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Protein

Inosine-5'-monophosphate dehydrogenase 3

Gene

IMD3

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 conversion of inosine 5'-phosphate (IMP) to xanthosine 5'-phosphate (XMP), the first committed and rate-limiting step in the de novo synthesis of guanine nucleotides, and therefore plays an important role in the regulation of cell growth.UniRule annotation3 Publications

Catalytic activityi

Inosine 5'-phosphate + NAD+ + H2O = xanthosine 5'-phosphate + NADH.UniRule annotation

Cofactori

K(+)UniRule annotation

Enzyme regulationi

Mycophenolic acid (MPA) is a non-competitive inhibitor that prevents formation of the closed enzyme conformation by binding to the same site as the amobile flap. In contrast, mizoribine monophosphate (MZP) is a competitive inhibitor that induces the closed conformation. MPA is a potent inhibitor of mammalian IMPDHs but a poor inhibitor of the bacterial enzymes. MZP is a more potent inhibitor of bacterial IMPDH.UniRule annotation

Kineticsi

  1. KM=100 µM for Inosine 5'-phosphate1 Publication
  2. KM=314 µM for NAD+1 Publication

    Pathway:iXMP biosynthesis via de novo pathway

    This protein is involved in step 1 of the subpathway that synthesizes XMP from IMP.UniRule annotation
    Proteins known to be involved in this subpathway in this organism are:
    1. Inosine-5'-monophosphate dehydrogenase 2 (IMD2), Inosine-5'-monophosphate dehydrogenase 3 (IMD3), Inosine-5'-monophosphate dehydrogenase 4 (IMD4), Putative inosine-5'-monophosphate dehydrogenase 1 (IMD1)
    This subpathway is part of the pathway XMP biosynthesis via de novo pathway, which is itself part of Purine metabolism.
    View all proteins of this organism that are known to be involved in the subpathway that synthesizes XMP from IMP, the pathway XMP biosynthesis via de novo pathway and in Purine metabolism.

    Sites

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Metal bindingi330 – 3301Potassium; via carbonyl oxygenUniRule annotation
    Metal bindingi332 – 3321Potassium; via carbonyl oxygenUniRule annotation
    Binding sitei333 – 3331IMPUniRule annotation
    Active sitei335 – 3351Thioimidate intermediateUniRule annotation
    Metal bindingi335 – 3351Potassium; via carbonyl oxygenUniRule annotation
    Binding sitei449 – 4491IMPUniRule annotation
    Metal bindingi508 – 5081Potassium; via carbonyl oxygen; shared with tetrameric partnerUniRule annotation
    Metal bindingi509 – 5091Potassium; via carbonyl oxygen; shared with tetrameric partnerUniRule annotation
    Metal bindingi510 – 5101Potassium; via carbonyl oxygen; shared with tetrameric partnerUniRule annotation

    Regions

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Nucleotide bindingi278 – 2803NADUniRule annotation
    Nucleotide bindingi328 – 3303NADUniRule annotation

    GO - Molecular functioni

    • IMP dehydrogenase activity Source: SGD
    • metal ion binding Source: UniProtKB-HAMAP
    • nucleotide binding Source: UniProtKB-HAMAP

    GO - Biological processi

    • GMP biosynthetic process Source: UniProtKB-HAMAP
    • GTP biosynthetic process Source: SGD
    Complete GO annotation...

    Keywords - Molecular functioni

    Oxidoreductase

    Keywords - Biological processi

    GMP biosynthesis, Purine biosynthesis

    Keywords - Ligandi

    Metal-binding, NAD, Potassium

    Enzyme and pathway databases

    BioCyciYEAST:YLR432W-MONOMER.
    ReactomeiREACT_301060. Purine ribonucleoside monophosphate biosynthesis.
    SABIO-RKP50095.
    UniPathwayiUPA00601; UER00295.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Inosine-5'-monophosphate dehydrogenase 3UniRule annotation (EC:1.1.1.205UniRule annotation)
    Short name:
    IMP dehydrogenase 3UniRule annotation
    Short name:
    IMPD 3UniRule annotation
    Short name:
    IMPDH 3UniRule annotation
    Gene namesi
    Name:IMD3UniRule annotation
    Ordered Locus Names:YLR432W
    ORF Names:L9753.4
    OrganismiSaccharomyces cerevisiae (strain ATCC 204508 / S288c) (Baker's yeast)
    Taxonomic identifieri559292 [NCBI]
    Taxonomic lineageiEukaryotaFungiDikaryaAscomycotaSaccharomycotinaSaccharomycetesSaccharomycetalesSaccharomycetaceaeSaccharomyces
    ProteomesiUP000002311 Componenti: Chromosome XII

    Organism-specific databases

    CYGDiYLR432w.
    EuPathDBiFungiDB:YLR432W.
    SGDiS000004424. IMD3.

    Subcellular locationi

    GO - Cellular componenti

    • cytoplasm Source: SGD
    Complete GO annotation...

    Keywords - Cellular componenti

    Cytoplasm

    Pathology & Biotechi

    Mutagenesis

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Mutagenesisi253 – 2531A → S: Increases drug-resistance to MPA. 1 Publication

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 523523Inosine-5'-monophosphate dehydrogenase 3PRO_0000093683Add
    BLAST

    Proteomic databases

    MaxQBiP50095.
    PaxDbiP50095.
    PeptideAtlasiP50095.

    Interactioni

    Subunit structurei

    Homotetramer. Seems to be able to form heterotetramers composed from more than 1 of the 3 IMPDH gene products (IMD2-4).UniRule annotation1 Publication

    Binary interactionsi

    WithEntry#Exp.IntActNotes
    IMD4P500946EBI-9190,EBI-9195

    Protein-protein interaction databases

    BioGridi31691. 129 interactions.
    DIPiDIP-1947N.
    IntActiP50095. 192 interactions.
    MINTiMINT-385605.

    Structurei

    3D structure databases

    ProteinModelPortaliP50095.
    SMRiP50095. Positions 10-521.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Domaini121 – 18363CBS 1UniRule annotationAdd
    BLAST
    Domaini184 – 24057CBS 2UniRule annotationAdd
    BLAST

    Region

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Regioni368 – 3703IMP bindingUniRule annotation
    Regioni391 – 3922IMP bindingUniRule annotation
    Regioni415 – 4195IMP bindingUniRule annotation

    Sequence similaritiesi

    Belongs to the IMPDH/GMPR family.UniRule annotation
    Contains 2 CBS domains.UniRule annotation

    Keywords - Domaini

    CBS domain, Repeat

    Phylogenomic databases

    eggNOGiCOG0517.
    GeneTreeiENSGT00530000062923.
    HOGENOMiHOG000165752.
    KOiK00088.
    OMAiGAYELNE.
    OrthoDBiEOG793BHK.

    Family and domain databases

    Gene3Di3.20.20.70. 1 hit.
    HAMAPiMF_01964. IMPDH.
    InterProiIPR013785. Aldolase_TIM.
    IPR000644. CBS_dom.
    IPR005990. IMP_DH.
    IPR015875. IMP_DH/GMP_Rdtase_CS.
    IPR001093. IMP_DH_GMPRt.
    [Graphical view]
    PANTHERiPTHR11911:SF6. PTHR11911:SF6. 1 hit.
    PfamiPF00571. CBS. 2 hits.
    PF00478. IMPDH. 1 hit.
    [Graphical view]
    PIRSFiPIRSF000130. IMPDH. 1 hit.
    SMARTiSM00116. CBS. 2 hits.
    [Graphical view]
    TIGRFAMsiTIGR01302. IMP_dehydrog. 1 hit.
    PROSITEiPS51371. CBS. 2 hits.
    PS00487. IMP_DH_GMP_RED. 1 hit.
    [Graphical view]

    Sequencei

    Sequence statusi: Complete.

    P50095-1 [UniParc]FASTAAdd to basket

    « Hide

            10         20         30         40         50
    MAAVRDYKTA LEFAKSLPRL DGLSVQELMD SKTRGGLTYN DFLVLPGLVD
    60 70 80 90 100
    FPSSEVSLQT KLTRNITLNT PFVSSPMDTV TESEMAIFMA LLGGIGFIHH
    110 120 130 140 150
    NCTPEDQADM VRRVKNYENG FINNPIVISP TTTVGEAKSM KERFGFSGFP
    160 170 180 190 200
    VTEDGKRNGK LMGIVTSRDI QFVEDNSLLV QDVMTKNPVT GAQGITLSEG
    210 220 230 240 250
    NEILKKIKKG KLLIVDDNGN LVSMLSRTDL MKNQNYPLAS KSATTKQLLC
    260 270 280 290 300
    GAAIGTIDAD KERLRLLVEA GLDVVILDSS QGNSIFQLNM IKWIKETFPD
    310 320 330 340 350
    LEIIAGNVAT REQAANLIAA GADGLRIGMG SGSICITQEV MACGRPQGTA
    360 370 380 390 400
    VYNVCEFANQ FGIPCMADGG VQNIGHITKA LALGSSTVMM GGMLAGTTES
    410 420 430 440 450
    PGEYFYQDGK RLKAYRGMGS IDAMQKTGTK GNASTSRYFS ESDSVLVAQG
    460 470 480 490 500
    VSGAVVDKGS IKKFIPYLYN GLQHSCQDIG YKSLTLLKEN VQSGKVRFEF
    510 520
    RTASAQLEGG VHNLHSYEKR LHN
    Length:523
    Mass (Da):56,585
    Last modified:October 1, 1996 - v1
    Checksum:iA0C84C22527AAEA6
    GO

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    U21094 Genomic DNA. Translation: AAB67516.1.
    BK006945 Genomic DNA. Translation: DAA09733.1.
    PIRiS59402.
    RefSeqiNP_013536.3. NM_001182320.3.

    Genome annotation databases

    EnsemblFungiiYLR432W; YLR432W; YLR432W.
    GeneIDi851152.
    KEGGisce:YLR432W.

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    U21094 Genomic DNA. Translation: AAB67516.1.
    BK006945 Genomic DNA. Translation: DAA09733.1.
    PIRiS59402.
    RefSeqiNP_013536.3. NM_001182320.3.

    3D structure databases

    ProteinModelPortaliP50095.
    SMRiP50095. Positions 10-521.
    ModBaseiSearch...
    MobiDBiSearch...

    Protein-protein interaction databases

    BioGridi31691. 129 interactions.
    DIPiDIP-1947N.
    IntActiP50095. 192 interactions.
    MINTiMINT-385605.

    Proteomic databases

    MaxQBiP50095.
    PaxDbiP50095.
    PeptideAtlasiP50095.

    Protocols and materials databases

    Structural Biology KnowledgebaseSearch...

    Genome annotation databases

    EnsemblFungiiYLR432W; YLR432W; YLR432W.
    GeneIDi851152.
    KEGGisce:YLR432W.

    Organism-specific databases

    CYGDiYLR432w.
    EuPathDBiFungiDB:YLR432W.
    SGDiS000004424. IMD3.

    Phylogenomic databases

    eggNOGiCOG0517.
    GeneTreeiENSGT00530000062923.
    HOGENOMiHOG000165752.
    KOiK00088.
    OMAiGAYELNE.
    OrthoDBiEOG793BHK.

    Enzyme and pathway databases

    UniPathwayiUPA00601; UER00295.
    BioCyciYEAST:YLR432W-MONOMER.
    ReactomeiREACT_301060. Purine ribonucleoside monophosphate biosynthesis.
    SABIO-RKP50095.

    Miscellaneous databases

    NextBioi967930.
    PROiP50095.

    Family and domain databases

    Gene3Di3.20.20.70. 1 hit.
    HAMAPiMF_01964. IMPDH.
    InterProiIPR013785. Aldolase_TIM.
    IPR000644. CBS_dom.
    IPR005990. IMP_DH.
    IPR015875. IMP_DH/GMP_Rdtase_CS.
    IPR001093. IMP_DH_GMPRt.
    [Graphical view]
    PANTHERiPTHR11911:SF6. PTHR11911:SF6. 1 hit.
    PfamiPF00571. CBS. 2 hits.
    PF00478. IMPDH. 1 hit.
    [Graphical view]
    PIRSFiPIRSF000130. IMPDH. 1 hit.
    SMARTiSM00116. CBS. 2 hits.
    [Graphical view]
    TIGRFAMsiTIGR01302. IMP_dehydrog. 1 hit.
    PROSITEiPS51371. CBS. 2 hits.
    PS00487. IMP_DH_GMP_RED. 1 hit.
    [Graphical view]
    ProtoNetiSearch...

    Publicationsi

    « Hide 'large scale' publications
    1. "The nucleotide sequence of Saccharomyces cerevisiae chromosome XII."
      Johnston M., Hillier L.W., Riles L., Albermann K., Andre B., Ansorge W., Benes V., Brueckner M., Delius H., Dubois E., Duesterhoeft A., Entian K.-D., Floeth M., Goffeau A., Hebling U., Heumann K., Heuss-Neitzel D., Hilbert H.
      , Hilger F., Kleine K., Koetter P., Louis E.J., Messenguy F., Mewes H.-W., Miosga T., Moestl D., Mueller-Auer S., Nentwich U., Obermaier B., Piravandi E., Pohl T.M., Portetelle D., Purnelle B., Rechmann S., Rieger M., Rinke M., Rose M., Scharfe M., Scherens B., Scholler P., Schwager C., Schwarz S., Underwood A.P., Urrestarazu L.A., Vandenbol M., Verhasselt P., Vierendeels F., Voet M., Volckaert G., Voss H., Wambutt R., Wedler E., Wedler H., Zimmermann F.K., Zollner A., Hani J., Hoheisel J.D.
      Nature 387:87-90(1997) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
      Strain: ATCC 204508 / S288c.
    2. Cited for: GENOME REANNOTATION.
      Strain: ATCC 204508 / S288c.
    3. Cited for: SUBCELLULAR LOCATION [LARGE SCALE ANALYSIS].
    4. Cited for: LEVEL OF PROTEIN EXPRESSION [LARGE SCALE ANALYSIS].
    5. "Functional distinctions between IMP dehydrogenase genes in providing mycophenolate resistance and guanine prototrophy to yeast."
      Hyle J.W., Shaw R.J., Reines D.
      J. Biol. Chem. 278:28470-28478(2003) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION.
    6. "Detection of the mycophenolate-inhibited form of IMP dehydrogenase in vivo."
      McPhillips C.C., Hyle J.W., Reines D.
      Proc. Natl. Acad. Sci. U.S.A. 101:12171-12176(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, SUBUNIT, BIOPHYSICOCHEMICAL PROPERTIES.
    7. "Dissection of the molecular basis of mycophenolate resistance in Saccharomyces cerevisiae."
      Jenks M.H., Reines D.
      Yeast 22:1181-1190(2005) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, MUTAGENESIS OF ALA-253.

    Entry informationi

    Entry nameiIMDH3_YEAST
    AccessioniPrimary (citable) accession number: P50095
    Secondary accession number(s): D6VZ67
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: October 1, 1996
    Last sequence update: October 1, 1996
    Last modified: July 22, 2015
    This is version 148 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 26300 molecules/cell in log phase SD medium.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 XII
      Yeast (Saccharomyces cerevisiae) chromosome XII: 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.