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2.A.35 The NhaC Na+:H+ Antiporter (NhaC) Family

Two members of the NhaC family have been functionally characterized. One is believed to be a Na+:H+ antiporter (Ito et al., 1997); the other is a malate · H+:lactate · Na+ antiporter (Wei et al., 2000). Several paralogues are found in Vibrio cholerae, and two paralogues each are found encoded in the completely sequenced genomes of Haemophilus influenzae and Bacillus subtilis. E. coli lacks such a homologue. Pyrococcus species also have at least one homologue each. Thus, members of the NhaC family are found in both Gram-negative bacteria and Gram-positive bacteria as well as archaea. NhaC of B. firmus is 462 amino acyl residues long and possesses 12 putative transmembrane α-helical segments. MleN of B. subtilis (468 aas) also exhibits 12 putative TMSs.

The transport reaction catalyzed by NhaC is probably:

Na+ (in) + nH+ (out) ⇌ Na+ (out) + nH+ (in). (n > 1)

That catalyzed by MleN is probably:

Malate (out) + H+ (out) + Lactate (in) + Na+ (in) ⇌ Malate (in) + H+ (in) + Lactate (out) + Na+ (out)


This family belongs to the: IT Superfamily.

References associated with 2.A.35 family:

Ito, M., A.A. Guffanti, J. Zemsky, D.M. Ivey, and T.A. Krulwich. (1997). Role of the nhaC-encoded Na+/H+ antiporter of alkaliphilic Bacillus firmus OF4. J. Bacteriol. 179: 3851-3857. 9190799
Ivey, D.M., A.A. Guffanti, J.S. Bossewitch, E. Padan, and T.A. Krulwich. (1991). Molecular cloning and sequencing of a gene from alkaliphilic Bacillus firmus OF4 that functionally complements an Escherichia coli strain carrying a deletion in the nhaA Na+/H+ antiporter gene. J. Biol. Chem. 266: 23484-23489. 1660475
Liew, C.W., R.M. Illias, N.M. Mahadi, and N. Najimudin. (2007). Expression of the Na+/H+ antiporter gene (g1-nhaC) of alkaliphilic Bacillus sp. G1 in Escherichia coli. FEMS Microbiol Lett. 276(1):114-122. 17937670
Panina, E.M., A.G. Vitreschak, A.A. Mironov, and M.S. Gelfand. (2003). Regulation of biosynthesis and transport of aromatic amino acids in low-GC Gram-positive bacteria. FEMS Microbiol. Lett. 222: 211-220. 12770710
Ravcheev, D.A., A.A. Best, N. Tintle, M. Dejongh, A.L. Osterman, P.S. Novichkov, and D.A. Rodionov. (2011). Inference of the transcriptional regulatory network in Staphylococcus aureus by integration of experimental and genomics-based evidence. J. Bacteriol. 193: 3228-3240. 21531804
Rodionov, D.A., A.G. Vitreschak, A.A. Mironov, and M.S. Gelfand. (2003). Regulation of lysine biosynthesis and transport genes in bacteria: yet another RNA riboswitch? Nucleic Acids Res 31: 6748-6757. 14627808
Rodionov, D.A., P. Hebbeln, A. Eudes, J. ter Beek, I.A. Rodionova, G.B. Erkens, D.J. Slotboom, M.S. Gelfand, A.L. Osterman, A.D. Hanson, and T. Eitinger. (2009). A novel class of modular transporters for vitamins in prokaryotes. J. Bacteriol. 191: 42-51. 18931129
Rodionov, D.A., P.S. Novichkov, E.D. Stavrovskaya, I.A. Rodionova, X. Li, M.D. Kazanov, D.A. Ravcheev, A.V. Gerasimova, A.E. Kazakov, G.Y. Kovaleva, E.A. Permina, O.N. Laikova, R. Overbeek, M.F. Romine, J.K. Fredrickson, A.P. Arkin, I. Dubchak, A.L. Osterman, and M.S. Gelfand. (2011). Comparative genomic reconstruction of transcriptional networks controlling central metabolism in the Shewanella genus. BMC Genomics 12Suppl1: S3. 21810205
Wei, Y., A.A. Guffanti, M. Ito, and T.A. Krulwich. (2000). Bacillus subtilis YqkI is a novel malic/Na+-lactate antiporter that enhances growth on malate at low protonmotive force. J. Biol. Chem. 275:30287-30292. 10903309
Wimmer, F., T. Oberwinkler, B. Bisle, J. Tittor, and D. Oesterhelt. (2008). Identification of the arginine/ornithine antiporter ArcD from Halobacterium salinarum. FEBS Lett. 582: 3771-3775. 18930051