Sodium proton exchangers (NHEs) constitute a large family of polytopic membrane protein transporters found in organisms across all domains of life. They are responsible for the exchange of protons for sodium ions. In archaea, bacteria, yeast and plants they provide increased salt tolerance by removing sodium in exchanger for extracellular protons. In humans they have a host of physiological functions, the most prominent of which is removal of intracellular protons in exchange for extracellular sodium. Human NHE is also involved in heart disease, cell growth and in cell differentiation. NHE's physiological roles and the intriguing pathological consequences of their actions, make them a very important target of structural and functional studies. There are nine isoforms identified to date in humans. This review provides a brief overview of the human NHE's physiological and pathological roles and cellular/tissue distribution, with special attention to the exemplar member NHE1. A summary of our knowledge to date of the structure and function of NHE1 is included focusing on a discussion of the recent discrepancies reported on the topology of NHE1. Finally we discuss a newly discovered relative of the NHE1 isoform, the Na(+)/Li(+) exchanger, focusing on its predicted topology and its potential roles in disease.

中文翻译：

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人Na + / H +交换异构体1的结构和功能

钠质子交换剂（NHE）构成了生命中所有领域的生物中发现的一大类多聚膜蛋白转运蛋白家族。它们负责质子交换钠离子。在古细菌，细菌，酵母和植物中，它们通过去除交换器中细胞外质子的钠来提供更高的耐盐性。在人类中，它们具有许多生理功能，其中最突出的功能是去除细胞内质子以交换细胞外钠。人类NHE也参与心脏病，细胞生长和细胞分化。NHE的生理作用以及其作用引起的有趣的病理后果，使其成为结构和功能研究的重要目标。迄今为止，已在人类中鉴定出九种亚型。这篇综述简要概述了人类NHE的生理和病理作用以及细胞/组织分布，并特别注意了示例成员NHE1。到目前为止，我们对NHE1的结构和功能的知识进行了总结，重点是对有关NHE1拓扑的最新差异的讨论。最后，我们讨论NHE1亚型的新发现亲戚Na（+）/ Li（+）交换子，重点是其预测的拓扑结构及其在疾病中的潜在作用。