IMPDH2

IMPDH2
Available structures
PDB	Ortholog search: PDBe RCSB
List of PDB id codes
	1B3O, 1NF7, 1NFB
Identifiers
Aliases	IMPDH2 , IMPD2, IMPDH-II, IMP (inosine 5'-monophosphate) dehydrogenase 2, inosine monophosphate dehydrogenase 2
External IDs	OMIM: 146691 MGI: 109367 HomoloGene: 48919 GeneCards: IMPDH2
Gene location (Human)
Chr.	Chromosome 3 (human)
End	49,029,447 bp
Gene location (Mouse)
Chr.	Chromosome 9 (mouse)
End	108,442,783 bp
RNA expression pattern
	Top expressed in
	body of pancreas; ; right uterine tube; ; canal of the cervix; ; vulva; ; skin of abdomen; ; embryo; ; nipple; ; ganglionic eminence; ; gastrocnemius muscle; ; human penis;
	Top expressed in
	morula; ; uterus; ; spermatid; ; yolk sac; ; ovary; ; spleen; ; lip; ; ganglionic eminence; ; thymus; ; limb;
	More reference expression data
	n/a
Gene ontology
Molecular function	DNA binding ; metal ion binding ; catalytic activity ; protein binding ; RNA binding ; oxidoreductase activity ; nucleotide binding ; IMP dehydrogenase activity ;
Cellular component	cytoplasm ; membrane ; peroxisomal membrane ; extracellular exosome ; nucleus ; extracellular region ; cytosol ; secretory granule lumen ; ficolin-1-rich granule lumen ;
Biological process	cellular response to interleukin-4 ; purine nucleotide biosynthetic process ; retina development in camera-type eye ; purine ribonucleoside monophosphate biosynthetic process ; lymphocyte proliferation ; GMP biosynthetic process ; protein homotetramerization ; GTP biosynthetic process ; neutrophil degranulation ; circadian rhythm ;
	Sources:Amigo / QuickGO
Orthologs
	3615
	23918
	ENSG00000178035
	ENSMUSG00000062867
	P12268
	P24547
	NM_000884
	NM_011830 ; NM_001378921
	NP_000875
	NP_035960 ; NP_001365850
	Wikidata
View/Edit Human	View/Edit Mouse

Last updated February 24, 2024

Inosine-5'-monophosphate dehydrogenase 2, also known as IMP dehydrogenase 2, is an enzyme that in humans is encoded by the IMPDH2 gene.^[5]^[6]^[7]

Function

IMP dehydrogenase 2 is the rate-limiting enzyme in the de novo guanine nucleotide biosynthesis. It is thus involved in maintaining cellular guanine deoxy- and ribonucleotide pools needed for DNA and RNA synthesis. IMPDH2 catalyzes the NAD-dependent oxidation of inosine-5'-monophosphate into xanthine-5'-monophosphate, which is then converted into guanosine-5'-monophosphate.^[5] IMPDH2 has been identified as an intracellular target of the natural product sanglifehrin A.^[8]

Clinical significance

This gene is up-regulated in some neoplasms, suggesting it may play a role in malignant transformation.^[5]

Related Research Articles

<span class="mw-page-title-main">Inosine</span> Chemical compound

Inosine is a nucleoside that is formed when hypoxanthine is attached to a ribose ring (also known as a ribofuranose) via a β-N₉-glycosidic bond. It was discovered in 1965 in analysis of RNA transferase. Inosine is commonly found in tRNAs and is essential for proper translation of the genetic code in wobble base pairs.

Mycophenolic acid is an immunosuppressant medication used to prevent rejection following organ transplantation and to treat autoimmune conditions such as Crohn's disease and lupus. Specifically it is used following kidney, heart, and liver transplantation. It can be given by mouth or by injection into a vein. It comes as mycophenolate sodium and mycophenolate mofetil.

AMP deaminase 1 is an enzyme that in humans is encoded by the AMPD1 gene.

Purine metabolism refers to the metabolic pathways to synthesize and break down purines that are present in many organisms.

<span class="mw-page-title-main">GMP synthase</span>

Guanosine monophosphate synthetase, also known as GMPS is an enzyme that converts xanthosine monophosphate to guanosine monophosphate.

<span class="mw-page-title-main">GMP reductase</span> Class of enzymes

GMP reductase EC 1.7.1.7 is an enzyme that catalyzes the irreversible and NADPH-dependent reductive deamination of GMP into IMP.

Bifunctional purine biosynthesis protein PURH is a protein that in humans is encoded by the ATIC gene.

Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-3 is a protein that in humans is encoded by the GNB3 gene.

In enzymology, an adenosine-phosphate deaminase (EC 3.5.4.17) is an enzyme that catalyzes the chemical reaction

Alcohol dehydrogenase 4 is an enzyme that in humans is encoded by the ADH4 gene.

Concentrative nucleoside transporter 2 (CNT2) is a protein that in humans is encoded by the SLC28A2 gene.

Inosine triphosphate pyrophosphatase is an enzyme that in humans is encoded by the ITPA gene, by the rdgB gene in bacteria E.coli and the HAM1 gene in yeast S. cerevisiae; the protein is also encoded by some RNA viruses of the Potyviridae family. Two transcript variants encoding two different isoforms have been found for this gene. Also, at least two other transcript variants have been identified which are probably regulatory rather than protein-coding.

Inosine-5′-monophosphate dehydrogenase (IMPDH) is a purine biosynthetic enzyme that catalyzes the nicotinamide adenine dinucleotide (NAD⁺)-dependent oxidation of inosine monophosphate (IMP) to xanthosine monophosphate (XMP), the first committed and rate-limiting step towards the de novo biosynthesis of guanine nucleotides from IMP. IMPDH is a regulator of the intracellular guanine nucleotide pool, and is therefore important for DNA and RNA synthesis, signal transduction, energy transfer, glycoprotein synthesis, as well as other process that are involved in cellular proliferation.

Inosine-5'-monophosphate dehydrogenase 1, also known as IMP dehydrogenase 1, is an enzyme that in humans is encoded by the IMPDH1 gene.

5-hydroxytryptamine (serotonin) receptor 3B, also known as HTR3B, is a human gene. The protein encoded by this gene is a subunit of the 5-HT3 receptor.

Aldehyde dehydrogenase 1 family, member A3, also known as ALDH1A3 or retinaldehyde dehydrogenase 3 (RALDH3), is an enzyme that in humans is encoded by the ALDH1A3 gene,

UDP-glucuronosyltransferase 1-9 is an enzyme that in humans is encoded by the UGT1A9 gene.

UDP glucuronosyltransferase 2 family, polypeptide B1, also known as UGT2B1, is an enzyme that in humans is encoded by the UGT2B1 gene.

Monofunctional C1-tetrahydrofolate synthase, mitochondrial also known as formyltetrahydrofolate synthetase, is an enzyme that in humans is encoded by the MTHFD1L gene.

The gua operon is responsible for regulating the synthesis of guanosine mono phosphate (GMP), a purine nucleotide, from inosine monophosphate. It consists of two structural genes guaB (encodes for IMP dehydrogenase or and guaA apart from the promoter and operator region.

References

1 2 3 GRCh38: Ensembl release 89: ENSG00000178035 - Ensembl, May 2017
1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000062867 - Ensembl, May 2017
↑ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
↑ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
1 2 3 "Entrez Gene: IMP (inosine monophosphate) dehydrogenase 2".
↑ Natsumeda Y, Ohno S, Kawasaki H, Konno Y, Weber G, Suzuki K (March 1990). "Two distinct cDNAs for human IMP dehydrogenase". J. Biol. Chem. 265 (9): 5292–5. doi: 10.1016/S0021-9258(19)34120-1 . PMID 1969416.
↑ Kost-Alimova MV, Glesne DA, Huberman E, Zelenin AV (1998). "Assignment1 of inosine '-monophosphate dehydrogenase type 2 (IMPDH2) to human chromosome band 3p21.2 by in situ hybridization". Cytogenet. Cell Genet. 82 (3–4): 145–6. doi:10.1159/000015088. PMID 9858805. S2CID 46764436.
↑ Pua KH, Stiles DT, Sowa ME, Verdine GL (10 January 2017). "IMPDH2 Is an Intracellular Target of the Cyclophilin A and Sanglifehrin A Complex". Cell Rep. 18 (2): 432–442. doi: 10.1016/j.celrep.2016.12.030 . PMID 28076787.

Garat A, Cauffiez C, Hamdan-Khalil R, et al. (2009). "IMPDH2 genetic polymorphism: a promoter single-nucleotide polymorphism disrupts a cyclic adenosine monophosphate responsive element". Genet Test Mol Biomarkers. 13 (6): 841–7. doi:10.1089/gtmb.2009.0096. PMID 19810816.
Wang J, Zeevi A, Webber S, et al. (2007). "A novel variant L263F in human inosine 5'-monophosphate dehydrogenase 2 is associated with diminished enzyme activity". Pharmacogenet. Genomics. 17 (4): 283–90. doi:10.1097/FPC.0b013e328012b8cf. PMID 17496727. S2CID 21301713.
So HC, Fong PY, Chen RY, et al. (2010). "Identification of neuroglycan C and interacting partners as potential susceptibility genes for schizophrenia in a Southern Chinese population". Am. J. Med. Genet. B Neuropsychiatr. Genet. 153B (1): 103–13. doi:10.1002/ajmg.b.30961. PMID 19367581. S2CID 20522961.
Grinyó J, Vanrenterghem Y, Nashan B, et al. (2008). "Association of four DNA polymorphisms with acute rejection after kidney transplantation". Transpl. Int. 21 (9): 879–91. doi:10.1111/j.1432-2277.2008.00679.x. PMID 18444945. S2CID 42432512.
Ohmann EL, Burckart GJ, Brooks MM, et al. (2010). "Genetic polymorphisms influence mycophenolate mofetil-related adverse events in pediatric heart transplant patients". The Journal of Heart and Lung Transplantation. 29 (5): 509–516. doi:10.1016/j.healun.2009.11.602. PMID 20061166.
Sombogaard F, van Schaik RH, Mathot RA, et al. (2009). "Interpatient variability in IMPDH activity in MMF-treated renal transplant patients is correlated with IMPDH type II 3757T > C polymorphism". Pharmacogenet. Genomics. 19 (8): 626–34. doi:10.1097/FPC.0b013e32832f5f1b. PMID 19617864. S2CID 41882586.
Fellenberg J, Bernd L, Delling G, et al. (2007). "Prognostic significance of drug-regulated genes in high-grade osteosarcoma". Mod. Pathol. 20 (10): 1085–94. doi: 10.1038/modpathol.3800937 . PMID 17660802.
Lim J, Hao T, Shaw C, et al. (2006). "A protein-protein interaction network for human inherited ataxias and disorders of Purkinje cell degeneration". Cell. 125 (4): 801–14. doi: 10.1016/j.cell.2006.03.032 . PMID 16713569. S2CID 13709685.
He Y, Mou Z, Li W, et al. (2009). "Identification of IMPDH2 as a tumor-associated antigen in colorectal cancer using immunoproteomics analysis". Int J Colorectal Dis. 24 (11): 1271–9. doi:10.1007/s00384-009-0759-2. PMID 19597826. S2CID 24143679.
Peñuelas S, Noé V, Ciudad CJ (2005). "Modulation of IMPDH2, survivin, topoisomerase I and vimentin increases sensitivity to methotrexate in HT29 human colon cancer cells". FEBS J. 272 (3): 696–710. doi: 10.1111/j.1742-4658.2004.04504.x . PMID 15670151. S2CID 43226077.
Winnicki W, Weigel G, Sunder-Plassmann G, et al. (2010). "An inosine 5'-monophosphate dehydrogenase 2 single-nucleotide polymorphism impairs the effect of mycophenolic acid". Pharmacogenomics J. 10 (1): 70–6. doi: 10.1038/tpj.2009.43 . PMID 19770842.
Patel CG, Richman K, Yang D, et al. (2007). "Effect of diabetes mellitus on mycophenolate sodium pharmacokinetics and inosine monophosphate dehydrogenase activity in stable kidney transplant recipients". Ther Drug Monit. 29 (6): 735–42. doi:10.1097/FTD.0b013e31815d8ace. PMC 4082794 . PMID 18043470.
Sanquer S, Maison P, Tomkiewicz C, et al. (2008). "Expression of inosine monophosphate dehydrogenase type I and type II after mycophenolate mofetil treatment: a 2-year follow-up in kidney transplantation". Clin. Pharmacol. Ther. 83 (2): 328–35. doi:10.1038/sj.clpt.6100300. PMID 17713475. S2CID 44919245.
Mohamed MF, Frye RF, Langaee TY (2008). "Interpopulation variation frequency of human inosine 5'-monophosphate dehydrogenase type II (IMPDH2) genetic polymorphisms". Genet. Test. 12 (4): 513–6. doi:10.1089/gte.2008.0049. PMID 18976158.
Mannava S, Grachtchouk V, Wheeler LJ, et al. (2008). "Direct role of nucleotide metabolism in C-MYC-dependent proliferation of melanoma cells". Cell Cycle. 7 (15): 2392–400. doi:10.4161/cc.6390. PMC 3744895 . PMID 18677108.
Chen L, Petrelli R, Olesiak M, et al. (2008). "Bis(sulfonamide) isosters of mycophenolic adenine dinucleotide analogues: inhibition of inosine monophosphate dehydrogenase". Bioorg. Med. Chem. 16 (15): 7462–9. doi:10.1016/j.bmc.2008.06.003. PMID 18583139.
Guo D, Han J, Adam BL, et al. (2005). "Proteomic analysis of SUMO4 substrates in HEK293 cells under serum starvation-induced stress". Biochem. Biophys. Res. Commun. 337 (4): 1308–18. doi:10.1016/j.bbrc.2005.09.191. PMID 16236267.
Kudo M, Saito Y, Sasaki T, et al. (2009). "Genetic variations in the HGPRT, ITPA, IMPDH1, IMPDH2, and GMPS genes in Japanese individuals". Drug Metab. Pharmacokinet. 24 (6): 557–64. doi:10.2133/dmpk.24.557. PMID 20045992.
Ewing RM, Chu P, Elisma F, et al. (2007). "Large-scale mapping of human protein-protein interactions by mass spectrometry". Mol. Syst. Biol. 3 (1): 89. doi:10.1038/msb4100134. PMC 1847948 . PMID 17353931.

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[refGRCh38Ensembl-1] 1 2 3 GRCh38: Ensembl release 89: ENSG00000178035 - Ensembl, May 2017

[refGRCm38Ensembl-2] 1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000062867 - Ensembl, May 2017

[3] "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.

[4] "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.

[entrez-5] 1 2 3 "Entrez Gene: IMP (inosine monophosphate) dehydrogenase 2".

[pmid1969416-6] Natsumeda Y, Ohno S, Kawasaki H, Konno Y, Weber G, Suzuki K (March 1990). "Two distinct cDNAs for human IMP dehydrogenase". J. Biol. Chem. 265 (9): 5292–5. doi: 10.1016/S0021-9258(19)34120-1 . PMID 1969416.

[pmid9858805-7] Kost-Alimova MV, Glesne DA, Huberman E, Zelenin AV (1998). "Assignment1 of inosine '-monophosphate dehydrogenase type 2 (IMPDH2) to human chromosome band 3p21.2 by in situ hybridization". Cytogenet. Cell Genet. 82 (3–4): 145–6. doi:10.1159/000015088. PMID 9858805. S2CID 46764436.

[sanglifehrin-8] Pua KH, Stiles DT, Sowa ME, Verdine GL (10 January 2017). "IMPDH2 Is an Intracellular Target of the Cyclophilin A and Sanglifehrin A Complex". Cell Rep. 18 (2): 432–442. doi: 10.1016/j.celrep.2016.12.030 . PMID 28076787.

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v t e Oxidoreductases: alcohol oxidoreductases (EC 1.1)
1.1.1: NAD/NADP acceptor	3-hydroxyacyl-CoA dehydrogenase 3-hydroxybutyryl-CoA dehydrogenase Alcohol dehydrogenase Aldo-keto reductase 1A1 1B1 1B10 1C1 1C3 1C4 7A2 Aldose reductase Beta-Ketoacyl ACP reductase Carbohydrate dehydrogenases Carnitine dehydrogenase D-malate dehydrogenase (decarboxylating) DXP reductoisomerase Glucose-6-phosphate dehydrogenase Glycerol-3-phosphate dehydrogenase HMG-CoA reductase IMP dehydrogenase Isocitrate dehydrogenase Lactate dehydrogenase L-threonine dehydrogenase L-xylulose reductase Malate dehydrogenase Malate dehydrogenase (decarboxylating) Malate dehydrogenase (NADP+) Malate dehydrogenase (oxaloacetate-decarboxylating) Malate dehydrogenase (oxaloacetate-decarboxylating) (NADP+) Phosphogluconate dehydrogenase Sorbitol dehydrogenase Hydroxysteroid dehydrogenase: 3β 3β-HSD NSDHL 11β 11β-HSD1 11β-HSD2 17β
1.1.2: cytochrome acceptor	D-lactate dehydrogenase (cytochrome) D-lactate dehydrogenase (cytochrome c-553) Mannitol dehydrogenase (cytochrome)
1.1.3: oxygen acceptor	Glucose oxidase L-gulonolactone oxidase Xanthine oxidase Alcohol oxidase
1.1.4: disulfide as acceptor	Vitamin K epoxide reductase Vitamin-K-epoxide reductase (warfarin-insensitive)
1.1.5: quinone/similar acceptor	Malate dehydrogenase (quinone) Quinoprotein glucose dehydrogenase
1.1.99: other acceptors	Choline dehydrogenase L2HGDH

v t e Enzymes
Activity	Active site Binding site Catalytic triad Oxyanion hole Enzyme promiscuity Diffusion-limited enzyme Cofactor Enzyme catalysis
Regulation	Allosteric regulation Cooperativity Enzyme inhibitor Enzyme activator
Classification	EC number Enzyme superfamily Enzyme family List of enzymes
Kinetics	Enzyme kinetics Eadie–Hofstee diagram Hanes–Woolf plot Lineweaver–Burk plot Michaelis–Menten kinetics
Types	EC1 Oxidoreductases (list) EC2 Transferases (list) EC3 Hydrolases (list) EC4 Lyases (list) EC5 Isomerases (list) EC6 Ligases (list) EC7 Translocases (list)

IMPDH2

Contents

Function

Clinical significance

See also

Related Research Articles

References

Further reading