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Gene Review

GSTA4  -  glutathione S-transferase alpha 4

Homo sapiens

Synonyms: GST class-alpha member 4, GSTA4-4, GTA4, Glutathione S-transferase A4, Glutathione S-transferase A4-4
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Disease relevance of GSTA4

  • The encoded GSTA4-4 enzyme was expressed in Escherichia coli and was found to be immunologically distinct from GSTA1-1 and to have high activity with alk-2-enals [1].
  • Molecular implications of the human glutathione transferase A-4 gene (hGSTA4) polymorphisms in neurodegenerative diseases [2].
  • These findings are consistent with capillary growth by subdivision being the main mechanism of glomerular hypertrophy when nephron loss occurs during childhood, and the identity of the regressions of N versus GTA4 in RN and controls suggests that compensatory hypertrophy resembles the normal glomerular growth pattern in this age group [3].

High impact information on GSTA4

  • Butyrate induced GSTP1, GSTM2, and GSTA4 in HT29 as previously confirmed by other methods (northern blot/qPCR) [4].
  • By searching the human genome sequence database with human hGSTA1 and hGSTA4 cDNA sequences, we identified three PAC and one BAC clones covering more than 400 kilobases and containing the entire GST alpha gene cluster [5].
  • Identification of cDNAs encoding two human alpha class glutathione transferases (GSTA3 and GSTA4) and the heterologous expression of GSTA4-4 [1].
  • A second cDNA, termed GSTA4, was identified in a brain cDNA library [1].
  • The homodimeric protein hGSTA4-4, is involved in the detoxification of 4-hydroxynonenal and other reactive electrophiles produced by oxidative metabolism, and may have a significant role in protecting intracellular components from oxidative damage [6].

Biological context of GSTA4


Anatomical context of GSTA4


Associations of GSTA4 with chemical compounds


Other interactions of GSTA4


Analytical, diagnostic and therapeutic context of GSTA4


  1. Identification of cDNAs encoding two human alpha class glutathione transferases (GSTA3 and GSTA4) and the heterologous expression of GSTA4-4. Board, P.G. Biochem. J. (1998) [Pubmed]
  2. Molecular implications of the human glutathione transferase A-4 gene (hGSTA4) polymorphisms in neurodegenerative diseases. Coppedè, F., Armani, C., Bidia, D.D., Petrozzi, L., Bonuccelli, U., Migliore, L. Mutat. Res. (2005) [Pubmed]
  3. Glomerular morphometry in childhood reflux nephropathy, emphasizing the capillary changes. Akaoka, K., White, R.H., Raafat, F. Kidney Int. (1995) [Pubmed]
  4. Butyrate may enhance toxicological defence in primary, adenoma and tumor human colon cells by favourably modulating expression of glutathione S-transferases genes, an approach in nutrigenomics. Pool-Zobel, B.L., Selvaraju, V., Sauer, J., Kautenburger, T., Kiefer, J., Richter, K.K., Soom, M., Wölfl, S. Carcinogenesis (2005) [Pubmed]
  5. The human glutathione transferase alpha locus: genomic organization of the gene cluster and functional characterization of the genetic polymorphism in the hGSTA1 promoter. Morel, F., Rauch, C., Coles, B., Le Ferrec, E., Guillouzo, A. Pharmacogenetics (2002) [Pubmed]
  6. Genomic organization, 5'-flanking region and chromosomal localization of the human glutathione transferase A4 gene. Desmots, F., Rauch, C., Henry, C., Guillouzo, A., Morel, F. Biochem. J. (1998) [Pubmed]
  7. Comparative expression of two alpha class glutathione S-transferases in human adult and prenatal liver tissues. Gallagher, E.P., Gardner, J.L. Biochem. Pharmacol. (2002) [Pubmed]
  8. Genotoxicity of 4-hydroxy-2-nonenal in human colon tumor cells is associated with cellular levels of glutathione and the modulation of glutathione S-transferase A4 expression by butyrate. Knoll, N., Ruhe, C., Veeriah, S., Sauer, J., Glei, M., Gallagher, E.P., Pool-Zobel, B.L. Toxicol. Sci. (2005) [Pubmed]
  9. Several glutathione S-transferase isozymes that protect against oxidative injury are expressed in human liver mitochondria. Gallagher, E.P., Gardner, J.L., Barber, D.S. Biochem. Pharmacol. (2006) [Pubmed]
  10. Glutathione-S-transferase A4-4 modulates oxidative stress in endothelium: possible role in human atherosclerosis. Yang, Y., Yang, Y., Trent, M.B., He, N., Lick, S.D., Zimniak, P., Awasthi, Y.C., Boor, P.J. Atherosclerosis (2004) [Pubmed]
  11. Development of a peptide antibody specific to human glutathione S-transferase alpha 4-4 (hGSTA4-4) reveals preferential localization in human liver mitochondria. Gardner, J.L., Gallagher, E.P. Arch. Biochem. Biophys. (2001) [Pubmed]
  12. Gene expression profiles characterize early graft response in living donor small bowel transplantation: a case report. Bradley, S.P., Pahari, M., Uknis, M.E., Rastellini, C., Cicalese, L. Transplant. Proc. (2006) [Pubmed]
  13. Effects of phenytoin on glutathione status and oxidative stress biomarker gene mRNA levels in cultured precision human liver slices. Gallagher, E.P., Sheehy, K.M. Toxicol. Sci. (2001) [Pubmed]
  14. Depletion of 4-hydroxynonenal in hGSTA4-transfected HLE B-3 cells results in profound changes in gene expression. Patrick, B., Li, J., Jeyabal, P.V., Reddy, P.M., Yang, Y., Sharma, R., Sinha, M., Luxon, B., Zimniak, P., Awasthi, S., Awasthi, Y.C. Biochem. Biophys. Res. Commun. (2005) [Pubmed]
  15. 4-Hydroxynonenal induces mitochondrial oxidative stress, apoptosis and expression of glutathione S-transferase A4-4 and cytochrome P450 2E1 in PC12 cells. Raza, H., John, A. Toxicol. Appl. Pharmacol. (2006) [Pubmed]
  16. Two distinct 4-hydroxynonenal metabolizing glutathione S-transferase isozymes are differentially expressed in human tissues. Cheng, J.Z., Yang, Y., Singh, S.P., Singhal, S.S., Awasthi, S., Pan, S.S., Singh, S.V., Zimniak, P., Awasthi, Y.C. Biochem. Biophys. Res. Commun. (2001) [Pubmed]
  17. Lipid peroxidation and cell cycle signaling: 4-hydroxynonenal, a key molecule in stress mediated signaling. Yang, Y., Sharma, R., Sharma, A., Awasthi, S., Awasthi, Y.C. Acta Biochim. Pol. (2003) [Pubmed]
  18. Transfection with 4-hydroxynonenal-metabolizing glutathione S-transferase isozymes leads to phenotypic transformation and immortalization of adherent cells. Sharma, R., Brown, D., Awasthi, S., Yang, Y., Sharma, A., Patrick, B., Saini, M.K., Singh, S.P., Zimniak, P., Singh, S.V., Awasthi, Y.C. Eur. J. Biochem. (2004) [Pubmed]
  19. Role of the media in vascular injury: atherosclerosis and dissection. Boor, P.J., Yang, Y., Gong, B. Toxicologic pathology. (2006) [Pubmed]
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