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2.A.76 The Resistance to Homoserine/Threonine (RhtB) Family

Hundreds of sequenced proteins, derived from Gram-negative and Gram-positive bacteria as well as archaea, comprise the RhtB family, but few of these proteins are functionally characterized (Vrljic et al., 1999). E. coli possesses five paralogues, and a large region of one of them (YahN of E. coli) exhibits significant sequence similiarity to YggA of E. coli, an established member of the LysE family (TC #2.A.75). The PSI-BLAST program groups the LysE family (TC# 2.A.75), the RhtB family and the CadD family (TC #2.A.77) together. These proteins are all of about the same size and apparent topology, further suggesting a common evolutionary origin.

The first two members of the RhtB family to be characterized functionally were the RhtB and RhtC permeases of E. coli (Aleshin et al., 1999; Zakataeva et al., 1999). YfiK of E. coli exports cysteine, O-acetylserine and azaserine (Franke et al., 2003). The YeaS (LeuE) homologue exports leucine and several other neutral, hydrophobic amino acids (Kutukova et al., 2005). Aleshin et al. (1999) present a partial alignment of recognized bacterial and archael members of the RhtB and LysE families, but not the CadD family. Vrljic et al. (1999) present phylogenetic trees for the original three families of the LysE superfamily (LysE, RhtB and CadD).

The transport reaction presumably catalyzed by members of the RhtB family is:

amino acid (in) + nH+ (out) ⇌ amino acid (out) + nH+ (in)

This family belongs to the: LysE Superfamily.

References associated with 2.A.76 family:

Aleshin, V.V., N.P. Zakataeva, and V.A. Livshits. (1999). A new family of amino acid efflux proteins. Trends Biochem. Sci. 24: 133-135. 10322417
Braun, S.D., J. Hofmann, A. Wensing, M.S. Ullrich, H. Weingart, B. Völksch, and D. Spiteller. (2010). Identification of the biosynthetic gene cluster for 3-methylarginine, a toxin produced by Pseudomonas syringae pv. syringae 22d/93. Appl. Environ. Microbiol. 76: 2500-2508. 20190091
Cegarra, C., C. Chaves, C. Déon, T.M. Do, B. Dumas, A. Frenzel, P. Kuhn, V. Roudieres, J.C. Guillemot, and D. Lesuisse. (2022). Exploring ITM2A as a new potential target for brain delivery. Fluids Barriers CNS 19: 25. 35313913
Franke, I., A. Resch, T. Dassler, T. Maier, and A. Bock. (2003). YfiK from Escherichia coli promotes export of O-acetylserine and cysteine. J. Bacteriol. 185: 1161-1166. 12562784
Franke, S., G. Grass, C. Rensing, and D.H. Nies. (2003). Molecular analysis of the copper-transporting efflux system CusCFBA of Escherichia coli. J. Bacteriol. 185: 3804-3812. 12813074
Hori, H., H. Yoneyama, R. Tobe, T. Ando, E. Isogai, and R. Katsumata. (2011). Inducible L-alanine exporter encoded by the novel gene ygaW (alaE) in Escherichia coli. Appl. Environ. Microbiol. 77: 4027-4034. 21531828
Kutukova, E.A., N.P. Zakataeva, and V.A. Livshits. (2005). [Expression of the genes encoding RhtB family proteins depends on global regulator Lrp]. Mol Biol (Mosk) 39: 374-378. 15981566
Kutukova, E.A., V.A. Livshits, I.P. Altman, L.R. Ptitsyn, M.H. Zyiatdinov, I.L. Tokmakova, and N.P. Zakataeva. (2005). The yeaS (leuE) gene of Escherichia coli encodes an exporter of leucine, and the Lrp protein regulates its expression. FEBS Lett. 579: 4629-4634. 16098526
Radi, M.S., J.E. SalcedoSora, S.H. Kim, S. Sudarsan, A.V. Sastry, D.B. Kell, M.J. Herrgård, and A.M. Feist. (2022). Membrane transporter identification and modulation via adaptive laboratory evolution. Metab Eng 72: 376-390. 35598887
Shimada, T., K. Tanaka, and A. Ishihama. (2016). Transcription factor DecR (YbaO) controls detoxification of L-cysteine in Escherichia coli. Microbiology 162: 1698-1707. 27435271
Ullrich, M. and C.L. Bender. (1994). The biosynthetic gene cluster for coronamic acid, an ethylcyclopropyl amino acid, contains genes homologous to amino acid-activating enzymes and thioesterases. J. Bacteriol. 176: 7574-7586. 8002582
Vicente, C.M., J. Santos-Aberturas, S.M. Guerra, T.D. Payero, J.F. Martín, and J.F. Aparicio. (2009). PimT, an amino acid exporter controls polyene production via secretion of the quorum sensing pimaricin-inducer PI-factor in Streptomyces natalensis. Microb Cell Fact 8: 33. 19505319
Vrljic, M., J. Garg, A. Bellman, S. Wachi, R. Freudl, M.J. Malecki, H. Sahm, V.J. Kozina, L. Eggeling, and M.H. Saier, Jr. (1999). The LysE superfamily: topology of the lysine exporter LysE of Corynebacterium glutamicum, a paradigm for a novel superfamily of transmembrane solute translocators. J. Mol. Microbiol. Biotechnol. 1: 327-336. 10943564
Zakataeva, N.P., V.V. Aleshin, I.L. Tokmakova, P.V. Troshin, and V.A. Livshits. (1999). The novel transmembrane Escherichia coli proteins involved in the amino acid efflux. FEBS Lett. 452: 228-232. 10386596