ID   GSTA1_MOUSE             Reviewed;         223 AA.
AC   P13745; A2RTN4;
DT   01-JAN-1990, integrated into UniProtKB/Swiss-Prot.
DT   23-JAN-2007, sequence version 2.
DT   27-MAR-2024, entry version 185.
DE   RecName: Full=Glutathione S-transferase A1 {ECO:0000305};
DE            EC=2.5.1.18 {ECO:0000269|PubMed:9606968, ECO:0000305|PubMed:11027134};
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 class-alpha member 1;
DE   AltName: Full=Glutathione S-transferase Ya;
DE   AltName: Full=Glutathione S-transferase Ya1;
DE   Contains:
DE     RecName: Full=Glutathione S-transferase A1, N-terminally processed;
GN   Name=Gsta1; Synonyms=Gsta, Gstya;
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 [GENOMIC DNA].
RX   PubMed=3652905; DOI=10.1089/dna.1987.6.317;
RA   Daniel V., Sharon R., Tichauer Y., Sarid S.;
RT   "Mouse glutathione S-transferase Ya subunit: gene structure and sequence.";
RL   DNA 6:317-324(1987).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [MRNA], PROTEIN SEQUENCE, FUNCTION, CATALYTIC ACTIVITY,
RP   BIOPHYSICOCHEMICAL PROPERTIES, AND TISSUE SPECIFICITY.
RX   PubMed=9606968; DOI=10.1006/abbi.1998.0668;
RA   Xia H., Pan S.S., Hu X., Srivastava S.K., Pal A., Singh S.V.;
RT   "Cloning, expression, and biochemical characterization of a functionally
RT   novel alpha class glutathione S-transferase with exceptional activity in
RT   the glutathione conjugation of (+)-anti-7,8-dihydroxy-9,10-oxy-7,8,9,10-
RT   tetrahydrobenzo(a)pyrene.";
RL   Arch. Biochem. Biophys. 353:337-348(1998).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   TISSUE=Brain;
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   [4]
RP   PROTEIN SEQUENCE OF 16-36; 51-59; 63-165 AND 208-223, AND INDUCTION.
RC   TISSUE=Liver;
RX   PubMed=2049074; DOI=10.1042/bj2760461;
RA   McLellan L.I., Kerr L.A., Cronshaw A.D., Hayes J.D.;
RT   "Regulation of mouse glutathione S-transferases by chemoprotectors.
RT   Molecular evidence for the existence of three distinct alpha-class
RT   glutathione S-transferase subunits, Ya1, Ya2, and Ya3, in mouse liver.";
RL   Biochem. J. 276:461-469(1991).
RN   [5]
RP   X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS) IN COMPLEXES WITH GLUTATHIONE AND
RP   SUBSTRATE, FUNCTION, CATALYTIC ACTIVITY, SUBUNIT, AND REGION.
RX   PubMed=11027134; DOI=10.1021/bi001396u;
RA   Gu Y., Singh S.V., Ji X.;
RT   "Residue R216 and catalytic efficiency of a murine class alpha glutathione
RT   S-transferase toward benzo[a]pyrene 7(R),8(S)-diol 9(S), 10(R)-epoxide.";
RL   Biochemistry 39:12552-12557(2000).
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 (PubMed:9606968).
CC       Involved in the formation of glutathione conjugates of both
CC       prostaglandin A2 (PGA2) and prostaglandin J2 (PGJ2). It also catalyzes
CC       the isomerization of D5-androstene-3,17-dione (AD) into D4-androstene-
CC       3,17-dione and may therefore play an important role in hormone
CC       biosynthesis. Through its glutathione-dependent peroxidase activity
CC       toward the fatty acid hydroperoxide (13S)-hydroperoxy-(9Z,11E)-
CC       octadecadienoate/13-HPODE it is also involved in the metabolism of
CC       oxidized linoleic acid (By similarity). {ECO:0000250|UniProtKB:P08263,
CC       ECO:0000269|PubMed:9606968, ECO:0000305|PubMed:11027134}.
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; Evidence={ECO:0000269|PubMed:9606968,
CC         ECO:0000305|PubMed:11027134};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:16438;
CC         Evidence={ECO:0000305|PubMed:11027134};
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   -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC       Kinetic parameters:
CC         KM=35 uM for
CC         7,8-Dihydroxy-9,10-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene
CC         {ECO:0000269|PubMed:9606968};
CC         Vmax=5200 nmol/min/mg enzyme for
CC         7,8-Dihydroxy-9,10-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene
CC         {ECO:0000269|PubMed:9606968};
CC   -!- SUBUNIT: Homodimer. {ECO:0000269|PubMed:11027134}.
CC   -!- TISSUE SPECIFICITY: Expressed in the liver, skin and kidney.
CC       {ECO:0000269|PubMed:9606968}.
CC   -!- INDUCTION: Induced in the liver by beta-naphthoflavone (BNF) and 2(3)-
CC       t-butyl-4-hydroxyanisole (BHA). {ECO:0000269|PubMed:2049074}.
CC   -!- SIMILARITY: Belongs to the GST superfamily. Alpha 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; M19256; AAA37750.1; ALT_SEQ; Genomic_DNA.
DR   EMBL; M19251; AAA37750.1; JOINED; Genomic_DNA.
DR   EMBL; M19252; AAA37750.1; JOINED; Genomic_DNA.
DR   EMBL; M19253; AAA37750.1; JOINED; Genomic_DNA.
DR   EMBL; M19254; AAA37750.1; JOINED; Genomic_DNA.
DR   EMBL; M19255; AAA37750.1; JOINED; Genomic_DNA.
DR   EMBL; BC132572; AAI32573.1; -; mRNA.
DR   EMBL; BC132576; AAI32577.1; -; mRNA.
DR   CCDS; CCDS23358.1; -.
DR   PIR; A27848; A27848.
DR   RefSeq; NP_032207.3; NM_008181.3.
DR   PDB; 1F3A; X-ray; 1.90 A; A/B=2-223.
DR   PDB; 1F3B; X-ray; 2.00 A; A/B=2-223.
DR   PDBsum; 1F3A; -.
DR   PDBsum; 1F3B; -.
DR   AlphaFoldDB; P13745; -.
DR   SMR; P13745; -.
DR   BioGRID; 200090; 2.
DR   STRING; 10090.ENSMUSP00000096139; -.
DR   iPTMnet; P13745; -.
DR   PhosphoSitePlus; P13745; -.
DR   SwissPalm; P13745; -.
DR   jPOST; P13745; -.
DR   MaxQB; P13745; -.
DR   PaxDb; 10090-ENSMUSP00000096139; -.
DR   PeptideAtlas; P13745; -.
DR   ProteomicsDB; 271447; -.
DR   DNASU; 14857; -.
DR   Ensembl; ENSMUST00000098537.4; ENSMUSP00000096139.4; ENSMUSG00000074183.4.
DR   GeneID; 14857; -.
DR   KEGG; mmu:14857; -.
DR   UCSC; uc009qtz.1; mouse.
DR   AGR; MGI:1095417; -.
DR   MGI; MGI:1095417; Gsta1.
DR   VEuPathDB; HostDB:ENSMUSG00000074183; -.
DR   eggNOG; KOG1695; Eukaryota.
DR   GeneTree; ENSGT00940000154526; -.
DR   HOGENOM; CLU_039475_4_0_1; -.
DR   InParanoid; P13745; -.
DR   OMA; RMESIGW; -.
DR   OrthoDB; 3412208at2759; -.
DR   PhylomeDB; P13745; -.
DR   TreeFam; TF105321; -.
DR   Reactome; R-MMU-156590; Glutathione conjugation.
DR   Reactome; R-MMU-189483; Heme degradation.
DR   Reactome; R-MMU-9748787; Azathioprine ADME.
DR   BioGRID-ORCS; 14857; 2 hits in 27 CRISPR screens.
DR   EvolutionaryTrace; P13745; -.
DR   PRO; PR:P13745; -.
DR   Proteomes; UP000000589; Chromosome 9.
DR   RNAct; P13745; Protein.
DR   Bgee; ENSMUSG00000074183; Expressed in duodenum and 55 other cell types or tissues.
DR   GO; GO:0005829; C:cytosol; ISO:MGI.
DR   GO; GO:0035731; F:dinitrosyl-iron complex binding; ISO:MGI.
DR   GO; GO:0005504; F:fatty acid binding; ISO:MGI.
DR   GO; GO:0043295; F:glutathione binding; ISO:MGI.
DR   GO; GO:0004602; F:glutathione peroxidase activity; ISO:MGI.
DR   GO; GO:0004364; F:glutathione transferase activity; IDA:UniProtKB.
DR   GO; GO:0042803; F:protein homodimerization activity; ISO:MGI.
DR   GO; GO:0004769; F:steroid delta-isomerase activity; ISS:UniProtKB.
DR   GO; GO:1901687; P:glutathione derivative biosynthetic process; ISS:UniProtKB.
DR   GO; GO:0006749; P:glutathione metabolic process; ISS:UniProtKB.
DR   GO; GO:0006693; P:prostaglandin metabolic process; ISS:UniProtKB.
DR   GO; GO:0009617; P:response to bacterium; IEP:MGI.
DR   GO; GO:0035634; P:response to stilbenoid; IEP:UniProtKB.
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; IPR040079; Glutathione_S-Trfase.
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; SFLDS00019; Glutathione_Transferase_(cytos; 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.
DR   Genevisible; P13745; MM.
PE   1: Evidence at protein level;
KW   3D-structure; Acetylation; Direct protein sequencing; Isomerase;
KW   Lipid metabolism; Oxidoreductase; Peroxidase; Reference proteome;
KW   Transferase.
FT   CHAIN           1..223
FT                   /note="Glutathione S-transferase A1"
FT                   /id="PRO_0000423204"
FT   INIT_MET        1
FT                   /note="Removed; alternate"
FT                   /evidence="ECO:0000250|UniProtKB:P30115"
FT   CHAIN           2..223
FT                   /note="Glutathione S-transferase A1, N-terminally
FT                   processed"
FT                   /id="PRO_0000185788"
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:0000305|PubMed:11027134"
FT   BINDING         45
FT                   /ligand="glutathione"
FT                   /ligand_id="ChEBI:CHEBI:57925"
FT                   /evidence="ECO:0000269|PubMed:11027134"
FT   BINDING         54..55
FT                   /ligand="glutathione"
FT                   /ligand_id="ChEBI:CHEBI:57925"
FT                   /evidence="ECO:0000269|PubMed:11027134"
FT   BINDING         67..68
FT                   /ligand="glutathione"
FT                   /ligand_id="ChEBI:CHEBI:57925"
FT                   /evidence="ECO:0000269|PubMed:11027134"
FT   MOD_RES         1
FT                   /note="N-acetylmethionine"
FT                   /evidence="ECO:0000250|UniProtKB:P80894"
FT   MOD_RES         2
FT                   /note="N-acetylalanine; in Glutathione S-transferase A1, N-
FT                   terminally processed"
FT                   /evidence="ECO:0000250|UniProtKB:P30115"
FT   MOD_RES         4
FT                   /note="N6-succinyllysine"
FT                   /evidence="ECO:0000250|UniProtKB:P30115"
FT   STRAND          6..12
FT                   /evidence="ECO:0007829|PDB:1F3A"
FT   TURN            14..16
FT                   /evidence="ECO:0007829|PDB:1F3A"
FT   HELIX           17..25
FT                   /evidence="ECO:0007829|PDB:1F3A"
FT   STRAND          31..35
FT                   /evidence="ECO:0007829|PDB:1F3A"
FT   HELIX           38..46
FT                   /evidence="ECO:0007829|PDB:1F3A"
FT   STRAND          57..60
FT                   /evidence="ECO:0007829|PDB:1F3A"
FT   STRAND          63..67
FT                   /evidence="ECO:0007829|PDB:1F3A"
FT   HELIX           68..78
FT                   /evidence="ECO:0007829|PDB:1F3A"
FT   HELIX           86..108
FT                   /evidence="ECO:0007829|PDB:1F3A"
FT   HELIX           109..111
FT                   /evidence="ECO:0007829|PDB:1F3A"
FT   TURN            114..116
FT                   /evidence="ECO:0007829|PDB:1F3A"
FT   HELIX           117..130
FT                   /evidence="ECO:0007829|PDB:1F3A"
FT   HELIX           132..143
FT                   /evidence="ECO:0007829|PDB:1F3A"
FT   STRAND          146..149
FT                   /evidence="ECO:0007829|PDB:1F3A"
FT   HELIX           155..171
FT                   /evidence="ECO:0007829|PDB:1F3A"
FT   HELIX           172..175
FT                   /evidence="ECO:0007829|PDB:1F3A"
FT   HELIX           179..189
FT                   /evidence="ECO:0007829|PDB:1F3A"
FT   HELIX           192..198
FT                   /evidence="ECO:0007829|PDB:1F3A"
FT   HELIX           210..217
FT                   /evidence="ECO:0007829|PDB:1F3A"
SQ   SEQUENCE   223 AA;  25608 MW;  A348A07133FBEC1D CRC64;
     MAGKPVLHYF NARGRMECIR WLLAAAGVEF EEKFIQSPED LEKLKKDGNL MFDQVPMVEI
     DGMKLAQTRA ILNYIATKYD LYGKDMKERA LIDMYSEGIL DLTEMIGQLV LCPPDQREAK
     TALAKDRTKN RYLPAFEKVL KSHGQDYLVG NRLTRVDIHL LEVLLYVEEF DASLLTPFPL
     LKAFKSRISS LPNVKKFLQP GSQRKPPMDA KQIQEARKAF KIQ
//