HTMR_MYCTU
ID HTMR_MYCTU Reviewed; 139 AA.
AC P9WME9; L0TCJ1; P67747; Q10810;
DT 16-APR-2014, integrated into UniProtKB/Swiss-Prot.
DT 16-APR-2014, sequence version 1.
DT 03-AUG-2022, entry version 42.
DE RecName: Full=HTH-type transcriptional repressor Rv2887 {ECO:0000305};
GN OrderedLocusNames=Rv2887; ORFNames=MTCY274.18;
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 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 [3]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RC STRAIN=H37Rv;
RX PubMed=26303802; DOI=10.1128/aac.01341-15;
RA Winglee K., Lun S., Pieroni M., Kozikowski A., Bishai W.;
RT "Mutation of Rv2887, a marR-like gene, confers Mycobacterium tuberculosis
RT resistance to an imidazopyridine-based agent.";
RL Antimicrob. Agents Chemother. 59:6873-6881(2015).
RN [4]
RP FUNCTION, DNA-BINDING, DISRUPTION PHENOTYPE, AND MUTAGENESIS OF ARG-81.
RC STRAIN=H37Rv;
RX PubMed=27432954; DOI=10.1073/pnas.1606590113;
RA Warrier T., Kapilashrami K., Argyrou A., Ioerger T.R., Little D.,
RA Murphy K.C., Nandakumar M., Park S., Gold B., Mi J., Zhang T., Meiler E.,
RA Rees M., Somersan-Karakaya S., Porras-De Francisco E., Martinez-Hoyos M.,
RA Burns-Huang K., Roberts J., Ling Y., Rhee K.Y., Mendoza-Losana A., Luo M.,
RA Nathan C.F.;
RT "N-methylation of a bactericidal compound as a resistance mechanism in
RT Mycobacterium tuberculosis.";
RL Proc. Natl. Acad. Sci. U.S.A. 113:E4523-E4530(2016).
RN [5] {ECO:0007744|PDB:5HSM, ECO:0007744|PDB:5HSO, ECO:0007744|PDB:5X7Z, ECO:0007744|PDB:5X80}
RP X-RAY CRYSTALLOGRAPHY (1.90 ANGSTROMS) OF APOPROTEIN AND IN COMPLEXES WITH
RP DNA; P-AMINOSALICYLIC ACID AND SALICYLIC ACID, FUNCTION, ACTIVITY
RP REGULATION, SUBUNIT, DOMAIN, AND MUTAGENESIS OF ARG-42 AND ASP-114.
RC STRAIN=H37Rv;
RX PubMed=28743871; DOI=10.1038/s41598-017-01705-4;
RA Gao Y.R., Li D.F., Fleming J., Zhou Y.F., Liu Y., Deng J.Y., Zhou L.,
RA Zhou J., Zhu G.F., Zhang X.E., Wang D.C., Bi L.J.;
RT "Structural analysis of the regulatory mechanism of MarR protein Rv2887 in
RT M. tuberculosis.";
RL Sci. Rep. 7:6471-6471(2017).
CC -!- FUNCTION: Represses expression of the HQNO methyltransferase htm gene
CC (Rv0560c) by binding to its promoter region (PubMed:26303802,
CC PubMed:27432954, PubMed:28743871). Also represses the expression of at
CC least five other genes, including the methyltransferase Rv0558
CC (PubMed:26303802). Binds salicylate (SA), para-aminosalicylic acid
CC (PAS) and gemfibrozil (PubMed:28743871). {ECO:0000269|PubMed:26303802,
CC ECO:0000269|PubMed:27432954, ECO:0000269|PubMed:28743871}.
CC -!- ACTIVITY REGULATION: Binding of effector molecule SA, or its structural
CC analog PAS, to the binding pocket of Rv2887 induces conformational
CC change in its DNA binding domain, preventing binding to the promoter
CC region of htm, triggering the expression of this SAM-dependent
CC methyltransferase. {ECO:0000269|PubMed:28743871}.
CC -!- SUBUNIT: Homodimer. {ECO:0000269|PubMed:28743871}.
CC -!- DOMAIN: Conformational changes take place in the N-terminal and the
CC winged-HTH (wHTH) domain on ligand or DNA binding. SA and PAS stabilize
CC a conformation of Rv2887 incompatible with DNA binding. Rotation of the
CC N-terminal plays a key role in the dimerization.
CC {ECO:0000269|PubMed:28743871}.
CC -!- DISRUPTION PHENOTYPE: Mutation of the gene leads to derepression and
CC increased expression of htm (PubMed:27432954). Inactivation of the gene
CC confers resistance to the imidazo[1,2-a]pyridine-4-carbonitrile-based
CC agent MP-III-71, an effective antimycobacterial compound that shows no
CC cross-resistance to existing antituberculosis drugs (PubMed:26303802).
CC {ECO:0000269|PubMed:26303802, ECO:0000269|PubMed:27432954}.
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DR EMBL; AL123456; CCP45689.1; -; Genomic_DNA.
DR PIR; B70925; B70925.
DR RefSeq; NP_217403.1; NC_000962.3.
DR RefSeq; WP_003899525.1; NZ_NVQJ01000006.1.
DR PDB; 5HSM; X-ray; 1.90 A; A=1-139.
DR PDB; 5HSO; X-ray; 2.50 A; A/B/C/D=1-139.
DR PDB; 5X7Z; X-ray; 2.20 A; A=1-139.
DR PDB; 5X80; X-ray; 2.40 A; A/B/C/D=1-139.
DR PDBsum; 5HSM; -.
DR PDBsum; 5HSO; -.
DR PDBsum; 5X7Z; -.
DR PDBsum; 5X80; -.
DR AlphaFoldDB; P9WME9; -.
DR SMR; P9WME9; -.
DR STRING; 83332.Rv2887; -.
DR PaxDb; P9WME9; -.
DR DNASU; 888563; -.
DR GeneID; 45426875; -.
DR GeneID; 888563; -.
DR KEGG; mtu:Rv2887; -.
DR TubercuList; Rv2887; -.
DR eggNOG; COG1846; Bacteria.
DR OMA; EFVCLRI; -.
DR PhylomeDB; P9WME9; -.
DR Proteomes; UP000001584; Chromosome.
DR GO; GO:0003677; F:DNA binding; IEA:UniProtKB-KW.
DR GO; GO:0003700; F:DNA-binding transcription factor activity; IEA:InterPro.
DR GO; GO:0006355; P:regulation of transcription, DNA-templated; IBA:GO_Central.
DR Gene3D; 1.10.10.10; -; 1.
DR InterPro; IPR000835; HTH_MarR-typ.
DR InterPro; IPR023187; Tscrpt_reg_MarR-type_CS.
DR InterPro; IPR036388; WH-like_DNA-bd_sf.
DR InterPro; IPR036390; WH_DNA-bd_sf.
DR Pfam; PF01047; MarR; 1.
DR PRINTS; PR00598; HTHMARR.
DR SMART; SM00347; HTH_MARR; 1.
DR SUPFAM; SSF46785; SSF46785; 1.
DR PROSITE; PS01117; HTH_MARR_1; 1.
DR PROSITE; PS50995; HTH_MARR_2; 1.
PE 1: Evidence at protein level;
KW 3D-structure; DNA-binding; Reference proteome; Repressor; Transcription;
KW Transcription regulation.
FT CHAIN 1..139
FT /note="HTH-type transcriptional repressor Rv2887"
FT /id="PRO_0000054410"
FT DOMAIN 6..138
FT /note="HTH marR-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00345"
FT BINDING 42
FT /ligand="salicylate"
FT /ligand_id="ChEBI:CHEBI:30762"
FT /evidence="ECO:0000269|PubMed:28743871"
FT BINDING 114
FT /ligand="salicylate"
FT /ligand_id="ChEBI:CHEBI:30762"
FT /evidence="ECO:0000269|PubMed:28743871"
FT MUTAGEN 42
FT /note="R->A: Attenuates the ability to bind salicylate."
FT /evidence="ECO:0000269|PubMed:28743871"
FT MUTAGEN 81
FT /note="R->Q: Abolishes binding to Rv0560c promoter."
FT /evidence="ECO:0000269|PubMed:27432954"
FT MUTAGEN 114
FT /note="D->A: Attenuates the ability to bind salicylate."
FT /evidence="ECO:0000269|PubMed:28743871"
FT TURN 2..4
FT /evidence="ECO:0007829|PDB:5HSM"
FT HELIX 8..28
FT /evidence="ECO:0007829|PDB:5HSM"
FT HELIX 29..31
FT /evidence="ECO:0007829|PDB:5HSM"
FT HELIX 35..46
FT /evidence="ECO:0007829|PDB:5HSM"
FT STRAND 47..49
FT /evidence="ECO:0007829|PDB:5X7Z"
FT HELIX 52..58
FT /evidence="ECO:0007829|PDB:5HSM"
FT HELIX 63..75
FT /evidence="ECO:0007829|PDB:5HSM"
FT STRAND 78..80
FT /evidence="ECO:0007829|PDB:5X7Z"
FT STRAND 85..88
FT /evidence="ECO:0007829|PDB:5X80"
FT HELIX 97..118
FT /evidence="ECO:0007829|PDB:5HSM"
FT HELIX 123..136
FT /evidence="ECO:0007829|PDB:5HSM"
SQ SEQUENCE 139 AA; 14690 MW; EB775A4CC03A24C0 CRC64;
MGLADDAPLG YLLYRVGAVL RPEVSAALSP LGLTLPEFVC LRMLSQSPGL SSAELARHAS
VTPQAMNTVL RKLEDAGAVA RPASVSSGRS LPATLTARGR ALAKRAEAVV RAADARVLAR
LTAPQQREFK RMLEKLGSD
