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O70325 (GPX41_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 135. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (2) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Phospholipid hydroperoxide glutathione peroxidase, mitochondrial

Short name=PHGPx
EC=1.11.1.12
Alternative name(s):
Glutathione peroxidase 4
Short name=GPx-4
Short name=GSHPx-4
Gene names
Name:Gpx4
OrganismMus musculus (Mouse) [Reference proteome]
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus

Protein attributes

Sequence length197 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Protects cells against membrane lipid peroxidation and cell death. Isoform mitochondrialis 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. Ref.6 Ref.7 Ref.8

Catalytic activity

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

Subunit structure

Monomer By similarity.

Subcellular location

Mitochondrion. Cytoplasm.

Tissue specificity

Detected in testis and sperm midpiece (at protein level). Present primarily in testis. Ref.8

Disruption phenotype

Embryonic lethality. The embryos die after about 7.5 days of development. Causes neurodegeneration. Selective disruption of isoform mitochondrialcauses sperm abnormalities and male infertility. Ref.7 Ref.8

Sequence similarities

Belongs to the glutathione peroxidase family.

Alternative products

This entry describes 3 isoforms produced by alternative splicing and alternative initiation. [Align] [Select]
Isoform Mitochondrial (identifier: O70325-1)

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.
Isoform Nuclear (identifier: Q91XR9-1)

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.
Isoform Cytoplasmic (identifier: O70325-2)

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.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Transit peptide1 – ?Mitochondrion Potential
Chain? – 197Phospholipid hydroperoxide glutathione peroxidase, mitochondrialPRO_0000013069

Sites

Active site731

Amino acid modifications

Non-standard residue731Selenocysteine

Natural variations

Alternative sequence1 – 2727Missing in isoform Cytoplasmic.
VSP_018743

Experimental info

Sequence conflict391R → A in BAA22780. Ref.1

Sequences

Sequence LengthMass (Da)Tools
Isoform Mitochondrial [UniParc].

Last modified February 26, 2008. Version 4.
Checksum: 5CED4991A484F31C

FASTA19722,229
        10         20         30         40         50         60 
MSWGRLSRLL KPALLCGALA APGLAGTMCA SRDDWRCARS MHEFSAKDID GHMVCLDKYR 

        70         80         90        100        110        120 
GFVCIVTNVA SQUGKTDVNY TQLVDLHARY AECGLRILAF PCNQFGRQEP GSNQEIKEFA 

       130        140        150        160        170        180 
AGYNVKFDMY SKICVNGDDA HPLWKWMKVQ PKGRGMLGNA IKWNFTKFLI DKNGCVVKRY 

       190 
GPMEEPQVIE KDLPCYL 

« Hide

Isoform Nuclear [UniParc].

See Q91XR9.

Isoform Cytoplasmic [UniParc].

Checksum: 89AD1F6B28946C95
Show »

FASTA17019,522

References

« Hide 'large scale' references
[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]"Early embryonic lethality caused by targeted disruption of the mouse PHGPx gene."
Imai H., Hirao F., Sakamoto T., Sekine K., Mizukura Y., Saito M., Kitamoto T., Hayasaka M., Hanaoka K., Nakagawa Y.
Biochem. Biophys. Res. Commun. 305:278-286(2003) [PubMed] [Europe PMC] [Abstract]
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. expand/collapse author list , 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]"Mitochondrial glutathione peroxidase 4 disruption causes male infertility."
Schneider M., Forster H., Boersma A., Seiler A., Wehnes H., Sinowatz F., Neumueller C., Deutsch M.J., Walch A., Hrabe de Angelis M., Wurst W., Ursini F., Roveri A., Maleszewski M., Maiorino M., Conrad M.
FASEB J. 23:3233-3242(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: DISRUPTION PHENOTYPE, FUNCTION, TISSUE SPECIFICITY.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
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.
CCDSCCDS35973.1. [O70325-1]
RefSeqNP_001032830.2. NM_001037741.3.
NP_032188.3. NM_008162.3. [O70325-1]
UniGeneMm.332810.
Mm.359573.

3D structure databases

ProteinModelPortalO70325.
SMRO70325. Positions 33-197.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid551619. 1 interaction.
IntActO70325. 1 interaction.

Protein family/group databases

PeroxiBase3714. MmGPx04-A.
3867. MmGPx04-C.

Proteomic databases

PaxDbO70325.
PRIDEO70325.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSMUST00000105372; ENSMUSP00000101011; ENSMUSG00000075706. [O70325-1]
GeneID625249.
KEGGmmu:625249.
UCSCuc007gbk.1. mouse. [O70325-1]

Organism-specific databases

CTD2879.
MGIMGI:104767. Gpx4.

Phylogenomic databases

eggNOGCOG0386.
GeneTreeENSGT00740000115371.
HOGENOMHOG000277054.
HOVERGENHBG004333.
KOK05361.
OMALVDKNGC.
OrthoDBEOG7B5WZH.

Gene expression databases

BgeeO70325.
CleanExMM_GPX4.
GenevestigatorO70325.

Family and domain databases

Gene3D3.40.30.10. 1 hit.
InterProIPR000889. Glutathione_peroxidase.
IPR012336. Thioredoxin-like_fold.
[Graphical view]
PANTHERPTHR11592. PTHR11592. 1 hit.
PfamPF00255. GSHPx. 1 hit.
[Graphical view]
PIRSFPIRSF000303. Glutathion_perox. 1 hit.
PRINTSPR01011. GLUTPROXDASE.
SUPFAMSSF52833. SSF52833. 1 hit.
PROSITEPS00460. GLUTATHIONE_PEROXID_1. 1 hit.
PS00763. GLUTATHIONE_PEROXID_2. 1 hit.
PS51355. GLUTATHIONE_PEROXID_3. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSGPX4. mouse.
NextBio418158.
PROO70325.
SOURCESearch...

Entry information

Entry nameGPX41_MOUSE
AccessionPrimary (citable) accession number: O70325
Secondary accession number(s): O35560, Q9JK35
Entry history
Integrated into UniProtKB/Swiss-Prot: January 11, 2001
Last sequence update: February 26, 2008
Last modified: July 9, 2014
This is version 135 of the entry and version 4 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

MGD cross-references

Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot