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9.A.43 The Cadmium Tolerance Efflux Pump (CTEP) Family

Cadmium (Cd) causes the generation of reactive oxygen species (ROS), which in turn causes cell damage. Kim et al (2008) isolated a novel gene from a wheat root cDNA library, which conferred Cd2+-specific tolerance when expressed in Saccharomyces cerevisiae. The gene, called TaTM20, for Triticum aestivum transmembrane 20, encodes a hydrophobic polypeptide of 889 amino acids, containing 20 transmembrane domains arranged as a 5-fold internal repeating unit of 4 transmembrane domains each. Expression of TaTM20 in yeast cells stimulated Cd2+ efflux resulting in a decrease in the content of yeast intracellular Cd2+. TaTM20-induced Cd2+ tolerance was maintained in yeast even under conditions of reduced glutathione (GSH). Thus, TaTM20 enhances Cd2+ tolerance in yeast through the stimulation of Cd2+ efflux from the cell, partially independent of GSH. Treatment of wheat seedlings with Cd2+ induced their expression of TaTM20, decreasing subsequent root Cd2+ accumulation and suggesting a possible role for TaTM20 in Cd2+ tolerance in wheat (Kim et al. 2008). 

The proteins of this family seem to be exclusively from plants, but many of them do not have the 4 TMS repeats.  They instead each have a single 4 TMS unit, usually at their C-termini.  It is possible that these proteins are related to the bacterial protein in TC family 9.B.257, but this has not been examined carefully. 

The multi-pass transmembrane protein ACCELERATED CELL DEATH 6 (ACD6) is an immune regulator in Arabidopsis thaliana.  Chen et al. 2023 identified two loci, MODULATOR OF HYPERACTIVE ACD6 1 (MHA1) and its paralog MHA1-LIKE (MHA1L), that code for approximately 7 kDa proteins, which differentially interact with specific ACD6 variants (see TC family 8.A.234). MHA1L enhances the accumulation of an ACD6 complex, thereby increasing the activity of the ACD6 standard allele for regulating plant growth and defenses. The intracellular ankyrin repeats of ACD6 are structurally similar to those found in mammalian ion channels. Increased ACD6 activity was linked to enhanced calcium channel-mediated influx, with MHA1L as a direct regulator of ACD6, indicating that peptide-regulated ion channels are not restricted to animals (Chen et al. 2023). Thus, some (but not all of the) evidence suggests that CTEPs are channel proteins.

References associated with 9.A.43 family:

Chen, J., L. Li, J.H. Kim, B. Neuhäuser, M. Wang, M. Thelen, R. Hilleary, Y. Chi, L. Wei, K. Venkataramani, M. Exposito-Alonso, C. Liu, J. Keck, A.C. Barragan, R. Schwab, U. Lutz, Z.M. Pei, S.Y. He, U. Ludewig, D. Weigel, and W. Zhu. (2023). Small proteins modulate ion-channel-like ACD6 to regulate immunity in Arabidopsis thaliana. Mol. Cell 83: 4386-4397.e9. 37995686
Jahrmann, T., M. Bastida, M. Pineda, E. Gasol, M.D. Ludevid, M. Palacín, and P. Puigdomènech. (2005). Studies on the function of TM20, a transmembrane protein present in cereal embryos. Planta 222: 80-90. 15838668
Kim, Y.Y., D.Y. Kim, D. Shim, W.Y. Song, J. Lee, J.I. Schroeder, S. Kim, N. Moran, and Y. Lee. (2008). Expression of the novel wheat gene TM20 confers enhanced cadmium tolerance to bakers' yeast. J. Biol. Chem. 283: 15893-15902. 18411273