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Factor XI

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Title: Factor XI  
Author: World Heritage Encyclopedia
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Subject: Coagulation, Factor IX, Factor XII, Thrombin, Haemophilia
Collection: Coagulation System, Ec 3.4.21, Zymogens
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Factor XI

Coagulation factor XI
PDB rendering based on 1xx9.
Available structures
PDB Ortholog search: PDBe, RCSB
Identifiers
Symbols  ; FXI
External IDs ChEMBL: GeneCards:
EC number
RNA expression pattern
Orthologs
Species Human Mouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)
RefSeq (protein)
Location (UCSC)
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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]

Contents

  • Function 1
  • Structure 2
  • Role in disease 3
  • See also 4
  • References 5
  • Further reading 6
  • External links 7

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.  
  2. ^ a b Asakai R, Davie EW, Chung DW (Nov 1987). "Organization of the gene for human factor XI". Biochemistry 26 (23): 7221–8.  
  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.  
  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". American Journal of Human Genetics 48 (5): 911–25.  
  5. ^ Wu W, Sinha D, Shikov S, Yip CK, Walz T, Billings PC, Lear JD, Walsh PN (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.  
  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.  
  7. ^ Bolton-Maggs PH (Jun 1996). "Factor XI deficiency". Baillière's Clinical Haematology 9 (2): 355–68.  

Further reading

  • Gailani D, Zivelin A, Sinha D, Walsh PN (Oct 2004). "Do platelets synthesize factor XI?". Journal of Thrombosis and Haemostasis : JTH 2 (10): 1709–12.  
  • Dossenbach-Glaninger A, Hopmeier P (Jun 2005). "Coagulation factor XI: a database of mutations and polymorphisms associated with factor XI deficiency". Blood Coagulation & Fibrinolysis : An International Journal in Haemostasis and Thrombosis 16 (4): 231–8.  
  • Seligsohn U (Jul 2007). "Factor XI in haemostasis and thrombosis: past, present and future". Thrombosis and Haemostasis 98 (1): 84–9.  
  • Meijers JC, Davie EW, Chung DW (Mar 1992). "Expression of human blood coagulation factor XI: characterization of the defect in factor XI type III deficiency". Blood 79 (6): 1435–40.  
  • Gailani D, Broze GJ (Aug 1991). "Factor XI activation in a revised model of blood coagulation". Science (New York, N.Y.) 253 (5022): 909–12.  
  • 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". American Journal of Human Genetics 48 (5): 911–25.  
  • Bodfish P, Warne D, Watkins C, Nyberg K, Spurr NK (Dec 1991). "Dinucleotide repeat polymorphism in the human coagulation factor XI gene, intron B (F11), detected using the polymerase chain reaction". Nucleic Acids Research 19 (24): 6979.  
  • Clarkson K, Rosenfeld B, Fair J, Klein A, Bell W (Dec 1991). "Factor XI deficiency acquired by liver transplantation". Annals of Internal Medicine 115 (11): 877–9.  
  • McMullen BA, Fujikawa K, Davie EW (Feb 1991). "Location of the disulfide bonds in human coagulation factor XI: the presence of tandem apple domains". Biochemistry 30 (8): 2056–60.  
  • Naito K, Fujikawa K (Apr 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". The Journal of Biological Chemistry 266 (12): 7353–8.  
  • Asakai R, Chung DW, Davie EW, Seligsohn U (Jul 1991). "Factor XI deficiency in Ashkenazi Jews in Israel". The New England Journal of Medicine 325 (3): 153–8.  
  • España F, Berrettini M, Griffin JH (Aug 1989). "Purification and characterization of plasma protein C inhibitor".  
  • Asakai R, Chung DW, Ratnoff OD, Davie EW (Oct 1989). "Factor XI (plasma thromboplastin antecedent) deficiency in Ashkenazi Jews is a bleeding disorder that can result from three types of point mutations". Proceedings of the National Academy of Sciences of the United States of America 86 (20): 7667–71.  
  • Asakai R, Davie EW, Chung DW (Nov 1987). "Organization of the gene for human factor XI". Biochemistry 26 (23): 7221–8.  
  • 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.  
  • Warn-Cramer BJ, Bajaj SP (Dec 1985). "Stoichiometry of binding of high molecular weight kininogen to factor XI/XIa". Biochemical and Biophysical Research Communications 133 (2): 417–22.  
  • Bouma BN, Vlooswijk RA, Griffin JH (Nov 1983). "Immunologic studies of human coagulation factor XI and its complex with high molecular weight kininogen". Blood 62 (5): 1123–31.  
  • Tuszynski GP, Bevacqua SJ, Schmaier AH, Colman RW, Walsh PN (Jun 1982). "Factor XI antigen and activity in human platelets". Blood 59 (6): 1148–56.  
  • Imanaka Y, Lal K, Nishimura T, Bolton-Maggs PH, Tuddenham EG, McVey JH (Aug 1995). "Identification of two novel mutations in non-Jewish factor XI deficiency". British Journal of Haematology 90 (4): 916–20.  
  • Pugh RE, McVey JH, Tuddenham EG, Hancock JF (Mar 1995). "Six point mutations that cause factor XI deficiency". Blood 85 (6): 1509–16.  
  • Riley PW, Cheng H, Samuel D, Roder H, Walsh PN (Mar 2007). "Dimer dissociation and unfolding mechanism of coagulation factor XI apple 4 domain: spectroscopic and mutational analysis". Journal of Molecular Biology 367 (2): 558–73.  
  • Samuel D, Cheng H, Riley PW, Canutescu AA, Nagaswami C, Weisel JW, Bu Z, Walsh PN, Roder H (Oct 2007). "Solution structure of the A4 domain of factor XI sheds light on the mechanism of zymogen activation". Proceedings of the National Academy of Sciences of the United States of America 104 (40): 15693–8.  

External links

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