The world's first wiki where authorship really matters (Nature Genetics, 2008). Due credit and reputation for authors. Imagine a global collaborative knowledge base for original thoughts. Search thousands of articles and collaborate with scientists around the globe.

wikigene or wiki gene protein drug chemical gene disease author authorship tracking collaborative publishing evolutionary knowledge reputation system wiki2.0 global collaboration genes proteins drugs chemicals diseases compound
Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)



Gene Review

GAPDH  -  glyceraldehyde-3-phosphate dehydrogenase

Homo sapiens

Synonyms: CDABP0047, G3PD, GAPD, Glyceraldehyde-3-phosphate dehydrogenase, HEL-S-162eP, ...
Welcome! If you are familiar with the subject of this article, you can contribute to this open access knowledge base by deleting incorrect information, restructuring or completely rewriting any text. Read more.

Disease relevance of GAPDH


Psychiatry related information on GAPDH


High impact information on GAPDH


Chemical compound and disease context of GAPDH


Biological context of GAPDH

  • Depletion of GAPDH or Siah1 by RNA interference diminishes nuclear translocation of mHtt [16].
  • We have isolated a GAPDH complementary DNA from human lung cancer cells and deduced the complete amino acid sequence of the encoded protein [1].
  • The ratio between oxidized and reduced glulathione and the oxidation-dependent inactivation of glyceraldehyde-3phosphate dehydrogenase (GAPDH) are considered independent markers of cellular reactive oxygen species homeostasis and redox state [17].
  • Thus, the RNA binding specificity of GAPDH as well as its localization within the cell merit its strong consideration as a protein important in the regulation of ARE-dependent mRNA turnover and translation in addition to its well described role in glycolysis [18].
  • The direct demonstration of ARE-specific binding protein activity localized to the NAD(+)-binding region of GAPDH supports the general concept that enzymes containing this domain may exhibit specific RNA binding activity and play additional roles in nucleic acid metabolism [18].

Anatomical context of GAPDH

  • Finally, cytoplasmic GAPDH was found in the polysomal fraction of T lymphocytes [18].
  • The elution of GAPDH from the membranes prevents the stimulation by the substrates, but not by exogenous ATP [19].
  • In animals and other heterotrophic eukaryotes, both enzymes are localized in the cytosol; in photosynthetic eukaryotes, GAPDH and TPI exist as isoenzymes that function in the glycolytic pathway of the cytosol and in the Calvin cycle of chloroplasts [20].
  • Here, we show that diatoms--photosynthetic protists that acquired their plastids through secondary symbiotic engulfment of a eukaryotic rhodophyte--possess an additional isoenzyme each of both GAPDH and TPI [20].
  • Surprisingly, these new forms are expressed as an TPI-GAPDH fusion protein which is imported into mitochondria prior to its assembly into a tetrameric bifunctional enzyme complex [20].

Associations of GAPDH with chemical compounds

  • While provocative, these findings do not address the selective neuronal loss in each of these disorders in light of the wide expression patterns of GAPDH and the respective polyglutamine containing proteins [21].
  • Further data demonstrated that the nuclear localization of GAPDH is regulated by ceramide in a cell cycle-dependent manner parallel with the inhibition of its telomere binding activity in response to ceramide [22].
  • Patch-clamp electrophysiology showed that GAPDH regulates K(ATP)-channel activity irrespective of high intracellular ATP, by producing 1,3-bisphosphoglycerate, a K(ATP)-channel opener [23].
  • Hexokinase plus glucose (agents that promote breakdown of ATP) prevent stimulation of Na transport by exogenous ATP but not by the substrates for GAPDH and PGK [19].
  • No effect on the expression of the apurinic endonuclease hAPE or the house-keeping gene GAPDH was observed at any of the concentrations of sodium dichromate investigated [24].
  • GAPDH enhanced the transcriptional activity of AR(T875A) activated by an antagonist such as hydroxyflutamide or cyproterone acetate [25].
  • Because GAPDH has four cysteine residues, including the active site Cys(149), we prepared the cysteine-substituted mutants C149S, C153S, C244A, C281S, and C149S/C281S to identify which is responsible for disulfide-bonded aggregation [26].

Physical interactions of GAPDH


Enzymatic interactions of GAPDH


Regulatory relationships of GAPDH

  • The treatment of cells with reduced human Trx stimulated the synthesis of GAPDH mRNA [32].
  • In some cases, FLT3 was expressed at levels equivalent to GAPDH in the absence of genomic amplification [33].
  • Both CP12 and CTE seem to regulate different photosynthetic GAPDH isoforms according to a common and ancient molecular mechanism [34].
  • CLDN1 mRNA was downregulated by 12-fold in the sample (tumour) group as compared with the control group using GAPDH as the reference gene [35].
  • RESULTS: AM/-actin and AM/GAPDH mRNA ratios were significantly lower in placental villi in preeclampsia than in controls (P<0.05) as were CGRP/-actin and CGRP/GAPDH mRNA ratios in chorionic plates (P<0.05) [36].

Other interactions of GAPDH


Analytical, diagnostic and therapeutic context of GAPDH


  1. Enhanced expression of a glyceraldehyde-3-phosphate dehydrogenase gene in human lung cancers. Tokunaga, K., Nakamura, Y., Sakata, K., Fujimori, K., Ohkubo, M., Sawada, K., Sakiyama, S. Cancer Res. (1987) [Pubmed]
  2. Reduction of glyceraldehyde-3-phosphate dehydrogenase activity in Alzheimer's disease and in Huntington's disease fibroblasts. Mazzola, J.L., Sirover, M.A. J. Neurochem. (2001) [Pubmed]
  3. Gene expression of neuronal nitric oxide synthase and adrenomedullin in human neuroblastoma using real-time PCR. Dötsch, J., Harmjanz, A., Christiansen, H., Hänze, J., Lampert, F., Rascher, W. Int. J. Cancer (2000) [Pubmed]
  4. Glyceraldehyde 3-phosphate dehydrogenase is a novel autoantigen leading autoimmune responses to proliferating cell nuclear antigen multiprotein complexes in lupus patients. Takasaki, Y., Kaneda, K., Matsushita, M., Yamada, H., Nawata, M., Matsudaira, R., Asano, M., Mineki, R., Shindo, N., Hashimoto, H. Int. Immunol. (2004) [Pubmed]
  5. Involvement of glyceraldehyde-3-phosphate dehydrogenase in tumor necrosis factor-related apoptosis-inducing ligand-mediated death of thyroid cancer cells. Du, Z.X., Wang, H.Q., Zhang, H.Y., Gao, D.X. Endocrinology (2007) [Pubmed]
  6. Subcellular alteration of glyceraldehyde-3-phosphate dehydrogenase in Alzheimer's disease fibroblasts. Mazzola, J.L., Sirover, M.A. J. Neurosci. Res. (2003) [Pubmed]
  7. Quantitative DNA perturbations of p53 in endometriosis: analysis of American and Icelandic cases. Gylfason, J.T., Dang, D., Petursdottir, V., Benediktsdottir, K.R., Geirsson, R.T., Poindexter, A., Mitchell-Leef, D., Buster, J.E., Carson, S.A., Simpson, J.L., Bischoff, F.Z. Fertil. Steril. (2005) [Pubmed]
  8. Applicability of the induced-fit model to glyceraldehyde-3-phosphate dehydrogenase from sturgeon muscle. Study of the binding of oxidized nicotinamide adenine dinucleotide and nicotinamide 8-bromoadenine dinucleotide. Branlant, G., Eiler, B., Biellmann, J.F., Lutz, H.P., Luisi, P.L. Biochemistry (1983) [Pubmed]
  9. S phase activation of the histone H2B promoter by OCA-S, a coactivator complex that contains GAPDH as a key component. Zheng, L., Roeder, R.G., Luo, Y. Cell (2003) [Pubmed]
  10. Evidence in favor of the symbiotic origin of chloroplasts: primary structure and evolution of tobacco glyceraldehyde-3-phosphate dehydrogenases. Shih, M.C., Lazar, G., Goodman, H.M. Cell (1986) [Pubmed]
  11. Formaldehyde-induced hemolysis during chronic hemodialysis. Orringer, E.P., Mattern, W.D. N. Engl. J. Med. (1976) [Pubmed]
  12. Hepatocellular glycogenosis and related pattern of enzymatic changes during hepatocarcinogenesis. Bannasch, P., Hacker, H.J., Klimek, F., Mayer, D. Adv. Enzyme Regul. (1984) [Pubmed]
  13. Glycolaldehyde induces apoptosis in a human breast cancer cell line. Al-Maghrebi, M.A., Al-Mulla, F., Benov, L.T. Arch. Biochem. Biophys. (2003) [Pubmed]
  14. A novel CRM1-mediated nuclear export signal governs nuclear accumulation of glyceraldehyde-3-phosphate dehydrogenase following genotoxic stress. Brown, V.M., Krynetski, E.Y., Krynetskaia, N.F., Grieger, D., Mukatira, S.T., Murti, K.G., Slaughter, C.A., Park, H.W., Evans, W.E. J. Biol. Chem. (2004) [Pubmed]
  15. A novel protein complex distinct from mismatch repair binds thioguanylated DNA. Krynetski, E.Y., Krynetskaia, N.F., Gallo, A.E., Murti, K.G., Evans, W.E. Mol. Pharmacol. (2001) [Pubmed]
  16. Mutant huntingtin: nuclear translocation and cytotoxicity mediated by GAPDH. Bae, B.I., Hara, M.R., Cascio, M.B., Wellington, C.L., Hayden, M.R., Ross, C.A., Ha, H.C., Li, X.J., Snyder, S.H., Sawa, A. Proc. Natl. Acad. Sci. U.S.A. (2006) [Pubmed]
  17. Vitamin D is a prooxidant in breast cancer cells. Koren, R., Hadari-Naor, I., Zuck, E., Rotem, C., Liberman, U.A., Ravid, A. Cancer Res. (2001) [Pubmed]
  18. Glyceraldehyde-3-phosphate dehydrogenase selectively binds AU-rich RNA in the NAD(+)-binding region (Rossmann fold). Nagy, E., Rigby, W.F. J. Biol. Chem. (1995) [Pubmed]
  19. Membrane-bound ATP fuels the Na/K pump. Studies on membrane-bound glycolytic enzymes on inside-out vesicles from human red cell membranes. Mercer, R.W., Dunham, P.B. J. Gen. Physiol. (1981) [Pubmed]
  20. Compartment-specific isoforms of TPI and GAPDH are imported into diatom mitochondria as a fusion protein: evidence in favor of a mitochondrial origin of the eukaryotic glycolytic pathway. Liaud, M.F., Lichtlé, C., Apt, K., Martin, W., Cerff, R. Mol. Biol. Evol. (2000) [Pubmed]
  21. Spinocerebellar ataxia type-1 and spinobulbar muscular atrophy gene products interact with glyceraldehyde-3-phosphate dehydrogenase. Koshy, B., Matilla, T., Burright, E.N., Merry, D.E., Fischbeck, K.H., Orr, H.T., Zoghbi, H.Y. Hum. Mol. Genet. (1996) [Pubmed]
  22. Rapid shortening of telomere length in response to ceramide involves the inhibition of telomere binding activity of nuclear glyceraldehyde-3-phosphate dehydrogenase. Sundararaj, K.P., Wood, R.E., Ponnusamy, S., Salas, A.M., Szulc, Z., Bielawska, A., Obeid, L.M., Hannun, Y.A., Ogretmen, B. J. Biol. Chem. (2004) [Pubmed]
  23. Glyceraldehyde 3-phosphate dehydrogenase serves as an accessory protein of the cardiac sarcolemmal K(ATP) channel. Jovanović, S., Du, Q., Crawford, R.M., Budas, G.R., Stagljar, I., Jovanović, A. EMBO Rep. (2005) [Pubmed]
  24. Down-regulation of the DNA-repair endonuclease 8-oxo-guanine DNA glycosylase 1 (hOGG1) by sodium dichromate in cultured human A549 lung carcinoma cells. Hodges, N.J., Chipman, J.K. Carcinogenesis (2002) [Pubmed]
  25. Glyceraldehyde-3-phosphate dehydrogenase enhances transcriptional activity of androgen receptor in prostate cancer cells. Harada, N., Yasunaga, R., Higashimura, Y., Yamaji, R., Fujimoto, K., Moss, J., Inui, H., Nakano, Y. J. Biol. Chem. (2007) [Pubmed]
  26. The active site cysteine of the proapoptotic protein glyceraldehyde-3-phosphate dehydrogenase is essential in oxidative stress-induced aggregation and cell death. Nakajima, H., Amano, W., Fujita, A., Fukuhara, A., Azuma, Y.T., Hata, F., Inui, T., Takeuchi, T. J. Biol. Chem. (2007) [Pubmed]
  27. T-13910 DNA variant associated with lactase persistence interacts with Oct-1 and stimulates lactase promoter activity in vitro. Lewinsky, R.H., Jensen, T.G., Møller, J., Stensballe, A., Olsen, J., Troelsen, J.T. Hum. Mol. Genet. (2005) [Pubmed]
  28. Enhancement of hammerhead ribozyme catalysis by glyceraldehyde-3-phosphate dehydrogenase. Sioud, M., Jespersen, L. J. Mol. Biol. (1996) [Pubmed]
  29. Human glyceraldehyde-3-phosphate dehydrogenase plays a direct role in reactivating oxidized forms of the DNA repair enzyme APE1. Azam, S., Jouvet, N., Jilani, A., Vongsamphanh, R., Yang, X., Yang, S., Ramotar, D. J. Biol. Chem. (2008) [Pubmed]
  30. An improved assay for UDPglucose pyrophosphorylase and other enzymes that have nucleotide products. Duggleby, R.G., Peng, H.L., Chang, H.Y. Experientia (1996) [Pubmed]
  31. The non-phosphorylating glyceraldehyde-3-phosphate dehydrogenase: biochemistry, structure, occurrence and evolution. Habenicht, A. Biol. Chem. (1997) [Pubmed]
  32. Thioredoxin, a regulator of gene expression. Kontou, M., Will, R.D., Adelfalk, C., Wittig, R., Poustka, A., Hirsch-Kauffmann, M., Schweiger, M. Oncogene (2004) [Pubmed]
  33. Hox expression in AML identifies a distinct subset of patients with intermediate cytogenetics. Roche, J., Zeng, C., Barón, A., Gadgil, S., Gemmill, R.M., Tigaud, I., Thomas, X., Drabkin, H.A. Leukemia (2004) [Pubmed]
  34. Thioredoxin-dependent regulation of photosynthetic glyceraldehyde-3-phosphate dehydrogenase: autonomous vs. CP12-dependent mechanisms. Trost, P., Fermani, S., Marri, L., Zaffagnini, M., Falini, G., Scagliarini, S., Pupillo, P., Sparla, F. Photosyn. Res. (2006) [Pubmed]
  35. Claudin-1, -3 and -4 proteins and mRNA expression in benign and malignant breast lesions: a research study. Tokés, A.M., Kulka, J., Paku, S., Szik, A., Páska, C., Novák, P.K., Szilák, L., Kiss, A., Bögi, K., Schaff, Z. Breast Cancer Res. (2005) [Pubmed]
  36. Adrenomedullin, calcitonin gene-related peptide and their receptors: evidence for a decreased placental mRNA content in preeclampsia and HELLP syndrome. Knerr, I., Dachert, C., Beinder, E., Metzler, M., Dötsch, J., Repp, R., Rascher, W. Eur. J. Obstet. Gynecol. Reprod. Biol. (2002) [Pubmed]
  37. Huntingtin and DRPLA proteins selectively interact with the enzyme GAPDH. Burke, J.R., Enghild, J.J., Martin, M.E., Jou, Y.S., Myers, R.M., Roses, A.D., Vance, J.M., Strittmatter, W.J. Nat. Med. (1996) [Pubmed]
  38. Triosephosphate isomerase- and glyceraldehyde-3-phosphate dehydrogenase-reactive autoantibodies in the cerebrospinal fluid of patients with multiple sclerosis. Kolln, J., Ren, H.M., Da, R.R., Zhang, Y., Spillner, E., Olek, M., Hermanowicz, N., Hilgenberg, L.G., Smith, M.A., van den Noort, S., Qin, Y. J. Immunol. (2006) [Pubmed]
  39. Ketoconazole and miconazole are antagonists of the human glucocorticoid receptor: consequences on the expression and function of the constitutive androstane receptor and the pregnane X receptor. Duret, C., Daujat-Chavanieu, M., Pascussi, J.M., Pichard-Garcia, L., Balaguer, P., Fabre, J.M., Vilarem, M.J., Maurel, P., Gerbal-Chaloin, S. Mol. Pharmacol. (2006) [Pubmed]
  40. Cell cycle regulation of the glyceraldehyde-3-phosphate dehydrogenase/uracil DNA glycosylase gene in normal human cells. Mansur, N.R., Meyer-Siegler, K., Wurzer, J.C., Sirover, M.A. Nucleic Acids Res. (1993) [Pubmed]
  41. Validity of messenger RNA expression analyses of human saliva. Kumar, S.V., Hurteau, G.J., Spivack, S.D. Clin. Cancer Res. (2006) [Pubmed]
WikiGenes - Universities