ADAMTS13

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

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

Discovery
Since 1982 it had been known that is_associated_with::thrombotic thrombocytopenic purpura (TTP), one of the is_associated_with::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 is_associated_with::tyrosine at position 1605 and a is_associated_with::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 is_associated_with::protease was associated with formation of is_associated_with::platelet microthrombi in the small blood vessels. In addition, they reported that is_associated_with::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 is_associated_with::disintegrin domain and one or more is_associated_with::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 is_associated_with::Upshaw Schulman Syndrome, the recurring familial form of is_associated_with::thrombotic thrombocytopenic purpura. By that time it was already suspected that TTP occurred in the is_associated_with::autoimmune form as well, owing to its response to is_associated_with::plasmapheresis and characterisation of IgG inhibitors. Since the discovery of ADAMTS13, specific is_associated_with::epitopes on its surface have been shown to be the target of inhibitory antibodies.

Especially since the link between is_associated_with::aortic valve stenosis and is_associated_with::angiodysplasia was proven to be due to high is_associated_with::shear stress (is_associated_with::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 is_associated_with::von Willebrand disease (type 2a).