GSTA1_HUMAN
ID GSTA1_HUMAN Reviewed; 222 AA.
AC P08263; Q14750; Q5GHF8; Q5SZC1;
DT 01-AUG-1988, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 3.
DT 03-AUG-2022, entry version 222.
DE RecName: Full=Glutathione S-transferase A1 {ECO:0000305|PubMed:20606271, ECO:0000305|PubMed:9084911};
DE EC=2.5.1.18 {ECO:0000269|PubMed:20606271};
DE AltName: Full=13-hydroperoxyoctadecadienoate peroxidase {ECO:0000305|PubMed:16624487};
DE EC=1.11.1.- {ECO:0000269|PubMed:16624487};
DE AltName: Full=Androst-5-ene-3,17-dione isomerase {ECO:0000305|PubMed:11152686};
DE EC=5.3.3.- {ECO:0000269|PubMed:11152686};
DE AltName: Full=GST HA subunit 1;
DE AltName: Full=GST class-alpha member 1;
DE AltName: Full=GST-epsilon;
DE AltName: Full=GSTA1-1;
DE AltName: Full=GTH1;
DE Contains:
DE RecName: Full=Glutathione S-transferase A1, N-terminally processed;
GN Name=GSTA1;
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 [MRNA].
RX PubMed=3800996; DOI=10.1016/s0006-291x(86)80358-8;
RA Tu C.-P.D., Qian B.;
RT "Human liver glutathione S-transferases: complete primary sequence of an Ha
RT subunit cDNA.";
RL Biochem. Biophys. Res. Commun. 141:229-237(1986).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=3036131; DOI=10.1016/0006-291x(87)91345-3;
RA Rhoads D.M., Zarlengo R.P., Tu C.-P.D.;
RT "The basic glutathione S-transferases from human livers are products of
RT separate genes.";
RL Biochem. Biophys. Res. Commun. 145:474-481(1987).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Liver;
RX PubMed=3678589; DOI=10.1042/bst0150734;
RA Tu C.-P.D., Qian B.;
RT "Nucleotide sequence of the human liver glutathione S-transferase subunit 1
RT cDNA.";
RL Biochem. Soc. Trans. 15:734-736(1987).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=3031680; DOI=10.1073/pnas.84.8.2377;
RA Board P.G., Webb G.C.;
RT "Isolation of a cDNA clone and localization of human glutathione S-
RT transferase 2 genes to chromosome band 6p12.";
RL Proc. Natl. Acad. Sci. U.S.A. 84:2377-2381(1987).
RN [5]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=1731620; DOI=10.1016/0003-9861(92)90035-u;
RA Rozen F., Nguyen T., Pickett C.B.;
RT "Isolation and characterization of a human glutathione S-transferase Ha1
RT subunit gene.";
RL Arch. Biochem. Biophys. 292:589-593(1992).
RN [6]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=1330133; DOI=10.1016/1046-5928(92)90060-a;
RA Stenberg G., Bjornestedt R., Mannervik B.;
RT "Heterologous expression of recombinant human glutathione transferase A1-1
RT from a hepatoma cell line.";
RL Protein Expr. Purif. 3:80-84(1992).
RN [7]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Liver;
RA Chen P., Zhang C., Xie D., Wu Y., Han L., Chen L.;
RL Submitted (JAN-2004) to the EMBL/GenBank/DDBJ databases.
RN [8]
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 [9]
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 [10]
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 [11]
RP NUCLEOTIDE SEQUENCE OF 1-9.
RX PubMed=3138230; DOI=10.1016/s0021-9258(18)37626-9;
RA Chow N.W., Whang-Peng J., Kao-Shan C.S., Tam M.F., Lai H.-C.J., Tu C.-P.D.;
RT "Human glutathione S-transferases. The Ha multigene family encodes products
RT of different but overlapping substrate specificities.";
RL J. Biol. Chem. 263:12797-12800(1988).
RN [12]
RP PROTEIN SEQUENCE OF 2-170; 188-195 AND 209-222.
RX PubMed=8431482; DOI=10.1016/0167-4838(93)90234-i;
RA Ahmad H., Singhal S.S., Saxena M., Awasthi Y.C.;
RT "Characterization of two novel subunits of the alpha-class glutathione S-
RT transferases of human liver.";
RL Biochim. Biophys. Acta 1161:333-336(1993).
RN [13]
RP PROTEIN SEQUENCE OF 16-36; 63-155 AND 208-212.
RX PubMed=2604726; DOI=10.1042/bj2640437;
RA Hayes J.D., Kerr L.A., Cronshaw A.D.;
RT "Evidence that glutathione S-transferases B1B1 and B2B2 are the products of
RT separate genes and that their expression in human liver is subject to
RT inter-individual variation. Molecular relationships between the B1 and B2
RT subunits and other alpha class glutathione S-transferases.";
RL Biochem. J. 264:437-445(1989).
RN [14]
RP PROTEIN SEQUENCE OF 200-222.
RX PubMed=2018473; DOI=10.1042/bj2750171;
RA Board P.G., Mannervik B.;
RT "The contribution of the C-terminal sequence to the catalytic activity of
RT GST2, a human alpha-class glutathione transferase.";
RL Biochem. J. 275:171-174(1991).
RN [15]
RP FUNCTION, CATALYTIC ACTIVITY, AND BIOPHYSICOCHEMICAL PROPERTIES.
RX PubMed=9084911; DOI=10.1021/tx9601770;
RA Bogaards J.J., Venekamp J.C., van Bladeren P.J.;
RT "Stereoselective conjugation of prostaglandin A2 and prostaglandin J2 with
RT glutathione, catalyzed by the human glutathione S-transferases A1-1, A2-2,
RT M1a-1a, and P1-1.";
RL Chem. Res. Toxicol. 10:310-317(1997).
RN [16]
RP FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, ACTIVITY
RP REGULATION, AND MUTAGENESIS OF TYR-9.
RX PubMed=11152686; DOI=10.1074/jbc.m009146200;
RA Pettersson P.L., Mannervik B.;
RT "The role of glutathione in the isomerization of delta 5-androstene-3,17-
RT dione catalyzed by human glutathione transferase A1-1.";
RL J. Biol. Chem. 276:11698-11704(2001).
RN [17]
RP FUNCTION, AND CATALYTIC ACTIVITY.
RX PubMed=16624487; DOI=10.1016/j.bbagen.2006.02.020;
RA Seeley S.K., Poposki J.A., Maksimchuk J., Tebbe J., Gaudreau J.,
RA Mannervik B., Bull A.W.;
RT "Metabolism of oxidized linoleic acid by glutathione transferases:
RT peroxidase activity toward 13-hydroperoxyoctadecadienoic acid.";
RL Biochim. Biophys. Acta 1760:1064-1070(2006).
RN [18]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [19]
RP X-RAY CRYSTALLOGRAPHY (2.6 ANGSTROMS) IN COMPLEX WITH S-BENZYL-GLUTATHIONE,
RP AND SUBUNIT.
RX PubMed=8331657; DOI=10.1006/jmbi.1993.1376;
RA Sinning I., Kleywegt G.J., Cowan S.W., Reinemer P., Dirr H.W., Huber R.,
RA Gilliland G.L., Armstrong R.N., Ji X., Board P.G., Olin B., Mannervik B.,
RA Jones T.A.;
RT "Structure determination and refinement of human alpha class glutathione
RT transferase A1-1, and a comparison with the Mu and Pi class enzymes.";
RL J. Mol. Biol. 232:192-212(1993).
RN [20]
RP X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS) IN COMPLEXES WITH ETHACRYNIC ACID AND
RP GLUTATHIONE, AND SUBUNIT.
RX PubMed=8591048; DOI=10.1016/s0969-2126(01)00206-4;
RA Cameron A.D., Sinning I., L'Hermite G., Olin B., Board P.G., Mannervik B.,
RA Jones T.A.;
RT "Structural analysis of human alpha-class glutathione transferase A1-1 in
RT the apo-form and in complexes with ethacrynic acid and its glutathione
RT conjugate.";
RL Structure 3:717-727(1995).
RN [21]
RP X-RAY CRYSTALLOGRAPHY (1.3 ANGSTROMS) IN COMPLEXES WITH S-HEXYL
RP GLUTATHIONE, AND SUBUNIT.
RX PubMed=12211029; DOI=10.1002/prot.10162;
RA Le Trong I., Stenkamp R.E., Ibarra C., Atkins W.M., Adman E.T.;
RT "1.3-A resolution structure of human glutathione S-transferase with S-hexyl
RT glutathione bound reveals possible extended ligandin binding site.";
RL Proteins 48:618-627(2002).
RN [22]
RP X-RAY CRYSTALLOGRAPHY (2.07 ANGSTROMS) IN COMPLEX WITH S-BENZYLGLUTATHIONE,
RP AND MUTAGENESIS OF ALA-216.
RX PubMed=15333749; DOI=10.1073/pnas.0403045101;
RA Hederos S., Broo K.S., Jakobsson E., Kleywegt G.J., Mannervik B.,
RA Baltzer L.;
RT "Incorporation of a single His residue by rational design enables thiol-
RT ester hydrolysis by human glutathione transferase A1-1.";
RL Proc. Natl. Acad. Sci. U.S.A. 101:13163-13167(2004).
RN [23]
RP X-RAY CRYSTALLOGRAPHY (1.95 ANGSTROMS) OF MUTANT ALA-219 IN COMPLEX WITH
RP S-HEXYLGLUTATHIONE.
RX PubMed=15893769; DOI=10.1016/j.jmb.2005.04.025;
RA Kuhnert D.C., Sayed Y., Mosebi S., Sayed M., Sewell T., Dirr H.W.;
RT "Tertiary interactions stabilise the C-terminal region of human glutathione
RT transferase A1-1: a crystallographic and calorimetric study.";
RL J. Mol. Biol. 349:825-838(2005).
RN [24]
RP X-RAY CRYSTALLOGRAPHY (1.75 ANGSTROMS) IN COMPLEX WITH GLUTATHIONE, AND
RP SUBUNIT.
RX PubMed=16421451; DOI=10.1107/s0907444905039296;
RA Grahn E., Novotny M., Jakobsson E., Gustafsson A., Grehn L., Olin B.,
RA Madsen D., Wahlberg M., Mannervik B., Kleywegt G.J.;
RT "New crystal structures of human glutathione transferase A1-1 shed light on
RT glutathione binding and the conformation of the C-terminal helix.";
RL Acta Crystallogr. D 62:197-207(2006).
RN [25]
RP X-RAY CRYSTALLOGRAPHY (1.98 ANGSTROMS) OF 1-210 IN COMPLEX WITH
RP GLUTATHIONE.
RX PubMed=19618965; DOI=10.1021/bi900895b;
RA Balogh L.M., Le Trong I., Kripps K.A., Tars K., Stenkamp R.E.,
RA Mannervik B., Atkins W.M.;
RT "Structural analysis of a glutathione transferase A1-1 mutant tailored for
RT high catalytic efficiency with toxic alkenals.";
RL Biochemistry 48:7698-7704(2009).
RN [26]
RP X-RAY CRYSTALLOGRAPHY (1.75 ANGSTROMS) OF MUTANTS ALA-71 AND VAL-71 IN
RP COMPLEX WITH S-HEXYLGLUTATHIONE, FUNCTION, CATALYTIC ACTIVITY, AND
RP MUTAGENESIS OF ILE-71.
RX PubMed=20606271; DOI=10.1107/s1744309110019135;
RA Achilonu I., Gildenhuys S., Fisher L., Burke J., Fanucchi S., Sewell B.T.,
RA Fernandes M., Dirr H.W.;
RT "The role of a topologically conserved isoleucine in glutathione
RT transferase structure, stability and function.";
RL Acta Crystallogr. F 66:776-780(2010).
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 (Probable). Involved
CC in the formation of glutathione conjugates of both prostaglandin A2
CC (PGA2) and prostaglandin J2 (PGJ2) (PubMed:9084911). 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 (PubMed:11152686). Through its glutathione-dependent
CC peroxidase activity toward the fatty acid hydroperoxide (13S)-
CC hydroperoxy-(9Z,11E)-octadecadienoate/13-HPODE it is also involved in
CC the metabolism of oxidized linoleic acid (PubMed:16624487).
CC {ECO:0000269|PubMed:11152686, ECO:0000269|PubMed:16624487,
CC ECO:0000269|PubMed:9084911, ECO:0000305|PubMed:20606271}.
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:0000269|PubMed:20606271};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:16438;
CC Evidence={ECO:0000305|PubMed:20606271};
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:0000269|PubMed:9084911};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:50797;
CC Evidence={ECO:0000305|PubMed:9084911};
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:0000269|PubMed:9084911};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:50805;
CC Evidence={ECO:0000305|PubMed:9084911};
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:0000269|PubMed:16624487};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:48889;
CC Evidence={ECO:0000305|PubMed:16624487};
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:11152686};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:43937;
CC Evidence={ECO:0000305|PubMed:11152686};
CC -!- ACTIVITY REGULATION: The isomerase activity is inhibited by S-
CC methylglutathione (GSMe). {ECO:0000269|PubMed:11152686}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=160 uM for prostaglandin A2 (at pH 7.0 and 37 degrees Celsius)
CC {ECO:0000269|PubMed:9084911};
CC KM=160 uM for glutathione (at pH 8.0) {ECO:0000269|PubMed:11152686};
CC KM=58 uM for androst-5-ene-3,17-dione (at pH 8.0)
CC {ECO:0000269|PubMed:11152686};
CC Vmax=121 nmol/min/mg enzyme for the formation of the glutathione-S-
CC conjugate of prostaglandin A2 (at pH 7.0 and 37 degrees Celsius)
CC {ECO:0000269|PubMed:9084911};
CC Vmax=40 umol/min/mg enzyme for the isomerization of androst-5-ene-
CC 3,17-dione (at pH 8.0) {ECO:0000269|PubMed:11152686};
CC Note=kcat is 29.3 sec(-1) for the isomerization of androst-5-ene-
CC 3,17-dione. {ECO:0000269|PubMed:11152686};
CC pH dependence:
CC Optimum pH is 8.0 for the isomerization of androst-5-ene-3,17-dione.
CC {ECO:0000269|PubMed:11152686};
CC -!- SUBUNIT: Homodimer or heterodimer of GSTA1 and GSTA2.
CC {ECO:0000269|PubMed:12211029, ECO:0000269|PubMed:15333749,
CC ECO:0000269|PubMed:15893769, ECO:0000269|PubMed:16421451,
CC ECO:0000269|PubMed:19618965, ECO:0000269|PubMed:20606271,
CC ECO:0000269|PubMed:8331657, ECO:0000269|PubMed:8591048}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm.
CC -!- TISSUE SPECIFICITY: Liver.
CC -!- DOMAIN: The C-terminal domain may form a component of the hydrophobic
CC substrate-binding site, but in contrast appears not to be directly
CC involved in GSH binding and is not absolutely essential for catalytic
CC activity.
CC -!- SIMILARITY: Belongs to the GST superfamily. Alpha family.
CC {ECO:0000305}.
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DR EMBL; M15872; AAA70226.1; -; mRNA.
DR EMBL; M21758; AAA52615.1; -; mRNA.
DR EMBL; M25627; AAA36174.1; -; mRNA.
DR EMBL; M14777; AAA52618.1; -; mRNA.
DR EMBL; S76235; AAB20973.1; -; Genomic_DNA.
DR EMBL; S76221; AAB20973.1; JOINED; Genomic_DNA.
DR EMBL; S76223; AAB20973.1; JOINED; Genomic_DNA.
DR EMBL; S76225; AAB20973.1; JOINED; Genomic_DNA.
DR EMBL; S76228; AAB20973.1; JOINED; Genomic_DNA.
DR EMBL; S76232; AAB20973.1; JOINED; Genomic_DNA.
DR EMBL; S49975; AAB24012.1; -; mRNA.
DR EMBL; AY532928; AAT06769.1; -; mRNA.
DR EMBL; CR407656; CAG28584.1; -; mRNA.
DR EMBL; AL590363; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471081; EAX04385.1; -; Genomic_DNA.
DR EMBL; BC053578; AAH53578.1; -; mRNA.
DR EMBL; BC110891; AAI10892.1; -; mRNA.
DR CCDS; CCDS4945.1; -.
DR PIR; A25909; A56666.
DR PIR; S29657; S29657.
DR RefSeq; NP_665683.1; NM_145740.4.
DR PDB; 1GSD; X-ray; 2.50 A; A/B/C/D=2-222.
DR PDB; 1GSE; X-ray; 2.00 A; A/B=2-222.
DR PDB; 1GSF; X-ray; 2.70 A; A/B/C/D=2-222.
DR PDB; 1GUH; X-ray; 2.60 A; A/B/C/D=2-222.
DR PDB; 1K3L; X-ray; 1.50 A; A/B=2-222.
DR PDB; 1K3O; X-ray; 1.80 A; A/B=2-222.
DR PDB; 1K3Y; X-ray; 1.30 A; A/B=2-222.
DR PDB; 1LBK; X-ray; 1.86 A; A/B=208-213.
DR PDB; 1PKW; X-ray; 2.00 A; A/B=1-222.
DR PDB; 1PKZ; X-ray; 2.10 A; A/B=1-222.
DR PDB; 1PL1; X-ray; 1.75 A; A/B=1-222.
DR PDB; 1PL2; X-ray; 1.80 A; A/B=1-222.
DR PDB; 1USB; X-ray; 2.07 A; A/B=2-222.
DR PDB; 1XWG; X-ray; 1.85 A; A/B=2-222.
DR PDB; 1YDK; X-ray; 1.95 A; A/B=1-222.
DR PDB; 2R3X; X-ray; 1.80 A; A/B=1-222.
DR PDB; 2R6K; X-ray; 2.51 A; A/B=1-222.
DR PDB; 3I69; X-ray; 2.38 A; A/B/C/D/E/F/G/H=1-222.
DR PDB; 3I6A; X-ray; 1.98 A; A/B/C/D/E/F/G/H=1-222.
DR PDB; 3IK9; X-ray; 2.20 A; A/B/C/D/E/F/G/H=1-222.
DR PDB; 3KTL; X-ray; 1.75 A; A/B=2-222.
DR PDB; 3L0H; X-ray; 2.13 A; A/B=1-222.
DR PDB; 3Q74; X-ray; 1.79 A; A/B=2-222.
DR PDB; 3U6V; X-ray; 2.20 A; A/B=1-222.
DR PDB; 3ZFB; X-ray; 1.86 A; A/B=1-222.
DR PDB; 3ZFL; X-ray; 1.88 A; A/B=1-222.
DR PDB; 4HJ2; X-ray; 2.10 A; A/B=4-220.
DR PDB; 5JCU; X-ray; 1.93 A; A/B/C/D=2-222.
DR PDB; 5LCZ; X-ray; 2.33 A; A/B=1-100, A/B=201-222.
DR PDB; 5LD0; X-ray; 1.60 A; A=1-85, A=214-222.
DR PDB; 6ATO; X-ray; 1.55 A; A/B=2-222.
DR PDB; 6ATP; X-ray; 1.70 A; A/B=2-222.
DR PDB; 6ATQ; X-ray; 2.00 A; A/B=2-222.
DR PDB; 6ATR; X-ray; 1.29 A; A/B=2-222.
DR PDB; 6YAW; X-ray; 2.19 A; A/B=1-222.
DR PDB; 7BIB; X-ray; 2.03 A; A/B=1-222.
DR PDB; 7BIC; X-ray; 2.46 A; A/B/C/D=1-222.
DR PDBsum; 1GSD; -.
DR PDBsum; 1GSE; -.
DR PDBsum; 1GSF; -.
DR PDBsum; 1GUH; -.
DR PDBsum; 1K3L; -.
DR PDBsum; 1K3O; -.
DR PDBsum; 1K3Y; -.
DR PDBsum; 1LBK; -.
DR PDBsum; 1PKW; -.
DR PDBsum; 1PKZ; -.
DR PDBsum; 1PL1; -.
DR PDBsum; 1PL2; -.
DR PDBsum; 1USB; -.
DR PDBsum; 1XWG; -.
DR PDBsum; 1YDK; -.
DR PDBsum; 2R3X; -.
DR PDBsum; 2R6K; -.
DR PDBsum; 3I69; -.
DR PDBsum; 3I6A; -.
DR PDBsum; 3IK9; -.
DR PDBsum; 3KTL; -.
DR PDBsum; 3L0H; -.
DR PDBsum; 3Q74; -.
DR PDBsum; 3U6V; -.
DR PDBsum; 3ZFB; -.
DR PDBsum; 3ZFL; -.
DR PDBsum; 4HJ2; -.
DR PDBsum; 5JCU; -.
DR PDBsum; 5LCZ; -.
DR PDBsum; 5LD0; -.
DR PDBsum; 6ATO; -.
DR PDBsum; 6ATP; -.
DR PDBsum; 6ATQ; -.
DR PDBsum; 6ATR; -.
DR PDBsum; 6YAW; -.
DR PDBsum; 7BIB; -.
DR PDBsum; 7BIC; -.
DR AlphaFoldDB; P08263; -.
DR SMR; P08263; -.
DR BioGRID; 109193; 22.
DR IntAct; P08263; 12.
DR STRING; 9606.ENSP00000335620; -.
DR BindingDB; P08263; -.
DR ChEMBL; CHEMBL3409; -.
DR DrugBank; DB02486; 2-Hydroxyethyl Disulfide.
DR DrugBank; DB00993; Azathioprine.
DR DrugBank; DB01008; Busulfan.
DR DrugBank; DB11672; Curcumin.
DR DrugBank; DB00143; Glutathione.
DR DrugBank; DB03310; Glutathione disulfide.
DR DrugBank; DB03003; Glutathione sulfonic acid.
DR DrugBank; DB13014; Hypericin.
DR DrugBank; DB02943; N-(4-Aminobutanoyl)-S-(4-methoxybenzyl)-L-cysteinylglycine.
DR DrugBank; DB03602; S-benzylglutathione.
DR DrugBank; DB04132; S-Hexylglutathione.
DR DrugBank; DB01915; S-Hydroxycysteine.
DR DrugCentral; P08263; -.
DR SwissLipids; SLP:000001476; -.
DR iPTMnet; P08263; -.
DR PhosphoSitePlus; P08263; -.
DR BioMuta; GSTA1; -.
DR DMDM; 121730; -.
DR REPRODUCTION-2DPAGE; IPI00657682; -.
DR jPOST; P08263; -.
DR MassIVE; P08263; -.
DR MaxQB; P08263; -.
DR PaxDb; P08263; -.
DR PeptideAtlas; P08263; -.
DR PRIDE; P08263; -.
DR ProteomicsDB; 52103; -.
DR Antibodypedia; 30937; 517 antibodies from 34 providers.
DR DNASU; 2938; -.
DR Ensembl; ENST00000334575.6; ENSP00000335620.5; ENSG00000243955.6.
DR GeneID; 2938; -.
DR KEGG; hsa:2938; -.
DR MANE-Select; ENST00000334575.6; ENSP00000335620.5; NM_145740.5; NP_665683.1.
DR UCSC; uc003paz.4; human.
DR CTD; 2938; -.
DR DisGeNET; 2938; -.
DR GeneCards; GSTA1; -.
DR HGNC; HGNC:4626; GSTA1.
DR HPA; ENSG00000243955; Tissue enhanced (adrenal gland, kidney, liver).
DR MIM; 138359; gene.
DR neXtProt; NX_P08263; -.
DR OpenTargets; ENSG00000243955; -.
DR PharmGKB; PA29016; -.
DR VEuPathDB; HostDB:ENSG00000243955; -.
DR eggNOG; KOG1695; Eukaryota.
DR GeneTree; ENSGT00940000164034; -.
DR HOGENOM; CLU_039475_4_0_1; -.
DR InParanoid; P08263; -.
DR OMA; CKPDILA; -.
DR PhylomeDB; P08263; -.
DR TreeFam; TF105321; -.
DR BioCyc; MetaCyc:G66-32542-MON; -.
DR BRENDA; 2.5.1.18; 2681.
DR PathwayCommons; P08263; -.
DR Reactome; R-HSA-156590; Glutathione conjugation.
DR Reactome; R-HSA-189483; Heme degradation.
DR Reactome; R-HSA-9748787; Azathioprine ADME.
DR Reactome; R-HSA-9759194; Nuclear events mediated by NFE2L2.
DR SABIO-RK; P08263; -.
DR SignaLink; P08263; -.
DR SIGNOR; P08263; -.
DR BioGRID-ORCS; 2938; 9 hits in 995 CRISPR screens.
DR ChiTaRS; GSTA1; human.
DR EvolutionaryTrace; P08263; -.
DR GeneWiki; Glutathione_S-transferase_A1; -.
DR GenomeRNAi; 2938; -.
DR Pharos; P08263; Tchem.
DR PRO; PR:P08263; -.
DR Proteomes; UP000005640; Chromosome 6.
DR RNAct; P08263; protein.
DR Bgee; ENSG00000243955; Expressed in bronchial epithelial cell and 135 other tissues.
DR ExpressionAtlas; P08263; baseline and differential.
DR Genevisible; P08263; HS.
DR GO; GO:0005829; C:cytosol; IDA:HPA.
DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR GO; GO:0005504; F:fatty acid binding; IPI:BHF-UCL.
DR GO; GO:0004602; F:glutathione peroxidase activity; IDA:BHF-UCL.
DR GO; GO:0004364; F:glutathione transferase activity; IDA:UniProtKB.
DR GO; GO:0004769; F:steroid delta-isomerase activity; IDA:UniProtKB.
DR GO; GO:0030855; P:epithelial cell differentiation; IEP:UniProtKB.
DR GO; GO:1901687; P:glutathione derivative biosynthetic process; IDA:UniProtKB.
DR GO; GO:0006749; P:glutathione metabolic process; IDA:UniProtKB.
DR GO; GO:0043651; P:linoleic acid metabolic process; IDA:BHF-UCL.
DR GO; GO:0006693; P:prostaglandin metabolic process; IDA:UniProtKB.
DR GO; GO:0006805; P:xenobiotic metabolic process; IBA:GO_Central.
DR DisProt; DP01506; -.
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; PF00043; GST_C; 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; Direct protein sequencing; Isomerase;
KW Lipid metabolism; Oxidoreductase; Peroxidase; Reference proteome;
KW Transferase.
FT CHAIN 1..222
FT /note="Glutathione S-transferase A1"
FT /id="PRO_0000423203"
FT INIT_MET 1
FT /note="Removed; alternate"
FT /evidence="ECO:0000250|UniProtKB:P30115,
FT ECO:0000269|PubMed:8431482"
FT CHAIN 2..222
FT /note="Glutathione S-transferase A1, N-terminally
FT processed"
FT /id="PRO_0000185783"
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:16421451,
FT ECO:0000269|PubMed:19618965"
FT BINDING 45
FT /ligand="glutathione"
FT /ligand_id="ChEBI:CHEBI:57925"
FT /evidence="ECO:0000269|PubMed:16421451,
FT ECO:0000269|PubMed:19618965"
FT BINDING 54..55
FT /ligand="glutathione"
FT /ligand_id="ChEBI:CHEBI:57925"
FT /evidence="ECO:0000269|PubMed:16421451,
FT ECO:0000269|PubMed:19618965"
FT BINDING 67..68
FT /ligand="glutathione"
FT /ligand_id="ChEBI:CHEBI:57925"
FT /evidence="ECO:0000269|PubMed:16421451,
FT ECO:0000269|PubMed:19618965"
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 VARIANT 19
FT /note="T -> I (in dbSNP:rs1051578)"
FT /id="VAR_033978"
FT VARIANT 113
FT /note="P -> Q (in dbSNP:rs1051745)"
FT /id="VAR_049482"
FT VARIANT 117
FT /note="K -> Q (in dbSNP:rs1051757)"
FT /id="VAR_049483"
FT MUTAGEN 9
FT /note="Y->F: Decreased isomerase activity."
FT /evidence="ECO:0000269|PubMed:11152686"
FT MUTAGEN 71
FT /note="I->A,V: No significant effect on enzyme activity.
FT Reduces protein stability."
FT /evidence="ECO:0000269|PubMed:20606271"
FT MUTAGEN 216
FT /note="A->H: Confers ability to hydrolyze S-glutathionyl
FT benzoate to glutathione and benzoic acid."
FT /evidence="ECO:0000269|PubMed:15333749"
FT CONFLICT 18
FT /note="S -> C (in Ref. 3; AAA36174)"
FT /evidence="ECO:0000305"
FT CONFLICT 51
FT /note="M -> T (in Ref. 7; AAT06769)"
FT /evidence="ECO:0000305"
FT CONFLICT 56..58
FT /note="PMV -> AML (in Ref. 3; AAA36174)"
FT /evidence="ECO:0000305"
FT CONFLICT 212
FT /note="S -> L (in Ref. 13; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 216
FT /note="A -> S (in Ref. 12; AA sequence)"
FT /evidence="ECO:0000305"
FT STRAND 6..13
FT /evidence="ECO:0007829|PDB:6ATR"
FT TURN 14..16
FT /evidence="ECO:0007829|PDB:6ATR"
FT HELIX 17..25
FT /evidence="ECO:0007829|PDB:6ATR"
FT STRAND 31..35
FT /evidence="ECO:0007829|PDB:6ATR"
FT HELIX 38..46
FT /evidence="ECO:0007829|PDB:6ATR"
FT STRAND 57..60
FT /evidence="ECO:0007829|PDB:6ATR"
FT STRAND 63..67
FT /evidence="ECO:0007829|PDB:6ATR"
FT HELIX 68..78
FT /evidence="ECO:0007829|PDB:6ATR"
FT HELIX 86..108
FT /evidence="ECO:0007829|PDB:6ATR"
FT HELIX 109..111
FT /evidence="ECO:0007829|PDB:6ATR"
FT HELIX 114..130
FT /evidence="ECO:0007829|PDB:6ATR"
FT HELIX 132..143
FT /evidence="ECO:0007829|PDB:6ATR"
FT STRAND 146..149
FT /evidence="ECO:0007829|PDB:6ATR"
FT HELIX 155..170
FT /evidence="ECO:0007829|PDB:6ATR"
FT TURN 172..177
FT /evidence="ECO:0007829|PDB:6ATR"
FT HELIX 179..190
FT /evidence="ECO:0007829|PDB:6ATR"
FT HELIX 192..198
FT /evidence="ECO:0007829|PDB:6ATR"
FT HELIX 210..220
FT /evidence="ECO:0007829|PDB:6ATR"
SQ SEQUENCE 222 AA; 25631 MW; C8B6786DCD761350 CRC64;
MAEKPKLHYF NARGRMESTR WLLAAAGVEF EEKFIKSAED LDKLRNDGYL MFQQVPMVEI
DGMKLVQTRA ILNYIASKYN LYGKDIKERA LIDMYIEGIA DLGEMILLLP VCPPEEKDAK
LALIKEKIKN RYFPAFEKVL KSHGQDYLVG NKLSRADIHL VELLYYVEEL DSSLISSFPL
LKALKTRISN LPTVKKFLQP GSPRKPPMDE KSLEEARKIF RF
