Escherichia coli K-12 substr. MG1655 Polypeptide: LeuC

Gene: leuC Accession Numbers: EG11576 (EcoCyc), b0072, ECK0074

Regulation Summary Diagram: ?

Regulation summary diagram for leuC

Component of: isopropylmalate isomerase

Isopropylmalate (IPM) isomerase catalyzes the second step in leucine biosynthesis, converting 2-isopropylmalate to 3-isopropylmalate. LeuC and LeuD are both required for the activity of IPM isomerase [Yang74].

The leucine operon consists of four structural genes (leuABCD) coding for the three enzymes which are specific for leucine biosynthesis. The gene for leuC and leuD code for the two subunits that make up the IPM isomerase. The gene for leuA codes for isopropylmalate synthase and leuB codes for isopropylmalate dehydrogenase. [Somers73] Based on the IPM isomerase in Salmonella typhimurium and cross-species complementation studies with that enzyme, E. coli IPM isomerase is likely to be a protein complex consisting of a 1:1 pairing of the gene product of leuC and leuD [Fultz81, Fultz79]. IPM isomerase heterodimer is an iron-sulfur cluster protein [Carlsen13].

Gene Citations: [Stratmann12]

Locations: cytosol

Map Position: [79,464 <- 80,864] (1.71 centisomes, 6°)
Length: 1401 bp / 466 aa

Molecular Weight of Polypeptide: 49.882 kD (from nucleotide sequence)

Unification Links: ASAP:ABE-0000261 , CGSC:570 , DIP:DIP-35834N , EchoBASE:EB1536 , EcoGene:EG11576 , EcoliWiki:b0072 , OU-Microarray:b0072 , PortEco:leuC , PR:PRO_000023083 , Pride:P0A6A6 , Protein Model Portal:P0A6A6 , RefSeq:NP_414614 , RegulonDB:EG11576 , SMR:P0A6A6 , String:511145.b0072 , UniProt:P0A6A6

Relationship Links: InterPro:IN-FAMILY:IPR001030 , InterPro:IN-FAMILY:IPR004430 , InterPro:IN-FAMILY:IPR015931 , InterPro:IN-FAMILY:IPR015932 , InterPro:IN-FAMILY:IPR015937 , InterPro:IN-FAMILY:IPR018136 , Panther:IN-FAMILY:PTHR11670 , Pfam:IN-FAMILY:PF00330 , Prints:IN-FAMILY:PR00415 , Prosite:IN-FAMILY:PS00450 , Prosite:IN-FAMILY:PS01244

In Paralogous Gene Group: 27 (4 members)

Gene-Reaction Schematic: ?

Gene-Reaction Schematic

Genetic Regulation Schematic: ?

Genetic regulation schematic for leuC

GO Terms:

Biological Process: GO:0009098 - leucine biosynthetic process Inferred from experiment Inferred by computational analysis [UniProtGOA12, UniProtGOA11a, GOA06, GOA01a, Yang74]
GO:0008152 - metabolic process Inferred by computational analysis [GOA01a]
GO:0008652 - cellular amino acid biosynthetic process Inferred by computational analysis [UniProtGOA11a]
GO:0009082 - branched-chain amino acid biosynthetic process Inferred by computational analysis [UniProtGOA11a]
Molecular Function: GO:0005515 - protein binding Inferred from experiment [Rajagopala14]
GO:0016836 - hydro-lyase activity Inferred from experiment [Yang74]
GO:0016866 - intramolecular transferase activity Inferred from experiment [Yang74]
GO:0003861 - 3-isopropylmalate dehydratase activity Inferred by computational analysis [GOA06, GOA01, GOA01a]
GO:0016829 - lyase activity Inferred by computational analysis [UniProtGOA11a]
GO:0046872 - metal ion binding Inferred by computational analysis [UniProtGOA11a]
GO:0051536 - iron-sulfur cluster binding Inferred by computational analysis [UniProtGOA11a]
GO:0051539 - 4 iron, 4 sulfur cluster binding Inferred by computational analysis [UniProtGOA11a, GOA01a]
Cellular Component: GO:0005829 - cytosol Inferred from experiment Inferred by computational analysis [DiazMejia09, Ishihama08, LopezCampistrou05]

MultiFun Terms: metabolism biosynthesis of building blocks amino acids leucine

Essentiality data for leuC 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 0.4% glucose No 37 Aerobic 7.2 0.27 No [Patrick07, Comment 3]
M9 medium with 1% glycerol No 37 Aerobic 7.2 0.35 No [Joyce06]
MOPS medium with 0.4% glucose Indeterminate 37 Aerobic 7.2 0.22 Yes [Baba06, Comment 2]
No [Feist07, Comment 4]

Revised 26-May-2011 by Brito D
Last-Curated ? 26-Sep-2013 by Kubo A , SRI International

Subunit of: isopropylmalate isomerase

Synonyms: 3-isopropylmalate dehydratase, α-isopropylmalate isomerase, α-IPM isomerase, IPMI, 3-isopropylmalate isomerase, 3-carboxy-3-hydroxy-isocaproate isomerase

Subunit composition of isopropylmalate isomerase = [LeuC][LeuD]

Last-Curated ? 13-Sep-2006 by Shearer A , SRI International

Enzymatic reaction of: (2R,3S)-3-isopropylmalate hydro-lyase (2-isopropylmaleate-forming) (isopropylmalate isomerase)

2-isopropylmaleate + H2O <=> (2R,3S)-3-isopropylmalate

The reaction direction shown, that is, A + B ↔ C + D versus C + D ↔ A + B, is in accordance with the direction in which it was curated.

The reaction is favored in the direction shown.

In Pathways: superpathway of branched amino acid biosynthesis , L-leucine biosynthesis

Enzymatic reaction of: (2S)-2-isopropylmalate hydro-lyase (2-isopropylmaleate-forming) (isopropylmalate isomerase)

(2S)-2-isopropylmalate <=> 2-isopropylmaleate + H2O

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 branched amino acid biosynthesis , L-leucine biosynthesis

Sequence Features

Protein sequence of LeuC with features indicated

Feature Class Location Citations Comment
Cleavage-of-Initial-Methionine 1
[Tonella98, Wilkins98, Link97, UniProt11]
UniProt: Removed.
Chain 2 -> 466
UniProt: 3-isopropylmalate dehydratase large subunit;
Sequence-Conflict 74
[Kirino94, UniProt10a]
UniProt: (in Ref. 5; BAA21004/BAA21005);
Metal-Binding-Site 347
UniProt: Iron-sulfur (4Fe-4S); Non-Experimental Qualifier: by similarity;
Metal-Binding-Site 407
UniProt: Iron-sulfur (4Fe-4S); Non-Experimental Qualifier: by similarity;
Metal-Binding-Site 410
UniProt: Iron-sulfur (4Fe-4S); Non-Experimental Qualifier: by similarity;

Gene Local Context (not to scale): ?

Gene local context diagram

Transcription Units:

Transcription-unit diagram

Transcription-unit diagram

Transcription-unit diagram


10/20/97 Gene b0072 from Blattner lab Genbank (v. M52) entry merged into EcoCyc gene EG11576; 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

Carlsen13: Carlsen S, Ajikumar PK, Formenti LR, Zhou K, Phon TH, Nielsen ML, Lantz AE, Kielland-Brandt MC, Stephanopoulos G (2013). "Heterologous expression and characterization of bacterial 2-C-methyl-D-erythritol-4-phosphate pathway in Saccharomyces cerevisiae." Appl Microbiol Biotechnol 97(13);5753-69. PMID: 23636690

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

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

Fultz79: Fultz PN, Kwoh DY, Kemper J (1979). "Salmonella typhimurium newD and Escherichia coli leuC genes code for a functional isopropylmalate isomerase in Salmonella typhimurium-Escherichia coli hybrids." J Bacteriol 137(3);1253-62. PMID: 374346

Fultz81: Fultz PN, Kemper J (1981). "Wild-type isopropylmalate isomerase in Salmonella typhimurium is composed of two different subunits." J Bacteriol 1981;148(1);210-9. PMID: 7026530

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

GOA01a: GOA, DDB, FB, MGI, ZFIN (2001). "Gene Ontology annotation through association of InterPro records with GO terms."

GOA06: GOA, SIB (2006). "Electronic Gene Ontology annotations created by transferring manual GO annotations between orthologous microbial proteins."

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

Kirino94: Kirino H, Aoki M, Aoshima M, Hayashi Y, Ohba M, Yamagishi A, Wakagi T, Oshima T (1994). "Hydrophobic interaction at the subunit interface contributes to the thermostability of 3-isopropylmalate dehydrogenase from an extreme thermophile, Thermus thermophilus." Eur J Biochem 220(1);275-81. PMID: 8119295

Link97: Link AJ, Robison K, Church GM (1997). "Comparing the predicted and observed properties of proteins encoded in the genome of Escherichia coli K-12." Electrophoresis 18(8);1259-313. PMID: 9298646

LopezCampistrou05: Lopez-Campistrous A, Semchuk P, Burke L, Palmer-Stone T, Brokx SJ, Broderick G, Bottorff D, Bolch S, Weiner JH, Ellison MJ (2005). "Localization, annotation, and comparison of the Escherichia coli K-12 proteome under two states of growth." Mol Cell Proteomics 4(8);1205-9. PMID: 15911532

Patrick07: Patrick WM, Quandt EM, Swartzlander DB, Matsumura I (2007). "Multicopy suppression underpins metabolic evolvability." Mol Biol Evol 24(12);2716-22. PMID: 17884825

Rajagopala14: Rajagopala SV, Sikorski P, Kumar A, Mosca R, Vlasblom J, Arnold R, Franca-Koh J, Pakala SB, Phanse S, Ceol A, Hauser R, Siszler G, Wuchty S, Emili A, Babu M, Aloy P, Pieper R, Uetz P (2014). "The binary protein-protein interaction landscape of Escherichia coli." Nat Biotechnol 32(3);285-90. PMID: 24561554

Somers73: Somers JM, Amzallag A, Middleton RB (1973). "Genetic fine structure of the leucine operon of Escherichia coli K-12." J Bacteriol 113(3);1268-72. PMID: 4570778

Stratmann12: Stratmann T, Pul Ü, Wurm R, Wagner R, Schnetz K (2012). "RcsB-BglJ activates the Escherichia coli leuO gene, encoding an H-NS antagonist and pleiotropic regulator of virulence determinants." Mol Microbiol 83(6);1109-23. PMID: 22295907

Tonella98: Tonella L, Walsh BJ, Sanchez JC, Ou K, Wilkins MR, Tyler M, Frutiger S, Gooley AA, Pescaru I, Appel RD, Yan JX, Bairoch A, Hoogland C, Morch FS, Hughes GJ, Williams KL, Hochstrasser DF (1998). "'98 Escherichia coli SWISS-2DPAGE database update." Electrophoresis 19(11);1960-71. PMID: 9740056

UniProt09: UniProt Consortium (2009). "UniProt version 15.8 released on 2009-10-01 00:00:00." Database.

UniProt10: UniProt Consortium (2010). "UniProt version 2010-07 released on 2010-06-15 00:00:00." Database.

UniProt10a: UniProt Consortium (2010). "UniProt version 2010-11 released on 2010-11-02 00:00:00." Database.

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

UniProtGOA11a: 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."

Wilkins98: Wilkins MR, Gasteiger E, Tonella L, Ou K, Tyler M, Sanchez JC, Gooley AA, Walsh BJ, Bairoch A, Appel RD, Williams KL, Hochstrasser DF (1998). "Protein identification with N and C-terminal sequence tags in proteome projects." J Mol Biol 278(3);599-608. PMID: 9600841

Yang74: Yang HL, Kessler DP (1974). "Genetic analysis of the leucine region in Escherichia coli B-r: gene-enzyme assignments." J Bacteriol 117(1);63-72. PMID: 4587614

Other References Related to Gene Regulation

Chen01a: Chen CC, Fang M, Majumder A, Wu HY (2001). "A 72-base pair AT-rich DNA sequence element functions as a bacterial gene silencer." J Biol Chem 276(12);9478-85. PMID: 11121424

Gemmill83: Gemmill RM, Jones JW, Haughn GW, Calvo JM (1983). "Transcription initiation sites of the leucine operons of Salmonella typhimurium and Escherichia coli." J Mol Biol 170(1);39-59. PMID: 6195343

Landgraf99: Landgraf JR, Boxer JA, Calvo JM (1999). "Escherichia coli Lrp (leucine-responsive regulatory protein) does not directly regulate expression of the leu operon promoter." J Bacteriol 181(20);6547-51. PMID: 10515950

Lin92: Lin R, D'Ari R, Newman EB (1992). "Lambda placMu insertions in genes of the leucine regulon: extension of the regulon to genes not regulated by leucine." J Bacteriol 1992;174(6);1948-55. PMID: 1532173

Vartak91: Vartak NB, Liu L, Wang BM, Berg CM (1991). "A functional leuABCD operon is required for leucine synthesis by the tyrosine-repressible transaminase in Escherichia coli K-12." J Bacteriol 173(12);3864-71. PMID: 1646790

Wessler81: Wessler SR, Calvo JM (1981). "Control of leu operon expression in Escherichia coli by a transcription attenuation mechanism." J Mol Biol 149(4);579-97. PMID: 6171647

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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 19.0 on Wed Oct 7, 2015, biocyc12.