blood coagulation factor XII

• 血液凝固第XII因子

WordNet

1. be a contributing factor; "make things factor into a companys profitability"
2. any of the numbers (or symbols) that form a product when multiplied together
3. an independent variable in statistics
4. anything that contributes causally to a result; "a number of factors determined the outcome"
5. consider as relevant when making a decision; "You must factor in the recent developments" (同)factor in, factor out
6. resolve into factors; "a quantum computer can factor the number 15" (同)factor in, factor out
7. smear with blood, as in a hunting initiation rite, where the face of a person is smeared with the blood of the kill
8. temperament or disposition; "a person of hot blood"
9. people viewed as members of a group; "we need more young blood in this organization"
10. the fluid (red in vertebrates) that is pumped through the body by the heart and contains plasma, blood cells, and platelets; "blood carries oxygen and nutrients to the tissues and carries away waste products"; "the ancients believed that blood was the sea
11. an event known to have happened or something known to have existed; "your fears have no basis in fact"; "how much of the story is fact and how much fiction is hard to tell"
12. a concept whose truth can be proved; "scientific hypotheses are not facts"
13. a piece of information about circumstances that exist or events that have occurred; "first you must collect all the facts of the case"
14. a statement or assertion of verified information about something that is the case or has happened; "he supported his argument with an impressive array of facts"
15. the 24th letter of the Roman alphabet (同)x, ex

PrepTutorEJDIC

1. (…の)『要因』,(…を生み出す)要素《+『in』+『名』(do『ing』)》 / 囲数,約数 / 代理人,《おもに英》仲買人 / =factorize
2. 『血』,『血』液 / 流血(bloodshed);殺人 / 気質,気性,血気,血潮 / 『血統』,血縁(kinship);生まれ,家柄;《the~》王家の血統 / (人種・出身国の)系 / 〈人〉‘に'初めての経験をさせる / 〈猟犬〉‘に'初めて獲物を血を味わわせる
3. 〈C〉『事実』,実際にある(あった)事 / 〈U〉真相,真実(truth) / 《the~》(法律用語で)犯行
4. Christ / Christian
5. 純血の,純種の / 《複合語を作って》「…の血(性質)を持った」の意を表す

Wikipedia preview

出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2014/03/27 17:05:27」(JST)

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[Wiki en表示]

Coagulation factor XII (Hageman factor)
Available structures PDB Ortholog search: PDBe, RCSB List of PDB id codes 4BDW, 4BDX
Identifiers
Symbols	F12 (; HAE3; HAEX; HAF)
External IDs	OMIM: 610619 MGI: 1891012 HomoloGene: 425 ChEMBL: 2821 GeneCards: F12 Gene
EC number	3.4.21.38
Gene Ontology Molecular function • serine-type endopeptidase activity • protein binding • misfolded protein binding • serine-type aminopeptidase activity Cellular component • extracellular region • extracellular space • plasma membrane Biological process • plasma kallikrein-kinin cascade • Factor XII activation • proteolysis • blood coagulation • blood coagulation, intrinsic pathway • positive regulation of plasminogen activation • protein processing • protein autoprocessing • positive regulation of blood coagulation • zymogen activation • fibrinolysis • innate immune response • response to misfolded protein • positive regulation of fibrinolysis Sources: Amigo / QuickGO
RNA expression pattern
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	2161	58992
Ensembl	ENSG00000131187	ENSMUSG00000021492
UniProt	P00748	Q80YC5
RefSeq (mRNA)	NM_000505	NM_021489
RefSeq (protein)	NP_000496	NP_067464
Location (UCSC)	Chr 5: 176.83 – 176.84 Mb	Chr 13: 55.42 – 55.43 Mb
PubMed search	[1]	[2]

Coagulation factor XII, also known as Hageman factor, is a plasma protein. It is the zymogen form of factor XIIa, an enzyme (EC 3.4.21.38) of the serine protease (or serine endopeptidase) class. In humans, factor XII is encoded by the F12 gene.

Structure

Human Factor XII is 596 amino acids long and consists of two domains, the heavy chain (353 residues) and light chain (243 residues) held together by a disulfide bond. It is 80,000 daltons. Its heavy chain contains two fibronectin-type domains (type I and II), two epidermal growth factor-like domains, a kringle domain, and a proline-rich region, and its light chain contains the protease domain. Recently, the structure of the FnI-EGF-like tandem domain of coagulation factor XII was solved by x-ray crystallography.

Function

Factor XII is part of the coagulation cascade and activates factor XI and prekallikrein in vitro. Factor XII itself is activated to factor XIIa by negatively charged surfaces, such as glass. This is the starting point of the intrinsic pathway, which is now regarded as an obsolete term, because of the fact that there is no intrinsic pathway in vivo. Factor XII is only used to start coagulation cascades in laboratory studies and is considered to have little to no effect on coagulation in vivo.

The coagulation cascade.

In vivo, factor XII is activated by contact to polyanions. Activated platelets secrete inorganic polymers, polyphosphates. Contact to polyphosphates activates factor XII and initiates fibrin formation by the intrinsic pathway of coagulation with critical importance for thrombus formation. Targeting polyphosphates with phosphatases interfered with procoagulant activity of activated platelets and blocked platelet-induced thrombosis in mice. Addition of polyphosphates restored defective plasma clotting of Hermansky-Pudlak syndrome patients, indicating that the inorganic polymer is the endogenous factor XII activator in vivo. Platelet polyphosphate-driven factor XII activation provides the link from primary hemostasis (formation of a platelet plug) to secondary hemostasis (fibrin meshwork formation).

Genetics

The gene for factor XII is located on the tip of the long arm of the fifth chromosome (5q33-qter).

Role in disease

Factor XII deficiency is a rare disorder that is inherited in an autosomal recessive manner. Unlike other clotting factor deficiencies, factor XII deficiency is totally asymptomatic and does not cause excess bleeding. Mice lacking the gene for factor XII, however, are less susceptible to thrombosis. The protein seems to be involved in the later stages of clot formation rather than the first occlusion of damages in the blood vessel wall.

Factor XII does play an important role in clot formation during in vitro measurements of the partial thromboplastin time, which causes these measurements to be markedly prolonged in patients with factor XII deficiency, usually well beyond even what is seen in hemophilia A, hemophilia B, or factor XI deficiency. As a result, the main concern related to factor XII deficiency is the unnecessary testing, delay in care, worry, etc. that may be prompted by the abnormal lab result. All of this, including the mechanism of inheritance, also holds true for the other contact factors, prekallikrein (Fletcher factor) and high molecular weight kininogen.

Excess levels of factor XII can predispose individuals towards greater risk of venous thrombosis due to factor XII's role as one of the catalysts for conversion of plasminogen to its active fibrinolytic form of plasmin.

Factor XII is also activated by endotoxins, especially lipid A.

History

Hageman factor was first discovered in 1955 when a routine preoperative blood sample of the 37-year-old railroad brakeman John Hageman (1918) was found to have prolonged clotting time in test tubes, even though he had no hemorrhagic symptoms. Hageman was then examined by Dr. Oscar Ratnoff, who found that Mr. Hageman lacked a previously unidentified clotting factor. Dr. Ratnoff later found that the Hageman factor deficiency is an autosomal recessive disorder, after examining several related people who had the deficiency. Paradoxically, pulmonary embolism contributed to Hageman's death after an occupational accident. Since then, case studies and clinical studies identified an association between thrombosis and Factor XII deficiency. Hepatocytes express blood coagulation factor XII.

References

Further reading

• Girolami A, Randi ML, Gavasso S, et al. (2005). "The occasional venous thromboses seen in patients with severe (homozygous) FXII deficiency are probably due to associated risk factors: a study of prevalence in 21 patients and review of the literature". J. Thromb. Thrombolysis 17 (2): 139–43. doi:10.1023/B:THRO.0000037670.42776.cd. PMID 15306750. 
• Renné T, Gailani D (2007). "Role of Factor XII in hemostasis and thrombosis: clinical implications". Expert review of cardiovascular therapy 5 (4): 733–41. doi:10.1586/14779072.5.4.733. PMID 17605651. 
• Harris RJ, Ling VT, Spellman MW (1992). "O-linked fucose is present in the first epidermal growth factor domain of factor XII but not protein C". J. Biol. Chem. 267 (8): 5102–7. PMID 1544894. 
• McMullen BA, Fujikawa K, Davie EW (1991). "Location of the disulfide bonds in human plasma prekallikrein: the presence of four novel apple domains in the amino-terminal portion of the molecule". Biochemistry 30 (8): 2050–6. doi:10.1021/bi00222a007. PMID 1998666. 
• Miyata T, Kawabata S, Iwanaga S, et al. (1989). "Coagulation factor XII (Hageman factor) Washington D.C.: inactive factor XIIa results from Cys-571----Ser substitution". Proc. Natl. Acad. Sci. U.S.A. 86 (21): 8319–22. doi:10.1073/pnas.86.21.8319. PMC 298272. PMID 2510163. 
• Bernardi F, Marchetti G, Patracchini P, et al. (1987). "Factor XII gene alteration in Hageman trait detected by TaqI restriction enzyme". Blood 69 (5): 1421–4. PMID 2882793. 
• Cool DE, MacGillivray RT (1987). "Characterization of the human blood coagulation factor XII gene. Intron/exon gene organization and analysis of the 5'-flanking region". J. Biol. Chem. 262 (28): 13662–73. PMID 2888762. 
• Que BG, Davie EW (1986). "Characterization of a cDNA coding for human factor XII (Hageman factor)". Biochemistry 25 (7): 1525–8. doi:10.1021/bi00355a009. PMID 3011063. 
• Royle NJ, Nigli M, Cool D, et al. (1988). "Structural gene encoding human factor XII is located at 5q33-qter". Somat. Cell Mol. Genet. 14 (2): 217–21. doi:10.1007/BF01534407. PMID 3162339. 
• Citarella F, Tripodi M, Fantoni A, et al. (1989). "Assignment of human coagulation factor XII (fXII) to chromosome 5 by cDNA hybridization to DNA from somatic cell hybrids". Hum. Genet. 80 (4): 397–8. doi:10.1007/BF00273661. PMID 3198120. 
• Henry ML, Everson B, Ratnoff OD (1988). "Inhibition of the activation of Hageman factor (factor XII) by beta 2-glycoprotein I". J. Lab. Clin. Med. 111 (5): 519–23. PMID 3361230. 
• Chung DW, Fujikawa K, McMullen BA, Davie EW (1986). "Human plasma prekallikrein, a zymogen to a serine protease that contains four tandem repeats". Biochemistry 25 (9): 2410–7. doi:10.1021/bi00357a017. PMID 3521732. 
• Tripodi M, Citarella F, Guida S, et al. (1986). "cDNA sequence coding for human coagulation factor XII (Hageman)". Nucleic Acids Res. 14 (7): 3146. doi:10.1093/nar/14.7.3146. PMC 339730. PMID 3754331. 
• Cool DE, Edgell CJ, Louie GV, et al. (1985). "Characterization of human blood coagulation factor XII cDNA. Prediction of the primary structure of factor XII and the tertiary structure of beta-factor XIIa". J. Biol. Chem. 260 (25): 13666–76. PMID 3877053. 
• McMullen BA, Fujikawa K (1985). "Amino acid sequence of the heavy chain of human alpha-factor XIIa (activated Hageman factor)". J. Biol. Chem. 260 (9): 5328–41. PMID 3886654. 
• de Grouchy J, Turleau C (1975). "Tentative localization of a Hageman (Factor XII) locus on 7q, probably the 7q35 band". Humangenetik 24 (3): 197–200. PMID 4140832. 
• Fujikawa K, McMullen BA (1983). "Amino acid sequence of human beta-factor XIIa". J. Biol. Chem. 258 (18): 10924–33. PMID 6604055. 
• Hovinga JK, Schaller J, Stricker H, et al. (1994). "Coagulation factor XII Locarno: the functional defect is caused by the amino acid substitution Arg 353-->Pro leading to loss of a kallikrein cleavage site". Blood 84 (4): 1173–81. PMID 8049433. 
• Schloesser M, Hofferbert S, Bartz U, et al. (1996). "The novel acceptor splice site mutation 11396(G-->A) in the factor XII gene causes a truncated transcript in cross-reacting material negative patients". Hum. Mol. Genet. 4 (7): 1235–7. doi:10.1093/hmg/4.7.1235. PMID 8528215. 
• Hofferbert S, Müller J, Köstering H, et al. (1996). "A novel 5'-upstream mutation in the factor XII gene is associated with a TaqI restriction site in an Alu repeat in factor XII-deficient patients". Hum. Genet. 97 (6): 838–41. doi:10.1007/BF02346200. PMID 8641707. 

External links

• The MEROPS online database for peptidases and their inhibitors: S01.211
• Factor XII at the US National Library of Medicine Medical Subject Headings (MeSH)

UpToDate Contents

全文を閲覧するには購読必要です。 To read the full text you will need to subscribe.

• 1. 血漿分画製剤および組換えDNA産生凝固因子 plasma derivatives and recombinant dna produced coagulation factors
• 2. 静脈血栓症の原因の概要 overview of the causes of venous thrombosis
• 3. 胎児の採血 fetal blood sampling
• 4. 肝臓の合成能の検査（アルブミン、凝固因子、プロトロンビン時間など） tests of the livers biosynthetic capacity eg albumin coagulation factors prothrombin time
• 5. 重症患者における血液製剤の使用 use of blood products in the critically ill

English Journal

• Angioedema.

• Bork K.Author information Department of Dermatology, Johannes Gutenberg University, Langenbeckstr. 1, 55131 Mainz, Germany. Electronic address: bork@hautklinik.klinik.uni-mainz.de.AbstractUrticarial wheals and angioedema are 2 different clinical symptoms. Both belong to various disease entities, and may occur in combination or be isolated. Increased vasodilation and vasopermeability is a common feature. Histamine and bradykinin are well-known mediators. For clinical purposes, 3 groups of diseases can be differentiated: diseases with urticaria and angioedema, diseases with angioedema alone, and diseases with urticarial lesions without angioedema. The article presents an overview of these groups and the role of the main mediators, and the clinical features of urticaria and angioedema.
• Immunology and allergy clinics of North America.Immunol Allergy Clin North Am.2014 Feb;34(1):23-31. doi: 10.1016/j.iac.2013.09.004. Epub 2013 Oct 20.
• Urticarial wheals and angioedema are 2 different clinical symptoms. Both belong to various disease entities, and may occur in combination or be isolated. Increased vasodilation and vasopermeability is a common feature. Histamine and bradykinin are well-known mediators. For clinical purposes, 3 group
• PMID 24262687

• Lack of secondary microthrombosis after thrombin-induced stroke in mice and non-human primates.

• Gauberti M, de Lizarrondo SM, Orset C, Vivien D.Author information Inserm, Inserm UMR-S U919, "Serine Proteases and Pathophysiology of the Neurovascular Unit", Université Caen Basse-Normandie, GIP Cyceron, Caen, France.AbstractBACKGROUND: Secondary microthrombosis is a major pathophysiological mechanism leading to brain damage following transient mechanical vascular occlusion (TMVO), the most widely used experimental stroke model. Whether secondary microthrombosis also occurs in non-TMVO stroke models represents an important issue for clinical translation of anti-microthrombosis therapeutic strategies.
• Journal of thrombosis and haemostasis : JTH.J Thromb Haemost.2013 Dec 16. doi: 10.1111/jth.12487. [Epub ahead of print]
• BACKGROUND: Secondary microthrombosis is a major pathophysiological mechanism leading to brain damage following transient mechanical vascular occlusion (TMVO), the most widely used experimental stroke model. Whether secondary microthrombosis also occurs in non-TMVO stroke models represents an import
• PMID 24354644

• Factor XIIa inhibition by Infestin-4: in vitro mode of action and in vivo antithrombotic benefit.

• Xu Y, Cai TQ, Castriota G, Zhou Y, Hoos L, Jochnowitz N, Loewrigkeit C, Cook JA, Wickham A, Metzger JM, Ogletree ML, Seiffert DA, Chen Z.Author information Zhu Chen, PhD, Cardiometabolic Diseases, Merck Research Laboratories, K15-3A-309, Galloping Hill Road, Kenilworth, NJ 07033, USA, Tel.: +1 908 740 0642, E-mail: zhu_chen@merck.com.AbstractCoagulation factor XII (FXII) plays a central role in initiating the intrinsic cascade of blood coagulation. Purified recombinant Human Albumin-tagged Infestin-4 (rHA-Infestin-4) is a recently described FXIIa inhibitor that displayed strong anticoagulant activity without compromising haemostasis in several animal models. We pursued detailed in vitro characterisation of rHA-Infestin-4 and demonstrated that it is a competitive inhibitor of FXIIa with slow on and off rate constants for binding (kon=5x10⁵ M⁻¹s⁻¹, koff=6x10⁻⁴ s⁻¹), it can block FXIIa activation of its physiological substrates (plasma prekallikrein and FXI), and it can inhibit ellagic acid-triggered thrombin generation in plasma. Potency and selectivity profiling in enzyme assays suggest that rHA-Infestin-4 is indeed highly potent on FXIIa (IC50=0.3 ± 0.06, 1.5 ± 0.06, 1.2 ± 0.09 nM, for human, rat, and rabbit FXIIa, respectively) with at least >100-fold selectivity against factors IIa, Xa, IXa, XIa, VIIa, and plasma kallikrein in all three species. rHA-Infestin-4 dose-dependently and markedly reduced clot weight in the arteriovenous shunt thrombosis model in rats and rabbits, accompanied with minimal increase in cuticle bleeding times in either species. rHA-Infestin-4 treatment at 5 mg/kg in rabbit resulted in a 13% reduction in ex vivo FXa activity, demonstrating a modest off-target effect. In summary, our findings confirmed and extended previous reports that inhibition of FXIIa by rHA-Infestin-4 can produce strong antithrombotic efficacy while preserving haemostasis. Our comprehensive selectivity profiling, mode of action, and kinetic studies of rHA-Infestin-4 reveal limitations of this molecule and offer new perspectives on any potential effort of discovering novel FXIIa inhibitors.
• Thrombosis and haemostasis.Thromb Haemost.2013 Dec 12;111(4). [Epub ahead of print]
• Coagulation factor XII (FXII) plays a central role in initiating the intrinsic cascade of blood coagulation. Purified recombinant Human Albumin-tagged Infestin-4 (rHA-Infestin-4) is a recently described FXIIa inhibitor that displayed strong anticoagulant activity without compromising haemostasis in
• PMID 24336918

Japanese Journal

• 内因系血液凝固研究の現状 : XII因子, XI因子及び高分子キニノーゲンの欠損マウスについて

• 中冨 靖,中垣 智弘
• 日本血栓止血学会誌 = The Journal of Japanese Society on Thrombosis and Hemostasis 20(3), 323-328, 2009-06-01
• NAID 10026117562

• 飼育下マイルカ科鯨類4種及びキタオットセイの血液凝固に関する測定値

• 香山 薫,米崎 史郎
• 哺乳類科学 = Mammalian Science 47(2), 221-225, 2007-12-30
• … その結果，測定を実施した鯨目全種において，血液凝固に関するスクリーニングテストで，ヒトと比較して活性化部分トロンボプラスチン時間（APTT）の顕著な延長が認められ，血液凝固因子活性の測定では第XII因子（Hageman因子）活性の顕著な低値が確認された．これらが，鯨類の血液凝固時間の延長要因に関係すると考えられる．一方，血液凝固時間の延長のない食肉類のキタオットセイでは，鯨類やヒトと異なる結 …
• NAID 10020029180

• Subdural Hematoma in a Patient With Hageman Trait : Case Report

• KASPERA Wojciech,ROTHKEGEL Katarzyna,STADNICKI Antoni
• Neurologia medico-chirurgica 45(12), 640-644, 2005-12-15
• … A 61-year-old man with severe factor XII deficiency presented with a subdural hematoma appearing as mixed but mainly high density by computed tomography in the left frontotemporoparietal region. … Clotting system study showed less than 1% functional activity of factor XII, whereas the levels of the other clotting factors were within the normal ranges. …
• NAID 110002556734

Related Links

• F12 - coagulation factor XII - Genetics Home Reference

The F12 gene provides instructions for making a protein called coagulation factor XII. Coagulation factors are a group of related proteins that are essential for normal blood clotting (coagulation). After an injury, clots protect ...

• F12 coagulation factor XII (Hageman factor) [ (human)]

This gene encodes coagulation factor XII which circulates in blood as a zymogen. This single chain zymogen is converted to a two-chain serine protease with an heavy chain (alpha-factor XIIa) and a light chain. The heavy ...

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★リンクテーブル★

リンク元	「血液凝固第XII因子」
拡張検索	「blood coagulation factor XIII」
関連記事	「fact」「factor」「coagulation factor」「X」「blood」

「血液凝固第XII因子」

　　[★]

英

blood coagulation factor XII

「blood coagulation factor XIII」

　　[★]

• 血液凝固第XIII因子

関

coagulation factor XIII、factor XIII

「fact」

　　[★]

• n.

• 事実、現状、実際、実態

関

actual、actually、in fact、in practice、indeed、practically

　 　 　 　 　

「factor」

　　[★]

• n.

• 因子、要因、要素、ファクター

関

element、elementary、factorial、parameter

　 　 　 　 　 　 　

「coagulation factor」

　　[★] 血液凝固因子

同

coagulation factors

「X」

　　[★] キサントシン, xanthosine 　 　

「blood」

　　[★] 血液