GSH1_CAEEL
ID GSH1_CAEEL Reviewed; 654 AA.
AC Q20117;
DT 30-AUG-2002, integrated into UniProtKB/Swiss-Prot.
DT 11-APR-2003, sequence version 2.
DT 03-AUG-2022, entry version 141.
DE RecName: Full=Glutamate--cysteine ligase;
DE EC=6.3.2.2;
DE AltName: Full=Gamma-ECS;
DE Short=GCS;
DE AltName: Full=Gamma-glutamylcysteine synthetase;
GN Name=gcs-1; ORFNames=F37B12.2;
OS Caenorhabditis elegans.
OC Eukaryota; Metazoa; Ecdysozoa; Nematoda; Chromadorea; Rhabditida;
OC Rhabditina; Rhabditomorpha; Rhabditoidea; Rhabditidae; Peloderinae;
OC Caenorhabditis.
OX NCBI_TaxID=6239;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Bristol N2;
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]
RP TISSUE SPECIFICITY, AND INDUCTION BY ARSENITE.
RX PubMed=16166371; DOI=10.1101/gad.1324805;
RA Inoue H., Hisamoto N., An J.H., Oliveira R.P., Nishida E., Blackwell T.K.,
RA Matsumoto K.;
RT "The C. elegans p38 MAPK pathway regulates nuclear localization of the
RT transcription factor SKN-1 in oxidative stress response.";
RL Genes Dev. 19:2278-2283(2005).
RN [3]
RP FUNCTION.
RX PubMed=22216003; DOI=10.1371/journal.ppat.1002453;
RA Hoeven R.V., McCallum K.C., Cruz M.R., Garsin D.A.;
RT "Ce-Duox1/BLI-3 generated reactive oxygen species trigger protective SKN-1
RT activity via p38 MAPK signaling during infection in C. elegans.";
RL PLoS Pathog. 7:E1002453-E1002453(2011).
RN [4]
RP FUNCTION, 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 [5]
RP FUNCTION, 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: Plays a role in resistance to arsenite (PubMed:23593298). May
CC play a role in the oxidative stress response induced by reactive oxygen
CC species produced during infection by pathogenic bacteria
CC (PubMed:22216003). Together with trxr-1, required for the reduction of
CC disulfide groups in the cuticle during molting (PubMed:21199936).
CC {ECO:0000269|PubMed:21199936, ECO:0000269|PubMed:22216003,
CC ECO:0000269|PubMed:23593298}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-cysteine + L-glutamate = ADP + gamma-L-glutamyl-L-
CC cysteine + H(+) + phosphate; Xref=Rhea:RHEA:13285, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:29985, ChEBI:CHEBI:30616, ChEBI:CHEBI:35235,
CC ChEBI:CHEBI:43474, ChEBI:CHEBI:58173, ChEBI:CHEBI:456216; EC=6.3.2.2;
CC -!- PATHWAY: Sulfur metabolism; glutathione biosynthesis; glutathione from
CC L-cysteine and L-glutamate: step 1/2.
CC -!- INTERACTION:
CC Q20117; Q966L2: E01A2.1; NbExp=2; IntAct=EBI-311822, EBI-311817;
CC -!- TISSUE SPECIFICITY: Expressed in intestine upon arsenite treatment.
CC {ECO:0000269|PubMed:16166371}.
CC -!- INDUCTION: By oxidative stress such as arsenite treatment.
CC {ECO:0000269|PubMed:16166371}.
CC -!- DISRUPTION PHENOTYPE: RNAi-mediated knockdown of gsr-1 in mutants
CC lacking trxr-1 causes an arrest during larval molting characterized by
CC a partial detachment of the old cuticle and an impaired ability to
CC reduce cuticle components. Also results in growth arrest during the
CC postdauer molt (PubMed:21199936). RNAi-mediated knockdown causes a
CC severe loss of viability upon arsenite treatment (PubMed:23593298).
CC {ECO:0000269|PubMed:21199936, ECO:0000269|PubMed:23593298}.
CC -!- SIMILARITY: Belongs to the glutamate--cysteine ligase type 3 family.
CC {ECO:0000305}.
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DR EMBL; Z54218; CAA90955.2; -; Genomic_DNA.
DR PIR; T21908; T21908.
DR RefSeq; NP_495927.2; NM_063526.5.
DR AlphaFoldDB; Q20117; -.
DR SMR; Q20117; -.
DR BioGRID; 39765; 9.
DR IntAct; Q20117; 1.
DR STRING; 6239.F37B12.2; -.
DR EPD; Q20117; -.
DR PaxDb; Q20117; -.
DR PeptideAtlas; Q20117; -.
DR EnsemblMetazoa; F37B12.2.1; F37B12.2.1; WBGene00001527.
DR GeneID; 174438; -.
DR KEGG; cel:CELE_F37B12.2; -.
DR UCSC; F37B12.2.1; c. elegans.
DR CTD; 174438; -.
DR WormBase; F37B12.2; CE32886; WBGene00001527; gcs-1.
DR eggNOG; KOG3754; Eukaryota.
DR GeneTree; ENSGT00390000011908; -.
DR HOGENOM; CLU_010467_0_0_1; -.
DR InParanoid; Q20117; -.
DR OMA; YISQDPR; -.
DR OrthoDB; 575052at2759; -.
DR PhylomeDB; Q20117; -.
DR Reactome; R-CEL-174403; Glutathione synthesis and recycling.
DR UniPathway; UPA00142; UER00209.
DR PRO; PR:Q20117; -.
DR Proteomes; UP000001940; Chromosome II.
DR Bgee; WBGene00001527; Expressed in pharyngeal muscle cell (C elegans) and 4 other tissues.
DR GO; GO:0017109; C:glutamate-cysteine ligase complex; IBA:GO_Central.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0004357; F:glutamate-cysteine ligase activity; IBA:GO_Central.
DR GO; GO:0006750; P:glutathione biosynthetic process; IMP:WormBase.
DR GO; GO:0046685; P:response to arsenic-containing substance; IMP:WormBase.
DR GO; GO:0009408; P:response to heat; IEP:WormBase.
DR GO; GO:0000302; P:response to reactive oxygen species; IMP:WormBase.
DR GO; GO:0000303; P:response to superoxide; IEP:WormBase.
DR InterPro; IPR004308; GCS.
DR InterPro; IPR014746; Gln_synth/guanido_kin_cat_dom.
DR PANTHER; PTHR11164; PTHR11164; 1.
DR Pfam; PF03074; GCS; 1.
DR SUPFAM; SSF55931; SSF55931; 1.
PE 1: Evidence at protein level;
KW ATP-binding; Glutathione biosynthesis; Ligase; Nucleotide-binding;
KW Reference proteome; Stress response.
FT CHAIN 1..654
FT /note="Glutamate--cysteine ligase"
FT /id="PRO_0000192566"
SQ SEQUENCE 654 AA; 74369 MW; 37EA2F5DFC2BEAB5 CRC64;
MGLLTKGSPL TWAETVPHID YIKKHGIAQF INLYHRLKSR HGDQLKWGDE IEYTIVKFDD
ANKKVRVSCK AEELLNKLQA EEQVNAMLGT ANRFLWRPEF GSYMIEGTPG MPYGGLIACF
NIVEANMKLR RQVVKKLLKK DETCLSISFP SLGVPGFTFP EVAADRKNDD AANSVFWPEQ
AVFLGHPRFK NLTKNIKGRR GSKVAINVPI FKDTNTPSPF VEDLSALGGP DDTRDAKPDH
IYMDHMGFGM GCCCLQVTFQ AVNVDEARWL YDQLTPITPI LLALSAATPI FRGKLSNVDS
RWDIISASVD DRTPEERGLE PLKNSKWVID KSRYDSTDCY IYPCSVGYND IPLQYDETIY
KQLIDGNIDE PLAKHIAHMF IRDPHQVFRE RIEQDDEKSS EHFETIQSSN WMNMRFKPPP
PDAPEIGWRV EFRPTEVQLT DFENAAYCCF VVLLTRMMIS FRLTYLMPIS MVTENMKRAQ
QKDAVLNQKF LFRKGLAECK SAPENLKGSE KCGPPSQDIE EMSIDEIING KKNGFPGLIS
LIRQFLDSAD VDVDTRCTIS QYLNFISKRA TGEINTLAHW TRGFVQSHPA YKHDSDVNDN
IVYDLLKKMD AISNGEDHCE KLLGCYRSKT DHAISAAVRK AEEHMIVSSQ KRAH
