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钾依赖性钠钙交换器基因家族第四个成员NCKX4的分子克隆

Molecular cloning of a fourth member of the potassium-dependent sodium-calcium exchanger gene family, NCKX4.

作者信息

Li Xiao-Fang, Kraev Alexander S, Lytton Jonathan

机构信息

Department of Biochemistry and Molecular Biology, University of Calgary, Alberta T2N 4N1, Canada.

出版信息

J Biol Chem. 2002 Dec 13;277(50):48410-7. doi: 10.1074/jbc.M210011200. Epub 2002 Oct 11.

DOI:10.1074/jbc.M210011200
PMID:12379639
Abstract

We report here the identification and characterization of a fourth member of the potassium-dependent sodium-calcium exchanger gene family, NCKX4 (gene SLC24A4), which mapped to the chromosomal region 14q32. Human NCKX4 encoded a protein of 605 amino acids that displayed a high level of sequence identity to previously described family members, rod NCKX1 (gene SLC24A1), cone/neuronal NCKX2 (gene SLC24A2), and ubiquitous NCKX3 (gene SLC24A3), in the hydrophobic regions surrounding the alpha-repeat sequences thought to form the ion-binding pocket used for transport. The protein product of the NCKX4 gene shared the highest level of amino acid identity, as well as an almost identical arrangement of exon boundaries, with NCKX3, indicating that these two genes have arisen from a recent duplication event. NCKX4 transcripts were abundantly expressed in all brain regions, aorta, lung, and thymus, as well as at a lower level in many other tissues. The NCKX4 protein demonstrated potassium-dependent sodium calcium exchanger activity when assayed in transfected HEK293 cells using digital imaging of fura-2 fluorescence. The discovery of NCKX4, as far as can be ascertained from the current version of the human genome sequence, completes the mammalian potassium-dependent sodium-calcium exchanger gene family.

摘要

我们在此报告钾依赖性钠钙交换蛋白基因家族第四个成员NCKX4(基因SLC24A4)的鉴定与特性,该基因定位于染色体区域14q32。人类NCKX4编码一种由605个氨基酸组成的蛋白质,在被认为形成用于转运的离子结合口袋的α-重复序列周围的疏水区域,它与先前描述的家族成员杆状NCKX1(基因SLC24A1)、视锥/神经元NCKX2(基因SLC24A2)和普遍存在的NCKX3(基因SLC24A3)显示出高度的序列同一性。NCKX4基因的蛋白质产物与NCKX3具有最高水平的氨基酸同一性,以及几乎相同的外显子边界排列,表明这两个基因源于最近的一次复制事件。NCKX4转录本在所有脑区、主动脉、肺和胸腺中大量表达,在许多其他组织中表达水平较低。当在转染的HEK293细胞中使用fura-2荧光数字成像进行检测时,NCKX4蛋白表现出钾依赖性钠钙交换活性。就目前人类基因组序列版本所能确定的情况而言,NCKX4的发现完善了哺乳动物钾依赖性钠钙交换蛋白基因家族。

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