FADR_ECOLI
ID FADR_ECOLI Reviewed; 239 AA.
AC P0A8V6; P09371; P76827;
DT 07-JUN-2005, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 2.
DT 03-AUG-2022, entry version 134.
DE RecName: Full=Fatty acid metabolism regulator protein {ECO:0000255|HAMAP-Rule:MF_00696};
GN Name=fadR {ECO:0000255|HAMAP-Rule:MF_00696}; Synonyms=oleR, thdB;
GN OrderedLocusNames=b1187, JW1176;
OS Escherichia coli (strain K12).
OC Bacteria; Proteobacteria; Gammaproteobacteria; Enterobacterales;
OC Enterobacteriaceae; Escherichia.
OX NCBI_TaxID=83333;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=K12;
RX PubMed=2843809; DOI=10.1093/nar/16.16.7995;
RA Dirusso C.C.;
RT "Nucleotide sequence of the fadR gene, a multifunctional regulator of fatty
RT acid metabolism in Escherichia coli.";
RL Nucleic Acids Res. 16:7995-8009(1988).
RN [2]
RP SEQUENCE REVISION TO 147.
RC STRAIN=K12;
RA Dirusso C.C.;
RL Submitted (SEP-1995) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=K12 / W3110 / ATCC 27325 / DSM 5911;
RX PubMed=8905232; DOI=10.1093/dnares/3.3.137;
RA Oshima T., Aiba H., Baba T., Fujita K., Hayashi K., Honjo A., Ikemoto K.,
RA Inada T., Itoh T., Kajihara M., Kanai K., Kashimoto K., Kimura S.,
RA Kitagawa M., Makino K., Masuda S., Miki T., Mizobuchi K., Mori H.,
RA Motomura K., Nakamura Y., Nashimoto H., Nishio Y., Saito N., Sampei G.,
RA Seki Y., Tagami H., Takemoto K., Wada C., Yamamoto Y., Yano M.,
RA Horiuchi T.;
RT "A 718-kb DNA sequence of the Escherichia coli K-12 genome corresponding to
RT the 12.7-28.0 min region on the linkage map.";
RL DNA Res. 3:137-155(1996).
RN [4]
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 [5]
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 [6]
RP PROTEIN SEQUENCE OF 2-11, FUNCTION, ACTIVITY REGULATION, AND DNA-BINDING.
RX PubMed=1569108; DOI=10.1016/s0021-9258(18)42497-0;
RA DiRusso C.C., Heimert T.L., Metzger A.K.;
RT "Characterization of FadR, a global transcriptional regulator of fatty acid
RT metabolism in Escherichia coli. Interaction with the fadB promoter is
RT prevented by long chain fatty acyl coenzyme A.";
RL J. Biol. Chem. 267:8685-8691(1992).
RN [7]
RP FUNCTION, AND DNA-BINDING.
RX PubMed=8446033; DOI=10.1111/j.1365-2958.1993.tb01122.x;
RA DiRusso C.C., Metzger A.K., Heimert T.L.;
RT "Regulation of transcription of genes required for fatty acid transport and
RT unsaturated fatty acid biosynthesis in Escherichia coli by FadR.";
RL Mol. Microbiol. 7:311-322(1993).
RN [8]
RP FUNCTION, ACTIVITY REGULATION VIA ACYL-COA-BINDING, INDUCTION, DOMAIN,
RP MUTAGENESIS OF TYR-215; GLY-216; GLU-218; SER-219; GLY-220; TRP-223;
RP GLN-227; LYS-228 AND ASN-229, AND DNA-BINDING.
RX PubMed=7836365; DOI=10.1074/jbc.270.3.1092;
RA Raman N., DiRusso C.C.;
RT "Analysis of acyl coenzyme A binding to the transcription factor FadR and
RT identification of amino acid residues in the carboxyl terminus required for
RT ligand binding.";
RL J. Biol. Chem. 270:1092-1097(1995).
RN [9]
RP FUNCTION, SUBUNIT, DOMAIN, AND MUTAGENESIS OF ALA-9; ARG-35; ARG-49;
RP HIS-65; GLY-66 AND LYS-67.
RX PubMed=9388199; DOI=10.1074/jbc.272.49.30645;
RA Raman N., Black P.N., Dirusso C.C.;
RT "Characterization of the fatty acid-responsive transcription factor FadR.
RT Biochemical and genetic analyses of the native conformation and functional
RT domains.";
RL J. Biol. Chem. 272:30645-30650(1997).
RN [10]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=11859088; DOI=10.1074/jbc.m201399200;
RA Zhang Y.-M., Marrakchi H., Rock C.O.;
RT "The FabR (YijC) transcription factor regulates unsaturated fatty acid
RT biosynthesis in Escherichia coli.";
RL J. Biol. Chem. 277:15558-15565(2002).
RN [11]
RP FUNCTION, AND ACTIVITY REGULATION.
RC STRAIN=K12;
RX PubMed=19854834; DOI=10.1074/jbc.m109.068239;
RA Zhu K., Zhang Y.M., Rock C.O.;
RT "Transcriptional regulation of membrane lipid homeostasis in Escherichia
RT coli.";
RL J. Biol. Chem. 284:34880-34888(2009).
RN [12]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RC STRAIN=K12;
RX PubMed=21276098; DOI=10.1111/j.1365-2958.2011.07564.x;
RA Feng Y., Cronan J.E.;
RT "Complex binding of the FabR repressor of bacterial unsaturated fatty acid
RT biosynthesis to its cognate promoters.";
RL Mol. Microbiol. 80:195-218(2011).
RN [13]
RP X-RAY CRYSTALLOGRAPHY (2.00 ANGSTROMS), AND SUBUNIT.
RX PubMed=11013219; DOI=10.1093/emboj/19.19.5167;
RA van Aalten D.M., DiRusso C.C., Knudsen J., Wierenga R.K.;
RT "Crystal structure of FadR, a fatty acid-responsive transcription factor
RT with a novel acyl coenzyme A-binding fold.";
RL EMBO J. 19:5167-5177(2000).
RN [14]
RP X-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS) IN COMPLEX WITH COENZYME A OR DNA,
RP SUBUNIT, AND DOMAIN.
RX PubMed=11296236; DOI=10.1093/emboj/20.8.2041;
RA van Aalten D.M., DiRusso C.C., Knudsen J.;
RT "The structural basis of acyl coenzyme A-dependent regulation of the
RT transcription factor FadR.";
RL EMBO J. 20:2041-2050(2001).
RN [15]
RP X-RAY CRYSTALLOGRAPHY (1.5 ANGSTROMS) OF APOPROTEIN OR IN COMPLEX WITH DNA,
RP AND SUBUNIT.
RX PubMed=11279025; DOI=10.1074/jbc.m100195200;
RA Xu Y., Heath R.J., Li Z., Rock C.O., White S.W.;
RT "The FadR.DNA complex. Transcriptional control of fatty acid metabolism in
RT Escherichia coli.";
RL J. Biol. Chem. 276:17373-17379(2001).
CC -!- FUNCTION: Multifunctional regulator of fatty acid metabolism
CC (PubMed:1569108, PubMed:8446033, PubMed:9388199, PubMed:11859088,
CC PubMed:19854834, PubMed:21276098). Represses transcription of at least
CC eight genes required for fatty acid transport and beta-oxidation
CC including fadA, fadB, fadD, fadL and fadE (PubMed:9388199). Activates
CC transcription of at least three genes required for unsaturated fatty
CC acid biosynthesis: fabA, fabB and iclR, the gene encoding the
CC transcriptional regulator of the aceBAK operon encoding the glyoxylate
CC shunt enzymes (PubMed:9388199). {ECO:0000269|PubMed:11859088,
CC ECO:0000269|PubMed:1569108, ECO:0000269|PubMed:19854834,
CC ECO:0000269|PubMed:21276098, ECO:0000269|PubMed:7836365,
CC ECO:0000269|PubMed:8446033, ECO:0000269|PubMed:9388199}.
CC -!- ACTIVITY REGULATION: Binding of FadR to DNA is specifically inhibited
CC by long chain acyl-CoA compounds, but not by long chain fatty acids
CC (PubMed:1569108). Long chain acyl-CoA binds directly to the protein
CC preventing it from binding DNA, which derepresses genes for beta-
CC oxidation and prevents activation of genes for unsaturated fatty acid
CC biosynthesis (PubMed:7836365, PubMed:19854834).
CC {ECO:0000269|PubMed:1569108, ECO:0000269|PubMed:19854834}.
CC -!- SUBUNIT: Homodimer (PubMed:9388199, PubMed:11013219, PubMed:11296236,
CC PubMed:11279025). Binding of acyl-CoA alters conformation of the dimer,
CC separating the DNA-binding regions and disrupting DNA-binding
CC (PubMed:11296236). {ECO:0000269|PubMed:11013219,
CC ECO:0000269|PubMed:11279025, ECO:0000269|PubMed:11296236,
CC ECO:0000269|PubMed:9388199}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000255|HAMAP-Rule:MF_00696}.
CC -!- INDUCTION: By growth in the presence of long chain fatty acids (C14-
CC C18) (PubMed:7836365). {ECO:0000269|PubMed:7836365}.
CC -!- DOMAIN: The N-terminus binds DNA, the C-terminus (residues 83-239) is
CC responsible for dimerization (PubMed:9388199). The C-terminal domain
CC binds acyl-CoA (PubMed:7836365, PubMed:11296236).
CC {ECO:0000269|PubMed:11296236, ECO:0000269|PubMed:7836365,
CC ECO:0000269|PubMed:9388199}.
CC -!- DISRUPTION PHENOTYPE: Decreased transcription of fabA, low to no change
CC in levels of fabB (PubMed:11859088, PubMed:21276098). Up-regulation of
CC genes involved in beta-oxidation (fatty acid degradation, at least
CC fadA, fadB, fadE, fadH, fadI and fadJ) (PubMed:11859088). Increased
CC levels of fatty acids; double fadR-fabR deletions have the same
CC phenotype, suggesting a functional fadR gene is required for fabR
CC function (PubMed:11859088). {ECO:0000269|PubMed:11859088,
CC ECO:0000269|PubMed:21276098}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; X08087; CAA30881.1; -; Genomic_DNA.
DR EMBL; U00096; AAC74271.1; -; Genomic_DNA.
DR EMBL; AP009048; BAA36042.1; -; Genomic_DNA.
DR PIR; H64864; H64864.
DR RefSeq; NP_415705.1; NC_000913.3.
DR RefSeq; WP_000234823.1; NZ_STEB01000023.1.
DR PDB; 1E2X; X-ray; 2.00 A; A=1-239.
DR PDB; 1H9G; X-ray; 2.10 A; A=1-239.
DR PDB; 1H9T; X-ray; 3.25 A; A/B=1-239.
DR PDB; 1HW1; X-ray; 1.50 A; A/B=1-239.
DR PDB; 1HW2; X-ray; 3.25 A; A/B=1-239.
DR PDBsum; 1E2X; -.
DR PDBsum; 1H9G; -.
DR PDBsum; 1H9T; -.
DR PDBsum; 1HW1; -.
DR PDBsum; 1HW2; -.
DR AlphaFoldDB; P0A8V6; -.
DR SMR; P0A8V6; -.
DR BioGRID; 4260102; 14.
DR DIP; DIP-9564N; -.
DR IntAct; P0A8V6; 2.
DR STRING; 511145.b1187; -.
DR DrugBank; DB08231; Myristic acid.
DR jPOST; P0A8V6; -.
DR PaxDb; P0A8V6; -.
DR PRIDE; P0A8V6; -.
DR EnsemblBacteria; AAC74271; AAC74271; b1187.
DR EnsemblBacteria; BAA36042; BAA36042; BAA36042.
DR GeneID; 66674993; -.
DR GeneID; 948652; -.
DR KEGG; ecj:JW1176; -.
DR KEGG; eco:b1187; -.
DR PATRIC; fig|1411691.4.peg.1100; -.
DR EchoBASE; EB0277; -.
DR eggNOG; COG2186; Bacteria.
DR HOGENOM; CLU_017584_9_4_6; -.
DR InParanoid; P0A8V6; -.
DR OMA; WETAGPN; -.
DR PhylomeDB; P0A8V6; -.
DR BioCyc; EcoCyc:PD01520; -.
DR EvolutionaryTrace; P0A8V6; -.
DR PRO; PR:P0A8V6; -.
DR Proteomes; UP000000318; Chromosome.
DR Proteomes; UP000000625; Chromosome.
DR GO; GO:0005829; C:cytosol; IDA:EcoCyc.
DR GO; GO:0003677; F:DNA binding; IEA:UniProtKB-KW.
DR GO; GO:0003700; F:DNA-binding transcription factor activity; IEA:UniProtKB-UniRule.
DR GO; GO:0000062; F:fatty-acyl-CoA binding; IEA:InterPro.
DR GO; GO:0006631; P:fatty acid metabolic process; IEA:UniProtKB-KW.
DR GO; GO:0045892; P:negative regulation of transcription, DNA-templated; IMP:EcoCyc.
DR GO; GO:0045723; P:positive regulation of fatty acid biosynthetic process; IMP:CACAO.
DR GO; GO:0019217; P:regulation of fatty acid metabolic process; IGI:CACAO.
DR CDD; cd07377; WHTH_GntR; 1.
DR Gene3D; 1.10.10.10; -; 1.
DR Gene3D; 1.20.120.530; -; 1.
DR HAMAP; MF_00696; HTH_FadR; 1.
DR InterPro; IPR014178; FA-response_TF_FadR.
DR InterPro; IPR028374; FadR_C.
DR InterPro; IPR008920; TF_FadR/GntR_C.
DR InterPro; IPR000524; Tscrpt_reg_HTH_GntR.
DR InterPro; IPR036388; WH-like_DNA-bd_sf.
DR InterPro; IPR036390; WH_DNA-bd_sf.
DR PANTHER; PTHR43537:SF10; PTHR43537:SF10; 1.
DR Pfam; PF07840; FadR_C; 1.
DR Pfam; PF00392; GntR; 1.
DR PRINTS; PR00035; HTHGNTR.
DR SMART; SM00345; HTH_GNTR; 1.
DR SUPFAM; SSF46785; SSF46785; 1.
DR SUPFAM; SSF48008; SSF48008; 1.
DR TIGRFAMs; TIGR02812; fadR_gamma; 1.
DR PROSITE; PS50949; HTH_GNTR; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Activator; Cytoplasm; Direct protein sequencing; DNA-binding;
KW Fatty acid metabolism; Lipid metabolism; Reference proteome; Repressor;
KW Transcription; Transcription regulation.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000269|PubMed:1569108"
FT CHAIN 2..239
FT /note="Fatty acid metabolism regulator protein"
FT /id="PRO_0000050626"
FT DOMAIN 6..74
FT /note="HTH gntR-type"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00696"
FT DNA_BIND 34..69
FT /note="H-T-H motif"
FT /evidence="ECO:0000269|PubMed:11279025,
FT ECO:0000269|PubMed:11296236"
FT REGION 215..230
FT /note="Binds acyl-CoA"
FT /evidence="ECO:0000305|PubMed:7836365"
FT BINDING 99
FT /ligand="CoA"
FT /ligand_id="ChEBI:CHEBI:57287"
FT /evidence="ECO:0000269|PubMed:11296236"
FT BINDING 103..107
FT /ligand="CoA"
FT /ligand_id="ChEBI:CHEBI:57287"
FT /evidence="ECO:0000269|PubMed:11296236"
FT BINDING 213
FT /ligand="CoA"
FT /ligand_id="ChEBI:CHEBI:57287"
FT /evidence="ECO:0000269|PubMed:11296236"
FT BINDING 219
FT /ligand="CoA"
FT /ligand_id="ChEBI:CHEBI:57287"
FT /evidence="ECO:0000269|PubMed:11296236"
FT MUTAGEN 9
FT /note="A->V: Dominant negative to wild-type, decreased DNA-
FT binding."
FT /evidence="ECO:0000269|PubMed:9388199"
FT MUTAGEN 35
FT /note="R->C: Dominant negative to wild-type, decreased DNA-
FT binding."
FT /evidence="ECO:0000269|PubMed:9388199"
FT MUTAGEN 49
FT /note="R->A: Dominant negative to wild-type."
FT /evidence="ECO:0000269|PubMed:9388199"
FT MUTAGEN 65
FT /note="H->Y: Dominant negative to wild-type, decreased DNA-
FT binding."
FT /evidence="ECO:0000269|PubMed:9388199"
FT MUTAGEN 66
FT /note="G->D: Dominant negative to wild-type, decreased DNA-
FT binding."
FT /evidence="ECO:0000269|PubMed:9388199"
FT MUTAGEN 67
FT /note="K->S: Dominant negative to wild-type, decreased DNA-
FT binding."
FT /evidence="ECO:0000269|PubMed:9388199"
FT MUTAGEN 215
FT /note="Y->A: Loss of FadR repression."
FT /evidence="ECO:0000269|PubMed:7836365"
FT MUTAGEN 216
FT /note="G->A: Super-repressor, non-inducible phenotype,
FT cells cannot use long chain fatty acids as carbon source."
FT /evidence="ECO:0000269|PubMed:7836365"
FT MUTAGEN 218
FT /note="E->A: Reduced ability to repress."
FT /evidence="ECO:0000269|PubMed:7836365"
FT MUTAGEN 219
FT /note="S->A: Reduced ability to repress."
FT /evidence="ECO:0000269|PubMed:7836365"
FT MUTAGEN 219
FT /note="S->N: Super-repressor, non-inducible phenotype,
FT cells cannot use long chain fatty acids as carbon source.
FT Protein has 10-fold decreased affinity for C18:1-CoA, can
FT still bind fabA DNA and alter transcription."
FT /evidence="ECO:0000269|PubMed:7836365"
FT MUTAGEN 220
FT /note="G->A: Loss of FadR repression."
FT /evidence="ECO:0000269|PubMed:7836365"
FT MUTAGEN 223
FT /note="W->A: Super-repressor, non-inducible phenotype,
FT cells cannot use long chain fatty acids as carbon source."
FT /evidence="ECO:0000269|PubMed:7836365"
FT MUTAGEN 227
FT /note="Q->A: Loss of FadR repression."
FT /evidence="ECO:0000269|PubMed:7836365"
FT MUTAGEN 228
FT /note="K->A: Reduced ability to repress."
FT /evidence="ECO:0000269|PubMed:7836365"
FT MUTAGEN 229
FT /note="N->A: Loss of FadR repression."
FT /evidence="ECO:0000269|PubMed:7836365"
FT HELIX 8..21
FT /evidence="ECO:0007829|PDB:1HW1"
FT HELIX 34..41
FT /evidence="ECO:0007829|PDB:1HW1"
FT HELIX 45..57
FT /evidence="ECO:0007829|PDB:1HW1"
FT STRAND 60..64
FT /evidence="ECO:0007829|PDB:1HW1"
FT STRAND 67..71
FT /evidence="ECO:0007829|PDB:1HW1"
FT HELIX 74..77
FT /evidence="ECO:0007829|PDB:1HW1"
FT HELIX 80..82
FT /evidence="ECO:0007829|PDB:1HW1"
FT HELIX 83..89
FT /evidence="ECO:0007829|PDB:1HW1"
FT HELIX 91..93
FT /evidence="ECO:0007829|PDB:1HW1"
FT HELIX 94..119
FT /evidence="ECO:0007829|PDB:1HW1"
FT HELIX 121..129
FT /evidence="ECO:0007829|PDB:1HW1"
FT TURN 130..133
FT /evidence="ECO:0007829|PDB:1HW1"
FT HELIX 138..155
FT /evidence="ECO:0007829|PDB:1HW1"
FT HELIX 159..179
FT /evidence="ECO:0007829|PDB:1HW1"
FT HELIX 183..202
FT /evidence="ECO:0007829|PDB:1HW1"
FT HELIX 206..227
FT /evidence="ECO:0007829|PDB:1HW1"
SQ SEQUENCE 239 AA; 26969 MW; 1FECA0DDAD5EB830 CRC64;
MVIKAQSPAG FAEEYIIESI WNNRFPPGTI LPAERELSEL IGVTRTTLRE VLQRLARDGW
LTIQHGKPTK VNNFWETSGL NILETLARLD HESVPQLIDN LLSVRTNIST IFIRTAFRQH
PDKAQEVLAT ANEVADHADA FAELDYNIFR GLAFASGNPI YGLILNGMKG LYTRIGRHYF
ANPEARSLAL GFYHKLSALC SEGAHDQVYE TVRRYGHESG EIWHRMQKNL PGDLAIQGR
