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Gene Review

GPI  -  glucose-6-phosphate isomerase

Homo sapiens

Synonyms: AMF, Autocrine motility factor, GNPI, Glucose-6-phosphate isomerase, NLK, ...
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Disease relevance of GPI


Psychiatry related information on GPI


High impact information on GPI


Chemical compound and disease context of GPI


Biological context of GPI

  • We propose that GPI-anti-GPI complexes on articular surfaces initiate an inflammatory cascade via the alternative complement pathway, which is unbridled because the cartilage surface lacks the usual cellular inhibitors [17].
  • Strikingly, the red cell GPI activity in this patient was higher than that found in a second patient expressing the same GPI variant, with a more severe clinical phenotype [2].
  • Subsequent DNA sequence analysis revealed a novel homozygous 921C to G mutation in the GPI gene sequence, predicting a Phe307 to Leu replacement [2].
  • G6PI-induced arthritis demonstrates for the first time the induction of organ-specific disease by systemic autoimmunity in genetically unaltered mice [3].
  • MMP-3 inhibition abolished the PGI/AMF-induced cell motility [4].

Anatomical context of GPI


Associations of GPI with chemical compounds


Physical interactions of GPI

  • Synovial fluid samples from RA patients showed a significantly higher level of binding to recombinant GPI proteins than samples from OA patients [27].
  • Peptide T analogs or synthetic cogeners of Neuroleukin proposed to bind the CD4 determinant involved in gp120 binding had no competitive displacement of native gp120 binding as assessed by two independent methods that measure gp120 interaction with CD4 [28].

Regulatory relationships of GPI


Other interactions of GPI

  • CONCLUSION: Our findings suggest that GPI is not a specific autoantigen in RA [32].
  • Induction of hepatoma cells migration by phosphoglucose isomerase/autocrine motility factor through the upregulation of matrix metalloproteinase-3 [4].
  • This study suggests that the metabolic consequences of a combined deficiency of GPI and G6PD might be responsible for a different clinical outcome than predicted for either defect in isolation [2].
  • There was father-to-son transmission of PGI, PGM-1, peptidase C, 6PGD, 2,3-DPGAM, NADP-ICD, and acid phosphatase variants, suggesting that these loci are autosomal as in man [33].
  • The elevated titers of anti-GRP78 and anti-PGI IgG observed at the beginning of treatment decreased significantly during therapy, whereas those of anti-LDH, anti-FN, and anti-actin IgG remained unchanged [34].

Analytical, diagnostic and therapeutic context of GPI


  1. Autoantibodies in juvenile idiopathic arthritis: glucose-6-phosphate isomerase is not a specific target. Schepp, C.P., Dannecker, L., Haug, M., Kümmerle-Deschner, J., Beck, H., Kötter, I., Holzer, U., Dannecker, G.E. J. Rheumatol. (2004) [Pubmed]
  2. Combined glucose-6-phosphate dehydrogenase and glucosephosphate isomerase deficiency can alter clinical outcome. Clarke, J.L., Vulliamy, T.J., Roper, D., Mesbah-Namin, S.A., Wild, B.J., Walker, J.I., Will, A.M., Bolton-Maggs, P.H., Mason, P.J., Layton, D.M. Blood Cells Mol. Dis. (2003) [Pubmed]
  3. Immunization with glucose-6-phosphate isomerase induces T cell-dependent peripheral polyarthritis in genetically unaltered mice. Schubert, D., Maier, B., Morawietz, L., Krenn, V., Kamradt, T. J. Immunol. (2004) [Pubmed]
  4. Induction of hepatoma cells migration by phosphoglucose isomerase/autocrine motility factor through the upregulation of matrix metalloproteinase-3. Yu, F.L., Liao, M.H., Lee, J.W., Shih, W.L. Biochem. Biophys. Res. Commun. (2004) [Pubmed]
  5. The first stable variant of erythrocyte glucose-phosphate isomerase associated with severe hemolytic anemia. Zanella, A., Izzo, C., Rebulla, P., Perroni, L., Mariani, M., Canestri, G., Sansone, G., Sirchia, G. Am. J. Hematol. (1980) [Pubmed]
  6. Genetic relationships among phlebotomine sand flies (Diptera: Psychodidae) in the verrucarum species group. Kreutzer, R.D., Palau, M.T., Morales, A., Ferro, C., Feliciangeli, D., Young, D.G. J. Med. Entomol. (1990) [Pubmed]
  7. Functional interaction and partial homology between human immunodeficiency virus and neuroleukin. Lee, M.R., Ho, D.D., Gurney, M.E. Science (1987) [Pubmed]
  8. Impaired brain glucose metabolism in patients with Down syndrome. Labudova, O., Cairns, N., Kitzmüller, E., Lubec, G. J. Neural Transm. Suppl. (1999) [Pubmed]
  9. 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]
  10. Glucose phosphate isomerase deficiency as a cause of hydrops fetalis. Ravindranath, Y., Paglia, D.E., Warrier, I., Valentine, W., Nakatani, M., Brockway, R.A. N. Engl. J. Med. (1987) [Pubmed]
  11. Localization of the malignant hyperthermia susceptibility locus to human chromosome 19q12-13.2. McCarthy, T.V., Healy, J.M., Heffron, J.J., Lehane, M., Deufel, T., Lehmann-Horn, F., Farrall, M., Johnson, K. Nature (1990) [Pubmed]
  12. Mouse glucose-6-phosphate isomerase and neuroleukin have identical 3' sequences. Faik, P., Walker, J.I., Redmill, A.A., Morgan, M.J. Nature (1988) [Pubmed]
  13. Autocrine motility factor enhances hepatoma cell invasion across the basement membrane through activation of beta1 integrins. Torimura, T., Ueno, T., Kin, M., Harada, R., Nakamura, T., Kawaguchi, T., Harada, M., Kumashiro, R., Watanabe, H., Avraham, R., Sata, M. Hepatology (2001) [Pubmed]
  14. Inhibitory effect of mannose on erythrocyte defense against oxidants. Lachant, N.A., Zerez, C.R. Biochim. Biophys. Acta (1988) [Pubmed]
  15. Inhibition of poly(ADP-ribose) polymerase prevents irinotecan-induced intestinal damage and enhances irinotecan/temozolomide efficacy against colon carcinoma. Tentori, L., Leonetti, C., Scarsella, M., Muzi, A., Mazzon, E., Vergati, M., Forini, O., Lapidus, R., Xu, W., Dorio, A.S., Zhang, J., Cuzzocrea, S., Graziani, G. FASEB J. (2006) [Pubmed]
  16. Enzyme abnormalities of patients with acquired immunodeficiency syndrome. Huang, C.M., Ruddel, M., Elin, R.J. Clin. Chem. (1988) [Pubmed]
  17. How antibodies to a ubiquitous cytoplasmic enzyme may provoke joint-specific autoimmune disease. Matsumoto, I., Maccioni, M., Lee, D.M., Maurice, M., Simmons, B., Brenner, M., Mathis, D., Benoist, C. Nat. Immunol. (2002) [Pubmed]
  18. Combined glucose phosphate isomerase and glucose-6-phosphate dehydrogenase deficiency of erythrocytes. Steiman, I., Kaufman, S., Zaidman, J.L., Leiba, H. Isr. J. Med. Sci. (1978) [Pubmed]
  19. Autoantibodies to GPI in rheumatoid arthritis: linkage between an animal model and human disease. Schaller, M., Burton, D.R., Ditzel, H.J. Nat. Immunol. (2001) [Pubmed]
  20. The exploration of joint-specific immunoreactions on immunoglobulins G of anti-glucose-6-phosphate isomerase antibody-positive patients with rheumatoid arthritis. Matsumoto, I., Muraki, Y., Yasukochi, T., Hua, Z., Kori, Y., Hayashi, T., Goto, D., Ito, S., Tsutsumi, A., Ikeda, K., Sumichika, H., Sumida, T. Int. J. Mol. Med. (2005) [Pubmed]
  21. Phosphohexose isomerase/autocrine motility factor/neuroleukin/maturation factor is a multifunctional phosphoprotein. Haga, A., Niinaka, Y., Raz, A. Biochim. Biophys. Acta (2000) [Pubmed]
  22. Accuracy of portein synthesis and in vitro aging. Search for altered enzymes in senescent cultured cells from human livers. Kahn, A., Guillouzo, A., Cottreau, D., Marie, J., Bourel, M., Boivin, P., Dreyfus, J.C. Gerontology. (1977) [Pubmed]
  23. A genetic study among the Lepchas of the Darjeeling area of eastern India. Saha, N., Bhattacharyya, S.P., Mukhopadhyay, B., Bhattacharyya, S.K., Gupta, R., Basu, A. Hum. Hered. (1987) [Pubmed]
  24. Molecular analysis of glucose phosphate isomerase deficiency associated with hereditary hemolytic anemia. Kanno, H., Fujii, H., Hirono, A., Ishida, Y., Ohga, S., Fukumoto, Y., Matsuzawa, K., Ogawa, S., Miwa, S. Blood (1996) [Pubmed]
  25. Down-regulation of phosphoglucose isomerase/autocrine motility factor expression sensitizes human fibrosarcoma cells to oxidative stress leading to cellular senescence. Funasaka, T., Hu, H., Hogan, V., Raz, A. J. Biol. Chem. (2007) [Pubmed]
  26. Raft-dependent endocytosis of autocrine motility factor is phosphatidylinositol 3-kinase-dependent in breast carcinoma cells. Kojic, L.D., Joshi, B., Lajoie, P., Le, P.U., Cox, M.E., Turbin, D.A., Wiseman, S.M., Nabi, I.R. J. Biol. Chem. (2007) [Pubmed]
  27. Detection of antibodies against glucose 6-phosphate isomerase in synovial fluid of rheumatoid arthritis using surface plasmon resonance (BIAcore). Kim, J.Y., Lee, M.H., Jung, K.I., Na, H.Y., Cha, H.S., Ko, E.M., Kim, T.J. Exp. Mol. Med. (2003) [Pubmed]
  28. Characterization of CD4 glycoprotein determinant-HIV envelope protein interactions: perspectives for analog and vaccine development. Farrar, W.L., Harel-Bellan, A., Ferris, D.K. Crit. Rev. Immunol. (1988) [Pubmed]
  29. Association of autoantibodies to glucose-6-phosphate isomerase with extraarticular complications in rheumatoid arthritis. van Gaalen, F.A., Toes, R.E., Ditzel, H.J., Schaller, M., Breedveld, F.C., Verweij, C.L., Huizinga, T.W. Arthritis Rheum. (2004) [Pubmed]
  30. SB202190, a selective inhibitor of p38 mitogen-activated protein kinase, is a powerful regulator of LPS-induced mRNAs in monocytes. Manthey, C.L., Wang, S.W., Kinney, S.D., Yao, Z. J. Leukoc. Biol. (1998) [Pubmed]
  31. Regulation of phosphoglucose isomerase/autocrine motility factor activities by the poly(ADP-ribose) polymerase family-14. Yanagawa, T., Funasaka, T., Tsutsumi, S., Hu, H., Watanabe, H., Raz, A. Cancer Res. (2007) [Pubmed]
  32. Glucose-6-phosphate isomerase is not a specific autoantigen in rheumatoid arthritis. Herve, C.A., Wait, R., Venables, P.J. Rheumatology (Oxford, England) (2003) [Pubmed]
  33. Intraspecific red cell enzyme variation in the pigtailed macaque (Macaca nemestrina). Anderson, J.E., Giblett, E.R. Biochem. Genet. (1975) [Pubmed]
  34. Anti-tumor necrosis factor-alpha therapy augments dipeptidyl peptidase IV activity and decreases autoantibodies to GRP78/BIP and phosphoglucose isomerase in patients with rheumatoid arthritis. Mavropoulos, J.C., Cuchacovich, M., Llanos, C., Aguillón, J.C., Gatica, H., Pizzo, S.V., Gonzalez-Gronow, M. J. Rheumatol. (2005) [Pubmed]
  35. Dynamic visualization of a joint-specific autoimmune response through positron emission tomography. Wipke, B.T., Wang, Z., Kim, J., McCarthy, T.J., Allen, P.M. Nat. Immunol. (2002) [Pubmed]
  36. Autoantibodies to glucose-6-phosphate isomerase are elevated in the synovial fluid of rheumatoid arthritis patients. Cha, H.S., Kim, T.J., Kim, J.Y., Lee, M.H., Jeon, C.H., Kim, J., Bae, E.K., Ahn, K.S., Koh, E.M. Scand. J. Rheumatol. (2004) [Pubmed]
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