Gpx4 glutathione peroxidase 4 [Rattus norvegicus (Norway rat)] - Gene

Summary

Official Symbol: Gpx4provided by RGD
Official Full Name: glutathione peroxidase 4provided by RGD
Primary source: RGD:69226
See related: EnsemblRapid:ENSRNOG00000013604 AllianceGenome:RGD:69226
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Rattus norvegicus
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; Murinae; Rattus
Also known as: Phgpx; gpx-4; snGpx; Gshpx-4
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 1, 10 and 14. [provided by RefSeq, Jan 2019]
Expression: Biased expression in Testes (RPKM 2739.4), Adrenal (RPKM 1410.3) and 9 other tissues See more
Orthologs: human mouse all
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Genomic context

Location:: 7q11

Exon count:: 8

Annotation release	Status	Assembly	Chr	Location
RS_2024_02	current	GRCr8 (GCF_036323735.1)	7	NC_086025.1 (10300833..10303629, complement)
RS_2023_06	previous assembly	mRatBN7.2 (GCF_015227675.2)	7	NC_051342.1 (9650186..9652982, complement)
106	previous assembly	Rnor_6.0 (GCF_000001895.5)	7	NC_005106.4 (12516357..12519154, complement)

Chromosome 7 - NC_086025.1 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: A rat RNA-Seq transcriptomic BodyMap across 11 organs and 4 developmental stages
Description: 320 RNA samples isolated from 11 organs (adrenal gland, brain, heart, kidney, liver, lung, muscle, spleen, thymus, and testes or uterus) from both sexes of Fischer 344 rats across four developmental stages (2-, 6-, 21-, and 104-weeks-old)
BioProject: PRJNA238328
Publication: PMID 24510058
Analysis date: Mon Jun 6 17:44:12 2016

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

The role and possible mechanism of the ferroptosis-related SLC7A11/GSH/GPX4 pathway in myocardial ischemia-reperfusion injury.
Title: The role and possible mechanism of the ferroptosis-related SLC7A11/GSH/GPX4 pathway in myocardial ischemia-reperfusion injury.
METTL14 promotes chondrocyte ferroptosis in osteoarthritis via m6A modification of GPX4.
Title: METTL14 promotes chondrocyte ferroptosis in osteoarthritis via m6A modification of GPX4.
BCAT1 alleviates early brain injury by inhibiting ferroptosis through PI3K/AKT/mTOR/GPX4 pathway after subarachnoid hemorrhage.
Title: BCAT1 alleviates early brain injury by inhibiting ferroptosis through PI3K/AKT/mTOR/GPX4 pathway after subarachnoid hemorrhage.
Platelet-derived exosomes alleviate tendon stem/progenitor cell senescence and ferroptosis by regulating AMPK/Nrf2/GPX4 signaling and improve tendon-bone junction regeneration in rats.
Title: Platelet-derived exosomes alleviate tendon stem/progenitor cell senescence and ferroptosis by regulating AMPK/Nrf2/GPX4 signaling and improve tendon-bone junction regeneration in rats.
Glutathione peroxidase 4 restrains temporomandibular joint osteoarthritis progression by inhibiting ferroptosis.
Title: Glutathione peroxidase 4 restrains temporomandibular joint osteoarthritis progression by inhibiting ferroptosis.
Targeting GPX4-mediated Ferroptosis Alleviates Liver Steatosis in a Rat Model of Total Parenteral Nutrition.
Title: Targeting GPX4-mediated Ferroptosis Alleviates Liver Steatosis in a Rat Model of Total Parenteral Nutrition.
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.
Magnetic graphene oxide nanocomposites induce cytotoxicity in ADSCs via GPX4 regulating ferroptosis.
Title: Magnetic graphene oxide nanocomposites induce cytotoxicity in ADSCs via GPX4 regulating ferroptosis.
Guanine-rich RNA sequence binding factor 1 regulates neuronal ferroptosis after spinal cord injury in rats via the GPX4 signaling pathway.
Title: Guanine-rich RNA sequence binding factor 1 regulates neuronal ferroptosis after spinal cord injury in rats via the GPX4 signaling pathway.
Acid sphingomyelinase mediates ferroptosis induced by high glucose via autophagic degradation of GPX4 in type 2 diabetic osteoporosis.
Title: Acid sphingomyelinase mediates ferroptosis induced by high glucose via autophagic degradation of GPX4 in type 2 diabetic osteoporosis.

Submit: New GeneRIF Correction See all GeneRIFs (39)

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

RH143516 (e-PCR)
- UniSTS:232762

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

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

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

RH137289 (e-PCR)
- UniSTS:219377

Gene Ontology Provided by RGD

Function	Evidence Code	Pubs
enables glutathione peroxidase activity	IBA Inferred from Biological aspect of Ancestor more info
enables glutathione peroxidase activity	ISO Inferred from Sequence Orthology more info
enables glutathione peroxidase activity	ISS Inferred from Sequence or Structural Similarity 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	IDA Inferred from Direct Assay more info	PubMed

Process	Evidence Code	Pubs
acts_upstream_of_or_within apoptotic process	ISO Inferred from Sequence Orthology more info
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	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within chromatin organization	ISO Inferred from Sequence Orthology more info
involved_in chromatin organization	ISS Inferred from Sequence or Structural Similarity more info
acts_upstream_of_or_within dendrite development	ISO Inferred from Sequence Orthology more info
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	ISO Inferred from Sequence Orthology more info
involved_in negative regulation of ferroptosis	ISO Inferred from Sequence Orthology more info
involved_in negative regulation of ferroptosis	ISS Inferred from Sequence or Structural Similarity more info
involved_in protein polymerization	ISO Inferred from Sequence Orthology more info
involved_in response to estradiol	IEP Inferred from Expression Pattern more info	PubMed
acts_upstream_of_or_within response to lipopolysaccharide	ISO Inferred from Sequence Orthology more info
involved_in response to oxidative stress	ISO Inferred from Sequence Orthology more info
involved_in response to oxidative stress	ISS Inferred from Sequence or Structural Similarity more info
acts_upstream_of_or_within spermatogenesis	ISO Inferred from Sequence Orthology more info
involved_in spermatogenesis	ISO Inferred from Sequence Orthology more info
involved_in spermatogenesis	ISS Inferred from Sequence or Structural Similarity more info

Component	Evidence Code	Pubs
is_active_in cytosol	IDA Inferred from Direct Assay more info	PubMed
located_in cytosol	ISO Inferred from Sequence Orthology more info
located_in cytosol	ISS Inferred from Sequence or Structural Similarity more info
is_active_in mitochondrion	IBA Inferred from Biological aspect of Ancestor more info
is_active_in mitochondrion	IDA Inferred from Direct Assay more info	PubMed
located_in mitochondrion	ISO Inferred from Sequence Orthology more info
located_in nuclear envelope	ISO Inferred from Sequence Orthology more info
located_in nucleolus	IEA Inferred from Electronic Annotation more info
is_active_in nucleus	IBA Inferred from Biological aspect of Ancestor more info
located_in nucleus	ISO Inferred from Sequence Orthology more info
located_in nucleus	ISS Inferred from Sequence or Structural Similarity 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

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

NP_001034938.1

EC 1.11.1.12

EC 1.11.1.9

NP_001354972.1

EC 1.11.1.12

EC 1.11.1.9

NP_058861.3

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_001039849.3 → NP_001034938.1 phospholipid hydroperoxide glutathione peroxidase isoform B

See identical proteins and their annotated locations for NP_001034938.1

Status: REVIEWED

Description

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. This isoform has been reported to be localized in the sperm nucleus (PMID:11344099).

Source sequence(s)

JAXUCZ010000007

UniProtKB/Swiss-Prot

P36970

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_001368043.1 → NP_001354972.1 phospholipid hydroperoxide glutathione peroxidase isoform C

Status: REVIEWED

Description

Transcript Variant: This variant (3) 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, also known as the S-form) has a shorter N-terminus compared to isoform A and is localized in the cytoplasm (PMIDs:7592947, 9988735).

Source sequence(s)

JAXUCZ010000007
NM_017165.4 → NP_058861.3 phospholipid hydroperoxide glutathione peroxidase isoform A precursor

See identical proteins and their annotated locations for NP_058861.3

Status: REVIEWED

Description

Transcript Variant: This variant (1) represents the predominant transcript and encodes the canonical isoform A (also known as phGPx or the L-form), which is localized to the mitochondria (PMID:9988735).

Source sequence(s)

JAXUCZ010000007

UniProtKB/Swiss-Prot

P36970, Q6PZ55, Q76LU9, Q91XR8

Related

ENSRNOP00000076198.1, ENSRNOT00000093376.3

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 ...