Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Protein

Isocitrate lyase

Gene

ICL1

Organism
Saccharomyces cerevisiae (strain ATCC 204508 / S288c) (Baker's yeast)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Catalyzes the 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. Required for growth on ethanol or acetate, but dispensable when fermentable carbon sources are available. Acts also on 2-methylisocitrate.6 Publications

Catalytic activityi

Isocitrate = succinate + glyoxylate.4 Publications
(2S,3R)-3-hydroxybutane-1,2,3-tricarboxylate = pyruvate + succinate.2 Publications

Cofactori

Mg2+By similarity

Enzyme regulationi

Phosphorylated and inactivated after addition of glucose to the cell culture (repressing conditions).1 Publication

Kineticsi

The Vmax with threo-D(S)-isocitrate as substrate is 5-fold higher than with threo-D(S)-2-methylisocitrate as substrate.2 Publications

  1. KM=1.4 mM for threo-D(S)-isocitrate (at pH 7.0)2 Publications
  2. KM=0.6 mM for threo-D(S)-2-methylisocitrate (at pH 7.0 and 30 degrees Celsius)2 Publications

    pH dependencei

    Optimum pH is 7.2 Publications

    Temperature dependencei

    Thermostable for 60 minutes up to 50 degrees Celsius.2 Publications

    Pathwayi

    Sites

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Metal bindingi179 – 1791MagnesiumBy similarity
    Active sitei217 – 2171Proton acceptorCurated
    Binding sitei254 – 2541SubstrateBy similarity
    Binding sitei471 – 4711SubstrateBy similarity

    GO - Molecular functioni

    • isocitrate lyase activity Source: SGD
    • metal ion binding Source: UniProtKB-KW
    • methylisocitrate lyase activity Source: UniProtKB-EC

    GO - Biological processi

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

    Keywords - Molecular functioni

    Lyase

    Keywords - Biological processi

    Glyoxylate bypass, Tricarboxylic acid cycle

    Keywords - Ligandi

    Magnesium, Metal-binding

    Enzyme and pathway databases

    BioCyciYEAST:YER065C-MONOMER.
    SABIO-RKP28240.
    UniPathwayiUPA00703; UER00719.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Isocitrate lyase1 Publication (EC:4.1.3.14 Publications)
    Short name:
    ICLCurated
    Alternative name(s):
    Methylisocitrate lyase1 Publication (EC:4.1.3.302 Publications)
    Short name:
    MICACurated
    Threo-D(S)-isocitrate glyoxylate-lyaseCurated
    Gene namesi
    Name:ICL11 Publication
    Ordered Locus Names:YER065CImported
    OrganismiSaccharomyces cerevisiae (strain ATCC 204508 / S288c) (Baker's yeast)
    Taxonomic identifieri559292 [NCBI]
    Taxonomic lineageiEukaryotaFungiDikaryaAscomycotaSaccharomycotinaSaccharomycetesSaccharomycetalesSaccharomycetaceaeSaccharomyces
    ProteomesiUP000002311 Componenti: Chromosome V

    Organism-specific databases

    CYGDiYER065c.
    EuPathDBiFungiDB:YER065C.
    SGDiS000000867. ICL1.

    Subcellular locationi

    GO - Cellular componenti

    • cytoplasm Source: SGD
    • proteinaceous extracellular matrix Source: UniProtKB-SubCell
    • vacuole Source: UniProtKB-SubCell
    Complete GO annotation...

    Keywords - Cellular componenti

    Cytoplasm, Extracellular matrix, Secreted, Vacuole

    Pathology & Biotechi

    Disruption phenotypei

    Impairs growth when acetate or ethanol are the sole carbon source. Leads to reduced chronological lifespan.5 Publications

    Mutagenesis

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Mutagenesisi53 – 531T → A: Abolishes short-term enzyme inactivation by glucose addition. 1 Publication
    Mutagenesisi216 – 2161K → R: Reduces activity by 45%; when associated with L-220. 1 Publication
    Mutagenesisi220 – 2201M → L: Reduces activity by 45%; when associated with R-216. 1 Publication

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 557557Isocitrate lyasePRO_0000068799Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Modified residuei53 – 531PhosphothreonineSequence Analysis

    Post-translational modificationi

    Phosphorylated in response to elevated glucose levels, leading first to reversible inactivation of the enzyme (short-term inactivation), and at a later stage to proteolytic degradation of the protein (long-term inactivation).1 Publication

    Keywords - PTMi

    Phosphoprotein

    Proteomic databases

    MaxQBiP28240.
    PaxDbiP28240.
    PeptideAtlasiP28240.

    Expressioni

    Inductioni

    Repressed by glucose and induced by ethanol via the transcriptional activator CAT8. The promoter sequence located between -397 and -388 contains an upstream activating sequence (UAS)element whereas the sequence located between -261 and -242 contains an upstream repressing sequence (URS) element.5 Publications

    Gene expression databases

    GenevestigatoriP28240.

    Interactioni

    Subunit structurei

    Homotetramer.1 Publication

    Protein-protein interaction databases

    BioGridi36807. 31 interactions.
    DIPiDIP-1663N.
    IntActiP28240. 2 interactions.
    MINTiMINT-400647.
    STRINGi4932.YER065C.

    Structurei

    3D structure databases

    ProteinModelPortaliP28240.
    SMRiP28240. Positions 22-534.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Region

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Regioni106 – 1083Substrate bindingBy similarity
    Regioni218 – 2192Substrate bindingBy similarity
    Regioni437 – 4415Substrate bindingBy similarity

    Sequence similaritiesi

    Phylogenomic databases

    eggNOGiCOG2224.
    GeneTreeiENSGT00510000053163.
    HOGENOMiHOG000238475.
    InParanoidiP28240.
    KOiK01637.
    OMAiEMEQGVD.
    OrthoDBiEOG73Z331.

    Family and domain databases

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

    Sequencei

    Sequence statusi: Complete.

    P28240-1 [UniParc]FASTAAdd to basket

    « Hide

            10         20         30         40         50
    MPIPVGNTKN DFAALQAKLD ADAAEIEKWW SDSRWSKTKR NYSARDIAVR
    60 70 80 90 100
    RGTFPPIEYP SSVMARKLFK VLEKHHNEGT VSKTFGALDP VQISQMAKYL
    110 120 130 140 150
    DTIYISGWQC SSTASTSNEP GPDLADYPMD TVPNKVEHLF KAQLFHDRKQ
    160 170 180 190 200
    LEARSKAKSQ EELDEMGAPI DYLTPIVADA DAGHGGLTAV FKLTKMFIER
    210 220 230 240 250
    GAAGIHMEDQ TSTNKKCGHM AGRCVIPVQE HVNRLVTIRM CADIMHSDLI
    260 270 280 290 300
    VVARTDSEAA TLISSTIDTR DHYFIVGATN PNIEPFAEVL NDAIMSGASG
    310 320 330 340 350
    QELADIEQKW CRDAGLKLFH EAVIDEIERS ALSNKQELIK KFTSKVGPLT
    360 370 380 390 400
    ETSHREAKKL AKEILGHEIF FDWELPRVRE GLYRYRGGTQ CSIMRARAFA
    410 420 430 440 450
    PYADLVWMES NYPDFQQAKE FAEGVKEKFP DQWLAYNLSP SFNWPKAMSV
    460 470 480 490 500
    DEQHTFIQRL GDLGYIWQFI TLAGLHTNAL AVHNFSRDFA KDGMKAYAQN
    510 520 530 540 550
    VQQREMDDGV DVLKHQKWSG AEYIDGLLKL AQGGVSATAA MGTGVTEDQF

    KENGVKK
    Length:557
    Mass (Da):62,409
    Last modified:December 1, 1992 - v1
    Checksum:i15CC5A169CCEBE8B
    GO

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    X61271 Genomic DNA. Translation: CAA43575.1.
    X65554 Genomic DNA. Translation: CAA46523.1.
    U18813 Genomic DNA. Translation: AAB64601.1.
    BK006939 Genomic DNA. Translation: DAA07724.1.
    PIRiS22386. WZBYI.
    RefSeqiNP_010987.3. NM_001178956.3.

    Genome annotation databases

    EnsemblFungiiYER065C; YER065C; YER065C.
    GeneIDi856794.
    KEGGisce:YER065C.

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    X61271 Genomic DNA. Translation: CAA43575.1.
    X65554 Genomic DNA. Translation: CAA46523.1.
    U18813 Genomic DNA. Translation: AAB64601.1.
    BK006939 Genomic DNA. Translation: DAA07724.1.
    PIRiS22386. WZBYI.
    RefSeqiNP_010987.3. NM_001178956.3.

    3D structure databases

    ProteinModelPortaliP28240.
    SMRiP28240. Positions 22-534.
    ModBaseiSearch...
    MobiDBiSearch...

    Protein-protein interaction databases

    BioGridi36807. 31 interactions.
    DIPiDIP-1663N.
    IntActiP28240. 2 interactions.
    MINTiMINT-400647.
    STRINGi4932.YER065C.

    Proteomic databases

    MaxQBiP28240.
    PaxDbiP28240.
    PeptideAtlasiP28240.

    Protocols and materials databases

    Structural Biology KnowledgebaseSearch...

    Genome annotation databases

    EnsemblFungiiYER065C; YER065C; YER065C.
    GeneIDi856794.
    KEGGisce:YER065C.

    Organism-specific databases

    CYGDiYER065c.
    EuPathDBiFungiDB:YER065C.
    SGDiS000000867. ICL1.

    Phylogenomic databases

    eggNOGiCOG2224.
    GeneTreeiENSGT00510000053163.
    HOGENOMiHOG000238475.
    InParanoidiP28240.
    KOiK01637.
    OMAiEMEQGVD.
    OrthoDBiEOG73Z331.

    Enzyme and pathway databases

    UniPathwayiUPA00703; UER00719.
    BioCyciYEAST:YER065C-MONOMER.
    SABIO-RKP28240.

    Miscellaneous databases

    NextBioi983030.
    PROiP28240.

    Gene expression databases

    GenevestigatoriP28240.

    Family and domain databases

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

    Publicationsi

    « Hide 'large scale' publications
    1. Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], FUNCTION, CATALYTIC ACTIVITY, DISRUPTION PHENOTYPE.
    2. "Structure and regulation of the isocitrate lyase gene ICL1 from the yeast Saccharomyces cerevisiae."
      Schoeler A., Schueller H.-J.
      Curr. Genet. 23:375-381(1993) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], INDUCTION.
      Strain: DBY939.
    3. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
      Strain: ATCC 204508 / S288c.
    4. Cited for: GENOME REANNOTATION.
      Strain: ATCC 204508 / S288c.
    5. "Production of pyruvate and succinate by action of isocitrate lyase on alpha-methylisocitrate."
      McFadden B.A., Rose I.A., Williams J.O.
      Arch. Biochem. Biophys. 148:84-88(1972) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES.
    6. "Glucose-stimulated phosphorylation of yeast isocitrate lyase in vivo."
      Lopez-Boado Y.S., Herrero P., Fernandez M.-T., Fernandez R., Moreno F.
      J. Gen. Microbiol. 134:2499-2505(1988) [PubMed] [Europe PMC] [Abstract]
      Cited for: PHOSPHORYLATION, ENZYME REGULATION, INDUCTION.
    7. "Purification of isocitrate lyase from Saccharomyces cerevisiae."
      Lopez-Boado Y.S., Herrero P., Fernandez M.-T., Fernandez R., Moreno F.
      Yeast 4:41-46(1988) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, SUBUNIT.
    8. "Localization and targeting of isocitrate lyases in Saccharomyces cerevisiae."
      Taylor K.M., Kaplan C.P., Gao X., Baker A.
      Biochem. J. 319:255-262(1996) [PubMed] [Europe PMC] [Abstract]
      Cited for: SUBCELLULAR LOCATION.
    9. "Glucose-induced inactivation of isocitrate lyase in Saccharomyces cerevisiae is mediated by the cAMP-dependent protein kinase catalytic subunits Tpk1 and Tpk2."
      Ordiz I., Herrero P., Rodicio R., Moreno F.
      FEBS Lett. 385:43-46(1996) [PubMed] [Europe PMC] [Abstract]
      Cited for: MUTAGENESIS OF THR-53.
    10. "Molecular genetics of ICL2, encoding a non-functional isocitrate lyase in Saccharomyces cerevisiae."
      Heinisch J.J., Valdes E., Alvarez J., Rodicio R.
      Yeast 12:1285-1295(1996) [PubMed] [Europe PMC] [Abstract]
      Cited for: MUTAGENESIS OF LYS-216 AND MET-220.
    11. "Isocitrate lyase localisation in Saccharomyces cerevisiae cells."
      Chaves R.S., Herrero P., Ordiz I., Angeles del Brio M., Moreno F.
      Gene 198:165-169(1997) [PubMed] [Europe PMC] [Abstract]
      Cited for: SUBCELLULAR LOCATION.
    12. "A 27 kDa protein binds to a positive and a negative regulatory sequence in the promoter of the ICL1 gene from Saccharomyces cerevisiae."
      Ordiz I., Herrero P., Rodicio R., Gancedo J.M., Moreno F.
      Biochem. J. 329:383-388(1998) [PubMed] [Europe PMC] [Abstract]
      Cited for: INDUCTION.
    13. "Deregulation of gluconeogenic structural genes by variants of the transcriptional activator Cat8p of the yeast Saccharomyces cerevisiae."
      Rahner A., Hiesinger M., Schueller H.-J.
      Mol. Microbiol. 34:146-156(1999) [PubMed] [Europe PMC] [Abstract]
      Cited for: INDUCTION.
    14. "The glyoxylate cycle is required for fungal virulence."
      Lorenz M.C., Fink G.R.
      Nature 412:83-86(2001) [PubMed] [Europe PMC] [Abstract]
      Cited for: DISRUPTION PHENOTYPE, FUNCTION.
    15. Cited for: IDENTIFICATION BY MASS SPECTROMETRY, SUBCELLULAR LOCATION.
    16. "Glucose controls multiple processes in Saccharomyces cerevisiae through diverse combinations of signaling pathways."
      Belinchon M.M., Gancedo J.M.
      FEMS Yeast Res. 7:808-818(2007) [PubMed] [Europe PMC] [Abstract]
      Cited for: INDUCTION.
    17. "The TOR complex 1 is distributed in endosomes and in retrograde vesicles that form from the vacuole membrane and plays an important role in the vacuole import and degradation pathway."
      Brown C.R., Hung G.C., Dunton D., Chiang H.L.
      J. Biol. Chem. 285:23359-23370(2010) [PubMed] [Europe PMC] [Abstract]
      Cited for: SUBCELLULAR LOCATION.
    18. "TCA cycle-independent acetate metabolism via the glyoxylate cycle in Saccharomyces cerevisiae."
      Lee Y.J., Jang J.W., Kim K.J., Maeng P.J.
      Yeast 28:153-166(2011) [PubMed] [Europe PMC] [Abstract]
      Cited for: DISRUPTION PHENOTYPE.
    19. "Profiling of cytosolic and peroxisomal acetyl-CoA metabolism in Saccharomyces cerevisiae."
      Chen Y., Siewers V., Nielsen J.
      PLoS ONE 7:E42475-E42475(2012) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION.
    20. "Lack of Sir2 increases acetate consumption and decreases extracellular pro-aging factors."
      Casatta N., Porro A., Orlandi I., Brambilla L., Vai M.
      Biochim. Biophys. Acta 1833:593-601(2013) [PubMed] [Europe PMC] [Abstract]
      Cited for: CATALYTIC ACTIVITY, FUNCTION, DISRUPTION PHENOTYPE.
    21. "Ethanol and acetate acting as carbon/energy sources negatively affect yeast chronological aging."
      Orlandi I., Ronzulli R., Casatta N., Vai M.
      Oxid. Med. Cell. Longev. 2013:802870-802870(2013) [PubMed] [Europe PMC] [Abstract]
      Cited for: DISRUPTION PHENOTYPE.
    22. "The endocytosis gene END3 is essential for the glucose-induced rapid decline of small vesicles in the extracellular fraction in Saccharomyces cerevisiae."
      Giardina B.J., Stein K., Chiang H.L.
      J. Extracell. Vesicles 3:0-0(2014) [PubMed] [Europe PMC] [Abstract]
      Cited for: IDENTIFICATION BY MASS SPECTROMETRY, SUBCELLULAR LOCATION.
    23. "Glucose induces rapid changes in the secretome of Saccharomyces cerevisiae."
      Giardina B.J., Stanley B.A., Chiang H.L.
      Proteome Sci. 12:9-9(2014) [PubMed] [Europe PMC] [Abstract]
      Cited for: SUBCELLULAR LOCATION.

    Entry informationi

    Entry nameiACEA_YEAST
    AccessioniPrimary (citable) accession number: P28240
    Secondary accession number(s): D3DLX0
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: December 1, 1992
    Last sequence update: December 1, 1992
    Last modified: May 27, 2015
    This is version 133 of the entry and version 1 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programFungal Protein Annotation Program

    Miscellaneousi

    Miscellaneous

    Yeast isocitrate lyase is the only eukaryotic member of this family that is located in the cytoplasm, instead of being targeted to the peroxisome or the glyoxysome.1 Publication

    Keywords - Technical termi

    Complete proteome, Reference proteome

    Documents

    1. PATHWAY comments
      Index of metabolic and biosynthesis pathways
    2. SIMILARITY comments
      Index of protein domains and families
    3. Yeast
      Yeast (Saccharomyces cerevisiae): entries, gene names and cross-references to SGD
    4. Yeast chromosome V
      Yeast (Saccharomyces cerevisiae) chromosome V: entries and gene names

    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.