Full text data of GPX4
GPX4
[Confidence: medium (present in either hRBCD or BSc_CH or PM22954596)]
Phospholipid hydroperoxide glutathione peroxidase, mitochondrial; PHGPx; 1.11.1.12 (Glutathione peroxidase 4; GPx-4; GSHPx-4; Flags: Precursor)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
Phospholipid hydroperoxide glutathione peroxidase, mitochondrial; PHGPx; 1.11.1.12 (Glutathione peroxidase 4; GPx-4; GSHPx-4; Flags: Precursor)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
UniProt
P36969
ID GPX4_HUMAN Reviewed; 197 AA.
AC P36969; O43381; Q6PJ59; Q9UPK2;
DT 01-JUN-1994, integrated into UniProtKB/Swiss-Prot.
read moreDT 26-FEB-2008, sequence version 3.
DT 22-JAN-2014, entry version 147.
DE RecName: Full=Phospholipid hydroperoxide glutathione peroxidase, mitochondrial;
DE Short=PHGPx;
DE EC=1.11.1.12;
DE AltName: Full=Glutathione peroxidase 4;
DE Short=GPx-4;
DE Short=GSHPx-4;
DE Flags: Precursor;
GN Name=GPX4;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Testis;
RX PubMed=8039723; DOI=10.1016/0378-1119(94)90400-6;
RA Esworthy R.S., Doan K., Doroshow J.H., Chu F.-F.;
RT "Cloning and sequencing of the cDNA encoding a human testis
RT phospholipid hydroperoxide glutathione peroxidase.";
RL Gene 144:317-318(1994).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=9705830; DOI=10.1006/bbrc.1998.9086;
RA Kelner M.J., Montoya M.A.;
RT "Structural organization of the human selenium-dependent phospholipid
RT hydroperoxide glutathione peroxidase gene (GPX4): chromosomal
RT localization to 19p13.3.";
RL Biochem. Biophys. Res. Commun. 249:53-55(1998).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANT ASN-2.
RG NIEHS SNPs program;
RL Submitted (JUN-2003) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15057824; DOI=10.1038/nature02399;
RA Grimwood J., Gordon L.A., Olsen A.S., Terry A., Schmutz J.,
RA Lamerdin J.E., Hellsten U., Goodstein D., Couronne O., Tran-Gyamfi M.,
RA Aerts A., Altherr M., Ashworth L., Bajorek E., Black S., Branscomb E.,
RA Caenepeel S., Carrano A.V., Caoile C., Chan Y.M., Christensen M.,
RA Cleland C.A., Copeland A., Dalin E., Dehal P., Denys M., Detter J.C.,
RA Escobar J., Flowers D., Fotopulos D., Garcia C., Georgescu A.M.,
RA Glavina T., Gomez M., Gonzales E., Groza M., Hammon N., Hawkins T.,
RA Haydu L., Ho I., Huang W., Israni S., Jett J., Kadner K., Kimball H.,
RA Kobayashi A., Larionov V., Leem S.-H., Lopez F., Lou Y., Lowry S.,
RA Malfatti S., Martinez D., McCready P.M., Medina C., Morgan J.,
RA Nelson K., Nolan M., Ovcharenko I., Pitluck S., Pollard M.,
RA Popkie A.P., Predki P., Quan G., Ramirez L., Rash S., Retterer J.,
RA Rodriguez A., Rogers S., Salamov A., Salazar A., She X., Smith D.,
RA Slezak T., Solovyev V., Thayer N., Tice H., Tsai M., Ustaszewska A.,
RA Vo N., Wagner M., Wheeler J., Wu K., Xie G., Yang J., Dubchak I.,
RA Furey T.S., DeJong P., Dickson M., Gordon D., Eichler E.E.,
RA Pennacchio L.A., Richardson P., Stubbs L., Rokhsar D.S., Myers R.M.,
RA Rubin E.M., Lucas S.M.;
RT "The DNA sequence and biology of human chromosome 19.";
RL Nature 428:529-535(2004).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain, Eye, Lung, Pancreas, and Testis;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [6]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P.,
RA Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [7]
RP X-RAY CRYSTALLOGRAPHY (1.55 ANGSTROMS) OF 29-197 (ISOFORM
RP CYTOPLASMIC), SUBUNIT, AND MUTAGENESIS OF SEC-73.
RX PubMed=17630701; DOI=10.1021/bi700840d;
RA Scheerer P., Borchert A., Krauss N., Wessner H., Gerth C., Hoehne W.,
RA Kuhn H.;
RT "Structural basis for catalytic activity and enzyme polymerization of
RT phospholipid hydroperoxide glutathione peroxidase-4 (GPx4).";
RL Biochemistry 46:9041-9049(2007).
RN [8]
RP X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS) OF 36-197.
RG Structural genomics consortium (SGC);
RT "Crystal structure of the selenocysteine to glycine mutant of human
RT glutathione peroxidase 4 (GPX4).";
RL Submitted (FEB-2009) to the PDB data bank.
RN [9]
RP VARIANTS ASN-2 AND THR-120.
RX PubMed=12606444; DOI=10.1095/biolreprod.102.007500;
RA Maiorino M., Bosello V., Ursini F., Foresta C., Garolla A., Scapin M.,
RA Sztajer H., Flohe L.;
RT "Genetic variations of gpx-4 and male infertility in humans.";
RL Biol. Reprod. 68:1134-1141(2003).
CC -!- FUNCTION: Protects cells against membrane lipid peroxidation and
CC cell death. Required for normal sperm development and male
CC fertility. Could play a major role in protecting mammals from the
CC toxicity of ingested lipid hydroperoxides. Essential for embryonic
CC development. Protects from radiation and oxidative damage (By
CC similarity).
CC -!- CATALYTIC ACTIVITY: 2 glutathione + a lipid hydroperoxide =
CC glutathione disulfide + lipid + 2 H(2)O.
CC -!- SUBUNIT: Monomer. Has a tendency to form higher mass oligomers.
CC -!- SUBCELLULAR LOCATION: Isoform Mitochondrial: Mitochondrion.
CC -!- SUBCELLULAR LOCATION: Isoform Cytoplasmic: Cytoplasm.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative initiation; Named isoforms=2;
CC Name=Mitochondrial;
CC IsoId=P36969-1; Sequence=Displayed;
CC Name=Cytoplasmic;
CC IsoId=P36969-2; Sequence=VSP_018740;
CC -!- TISSUE SPECIFICITY: Present primarily in testis.
CC -!- SIMILARITY: Belongs to the glutathione peroxidase family.
CC -!- WEB RESOURCE: Name=NIEHS-SNPs;
CC URL="http://egp.gs.washington.edu/data/gpx4/";
CC -----------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution-NoDerivs License
CC -----------------------------------------------------------------------
DR EMBL; X71973; CAA50793.1; -; mRNA.
DR EMBL; AF060972; AAC32261.1; -; Genomic_DNA.
DR EMBL; AY324108; AAP72965.1; -; Genomic_DNA.
DR EMBL; AC004151; AAC03239.1; -; Genomic_DNA.
DR EMBL; AC005390; AAC28920.1; -; Genomic_DNA.
DR EMBL; BC011836; AAH11836.1; -; mRNA.
DR EMBL; BC021567; AAH21567.1; -; mRNA.
DR EMBL; BC022071; AAH22071.1; -; mRNA.
DR EMBL; BC032695; AAH32695.3; -; mRNA.
DR EMBL; BC039849; AAH39849.1; -; mRNA.
DR PIR; T02747; T02747.
DR RefSeq; NP_001034936.1; NM_001039847.1.
DR RefSeq; NP_001034937.1; NM_001039848.1.
DR RefSeq; NP_002076.2; NM_002085.3.
DR UniGene; Hs.433951; -.
DR PDB; 2GS3; X-ray; 1.90 A; A=36-197.
DR PDB; 2OBI; X-ray; 1.55 A; A=29-197.
DR PDBsum; 2GS3; -.
DR PDBsum; 2OBI; -.
DR ProteinModelPortal; P36969; -.
DR SMR; P36969; 33-197.
DR IntAct; P36969; 3.
DR STRING; 9606.ENSP00000346103; -.
DR DrugBank; DB00143; Glutathione.
DR PeroxiBase; 3603; HsGPx04-A.
DR PeroxiBase; 3632; HsGPx04-B.
DR PeroxiBase; 3633; HsGPx04-C.
DR PhosphoSite; P36969; -.
DR DMDM; 172045844; -.
DR REPRODUCTION-2DPAGE; IPI00304814; -.
DR UCD-2DPAGE; P36969; -.
DR PaxDb; P36969; -.
DR PRIDE; P36969; -.
DR DNASU; 2879; -.
DR Ensembl; ENST00000354171; ENSP00000346103; ENSG00000167468.
DR GeneID; 2879; -.
DR KEGG; hsa:2879; -.
DR UCSC; uc021umf.1; human.
DR CTD; 2879; -.
DR GeneCards; GC19P001103; -.
DR HGNC; HGNC:4556; GPX4.
DR HPA; CAB008630; -.
DR MIM; 138322; gene.
DR neXtProt; NX_P36969; -.
DR PharmGKB; PA28952; -.
DR eggNOG; COG0386; -.
DR HOGENOM; HOG000277054; -.
DR HOVERGEN; HBG004333; -.
DR InParanoid; P36969; -.
DR KO; K05361; -.
DR OrthoDB; EOG7B5WZH; -.
DR PhylomeDB; P36969; -.
DR BioCyc; MetaCyc:HS09562-MONOMER; -.
DR Reactome; REACT_111217; Metabolism.
DR SABIO-RK; P36969; -.
DR ChiTaRS; GPX4; human.
DR EvolutionaryTrace; P36969; -.
DR GeneWiki; GPX4; -.
DR GenomeRNAi; 2879; -.
DR NextBio; 11367; -.
DR PRO; PR:P36969; -.
DR ArrayExpress; P36969; -.
DR Bgee; P36969; -.
DR CleanEx; HS_GPX4; -.
DR Genevestigator; P36969; -.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0005739; C:mitochondrion; TAS:UniProtKB.
DR GO; GO:0004602; F:glutathione peroxidase activity; TAS:UniProtKB.
DR GO; GO:0047066; F:phospholipid-hydroperoxide glutathione peroxidase activity; IEA:UniProtKB-EC.
DR GO; GO:0019369; P:arachidonic acid metabolic process; TAS:Reactome.
DR GO; GO:0019372; P:lipoxygenase pathway; TAS:Reactome.
DR GO; GO:0007275; P:multicellular organismal development; IEA:UniProtKB-KW.
DR GO; GO:0006644; P:phospholipid metabolic process; TAS:UniProtKB.
DR GO; GO:0006979; P:response to oxidative stress; IEA:InterPro.
DR Gene3D; 3.40.30.10; -; 1.
DR InterPro; IPR000889; Glutathione_peroxidase.
DR InterPro; IPR012336; Thioredoxin-like_fold.
DR PANTHER; PTHR11592; PTHR11592; 1.
DR Pfam; PF00255; GSHPx; 1.
DR PIRSF; PIRSF000303; Glutathion_perox; 1.
DR SUPFAM; SSF52833; SSF52833; 1.
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 3D-structure; Alternative initiation; Complete proteome; Cytoplasm;
KW Developmental protein; Mitochondrion; Oxidoreductase; Peroxidase;
KW Polymorphism; Reference proteome; Selenocysteine; Transit peptide.
FT TRANSIT 1 ? Mitochondrion (Potential).
FT CHAIN ? 197 Phospholipid hydroperoxide glutathione
FT peroxidase, mitochondrial.
FT /FTId=PRO_0000013067.
FT ACT_SITE 73 73
FT NON_STD 73 73 Selenocysteine.
FT VAR_SEQ 1 27 Missing (in isoform Cytoplasmic).
FT /FTId=VSP_018740.
FT VARIANT 2 2 S -> N (in dbSNP:rs8178967).
FT /FTId=VAR_017063.
FT VARIANT 120 120 A -> T (in a patient affected by
FT cryptorchidism; dbSNP:rs76201145).
FT /FTId=VAR_017064.
FT MUTAGEN 73 73 U->A: Loss of enzyme activity.
FT MUTAGEN 73 73 U->C: Almost complete loss of enzyme
FT activity.
FT HELIX 35 37
FT HELIX 41 43
FT STRAND 45 48
FT STRAND 53 55
FT HELIX 56 59
FT STRAND 62 69
FT STRAND 71 73
FT HELIX 76 90
FT HELIX 91 93
FT STRAND 95 101
FT TURN 104 107
FT HELIX 113 121
FT TURN 122 124
FT STRAND 127 130
FT STRAND 134 137
FT HELIX 142 148
FT TURN 151 153
FT STRAND 156 160
FT STRAND 167 170
FT STRAND 176 180
FT HELIX 187 190
FT HELIX 194 196
SQ SEQUENCE 197 AA; 22175 MW; 1AE3BC7AE42FDDB1 CRC64;
MSLGRLCRLL KPALLCGALA APGLAGTMCA SRDDWRCARS MHEFSAKDID GHMVNLDKYR
GFVCIVTNVA SQUGKTEVNY TQLVDLHARY AECGLRILAF PCNQFGKQEP GSNEEIKEFA
AGYNVKFDMF SKICVNGDDA HPLWKWMKIQ PKGKGILGNA IKWNFTKFLI DKNGCVVKRY
GPMEEPLVIE KDLPHYF
//
ID GPX4_HUMAN Reviewed; 197 AA.
AC P36969; O43381; Q6PJ59; Q9UPK2;
DT 01-JUN-1994, integrated into UniProtKB/Swiss-Prot.
read moreDT 26-FEB-2008, sequence version 3.
DT 22-JAN-2014, entry version 147.
DE RecName: Full=Phospholipid hydroperoxide glutathione peroxidase, mitochondrial;
DE Short=PHGPx;
DE EC=1.11.1.12;
DE AltName: Full=Glutathione peroxidase 4;
DE Short=GPx-4;
DE Short=GSHPx-4;
DE Flags: Precursor;
GN Name=GPX4;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Testis;
RX PubMed=8039723; DOI=10.1016/0378-1119(94)90400-6;
RA Esworthy R.S., Doan K., Doroshow J.H., Chu F.-F.;
RT "Cloning and sequencing of the cDNA encoding a human testis
RT phospholipid hydroperoxide glutathione peroxidase.";
RL Gene 144:317-318(1994).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=9705830; DOI=10.1006/bbrc.1998.9086;
RA Kelner M.J., Montoya M.A.;
RT "Structural organization of the human selenium-dependent phospholipid
RT hydroperoxide glutathione peroxidase gene (GPX4): chromosomal
RT localization to 19p13.3.";
RL Biochem. Biophys. Res. Commun. 249:53-55(1998).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANT ASN-2.
RG NIEHS SNPs program;
RL Submitted (JUN-2003) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15057824; DOI=10.1038/nature02399;
RA Grimwood J., Gordon L.A., Olsen A.S., Terry A., Schmutz J.,
RA Lamerdin J.E., Hellsten U., Goodstein D., Couronne O., Tran-Gyamfi M.,
RA Aerts A., Altherr M., Ashworth L., Bajorek E., Black S., Branscomb E.,
RA Caenepeel S., Carrano A.V., Caoile C., Chan Y.M., Christensen M.,
RA Cleland C.A., Copeland A., Dalin E., Dehal P., Denys M., Detter J.C.,
RA Escobar J., Flowers D., Fotopulos D., Garcia C., Georgescu A.M.,
RA Glavina T., Gomez M., Gonzales E., Groza M., Hammon N., Hawkins T.,
RA Haydu L., Ho I., Huang W., Israni S., Jett J., Kadner K., Kimball H.,
RA Kobayashi A., Larionov V., Leem S.-H., Lopez F., Lou Y., Lowry S.,
RA Malfatti S., Martinez D., McCready P.M., Medina C., Morgan J.,
RA Nelson K., Nolan M., Ovcharenko I., Pitluck S., Pollard M.,
RA Popkie A.P., Predki P., Quan G., Ramirez L., Rash S., Retterer J.,
RA Rodriguez A., Rogers S., Salamov A., Salazar A., She X., Smith D.,
RA Slezak T., Solovyev V., Thayer N., Tice H., Tsai M., Ustaszewska A.,
RA Vo N., Wagner M., Wheeler J., Wu K., Xie G., Yang J., Dubchak I.,
RA Furey T.S., DeJong P., Dickson M., Gordon D., Eichler E.E.,
RA Pennacchio L.A., Richardson P., Stubbs L., Rokhsar D.S., Myers R.M.,
RA Rubin E.M., Lucas S.M.;
RT "The DNA sequence and biology of human chromosome 19.";
RL Nature 428:529-535(2004).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain, Eye, Lung, Pancreas, and Testis;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [6]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P.,
RA Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [7]
RP X-RAY CRYSTALLOGRAPHY (1.55 ANGSTROMS) OF 29-197 (ISOFORM
RP CYTOPLASMIC), SUBUNIT, AND MUTAGENESIS OF SEC-73.
RX PubMed=17630701; DOI=10.1021/bi700840d;
RA Scheerer P., Borchert A., Krauss N., Wessner H., Gerth C., Hoehne W.,
RA Kuhn H.;
RT "Structural basis for catalytic activity and enzyme polymerization of
RT phospholipid hydroperoxide glutathione peroxidase-4 (GPx4).";
RL Biochemistry 46:9041-9049(2007).
RN [8]
RP X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS) OF 36-197.
RG Structural genomics consortium (SGC);
RT "Crystal structure of the selenocysteine to glycine mutant of human
RT glutathione peroxidase 4 (GPX4).";
RL Submitted (FEB-2009) to the PDB data bank.
RN [9]
RP VARIANTS ASN-2 AND THR-120.
RX PubMed=12606444; DOI=10.1095/biolreprod.102.007500;
RA Maiorino M., Bosello V., Ursini F., Foresta C., Garolla A., Scapin M.,
RA Sztajer H., Flohe L.;
RT "Genetic variations of gpx-4 and male infertility in humans.";
RL Biol. Reprod. 68:1134-1141(2003).
CC -!- FUNCTION: Protects cells against membrane lipid peroxidation and
CC cell death. Required for normal sperm development and male
CC fertility. Could play a major role in protecting mammals from the
CC toxicity of ingested lipid hydroperoxides. Essential for embryonic
CC development. Protects from radiation and oxidative damage (By
CC similarity).
CC -!- CATALYTIC ACTIVITY: 2 glutathione + a lipid hydroperoxide =
CC glutathione disulfide + lipid + 2 H(2)O.
CC -!- SUBUNIT: Monomer. Has a tendency to form higher mass oligomers.
CC -!- SUBCELLULAR LOCATION: Isoform Mitochondrial: Mitochondrion.
CC -!- SUBCELLULAR LOCATION: Isoform Cytoplasmic: Cytoplasm.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative initiation; Named isoforms=2;
CC Name=Mitochondrial;
CC IsoId=P36969-1; Sequence=Displayed;
CC Name=Cytoplasmic;
CC IsoId=P36969-2; Sequence=VSP_018740;
CC -!- TISSUE SPECIFICITY: Present primarily in testis.
CC -!- SIMILARITY: Belongs to the glutathione peroxidase family.
CC -!- WEB RESOURCE: Name=NIEHS-SNPs;
CC URL="http://egp.gs.washington.edu/data/gpx4/";
CC -----------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution-NoDerivs License
CC -----------------------------------------------------------------------
DR EMBL; X71973; CAA50793.1; -; mRNA.
DR EMBL; AF060972; AAC32261.1; -; Genomic_DNA.
DR EMBL; AY324108; AAP72965.1; -; Genomic_DNA.
DR EMBL; AC004151; AAC03239.1; -; Genomic_DNA.
DR EMBL; AC005390; AAC28920.1; -; Genomic_DNA.
DR EMBL; BC011836; AAH11836.1; -; mRNA.
DR EMBL; BC021567; AAH21567.1; -; mRNA.
DR EMBL; BC022071; AAH22071.1; -; mRNA.
DR EMBL; BC032695; AAH32695.3; -; mRNA.
DR EMBL; BC039849; AAH39849.1; -; mRNA.
DR PIR; T02747; T02747.
DR RefSeq; NP_001034936.1; NM_001039847.1.
DR RefSeq; NP_001034937.1; NM_001039848.1.
DR RefSeq; NP_002076.2; NM_002085.3.
DR UniGene; Hs.433951; -.
DR PDB; 2GS3; X-ray; 1.90 A; A=36-197.
DR PDB; 2OBI; X-ray; 1.55 A; A=29-197.
DR PDBsum; 2GS3; -.
DR PDBsum; 2OBI; -.
DR ProteinModelPortal; P36969; -.
DR SMR; P36969; 33-197.
DR IntAct; P36969; 3.
DR STRING; 9606.ENSP00000346103; -.
DR DrugBank; DB00143; Glutathione.
DR PeroxiBase; 3603; HsGPx04-A.
DR PeroxiBase; 3632; HsGPx04-B.
DR PeroxiBase; 3633; HsGPx04-C.
DR PhosphoSite; P36969; -.
DR DMDM; 172045844; -.
DR REPRODUCTION-2DPAGE; IPI00304814; -.
DR UCD-2DPAGE; P36969; -.
DR PaxDb; P36969; -.
DR PRIDE; P36969; -.
DR DNASU; 2879; -.
DR Ensembl; ENST00000354171; ENSP00000346103; ENSG00000167468.
DR GeneID; 2879; -.
DR KEGG; hsa:2879; -.
DR UCSC; uc021umf.1; human.
DR CTD; 2879; -.
DR GeneCards; GC19P001103; -.
DR HGNC; HGNC:4556; GPX4.
DR HPA; CAB008630; -.
DR MIM; 138322; gene.
DR neXtProt; NX_P36969; -.
DR PharmGKB; PA28952; -.
DR eggNOG; COG0386; -.
DR HOGENOM; HOG000277054; -.
DR HOVERGEN; HBG004333; -.
DR InParanoid; P36969; -.
DR KO; K05361; -.
DR OrthoDB; EOG7B5WZH; -.
DR PhylomeDB; P36969; -.
DR BioCyc; MetaCyc:HS09562-MONOMER; -.
DR Reactome; REACT_111217; Metabolism.
DR SABIO-RK; P36969; -.
DR ChiTaRS; GPX4; human.
DR EvolutionaryTrace; P36969; -.
DR GeneWiki; GPX4; -.
DR GenomeRNAi; 2879; -.
DR NextBio; 11367; -.
DR PRO; PR:P36969; -.
DR ArrayExpress; P36969; -.
DR Bgee; P36969; -.
DR CleanEx; HS_GPX4; -.
DR Genevestigator; P36969; -.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0005739; C:mitochondrion; TAS:UniProtKB.
DR GO; GO:0004602; F:glutathione peroxidase activity; TAS:UniProtKB.
DR GO; GO:0047066; F:phospholipid-hydroperoxide glutathione peroxidase activity; IEA:UniProtKB-EC.
DR GO; GO:0019369; P:arachidonic acid metabolic process; TAS:Reactome.
DR GO; GO:0019372; P:lipoxygenase pathway; TAS:Reactome.
DR GO; GO:0007275; P:multicellular organismal development; IEA:UniProtKB-KW.
DR GO; GO:0006644; P:phospholipid metabolic process; TAS:UniProtKB.
DR GO; GO:0006979; P:response to oxidative stress; IEA:InterPro.
DR Gene3D; 3.40.30.10; -; 1.
DR InterPro; IPR000889; Glutathione_peroxidase.
DR InterPro; IPR012336; Thioredoxin-like_fold.
DR PANTHER; PTHR11592; PTHR11592; 1.
DR Pfam; PF00255; GSHPx; 1.
DR PIRSF; PIRSF000303; Glutathion_perox; 1.
DR SUPFAM; SSF52833; SSF52833; 1.
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 3D-structure; Alternative initiation; Complete proteome; Cytoplasm;
KW Developmental protein; Mitochondrion; Oxidoreductase; Peroxidase;
KW Polymorphism; Reference proteome; Selenocysteine; Transit peptide.
FT TRANSIT 1 ? Mitochondrion (Potential).
FT CHAIN ? 197 Phospholipid hydroperoxide glutathione
FT peroxidase, mitochondrial.
FT /FTId=PRO_0000013067.
FT ACT_SITE 73 73
FT NON_STD 73 73 Selenocysteine.
FT VAR_SEQ 1 27 Missing (in isoform Cytoplasmic).
FT /FTId=VSP_018740.
FT VARIANT 2 2 S -> N (in dbSNP:rs8178967).
FT /FTId=VAR_017063.
FT VARIANT 120 120 A -> T (in a patient affected by
FT cryptorchidism; dbSNP:rs76201145).
FT /FTId=VAR_017064.
FT MUTAGEN 73 73 U->A: Loss of enzyme activity.
FT MUTAGEN 73 73 U->C: Almost complete loss of enzyme
FT activity.
FT HELIX 35 37
FT HELIX 41 43
FT STRAND 45 48
FT STRAND 53 55
FT HELIX 56 59
FT STRAND 62 69
FT STRAND 71 73
FT HELIX 76 90
FT HELIX 91 93
FT STRAND 95 101
FT TURN 104 107
FT HELIX 113 121
FT TURN 122 124
FT STRAND 127 130
FT STRAND 134 137
FT HELIX 142 148
FT TURN 151 153
FT STRAND 156 160
FT STRAND 167 170
FT STRAND 176 180
FT HELIX 187 190
FT HELIX 194 196
SQ SEQUENCE 197 AA; 22175 MW; 1AE3BC7AE42FDDB1 CRC64;
MSLGRLCRLL KPALLCGALA APGLAGTMCA SRDDWRCARS MHEFSAKDID GHMVNLDKYR
GFVCIVTNVA SQUGKTEVNY TQLVDLHARY AECGLRILAF PCNQFGKQEP GSNEEIKEFA
AGYNVKFDMF SKICVNGDDA HPLWKWMKIQ PKGKGILGNA IKWNFTKFLI DKNGCVVKRY
GPMEEPLVIE KDLPHYF
//
MIM
138322
*RECORD*
*FIELD* NO
138322
*FIELD* TI
*138322 GLUTATHIONE PEROXIDASE 4; GPX4
;;PHOSPHOLIPID HYDROPEROXIDE GLUTATHIONE PEROXIDASE; PHGPX
read more*FIELD* TX
DESCRIPTION
GPX4 reduces phospholipid hydroperoxides within membranes and
lipoproteins and acts in conjunction with alpha-tocopherol to inhibit
lipid peroxidation. Lipid peroxidation is implicated in a number of
pathophysiologic processes, including inflammation and atherogenesis.
GPX4 is a selenoprotein whose production and activity are sensitive to
selenium (Se), which is incorporated into selenoproteins as
selenocysteine (summary by Sneddon et al., 2003).
CLONING
Using porcine Phgpx to screen a testis cDNA library, Esworthy et al.
(1994) cloned human GPX4, which they called PHGPX. The 3-prime UTR
contains a selenocysteine insertion sequence (SECIS) required for
insertion of selenocysteine at an opal codon (UGA). The deduced
197-amino acid protein has a calculated molecular mass of 19 kD. It has
putative active-site tryptophan and glutamic acid residues that are
predicted to interact with selenocysteine, and a tyrosine residue that
is phosphorylated in the porcine protein.
By fractionation and immunofluorescence microscopy of resting human
platelets, Januel et al. (2006) showed that GPX4 associated with
membranes, cytoplasm, and mitochondria, and that GPX4 activity showed an
identical distribution. Western blot analysis detected GPX4 at an
apparent molecular mass of 20 to 21 kD.
Roveri et al. (1992) found that rat Gpx4 was present primarily in
testis. Januel et al. (2006) stated that rat has mitochondrial and
nonmitochondrial forms of Gpx4.
Borchert et al. (2003) characterized the expression of 2 major isoforms
of Gpx4 in mouse tissues. One isoform, which they designated the
phospholipid (phGpx) form, was expressed in many tissues. The other,
designated the sperm nucleus (snGpx) isoform, was detected in mouse
testis and kidney, as well as in a human embryonic kidney cell line.
Subcellular fractionation and immunoelectron microscopy revealed
cytosolic localization. Immunohistochemical staining of mouse kidneys
showed staining for snGpx in cortical and medullary interstitial cells.
Analysis of the 5-prime flanking region common to both isoforms revealed
strong promoter activity. The snGpx4 promoter, which contains 334 bp of
intronic sequence, suppressed the activity of the common promoter.
GENE FUNCTION
In human umbilical vein endothelial cells (HUVECs), Sneddon et al.
(2003) observed a dose-dependent increase in GPX4 mRNA and protein
levels with increasing Se concentration until the Se concentration
reached 76 nM. GPX4 enzyme activity was optimum at an even higher Se
concentration. Sneddon et al. (2003) noted that these findings
contrasted with findings in other tissues and cell types, suggesting
that Se regulates GPX4 in a tissue- and cell-type specific manner,
possibly reflecting the relative importance of GPX4 in individual
tissues. They also found that, in addition to Se, fatty acids,
cytokines, and redox state regulated GPX4 expression and activity, but
sometimes in different and opposing ways.
Activation of platelets by agonists such as thrombin (F2; 176930) leads
to a dramatic increase in cell surface expression of several receptors,
as well as changes in platelet shape, release of arachidonic acid from
phospholipids, and increased level of peroxides. Using fractionated
human platelets and confocal immunofluorescence microscopy, Januel et
al. (2006) found that GPX4 protein and enzymatic activity redistributed
from the cytosol to membranes following platelet activation. They
hypothesized that mobilization of GPX4 toward membranes protects
platelets against the burst of lipid hydroperoxides and limits the stage
of activation.
By yeast 3-hybrid screening of a mouse testis cDNA library, followed by
RNA mobility gel shift assays, Ufer et al. (2008) found that the
RNA-binding protein Grsf1 (604851) bound an AGGGGA motif in the 5-prime
UTR of mitochondrial Gpx4. Grsf1 upregulated Gpx4 UTR-dependent reporter
gene expression, recruited mitochondrial Gpx4 mRNA to translationally
active polysomes, and coimmunoprecipitated with Gpx4 mRNA. During
embryonic mouse brain development, Grsf1 and mitochondrial Gpx4 were
coexpressed, and knockdown of Grsf1 via small interfering RNA prevented
embryonic Gpx4 expression. Compared with mock controls, Grsf1-knockdown
embryos showed developmental retardation that paralleled increased
apoptosis and massive lipid peroxidation. Overexpression of
mitochondrial Gpx4 prevented the apoptotic changes and rescued
development in Grsf1-knockdown embryos. Ufer et al. (2008) concluded
that GRSF1 upregulates translation of GPX4 mRNA and that both proteins
are required for embryonic brain development.
BIOCHEMICAL FEATURES
To overcome inefficient selenocysteine-incorporating machinery in
recombinant systems, Scheerer et al. (2007) expressed recombinant human
cytosolic GPX4 containing a sec46-to-cys (U46C) mutation, which retains
residual catalytic activity, in E. coli. They solved the crystal
structure of this molecule to 1.55-angstrom resolution. X-ray data
indicated that the monomeric protein consisted of 4 alpha helices and 7
beta strands. The catalytic triad (cys46, gln81, and trp136) localized
at a flat impression on the protein surface extending into a
surface-exposed patch of basic amino acids (lys48, lys135, and arg152)
that also contained polar thr139. Mutation analysis confirmed the
functional importance of the catalytic triad. Like the wildtype enzyme,
the U46C mutant exhibited a strong tendency toward polymerization, which
was prevented by reductants. Site-directed mutagenesis suggested
involvement of the catalytic cys46 and surface-exposed cys10 and cys66
in polymer formation. In GPX4 crystals, these residues contacted
adjacent protein monomers.
GENE STRUCTURE
Kelner and Montoya (1998) determined that the human GPX4 gene spans 2.8
kb and contains 7 exons. Analysis of the gene sequence identified a
potential alternative tissue-specific first exon.
MAPPING
By Southern analysis of genomic DNA from human/hamster somatic cell
hybrids, Chu (1994) showed that the GPX4 gene is located on chromosome
19. By fluorescence in situ hybridization, Kelner and Montoya (1998)
assigned the gene to chromosome 19p13.3.
MOLECULAR GENETICS
Villette et al. (2002) examined the 3-prime UTR of the GPX4 gene in 66
healthy Scottish volunteers and identified a T-C SNP at position 718,
near the predicted SECIS element. The distribution of this SNP was in
Hardy-Weinberg equilibrium, with 34% CC homozygotes, 25% TT homozygotes,
and 41% TC heterozygotes. Individuals of different genotypes exhibited
significant differences in the levels of lymphocyte 5-lipoxygenase total
products, with CC homozygotes showing 36% and 44% more products than TT
homozygotes and TC heterozygotes, respectively. Villette et al. (2002)
concluded that GPX4 has a regulatory role in leukotriene biosynthesis
and that the 718T-C SNP has functional effects.
ANIMAL MODEL
Ran et al. (2004) stated that Gpx4 deletion in mice is embryonic lethal,
and that embryonic fibroblasts from Gpx4 +/- mice exhibit increased
lipid peroxidation, more cell death after exposure to oxidizing agents,
and growth retardation under high oxygen levels. They found that
expression of human GPX4 rescued the lethal phenotype of Gpx4 -/- mice.
Transgenic mice overexpressing human GPX4 showed reduced oxidative
injury after oxidative stress.
*FIELD* RF
1. Borchert, A.; Savaskan, N. E.; Kuhn, H.: Regulation of expression
of the phospholipid hydroperoxide/sperm nucleus glutathione peroxidase
gene: tissue-specific expression pattern and identification of functional
cis- and trans-regulatory elements. J. Biol. Chem. 278: 2571-2580,
2003.
2. Chu, F.-F.: The human glutathione peroxidase genes GPX2, GPX3,
and GPX4 map to chromosomes 14, 5, and 19, respectively. Cytogenet.
Cell Genet. 66: 96-98, 1994.
3. Esworthy, R. S.; Doan, K.; Doroshow, J. H.; Chu, F.-F.: Cloning
and sequencing of the cDNA encoding a human testis phospholipid hydroperoxide
glutathione peroxidase. Gene 144: 317-318, 1994.
4. Januel, C.; El Hentati, F.-Z.; Carreras, M.; Arthur, J. R.; Calzada,
C.; Lagarde, M.; Vericel, E.: Phospholipid-hydroperoxide glutathione
peroxidase (GPx-4) localization in resting platelets, and compartmental
change during platelet activation. Biochim. Biophys. Acta 1761:
1228-1234, 2006.
5. Kelner, M. J.; Montoya, M. A.: Structural organization of the
human selenium-dependent phospholipid hydroperoxide glutathione peroxidase
gene (GPX4): chromosomal localization to 19p13.3. Biochem. Biophys.
Res. Commun. 249: 53-55, 1998.
6. Ran, Q.; Liang, H.; Gu, M.; Qi, W.; Walter, C. A.; Roberts, L.
J., II; Herman, B.; Richardson, A.; Van Remmen, H.: Transgenic mice
overexpressing glutathione peroxidase 4 are protected against oxidative
stress-induced apoptosis. J. Biol. Chem. 279: 55137-55146, 2004.
7. Roveri, A.; Casasco, A.; Maiorino, M.; Dalan, P.; Calligaro, A.;
Ursini, F.: Phospholipid hydroperoxide glutathione peroxidase of
rat testis. J. Biol. Chem. 267: 6142-6146, 1992.
8. Scheerer, P.; Borchert, A.; Krauss, N.; Wessner, H.; Gerth, C.;
Hohne, W.; Kuhn, H.: Structural basis for catalytic activity and
enzyme polymerization of phospholipid hydroperoxide glutathione peroxidase-4
(GPx4). Biochemistry 46: 9041-9049, 2007.
9. Sneddon, A. A.; Wu, H.-C.; Farquharson, A.; Grant, I.; Arthur,
J. R.; Rotondo, D.; Choe, S.-N.; Wahle, K. W. J.: Regulation of selenoprotein
GPx4 expression and activity in human endothelial cells by fatty acids,
cytokines and antioxidants. Atherosclerosis 171: 57-65, 2003.
10. Ufer, C.; Wang, C. C.; Fahling, M.; Schiebel, H.; Thiele, B. J.;
Billett, E. E.; Kuhn, H.; Brochert, A.: Translational regulation
of glutathione peroxidase 4 expression through guanine-rich sequence-binding
factor 1 is essential for embryonic brain development. Genes Dev. 22:
1838-1850, 2008.
11. Villette, S.; Kyle, J. A. M.; Brown, K. M.; Pickard, K.; Milne,
J. S.; Nicol, F.; Arthur, J. R.; Hesketh, J. E.: A novel single nucleotide
polymorphism in the 3-prime untranslated region of human glutathione
peroxidase 4 influences lipoxygenase metabolism. Blood Cells Molec.
Dis. 29: 174-178, 2002.
*FIELD* CN
Patricia A. Hartz - updated: 8/25/2008
Patricia A. Hartz - updated: 3/10/2003
Carol A. Bocchini - updated: 10/20/1998
*FIELD* CD
Victor A. McKusick: 4/20/1994
*FIELD* ED
carol: 01/04/2011
carol: 2/2/2009
mgross: 8/26/2008
terry: 8/25/2008
mgross: 3/12/2003
terry: 3/10/2003
dkim: 10/21/1998
carol: 10/20/1998
dkim: 7/2/1998
carol: 4/20/1994
*RECORD*
*FIELD* NO
138322
*FIELD* TI
*138322 GLUTATHIONE PEROXIDASE 4; GPX4
;;PHOSPHOLIPID HYDROPEROXIDE GLUTATHIONE PEROXIDASE; PHGPX
read more*FIELD* TX
DESCRIPTION
GPX4 reduces phospholipid hydroperoxides within membranes and
lipoproteins and acts in conjunction with alpha-tocopherol to inhibit
lipid peroxidation. Lipid peroxidation is implicated in a number of
pathophysiologic processes, including inflammation and atherogenesis.
GPX4 is a selenoprotein whose production and activity are sensitive to
selenium (Se), which is incorporated into selenoproteins as
selenocysteine (summary by Sneddon et al., 2003).
CLONING
Using porcine Phgpx to screen a testis cDNA library, Esworthy et al.
(1994) cloned human GPX4, which they called PHGPX. The 3-prime UTR
contains a selenocysteine insertion sequence (SECIS) required for
insertion of selenocysteine at an opal codon (UGA). The deduced
197-amino acid protein has a calculated molecular mass of 19 kD. It has
putative active-site tryptophan and glutamic acid residues that are
predicted to interact with selenocysteine, and a tyrosine residue that
is phosphorylated in the porcine protein.
By fractionation and immunofluorescence microscopy of resting human
platelets, Januel et al. (2006) showed that GPX4 associated with
membranes, cytoplasm, and mitochondria, and that GPX4 activity showed an
identical distribution. Western blot analysis detected GPX4 at an
apparent molecular mass of 20 to 21 kD.
Roveri et al. (1992) found that rat Gpx4 was present primarily in
testis. Januel et al. (2006) stated that rat has mitochondrial and
nonmitochondrial forms of Gpx4.
Borchert et al. (2003) characterized the expression of 2 major isoforms
of Gpx4 in mouse tissues. One isoform, which they designated the
phospholipid (phGpx) form, was expressed in many tissues. The other,
designated the sperm nucleus (snGpx) isoform, was detected in mouse
testis and kidney, as well as in a human embryonic kidney cell line.
Subcellular fractionation and immunoelectron microscopy revealed
cytosolic localization. Immunohistochemical staining of mouse kidneys
showed staining for snGpx in cortical and medullary interstitial cells.
Analysis of the 5-prime flanking region common to both isoforms revealed
strong promoter activity. The snGpx4 promoter, which contains 334 bp of
intronic sequence, suppressed the activity of the common promoter.
GENE FUNCTION
In human umbilical vein endothelial cells (HUVECs), Sneddon et al.
(2003) observed a dose-dependent increase in GPX4 mRNA and protein
levels with increasing Se concentration until the Se concentration
reached 76 nM. GPX4 enzyme activity was optimum at an even higher Se
concentration. Sneddon et al. (2003) noted that these findings
contrasted with findings in other tissues and cell types, suggesting
that Se regulates GPX4 in a tissue- and cell-type specific manner,
possibly reflecting the relative importance of GPX4 in individual
tissues. They also found that, in addition to Se, fatty acids,
cytokines, and redox state regulated GPX4 expression and activity, but
sometimes in different and opposing ways.
Activation of platelets by agonists such as thrombin (F2; 176930) leads
to a dramatic increase in cell surface expression of several receptors,
as well as changes in platelet shape, release of arachidonic acid from
phospholipids, and increased level of peroxides. Using fractionated
human platelets and confocal immunofluorescence microscopy, Januel et
al. (2006) found that GPX4 protein and enzymatic activity redistributed
from the cytosol to membranes following platelet activation. They
hypothesized that mobilization of GPX4 toward membranes protects
platelets against the burst of lipid hydroperoxides and limits the stage
of activation.
By yeast 3-hybrid screening of a mouse testis cDNA library, followed by
RNA mobility gel shift assays, Ufer et al. (2008) found that the
RNA-binding protein Grsf1 (604851) bound an AGGGGA motif in the 5-prime
UTR of mitochondrial Gpx4. Grsf1 upregulated Gpx4 UTR-dependent reporter
gene expression, recruited mitochondrial Gpx4 mRNA to translationally
active polysomes, and coimmunoprecipitated with Gpx4 mRNA. During
embryonic mouse brain development, Grsf1 and mitochondrial Gpx4 were
coexpressed, and knockdown of Grsf1 via small interfering RNA prevented
embryonic Gpx4 expression. Compared with mock controls, Grsf1-knockdown
embryos showed developmental retardation that paralleled increased
apoptosis and massive lipid peroxidation. Overexpression of
mitochondrial Gpx4 prevented the apoptotic changes and rescued
development in Grsf1-knockdown embryos. Ufer et al. (2008) concluded
that GRSF1 upregulates translation of GPX4 mRNA and that both proteins
are required for embryonic brain development.
BIOCHEMICAL FEATURES
To overcome inefficient selenocysteine-incorporating machinery in
recombinant systems, Scheerer et al. (2007) expressed recombinant human
cytosolic GPX4 containing a sec46-to-cys (U46C) mutation, which retains
residual catalytic activity, in E. coli. They solved the crystal
structure of this molecule to 1.55-angstrom resolution. X-ray data
indicated that the monomeric protein consisted of 4 alpha helices and 7
beta strands. The catalytic triad (cys46, gln81, and trp136) localized
at a flat impression on the protein surface extending into a
surface-exposed patch of basic amino acids (lys48, lys135, and arg152)
that also contained polar thr139. Mutation analysis confirmed the
functional importance of the catalytic triad. Like the wildtype enzyme,
the U46C mutant exhibited a strong tendency toward polymerization, which
was prevented by reductants. Site-directed mutagenesis suggested
involvement of the catalytic cys46 and surface-exposed cys10 and cys66
in polymer formation. In GPX4 crystals, these residues contacted
adjacent protein monomers.
GENE STRUCTURE
Kelner and Montoya (1998) determined that the human GPX4 gene spans 2.8
kb and contains 7 exons. Analysis of the gene sequence identified a
potential alternative tissue-specific first exon.
MAPPING
By Southern analysis of genomic DNA from human/hamster somatic cell
hybrids, Chu (1994) showed that the GPX4 gene is located on chromosome
19. By fluorescence in situ hybridization, Kelner and Montoya (1998)
assigned the gene to chromosome 19p13.3.
MOLECULAR GENETICS
Villette et al. (2002) examined the 3-prime UTR of the GPX4 gene in 66
healthy Scottish volunteers and identified a T-C SNP at position 718,
near the predicted SECIS element. The distribution of this SNP was in
Hardy-Weinberg equilibrium, with 34% CC homozygotes, 25% TT homozygotes,
and 41% TC heterozygotes. Individuals of different genotypes exhibited
significant differences in the levels of lymphocyte 5-lipoxygenase total
products, with CC homozygotes showing 36% and 44% more products than TT
homozygotes and TC heterozygotes, respectively. Villette et al. (2002)
concluded that GPX4 has a regulatory role in leukotriene biosynthesis
and that the 718T-C SNP has functional effects.
ANIMAL MODEL
Ran et al. (2004) stated that Gpx4 deletion in mice is embryonic lethal,
and that embryonic fibroblasts from Gpx4 +/- mice exhibit increased
lipid peroxidation, more cell death after exposure to oxidizing agents,
and growth retardation under high oxygen levels. They found that
expression of human GPX4 rescued the lethal phenotype of Gpx4 -/- mice.
Transgenic mice overexpressing human GPX4 showed reduced oxidative
injury after oxidative stress.
*FIELD* RF
1. Borchert, A.; Savaskan, N. E.; Kuhn, H.: Regulation of expression
of the phospholipid hydroperoxide/sperm nucleus glutathione peroxidase
gene: tissue-specific expression pattern and identification of functional
cis- and trans-regulatory elements. J. Biol. Chem. 278: 2571-2580,
2003.
2. Chu, F.-F.: The human glutathione peroxidase genes GPX2, GPX3,
and GPX4 map to chromosomes 14, 5, and 19, respectively. Cytogenet.
Cell Genet. 66: 96-98, 1994.
3. Esworthy, R. S.; Doan, K.; Doroshow, J. H.; Chu, F.-F.: Cloning
and sequencing of the cDNA encoding a human testis phospholipid hydroperoxide
glutathione peroxidase. Gene 144: 317-318, 1994.
4. Januel, C.; El Hentati, F.-Z.; Carreras, M.; Arthur, J. R.; Calzada,
C.; Lagarde, M.; Vericel, E.: Phospholipid-hydroperoxide glutathione
peroxidase (GPx-4) localization in resting platelets, and compartmental
change during platelet activation. Biochim. Biophys. Acta 1761:
1228-1234, 2006.
5. Kelner, M. J.; Montoya, M. A.: Structural organization of the
human selenium-dependent phospholipid hydroperoxide glutathione peroxidase
gene (GPX4): chromosomal localization to 19p13.3. Biochem. Biophys.
Res. Commun. 249: 53-55, 1998.
6. Ran, Q.; Liang, H.; Gu, M.; Qi, W.; Walter, C. A.; Roberts, L.
J., II; Herman, B.; Richardson, A.; Van Remmen, H.: Transgenic mice
overexpressing glutathione peroxidase 4 are protected against oxidative
stress-induced apoptosis. J. Biol. Chem. 279: 55137-55146, 2004.
7. Roveri, A.; Casasco, A.; Maiorino, M.; Dalan, P.; Calligaro, A.;
Ursini, F.: Phospholipid hydroperoxide glutathione peroxidase of
rat testis. J. Biol. Chem. 267: 6142-6146, 1992.
8. Scheerer, P.; Borchert, A.; Krauss, N.; Wessner, H.; Gerth, C.;
Hohne, W.; Kuhn, H.: Structural basis for catalytic activity and
enzyme polymerization of phospholipid hydroperoxide glutathione peroxidase-4
(GPx4). Biochemistry 46: 9041-9049, 2007.
9. Sneddon, A. A.; Wu, H.-C.; Farquharson, A.; Grant, I.; Arthur,
J. R.; Rotondo, D.; Choe, S.-N.; Wahle, K. W. J.: Regulation of selenoprotein
GPx4 expression and activity in human endothelial cells by fatty acids,
cytokines and antioxidants. Atherosclerosis 171: 57-65, 2003.
10. Ufer, C.; Wang, C. C.; Fahling, M.; Schiebel, H.; Thiele, B. J.;
Billett, E. E.; Kuhn, H.; Brochert, A.: Translational regulation
of glutathione peroxidase 4 expression through guanine-rich sequence-binding
factor 1 is essential for embryonic brain development. Genes Dev. 22:
1838-1850, 2008.
11. Villette, S.; Kyle, J. A. M.; Brown, K. M.; Pickard, K.; Milne,
J. S.; Nicol, F.; Arthur, J. R.; Hesketh, J. E.: A novel single nucleotide
polymorphism in the 3-prime untranslated region of human glutathione
peroxidase 4 influences lipoxygenase metabolism. Blood Cells Molec.
Dis. 29: 174-178, 2002.
*FIELD* CN
Patricia A. Hartz - updated: 8/25/2008
Patricia A. Hartz - updated: 3/10/2003
Carol A. Bocchini - updated: 10/20/1998
*FIELD* CD
Victor A. McKusick: 4/20/1994
*FIELD* ED
carol: 01/04/2011
carol: 2/2/2009
mgross: 8/26/2008
terry: 8/25/2008
mgross: 3/12/2003
terry: 3/10/2003
dkim: 10/21/1998
carol: 10/20/1998
dkim: 7/2/1998
carol: 4/20/1994