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Protein

Phospholipid hydroperoxide glutathione peroxidase

Gene

Gpx4

Organism
Rattus norvegicus (Rat)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

Essential antioxidant peroxidase that directly reduces phospholipid hydroperoxide even if they are incorporated in membranes and lipoproteins (By similarity). Can also reduce fatty acid hydroperoxide, cholesterol hydroperoxide and thymine hydroperoxide (By similarity). Plays a key role in protecting cells from oxidative damage by preventing membrane lipid peroxidation (PubMed:1556123, PubMed:9988735). Required to prevent cells from ferroptosis, a non-apoptotic cell death resulting from an iron-dependent accumulation of lipid reactive oxygen species (By similarity). The presence of selenocysteine (Sec) versus Cys at the active site is essential for life: it provides resistance to overoxidation and prevents cells against ferroptosis (By similarity). The presence of Sec at the active site is also essential for the survival of a specific type of parvalbumin-positive interneurons, thereby preventing against fatal epileptic seizures (By similarity). May be required to protect cells from the toxicity of ingested lipid hydroperoxides (By similarity). Required for normal sperm development and male fertility (By similarity). Essential for maturation and survival of photoreceptor cells (By similarity). Plays a role in a primary T-cell response to viral and parasitic infection by protecting T-cells from ferroptosis and by supporting T-cell expansion (By similarity).By similarity2 Publications
Isoform Cytoplasmic: Specifically able to suppress the production of leukotriene and prostaglandin in response to several stimuli by reducing fatty acid hydroperoxide (PubMed:9442035, PubMed:11010961).2 Publications
Isoform Mitochondrial: Specifically required to prevent mitochondrial cell death by mediating reduction of cardiolipin hydroperoxide (PubMed:9988735, PubMed:10506188, PubMed:10998361). Also required for normal sperm development and male fertility (By similarity).By similarity3 Publications
Isoform Nuclear: Required for male fertility by stabilizing the condensed chromatin in sperm nuclei.By similarity

Catalytic activityi

2 glutathione + a hydroperoxy-fatty-acyl-[lipid] = glutathione disulfide + a hydroxy-fatty-acyl-[lipid] + H2O.1 Publication

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Active sitei73By similarity1

GO - Molecular functioni

  • glutathione peroxidase activity Source: RGD
  • identical protein binding Source: RGD
  • phospholipid-hydroperoxide glutathione peroxidase activity Source: RGD
  • selenium binding Source: RGD

GO - Biological processi

  • aging Source: RGD
  • chromatin organization Source: UniProtKB
  • glutathione metabolic process Source: RGD
  • multicellular organism development Source: UniProtKB-KW
  • negative regulation of ferroptosis Source: UniProtKB
  • protein polymerization Source: RGD
  • regulation of inflammatory response Source: RGD
  • response to estradiol Source: RGD
  • response to oxidative stress Source: InterPro
  • spermatogenesis Source: UniProtKB

Keywordsi

Molecular functionDevelopmental protein, Oxidoreductase, Peroxidase

Enzyme and pathway databases

BRENDAi1.11.1.12. 5301.

Protein family/group databases

PeroxiBasei3733. RnoGPx04-A.
3812. RnoGPx04-B.
3813. RnoGPx04-C.

Names & Taxonomyi

Protein namesi
Recommended name:
Phospholipid hydroperoxide glutathione peroxidase1 Publication (EC:1.11.1.121 Publication)
Short name:
PHGPx1 Publication
Alternative name(s):
Glutathione peroxidase 4By similarity
Short name:
GPx-4By similarity
Short name:
GSHPx-4By similarity
Gene namesi
Name:Gpx4By similarity
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeRattus
Proteomesi
  • UP000002494 Componenti: Chromosome 7

Organism-specific databases

RGDi69226. Gpx4.

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cytoplasm, Mitochondrion, Nucleus

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_0000013073? – 197Phospholipid hydroperoxide glutathione peroxidase
Transit peptidei1 – ?MitochondrionSequence analysis

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei40PhosphoserineCombined sources1

Keywords - PTMi

Phosphoprotein

Proteomic databases

PaxDbiQ91XR8.
PRIDEiP36970.

PTM databases

iPTMnetiP36970.
PhosphoSitePlusiQ91XR8.
SwissPalmiP36970.

Expressioni

Tissue specificityi

Present primarily in testis (PubMed:1556123). Expressed in flagella of epididymal sperm (PubMed:19423663). Isoform Cytoplasmic: Highly expressed in testis (PubMed:14575705). Present in spermatogonia, spermatocyte and spermatid (at protein level) (PubMed:14575705).3 Publications

Gene expression databases

GenevisibleiQ76LU9. RN.

Interactioni

Subunit structurei

Monomer. Has a tendency to form higher mass oligomers.By similarity

GO - Molecular functioni

Structurei

3D structure databases

ProteinModelPortaliP36970.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Sequence similaritiesi

Belongs to the glutathione peroxidase family.Curated

Keywords - Domaini

Transit peptide

Phylogenomic databases

eggNOGiKOG1651. Eukaryota.
COG0386. LUCA.
GeneTreeiENSGT00760000119230.
HOGENOMiHOG000277054.
HOVERGENiHBG004333.
InParanoidiQ91XR8.
KOiK05361.
PhylomeDBiP36970.

Family and domain databases

CDDicd00340. GSH_Peroxidase. 1 hit.
InterProiView protein in InterPro
IPR000889. Glutathione_peroxidase.
IPR029759. GPX_AS.
IPR029760. GPX_CS.
IPR036249. Thioredoxin-like_sf.
PANTHERiPTHR11592. PTHR11592. 1 hit.
PfamiView protein in Pfam
PF00255. GSHPx. 1 hit.
PIRSFiPIRSF000303. Glutathion_perox. 1 hit.
PRINTSiPR01011. GLUTPROXDASE.
SUPFAMiSSF52833. SSF52833. 1 hit.
PROSITEiView protein in PROSITE
PS00460. GLUTATHIONE_PEROXID_1. 1 hit.
PS00763. GLUTATHIONE_PEROXID_2. 1 hit.
PS51355. GLUTATHIONE_PEROXID_3. 1 hit.

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: P36970-1) [UniParc]FASTAAdd to basket
Also known as: L-form1 Publication

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 VPGLAGTMCA SRDDWRCARS MHEFAAKDID
60 70 80 90 100
GHMVCLDKYR GCVCIVTNVA SQUGKTDVNY TQLVDLHARY AECGLRILAF
110 120 130 140 150
PCNQFGRQEP GSNQEIKEFA AGYNVRFDMY SKICVNGDDA HPLWKWMKVQ
160 170 180 190
PKGRGMLGNA IKWNFTKFLI DKNGCVVKRY GPMEEPQVIE KDLPCYL
Length:197
Mass (Da):22,225
Last modified:February 26, 2008 - v3
Checksum:i83FF001A5A42F814
GO
Isoform Cytoplasmic (identifier: P36970-2) [UniParc]FASTAAdd to basket
Also known as: S-form1 Publication

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):19,490
Checksum:iA882EE0827902EA0
GO
Isoform Nuclear (identifier: P36970-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-28: MSWGRLSRLLKPALLCGALAVPGLAGTM → MGRAAARKRG...TSNSHEFLGL

Show »
Length:253
Mass (Da):29,335
Checksum:iD108602E22DAD29A
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti45A → S in AAC52503 (PubMed:7592947).Curated1
Sequence conflicti45A → S in CAD61276 (PubMed:12819198).Curated1
Sequence conflicti45A → S in CAD61277 (PubMed:12819198).Curated1
Sequence conflicti45A → S in CAD61278 (PubMed:12819198).Curated1
Sequence conflicti133I → V in BAC87836 (PubMed:14575705).Curated1
Sequence conflicti136N → S in AAS76675 (Ref. 4) Curated1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0593501 – 28MSWGR…LAGTM → MGRAAARKRGRCRQRGRSPG GRRRREPGRQSPRKRPGPRR RRARARRRRRARPRRMEPIP EPFNPRPLLQDLPQTSNSHE FLGL in isoform Nuclear. Add BLAST28
Alternative sequenceiVSP_0187461 – 27Missing in isoform Cytoplasmic. CuratedAdd BLAST27

Non-standard residue

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Non-standard residuei73Selenocysteine1 Publication1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U37427 mRNA. Translation: AAC52503.2.
AB072798 mRNA. Translation: BAC87836.1.
AJ537598 Genomic DNA. Translation: CAD61276.1.
AJ537598 Genomic DNA. Translation: CAD61277.1.
AJ537598 Genomic DNA. Translation: CAD61278.1.
X82679 mRNA. Translation: CAA57996.1.
AY570513 mRNA. Translation: AAS76675.1.
AF274028 mRNA. Translation: AAK74113.1.
L24896 mRNA. Translation: AAA41842.2.
PIRiJC4332.
RefSeqiNP_001034938.1. NM_001039849.2.
NP_058861.3. NM_017165.3. [P36970-1]
UniGeneiRn.3647.

Genome annotation databases

EnsembliENSRNOT00000093376; ENSRNOP00000076198; ENSRNOG00000013604. [P36970-1]
ENSRNOT00000093426; ENSRNOP00000076309; ENSRNOG00000013604. [P36970-3]
GeneIDi29328.
KEGGirno:29328.

Keywords - Coding sequence diversityi

Alternative initiation, Alternative splicing, Selenocysteine

Similar proteinsi

Entry informationi

Entry nameiGPX4_RAT
AccessioniPrimary (citable) accession number: P36970
Secondary accession number(s): Q6PZ55, Q76LU9, Q91XR8
Entry historyiIntegrated into UniProtKB/Swiss-Prot: June 1, 1994
Last sequence update: February 26, 2008
Last modified: March 28, 2018
This is version 143 of the entry and version 3 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome