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:

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.

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.

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.

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.

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.

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.

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.

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.

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.

Shimada, T., K. Tanaka, and A. Ishihama. (2016). Transcription factor DecR (YbaO) controls detoxification of L-cysteine in Escherichia coli. Microbiology 162: 1698-1707.

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.

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.

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.

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.

Examples:

TC#NameOrganismal TypeExample
2.A.76.1.1

Homoserine/homoserine lactone/β-hydroxynorvaline efflux permease (probable substrate:H+ antiporter), RhtB (YigK).  Expression is under the control of the leucine-responsive protein, Lrp, and amino acids in the medium (Kutukova et al. 2005).

Bacteria

RhtB of E. coli (P0AG34)

 
2.A.76.1.10

RhtB family porter of 210 aas and 6 TMSs.  Based on homology, may export serine, threonine, homoserine and/or homoserine lactones.  Possibly regulated by a LysR transcription factor.  The gene maps adjacent to a probable heterodimeric DMT superfamily transporter (2.A.7.21.5).

Proteobacteria

RhtB family homologue of Klebsiella oxytoca

 
2.A.76.1.11

Amino acid exporter of 210 aas and 6 TMSs, MrsC.  Encoded by the mrsC gene in an operon for the biosynthesis of the toxic amino acid analogue, 3-methyarginine, the likely substrate (Braun et al. 2010).  The epiphytic Pseudomonas syringae strain which produces and excretes 3-methyarginine does so to compete with pathogenic strains of P. syringae for which 3-methyarginine is toxic.

Proteobacteria

MrsC of Pseudomonas syringae

 
2.A.76.1.12

Uncharacterized amino acid transporter of 207 aas and 6 TMSs.

UP of Candidatus Wolfebacteria bacterium

 
2.A.76.1.13

LysE superfamily member of 220 aas and 6 TMSs in a 3 + 3 arrangement

LysE member of Lokiarchaeum sp. GC14_75 (from a marine sediment metagenome)

 
2.A.76.1.2

Threonine efflux permease (probable threonine:H+ antiporter), RhtC (YigJ).  Expression is under the control of the leucine-responsive protein, Lrp, and amino acids in the medium (Kutukova et al. 2005). Mutation of the rhtC gene can protect cells against toxic levels of threonine (Radi et al. 2022).

Bacteria

RhtC (YigJ) of E. coli (P0AG38)

 
2.A.76.1.3

Probable amino acid exporter, YahN or YhaM, of 233 aas and 6 TMSs.  Expression is under the control of the leucine-responsive protein, Lrp, and amino acids in the medium (Kutukova et al. 2005). The yahOM operon is induced by cysteine where the cysteine sensor is the DecR/YbaO protein, and this operon is involved in L-cysteine detoxification (Shimada et al. 2016).

Bacteria

YahN of E. coli (P75693)

 
2.A.76.1.4

O-aetylserine/cysteine/azaserine exporter, EamB or YfiK of 195 aas and 6 TMSs (Franke et al., 2003).  High level cell-free expression and specific labeling of EamB of E. coli has been achieved (Klammt et al. 2004). 

Bacteria

EamB or YfiK of E. coli

 
2.A.76.1.5

The leucine exporter (LeuE; YeaS) (binds and probably transports L-methionine, L-histidine, L-α-amino-n-butyrate, norleucine, azaleucine, S(2-aminoethyl)-L-cysteine, 3,4-dehydro-DL-proline, L-alanine, and both D- and L-valine) (Kutukova et al., 2005; Hori et al., 2011; Radi et al. 2022).  Expression is under the control of the leucine-responsive protein, Lrp, and amino acids in the medium (Kutukova et al. 2005). Mutation of the leuE gene allows tolerance to high levels of histidine, presumably by allowing histidine efflux (Radi et al. 2022).

Bacteria

LeuE of E. coli (P76249)

 
2.A.76.1.6

The RhtB family member, RSP_2720

Bacteria

RSP_2070 of Rhodobacter sphaeroides (Q3J2V9)

 
2.A.76.1.7

Putative amino acid exporter of 208 aas; RhtB family member; similar to 2.A.76.1.5.

Firmicutes

RhtB family member of Bacillus subtilis

 
2.A.76.1.8

Putative amino acid efflux porter of 210 aas, YrhP.  Most similar to 2.A.76.1.5 of the characterized proteins in TCDB.

Firmicutes

YrhP of Bacillus subtilis

 
2.A.76.1.9

Exporter for L-homoserine, L-serine, and L-homoserine lactone as well as the quorum-sensing pimaricin-inducer PI-factor (2,3-diamino-2,3-bis(hydroxymethyl)-1,4-butanediol), PimT (Vicente et al. 2009).

Actinobacteria

PimT of Streptomyces natalensis

 
Examples:

TC#NameOrganismal TypeExample
2.A.76.2.1

Potential coronamic acid exporter of 236 aas and 5 TMSs.  Coronamic acid (CMA), an ethylcyclopropyl amino acid derived from isoleucine, functions as an intermediate in the biosynthesis of coronatine, a chlorosis-inducing phytotoxin produced by Pseudomonas syringae pv. glycinea PG4180. The DNA required for CMA biosynthesisincludes three distinct open reading frames (ORFs) which share a common orientation for transcription.  Two ORFs in the operon include CmaT, a thioesterase and CmaU, a potential exporter (Ullrich and Bender 1994).

Proteobacteria

CmaU of Pseudomonas syringae

 
2.A.76.2.2

CmaU of 203 aas and 5 or 6 TMSs.  This protein resembles 2.A.76.2.1; one or the other may be an incomplete or inaccurate sequence.

Proteobacteria

CmaU of Pseudomonas syringae

 
2.A.76.2.3

CmaU homologue of 203 aas and 6 TMSs.

Protobacteria

CmaU of Achromobacter xylosoxidans

 
Examples:

TC#NameOrganismal TypeExample
2.A.76.3.1

Uncharacterized probable amino acid exporter of 230 aas and 6 TMSs.

UP of Croceibacter atlanticus