GSHR_MOUSE
ID GSHR_MOUSE Reviewed; 500 AA.
AC P47791; Q7TNC2; Q8BN97; Q8C9Z6;
DT 01-FEB-1996, integrated into UniProtKB/Swiss-Prot.
DT 21-JUN-2004, sequence version 3.
DT 03-AUG-2022, entry version 200.
DE RecName: Full=Glutathione reductase, mitochondrial;
DE Short=GR;
DE Short=GRase;
DE EC=1.8.1.7;
DE Flags: Precursor;
GN Name=Gsr; Synonyms=Gr1;
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 [MRNA], AND ALTERNATIVE INITIATION.
RX PubMed=9268726; DOI=10.1006/bbrc.1997.7153;
RA Tamura T., McMicken H.W., Smith C.V., Hansen T.N.;
RT "Gene structure for mouse glutathione reductase, including a putative
RT mitochondrial targeting signal.";
RL Biochem. Biophys. Res. Commun. 237:419-422(1997).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA], AND SEQUENCE REVISION.
RA Werner D.;
RL Submitted (APR-1999) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP PARTIAL NUCLEOTIDE SEQUENCE.
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 [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Eye, and Thymus;
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 [5]
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 [6]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Brown adipose tissue, Heart, Kidney, Liver, Lung, Pancreas,
RC 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 [7]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-75, AND IDENTIFICATION BY MASS
RP 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).
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 -!- COFACTOR:
CC Name=FAD; Xref=ChEBI:CHEBI:57692; Evidence={ECO:0000250};
CC Note=Binds 1 FAD per subunit. {ECO:0000250};
CC -!- SUBUNIT: Homodimer; disulfide-linked.
CC -!- SUBCELLULAR LOCATION: [Isoform Mitochondrial]: Mitochondrion.
CC -!- SUBCELLULAR LOCATION: [Isoform Cytoplasmic]: Cytoplasm.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative initiation; Named isoforms=2;
CC Name=Mitochondrial;
CC IsoId=P47791-1; Sequence=Displayed;
CC Name=Cytoplasmic;
CC IsoId=P47791-2; Sequence=VSP_018973;
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 -!- MISCELLANEOUS: The active site is a redox-active disulfide bond.
CC -!- SIMILARITY: Belongs to the class-I pyridine nucleotide-disulfide
CC oxidoreductase family. {ECO:0000305}.
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DR EMBL; X76341; CAA53959.3; -; mRNA.
DR EMBL; AK040136; BAC30518.1; -; mRNA.
DR EMBL; AK084328; BAC39162.1; -; mRNA.
DR EMBL; BC056357; AAH56357.1; -; mRNA.
DR EMBL; BC057325; AAH57325.1; -; mRNA.
DR CCDS; CCDS22235.1; -. [P47791-1]
DR PIR; PC4370; PC4370.
DR PIR; S39494; S39494.
DR RefSeq; NP_034474.4; NM_010344.4. [P47791-1]
DR AlphaFoldDB; P47791; -.
DR SMR; P47791; -.
DR BioGRID; 200044; 7.
DR IntAct; P47791; 1.
DR MINT; P47791; -.
DR STRING; 10090.ENSMUSP00000033992; -.
DR ChEMBL; CHEMBL2366476; -.
DR iPTMnet; P47791; -.
DR PhosphoSitePlus; P47791; -.
DR SwissPalm; P47791; -.
DR EPD; P47791; -.
DR jPOST; P47791; -.
DR MaxQB; P47791; -.
DR PaxDb; P47791; -.
DR PeptideAtlas; P47791; -.
DR PRIDE; P47791; -.
DR ProteomicsDB; 271102; -. [P47791-1]
DR ProteomicsDB; 271103; -. [P47791-2]
DR Antibodypedia; 787; 452 antibodies from 36 providers.
DR DNASU; 14782; -.
DR Ensembl; ENSMUST00000033992; ENSMUSP00000033992; ENSMUSG00000031584. [P47791-1]
DR GeneID; 14782; -.
DR KEGG; mmu:14782; -.
DR UCSC; uc009lkf.1; mouse. [P47791-1]
DR CTD; 2936; -.
DR MGI; MGI:95804; Gsr.
DR VEuPathDB; HostDB:ENSMUSG00000031584; -.
DR eggNOG; KOG0405; Eukaryota.
DR GeneTree; ENSGT00940000156986; -.
DR HOGENOM; CLU_016755_2_2_1; -.
DR InParanoid; P47791; -.
DR OMA; MSKHYDY; -.
DR OrthoDB; 581771at2759; -.
DR PhylomeDB; P47791; -.
DR TreeFam; TF105353; -.
DR Reactome; R-MMU-3299685; Detoxification of Reactive Oxygen Species.
DR Reactome; R-MMU-499943; Interconversion of nucleotide di- and triphosphates.
DR Reactome; R-MMU-5628897; TP53 Regulates Metabolic Genes.
DR BioGRID-ORCS; 14782; 3 hits in 74 CRISPR screens.
DR ChiTaRS; Gsr; mouse.
DR PRO; PR:P47791; -.
DR Proteomes; UP000000589; Chromosome 8.
DR RNAct; P47791; protein.
DR Bgee; ENSMUSG00000031584; Expressed in granulocyte and 255 other tissues.
DR Genevisible; P47791; MM.
DR GO; GO:0005829; C:cytosol; ISO:MGI.
DR GO; GO:0009897; C:external side of plasma membrane; IDA:MGI.
DR GO; GO:0005739; C:mitochondrion; HDA:MGI.
DR GO; GO:0050660; F:flavin adenine dinucleotide binding; ISO:MGI.
DR GO; GO:0043295; F:glutathione binding; ISO:MGI.
DR GO; GO:0004362; F:glutathione-disulfide reductase (NADPH) activity; IDA:MGI.
DR GO; GO:0042802; F:identical protein binding; ISO:MGI.
DR GO; GO:0050661; F:NADP binding; ISO:MGI.
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; ISO:MGI.
DR GO; GO:0007283; P:spermatogenesis; ISO:MGI.
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 Acetylation; Alternative initiation; Cytoplasm; Disulfide bond; FAD;
KW Flavoprotein; Mitochondrion; NADP; Oxidoreductase; Redox-active center;
KW Reference proteome; Transit peptide.
FT TRANSIT 1..26
FT /note="Mitochondrion"
FT /evidence="ECO:0000255"
FT CHAIN 27..500
FT /note="Glutathione reductase, mitochondrial"
FT /id="PRO_0000030278"
FT ACT_SITE 489
FT /note="Proton acceptor"
FT /evidence="ECO:0000250"
FT BINDING 72..80
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250"
FT MOD_RES 75
FT /note="N6-acetyllysine"
FT /evidence="ECO:0007744|PubMed:23576753"
FT DISULFID 80..85
FT /note="Redox-active"
FT /evidence="ECO:0000250"
FT DISULFID 112
FT /note="Interchain"
FT /evidence="ECO:0000250"
FT VAR_SEQ 1..26
FT /note="Missing (in isoform Cytoplasmic)"
FT /evidence="ECO:0000305"
FT /id="VSP_018973"
FT CONFLICT 26
FT /note="A -> T (in Ref. 2; CAA53959)"
FT /evidence="ECO:0000305"
FT CONFLICT 255
FT /note="N -> K (in Ref. 2; CAA53959)"
FT /evidence="ECO:0000305"
FT CONFLICT 300
FT /note="M -> V (in Ref. 2; CAA53959)"
FT /evidence="ECO:0000305"
FT CONFLICT 312
FT /note="G -> R (in Ref. 5; AAH56357/AAH57325)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 500 AA; 53663 MW; A2E6F629B5CC0B7B CRC64;
MALLPRALGV GAAPSLRRAA RALTCAMASP GEPQPPAPDT SSFDYLVIGG GSGGLASARR
AAELGARAAV VESHKLGGTC VNVGCVPKKV MWNTAVHSEF MHDHVDYGFQ SCEGKFSWHV
IKQKRDAYVS RLNTIYQNNL TKSHIEIIHG YATFADGPRP TVEVNGKKFT APHILIATGG
VPTVPHESQI PGASLGITSD GFFQLEDLPS RSVIVGAGYI AVEIAGILSA LGSKTSLMIR
HDKVLRNFDS LISSNCTEEL ENAGVEVLKF TQVKEVKKTS SGLELQVVTS VPGRKPTTTM
IPDVDCLLWA IGRDPNSKGL NLNKVGIQTD EKGHILVDEF QNTNVKGVYA VGDVCGKALL
TPVAIAAGRK LAHRLFECKQ DSKLDYDNIP TVVFSHPPIG TVGLTEDEAV HKYGKDNVKI
YSTAFTPMYH AVTTRKTKCV MKMVCANKEE KVVGIHMQGI GCDEMLQGFA VAVKMGATKA
DFDNTVAIHP TSSEELVTLR
