ADAMTS13 (A Disintegrin And Metalloproteinase with a ThromboSpondin type 1 motif, member 13) is a zinc-containing metalloprotease enzyme that cleaves von Willebrand factor (vWf), a large protein involved in blood clotting. It is also known as von Willebrand factor-cleaving protease (VWFCP). It is secreted in blood and degrades large vWf multimers, decreasing their activity. General Name, Symbol, Number zinc, Zn, 30 Chemical series transition metals Group, Period, Block 12, 4, d Appearance bluish pale gray Atomic mass 65. ... The metalloendopeptidases (also called metalloproteinases or metalloproteases) are a class of enzymes from the group of endopeptidases. ... Ribbon diagram of the catalytically perfect enzyme TIM. Factor D enzyme crystal prevents the immune system from inappropriately running out of control. ... Von Willebrand factor (vWF, also called Factor VIII-related antigen) is a blood protein of the coagulation system. ... The coagulation of blood is a complex process during which blood forms solid clots. ... Red blood cells (erythrocytes) are present in the blood and help carry oxygen to the rest of the cells in the body Blood is a circulating tissue composed of fluid plasma and cells (red blood cells, white blood cells, platelets). ...

Genetics

The ADAMTS13 gene is maps to the ninth chromosome (9p34). This stylistic schematic diagram shows a gene in relation to the double helix structure of DNA and to a chromosome (right). ... Figure 1: Chromosome. ...

Discovery and function

Since 1982 it had been known that thrombotic thrombocytopenic purpura (TTP), one of the microangiopathic hemolytic anemias (see below), was characterised by unusually large von Willebrand factor multimers in its familial form. It was presumed that normal blood plasma contained a proteolytic enzyme, deficiency of which caused large vWf multimers and resultant microthrombi in the small blood vessels. In 1998 IgG antibodies were discovered that caused TTP in non-familial cases. Thrombotic thrombocytopenic purpura (TTP or Moschcowitz disease) is a rare disorder of the blood coagulation system that in most cases arises from the deficiency or inhibition of the enzyme responsible for cleaving von Willebrand factor. ... In medicine (hematology) microangiopathic hemolytic anemia (MAHA) is a subgroup of hemolytic anemia (anemia, loss of red blood cells through destruction) caused by factors in the small blood vessels. ... Schematic of antibody binding to an antigen An antibody is a protein complex used by the immune system to identify and neutralize foreign objects like bacteria and viruses. ... Schematic of antibody binding to an antigen An antibody is a protein used by the immune system to identify and neutralize foreign objects like bacteria and viruses. ...

In 2001, four research groups working seperately all discovered an enzyme that cleaved ultra-large multimers of von Willebrand factor (ULVWF) between a tyrosine at position 1605 and a methionine at 1606. Tyrosine (from the Greek tyros, meaning cheese, as it was first discovered in cheese), 4-hydroxyphenylalanine, or 2-amino-3(4-hydroxyphenyl)-propanoic acid, is one of the 20 amino acids that are used by cells to synthesize proteins. ... Methionine (Met, M. C5H11NO2S) is an essential nonpolar amino acid, and a lipotropic. ...

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. Thrombospondins are secreted proteins with the ability to inhibit angiogenesis. ...

Role in disease

ADAMTS13 was originally discovered in Upshaw-Shulman syndrome, the recurring familial form of TTP. By that time it was already known that ADAMTS13 function was impaired in the autoimmune form as well, owing to its response to plasmapheresis and characterisation of IgG inhibitors. Since its discovery, specific epitopes on its surface have been shown to be the target of inhibitory antibodies. Autoimmune diseases arise from an overactive immune response of the body against substances and tissues normally present in the body. ... Plasmapheresis is the removal of (components of) blood plasma from the circulation. ... An epitope is the part of a foreign organism (or its proteins) that is being recognised by the immune system and targeted by antibodies, cytotoxic T cells or both. ...

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). Aortic valve stenosis (AS) is a heart condition caused by the incomplete opening of the aortic valve. ... In medicine (gastroenterology), angiodysplasia is a small vascular malformation of the gut. ... Shear stress is a stress state where the shape of a material tends to change (usually by sliding forces - torque by transversely-acting forces) without particular volume change. ... Heydes syndrome is a syndrome of aortic valve stenosis associated with gastrointestinal bleeding from colonic angiodysplasia. ... Hemorrhage (alternate spelling is Haemorrhage) is the medical term referring to the presence of blood in the interstitial tissues. ... Von Willebrands disease (vWD) is the most common hereditary coagulation abnormality described in humans. ...

See also

• ADAMTS5

Sources

• Levy GG, Motto DG, Ginsburg D. ADAMTS13 turns 3. Blood 2005;106:11-7. PMID 15774620.

External link

• OMIM 274150
• Secreted protein database entry