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Query: UNIPROT:P36969 (phospholipid hydroperoxide glutathione peroxidase)
 344 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The complete amino acid sequence of the selenoprotein phospholipid-hydroperoxide glutathione peroxidase (PHGPX) from pig heart has been deduced from the corresponding genomic DNA, the cDNA covering the coding region, and by sequencing the N terminus of the protein. The maximum length of the peptide chain derived from the cDNA amounts to 170 amino acid residues. By protein sequencing the N-terminal residues methionine and cysteine of the deduced sequence were found to be cleaved. The molecular mass of 19,671 Da obtained by laser desorption mass spectroscopy, however, significantly exceeds the mean molecular mass of 19,257.09 calculated for the sequence 3-170 of PHGPX, thus indicating posttranscriptional modification. In contrast to glutathione peroxidase (GPX) the coding area of the PHGPX gene is composed of seven exons. Only the amino acid sequences encoded by the third and fifth exon are highly homologous to GPX sequences. The amino acid residues selenocysteine, tryptophan, and glutamine forming the catalytic site in bovine GPX are conserved in homologous positions of PHGPX, whereas the arginine residues presumed to bind GSH in GPX are not. Gaps in the PHGPX sequence correspond to subunit interaction sites of the tetrameric GPX. The data suggest an identical catalytic mechanism of the selenoperoxidases, a less stringent substrate specificity of PHGPX, and explain the monomeric nature of PHGPX. As in other selenoproteins, the selenocysteine residue of PHGPX is encoded by UGA. The 3'-untranslated region (UTR) of the PHGPX shows a limited consensus with that of GPX and 5'-deiodinase, where it was shown to be responsible for the decoding of UGA as selenocysteine. The 3'-UTR of PHGPX can form a stem/loop as in other mammalian selenoprotein genes. The 5'-UTR and the first intron of the PHGPX gene contain a variety of putative regulatory elements indicating hormonal control.
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PMID:Phospholipid-hydroperoxide glutathione peroxidase. Genomic DNA, cDNA, and deduced amino acid sequence. 812 51

The selenoprotein phospholipid hydroperoxide glutathione peroxidase (PHGPx) is present in at least three different isoforms in testis: as a cytosolic, as a mitochondrial, and as a nuclear protein. We have recently shown that a sperm nucleus-specific glutathione peroxidase (snGPx) is identical to the mitochondrial and cytosolic forms of PHGPx apart from its N-terminus. This arginine-rich N-terminus of snGPx, reminiscent of protamines, is encoded by an alternative exon located in the first intron of the PHGPx gene and is responsible for nuclear localisation and chromatin binding of snGPx [Pfeifer et al., FASEB J. 15 (2001), pp. 1236-1238]. By using a combination of techniques including selective cloning of mRNA 5'-ends, RT-PCR, and S1 analyses, we provide evidence that the transcript encoding the nuclear form is generated by transcription initiation at an alternative promoter and not by alternative splicing. We show that the major transcription start region is located at -12 to -14 upstream of the AUG translation initiation site of the sperm nucleus-specific exon and lacks a TATA box. Two minor TATA-less transcription initiation sites are located at around -30 and -45. We have shown by in situ hybridisation that snGPx expression in testis, like protamine expression, is restricted to late stages of spermatogenesis whereas PHGPx expression is only found in spermatocytes and early spermatids. These findings have to be taken into account when studying either the differential regulation of PHGPx and snGPx expression in testis or the impact of putative mutations in snGPx on male fertility in man.
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PMID:Testis-specific expression of the nuclear form of phospholipid hydroperoxide glutathione peroxidase (PHGPx). 1275 92

PHGPx (phospholipid hydroperoxide glutathione peroxidase) is a selenoprotein present in at least three isoforms in testis: cytosolic, mitochondrial and nuclear. All of these derive from the same gene and are structurally related with the exception of the snPHGPx (sperm nucleus-specific form), which differs from the others due to the presence of an arginine-rich N-terminus. It has been demonstrated recently that this N-terminus is encoded by an alternative exon located in the first intron of the PHGPx gene. The expression of snPHGPx has been attributed either to an alternative pre-mRNA splicing or to the presence of a distinct promoter region. Nevertheless, the exact molecular mechanism by which the expression of snPHGPx occurs has not been demonstrated so far. Preliminary sequence analysis of the region located upstream of the alternative exon revealed some potential DNA-binding sites, one of which is specific to the binding of CREM (cAMP-response element modulator) transcription factors. By using electrophoretic mobility-shift assays, we demonstrated that both nuclear protein extract from highly purified rat spermatid cells and recombinant CREM-tau protein can specifically bind to this element. Furthermore, we cloned a 1059 bp comprising the intron and the alternative exon for snPHGPx in the pCAT3 reporter vector. By transient transfection experiments, we demonstrated that the expression of the transcription factor CREM-tau can induce the activation of the reporter gene in NIH-3T3 cell line. These results were confirmed by chromatin immunoprecipitation experiments performed on highly purified rat spermatid cells. On the basis of these results, we demonstrate that snPHGPx expression is mediated by the transcription factor CREM-tau, which acts as a cis-acting element localized in the first intron of the PHGPx gene.
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PMID:cAMP-response element modulator-tau activates a distinct promoter element for the expression of the phospholipid hydroperoxide/sperm nucleus glutathione peroxidase gene. 1522 22