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P12269

- IMDH2_CRIGR

UniProt

P12269 - IMDH2_CRIGR

Protein

Inosine-5'-monophosphate dehydrogenase 2

Gene

IMPDH2

Organism
Cricetulus griseus (Chinese hamster) (Cricetulus barabensis griseus)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 119 (01 Oct 2014)
      Sequence version 1 (01 Oct 1989)
      Previous versions | rss
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    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. Could also have a single-stranded nucleic acid-binding activity and could play a role in RNA and/or DNA metabolism. It may also have a role in the development of malignancy and the growth progression of some tumors.UniRule annotation

    Catalytic activityi

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

    Cofactori

    Potassium.

    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

    Pathwayi

    Sites

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Binding sitei276 – 2761Inhibitor
    Metal bindingi326 – 3261Potassium; via carbonyl oxygenUniRule annotation
    Metal bindingi328 – 3281Potassium; via carbonyl oxygenUniRule annotation
    Binding sitei329 – 3291IMP
    Active sitei331 – 3311Thioimidate intermediate
    Metal bindingi331 – 3311Potassium; via carbonyl oxygenUniRule annotation
    Binding sitei333 – 3331Inhibitor
    Binding sitei441 – 4411IMP
    Metal bindingi500 – 5001Potassium; via carbonyl oxygen; shared with tetrameric partnerUniRule annotation
    Metal bindingi501 – 5011Potassium; via carbonyl oxygen; shared with tetrameric partnerUniRule annotation
    Metal bindingi502 – 5021Potassium; via carbonyl oxygen; shared with tetrameric partnerUniRule annotation

    Regions

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Nucleotide bindingi274 – 2763NADUniRule annotation
    Nucleotide bindingi324 – 3263NADUniRule annotation

    GO - Molecular functioni

    1. adenyl nucleotide binding Source: InterPro
    2. IMP dehydrogenase activity Source: UniProtKB-HAMAP
    3. metal ion binding Source: UniProtKB-HAMAP
    4. nucleotide binding Source: UniProtKB

    GO - Biological processi

    1. GMP biosynthetic process Source: UniProtKB-HAMAP

    Keywords - Molecular functioni

    Oxidoreductase

    Keywords - Biological processi

    GMP biosynthesis, Purine biosynthesis

    Keywords - Ligandi

    Metal-binding, NAD, Potassium

    Enzyme and pathway databases

    UniPathwayiUPA00601; UER00295.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Inosine-5'-monophosphate dehydrogenase 2UniRule annotation (EC:1.1.1.205UniRule annotation)
    Short name:
    IMP dehydrogenase 2UniRule annotation
    Short name:
    IMPD 2UniRule annotation
    Short name:
    IMPDH 2UniRule annotation
    Alternative name(s):
    IMPDH-II
    Gene namesi
    Name:IMPDH2UniRule annotation
    OrganismiCricetulus griseus (Chinese hamster) (Cricetulus barabensis griseus)
    Taxonomic identifieri10029 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaCricetidaeCricetinaeCricetulus
    ProteomesiUP000001075: Unassembled WGS sequence

    Subcellular locationi

    Cytoplasm UniRule annotation. Nucleus UniRule annotation

    GO - Cellular componenti

    1. cytoplasm Source: UniProtKB
    2. nucleus Source: UniProtKB

    Keywords - Cellular componenti

    Cytoplasm, Nucleus

    Pathology & Biotechi

    Mutagenesis

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Mutagenesisi275 – 2751S → A: No effect. 1 Publication
    Mutagenesisi276 – 2761S → A: Increases Ki for MPA 7-fold. 1 Publication
    Mutagenesisi329 – 3291S → A: Reduces activity by 87%. 1 Publication
    Mutagenesisi331 – 3311C → A: Loss of activity. 1 Publication
    Mutagenesisi333 – 3331T → I: Increases Ki for MPA 300-fold. 1 Publication
    Mutagenesisi364 – 3641D → A: Loss of activity. 1 Publication
    Mutagenesisi368 – 3681Q → A: No effect. 1 Publication
    Mutagenesisi441 – 4411Q → A: Reduces activity by over 95% and increases Ki for MPA 25-fold. 1 Publication

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Initiator methioninei1 – 11RemovedUniRule annotation
    Chaini2 – 514513Inosine-5'-monophosphate dehydrogenase 2PRO_0000093672Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Modified residuei122 – 1221PhosphoserineBy similarity
    Modified residuei400 – 4001PhosphotyrosineBy similarity
    Modified residuei416 – 4161PhosphoserineBy similarity
    Modified residuei511 – 5111N6-acetyllysineBy similarity

    Keywords - PTMi

    Acetylation, Phosphoprotein

    Proteomic databases

    PRIDEiP12269.

    Interactioni

    Subunit structurei

    Homotetramer.1 PublicationUniRule annotation

    Structurei

    Secondary structure

    1
    514
    Legend: HelixTurnBeta strand
    Show more details
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Helixi20 – 234
    Helixi32 – 343
    Beta strandi35 – 373
    Helixi46 – 483
    Beta strandi53 – 586
    Beta strandi60 – 634
    Beta strandi65 – 673
    Turni71 – 733
    Helixi76 – 8510
    Beta strandi88 – 914
    Helixi97 – 10812
    Beta strandi113 – 1153
    Helixi194 – 2007
    Beta strandi210 – 2134
    Turni214 – 2163
    Beta strandi217 – 2226
    Helixi224 – 2329
    Beta strandi247 – 2504
    Helixi255 – 26612
    Beta strandi270 – 2734
    Helixi281 – 29313
    Beta strandi298 – 3047
    Helixi307 – 31610
    Beta strandi319 – 3235
    Helixi333 – 3375
    Helixi343 – 35412
    Helixi355 – 3573
    Beta strandi361 – 3655
    Helixi370 – 3789
    Beta strandi382 – 3876
    Turni388 – 3925
    Beta strandi396 – 3983
    Beta strandi401 – 4055
    Beta strandi407 – 4126
    Turni417 – 4193
    Beta strandi444 – 4485
    Helixi453 – 47018
    Helixi476 – 48510
    Beta strandi490 – 4923
    Helixi495 – 5017

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    EntryMethodResolution (Å)ChainPositionsPDBsum
    1JR1X-ray2.60A/B1-514[»]
    ProteinModelPortaliP12269.
    SMRiP12269. Positions 10-514.
    ModBaseiSearch...
    MobiDBiSearch...

    Miscellaneous databases

    EvolutionaryTraceiP12269.

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Domaini114 – 17360CBS 1UniRule annotationAdd
    BLAST
    Domaini179 – 23759CBS 2UniRule annotationAdd
    BLAST

    Region

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Regioni364 – 3663IMP binding
    Regioni387 – 3882IMP binding
    Regioni411 – 4155IMP binding

    Sequence similaritiesi

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

    Keywords - Domaini

    CBS domain, Repeat

    Phylogenomic databases

    HOVERGENiHBG052122.
    KOiK00088.

    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]
    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.

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

    P12269-1 [UniParc]FASTAAdd to Basket

    « Hide

    MADYLISGGT SYVPDDGLTA QQLFNCGDGL TYNDFLILPG YIDFTADQVD    50
    LTSALTKKIT LKTPLVSSPM DTVTEAGMAI AMALTGGIGF IHHNCTPEFQ 100
    ANEVRKVKKY EQGFITDPVV LSPKDRVRDV FEAKARHGFC GIPITDTGRM 150
    GSRLVGIISS RDIDFLKEEE HDRFLEEIMT KREDLVVAPA GITLKEANEI 200
    LQRSKKGKLP IVNENDELVA IIARTDLKKN RDYPLASKDA KKQLLCGAAI 250
    GTHEDDKYRL DLLALAGVDV VVLDSSQGNS IFQINMIKYM KEKYPNLQVI 300
    GGNVVTAAQA KNLIDAGVDA LRVGMGCGSI CITQEVLACG RPQATAVYKV 350
    SEYARRFGVP VIADGGIQNV GHIAKALALG ASTVMMGSLL AATTEAPGEY 400
    FFSDGIRLKK YRGMGSLDAM DKHLSSQNRY FSEADKIKVA QGVSGAVQDK 450
    GSIHKFVPYL IAGIQHSCQD IGAKSLTQVR AMMYSGELKF EKRTSSAQVE 500
    GGVHSLHSYE KRLF 514
    Length:514
    Mass (Da):55,890
    Last modified:October 1, 1989 - v1
    Checksum:i5FA0138FA41E8A02
    GO

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    J04209 mRNA. Translation: AAA36993.1.
    JH001800 Genomic DNA. Translation: EGW10487.1.
    RefSeqiNP_001233751.1. NM_001246822.1.

    Genome annotation databases

    GeneIDi100689398.
    KEGGicge:100689398.

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    J04209 mRNA. Translation: AAA36993.1 .
    JH001800 Genomic DNA. Translation: EGW10487.1 .
    RefSeqi NP_001233751.1. NM_001246822.1.

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    Entry Method Resolution (Å) Chain Positions PDBsum
    1JR1 X-ray 2.60 A/B 1-514 [» ]
    ProteinModelPortali P12269.
    SMRi P12269. Positions 10-514.
    ModBasei Search...
    MobiDBi Search...

    Chemistry

    DrugBanki DB01024. Mycophenolic acid.

    Proteomic databases

    PRIDEi P12269.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    GeneIDi 100689398.
    KEGGi cge:100689398.

    Organism-specific databases

    CTDi 3615.

    Phylogenomic databases

    HOVERGENi HBG052122.
    KOi K00088.

    Enzyme and pathway databases

    UniPathwayi UPA00601 ; UER00295 .

    Miscellaneous databases

    EvolutionaryTracei P12269.

    Family and domain databases

    Gene3Di 3.20.20.70. 1 hit.
    HAMAPi MF_01964. IMPDH.
    InterProi IPR013785. Aldolase_TIM.
    IPR000644. CBS_dom.
    IPR005990. IMP_DH.
    IPR015875. IMP_DH/GMP_Rdtase_CS.
    IPR001093. IMP_DH_GMPRt.
    [Graphical view ]
    Pfami PF00571. CBS. 2 hits.
    PF00478. IMPDH. 1 hit.
    [Graphical view ]
    PIRSFi PIRSF000130. IMPDH. 1 hit.
    SMARTi SM00116. CBS. 2 hits.
    [Graphical view ]
    TIGRFAMsi TIGR01302. IMP_dehydrog. 1 hit.
    PROSITEi PS51371. CBS. 2 hits.
    PS00487. IMP_DH_GMP_RED. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    1. "Cloning and sequence analysis of the human and Chinese hamster inosine-5'-monophosphate dehydrogenase cDNAs."
      Collart F.R., Huberman E.
      J. Biol. Chem. 263:15769-15772(1988) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA], PROTEIN SEQUENCE OF 336-370.
    2. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    3. "Structure and mechanism of inosine monophosphate dehydrogenase in complex with the immunosuppressant mycophenolic acid."
      Sintchak M.D., Fleming M.A., Futer O., Raybuck S.A., Chambers S.P., Caron P.R., Murcko M.A., Wilson K.P.
      Cell 85:921-930(1996) [PubMed] [Europe PMC] [Abstract]
      Cited for: X-RAY CRYSTALLOGRAPHY (2.6 ANGSTROMS) IN COMPLEX WITH SUBSTRATE AND THE INHIBITOR MYCOPHENOLIC ACID (MPA), MUTAGENESIS OF SER-275; SER-276; SER-329; CYS-331; THR-333; ASP-364; GLN-368 AND GLN-441.

    Entry informationi

    Entry nameiIMDH2_CRIGR
    AccessioniPrimary (citable) accession number: P12269
    Secondary accession number(s): G3IB73
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: October 1, 1989
    Last sequence update: October 1, 1989
    Last modified: October 1, 2014
    This is version 119 of the entry and version 1 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program

    Miscellaneousi

    Keywords - Technical termi

    3D-structure, Complete proteome, Direct protein sequencing, Reference 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

    External Data

    Dasty 3