ID GPX1_HUMAN Reviewed; 201 AA. AC P07203; Q7Z5H1; Q9BW12; DT 01-APR-1988, integrated into UniProtKB/Swiss-Prot. DT 26-FEB-2008, sequence version 3. DT 03-MAR-2009, entry version 113. DE RecName: Full=Glutathione peroxidase 1; DE EC=1.11.1.9; DE AltName: Full=GSHPx-1; DE Short=GPx-1; DE AltName: Full=Cellular glutathione peroxidase; GN Name=GPX1; 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]. RX MEDLINE=88015555; PubMed=3658677; DOI=10.1093/nar/15.17.7178; RA Sukenaga Y., Ishida K., Takeda T., Takagi K.; RT "cDNA sequence coding for human glutathione peroxidase."; RL Nucleic Acids Res. 15:7178-7178(1987). RN [2] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RX MEDLINE=88096498; PubMed=3697069; DOI=10.1093/nar/15.23.10051; RA Ishida K., Morino T., Takagi K., Sukenaga Y.; RT "Nucleotide sequence of a human gene for glutathione peroxidase."; RL Nucleic Acids Res. 15:10051-10051(1987). RN [3] RP NUCLEOTIDE SEQUENCE [MRNA]. RC TISSUE=Kidney; RX MEDLINE=87260018; PubMed=2955287; DOI=10.1093/nar/15.13.5484; RA Mullenbach G.T., Tabrizi A., Irvine B.D., Bell G.I., Hallewell R.A.; RT "Sequence of a cDNA coding for human glutathione peroxidase confirms RT TGA encodes active site selenocysteine."; RL Nucleic Acids Res. 15:5484-5484(1987). RN [4] RP NUCLEOTIDE SEQUENCE [MRNA]. RX MEDLINE=90169985; PubMed=2307470; DOI=10.1016/0888-7543(90)90566-D; RA Chada S., le Beau M.M., Casey L., Newburger P.E.; RT "Isolation and chromosomal localization of the human glutathione RT peroxidase gene."; RL Genomics 6:268-271(1990). RN [5] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANT ALA-11 INS. RX MEDLINE=92210561; PubMed=1556108; RA Moscow J.A., Morrow C.S., He R., Mullenbach G.T., Cowan K.H.; RT "Structure and function of the 5'-flanking sequence of the human RT cytosolic selenium-dependent glutathione peroxidase gene (hgpx1)."; RL J. Biol. Chem. 267:5949-5958(1992). RN [6] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS PRO-5; ALA-ALA-11 INS; RP THR-192 AND LEU-198. RG NIEHS SNPs program; RL Submitted (JUN-2003) to the EMBL/GenBank/DDBJ databases. RN [7] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Placenta; 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 [8] RP IDENTIFICATION BY MASS SPECTROMETRY. RA Colinge J., Superti-Furga G., Bennett K.L.; RL Submitted (OCT-2008) to UniProtKB. RN [9] RP VARIANT LEU-198. RX MEDLINE=99235549; PubMed=10220143; RX DOI=10.1002/(SICI)1098-1004(1999)13:4<294::AID-HUMU6>3.0.CO;2-5; RA Forsberg L., de Faire U., Morgenstern R.; RT "Low yield of polymorphisms from EST blast searching: analysis of RT genes related to oxidative stress and verification of the P197L RT polymorphism in GPX1."; RL Hum. Mutat. 13:294-300(1999). RN [10] RP VARIANTS ALA-11 INS AND ALA-ALA-11 INS. RX MEDLINE=22385359; PubMed=12496980; DOI=10.1038/sj.pcan.4500569; RA Kote-Jarai Z., Durocher F., Edwards S.M., Hamoudi R., Jackson R.A., RA Ardern-Jones A., Murkin A., Dearnaley D.P., Kirby R., Houlston R., RA Easton D.F., Eeles R.; RT "Association between the GCG polymorphism of the selenium dependent RT GPX1 gene and the risk of young onset prostate cancer."; RL Prostate Cancer Prostatic Dis. 5:189-192(2002). RN [11] RP VARIANTS ALA-11 INS AND LEU-198. RX PubMed=15331559; RA Hamanishi T., Furuta H., Kato H., Doi A., Tamai M., Shimomura H., RA Sakagashira S., Nishi M., Sasaki H., Sanke T., Nanjo K.; RT "Functional variants in the glutathione peroxidase-1 (GPx-1) gene are RT associated with increased intima-media thickness of carotid arteries RT and risk of macrovascular diseases in Japanese type 2 diabetic RT patients."; RL Diabetes 53:2455-2460(2004). RN [12] RP VARIANT LEU-198. RX PubMed=15247771; DOI=10.1097/01.ju.0000130942.40597.9d; RA Ichimura Y., Habuchi T., Tsuchiya N., Wang L., Oyama C., Sato K., RA Nishiyama H., Ogawa O., Kato T.; RT "Increased risk of bladder cancer associated with a glutathione RT peroxidase 1 codon 198 variant."; RL J. Urol. 172:728-732(2004). CC -!- FUNCTION: Protects the hemoglobin in erythrocytes from oxidative CC breakdown. CC -!- CATALYTIC ACTIVITY: 2 glutathione + H(2)O(2) = glutathione CC disulfide + 2 H(2)O. CC -!- SUBUNIT: Homotetramer. CC -!- SUBCELLULAR LOCATION: Cytoplasm. CC -!- SIMILARITY: Belongs to the glutathione peroxidase family. CC -!- WEB RESOURCE: Name=NIEHS-SNPs; CC URL="http://egp.gs.washington.edu/data/gpx1/"; CC -!- WEB RESOURCE: Name=Wikipedia; Note=Glutathione peroxidase entry; CC URL="http://en.wikipedia.org/wiki/Glutathione_peroxidase"; 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; Y00433; CAA68491.1; -; mRNA. DR EMBL; Y00483; CAB37833.1; -; Genomic_DNA. DR EMBL; X13709; CAA31992.1; -; mRNA. DR EMBL; X13710; CAA31993.1; -; mRNA. DR EMBL; M21304; AAA75389.2; -; mRNA. DR EMBL; M83094; AAA67540.2; -; Genomic_DNA. DR EMBL; AY327818; AAP80181.1; -; Genomic_DNA. DR EMBL; BC000742; AAH00742.3; -; mRNA. DR IPI; IPI00293975; -. DR PIR; A42152; OPHUE. DR RefSeq; NP_000572.2; -. DR RefSeq; NP_958799.1; -. DR UniGene; Hs.76686; -. DR PDB; 2F8A; X-ray; 1.50 A; A/B=12-196. DR PDBsum; 2F8A; -. DR PeroxiBase; 3600; HsGPx01-a. DR PhosphoSite; P07203; -. DR SWISS-2DPAGE; P07203; -. DR OGP; P07203; -. DR PRIDE; P07203; -. DR Ensembl; ENSG00000197582; Homo sapiens. DR GeneID; 2876; -. DR KEGG; hsa:2876; -. DR KEGG; son:SO_1799; -. DR GeneCards; GC03M049369; -. DR H-InvDB; HIX0003298; -. DR HGNC; HGNC:4553; GPX1. DR MIM; 138320; gene+phenotype. DR Orphanet; 98363; Hemolytic anemia. DR PharmGKB; PA28949; -. DR HOGENOM; P07203; -. DR HOVERGEN; P07203; -. DR BioCyc; MetaCyc:MON-9882; -. DR BRENDA; 1.11.1.9; 247. DR DrugBank; DB00143; Glutathione. DR LinkHub; P07203; -. DR NextBio; 11353; -. DR CleanEx; HS_GPX1; -. DR GermOnline; ENSG00000211447; Homo sapiens. DR GO; GO:0005829; C:cytosol; EXP:Reactome. DR GO; GO:0005739; C:mitochondrion; IDA:UniProtKB. DR GO; GO:0043295; F:glutathione binding; IC:UniProtKB. DR GO; GO:0004602; F:glutathione peroxidase activity; IEA:InterPro. DR GO; GO:0008539; F:proteasome inhibitor activity; IDA:UniProtKB. DR GO; GO:0008430; F:selenium binding; IEA:UniProtKB-KW. DR GO; GO:0017124; F:SH3 domain binding; IPI:UniProtKB. DR GO; GO:0006916; P:anti-apoptosis; IMP:UniProtKB. DR GO; GO:0006749; P:glutathione metabolic process; IDA:UniProtKB. DR GO; GO:0060047; P:heart contraction; IMP:UniProtKB. DR GO; GO:0042744; P:hydrogen peroxide catabolic process; IDA:UniProtKB. DR GO; GO:0043154; P:negative regulation of caspase activity; IMP:UniProtKB. DR GO; GO:0055114; P:oxidation reduction; IEA:UniProtKB-KW. DR GO; GO:0040029; P:regulation of gene expression, epigenetic; IDA:UniProtKB. DR GO; GO:0033599; P:regulation of mammary gland epithelial cell...; IMP:UniProtKB. DR GO; GO:0001836; P:release of cytochrome c from mitochondria; IMP:UniProtKB. DR GO; GO:0010269; P:response to selenium ion; IMP:UniProtKB. DR GO; GO:0009650; P:UV protection; IMP:UniProtKB. 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 3D-structure; Acetylation; Cytoplasm; Oxidoreductase; Peroxidase; KW Polymorphism; Selenium; Selenocysteine. FT CHAIN 1 201 Glutathione peroxidase 1. FT /FTId=PRO_0000066610. FT ACT_SITE 47 47 FT NON_STD 47 47 Selenocysteine. FT MOD_RES 146 146 N6-acetyllysine (By similarity). FT VARIANT 5 5 R -> P. FT /FTId=VAR_020912. FT VARIANT 11 11 A -> AA. FT /FTId=VAR_020913. FT VARIANT 11 11 A -> AAA. FT /FTId=VAR_020914. FT VARIANT 192 192 A -> T. FT /FTId=VAR_020915. FT VARIANT 198 198 P -> L (in 30% of the population; FT associated with an increased risk of FT cancer; dbSNP:rs1050450). FT /FTId=VAR_007904. FT CONFLICT 91 91 L -> Q (in Ref. 3; CAA31992). FT HELIX 14 16 FT HELIX 30 33 FT STRAND 36 43 FT STRAND 45 47 FT HELIX 50 64 FT HELIX 65 67 FT STRAND 69 75 FT TURN 80 83 FT HELIX 87 89 FT HELIX 90 96 FT STRAND 106 110 FT HELIX 122 130 FT STRAND 138 144 FT HELIX 145 147 FT STRAND 150 154 FT STRAND 164 167 FT STRAND 173 177 FT HELIX 183 186 FT HELIX 187 194 SQ SEQUENCE 201 AA; 21946 MW; E84C559299F9811E CRC64; MCAARLAAAA AQSVYAFSAR PLAGGEPVSL GSLRGKVLLI ENVASLUGTT VRDYTQMNEL QRRLGPRGLV VLGFPCNQFG HQENAKNEEI LNSLKYVRPG GGFEPNFMLF EKCEVNGAGA HPLFAFLREA LPAPSDDATA LMTDPKLITW SPVCRNDVAW NFEKFLVGPD GVPLRRYSRR FQTIDIEPDI EALLSQGPSC A //