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Protein

Phospholipid hydroperoxide glutathione peroxidase, mitochondrial

Gene

Gpx4

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Protects cells against membrane lipid peroxidation and cell death (PubMed:12566075). Required for normal sperm development and male fertility (PubMed:19417079). Could play a major role in protecting mammals from the toxicity of ingested lipid hydroperoxides. Essential for embryonic development (PubMed:12566075). Protects from radiation and oxidative damage (PubMed:12566075). Essential for maturation and survival of photoreceptor cells (PubMed:22207760). Plays a role in a primary T cell response to viral and parasitic infection by protecting T cells from ferroptosis, a cell death resulting from an iron-dependent accumulation of lipid reactive oxygen species, and by supporting T cell expansion (PubMed:25824823).5 Publications

Catalytic activityi

2 glutathione + a hydroperoxy-fatty-acyl-[lipid] = glutathione disulfide + a hydroxy-fatty-acyl-[lipid] + H2O.By similarity

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Active sitei731

GO - Molecular functioni

GO - Biological processi

  • chromatin organization Source: MGI
  • multicellular organism development Source: UniProtKB-KW
  • response to oxidative stress Source: InterPro
  • spermatogenesis Source: MGI
Complete GO annotation...

Keywords - Molecular functioni

Developmental protein, Oxidoreductase, Peroxidase

Enzyme and pathway databases

BRENDAi1.11.1.12. 3474.
ReactomeiR-MMU-2142712. Synthesis of 12-eicosatetraenoic acid derivatives.
R-MMU-2142770. Synthesis of 15-eicosatetraenoic acid derivatives.

Protein family/group databases

PeroxiBasei3714. MmGPx04-A.
3867. MmGPx04-C.

Names & Taxonomyi

Protein namesi
Recommended name:
Phospholipid hydroperoxide glutathione peroxidase, mitochondrial (EC:1.11.1.12)
Short name:
PHGPx
Alternative name(s):
Glutathione peroxidase 4
Short name:
GPx-4
Short name:
GSHPx-4
Gene namesi
Name:Gpx4
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 10

Organism-specific databases

MGIiMGI:104767. Gpx4.

Subcellular locationi

GO - Cellular componenti

  • cytosol Source: MGI
  • extracellular exosome Source: MGI
  • mitochondrial inner membrane Source: MGI
  • mitochondrion Source: MGI
  • nuclear envelope Source: MGI
  • nucleus Source: MGI
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Mitochondrion

Pathology & Biotechi

Disruption phenotypei

Embryonic lethality. The embryos die after about 7.5 days of development. Causes neurodegeneration (PubMed:18762024). Selective disruption of isoform mitochondrial causes sperm abnormalities and male infertility (PubMed:19417079). Conditional knockout in photoreceptor cells causes retinal degeneration, decreased mitochondrial biomass and decreased number of connecting cilia in these cells (PubMed:22207760).3 Publications

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_0000013069? – 197Phospholipid hydroperoxide glutathione peroxidase, mitochondrial
Transit peptidei1 – ?MitochondrionSequence analysis

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei40PhosphoserineBy similarity1

Keywords - PTMi

Phosphoprotein

Proteomic databases

PeptideAtlasiO70325.
PRIDEiO70325.

PTM databases

iPTMnetiO70325.
SwissPalmiO70325.

Expressioni

Tissue specificityi

Expressed primarily in testis and sperm midpiece (at protein level) (PubMed:19417079, PubMed:12566075). Expressed in brain (at protein level) (PubMed:22207760, PubMed:12566075). Expressed in heart, liver and kidney (at protein level) (PubMed:12566075). Expressed in retina, especially in inner segments of photoreceptor cells (at protein level) (PubMed:22207760). Widely expressed with the highest levels in testis, heart, cerebrum, ileum, stomach, liver, jejunum and epididymis (PubMed:17503194).4 Publications

Gene expression databases

BgeeiENSMUSG00000075706.
CleanExiMM_GPX4.
ExpressionAtlasiO70325. baseline and differential.
GenevisibleiO70325. MM.

Interactioni

Subunit structurei

Monomer.By similarity

Protein-protein interaction databases

BioGridi551619. 1 interactor.
IntActiO70325. 1 interactor.

Structurei

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
5L71X-ray1.80A29-197[»]
ProteinModelPortaliO70325.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Sequence similaritiesi

Belongs to the glutathione peroxidase family.Curated

Keywords - Domaini

Transit peptide

Phylogenomic databases

GeneTreeiENSGT00760000119230.
HOGENOMiHOG000277054.
HOVERGENiHBG004333.
KOiK05361.
OMAiMSLGRLC.

Family and domain databases

CDDicd00340. GSH_Peroxidase. 1 hit.
Gene3Di3.40.30.10. 1 hit.
InterProiIPR000889. Glutathione_peroxidase.
IPR029759. GPX_AS.
IPR029760. GPX_CS.
IPR012336. Thioredoxin-like_fold.
[Graphical view]
PANTHERiPTHR11592. PTHR11592. 1 hit.
PfamiPF00255. GSHPx. 1 hit.
[Graphical view]
PIRSFiPIRSF000303. Glutathion_perox. 1 hit.
PRINTSiPR01011. GLUTPROXDASE.
SUPFAMiSSF52833. SSF52833. 1 hit.
PROSITEiPS00460. GLUTATHIONE_PEROXID_1. 1 hit.
PS00763. GLUTATHIONE_PEROXID_2. 1 hit.
PS51355. GLUTATHIONE_PEROXID_3. 1 hit.
[Graphical view]

Sequences (3)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 3 isoformsi produced by alternative splicing and alternative initiation. AlignAdd to basket

Isoform Mitochondrial (identifier: O70325-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MSWGRLSRLL KPALLCGALA APGLAGTMCA SRDDWRCARS MHEFSAKDID
60 70 80 90 100
GHMVCLDKYR GFVCIVTNVA SQUGKTDVNY TQLVDLHARY AECGLRILAF
110 120 130 140 150
PCNQFGRQEP GSNQEIKEFA AGYNVKFDMY SKICVNGDDA HPLWKWMKVQ
160 170 180 190
PKGRGMLGNA IKWNFTKFLI DKNGCVVKRY GPMEEPQVIE KDLPCYL
Length:197
Mass (Da):22,229
Last modified:February 26, 2008 - v4
Checksum:i5CED4991A484F31C
GO
Isoform Nuclear (identifier: Q91XR9-1) [UniParc]FASTAAdd to basket
The sequence of this isoform can be found in the external entry Q91XR9.
Isoforms of the same protein are often annotated in two different entries if their sequences differ significantly.
Length:253
Mass (Da):29,252
GO
Isoform Cytoplasmic (identifier: O70325-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-27: Missing.

Note: Produced by alternative initiation at Met-28 of isoform Mitochondrial.
Show »
Length:170
Mass (Da):19,522
Checksum:i89AD1F6B28946C95
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti39R → A in BAA22780 (PubMed:9370288).Curated1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0187431 – 27Missing in isoform Cytoplasmic. CuratedAdd BLAST27

Non-standard residue

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Non-standard residuei73Selenocysteine1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
D87896 mRNA. Translation: BAA22780.1.
AJ012104 Genomic DNA. Translation: CAB42657.2.
AF045768 mRNA. Translation: AAC15832.1.
AF045769 mRNA. Translation: AAC15833.1.
AF044056 Genomic DNA. Translation: AAC14560.1.
AB030643 Genomic DNA. Translation: BAC06507.1.
AB030643 Genomic DNA. Translation: BAC06508.1.
AB030728 Genomic DNA. Translation: BAC06511.1.
AK006441 mRNA. Translation: BAC55251.1.
CCDSiCCDS35973.1. [O70325-1]
RefSeqiNP_001032830.2. NM_001037741.3.
NP_032188.3. NM_008162.3. [O70325-1]
UniGeneiMm.332810.
Mm.359573.

Genome annotation databases

EnsembliENSMUST00000105372; ENSMUSP00000101011; ENSMUSG00000075706. [O70325-1]
GeneIDi625249.
KEGGimmu:625249.
UCSCiuc007gbk.2. mouse. [O70325-1]

Keywords - Coding sequence diversityi

Alternative initiation, Alternative splicing, Selenocysteine

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
D87896 mRNA. Translation: BAA22780.1.
AJ012104 Genomic DNA. Translation: CAB42657.2.
AF045768 mRNA. Translation: AAC15832.1.
AF045769 mRNA. Translation: AAC15833.1.
AF044056 Genomic DNA. Translation: AAC14560.1.
AB030643 Genomic DNA. Translation: BAC06507.1.
AB030643 Genomic DNA. Translation: BAC06508.1.
AB030728 Genomic DNA. Translation: BAC06511.1.
AK006441 mRNA. Translation: BAC55251.1.
CCDSiCCDS35973.1. [O70325-1]
RefSeqiNP_001032830.2. NM_001037741.3.
NP_032188.3. NM_008162.3. [O70325-1]
UniGeneiMm.332810.
Mm.359573.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
5L71X-ray1.80A29-197[»]
ProteinModelPortaliO70325.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi551619. 1 interactor.
IntActiO70325. 1 interactor.

Protein family/group databases

PeroxiBasei3714. MmGPx04-A.
3867. MmGPx04-C.

PTM databases

iPTMnetiO70325.
SwissPalmiO70325.

Proteomic databases

PeptideAtlasiO70325.
PRIDEiO70325.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000105372; ENSMUSP00000101011; ENSMUSG00000075706. [O70325-1]
GeneIDi625249.
KEGGimmu:625249.
UCSCiuc007gbk.2. mouse. [O70325-1]

Organism-specific databases

CTDi2879.
MGIiMGI:104767. Gpx4.

Phylogenomic databases

GeneTreeiENSGT00760000119230.
HOGENOMiHOG000277054.
HOVERGENiHBG004333.
KOiK05361.
OMAiMSLGRLC.

Enzyme and pathway databases

BRENDAi1.11.1.12. 3474.
ReactomeiR-MMU-2142712. Synthesis of 12-eicosatetraenoic acid derivatives.
R-MMU-2142770. Synthesis of 15-eicosatetraenoic acid derivatives.

Miscellaneous databases

ChiTaRSiGpx4. mouse.
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000075706.
CleanExiMM_GPX4.
ExpressionAtlasiO70325. baseline and differential.
GenevisibleiO70325. MM.

Family and domain databases

CDDicd00340. GSH_Peroxidase. 1 hit.
Gene3Di3.40.30.10. 1 hit.
InterProiIPR000889. Glutathione_peroxidase.
IPR029759. GPX_AS.
IPR029760. GPX_CS.
IPR012336. Thioredoxin-like_fold.
[Graphical view]
PANTHERiPTHR11592. PTHR11592. 1 hit.
PfamiPF00255. GSHPx. 1 hit.
[Graphical view]
PIRSFiPIRSF000303. Glutathion_perox. 1 hit.
PRINTSiPR01011. GLUTPROXDASE.
SUPFAMiSSF52833. SSF52833. 1 hit.
PROSITEiPS00460. GLUTATHIONE_PEROXID_1. 1 hit.
PS00763. GLUTATHIONE_PEROXID_2. 1 hit.
PS51355. GLUTATHIONE_PEROXID_3. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiGPX41_MOUSE
AccessioniPrimary (citable) accession number: O70325
Secondary accession number(s): O35560, Q9JK35
Entry historyi
Integrated into UniProtKB/Swiss-Prot: January 11, 2001
Last sequence update: February 26, 2008
Last modified: November 30, 2016
This is version 160 of the entry and version 4 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  3. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.