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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 Mg2+ 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

    Pathwayi: L-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)DescriptionActionsGraphical viewLength
    Binding sitei114SubstrateBy similarity1
    Binding sitei124SubstrateBy similarity1
    Binding sitei143SubstrateBy similarity1
    Sitei150Critical for catalysis1
    Sitei206Critical for catalysis1
    Metal bindingi243Magnesium or manganeseBy similarity1
    Binding sitei243SubstrateBy similarity1
    Metal bindingi267Magnesium or manganeseBy similarity1
    Metal bindingi271Magnesium or manganeseBy similarity1

    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
    Proteomesi
    • UP000002311 Componenti: Chromosome IX

    Organism-specific databases

    EuPathDBiFungiDB:YIL094C.
    SGDiS000001356. LYS12.

    Subcellular locationi

    GO - Cellular componenti

    Complete GO annotation...

    Keywords - Cellular componenti

    Mitochondrion

    Pathology & Biotechi

    Mutagenesis

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Mutagenesisi150Y → F: Strongly reduced enzyme activity. 1 Publication1
    Mutagenesisi206K → M: Strongly reduced enzyme activity. 1 Publication1

    Chemistry databases

    ChEMBLiCHEMBL1075252.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Transit peptidei1 – 22MitochondrionSequence analysisAdd BLAST22
    ChainiPRO_000004309723 – 371Homoisocitrate dehydrogenase, mitochondrialAdd BLAST349

    Amino acid modifications

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Modified residuei98PhosphoserineCombined sources1

    Keywords - PTMi

    Phosphoprotein

    Proteomic databases

    MaxQBiP40495.
    PRIDEiP40495.

    PTM databases

    iPTMnetiP40495.

    Expressioni

    Inductioni

    Activity is repressed 4-fold by lysine.1 Publication

    Interactioni

    Protein-protein interaction databases

    BioGridi34898. 73 interactors.
    DIPiDIP-4162N.
    IntActiP40495. 91 interactors.
    MINTiMINT-491742.

    Chemistry databases

    BindingDBiP40495.

    Structurei

    3D structure databases

    ProteinModelPortaliP40495.
    SMRiP40495.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Sequence similaritiesi

    Keywords - Domaini

    Transit peptide

    Phylogenomic databases

    GeneTreeiENSGT00550000076087.
    HOGENOMiHOG000021111.
    InParanoidiP40495.
    KOiK05824.
    OMAiLMLEFMG.
    OrthoDBiEOG092C2YAZ.

    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]
    SMARTiSM01329. 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.
    ModBaseiSearch...
    MobiDBiSearch...

    Protein-protein interaction databases

    BioGridi34898. 73 interactors.
    DIPiDIP-4162N.
    IntActiP40495. 91 interactors.
    MINTiMINT-491742.

    Chemistry databases

    BindingDBiP40495.
    ChEMBLiCHEMBL1075252.

    PTM databases

    iPTMnetiP40495.

    Proteomic databases

    MaxQBiP40495.
    PRIDEiP40495.

    Protocols and materials databases

    Structural Biology KnowledgebaseSearch...

    Genome annotation databases

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

    Organism-specific databases

    EuPathDBiFungiDB:YIL094C.
    SGDiS000001356. LYS12.

    Phylogenomic databases

    GeneTreeiENSGT00550000076087.
    HOGENOMiHOG000021111.
    InParanoidiP40495.
    KOiK05824.
    OMAiLMLEFMG.
    OrthoDBiEOG092C2YAZ.

    Enzyme and pathway databases

    UniPathwayiUPA00033; UER00030.
    BioCyciYEAST:YIL094C-MONOMER.

    Miscellaneous databases

    ChiTaRSiLYS12. yeast.
    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]
    SMARTiSM01329. Iso_dh. 1 hit.
    [Graphical view]
    PROSITEiPS00470. IDH_IMDH. 1 hit.
    [Graphical view]
    ProtoNetiSearch...

    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: November 2, 2016
    This is version 140 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

    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.