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Originally published In Press as doi:10.1074/jbc.M210011200 on October 11, 2002

J. Biol. Chem., Vol. 277, Issue 50, 48410-48417, December 13, 2002
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Molecular Cloning of a Fourth Member of the Potassium-dependent Sodium-Calcium Exchanger Gene Family, NCKX4*

Xiao-Fang LiDagger , Alexander S. Kraev§, and Jonathan LyttonDagger

From the Dagger  Department of Biochemistry and Molecular Biology, University of Calgary, Calgary, Alberta T2N 4N1, Canada and the § Samuel Lunenfeld Research Institute, Mt. Sinai Hospital, Toronto, Ontario M5G 1X5, Canada

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.

* This work was supported by grants from the Canadian Institutes of Health Research and the Alberta Heritage Foundation for Medical Research (to J. L.).The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

The nucleotide sequence(s) reported in this paper has been submitted to the GenBankTM/EBI Data Bank with accession number(s) AF520704, AF520705, AF520706, and AY156046.

Senior Scholar of the Alberta Heritage Foundation for Medical Research and an Investigator of the Canadian Institutes of Health Research. To whom correspondence should be addressed: University of Calgary Health Science Center, 3330 Hospital Dr., NW, Calgary, AB T2N 4N1, Canada. Tel.: 403-220-2893; Fax: 403-283-4841; E-mail: jlytton@ucalgary.ca.

Copyright © 2002 by The American Society for Biochemistry and Molecular Biology, Inc.
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