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Molecular characterization of human and rat organic anion transporter OATP-D.

机译:人类和大鼠有机阴离子转运蛋白OATP-D的分子表征。

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摘要

We have isolated and characterized a novel human and rat organic anion transporter subtype, OATP-D. The isolated cDNA from human brain encodes a polypeptide of 710 amino acids (Mr 76,534) with 12 predicted transmembrane domains. The rat clone encodes 710 amino acids (Mr 76,821) with 97.6% amino acid sequence homology with human OATP-D. Human and rat OATP-D have moderate amino acid sequence homology with LST-l/rlst-1, the rat oatp family, the prostaglandin transporter, and moatl/MOAT1/KIAA0880/OATP-B. Phylogenetic tree analysis revealed that OATP-D is branched in a different position from all known organic anion transporters. OATP-D transports prostaglandin E1 (Km 48.5 nM), prostaglandin E2 (Km 55.5 nM), and prostaglandin F2,, suggesting that, functionally, OATP-D encodes a protein that has similar characteristics to those of the prostaglandin transporter. Rat OATP-D also transports prostaglandins. The expression pattern of OATP-D mRNA was abundant mainly in the heart, testis, brain, and some cancer cells. Immunohistochemical analysis further revealed that rat OATP-D is widely expressed in the vascular, renal, and reproductive system at the protein level. These results suggest that OATP-D plays an important role in translocating prostaglandins in specialized tissues and cells.
机译:我们已经分离和表征了一种新型的人类和大鼠有机阴离子转运子亚型,OATP-D。从人脑中分离出的cDNA编码一个710个氨基酸的多肽(Mr 76,534),具有12个预测的跨膜结构域。该大鼠克隆编码710个氨基酸(Mr 76,821),与人的OATP-D的同源性为97.6%。人和大鼠OATP-D与LST-1 / rlst-1,大鼠oatp家族,前列腺素转运蛋白和moatl / MOAT1 / KIAA0880 / OATP-B具有中等氨基酸序列同源性。系统发育树分析表明,OATP-D的分支位置与所有已知的有机阴离子转运蛋白不同。 OATP-D转运前列腺素E1(Km 48.5 nM),前列腺素E2(Km 55.5 nM)和前列腺素F2,这表明OATP-D在功能上编码的蛋白质具有与前列腺素转运蛋白相似的特征。大鼠OATP-D也转运前列腺素。 OATP-D mRNA的表达模式主要在心脏,睾丸,脑和某些癌细胞中丰富。免疫组织化学分析进一步显示,大鼠OATP-D在蛋白质水平广泛表达于血管,肾脏和生殖系统。这些结果表明,OATP-D在特定组织和细胞中的前列腺素转运中起着重要作用。

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