GSTM3 explained

Glutathione S-transferase M3 (brain), also known as GSTM2, is an enzyme which in humans is encoded by the GSTM99 gene.^{[1] [2]}

Function

Cytosolic and membrane-bound forms of glutathione S-transferase are encoded by two distinct supergene families. At present, eight distinct classes of the soluble cytoplasmic mammalian glutathione S-transferases have been identified: alpha, kappa, mu, omega, pi, sigma, theta, and zeta. This gene encodes a glutathione S-transferase that belongs to the mu class. The mu class of enzymes functions in the detoxification of electrophilic compounds, including some carcinogens, therapeutic drugs, environmental toxins and products of oxidative stress, by conjugation with glutathione. The genes encoding the mu class of enzymes are organized in a gene cluster on chromosome 1p13.3 and are known to be highly polymorphic. These genetic variations can change an individual's susceptibility to carcinogens and toxins as well as affect the toxicity and efficacy of certain drugs. Mutations of this class mu gene have been linked with a slight increase in a number of cancers, likely due to exposure with environmental toxins.

Further reading

• Bogaards JJ, van Ommen B, van Bladeren PJ . Purification and characterization of eight glutathione S-transferase isoenzymes of hamster. Comparison of subunit composition of enzymes from liver, kidney, testis, pancreas and trachea. . 286 . Biochem. J. . (Pt 2) . 383–8 . 1992 . 2 . 1530570 . 10.1042/bj2860383. 1132909 .
• Campbell E, Takahashi Y, Abramovitz M, etal . A distinct human testis and brain mu-class glutathione S-transferase. Molecular cloning and characterization of a form present even in individuals lacking hepatic type mu isoenzymes. . J. Biol. Chem. . 265 . 16 . 9188–93 . 1990 . 10.1016/S0021-9258(19)38830-1 . 2345169 . free .
• Hussey AJ, Hayes JD . Human Mu-class glutathione S-transferases present in liver, skeletal muscle and testicular tissue. . Biochim. Biophys. Acta . 1203 . 1 . 131–41 . 1993 . 8218382 . 10.1016/0167-4838(93)90047-U .
• Anttila S, Hirvonen A, Vainio H, etal . Immunohistochemical localization of glutathione S-transferases in human lung. . Cancer Res. . 53 . 23 . 5643–8 . 1994 . 8242618 .
• Pearson WR, Vorachek WR, Xu SJ, etal . Identification of class-mu glutathione transferase genes GSTM1-GSTM5 on human chromosome 1p13. . Am. J. Hum. Genet. . 53 . 1 . 220–33 . 1993 . 8317488 . 1682241 .
• Ross VL, Board PG . Molecular cloning and heterologous expression of an alternatively spliced human Mu class glutathione S-transferase transcript. . 294 . Biochem. J. . (Pt 2) . 373–80 . 1993 . 2 . 8373352 . 10.1042/bj2940373. 1134464 .
• Gough AC, Zhong S, Wolf CR, Spurr NK . Chromosome assignment of the human glutathione S-transferase mu 3 gene (GSTM3) to chromosome 1 by gene specific polymerase chain reaction . Cytogenet. Cell Genet. . 65 . 1–2 . 111–4 . 1993 . 8404061 . 10.1159/000133613 .
• Takahashi Y, Campbell EA, Hirata Y, etal . A basis for differentiating among the multiple human Mu-glutathione S-transferases and molecular cloning of brain GSTM5. . J. Biol. Chem. . 268 . 12 . 8893–8 . 1993 . 10.1016/S0021-9258(18)52957-4 . 8473333 . free .
• Hand PA, Inskip A, Gilford J, etal . Allelism at the glutathione S-transferase GSTM3 locus: interactions with GSTM1 and GSTT1 as risk factors for astrocytoma. . Carcinogenesis . 17 . 9 . 1919–22 . 1996 . 8824514 . 10.1093/carcin/17.9.1919 . free .
• Rowe JD, Nieves E, Listowsky I . Subunit diversity and tissue distribution of human glutathione S-transferases: interpretations based on electrospray ionization-MS and peptide sequence-specific antisera. . 325 . Biochem. J. . (Pt 2) . 481–6 . 1997 . 2 . 10.1042/bj3250481 . 9230131 . 1218585 .
• Macé K, Bowman ED, Vautravers P, etal . Characterisation of xenobiotic-metabolising enzyme expression in human bronchial mucosa and peripheral lung tissues. . Eur. J. Cancer . 34 . 6 . 914–20 . 1998 . 9797707 . 10.1016/S0959-8049(98)00034-3 .
• Patskovsky YV, Huang MQ, Takayama T, etal . Distinctive structure of the human GSTM3 gene-inverted orientation relative to the mu class glutathione transferase gene cluster. . Arch. Biochem. Biophys. . 361 . 1 . 85–93 . 1999 . 9882431 . 10.1006/abbi.1998.0964 .
• Yang GP, Ross DT, Kuang WW, etal . Combining SSH and cDNA microarrays for rapid identification of differentially expressed genes. . Nucleic Acids Res. . 27 . 6 . 1517–23 . 1999 . 10037815 . 10.1093/nar/27.6.1517 . 148347 .
• Patskovsky YV, Patskovska LN, Listowsky I . An asparagine-phenylalanine substitution accounts for catalytic differences between hGSTM3-3 and other human class mu glutathione S-transferases. . Biochemistry . 38 . 49 . 16187–94 . 2000 . 10587441 . 10.1021/bi991714t .
• Buch SC, Notani PN, Bhisey RA . Polymorphism at GSTM1, GSTM3 and GSTT1 gene loci and susceptibility to oral cancer in an Indian population. . Carcinogenesis . 23 . 5 . 803–7 . 2002 . 12016153 . 10.1093/carcin/23.5.803 . free .
• Strausberg RL, Feingold EA, Grouse LH, etal . Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. . Proc. Natl. Acad. Sci. U.S.A. . 99 . 26 . 16899–903 . 2003 . 12477932 . 10.1073/pnas.242603899 . 139241 . 2002PNAS...9916899M . free .
• Medeiros R, Vasconcelos A, Costa S, etal . Metabolic susceptibility genes and prostate cancer risk in a southern European population: the role of glutathione S-transferases GSTM1, GSTM3, and GSTT1 genetic polymorphisms. . Prostate . 58 . 4 . 414–20 . 2004 . 14968442 . 10.1002/pros.10348 . 11087022 .
• Gerhard DS, Wagner L, Feingold EA, etal . The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). . Genome Res. . 14 . 10B . 2121–7 . 2004 . 15489334 . 10.1101/gr.2596504 . 528928 .
• Tchaikovskaya T, Fraifeld V, Urphanishvili T, etal . Glutathione S-transferase hGSTM3 and ageing-associated neurodegeneration: relationship to Alzheimer's disease. . Mech. Ageing Dev. . 126 . 2 . 309–15 . 2005 . 15621212 . 10.1016/j.mad.2004.08.029 . 34399866 .
• Liu X, Campbell MR, Pittman GS, etal . Expression-based discovery of variation in the human glutathione S-transferase M3 promoter and functional analysis in a glioma cell line using allele-specific chromatin immunoprecipitation. . Cancer Res. . 65 . 1 . 99–104 . 2005 . 10.1158/0008-5472.99.65.1 . 15665284 . 7707090 . free .

Notes and References

1. Web site: Entrez Gene: GSTM3 glutathione S-transferase M3 (brain).
2. Campbell E, Takahashi Y, Abramovitz M, Peretz M, Listowsky I . A distinct human testis and brain mu-class glutathione S-transferase. Molecular cloning and characterization of a form present even in individuals lacking hepatic type mu isoenzymes . J. Biol. Chem. . 265 . 16 . 9188–93 . June 1990 . 10.1016/S0021-9258(19)38830-1 . 2345169 . free .