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Protein

Homoisocitrate dehydrogenase

Gene

hicd

Organism
Thermus thermophilus (strain HB27 / ATCC BAA-163 / DSM 7039)
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. In addition, has high activity with citrate, but is inactive with 3-isopropylmalate.2 Publications

Catalytic activityi

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

Cofactori

Mg2+By similarity, Mn2+By similarityNote: Binds 1 Mg2+ or Mn2+ ion per subunit.By similarity

Kineticsi

  1. KM=7486 µM for homoisocitrate1 Publication
  2. KM=405 µM for isocitrate1 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.1 Publication
    Proteins known to be involved in the 5 steps of the subpathway in this organism are:
    1. Homocitrate synthase (lys20)
    2. no protein annotated in this organism
    3. Homoaconitase large subunit (hacA), Homoaconitase small subunit (hacB)
    4. Homoisocitrate dehydrogenase (hicd)
    5. 2-aminoadipate transaminase (lysN)
    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
    Sitei85Important for substrate specificity and discrimination against 3-isopropylmalate1
    Binding sitei88SubstrateBy similarity1
    Binding sitei98SubstrateBy similarity1
    Binding sitei118SubstrateBy similarity1
    Sitei125Critical for catalysisBy similarity1
    Sitei171Critical for catalysisBy similarity1
    Metal bindingi204Magnesium or manganeseBy similarity1
    Binding sitei204SubstrateBy similarity1
    Metal bindingi228Magnesium or manganeseBy similarity1
    Metal bindingi232Magnesium or manganeseBy similarity1

    GO - Molecular functioni

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

    GO - Biological processi

    • lysine biosynthetic process via aminoadipic acid Source: UniProtKB
    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

    BRENDAi1.1.1.85. 2305.
    UniPathwayiUPA00033; UER00030.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Homoisocitrate dehydrogenase (EC:1.1.1.87)
    Short name:
    HICDH
    Gene namesi
    Name:hicd
    Synonyms:hdh, hicdh
    Ordered Locus Names:TT_C1012
    OrganismiThermus thermophilus (strain HB27 / ATCC BAA-163 / DSM 7039)
    Taxonomic identifieri262724 [NCBI]
    Taxonomic lineageiBacteriaDeinococcus-ThermusDeinococciThermalesThermaceaeThermus
    Proteomesi
    • UP000000592 Componenti: Chromosome

    Pathology & Biotechi

    Disruption phenotypei

    Does not grow on minimal medium. Requires alpha-aminoadipate or lysine for growth.1 Publication

    Mutagenesis

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Mutagenesisi57E → V: Confers enzyme activity with 3-isopropylmalate; when associated with I-72; M-85; A-86; T-208; Y-217; M-238 and M-310. 1 Publication1
    Mutagenesisi72S → I: Confers enzyme activity with 3-isopropylmalate; when associated with V-57; M-85; A-86; T-208; Y-217; M-238 and M-310. 1 Publication1
    Mutagenesisi78 – 86PGFFGAIRY → EGYSSPIVA: Reduces activity with homoisocitrate. Abolishes activity with isocitrate. No activity with 3-isopropylmalate. 9
    Mutagenesisi78 – 83PGFFGA → EGYSSP: Reduces activity with homoisocitrate. Reduces activity with isocitrate. No activity with 3-isopropylmalate. 6
    Mutagenesisi80 – 83FFGA → YSSP: Strongly reduces activity with homoisocitrate. Reduces activity with isocitrate. No activity with 3-isopropylmalate. 4
    Mutagenesisi85R → M: Confers enzyme activity with 3-isopropylmalate; when associated with V-57; I-72; A-86; T-208; Y-217; M-238 and M-310. 2 Publications1
    Mutagenesisi85R → V: Confers low enzyme activity with 3-isopropylmalate. Reduces activity with homoisocitrate. Abolishes activity with isocitrate. 2 Publications1
    Mutagenesisi86Y → A: Confers enzyme activity with 3-isopropylmalate; when associated with V-57; I-72; M-85; T-208; Y-217; M-238 and M-310. 1 Publication1
    Mutagenesisi125Y → A: Reduces catalytic efficiency with isocitrate. 1 Publication1
    Mutagenesisi135V → M: Formation of homodimers instead of homotetramers. Increased affinity for isocitrate. Reduces enzyme activity with isocitrate. 1 Publication1
    Mutagenesisi208M → T: Confers enzyme activity with 3-isopropylmalate; when associated with V-57; I-72; M-85; A-86; T-208; Y-217; M-238 and M-310. 1 Publication1
    Mutagenesisi217F → Y: Confers enzyme activity with 3-isopropylmalate; when associated with V-57; I-72; M-85; A-86; T-208; M-238 and M-310. 1 Publication1
    Mutagenesisi238V → M: Confers enzyme activity with 3-isopropylmalate; when associated with V-57; I-72; M-85; A-86; T-208; Y-217; and M-310. 1 Publication1
    Mutagenesisi310R → M: Confers enzyme activity with 3-isopropylmalate; when associated with V-57; I-72; M-85; A-86; T-208; Y-217; and M-238. 1 Publication1

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    ChainiPRO_00004223041 – 334Homoisocitrate dehydrogenaseAdd BLAST334

    Interactioni

    Subunit structurei

    Homotetramer. Dimer of dimers. The homotetramer can transiently dissociate into homodimers.2 Publications

    Protein-protein interaction databases

    STRINGi262724.TTC1012.

    Structurei

    Secondary structure

    1334
    Legend: HelixTurnBeta strandPDB Structure known for this area
    Show more details
    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Beta strandi3 – 11Combined sources9
    Helixi14 – 26Combined sources13
    Turni27 – 29Combined sources3
    Beta strandi32 – 37Combined sources6
    Helixi41 – 47Combined sources7
    Beta strandi48 – 51Combined sources4
    Helixi53 – 60Combined sources8
    Beta strandi62 – 69Combined sources8
    Beta strandi74 – 76Combined sources3
    Helixi83 – 90Combined sources8
    Beta strandi95 – 101Combined sources7
    Beta strandi113 – 119Combined sources7
    Helixi121 – 123Combined sources3
    Helixi124 – 126Combined sources3
    Beta strandi129 – 132Combined sources4
    Beta strandi135 – 143Combined sources9
    Helixi144 – 159Combined sources16
    Beta strandi165 – 170Combined sources6
    Turni172 – 174Combined sources3
    Helixi178 – 190Combined sources13
    Beta strandi196 – 202Combined sources7
    Helixi203 – 212Combined sources10
    Helixi214 – 216Combined sources3
    Beta strandi218 – 222Combined sources5
    Helixi224 – 237Combined sources14
    Turni241 – 243Combined sources3
    Beta strandi245 – 249Combined sources5
    Beta strandi254 – 260Combined sources7
    Helixi264 – 266Combined sources3
    Helixi275 – 288Combined sources14
    Helixi291 – 307Combined sources17
    Helixi312 – 314Combined sources3
    Helixi320 – 332Combined sources13

    3D structure databases

    Select the link destinations:
    PDBei
    RCSB PDBi
    PDBji
    Links Updated
    PDB entryMethodResolution (Å)ChainPositionsPDBsum
    1X0LX-ray1.85A/B2-334[»]
    3AH3X-ray2.40A/B/C/D1-334[»]
    4YB4X-ray2.50A/B/C/D1-334[»]
    ProteinModelPortaliQ72IW9.
    SMRiQ72IW9.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Sequence similaritiesi

    Phylogenomic databases

    eggNOGiENOG4105C0C. Bacteria.
    COG0473. LUCA.
    KOiK05824.
    OMAiVMMPEDG.

    Family and domain databases

    Gene3Di3.40.718.10. 1 hit.
    InterProiIPR001804. 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]

    Sequencei

    Sequence statusi: Complete.

    Q72IW9-1 [UniParc]FASTAAdd to basket

    « Hide

            10         20         30         40         50
    MAYRICLIEG DGIGHEVIPA ARRVLEATGL PLEFVEAEAG WETFERRGTS
    60 70 80 90 100
    VPEETVEKIL SCHATLFGAA TSPTRKVPGF FGAIRYLRRR LDLYANVRPA
    110 120 130 140 150
    KSRPVPGSRP GVDLVIVREN TEGLYVEQER RYLDVAIADA VISKKASERI
    160 170 180 190 200
    GRAALRIAEG RPRKTLHIAH KANVLPLTQG LFLDTVKEVA KDFPLVNVQD
    210 220 230 240 250
    IIVDNCAMQL VMRPERFDVI VTTNLLGDIL SDLAAGLVGG LGLAPSGNIG
    260 270 280 290 300
    DTTAVFEPVH GSAPDIAGKG IANPTAAILS AAMMLDYLGE KEAAKRVEKA
    310 320 330
    VDLVLERGPR TPDLGGDATT EAFTEAVVEA LKSL
    Length:334
    Mass (Da):35,922
    Last modified:July 5, 2004 - v1
    Checksum:i82B018FED744FB49
    GO

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    AB075751 Genomic DNA. Translation: BAB88861.1.
    AE017221 Genomic DNA. Translation: AAS81354.1.
    RefSeqiWP_011173431.1. NC_005835.1.

    Genome annotation databases

    EnsemblBacteriaiAAS81354; AAS81354; TT_C1012.
    KEGGitth:TT_C1012.
    PATRICi23952429. VBITheThe54392_1005.

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    AB075751 Genomic DNA. Translation: BAB88861.1.
    AE017221 Genomic DNA. Translation: AAS81354.1.
    RefSeqiWP_011173431.1. NC_005835.1.

    3D structure databases

    Select the link destinations:
    PDBei
    RCSB PDBi
    PDBji
    Links Updated
    PDB entryMethodResolution (Å)ChainPositionsPDBsum
    1X0LX-ray1.85A/B2-334[»]
    3AH3X-ray2.40A/B/C/D1-334[»]
    4YB4X-ray2.50A/B/C/D1-334[»]
    ProteinModelPortaliQ72IW9.
    SMRiQ72IW9.
    ModBaseiSearch...
    MobiDBiSearch...

    Protein-protein interaction databases

    STRINGi262724.TTC1012.

    Protocols and materials databases

    Structural Biology KnowledgebaseSearch...

    Genome annotation databases

    EnsemblBacteriaiAAS81354; AAS81354; TT_C1012.
    KEGGitth:TT_C1012.
    PATRICi23952429. VBITheThe54392_1005.

    Phylogenomic databases

    eggNOGiENOG4105C0C. Bacteria.
    COG0473. LUCA.
    KOiK05824.
    OMAiVMMPEDG.

    Enzyme and pathway databases

    UniPathwayiUPA00033; UER00030.
    BRENDAi1.1.1.85. 2305.

    Family and domain databases

    Gene3Di3.40.718.10. 1 hit.
    InterProiIPR001804. 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]
    ProtoNetiSearch...

    Entry informationi

    Entry nameiHICDH_THET2
    AccessioniPrimary (citable) accession number: Q72IW9
    Secondary accession number(s): Q8RQU4
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: May 29, 2013
    Last sequence update: July 5, 2004
    Last modified: November 2, 2016
    This is version 79 of the entry and version 1 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programProkaryotic Protein Annotation Program

    Miscellaneousi

    Miscellaneous

    In vitro directed evolution leads to mutagenesis of key residues and increased activity with 3-isopropylmalate.

    Keywords - Technical termi

    3D-structure, Complete proteome

    Documents

    1. PATHWAY comments
      Index of metabolic and biosynthesis pathways
    2. PDB cross-references
      Index of Protein Data Bank (PDB) cross-references
    3. 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.