Functional and Structural Analysis on Familial Moyamoya Disease Associated Novel Huge Ubiquitin Ligase/ATPase

我们鉴定了Mysterin/RNF213是家族性烟雾病的易感基因，并成功地克隆了它的cDNA。进一步，我们揭示了它在细胞内的分布，泛素连接酶和ATPase的活性，以及它在正常发育过程中参与适当的血管生成。利用纯化的奥秘蛋白，我们揭示了其结构性质。此外，我们通过细胞内免疫共沉淀分析鉴定了去泛素化酶是一种神秘蛋白结合蛋白，并揭示了该酶在功能上与神秘蛋白相关。

We identified mysterin/RNF213 as a familial moyamoya disease susceptible gene, and succeeded to clone its cDNA. Further, we revealed its intracellular distribution, ubiquitin ligase and ATPase activities, and its participation in proper angiogenesis during normal development. Using purified mysterin protein, we revealed its structural properties. Moreover, we identified de-ubiquitinating enzyme as a mysterin binding protein through intracellular coimmunoprecipitation analysis, and revealed that the enzyme functionally associates with mysterin.