HTHR_MYCTU
ID HTHR_MYCTU Reviewed; 188 AA.
AC P9WMC3; L0TE16; P67442; Q50720;
DT 16-APR-2014, integrated into UniProtKB/Swiss-Prot.
DT 16-APR-2014, sequence version 1.
DT 25-MAY-2022, entry version 43.
DE RecName: Full=HTH-type transcriptional repressor Rv3405c {ECO:0000305};
GN OrderedLocusNames=Rv3405c; ORFNames=MTCY78.23;
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 IDENTIFICATION AS A DRUG TARGET [LARGE SCALE ANALYSIS].
RX PubMed=19099550; DOI=10.1186/1752-0509-2-109;
RA Raman K., Yeturu K., Chandra N.;
RT "targetTB: a target identification pipeline for Mycobacterium tuberculosis
RT through an interactome, reactome and genome-scale structural analysis.";
RL BMC Syst. Biol. 2:109-109(2008).
RN [3]
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 [4]
RP FUNCTION, AND INDUCTION.
RX PubMed=25427196; DOI=10.1021/cb5007163;
RA Neres J., Hartkoorn R.C., Chiarelli L.R., Gadupudi R., Pasca M.R., Mori G.,
RA Venturelli A., Savina S., Makarov V., Kolly G.S., Molteni E., Binda C.,
RA Dhar N., Ferrari S., Brodin P., Delorme V., Landry V.,
RA de Jesus Lopes Ribeiro A.L., Farina D., Saxena P., Pojer F., Carta A.,
RA Luciani R., Porta A., Zanoni G., De Rossi E., Costi M.P., Riccardi G.,
RA Cole S.T.;
RT "2-Carboxyquinoxalines kill Mycobacterium tuberculosis through noncovalent
RT inhibition of DprE1.";
RL ACS Chem. Biol. 10:705-714(2015).
RN [5]
RP FUNCTION, DNA-BINDING, ACTIVITY REGULATION, INDUCTION, DOMAIN, AND
RP MUTAGENESIS OF HIS-52; ARG-57 AND LYS-62.
RC STRAIN=H37Rv;
RX PubMed=29395080; DOI=10.1016/j.bbrc.2018.01.152;
RA Gopalan A., Bhagavat R., Chandra N., Subbarao S.H., Raja A.,
RA Bethunaickan R.;
RT "Biophysical and biochemical characterization of Rv3405c, a tetracycline
RT repressor protein from Mycobacterium tuberculosis.";
RL Biochem. Biophys. Res. Commun. 496:799-805(2018).
CC -!- FUNCTION: Negatively regulates the expression of sulfate ester
CC dioxygenase Rv3406 and its own expression (PubMed:25427196,
CC PubMed:29395080). Binds specifically to the inverted repeat sequence of
CC the intergenic region between Rv3405c and Rv3406 (PubMed:29395080).
CC {ECO:0000269|PubMed:25427196, ECO:0000269|PubMed:29395080}.
CC -!- ACTIVITY REGULATION: Specifically binds to tetracycline, which leads to
CC a conformational change in the structure of the protein and inhibits
CC the DNA binding activity. {ECO:0000269|PubMed:29395080}.
CC -!- INDUCTION: Negatively autoregulated. {ECO:0000269|PubMed:25427196,
CC ECO:0000269|PubMed:29395080}.
CC -!- DOMAIN: Contains an N-terminal DNA-binding domain and a C-terminal
CC ligand binding pocket. {ECO:0000269|PubMed:29395080}.
CC -!- MISCELLANEOUS: Was identified as a high-confidence drug target.
CC {ECO:0000269|PubMed:19099550}.
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DR EMBL; AL123456; CCP46227.1; -; Genomic_DNA.
DR PIR; B70736; B70736.
DR RefSeq; NP_217922.1; NC_000962.3.
DR RefSeq; WP_003417984.1; NZ_NVQJ01000027.1.
DR AlphaFoldDB; P9WMC3; -.
DR SMR; P9WMC3; -.
DR STRING; 83332.Rv3405c; -.
DR PaxDb; P9WMC3; -.
DR DNASU; 887940; -.
DR GeneID; 45427401; -.
DR GeneID; 887940; -.
DR KEGG; mtu:Rv3405c; -.
DR TubercuList; Rv3405c; -.
DR eggNOG; COG1309; Bacteria.
DR OMA; MRVWART; -.
DR PhylomeDB; P9WMC3; -.
DR Proteomes; UP000001584; Chromosome.
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:0006355; P:regulation of transcription, DNA-templated; IBA:GO_Central.
DR InterPro; IPR023772; DNA-bd_HTH_TetR-type_CS.
DR InterPro; IPR009057; Homeobox-like_sf.
DR InterPro; IPR001647; HTH_TetR.
DR Pfam; PF00440; TetR_N; 1.
DR PRINTS; PR00455; HTHTETR.
DR SUPFAM; SSF46689; SSF46689; 1.
DR PROSITE; PS01081; HTH_TETR_1; 1.
DR PROSITE; PS50977; HTH_TETR_2; 1.
PE 1: Evidence at protein level;
KW DNA-binding; Reference proteome; Repressor; Transcription;
KW Transcription regulation.
FT CHAIN 1..188
FT /note="HTH-type transcriptional repressor Rv3405c"
FT /id="PRO_0000070672"
FT DOMAIN 17..77
FT /note="HTH tetR-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00335"
FT DNA_BIND 40..59
FT /note="H-T-H motif"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00335"
FT MUTAGEN 52
FT /note="H->A: Abolishes DNA-binding and repressor activity;
FT when associated with A-57 and A-62."
FT /evidence="ECO:0000269|PubMed:29395080"
FT MUTAGEN 57
FT /note="R->A: Abolishes DNA-binding and repressor activity;
FT when associated with A-52 and A-62."
FT /evidence="ECO:0000269|PubMed:29395080"
FT MUTAGEN 62
FT /note="K->A: Abolishes DNA-binding and repressor activity;
FT when associated with A-52 and A-57."
FT /evidence="ECO:0000269|PubMed:29395080"
SQ SEQUENCE 188 AA; 20609 MW; 7B226876C5A43630 CRC64;
MTTRPATDRR KMPTGREEVA AAILQAATDL FAERGPAATS IRDIAARSKV NHGLVFRHFG
TKDQLVGAVL DHLGTKLTRL LHSEAPADII ERALDRHGRV LARALLDGYP VGQLQQRFPN
VAELLDAVRP RYDSDLGARL AVAHALALQF GWRLFAPMLR SATGIDELTG DELRLSVNDA
VARILEPH
