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2.A.34 The NhaB Na+:H+ Antiporter (NhaB) Family

NhaB homologues are of 513 to 528 amino acyl residues in length and possess about 12 transmembrane α-helical spanners (TMSs). They exhibit a region with limited sequence similarity to a 46 Kd membrane protein of unknown function from Mycobacterium leprae (spP46838) which is homologous to a member of arsenate resistance pumps of bacteria, archaea and eukaryotes (TC #3.A.4). Only Gram-negative bacterial proteins have been functionally characterized.


The E. coli NhaB is 58% identical to the orthologous Vibrio alginolyticus Na+/H+ antiporter (Pinner et al., 1992). Although the latter protein is predicted to exhibit 10 TMSs, construction of NhaB-phoA fusions led to evidence for a 9 TMS model with the N-terminus in the cytoplasm and the C-terminus in the periplasm (Enomoto et al., 1998). A centrally located aspartyl residue in the 3rd TMS of the Vibrio alginolyticus homologue, conserved in all members of the family, has been shown to be essential for activity (Nakamura et al., 2001).

The generalized transport reaction catalyzed by NhaB of E. coli is:

2 Na+ (in) + 3 H+ (out) ⇌ 2 Na+ (out) + 3 H+ (in).


This family belongs to the: IT Superfamily.

References associated with 2.A.34 family:

Enomoto, H., T. Unemoto, M. Nishibuchi, E. Padan, and T. Nakamura. (1998). Topological study of the Vibrio alginolyticus Na+/H+ antiporter using gene fusions in Escherichia coli cells. Biochim. Biophys. Acta 1370: 77-86. 9518558
Nakamura, T., Y. Fujisaki, H. Enomoto, Y. Nakayama, T. Takabe, N. Yamaguchi, and N. Uozumi. (2001). Residue aspartate-147 from the third transmembrane region of Na+/H+ antiporter NhaB of Vibrio alginolyticus plays a role in its activity. J. Bacteriol. 183: 5762-5767. 11544242
Pinner, E., E. Padan, and S. Schuldiner. (1992). Cloning, sequencing and expression of the NhaB gene, encoding a Na+:H+ antiporter in Escherichia coli. J. Biol. Chem. 267: 11064-11068. 1317851
Radchenko, M.V., R. Waditee, S. Oshimi, M. Fukuhara, T. Takabe, and T. Nakamura. (2006). Cloning, functional expression and primary characterization of Vibrio parahaemolyticus K+/H+ antiporter genes in Escherichia coli. Mol. Microbiol. 59: 651-663. 16390457