ID GSHB_XENLA Reviewed; 474 AA. AC P35668; DT 01-JUN-1994, integrated into UniProtKB/Swiss-Prot. DT 01-JUN-1994, sequence version 1. DT 27-MAR-2024, entry version 112. DE RecName: Full=Glutathione synthetase {ECO:0000250|UniProtKB:P48637}; 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:0000250|UniProtKB:P48637}; OS Xenopus laevis (African clawed frog). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Amphibia; OC Batrachia; Anura; Pipoidea; Pipidae; Xenopodinae; Xenopus; Xenopus. OX NCBI_TaxID=8355; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA]. RX PubMed=7916638; DOI=10.1016/0167-4781(93)90202-o; RA Habenicht A., Hille S., Knoechel W.; RT "Molecular cloning of the large subunit of glutathione synthetase from RT Xenopus laevis embryos."; RL Biochim. Biophys. Acta 1174:295-298(1993). 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 (By similarity). CC {ECO:0000250|UniProtKB:P48637, ECO:0000250|UniProtKB:P51855}. 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:0000250|UniProtKB:P51855}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:72076; CC Evidence={ECO:0000250|UniProtKB:P51855}; 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 -!- TISSUE SPECIFICITY: Expressed ubiquitously. 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; X69662; CAA49351.1; -; mRNA. DR PIR; S38333; S38333. DR RefSeq; NP_001081013.1; NM_001087544.1. DR AlphaFoldDB; P35668; -. DR SMR; P35668; -. DR DNASU; 394329; -. DR GeneID; 394329; -. DR KEGG; xla:394329; -. DR AGR; Xenbase:XB-GENE-6254454; -. DR CTD; 394329; -. DR Xenbase; XB-GENE-6254454; gss.L. DR OrthoDB; 1448at2759; -. DR UniPathway; UPA00142; UER00210. DR Proteomes; UP000186698; Chromosome 9_10L. DR Bgee; 394329; Expressed in muscle tissue and 19 other cell types or tissues. 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; IEA:UniProtKB-EC. DR GO; GO:0000287; F:magnesium ion binding; ISS:UniProtKB. DR GO; GO:0042803; F:protein homodimerization activity; ISS:UniProtKB. 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. PE 2: Evidence at transcript level; KW ATP-binding; Glutathione biosynthesis; Ligase; Magnesium; Metal-binding; KW Nucleotide-binding; Reference proteome. FT CHAIN 1..474 FT /note="Glutathione synthetase" FT /id="PRO_0000211264" 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" SQ SEQUENCE 474 AA; 53584 MW; 52CAA42C44079702 CRC64; MADLWDDIYN DTKLLEELAP IAIDAALLQG VLMRTKESPN SSDVVSFAPF ALLPSPVPKA LFEQAKCVQE DFNTLVDRIS QDTSFLEQVL SSTIKVDDFI RRLFAIHKQV QQEDCTQEVF LGINRSDYMF DCRDDGTPAL KQIEINTIAA SFGGLASRTP AVHQHVLKFL RKSEESSSIL TNDAVEGIGW GIAHAWALYG SVDATVMFLV ENEQRNILDQ RFIEAELCKR NVRVIRRRLA DVFERGTLDE ERHLFIDGYE VAVAYFRTGY VPQDYTEQDW EARLMLERSR AVKCPDVPTQ LVGTKKVQQE LSRPQILEKF LPDKPEAVAR IRETFTGLYS LDIGEEGDEA VRVALANPDQ FVLKPQREGG GNNLYGEELK EKLQECKDSE ERTSYILMDK INPKPLKNCL LRAGGRVQIS ECISELGMFG VYVRHRDQMI YYDQVGHLLR TKAIEHSDGG VAAGVAVLDN PYLV //