Full text data of GSTT1
GSTT1
[Confidence: low (only semi-automatic identification from reviews)]
Glutathione S-transferase theta-1; 2.5.1.18 (GST class-theta-1; Glutathione transferase T1-1)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
Glutathione S-transferase theta-1; 2.5.1.18 (GST class-theta-1; Glutathione transferase T1-1)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
UniProt
P30711
ID GSTT1_HUMAN Reviewed; 240 AA.
AC P30711; O00226; Q5TZY2; Q969K8; Q96IY3;
DT 01-APR-1993, integrated into UniProtKB/Swiss-Prot.
read moreDT 23-JAN-2007, sequence version 4.
DT 22-JAN-2014, entry version 153.
DE RecName: Full=Glutathione S-transferase theta-1;
DE EC=2.5.1.18;
DE AltName: Full=GST class-theta-1;
DE AltName: Full=Glutathione transferase T1-1;
GN Name=GSTT1;
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=8198545;
RA Pemble S., Schroeder K.R., Spencer S.R., Meyer D.J., Hallier E.,
RA Bolt H.M., Ketterer B., Taylor J.B.;
RT "Human glutathione S-transferase theta (GSTT1): cDNA cloning and the
RT characterization of a genetic polymorphism.";
RL Biochem. J. 300:271-276(1994).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA], AND CHARACTERIZATION.
RX PubMed=9434735; DOI=10.1006/abbi.1997.0357;
RA Jemth P., Mannervik B.;
RT "Kinetic characterization of recombinant human glutathione transferase
RT T1-1, a polymorphic detoxication enzyme.";
RL Arch. Biochem. Biophys. 348:247-254(1997).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=10975610; DOI=10.1097/00008571-200008000-00009;
RA Sprenger R., Schlagenhaufer R., Kerb R., Bruhn C., Brockmoeller J.,
RA Roots I., Brinkmann U.;
RT "Characterization of the glutathione S-transferase GSTT1 deletion:
RT discrimination of all genotypes by polymerase chain reaction indicates
RT a trimodular genotype-phenotype correlation.";
RL Pharmacogenetics 10:557-565(2000).
RN [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC TISSUE=Thymus;
RA Iida A., Kondo K., Kitamura Y., Mishima C., Osawa S., Kitamoto T.,
RA Harigae C., Nakamura Y.;
RT "Complete genomic structure of human glutathione S-transferase TT1.";
RL Submitted (MAR-2001) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT ILE-169.
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 [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=10591208; DOI=10.1038/990031;
RA Dunham I., Hunt A.R., Collins J.E., Bruskiewich R., Beare D.M.,
RA Clamp M., Smink L.J., Ainscough R., Almeida J.P., Babbage A.K.,
RA Bagguley C., Bailey J., Barlow K.F., Bates K.N., Beasley O.P.,
RA Bird C.P., Blakey S.E., Bridgeman A.M., Buck D., Burgess J.,
RA Burrill W.D., Burton J., Carder C., Carter N.P., Chen Y., Clark G.,
RA Clegg S.M., Cobley V.E., Cole C.G., Collier R.E., Connor R.,
RA Conroy D., Corby N.R., Coville G.J., Cox A.V., Davis J., Dawson E.,
RA Dhami P.D., Dockree C., Dodsworth S.J., Durbin R.M., Ellington A.G.,
RA Evans K.L., Fey J.M., Fleming K., French L., Garner A.A.,
RA Gilbert J.G.R., Goward M.E., Grafham D.V., Griffiths M.N.D., Hall C.,
RA Hall R.E., Hall-Tamlyn G., Heathcott R.W., Ho S., Holmes S.,
RA Hunt S.E., Jones M.C., Kershaw J., Kimberley A.M., King A.,
RA Laird G.K., Langford C.F., Leversha M.A., Lloyd C., Lloyd D.M.,
RA Martyn I.D., Mashreghi-Mohammadi M., Matthews L.H., Mccann O.T.,
RA Mcclay J., Mclaren S., McMurray A.A., Milne S.A., Mortimore B.J.,
RA Odell C.N., Pavitt R., Pearce A.V., Pearson D., Phillimore B.J.C.T.,
RA Phillips S.H., Plumb R.W., Ramsay H., Ramsey Y., Rogers L., Ross M.T.,
RA Scott C.E., Sehra H.K., Skuce C.D., Smalley S., Smith M.L.,
RA Soderlund C., Spragon L., Steward C.A., Sulston J.E., Swann R.M.,
RA Vaudin M., Wall M., Wallis J.M., Whiteley M.N., Willey D.L.,
RA Williams L., Williams S.A., Williamson H., Wilmer T.E., Wilming L.,
RA Wright C.L., Hubbard T., Bentley D.R., Beck S., Rogers J., Shimizu N.,
RA Minoshima S., Kawasaki K., Sasaki T., Asakawa S., Kudoh J.,
RA Shintani A., Shibuya K., Yoshizaki Y., Aoki N., Mitsuyama S.,
RA Roe B.A., Chen F., Chu L., Crabtree J., Deschamps S., Do A., Do T.,
RA Dorman A., Fang F., Fu Y., Hu P., Hua A., Kenton S., Lai H., Lao H.I.,
RA Lewis J., Lewis S., Lin S.-P., Loh P., Malaj E., Nguyen T., Pan H.,
RA Phan S., Qi S., Qian Y., Ray L., Ren Q., Shaull S., Sloan D., Song L.,
RA Wang Q., Wang Y., Wang Z., White J., Willingham D., Wu H., Yao Z.,
RA Zhan M., Zhang G., Chissoe S., Murray J., Miller N., Minx P.,
RA Fulton R., Johnson D., Bemis G., Bentley D., Bradshaw H., Bourne S.,
RA Cordes M., Du Z., Fulton L., Goela D., Graves T., Hawkins J.,
RA Hinds K., Kemp K., Latreille P., Layman D., Ozersky P., Rohlfing T.,
RA Scheet P., Walker C., Wamsley A., Wohldmann P., Pepin K., Nelson J.,
RA Korf I., Bedell J.A., Hillier L.W., Mardis E., Waterston R.,
RA Wilson R., Emanuel B.S., Shaikh T., Kurahashi H., Saitta S.,
RA Budarf M.L., McDermid H.E., Johnson A., Wong A.C.C., Morrow B.E.,
RA Edelmann L., Kim U.J., Shizuya H., Simon M.I., Dumanski J.P.,
RA Peyrard M., Kedra D., Seroussi E., Fransson I., Tapia I., Bruder C.E.,
RA O'Brien K.P., Wilkinson P., Bodenteich A., Hartman K., Hu X.,
RA Khan A.S., Lane L., Tilahun Y., Wright H.;
RT "The DNA sequence of human chromosome 22.";
RL Nature 402:489-495(1999).
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
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 [8]
RP PROTEIN SEQUENCE OF 2-47.
RC TISSUE=Liver;
RX PubMed=1848757;
RA Meyer D.J., Coles B., Pemble S.E., Gilmore K.S., Fraser G.M.,
RA Ketterer B.;
RT "Theta, a new class of glutathione transferases purified from rat and
RT man.";
RL Biochem. J. 274:409-414(1991).
RN [9]
RP TISSUE SPECIFICITY.
RC TISSUE=Liver, and Lung;
RX PubMed=8761485;
RA Mainwaring G.W., Williams S.M., Foster J.R., Tugwood J., Green T.;
RT "The distribution of theta-class glutathione S-transferases in the
RT liver and lung of mouse, rat and human.";
RL Biochem. J. 318:297-303(1996).
RN [10]
RP FUNCTION, AND CATALYTIC ACTIVITY.
RX PubMed=20097269; DOI=10.1016/j.bbagen.2010.01.003;
RA Shokeer A., Mannervik B.;
RT "Residue 234 is a master switch of the alternative-substrate activity
RT profile of human and rodent theta class glutathione transferase T1-
RT 1.";
RL Biochim. Biophys. Acta 1800:466-473(2010).
RN [11]
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 [12]
RP X-RAY CRYSTALLOGRAPHY (1.5 ANGSTROMS) OF WILD-TYPE AND MUTANT ARG-234
RP IN COMPLEX WITH HEXYLGLUTATHIONE, CATALYTIC ACTIVITY, FUNCTION,
RP SUBUNIT, AND MUTAGENESIS OF HIS-176 AND TRP-234.
RX PubMed=16298388; DOI=10.1016/j.jmb.2005.10.049;
RA Tars K., Larsson A.K., Shokeer A., Olin B., Mannervik B.,
RA Kleywegt G.J.;
RT "Structural basis of the suppressed catalytic activity of wild-type
RT human glutathione transferase T1-1 compared to its W234R mutant.";
RL J. Mol. Biol. 355:96-105(2006).
CC -!- FUNCTION: Conjugation of reduced glutathione to a wide number of
CC exogenous and endogenous hydrophobic electrophiles. Acts on 1,2-
CC epoxy-3-(4-nitrophenoxy)propane, phenethylisothiocyanate 4-
CC nitrobenzyl chloride and 4-nitrophenethyl bromide. Displays
CC glutathione peroxidase activity with cumene hydroperoxide.
CC -!- CATALYTIC ACTIVITY: RX + glutathione = HX + R-S-glutathione.
CC -!- SUBUNIT: Homodimer.
CC -!- SUBCELLULAR LOCATION: Cytoplasm.
CC -!- TISSUE SPECIFICITY: Found in erythrocyte. Expressed at low levels
CC in liver. In lung, expressed at low levels in Clara cells and
CC ciliated cells at the alveolar/bronchiolar junction. Absent from
CC epithelial cells of larger bronchioles.
CC -!- POLYMORPHISM: The GSTT1 gene is absent from 38% of the population.
CC The presence or absence of the GSTT1 gene is coincident with the
CC conjugator (GSST1+) and non-conjugator (GSTT1-) phenotypes
CC respectively. The GSTT1+ phenotype can catalyze the glutathione
CC conjugation of dichloromethane.
CC -!- SIMILARITY: Belongs to the GST superfamily. Theta family.
CC -!- SIMILARITY: Contains 1 GST C-terminal domain.
CC -!- SIMILARITY: Contains 1 GST N-terminal domain.
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;=GSTT1";
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DR EMBL; X79389; CAA55935.1; -; mRNA.
DR EMBL; AF435971; AAL31549.1; -; mRNA.
DR EMBL; AF240786; AAG02374.1; -; Genomic_DNA.
DR EMBL; AB057594; BAB39498.1; -; Genomic_DNA.
DR EMBL; BT019951; AAV38754.1; -; mRNA.
DR EMBL; Z84718; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC007065; AAH07065.1; -; mRNA.
DR PIR; S44358; S44358.
DR RefSeq; NP_000844.2; NM_000853.2.
DR UniGene; Hs.268573; -.
DR UniGene; Hs.738514; -.
DR PDB; 2C3N; X-ray; 1.50 A; A/B/C/D=2-239.
DR PDB; 2C3Q; X-ray; 1.85 A; A/B/C/D=2-239.
DR PDB; 2C3T; X-ray; 2.40 A; A/B/C/D=2-239.
DR PDBsum; 2C3N; -.
DR PDBsum; 2C3Q; -.
DR PDBsum; 2C3T; -.
DR ProteinModelPortal; P30711; -.
DR SMR; P30711; 2-240.
DR IntAct; P30711; 1.
DR STRING; 9606.ENSP00000248935; -.
DR ChEMBL; CHEMBL2141; -.
DR DrugBank; DB00143; Glutathione.
DR PhosphoSite; P30711; -.
DR DMDM; 21264427; -.
DR PaxDb; P30711; -.
DR PRIDE; P30711; -.
DR DNASU; 2952; -.
DR Ensembl; ENST00000248935; ENSP00000248935; ENSG00000184674.
DR GeneID; 2952; -.
DR KEGG; hsa:2952; -.
DR UCSC; uc002zze.4; human.
DR CTD; 2952; -.
DR GeneCards; GC22M024952; -.
DR H-InvDB; HIX0019638; -.
DR HGNC; HGNC:4641; GSTT1.
DR MIM; 600436; gene.
DR neXtProt; NX_P30711; -.
DR PharmGKB; PA183; -.
DR eggNOG; COG0625; -.
DR HOGENOM; HOG000125747; -.
DR HOVERGEN; HBG051854; -.
DR InParanoid; P30711; -.
DR KO; K00799; -.
DR OMA; TVKQKLM; -.
DR PhylomeDB; P30711; -.
DR Reactome; REACT_111217; Metabolism.
DR SABIO-RK; P30711; -.
DR EvolutionaryTrace; P30711; -.
DR GeneWiki; GSTT1; -.
DR GenomeRNAi; 2952; -.
DR NextBio; 11698; -.
DR PRO; PR:P30711; -.
DR ArrayExpress; P30711; -.
DR Bgee; P30711; -.
DR CleanEx; HS_GSTT1; -.
DR Genevestigator; P30711; -.
DR GO; GO:0005829; C:cytosol; IDA:UniProtKB.
DR GO; GO:0004602; F:glutathione peroxidase activity; IDA:UniProtKB.
DR GO; GO:0004364; F:glutathione transferase activity; IDA:UniProtKB.
DR GO; GO:1901687; P:glutathione derivative biosynthetic process; TAS:Reactome.
DR GO; GO:0006749; P:glutathione metabolic process; IDA:UniProtKB.
DR GO; GO:0042493; P:response to drug; IEA:Ensembl.
DR GO; GO:0014070; P:response to organic cyclic compound; IEA:Ensembl.
DR GO; GO:0006805; P:xenobiotic metabolic process; TAS:Reactome.
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; IPR012336; Thioredoxin-like_fold.
DR Pfam; PF00043; GST_C; 1.
DR Pfam; PF02798; GST_N; 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; Complete proteome; Cytoplasm; Direct protein sequencing;
KW Polymorphism; Reference proteome; Transferase.
FT INIT_MET 1 1 Removed.
FT CHAIN 2 240 Glutathione S-transferase theta-1.
FT /FTId=PRO_0000185938.
FT DOMAIN 2 82 GST N-terminal.
FT DOMAIN 88 220 GST C-terminal.
FT REGION 53 54 Glutathione binding.
FT REGION 66 67 Glutathione binding.
FT BINDING 40 40 Glutathione.
FT VARIANT 21 21 A -> T (in dbSNP:rs2266635).
FT /FTId=VAR_014501.
FT VARIANT 141 141 D -> N (in dbSNP:rs2266633).
FT /FTId=VAR_014502.
FT VARIANT 169 169 V -> I (in dbSNP:rs2266637).
FT /FTId=VAR_014503.
FT VARIANT 173 173 E -> K (in dbSNP:rs2234953).
FT /FTId=VAR_014504.
FT MUTAGEN 176 176 H->Q: Increases activity towards
FT alkylhalogenides, but not hydroperoxides.
FT MUTAGEN 234 234 W->R: Facilitates binding of substrates
FT and increases catalytic activity.
FT CONFLICT 43 44 DA -> SD (in Ref. 8; AA sequence).
FT CONFLICT 45 45 F -> C (in Ref. 7; AAH07065).
FT CONFLICT 126 126 E -> G (in Ref. 1; CAA55935).
FT STRAND 3 7
FT HELIX 12 23
FT STRAND 29 32
FT HELIX 35 37
FT HELIX 39 41
FT HELIX 43 48
FT STRAND 56 59
FT STRAND 62 65
FT HELIX 67 77
FT HELIX 82 84
FT HELIX 89 101
FT HELIX 102 104
FT HELIX 106 117
FT HELIX 118 123
FT HELIX 130 150
FT TURN 151 154
FT STRAND 155 162
FT HELIX 165 179
FT HELIX 189 202
FT HELIX 204 210
FT HELIX 212 215
FT HELIX 216 219
FT HELIX 225 239
SQ SEQUENCE 240 AA; 27335 MW; BD19F2BFDEF9F619 CRC64;
MGLELYLDLL SQPCRAVYIF AKKNDIPFEL RIVDLIKGQH LSDAFAQVNP LKKVPALKDG
DFTLTESVAI LLYLTRKYKV PDYWYPQDLQ ARARVDEYLA WQHTTLRRSC LRALWHKVMF
PVFLGEPVSP QTLAATLAEL DVTLQLLEDK FLQNKAFLTG PHISLADLVA ITELMHPVGA
GCQVFEGRPK LATWRQRVEA AVGEDLFQEA HEVILKAKDF PPADPTIKQK LMPWVLAMIR
//
ID GSTT1_HUMAN Reviewed; 240 AA.
AC P30711; O00226; Q5TZY2; Q969K8; Q96IY3;
DT 01-APR-1993, integrated into UniProtKB/Swiss-Prot.
read moreDT 23-JAN-2007, sequence version 4.
DT 22-JAN-2014, entry version 153.
DE RecName: Full=Glutathione S-transferase theta-1;
DE EC=2.5.1.18;
DE AltName: Full=GST class-theta-1;
DE AltName: Full=Glutathione transferase T1-1;
GN Name=GSTT1;
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=8198545;
RA Pemble S., Schroeder K.R., Spencer S.R., Meyer D.J., Hallier E.,
RA Bolt H.M., Ketterer B., Taylor J.B.;
RT "Human glutathione S-transferase theta (GSTT1): cDNA cloning and the
RT characterization of a genetic polymorphism.";
RL Biochem. J. 300:271-276(1994).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA], AND CHARACTERIZATION.
RX PubMed=9434735; DOI=10.1006/abbi.1997.0357;
RA Jemth P., Mannervik B.;
RT "Kinetic characterization of recombinant human glutathione transferase
RT T1-1, a polymorphic detoxication enzyme.";
RL Arch. Biochem. Biophys. 348:247-254(1997).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=10975610; DOI=10.1097/00008571-200008000-00009;
RA Sprenger R., Schlagenhaufer R., Kerb R., Bruhn C., Brockmoeller J.,
RA Roots I., Brinkmann U.;
RT "Characterization of the glutathione S-transferase GSTT1 deletion:
RT discrimination of all genotypes by polymerase chain reaction indicates
RT a trimodular genotype-phenotype correlation.";
RL Pharmacogenetics 10:557-565(2000).
RN [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC TISSUE=Thymus;
RA Iida A., Kondo K., Kitamura Y., Mishima C., Osawa S., Kitamoto T.,
RA Harigae C., Nakamura Y.;
RT "Complete genomic structure of human glutathione S-transferase TT1.";
RL Submitted (MAR-2001) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT ILE-169.
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 [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=10591208; DOI=10.1038/990031;
RA Dunham I., Hunt A.R., Collins J.E., Bruskiewich R., Beare D.M.,
RA Clamp M., Smink L.J., Ainscough R., Almeida J.P., Babbage A.K.,
RA Bagguley C., Bailey J., Barlow K.F., Bates K.N., Beasley O.P.,
RA Bird C.P., Blakey S.E., Bridgeman A.M., Buck D., Burgess J.,
RA Burrill W.D., Burton J., Carder C., Carter N.P., Chen Y., Clark G.,
RA Clegg S.M., Cobley V.E., Cole C.G., Collier R.E., Connor R.,
RA Conroy D., Corby N.R., Coville G.J., Cox A.V., Davis J., Dawson E.,
RA Dhami P.D., Dockree C., Dodsworth S.J., Durbin R.M., Ellington A.G.,
RA Evans K.L., Fey J.M., Fleming K., French L., Garner A.A.,
RA Gilbert J.G.R., Goward M.E., Grafham D.V., Griffiths M.N.D., Hall C.,
RA Hall R.E., Hall-Tamlyn G., Heathcott R.W., Ho S., Holmes S.,
RA Hunt S.E., Jones M.C., Kershaw J., Kimberley A.M., King A.,
RA Laird G.K., Langford C.F., Leversha M.A., Lloyd C., Lloyd D.M.,
RA Martyn I.D., Mashreghi-Mohammadi M., Matthews L.H., Mccann O.T.,
RA Mcclay J., Mclaren S., McMurray A.A., Milne S.A., Mortimore B.J.,
RA Odell C.N., Pavitt R., Pearce A.V., Pearson D., Phillimore B.J.C.T.,
RA Phillips S.H., Plumb R.W., Ramsay H., Ramsey Y., Rogers L., Ross M.T.,
RA Scott C.E., Sehra H.K., Skuce C.D., Smalley S., Smith M.L.,
RA Soderlund C., Spragon L., Steward C.A., Sulston J.E., Swann R.M.,
RA Vaudin M., Wall M., Wallis J.M., Whiteley M.N., Willey D.L.,
RA Williams L., Williams S.A., Williamson H., Wilmer T.E., Wilming L.,
RA Wright C.L., Hubbard T., Bentley D.R., Beck S., Rogers J., Shimizu N.,
RA Minoshima S., Kawasaki K., Sasaki T., Asakawa S., Kudoh J.,
RA Shintani A., Shibuya K., Yoshizaki Y., Aoki N., Mitsuyama S.,
RA Roe B.A., Chen F., Chu L., Crabtree J., Deschamps S., Do A., Do T.,
RA Dorman A., Fang F., Fu Y., Hu P., Hua A., Kenton S., Lai H., Lao H.I.,
RA Lewis J., Lewis S., Lin S.-P., Loh P., Malaj E., Nguyen T., Pan H.,
RA Phan S., Qi S., Qian Y., Ray L., Ren Q., Shaull S., Sloan D., Song L.,
RA Wang Q., Wang Y., Wang Z., White J., Willingham D., Wu H., Yao Z.,
RA Zhan M., Zhang G., Chissoe S., Murray J., Miller N., Minx P.,
RA Fulton R., Johnson D., Bemis G., Bentley D., Bradshaw H., Bourne S.,
RA Cordes M., Du Z., Fulton L., Goela D., Graves T., Hawkins J.,
RA Hinds K., Kemp K., Latreille P., Layman D., Ozersky P., Rohlfing T.,
RA Scheet P., Walker C., Wamsley A., Wohldmann P., Pepin K., Nelson J.,
RA Korf I., Bedell J.A., Hillier L.W., Mardis E., Waterston R.,
RA Wilson R., Emanuel B.S., Shaikh T., Kurahashi H., Saitta S.,
RA Budarf M.L., McDermid H.E., Johnson A., Wong A.C.C., Morrow B.E.,
RA Edelmann L., Kim U.J., Shizuya H., Simon M.I., Dumanski J.P.,
RA Peyrard M., Kedra D., Seroussi E., Fransson I., Tapia I., Bruder C.E.,
RA O'Brien K.P., Wilkinson P., Bodenteich A., Hartman K., Hu X.,
RA Khan A.S., Lane L., Tilahun Y., Wright H.;
RT "The DNA sequence of human chromosome 22.";
RL Nature 402:489-495(1999).
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
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 [8]
RP PROTEIN SEQUENCE OF 2-47.
RC TISSUE=Liver;
RX PubMed=1848757;
RA Meyer D.J., Coles B., Pemble S.E., Gilmore K.S., Fraser G.M.,
RA Ketterer B.;
RT "Theta, a new class of glutathione transferases purified from rat and
RT man.";
RL Biochem. J. 274:409-414(1991).
RN [9]
RP TISSUE SPECIFICITY.
RC TISSUE=Liver, and Lung;
RX PubMed=8761485;
RA Mainwaring G.W., Williams S.M., Foster J.R., Tugwood J., Green T.;
RT "The distribution of theta-class glutathione S-transferases in the
RT liver and lung of mouse, rat and human.";
RL Biochem. J. 318:297-303(1996).
RN [10]
RP FUNCTION, AND CATALYTIC ACTIVITY.
RX PubMed=20097269; DOI=10.1016/j.bbagen.2010.01.003;
RA Shokeer A., Mannervik B.;
RT "Residue 234 is a master switch of the alternative-substrate activity
RT profile of human and rodent theta class glutathione transferase T1-
RT 1.";
RL Biochim. Biophys. Acta 1800:466-473(2010).
RN [11]
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 [12]
RP X-RAY CRYSTALLOGRAPHY (1.5 ANGSTROMS) OF WILD-TYPE AND MUTANT ARG-234
RP IN COMPLEX WITH HEXYLGLUTATHIONE, CATALYTIC ACTIVITY, FUNCTION,
RP SUBUNIT, AND MUTAGENESIS OF HIS-176 AND TRP-234.
RX PubMed=16298388; DOI=10.1016/j.jmb.2005.10.049;
RA Tars K., Larsson A.K., Shokeer A., Olin B., Mannervik B.,
RA Kleywegt G.J.;
RT "Structural basis of the suppressed catalytic activity of wild-type
RT human glutathione transferase T1-1 compared to its W234R mutant.";
RL J. Mol. Biol. 355:96-105(2006).
CC -!- FUNCTION: Conjugation of reduced glutathione to a wide number of
CC exogenous and endogenous hydrophobic electrophiles. Acts on 1,2-
CC epoxy-3-(4-nitrophenoxy)propane, phenethylisothiocyanate 4-
CC nitrobenzyl chloride and 4-nitrophenethyl bromide. Displays
CC glutathione peroxidase activity with cumene hydroperoxide.
CC -!- CATALYTIC ACTIVITY: RX + glutathione = HX + R-S-glutathione.
CC -!- SUBUNIT: Homodimer.
CC -!- SUBCELLULAR LOCATION: Cytoplasm.
CC -!- TISSUE SPECIFICITY: Found in erythrocyte. Expressed at low levels
CC in liver. In lung, expressed at low levels in Clara cells and
CC ciliated cells at the alveolar/bronchiolar junction. Absent from
CC epithelial cells of larger bronchioles.
CC -!- POLYMORPHISM: The GSTT1 gene is absent from 38% of the population.
CC The presence or absence of the GSTT1 gene is coincident with the
CC conjugator (GSST1+) and non-conjugator (GSTT1-) phenotypes
CC respectively. The GSTT1+ phenotype can catalyze the glutathione
CC conjugation of dichloromethane.
CC -!- SIMILARITY: Belongs to the GST superfamily. Theta family.
CC -!- SIMILARITY: Contains 1 GST C-terminal domain.
CC -!- SIMILARITY: Contains 1 GST N-terminal domain.
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;=GSTT1";
CC -----------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution-NoDerivs License
CC -----------------------------------------------------------------------
DR EMBL; X79389; CAA55935.1; -; mRNA.
DR EMBL; AF435971; AAL31549.1; -; mRNA.
DR EMBL; AF240786; AAG02374.1; -; Genomic_DNA.
DR EMBL; AB057594; BAB39498.1; -; Genomic_DNA.
DR EMBL; BT019951; AAV38754.1; -; mRNA.
DR EMBL; Z84718; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC007065; AAH07065.1; -; mRNA.
DR PIR; S44358; S44358.
DR RefSeq; NP_000844.2; NM_000853.2.
DR UniGene; Hs.268573; -.
DR UniGene; Hs.738514; -.
DR PDB; 2C3N; X-ray; 1.50 A; A/B/C/D=2-239.
DR PDB; 2C3Q; X-ray; 1.85 A; A/B/C/D=2-239.
DR PDB; 2C3T; X-ray; 2.40 A; A/B/C/D=2-239.
DR PDBsum; 2C3N; -.
DR PDBsum; 2C3Q; -.
DR PDBsum; 2C3T; -.
DR ProteinModelPortal; P30711; -.
DR SMR; P30711; 2-240.
DR IntAct; P30711; 1.
DR STRING; 9606.ENSP00000248935; -.
DR ChEMBL; CHEMBL2141; -.
DR DrugBank; DB00143; Glutathione.
DR PhosphoSite; P30711; -.
DR DMDM; 21264427; -.
DR PaxDb; P30711; -.
DR PRIDE; P30711; -.
DR DNASU; 2952; -.
DR Ensembl; ENST00000248935; ENSP00000248935; ENSG00000184674.
DR GeneID; 2952; -.
DR KEGG; hsa:2952; -.
DR UCSC; uc002zze.4; human.
DR CTD; 2952; -.
DR GeneCards; GC22M024952; -.
DR H-InvDB; HIX0019638; -.
DR HGNC; HGNC:4641; GSTT1.
DR MIM; 600436; gene.
DR neXtProt; NX_P30711; -.
DR PharmGKB; PA183; -.
DR eggNOG; COG0625; -.
DR HOGENOM; HOG000125747; -.
DR HOVERGEN; HBG051854; -.
DR InParanoid; P30711; -.
DR KO; K00799; -.
DR OMA; TVKQKLM; -.
DR PhylomeDB; P30711; -.
DR Reactome; REACT_111217; Metabolism.
DR SABIO-RK; P30711; -.
DR EvolutionaryTrace; P30711; -.
DR GeneWiki; GSTT1; -.
DR GenomeRNAi; 2952; -.
DR NextBio; 11698; -.
DR PRO; PR:P30711; -.
DR ArrayExpress; P30711; -.
DR Bgee; P30711; -.
DR CleanEx; HS_GSTT1; -.
DR Genevestigator; P30711; -.
DR GO; GO:0005829; C:cytosol; IDA:UniProtKB.
DR GO; GO:0004602; F:glutathione peroxidase activity; IDA:UniProtKB.
DR GO; GO:0004364; F:glutathione transferase activity; IDA:UniProtKB.
DR GO; GO:1901687; P:glutathione derivative biosynthetic process; TAS:Reactome.
DR GO; GO:0006749; P:glutathione metabolic process; IDA:UniProtKB.
DR GO; GO:0042493; P:response to drug; IEA:Ensembl.
DR GO; GO:0014070; P:response to organic cyclic compound; IEA:Ensembl.
DR GO; GO:0006805; P:xenobiotic metabolic process; TAS:Reactome.
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; IPR012336; Thioredoxin-like_fold.
DR Pfam; PF00043; GST_C; 1.
DR Pfam; PF02798; GST_N; 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; Complete proteome; Cytoplasm; Direct protein sequencing;
KW Polymorphism; Reference proteome; Transferase.
FT INIT_MET 1 1 Removed.
FT CHAIN 2 240 Glutathione S-transferase theta-1.
FT /FTId=PRO_0000185938.
FT DOMAIN 2 82 GST N-terminal.
FT DOMAIN 88 220 GST C-terminal.
FT REGION 53 54 Glutathione binding.
FT REGION 66 67 Glutathione binding.
FT BINDING 40 40 Glutathione.
FT VARIANT 21 21 A -> T (in dbSNP:rs2266635).
FT /FTId=VAR_014501.
FT VARIANT 141 141 D -> N (in dbSNP:rs2266633).
FT /FTId=VAR_014502.
FT VARIANT 169 169 V -> I (in dbSNP:rs2266637).
FT /FTId=VAR_014503.
FT VARIANT 173 173 E -> K (in dbSNP:rs2234953).
FT /FTId=VAR_014504.
FT MUTAGEN 176 176 H->Q: Increases activity towards
FT alkylhalogenides, but not hydroperoxides.
FT MUTAGEN 234 234 W->R: Facilitates binding of substrates
FT and increases catalytic activity.
FT CONFLICT 43 44 DA -> SD (in Ref. 8; AA sequence).
FT CONFLICT 45 45 F -> C (in Ref. 7; AAH07065).
FT CONFLICT 126 126 E -> G (in Ref. 1; CAA55935).
FT STRAND 3 7
FT HELIX 12 23
FT STRAND 29 32
FT HELIX 35 37
FT HELIX 39 41
FT HELIX 43 48
FT STRAND 56 59
FT STRAND 62 65
FT HELIX 67 77
FT HELIX 82 84
FT HELIX 89 101
FT HELIX 102 104
FT HELIX 106 117
FT HELIX 118 123
FT HELIX 130 150
FT TURN 151 154
FT STRAND 155 162
FT HELIX 165 179
FT HELIX 189 202
FT HELIX 204 210
FT HELIX 212 215
FT HELIX 216 219
FT HELIX 225 239
SQ SEQUENCE 240 AA; 27335 MW; BD19F2BFDEF9F619 CRC64;
MGLELYLDLL SQPCRAVYIF AKKNDIPFEL RIVDLIKGQH LSDAFAQVNP LKKVPALKDG
DFTLTESVAI LLYLTRKYKV PDYWYPQDLQ ARARVDEYLA WQHTTLRRSC LRALWHKVMF
PVFLGEPVSP QTLAATLAEL DVTLQLLEDK FLQNKAFLTG PHISLADLVA ITELMHPVGA
GCQVFEGRPK LATWRQRVEA AVGEDLFQEA HEVILKAKDF PPADPTIKQK LMPWVLAMIR
//
MIM
600436
*RECORD*
*FIELD* NO
600436
*FIELD* TI
*600436 GLUTATHIONE S-TRANSFERASE, THETA-1; GSTT1
*FIELD* TX
DESCRIPTION
Glutathione S-transferases catalyze the conjugation of glutathione to a
read morewide range of potential toxins as the first step in detoxification. The
GSTs form a superfamily whose dimeric proteins have been placed into
several multigene families. For background information on GSTs, see
138350.
CLONING
For a long time the glutathione S-transferases of the theta class were
largely overlooked because of their low activity with the model
substrate 1-chloro-2,4-dinitrobenzene (CDNB) and their failure to bind
to immobilized glutathione affinity matrices. Pemble et al. (1994)
reported the cDNA cloning of a human theta-class GST, termed GSTT1. The
deduced 239-amino acid GSTT1 protein shares 80% sequence identity with
the rat homolog.
MAPPING
By in situ hybridization studies, Webb et al. (1996) mapped the GSTT1
gene to 22q11.2, the same band where GSTT2 (600437) is localized.
MOLECULAR GENETICS
In humans, glutathione-dependent conjugation of halomethane is
polymorphic, with 60% of the population classed as conjugators and 40%
as nonconjugators. From PCR and Southern blot analyses, Pemble et al.
(1994) showed that the GSTT1 gene was absent from 38% of the population.
The presence or absence of the gene was coincident with the conjugator
(GSTT1+) and nonconjugator (GSTT1-) phenotypes, respectively. The GSTT1+
phenotype can catalyze the glutathione conjugation of dichloromethane, a
metabolic pathway that had been shown to be mutagenic in Salmonella
typhimurium mutagenicity tester strains and was believed to be
responsible for the carcinogenicity of dichloromethane in the mouse. In
humans, the GSTT1 enzyme is found in the erythrocyte and this may act as
a detoxification sink. Thus, Pemble et al. (1994) stated that
characterization of the GSTT1 polymorphism would enable a more accurate
assessment of human health risk from synthetic halomethanes and other
industrial chemicals.
Chen et al. (1996) compared the frequency of the GSTT1 null genotype in
96 patients with myelodysplastic syndromes (MDS) and 201 cancer-free
controls of similar age, race, and sex. The frequency of the GSTT1 null
genotype was 46% among MDS cases and 16% among controls. Inheritance of
the GSTT1 null genotype was calculated to confer a 4.3-fold increased
risk of MDS. The GSTM1 null genotype (138350) was not associated with an
increased risk of MDS. The authors suggested that the mechanism of the
association might be decreased detoxification of environmental or
endogenous carcinogens.
Patients with reduced ability to metabolize environmental carcinogens or
toxins may be at risk of developing aplastic anemia. GST has been
implicated in detoxifying mutagenic electrophilic compounds. Lee et al.
(2001) investigated whether homozygous deletions of GSTM1 and GSTT1
affect the likelihood of developing aplastic anemia. They found that the
incidence of GSTM1 and GSTT1 gene deletions was significantly higher for
aplastic anemia patients than for healthy controls (odds ratio = 3.1, P
= 0.01, and odds ratio = 3.1, P = 0.004, respectively). Among the
aplastic anemia patients, 17.5% had chromosomal abnormalities at the
time of diagnosis, and all aplastic anemia patients with chromosomal
abnormalities showed GSTT1 gene deletions.
Chen et al. (1996) described a method for simultaneous characterization
of GSTM1 and GSTT1 and studied the genotypes in whites and blacks. The
frequency of the null genotype for GSTM1 (GSTM1-) was higher in whites
and that for GSTT1- was higher in blacks. The observed frequency of the
'double null' genotype was not significantly different from that
predicted, assuming that the 2 polymorphisms are independent and did not
differ by race or sex.
Individual differences in the metabolism of methyl bromide, ethylene
oxide, and methylene chloride in human blood have been attributed to the
genetic polymorphism of GSTT1 (Peter et al., 1989; Pemble et al., 1994).
Depending on the GSTT1 enzyme activity toward methyl chloride measured
in erythrocytes, an individual can be assigned to 1 of 3 groups:
nonconjugators, low conjugators, and high conjugators (Hallier et al.,
1990). Several studies have shown a difference in susceptibility toward
toxic effects in nonconjugators and conjugators. Genotoxic effects such
as induction of sister chromatid exchanges (SCE) after exposure of human
blood to methyl bromide and other agents in vitro were found to be more
pronounced in nonconjugators. Even the background levels of SCE were
higher in the nonconjugator phenotype (Schroder et al., 1995). It is
generally assumed that the nonconjugator phenotype is a result of the
homozygous presence of a nonfunctional GSTT1 allele (GSTT1*0). This
allele represents a partial or complete deletion at the GSTT1 gene
locus.
Wiebel et al. (1999) studied 29 persons in 3 generations of a large
family; phenotyping and genotyping with respect to GSTT1 was performed.
The GSTT1 enzyme activity of high conjugators was twice as high as that
of low conjugators. The distribution of GSTT1 phenotypes strongly
indicated a mendelian intermediary inheritance, in which a gene-dosage
effect results in a doubled enzyme expression in the presence of 2
functional alleles. The mendelian intermediary inheritance was further
supported by the finding of a semiquantitative PCR method designed to
distinguish the 3 genotypes of GSTT1 for rapid screening of large study
groups.
Numerous studies have shown that maternal cigarette smoking during
pregnancy is associated with reduced birth weight and increased risk of
low birth weight, defined as weight less than 2,500 g. Maternal
cigarette smoking has thus been identified as the single largest
modifiable risk factor for intrauterine growth restriction in developed
countries. However, not all women who smoke cigarettes during pregnancy
have low-birth weight infants. Wang et al. (2002) studied whether the
association between maternal cigarette smoking and infant birth weight
differs by polymorphisms of 2 maternal metabolic genes: CYP1A1 and GSTT1
(600436). The CYP1A1 polymorphism was the Msp1 polymorphism (AA vs Aa
and aa); the GSTT1 polymorphism was present versus absent. Wang et al.
(2002) found that regardless of genotype, continuous maternal smoking
during pregnancy was associated with a mean reduction of 377 g in birth
weight. They found that for the CYP1A1 genotype, the estimated reduction
in birth weight was 252 g for the AA genotype group, but was 520 g for
the Aa/aa genotype group. For the GSTT1 genotype, they found the
estimated reduction in birth weight was 285 g and 642 g for the present
and absent genotype groups, respectively. When both CYP1A1 and GSTT1
genotypes were considered, Wang et al. (2002) found the greatest
reduction in birth weight among smoking mothers with the CYP1A1 Aa/aa
and GSTT1 absent genotypes. Among mothers who had not smoked during
their pregnancy or during the 3 months prior to their pregnancy,
genotype did not independently confer an adverse effect.
*FIELD* RF
1. Chen, C.-L.; Liu, Q.; Relling, M. V.: Simultaneous characterization
of glutathione S-transferase M1 and T1 polymorphisms by polymerase
chain reaction in American whites and blacks. Pharmacogenetics 6:
187-191, 1996.
2. Chen, H.; Sandler, D. P.; Taylor, J. A.; Shore, D. L.; Liu, E.;
Bloomfield, C. D.; Bell, D. A.: Increased risk for myelodysplastic
syndromes in individuals with glutathione transferase theta 1 (GSTT1)
gene defect. Lancet 347: 295-297, 1996.
3. Hallier, E.; Jager, R.; Deutschmann, S.; Bolt, H. M.; Peter, H.
: Glutathione conjugation and cytochrome P-450 metabolism of methyl
chloride in vitro. Toxicol. in Vitro 4: 513-517, 1990.
4. Lee, K. A.; Kim, S. H.; Woo, H. Y.; Hong, Y. J.; Cho, H. C.: Increased
frequencies of glutathione S-transferase (GSTM1 and GSTT1) gene deletions
in Korean patients with acquired aplastic anemia. Blood 98: 3483-3485,
2001.
5. Pemble, S.; Schroeder, K. R.; Spencer, S. R.; Meyer, D. J.; Hallier,
E.; Bolt, H. M.; Ketterer, B.; Taylor, J. B.: Human glutathione S-transferase
theta (GSTT1): cDNA cloning and the characterization of a genetic
polymorphism. Biochem. J. 300: 271-276, 1994.
6. Peter, H.; Deutschmann, S.; Reichel, C.; Hallier, E.: Metabolism
of methyl chloride by human erythrocytes. Arch. Toxicol. 63: 351-355,
1989.
7. Schroder, K. R.; Wiebel, F. A.; Reich, S.; Dannappel, D.; Bolt,
H. M.; Hallier, E.: Glutathione S-transferase (GST) theta polymorphism
influences background SCE rate. Arch. Toxicol. 69: 505-507, 1995.
8. Wang, X.; Zuckerman, B.; Pearson, C.; Kaufman, G.; Chen, C.; Wang,
G.; Niu, T.; Wise, P. H.; Bauchner, H.; Xu, X.: Maternal cigarette
smoking, metabolic gene polymorphism, and infant birth weight. JAMA 287:
195-202, 2002.
9. Webb, G.; Vaska, V.; Coggan, M.; Board, P.: Chromosomal localization
of the gene for the human theta class glutathione transferase (GSTT1). Genomics 33:
121-123, 1996.
10. Wiebel, F. A.; Dommermuth, A.; Thier, R.: The hereditary transmission
of the glutathione transferase hGSTT1-1 conjugator phenotype in a
large family. Pharmacogenetics 9: 251-256, 1999.
*FIELD* CN
Victor A. McKusick - updated: 8/16/2002
Victor A. McKusick - updated: 3/31/2000
Victor A. McKusick - updated: 9/30/1999
Victor A. McKusick - updated: 6/25/1997
*FIELD* CD
Victor A. McKusick: 3/6/1995
*FIELD* ED
tpirozzi: 07/11/2013
terry: 6/3/2009
carol: 9/23/2008
tkritzer: 8/16/2002
mgross: 4/7/2000
terry: 3/31/2000
alopez: 11/15/1999
alopez: 10/5/1999
terry: 9/30/1999
alopez: 2/6/1998
jenny: 7/1/1997
terry: 6/25/1997
jamie: 2/5/1997
mark: 3/25/1996
terry: 3/13/1996
mark: 3/23/1995
carol: 3/7/1995
carol: 3/6/1995
*RECORD*
*FIELD* NO
600436
*FIELD* TI
*600436 GLUTATHIONE S-TRANSFERASE, THETA-1; GSTT1
*FIELD* TX
DESCRIPTION
Glutathione S-transferases catalyze the conjugation of glutathione to a
read morewide range of potential toxins as the first step in detoxification. The
GSTs form a superfamily whose dimeric proteins have been placed into
several multigene families. For background information on GSTs, see
138350.
CLONING
For a long time the glutathione S-transferases of the theta class were
largely overlooked because of their low activity with the model
substrate 1-chloro-2,4-dinitrobenzene (CDNB) and their failure to bind
to immobilized glutathione affinity matrices. Pemble et al. (1994)
reported the cDNA cloning of a human theta-class GST, termed GSTT1. The
deduced 239-amino acid GSTT1 protein shares 80% sequence identity with
the rat homolog.
MAPPING
By in situ hybridization studies, Webb et al. (1996) mapped the GSTT1
gene to 22q11.2, the same band where GSTT2 (600437) is localized.
MOLECULAR GENETICS
In humans, glutathione-dependent conjugation of halomethane is
polymorphic, with 60% of the population classed as conjugators and 40%
as nonconjugators. From PCR and Southern blot analyses, Pemble et al.
(1994) showed that the GSTT1 gene was absent from 38% of the population.
The presence or absence of the gene was coincident with the conjugator
(GSTT1+) and nonconjugator (GSTT1-) phenotypes, respectively. The GSTT1+
phenotype can catalyze the glutathione conjugation of dichloromethane, a
metabolic pathway that had been shown to be mutagenic in Salmonella
typhimurium mutagenicity tester strains and was believed to be
responsible for the carcinogenicity of dichloromethane in the mouse. In
humans, the GSTT1 enzyme is found in the erythrocyte and this may act as
a detoxification sink. Thus, Pemble et al. (1994) stated that
characterization of the GSTT1 polymorphism would enable a more accurate
assessment of human health risk from synthetic halomethanes and other
industrial chemicals.
Chen et al. (1996) compared the frequency of the GSTT1 null genotype in
96 patients with myelodysplastic syndromes (MDS) and 201 cancer-free
controls of similar age, race, and sex. The frequency of the GSTT1 null
genotype was 46% among MDS cases and 16% among controls. Inheritance of
the GSTT1 null genotype was calculated to confer a 4.3-fold increased
risk of MDS. The GSTM1 null genotype (138350) was not associated with an
increased risk of MDS. The authors suggested that the mechanism of the
association might be decreased detoxification of environmental or
endogenous carcinogens.
Patients with reduced ability to metabolize environmental carcinogens or
toxins may be at risk of developing aplastic anemia. GST has been
implicated in detoxifying mutagenic electrophilic compounds. Lee et al.
(2001) investigated whether homozygous deletions of GSTM1 and GSTT1
affect the likelihood of developing aplastic anemia. They found that the
incidence of GSTM1 and GSTT1 gene deletions was significantly higher for
aplastic anemia patients than for healthy controls (odds ratio = 3.1, P
= 0.01, and odds ratio = 3.1, P = 0.004, respectively). Among the
aplastic anemia patients, 17.5% had chromosomal abnormalities at the
time of diagnosis, and all aplastic anemia patients with chromosomal
abnormalities showed GSTT1 gene deletions.
Chen et al. (1996) described a method for simultaneous characterization
of GSTM1 and GSTT1 and studied the genotypes in whites and blacks. The
frequency of the null genotype for GSTM1 (GSTM1-) was higher in whites
and that for GSTT1- was higher in blacks. The observed frequency of the
'double null' genotype was not significantly different from that
predicted, assuming that the 2 polymorphisms are independent and did not
differ by race or sex.
Individual differences in the metabolism of methyl bromide, ethylene
oxide, and methylene chloride in human blood have been attributed to the
genetic polymorphism of GSTT1 (Peter et al., 1989; Pemble et al., 1994).
Depending on the GSTT1 enzyme activity toward methyl chloride measured
in erythrocytes, an individual can be assigned to 1 of 3 groups:
nonconjugators, low conjugators, and high conjugators (Hallier et al.,
1990). Several studies have shown a difference in susceptibility toward
toxic effects in nonconjugators and conjugators. Genotoxic effects such
as induction of sister chromatid exchanges (SCE) after exposure of human
blood to methyl bromide and other agents in vitro were found to be more
pronounced in nonconjugators. Even the background levels of SCE were
higher in the nonconjugator phenotype (Schroder et al., 1995). It is
generally assumed that the nonconjugator phenotype is a result of the
homozygous presence of a nonfunctional GSTT1 allele (GSTT1*0). This
allele represents a partial or complete deletion at the GSTT1 gene
locus.
Wiebel et al. (1999) studied 29 persons in 3 generations of a large
family; phenotyping and genotyping with respect to GSTT1 was performed.
The GSTT1 enzyme activity of high conjugators was twice as high as that
of low conjugators. The distribution of GSTT1 phenotypes strongly
indicated a mendelian intermediary inheritance, in which a gene-dosage
effect results in a doubled enzyme expression in the presence of 2
functional alleles. The mendelian intermediary inheritance was further
supported by the finding of a semiquantitative PCR method designed to
distinguish the 3 genotypes of GSTT1 for rapid screening of large study
groups.
Numerous studies have shown that maternal cigarette smoking during
pregnancy is associated with reduced birth weight and increased risk of
low birth weight, defined as weight less than 2,500 g. Maternal
cigarette smoking has thus been identified as the single largest
modifiable risk factor for intrauterine growth restriction in developed
countries. However, not all women who smoke cigarettes during pregnancy
have low-birth weight infants. Wang et al. (2002) studied whether the
association between maternal cigarette smoking and infant birth weight
differs by polymorphisms of 2 maternal metabolic genes: CYP1A1 and GSTT1
(600436). The CYP1A1 polymorphism was the Msp1 polymorphism (AA vs Aa
and aa); the GSTT1 polymorphism was present versus absent. Wang et al.
(2002) found that regardless of genotype, continuous maternal smoking
during pregnancy was associated with a mean reduction of 377 g in birth
weight. They found that for the CYP1A1 genotype, the estimated reduction
in birth weight was 252 g for the AA genotype group, but was 520 g for
the Aa/aa genotype group. For the GSTT1 genotype, they found the
estimated reduction in birth weight was 285 g and 642 g for the present
and absent genotype groups, respectively. When both CYP1A1 and GSTT1
genotypes were considered, Wang et al. (2002) found the greatest
reduction in birth weight among smoking mothers with the CYP1A1 Aa/aa
and GSTT1 absent genotypes. Among mothers who had not smoked during
their pregnancy or during the 3 months prior to their pregnancy,
genotype did not independently confer an adverse effect.
*FIELD* RF
1. Chen, C.-L.; Liu, Q.; Relling, M. V.: Simultaneous characterization
of glutathione S-transferase M1 and T1 polymorphisms by polymerase
chain reaction in American whites and blacks. Pharmacogenetics 6:
187-191, 1996.
2. Chen, H.; Sandler, D. P.; Taylor, J. A.; Shore, D. L.; Liu, E.;
Bloomfield, C. D.; Bell, D. A.: Increased risk for myelodysplastic
syndromes in individuals with glutathione transferase theta 1 (GSTT1)
gene defect. Lancet 347: 295-297, 1996.
3. Hallier, E.; Jager, R.; Deutschmann, S.; Bolt, H. M.; Peter, H.
: Glutathione conjugation and cytochrome P-450 metabolism of methyl
chloride in vitro. Toxicol. in Vitro 4: 513-517, 1990.
4. Lee, K. A.; Kim, S. H.; Woo, H. Y.; Hong, Y. J.; Cho, H. C.: Increased
frequencies of glutathione S-transferase (GSTM1 and GSTT1) gene deletions
in Korean patients with acquired aplastic anemia. Blood 98: 3483-3485,
2001.
5. Pemble, S.; Schroeder, K. R.; Spencer, S. R.; Meyer, D. J.; Hallier,
E.; Bolt, H. M.; Ketterer, B.; Taylor, J. B.: Human glutathione S-transferase
theta (GSTT1): cDNA cloning and the characterization of a genetic
polymorphism. Biochem. J. 300: 271-276, 1994.
6. Peter, H.; Deutschmann, S.; Reichel, C.; Hallier, E.: Metabolism
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*FIELD* CN
Victor A. McKusick - updated: 8/16/2002
Victor A. McKusick - updated: 3/31/2000
Victor A. McKusick - updated: 9/30/1999
Victor A. McKusick - updated: 6/25/1997
*FIELD* CD
Victor A. McKusick: 3/6/1995
*FIELD* ED
tpirozzi: 07/11/2013
terry: 6/3/2009
carol: 9/23/2008
tkritzer: 8/16/2002
mgross: 4/7/2000
terry: 3/31/2000
alopez: 11/15/1999
alopez: 10/5/1999
terry: 9/30/1999
alopez: 2/6/1998
jenny: 7/1/1997
terry: 6/25/1997
jamie: 2/5/1997
mark: 3/25/1996
terry: 3/13/1996
mark: 3/23/1995
carol: 3/7/1995
carol: 3/6/1995