Overview: ABC transporters and human disease
Overview: ABC transporters and human disease
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DOI：
10.1023/a:1012866803188
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发表时间：
2001-12-01
影响因子：
3
通讯作者：
Ambudkar, SV
中科院分区：
文献类型：
--
作者：
Gottesman, MM;Ambudkar, SV
ABC 转运蛋白存在于所有已知的生物体中，文献中描述了大约 1,100 种属于该家族的不同转运蛋白。该家族由 ATP 结合盒 (ABC) 区域内的同源性定义，该区域延伸到所有 ATP 结合蛋白中发现的更典型的 Walker 基序之外。大多数家族成员还含有参与底物识别的跨膜结构域，这些跨膜结构域可以跨过、进入和离开细胞膜，但有些成员利用 ABC 作为调节离子通道的引擎。人类大约有 50 种已知的 ABC 转运蛋白，目前有 13 种遗传病与其中 14 种转运蛋白的缺陷有关。最常见的遗传性疾病包括囊性纤维化、斯塔加特病、年龄相关性黄斑变性、肾上腺脑白质营养不良、丹吉尔病、杜宾-约翰逊综合征和进行性家族性肝内胆汁淤积。该家族至少有 8 个成员参与多种两亲性化合物（包括抗癌药物）的运输，其中一些似乎有助于癌细胞对化疗的抵抗力。
ABC transporters are found in all known organisms, and approximately 1,100 different transporters belonging to this family have been described in the literature. The family is defined by homology within the ATP-binding cassette (ABC) region, which extends outside of the more typical Walker motifs found in all ATP-binding proteins. Most family members also contain transmembrane domains involved in recognition of substrates, which are transported across, into, and out of cell membranes, but some members utilize ABCs as engines to regulate ion channels. There are approximately 50 known ABC transporters in the human, and there are currently 13 genetic diseases associated with defects in 14 of these transporters. The most common genetic disease conditions include cystic fibrosis, Stargardt disease, age-related macular degeneration, adrenoleukodystrophy, Tangier disease, Dubin-Johnson syndrome and progressive familial intrahepatic cholestasis. At least 8 members of this family are involved in the transport of a variety of amphipathic compounds, including anticancer drugs, and some appear to contribute to the resistance of cancer cells to chemotherapy.