View source for Factor X

{{cs1 config|name-list-style=vanc|display-authors=6}}
{{Short description|Mammalian protein found in Homo sapiens}}
{{Other uses}}
{{Infobox_gene}}

'''Coagulation factor X''' ({{EC number|3.4.21.6}}),  or '''Stuart factor''', is an [[enzyme]] of the [[coagulation cascade]], encoded in humans by ''F10'' gene.<ref name="Medline2024">{{cite web |title=F10 gene: MedlinePlus Genetics |url=https://medlineplus.gov/genetics/gene/f10/ |website=medlineplus.gov |language=en}}</ref> It is a [[serine endopeptidase]] (protease group S1, [[PA clan]]). Factor X is synthesized in the [[liver]] and requires [[vitamin K]] for its synthesis.

Factor X is activated, by hydrolysis, into '''factor Xa''' by both [[factor IX]] with its cofactor, [[factor VIII]] in a complex known as [[Tenase|intrinsic pathway]]; and [[factor VII]] with its cofactor, [[tissue factor]] in a complex known as [[Tenase|extrinsic pathway]].<ref name="Camire">{{cite journal | vauthors = Camire RM | title = Blood coagulation factor X: molecular biology, inherited disease, and engineered therapeutics | journal = Journal of Thrombosis and Thrombolysis | volume = 52 | issue = 2 | pages = 383–390 | date = August 2021 | pmid = 33886037 | pmc = 8531165 | doi = 10.1007/s11239-021-02456-w }}</ref> 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.

== Structure ==
{{See also|Factor IX#Domain architecture}}
The first crystal structure of human factor Xa was deposited in May 1993. To date, 191 crystal structures of factor Xa with various inhibitors have been deposited in the protein data bank. The active site of factor Xa is divided into four subpockets as S1, S2, S3 and S4. The S1 subpocket determines the major component of selectivity and binding. The S2 sub-pocket is small, shallow and not well defined. It merges with the S4 subpocket. The S3 sub-pocket is located on the rim of the S1 pocket and is quite exposed to solvent. The S4 sub-pocket has three ligand binding domains: the "hydrophobic box", the "cationic hole" and the water site. Factor Xa inhibitors generally bind in an L-shaped conformation, where one group of the ligand occupies the anionic S1 pocket lined by residues [[Aspartic acid|Asp]]189, [[Serine|Ser]]195, and [[Tyrosine|Tyr]]228, and another group of the ligand occupies the aromatic S4 pocket lined by residues Tyr99, [[Phenylalanine|Phe]]174, and Trp215. Typically, a fairly rigid linker group bridges these two interaction sites.<ref>{{Cite web |url=http://pharmaxchange.info/presentations/Direct%20FXa%20Inhibitors.html |title=Presentation on Direct Factor Xa Inhibitors |access-date=2010-04-08 |archive-url=https://web.archive.org/web/20160303184211/http://pharmaxchange.info/presentations/Direct%20FXa%20Inhibitors.html |archive-date=2016-03-03 |url-status=dead }}</ref>

==Genetics==
The human factor X [[gene]] is located on [[chromosome 13]] (13q34).

==Role in disease==
{{main|Factor X deficiency}}
Inborn deficiency of factor X is very rare (1:1,000,000), 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.  For example, factor X deficiency may be seen in [[amyloidosis]], where factor X is adsorbed to the amyloid fibrils in the vasculature.

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 | author2 = Avery Johnson | title = Race Is on for the Next Blood Thinner | url = https://www.wsj.com/articles/SB119725064671318856 | work =[[The Wall Street Journal]] | page = A12 | date = 2007-12-10 | access-date = 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. | archive-url = https://web.archive.org/web/20160310111746/http://www.wsj.com/articles/SB119725064671318856 | archive-date = 2016-03-10 | url-status = live }}</ref>

Inhibiting Factor Xa would offer an alternate method for anticoagulation. [[Direct Xa inhibitor]]s are popular anticoagulants.

Polymorphisms in Factor X have been associated with an increased prevalence in bacterial infections, suggesting a possible role directly regulating the immune response to bacterial pathogens.<ref>{{cite journal | vauthors = Choby JE, Monteith AJ, Himmel LE, Margaritis P, Shirey-Rice JK, Pruijssers A, Jerome RN, Pulley J, Skaar EP | title = A Phenome-Wide Association Study Uncovers a Pathological Role of Coagulation Factor X during <i>Acinetobacter baumannii</i> Infection | journal = Infection and Immunity | volume = 87 | issue = 5 | pages = IAI.00031–19 | date = March 2019 | pmid = 30782860 | pmc = 6479028 | doi = 10.1128/IAI.00031-19 }}</ref>

==Therapeutic use==
Factor X is part of [[fresh frozen plasma]] and the prothrombinase complex. There are two commercially available Factor X concentrates: "Factor X P Behring" manufactured by [[CSL Behring]],<ref>{{cite book | vauthors = Brooker M | date = April 2008 | title = Registry of Clotting Factor Concentrates | edition = Eighth | publisher = [[World Federation of Hemophilia]] }}</ref> and high purity Factor X '''Coagadex''' produced by [[Bio Products Laboratory]] and approved for use in the United States by the FDA in October 2015, and in the EU in March 2016, after earlier acceptance by CHMP and COMP.<ref>{{Cite press release|title = FDA approves first Factor X concentrate to treat patients with rare hereditary bleeding disorder|date = October 20, 2015|publisher = US FDA|url = https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm468038.htm|access-date = October 21, 2015|quote = Until today's orphan drug approval, no specific coagulation factor replacement therapy was available for patients with hereditary Factor X deficiency.|archive-url = https://web.archive.org/web/20151021125552/https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm468038.htm|archive-date = October 21, 2015|url-status = dead}}</ref><ref>{{cite web | title=Coagadex | website=U.S. Food and Drug Administration | url=https://www.fda.gov/vaccines-blood-biologics/approved-blood-products/coagadex | date=28 June 2017 | archive-date=22 July 2017 | archive-url=https://wayback.archive-it.org/7993/20170722071352/https://www.fda.gov/BiologicsBloodVaccines/BloodBloodProducts/ApprovedProducts/LicensedProductsBLAs/FractionatedPlasmaProducts/ucm468110.htm | url-status=unfit | access-date=2 April 2020}}</ref><ref>{{cite web | title=Coagadex | website=U.S. Food and Drug Administration | date=21 September 2018 | url=http://www.fda.gov/vaccines-blood-biologics/approved-blood-products/coagadex | access-date=2 April 2020 | archive-url=https://web.archive.org/web/20191217011130/https://www.fda.gov/vaccines-blood-biologics/approved-blood-products/coagadex | archive-date=17 December 2019 | url-status=dead }}</ref><ref>{{cite web | title=Coagadex EPAR | website=[[European Medicines Agency]] (EMA) | date=17 September 2018 | url=https://www.ema.europa.eu/en/medicines/human/EPAR/coagadex | access-date=21 April 2020 | archive-date=30 December 2019 | archive-url=https://web.archive.org/web/20191230151948/https://www.ema.europa.eu/en/medicines/human/EPAR/coagadex | url-status=live }}</ref>

Kcentra, manufactured by CSL Behring, is a concentrate containing coagulation Factors II, VII, IX and X, and antithrombotic Proteins C and S.<ref>{{cite web | title=Kcentra- prothrombin, coagulation factor vii human, coagulation factor ix human, coagulation factor x human, protein c, protein s human, and water kit | website=DailyMed | date=22 October 2018 | url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=eee1afb8-324c-42e4-8bf0-f0c9da5e6d42 | access-date=21 April 2020 | archive-date=25 March 2021 | archive-url=https://web.archive.org/web/20210325112536/https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=eee1afb8-324c-42e4-8bf0-f0c9da5e6d42 | url-status=live }}</ref>

==Use in biochemistry==
The factor Xa protease can be used in biochemistry to cleave off [[protein tag]]s that improve expression or purification of a protein of interest. Its preferred cleavage site (after the arginine in the sequence Ile-Glu/Asp-Gly-Arg, IEGR or IDGR) 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.

==Factor Xa==
[[File:Coagulation in vivo.png|right|thumb|350px|Blood coagulation pathways ''in vivo'' showing the central role played by thrombin]]
Factor Xa is the activated form of the [[coagulation factor]] X, also known as '''thrombokinase'''. Factor X is an [[enzyme]], a [[serine endopeptidase]], which plays a key role at several stages of the [[coagulation system]]. Factor X is [[Biosynthesis|synthesized]] in the [[liver]]. The most commonly used [[anticoagulants]] in clinical practice, [[warfarin]] and the [[heparin]] series of anticoagulants and [[fondaparinux]], act to inhibit the action of Factor Xa in various degrees.

Traditional models of coagulation developed in the 1960s envisaged two separate cascades, the extrinsic [[tissue factor|(tissue factor (TF))]] pathway and the intrinsic pathway. These pathways converge to a common point, the formation of the Factor Xa/Va complex which together with [[calcium]] and bound on a [[phospholipids]] surface, generate [[thrombin|thrombin (Factor IIa)]] from [[prothrombin|prothrombin (Factor II)]].

A new model, the cell-based model of anticoagulation appears to explain more fully the steps in coagulation. This model has three stages: 1) initiation of coagulation on TF-bearing cells, 2) amplification of the procoagulant signal by thrombin generated on the TF-bearing cell and 3) propagation of thrombin generation on the [[platelet]] surface. Factor Xa plays a key role in all three of these stages.<ref name="HOCNA">{{cite journal | vauthors = Hoffman M, Monroe DM | title = Coagulation 2006: a modern view of hemostasis | journal = Hematology/Oncology Clinics of North America | volume = 21 | issue = 1 | pages = 1–11 | date = February 2007 | pmid = 17258114 | doi = 10.1016/j.hoc.2006.11.004 }}</ref>

In stage 1, [[Factor VII]] binds to the [[transmembrane protein]] TF on the surface of cells and is converted to Factor VIIa. The result is a Factor VIIa/TF complex, which catalyzes the activation of Factor X and [[Factor IX]]. Factor Xa formed on the surface of the TF-bearing cell interacts with [[Factor V]]a to form the [[prothrombinase| prothrombinase complex]] which generates small amounts of thrombin on the surface of TF-bearing cells.

In stage 2, the amplification stage, if enough thrombin has been generated, then activation of platelets and platelet-associated [[cofactor (biochemistry)|cofactors]] occurs.

In stage 3, thrombin generation, [[Factor XI]]a activates free Factor IX on the surface of activated platelets. The activated Factor IXa with [[Factor VIII]]a forms the [[tenase|"tenase" complex]]. This "tenase" complex activates more Factor X, which in turn forms new prothrombinase complexes with Factor Va. Factor Xa is the prime component of the prothrombinase complex which converts large amounts of [[prothrombin]]—the "thrombin burst". Each molecule of Factor Xa can generate 1000 molecules of thrombin. This large burst of thrombin is responsible for [[fibrin]] [[polymerization]] to form a [[thrombus]].

Factor Xa also plays a role in other biological processes that are not directly related to coagulation, like wound healing, tissue remodelling, inflammation, angiogenesis and atherosclerosis.

Inhibition of the synthesis or activity of Factor X is the mechanism of action for many anticoagulants in use today. Warfarin, a synthetic derivative of [[coumarin]], is the most widely used oral anticoagulant in the US. In some European countries, other coumarin derivatives ([[phenprocoumon]] and [[acenocoumarol]]) are used. These agents known as [[vitamin K antagonists]] (VKA), inhibit the vitamin K-dependent carboxylation of Factors II (prothrombin), VII, IX, X in the hepatocyte. This carboxylation after the translation is essential for the physiological activity.<ref>{{cite book |last=Golan |first=D. E. |year=2012 |title=Principles of Pharmacology The Pathophysiologic Basis of Drug Therapy |location=Philadelphia |publisher=Lippincott Williams & Wilkins |page=387 |isbn=978-1-4511-1805-6}}</ref>

Heparin (unfractionated heparin) and its derivatives [[low molecular weight heparin|low molecular weight heparin (LMWH)]] bind to a [[blood plasma|plasma]] cofactor, [[antithrombin|antithrombin (AT)]] to inactivate several coagulation factors IIa, Xa, XIa and XIIa. The affinity of unfractionated heparin and the various LMWHs for Factor Xa varies considerably. The efficacy of heparin-based anticoagulants increases as selectivity for Factor Xa increases. LMWH shows increased inactivation of Factor Xa compared to unfractionated heparin, and fondaparinux, an agent based on the critical pentasacharide sequence of heparin, shows more selectivity than LMWH. This inactivation of Factor Xa by heparins is termed "indirect" since it relies on the presence of AT and not a direct interaction with Factor Xa.

Recently a new series of specific, direct acting inhibitors of Factor Xa has been developed. These include the drugs [[rivaroxaban]], [[apixaban]], [[betrixaban]], LY517717, [[darexaban]] (YM150), [[edoxaban]] and 813893. These agents have several theoretical advantages over current therapy. They may be given orally. They have rapid onset of action. And they may be more effective against Factor Xa in that they inhibit both free Factor Xa and Factor Xa in the prothrombinase complex.<ref name="ATVB">{{cite journal | vauthors = Turpie AG | title = Oral, direct factor Xa inhibitors in development for the prevention and treatment of thromboembolic diseases | journal = Arteriosclerosis, Thrombosis, and Vascular Biology | volume = 27 | issue = 6 | pages = 1238–1247 | date = June 2007 | pmid = 17379841 | doi = 10.1161/ATVBAHA.107.139402 | s2cid = 2998452 | citeseerx = 10.1.1.536.872 }}</ref>

==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 (1921) and a Miss Audrey Prower (1934).  At that time, those investigators could not know that the human genetic defect they had identified would be found in the previously characterized enzyme called thrombokinase.

Thrombokinase was the name coined by Paul Morawitz in 1904 to describe the substance that converted prothrombin to thrombin and caused blood to clot.<ref>{{cite journal |last1=Morawitz |first1=Paul |title=Beitrage zur Kenntnis der Blutgerinnung |journal=Deutsches Archiv für Klinische Medizin |volume=79 |pages=432–442}}</ref>  That name embodied an important new concept in understanding blood coagulation – that an enzyme was critically important in the activation of prothrombin.  Morawitz believed that his enzyme came from cells such as platelets yet, in keeping with the state of knowledge about enzymes at that time, he had no clear idea about the chemical nature of his thrombokinase or its mechanism of action.  Those uncertainties led to decades during which the terms thrombokinase and thromboplastin were both used to describe the activator of prothrombin and led to controversy about its chemical nature and origin.<ref>{{cite journal | vauthors = Milstone JH | title = On the evolution of blood clotting theory | journal = Medicine | volume = 31 | issue = 4 | pages = 411–447 | date = December 1952 | pmid = 13012730 | doi = 10.1097/00005792-195212000-00004 | doi-access = free }}</ref>

In 1947, J Haskell Milstone isolated a proenzyme from bovine plasma which, when activated, converted prothrombin to thrombin.  Following Morawitz’s designation, he called it prothrombokinase <ref>{{cite journal | vauthors = Milstone JH | title = Prothrombokinase and the Three Stages of Blood Coagulation | journal = Science | volume = 106 | issue = 2762 | pages = 546–547 | date = December 1947 | pmid = 17741228 | doi = 10.1126/science.106.2762.546-a | s2cid = 35643683 | bibcode = 1947Sci...106..546M }}</ref> and by 1951 had purified the active enzyme, thrombokinase.  Over the next several years he showed  that thrombokinase was a proteolytic enzyme that, by itself, could activate prothrombin.  Its activity was greatly enhanced by addition of calcium, other serum factors, and tissue extracts,<ref>{{cite journal | vauthors = Milstone LM | title = Factor Xa: Thrombokinase from Paul Morawitz to J Haskell Milstone | journal = Journal of Thrombosis and Thrombolysis | volume = 52 | issue = 2 | pages = 364–370 | date = August 2021 | pmid = 33484373 | doi = 10.1007/s11239-021-02387-6 | s2cid = 231682954 }}</ref> which represented the thromboplastins that promoted the conversion of prothrombin to thrombin by their interaction with thrombokinase.  In 1964 Milstone summarized his work and that of others: “There are many chemical reactions which are so slow that they would not be of physiological use if they were not accelerated by enzymes.  We are now confronted with a reaction, catalyzed by an enzyme, which is still too slow unless aided by accessory factors.” <ref>{{cite journal | vauthors = Milstone JH, Oulianoff N, Milstone VK | title = Thrombokinase as prime activator of prothrombin: historical perspectives and present status | journal = The Journal of General Physiology | volume = 47 | issue = 2 | pages = 315–327 | date = November 1963 | pmid = 14080818 | pmc = 2195336 | doi = 10.1085/jgp.47.2.315 }}</ref>

== Interactions ==

Factor X has been shown to [[Protein-protein interaction|interact]] with [[Tissue factor pathway inhibitor]].<ref name=pmid3422166>{{cite journal | vauthors = Broze GJ, Warren LA, Novotny WF, Higuchi DA, Girard JJ, Miletich JP | 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 = 335–343 | date = February 1988 | pmid = 3422166 | doi = 10.1182/blood.V71.2.335.335 | doi-access = free }}</ref>

== References ==
{{Reflist}}

== Further reading ==
{{Refbegin | 2}}
* {{cite journal | vauthors = Cooper DN, Millar DS, Wacey A, Pemberton S, Tuddenham EG | title = Inherited factor X deficiency: molecular genetics and pathophysiology | journal = Thrombosis and Haemostasis | volume = 78 | issue = 1 | pages = 161–172 | date = July 1997 | pmid = 9198147 | doi = 10.1055/s-0038-1657520 | s2cid = 27129058 }}
* {{cite journal | vauthors = Hassan HJ, Leonardi A, Chelucci C, Mattia G, Macioce G, Guerriero R, Russo G, Mannucci PM, Peschle C | title = Blood coagulation factors in human embryonic-fetal development: preferential expression of the FVII/tissue factor pathway | journal = Blood | volume = 76 | issue = 6 | pages = 1158–1164 | date = September 1990 | pmid = 1698100 | doi = 10.1182/blood.V76.6.1158.1158 | doi-access = free }}
* {{cite journal | vauthors = Messier TL, Pittman DD, Long GL, Kaufman RJ, Church WR | 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 = 291–294 | date = March 1991 | pmid = 1902434 | doi = 10.1016/0378-1119(91)90141-W }}
* {{cite journal | vauthors = Krishnaswamy S | title = Prothrombinase complex assembly. Contributions of protein-protein and protein-membrane interactions toward complex formation | journal = The Journal of Biological Chemistry | volume = 265 | issue = 7 | pages = 3708–3718 | date = March 1990 | pmid = 2303476 | doi = 10.1016/S0021-9258(19)39652-8 | doi-access = free }}
* {{cite journal | vauthors = España F, Berrettini M, Griffin JH | title = Purification and characterization of plasma protein C inhibitor | journal = Thrombosis Research | volume = 55 | issue = 3 | pages = 369–384 | date = August 1989 | pmid = 2551064 | doi = 10.1016/0049-3848(89)90069-8 }}
* {{cite journal | vauthors = Fung MR, Hay CW, MacGillivray RT | title = Characterization of an almost full-length cDNA coding for human blood coagulation factor X | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 82 | issue = 11 | pages = 3591–3595 | date = June 1985 | pmid = 2582420 | pmc = 397831 | doi = 10.1073/pnas.82.11.3591 | doi-access = free | bibcode = 1985PNAS...82.3591F }}
* {{cite journal | vauthors = Jagadeeswaran P, Reddy SV, Rao KJ, Hamsabhushanam K, Lyman G | title = Cloning and characterization of the 5' end (exon 1) of the gene encoding human factor X | journal = Gene | volume = 84 | issue = 2 | pages = 517–519 | date = December 1989 | pmid = 2612918 | doi = 10.1016/0378-1119(89)90529-5 }}
* {{cite journal | vauthors = Reddy SV, Zhou ZQ, Rao KJ, Scott JP, Watzke H, High KA, Jagadeeswaran P | title = Molecular characterization of human factor XSan Antonio | journal = Blood | volume = 74 | issue = 5 | pages = 1486–1490 | date = October 1989 | pmid = 2790181 | doi = 10.1182/blood.V74.5.1486.1486 | doi-access = free }}
* {{cite journal | vauthors = 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 = 311–314 | year = 1986 | pmid = 3011603 | doi = 10.1016/0378-1119(86)90112-5 }}
* {{cite journal | vauthors = Broze GJ, Warren LA, Novotny WF, Higuchi DA, Girard JJ, Miletich JP | 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 = 335–343 | date = February 1988 | pmid = 3422166 | doi = 10.1182/blood.V71.2.335.335 | doi-access = free }}
* {{cite journal | vauthors = Gilgenkrantz S, Briquel ME, André E, Alexandre P, Jalbert P, Le Marec B, Pouzol P, Pommereuil M | title = Structural genes of coagulation factors VII and X located on 13q34 | journal = Annales de Génétique | volume = 29 | issue = 1 | pages = 32–35 | year = 1986 | pmid = 3487272 }}
* {{cite journal | vauthors = 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 = 5098–5102 | date = September 1986 | pmid = 3768336 | doi = 10.1021/bi00366a018 }}
* {{cite journal | vauthors = Leytus SP, Chung DW, Kisiel W, Kurachi K, Davie EW | title = Characterization of a cDNA coding for human factor X | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 81 | issue = 12 | pages = 3699–3702 | date = June 1984 | pmid = 6587384 | pmc = 345286 | doi = 10.1073/pnas.81.12.3699 | doi-access = free | bibcode = 1984PNAS...81.3699L }}
* {{cite journal | vauthors = McMullen BA, Fujikawa K, Kisiel W, Sasagawa T, Howald WN, Kwa EY, Weinstein B | 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 = 2875–2884 | date = June 1983 | pmid = 6871167 | doi = 10.1021/bi00281a016 }}
* {{cite journal | vauthors = Marchetti G, Castaman G, Pinotti M, Lunghi B, Di Iasio MG, Ruggieri M, Rodeghiero F, Bernardi F | 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 = British Journal of Haematology | volume = 90 | issue = 4 | pages = 910–915 | date = August 1995 | pmid = 7669671 | doi = 10.1111/j.1365-2141.1995.tb05214.x | s2cid = 29324903 }}
* {{cite journal | vauthors = Morgenstern KA, Sprecher C, Holth L, Foster D, Grant FJ, Ching A, Kisiel W | 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 = 3432–3441 | date = March 1994 | pmid = 8136380 | doi = 10.1021/bi00177a037 }}
* {{cite journal | vauthors = Heeb MJ, Rosing J, Bakker HM, Fernandez JA, Tans G, Griffin JH | title = Protein S binds to and inhibits factor Xa | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 91 | issue = 7 | pages = 2728–2732 | date = March 1994 | pmid = 8146182 | pmc = 43443 | doi = 10.1073/pnas.91.7.2728 | doi-access = free | bibcode = 1994PNAS...91.2728H }}
* {{cite journal | vauthors = 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 = European Journal of Biochemistry | volume = 218 | issue = 1 | pages = 153–163 | date = November 1993 | pmid = 8243461 | doi = 10.1111/j.1432-1033.1993.tb18361.x | doi-access = free }}
* {{cite journal | vauthors = Padmanabhan K, Padmanabhan KP, Tulinsky A, Park CH, Bode W, Huber R, Blankenship DT, Cardin AD, Kisiel W | title = Structure of human des(1-45) factor Xa at 2.2 A resolution | journal = Journal of Molecular Biology | volume = 232 | issue = 3 | pages = 947–966 | date = August 1993 | pmid = 8355279 | doi = 10.1006/jmbi.1993.1441 }}
* {{cite journal | vauthors = Sinha U, Wolf DL | title = Carbohydrate residues modulate the activation of coagulation factor X | journal = The Journal of Biological Chemistry | volume = 268 | issue = 5 | pages = 3048–3051 | date = February 1993 | pmid = 8428982 | doi = 10.1016/S0021-9258(18)53657-7 | doi-access = free }}
{{Refend}}

== Further reading ==
{{refbegin}} 
* {{cite web | vauthors = Schwartz RA, Steen CJ, Gascon P, Schick P | date = 18 March 2024 | veditors = Talavera F, Sacher RA, Thiagarajan P | work = MedScape | publisher = WebMD LLC | title = Factor X Deficiency | url = https://emedicine.medscape.com/article/209867-overview#}}
{{refend}}

== External links ==
* {{cite web | title = Summary for peptidase S01.216: coagulation factor Xa | url = https://www.ebi.ac.uk/merops/cgi-bin/pepsum?id=S01.216 | publisher = European Molecular Biology Laboratory (EMBL) | work = [[MEROPS]] }}
* {{cite web | title = Factor X deficiency | url = https://www.hemophilia.ca/factor-x-deficiency/ | work = Canadian Hemophilia Society | date = 14 April 2018 }}

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[[Category:EC 3.4.21]]
[[Category:Coagulation system]]