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Protein

Homoisocitrate dehydrogenase, mitochondrial

Gene

LYS12

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 NAD+-dependent conversion of homoisocitrate to alpha-ketoadipate.1 Publication

Catalytic activityi

(1R,2S)-1-hydroxybutane-1,2,4-tricarboxylate + NAD+ = 2-oxoadipate + CO2 + NADH.3 Publications

Cofactori

Mg2+2 Publications, Mn2+2 PublicationsNote: Binds 1 Mg(2+) or Mn2+ ion per subunit.2 Publications

Enzyme regulationi

Inhibited by the reaction product NADH. Inhibited by oxalate; this is a non-competitive inhibitor.1 Publication

Kineticsi

The KM for homoisocitrate is lower than 10 µM.

  1. KM=1.5 mM for 2-oxoadipate1 Publication
  2. KM=330 µM for NAD+1 Publication
  3. KM=65 µM for NADH1 Publication

    pH dependencei

    Optimum pH is 8.3-8.8 for the forward reaction, and 7 for the reverse reaction.1 Publication

    Pathway:iL-lysine biosynthesis via AAA pathway

    This protein is involved in step 4 of the subpathway that synthesizes L-alpha-aminoadipate from 2-oxoglutarate.
    Proteins known to be involved in the 5 steps of the subpathway in this organism are:
    1. Homocitrate synthase, cytosolic isozyme (LYS20), Homocitrate synthase, mitochondrial (LYS21)
    2. Homocitrate dehydratase, mitochondrial (ACO2)
    3. Homoaconitase, mitochondrial (LYS4)
    4. Homoisocitrate dehydrogenase, mitochondrial (LYS12)
    5. Aromatic/aminoadipate aminotransferase 1 (ARO8)
    This subpathway is part of the pathway L-lysine biosynthesis via AAA pathway, which is itself part of Amino-acid biosynthesis.
    View all proteins of this organism that are known to be involved in the subpathway that synthesizes L-alpha-aminoadipate from 2-oxoglutarate, the pathway L-lysine biosynthesis via AAA pathway and in Amino-acid biosynthesis.

    Sites

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Binding sitei114 – 1141SubstrateBy similarity
    Binding sitei124 – 1241SubstrateBy similarity
    Binding sitei143 – 1431SubstrateBy similarity
    Sitei150 – 1501Critical for catalysis
    Sitei206 – 2061Critical for catalysis
    Metal bindingi243 – 2431Magnesium or manganeseBy similarity
    Binding sitei243 – 2431SubstrateBy similarity
    Metal bindingi267 – 2671Magnesium or manganeseBy similarity
    Metal bindingi271 – 2711Magnesium or manganeseBy similarity

    GO - Molecular functioni

    • homoisocitrate dehydrogenase activity Source: SGD
    • magnesium ion binding Source: InterPro
    • NAD binding Source: InterPro

    GO - Biological processi

    • lysine biosynthetic process Source: SGD
    • lysine biosynthetic process via aminoadipic acid Source: UniProtKB-UniPathway
    Complete GO annotation...

    Keywords - Molecular functioni

    Oxidoreductase

    Keywords - Biological processi

    Amino-acid biosynthesis, Lysine biosynthesis

    Keywords - Ligandi

    Magnesium, Manganese, Metal-binding, NAD

    Enzyme and pathway databases

    BioCyciYEAST:YIL094C-MONOMER.
    UniPathwayiUPA00033; UER00030.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Homoisocitrate dehydrogenase, mitochondrial (EC:1.1.1.87)
    Short name:
    HIcDH
    Gene namesi
    Name:LYS12
    Synonyms:LYS10, LYS11
    Ordered Locus Names:YIL094C
    ORF Names:YI9910.02C
    OrganismiSaccharomyces cerevisiae (strain ATCC 204508 / S288c) (Baker's yeast)
    Taxonomic identifieri559292 [NCBI]
    Taxonomic lineageiEukaryotaFungiDikaryaAscomycotaSaccharomycotinaSaccharomycetesSaccharomycetalesSaccharomycetaceaeSaccharomyces
    ProteomesiUP000002311 Componenti: Chromosome IX

    Organism-specific databases

    CYGDiYIL094c.
    EuPathDBiFungiDB:YIL094C.
    SGDiS000001356. LYS12.

    Subcellular locationi

    GO - Cellular componenti

    Complete GO annotation...

    Keywords - Cellular componenti

    Mitochondrion

    Pathology & Biotechi

    Mutagenesis

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Mutagenesisi150 – 1501Y → F: Strongly reduced enzyme activity. 1 Publication
    Mutagenesisi206 – 2061K → M: Strongly reduced enzyme activity. 1 Publication

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Transit peptidei1 – 2222MitochondrionSequence AnalysisAdd
    BLAST
    Chaini23 – 371349Homoisocitrate dehydrogenase, mitochondrialPRO_0000043097Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Modified residuei98 – 981Phosphoserine1 Publication

    Keywords - PTMi

    Phosphoprotein

    Proteomic databases

    MaxQBiP40495.
    PaxDbiP40495.
    PeptideAtlasiP40495.

    Expressioni

    Inductioni

    Activity is repressed 4-fold by lysine.1 Publication

    Interactioni

    Protein-protein interaction databases

    BioGridi34898. 71 interactions.
    DIPiDIP-4162N.
    IntActiP40495. 91 interactions.
    MINTiMINT-491742.

    Structurei

    3D structure databases

    ProteinModelPortaliP40495.
    SMRiP40495. Positions 22-371.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Sequence similaritiesi

    Keywords - Domaini

    Transit peptide

    Phylogenomic databases

    eggNOGiCOG0473.
    GeneTreeiENSGT00550000076087.
    HOGENOMiHOG000021111.
    InParanoidiP40495.
    KOiK05824.
    OMAiRCGDAIP.
    OrthoDBiEOG7R83BB.

    Family and domain databases

    Gene3Di3.40.718.10. 1 hit.
    InterProiIPR019818. IsoCit/isopropylmalate_DH_CS.
    IPR001804. Isocitrate/isopropylmalate_DH.
    IPR024084. IsoPropMal-DH-like_dom.
    [Graphical view]
    PANTHERiPTHR11835. PTHR11835. 1 hit.
    PfamiPF00180. Iso_dh. 1 hit.
    [Graphical view]
    PROSITEiPS00470. IDH_IMDH. 1 hit.
    [Graphical view]

    Sequencei

    Sequence statusi: Complete.

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

    P40495-1 [UniParc]FASTAAdd to basket

    « Hide

            10         20         30         40         50
    MFRSVATRLS ACRGLASNAA RKSLTIGLIP GDGIGKEVIP AGKQVLENLN
    60 70 80 90 100
    SKHGLSFNFI DLYAGFQTFQ ETGKALPDET VKVLKEQCQG ALFGAVQSPT
    110 120 130 140 150
    TKVEGYSSPI VALRREMGLF ANVRPVKSVE GEKGKPIDMV IVRENTEDLY
    160 170 180 190 200
    IKIEKTYIDK ATGTRVADAT KRISEIATRR IATIALDIAL KRLQTRGQAT
    210 220 230 240 250
    LTVTHKSNVL SQSDGLFREI CKEVYESNKD KYGQIKYNEQ IVDSMVYRLF
    260 270 280 290 300
    REPQCFDVIV APNLYGDILS DGAAALVGSL GVVPSANVGP EIVIGEPCHG
    310 320 330 340 350
    SAPDIAGKGI ANPIATIRST ALMLEFLGHN EAAQDIYKAV DANLREGSIK
    360 370
    TPDLGGKAST QQVVDDVLSR L
    Length:371
    Mass (Da):40,069
    Last modified:February 1, 1995 - v1
    Checksum:i43CAFA86F75ED3C6
    GO

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    Z46728 Genomic DNA. Translation: CAA86700.1.
    BK006942 Genomic DNA. Translation: DAA08459.1.
    PIRiS49786.
    RefSeqiNP_012172.1. NM_001179442.1.

    Genome annotation databases

    EnsemblFungiiYIL094C; YIL094C; YIL094C.
    GeneIDi854714.
    KEGGisce:YIL094C.

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    Z46728 Genomic DNA. Translation: CAA86700.1.
    BK006942 Genomic DNA. Translation: DAA08459.1.
    PIRiS49786.
    RefSeqiNP_012172.1. NM_001179442.1.

    3D structure databases

    ProteinModelPortaliP40495.
    SMRiP40495. Positions 22-371.
    ModBaseiSearch...
    MobiDBiSearch...

    Protein-protein interaction databases

    BioGridi34898. 71 interactions.
    DIPiDIP-4162N.
    IntActiP40495. 91 interactions.
    MINTiMINT-491742.

    Chemistry

    BindingDBiP40495.
    ChEMBLiCHEMBL1075252.

    Proteomic databases

    MaxQBiP40495.
    PaxDbiP40495.
    PeptideAtlasiP40495.

    Protocols and materials databases

    Structural Biology KnowledgebaseSearch...

    Genome annotation databases

    EnsemblFungiiYIL094C; YIL094C; YIL094C.
    GeneIDi854714.
    KEGGisce:YIL094C.

    Organism-specific databases

    CYGDiYIL094c.
    EuPathDBiFungiDB:YIL094C.
    SGDiS000001356. LYS12.

    Phylogenomic databases

    eggNOGiCOG0473.
    GeneTreeiENSGT00550000076087.
    HOGENOMiHOG000021111.
    InParanoidiP40495.
    KOiK05824.
    OMAiRCGDAIP.
    OrthoDBiEOG7R83BB.

    Enzyme and pathway databases

    UniPathwayiUPA00033; UER00030.
    BioCyciYEAST:YIL094C-MONOMER.

    Miscellaneous databases

    ChiTaRSiLYS12. yeast.
    NextBioi977383.
    PROiP40495.

    Family and domain databases

    Gene3Di3.40.718.10. 1 hit.
    InterProiIPR019818. IsoCit/isopropylmalate_DH_CS.
    IPR001804. Isocitrate/isopropylmalate_DH.
    IPR024084. IsoPropMal-DH-like_dom.
    [Graphical view]
    PANTHERiPTHR11835. PTHR11835. 1 hit.
    PfamiPF00180. Iso_dh. 1 hit.
    [Graphical view]
    PROSITEiPS00470. IDH_IMDH. 1 hit.
    [Graphical view]
    ProtoNetiSearch...

    Publicationsi

    « Hide 'large scale' publications
    1. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
      Strain: ATCC 204508 / S288c.
    2. Cited for: GENOME REANNOTATION.
      Strain: ATCC 204508 / S288c.
    3. Bienvenut W.V., Peters C.
      Submitted (JUN-2005) to UniProtKB
      Cited for: PROTEIN SEQUENCE OF 23-36; 103-114; 116-127; 181-192; 237-248; 309-318 AND 346-370, IDENTIFICATION BY MASS SPECTROMETRY.
    4. "Enzymatic formation of alpha-ketoadipic acid from homoisocitric acid."
      Strassman M., Ceci L.N.
      J. Biol. Chem. 240:4357-4361(1965) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, CATALYTIC ACTIVITY.
    5. Cited for: BIOPHYSICOCHEMICAL PROPERTIES.
    6. "General and specific controls of lysine biosynthesis in Saccharomyces cerevisiae."
      Urrestarazu L.A., Borell C.W., Bhattacharjee J.K.
      Curr. Genet. 9:341-344(1985) [PubMed] [Europe PMC] [Abstract]
      Cited for: INDUCTION.
    7. "Linking genome and proteome by mass spectrometry: large-scale identification of yeast proteins from two dimensional gels."
      Shevchenko A., Jensen O.N., Podtelejnikov A.V., Sagliocco F., Wilm M., Vorm O., Mortensen P., Shevchenko A., Boucherie H., Mann M.
      Proc. Natl. Acad. Sci. U.S.A. 93:14440-14445(1996) [PubMed] [Europe PMC] [Abstract]
      Cited for: IDENTIFICATION BY MASS SPECTROMETRY.
    8. Cited for: SUBCELLULAR LOCATION [LARGE SCALE ANALYSIS].
    9. Cited for: LEVEL OF PROTEIN EXPRESSION [LARGE SCALE ANALYSIS].
    10. Cited for: SUBCELLULAR LOCATION [LARGE SCALE ANALYSIS].
      Strain: ATCC 76625 / YPH499.
    11. "Complete kinetic mechanism of homoisocitrate dehydrogenase from Saccharomyces cerevisiae."
      Lin Y., Alguindigue S.S., Volkman J., Nicholas K.M., West A.H., Cook P.F.
      Biochemistry 46:890-898(2007) [PubMed] [Europe PMC] [Abstract]
      Cited for: CATALYTIC ACTIVITY, COFACTOR, ENZYME REGULATION.
    12. "A multidimensional chromatography technology for in-depth phosphoproteome analysis."
      Albuquerque C.P., Smolka M.B., Payne S.H., Bafna V., Eng J., Zhou H.
      Mol. Cell. Proteomics 7:1389-1396(2008) [PubMed] [Europe PMC] [Abstract]
      Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-98, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    13. "Site-directed mutagenesis as a probe of the acid-base catalytic mechanism of homoisocitrate dehydrogenase from Saccharomyces cerevisiae."
      Lin Y., West A.H., Cook P.F.
      Biochemistry 48:7305-7312(2009) [PubMed] [Europe PMC] [Abstract]
      Cited for: CATALYTIC ACTIVITY, COFACTOR, MUTAGENESIS OF TYR-150 AND LYS-206.

    Entry informationi

    Entry nameiLYS12_YEAST
    AccessioniPrimary (citable) accession number: P40495
    Secondary accession number(s): D6VVJ3
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: February 1, 1995
    Last sequence update: February 1, 1995
    Last modified: July 22, 2015
    This is version 128 of the entry and version 1 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programFungal Protein Annotation Program

    Miscellaneousi

    Miscellaneous

    Present with 19079 molecules/cell in log phase SD medium.1 Publication

    Keywords - Technical termi

    Complete proteome, Direct protein sequencing, 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 IX
      Yeast (Saccharomyces cerevisiae) chromosome IX: 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.