MBE Advance Access originally published online on May 26, 2004
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Mol. Biol. Evol. 21(9):1692-1703. 2004
DOI: 10.1093/molbev/msh177
© 2004 by the Society for Molecular Biology and Evolution. ISSN: 0737-4038
The Cation/Ca2+ Exchanger Superfamily: Phylogenetic Analysis and Structural Implications
The Cardiovascular Research Group, Departments of Biochemistry and Molecular Biology and Physiology and Biophysics, University of Calgary, Calgary, Alberta, Canada
E-mail: x.cai{at}cellbio.duke.edu.
Cation/Ca2+ exchangers are an essential component of Ca2+ signaling pathways and function to transport cytosolic Ca2+ across membranes against its electrochemical gradient by utilizing the downhill gradients of other cation species such as H+, Na+, or K+. The cation/Ca2+ exchanger superfamily is composed of H+/Ca2+ exchangers and Na+/Ca2+ exchangers, which have been investigated extensively in both plant cells and animal cells. Recently, information from completely sequenced genomes of bacteria, archaea, and eukaryotes has revealed the presence of genes that encode homologues of cation/Ca2+ exchangers in many organisms in which the role of these exchangers has not been clearly demonstrated. In this study, we report a comprehensive sequence alignment and the first phylogenetic analysis of the cation/Ca2+ exchanger superfamily of 147 sequences. The results present a framework for structure-function relationships of cation/Ca2+ exchangers, suggesting unique signature motifs of conserved residues that may underlie divergent functional properties. Construction of a phylogenetic tree with inclusion of cation/Ca2+ exchangers with known functional properties defines five protein families and the evolutionary relationships between the members. Based on this analysis, the cation/Ca2+ exchanger superfamily is classified into the YRBG, CAX, NCX, and NCKX families and a newly recognized family, designated CCX. These findings will provide guides for future studies concerning structures, functions, and evolutionary origins of the cation/Ca2+ exchangers.
Key Words: membrane protein • ionic transporter • phylogeny • Na+/Ca2+ exchangers • H+/Ca2+ exchangers • gene duplication
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  J. Zhao, T. Shigaki, H. Mei, Y.-q. Guo, N.-H. Cheng, and K. D. Hirschi Interaction between Arabidopsis Ca2+/H+ Exchangers CAX1 and CAX3 J. Biol. Chem., February 13, 2009; 284(7): 4605 - 4615. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. K. Pittman, C. Edmond, P. A. Sunderland, and C. M. Bray A Cation-regulated and Proton Gradient-dependent Cation Transporter from Chlamydomonas reinhardtii Has a Role in Calcium and Sodium Homeostasis J. Biol. Chem., January 2, 2009; 284(1): 525 - 533. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. On, C. R. Marshall, S. F. Perry, H. D. Le, V. Yurkov, A. Omelchenko, M. Hnatowich, L. V. Hryshko, and G. F. Tibbits Characterization of zebrafish (Danio rerio) NCX4: a novel NCX with distinct electrophysiological properties Am J Physiol Cell Physiol, January 1, 2009; 296(1): C173 - C181. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Morris, H. Tian, S. Park, C. S. Sreevidya, J. M. Ward, and K. D. Hirschi AtCCX3 Is an Arabidopsis Endomembrane H+-Dependent K+ Transporter Plant Physiology, November 1, 2008; 148(3): 1474 - 1486. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 X. Cai Unicellular Ca2+ Signaling 'Toolkit' at the Origin of Metazoa Mol. Biol. Evol., July 1, 2008; 25(7): 1357 - 1361. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. S. Ginger, S. E. Askew, R. M. Ogborne, S. Wilson, D. Ferdinando, T. Dadd, A. M. Smith, S. Kazi, R. T. Szerencsei, R. J. Winkfein, et al. SLC24A5 Encodes a trans-Golgi Network Protein with Potassium-dependent Sodium-Calcium Exchange Activity That Regulates Human Epidermal Melanogenesis J. Biol. Chem., February 29, 2008; 283(9): 5486 - 5495. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 O. Cuomo, R. Gala, G. Pignataro, F. Boscia, A. Secondo, A. Scorziello, A. Pannaccione, D. Viggiano, A. Adornetto, P. Molinaro, et al. A Critical Role for the Potassium-Dependent Sodium-Calcium Exchanger NCKX2 in Protection against Focal Ischemic Brain Damage J. Neurosci., February 27, 2008; 28(9): 2053 - 2063. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. A. Berkowitz, R. Roberts, A. Stemmler, H. Luan, and M. Gradianu Impaired Apparent Ion Demand in Experimental Diabetic Retinopathy: Correction by Lipoic Acid Invest. Ophthalmol. Vis. Sci., October 1, 2007; 48(10): 4753 - 4758. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
O. Cagnac, M. Leterrier, M. Yeager, and E. Blumwald Identification and Characterization of Vnx1p, a Novel Type of Vacuolar Monovalent Cation/H+ Antiporter of Saccharomyces cerevisiae J. Biol. Chem., August 17, 2007; 282(33): 24284 - 24293. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Wei, J. Liu, Y. Ma, and T. A. Krulwich Three putative cation/proton antiporters from the soda lake alkaliphile Alkalimonas amylolytica N10 complement an alkali-sensitive Escherichia coli mutant Microbiology, July 1, 2007; 153(7): 2168 - 2179. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F. Visser and J. Lytton K+-Dependent Na+/Ca2+ Exchangers: Key Contributors to Ca2+ Signaling Physiology, June 1, 2007; 22(3): 185 - 192. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. Visser, V. Valsecchi, L. Annunziato, and J. Lytton Analysis of Ion Interactions with the K+ -dependent Na+/Ca+ Exchangers NCKX2, NCKX3, and NCKX4: IDENTIFICATION OF THR-551 AS A KEY RESIDUE IN DEFINING THE APPARENT K+ AFFINITY OF NCKX2 J. Biol. Chem., February 16, 2007; 282(7): 4453 - 4462. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. Martinoia, M. Maeshima, and H. E. Neuhaus Vacuolar transporters and their essential role in plant metabolism J. Exp. Bot., January 1, 2007; 58(1): 83 - 102. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
X.-F. Li, L. Kiedrowski, F. Tremblay, F. R. Fernandez, M. Perizzolo, R. J. Winkfein, R. W. Turner, J. S. Bains, D. E. Rancourt, and J. Lytton Importance of K+-dependent Na+/Ca2+-exchanger 2, NCKX2, in Motor Learning and Memory J. Biol. Chem., March 10, 2006; 281(10): 6273 - 6282. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
X. Cai and Y. Zhang Molecular Evolution of the Ankyrin Gene Family Mol. Biol. Evol., March 1, 2006; 23(3): 550 - 558. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. L. Lamason, M.-A. P.K. Mohideen, J. R. Mest, A. C. Wong, H. L. Norton, M. C. Aros, M. J. Jurynec, X. Mao, V. R. Humphreville, J. E. Humbert, et al. SLC24A5, a Putative Cation Exchanger, Affects Pigmentation in Zebrafish and Humans Science, December 16, 2005; 310(5755): 1782 - 1786. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Shigaki, B. J. Barkla, M. C. Miranda-Vergara, J. Zhao, O. Pantoja, and K. D. Hirschi Identification of a Crucial Histidine Involved in Metal Transport Activity in the Arabidopsis Cation/H+ Exchanger CAX1 J. Biol. Chem., August 26, 2005; 280(34): 30136 - 30142. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. R. Marshall, T.-C. Pan, H. D. Le, A. Omelchenko, P. P. Hwang, L. V. Hryshko, and G. F. Tibbits cDNA Cloning and Expression of the Cardiac Na+/Ca2+ Exchanger from Mozambique Tilapia (Oreochromis mossambicus) Reveal a Teleost Membrane Transporter with Mammalian Temperature Dependence J. Biol. Chem., August 12, 2005; 280(32): 28903 - 28911. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. R. Marshall, J. A. Fox, S. L. Butland, B. F. F. Ouellette, F. S. L. Brinkman, and G. F. Tibbits Phylogeny of Na+/Ca2+ exchanger (NCX) genes from genomic data identifies new gene duplications and a new family member in fish species Physiol Genomics, April 14, 2005; 21(2): 161 - 173. [Abstract] [Full Text] [PDF]
|
|