GPX2_HUMAN
ID GPX2_HUMAN Reviewed; 190 AA.
AC P18283; Q6PJ52; Q8WWI7; Q9NRP9;
DT 01-NOV-1990, integrated into UniProtKB/Swiss-Prot.
DT 26-FEB-2008, sequence version 3.
DT 03-AUG-2022, entry version 197.
DE RecName: Full=Glutathione peroxidase 2;
DE Short=GPx-2;
DE Short=GSHPx-2;
DE EC=1.11.1.9 {ECO:0000269|PubMed:8428933};
DE AltName: Full=Gastrointestinal glutathione peroxidase;
DE AltName: Full=Glutathione peroxidase-gastrointestinal {ECO:0000303|PubMed:8428933};
DE Short=GPx-GI {ECO:0000303|PubMed:8428933};
DE Short=GSHPx-GI {ECO:0000303|PubMed:8428933};
DE AltName: Full=Glutathione peroxidase-related protein 2;
DE Short=GPRP-2;
GN Name=GPX2 {ECO:0000303|Ref.8, ECO:0000312|HGNC:HGNC:4554};
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].
RC TISSUE=Liver;
RX PubMed=2388849; DOI=10.1093/nar/18.15.4619;
RA Akasaka M., Mizoguchi J., Takahashi K.;
RT "A human cDNA sequence of a novel glutathione peroxidase-related protein.";
RL Nucleic Acids Res. 18:4619-4619(1990).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, CATALYTIC ACTIVITY, SUBCELLULAR
RP LOCATION, AND TISSUE SPECIFICITY.
RC TISSUE=Liver;
RX PubMed=8428933; DOI=10.1016/s0021-9258(18)53812-6;
RA Chu F.-F., Doroshow J.H., Esworthy R.S.;
RT "Expression, characterization, and tissue distribution of a new cellular
RT selenium-dependent glutathione peroxidase, GSHPx-GI.";
RL J. Biol. Chem. 268:2571-2576(1993).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANT LEU-37.
RX PubMed=10806356; DOI=10.1016/s0378-1119(00)00137-2;
RA Kelner M.J., Bagnell R.D., Montoya M.A., Lanham K.A.;
RT "Structural organization of the human gastrointestinal glutathione
RT peroxidase (GPX2) promoter and 3'-nontranscribed region: transcriptional
RT response to exogenous redox agents.";
RL Gene 248:109-116(2000).
RN [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS LEU-126 AND CYS-146.
RG NIEHS SNPs program;
RL Submitted (OCT-2004) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=12508121; DOI=10.1038/nature01348;
RA Heilig R., Eckenberg R., Petit J.-L., Fonknechten N., Da Silva C.,
RA Cattolico L., Levy M., Barbe V., De Berardinis V., Ureta-Vidal A.,
RA Pelletier E., Vico V., Anthouard V., Rowen L., Madan A., Qin S., Sun H.,
RA Du H., Pepin K., Artiguenave F., Robert C., Cruaud C., Bruels T.,
RA Jaillon O., Friedlander L., Samson G., Brottier P., Cure S., Segurens B.,
RA Aniere F., Samain S., Crespeau H., Abbasi N., Aiach N., Boscus D.,
RA Dickhoff R., Dors M., Dubois I., Friedman C., Gouyvenoux M., James R.,
RA Madan A., Mairey-Estrada B., Mangenot S., Martins N., Menard M., Oztas S.,
RA Ratcliffe A., Shaffer T., Trask B., Vacherie B., Bellemere C., Belser C.,
RA Besnard-Gonnet M., Bartol-Mavel D., Boutard M., Briez-Silla S.,
RA Combette S., Dufosse-Laurent V., Ferron C., Lechaplais C., Louesse C.,
RA Muselet D., Magdelenat G., Pateau E., Petit E., Sirvain-Trukniewicz P.,
RA Trybou A., Vega-Czarny N., Bataille E., Bluet E., Bordelais I., Dubois M.,
RA Dumont C., Guerin T., Haffray S., Hammadi R., Muanga J., Pellouin V.,
RA Robert D., Wunderle E., Gauguet G., Roy A., Sainte-Marthe L., Verdier J.,
RA Verdier-Discala C., Hillier L.W., Fulton L., McPherson J., Matsuda F.,
RA Wilson R., Scarpelli C., Gyapay G., Wincker P., Saurin W., Quetier F.,
RA Waterston R., Hood L., Weissenbach J.;
RT "The DNA sequence and analysis of human chromosome 14.";
RL Nature 421:601-607(2003).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain, Prostate, and Urinary bladder;
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 [7]
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., Buerckstuemmer T.,
RA 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 [8]
RP X-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS) OF 4-188.
RG Structural genomics consortium (SGC);
RT "Crystal structure of the selenocysteine to cysteine mutant of human
RT glutathione peroxidase 2 (GPX2).";
RL Submitted (FEB-2009) to the PDB data bank.
CC -!- FUNCTION: Could play a major role in protecting mammals from the
CC toxicity of ingested organic hydroperoxides (PubMed:8428933). Tert-
CC butyl hydroperoxide, cumene hydroperoxide and linoleic acid
CC hydroperoxide but not phosphatidycholine hydroperoxide, can act as
CC acceptors (PubMed:8428933). {ECO:0000269|PubMed:8428933}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a hydroperoxide + 2 glutathione = an alcohol + glutathione
CC disulfide + H2O; Xref=Rhea:RHEA:62632, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:30879, ChEBI:CHEBI:35924, ChEBI:CHEBI:57925,
CC ChEBI:CHEBI:58297; Evidence={ECO:0000269|PubMed:8428933};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:62633;
CC Evidence={ECO:0000269|PubMed:8428933};
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:8428933};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:16834;
CC Evidence={ECO:0000269|PubMed:8428933};
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:8428933};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:69413;
CC Evidence={ECO:0000269|PubMed:8428933};
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:8428933};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:69652;
CC Evidence={ECO:0000269|PubMed:8428933};
CC -!- SUBUNIT: Homotetramer. {ECO:0000269|PubMed:8428933}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytosol {ECO:0000269|PubMed:8428933}.
CC -!- TISSUE SPECIFICITY: Mostly in liver and gastrointestinal tract, not
CC found in heart or kidney. {ECO:0000269|PubMed:8428933}.
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/gpx2/";
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DR EMBL; X53463; CAB43534.1; -; mRNA.
DR EMBL; X68314; CAA48394.1; -; mRNA.
DR EMBL; AF199441; AAF74026.1; -; Genomic_DNA.
DR EMBL; AY785560; AAV31780.1; -; Genomic_DNA.
DR EMBL; AL139022; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC005277; AAH05277.1; -; mRNA.
DR EMBL; BC016756; AAH16756.1; -; mRNA.
DR EMBL; BC022820; AAH22820.2; -; mRNA.
DR EMBL; BC067221; AAH67221.1; -; mRNA.
DR CCDS; CCDS41964.1; -.
DR PIR; A45207; A45207.
DR RefSeq; NP_002074.2; NM_002083.3.
DR PDB; 2HE3; X-ray; 2.10 A; A=4-188.
DR PDBsum; 2HE3; -.
DR SMR; P18283; -.
DR BioGRID; 109135; 3.
DR IntAct; P18283; 4.
DR MINT; P18283; -.
DR STRING; 9606.ENSP00000374265; -.
DR DrugBank; DB09096; Benzoyl peroxide.
DR DrugBank; DB00143; Glutathione.
DR DrugBank; DB03310; Glutathione disulfide.
DR PeroxiBase; 3601; HsGPx02.
DR iPTMnet; P18283; -.
DR PhosphoSitePlus; P18283; -.
DR BioMuta; GPX2; -.
DR DMDM; 172046064; -.
DR jPOST; P18283; -.
DR MassIVE; P18283; -.
DR MaxQB; P18283; -.
DR PaxDb; P18283; -.
DR PeptideAtlas; P18283; -.
DR PRIDE; P18283; -.
DR ProteomicsDB; 53556; -.
DR Antibodypedia; 47304; 191 antibodies from 31 providers.
DR DNASU; 2877; -.
DR Ensembl; ENST00000389614.6; ENSP00000374265.5; ENSG00000176153.13.
DR GeneID; 2877; -.
DR KEGG; hsa:2877; -.
DR MANE-Select; ENST00000389614.6; ENSP00000374265.5; NM_002083.4; NP_002074.2.
DR UCSC; uc021ruq.3; human.
DR CTD; 2877; -.
DR DisGeNET; 2877; -.
DR GeneCards; GPX2; -.
DR HGNC; HGNC:4554; GPX2.
DR HPA; ENSG00000176153; Tissue enhanced (gallbladder, intestine, liver, stomach, urinary bladder).
DR MIM; 138319; gene.
DR neXtProt; NX_P18283; -.
DR OpenTargets; ENSG00000176153; -.
DR PharmGKB; PA28950; -.
DR VEuPathDB; HostDB:ENSG00000176153; -.
DR eggNOG; KOG1651; Eukaryota.
DR GeneTree; ENSGT00940000160477; -.
DR HOGENOM; CLU_029507_2_0_1; -.
DR InParanoid; P18283; -.
DR OMA; RYSRTFH; -.
DR OrthoDB; 1326471at2759; -.
DR PhylomeDB; P18283; -.
DR TreeFam; TF105318; -.
DR BioCyc; MetaCyc:HS11006-MON; -.
DR BRENDA; 1.11.1.9; 2681.
DR PathwayCommons; P18283; -.
DR Reactome; R-HSA-2142688; Synthesis of 5-eicosatetraenoic acids.
DR Reactome; R-HSA-2142712; Synthesis of 12-eicosatetraenoic acid derivatives.
DR Reactome; R-HSA-2142770; Synthesis of 15-eicosatetraenoic acid derivatives.
DR Reactome; R-HSA-3299685; Detoxification of Reactive Oxygen Species.
DR Reactome; R-HSA-5628897; TP53 Regulates Metabolic Genes.
DR SABIO-RK; P18283; -.
DR SignaLink; P18283; -.
DR BioGRID-ORCS; 2877; 26 hits in 1079 CRISPR screens.
DR ChiTaRS; GPX2; human.
DR EvolutionaryTrace; P18283; -.
DR GeneWiki; GPX2_(gene); -.
DR GenomeRNAi; 2877; -.
DR Pharos; P18283; Tbio.
DR PRO; PR:P18283; -.
DR Proteomes; UP000005640; Chromosome 14.
DR RNAct; P18283; protein.
DR Bgee; ENSG00000176153; Expressed in gall bladder and 142 other tissues.
DR ExpressionAtlas; P18283; baseline and differential.
DR Genevisible; P18283; HS.
DR GO; GO:0005737; C:cytoplasm; TAS:ProtInc.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0009055; F:electron transfer activity; TAS:UniProtKB.
DR GO; GO:0004602; F:glutathione peroxidase activity; IBA:GO_Central.
DR GO; GO:0004601; F:peroxidase activity; IBA:GO_Central.
DR GO; GO:0006979; P:response to oxidative stress; IEA:InterPro.
DR CDD; cd00340; GSH_Peroxidase; 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; PTHR11592; 1.
DR Pfam; PF00255; GSHPx; 1.
DR PIRSF; PIRSF000303; Glutathion_perox; 1.
DR PRINTS; PR01011; GLUTPROXDASE.
DR SUPFAM; SSF52833; SSF52833; 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; Cytoplasm; Oxidoreductase; Peroxidase; Reference proteome;
KW Selenocysteine.
FT CHAIN 1..190
FT /note="Glutathione peroxidase 2"
FT /id="PRO_0000066619"
FT ACT_SITE 40
FT NON_STD 40
FT /note="Selenocysteine"
FT VARIANT 37
FT /note="A -> L (requires 2 nucleotide substitutions)"
FT /evidence="ECO:0000269|PubMed:10806356"
FT /id="VAR_003615"
FT VARIANT 126
FT /note="P -> L (in dbSNP:rs17881652)"
FT /evidence="ECO:0000269|Ref.4"
FT /id="VAR_020916"
FT VARIANT 146
FT /note="R -> C (in dbSNP:rs17880492)"
FT /evidence="ECO:0000269|Ref.4"
FT /id="VAR_020917"
FT VARIANT 176
FT /note="I -> M"
FT /id="VAR_003616"
FT CONFLICT 37
FT /note="A -> R (in Ref. 1; CAB43534)"
FT /evidence="ECO:0000305"
FT CONFLICT 77
FT /note="C -> S (in Ref. 1; CAB43534)"
FT /evidence="ECO:0000305"
FT HELIX 8..10
FT /evidence="ECO:0007829|PDB:2HE3"
FT STRAND 12..15
FT /evidence="ECO:0007829|PDB:2HE3"
FT STRAND 20..22
FT /evidence="ECO:0007829|PDB:2HE3"
FT HELIX 23..26
FT /evidence="ECO:0007829|PDB:2HE3"
FT STRAND 29..36
FT /evidence="ECO:0007829|PDB:2HE3"
FT HELIX 43..56
FT /evidence="ECO:0007829|PDB:2HE3"
FT TURN 58..60
FT /evidence="ECO:0007829|PDB:2HE3"
FT STRAND 61..68
FT /evidence="ECO:0007829|PDB:2HE3"
FT HELIX 79..81
FT /evidence="ECO:0007829|PDB:2HE3"
FT HELIX 82..88
FT /evidence="ECO:0007829|PDB:2HE3"
FT STRAND 98..102
FT /evidence="ECO:0007829|PDB:2HE3"
FT STRAND 105..109
FT /evidence="ECO:0007829|PDB:2HE3"
FT HELIX 114..122
FT /evidence="ECO:0007829|PDB:2HE3"
FT HELIX 137..139
FT /evidence="ECO:0007829|PDB:2HE3"
FT STRAND 156..159
FT /evidence="ECO:0007829|PDB:2HE3"
FT STRAND 165..169
FT /evidence="ECO:0007829|PDB:2HE3"
FT HELIX 175..178
FT /evidence="ECO:0007829|PDB:2HE3"
FT HELIX 179..186
FT /evidence="ECO:0007829|PDB:2HE3"
SQ SEQUENCE 190 AA; 21954 MW; FC8C4E69C4DE83A0 CRC64;
MAFIAKSFYD LSAISLDGEK VDFNTFRGRA VLIENVASLU GTTTRDFTQL NELQCRFPRR
LVVLGFPCNQ FGHQENCQNE EILNSLKYVR PGGGYQPTFT LVQKCEVNGQ NEHPVFAYLK
DKLPYPYDDP FSLMTDPKLI IWSPVRRSDV AWNFEKFLIG PEGEPFRRYS RTFPTINIEP
DIKRLLKVAI
