GSH1_MOUSE
ID GSH1_MOUSE Reviewed; 637 AA.
AC P97494; O09166; Q8VCS5;
DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 4.
DT 03-AUG-2022, entry version 166.
DE RecName: Full=Glutamate--cysteine ligase catalytic subunit;
DE EC=6.3.2.2;
DE AltName: Full=GCS heavy chain;
DE AltName: Full=Gamma-ECS;
DE AltName: Full=Gamma-glutamylcysteine synthetase;
GN Name=Gclc; Synonyms=Glclc;
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].
RC TISSUE=Liver;
RX PubMed=9223101; DOI=10.1097/00001756-199705260-00049;
RA Kang Y., Oiao X., Jurma O., Knusel B., Andersen J.K.;
RT "Cloning/brain localization of mouse glutamylcysteine synthetase heavy
RT chain mRNA.";
RL NeuroReport 8:2053-2060(1997).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=C57BL/6J; TISSUE=Kidney;
RX PubMed=9224945; DOI=10.1016/s0167-4781(97)00058-4;
RA Reid L.L., Botta D., Lu Y., Gallagher E.P., Kavanagh T.J.;
RT "Molecular cloning and sequencing of the cDNA encoding the catalytic
RT subunit of mouse glutamate-cysteine ligase.";
RL Biochim. Biophys. Acta 1352:233-237(1997).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Liver;
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 [4]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Brown adipose tissue, Kidney, Liver, Lung, Pancreas, Spleen,
RC 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).
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 -!- ACTIVITY REGULATION: Feedback inhibition by glutathione.
CC -!- PATHWAY: Sulfur metabolism; glutathione biosynthesis; glutathione from
CC L-cysteine and L-glutamate: step 1/2.
CC -!- SUBUNIT: Heterodimer of a catalytic heavy chain and a regulatory light
CC chain.
CC -!- SIMILARITY: Belongs to the glutamate--cysteine ligase type 3 family.
CC {ECO:0000305}.
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DR EMBL; U85414; AAB42020.1; -; mRNA.
DR EMBL; U85498; AAB52542.1; -; mRNA.
DR EMBL; BC019374; AAH19374.1; -; mRNA.
DR CCDS; CCDS23354.1; -.
DR RefSeq; NP_034425.1; NM_010295.2.
DR AlphaFoldDB; P97494; -.
DR SMR; P97494; -.
DR BioGRID; 199940; 3.
DR STRING; 10090.ENSMUSP00000034905; -.
DR ChEMBL; CHEMBL2366483; -.
DR iPTMnet; P97494; -.
DR PhosphoSitePlus; P97494; -.
DR SwissPalm; P97494; -.
DR CPTAC; non-CPTAC-3976; -.
DR EPD; P97494; -.
DR jPOST; P97494; -.
DR PaxDb; P97494; -.
DR PeptideAtlas; P97494; -.
DR PRIDE; P97494; -.
DR ProteomicsDB; 269639; -.
DR Antibodypedia; 4035; 430 antibodies from 35 providers.
DR DNASU; 14629; -.
DR Ensembl; ENSMUST00000034905; ENSMUSP00000034905; ENSMUSG00000032350.
DR GeneID; 14629; -.
DR KEGG; mmu:14629; -.
DR UCSC; uc009qtm.2; mouse.
DR CTD; 2729; -.
DR MGI; MGI:104990; Gclc.
DR VEuPathDB; HostDB:ENSMUSG00000032350; -.
DR eggNOG; KOG3754; Eukaryota.
DR GeneTree; ENSGT00390000011908; -.
DR HOGENOM; CLU_010467_0_0_1; -.
DR InParanoid; P97494; -.
DR OMA; YISQDPR; -.
DR OrthoDB; 575052at2759; -.
DR PhylomeDB; P97494; -.
DR TreeFam; TF105644; -.
DR BRENDA; 6.3.2.2; 3474.
DR Reactome; R-MMU-174403; Glutathione synthesis and recycling.
DR SABIO-RK; P97494; -.
DR UniPathway; UPA00142; UER00209.
DR BioGRID-ORCS; 14629; 20 hits in 74 CRISPR screens.
DR ChiTaRS; Gclc; mouse.
DR PRO; PR:P97494; -.
DR Proteomes; UP000000589; Chromosome 9.
DR RNAct; P97494; protein.
DR Bgee; ENSMUSG00000032350; Expressed in epithelium of stomach and 275 other tissues.
DR ExpressionAtlas; P97494; baseline and differential.
DR Genevisible; P97494; MM.
DR GO; GO:0005829; C:cytosol; IDA:MGI.
DR GO; GO:0017109; C:glutamate-cysteine ligase complex; IDA:MGI.
DR GO; GO:0005739; C:mitochondrion; IEA:GOC.
DR GO; GO:0043531; F:ADP binding; ISS:UniProtKB.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0016595; F:glutamate binding; ISS:UniProtKB.
DR GO; GO:0004357; F:glutamate-cysteine ligase activity; IDA:MGI.
DR GO; GO:0000287; F:magnesium ion binding; ISS:UniProtKB.
DR GO; GO:0044877; F:protein-containing complex binding; ISO:MGI.
DR GO; GO:0007568; P:aging; IEA:Ensembl.
DR GO; GO:0097746; P:blood vessel diameter maintenance; ISS:UniProtKB.
DR GO; GO:0045454; P:cell redox homeostasis; ISS:UniProtKB.
DR GO; GO:0044344; P:cellular response to fibroblast growth factor stimulus; IEA:Ensembl.
DR GO; GO:0071372; P:cellular response to follicle-stimulating hormone stimulus; IEA:Ensembl.
DR GO; GO:0071333; P:cellular response to glucose stimulus; IEA:Ensembl.
DR GO; GO:0035729; P:cellular response to hepatocyte growth factor stimulus; IEA:Ensembl.
DR GO; GO:0032869; P:cellular response to insulin stimulus; IEA:Ensembl.
DR GO; GO:0071260; P:cellular response to mechanical stimulus; IEA:Ensembl.
DR GO; GO:0097069; P:cellular response to thyroxine stimulus; IEA:Ensembl.
DR GO; GO:0006534; P:cysteine metabolic process; ISS:UniProtKB.
DR GO; GO:0006536; P:glutamate metabolic process; ISS:UniProtKB.
DR GO; GO:0006750; P:glutathione biosynthetic process; IDA:MGI.
DR GO; GO:0006749; P:glutathione metabolic process; IMP:MGI.
DR GO; GO:0019852; P:L-ascorbic acid metabolic process; IMP:MGI.
DR GO; GO:0043066; P:negative regulation of apoptotic process; ISS:UniProtKB.
DR GO; GO:2001237; P:negative regulation of extrinsic apoptotic signaling pathway; IGI:MGI.
DR GO; GO:2000490; P:negative regulation of hepatic stellate cell activation; ISO:MGI.
DR GO; GO:1901029; P:negative regulation of mitochondrial outer membrane permeabilization involved in apoptotic signaling pathway; IGI:MGI.
DR GO; GO:0043524; P:negative regulation of neuron apoptotic process; ISO:MGI.
DR GO; GO:0031397; P:negative regulation of protein ubiquitination; IMP:MGI.
DR GO; GO:0045892; P:negative regulation of transcription, DNA-templated; ISS:UniProtKB.
DR GO; GO:0032436; P:positive regulation of proteasomal ubiquitin-dependent protein catabolic process; IMP:MGI.
DR GO; GO:0051900; P:regulation of mitochondrial depolarization; IGI:MGI.
DR GO; GO:0014823; P:response to activity; IEA:Ensembl.
DR GO; GO:0046685; P:response to arsenic-containing substance; IMP:MGI.
DR GO; GO:0046686; P:response to cadmium ion; IEA:Ensembl.
DR GO; GO:0009408; P:response to heat; ISS:UniProtKB.
DR GO; GO:0009725; P:response to hormone; ISS:UniProtKB.
DR GO; GO:0044752; P:response to human chorionic gonadotropin; IEA:Ensembl.
DR GO; GO:0070555; P:response to interleukin-1; IEA:Ensembl.
DR GO; GO:0051409; P:response to nitrosative stress; ISO:MGI.
DR GO; GO:0007584; P:response to nutrient; IEA:Ensembl.
DR GO; GO:0006979; P:response to oxidative stress; ISS:UniProtKB.
DR GO; GO:0009410; P:response to xenobiotic stimulus; IMP:MGI.
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 Acetylation; ATP-binding; Glutathione biosynthesis; Ligase;
KW Nucleotide-binding; Phosphoprotein; Reference proteome.
FT CHAIN 1..637
FT /note="Glutamate--cysteine ligase catalytic subunit"
FT /id="PRO_0000192564"
FT MOD_RES 1
FT /note="N-acetylmethionine"
FT /evidence="ECO:0000250|UniProtKB:P48506"
FT MOD_RES 5
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P48506"
FT MOD_RES 8
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P48506"
FT CONFLICT 6
FT /note="Q -> H (in Ref. 1; AAB42020)"
FT /evidence="ECO:0000305"
FT CONFLICT 25..26
FT /note="HG -> RD (in Ref. 1; AAB42020)"
FT /evidence="ECO:0000305"
FT CONFLICT 32
FT /note="H -> Q (in Ref. 3; AAH19374)"
FT /evidence="ECO:0000305"
FT CONFLICT 500
FT /note="G -> E (in Ref. 1; AAB42020)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 637 AA; 72571 MW; 8A176CD1DE49094C CRC64;
MGLLSQGSPL SWEETQRHAD HVRRHGILQF LHIYHAVKDR HKDVLKWGDE VEYMLVSFDH
ENRKVQLLLN GGDVLETLQE KGERTNPNHP TLWRPEYGSY MIEGTPGQPY GGTMSEFNTV
EANMRKRRKE ATSVLGEHQA LCTITSFPRL GCPGFTLPEH RPNPEEGGAS KSLFFPDEAI
NKHPRFGTLT RNIRHRRGEK VVINVPIFKD KNTPSPFVET FPEDAEASKA SQPDHIYMDA
MGFGMGNCCL QVTFQACSIS EARYLYDQLA TICPIVMALS AASPFYRGYV SDIDCRWGVI
SASVDDRTRE ERGLEPLKNN RFRISKSRYD SIDSYLSKCG EKYNDIDLTI DKEIYEQLLE
EGIDHLLAQH VAHLFIRDPL TLFEEKIHLD DANESDHFEN IQSTNWQTMR FKPPPPNSDI
GWRVEFRPME VQLTDFENSA YVVFVVLLTR VILSYKLDFL IPLSKVDENM KVAQKRDAVL
QGMFYFRKDI CKGGNAVVDG CSKAQSSSEP AAEEYTLMSI DTIINGKEGV FPGLIPILNS
YLENMEVDVD TRCSILNYLK LIKKRASGEL MTVARWMREF IANHPDYKQD SVITDEINYS
LIWKCNQIAD ELCECPELLG SGFRKAKYSG GKSDPSA
