GSHB_RAT
ID GSHB_RAT Reviewed; 474 AA.
AC P46413;
DT 01-NOV-1995, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1995, sequence version 1.
DT 03-AUG-2022, entry version 148.
DE RecName: Full=Glutathione synthetase {ECO:0000303|PubMed:7862666};
DE Short=GSH synthetase;
DE Short=GSH-S;
DE EC=6.3.2.3 {ECO:0000269|PubMed:7862666};
DE AltName: Full=Glutathione synthase;
GN Name=Gss;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], PARTIAL PROTEIN SEQUENCE, FUNCTION, CATALYTIC
RP ACTIVITY, AND PATHWAY.
RC TISSUE=Kidney;
RX PubMed=7862666; DOI=10.1073/pnas.92.4.1232;
RA Huang C.-S., He W., Meister A., Anderson M.E.;
RT "Amino acid sequence of rat kidney glutathione synthetase.";
RL Proc. Natl. Acad. Sci. U.S.A. 92:1232-1236(1995).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Kidney;
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).
CC -!- FUNCTION: Catalyzes the production of glutathione from gamma-
CC glutamylcysteine and glycine in an ATP-dependent manner
CC (PubMed:7862666). Glutathione (gamma-glutamylcysteinylglycine, GSH) is
CC the most abundant intracellular thiol in living aerobic cells and is
CC required for numerous processes including the protection of cells
CC against oxidative damage, amino acid transport, the detoxification of
CC foreign compounds, the maintenance of protein sulfhydryl groups in a
CC reduced state and acts as a cofactor for a number of enzymes
CC (PubMed:7862666). {ECO:0000269|PubMed:7862666,
CC ECO:0000303|PubMed:7862666}.
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:0000269|PubMed:7862666};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:13558;
CC Evidence={ECO:0000305|PubMed:7862666};
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:0000305|PubMed:7862666}.
CC -!- SUBUNIT: Homodimer. {ECO:0000250|UniProtKB:P48637}.
CC -!- SIMILARITY: Belongs to the eukaryotic GSH synthase family.
CC {ECO:0000305}.
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DR EMBL; L38615; AAA64618.1; -; mRNA.
DR EMBL; BC078700; AAH78700.1; -; mRNA.
DR PIR; I59346; I59346.
DR RefSeq; NP_037094.1; NM_012962.1.
DR AlphaFoldDB; P46413; -.
DR SMR; P46413; -.
DR STRING; 10116.ENSRNOP00000025657; -.
DR iPTMnet; P46413; -.
DR PhosphoSitePlus; P46413; -.
DR jPOST; P46413; -.
DR PaxDb; P46413; -.
DR PRIDE; P46413; -.
DR Ensembl; ENSRNOT00000025657; ENSRNOP00000025657; ENSRNOG00000018964.
DR GeneID; 25458; -.
DR KEGG; rno:25458; -.
DR UCSC; RGD:2752; rat.
DR CTD; 2937; -.
DR RGD; 2752; Gss.
DR eggNOG; KOG0021; Eukaryota.
DR GeneTree; ENSGT00390000013764; -.
DR HOGENOM; CLU_025152_2_1_1; -.
DR InParanoid; P46413; -.
DR OMA; NGLVMYP; -.
DR OrthoDB; 1189955at2759; -.
DR PhylomeDB; P46413; -.
DR TreeFam; TF105187; -.
DR BRENDA; 6.3.2.3; 5301.
DR Reactome; R-RNO-174403; Glutathione synthesis and recycling.
DR UniPathway; UPA00142; UER00210.
DR PRO; PR:P46413; -.
DR Proteomes; UP000002494; Chromosome 3.
DR Bgee; ENSRNOG00000018964; Expressed in kidney and 20 other tissues.
DR Genevisible; P46413; RN.
DR GO; GO:0005829; C:cytosol; IDA:RGD.
DR GO; GO:0005524; F:ATP binding; IDA:RGD.
DR GO; GO:0043295; F:glutathione binding; IDA:RGD.
DR GO; GO:0004363; F:glutathione synthase activity; IDA:RGD.
DR GO; GO:0016594; F:glycine binding; IDA:RGD.
DR GO; GO:0042802; F:identical protein binding; IPI:RGD.
DR GO; GO:0000287; F:magnesium ion binding; ISS:UniProtKB.
DR GO; GO:0042277; F:peptide binding; IPI:RGD.
DR GO; GO:0042803; F:protein homodimerization activity; ISS:UniProtKB.
DR GO; GO:0007568; P:aging; IEP:RGD.
DR GO; GO:0006750; P:glutathione biosynthetic process; IDA:RGD.
DR GO; GO:0043200; P:response to amino acid; IEP:RGD.
DR GO; GO:0046686; P:response to cadmium ion; ISO:RGD.
DR GO; GO:0031667; P:response to nutrient levels; IEP:RGD.
DR GO; GO:0034612; P:response to tumor necrosis factor; IEP:RGD.
DR GO; GO:0009410; P:response to xenobiotic stimulus; IEP:RGD.
DR CDD; cd00228; eu-GS; 1.
DR Gene3D; 1.10.1080.10; -; 1.
DR Gene3D; 3.30.1490.50; -; 1.
DR Gene3D; 3.30.1490.80; -; 1.
DR Gene3D; 3.40.50.1760; -; 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 PANTHER; PTHR11130; PTHR11130; 1.
DR Pfam; PF03917; GSH_synth_ATP; 1.
DR Pfam; PF03199; GSH_synthase; 1.
DR PIRSF; PIRSF001558; GSHase; 1.
DR SUPFAM; SSF52440; SSF52440; 1.
DR TIGRFAMs; TIGR01986; glut_syn_euk; 1.
PE 1: Evidence at protein level;
KW Acetylation; ATP-binding; Direct protein sequencing;
KW Glutathione biosynthesis; Ligase; Magnesium; Metal-binding;
KW 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_0000211263"
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; 52345 MW; 962B742FD19851A4 CRC64;
MATSWGSILQ DEKQLEELAQ QAIDRALAEG VLLRSAKNPS SSDVVTYAPF TLFPSPVPST
LLEQAYAVQM DFNILVDAVS QNSAFLEQTL SSTIKKDEYT ARLFDIYKQV LKEGIAQTVF
LGLNRSDYMF QCSADGSKAL KQIEINTISA SFGGLASRTP AVHRHVLNVL NKTNEASKIL
SNNPSKGLAL GIAKAWELYG SANAVVLLIA QEKERNIFDQ RAIENELLDR KIHVIRRRFE
DVSERGSLDQ NRRLFMEDQE VAVVYFRDGY MPSQYNAQNW EARLLLERSC AAKCPDIATQ
LAGTKKVQQE LSRVGLLEAL LPGQPEAVAR LRATFAGLYS LDMGEEGDQA VAEALAAPSH
FVLKPQREGG GNNFYGEEMV HALEQLKDSE ERASYILMEK IEPEPFRNCL LRPGSPAQVV
QCISELGIFG VYVRQGTTLV MNKHVGHLLR TKAIEHADGG VAAGVAVLDN PYPV
