member of the "contact pathway" (which 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).

Structure

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 hemophilia C; this mainly occurs in Ashkenazi Jews and is believed to affect approximately 8% of that population. Less commonly, hemophilia C can be found in Jews of Iraqi ancestry and in Israeli Arabs. 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.

See also

References

  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. PMID 3636155. doi:10.1021/bi00357a018. 
  2. ^ a b Asakai R, Davie EW, Chung DW (Nov 1987). "Organization of the gene for human factor XI". Biochemistry 26 (23): 7221–8. PMID 2827746. doi:10.1021/bi00397a004. 
  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". Cytogenetics and Cell Genetics 52 (1-2): 77–8. PMID 2612218. doi:10.1159/000132844. 
  4. ^ Buetow KH, Shiang R, Yang P, Nakamura Y, Lathrop GM, White R et al. (May 1991). "A detailed multipoint map of human chromosome 4 provides evidence for linkage heterogeneity and position-specific recombination rates". American Journal of Human Genetics 48 (5): 911–25. PMC 1683054. PMID 1673289. 
  5. ^ Wu W, Sinha D, Shikov S, Yip CK, Walz T, Billings PC et al. (Jul 2008). "Factor XI homodimer structure is essential for normal proteolytic activation by factor XIIa, thrombin, and factor XIa". The Journal of Biological Chemistry 283 (27): 18655–64. PMC 2441546. PMID 18441012. doi:10.1074/jbc.M802275200. 
  6. ^ Walsh PN (Jul 2001). "Roles of platelets and factor XI in the initiation of blood coagulation by thrombin". Thrombosis and Haemostasis 86 (1): 75–82. PMID 11487044. 
  7. ^ Bolton-Maggs PH (Jun 1996). "Factor XI deficiency". Baillière's Clinical Haematology 9 (2): 355–68. PMID 8800510. doi:10.1016/S0950-3536(96)80068-0. 

Further reading

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External links

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