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Gene Review

Tpi1  -  triosephosphate isomerase 1

Mus musculus

Synonyms: AI255506, TIM, Tpi, Tpi-1, Triose-phosphate isomerase, ...
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Disease relevance of Tpi1


High impact information on Tpi1

  • CD22 signaling is mediated via interactions with a number of kinases and phosphatases that bind the cytoplasmic domain through phosphorylated tyrosine residues located within consensus TAM and TIM motifs [6].
  • (i) A suppressor tRNA, which acts in trans to suppress an amber nonsense codon within TPI mRNA, and (ii) a hairpin structure in the 5' untranslated region of TPI mRNA, which acts exclusively in cis to inhibit initiation of TPI mRNA translation, were found, individually, and to a greater extent, together, to abrogate the decrease in mRNA [7].
  • Evidence to implicate translation by ribosomes in the mechanism by which nonsense codons reduce the nuclear level of human triosephosphate isomerase mRNA [7].
  • The abundance of the mRNA for human triosephosphate isomerase (TPI) is decreased to 20-30% of normal by frameshift and nonsense mutations that prematurely terminate translation within the first three-quarters of the reading frame [7].
  • TPI pre-mRNA harbors six introns that are constitutively removed by splicing [8].

Chemical compound and disease context of Tpi1

  • RESULTS: After 7 to 14 days in co-culture with UMR106 osteoblast-like cells in the presence of 1,25-dihydroxy vitamin D3, only cells of the TIM population differentiated into osteoclast-like cells (nonspecific esterase-negative: tartrate-resistant acid phosphatase-positive) capable of extensive lacunar bone resorption [9].
  • When cells expressing the recombinant TPI protein with histidine tag were exposed to hypoxia and the TPI protein was affinity-purified, the catalytic activity (specific activity) of the TPI protein purified from hypoxic cells was substantially lower than that obtained from normoxic cells [10].
  • The induction of TPI gene expression by hypoxia was suppressed by (1) a chelator of intracellular Ca(2+), (2) a blocker of non-selective cation channels, (3) a blocker of Na(+)/Ca(2+) exchangers, (4) an inhibitor of Ca(2+)/calmodulin-dependent protein kinases, and (5) an inhibitor of c-jun/AP-1 activation [10].

Biological context of Tpi1


Anatomical context of Tpi1

  • Assignment of a Mus musculus gene for triosephosphate isomerase to chromosome 6 and for glyoxalase-I to chromosome 17 using somatic cell hybrids [15].
  • The dependence of TPI RNA 3'-end formation on splicing may reflect the suboptimal strengths of the corresponding regulatory sequences and may function to ensure that TPI pre-mRNA is not released from the chromatin template until it has formed a complex with spliceosomes [8].
  • In cultured cells, little if any mRNA accumulates from an intronless version of the human gene for triosephosphate isomerase (TPI), a gene that normally contains six introns [16].
  • Tim-3, a member of the T cell Ig mucin (TIM) family regulates effector Th1 responses [17].
  • These Ag as well as two 28 kDa proteins, triosephosphate isomerase and glutathione S-transferase, in purified native or recombinant form or as a synthetic peptide, stimulated lymphocyte proliferation [18].

Associations of Tpi1 with chemical compounds

  • A mutation resulting in increased triosephosphate isomerase (TPI) activity in blood was recovered in offspring of procarbazine hydrochloride-treated male mice [12].
  • Four heterozygous triosephosphate isomerase (TPI) mutants with approximately 50% reduced activity in blood compared to wild type were detected in offspring of 1-ethyl-1-nitrosourea treated male mice [1].
  • However, the step in TPI RNA metabolism that is altered was not defined, and the use of actinomycin D, in affecting all polymerase II-transcribed genes, could result in artifactual conclusions [19].
  • This study substantiates that the five Ag, paramyosin, heat shock protein 70, triosephosphate isomerase, glutathione S-transferase, and the integral membrane protein Sm23, are important candidates for a defined antischistosomal vaccine [18].
  • Oxidation of purified enolase or TPI via Fenton chemistry led to a 17 or 23% loss of activity, respectively, confirming that a loss of activity was the consequence of oxidation [20].

Other interactions of Tpi1


Analytical, diagnostic and therapeutic context of Tpi1

  • To examine the consequences of GAPDH inhibition upon neuronal survival, we exposed murine neocortical cell cultures to the inhibitor of GAPDH and triosephosphate isomerase, alpha-monochlorohydrin [24].
  • Exons of the TPI gene from control mice and heterozygous mutant mice were PCR amplified and sequenced as necessary to determine the molecular lesion in the mutant alleles [25].
  • Only one mab out of fifteen cross-reacted in direct ELISA binding to all amylases and triose phosphate isomerase [26].


  1. Characterization of triosephosphate isomerase mutants with reduced enzyme activity in Mus musculus. Merkle, S., Pretsch, W. Genetics (1989) [Pubmed]
  2. Identification and applications of repetitive probes for gene mapping in the mouse. Siracusa, L.D., Jenkins, N.A., Copeland, N.G. Genetics (1991) [Pubmed]
  3. Genetic transmission of Moloney leukemia virus: mapping of the chromosomal integration site. Doehmer, J., Breindl, M., Willecke, K., Jaenisch, R. Haematology and blood transfusion. (1979) [Pubmed]
  4. Comparative gene expression profile of mouse carotid body and adrenal medulla under physiological hypoxia. Ganfornina, M.D., Pérez-García, M.T., Gutiérrez, G., Miguel-Velado, E., López-López, J.R., Marín, A., Sánchez, D., González, C. J. Physiol. (Lond.) (2005) [Pubmed]
  5. Tumoricidal alveolar macrophage and tumor infiltrating macrophage cell lines. Palleroni, A.V., Varesio, L., Wright, R.B., Brunda, M.J. Int. J. Cancer (1991) [Pubmed]
  6. CD22, a B lymphocyte-specific adhesion molecule that regulates antigen receptor signaling. Tedder, T.F., Tuscano, J., Sato, S., Kehrl, J.H. Annu. Rev. Immunol. (1997) [Pubmed]
  7. Evidence to implicate translation by ribosomes in the mechanism by which nonsense codons reduce the nuclear level of human triosephosphate isomerase mRNA. Belgrader, P., Cheng, J., Maquat, L.E. Proc. Natl. Acad. Sci. U.S.A. (1993) [Pubmed]
  8. Lack of an effect of the efficiency of RNA 3'-end formation on the efficiency of removal of either the final or the penultimate intron in intact cells. Nesic, D., Zhang, J., Maquat, L.E. Mol. Cell. Biol. (1995) [Pubmed]
  9. Cellular and hormonal mechanisms associated with malignant bone resorption. Quinn, J.M., Matsumura, Y., Tarin, D., McGee, J.O., Athanasou, N.A. Lab. Invest. (1994) [Pubmed]
  10. Hypoxic up-regulation of triosephosphate isomerase expression in mouse brain capillary endothelial cells. Yamaji, R., Fujita, K., Nakanishi, I., Nagao, K., Naito, M., Tsuruo, T., Inui, H., Nakano, Y. Arch. Biochem. Biophys. (2004) [Pubmed]
  11. Tpi-1 and Gapd are linked very closely on mouse chromosome 6. Pretsch, W., Neuhäuser-Klaus, A., Merkle, S. Genet. Res. (1991) [Pubmed]
  12. A mutation resulting in increased triosephosphate isomerase activity in Mus musculus. Merkle, S., Reitmeir, P., Pretsch, W. Genet. Res. (1991) [Pubmed]
  13. Nucleotide sequence of murine triosephosphate isomerase cDNA. Cheng, J., Mielnicki, L.M., Pruitt, S.C., Maquat, L.E. Nucleic Acids Res. (1990) [Pubmed]
  14. Mutation in intron 6 of the hamster Mitf gene leads to skipping of the subsequent exon and creates a novel animal model for the human Waardenburg syndrome type II. Graw, J., Pretsch, W., Löster, J. Genetics (2003) [Pubmed]
  15. Assignment of a Mus musculus gene for triosephosphate isomerase to chromosome 6 and for glyoxalase-I to chromosome 17 using somatic cell hybrids. Minna, J.D., Bruns, G.A., Krinsky, A.H., Lalley, P.A., Francke, U., Gerald, P.S. Somatic Cell Genet. (1978) [Pubmed]
  16. Sequences within the last intron function in RNA 3'-end formation in cultured cells. Nesic, D., Cheng, J., Maquat, L.E. Mol. Cell. Biol. (1993) [Pubmed]
  17. Preferential Involvement of Tim-3 in the Regulation of Hepatic CD8+ T Cells in Murine Acute Graft-versus-Host Disease. Oikawa, T., Kamimura, Y., Akiba, H., Yagita, H., Okumura, K., Takahashi, H., Zeniya, M., Tajiri, H., Azuma, M. J. Immunol. (2006) [Pubmed]
  18. Candidate vaccine antigens that stimulate the cellular immune response of mice vaccinated with irradiated cercariae of Schistosoma mansoni. Richter, D., Reynolds, S.R., Harn, D.A. J. Immunol. (1993) [Pubmed]
  19. Nonsense codons can reduce the abundance of nuclear mRNA without affecting the abundance of pre-mRNA or the half-life of cytoplasmic mRNA. Cheng, J., Maquat, L.E. Mol. Cell. Biol. (1993) [Pubmed]
  20. Redox proteomic identification of oxidized cardiac proteins in Adriamycin-treated mice. Chen, Y., Daosukho, C., Opii, W.O., Turner, D.M., Pierce, W.M., Klein, J.B., Vore, M., Butterfield, D.A., St Clair, D.K. Free Radic. Biol. Med. (2006) [Pubmed]
  21. The crystal structure of a novel mammalian lectin, Ym1, suggests a saccharide binding site. Sun, Y.J., Chang, N.C., Hung, S.I., Chang, A.C., Chou, C.C., Hsiao, C.D. J. Biol. Chem. (2001) [Pubmed]
  22. Influence of age and caloric restriction on liver glycolytic enzyme activities and metabolite concentrations in mice. Hagopian, K., Ramsey, J.J., Weindruch, R. Exp. Gerontol. (2003) [Pubmed]
  23. Genetical and biochemical studies of a dominant cataract mutant in mice. Graw, J., Kratochvilova, J., Summer, K.H. Exp. Eye Res. (1984) [Pubmed]
  24. Neuronal death in cultured murine cortical cells is induced by inhibition of GAPDH and triosephosphate isomerase. Sheline, C.T., Choi, D.W. Neurobiol. Dis. (1998) [Pubmed]
  25. Molecular analysis of four ENU induced triosephosphate isomerase null mutants in Mus musculus. Zingg, B.C., Pretsch, W., Mohrenweiser, H.W. Mutat. Res. (1995) [Pubmed]
  26. Antigen specificity and cross-reactivity of fifteen monoclonal antibodies against porcine pancreatic alpha-amylase II and its AB and C domains. Fueri, J., Fueri, C., Ferrey, G., Chaix, J.C., Marchis-Mouren, G. Hybridoma (1992) [Pubmed]
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