ID GSHB_BOVIN Reviewed; 474 AA. AC Q5EAC2; Q2TBS8; DT 25-JUL-2006, integrated into UniProtKB/Swiss-Prot. DT 15-MAR-2005, sequence version 1. DT 08-NOV-2023, entry version 105. 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 Bos taurus (Bovine). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Laurasiatheria; Artiodactyla; Ruminantia; Pecora; Bovidae; OC Bovinae; Bos. OX NCBI_TaxID=9913; RN [1] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RX PubMed=16305752; DOI=10.1186/1471-2164-6-166; RA Harhay G.P., Sonstegard T.S., Keele J.W., Heaton M.P., Clawson M.L., RA Snelling W.M., Wiedmann R.T., Van Tassell C.P., Smith T.P.L.; RT "Characterization of 954 bovine full-CDS cDNA sequences."; RL BMC Genomics 6:166-166(2005). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC STRAIN=Crossbred X Angus; TISSUE=Liver; RG NIH - Mammalian Gene Collection (MGC) project; RL Submitted (NOV-2005) to the EMBL/GenBank/DDBJ databases. 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 -!- 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; BT020647; AAX08664.1; -; mRNA. DR EMBL; BC109713; AAI09714.1; -; mRNA. DR RefSeq; NP_001015630.1; NM_001015630.1. DR RefSeq; XP_005214785.1; XM_005214728.3. DR AlphaFoldDB; Q5EAC2; -. DR SMR; Q5EAC2; -. DR STRING; 9913.ENSBTAP00000004559; -. DR PaxDb; 9913-ENSBTAP00000004559; -. DR PeptideAtlas; Q5EAC2; -. DR GeneID; 525059; -. DR KEGG; bta:525059; -. DR CTD; 2937; -. DR eggNOG; KOG0021; Eukaryota. DR HOGENOM; CLU_025152_2_1_1; -. DR InParanoid; Q5EAC2; -. DR TreeFam; TF105187; -. DR UniPathway; UPA00142; UER00210. DR Proteomes; UP000009136; Unplaced. 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; IBA:GO_Central. 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 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_0000247549" 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" FT CONFLICT 238 FT /note="K -> R (in Ref. 2; AAI09714)" FT /evidence="ECO:0000305" SQ SEQUENCE 474 AA; 52066 MW; 964C08AF6A93FFF8 CRC64; MATGWGSLLQ DEQQLEELAR QAVDRALAEG VLLRTSQAPS SSHVVSYAPF TLFPSPVPSA LLEQAYAVQA DFNLLVDAVS QNAVFLEQTL SSTIKRDSFT ARLFDIHKQV LKEGIAQTVF LGLNRSDYMF QCNPDGSAAL KQIEINTVSA SFGGLASRTP AVHRHVLSVL GKTKEAAKIL SNNPSKGLAM GIAKAWELYG SANAQVLLIA QEKERNIFDQ RAIENELLAR NIHVIRRKFE DVSEKGSLDQ DRRLFMDGQE IAVVYFRDGY MPGHYSLQNW EARLLLERSC AVKCPDIATQ LAGTKKVQQE LSRVGVLESF LPGQPEAVAR LRATFAGLYS LDLGEEGDQA ITKAIAAPSC FVLKPQREGG GNNLYGEEMV QALERLKDSE ERASYILMEK IEPEPFRNCL LRPGSPARVI QCISELGIFG VYVREGKTLV MNKHVGHLLR TKAIEHADGG VAAGVAVLDN PYPV //