GSHR_CAEEL
ID GSHR_CAEEL Reviewed; 473 AA.
AC Q93379; Q86DB5;
DT 08-JUN-2016, integrated into UniProtKB/Swiss-Prot.
DT 01-AUG-1998, sequence version 2.
DT 03-AUG-2022, entry version 167.
DE RecName: Full=Glutathione reductase, mitochondrial {ECO:0000250|UniProtKB:P00390};
DE Short=GR {ECO:0000250|UniProtKB:P00390};
DE EC=1.8.1.7 {ECO:0000269|PubMed:23593298};
DE AltName: Full=Glutathione disulfide reductase {ECO:0000312|WormBase:C46F11.2a};
DE Flags: Precursor;
GN Name=gsr-1 {ECO:0000312|WormBase:C46F11.2a};
GN ORFNames=C46F11.2 {ECO:0000312|WormBase:C46F11.2a};
OS Caenorhabditis elegans.
OC Eukaryota; Metazoa; Ecdysozoa; Nematoda; Chromadorea; Rhabditida;
OC Rhabditina; Rhabditomorpha; Rhabditoidea; Rhabditidae; Peloderinae;
OC Caenorhabditis.
OX NCBI_TaxID=6239 {ECO:0000312|Proteomes:UP000001940};
RN [1] {ECO:0000312|Proteomes:UP000001940}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Bristol N2 {ECO:0000312|Proteomes:UP000001940};
RX PubMed=9851916; DOI=10.1126/science.282.5396.2012;
RG The C. elegans sequencing consortium;
RT "Genome sequence of the nematode C. elegans: a platform for investigating
RT biology.";
RL Science 282:2012-2018(1998).
RN [2] {ECO:0000305}
RP FUNCTION, TISSUE SPECIFICITY, AND DISRUPTION PHENOTYPE.
RX PubMed=21199936; DOI=10.1073/pnas.1006328108;
RA Stenvall J., Fierro-Gonzalez J.C., Swoboda P., Saamarthy K., Cheng Q.,
RA Cacho-Valadez B., Arner E.S., Persson O.P., Miranda-Vizuete A., Tuck S.;
RT "Selenoprotein TRXR-1 and GSR-1 are essential for removal of old cuticle
RT during molting in Caenorhabditis elegans.";
RL Proc. Natl. Acad. Sci. U.S.A. 108:1064-1069(2011).
RN [3] {ECO:0000305}
RP FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, TISSUE
RP SPECIFICITY, INDUCTION BY STARVATION AND JUGLONE, AND DISRUPTION PHENOTYPE.
RX PubMed=23593298; DOI=10.1371/journal.pone.0060731;
RA Lueersen K., Stegehake D., Daniel J., Drescher M., Ajonina I., Ajonina C.,
RA Hertel P., Woltersdorf C., Liebau E.;
RT "The glutathione reductase GSR-1 determines stress tolerance and longevity
RT in Caenorhabditis elegans.";
RL PLoS ONE 8:E60731-E60731(2013).
CC -!- FUNCTION: Maintains high levels of reduced glutathione in the cytosol
CC (PubMed:23593298). Involved in resistance to oxidative stress and
CC starvation (PubMed:23593298). Together with thioredoxin reductase txtr-
CC 1, required for the reduction of disulfide groups in the cuticle during
CC molting (PubMed:21199936). {ECO:0000269|PubMed:21199936,
CC ECO:0000269|PubMed:23593298}.
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:23593298};
CC -!- COFACTOR:
CC Name=FAD; Xref=ChEBI:CHEBI:57692;
CC Evidence={ECO:0000250|UniProtKB:P00390};
CC Note=Binds 1 FAD per subunit. {ECO:0000250|UniProtKB:P00390};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=34.1 uM for glutathione disulfide (at 25 degrees Celsius)
CC {ECO:0000269|PubMed:23593298};
CC KM=12.9 uM for NADPH (at 25 degrees Celsius)
CC {ECO:0000269|PubMed:23593298};
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000305|PubMed:23593298}.
CC Mitochondrion {ECO:0000250|UniProtKB:P00390}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=a {ECO:0000312|WormBase:C46F11.2a};
CC IsoId=Q93379-1; Sequence=Displayed;
CC Name=b {ECO:0000312|WormBase:C46F11.2b};
CC IsoId=Q93379-2; Sequence=VSP_058343;
CC -!- TISSUE SPECIFICITY: Expressed at all larval stages and in adults in
CC intestine, vulva muscle, pharynx and some cells in the tail.
CC {ECO:0000269|PubMed:21199936, ECO:0000269|PubMed:23593298}.
CC -!- INDUCTION: Induced by the oxidant juglone and starvation.
CC {ECO:0000269|PubMed:23593298}.
CC -!- DISRUPTION PHENOTYPE: RNAi-mediated knockdown causes a severe decrease
CC in survival upon treatment with oxidants including juglone, paraquat
CC and to a lesser extent, cumen and tert-butylhydroperoxide (tBOOH).
CC Enhances further the production of gamma-glutamylycysteine and
CC glutathione disulfide upon juglone treatment. Increases gst-4 and gcs-1
CC expression. Reduces lifespan (PubMed:23593298). RNAi-mediated knockdown
CC in a trxr-1 mutant background causes an arrest during larval molting
CC characterized by a partial detachment of the old cuticle and an
CC impaired ability to reduce cuticle components (PubMed:21199936).
CC {ECO:0000269|PubMed:21199936, ECO:0000269|PubMed:23593298}.
CC -!- SIMILARITY: Belongs to the class-I pyridine nucleotide-disulfide
CC oxidoreductase family. {ECO:0000255|RuleBase:RU003691}.
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DR EMBL; BX284603; CAB03763.1; -; Genomic_DNA.
DR EMBL; BX284603; CAD88214.1; -; Genomic_DNA.
DR PIR; T19972; T19972.
DR RefSeq; NP_001021220.1; NM_001026049.5. [Q93379-1]
DR RefSeq; NP_001021221.1; NM_001026050.2.
DR AlphaFoldDB; Q93379; -.
DR SMR; Q93379; -.
DR DIP; DIP-27224N; -.
DR STRING; 6239.C46F11.2a; -.
DR World-2DPAGE; 0020:Q86DB5; -.
DR EPD; Q93379; -.
DR PaxDb; Q93379; -.
DR PeptideAtlas; Q93379; -.
DR EnsemblMetazoa; C46F11.2a.1; C46F11.2a.1; WBGene00008117. [Q93379-1]
DR EnsemblMetazoa; C46F11.2b.1; C46F11.2b.1; WBGene00008117. [Q93379-2]
DR EnsemblMetazoa; C46F11.2b.2; C46F11.2b.2; WBGene00008117. [Q93379-2]
DR GeneID; 175467; -.
DR KEGG; cel:CELE_C46F11.2; -.
DR UCSC; C46F11.2a; c. elegans.
DR CTD; 175467; -.
DR WormBase; C46F11.2a; CE17558; WBGene00008117; gsr-1. [Q93379-1]
DR WormBase; C46F11.2b; CE08773; WBGene00008117; gsr-1. [Q93379-2]
DR eggNOG; KOG0405; Eukaryota.
DR GeneTree; ENSGT00940000156986; -.
DR InParanoid; Q93379; -.
DR OMA; MSKHYDY; -.
DR OrthoDB; 581771at2759; -.
DR PhylomeDB; Q93379; -.
DR BRENDA; 1.8.1.7; 1045.
DR Reactome; R-CEL-3299685; Detoxification of Reactive Oxygen Species.
DR Reactome; R-CEL-499943; Interconversion of nucleotide di- and triphosphates.
DR Reactome; R-CEL-5628897; TP53 Regulates Metabolic Genes.
DR PRO; PR:Q93379; -.
DR Proteomes; UP000001940; Chromosome III.
DR Bgee; WBGene00008117; Expressed in germ line (C elegans) and 4 other tissues.
DR GO; GO:0005737; C:cytoplasm; IDA:WormBase.
DR GO; GO:0005829; C:cytosol; IDA:WormBase.
DR GO; GO:0005739; C:mitochondrion; IDA:WormBase.
DR GO; GO:0050660; F:flavin adenine dinucleotide binding; IBA:GO_Central.
DR GO; GO:0004362; F:glutathione-disulfide reductase (NADPH) activity; IDA:WormBase.
DR GO; GO:0050661; F:NADP binding; IEA:InterPro.
DR GO; GO:0045454; P:cell redox homeostasis; IMP:WormBase.
DR GO; GO:0034599; P:cellular response to oxidative stress; IBA:GO_Central.
DR GO; GO:0042395; P:ecdysis, collagen and cuticulin-based cuticle; IGI:WormBase.
DR GO; GO:0006749; P:glutathione metabolic process; IDA:WormBase.
DR GO; GO:0000303; P:response to superoxide; IMP:WormBase.
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 Alternative splicing; Cytoplasm; Disulfide bond; FAD; Flavoprotein;
KW Mitochondrion; NADP; Oxidoreductase; Redox-active center;
KW Reference proteome; Stress response; Transit peptide.
FT TRANSIT 1..?
FT /note="Mitochondrion"
FT /evidence="ECO:0000305|PubMed:23593298"
FT CHAIN ?..473
FT /note="Glutathione reductase, mitochondrial"
FT /evidence="ECO:0000305"
FT /id="PRO_0000436306"
FT ACT_SITE 456
FT /note="Proton acceptor"
FT /evidence="ECO:0000250|UniProtKB:P00390"
FT BINDING 50..58
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:P00390"
FT DISULFID 58..63
FT /note="Redox-active"
FT /evidence="ECO:0000250|UniProtKB:P00390"
FT VAR_SEQ 1..14
FT /note="Missing (in isoform b)"
FT /evidence="ECO:0000305"
FT /id="VSP_058343"
SQ SEQUENCE 473 AA; 51467 MW; E1DAA50758109D80 CRC64;
MLRFRCILST SRSIMSGVKE FDYLVIGGGS GGIASARRAR EFGVSVGLIE SGRLGGTCVN
VGCVPKKVMY NCSLHAEFIR DHADYGFDVT LNKFDWKVIK KSRDEYIKRL NGLYESGLKG
SSVEYIRGRA TFAEDGTVEV NGAKYRGKNT LIAVGGKPTI PNIKGAEHGI DSDGFFDLED
LPSRTVVVGA GYIAVEIAGV LANLGSDTHL LIRYDKVLRT FDKMLSDELT ADMDEETNPL
HLHKNTQVTE VIKGDDGLLT IKTTTGVIEK VQTLIWAIGR DPLTKELNLE RVGVKTDKSG
HIIVDEYQNT SAPGILSVGD DTGKFLLTPV AIAAGRRLSH RLFNGETDNK LTYENIATVV
FSHPLIGTVG LTEAEAVEKY GKDEVTLYKS RFNPMLFAVT KHKEKAAMKL VCVGKDEKVV
GVHVFGVGSD EMLQGFAVAV TMGATKKQFD QTVAIHPTSA EELVTMRGGV KPE
