O15217 (GSTA4_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Glutathione S-transferase A4
EC=2.5.1.18

Alternative name(s):
GST class-alpha member 4
Glutathione S-transferase A4-4

Gene names

Name:

GSTA4

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	222 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Conjugation of reduced glutathione to a wide number of exogenous and endogenous hydrophobic electrophiles. This isozyme has a high catalytic efficiency with 4-hydroxyalkenals such as 4-hydroxynonenal (4-HNE). Ref.11 Ref.12
Catalytic activity	RX + glutathione = HX + R-S-glutathione. Ref.11 Ref.12
Subunit structure	Homodimer. Ref.11
Subcellular location	Cytoplasm.
Tissue specificity	Expressed at a high level in brain, placenta, and skeletal muscle and much lower in lung and liver.
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 Reference proteome
Gene Ontology (GO)
Biological process	glutathione metabolic process Inferred from direct assay Ref.11. Source: UniProtKB xenobiotic metabolic process Inferred from direct assay Ref.11. Source: UniProtKB
Cellular component	cytosol Traceable author statement. Source: Reactome
Molecular function	glutathione transferase activity Inferred from direct assay Ref.11. Source: UniProtKB protein homodimerization activity Inferred from physical interaction Ref.11. Source: UniProtKB
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 222

222

Glutathione S-transferase A4

PRO_0000185786

Regions

Domain

3 – 83

81

GST N-terminal

Domain

85 – 208

124

GST C-terminal

Region

54 – 55

2

Glutathione binding

Region

67 – 68

2

Glutathione binding

Sites

Binding site

9

1

Glutathione

Binding site

212

1

Substrate

Natural variations

Natural variant

100

1

L → P. Ref.6
Corresponds to variant rs45551133 [ dbSNP | Ensembl ].

VAR_022210

Natural variant

163

1

T → A. Ref.6
Corresponds to variant rs4147617 [ dbSNP | Ensembl ].

VAR_022211

Experimental info

Mutagenesis

9

1

Y → F: Reduces catalytic activity 70-fold. Ref.12

Mutagenesis

212

1

Y → A, F or S: Strongly reduced activity towards 4-hydroxynon-2-enal and 1-chloro-2,4-dinitrobenzene. Ref.11

Secondary structure

1

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222

Helix Strand Turn

Details...

Beta strand

6 – 12

7

Turn

14 – 16

3

Helix

17 – 25

9

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 – 131

18

Helix

133 – 143

11

Beta strand

146 – 149

4

Helix

155 – 170

16

Turn

172 – 177

6

Helix

179 – 188

10

Helix

192 – 198

7

Helix

210 – 219

10

Sequences

	Sequence		Length	Mass (Da)
	O15217 [UniParc]. Last modified January 1, 1998. Version 1. Checksum: 1BD98B41E413BB4E	FASTA	222	25,704
	10 20 30 40 50 60 MAARPKLHYP NGRGRMESVR WVLAAAGVEF DEEFLETKEQ LYKLQDGNHL LFQQVPMVEI 70 80 90 100 110 120 DGMKLVQTRS ILHYIADKHN LFGKNLKERT LIDMYVEGTL DLLELLIMHP FLKPDDQQKE 130 140 150 160 170 180 VVNMAQKAII RYFPVFEKIL RGHGQSFLVG NQLSLADVIL LQTILALEEK IPNILSAFPF 190 200 210 220 LQEYTVKLSN IPTIKRFLEP GSKKKPPPDE IYVRTVYNIF RP

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Human glutathione transferase A4-4: an alpha class enzyme with high catalytic efficiency in the conjugation of 4-hydroxynonenal and other genotoxic products of lipid peroxidation." Hubatsch I., Ridderstrom M., Mannervik B. Biochem. J. 330:175-179(1998) [PubMed: 9461507] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Brain.
[2]	"Identification of cDNAs encoding two human alpha class glutathione transferases (GSTA3 and GSTA4) and the heterologous expression of GSTA4-4." Board P.G. Biochem. J. 330:827-831(1998) [PubMed: 9480897] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[3]	"Identification of a novel human glutathione S-transferase using bioinformatics." Liu S., Stoesz S.P., Pickett C.B. Arch. Biochem. Biophys. 352:306-313(1998) [PubMed: 9587421] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[4]	"The 4-HNE metabolizing GST isozyme hGSTA4-4 is expressed in human heart, pancreas, and skeletal muscle." Piper J.T., Awasthi Y.C. Submitted (FEB-1999) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Heart, Pancreas and Skeletal muscle.
[5]	"Genomic organization, 5'-flanking region and chromosomal localization of the human glutathione transferase A4 gene." Desmots F., Rauch C., Henry C., Guillouzo A., Morel F. Biochem. J. 336:437-442(1998) [PubMed: 9820822] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[6]	NIEHS SNPs program Submitted (JAN-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS PRO-100 AND ALA-163.
[7]	"Complete sequencing and characterization of 21,243 full-length human cDNAs." Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S. Nat. Genet. 36:40-45(2004) [PubMed: 14702039] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Cerebellum.
[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: 14574404] [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: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Uterus.
[11]	"Human glutathione transferase A4-4 crystal structures and mutagenesis reveal the basis of high catalytic efficiency with toxic lipid peroxidation products." Bruns C.M., Hubatsch I., Ridderstroem M., Mannervik B., Tainer J.A. J. Mol. Biol. 288:427-439(1999) [PubMed: 10329152] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.7 ANGSTROMS) IN COMPLEX WITH 2-IODOBENZYL GLUTATHIONE, CATALYTIC ACTIVITY, FUNCTION, MUTAGENESIS OF TYR-212, SUBUNIT.
[12]	"Substrate specificity combined with stereopromiscuity in glutathione transferase A4-4-dependent metabolism of 4-hydroxynonenal." Balogh L.M., Le Trong I., Kripps K.A., Shireman L.M., Stenkamp R.E., Zhang W., Mannervik B., Atkins W.M. Biochemistry 49:1541-1548(2010) [PubMed: 20085333] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.97 ANGSTROMS) IN COMPLEX WITH SUBSTRATE ANALOG, CATALYTIC ACTIVITY, FUNCTION, MUTAGENESIS OF TYR-9.
+	Additional computationally mapped references.

Web resources

NIEHS-SNPs

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

Y13047 mRNA. Translation: CAA73482.1.
AF020918 mRNA. Translation: AAD04711.1.
AF025887 mRNA. Translation: AAC39695.1.
AF125271 mRNA. Translation: AAD27704.1.
AF125272 mRNA. Translation: AAD27705.1.
AF125273 mRNA. Translation: AAD27706.1.
AF050059 , AF050054, AF050055, AF050056, AF050057, AF050058 Genomic DNA. Translation: AAC72706.1.
AY878121 Genomic DNA. Translation: AAW56075.1.
AK315369 mRNA. Translation: BAG37762.1.
AL121969, AL162581 Genomic DNA. Translation: CAI42451.1.
AL162581, AL121969 Genomic DNA. Translation: CAI19517.1.
CH471081 Genomic DNA. Translation: EAX04394.1.
BC015523 mRNA. Translation: AAH15523.1.

IPI

IPI00005659.

RefSeq

NP_001503.1. NM_001512.3.

UniGene

Hs.485557.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1GUL	X-ray	2.70	A/B/C/D/E/F/G/H	1-222	[»]
1GUM	X-ray	3.00	A/B/C/D/E/F/G/H	1-222	[»]
3IK7	X-ray	1.97	A/B/C/D	1-222	[»]

ProteinModelPortal

O15217.

SMR

O15217. Positions 2-222.

ModBase

Search...

Protein-protein interaction databases

IntAct

O15217. 1 interaction.

MINT

MINT-1466182.

STRING

O15217.

PTM databases

PhosphoSite

O15217.

Proteomic databases

PRIDE

O15217.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000370959; ENSP00000359998; ENSG00000170899.
ENST00000370963; ENSP00000360002; ENSG00000170899.

GeneID

2941.

KEGG

hsa:2941.

UCSC

uc003pbc.1. human.

Organism-specific databases

CTD

2941.

GeneCards

GC06M052889.

H-InvDB

HIX0005958.

HGNC

HGNC:4629. GSTA4.

MIM

605450. gene.

neXtProt

NX_O15217.

PharmGKB

PA29019.

GenAtlas

Search...

Phylogenomic databases

eggNOG

prNOG06848.

HOGENOM

HBG443985.

HOVERGEN

HBG053749.

InParanoid

O15217.

OMA

TVYNIFM.

OrthoDB

EOG4N5VXR.

PhylomeDB

O15217.

Enzyme and pathway databases

Reactome

REACT_111217. Metabolism.

Gene expression databases

ArrayExpress

O15217.

Bgee

O15217.

CleanEx

HS_GSTA4.

Genevestigator

O15217.

GermOnline

ENSG00000170899. Homo sapiens.

Family and domain databases

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]

Gene3D

G3DSA:1.20.1050.10. GST_C_like. 1 hit.
G3DSA:3.40.30.10. Thioredoxin_fold. 1 hit.

KO

K00799.

PANTHER

PTHR11571:SF4. GST_alpha. 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

DrugBank

DB00143. Glutathione.

NextBio

11655.

SOURCE

Search...

Entry information

Entry name

GSTA4_HUMAN

Accession

Primary (citable) accession number: O15217
Secondary accession number(s): B2RD15 , Q5T7Q8, Q9BX18, Q9H414

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 15, 1999
Last sequence update:	January 1, 1998
Last modified:	January 25, 2012
This is version 113 of the entry and version 1 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.