Factor X
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2008-07-08T01:07:56Z
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'''Factor X''', also known by the [[eponym]] '''Stuart-Prower factor''' or as '''thrombokinase''', is an [[enzyme]] ({{EC number|3.4.21.6}}) of the [[coagulation|coagulation cascade]]. It is a [[serine protease|serine endopeptidase]] (protease group S1).
==Physiology==
Factor X is synthesized in the [[liver]] and requires [[vitamin K]] for its synthesis.
Factor X is activated into ''factor Xa'' by both [[factor IX]] (with its cofactor, [[factor VIII]] in a complex known as ''intrinsic Xase'') and [[factor VII]] with its cofactor, [[tissue factor]] (a complex known as ''extrinsic Xase''). It is therefore the first member of the ''final common pathway'' or ''thrombin pathway''.
It acts by cleaving [[prothrombin]] in two places (an [[arginine|arg]]-[[threonine|thr]] and then an [[arginine|arg]]-[[isoleucine|ile]] bond), which yields the active [[thrombin]]. This process is optimized when factor Xa is complexed with activated [[factor V|co-factor V]] in the [[prothrombinase]] complex.
Factor Xa is inactivated by [[protein Z-dependent protease inhibitor]] (ZPI), a [[serine protease inhibitor]] (serpin). The affinity of this protein for factor Xa is increased 1000-fold by the presence of [[protein Z]], while it does not require protein Z for inactivation of [[factor XI]]. Defects in protein Z lead to increased factor Xa activity and a propensity for thrombosis.
The half life of factor X is 40-45 hours.
==Genetics==
The human factor X [[gene]] is located on the thirteenth [[chromosome]] (13q34).
==Role in disease==
Inborn deficiency of factor X is very uncommon (1:500,000), and may present with [[epistaxis]] (nosebleeds), [[hemarthrosis]] (bleeding into joints) and gastrointestinal blood loss. Apart from congenital deficiency, low factor X levels may occur occasionally in a number of disease states.
Deficiency of vitamin K or antagonism by [[warfarin]] (or similar medication) leads to the production of an inactive factor X. In warfarin therapy, this is desirable to prevent [[thrombosis]]. As of late 2007, four out of five emerging [[Anticoagulant|anti-coagulation]] therapeutics targeted this enzyme.<ref name="WSJOct2007">{{cite news
| author = Ron Winslow | coauthors = Avery Johnson
| title = Race Is on for the Next Blood Thinner
| url = http://online.wsj.com/article/SB119725064671318856.html
| work = [[Wall Street Journal]] | page = A12 | date = 2007-12-10 | accessdate = 2008-01-06
| quote = The flurry of interest reflects increasing understanding of what doctors call the coagulation cascade... Four new blood thinners target an enzyme called factor Xa, one of several enzymes that play an important role in the cascade.
}}</ref>
==Therapeutic use==
Factor X is not commercially available as a concentrate, but is part of [[fresh frozen plasma]] and [[prothrombin complex]].
==Use in Biochemistry==
The Factor Xa protease can be used in biochemistry to cleave off protein tags that improve expression or purification of a protein of interest. Its preferred cleavage site (after the arginine in ile-glu/asp-gly-arg) can easily be engineered between a tag sequence and the protein of interest. After expression and purification, the tag is then proteolytically removed by Factor Xa.
==History==
American and British scientists described deficiency of factor X independently in 1953 and 1956, respectively. As with some other coagulation factors, the factor was initially named after these patients, a Mr Rufus Stuart and a Miss Audrey Prower.
==External links==
* {{eMedicine|med|3495}}
* [http://www.hemophilia.ca/en/2.3.6.php Factor X deficiency]
==References==
{{reflist}}
==Further reading==
{{refbegin | 2}}
{{PBB_Further_reading
| citations =
*{{cite journal | author=Cooper DN, Millar DS, Wacey A, ''et al.'' |title=Inherited factor X deficiency: molecular genetics and pathophysiology |journal=Thromb. Haemost. |volume=78 |issue= 1 |pages= 161–72 |year= 1997 |pmid= 9198147 |doi= }}
*{{cite journal | author=Hassan HJ, Leonardi A, Chelucci C, ''et al.'' |title=Blood coagulation factors in human embryonic-fetal development: preferential expression of the FVII/tissue factor pathway |journal=Blood |volume=76 |issue= 6 |pages= 1158–64 |year= 1990 |pmid= 1698100 |doi= }}
*{{cite journal | author=Messier TL, Pittman DD, Long GL, ''et al.'' |title=Cloning and expression in COS-1 cells of a full-length cDNA encoding human coagulation factor X |journal=Gene |volume=99 |issue= 2 |pages= 291–4 |year= 1991 |pmid= 1902434 |doi=10.1016/0378-1119(91)90141-W }}
*{{cite journal | author=Krishnaswamy S |title=Prothrombinase complex assembly. Contributions of protein-protein and protein-membrane interactions toward complex formation |journal=J. Biol. Chem. |volume=265 |issue= 7 |pages= 3708–18 |year= 1990 |pmid= 2303476 |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=Fung MR, Hay CW, MacGillivray RT |title=Characterization of an almost full-length cDNA coding for human blood coagulation factor X |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=82 |issue= 11 |pages= 3591–5 |year= 1985 |pmid= 2582420 |doi=10.1073/pnas.82.11.3591 }}
*{{cite journal | author=Jagadeeswaran P, Reddy SV, Rao KJ, ''et al.'' |title=Cloning and characterization of the 5' end (exon 1) of the gene encoding human factor X |journal=Gene |volume=84 |issue= 2 |pages= 517–9 |year= 1990 |pmid= 2612918 |doi=10.1016/0378-1119(89)90529-5 }}
*{{cite journal | author=Reddy SV, Zhou ZQ, Rao KJ, ''et al.'' |title=Molecular characterization of human factor XSan Antonio |journal=Blood |volume=74 |issue= 5 |pages= 1486–90 |year= 1989 |pmid= 2790181 |doi= }}
*{{cite journal | author=Kaul RK, Hildebrand B, Roberts S, Jagadeeswaran P |title=Isolation and characterization of human blood-coagulation factor X cDNA |journal=Gene |volume=41 |issue= 2-3 |pages= 311–4 |year= 1986 |pmid= 3011603 |doi=10.1016/0378-1119(86)90112-5 }}
*{{cite journal | author=Broze GJ, Warren LA, Novotny WF, ''et al.'' |title=The lipoprotein-associated coagulation inhibitor that inhibits the factor VII-tissue factor complex also inhibits factor Xa: insight into its possible mechanism of action |journal=Blood |volume=71 |issue= 2 |pages= 335–43 |year= 1988 |pmid= 3422166 |doi= }}
*{{cite journal | author=Gilgenkrantz S, Briquel ME, André E, ''et al.'' |title=Structural genes of coagulation factors VII and X located on 13q34 |journal=Ann. Genet. |volume=29 |issue= 1 |pages= 32–5 |year= 1986 |pmid= 3487272 |doi= }}
*{{cite journal | author=Leytus SP, Foster DC, Kurachi K, Davie EW |title=Gene for human factor X: a blood coagulation factor whose gene organization is essentially identical with that of factor IX and protein C |journal=Biochemistry |volume=25 |issue= 18 |pages= 5098–102 |year= 1986 |pmid= 3768336 |doi=10.1021/bi00366a018 }}
*{{cite journal | author=Leytus SP, Chung DW, Kisiel W, ''et al.'' |title=Characterization of a cDNA coding for human factor X |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=81 |issue= 12 |pages= 3699–702 |year= 1984 |pmid= 6587384 |doi=10.1073/pnas.81.12.3699 }}
*{{cite journal | author=McMullen BA, Fujikawa K, Kisiel W, ''et al.'' |title=Complete amino acid sequence of the light chain of human blood coagulation factor X: evidence for identification of residue 63 as beta-hydroxyaspartic acid |journal=Biochemistry |volume=22 |issue= 12 |pages= 2875–84 |year= 1983 |pmid= 6871167 |doi=10.1021/bi00281a016 }}
*{{cite journal | author=Marchetti G, Castaman G, Pinotti M, ''et al.'' |title=Molecular bases of CRM+ factor X deficiency: a frequent mutation (Ser334Pro) in the catalytic domain and a substitution (Glu102Lys) in the second EGF-like domain |journal=Br. J. Haematol. |volume=90 |issue= 4 |pages= 910–5 |year= 1995 |pmid= 7669671 |doi=10.1111/j.1365-2141.1995.tb05214.x }}
*{{cite journal | author=Morgenstern KA, Sprecher C, Holth L, ''et al.'' |title=Complementary DNA cloning and kinetic characterization of a novel intracellular serine proteinase inhibitor: mechanism of action with trypsin and factor Xa as model proteinases |journal=Biochemistry |volume=33 |issue= 11 |pages= 3432–41 |year= 1994 |pmid= 8136380 |doi=10.1021/bi00177a037 }}
*{{cite journal | author=Heeb MJ, Rosing J, Bakker HM, ''et al.'' |title=Protein S binds to and inhibits factor Xa |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=91 |issue= 7 |pages= 2728–32 |year= 1994 |pmid= 8146182 |doi=10.1073/pnas.91.7.2728 }}
*{{cite journal | author=Inoue K, Morita T |title=Identification of O-linked oligosaccharide chains in the activation peptides of blood coagulation factor X. The role of the carbohydrate moieties in the activation of factor X |journal=Eur. J. Biochem. |volume=218 |issue= 1 |pages= 153–63 |year= 1993 |pmid= 8243461 |doi=10.1111/j.1432-1033.1993.tb18361.x }}
*{{cite journal | author=Padmanabhan K, Padmanabhan KP, Tulinsky A, ''et al.'' |title=Structure of human des(1-45) factor Xa at 2.2 A resolution |journal=J. Mol. Biol. |volume=232 |issue= 3 |pages= 947–66 |year= 1993 |pmid= 8355279 |doi= 10.1006/jmbi.1993.1441 }}
*{{cite journal | author=Sinha U, Wolf DL |title=Carbohydrate residues modulate the activation of coagulation factor X |journal=J. Biol. Chem. |volume=268 |issue= 5 |pages= 3048–51 |year= 1993 |pmid= 8428982 |doi= }}
}}
{{refend}}
{{Coagulation}}
{{Serine endopeptidases}}
[[Category:EC 3.4.21]]
[[Category:Coagulation system]]
[[de:Stuart-Prower-Faktor]]
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