P08263 (GSTA1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended 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

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	222 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence 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.

Ontologies

Keywords
Cellular component	Cytoplasm
Coding sequence diversity	Polymorphism
Molecular function	Transferase
Technical term	3D-structure Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	glutathione metabolic process Inferred from direct assay Ref.22. Source: UniProtKB xenobiotic metabolic process Traceable author statement. Source: Reactome
Cellular_component	cytosol Traceable author statement. Source: Reactome
Molecular_function	glutathione transferase activity Inferred from direct assay Ref.22. Source: UniProtKB
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Initiator methionine

1

1

Removed Ref.12

Chain

2 – 222

221

Glutathione S-transferase A1

PRO_0000185783

Regions

Domain

3 – 83

81

GST N-terminal

Domain

85 – 207

123

GST C-terminal

Region

54 – 55

2

Glutathione binding

Region

67 – 68

2

Glutathione binding

Sites

Binding site

9

1

Glutathione

Binding site

45

1

Glutathione

Natural variations

Natural variant

19

1

T → I.
Corresponds to variant rs1051578 [ dbSNP | Ensembl ].

VAR_033978

Natural variant

113

1

P → Q.
Corresponds to variant rs1051745 [ dbSNP | Ensembl ].

VAR_049482

Natural variant

117

1

K → Q.
Corresponds to variant rs1051757 [ dbSNP | Ensembl ].

VAR_049483

Experimental info

Mutagenesis

71

1

I → A or V: No significant effect on enzyme activity. Reduces protein stability. Ref.22

Mutagenesis

216

1

A → H: Confers ability to hydrolyze S-glutathionyl benzoate to glutathione and benzoic acid. Ref.18

Sequence conflict

18

1

S → C in AAA36174. Ref.3

Sequence conflict

51

1

M → T in AAT06769. Ref.7

Sequence conflict

56 – 58

3

PMV → AML in AAA36174. Ref.3

Sequence conflict

212

1

S → L AA sequence Ref.13

Sequence conflict

216

1

A → S AA sequence Ref.12

Secondary structure

1

.

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222

Helix Strand Turn

Details...

Beta strand

6 – 13

8

Turn

14 – 16

3

Helix

17 – 26

10

Beta strand

31 – 35

5

Helix

38 – 46

9

Beta strand

57 – 60

4

Beta strand

63 – 67

5

Helix

68 – 78

11

Helix

86 – 108

23

Helix

109 – 111

3

Helix

114 – 130

17

Helix

132 – 143

12

Beta strand

146 – 149

4

Helix

155 – 170

16

Turn

172 – 177

6

Helix

179 – 190

12

Helix

192 – 198

7

Helix

210 – 220

11

Sequences

	Sequence		Length	Mass (Da)
	P08263 [UniParc]. Last modified January 23, 2007. Version 3. Checksum: C8B6786DCD761350	FASTA	222	25,631
	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

References

	« Hide 'large scale' referencesShow '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. , 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. , 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 , 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.

IPI

IPI00657682.

PIR

A56666. A25909.
S29657.

RefSeq

NP_665683.1. NM_145740.3.

UniGene

Hs.446309.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1GSD	X-ray	2.50	A/B/C/D	2-222	[»]
1GSE	X-ray	2.00	A/B	2-222	[»]
1GSF	X-ray	2.70	A/B/C/D	2-222	[»]
1GUH	X-ray	2.60	A/B/C/D	2-222	[»]
1K3L	X-ray	1.50	A/B	2-221	[»]
1K3O	X-ray	1.80	A/B	2-221	[»]
1K3Y	X-ray	1.30	A/B	2-221	[»]
1LBK	X-ray	1.86	A/B	208-213	[»]
1PKW	X-ray	2.00	A/B	1-222	[»]
1PKZ	X-ray	2.10	A/B	1-222	[»]
1PL1	X-ray	1.75	A/B	1-222	[»]
1PL2	X-ray	1.80	A/B	1-222	[»]
1USB	X-ray	2.07	A/B	2-222	[»]
1XWG	X-ray	1.85	A/B	2-222	[»]
1YDK	X-ray	1.95	A/B	2-221	[»]
2R3X	X-ray	1.80	A/B	1-222	[»]
2R6K	X-ray	2.51	A/B	1-222	[»]
3I69	X-ray	2.38	A/B/C/D/E/F/G/H	1-210	[»]
3I6A	X-ray	1.98	A/B/C/D/E/F/G/H	1-210	[»]
3IK9	X-ray	2.20	A/B/C/D/E/F/G/H	1-210	[»]
3KTL	X-ray	1.75	A/B	2-222	[»]
3L0H	X-ray	2.13	A/B	1-222	[»]
3Q74	X-ray	1.79	A/B	2-222	[»]
3U6V	X-ray	2.20	A/B	1-222	[»]
3ZFB	X-ray	1.86	A/B	1-222	[»]
3ZFL	X-ray	1.88	A/B	1-222	[»]

ProteinModelPortal

P08263.

ModBase

Search...

Protein-protein interaction databases

IntAct

P08263. 6 interactions.

STRING

9606.ENSP00000335620.

PTM databases

PhosphoSite

P08263.

Polymorphism databases

DMDM

121730.

2D gel databases

REPRODUCTION-2DPAGE

IPI00657682.

Proteomic databases

PaxDb

P08263.

PRIDE

P08263.

Protocols and materials databases

DNASU

2938.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000334575; ENSP00000335620; ENSG00000243955.

GeneID

2938.

KEGG

hsa:2938.

UCSC

uc003paz.3. human.

Organism-specific databases

CTD

2938.

GeneCards

GC06M052656.

HGNC

HGNC:4626. GSTA1.

HPA

HPA004342.

MIM

138359. gene.

neXtProt

NX_P08263.

PharmGKB

PA29016.

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG266414.

HOGENOM

HOG000115734.

HOVERGEN

HBG053749.

InParanoid

P08263.

KO

K00799.

OMA

DTNILAN.

OrthoDB

EOG479F80.

PhylomeDB

P08263.

Enzyme and pathway databases

BioCyc

MetaCyc:G66-32542-MONOMER.

Reactome

REACT_111217. Metabolism.

SABIO-RK

P08263.

Gene expression databases

Bgee

P08263.

CleanEx

HS_GSTA1.

Genevestigator

P08263.

GermOnline

ENSG00000187919. 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.
IPR003080. GST_alpha.
IPR004046. GST_C.
IPR012336. Thioredoxin-like_fold.
[Graphical view]

PANTHER

PTHR11571:SF4. PTHR11571:SF4. 1 hit.

Pfam

PF00043. GST_C. 1 hit.
PF02798. GST_N. 1 hit.
[Graphical view]

PRINTS

PR01266. GSTRNSFRASEA.

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

P08263.

ChEMBL

CHEMBL3409.

DrugBank

DB00276. Amsacrine.
DB01008. Busulfan.
DB00143. Glutathione.

EvolutionaryTrace

P08263.

GenomeRNAi

2938.

NextBio

11643.

SOURCE

Search...

Entry information

Entry name

GSTA1_HUMAN

Accession

Primary (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:	May 1, 2013
This is version 152 of the entry and version 3 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.