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2.A.19 The Ca2+:Cation Antiporter (CaCA) Family

Proteins of the CaCA family are found ubiquitously, having been identified in animals, plants, yeast, archaea and divergent bacteria. They exhibit widely divergent sequences, and several have been shown to have arisen by a tandem intragenic duplication event (Saier et al., 1999). The most conserved portions of this repeat element, α1 and α2, are found in putative TMSs 2-3 and TMSs 7-8 in the model of Iwamoto et al. (1999). These sequences are important for transport function and may form an intramembranous pore/loop-like structure. These carriers function primarily in Ca2+ extrusion (DiPolo and Beauge, 2006). The human Na+:Ca2+ exchangers, when defective, can cause neurodegenerative disorders (Gomez-Villafuertes et al., 2007).  Allosteric activation of NCX involves the binding of cytosolic Ca2+ to regulatory domains CBD1 and CBD2 (Giladi and Khananshvili 2013).

The CaCA superfamily is composed of five families: K+-independent Na+/Ca2+ exchangers (NCXs), cation/Ca2+ exchangers (CCXs), YbrG transporters and cation exchangers (CAXs). Phylogenetic and alignment studies indicate that one of the mammalian NCKXs, NCKX6 (2.A.19.4.4), and its related proteins form a unique group, designated cation/Ca2+ exchangers (CCXs) (Cai and Lytton, 2004). Cytoplasmic Ca2+ regulates dimeric Na+/Ca2+ exchangers (NCX) by binding to two adjacent Ca2+-binding domains (CBD1 and CBD2) located in the large intracellular loop between transmembrane segments 5 and 6, and produces structural rearrangements (John et al., 2011).  All NCX proteins encoded in the genomes of rice and Arabidopsis have been studied with respect to their phylogeny, domain architecture and expression profiles across different tissues, at various developmental stages and under stress conditions (Singh et al. 2015).

Members of the CaCA family vary in size from 302 amino acyl residues (Methanococcus jannaschii) to 1199 residues (Bos taurus). Even within the animal kingdom, they vary in size from 461 to 1199 residues. The bacterial and archaeal proteins are in general smaller than the eukaryotic proteins (Chung et al., 2001). They have been suggested to traverse the membrane 9 (mammals) or 10 (bacteria) times as α-helical spanners, but some plant homologues (Cax1 and Cax2) exhibit 11 putative TMSs. The E. coli ChaB (YrbG) homologue has been found to have 10 TMSs with both the N- and C-termini localized to the periplasm. Each homologous half of the internally duplicated protein has 5 TMSs with opposite orientation in the membrane (Saaf et al., 2001). This orientation seems to be stabilized by the presence of positively charged residues in the cytoplasmic loops.

The mammalian cardiac muscle homologue probably has 9 TMSs. The N-terminus of this protein is believed to be extracellular, while the C-terminus is intracellular (Iwamoto et al., 1999). A large central loop is not required for transport function and plays a role in regulation. In the preferred 9 TMS model for this mammalian protein, the polypeptide chain loops into the membrane after TMS 2 and after TMS 7. The large central loop separates TMS 5 from TMS 6. TMS 2 and the following loop show sequence similarity to TMS 7 and its loop. TMS 7 may be close to TMSs 2 and 3 in the 3-D structure of the protein (Qui et al., 2001).

The Na+:Ca2+ exchanger plays a central role in cardiac contractility by maintaining Ca2+ homeostasis. Two Ca2+-binding domains, CBD1 and CBD2, located in a large intracellular loop, regulate activity of the exchanger. Ca2+ binding to these regulatory domains activates the transport of Ca2+ across the plasma membrane. The structure of CBD1 shows four Ca2+ ions arranged in a tight planar cluster. The structure of CBD2 in the Ca2+-bound (1.7-Å resolution) and -free (1.4-Å resolution) conformations shows (like CBD1) a classical Ig fold but coordinates only two Ca2+ ions in primary and secondary Ca2+ sites. In the absence of Ca2+, Lys585 stabilizes the structure by coordinating two acidic residues (Asp552 and Glu648), one from each of the Ca2+-binding sites, and prevents protein unfolding (Besserer et al., 2007).

All of the characterized animal proteins catalyze Ca2+:Na+ exchange although some also transport K+. The NCX plasma membrane proteins exchange 3 Na+ for 1 Ca2+ (i.e., 2.A.19.3). Mammalian Na2+/Ca2+ exchangers exist as three isoforms NCX1-3 which are about 70% identical to each other. The NCKX exchangers exchange 1 Ca2+ plus 1 K+ for four Na+ (i.e., 2.A.19.4). The myocyte NCX1.1 splice variant catalyzes Ca2+ extrusion during cardiac relaxation and may catalyze Ca2+ influx during contraction. The E. coli ChaA protein catalyzes Ca2+:H+ antiport but may also catalyze Na+:H+ antiport slowly. All remaining well-characterized members of the family catalyze Ca2+:H+ exchange.

The Na+/Ca2+ exchanger, NCX1 (TC #2.A.19.3.1), is a plasma membrane protein that regulates intracellular Ca2+ levels in cardiac myocytes. Transport activity is regulated by Ca2+, and the primary Ca2+ sensor (CBD1) is located in a large cytoplasmic loop connecting two transmembrane helices. The high-affnity binding of Ca2+ to the CBD1 sensory domain results in conformational changes that stimulate the exchanger to extrude Ca2+. A crystal structure of CBD1 at 2.5Å resolution reveals a novel Ca2+ binding site consisting of four Ca2+ ions arranged in a tight planar cluster. This intricate coordination pattern for a Ca2+ binding cluster is indicative of a highly sensitive Ca2+ sensor and may represent a general platform for Ca2+ sensing Nicoll et al., 2006).

The phylogenetic tree for the CaCA family reveals at least six major branches (Saier et al., 1999). Two clusters consist exclusively of animal proteins, a third contains several bacterial and archaeal proteins, a fourth possesses yeast, plant and blue green bacterial homologues, the fifth contains only the ChaA Ca2+:H+ antiporter of E. coli and the sixth contains only one distant S. cerevisiae homologue of unknown function. Several homologues may be present in a single organism. This fact and the shape of the tree suggest either that isoforms of these proteins arose by gene duplication before the three domains of life split off from each other or that horizontal gene transfer has occurred between these domains (Saier et al., 1999).

Homologues from several cyanobacteria have been characterized. They play important roles in salt tolerance (Waditee et al., 2004).

The generalized transport reaction catalyzed by proteins of the CaCA family is:

Ca2+ (in) + [nH+ or nNa+ (out)] ⇌ Ca2+ (out) + [nH+ or nNa+] (in).


References associated with 2.A.19 family:

Altimimi, H.F., E.H. Fung, R.J. Winkfein, and P.P. Schnetkamp. (2010). Residues contributing to the Na+-binding pocket of the SLC24 Na+/Ca2+-K+ Exchanger NCKX2. J. Biol. Chem. 285: 15245-15255. 20231282
Besserer, G.M., D.A. Nicoll, J. Abramson, and K.D. Philipson. (2012). Characterization and purification of a Na+/Ca2+ exchanger from an archaebacterium. J. Biol. Chem. 287: 8652-8659. 22287543
Besserer, G.M., M. Ottolia, D.A. Nicoll, V.Chaptal, D. Cascio, K.D. Philipson, and J. Abramson. (2007). The second Ca2+-binding domain of the Na+–Ca2+ exchanger is essential for regulation: Crystal structures and mutational analysis. Proc. Natl. Acad. Sci. U.S.A. 104(47):18467-18472. 17962412
Bowman, B.J., S. Abreu, E. Margolles-Clark, M. Draskovic, and E.J. Bowman. (2011). Role of four calcium transport proteins, encoded by nca-1, nca-2, nca-3, and cax, in maintaining intracellular calcium levels in Neurospora crassa. Eukaryot. Cell. 10: 654-661. 21335528
Cagnac, O., M. Leterrier, M. Yeager, and E. Blumwald. (2007). Identification and characterization of Vnx1p, a novel type of vacuolar monovalent cation/H+ antiporter of Saccharomyces cerevisiae. J. Biol. Chem. 282: 24284-24293. 17588950
Cai, X. and J. Lytton. (2004). Molecular cloning of a sixth member of the K+-dependent Na+/Ca2+ exchanger gene family, NCKX6. J. Biol. Chem. 279: 5867-5876. 14625281
Cheng N.H., J.K. Pittman, T. Shigaki, J. Lachmansingh, S. LeClere, B. Lahner, D.E. Salt, K.D. Hirschi. (2005). Functional association of Arabidopsis CAX1 and CAX3 is required for normal growth and ion homeostasis. Plant Physiol. 138: 2048-2060. 16055687
Cheng, N.H., J.K. Pittman, T. Shigaki, and K.D. Hirschi. (2002). Characterization of CAX4, an Arabidopsis H+/cation antiporter. Plant Physiol. 128: 1245-1254. 11950973
Chung, Y.-J., C. Krueger, D. Metzgar, and M.H. Saier, Jr. (2001). Size comparisons among integral membrane transport protein homologues in Bacteria, Archaea, and Eucarya. J. Bacteriol. 183: 1012-1021. 11208800
Cunningham, K.W. and G.R. Fink. (1996). Calcineurin inhibits VCX1-dependent H+/Ca2+ exchange and induces Ca2+ ATPases in Saccharomyces cerevisiae. Mol. Cell. Biol. 16: 2226-2237. 8628289
De Marchi, U., J. Santo-Domingo, C. Castelbou, I. Sekler, A. Wiederkehr, and N. Demaurex. (2014). NCLX protein, but not LETM1, mediates mitochondrial Ca2+ extrusion, thereby limiting Ca2+-induced NAD(P)H production and modulating matrix redox state. J. Biol. Chem. 289: 20377-20385. 24898248
DiPolo, R. and L. Beauge. (2006). Sodium/calcium exchanger: influence of metabolic regulation on ion carrier interactions. Physiol. Rev. 86: 155-203. 16371597
Dong, H., P.E. Light, R.J. French, and J. Lytton. (2001). Electrophysiological characterization and ionic stoichiometry of the rat brain K+-dependent NA(+)/Ca2+ exchanger, NCKX2. J. Biol. Chem. 276: 25919-25928. 11342562
Drago, I., P. Pizzo, and T. Pozzan. (2011). After half a century mitochondrial calcium in- and efflux machineries reveal themselves. EMBO. J. 30: 4119-4125. 21934651
Eide, D.J. (1998). The molecular biology of metal ion transport in Saccharomyces cerevisiae. Annu. Rev. Nutr. 18: 441-469. 9706232
Fujisawa M., Wada Y., Tsuchiya T. and Ito M. (2009). Characterization of Bacillus subtilis YfkE (ChaA): a calcium-specific Ca2+/H+ antiporter of the CaCA family. Arch Microbiol. 191(8):649-57. 19543710
Gaash, R., M. Elazar, K. Mizrahi, M. Avramov-Mor, I. Berezin, and O. Shaul. (2013). Phylogeny and a structural model of plant MHX transporters. BMC Plant Biol 13: 75. 23634958
Giladi, M. and D. Khananshvili. (2013). Molecular determinants of allosteric regulation in NCX proteins. Adv Exp Med Biol 961: 35-48. 23224868
Ginger, R.S., S.E. Askew, R.M. Ogborne, S. Wilson, D. Ferdinando, T. Dadd, A.M. Smith, S. Kazi, R.T. Szerencsei, R.J. Winkfein, P.P. Schnetkamp, and M.R. Green. (2008). SLC24A5 encodes a trans-Golgi network protein with potassium-dependent sodium-calcium exchange activity that regulates human epidermal melanogenesis. J. Biol. Chem. 283(9): 5486-5495. 18166528
Gomez-Villafuertes, R., B. Mellström, and J.R. Naranjo. (2007). Searching for a role of NCX/NCKX exchangers in neurodegeneration. Mol Neurobiol 35: 195-202. 17917108
Gotoh, Y., S. Kita, M. Fujii, H. Tagashira, I. Horie, Y. Arai, S. Uchida, and T. Iwamoto. (2015). Genetic knockout and pharmacologic inhibition of NCX2 cause natriuresis and hypercalciuria. Biochem. Biophys. Res. Commun. 456: 670-675. 25498502
Haynes, W.J., C. Kung, Y. Saimi, and R.R. Preston. (2002). An exchanger-like protein underlies the large Mg2+ current in Paramecium. Proc. Natl. Acad. Sci. USA 99: 15717-15722. 12422021
Hirschi, K.D., R.G. Zhen, K.W. Cunningham, P.A. Rea, and G.R. Fink. (1996). CAX1, an H+/Ca2+ antiporter from Arabidopsis. Proc. Natl. Acad. Sci. USA 93: 8782-8786. 8710949
Ivey, D.M., A.A. Guffanti, J. Zemsky, E. Pinner, R. Karpel, E. Padan, S. Schuldiner, and T.A. Krulwich. (1993). Cloning and characterization of a putative Ca2+/H+ antiporter gene from Escherichia coli upon functional complementation of Na+/H+ antiporter-deficient strains by the overexpressed gene. J. Biol. Chem. 268: 11296-11303. 8496184
Iwamoto, T., T.Y. Nakamura, Y. Pan, A. Uehara, I. Imanaga, and M. Shigekawa. (1999). Unique topology of the internal repeats in the cardiac Na2+/Ca2+ exchanger. FEBS Lett. 446: 264-268. 10100855
John, S.A., B. Ribalet, J.N. Weiss, K.D. Philipson, and M. Ottolia. (2011). Ca2+-dependent structural rearrangements within Na+-Ca2+ exchanger dimers. Proc. Natl. Acad. Sci. USA 108: 1699-1704. 21209335
John, S.A., J. Liao, Y. Jiang, and M. Ottolia. (2013). The cardiac Na+-Ca2+ exchanger has two cytoplasmic ion permeation pathways. Proc. Natl. Acad. Sci. USA 110: 7500-7505. 23589872
Kofuji, P., R.W. Hadley, R.S. Kieval, W.J. Lederer, and D.H. Schulze. (1992). Expression of the Na-Ca exchanger in diverse tissues: a study using the cloned human cardiac Na-Ca exchanger. Am. J. Physiol. 263: C1241-1249. 1476165
Komuro, I., K.E. Wenninger, K.D. Philipson, and S. Izumo. (1992). Molecular cloning and characterization of the human cardiac Na+/Ca2+ exchanger cDNA. Proc. Natl. Acad. Sci. USA 89: 4769-4773. 1374913
Kraev, A., B.D. Quednau, S. Leach, X.-F. Li, H. Dong, R. Winkfein, M. Perizzolo, X. Cai, R. Yang, K.D. Philipson, and J. Lytton. (2001). Molecular cloning of a third member of the potassium-dependent sodium-calcium exchanger gene family, NCKX3. J. Biol. Chem. 276: 23161-23172. 11294880
Lamoureux, G., A. Javelle, S. Baday, S. Wang, and S. Bernèche. (2010). Transport mechanisms in the ammonium transporter family. Transfus Clin Biol 17: 168-175. 20674437
Li, X.F., Kiedrowski, L., Tremblay, F., Fernandez, F.R., Perizzolo, M., Winkfein, R.J., Turner, R.W., Bains, J.S., Rancourt, D.E., and Lytton, J. (2006). Importance of K+-dependent Na+/Ca2+-exchanger 2, NCKX2, in motor learning and memory. J. Biol. Chem. 281: 6273-6282. 16407245
Liao, J., H. Li, W. Zeng, D.B. Sauer, R. Belmares, and Y. Jiang. (2012). Structural insight into the ion-exchange mechanism of the sodium/calcium exchanger. Science 335: 686-690. 22323814
Marinelli, F., L. Almagor, R. Hiller, M. Giladi, D. Khananshvili, and J.D. Faraldo-Gómez. (2014). Sodium recognition by the Na+/Ca2+ exchanger in the outward-facing conformation. Proc. Natl. Acad. Sci. USA 111: E5354-5362. 25468964
Mei, H., N.H. Cheng, J. Zhao, S. Park, R.A. Escareno, J.K. Pittman, and K.D. Hirschi. (2009). Root development under metal stress in Arabidopsis thaliana requires the H+/cation antiporter CAX4. New Phytol 183: 95-105. 19368667
Morris, J., H. Tian, S. Park, C.S. Sreevidya, J.M. Ward, and K.D. Hirschi. (2008). AtCCX3 is an Arabidopsis endomembrane H+ -dependent K+ transporter. Plant Physiol. 148: 1474-1486. 18775974
Nicoll, D.A., M. Ottolia, L. Lu, Y. Lu, and K.D. Philipson. (1999). A new topological model of the cardiac sarcolemmal Na+-Ca2+ exchanger. J. Biol. Chem. 274: 910-917. 9873031
Nicoll, D.A., M.R. Sawaya, S. Kwon, D. Cascio, K.D. Philipson, and J. Abramson. (2006). The crystal structure of the primary Ca2+ sensor of the Na+/Ca2+ exchanger reveals a novel Ca2+ binding motif. J. Biol. Chem. 281: 21577-21581. 16774926
Nicoll, D.A., S. Longoni, and E.K. Philipson. (1990). Molecular cloning and functional expression of the cardiac sarcolemmal Na+-Ca2+ exchanger. Science 250: 562-565. 1700476
Nishiyama, K., K. Tanioka, Y.T. Azuma, S. Hayashi, Y. Fujimoto, N. Yoshida, S. Kita, S. Suzuki, H. Nakajima, T. Iwamoto, and T. Takeuchi. (2016). Na+/Ca2+ exchanger contributes to stool transport in mice with experimental diarrhea. J Vet Med Sci. [Epub: Ahead of Print] 27928109
Nishizawa, T., S. Kita, A.D. Maturana, N. Furuya, K. Hirata, G. Kasuya, S. Ogasawara, N. Dohmae, T. Iwamoto, R. Ishitani, and O. Nureki. (2013). Structural basis for the counter-transport mechanism of a H+/Ca2+ exchanger. Science 341: 168-172. 23704374
Ottolia, M. and K.D. Philipson. (2013). NCX1: mechanism of transport. Adv Exp Med Biol 961: 49-54. 23224869
Preston, R.R. and C. Kung. (1994). Isolation and characterization of paramecium mutants defective in their response to magnesium. Genetics 137: 759-769. 8088522
Qiu, Z., D.A. Nicoll, and K.D. Philipson. (2001). Helix packing of functionally important regions of the cardiac Na+-Ca2+ exchanger. J. Biol. Chem. 276: 194-199. 11035002
Radchenko, M.V., K. Tanaka, R. Waditee, S. Oshimi, Y. Matsuzaki, M. Fukuhara, H. Kobayashi, T. Takabe, and T. Nakamura. (2006). Potassium/proton antiport system of Escherichia coli. J. Biol. Chem. 281: 19822-19829. 16687400
Reeves, J.P. (1998). Na2+/Ca2+ exchange and cellular Ca2+ homeostasis. J. Bioenerg. Biomembr. 30: 151-160. 9672237
Ren, X. and K.D. Philipson. (2013). The topology of the cardiac Na⁺/Ca²⁺ exchanger, NCX1. J Mol. Cell Cardiol 57: 68-71. 23376057
Ren, X., D.A. Nicoll, and K.D. Philipson. (2006). Helix packing of the cardiac Na+-Ca2+ exchanger: proximity of transmembrane segments 1, 2, and 6. J. Biol. Chem. 281: 22808-22814. 16785232
Ren, X., D.A. Nicoll, G. Galang, and K.D. Philipson. (2008). Intermolecular cross-linking of Na+-Ca2+ exchanger proteins: evidence for dimer formation. Biochemistry 47: 6081-6087. 18465877
Ren, X., D.A. Nicoll, L. Xu, Z. Qu, and K.D. Philipson. (2010). Transmembrane segment packing of the Na+/Ca2+ exchanger investigated with chemical cross-linkers. Biochemistry 49: 8585-8591. 20735122
Ridilla M., Narayanan A., Bolin JT. and Yernool DA. (2012). Identification of the dimer interface of a bacterial Ca(2+)/H(+) antiporter. Biochemistry. 51(48):9603-11. 23134204
Sääf, A., L. Baars, and G. von Heijne. (2001). The internal repeats in the Na+/Ca2+ exchanger-related Escherichia coli protein YrbG have opposite membrane topologies. J. Biol. Chem. 276: 18905-18907. 11259419
Saier, M.H., Jr., B.H. Eng, S. Fard, J. Garg, D.A. Haggerty, W.J. Hutchinson, D.L. Jack, E.C. Lai, H.J. Liu, D.P. Nusinew, A.M. Omar, S.S. Pao, I.T. Paulsen, J.A. Quan, M. Sliwinski, T.-T. Tseng, S. Wachi, and G.B. Young. (1999). Phylogenetic characterization of novel transport protein families revealed by genome analyses. Biochim. Biophys. Acta 1422: 1-56. 10082980
Schwarz E.M., Benzer S. (1997). Calx, a Na-Ca exchanger gene of Drosophila melanogaster. Proc. Natl. Acad. Sci U.S.A. 94: 10249-10254. 9294196
Secondo, A., G. Pignataro, P. Ambrosino, A. Pannaccione, P. Molinaro, F. Boscia, M. Cantile, O. Cuomo, A. Esposito, M.J. Sisalli, A. Scorziello, N. Guida, S. Anzilotti, F. Fiorino, B. Severino, V. Santagada, G. Caliendo, G. Di Renzo, and L. Annunziato. (2015). Pharmacological characterization of the newly synthesized 5-amino-N-butyl-2-(4-ethoxyphenoxy)-benzamide hydrochloride (BED) as a potent NCX3 inhibitor that worsens anoxic injury in cortical neurons, organotypic hippocampal cultures, and ischemic brain. ACS Chem Neurosci 6: 1361-1370. 25942323
Segarra, V.A. and L. Thomas. (2008). Topology mapping of the vacuolar Vcx1p Ca2+/H+ exchanger from Saccharomyces cerevisiae. Biochem. J. 414: 133-141. 18447831
Sharma, V., S. Roy, I. Sekler, and D.M. O''Halloran. (2017). The NCLX-type Na+/Ca2+ exchanger NCX-9 is required for patterning of neural circuits in Caenorhabditis elegans. J. Biol. Chem. [Epub: Ahead of Print] 28196860
Shaul O., D.W. Hilgemann, J. de-Almeida-Engler, M. Van Montagu, D. Inze, G. Galili. (1999). Cloning and characterization of a novel Mg(2+)/H(+) exchanger. EMBO. J. 18: 3973-3980. 10406802
Shenoda, B. (2015). The role of Na+/Ca2+ exchanger subtypes in neuronal ischemic injury. Transl Stroke Res 6: 181-190. 25860439
Shigaki, T., Barkla, B.J., Miranda-Vergara, M.C., Zhao, J., Pantoja, O., and Hirschi, K.D. (2005). Identification of a crucial histidine involved in metal transport activity in the Arabidopsis cation/H+ exchanger CAX1. J. Biol. Chem. 280: 30136-30142. 15994298
Shigaki, T., J.K. Pittman, and K.D. Hirschi. (2003). Manganese specificity determinants in the Arabidopsis metal/H+ antiporter CAX2. J. Biol. Chem. 278: 6610-6617. 12496310
Shigaki, T., N. Cheng, J.K. Pittman, and K. Hirschi. (2001). Structural determinants of Ca2+ transport in the Arabidopsis H+/Ca2+ antiporter CAX1. J. Biol. Chem. 276: 43152-43159. 11562366
Singh, A.K., R. Kumar, A.K. Tripathi, B.K. Gupta, A. Pareek, and S.L. Singla-Pareek. (2015). Genome-wide investigation and expression analysis of Sodium/Calcium exchanger gene family in rice and Arabidopsis. Rice (N Y) 8: 54. 26134707
Su, Y.-H. and V.D. Vacquier. (2002). A flagellar K+-dependent Na+/Ca2+ exchanger keeps Ca2+ low in sea urchin spermatozoa. Proc. Natl. Acad. Sci. USA 99: 6743-6748. 12011436
Thakur, A. and A.K. Bachhawat. (2010). The role of transmembrane domain 9 in substrate recognition by the fungal high-affinity glutathione transporters. Biochem. J. 429: 593-602. 20477749
Van Eylen, F., A. Bollen, and A. Herchuelz. (2001). NCX1 Na/Ca exchanger splice variants in pancreatic islet cells. J Endocrinol 168: 517-526. 11241183
Visser, F., V. Valsecchi, L. Annunziato, and J. Lytton. (2007). 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. 282: 4453-4462.
Waditee, R., G.S. Hossain, Y. Tanaka, T. Nakamura, M. Shikata, J. Takano, T. Takabe, and T. Takabe. (2004). Isolation and functional characterization of Ca2+/H+ antiporters from cyanobacteria. J. Biol. Chem. 279: 4330-4338. 14559898
Waight, A.B., B.P. Pedersen, A. Schlessinger, M. Bonomi, B.H. Chau, Z. Roe-Zurz, A.J. Risenmay, A. Sali, and R.M. Stroud. (2013). Structural basis for alternating access of a eukaryotic calcium/proton exchanger. Nature 499: 107-110. 23685453
Wang S., Choi M., Richardson AS., Reid BM., Seymen F., Yildirim M., Tuna E., Gencay K., Simmer JP. and Hu JC. (2014). STIM1 and SLC24A4 Are Critical for Enamel Maturation. J Dent Res. 93(7 Suppl):94S-100S. 24621671
Wei, Y., J. Liu, Y. Ma, and T.A. Krulwich. (2007). Three putative cation/proton antiporters from the soda lake alkaliphile Alkalimonas amylolytica N10 complement an alkali-sensitive Escherichia coli mutant. Microbiology. 153: 2168-2179. 17600061
Wu, M., S. Tong, J. Gonzalez, V. Jayaraman, J.L. Spudich, and L. Zheng. (2011). Structural basis of the Ca2+ inhibitory mechanism of Drosophila Na+/Ca2+ exchanger CALX and its modification by alternative splicing. Structure 19: 1509-1517. 22000518
Yamada N., Theerawitaya C., Cha-um S., Kirdmanee C. and Takabe T. (2014). Expression and functional analysis of putative vacuolar Ca2+-transporters (CAXs and ACAs) in roots of salt tolerant and sensitive rice cultivars. Protoplasma. 251(5):1067-75. 24482191
Zhang, X., M. Zhang, T. Takano, and S. Liu. (2011). Characterization of an AtCCX5 gene from Arabidopsis thaliana that involves in high-affinity K+ uptake and Na+ transport in yeast. Biochem. Biophys. Res. Commun. 414: 96-100. 21945443
Zhao, J., B.J. Barkla, J. Marshall, J.K. Pittman, and K.D. Hirschi. (2008). The Arabidopsis cax3 mutants display altered salt tolerance, pH sensitivity and reduced plasma membrane H+-ATPase activity. Planta. 227: 659-669. 17968588