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Protein

Isocitrate lyase

Gene

aceA

Organism
Escherichia coli (strain K12)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Involved in the metabolic adaptation in response to environmental changes. Catalyzes the reversible formation of succinate and glyoxylate from isocitrate, a key step of the glyoxylate cycle, which operates as an anaplerotic route for replenishing the tricarboxylic acid cycle during growth on fatty acid substrates.5 Publications

Catalytic activityi

Isocitrate = succinate + glyoxylate.3 Publications

Cofactori

Mg2+1 PublicationNote: Divalent metal cations. Can also use Mn2+ ion.1 Publication

Enzyme regulationi

Activated by phosphorylation on histidine. Competitively inhibited by 3-phosphosglycerate, oxalate, malate, chloride, phosphate and sulfate ions, and uncompetitively inhibited by succinate and phosphoenolpyruvate (PEP).3 Publications

Kineticsi

Kcat is 28.5 sec(-1) for isocitrate lyase activity with threo-D-isocitrate as substrate (at pH 7.3).1 Publication

  1. KM=0.076 µM for threo-D-isocitrate (at pH 7.3)1 Publication
  2. KM=8 µM for threo-D-isocitrate (at pH 7.5 and 25 degrees Celsius)1 Publication
  3. KM=32 µM for isocitrate (at pH 6.8)1 Publication
  4. KM=63 µM for isocitrate (at pH 7.3)1 Publication
  5. KM=130 µM for glyoxylate (at pH 7.3)1 Publication
  6. KM=590 µM for succinate (at pH 7.3)1 Publication

    pH dependencei

    Optimum pH is 7.3.1 Publication

    Pathway:iglyoxylate cycle

    This protein is involved in step 1 of the subpathway that synthesizes (S)-malate from isocitrate.1 Publication
    Proteins known to be involved in the 2 steps of the subpathway in this organism are:
    1. Isocitrate lyase (aceA)
    2. Malate synthase G (glcB), Malate synthase A (aceB)
    This subpathway is part of the pathway glyoxylate cycle, which is itself part of Carbohydrate metabolism.
    View all proteins of this organism that are known to be involved in the subpathway that synthesizes (S)-malate from isocitrate, the pathway glyoxylate cycle and in Carbohydrate metabolism.

    Sites

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Metal bindingi157 – 1571Magnesium1 Publication
    Active sitei195 – 1951Proton acceptor1 Publication
    Binding sitei232 – 2321Substrate1 Publication
    Binding sitei351 – 3511SubstrateBy similarity

    GO - Molecular functioni

    • cation binding Source: EcoliWiki
    • isocitrate lyase activity Source: EcoliWiki
    • metal ion binding Source: UniProtKB-KW

    GO - Biological processi

    • glyoxylate cycle Source: EcoliWiki
    • tricarboxylic acid cycle Source: UniProtKB-KW
    Complete GO annotation...

    Keywords - Molecular functioni

    Lyase

    Keywords - Biological processi

    Glyoxylate bypass, Tricarboxylic acid cycle

    Keywords - Ligandi

    Magnesium, Manganese, Metal-binding

    Enzyme and pathway databases

    BioCyciEcoCyc:ISOCIT-LYASE-MONOMER.
    ECOL316407:JW3975-MONOMER.
    MetaCyc:ISOCIT-LYASE-MONOMER.
    BRENDAi4.1.3.1. 2026.
    UniPathwayiUPA00703; UER00719.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Isocitrate lyase1 Publication (EC:4.1.3.13 Publications)
    Short name:
    ICL1 Publication
    Alternative name(s):
    Isocitrase1 Publication
    Isocitratase1 Publication
    Gene namesi
    Name:aceA1 Publication
    Synonyms:icl
    Ordered Locus Names:b4015, JW3975
    OrganismiEscherichia coli (strain K12)
    Taxonomic identifieri83333 [NCBI]
    Taxonomic lineageiBacteriaProteobacteriaGammaproteobacteriaEnterobacterialesEnterobacteriaceaeEscherichia
    ProteomesiUP000000318 Componenti: Chromosome UP000000625 Componenti: Chromosome

    Organism-specific databases

    EcoGeneiEG10022. aceA.

    Subcellular locationi

    GO - Cellular componenti

    • cytosol Source: UniProtKB
    Complete GO annotation...

    Pathology & Biotechi

    Mutagenesis

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Mutagenesisi195 – 1951C → A: Large decrease in activity. 1 Publication
    Mutagenesisi195 – 1951C → S: Large decrease in activity. 1 Publication
    Mutagenesisi219 – 2191A → C: Isocitrate lyase activity is reduced compared to the wild-type. 1 Publication

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Initiator methioninei1 – 11Removed1 Publication
    Chaini2 – 434433Isocitrate lyasePRO_0000068774Add
    BLAST

    Keywords - PTMi

    Phosphoprotein

    Proteomic databases

    PaxDbiP0A9G6.
    PRIDEiP0A9G6.

    2D gel databases

    SWISS-2DPAGEP0A9G6.

    Interactioni

    Subunit structurei

    Homotetramer.4 Publications

    Protein-protein interaction databases

    DIPiDIP-35893N.
    IntActiP0A9G6. 3 interactions.
    STRINGi511145.b4015.

    Structurei

    Secondary structure

    1
    434
    Legend: HelixTurnBeta strand
    Show more details
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Helixi4 – 1411Combined sources
    Helixi18 – 203Combined sources
    Helixi29 – 346Combined sources
    Helixi44 – 5714Combined sources
    Turni58 – 603Combined sources
    Beta strandi61 – 7010Combined sources
    Helixi74 – 8310Combined sources
    Beta strandi88 – 903Combined sources
    Helixi92 – 987Combined sources
    Beta strandi108 – 1103Combined sources
    Helixi116 – 13722Combined sources
    Beta strandi154 – 1574Combined sources
    Beta strandi162 – 1643Combined sources
    Helixi165 – 17713Combined sources
    Beta strandi181 – 1888Combined sources
    Helixi190 – 1923Combined sources
    Helixi206 – 22318Combined sources
    Beta strandi228 – 2336Combined sources
    Turni235 – 2373Combined sources
    Beta strandi240 – 2423Combined sources
    Helixi247 – 2526Combined sources
    Beta strandi253 – 2575Combined sources
    Beta strandi263 – 2653Combined sources
    Helixi269 – 27911Combined sources
    Helixi280 – 2823Combined sources
    Beta strandi284 – 2885Combined sources
    Helixi295 – 30814Combined sources
    Beta strandi313 – 3175Combined sources
    Helixi330 – 3345Combined sources
    Helixi336 – 3438Combined sources
    Beta strandi345 – 3506Combined sources
    Helixi353 – 37119Combined sources
    Helixi374 – 3818Combined sources
    Helixi383 – 3908Combined sources
    Turni391 – 3933Combined sources
    Helixi399 – 4024Combined sources
    Helixi405 – 41511Combined sources

    3D structure databases

    Select the link destinations:
    PDBei
    RCSB PDBi
    PDBji
    Links Updated
    EntryMethodResolution (Å)ChainPositionsPDBsum
    1IGWX-ray2.10A/B/C/D1-434[»]
    ProteinModelPortaliP0A9G6.
    SMRiP0A9G6. Positions 2-417.
    ModBaseiSearch...
    MobiDBiSearch...

    Miscellaneous databases

    EvolutionaryTraceiP0A9G6.

    Family & Domainsi

    Region

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Regioni91 – 933Substrate binding1 Publication
    Regioni196 – 1972Substrate bindingBy similarity
    Regioni317 – 3215Substrate bindingBy similarity

    Sequence similaritiesi

    Phylogenomic databases

    eggNOGiCOG2224.
    HOGENOMiHOG000238475.
    InParanoidiP0A9G6.
    KOiK01637.
    OMAiLEKDWAE.
    OrthoDBiEOG689HMX.
    PhylomeDBiP0A9G6.

    Family and domain databases

    Gene3Di3.20.20.60. 1 hit.
    InterProiIPR006254. Isocitrate_lyase.
    IPR018523. Isocitrate_lyase_ph_CS.
    IPR015813. Pyrv/PenolPyrv_Kinase-like_dom.
    [Graphical view]
    PANTHERiPTHR21631:SF3. PTHR21631:SF3. 1 hit.
    PfamiPF00463. ICL. 2 hits.
    [Graphical view]
    SUPFAMiSSF51621. SSF51621. 1 hit.
    TIGRFAMsiTIGR01346. isocit_lyase. 2 hits.
    PROSITEiPS00161. ISOCITRATE_LYASE. 1 hit.
    [Graphical view]

    Sequencei

    Sequence statusi: Complete.

    Sequence processingi: The displayed sequence is further processed into a mature form.

    P0A9G6-1 [UniParc]FASTAAdd to basket

    « Hide

            10         20         30         40         50
    MKTRTQQIEE LQKEWTQPRW EGITRPYSAE DVVKLRGSVN PECTLAQLGA
    60 70 80 90 100
    AKMWRLLHGE SKKGYINSLG ALTGGQALQQ AKAGIEAVYL SGWQVAADAN
    110 120 130 140 150
    LAASMYPDQS LYPANSVPAV VERINNTFRR ADQIQWSAGI EPGDPRYVDY
    160 170 180 190 200
    FLPIVADAEA GFGGVLNAFE LMKAMIEAGA AAVHFEDQLA SVKKCGHMGG
    210 220 230 240 250
    KVLVPTQEAI QKLVAARLAA DVTGVPTLLV ARTDADAADL ITSDCDPYDS
    260 270 280 290 300
    EFITGERTSE GFFRTHAGIE QAISRGLAYA PYADLVWCET STPDLELARR
    310 320 330 340 350
    FAQAIHAKYP GKLLAYNCSP SFNWQKNLDD KTIASFQQQL SDMGYKFQFI
    360 370 380 390 400
    TLAGIHSMWF NMFDLANAYA QGEGMKHYVE KVQQPEFAAA KDGYTFVSHQ
    410 420 430
    QEVGTGYFDK VTTIIQGGTS SVTALTGSTE ESQF
    Length:434
    Mass (Da):47,522
    Last modified:July 19, 2005 - v1
    Checksum:iF66449CCD1E168E9
    GO

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti101 – 11717LAASM…PANSV → WRPACIRISRSIRQTRC in CAA30416 (PubMed:3290857).CuratedAdd
    BLAST
    Sequence conflicti215 – 2151A → P in CAA30416 (PubMed:3290857).Curated
    Sequence conflicti293 – 2931P → R in AAA24009 (PubMed:2836370).Curated
    Sequence conflicti338 – 3381Q → E in CAA30416 (PubMed:3290857).Curated
    Sequence conflicti419 – 43416TSSVT…EESQF → DVFSHRADRLH (PubMed:3049537).CuratedAdd
    BLAST

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    X12431 Genomic DNA. Translation: CAA30974.1.
    X07543 Genomic DNA. Translation: CAA30416.1.
    M22621 Genomic DNA. Translation: AAC13650.1.
    U00006 Genomic DNA. Translation: AAC43109.1.
    U00096 Genomic DNA. Translation: AAC76985.1.
    AP009048 Genomic DNA. Translation: BAE78017.1.
    M20714 Genomic DNA. Translation: AAA24009.1.
    PIRiS05692. WZECIC.
    RefSeqiNP_418439.1. NC_000913.3.
    WP_000857856.1. NZ_CP010445.1.

    Genome annotation databases

    EnsemblBacteriaiAAC76985; AAC76985; b4015.
    BAE78017; BAE78017; BAE78017.
    GeneIDi948517.
    KEGGieco:b4015.
    PATRICi32123557. VBIEscCol129921_4127.

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    X12431 Genomic DNA. Translation: CAA30974.1.
    X07543 Genomic DNA. Translation: CAA30416.1.
    M22621 Genomic DNA. Translation: AAC13650.1.
    U00006 Genomic DNA. Translation: AAC43109.1.
    U00096 Genomic DNA. Translation: AAC76985.1.
    AP009048 Genomic DNA. Translation: BAE78017.1.
    M20714 Genomic DNA. Translation: AAA24009.1.
    PIRiS05692. WZECIC.
    RefSeqiNP_418439.1. NC_000913.3.
    WP_000857856.1. NZ_CP010445.1.

    3D structure databases

    Select the link destinations:
    PDBei
    RCSB PDBi
    PDBji
    Links Updated
    EntryMethodResolution (Å)ChainPositionsPDBsum
    1IGWX-ray2.10A/B/C/D1-434[»]
    ProteinModelPortaliP0A9G6.
    SMRiP0A9G6. Positions 2-417.
    ModBaseiSearch...
    MobiDBiSearch...

    Protein-protein interaction databases

    DIPiDIP-35893N.
    IntActiP0A9G6. 3 interactions.
    STRINGi511145.b4015.

    2D gel databases

    SWISS-2DPAGEP0A9G6.

    Proteomic databases

    PaxDbiP0A9G6.
    PRIDEiP0A9G6.

    Protocols and materials databases

    Structural Biology KnowledgebaseSearch...

    Genome annotation databases

    EnsemblBacteriaiAAC76985; AAC76985; b4015.
    BAE78017; BAE78017; BAE78017.
    GeneIDi948517.
    KEGGieco:b4015.
    PATRICi32123557. VBIEscCol129921_4127.

    Organism-specific databases

    EchoBASEiEB0021.
    EcoGeneiEG10022. aceA.

    Phylogenomic databases

    eggNOGiCOG2224.
    HOGENOMiHOG000238475.
    InParanoidiP0A9G6.
    KOiK01637.
    OMAiLEKDWAE.
    OrthoDBiEOG689HMX.
    PhylomeDBiP0A9G6.

    Enzyme and pathway databases

    UniPathwayiUPA00703; UER00719.
    BioCyciEcoCyc:ISOCIT-LYASE-MONOMER.
    ECOL316407:JW3975-MONOMER.
    MetaCyc:ISOCIT-LYASE-MONOMER.
    BRENDAi4.1.3.1. 2026.

    Miscellaneous databases

    EvolutionaryTraceiP0A9G6.
    PROiP0A9G6.

    Family and domain databases

    Gene3Di3.20.20.60. 1 hit.
    InterProiIPR006254. Isocitrate_lyase.
    IPR018523. Isocitrate_lyase_ph_CS.
    IPR015813. Pyrv/PenolPyrv_Kinase-like_dom.
    [Graphical view]
    PANTHERiPTHR21631:SF3. PTHR21631:SF3. 1 hit.
    PfamiPF00463. ICL. 2 hits.
    [Graphical view]
    SUPFAMiSSF51621. SSF51621. 1 hit.
    TIGRFAMsiTIGR01346. isocit_lyase. 2 hits.
    PROSITEiPS00161. ISOCITRATE_LYASE. 1 hit.
    [Graphical view]
    ProtoNetiSearch...

    Publicationsi

    « Hide 'large scale' publications
    1. "Nucleotide sequence of the aceB gene encoding malate synthase A in Escherichia coli."
      Byrne C.R., Stokes H.W., Ward K.A.
      Nucleic Acids Res. 16:9342-9342(1988) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
      Strain: K12.
    2. "Nucleotide sequence of the aceB gene encoding malate synthase A in Escherichia coli."
      Byrne C.R., Stokes H.W., Ward K.A.
      Nucleic Acids Res. 16:10924-10924(1988) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
      Strain: K12.
    3. "Nucleotide sequence of the aceA gene coding for isocitrate lyase in Escherichia coli."
      Rieul C., Bleicher F., Duclos B., Cortay J.-C., Cozzone A.J.
      Nucleic Acids Res. 16:5689-5689(1988) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
      Strain: K12.
    4. "Isolation, hyperexpression, and sequencing of the aceA gene encoding isocitrate lyase in Escherichia coli."
      Matsuoka M., McFadden B.A.
      J. Bacteriol. 170:4528-4536(1988) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], PROTEIN SEQUENCE OF 2-17, SUBUNIT.
    5. "Analysis of the Escherichia coli genome. IV. DNA sequence of the region from 89.2 to 92.8 minutes."
      Blattner F.R., Burland V.D., Plunkett G. III, Sofia H.J., Daniels D.L.
      Nucleic Acids Res. 21:5408-5417(1993) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
      Strain: K12 / MG1655 / ATCC 47076.
    6. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
      Strain: K12 / MG1655 / ATCC 47076.
    7. "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.
    8. "Nucleotide sequence of aceK, the gene encoding isocitrate dehydrogenase kinase/phosphatase."
      Klumpp D.J., Plank D.W., Bowdin L.J., Stueland C.S., Chung T., Laporte D.C.
      J. Bacteriol. 170:2763-2769(1988) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 293-434.
    9. "Purification and characterization of isocitrate lyase from Escherichia coli."
      Robertson E.F., Reeves H.C.
      Curr. Microbiol. 14:347-359(1986)
      Cited for: FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, SUBUNIT.
    10. "Purification and regulatory properties of isocitrate lyase from Escherichia coli ML308."
      MacKintosh C., Nimmo H.G.
      Biochem. J. 250:25-31(1988) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, ENZYME REGULATION, SUBUNIT.
      Strain: ML308.
    11. "Evidence of histidine phosphorylation in isocitrate lyase from Escherichia coli."
      Robertson E.F., Hoyt J.C., Reeves H.C.
      J. Biol. Chem. 263:2477-2482(1988) [PubMed] [Europe PMC] [Abstract]
      Cited for: PHOSPHORYLATION, ENZYME REGULATION.
    12. "Escherichia coli isocitrate lyase: properties and comparisons."
      Hoyt J.C., Robertson E.F., Berlyn K.A., Reeves H.C.
      Biochim. Biophys. Acta 966:30-35(1988) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, ENZYME REGULATION, COFACTOR.
    13. "Site-directed mutagenesis of cysteine-195 in isocitrate lyase from Escherichia coli ML308."
      Robertson A.G., Nimmo H.G.
      Biochem. J. 305:239-244(1995) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, MUTAGENESIS OF CYS-195, ACTIVE SITE.
      Strain: ML308.
    14. "The role of isocitrate lyase and the glyoxylate cycle in Escherichia coli growing under glucose limitation."
      Prasad Maharjan R., Yu P.L., Seeto S., Ferenci T.
      Res. Microbiol. 156:178-183(2005) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, PATHWAY.
    15. Cited for: X-RAY CRYSTALLOGRAPHY (2.10 ANGSTROMS) OF MUTANT CYS-219 IN COMPLEX WITH MAGNESIUM AND SUBSTRATE, MUTAGENESIS OF ALA-219, SUBUNIT.

    Entry informationi

    Entry nameiACEA_ECOLI
    AccessioniPrimary (citable) accession number: P0A9G6
    Secondary accession number(s): P05313, Q2M6T9
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: July 19, 2005
    Last sequence update: July 19, 2005
    Last modified: July 22, 2015
    This is version 90 of the entry and version 1 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programProkaryotic Protein Annotation Program

    Miscellaneousi

    Keywords - Technical termi

    3D-structure, Complete proteome, Direct protein sequencing, Reference proteome

    Documents

    1. Escherichia coli
      Escherichia coli (strain K12): entries and cross-references to EcoGene
    2. PATHWAY comments
      Index of metabolic and biosynthesis pathways
    3. PDB cross-references
      Index of Protein Data Bank (PDB) cross-references
    4. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3

    Similar proteinsi

    Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
    100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into Uniref entry.
    90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
    50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.