ADAMTS13

ADAMTS13
已知的结构
PDB	直系同源搜索: PDBe RCSB
PDBID列表
	3GHM、3GHN
识别号
别名	ADAMTS13；, ADAM-TS13, ADAMTS-13, C9orf8, VWFCP, vWF-CP, ADAM metallopeptidase with thrombospondin type 1 motif 13
外部ID	OMIM：604134 MGI：2685556 HomoloGene：16372 GeneCards：ADAMTS13
相关疾病
	Upshaw-Schulman综合症
基因位置（人类）
染色体	9号染色体
终止	133,459,402 bp
基因位置（小鼠）
染色体	小鼠2号染色体
终止	26,899,640 bp
RNA表达模式
	查阅更多表达数据
基因本体
分子功能	• calcium ion binding; • endopeptidase activity; • 金属离子结合; • integrin binding; • 肽酶活性; • 血浆蛋白结合; • metalloendopeptidase activity; • 水解酶活性; • metallopeptidase activity; • 锌离子结合;
细胞组分	• endoplasmic reticulum lumen; • 细胞外区域; • cell surface; • 细胞外空间; • 细胞外间质;
生物学过程	• 止血; • glycoprotein metabolic process; • response to interleukin-4; • response to interferon-gamma; • protein processing; • 凝血; • 蛋白酶解; • platelet activation; • response to tumor necrosis factor; • integrin-mediated signaling pathway; • cell-matrix adhesion; • response to toxic substance; • peptide catabolic process; • response to potassium ion; • cellular response to interferon-gamma; • cellular response to lipopolysaccharide; • response to amine; • cellular response to interleukin-4; • cellular response to tumor necrosis factor;
	Sources:Amigo / QuickGO
直系同源
	11093
	279028
	ENSG00000160323; ENSG00000281244
	ENSMUSG00000014852
	Q76LX8
	Q769J6
	NM_139025; NM_139026; NM_139027; NM_139028
	NM_001001322; NM_001290463; NM_001290464; NM_001290465
	NP_620594; NP_620595; NP_620596
	NP_001001322; NP_001277392; NP_001277393; NP_001277394
	维基数据
查看/编辑人类	查看/编辑小鼠

ADAMTS13（a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13），又称温韦伯氏因子裂合酶（von Willebrand factor-cleaving protease，VWFCP）是一种含锌的金属蛋白酶。ADAMTS13可以裂解一种称为温韦伯氏因子（英语：von Willebrand factor）（vWf）的大型凝血因子。为一种主要由肝脏星状细胞(stellate cell)制造的蛋白酶，少量由血管内皮细胞、血小板、肾脏足细胞及肾小管上皮细胞分泌^[6]，在人体与动物实验中皆发现受试者接受部分肝切除手术后，ADAMTS13的活性会下降至正常值的30~40%，可见肝脏对ADAMTS13的制造具有重要的贡献。本酵素存在于血液之中，降解vWf多聚体，以降低它们的活性^[7]。

遗传学

ADAMTS13基因存在于第九对染色体（9q34）上^[7]。

发现

自1982年时，人们就知道遗传性血栓性血小板减少性紫癜（英语：thrombotic thrombocytopenic purpura）（TTP，一种微血管病性溶血性贫血（英语：microangiopathic hemolytic anemia））患者的血浆中，存在异常巨大的温韦伯氏因子多聚体（ULVWF）^[7]。

1994年，发现在高剪力下时，有一种血浆金属酶会从vWF第1605位的酪氨酸及1606位的甲硫氨酸间切割。1996年，两个独立研究团队分别发现该酵素。自接下来的两年，同样的两个团队证明了vWF裂合酶与小血管的血小板血栓生成相关。此外他们还报导了在大部分非遗传性TTP患者身上，能发现对抗ADAMTS13的IgG 抗体^[7]。

蛋白质组学

ADAMTS家族（英语：ADAMTS）目前共已知有19种蛋白质，ADAMTS13属于其中一员，与其他金属蛋白酶族同样有一个14个相异的结构域组成的结构，包括金属蛋白酶(metalloprotease)、解整合素(disintegrin)、TSP1(first thrombospondin type 1 repeat)和间隔域(spacer domain) ，但ADAMTS13并不具备穿膜蛋白结构，因此其不存在细胞膜上，而是随着血液循环在大小血管内作用。该家族的蛋白质拥有蛋白酶结构域，可以水解蛋白质，邻近则有解聚素（英语：disintegrin）结构域，且含有多个血小板反应蛋白（英语：thrombospondin）结构域。ADAMTS13含有8个血小板反应蛋白结构域，且无输水穿膜段，所以该蛋白并非膜蛋白^[7]。

临床角色

ADAMTS13缺乏症最早发现于Upshaw Schulman Syndrome（英语：Upshaw Schulman Syndrome），为一种复发性遗传性血栓性血小板减少性紫癜（英语：thrombotic thrombocytopenic purpura）。当时学界认为该病属于一种自身免疫疾病，因为该疾病使用血浆置换及IgG抑制剂。在ADAMTS13发现后，研究人员发现这些自身抗体会对抗该蛋白上的抗原表位^[7]^[8]^[9]。ADAMTS13具有裂解温韦伯氏因子多聚体(UL-VWFM)并降低温韦伯氏因子活性的功能，能抑止血小板堆积于微血管形成血栓。^[10]由血管内皮细胞分泌的ADAMTS13，可能负责大部分新生温韦伯氏因子多聚体的裂解，以达到即刻性抑止血栓形成的作用。当ADAMTS13受到自身抗体的攻击而导致活性下降(小于正常活性10%)，即可能造成呈现巨分子状态的温韦伯氏因子(也就是温韦伯氏因子多聚体)沉积后黏附于血管内皮细胞表层，促使微小血管中血小板凝集，使血液中游离的血小板数量不足，同时血管中的纤维蛋白增加亦破坏红细胞结构，形成不正常型态的血细胞 (例如:裂细胞Schistocyte)与发生溶血现象，导致产生获得性血栓性血小板减少性紫斑症的临床症状。

   研究中發現ADAMTS13低下除了與獲得性血栓性血小板減少性紫斑症的形成密切相關外，在其他栓塞性微血管病變(thrombotic microangiopathy,TMA)中ADAMTS13有不同程度的下降^[11] ，在敗血症、惡性高血壓病患及自體免疫患者中也有發生相似的變化^[12]^[13] ，因此合理的推論ADAMTS13活性下降雖然不一定成為直接造成上述疾病的成因，但極有可能在這些病症中擔任促成因子的角色。

参见

ADAMTS5（英语：ADAMTS5）

参考文献

^ 與ADAMTS13相關的疾病；在維基數據上查看/編輯參考.
^ ^2.0 ^2.1 ^2.2 GRCh38: Ensembl release 89: ENSG00000160323、ENSG00000281244 - Ensembl, May 2017
^ ^3.0 ^3.1 ^3.2 GRCm38: Ensembl release 89: ENSMUSG00000014852 - Ensembl, May 2017
^ Human PubMed Reference:. National Center for Biotechnology Information, U.S. National Library of Medicine.
^ Mouse PubMed Reference:. National Center for Biotechnology Information, U.S. National Library of Medicine.
^ [Turner N, Nolasco L, Tao Z, et al. Human endothelial cells synthesize and release ADAMTS-13. J Thromb Haemost. 2006;4:1396–1404.]
^ ^7.0 ^7.1 ^7.2 ^7.3 ^7.4 ^7.5 Levy GG, Motto DG, Ginsburg D. ADAMTS13 turns 3. Blood. 2005, 106 (1): 11–7 [2016-12-20]. PMID 15774620. doi:10.1182/blood-2004-10-4097. （原始内容存档于2010-08-24）.
^ Tsai HM. Advances in the pathogenesis, diagnosis, and treatment of thrombotic thrombocytopenic purpura. J. Am. Soc. Nephrol. 2003, 14 (4): 1072–81 [2016-12-20]. PMID 12660343. doi:10.1097/01.ASN.0000060805.04118.4C. （原始内容存档于2007-10-20）.
^ Furlan M, Lämmle 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 (2): 437–54. PMID 11686108. doi:10.1053/beha.2001.0142.
^ [Levy GG, Motto DG, Ginsburg D. ADAMTS13 turns 3. Blood. 2005, 106 (1): 11–7]
^ [Martin K, Borgel D, Lerolle N, et al. Decreased ADAMTS-13 (A disintegrin-like and metalloprotease with thrombospondin type 1 repeats) is associated with a poor prognosis in sepsis-induced organ failure. Crit Care Med. 2007;35(10):2375-2382.]
^ [Farkas P, Csuka D, Mikes B, et al. Complement activation, inflammation and relative ADAMTS13 deficiency in secondary thrombotic microangiopathies. Immunobiology. 2017;222(2):119-127.]
^ [Khanal N, Dahal S, Upadhyay S, Bhatt VR, Bierman PJ. Differentiating malignant hypertension-induced thrombotic microangiopathy from thrombotic thrombocytopenic purpura. Ther Adv Hematol. 2015;6(3):97-102..]

延伸阅读

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

外部链接

The MEROPS online database for peptidases and their inhibitors: M12.241^{[失效链接]}
OMIM 274150
Secreted protein database entry
Human ADAMTS13 genome location and ADAMTS13 gene details page in the UCSC Genome Browser（英语：UCSC Genome Browser）.

Category:ADAMTS（英语：Category:ADAMTS）

[1] 與ADAMTS13相關的疾病；在維基數據上查看/編輯參考.

[refGRCh38Ensembl-2] 2.0 ^2.1 ^2.2 GRCh38: Ensembl release 89: ENSG00000160323、ENSG00000281244 - Ensembl, May 2017

[refGRCm38Ensembl-3] 3.0 ^3.1 ^3.2 GRCm38: Ensembl release 89: ENSMUSG00000014852 - Ensembl, May 2017

[4] Human PubMed Reference:. National Center for Biotechnology Information, U.S. National Library of Medicine.

[5] Mouse PubMed Reference:. National Center for Biotechnology Information, U.S. National Library of Medicine.

[6] [Turner N, Nolasco L, Tao Z, et al. Human endothelial cells synthesize and release ADAMTS-13. J Thromb Haemost. 2006;4:1396–1404.]

[Levy2005-7] 7.0 ^7.1 ^7.2 ^7.3 ^7.4 ^7.5 Levy GG, Motto DG, Ginsburg D. ADAMTS13 turns 3. Blood. 2005, 106 (1): 11–7 [2016-12-20]. PMID 15774620. doi:10.1182/blood-2004-10-4097. （原始内容存档于2010-08-24）.

[8] Tsai HM. Advances in the pathogenesis, diagnosis, and treatment of thrombotic thrombocytopenic purpura. J. Am. Soc. Nephrol. 2003, 14 (4): 1072–81 [2016-12-20]. PMID 12660343. doi:10.1097/01.ASN.0000060805.04118.4C. （原始内容存档于2007-10-20）.

[9] Furlan M, Lämmle 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 (2): 437–54. PMID 11686108. doi:10.1053/beha.2001.0142.

[10] [Levy GG, Motto DG, Ginsburg D. ADAMTS13 turns 3. Blood. 2005, 106 (1): 11–7]

[11] [Martin K, Borgel D, Lerolle N, et al. Decreased ADAMTS-13 (A disintegrin-like and metalloprotease with thrombospondin type 1 repeats) is associated with a poor prognosis in sepsis-induced organ failure. Crit Care Med. 2007;35(10):2375-2382.]

[12] [Farkas P, Csuka D, Mikes B, et al. Complement activation, inflammation and relative ADAMTS13 deficiency in secondary thrombotic microangiopathies. Immunobiology. 2017;222(2):119-127.]

[13] [Khanal N, Dahal S, Upadhyay S, Bhatt VR, Bierman PJ. Differentiating malignant hypertension-induced thrombotic microangiopathy from thrombotic thrombocytopenic purpura. Ther Adv Hematol. 2015;6(3):97-102..]

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