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P28240 (ACEA_YEAST) Reviewed, UniProtKB/Swiss-Prot

Last modified February 19, 2014. Version 125. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (4) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Isocitrate lyase

Short name=ICL
EC=4.1.3.1
Alternative name(s):
Threo-D(S)-isocitrate glyoxylate-lyase
Short name=Isocitrase
Short name=Isocitratase
Gene names
Name:ICL1
Ordered Locus Names:YER065C
OrganismSaccharomyces cerevisiae (strain ATCC 204508 / S288c) (Baker's yeast) [Reference proteome]
Taxonomic identifier559292 [NCBI]
Taxonomic lineageEukaryotaFungiDikaryaAscomycotaSaccharomycotinaSaccharomycetesSaccharomycetalesSaccharomycetaceaeSaccharomyces

Protein attributes

Sequence length557 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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.

Catalytic activity

Isocitrate = succinate + glyoxylate.

Enzyme regulation

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

Pathway

Carbohydrate metabolism; glyoxylate cycle; (S)-malate from isocitrate: step 1/2.

Subunit structure

Homotetramer. Ref.7

Subcellular location

Cytoplasm Ref.8 Ref.11.

Induction

Repressed by glucose and induced by ethanol via the transcriptional activator CAT8. Ref.2 Ref.6 Ref.12

Post-translational modification

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). Ref.6

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.

The Pseudomonas indigofera ortholog enzyme can be inactivated by beta-bromopyruvate.

Sequence similarities

Belongs to the isocitrate lyase/PEP mutase superfamily. Isocitrate lyase family.

Biophysicochemical properties

Kinetic parameters:

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

KM=1.4 mM for threo-D(S)-isocitrate (at pH 7.0) Ref.5 Ref.7

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

pH dependence:

Optimum pH is 7.

Temperature dependence:

Thermostable for 60 minutes up to 50 degrees Celsius.

Ontologies

Keywords
   Biological processGlyoxylate bypass
Tricarboxylic acid cycle
   Cellular componentCytoplasm
   Molecular functionLyase
   PTMPhosphoprotein
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processglyoxylate cycle

Traceable author statement PubMed 11092862. Source: SGD

tricarboxylic acid cycle

Inferred from electronic annotation. Source: UniProtKB-KW

   Cellular_componentcytoplasm

Inferred from electronic annotation. Source: UniProtKB-SubCell

   Molecular_functionisocitrate lyase activity

Inferred from mutant phenotype Ref.1. Source: SGD

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 557557Isocitrate lyase
PRO_0000068799

Sites

Active site2171 Probable

Amino acid modifications

Modified residue531Phosphothreonine Potential

Experimental info

Mutagenesis531T → A: Abolishes short-term enzyme inactivation by glucose addition. Ref.9
Mutagenesis2161K → R: Reduces activity by 45%; when associated with L-220. Ref.10
Mutagenesis2201M → L: Reduces activity by 45%; when associated with R-216. Ref.10

Sequences

Sequence LengthMass (Da)Tools
P28240 [UniParc].

Last modified December 1, 1992. Version 1.
Checksum: 15CC5A169CCEBE8B

FASTA55762,409
        10         20         30         40         50         60 
MPIPVGNTKN DFAALQAKLD ADAAEIEKWW SDSRWSKTKR NYSARDIAVR RGTFPPIEYP 

        70         80         90        100        110        120 
SSVMARKLFK VLEKHHNEGT VSKTFGALDP VQISQMAKYL DTIYISGWQC SSTASTSNEP 

       130        140        150        160        170        180 
GPDLADYPMD TVPNKVEHLF KAQLFHDRKQ LEARSKAKSQ EELDEMGAPI DYLTPIVADA 

       190        200        210        220        230        240 
DAGHGGLTAV FKLTKMFIER GAAGIHMEDQ TSTNKKCGHM AGRCVIPVQE HVNRLVTIRM 

       250        260        270        280        290        300 
CADIMHSDLI VVARTDSEAA TLISSTIDTR DHYFIVGATN PNIEPFAEVL NDAIMSGASG 

       310        320        330        340        350        360 
QELADIEQKW CRDAGLKLFH EAVIDEIERS ALSNKQELIK KFTSKVGPLT ETSHREAKKL 

       370        380        390        400        410        420 
AKEILGHEIF FDWELPRVRE GLYRYRGGTQ CSIMRARAFA PYADLVWMES NYPDFQQAKE 

       430        440        450        460        470        480 
FAEGVKEKFP DQWLAYNLSP SFNWPKAMSV DEQHTFIQRL GDLGYIWQFI TLAGLHTNAL 

       490        500        510        520        530        540 
AVHNFSRDFA KDGMKAYAQN VQQREMDDGV DVLKHQKWSG AEYIDGLLKL AQGGVSATAA 

       550 
MGTGVTEDQF KENGVKK 

« Hide

References

« Hide 'large scale' references
[1]"The ICL1 gene from Saccharomyces cerevisiae."
Fernandez E., Moreno F., Rodicio R.
Eur. J. Biochem. 204:983-990(1992) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[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]"The nucleotide sequence of Saccharomyces cerevisiae chromosome V."
Dietrich F.S., Mulligan J.T., Hennessy K.M., Yelton M.A., Allen E., Araujo R., Aviles E., Berno A., Brennan T., Carpenter J., Chen E., Cherry J.M., Chung E., Duncan M., Guzman E., Hartzell G., Hunicke-Smith S., Hyman R.W. expand/collapse author list , Kayser A., Komp C., Lashkari D., Lew H., Lin D., Mosedale D., Nakahara K., Namath A., Norgren R., Oefner P., Oh C., Petel F.X., Roberts D., Sehl P., Schramm S., Shogren T., Smith V., Taylor P., Wei Y., Botstein D., Davis R.W.
Nature 387:78-81(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
Strain: ATCC 204508 / S288c.
[4]Saccharomyces Genome Database
Submitted (DEC-2009) to the EMBL/GenBank/DDBJ databases
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: CHARACTERIZATION, 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, 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: 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]"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.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
X61271 Genomic DNA. Translation: CAA43575.1.
X65554 Genomic DNA. Translation: CAA46523.1.
U18813 Genomic DNA. Translation: AAB64601.1.
BK006939 Genomic DNA. Translation: DAA07724.1.
PIRWZBYI. S22386.
RefSeqNP_010987.3. NM_001178956.3.

3D structure databases

ProteinModelPortalP28240.
SMRP28240. Positions 22-534.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid36807. 29 interactions.
DIPDIP-1663N.
IntActP28240. 2 interactions.
MINTMINT-400647.
STRING4932.YER065C.

Proteomic databases

PaxDbP28240.
PeptideAtlasP28240.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblFungiYER065C; YER065C; YER065C.
GeneID856794.
KEGGsce:YER065C.

Organism-specific databases

CYGDYER065c.
SGDS000000867. ICL1.

Phylogenomic databases

eggNOGCOG2224.
GeneTreeENSGT00510000053163.
HOGENOMHOG000238475.
KOK01637.
OMACAINRAI.
OrthoDBEOG73Z331.

Enzyme and pathway databases

BioCycYEAST:YER065C-MONOMER.
SABIO-RKP28240.
UniPathwayUPA00703; UER00719.

Gene expression databases

GenevestigatorP28240.

Family and domain databases

Gene3D3.20.20.60. 2 hits.
InterProIPR006254. Isocitrate_lyase.
IPR000918. Isocitrate_lyase/Pmutase.
IPR018523. Isocitrate_lyase_ph_CS.
IPR015813. Pyrv/PenolPyrv_Kinase-like_dom.
[Graphical view]
PANTHERPTHR21631:SF3. PTHR21631:SF3. 1 hit.
PfamPF00463. ICL. 1 hit.
[Graphical view]
PIRSFPIRSF001362. Isocit_lyase. 1 hit.
SUPFAMSSF51621. SSF51621. 1 hit.
TIGRFAMsTIGR01346. isocit_lyase. 1 hit.
PROSITEPS00161. ISOCITRATE_LYASE. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

NextBio983030.

Entry information

Entry nameACEA_YEAST
AccessionPrimary (citable) accession number: P28240
Secondary accession number(s): D3DLX0
Entry history
Integrated into UniProtKB/Swiss-Prot: December 1, 1992
Last sequence update: December 1, 1992
Last modified: February 19, 2014
This is version 125 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programFungal Protein Annotation Program

Relevant documents

Yeast chromosome V

Yeast (Saccharomyces cerevisiae) chromosome V: entries and gene names

Yeast

Yeast (Saccharomyces cerevisiae): entries, gene names and cross-references to SGD

SIMILARITY comments

Index of protein domains and families

PATHWAY comments

Index of metabolic and biosynthesis pathways