Gene/Proteome Database (LMPD)
LMPD ID
LMP002781
Gene ID
Species
Mus musculus (Mouse)
Gene Name
glutathione peroxidase 4
Gene Symbol
Synonyms
GPx-4; GSHPx-4; PHGPx; mtPHGPx; snGPx
Alternate Names
phospholipid hydroperoxide glutathione peroxidase, nuclear; sperm nuclei glutathione peroxidase; phospholipid hydroperoxide glutathione peroxidase, mitochondrial
Chromosome
10
Map Location
10 C1|10 39.72 cM
EC Number
1.11.1.12
Summary
This gene encodes a member of the glutathione peroxidase protein family. Glutathione peroxidase catalyzes the reduction of hydrogen peroxide, organic hydroperoxide, and lipid peroxides by reduced glutathione and functions in the protection of cells against oxidative damage. Plasma glutathione peroxidase has been shown to be a selenium-containing enzyme and the UGA codon is translated into a selenocysteine. A similar protein in rat has been identified as a moonlighting protein based on its ability to serve dual functions as a peroxidase as well as a structural protein in mature spermatozoa. Disruption of this gene in spermatocytes is associated with male infertility. Alternative splicing results in multiple transcript variants. Two pseudogenes of this gene have been defined on chromosomes 10 and 17. [provided by RefSeq, Jan 2014]
Orthologs
Proteins
| phospholipid hydroperoxide glutathione peroxidase, nuclear isoform 1 | |
|---|---|
| Refseq ID | NP_001032830 |
| Protein GI | 90903233 |
| UniProt ID | O70325 |
| mRNA ID | NM_001037741 |
| Length | 253 |
| RefSeq Status | VALIDATED |
| MGRAAARKRGRCRQRGGSPRGRRRRGPGRQSPRKRPGPRRRKARARRRRRARPRRMEPIPEPFNPGPLLQEPPQYCNSSEFLGLCASRDDWRCARSMHEFSAKDIDGHMVCLDKYRGFVCIVTNVASQUGKTDVNYTQLVDLHARYAECGLRILAFPCNQFGRQEPGSNQEIKEFAAGYNVKFDMYSKICVNGDDAHPLWKWMKVQPKGRGMLGNAIKWNFTKFLIDKNGCVVKRYGPMEEPQVIEKDLPCYL | |
| phospholipid hydroperoxide glutathione peroxidase, nuclear isoform 2 precursor | |
|---|---|
| Refseq ID | NP_032188 |
| Protein GI | 90903235 |
| UniProt ID | O70325 |
| mRNA ID | NM_008162 |
| Length | 197 |
| RefSeq Status | VALIDATED |
| MSWGRLSRLLKPALLCGALAAPGLAGTMCASRDDWRCARSMHEFSAKDIDGHMVCLDKYRGFVCIVTNVASQUGKTDVNYTQLVDLHARYAECGLRILAFPCNQFGRQEPGSNQEIKEFAAGYNVKFDMYSKICVNGDDAHPLWKWMKVQPKGRGMLGNAIKWNFTKFLIDKNGCVVKRYGPMEEPQVIEKDLPCYL | |
| sig_peptide: 1..25 inference: COORDINATES: ab initio prediction:SignalP:4.0 calculated_mol_wt: 2566 peptide sequence: MSWGRLSRLLKPALLCGALAAPGLA | |
Gene Information
Gene Ontology (GO Annotations)
| GO ID | Source | Type | Description |
|---|---|---|---|
| GO:0005829 | IDA:MGI | C | cytosol |
| GO:0005743 | IDA:MGI | C | mitochondrial inner membrane |
| GO:0005739 | IDA:MGI | C | mitochondrion |
| GO:0005635 | IDA:MGI | C | nuclear envelope |
| GO:0005634 | IDA:MGI | C | nucleus |
| GO:0004602 | IDA:MGI | F | glutathione peroxidase activity |
| GO:0047066 | IEA:UniProtKB-EC | F | phospholipid-hydroperoxide glutathione peroxidase activity |
| GO:0006325 | IDA:MGI | P | chromatin organization |
| GO:0007275 | IEA:UniProtKB-KW | P | multicellular organismal development |
| GO:0006979 | IEA:InterPro | P | response to oxidative stress |
| GO:0007283 | IDA:MGI | P | spermatogenesis |
Domain Information
UniProt Annotations
Entry Information
Comments
| Comment Type | Description |
|---|---|
| Alternative Products | Event=Alternative splicing, Alternative initiation; Named isoforms=3; Name=Mitochondrial; IsoId=O70325-1; Sequence=Displayed; Name=Nuclear; IsoId=Q91XR9-1; Sequence=External; Name=Cytoplasmic; IsoId=O70325-2; Sequence=VSP_018743; Note=Produced by alternative initiation at Met-28 of isoform Mitochondrial.; |
| Catalytic Activity | 2 glutathione + a lipid hydroperoxide = glutathione disulfide + lipid + 2 H(2)O. |
| Disruption Phenotype | Embryonic lethality. The embryos die after about 7.5 days of development. Causes neurodegeneration. Selective disruption of isoform mitochondrial causes sperm abnormalities and male infertility. {ECO:0000269|PubMed:18762024, ECO:0000269|PubMed:19417079}. |
| Function | Protects cells against membrane lipid peroxidation and cell death. Isoform mitochondrial is required for normal sperm development and male fertility. Could play a major role in protecting mammals from the toxicity of ingested lipid hydroperoxides. Essential for embryonic development. Protects from radiation and oxidative damage. {ECO:0000269|PubMed:12566075, ECO:0000269|PubMed:18762024, ECO:0000269|PubMed:19417079}. |
| Similarity | Belongs to the glutathione peroxidase family. {ECO:0000305}. |
| Subcellular Location | Mitochondrion. Cytoplasm. |
| Subunit | Monomer. {ECO:0000250}. |
| Tissue Specificity | Detected in testis and sperm midpiece (at protein level). Present primarily in testis. {ECO:0000269|PubMed:19417079}. |
Identical and Related Proteins
Unique RefSeq proteins for LMP002781 (as displayed in Record Overview)
| Protein GI | Database | Accession | Length | Protein Name |
|---|---|---|---|---|
| 90903233 | RefSeq | NP_001032830 | 253 | phospholipid hydroperoxide glutathione peroxidase, nuclear isoform 1 |
| 90903235 | RefSeq | NP_032188 | 197 | phospholipid hydroperoxide glutathione peroxidase, nuclear isoform 2 precursor |
Identical Sequences to LMP002781 proteins
| Reference | Database | Accession | Length | Protein Name |
|---|---|---|---|---|
| GI:90903235 | DBBJ | BAC06507.1 | 197 | mitochondrial phospholipid hydroperoxide glutathione peroxidase [Mus musculus] |
| GI:90903233 | DBBJ | BAC06509.1 | 253 | nuclear phospholipid hydroperoxide glutathione peroxidase [Mus musculus] |
| GI:90903235 | DBBJ | BAC55251.1 | 197 | unnamed protein product [Mus musculus] |
| GI:90903233 | DBBJ | BAC87835.1 | 253 | nucleolar phospholipid hydroperoxide glutathione peroxidase [Mus musculus] |
| GI:90903235 | GenBank | AAC15832.1 | 197 | phospholipid hydroperoxide glutathione peroxidase [Mus musculus] |
| GI:90903235 | SwissProt | O70325.4 | 197 | RecName: Full=Phospholipid hydroperoxide glutathione peroxidase, mitochondrial; Short=PHGPx; AltName: Full=Glutathione peroxidase 4; Short=GPx-4; Short=GSHPx-4; Flags: Precursor [Mus musculus] |
Related Sequences to LMP002781 proteins
| Reference | Database | Accession | Length | Protein Name |
|---|---|---|---|---|
| GI:90903235 | DBBJ | BAA22780.1 | 197 | phospholipid hydroperoxide glutathione peroxidase [Mus musculus] |
| GI:90903235 | EMBL | CAD61276.1 | 197 | phospholipid hydroperoxide glutathione peroxidase [Rattus norvegicus] |
| GI:90903233 | EMBL | CAD61278.1 | 253 | phospholipid hydroperoxide glutathione peroxidase [Rattus norvegicus] |
| GI:90903235 | GenBank | AAC52503.2 | 197 | phospholipid hydroperoxide glutathione peroxidase [Rattus norvegicus] |
| GI:90903233 | GenBank | AAK74112.1 | 253 | phospholipid hydroperoxide glutathione peroxidase [Mus musculus] |
| GI:90903233 | GenBank | AAS76675.1 | 253 | sperm nucleus phospholipid-hydroperoxide glutathione peroxidase [Rattus norvegicus] |
| GI:90903233 | RefSeq | NP_001034938.1 | 253 | phospholipid hydroperoxide glutathione peroxidase, nuclear isoform B [Rattus norvegicus] |
| GI:90903235 | RefSeq | NP_058861.3 | 197 | phospholipid hydroperoxide glutathione peroxidase, nuclear isoform A precursor [Rattus norvegicus] |
| GI:90903235 | RefSeq | XP_006978271.1 | 197 | PREDICTED: LOW QUALITY PROTEIN: phospholipid hydroperoxide glutathione peroxidase, mitochondrial [Peromyscus maniculatus bairdii] |
| GI:90903233 | SwissProt | Q91XR8.3 | 253 | RecName: Full=Phospholipid hydroperoxide glutathione peroxidase, nuclear; AltName: Full=Glutathione peroxidase 4; Short=GPx-4; Short=GSHPx-4 [Rattus norvegicus] |
| GI:90903233 | SwissProt | Q91XR9.3 | 253 | RecName: Full=Phospholipid hydroperoxide glutathione peroxidase, nuclear; AltName: Full=Glutathione peroxidase 4; Short=GPx-4; Short=GSHPx-4 [Mus musculus] |
| GI:90903235 | SwissProt | P36970.3 | 197 | RecName: Full=Phospholipid hydroperoxide glutathione peroxidase, mitochondrial; Short=PHGPx; AltName: Full=Glutathione peroxidase 4; Short=GPx-4; Short=GSHPx-4; Flags: Precursor [Rattus norvegicus] |