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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

Manual assertion based on experiment ini

  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

    Pathwayi: glyoxylate 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)DescriptionActionsGraphical viewLength
    Metal bindingi157Magnesium1 Publication1
    Active sitei195Proton acceptor1 Publication1
    Binding sitei232Substrate1 Publication1
    Binding sitei351SubstrateBy similarity1

    GO - Molecular functioni

    • cation binding Source: EcoliWiki
    • isocitrate lyase activity Source: EcoliWiki
    • metal ion binding Source: UniProtKB-KW
    • transferase activity, transferring acyl groups, acyl groups converted into alkyl on transfer Source: GO_Central

    GO - Biological processi

    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 lineageiBacteriaProteobacteriaGammaproteobacteriaEnterobacteralesEnterobacteriaceaeEscherichia
    Proteomesi
    • UP000000318 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)DescriptionActionsGraphical viewLength
    Mutagenesisi195C → A: Large decrease in activity. 1 Publication1
    Mutagenesisi195C → S: Large decrease in activity. 1 Publication1
    Mutagenesisi219A → C: Isocitrate lyase activity is reduced compared to the wild-type. 1 Publication1

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Initiator methionineiRemoved1 Publication
    ChainiPRO_00000687742 – 434Isocitrate lyaseAdd BLAST433

    Keywords - PTMi

    Phosphoprotein

    Proteomic databases

    EPDiP0A9G6.
    PaxDbiP0A9G6.
    PRIDEiP0A9G6.

    2D gel databases

    SWISS-2DPAGEP0A9G6.

    Interactioni

    Subunit structurei

    Homotetramer.4 Publications

    Protein-protein interaction databases

    BioGridi4263469. 6 interactors.
    DIPiDIP-35893N.
    IntActiP0A9G6. 3 interactors.
    STRINGi511145.b4015.

    Structurei

    Secondary structure

    1434
    Legend: HelixTurnBeta strandPDB Structure known for this area
    Show more details
    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Helixi4 – 14Combined sources11
    Helixi18 – 20Combined sources3
    Helixi29 – 34Combined sources6
    Helixi44 – 57Combined sources14
    Turni58 – 60Combined sources3
    Beta strandi61 – 70Combined sources10
    Helixi74 – 83Combined sources10
    Beta strandi88 – 90Combined sources3
    Helixi92 – 98Combined sources7
    Beta strandi108 – 110Combined sources3
    Helixi116 – 137Combined sources22
    Beta strandi154 – 157Combined sources4
    Beta strandi162 – 164Combined sources3
    Helixi165 – 177Combined sources13
    Beta strandi181 – 188Combined sources8
    Helixi190 – 192Combined sources3
    Helixi206 – 223Combined sources18
    Beta strandi228 – 233Combined sources6
    Turni235 – 237Combined sources3
    Beta strandi240 – 242Combined sources3
    Helixi247 – 252Combined sources6
    Beta strandi253 – 257Combined sources5
    Beta strandi263 – 265Combined sources3
    Helixi269 – 279Combined sources11
    Helixi280 – 282Combined sources3
    Beta strandi284 – 288Combined sources5
    Helixi295 – 308Combined sources14
    Beta strandi313 – 317Combined sources5
    Helixi330 – 334Combined sources5
    Helixi336 – 343Combined sources8
    Beta strandi345 – 350Combined sources6
    Helixi353 – 371Combined sources19
    Helixi374 – 381Combined sources8
    Helixi383 – 390Combined sources8
    Turni391 – 393Combined sources3
    Helixi399 – 402Combined sources4
    Helixi405 – 415Combined sources11

    3D structure databases

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

    Miscellaneous databases

    EvolutionaryTraceiP0A9G6.

    Family & Domainsi

    Region

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Regioni91 – 93Substrate binding1 Publication3
    Regioni196 – 197Substrate bindingBy similarity2
    Regioni317 – 321Substrate bindingBy similarity5

    Sequence similaritiesi

    Phylogenomic databases

    eggNOGiENOG4108I9X. Bacteria.
    COG2224. LUCA.
    HOGENOMiHOG000238475.
    InParanoidiP0A9G6.
    KOiK01637.
    OMAiLEKDWAE.
    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]
    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)DescriptionActionsGraphical viewLength
    Sequence conflicti101 – 117LAASM…PANSV → WRPACIRISRSIRQTRC in CAA30416 (PubMed:3290857).CuratedAdd BLAST17
    Sequence conflicti215A → P in CAA30416 (PubMed:3290857).Curated1
    Sequence conflicti293P → R in AAA24009 (PubMed:2836370).Curated1
    Sequence conflicti338Q → E in CAA30416 (PubMed:3290857).Curated1
    Sequence conflicti419 – 434TSSVT…EESQF → DVFSHRADRLH (PubMed:3049537).CuratedAdd BLAST16

    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_LN832404.1.

    Genome annotation databases

    EnsemblBacteriaiAAC76985; AAC76985; b4015.
    BAE78017; BAE78017; BAE78017.
    GeneIDi948517.
    KEGGiecj:JW3975.
    eco: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_LN832404.1.

    3D structure databases

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

    Protein-protein interaction databases

    BioGridi4263469. 6 interactors.
    DIPiDIP-35893N.
    IntActiP0A9G6. 3 interactors.
    STRINGi511145.b4015.

    2D gel databases

    SWISS-2DPAGEP0A9G6.

    Proteomic databases

    EPDiP0A9G6.
    PaxDbiP0A9G6.
    PRIDEiP0A9G6.

    Protocols and materials databases

    Structural Biology KnowledgebaseSearch...

    Genome annotation databases

    EnsemblBacteriaiAAC76985; AAC76985; b4015.
    BAE78017; BAE78017; BAE78017.
    GeneIDi948517.
    KEGGiecj:JW3975.
    eco:b4015.
    PATRICi32123557. VBIEscCol129921_4127.

    Organism-specific databases

    EchoBASEiEB0021.
    EcoGeneiEG10022. aceA.

    Phylogenomic databases

    eggNOGiENOG4108I9X. Bacteria.
    COG2224. LUCA.
    HOGENOMiHOG000238475.
    InParanoidiP0A9G6.
    KOiK01637.
    OMAiLEKDWAE.
    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]
    PfamiPF00463. ICL. 2 hits.
    [Graphical view]
    SUPFAMiSSF51621. SSF51621. 1 hit.
    TIGRFAMsiTIGR01346. isocit_lyase. 2 hits.
    PROSITEiPS00161. ISOCITRATE_LYASE. 1 hit.
    [Graphical view]
    ProtoNetiSearch...

    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: November 2, 2016
    This is version 96 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

    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 one 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.