ETHR_MYCTU
ID ETHR_MYCTU Reviewed; 216 AA.
AC P9WMC1; L0TDZ6; P96222; Q7D4Q7;
DT 16-APR-2014, integrated into UniProtKB/Swiss-Prot.
DT 16-APR-2014, sequence version 1.
DT 03-AUG-2022, entry version 52.
DE RecName: Full=HTH-type transcriptional regulator EthR;
GN Name=ethR; Synonyms=etaR; OrderedLocusNames=Rv3855;
OS Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv).
OC Bacteria; Actinobacteria; Corynebacteriales; Mycobacteriaceae;
OC Mycobacterium; Mycobacterium tuberculosis complex.
OX NCBI_TaxID=83332;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=9634230; DOI=10.1038/31159;
RA Cole S.T., Brosch R., Parkhill J., Garnier T., Churcher C.M., Harris D.E.,
RA Gordon S.V., Eiglmeier K., Gas S., Barry C.E. III, Tekaia F., Badcock K.,
RA Basham D., Brown D., Chillingworth T., Connor R., Davies R.M., Devlin K.,
RA Feltwell T., Gentles S., Hamlin N., Holroyd S., Hornsby T., Jagels K.,
RA Krogh A., McLean J., Moule S., Murphy L.D., Oliver S., Osborne J.,
RA Quail M.A., Rajandream M.A., Rogers J., Rutter S., Seeger K., Skelton S.,
RA Squares S., Squares R., Sulston J.E., Taylor K., Whitehead S.,
RA Barrell B.G.;
RT "Deciphering the biology of Mycobacterium tuberculosis from the complete
RT genome sequence.";
RL Nature 393:537-544(1998).
RN [2]
RP FUNCTION AS A REPRESSOR OF ETHA, AND NOMENCLATURE.
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=10869356; DOI=10.1074/jbc.m003744200;
RA Baulard A.R., Betts J.C., Engohang-Ndong J., Quan S., McAdam R.A.,
RA Brennan P.J., Locht C., Besra G.S.;
RT "Activation of the pro-drug ethionamide is regulated in mycobacteria.";
RL J. Biol. Chem. 275:28326-28331(2000).
RN [3]
RP FUNCTION IN ETH RESISTANCE, AND NOMENCLATURE.
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=10944230; DOI=10.1073/pnas.97.17.9677;
RA DeBarber A.E., Mdluli K., Bosman M., Bekker L.G., Barry C.E. III;
RT "Ethionamide activation and sensitivity in multidrug-resistant
RT Mycobacterium tuberculosis.";
RL Proc. Natl. Acad. Sci. U.S.A. 97:9677-9682(2000).
RN [4]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=21969609; DOI=10.1074/mcp.m111.011627;
RA Kelkar D.S., Kumar D., Kumar P., Balakrishnan L., Muthusamy B., Yadav A.K.,
RA Shrivastava P., Marimuthu A., Anand S., Sundaram H., Kingsbury R.,
RA Harsha H.C., Nair B., Prasad T.S., Chauhan D.S., Katoch K., Katoch V.M.,
RA Kumar P., Chaerkady R., Ramachandran S., Dash D., Pandey A.;
RT "Proteogenomic analysis of Mycobacterium tuberculosis by high resolution
RT mass spectrometry.";
RL Mol. Cell. Proteomics 10:M111.011627-M111.011627(2011).
RN [5]
RP X-RAY CRYSTALLOGRAPHY (1.7 ANGSTROMS), AND SUBUNIT.
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=15236969; DOI=10.1016/j.jmb.2004.06.003;
RA Dover L.G., Corsino P.E., Daniels I.R., Cocklin S.L., Tatituri V.,
RA Besra G.S., Futterer K.;
RT "Crystal structure of the TetR/CamR family repressor Mycobacterium
RT tuberculosis EthR implicated in ethionamide resistance.";
RL J. Mol. Biol. 340:1095-1105(2004).
RN [6]
RP X-RAY CRYSTALLOGRAPHY (1.7 ANGSTROMS) IN COMPLEX WITH SUBSTRATE ANALOG,
RP ACTIVITY REGULATION, AND DISRUPTION PHENOTYPE.
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=19412174; DOI=10.1038/nm.1950;
RA Willand N., Dirie B., Carette X., Bifani P., Singhal A., Desroses M.,
RA Leroux F., Willery E., Mathys V., Deprez-Poulain R., Delcroix G.,
RA Frenois F., Aumercier M., Locht C., Villeret V., Deprez B., Baulard A.R.;
RT "Synthetic EthR inhibitors boost antituberculous activity of ethionamide.";
RL Nat. Med. 15:537-544(2009).
CC -!- FUNCTION: Involved in the repression of the monooxygenase EthA which is
CC responsible of the formation of the active metabolite of ethionamide
CC (ETH). {ECO:0000269|PubMed:10869356, ECO:0000269|PubMed:10944230}.
CC -!- ACTIVITY REGULATION: Inhibited by tert-butyl 4-(3-thiophen-2-yl-1,2,4-
CC oxadiazol-5-yl) piperidine-1-carboxylate (RF1) and 1-(thiophen-2-
CC ylacetyl)-4-(3-thiophen-2-yl-1,2,4-oxadiazol-5-yl)piperidine (RF3).
CC {ECO:0000269|PubMed:19412174}.
CC -!- SUBUNIT: Homodimer. {ECO:0000269|PubMed:15236969,
CC ECO:0000269|PubMed:19412174}.
CC -!- DISRUPTION PHENOTYPE: Cells lacking this gene leads to ETH
CC hypersentivity. {ECO:0000269|PubMed:19412174}.
CC -!- MISCELLANEOUS: Binding of inhibitors to EthR induces a conformational
CC change in this repressor, which is then unable to bind its DNA
CC operator, consequently allowing for increased transcription of EthA and
CC bioactivation of ethionamide (ETH).
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DR EMBL; AL123456; CCP46684.1; -; Genomic_DNA.
DR PIR; D70655; D70655.
DR RefSeq; NP_218372.1; NC_000962.3.
DR RefSeq; WP_003399797.1; NZ_NVQJ01000057.1.
DR PDB; 1T56; X-ray; 1.70 A; A=1-216.
DR PDB; 1U9N; X-ray; 2.30 A; A=2-216.
DR PDB; 1U9O; X-ray; 3.30 A; A/B=2-216.
DR PDB; 3G1L; X-ray; 1.70 A; A=1-216.
DR PDB; 3G1M; X-ray; 1.70 A; A=1-216.
DR PDB; 3G1O; X-ray; 1.85 A; A=1-216.
DR PDB; 3O8G; X-ray; 1.90 A; A=1-216.
DR PDB; 3O8H; X-ray; 1.90 A; A=1-216.
DR PDB; 3Q0U; X-ray; 1.70 A; A=1-216.
DR PDB; 3Q0V; X-ray; 1.95 A; A/B=1-216.
DR PDB; 3Q0W; X-ray; 1.60 A; A=1-216.
DR PDB; 3Q3S; X-ray; 2.00 A; A=1-216.
DR PDB; 3QPL; X-ray; 3.20 A; A=1-216.
DR PDB; 3SDG; X-ray; 1.87 A; A=1-216.
DR PDB; 3SFI; X-ray; 2.31 A; A=1-216.
DR PDB; 3TP0; X-ray; 1.90 A; A=1-216.
DR PDB; 3TP3; X-ray; 1.86 A; A=1-216.
DR PDB; 4DW6; X-ray; 2.00 A; A=1-216.
DR PDB; 4M3B; X-ray; 2.00 A; A=1-216.
DR PDB; 4M3D; X-ray; 1.90 A; A=1-216.
DR PDB; 4M3E; X-ray; 2.11 A; A=1-216.
DR PDB; 4M3G; X-ray; 2.30 A; A=1-216.
DR PDB; 5EYR; X-ray; 1.57 A; A=2-216.
DR PDB; 5EZG; X-ray; 1.84 A; A=2-216.
DR PDB; 5EZH; X-ray; 1.70 A; A=2-216.
DR PDB; 5F04; X-ray; 1.84 A; A=2-216.
DR PDB; 5F08; X-ray; 1.92 A; A=2-216.
DR PDB; 5F0C; X-ray; 1.87 A; A=2-216.
DR PDB; 5F0F; X-ray; 1.76 A; A=2-216.
DR PDB; 5F0H; X-ray; 1.99 A; A=2-216.
DR PDB; 5F1J; X-ray; 1.63 A; A=2-216.
DR PDB; 5F27; X-ray; 1.68 A; A=2-216.
DR PDB; 5J1R; X-ray; 1.92 A; A=1-216.
DR PDB; 5J1U; X-ray; 1.80 A; A=1-216.
DR PDB; 5J1Y; X-ray; 1.81 A; A=1-216.
DR PDB; 5J3L; X-ray; 1.66 A; A=1-216.
DR PDB; 5MWO; X-ray; 1.96 A; A=1-216.
DR PDB; 5MXK; X-ray; 1.93 A; A=1-216.
DR PDB; 5MXV; X-ray; 1.63 A; A=2-216.
DR PDB; 5MYL; X-ray; 1.72 A; A=1-216.
DR PDB; 5MYM; X-ray; 2.28 A; A/B/C/D=1-216.
DR PDB; 5MYN; X-ray; 1.56 A; A=1-216.
DR PDB; 5MYR; X-ray; 1.83 A; A=2-216.
DR PDB; 5MYS; X-ray; 1.59 A; A=2-216.
DR PDB; 5MYT; X-ray; 1.61 A; A=2-216.
DR PDB; 5MYW; X-ray; 1.77 A; A=2-216.
DR PDB; 5NIM; X-ray; 1.50 A; A=1-216.
DR PDB; 5NIO; X-ray; 1.40 A; A=1-216.
DR PDB; 5NIZ; X-ray; 1.95 A; A=1-216.
DR PDB; 5NJ0; X-ray; 2.10 A; A=1-216.
DR PDB; 5NZ0; X-ray; 1.82 A; A=2-216.
DR PDB; 5NZ1; X-ray; 2.33 A; A/B/C/D/E/F/G/H=2-216.
DR PDB; 6HO0; X-ray; 1.90 A; A=1-216.
DR PDB; 6HO4; X-ray; 1.60 A; A=1-216.
DR PDB; 6R1P; X-ray; 1.80 A; A=1-216.
DR PDB; 6R1S; X-ray; 1.80 A; A=1-216.
DR PDB; 7NGD; X-ray; 1.47 A; A=1-216.
DR PDB; 7NGG; X-ray; 1.17 A; C=1-216.
DR PDB; 7NGI; X-ray; 1.70 A; A=1-216.
DR PDB; 7NGJ; X-ray; 1.89 A; A=1-216.
DR PDB; 7NGK; X-ray; 1.89 A; A=1-216.
DR PDB; 7NGM; X-ray; 1.76 A; A=1-216.
DR PDB; 7NGN; X-ray; 1.55 A; A=1-216.
DR PDB; 7NGO; X-ray; 2.37 A; A=1-216.
DR PDB; 7NGR; X-ray; 1.92 A; A=1-216.
DR PDB; 7NGS; X-ray; 2.50 A; A=1-216.
DR PDB; 7NGT; X-ray; 2.49 A; A=1-216.
DR PDB; 7NGU; X-ray; 1.26 A; A=1-216.
DR PDB; 7NGW; X-ray; 1.26 A; A=1-216.
DR PDB; 7NGX; X-ray; 1.24 A; A=1-216.
DR PDB; 7NGY; X-ray; 1.27 A; A=1-216.
DR PDBsum; 1T56; -.
DR PDBsum; 1U9N; -.
DR PDBsum; 1U9O; -.
DR PDBsum; 3G1L; -.
DR PDBsum; 3G1M; -.
DR PDBsum; 3G1O; -.
DR PDBsum; 3O8G; -.
DR PDBsum; 3O8H; -.
DR PDBsum; 3Q0U; -.
DR PDBsum; 3Q0V; -.
DR PDBsum; 3Q0W; -.
DR PDBsum; 3Q3S; -.
DR PDBsum; 3QPL; -.
DR PDBsum; 3SDG; -.
DR PDBsum; 3SFI; -.
DR PDBsum; 3TP0; -.
DR PDBsum; 3TP3; -.
DR PDBsum; 4DW6; -.
DR PDBsum; 4M3B; -.
DR PDBsum; 4M3D; -.
DR PDBsum; 4M3E; -.
DR PDBsum; 4M3G; -.
DR PDBsum; 5EYR; -.
DR PDBsum; 5EZG; -.
DR PDBsum; 5EZH; -.
DR PDBsum; 5F04; -.
DR PDBsum; 5F08; -.
DR PDBsum; 5F0C; -.
DR PDBsum; 5F0F; -.
DR PDBsum; 5F0H; -.
DR PDBsum; 5F1J; -.
DR PDBsum; 5F27; -.
DR PDBsum; 5J1R; -.
DR PDBsum; 5J1U; -.
DR PDBsum; 5J1Y; -.
DR PDBsum; 5J3L; -.
DR PDBsum; 5MWO; -.
DR PDBsum; 5MXK; -.
DR PDBsum; 5MXV; -.
DR PDBsum; 5MYL; -.
DR PDBsum; 5MYM; -.
DR PDBsum; 5MYN; -.
DR PDBsum; 5MYR; -.
DR PDBsum; 5MYS; -.
DR PDBsum; 5MYT; -.
DR PDBsum; 5MYW; -.
DR PDBsum; 5NIM; -.
DR PDBsum; 5NIO; -.
DR PDBsum; 5NIZ; -.
DR PDBsum; 5NJ0; -.
DR PDBsum; 5NZ0; -.
DR PDBsum; 5NZ1; -.
DR PDBsum; 6HO0; -.
DR PDBsum; 6HO4; -.
DR PDBsum; 6R1P; -.
DR PDBsum; 6R1S; -.
DR PDBsum; 7NGD; -.
DR PDBsum; 7NGG; -.
DR PDBsum; 7NGI; -.
DR PDBsum; 7NGJ; -.
DR PDBsum; 7NGK; -.
DR PDBsum; 7NGM; -.
DR PDBsum; 7NGN; -.
DR PDBsum; 7NGO; -.
DR PDBsum; 7NGR; -.
DR PDBsum; 7NGS; -.
DR PDBsum; 7NGT; -.
DR PDBsum; 7NGU; -.
DR PDBsum; 7NGW; -.
DR PDBsum; 7NGX; -.
DR PDBsum; 7NGY; -.
DR AlphaFoldDB; P9WMC1; -.
DR SMR; P9WMC1; -.
DR STRING; 83332.Rv3855; -.
DR BindingDB; P9WMC1; -.
DR ChEMBL; CHEMBL1772929; -.
DR DrugBank; DB08471; 1-(thiophen-2-ylacetyl)-4-(3-thiophen-2-yl-1,2,4-oxadiazol-5-yl)piperidine.
DR DrugBank; DB08470; 3-(4-fluorophenyl)-5-phenyl-4H-1,2,4-triazole.
DR DrugBank; DB02425; Hexadecyl Octanoate.
DR DrugBank; DB08469; tert-butyl 4-(3-thiophen-2-yl-1,2,4-oxadiazol-5-yl)piperidine-1-carboxylate.
DR PaxDb; P9WMC1; -.
DR DNASU; 886189; -.
DR GeneID; 45427859; -.
DR GeneID; 886189; -.
DR KEGG; mtu:Rv3855; -.
DR TubercuList; Rv3855; -.
DR eggNOG; COG1309; Bacteria.
DR OMA; TLAHIWV; -.
DR PhylomeDB; P9WMC1; -.
DR PRO; PR:P9WMC1; -.
DR Proteomes; UP000001584; Chromosome.
DR GO; GO:0005829; C:cytosol; HDA:MTBBASE.
DR GO; GO:0003700; F:DNA-binding transcription factor activity; IBA:GO_Central.
DR GO; GO:0000976; F:transcription cis-regulatory region binding; IBA:GO_Central.
DR GO; GO:0045892; P:negative regulation of transcription, DNA-templated; IDA:MTBBASE.
DR GO; GO:0006355; P:regulation of transcription, DNA-templated; IBA:GO_Central.
DR GO; GO:0046677; P:response to antibiotic; IEP:MTBBASE.
DR InterPro; IPR009057; Homeobox-like_sf.
DR InterPro; IPR001647; HTH_TetR.
DR InterPro; IPR036271; Tet_transcr_reg_TetR-rel_C_sf.
DR Pfam; PF00440; TetR_N; 1.
DR PRINTS; PR00455; HTHTETR.
DR SUPFAM; SSF46689; SSF46689; 1.
DR SUPFAM; SSF48498; SSF48498; 1.
DR PROSITE; PS50977; HTH_TETR_2; 1.
PE 1: Evidence at protein level;
KW 3D-structure; DNA-binding; Reference proteome; Repressor; Transcription;
KW Transcription regulation.
FT CHAIN 1..216
FT /note="HTH-type transcriptional regulator EthR"
FT /id="PRO_0000398578"
FT DOMAIN 23..83
FT /note="HTH tetR-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00335"
FT DNA_BIND 46..65
FT /note="H-T-H motif"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00335"
FT REGION 1..24
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT SITE 176
FT /note="Inhibitor-binding"
FT SITE 179
FT /note="Inhibitor-binding"
FT HELIX 23..37
FT /evidence="ECO:0007829|PDB:5NIO"
FT HELIX 42..44
FT /evidence="ECO:0007829|PDB:5NIO"
FT HELIX 47..54
FT /evidence="ECO:0007829|PDB:5NIO"
FT HELIX 58..64
FT /evidence="ECO:0007829|PDB:5NIO"
FT HELIX 68..92
FT /evidence="ECO:0007829|PDB:5NIO"
FT HELIX 99..115
FT /evidence="ECO:0007829|PDB:5NIO"
FT HELIX 118..126
FT /evidence="ECO:0007829|PDB:5NIO"
FT HELIX 127..129
FT /evidence="ECO:0007829|PDB:5NIO"
FT HELIX 132..158
FT /evidence="ECO:0007829|PDB:5NIO"
FT HELIX 168..188
FT /evidence="ECO:0007829|PDB:5NIO"
FT HELIX 196..212
FT /evidence="ECO:0007829|PDB:5NIO"
SQ SEQUENCE 216 AA; 23757 MW; 129DEAB3320514B6 CRC64;
MTTSAASQAS LPRGRRTARP SGDDRELAIL ATAENLLEDR PLADISVDDL AKGAGISRPT
FYFYFPSKEA VLLTLLDRVV NQADMALQTL AENPADTDRE NMWRTGINVF FETFGSHKAV
TRAGQAARAT SVEVAELWST FMQKWIAYTA AVIDAERDRG AAPRTLPAHE LATALNLMNE
RTLFASFAGE QPSVPEARVL DTLVHIWVTS IYGENR
