ID GSHB_MOUSE Reviewed; 474 AA. AC P51855; DT 01-OCT-1996, integrated into UniProtKB/Swiss-Prot. DT 01-OCT-1996, sequence version 1. DT 24-JAN-2024, entry version 176. DE RecName: Full=Glutathione synthetase {ECO:0000303|PubMed:8660701}; DE Short=GSH synthetase; DE Short=GSH-S; DE EC=6.3.2.3 {ECO:0000250|UniProtKB:P48637}; DE AltName: Full=Glutathione synthase; GN Name=Gss {ECO:0000312|MGI:MGI:95852}; 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 STRAIN=C57BL/6J; TISSUE=Kidney; RX PubMed=8660701; DOI=10.1006/abbi.1996.0301; RA Shi Z.Z., Carter B.Z., Habib G.M., He X., Sazer S., Lebovitz R.M., RA Lieberman M.W.; RT "A single mouse glutathione synthetase gene encodes six mRNAs with RT different 5' ends."; RL Arch. Biochem. Biophys. 331:215-224(1996). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. 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 [3] RP FUNCTION, AND CATALYTIC ACTIVITY. RX PubMed=16608839; DOI=10.1074/jbc.m601876200; RA Soga T., Baran R., Suematsu M., Ueno Y., Ikeda S., Sakurakawa T., RA Kakazu Y., Ishikawa T., Robert M., Nishioka T., Tomita M.; RT "Differential metabolomics reveals ophthalmic acid as an oxidative stress RT biomarker indicating hepatic glutathione consumption."; RL J. Biol. Chem. 281:16768-16776(2006). RN [4] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Brain, Brown adipose tissue, Heart, Kidney, Liver, Lung, 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). CC -!- FUNCTION: Catalyzes the production of glutathione from gamma- CC glutamylcysteine and glycine in an ATP-dependent manner. Glutathione CC (gamma-glutamylcysteinylglycine, GSH) is the most abundant CC intracellular thiol in living aerobic cells and is required for CC numerous processes including the protection of cells against oxidative CC damage, amino acid transport, the detoxification of foreign compounds, CC the maintenance of protein sulfhydryl groups in a reduced state and CC acts as a cofactor for a number of enzymes. Participates in ophthalmate CC biosynthesis in hepatocytes (PubMed:16608839). CC {ECO:0000250|UniProtKB:P48637, ECO:0000269|PubMed:16608839}. CC -!- CATALYTIC ACTIVITY: CC Reaction=ATP + gamma-L-glutamyl-L-cysteine + glycine = ADP + CC glutathione + H(+) + phosphate; Xref=Rhea:RHEA:13557, CC ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:43474, CC ChEBI:CHEBI:57305, ChEBI:CHEBI:57925, ChEBI:CHEBI:58173, CC ChEBI:CHEBI:456216; EC=6.3.2.3; CC Evidence={ECO:0000250|UniProtKB:P48637}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:13558; CC Evidence={ECO:0000250|UniProtKB:P48637}; CC -!- CATALYTIC ACTIVITY: CC Reaction=ATP + gamma-L-glutamyl-(2S)-2-aminobutanoate + glycine = ADP + CC H(+) + ophthalmate + phosphate; Xref=Rhea:RHEA:72075, CC ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:43474, CC ChEBI:CHEBI:57305, ChEBI:CHEBI:189406, ChEBI:CHEBI:189750, CC ChEBI:CHEBI:456216; Evidence={ECO:0000269|PubMed:16608839}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:72076; CC Evidence={ECO:0000269|PubMed:16608839}; CC -!- COFACTOR: CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420; CC Evidence={ECO:0000250|UniProtKB:P48637}; CC Note=Binds 1 Mg(2+) ion per subunit. {ECO:0000250|UniProtKB:P48637}; CC -!- PATHWAY: Sulfur metabolism; glutathione biosynthesis; glutathione from CC L-cysteine and L-glutamate: step 2/2. {ECO:0000250|UniProtKB:P48637}. CC -!- SUBUNIT: Homodimer. {ECO:0000250|UniProtKB:P48637}. CC -!- SIMILARITY: Belongs to the eukaryotic GSH synthase family. CC {ECO:0000305}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; U35456; AAB09730.1; -; mRNA. DR EMBL; BC003784; AAH03784.1; -; mRNA. DR CCDS; CCDS16951.1; -. DR PIR; S71322; S71322. DR RefSeq; NP_032206.1; NM_008180.2. DR RefSeq; XP_006498844.1; XM_006498781.2. DR AlphaFoldDB; P51855; -. DR SMR; P51855; -. DR BioGRID; 200089; 8. DR STRING; 10090.ENSMUSP00000078630; -. DR iPTMnet; P51855; -. DR PhosphoSitePlus; P51855; -. DR SwissPalm; P51855; -. DR EPD; P51855; -. DR jPOST; P51855; -. DR PaxDb; 10090-ENSMUSP00000078630; -. DR PeptideAtlas; P51855; -. DR ProteomicsDB; 271446; -. DR Pumba; P51855; -. DR Antibodypedia; 25920; 502 antibodies from 34 providers. DR DNASU; 14854; -. DR Ensembl; ENSMUST00000079691.13; ENSMUSP00000078630.7; ENSMUSG00000027610.18. DR GeneID; 14854; -. DR KEGG; mmu:14854; -. DR UCSC; uc008nkx.2; mouse. DR AGR; MGI:95852; -. DR CTD; 2937; -. DR MGI; MGI:95852; Gss. DR VEuPathDB; HostDB:ENSMUSG00000027610; -. DR eggNOG; KOG0021; Eukaryota. DR GeneTree; ENSGT00390000013764; -. DR InParanoid; P51855; -. DR OMA; NGLVMYP; -. DR OrthoDB; 1448at2759; -. DR PhylomeDB; P51855; -. DR TreeFam; TF105187; -. DR Reactome; R-MMU-174403; Glutathione synthesis and recycling. DR SABIO-RK; P51855; -. DR UniPathway; UPA00142; UER00210. DR BioGRID-ORCS; 14854; 12 hits in 81 CRISPR screens. DR ChiTaRS; Gss; mouse. DR PRO; PR:P51855; -. DR Proteomes; UP000000589; Chromosome 2. DR RNAct; P51855; Protein. DR Bgee; ENSMUSG00000027610; Expressed in right kidney and 208 other cell types or tissues. DR ExpressionAtlas; P51855; baseline and differential. DR GO; GO:0005829; C:cytosol; IBA:GO_Central. DR GO; GO:0005524; F:ATP binding; ISS:UniProtKB. DR GO; GO:0043295; F:glutathione binding; ISS:UniProtKB. DR GO; GO:0004363; F:glutathione synthase activity; IDA:MGI. DR GO; GO:0016594; F:glycine binding; ISO:MGI. DR GO; GO:0042802; F:identical protein binding; ISO:MGI. DR GO; GO:0000287; F:magnesium ion binding; ISS:UniProtKB. DR GO; GO:0042277; F:peptide binding; ISO:MGI. DR GO; GO:0042803; F:protein homodimerization activity; ISS:UniProtKB. DR GO; GO:0006750; P:glutathione biosynthetic process; ISO:MGI. DR GO; GO:0046686; P:response to cadmium ion; IDA:MGI. DR CDD; cd00228; eu-GS; 1. DR Gene3D; 3.30.1490.50; -; 1. DR Gene3D; 3.30.1490.80; -; 1. DR Gene3D; 3.30.470.20; ATP-grasp fold, B domain; 1. DR Gene3D; 3.40.50.1760; Glutathione synthase, substrate-binding domain superfamily, eukaryotic; 1. DR InterPro; IPR005615; Glutathione_synthase. DR InterPro; IPR014042; Glutathione_synthase_a-hlx. DR InterPro; IPR014709; Glutathione_synthase_C_euk. DR InterPro; IPR014049; Glutathione_synthase_N_euk. DR InterPro; IPR037013; GSH-S_sub-bd_sf. DR InterPro; IPR004887; GSH_synth_subst-bd. DR InterPro; IPR016185; PreATP-grasp_dom_sf. DR NCBIfam; TIGR01986; glut_syn_euk; 1. DR PANTHER; PTHR11130; GLUTATHIONE SYNTHETASE; 1. DR PANTHER; PTHR11130:SF0; GLUTATHIONE SYNTHETASE; 1. DR Pfam; PF03917; GSH_synth_ATP; 1. DR Pfam; PF03199; GSH_synthase; 1. DR PIRSF; PIRSF001558; GSHase; 1. DR SUPFAM; SSF56059; Glutathione synthetase ATP-binding domain-like; 1. DR SUPFAM; SSF52440; PreATP-grasp domain; 1. DR Genevisible; P51855; MM. PE 1: Evidence at protein level; KW Acetylation; ATP-binding; Glutathione biosynthesis; Ligase; Magnesium; KW Metal-binding; Nucleotide-binding; Phosphoprotein; Reference proteome. FT INIT_MET 1 FT /note="Removed" FT /evidence="ECO:0000250|UniProtKB:P48637" FT CHAIN 2..474 FT /note="Glutathione synthetase" FT /id="PRO_0000211262" FT BINDING 125 FT /ligand="substrate" FT /evidence="ECO:0000250" FT BINDING 144 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000250" FT BINDING 144 FT /ligand="Mg(2+)" FT /ligand_id="ChEBI:CHEBI:18420" FT /evidence="ECO:0000250" FT BINDING 146 FT /ligand="Mg(2+)" FT /ligand_id="ChEBI:CHEBI:18420" FT /evidence="ECO:0000250" FT BINDING 148..151 FT /ligand="substrate" FT /evidence="ECO:0000250" FT BINDING 214..216 FT /ligand="substrate" FT /evidence="ECO:0000250" FT BINDING 220 FT /ligand="substrate" FT /evidence="ECO:0000250" FT BINDING 267..270 FT /ligand="substrate" FT /evidence="ECO:0000250" FT BINDING 305 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000250" FT BINDING 364..373 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000250" FT BINDING 368 FT /ligand="Mg(2+)" FT /ligand_id="ChEBI:CHEBI:18420" FT /evidence="ECO:0000250" FT BINDING 375 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000250" FT BINDING 398..401 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000250" FT BINDING 425 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000250" FT BINDING 450 FT /ligand="substrate" FT /evidence="ECO:0000250" FT BINDING 452 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000250" FT BINDING 458 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000250" FT BINDING 461..462 FT /ligand="substrate" FT /evidence="ECO:0000250" FT MOD_RES 2 FT /note="N-acetylalanine" FT /evidence="ECO:0000250|UniProtKB:P48637" FT MOD_RES 415 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:P48637" SQ SEQUENCE 474 AA; 52247 MW; E1302C5B2C28A43A CRC64; MATSWGSILQ DEKQLEELAK QAIDRALAEG VLLRSAQHPS SSDVVTYAPF TLFPSPVPSA LLEQAYAVQM DFNILVDAVS QNPAFLEQTL SSTIKKDDYT ARLFDIYKQV LKEGIAQTVF LGLNRSDYMF QCGADGSKAL KQIEINTISA SFGGLASRTP AVHRHVLNVL NKTKEASKIL SNNPSKGLAL GIAKAWELYG SANAVVLLIA QEKERNIFDQ RAVENELLDR KIHVIRGRFE DVSERGSLDQ NRRLFMDDQE VAVVYFRDGY MPSQYNSQNW EARLMLERSR AAKCPDIAIQ LAGTKKVQQE LSRVGLLEAL LPGQPEAVAR LRATFAGLYS LDMGEEGDQA IAEALAAPSH FVLKPQREGG GNNLYGEEMV QALEQLKDSE ERASYILMEK IEPEPFRNCL LRPGSPAQVV QCISELGIFG VYVRQGTTLV MNKHVGHLLR TKAVEHADGG VAAGVAVLDN PYPV //