ADAMTS13 (adisintegrinandmetalloproteinase with athrombospondin type 1 motif, member13)—also known asvon Willebrand factor-cleaving protease (VWFCP)—is azinc-containingmetalloproteaseenzyme that cleavesvon Willebrand factor (vWf), a large protein involved inblood clotting. It is secreted into theblood and degrades large vWf multimers, decreasing their activity, henceADAMTS13 acts to reduce thrombus formation.[5]
In 1994, vWF was shown to be cleaved between atyrosine at position 1605 and amethionine 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-cleavingprotease was associated with formation ofplateletmicrothrombi in the small blood vessels. In addition, they reported thatIgGantibodies directed against this same enzyme caused TTP in a majority of non-familial cases.[5]
Genomically, ADAMTS13 shares many properties with the 19 memberADAMTS family, all of which are characterised by a protease domain (the part that performs the protein hydrolysis), an adjacentdisintegrin domain and one or morethrombospondin domains. ADAMTS13 in fact has eight thrombospondin domains. It has no hydrophobic transmembrane domain, and hence it is not anchored in the cell membrane.[5]
Deficiency of ADAMTS13 was originally discovered inUpshaw Schulman Syndrome, the recurring familial form ofthrombotic thrombocytopenic purpura. By that time it was already suspected that TTP occurred in theautoimmune form as well, owing to its response toplasmapheresis and characterisation of IgG inhibitors. Since the discovery of ADAMTS13, specificepitopes on its surface have been shown to be the target of inhibitory antibodies.[5][6][7]
Low levels of ADAMTS13 are also associated with an increased risk of arterial thrombosis,[8] including myocardial infarction[9] and cerebrovascular disease.[10][11]
^Furlan M, Lämmle B (June 2001). "Aetiology and pathogenesis of thrombotic thrombocytopenic purpura and haemolytic uraemic syndrome: the role of von Willebrand factor-cleaving protease".Best Practice & Research. Clinical Haematology.14 (2):437–54.doi:10.1053/beha.2001.0142.PMID11686108.
^Sonneveld MA, de Maat MP, Leebeek FW (July 2014). "Von Willebrand factor and ADAMTS13 in arterial thrombosis: a systematic review and meta-analysis".Blood Reviews.28 (4):167–78.doi:10.1016/j.blre.2014.04.003.PMID24825749.
Tang BL (January 2001). "ADAMTS: a novel family of extracellular matrix proteases".The International Journal of Biochemistry & Cell Biology.33 (1):33–44.doi:10.1016/S1357-2725(00)00061-3.PMID11167130.
Fujimura Y, Matsumoto M, Yagi H, Yoshioka A, Matsui T, Titani K (January 2002). "Von Willebrand factor-cleaving protease and Upshaw-Schulman syndrome".International Journal of Hematology.75 (1):25–34.doi:10.1007/BF02981975.PMID11843286.S2CID19926816.
Plaimauer B, Scheiflinger F (January 2004). "Expression and characterization of recombinant human ADAMTS-13".Seminars in Hematology.41 (1):24–33.doi:10.1053/j.seminhematol.2003.10.006.PMID14727256.
Kokame K, Miyata T (January 2004). "Genetic defects leading to hereditary thrombotic thrombocytopenic purpura".Seminars in Hematology.41 (1):34–40.doi:10.1053/j.seminhematol.2003.10.002.PMID14727257.
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 (September 2007). "Serial changes in von Willebrand factor-cleaving protease (ADAMTS13) and prognosis after acute myocardial infarction".The American Journal of Cardiology.100 (5):758–63.doi:10.1016/j.amjcard.2007.03.095.PMID17719316.
Overview of all the structural information available in thePDB forUniProt:Q76LX8 (A disintegrin and metalloproteinase with thrombospondin motifs 13) at thePDBe-KB.
