GPX4

Protein identityUniProt · HPA

UniProt accession

P36969

Gene

GPX4

Ensembl

ENSG00000167468

Chromosome

19

Canonical length

197 aa

Protein class

Disease related genes, Enzymes, Human disease related genes, Metabolic proteins, Plasma proteins, Potential drug targets, Predicted intracellular proteins

Subcellular location

Nucleoplasm,Mitochondria

Secretome location

Intracellular and membrane

OverviewNCBI Gene

The protein encoded by this gene belongs to the glutathione peroxidase family, members of which catalyze the reduction of hydrogen peroxide, organic hydroperoxides and lipid hydroperoxides, and thereby protect cells against oxidative damage. Several isozymes of this gene family exist in vertebrates, which vary in cellular location and substrate specificity. This isozyme has a high preference for lipid hydroperoxides and protects cells against membrane lipid peroxidation and cell death. It is also required for normal sperm development; thus, it has been identified as a 'moonlighting' protein because of its ability to serve dual functions as a peroxidase, as well as a structural protein in mature spermatozoa. Mutations in this gene are associated with Sedaghatian type of spondylometaphyseal dysplasia (SMDS). This isozyme is also a selenoprotein, containing the rare amino acid selenocysteine (Sec) at its active site. Sec is encoded by the UGA codon, which normally signals translation termination. The 3' UTRs of selenoprotein mRNAs contain a conserved stem-loop structure, designated the Sec insertion sequence (SECIS) element, that is necessary for the recognition of UGA as a Sec codon, rather than as a stop signal. Transcript variants resulting from alternative splicing or use of alternate promoters have been described to encode isoforms with different subcellular localization. [provided by RefSeq, Dec 2018]

Canonical amino-acid sequenceUniProt

197 residues, UniProt reviewed canonical sequence.

>P36969|GPX4
     1  MSLGRLCRLL KPALLCGALA APGLAGTMCA SRDDWRCARS MHEFSAKDID GHMVNLDKYR
    61  GFVCIVTNVA SQUGKTEVNY TQLVDLHARY AECGLRILAF PCNQFGKQEP GSNEEIKEFA
   121  AGYNVKFDMF SKICVNGDDA HPLWKWMKIQ PKGKGILGNA IKWNFTKFLI DKNGCVVKRY
   181  GPMEEPLVIE KDLPHYF

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against GPX4 can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability

Intracellular

Secreted

No

Transmembrane segments

0

Mean surface accessibility (rSASA)

0

Highest tissue expression

1,353 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about GPX4.

Disease | AllUniProt

Conditions GPX4 is implicated in, by any mechanism.

• Spondylometaphyseal dysplasia, Sedaghatian type (SMDS) MIM:250220

Disease | GeneticClinVar

16 pathogenic / likely-pathogenic of 234 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Spondylometaphyseal dysplasia, Sedaghatian type
• GPX4-related disorder

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance)

1.28

gnomAD pLI

0

gnomAD missense Z

-1.08

DepMap mean gene effect

-0.83

DepMap dependency class

common

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 5% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• apoptotic process
• arachidonate metabolic process
• cerebellum development
• chromatin organization
• dendrite development
• lipoxygenase pathway
• long-chain fatty acid biosynthetic process
• multicellular organism growth
• negative regulation of ferroptosis
• phospholipid metabolic process
• protein polymerization
• response to estradiol
• response to lipopolysaccharide
• response to oxidative stress
• spermatogenesis

Molecular functions

• glutathione peroxidase activity
• identical protein binding
• phospholipid-hydroperoxide glutathione peroxidase activity
• selenium binding

Cellular components

• cytosol
• extracellular exosome
• mitochondrion
• nuclear envelope
• nucleus
• protein-containing complex

Protein domainsUniProt · Pfam · InterPro

• Glutathione peroxidase
• Glutathione peroxidase active site
• Glutathione peroxidase conserved site
• Thioredoxin-like superfamily
• Glutathione peroxidase

KeywordsUniProt

• Alternative initiation
• Cytoplasm
• Developmental protein
• Dwarfism
• Hydroxylation
• Lipid metabolism
• Mitochondrion
• Oxidoreductase
• Peroxidase
• Phosphoprotein
• Selenocysteine
• Transit peptide

InteractionsUniProt · HPA

Protein binding partners of GPX4 in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• FUNDC1