proaccelerin

第V因子 factor V 　

WordNet

1. a coagulation factor (同)prothrombin accelerator, accelerator factor, factor_V

Wikipedia preview

出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2015/12/01 00:44:46」(JST)

wiki en

[Wiki en表示]

This article is about the blood coagulation protein. For the software company, see Factor 5.

Coagulation factor V (proaccelerin, labile factor)
PDB rendering based on 1czs.
Available structures PDB Ortholog search: PDBe, RCSB List of PDB id codes 1CZS, 1CZT, 1CZV, 1FV4, 1Y61, 3P6Z, 3P70, 3S9C
Identifiers
Symbols	F5 ; FVL; PCCF; RPRGL1; THPH2
External IDs	OMIM: 612309 MGI: 88382 HomoloGene: 104 ChEMBL: 3618 GeneCards: F5 Gene
Gene ontology Molecular function • copper ion binding • protein binding Cellular component • extracellular region • extracellular space • plasma membrane • membrane • platelet alpha granule lumen • extracellular vesicle Biological process • platelet degranulation • blood coagulation • blood circulation • platelet activation Sources: Amigo / QuickGO
RNA expression pattern
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	2153	14067
Ensembl	ENSG00000198734	ENSMUSG00000026579
UniProt	P12259	O88783
RefSeq (mRNA)	NM_000130	NM_007976
RefSeq (protein)	NP_000121	NP_032002
Location (UCSC)	Chr 1: 169.51 – 169.59 Mb	Chr 1: 164.15 – 164.22 Mb
PubMed search	[1]	[2]

Factor V (pronounced factor five) is a protein of the coagulation system, rarely referred to as proaccelerin or labile factor. In contrast to most other coagulation factors, it is not enzymatically active but functions as a cofactor. Deficiency leads to predisposition for hemorrhage, while some mutations (most notably factor V Leiden) predispose for thrombosis.

Genetics

The gene for factor V is located on the first chromosome (1q23). It is genomically related to the family of multicopper oxidases, and is homologous to coagulation factor VIII. The gene spans 70 kb, consists of 25 exons, and the resulting protein has a relative molecular mass of approximately 330kDa.

Physiology

Factor V synthesis occurs in the liver, principally. The molecule circulates in plasma as a single-chain molecule with a plasma half-life of 12–36 hours.

Factor V is able to bind to activated platelets and is activated by thrombin. On activation, factor V is spliced in two chains (heavy and light chain with molecular masses of 110000 and 73000, respectively) which are noncovalently bound to each other by calcium. The thereby activated factor V (now called FVa) is a cofactor of the prothrombinase complex: The activated factor X (FXa) enzyme requires calcium and activated factor V to convert prothrombin to thrombin on the cell surface membrane.

Factor Va is degraded by activated protein C, one of the principal physiological inhibitors of coagulation. In the presence of thrombomodulin, thrombin acts to decrease clotting by activating Protein C; therefore, the concentration and action of protein C are important determinants in the negative feedback loop through which thrombin limits its own activation.

Role in disease

Various hereditary disorders of factor V are known. Deficiency is associated with a rare mild form of hemophilia (termed parahemophilia or Owren parahemophilia), the incidence of which is about 1:1,000,000. It inherits in an autosomal recessive fashion.

Other mutations of factor V are associated with venous thrombosis. They are the most common hereditary causes for thrombophilia (a tendency to form blood clots). The most common one of these, factor V Leiden, is due to the replacement of an arginine residue with glutamine at amino acid position 506 (R506Q). All prothrombotic factor V mutations (factor V Leiden, factor V Cambridge, factor V Hong Kong) make it resistant to cleavage by activated protein C ("APC resistance"). It therefore remains active and increases the rate of thrombin generation.

Laboratory findings in various platelet and coagulation disorders (V - T)

Condition	Prothrombin time	Partial thromboplastin time	Bleeding time	Platelet count
Vitamin K deficiency or warfarin	Prolonged	Normal or mildly prolonged	Unaffected	Unaffected
Disseminated intravascular coagulation	Prolonged	Prolonged	Prolonged	Decreased
Von Willebrand disease	Unaffected	Prolonged or unaffected	Prolonged	Unaffected
Hemophilia	Unaffected	Prolonged	Unaffected	Unaffected
Aspirin	Unaffected	Unaffected	Prolonged	Unaffected
Thrombocytopenia	Unaffected	Unaffected	Prolonged	Decreased
Liver failure, early	Prolonged	Unaffected	Unaffected	Unaffected
Liver failure, end-stage	Prolonged	Prolonged	Prolonged	Decreased
Uremia	Unaffected	Unaffected	Prolonged	Unaffected
Congenital afibrinogenemia	Prolonged	Prolonged	Prolonged	Unaffected
Factor V deficiency	Prolonged	Prolonged	Unaffected	Unaffected
Factor X deficiency as seen in amyloid purpura	Prolonged	Prolonged	Unaffected	Unaffected
Glanzmann's thrombasthenia	Unaffected	Unaffected	Prolonged	Unaffected
Bernard-Soulier syndrome	Unaffected	Unaffected	Prolonged	Decreased or unaffected
Factor XII deficiency	Unaffected	Prolonged	Unaffected	Unaffected
C1INH deficiency	Unaffected	Shortened	Unaffected	Unaffected

History

Until the discovery of factor V, coagulation was regarded as a product of four factors: calcium (IV) and thrombokinase (III) together acting on prothrombin (II) to produce fibrinogen (I); this model had been outlined by Paul Morawitz in 1905.

The suggestion that an additional factor might exist was made by Dr Paul Owren (1905–1990), a Norwegian physician, during his investigations into the bleeding tendency of a lady called Mary (1914–2002). She had suffered from nosebleeds and menorrhagia (excessive menstrual blood loss) for most her life, and was found to have a prolonged prothrombin time, suggesting either vitamin K deficiency or chronic liver disease leading to prothrombin deficiency. However, neither were the case, and Owren demonstrated this by correcting the abnormality with plasma from which prothrombin had been removed. Using Mary's serum as index, he found that the "missing" factor, which he labeled V (I-IV having been used in Morawitz' model), had particular characteristics. Most investigations were performed during the Second World War, and while Owren published his results in Norway in 1944, he could not publish them internationally until the war was over. They appeared finally in The Lancet in 1947.

The possibility of an extra coagulation factor was initially resisted on methodological grounds by Drs Armand Quick and Walter Seegers, both world authorities in coagulation. Confirmatory studies from other groups led to their final approval several years later.

Owren initially felt that factor V (labile factor or proaccelerin) activated another factor, which he named VI. VI was the factor that accelerated the conversion from prothrombin to thrombin. It was later discovered that factor V was "converted" (activated) by thrombin itself, and later still that factor VI was simply the activated form of factor V.

The complete amino acid sequence of the protein was published in 1987. In 1994 factor V Leiden, resistant to inactivation by protein C, was described; this abnormality is the most common genetic cause for thrombosis.

Interactions

Factor V has been shown to interact with Protein S.

References

Further reading

• Nicolaes GA, Dahlbäck B (Apr 2002). "Factor V and thrombotic disease: description of a janus-faced protein". Arteriosclerosis, Thrombosis, and Vascular Biology 22 (4): 530–538. doi:10.1161/01.ATV.0000012665.51263.B7. PMID 11950687. 
• Segers K, Dahlbäck B, Nicolaes GA (Sep 2007). "Coagulation factor V and thrombophilia: background and mechanisms". Thrombosis and Haemostasis 98 (3): 530–542. doi:10.1160/th07-02-0150. PMID 17849041. 
• Hooper WC, De Staercke C (2006). "The relationship between FV Leiden and pulmonary embolism". Respiratory Research 3 (1): 8. doi:10.1186/rr180. PMC 64819. PMID 11806843. 
• Schrijver I, Houissa-Kastally R, Jones CD, Garcia KC, Zehnder JL (Feb 2002). "Novel factor V C2-domain mutation (R2074H) in two families with factor V deficiency and bleeding". Thrombosis and Haemostasis 87 (2): 294–9. PMID 11858490. 
• Mann KG, Kalafatis M (Jan 2003). "Factor V: a combination of Dr Jekyll and Mr Hyde". Blood 101 (1): 20–30. doi:10.1182/blood-2002-01-0290. PMID 12393635. 
• Duga S, Asselta R, Tenchini ML (Aug 2004). "Coagulation factor V". The International Journal of Biochemistry & Cell Biology 36 (8): 1393–9. doi:10.1016/j.biocel.2003.08.002. PMID 15147718. 
• Andreassi MG, Botto N, Maffei S (2006). "Factor V Leiden, prothrombin G20210A substitution and hormone therapy: indications for molecular screening". Clinical Chemistry and Laboratory Medicine 44 (5): 514–21. doi:10.1515/CCLM.2006.103. PMID 16681418. 
• Du X (May 2007). "Signaling and regulation of the platelet glycoprotein Ib-IX-V complex". Current Opinion in Hematology 14 (3): 262–9. doi:10.1097/MOH.0b013e3280dce51a. PMID 17414217. 

External links

• The Coagulation Factor V Protein

English Journal

• The association of idiopathic recurrent pregnancy loss with polymorphisms in hemostasis-related genes.

• Cao Y, Zhang Z, Xu J, Yuan W, Wang J, Huang X, Shen Y, Du J.SourceFudan University, 130 Dong'an Road, Shanghai 200032, China; NPFPC Laboratory of Contraception and Devices, Shanghai Institute of Planned Parenthood Research, 2140 Xietu Road, Shanghai 200032, China.
• Gene.Gene.2013 Nov 10;530(2):248-52. doi: 10.1016/j.gene.2013.07.080. Epub 2013 Aug 14.
• Recurrent pregnancy loss (RPL) is a complex, multifactorial condition. Inherited thrombophilia is the leading cause of thromboembolism and is associated with an increased risk of RPL. The aims of the current study were to investigate the effects of polymorphisms in hemostasis-related genes antithrom
• PMID 23954867

• Successful treatment of cerebral venous sinus thrombosis with the Solitaire FR thrombectomy device.

• Froehler MT.AbstractA young woman with factor V Leiden thrombophilia presented with headache due to thrombosis of the right transverse sinus (TS) and superior sagittal sinus. Despite appropriate anticoagulation, she experienced worsening headache, progressive neurologic deficits and spontaneous subarachnoid hemorrhage. Endovascular therapy was therefore undertaken. A 6 mm Solitaire FR device was deployed in the TS and withdrawn in a stepwise fashion, resulting in complete recanalization of the sinus. Her headache improved and her neurologic deficits resolved. Endovascular therapy for cerebral venous sinus thrombosis is currently recommended only for those patients with deterioration despite appropriate anticoagulation. The thrombus burden is usually high in this subset of patients, and recanalization can be challenging with currently available endovascular techniques. This is the first report of cerebral venous sinus thrombectomy with the Solitaire FR device, which may offer another option for those patients requiring endovascular treatment.
• Journal of neurointerventional surgery.J Neurointerv Surg.2013 Nov 1;5(6):e45. doi: 10.1136/neurintsurg-2012-010517. Epub 2012 Nov 7.
• A young woman with factor V Leiden thrombophilia presented with headache due to thrombosis of the right transverse sinus (TS) and superior sagittal sinus. Despite appropriate anticoagulation, she experienced worsening headache, progressive neurologic deficits and spontaneous subarachnoid hemorrhage.
• PMID 23136236

• Hypercoagulability in a newborn with concomitant homozygous factor V Leiden and severe homozygous protein C deficiency type 1.

• Al Antary ET, Haddadin IS, Hamory MK, Daauuod MM.SourceDepartment of Hematology/Oncology, Queen Rania Al-Abdullah Hospital for Children, University of Jordan, Amman, Jordan.
• Blood coagulation & fibrinolysis : an international journal in haemostasis and thrombosis.Blood Coagul Fibrinolysis.2013 Oct;24(7):777-9. doi: 10.1097/MBC.0b013e328364194b.
• This is a case report of a female newborn presented with skin necrotic lesions 1 week after delivery. Laboratory investigations revealed severe homozygous protein C deficiency associated with homozygous factor V Leiden, although her pregnancy and perinatal periods were otherwise uneventful, with neg
• PMID 24056294

Related Links

• Proaccelerin | definition of proaccelerin by Medical dictionary

proaccelerin [pro″ak-sel´er-in] factor V, one of the coagulation factors. fac·tor V in the clotting of blood, also known as: proaccelerin (Owren), labile or plasma labile factor (Quick), plasma accelerator globulin (Ware and Seegars ...

• Proaccelerin | Define Proaccelerin at Dictionary.com

Proaccelerin definition at Dictionary.com, a free online dictionary with pronunciation, synonyms and translation. Look it up now! Thesaurus Translate Puzzles & Games Word of the Day Blog Slideshows Apps by Dictionary Log Out ...

Related Pictures

---

★リンクテーブル★

リンク元	「血液凝固因子」「第V因子」

「血液凝固因子」

　　[★]

英

coagulation factor (Z), clotting factor, blood coagulation factor, blood coagulation factors

関

ビタミンK

血液凝固因子

• 第I因子
• 第II因子
• 第III因子
• 第IV因子
• 第V因子
• 第VII因子
• 第VIII因子
• 第IX因子
• 第X因子
• 第XI因子
• 第XII因子
• 第XIII因子

表

• PT.261

型	名称	同義語	分子量 (kDa)	血漿中濃度 (μg/ml)	半減期 (day)
内因系のプロ酵素	XII	Hageman因子	80	29	2
	プレカリクレイン	Fletcher因子	88	45
	XI	PTA	160	4	2.5
ビタミンK依存	VII	proconvertin	50	0.5	0.2
凝固プロ酵素	IX	Christmas因子	57	4	1
	X	Stuart因子	57	8	1.5
	II	プロトロンビン	70	150	3
補助因子	III	組織因子		0
	血小板ホスホリピド
	高分子量キニノゲン		120	70
	V	proaccelerin	330	7	1.5
	VIII	抗血友病因子			0.5
フィブリン堆積因子	I	フィブリノゲン	340	2500	4.5
	XIII	フィブリン安定因子	320	8	7
抑制物質	アンチトロンビンIII		58	150	2.5

• 標準血液病学 p.217

15種類ある

凝固因子	慣用語・同義語	ビタミンK依存	血液中半減期(hr)	産生器官	染色体座乗部位
I	fibrinogen		100-150	肝臓	4q26
II	prothronbin	○	50-80	肝臓	11p141-q12
III	tissue thromboplastin			体の各組織	1pter-p21
IV	calcium ion			肝臓
V	labile factor/proaccelerin		24	肝臓	1q21-q25
VII	stable factor/proconvertin	○	6	肝臓	13q34
VIII	antihemophilic factor		12	細網系?	xq28
IX	Christmas factor	○	24	肝臓	xq26.3-q27.2
X	Stuart factor	○	25-60	肝臓	13q34
XI	plasma thromboplastin antecedent		40-80	肝臓	4q35
XII	Hageman factor		50-70	肝臓	5q33-qter
XIII	fibrin stabilizing factor		150	肝臓	6p24-p21.3
prekallikrein	Fletcher factor		35	肝臓	4q35
hight molecular weight kininogen	Fitzgerold factor		150	肝臓	3q26-qter
von Willebrand factor			24	血管内皮 血小板 糸球体	12pter-p12

産生部位

• ほとんどが肝臓
• 例外：

• 第III因子(F III)：組織トロンボプラスチン：組織
• 第VIII因子(F VIII)：組織トロンボプラスチン：細網組織？

臨床関連

• ビタミンK欠乏
• 妊娠により第XI因子、第XIII因子を除き、血液凝固因子の濃度が上昇する

-凝固因子

「第V因子」

　　[★]

英

factor V, F V

同

プロアクセレリン proaccelerin、プラズマプロトロンビン転化因子 plasma prothrombins conversion factor PPCF、不安定因子 labile factor、促進グロブリン ACグロブリン accelerator globulin Ac-globulin、凝固第V因子、血液凝固第V因子

関

血液凝固因子