The protein encoded by this gene belongs to the glutathione peroxidase family, members of which catalyze the reduction of hydrogen peroxide, organic hydroperoxides and lipid hydroperoxides, and thereby protect cells against oxidative damage. Several isozymes of this gene family exist in vertebrates, which vary in cellular location and substrate specificity. This isozyme has a high preference for lipid hydroperoxides and protects cells against membrane lipid peroxidation and cell death. It is also required for normal sperm development; thus, it has been identified as a 'moonlighting' protein because of its ability to serve dual functions as a peroxidase, as well as a structural protein in mature spermatozoa. Disruption of this gene in mouse spermatocytes is associated with male infertility. This isozyme is also a selenoprotein, containing the rare amino acid selenocysteine (Sec) at its active site. Sec is encoded by the UGA codon, which normally signals translation termination. The 3' UTRs of selenoprotein mRNAs contain a conserved stem-loop structure, designated the Sec insertion sequence (SECIS) element, that is necessary for the recognition of UGA as a Sec codon, rather than as a stop signal. Alternatively spliced transcript variants have been found for this gene. Pseudogenes of this locus have been identified on chromosomes 10 and 17. [provided by RefSeq, Aug 2017].
Selenium Utilization by GPX4 Is Required to Prevent Hydroperoxide-Induced Ferroptosis.
Ingold I, Berndt C, Schmitt S, Doll S, Poschmann G, Buday K, Roveri A, Peng X, Porto Freitas F, Seibt T, Mehr L, Aichler M, Walch A, Lamp D, Jastroch M, Miyamoto S, Wurst W, Ursini F, Arn?r ESJ, Fradejas-Villar N, Schweizer U, Zischka H, Friedmann Angeli JP, Conrad M Cell(2017 Dec)
The following Gpx4 gene cDNA ORF clone sequences were retrieved from the NCBI Reference Sequence Database (RefSeq). These sequences represent the protein coding region of the Gpx4 cDNA ORF which is encoded by the open reading frame (ORF) sequence. ORF sequences can be delivered in our standard vector, pcDNA3.1+/C-(K)DYK or the vector of your choice as an expression/transfection-ready ORF clone. Not the clone you want? Click here to find your clone.
phospholipid hydroperoxide glutathione peroxidase isoform A precursor
Comment
Comment: REVIEWED REFSEQ: This record has been curated by NCBI staff. The reference sequence was derived from BY238083.1, AK006441.1 and CX733872.1. On Jan 6, 2019 this sequence version replaced NM_008162.3.
Transcript Variant: This variant (1) represents the predominant transcript and encodes the canonical isoform A (also known as phGPx). A similar isoform in rat(L-form) has been shown to be localized to the mitochondria (PMID:9988735).
Publication Note: This RefSeq record includes a subset of the publications that are available for this gene. Please see the Gene record to access additional publications.
##Evidence-Data-START##
Transcript exon combination :: AK168027.1, D87896.1 [ECO:0000332]
RNAseq introns :: single sample supports all introns SAMN00849374, SAMN00849375 [ECO:0000348]
##Evidence-Data-END##
##RefSeq-Attributes-START##
gene product(s) localized to mito. :: PMID: 19417079; reported by MitoCarta
multifunctional gene product(s) :: inferred from conservation
protein contains selenocysteine :: PMID: 9370288
##RefSeq-Attributes-END##
COMPLETENESS: full length.
phospholipid hydroperoxide glutathione peroxidase, mitochondrial isoform A precursor
Comment
Comment: REVIEWED REFSEQ: This record has been curated by NCBI staff. The reference sequence was derived from AC159999.6, BY238083.1, AK006441.1 and AA510431.1. On Jan 22, 2014 this sequence version replaced NM_008162.2.
Transcript Variant: This variant (1) represents the predominant transcript and encodes the canonical isoform A (also known as phGPx). A similar isoform in rat has been shown to be localized to the mitochondria (PMID:9988735).
Publication Note: This RefSeq record includes a subset of the publications that are available for this gene. Please see the Gene record to access additional publications.
##Evidence-Data-START##
Transcript exon combination :: D87896.1, AF045768.1 [ECO:0000332]
RNAseq introns :: single sample supports all introns SAMN00849374, SAMN00849375 [ECO:0000348]
##Evidence-Data-END##
##RefSeq-Attributes-START##
gene product(s) localized to mito. :: PMID: 19417079; reported by MitoCarta
multifunctional gene product(s) :: inferred from conservation
protein contains selenocysteine :: PMID: 9370288
##RefSeq-Attributes-END##
COMPLETENESS: complete on the 3' end.
phospholipid hydroperoxide glutathione peroxidase isoform C
Comment
Comment: REVIEWED REFSEQ: This record has been curated by NCBI staff. The reference sequence was derived from AK006441.1 and CX733872.1.
Transcript Variant: This variant (4) uses an alternate promoter, which results in translation initiation from an in-frame downstream AUG start codon compared to variant 1. The encoded isoform (C) has a shorter N-terminus compared to isoform A. A similar isoform in rat (S-form) has been reported to be localized to the cytoplasm (PMID:9988735).
Publication Note: This RefSeq record includes a subset of the publications that are available for this gene. Please see the Gene record to access additional publications.
##Evidence-Data-START##
Transcript exon combination :: AK168027.1, AF045768.1 [ECO:0000332]
RNAseq introns :: single sample supports all introns SAMN00849374, SAMN00849375 [ECO:0000348]
##Evidence-Data-END##
##RefSeq-Attributes-START##
gene product(s) localized to mito. :: PMID: 19417079; reported by MitoCarta
multifunctional gene product(s) :: inferred from conservation
protein contains selenocysteine :: PMID: 9370288
##RefSeq-Attributes-END##
COMPLETENESS: full length.
phospholipid hydroperoxide glutathione peroxidase isoform B
Comment
Comment: REVIEWED REFSEQ: This record has been curated by NCBI staff. The reference sequence was derived from AC159999.6, AK006441.1 and AA510431.1. On Jan 22, 2014 this sequence version replaced NM_001037741.2.
Transcript Variant: This variant (2) contains an alternate 5' terminal exon compared to variant 1. The resulting isoform (B, also know as snGPx) has a longer and a distinct N-terminus compared to isoform A. A similar isoform in rat has been reported to be localized in the sperm nucleus (PMID:11344099).
Sequence Note: This RefSeq record was created from transcript and genomic sequence data to make the sequence consistent with the reference genome assembly. The genomic coordinates used for the transcript record were based on transcript alignments.
Publication Note: This RefSeq record includes a subset of the publications that are available for this gene. Please see the Gene record to access additional publications.
##Evidence-Data-START##
Transcript exon combination :: AF274027.1, AB072797.1 [ECO:0000332]
RNAseq introns :: single sample supports all introns SAMN00849374, SAMN00849375 [ECO:0000348]
##Evidence-Data-END##
##RefSeq-Attributes-START##
gene product(s) localized to mito. :: PMID: 19417079; reported by MitoCarta
multifunctional gene product(s) :: inferred from conservation
protein contains selenocysteine :: PMID: 9370288
##RefSeq-Attributes-END##
COMPLETENESS: complete on the 3' end.
phospholipid hydroperoxide glutathione peroxidase isoform B
Comment
Comment: REVIEWED REFSEQ: This record has been curated by NCBI staff. The reference sequence was derived from AC159999.6, AK006441.1 and CX733872.1. On Jan 6, 2019 this sequence version replaced NM_001037741.3.
Transcript Variant: This variant (2) contains an alternate 5' terminal exon compared to variant 1. The resulting isoform (B) has a longer and a distinct N-terminus compared to isoform A. A similar isoform in rat (snGPx) has been reported to be localized in the sperm nucleus (PMID:11344099).
Sequence Note: This RefSeq record was created from transcript and genomic sequence data to make the sequence consistent with the reference genome assembly. The genomic coordinates used for the transcript record were based on transcript alignments.
Publication Note: This RefSeq record includes a subset of the publications that are available for this gene. Please see the Gene record to access additional publications.
##Evidence-Data-START##
Transcript exon combination :: AF274027.1, AB072797.1 [ECO:0000332]
RNAseq introns :: single sample supports all introns SAMN00849374, SAMN00849375 [ECO:0000348]
##Evidence-Data-END##
##RefSeq-Attributes-START##
gene product(s) localized to mito. :: PMID: 19417079; reported by MitoCarta
multifunctional gene product(s) :: inferred from conservation
protein contains selenocysteine :: PMID: 9370288
##RefSeq-Attributes-END##
COMPLETENESS: full length.
User Manual
NM_008162.4
