InterPro : IPR001958

Name  Tetracycline resistance protein, TetA/multidrug resistance protein MdtG Short Name  Tet-R_TetA/multi-R_MdtG
Type  Family Description  The antibiotic tetracycline has a broad spectrum of activity, acting to inhibit bacterial protein synthesis by binding to the 30S ribosomal subunit, which prevents the association of the aminoacyl-tRNA to the ribosomal acceptor A site. Tetracycline binding is reversible, therefore diluting out the antibiotic can reverse its effects. Tetracycline resistance genes are often located on mobile elements, such as plasmids, transposons and/or conjugative transposons, which can sometimes be transferred between bacterial species. In certain cases, tetracycline can enhance the transfer of these elements, thereby promoting resistance amongst a bacterial colony. There are three types of tetracycline resistance: tetracycline efflux, ribosomal protection, and tetracycline modification [, ]: Tetracycline efflux proteins belong to the major facilitator superfamily. Efflux proteins are membrane-associated proteins that recognise and export tetracycline from the cell. They are found in both Gram-positive and Gram-negative bacteria []. There are at least 22 different tetracycline efflux proteins, grouped according to sequence similarity: Group 1 are Tet(A), Tet(B), Tet(C), Tet(D), Tet(E), Tet(G), Tet(H), Tet(J), Tet(Z) and Tet(30); Group 2 are Tet(K) and Tet(L); Group 3 are Otr(B) and Tcr(3); Group 4 is TetA(P); Group 5 is Tet(V). In addition, there are the efflux proteins Tet(31), Tet(33), Tet(V), Tet(Y), Tet(34), and Tet(35).Ribosomal protection proteins are cytoplasmic proteins that display homology with the elongation factors EF-Tu and EF-G. Protection proteins bind the ribosome, causing an alteration in ribosomal conformation that prevents tetracycline from binding. There are at least ten ribosomal protection proteins: Tet(M), Tet(O), Tet(S), Tet(W), Tet(32), Tet(36), Tet(Q), Tet(T), Otr(A), and TetB(P). Both Tet(M) and Tet(O) have ribosome-dependent GTPase activity, the hydrolysis of GTP providing the energy for the ribosomal conformational changes. Tetracycline modification proteins include the enzymes Tet(37) and Tet(X), both of which inactivate tetracycline. In addition, there are the tetracycline resistance proteins Tet(U) and Otr(C).The expression of several of these tet genes is controlled by a family of tetracycline transcriptional regulators known as TetR. TetR family regulators are involved in the transcriptional control of multidrug efflux pumps, pathways for the biosynthesis of antibiotics, response to osmotic stress and toxic chemicals, control of catabolic pathways, differentiation processes, and pathogenicity []. The TetR proteins identified in over 115 genera of bacteria and archaea share a common helix-turn-helix (HTH) structure in their DNA-binding domain. However, TetR proteins can work in different ways: they can bind a target operator directly to exert their effect (e.g. TetR binds Tet(A) gene to repress it in the absence of tetracycline), or they can be involved in complex regulatory cascades in which the TetR protein can either be modulated by another regulator or TetR can trigger the cellular response. The tetracycline resistance protein Tet(A) is a tetracycline efflux protein that functions as a metal-tetracycline/H+ antiporter [, ]. 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 [], 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 [].This entry also contains other members of the major facilitator family of drug extrusion translocases, like the multidrug resistance protein MdtG. MdtG is found in enterobacteria and confers resistance to fosfomycin and deoxycholate [].
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Sequence Features

GO Displayer

Proteins

InterPro protein domain ID --> Contigs

 

Other

1 Child Features

Id Name Short Name Type
IPR023692 Multidrug resistance protein MdtG Mutidrug-R_MdtG Family

0 Contains

0 Found In

1 Parent Features

Id Name Short Name Type
IPR011701 Major facilitator superfamily MFS Family

9 Publications

First Author Title Year Journal Volume Pages
Roberts MC Acquired tetracycline and/or macrolide-lincosamides-streptogramin resistance in anaerobes. 2003 Anaerobe 9 63-9
Roberts MC Update on acquired tetracycline resistance genes. 2005 FEMS Microbiol Lett 245 195-203
Speer BS Bacterial resistance to tetracycline: mechanisms, transfer, and clinical significance. 1992 Clin Microbiol Rev 5 387-99
Ramos JL The TetR family of transcriptional repressors. 2005 Microbiol Mol Biol Rev 69 326-56
Yamaguchi A Metal-tetracycline/H+ antiporter of Escherichia coli encoded by a transposon, Tn10. The role of the conserved dipeptide, Ser65-Asp66, in tetracycline transport. 1990 J Biol Chem 265 15525-30
Sapunaric FM Substitutions in the interdomain loop of the Tn10 TetA efflux transporter alter tetracycline resistance and substrate specificity. 2005 Microbiology 151 2315-22
Kimura T Roles of conserved arginine residues in the metal-tetracycline/H+ antiporter of Escherichia coli. 1998 Biochemistry 37 5475-80
Nishino K Analysis of a complete library of putative drug transporter genes in Escherichia coli. 2001 J Bacteriol 183 5803-12
Yamaguchi A Metal-tetracycline/H+ antiporter of Escherichia coli encoded by a transposon Tn10. Histidine 257 plays an essential role in H+ translocation. 1991 J Biol Chem 266 6045-51



To cite PlanMine, please refer to the following publication:

Rozanski, A., Moon, H., Brandl, H., Martín-Durán, J. M., Grohme, M., Hüttner, K., Bartscherer, K., Henry, I., & Rink, J. C.
PlanMine 3.0—improvements to a mineable resource of flatworm biology and biodiversity
Nucleic Acids Research, gky1070. doi:10.1093/nar/gky1070 (2018)