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Protein

Phospholipid hydroperoxide glutathione peroxidase, mitochondrial

Gene

Gpx4

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Protects cells against membrane lipid peroxidation and cell death. Isoform mitochondrial is 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.3 Publications

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 peroxidase activity Source: MGI
  2. phospholipid-hydroperoxide glutathione peroxidase activity Source: UniProtKB-EC

GO - Biological processi

  1. chromatin organization Source: MGI
  2. multicellular organismal development Source: UniProtKB-KW
  3. response to oxidative stress Source: InterPro
  4. spermatogenesis Source: MGI
Complete GO annotation...

Keywords - Molecular functioni

Developmental protein, Oxidoreductase, Peroxidase

Enzyme and pathway databases

ReactomeiREACT_196559. Synthesis of 15-eicosatetraenoic acid derivatives.
REACT_196569. Synthesis of 12-eicosatetraenoic acid derivatives.
REACT_206751. Synthesis of 5-eicosatetraenoic acids.

Protein family/group databases

PeroxiBasei3714. MmGPx04-A.
3867. MmGPx04-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
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
ProteomesiUP000000589: Chromosome 10

Organism-specific databases

MGIiMGI:104767. Gpx4.

Subcellular locationi

GO - Cellular componenti

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

Keywords - Cellular componenti

Cytoplasm, Mitochondrion

Pathology & Biotechi

Disruption phenotypei

Embryonic lethality. The embryos die after about 7.5 days of development. Causes neurodegeneration. Selective disruption of isoform mitochondrial causes sperm abnormalities and male infertility.2 Publications

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini? – 197Phospholipid hydroperoxide glutathione peroxidase, mitochondrialPRO_0000013069
Transit peptidei1 – ?MitochondrionSequence Analysis

Proteomic databases

PaxDbiO70325.
PRIDEiO70325.

Expressioni

Tissue specificityi

Detected in testis and sperm midpiece (at protein level). Present primarily in testis.1 Publication

Gene expression databases

BgeeiO70325.
CleanExiMM_GPX4.
ExpressionAtlasiO70325. baseline and differential.
GenevestigatoriO70325.

Interactioni

Subunit structurei

Monomer.By similarity

Protein-protein interaction databases

BioGridi551619. 1 interaction.
IntActiO70325. 1 interaction.

Structurei

3D structure databases

ProteinModelPortaliO70325.
SMRiO70325. Positions 33-197.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Sequence similaritiesi

Belongs to the glutathione peroxidase family.Curated

Keywords - Domaini

Transit peptide

Phylogenomic databases

eggNOGiCOG0386.
GeneTreeiENSGT00760000119230.
HOGENOMiHOG000277054.
HOVERGENiHBG004333.
KOiK05361.
OMAiTCLAPAT.
OrthoDBiEOG7B5WZH.

Family and domain databases

Gene3Di3.40.30.10. 1 hit.
InterProiIPR000889. Glutathione_peroxidase.
IPR029759. GPX_AS.
IPR029760. GPX_CS.
IPR012336. Thioredoxin-like_fold.
[Graphical view]
PANTHERiPTHR11592. PTHR11592. 1 hit.
PfamiPF00255. GSHPx. 1 hit.
[Graphical view]
PIRSFiPIRSF000303. Glutathion_perox. 1 hit.
PRINTSiPR01011. GLUTPROXDASE.
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 (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. Align

Isoform Mitochondrial (identifier: O70325-1) [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
MSWGRLSRLL KPALLCGALA APGLAGTMCA SRDDWRCARS MHEFSAKDID
60 70 80 90 100
GHMVCLDKYR GFVCIVTNVA SQUGKTDVNY TQLVDLHARY AECGLRILAF
110 120 130 140 150
PCNQFGRQEP GSNQEIKEFA AGYNVKFDMY SKICVNGDDA HPLWKWMKVQ
160 170 180 190
PKGRGMLGNA IKWNFTKFLI DKNGCVVKRY GPMEEPQVIE KDLPCYL
Length:197
Mass (Da):22,229
Last modified:February 26, 2008 - v4
Checksum:i5CED4991A484F31C
GO
Isoform Nuclear (identifier: Q91XR9-1) [UniParc]FASTAAdd to Basket

The sequence of this isoform can be found in the external entry Q91XR9.
Isoforms of the same protein are often annotated in two different entries if their sequences differ significantly.
Length:253
Mass (Da):29,252
GO
Isoform Cytoplasmic (identifier: O70325-2) [UniParc]FASTAAdd to Basket

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):19,522
Checksum:i89AD1F6B28946C95
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti39 – 391R → A in BAA22780. (PubMed:9370288)Curated

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei1 – 2727Missing in isoform Cytoplasmic. CuratedVSP_018743Add
BLAST

Non-standard residue

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

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
D87896 mRNA. Translation: BAA22780.1.
AJ012104 Genomic DNA. Translation: CAB42657.2.
AF045768 mRNA. Translation: AAC15832.1.
AF045769 mRNA. Translation: AAC15833.1.
AF044056 Genomic DNA. Translation: AAC14560.1.
AB030643 Genomic DNA. Translation: BAC06507.1.
AB030643 Genomic DNA. Translation: BAC06508.1.
AB030728 Genomic DNA. Translation: BAC06511.1.
AK006441 mRNA. Translation: BAC55251.1.
CCDSiCCDS35973.1. [O70325-1]
RefSeqiNP_001032830.2. NM_001037741.3.
NP_032188.3. NM_008162.3. [O70325-1]
UniGeneiMm.332810.
Mm.359573.

Genome annotation databases

EnsembliENSMUST00000105372; ENSMUSP00000101011; ENSMUSG00000075706. [O70325-1]
GeneIDi625249.
KEGGimmu:625249.
UCSCiuc007gbk.1. mouse. [O70325-1]

Keywords - Coding sequence diversityi

Alternative initiation, Alternative splicing, Selenocysteine

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
D87896 mRNA. Translation: BAA22780.1.
AJ012104 Genomic DNA. Translation: CAB42657.2.
AF045768 mRNA. Translation: AAC15832.1.
AF045769 mRNA. Translation: AAC15833.1.
AF044056 Genomic DNA. Translation: AAC14560.1.
AB030643 Genomic DNA. Translation: BAC06507.1.
AB030643 Genomic DNA. Translation: BAC06508.1.
AB030728 Genomic DNA. Translation: BAC06511.1.
AK006441 mRNA. Translation: BAC55251.1.
CCDSiCCDS35973.1. [O70325-1]
RefSeqiNP_001032830.2. NM_001037741.3.
NP_032188.3. NM_008162.3. [O70325-1]
UniGeneiMm.332810.
Mm.359573.

3D structure databases

ProteinModelPortaliO70325.
SMRiO70325. Positions 33-197.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi551619. 1 interaction.
IntActiO70325. 1 interaction.

Protein family/group databases

PeroxiBasei3714. MmGPx04-A.
3867. MmGPx04-C.

Proteomic databases

PaxDbiO70325.
PRIDEiO70325.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000105372; ENSMUSP00000101011; ENSMUSG00000075706. [O70325-1]
GeneIDi625249.
KEGGimmu:625249.
UCSCiuc007gbk.1. mouse. [O70325-1]

Organism-specific databases

CTDi2879.
MGIiMGI:104767. Gpx4.

Phylogenomic databases

eggNOGiCOG0386.
GeneTreeiENSGT00760000119230.
HOGENOMiHOG000277054.
HOVERGENiHBG004333.
KOiK05361.
OMAiTCLAPAT.
OrthoDBiEOG7B5WZH.

Enzyme and pathway databases

ReactomeiREACT_196559. Synthesis of 15-eicosatetraenoic acid derivatives.
REACT_196569. Synthesis of 12-eicosatetraenoic acid derivatives.
REACT_206751. Synthesis of 5-eicosatetraenoic acids.

Miscellaneous databases

ChiTaRSiGpx4. mouse.
NextBioi418158.
PROiO70325.
SOURCEiSearch...

Gene expression databases

BgeeiO70325.
CleanExiMM_GPX4.
ExpressionAtlasiO70325. baseline and differential.
GenevestigatoriO70325.

Family and domain databases

Gene3Di3.40.30.10. 1 hit.
InterProiIPR000889. Glutathione_peroxidase.
IPR029759. GPX_AS.
IPR029760. GPX_CS.
IPR012336. Thioredoxin-like_fold.
[Graphical view]
PANTHERiPTHR11592. PTHR11592. 1 hit.
PfamiPF00255. GSHPx. 1 hit.
[Graphical view]
PIRSFiPIRSF000303. Glutathion_perox. 1 hit.
PRINTSiPR01011. GLUTPROXDASE.
SUPFAMiSSF52833. SSF52833. 1 hit.
PROSITEiPS00460. GLUTATHIONE_PEROXID_1. 1 hit.
PS00763. GLUTATHIONE_PEROXID_2. 1 hit.
PS51355. GLUTATHIONE_PEROXID_3. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "Cloning and sequencing of the cDNA encoding a phospholipid hydroperoxide glutathione peroxidase."
    Nam S.-Y., Nakamuta N., Kurohmaru M., Hayashi Y.
    Gene 198:245-249(1997) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].
    Strain: CD-1.
    Tissue: Testis.
  2. "Cloning of the mouse phospholipid hydroperoxide glutathione peroxidase gene."
    Borchert A., Schnurr K., Thiele B.J., Kuehn H.
    FEBS Lett. 446:223-227(1999) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
    Strain: C57BL/6N.
  3. "Murine phospholipid hydroperoxide glutathione peroxidase: cDNA sequence, tissue expression, and mapping."
    Knopp E.A., Arndt T.L., Eng K.L., Caldwell M., LeBoeuf R.C., Deeb S.S., O'Brien K.D.
    Mamm. Genome 10:601-605(1999) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA].
    Strain: BALB/c and C57BL/6J.
    Tissue: Myocardium and Testis.
  4. Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
    Strain: 129/SvJ.
    Tissue: Liver.
  5. "The transcriptional landscape of the mammalian genome."
    Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.
    , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.
    Science 309:1559-1563(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
    Strain: C57BL/6J.
    Tissue: Testis.
  6. "The selenoprotein GPX4 is essential for mouse development and protects from radiation and oxidative damage insults."
    Yant L.J., Ran Q., Rao L., Van Remmen H., Shibatani T., Belter J.G., Motta L., Richardson A., Prolla T.A.
    Free Radic. Biol. Med. 34:496-502(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION.
  7. "Glutathione peroxidase 4 senses and translates oxidative stress into 12/15-lipoxygenase dependent- and AIF-mediated cell death."
    Seiler A., Schneider M., Foerster H., Roth S., Wirth E.K., Culmsee C., Plesnila N., Kremmer E., Raadmark O., Wurst W., Bornkamm G.W., Schweizer U., Conrad M.
    Cell Metab. 8:237-248(2008) [PubMed] [Europe PMC] [Abstract]
    Cited for: DISRUPTION PHENOTYPE, FUNCTION.
  8. Cited for: DISRUPTION PHENOTYPE, FUNCTION, TISSUE SPECIFICITY.

Entry informationi

Entry nameiGPX41_MOUSE
AccessioniPrimary (citable) accession number: O70325
Secondary accession number(s): O35560, Q9JK35
Entry historyi
Integrated into UniProtKB/Swiss-Prot: January 11, 2001
Last sequence update: February 26, 2008
Last modified: February 4, 2015
This is version 141 of the entry and version 4 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into Uniref entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.