ADAMTS13 (adisintegrin andmetalloproteinase with a thrombospondin type 1 motif, member 13)—also known as von Willebrand factor-cleaving protease (VWFCP)—is a zinc-containing metalloproteaseenzyme that cleaves von Willebrand factor (vWf), a large protein involved in blood clotting. It is secreted into the blood and degrades large vWf multimers, decreasing their activity, hence ADAMTS13 acts to reduce thrombus formation.[5]
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 plateletmicrothrombi in the small blood vessels. In addition, they reported that IgGantibodies directed against this same enzyme caused TTP in a majority of non-familial cases.[5]
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 is not anchored in the cell membrane.[5]
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.[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.
López JA, Dong JF (January 2004). "Cleavage of von Willebrand factor by ADAMTS-13 on endothelial cells". Seminars in Hematology. 41 (1): 15–23. doi:10.1053/j.seminhematol.2003.10.004. PMID14727255.
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.
Schneppenheim R, Budde U, Hassenpflug W, Obser T (January 2004). "Severe ADAMTS-13 deficiency in childhood". Seminars in Hematology. 41 (1): 83–9. doi:10.1053/j.seminhematol.2003.10.007. PMID14727263.
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 the PDB for UniProt: Q76LX8 (A disintegrin and metalloproteinase with thrombospondin motifs 13) at the PDBe-KB.
