Sequence of a cDNA coding for human glutathione peroxidase confirms TGA encodes active site selenocysteine

Selenium dependent glutathione peroxidase (1) is a nuclear encoded cytosolic and mitochondrial enzyme which maintains the integrity of DNA and lipids as well as reducing levels of endogenous hydrogen peroxide as follows: ROOH + 2GSH — GSSG + ROH + IL,O where ROOH represents peroxidized DNA (2), lipid hydroperoxides, membrane-associated phospholipid hydroperoxides or hydrogen peroxide. We have isolated a cDNA coding the human enzyme from a kidney library in XgtlO by cross-hybridization with a bovine cDNA (3); 24 of 5300 clones hybridized with the probe. The active site selenocysteine residue (-CILSeH) at position 47 (i.e. SeC) is encoded by the nonsense codon, TGA, as is similarly observed in the mouse gene (4). Interestingly evidence suggests that the selenium atom is incorporated cotranslationally (5) rather than via a posttranslational modification step. This clone possesses 5 bp of the 5'-untranslated region, the 603 bp coding region, 223 bp of the 3'-untranslated region and a canonical polyadenylation signal, AATAAA, upstream of the polyA tract. The amino acid sequence reveals the protein possesse