2.A.27 The Glutamate:Na+ Symporter (ESS) Family

Two members of this family have been functionally characterized. Both permeases (called GltS) have 401-402 amino acyl residues with 12 putative α-helical transmembrane spanners. Evidence for a 10 TMS topology has been obtained using translational lacZ and phoA fusions. Both hydrophobic segments that did not prove to be TMSs were glycine-rich (4 or 5 glycines per segment) (Gal et al., 2002). The two domains, of 5 TMSs plus a reentrant or pore-loop each, suggest that these proteins along with CitS in the 2HCT family, (2.A.24) might be members of the 2HCT superfamily (Dobrowolski et al., 2007). The occurrence of these 'helix breaking' residues may account for their exclusion from the membrane.

GltS is a Na+-dependent secondary carrier that transports L- and D-glutamate as well as the toxic analogues α-methyl glutamate and homocysteate (Essenberg, 1984). Homologues are found in many diverse Gram-negative proteobacteria, Synechocystis and Staphylococcus aureus. The family is thus widespread in bacteria but not in archaea or eukaryotes.

Dobrowolski and Lolkema (2009) have pointed to structural and mechanistic similarities between the ESS (TC #2.A.27) and 2-HCT (TC #2.A.24) transporters, as well as the two domain structure of the transporters and the presence and functional importance of the reentrant loops present in both domains. They propose that the conserved GGXG motifs are at the vertex of the reentrant loops.

The transport reaction catalyzed is:

glutamate (out) + Na+ (out) → glutamate (in) + Na+ (in)

This family belongs to the CPA Superfamily.



Boonburapong, B., S. Laloknam, N. Yamada, A. Incharoensakdi, and T. Takabe. (2012). Sodium-dependent uptake of glutamate by novel ApGltS enhanced growth under salt stress of halotolerant cyanobacterium Aphanothece halophytica. Biosci. Biotechnol. Biochem. 76: 1702-1707.

Chen, X., Y. Liu, J. Jin, H. Liu, Y. Hao, H. Zhang, and Y. Xie. (2021). YbfA Regulates the Sensitivity of K12 to Plantaricin BM-1 the BasS/BasR Two-Component Regulatory System. Front Microbiol 12: 659198.

Deguchi, Y., I. Yamato and Y. Anraku (1990). Nucleotide sequence of gltS, the Na+/glutamate symport carrier gene of Escherichia coli B. J. Biol. Chem. 265: 21704-21708.

Delprat, B., D. Schaer, S. Roy, J. Wang, J.L. Puel, and K. Geering. (2007). FXYD6 is a novel regulator of Na,K-ATPase expressed in the inner ear. J. Biol. Chem. 282: 7450-7456.

Dobrowolski, A. and J.S. Lolkema. (2010). Evolution of antiparallel two-domain membrane proteins. Swapping domains in the glutamate transporter GltS. Biochemistry 49: 5972-5974.

Dobrowolski, A., I. Sobczak-Elbourne, and J.S. Lolkema. (2007). Membrane topology prediction by hydropathy profile alignment: membrane topology of the Na+-glutamate transporter GltS. Biochemistry 46: 2326-2332.

Essenberg, R.C. (1984). Use of homocysteic acid for selecting mutants at the gltS locus of Escherichia coli K12. J. Gen. Microbiol. 130: 1311-1314.

Gál, J., A. Szvetnik and M. Kálmán (2002). Membrane topology of the GltS Na+/glutamate permease of Escherichia coli. J. Bacteriol., in press.

Quintero, M.J., M.L. Montesinos, A. Herrero and E. Flores (2001). Identification of genes encoding amino acid permeases by inactivation of selected ORFs from the Synechocystis genomic sequence. Genome Res., in press.

Reizer, J., A. Reizer and M.H. Saier, Jr. (1994). A functional superfamily of sodium/solute symporters. Biochim. Biophys. Acta 1197: 133-166.


TC#NameOrganismal TypeExample

Glutamate:Na+ symporter, GltS, of 401 aas and 12 TMSs.  It transports L- and D-glutamate, α-methylglutamate and homocysteate. Swapping the order of the two halves (repeat units) does not decrease activity (Dobrowolski and Lolkema, 2010).


GltS of E. coli (P0AER8)

2.A.27.1.2Glutamate:Na+ symporterCyanobacteriaGltS of Synechocystis PCC6803

Probable L-glutamate/N-acetylglutamate uptake porter, GltS.  Involved in N-acetylglutamate catabolism as a carbon and nitrogen source (Johnson et al. 2008).


GltS of Pseudomonas aereuginosa


Sodium/glutamate symporter, GltS, YbfA, JemA, of 401 aas and 12 TMSs. Note, the Na+:Glutamate symporter with TC# 2.A.27.1.1 is also called GltS. YbfA regulates the sensitivity of E. coli K12 to plantaricin BM-1 via the BasS/BasR two- component regulatory system (Chen et al. 2021).

GltS of E. coli


sodium:glutamate symporter of 476 aas and 12 TMSs, GltS. It has a Km for glutamate of 5 μM, but has low affinity for Na+. Glutamate uptake is inhibited by glu, gln, asp and asn (Boonburapong et al. 2012).



TC#NameOrganismal TypeExample

Glutamate:sodium symporter, GltS (Boonburapong et al. 2012).


GltS of Snyechococcus sp. ATCC27264 (Agmenellum guadruplicatum)


Archaeal GltS homologue


GltS of Methanosarcina mazei