Ogawa Mitsutaka, Sawaguchi Shogo, Furukawa Koichi, Okajima Tetsuya
Department of Biochemistry II, Nagoya University Graduate School of Medicine, 65 Tsurumai, Showa-ku, Nagoya 466-0065, Japan; Department of Bioscience, Nagahama Institute of Bio-Science and Technology, 1266 Tamura, Nagahama, Shiga 526-0829, Japan.
Department of Biochemistry II, Nagoya University Graduate School of Medicine, 65 Tsurumai, Showa-ku, Nagoya 466-0065, Japan.
Biochim Biophys Acta. 2015 Jun;1850(6):1319-24. doi: 10.1016/j.bbagen.2015.03.003. Epub 2015 Mar 17.
O-linked β-N-acetylglucosamine (O-GlcNAc) modification of epidermal growth factor (EGF) domains catalyzed by EGF domain O-GlcNAc transferase (EOGT) is the first example of GlcNAc modification in the lumen of the endoplasmic reticulum (ER).
This review summarizes current knowledge on the EOGT-catalyzed O-GlcNAc modification of EGF domains obtained through biochemical characterization, genetic analysis in Drosophila, and identification of human EOGT mutation. Additionally, this review discusses GTDC2-another ER protein homologous to EOGT that catalyzes the GlcNAc modification of O-mannosylated α-dystroglycan-and other components of the biosynthetic pathway involved in GlcNAc modification in the ER lumen.
GlcNAc modification in the ER lumen has been identified as a novel type of protein modification that regulates specific protein function. Moreover, abnormal GlcNAc modification in the ER lumen is responsible for Adams-Oliver syndrome and Walker-Warburg syndrome.
Elucidation of the biological function of GlcNAc modification in the ER lumen will provide new insights into the unique roles of O-glycans, whose importance has been demonstrated in multifunctional glycoproteins such as Notch receptors and α-dystroglyan.
由表皮生长因子结构域O-连接的N-乙酰葡糖胺（O-GlcNAc）转移酶（EOGT）催化的表皮生长因子（EGF）结构域的O-GlcNAc修饰是内质网（ER）腔中GlcNAc修饰的首个实例。
本综述总结了通过生化特性分析、果蝇的遗传分析以及人类EOGT突变鉴定所获得的关于EOGT催化的EGF结构域O-GlcNAc修饰的现有知识。此外，本综述还讨论了GTDC2——另一种与EOGT同源的内质网蛋白，它催化O-甘露糖基化的α- dystroglycan的GlcNAc修饰以及内质网腔中参与GlcNAc修饰的生物合成途径的其他成分。
内质网腔中的GlcNAc修饰已被确定为一种调节特定蛋白质功能的新型蛋白质修饰。此外，内质网腔中异常的GlcNAc修饰是亚当斯-奥利弗综合征和沃克-沃尔堡综合征的病因。
阐明内质网腔中GlcNAc修饰的生物学功能将为O-聚糖的独特作用提供新的见解，其重要性已在Notch受体和α-dystroglyan等多功能糖蛋白中得到证明。
