P78417 (GSTO1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Glutathione S-transferase omega-1
Short name=GSTO-1
EC=2.5.1.18

Alternative name(s):
Glutathione S-transferase omega 1-1
Short name=GSTO 1-1
Glutathione-dependent dehydroascorbate reductase
EC=1.8.5.1
Monomethylarsonic acid reductase
Short name=MMA(V) reductase
EC=1.20.4.2
S-(Phenacyl)glutathione reductase
Short name=SPG-R

Gene names

Name:	GSTO1
Synonyms:	GSTTLP28

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	241 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Exhibits glutathione-dependent thiol transferase and dehydroascorbate reductase activities. Has S-(phenacyl)glutathione reductase activity. Has also glutathione S-transferase activity. Participates in the biotransformation of inorganic arsenic and reduces monomethylarsonic acid (MMA) and dimethylarsonic acid. Ref.2 Ref.9 Ref.10 Ref.11 Ref.14
Catalytic activity	RX + glutathione = HX + R-S-glutathione. Ref.2 Ref.9 Ref.10 Ref.11 Ref.14 2 glutathione + dehydroascorbate = glutathione disulfide + ascorbate. Ref.2 Ref.9 Ref.10 Ref.11 Ref.14 Methylarsonate + 2 glutathione = methylarsonite + glutathione disulfide + H2O. Ref.2 Ref.9 Ref.10 Ref.11 Ref.14
Enzyme regulation	Monomethylarsonic acid reductase activity is competitively inhibited by 1-chloro 2,4-dinitrobenzene (CDNB) and by deoxycholate.
Subunit structure	Homodimer. Ref.2 Ref.14
Subcellular location	Cytoplasm › cytosol Ref.9.
Tissue specificity	Ubiquitous. Highest expression in liver, pancreas, skeletal muscle, spleen, thymus, colon, blood leukocyte and heart. Lowest expression in brain, placenta and lung. Ref.2
Sequence similarities	Belongs to the GST superfamily. Omega family. Contains 1 GST C-terminal domain. Contains 1 GST N-terminal domain.
Biophysicochemical properties	pH dependence: Optimum pH is 8. Ref.9 Ref.10
Sequence caution	The sequence CAD97673.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.

Ontologies

Keywords
Cellular component	Cytoplasm
Coding sequence diversity	Alternative splicing Polymorphism
Molecular function	Oxidoreductase Transferase
PTM	Acetylation
Technical term	3D-structure Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	L-ascorbic acid metabolic process Inferred from direct assay Ref.9. Source: UniProtKB cellular response to arsenic-containing substance Inferred from direct assay Ref.9. Source: UniProtKB negative regulation of ryanodine-sensitive calcium-release channel activity Inferred from direct assay PubMed 11035031. Source: BHF-UCL positive regulation of ryanodine-sensitive calcium-release channel activity Inferred from direct assay PubMed 11035031. Source: BHF-UCL positive regulation of skeletal muscle contraction by regulation of release of sequestered calcium ion Inferred by curator PubMed 11035031. Source: BHF-UCL regulation of cardiac muscle contraction by regulation of the release of sequestered calcium ion Inferred by curator PubMed 11035031. Source: BHF-UCL xenobiotic catabolic process Inferred from direct assay Ref.3. Source: UniProtKB
Cellular_component	cytosol Traceable author statement. Source: Reactome
Molecular_function	glutathione dehydrogenase (ascorbate) activity Inferred from direct assay Ref.9. Source: UniProtKB glutathione transferase activity Inferred from direct assay Ref.9. Source: UniProtKB methylarsonate reductase activity Inferred from electronic annotation. Source: EC
Complete GO annotation...

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: P78417-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

Isoform 2 (identifier: P78417-2)

The sequence of this isoform differs from the canonical sequence as follows:
     123-155: Missing.

Isoform 3 (identifier: P78417-3)

The sequence of this isoform differs from the canonical sequence as follows:
     1-28: Missing.

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 241

241

Glutathione S-transferase omega-1

PRO_0000185884

Regions

Domain

22 – 101

80

GST N-terminal

Domain

106 – 230

125

GST C-terminal

Region

85 – 86

2

Glutathione binding

Sites

Active site

32

1

Nucleophile Ref.2

Binding site

59

1

Glutathione

Binding site

72

1

Glutathione; via amide nitrogen and carbonyl oxygen

Amino acid modifications

Modified residue

57

1

N6-acetyllysine Ref.12

Modified residue

143

1

N6-acetyllysine Ref.12

Modified residue

148

1

N6-acetyllysine Ref.12

Modified residue

152

1

N6-acetyllysine Ref.12

Natural variations

Alternative sequence

1 – 28

28

Missing in isoform 3.

VSP_045819

Alternative sequence

123 – 155

33

Missing in isoform 2.

VSP_045820

Natural variant

32

1

C → Y.
Corresponds to variant rs45529437 [ dbSNP | Ensembl ].

VAR_061231

Natural variant

86

1

S → C.
Corresponds to variant rs11509436 [ dbSNP | Ensembl ].

VAR_029269

Natural variant

140

1

A → D in allele GSTO1*C; no effect on protein stability. Ref.3 Ref.14 Ref.15
Corresponds to variant rs4925 [ dbSNP | Ensembl ].

VAR_016811

Natural variant

155

1

Missing in allele GSTO1*B; decreased protein stability. Ref.3 Ref.14 Ref.15

VAR_016813

Natural variant

208

1

E → K. Ref.3
Corresponds to variant rs11509438 [ dbSNP | Ensembl ].

VAR_024484

Natural variant

236

1

A → V. Ref.3
Corresponds to variant rs11509439 [ dbSNP | Ensembl ].

VAR_026583

Experimental info

Mutagenesis

32

1

C → A: Loss of activity. Ref.10

Secondary structure

1

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241

Helix Strand Turn

Details...

Helix

4 – 6

3

Beta strand

24 – 28

5

Helix

33 – 45

13

Beta strand

49 – 54

6

Beta strand

56 – 58

3

Helix

63 – 66

4

Beta strand

74 – 76

3

Beta strand

82 – 85

4

Helix

86 – 96

11

Helix

107 – 120

14

Helix

123 – 131

9

Helix

136 – 160

25

Beta strand

162 – 164

3

Beta strand

167 – 169

3

Helix

172 – 184

13

Turn

185 – 188

4

Helix

190 – 192

3

Beta strand

193 – 195

3

Helix

197 – 207

11

Helix

210 – 215

6

Helix

219 – 229

11

Turn

230 – 232

3

Helix

236 – 238

3

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified January 1, 1998. Version 2. Checksum: 9134ABA265F5C87E	FASTA	241	27,566
	10 20 30 40 50 60 MSGESARSLG KGSAPPGPVP EGSIRIYSMR FCPFAERTRL VLKAKGIRHE VININLKNKP 70 80 90 100 110 120 EWFFKKNPFG LVPVLENSQG QLIYESAITC EYLDEAYPGK KLLPDDPYEK ACQKMILELF 130 140 150 160 170 180 SKVPSLVGSF IRSQNKEDYA GLKEEFRKEF TKLEEVLTNK KTTFFGGNSI SMIDYLIWPW 190 200 210 220 230 240 FERLEAMKLN ECVDHTPKLK LWMAAMKEDP TVSALLTSEK DWQGFLELYL QNSPEACDYG L
	Isoform 2 [UniParc]. Checksum: F00CDE200E2A1738	FASTA	208	23,709
	10 20 30 40 50 60 MSGESARSLG KGSAPPGPVP EGSIRIYSMR FCPFAERTRL VLKAKGIRHE VININLKNKP 70 80 90 100 110 120 EWFFKKNPFG LVPVLENSQG QLIYESAITC EYLDEAYPGK KLLPDDPYEK ACQKMILELF 130 140 150 160 170 180 SKVLTNKKTT FFGGNSISMI DYLIWPWFER LEAMKLNECV DHTPKLKLWM AAMKEDPTVS 190 200 ALLTSEKDWQ GFLELYLQNS PEACDYGL
	Isoform 3 [UniParc]. Checksum: C3F8EBA348399628	FASTA	213	24,796
	10 20 30 40 50 60 MRFCPFAERT RLVLKAKGIR HEVININLKN KPEWFFKKNP FGLVPVLENS QGQLIYESAI 70 80 90 100 110 120 TCEYLDEAYP GKKLLPDDPY EKACQKMILE LFSKVPSLVG SFIRSQNKED YAGLKEEFRK 130 140 150 160 170 180 EFTKLEEVLT NKKTTFFGGN SISMIDYLIW PWFERLEAMK LNECVDHTPK LKLWMAAMKE 190 200 210 DPTVSALLTS EKDWQGFLEL YLQNSPEACD YGL

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Cloning of the human homolog to a mouse protein, differentially expressed in lymphoma cells with different susceptibility to radiation induced apoptosis." Kodym R., Story M.D. Submitted (FEB-1997) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). Tissue: Placenta.
[2]	"Identification, characterization, and crystal structure of the Omega class glutathione transferases." 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. J. Biol. Chem. 275:24798-24806(2000) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) IN COMPLEX WITH GLUTATHIONE, FUNCTION, CATALYTIC ACTIVITY, ACTIVE SITE, SUBUNIT, TISSUE SPECIFICITY. Tissue: Fetus.
[3]	"Genetic variation in genes associated with arsenic metabolism: glutathione S-transferase omega 1-1 and purine nucleoside phosphorylase polymorphisms in European and indigenous Americans." Yu L., Kalla K., Guthrie E., Vidrine A., Klimecki W.T. Environ. Health Perspect. 111:1421-1427(2003) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS ASP-140; GLU-155 DEL; LYS-208 AND VAL-236.
[4]	"The full-ORF clone resource of the German cDNA consortium." Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U., Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D., Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A., Wiemann S., Schupp I. BMC Genomics 8:399-399(2007) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). Tissue: Uterus.
[5]	"The DNA sequence and comparative analysis of human chromosome 10." Deloukas P., Earthrowl M.E., Grafham D.V., Rubenfield M., French L., Steward C.A., Sims S.K., Jones M.C., Searle S., Scott C., Howe K., Hunt S.E., Andrews T.D., Gilbert J.G.R., Swarbreck D., Ashurst J.L., Taylor A., Battles J. , Bird C.P., Ainscough R., Almeida J.P., Ashwell R.I.S., Ambrose K.D., Babbage A.K., Bagguley C.L., Bailey J., Banerjee R., Bates K., Beasley H., Bray-Allen S., Brown A.J., Brown J.Y., Burford D.C., Burrill W., Burton J., Cahill P., Camire D., Carter N.P., Chapman J.C., Clark S.Y., Clarke G., Clee C.M., Clegg S., Corby N., Coulson A., Dhami P., Dutta I., Dunn M., Faulkner L., Frankish A., Frankland J.A., Garner P., Garnett J., Gribble S., Griffiths C., Grocock R., Gustafson E., Hammond S., Harley J.L., Hart E., Heath P.D., Ho T.P., Hopkins B., Horne J., Howden P.J., Huckle E., Hynds C., Johnson C., Johnson D., Kana A., Kay M., Kimberley A.M., Kershaw J.K., Kokkinaki M., Laird G.K., Lawlor S., Lee H.M., Leongamornlert D.A., Laird G., Lloyd C., Lloyd D.M., Loveland J., Lovell J., McLaren S., McLay K.E., McMurray A., Mashreghi-Mohammadi M., Matthews L., Milne S., Nickerson T., Nguyen M., Overton-Larty E., Palmer S.A., Pearce A.V., Peck A.I., Pelan S., Phillimore B., Porter K., Rice C.M., Rogosin A., Ross M.T., Sarafidou T., Sehra H.K., Shownkeen R., Skuce C.D., Smith M., Standring L., Sycamore N., Tester J., Thorpe A., Torcasso W., Tracey A., Tromans A., Tsolas J., Wall M., Walsh J., Wang H., Weinstock K., West A.P., Willey D.L., Whitehead S.L., Wilming L., Wray P.W., Young L., Chen Y., Lovering R.C., Moschonas N.K., Siebert R., Fechtel K., Bentley D., Durbin R.M., Hubbard T., Doucette-Stamm L., Beck S., Smith D.R., Rogers J. Nature 429:375-381(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]	Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[7]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). Tissue: Eye.
[8]	"Human ERp29: isolation, primary structural characterisation and two-dimensional gel mapping." Hubbard M.J., McHugh N.J. Electrophoresis 21:3785-3796(2000) [PubMed] [Europe PMC] [Abstract] Cited for: PROTEIN SEQUENCE OF 12-21; 58-65; 133-139 AND 149-156, MASS SPECTROMETRY. Tissue: Liver.
[9]	"Human monomethylarsonic acid (MMA(V)) reductase is a member of the glutathione-S-transferase superfamily." Zakharyan R.A., Sampayo-Reyes A., Healy S.M., Tsaprailis G., Board P.G., Liebler D.C., Aposhian H.V. Chem. Res. Toxicol. 14:1051-1057(2001) [PubMed] [Europe PMC] [Abstract] Cited for: PARTIAL PROTEIN SEQUENCE, FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, SUBCELLULAR LOCATION, MASS SPECTROMETRY. Tissue: Liver.
[10]	"Glutathione transferase omega 1 catalyzes the reduction of S-(phenacyl)glutathiones to acetophenones." Board P.G., Anders M.W. Chem. Res. Toxicol. 20:149-154(2007) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, MUTAGENESIS OF CYS-32, BIOPHYSICOCHEMICAL PROPERTIES, CATALYTIC ACTIVITY.
[11]	"S-(4-Nitrophenacyl)glutathione is a specific substrate for glutathione transferase omega 1-1." Board P.G., Coggan M., Cappello J., Zhou H., Oakley A.J., Anders M.W. Anal. Biochem. 374:25-30(2008) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, CATALYTIC ACTIVITY.
[12]	"Lysine acetylation targets protein complexes and co-regulates major cellular functions." Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T.C., Olsen J.V., Mann M. Science 325:834-840(2009) [PubMed] [Europe PMC] [Abstract] Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-57; LYS-143; LYS-148 AND LYS-152, MASS SPECTROMETRY.
[13]	"Initial characterization of the human central proteome." Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J. BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[14]	"Novel folding and stability defects cause a deficiency of human glutathione transferase omega 1." Zhou H., Brock J., Casarotto M.G., Oakley A.J., Board P.G. J. Biol. Chem. 286:4271-4279(2011) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS) OF VARIANT GLU-155 DEL, FUNCTION, CATALYTIC ACTIVITY, SUBUNIT, CHARACTERIZATION OF VARIANTS ASP-140 AND GLU-155 DEL.
[15]	"Characterization of the human Omega class glutathione transferase genes and associated polymorphisms." Whitbread A.K., Tetlow N., Eyre H.J., Sutherland G.R., Board P.G. Pharmacogenetics 13:131-144(2003) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS ASP-140 AND GLU-155 DEL.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

U90313 mRNA. Translation: AAB70109.1.
AF212303 mRNA. Translation: AAF73376.1.
AY817669 Genomic DNA. Translation: AAV68046.1.
BX537431 mRNA. Translation: CAD97673.1. Different initiation.
AL139341 Genomic DNA. Translation: CAI17224.1.
CH471066 Genomic DNA. Translation: EAW49601.1.
CH471066 Genomic DNA. Translation: EAW49602.1.
CH471066 Genomic DNA. Translation: EAW49603.1.
BC000127 mRNA. Translation: AAH00127.1.

IPI

IPI00019755.
IPI00513927.
IPI00642936.

RefSeq

NP_001177931.1. NM_001191002.1.
NP_001177932.1. NM_001191003.1.
NP_004823.1. NM_004832.2.

UniGene

Hs.190028.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1EEM	X-ray	2.00	A	1-241	[»]
3LFL	X-ray	2.10	A/B/C	1-241	[»]
3VLN	X-ray	1.70	A	1-241	[»]

ProteinModelPortal

P78417.

ModBase

Search...

Protein-protein interaction databases

IntAct

P78417. 7 interactions.

MINT

MINT-1384709.

STRING

9606.ENSP00000358727.

PTM databases

PhosphoSite

P78417.

Polymorphism databases

DMDM

6016173.

2D gel databases

OGP

P78417.

UCD-2DPAGE

P78417.

Proteomic databases

PaxDb

P78417.

PeptideAtlas

P78417.

PRIDE

P78417.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000369710; ENSP00000358724; ENSG00000148834.
ENST00000369713; ENSP00000358727; ENSG00000148834.
ENST00000539281; ENSP00000441488; ENSG00000148834.

GeneID

9446.

KEGG

hsa:9446.

UCSC

uc001kya.3. human.

Organism-specific databases

CTD

9446.

GeneCards

GC10P106004.

HGNC

HGNC:13312. GSTO1.

HPA

HPA037604.

MIM

605482. gene.

neXtProt

NX_P78417.

PharmGKB

PA133787054.

GenAtlas

Search...

Phylogenomic databases

eggNOG

COG0625.

HOGENOM

HOG000006560.

HOVERGEN

HBG051853.

InParanoid

P78417.

KO

K00799.

OMA

PADPYEK.

OrthoDB

EOG43TZW5.

PhylomeDB

P78417.

Enzyme and pathway databases

BioCyc

MetaCyc:HS07564-MONOMER.

Reactome

REACT_111217. Metabolism.

Gene expression databases

ArrayExpress

P78417.

Bgee

P78417.

CleanEx

HS_GSTO1.

Genevestigator

P78417.

GermOnline

ENSG00000148834. Homo sapiens.

Family and domain databases

Gene3D

1.20.1050.10. 1 hit.
3.40.30.10. 1 hit.

InterPro

IPR010987. Glutathione-S-Trfase_C-like.
IPR004045. Glutathione_S-Trfase_N.
IPR017933. Glutathione_S_Trfase/Cl_chnl_C.
IPR004046. GST_C.
IPR005442. GST_omega.
IPR012336. Thioredoxin-like_fold.
[Graphical view]

Pfam

PF00043. GST_C. 1 hit.
[Graphical view]

PRINTS

PR01625. GSTRNSFRASEO.

SUPFAM

SSF47616. GST_C_like. 1 hit.
SSF52833. Thiordxn-like_fd. 1 hit.

PROSITE

PS50405. GST_CTER. 1 hit.
PS50404. GST_NTER. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

BindingDB

P78417.

ChEMBL

CHEMBL3174.

ChiTaRS

GSTO1. human.

DrugBank

DB00143. Glutathione.

EvolutionaryTrace

P78417.

GenomeRNAi

9446.

NextBio

35384.

SOURCE

Search...

Entry information

Entry name

GSTO1_HUMAN

Accession

Primary (citable) accession number: P78417
Secondary accession number(s): D3DRA3 , F5H7H0, Q5TA03, Q7Z3T2

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 15, 1999
Last sequence update:	January 1, 1998
Last modified:	May 1, 2013
This is version 138 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.