NEMR_ECOLI
ID NEMR_ECOLI Reviewed; 199 AA.
AC P67430; P76189; Q2MB64;
DT 11-OCT-2004, integrated into UniProtKB/Swiss-Prot.
DT 11-OCT-2004, sequence version 1.
DT 03-AUG-2022, entry version 128.
DE RecName: Full=HTH-type transcriptional repressor NemR {ECO:0000305};
DE AltName: Full=Bleach-sensing transcription factor {ECO:0000303|PubMed:23536188};
DE AltName: Full=Redox-regulated transcription factor NemR {ECO:0000305};
GN Name=nemR {ECO:0000303|PubMed:18567656}; Synonyms=ydhM;
GN OrderedLocusNames=b1649, JW5874;
OS Escherichia coli (strain K12).
OC Bacteria; Proteobacteria; Gammaproteobacteria; Enterobacterales;
OC Enterobacteriaceae; Escherichia.
OX NCBI_TaxID=83333;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=K12 / MG1655 / ATCC 47076;
RX PubMed=9278503; DOI=10.1126/science.277.5331.1453;
RA Blattner F.R., Plunkett G. III, Bloch C.A., Perna N.T., Burland V.,
RA Riley M., Collado-Vides J., Glasner J.D., Rode C.K., Mayhew G.F.,
RA Gregor J., Davis N.W., Kirkpatrick H.A., Goeden M.A., Rose D.J., Mau B.,
RA Shao Y.;
RT "The complete genome sequence of Escherichia coli K-12.";
RL Science 277:1453-1462(1997).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=K12 / W3110 / ATCC 27325 / DSM 5911;
RX PubMed=16738553; DOI=10.1038/msb4100049;
RA Hayashi K., Morooka N., Yamamoto Y., Fujita K., Isono K., Choi S.,
RA Ohtsubo E., Baba T., Wanner B.L., Mori H., Horiuchi T.;
RT "Highly accurate genome sequences of Escherichia coli K-12 strains MG1655
RT and W3110.";
RL Mol. Syst. Biol. 2:E1-E5(2006).
RN [3]
RP FUNCTION, DNA-BINDING, ACTIVITY REGULATION, AND INDUCTION.
RC STRAIN=K12 / W3110 / ATCC 27325 / DSM 5911;
RX PubMed=18567656; DOI=10.1128/jb.00459-08;
RA Umezawa Y., Shimada T., Kori A., Yamada K., Ishihama A.;
RT "The uncharacterized transcription factor YdhM is the regulator of the nemA
RT gene, encoding N-ethylmaleimide reductase.";
RL J. Bacteriol. 190:5890-5897(2008).
RN [4]
RP FUNCTION, ACTIVITY REGULATION, AND DISULFIDE BOND.
RC STRAIN=K12;
RX PubMed=23506073; DOI=10.1111/mmi.12192;
RA Lee C., Shin J., Park C.;
RT "Novel regulatory system nemRA-gloA for electrophile reduction in
RT Escherichia coli K-12.";
RL Mol. Microbiol. 88:395-412(2013).
RN [5]
RP FUNCTION, ACTIVITY REGULATION, INDUCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=23536188; DOI=10.1074/jbc.m113.454421;
RA Gray M.J., Wholey W.Y., Parker B.W., Kim M., Jakob U.;
RT "NemR is a bleach-sensing transcription factor.";
RL J. Biol. Chem. 288:13789-13798(2013).
RN [6]
RP FUNCTION.
RX PubMed=23646895; DOI=10.1111/mmi.12234;
RA Ozyamak E., de Almeida C., de Moura A.P., Miller S., Booth I.R.;
RT "Integrated stress response of Escherichia coli to methylglyoxal:
RT transcriptional readthrough from the nemRA operon enhances protection
RT through increased expression of glyoxalase I.";
RL Mol. Microbiol. 88:936-950(2013).
RN [7] {ECO:0007744|PDB:4YZE}
RP X-RAY CRYSTALLOGRAPHY (2.20 ANGSTROMS), AND SULFENAMIDE BOND.
RX PubMed=25867078; DOI=10.1089/ars.2015.6346;
RA Gray M.J., Li Y., Leichert L.I., Xu Z., Jakob U.;
RT "Does the transcription factor NemR use a regulatory sulfenamide bond to
RT sense bleach?";
RL Antioxid. Redox Signal. 23:747-754(2015).
CC -!- FUNCTION: Involved in response to both electrophiles and reactive
CC chlorine species (RCS) (PubMed:23506073, PubMed:23536188). Represses
CC the transcription of the nemRA-gloA operon by binding to the NemR box
CC (PubMed:18567656, PubMed:23506073, PubMed:23536188). May sense
CC electrophiles, primarily quinones and glyoxals, as redox signals and
CC regulate the redox state by modulating the expression of nemA and gloA
CC (PubMed:23506073). Also uses the oxidation status of HOCl-sensitive
CC cysteine residues to respond to bleach and related RCS
CC (PubMed:23536188). Involved in response to methylglyoxal
CC (PubMed:23646895). {ECO:0000269|PubMed:18567656,
CC ECO:0000269|PubMed:23506073, ECO:0000269|PubMed:23536188,
CC ECO:0000269|PubMed:23646895}.
CC -!- ACTIVITY REGULATION: The redox state of the cysteines plays a crucial
CC role in the regulation of NemR activity (PubMed:23506073,
CC PubMed:23536188). Inactivated by reversible oxidation of cysteine
CC residues in the presence of inducers such as quinones, glyoxals and
CC reactive chlorine species (PubMed:23506073, PubMed:23536188). Also
CC irreversibly inactivated by alkylation in the presence of N-
CC ethylmaleimide (NEM) and other Cys modification reagents
CC (PubMed:18567656). Inactivation by inducers decreases DNA-binding
CC affinity and leads to the derepression of the nemRA-gloA operon
CC (PubMed:18567656, PubMed:23506073, PubMed:23536188).
CC {ECO:0000269|PubMed:18567656, ECO:0000269|PubMed:23506073,
CC ECO:0000269|PubMed:23536188}.
CC -!- INTERACTION:
CC P67430; P04951: kdsB; NbExp=3; IntAct=EBI-544803, EBI-544810;
CC -!- INDUCTION: Autoregulated (PubMed:18567656). Up-regulated by
CC hypochlorous acid (HOCl), the active component of household bleach
CC (PubMed:23536188). {ECO:0000269|PubMed:18567656,
CC ECO:0000269|PubMed:23536188}.
CC -!- PTM: Cys-21 and Cys-116 form reversible intermolecular disulfide bonds
CC in the presence of reactive electrophilic species (RES). Formation of
CC disulfide bonds leads to dimerization of NemR, which alters DNA binding
CC affinity and NemR activity. {ECO:0000269|PubMed:23506073}.
CC -!- PTM: Oxidized on Cys-106. Reversible oxidative modification of Cys-106
CC plays the central role in the sensing of and response to bleach and
CC other RCS (PubMed:23536188). It leads to the formation of a reversible
CC sulfenamide bond between Cys-106 and Lys-175 (PubMed:25867078).
CC Oxidation alters DNA binding affinity and NemR activity
CC (PubMed:23536188). {ECO:0000269|PubMed:23536188,
CC ECO:0000269|PubMed:25867078}.
CC -!- DISRUPTION PHENOTYPE: Deletion mutant is more resistant to
CC methylglyoxal than wild-type strain. {ECO:0000269|PubMed:23536188}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAE76492.1; Type=Erroneous initiation; Evidence={ECO:0000305};
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DR EMBL; U00096; AAC74721.3; -; Genomic_DNA.
DR EMBL; AP009048; BAE76492.1; ALT_INIT; Genomic_DNA.
DR PIR; C64922; C64922.
DR RefSeq; NP_416166.3; NC_000913.3.
DR RefSeq; WP_001032936.1; NZ_STEB01000003.1.
DR PDB; 4YZE; X-ray; 2.20 A; A/B/C/D=1-199.
DR PDBsum; 4YZE; -.
DR AlphaFoldDB; P67430; -.
DR SMR; P67430; -.
DR BioGRID; 4260266; 2.
DR BioGRID; 850526; 1.
DR DIP; DIP-48165N; -.
DR IntAct; P67430; 1.
DR STRING; 511145.b1649; -.
DR jPOST; P67430; -.
DR PaxDb; P67430; -.
DR PRIDE; P67430; -.
DR DNASU; 946166; -.
DR EnsemblBacteria; AAC74721; AAC74721; b1649.
DR EnsemblBacteria; BAE76492; BAE76492; BAE76492.
DR GeneID; 66674459; -.
DR GeneID; 946166; -.
DR KEGG; ecj:JW5874; -.
DR KEGG; eco:b1649; -.
DR PATRIC; fig|1411691.4.peg.610; -.
DR EchoBASE; EB3705; -.
DR eggNOG; COG1309; Bacteria.
DR HOGENOM; CLU_069356_28_1_6; -.
DR InParanoid; P67430; -.
DR OMA; CAQTIYT; -.
DR PhylomeDB; P67430; -.
DR BioCyc; EcoCyc:G6889-MON; -.
DR PRO; PR:P67430; -.
DR Proteomes; UP000000318; Chromosome.
DR Proteomes; UP000000625; Chromosome.
DR GO; GO:0003677; F:DNA binding; IEA:UniProtKB-KW.
DR GO; GO:0003700; F:DNA-binding transcription factor activity; IDA:EcoCyc.
DR GO; GO:0045892; P:negative regulation of transcription, DNA-templated; IDA:EcoCyc.
DR InterPro; IPR009057; Homeobox-like_sf.
DR InterPro; IPR001647; HTH_TetR.
DR InterPro; IPR036271; Tet_transcr_reg_TetR-rel_C_sf.
DR InterPro; IPR011075; TetR_C.
DR Pfam; PF16925; TetR_C_13; 1.
DR Pfam; PF00440; TetR_N; 1.
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; Disulfide bond; DNA-binding; Reference proteome; Repressor;
KW Stress response; Transcription; Transcription regulation.
FT CHAIN 1..199
FT /note="HTH-type transcriptional repressor NemR"
FT /id="PRO_0000070639"
FT DOMAIN 7..67
FT /note="HTH tetR-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00335"
FT DNA_BIND 30..49
FT /note="H-T-H motif"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00335"
FT SITE 106
FT /note="Plays a central role in response to RCS"
FT /evidence="ECO:0000269|PubMed:23536188,
FT ECO:0000269|PubMed:25867078"
FT DISULFID 21
FT /note="Interchain; in the presence of RES; transient"
FT /evidence="ECO:0000269|PubMed:23506073"
FT DISULFID 116
FT /note="Interchain; in the presence of RES; transient"
FT /evidence="ECO:0000269|PubMed:23506073"
FT HELIX 8..24
FT /evidence="ECO:0007829|PDB:4YZE"
FT TURN 26..28
FT /evidence="ECO:0007829|PDB:4YZE"
FT HELIX 31..38
FT /evidence="ECO:0007829|PDB:4YZE"
FT HELIX 42..48
FT /evidence="ECO:0007829|PDB:4YZE"
FT HELIX 52..77
FT /evidence="ECO:0007829|PDB:4YZE"
FT STRAND 78..80
FT /evidence="ECO:0007829|PDB:4YZE"
FT HELIX 82..95
FT /evidence="ECO:0007829|PDB:4YZE"
FT HELIX 107..112
FT /evidence="ECO:0007829|PDB:4YZE"
FT HELIX 113..117
FT /evidence="ECO:0007829|PDB:4YZE"
FT HELIX 120..146
FT /evidence="ECO:0007829|PDB:4YZE"
FT HELIX 156..177
FT /evidence="ECO:0007829|PDB:4YZE"
FT HELIX 181..193
FT /evidence="ECO:0007829|PDB:4YZE"
SQ SEQUENCE 199 AA; 22275 MW; E01FDD7D575A1E09 CRC64;
MNKHTEHDTR EHLLATGEQL CLQRGFTGMG LSELLKTAEV PKGSFYHYFR SKEAFGVAML
ERHYAAYHQR LTELLQSGEG NYRDRILAYY QQTLNQFCQH GTISGCLTVK LSAEVCDLSE
DMRSAMDKGA RGVIALLSQA LENGRENHCL TFCGEPLQQA QVLYALWLGA NLQAKISRSF
EPLENALAHV KNIIATPAV
