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Escherichia coli K-12 substr. MG1655 Protein: IclR-glyox



Gene: iclR Accession Numbers: EG10491 (EcoCyc), b4018, ECK4010

Regulation Summary Diagram: ?

Subunit composition of IclR-glyox = [(IclR)(pyruvate)][glyoxylate]
         IclR-pyruvate DNA-binding transcriptional repressor = (IclR)(pyruvate) (extended summary available)
                 IclR transcriptional repressor = IclR (extended summary available)

Gene Citations: [Sunnarborg90]

Map Position: [4,220,827 <- 4,221,651] (90.97 centisomes)
Length: 825 bp / 274 aa

Unification Links: ASAP:ABE-0013136 , CGSC:614 , EchoBASE:EB0486 , EcoGene:EG10491 , OU-Microarray:b4018 , PortEco:iclR , RegulonDB:EG10491

In Reactions of unknown directionality:

Not in pathways:
IclR transcriptional repressor + glyoxylate = IclR-glyox

Gene-Reaction Schematic: ?

Genetic Regulation Schematic: ?

MultiFun Terms: information transfer RNA related Transcription related
metabolism central intermediary metabolism glyoxylate bypass
regulation genetic unit regulated operon
regulation type of regulation transcriptional level repressor


Subunit of IclR-glyox: IclR-pyruvate DNA-binding transcriptional repressor

Sequence Length: 274 AAs

GO Terms:

Biological Process: GO:0010629 - negative regulation of gene expression Inferred from experiment [Lorca07]
GO:0010944 - negative regulation of transcription by competitive promoter binding Inferred from experiment [Yamamoto03]
Molecular Function: GO:0001046 - core promoter sequence-specific DNA binding Inferred from experiment [Yamamoto03]

MultiFun Terms: information transfer RNA related Transcription related
metabolism central intermediary metabolism glyoxylate bypass
regulation genetic unit regulated operon
regulation type of regulation transcriptional level repressor

In Reactions of unknown directionality:

Not in pathways:
IclR + pyruvate = IclR transcriptional repressor
IclR transcriptional repressor + glyoxylate = IclR-glyox

Summary:
The transcription factor IclR, for "Isocitrate lyase Regulator," is negatively autoregulated [Gui96] and it regulates the expression of the glyoxylate bypass operon [Peskov08, Resnik96, Galinier91, Cortay89, Maloy82, Cortay91]. Transcription of this operon is induced when E. coli is grown during acetate accumulation in the exponential phase. Glyoxylate and pyruvate have been identified as effectors of IclR and show antagonistic effects. While glyoxylate favors the inactive dimeric state of IclR, pyruvate increases the binding of IclR to the aceBp promoter by stabilizing the active tetrameric form of the protein [Lorca07].

On other hand, the genes of the aceBAK operon are expressed to varied degrees due to two facts: first, they are differentially regulated at the translational level, and second, there is a putative premature transcriptional termination in the region preceding the aceK gene [Cozzone05].

IclR represses aceBAK transcription through two mechanisms [Yamamoto03]: (1) binding to the proximal site, overlapping the -35 promoter box, and preventing RNA polymerase binding [Pan96, Negre92, Cortay91], and (2) binding to the distal site after the RNA polymerase has bound to the promoter and formed the open complex, avoiding the polymerase escape of the promoter through its interaction with the α-subunits. Perhaps the IclR binding at both sites forms an intermolecular bridge that leads to a DNA loop structure and thus enhances the aceBAK repression [Yamamoto03].

This regulator belongs to the IclR family of repressors. IclR is composed of two domains: the amino-terminal domain, which contains the DNA-binding region, and the carboxy-terminal domain, which is responsible for inducer binding [Negre92, Sunnarborg90, Lorca07, Donald96, Negre91].

The crystal structure of the C-terminal domain of IclR (2.3Å) has been solved [Lorca07].

An iclR mutation affects the carbon flow in the metabolism [Lin05, Sanchez05].

Review: [zhouY12].


Subunit of IclR-pyruvate DNA-binding transcriptional repressor: IclR transcriptional repressor

Synonyms: IclR

Gene: iclR Accession Numbers: EG10491 (EcoCyc), b4018, ECK4010

Locations: cytosol

Sequence Length: 274 AAs

Molecular Weight: 29.739 kD (from nucleotide sequence)

pI: 8.59

GO Terms:

Biological Process: GO:0006355 - regulation of transcription, DNA-templated Inferred from experiment Inferred by computational analysis [UniProtGOA11, GOA01, Maloy82]
GO:0006097 - glyoxylate cycle Inferred by computational analysis [UniProtGOA11]
GO:0006351 - transcription, DNA-templated Inferred by computational analysis [UniProtGOA11]
Molecular Function: GO:0003677 - DNA binding Inferred by computational analysis [UniProtGOA11, GOA01]
Cellular Component: GO:0005829 - cytosol Inferred from experiment Inferred by computational analysis [DiazMejia09, Ishihama08]

MultiFun Terms: information transfer RNA related Transcription related
metabolism central intermediary metabolism glyoxylate bypass
regulation genetic unit regulated operon
regulation type of regulation transcriptional level repressor

Unification Links: DIP:DIP-10008N , EcoliWiki:b4018 , Mint:MINT-1226737 , ModBase:P16528 , PR:PRO_000022991 , Protein Model Portal:P16528 , RefSeq:NP_418442 , SMR:P16528 , String:511145.b4018 , UniProt:P16528

Relationship Links: InterPro:IN-FAMILY:IPR005471 , InterPro:IN-FAMILY:IPR011991 , InterPro:IN-FAMILY:IPR014757 , PDB:Structure:1TD5 , PDB:Structure:2O99 , PDB:Structure:2O9A , Pfam:IN-FAMILY:PF01614 , Pfam:IN-FAMILY:PF09339 , Prosite:IN-FAMILY:PS51077 , Prosite:IN-FAMILY:PS51078 , Smart:IN-FAMILY:SM00346

In Reactions of unknown directionality:

Not in pathways:
IclR + pyruvate = IclR transcriptional repressor
IclR + phosphoenolpyruvate = IclR-PEP

Summary:
The transcription factor IclR, for "Isocitrate lyase Regulator," is negatively autoregulated [Gui96] and it regulates the expression of the glyoxylate bypass operon [Peskov08, Resnik96, Galinier91, Cortay89, Maloy82, Cortay91]. Transcription of this operon is induced when E. coli is grown during acetate accumulation in the exponential phase. Glyoxylate and pyruvate have been identified as effectors of IclR and show antagonistic effects. While glyoxylate favors the inactive dimeric state of IclR, pyruvate increases the binding of IclR to the aceBp promoter by stabilizing the active tetrameric form of the protein [Lorca07].

On other hand, the genes of the aceBAK operon are expressed to varied degrees due to two facts: first, they are differentially regulated at the translational level, and second, there is a putative premature transcriptional termination in the region preceding the aceK gene [Cozzone05].

IclR represses aceBAK transcription through two mechanisms [Yamamoto03]: (1) binding to the proximal site, overlapping the -35 promoter box, and preventing RNA polymerase binding [Pan96, Negre92, Cortay91], and (2) binding to the distal site after the RNA polymerase has bound to the promoter and formed the open complex, avoiding the polymerase escape of the promoter through its interaction with the α-subunits. Perhaps the IclR binding at both sites forms an intermolecular bridge that leads to a DNA loop structure and thus enhances the aceBAK repression [Yamamoto03].

This regulator belongs to the IclR family of repressors. IclR is composed of two domains: the amino-terminal domain, which contains the DNA-binding region, and the carboxy-terminal domain, which is responsible for inducer binding [Negre92, Sunnarborg90, Lorca07, Donald96, Negre91].

The crystal structure of the C-terminal domain of IclR (2.3Å) has been solved [Lorca07].

An iclR mutation affects the carbon flow in the metabolism [Lin05, Sanchez05]. Under glucose-abundant conditions, a double mutant of IclR and ArcA causes an increase in biomass yield (47%) and reduction of acetate (70%) and CO2 (16%) production. Under glucose-limited conditions, this double mutant exhibits an increase of biomass of only 13% [Waegeman11].

Citations: [Blattner93]

Essentiality data for iclR knockouts: ?

Growth Medium Growth? T (°C) O2 pH Osm/L Growth Observations
LB enriched Yes 37 Aerobic 6.95   Yes [Gerdes03, Comment 1]
LB Lennox Yes 37 Aerobic 7   Yes [Baba06, Comment 2]
M9 medium with 1% glycerol Yes 37 Aerobic 7.2 0.35 Yes [Joyce06, Comment 3]
MOPS medium with 0.4% glucose Yes 37 Aerobic 7.2 0.22 Yes [Baba06, Comment 2]


Gene Local Context (not to scale): ?

Transcription Unit:

Notes:

History:
Martin Peralta on Fri Oct 29, 2004:
The start site of this gene was originally assigned solely on the basis of sequence considerations [Blattner97 ]. However, it was changed because Sunnarborg et al [Sunnarborg90 ] determined the nucleotide sequence of iclR from wich deduced its amino acid sequence. The demonstration is based on comparisons of the new gene sequence with homologous proteins, plus identification of both a plausible ribosome binding site and a promoter at an appropriate distance from the new start site.
10/20/97 Gene b4018 from Blattner lab Genbank (v. M52) entry merged into EcoCyc gene EG10491; confirmed by SwissProt match.


References

Baba06: Baba T, Ara T, Hasegawa M, Takai Y, Okumura Y, Baba M, Datsenko KA, Tomita M, Wanner BL, Mori H (2006). "Construction of Escherichia coli K-12 in-frame, single-gene knockout mutants: the Keio collection." Mol Syst Biol 2;2006.0008. PMID: 16738554

Blattner93: Blattner FR, Burland V, Plunkett G, Sofia HJ, Daniels DL (1993). "Analysis of the Escherichia coli genome. IV. DNA sequence of the region from 89.2 to 92.8 minutes." Nucleic Acids Res 1993;21(23);5408-17. PMID: 8265357

Blattner97: Blattner FR, Plunkett G, Bloch CA, Perna NT, Burland V, Riley M, Collado-Vides J, Glasner JD, Rode CK, Mayhew GF, Gregor J, Davis NW, Kirkpatrick HA, Goeden MA, Rose DJ, Mau B, Shao Y (1997). "The complete genome sequence of Escherichia coli K-12." Science 277(5331);1453-74. PMID: 9278503

Cortay89: Cortay JC, Bleicher F, Duclos B, Cenatiempo Y, Gautier C, Prato JL, Cozzone AJ (1989). "Utilization of acetate in Escherichia coli: structural organization and differential expression of the ace operon." Biochimie 71(9-10):1043-1049. PMID: 2512996

Cortay91: Cortay JC, Negre D, Galinier A, Duclos B, Perriere G, Cozzone AJ (1991). "Regulation of the acetate operon in Escherichia coli: purification and functional characterization of the IclR repressor." EMBO J 1991;10(3);675-9. PMID: 2001680

Cozzone05: Cozzone AJ, El-Mansi M (2005). "Control of isocitrate dehydrogenase catalytic activity by protein phosphorylation in Escherichia coli." J Mol Microbiol Biotechnol 9(3-4);132-46. PMID: 16415587

DiazMejia09: Diaz-Mejia JJ, Babu M, Emili A (2009). "Computational and experimental approaches to chart the Escherichia coli cell-envelope-associated proteome and interactome." FEMS Microbiol Rev 33(1);66-97. PMID: 19054114

Donald96: Donald LJ, Chernushevich IV, Zhou J, Verentchikov A, Poppe-Schriemer N, Hosfield DJ, Westmore JB, Ens W, Duckworth HW, Standing KG (1996). "Preparation and properties of pure, full-length IclR protein of Escherichia coli. Use of time-of-flight mass spectrometry to investigate the problems encountered." Protein Sci 5(8);1613-24. PMID: 8844850

Galinier91: Galinier A, Bleicher F, Negre D, Perriere G, Duclos B, Cozzone AJ, Cortay JC (1991). "Primary structure of the intergenic region between aceK and iclR in the Escherichia coli chromosome." Gene 1991;97(1);149-50. PMID: 1995429

Gerdes03: Gerdes SY, Scholle MD, Campbell JW, Balazsi G, Ravasz E, Daugherty MD, Somera AL, Kyrpides NC, Anderson I, Gelfand MS, Bhattacharya A, Kapatral V, D'Souza M, Baev MV, Grechkin Y, Mseeh F, Fonstein MY, Overbeek R, Barabasi AL, Oltvai ZN, Osterman AL (2003). "Experimental determination and system level analysis of essential genes in Escherichia coli MG1655." J Bacteriol 185(19);5673-84. PMID: 13129938

GOA01: GOA, DDB, FB, MGI, ZFIN (2001). "Gene Ontology annotation through association of InterPro records with GO terms."

Gui96: Gui L, Sunnarborg A, Pan B, LaPorte DC (1996). "Autoregulation of iclR, the gene encoding the repressor of the glyoxylate bypass operon." J Bacteriol 178(1);321-4. PMID: 8550439

Ishihama08: Ishihama Y, Schmidt T, Rappsilber J, Mann M, Hartl FU, Kerner MJ, Frishman D (2008). "Protein abundance profiling of the Escherichia coli cytosol." BMC Genomics 9;102. PMID: 18304323

Joyce06: Joyce AR, Reed JL, White A, Edwards R, Osterman A, Baba T, Mori H, Lesely SA, Palsson BO, Agarwalla S (2006). "Experimental and computational assessment of conditionally essential genes in Escherichia coli." J Bacteriol 188(23);8259-71. PMID: 17012394

Lin05: Lin H, Bennett GN, San KY (2005). "Genetic reconstruction of the aerobic central metabolism in Escherichia coli for the absolute aerobic production of succinate." Biotechnol Bioeng 89(2);148-56. PMID: 15543598

Lorca07: Lorca GL, Ezersky A, Lunin VV, Walker JR, Altamentova S, Evdokimova E, Vedadi M, Bochkarev A, Savchenko A (2007). "Glyoxylate and pyruvate are antagonistic effectors of the Escherichia coli IclR transcriptional regulator." J Biol Chem 282(22);16476-91. PMID: 17426033

Maloy82: Maloy SR, Nunn WD (1982). "Genetic regulation of the glyoxylate shunt in Escherichia coli K-12." J Bacteriol 1982;149(1);173-80. PMID: 7033207

Negre91: Negre D, Cortay JC, Old IG, Galinier A, Richaud C, Saint Girons I, Cozzone AJ (1991). "Overproduction and characterization of the iclR gene product of Escherichia coli K-12 and comparison with that of Salmonella typhimurium LT2." Gene 1991;97(1);29-37. PMID: 1995431

Negre92: Negre D, Cortay JC, Galinier A, Sauve P, Cozzone AJ (1992). "Specific interactions between the IclR repressor of the acetate operon of Escherichia coli and its operator." J Mol Biol 1992;228(1);23-9. PMID: 1447784

Pan96: Pan B, Unnikrishnan I, LaPorte DC (1996). "The binding site of the IclR repressor protein overlaps the promoter of aceBAK." J Bacteriol 178(13);3982-4. PMID: 8682810

Peskov08: Peskov K, Goryanin I, Prank K, Tobin F, Demin O (2008). "Kinetic modeling of ace operon genetic regulation in Escherichia coli." J Bioinform Comput Biol 6(5);933-59. PMID: 18942160

Resnik96: Resnik E, Pan B, Ramani N, Freundlich M, LaPorte DC (1996). "Integration host factor amplifies the induction of the aceBAK operon of Escherichia coli by relieving IclR repression." J Bacteriol 1996;178(9);2715-7. PMID: 8626344

Sanchez05: Sanchez AM, Bennett GN, San KY (2005). "Novel pathway engineering design of the anaerobic central metabolic pathway in Escherichia coli to increase succinate yield and productivity." Metab Eng 7(3);229-39. PMID: 15885621

Sunnarborg90: Sunnarborg A, Klumpp D, Chung T, LaPorte DC (1990). "Regulation of the glyoxylate bypass operon: cloning and characterization of iclR." J Bacteriol 1990;172(5);2642-9. PMID: 2185227

UniProtGOA11: UniProt-GOA (2011). "Gene Ontology annotation based on manual assignment of UniProtKB keywords in UniProtKB/Swiss-Prot entries."

Waegeman11: Waegeman H, Beauprez J, Moens H, Maertens J, De Mey M, Foulquie-Moreno MR, Heijnen JJ, Charlier D, Soetaert W (2011). "Effect of iclR and arcA knockouts on biomass formation and metabolic fluxes in Escherichia coli K12 and its implications on understanding the metabolism of Escherichia coli BL21 (DE3)." BMC Microbiol 11;70. PMID: 21481254

Yamamoto03: Yamamoto K, Ishihama A (2003). "Two different modes of transcription repression of the Escherichia coli acetate operon by IclR." Mol Microbiol 47(1);183-94. PMID: 12492863

zhouY12: zhou Y, Huang H, Zhou P, Xie J (2012). "Molecular mechanisms underlying the function diversity of transcriptional factor IclR family." Cell Signal 24(6);1270-5. PMID: 22382436

Other References Related to Gene Regulation

Gui96a: Gui L, Sunnarborg A, LaPorte DC (1996). "Regulated expression of a repressor protein: FadR activates iclR." J Bacteriol 1996;178(15);4704-9. PMID: 8755903


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Please cite the following article in publications resulting from the use of EcoCyc: Nucleic Acids Research 41:D605-12 2013
Page generated by SRI International Pathway Tools version 18.5 on Wed Dec 17, 2014, biocyc12.