Factor XI 1558491 224258758 2008-07-08T01:08:39Z ProteinBoxBot 3991663 Replaced protein Box Template with PBB Template for easy viewing. {{PBB|geneid=2160}} '''Factor XI''' or '''plasma thromboplastin antecedent''' is one of the [[enzyme]]s of the [[coagulation|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 XII]]a (FXIIa), [[thrombin]], and it is also [[autocatalytic]], and FXI is a member of the "contact pathway" due to activation by FXIIa (with includes [[high molecular weight kininogen|HMWK]], [[prekallikrein]], [[factor XII]], factor XI and [[factor IX]]). Factor XIa activates factor IX by selectively cleaving [[arginine|arg]]-[[alanine|ala]] and [[arginine|arg]]-[[valine|val]] [[peptide bond]]s. 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]] [[Jew]]s 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== {{reflist}} ==Further reading== {{refbegin | 2}} {{PBB_Further_reading | citations = *{{cite journal | author=Gailani D, Zivelin A, Sinha D, Walsh PN |title=Do platelets synthesize factor XI? |journal=J. Thromb. Haemost. |volume=2 |issue= 10 |pages= 1709–12 |year= 2005 |pmid= 15456479 |doi= 10.1111/j.1538-7836.2004.00935.x }} *{{cite journal | author=Dossenbach-Glaninger A, Hopmeier P |title=Coagulation factor XI: a database of mutations and polymorphisms associated with factor XI deficiency |journal=Blood Coagul. Fibrinolysis |volume=16 |issue= 4 |pages= 231–8 |year= 2005 |pmid= 15870541 |doi=10.1097/01.mbc.0000169214.62560.a5 }} *{{cite journal | author=Seligsohn U |title=Factor XI in haemostasis and thrombosis: past, present and future |journal=Thromb. Haemost. |volume=98 |issue= 1 |pages= 84–9 |year= 2007 |pmid= 17597996 |doi= }} *{{cite journal | author=Meijers JC, Davie EW, Chung DW |title=Expression of human blood coagulation factor XI: characterization of the defect in factor XI type III deficiency |journal=Blood |volume=79 |issue= 6 |pages= 1435–40 |year= 1992 |pmid= 1547342 |doi= }} *{{cite journal | author=Gailani D, Broze GJ |title=Factor XI activation in a revised model of blood coagulation |journal=Science |volume=253 |issue= 5022 |pages= 909–12 |year= 1991 |pmid= 1652157 |doi=10.1126/science.1652157 }} *{{cite journal | author=Buetow KH, Shiang R, Yang P, ''et al.'' |title=A detailed multipoint map of human chromosome 4 provides evidence for linkage heterogeneity and position-specific recombination rates |journal=Am. J. Hum. Genet. |volume=48 |issue= 5 |pages= 911–25 |year= 1991 |pmid= 1673289 |doi= }} *{{cite journal | author=Bodfish P, Warne D, Watkins C, ''et al.'' |title=Dinucleotide repeat polymorphism in the human coagulation factor XI gene, intron B (F11), detected using the polymerase chain reaction |journal=Nucleic Acids Res. |volume=19 |issue= 24 |pages= 6979 |year= 1992 |pmid= 1762944 |doi= }} *{{cite journal | author=Clarkson K, Rosenfeld B, Fair J, ''et al.'' |title=Factor XI deficiency acquired by liver transplantation |journal=Ann. Intern. Med. |volume=115 |issue= 11 |pages= 877–9 |year= 1991 |pmid= 1952475 |doi= }} *{{cite journal | author=McMullen BA, Fujikawa K, Davie EW |title=Location of the disulfide bonds in human coagulation factor XI: the presence of tandem apple domains |journal=Biochemistry |volume=30 |issue= 8 |pages= 2056–60 |year= 1991 |pmid= 1998667 |doi=10.1021/bi00222a008 }} *{{cite journal | author=Naito K, Fujikawa K |title=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 |journal=J. Biol. Chem. |volume=266 |issue= 12 |pages= 7353–8 |year= 1991 |pmid= 2019570 |doi= }} *{{cite journal | author=Asakai R, Chung DW, Davie EW, Seligsohn U |title=Factor XI deficiency in Ashkenazi Jews in Israel |journal=N. Engl. J. Med. |volume=325 |issue= 3 |pages= 153–8 |year= 1991 |pmid= 2052060 |doi= }} *{{cite journal | author=España F, Berrettini M, Griffin JH |title=Purification and characterization of plasma protein C inhibitor |journal=Thromb. Res. |volume=55 |issue= 3 |pages= 369–84 |year= 1989 |pmid= 2551064 |doi=10.1016/0049-3848(89)90069-8 }} *{{cite journal | author=Asakai R, Chung DW, Ratnoff OD, Davie EW |title=Factor XI (plasma thromboplastin antecedent) deficiency in Ashkenazi Jews is a bleeding disorder that can result from three types of point mutations |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=86 |issue= 20 |pages= 7667–71 |year= 1989 |pmid= 2813350 |doi=10.1073/pnas.86.20.7667 }} *{{cite journal | author=Asakai R, Davie EW, Chung DW |title=Organization of the gene for human factor XI |journal=Biochemistry |volume=26 |issue= 23 |pages= 7221–8 |year= 1988 |pmid= 2827746 |doi=10.1021/bi00397a004 }} *{{cite journal | author=Fujikawa K, Chung DW, Hendrickson LE, Davie EW |title=Amino acid sequence of human factor XI, a blood coagulation factor with four tandem repeats that are highly homologous with plasma prekallikrein |journal=Biochemistry |volume=25 |issue= 9 |pages= 2417–24 |year= 1986 |pmid= 3636155 |doi=10.1021/bi00357a018 }} *{{cite journal | author=Warn-Cramer BJ, Bajaj SP |title=Stoichiometry of binding of high molecular weight kininogen to factor XI/XIa |journal=Biochem. Biophys. Res. Commun. |volume=133 |issue= 2 |pages= 417–22 |year= 1986 |pmid= 3936495 |doi=10.1016/0006-291X(85)90922-2 }} *{{cite journal | author=Bouma BN, Vlooswijk RA, Griffin JH |title=Immunologic studies of human coagulation factor XI and its complex with high molecular weight kininogen |journal=Blood |volume=62 |issue= 5 |pages= 1123–31 |year= 1983 |pmid= 6626744 |doi= }} *{{cite journal | author=Tuszynski GP, Bevacqua SJ, Schmaier AH, ''et al.'' |title=Factor XI antigen and activity in human platelets |journal=Blood |volume=59 |issue= 6 |pages= 1148–56 |year= 1982 |pmid= 7044446 |doi= }} *{{cite journal | author=Imanaka Y, Lal K, Nishimura T, ''et al.'' |title=Identification of two novel mutations in non-Jewish factor XI deficiency |journal=Br. J. Haematol. |volume=90 |issue= 4 |pages= 916–20 |year= 1995 |pmid= 7669672 |doi=10.1111/j.1365-2141.1995.tb05215.x }} *{{cite journal | author=Pugh RE, McVey JH, Tuddenham EG, Hancock JF |title=Six point mutations that cause factor XI deficiency |journal=Blood |volume=85 |issue= 6 |pages= 1509–16 |year= 1995 |pmid= 7888672 |doi= }} }} {{refend}} {{Coagulation}} {{Serine endopeptidases}} [[Category:EC 3.4.21]] [[Category:Coagulation system]] [[Category:Genes associated with genetic disorders]] [[de:Plasma thromboplastin antecedent]] <!-- The PBB_Controls template provides controls for Protein Box Bot, please see Template:PBB_Controls for details. --> {{PBB_Controls | update_page = yes | require_manual_inspection = no | update_protein_box = yes | update_summary = no | update_citations = yes }}