ID GPX4_HUMAN Reviewed; 197 AA. AC P36969; O43381; Q6PJ59; Q9UPK2; DT 01-JUN-1994, integrated into UniProtKB/Swiss-Prot. DT 26-FEB-2008, sequence version 3. DT 25-NOV-2008, entry version 91. 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 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 MEDLINE=94314239; 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 MEDLINE=98381025; 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. RA Rieder M.J., Livingston R.J., Daniels M.R., Chung M.-W., RA Miyamoto K.E., Nguyen C.P., Nguyen D.A., Poel C.L., Robertson P.D., RA Schackwitz W.S., Sherwood J.K., Witrak L.A., Nickerson D.A.; RT "NIEHS-SNPs, environmental genome project, NIEHS ES15478, Department RT of Genome Sciences, Seattle, WA (URL: http://egp.gs.washington.edu)."; 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 VARIANT INFERTILITY THR-120, AND VARIANT ASN-2. RX MEDLINE=22535270; 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: 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 -!- SUBCELLULAR LOCATION: Mitochondrion. 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 -!- DISEASE: Defects in GPX4 may be a cause of infertility. CC -!- SIMILARITY: Belongs to the glutathione peroxidase family. 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; -. DR RefSeq; NP_001034937.1; -. DR RefSeq; NP_002076.2; -. 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 PeroxiBase; 3603; HsGPx04-a. DR PeroxiBase; 3632; HsGPx04-b. DR PeroxiBase; 3633; HsGPx04-c. DR REPRODUCTION-2DPAGE; IPI00304814; -. DR Ensembl; ENSG00000167468; Homo sapiens. DR GeneID; 2879; -. DR KEGG; hsa:2879; -. DR HGNC; HGNC:4556; GPX4. DR HPA; CAB008630; -. DR MIM; 138322; gene. DR PharmGKB; PA28952; -. DR HOGENOM; P36969; -. DR HOVERGEN; P36969; -. DR BioCyc; MetaCyc:MON-9881; -. DR DrugBank; DB00143; Glutathione. DR NextBio; 11367; -. DR CleanEx; HS_GPX4; -. DR GermOnline; ENSG00000167468; Homo sapiens. DR GO; GO:0004602; F:glutathione peroxidase activity; TAS:UniProtKB. DR GO; GO:0047066; F:phospholipid-hydroperoxide glutathione pero...; IEA:EC. DR GO; GO:0008430; F:selenium binding; IEA:UniProtKB-KW. DR GO; GO:0007275; P:multicellular organismal development; IEA:UniProtKB-KW. DR GO; GO:0055114; P:oxidation reduction; TAS:UniProtKB. DR GO; GO:0006644; P:phospholipid metabolic process; TAS:UniProtKB. DR GO; GO:0006979; P:response to oxidative stress; IEA:InterPro. DR InterPro; IPR000889; Glut_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 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; Cytoplasm; KW Developmental protein; Disease mutation; Mitochondrion; KW Oxidoreductase; Peroxidase; Polymorphism; Selenium; Selenocysteine; KW 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. FT /FTId=VAR_017063. FT VARIANT 120 120 A -> T (in infertility; reduced FT activity). FT /FTId=VAR_017064. FT HELIX 41 43 FT STRAND 44 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 113 122 FT STRAND 127 130 FT STRAND 134 137 FT HELIX 142 147 FT HELIX 151 153 FT STRAND 156 160 FT STRAND 167 170 FT STRAND 176 180 FT HELIX 186 192 FT HELIX 193 196 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 //