Department of Physiology, Johns Hopkins University, School of Medicine, Baltimore, MD, USA.
FEBS J. 2011 Sep;278(18):3215-25. doi: 10.1111/j.1742-4658.2011.08171.x. Epub 2011 Jun 13.
ATP-binding cassette (ABC) transporters form a large family of transmembrane proteins that facilitate the transport of specific substrates across membranes in an ATP-dependent manner. Transported substrates include lipids, lipopolysaccharides, amino acids, peptides, proteins, inorganic ions, sugars and xenobiotics. Despite this broad array of substrates, the physiological substrate of many ABC transporters has remained elusive. ABC transporters are divided into seven subfamilies, A-G, based on sequence similarity and domain organization. Here we review the role of members of the ABCG subfamily in human disease and how the identification of disease genes helped to determine physiological substrates for specific ABC transporters. We focus on the recent discovery of mutations in ABCG2 causing hyperuricemia and gout, which has led to the identification of urate as a physiological substrate for ABCG2.
三磷酸腺苷结合盒（ABC）转运蛋白形成一个庞大的跨膜蛋白家族，以 ATP 依赖的方式促进特定底物跨膜运输。被转运的底物包括脂类、脂多糖、氨基酸、肽、蛋白质、无机离子、糖和外源性物质。尽管有如此广泛的底物，但许多 ABC 转运蛋白的生理底物仍然难以捉摸。根据序列相似性和结构域组织，ABC 转运蛋白分为七个亚家族，A-G。在这里，我们回顾了 ABCG 亚家族成员在人类疾病中的作用，以及疾病基因的鉴定如何有助于确定特定 ABC 转运蛋白的生理底物。我们重点介绍了最近发现 ABCG2 基因突变导致高尿酸血症和痛风的发现，这导致鉴定尿酸为 ABCG2 的生理底物。
