ID GSTA1_RAT Reviewed; 222 AA.
AC P00502; Q6AZ72;
DT 21-JUL-1986, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 3.
DT 27-MAR-2024, entry version 182.
DE RecName: Full=Glutathione S-transferase alpha-1 {ECO:0000305};
DE EC=2.5.1.18 {ECO:0000269|PubMed:11119643};
DE AltName: Full=13-hydroperoxyoctadecadienoate peroxidase {ECO:0000250|UniProtKB:P08263};
DE EC=1.11.1.- {ECO:0000250|UniProtKB:P08263};
DE AltName: Full=Androst-5-ene-3,17-dione isomerase {ECO:0000250|UniProtKB:P08263};
DE EC=5.3.3.- {ECO:0000250|UniProtKB:P08263};
DE AltName: Full=GST 1-1;
DE AltName: Full=GST 1a-1a;
DE AltName: Full=GST A1-1;
DE AltName: Full=GST B;
DE AltName: Full=Glutathione S-transferase Ya-1;
DE Short=GST Ya1;
DE AltName: Full=Ligandin;
GN Name=Gsta1;
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].
RC STRAIN=Sprague-Dawley; TISSUE=Liver;
RX PubMed=6201485; DOI=10.1016/s0021-9258(18)91046-x;
RA Lai H.-C.J., Li N.-Q., Weiss M.J., Reddy C.C., Tu C.-P.D.;
RT "The nucleotide sequence of a rat liver glutathione S-transferase subunit
RT cDNA clone.";
RL J. Biol. Chem. 259:5536-5542(1984).
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).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 46-197.
RX PubMed=6273441; DOI=10.1016/s0021-9258(19)68395-x;
RA Kalinyak J.E., Taylor J.M.;
RT "Rat glutathione S-transferase. Cloning of double-stranded cDNA and
RT induction of its mRNA.";
RL J. Biol. Chem. 257:523-530(1982).
RN [4]
RP X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS) IN COMPLEX WITH GLUTATHIONE,
RP CATALYTIC ACTIVITY, AND SUBUNIT.
RX PubMed=11119643;
RX DOI=10.1002/1097-0134(20010201)42:2<192::aid-prot60>3.0.co;2-#;
RA Adman E.T., Le Trong I., Stenkamp R.E., Nieslanik B.S., Dietze E.C.,
RA Tai G., Ibarra C., Atkins W.M.;
RT "Localization of the C-terminus of rat glutathione S-transferase A1-1:
RT crystal structure of mutants W21F and W21F/F220Y.";
RL Proteins 42:192-200(2001).
CC -!- FUNCTION: Glutathione S-transferase that catalyzes the nucleophilic
CC attack of the sulfur atom of glutathione on the electrophilic groups of
CC a wide range of exogenous and endogenous compounds (Probable). Involved
CC in the formation of glutathione conjugates of both prostaglandin A2
CC (PGA2) and prostaglandin J2 (PGJ2). It also catalyzes the isomerization
CC of D5-androstene-3,17-dione (AD) into D4-androstene-3,17-dione and may
CC therefore play an important role in hormone biosynthesis. Through its
CC glutathione-dependent peroxidase activity toward the fatty acid
CC hydroperoxide (13S)-hydroperoxy-(9Z,11E)-octadecadienoate/13-HPODE it
CC is also involved in the metabolism of oxidized linoleic acid (By
CC similarity). {ECO:0000250|UniProtKB:P08263,
CC ECO:0000305|PubMed:11119643}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=glutathione + RX = a halide anion + an S-substituted
CC glutathione + H(+); Xref=Rhea:RHEA:16437, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:16042, ChEBI:CHEBI:17792, ChEBI:CHEBI:57925,
CC ChEBI:CHEBI:90779; EC=2.5.1.18;
CC Evidence={ECO:0000269|PubMed:11119643};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:16438;
CC Evidence={ECO:0000305|PubMed:11119643};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=glutathione + prostaglandin A2 = prostaglandin A2-S-(R)-
CC glutathione; Xref=Rhea:RHEA:50796, ChEBI:CHEBI:57925,
CC ChEBI:CHEBI:133370, ChEBI:CHEBI:133768;
CC Evidence={ECO:0000250|UniProtKB:P08263};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:50797;
CC Evidence={ECO:0000250|UniProtKB:P08263};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=glutathione + prostaglandin J2 = prostaglandin J2-S-(R)-
CC glutathione; Xref=Rhea:RHEA:50804, ChEBI:CHEBI:57925,
CC ChEBI:CHEBI:133396, ChEBI:CHEBI:133771;
CC Evidence={ECO:0000250|UniProtKB:P08263};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:50805;
CC Evidence={ECO:0000250|UniProtKB:P08263};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(13S)-hydroperoxy-(9Z,11E)-octadecadienoate + 2 glutathione =
CC (13S)-hydroxy-(9Z,11E)-octadecadienoate + glutathione disulfide +
CC H2O; Xref=Rhea:RHEA:48888, ChEBI:CHEBI:15377, ChEBI:CHEBI:57466,
CC ChEBI:CHEBI:57925, ChEBI:CHEBI:58297, ChEBI:CHEBI:90850;
CC Evidence={ECO:0000250|UniProtKB:P08263};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:48889;
CC Evidence={ECO:0000250|UniProtKB:P08263};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=androst-5-ene-3,17-dione = androst-4-ene-3,17-dione;
CC Xref=Rhea:RHEA:43936, ChEBI:CHEBI:16422, ChEBI:CHEBI:83865;
CC Evidence={ECO:0000250|UniProtKB:P08263};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:43937;
CC Evidence={ECO:0000250|UniProtKB:P08263};
CC -!- SUBUNIT: Homodimer (PubMed:11119643). Homodimer or heterodimer of GSTA1
CC and GSTA2 (By similarity). {ECO:0000250|UniProtKB:P08263,
CC ECO:0000269|PubMed:11119643}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm.
CC -!- MISCELLANEOUS: In addition to its enzymatic activity, the homodimer of
CC Ya chains, called ligandin, binds various organic anions, xenobiotics,
CC and azocarcinogen dyes.
CC -!- SIMILARITY: Belongs to the GST superfamily. Alpha family.
CC {ECO:0000305}.
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DR EMBL; K01931; AAA41283.1; -; mRNA.
DR EMBL; BC078706; AAH78706.1; -; mRNA.
DR PIR; A24735; A24735.
DR PIR; A92479; XURTG.
DR RefSeq; NP_058709.2; NM_017013.4.
DR PDB; 1EV4; X-ray; 2.20 A; A/C/D=2-222.
DR PDB; 1EV9; X-ray; 2.20 A; A/C/D=2-222.
DR PDBsum; 1EV4; -.
DR PDBsum; 1EV9; -.
DR AlphaFoldDB; P00502; -.
DR SMR; P00502; -.
DR IntAct; P00502; 1.
DR ChEMBL; CHEMBL2390; -.
DR iPTMnet; P00502; -.
DR PhosphoSitePlus; P00502; -.
DR Ensembl; ENSRNOT00000032185.6; ENSRNOP00000037786.6; ENSRNOG00000029861.6.
DR Ensembl; ENSRNOT00055007551; ENSRNOP00055005672; ENSRNOG00055004745.
DR Ensembl; ENSRNOT00060035459; ENSRNOP00060029144; ENSRNOG00060020462.
DR Ensembl; ENSRNOT00065028184; ENSRNOP00065022288; ENSRNOG00065016875.
DR GeneID; 24422; -.
DR KEGG; rno:24422; -.
DR AGR; RGD:2754; -.
DR CTD; 2939; -.
DR RGD; 2753; Gsta1.
DR GeneTree; ENSGT00940000154526; -.
DR InParanoid; P00502; -.
DR OMA; RMESIGW; -.
DR OrthoDB; 3412208at2759; -.
DR PhylomeDB; P00502; -.
DR TreeFam; TF105321; -.
DR Reactome; R-RNO-156590; Glutathione conjugation.
DR Reactome; R-RNO-189483; Heme degradation.
DR Reactome; R-RNO-9748787; Azathioprine ADME.
DR EvolutionaryTrace; P00502; -.
DR PRO; PR:P00502; -.
DR Proteomes; UP000002494; Chromosome 8.
DR GO; GO:0005829; C:cytosol; IDA:CAFA.
DR GO; GO:0035731; F:dinitrosyl-iron complex binding; IDA:RGD.
DR GO; GO:0005504; F:fatty acid binding; ISO:RGD.
DR GO; GO:0043295; F:glutathione binding; IDA:CAFA.
DR GO; GO:0004602; F:glutathione peroxidase activity; ISO:RGD.
DR GO; GO:0004364; F:glutathione transferase activity; IDA:CAFA.
DR GO; GO:0042803; F:protein homodimerization activity; IDA:CAFA.
DR GO; GO:0004769; F:steroid delta-isomerase activity; ISS:UniProtKB.
DR GO; GO:0030855; P:epithelial cell differentiation; ISO:RGD.
DR GO; GO:1901687; P:glutathione derivative biosynthetic process; ISS:UniProtKB.
DR GO; GO:0006749; P:glutathione metabolic process; ISO:RGD.
DR GO; GO:0043651; P:linoleic acid metabolic process; ISO:RGD.
DR GO; GO:0006693; P:prostaglandin metabolic process; ISS:UniProtKB.
DR GO; GO:0031667; P:response to nutrient levels; IEP:RGD.
DR GO; GO:0009410; P:response to xenobiotic stimulus; NAS:RGD.
DR GO; GO:0042178; P:xenobiotic catabolic process; IDA:CAFA.
DR GO; GO:0006805; P:xenobiotic metabolic process; IBA:GO_Central.
DR CDD; cd03208; GST_C_Alpha; 1.
DR CDD; cd03077; GST_N_Alpha; 1.
DR Gene3D; 1.20.1050.10; -; 1.
DR Gene3D; 3.40.30.10; Glutaredoxin; 1.
DR InterPro; IPR010987; Glutathione-S-Trfase_C-like.
DR InterPro; IPR036282; Glutathione-S-Trfase_C_sf.
DR InterPro; IPR004045; Glutathione_S-Trfase_N.
DR InterPro; IPR003080; GST_alpha.
DR InterPro; IPR004046; GST_C.
DR InterPro; IPR036249; Thioredoxin-like_sf.
DR PANTHER; PTHR11571; GLUTATHIONE S-TRANSFERASE; 1.
DR PANTHER; PTHR11571:SF233; GLUTATHIONE S-TRANSFERASE-RELATED; 1.
DR Pfam; PF00043; GST_C; 1.
DR Pfam; PF02798; GST_N; 1.
DR PRINTS; PR01266; GSTRNSFRASEA.
DR SFLD; SFLDG01205; AMPS.1; 1.
DR SFLD; SFLDG00363; AMPS_(cytGST):_Alpha-__Mu-__Pi; 1.
DR SUPFAM; SSF47616; GST C-terminal domain-like; 1.
DR SUPFAM; SSF52833; Thioredoxin-like; 1.
DR PROSITE; PS50405; GST_CTER; 1.
DR PROSITE; PS50404; GST_NTER; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Cytoplasm; Isomerase; Lipid metabolism;
KW Oxidoreductase; Peroxidase; Reference proteome; Transferase.
FT CHAIN 1..222
FT /note="Glutathione S-transferase alpha-1"
FT /id="PRO_0000185792"
FT DOMAIN 3..83
FT /note="GST N-terminal"
FT DOMAIN 85..208
FT /note="GST C-terminal"
FT BINDING 9
FT /ligand="glutathione"
FT /ligand_id="ChEBI:CHEBI:57925"
FT /evidence="ECO:0000269|PubMed:11119643"
FT BINDING 45
FT /ligand="glutathione"
FT /ligand_id="ChEBI:CHEBI:57925"
FT /evidence="ECO:0000269|PubMed:11119643"
FT BINDING 54..55
FT /ligand="glutathione"
FT /ligand_id="ChEBI:CHEBI:57925"
FT /evidence="ECO:0000269|PubMed:11119643"
FT BINDING 67..68
FT /ligand="glutathione"
FT /ligand_id="ChEBI:CHEBI:57925"
FT /evidence="ECO:0000269|PubMed:11119643"
FT MOD_RES 1
FT /note="N-acetylmethionine"
FT /evidence="ECO:0000250|UniProtKB:P80894"
FT MOD_RES 4
FT /note="N6-succinyllysine"
FT /evidence="ECO:0000250|UniProtKB:P30115"
FT CONFLICT 152
FT /note="R -> K (in Ref. 1 and 3)"
FT /evidence="ECO:0000305"
FT CONFLICT 208
FT /note="V -> M (in Ref. 1; AAA41283)"
FT /evidence="ECO:0000305"
FT STRAND 6..12
FT /evidence="ECO:0007829|PDB:1EV4"
FT HELIX 16..25
FT /evidence="ECO:0007829|PDB:1EV4"
FT STRAND 31..35
FT /evidence="ECO:0007829|PDB:1EV4"
FT HELIX 38..46
FT /evidence="ECO:0007829|PDB:1EV4"
FT STRAND 57..60
FT /evidence="ECO:0007829|PDB:1EV4"
FT STRAND 63..67
FT /evidence="ECO:0007829|PDB:1EV4"
FT HELIX 68..79
FT /evidence="ECO:0007829|PDB:1EV4"
FT HELIX 86..109
FT /evidence="ECO:0007829|PDB:1EV4"
FT HELIX 114..116
FT /evidence="ECO:0007829|PDB:1EV4"
FT HELIX 117..130
FT /evidence="ECO:0007829|PDB:1EV4"
FT HELIX 132..143
FT /evidence="ECO:0007829|PDB:1EV4"
FT STRAND 146..149
FT /evidence="ECO:0007829|PDB:1EV4"
FT HELIX 155..171
FT /evidence="ECO:0007829|PDB:1EV4"
FT HELIX 172..175
FT /evidence="ECO:0007829|PDB:1EV4"
FT HELIX 179..190
FT /evidence="ECO:0007829|PDB:1EV4"
FT HELIX 192..198
FT /evidence="ECO:0007829|PDB:1EV4"
FT HELIX 211..219
FT /evidence="ECO:0007829|PDB:1EV4"
SQ SEQUENCE 222 AA; 25607 MW; AE43A1BEBE8549CF CRC64;
MSGKPVLHYF NARGRMECIR WLLAAAGVEF DEKFIQSPED LEKLKKDGNL MFDQVPMVEI
DGMKLAQTRA ILNYIATKYD LYGKDMKERA LIDMYTEGIL DLTEMIMQLV ICPPDQKEAK
TALAKDRTKN RYLPAFEKVL KSHGQDYLVG NRLTRVDIHL LELLLYVEEF DASLLTSFPL
LKAFKSRISS LPNVKKFLQP GSQRKLPVDA KQIEEARKIF KF
//
