2.A.134. The 3 TMS Na⁺/H⁺ antiporter, NhaM (NhaM) Family NhaM proteins are transmembrane proteins composed of about 103 amino acid residues that function as Na⁺(Li⁺, K⁺)/H⁺ antiporters (Shao et al. 2020). These antiporters are the smallest of known Na⁺/H⁺antiporters, and thus have been designated as NhaM to represent the minimal Na⁺/H⁺antiporter. Phylogenetic analysis and protein alignments have been reported. NhaM is assembled with parallel protomers into a homo-oligomer, and oligomerization is vital for the function of this antiporter. This implies that NhaM may adopt and require an oligomer for its normal function to create a similar X-shaped structure corresponding to that of the NhaA fold (Shao et al. 2020). Many of the NhaM homologues appear (based on hydrdopathy plots) to have 4 TMSs, often in a 2 + 2 TMS topology. This suggests either that a trimeric structure may be functional (assuming a 12 TMS topology, or if a tetramer is the active form, that it may have 16 TMSs. These proteins predominat in Firmcutes although homologs outside of this phylum have been detected, assuming that their annotated organismal assignments are correct.
References:
Shao, L., T. Xu, X. Zheng, D. Shao, H. Zhang, H. Chen, Z. Zhang, M. Yan, H. Abdel-Motaal, and J. Jiang. (2020). A novel three-TMH Na/H antiporter and the functional role of its oligomerization. J. Mol. Biol. 433: 166730. [Epub: Ahead of Print]
Examples:
TC#	Name	Organismal Type	Example
2.A.134.1.1	*Na⁺/K⁺/Li⁺:H⁺ antiporter, NhaM, of 89 aas and 2 or 3 TMSs/polypeptide chain. Four of these subunits may associate to make the complete transporter with ~12 TMSs (Shao et al.* 2020).**		NhaM of Halobacillus andaensis

2.A.134.1.10	Uncharacterized protein of 98 aas and probably 3 TMSs.		UP of Paenisporosarcina sp.

2.A.134.1.11	Uncharacterized protein of 102 aas and probably 3 TMSs in a 2 + 1 TMS arrangement.		UP of Bacillus paramycoides

2.A.134.1.13	Uncharacterized protein of 110 aas and 4 TMSs in a 1 + 1 + 2 TMS arrangement.		UP of Exiguobacterium chiriqhucha

2.A.134.1.14	Uncharacterized protein of 109 aas and 4 TMSs in a 2 + 2 TMS arrangement.		*UP of Gorillibacterium* sp. (glacier metagenome)**

2.A.134.1.15	Uncharacterized protein of 88 aas and 3 predicted TMSs.		UP of Candidatus Woesearchaeota archaeon (marine sediment metagenome)

2.A.134.1.16	Uncharacterized protein of 153 aas and 3 TMSs in a 2 + 1 arrangement.		UP of Lactobacillus florum

2.A.134.1.2	NhaM homologue of 129 aas and 4 TMSs.		NhaM of Staphylococcus aureus

2.A.134.1.3	Uncharacterized protein of 119 aas and 4 TMSs. May be a fragment.		*UP of Salmonella* sp.**

2.A.134.1.4	Uncharacterized protein of 106 aas and 3 or 4 TMSs.		UP of Halobacillus litoralis

2.A.134.1.5	Uncharacterized protein of 101 aas and 4 TMSs in a 2 + 2 TMS arrangement.		UP of Kurthia zopfii

2.A.134.1.6	Uncharacterized protein of 113 aas and 4 TMSs.		UP of Staphylococcus pseudintermedius

2.A.134.1.7	Uncharacterized protein of 131 aas and 3 or more likely 4 TMSs.		UP of Macrococcus brunensis

2.A.134.1.8	Uncharacterized protein of 126 aas and 3 TMSs		UP of Paenibacillus albus

2.A.134.1.9	Uncharacterized protein of 160 aas and probably 4 (maybe 3) TMSs.		*UP of Acinetobacter* sp.**

Examples:
TC#	Name	Organismal Type	Example
2.A.134.2.1	Uncharacterized protein of 113 aas and 4 TMSs in a 2 + 2 arrangement.		UP of Salipaludibacillus agaradhaerens

Examples:
TC#	Name	Organismal Type	Example
2.A.134.3.1	Uncharacterized protein of 141 aas and 4 TMSs		UP of Calidifontibacillus azotoformans

Examples:
TC#	Name	Organismal Type	Example
Examples:
TC#	Name	Organismal Type	Example
2.A.134.5.1	Uncharacterized protein of 196 aas and 3 TMSs.		UP of Oenococcus oeni