Abstract
We have isolated the human gene and cDNA that encode the fourth member of the Mu class glutathione S-transferases (GSTs). The complete gene sequence (GenBank M96233) and the cDNA sequence (M96234) are reported and named GSTM4. The gene, located on chromosome 1, is comprised of eight exons with an organization similar to that of other Mu class genes. GSTM4 differs from a partial gene sequence, termed GSTmu2 (Taylor, J. B., Oliver, J., Sherrington, R., and Pemble, S. E. (1991) Biochem. J. 274, 587-593), in exons 3 through 5 by only 11 nucleotides within introns. The cDNA for GSTM4 was isolated from a library derived from the cervical carcinoma cell line, HeLa. Northern blots demonstrate the presence of GSTM4 mRNA in human heart, placenta, lung, brain, liver, skeletal muscle, pancreas, testis, cerebral cortex, uterus, ovary, a lymphoblastoid cell line, and four carcinoma cell lines. The deduced amino acid sequence of GSTM4 is 87% (GSTM1), 83% (GSTM2), and 70% (GSTM3) identical to the previously described human Mu class GSTs. The polypeptide encoded by the GSTM4 cDNA, produced in a bacterial expression system, conjugates 1-chloro-2,4-dinitrobenzene to GSH with a specific activity of 1.39 +/- 0.21 mumol/min/mg.
Highlights
GSTM4 is 87% (GSTMl), 83% (GSTM2), and 70% product of one of these alleles, GSTMla-la, was first isolated (GSTM3)identical to the previously described human fromliver (Warholm et al, 1980) andhas ahigh level of
A substantial portionof human livers and lymphocytes display thisphenotype of deficiency of GSTMl Many detoxification enzymes exist as isozymes with over- activity(SeidegardandPero, 1985; Warholm et al, 1980)
The presenceof multiple, closely related gene et al, 1988; Seidegard et al, 1988), it wasshown that the products provides a broad substrate specificity and thereby GSTMl null phenotype was due toa homozygous deletion of allows detoxification of a wide variety of xenobiotics
Summary
1) To whom correspondence shouldbe addressed Div. of Hematolal., 1992). Additional human Muclass GSTs forwhich cDNA sequences are published include GSTM2-2, whose deduced amino acidsequence matchesthe 24 NHp-terminalamino acids of a Mu class GST expressed in muscle (Board et al, 1988; Vorachek et al, 1991) and GSTM3-3,identified in ogy and Medical Oncology, Oregon Health Sciences University, Mail human testis and brain(Campbell et al, 1990). Code L586,3181 S.W. Sam Jackson ParkRd., Portland, OR 97201
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