Factor XI
| Coagulation factor XI |
PDB rendering based on 1xx9. |
| Available structures |
| PDB |
1XX9, 1XXD, 1XXF, 1ZHM, 1ZHP, 1ZHR, 1ZJD, 1ZLR, 1ZMJ, 1ZML, 1ZMN, 1ZOM, 1ZPB, 1ZPC, 1ZPZ, 1ZRK, 1ZSJ, 1ZSK, 1ZSL, 1ZTJ, 1ZTK, 1ZTL, 2F83, 2FDA, 2J8J, 2J8L, 3BG8 |
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| Identifiers |
| Symbols |
F11; FXI; MGC141891 |
| External IDs |
OMIM: 264900 MGI: 99481 HomoloGene: 86654 GeneCards: F11 Gene |
| EC number |
3.4.21.27 |
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| RNA expression pattern |
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| More reference expression data |
| Orthologs |
| Species |
Human |
Mouse |
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| Entrez |
2160 |
109821 |
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| Ensembl |
ENSG00000088926 |
ENSMUSG00000031645 |
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| UniProt |
P03951 |
Q9DAT3 |
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| RefSeq (mRNA) |
NM_000128.3 |
NM_028066.1 |
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| RefSeq (protein) |
NP_000119.1 |
NP_082342.1 |
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| Location (UCSC) |
Chr 4:
187.19 – 187.21 Mb |
Chr 8:
46.33 – 46.35 Mb |
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| PubMed search |
[1] |
[2] |
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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]
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 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.
References
- ^ 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.
- ^ 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.
- ^ 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.
- ^ 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.
- ^ 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.
- ^ 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.
- ^ 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
- Gailani D, Zivelin A, Sinha D, Walsh PN (2005). "Do platelets synthesize factor XI?". J. Thromb. Haemost. 2 (10): 1709–12. doi:10.1111/j.1538-7836.2004.00935.x. PMID 15456479.
- 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. doi:10.1097/01.mbc.0000169214.62560.a5. 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. doi:10.1126/science.1652157. 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. PMC 1683054. PMID 1673289. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1683054.
- 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. doi:10.1093/nar/19.24.6979-a. PMC 329377. PMID 1762944. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=329377.
- 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. doi:10.1021/bi00222a008. 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. doi:10.1056/NEJM199107183250303. PMID 2052060.
- España F, Berrettini M, Griffin JH (1989). "Purification and characterization of plasma protein C inhibitor". Thromb. Res. 55 (3): 369–84. doi:10.1016/0049-3848(89)90069-8. 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. doi:10.1073/pnas.86.20.7667. PMC 298131. PMID 2813350. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=298131.
- Asakai R, Davie EW, Chung DW (1988). "Organization of the gene for human factor XI". Biochemistry 26 (23): 7221–8. doi:10.1021/bi00397a004. 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. doi:10.1021/bi00357a018. 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. doi:10.1016/0006-291X(85)90922-2. 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. doi:10.1111/j.1365-2141.1995.tb05215.x. 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.
- Riley PW, Cheng H, Samuel D, Roder H, Walsh PN (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. doi:10.1016/j.jmb.2006.12.066. PMC 1945241. PMID 17257616. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1945241.
- Samuel D, Cheng H, Riley PW, Canutescu AA, Nagaswami C, Weisel JW, Bu Z, Walsh PN, Roder H (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 USA 104 (40): 15693–8. doi:10.1073/pnas.0703080104. PMC 1987390. PMID 17884987. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1987390.
External links
- The MEROPS online database for peptidases and their inhibitors: S01.213
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PDB gallery
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1xx9: Crystal Structure of the FXIa Catalytic Domain in Complex with EcotinM84R
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1xxd: Crystal Structure of the FXIa Catalytic Domain in Complex with mutated Ecotin
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1xxf: Crystal Structure of the FXIa Catalytic Domain in Complex with Ecotin Mutant (EcotinP)
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1zhm: Crystal Structure of the Catalytic Domain of the Coagulation Factor XIa in Complex with Benzamidine (S434A-T475A-K437 Mutant)
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1zhp: Crystal Structure of the Catalytic Domain of Coagulation Factor XI in Complex with Benzamidine (S434A-T475A-K505 Mutant)
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1zhr: Crystal Structure of the Catalytic Domain of Coagulation Factor XI in Complex with Benzamidine (S434A-T475A-C482S-K437A Mutant)
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1zjd: Crystal Structure of the Catalytic Domain of Coagulation Factor XI in Complex with Kunitz Protease Inhibitor Domain of Protease Nexin II
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1zlr: Factor XI catalytic domain complexed with 2-guanidino-1-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)ethyl nicotinate
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1zmj: Crystal Structure of the Catalytic Domain of Factor XI in complex with 4-(guanidinomethyl)-phenylboronic acid
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1zml: Crystal Structure of the Catalytic Domain of Factor XI in complex with (R)-1-(4-(4-(hydroxymethyl)-1,3,2-dioxaborolan-2-yl)phenethyl)guanidine
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1zmn: Crystal Structure of the Catalytic Domain of Coagulation Factor XI in Complex with (R)-1-(4-(4-(hydroxymethyl)-1,3,2-dioxaborolan-2-yl)phenyl)guanidine
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1zom: Crystal Structure of the Catalytic Domain of Coagulation Factor XI in complex with a peptidomimetic Inhibitor
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1zpb: Crystal Structure of the Catalytic Domain of Coagulation Factor XI in Complex with 4-Methyl-pentanoic acid {1-[4-guanidino-1-(thiazole-2-carbonyl)-butylcarbamoyl]-2-methyl-propyl}-amide
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1zpc: Crystal Structure of the Catalytic Domain of Coagulation Factor XI in Complex with 2-[2-(3-Chloro-phenyl)-2-hydroxy-acetylamino]-N-[4-guanidino-1-(thiazole-2-carbonyl)-butyl]-3-methyl-butyramide
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1zpz: Factor XI catalytic domain complexed with N-((R)-1-(4-bromophenyl)ethyl)urea-Asn-Val-Arg-alpha-ketothiazole
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1zrk: Factor XI complexed with 3-hydroxypropyl 3-(7-amidinonaphthalene-1-carboxamido)benzenesulfonate
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1zsj: Crystal Structure of the Catalytic Domain of Coagulation Factor XI in complex with N-(7-Carbamimidoyl-naphthalen-1-yl)-3-hydroxy-2-methyl-benzamide
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1zsk: Crystal Structure of the Catalytic Domain of Coagulation Factor XI in Complex with 6-Carbamimidoyl-4-(3-hydroxy-2-methyl-benzoylamino)-naphthalene-2-carboxylic acid methyl ester
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1zsl: Factor XI complexed with a pyrimidinone inhibitor
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1ztj: Crystal Structure of the Catalytic Domain of Coagulation Factor XI in Complex with 2-(5-Benzylamino-2-methylsulfanyl-6-oxo-6H-pyrimidin-1-yl)-N-[4-guanidino-1-(thiazole-2-carbonyl)-butyl]-acetamide
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1ztk: Crystal Structure of the Catalytic Domain of Coagulation Factor XI in Complex with 2-(5-Amino-6-oxo-2-m-tolyl-6H-pyrimidin-1-yl)-N-[4-guanidino-1-(thiazole-2-carbonyl)-butyl]-acetamide
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1ztl: Crystal Structure of the Catalytic Domain of Coagulation Factor XI in Complex with N-[4-Guanidino-1-(thiazole-2-carbonyl)-butyl]-2-{6-oxo-5-[(quinolin-8-ylmethyl)-amino]-2-m-tolyl-6H-pyrimidin-1-yl}-acetamide
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2f83: Crystal structure at 2.9 Angstroms resolution of human plasma coagulation factor XI zymogen
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2fda: Crystal Structure of the Catalytic Domain of Human Coagulation Factor XIa in Complex with alpha-Ketothiazole Arginine Derived Ligand
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| Digestive enzymes |
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| Coagulation |
factors: Thrombin · Factor VIIa · Factor IXa · Factor Xa · Factor XIa · Factor XIIa · Kallikrein ( PSA, KLK1, KLK2, KLK3, KLK4, KLK5, KLK6, KLK7, KLK8, KLK9, KLK10, KLK11, KLK12, KLK13, KLK14, KLK15)
fibrinolysis: Plasmin · Plasminogen activator ( Tissue plasminogen activator · Urinary plasminogen activator)
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| Complement system |
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| Other immune system |
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| Venombin |
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B enzm: 1.1/2/3/4/5/6/7/8/10/11/13/14/15-18, 2.1/2/3/4/5/6/7/8, 2.7.10, 2.7.11-12, 3.1/2/3/4/5/6/7, 3.1.3.48, 3.4.21/22/23/24, 4.1/2/3/4/5/6, 5.1/2/3/4/99, 6.1-3/4/5-6
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