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GPX4 glutathione peroxidase 4 [ Homo sapiens (human) ]

Gene ID: 2879, updated on 26-Sep-2021

Summary

Official Symbol
GPX4provided by HGNC
Official Full Name
glutathione peroxidase 4provided by HGNC
Primary source
HGNC:HGNC:4556
See related
Ensembl:ENSG00000167468 MIM:138322
Gene type
protein coding
RefSeq status
REVIEWED
Organism
Homo sapiens
Lineage
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as
MCSP; SMDS; GPx-4; PHGPx; snGPx; GSHPx-4; snPHGPx
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. Mutations in this gene are associated with Sedaghatian type of spondylometaphyseal dysplasia (SMDS). 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. [provided by RefSeq, Dec 2018]
Expression
Broad expression in fat (RPKM 347.9), testis (RPKM 229.8) and 24 other tissues See more
Orthologs
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Genomic context

See GPX4 in Genome Data Viewer
Location:
19p13.3
Exon count:
8
Annotation release Status Assembly Chr Location
109.20210514 current GRCh38.p13 (GCF_000001405.39) 19 NC_000019.10 (1103994..1106779)
105.20201022 previous assembly GRCh37.p13 (GCF_000001405.25) 19 NC_000019.9 (1103993..1106778)

Chromosome 19 - NC_000019.10Genomic Context describing neighboring genes Neighboring gene ATP binding cassette subfamily A member 7 Neighboring gene Rho GTPase activating protein 45 Neighboring gene RNA polymerase II, I and III subunit E Neighboring gene strawberry notch homolog 2 Neighboring gene uncharacterized LOC102723798 Neighboring gene collagen alpha-1(VII) chain Neighboring gene SBNO2 intron CAGE-defined low expression enhancer

Genomic regions, transcripts, and products

Expression

  • Project title: HPA RNA-seq normal tissues
  • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
  • BioProject: PRJEB4337
  • Publication: PMID 24309898
  • Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Phenotypes

Associated conditions

Description Tests
Genome-wide meta-analysis increases to 71 the number of confirmed Crohn's disease susceptibility loci.
GeneReviews: Not available
Host-microbe interactions have shaped the genetic architecture of inflammatory bowel disease.
GeneReviews: Not available
Spondylometaphyseal dysplasia, Sedaghatian type
MedGen: C1855229 OMIM: 250220 GeneReviews: Not available
Compare labs

HIV-1 interactions

Replication interactions

Interaction Pubs
Knockdown of glutathione peroxidase 4 (GPX4) by shRNA library screening inhibits HIV-1 replication in cultured Jurkat T-cells PubMed

Protein interactions

Protein Gene Interaction Pubs
Tat tat HIV-1 Tat causes a greater than 50% decrease in intracellular reduced glutathione (GSH), leading to the extracellular appearance of acidic FGF-1, an effect that is partially mediated through modulation of GSH biosynthetic enzymes PubMed
tat Expression of HIV-1 Tat in HeLa cells downregulates cytoplasmic glutathione peroxidase while upregulating phospholipid hydroperoxide glutathione peroxidase, thereby deregulating intracellular oxidant/antioxidant balance and amplifying UV sensitivity PubMed

Go to the HIV-1, Human Interaction Database

Pathways from PubChem

Interactions

Products Interactant Other Gene Complex Source Pubs Description

General gene information

Markers

Homology

Gene Ontology Provided by GOA

Function Evidence Code Pubs
enables glutathione peroxidase activity IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
enables glutathione peroxidase activity IMP
Inferred from Mutant Phenotype
more info
PubMed 
enables identical protein binding IMP
Inferred from Mutant Phenotype
more info
PubMed 
enables peroxidase activity IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
enables phospholipid-hydroperoxide glutathione peroxidase activity IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
enables phospholipid-hydroperoxide glutathione peroxidase activity IDA
Inferred from Direct Assay
more info
PubMed 
enables phospholipid-hydroperoxide glutathione peroxidase activity ISS
Inferred from Sequence or Structural Similarity
more info
 
enables phospholipid-hydroperoxide glutathione peroxidase activity TAS
Traceable Author Statement
more info
 
enables protein binding IPI
Inferred from Physical Interaction
more info
PubMed 
enables selenium binding IEA
Inferred from Electronic Annotation
more info
 
Process Evidence Code Pubs
involved_in aging IEA
Inferred from Electronic Annotation
more info
 
involved_in arachidonic acid metabolic process IDA
Inferred from Direct Assay
more info
PubMed 
involved_in cellular oxidant detoxification IEA
Inferred from Electronic Annotation
more info
 
involved_in chromatin organization IEA
Inferred from Electronic Annotation
more info
 
involved_in glutathione metabolic process IEA
Inferred from Electronic Annotation
more info
 
involved_in lipoxygenase pathway IDA
Inferred from Direct Assay
more info
PubMed 
involved_in long-chain fatty acid biosynthetic process TAS
Traceable Author Statement
more info
 
involved_in negative regulation of ferroptosis ISS
Inferred from Sequence or Structural Similarity
more info
 
involved_in phospholipid metabolic process TAS
Traceable Author Statement
more info
PubMed 
involved_in protein polymerization IMP
Inferred from Mutant Phenotype
more info
PubMed 
involved_in regulation of inflammatory response IEA
Inferred from Electronic Annotation
more info
 
involved_in response to estradiol IEA
Inferred from Electronic Annotation
more info
 
involved_in response to oxidative stress ISS
Inferred from Sequence or Structural Similarity
more info
 
involved_in spermatogenesis ISS
Inferred from Sequence or Structural Similarity
more info
 
Component Evidence Code Pubs
located_in cytosol IDA
Inferred from Direct Assay
more info
PubMed 
located_in cytosol TAS
Traceable Author Statement
more info
 
located_in extracellular exosome HDA PubMed 
is_active_in mitochondrion IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
located_in nuclear envelope IEA
Inferred from Electronic Annotation
more info
 
located_in nucleus HDA PubMed 
is_active_in nucleus IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
part_of protein-containing complex IMP
Inferred from Mutant Phenotype
more info
PubMed 

General protein information

Preferred Names
phospholipid hydroperoxide glutathione peroxidase
Names
epididymis secretory sperm binding protein
phospholipid hydroperoxidase
phospholipid hydroperoxide glutathione peroxidase, mitochondrial
selenoprotein GPX4
sperm nucleus glutathione peroxidase
NP_001034936.1
NP_001034937.1
NP_001354761.1
NP_002076.2

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.

Genomic

  1. NG_050621.1 RefSeqGene

    Range
    5069..7854
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. NM_001039847.3NP_001034936.1  phospholipid hydroperoxide glutathione peroxidase isoform B precursor

    Status: REVIEWED

    Description
    Transcript Variant: This variant (2) uses an alternate acceptor splice site in the 3' coding region, which causes a frame-shift, compared to variant 1. The resulting isoform (B) has a longer and a distinct C-terminus compared to isoform A.
    Source sequence(s)
    AL558552, BC039849
    UniProtKB/Swiss-Prot
    P36969
    Conserved Domains (1) summary
    cd00340
    Location:40168
    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 ...
  2. NM_001039848.4NP_001034937.1  phospholipid hydroperoxide glutathione peroxidase isoform C

    Status: REVIEWED

    Description
    Transcript Variant: This variant (3) contains an alternate 5' terminal exon compared to variant 1. The resulting isoform (C) 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)
    BC021567, BF740029, BM764133
    UniProtKB/TrEMBL
    Q6PI42
    Related
    ENSP00000477503.1, ENST00000622390.4
    Conserved Domains (1) summary
    cd00340
    Location:77230
    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 ...
  3. NM_001367832.1NP_001354761.1  phospholipid hydroperoxide glutathione peroxidase isoform D

    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 (D) 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)
    BC039849
    Related
    ENSP00000483655.1, ENST00000611653.4
  4. NM_002085.5NP_002076.2  phospholipid hydroperoxide glutathione peroxidase isoform A precursor

    See identical proteins and their annotated locations for NP_002076.2

    Status: REVIEWED

    Description
    Transcript Variant: This variant (1) represents the predominant transcript and encodes the canonical isoform A. A similar isoform in rat (L-form) has been shown to be localized to the mitochondria (PMID:9988735).
    Source sequence(s)
    BC039849
    Consensus CDS
    CCDS42457.1
    UniProtKB/Swiss-Prot
    P36969
    Related
    ENSP00000346103.7, ENST00000354171.13
    Conserved Domains (1) summary
    cd00340
    Location:40193
    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 ...

RefSeqs of Annotated Genomes: Homo sapiens Updated Annotation Release 109.20210514

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p13 Primary Assembly

Genomic

  1. NC_000019.10 Reference GRCh38.p13 Primary Assembly

    Range
    1103994..1106779
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)
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