2.A.111 The Na^+/H⁺ Antiporter-E (NhaE) Family The NhaH family is a constituent of the IT superfamily (Lolkema and Slotboom 2003; Prakash et al. 2003; Rabus et al. 1999). It is the st321/AitJ family of Lolkema and Slotboom (2003). It consists of proteins from Gram-negative bacteria (e.g., Leptospira, Azotobacter, Neisseria, Ralstonia, Chlorobium and Rhizobial species). The proteins are of about 480 aas with 12-14 putative TMSs. An open reading frame from the genome of Neisseria meningitidis displaying similarity with the NhaE type of Na⁺/H⁺ antiporters was expressed in E. coli and characterized for sodium transport ability. The N. meningitidis antiporter (NmNhaE) was able to complement an E. coli strain devoid of Na⁺/H⁺ antiporters (KNabc) with respect to the ability to grow in the presence of high concentrations of NaCl or LiCl. Ion transport assays in everted vesicles prepared from the KNabc strain expressing NmNhaE from a plasmid confirmed its ability to translocate Na⁺ and Li⁺(Sousa et al. 2013). The generalized reaction catalyzed by NhaE is, Na⁺or Li⁺ (in) + H⁺ (out) ⇌ Na⁺ or Li⁺ (out) + H⁺ (in)
This family belongs to the IT Superfamily.
References:
Lolkema, J.S. and D.J. Slotboom. (2003). Classification of 29 families of secondary transport proteins into a single structural class using hydropathy profile analysis. J. Mol. Biol. 327: 901-909.
Melo, A.M., S.A. Lobo, F.L. Sousa, A.S. Fernandes, M.M. Pereira, G.O. Hreggvidsson, J.K. Kristjansson, L.M. Saraiva, and M. Teixeira. (2005). A nhaD Na⁺/H⁺ antiporter and a pcd homologues are among the Rhodothermus marinus complex I genes. Biochim. Biophys. Acta. 1709: 95-103.
Prakash, S., G. Cooper, S. Singhi, and M.H. Saier, Jr. (2003). The ion transporter superfamily. Biochim. Biophys. Acta. 1618: 79-92.
Rabus, R., D.L. Jack, D.J. Kelly, and M.H. Saier, Jr. (1999). TRAP transporters: an ancient family of extracytoplasmic solute-receptor-dependent secondary active transporters. Microbiology 145(Pt12): 3431-3445.
Sousa, P.M., M.A. Videira, T. Vorburger, S.T. Silva, J.W. Moir, J. Steuber, and A.M. Melo. (2013). The novel NhaE-type Na⁺/H (+) antiporter of the pathogenic bacterium Neisseria meningitidis. Arch. Microbiol. 195: 211-217.
Examples:
TC#	Name	Organismal Type	Example
2.A.111.1.1	Probable Na⁺/H⁺ antiporter, NhaE of 489 aa.	Spirochaetes	NhaE of Leptospira interrogans

2.A.111.1.2	*Na⁺/Li⁺/H⁺ antiporter, NhaE (Sousa et al.* 2013).**	β-Proteobacteria	NhaE of Neisseria meningitidis

2.A.111.1.3	*Na⁺/H⁺ antiporter, NhaD of 527 aas. Confers resistance to Na⁺, but not to Li⁺ (Melo et al.* 2005).**	Bacteroidetes	*NhaD of Rhodothermus marinus* (Q4QSA9)**

Examples:
TC#	Name	Organismal Type	Example
2.A.111.2.1	NhaE homologue of 428 aas and 12 TMSs PF07399; CL0182; IT superfamily).	Proteobacteria	NhaE homologue of Roseateles depolymerans

2.A.111.2.2	NhaE homologue of 450 aas and 11-12 TMSs.	Chlamydiae	NhaE homologue of Chlamydophila caviae