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Protein

Inosine-5'-monophosphate dehydrogenase

Gene

GUA1

Organism
Pneumocystis carinii
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 annotation2 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. MPA is a potent inhibitor in culture.UniRule annotation1 Publication

Kineticsi

  1. KM=21.7 µM for Inosine 5'-phosphate1 Publication
  2. KM=314 µM for NAD+1 Publication

    Pathwayi

    Sites

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Metal bindingi333 – 3331Potassium; via carbonyl oxygenUniRule annotation
    Metal bindingi335 – 3351Potassium; via carbonyl oxygenUniRule annotation
    Binding sitei336 – 3361IMPUniRule annotation
    Active sitei338 – 3381Thioimidate intermediateUniRule annotation
    Metal bindingi338 – 3381Potassium; via carbonyl oxygenUniRule annotation
    Binding sitei455 – 4551IMPUniRule annotation
    Metal bindingi514 – 5141Potassium; via carbonyl oxygen; shared with tetrameric partnerUniRule annotation
    Metal bindingi515 – 5151Potassium; via carbonyl oxygen; shared with tetrameric partnerUniRule annotation

    Regions

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Nucleotide bindingi281 – 2833NADUniRule annotation
    Nucleotide bindingi331 – 3333NADUniRule annotation

    GO - Molecular functioni

    GO - Biological processi

    Complete GO annotation...

    Keywords - Molecular functioni

    Oxidoreductase

    Keywords - Biological processi

    GMP biosynthesis, Purine biosynthesis

    Keywords - Ligandi

    Metal-binding, NAD, Potassium

    Enzyme and pathway databases

    BRENDAi1.1.1.205. 4924.
    UniPathwayiUPA00601; UER00295.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Inosine-5'-monophosphate dehydrogenaseUniRule annotation (EC:1.1.1.205UniRule annotation)
    Short name:
    IMP dehydrogenaseUniRule annotation
    Short name:
    IMPDUniRule annotation
    Short name:
    IMPDHUniRule annotation
    Gene namesi
    Name:GUA1
    OrganismiPneumocystis carinii
    Taxonomic identifieri4754 [NCBI]
    Taxonomic lineageiEukaryotaFungiDikaryaAscomycotaTaphrinomycotinaPneumocystidomycetesPneumocystidaceaePneumocystis

    Subcellular locationi

    • Cytoplasm UniRule annotation

    GO - Cellular componenti

    Complete GO annotation...

    Keywords - Cellular componenti

    Cytoplasm

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 529529Inosine-5'-monophosphate dehydrogenasePRO_0000093679Add
    BLAST

    Post-translational modificationi

    The N-terminus is blocked.

    Interactioni

    Subunit structurei

    Homotetramer.UniRule annotation

    Structurei

    3D structure databases

    ProteinModelPortaliQ12658.
    SMRiQ12658. Positions 39-121, 238-528.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Domaini124 – 18562CBS 1UniRule annotationAdd
    BLAST
    Domaini187 – 24357CBS 2UniRule annotationAdd
    BLAST

    Region

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Regioni371 – 3733IMP bindingUniRule annotation
    Regioni394 – 3952IMP bindingUniRule annotation
    Regioni418 – 4225IMP bindingUniRule annotation

    Sequence similaritiesi

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

    Keywords - Domaini

    CBS domain, Repeat

    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]

    Sequences (2)i

    Sequence statusi: Complete.

    This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

    Isoform 1 (identifier: Q12658-1) [UniParc]FASTAAdd to basket

    This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

    « Hide

            10         20         30         40         50
    MGEDSYLCLS EEIKKKLEEY SEKDGYDLDS LICSRRHGGL TYNDIIILPG
    60 70 80 90 100
    YIDFEVNSVS LESHITKKIV LKTPFMSSPM DTVTESDMAI NLALLGGIGV
    110 120 130 140 150
    IHHNCTIEEQ TEMVRKVKKF ENGFITSPIV LSLNHRVRDV RRIKEELGFS
    160 170 180 190 200
    GIPITDTGQL NGKLLGIVTS RDIQFHNNDE SFLSEVMTKD LVTGSEGIRL
    210 220 230 240 250
    EEANEILRSC KKGKLPIVDK EGNLTALLSR SDLMKNLHFP LASKLPDSKQ
    260 270 280 290 300
    LICAAAVGTR PDDRIRLKHL VEAGLDIVVL DSSQGNSIYQ INMIKWIKKE
    310 320 330 340 350
    FPNLEVIAGN VVTREQAANL ISAGADALRV GMGSGSICIT QEIMAVGRPQ
    360 370 380 390 400
    ATAVYAVSEF ASKFGVPTIA DGGIENIGHI TKALALGASA VMMGNLLAGT
    410 420 430 440 450
    TESPGQYYYR DGQRLKSYRG MGSIDAMEHL SGKNKGDNAA SSRYFGEADT
    460 470 480 490 500
    IRVAQGVSGS VIDKGSLHVY VPYLRTGLQH SLQDIGVQNL TELRKQVKEK
    510 520
    NIRFEFRTVA SQLEGNVHGL DSYQKKLWS
    Length:529
    Mass (Da):58,066
    Last modified:February 22, 2012 - v2
    Checksum:i030573A8854ADB5A
    GO
    Isoform 2 (identifier: Q12658-2) [UniParc]FASTAAdd to basket

    The sequence of this isoform differs from the canonical sequence as follows:
         1-75: Missing.

    Show »
    Length:454
    Mass (Da):49,483
    Checksum:i4B6A5AF9B4451210
    GO

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti187 – 1871M → I in AAA97462 (PubMed:8980752).Curated
    Sequence conflicti255 – 2551A → Q in AAA97462 (PubMed:8980752).Curated
    Sequence conflicti297 – 2971I → N in AAA97462 (PubMed:8980752).Curated

    Alternative sequence

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Alternative sequencei1 – 7575Missing in isoform 2. 2 PublicationsVSP_042318Add
    BLAST

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    U42442 mRNA. Translation: AAA97462.1.
    AF196975 mRNA. Translation: AAF13230.1.

    Keywords - Coding sequence diversityi

    Alternative splicing

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    U42442 mRNA. Translation: AAA97462.1.
    AF196975 mRNA. Translation: AAF13230.1.

    3D structure databases

    ProteinModelPortaliQ12658.
    SMRiQ12658. Positions 39-121, 238-528.
    ModBaseiSearch...
    MobiDBiSearch...

    Protocols and materials databases

    Structural Biology KnowledgebaseSearch...

    Enzyme and pathway databases

    UniPathwayiUPA00601; UER00295.
    BRENDAi1.1.1.205. 4924.

    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

    1. "IMP dehydrogenase from Pneumocystis carinii as a potential drug target."
      O'Gara M.J., Lee C.H., Weinberg G.A., Nott J.M., Queener S.F.
      Antimicrob. Agents Chemother. 41:40-48(1997) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), PROTEIN SEQUENCE OF 119-132; 172-186 AND 300-313, FUNCTION, BIOPHYSICOCHEMICAL PROPERTIES, ENZYME REGULATION.
    2. "Differential splicing of Pneumocystis carinii f. sp. carinii inosine 5'-monophosphate dehydrogenase pre-mRNA."
      Ye D., Lee C.H., Queener S.F.
      Gene 263:151-158(2001) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2), FUNCTION.

    Entry informationi

    Entry nameiIMDH_PNECA
    AccessioniPrimary (citable) accession number: Q12658
    Secondary accession number(s): Q9UVL0
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: November 1, 1997
    Last sequence update: February 22, 2012
    Last modified: April 1, 2015
    This is version 90 of the entry and version 2 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programFungal Protein Annotation Program

    Miscellaneousi

    Keywords - Technical termi

    Direct protein sequencing

    Documents

    1. PATHWAY comments
      Index of metabolic and biosynthesis pathways
    2. SIMILARITY comments
      Index of protein domains and families

    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.