InterPro domain: IPR001958

The tetracycline resistance protein Tet(A) is a tetracycline efflux protein that functions as a metal-tetracycline/H+ antiporter [ 1 , 2 ]. This is an energy-dependent process that decreases the accumulation of the antibiotic in whole cells. Tet(A) is encoded by the transposon Tn10, and is an integral membrane protein with twelve potential transmembrane domains. Site-directed mutagenesis studies have shown that a negative charge at position 66 is essential for tetracycline transport [ 3 ], and that the region that includes the dipeptide plays an important role in metal-tetracycline transport; it perhaps acts as a gate that opens on the charge-charge interaction between Asp66 and the metal-tetracycline.The histidine at position 257 plays an essential role in H+ translocation [ 4 ].

Both TetA and MdtG belong to major facilitator superfamily (MFS), the largest and most diverse superfamily of secondary active transporters [ 5 ].

Multidrug resistance protein MdtG is found in enterobacteria and confers resistance to fosfomycin and deoxycholate [ 6 ].

1. Substitutions in the interdomain loop of the Tn10 TetA efflux transporter alter tetracycline resistance and substrate specificity. Microbiology (Reading, Engl.) 151, 2315-22
2. Roles of conserved arginine residues in the metal-tetracycline/H+ antiporter of Escherichia coli. Biochemistry 37, 5475-80
3. Metal-tetracycline/H+ antiporter of Escherichia coli encoded by a transposon, Tn10. The role of the conserved dipeptide, Ser65-Asp66, in tetracycline transport. J. Biol. Chem. 265, 15525-30
4. Metal-tetracycline/H+ antiporter of Escherichia coli encoded by a transposon Tn10. Histidine 257 plays an essential role in H+ translocation. J. Biol. Chem. 266, 6045-51
5. The major facilitator superfamily (MFS) revisited. FEBS J. 279, 2022-35
6. Analysis of a complete library of putative drug transporter genes in Escherichia coli. J. Bacteriol. 183, 5803-12