MGST1_RAT
ID MGST1_RAT Reviewed; 155 AA.
AC P08011;
DT 01-AUG-1988, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 3.
DT 03-AUG-2022, entry version 158.
DE RecName: Full=Microsomal glutathione S-transferase 1;
DE Short=Microsomal GST-1;
DE EC=2.5.1.18;
DE AltName: Full=Microsomal GST-I;
GN Name=Mgst1; Synonyms=Gst12;
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=3372534; DOI=10.1016/s0021-9258(18)68495-9;
RA Dejong J.L., Morgenstern R., Joernvall H., Depierre J.W., Tu C.-P.D.;
RT "Gene expression of rat and human microsomal glutathione S-transferases.";
RL J. Biol. Chem. 263:8430-8436(1988).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Pituitary;
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 PROTEIN SEQUENCE OF 2-155.
RX PubMed=3932348; DOI=10.1016/s0021-9258(17)38671-4;
RA Morgenstern R., Depierre J.W., Joernvall H.;
RT "Microsomal glutathione transferase. Primary structure.";
RL J. Biol. Chem. 260:13976-13983(1985).
RN [4]
RP SUBCELLULAR LOCATION.
RC STRAIN=Sprague-Dawley; TISSUE=Liver;
RX PubMed=6439207; DOI=10.1016/0006-2952(84)90145-x;
RA Morgenstern R., Lundqvist G., Andersson G., Balk L., Depierre J.W.;
RT "The distribution of microsomal glutathione transferase among different
RT organelles, different organs, and different organisms.";
RL Biochem. Pharmacol. 33:3609-3614(1984).
RN [5]
RP ROLE OF CYS-50 IN ACTIVITY REGULATION.
RX PubMed=11106493; DOI=10.1021/bi001764u;
RA Svensson R., Rinaldi R., Swedmark S., Morgenstern R.;
RT "Reactivity of cysteine-49 and its influence on the activation of
RT microsomal glutathione transferase 1: evidence for subunit interaction.";
RL Biochemistry 39:15144-15149(2000).
RN [6]
RP NITRATION AT TYR-93, AND ACTIVITY REGULATION.
RX PubMed=16314419; DOI=10.1074/jbc.m509480200;
RA Ji Y., Neverova I., Van Eyk J.E., Bennett B.M.;
RT "Nitration of tyrosine 92 mediates the activation of rat microsomal
RT glutathione s-transferase by peroxynitrite.";
RL J. Biol. Chem. 281:1986-1991(2006).
RN [7]
RP X-RAY CRYSTALLOGRAPHY (3.2 ANGSTROMS) OF 2-154 IN COMPLEX WITH GLUTATHIONE,
RP SUBUNIT, SUBCELLULAR LOCATION, MEMBRANE TOPOLOGY, MUTAGENESIS OF HIS-76 AND
RP GLU-81, AND GLUTATHIONE BINDING SITES.
RX PubMed=16806268; DOI=10.1016/j.jmb.2006.05.056;
RA Holm P.J., Bhakat P., Jegerschold C., Gyobu N., Mitsuoka K., Fujiyoshi Y.,
RA Morgenstern R., Hebert H.;
RT "Structural basis for detoxification and oxidative stress protection in
RT membranes.";
RL J. Mol. Biol. 360:934-945(2006).
CC -!- FUNCTION: Conjugation of reduced glutathione to a wide number of
CC exogenous and endogenous hydrophobic electrophiles.
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 -!- ACTIVITY REGULATION: Can be activated by reagents that attack Cys-50
CC sulfhydryl, such as N-ethylmaleimide, except in the testis. Activation
CC also occurs via nitration of Tyr-93 by peroxynitrite.
CC {ECO:0000269|PubMed:16314419}.
CC -!- SUBUNIT: Homotrimer; The trimer binds only one molecule of glutathione.
CC {ECO:0000269|PubMed:16806268}.
CC -!- SUBCELLULAR LOCATION: Microsome. Mitochondrion outer membrane;
CC Peripheral membrane protein. Endoplasmic reticulum membrane; Multi-pass
CC membrane protein.
CC -!- TISSUE SPECIFICITY: Highest in the liver, followed by kidney and testis
CC and much lower in seminal vesicles, spleen, lung and brain.
CC -!- PTM: Peroxynitrite induces nitration at Tyr-93 which activates the
CC enzyme. {ECO:0000269|PubMed:16314419}.
CC -!- SIMILARITY: Belongs to the MAPEG family. {ECO:0000305}.
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DR EMBL; J03752; AAA41281.1; -; mRNA.
DR EMBL; BC063150; AAH63150.1; -; mRNA.
DR PIR; A28083; A28083.
DR RefSeq; NP_599176.1; NM_134349.3.
DR PDB; 2H8A; EM; 3.20 A; A=2-155.
DR PDB; 5I9K; EM; 3.50 A; A=1-155.
DR PDB; 5IA9; EM; 3.50 A; A=1-155.
DR PDBsum; 2H8A; -.
DR PDBsum; 5I9K; -.
DR PDBsum; 5IA9; -.
DR AlphaFoldDB; P08011; -.
DR SMR; P08011; -.
DR IntAct; P08011; 1.
DR STRING; 10116.ENSRNOP00000010579; -.
DR ChEMBL; CHEMBL4630811; -.
DR iPTMnet; P08011; -.
DR PhosphoSitePlus; P08011; -.
DR jPOST; P08011; -.
DR PaxDb; P08011; -.
DR PRIDE; P08011; -.
DR Ensembl; ENSRNOT00000010579; ENSRNOP00000010579; ENSRNOG00000007743.
DR GeneID; 171341; -.
DR KEGG; rno:171341; -.
DR UCSC; RGD:70927; rat.
DR CTD; 4257; -.
DR RGD; 70927; Mgst1.
DR eggNOG; ENOG502S0BD; Eukaryota.
DR GeneTree; ENSGT00390000011980; -.
DR HOGENOM; CLU_105467_1_0_1; -.
DR InParanoid; P08011; -.
DR OMA; TFSMAYN; -.
DR OrthoDB; 1591261at2759; -.
DR PhylomeDB; P08011; -.
DR TreeFam; TF105327; -.
DR BRENDA; 2.5.1.18; 5301.
DR Reactome; R-RNO-156590; Glutathione conjugation.
DR Reactome; R-RNO-5423646; Aflatoxin activation and detoxification.
DR Reactome; R-RNO-6798695; Neutrophil degranulation.
DR SABIO-RK; P08011; -.
DR EvolutionaryTrace; P08011; -.
DR PRO; PR:P08011; -.
DR Proteomes; UP000002494; Chromosome 4.
DR Bgee; ENSRNOG00000007743; Expressed in liver and 19 other tissues.
DR ExpressionAtlas; P08011; baseline and differential.
DR Genevisible; P08011; RN.
DR GO; GO:0045177; C:apical part of cell; IDA:RGD.
DR GO; GO:0005783; C:endoplasmic reticulum; IDA:HGNC-UCL.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0016021; C:integral component of membrane; IDA:UniProtKB.
DR GO; GO:0005741; C:mitochondrial outer membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005739; C:mitochondrion; IDA:RGD.
DR GO; GO:0005634; C:nucleus; IDA:RGD.
DR GO; GO:0005778; C:peroxisomal membrane; IDA:RGD.
DR GO; GO:0043295; F:glutathione binding; IDA:UniProtKB.
DR GO; GO:0004602; F:glutathione peroxidase activity; ISO:RGD.
DR GO; GO:0004364; F:glutathione transferase activity; IDA:RGD.
DR GO; GO:0042802; F:identical protein binding; IDA:RGD.
DR GO; GO:0071449; P:cellular response to lipid hydroperoxide; ISO:RGD.
DR GO; GO:0006749; P:glutathione metabolic process; ISO:RGD.
DR GO; GO:0034635; P:glutathione transport; ISO:RGD.
DR GO; GO:0033327; P:Leydig cell differentiation; IEP:RGD.
DR GO; GO:0032496; P:response to lipopolysaccharide; IDA:RGD.
DR GO; GO:0010243; P:response to organonitrogen compound; IDA:RGD.
DR GO; GO:0009410; P:response to xenobiotic stimulus; IDA:RGD.
DR Gene3D; 1.20.120.550; -; 1.
DR InterPro; IPR023352; MAPEG-like_dom_sf.
DR InterPro; IPR001129; Membr-assoc_MAPEG.
DR InterPro; IPR040162; MGST1-like.
DR PANTHER; PTHR10689; PTHR10689; 1.
DR Pfam; PF01124; MAPEG; 1.
DR SUPFAM; SSF161084; SSF161084; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Direct protein sequencing;
KW Endoplasmic reticulum; Membrane; Microsome; Mitochondrion;
KW Mitochondrion outer membrane; Nitration; Reference proteome; Transferase;
KW Transmembrane; Transmembrane helix.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000269|PubMed:3932348"
FT CHAIN 2..155
FT /note="Microsomal glutathione S-transferase 1"
FT /id="PRO_0000217739"
FT TOPO_DOM 3..9
FT /note="Lumenal"
FT TRANSMEM 10..33
FT /note="Helical"
FT TOPO_DOM 34..62
FT /note="Cytoplasmic"
FT TRANSMEM 63..96
FT /note="Helical"
FT TOPO_DOM 97..99
FT /note="Lumenal"
FT TRANSMEM 100..123
FT /note="Helical"
FT TOPO_DOM 124..128
FT /note="Cytoplasmic"
FT TRANSMEM 129..148
FT /note="Helical"
FT TOPO_DOM 149..155
FT /note="Lumenal"
FT BINDING 38
FT /ligand="glutathione"
FT /ligand_id="ChEBI:CHEBI:57925"
FT /evidence="ECO:0000269|PubMed:16806268"
FT BINDING 73
FT /ligand="glutathione"
FT /ligand_id="ChEBI:CHEBI:57925"
FT /evidence="ECO:0000269|PubMed:16806268"
FT BINDING 74
FT /ligand="glutathione"
FT /ligand_id="ChEBI:CHEBI:57925"
FT /evidence="ECO:0000269|PubMed:16806268"
FT BINDING 76
FT /ligand="glutathione"
FT /ligand_id="ChEBI:CHEBI:57925"
FT /evidence="ECO:0000269|PubMed:16806268"
FT BINDING 81
FT /ligand="glutathione"
FT /ligand_id="ChEBI:CHEBI:57925"
FT /evidence="ECO:0000269|PubMed:16806268"
FT BINDING 121
FT /ligand="glutathione"
FT /ligand_id="ChEBI:CHEBI:57925"
FT /evidence="ECO:0000269|PubMed:16806268"
FT SITE 50
FT /note="Activates the enzyme when modified"
FT MOD_RES 42
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q91VS7"
FT MOD_RES 55
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q91VS7"
FT MOD_RES 60
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q91VS7"
FT MOD_RES 93
FT /note="3'-nitrotyrosine"
FT /evidence="ECO:0000269|PubMed:16314419"
FT MUTAGEN 76
FT /note="H->Q: Decreased enzyme activity."
FT /evidence="ECO:0000269|PubMed:16806268"
FT MUTAGEN 81
FT /note="E->Q: Loss of enzyme activity."
FT /evidence="ECO:0000269|PubMed:16806268"
FT CONFLICT 27
FT /note="M -> V (in Ref. 3; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 55
FT /note="K -> G (in Ref. 3; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 68
FT /note="K -> T (in Ref. 3; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 97
FT /note="G -> A (in Ref. 3; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 101
FT /note="S -> P (in Ref. 3; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 134
FT /note="F -> K (in Ref. 3; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 141
FT /note="T -> D (in Ref. 3; AA sequence)"
FT /evidence="ECO:0000305"
FT HELIX 11..24
FT /evidence="ECO:0007829|PDB:2H8A"
FT HELIX 27..30
FT /evidence="ECO:0007829|PDB:2H8A"
FT HELIX 31..33
FT /evidence="ECO:0007829|PDB:2H8A"
FT HELIX 64..81
FT /evidence="ECO:0007829|PDB:2H8A"
FT HELIX 84..92
FT /evidence="ECO:0007829|PDB:2H8A"
FT TURN 93..95
FT /evidence="ECO:0007829|PDB:2H8A"
FT HELIX 103..122
FT /evidence="ECO:0007829|PDB:2H8A"
FT HELIX 127..137
FT /evidence="ECO:0007829|PDB:2H8A"
FT HELIX 139..146
FT /evidence="ECO:0007829|PDB:2H8A"
SQ SEQUENCE 155 AA; 17472 MW; 8FB62EEDF5A74489 CRC64;
MADLKQLMDN EVLMAFTSYA TIILAKMMFL SSATAFQRLT NKVFANPEDC AGFGKGENAK
KFLRTDEKVE RVRRAHLNDL ENIVPFLGIG LLYSLSGPDL STALIHFRIF VGARIYHTIA
YLTPLPQPNR GLAFFVGYGV TLSMAYRLLR SRLYL
