2.A.62 The NhaD Na+:H+ Antiporter (NhaD) Family

The NhaD Na+/H+ antiporter has been characterized from two Vibrio species: V. parahaemolyticus and V. cholerae (Nozaki et al., 1998; Ostroumov et al., 2002) and in the haloalkaliphile, Alkalimonas amylolytica (Liu et al., 2005). These proteins and their homologues are 400-500 aas long and exhibit 10-13 TMSs. They catalyze Na+/H+ and Li+/H+ antiport. They exhibit activity at basic pH (8-10) with no activity at pH 7.5. The Amylolytica antiporter has low Na+ affinity and has optimal activity at 600 mM Na+. Homologues are found in proteobacteria of all groups, Flavobacteria and Chlamydia. Distant homologues of the IT superfamily are ubiquitous. The NhaD family is a constituent of the IT superfamily (Prakash et al., 2003).

The generalized reaction catalyzed by NhaD is:

nH+ (in) + mNa+ (out) ⇌ nH+ (out) + mNa+ (in).

(n and m are unknown, but are probably 1 or 2)

This family belongs to the IT Superfamily.



Barrero-Gil, J., A. Rodríguez-Navarro, and B. Benito. (2007). Cloning of the PpNHAD1 transporter of Physcomitrella patens, a chloroplast transporter highly conserved in photosynthetic eukaryotic organisms. J Exp Bot 58: 2839-2849.

Cui, Y., B. Cheng, Y. Meng, C. Li, H. Yin, P. Xu, and C. Yang. (2016). Expression and functional analysis of two NhaD type antiporters from the halotolerant and alkaliphilic Halomonas sp. Y2. Extremophiles 20: 631-639.

Kurz, M., A.N. Brünig, and E.A. Galinski. (2006). NhaD type sodium/proton-antiporter of Halomonas elongata: a salt stress response mechanism in marine habitats? Saline Systems 2: 10.

Liu, J., Y. Xue, Q. Wang, Y. Wei, T.H. Swartz, D.B. Hicks, M. Ito, Y. Ma, and T.A. Krulwich. (2005). The activity profile of the NhaD-type Na+(Li+)/H+ antiporter from the Soda Lake haloalkaliphile Alkalimonas amylolytica is adaptive for the extreme environment. J. Bacteriol. 187: 7589-7595.

Melo, A.M., N.A. Felix, J.N. Carita, L.M. Saraiva, and M. Teixeira. (2006). The Na+/H+ antiporter of the thermohalophilic bacterium Rhodothermus marinus. Biochem. Biophys. Res. Commun. 348: 1011-1017.

Nozaki, K., T. Kuroda, T. Mizushima, and T. Tsuchiya. (1998). A new Na+/H+ antiporter, NhaD, of Vibrio parahaemolyticus. Biochim. Biophys. Acta 1369: 213-220.

Ostroumov, E., J. Dzioba, P. Loewen, and P. Dibrov. (2002). Asp344 and Thr345 are critical for cation exchange mediated by NhaD, Na+/H+ antiporter of Vibrio cholerae. Biochim. Biophys. Acta 1564: 99-106.

Prakash, S., G. Cooper, S. Singhi, and M.H. Saier, Jr. (2003). The ion transporter superfamily. Biochim. Biophys. Acta 1618: 79-92.

Zhong, N.Q., L.B. Han, X.M. Wu, L.L. Wang, F. Wang, Y.H. Ma, and G.X. Xia. (2012). Ectopic expression of a bacterium NhaD-type Na+/H+ antiporter leads to increased tolerance to combined salt/alkali stresses. J Integr Plant Biol 54: 412-421.


TC#NameOrganismal TypeExample
2.A.62.1.1NhaD Na+/H+ antiporter Bacteria NhaD of Vibrio parahaemolyticus

NhaD Na+(Li+)/H+ antiporter (Liu et al., 2005).  AaNhaD is from the soda lake alkaliphile, Alkalimonas amylolytica, is crucial for the bacterium's resistance to salt/alkali stresses (Zhong et al. 2012).


NhaD of Alkalimonas amylolytica (AAX63482)


Chloroplast Na+/H+ antiporter of 582 aas, NhaD (Barrero-Gil et al. 2007).  Mediates ionic homeostasis in chloroplasts from red algae to flowering plants ((Barrero-Gil et al. 2007).


NhaD of Physcomitrella patens (Moss)


Na+/H+ antiporter, NhaD of 495 aas; involved in the response to salt stress and adaptation to a marine environment (Kurz et al. 2006).


NhaD of the halophilic eubacterium, Halomonas elongata


Sodium/proton antiporter, NhaD1, of 488 aas and 14 TMSs. Two NhaD homologues that catalyze Na+/H+ antiport were identified from this halotolerant and alkaliphilic strain isolated from sodium enriched black liquor. They exhibit 72% identity and have similar binding affinities for Na+ and Li+, while having different pH profiles. Ha-NhaD1 was active at pH 6.0 and most active at pH 8.0-8.5, whereas Ha-NhaD2 lacked activity at pH 6.0 but exhibited maximal activity at pH 9.5 or higher. Residues involved in transport were identified (Cui et al. 2016).

NhaD1 of Halomonas sp. Y2


Na+ or Li+/H+ antiporter, NhaD, of 477 aas and 14 TMSs.  It extrudes Na+ or Li+ in exchange for H+ (Dzioba et al. 2002).  Residues important for function have been identified (Ostroumov et al. 2002; Habibian et al. 2005). 

NhaD of Vibrio cholerae


NhaD homologue of 400 aas and 11 TMSs

NhaD of Hyphomicrobium zavarzinii