Full text data of GSTP1
GSTP1
(FAEES3, GST3)
[Confidence: medium (present in either hRBCD or BSc_CH or PM22954596)]
Glutathione S-transferase P; 2.5.1.18 (GST class-pi; GSTP1-1)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
Glutathione S-transferase P; 2.5.1.18 (GST class-pi; GSTP1-1)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
hRBCD
IPI00219757
IPI00219757 Glutathione S-transferase P Conjugation of reduced glutathione to a wide number of exogenous and endogenous hydrophobic electrophiles, RX + glutathione = HX + R-S-glutathione. soluble n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a cytoplasmic n/a found at its expected molecular weight found at molecular weight
IPI00219757 Glutathione S-transferase P Conjugation of reduced glutathione to a wide number of exogenous and endogenous hydrophobic electrophiles, RX + glutathione = HX + R-S-glutathione. soluble n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a cytoplasmic n/a found at its expected molecular weight found at molecular weight
UniProt
P09211
ID GSTP1_HUMAN Reviewed; 210 AA.
AC P09211; O00460; Q15690; Q5TZY3;
DT 01-JUL-1989, integrated into UniProtKB/Swiss-Prot.
read moreDT 23-JAN-2007, sequence version 2.
DT 22-JAN-2014, entry version 169.
DE RecName: Full=Glutathione S-transferase P;
DE EC=2.5.1.18;
DE AltName: Full=GST class-pi;
DE AltName: Full=GSTP1-1;
GN Name=GSTP1; Synonyms=FAEES3, GST3;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=3664469;
RA Kano T., Sakai M., Muramatsu M.;
RT "Structure and expression of a human class pi glutathione S-
RT transferase messenger RNA.";
RL Cancer Res. 47:5626-5630(1987).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=3196325;
RA Cowell I.G., Dixon K.H., Pemble S.E., Ketterer B., Taylor J.B.;
RT "The structure of the human glutathione S-transferase pi gene.";
RL Biochem. J. 255:79-83(1988).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=2542132; DOI=10.1016/0378-1119(89)90377-6;
RA Morrow C.S., Cowan K.H., Goldsmith M.E.;
RT "Structure of the human genomic glutathione S-transferase-pi gene.";
RL Gene 75:3-11(1989).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=2466554;
RA Moscow J.A., Fairchild C.R., Madden M.J., Ransom D.T., Wieand H.S.,
RA O'Brien E.E., Poplack D.G., Cossman J., Myers C.E., Cowan K.H.;
RT "Expression of anionic glutathione-S-transferase and P-glycoprotein
RT genes in human tissues and tumors.";
RL Cancer Res. 49:1422-1428(1989).
RN [5]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RA Bora P.S., Smith C., Lange L.G., Bora N.S., Jones C., Gerhard D.S.;
RT "Human fatty acid ethyl ester synthase III gene: genomic organization,
RT nucleotide sequence, genetic and chromosomal sublocalization.";
RL Submitted (JUL-1994) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [MRNA], AND VARIANTS VAL-105 AND VAL-114.
RX PubMed=9092542; DOI=10.1074/jbc.272.15.10004;
RA Ali-Osman F., Akande O., Antoun G., Mao J.X., Buolamwini J.;
RT "Molecular cloning, characterization, and expression in Escherichia
RT coli of full-length cDNAs of three human glutathione S-transferase Pi
RT gene variants. Evidence for differential catalytic activity of the
RT encoded proteins.";
RL J. Biol. Chem. 272:10004-10012(1997).
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RA Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S.,
RA Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y.,
RA Phelan M., Farmer A.;
RT "Cloning of human full-length CDSs in BD Creator(TM) system donor
RT vector.";
RL Submitted (OCT-2004) to the EMBL/GenBank/DDBJ databases.
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RA Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B.;
RT "Cloning of human full open reading frames in Gateway(TM) system entry
RT vector (pDONR201).";
RL Submitted (MAY-2004) to the EMBL/GenBank/DDBJ databases.
RN [9]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS VAL-105 AND VAL-114.
RG NIEHS SNPs program;
RL Submitted (JUN-2003) to the EMBL/GenBank/DDBJ databases.
RN [10]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT VAL-105.
RC TISSUE=Urinary bladder;
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
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [11]
RP PROTEIN SEQUENCE OF 2-24.
RX PubMed=3979555; DOI=10.1016/0014-5793(85)80324-0;
RA Alin P., Mannervik B., Joernvall H.;
RT "Structural evidence for three different types of glutathione
RT transferase in human tissues.";
RL FEBS Lett. 182:319-322(1985).
RN [12]
RP PROTEIN SEQUENCE OF 2-24.
RX PubMed=3864155; DOI=10.1073/pnas.82.21.7202;
RA Mannervik B., Alin P., Guthenberg C., Jensson H., Tahir M.K.,
RA Warholm M., Joernvall H.;
RT "Identification of three classes of cytosolic glutathione transferase
RT common to several mammalian species: correlation between structural
RT data and enzymatic properties.";
RL Proc. Natl. Acad. Sci. U.S.A. 82:7202-7206(1985).
RN [13]
RP PROTEIN SEQUENCE OF 2-14.
RX PubMed=3395118; DOI=10.1016/0003-9861(88)90564-4;
RA Singh S.V., Ahmad H., Kurosky A., Awasthi Y.C.;
RT "Purification and characterization of unique glutathione S-
RT transferases from human muscle.";
RL Arch. Biochem. Biophys. 264:13-22(1988).
RN [14]
RP PROTEIN SEQUENCE OF 2-12.
RC TISSUE=Platelet;
RX PubMed=12665801; DOI=10.1038/nbt810;
RA Gevaert K., Goethals M., Martens L., Van Damme J., Staes A.,
RA Thomas G.R., Vandekerckhove J.;
RT "Exploring proteomes and analyzing protein processing by mass
RT spectrometric identification of sorted N-terminal peptides.";
RL Nat. Biotechnol. 21:566-569(2003).
RN [15]
RP PROTEIN SEQUENCE OF 2-12; 20-71; 76-101; 104-141; 122-141 AND 192-209,
RP AND MASS SPECTROMETRY.
RC TISSUE=Brain, Cajal-Retzius cell, and Fetal brain cortex;
RA Lubec G., Vishwanath V., Chen W.-Q., Sun Y.;
RL Submitted (DEC-2008) to UniProtKB.
RN [16]
RP PARTIAL PROTEIN SEQUENCE.
RC TISSUE=Colon carcinoma;
RX PubMed=9150948; DOI=10.1002/elps.1150180344;
RA Ji H., Reid G.E., Moritz R.L., Eddes J.S., Burgess A.W., Simpson R.J.;
RT "A two-dimensional gel database of human colon carcinoma proteins.";
RL Electrophoresis 18:605-613(1997).
RN [17]
RP PRIMARY AND SECONDARY STRUCTURAL ANALYZES.
RX PubMed=2327795; DOI=10.1016/0003-9861(90)90277-6;
RA Ahmad H., Wilson D.E., Fritz R.R., Singh S.V., Medh R.D., Nagle G.T.,
RA Awasthi Y.C., Kurosky A.;
RT "Primary and secondary structural analyses of glutathione S-
RT transferase pi from human placenta.";
RL Arch. Biochem. Biophys. 278:398-408(1990).
RN [18]
RP CATALYTIC ACTIVITY, AND MUTAGENESIS OF TYR-8.
RX PubMed=1567427; DOI=10.1016/0006-291X(92)91177-R;
RA Kong K.H., Takasu K., Inoue H., Takahashi K.;
RT "Tyrosine-7 in human class Pi glutathione S-transferase is important
RT for lowering the pKa of the thiol group of glutathione in the enzyme-
RT glutathione complex.";
RL Biochem. Biophys. Res. Commun. 184:194-197(1992).
RN [19]
RP CATALYTIC ACTIVITY, AND MUTAGENESIS OF TYR-8.
RX PubMed=1540159; DOI=10.1016/0006-291X(92)91848-K;
RA Kong K.H., Nishida M., Inoue H., Takahashi K.;
RT "Tyrosine-7 is an essential residue for the catalytic activity of
RT human class PI glutathione S-transferase: chemical modification and
RT site-directed mutagenesis studies.";
RL Biochem. Biophys. Res. Commun. 182:1122-1129(1992).
RN [20]
RP MUTAGENESIS OF ASP-99, AND CATALYTIC ACTIVITY.
RX PubMed=8433974; DOI=10.1093/protein/6.1.93;
RA Kong K.-H., Inoue H., Takahashi K.;
RT "Site-directed mutagenesis study on the roles of evolutionally
RT conserved aspartic acid residues in human glutathione S-transferase
RT P1-1.";
RL Protein Eng. 6:93-99(1993).
RN [21]
RP SUBCELLULAR LOCATION.
RX PubMed=19269317; DOI=10.1016/j.freeradbiomed.2009.02.025;
RA Goto S., Kawakatsu M., Izumi S., Urata Y., Kageyama K., Ihara Y.,
RA Koji T., Kondo T.;
RT "Glutathione S-transferase pi localizes in mitochondria and protects
RT against oxidative stress.";
RL Free Radic. Biol. Med. 46:1392-1403(2009).
RN [22]
RP PHOSPHORYLATION AT TYR-4 AND TYR-199.
RX PubMed=19254954; DOI=10.1074/jbc.M808153200;
RA Okamura T., Singh S., Buolamwini J., Haystead T., Friedman H.,
RA Bigner D., Ali-Osman F.;
RT "Tyrosine phosphorylation of the human glutathione S-transferase P1 by
RT epidermal growth factor receptor.";
RL J. Biol. Chem. 284:16979-16989(2009).
RN [23]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-128, AND MASS SPECTROMETRY.
RX PubMed=19608861; DOI=10.1126/science.1175371;
RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M.,
RA Walther T.C., Olsen J.V., Mann M.;
RT "Lysine acetylation targets protein complexes and co-regulates major
RT cellular functions.";
RL Science 325:834-840(2009).
RN [24]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P.,
RA Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [25]
RP FUNCTION, AND INTERACTION WITH CDK5.
RX PubMed=21668448; DOI=10.1111/j.1471-4159.2011.07343.x;
RA Sun K.H., Chang K.H., Clawson S., Ghosh S., Mirzaei H., Regnier F.,
RA Shah K.;
RT "Glutathione-S-transferase P1 is a critical regulator of Cdk5 kinase
RT activity.";
RL J. Neurochem. 118:902-914(2011).
RN [26]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22814378; DOI=10.1073/pnas.1210303109;
RA Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A.,
RA Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E.,
RA Timmerman E., Prieto J., Arnesen T., Sherman F., Gevaert K.,
RA Aldabe R.;
RT "N-terminal acetylome analyses and functional insights of the N-
RT terminal acetyltransferase NatB.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012).
RN [27]
RP X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS) COMPLEX WITH S-HEXYLGLUTATHIONE.
RX PubMed=1522586; DOI=10.1016/0022-2836(92)90692-D;
RA Reinemer P., Dirr H.W., Ladenstein R., Huber R., Lo Bello M.,
RA Federici G., Parker M.W.;
RT "Three-dimensional structure of class pi glutathione S-transferase
RT from human placenta in complex with S-hexylglutathione at 2.8-A
RT resolution.";
RL J. Mol. Biol. 227:214-226(1992).
RN [28]
RP X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS) IN COMPLEX WITH THE INHIBITOR
RP ETHACRYNIC ACID AND GLUTATHIONE.
RX PubMed=9012673; DOI=10.1021/bi962316i;
RA Oakley A.J., Rossjohn J., Lo Bello M., Caccuri A.M., Federici G.,
RA Parker M.W.;
RT "The three-dimensional structure of the human Pi class glutathione
RT transferase P1-1 in complex with the inhibitor ethacrynic acid and its
RT glutathione conjugate.";
RL Biochemistry 36:576-585(1997).
RN [29]
RP X-RAY CRYSTALLOGRAPHY (1.8 ANGSTROMS) IN COMPLEXES WITH GLUTATHIONE
RP AND INHIBITOR.
RX PubMed=9245401; DOI=10.1021/bi970805s;
RA Ji X., Tordova M., O'Donnell R., Parsons J.F., Hayden J.B.,
RA Gilliland G.L., Zimniak P.;
RT "Structure and function of the xenobiotic substrate-binding site and
RT location of a potential non-substrate-binding site in a class pi
RT glutathione S-transferase.";
RL Biochemistry 36:9690-9702(1997).
RN [30]
RP X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS) IN COMPLEXES WITH GLUTATHIONE.
RX PubMed=9398518; DOI=10.1006/jmbi.1997.1364;
RA Oakley A.J., Lo Bello M., Battistoni A., Ricci G., Rossjohn J.,
RA Villar H.O., Parker M.W.;
RT "The structures of human glutathione transferase P1-1 in complex with
RT glutathione and various inhibitors at high resolution.";
RL J. Mol. Biol. 274:84-100(1997).
RN [31]
RP X-RAY CRYSTALLOGRAPHY (1.8 ANGSTROMS).
RX PubMed=9351803; DOI=10.1016/S0969-2126(97)00281-5;
RA Prade L., Huber R., Manoharan T.H., Fahl W.E., Reuter W.;
RT "Structures of class pi glutathione S-transferase from human placenta
RT in complex with substrate, transition-state analogue and inhibitor.";
RL Structure 5:1287-1295(1997).
RN [32]
RP X-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS).
RX PubMed=10441116; DOI=10.1021/bi990668u;
RA Ji X., Blaszczyk J., Xiao B., O'Donnell R., Hu X., Herzog C.,
RA Singh S.V., Zimniak P.;
RT "Structure and function of residue 104 and water molecules in the
RT xenobiotic substrate-binding site in human glutathione S-transferase
RT P1-1.";
RL Biochemistry 38:10231-10238(1999).
RN [33]
RP STRUCTURE BY NMR.
RX PubMed=9485454; DOI=10.1021/bi971902o;
RA Nicotra M., Paci M., Sette M., Oakley A.J., Parker M.W., Lo Bello M.,
RA Caccuri A.M., Federici G., Ricci G.;
RT "Solution structure of glutathione bound to human glutathione
RT transferase P1-1: comparison of NMR measurements with the crystal
RT structure.";
RL Biochemistry 37:3020-3027(1998).
RN [34]
RP X-RAY CRYSTALLOGRAPHY (1.6 ANGSTROMS).
RX PubMed=19396894; DOI=10.1002/anie.200900185;
RA Ang W.H., Parker L.J., De Luca A., Juillerat-Jeanneret L.,
RA Morton C.J., Lo Bello M., Parker M.W., Dyson P.J.;
RT "Rational design of an organometallic glutathione transferase
RT inhibitor.";
RL Angew. Chem. Int. Ed. 48:3854-3857(2009).
RN [35]
RP X-RAY CRYSTALLOGRAPHY (1.53 ANGSTROMS) OF 2-210.
RX PubMed=19808963; DOI=10.1158/0008-5472.CAN-09-1314;
RA Federici L., Lo Sterzo C., Pezzola S., Di Matteo A., Scaloni F.,
RA Federici G., Caccuri A.M.;
RT "Structural basis for the binding of the anticancer compound 6-(7-
RT nitro-2,1,3-benzoxadiazol-4-ylthio)hexanol to human glutathione s-
RT transferases.";
RL Cancer Res. 69:8025-8034(2009).
CC -!- FUNCTION: Conjugation of reduced glutathione to a wide number of
CC exogenous and endogenous hydrophobic electrophiles. Regulates
CC negatively CDK5 activity via p25/p35 translocation to prevent
CC neurodegeneration.
CC -!- CATALYTIC ACTIVITY: RX + glutathione = HX + R-S-glutathione.
CC -!- SUBUNIT: Homodimer. Interacts with CDK5.
CC -!- INTERACTION:
CC Q12933:TRAF2; NbExp=4; IntAct=EBI-353467, EBI-355744;
CC -!- SUBCELLULAR LOCATION: Cytoplasm. Mitochondrion. Nucleus. Note=The
CC 83 N-terminal amino-acids function as un uncleaved transit
CC peptide, and arginine residues within it are crucial for
CC motochondrial localization.
CC -!- SIMILARITY: Belongs to the GST superfamily. Pi family.
CC -!- SIMILARITY: Contains 1 GST C-terminal domain.
CC -!- SIMILARITY: Contains 1 GST N-terminal domain.
CC -!- WEB RESOURCE: Name=NIEHS-SNPs;
CC URL="http://egp.gs.washington.edu/data/gstp1/";
CC -!- WEB RESOURCE: Name=SHMPD; Note=The Singapore human mutation and
CC polymorphism database;
CC URL="http://shmpd.bii.a-star.edu.sg/gene.php?genestart=A&genename;=GSTP1";
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DR EMBL; X06547; CAA29794.1; -; mRNA.
DR EMBL; M24485; AAA56823.1; -; Genomic_DNA.
DR EMBL; X08058; CAA30847.1; -; Genomic_DNA.
DR EMBL; X08094; CAA30894.1; -; Genomic_DNA.
DR EMBL; X08095; CAA30894.1; JOINED; Genomic_DNA.
DR EMBL; X08096; CAA30894.1; JOINED; Genomic_DNA.
DR EMBL; X15480; CAA33508.1; -; mRNA.
DR EMBL; U12472; AAA64919.1; -; Genomic_DNA.
DR EMBL; U30897; AAC51280.1; -; mRNA.
DR EMBL; U62589; AAC51237.1; -; mRNA.
DR EMBL; U21689; AAC13869.1; -; Genomic_DNA.
DR EMBL; BT019949; AAV38752.1; -; mRNA.
DR EMBL; BT019950; AAV38753.1; -; mRNA.
DR EMBL; CR450361; CAG29357.1; -; mRNA.
DR EMBL; AY324387; AAP72967.1; -; Genomic_DNA.
DR EMBL; BC010915; AAH10915.1; -; mRNA.
DR PIR; A41177; A41177.
DR PIR; JS0153; A37378.
DR RefSeq; NP_000843.1; NM_000852.3.
DR UniGene; Hs.523836; -.
DR PDB; 10GS; X-ray; 2.20 A; A/B=2-210.
DR PDB; 11GS; X-ray; 2.30 A; A/B=1-210.
DR PDB; 12GS; X-ray; 2.10 A; A/B=1-210.
DR PDB; 13GS; X-ray; 1.90 A; A/B=1-210.
DR PDB; 14GS; X-ray; 2.80 A; A/B=2-209.
DR PDB; 16GS; X-ray; 1.90 A; A/B=2-209.
DR PDB; 17GS; X-ray; 1.90 A; A/B=1-210.
DR PDB; 18GS; X-ray; 1.90 A; A/B=2-209.
DR PDB; 19GS; X-ray; 1.90 A; A/B=2-210.
DR PDB; 1AQV; X-ray; 1.94 A; A/B=2-210.
DR PDB; 1AQW; X-ray; 1.80 A; A/B/C/D=2-210.
DR PDB; 1AQX; X-ray; 2.00 A; A/B/C/D=2-210.
DR PDB; 1EOG; X-ray; 2.10 A; A/B=3-210.
DR PDB; 1EOH; X-ray; 2.50 A; A/B/C/D/E/F/G/H=2-210.
DR PDB; 1GSS; X-ray; 2.80 A; A/B=2-210.
DR PDB; 1KBN; X-ray; 2.00 A; A/B=2-209.
DR PDB; 1LBK; X-ray; 1.86 A; A/B=2-202.
DR PDB; 1MD3; X-ray; 2.03 A; A/B=2-209.
DR PDB; 1MD4; X-ray; 2.10 A; A/B=2-209.
DR PDB; 1PGT; X-ray; 1.80 A; A/B=1-210.
DR PDB; 1PX6; X-ray; 2.10 A; A/B=2-209.
DR PDB; 1PX7; X-ray; 2.03 A; A/B=2-209.
DR PDB; 1ZGN; X-ray; 2.10 A; A/B=2-209.
DR PDB; 20GS; X-ray; 2.45 A; A/B=2-209.
DR PDB; 22GS; X-ray; 1.90 A; A/B=1-210.
DR PDB; 2A2R; X-ray; 1.40 A; A/B=2-209.
DR PDB; 2A2S; X-ray; 1.70 A; A/B=2-209.
DR PDB; 2GSS; X-ray; 1.90 A; A/B=2-210.
DR PDB; 2J9H; X-ray; 2.40 A; A/B=2-210.
DR PDB; 2PGT; X-ray; 1.90 A; A/B=1-210.
DR PDB; 3CSH; X-ray; 1.55 A; A/B=2-210.
DR PDB; 3CSI; X-ray; 1.90 A; A/B/C/D=2-210.
DR PDB; 3CSJ; X-ray; 1.90 A; A/B=2-210.
DR PDB; 3DD3; X-ray; 2.25 A; A/B=1-210.
DR PDB; 3DGQ; X-ray; 1.60 A; A/B=1-210.
DR PDB; 3GSS; X-ray; 1.90 A; A/B=2-210.
DR PDB; 3GUS; X-ray; 1.53 A; A/B=2-210.
DR PDB; 3HJM; X-ray; 2.10 A; A/B/C/D=2-210.
DR PDB; 3HJO; X-ray; 1.95 A; A/B=2-210.
DR PDB; 3HKR; X-ray; 1.80 A; A/B=2-210.
DR PDB; 3IE3; X-ray; 1.80 A; A/B=2-210.
DR PDB; 3KM6; X-ray; 2.10 A; A/B=2-210.
DR PDB; 3KMN; X-ray; 1.80 A; A/B=2-210.
DR PDB; 3KMO; X-ray; 2.60 A; A/B=2-210.
DR PDB; 3N9J; X-ray; 1.85 A; A/B=1-210.
DR PDB; 3PGT; X-ray; 2.14 A; A/B=1-210.
DR PDB; 4GSS; X-ray; 2.50 A; A/B=2-209.
DR PDB; 4PGT; X-ray; 2.10 A; A/B=1-210.
DR PDB; 5GSS; X-ray; 1.95 A; A/B=2-210.
DR PDB; 6GSS; X-ray; 1.90 A; A/B=2-210.
DR PDB; 7GSS; X-ray; 2.20 A; A/B=2-210.
DR PDB; 8GSS; X-ray; 1.90 A; A/B/C=2-210.
DR PDB; 9GSS; X-ray; 1.97 A; A/B=2-210.
DR PDBsum; 10GS; -.
DR PDBsum; 11GS; -.
DR PDBsum; 12GS; -.
DR PDBsum; 13GS; -.
DR PDBsum; 14GS; -.
DR PDBsum; 16GS; -.
DR PDBsum; 17GS; -.
DR PDBsum; 18GS; -.
DR PDBsum; 19GS; -.
DR PDBsum; 1AQV; -.
DR PDBsum; 1AQW; -.
DR PDBsum; 1AQX; -.
DR PDBsum; 1EOG; -.
DR PDBsum; 1EOH; -.
DR PDBsum; 1GSS; -.
DR PDBsum; 1KBN; -.
DR PDBsum; 1LBK; -.
DR PDBsum; 1MD3; -.
DR PDBsum; 1MD4; -.
DR PDBsum; 1PGT; -.
DR PDBsum; 1PX6; -.
DR PDBsum; 1PX7; -.
DR PDBsum; 1ZGN; -.
DR PDBsum; 20GS; -.
DR PDBsum; 22GS; -.
DR PDBsum; 2A2R; -.
DR PDBsum; 2A2S; -.
DR PDBsum; 2GSS; -.
DR PDBsum; 2J9H; -.
DR PDBsum; 2PGT; -.
DR PDBsum; 3CSH; -.
DR PDBsum; 3CSI; -.
DR PDBsum; 3CSJ; -.
DR PDBsum; 3DD3; -.
DR PDBsum; 3DGQ; -.
DR PDBsum; 3GSS; -.
DR PDBsum; 3GUS; -.
DR PDBsum; 3HJM; -.
DR PDBsum; 3HJO; -.
DR PDBsum; 3HKR; -.
DR PDBsum; 3IE3; -.
DR PDBsum; 3KM6; -.
DR PDBsum; 3KMN; -.
DR PDBsum; 3KMO; -.
DR PDBsum; 3N9J; -.
DR PDBsum; 3PGT; -.
DR PDBsum; 4GSS; -.
DR PDBsum; 4PGT; -.
DR PDBsum; 5GSS; -.
DR PDBsum; 6GSS; -.
DR PDBsum; 7GSS; -.
DR PDBsum; 8GSS; -.
DR PDBsum; 9GSS; -.
DR ProteinModelPortal; P09211; -.
DR SMR; P09211; 1-210.
DR IntAct; P09211; 23.
DR MINT; MINT-4998983; -.
DR STRING; 9606.ENSP00000381607; -.
DR BindingDB; P09211; -.
DR ChEMBL; CHEMBL3902; -.
DR DrugBank; DB00903; Ethacrynic acid.
DR DrugBank; DB00143; Glutathione.
DR PhosphoSite; P09211; -.
DR DMDM; 121746; -.
DR DOSAC-COBS-2DPAGE; P09211; -.
DR OGP; P09211; -.
DR REPRODUCTION-2DPAGE; IPI00219757; -.
DR SWISS-2DPAGE; P09211; -.
DR UCD-2DPAGE; P09211; -.
DR PaxDb; P09211; -.
DR PRIDE; P09211; -.
DR DNASU; 2950; -.
DR Ensembl; ENST00000398606; ENSP00000381607; ENSG00000084207.
DR GeneID; 2950; -.
DR KEGG; hsa:2950; -.
DR UCSC; uc001omf.3; human.
DR CTD; 2950; -.
DR GeneCards; GC11P067351; -.
DR HGNC; HGNC:4638; GSTP1.
DR HPA; CAB019298; -.
DR HPA; HPA019779; -.
DR HPA; HPA019869; -.
DR MIM; 134660; gene.
DR neXtProt; NX_P09211; -.
DR PharmGKB; PA29028; -.
DR eggNOG; KOG1695; -.
DR HOGENOM; HOG000115733; -.
DR HOVERGEN; HBG108324; -.
DR InParanoid; P09211; -.
DR KO; K00799; -.
DR OMA; DLRCKYV; -.
DR OrthoDB; EOG7KH9M3; -.
DR Reactome; REACT_111217; Metabolism.
DR SABIO-RK; P09211; -.
DR ChiTaRS; GSTP1; human.
DR EvolutionaryTrace; P09211; -.
DR GeneWiki; GSTP1; -.
DR GenomeRNAi; 2950; -.
DR NextBio; 11692; -.
DR PMAP-CutDB; P09211; -.
DR PRO; PR:P09211; -.
DR ArrayExpress; P09211; -.
DR Bgee; P09211; -.
DR CleanEx; HS_GSTP1; -.
DR Genevestigator; P09211; -.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0005739; C:mitochondrion; IEA:UniProtKB-SubCell.
DR GO; GO:0005634; C:nucleus; IEA:UniProtKB-SubCell.
DR GO; GO:0097057; C:TRAF2-GSTP1 complex; IDA:BHF-UCL.
DR GO; GO:0035731; F:dinitrosyl-iron complex binding; IDA:BHF-UCL.
DR GO; GO:0004364; F:glutathione transferase activity; IDA:UniProtKB.
DR GO; GO:0008432; F:JUN kinase binding; ISS:BHF-UCL.
DR GO; GO:0019207; F:kinase regulator activity; ISS:BHF-UCL.
DR GO; GO:0070026; F:nitric oxide binding; NAS:BHF-UCL.
DR GO; GO:0035730; F:S-nitrosoglutathione binding; IDA:BHF-UCL.
DR GO; GO:0071222; P:cellular response to lipopolysaccharide; ISS:BHF-UCL.
DR GO; GO:0007417; P:central nervous system development; TAS:ProtInc.
DR GO; GO:0035726; P:common myeloid progenitor cell proliferation; ISS:BHF-UCL.
DR GO; GO:1901687; P:glutathione derivative biosynthetic process; TAS:Reactome.
DR GO; GO:0006749; P:glutathione metabolic process; IDA:UniProtKB.
DR GO; GO:0002674; P:negative regulation of acute inflammatory response; NAS:BHF-UCL.
DR GO; GO:0043066; P:negative regulation of apoptotic process; TAS:UniProtKB.
DR GO; GO:0070373; P:negative regulation of ERK1 and ERK2 cascade; IDA:BHF-UCL.
DR GO; GO:2001237; P:negative regulation of extrinsic apoptotic signaling pathway; IDA:BHF-UCL.
DR GO; GO:0048147; P:negative regulation of fibroblast proliferation; ISS:BHF-UCL.
DR GO; GO:0043124; P:negative regulation of I-kappaB kinase/NF-kappaB cascade; ISS:BHF-UCL.
DR GO; GO:0032691; P:negative regulation of interleukin-1 beta production; IDA:BHF-UCL.
DR GO; GO:0043508; P:negative regulation of JUN kinase activity; IDA:BHF-UCL.
DR GO; GO:0070664; P:negative regulation of leukocyte proliferation; ISS:BHF-UCL.
DR GO; GO:0071638; P:negative regulation of monocyte chemotactic protein-1 production; IDA:BHF-UCL.
DR GO; GO:0060547; P:negative regulation of necrotic cell death; ISS:BHF-UCL.
DR GO; GO:0051771; P:negative regulation of nitric-oxide synthase biosynthetic process; IDA:BHF-UCL.
DR GO; GO:0032873; P:negative regulation of stress-activated MAPK cascade; ISS:BHF-UCL.
DR GO; GO:0032720; P:negative regulation of tumor necrosis factor production; IDA:BHF-UCL.
DR GO; GO:0010804; P:negative regulation of tumor necrosis factor-mediated signaling pathway; IC:BHF-UCL.
DR GO; GO:0035732; P:nitric oxide storage; NAS:BHF-UCL.
DR GO; GO:0032930; P:positive regulation of superoxide anion generation; ISS:BHF-UCL.
DR GO; GO:0000302; P:response to reactive oxygen species; ISS:BHF-UCL.
DR GO; GO:0006805; P:xenobiotic metabolic process; IDA:UniProtKB.
DR Gene3D; 1.20.1050.10; -; 1.
DR Gene3D; 3.40.30.10; -; 1.
DR InterPro; IPR010987; Glutathione-S-Trfase_C-like.
DR InterPro; IPR004045; Glutathione_S-Trfase_N.
DR InterPro; IPR004046; GST_C.
DR InterPro; IPR003082; GST_pi.
DR InterPro; IPR012336; Thioredoxin-like_fold.
DR Pfam; PF00043; GST_C; 1.
DR Pfam; PF02798; GST_N; 1.
DR PRINTS; PR01268; GSTRNSFRASEP.
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; Complete proteome; Cytoplasm;
KW Direct protein sequencing; Mitochondrion; Nucleus; Phosphoprotein;
KW Polymorphism; Reference proteome; Transferase.
FT INIT_MET 1 1 Removed.
FT CHAIN 2 210 Glutathione S-transferase P.
FT /FTId=PRO_0000185900.
FT DOMAIN 2 81 GST N-terminal.
FT DOMAIN 83 204 GST C-terminal.
FT REGION 52 53 Glutathione binding.
FT REGION 65 66 Glutathione binding.
FT BINDING 8 8 Glutathione.
FT BINDING 14 14 Glutathione.
FT BINDING 39 39 Glutathione.
FT BINDING 45 45 Glutathione (By similarity).
FT MOD_RES 4 4 Phosphotyrosine; by EGFR.
FT MOD_RES 128 128 N6-acetyllysine.
FT MOD_RES 199 199 Phosphotyrosine; by EGFR.
FT VARIANT 105 105 I -> V (in allele GSTP1*B and allele
FT GSTP1*C; dbSNP:rs1695).
FT /FTId=VAR_014499.
FT VARIANT 114 114 A -> V (in allele GSTP1*C;
FT dbSNP:rs1138272).
FT /FTId=VAR_014500.
FT VARIANT 169 169 G -> D (in dbSNP:rs41462048).
FT /FTId=VAR_049493.
FT MUTAGEN 8 8 Y->F: Reduces catalytic activity about
FT 50-fold.
FT MUTAGEN 99 99 D->A: Reduces affinity for glutathione.
FT Slightly reduced catalytic activity.
FT CONFLICT 186 186 A -> P (in Ref. 2; CAA30894).
FT STRAND 3 8
FT STRAND 10 12
FT HELIX 13 15
FT HELIX 16 24
FT STRAND 29 33
FT HELIX 36 41
FT HELIX 43 47
FT STRAND 48 51
FT STRAND 55 58
FT STRAND 61 64
FT HELIX 66 76
FT HELIX 84 110
FT HELIX 112 135
FT HELIX 138 140
FT STRAND 144 148
FT HELIX 151 166
FT HELIX 170 173
FT HELIX 175 185
FT HELIX 188 195
FT HELIX 197 200
FT STRAND 204 208
SQ SEQUENCE 210 AA; 23356 MW; 409E33FFAA338396 CRC64;
MPPYTVVYFP VRGRCAALRM LLADQGQSWK EEVVTVETWQ EGSLKASCLY GQLPKFQDGD
LTLYQSNTIL RHLGRTLGLY GKDQQEAALV DMVNDGVEDL RCKYISLIYT NYEAGKDDYV
KALPGQLKPF ETLLSQNQGG KTFIVGDQIS FADYNLLDLL LIHEVLAPGC LDAFPLLSAY
VGRLSARPKL KAFLASPEYV NLPINGNGKQ
//
ID GSTP1_HUMAN Reviewed; 210 AA.
AC P09211; O00460; Q15690; Q5TZY3;
DT 01-JUL-1989, integrated into UniProtKB/Swiss-Prot.
read moreDT 23-JAN-2007, sequence version 2.
DT 22-JAN-2014, entry version 169.
DE RecName: Full=Glutathione S-transferase P;
DE EC=2.5.1.18;
DE AltName: Full=GST class-pi;
DE AltName: Full=GSTP1-1;
GN Name=GSTP1; Synonyms=FAEES3, GST3;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=3664469;
RA Kano T., Sakai M., Muramatsu M.;
RT "Structure and expression of a human class pi glutathione S-
RT transferase messenger RNA.";
RL Cancer Res. 47:5626-5630(1987).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=3196325;
RA Cowell I.G., Dixon K.H., Pemble S.E., Ketterer B., Taylor J.B.;
RT "The structure of the human glutathione S-transferase pi gene.";
RL Biochem. J. 255:79-83(1988).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=2542132; DOI=10.1016/0378-1119(89)90377-6;
RA Morrow C.S., Cowan K.H., Goldsmith M.E.;
RT "Structure of the human genomic glutathione S-transferase-pi gene.";
RL Gene 75:3-11(1989).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=2466554;
RA Moscow J.A., Fairchild C.R., Madden M.J., Ransom D.T., Wieand H.S.,
RA O'Brien E.E., Poplack D.G., Cossman J., Myers C.E., Cowan K.H.;
RT "Expression of anionic glutathione-S-transferase and P-glycoprotein
RT genes in human tissues and tumors.";
RL Cancer Res. 49:1422-1428(1989).
RN [5]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RA Bora P.S., Smith C., Lange L.G., Bora N.S., Jones C., Gerhard D.S.;
RT "Human fatty acid ethyl ester synthase III gene: genomic organization,
RT nucleotide sequence, genetic and chromosomal sublocalization.";
RL Submitted (JUL-1994) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [MRNA], AND VARIANTS VAL-105 AND VAL-114.
RX PubMed=9092542; DOI=10.1074/jbc.272.15.10004;
RA Ali-Osman F., Akande O., Antoun G., Mao J.X., Buolamwini J.;
RT "Molecular cloning, characterization, and expression in Escherichia
RT coli of full-length cDNAs of three human glutathione S-transferase Pi
RT gene variants. Evidence for differential catalytic activity of the
RT encoded proteins.";
RL J. Biol. Chem. 272:10004-10012(1997).
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RA Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S.,
RA Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y.,
RA Phelan M., Farmer A.;
RT "Cloning of human full-length CDSs in BD Creator(TM) system donor
RT vector.";
RL Submitted (OCT-2004) to the EMBL/GenBank/DDBJ databases.
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RA Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B.;
RT "Cloning of human full open reading frames in Gateway(TM) system entry
RT vector (pDONR201).";
RL Submitted (MAY-2004) to the EMBL/GenBank/DDBJ databases.
RN [9]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS VAL-105 AND VAL-114.
RG NIEHS SNPs program;
RL Submitted (JUN-2003) to the EMBL/GenBank/DDBJ databases.
RN [10]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT VAL-105.
RC TISSUE=Urinary bladder;
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
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [11]
RP PROTEIN SEQUENCE OF 2-24.
RX PubMed=3979555; DOI=10.1016/0014-5793(85)80324-0;
RA Alin P., Mannervik B., Joernvall H.;
RT "Structural evidence for three different types of glutathione
RT transferase in human tissues.";
RL FEBS Lett. 182:319-322(1985).
RN [12]
RP PROTEIN SEQUENCE OF 2-24.
RX PubMed=3864155; DOI=10.1073/pnas.82.21.7202;
RA Mannervik B., Alin P., Guthenberg C., Jensson H., Tahir M.K.,
RA Warholm M., Joernvall H.;
RT "Identification of three classes of cytosolic glutathione transferase
RT common to several mammalian species: correlation between structural
RT data and enzymatic properties.";
RL Proc. Natl. Acad. Sci. U.S.A. 82:7202-7206(1985).
RN [13]
RP PROTEIN SEQUENCE OF 2-14.
RX PubMed=3395118; DOI=10.1016/0003-9861(88)90564-4;
RA Singh S.V., Ahmad H., Kurosky A., Awasthi Y.C.;
RT "Purification and characterization of unique glutathione S-
RT transferases from human muscle.";
RL Arch. Biochem. Biophys. 264:13-22(1988).
RN [14]
RP PROTEIN SEQUENCE OF 2-12.
RC TISSUE=Platelet;
RX PubMed=12665801; DOI=10.1038/nbt810;
RA Gevaert K., Goethals M., Martens L., Van Damme J., Staes A.,
RA Thomas G.R., Vandekerckhove J.;
RT "Exploring proteomes and analyzing protein processing by mass
RT spectrometric identification of sorted N-terminal peptides.";
RL Nat. Biotechnol. 21:566-569(2003).
RN [15]
RP PROTEIN SEQUENCE OF 2-12; 20-71; 76-101; 104-141; 122-141 AND 192-209,
RP AND MASS SPECTROMETRY.
RC TISSUE=Brain, Cajal-Retzius cell, and Fetal brain cortex;
RA Lubec G., Vishwanath V., Chen W.-Q., Sun Y.;
RL Submitted (DEC-2008) to UniProtKB.
RN [16]
RP PARTIAL PROTEIN SEQUENCE.
RC TISSUE=Colon carcinoma;
RX PubMed=9150948; DOI=10.1002/elps.1150180344;
RA Ji H., Reid G.E., Moritz R.L., Eddes J.S., Burgess A.W., Simpson R.J.;
RT "A two-dimensional gel database of human colon carcinoma proteins.";
RL Electrophoresis 18:605-613(1997).
RN [17]
RP PRIMARY AND SECONDARY STRUCTURAL ANALYZES.
RX PubMed=2327795; DOI=10.1016/0003-9861(90)90277-6;
RA Ahmad H., Wilson D.E., Fritz R.R., Singh S.V., Medh R.D., Nagle G.T.,
RA Awasthi Y.C., Kurosky A.;
RT "Primary and secondary structural analyses of glutathione S-
RT transferase pi from human placenta.";
RL Arch. Biochem. Biophys. 278:398-408(1990).
RN [18]
RP CATALYTIC ACTIVITY, AND MUTAGENESIS OF TYR-8.
RX PubMed=1567427; DOI=10.1016/0006-291X(92)91177-R;
RA Kong K.H., Takasu K., Inoue H., Takahashi K.;
RT "Tyrosine-7 in human class Pi glutathione S-transferase is important
RT for lowering the pKa of the thiol group of glutathione in the enzyme-
RT glutathione complex.";
RL Biochem. Biophys. Res. Commun. 184:194-197(1992).
RN [19]
RP CATALYTIC ACTIVITY, AND MUTAGENESIS OF TYR-8.
RX PubMed=1540159; DOI=10.1016/0006-291X(92)91848-K;
RA Kong K.H., Nishida M., Inoue H., Takahashi K.;
RT "Tyrosine-7 is an essential residue for the catalytic activity of
RT human class PI glutathione S-transferase: chemical modification and
RT site-directed mutagenesis studies.";
RL Biochem. Biophys. Res. Commun. 182:1122-1129(1992).
RN [20]
RP MUTAGENESIS OF ASP-99, AND CATALYTIC ACTIVITY.
RX PubMed=8433974; DOI=10.1093/protein/6.1.93;
RA Kong K.-H., Inoue H., Takahashi K.;
RT "Site-directed mutagenesis study on the roles of evolutionally
RT conserved aspartic acid residues in human glutathione S-transferase
RT P1-1.";
RL Protein Eng. 6:93-99(1993).
RN [21]
RP SUBCELLULAR LOCATION.
RX PubMed=19269317; DOI=10.1016/j.freeradbiomed.2009.02.025;
RA Goto S., Kawakatsu M., Izumi S., Urata Y., Kageyama K., Ihara Y.,
RA Koji T., Kondo T.;
RT "Glutathione S-transferase pi localizes in mitochondria and protects
RT against oxidative stress.";
RL Free Radic. Biol. Med. 46:1392-1403(2009).
RN [22]
RP PHOSPHORYLATION AT TYR-4 AND TYR-199.
RX PubMed=19254954; DOI=10.1074/jbc.M808153200;
RA Okamura T., Singh S., Buolamwini J., Haystead T., Friedman H.,
RA Bigner D., Ali-Osman F.;
RT "Tyrosine phosphorylation of the human glutathione S-transferase P1 by
RT epidermal growth factor receptor.";
RL J. Biol. Chem. 284:16979-16989(2009).
RN [23]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-128, AND MASS SPECTROMETRY.
RX PubMed=19608861; DOI=10.1126/science.1175371;
RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M.,
RA Walther T.C., Olsen J.V., Mann M.;
RT "Lysine acetylation targets protein complexes and co-regulates major
RT cellular functions.";
RL Science 325:834-840(2009).
RN [24]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P.,
RA Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [25]
RP FUNCTION, AND INTERACTION WITH CDK5.
RX PubMed=21668448; DOI=10.1111/j.1471-4159.2011.07343.x;
RA Sun K.H., Chang K.H., Clawson S., Ghosh S., Mirzaei H., Regnier F.,
RA Shah K.;
RT "Glutathione-S-transferase P1 is a critical regulator of Cdk5 kinase
RT activity.";
RL J. Neurochem. 118:902-914(2011).
RN [26]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22814378; DOI=10.1073/pnas.1210303109;
RA Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A.,
RA Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E.,
RA Timmerman E., Prieto J., Arnesen T., Sherman F., Gevaert K.,
RA Aldabe R.;
RT "N-terminal acetylome analyses and functional insights of the N-
RT terminal acetyltransferase NatB.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012).
RN [27]
RP X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS) COMPLEX WITH S-HEXYLGLUTATHIONE.
RX PubMed=1522586; DOI=10.1016/0022-2836(92)90692-D;
RA Reinemer P., Dirr H.W., Ladenstein R., Huber R., Lo Bello M.,
RA Federici G., Parker M.W.;
RT "Three-dimensional structure of class pi glutathione S-transferase
RT from human placenta in complex with S-hexylglutathione at 2.8-A
RT resolution.";
RL J. Mol. Biol. 227:214-226(1992).
RN [28]
RP X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS) IN COMPLEX WITH THE INHIBITOR
RP ETHACRYNIC ACID AND GLUTATHIONE.
RX PubMed=9012673; DOI=10.1021/bi962316i;
RA Oakley A.J., Rossjohn J., Lo Bello M., Caccuri A.M., Federici G.,
RA Parker M.W.;
RT "The three-dimensional structure of the human Pi class glutathione
RT transferase P1-1 in complex with the inhibitor ethacrynic acid and its
RT glutathione conjugate.";
RL Biochemistry 36:576-585(1997).
RN [29]
RP X-RAY CRYSTALLOGRAPHY (1.8 ANGSTROMS) IN COMPLEXES WITH GLUTATHIONE
RP AND INHIBITOR.
RX PubMed=9245401; DOI=10.1021/bi970805s;
RA Ji X., Tordova M., O'Donnell R., Parsons J.F., Hayden J.B.,
RA Gilliland G.L., Zimniak P.;
RT "Structure and function of the xenobiotic substrate-binding site and
RT location of a potential non-substrate-binding site in a class pi
RT glutathione S-transferase.";
RL Biochemistry 36:9690-9702(1997).
RN [30]
RP X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS) IN COMPLEXES WITH GLUTATHIONE.
RX PubMed=9398518; DOI=10.1006/jmbi.1997.1364;
RA Oakley A.J., Lo Bello M., Battistoni A., Ricci G., Rossjohn J.,
RA Villar H.O., Parker M.W.;
RT "The structures of human glutathione transferase P1-1 in complex with
RT glutathione and various inhibitors at high resolution.";
RL J. Mol. Biol. 274:84-100(1997).
RN [31]
RP X-RAY CRYSTALLOGRAPHY (1.8 ANGSTROMS).
RX PubMed=9351803; DOI=10.1016/S0969-2126(97)00281-5;
RA Prade L., Huber R., Manoharan T.H., Fahl W.E., Reuter W.;
RT "Structures of class pi glutathione S-transferase from human placenta
RT in complex with substrate, transition-state analogue and inhibitor.";
RL Structure 5:1287-1295(1997).
RN [32]
RP X-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS).
RX PubMed=10441116; DOI=10.1021/bi990668u;
RA Ji X., Blaszczyk J., Xiao B., O'Donnell R., Hu X., Herzog C.,
RA Singh S.V., Zimniak P.;
RT "Structure and function of residue 104 and water molecules in the
RT xenobiotic substrate-binding site in human glutathione S-transferase
RT P1-1.";
RL Biochemistry 38:10231-10238(1999).
RN [33]
RP STRUCTURE BY NMR.
RX PubMed=9485454; DOI=10.1021/bi971902o;
RA Nicotra M., Paci M., Sette M., Oakley A.J., Parker M.W., Lo Bello M.,
RA Caccuri A.M., Federici G., Ricci G.;
RT "Solution structure of glutathione bound to human glutathione
RT transferase P1-1: comparison of NMR measurements with the crystal
RT structure.";
RL Biochemistry 37:3020-3027(1998).
RN [34]
RP X-RAY CRYSTALLOGRAPHY (1.6 ANGSTROMS).
RX PubMed=19396894; DOI=10.1002/anie.200900185;
RA Ang W.H., Parker L.J., De Luca A., Juillerat-Jeanneret L.,
RA Morton C.J., Lo Bello M., Parker M.W., Dyson P.J.;
RT "Rational design of an organometallic glutathione transferase
RT inhibitor.";
RL Angew. Chem. Int. Ed. 48:3854-3857(2009).
RN [35]
RP X-RAY CRYSTALLOGRAPHY (1.53 ANGSTROMS) OF 2-210.
RX PubMed=19808963; DOI=10.1158/0008-5472.CAN-09-1314;
RA Federici L., Lo Sterzo C., Pezzola S., Di Matteo A., Scaloni F.,
RA Federici G., Caccuri A.M.;
RT "Structural basis for the binding of the anticancer compound 6-(7-
RT nitro-2,1,3-benzoxadiazol-4-ylthio)hexanol to human glutathione s-
RT transferases.";
RL Cancer Res. 69:8025-8034(2009).
CC -!- FUNCTION: Conjugation of reduced glutathione to a wide number of
CC exogenous and endogenous hydrophobic electrophiles. Regulates
CC negatively CDK5 activity via p25/p35 translocation to prevent
CC neurodegeneration.
CC -!- CATALYTIC ACTIVITY: RX + glutathione = HX + R-S-glutathione.
CC -!- SUBUNIT: Homodimer. Interacts with CDK5.
CC -!- INTERACTION:
CC Q12933:TRAF2; NbExp=4; IntAct=EBI-353467, EBI-355744;
CC -!- SUBCELLULAR LOCATION: Cytoplasm. Mitochondrion. Nucleus. Note=The
CC 83 N-terminal amino-acids function as un uncleaved transit
CC peptide, and arginine residues within it are crucial for
CC motochondrial localization.
CC -!- SIMILARITY: Belongs to the GST superfamily. Pi family.
CC -!- SIMILARITY: Contains 1 GST C-terminal domain.
CC -!- SIMILARITY: Contains 1 GST N-terminal domain.
CC -!- WEB RESOURCE: Name=NIEHS-SNPs;
CC URL="http://egp.gs.washington.edu/data/gstp1/";
CC -!- WEB RESOURCE: Name=SHMPD; Note=The Singapore human mutation and
CC polymorphism database;
CC URL="http://shmpd.bii.a-star.edu.sg/gene.php?genestart=A&genename;=GSTP1";
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DR EMBL; X06547; CAA29794.1; -; mRNA.
DR EMBL; M24485; AAA56823.1; -; Genomic_DNA.
DR EMBL; X08058; CAA30847.1; -; Genomic_DNA.
DR EMBL; X08094; CAA30894.1; -; Genomic_DNA.
DR EMBL; X08095; CAA30894.1; JOINED; Genomic_DNA.
DR EMBL; X08096; CAA30894.1; JOINED; Genomic_DNA.
DR EMBL; X15480; CAA33508.1; -; mRNA.
DR EMBL; U12472; AAA64919.1; -; Genomic_DNA.
DR EMBL; U30897; AAC51280.1; -; mRNA.
DR EMBL; U62589; AAC51237.1; -; mRNA.
DR EMBL; U21689; AAC13869.1; -; Genomic_DNA.
DR EMBL; BT019949; AAV38752.1; -; mRNA.
DR EMBL; BT019950; AAV38753.1; -; mRNA.
DR EMBL; CR450361; CAG29357.1; -; mRNA.
DR EMBL; AY324387; AAP72967.1; -; Genomic_DNA.
DR EMBL; BC010915; AAH10915.1; -; mRNA.
DR PIR; A41177; A41177.
DR PIR; JS0153; A37378.
DR RefSeq; NP_000843.1; NM_000852.3.
DR UniGene; Hs.523836; -.
DR PDB; 10GS; X-ray; 2.20 A; A/B=2-210.
DR PDB; 11GS; X-ray; 2.30 A; A/B=1-210.
DR PDB; 12GS; X-ray; 2.10 A; A/B=1-210.
DR PDB; 13GS; X-ray; 1.90 A; A/B=1-210.
DR PDB; 14GS; X-ray; 2.80 A; A/B=2-209.
DR PDB; 16GS; X-ray; 1.90 A; A/B=2-209.
DR PDB; 17GS; X-ray; 1.90 A; A/B=1-210.
DR PDB; 18GS; X-ray; 1.90 A; A/B=2-209.
DR PDB; 19GS; X-ray; 1.90 A; A/B=2-210.
DR PDB; 1AQV; X-ray; 1.94 A; A/B=2-210.
DR PDB; 1AQW; X-ray; 1.80 A; A/B/C/D=2-210.
DR PDB; 1AQX; X-ray; 2.00 A; A/B/C/D=2-210.
DR PDB; 1EOG; X-ray; 2.10 A; A/B=3-210.
DR PDB; 1EOH; X-ray; 2.50 A; A/B/C/D/E/F/G/H=2-210.
DR PDB; 1GSS; X-ray; 2.80 A; A/B=2-210.
DR PDB; 1KBN; X-ray; 2.00 A; A/B=2-209.
DR PDB; 1LBK; X-ray; 1.86 A; A/B=2-202.
DR PDB; 1MD3; X-ray; 2.03 A; A/B=2-209.
DR PDB; 1MD4; X-ray; 2.10 A; A/B=2-209.
DR PDB; 1PGT; X-ray; 1.80 A; A/B=1-210.
DR PDB; 1PX6; X-ray; 2.10 A; A/B=2-209.
DR PDB; 1PX7; X-ray; 2.03 A; A/B=2-209.
DR PDB; 1ZGN; X-ray; 2.10 A; A/B=2-209.
DR PDB; 20GS; X-ray; 2.45 A; A/B=2-209.
DR PDB; 22GS; X-ray; 1.90 A; A/B=1-210.
DR PDB; 2A2R; X-ray; 1.40 A; A/B=2-209.
DR PDB; 2A2S; X-ray; 1.70 A; A/B=2-209.
DR PDB; 2GSS; X-ray; 1.90 A; A/B=2-210.
DR PDB; 2J9H; X-ray; 2.40 A; A/B=2-210.
DR PDB; 2PGT; X-ray; 1.90 A; A/B=1-210.
DR PDB; 3CSH; X-ray; 1.55 A; A/B=2-210.
DR PDB; 3CSI; X-ray; 1.90 A; A/B/C/D=2-210.
DR PDB; 3CSJ; X-ray; 1.90 A; A/B=2-210.
DR PDB; 3DD3; X-ray; 2.25 A; A/B=1-210.
DR PDB; 3DGQ; X-ray; 1.60 A; A/B=1-210.
DR PDB; 3GSS; X-ray; 1.90 A; A/B=2-210.
DR PDB; 3GUS; X-ray; 1.53 A; A/B=2-210.
DR PDB; 3HJM; X-ray; 2.10 A; A/B/C/D=2-210.
DR PDB; 3HJO; X-ray; 1.95 A; A/B=2-210.
DR PDB; 3HKR; X-ray; 1.80 A; A/B=2-210.
DR PDB; 3IE3; X-ray; 1.80 A; A/B=2-210.
DR PDB; 3KM6; X-ray; 2.10 A; A/B=2-210.
DR PDB; 3KMN; X-ray; 1.80 A; A/B=2-210.
DR PDB; 3KMO; X-ray; 2.60 A; A/B=2-210.
DR PDB; 3N9J; X-ray; 1.85 A; A/B=1-210.
DR PDB; 3PGT; X-ray; 2.14 A; A/B=1-210.
DR PDB; 4GSS; X-ray; 2.50 A; A/B=2-209.
DR PDB; 4PGT; X-ray; 2.10 A; A/B=1-210.
DR PDB; 5GSS; X-ray; 1.95 A; A/B=2-210.
DR PDB; 6GSS; X-ray; 1.90 A; A/B=2-210.
DR PDB; 7GSS; X-ray; 2.20 A; A/B=2-210.
DR PDB; 8GSS; X-ray; 1.90 A; A/B/C=2-210.
DR PDB; 9GSS; X-ray; 1.97 A; A/B=2-210.
DR PDBsum; 10GS; -.
DR PDBsum; 11GS; -.
DR PDBsum; 12GS; -.
DR PDBsum; 13GS; -.
DR PDBsum; 14GS; -.
DR PDBsum; 16GS; -.
DR PDBsum; 17GS; -.
DR PDBsum; 18GS; -.
DR PDBsum; 19GS; -.
DR PDBsum; 1AQV; -.
DR PDBsum; 1AQW; -.
DR PDBsum; 1AQX; -.
DR PDBsum; 1EOG; -.
DR PDBsum; 1EOH; -.
DR PDBsum; 1GSS; -.
DR PDBsum; 1KBN; -.
DR PDBsum; 1LBK; -.
DR PDBsum; 1MD3; -.
DR PDBsum; 1MD4; -.
DR PDBsum; 1PGT; -.
DR PDBsum; 1PX6; -.
DR PDBsum; 1PX7; -.
DR PDBsum; 1ZGN; -.
DR PDBsum; 20GS; -.
DR PDBsum; 22GS; -.
DR PDBsum; 2A2R; -.
DR PDBsum; 2A2S; -.
DR PDBsum; 2GSS; -.
DR PDBsum; 2J9H; -.
DR PDBsum; 2PGT; -.
DR PDBsum; 3CSH; -.
DR PDBsum; 3CSI; -.
DR PDBsum; 3CSJ; -.
DR PDBsum; 3DD3; -.
DR PDBsum; 3DGQ; -.
DR PDBsum; 3GSS; -.
DR PDBsum; 3GUS; -.
DR PDBsum; 3HJM; -.
DR PDBsum; 3HJO; -.
DR PDBsum; 3HKR; -.
DR PDBsum; 3IE3; -.
DR PDBsum; 3KM6; -.
DR PDBsum; 3KMN; -.
DR PDBsum; 3KMO; -.
DR PDBsum; 3N9J; -.
DR PDBsum; 3PGT; -.
DR PDBsum; 4GSS; -.
DR PDBsum; 4PGT; -.
DR PDBsum; 5GSS; -.
DR PDBsum; 6GSS; -.
DR PDBsum; 7GSS; -.
DR PDBsum; 8GSS; -.
DR PDBsum; 9GSS; -.
DR ProteinModelPortal; P09211; -.
DR SMR; P09211; 1-210.
DR IntAct; P09211; 23.
DR MINT; MINT-4998983; -.
DR STRING; 9606.ENSP00000381607; -.
DR BindingDB; P09211; -.
DR ChEMBL; CHEMBL3902; -.
DR DrugBank; DB00903; Ethacrynic acid.
DR DrugBank; DB00143; Glutathione.
DR PhosphoSite; P09211; -.
DR DMDM; 121746; -.
DR DOSAC-COBS-2DPAGE; P09211; -.
DR OGP; P09211; -.
DR REPRODUCTION-2DPAGE; IPI00219757; -.
DR SWISS-2DPAGE; P09211; -.
DR UCD-2DPAGE; P09211; -.
DR PaxDb; P09211; -.
DR PRIDE; P09211; -.
DR DNASU; 2950; -.
DR Ensembl; ENST00000398606; ENSP00000381607; ENSG00000084207.
DR GeneID; 2950; -.
DR KEGG; hsa:2950; -.
DR UCSC; uc001omf.3; human.
DR CTD; 2950; -.
DR GeneCards; GC11P067351; -.
DR HGNC; HGNC:4638; GSTP1.
DR HPA; CAB019298; -.
DR HPA; HPA019779; -.
DR HPA; HPA019869; -.
DR MIM; 134660; gene.
DR neXtProt; NX_P09211; -.
DR PharmGKB; PA29028; -.
DR eggNOG; KOG1695; -.
DR HOGENOM; HOG000115733; -.
DR HOVERGEN; HBG108324; -.
DR InParanoid; P09211; -.
DR KO; K00799; -.
DR OMA; DLRCKYV; -.
DR OrthoDB; EOG7KH9M3; -.
DR Reactome; REACT_111217; Metabolism.
DR SABIO-RK; P09211; -.
DR ChiTaRS; GSTP1; human.
DR EvolutionaryTrace; P09211; -.
DR GeneWiki; GSTP1; -.
DR GenomeRNAi; 2950; -.
DR NextBio; 11692; -.
DR PMAP-CutDB; P09211; -.
DR PRO; PR:P09211; -.
DR ArrayExpress; P09211; -.
DR Bgee; P09211; -.
DR CleanEx; HS_GSTP1; -.
DR Genevestigator; P09211; -.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0005739; C:mitochondrion; IEA:UniProtKB-SubCell.
DR GO; GO:0005634; C:nucleus; IEA:UniProtKB-SubCell.
DR GO; GO:0097057; C:TRAF2-GSTP1 complex; IDA:BHF-UCL.
DR GO; GO:0035731; F:dinitrosyl-iron complex binding; IDA:BHF-UCL.
DR GO; GO:0004364; F:glutathione transferase activity; IDA:UniProtKB.
DR GO; GO:0008432; F:JUN kinase binding; ISS:BHF-UCL.
DR GO; GO:0019207; F:kinase regulator activity; ISS:BHF-UCL.
DR GO; GO:0070026; F:nitric oxide binding; NAS:BHF-UCL.
DR GO; GO:0035730; F:S-nitrosoglutathione binding; IDA:BHF-UCL.
DR GO; GO:0071222; P:cellular response to lipopolysaccharide; ISS:BHF-UCL.
DR GO; GO:0007417; P:central nervous system development; TAS:ProtInc.
DR GO; GO:0035726; P:common myeloid progenitor cell proliferation; ISS:BHF-UCL.
DR GO; GO:1901687; P:glutathione derivative biosynthetic process; TAS:Reactome.
DR GO; GO:0006749; P:glutathione metabolic process; IDA:UniProtKB.
DR GO; GO:0002674; P:negative regulation of acute inflammatory response; NAS:BHF-UCL.
DR GO; GO:0043066; P:negative regulation of apoptotic process; TAS:UniProtKB.
DR GO; GO:0070373; P:negative regulation of ERK1 and ERK2 cascade; IDA:BHF-UCL.
DR GO; GO:2001237; P:negative regulation of extrinsic apoptotic signaling pathway; IDA:BHF-UCL.
DR GO; GO:0048147; P:negative regulation of fibroblast proliferation; ISS:BHF-UCL.
DR GO; GO:0043124; P:negative regulation of I-kappaB kinase/NF-kappaB cascade; ISS:BHF-UCL.
DR GO; GO:0032691; P:negative regulation of interleukin-1 beta production; IDA:BHF-UCL.
DR GO; GO:0043508; P:negative regulation of JUN kinase activity; IDA:BHF-UCL.
DR GO; GO:0070664; P:negative regulation of leukocyte proliferation; ISS:BHF-UCL.
DR GO; GO:0071638; P:negative regulation of monocyte chemotactic protein-1 production; IDA:BHF-UCL.
DR GO; GO:0060547; P:negative regulation of necrotic cell death; ISS:BHF-UCL.
DR GO; GO:0051771; P:negative regulation of nitric-oxide synthase biosynthetic process; IDA:BHF-UCL.
DR GO; GO:0032873; P:negative regulation of stress-activated MAPK cascade; ISS:BHF-UCL.
DR GO; GO:0032720; P:negative regulation of tumor necrosis factor production; IDA:BHF-UCL.
DR GO; GO:0010804; P:negative regulation of tumor necrosis factor-mediated signaling pathway; IC:BHF-UCL.
DR GO; GO:0035732; P:nitric oxide storage; NAS:BHF-UCL.
DR GO; GO:0032930; P:positive regulation of superoxide anion generation; ISS:BHF-UCL.
DR GO; GO:0000302; P:response to reactive oxygen species; ISS:BHF-UCL.
DR GO; GO:0006805; P:xenobiotic metabolic process; IDA:UniProtKB.
DR Gene3D; 1.20.1050.10; -; 1.
DR Gene3D; 3.40.30.10; -; 1.
DR InterPro; IPR010987; Glutathione-S-Trfase_C-like.
DR InterPro; IPR004045; Glutathione_S-Trfase_N.
DR InterPro; IPR004046; GST_C.
DR InterPro; IPR003082; GST_pi.
DR InterPro; IPR012336; Thioredoxin-like_fold.
DR Pfam; PF00043; GST_C; 1.
DR Pfam; PF02798; GST_N; 1.
DR PRINTS; PR01268; GSTRNSFRASEP.
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; Complete proteome; Cytoplasm;
KW Direct protein sequencing; Mitochondrion; Nucleus; Phosphoprotein;
KW Polymorphism; Reference proteome; Transferase.
FT INIT_MET 1 1 Removed.
FT CHAIN 2 210 Glutathione S-transferase P.
FT /FTId=PRO_0000185900.
FT DOMAIN 2 81 GST N-terminal.
FT DOMAIN 83 204 GST C-terminal.
FT REGION 52 53 Glutathione binding.
FT REGION 65 66 Glutathione binding.
FT BINDING 8 8 Glutathione.
FT BINDING 14 14 Glutathione.
FT BINDING 39 39 Glutathione.
FT BINDING 45 45 Glutathione (By similarity).
FT MOD_RES 4 4 Phosphotyrosine; by EGFR.
FT MOD_RES 128 128 N6-acetyllysine.
FT MOD_RES 199 199 Phosphotyrosine; by EGFR.
FT VARIANT 105 105 I -> V (in allele GSTP1*B and allele
FT GSTP1*C; dbSNP:rs1695).
FT /FTId=VAR_014499.
FT VARIANT 114 114 A -> V (in allele GSTP1*C;
FT dbSNP:rs1138272).
FT /FTId=VAR_014500.
FT VARIANT 169 169 G -> D (in dbSNP:rs41462048).
FT /FTId=VAR_049493.
FT MUTAGEN 8 8 Y->F: Reduces catalytic activity about
FT 50-fold.
FT MUTAGEN 99 99 D->A: Reduces affinity for glutathione.
FT Slightly reduced catalytic activity.
FT CONFLICT 186 186 A -> P (in Ref. 2; CAA30894).
FT STRAND 3 8
FT STRAND 10 12
FT HELIX 13 15
FT HELIX 16 24
FT STRAND 29 33
FT HELIX 36 41
FT HELIX 43 47
FT STRAND 48 51
FT STRAND 55 58
FT STRAND 61 64
FT HELIX 66 76
FT HELIX 84 110
FT HELIX 112 135
FT HELIX 138 140
FT STRAND 144 148
FT HELIX 151 166
FT HELIX 170 173
FT HELIX 175 185
FT HELIX 188 195
FT HELIX 197 200
FT STRAND 204 208
SQ SEQUENCE 210 AA; 23356 MW; 409E33FFAA338396 CRC64;
MPPYTVVYFP VRGRCAALRM LLADQGQSWK EEVVTVETWQ EGSLKASCLY GQLPKFQDGD
LTLYQSNTIL RHLGRTLGLY GKDQQEAALV DMVNDGVEDL RCKYISLIYT NYEAGKDDYV
KALPGQLKPF ETLLSQNQGG KTFIVGDQIS FADYNLLDLL LIHEVLAPGC LDAFPLLSAY
VGRLSARPKL KAFLASPEYV NLPINGNGKQ
//
MIM
134660
*RECORD*
*FIELD* NO
134660
*FIELD* TI
*134660 GLUTATHIONE S-TRANSFERASE, PI; GSTP1
;;GLUTATHIONE S-TRANSFERASE 3; GST3;;
read moreGST, CLASS PI;;
FATTY ACID ETHYL ESTER SYNTHASE III, MYOCARDIAL; FAEES3
GLUTATHIONE S-TRANSFERASE PI PSEUDOGENE, INCLUDED; GSTPP, INCLUDED
*FIELD* TX
DESCRIPTION
Glutathione S-transferases (GSTs; EC 2.5.1.18) are a family of enzymes
that play an important role in detoxification by catalyzing the
conjugation of many hydrophobic and electrophilic compounds with reduced
glutathione. Based on their biochemical, immunologic, and structural
properties, the mammalian cytosolic GSTs are divided into several
classes, including alpha (e.g., 138359), mu (e.g., 138350), kappa
(602321), theta (e.g., 600436), pi, omega (e.g., 605482), and zeta
(e.g., 603758). In addition, there is a class of microsomal GSTs (e.g.,
138330). Each class is encoded by a single gene or a gene family.
CLONING
By screening a human placenta cDNA library with a rat placenta GST
(GSTP) cDNA, Kano et al. (1987) isolated GST-pi cDNAs. The predicted
209-amino acid protein shares 86% sequence identity with GSTP. However,
GST-pi has a pI of 5.5, while that of GSTP is 6.9. Northern
hybridization revealed that GST-pi is expressed as a 750-nucleotide mRNA
in liver. Moscow et al. (1988) cloned cDNA corresponding to the anionic
isozyme of glutathione S-transferase (GST-pi), one of the
drug-detoxifying enzymes overexpressed in multidrug-resistant cells.
Board et al. (1989) isolated a partial cDNA clone of GST3 from a human
lung cDNA library using antiserum to human lung GST3. The sequence
showed 2 base differences from that of GST3 isolated from a human
placenta cDNA library.
Kingsley et al. (1989) and Seldin et al. (1991) concluded that Gsta of
the mouse is homologous to human GST2 (138360), not GST3.
GENE STRUCTURE
Morrow et al. (1989) reported that the GST-pi gene contains 7 exons and
spans approximately 2.8 kb.
MAPPING
Using an X;11 translocation segregating in hybrids, Silberstein et al.
(1982) and Silberstein and Shows (1982) showed that the GST3 gene, which
they called GST1, is located in the p13-qter region of chromosome 11.
Laisney et al. (1983) concluded that the GST gene localized to
chromosome 11 by Silberstein and Shows (1982) was GST3. They assigned
the gene to 11q13-q22. Suzuki and Board (1984) also stated that the
glutathione S-transferase gene that was mapped to chromosome 11 was
GST3, not GST1.
Moscow et al. (1988) and Board et al. (1989) mapped the GST-pi gene to
11q13 using in situ hybridization. Using a panel of human-rodent somatic
cell hybrids and a DNA probe specific for the class, Islam et al. (1989)
mapped GST3, called by them a class pi gene, to chromosome 11. By study
of somatic cell hybrids, Konohana et al. (1990) confirmed the assignment
of the GST3 gene to 11q. Smith et al. (1995) refined the localization of
the GSTP1 gene by study of radiation-reduced somatic cell hybrids. They
identified a tandem repeat polymorphism in the 5-prime region and used
it for linkage analysis to demonstrate that GSTP1 is 5 cM distal to PYGM
(608455) and 4 cM proximal to FGF3 (164950).
Rochelle et al. (1992) indicated that the mouse Gst3 locus is on
proximal chromosome 19.
- Pseudogenes
In in situ hybridization studies that assigned the GSTP1 gene to 11q13,
Board et al. (1989) found an additional hybridizing locus at 12q13-q14.
Board et al. (1992) demonstrated that this closely related Pi class
glutathione S-transferase gene is, in fact, a partial
reverse-transcribed pseudogene.
GENE FUNCTION
Laisney et al. (1984) stated that GST3 is present in all tissues and
cells, with the exception of red cells, in which only erythrocyte GST
(GSTe) is observed. Furthermore, GSTe, the electrophoretically fastest
and most thermolabile of different GSTs analyzed, is found only in
erythrocytes. In leukocytes, only GST3 is found. Beutler et al. (1988),
quoting Board (1981), stated that the enzyme in red cells is designated
GST3 (or GST-rho) and is different from the major liver enzymes GST1 and
GST2 (GSTA2; 138360). The function of the red cell enzyme is not known,
but the red cell membrane contains transport systems that actively
transport glutathione-xenobiotic conjugates from the red cell. Thus, GST
may serve to rid the red cell, and perhaps to scavenge the bloodstream,
of foreign molecules.
Moscow et al. (1989) compared the expression of GST-pi in several normal
and malignant tissues. They found that GST-pi expression was increased
in many tumors relative to matched normal tissue. Konohana et al. (1990)
demonstrated that GST3 is abundantly expressed in human skin.
Bora et al. (1991) identified GST-pi as fatty acid ethyl ester synthase
III (FAEES3), a heart enzyme that metabolizes ethanol nonoxidatively.
Transfection of FAEES3 cDNA into MCF7 cells resulted in a 14-fold
increase in synthase activity and a 12-fold increase in glutathione
S-transferase activity. Transfection of MCF7 cells with placental GST
cDNA resulted in a 13-fold increase in GST activity but no increase in
synthase activity. Board et al. (1993) found that the protein described
by Bora et al. (1991) had no FAEES or GST activity when expressed in E.
coli and suggested that the cDNA may have resulted from a cloning
artifact.
Overdose of acetaminophen, a widely used analgesic drug, can result in
severe hepatotoxicity and is often fatal. This toxic reaction is
associated with metabolic activation by the P450 system to form a
quinoneimine metabolite, which covalently binds to proteins and other
macromolecules to cause cellular damage. At low doses, this metabolite,
NAPQI, is efficiently detoxified, principally by conjugation with
glutathione, a reaction catalyzed in part by the glutathione
S-transferases, including GSTP1. To assess the role of GST in
acetaminophen hepatotoxicity, Henderson et al. (2000) examined
acetaminophen metabolism and liver damage in mice null for Gstp, i.e.,
Gstp1/p2 -/-. Contrary to their expectations, instead of being more
sensitive, the null mice were highly resistant to the hepatotoxic
effects of this compound. The data demonstrated that GSTP does not
contribute in vivo to the formation of glutathione conjugates of
acetaminophen but plays a novel and unexpected role in the toxicity of
this compound.
MOLECULAR GENETICS
Ali-Osman et al. (1997) isolated cDNAs corresponding to 3 polymorphic
GSTP1 alleles, GSTP1*A (134660.0001), GSTP1*B (134660.0002), and GSTP1*C
(134660.0003), expressed in normal cells and malignant gliomas. The
variant cDNAs result from A-to-G and C-to-T transitions at nucleotides
313 and 341, respectively. The transitions changed codon 105 from ATC
(ile) in GSTP1*A to GTC (val) in GSTP1*B and GSTP1*C, and changed codon
114 from GCG (ala) to GTG (val) in GSTP1*C. Both amino acid changes are
in the electrophile-binding active site of the GST-pi peptide. Computer
modeling of the deduced crystal structures of the encoded peptides
showed significant deviations in the interatomic distances of critical
electrophile-binding active site amino acids as a consequence of the
amino acid changes. The encoded proteins expressed in E. coli and
purified by GSH affinity chromatography showed a 3-fold lower K(m) and a
3- to 4-fold higher K(cat)/K(m) for the GSTP1*A-encoded protein than the
proteins encoded by GSTP1*B and GSTP1*C. Analysis of 75 cases showed the
relative frequency of GSTP1*C to be 4-fold higher in malignant gliomas
than in normal tissues. These data provided conclusive molecular
evidence of allelopolymorphism of the human GSTP1 locus, resulting in
active, functionally different GSTP1 proteins, and laid the groundwork
for studies of the role of this gene in xenobiotic metabolism, cancer,
and other human diseases.
Allan et al. (2001) hypothesized that polymorphisms in genes that encode
GSTs alter susceptibility to chemotherapy-induced carcinogenesis,
specifically to therapy-related acute myeloid leukemia (t-AML), a
devastating complication of long-term cancer survival. Elucidation of
genetic determinants may help identify individuals at increased risk of
developing t-AML. To this end, Allan et al. (2001) examined 89 cases of
t-AML, 420 cases of de novo AML, and 1,022 controls for polymorphisms in
these 3 GSTs. Gene deletion of GSTM1 or GSTT1 was not specifically
associated with susceptibility to t-AML. At least 1 GSTP1 valine-105
allele (see 134660.0002 and 134660.0003) was found more often among
t-AML patients with prior exposure to chemotherapy (OR, 2.66),
particularly among those with prior exposure to known GSTP1 substrates
(OR, 4.34), than in patients with de novo AML, and not among those t-AML
patients with prior exposure to radiotherapy alone (OR, 1.01). These
data suggested that inheritance of at least 1 GSTP1 valine-105 allele
confers a significantly increased risk of developing t-AML after
cytotoxic chemotherapy, but not after radiotherapy.
Beutler et al. (1988) found unexplained red cell GST deficiency in an
otherwise healthy adult male with mild hemolytic anemia accompanied by
splenomegaly, indirect hyperbilirubinemia, and cholelithiasis. Residual
enzyme activity was only about 15% of mean normal. Because he was
adopted and childless, the hereditary nature of the defect could not be
established. Modest decreases in leukocyte and platelet GST activities
were documented.
Menegon et al. (1998) pursued the hypotheses that Parkinson disease
(168600) is secondary to the presence of neurotoxins and that pesticides
are possible causative agents. Because glutathione transferases
metabolize xenobiotics, including pesticides, they investigated the role
of GST polymorphisms in the pathogenesis of idiopathic Parkinson
disease. In 95 Parkinson disease patients and 95 controls, they
genotyped PCR polymorphisms in 4 GST classes: GST1, GSTT1 (600436),
GSTP1, and GSTZ1 (603758). Associations were found only with the GSTP1
polymorphisms. Analyzing the genotypes of those subjects who reported
exposure to pesticides (39 patients and 26 controls), they found that
the distribution of genotypes of the GSTP1 polymorphisms differed
significantly between patients and controls. These differences seemed to
be secondary to an excess of heterozygotes and noncarriers of A alleles
among patients. Menegon et al. (1998) interpreted these results as
suggesting that GSTP1, which is expressed in the blood-brain barrier,
may influence response to neurotoxins and explain the susceptibility of
some people to the parkinsonism-inducing effects of pesticides. In a
commentary entitled 'Parkinson's Disease: Nature Meets Nurture,' Golbe
(1998) pointed out that virtually every case-control study investigating
the risk of Parkinson disease has shown that pesticide or herbicide
exposure, or rural or farm experiences, increases Parkinson disease
risk, typically 3-fold or 4-fold. Furthermore, rotenone, a commonly used
pesticide, shares with the active metabolite of MPTP (a known cause of
parkinsonism in humans and laboratory animals) the same neurotoxic
action, namely inhibition of complex I, part of the mitochondrial
respiratory enzyme chain.
Wilk et al. (2006) presented evidence suggesting that exposure to
herbicides may be an effect modifier of the relationship between GSTP1
polymorphisms and age of onset in Parkinson disease.
Zusterzeel et al. (1999) found that GSTP1 is the main GST isoform in
normal placental and decidual tissue. In preeclamptic (189800) women,
they found lower median placental and decidual GSTP1 levels compared to
those in controls. Zusterzeel et al. (1999) suggested that reduced
levels of GSTP1 in preeclampsia may indicate a decreased capacity of the
detoxification system, resulting in a higher susceptibility to
preeclampsia. Among 113 preeclampsia trios (mother, father, and baby),
Zusterzeel et al. (2002) found an increased frequency of the GSTP1
val105 polymorphism (see 134660.0002) in mothers, fathers, and offspring
of preeclamptic pregnancies compared to controls. There was no
significant difference in the GSTP1 allele frequencies in preeclamptic
mothers, fathers, and offspring. The authors emphasized the paternal
contribution to the risk for preeclampsia.
Gilliland et al. (2004) found that GSTP1 and GSTM1 modify the adjuvant
effect of diesel exhaust particles on allergic inflammation. They
challenged ragweed-sensitive patients intranasally with allergen alone
and with allergen plus diesel exhaust particles and found that
individuals with GSTM1 null or GSTP1 ile105 wildtype genotypes showed
significant increases in IgE and histamine after challenge with diesel
exhaust particles and allergens; the increase was largest in patients
with both the GSTP1 ile/ile and GSTM1 null genotypes.
See 606581 for discussion of a possible association between variation in
GSTP1 gene and susceptibility to polysubstance abuse.
*FIELD* AV
.0001
GLUTATHIONE S-TRANSFERASE PI POLYMORPHISM, TYPE A
GSTP1, ILE105 AND ALA114
Ali-Osman et al. (1997) identified 3 polymorphic forms of the GSTP1
gene. One allele, GSTP1*A, has ATC (ile) as codon 105 and GCG (ala) as
codon 114. (Ali-Osman et al. (1997) had designated the substitutions
ILE104 and ALA113 based on then-current numbering.)
.0002
GLUTATHIONE S-TRANSFERASE PI POLYMORPHISM, TYPE B
GSTP1, VAL105 AND ALA114
Ali-Osman et al. (1997) identified 3 polymorphic forms of the GSTP1
gene. One allele, GSTP1*B, has GTC (val) as codon 105 and GCG (ala) as
codon 114. (Ali-Osman et al. (1997) had designated the substitutions
VAL104 and ALA113 based on then-current numbering.)
.0003
GLUTATHIONE S-TRANSFERASE PI POLYMORPHISM, TYPE C
GSTP1, VAL105 AND VAL114
Ali-Osman et al. (1997) identified 3 polymorphic forms of the GSTP1
gene. One allele, GSTP1*C, has GTC (val) as codon 105 and GTG (val) as
codon 114. (Ali-Osman et al. (1997) had designated the substitutions
VAL104 and VAL113 based on then-current numbering.)
*FIELD* SA
Awasthi et al. (1981)
*FIELD* RF
1. Ali-Osman, F.; Akande, O.; Antoun, G.; Mao, J.-X.; Buolamwini,
J.: Molecular cloning, characterization, and expression in Escherichia
coli of full-length cDNAs of three human glutathione S-transferase
Pi gene variants: evidence for differential catalytic activity of
the encoded proteins. J. Biol. Chem. 272: 10004-10012, 1997.
2. Allan, J. M.; Wild, C. P.; Rollinson, S.; Willett, E. V.; Moorman,
A. V.; Dovey, G. J.; Roddam, P. L.; Roman, E.; Cartwright, R. A.;
Morgan, G. J.: Polymorphism in glutathione S-transferase P1 is associated
with susceptibility to chemotherapy-induced leukemia. Proc. Nat.
Acad. Sci. 98: 11592-11597, 2001. Note: Erratum: Proc. Nat. Acad.
Sci. 98: 15394 only, 2001.
3. Awasthi, Y. C.; Dao, D. D.; Partridge, C. A.: Genetic origin of
human glutathione S-transferases. (Abstract) Am. J. Hum. Genet. 33:
35, 1981.
4. Beutler, E.; Dunning, D.; Dabe, I. B.; Forman, L.: Erythrocyte
glutathione S-transferase deficiency and hemolytic anemia. Blood 72:
73-77, 1988.
5. Board, P.; Smith, S.; Green, J.; Coggan, M.; Suzuki, T.: Evidence
against a relationship between fatty acid ethyl ester synthase and
the pi class glutatione S-transferase in humans. J. Biol. Chem. 268:
15655-15658, 1993.
6. Board, P. G.: Biochemical genetics of glutathione-S-transferase
in man. Am. J. Hum. Genet. 33: 36-43, 1981.
7. Board, P. G.; Coggan, M.; Woodcock, D. M.: The human Pi class
glutathione transferase sequence at 12q13-q14 is a reverse-transcribed
pseudogene. Genomics 14: 470-473, 1992.
8. Board, P. G.; Webb, G. C.; Coggan, M.: Isolation of a cDNA clone
and localization of the human glutathione S-transferase 3 genes to
chromosome bands 11q13 and 12q13-14. Ann. Hum. Genet. 53: 205-213,
1989.
9. Bora, P. S.; Bora, N. S.; Wu, X.; Lange, L. G.: Molecular cloning,
sequencing, and expression of human myocardial fatty acid ethyl ester
synthase-III cDNA. J. Biol. Chem. 266: 16774-16777, 1991.
10. Gilliland, F. D.; Li, Y.-F.; Saxon, A.; Diaz-Sanchez, D.: Effect
of glutathione-S-transferase M1 and P1 genotypes on xenobiotic enhancement
of allergic responses: randomised, placebo-controlled crossover study. Lancet 363:
119-125, 2004.
11. Golbe, L. I.: Parkinson's disease: nature meets nurture. Lancet 352:
1328-1329, 1998.
12. Henderson, C. J.; Wolf, C. R.; Kitteringham, N.; Powell, H.; Otto,
D.; Park, B. K.: Increased resistance to acetaminophen hepatotoxicity
in mice lacking glutathione S-transferase Pi. Proc. Nat. Acad. Sci. 97:
12741-12745, 2000.
13. Islam, M. Q.; Platz, A.; Szpirer, J.; Szpirer, C.; Levan, G.;
Mannervik, B.: Chromosomal localization of human glutathione transferase
genes of classes alpha, mu and pi. Hum. Genet. 82: 338-342, 1989.
14. Kano, T.; Sakai, M.; Muramatsu, M.: Structure and expression
of a human class pi glutathione S-transferase messenger RNA. Cancer
Res. 47: 5626-5630, 1987.
15. Kingsley, D. M.; Jenkins, N. A.; Copeland, N. G.: A molecular
genetic linkage map of mouse chromosome 9 with regional localizations
for the Gsta, T3g, Ets-1 and Ldlr loci. Genetics 123: 165-172, 1989.
16. Konohana, A.; Konohana, I.; Schroeder, W. T.; O'Brien, W. R.;
Amagai, M.; Greer, J.; Shimizu, N.; Gammon, W. R.; Siciliano, M. J.;
Duvic, M.: Placental glutathione-S-transferase-pi mRNA is abundantly
expressed in human skin. J. Invest. Derm. 95: 119-126, 1990.
17. Laisney, V.; Van Cong, N.; Gross, M.-S.; Parisi, I.; Foubert,
C.; Weil, D.; Frezal, J.: Localisation du groupe syntenique LDHA-GST3-ESA4
sur le chromosome 11 chez l'homme: analyses des hybrides homme-rongeur
classiques et d'un type nouveau (non adherents a la paroi). Ann.
Genet. 26: 69-74, 1983.
18. Laisney, V.; Van Cong, N.; Gross, M. S.; Frezal, J.: Human genes
for glutathione S-transferases. Hum. Genet. 68: 221-227, 1984.
19. Menegon, A.; Board, P. G.; Blackburn, A. C.; Mellick, G. D.; Le
Couteur, D. G.: Parkinson's disease, pesticides, and glutathione
transferase polymorphisms. Lancet 352: 1344-1346, 1998.
20. Morrow, C. S.; Cowan, K. H.; Goldsmith, M. E.: Structure of the
human genomic glutathione S-transferase-pi gene. Gene 75: 3-11,
1989.
21. Moscow, J. A.; Fairchild, C. R.; Madden, M. J.; Ransom, D. T.;
Wieand, H. S.; O'Brien, E. E.; Poplack, D. G.; Cossman, J.; Myers,
C. E.; Cowan, K. H.: Expression of anionic glutathione-S-transferase
and P-glycoprotein genes in human tissues and tumors. Cancer Res. 49:
1422-1428, 1989.
22. Moscow, J. A.; Townsend, A. J.; Goldsmith, M. E.; Whang-Peng,
J.; Vickers, P. J.; Poisson, R.; Legault-Poisson, S.; Myers, C. E.;
Cowan, K. H.: Isolation of the human anionic glutathione S-transferase
cDNA and the relation of its gene expression to estrogen-receptor
content in primary breast cancer. Proc. Nat. Acad. Sci. 85: 6518-6522,
1988.
23. Rochelle, J. M.; Watson, M. L.; Oakey, R. J.; Seldin, M. F.:
A linkage map of mouse chromosome 19: definition of comparative mapping
relationships with human chromosomes 10 and 11 including the MEN1
locus. Genomics 14: 26-31, 1992.
24. Seldin, M. F.; Saunders, A. M.; Rochelle, J. M.; Howard, T. A.
: A proximal mouse chromosome 9 linkage map that further defines linkage
groups homologous with segments of human chromosomes 11, 15, and 19. Genomics 9:
678-685, 1991.
25. Silberstein, D. L.; Sakaguchi, A. Y.; Shows, T. B.: Assignment
of the gene for glutathione S-transferase-1 (GST1) to human chromosome
11. (Abstract) Cytogenet. Cell Genet. 32: 317, 1982.
26. Silberstein, D. L.; Shows, T. B.: Gene for glutathione S-transferase-1
(GST1) is on human chromosome 11. Somat. Cell Genet. 8: 667-675,
1982.
27. Smith, C. M.; Bora, P. S.; Bora, N. S.; Jones, C.; Gerhard, D.
S.: Genetic and radiation-reduced somatic cell hybrid sublocalization
of the human GSTP1 gene. Cytogenet. Cell Genet. 71: 235-239, 1995.
28. Suzuki, T.; Board, P.: Glutathione-S-transferase gene mapped
to chromosome 11 is GST3 not GST1. (Letter) Somat. Cell Molec. Genet. 10:
319-320, 1984.
29. Wilk, J. B.; Tobin, J. E.; Suchowersky, O.; Shill, H. A.; Klein,
C.; Wooten, G. F.; Lew, M. F.; Mark, M. H.; Guttman, M.; Watts, R.
L.; Singer, C.; Growdon, J. H.; and 26 others: Herbicide exposure
modifies GSTP1 haplotype association to Parkinson onset age: the GenePD
study. Neurology 67: 2206-2210, 2006.
30. Zusterzeel, P. L. M.; Peters, W. H. M.; de Bruyn, M. A. H.; Knapen,
M. F. C. M.; Merkus, H. M. W. M.; Steegers, E. A. P.: Glutathione
S-transferase isoenzymes in decidua and placenta of preeclamptic pregnancies. Obstet.
Gynec. 94: 1033-1038, 1999.
31. Zusterzeel, P. L. M.; te Morsche, R.; Raijmakers, M. T. M.; Roes,
E. M.; Peters, W. H. M.; Steegers, E. A. P.: Paternal contribution
to the risk for pre-eclampsia. J. Med. Genet. 39: 44-45, 2002.
*FIELD* CN
Cassandra L. Kniffin - updated: 12/26/2007
John Logan Black, III - updated: 8/9/2005
Marla J. F. O'Neill - updated: 2/5/2004
Cassandra L. Kniffin - reorganized: 10/19/2003
Cassandra L. Kniffin - updated: 10/17/2003
Victor A. McKusick - updated: 11/1/2001
Victor A. McKusick - updated: 11/30/2000
Victor A. McKusick - updated: 2/3/1999
Rebekah S. Rasooly - updated: 10/7/1998
*FIELD* CD
Victor A. McKusick: 11/15/1991
*FIELD* ED
carol: 11/14/2013
terry: 7/27/2012
carol: 5/25/2012
carol: 9/18/2008
wwang: 1/15/2008
ckniffin: 12/26/2007
carol: 1/10/2006
carol: 12/6/2005
terry: 8/9/2005
carol: 3/9/2004
carol: 2/5/2004
carol: 10/19/2003
ckniffin: 10/17/2003
carol: 11/20/2001
mcapotos: 11/20/2001
mcapotos: 11/16/2001
terry: 11/1/2001
mcapotos: 12/12/2000
mcapotos: 12/6/2000
terry: 11/30/2000
alopez: 4/21/1999
carol: 4/14/1999
terry: 2/9/1999
terry: 2/8/1999
terry: 2/3/1999
alopez: 10/8/1998
alopez: 10/7/1998
supermim: 3/16/1992
carol: 11/15/1991
*RECORD*
*FIELD* NO
134660
*FIELD* TI
*134660 GLUTATHIONE S-TRANSFERASE, PI; GSTP1
;;GLUTATHIONE S-TRANSFERASE 3; GST3;;
read moreGST, CLASS PI;;
FATTY ACID ETHYL ESTER SYNTHASE III, MYOCARDIAL; FAEES3
GLUTATHIONE S-TRANSFERASE PI PSEUDOGENE, INCLUDED; GSTPP, INCLUDED
*FIELD* TX
DESCRIPTION
Glutathione S-transferases (GSTs; EC 2.5.1.18) are a family of enzymes
that play an important role in detoxification by catalyzing the
conjugation of many hydrophobic and electrophilic compounds with reduced
glutathione. Based on their biochemical, immunologic, and structural
properties, the mammalian cytosolic GSTs are divided into several
classes, including alpha (e.g., 138359), mu (e.g., 138350), kappa
(602321), theta (e.g., 600436), pi, omega (e.g., 605482), and zeta
(e.g., 603758). In addition, there is a class of microsomal GSTs (e.g.,
138330). Each class is encoded by a single gene or a gene family.
CLONING
By screening a human placenta cDNA library with a rat placenta GST
(GSTP) cDNA, Kano et al. (1987) isolated GST-pi cDNAs. The predicted
209-amino acid protein shares 86% sequence identity with GSTP. However,
GST-pi has a pI of 5.5, while that of GSTP is 6.9. Northern
hybridization revealed that GST-pi is expressed as a 750-nucleotide mRNA
in liver. Moscow et al. (1988) cloned cDNA corresponding to the anionic
isozyme of glutathione S-transferase (GST-pi), one of the
drug-detoxifying enzymes overexpressed in multidrug-resistant cells.
Board et al. (1989) isolated a partial cDNA clone of GST3 from a human
lung cDNA library using antiserum to human lung GST3. The sequence
showed 2 base differences from that of GST3 isolated from a human
placenta cDNA library.
Kingsley et al. (1989) and Seldin et al. (1991) concluded that Gsta of
the mouse is homologous to human GST2 (138360), not GST3.
GENE STRUCTURE
Morrow et al. (1989) reported that the GST-pi gene contains 7 exons and
spans approximately 2.8 kb.
MAPPING
Using an X;11 translocation segregating in hybrids, Silberstein et al.
(1982) and Silberstein and Shows (1982) showed that the GST3 gene, which
they called GST1, is located in the p13-qter region of chromosome 11.
Laisney et al. (1983) concluded that the GST gene localized to
chromosome 11 by Silberstein and Shows (1982) was GST3. They assigned
the gene to 11q13-q22. Suzuki and Board (1984) also stated that the
glutathione S-transferase gene that was mapped to chromosome 11 was
GST3, not GST1.
Moscow et al. (1988) and Board et al. (1989) mapped the GST-pi gene to
11q13 using in situ hybridization. Using a panel of human-rodent somatic
cell hybrids and a DNA probe specific for the class, Islam et al. (1989)
mapped GST3, called by them a class pi gene, to chromosome 11. By study
of somatic cell hybrids, Konohana et al. (1990) confirmed the assignment
of the GST3 gene to 11q. Smith et al. (1995) refined the localization of
the GSTP1 gene by study of radiation-reduced somatic cell hybrids. They
identified a tandem repeat polymorphism in the 5-prime region and used
it for linkage analysis to demonstrate that GSTP1 is 5 cM distal to PYGM
(608455) and 4 cM proximal to FGF3 (164950).
Rochelle et al. (1992) indicated that the mouse Gst3 locus is on
proximal chromosome 19.
- Pseudogenes
In in situ hybridization studies that assigned the GSTP1 gene to 11q13,
Board et al. (1989) found an additional hybridizing locus at 12q13-q14.
Board et al. (1992) demonstrated that this closely related Pi class
glutathione S-transferase gene is, in fact, a partial
reverse-transcribed pseudogene.
GENE FUNCTION
Laisney et al. (1984) stated that GST3 is present in all tissues and
cells, with the exception of red cells, in which only erythrocyte GST
(GSTe) is observed. Furthermore, GSTe, the electrophoretically fastest
and most thermolabile of different GSTs analyzed, is found only in
erythrocytes. In leukocytes, only GST3 is found. Beutler et al. (1988),
quoting Board (1981), stated that the enzyme in red cells is designated
GST3 (or GST-rho) and is different from the major liver enzymes GST1 and
GST2 (GSTA2; 138360). The function of the red cell enzyme is not known,
but the red cell membrane contains transport systems that actively
transport glutathione-xenobiotic conjugates from the red cell. Thus, GST
may serve to rid the red cell, and perhaps to scavenge the bloodstream,
of foreign molecules.
Moscow et al. (1989) compared the expression of GST-pi in several normal
and malignant tissues. They found that GST-pi expression was increased
in many tumors relative to matched normal tissue. Konohana et al. (1990)
demonstrated that GST3 is abundantly expressed in human skin.
Bora et al. (1991) identified GST-pi as fatty acid ethyl ester synthase
III (FAEES3), a heart enzyme that metabolizes ethanol nonoxidatively.
Transfection of FAEES3 cDNA into MCF7 cells resulted in a 14-fold
increase in synthase activity and a 12-fold increase in glutathione
S-transferase activity. Transfection of MCF7 cells with placental GST
cDNA resulted in a 13-fold increase in GST activity but no increase in
synthase activity. Board et al. (1993) found that the protein described
by Bora et al. (1991) had no FAEES or GST activity when expressed in E.
coli and suggested that the cDNA may have resulted from a cloning
artifact.
Overdose of acetaminophen, a widely used analgesic drug, can result in
severe hepatotoxicity and is often fatal. This toxic reaction is
associated with metabolic activation by the P450 system to form a
quinoneimine metabolite, which covalently binds to proteins and other
macromolecules to cause cellular damage. At low doses, this metabolite,
NAPQI, is efficiently detoxified, principally by conjugation with
glutathione, a reaction catalyzed in part by the glutathione
S-transferases, including GSTP1. To assess the role of GST in
acetaminophen hepatotoxicity, Henderson et al. (2000) examined
acetaminophen metabolism and liver damage in mice null for Gstp, i.e.,
Gstp1/p2 -/-. Contrary to their expectations, instead of being more
sensitive, the null mice were highly resistant to the hepatotoxic
effects of this compound. The data demonstrated that GSTP does not
contribute in vivo to the formation of glutathione conjugates of
acetaminophen but plays a novel and unexpected role in the toxicity of
this compound.
MOLECULAR GENETICS
Ali-Osman et al. (1997) isolated cDNAs corresponding to 3 polymorphic
GSTP1 alleles, GSTP1*A (134660.0001), GSTP1*B (134660.0002), and GSTP1*C
(134660.0003), expressed in normal cells and malignant gliomas. The
variant cDNAs result from A-to-G and C-to-T transitions at nucleotides
313 and 341, respectively. The transitions changed codon 105 from ATC
(ile) in GSTP1*A to GTC (val) in GSTP1*B and GSTP1*C, and changed codon
114 from GCG (ala) to GTG (val) in GSTP1*C. Both amino acid changes are
in the electrophile-binding active site of the GST-pi peptide. Computer
modeling of the deduced crystal structures of the encoded peptides
showed significant deviations in the interatomic distances of critical
electrophile-binding active site amino acids as a consequence of the
amino acid changes. The encoded proteins expressed in E. coli and
purified by GSH affinity chromatography showed a 3-fold lower K(m) and a
3- to 4-fold higher K(cat)/K(m) for the GSTP1*A-encoded protein than the
proteins encoded by GSTP1*B and GSTP1*C. Analysis of 75 cases showed the
relative frequency of GSTP1*C to be 4-fold higher in malignant gliomas
than in normal tissues. These data provided conclusive molecular
evidence of allelopolymorphism of the human GSTP1 locus, resulting in
active, functionally different GSTP1 proteins, and laid the groundwork
for studies of the role of this gene in xenobiotic metabolism, cancer,
and other human diseases.
Allan et al. (2001) hypothesized that polymorphisms in genes that encode
GSTs alter susceptibility to chemotherapy-induced carcinogenesis,
specifically to therapy-related acute myeloid leukemia (t-AML), a
devastating complication of long-term cancer survival. Elucidation of
genetic determinants may help identify individuals at increased risk of
developing t-AML. To this end, Allan et al. (2001) examined 89 cases of
t-AML, 420 cases of de novo AML, and 1,022 controls for polymorphisms in
these 3 GSTs. Gene deletion of GSTM1 or GSTT1 was not specifically
associated with susceptibility to t-AML. At least 1 GSTP1 valine-105
allele (see 134660.0002 and 134660.0003) was found more often among
t-AML patients with prior exposure to chemotherapy (OR, 2.66),
particularly among those with prior exposure to known GSTP1 substrates
(OR, 4.34), than in patients with de novo AML, and not among those t-AML
patients with prior exposure to radiotherapy alone (OR, 1.01). These
data suggested that inheritance of at least 1 GSTP1 valine-105 allele
confers a significantly increased risk of developing t-AML after
cytotoxic chemotherapy, but not after radiotherapy.
Beutler et al. (1988) found unexplained red cell GST deficiency in an
otherwise healthy adult male with mild hemolytic anemia accompanied by
splenomegaly, indirect hyperbilirubinemia, and cholelithiasis. Residual
enzyme activity was only about 15% of mean normal. Because he was
adopted and childless, the hereditary nature of the defect could not be
established. Modest decreases in leukocyte and platelet GST activities
were documented.
Menegon et al. (1998) pursued the hypotheses that Parkinson disease
(168600) is secondary to the presence of neurotoxins and that pesticides
are possible causative agents. Because glutathione transferases
metabolize xenobiotics, including pesticides, they investigated the role
of GST polymorphisms in the pathogenesis of idiopathic Parkinson
disease. In 95 Parkinson disease patients and 95 controls, they
genotyped PCR polymorphisms in 4 GST classes: GST1, GSTT1 (600436),
GSTP1, and GSTZ1 (603758). Associations were found only with the GSTP1
polymorphisms. Analyzing the genotypes of those subjects who reported
exposure to pesticides (39 patients and 26 controls), they found that
the distribution of genotypes of the GSTP1 polymorphisms differed
significantly between patients and controls. These differences seemed to
be secondary to an excess of heterozygotes and noncarriers of A alleles
among patients. Menegon et al. (1998) interpreted these results as
suggesting that GSTP1, which is expressed in the blood-brain barrier,
may influence response to neurotoxins and explain the susceptibility of
some people to the parkinsonism-inducing effects of pesticides. In a
commentary entitled 'Parkinson's Disease: Nature Meets Nurture,' Golbe
(1998) pointed out that virtually every case-control study investigating
the risk of Parkinson disease has shown that pesticide or herbicide
exposure, or rural or farm experiences, increases Parkinson disease
risk, typically 3-fold or 4-fold. Furthermore, rotenone, a commonly used
pesticide, shares with the active metabolite of MPTP (a known cause of
parkinsonism in humans and laboratory animals) the same neurotoxic
action, namely inhibition of complex I, part of the mitochondrial
respiratory enzyme chain.
Wilk et al. (2006) presented evidence suggesting that exposure to
herbicides may be an effect modifier of the relationship between GSTP1
polymorphisms and age of onset in Parkinson disease.
Zusterzeel et al. (1999) found that GSTP1 is the main GST isoform in
normal placental and decidual tissue. In preeclamptic (189800) women,
they found lower median placental and decidual GSTP1 levels compared to
those in controls. Zusterzeel et al. (1999) suggested that reduced
levels of GSTP1 in preeclampsia may indicate a decreased capacity of the
detoxification system, resulting in a higher susceptibility to
preeclampsia. Among 113 preeclampsia trios (mother, father, and baby),
Zusterzeel et al. (2002) found an increased frequency of the GSTP1
val105 polymorphism (see 134660.0002) in mothers, fathers, and offspring
of preeclamptic pregnancies compared to controls. There was no
significant difference in the GSTP1 allele frequencies in preeclamptic
mothers, fathers, and offspring. The authors emphasized the paternal
contribution to the risk for preeclampsia.
Gilliland et al. (2004) found that GSTP1 and GSTM1 modify the adjuvant
effect of diesel exhaust particles on allergic inflammation. They
challenged ragweed-sensitive patients intranasally with allergen alone
and with allergen plus diesel exhaust particles and found that
individuals with GSTM1 null or GSTP1 ile105 wildtype genotypes showed
significant increases in IgE and histamine after challenge with diesel
exhaust particles and allergens; the increase was largest in patients
with both the GSTP1 ile/ile and GSTM1 null genotypes.
See 606581 for discussion of a possible association between variation in
GSTP1 gene and susceptibility to polysubstance abuse.
*FIELD* AV
.0001
GLUTATHIONE S-TRANSFERASE PI POLYMORPHISM, TYPE A
GSTP1, ILE105 AND ALA114
Ali-Osman et al. (1997) identified 3 polymorphic forms of the GSTP1
gene. One allele, GSTP1*A, has ATC (ile) as codon 105 and GCG (ala) as
codon 114. (Ali-Osman et al. (1997) had designated the substitutions
ILE104 and ALA113 based on then-current numbering.)
.0002
GLUTATHIONE S-TRANSFERASE PI POLYMORPHISM, TYPE B
GSTP1, VAL105 AND ALA114
Ali-Osman et al. (1997) identified 3 polymorphic forms of the GSTP1
gene. One allele, GSTP1*B, has GTC (val) as codon 105 and GCG (ala) as
codon 114. (Ali-Osman et al. (1997) had designated the substitutions
VAL104 and ALA113 based on then-current numbering.)
.0003
GLUTATHIONE S-TRANSFERASE PI POLYMORPHISM, TYPE C
GSTP1, VAL105 AND VAL114
Ali-Osman et al. (1997) identified 3 polymorphic forms of the GSTP1
gene. One allele, GSTP1*C, has GTC (val) as codon 105 and GTG (val) as
codon 114. (Ali-Osman et al. (1997) had designated the substitutions
VAL104 and VAL113 based on then-current numbering.)
*FIELD* SA
Awasthi et al. (1981)
*FIELD* RF
1. Ali-Osman, F.; Akande, O.; Antoun, G.; Mao, J.-X.; Buolamwini,
J.: Molecular cloning, characterization, and expression in Escherichia
coli of full-length cDNAs of three human glutathione S-transferase
Pi gene variants: evidence for differential catalytic activity of
the encoded proteins. J. Biol. Chem. 272: 10004-10012, 1997.
2. Allan, J. M.; Wild, C. P.; Rollinson, S.; Willett, E. V.; Moorman,
A. V.; Dovey, G. J.; Roddam, P. L.; Roman, E.; Cartwright, R. A.;
Morgan, G. J.: Polymorphism in glutathione S-transferase P1 is associated
with susceptibility to chemotherapy-induced leukemia. Proc. Nat.
Acad. Sci. 98: 11592-11597, 2001. Note: Erratum: Proc. Nat. Acad.
Sci. 98: 15394 only, 2001.
3. Awasthi, Y. C.; Dao, D. D.; Partridge, C. A.: Genetic origin of
human glutathione S-transferases. (Abstract) Am. J. Hum. Genet. 33:
35, 1981.
4. Beutler, E.; Dunning, D.; Dabe, I. B.; Forman, L.: Erythrocyte
glutathione S-transferase deficiency and hemolytic anemia. Blood 72:
73-77, 1988.
5. Board, P.; Smith, S.; Green, J.; Coggan, M.; Suzuki, T.: Evidence
against a relationship between fatty acid ethyl ester synthase and
the pi class glutatione S-transferase in humans. J. Biol. Chem. 268:
15655-15658, 1993.
6. Board, P. G.: Biochemical genetics of glutathione-S-transferase
in man. Am. J. Hum. Genet. 33: 36-43, 1981.
7. Board, P. G.; Coggan, M.; Woodcock, D. M.: The human Pi class
glutathione transferase sequence at 12q13-q14 is a reverse-transcribed
pseudogene. Genomics 14: 470-473, 1992.
8. Board, P. G.; Webb, G. C.; Coggan, M.: Isolation of a cDNA clone
and localization of the human glutathione S-transferase 3 genes to
chromosome bands 11q13 and 12q13-14. Ann. Hum. Genet. 53: 205-213,
1989.
9. Bora, P. S.; Bora, N. S.; Wu, X.; Lange, L. G.: Molecular cloning,
sequencing, and expression of human myocardial fatty acid ethyl ester
synthase-III cDNA. J. Biol. Chem. 266: 16774-16777, 1991.
10. Gilliland, F. D.; Li, Y.-F.; Saxon, A.; Diaz-Sanchez, D.: Effect
of glutathione-S-transferase M1 and P1 genotypes on xenobiotic enhancement
of allergic responses: randomised, placebo-controlled crossover study. Lancet 363:
119-125, 2004.
11. Golbe, L. I.: Parkinson's disease: nature meets nurture. Lancet 352:
1328-1329, 1998.
12. Henderson, C. J.; Wolf, C. R.; Kitteringham, N.; Powell, H.; Otto,
D.; Park, B. K.: Increased resistance to acetaminophen hepatotoxicity
in mice lacking glutathione S-transferase Pi. Proc. Nat. Acad. Sci. 97:
12741-12745, 2000.
13. Islam, M. Q.; Platz, A.; Szpirer, J.; Szpirer, C.; Levan, G.;
Mannervik, B.: Chromosomal localization of human glutathione transferase
genes of classes alpha, mu and pi. Hum. Genet. 82: 338-342, 1989.
14. Kano, T.; Sakai, M.; Muramatsu, M.: Structure and expression
of a human class pi glutathione S-transferase messenger RNA. Cancer
Res. 47: 5626-5630, 1987.
15. Kingsley, D. M.; Jenkins, N. A.; Copeland, N. G.: A molecular
genetic linkage map of mouse chromosome 9 with regional localizations
for the Gsta, T3g, Ets-1 and Ldlr loci. Genetics 123: 165-172, 1989.
16. Konohana, A.; Konohana, I.; Schroeder, W. T.; O'Brien, W. R.;
Amagai, M.; Greer, J.; Shimizu, N.; Gammon, W. R.; Siciliano, M. J.;
Duvic, M.: Placental glutathione-S-transferase-pi mRNA is abundantly
expressed in human skin. J. Invest. Derm. 95: 119-126, 1990.
17. Laisney, V.; Van Cong, N.; Gross, M.-S.; Parisi, I.; Foubert,
C.; Weil, D.; Frezal, J.: Localisation du groupe syntenique LDHA-GST3-ESA4
sur le chromosome 11 chez l'homme: analyses des hybrides homme-rongeur
classiques et d'un type nouveau (non adherents a la paroi). Ann.
Genet. 26: 69-74, 1983.
18. Laisney, V.; Van Cong, N.; Gross, M. S.; Frezal, J.: Human genes
for glutathione S-transferases. Hum. Genet. 68: 221-227, 1984.
19. Menegon, A.; Board, P. G.; Blackburn, A. C.; Mellick, G. D.; Le
Couteur, D. G.: Parkinson's disease, pesticides, and glutathione
transferase polymorphisms. Lancet 352: 1344-1346, 1998.
20. Morrow, C. S.; Cowan, K. H.; Goldsmith, M. E.: Structure of the
human genomic glutathione S-transferase-pi gene. Gene 75: 3-11,
1989.
21. Moscow, J. A.; Fairchild, C. R.; Madden, M. J.; Ransom, D. T.;
Wieand, H. S.; O'Brien, E. E.; Poplack, D. G.; Cossman, J.; Myers,
C. E.; Cowan, K. H.: Expression of anionic glutathione-S-transferase
and P-glycoprotein genes in human tissues and tumors. Cancer Res. 49:
1422-1428, 1989.
22. Moscow, J. A.; Townsend, A. J.; Goldsmith, M. E.; Whang-Peng,
J.; Vickers, P. J.; Poisson, R.; Legault-Poisson, S.; Myers, C. E.;
Cowan, K. H.: Isolation of the human anionic glutathione S-transferase
cDNA and the relation of its gene expression to estrogen-receptor
content in primary breast cancer. Proc. Nat. Acad. Sci. 85: 6518-6522,
1988.
23. Rochelle, J. M.; Watson, M. L.; Oakey, R. J.; Seldin, M. F.:
A linkage map of mouse chromosome 19: definition of comparative mapping
relationships with human chromosomes 10 and 11 including the MEN1
locus. Genomics 14: 26-31, 1992.
24. Seldin, M. F.; Saunders, A. M.; Rochelle, J. M.; Howard, T. A.
: A proximal mouse chromosome 9 linkage map that further defines linkage
groups homologous with segments of human chromosomes 11, 15, and 19. Genomics 9:
678-685, 1991.
25. Silberstein, D. L.; Sakaguchi, A. Y.; Shows, T. B.: Assignment
of the gene for glutathione S-transferase-1 (GST1) to human chromosome
11. (Abstract) Cytogenet. Cell Genet. 32: 317, 1982.
26. Silberstein, D. L.; Shows, T. B.: Gene for glutathione S-transferase-1
(GST1) is on human chromosome 11. Somat. Cell Genet. 8: 667-675,
1982.
27. Smith, C. M.; Bora, P. S.; Bora, N. S.; Jones, C.; Gerhard, D.
S.: Genetic and radiation-reduced somatic cell hybrid sublocalization
of the human GSTP1 gene. Cytogenet. Cell Genet. 71: 235-239, 1995.
28. Suzuki, T.; Board, P.: Glutathione-S-transferase gene mapped
to chromosome 11 is GST3 not GST1. (Letter) Somat. Cell Molec. Genet. 10:
319-320, 1984.
29. Wilk, J. B.; Tobin, J. E.; Suchowersky, O.; Shill, H. A.; Klein,
C.; Wooten, G. F.; Lew, M. F.; Mark, M. H.; Guttman, M.; Watts, R.
L.; Singer, C.; Growdon, J. H.; and 26 others: Herbicide exposure
modifies GSTP1 haplotype association to Parkinson onset age: the GenePD
study. Neurology 67: 2206-2210, 2006.
30. Zusterzeel, P. L. M.; Peters, W. H. M.; de Bruyn, M. A. H.; Knapen,
M. F. C. M.; Merkus, H. M. W. M.; Steegers, E. A. P.: Glutathione
S-transferase isoenzymes in decidua and placenta of preeclamptic pregnancies. Obstet.
Gynec. 94: 1033-1038, 1999.
31. Zusterzeel, P. L. M.; te Morsche, R.; Raijmakers, M. T. M.; Roes,
E. M.; Peters, W. H. M.; Steegers, E. A. P.: Paternal contribution
to the risk for pre-eclampsia. J. Med. Genet. 39: 44-45, 2002.
*FIELD* CN
Cassandra L. Kniffin - updated: 12/26/2007
John Logan Black, III - updated: 8/9/2005
Marla J. F. O'Neill - updated: 2/5/2004
Cassandra L. Kniffin - reorganized: 10/19/2003
Cassandra L. Kniffin - updated: 10/17/2003
Victor A. McKusick - updated: 11/1/2001
Victor A. McKusick - updated: 11/30/2000
Victor A. McKusick - updated: 2/3/1999
Rebekah S. Rasooly - updated: 10/7/1998
*FIELD* CD
Victor A. McKusick: 11/15/1991
*FIELD* ED
carol: 11/14/2013
terry: 7/27/2012
carol: 5/25/2012
carol: 9/18/2008
wwang: 1/15/2008
ckniffin: 12/26/2007
carol: 1/10/2006
carol: 12/6/2005
terry: 8/9/2005
carol: 3/9/2004
carol: 2/5/2004
carol: 10/19/2003
ckniffin: 10/17/2003
carol: 11/20/2001
mcapotos: 11/20/2001
mcapotos: 11/16/2001
terry: 11/1/2001
mcapotos: 12/12/2000
mcapotos: 12/6/2000
terry: 11/30/2000
alopez: 4/21/1999
carol: 4/14/1999
terry: 2/9/1999
terry: 2/8/1999
terry: 2/3/1999
alopez: 10/8/1998
alopez: 10/7/1998
supermim: 3/16/1992
carol: 11/15/1991