Submitted to: Journal of Molecular Evolution
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 7/21/2006
Publication Date: 12/1/2006
Citation: Shigaki, T., Rees, I., Nakhleh, L., Hirschi, K.D. 2006. Identification of three distinct phylogenetic groups of CAX Cation/Proton Antiporters. Journal of Molecular Evolution. 63(6):815-825. Interpretive Summary: In order to understand the biological function of various proteins it is first important to classify the proteins into "types" or "families". These computer approximations look at the protein sequence to help guide future experimental tests that directly relate to biological function. Here we have classified transporters into different families to help make first approximations regarding function. These computer-based approximations will guide future studies that attempt to engineer these transporters to make healthier plants for human consumption.
Technical Abstract: Ca[2+]/cation antiporter (CaCA) proteins are integral membrane proteins that transport Ca[2+] or other cations using the H[+] or Na[+] gradient generated by primary transporters. The CAX (for CAtion eXchanger) family is one of the five families that make up the CaCA superfamily. CAX genes have been found in bacteria, "Dictyostelium", fungi, plants, and lower vertebrates, but only a small number of CAXs have been functionally characterized. In this study, we explored the diversity of CAXs and their phylogenetic relationships. The results demonstrate that there are three major types of CAXs: type I (CAXs similar to "Arabidopsis thaliana" CAX1, found in plants, fungi, and bacteria), type II (CAXs with a long N-terminus hydrophilic region, found in fungi, "Dictyostelium", and lower vertebrates), and type III (CAXs similar to "Escherichia coli" ChaA, found in bacteria). Some CAXs were found to have secondary structures that are different from the canonical six transmembrane (TM) domains–acidic motif-five TM domain structure. Our phylogenetic tree indicated no evidence to support the cyanobacterial origin of plant CAXs or the classification of "Arabidopsis" exchangers CAX7 to CAX11. For the first time, these results clearly define the CAX exchanger family and its subtypes in phylogenetic terms. The surprising diversity of CAXs demonstrates their potential range of biochemical properties and physiologic relevance.