Summary: Tetracyclin repressor-like, C-terminal domain
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Tetracyclin repressor-like, C-terminal domain Provide feedback
This family of bacterial transcriptional repressors is characterised by the short approximately 50 amino acid stretch of residues constituting the helix-turn-helix DNA binding motif, around the YRFhY motif. The target proteins that are repressed are involved in the transcriptional control of multi-drug efflux pumps, pathways for the biosynthesis of antibiotics, response to osmotic stress and toxic chemicals, control of catabolic pathways, differentiation processes, and pathogenicity .
Ramos JL, Martinez-Bueno M, Molina-Henares AJ, Teran W, Watanabe K, Zhang X, Gallegos MT, Brennan R, Tobes R;, Microbiol Mol Biol Rev. 2005;69:326-356. : The TetR family of transcriptional repressors. PUBMED:15944459 EPMC:15944459
Internal database links
|SCOOP:||TetR_C_10 TetR_C_13 TetR_C_15 TetR_C_16 TetR_C_17 TetR_C_2 TetR_C_21 TetR_C_24 TetR_C_25 TetR_C_27 TetR_C_29 TetR_C_31 TetR_C_33 TetR_C_4 TetR_C_5 TetR_C_6 TetR_C_7 TetR_C_9|
|Similarity to PfamA using HHSearch:||TetR_C_6 TetR_C_7 TetR_C_16|
This tab holds annotation information from the InterPro database.
InterPro entry IPR011075
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 [ PUBMED:16887689 , PUBMED:15837373 ]:
- 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 [ PUBMED:1423217 ]. 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 [ PUBMED:15944459 ]. 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.
This entry represents the C-terminal domain found in a number of different TetR transcription regulator proteins. TetR regulates the expression of the membrane-associated tetracycline resistance protein, TetA, which exports the tetracycline antibiotic out of the cell before it can attach to the ribosomes and inhibit protein synthesis [ PUBMED:7707374 ]. TetR blocks transcription from the genes encoding both TetA and TetR in the absence of antibiotic. The C-terminal domain is multi-helical and is interlocked in the homodimer with the helix-turn-helix (HTH) DNA-binding domain. Other members of the TetR family of transcriptional regulators carry this C-terminal domain. These include:
- QacR from Staphylococcus aureus, a multidrug binding protein that represses transcription of the qacA multidrug transporter gene [ PUBMED:11739955 ]
- Ethr, a repressor from Mycobacterium tuberculosis implicated in ethionamide drug resistance [ PUBMED:15236969 ]
- CprB, a gamma-butyrolactone autoregulator/receptor from Streptomyces coelicolor that acts as a DNA-binding protein [ PUBMED:14757054 ]
- YcdC, a hypothetical transcriptional regulator from Escherichia coli
- YsiA, YfiR, and YxaF, hypothetical transcriptional regulators from Bacillus subtilis
- YbiH, a hypothetical transcriptional regulator from Salmonella typhimurium
Below is a listing of the unique domain organisations or architectures in which this domain is found. More...
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This clan features families of transcriptional regulators for multidrug efflux pumps, which belong to the TetR superfamily. They are induced by the presence of a variety of factors, such as antibiotics or organic solvents. The C-terminal region featured in these families is thought to contain the inducer-binding site; the divergent sequences in this region allow for the binding of a variety of different inducers [1-4].
The clan contains the following 42 members:CecR_C COQ9 LuxT_C TetR TetR_C_1 TetR_C_10 TetR_C_11 TetR_C_12 TetR_C_13 TetR_C_14 TetR_C_15 TetR_C_16 TetR_C_17 TetR_C_18 TetR_C_19 TetR_C_2 TetR_C_20 TetR_C_21 TetR_C_22 TetR_C_23 TetR_C_24 TetR_C_25 TetR_C_26 TetR_C_27 TetR_C_28 TetR_C_29 TetR_C_3 TetR_C_30 TetR_C_31 TetR_C_32 TetR_C_33 TetR_C_34 TetR_C_35 TetR_C_36 TetR_C_37 TetR_C_38 TetR_C_4 TetR_C_5 TetR_C_6 TetR_C_7 TetR_C_8 TetR_C_9
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1Cannot generate PP/Heatmap alignments for seeds; no PP data available
Key: available, not generated, — not available.
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This page displays the phylogenetic tree for this family's seed alignment. We use FastTree to calculate neighbour join trees with a local bootstrap based on 100 resamples (shown next to the tree nodes). FastTree calculates approximately-maximum-likelihood phylogenetic trees from our seed alignment.
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|Number in seed:||294|
|Number in full:||7935|
|Average length of the domain:||111 aa|
|Average identity of full alignment:||21 %|
|Average coverage of the sequence by the domain:||54.67 %|
|HMM build commands:||
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 61295632 -E 1000 --cpu 4 HMM pfamseq
|Family (HMM) version:||8|
|Download:||download the raw HMM for this family|
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This visualisation provides a simple graphical representation of the distribution of this family across species. You can find the original interactive tree in the More....
This chart is a modified "sunburst" visualisation of the species tree for this family. It shows each node in the tree as a separate arc, arranged radially with the superkingdoms at the centre and the species arrayed around the outermost ring.
How the sunburst is generated
The tree is built by considering the taxonomic lineage of each sequence that has a match to this family. For each node in the resulting tree, we draw an arc in the sunburst. The radius of the arc, its distance from the root node at the centre of the sunburst, shows the taxonomic level ("superkingdom", "kingdom", etc). The length of the arc represents either the number of sequences represented at a given level, or the number of species that are found beneath the node in the tree. The weighting scheme can be changed using the sunburst controls.
In order to reduce the complexity of the representation, we reduce the number of taxonomic levels that we show. We consider only the following eight major taxonomic levels:
Colouring and labels
Segments of the tree are coloured approximately according to their superkingdom. For example, archeal branches are coloured with shades of orange, eukaryotes in shades of purple, etc. The colour assignments are shown under the sunburst controls. Where space allows, the name of the taxonomic level will be written on the arc itself.
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There are some situations that the sunburst tree cannot easily handle and for which we have work-arounds in place.
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Some species in the taxonomic tree may not have one or more of the main eight levels that we display. For example, Bos taurus is not assigned an order in the NCBI taxonomic tree. In such cases we mark the omitted level with, for example, "No order", in both the tooltip and the lineage summary.
Unmapped species names
The tree is built by looking at each sequence in the full alignment for the family. We take the name of the species given by UniProt and try to map that to the full taxonomic tree from NCBI. In some cases, the name chosen by UniProt does not map to any node in the NCBI tree, perhaps because the chosen name is listed as a synonym or a misspelling in the NCBI taxonomy.
So that these nodes are not simply omitted from the sunburst tree, we group them together in a separate branch (or segment of the sunburst tree). Since we cannot determine the lineage for these unmapped species, we show all levels between the superkingdom and the species as "uncategorised".
Since we reduce the species tree to only the eight main taxonomic levels, sequences that are mapped to the sub-species level in the tree would not normally be shown. Rather than leave out these species, we map them instead to their parent species. So, for example, for sequences belonging to one of the Vibrio cholerae sub-species in the NCBI taxonomy, we show them instead as belonging to the species Vibrio cholerae.
Too many species/sequences
For large species trees, you may see blank regions in the outer layers of the sunburst. These occur when there are large numbers of arcs to be drawn in a small space. If an arc is less than approximately one pixel wide, it will not be drawn and the space will be left blank. You may still be able to get some information about the species in that region by moving your mouse across the area, but since each arc will be very small, it will be difficult to accurately locate a particular species.
The tree shows the occurrence of this domain across different species. More...
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For all of the domain matches in a full alignment, we count the number that are found on all sequences in the alignment. This total is shown in the purple box.
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Finally, we group sequences from the same organism according to the NCBI code that is assigned by UniProt, allowing us to count the number of distinct sequences on which the domain is found. This value is shown in the pink boxes.
We use the NCBI species tree to group organisms according to their taxonomy and this forms the structure of the displayed tree. Note that in some cases the trees are too large (have too many nodes) to allow us to build an interactive tree, but in most cases you can still view the tree in a plain text, non-interactive representation. Those species which are represented in the seed alignment for this domain are highlighted.
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For those sequences which have a structure in the Protein DataBank, we use the mapping between UniProt, PDB and Pfam coordinate systems from the PDBe group, to allow us to map Pfam domains onto UniProt sequences and three-dimensional protein structures. The table below shows the structures on which the TetR_C_11 domain has been found. There are 10 instances of this domain found in the PDB. Note that there may be multiple copies of the domain in a single PDB structure, since many structures contain multiple copies of the same protein sequence.
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AlphaFold Structure Predictions
The list of proteins below match this family and have AlphaFold predicted structures. Click on the protein accession to view the predicted structure.