Full text data of GSTO1
GSTO1
(GSTTLP28)
[Confidence: medium (present in either hRBCD or BSc_CH or PM22954596)]
Glutathione S-transferase omega-1; GSTO-1; 2.5.1.18 (Glutathione S-transferase omega 1-1; GSTO 1-1; Glutathione-dependent dehydroascorbate reductase; 1.8.5.1; Monomethylarsonic acid reductase; MMA(V) reductase; 1.20.4.2; S-(Phenacyl)glutathione reductase; SPG-R)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
Glutathione S-transferase omega-1; GSTO-1; 2.5.1.18 (Glutathione S-transferase omega 1-1; GSTO 1-1; Glutathione-dependent dehydroascorbate reductase; 1.8.5.1; Monomethylarsonic acid reductase; MMA(V) reductase; 1.20.4.2; S-(Phenacyl)glutathione reductase; SPG-R)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
hRBCD
IPI00019755
IPI00019755 Hypothetical protein DKFZp686H13163 Exhibits glutathione-dependent thiol transferase and dehydroascorbate reductase activities, 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
IPI00019755 Hypothetical protein DKFZp686H13163 Exhibits glutathione-dependent thiol transferase and dehydroascorbate reductase activities, 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
P78417
ID GSTO1_HUMAN Reviewed; 241 AA.
AC P78417; D3DRA3; F5H7H0; Q5TA03; Q7Z3T2;
DT 15-JUL-1999, integrated into UniProtKB/Swiss-Prot.
read moreDT 01-JAN-1998, sequence version 2.
DT 22-JAN-2014, entry version 146.
DE RecName: Full=Glutathione S-transferase omega-1;
DE Short=GSTO-1;
DE EC=2.5.1.18;
DE AltName: Full=Glutathione S-transferase omega 1-1;
DE Short=GSTO 1-1;
DE AltName: Full=Glutathione-dependent dehydroascorbate reductase;
DE EC=1.8.5.1;
DE AltName: Full=Monomethylarsonic acid reductase;
DE Short=MMA(V) reductase;
DE EC=1.20.4.2;
DE AltName: Full=S-(Phenacyl)glutathione reductase;
DE Short=SPG-R;
GN Name=GSTO1; Synonyms=GSTTLP28;
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] (ISOFORM 1).
RC TISSUE=Placenta;
RA Kodym R., Story M.D.;
RT "Cloning of the human homolog to a mouse protein, differentially
RT expressed in lymphoma cells with different susceptibility to radiation
RT induced apoptosis.";
RL Submitted (FEB-1997) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), X-RAY CRYSTALLOGRAPHY (2.0
RP ANGSTROMS) IN COMPLEX WITH GLUTATHIONE, FUNCTION, CATALYTIC ACTIVITY,
RP ACTIVE SITE, SUBUNIT, AND TISSUE SPECIFICITY.
RC TISSUE=Fetus;
RX PubMed=10783391; DOI=10.1074/jbc.M001706200;
RA Board P.G., Coggan M., Chelvanayagam G., Easteal S., Jermiin L.S.,
RA Schulte G.K., Danley D.E., Hoth L.R., Griffor M.C., Kamath A.V.,
RA Rosner M.H., Chrunyk B.A., Perregaux D.E., Gabel C.A., Geoghegan K.F.,
RA Pandit J.;
RT "Identification, characterization, and crystal structure of the Omega
RT class glutathione transferases.";
RL J. Biol. Chem. 275:24798-24806(2000).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS ASP-140; GLU-155 DEL;
RP LYS-208 AND VAL-236.
RX PubMed=12928150;
RA Yu L., Kalla K., Guthrie E., Vidrine A., Klimecki W.T.;
RT "Genetic variation in genes associated with arsenic metabolism:
RT glutathione S-transferase omega 1-1 and purine nucleoside
RT phosphorylase polymorphisms in European and indigenous Americans.";
RL Environ. Health Perspect. 111:1421-1427(2003).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Uterus;
RX PubMed=17974005; DOI=10.1186/1471-2164-8-399;
RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U.,
RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H.,
RA Heubner D., Hoerlein A., Michel G., Wedler H., Koehrer K.,
RA Ottenwaelder B., Poustka A., Wiemann S., Schupp I.;
RT "The full-ORF clone resource of the German cDNA consortium.";
RL BMC Genomics 8:399-399(2007).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15164054; DOI=10.1038/nature02462;
RA Deloukas P., Earthrowl M.E., Grafham D.V., Rubenfield M., French L.,
RA Steward C.A., Sims S.K., Jones M.C., Searle S., Scott C., Howe K.,
RA Hunt S.E., Andrews T.D., Gilbert J.G.R., Swarbreck D., Ashurst J.L.,
RA Taylor A., Battles J., Bird C.P., Ainscough R., Almeida J.P.,
RA Ashwell R.I.S., Ambrose K.D., Babbage A.K., Bagguley C.L., Bailey J.,
RA Banerjee R., Bates K., Beasley H., Bray-Allen S., Brown A.J.,
RA Brown J.Y., Burford D.C., Burrill W., Burton J., Cahill P., Camire D.,
RA Carter N.P., Chapman J.C., Clark S.Y., Clarke G., Clee C.M., Clegg S.,
RA Corby N., Coulson A., Dhami P., Dutta I., Dunn M., Faulkner L.,
RA Frankish A., Frankland J.A., Garner P., Garnett J., Gribble S.,
RA Griffiths C., Grocock R., Gustafson E., Hammond S., Harley J.L.,
RA Hart E., Heath P.D., Ho T.P., Hopkins B., Horne J., Howden P.J.,
RA Huckle E., Hynds C., Johnson C., Johnson D., Kana A., Kay M.,
RA Kimberley A.M., Kershaw J.K., Kokkinaki M., Laird G.K., Lawlor S.,
RA Lee H.M., Leongamornlert D.A., Laird G., Lloyd C., Lloyd D.M.,
RA Loveland J., Lovell J., McLaren S., McLay K.E., McMurray A.,
RA Mashreghi-Mohammadi M., Matthews L., Milne S., Nickerson T.,
RA Nguyen M., Overton-Larty E., Palmer S.A., Pearce A.V., Peck A.I.,
RA Pelan S., Phillimore B., Porter K., Rice C.M., Rogosin A., Ross M.T.,
RA Sarafidou T., Sehra H.K., Shownkeen R., Skuce C.D., Smith M.,
RA Standring L., Sycamore N., Tester J., Thorpe A., Torcasso W.,
RA Tracey A., Tromans A., Tsolas J., Wall M., Walsh J., Wang H.,
RA Weinstock K., West A.P., Willey D.L., Whitehead S.L., Wilming L.,
RA Wray P.W., Young L., Chen Y., Lovering R.C., Moschonas N.K.,
RA Siebert R., Fechtel K., Bentley D., Durbin R.M., Hubbard T.,
RA Doucette-Stamm L., Beck S., Smith D.R., Rogers J.;
RT "The DNA sequence and comparative analysis of human chromosome 10.";
RL Nature 429:375-381(2004).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L.,
RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Eye;
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 12-21; 58-65; 133-139 AND 149-156, AND MASS
RP SPECTROMETRY.
RC TISSUE=Liver;
RX PubMed=11271497;
RX DOI=10.1002/1522-2683(200011)21:17<3785::AID-ELPS3785>3.0.CO;2-2;
RA Hubbard M.J., McHugh N.J.;
RT "Human ERp29: isolation, primary structural characterisation and two-
RT dimensional gel mapping.";
RL Electrophoresis 21:3785-3796(2000).
RN [9]
RP PARTIAL PROTEIN SEQUENCE, FUNCTION, CATALYTIC ACTIVITY,
RP BIOPHYSICOCHEMICAL PROPERTIES, SUBCELLULAR LOCATION, AND MASS
RP SPECTROMETRY.
RC TISSUE=Liver;
RX PubMed=11511179; DOI=10.1021/tx010052h;
RA Zakharyan R.A., Sampayo-Reyes A., Healy S.M., Tsaprailis G.,
RA Board P.G., Liebler D.C., Aposhian H.V.;
RT "Human monomethylarsonic acid (MMA(V)) reductase is a member of the
RT glutathione-S-transferase superfamily.";
RL Chem. Res. Toxicol. 14:1051-1057(2001).
RN [10]
RP FUNCTION, MUTAGENESIS OF CYS-32, BIOPHYSICOCHEMICAL PROPERTIES, AND
RP CATALYTIC ACTIVITY.
RX PubMed=17226937; DOI=10.1021/tx600305y;
RA Board P.G., Anders M.W.;
RT "Glutathione transferase omega 1 catalyzes the reduction of S-
RT (phenacyl)glutathiones to acetophenones.";
RL Chem. Res. Toxicol. 20:149-154(2007).
RN [11]
RP FUNCTION, AND CATALYTIC ACTIVITY.
RX PubMed=18028863; DOI=10.1016/j.ab.2007.09.029;
RA Board P.G., Coggan M., Cappello J., Zhou H., Oakley A.J., Anders M.W.;
RT "S-(4-Nitrophenacyl)glutathione is a specific substrate for
RT glutathione transferase omega 1-1.";
RL Anal. Biochem. 374:25-30(2008).
RN [12]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT SER-2, MASS SPECTROMETRY, AND
RP CLEAVAGE OF INITIATOR METHIONINE.
RX PubMed=19413330; DOI=10.1021/ac9004309;
RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J.,
RA Mohammed S.;
RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in
RT a refined SCX-based approach.";
RL Anal. Chem. 81:4493-4501(2009).
RN [13]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-57; LYS-143; LYS-148 AND
RP LYS-152, 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 [14]
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 [15]
RP X-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS) OF VARIANT GLU-155 DEL,
RP FUNCTION, CATALYTIC ACTIVITY, SUBUNIT, AND CHARACTERIZATION OF
RP VARIANTS ASP-140 AND GLU-155 DEL.
RX PubMed=21106529; DOI=10.1074/jbc.M110.197822;
RA Zhou H., Brock J., Casarotto M.G., Oakley A.J., Board P.G.;
RT "Novel folding and stability defects cause a deficiency of human
RT glutathione transferase omega 1.";
RL J. Biol. Chem. 286:4271-4279(2011).
RN [16]
RP VARIANTS ASP-140 AND GLU-155 DEL.
RX PubMed=12618591; DOI=10.1097/00008571-200303000-00003;
RA Whitbread A.K., Tetlow N., Eyre H.J., Sutherland G.R., Board P.G.;
RT "Characterization of the human Omega class glutathione transferase
RT genes and associated polymorphisms.";
RL Pharmacogenetics 13:131-144(2003).
CC -!- FUNCTION: Exhibits glutathione-dependent thiol transferase and
CC dehydroascorbate reductase activities. Has S-(phenacyl)glutathione
CC reductase activity. Has also glutathione S-transferase activity.
CC Participates in the biotransformation of inorganic arsenic and
CC reduces monomethylarsonic acid (MMA) and dimethylarsonic acid.
CC -!- CATALYTIC ACTIVITY: RX + glutathione = HX + R-S-glutathione.
CC -!- CATALYTIC ACTIVITY: 2 glutathione + dehydroascorbate = glutathione
CC disulfide + ascorbate.
CC -!- CATALYTIC ACTIVITY: Methylarsonate + 2 glutathione =
CC methylarsonite + glutathione disulfide + H(2)O.
CC -!- ENZYME REGULATION: Monomethylarsonic acid reductase activity is
CC competitively inhibited by 1-chloro 2,4-dinitrobenzene (CDNB) and
CC by deoxycholate.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC pH dependence:
CC Optimum pH is 8;
CC -!- SUBUNIT: Homodimer.
CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytosol.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=P78417-1; Sequence=Displayed;
CC Name=2;
CC IsoId=P78417-2; Sequence=VSP_045820;
CC Name=3;
CC IsoId=P78417-3; Sequence=VSP_045819;
CC -!- TISSUE SPECIFICITY: Ubiquitous. Highest expression in liver,
CC pancreas, skeletal muscle, spleen, thymus, colon, blood leukocyte
CC and heart. Lowest expression in brain, placenta and lung.
CC -!- SIMILARITY: Belongs to the GST superfamily. Omega family.
CC -!- SIMILARITY: Contains 1 GST C-terminal domain.
CC -!- SIMILARITY: Contains 1 GST N-terminal domain.
CC -!- SEQUENCE CAUTION:
CC Sequence=CAD97673.1; Type=Erroneous initiation; Note=Translation N-terminally shortened;
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DR EMBL; U90313; AAB70109.1; -; mRNA.
DR EMBL; AF212303; AAF73376.1; -; mRNA.
DR EMBL; AY817669; AAV68046.1; -; Genomic_DNA.
DR EMBL; BX537431; CAD97673.1; ALT_INIT; mRNA.
DR EMBL; AL139341; CAI17224.1; -; Genomic_DNA.
DR EMBL; CH471066; EAW49601.1; -; Genomic_DNA.
DR EMBL; CH471066; EAW49602.1; -; Genomic_DNA.
DR EMBL; CH471066; EAW49603.1; -; Genomic_DNA.
DR EMBL; BC000127; AAH00127.1; -; mRNA.
DR RefSeq; NP_001177931.1; NM_001191002.1.
DR RefSeq; NP_001177932.1; NM_001191003.1.
DR RefSeq; NP_004823.1; NM_004832.2.
DR UniGene; Hs.190028; -.
DR PDB; 1EEM; X-ray; 2.00 A; A=1-241.
DR PDB; 3LFL; X-ray; 2.10 A; A/B/C=1-241.
DR PDB; 3VLN; X-ray; 1.70 A; A=1-241.
DR PDB; 4IS0; X-ray; 1.72 A; A=1-241.
DR PDBsum; 1EEM; -.
DR PDBsum; 3LFL; -.
DR PDBsum; 3VLN; -.
DR PDBsum; 4IS0; -.
DR ProteinModelPortal; P78417; -.
DR SMR; P78417; 3-241.
DR IntAct; P78417; 7.
DR MINT; MINT-1384709; -.
DR STRING; 9606.ENSP00000358727; -.
DR BindingDB; P78417; -.
DR ChEMBL; CHEMBL3174; -.
DR DrugBank; DB00143; Glutathione.
DR PhosphoSite; P78417; -.
DR DMDM; 6016173; -.
DR OGP; P78417; -.
DR UCD-2DPAGE; P78417; -.
DR PaxDb; P78417; -.
DR PeptideAtlas; P78417; -.
DR PRIDE; P78417; -.
DR Ensembl; ENST00000369710; ENSP00000358724; ENSG00000148834.
DR Ensembl; ENST00000369713; ENSP00000358727; ENSG00000148834.
DR Ensembl; ENST00000539281; ENSP00000441488; ENSG00000148834.
DR GeneID; 9446; -.
DR KEGG; hsa:9446; -.
DR UCSC; uc021pxs.1; human.
DR CTD; 9446; -.
DR GeneCards; GC10P106004; -.
DR HGNC; HGNC:13312; GSTO1.
DR HPA; HPA037604; -.
DR MIM; 605482; gene.
DR neXtProt; NX_P78417; -.
DR PharmGKB; PA133787054; -.
DR eggNOG; COG0625; -.
DR HOGENOM; HOG000006560; -.
DR HOVERGEN; HBG051853; -.
DR InParanoid; P78417; -.
DR KO; K00799; -.
DR OMA; QPEIKFS; -.
DR OrthoDB; EOG71CFNG; -.
DR PhylomeDB; P78417; -.
DR BioCyc; MetaCyc:HS07564-MONOMER; -.
DR Reactome; REACT_111217; Metabolism.
DR Reactome; REACT_116125; Disease.
DR ChiTaRS; GSTO1; human.
DR EvolutionaryTrace; P78417; -.
DR GeneWiki; GSTO1; -.
DR GenomeRNAi; 9446; -.
DR NextBio; 35384; -.
DR PRO; PR:P78417; -.
DR ArrayExpress; P78417; -.
DR Bgee; P78417; -.
DR CleanEx; HS_GSTO1; -.
DR Genevestigator; P78417; -.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0045174; F:glutathione dehydrogenase (ascorbate) activity; IDA:UniProtKB.
DR GO; GO:0004364; F:glutathione transferase activity; IDA:UniProtKB.
DR GO; GO:0050610; F:methylarsonate reductase activity; IEA:UniProtKB-EC.
DR GO; GO:0071243; P:cellular response to arsenic-containing substance; IDA:UniProtKB.
DR GO; GO:1901687; P:glutathione derivative biosynthetic process; TAS:Reactome.
DR GO; GO:0019852; P:L-ascorbic acid metabolic process; IDA:UniProtKB.
DR GO; GO:0060315; P:negative regulation of ryanodine-sensitive calcium-release channel activity; IDA:BHF-UCL.
DR GO; GO:0060316; P:positive regulation of ryanodine-sensitive calcium-release channel activity; IDA:BHF-UCL.
DR GO; GO:0014810; P:positive regulation of skeletal muscle contraction by regulation of release of sequestered calcium ion; IC:BHF-UCL.
DR GO; GO:0010881; P:regulation of cardiac muscle contraction by regulation of the release of sequestered calcium ion; IC:BHF-UCL.
DR GO; GO:0042178; P:xenobiotic catabolic 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; IPR005442; GST_omega.
DR InterPro; IPR012336; Thioredoxin-like_fold.
DR Pfam; PF00043; GST_C; 1.
DR Pfam; PF13417; GST_N_3; 1.
DR PRINTS; PR01625; GSTRNSFRASEO.
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; Alternative splicing; Complete proteome;
KW Cytoplasm; Direct protein sequencing; Oxidoreductase; Polymorphism;
KW Reference proteome; Transferase.
FT INIT_MET 1 1 Removed.
FT CHAIN 2 241 Glutathione S-transferase omega-1.
FT /FTId=PRO_0000185884.
FT DOMAIN 22 101 GST N-terminal.
FT DOMAIN 106 230 GST C-terminal.
FT REGION 85 86 Glutathione binding.
FT ACT_SITE 32 32 Nucleophile.
FT BINDING 59 59 Glutathione.
FT BINDING 72 72 Glutathione; via amide nitrogen and
FT carbonyl oxygen.
FT MOD_RES 2 2 N-acetylserine.
FT MOD_RES 57 57 N6-acetyllysine.
FT MOD_RES 143 143 N6-acetyllysine.
FT MOD_RES 148 148 N6-acetyllysine.
FT MOD_RES 152 152 N6-acetyllysine.
FT VAR_SEQ 1 28 Missing (in isoform 3).
FT /FTId=VSP_045819.
FT VAR_SEQ 123 155 Missing (in isoform 2).
FT /FTId=VSP_045820.
FT VARIANT 32 32 C -> Y (in dbSNP:rs45529437).
FT /FTId=VAR_061231.
FT VARIANT 86 86 S -> C (in dbSNP:rs11509436).
FT /FTId=VAR_029269.
FT VARIANT 140 140 A -> D (in allele GSTO1*C; no effect on
FT protein stability; dbSNP:rs4925).
FT /FTId=VAR_016811.
FT VARIANT 155 155 Missing (in allele GSTO1*B; decreased
FT protein stability).
FT /FTId=VAR_016813.
FT VARIANT 208 208 E -> K (in dbSNP:rs11509438).
FT /FTId=VAR_024484.
FT VARIANT 236 236 A -> V (in dbSNP:rs11509439).
FT /FTId=VAR_026583.
FT MUTAGEN 32 32 C->A: Loss of activity.
FT HELIX 4 6
FT STRAND 24 28
FT HELIX 33 45
FT STRAND 49 54
FT STRAND 56 58
FT HELIX 63 66
FT STRAND 74 76
FT STRAND 82 85
FT HELIX 86 96
FT HELIX 107 120
FT HELIX 123 131
FT HELIX 136 160
FT STRAND 162 164
FT STRAND 167 169
FT HELIX 172 184
FT TURN 185 188
FT HELIX 190 192
FT STRAND 193 195
FT HELIX 197 207
FT HELIX 210 215
FT HELIX 219 229
FT TURN 230 232
FT HELIX 236 238
SQ SEQUENCE 241 AA; 27566 MW; 9134ABA265F5C87E CRC64;
MSGESARSLG KGSAPPGPVP EGSIRIYSMR FCPFAERTRL VLKAKGIRHE VININLKNKP
EWFFKKNPFG LVPVLENSQG QLIYESAITC EYLDEAYPGK KLLPDDPYEK ACQKMILELF
SKVPSLVGSF IRSQNKEDYA GLKEEFRKEF TKLEEVLTNK KTTFFGGNSI SMIDYLIWPW
FERLEAMKLN ECVDHTPKLK LWMAAMKEDP TVSALLTSEK DWQGFLELYL QNSPEACDYG
L
//
ID GSTO1_HUMAN Reviewed; 241 AA.
AC P78417; D3DRA3; F5H7H0; Q5TA03; Q7Z3T2;
DT 15-JUL-1999, integrated into UniProtKB/Swiss-Prot.
read moreDT 01-JAN-1998, sequence version 2.
DT 22-JAN-2014, entry version 146.
DE RecName: Full=Glutathione S-transferase omega-1;
DE Short=GSTO-1;
DE EC=2.5.1.18;
DE AltName: Full=Glutathione S-transferase omega 1-1;
DE Short=GSTO 1-1;
DE AltName: Full=Glutathione-dependent dehydroascorbate reductase;
DE EC=1.8.5.1;
DE AltName: Full=Monomethylarsonic acid reductase;
DE Short=MMA(V) reductase;
DE EC=1.20.4.2;
DE AltName: Full=S-(Phenacyl)glutathione reductase;
DE Short=SPG-R;
GN Name=GSTO1; Synonyms=GSTTLP28;
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] (ISOFORM 1).
RC TISSUE=Placenta;
RA Kodym R., Story M.D.;
RT "Cloning of the human homolog to a mouse protein, differentially
RT expressed in lymphoma cells with different susceptibility to radiation
RT induced apoptosis.";
RL Submitted (FEB-1997) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), X-RAY CRYSTALLOGRAPHY (2.0
RP ANGSTROMS) IN COMPLEX WITH GLUTATHIONE, FUNCTION, CATALYTIC ACTIVITY,
RP ACTIVE SITE, SUBUNIT, AND TISSUE SPECIFICITY.
RC TISSUE=Fetus;
RX PubMed=10783391; DOI=10.1074/jbc.M001706200;
RA Board P.G., Coggan M., Chelvanayagam G., Easteal S., Jermiin L.S.,
RA Schulte G.K., Danley D.E., Hoth L.R., Griffor M.C., Kamath A.V.,
RA Rosner M.H., Chrunyk B.A., Perregaux D.E., Gabel C.A., Geoghegan K.F.,
RA Pandit J.;
RT "Identification, characterization, and crystal structure of the Omega
RT class glutathione transferases.";
RL J. Biol. Chem. 275:24798-24806(2000).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS ASP-140; GLU-155 DEL;
RP LYS-208 AND VAL-236.
RX PubMed=12928150;
RA Yu L., Kalla K., Guthrie E., Vidrine A., Klimecki W.T.;
RT "Genetic variation in genes associated with arsenic metabolism:
RT glutathione S-transferase omega 1-1 and purine nucleoside
RT phosphorylase polymorphisms in European and indigenous Americans.";
RL Environ. Health Perspect. 111:1421-1427(2003).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Uterus;
RX PubMed=17974005; DOI=10.1186/1471-2164-8-399;
RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U.,
RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H.,
RA Heubner D., Hoerlein A., Michel G., Wedler H., Koehrer K.,
RA Ottenwaelder B., Poustka A., Wiemann S., Schupp I.;
RT "The full-ORF clone resource of the German cDNA consortium.";
RL BMC Genomics 8:399-399(2007).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15164054; DOI=10.1038/nature02462;
RA Deloukas P., Earthrowl M.E., Grafham D.V., Rubenfield M., French L.,
RA Steward C.A., Sims S.K., Jones M.C., Searle S., Scott C., Howe K.,
RA Hunt S.E., Andrews T.D., Gilbert J.G.R., Swarbreck D., Ashurst J.L.,
RA Taylor A., Battles J., Bird C.P., Ainscough R., Almeida J.P.,
RA Ashwell R.I.S., Ambrose K.D., Babbage A.K., Bagguley C.L., Bailey J.,
RA Banerjee R., Bates K., Beasley H., Bray-Allen S., Brown A.J.,
RA Brown J.Y., Burford D.C., Burrill W., Burton J., Cahill P., Camire D.,
RA Carter N.P., Chapman J.C., Clark S.Y., Clarke G., Clee C.M., Clegg S.,
RA Corby N., Coulson A., Dhami P., Dutta I., Dunn M., Faulkner L.,
RA Frankish A., Frankland J.A., Garner P., Garnett J., Gribble S.,
RA Griffiths C., Grocock R., Gustafson E., Hammond S., Harley J.L.,
RA Hart E., Heath P.D., Ho T.P., Hopkins B., Horne J., Howden P.J.,
RA Huckle E., Hynds C., Johnson C., Johnson D., Kana A., Kay M.,
RA Kimberley A.M., Kershaw J.K., Kokkinaki M., Laird G.K., Lawlor S.,
RA Lee H.M., Leongamornlert D.A., Laird G., Lloyd C., Lloyd D.M.,
RA Loveland J., Lovell J., McLaren S., McLay K.E., McMurray A.,
RA Mashreghi-Mohammadi M., Matthews L., Milne S., Nickerson T.,
RA Nguyen M., Overton-Larty E., Palmer S.A., Pearce A.V., Peck A.I.,
RA Pelan S., Phillimore B., Porter K., Rice C.M., Rogosin A., Ross M.T.,
RA Sarafidou T., Sehra H.K., Shownkeen R., Skuce C.D., Smith M.,
RA Standring L., Sycamore N., Tester J., Thorpe A., Torcasso W.,
RA Tracey A., Tromans A., Tsolas J., Wall M., Walsh J., Wang H.,
RA Weinstock K., West A.P., Willey D.L., Whitehead S.L., Wilming L.,
RA Wray P.W., Young L., Chen Y., Lovering R.C., Moschonas N.K.,
RA Siebert R., Fechtel K., Bentley D., Durbin R.M., Hubbard T.,
RA Doucette-Stamm L., Beck S., Smith D.R., Rogers J.;
RT "The DNA sequence and comparative analysis of human chromosome 10.";
RL Nature 429:375-381(2004).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L.,
RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Eye;
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 12-21; 58-65; 133-139 AND 149-156, AND MASS
RP SPECTROMETRY.
RC TISSUE=Liver;
RX PubMed=11271497;
RX DOI=10.1002/1522-2683(200011)21:17<3785::AID-ELPS3785>3.0.CO;2-2;
RA Hubbard M.J., McHugh N.J.;
RT "Human ERp29: isolation, primary structural characterisation and two-
RT dimensional gel mapping.";
RL Electrophoresis 21:3785-3796(2000).
RN [9]
RP PARTIAL PROTEIN SEQUENCE, FUNCTION, CATALYTIC ACTIVITY,
RP BIOPHYSICOCHEMICAL PROPERTIES, SUBCELLULAR LOCATION, AND MASS
RP SPECTROMETRY.
RC TISSUE=Liver;
RX PubMed=11511179; DOI=10.1021/tx010052h;
RA Zakharyan R.A., Sampayo-Reyes A., Healy S.M., Tsaprailis G.,
RA Board P.G., Liebler D.C., Aposhian H.V.;
RT "Human monomethylarsonic acid (MMA(V)) reductase is a member of the
RT glutathione-S-transferase superfamily.";
RL Chem. Res. Toxicol. 14:1051-1057(2001).
RN [10]
RP FUNCTION, MUTAGENESIS OF CYS-32, BIOPHYSICOCHEMICAL PROPERTIES, AND
RP CATALYTIC ACTIVITY.
RX PubMed=17226937; DOI=10.1021/tx600305y;
RA Board P.G., Anders M.W.;
RT "Glutathione transferase omega 1 catalyzes the reduction of S-
RT (phenacyl)glutathiones to acetophenones.";
RL Chem. Res. Toxicol. 20:149-154(2007).
RN [11]
RP FUNCTION, AND CATALYTIC ACTIVITY.
RX PubMed=18028863; DOI=10.1016/j.ab.2007.09.029;
RA Board P.G., Coggan M., Cappello J., Zhou H., Oakley A.J., Anders M.W.;
RT "S-(4-Nitrophenacyl)glutathione is a specific substrate for
RT glutathione transferase omega 1-1.";
RL Anal. Biochem. 374:25-30(2008).
RN [12]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT SER-2, MASS SPECTROMETRY, AND
RP CLEAVAGE OF INITIATOR METHIONINE.
RX PubMed=19413330; DOI=10.1021/ac9004309;
RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J.,
RA Mohammed S.;
RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in
RT a refined SCX-based approach.";
RL Anal. Chem. 81:4493-4501(2009).
RN [13]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-57; LYS-143; LYS-148 AND
RP LYS-152, 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 [14]
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 [15]
RP X-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS) OF VARIANT GLU-155 DEL,
RP FUNCTION, CATALYTIC ACTIVITY, SUBUNIT, AND CHARACTERIZATION OF
RP VARIANTS ASP-140 AND GLU-155 DEL.
RX PubMed=21106529; DOI=10.1074/jbc.M110.197822;
RA Zhou H., Brock J., Casarotto M.G., Oakley A.J., Board P.G.;
RT "Novel folding and stability defects cause a deficiency of human
RT glutathione transferase omega 1.";
RL J. Biol. Chem. 286:4271-4279(2011).
RN [16]
RP VARIANTS ASP-140 AND GLU-155 DEL.
RX PubMed=12618591; DOI=10.1097/00008571-200303000-00003;
RA Whitbread A.K., Tetlow N., Eyre H.J., Sutherland G.R., Board P.G.;
RT "Characterization of the human Omega class glutathione transferase
RT genes and associated polymorphisms.";
RL Pharmacogenetics 13:131-144(2003).
CC -!- FUNCTION: Exhibits glutathione-dependent thiol transferase and
CC dehydroascorbate reductase activities. Has S-(phenacyl)glutathione
CC reductase activity. Has also glutathione S-transferase activity.
CC Participates in the biotransformation of inorganic arsenic and
CC reduces monomethylarsonic acid (MMA) and dimethylarsonic acid.
CC -!- CATALYTIC ACTIVITY: RX + glutathione = HX + R-S-glutathione.
CC -!- CATALYTIC ACTIVITY: 2 glutathione + dehydroascorbate = glutathione
CC disulfide + ascorbate.
CC -!- CATALYTIC ACTIVITY: Methylarsonate + 2 glutathione =
CC methylarsonite + glutathione disulfide + H(2)O.
CC -!- ENZYME REGULATION: Monomethylarsonic acid reductase activity is
CC competitively inhibited by 1-chloro 2,4-dinitrobenzene (CDNB) and
CC by deoxycholate.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC pH dependence:
CC Optimum pH is 8;
CC -!- SUBUNIT: Homodimer.
CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytosol.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=P78417-1; Sequence=Displayed;
CC Name=2;
CC IsoId=P78417-2; Sequence=VSP_045820;
CC Name=3;
CC IsoId=P78417-3; Sequence=VSP_045819;
CC -!- TISSUE SPECIFICITY: Ubiquitous. Highest expression in liver,
CC pancreas, skeletal muscle, spleen, thymus, colon, blood leukocyte
CC and heart. Lowest expression in brain, placenta and lung.
CC -!- SIMILARITY: Belongs to the GST superfamily. Omega family.
CC -!- SIMILARITY: Contains 1 GST C-terminal domain.
CC -!- SIMILARITY: Contains 1 GST N-terminal domain.
CC -!- SEQUENCE CAUTION:
CC Sequence=CAD97673.1; Type=Erroneous initiation; Note=Translation N-terminally shortened;
CC -----------------------------------------------------------------------
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DR EMBL; U90313; AAB70109.1; -; mRNA.
DR EMBL; AF212303; AAF73376.1; -; mRNA.
DR EMBL; AY817669; AAV68046.1; -; Genomic_DNA.
DR EMBL; BX537431; CAD97673.1; ALT_INIT; mRNA.
DR EMBL; AL139341; CAI17224.1; -; Genomic_DNA.
DR EMBL; CH471066; EAW49601.1; -; Genomic_DNA.
DR EMBL; CH471066; EAW49602.1; -; Genomic_DNA.
DR EMBL; CH471066; EAW49603.1; -; Genomic_DNA.
DR EMBL; BC000127; AAH00127.1; -; mRNA.
DR RefSeq; NP_001177931.1; NM_001191002.1.
DR RefSeq; NP_001177932.1; NM_001191003.1.
DR RefSeq; NP_004823.1; NM_004832.2.
DR UniGene; Hs.190028; -.
DR PDB; 1EEM; X-ray; 2.00 A; A=1-241.
DR PDB; 3LFL; X-ray; 2.10 A; A/B/C=1-241.
DR PDB; 3VLN; X-ray; 1.70 A; A=1-241.
DR PDB; 4IS0; X-ray; 1.72 A; A=1-241.
DR PDBsum; 1EEM; -.
DR PDBsum; 3LFL; -.
DR PDBsum; 3VLN; -.
DR PDBsum; 4IS0; -.
DR ProteinModelPortal; P78417; -.
DR SMR; P78417; 3-241.
DR IntAct; P78417; 7.
DR MINT; MINT-1384709; -.
DR STRING; 9606.ENSP00000358727; -.
DR BindingDB; P78417; -.
DR ChEMBL; CHEMBL3174; -.
DR DrugBank; DB00143; Glutathione.
DR PhosphoSite; P78417; -.
DR DMDM; 6016173; -.
DR OGP; P78417; -.
DR UCD-2DPAGE; P78417; -.
DR PaxDb; P78417; -.
DR PeptideAtlas; P78417; -.
DR PRIDE; P78417; -.
DR Ensembl; ENST00000369710; ENSP00000358724; ENSG00000148834.
DR Ensembl; ENST00000369713; ENSP00000358727; ENSG00000148834.
DR Ensembl; ENST00000539281; ENSP00000441488; ENSG00000148834.
DR GeneID; 9446; -.
DR KEGG; hsa:9446; -.
DR UCSC; uc021pxs.1; human.
DR CTD; 9446; -.
DR GeneCards; GC10P106004; -.
DR HGNC; HGNC:13312; GSTO1.
DR HPA; HPA037604; -.
DR MIM; 605482; gene.
DR neXtProt; NX_P78417; -.
DR PharmGKB; PA133787054; -.
DR eggNOG; COG0625; -.
DR HOGENOM; HOG000006560; -.
DR HOVERGEN; HBG051853; -.
DR InParanoid; P78417; -.
DR KO; K00799; -.
DR OMA; QPEIKFS; -.
DR OrthoDB; EOG71CFNG; -.
DR PhylomeDB; P78417; -.
DR BioCyc; MetaCyc:HS07564-MONOMER; -.
DR Reactome; REACT_111217; Metabolism.
DR Reactome; REACT_116125; Disease.
DR ChiTaRS; GSTO1; human.
DR EvolutionaryTrace; P78417; -.
DR GeneWiki; GSTO1; -.
DR GenomeRNAi; 9446; -.
DR NextBio; 35384; -.
DR PRO; PR:P78417; -.
DR ArrayExpress; P78417; -.
DR Bgee; P78417; -.
DR CleanEx; HS_GSTO1; -.
DR Genevestigator; P78417; -.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0045174; F:glutathione dehydrogenase (ascorbate) activity; IDA:UniProtKB.
DR GO; GO:0004364; F:glutathione transferase activity; IDA:UniProtKB.
DR GO; GO:0050610; F:methylarsonate reductase activity; IEA:UniProtKB-EC.
DR GO; GO:0071243; P:cellular response to arsenic-containing substance; IDA:UniProtKB.
DR GO; GO:1901687; P:glutathione derivative biosynthetic process; TAS:Reactome.
DR GO; GO:0019852; P:L-ascorbic acid metabolic process; IDA:UniProtKB.
DR GO; GO:0060315; P:negative regulation of ryanodine-sensitive calcium-release channel activity; IDA:BHF-UCL.
DR GO; GO:0060316; P:positive regulation of ryanodine-sensitive calcium-release channel activity; IDA:BHF-UCL.
DR GO; GO:0014810; P:positive regulation of skeletal muscle contraction by regulation of release of sequestered calcium ion; IC:BHF-UCL.
DR GO; GO:0010881; P:regulation of cardiac muscle contraction by regulation of the release of sequestered calcium ion; IC:BHF-UCL.
DR GO; GO:0042178; P:xenobiotic catabolic 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; IPR005442; GST_omega.
DR InterPro; IPR012336; Thioredoxin-like_fold.
DR Pfam; PF00043; GST_C; 1.
DR Pfam; PF13417; GST_N_3; 1.
DR PRINTS; PR01625; GSTRNSFRASEO.
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; Alternative splicing; Complete proteome;
KW Cytoplasm; Direct protein sequencing; Oxidoreductase; Polymorphism;
KW Reference proteome; Transferase.
FT INIT_MET 1 1 Removed.
FT CHAIN 2 241 Glutathione S-transferase omega-1.
FT /FTId=PRO_0000185884.
FT DOMAIN 22 101 GST N-terminal.
FT DOMAIN 106 230 GST C-terminal.
FT REGION 85 86 Glutathione binding.
FT ACT_SITE 32 32 Nucleophile.
FT BINDING 59 59 Glutathione.
FT BINDING 72 72 Glutathione; via amide nitrogen and
FT carbonyl oxygen.
FT MOD_RES 2 2 N-acetylserine.
FT MOD_RES 57 57 N6-acetyllysine.
FT MOD_RES 143 143 N6-acetyllysine.
FT MOD_RES 148 148 N6-acetyllysine.
FT MOD_RES 152 152 N6-acetyllysine.
FT VAR_SEQ 1 28 Missing (in isoform 3).
FT /FTId=VSP_045819.
FT VAR_SEQ 123 155 Missing (in isoform 2).
FT /FTId=VSP_045820.
FT VARIANT 32 32 C -> Y (in dbSNP:rs45529437).
FT /FTId=VAR_061231.
FT VARIANT 86 86 S -> C (in dbSNP:rs11509436).
FT /FTId=VAR_029269.
FT VARIANT 140 140 A -> D (in allele GSTO1*C; no effect on
FT protein stability; dbSNP:rs4925).
FT /FTId=VAR_016811.
FT VARIANT 155 155 Missing (in allele GSTO1*B; decreased
FT protein stability).
FT /FTId=VAR_016813.
FT VARIANT 208 208 E -> K (in dbSNP:rs11509438).
FT /FTId=VAR_024484.
FT VARIANT 236 236 A -> V (in dbSNP:rs11509439).
FT /FTId=VAR_026583.
FT MUTAGEN 32 32 C->A: Loss of activity.
FT HELIX 4 6
FT STRAND 24 28
FT HELIX 33 45
FT STRAND 49 54
FT STRAND 56 58
FT HELIX 63 66
FT STRAND 74 76
FT STRAND 82 85
FT HELIX 86 96
FT HELIX 107 120
FT HELIX 123 131
FT HELIX 136 160
FT STRAND 162 164
FT STRAND 167 169
FT HELIX 172 184
FT TURN 185 188
FT HELIX 190 192
FT STRAND 193 195
FT HELIX 197 207
FT HELIX 210 215
FT HELIX 219 229
FT TURN 230 232
FT HELIX 236 238
SQ SEQUENCE 241 AA; 27566 MW; 9134ABA265F5C87E CRC64;
MSGESARSLG KGSAPPGPVP EGSIRIYSMR FCPFAERTRL VLKAKGIRHE VININLKNKP
EWFFKKNPFG LVPVLENSQG QLIYESAITC EYLDEAYPGK KLLPDDPYEK ACQKMILELF
SKVPSLVGSF IRSQNKEDYA GLKEEFRKEF TKLEEVLTNK KTTFFGGNSI SMIDYLIWPW
FERLEAMKLN ECVDHTPKLK LWMAAMKEDP TVSALLTSEK DWQGFLELYL QNSPEACDYG
L
//
MIM
605482
*RECORD*
*FIELD* NO
605482
*FIELD* TI
*605482 GLUTATHIONE S-TRANSFERASE, OMEGA-1; GSTO1
*FIELD* TX
DESCRIPTION
The glutathione S-transferases (GST; EC 2.5.1.18) are a family of
read moreenzymes responsible for the metabolism of a broad range of xenobiotics
and carcinogens (Mannervik, 1985). This enzyme catalyzes the reaction of
glutathione with a wide variety of organic compounds to form thioethers,
a reaction that is sometimes a first step in a detoxification process
leading to mercapturic acid formation.
Based on amino acid sequence similarities and antibody
cross-reactivities, 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 (134660), omega, and zeta
(603758). In addition, there is a class of microsomal GSTs (e.g.,
138330).
CLONING
By searching an EST database for homologies with GSTZ1 (603758), Board
et al. (2000) identified a cDNA encoding GSTO1, the first member of the
omega GST class. The deduced 241-amino acid protein has over 70%
identity with the rodent omega GST sequences. Of the previously defined
GST classes, the omega GSTS are most similar to the zeta class. The
omega class GSTs possess a 19- to 20-residue N-terminal extension, not
observed in other GSTs, that abuts the C terminus to form a novel
structural unit. Northern blot analysis revealed ubiquitous expression
of a 0.8-kb GSTO1 transcript, with highest expression in liver, skeletal
muscle, and heart, and lowest expression in brain, placenta, and lung.
Board et al. (2000) noted that the ubiquitous expression of GSTO1
contrasts with the tissue-specific expression typical of many GSTs.
Western blot analysis of cytosolic extracts and recombinant protein
showed that GSTO1 is expressed as a 31-kD protein in its monomeric form.
BIOCHEMICAL FEATURES
- Cystral Structure
Crystal structure analysis of GSTO1 by Board et al. (2000) demonstrated
that GSTO1 has an N-terminal thioredoxin-like domain consisting of a
central 4-stranded beta sheet flanked on one side by 2 alpha helices and
on the other by a 3-10 helix. The C terminus is composed of 7 alpha
helices and makes several H bonds with the N-terminal domain. GSTO1
forms a dimer and adopts the typical GST tertiary structure.
GENE FUNCTION
Functional analyses by Board et al. (2000) showed that GSTO1 lacks
activity with most GST substrates but exhibits glutathione-dependent
thiol transferase and dehydroascorbate reductase activity characteristic
of the glutaredoxins (e.g., GLRX, 600443). Whitbread et al. (2003)
stated that GSTO1 also reduces monomethylarsonic acid to
monomethylarsonous acid, which is the rate-limiting step in the
biotransformation of inorganic arsenic.
Kim et al. (2012) found that the Gsto1a and Gsto1b isoforms of
Drosophila Gsto1 had distinct physiologic activities. Gsto1b protected
flies against oxidative stress, whereas Gsto1a increased mitochondrial
ATPase synthase complex assembly and activity by glutathionylation of
the ATP synthase beta subunit (ATP5B; 102910). Overexpression of Gsto1a
partially reversed the phenotype of parkin (PARK2; 602544) mutant files,
including degeneration of dopaminergic neurons and muscle, cellular
tubulin (see 602529) accumulation, and endoplasmic reticulum stress. Kim
et al. (2012) concluded that Drosophila Gsto1 plays a protective role in
parkin mutants by regulating mitochondrial ATP synthase activity.
GENE STRUCTURE
Whitbread et al. (2003) determined that the GSTO1 gene contains 6 exons
and spans 12.5 kb.
MAPPING
By FISH and somatic cell hybrid analyses, Whitbread et al. (2003) mapped
the GSTO1 gene to chromosome 10q24-q25, about 7.5-kb upstream of the
GSTO2 gene (612314). Whitbread et al. (2003) also identified an apparent
GSTO1-related pseudogene on chromosome 3.
MOLECULAR GENETICS
By database analysis, Whitbread et al. (2003) identified several
putative polymorphisms in the coding region of GSTO1 and confirmed 11 of
these by reexamining the cDNA sequences. They identified 2 of the
polymorphisms in their study population (100 European Australians, 62
Bantu Africans, and 100 Southern Chinese). One was a 419C-T transition
resulting in an ala140-to-asp (A140D) substitution; the frequency of the
D140 allele was notably different between the groups, being highest in
Australians and lowest in Africans. The other was a rare splicing
polymorphism at IVS4, resulting in deletion of glu155 (E155del). Only 1
Chinese individual was homozygous for the deletion. In vitro assays
showed that the A140D substitution had no effect on the thioltransferase
and GSH-conjugation activity of GSTO1, whereas E155del polymorphism
resulted in significantly higher GSTO1 activity in both assays. The
E155del variant also showed lower thermal stability than the other
variants.
ANIMAL MODEL
Kim et al. (2012) found that knockdown of Gsto1 in Drosophila resulted
in no obvious defects in adult morphology. However, mutant flies were
sensitive to paraquat, an oxidative stress inducer. Double mutation of
parkin and Gsto1a accentuated the phenotype of parkin mutant flies, with
dramatically enhanced degeneration of indirect flight muscles.
*FIELD* RF
1. Board, P. G.; Coggan, M.; Chelvanayagam, G.; Easteal, S.; Jermiin,
L. S.; Schulte, G. K.; Danley, D. E.; Hoth, L. R.; Griffor, M. C.;
Kamath, A. V.; Rosner, M. H.; Chrunyk, B. A.; Perregaux, D. E.; Gabel,
C. A.; Geoghegan, K. F.; Pandit, J.: Identification, characterization,
and crystal structure of the omega class glutathione transferases. J.
Biol. Chem. 275: 24798-24806, 2000.
2. Kim, K.; Kim, S.-H.; Kim, J.; Kim, H.; Yim, J.: Glutathione S-transferase
omega 1 activity is sufficient to suppress neurodegeneration in a
Drosophila model of Parkinson disease. J. Biol. Chem. 287: 6628-6641,
2012.
3. Mannervik, B.: The isozymes of glutathione transferase. Adv.
Enzym. Relat. Areas Molec. Biol. 57: 357-417, 1985.
4. Whitbread, A. K.; Tetlow, N.; Eyre, H. J.; Sutherland, G. R.; Board,
P. G.: Characterization of the human omega class glutathione transferase
genes and associated polymorphisms. Pharmacogenetics 13: 131-144,
2003.
*FIELD* CN
Patricia A. Hartz - updated: 10/19/2012
Patricia A. Hartz - updated: 9/24/2008
George E. Tiller - updated: 1/10/2006
*FIELD* CD
Paul J. Converse: 12/20/2000
*FIELD* ED
mgross: 11/09/2012
terry: 10/19/2012
carol: 9/24/2008
terry: 9/24/2008
carol: 9/19/2008
wwang: 2/15/2006
terry: 1/10/2006
mgross: 12/20/2000
*RECORD*
*FIELD* NO
605482
*FIELD* TI
*605482 GLUTATHIONE S-TRANSFERASE, OMEGA-1; GSTO1
*FIELD* TX
DESCRIPTION
The glutathione S-transferases (GST; EC 2.5.1.18) are a family of
read moreenzymes responsible for the metabolism of a broad range of xenobiotics
and carcinogens (Mannervik, 1985). This enzyme catalyzes the reaction of
glutathione with a wide variety of organic compounds to form thioethers,
a reaction that is sometimes a first step in a detoxification process
leading to mercapturic acid formation.
Based on amino acid sequence similarities and antibody
cross-reactivities, 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 (134660), omega, and zeta
(603758). In addition, there is a class of microsomal GSTs (e.g.,
138330).
CLONING
By searching an EST database for homologies with GSTZ1 (603758), Board
et al. (2000) identified a cDNA encoding GSTO1, the first member of the
omega GST class. The deduced 241-amino acid protein has over 70%
identity with the rodent omega GST sequences. Of the previously defined
GST classes, the omega GSTS are most similar to the zeta class. The
omega class GSTs possess a 19- to 20-residue N-terminal extension, not
observed in other GSTs, that abuts the C terminus to form a novel
structural unit. Northern blot analysis revealed ubiquitous expression
of a 0.8-kb GSTO1 transcript, with highest expression in liver, skeletal
muscle, and heart, and lowest expression in brain, placenta, and lung.
Board et al. (2000) noted that the ubiquitous expression of GSTO1
contrasts with the tissue-specific expression typical of many GSTs.
Western blot analysis of cytosolic extracts and recombinant protein
showed that GSTO1 is expressed as a 31-kD protein in its monomeric form.
BIOCHEMICAL FEATURES
- Cystral Structure
Crystal structure analysis of GSTO1 by Board et al. (2000) demonstrated
that GSTO1 has an N-terminal thioredoxin-like domain consisting of a
central 4-stranded beta sheet flanked on one side by 2 alpha helices and
on the other by a 3-10 helix. The C terminus is composed of 7 alpha
helices and makes several H bonds with the N-terminal domain. GSTO1
forms a dimer and adopts the typical GST tertiary structure.
GENE FUNCTION
Functional analyses by Board et al. (2000) showed that GSTO1 lacks
activity with most GST substrates but exhibits glutathione-dependent
thiol transferase and dehydroascorbate reductase activity characteristic
of the glutaredoxins (e.g., GLRX, 600443). Whitbread et al. (2003)
stated that GSTO1 also reduces monomethylarsonic acid to
monomethylarsonous acid, which is the rate-limiting step in the
biotransformation of inorganic arsenic.
Kim et al. (2012) found that the Gsto1a and Gsto1b isoforms of
Drosophila Gsto1 had distinct physiologic activities. Gsto1b protected
flies against oxidative stress, whereas Gsto1a increased mitochondrial
ATPase synthase complex assembly and activity by glutathionylation of
the ATP synthase beta subunit (ATP5B; 102910). Overexpression of Gsto1a
partially reversed the phenotype of parkin (PARK2; 602544) mutant files,
including degeneration of dopaminergic neurons and muscle, cellular
tubulin (see 602529) accumulation, and endoplasmic reticulum stress. Kim
et al. (2012) concluded that Drosophila Gsto1 plays a protective role in
parkin mutants by regulating mitochondrial ATP synthase activity.
GENE STRUCTURE
Whitbread et al. (2003) determined that the GSTO1 gene contains 6 exons
and spans 12.5 kb.
MAPPING
By FISH and somatic cell hybrid analyses, Whitbread et al. (2003) mapped
the GSTO1 gene to chromosome 10q24-q25, about 7.5-kb upstream of the
GSTO2 gene (612314). Whitbread et al. (2003) also identified an apparent
GSTO1-related pseudogene on chromosome 3.
MOLECULAR GENETICS
By database analysis, Whitbread et al. (2003) identified several
putative polymorphisms in the coding region of GSTO1 and confirmed 11 of
these by reexamining the cDNA sequences. They identified 2 of the
polymorphisms in their study population (100 European Australians, 62
Bantu Africans, and 100 Southern Chinese). One was a 419C-T transition
resulting in an ala140-to-asp (A140D) substitution; the frequency of the
D140 allele was notably different between the groups, being highest in
Australians and lowest in Africans. The other was a rare splicing
polymorphism at IVS4, resulting in deletion of glu155 (E155del). Only 1
Chinese individual was homozygous for the deletion. In vitro assays
showed that the A140D substitution had no effect on the thioltransferase
and GSH-conjugation activity of GSTO1, whereas E155del polymorphism
resulted in significantly higher GSTO1 activity in both assays. The
E155del variant also showed lower thermal stability than the other
variants.
ANIMAL MODEL
Kim et al. (2012) found that knockdown of Gsto1 in Drosophila resulted
in no obvious defects in adult morphology. However, mutant flies were
sensitive to paraquat, an oxidative stress inducer. Double mutation of
parkin and Gsto1a accentuated the phenotype of parkin mutant flies, with
dramatically enhanced degeneration of indirect flight muscles.
*FIELD* RF
1. Board, P. G.; Coggan, M.; Chelvanayagam, G.; Easteal, S.; Jermiin,
L. S.; Schulte, G. K.; Danley, D. E.; Hoth, L. R.; Griffor, M. C.;
Kamath, A. V.; Rosner, M. H.; Chrunyk, B. A.; Perregaux, D. E.; Gabel,
C. A.; Geoghegan, K. F.; Pandit, J.: Identification, characterization,
and crystal structure of the omega class glutathione transferases. J.
Biol. Chem. 275: 24798-24806, 2000.
2. Kim, K.; Kim, S.-H.; Kim, J.; Kim, H.; Yim, J.: Glutathione S-transferase
omega 1 activity is sufficient to suppress neurodegeneration in a
Drosophila model of Parkinson disease. J. Biol. Chem. 287: 6628-6641,
2012.
3. Mannervik, B.: The isozymes of glutathione transferase. Adv.
Enzym. Relat. Areas Molec. Biol. 57: 357-417, 1985.
4. Whitbread, A. K.; Tetlow, N.; Eyre, H. J.; Sutherland, G. R.; Board,
P. G.: Characterization of the human omega class glutathione transferase
genes and associated polymorphisms. Pharmacogenetics 13: 131-144,
2003.
*FIELD* CN
Patricia A. Hartz - updated: 10/19/2012
Patricia A. Hartz - updated: 9/24/2008
George E. Tiller - updated: 1/10/2006
*FIELD* CD
Paul J. Converse: 12/20/2000
*FIELD* ED
mgross: 11/09/2012
terry: 10/19/2012
carol: 9/24/2008
terry: 9/24/2008
carol: 9/19/2008
wwang: 2/15/2006
terry: 1/10/2006
mgross: 12/20/2000