ID GPX1_MOUSE Reviewed; 201 AA. AC P11352; P12079; Q544W3; Q5RJH8; Q9CR54; DT 01-JUL-1989, integrated into UniProtKB/Swiss-Prot. DT 26-FEB-2008, sequence version 2. DT 27-MAR-2024, entry version 211. DE RecName: Full=Glutathione peroxidase 1 {ECO:0000305}; DE Short=GPx-1; DE Short=GSHPx-1; DE EC=1.11.1.9 {ECO:0000269|PubMed:10754271, ECO:0000269|PubMed:21420488, ECO:0000269|PubMed:36608588, ECO:0000269|PubMed:9126277, ECO:0000269|PubMed:9712879, ECO:0000305|PubMed:9195979}; DE AltName: Full=Cellular glutathione peroxidase; DE AltName: Full=Phospholipid-hydroperoxide glutathione peroxidase GPX1 {ECO:0000303|PubMed:36608588}; DE EC=1.11.1.12 {ECO:0000269|PubMed:36608588, ECO:0000269|PubMed:9195979}; DE AltName: Full=Selenium-dependent glutathione peroxidase 1; GN Name=Gpx1 {ECO:0000312|MGI:MGI:104887}; OS Mus musculus (Mouse). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; OC Murinae; Mus; Mus. OX NCBI_TaxID=10090; RN [1] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND SELENOCYSTEINE AT SEC-47. RC TISSUE=Erythrocyte; RX PubMed=3015592; DOI=10.1002/j.1460-2075.1986.tb04350.x; RA Chambers I., Frampton J., Goldfarb P., Affara N., McBain W., Harrison P.R.; RT "The structure of the mouse glutathione peroxidase gene: the selenocysteine RT in the active site is encoded by the 'termination' codon, TGA."; RL EMBO J. 5:1221-1227(1986). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC STRAIN=C57BL/6J, and NOD; RC TISSUE=Bone marrow, Embryonic liver, Kidney, and Liver; 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., Davis M.J., RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., RA Ringwald M., 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., Sperling S., RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.; RT "The transcriptional landscape of the mammalian genome."; RL Science 309:1559-1563(2005). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC STRAIN=C57BL/6J; TISSUE=Brain; 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 project: RT the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [4] RP PARTIAL NUCLEOTIDE SEQUENCE [MRNA]. RC TISSUE=Liver; RX PubMed=2771650; DOI=10.1093/nar/17.15.6390; RA Dunn D.K., Howells D.D., Richardson J., Goldfarb P.S.; RT "A human cDNA sequence for a novel glutathione peroxidase-related RT selenopeptide, GPRP."; RL Nucleic Acids Res. 17:6390-6390(1989). RN [5] RP FUNCTION, CATALYTIC ACTIVITY, SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY. RX PubMed=9126277; DOI=10.1006/abbi.1997.9901; RA Esworthy R.S., Ho Y.S., Chu F.F.; RT "The Gpx1 gene encodes mitochondrial glutathione peroxidase in the mouse RT liver."; RL Arch. Biochem. Biophys. 340:59-63(1997). RN [6] RP CATALYTIC ACTIVITY, DISRUPTION PHENOTYPE, FUNCTION, AND TISSUE SPECIFICITY. RX PubMed=9195979; DOI=10.1074/jbc.272.26.16644; RA Ho Y.S., Magnenat J.L., Bronson R.T., Cao J., Gargano M., Sugawara M., RA Funk C.D.; RT "Mice deficient in cellular glutathione peroxidase develop normally and RT show no increased sensitivity to hyperoxia."; RL J. Biol. Chem. 272:16644-16651(1997). RN [7] RP FUNCTION, CATALYTIC ACTIVITY, DISRUPTION PHENOTYPE, AND TISSUE SPECIFICITY. RX PubMed=9712879; DOI=10.1074/jbc.273.35.22528; RA de Haan J.B., Bladier C., Griffiths P., Kelner M., O'Shea R.D., RA Cheung N.S., Bronson R.T., Silvestro M.J., Wild S., Zheng S.S., Beart P.M., RA Hertzog P.J., Kola I.; RT "Mice with a homozygous null mutation for the most abundant glutathione RT peroxidase, Gpx1, show increased susceptibility to the oxidative stress- RT inducing agents paraquat and hydrogen peroxide."; RL J. Biol. Chem. 273:22528-22536(1998). RN [8] RP FUNCTION, CATALYTIC ACTIVITY, DISRUPTION PHENOTYPE, AND TISSUE SPECIFICITY. RX PubMed=10754271; DOI=10.1016/s0891-5849(00)00161-1; RA Esposito L.A., Kokoszka J.E., Waymire K.G., Cottrell B., MacGregor G.R., RA Wallace D.C.; RT "Mitochondrial oxidative stress in mice lacking the glutathione peroxidase- RT 1 gene."; RL Free Radic. Biol. Med. 28:754-766(2000). RN [9] RP INTERACTION WITH MIEN1. RX PubMed=17503775; DOI=10.1021/bi602462q; RA Dikiy A., Novoselov S.V., Fomenko D.E., Sengupta A., Carlson B.A., RA Cerny R.L., Ginalski K., Grishin N.V., Hatfield D.L., Gladyshev V.N.; RT "SelT, SelW, SelH, and Rdx12: genomics and molecular insights into the RT functions of selenoproteins of a novel thioredoxin-like family."; RL Biochemistry 46:6871-6882(2007). RN [10] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-7, AND IDENTIFICATION BY MASS RP SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Liver; RX PubMed=17242355; DOI=10.1073/pnas.0609836104; RA Villen J., Beausoleil S.A., Gerber S.A., Gygi S.P.; RT "Large-scale phosphorylation analysis of mouse liver."; RL Proc. Natl. Acad. Sci. U.S.A. 104:1488-1493(2007). RN [11] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Brain, Brown adipose tissue, Heart, Kidney, Liver, Lung, RC Pancreas, Spleen, and Testis; RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001; RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R., RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.; RT "A tissue-specific atlas of mouse protein phosphorylation and expression."; RL Cell 143:1174-1189(2010). RN [12] RP BIOPHYSICOCHEMICAL PROPERTIES, SELENOCYSTEINE AT SEC-47, PARTIAL LOSS OF RP SELENIUM IN ABSENCE OF SOD1, IDENTIFICATION BY MASS SPECTROMETRY, FUNCTION, RP AND CATALYTIC ACTIVITY. RC TISSUE=Liver; RX PubMed=21420488; DOI=10.1016/j.freeradbiomed.2011.03.018; RA Wang S.K., Weaver J.D., Zhang S., Lei X.G.; RT "Knockout of SOD1 promotes conversion of selenocysteine to dehydroalanine RT in murine hepatic GPX1 protein."; RL Free Radic. Biol. Med. 51:197-204(2011). RN [13] RP SUCCINYLATION [LARGE SCALE ANALYSIS] AT LYS-62; LYS-86; LYS-112 AND RP LYS-146, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Liver; RX PubMed=23806337; DOI=10.1016/j.molcel.2013.06.001; RA Park J., Chen Y., Tishkoff D.X., Peng C., Tan M., Dai L., Xie Z., Zhang Y., RA Zwaans B.M., Skinner M.E., Lombard D.B., Zhao Y.; RT "SIRT5-mediated lysine desuccinylation impacts diverse metabolic RT pathways."; RL Mol. Cell 50:919-930(2013). RN [14] RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-62; LYS-86; LYS-112; LYS-119 AND RP LYS-146, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Liver; RX PubMed=23576753; DOI=10.1073/pnas.1302961110; RA Rardin M.J., Newman J.C., Held J.M., Cusack M.P., Sorensen D.J., Li B., RA Schilling B., Mooney S.D., Kahn C.R., Verdin E., Gibson B.W.; RT "Label-free quantitative proteomics of the lysine acetylome in mitochondria RT identifies substrates of SIRT3 in metabolic pathways."; RL Proc. Natl. Acad. Sci. U.S.A. 110:6601-6606(2013). RN [15] RP SELENOCYSTEINE AT SEC-47. RX PubMed=32358195; DOI=10.1073/pnas.2001387117; RA Jedrychowski M.P., Lu G.Z., Szpyt J., Mariotti M., Garrity R., Paulo J.A., RA Schweppe D.K., Laznik-Bogoslavski D., Kazak L., Murphy M.P., RA Gladyshev V.N., Gygi S.P., Chouchani E.T., Spiegelman B.M.; RT "Facultative protein selenation regulates redox sensitivity, adipose tissue RT thermogenesis, and obesity."; RL Proc. Natl. Acad. Sci. U.S.A. 117:10789-10796(2020). RN [16] RP FUNCTION, AND CATALYTIC ACTIVITY. RX PubMed=36608588; DOI=10.1016/j.redox.2022.102593; RA Schwarz M., Loeser A., Cheng Q., Wichmann-Costaganna M., Schaedel P., RA Werz O., Arner E.S., Kipp A.P.; RT "Side-by-side comparison of recombinant human glutathione peroxidases RT identifies overlapping substrate specificities for soluble RT hydroperoxides."; RL Redox Biol. 59:102593-102593(2023). CC -!- FUNCTION: Catalyzes the reduction of hydroperoxides in a glutathione- CC dependent manner thus regulating cellular redox homeostasis CC (PubMed:9126277, PubMed:9195979, PubMed:9712879, PubMed:10754271, CC PubMed:21420488, PubMed:36608588). Can reduce small soluble CC hydroperoxides such as H2O2, cumene hydroperoxide and tert-butyl CC hydroperoxide, as well as several fatty acid-derived hydroperoxides CC (PubMed:9126277, PubMed:9195979, PubMed:9712879, PubMed:10754271, CC PubMed:21420488, PubMed:36608588). In platelets catalyzes the reduction CC of 12-hydroperoxyeicosatetraenoic acid, the primary product of the CC arachidonate 12-lipoxygenase pathway (PubMed:9195979). CC {ECO:0000269|PubMed:10754271, ECO:0000269|PubMed:21420488, CC ECO:0000269|PubMed:36608588, ECO:0000269|PubMed:9126277, CC ECO:0000269|PubMed:9195979, ECO:0000269|PubMed:9712879}. CC -!- CATALYTIC ACTIVITY: CC Reaction=2 glutathione + H2O2 = glutathione disulfide + 2 H2O; CC Xref=Rhea:RHEA:16833, ChEBI:CHEBI:15377, ChEBI:CHEBI:16240, CC ChEBI:CHEBI:57925, ChEBI:CHEBI:58297; EC=1.11.1.9; CC Evidence={ECO:0000269|PubMed:10754271, ECO:0000269|PubMed:21420488, CC ECO:0000269|PubMed:36608588, ECO:0000269|PubMed:9126277, CC ECO:0000269|PubMed:9712879, ECO:0000305|PubMed:9195979}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:16834; CC Evidence={ECO:0000305|PubMed:9195979}; CC -!- CATALYTIC ACTIVITY: CC Reaction=a hydroperoxy polyunsaturated fatty acid + 2 glutathione = a CC hydroxy polyunsaturated fatty acid + glutathione disulfide + H2O; CC Xref=Rhea:RHEA:19057, ChEBI:CHEBI:15377, ChEBI:CHEBI:57925, CC ChEBI:CHEBI:58297, ChEBI:CHEBI:131871, ChEBI:CHEBI:134019; CC EC=1.11.1.12; Evidence={ECO:0000269|PubMed:36608588, CC ECO:0000269|PubMed:9195979}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:19058; CC Evidence={ECO:0000305|PubMed:36608588}; CC -!- CATALYTIC ACTIVITY: CC Reaction=2 glutathione + tert-butyl hydroperoxide = glutathione CC disulfide + H2O + tert-butanol; Xref=Rhea:RHEA:69412, CC ChEBI:CHEBI:15377, ChEBI:CHEBI:45895, ChEBI:CHEBI:57925, CC ChEBI:CHEBI:58297, ChEBI:CHEBI:64090; CC Evidence={ECO:0000269|PubMed:21420488, ECO:0000269|PubMed:9126277}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:69413; CC Evidence={ECO:0000305|PubMed:9126277}; CC -!- CATALYTIC ACTIVITY: CC Reaction=cumene hydroperoxide + 2 glutathione = 2-phenylpropan-2-ol + CC glutathione disulfide + H2O; Xref=Rhea:RHEA:69651, ChEBI:CHEBI:15377, CC ChEBI:CHEBI:57925, ChEBI:CHEBI:58297, ChEBI:CHEBI:78673, CC ChEBI:CHEBI:131607; Evidence={ECO:0000269|PubMed:9126277}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:69652; CC Evidence={ECO:0000305|PubMed:9126277}; CC -!- CATALYTIC ACTIVITY: CC Reaction=(13S)-hydroperoxy-(9Z,11E)-octadecadienoate + 2 glutathione = CC (13S)-hydroxy-(9Z,11E)-octadecadienoate + glutathione disulfide + CC H2O; Xref=Rhea:RHEA:48888, ChEBI:CHEBI:15377, ChEBI:CHEBI:57466, CC ChEBI:CHEBI:57925, ChEBI:CHEBI:58297, ChEBI:CHEBI:90850; CC Evidence={ECO:0000250|UniProtKB:P07203}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:48889; CC Evidence={ECO:0000250|UniProtKB:P07203}; CC -!- CATALYTIC ACTIVITY: CC Reaction=(9S)-hydroperoxy-(10E,12Z)-octadecadienoate + 2 glutathione = CC (9S)-hydroxy-(10E,12Z)-octadecadienoate + glutathione disulfide + CC H2O; Xref=Rhea:RHEA:76687, ChEBI:CHEBI:15377, ChEBI:CHEBI:57925, CC ChEBI:CHEBI:58297, ChEBI:CHEBI:60955, ChEBI:CHEBI:77852; CC Evidence={ECO:0000250|UniProtKB:P07203}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:76688; CC Evidence={ECO:0000250|UniProtKB:P07203}; CC -!- CATALYTIC ACTIVITY: CC Reaction=(5S)-hydroperoxy-(6E,8Z,11Z,14Z)-eicosatetraenoate + 2 CC glutathione = (5S)-hydroxy-(6E,8Z,11Z,14Z)-eicosatetraenoate + CC glutathione disulfide + H2O; Xref=Rhea:RHEA:48620, ChEBI:CHEBI:15377, CC ChEBI:CHEBI:57450, ChEBI:CHEBI:57925, ChEBI:CHEBI:58297, CC ChEBI:CHEBI:90632; Evidence={ECO:0000250|UniProtKB:P07203}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:48621; CC Evidence={ECO:0000250|UniProtKB:P07203}; CC -!- CATALYTIC ACTIVITY: CC Reaction=(12S)-hydroperoxy-(5Z,8Z,10E,14Z)-eicosatetraenoate + 2 CC glutathione = (12S)-hydroxy-(5Z,8Z,10E,14Z)-eicosatetraenoate + CC glutathione disulfide + H2O; Xref=Rhea:RHEA:50708, ChEBI:CHEBI:15377, CC ChEBI:CHEBI:57444, ChEBI:CHEBI:57925, ChEBI:CHEBI:58297, CC ChEBI:CHEBI:90680; Evidence={ECO:0000269|PubMed:9195979}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:50709; CC Evidence={ECO:0000305|PubMed:9195979}; CC -!- CATALYTIC ACTIVITY: CC Reaction=(12R)-hydroperoxy-(5Z,8Z,10E,14Z)-eicosatetraenoate + 2 CC glutathione = (12R)-hydroxy-(5Z,8Z,10E,14Z)-eicosatetraenoate + CC glutathione disulfide + H2O; Xref=Rhea:RHEA:76691, ChEBI:CHEBI:15377, CC ChEBI:CHEBI:57925, ChEBI:CHEBI:58297, ChEBI:CHEBI:75230, CC ChEBI:CHEBI:83343; Evidence={ECO:0000250|UniProtKB:P07203}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:76692; CC Evidence={ECO:0000250|UniProtKB:P07203}; CC -!- CATALYTIC ACTIVITY: CC Reaction=(15S)-hydroperoxy-(5Z,8Z,11Z,13E)-eicosatetraenoate + 2 CC glutathione = (15S)-hydroxy-(5Z,8Z,11Z,13E)-eicosatetraenoate + CC glutathione disulfide + H2O; Xref=Rhea:RHEA:76695, ChEBI:CHEBI:15377, CC ChEBI:CHEBI:57409, ChEBI:CHEBI:57446, ChEBI:CHEBI:57925, CC ChEBI:CHEBI:58297; Evidence={ECO:0000250|UniProtKB:P07203}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:76696; CC Evidence={ECO:0000250|UniProtKB:P07203}; CC -!- CATALYTIC ACTIVITY: CC Reaction=(5S)-hydroperoxy-(6E,8Z,11Z,14Z,17Z)-eicosapentaenoate + 2 CC glutathione = (5S)-hydroxy-(6E,8Z,11Z,14Z,17Z)-eicosapentaenoate + CC glutathione disulfide + H2O; Xref=Rhea:RHEA:76699, ChEBI:CHEBI:15377, CC ChEBI:CHEBI:57925, ChEBI:CHEBI:58297, ChEBI:CHEBI:195399, CC ChEBI:CHEBI:195400; Evidence={ECO:0000250|UniProtKB:P07203}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:76700; CC Evidence={ECO:0000250|UniProtKB:P07203}; CC -!- CATALYTIC ACTIVITY: CC Reaction=(12S)-hydroperoxy-(5Z,8Z,10E,14Z,17Z)-eicosapentaenoate + 2 CC glutathione = (12S)-hydroxy-(5Z,8Z,10E,14Z,17Z)-eicosapentaenoate + CC glutathione disulfide + H2O; Xref=Rhea:RHEA:76703, ChEBI:CHEBI:15377, CC ChEBI:CHEBI:57925, ChEBI:CHEBI:58297, ChEBI:CHEBI:90772, CC ChEBI:CHEBI:195401; Evidence={ECO:0000250|UniProtKB:P07203}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:76704; CC Evidence={ECO:0000250|UniProtKB:P07203}; CC -!- CATALYTIC ACTIVITY: CC Reaction=(15S)-hydroperoxy-(5Z,8Z,11Z,13E,17Z)-eicosapentaenoate + 2 CC glutathione = (15S)-hydroxy-(5Z,8Z,11Z,13E,17Z)-eicosapentaenoate + CC glutathione disulfide + H2O; Xref=Rhea:RHEA:76707, ChEBI:CHEBI:15377, CC ChEBI:CHEBI:57925, ChEBI:CHEBI:58297, ChEBI:CHEBI:132087, CC ChEBI:CHEBI:194369; Evidence={ECO:0000250|UniProtKB:P07203}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:76708; CC Evidence={ECO:0000250|UniProtKB:P07203}; CC -!- CATALYTIC ACTIVITY: CC Reaction=(15S)-hydroperoxy-(11Z,13E)-eicosadienoate + 2 glutathione = CC (15S)-hydroxy-(11Z,13E)-eicosadienoate + glutathione disulfide + H2O; CC Xref=Rhea:RHEA:76711, ChEBI:CHEBI:15377, ChEBI:CHEBI:57925, CC ChEBI:CHEBI:58297, ChEBI:CHEBI:144832, ChEBI:CHEBI:195402; CC Evidence={ECO:0000250|UniProtKB:P07203}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:76712; CC Evidence={ECO:0000250|UniProtKB:P07203}; CC -!- CATALYTIC ACTIVITY: CC Reaction=(17S)-hydroperoxy-(4Z,7Z,10Z,13Z,15E,19Z)-docosahexaenoate + 2 CC glutathione = (17S)-hydroxy-(4Z,7Z,10Z,13Z,15E,19Z)-docosahexaenoate CC + glutathione disulfide + H2O; Xref=Rhea:RHEA:76715, CC ChEBI:CHEBI:15377, ChEBI:CHEBI:57925, ChEBI:CHEBI:58297, CC ChEBI:CHEBI:133795, ChEBI:CHEBI:195403; CC Evidence={ECO:0000250|UniProtKB:P07203}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:76716; CC Evidence={ECO:0000250|UniProtKB:P07203}; CC -!- BIOPHYSICOCHEMICAL PROPERTIES: CC Kinetic parameters: CC KM=14 uM for H(2)O(2) (at 25 degrees Celsius, in 0.1 M phosphate CC buffer, pH 7.0) {ECO:0000269|PubMed:21420488}; CC KM=29 uM for tert-butylperoxide (at 25 degrees Celsius, in 0.1 M CC phosphate buffer, pH 7.0) {ECO:0000269|PubMed:21420488}; CC Vmax=319 mM/min/mg enzyme toward H(2)O(2) (at 25 degrees Celsius, in CC 0.1 M phosphate buffer, pH 7.0) {ECO:0000269|PubMed:21420488}; CC Vmax=182 mM/min/mg enzyme toward tert-butylperoxide (at 25 degrees CC Celsius, in 0.1 M phosphate buffer, pH 7.0) CC {ECO:0000269|PubMed:21420488}; CC -!- SUBUNIT: Homotetramer. Interacts with MIEN1. CC {ECO:0000269|PubMed:17503775}. CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:10754271, CC ECO:0000269|PubMed:9126277}. Mitochondrion CC {ECO:0000269|PubMed:10754271, ECO:0000269|PubMed:9126277}. CC -!- TISSUE SPECIFICITY: Expressed in liver, kidney, lung, brain and heart. CC {ECO:0000269|PubMed:10754271, ECO:0000269|PubMed:9126277, CC ECO:0000269|PubMed:9195979, ECO:0000269|PubMed:9712879}. CC -!- PTM: During periods of oxidative stress, Sec-47 may react with a CC superoxide radical, irreversibly lose hydroselenide and be converted to CC dehydroalanine. {ECO:0000269|PubMed:21420488}. CC -!- DISRUPTION PHENOTYPE: Mutants are healthy, fertile and show no CC increased sensitivity to hyperoxia (PubMed:9195979). Mice display CC enhanced susceptibility to paraquat and cortical neurons from Gpx1- CC deficient mice are more susceptible to H2O2-mediated toxicity than CC neurons from wild-type mice (PubMed:9712879). Gpx1-deficient mice are CC smaller than wild type littermates and the liver has increased CC mitochondrial H2O2 production, increased lipid peroxides, and decreased CC mitochondrial energy output (PubMed:10754271). CC {ECO:0000269|PubMed:10754271, ECO:0000269|PubMed:9195979, CC ECO:0000269|PubMed:9712879}. CC -!- MISCELLANEOUS: In the absence of Sod1, Gpx1 in the liver undergoes a CC 40% reduction in catalytic activity as a result of the decomposition of CC Sec-47 to dehydroalanine. {ECO:0000305|PubMed:21420488}. CC -!- SIMILARITY: Belongs to the glutathione peroxidase family. CC {ECO:0000305}. CC -!- CAUTION: PubMed:2771650 sequence was originally thought to originate CC from human. {ECO:0000305}. CC -!- SEQUENCE CAUTION: CC Sequence=CAB43535.1; Type=Miscellaneous discrepancy; Note=Number of sequencing artifacts.; Evidence={ECO:0000305}; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; X03920; CAA27558.1; -; Genomic_DNA. DR EMBL; AK002245; BAC55244.1; -; mRNA. DR EMBL; AK010999; BAC55252.1; -; mRNA. DR EMBL; AK011019; BAC55253.1; -; mRNA. DR EMBL; AK028171; BAC55257.1; -; mRNA. DR EMBL; AK150548; BAE29650.1; -; mRNA. DR EMBL; AK154833; BAE32862.1; -; mRNA. DR EMBL; AK160388; BAE35760.1; -; mRNA. DR EMBL; BC086649; AAH86649.1; -; mRNA. DR EMBL; X15667; CAB43535.1; ALT_SEQ; mRNA. DR CCDS; CCDS23522.1; -. DR PIR; A25106; OPMSE. DR PIR; S05317; S05317. DR RefSeq; NP_001316456.1; NM_001329527.1. DR RefSeq; NP_001316457.1; NM_001329528.1. DR RefSeq; NP_032186.2; NM_008160.6. DR BioGRID; 200037; 8. DR IntAct; P11352; 4. DR STRING; 10090.ENSMUSP00000081010; -. DR SwissLipids; SLP:000001635; -. DR PeroxiBase; 3709; MmGPx01. DR iPTMnet; P11352; -. DR PhosphoSitePlus; P11352; -. DR SwissPalm; P11352; -. DR REPRODUCTION-2DPAGE; IPI00319652; -. DR REPRODUCTION-2DPAGE; P11352; -. DR CPTAC; non-CPTAC-3983; -. DR EPD; P11352; -. DR jPOST; P11352; -. DR MaxQB; P11352; -. DR PaxDb; 10090-ENSMUSP00000081010; -. DR PeptideAtlas; P11352; -. DR ProteomicsDB; 269627; -. DR Pumba; P11352; -. DR Antibodypedia; 39716; 621 antibodies from 40 providers. DR DNASU; 14775; -. DR Ensembl; ENSMUST00000082429.8; ENSMUSP00000081010.7; ENSMUSG00000063856.9. DR GeneID; 14775; -. DR KEGG; mmu:14775; -. DR UCSC; uc009rpf.3; mouse. DR AGR; MGI:104887; -. DR CTD; 2876; -. DR MGI; MGI:104887; Gpx1. DR VEuPathDB; HostDB:ENSMUSG00000063856; -. DR eggNOG; KOG1651; Eukaryota. DR GeneTree; ENSGT00940000156150; -. DR InParanoid; P11352; -. DR OMA; RDYTEMN; -. DR OrthoDB; 67394at2759; -. DR PhylomeDB; P11352; -. DR TreeFam; TF105318; -. DR Reactome; R-MMU-2142712; Synthesis of 12-eicosatetraenoic acid derivatives. DR Reactome; R-MMU-2142770; Synthesis of 15-eicosatetraenoic acid derivatives. DR Reactome; R-MMU-3299685; Detoxification of Reactive Oxygen Species. DR SABIO-RK; P11352; -. DR BioGRID-ORCS; 14775; 6 hits in 81 CRISPR screens. DR ChiTaRS; Gpx1; mouse. DR PRO; PR:P11352; -. DR Proteomes; UP000000589; Chromosome 9. DR RNAct; P11352; Protein. DR Bgee; ENSMUSG00000063856; Expressed in fetal liver hematopoietic progenitor cell and 259 other cell types or tissues. DR ExpressionAtlas; P11352; baseline and differential. DR GO; GO:0005737; C:cytoplasm; ISS:BHF-UCL. DR GO; GO:0005829; C:cytosol; IDA:UniProtKB. DR GO; GO:0097413; C:Lewy body; IEA:Ensembl. DR GO; GO:0005739; C:mitochondrion; IDA:MGI. DR GO; GO:0004602; F:glutathione peroxidase activity; IDA:MGI. DR GO; GO:0004601; F:peroxidase activity; IDA:UniProtKB. DR GO; GO:0047066; F:phospholipid-hydroperoxide glutathione peroxidase activity; ISS:UniProtKB. DR GO; GO:0017124; F:SH3 domain binding; ISO:MGI. DR GO; GO:0060055; P:angiogenesis involved in wound healing; IMP:MGI. DR GO; GO:0006915; P:apoptotic process; IMP:MGI. DR GO; GO:0019369; P:arachidonic acid metabolic process; IMP:UniProtKB. DR GO; GO:0051702; P:biological process involved in interaction with symbiont; IGI:MGI. DR GO; GO:0043534; P:blood vessel endothelial cell migration; IMP:MGI. DR GO; GO:0045454; P:cell redox homeostasis; ISO:MGI. DR GO; GO:0071333; P:cellular response to glucose stimulus; ISO:MGI. DR GO; GO:0001885; P:endothelial cell development; IMP:MGI. DR GO; GO:0040029; P:epigenetic regulation of gene expression; ISO:MGI. DR GO; GO:0045444; P:fat cell differentiation; IMP:MGI. DR GO; GO:0048144; P:fibroblast proliferation; IMP:MGI. DR GO; GO:0006749; P:glutathione metabolic process; ISO:MGI. DR GO; GO:0060047; P:heart contraction; IMP:MGI. DR GO; GO:0042744; P:hydrogen peroxide catabolic process; IMP:MGI. DR GO; GO:0008631; P:intrinsic apoptotic signaling pathway in response to oxidative stress; IMP:MGI. DR GO; GO:0006629; P:lipid metabolic process; IMP:MGI. DR GO; GO:0019372; P:lipoxygenase pathway; ISS:UniProtKB. DR GO; GO:0045445; P:myoblast differentiation; IMP:MGI. DR GO; GO:0051450; P:myoblast proliferation; IMP:MGI. DR GO; GO:0014902; P:myotube differentiation; IMP:MGI. DR GO; GO:1902042; P:negative regulation of extrinsic apoptotic signaling pathway via death domain receptors; ISO:MGI. DR GO; GO:0002862; P:negative regulation of inflammatory response to antigenic stimulus; IGI:MGI. DR GO; GO:1902176; P:negative regulation of oxidative stress-induced intrinsic apoptotic signaling pathway; IMP:MGI. DR GO; GO:0090201; P:negative regulation of release of cytochrome c from mitochondria; ISO:MGI. DR GO; GO:0051402; P:neuron apoptotic process; IMP:MGI. DR GO; GO:0051897; P:positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction; IMP:MGI. DR GO; GO:0033599; P:regulation of mammary gland epithelial cell proliferation; ISO:MGI. DR GO; GO:0061136; P:regulation of proteasomal protein catabolic process; ISO:MGI. DR GO; GO:0032355; P:response to estradiol; IEA:Ensembl. DR GO; GO:0051593; P:response to folic acid; IEA:Ensembl. DR GO; GO:0010332; P:response to gamma radiation; IGI:MGI. DR GO; GO:0009725; P:response to hormone; IEA:Ensembl. DR GO; GO:0042542; P:response to hydrogen peroxide; IMP:MGI. DR GO; GO:0033194; P:response to hydroperoxide; IMP:MGI. DR GO; GO:0035094; P:response to nicotine; IEA:Ensembl. DR GO; GO:0006979; P:response to oxidative stress; IMP:MGI. DR GO; GO:0000302; P:response to reactive oxygen species; IMP:MGI. DR GO; GO:0010269; P:response to selenium ion; ISO:MGI. DR GO; GO:0009609; P:response to symbiotic bacterium; IGI:MGI. DR GO; GO:0009636; P:response to toxic substance; IMP:MGI. DR GO; GO:0033197; P:response to vitamin E; IEA:Ensembl. DR GO; GO:0009611; P:response to wounding; IMP:MGI. DR GO; GO:0009410; P:response to xenobiotic stimulus; IMP:MGI. DR GO; GO:0007605; P:sensory perception of sound; IMP:MGI. DR GO; GO:0048741; P:skeletal muscle fiber development; IMP:MGI. DR GO; GO:0043403; P:skeletal muscle tissue regeneration; IMP:MGI. DR GO; GO:0001659; P:temperature homeostasis; IGI:MGI. DR GO; GO:0006641; P:triglyceride metabolic process; IMP:MGI. DR GO; GO:0009650; P:UV protection; ISO:MGI. DR GO; GO:0042311; P:vasodilation; IMP:MGI. DR CDD; cd00340; GSH_Peroxidase; 1. DR Gene3D; 3.40.30.10; Glutaredoxin; 1. DR InterPro; IPR000889; Glutathione_peroxidase. DR InterPro; IPR029759; GPX_AS. DR InterPro; IPR029760; GPX_CS. DR InterPro; IPR036249; Thioredoxin-like_sf. DR PANTHER; PTHR11592; GLUTATHIONE PEROXIDASE; 1. DR PANTHER; PTHR11592:SF41; GLUTATHIONE PEROXIDASE 1; 1. DR Pfam; PF00255; GSHPx; 1. DR PIRSF; PIRSF000303; Glutathion_perox; 1. DR PRINTS; PR01011; GLUTPROXDASE. DR SUPFAM; SSF52833; Thioredoxin-like; 1. DR PROSITE; PS00460; GLUTATHIONE_PEROXID_1; 1. DR PROSITE; PS00763; GLUTATHIONE_PEROXID_2; 1. DR PROSITE; PS51355; GLUTATHIONE_PEROXID_3; 1. DR SWISS-2DPAGE; P11352; -. DR Genevisible; P11352; MM. PE 1: Evidence at protein level; KW Acetylation; Cytoplasm; Lipid metabolism; Mitochondrion; Oxidoreductase; KW Peroxidase; Phosphoprotein; Reference proteome; Selenocysteine. FT CHAIN 1..201 FT /note="Glutathione peroxidase 1" FT /id="PRO_0000066613" FT ACT_SITE 47 FT /evidence="ECO:0000250|UniProtKB:O70325" FT SITE 47 FT /note="Subject to oxidation and hydroselenide loss to FT dehydroalanine" FT NON_STD 47 FT /note="Selenocysteine" FT /evidence="ECO:0000269|PubMed:32358195" FT MOD_RES 7 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:17242355" FT MOD_RES 32 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:P04041" FT MOD_RES 62 FT /note="N6-acetyllysine; alternate" FT /evidence="ECO:0007744|PubMed:23576753" FT MOD_RES 62 FT /note="N6-succinyllysine; alternate" FT /evidence="ECO:0007744|PubMed:23806337" FT MOD_RES 86 FT /note="N6-acetyllysine; alternate" FT /evidence="ECO:0007744|PubMed:23576753" FT MOD_RES 86 FT /note="N6-succinyllysine; alternate" FT /evidence="ECO:0007744|PubMed:23806337" FT MOD_RES 112 FT /note="N6-acetyllysine; alternate" FT /evidence="ECO:0007744|PubMed:23576753" FT MOD_RES 112 FT /note="N6-succinyllysine; alternate" FT /evidence="ECO:0007744|PubMed:23806337" FT MOD_RES 119 FT /note="N6-acetyllysine" FT /evidence="ECO:0007744|PubMed:23576753" FT MOD_RES 146 FT /note="N6-acetyllysine; alternate" FT /evidence="ECO:0007744|PubMed:23576753" FT MOD_RES 146 FT /note="N6-succinyllysine; alternate" FT /evidence="ECO:0007744|PubMed:23806337" FT MOD_RES 195 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:P04041" SQ SEQUENCE 201 AA; 22329 MW; 401D065165D8AF5C CRC64; MCAARLSAAA QSTVYAFSAR PLTGGEPVSL GSLRGKVLLI ENVASLUGTT IRDYTEMNDL QKRLGPRGLV VLGFPCNQFG HQENGKNEEI LNSLKYVRPG GGFEPNFTLF EKCEVNGEKA HPLFTFLRNA LPTPSDDPTA LMTDPKYIIW SPVCRNDIAW NFEKFLVGPD GVPVRRYSRR FRTIDIEPDI ETLLSQQSGN S //