ADAMTS13

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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2015/08/05 18:46:45」(JST)

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ADAM metallopeptidase with thrombospondin type 1 motif, 13
Rendering based on PDB 3GHM.
Available structures PDB Ortholog search: PDBe, RCSB List of PDB id codes 3GHM, 3GHN, 3VN4
Identifiers
Symbols	ADAMTS13 ; ADAM-TS13; ADAMTS-13; C9orf8; VWFCP; vWF-CP
External IDs	OMIM: 604134 MGI: 2685556 HomoloGene: 16372 GeneCards: ADAMTS13 Gene
EC number	3.4.24.87
Gene ontology Molecular function • metalloendopeptidase activity • integrin binding • calcium ion binding • protein binding • metallopeptidase activity • zinc ion binding Cellular component • proteinaceous extracellular matrix • extracellular space • endoplasmic reticulum lumen • cell surface Biological process • protein O-linked glycosylation • proteolysis • cell-matrix adhesion • integrin-mediated signaling pathway • glycoprotein metabolic process • response to toxic substance • protein processing • platelet activation • response to interferon-gamma • response to tumor necrosis factor • protein O-linked fucosylation • peptide catabolic process • post-translational protein modification • cellular protein metabolic process • response to interleukin-4 Sources: Amigo / QuickGO
RNA expression pattern
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	11093	279028
Ensembl	ENSG00000160323	ENSMUSG00000014852
UniProt	Q76LX8	Q769J6
RefSeq (mRNA)	NM_139025	NM_001001322
RefSeq (protein)	NP_620594	NP_001001322
Location (UCSC)	Chr 9: 133.41 – 133.46 Mb	Chr 2: 26.97 – 27.01 Mb
PubMed search	[1]	[2]

ADAMTS13 (a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13)—also known as von Willebrand factor-cleaving protease (VWFCP)—is a zinc-containing metalloprotease enzyme that cleaves von Willebrand factor (vWf), a large protein involved in blood clotting. It is secreted in blood and degrades large vWf multimers, decreasing their activity.

Genetics

The ADAMTS13 gene maps to the ninth chromosome (9q34).

Discovery

Since 1982 it had been known that thrombotic thrombocytopenic purpura (TTP), one of the microangiopathic hemolytic anemias (see below), was characterized in its familial form by the presence in plasma of unusually large von Willebrand factor multimers (ULVWF).

In 1994, vWF was shown to be cleaved between a tyrosine at position 1605 and a methionine at 1606 by a plasma metalloprotease enzyme when it was exposed to high levels of shear stress. In 1996, two research groups independently further characterized this enzyme. In the next two years, the same two groups showed that the congenital deficiency of a vWF-cleaving protease was associated with formation of platelet microthrombi in the small blood vessels. In addition, they reported that IgG antibodies directed against this same enzyme caused TTP in a majority of non-familial cases.

Proteomics

Genomically, ADAMTS13 shares many properties with the 19 member ADAMTS family, all of which are characterised by a protease domain (the part that performs the protein hydrolysis), an adjacent disintegrin domain and one or more thrombospondin domains. ADAMTS13 in fact has eight thrombospondin domains. It has no hydrophobic transmembrane domain, and hence it not anchored in the cell membrane.

Role in disease

Deficiency of ADAMTS13 was originally discovered in Upshaw Schulman Syndrome, the recurring familial form of thrombotic thrombocytopenic purpura. By that time it was already suspected that TTP occurred in the autoimmune form as well, owing to its response to plasmapheresis and characterisation of IgG inhibitors. Since the discovery of ADAMTS13, specific epitopes on its surface have been shown to be the target of inhibitory antibodies.

Especially since the link between aortic valve stenosis and angiodysplasia was proven to be due to high shear stress (Heyde's syndrome), it has been accepted that increased exposure of vWf to ADAMTS13 due to various reasons would predispose to bleeding by causing increased degradation of vWf. This phenomenon is characterised by a form of von Willebrand disease (type 2a).

See also

• ADAMTS5

References

Further reading

• Furlan M, Lammle B. Aetiology and pathogenesis of thrombotic thrombocytopenic purpura and haemolytic uraemic syndrome: the role of von Willebrand factor-cleaving protease. Best Pract Res Clin Haematol 2001;14:437-54. PMID 11686108.
• Tsai HM. Advances in the pathogenesis, diagnosis, and treatment of thrombotic thrombocytopenic purpura. J Am Soc Nephrol 2003;14:1072-81. PMID 12660343.
• Tang BL (2001). "ADAMTS: a novel family of extracellular matrix proteases.". Int. J. Biochem. Cell Biol. 33 (1): 33–44. doi:10.1016/S1357-2725(00)00061-3. PMID 11167130. 
• Fujimura Y, Matsumoto M, Yagi H et al. (2002). "Von Willebrand factor-cleaving protease and Upshaw-Schulman syndrome.". Int. J. Hematol. 75 (1): 25–34. doi:10.1007/BF02981975. PMID 11843286. 
• Zheng X, Majerus EM, Sadler JE (2003). "ADAMTS13 and TTP.". Curr. Opin. Hematol. 9 (5): 389–94. doi:10.1097/00062752-200209000-00001. PMID 12172456. 
• Tsai HM (2003). "Von Willebrand factor, ADAMTS13, and thrombotic thrombocytopenic purpura.". J. Mol. Med. 80 (10): 639–47. doi:10.1007/s00109-002-0369-8. PMID 12395148. 
• Tsai HM (2003). "Platelet activation and the formation of the platelet plug: deficiency of ADAMTS13 causes thrombotic thrombocytopenic purpura.". Arterioscler. Thromb. Vasc. Biol. 23 (3): 388–96. doi:10.1161/01.ATV.0000058401.34021.D4. PMID 12615692. 
• Tsai HM (2003). "Is severe deficiency of ADAMTS-13 specific for thrombotic thrombocytopenic purpura? Yes.". J. Thromb. Haemost. 1 (4): 625–31. doi:10.1046/j.1538-7836.2003.00169.x. PMID 12871390. 
• Remuzzi G (2003). "Is ADAMTS-13 deficiency specific for thrombotic thrombocytopenic purpura? No.". J. Thromb. Haemost. 1 (4): 632–4. doi:10.1046/j.1538-7836.2003.00170.x. PMID 12871391. 
• Moake JL (2004). "von Willebrand factor, ADAMTS-13, and thrombotic thrombocytopenic purpura.". Semin. Hematol. 41 (1): 4–14. doi:10.1053/j.seminhematol.2003.10.003. PMID 14727254. 
• López JA, Dong JF (2004). "Cleavage of von Willebrand factor by ADAMTS-13 on endothelial cells.". Semin. Hematol. 41 (1): 15–23. doi:10.1053/j.seminhematol.2003.10.004. PMID 14727255. 
• Plaimauer B, Scheiflinger F (2004). "Expression and characterization of recombinant human ADAMTS-13.". Semin. Hematol. 41 (1): 24–33. doi:10.1053/j.seminhematol.2003.10.006. PMID 14727256. 
• Kokame K, Miyata T (2004). "Genetic defects leading to hereditary thrombotic thrombocytopenic purpura.". Semin. Hematol. 41 (1): 34–40. doi:10.1053/j.seminhematol.2003.10.002. PMID 14727257. 
• Schneppenheim R, Budde U, Hassenpflug W, Obser T (2004). "Severe ADAMTS-13 deficiency in childhood.". Semin. Hematol. 41 (1): 83–9. doi:10.1053/j.seminhematol.2003.10.007. PMID 14727263. 
• Kremer Hovinga JA, Studt JD, Lämmle B (2005). "The von Willebrand factor-cleaving protease (ADAMTS-13) and the diagnosis of thrombotic thrombocytopenic purpura (TTP).". Pathophysiol. Haemost. Thromb. 33 (5-6): 417–21. doi:10.1159/000083839. PMID 15692254. 
• Levy GG, Motto DG, Ginsburg D (2005). "ADAMTS13 turns 3.". Blood 106 (1): 11–7. doi:10.1182/blood-2004-10-4097. PMID 15774620. 
• George JN (2005). "ADAMTS13, thrombotic thrombocytopenic purpura, and hemolytic uremic syndrome.". Curr. Hematol. Rep. 4 (3): 167–9. PMID 15865866. 
• Dong JF (2005). "Cleavage of ultra-large von Willebrand factor by ADAMTS-13 under flow conditions.". J. Thromb. Haemost. 3 (8): 1710–6. doi:10.1111/j.1538-7836.2005.01360.x. PMID 16102037. 
• Matsukawa, M.; Kaikita, K.; Soejima, K.; Fuchigami, S.; Nakamura, Y.; Honda, T.; Tsujita, K.; Nagayoshi, Y.; Kojima, S.; Shimomura, H.; Sugiyama, S.; Fujimoto, K.; Yoshimura, M.; Nakagaki, T.; Ogawa, H. (2007). "Serial Changes in von Willebrand Factor-Cleaving Protease (ADAMTS13) and Prognosis After Acute Myocardial Infarction". The American Journal of Cardiology 100 (5): 758–763. doi:10.1016/j.amjcard.2007.03.095. PMID 17719316. 

External links

• The MEROPS online database for peptidases and their inhibitors: M12.241

External links

• Online 'Mendelian Inheritance in Man' (OMIM) 274150
• Secreted protein database entry

UpToDate Contents

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• 1. Pathophysiology of acquired TTP and other primary thrombotic microangiopathies (TMAs)
• 2. 後天性TTP：臨床症状および診断 acquired ttp clinical manifestations and diagnosis
• 3. 溶血性尿毒症症候群（HUS）、血栓性血小板減少性紫斑病（TTP）、またはその他の血栓性微小血管障害症（TMA）が疑われる患者に対するアプローチ approach to the patient with suspected ttp hus or other thrombotic microangiopathy tma
• 4. 後天性TTP：急性発症からの回復後および寛解中のマネージメント acquired ttp management following recovery from an acute episode and during remission
• 5. von Willebrand因子の生物学および正常機能 biology and normal function of von willebrand factor

English Journal

• Idiopathic Noncirrhotic Intrahepatic Portal Hypertension is Associated with Sustained ADAMTS13 Deficiency.

• Mackie I, Eapen CE, Neil D, Lawrie AS, Chitolie A, Shaw JC, Elias E.SourceHaemostasis Research Unit, Haematology Department, University College London, London, UK, i.mackie@ucl.ac.uk.
• Digestive diseases and sciences.Dig Dis Sci.2011 Aug;56(8):2456-65. Epub 2011 May 15.
• BACKGROUND: ADAMTS13 deficiency leading to excess ultralarge von Willebrand factor (VWF) multimers and platelet clumping is typically found in thrombotic thrombocytopenic purpura (a type of thrombotic microangiopathy). Idiopathic noncirrhotic intrahepatic portal hypertension (NCIPH) is a microangiop
• PMID 21573942

Japanese Journal

• 溶血性尿毒症症候群,血栓性血小板減少性紫斑病 (特集 腎障害をきたす全身性疾患--最近の進歩)

• 藤村 吉博,松本 雅則,八木 秀男
• 日本内科学会雑誌 100(5), 1296-1307, 2011-05-10
• NAID 40018861479

Related Links

• 難病情報センター | 血栓性血小板減少性紫斑病（TTP）

1)ADAMTS13活性の先天性欠損、2)後天性にADAMTS13に対する自己抗体（IgG型 中和抗体、IgA、IgM型非中和抗体）の ... 先天性TTPの USSは第９染色体上にある ADAMTS13遺伝子の異常に基づく病気で、遺伝形式は見かけ上常染色体劣性を示し ます。

• ADAMTS13 - Wikipedia, the free encyclopedia

ADAMTS13 (a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13)—also known as von Willebrand factor-cleaving protease ( VWFCP)—is a zinc-containing metalloprotease enzyme that cleaves von Willebrand ...

Related Pictures

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★リンクテーブル★

リンク元	「血栓性血小板減少性紫斑病」

「血栓性血小板減少性紫斑病」

　　[★]

英

thrombotic thrombocytopenic purpura, TTP

同

モシュコビッツ症候群 モシュコウィッツ病 Moschkowitz's syndrome Moschcowitz disease

関

溶血性尿毒症症候群 hemolytic uremic syndrome HUS、血小板減少、難病

同

TTP

• ICU.594やuptodate([1] [2])も参考になった

病型

• 先天性：VWF-CPの遺伝子異常
• 後天性

• 特発性：VWF-CP に対する自己抗体産生
• 二次性：自己免疫疾患、薬物(チクロピジン)、妊娠などによる自己抗体の出現

病因

• vWF切断酵素(ADAMTS13)活性の低下

• 1. 先天的な酵素活性の低下
• 2. vWF切断酵素に対する自己抗体

病態

IMD.985 YN.G-83

• vWF切断酵素(ADAMTS13)活性の低下　→　unusually large vWFマルチマーが分解されない　→　血小板凝固促進

• 1. 血小板消費　→　出血傾向
• 2. 微小血管血小板血栓

• 2-1. 循環障害　→　腎臓(腎不全)、脳の障害(精神症状)
• 2-2. 狭窄血管の中への赤血球循環　→　破砕赤血球(MAHA)　→　溶血性貧血

• 発熱：組織崩壊、溶血、発熱中枢障害による

TTPの5徴候

let's memorize: The Fr.(=The franch)

• 血小板減少 thrombocytopenia
• 細血管障害性溶血性貧血（microangiopathic hemolytic anemia MAHA）
• 動揺する精神神経症状 encephalopathy
• 発熱 fever
• 腎障害 renal dysfunction

(⇔溶血性尿毒症症候群 HUS は血小板減少、細血管障害性溶血性貧血、腎障害。精神症状と発熱は特徴的ではない)

鑑別診断

• 血小板減少：膠原病(SLEなど)、抗リン脂質抗体症候群、特発性血小板減少症 ITP、肝硬変、骨髄異形成症候群 MDS、播種性血管内凝固症候群(DIC)

治療

• 血漿交換療法

• 奏功するはっきりとしたメカニズムは不明だが、異常なvWF重合体、血小板活性化因子 PAF、あるいは免疫複合体除去、ULvWF重合体やプロスタサイクリンの置換(血漿交換で血漿内に入れる)によるものと考えられている(WCH.1559)

• 血漿輸注療法　→　先天性のTTPの場合
• 抗血小板薬
• 副腎皮質ステロイド

• 血小板輸血は原則禁忌：血小板輸血の間に腎機能や神経学的状態(neurologic status)が著明に悪化するため(WCH.1559)

USMLE

• Q book p.290 14

予後

• 寛解後した患者の1/3が初期再発(完全寛解後1ヶ月間)、あるいは後期再発(late relapse)(最初のエピソードから10年以内)する。

参考

• 難病情報センター

http://www.nanbyou.or.jp/sikkan/026_i.htm