Recombinant Human ADAMTS13 Protein, CF

ADAMTS13 (a disintegrin and metalloproteinase with thrombospondin motifs 13), also known as von Willebrand Factor (vWF) cleaving protease, is a member of the family of secreted zinc proteases with a multi-domain structure (1‑3). The protein precursors consist of a signal peptide and following domains: pro, catalytic, disintegrin-like, TS type 1 motif, cysteine-rich, spacer, a second set of seven TSP1 repeats, and two CUB domins. The only known substrate of ADAMTS13 is vWF, a blood glycoprotein with two homeostatic functions (4). It is required for platelet adhesion to sites of vascular damage and acts as a carrier protein for blood-clotting factor VIII in the circulation. It exists in plasma as multimers, the largest of which effectively mediate platelet adhesion. ADAMTS13 cleaves multimeric vWF in the A2 domain at the position, Tyr1605‑Met1606. A defect in ADAMTS13 activity is a cause of congenital thrombotic thrombocytopenic purpura (TTP), also known as Upshaw‑Schulman syndrome. Lack of ADAMTS13 activity allows unusually large vWF (UlvWF) to occur in plasma (5). These UlvWF multimers have tendency to agglutinate circulating platelets at sites with high levels of shear stress to cause TTP. The purified rhADAMTS13 ends in the spacer domain. The rhvWF‑A2 cleaving activity of rhADAMTS13 can be inhibited by 5 mM 1,10-phenanthroline.