Analysis of the structure and expression pattern of MRP7 (ABCC10), a new member of the MRP subfamily
Analysis of the structure and expression pattern of MRP7 (ABCC10), a new member of the MRP subfamily
复制标题
DOI：
10.1016/s0304-3835(00)00646-7
复制
发表时间：
2001-01-26
期刊：
影响因子：
9.7
通讯作者：
Kruh, GD
中科院分区：
文献类型：
--
作者：
Hopper, E;Belinsky, MG;Kruh, GD
ABC转运蛋白的MRP亚家族目前由至少六个成员组成，其中几个已被证明可以转运两亲性阴离子并赋予体外对化疗药物的耐药性。在搜索数据库时，我们发现了 cDNA 测序项目的产物，该产物与 MRP 亚家族转运蛋白具有显着相似性。在本报告中，分析了该 cDNA（称为 MRP7）的预测编码序列、蛋白质产物和表达模式。 MRP7 cDNA 序列编码一个 1492 个氨基酸的 ABC 转运蛋白，其结构与 MRP1、MRP2、MRP3 和 MRP6 相似，其跨膜螺旋排列在三个跨膜结构域中。然而，与后者的转运蛋白相反，MRP7 的 N 末端没有发现保守的 N 连接糖基化位点。 MRP7氨基酸序列的比较表明，虽然它与其他MRP亚家族成员关系最密切，但其相关程度是所有已知的MRP相关转运蛋白中最低的。通过在用 MRP7 cDNA 编程的网织红细胞裂解物中合成类似于 158 kDa 的蛋白质，证实了预测的 MRP7 编码序列的完整性。虽然通过 RT/PCR 在多种组织中检测到 MRP7 转录物，但通过 RNA 印迹分析不容易检测到它，这表明它在这些组织中以低水平表达。荧光原位杂交表明，MRP7 定位于染色体 6p12-21，靠近与谷胱甘肽缀合和合成相关的多个基因。基于这些发现和进化聚类分析，我们得出结论，MRP7 是两亲性阴离子转运蛋白 MRP 亚家族的成员。 (C) 2001 Elsevier Science Ireland Ltd. 保留所有权利。
The MRP subfamily of ABC transporters currently consists of at least six members, several of which have been demonstrated to transport amphipathic anions and to confer in vitro resistance to chemotherapeutic agents. In searching the data bases we identified the product of a cDNA sequencing project that bears significant similarity to MRP subfamily transporters. In this report the predicted coding sequence, protein product and expression pattern of this cDNA, termed MRP7, are analyzed. The MRP7 cDNA sequence encodes a 1492 amino acid ABC transporter whose structural architecture resembles that of MRP1, MRP2, MRP3, and MRP6, in that its transmembrane helices are arranged in three membrane spanning domains. However, in contrast to the latter transporters, a conserved N-linked glycosylation site is not found at the N-terminus of MRP7. Comparisons of the MRP7 amino acid sequence indicated that while it is most closely related to other MRP subfamily members, its degree of relatedness is the lowest of any of the known MRP-related transporters. The integrity of the predicted MRP7 coding sequence was confirmed by the synthesis of a similar to 158 kDa protein in reticulocyte lysates programmed with the MRP7 cDNA. While MRP7 transcript was detected in a variety of tissues by RT/PCR, it was not readily detectable by RNA blot analysis, suggesting that it is expressed at low levels in these tissues. Fluorescence in situ hybridization indicated that MRP7 maps to chromosome 6p12-21, in proximity to several genes associated with glutathione conjugation and synthesis. On the basis of these findings and evolutionary cluster analysis, we conclude that MRP7 is a member of the MRP subfamily of amphipathic anion transporters. (C) 2001 Elsevier Science Ireland Ltd. All rights reserved.