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Protein

Inosine-5'-monophosphate dehydrogenase 2

Gene

IMPDH2

Organism
Homo sapiens (Human)
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. 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.

Catalytic activityi

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

Cofactori

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. Subject to product inhibition by XMP and NADH. Also inhibited by ADP.UniRule annotation1 Publication

Kineticsi

  1. KM=9.3 µM for Inosine 5'-phosphate2 Publications
  2. KM=32 µM for NAD+2 Publications

    Pathway: XMP 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 (IMPDH), Inosine-5'-monophosphate dehydrogenase (IMPDH1), Inosine-5'-monophosphate dehydrogenase (IMPDH), Inosine-5'-monophosphate dehydrogenase (IMPDH), Inosine-5'-monophosphate dehydrogenase 1 (IMPDH1), Inosine-5'-monophosphate dehydrogenase 2 (IMPDH2), Inosine-5'-monophosphate dehydrogenase (IMPDH1), Inosine-5'-monophosphate dehydrogenase (DKFZp781N0678)
    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 bindingi326 – 3261Potassium; via carbonyl oxygenUniRule annotation1 Publication
    Metal bindingi328 – 3281Potassium; via carbonyl oxygenUniRule annotation1 Publication
    Binding sitei329 – 3291IMPUniRule annotation
    Active sitei331 – 3311Thioimidate intermediateUniRule annotation1 Publication
    Metal bindingi331 – 3311Potassium; via carbonyl oxygenUniRule annotation1 Publication
    Binding sitei441 – 4411IMPUniRule annotation
    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 – 2763NAD
    Nucleotide bindingi324 – 3263NADUniRule annotation

    GO - Molecular functioni

    • DNA binding Source: UniProtKB-KW
    • IMP dehydrogenase activity Source: ProtInc
    • metal ion binding Source: UniProtKB-HAMAP
    • nucleotide binding Source: UniProtKB
    • RNA binding Source: UniProtKB-KW

    GO - Biological processi

    Complete GO annotation...

    Keywords - Molecular functioni

    Oxidoreductase

    Keywords - Biological processi

    GMP biosynthesis, Purine biosynthesis

    Keywords - Ligandi

    DNA-binding, Metal-binding, NAD, Potassium, RNA-binding

    Enzyme and pathway databases

    BioCyciMetaCyc:HS11242-MONOMER.
    BRENDAi1.1.1.205. 2681.
    ReactomeiREACT_1776. Purine ribonucleoside monophosphate biosynthesis.
    SABIO-RKP12268.
    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
    Synonyms:IMPD2
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    ProteomesiUP000005640 Componenti: Chromosome 3

    Organism-specific databases

    HGNCiHGNC:6053. IMPDH2.

    Subcellular locationi

    GO - Cellular componenti

    • cytoplasm Source: UniProtKB
    • cytosol Source: Reactome
    • extracellular exosome Source: UniProtKB
    • membrane Source: UniProtKB
    • nucleus Source: UniProtKB
    • peroxisomal membrane Source: UniProtKB
    Complete GO annotation...

    Keywords - Cellular componenti

    Cytoplasm, Nucleus

    Pathology & Biotechi

    Organism-specific databases

    PharmGKBiPA29863.

    Chemistry

    DrugBankiDB01033. Mercaptopurine.
    DB00688. Mycophenolate mofetil.
    DB01024. Mycophenolic acid.

    Polymorphism and mutation databases

    BioMutaiIMPDH2.
    DMDMi124419.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Initiator methioninei1 – 11RemovedUniRule annotation1 Publication
    Chaini2 – 514513Inosine-5'-monophosphate dehydrogenase 2PRO_0000093673Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Modified residuei122 – 1221Phosphoserine2 Publications
    Modified residuei400 – 4001Phosphotyrosine1 Publication
    Modified residuei416 – 4161Phosphoserine2 Publications
    Modified residuei511 – 5111N6-acetyllysine1 Publication

    Post-translational modificationi

    The N-terminus is blocked.

    Keywords - PTMi

    Acetylation, Phosphoprotein

    Proteomic databases

    MaxQBiP12268.
    PaxDbiP12268.
    PeptideAtlasiP12268.
    PRIDEiP12268.

    2D gel databases

    REPRODUCTION-2DPAGEIPI00291510.
    P12268.
    UCD-2DPAGEP12268.

    PTM databases

    PhosphoSiteiP12268.

    Expressioni

    Tissue specificityi

    IMP type I is the main species in normal leukocytes and type II predominates over type I in the tumor.

    Inductioni

    Selectively up-regulated in neoplastic and replicating cells.

    Gene expression databases

    BgeeiP12268.
    CleanExiHS_IMPDH2.
    ExpressionAtlasiP12268. baseline and differential.
    GenevisibleiP12268. HS.

    Organism-specific databases

    HPAiCAB020717.
    HPA001400.

    Interactioni

    Subunit structurei

    Homotetramer.UniRule annotation3 Publications

    Binary interactionsi

    WithEntry#Exp.IntActNotes
    APIPQ96GX93EBI-353389,EBI-359248
    RSG1Q9BU203EBI-353389,EBI-750332

    Protein-protein interaction databases

    BioGridi109828. 47 interactions.
    IntActiP12268. 15 interactions.
    MINTiMINT-2860057.
    STRINGi9606.ENSP00000321584.

    Structurei

    Secondary structure

    1
    514
    Legend: HelixTurnBeta strand
    Show more details
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Beta strandi17 – 193Combined sources
    Helixi20 – 245Combined sources
    Beta strandi25 – 273Combined sources
    Helixi32 – 343Combined sources
    Beta strandi35 – 373Combined sources
    Helixi46 – 483Combined sources
    Beta strandi53 – 586Combined sources
    Beta strandi60 – 678Combined sources
    Turni71 – 733Combined sources
    Helixi77 – 859Combined sources
    Beta strandi89 – 913Combined sources
    Helixi97 – 10812Combined sources
    Turni109 – 1135Combined sources
    Beta strandi123 – 1253Combined sources
    Beta strandi142 – 1498Combined sources
    Beta strandi152 – 1587Combined sources
    Helixi161 – 1644Combined sources
    Turni175 – 1773Combined sources
    Beta strandi183 – 1853Combined sources
    Helixi194 – 20310Combined sources
    Beta strandi209 – 2124Combined sources
    Beta strandi214 – 2163Combined sources
    Beta strandi220 – 2223Combined sources
    Beta strandi247 – 2504Combined sources
    Helixi256 – 26510Combined sources
    Beta strandi270 – 2734Combined sources
    Helixi281 – 29313Combined sources
    Beta strandi295 – 30410Combined sources
    Helixi307 – 31610Combined sources
    Beta strandi319 – 3235Combined sources
    Beta strandi328 – 3314Combined sources
    Helixi333 – 3364Combined sources
    Helixi343 – 35412Combined sources
    Helixi355 – 3573Combined sources
    Beta strandi361 – 3655Combined sources
    Helixi370 – 3789Combined sources
    Beta strandi382 – 3876Combined sources
    Helixi388 – 3903Combined sources
    Beta strandi396 – 3983Combined sources
    Beta strandi404 – 4063Combined sources
    Beta strandi409 – 4124Combined sources
    Turni417 – 4193Combined sources
    Beta strandi444 – 4474Combined sources
    Helixi453 – 47119Combined sources
    Helixi476 – 4849Combined sources
    Beta strandi490 – 4923Combined sources
    Helixi495 – 5017Combined sources

    3D structure databases

    Select the link destinations:
    PDBei
    RCSB PDBi
    PDBji
    Links Updated
    EntryMethodResolution (Å)ChainPositionsPDBsum
    1B3OX-ray2.90A/B1-514[»]
    1NF7X-ray2.65A/B1-514[»]
    1NFBX-ray2.90A/B1-514[»]
    ProteinModelPortaliP12268.
    SMRiP12268. Positions 10-514.
    ModBaseiSearch...
    MobiDBiSearch...

    Miscellaneous databases

    EvolutionaryTraceiP12268.

    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 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.
    HOVERGENiHBG052122.
    KOiK00088.
    OMAiRVRDVFQ.
    PhylomeDBiP12268.
    TreeFamiTF300378.

    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.

    P12268-1 [UniParc]FASTAAdd to basket

    « Hide

            10         20         30         40         50
    MADYLISGGT SYVPDDGLTA QQLFNCGDGL TYNDFLILPG YIDFTADQVD
    60 70 80 90 100
    LTSALTKKIT LKTPLVSSPM DTVTEAGMAI AMALTGGIGF IHHNCTPEFQ
    110 120 130 140 150
    ANEVRKVKKY EQGFITDPVV LSPKDRVRDV FEAKARHGFC GIPITDTGRM
    160 170 180 190 200
    GSRLVGIISS RDIDFLKEEE HDCFLEEIMT KREDLVVAPA GITLKEANEI
    210 220 230 240 250
    LQRSKKGKLP IVNEDDELVA IIARTDLKKN RDYPLASKDA KKQLLCGAAI
    260 270 280 290 300
    GTHEDDKYRL DLLAQAGVDV VVLDSSQGNS IFQINMIKYI KDKYPNLQVI
    310 320 330 340 350
    GGNVVTAAQA KNLIDAGVDA LRVGMGSGSI CITQEVLACG RPQATAVYKV
    360 370 380 390 400
    SEYARRFGVP VIADGGIQNV GHIAKALALG ASTVMMGSLL AATTEAPGEY
    410 420 430 440 450
    FFSDGIRLKK YRGMGSLDAM DKHLSSQNRY FSEADKIKVA QGVSGAVQDK
    460 470 480 490 500
    GSIHKFVPYL IAGIQHSCQD IGAKSLTQVR AMMYSGELKF EKRTSSAQVE
    510
    GGVHSLHSYE KRLF
    Length:514
    Mass (Da):55,805
    Last modified:May 1, 1991 - v2
    Checksum:i876BEA0EC1DDBEE9
    GO

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti190 – 1912AG → RS in AAA36112 (PubMed:2902093).Curated

    Polymorphismi

    Genetic variants in the IMPDH2 gene may account for the large inter-individual variability in enzyme activity, immunosuppressive efficacy and side effects in transplant recipients receiving mycophenolic acid.

    Natural variant

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti263 – 2631L → F Found in transplant patients; functional polymorphism; results in 10-fold decrease of enzymatic activity. 1 Publication
    Corresponds to variant rs121434586 [ dbSNP | Ensembl ].
    VAR_070542

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    J04208 mRNA. Translation: AAA36112.1.
    L33842 Genomic DNA. Translation: AAA67054.1.
    L39210 Genomic DNA. Translation: AAB70699.1.
    BC006124 mRNA. Translation: AAH06124.1.
    BC012840 mRNA. Translation: AAH12840.1.
    BC015567 mRNA. Translation: AAH15567.1.
    L08114 Genomic DNA. Translation: AAA36113.1.
    CCDSiCCDS2786.1.
    PIRiI52303. A31997.
    RefSeqiNP_000875.2. NM_000884.2.
    UniGeneiHs.654400.

    Genome annotation databases

    EnsembliENST00000326739; ENSP00000321584; ENSG00000178035.
    GeneIDi3615.
    KEGGihsa:3615.
    UCSCiuc003cvt.3. human.

    Keywords - Coding sequence diversityi

    Polymorphism

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    J04208 mRNA. Translation: AAA36112.1.
    L33842 Genomic DNA. Translation: AAA67054.1.
    L39210 Genomic DNA. Translation: AAB70699.1.
    BC006124 mRNA. Translation: AAH06124.1.
    BC012840 mRNA. Translation: AAH12840.1.
    BC015567 mRNA. Translation: AAH15567.1.
    L08114 Genomic DNA. Translation: AAA36113.1.
    CCDSiCCDS2786.1.
    PIRiI52303. A31997.
    RefSeqiNP_000875.2. NM_000884.2.
    UniGeneiHs.654400.

    3D structure databases

    Select the link destinations:
    PDBei
    RCSB PDBi
    PDBji
    Links Updated
    EntryMethodResolution (Å)ChainPositionsPDBsum
    1B3OX-ray2.90A/B1-514[»]
    1NF7X-ray2.65A/B1-514[»]
    1NFBX-ray2.90A/B1-514[»]
    ProteinModelPortaliP12268.
    SMRiP12268. Positions 10-514.
    ModBaseiSearch...
    MobiDBiSearch...

    Protein-protein interaction databases

    BioGridi109828. 47 interactions.
    IntActiP12268. 15 interactions.
    MINTiMINT-2860057.
    STRINGi9606.ENSP00000321584.

    Chemistry

    BindingDBiP12268.
    ChEMBLiCHEMBL2002.
    DrugBankiDB01033. Mercaptopurine.
    DB00688. Mycophenolate mofetil.
    DB01024. Mycophenolic acid.
    GuidetoPHARMACOLOGYi2625.

    PTM databases

    PhosphoSiteiP12268.

    Polymorphism and mutation databases

    BioMutaiIMPDH2.
    DMDMi124419.

    2D gel databases

    REPRODUCTION-2DPAGEIPI00291510.
    P12268.
    UCD-2DPAGEP12268.

    Proteomic databases

    MaxQBiP12268.
    PaxDbiP12268.
    PeptideAtlasiP12268.
    PRIDEiP12268.

    Protocols and materials databases

    DNASUi3615.
    Structural Biology KnowledgebaseSearch...

    Genome annotation databases

    EnsembliENST00000326739; ENSP00000321584; ENSG00000178035.
    GeneIDi3615.
    KEGGihsa:3615.
    UCSCiuc003cvt.3. human.

    Organism-specific databases

    CTDi3615.
    GeneCardsiGC03M049061.
    HGNCiHGNC:6053. IMPDH2.
    HPAiCAB020717.
    HPA001400.
    MIMi146691. gene.
    neXtProtiNX_P12268.
    PharmGKBiPA29863.
    GenAtlasiSearch...

    Phylogenomic databases

    eggNOGiCOG0517.
    GeneTreeiENSGT00530000062923.
    HOGENOMiHOG000165752.
    HOVERGENiHBG052122.
    KOiK00088.
    OMAiRVRDVFQ.
    PhylomeDBiP12268.
    TreeFamiTF300378.

    Enzyme and pathway databases

    UniPathwayiUPA00601; UER00295.
    BioCyciMetaCyc:HS11242-MONOMER.
    BRENDAi1.1.1.205. 2681.
    ReactomeiREACT_1776. Purine ribonucleoside monophosphate biosynthesis.
    SABIO-RKP12268.

    Miscellaneous databases

    ChiTaRSiIMPDH2. human.
    EvolutionaryTraceiP12268.
    GeneWikiiIMPDH2.
    GenomeRNAii3615.
    NextBioi14143.
    PROiP12268.
    SOURCEiSearch...

    Gene expression databases

    BgeeiP12268.
    CleanExiHS_IMPDH2.
    ExpressionAtlasiP12268. baseline and differential.
    GenevisibleiP12268. HS.

    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]
    ProtoNetiSearch...

    Publicationsi

    « Hide 'large scale' publications
    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], PARTIAL PROTEIN SEQUENCE.
    2. "Two distinct cDNAs for human IMP dehydrogenase."
      Natsumeda Y., Ohno S., Kawasaki H., Konno Y., Weber G., Suzuki K.
      J. Biol. Chem. 265:5292-5295(1990) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA].
      Tissue: Spleen.
    3. "Cloning and sequence of the human type II IMP dehydrogenase gene."
      Glesne D.A., Huberman E.
      Biochem. Biophys. Res. Commun. 205:537-544(1994) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
      Tissue: Blood.
    4. "Characterization of the human inosine-5'-monophosphate dehydrogenase type II gene."
      Zimmermann A.G., Spychala J., Mitchell B.S.
      J. Biol. Chem. 270:6808-6814(1995) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
    5. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
      The MGC Project Team
      Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
      Tissue: B-cell, Colon and Placenta.
    6. "Chromosomal localization and structure of the human type II IMP dehydrogenase gene."
      Glesne D.A., Collart F.R., Varkony T., Drabkin H., Huberman E.
      Genomics 16:274-277(1993) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 461-514.
    7. "Characterization of human type I and type II IMP dehydrogenases."
      Carr S.F., Papp E., Wu J.C., Natsumeda Y.
      J. Biol. Chem. 268:27286-27290(1993) [PubMed] [Europe PMC] [Abstract]
      Cited for: PROTEIN SEQUENCE OF 2-11, BIOPHYSICOCHEMICAL PROPERTIES, SUBUNIT, ENZYME REGULATION.
    8. "Recombinant human inosine monophosphate dehydrogenase type I and type II proteins. Purification and characterization of inhibitor binding."
      Hager P.W., Collart F.R., Huberman E., Mitchell B.S.
      Biochem. Pharmacol. 49:1323-1329(1995) [PubMed] [Europe PMC] [Abstract]
      Cited for: PROTEIN SEQUENCE OF N-TERMINUS, BIOPHYSICOCHEMICAL PROPERTIES.
    9. "Inosine 5'-monophosphate dehydrogenase binds nucleic acids in vitro and in vivo."
      McLean J.E., Hamaguchi N., Belenky P., Mortimer S.E., Stanton M., Hedstrom L.
      Biochem. J. 379:243-251(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: SUBCELLULAR LOCATION, NUCLEIC ACID-BINDING.
    10. "Immunoaffinity profiling of tyrosine phosphorylation in cancer cells."
      Rush J., Moritz A., Lee K.A., Guo A., Goss V.L., Spek E.J., Zhang H., Zha X.-M., Polakiewicz R.D., Comb M.J.
      Nat. Biotechnol. 23:94-101(2005) [PubMed] [Europe PMC] [Abstract]
      Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-400, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    11. "Global, in vivo, and site-specific phosphorylation dynamics in signaling networks."
      Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M.
      Cell 127:635-648(2006) [PubMed] [Europe PMC] [Abstract]
      Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
      Tissue: Cervix carcinoma.
    12. "A novel variant L263F in human inosine 5'-monophosphate dehydrogenase 2 is associated with diminished enzyme activity."
      Wang J., Zeevi A., Webber S., Girnita D.M., Addonizio L., Selby R., Hutchinson I.V., Burckart G.J.
      Pharmacogenet. Genomics 17:283-290(2007) [PubMed] [Europe PMC] [Abstract]
      Cited for: POLYMORPHISM, VARIANT PHE-263.
    13. Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-122, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
      Tissue: Cervix carcinoma.
    14. "Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach."
      Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.
      Anal. Chem. 81:4493-4501(2009) [PubMed] [Europe PMC] [Abstract]
      Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    15. "Lysine acetylation targets protein complexes and co-regulates major cellular functions."
      Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T.C., Olsen J.V., Mann M.
      Science 325:834-840(2009) [PubMed] [Europe PMC] [Abstract]
      Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-511, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    16. "Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis."
      Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.
      Sci. Signal. 3:RA3-RA3(2010) [PubMed] [Europe PMC] [Abstract]
      Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-122 AND SER-416, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
      Tissue: Cervix carcinoma.
    17. Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    18. "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome."
      Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L., Ye M., Zou H.
      J. Proteomics 96:253-262(2014) [PubMed] [Europe PMC] [Abstract]
      Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-416, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
      Tissue: Liver.
    19. "Crystal structure of human type II inosine monophosphate dehydrogenase: implications for ligand binding and drug design."
      Colby T.D., Vanderveen K., Strickler M.D., Markham G.D., Goldstein B.M.
      Proc. Natl. Acad. Sci. U.S.A. 96:3531-3536(1999) [PubMed] [Europe PMC] [Abstract]
      Cited for: X-RAY CRYSTALLOGRAPHY (2.9 ANGSTROMS), ACTIVE SITE.
    20. "Crystal structure of human inosine monophosphate dehydrogenase type II complexed with the MPA/NAD analog C2-MAD."
      Risal D., Strickler M.D., Goldstein B.M.
      Submitted (DEC-2002) to the PDB data bank
      Cited for: X-RAY CRYSTALLOGRAPHY (2.65 ANGSTROMS) IN COMPLEX WITH INHIBITOR AND POTASSIUM.
    21. "The conformation of NAD bound to human inosine monophosphate Dehydrogenase Type II."
      Risal D., Strickler M.D., Goldstein B.M.
      Submitted (DEC-2002) to the PDB data bank
      Cited for: X-RAY CRYSTALLOGRAPHY (2.90 ANGSTROMS) IN COMPLEX WITH NAD(+).

    Entry informationi

    Entry nameiIMDH2_HUMAN
    AccessioniPrimary (citable) accession number: P12268
    Secondary accession number(s): Q6LEF3
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: October 1, 1989
    Last sequence update: May 1, 1991
    Last modified: June 24, 2015
    This is version 184 of the entry and version 2 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program
    DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

    Miscellaneousi

    Miscellaneous

    Because IMPDH activity is tightly linked with cell proliferation, it has been recognized as a target for cancer and viral chemotherapy and as a target for immunosuppressive drugs. The activities of the antitumor drug tiazofurin, the antiviral drug ribavirin, and the immunosuppressive drugs mizoribine and mycophenolic acid (MPA) are attributed to the inhibition of IMPDH. In addition, bacterial and parasitic IMPDH's differ significantly from mammalian enzymes, which makes it a suitable target for anti-infective drugs.

    Keywords - Technical termi

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

    Documents

    1. Human chromosome 3
      Human chromosome 3: entries, gene names and cross-references to MIM
    2. Human entries with polymorphisms or disease mutations
      List of human entries with polymorphisms or disease mutations
    3. Human polymorphisms and disease mutations
      Index of human polymorphisms and disease mutations
    4. MIM cross-references
      Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
    5. PATHWAY comments
      Index of metabolic and biosynthesis pathways
    6. PDB cross-references
      Index of Protein Data Bank (PDB) cross-references
    7. 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.