Cloning, sequencing and characterization of the human Alpha glutathione S-transferase gene corresponding to the cDNA clone pGTH2

Abstract

The human Alpha glutathione S-transferase gene corresponding to the human liver cDNA clone pGTH2 was isolated from a cosmid genome library. The gene, represented by the clone cosGTH2, spans nearly 12 kb and contains seven exons. The intron/exon borders conform to the standard rules, and an open reading frame is present, starting at position 67 in exon 2, the double-stop codon being at position 733 in exon 7. Exons 1, 2 and 7 differ in length from the known rat gene coding for the Ya enzyme. A 209 bp 5'-upstream region contains TATA and CAT boxes and, in addition, motifs for Spl-, NFl-and HNFI-binding factors. Clone cosGTH2 represents the less basic subunit, ay, of two Alpha glutathione S-transferase subunits (ax and ac) expressed in liver, which is identical with the kidney subunit a2

Characterization of the rat glutathione S-transferase Yc2 subunit gene, GSTA5: identification of a putative antioxidant-responsive element in the 5′-flanking region of rat GSTA5 that may mediate chemoprotection against aflatoxin B1

“…GSTA3 and GSTA5). The rat GSTA5 gene is approximately 12 kb in size and is thus of similar size to other class Alpha GSTs described to date [24,[27][28][29][30][31][32]. However, unlike other class Alpha GST genes described previously, all of which comprise seven exons, rat GSTA5 is composed of only six exons.…”

“…In the GSTA5 gene the transcription start site and translation initiation codon are both contained within the first exon, while in other class Alpha GST genes the transcription start site and translation initiation codon are represented in exon one and exon two, respectively. By comparison with other class Alpha GST genes which have been characterized hitherto, rat GSTA5 would appear to lack the intron equivalent to that found in the 5h-flanking noncoding region of other class Alpha GST genes ; in rat GSTA2 and mouse GstA1 intron 1 is found 22 bp upstream from the ATG initiation codon [27,28] while in human GSTA1 and GSTA2 intron 1 is found 30 bp upstream from the initiation codon [29][30][31][32]. It is possible that the presence or absence of an intron in the 5h non-coding region of class Alpha GST genes represents a characteristic difference between those encoding Ya-type (GSTA1 and A2) and Yc-type (GSTA3 and A5) subunits.…”

Review

“…These studies indicated the presence of multiple genes for the alpha class. This has been confirmed by Southern blot analysis of human genomic DMA using either a cDNA probe or a putative promoter probe comprising the 746 bp 5'-upstream sequence of cos GTH2 (Klöne et al, 1992), which represents a GSTA2 gene. So far only three distinct GST alpha genes have been reported.…”

“…References Rozen et al, 1992Klöne et al, 1992 Röhrdanz ef a/., 1992 Suzuki et al, 1993Tu and Qian, 1986Klöne et al, 1992Rhoads et al, 1987Ahmad et al, 1993Singhalefa/,,1994 a The coding sequence of this GSTA2 gene differs by two bases from the corresponding cDNA and from the gene isolated by Klöne ef a/. (1992).…”

“…So far only three distinct GST alpha genes have been reported. The GSTA1 and GSTA2 genes have been isolated and characterized (Klöne et al, 1992;Röhrdanz ei al., 1992;Rozen et al, 1992) and are each 12-13 kb in length. While GSTA1 and GSTA2 genes are divided into seven exons and have an intron/exon structure identical to that of the rat alpha genes, in the GSTA3 gene, recently characterized by Suzuki etal.…”