ID   MGST2_MOUSE             Reviewed;         147 AA.
AC   A2RST1;
DT   17-JUN-2020, integrated into UniProtKB/Swiss-Prot.
DT   06-MAR-2007, sequence version 1.
DT   02-SEP-2026, entry version 130.
DE   RecName: Full=Microsomal glutathione S-transferase 2;
DE            Short=Microsomal GST-2;
DE            EC=2.5.1.18 {ECO:0000250|UniProtKB:Q99735};
DE   AltName: Full=Glutathione peroxidase MGST2;
DE            EC=1.11.1.- {ECO:0000250|UniProtKB:Q99735};
DE   AltName: Full=Leukotriene C4 synthase MGST2;
DE            EC=4.4.1.20 {ECO:0000250|UniProtKB:Q99735};
DE   AltName: Full=Microsomal glutathione S-transferase II;
DE            Short=Microsomal GST-II;
GN   Name=Mgst2 {ECO:0000312|MGI:MGI:2448481}; Synonyms=Gst2;
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 [LARGE SCALE GENOMIC DNA].
RC   STRAIN=C57BL/6J;
RX   PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA   Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA   Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA   Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA   Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA   Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA   Eichler E.E., Ponting C.P.;
RT   "Lineage-specific biology revealed by a finished genome assembly of the
RT   mouse.";
RL   PLoS Biol. 7:E1000112-E1000112(2009).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   TISSUE=Testis;
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   DISRUPTION PHENOTYPE, AND FUNCTION.
RX   PubMed=26656251; DOI=10.1038/ncomms10112;
RA   Dvash E., Har-Tal M., Barak S., Meir O., Rubinstein M.;
RT   "Leukotriene C4 is the major trigger of stress-induced oxidative DNA
RT   damage.";
RL   Nat. Commun. 6:10112-10112(2015).
CC   -!- FUNCTION: Catalyzes several different glutathione-dependent reactions.
CC       Catalyzes the glutathione-dependent reduction of lipid hydroperoxides,
CC       such as 5-HPETE. Has glutathione transferase activity, toward
CC       xenobiotic electrophiles, such as 1-chloro-2, 4-dinitrobenzene (CDNB).
CC       Also catalyzes the conjugation of leukotriene A4 with reduced
CC       glutathione to form leukotriene C4 (LTC4) (By similarity). Involved in
CC       oxidative DNA damage induced by ER stress and anticancer agents by
CC       activating LTC4 biosynthetic machinery in nonimmune cells
CC       (PubMed:26656251). {ECO:0000250|UniProtKB:Q99735,
CC       ECO:0000269|PubMed:26656251}.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=RX + glutathione = an S-substituted glutathione + a halide
CC         anion + 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:0000250|UniProtKB:Q99735};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=1-chloro-2,4-dinitrobenzene + glutathione = 2,4-dinitrophenyl-
CC         S-glutathione + chloride + H(+); Xref=Rhea:RHEA:51220,
CC         ChEBI:CHEBI:15378, ChEBI:CHEBI:17996, ChEBI:CHEBI:34718,
CC         ChEBI:CHEBI:57925, ChEBI:CHEBI:133977; EC=2.5.1.18;
CC         Evidence={ECO:0000250|UniProtKB:Q99735};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=leukotriene C4 = leukotriene A4 + glutathione;
CC         Xref=Rhea:RHEA:17617, ChEBI:CHEBI:57463, ChEBI:CHEBI:57925,
CC         ChEBI:CHEBI:57973; EC=4.4.1.20;
CC         Evidence={ECO:0000250|UniProtKB:Q99735};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=(5S)-hydroperoxy-(6E,8Z,11Z,14Z)-eicosatetraenoate + 2
CC         glutathione = (5S)-hydroxy-(6E,8Z,11Z,14Z)-eicosatetraenoate +
CC         glutathione disulfide + H2O; Xref=Rhea:RHEA:48620, ChEBI:CHEBI:15377,
CC         ChEBI:CHEBI:57450, ChEBI:CHEBI:57925, ChEBI:CHEBI:58297,
CC         ChEBI:CHEBI:90632; Evidence={ECO:0000250|UniProtKB:Q99735};
CC   -!- ACTIVITY REGULATION: Each monomer binds on GSH molecule but only one
CC       subunit is catalytically active. {ECO:0000250|UniProtKB:Q99735}.
CC   -!- SUBUNIT: Homotrimer. {ECO:0000250|UniProtKB:Q99735}.
CC   -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
CC       {ECO:0000250|UniProtKB:Q99735}; Multi-pass membrane protein
CC       {ECO:0000255}. Microsome membrane {ECO:0000250|UniProtKB:Q99735};
CC       Multi-pass membrane protein {ECO:0000255}.
CC   -!- DISRUPTION PHENOTYPE: Deficient mice display resistance to induced ER
CC       stress with reduced cell death and mortality.
CC       {ECO:0000269|PubMed:26656251}.
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DR   EMBL; AC102860; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; AC116729; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; BC132234; AAI32235.1; -; mRNA.
DR   EMBL; BC132260; AAI32261.1; -; mRNA.
DR   CCDS; CCDS38428.1; -.
DR   RefSeq; NP_778160.2; NM_174995.3.
DR   AlphaFoldDB; A2RST1; -.
DR   SMR; A2RST1; -.
DR   FunCoup; A2RST1; 439.
DR   STRING; 10090.ENSMUSP00000096705; -.
DR   PhosphoSitePlus; A2RST1; -.
DR   PaxDb; 10090-ENSMUSP00000096705; -.
DR   ProteomicsDB; 337268; -.
DR   Pumba; A2RST1; -.
DR   Antibodypedia; 2759; 172 antibodies from 29 providers.
DR   DNASU; 211666; -.
DR   Ensembl; ENSMUST00000099106.10; ENSMUSP00000096705.4; ENSMUSG00000074604.10.
DR   GeneID; 211666; -.
DR   KEGG; mmu:211666; -.
DR   UCSC; uc008ped.1; mouse.
DR   AGR; MGI:2448481; -.
DR   CTD; 4258; -.
DR   MGI; MGI:2448481; Mgst2.
DR   VEuPathDB; HostDB:ENSMUSG00000074604; -.
DR   eggNOG; ENOG502S082; Eukaryota.
DR   GeneTree; ENSGT00940000160288; -.
DR   HOGENOM; CLU_110291_3_0_1; -.
DR   InParanoid; A2RST1; -.
DR   OMA; HKYFWGY; -.
DR   OrthoDB; 410651at2759; -.
DR   PhylomeDB; A2RST1; -.
DR   Reactome; R-MMU-156590; Glutathione conjugation.
DR   Reactome; R-MMU-5423646; Aflatoxin activation and detoxification.
DR   BioGRID-ORCS; 211666; 0 hits in 79 CRISPR screens.
DR   PRO; PR:A2RST1; -.
DR   Proteomes; UP000000589; Chromosome 3.
DR   RNAct; A2RST1; protein.
DR   Bgee; ENSMUSG00000074604; Expressed in mucosa of stomach and 131 other cell types or tissues.
DR   ExpressionAtlas; A2RST1; baseline and differential.
DR   GO; GO:0005783; C:endoplasmic reticulum; ISO:GO_Central.
DR   GO; GO:0005789; C:endoplasmic reticulum membrane; ISS:UniProtKB.
DR   GO; GO:0016020; C:membrane; ISO:GO_Central.
DR   GO; GO:0005635; C:nuclear envelope; IBA:GO_Central.
DR   GO; GO:0005886; C:plasma membrane; ISO:GO_Central.
DR   GO; GO:0008047; F:enzyme activator activity; IEA:InterPro.
DR   GO; GO:0043295; F:glutathione binding; ISS:UniProtKB.
DR   GO; GO:0004602; F:glutathione peroxidase activity; ISS:UniProtKB.
DR   GO; GO:0004364; F:glutathione transferase activity; ISS:UniProtKB.
DR   GO; GO:0042802; F:identical protein binding; ISS:UniProtKB.
DR   GO; GO:0004464; F:leukotriene-C4 synthase activity; ISS:UniProtKB.
DR   GO; GO:0047066; F:phospholipid-hydroperoxide glutathione peroxidase activity; IEA:RHEA.
DR   GO; GO:0006750; P:glutathione biosynthetic process; ISO:GO_Central.
DR   GO; GO:0019370; P:leukotriene biosynthetic process; ISS:UniProtKB.
DR   GO; GO:0016042; P:lipid catabolic process; ISO:GO_Central.
DR   GO; GO:0006629; P:lipid metabolic process; ISS:UniProtKB.
DR   GO; GO:0032496; P:response to lipopolysaccharide; IEA:Ensembl.
DR   FunFam; 1.20.120.550:FF:000003; Leukotriene C4 synthase; 1.
DR   Gene3D; 1.20.120.550; Membrane associated eicosanoid/glutathione metabolism-like domain; 1.
DR   InterPro; IPR001446; 5_LipOase_AP.
DR   InterPro; IPR050997; MAPEG.
DR   InterPro; IPR023352; MAPEG-like_dom_sf.
DR   InterPro; IPR001129; Membr-assoc_MAPEG.
DR   PANTHER; PTHR10250; MICROSOMAL GLUTATHIONE S-TRANSFERASE; 1.
DR   PANTHER; PTHR10250:SF13; MICROSOMAL GLUTATHIONE S-TRANSFERASE 2; 1.
DR   Pfam; PF01124; MAPEG; 1.
DR   PRINTS; PR00488; 5LPOXGNASEAP.
DR   SUPFAM; SSF161084; MAPEG domain-like; 1.
PE   2: Evidence at transcript level;
KW   Endoplasmic reticulum; Leukotriene biosynthesis; Lipid metabolism; Lyase;
KW   Membrane; Microsome; Oxidoreductase; Reference proteome; Transferase;
KW   Transmembrane; Transmembrane helix.
FT   CHAIN           1..147
FT                   /note="Microsomal glutathione S-transferase 2"
FT                   /id="PRO_0000449878"
FT   TRANSMEM        6..26
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        62..82
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        107..127
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
SQ   SEQUENCE   147 AA;  16786 MW;  57CFDC147DDF85E4 CRC64;
     MAGDSSLLAA VSLLSACQQS YFAWRVGRAR LKHKIAPPAV TGPLEFERIF RAQQNSLEFY
     PVFIVMLWMA GWYFNQVFAA CLGLLYIYAR HKYFWGYAEA AEKRITGFRL SLGILTLLPV
     LAVLGVASRF LNEYLDFHVA KKLRKPF
//