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Protein

Phospholipid hydroperoxide glutathione peroxidase

Gene

GPX4

Organism
Sus scrofa (Pig)
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 (PubMed:3978121, PubMed:2386798, PubMed:8135530). Can also reduce fatty acid hydroperoxide, cholesterol hydroperoxide and thymine hydroperoxide (PubMed:8135530). Plays a key role in protecting cells from oxidative damage by preventing membrane lipid peroxidation (By similarity). 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 similarity3 Publications

Catalytic activityi

2 glutathione + a hydroperoxy-fatty-acyl-[lipid] = glutathione disulfide + a hydroxy-fatty-acyl-[lipid] + H2O.3 Publications

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Active sitei731 Publication1

GO - Molecular functioni

GO - Biological processi

Keywordsi

Molecular functionDevelopmental protein, Oxidoreductase, Peroxidase

Protein family/group databases

PeroxiBasei3723 SscGPx04

Chemistry databases

SwissLipidsiSLP:000001475

Names & Taxonomyi

Protein namesi
Recommended name:
Phospholipid hydroperoxide glutathione peroxidase2 Publications (EC:1.11.1.123 Publications)
Short name:
PHGPx2 Publications
Alternative name(s):
Glutathione peroxidase 4By similarity
Short name:
GPx-4By similarity
Short name:
GSHPx-4By similarity
Gene namesi
Name:GPX4By similarity
OrganismiSus scrofa (Pig)
Taxonomic identifieri9823 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaLaurasiatheriaCetartiodactylaSuinaSuidaeSus
Proteomesi
  • UP000008227 Componenti: Chromosome 2

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

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_0000013071? – 197Phospholipid hydroperoxide glutathione peroxidase
Transit peptidei1 – ?MitochondrionSequence analysis

Proteomic databases

PaxDbiP36968
PeptideAtlasiP36968
PRIDEiP36968

Expressioni

Gene expression databases

GenevisibleiP36968 SS

Interactioni

Subunit structurei

Monomer (PubMed:3978121). Has a tendency to form higher mass oligomers (By similarity).By similarity1 Publication

GO - Molecular functioni

Protein-protein interaction databases

STRINGi9823.ENSSSCP00000021702

Structurei

3D structure databases

ProteinModelPortaliP36968
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Sequence similaritiesi

Belongs to the glutathione peroxidase family.Curated

Keywords - Domaini

Transit peptide

Phylogenomic databases

eggNOGiENOG410JKJH Eukaryota
ENOG410ZC0K LUCA
GeneTreeiENSGT00760000119230
HOVERGENiHBG004333
InParanoidiP36968
KOiK05361
OrthoDBiEOG091G0OJG

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 (2)i

Sequence statusi: Complete.

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

This entry describes 2 isoformsi produced by alternative initiation. AlignAdd to basket

Isoform Mitochondrial (identifier: P36968-1) [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
MSFSRLFRLL KPTLLCGTLA VPGLAGTMCA SRDDWRCARS MHEFSAKDID
60 70 80 90 100
GHMVNLDKYR GYVCIVTNVA SQUGKTEVNY TQLVDLHARY AECGLRILAF
110 120 130 140 150
PCNQFGRQEP GSDAEIKEFA AGYNVKFDMF SKICVNGDDA HPLWKWMKVQ
160 170 180 190
PKGRGMLGNA IKWNFTKFLI DKNGCVVKRY GPMEEPQVIE KDLPCYL
Length:197
Mass (Da):22,337
Last modified:February 26, 2008 - v3
Checksum:i34865B0BEBFA69D0
GO
Isoform Cytoplasmic (identifier: P36968-2) [UniParc]FASTAAdd to basket

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

Show »
Length:170
Mass (Da):19,491
Checksum:iEBA2276405A6FACE
GO

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0187441 – 27Missing in isoform Cytoplasmic. 2 PublicationsAdd BLAST27

Non-standard residue

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

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
L12743 mRNA Translation: AAA31098.2
L12743 mRNA Translation: AAA31099.2
X76008 Genomic DNA Translation: CAA53595.2
X76009 mRNA Translation: CAA53596.2
S80257 mRNA Translation: AAB21327.2
PIRiJN0608
RefSeqiNP_999572.1, NM_214407.1 [P36968-1]
UniGeneiSsc.93915

Genome annotation databases

EnsembliENSSSCT00000051893; ENSSSCP00000046912; ENSSSCG00000024052 [P36968-1]
GeneIDi399537
KEGGissc:399537

Keywords - Coding sequence diversityi

Alternative initiation, Selenocysteine

Similar proteinsi

Entry informationi

Entry nameiGPX4_PIG
AccessioniPrimary (citable) accession number: P36968
Entry historyiIntegrated into UniProtKB/Swiss-Prot: June 1, 1994
Last sequence update: February 26, 2008
Last modified: April 25, 2018
This is version 124 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, Direct protein sequencing, Reference proteome
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Main funding by: National Institutes of Health