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Gene Review

TPI1  -  triosephosphate isomerase 1

Homo sapiens

Synonyms: HEL-S-49, TIM, TPI, TPID, Triose-phosphate isomerase, ...
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Disease relevance of TPI1


Psychiatry related information on TPI1


High impact information on TPI1

  • Separate translocases in the mitochondrial outer membrane (TOM complex) and in the inner membrane (TIM complex) facilitate recognition of preproteins and transport across the two membranes [7].
  • These T cell subsets are primarily differentiated on the basis of the cytokines that they produce, however, we have identified a novel gene family called TIM (T cell, immunoglobulin, mucin domain-containing molecules), whose members are differentially expressed on Th1 and Th2 cells [8].
  • Genomic association of the TIM family and polymorphisms in both Tim-1 and Tim-3 in different immune-mediated diseases suggest that the family may have an important role in regulating immunity, both in terms of normal immune responses and in diseases like autoimmunity and asthma [8].
  • These additional TPI gene introns are also required for the efficient removal of intron 6 [9].
  • Protein translocation into mitochondria: the role of TIM complexes [10].

Chemical compound and disease context of TPI1


Biological context of TPI1

  • The findings suggest that TPI and GAPDH may be candidate Ags for an autoimmune response to neurons and axons in MS [1].
  • Phylogenetic analyses show that mitochondrial GAPDH and its N-terminal TPI fusion branch deeply within their respective eukaryotic protein phylogenies, suggesting that diatom mitochondria may have retained an ancestral state of glycolytic compartmentation that existed at the onset of mitochondrial symbiosis [16].
  • The difference in K(m) is indicative of the difference in the active site of the human and M. tuberculosis TPI, which can be exploited for drug designing specifically targeting M. tuberculosis TPI [2].
  • Triosephosphate isomerase (TPI), one of the key enzymes of the glycolytic pathway, is an attractive drug target against Mycobacterium tuberculosis as glycolysis provides the majority of the organism's energy requirements inside macrophages [2].
  • Mitochondrial and Tpi genealogies are consistent with reciprocal monophyly, whereas sympatric populations of the species in Panama share identical or similar Mpi and Ci haplotypes, giving rise to genealogical polyphyly at the species level despite evidence for rapid sequence divergence at these genes between geographic races of H. melpomene [17].

Anatomical context of TPI1

  • The efficacy order of TPI binding to microtubules is propositus > brother without neurological disorder > normal control [18].
  • Our present studies with purified TPI and hemolysates revealed the binding of TPI, and the binding of human wild-type and mutant TPIs in hemolysate, to the red cell membrane, and the interference of binding with other hemolysate proteins [18].
  • The interaction of cofilin with triose-phosphate isomerase as well as Na,K-ATPase was confirmed by immunoprecipitation and confocal microscopy in HeLa cells [19].
  • 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 [16].
  • 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 [16].

Associations of TPI1 with chemical compounds

  • Importantly, the apparent K(m) value of M. tuberculosis rTPI for the substrate glyceraldehyde-3-phosphate is 84 muM which is sevenfold higher than the value reported for human TPI [2].
  • Although this substitution conserves the overall charge of amino acid-104, the x-ray crystal structure of chicken TPI indicates that the loss of a side-chain methylene group (-CH2CH2COO- ---- -CH2COO-) is sufficient to disrupt the counterbalancing of charges that normally exists within a hydrophobic pocket of the native enzyme [4].
  • The glutamate-to-aspartate substitution results in a thermolabile enzyme as demonstrated by assays of TPI activity in cultured fibroblasts of each patient and cultured Chinese hamster ovary (CHO) cells that were stably transformed with the mutant alleles [4].
  • Reduction of this material using phosphoglycerate kinase/ATP, glyceraldehyde-3-phosphate dehydrogenase/NADH, triose-phosphate isomerase, and glycerol-phosphate dehydrogenase/NADH produces glycerol 3-[18O]phosphorothioate, which is subjected to ring closure using diethylphosphorochloridate [20].
  • Two hTIM mutants were produced, in which a glutamine residue was substituted for either Met14 or Arg98, both of which are interface residuces [21].

Physical interactions of TPI1


Other interactions of TPI1

  • Both GAPD and TPI1 do not have conserved E boxes but are induced and bound by Myc through regions with noncanonical E boxes [23].
  • Two scFv-Abs generated from the CSF and from lesions of a MS brain showed immunoreactivity to TPI and GAPDH, respectively [1].
  • Furthermore, the occurrence of autoantibodies against Tim and MnSOD was evaluated by ELISA in an additional 40 LSC patients, 30 other types of cancer (OTC) patients, and 50 noncancer controls (NC) [3].
  • The gene for the peroxisomal targeting signal import receptor (PXR1) is located on human chromosome 12p13, flanked by TPI1 and D12S1089 [24].
  • Identification of the origin of a 22p+ chromosome by triplex dosage effect of LDH B, GAPHD, TPI and ENO2 [25].

Analytical, diagnostic and therapeutic context of TPI1


  1. 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]
  2. Biochemical and functional characterization of triosephosphate isomerase from Mycobacterium tuberculosis H37Rv. Mathur, D., Malik, G., Garg, L.C. FEMS Microbiol. Lett. (2006) [Pubmed]
  3. Identification of tumor antigens in human lung squamous carcinoma by serological proteome analysis. Yang, F., Xiao, Z.Q., Zhang, X.Z., Li, C., Zhang, P.F., Li, M.Y., Chen, Y., Zhu, G.Q., Sun, Y., Liu, Y.F., Chen, Z.C. J. Proteome Res. (2007) [Pubmed]
  4. Human triose-phosphate isomerase deficiency: a single amino acid substitution results in a thermolabile enzyme. Daar, I.O., Artymiuk, P.J., Phillips, D.C., Maquat, L.E. Proc. Natl. Acad. Sci. U.S.A. (1986) [Pubmed]
  5. Myopathy with altered mitochondria due to a triosephosphate isomerase (TPI) deficiency. Bardosi, A., Eber, S.W., Hendrys, M., Pekrun, A. Acta Neuropathol. (1990) [Pubmed]
  6. Glycolytic enzymes from human autoptic brain cortex: normal aged and demented cases. Iwangoff, P., Armbruster, R., Enz, A., Meier-Ruge, W. Mech. Ageing Dev. (1980) [Pubmed]
  7. Protein import into mitochondria. Neupert, W. Annu. Rev. Biochem. (1997) [Pubmed]
  8. TIM Family of Genes in Immunity and Tolerance. Kuchroo, V.K., Meyers, J.H., Umetsu, D.T., Dekruyff, R.H. Adv. Immunol. (2006) [Pubmed]
  9. Upstream introns influence the efficiency of final intron removal and RNA 3'-end formation. Nesic, D., Maquat, L.E. Genes Dev. (1994) [Pubmed]
  10. Protein translocation into mitochondria: the role of TIM complexes. Bauer, M.F., Hofmann, S., Neupert, W., Brunner, M. Trends Cell Biol. (2000) [Pubmed]
  11. Human triosephosphate isomerase deficiency resulting from mutation of Phe-240. Chang, M.L., Artymiuk, P.J., Wu, X., Hollán, S., Lammi, A., Maquat, L.E. Am. J. Hum. Genet. (1993) [Pubmed]
  12. The functional and immunological significance of some schistosome surface molecules. Wright, M.D., Davern, K.M., Mitchell, G.F. Parasitol. Today (Regul. Ed.) (1991) [Pubmed]
  13. Adverse effects of dopamine potentiation by long-term treatment with selegiline. Hollán, S., Vécsei, L., Magyar, K. Mov. Disord. (2004) [Pubmed]
  14. A comparative study of biochemical and immunological properties of triosephosphate isomerase from Taenia solium and Sus scrofa. Jiménez, L., Fernández-Velasco, D.A., Willms, K., Landa, A. J. Parasitol. (2003) [Pubmed]
  15. Local encoding of computationally designed enzyme activity. Allert, M., Dwyer, M.A., Hellinga, H.W. J. Mol. Biol. (2007) [Pubmed]
  16. 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]
  17. Polyphyly and gene flow between non-sibling Heliconius species. Bull, V., Beltrán, M., Jiggins, C.D., McMillan, W.O., Bermingham, E., Mallet, J. BMC Biol. (2006) [Pubmed]
  18. Enhanced association of mutant triosephosphate isomerase to red cell membranes and to brain microtubules. Orosz, F., Wágner, G., Liliom, K., Kovács, J., Baróti, K., Horányi, M., Farkas, T., Hollán, S., Ovádi, J. Proc. Natl. Acad. Sci. U.S.A. (2000) [Pubmed]
  19. Interaction of cofilin with triose-phosphate isomerase contributes glycolytic fuel for Na,K-ATPase via Rho-mediated signaling pathway. Jung, J., Yoon, T., Choi, E.C., Lee, K. J. Biol. Chem. (2002) [Pubmed]
  20. The stereochemical course of the ribulose-5-phosphate kinase-catalyzed reaction. Miziorko, H.M., Eckstein, F. J. Biol. Chem. (1984) [Pubmed]
  21. Three hTIM mutants that provide new insights on why TIM is a dimer. Mainfroid, V., Terpstra, P., Beauregard, M., Frère, J.M., Mande, S.C., Hol, W.G., Martial, J.A., Goraj, K. J. Mol. Biol. (1996) [Pubmed]
  22. Structural determinants for ligand binding and catalysis of triosephosphate isomerase. Kursula, I., Partanen, S., Lambeir, A.M., Antonov, D.M., Augustyns, K., Wierenga, R.K. Eur. J. Biochem. (2001) [Pubmed]
  23. Evaluation of myc E-box phylogenetic footprints in glycolytic genes by chromatin immunoprecipitation assays. Kim, J.W., Zeller, K.I., Wang, Y., Jegga, A.G., Aronow, B.J., O'Donnell, K.A., Dang, C.V. Mol. Cell. Biol. (2004) [Pubmed]
  24. The gene for the peroxisomal targeting signal import receptor (PXR1) is located on human chromosome 12p13, flanked by TPI1 and D12S1089. Marynen, P., Fransen, M., Raeymaekers, P., Mannaerts, G.P., Van Veldhoven, P.P. Genomics (1995) [Pubmed]
  25. Identification of the origin of a 22p+ chromosome by triplex dosage effect of LDH B, GAPHD, TPI and ENO2. Dallapiccola, B., Brinchi, V., Magnani, M., Dacha, M. Ann. Genet. (1980) [Pubmed]
  26. Structure of a high-resolution crystal form of human triosephosphate isomerase: improvement of crystals using the gel-tube method. Kinoshita, T., Maruki, R., Warizaya, M., Nakajima, H., Nishimura, S. Acta Crystallograph. Sect. F Struct. Biol. Cryst. Commun. (2005) [Pubmed]
  27. Enzyme-enzyme interaction in the chloroplast: glyceraldehyde-3-phosphate dehydrogenase, triose phosphate isomerase and aldolase. Anderson, L.E., Goldhaber-Gordon, I.M., Li, D., Tang, X.Y., Xiang, M., Prakash, N. Planta (1995) [Pubmed]
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