Gene/Proteome Database (LMPD)

LMPD ID
LMP001878
Gene ID
2879
Species
Homo sapiens (Human)
Gene Name
glutathione peroxidase 4
Gene Symbol
GPX4
Synonyms
GPx-4; GSHPx-4; MCSP; PHGPx; snGPx; snPHGPx
Alternate Names
phospholipid hydroperoxide glutathione peroxidase, mitochondrial; phospholipid hydroperoxidase; sperm nucleus glutathione peroxidase
Chromosome
19
Map Location
19p13.3
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. Human plasma glutathione peroxidase has been shown to be a selenium-containing enzyme and the UGA codon is translated into a selenocysteine. The encoded protein 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. Through alternative splicing and transcription initiation, rat produces proteins that localize to the nucleus, mitochondrion, and cytoplasm. In humans, alternative transcription initiation and the cleavage sites of the mitochondrial and nuclear transit peptides need to be experimentally verified. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2014]
Orthologs
View orthologs and multiple alignments for GPX4

Proteins

phospholipid hydroperoxide glutathione peroxidase, mitochondrial isoform A precursor
Refseq ID NP_002076
Protein GI 75709200
UniProt ID P36969
mRNA ID NM_002085
Length 197
RefSeq Status REVIEWED
MSLGRLCRLLKPALLCGALAAPGLAGTMCASRDDWRCARSMHEFSAKDIDGHMVNLDKYRGFVCIVTNVASQUGKTEVNYTQLVDLHARYAECGLRILAFPCNQFGKQEPGSNEEIKEFAAGYNVKFDMFSKICVNGDDAHPLWKWMKIQPKGKGILGNAIKWNFTKFLIDKNGCVVKRYGPMEEPLVIEKDLPHYF
sig_peptide: 1..25 inference: COORDINATES: ab initio prediction:SignalP:4.0 calculated_mol_wt: 2509 peptide sequence: MSLGRLCRLLKPALLCGALAAPGLA sig_peptide: 1..25 inference: COORDINATES: ab initio prediction:SignalP:4.0 calculated_mol_wt: 2509 peptide sequence: MSLGRLCRLLKPALLCGALAAPGLA
phospholipid hydroperoxide glutathione peroxidase, mitochondrial isoform B precursor
Refseq ID NP_001034936
Protein GI 90903238
UniProt ID P36969
mRNA ID NM_001039847
Length 227
RefSeq Status REVIEWED
MSLGRLCRLLKPALLCGALAAPGLAGTMCASRDDWRCARSMHEFSAKDIDGHMVNLDKYRGFVCIVTNVASQUGKTEVNYTQLVDLHARYAECGLRILAFPCNQFGKQEPGSNEEIKEFAAGYNVKFDMFSKICVNGDDAHPLWKWMKIQPKGKGILGNAIKWNFTKFGHRLSTVPHRQERLRGEALRTHGGAPGDREGPAPLFLAPQVCGPARAPAHALGAFHRHS
phospholipid hydroperoxide glutathione peroxidase, mitochondrial isoform C precursor
Refseq ID NP_001034937
Protein GI 90903240
UniProt ID Q6PI42
mRNA ID NM_001039848
Length 234
RefSeq Status REVIEWED
MGRAGAGSPGRRRQRCQSRGRRRPRAPRRRKAPACRRRRARRRRKKPCPRSLRPEIHECPKSQDPCASRDDWRCARSMHEFSAKDIDGHMVNLDKYRGFVCIVTNVASQUGKTEVNYTQLVDLHARYAECGLRILAFPCNQFGKQEPGSNEEIKEFAAGYNVKFDMFSKICVNGDDAHPLWKWMKIQPKGKGILGNAIKWNFTKFLIDKNGCVVKRYGPMEEPLVIEKDLPHYF

Gene Information

Entrez Gene ID
2879
Gene Name
glutathione peroxidase 4
Gene Symbol
GPX4
Species
Homo sapiens

Gene Ontology (GO Annotations)

GO ID Source Type Description
GO:0005829 TAS:Reactome C cytosol
GO:0070062 IDA:UniProt C extracellular vesicular exosome
GO:0005743 IEA:Ensembl C mitochondrial inner membrane
GO:0005739 TAS:UniProtKB C mitochondrion
GO:0005635 IEA:Ensembl C nuclear envelope
GO:0005634 IDA:UniProt C nucleus
GO:0043295 IEA:Ensembl F glutathione binding
GO:0004602 TAS:UniProtKB F glutathione peroxidase activity
GO:0047066 IEA:UniProtKB-EC F phospholipid-hydroperoxide glutathione peroxidase activity
GO:0008430 IEA:Ensembl F selenium binding
GO:0007568 IEA:Ensembl P aging
GO:0019369 TAS:Reactome P arachidonic acid metabolic process
GO:0006325 IEA:Ensembl P chromatin organization
GO:0006749 IEA:Ensembl P glutathione metabolic process
GO:0042744 IEA:Ensembl P hydrogen peroxide catabolic process
GO:0019372 TAS:Reactome P lipoxygenase pathway
GO:0007275 IEA:UniProtKB-KW P multicellular organismal development
GO:0055114 TAS:UniProtKB P oxidation-reduction process
GO:0006644 TAS:UniProtKB P phospholipid metabolic process
GO:0050727 IEA:Ensembl P regulation of inflammatory response
GO:0032355 IEA:Ensembl P response to estradiol
GO:0044281 TAS:Reactome P small molecule metabolic process
GO:0007283 IEA:Ensembl P spermatogenesis

REACTOME Pathway Links

REACTOME Pathway ID Description
REACT_150201 Synthesis of 12-eicosatetraenoic acid derivatives
REACT_150422 Synthesis of 15-eicosatetraenoic acid derivatives
REACT_150209 Synthesis of 5-eicosatetraenoic acids

Domain Information

InterPro Annotations

Accession Description
IPR000889 Glutathione peroxidase
IPR029759 Glutathione peroxidase active site
IPR029760 Glutathione peroxidase conserved site
IPR012336 Thioredoxin-like fold

UniProt Annotations

Entry Information

Gene Name
glutathione peroxidase 4
Protein Entry
Q6PI42_HUMAN
UniProt ID
Q6PI42
Species
Human

Comments

Comment Type Description
Alternative Products Event=Alternative initiation; Named isoforms=2; Name=Mitochondrial; IsoId=P36969-1; Sequence=Displayed; Name=Cytoplasmic; IsoId=P36969-2; Sequence=VSP_018740;
Catalytic Activity 2 glutathione + a lipid hydroperoxide = glutathione disulfide + lipid + 2 H(2)O.
Disease Spondylometaphyseal dysplasia, Sedaghatian type (SMDS) [MIM
Function Protects cells against membrane lipid peroxidation and cell death. 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 (By similarity).
Similarity Belongs to the glutathione peroxidase family.
Subcellular Location Isoform Cytoplasmic: Cytoplasm.
Subcellular Location Isoform Mitochondrial: Mitochondrion.
Subunit Monomer. Has a tendency to form higher mass oligomers.
Tissue Specificity Present primarily in testis.
Web Resource Name=NIEHS-SNPs; URL="http://egp.gs.washington.edu/data/gpx4/";

Identical and Related Proteins

Unique RefSeq proteins for LMP001878 (as displayed in Record Overview)

Protein GI Database Accession Length Protein Name
75709200 RefSeq NP_002076 197 phospholipid hydroperoxide glutathione peroxidase, mitochondrial isoform A precursor
90903238 RefSeq NP_001034936 227 phospholipid hydroperoxide glutathione peroxidase, mitochondrial isoform B precursor
90903240 RefSeq NP_001034937 234 phospholipid hydroperoxide glutathione peroxidase, mitochondrial isoform C precursor

Identical Sequences to LMP001878 proteins

Reference Database Accession Length Protein Name
GI:75709200 DBBJ BAE17018.1 197 glutathione peroxidase 4 [Pongo pygmaeus]
GI:75709200 GenBank AAC03239.1 197 GSHH_HUMAN [Homo sapiens]
GI:75709200 GenBank AAC32261.1 197 selenium-dependent phospholipid hydroperoxide glutathione peroxidase [Homo sapiens]
GI:75709200 GenBank AAP72965.1 197 glutathione peroxidase 4 (phospholipid hydroperoxidase) [Homo sapiens]
GI:75709200 SwissProt P36969.3 197 RecName: Full=Phospholipid hydroperoxide glutathione peroxidase, mitochondrial; Short=PHGPx; AltName: Full=Glutathione peroxidase 4; Short=GPx-4; Short=GSHPx-4; Flags: Precursor [Homo sapiens]
GI:75709200 SwissProt Q4AEH2.2 197 RecName: Full=Phospholipid hydroperoxide glutathione peroxidase, mitochondrial; Short=PHGPx; AltName: Full=Glutathione peroxidase 4; Short=GPx-4; Short=GSHPx-4; Flags: Precursor [Pongo pygmaeus]

Related Sequences to LMP001878 proteins

Reference Database Accession Length Protein Name
GI:90903240 DBBJ BAC06509.1 253 nuclear phospholipid hydroperoxide glutathione peroxidase [Mus musculus]
GI:75709200 EMBL CAA50793.1 197 phospholipid hydroperoxide glutathione peroxidase [Homo sapiens]
GI:90903238 EMBL CAA50793.1 197 phospholipid hydroperoxide glutathione peroxidase [Homo sapiens]
GI:90903238 GenBank AAH11836.1 197 Glutathione peroxidase 4 (phospholipid hydroperoxidase) [Homo sapiens]
GI:75709200 GenBank AAH11836.1 197 Glutathione peroxidase 4 (phospholipid hydroperoxidase) [Homo sapiens]
GI:75709200 GenBank AAH39849.1 197 Glutathione peroxidase 4 (phospholipid hydroperoxidase) [Homo sapiens]
GI:90903238 GenBank AAH39849.1 197 Glutathione peroxidase 4 (phospholipid hydroperoxidase) [Homo sapiens]
GI:75709200 GenBank AAH21567.1 197 Glutathione peroxidase 4 (phospholipid hydroperoxidase) [Homo sapiens]
GI:90903238 GenBank ACM80670.1 197 Sequence 6168 from patent US 6812339
GI:75709200 GenBank ACM80670.1 197 Sequence 6168 from patent US 6812339
GI:75709200 GenBank AHD72833.1 197 Sequence 9901 from patent US 8586006
GI:90903238 GenBank AHD72833.1 197 Sequence 9901 from patent US 8586006
GI:90903240 RefSeq XP_006050558.1 240 PREDICTED: LOW QUALITY PROTEIN: phospholipid hydroperoxide glutathione peroxidase, nuclear [Bubalus bubalis]
GI:90903240 RefSeq XP_007992765.1 381 PREDICTED: LOW QUALITY PROTEIN: phospholipid hydroperoxide glutathione peroxidase, mitochondrial [Chlorocebus sabaeus]
GI:90903240 RefSeq XP_008586242.1 320 PREDICTED: LOW QUALITY PROTEIN: phospholipid hydroperoxide glutathione peroxidase, mitochondrial-like [Galeopterus variegatus]
GI:90903238 RefSeq XP_008964608.1 227 PREDICTED: LOW QUALITY PROTEIN: phospholipid hydroperoxide glutathione peroxidase, mitochondrial [Pan paniscus]
GI:90903240 RefSeq XP_008985133.1 234 PREDICTED: LOW QUALITY PROTEIN: phospholipid hydroperoxide glutathione peroxidase, mitochondrial [Callithrix jacchus]
GI:90903240 RefSeq XP_009191277.1 234 PREDICTED: LOW QUALITY PROTEIN: phospholipid hydroperoxide glutathione peroxidase, mitochondrial [Papio anubis]