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Gene Review

GSTA2  -  glutathione S-transferase alpha 2

Homo sapiens

Synonyms: GST HA subunit 2, GST class-alpha member 2, GST-gamma, GST2, GSTA2-2, ...
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Disease relevance of GSTA2


High impact information on GSTA2


Biological context of GSTA2

  • We detected an upregulation of GSTs (GSTA2, GSTT2) that are known to be involved in the defence against oxidative stress in primary cells upon incubation with butyrate [8].
  • Nevertheless, the rare genotypes, GSTA2*E/*E and GSTA1*B/*B + GSTA2*C/*C (potential low GSTA2 activity and low hepatic GSTA1 and GSTA2 expression, respectively) could increase the risk of adverse effects of xenobiotics via compromised efficiency of detoxification [2].
  • Polymerase chain reaction/restriction fragment length polymorphism analysis revealed the existence of three variants, a silent base substitution, K125K (G365A) in GSTA1, and T112S and E210A in GSTA2, in European Australian, African and Chinese populations [1].
  • A genetic polymorphism in the 5'-regulatory sequence of hGSTA1 has been shown to correlate with the relative and absolute levels of expression of GSTA1/GSTA2 in human liver [9].
  • Constructs consisting of the proximal promoters of hGSTA1*A, hGSTA1*B or hGSTA2, with luciferase as a reporter gene, showed differential expression when transfected into HepG2 cells: hGSTA1*A approximately hGSTA2 > hGSTA1*B [10].

Anatomical context of GSTA2

  • GSTA1 and GSTA2 were expressed at high levels in duodenum and small intestine and expression decreased from proximal to distal small intestine [11].
  • Two distinct cDNAs corresponding to GSTA1 and GSTA2 genes encoding glutathione S-transferases (GSTs) from the hepatopancreas of red sea bream, Pagrus major were cloned and sequenced [12].
  • HLE B-3 cell membranes were prepared, peroxidized, and used to examine whether hGSTA1-1 and hGSTA2-2 catalyzes the reduction of membrane PL-OOH in situ using the microiodometric and spectrophotometric assays [13].
  • Compared to parental MCF-7 or pSV2neotransfected control cell lines, covalent labeling of total cellular macromolecules by [3H]NQO (0.1-1.0 mM) was reduced by 70% and 92% in hGSTP1-1- and mGSTM1-1-transfected cell lines, respectively, but was not affected in the hGSTA2-2 expressing line [14].
  • The GST2 isozymes are not detectable in erythrocytes, platelets, cultured fibroblasts or lymphocytoid cells but are found in many other tissues, including fetal liver [15].

Associations of GSTA2 with chemical compounds


Physical interactions of GSTA2

  • These results suggest that PXR interacts with factors binding to the ARE to elicit the pregnane inductive response for GSTA2 [19].

Regulatory relationships of GSTA2


Other interactions of GSTA2


Analytical, diagnostic and therapeutic context of GSTA2


  1. Polymorphism of human Alpha class glutathione transferases. Tetlow, N., Liu, D., Board, P. Pharmacogenetics (2001) [Pubmed]
  2. Human glutathione S-transferase A2 polymorphisms: variant expression, distribution in prostate cancer cases/controls and a novel form. Ning, B., Wang, C., Morel, F., Nowell, S., Ratnasinghe, D.L., Carter, W., Kadlubar, F.F., Coles, B. Pharmacogenetics (2004) [Pubmed]
  3. Human glutathione S-transferases. The Ha multigene family encodes products of different but overlapping substrate specificities. Chow, N.W., Whang-Peng, J., Kao-Shan, C.S., Tam, M.F., Lai, H.C., Tu, C.P. J. Biol. Chem. (1988) [Pubmed]
  4. Isolation of a cDNA clone and localization of human glutathione S-transferase 2 genes to chromosome band 6p12. Board, P.G., Webb, G.C. Proc. Natl. Acad. Sci. U.S.A. (1987) [Pubmed]
  5. Increased protein stability as a mechanism that enhances Nrf2-mediated transcriptional activation of the antioxidant response element. Degradation of Nrf2 by the 26 S proteasome. Nguyen, T., Sherratt, P.J., Huang, H.C., Yang, C.S., Pickett, C.B. J. Biol. Chem. (2003) [Pubmed]
  6. Role of glutathione S-transferases in protection against lipid peroxidation. Overexpression of hGSTA2-2 in K562 cells protects against hydrogen peroxide-induced apoptosis and inhibits JNK and caspase 3 activation. Yang, Y., Cheng, J.Z., Singhal, S.S., Saini, M., Pandya, U., Awasthi, S., Awasthi, Y.C. J. Biol. Chem. (2001) [Pubmed]
  7. Role of p90 ribosomal S6-kinase-1 in oltipraz-induced specific phosphorylation of CCAAT/enhancer binding protein-beta for GSTA2 gene transactivation. Lee, S.J., Kim, S.G. Mol. Pharmacol. (2006) [Pubmed]
  8. 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]
  9. The role of human glutathione S-transferases (hGSTs) in the detoxification of the food-derived carcinogen metabolite N-acetoxy-PhIP, and the effect of a polymorphism in hGSTA1 on colorectal cancer risk. Coles, B., Nowell, S.A., MacLeod, S.L., Sweeney, C., Lang, N.P., Kadlubar, F.F. Mutat. Res. (2001) [Pubmed]
  10. Effect of polymorphism in the human glutathione S-transferase A1 promoter on hepatic GSTA1 and GSTA2 expression. Coles, B.F., Morel, F., Rauch, C., Huber, W.W., Yang, M., Teitel, C.H., Green, B., Lang, N.P., Kadlubar, F.F. Pharmacogenetics (2001) [Pubmed]
  11. Interindividual variation and organ-specific patterns of glutathione S-transferase alpha, mu, and pi expression in gastrointestinal tract mucosa of normal individuals. Coles, B.F., Chen, G., Kadlubar, F.F., Radominska-Pandya, A. Arch. Biochem. Biophys. (2002) [Pubmed]
  12. Molecular cloning and characterization of alpha-class glutathione S-transferase genes from the hepatopancreas of red sea bream, Pagrus major. Konishi, T., Kato, K., Araki, T., Shiraki, K., Takagi, M., Tamaru, Y. Comp. Biochem. Physiol. C Toxicol. Pharmacol. (2005) [Pubmed]
  13. Protection of HLE B-3 cells against hydrogen peroxide- and naphthalene-induced lipid peroxidation and apoptosis by transfection with hGSTA1 and hGSTA2. Yang, Y., Sharma, R., Cheng, J.Z., Saini, M.K., Ansari, N.H., Andley, U.P., Awasthi, S., Awasthi, Y.C. Invest. Ophthalmol. Vis. Sci. (2002) [Pubmed]
  14. Protection by transfected glutathione S-transferase isozymes against carcinogen-induced alkylation of cellular macromolecules in human MCF-7 cells. Fields, W.R., Li, Y., Townsend, A.J. Carcinogenesis (1994) [Pubmed]
  15. The human glutathione S-transferases: studies on the tissue distribution and genetic variation of the GST1, GST2 and GST3 isozymes. Strange, R.C., Faulder, C.G., Davis, B.A., Hume, R., Brown, J.A., Cotton, W., Hopkinson, D.A. Ann. Hum. Genet. (1984) [Pubmed]
  16. Structure and expression of a cluster of glutathione S-transferase genes from a marine fish, the plaice (Pleuronectes platessa). Leaver, M.J., Wright, J., George, S.G. Biochem. J. (1997) [Pubmed]
  17. Overexpression of GSTA2 protects against cell cycle arrest and apoptosis induced by the DNA inter-strand crosslinking nitrogen mustard, mechlorethamine. Xie, J., Shults, K., Flye, L., Jiang, F., Head, D.R., Briggs, R.C. J. Cell. Biochem. (2005) [Pubmed]
  18. Structure and function of the 5' flanking sequences of the human alpha class glutathione S-transferase genes. Suzuki, T., Smith, S., Board, P.G. Biochem. Biophys. Res. Commun. (1994) [Pubmed]
  19. Regulation of the rat glutathione S-transferase A2 gene by glucocorticoids: involvement of both the glucocorticoid and pregnane X receptors. Falkner, K.C., Pinaire, J.A., Xiao, G.H., Geoghegan, T.E., Prough, R.A. Mol. Pharmacol. (2001) [Pubmed]
  20. Stereoselectivity of human liver and intestinal cytosolic fractions as well as purified human glutathione S-transferase isoenzymes towards 2-bromoisovalerylurea enantiomers. Mulders, T.M., van Ommen, B., van Bladeren, P.J., Breimer, D.D., Mulder, G.J. Biochem. Pharmacol. (1993) [Pubmed]
  21. Functional polymorphism of human glutathione transferase A2. Tetlow, N., Board, P.G. Pharmacogenetics (2004) [Pubmed]
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