ID:IMDH2_HUMAN DESCRIPTION: RecName: Full=Inosine-5'-monophosphate dehydrogenase 2; Short=IMP dehydrogenase 2; Short=IMPD 2; Short=IMPDH 2; EC=1.1.1.205; AltName: Full=IMPDH-II; FUNCTION: 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 ACTIVITY: Inosine 5'-phosphate + NAD(+) + H(2)O = xanthosine 5'-phosphate + NADH. COFACTOR: Potassium. ENZYME REGULATION: 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. BIOPHYSICOCHEMICAL PROPERTIES: Kinetic parameters: KM=9.3 uM for Inosine 5'-phosphate; KM=32 uM for NAD(+); PATHWAY: Purine metabolism; XMP biosynthesis via de novo pathway; XMP from IMP: step 1/1. SUBUNIT: Homotetramer. SUBCELLULAR LOCATION: Cytoplasm. Nucleus. TISSUE SPECIFICITY: IMP type I is the main species in normal leukocytes and type II predominates over type I in the tumor. INDUCTION: Selectively up-regulated in neoplastic and replicating cells. PTM: The N-terminus is blocked. 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. SIMILARITY: Belongs to the IMPDH/GMPR family. SIMILARITY: Contains 2 CBS domains.
The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.
ModBase Predicted Comparative 3D Structure on P12268
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Orthologous Genes in Other Species
Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
US Server
Sequence and Links to Tools and Databases 
Common Gene Haplotype Alleles 
