ID   GSTA3_MOUSE             Reviewed;         221 AA.
AC   P30115; Q544Y6;
DT   01-APR-1993, integrated into UniProtKB/Swiss-Prot.
DT   23-JAN-2007, sequence version 2.
DT   24-JAN-2024, entry version 187.
DE   RecName: Full=Glutathione S-transferase A3 {ECO:0000305};
DE            EC=2.5.1.18;
DE   AltName: Full=GST class-alpha member 3;
DE   AltName: Full=Glutathione S-transferase Ya3;
DE   AltName: Full=Glutathione S-transferase Yc;
GN   Name=Gsta3 {ECO:0000312|MGI:MGI:95856}; Synonyms=Gstyc;
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 [MRNA], AND FUNCTION.
RC   STRAIN=BALB/cJ; TISSUE=Liver;
RX   PubMed=1637297; DOI=10.1042/bj2850173;
RA   Hayes J.D., Judah D.J., Neal G.E., Nguyen T.;
RT   "Molecular cloning and heterologous expression of a cDNA encoding a mouse
RT   glutathione S-transferase Yc subunit possessing high catalytic activity for
RT   aflatoxin B1-8,9-epoxide.";
RL   Biochem. J. 285:173-180(1992).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RC   STRAIN=BALB/cJ; TISSUE=Liver;
RX   PubMed=1728405;
RA   Buetler T.M., Eaton D.L.;
RT   "Complementary DNA cloning, messenger RNA expression, and induction of
RT   alpha-class glutathione S-transferases in mouse tissues.";
RL   Cancer Res. 52:314-318(1992).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   STRAIN=C57BL/6J; TISSUE=Head, and Liver;
RX   PubMed=16141072; DOI=10.1126/science.1112014;
RA   Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA   Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA   Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA   Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA   Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA   Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA   Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA   Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA   Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA   Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA   Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA   Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA   Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA   Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA   Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA   Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA   Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA   Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA   Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA   Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA   Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA   Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA   Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA   Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA   Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA   van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA   Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA   Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA   Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA   Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA   Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA   Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA   Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA   Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT   "The transcriptional landscape of the mammalian genome.";
RL   Science 309:1559-1563(2005).
RN   [4]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA   Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.;
RL   Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN   [5]
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   [6]
RP   PROTEIN SEQUENCE OF 16-56; 63-73; 94-110 AND 112-142.
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   [7]
RP   CHARACTERIZATION, MASS SPECTROMETRY, AND ACETYLATION AT ALA-2.
RC   STRAIN=CD-1; TISSUE=Liver;
RX   PubMed=8605288; DOI=10.1021/tx00050a009;
RA   Mitchell A.E., Morin D., Lame M.W., Jones A.D.;
RT   "Purification, mass spectrometric characterization, and covalent
RT   modification of murine glutathione S-transferases.";
RL   Chem. Res. Toxicol. 8:1054-1062(1995).
RN   [8]
RP   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   TISSUE=Kidney, Liver, Lung, and Spleen;
RX   PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA   Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA   Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT   "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL   Cell 143:1174-1189(2010).
RN   [9]
RP   ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, SUCCINYLATION [LARGE SCALE
RP   ANALYSIS] AT LYS-4, CLEAVAGE OF INITIATOR METHIONINE [LARGE SCALE
RP   ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   TISSUE=Liver;
RX   PubMed=23806337; DOI=10.1016/j.molcel.2013.06.001;
RA   Park J., Chen Y., Tishkoff D.X., Peng C., Tan M., Dai L., Xie Z., Zhang Y.,
RA   Zwaans B.M., Skinner M.E., Lombard D.B., Zhao Y.;
RT   "SIRT5-mediated lysine desuccinylation impacts diverse metabolic
RT   pathways.";
RL   Mol. Cell 50:919-930(2013).
CC   -!- FUNCTION: Conjugation of reduced glutathione to a wide number of
CC       exogenous and endogenous hydrophobic electrophiles. Catalyzes
CC       isomerization reactions that contribute to the biosynthesis of steroid
CC       hormones. Efficiently catalyze obligatory double-bond isomerizations of
CC       delta(5)-androstene-3,17-dione and delta(5)-pregnene-3,20-dione,
CC       precursors to testosterone and progesterone, respectively (By
CC       similarity). Has a high catalytic activity for aflatoxin B1-8,9 epoxide
CC       (PubMed:1637297). {ECO:0000250|UniProtKB:Q16772,
CC       ECO:0000269|PubMed:1637297}.
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:0000250|UniProtKB:Q16772};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:16438;
CC         Evidence={ECO:0000250|UniProtKB:Q16772};
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:Q16772};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:43937;
CC         Evidence={ECO:0000250|UniProtKB:Q16772};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=pregn-5-ene-3,20-dione = progesterone; Xref=Rhea:RHEA:43928,
CC         ChEBI:CHEBI:17026, ChEBI:CHEBI:63837;
CC         Evidence={ECO:0000250|UniProtKB:Q16772};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:43929;
CC         Evidence={ECO:0000250|UniProtKB:Q16772};
CC   -!- SUBUNIT: Homodimer.
CC   -!- SUBCELLULAR LOCATION: Cytoplasm.
CC   -!- MASS SPECTROMETRY: Mass=25271.4; Mass_error=2; Method=Electrospray;
CC       Evidence={ECO:0000269|PubMed:8605288};
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; X65021; CAA46155.1; -; mRNA.
DR   EMBL; M73483; AAA37751.1; -; mRNA.
DR   EMBL; AK014076; BAB29143.1; -; mRNA.
DR   EMBL; AK149543; BAE28948.1; -; mRNA.
DR   EMBL; CH466536; EDL14389.1; -; Genomic_DNA.
DR   EMBL; CH466536; EDL14390.1; -; Genomic_DNA.
DR   EMBL; BC147272; AAI47273.1; -; mRNA.
DR   EMBL; BC147273; AAI47274.1; -; mRNA.
DR   CCDS; CCDS14847.1; -.
DR   PIR; S24322; S24322.
DR   RefSeq; NP_001070821.1; NM_001077353.2.
DR   RefSeq; NP_034486.2; NM_010356.4.
DR   AlphaFoldDB; P30115; -.
DR   SMR; P30115; -.
DR   IntAct; P30115; 1.
DR   STRING; 10090.ENSMUSP00000027067; -.
DR   iPTMnet; P30115; -.
DR   PhosphoSitePlus; P30115; -.
DR   SwissPalm; P30115; -.
DR   CPTAC; non-CPTAC-3324; -.
DR   jPOST; P30115; -.
DR   MaxQB; P30115; -.
DR   PaxDb; 10090-ENSMUSP00000027067; -.
DR   PeptideAtlas; P30115; -.
DR   ProteomicsDB; 271475; -.
DR   Antibodypedia; 30946; 95 antibodies from 19 providers.
DR   DNASU; 14859; -.
DR   Ensembl; ENSMUST00000027067.15; ENSMUSP00000027067.9; ENSMUSG00000025934.16.
DR   Ensembl; ENSMUST00000121676.8; ENSMUSP00000113262.2; ENSMUSG00000025934.16.
DR   GeneID; 14859; -.
DR   KEGG; mmu:14859; -.
DR   UCSC; uc007alk.2; mouse.
DR   AGR; MGI:95856; -.
DR   CTD; 2940; -.
DR   MGI; MGI:95856; Gsta3.
DR   VEuPathDB; HostDB:ENSMUSG00000025934; -.
DR   eggNOG; KOG1695; Eukaryota.
DR   GeneTree; ENSGT00940000163367; -.
DR   HOGENOM; CLU_039475_4_0_1; -.
DR   InParanoid; P30115; -.
DR   OMA; EEYFANM; -.
DR   OrthoDB; 3412208at2759; -.
DR   PhylomeDB; P30115; -.
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; 14859; 2 hits in 78 CRISPR screens.
DR   ChiTaRS; Gsta3; mouse.
DR   PRO; PR:P30115; -.
DR   Proteomes; UP000000589; Chromosome 1.
DR   RNAct; P30115; Protein.
DR   Bgee; ENSMUSG00000025934; Expressed in left lobe of liver and 168 other cell types or tissues.
DR   ExpressionAtlas; P30115; baseline and differential.
DR   GO; GO:0005829; C:cytosol; ISO:MGI.
DR   GO; GO:0004364; F:glutathione transferase activity; IMP:MGI.
DR   GO; GO:0046223; P:aflatoxin catabolic process; IMP:MGI.
DR   GO; GO:0006749; P:glutathione metabolic process; ISS:UniProtKB.
DR   GO; GO:0006629; P:lipid metabolic process; IEA:UniProtKB-KW.
DR   GO; GO:0001657; P:ureteric bud development; 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; 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:SF107; GLUTATHIONE S-TRANSFERASE A2; 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.
DR   SWISS-2DPAGE; P30115; -.
DR   Genevisible; P30115; MM.
PE   1: Evidence at protein level;
KW   Acetylation; Cytoplasm; Direct protein sequencing; Lipid metabolism;
KW   Reference proteome; Transferase.
FT   INIT_MET        1
FT                   /note="Removed"
FT                   /evidence="ECO:0000269|PubMed:8605288,
FT                   ECO:0007744|PubMed:23806337"
FT   CHAIN           2..221
FT                   /note="Glutathione S-transferase A3"
FT                   /id="PRO_0000185790"
FT   DOMAIN          3..83
FT                   /note="GST N-terminal"
FT   DOMAIN          85..207
FT                   /note="GST C-terminal"
FT   BINDING         9
FT                   /ligand="glutathione"
FT                   /ligand_id="ChEBI:CHEBI:57925"
FT                   /evidence="ECO:0000250|UniProtKB:P13745"
FT   BINDING         45
FT                   /ligand="glutathione"
FT                   /ligand_id="ChEBI:CHEBI:57925"
FT                   /evidence="ECO:0000250|UniProtKB:P08263"
FT   BINDING         54..55
FT                   /ligand="glutathione"
FT                   /ligand_id="ChEBI:CHEBI:57925"
FT                   /evidence="ECO:0000250|UniProtKB:P30711"
FT   BINDING         67..68
FT                   /ligand="glutathione"
FT                   /ligand_id="ChEBI:CHEBI:57925"
FT                   /evidence="ECO:0000250|UniProtKB:P13745"
FT   MOD_RES         2
FT                   /note="N-acetylalanine"
FT                   /evidence="ECO:0000269|PubMed:8605288,
FT                   ECO:0007744|PubMed:23806337"
FT   MOD_RES         4
FT                   /note="N6-succinyllysine"
FT                   /evidence="ECO:0007744|PubMed:23806337"
SQ   SEQUENCE   221 AA;  25361 MW;  6F7332488794081F CRC64;
     MAGKPVLHYF DGRGRMEPIR WLLAAAGVEF EEKFLKTRDD LARLRSDGSL MFQQVPMVEI
     DGMKLVQTKA ILNYIASKYN LYGKDMKERA IIDMYTEGVA DLEIMILYYP HMPPEEKEAS
     LAKIKEQTRN RYFPAFEKVL KSHGQDYLVG NRLSRADIAL VELLYHVEEL DPGVVDNFPL
     LKALRSRVSN LPTVKKFLQP GSQRKPFDDA KCVESAKKIF S
//