Molecular cloning and characterization of NKT, a gene product related to the organic cation transporter family that is almost exclusively expressed in the kidney
Molecular cloning and characterization of NKT, a gene product related to the organic cation transporter family that is almost exclusively expressed in the kidney
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DOI：
10.1074/jbc.272.10.6471
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发表时间：
1997-03-07
影响因子：
4.8
通讯作者：
Nigam, SK
中科院分区：
文献类型：
--
作者：
LopezNieto, CE;You, GF;Nigam, SK
我们已经鉴定了一种基因产物（NKT），其编码一种似乎与有机离子转运蛋白家族相关的明显新颖的转录物，并且几乎只在肾脏中表达，对推导的546个氨基酸的蛋白质序列的分析表明，NKT是一种独特的基因产物，它具有类似的跨膜结构域亲水性和转运蛋白-NKT与多种细菌和哺乳动物营养转运蛋白具有特异性氨基酸基序，然而，NKT与最近克隆的两种有机离子转运蛋白的总体同源性不高，（NLT和OCT-1）显著更大;这三种基因产物一起可以代表转运蛋白的一个新亚组，NKT的特征进一步关于其组织分布和其在肾脏发育过程中的表达。在肾脏中发现了2.5-羟色胺酶转录物，在脑中的水平低得多，但在许多其他组织中没有。对胚胎肾脏的研究表明，NKT转录物在发育中受到调节，在小鼠妊娠第18天开始显著表达，并在出生前上升，这与分化的肾功能中的作用一致。原位杂交检测到小鼠肾近端小管中的特异性信号。通过连锁不平衡将NKT定位于小鼠19号染色体，这是几种小鼠突变定位的同一位点，包括骨软骨营养不良（ocd）。虽然在非洲爪蟾卵母细胞表达系统中的初始实验未能证明OCT-1的已知底物的转运，但OCT-1和其他转运蛋白的同源性，沿着近端小管定位，提高了该基因可能在有机溶质转运或肾脏药物消除中发挥作用的可能性。
We have identified a gene product (NKT) encoding an apparently novel transcript that appears to be related to the organic ion transporter family and is expressed al most exclusively in the kidney, Analysis of the deduced 546-amino acid protein sequence indicates that NKT is a unique gene product which shares a similar transmembrane domain hydropathy profile as well as transporter-specific amino acid motifs with a variety of bacterial and mammalian nutrient transporters, Nevertheless, the overall homology of NKT to two recently cloned organic ion transport proteins (NLT and OCT-1) is significantly greater; together these three gene products may represent a new subgroup of transporters, The NKT was characterized further with respect to its tissue distribution and its expression during kidney development. A 2.5-kilobase transcript was found in kidney and at much lower levels in brain, but not in a number of other tissues, Studies on the embryonic kidney indicate that the NKT transcript is developmentally regulated with significant expression beginning at mouse gestational day 18 and rising just before birth, consistent with a role in differentiated kidney function, Moreover, in situ hybridization detected specific signals in mouse renal proximal tubules. NKT was mapped by linkage disequilibrium to mouse chromosome 19, the same site to which several mouse mutations localize, including that for osteochondrodystrophy (ocd). Although initial experiments in a Xenopus oocyte expression system failed to demonstrate transport of known substrates for OCT-1, the homology to OCT-1 and other transporters, along with the proximal tubule localization, raise the possibility that this gene may play a role in organic solute transport or drug elimination by the kidney.