GSTA3_HUMAN
ID GSTA3_HUMAN Reviewed; 222 AA.
AC Q16772; O43468; Q068V6; Q8WWA8; Q9H415;
DT 15-JUL-1999, integrated into UniProtKB/Swiss-Prot.
DT 27-MAY-2002, sequence version 3.
DT 03-AUG-2022, entry version 189.
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 A3-3;
GN Name=GSTA3 {ECO:0000312|HGNC:HGNC:4628};
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=8307579; DOI=10.1016/s0888-7543(05)80373-8;
RA Suzuki T., Johnston P.N., Board P.G.;
RT "Structure and organization of the human alpha class glutathione S-
RT transferase genes and related pseudogenes.";
RL Genomics 18:680-686(1993).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA], CHARACTERIZATION, CATALYTIC ACTIVITY, FUNCTION,
RP AND BIOPHYSICOCHEMICAL PROPERTIES.
RX PubMed=11418619; DOI=10.1074/jbc.m104539200;
RA Johansson A.-S., Mannervik B.;
RT "Human glutathione transferase A3-3, a highly efficient catalyst of double-
RT bond isomerization in the biosynthetic pathway of steroid hormones.";
RL J. Biol. Chem. 276:33061-33065(2001).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS GLU-36; LEU-71; ASP-73;
RP GLN-113 AND THR-208.
RG NIEHS SNPs program;
RL Submitted (SEP-2006) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=14574404; DOI=10.1038/nature02055;
RA Mungall A.J., Palmer S.A., Sims S.K., Edwards C.A., Ashurst J.L.,
RA Wilming L., Jones M.C., Horton R., Hunt S.E., Scott C.E., Gilbert J.G.R.,
RA Clamp M.E., Bethel G., Milne S., Ainscough R., Almeida J.P., Ambrose K.D.,
RA Andrews T.D., Ashwell R.I.S., Babbage A.K., Bagguley C.L., Bailey J.,
RA Banerjee R., Barker D.J., Barlow K.F., Bates K., Beare D.M., Beasley H.,
RA Beasley O., Bird C.P., Blakey S.E., Bray-Allen S., Brook J., Brown A.J.,
RA Brown J.Y., Burford D.C., Burrill W., Burton J., Carder C., Carter N.P.,
RA Chapman J.C., Clark S.Y., Clark G., Clee C.M., Clegg S., Cobley V.,
RA Collier R.E., Collins J.E., Colman L.K., Corby N.R., Coville G.J.,
RA Culley K.M., Dhami P., Davies J., Dunn M., Earthrowl M.E., Ellington A.E.,
RA Evans K.A., Faulkner L., Francis M.D., Frankish A., Frankland J.,
RA French L., Garner P., Garnett J., Ghori M.J., Gilby L.M., Gillson C.J.,
RA Glithero R.J., Grafham D.V., Grant M., Gribble S., Griffiths C.,
RA Griffiths M.N.D., Hall R., Halls K.S., Hammond S., Harley J.L., Hart E.A.,
RA Heath P.D., Heathcott R., Holmes S.J., Howden P.J., Howe K.L., Howell G.R.,
RA Huckle E., Humphray S.J., Humphries M.D., Hunt A.R., Johnson C.M.,
RA Joy A.A., Kay M., Keenan S.J., Kimberley A.M., King A., Laird G.K.,
RA Langford C., Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C.R.,
RA Lloyd D.M., Loveland J.E., Lovell J., Martin S., Mashreghi-Mohammadi M.,
RA Maslen G.L., Matthews L., McCann O.T., McLaren S.J., McLay K., McMurray A.,
RA Moore M.J.F., Mullikin J.C., Niblett D., Nickerson T., Novik K.L.,
RA Oliver K., Overton-Larty E.K., Parker A., Patel R., Pearce A.V., Peck A.I.,
RA Phillimore B.J.C.T., Phillips S., Plumb R.W., Porter K.M., Ramsey Y.,
RA Ranby S.A., Rice C.M., Ross M.T., Searle S.M., Sehra H.K., Sheridan E.,
RA Skuce C.D., Smith S., Smith M., Spraggon L., Squares S.L., Steward C.A.,
RA Sycamore N., Tamlyn-Hall G., Tester J., Theaker A.J., Thomas D.W.,
RA Thorpe A., Tracey A., Tromans A., Tubby B., Wall M., Wallis J.M.,
RA West A.P., White S.S., Whitehead S.L., Whittaker H., Wild A., Willey D.J.,
RA Wilmer T.E., Wood J.M., Wray P.W., Wyatt J.C., Young L., Younger R.M.,
RA Bentley D.R., Coulson A., Durbin R.M., Hubbard T., Sulston J.E., Dunham I.,
RA Rogers J., Beck S.;
RT "The DNA sequence and analysis of human chromosome 6.";
RL Nature 425:805-811(2003).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Placenta;
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 [7]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 30-222, AND VARIANT LEU-71.
RX PubMed=9480897; DOI=10.1042/bj3300827;
RA Board P.G.;
RT "Identification of cDNAs encoding two human alpha class glutathione
RT transferases (GSTA3 and GSTA4) and the heterologous expression of GSTA4-
RT 4.";
RL Biochem. J. 330:827-831(1998).
RN [8]
RP X-RAY CRYSTALLOGRAPHY (2.4 ANGSTROMS) IN COMPLEX WITH GLUTATHIONE,
RP BIOPHYSICOCHEMICAL PROPERTIES, AND FUNCTION.
RX PubMed=15595823; DOI=10.1021/bi048757g;
RA Gu Y., Guo J., Pal A., Pan S.S., Zimniak P., Singh S.V., Ji X.;
RT "Crystal structure of human glutathione S-transferase A3-3 and mechanistic
RT implications for its high steroid isomerase activity.";
RL Biochemistry 43:15673-15679(2004).
RN [9]
RP X-RAY CRYSTALLOGRAPHY (1.8 ANGSTROMS) IN COMPLEX WITH GLUTATHIONE AND
RP DELTA5-ANDROSTENE-3-17-DIONE, FUNCTION, AND SUBUNIT.
RX PubMed=20083122; DOI=10.1016/j.jmb.2010.01.023;
RA Tars K., Olin B., Mannervik B.;
RT "Structural basis for featuring of steroid isomerase activity in alpha
RT class glutathione transferases.";
RL J. Mol. Biol. 397:332-340(2010).
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. Has
CC substantial activity toward aflatoxin B1-8,9-epoxide (By similarity).
CC {ECO:0000250|UniProtKB:P30115, ECO:0000269|PubMed:11418619,
CC ECO:0000269|PubMed:15595823, ECO:0000269|PubMed:20083122}.
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:0000305|PubMed:11418619};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:16438;
CC Evidence={ECO:0000305|PubMed:11418619};
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:0000269|PubMed:11418619};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:43937;
CC Evidence={ECO:0000305|PubMed:11418619};
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:0000269|PubMed:11418619};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:43929;
CC Evidence={ECO:0000305|PubMed:11418619};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=23 uM for androst-5-ene-3,17-dione {ECO:0000269|PubMed:15595823};
CC KM=24 uM for androst-5-ene-3,17-dione (at pH 8.0 and 30 degrees
CC Celsius) {ECO:0000269|PubMed:11418619};
CC KM=24 uM for androst-5-ene-3,17-dione (at pH 7.4 and 37 degrees
CC Celsius) {ECO:0000269|PubMed:11418619};
CC KM=17 uM for pregn-5-ene-3,20-dione (at pH 8.0 and 30 degrees
CC Celsius) {ECO:0000269|PubMed:11418619};
CC KM=17 uM for pregn-5-ene-3,20-dione (at pH 7.4 and 37 degrees
CC Celsius) {ECO:0000269|PubMed:11418619};
CC Vmax=99 umol/min/mg enzyme for delta(5)-androstene-3,17-dione
CC isomerization {ECO:0000269|PubMed:15595823};
CC Note=kcats are 102 sec(-1) and 27 sec(-1) for androst-5-ene-3,17-
CC dione and pregn-5-ene-3,20-dione as substrates, respectively (at pH
CC 8.0 and 30 degrees Celsius). {ECO:0000269|PubMed:11418619};
CC -!- SUBUNIT: Homodimer. {ECO:0000269|PubMed:15595823,
CC ECO:0000269|PubMed:20083122}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm.
CC -!- SIMILARITY: Belongs to the GST superfamily. Alpha family.
CC {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAA74634.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
CC Sequence=AAD04712.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
CC -!- WEB RESOURCE: Name=NIEHS-SNPs;
CC URL="http://egp.gs.washington.edu/data/gsta3/";
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DR EMBL; L13275; AAA74634.1; ALT_INIT; Genomic_DNA.
DR EMBL; L13270; AAA74634.1; JOINED; Genomic_DNA.
DR EMBL; L13271; AAA74634.1; JOINED; Genomic_DNA.
DR EMBL; L13272; AAA74634.1; JOINED; Genomic_DNA.
DR EMBL; L13273; AAA74634.1; JOINED; Genomic_DNA.
DR EMBL; L13274; AAA74634.1; JOINED; Genomic_DNA.
DR EMBL; AF508266; AAM33360.1; -; mRNA.
DR EMBL; DQ993361; ABI75350.1; -; Genomic_DNA.
DR EMBL; AL121969; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471081; EAX04391.1; -; Genomic_DNA.
DR EMBL; BC020619; AAH20619.1; -; mRNA.
DR EMBL; AF020919; AAD04712.1; ALT_INIT; mRNA.
DR CCDS; CCDS4947.1; -.
DR PIR; A49365; A49365.
DR RefSeq; NP_000838.3; NM_000847.4.
DR PDB; 1TDI; X-ray; 2.40 A; A/B=1-222.
DR PDB; 2VCV; X-ray; 1.80 A; A/B/C/D/E/F/G/H/I/J/K/L/M/N/O/P=1-222.
DR PDBsum; 1TDI; -.
DR PDBsum; 2VCV; -.
DR AlphaFoldDB; Q16772; -.
DR SMR; Q16772; -.
DR BioGRID; 109195; 4.
DR STRING; 9606.ENSP00000211122; -.
DR ChEMBL; CHEMBL4866; -.
DR DrugBank; DB04521; 4-S-Glutathionyl-5-pentyl-tetrahydro-furan-2-ol.
DR DrugBank; DB00143; Glutathione.
DR SwissLipids; SLP:000001612; -.
DR iPTMnet; Q16772; -.
DR PhosphoSitePlus; Q16772; -.
DR BioMuta; GSTA3; -.
DR DMDM; 21264437; -.
DR jPOST; Q16772; -.
DR MassIVE; Q16772; -.
DR MaxQB; Q16772; -.
DR PaxDb; Q16772; -.
DR PeptideAtlas; Q16772; -.
DR PRIDE; Q16772; -.
DR ProteomicsDB; 61058; -.
DR Antibodypedia; 30950; 316 antibodies from 29 providers.
DR DNASU; 2940; -.
DR Ensembl; ENST00000211122.4; ENSP00000211122.3; ENSG00000174156.15.
DR GeneID; 2940; -.
DR KEGG; hsa:2940; -.
DR MANE-Select; ENST00000211122.4; ENSP00000211122.3; NM_000847.5; NP_000838.3.
DR UCSC; uc003pbb.4; human.
DR CTD; 2940; -.
DR DisGeNET; 2940; -.
DR GeneCards; GSTA3; -.
DR HGNC; HGNC:4628; GSTA3.
DR HPA; ENSG00000174156; Group enriched (adrenal gland, fallopian tube, placenta, skin).
DR MIM; 605449; gene.
DR neXtProt; NX_Q16772; -.
DR OpenTargets; ENSG00000174156; -.
DR PharmGKB; PA29018; -.
DR VEuPathDB; HostDB:ENSG00000174156; -.
DR eggNOG; KOG1695; Eukaryota.
DR GeneTree; ENSGT00940000164319; -.
DR HOGENOM; CLU_039475_4_0_1; -.
DR InParanoid; Q16772; -.
DR OMA; SEMIMLL; -.
DR OrthoDB; 1162336at2759; -.
DR PhylomeDB; Q16772; -.
DR TreeFam; TF105321; -.
DR BRENDA; 2.5.1.18; 2681.
DR BRENDA; 5.3.3.1; 2681.
DR PathwayCommons; Q16772; -.
DR Reactome; R-HSA-156590; Glutathione conjugation.
DR Reactome; R-HSA-9759194; Nuclear events mediated by NFE2L2.
DR SABIO-RK; Q16772; -.
DR SignaLink; Q16772; -.
DR BioGRID-ORCS; 2940; 9 hits in 1004 CRISPR screens.
DR EvolutionaryTrace; Q16772; -.
DR GeneWiki; GSTA3; -.
DR GenomeRNAi; 2940; -.
DR Pharos; Q16772; Tbio.
DR PRO; PR:Q16772; -.
DR Proteomes; UP000005640; Chromosome 6.
DR RNAct; Q16772; protein.
DR Bgee; ENSG00000174156; Expressed in right uterine tube and 102 other tissues.
DR ExpressionAtlas; Q16772; baseline and differential.
DR Genevisible; Q16772; HS.
DR GO; GO:0005829; C:cytosol; IDA:HPA.
DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR GO; GO:0004364; F:glutathione transferase activity; ISS:UniProtKB.
DR GO; GO:0006749; P:glutathione metabolic process; ISS:UniProtKB.
DR GO; GO:0006629; P:lipid metabolic process; IEA:UniProtKB-KW.
DR GO; GO:0006805; P:xenobiotic metabolic process; IBA:GO_Central.
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 Pfam; PF14497; GST_C_3; 1.
DR Pfam; PF02798; GST_N; 1.
DR PRINTS; PR01266; GSTRNSFRASEA.
DR SFLD; SFLDS00019; Glutathione_Transferase_(cytos; 1.
DR SUPFAM; SSF47616; SSF47616; 1.
DR SUPFAM; SSF52833; SSF52833; 1.
DR PROSITE; PS50405; GST_CTER; 1.
DR PROSITE; PS50404; GST_NTER; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Cytoplasm; Lipid metabolism; Reference proteome;
KW Transferase.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000250|UniProtKB:P30115"
FT CHAIN 2..222
FT /note="Glutathione S-transferase A3"
FT /id="PRO_0000185785"
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:0000269|PubMed:15595823,
FT ECO:0000269|PubMed:20083122"
FT BINDING 45
FT /ligand="glutathione"
FT /ligand_id="ChEBI:CHEBI:57925"
FT /evidence="ECO:0000269|PubMed:15595823,
FT ECO:0000269|PubMed:20083122"
FT BINDING 54..55
FT /ligand="glutathione"
FT /ligand_id="ChEBI:CHEBI:57925"
FT /evidence="ECO:0000269|PubMed:15595823,
FT ECO:0000269|PubMed:20083122"
FT BINDING 67..68
FT /ligand="glutathione"
FT /ligand_id="ChEBI:CHEBI:57925"
FT /evidence="ECO:0000269|PubMed:15595823,
FT ECO:0000269|PubMed:20083122"
FT MOD_RES 2
FT /note="N-acetylalanine"
FT /evidence="ECO:0000250|UniProtKB:P30115"
FT MOD_RES 4
FT /note="N6-succinyllysine"
FT /evidence="ECO:0000250|UniProtKB:P30115"
FT VARIANT 36
FT /note="G -> E (in dbSNP:rs45504096)"
FT /evidence="ECO:0000269|Ref.3"
FT /id="VAR_062276"
FT VARIANT 71
FT /note="I -> L (in dbSNP:rs1052661)"
FT /evidence="ECO:0000269|PubMed:9480897, ECO:0000269|Ref.3"
FT /id="VAR_049484"
FT VARIANT 73
FT /note="N -> D (in dbSNP:rs41273858)"
FT /evidence="ECO:0000269|Ref.3"
FT /id="VAR_049485"
FT VARIANT 113
FT /note="R -> Q (in dbSNP:rs45602042)"
FT /evidence="ECO:0000269|Ref.3"
FT /id="VAR_062277"
FT VARIANT 208
FT /note="A -> T (in dbSNP:rs45620832)"
FT /evidence="ECO:0000269|Ref.3"
FT /id="VAR_062278"
FT CONFLICT 63
FT /note="M -> I (in Ref. 6; AAH20619)"
FT /evidence="ECO:0000305"
FT CONFLICT 113..114
FT /note="RP -> PA (in Ref. 1; AAA74634)"
FT /evidence="ECO:0000305"
FT CONFLICT 128
FT /note="T -> I (in Ref. 1; AAA74634)"
FT /evidence="ECO:0000305"
FT STRAND 6..9
FT /evidence="ECO:0007829|PDB:2VCV"
FT TURN 14..16
FT /evidence="ECO:0007829|PDB:2VCV"
FT HELIX 17..25
FT /evidence="ECO:0007829|PDB:2VCV"
FT STRAND 31..34
FT /evidence="ECO:0007829|PDB:2VCV"
FT HELIX 38..46
FT /evidence="ECO:0007829|PDB:2VCV"
FT STRAND 57..60
FT /evidence="ECO:0007829|PDB:2VCV"
FT STRAND 63..67
FT /evidence="ECO:0007829|PDB:2VCV"
FT HELIX 68..78
FT /evidence="ECO:0007829|PDB:2VCV"
FT HELIX 86..108
FT /evidence="ECO:0007829|PDB:2VCV"
FT HELIX 109..111
FT /evidence="ECO:0007829|PDB:2VCV"
FT HELIX 114..130
FT /evidence="ECO:0007829|PDB:2VCV"
FT HELIX 132..143
FT /evidence="ECO:0007829|PDB:2VCV"
FT STRAND 146..149
FT /evidence="ECO:0007829|PDB:2VCV"
FT HELIX 155..170
FT /evidence="ECO:0007829|PDB:2VCV"
FT TURN 172..177
FT /evidence="ECO:0007829|PDB:2VCV"
FT HELIX 179..190
FT /evidence="ECO:0007829|PDB:2VCV"
FT HELIX 192..197
FT /evidence="ECO:0007829|PDB:2VCV"
FT HELIX 210..220
FT /evidence="ECO:0007829|PDB:2VCV"
SQ SEQUENCE 222 AA; 25302 MW; 904AA17519B5343C CRC64;
MAGKPKLHYF NGRGRMEPIR WLLAAAGVEF EEKFIGSAED LGKLRNDGSL MFQQVPMVEI
DGMKLVQTRA ILNYIASKYN LYGKDIKERA LIDMYTEGMA DLNEMILLLP LCRPEEKDAK
IALIKEKTKS RYFPAFEKVL QSHGQDYLVG NKLSRADISL VELLYYVEEL DSSLISNFPL
LKALKTRISN LPTVKKFLQP GSPRKPPADA KALEEARKIF RF
