Characterization of MOAT-C and MOAT-D, new members of the MRP/cMOAT subfamily of transporter proteins
Characterization of MOAT-C and MOAT-D, new members of the MRP/cMOAT subfamily of transporter proteins
复制标题
DOI：
10.1093/jnci/90.22.1735
复制
发表时间：
1998-11-18
期刊：
影响因子：
--
通讯作者：
Kruh, GD
中科院分区：
文献类型：
--
作者：
Belinsky, MG;Bain, LJ;Kruh, GD
背景：多药耐药相关蛋白（MRP）和管状多特异性有机阴离子转运蛋白（cMOAT）是将有机阴离子输送到细胞膜上的转运蛋白，与细胞毒性药物的耐药性有关。我们之前通过聚合酶链反应方法鉴定了MRP/ cmoat相关转运蛋白MOAT-B。然而，对表达序列标签（EST）数据库的分析表明，可能存在其他MRP/ cmoat相关转运蛋白。为了进一步确定MRP/cMOAT转运蛋白亚家族，我们使用EST探针分离了两个相关转运蛋白MOAT-C和MOAT-D的互补dna，方法：通过RNA印迹分析确定MOAT-C和MOAT-D在人体组织中的表达模式，并通过荧光原位杂交确定基因的染色体定位。结果：预测MOAT-C编码一个1437个氨基酸的蛋白，在真核转运蛋白中，该蛋白与MRP、cMOAT和MOAT-B的亲缘关系最为密切（同源性约36%）。然而，MOAT-C与MRP和cMOAT的相关性低于MRP和cMOAT之间的相关性（约48%的同一性）。与MOAT-B一样，MOAT-C缺乏一个n端跨膜结构域，这表明该蛋白的拓扑结构与MRP和cMOAT相似，MOAT-D预计编码一个1527个氨基酸的蛋白，这是MRP已知的最接近的亲戚（约58%的同源性）。MOAT-D也与cMOAT高度相关（约47%）。n端跨膜结构域的存在表明MOAT-D的拓扑结构与MRP和cMOAT非常相似，MOAT-C转录本在人体组织中广泛表达；然而，MOAT-D转录本的表达受到更多的限制，MOAT-C和MOAT-D基因分别位于染色体3q27和17q21.3。结论：基于氨基酸特性和蛋白质拓扑结构，MRP/cMOAT转运蛋白亚家族可分为两类；第一组由MRP、cMOAT和MOAT-D组成，第二组由MOAT-B和MOAT-C组成。
Background: Multidrug resistance-associated protein (MRP) and canalicular multispecific organic anion transporter (cMOAT) are transporter proteins that pump organic anions across cellular membranes and have been linked to resistance to cytotoxic drugs. We previously identified MOAT-B, an MRP/cMOAT-related transporter, by use of a polymerase chain reaction approach. However, analysis of expressed sequence tag (EST) databases indicated that there might be additional MRP/cMOAT-related transporters. To further define the MRP/cMOAT subfamily of transporters, we used EST probes to isolate complementary DNAs for two related transporter proteins, MOAT-C and MOAT-D, Methods: MOAT-C and MOAT-D expression patterns in human tissues were determined by RNA blot analysis, and chromosomal localization of the genes was determined by fluorescence in situ hybridization. Results: MOAT-C is predicted to encode a 1437-amino-acid protein that, among eukaryotic transporters, is most closely related to MRP, cMOAT, and MOAT-B (about 36% identity). However, MOAT-C is less related to MRP and cMOAT than MRP and cMOAT are to each other (about 48% identity). Like MOAT-B, MOAT-C lacks an N-terminal membrane-spanning domain, indicating that the topology of this protein is similarly distinct from that of MRP and cMOAT, MOAT-D is predicted to encode a 1527-amino-acid protein that is the closest known relative of MRP (about 58% identity). MOAT-D is also highly related to cMOAT (about 47% identity). The presence of an N-terminal membrane-spanning domain indicates that the topology of MOAT-D is quite similar to that of MRP and cMOAT, MOAT-C transcripts are widely expressed in human tissues; however, MOAT-D transcript expression is more restricted, The MOAT-C and MOAT-D genes are located at chromosomes 3q27 and 17q21.3, respectively. Conclusions: On the basis of amino acid identity and protein topology, the MRP/cMOAT transporter subfamily falls into two groups; the first group consists of MRP, cMOAT, and MOAT-D, and the second group consists of MOAT-B and MOAT-C.