Escherichia coli K-12 substr. MG1655 Enzyme: isocitrate lyase

Gene: aceA Accession Numbers: EG10022 (EcoCyc), b4015, ECK4007

Synonyms: icl

Regulation Summary Diagram: ?

Regulation summary diagram for aceA

Subunit composition of isocitrate lyase = [AceA]4
         isocitrate lyase monomer = AceA

Citations: [Matsuoka88, Rieul88]

Gene Citations: [Maloy82, LaPorte85]

Locations: cytosol

Map Position: [4,215,132 -> 4,216,436] (90.85 centisomes, 327°)
Length: 1305 bp / 434 aa

Molecular Weight of Polypeptide: 47.522 kD (from nucleotide sequence)

Unification Links: ASAP:ABE-0013128 , CGSC:1052 , DIP:DIP-35893N , EchoBASE:EB0021 , EcoGene:EG10022 , EcoliWiki:b4015 , ModBase:P0A9G6 , OU-Microarray:b4015 , PortEco:aceA , PR:PRO_000022036 , Pride:P0A9G6 , Protein Model Portal:P0A9G6 , RefSeq:NP_418439 , RegulonDB:EG10022 , SMR:P0A9G6 , String:511145.b4015 , UniProt:P0A9G6

Relationship Links: InterPro:IN-FAMILY:IPR006254 , InterPro:IN-FAMILY:IPR015813 , InterPro:IN-FAMILY:IPR018523 , Panther:IN-FAMILY:PTHR21631:SF3 , PDB:Structure:1IGW , Pfam:IN-FAMILY:PF00463 , Prosite:IN-FAMILY:PS00161

Gene-Reaction Schematic: ?

Gene-Reaction Schematic

Genetic Regulation Schematic: ?

Genetic regulation schematic for aceA

GO Terms:

Biological Process: GO:0006097 - glyoxylate cycle Inferred by curator Inferred by computational analysis [UniProtGOA12, UniProtGOA11, Creaghan78]
GO:0006099 - tricarboxylic acid cycle Inferred by computational analysis [UniProtGOA11]
GO:0008152 - metabolic process Inferred by computational analysis [GOA01]
GO:0019752 - carboxylic acid metabolic process Inferred by computational analysis [GOA01]
Molecular Function: GO:0004451 - isocitrate lyase activity Inferred from experiment Inferred by computational analysis [GOA01a, GOA01, Hoyt88]
GO:0043169 - cation binding Inferred from experiment [Hoyt88]
GO:0003824 - catalytic activity Inferred by computational analysis [GOA01]
GO:0016829 - lyase activity Inferred by computational analysis [UniProtGOA11]
GO:0046872 - metal ion binding Inferred by computational analysis [UniProtGOA11]
Cellular Component: GO:0005829 - cytosol Inferred from experiment [Lasserre06]

MultiFun Terms: metabolism central intermediary metabolism glyoxylate bypass

Essentiality data for aceA 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]
Yes [Feist07, Comment 4]

Enzymatic reaction of: isocitrate lyase

EC Number:

D-threo-isocitrate <=> glyoxylate + succinate

The reaction direction shown, that is, A + B ↔ C + D versus C + D ↔ A + B, is in accordance with the direction of enzyme catalysis.

This reaction is reversible.

In Pathways: superpathway of glycolysis, pyruvate dehydrogenase, TCA, and glyoxylate bypass , superpathway of glyoxylate bypass and TCA , glyoxylate cycle

The second enzyme of the glyoxylate bypass. In one direction the reaction effects cleavage of isocitrate, in the other direction it effects condensation of glyoxylate and succinate. The enzyme is subject to phosphorylation[Hoyt88, Robertson88]. The enzyme is inactivated by reaction of iodoacetate with a cysteine residue at the active site [Nimmo89]. Values refer to cleavage direction of reaction

Citations: [Ko89]

Cofactors or Prosthetic Groups: Mg2+ [Comment 5]

Alternative Cofactors for Mg2+: Mn2+

Inhibitors (Competitive): phosphoenolpyruvate , 3-phospho-D-glycerate [Comment 6] , malonate [Comment 7] , oxalate [Comment 7]

Inhibitors (Uncompetitive): succinate [Hoyt88, Comment 8] , itaconate [Hoyt88, Comment 9]

Inhibitors (Unknown Mechanism): Hg2+ , 5,5'-dithio-bis-2-nitrobenzoate , 3-nitropropanoate [Helmward89, Hoyt88] , 2-hydroxymalonate [Hoyt88, Helmward89] , methylmalonate [Comment 10] , 2-oxoglutarate , phosphoenolpyruvate , Ca2+ , cis-aconitate , chloride , glycolate [Comment 10]

Kinetic Parameters:

Km (μM)
[MacKintosh88, BRENDA14]
[MacKintosh88, BRENDA14]

pH(opt): 6.9 [BRENDA14, Watanabe04]

Sequence Features

Protein sequence of isocitrate lyase monomer with features indicated

Feature Class Location Citations Comment
Sequence-Conflict 101 -> 117
[Rieul88, UniProt10]
UniProt: (in Ref. 3; CAA30416);
Mutagenesis-Variant 195
[Robertson95a, UniProt11]
C → A or S: Large decrease in activity.
Active-Site 195
UniProt: Non-Experimental Qualifier: probable;
Sequence-Conflict 215
[Rieul88, UniProt10]
UniProt: (in Ref. 3; CAA30416);
Sequence-Conflict 293
[Klumpp88, UniProt10]
UniProt: (in Ref. 8; AAA24009);
Sequence-Conflict 338
[Rieul88, UniProt10]
UniProt: (in Ref. 3; CAA30416);
Sequence-Conflict 419 -> 434
[Matsuoka88, UniProt10]
UniProt: (in Ref. 4);

Gene Local Context (not to scale): ?

Gene local context diagram

Transcription Units:

Transcription-unit diagram

Transcription-unit diagram


10/20/97 Gene b4015 from Blattner lab Genbank (v. M52) entry merged into EcoCyc gene EG10022; confirmed by SwissProt match.


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

BRENDA14: BRENDA team (2014). "Imported from BRENDA version existing on Aug 2014."

Creaghan78: Creaghan IT, Guest JR (1978). "Succinate dehydrogenase-dependent nutritional requirement for succinate in mutants of Escherichia coli K12." J Gen Microbiol 107(1);1-13. PMID: 366070

Feist07: Feist AM, Henry CS, Reed JL, Krummenacker M, Joyce AR, Karp PD, Broadbelt LJ, Hatzimanikatis V, Palsson BO (2007). "A genome-scale metabolic reconstruction for Escherichia coli K-12 MG1655 that accounts for 1260 ORFs and thermodynamic information." Mol Syst Biol 3;121. PMID: 17593909

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."

GOA01a: GOA, MGI (2001). "Gene Ontology annotation based on Enzyme Commission mapping." Genomics 74;121-128.

Helmward89: Helmward Z "Handbook of Enzyme Inhibitors. 2nd, revised and enlarged edition." Weinheim, Federal Republic of Germany ; New York, NY, USA , 1989.

Hoyt88: Hoyt JC, Robertson EF, Berlyn KA, Reeves HC (1988). "Escherichia coli isocitrate lyase: properties and comparisons." Biochim Biophys Acta 1988;966(1);30-5. PMID: 3291954

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

Klumpp88: Klumpp DJ, Plank DW, Bowdin LJ, Stueland CS, Chung T, LaPorte DC (1988). "Nucleotide sequence of aceK, the gene encoding isocitrate dehydrogenase kinase/phosphatase." J Bacteriol 170(6);2763-9. PMID: 2836370

Ko89: Ko YH, Vanni P, McFadden BA (1989). "The interaction of 3-phosphoglycerate and other substrate analogs with the glyoxylate- and succinate-binding sites of isocitrate lyase." Arch Biochem Biophys 1989;274(1);155-60. PMID: 2673042

LaPorte85: LaPorte DC, Thorsness PE, Koshland DE (1985). "Compensatory phosphorylation of isocitrate dehydrogenase. A mechanism for adaptation to the intracellular environment." J Biol Chem 260(19);10563-8. PMID: 3897222

Lasserre06: Lasserre JP, Beyne E, Pyndiah S, Lapaillerie D, Claverol S, Bonneu M (2006). "A complexomic study of Escherichia coli using two-dimensional blue native/SDS polyacrylamide gel electrophoresis." Electrophoresis 27(16);3306-21. PMID: 16858726

MacKintosh88: MacKintosh C, Nimmo HG (1988). "Purification and regulatory properties of isocitrate lyase from Escherichia coli ML308." Biochem J 1988;250(1);25-31. PMID: 3281659

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

Matsuoka88: Matsuoka M, McFadden BA (1988). "Isolation, hyperexpression, and sequencing of the aceA gene encoding isocitrate lyase in Escherichia coli." J Bacteriol 1988;170(10);4528-36. PMID: 3049537

Nimmo89: Nimmo HG, Douglas F, Kleanthous C, Campbell DG, MacKintosh C (1989). "Identification of a cysteine residue at the active site of Escherichia coli isocitrate lyase." Biochem J 1989;261(2);431-5. PMID: 2673221

Rieul88: Rieul C, Bleicher F, Duclos B, Cortay JC, Cozzone AJ (1988). "Nucleotide sequence of the aceA gene coding for isocitrate lyase in Escherichia coli." Nucleic Acids Res 1988;16(12);5689. PMID: 3290857

Robertson88: Robertson EF, Hoyt JC, Reeves HC (1988). "Evidence of histidine phosphorylation in isocitrate lyase from Escherichia coli." J Biol Chem 1988;263(5);2477-82. PMID: 3276689

Robertson95a: Robertson AG, Nimmo HG (1995). "Site-directed mutagenesis of cysteine-195 in isocitrate lyase from Escherichia coli ML308." Biochem J 305 ( Pt 1);239-44. PMID: 7826335

UniProt10: UniProt Consortium (2010). "UniProt version 2010-11 released on 2010-11-02 00:00:00." Database.

UniProt10a: UniProt Consortium (2010). "UniProt version 2010-07 released on 2010-06-15 00:00:00." Database.

UniProt11: UniProt Consortium (2011). "UniProt version 2011-06 released on 2011-06-30 00:00:00." Database.

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

UniProtGOA12: UniProt-GOA (2012). "Gene Ontology annotation based on UniPathway vocabulary mapping."

Watanabe04: Watanabe S, Takada Y (2004). "Amino acid residues involved in cold adaptation of isocitrate lyase from a psychrophilic bacterium, Colwellia maris." Microbiology 150(Pt 10);3393-403. PMID: 15470117

Other References Related to Gene Regulation

Chin89: Chin AM, Feldheim DA, Saier MH (1989). "Altered transcriptional patterns affecting several metabolic pathways in strains of Salmonella typhimurium which overexpress the fructose regulon." J Bacteriol 171(5);2424-34. PMID: 2496106

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

Cortay94: Cortay JC, Negre D, Scarabel M, Ramseier TM, Vartak NB, Reizer J, Saier MH, Cozzone AJ (1994). "In vitro asymmetric binding of the pleiotropic regulatory protein, FruR, to the ace operator controlling glyoxylate shunt enzyme synthesis." J Biol Chem 1994;269(21);14885-91. PMID: 8195118

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

Donald01a: Donald LJ, Hosfield DJ, Cuvelier SL, Ens W, Standing KG, Duckworth HW (2001). "Mass spectrometric study of the Escherichia coli repressor proteins, Ic1R and Gc1R, and their complexes with DNA." Protein Sci 10(7);1370-80. PMID: 11420439

Iuchi88: Iuchi S, Lin EC (1988). "arcA (dye), a global regulatory gene in Escherichia coli mediating repression of enzymes in aerobic pathways." Proc Natl Acad Sci U S A 1988;85(6);1888-92. PMID: 2964639

Kumar11: Kumar R, Shimizu K (2011). "Transcriptional regulation of main metabolic pathways of cyoA, cydB, fnr, and fur gene knockout Escherichia coli in C-limited and N-limited aerobic continuous cultures." Microb Cell Fact 10;3. PMID: 21272324

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

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

Ramseier93: Ramseier TM, Negre D, Cortay JC, Scarabel M, Cozzone AJ, Saier MH (1993). "In vitro binding of the pleiotropic transcriptional regulatory protein, FruR, to the fru, pps, ace, pts and icd operons of Escherichia coli and Salmonella typhimurium." J Mol Biol 234(1);28-44. PMID: 8230205

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

Son11: Son YJ, Phue JN, Trinh LB, Lee SJ, Shiloach J (2011). "The role of Cra in regulating acetate excretion and osmotic tolerance in E. coli K-12 and E. coli B at high density growth." Microb Cell Fact 10;52. PMID: 21718532

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

Zhang05: Zhang Z, Gosset G, Barabote R, Gonzalez CS, Cuevas WA, Saier MH (2005). "Functional interactions between the carbon and iron utilization regulators, Crp and Fur, in Escherichia coli." J Bacteriol 187(3);980-90. PMID: 15659676

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Please cite the following article in publications resulting from the use of EcoCyc: Nucleic Acids Research 41:D605-12 2013
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