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P0A9E5 (FNR_ECOLI) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 80. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (2) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Fumarate and nitrate reduction regulatory protein
Gene names
Name:fnr
Synonyms:nirR
Ordered Locus Names:b1334, JW1328
OrganismEscherichia coli (strain K12) [Reference proteome] [HAMAP]
Taxonomic identifier83333 [NCBI]
Taxonomic lineageBacteriaProteobacteriaGammaproteobacteriaEnterobacterialesEnterobacteriaceaeEscherichia

Protein attributes

Sequence length250 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Global transcription factor that controls the expression of over 100 target genes in response to anoxia. It facilitates the adaptation to anaerobic growth conditions by regulating the expression of gene products that are involved in anaerobic energy metabolism. When the terminal electron acceptor, O2, is no longer available, it represses the synthesis of enzymes involved in aerobic respiration and increases the synthesis of enzymes required for anaerobic respiration.

Cofactor

Binds 1 4Fe-4S cluster per subunit.

Subunit structure

Homodimer. Ref.15

Subcellular location

Cytoplasm Probable.

Domain

The amino acid residues contacting the FNR target site on the DNA (5'-TTGATNNNNATCAA-3') are located in the putative DNA-recognition helix (alphaF), which contains the FNR motif (EXXSR). Three surface-exposed loops forming activating region 1 (AR1) in the downstream subunit of the dimer contact the C-terminal domain of the alpha subunit (alphaCTD) of RNA polymerase for activation of class I promoters (the 161-121 loop is the major AR1 activating determinant). At class II promoters, the AR1 of the upstream subunit contacts alphaCTD, promoting open complex formation; activating region 3 (AR3) of the downstream subunit contacts region 4 of the sigma70 subunit of RNA polymerase, to effect direct activation. At promoters repressed by FNR, tandem FNR dimers might interact with each other at AR1 to restrict access to a promoter or jam the promoter by their dual interaction with RNA polymerase alphaCTD.

Miscellaneous

FNR senses the oxygen concentration directly via the disassembly and reassembly of the [4Fe-4S] clusters. Anaerobic, de novo acquisition of the iron-sulfur cluster converts monomeric, inactive apo-FNR into a dimeric form containing two [4Fe-4S] clusters. This, in turn, enhances the affinity of FNR for specific DNA targets and mediates transcription regulation by establishing direct FNR-RNA polymerase contacts. With the increase in intracellular oxygen concentration, the [4Fe-4S] cluster is oxidized, producing a [2Fe-2S] cluster, which decays to apo-FNR. Apo-FNR [4SH] can be reversibly oxidized to a disulfide form [2SH,S-S], suggesting that FNR may be able to sense oxidative stress as well as normoxia. This interconversion may be mediated by agents such as glutathione or thioredoxin.

Sequence similarities

Contains 1 cyclic nucleotide-binding domain.

Contains 1 HTH crp-type DNA-binding domain.

Mass spectrometry

Molecular mass is 26823±6 Da from positions 10 - 250. Determined by ESI. Ref.9

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 250250Fumarate and nitrate reduction regulatory protein
PRO_0000100161

Regions

Domain164 – 23774HTH crp-type
DNA binding197 – 21620H-T-H motif By similarity
Region20 – 2910Essential for the oxygen-regulated activity
Region47 – 504Activating region 2A Potential
Region60 – 612Activating region 3A Potential
Region71 – 755Activating region 1A Potential
Region811Activating region 3B Potential
Region85 – 873Activating region 3C Potential
Region1121Activating region 3D Potential
Region116 – 1216Activating region 1B Potential
Region123 – 1242Activating region 2B Potential
Region127 – 1282Activating region 2C Potential
Region140 – 15920Dimerization Potential
Region181 – 19111Activating region 1C Potential

Sites

Metal binding201Iron-sulfur (4Fe-4S) Potential
Metal binding231Iron-sulfur (4Fe-4S) Potential
Metal binding291Iron-sulfur (4Fe-4S) Potential
Metal binding1221Iron-sulfur (4Fe-4S) Potential

Experimental info

Mutagenesis161C → A: No effect. Ref.10 Ref.15
Mutagenesis201C → S: Loss of activity. Ref.10 Ref.15
Mutagenesis221D → G: Loss of regulation by O(2). Ref.11 Ref.15
Mutagenesis231C → G: Loss of activity. Ref.10 Ref.15
Mutagenesis281L → H: Loss of regulation by O(2). Ref.11 Ref.15
Mutagenesis291C → G: Loss of activity. Ref.10 Ref.15
Mutagenesis431D → G: Decrease in activity; no effect on DNA-binding. Ref.13 Ref.15
Mutagenesis641E → Q: No effect. Ref.10 Ref.15
Mutagenesis721R → H: Decrease in activity; no effect on DNA-binding. Ref.13 Ref.15
Mutagenesis731S → F: Decrease in activity; no effect on DNA-binding. Ref.13 Ref.14 Ref.15
Mutagenesis811I → T: Decrease in activity; no effect on DNA-binding. Ref.12 Ref.15
Mutagenesis821T → P: Decrease in activity; no effect on DNA-binding. Ref.12 Ref.15
Mutagenesis851G → A: Decrease in activity; no effect on DNA-binding. Trace activity; when associated with P-187. Ref.12 Ref.14 Ref.15
Mutagenesis861D → A: Decrease in activity; no effect on DNA-binding. Ref.12 Ref.15
Mutagenesis871E → K: Decrease in activity; no effect on DNA-binding. Ref.12 Ref.15
Mutagenesis881Q → E: Decrease in activity; no effect on DNA-binding. Ref.12 Ref.15
Mutagenesis931H → R: Loss of regulation by O(2). Ref.11 Ref.15
Mutagenesis961G → D: Loss of activity. Ref.10 Ref.15
Mutagenesis1181T → A or P: Decrease in activity; no effect on DNA-binding. Ref.13 Ref.14 Ref.15
Mutagenesis1201M → I, R, T or V: Decrease in activity; no effect on DNA-binding. Ref.13 Ref.15
Mutagenesis1221C → A or S: Loss of activity. Ref.10 Ref.15
Mutagenesis1401R → A: Decrease in activity. Ref.15
Mutagenesis1431M → A: Decrease in activity. Ref.15
Mutagenesis1441M → A: Decrease in activity due to faulty dimerization. Ref.15
Mutagenesis1451R → A: Decrease in activity. Ref.15
Mutagenesis1461L → A: Decrease in activity. Ref.15
Mutagenesis1471M → A: Decrease in activity due to faulty dimerization. Ref.15
Mutagenesis1501E → K: Loss of regulation by O(2). Ref.11 Ref.15
Mutagenesis1511I → A: Decrease in activity due to faulty dimerization. Ref.15
Mutagenesis1541D → A, G or V: Loss of regulation by O(2). Ref.6 Ref.11 Ref.15
Mutagenesis1581I → A: Decrease in activity due to faulty dimerization. Ref.15
Mutagenesis1811F → L: Decrease in activity; no effect on DNA-binding. Ref.13 Ref.15
Mutagenesis1861F → S: Decrease in activity; no effect on DNA-binding. Ref.13 Ref.15
Mutagenesis1871S → P: Decrease in activity; no effect on DNA-binding. Trace activity; when associated with A-85. Ref.13 Ref.14 Ref.15
Mutagenesis1911F → L: Decrease in activity; no effect on DNA-binding. Ref.13 Ref.15

Sequences

Sequence LengthMass (Da)Tools
P0A9E5 [UniParc].

Last modified July 19, 2005. Version 1.
Checksum: 33F7BFA2972FF703

FASTA25027,967
        10         20         30         40         50         60 
MIPEKRIIRR IQSGGCAIHC QDCSISQLCI PFTLNEHELD QLDNIIERKK PIQKGQTLFK 

        70         80         90        100        110        120 
AGDELKSLYA IRSGTIKSYT ITEQGDEQIT GFHLAGDLVG FDAIGSGHHP SFAQALETSM 

       130        140        150        160        170        180 
VCEIPFETLD DLSGKMPNLR QQMMRLMSGE IKGDQDMILL LSKKNAEERL AAFIYNLSRR 

       190        200        210        220        230        240 
FAQRGFSPRE FRLTMTRGDI GNYLGLTVET ISRLLGRFQK SGMLAVKGKY ITIENNDALA 

       250 
QLAGHTRNVA 

« Hide

References

« Hide 'large scale' references
[1]"Nucleotide sequence of the fnr gene and primary structure of the Enr protein of Escherichia coli."
Shaw D.J., Guest J.R.
Nucleic Acids Res. 10:6119-6130(1982) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[2]"A 570-kb DNA sequence of the Escherichia coli K-12 genome corresponding to the 28.0-40.1 min region on the linkage map."
Aiba H., Baba T., Fujita K., Hayashi K., Inada T., Isono K., Itoh T., Kasai H., Kashimoto K., Kimura S., Kitakawa M., Kitagawa M., Makino K., Miki T., Mizobuchi K., Mori H., Mori T., Motomura K. expand/collapse author list , Nakade S., Nakamura Y., Nashimoto H., Nishio Y., Oshima T., Saito N., Sampei G., Seki Y., Sivasundaram S., Tagami H., Takeda J., Takemoto K., Takeuchi Y., Wada C., Yamamoto Y., Horiuchi T.
DNA Res. 3:363-377(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
Strain: K12 / W3110 / ATCC 27325 / DSM 5911.
[3]"The complete genome sequence of Escherichia coli K-12."
Blattner F.R., Plunkett G. III, Bloch C.A., Perna N.T., Burland V., Riley M., Collado-Vides J., Glasner J.D., Rode C.K., Mayhew G.F., Gregor J., Davis N.W., Kirkpatrick H.A., Goeden M.A., Rose D.J., Mau B., Shao Y.
Science 277:1453-1462(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
Strain: K12 / MG1655 / ATCC 47076.
[4]"Highly accurate genome sequences of Escherichia coli K-12 strains MG1655 and W3110."
Hayashi K., Morooka N., Yamamoto Y., Fujita K., Isono K., Choi S., Ohtsubo E., Baba T., Wanner B.L., Mori H., Horiuchi T.
Mol. Syst. Biol. 2:E1-E5(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
Strain: K12 / W3110 / ATCC 27325 / DSM 5911.
[5]"Isolation of intact FNR protein (Mr 30,000) of Escherichia coli."
Trageser M., Spiro S., Duchene A., Kojro E., Fahrenholz F., Guest J.R., Unden G.
Mol. Microbiol. 4:21-27(1990) [PubMed] [Europe PMC] [Abstract]
Cited for: PROTEIN SEQUENCE OF 1-19, SEQUENCE REVISION TO 29.
[6]"The activity of the Escherichia coli transcription factor FNR is regulated by a change in oligomeric state."
Lazazzera B.A., Bates D.M., Kiley P.J.
Genes Dev. 7:1993-2005(1993) [PubMed] [Europe PMC] [Abstract]
Cited for: CHARACTERIZATION, MUTAGENESIS OF ASP-154.
Strain: K12 / MG1655 / ATCC 47076.
[7]"Iron-sulfur cluster disassembly in the FNR protein of Escherichia coli by O2: [4Fe-4S] to [2Fe-2S] conversion with loss of biological activity."
Khoroshilova N., Popescu C., Muenck E., Beinert H., Kiley P.J.
Proc. Natl. Acad. Sci. U.S.A. 94:6087-6092(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: CHARACTERIZATION.
Strain: B.
[8]"Anaerobic acquisition of [4FE 4S] clusters by the inactive FNR(C20S) variant and restoration of activity by second-site amino acid substitutions."
Ralph E.T., Scott C., Jordan P.A., Thomson A.J., Guest J.R., Green J.
Mol. Microbiol. 39:1199-1211(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: CHARACTERIZATION, MUTAGENESIS.
[9]"Properties of FNR proteins substituted at each of the five cysteine residues."
Green J., Sharrocks A.D., Green B., Geisow M., Guest J.R.
Mol. Microbiol. 8:61-68(1993) [PubMed] [Europe PMC] [Abstract]
Cited for: MASS SPECTROMETRY, CHARACTERIZATION OF MUTANTS.
[10]"In vivo and in vitro mutants of FNR the anaerobic transcriptional regulator of E. coli."
Sharrocks A.D., Green J., Guest J.R.
FEBS Lett. 270:119-122(1990) [PubMed] [Europe PMC] [Abstract]
Cited for: MUTAGENESIS OF CYS-16; CYS-20; CYS-23; CYS-29; GLU-64; GLY-96 AND CYS-122.
Strain: K12 / W3110 / ATCC 27325 / DSM 5911.
[11]"Fnr mutants that activate gene expression in the presence of oxygen."
Kiley P.J., Reznikoff W.S.
J. Bacteriol. 173:16-22(1991) [PubMed] [Europe PMC] [Abstract]
Cited for: MUTAGENESIS OF ASP-22; LEU-28; HIS-93; GLU-150 AND ASP-154.
Strain: K12 / MG1655 / ATCC 47076.
[12]"The role of two surface exposed loops in transcription activation by the Escherichia coli CRP and FNR proteins."
Williams R., Bell A., Sims G., Busby S.J.W.
Nucleic Acids Res. 19:6705-6712(1991) [PubMed] [Europe PMC] [Abstract]
Cited for: MUTAGENESIS OF ILE-81; THR-82; GLY-85; ASP-86; GLU-87 AND GLN-88.
[13]"Transcription activation at class I FNR-dependent promoters: identification of the activating surface of FNR and the corresponding contact site in the C-terminal domain of the RNA polymerase alpha subunit."
Williams S.M., Savery N.J., Busby S.J.W., Wing H.J.
Nucleic Acids Res. 25:4028-4034(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: MUTAGENESIS OF ASP-43; ARG-72; SER-73; GLY-74; THR-118; MET-120; PHE-181; PHE-186; SER-187 AND PHE-191.
[14]"FNR-dependent activation of the class II dmsA and narG promoters of Escherichia coli requires FNR-activating regions 1 and 3."
Lamberg K.E., Kiley P.J.
Mol. Microbiol. 38:817-827(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: MUTAGENESIS OF SER-73; GLY-85; THR-118 AND SER-187.
Strain: K12 / MG1655 / ATCC 47076.
[15]"Characterization of the dimerization domain in the FNR transcription factor."
Moore L.J., Kiley P.J.
J. Biol. Chem. 276:45744-45750(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: MUTAGENESIS OF ALL RESIDUES IN THE DIMERIZATION HELIX.
Strain: K12 / MG1655 / ATCC 47076.
[16]"FNR and its role in oxygen-regulated gene expression in Escherichia coli."
Spiro S., Guest J.R.
FEMS Microbiol. Rev. 6:399-428(1990) [PubMed] [Europe PMC] [Abstract]
Cited for: REVIEW.
[17]"Oxygen sensing by the global regulator, FNR: the role of the iron-sulfur cluster."
Kiley P.J., Beinert H.
FEMS Microbiol. Rev. 22:341-352(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: REVIEW.
[18]"Functional versatility in the CRP-FNR superfamily of transcription factors: FNR and FLP."
Green J., Scott C., Guest J.R.
Adv. Microb. Physiol. 44:1-34(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: REVIEW.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
J01608 Genomic DNA. Translation: AAA87981.1. Sequence problems.
U00096 Genomic DNA. Translation: AAC74416.1.
AP009048 Genomic DNA. Translation: BAA14927.1.
PIRRGECF. A64883.
RefSeqNP_415850.1. NC_000913.3.
YP_489604.1. NC_007779.1.

3D structure databases

ProteinModelPortalP0A9E5.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

DIPDIP-9669N.
IntActP0A9E5. 8 interactions.
MINTMINT-1237977.
STRING511145.b1334.

Proteomic databases

PaxDbP0A9E5.
PRIDEP0A9E5.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblBacteriaAAC74416; AAC74416; b1334.
BAA14927; BAA14927; BAA14927.
GeneID12932858.
945908.
KEGGecj:Y75_p1311.
eco:b1334.
PATRIC32117944. VBIEscCol129921_1392.

Organism-specific databases

EchoBASEEB0321.
EcoGeneEG10325. fnr.

Phylogenomic databases

eggNOGCOG0664.
HOGENOMHOG000186461.
KOK01420.
OMAFSANQFR.
OrthoDBEOG6RVFWF.
PhylomeDBP0A9E5.

Enzyme and pathway databases

BioCycEcoCyc:PD00197.
ECOL316407:JW1328-MONOMER.

Gene expression databases

GenevestigatorP0A9E5.

Family and domain databases

Gene3D1.10.10.10. 1 hit.
2.60.120.10. 1 hit.
InterProIPR018490. cNMP-bd-like.
IPR000595. cNMP-bd_dom.
IPR012318. HTH_CRP_2.
IPR014710. RmlC-like_jellyroll.
IPR001808. Tscrpt_reg_HTH_Crp.
IPR018335. Tscrpt_reg_HTH_Crp-type_CS.
IPR011991. WHTH_DNA-bd_dom.
[Graphical view]
PfamPF00027. cNMP_binding. 1 hit.
PF00325. Crp. 1 hit.
[Graphical view]
PRINTSPR00034. HTHCRP.
SMARTSM00100. cNMP. 1 hit.
SM00419. HTH_CRP. 1 hit.
[Graphical view]
SUPFAMSSF51206. SSF51206. 1 hit.
PROSITEPS50042. CNMP_BINDING_3. 1 hit.
PS00042. HTH_CRP_1. 1 hit.
PS51063. HTH_CRP_2. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

PROP0A9E5.

Entry information

Entry nameFNR_ECOLI
AccessionPrimary (citable) accession number: P0A9E5
Secondary accession number(s): P03019
Entry history
Integrated into UniProtKB/Swiss-Prot: July 21, 1986
Last sequence update: July 19, 2005
Last modified: July 9, 2014
This is version 80 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programProkaryotic Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

Escherichia coli

Escherichia coli (strain K12): entries and cross-references to EcoGene