GSH1_DROME
ID GSH1_DROME Reviewed; 717 AA.
AC Q9W3K5; Q9NGQ3;
DT 30-AUG-2002, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-2000, sequence version 1.
DT 03-AUG-2022, entry version 143.
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=Gclc; Synonyms=GCSh; ORFNames=CG2259;
OS Drosophila melanogaster (Fruit fly).
OC Eukaryota; Metazoa; Ecdysozoa; Arthropoda; Hexapoda; Insecta; Pterygota;
OC Neoptera; Endopterygota; Diptera; Brachycera; Muscomorpha; Ephydroidea;
OC Drosophilidae; Drosophila; Sophophora.
OX NCBI_TaxID=7227;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], AND FUNCTION.
RC TISSUE=Embryo;
RX PubMed=10675565; DOI=10.1016/s0014-5793(00)01148-0;
RA Saunders R.D.C., McLellan L.I.;
RT "Molecular cloning of Drosophila gamma-glutamylcysteine synthetase by
RT functional complementation of a yeast mutant.";
RL FEBS Lett. 467:337-340(2000).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RA Orr W.C., Sohal R.S.;
RT "Molecular organization of the gamma-glutamylcysteine synthetase gene in
RT Drosophila melanogaster.";
RL Submitted (MAR-2000) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Berkeley;
RX PubMed=10731132; DOI=10.1126/science.287.5461.2185;
RA Adams M.D., Celniker S.E., Holt R.A., Evans C.A., Gocayne J.D.,
RA Amanatides P.G., Scherer S.E., Li P.W., Hoskins R.A., Galle R.F.,
RA George R.A., Lewis S.E., Richards S., Ashburner M., Henderson S.N.,
RA Sutton G.G., Wortman J.R., Yandell M.D., Zhang Q., Chen L.X., Brandon R.C.,
RA Rogers Y.-H.C., Blazej R.G., Champe M., Pfeiffer B.D., Wan K.H., Doyle C.,
RA Baxter E.G., Helt G., Nelson C.R., Miklos G.L.G., Abril J.F., Agbayani A.,
RA An H.-J., Andrews-Pfannkoch C., Baldwin D., Ballew R.M., Basu A.,
RA Baxendale J., Bayraktaroglu L., Beasley E.M., Beeson K.Y., Benos P.V.,
RA Berman B.P., Bhandari D., Bolshakov S., Borkova D., Botchan M.R., Bouck J.,
RA Brokstein P., Brottier P., Burtis K.C., Busam D.A., Butler H., Cadieu E.,
RA Center A., Chandra I., Cherry J.M., Cawley S., Dahlke C., Davenport L.B.,
RA Davies P., de Pablos B., Delcher A., Deng Z., Mays A.D., Dew I.,
RA Dietz S.M., Dodson K., Doup L.E., Downes M., Dugan-Rocha S., Dunkov B.C.,
RA Dunn P., Durbin K.J., Evangelista C.C., Ferraz C., Ferriera S.,
RA Fleischmann W., Fosler C., Gabrielian A.E., Garg N.S., Gelbart W.M.,
RA Glasser K., Glodek A., Gong F., Gorrell J.H., Gu Z., Guan P., Harris M.,
RA Harris N.L., Harvey D.A., Heiman T.J., Hernandez J.R., Houck J., Hostin D.,
RA Houston K.A., Howland T.J., Wei M.-H., Ibegwam C., Jalali M., Kalush F.,
RA Karpen G.H., Ke Z., Kennison J.A., Ketchum K.A., Kimmel B.E., Kodira C.D.,
RA Kraft C.L., Kravitz S., Kulp D., Lai Z., Lasko P., Lei Y., Levitsky A.A.,
RA Li J.H., Li Z., Liang Y., Lin X., Liu X., Mattei B., McIntosh T.C.,
RA McLeod M.P., McPherson D., Merkulov G., Milshina N.V., Mobarry C.,
RA Morris J., Moshrefi A., Mount S.M., Moy M., Murphy B., Murphy L.,
RA Muzny D.M., Nelson D.L., Nelson D.R., Nelson K.A., Nixon K., Nusskern D.R.,
RA Pacleb J.M., Palazzolo M., Pittman G.S., Pan S., Pollard J., Puri V.,
RA Reese M.G., Reinert K., Remington K., Saunders R.D.C., Scheeler F.,
RA Shen H., Shue B.C., Siden-Kiamos I., Simpson M., Skupski M.P., Smith T.J.,
RA Spier E., Spradling A.C., Stapleton M., Strong R., Sun E., Svirskas R.,
RA Tector C., Turner R., Venter E., Wang A.H., Wang X., Wang Z.-Y.,
RA Wassarman D.A., Weinstock G.M., Weissenbach J., Williams S.M., Woodage T.,
RA Worley K.C., Wu D., Yang S., Yao Q.A., Ye J., Yeh R.-F., Zaveri J.S.,
RA Zhan M., Zhang G., Zhao Q., Zheng L., Zheng X.H., Zhong F.N., Zhong W.,
RA Zhou X., Zhu S.C., Zhu X., Smith H.O., Gibbs R.A., Myers E.W., Rubin G.M.,
RA Venter J.C.;
RT "The genome sequence of Drosophila melanogaster.";
RL Science 287:2185-2195(2000).
RN [4]
RP GENOME REANNOTATION.
RC STRAIN=Berkeley;
RX PubMed=12537572; DOI=10.1186/gb-2002-3-12-research0083;
RA Misra S., Crosby M.A., Mungall C.J., Matthews B.B., Campbell K.S.,
RA Hradecky P., Huang Y., Kaminker J.S., Millburn G.H., Prochnik S.E.,
RA Smith C.D., Tupy J.L., Whitfield E.J., Bayraktaroglu L., Berman B.P.,
RA Bettencourt B.R., Celniker S.E., de Grey A.D.N.J., Drysdale R.A.,
RA Harris N.L., Richter J., Russo S., Schroeder A.J., Shu S.Q., Stapleton M.,
RA Yamada C., Ashburner M., Gelbart W.M., Rubin G.M., Lewis S.E.;
RT "Annotation of the Drosophila melanogaster euchromatic genome: a systematic
RT review.";
RL Genome Biol. 3:RESEARCH0083.1-RESEARCH0083.22(2002).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=Berkeley; TISSUE=Embryo;
RX PubMed=12537569; DOI=10.1186/gb-2002-3-12-research0080;
RA Stapleton M., Carlson J.W., Brokstein P., Yu C., Champe M., George R.A.,
RA Guarin H., Kronmiller B., Pacleb J.M., Park S., Wan K.H., Rubin G.M.,
RA Celniker S.E.;
RT "A Drosophila full-length cDNA resource.";
RL Genome Biol. 3:RESEARCH0080.1-RESEARCH0080.8(2002).
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 -!- SIMILARITY: Belongs to the glutamate--cysteine ligase type 3 family.
CC {ECO:0000305}.
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DR EMBL; AF244351; AAF66980.1; -; mRNA.
DR EMBL; AE014298; AAF46321.1; -; Genomic_DNA.
DR EMBL; AY071586; AAL49208.1; -; mRNA.
DR RefSeq; NP_001285001.1; NM_001298072.1.
DR RefSeq; NP_001285002.1; NM_001298073.1.
DR RefSeq; NP_525005.2; NM_080266.3.
DR RefSeq; NP_996373.1; NM_206650.2.
DR AlphaFoldDB; Q9W3K5; -.
DR SMR; Q9W3K5; -.
DR BioGRID; 72805; 3.
DR IntAct; Q9W3K5; 2.
DR STRING; 7227.FBpp0071063; -.
DR PaxDb; Q9W3K5; -.
DR PRIDE; Q9W3K5; -.
DR EnsemblMetazoa; FBtr0071107; FBpp0071063; FBgn0040319.
DR EnsemblMetazoa; FBtr0071108; FBpp0089361; FBgn0040319.
DR EnsemblMetazoa; FBtr0340138; FBpp0309124; FBgn0040319.
DR EnsemblMetazoa; FBtr0340139; FBpp0309125; FBgn0040319.
DR GeneID; 53581; -.
DR KEGG; dme:Dmel_CG2259; -.
DR CTD; 2729; -.
DR FlyBase; FBgn0040319; Gclc.
DR VEuPathDB; VectorBase:FBgn0040319; -.
DR eggNOG; KOG3754; Eukaryota.
DR GeneTree; ENSGT00390000011908; -.
DR HOGENOM; CLU_010467_0_0_1; -.
DR InParanoid; Q9W3K5; -.
DR OMA; YISQDPR; -.
DR OrthoDB; 575052at2759; -.
DR PhylomeDB; Q9W3K5; -.
DR BRENDA; 6.3.2.2; 1994.
DR Reactome; R-DME-174403; Glutathione synthesis and recycling.
DR UniPathway; UPA00142; UER00209.
DR BioGRID-ORCS; 53581; 2 hits in 3 CRISPR screens.
DR GenomeRNAi; 53581; -.
DR PRO; PR:Q9W3K5; -.
DR Proteomes; UP000000803; Chromosome X.
DR Bgee; FBgn0040319; Expressed in adult Malpighian tubule (Drosophila) and 15 other tissues.
DR ExpressionAtlas; Q9W3K5; baseline and differential.
DR Genevisible; Q9W3K5; DM.
DR GO; GO:0017109; C:glutamate-cysteine ligase complex; IPI:FlyBase.
DR GO; GO:0005634; C:nucleus; IDA:FlyBase.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; IDA:FlyBase.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0004357; F:glutamate-cysteine ligase activity; IDA:FlyBase.
DR GO; GO:0007409; P:axonogenesis; IMP:FlyBase.
DR GO; GO:0006750; P:glutathione biosynthetic process; IDA:FlyBase.
DR GO; GO:0006749; P:glutathione metabolic process; IDA:FlyBase.
DR GO; GO:0007476; P:imaginal disc-derived wing morphogenesis; IMP:FlyBase.
DR GO; GO:0046688; P:response to copper ion; IDA:FlyBase.
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 2: Evidence at transcript level;
KW ATP-binding; Glutathione biosynthesis; Ligase; Nucleotide-binding;
KW Reference proteome.
FT CHAIN 1..717
FT /note="Glutamate--cysteine ligase"
FT /id="PRO_0000192568"
FT REGION 484..576
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 489..568
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT CONFLICT 35
FT /note="H -> Y (in Ref. 2; AAF66980)"
FT /evidence="ECO:0000305"
FT CONFLICT 53..64
FT /note="YIIVKFDDEQKV -> SLLSSSTMTAA (in Ref. 2; AAF66980)"
FT /evidence="ECO:0000305"
FT CONFLICT 502
FT /note="A -> AQA (in Ref. 2)"
FT /evidence="ECO:0000305"
FT CONFLICT 530
FT /note="S -> G (in Ref. 2; AAF66980)"
FT /evidence="ECO:0000305"
FT CONFLICT 550
FT /note="S -> N (in Ref. 2; AAF66980)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 717 AA; 80746 MW; E0C555163E370488 CRC64;
MGLLSEGSPL SWEETKALAD HVREHGVNQF INLYHRLKDR QGDILKWGDE VEYIIVKFDD
EQKVARVALR AQDLLAQLNE KELADPNGVK SLWRPEYGAY MIEGTPGKPF GGLMAHFNLV
EANMRYRREE VTELLAKDEC VMSITNFPRL GAPNFTYPLA QPRPEDPLSS ARSLYFPDEA
IFPGHPRFKT LTRNIRKRRG EKVSIKLKVF KDTKTKLPVE GAPPGEPDVV LLDAMGFGMG
CCCLQLTFQA CNITEARRLY DQLAPLCPIM LALTAASPIY RGYLTESDCR WNVISSSVDC
RTEEERGLAP LDQQKFRIAK SRYDSIDSYL SPEGAKYNDV PLTYDEKVYQ RLVEGGIDHL
LAQHVAHLFI RDTVSLFSEK VHQNDNEDTD HFENIQSTNW QTMRFKPPPP NSSIGWRVEF
RPCEAQISDF ENAAIVCFVV LLTRVILSYQ LNFLTPISKV DENMQTAQKR DACRKEKFWF
RKSSKTTEQR AAKAQAQAQA QAKAQAQTNG KATLNGNGLA NGNGNGSENS DQEEQQPLTN
GSAKMNGHGS GTTNGTNGSS NGSSNGTDSD HTDTDDEENE LFQLLSINEI FNGKPNVFPG
LVPLIRSYLQ SMEVDTDTHC TIEQYLRFIQ KRAAGELITT ATWMREQVLS HPDYKQDSVV
SERINYDLLK RIQGIQEGKQ VEPALLGQDY HSKTKTKDFI PPALQKQLAK NGCCEEK
