Human Gene IMPDH1 (ENST00000338791.11) from GENCODE V44
Description: Homo sapiens inosine monophosphate dehydrogenase 1 (IMPDH1), transcript variant 1, mRNA. (from RefSeq NM_000883) RefSeq Summary (NM_000883): The protein encoded by this gene acts as a homotetramer to regulate cell growth. The encoded protein is an enzyme that catalyzes the synthesis of xanthine monophosphate (XMP) from inosine-5'-monophosphate (IMP). This is the rate-limiting step in the de novo synthesis of guanine nucleotides. Defects in this gene are a cause of retinitis pigmentosa type 10 (RP10). Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Dec 2008]. Gencode Transcript: ENST00000338791.11 Gencode Gene: ENSG00000106348.19 Transcript (Including UTRs) Position: hg38 chr7:128,392,277-128,409,982 Size: 17,706 Total Exon Count: 17 Strand: - Coding Region Position: hg38 chr7:128,393,007-128,409,901 Size: 16,895 Coding Exon Count: 17
ID:IMDH1_HUMAN DESCRIPTION: RecName: Full=Inosine-5'-monophosphate dehydrogenase 1; Short=IMP dehydrogenase 1; Short=IMPD 1; Short=IMPDH 1; EC=1.1.1.205; AltName: Full=IMPDH-I; 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 (By similarity). 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=18 uM for Inosine 5'-phosphate; KM=46 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: Constitutively expressed. DISEASE: Defects in IMPDH1 are the cause of retinitis pigmentosa type 10 (RP10) [MIM:180105]. RP leads to degeneration of retinal photoreceptor cells. Patients typically have night vision blindness and loss of midperipheral visual field. As their condition progresses, they lose their far peripheral visual field and eventually central vision as well. RP10 inheritance is autosomal dominant. DISEASE: Defects in IMPDH1 are the cause of Leber congenital amaurosis type 11 (LCA11) [MIM:613837]. LCA11 is a severe dystrophy of the retina, typically becoming evident in the first years of life. Visual function is usually poor and often accompanied by nystagmus, sluggish or near-absent pupillary responses, photophobia, high hyperopia and keratoconus. 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. WEB RESOURCE: Name=Mutations of the IMPDH1 gene; Note=Retina International's Scientific Newsletter; URL="http://www.retina-international.org/files/sci-news/impdhmut.htm"; WEB RESOURCE: Name=GeneReviews; URL="http://www.ncbi.nlm.nih.gov/sites/GeneTests/lab/gene/IMPDH1";
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 P20839
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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
