ID GPX3_HUMAN Reviewed; 226 AA.
AC P22352; O43787; Q86W78; Q9NZ74; Q9UEL1;
DT 01-AUG-1991, integrated into UniProtKB/Swiss-Prot.
DT 26-FEB-2008, sequence version 2.
DT 24-JAN-2024, entry version 215.
DE RecName: Full=Glutathione peroxidase 3 {ECO:0000305};
DE Short=GPx-3;
DE Short=GSHPx-3;
DE EC=1.11.1.9 {ECO:0000269|PubMed:1897960};
DE AltName: Full=Extracellular glutathione peroxidase;
DE AltName: Full=Plasma glutathione peroxidase;
DE Short=GPx-P;
DE Short=GSHPx-P;
DE Flags: Precursor;
GN Name=GPX3 {ECO:0000312|HGNC:HGNC:4555}; Synonyms=GPXP;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], AND PARTIAL PROTEIN SEQUENCE.
RC TISSUE=Fetal liver, and Placenta;
RX PubMed=2229017; DOI=10.1093/oxfordjournals.jbchem.a123172;
RA Takahashi K., Akasaka M., Yamamoto Y., Kobayashi C., Mizoguchi J.,
RA Koyama J.;
RT "Primary structure of human plasma glutathione peroxidase deduced from cDNA
RT sequences.";
RL J. Biochem. 108:145-148(1990).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Kidney;
RX PubMed=1339300;
RA Chu F.-F., Esworthy R.S., Doroshow J.H., Doan K., Liu X.F.;
RT "Expression of plasma glutathione peroxidase in human liver in addition to
RT kidney, heart, lung, and breast in humans and rodents.";
RL Blood 79:3233-3238(1992).
RN [3]
RP SEQUENCE REVISION TO 73.
RA Chu F.-F.;
RL Submitted (NOV-2010) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC TISSUE=Lymphocyte;
RX PubMed=8056346; DOI=10.1016/0378-1119(94)90023-x;
RA Yoshimura S., Suemizu H., Taniguchi Y., Arimori K., Kawabe N., Moriuchi T.;
RT "The human plasma glutathione peroxidase-encoding gene: organization,
RT sequence and localization to chromosome 5q32.";
RL Gene 145:293-297(1994).
RN [5]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=10970826; DOI=10.1165/ajrcmb.23.3.4076;
RA Comhair S.A.A., Thomassen M.J., Erzurum S.C.;
RT "Differential induction of extracellular glutathione peroxidase and nitric
RT oxide synthase 2 in airways of healthy individuals exposed to 100% O(2) or
RT cigarette smoke.";
RL Am. J. Respir. Cell Mol. Biol. 23:350-354(2000).
RN [6]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANT LEU-128.
RG NIEHS SNPs program;
RL Submitted (MAY-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., Buhay C.J.,
RA Chen R., Cree A., Ding Y., Dugan-Rocha S., Gill R., Gunaratne P.,
RA Harris R.A., Hawes A.C., Hernandez J., Hodgson A.V., Hume J., Jackson A.,
RA Khan Z.M., Kovar-Smith C., Lewis L.R., Lozado R.J., Metzker M.L.,
RA Milosavljevic A., Miner G.R., Morgan M.B., Nazareth L.V., Scott G.,
RA Sodergren E., Song X.-Z., Steffen D., Wei S., Wheeler D.A., Wright M.W.,
RA Worley K.C., Yuan Y., Zhang Z., Adams C.Q., Ansari-Lari M.A., Ayele M.,
RA Brown M.J., Chen G., Chen Z., Clendenning J., Clerc-Blankenburg K.P.,
RA Chen R., Chen Z., Davis C., Delgado O., Dinh H.H., Dong W., Draper H.,
RA Ernst S., Fu G., Gonzalez-Garay M.L., Garcia D.K., Gillett W., Gu J.,
RA Hao B., Haugen E., Havlak P., He X., Hennig S., Hu S., Huang W.,
RA Jackson L.R., Jacob L.S., Kelly S.H., Kube M., Levy R., Li Z., Liu B.,
RA Liu J., Liu W., Lu J., Maheshwari M., Nguyen B.-V., Okwuonu G.O.,
RA Palmeiri A., 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., Zhang X.,
RA Zhao G., Zhou J., Zhou Y., Nelson D., Lehrach H., Reinhardt R.,
RA Naylor S.L., Yang H., Olson M., Weinstock G., 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=Duodenum, Lung, and Pancreas;
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 [9]
RP PROTEIN SEQUENCE OF 107-138 AND 148-175, FUNCTION, AND CATALYTIC ACTIVITY.
RX PubMed=1897960; DOI=10.1016/0003-9861(91)90048-n;
RA Esworthy R.S., Chu F.-F., Paxton R.J., Akman S., Doroshow J.H.;
RT "Characterization and partial amino acid sequence of human plasma
RT glutathione peroxidase.";
RL Arch. Biochem. Biophys. 286:330-336(1991).
RN [10]
RP X-RAY CRYSTALLOGRAPHY (1.85 ANGSTROMS) OF 25-223.
RG Structural genomics consortium (SGC);
RT "Crystal structure of human glutathione peroxidase 3 (selenocysteine to
RT glycine mutant).";
RL Submitted (SEP-2007) to the PDB data bank.
CC -!- FUNCTION: Protects cells and enzymes from oxidative damage, by
CC catalyzing the reduction of hydrogen peroxide, lipid peroxides and
CC organic hydroperoxide, by glutathione. {ECO:0000269|PubMed:1897960}.
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:1897960};
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:1897960};
CC -!- SUBUNIT: Homotetramer.
CC -!- INTERACTION:
CC P22352; Q9UMX0-2: UBQLN1; NbExp=3; IntAct=EBI-2832946, EBI-10173939;
CC -!- SUBCELLULAR LOCATION: Secreted.
CC -!- TISSUE SPECIFICITY: Secreted in plasma.
CC -!- PTM: The N-terminus is blocked.
CC -!- SIMILARITY: Belongs to the glutathione peroxidase family.
CC {ECO:0000305}.
CC -!- WEB RESOURCE: Name=NIEHS-SNPs;
CC URL="http://egp.gs.washington.edu/data/gpx3/";
CC -!- WEB RESOURCE: Name=Wikipedia; Note=Glutathione peroxidase entry;
CC URL="https://en.wikipedia.org/wiki/Glutathione_peroxidase";
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DR EMBL; D00632; BAA00525.1; -; mRNA.
DR EMBL; X58295; CAA41228.2; -; mRNA.
DR EMBL; D16360; BAA03862.1; -; Genomic_DNA.
DR EMBL; D16361; BAA03863.2; -; Genomic_DNA.
DR EMBL; D16362; BAA03864.1; -; Genomic_DNA.
DR EMBL; AF217787; AAF43005.1; -; mRNA.
DR EMBL; AY310878; AAP50261.1; -; Genomic_DNA.
DR EMBL; AC008641; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC013601; AAH13601.1; -; mRNA.
DR EMBL; BC035841; AAH35841.1; -; mRNA.
DR EMBL; BC050378; AAH50378.2; -; mRNA.
DR CCDS; CCDS43389.1; -.
DR PIR; I53822; JQ0476.
DR RefSeq; NP_001316719.1; NM_001329790.1.
DR RefSeq; NP_002075.2; NM_002084.4.
DR PDB; 2R37; X-ray; 1.85 A; A/B=25-223.
DR PDBsum; 2R37; -.
DR SMR; P22352; -.
DR BioGRID; 109136; 12.
DR IntAct; P22352; 7.
DR STRING; 9606.ENSP00000373477; -.
DR DrugBank; DB09096; Benzoyl peroxide.
DR DrugBank; DB00143; Glutathione.
DR DrugBank; DB03310; Glutathione disulfide.
DR PeroxiBase; 3602; HsGPx03.
DR iPTMnet; P22352; -.
DR PhosphoSitePlus; P22352; -.
DR BioMuta; GPX3; -.
DR DMDM; 172046796; -.
DR REPRODUCTION-2DPAGE; IPI00026199; -.
DR SWISS-2DPAGE; P22352; -.
DR EPD; P22352; -.
DR jPOST; P22352; -.
DR MassIVE; P22352; -.
DR MaxQB; P22352; -.
DR PaxDb; 9606-ENSP00000373477; -.
DR PeptideAtlas; P22352; -.
DR ProteomicsDB; 53984; -.
DR Antibodypedia; 8091; 288 antibodies from 32 providers.
DR DNASU; 2878; -.
DR Ensembl; ENST00000388825.9; ENSP00000373477.4; ENSG00000211445.13.
DR GeneID; 2878; -.
DR KEGG; hsa:2878; -.
DR MANE-Select; ENST00000388825.9; ENSP00000373477.4; NM_002084.5; NP_002075.2.
DR UCSC; uc021yga.2; human.
DR AGR; HGNC:4555; -.
DR CTD; 2878; -.
DR DisGeNET; 2878; -.
DR GeneCards; GPX3; -.
DR HGNC; HGNC:4555; GPX3.
DR HPA; ENSG00000211445; Tissue enhanced (kidney).
DR MIM; 138321; gene.
DR neXtProt; NX_P22352; -.
DR OpenTargets; ENSG00000211445; -.
DR PharmGKB; PA28951; -.
DR VEuPathDB; HostDB:ENSG00000211445; -.
DR eggNOG; KOG1651; Eukaryota.
DR GeneTree; ENSGT00940000161754; -.
DR HOGENOM; CLU_029507_2_1_1; -.
DR InParanoid; P22352; -.
DR OMA; KTDCHAG; -.
DR OrthoDB; 67394at2759; -.
DR PhylomeDB; P22352; -.
DR TreeFam; TF105318; -.
DR BioCyc; MetaCyc:HS08224-MONOMER; -.
DR BRENDA; 1.11.1.9; 2681.
DR PathwayCommons; P22352; -.
DR Reactome; R-HSA-3299685; Detoxification of Reactive Oxygen Species.
DR SignaLink; P22352; -.
DR BioGRID-ORCS; 2878; 13 hits in 1155 CRISPR screens.
DR ChiTaRS; GPX3; human.
DR EvolutionaryTrace; P22352; -.
DR GeneWiki; GPX3; -.
DR GenomeRNAi; 2878; -.
DR Pharos; P22352; Tbio.
DR PRO; PR:P22352; -.
DR Proteomes; UP000005640; Chromosome 5.
DR RNAct; P22352; Protein.
DR Bgee; ENSG00000211445; Expressed in adult organism and 201 other cell types or tissues.
DR ExpressionAtlas; P22352; baseline and differential.
DR Genevisible; P22352; HS.
DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR GO; GO:0005576; C:extracellular region; TAS:Reactome.
DR GO; GO:0005615; C:extracellular space; IDA:UniProtKB.
DR GO; GO:0004602; F:glutathione peroxidase activity; IDA:UniProtKB.
DR GO; GO:0042802; F:identical protein binding; IPI:UniProtKB.
DR GO; GO:0008430; F:selenium binding; IDA:UniProtKB.
DR GO; GO:0042744; P:hydrogen peroxide catabolic process; IBA:GO_Central.
DR GO; GO:0006982; P:response to lipid hydroperoxide; TAS:UniProtKB.
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:SF32; GLUTATHIONE PEROXIDASE 3; 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.
PE 1: Evidence at protein level;
KW 3D-structure; Direct protein sequencing; Oxidoreductase; Peroxidase;
KW Reference proteome; Secreted; Selenocysteine; Signal.
FT SIGNAL 1..20
FT /evidence="ECO:0000255"
FT CHAIN 21..226
FT /note="Glutathione peroxidase 3"
FT /id="PRO_0000013062"
FT ACT_SITE 73
FT NON_STD 73
FT /note="Selenocysteine"
FT /evidence="ECO:0000269|PubMed:2229017"
FT VARIANT 128
FT /note="F -> L (in dbSNP:rs8177445)"
FT /evidence="ECO:0000269|Ref.6"
FT /id="VAR_020943"
FT HELIX 40..42
FT /evidence="ECO:0007829|PDB:2R37"
FT STRAND 44..47
FT /evidence="ECO:0007829|PDB:2R37"
FT STRAND 53..55
FT /evidence="ECO:0007829|PDB:2R37"
FT HELIX 56..59
FT /evidence="ECO:0007829|PDB:2R37"
FT STRAND 62..69
FT /evidence="ECO:0007829|PDB:2R37"
FT STRAND 71..73
FT /evidence="ECO:0007829|PDB:2R37"
FT TURN 74..77
FT /evidence="ECO:0007829|PDB:2R37"
FT HELIX 78..89
FT /evidence="ECO:0007829|PDB:2R37"
FT HELIX 90..92
FT /evidence="ECO:0007829|PDB:2R37"
FT STRAND 94..100
FT /evidence="ECO:0007829|PDB:2R37"
FT HELIX 112..114
FT /evidence="ECO:0007829|PDB:2R37"
FT HELIX 115..121
FT /evidence="ECO:0007829|PDB:2R37"
FT STRAND 131..135
FT /evidence="ECO:0007829|PDB:2R37"
FT STRAND 140..142
FT /evidence="ECO:0007829|PDB:2R37"
FT HELIX 147..155
FT /evidence="ECO:0007829|PDB:2R37"
FT HELIX 166..168
FT /evidence="ECO:0007829|PDB:2R37"
FT STRAND 185..188
FT /evidence="ECO:0007829|PDB:2R37"
FT STRAND 194..198
FT /evidence="ECO:0007829|PDB:2R37"
FT HELIX 204..223
FT /evidence="ECO:0007829|PDB:2R37"
SQ SEQUENCE 226 AA; 25552 MW; A839E87A5CDB51A9 CRC64;
MARLLQASCL LSLLLAGFVS QSRGQEKSKM DCHGGISGTI YEYGALTIDG EEYIPFKQYA
GKYVLFVNVA SYUGLTGQYI ELNALQEELA PFGLVILGFP CNQFGKQEPG ENSEILPTLK
YVRPGGGFVP NFQLFEKGDV NGEKEQKFYT FLKNSCPPTS ELLGTSDRLF WEPMKVHDIR
WNFEKFLVGP DGIPIMRWHH RTTVSNVKMD ILSYMRRQAA LGVKRK
//
