Gpx4 glutathione peroxidase 4 [Mus musculus (house mouse)] - Gene

Summary

Official Symbol: Gpx4provided by MGI
Official Full Name: glutathione peroxidase 4provided by MGI
Primary source: MGI:MGI:104767
See related: Ensembl:ENSMUSG00000075706 AllianceGenome:MGI:104767
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Mus musculus
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; Murinae; Mus; Mus
Also known as: GPx-4; PHGPx; snGPx; GSHPx-4; mtPHGPx
Summary: 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. Transcript variants resulting from alternative splicing or use of alternate promoters have been described to encode isoforms with different subcellular localization. Pseudogenes of this locus have been identified on chromosomes 10 and 17. [provided by RefSeq, Jan 2019]
Expression: Ubiquitous expression in testis adult (RPKM 772.1), kidney adult (RPKM 308.6) and 28 other tissues See more
Orthologs: human all
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Genomic context

Location:: 10 C1; 10 39.72 cM

Exon count:: 10

Annotation release	Status	Assembly	Chr	Location
RS_2024_02	current	GRCm39 (GCF_000001635.27)	10	NC_000076.7 (79883000..79892273)
108.20200622	previous assembly	GRCm38.p6 (GCF_000001635.26)	10	NC_000076.6 (80047166..80056439)

Chromosome 10 - NC_000076.7 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: Mouse ENCODE transcriptome data
Description: RNA profiling data sets generated by the Mouse ENCODE project.
BioProject: PRJNA66167
Publication: PMID 25409824
Analysis date: n/a

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Gpx4 Regulates Invariant NKT Cell Homeostasis and Function by Preventing Lipid Peroxidation and Ferroptosis.
Title: Gpx4 Regulates Invariant NKT Cell Homeostasis and Function by Preventing Lipid Peroxidation and Ferroptosis.
METTL14 promotes chondrocyte ferroptosis in osteoarthritis via m6A modification of GPX4.
Title: METTL14 promotes chondrocyte ferroptosis in osteoarthritis via m6A modification of GPX4.
Brown adipose tissue-derived exosomes improve polycystic ovary syndrome in mice via STAT3/GPX4 signaling pathway.
Title: Brown adipose tissue-derived exosomes improve polycystic ovary syndrome in mice via STAT3/GPX4 signaling pathway.
GPX4 restricts ferroptosis of NKp46[+]ILC3s to control intestinal inflammation.
Title: GPX4 restricts ferroptosis of NKp46(+)ILC3s to control intestinal inflammation.
GDF15 attenuates sepsis-induced myocardial dysfunction by inhibiting cardiomyocytes ferroptosis via the SOCS1/GPX4 signaling pathway.
Title: GDF15 attenuates sepsis-induced myocardial dysfunction by inhibiting cardiomyocytes ferroptosis via the SOCS1/GPX4 signaling pathway.
Dipeptidase 1 promotes ferroptosis in renal tubular epithelial cells in diabetic nephropathy via inhibition of the GSH/GPX4 axis.
Title: Dipeptidase 1 promotes ferroptosis in renal tubular epithelial cells in diabetic nephropathy via inhibition of the GSH/GPX4 axis.
USP8-governed GPX4 homeostasis orchestrates ferroptosis and cancer immunotherapy.
Title: USP8-governed GPX4 homeostasis orchestrates ferroptosis and cancer immunotherapy.
Silent information regulator sirtuin 1 ameliorates acute liver failure via the p53/glutathione peroxidase 4/gasdermin D axis.
Title: Silent information regulator sirtuin 1 ameliorates acute liver failure via the p53/glutathione peroxidase 4/gasdermin D axis.
Anti-aging Factor GRSF1 Attenuates Cerebral Ischemia-Reperfusion Injury in Mice by Inhibiting GPX4-Mediated Ferroptosis.
Title: Anti-aging Factor GRSF1 Attenuates Cerebral Ischemia-Reperfusion Injury in Mice by Inhibiting GPX4-Mediated Ferroptosis.
GPX4-mediated bone ferroptosis under mechanical stress decreased bone formation via the YAP-TEAD signalling pathway.
Title: GPX4-mediated bone ferroptosis under mechanical stress decreased bone formation via the YAP-TEAD signalling pathway.

Submit: New GeneRIF Correction See all GeneRIFs (107)

Variation

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Alleles

Alleles of this type are documented at Mouse Genome Informatics (MGI)

Endonuclease-mediated (6)
Targeted (13) 1 citation

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

Gpx4 (e-PCR), detects polymorphism
- UniSTS:527369

RH125284 (e-PCR)
- UniSTS:162106

Gpx4 (e-PCR), detects polymorphism
- UniSTS:532337

Gpx4 (e-PCR), detects polymorphism
- UniSTS:532338

Gpx4 (e-PCR), detects polymorphism
- UniSTS:532339

Gpx4 (e-PCR), detects polymorphism
- UniSTS:532340

Gpx4 (e-PCR), detects polymorphism
- UniSTS:532341

UniSTS:237712 (e-PCR)
- UniSTS:237712

Gpx4 (e-PCR), detects polymorphism
- UniSTS:516559

RH137289 (e-PCR)
- UniSTS:219377

Gene Ontology Provided by MGI

Function	Evidence Code	Pubs
enables glutathione peroxidase activity	IBA Inferred from Biological aspect of Ancestor more info
enables glutathione peroxidase activity	IDA Inferred from Direct Assay more info	PubMed
enables glutathione peroxidase activity	ISO Inferred from Sequence Orthology more info	PubMed
enables identical protein binding	IEA Inferred from Electronic Annotation more info
enables identical protein binding	ISO Inferred from Sequence Orthology more info
enables phospholipid-hydroperoxide glutathione peroxidase activity	IBA Inferred from Biological aspect of Ancestor more info
enables phospholipid-hydroperoxide glutathione peroxidase activity	IDA Inferred from Direct Assay more info	PubMed
enables phospholipid-hydroperoxide glutathione peroxidase activity	ISO Inferred from Sequence Orthology more info
enables selenium binding	IEA Inferred from Electronic Annotation more info
enables selenium binding	ISO Inferred from Sequence Orthology more info

Process	Evidence Code	Pubs
acts_upstream_of_or_within apoptotic process	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in arachidonate metabolic process	ISO Inferred from Sequence Orthology more info
involved_in arachidonate metabolic process	ISS Inferred from Sequence or Structural Similarity more info
involved_in cellular oxidant detoxification	IEA Inferred from Electronic Annotation more info
acts_upstream_of_or_within cerebellum development	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within chromatin organization	IDA Inferred from Direct Assay more info	PubMed
acts_upstream_of_or_within dendrite development	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in lipoxygenase pathway	ISO Inferred from Sequence Orthology more info
involved_in lipoxygenase pathway	ISS Inferred from Sequence or Structural Similarity more info
acts_upstream_of_or_within multicellular organism growth	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in negative regulation of ferroptosis	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in protein polymerization	IEA Inferred from Electronic Annotation more info
involved_in protein polymerization	ISO Inferred from Sequence Orthology more info
involved_in response to estradiol	IEA Inferred from Electronic Annotation more info
acts_upstream_of_or_within response to lipopolysaccharide	IDA Inferred from Direct Assay more info	PubMed
involved_in response to oxidative stress	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within spermatogenesis	IDA Inferred from Direct Assay more info	PubMed
involved_in spermatogenesis	IMP Inferred from Mutant Phenotype more info	PubMed

Component	Evidence Code	Pubs
located_in cytosol	IDA Inferred from Direct Assay more info	PubMed
located_in cytosol	ISO Inferred from Sequence Orthology more info
located_in mitochondrial inner membrane	HDA more info	PubMed
located_in mitochondrion	HDA more info	PubMed
is_active_in mitochondrion	IBA Inferred from Biological aspect of Ancestor more info
located_in mitochondrion	IDA Inferred from Direct Assay more info	PubMed
located_in nuclear envelope	IDA Inferred from Direct Assay more info	PubMed
is_active_in nucleus	IBA Inferred from Biological aspect of Ancestor more info
located_in nucleus	IDA Inferred from Direct Assay more info	PubMed
part_of protein-containing complex	IEA Inferred from Electronic Annotation more info
part_of protein-containing complex	ISO Inferred from Sequence Orthology more info

General protein information

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Preferred Names: phospholipid hydroperoxide glutathione peroxidase GPX4

Names: phospholipid hydroperoxide glutathione peroxidase, mitochondrial; phospholipid hydroperoxide glutathione peroxidase, nuclear; sperm nuclei glutathione peroxidase

NP_001032830.2

EC 1.11.1.12

EC 1.11.1.9

NP_001354924.1

EC 1.11.1.12

EC 1.11.1.9

NP_032188.3

EC 1.11.1.12

EC 1.11.1.9

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

mRNA and Protein(s)

NM_001037741.4 → NP_001032830.2 phospholipid hydroperoxide glutathione peroxidase GPX4 isoform B

See identical proteins and their annotated locations for NP_001032830.2

Status: REVIEWED

Description

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).

Source sequence(s)

AC159999, AK006441, CX733872

Consensus CDS

CCDS24007.1

UniProtKB/TrEMBL

Q76LV0

Related

ENSMUSP00000094863.5, ENSMUST00000097227.11

Conserved Domains (1) summary

cd00340
Location:96 → 249

GSH_Peroxidase; Glutathione (GSH) peroxidase family; tetrameric selenoenzymes that catalyze the reduction of a variety of hydroperoxides including lipid peroxidases, using GSH as a specific electron donor substrate. GSH peroxidase contains one selenocysteine residue per ...
NM_001367995.1 → NP_001354924.1 phospholipid hydroperoxide glutathione peroxidase GPX4 isoform C

Status: REVIEWED

Description

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).

Source sequence(s)

AK006441, CX733872

UniProtKB/TrEMBL

Q3TI34, Q5XJZ8

Related

ENSMUSP00000138186.3, ENSMUST00000183037.3
NM_008162.4 → NP_032188.3 phospholipid hydroperoxide glutathione peroxidase GPX4 isoform A precursor

See identical proteins and their annotated locations for NP_032188.3

Status: REVIEWED

Description

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).

Source sequence(s)

AK006441, BY238083, CX733872

Consensus CDS

CCDS35973.1

UniProtKB/Swiss-Prot

O35560, O70325, Q8K4U8, Q91XR9, Q9JK35

UniProtKB/TrEMBL

Q3TIF2

Related

ENSMUSP00000101011.3, ENSMUST00000105372.9

Conserved Domains (1) summary

cd00340
Location:40 → 193

GSH_Peroxidase; Glutathione (GSH) peroxidase family; tetrameric selenoenzymes that catalyze the reduction of a variety of hydroperoxides including lipid peroxidases, using GSH as a specific electron donor substrate. GSH peroxidase contains one selenocysteine residue per ...

RNA

NR_110342.1 RNA Sequence

Status: REVIEWED

Description

Transcript Variant: This variant (3) contains alternate 5' terminal exons and lacks an internal exon compared to variant 1. This variant is represented as non-coding because the predicted protein does not meet RefSeq quality criteria.

Source sequence(s)

AA510431, AK145770

Related

ENSMUST00000144698.8