G2Cdb::Gene report

Gene id
G00002193
Gene symbol
IDH2 (HGNC)
Species
Homo sapiens
Description
isocitrate dehydrogenase 2 (NADP+), mitochondrial
Orthologue
G00000944 (Mus musculus)

Databases (7)

Gene
ENSG00000182054 (Ensembl human gene)
3418 (Entrez Gene)
824 (G2Cdb plasticity & disease)
IDH2 (GeneCards)
Literature
147650 (OMIM)
Marker Symbol
HGNC:5383 (HGNC)
Protein Sequence
P48735 (UniProt)

Literature (27)

Pubmed - other

  • Diagnostic use of IDH1/2 mutation analysis in routine clinical testing of formalin-fixed, paraffin-embedded glioma tissues.

    Horbinski C, Kofler J, Kelly LM, Murdoch GH and Nikiforova MN

    Department of Pathology, University of Kentucky, Kentucky, University of Pittsburgh, Pittsburgh, PA 15213, USA.

    Mutations in isocitrate dehydrogenase enzyme isoforms 1 (IDH1) and 2 (IDH2) have been identified in many adult astrocytomas and oligodendrogliomas. These mutations are targeted to specific codons (e.g. R132 in IDH1 and R172 in IDH2), making assays to detect them in clinical specimens feasible. We describe a simple and accurate molecular assay for detection of IDH1/2 mutations on routine formalin-fixed paraffin-embedded tissues. Using this polymerase chain reaction-based assay, we tested 75 glial neoplasms and 57 nonneoplastic conditions that can mimic gliomas including radiation changes, viral infections, and infarcts. Of the gliomas, 37 (49%) were positive for IDH1 or IDH2 mutations; the most common mutation was IDH1 (97%). Two of 12 gangliogliomas were positive for IDH1 mutation, and both had unfavorable clinical outcomes (p < 0.03). None of the nonneoplastic cases were positive for IDH mutations. The assay detected IDH mutations in biopsy material containing mostly glioma and in concomitant near-miss stereotactic core biopsies that were otherwise equivocal for the presence of glioma by light microscopy. These results indicate that testing for IDH1/2 mutations can be effectively performed in a clinical setting and can enhance the accuracy of diagnosis of gliomas when traditional diagnostic methods are not definitive.

    Journal of neuropathology and experimental neurology 2009;68;12;1319-25

  • IDH1 mutations in low-grade astrocytomas predict survival but not response to temozolomide.

    Dubbink HJ, Taal W, van Marion R, Kros JM, van Heuvel I, Bromberg JE, Zonnenberg BA, Zonnenberg CB, Postma TJ, Gijtenbeek JM, Boogerd W, Groenendijk FH, Smitt PA, Dinjens WN and van den Bent MJ

    Department of Pathology, Josephine Nefkens Institute, Erasmus MC, University Medical Center, Rotterdam, The Netherlands.

    Background: Mutations in isocitrate dehydrogenase 1 and 2 (IDH1 and IDH2) have been implicated in tumorigenesis of gliomas. Patients with high-grade astrocytomas with IDH1 or IDH2 mutations were reported to have a better survival, but it is unknown if this improved survival also holds for low-grade astrocytoma and whether these mutations predict outcome to specific treatment.

    Methods: We retrospectively investigated the correlation of IDH1 and IDH2 mutations with overall survival and response to temozolomide in a cohort of patients with dedifferentiated low-grade astrocytomas treated with temozolomide at the time of progression after radiotherapy.

    Results: IDH1 mutations were present in 86% of the 49 progressive astrocytomas. No mutations in IDH2 were found. Presence of IDH1 mutations were early events and significantly improved overall survival (median survival 48 vs 98 months), but did not affect outcome of temozolomide treatment.

    Conclusion: These results indicate that IDH1 mutations identify a subgroup of gliomas with an improved survival, but are unrelated to the temozolomide response.

    Neurology 2009;73;21;1792-5

  • Absence of IDH2 codon 172 mutation in common human cancers.

    Park SW, Chung NG, Han JY, Eom HS, Lee JY, Yoo NJ and Lee SH

    International journal of cancer 2009;125;10;2485-6

  • Diagnostic and prognostic markers in gliomas.

    Ducray F, El Hallani S and Idbaih A

    Unité Inserm U842, Service de Neurologie B, Hôpital Neurologique, Université Claude Bernard Lyon 1, Lyon, France. francois.ducray@chu-lyon.fr

    This review summarizes recent studies on diagnostic and prognostic markers in gliomas such as the BRAF fusion gene in pilocytic astrocytomas and 1p/19q codeletion, O-6-methylguanine-DNA methyltransferase status and isocitrate dehydrogenase 1 (IDH1)/IDH2 mutations in diffuse gliomas.

    In pilocytic astrocytomas, the BRAF fusion gene has been recently identified as a specific and frequent event leading to potentially targetable mitogen-activated protein kinase pathway activation. In grade II/III gliomas and in glioblastomas, chromosome 1p/19q codeletion and O-6-methylguanine-DNA methyltransferase status remain the most important prognostic and predictive markers. Recently identified mutations in IDH1/IDH2, however, are specific for diffuse gliomas, occur frequently in grade II/III gliomas and are of prognostic value in grade III gliomas, as well in glioblastomas in which they characterize secondary glioblastomas.

    Summary: Extensive molecular studies have enabled the discovery of new diagnostic and prognostic markers that are refining the histomolecular classification of gliomas.

    Current opinion in oncology 2009;21;6;537-42

  • Analysis of IDH1 and IDH2 mutations in Japanese glioma patients.

    Sonoda Y, Kumabe T, Nakamura T, Saito R, Kanamori M, Yamashita Y, Suzuki H and Tominaga T

    Department of Neurosurgery, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan. sono@nsg.med.tohoku.ac.jp

    A recent study reported on mutations in the active site of the isocitrate dehydrogenase 1 (IDH1) gene in several types of gliomas. All mutations detected resulted in an amino acid exchange at position 132. We analyzed the genomic region spanning wild-type R132 of IDH1 by direct sequencing in 125 glial tumors. A total of 39 IDH1 mutations were observed. Mutations of the IDH2 gene, homologous to IDH1, were often detected in gliomas without IDH1 mutations. In the present study, R172 mutation of the IDH2 gene was detected in one anaplastic astrocytoma. IDH1 or IDH2 mutations were frequently in oligodendrogliomas (67%), anaplastic astrocytomas (62%), anaplastic oligoastrocytomas (75%), anaplastic oligodendrogliomas (50%), secondary glioblastomas (67%), gangliogliomas (38%), and anaplastic gangliogliomas (60%). Primary glioblastomas were characterized by a low frequency of mutations (5%) at amino acid position 132 of IDH1. Mutations of the IDH1 or IDH2 genes were significantly associated with improved outcome in patients with anaplastic astrocytomas. Our data suggest that IDH1 or IDH2 mutation plays a role in early tumor progression of several types of glioma and might arise from a common glial precursor. The infrequency of IDH1 mutation in primary glioblastomas revealed that these subtypes are genetically distinct entities from other glial tumors.

    Cancer science 2009;100;10;1996-8

  • Type and frequency of IDH1 and IDH2 mutations are related to astrocytic and oligodendroglial differentiation and age: a study of 1,010 diffuse gliomas.

    Hartmann C, Meyer J, Balss J, Capper D, Mueller W, Christians A, Felsberg J, Wolter M, Mawrin C, Wick W, Weller M, Herold-Mende C, Unterberg A, Jeuken JW, Wesseling P, Reifenberger G and von Deimling A

    Department of Neuropathology, Institute of Pathology, Ruprecht-Karls-Universität Heidelberg, Im Neuenheimer Feld 220/221, Heidelberg, Germany.

    Somatic mutations in the IDH1 gene encoding cytosolic NADP+-dependent isocitrate dehydrogenase have been shown in the majority of astrocytomas, oligodendrogliomas and oligoastrocytomas of WHO grades II and III. IDH2 encoding mitochondrial NADP+-dependent isocitrate dehydrogenase is also mutated in these tumors, albeit at much lower frequencies. Preliminary data suggest an importance of IDH1 mutation for prognosis showing that patients with anaplastic astrocytomas, oligodendrogliomas and oligoastrocytomas harboring IDH1 mutations seem to fare much better than patients without this mutation in their tumors. To determine mutation types and their frequencies, we examined 1,010 diffuse gliomas. We detected 716 IDH1 mutations and 31 IDH2 mutations. We found 165 IDH1 (72.7%) and 2 IDH2 mutations (0.9%) in 227 diffuse astrocytomas WHO grade II, 146 IDH1 (64.0%) and 2 IDH2 mutations (0.9%) in 228 anaplastic astrocytomas WHO grade III, 105 IDH1 (82.0%) and 6 IDH2 mutations (4.7%) in 128 oligodendrogliomas WHO grade II, 121 IDH1 (69.5%) and 9 IDH2 mutations (5.2%) in 174 anaplastic oligodendrogliomas WHO grade III, 62 IDH1 (81.6%) and 1 IDH2 mutations (1.3%) in 76 oligoastrocytomas WHO grade II and 117 IDH1 (66.1%) and 11 IDH2 mutations (6.2%) in 177 anaplastic oligoastrocytomas WHO grade III. We report on an inverse association of IDH1 and IDH2 mutations in these gliomas and a non-random distribution of the mutation types within the tumor entities. IDH1 mutations of the R132C type are strongly associated with astrocytoma, while IDH2 mutations predominantly occur in oligodendroglial tumors. In addition, patients with anaplastic glioma harboring IDH1 mutations were on average 6 years younger than those without these alterations.

    Acta neuropathologica 2009;118;4;469-74

  • Mutations of IDH1 and IDH2 are not detected in brain metastases of colorectal cancer.

    Holdhoff M, Parsons DW and Diaz LA

    Journal of neuro-oncology 2009;94;2;297

  • IDH1 and IDH2 mutations in gliomas.

    Ducray F, Marie Y and Sanson M

    The New England journal of medicine 2009;360;21;2248-9; author reply 2249

  • IDH1 and IDH2 mutations in gliomas.

    Yan H, Parsons DW, Jin G, McLendon R, Rasheed BA, Yuan W, Kos I, Batinic-Haberle I, Jones S, Riggins GJ, Friedman H, Friedman A, Reardon D, Herndon J, Kinzler KW, Velculescu VE, Vogelstein B and Bigner DD

    Department of Pathology, Pediatric Brain Tumor Foundation Institute, Duke University Medical Center, Durham, NC 27710, USA. yan00002@mc.duke.edu

    Background: A recent genomewide mutational analysis of glioblastomas (World Health Organization [WHO] grade IV glioma) revealed somatic mutations of the isocitrate dehydrogenase 1 gene (IDH1) in a fraction of such tumors, most frequently in tumors that were known to have evolved from lower-grade gliomas (secondary glioblastomas).

    Methods: We determined the sequence of the IDH1 gene and the related IDH2 gene in 445 central nervous system (CNS) tumors and 494 non-CNS tumors. The enzymatic activity of the proteins that were produced from normal and mutant IDH1 and IDH2 genes was determined in cultured glioma cells that were transfected with these genes.

    Results: We identified mutations that affected amino acid 132 of IDH1 in more than 70% of WHO grade II and III astrocytomas and oligodendrogliomas and in glioblastomas that developed from these lower-grade lesions. Tumors without mutations in IDH1 often had mutations affecting the analogous amino acid (R172) of the IDH2 gene. Tumors with IDH1 or IDH2 mutations had distinctive genetic and clinical characteristics, and patients with such tumors had a better outcome than those with wild-type IDH genes. Each of four tested IDH1 and IDH2 mutations reduced the enzymatic activity of the encoded protein.

    Conclusions: Mutations of NADP(+)-dependent isocitrate dehydrogenases encoded by IDH1 and IDH2 occur in a majority of several types of malignant gliomas.

    Funded by: NCI NIH HHS: 2P30-CA-14236, 5P50-CA-108786, 5R37-CA-11898, CA121113, CA43460, CA57345, P30 CA014236, P50 CA062924-150012, P50 CA108786, R01 CA057345, R01 CA118822, R01 CA121113, R01 CA121113-04, R01 CA140316, R01CA118822, R37 CA011898, R37 CA043460, R37 CA043460-26, R37 CA043460-27, R37 CA057345, R37 CA057345-17, R37CA11898-34; NINDS NIH HHS: 5P50-NS-20023, NS20023-21, P50 NS020023

    The New England journal of medicine 2009;360;8;765-73

  • Inactivation of mitochondrial NADP+-dependent isocitrate dehydrogenase by hypochlorous acid.

    Park SY, Lee SM, Shin SW and Park JW

    School of Life Sciences and Biotechnology, College of Natural Sciences, Kyungpook National University, Taegu, South Korea.

    Myeoloperoxidase catalyses the formation of hypochlorous acid (HOCl) via reaction of H(2)O(2) with Cl(-) ion. Although HOCl is known to play a major role in the human immune system by killing bacteria and other invading pathogens, excessive generation of this oxidant is known to cause damage to tissue. Recently, it was demonstrated that the control of mitochondrial redox balance and oxidative damage is one of the primary functions of mitochondrial NADP(+)-dependent isocitrate dehydrogenase (IDPm) to supply NADPH for antioxidant systems. This study investigated whether the IDPm would be a vulnerable target of HOCl as a purified enzyme and in intact cells. Loss of enzyme activity was observed and the inactivation of IDPm was reversed by thiols. Transfection of HeLa cells with an IDPm small interfering RNA (siRNA) markedly enhanced HOCl-induced oxidative damage to cells. The HOCl-mediated damage to IDPm may result in the perturbation of the cellular antioxidant defense mechanisms and subsequently lead to a pro-oxidant condition.

    Free radical research 2008;42;5;467-73

  • Toward a confocal subcellular atlas of the human proteome.

    Barbe L, Lundberg E, Oksvold P, Stenius A, Lewin E, Björling E, Asplund A, Pontén F, Brismar H, Uhlén M and Andersson-Svahn H

    Department of Biotechnology, AlbaNova University Center, Royal Institute of Technology, SE-106 91 Stockholm, Sweden.

    Information on protein localization on the subcellular level is important to map and characterize the proteome and to better understand cellular functions of proteins. Here we report on a pilot study of 466 proteins in three human cell lines aimed to allow large scale confocal microscopy analysis using protein-specific antibodies. Approximately 3000 high resolution images were generated, and more than 80% of the analyzed proteins could be classified in one or multiple subcellular compartment(s). The localizations of the proteins showed, in many cases, good agreement with the Gene Ontology localization prediction model. This is the first large scale antibody-based study to localize proteins into subcellular compartments using antibodies and confocal microscopy. The results suggest that this approach might be a valuable tool in conjunction with predictive models for protein localization.

    Molecular & cellular proteomics : MCP 2008;7;3;499-508

  • Silencing of mitochondrial NADP+-dependent isocitrate dehydrogenase by small interfering RNA enhances heat shock-induced apoptosis.

    Shin SW, Kil IS and Park JW

    School of Life Sciences and Biotechnology, College of Natural Sciences, Kyungpook National University, Taegu 702-701, Republic of Korea.

    Heat shock may increase oxidative stress due to increased production of reactive oxygen species and/or the promotion of cellular oxidation events. Mitochondrial NADP(+)-dependent isocitrate dehydrogenase (IDPm) produces NADPH, an essential reducing equivalent for the antioxidant system. In this report, we demonstrate that silencing of IDPm expression in HeLa cells greatly enhances apoptosis induced by heat shock. Transfection of HeLa cells with an IDPm small interfering RNA (siRNA) markedly decreased activity of IDPm, enhancing the susceptibility of heat shock-induced apoptosis reflected by morphological evidence of apoptosis, DNA fragmentation, cellular redox status, mitochondria redox status and function, and the modulation of apoptotic marker proteins. These results indicate that IDPm may play an important role in regulating the apoptosis induced by heat shock and the sensitizing effect of IDPm siRNA on the apoptotic cell death of HeLa cells offers the possibility of developing a modifier of cancer therapy.

    Biochemical and biophysical research communications 2008;366;4;1012-8

  • Small interfering RNA-mediated silencing of mitochondrial NADP+-dependent isocitrate dehydrogenase enhances the sensitivity of HeLa cells toward tumor necrosis factor-alpha and anticancer drugs.

    Kil IS, Kim SY, Lee SJ and Park JW

    School of Life Sciences and Biotechnology, College of Natural Sciences, Kyungpook National University, Taegu 702-701, Korea.

    Tumor necrosis factor-alpha (TNF-alpha) and several anticancer drugs induce the production of reactive oxygen species, which play an important causative role in apoptotic cell death. Recently, we demonstrated that the control of mitochondrial redox balance and the cellular defense against oxidative damage is one of the primary functions of mitochondrial NADP(+)-dependent isocitrate dehydrogenase (IDPm) by supplying NADPH for antioxidant systems. In the present report, we show that silencing of IDPm expression in HeLa cells greatly enhances apoptosis induced by TNF-alpha and anticancer drugs. Transfection of HeLa cells with an IDPm small interfering RNA (siRNA) markedly decreased activity of IDPm, enhancing the susceptibility of anticancer agent-induced apoptosis reflected by morphological evidence of apoptosis, DNA fragmentation, cellular redox status, mitochondria redox status and function, and the modulation of apoptotic marker proteins. These results indicate that IDPm may play an important role in regulating the apoptosis induced by TNF-alpha and anticancer drugs and the sensitizing effect of IDPm siRNA on the apoptotic cell death of HeLa cells offers the possibility of developing a modifier of cancer chemotherapy.

    Free radical biology & medicine 2007;43;8;1197-207

  • Insulin-dependent interactions of proteins with GLUT4 revealed through stable isotope labeling by amino acids in cell culture (SILAC).

    Foster LJ, Rudich A, Talior I, Patel N, Huang X, Furtado LM, Bilan PJ, Mann M and Klip A

    Center for Experimental BioInformatics (CEBI), Department of Biochemistry and Molecular Biology, University of Southern Denmark, Campusvej 55, DK-5230 Odense M, Denmark.

    The insulin-regulated glucose transporter (GLUT4) translocates to the plasma membrane in response to insulin in order to facilitate the postprandial uptake of glucose into fat and muscle cells. While early insulin receptor signaling steps leading to this translocation are well defined, the integration of signaling and regulation of GLUT4 traffic remains elusive. Several lines of evidence suggest an important role for the actin cytoskeleton and for protein-protein interactions in regulating GLUT4 localization by insulin. Here, we applied stable isotope labeling by amino acids in cell culture (SILAC) to identify proteins that interact with GLUT4 in an insulin-regulated manner. Myc-tagged GLUT4 (GLUT4myc) stably expressed in L6 myotubes was immunoprecipitated via the myc epitope from total membranes isolated from basal and insulin-stimulated cells grown in medium containing normal isotopic abundance leucine or deuterated leucine, respectively. Proteins coprecipitating with GLUT4myc were analyzed by liquid chromatography/ tandem mass spectrometry. Of 603 proteins quantified, 36 displayed an insulin-dependent change of their interaction with GLUT4myc of more than 1.5-fold in either direction. Several cytoskeleton-related proteins were elevated in immunoprecipates from insulin-treated cells, whereas components of the ubiquitin-proteasome degradation system were generally reduced. Proteins participating in vesicle traffic also displayed insulin-regulated association. Of cytoskeleton-related proteins, alpha-actinin-4 recovery in GLUT4 immunoprecipitates rose in response to insulin 2.1 +/- 0.5-fold by SILAC and 2.9 +/- 0.8-fold by immunoblotting. Insulin caused GLUT4 and alpha-actinin-4 co-localization as revealed by confocal immunofluorescence microscopy. We conclude that insulin elicits changes in interactions between diverse proteins and GLUT4, and that cytoskeletal proteins, notably alpha-actinin-4, associate with the transporter, potentially to facilitate its routing to the plasma membrane.

    Journal of proteome research 2006;5;1;64-75

  • The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).

    Gerhard DS, Wagner L, Feingold EA, Shenmen CM, Grouse LH, Schuler G, Klein SL, Old S, Rasooly R, Good P, Guyer M, Peck AM, Derge JG, Lipman D, Collins FS, Jang W, Sherry S, Feolo M, Misquitta L, Lee E, Rotmistrovsky K, Greenhut SF, Schaefer CF, Buetow K, Bonner TI, Haussler D, Kent J, Kiekhaus M, Furey T, Brent M, Prange C, Schreiber K, Shapiro N, Bhat NK, Hopkins RF, Hsie F, Driscoll T, Soares MB, Casavant TL, Scheetz TE, Brown-stein MJ, Usdin TB, Toshiyuki S, Carninci P, Piao Y, Dudekula DB, Ko MS, Kawakami K, Suzuki Y, Sugano S, Gruber CE, Smith MR, Simmons B, Moore T, Waterman R, Johnson SL, Ruan Y, Wei CL, Mathavan S, Gunaratne PH, Wu J, Garcia AM, Hulyk SW, Fuh E, Yuan Y, Sneed A, Kowis C, Hodgson A, Muzny DM, McPherson J, Gibbs RA, Fahey J, Helton E, Ketteman M, Madan A, Rodrigues S, Sanchez A, Whiting M, Madari A, Young AC, Wetherby KD, Granite SJ, Kwong PN, Brinkley CP, Pearson RL, Bouffard GG, Blakesly RW, Green ED, Dickson MC, Rodriguez AC, Grimwood J, Schmutz J, Myers RM, Butterfield YS, Griffith M, Griffith OL, Krzywinski MI, Liao N, Morin R, Morrin R, Palmquist D, Petrescu AS, Skalska U, Smailus DE, Stott JM, Schnerch A, Schein JE, Jones SJ, Holt RA, Baross A, Marra MA, Clifton S, Makowski KA, Bosak S, Malek J and MGC Project Team

    The National Institutes of Health's Mammalian Gene Collection (MGC) project was designed to generate and sequence a publicly accessible cDNA resource containing a complete open reading frame (ORF) for every human and mouse gene. The project initially used a random strategy to select clones from a large number of cDNA libraries from diverse tissues. Candidate clones were chosen based on 5'-EST sequences, and then fully sequenced to high accuracy and analyzed by algorithms developed for this project. Currently, more than 11,000 human and 10,000 mouse genes are represented in MGC by at least one clone with a full ORF. The random selection approach is now reaching a saturation point, and a transition to protocols targeted at the missing transcripts is now required to complete the mouse and human collections. Comparison of the sequence of the MGC clones to reference genome sequences reveals that most cDNA clones are of very high sequence quality, although it is likely that some cDNAs may carry missense variants as a consequence of experimental artifact, such as PCR, cloning, or reverse transcriptase errors. Recently, a rat cDNA component was added to the project, and ongoing frog (Xenopus) and zebrafish (Danio) cDNA projects were expanded to take advantage of the high-throughput MGC pipeline.

    Funded by: PHS HHS: N01-C0-12400

    Genome research 2004;14;10B;2121-7

  • Exploring proteomes and analyzing protein processing by mass spectrometric identification of sorted N-terminal peptides.

    Gevaert K, Goethals M, Martens L, Van Damme J, Staes A, Thomas GR and Vandekerckhove J

    Department of Medical Protein Research, Flanders Interuniversity Institute for Biotechnology, Ghent University, A. Baertsoenkaai 3, B-9000 Ghent, Belgium. kris.gevaert@rug.ac.be

    Current non-gel techniques for analyzing proteomes rely heavily on mass spectrometric analysis of enzymatically digested protein mixtures. Prior to analysis, a highly complex peptide mixture is either separated on a multidimensional chromatographic system or it is first reduced in complexity by isolating sets of representative peptides. Recently, we developed a peptide isolation procedure based on diagonal electrophoresis and diagonal chromatography. We call it combined fractional diagonal chromatography (COFRADIC). In previous experiments, we used COFRADIC to identify more than 800 Escherichia coli proteins by tandem mass spectrometric (MS/MS) analysis of isolated methionine-containing peptides. Here, we describe a diagonal method to isolate N-terminal peptides. This reduces the complexity of the peptide sample, because each protein has one N terminus and is thus represented by only one peptide. In this new procedure, free amino groups in proteins are first blocked by acetylation and then digested with trypsin. After reverse-phase (RP) chromatographic fractionation of the generated peptide mixture, internal peptides are blocked using 2,4,6-trinitrobenzenesulfonic acid (TNBS); they display a strong hydrophobic shift and therefore segregate from the unaltered N-terminal peptides during a second identical separation step. N-terminal peptides can thereby be specifically collected for further liquid chromatography (LC)-MS/MS analysis. Omitting the acetylation step results in the isolation of non-lysine-containing N-terminal peptides from in vivo blocked proteins.

    Nature biotechnology 2003;21;5;566-9

  • Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library.

    Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K, Suyama A and Sugano S

    International and Interdisciplinary Studies, The University of Tokyo, Japan.

    Using 'oligo-capped' mRNA [Maruyama, K., Sugano, S., 1994. Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides. Gene 138, 171-174], whose cap structure was replaced by a synthetic oligonucleotide, we constructed two types of cDNA library. One is a 'full length-enriched cDNA library' which has a high content of full-length cDNA clones and the other is a '5'-end-enriched cDNA library', which has a high content of cDNA clones with their mRNA start sites. The 5'-end-enriched library was constructed especially for isolating the mRNA start sites of long mRNAs. In order to characterize these libraries, we performed one-pass sequencing of randomly selected cDNA clones from both libraries (84 clones for the full length-enriched cDNA library and 159 clones for the 5'-end-enriched cDNA library). The cDNA clones of the polypeptide chain elongation factor 1 alpha were most frequently (nine clones) isolated, and more than 80% of them (eight clones) contained the mRNA start site of the gene. Furthermore, about 80% of the cDNA clones of both libraries whose sequence matched with known genes had the known 5' ends or sequences upstream of the known 5' ends (28 out of 35 for the full length-enriched library and 51 out of 62 for the 5'-end-enriched library). The longest full-length clone of the full length-enriched cDNA library was about 3300 bp (among 28 clones). In contrast, seven clones (out of the 51 clones with the mRNA start sites) from the 5'-end-enriched cDNA library came from mRNAs whose length is more than 3500 bp. These cDNA libraries may be useful for generating 5' ESTs with the information of the mRNA start sites that are now scarce in the EST database.

    Gene 1997;200;1-2;149-56

  • Assignment of the human mitochondrial NADP(+)-specific isocitrate dehydrogenase (IDH2) gene to 15q26.1 by in situ hybridization.

    Oh IU, Inazawa J, Kim YO, Song BJ and Huh TL

    Department of Genetic Engineering, College of Natural Sciences, Kyungpook National University, Taegu, Korea.

    Genomics 1996;38;1;104-6

  • Expression of human mitochondrial NADP-dependent isocitrate dehydrogenase during lymphocyte activation.

    Luo H, Shan X and Wu J

    Laboratory of Nephrology and Transplantation Immunology, Notre-Dame Hospital Research Center, Montreal, Quebec, Canada.

    In the process of identifying genes involved in optimization of lymphocyte activation, we have cloned the human mitochondrial NADP-dependent isocitrate dehydrogenase (mNADP-IDH) cDNA. The cDNA and its deduced amino acid (AA) sequence had a high degree of homology with those of the porcine and bovine. The heart and muscle had the highest constitutive expression of the gene. The expression of steady-state mRNA in the resting T and B lymphocytes was low but was induced after mitogen stimulation. The mRNA levels peaked around 48 h and remained elevated at 72 h. At the protein level, the mitochondrial but not cytosolic NADP-IDH activity was augmented after the mitogen stimulation. There was no cell cycle-dependent fluctuation of mNADP-IDH expression in synchronized Jurkat cells. In T and B cells, rapamycin (RAPA) could repress the mitogen-stimulated mNADP-IDH expression, although most of the early or late phase activation-related genes including a G-protein beta subunit-related gene H12.3 were not affected by the drug. The restricted expression of the gene in certain tissues and the activation-related expression in lymphocytes suggest that this gene might be necessary for optimal functions in heart, muscle, and the activated lymphocytes.

    Journal of cellular biochemistry 1996;60;4;495-507

  • Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides.

    Maruyama K and Sugano S

    Institute of Medical Science, University of Tokyo, Japan.

    We have devised a method to replace the cap structure of a mRNA with an oligoribonucleotide (r-oligo) to label the 5' end of eukaryotic mRNAs. The method consists of removing the cap with tobacco acid pyrophosphatase (TAP) and ligating r-oligos to decapped mRNAs with T4 RNA ligase. This reaction was made cap-specific by removing 5'-phosphates of non-capped RNAs with alkaline phosphatase prior to TAP treatment. Unlike the conventional methods that label the 5' end of cDNAs, this method specifically labels the capped end of the mRNAs with a synthetic r-oligo prior to first-strand cDNA synthesis. The 5' end of the mRNA was identified quite simply by reverse transcription-polymerase chain reaction (RT-PCR).

    Gene 1994;138;1-2;171-4

  • Monoamine oxidase and other mitochondrial enzymes in density subpopulations of human platelets.

    Chamberlain KG and Penington DG

    University of Melbourne Department of Medicine, St. Vincent's Hospital, Melbourne, Australia.

    Normal human platelets have been separated according to density on continuous Percoll gradients and the platelet distribution divided into five fractions containing approximately equal numbers of platelets. The mean volumes and protein contents of the platelets in each fraction were found to correlate positively with density while the protein concentration did not differ significantly between the fractions. Four mitochondrial enzymes (monoamine oxidase, glutamate dehydrogenase, cytochrome oxidase and NADP-dependent isocitrate dehydrogenase) were assayed and their activities per unit volume were found to increase in a very similar monotonic fashion with platelet density. When MAO and GDH were assayed on the same set of density fractions the correlation between the two activities was very high (r = 0.94-1.00, p less than 0.001) and a similar close correlation was found between MAO and ICDH. The results support the hypothesis that high density platelets either have a higher concentration of mitochondria or have larger mitochondria than low density platelets.

    Thrombosis and haemostasis 1988;59;1;29-33

  • Assignment of cytoplasmic alpha-mannosidase (MANA) and confirmation of mitochondrial isocitrate dehydrogenase (IDHM) to the q11 leads to qter region of chromosome 15 in man.

    Champion MJ, Brown JA and Shows TB

    Cytogenetics and cell genetics 1978;22;1-6;498-502

  • Somatic cell genetic assignment of the human gene for mitochondrial NADP-linked isocitrate dehydrogenase to the long arm of chromosome 15.

    Shimizu N, Giles RE, Kucherlapati RS, Shimizu Y and Ruddle FH

    A double-immunodiffusion method has been developed to detect human mitochondrial NADP-linked isocitrate dehydrogenase (EC 1.1.1.42; designated as IDH-2) using rabbit antiserum against the relevant enzyme. The method allows one to distinguish human IDH-2 from its mouse counterpart in extracts from human-mouse somatic cell hybrids. A correlation was found between the expression of human IDH-2 and the presence of human chromosome 15 in a "panel" of eight independent hybrid clones. Analysis of human marker enzymes for 37 different clones revealed a syntenic relationship between IDH-2 and mannose phosphate isomerase (EC 5.3.1.8; MPI), which has been assigned to chromosome 15 (1). These results permit the assignment of the structural gene for human IDH-2 to human chromosome 15. IDH-2 and human cytoplasmic IDH (IDH-1) were found to be asyntenic. Evidence from hybrid clones carrying a human X/15 translocation chromosome indicates that the human IDH-2 gene can be localized to the q11-qter region of chromosome 15.

    Somatic cell genetics 1977;3;1;47-60

  • Assignment of a gene for human mitochondrial isocitrate dehydrogenase (ICD-M, EC 1.1.1.41) to chromosome 15.

    Grzeschik KH

    Segregation analysis of human biochemical markers and chromosomes in human-mouse somatic cell hybrids allowed to demonstrate synteny of ICDM with the genes for phosphomannose isomerase and pyruvate kinase and to assign the linkage group to human chromosome 15.

    Human genetics 1976;34;1;23-8

  • Human mitochondrial NADP-dependent isocitrate dehydrogenase in man-mouse somatic cell hybrids.

    Bruns GA, Eisenman RE and Gerald PS

    Human mitochondrial NADP-dependent isocitrate dehydrogenase (IDH-2) is expressed in man-mouse somatic cell hybrids as a dimeric molecule. The gene specifing this enzyme was observed to be syntenic with the mannose phosphate isomerase locus in the 56 primary man-mouse clones in this series. The human IDH-2 locus, therefore, may be assigned to chromosome 15.

    Cytogenetics and cell genetics 1976;17;4;200-11

  • Regulation of progesterone biosynthesis in human placental mitochondria by Krebs cycle metabolites.

    Klimek J, Boguslawski W, Tialowska B and Zelewski L

    1. 2-Oxoglutarate, succinate, fumarate, malate and citrate, cis-aconitate and isocitrate stimulate conversion of cholesterol to progesterone in human placental mitochondria. 2. The stimulatory effect of dicarboxylic and tricarboxylic acids depends on the activity of malate dehydrogenase (decarboxylating) (NADP+) (EC 1.1.1.40) and isocitrate dehydrogenase (NADP+) (EC 1.1.1.42), respectively.

    Acta biochimica Polonica 1976;23;2-3;185-92

Gene lists (5)

Gene List Source Species Name Description Gene count
L00000009 G2C Homo sapiens Human PSD Human orthologues of mouse PSD adapted from Collins et al (2006) 1080
L00000010 G2C Homo sapiens Human mitochondria Human orthologues of mouse mitochondria adapted from Collins et al (2006) 91
L00000016 G2C Homo sapiens Human PSP Human orthologues of mouse PSP adapted from Collins et al (2006) 1121
L00000059 G2C Homo sapiens BAYES-COLLINS-HUMAN-PSD-CONSENSUS Human cortex PSD consensus 748
L00000069 G2C Homo sapiens BAYES-COLLINS-HUMAN-PSD-FULL Human cortex biopsy PSD full list 1461
© G2C 2014. The Genes to Cognition Programme received funding from The Wellcome Trust and the EU FP7 Framework Programmes:
EUROSPIN (FP7-HEALTH-241498), SynSys (FP7-HEALTH-242167) and GENCODYS (FP7-HEALTH-241995).

Cookies Policy | Terms and Conditions. This site is hosted by Edinburgh University and the Genes to Cognition Programme.