GSHR_HUMAN
ID GSHR_HUMAN Reviewed; 522 AA.
AC P00390; C8KIL8; C8KIL9; C8KIM0; D3DSV3; Q7Z5C9; Q9NP63;
DT 21-JUL-1986, integrated into UniProtKB/Swiss-Prot.
DT 11-JUL-2001, sequence version 2.
DT 03-AUG-2022, entry version 254.
DE RecName: Full=Glutathione reductase, mitochondrial;
DE Short=GR;
DE Short=GRase;
DE EC=1.8.1.7 {ECO:0000269|PubMed:17185460};
DE Flags: Precursor;
GN Name=GSR; Synonyms=GLUR, GRD1;
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] (ISOFORM CYTOPLASMIC).
RC TISSUE=Placenta;
RX PubMed=2185014; DOI=10.1111/j.1432-1033.1990.tb15431.x;
RA Tutic M., Lu X.A., Schirmer R.H., Werner D.;
RT "Cloning and sequencing of mammalian glutathione reductase cDNA.";
RL Eur. J. Biochem. 188:523-528(1990).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORM MITOCHONDRIAL), AND
RP ALTERNATIVE INITIATION.
RX PubMed=10708558; DOI=10.1006/bbrc.2000.2267;
RA Kelner M.J., Montoya M.A.;
RT "Structural organization of the human glutathione reductase (GSR) gene:
RT determination of correct cDNA sequence and identification of a
RT mitochondrial leader sequence.";
RL Biochem. Biophys. Res. Commun. 269:366-368(2000).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS CYS-153; SER-232; VAL-261
RP AND ASP-297.
RG NIEHS SNPs program;
RL Submitted (JUL-2003) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 2; 3 AND 4), ALTERNATIVE SPLICING, AND
RP TISSUE SPECIFICITY.
RX PubMed=20628807; DOI=10.1007/s10528-010-9362-z;
RA Satoh N., Watanabe N., Kanda A., Sugaya-Fukazawa M., Hisatomi H.;
RT "Expression of glutathione reductase splice variants in human tissues.";
RL Biochem. Genet. 48:816-821(2010).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16421571; DOI=10.1038/nature04406;
RA Nusbaum C., Mikkelsen T.S., Zody M.C., Asakawa S., Taudien S., Garber M.,
RA Kodira C.D., Schueler M.G., Shimizu A., Whittaker C.A., Chang J.L.,
RA Cuomo C.A., Dewar K., FitzGerald M.G., Yang X., Allen N.R., Anderson S.,
RA Asakawa T., Blechschmidt K., Bloom T., Borowsky M.L., Butler J., Cook A.,
RA Corum B., DeArellano K., DeCaprio D., Dooley K.T., Dorris L. III,
RA Engels R., Gloeckner G., Hafez N., Hagopian D.S., Hall J.L., Ishikawa S.K.,
RA Jaffe D.B., Kamat A., Kudoh J., Lehmann R., Lokitsang T., Macdonald P.,
RA Major J.E., Matthews C.D., Mauceli E., Menzel U., Mihalev A.H.,
RA Minoshima S., Murayama Y., Naylor J.W., Nicol R., Nguyen C., O'Leary S.B.,
RA O'Neill K., Parker S.C.J., Polley A., Raymond C.K., Reichwald K.,
RA Rodriguez J., Sasaki T., Schilhabel M., Siddiqui R., Smith C.L.,
RA Sneddon T.P., Talamas J.A., Tenzin P., Topham K., Venkataraman V., Wen G.,
RA Yamazaki S., Young S.K., Zeng Q., Zimmer A.R., Rosenthal A., Birren B.W.,
RA Platzer M., Shimizu N., Lander E.S.;
RT "DNA sequence and analysis of human chromosome 8.";
RL Nature 439:331-335(2006).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM MITOCHONDRIAL).
RC TISSUE=Lung;
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 [8]
RP PROTEIN SEQUENCE OF 45-522.
RX PubMed=7060551; DOI=10.1111/j.1432-1033.1982.tb05780.x;
RA Krauth-Siegel R.L., Blatterspiel R., Saleh M., Schiltz E., Schirmer R.H.,
RA Untucht-Grau R.;
RT "Glutathione reductase from human erythrocytes. The sequences of the NADPH
RT domain and of the interface domain.";
RL Eur. J. Biochem. 121:259-267(1982).
RN [9]
RP PROTEIN SEQUENCE OF 98-110.
RC TISSUE=Erythrocyte;
RX PubMed=923580; DOI=10.1111/j.1432-1033.1977.tb11856.x;
RA Krohne-Ehrich G., Schirmer R.H., Untucht-Grau R.;
RT "Glutathione reductase from human erythrocytes. Isolation of the enzyme and
RT sequence analysis of the redox-active peptide.";
RL Eur. J. Biochem. 80:65-71(1977).
RN [10]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=15592455; DOI=10.1038/nbt1046;
RA Rush J., Moritz A., Lee K.A., Guo A., Goss V.L., Spek E.J., Zhang H.,
RA Zha X.-M., Polakiewicz R.D., Comb M.J.;
RT "Immunoaffinity profiling of tyrosine phosphorylation in cancer cells.";
RL Nat. Biotechnol. 23:94-101(2005).
RN [11]
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 [12]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Erythroleukemia;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [13]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [14]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=25944712; DOI=10.1002/pmic.201400617;
RA Vaca Jacome A.S., Rabilloud T., Schaeffer-Reiss C., Rompais M., Ayoub D.,
RA Lane L., Bairoch A., Van Dorsselaer A., Carapito C.;
RT "N-terminome analysis of the human mitochondrial proteome.";
RL Proteomics 15:2519-2524(2015).
RN [15]
RP INVOLVEMENT IN HAGRD, CATALYTIC ACTIVITY, VARIANTS HAGRD 331-TRP--ARG-522
RP DEL AND ALA-374, AND CHARACTERIZATION OF VARIANT HAGRD ALA-374.
RX PubMed=17185460; DOI=10.1182/blood-2006-08-042531;
RA Kamerbeek N.M., van Zwieten R., de Boer M., Morren G., Vuil H., Bannink N.,
RA Lincke C., Dolman K.M., Becker K., Schirmer R.H., Gromer S., Roos D.;
RT "Molecular basis of glutathione reductase deficiency in human blood
RT cells.";
RL Blood 109:3560-3566(2007).
RN [16]
RP X-RAY CRYSTALLOGRAPHY (2 ANGSTROMS) OF 45-522.
RX PubMed=7334521; DOI=10.1016/0022-2836(81)90126-1;
RA Thieme R., Pai E.F., Schirmer R.H., Schulz G.E.;
RT "Three-dimensional structure of glutathione reductase at 2-A resolution.";
RL J. Mol. Biol. 152:763-782(1981).
RN [17]
RP X-RAY CRYSTALLOGRAPHY (1.57 ANGSTROMS) OF 45-522.
RX PubMed=3656429; DOI=10.1016/0022-2836(87)90191-4;
RA Karplus P.A., Schulz G.E.;
RT "Refined structure of glutathione reductase at 1.54-A resolution.";
RL J. Mol. Biol. 195:701-729(1987).
RN [18]
RP X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 62-522, AND DISULFIDE BONDS.
RX PubMed=8626496; DOI=10.1074/jbc.271.14.8101;
RA Savvides S.N., Karplus P.A.;
RT "Kinetics and crystallographic analysis of human glutathione reductase in
RT complex with a xanthene inhibitor.";
RL J. Biol. Chem. 271:8101-8107(1996).
RN [19]
RP X-RAY CRYSTALLOGRAPHY (2.4 ANGSTROMS) OF 62-522.
RX PubMed=9174360; DOI=10.1021/bi963074p;
RA Stoll V.S., Simpson S.J., Krauth-Siegel R.L., Walsh C.T., Pai E.F.;
RT "Glutathione reductase turned into trypanothione reductase: structural
RT analysis of an engineered change in substrate specificity.";
RL Biochemistry 36:6437-6447(1997).
RN [20]
RP X-RAY CRYSTALLOGRAPHY (1.7 ANGSTROMS) OF 62-522.
RX PubMed=9546215; DOI=10.1038/nsb0498-267;
RA Becker K., Savvides S.N., Keese M., Schirmer R.H., Karplus P.A.;
RT "Enzyme inactivation through sulfhydryl oxidation by physiologic NO-
RT carriers.";
RL Nat. Struct. Biol. 5:267-271(1998).
CC -!- FUNCTION: Maintains high levels of reduced glutathione in the cytosol.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=2 glutathione + NADP(+) = glutathione disulfide + H(+) +
CC NADPH; Xref=Rhea:RHEA:11740, ChEBI:CHEBI:15378, ChEBI:CHEBI:57783,
CC ChEBI:CHEBI:57925, ChEBI:CHEBI:58297, ChEBI:CHEBI:58349; EC=1.8.1.7;
CC Evidence={ECO:0000269|PubMed:17185460};
CC -!- COFACTOR:
CC Name=FAD; Xref=ChEBI:CHEBI:57692;
CC Note=Binds 1 FAD per subunit.;
CC -!- SUBUNIT: Homodimer; disulfide-linked. {ECO:0000269|PubMed:8626496}.
CC -!- SUBCELLULAR LOCATION: [Isoform Mitochondrial]: Mitochondrion.
CC -!- SUBCELLULAR LOCATION: [Isoform Cytoplasmic]: Cytoplasm.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing, Alternative initiation; Named isoforms=5;
CC Name=Mitochondrial;
CC IsoId=P00390-1; Sequence=Displayed;
CC Name=Cytoplasmic;
CC IsoId=P00390-2; Sequence=VSP_018972;
CC Name=2; Synonyms=delta8;
CC IsoId=P00390-3; Sequence=VSP_042908;
CC Name=3; Synonyms=delta9;
CC IsoId=P00390-4; Sequence=VSP_042909;
CC Name=4; Synonyms=delta8+9;
CC IsoId=P00390-5; Sequence=VSP_042908, VSP_042909;
CC -!- DOMAIN: Each subunit can be divided into 4 domains that are consecutive
CC along the polypeptide chain. Domains 1 and 2 bind FAD and NADPH,
CC respectively. Domain 4 forms the interface.
CC -!- DISEASE: Hemolytic anemia due to glutathione reductase deficiency
CC (HAGRD) [MIM:618660]: An autosomal recessive disease characterized by
CC hemolytic anemia and impaired activity of glutathione reductase.
CC Patients experience hemolytic anemia in response to oxidative stress or
CC ingestion of fava beans. {ECO:0000269|PubMed:17185460}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
CC -!- MISCELLANEOUS: The active site is a redox-active disulfide bond.
CC -!- MISCELLANEOUS: [Isoform Cytoplasmic]: Produced by alternative
CC initiation of isoform Mitochondrial. {ECO:0000305}.
CC -!- MISCELLANEOUS: [Isoform 3]: Expressed at very high levels in peripheral
CC blood. {ECO:0000305}.
CC -!- SIMILARITY: Belongs to the class-I pyridine nucleotide-disulfide
CC oxidoreductase family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAP88037.1; Type=Erroneous initiation; Evidence={ECO:0000305};
CC -!- WEB RESOURCE: Name=NIEHS-SNPs;
CC URL="http://egp.gs.washington.edu/data/gsr/";
CC -!- WEB RESOURCE: Name=Wikipedia; Note=Glutathione reductase entry;
CC URL="https://en.wikipedia.org/wiki/Glutathione_reductase";
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DR EMBL; X15722; CAA33744.1; -; mRNA.
DR EMBL; AF228703; AAF37572.1; -; Genomic_DNA.
DR EMBL; AF228703; AAF37573.1; -; Genomic_DNA.
DR EMBL; AF228704; AAF37574.1; -; mRNA.
DR EMBL; AY338490; AAP88037.1; ALT_INIT; Genomic_DNA.
DR EMBL; AB519179; BAI43437.1; -; mRNA.
DR EMBL; AB519180; BAI43438.1; -; mRNA.
DR EMBL; AB519181; BAI43439.1; -; mRNA.
DR EMBL; AC009314; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC103959; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AF215848; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471080; EAW63443.1; -; Genomic_DNA.
DR EMBL; CH471080; EAW63445.1; -; Genomic_DNA.
DR EMBL; BC069244; AAH69244.1; -; mRNA.
DR CCDS; CCDS34877.1; -. [P00390-1]
DR CCDS; CCDS56530.1; -. [P00390-5]
DR CCDS; CCDS56531.1; -. [P00390-3]
DR CCDS; CCDS56532.1; -. [P00390-4]
DR PIR; S08979; RDHUU.
DR RefSeq; NP_000628.2; NM_000637.3. [P00390-1]
DR RefSeq; NP_001182031.1; NM_001195102.1. [P00390-3]
DR RefSeq; NP_001182032.1; NM_001195103.1. [P00390-4]
DR RefSeq; NP_001182033.1; NM_001195104.1. [P00390-5]
DR PDB; 1ALG; NMR; -; A=480-503.
DR PDB; 1BWC; X-ray; 2.10 A; A=45-522.
DR PDB; 1DNC; X-ray; 1.70 A; A=45-522.
DR PDB; 1GRA; X-ray; 2.00 A; A=45-522.
DR PDB; 1GRB; X-ray; 1.85 A; A=45-522.
DR PDB; 1GRE; X-ray; 2.00 A; A=45-522.
DR PDB; 1GRF; X-ray; 2.00 A; A=45-522.
DR PDB; 1GRG; X-ray; 2.00 A; A=45-522.
DR PDB; 1GRH; X-ray; 3.00 A; A=45-522.
DR PDB; 1GRT; X-ray; 2.30 A; A=45-522.
DR PDB; 1GSN; X-ray; 1.70 A; A=45-522.
DR PDB; 1K4Q; X-ray; 1.90 A; A=62-522.
DR PDB; 1XAN; X-ray; 2.00 A; A=62-522.
DR PDB; 2AAQ; X-ray; 2.60 A; A=44-522.
DR PDB; 2GH5; X-ray; 1.70 A; A/B=45-522.
DR PDB; 2GRT; X-ray; 2.70 A; A=62-522.
DR PDB; 3DJG; X-ray; 1.80 A; X=45-522.
DR PDB; 3DJJ; X-ray; 1.10 A; A=45-522.
DR PDB; 3DK4; X-ray; 1.20 A; A=45-522.
DR PDB; 3DK8; X-ray; 1.10 A; A=45-522.
DR PDB; 3DK9; X-ray; 0.95 A; A=45-522.
DR PDB; 3GRS; X-ray; 1.54 A; A=45-522.
DR PDB; 3GRT; X-ray; 2.50 A; A=62-522.
DR PDB; 3SQP; X-ray; 2.21 A; A/B=45-522.
DR PDB; 4GR1; X-ray; 2.40 A; A=45-522.
DR PDB; 4GRT; X-ray; 2.80 A; A=62-522.
DR PDB; 5GRT; X-ray; 2.40 A; A=62-522.
DR PDBsum; 1ALG; -.
DR PDBsum; 1BWC; -.
DR PDBsum; 1DNC; -.
DR PDBsum; 1GRA; -.
DR PDBsum; 1GRB; -.
DR PDBsum; 1GRE; -.
DR PDBsum; 1GRF; -.
DR PDBsum; 1GRG; -.
DR PDBsum; 1GRH; -.
DR PDBsum; 1GRT; -.
DR PDBsum; 1GSN; -.
DR PDBsum; 1K4Q; -.
DR PDBsum; 1XAN; -.
DR PDBsum; 2AAQ; -.
DR PDBsum; 2GH5; -.
DR PDBsum; 2GRT; -.
DR PDBsum; 3DJG; -.
DR PDBsum; 3DJJ; -.
DR PDBsum; 3DK4; -.
DR PDBsum; 3DK8; -.
DR PDBsum; 3DK9; -.
DR PDBsum; 3GRS; -.
DR PDBsum; 3GRT; -.
DR PDBsum; 3SQP; -.
DR PDBsum; 4GR1; -.
DR PDBsum; 4GRT; -.
DR PDBsum; 5GRT; -.
DR AlphaFoldDB; P00390; -.
DR SMR; P00390; -.
DR BioGRID; 109191; 79.
DR IntAct; P00390; 9.
DR MINT; P00390; -.
DR STRING; 9606.ENSP00000221130; -.
DR BindingDB; P00390; -.
DR ChEMBL; CHEMBL2755; -.
DR DrugBank; DB07393; 2-(2-PHENYL-3-PYRIDIN-2-YL-4,5,6,7-TETRAHYDRO-2H-ISOPHOSPHINDOL-1-YL)PYRIDINE.
DR DrugBank; DB01644; 3,6-dihydroxy-xanthene-9-propionic acid.
DR DrugBank; DB02895; 3-(Prop-2-Ene-1-Sulfinyl)-Propene-1-Thiol.
DR DrugBank; DB03867; 3-nitro-L-tyrosine.
DR DrugBank; DB02153; 3-sulfino-L-alanine.
DR DrugBank; DB07714; 6-(3-METHYL-1,4-DIOXO-1,4-DIHYDRONAPHTHALEN-2-YL)HEXANOIC ACID.
DR DrugBank; DB09061; Cannabidiol.
DR DrugBank; DB00262; Carmustine.
DR DrugBank; DB09130; Copper.
DR DrugBank; DB03147; Flavin adenine dinucleotide.
DR DrugBank; DB00143; Glutathione.
DR DrugBank; DB03310; Glutathione disulfide.
DR DrugBank; DB02553; Glutathionylspermidine disulfide.
DR DrugBank; DB14009; Medical Cannabis.
DR DrugBank; DB14011; Nabiximols.
DR DrugBank; DB00157; NADH.
DR DrugBank; DB11135; Selenium.
DR DrugBank; DB11590; Thimerosal.
DR DrugCentral; P00390; -.
DR CarbonylDB; P00390; -.
DR GlyGen; P00390; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; P00390; -.
DR PhosphoSitePlus; P00390; -.
DR BioMuta; GSR; -.
DR DMDM; 14916998; -.
DR REPRODUCTION-2DPAGE; IPI00759575; -.
DR EPD; P00390; -.
DR jPOST; P00390; -.
DR MassIVE; P00390; -.
DR MaxQB; P00390; -.
DR PaxDb; P00390; -.
DR PeptideAtlas; P00390; -.
DR PRIDE; P00390; -.
DR ProteomicsDB; 51241; -. [P00390-1]
DR ProteomicsDB; 51242; -. [P00390-2]
DR ProteomicsDB; 51243; -. [P00390-3]
DR ProteomicsDB; 51244; -. [P00390-4]
DR ProteomicsDB; 51245; -. [P00390-5]
DR Antibodypedia; 787; 452 antibodies from 36 providers.
DR DNASU; 2936; -.
DR Ensembl; ENST00000221130.11; ENSP00000221130.5; ENSG00000104687.14. [P00390-1]
DR Ensembl; ENST00000537535.5; ENSP00000438845.1; ENSG00000104687.14. [P00390-5]
DR Ensembl; ENST00000541648.5; ENSP00000444559.1; ENSG00000104687.14. [P00390-4]
DR Ensembl; ENST00000546342.5; ENSP00000445516.1; ENSG00000104687.14. [P00390-3]
DR GeneID; 2936; -.
DR KEGG; hsa:2936; -.
DR MANE-Select; ENST00000221130.11; ENSP00000221130.5; NM_000637.5; NP_000628.2.
DR UCSC; uc022ato.2; human. [P00390-1]
DR CTD; 2936; -.
DR DisGeNET; 2936; -.
DR GeneCards; GSR; -.
DR HGNC; HGNC:4623; GSR.
DR HPA; ENSG00000104687; Low tissue specificity.
DR MalaCards; GSR; -.
DR MIM; 138300; gene.
DR MIM; 618660; phenotype.
DR neXtProt; NX_P00390; -.
DR OpenTargets; ENSG00000104687; -.
DR Orphanet; 90030; Hemolytic anemia due to glutathione reductase deficiency.
DR PharmGKB; PA29014; -.
DR VEuPathDB; HostDB:ENSG00000104687; -.
DR eggNOG; KOG0405; Eukaryota.
DR GeneTree; ENSGT00940000156986; -.
DR HOGENOM; CLU_016755_2_2_1; -.
DR InParanoid; P00390; -.
DR OMA; MSKHYDY; -.
DR PhylomeDB; P00390; -.
DR TreeFam; TF105353; -.
DR BioCyc; MetaCyc:HS02602-MON; -.
DR BRENDA; 1.8.1.7; 2681.
DR PathwayCommons; P00390; -.
DR Reactome; R-HSA-2408550; Metabolism of ingested H2SeO4 and H2SeO3 into H2Se. [P00390-2]
DR Reactome; R-HSA-3299685; Detoxification of Reactive Oxygen Species.
DR Reactome; R-HSA-499943; Interconversion of nucleotide di- and triphosphates. [P00390-2]
DR Reactome; R-HSA-5628897; TP53 Regulates Metabolic Genes. [P00390-2]
DR Reactome; R-HSA-9759194; Nuclear events mediated by NFE2L2. [P00390-2]
DR SABIO-RK; P00390; -.
DR SignaLink; P00390; -.
DR BioGRID-ORCS; 2936; 12 hits in 1081 CRISPR screens.
DR ChiTaRS; GSR; human.
DR EvolutionaryTrace; P00390; -.
DR GeneWiki; Glutathione_reductase; -.
DR GenomeRNAi; 2936; -.
DR Pharos; P00390; Tclin.
DR PRO; PR:P00390; -.
DR Proteomes; UP000005640; Chromosome 8.
DR RNAct; P00390; protein.
DR Bgee; ENSG00000104687; Expressed in pylorus and 191 other tissues.
DR ExpressionAtlas; P00390; baseline and differential.
DR Genevisible; P00390; HS.
DR GO; GO:0005829; C:cytosol; IDA:HPA.
DR GO; GO:0009897; C:external side of plasma membrane; IEA:Ensembl.
DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR GO; GO:0005759; C:mitochondrial matrix; TAS:Reactome.
DR GO; GO:0005739; C:mitochondrion; IBA:GO_Central.
DR GO; GO:0009055; F:electron transfer activity; TAS:UniProtKB.
DR GO; GO:0050660; F:flavin adenine dinucleotide binding; IBA:GO_Central.
DR GO; GO:0004362; F:glutathione-disulfide reductase (NADPH) activity; IBA:GO_Central.
DR GO; GO:0050661; F:NADP binding; IEA:InterPro.
DR GO; GO:0045454; P:cell redox homeostasis; IBA:GO_Central.
DR GO; GO:0034599; P:cellular response to oxidative stress; IBA:GO_Central.
DR GO; GO:0006749; P:glutathione metabolic process; IBA:GO_Central.
DR Gene3D; 3.30.390.30; -; 1.
DR Gene3D; 3.50.50.60; -; 2.
DR InterPro; IPR036188; FAD/NAD-bd_sf.
DR InterPro; IPR023753; FAD/NAD-binding_dom.
DR InterPro; IPR016156; FAD/NAD-linked_Rdtase_dimer_sf.
DR InterPro; IPR006322; Glutathione_Rdtase_euk/bac.
DR InterPro; IPR001100; Pyr_nuc-diS_OxRdtase.
DR InterPro; IPR004099; Pyr_nucl-diS_OxRdtase_dimer.
DR InterPro; IPR012999; Pyr_OxRdtase_I_AS.
DR PANTHER; PTHR42737; PTHR42737; 1.
DR Pfam; PF07992; Pyr_redox_2; 1.
DR Pfam; PF02852; Pyr_redox_dim; 1.
DR PIRSF; PIRSF000350; Mercury_reductase_MerA; 1.
DR SUPFAM; SSF51905; SSF51905; 1.
DR SUPFAM; SSF55424; SSF55424; 1.
DR TIGRFAMs; TIGR01421; gluta_reduc_1; 1.
DR PROSITE; PS00076; PYRIDINE_REDOX_1; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Alternative initiation; Alternative splicing;
KW Cytoplasm; Direct protein sequencing; Disease variant; Disulfide bond; FAD;
KW Flavoprotein; Hereditary hemolytic anemia; Mitochondrion; NADP;
KW Oxidoreductase; Redox-active center; Reference proteome; Transit peptide.
FT TRANSIT 1..43
FT /note="Mitochondrion"
FT /evidence="ECO:0000255"
FT CHAIN 44..522
FT /note="Glutathione reductase, mitochondrial"
FT /id="PRO_0000030276"
FT ACT_SITE 511
FT /note="Proton acceptor"
FT BINDING 94..102
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT MOD_RES 97
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P47791"
FT DISULFID 102..107
FT /note="Redox-active"
FT /evidence="ECO:0000269|PubMed:8626496"
FT DISULFID 134
FT /note="Interchain"
FT /evidence="ECO:0000269|PubMed:8626496"
FT VAR_SEQ 1..43
FT /note="Missing (in isoform Cytoplasmic)"
FT /evidence="ECO:0000303|PubMed:2185014"
FT /id="VSP_018972"
FT VAR_SEQ 266..294
FT /note="Missing (in isoform 2 and isoform 4)"
FT /evidence="ECO:0000303|PubMed:20628807"
FT /id="VSP_042908"
FT VAR_SEQ 295..347
FT /note="Missing (in isoform 3 and isoform 4)"
FT /evidence="ECO:0000303|PubMed:20628807"
FT /id="VSP_042909"
FT VARIANT 153
FT /note="R -> C (in dbSNP:rs8190955)"
FT /evidence="ECO:0000269|Ref.3"
FT /id="VAR_019079"
FT VARIANT 232
FT /note="G -> R (in dbSNP:rs8190976)"
FT /id="VAR_051775"
FT VARIANT 232
FT /note="G -> S (in dbSNP:rs8190976)"
FT /evidence="ECO:0000269|Ref.3"
FT /id="VAR_019080"
FT VARIANT 261
FT /note="I -> V (in dbSNP:rs8190997)"
FT /evidence="ECO:0000269|Ref.3"
FT /id="VAR_019081"
FT VARIANT 297
FT /note="E -> D (in dbSNP:rs8191004)"
FT /evidence="ECO:0000269|Ref.3"
FT /id="VAR_019082"
FT VARIANT 314
FT /note="P -> H (in dbSNP:rs2020916)"
FT /id="VAR_014554"
FT VARIANT 331..522
FT /note="Missing (in HAGRD)"
FT /evidence="ECO:0000269|PubMed:17185460"
FT /id="VAR_083444"
FT VARIANT 374
FT /note="G -> A (in HAGRD; decreased glutathione reductase
FT activity; decreased enzyme stability; dbSNP:rs1586033745)"
FT /evidence="ECO:0000269|PubMed:17185460"
FT /id="VAR_083445"
FT STRAND 62..64
FT /evidence="ECO:0007829|PDB:3DK9"
FT STRAND 66..70
FT /evidence="ECO:0007829|PDB:3DK9"
FT HELIX 74..85
FT /evidence="ECO:0007829|PDB:3DK9"
FT STRAND 90..96
FT /evidence="ECO:0007829|PDB:3DK9"
FT HELIX 100..105
FT /evidence="ECO:0007829|PDB:3DK9"
FT HELIX 107..123
FT /evidence="ECO:0007829|PDB:3DK9"
FT TURN 124..130
FT /evidence="ECO:0007829|PDB:3DK9"
FT HELIX 140..164
FT /evidence="ECO:0007829|PDB:3DK9"
FT STRAND 168..172
FT /evidence="ECO:0007829|PDB:3DK9"
FT STRAND 174..176
FT /evidence="ECO:0007829|PDB:3DK9"
FT STRAND 183..186
FT /evidence="ECO:0007829|PDB:3DK9"
FT STRAND 189..192
FT /evidence="ECO:0007829|PDB:3DK9"
FT STRAND 196..198
FT /evidence="ECO:0007829|PDB:3DK9"
FT STRAND 202..204
FT /evidence="ECO:0007829|PDB:3DK9"
FT TURN 209..211
FT /evidence="ECO:0007829|PDB:3DK9"
FT HELIX 215..217
FT /evidence="ECO:0007829|PDB:3DK9"
FT HELIX 221..224
FT /evidence="ECO:0007829|PDB:3DK9"
FT STRAND 232..237
FT /evidence="ECO:0007829|PDB:3DK9"
FT HELIX 241..252
FT /evidence="ECO:0007829|PDB:3DK9"
FT STRAND 256..260
FT /evidence="ECO:0007829|PDB:3DK9"
FT STRAND 262..266
FT /evidence="ECO:0007829|PDB:3DK9"
FT HELIX 272..284
FT /evidence="ECO:0007829|PDB:3DK9"
FT STRAND 288..290
FT /evidence="ECO:0007829|PDB:3DK9"
FT STRAND 293..300
FT /evidence="ECO:0007829|PDB:3DK9"
FT STRAND 302..311
FT /evidence="ECO:0007829|PDB:3DK9"
FT STRAND 319..331
FT /evidence="ECO:0007829|PDB:3DK9"
FT STRAND 335..338
FT /evidence="ECO:0007829|PDB:3DK9"
FT TURN 340..343
FT /evidence="ECO:0007829|PDB:3GRS"
FT HELIX 344..347
FT /evidence="ECO:0007829|PDB:3DK9"
FT STRAND 370..372
FT /evidence="ECO:0007829|PDB:3DK9"
FT HELIX 374..377
FT /evidence="ECO:0007829|PDB:3DK9"
FT HELIX 383..398
FT /evidence="ECO:0007829|PDB:3DK9"
FT STRAND 413..415
FT /evidence="ECO:0007829|PDB:3DK9"
FT STRAND 417..419
FT /evidence="ECO:0007829|PDB:1GSN"
FT STRAND 421..425
FT /evidence="ECO:0007829|PDB:3DK9"
FT HELIX 428..435
FT /evidence="ECO:0007829|PDB:3DK9"
FT HELIX 437..439
FT /evidence="ECO:0007829|PDB:3DK9"
FT STRAND 440..447
FT /evidence="ECO:0007829|PDB:3DK9"
FT HELIX 450..454
FT /evidence="ECO:0007829|PDB:3DK9"
FT STRAND 461..468
FT /evidence="ECO:0007829|PDB:3DK9"
FT TURN 469..472
FT /evidence="ECO:0007829|PDB:3DK9"
FT STRAND 473..481
FT /evidence="ECO:0007829|PDB:3DK9"
FT HELIX 484..496
FT /evidence="ECO:0007829|PDB:3DK9"
FT HELIX 501..505
FT /evidence="ECO:0007829|PDB:3DK9"
FT STRAND 511..514
FT /evidence="ECO:0007829|PDB:3DK9"
FT HELIX 515..519
FT /evidence="ECO:0007829|PDB:3DK9"
SQ SEQUENCE 522 AA; 56257 MW; DD8E2BA9D6E3757B CRC64;
MALLPRALSA GAGPSWRRAA RAFRGFLLLL PEPAALTRAL SRAMACRQEP QPQGPPPAAG
AVASYDYLVI GGGSGGLASA RRAAELGARA AVVESHKLGG TCVNVGCVPK KVMWNTAVHS
EFMHDHADYG FPSCEGKFNW RVIKEKRDAY VSRLNAIYQN NLTKSHIEII RGHAAFTSDP
KPTIEVSGKK YTAPHILIAT GGMPSTPHES QIPGASLGIT SDGFFQLEEL PGRSVIVGAG
YIAVEMAGIL SALGSKTSLM IRHDKVLRSF DSMISTNCTE ELENAGVEVL KFSQVKEVKK
TLSGLEVSMV TAVPGRLPVM TMIPDVDCLL WAIGRVPNTK DLSLNKLGIQ TDDKGHIIVD
EFQNTNVKGI YAVGDVCGKA LLTPVAIAAG RKLAHRLFEY KEDSKLDYNN IPTVVFSHPP
IGTVGLTEDE AIHKYGIENV KTYSTSFTPM YHAVTKRKTK CVMKMVCANK EEKVVGIHMQ
GLGCDEMLQG FAVAVKMGAT KADFDNTVAI HPTSSEELVT LR
