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P08263 (GSTA1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 162. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Glutathione S-transferase A1

EC=2.5.1.18
Alternative name(s):
GST HA subunit 1
GST class-alpha member 1
GST-epsilon
GSTA1-1
GTH1
Gene names
Name:GSTA1
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length222 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Conjugation of reduced glutathione to a wide number of exogenous and endogenous hydrophobic electrophiles. Ref.22

Catalytic activity

RX + glutathione = HX + R-S-glutathione. Ref.22

Subunit structure

Homodimer or heterodimer of GSTA1 and GSTA2. Ref.15 Ref.16 Ref.17 Ref.20

Subcellular location

Cytoplasm.

Tissue specificity

Liver.

Domain

The C-terminal domain may form a component of the hydrophobic substrate-binding site, but in contrast appears not to be directly involved in GSH binding and is not absolutely essential for catalytic activity.

Sequence similarities

Belongs to the GST superfamily. Alpha family.

Contains 1 GST C-terminal domain.

Contains 1 GST N-terminal domain.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 222222Glutathione S-transferase A1
PRO_0000423203
Initiator methionine11Removed; alternate Ref.12
Chain2 – 222221Glutathione S-transferase A1, N-terminally processed
PRO_0000185783

Regions

Domain3 – 8381GST N-terminal
Domain85 – 207123GST C-terminal
Region54 – 552Glutathione binding
Region67 – 682Glutathione binding

Sites

Binding site91Glutathione
Binding site451Glutathione

Amino acid modifications

Modified residue11N-acetylmethionine By similarity

Natural variations

Natural variant191T → I.
Corresponds to variant rs1051578 [ dbSNP | Ensembl ].
VAR_033978
Natural variant1131P → Q.
Corresponds to variant rs1051745 [ dbSNP | Ensembl ].
VAR_049482
Natural variant1171K → Q.
Corresponds to variant rs1051757 [ dbSNP | Ensembl ].
VAR_049483

Experimental info

Mutagenesis711I → A or V: No significant effect on enzyme activity. Reduces protein stability. Ref.22
Mutagenesis2161A → H: Confers ability to hydrolyze S-glutathionyl benzoate to glutathione and benzoic acid. Ref.18
Sequence conflict181S → C in AAA36174. Ref.3
Sequence conflict511M → T in AAT06769. Ref.7
Sequence conflict56 – 583PMV → AML in AAA36174. Ref.3
Sequence conflict2121S → L AA sequence Ref.13
Sequence conflict2161A → S AA sequence Ref.12

Secondary structure

................................. 222
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
P08263 [UniParc].

Last modified January 23, 2007. Version 3.
Checksum: C8B6786DCD761350

FASTA22225,631
        10         20         30         40         50         60 
MAEKPKLHYF NARGRMESTR WLLAAAGVEF EEKFIKSAED LDKLRNDGYL MFQQVPMVEI 

        70         80         90        100        110        120 
DGMKLVQTRA ILNYIASKYN LYGKDIKERA LIDMYIEGIA DLGEMILLLP VCPPEEKDAK 

       130        140        150        160        170        180 
LALIKEKIKN RYFPAFEKVL KSHGQDYLVG NKLSRADIHL VELLYYVEEL DSSLISSFPL 

       190        200        210        220 
LKALKTRISN LPTVKKFLQP GSPRKPPMDE KSLEEARKIF RF 

« Hide

References

« Hide 'large scale' references
[1]"Human liver glutathione S-transferases: complete primary sequence of an Ha subunit cDNA."
Tu C.-P.D., Qian B.
Biochem. Biophys. Res. Commun. 141:229-237(1986) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]"The basic glutathione S-transferases from human livers are products of separate genes."
Rhoads D.M., Zarlengo R.P., Tu C.-P.D.
Biochem. Biophys. Res. Commun. 145:474-481(1987) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[3]"Nucleotide sequence of the human liver glutathione S-transferase subunit 1 cDNA."
Tu C.-P.D., Qian B.
Biochem. Soc. Trans. 15:734-736(1987) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
Tissue: Liver.
[4]"Isolation of a cDNA clone and localization of human glutathione S-transferase 2 genes to chromosome band 6p12."
Board P.G., Webb G.C.
Proc. Natl. Acad. Sci. U.S.A. 84:2377-2381(1987) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[5]"Isolation and characterization of a human glutathione S-transferase Ha1 subunit gene."
Rozen F., Nguyen T., Pickett C.B.
Arch. Biochem. Biophys. 292:589-593(1992) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[6]"Heterologous expression of recombinant human glutathione transferase A1-1 from a hepatoma cell line."
Stenberg G., Bjornestedt R., Mannervik B.
Protein Expr. Purif. 3:80-84(1992) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[7]Chen P., Zhang C., Xie D., Wu Y., Han L., Chen L.
Submitted (JAN-2004) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
Tissue: Liver.
[8]"The DNA sequence and analysis of human chromosome 6."
Mungall A.J., Palmer S.A., Sims S.K., Edwards C.A., Ashurst J.L., Wilming L., Jones M.C., Horton R., Hunt S.E., Scott C.E., Gilbert J.G.R., Clamp M.E., Bethel G., Milne S., Ainscough R., Almeida J.P., Ambrose K.D., Andrews T.D. expand/collapse author list , Ashwell R.I.S., Babbage A.K., Bagguley C.L., Bailey J., Banerjee R., Barker D.J., Barlow K.F., Bates K., Beare D.M., Beasley H., Beasley O., Bird C.P., Blakey S.E., Bray-Allen S., Brook J., Brown A.J., Brown J.Y., Burford D.C., Burrill W., Burton J., Carder C., Carter N.P., Chapman J.C., Clark S.Y., Clark G., Clee C.M., Clegg S., Cobley V., Collier R.E., Collins J.E., Colman L.K., Corby N.R., Coville G.J., Culley K.M., Dhami P., Davies J., Dunn M., Earthrowl M.E., Ellington A.E., Evans K.A., Faulkner L., Francis M.D., Frankish A., Frankland J., French L., Garner P., Garnett J., Ghori M.J., Gilby L.M., Gillson C.J., Glithero R.J., Grafham D.V., Grant M., Gribble S., Griffiths C., Griffiths M.N.D., Hall R., Halls K.S., Hammond S., Harley J.L., Hart E.A., Heath P.D., Heathcott R., Holmes S.J., Howden P.J., Howe K.L., Howell G.R., Huckle E., Humphray S.J., Humphries M.D., Hunt A.R., Johnson C.M., Joy A.A., Kay M., Keenan S.J., Kimberley A.M., King A., Laird G.K., Langford C., Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C.R., Lloyd D.M., Loveland J.E., Lovell J., Martin S., Mashreghi-Mohammadi M., Maslen G.L., Matthews L., McCann O.T., McLaren S.J., McLay K., McMurray A., Moore M.J.F., Mullikin J.C., Niblett D., Nickerson T., Novik K.L., Oliver K., Overton-Larty E.K., Parker A., Patel R., Pearce A.V., Peck A.I., Phillimore B.J.C.T., Phillips S., Plumb R.W., Porter K.M., Ramsey Y., Ranby S.A., Rice C.M., Ross M.T., Searle S.M., Sehra H.K., Sheridan E., Skuce C.D., Smith S., Smith M., Spraggon L., Squares S.L., Steward C.A., Sycamore N., Tamlyn-Hall G., Tester J., Theaker A.J., Thomas D.W., Thorpe A., Tracey A., Tromans A., Tubby B., Wall M., Wallis J.M., West A.P., White S.S., Whitehead S.L., Whittaker H., Wild A., Willey D.J., Wilmer T.E., Wood J.M., Wray P.W., Wyatt J.C., Young L., Younger R.M., Bentley D.R., Coulson A., Durbin R.M., Hubbard T., Sulston J.E., Dunham I., Rogers J., Beck S.
Nature 425:805-811(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[9]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. expand/collapse author list , 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 (JUL-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[10]"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].
Tissue: Brain.
[11]"Human glutathione S-transferases. The Ha multigene family encodes products of different but overlapping substrate specificities."
Chow N.W., Whang-Peng J., Kao-Shan C.S., Tam M.F., Lai H.-C.J., Tu C.-P.D.
J. Biol. Chem. 263:12797-12800(1988) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE OF 1-9.
[12]"Characterization of two novel subunits of the alpha-class glutathione S-transferases of human liver."
Ahmad H., Singhal S.S., Saxena M., Awasthi Y.C.
Biochim. Biophys. Acta 1161:333-336(1993) [PubMed] [Europe PMC] [Abstract]
Cited for: PROTEIN SEQUENCE OF 2-170; 188-195 AND 209-222.
[13]"Evidence that glutathione S-transferases B1B1 and B2B2 are the products of separate genes and that their expression in human liver is subject to inter-individual variation. Molecular relationships between the B1 and B2 subunits and other alpha class glutathione S-transferases."
Hayes J.D., Kerr L.A., Cronshaw A.D.
Biochem. J. 264:437-445(1989) [PubMed] [Europe PMC] [Abstract]
Cited for: PROTEIN SEQUENCE OF 16-36; 63-155 AND 208-212.
[14]"The contribution of the C-terminal sequence to the catalytic activity of GST2, a human alpha-class glutathione transferase."
Board P.G., Mannervik B.
Biochem. J. 275:171-174(1991) [PubMed] [Europe PMC] [Abstract]
Cited for: PROTEIN SEQUENCE OF 200-222.
[15]"Structure determination and refinement of human alpha class glutathione transferase A1-1, and a comparison with the Mu and Pi class enzymes."
Sinning I., Kleywegt G.J., Cowan S.W., Reinemer P., Dirr H.W., Huber R., Gilliland G.L., Armstrong R.N., Ji X., Board P.G., Olin B., Mannervik B., Jones T.A.
J. Mol. Biol. 232:192-212(1993) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.6 ANGSTROMS) IN COMPLEX WITH S-BENZYL-GLUTATHIONE, SUBUNIT.
[16]"Structural analysis of human alpha-class glutathione transferase A1-1 in the apo-form and in complexes with ethacrynic acid and its glutathione conjugate."
Cameron A.D., Sinning I., L'Hermite G., Olin B., Board P.G., Mannervik B., Jones T.A.
Structure 3:717-727(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS) IN COMPLEXES WITH ETHACRYNIC ACID AND GLUTATHIONE, SUBUNIT.
[17]"1.3-A resolution structure of human glutathione S-transferase with S-hexyl glutathione bound reveals possible extended ligandin binding site."
Le Trong I., Stenkamp R.E., Ibarra C., Atkins W.M., Adman E.T.
Proteins 48:618-627(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (1.3 ANGSTROMS) IN COMPLEXES WITH S-HEXYL GLUTATHIONE, SUBUNIT.
[18]"Incorporation of a single His residue by rational design enables thiol-ester hydrolysis by human glutathione transferase A1-1."
Hederos S., Broo K.S., Jakobsson E., Kleywegt G.J., Mannervik B., Baltzer L.
Proc. Natl. Acad. Sci. U.S.A. 101:13163-13167(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.07 ANGSTROMS) IN COMPLEX WITH S-BENZYLGLUTATHIONE, MUTAGENESIS OF ALA-216.
[19]"Tertiary interactions stabilise the C-terminal region of human glutathione transferase A1-1: a crystallographic and calorimetric study."
Kuhnert D.C., Sayed Y., Mosebi S., Sayed M., Sewell T., Dirr H.W.
J. Mol. Biol. 349:825-838(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (1.95 ANGSTROMS) OF MUTANT ALA-219 IN COMPLEX WITH S-HEXYLGLUTATHIONE.
[20]"New crystal structures of human glutathione transferase A1-1 shed light on glutathione binding and the conformation of the C-terminal helix."
Grahn E., Novotny M., Jakobsson E., Gustafsson A., Grehn L., Olin B., Madsen D., Wahlberg M., Mannervik B., Kleywegt G.J.
Acta Crystallogr. D 62:197-207(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (1.75 ANGSTROMS) IN COMPLEX WITH GLUTATHIONE, SUBUNIT.
[21]"Structural analysis of a glutathione transferase A1-1 mutant tailored for high catalytic efficiency with toxic alkenals."
Balogh L.M., Le Trong I., Kripps K.A., Tars K., Stenkamp R.E., Mannervik B., Atkins W.M.
Biochemistry 48:7698-7704(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (1.98 ANGSTROMS) OF 1-210 IN COMPLEX WITH GLUTATHIONE.
[22]"The role of a topologically conserved isoleucine in glutathione transferase structure, stability and function."
Achilonu I., Gildenhuys S., Fisher L., Burke J., Fanucchi S., Sewell B.T., Fernandes M., Dirr H.W.
Acta Crystallogr. F 66:776-780(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (1.75 ANGSTROMS) OF MUTANTS ALA-71 AND VAL-71 IN COMPLEX WITH S-HEXYLGLUTATHIONE, FUNCTION, CATALYTIC ACTIVITY, MUTAGENESIS OF ILE-71.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
M15872 mRNA. Translation: AAA70226.1.
M21758 mRNA. Translation: AAA52615.1.
M25627 mRNA. Translation: AAA36174.1.
M14777 mRNA. Translation: AAA52618.1.
S76235 expand/collapse EMBL AC list , S76221, S76223, S76225, S76228, S76232 Genomic DNA. Translation: AAB20973.1.
S49975 mRNA. Translation: AAB24012.1.
AY532928 mRNA. Translation: AAT06769.1.
CR407656 mRNA. Translation: CAG28584.1.
AL590363 Genomic DNA. Translation: CAI13812.1.
CH471081 Genomic DNA. Translation: EAX04385.1.
BC053578 mRNA. Translation: AAH53578.1.
BC110891 mRNA. Translation: AAI10892.1.
PIRA56666. A25909.
S29657.
RefSeqNP_665683.1. NM_145740.3.
UniGeneHs.446309.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1GSDX-ray2.50A/B/C/D2-222[»]
1GSEX-ray2.00A/B2-222[»]
1GSFX-ray2.70A/B/C/D2-222[»]
1GUHX-ray2.60A/B/C/D2-222[»]
1K3LX-ray1.50A/B2-221[»]
1K3OX-ray1.80A/B2-221[»]
1K3YX-ray1.30A/B2-221[»]
1LBKX-ray1.86A/B208-213[»]
1PKWX-ray2.00A/B1-222[»]
1PKZX-ray2.10A/B1-222[»]
1PL1X-ray1.75A/B1-222[»]
1PL2X-ray1.80A/B1-222[»]
1USBX-ray2.07A/B2-222[»]
1XWGX-ray1.85A/B2-222[»]
1YDKX-ray1.95A/B2-221[»]
2R3XX-ray1.80A/B1-222[»]
2R6KX-ray2.51A/B1-222[»]
3I69X-ray2.38A/B/C/D/E/F/G/H1-210[»]
3I6AX-ray1.98A/B/C/D/E/F/G/H1-210[»]
3IK9X-ray2.20A/B/C/D/E/F/G/H1-210[»]
3KTLX-ray1.75A/B2-222[»]
3L0HX-ray2.13A/B1-222[»]
3Q74X-ray1.79A/B2-222[»]
3U6VX-ray2.20A/B1-222[»]
3ZFBX-ray1.86A/B1-222[»]
3ZFLX-ray1.88A/B1-222[»]
4HJ2X-ray2.10A/B4-220[»]
ProteinModelPortalP08263.
SMRP08263. Positions 2-222.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid109193. 8 interactions.
IntActP08263. 6 interactions.
MINTMINT-5000131.
STRING9606.ENSP00000335620.

Chemistry

BindingDBP08263.
ChEMBLCHEMBL3409.
DrugBankDB00276. Amsacrine.
DB01008. Busulfan.
DB00143. Glutathione.

PTM databases

PhosphoSiteP08263.

Polymorphism databases

DMDM121730.

2D gel databases

REPRODUCTION-2DPAGEIPI00657682.

Proteomic databases

PaxDbP08263.
PRIDEP08263.

Protocols and materials databases

DNASU2938.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000334575; ENSP00000335620; ENSG00000243955.
GeneID2938.
KEGGhsa:2938.
UCSCuc003paz.3. human.

Organism-specific databases

CTD2938.
GeneCardsGC06M052656.
HGNCHGNC:4626. GSTA1.
HPAHPA004342.
HPA053817.
MIM138359. gene.
neXtProtNX_P08263.
PharmGKBPA29016.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG266414.
HOGENOMHOG000115734.
HOVERGENHBG053749.
InParanoidP08263.
KOK00799.
OMADTNILAN.
OrthoDBEOG79CZ0K.
PhylomeDBP08263.
TreeFamTF105321.

Enzyme and pathway databases

BioCycMetaCyc:G66-32542-MONOMER.
ReactomeREACT_111217. Metabolism.
SABIO-RKP08263.

Gene expression databases

BgeeP08263.
CleanExHS_GSTA1.
GenevestigatorP08263.

Family and domain databases

Gene3D1.20.1050.10. 1 hit.
3.40.30.10. 1 hit.
InterProIPR010987. Glutathione-S-Trfase_C-like.
IPR004045. Glutathione_S-Trfase_N.
IPR003080. GST_alpha.
IPR004046. GST_C.
IPR012336. Thioredoxin-like_fold.
[Graphical view]
PANTHERPTHR11571:SF4. PTHR11571:SF4. 1 hit.
PfamPF00043. GST_C. 1 hit.
PF02798. GST_N. 1 hit.
[Graphical view]
PRINTSPR01266. GSTRNSFRASEA.
SUPFAMSSF47616. SSF47616. 1 hit.
SSF52833. SSF52833. 1 hit.
PROSITEPS50405. GST_CTER. 1 hit.
PS50404. GST_NTER. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

EvolutionaryTraceP08263.
GeneWikiGlutathione_S-transferase_A1.
GenomeRNAi2938.
NextBio11643.
PROP08263.
SOURCESearch...

Entry information

Entry nameGSTA1_HUMAN
AccessionPrimary (citable) accession number: P08263
Secondary accession number(s): Q14750, Q5GHF8, Q5SZC1
Entry history
Integrated into UniProtKB/Swiss-Prot: August 1, 1988
Last sequence update: January 23, 2007
Last modified: April 16, 2014
This is version 162 of the entry and version 3 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 6

Human chromosome 6: entries, gene names and cross-references to MIM