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

Molecular cloning of a fourth member of the potassium-dependent sodium-calcium exchanger gene family, NCKX4
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DOI:
10.1074/jbc.m210011200
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发表时间:
2002-12-13
影响因子:
4.8
通讯作者:
Lytton, J
Lytton, J
中科院分区:
生物学2区
文献类型:
--
作者:
Li, XF;Kraev, AS;Lytton, J

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我们在此报告了钾依赖性钠钙交换基因家族第四个成员 NCKX4(基因 SLC24A4)的鉴定和特征,该基因定位于染色体区域 14q32。人 NCKX4 编码 605 个氨基酸的蛋白质,与先前描述的家族成员、视杆细胞 NCKX1(基因 SLC24A1)、视锥细胞/神经元 NCKX2(基因 SLC24A2)和普遍存在的 NCKX3(基因 SLC24A3)在 α 重复序列周围的疏水区域显示出高度的序列同一性。 形成用于运输的离子结合袋。 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,表明这两个基因是由最近的复制事件产生的。 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。当使用 fura-2 荧光数字成像在转染的 HEK293 细胞中进行测定时,NCKX4 蛋白表现出钾依赖性钠钙交换活性。从当前版本的人类基因组序列可以确定,NCKX4的发现完善了哺乳动物钾依赖性钠钙交换基因家族。
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 a-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.