缺陷F9激活
中文名称
通路描述
FIX缺乏或功能障碍导致血友病B（HB），这是一种X连锁隐性出血障碍。在分子水平上，HB是由于F9基因中广泛存在的异质谱系突变引起的（Rallapalli PM等，2013）。Reactome事件描述了因FIX变体中血友病B相关点突变R191C、R191H、R226Q和R226W的存在（在FIX切割位点），导致FIX被因子XIa缺陷性蛋白酶激活（Liddell MB等，1989；Monroe DM等，1989；Suehiro K等，1989；Diuguid DL等，1989；Bertina RM等，1990）。此外，FIX前肽序列中自然发生的点突变如N43Q、N43L或N46S也在此标注。这些FIX变体被分泌到循环中，仍带有未加工的18个氨基酸前肽（Bentley AK等，1986；Galeffi P & Brownlee GG，1987）。发现未加工的FIX变体通过破坏FIX的钙诱导构象来影响蛋白功能（Wojcik EG等，1997），并显示被FXIa激活延迟（Liddell MB等，1989；Ware J等，1989；de la Salle C等，1993；Wojcik EG等，1997；Bristol JA等，1993）。
英文描述
Defective F9 activation Deficiency or dysfunction of FIX leads to hemophilia B (HB), an X-linked, recessive, bleeding disorder. On a molecular basis, HB is due to a heterogeneous spectrum of mutations spread throughout the F9 gene (Rallapalli PM et al. 2013).The Reactome event describes the defective proteolytic activation of FIX by factor XIa due to the presence of HB-associated point mutations R191C, R191H, R226Q and R226W in the cleavage sites of FIX (Liddell MB et al. 1989; Monroe DM et al. 1989; Suehiro K et al. 1989; Diuguid DL et al. 1989; Bertina RM et al.1990). In addition, naturally occurring point mutations in the FIX propeptide sequence such as N43Q, N43L or N46S are also annotated here. These FIX variants are secreted into the circulation with a mutant 18-amino acid propeptide still attached (Bentley AK et al. 1986; Galeffi P & Brownlee GG 1987). The unprocessed FIX variants were found to affect the function of the protein by destabilizing the calcium-induced conformation of FIX (Wojcik EG et al. 1997) and showed delayed activation by FXIa (Liddell MB et al. 1989; Ware J et al. 1989; de la Salle C et al. 1993; Wojcik EG et al. 1997; Bristol JA et al. 1993).
所含基因
5 个基因