GSTA2_HUMAN
ID GSTA2_HUMAN Reviewed; 222 AA.
AC P09210; Q12759; Q16491; Q9NTY6;
DT 01-JUL-1989, integrated into UniProtKB/Swiss-Prot.
DT 20-FEB-2007, sequence version 4.
DT 03-AUG-2022, entry version 218.
DE RecName: Full=Glutathione S-transferase A2;
DE EC=2.5.1.18 {ECO:0000250|UniProtKB:P10648};
DE AltName: Full=GST HA subunit 2;
DE AltName: Full=GST class-alpha member 2;
DE AltName: Full=GST-gamma;
DE AltName: Full=GSTA2-2;
DE AltName: Full=GTH2;
GN Name=GSTA2; Synonyms=GST2;
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], VARIANT THR-112, AND TISSUE SPECIFICITY.
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 [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANT ALA-210.
RC TISSUE=Liver;
RX PubMed=1329668; DOI=10.1016/0003-9861(92)90475-c;
RA Rohrdanz E., Nguyen T., Pickett C.B.;
RT "Isolation and characterization of the human glutathione S-transferase A2
RT subunit gene.";
RL Arch. Biochem. Biophys. 298:747-752(1992).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANT ALA-210.
RC TISSUE=Blood;
RX PubMed=1497629; DOI=10.1042/bj2850925;
RA Klone A., Hussnatter R., Sies H.;
RT "Cloning, sequencing and characterization of the human alpha glutathione S-
RT transferase gene corresponding to the cDNA clone pGTH2.";
RL Biochem. J. 285:925-928(1992).
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 MRNA], AND VARIANT THR-112.
RC TISSUE=Lung;
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 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 [7]
RP PROTEIN SEQUENCE OF 63-155 AND 208-222.
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 [8]
RP X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS), AND SUBUNIT.
RX PubMed=7892174; DOI=10.1002/prot.340200306;
RA Zeng K., Rose J.P., Chen H.C., Strickland C.L., Tu C.P., Wang B.C.;
RT "A surface mutant (G82R) of a human alpha-glutathione S-transferase shows
RT decreased thermal stability and a new mode of molecular association in the
RT crystal.";
RL Proteins 20:259-263(1994).
RN [9]
RP X-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS) IN COMPLEX WITH GLUTATHIONE AND
RP DELTA5-ANDROSTENE-3-17-DIONE, 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).
RN [10]
RP VARIANTS THR-112 AND ALA-210.
RX PubMed=11668220; DOI=10.1097/00008571-200110000-00007;
RA Tetlow N., Liu D., Board P.;
RT "Polymorphism of human alpha class glutathione transferases.";
RL Pharmacogenetics 11:609-617(2001).
RN [11]
RP VARIANT [LARGE SCALE ANALYSIS] THR-112, AND IDENTIFICATION BY MASS
RP 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).
CC -!- FUNCTION: Catalyzes the conjugation of glutathione to a large variety
CC of electrophilic compounds. {ECO:0000250|UniProtKB:P10648}.
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:P10648};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:16438;
CC Evidence={ECO:0000250|UniProtKB:P10648};
CC -!- SUBUNIT: Homodimer or heterodimer of GSTA1 and GSTA2.
CC {ECO:0000269|PubMed:20083122, ECO:0000269|PubMed:7892174}.
CC -!- INTERACTION:
CC P09210; O15217: GSTA4; NbExp=11; IntAct=EBI-10196201, EBI-752440;
CC P09210; Q7RTV2: GSTA5; NbExp=4; IntAct=EBI-10196201, EBI-13328621;
CC -!- SUBCELLULAR LOCATION: Cytoplasm.
CC -!- TISSUE SPECIFICITY: Liver. {ECO:0000269|PubMed:3036131}.
CC -!- SIMILARITY: Belongs to the GST superfamily. Alpha family.
CC {ECO:0000305}.
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DR EMBL; M16594; AAA52616.1; -; mRNA.
DR EMBL; S45640; AAB23672.1; -; Genomic_DNA.
DR EMBL; S45627; AAB23672.1; JOINED; Genomic_DNA.
DR EMBL; S45629; AAB23672.1; JOINED; Genomic_DNA.
DR EMBL; S45636; AAB23672.1; JOINED; Genomic_DNA.
DR EMBL; S45637; AAB23672.1; JOINED; Genomic_DNA.
DR EMBL; S45639; AAB23672.1; JOINED; Genomic_DNA.
DR EMBL; X65727; CAA46642.1; -; Genomic_DNA.
DR EMBL; X65728; CAA46642.1; JOINED; Genomic_DNA.
DR EMBL; X65729; CAA46642.1; JOINED; Genomic_DNA.
DR EMBL; X65730; CAA46642.1; JOINED; Genomic_DNA.
DR EMBL; X65731; CAA46642.1; JOINED; Genomic_DNA.
DR EMBL; X65732; CAA46642.1; JOINED; Genomic_DNA.
DR EMBL; AL109918; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC002895; AAH02895.1; -; mRNA.
DR CCDS; CCDS4944.1; -.
DR PIR; S24330; S24330.
DR PIR; S29658; S29658.
DR RefSeq; NP_000837.3; NM_000846.4.
DR RefSeq; XP_011512834.1; XM_011514532.2.
DR PDB; 1AGS; X-ray; 2.50 A; A/B=2-222.
DR PDB; 2VCT; X-ray; 2.10 A; A/B/C/D/E/F/G/H=1-222.
DR PDB; 2WJU; X-ray; 2.30 A; A/B/C/D/E/F/G/H=1-222.
DR PDB; 4ACS; X-ray; 2.10 A; A/B/C/D=1-221.
DR PDBsum; 1AGS; -.
DR PDBsum; 2VCT; -.
DR PDBsum; 2WJU; -.
DR PDBsum; 4ACS; -.
DR AlphaFoldDB; P09210; -.
DR SMR; P09210; -.
DR BioGRID; 109194; 9.
DR IntAct; P09210; 5.
DR STRING; 9606.ENSP00000420168; -.
DR BindingDB; P09210; -.
DR ChEMBL; CHEMBL2241; -.
DR DrugBank; DB14001; alpha-Tocopherol succinate.
DR DrugBank; DB00993; Azathioprine.
DR DrugBank; DB01008; Busulfan.
DR DrugBank; DB00608; Chloroquine.
DR DrugBank; DB00636; Clofibrate.
DR DrugBank; DB14002; D-alpha-Tocopherol acetate.
DR DrugBank; DB00903; Etacrynic acid.
DR DrugBank; DB00143; Glutathione.
DR DrugBank; DB03310; Glutathione disulfide.
DR DrugBank; DB00163; Vitamin E.
DR GlyGen; P09210; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; P09210; -.
DR PhosphoSitePlus; P09210; -.
DR BioMuta; GSTA2; -.
DR DMDM; 126302551; -.
DR REPRODUCTION-2DPAGE; IPI00745233; -.
DR jPOST; P09210; -.
DR MassIVE; P09210; -.
DR MaxQB; P09210; -.
DR PaxDb; P09210; -.
DR PeptideAtlas; P09210; -.
DR PRIDE; P09210; -.
DR ProteomicsDB; 52206; -.
DR Antibodypedia; 30929; 230 antibodies from 28 providers.
DR DNASU; 2939; -.
DR Ensembl; ENST00000493422.3; ENSP00000420168.1; ENSG00000244067.3.
DR GeneID; 2939; -.
DR KEGG; hsa:2939; -.
DR MANE-Select; ENST00000493422.3; ENSP00000420168.1; NM_000846.5; NP_000837.3.
DR UCSC; uc003pay.4; human.
DR CTD; 2939; -.
DR DisGeNET; 2939; -.
DR GeneCards; GSTA2; -.
DR HGNC; HGNC:4627; GSTA2.
DR HPA; ENSG00000244067; Group enriched (kidney, liver).
DR MIM; 138360; gene.
DR neXtProt; NX_P09210; -.
DR OpenTargets; ENSG00000244067; -.
DR PharmGKB; PA29017; -.
DR VEuPathDB; HostDB:ENSG00000244067; -.
DR eggNOG; KOG1695; Eukaryota.
DR GeneTree; ENSGT00940000164034; -.
DR HOGENOM; CLU_039475_4_0_1; -.
DR InParanoid; P09210; -.
DR OMA; KERAXID; -.
DR OrthoDB; 1162336at2759; -.
DR PhylomeDB; P09210; -.
DR TreeFam; TF105321; -.
DR BioCyc; MetaCyc:HS01846-MON; -.
DR BRENDA; 2.5.1.18; 2681.
DR PathwayCommons; P09210; -.
DR Reactome; R-HSA-156590; Glutathione conjugation.
DR Reactome; R-HSA-8950505; Gene and protein expression by JAK-STAT signaling after Interleukin-12 stimulation.
DR Reactome; R-HSA-9748787; Azathioprine ADME.
DR SABIO-RK; P09210; -.
DR SignaLink; P09210; -.
DR BioGRID-ORCS; 2939; 19 hits in 983 CRISPR screens.
DR ChiTaRS; GSTA2; human.
DR EvolutionaryTrace; P09210; -.
DR GeneWiki; GSTA2; -.
DR GenomeRNAi; 2939; -.
DR Pharos; P09210; Tbio.
DR PRO; PR:P09210; -.
DR Proteomes; UP000005640; Chromosome 6.
DR RNAct; P09210; protein.
DR Bgee; ENSG00000244067; Expressed in body of pancreas and 68 other tissues.
DR ExpressionAtlas; P09210; baseline and differential.
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:0030855; P:epithelial cell differentiation; IEP:UniProtKB.
DR GO; GO:0006749; P:glutathione metabolic process; ISS:UniProtKB.
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; Direct protein sequencing;
KW Reference proteome; Transferase.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000250|UniProtKB:P30115,
FT ECO:0000269|PubMed:8431482"
FT CHAIN 2..222
FT /note="Glutathione S-transferase A2"
FT /id="PRO_0000185784"
FT DOMAIN 3..83
FT /note="GST N-terminal"
FT DOMAIN 85..207
FT /note="GST C-terminal"
FT REGION 199..222
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 207..222
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 9
FT /ligand="glutathione"
FT /ligand_id="ChEBI:CHEBI:57925"
FT /evidence="ECO:0000269|PubMed:20083122"
FT BINDING 45
FT /ligand="glutathione"
FT /ligand_id="ChEBI:CHEBI:57925"
FT /evidence="ECO:0000269|PubMed:20083122"
FT BINDING 54..55
FT /ligand="glutathione"
FT /ligand_id="ChEBI:CHEBI:57925"
FT /evidence="ECO:0000269|PubMed:20083122"
FT BINDING 67..68
FT /ligand="glutathione"
FT /ligand_id="ChEBI:CHEBI:57925"
FT /evidence="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 110
FT /note="P -> S (in dbSNP:rs2234951)"
FT /id="VAR_014495"
FT VARIANT 112
FT /note="S -> T (in dbSNP:rs2180314)"
FT /evidence="ECO:0000269|PubMed:11668220,
FT ECO:0000269|PubMed:15489334, ECO:0000269|PubMed:3036131,
FT ECO:0007744|PubMed:24275569"
FT /id="VAR_012205"
FT VARIANT 149
FT /note="V -> A (in dbSNP:rs2266631)"
FT /id="VAR_014496"
FT VARIANT 210
FT /note="E -> A (in dbSNP:rs6577)"
FT /evidence="ECO:0000269|PubMed:11668220,
FT ECO:0000269|PubMed:1329668, ECO:0000269|PubMed:1497629"
FT /id="VAR_012206"
FT CONFLICT 10..12
FT /note="SNI -> FNA (in Ref. 6; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 12
FT /note="I -> T (in Ref. 3; CAA46642)"
FT /evidence="ECO:0000305"
FT CONFLICT 19
FT /note="I -> T (in Ref. 6; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 89
FT /note="K -> R (in Ref. 6; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 128
FT /note="T -> I (in Ref. 6; AA sequence)"
FT /evidence="ECO:0000305"
FT STRAND 6..9
FT /evidence="ECO:0007829|PDB:2VCT"
FT STRAND 11..13
FT /evidence="ECO:0007829|PDB:4ACS"
FT TURN 14..16
FT /evidence="ECO:0007829|PDB:2VCT"
FT HELIX 17..25
FT /evidence="ECO:0007829|PDB:2VCT"
FT STRAND 31..34
FT /evidence="ECO:0007829|PDB:2VCT"
FT HELIX 38..46
FT /evidence="ECO:0007829|PDB:2VCT"
FT STRAND 57..60
FT /evidence="ECO:0007829|PDB:2VCT"
FT STRAND 63..67
FT /evidence="ECO:0007829|PDB:2VCT"
FT HELIX 68..78
FT /evidence="ECO:0007829|PDB:2VCT"
FT HELIX 86..108
FT /evidence="ECO:0007829|PDB:2VCT"
FT HELIX 109..111
FT /evidence="ECO:0007829|PDB:2VCT"
FT TURN 114..116
FT /evidence="ECO:0007829|PDB:2VCT"
FT HELIX 117..130
FT /evidence="ECO:0007829|PDB:2VCT"
FT HELIX 132..143
FT /evidence="ECO:0007829|PDB:2VCT"
FT STRAND 146..149
FT /evidence="ECO:0007829|PDB:2VCT"
FT HELIX 155..170
FT /evidence="ECO:0007829|PDB:2VCT"
FT TURN 172..177
FT /evidence="ECO:0007829|PDB:2VCT"
FT HELIX 179..190
FT /evidence="ECO:0007829|PDB:2VCT"
FT HELIX 192..197
FT /evidence="ECO:0007829|PDB:2VCT"
FT HELIX 210..220
FT /evidence="ECO:0007829|PDB:2VCT"
SQ SEQUENCE 222 AA; 25664 MW; 2823565A693A30AC CRC64;
MAEKPKLHYS NIRGRMESIR WLLAAAGVEF EEKFIKSAED LDKLRNDGYL MFQQVPMVEI
DGMKLVQTRA ILNYIASKYN LYGKDIKEKA LIDMYIEGIA DLGEMILLLP FSQPEEQDAK
LALIQEKTKN RYFPAFEKVL KSHGQDYLVG NKLSRADIHL VELLYYVEEL DSSLISSFPL
LKALKTRISN LPTVKKFLQP GSPRKPPMDE KSLEESRKIF RF
