ID   GPX41_MOUSE             Reviewed;         197 AA.
AC   O70325; O35560; Q9JK35;
DT   11-JAN-2001, integrated into UniProtKB/Swiss-Prot.
DT   26-FEB-2008, sequence version 4.
DT   16-JUN-2009, entry version 89.
DE   RecName: Full=Phospholipid hydroperoxide glutathione peroxidase, mitochondrial;
DE            Short=PHGPx;
DE            EC=1.11.1.12;
DE   AltName: Full=GPX-4;
DE   Flags: Precursor;
GN   Name=Gpx4;
OS   Mus musculus (Mouse).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC   Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Sciurognathi;
OC   Muroidea; Muridae; Murinae; Mus.
OX   NCBI_TaxID=10090;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RC   STRAIN=CD-1; TISSUE=Testis;
RX   MEDLINE=98036055; PubMed=9370288; DOI=10.1016/S0378-1119(97)00321-1;
RA   Nam S.-Y., Nakamuta N., Kurohmaru M., Hayashi Y.;
RT   "Cloning and sequencing of the cDNA encoding a phospholipid
RT   hydroperoxide glutathione peroxidase.";
RL   Gene 198:245-249(1997).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC   STRAIN=C57BL/6N;
RX   MEDLINE=99198944; PubMed=10100845; DOI=10.1016/S0014-5793(99)00221-5;
RA   Borchert A., Schnurr K., Thiele B.J., Kuehn H.;
RT   "Cloning of the mouse phospholipid hydroperoxide glutathione
RT   peroxidase gene.";
RL   FEBS Lett. 446:223-227(1999).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA].
RC   STRAIN=BALB/c, and C57BL/6J; TISSUE=Myocardium, and Testis;
RX   MEDLINE=99272820; PubMed=10341094; DOI=10.1007/s003359901053;
RA   Knopp E.A., Arndt T.L., Eng K.L., Caldwell M., LeBoeuf R.C.,
RA   Deeb S.S., O'Brien K.D.;
RT   "Murine phospholipid hydroperoxide glutathione peroxidase: cDNA
RT   sequence, tissue expression, and mapping.";
RL   Mamm. Genome 10:601-605(1999).
RN   [4]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC   STRAIN=129/SvJ; TISSUE=Liver;
RX   MEDLINE=22630150; PubMed=12745070; DOI=10.1016/S0006-291X(03)00734-4;
RA   Imai H., Hirao F., Sakamoto T., Sekine K., Mizukura Y., Saito M.,
RA   Kitamoto T., Hayasaka M., Hanaoka K., Nakagawa Y.;
RT   "Early embryonic lethality caused by targeted disruption of the mouse
RT   PHGPx gene.";
RL   Biochem. Biophys. Res. Commun. 305:278-286(2003).
RN   [5]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   STRAIN=C57BL/6J; TISSUE=Testis;
RX   PubMed=16141072; DOI=10.1126/science.1112014;
RA   Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA   Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA   Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M.,
RA   Davis M.J., Wilming L.G., Aidinis V., Allen J.E.,
RA   Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L.,
RA   Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M.,
RA   Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R.,
RA   Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G.,
RA   di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G.,
RA   Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M.,
RA   Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA   Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N.,
RA   Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T.,
RA   Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H.,
RA   Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K.,
RA   Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J.,
RA   Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L.,
RA   Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K.,
RA   Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P.,
RA   Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O.,
RA   Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G.,
RA   Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M.,
RA   Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA   Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA   Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B.,
RA   Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K.,
RA   Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A.,
RA   Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K.,
RA   Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C.,
RA   Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J.,
RA   Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y.,
RA   Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T.,
RA   Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N.,
RA   Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N.,
RA   Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S.,
RA   Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J.,
RA   Hayashizaki Y.;
RT   "The transcriptional landscape of the mammalian genome.";
RL   Science 309:1559-1563(2005).
RN   [6]
RP   FUNCTION.
RX   MEDLINE=22453509; PubMed=12566075; DOI=10.1016/S0891-5849(02)01360-6;
RA   Yant L.J., Ran Q., Rao L., Van Remmen H., Shibatani T., Belter J.G.,
RA   Motta L., Richardson A., Prolla T.A.;
RT   "The selenoprotein GPX4 is essential for mouse development and
RT   protects from radiation and oxidative damage insults.";
RL   Free Radic. Biol. Med. 34:496-502(2003).
RN   [7]
RP   DISRUPTION PHENOTYPE, AND FUNCTION.
RX   PubMed=18762024; DOI=10.1016/j.cmet.2008.07.005;
RA   Seiler A., Schneider M., Foerster H., Roth S., Wirth E.K., Culmsee C.,
RA   Plesnila N., Kremmer E., Raadmark O., Wurst W., Bornkamm G.W.,
RA   Schweizer U., Conrad M.;
RT   "Glutathione peroxidase 4 senses and translates oxidative stress into
RT   12/15-lipoxygenase dependent- and AIF-mediated cell death.";
RL   Cell Metab. 8:237-248(2008).
RN   [8]
RP   DISRUPTION PHENOTYPE, FUNCTION, AND TISSUE SPECIFICITY.
RX   PubMed=19417079; DOI=10.1096/fj.09-132795;
RA   Schneider M., Foerster H., Boersma A., Seiler A., Wehnes H.,
RA   Sinowatz F., Neumueller C., Deutsch M.J., Walch A.,
RA   Hrabe de Angelis M., Wurst W., Ursini F., Roveri A., Maleszewski M.,
RA   Maiorino M., Conrad M.;
RT   "Mitochondrial glutathione peroxidase 4 disruption causes male
RT   infertility.";
RL   FASEB J. 0:0-0(2009).
CC   -!- FUNCTION: Protects cells against membrane lipid peroxidation and
CC       cell death. Isoform mitochondrial is required for normal sperm
CC       development and male fertility. Could play a major role in
CC       protecting mammals from the toxicity of ingested lipid
CC       hydroperoxides. Essential for embryonic development. Protects from
CC       radiation and oxidative damage.
CC   -!- CATALYTIC ACTIVITY: 2 glutathione + a lipid hydroperoxide =
CC       glutathione disulfide + lipid + 2 H(2)O.
CC   -!- SUBUNIT: Monomer (By similarity).
CC   -!- SUBCELLULAR LOCATION: Mitochondrion. Cytoplasm.
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Alternative splicing, Alternative initiation; Named isoforms=3;
CC       Name=Mitochondrial;
CC         IsoId=O70325-1; Sequence=Displayed;
CC       Name=Nuclear;
CC         IsoId=Q91XR9-1; Sequence=External;
CC       Name=Cytoplasmic;
CC         IsoId=O70325-2; Sequence=VSP_018743;
CC         Note=Produced by alternative initiation at Met-28 of isoform
CC         Mitochondrial;
CC   -!- TISSUE SPECIFICITY: Detected in testis and sperm midpiece (at
CC       protein level). Present primarily in testis.
CC   -!- DISRUPTION PHENOTYPE: Embryonic lethality. The embryos die after
CC       about 7.5 days of development. Causes neurodegeneration. Selective
CC       disruption of isoform mitochondrial causes sperm abnormalities and
CC       male infertility.
CC   -!- SIMILARITY: Belongs to the glutathione peroxidase family.
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DR   EMBL; D87896; BAA22780.1; -; mRNA.
DR   EMBL; AJ012104; CAB42657.2; -; Genomic_DNA.
DR   EMBL; AF045768; AAC15832.1; -; mRNA.
DR   EMBL; AF045769; AAC15833.1; -; mRNA.
DR   EMBL; AF044056; AAC14560.1; -; Genomic_DNA.
DR   EMBL; AB030643; BAC06507.1; -; Genomic_DNA.
DR   EMBL; AB030643; BAC06508.1; -; Genomic_DNA.
DR   EMBL; AB030728; BAC06511.1; -; Genomic_DNA.
DR   EMBL; AK006441; BAC55251.1; -; mRNA.
DR   IPI; IPI00117281; -.
DR   IPI; IPI00919204; -.
DR   RefSeq; NP_032188.3; -.
DR   UniGene; Mm.359573; -.
DR   HSSP; P00435; 1GP1.
DR   SMR; O70325; 36-197.
DR   PeroxiBase; 3714; MmGPx04-a.
DR   PeroxiBase; 3867; MmGPx04-c.
DR   Ensembl; ENSMUSG00000075706; Mus musculus.
DR   GeneID; 625249; -.
DR   MGI; MGI:104767; Gpx4.
DR   HOGENOM; O70325; -.
DR   HOVERGEN; O70325; -.
DR   OMA; O70325; AQNGNDL.
DR   BRENDA; 1.11.1.12; 244.
DR   NextBio; 418158; -.
DR   Bgee; O70325; -.
DR   CleanEx; MM_GPX4; -.
DR   GermOnline; ENSMUSG00000065948; Mus musculus.
DR   GO; GO:0005829; C:cytosol; IDA:MGI.
DR   GO; GO:0005743; C:mitochondrial inner membrane; IDA:MGI.
DR   GO; GO:0005635; C:nuclear envelope; IDA:MGI.
DR   GO; GO:0004602; F:glutathione peroxidase activity; IDA:MGI.
DR   GO; GO:0047066; F:phospholipid-hydroperoxide glutathione pero...; IEA:EC.
DR   GO; GO:0008430; F:selenium binding; IEA:UniProtKB-KW.
DR   GO; GO:0006325; P:establishment or maintenance of chromatin a...; IDA:MGI.
DR   GO; GO:0007275; P:multicellular organismal development; IEA:UniProtKB-KW.
DR   GO; GO:0055114; P:oxidation reduction; IEA:UniProtKB-KW.
DR   GO; GO:0007283; P:spermatogenesis; IDA:MGI.
DR   InterPro; IPR000889; Glutathione_peroxidase.
DR   InterPro; IPR012335; Thioredoxin_fold.
DR   Gene3D; G3DSA:3.40.30.10; Thioredoxin_fold; 1.
DR   PANTHER; PTHR11592; Glut_peroxidase; 1.
DR   Pfam; PF00255; GSHPx; 1.
DR   PIRSF; PIRSF000303; Glutathion_perox; 1.
DR   PRINTS; PR01011; GLUTPROXDASE.
DR   PROSITE; PS00460; GLUTATHIONE_PEROXID_1; 1.
DR   PROSITE; PS00763; GLUTATHIONE_PEROXID_2; 1.
DR   PROSITE; PS51355; GLUTATHIONE_PEROXID_3; 1.
PE   1: Evidence at protein level;
KW   Alternative initiation; Alternative splicing; Cytoplasm;
KW   Developmental protein; Mitochondrion; Oxidoreductase; Peroxidase;
KW   Selenium; Selenocysteine; Transit peptide.
FT   TRANSIT       1      ?       Mitochondrion (Potential).
FT   CHAIN         ?    197       Phospholipid hydroperoxide glutathione
FT                                peroxidase, mitochondrial.
FT                                /FTId=PRO_0000013069.
FT   ACT_SITE     73     73
FT   NON_STD      73     73       Selenocysteine.
FT   VAR_SEQ       1     27       Missing (in isoform Cytoplasmic).
FT                                /FTId=VSP_018743.
FT   CONFLICT     39     39       R -> A (in Ref. 1; BAA22780).
SQ   SEQUENCE   197 AA;  22229 MW;  5CED4991A484F31C CRC64;
     MSWGRLSRLL KPALLCGALA APGLAGTMCA SRDDWRCARS MHEFSAKDID GHMVCLDKYR
     GFVCIVTNVA SQUGKTDVNY TQLVDLHARY AECGLRILAF PCNQFGRQEP GSNQEIKEFA
     AGYNVKFDMY SKICVNGDDA HPLWKWMKVQ PKGRGMLGNA IKWNFTKFLI DKNGCVVKRY
     GPMEEPQVIE KDLPCYL
//