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P36969

- GPX4_HUMAN

UniProt

P36969 - GPX4_HUMAN

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Protein
Phospholipid hydroperoxide glutathione peroxidase, mitochondrial
Gene
GPX4
Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5 - Experimental evidence at protein leveli

Functioni

Protects cells against membrane lipid peroxidation and cell death. Required for normal sperm development and male fertility. Could play a major role in protecting mammals from the toxicity of ingested lipid hydroperoxides. Essential for embryonic development. Protects from radiation and oxidative damage By similarity.

Catalytic activityi

2 glutathione + a lipid hydroperoxide = glutathione disulfide + lipid + 2 H2O.

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Active sitei73 – 731

GO - Molecular functioni

  1. glutathione binding Source: Ensembl
  2. glutathione peroxidase activity Source: UniProtKB
  3. phospholipid-hydroperoxide glutathione peroxidase activity Source: UniProtKB-EC
  4. selenium binding Source: Ensembl

GO - Biological processi

  1. aging Source: Ensembl
  2. arachidonic acid metabolic process Source: Reactome
  3. chromatin organization Source: Ensembl
  4. glutathione metabolic process Source: Ensembl
  5. hydrogen peroxide catabolic process Source: Ensembl
  6. lipoxygenase pathway Source: Reactome
  7. multicellular organismal development Source: UniProtKB-KW
  8. oxidation-reduction process Source: UniProtKB
  9. phospholipid metabolic process Source: UniProtKB
  10. regulation of inflammatory response Source: Ensembl
  11. response to estradiol Source: Ensembl
  12. small molecule metabolic process Source: Reactome
  13. spermatogenesis Source: Ensembl
Complete GO annotation...

Keywords - Molecular functioni

Developmental protein, Oxidoreductase, Peroxidase

Enzyme and pathway databases

BioCyciMetaCyc:HS09562-MONOMER.
ReactomeiREACT_150201. Synthesis of 12-eicosatetraenoic acid derivatives.
REACT_150209. Synthesis of 5-eicosatetraenoic acids.
REACT_150422. Synthesis of 15-eicosatetraenoic acid derivatives.
SABIO-RKP36969.

Protein family/group databases

PeroxiBasei3603. HsGPx04-A.
3632. HsGPx04-B.
3633. HsGPx04-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
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640: Chromosome 19

Organism-specific databases

HGNCiHGNC:4556. GPX4.

Subcellular locationi

GO - Cellular componenti

  1. cytosol Source: Reactome
  2. extracellular vesicular exosome Source: UniProt
  3. mitochondrial inner membrane Source: Ensembl
  4. mitochondrion Source: UniProtKB
  5. nuclear envelope Source: Ensembl
  6. nucleus Source: UniProt
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Mitochondrion

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi73 – 731U → A: Loss of enzyme activity. 1 Publication
Mutagenesisi73 – 731U → C: Almost complete loss of enzyme activity. 1 Publication

Organism-specific databases

PharmGKBiPA28952.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini? – 197Phospholipid hydroperoxide glutathione peroxidase, mitochondrialPRO_0000013067
Transit peptidei1 – ?Mitochondrion Reviewed prediction

Proteomic databases

MaxQBiP36969.
PaxDbiP36969.
PRIDEiP36969.

2D gel databases

REPRODUCTION-2DPAGEIPI00304814.
UCD-2DPAGEP36969.

PTM databases

PhosphoSiteiP36969.

Expressioni

Tissue specificityi

Present primarily in testis.

Gene expression databases

ArrayExpressiP36969.
BgeeiP36969.
CleanExiHS_GPX4.
GenevestigatoriP36969.

Organism-specific databases

HPAiCAB008630.

Interactioni

Subunit structurei

Monomer. Has a tendency to form higher mass oligomers.1 Publication

Protein-protein interaction databases

BioGridi109137. 4 interactions.
IntActiP36969. 3 interactions.
STRINGi9606.ENSP00000346103.

Structurei

Secondary structure

Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Helixi35 – 373
Helixi41 – 433
Beta strandi45 – 484
Beta strandi53 – 553
Helixi56 – 594
Beta strandi62 – 698
Beta strandi71 – 733
Helixi76 – 9015
Helixi91 – 933
Beta strandi95 – 1017
Turni104 – 1074
Helixi113 – 1219
Turni122 – 1243
Beta strandi127 – 1304
Beta strandi134 – 1374
Helixi142 – 1487
Turni151 – 1533
Beta strandi156 – 1605
Beta strandi167 – 1704
Beta strandi176 – 1805
Helixi187 – 1904
Helixi194 – 1963

3D structure databases

Select the link destinations:
PDBe
RCSB PDB
PDBj
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
2GS3X-ray1.90A36-197[»]
2OBIX-ray1.55A29-197[»]
ProteinModelPortaliP36969.
SMRiP36969. Positions 33-197.

Miscellaneous databases

EvolutionaryTraceiP36969.

Family & Domainsi

Sequence similaritiesi

Keywords - Domaini

Transit peptide

Phylogenomic databases

eggNOGiCOG0386.
HOGENOMiHOG000277054.
HOVERGENiHBG004333.
InParanoidiP36969.
KOiK05361.
OrthoDBiEOG7B5WZH.
PhylomeDBiP36969.
TreeFamiTF338735.

Family and domain databases

Gene3Di3.40.30.10. 1 hit.
InterProiIPR000889. Glutathione_peroxidase.
IPR012336. Thioredoxin-like_fold.
[Graphical view]
PANTHERiPTHR11592. PTHR11592. 1 hit.
PfamiPF00255. GSHPx. 1 hit.
[Graphical view]
PIRSFiPIRSF000303. Glutathion_perox. 1 hit.
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 (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. Align

Isoform Mitochondrial (identifier: P36969-1) [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

MSLGRLCRLL KPALLCGALA APGLAGTMCA SRDDWRCARS MHEFSAKDID    50
GHMVNLDKYR GFVCIVTNVA SQUGKTEVNY TQLVDLHARY AECGLRILAF 100
PCNQFGKQEP GSNEEIKEFA AGYNVKFDMF SKICVNGDDA HPLWKWMKIQ 150
PKGKGILGNA IKWNFTKFLI DKNGCVVKRY GPMEEPLVIE KDLPHYF 197
Length:197
Mass (Da):22,175
Last modified:February 26, 2008 - v3
Checksum:i1AE3BC7AE42FDDB1
GO
Isoform Cytoplasmic (identifier: P36969-2) [UniParc]FASTAAdd to Basket

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

Show »
Length:170
Mass (Da):19,525
Checksum:iB7FA0B3831DEF7DB
GO

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti2 – 21S → N.2 Publications
Corresponds to variant rs8178967 [ dbSNP | Ensembl ].
VAR_017063
Natural varianti120 – 1201A → T in a patient affected by cryptorchidism. 1 Publication
Corresponds to variant rs76201145 [ dbSNP | Ensembl ].
VAR_017064

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei1 – 2727Missing in isoform Cytoplasmic.
VSP_018740Add
BLAST

Non-standard residue

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Non-standard residuei73 – 731Selenocysteine

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
X71973 mRNA. Translation: CAA50793.1.
AF060972 Genomic DNA. Translation: AAC32261.1.
AY324108 Genomic DNA. Translation: AAP72965.1.
AC004151 Genomic DNA. Translation: AAC03239.1.
AC005390 Genomic DNA. Translation: AAC28920.1.
BC011836 mRNA. Translation: AAH11836.1.
BC021567 mRNA. Translation: AAH21567.1.
BC022071 mRNA. Translation: AAH22071.1.
BC032695 mRNA. Translation: AAH32695.3.
BC039849 mRNA. Translation: AAH39849.1.
CCDSiCCDS42457.1. [P36969-1]
PIRiT02747.
RefSeqiNP_001034936.1. NM_001039847.2.
NP_002076.2. NM_002085.4. [P36969-1]
UniGeneiHs.433951.

Genome annotation databases

EnsembliENST00000354171; ENSP00000346103; ENSG00000167468. [P36969-1]
GeneIDi2879.
KEGGihsa:2879.
UCSCiuc021umf.1. human. [P36969-1]

Polymorphism databases

DMDMi172045844.

Keywords - Coding sequence diversityi

Alternative initiation, Polymorphism, Selenocysteine

Cross-referencesi

Web resourcesi

NIEHS-SNPs

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
X71973 mRNA. Translation: CAA50793.1 .
AF060972 Genomic DNA. Translation: AAC32261.1 .
AY324108 Genomic DNA. Translation: AAP72965.1 .
AC004151 Genomic DNA. Translation: AAC03239.1 .
AC005390 Genomic DNA. Translation: AAC28920.1 .
BC011836 mRNA. Translation: AAH11836.1 .
BC021567 mRNA. Translation: AAH21567.1 .
BC022071 mRNA. Translation: AAH22071.1 .
BC032695 mRNA. Translation: AAH32695.3 .
BC039849 mRNA. Translation: AAH39849.1 .
CCDSi CCDS42457.1. [P36969-1 ]
PIRi T02747.
RefSeqi NP_001034936.1. NM_001039847.2.
NP_002076.2. NM_002085.4. [P36969-1 ]
UniGenei Hs.433951.

3D structure databases

Select the link destinations:
PDBe
RCSB PDB
PDBj
Links Updated
Entry Method Resolution (Å) Chain Positions PDBsum
2GS3 X-ray 1.90 A 36-197 [» ]
2OBI X-ray 1.55 A 29-197 [» ]
ProteinModelPortali P36969.
SMRi P36969. Positions 33-197.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

BioGridi 109137. 4 interactions.
IntActi P36969. 3 interactions.
STRINGi 9606.ENSP00000346103.

Chemistry

DrugBanki DB00143. Glutathione.

Protein family/group databases

PeroxiBasei 3603. HsGPx04-A.
3632. HsGPx04-B.
3633. HsGPx04-C.

PTM databases

PhosphoSitei P36969.

Polymorphism databases

DMDMi 172045844.

2D gel databases

REPRODUCTION-2DPAGE IPI00304814.
UCD-2DPAGE P36969.

Proteomic databases

MaxQBi P36969.
PaxDbi P36969.
PRIDEi P36969.

Protocols and materials databases

DNASUi 2879.
Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENST00000354171 ; ENSP00000346103 ; ENSG00000167468 . [P36969-1 ]
GeneIDi 2879.
KEGGi hsa:2879.
UCSCi uc021umf.1. human. [P36969-1 ]

Organism-specific databases

CTDi 2879.
GeneCardsi GC19P001103.
HGNCi HGNC:4556. GPX4.
HPAi CAB008630.
MIMi 138322. gene.
neXtProti NX_P36969.
PharmGKBi PA28952.
GenAtlasi Search...

Phylogenomic databases

eggNOGi COG0386.
HOGENOMi HOG000277054.
HOVERGENi HBG004333.
InParanoidi P36969.
KOi K05361.
OrthoDBi EOG7B5WZH.
PhylomeDBi P36969.
TreeFami TF338735.

Enzyme and pathway databases

BioCyci MetaCyc:HS09562-MONOMER.
Reactomei REACT_150201. Synthesis of 12-eicosatetraenoic acid derivatives.
REACT_150209. Synthesis of 5-eicosatetraenoic acids.
REACT_150422. Synthesis of 15-eicosatetraenoic acid derivatives.
SABIO-RK P36969.

Miscellaneous databases

ChiTaRSi GPX4. human.
EvolutionaryTracei P36969.
GeneWikii GPX4.
GenomeRNAii 2879.
NextBioi 11367.
PROi P36969.
SOURCEi Search...

Gene expression databases

ArrayExpressi P36969.
Bgeei P36969.
CleanExi HS_GPX4.
Genevestigatori P36969.

Family and domain databases

Gene3Di 3.40.30.10. 1 hit.
InterProi IPR000889. Glutathione_peroxidase.
IPR012336. Thioredoxin-like_fold.
[Graphical view ]
PANTHERi PTHR11592. PTHR11592. 1 hit.
Pfami PF00255. GSHPx. 1 hit.
[Graphical view ]
PIRSFi PIRSF000303. Glutathion_perox. 1 hit.
SUPFAMi SSF52833. SSF52833. 1 hit.
PROSITEi PS00460. GLUTATHIONE_PEROXID_1. 1 hit.
PS00763. GLUTATHIONE_PEROXID_2. 1 hit.
PS51355. GLUTATHIONE_PEROXID_3. 1 hit.
[Graphical view ]
ProtoNeti Search...

Publicationsi

« Hide 'large scale' publications
  1. "Cloning and sequencing of the cDNA encoding a human testis phospholipid hydroperoxide glutathione peroxidase."
    Esworthy R.S., Doan K., Doroshow J.H., Chu F.-F.
    Gene 144:317-318(1994) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].
    Tissue: Testis.
  2. "Structural organization of the human selenium-dependent phospholipid hydroperoxide glutathione peroxidase gene (GPX4): chromosomal localization to 19p13.3."
    Kelner M.J., Montoya M.A.
    Biochem. Biophys. Res. Commun. 249:53-55(1998) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
  3. NIEHS SNPs program
    Submitted (JUN-2003) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANT ASN-2.
  4. "The DNA sequence and biology of human chromosome 19."
    Grimwood J., Gordon L.A., Olsen A.S., Terry A., Schmutz J., Lamerdin J.E., Hellsten U., Goodstein D., Couronne O., Tran-Gyamfi M., Aerts A., Altherr M., Ashworth L., Bajorek E., Black S., Branscomb E., Caenepeel S., Carrano A.V.
    , Caoile C., Chan Y.M., Christensen M., Cleland C.A., Copeland A., Dalin E., Dehal P., Denys M., Detter J.C., Escobar J., Flowers D., Fotopulos D., Garcia C., Georgescu A.M., Glavina T., Gomez M., Gonzales E., Groza M., Hammon N., Hawkins T., Haydu L., Ho I., Huang W., Israni S., Jett J., Kadner K., Kimball H., Kobayashi A., Larionov V., Leem S.-H., Lopez F., Lou Y., Lowry S., Malfatti S., Martinez D., McCready P.M., Medina C., Morgan J., Nelson K., Nolan M., Ovcharenko I., Pitluck S., Pollard M., Popkie A.P., Predki P., Quan G., Ramirez L., Rash S., Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A., She X., Smith D., Slezak T., Solovyev V., Thayer N., Tice H., Tsai M., Ustaszewska A., Vo N., Wagner M., Wheeler J., Wu K., Xie G., Yang J., Dubchak I., Furey T.S., DeJong P., Dickson M., Gordon D., Eichler E.E., Pennacchio L.A., Richardson P., Stubbs L., Rokhsar D.S., Myers R.M., Rubin E.M., Lucas S.M.
    Nature 428:529-535(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  5. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
    The MGC Project Team
    Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
    Tissue: Brain, Eye, Lung, Pancreas and Testis.
  6. Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
  7. "Structural basis for catalytic activity and enzyme polymerization of phospholipid hydroperoxide glutathione peroxidase-4 (GPx4)."
    Scheerer P., Borchert A., Krauss N., Wessner H., Gerth C., Hoehne W., Kuhn H.
    Biochemistry 46:9041-9049(2007) [PubMed] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (1.55 ANGSTROMS) OF 29-197 (ISOFORM CYTOPLASMIC), SUBUNIT, MUTAGENESIS OF SEC-73.
  8. "Crystal structure of the selenocysteine to glycine mutant of human glutathione peroxidase 4 (GPX4)."
    Structural genomics consortium (SGC)
    Submitted (FEB-2009) to the PDB data bank
    Cited for: X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS) OF 36-197.
  9. Cited for: VARIANTS ASN-2 AND THR-120.

Entry informationi

Entry nameiGPX4_HUMAN
AccessioniPrimary (citable) accession number: P36969
Secondary accession number(s): O43381, Q6PJ59, Q9UPK2
Entry historyi
Integrated into UniProtKB/Swiss-Prot: June 1, 1994
Last sequence update: February 26, 2008
Last modified: September 3, 2014
This is version 154 of the entry and version 3 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 19
    Human chromosome 19: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

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