ID GPX1_HUMAN Reviewed; 203 AA. AC P07203; Q7Z5H1; Q9BW12; DT 01-APR-1988, integrated into UniProtKB/Swiss-Prot. DT 02-NOV-2010, sequence version 4. DT 25-JAN-2012, entry version 144. DE RecName: Full=Glutathione peroxidase 1; DE Short=GPx-1; DE Short=GSHPx-1; DE EC=1.11.1.9; 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], AND VARIANT 7-ALA-ALA-8 DEL. 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], AND VARIANT 7-ALA-ALA-8 DEL. 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], AND VARIANT 7-ALA-ALA-8 DEL. 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], AND VARIANT 7-ALA-ALA-8 DEL. 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-8 DEL. 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; THR-194 AND RP LEU-200. RG NIEHS SNPs program; RL Submitted (JUN-2003) to the EMBL/GenBank/DDBJ databases. RN [7] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=16641997; DOI=10.1038/nature04728; RA Muzny D.M., Scherer S.E., Kaul R., Wang J., Yu J., Sudbrak R., RA Buhay C.J., Chen R., Cree A., Ding Y., Dugan-Rocha S., Gill R., RA Gunaratne P., Harris R.A., Hawes A.C., Hernandez J., Hodgson A.V., RA Hume J., Jackson A., Khan Z.M., Kovar-Smith C., Lewis L.R., RA Lozado R.J., Metzker M.L., Milosavljevic A., Miner G.R., Morgan M.B., RA Nazareth L.V., Scott G., Sodergren E., Song X.-Z., Steffen D., Wei S., RA Wheeler D.A., Wright M.W., Worley K.C., Yuan Y., Zhang Z., Adams C.Q., RA Ansari-Lari M.A., Ayele M., Brown M.J., Chen G., Chen Z., RA Clendenning J., Clerc-Blankenburg K.P., Chen R., Chen Z., Davis C., RA Delgado O., Dinh H.H., Dong W., Draper H., Ernst S., Fu G., RA Gonzalez-Garay M.L., Garcia D.K., Gillett W., Gu J., Hao B., RA Haugen E., Havlak P., He X., Hennig S., Hu S., Huang W., Jackson L.R., RA Jacob L.S., Kelly S.H., Kube M., Levy R., Li Z., Liu B., Liu J., RA Liu W., Lu J., Maheshwari M., Nguyen B.-V., Okwuonu G.O., Palmeiri A., RA Pasternak S., Perez L.M., Phelps K.A., Plopper F.J., Qiang B., RA Raymond C., Rodriguez R., Saenphimmachak C., Santibanez J., Shen H., RA Shen Y., Subramanian S., Tabor P.E., Verduzco D., Waldron L., Wang J., RA Wang J., Wang Q., Williams G.A., Wong G.K.-S., Yao Z., Zhang J., RA Zhang X., Zhao G., Zhou J., Zhou Y., Nelson D., Lehrach H., RA Reinhardt R., Naylor S.L., Yang H., Olson M., Weinstock G., RA Gibbs R.A.; RT "The DNA sequence, annotation and analysis of human chromosome 3."; RL Nature 440:1194-1198(2006). RN [8] 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 [9] 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 [10] RP X-RAY CRYSTALLOGRAPHY (1.5 ANGSTROMS) OF 14-198. RG Structural genomics consortium (SGC); RT "Crystal structure of the selenocysteine to glycine mutant of human RT glutathione peroxidase 1."; RL Submitted (FEB-2009) to the PDB data bank. RN [11] RP VARIANT LEU-200. 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 [12] RP VARIANTS ALA-8 DEL AND 7-ALA-ALA-8 DEL. 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 [13] RP VARIANTS ALA-8 DEL AND LEU-200. 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 [14] RP VARIANT LEU-200. 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. Interacts with MIEN1. 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; AC121247; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; BC000742; AAH00742.3; -; mRNA. DR IPI; IPI00927606; -. DR PIR; A42152; OPHUE. DR RefSeq; NP_000572.2; NM_000581.2. DR RefSeq; NP_958799.1; NM_201397.1. DR UniGene; Hs.76686; -. DR PDB; 2F8A; X-ray; 1.50 A; A/B=14-196. DR PDBsum; 2F8A; -. DR ProteinModelPortal; P07203; -. DR SMR; P07203; 14-197. DR STRING; P07203; -. DR PeroxiBase; 3600; HsGPx01-a. DR PhosphoSite; P07203; -. DR DMDM; 311033481; -. DR SWISS-2DPAGE; P07203; -. DR OGP; P07203; -. DR PRIDE; P07203; -. DR Ensembl; ENST00000419783; ENSP00000407375; ENSG00000233276. DR GeneID; 2876; -. DR KEGG; hsa:2876; -. DR CTD; 2876; -. DR GeneCards; GC03M049369; -. DR H-InvDB; HIX0003298; -. DR HGNC; HGNC:4553; GPX1. DR HPA; CAB011582; -. DR MIM; 138320; gene+phenotype. DR neXtProt; NX_P07203; -. DR PharmGKB; PA28949; -. DR eggNOG; prNOG12554; -. DR HOGENOM; HBG648990; -. DR HOVERGEN; HBG004333; -. DR InParanoid; P07203; -. DR OMA; CRNDISW; -. DR OrthoDB; EOG4SBF08; -. DR PhylomeDB; P07203; -. DR BioCyc; MetaCyc:MONOMER-9882; -. DR Reactome; REACT_111217; Metabolism. DR DrugBank; DB00143; Glutathione. DR NextBio; 11353; -. DR Bgee; P07203; -. DR CleanEx; HS_GPX1; -. DR Genevestigator; P07203; -. DR GermOnline; ENSG00000211447; Homo sapiens. DR GO; GO:0005829; C:cytosol; TAS:Reactome. DR GO; GO:0005739; C:mitochondrion; IDA:BHF-UCL. DR GO; GO:0004866; F:endopeptidase inhibitor activity; IDA:BHF-UCL. DR GO; GO:0004602; F:glutathione peroxidase activity; IDA:BHF-UCL. DR GO; GO:0017124; F:SH3 domain binding; IPI:BHF-UCL. DR GO; GO:0006916; P:anti-apoptosis; IMP:BHF-UCL. DR GO; GO:0045454; P:cell redox homeostasis; IDA:BHF-UCL. DR GO; GO:0006749; P:glutathione metabolic process; IDA:BHF-UCL. DR GO; GO:0060047; P:heart contraction; IMP:BHF-UCL. DR GO; GO:0042744; P:hydrogen peroxide catabolic process; IDA:BHF-UCL. DR GO; GO:0043154; P:negative regulation of cysteine-type endopeptidase activity involved in apoptotic process; IMP:BHF-UCL. DR GO; GO:0006144; P:purine base metabolic process; TAS:Reactome. DR GO; GO:0006195; P:purine nucleotide catabolic process; TAS:Reactome. DR GO; GO:0040029; P:regulation of gene expression, epigenetic; IDA:BHF-UCL. DR GO; GO:0033599; P:regulation of mammary gland epithelial cell proliferation; IMP:BHF-UCL. DR GO; GO:0061136; P:regulation of proteasomal protein catabolic process; IDA:BHF-UCL. DR GO; GO:0001836; P:release of cytochrome c from mitochondria; IMP:BHF-UCL. DR GO; GO:0010269; P:response to selenium ion; IMP:BHF-UCL. DR GO; GO:0009650; P:UV protection; IMP:BHF-UCL. DR InterPro; IPR000889; Glutathione_peroxidase. DR InterPro; IPR012336; Thioredoxin-like_fold. DR Gene3D; G3DSA:3.40.30.10; Thioredoxin_fold; 1. DR KO; K00432; -. DR PANTHER; PTHR11592; Glut_peroxidase; 1. DR Pfam; PF00255; GSHPx; 1. DR PIRSF; PIRSF000303; Glutathion_perox; 1. DR PRINTS; PR01011; GLUTPROXDASE. DR SUPFAM; SSF52833; Thiordxn-like_fd; 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; Acetylation; Complete proteome; Cytoplasm; KW Oxidoreductase; Peroxidase; Polymorphism; Reference proteome; KW Selenocysteine. FT CHAIN 1 203 Glutathione peroxidase 1. FT /FTId=PRO_0000066610. FT ACT_SITE 49 49 FT NON_STD 49 49 Selenocysteine. FT MOD_RES 148 148 N6-acetyllysine (By similarity). FT VARIANT 5 5 R -> P (in dbSNP:rs8179169). FT /FTId=VAR_020912. FT VARIANT 7 8 Missing. FT /FTId=VAR_020913. FT VARIANT 8 8 Missing. FT /FTId=VAR_020914. FT VARIANT 194 194 A -> T. FT /FTId=VAR_020915. FT VARIANT 200 200 P -> L (in 30% of the population; FT associated with an increased risk of FT cancer; dbSNP:rs1050450). FT /FTId=VAR_007904. FT CONFLICT 93 93 L -> Q (in Ref. 3; CAA31992). FT HELIX 16 18 FT STRAND 40 45 FT HELIX 52 65 FT STRAND 72 74 FT HELIX 89 91 FT HELIX 92 98 FT HELIX 124 132 FT HELIX 147 149 FT STRAND 152 154 FT STRAND 166 169 FT STRAND 177 179 FT HELIX 185 188 FT HELIX 189 196 SQ SEQUENCE 203 AA; 22088 MW; 5DB11579C66FE8E5 CRC64; MCAARLAAAA AAAQSVYAFS ARPLAGGEPV SLGSLRGKVL LIENVASLUG TTVRDYTQMN ELQRRLGPRG LVVLGFPCNQ FGHQENAKNE EILNSLKYVR PGGGFEPNFM LFEKCEVNGA GAHPLFAFLR EALPAPSDDA TALMTDPKLI TWSPVCRNDV AWNFEKFLVG PDGVPLRRYS RRFQTIDIEP DIEALLSQGP SCA //