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Protein

Phospholipid hydroperoxide glutathione peroxidase

Gene

GPX4

Organism
Bos taurus (Bovine)
Status
Reviewed-Annotation score: -Experimental evidence at transcript 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. Required to prevent cells from ferroptosis, a non-apoptotic cell death resulting from an iron-dependent accumulation of lipid reactive oxygen species. 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. 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. May be required to protect cells from the toxicity of ingested lipid hydroperoxides. Required for normal sperm development and male fertility. Essential for maturation and survival of photoreceptor cells. 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 similarity

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 sitei73By similarity1

GO - Molecular functioni

GO - Biological processi

Keywordsi

Molecular functionDevelopmental protein, Oxidoreductase, Peroxidase

Enzyme and pathway databases

BRENDAi1.11.1.12 908

Protein family/group databases

PeroxiBasei3637 BtGPx04-A

Names & Taxonomyi

Protein namesi
Recommended name:
Phospholipid hydroperoxide glutathione peroxidaseBy similarity (EC:1.11.1.12By similarity)
Short name:
PHGPxBy similarity
Alternative name(s):
Glutathione peroxidase 4By similarity
Short name:
GPx-4By similarity
Short name:
GSHPx-4By similarity
Gene namesi
Name:GPX4By similarity
OrganismiBos taurus (Bovine)
Taxonomic identifieri9913 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaLaurasiatheriaCetartiodactylaRuminantiaPecoraBovidaeBovinaeBos
Proteomesi
  • UP000009136 Componenti: Unplaced

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_0000013065? – 197Phospholipid hydroperoxide glutathione peroxidase
Transit peptidei1 – ?MitochondrionSequence analysis

Proteomic databases

PRIDEiQ9N2J2

Interactioni

Subunit structurei

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

Structurei

3D structure databases

ProteinModelPortaliQ9N2J2
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Sequence similaritiesi

Belongs to the glutathione peroxidase family.Curated

Keywords - Domaini

Transit peptide

Phylogenomic databases

HOVERGENiHBG004333
InParanoidiQ9N2J2
KOiK05361

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: Q9N2J2-1) [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
MSFSRLYRLL KPALLCGALA APGLASTMCA SRDDWRCARS MHEFSAKDID
60 70 80 90 100
GRMVNLDKYR GHVCIVTNVA SQUGKTDVNY TQLVDLHARY AECGLRILAF
110 120 130 140 150
PCNQFGRQEP GSNAEIKEFA AGYNVKFDLF SKICVNGDDA HPLWKWMKVQ
160 170 180 190
PKGRGMLGNA IKWNFTKFLI DKNGCVVKRY GPMEEPLVIE KDLPCYL
Length:197
Mass (Da):22,240
Last modified:February 26, 2008 - v2
Checksum:i3C05FF92C4AA8824
GO
Isoform Cytoplasmic (identifier: Q9N2J2-2) [UniParc]FASTAAdd to basket

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

Show »
Length:170
Mass (Da):19,436
Checksum:i0D89F887D30253BD
GO

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0187381 – 27Missing in isoform Cytoplasmic. CuratedAdd BLAST27

Non-standard residue

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Non-standard residuei73SelenocysteineBy similarity1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AB017534 mRNA Translation: BAA86034.1
RefSeqiNP_777195.1, NM_174770.4 [Q9N2J2-1]
UniGeneiBt.49234

Genome annotation databases

GeneIDi286809
KEGGibta:286809

Keywords - Coding sequence diversityi

Alternative initiation, Selenocysteine

Similar proteinsi

Entry informationi

Entry nameiGPX4_BOVIN
AccessioniPrimary (citable) accession number: Q9N2J2
Entry historyiIntegrated into UniProtKB/Swiss-Prot: August 16, 2004
Last sequence update: February 26, 2008
Last modified: March 28, 2018
This is version 103 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome
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Main funding by: National Institutes of Health