Enhanced cleavage of VWF variant by ADAMTS13

Under normal physiological conditions, a disintegrin and metalloproteinase with thrombospondin type 1 repeats 13 (ADAMTS13) downregulates von Willebrand factor (VWF) procoagulant activity by cleaving the peptide bond between Tyr1605 and Met1606 of VWF in a shear-dependent manner. This Reactome event describes von Willebrand disease (VWD)-associated missense mutations VWF Y1584C (Bowen DJ et al., 2005; Keeney S et al., 2007; Pruss CM et al., 2012), I1568N, G1579R, G1631D, and C1099P (Jacobi PM et al., 2012), which showed enhanced susceptibility to ADAMTS13-mediated proteolysis.

在正常生理状态下，解聚素和金属蛋白酶具有血栓素蛋白1型重复序列13（ADAMTS13）通过剪切依赖性方式切割血管性血友病因子（VWF）中酪氨酸1605和甲硫氨酸1606之间的肽键，从而下调VWF的促凝活性。本Reactome事件描述了与血管性血友病（VWD）相关的错义突变VWF Y1584C（Bowen DJ 等，2005；Keeney S 等，2007；Pruss CM 等，2012）、I1568N、G1579R、G1631D 和 C1099P（Jacobi PM 等，2012），这些突变表现出对ADAMTS13介导的蛋白水解作用的增强敏感性。