FVIIIa 变体辅因子功能缺陷
中文名称
通路描述
激活状态的因子 VIII (FVIIIa) 作为辅因子与丝氨酸蛋白酶 FIXa 结合，将前体酶 FX 转化为活性酶 FXa。FVIII 的 S577-Q584 区域内的错义突变与轻度/中度 HA 相关 (Amano K 等人，1998; Celie PH 等人，1999; Jenkins PV 等人，2002)。功能测定显示，突变 S577F, V578A, D579A 和 Q584R 干扰 FVIIIa:FIXa 介导的 FX 激活，因此这些突变的效果是降低 FVIII 在 FXa 生成中的辅因子潜力。Reactome 事件描述了因 FIXa 与 HA 相关 FVIIIa 变体相互作用导致的 FXa 生成失败，这是由于缺陷 FVIII 作为 FIXa 辅因子的能力降低所致。
英文描述
Defective cofactor function of FVIIIa variant Factor VIII (FVIII) in its activated form, FVIIIa, acts as a cofactor to the serine protease FIXa, in the conversion of the zymogen FX to the active enzyme (FXa). Missense mutations within the S577-Q584 region of FVIII have been associated with mild/moderate hemophilia A (HA) (Amano K et al. 1998; Celie PH et al. 1999; Jenkins PV et al. 2002). A functional assay demonstrated that the mutations S577F, V578A, D579A, and Q584R interfere with FVIIIa:FIXa-mediated stimulation of FX activation thus the effect of the mutations is to reduce the cofactor potential of FVIII in FXa generation. The Reactome event describes failed generation of FXa as the functional consequence of the FIXa interaction with HA-associated FVIIIa variants due to reduced ability of defective FVIII to act as a cofactor for FIXa within the intrinsic tenase complex.
所含基因
3 个基因