O70325 (GPX41_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended 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

Organism

Mus musculus (Mouse) [Reference proteome]

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › Mus

Protein attributes

Sequence length	197 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	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. 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 mitochondrial causes sperm abnormalities and male infertility. Ref.7 Ref.8
Sequence similarities	Belongs to the glutathione peroxidase family.

Ontologies

Keywords
Cellular component	Cytoplasm Mitochondrion
Coding sequence diversity	Alternative initiation Alternative splicing Selenocysteine
Domain	Transit peptide
Molecular function	Developmental protein Oxidoreductase Peroxidase
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	chromatin organization Inferred from direct assay PubMed 11344099. Source: MGI multicellular organismal development Inferred from electronic annotation. Source: UniProtKB-KW response to oxidative stress Inferred from electronic annotation. Source: InterPro spermatogenesis Inferred from direct assay PubMed 11344099. Source: MGI
Cellular_component	cytosol Inferred from direct assay Ref.6. Source: MGI mitochondrial inner membrane Inferred from direct assay PubMed 12865426. Source: MGI nuclear envelope Inferred from direct assay Ref.6. Source: MGI
Molecular_function	glutathione peroxidase activity Inferred from direct assay PubMed 11344099. Source: MGI phospholipid-hydroperoxide glutathione peroxidase activity Inferred from electronic annotation. Source: EC
Complete GO annotation...

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 key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Transit peptide	1 – ?		Mitochondrion Potential
	Chain	? – 197		Phospholipid hydroperoxide glutathione peroxidase, mitochondrial		PRO_0000013069
Sites
	Active site	73	1
Amino acid modifications
	Non-standard residue	73	1	Selenocysteine
Natural variations
	Alternative sequence	1 – 27	27	Missing in isoform Cytoplasmic.		VSP_018743
Experimental info
	Sequence conflict	39	1	R → A in BAA22780. Ref.1

Sequences

	Sequence		Length	Mass (Da)
	Isoform Mitochondrial [UniParc]. Last modified February 26, 2008. Version 4. Checksum: 5CED4991A484F31C	FASTA	197	22,229
	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
	Isoform Nuclear [UniParc]. See Q91XR9.		–	–
	Isoform Cytoplasmic [UniParc]. Checksum: 89AD1F6B28946C95	FASTA	170	19,522
	10 20 30 40 50 60 MCASRDDWRC ARSMHEFSAK DIDGHMVCLD KYRGFVCIVT NVASQUGKTD VNYTQLVDLH 70 80 90 100 110 120 ARYAECGLRI LAFPCNQFGR QEPGSNQEIK EFAAGYNVKF DMYSKICVNG DDAHPLWKWM 130 140 150 160 170 KVQPKGRGML GNAIKWNFTK FLIDKNGCVV KRYGPMEEPQ VIEKDLPCYL

References

	« Hide 'large scale' referencesShow '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. , 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.
IPI	IPI00117281. IPI00989123.
RefSeq	NP_001032830.2. NM_001037741.2. NP_032188.3. NM_008162.2.
UniGene	Mm.359573.
3D structure databases
ProteinModelPortal	O70325.
SMR	O70325. Positions 33-197.
ModBase	Search...
Protein-protein interaction databases
IntAct	O70325. 1 interaction.
Protein family/group databases
PeroxiBase	3714. MmGPx04-A. 3867. MmGPx04-C.
Proteomic databases
PaxDb	O70325.
PRIDE	O70325.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENSMUST00000105372; ENSMUSP00000101011; ENSMUSG00000075706.
GeneID	625249.
KEGG	mmu:625249.
Organism-specific databases
CTD	2879.
MGI	MGI:104767. Gpx4.
Phylogenomic databases
eggNOG	COG0386.
GeneTree	ENSGT00550000074312.
HOGENOM	HOG000277054.
HOVERGEN	HBG004333.
KO	K05361.
OMA	SKMKPED.
OrthoDB	EOG4K3KXQ.
Gene expression databases
Bgee	O70325.
CleanEx	MM_GPX4.
Genevestigator	O70325.
GermOnline	ENSMUSG00000065948. Mus musculus.
Family and domain databases
Gene3D	3.40.30.10. 1 hit.
InterPro	IPR000889. Glutathione_peroxidase. IPR012336. Thioredoxin-like_fold. [Graphical view]
PANTHER	PTHR11592. PTHR11592. 1 hit.
Pfam	PF00255. GSHPx. 1 hit. [Graphical view]
PIRSF	PIRSF000303. Glutathion_perox. 1 hit.
PRINTS	PR01011. GLUTPROXDASE.
SUPFAM	SSF52833. Thiordxn-like_fd. 1 hit.
PROSITE	PS00460. GLUTATHIONE_PEROXID_1. 1 hit. PS00763. GLUTATHIONE_PEROXID_2. 1 hit. PS51355. GLUTATHIONE_PEROXID_3. 1 hit. [Graphical view]
ProtoNet	Search...
Other
ChiTaRS	GPX4. mouse.
NextBio	418158.
SOURCE	Search...

Entry information

Entry name

GPX41_MOUSE

Accession

Primary (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:	April 3, 2013
This is version 124 of the entry and version 4 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program