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O15217 (GSTA4_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 134. 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·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended 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
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length222 AA.
Sequence statusComplete.
Protein existenceEvidence 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.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 222222Glutathione S-transferase A4
PRO_0000185786

Regions

Domain3 – 8381GST N-terminal
Domain85 – 208124GST C-terminal
Region54 – 552Glutathione binding
Region67 – 682Glutathione binding

Sites

Binding site91Glutathione
Binding site2121Substrate

Amino acid modifications

Modified residue11N-acetylmethionine By similarity

Natural variations

Natural variant1001L → P. Ref.6
Corresponds to variant rs45551133 [ dbSNP | Ensembl ].
VAR_022210
Natural variant1631T → A. Ref.6
Corresponds to variant rs4147617 [ dbSNP | Ensembl ].
VAR_022211

Experimental info

Mutagenesis91Y → F: Reduces catalytic activity 70-fold. Ref.12
Mutagenesis2121Y → A, F or S: Strongly reduced activity towards 4-hydroxynon-2-enal and 1-chloro-2,4-dinitrobenzene. Ref.11

Secondary structure

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

Details...

Sequences

Sequence LengthMass (Da)Tools
O15217 [UniParc].

Last modified January 1, 1998. Version 1.
Checksum: 1BD98B41E413BB4E

FASTA22225,704
        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 

« Hide

References

« Hide '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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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. expand/collapse author list , 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] [Europe PMC] [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. 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: 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] [Europe PMC] [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] [Europe PMC] [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

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 expand/collapse EMBL AC list , 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.
RefSeqNP_001503.1. NM_001512.3.
XP_005249092.1. XM_005249035.1.
UniGeneHs.485557.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1GULX-ray2.70A/B/C/D/E/F/G/H1-222[»]
1GUMX-ray3.00A/B/C/D/E/F/G/H1-222[»]
3IK7X-ray1.97A/B/C/D1-222[»]
ProteinModelPortalO15217.
SMRO15217. Positions 2-222.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid109196. 3 interactions.
MINTMINT-1466182.
STRING9606.ENSP00000359998.

Chemistry

ChEMBLCHEMBL4933.
DrugBankDB00143. Glutathione.

PTM databases

PhosphoSiteO15217.

Proteomic databases

PaxDbO15217.
PRIDEO15217.

Protocols and materials databases

DNASU2941.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000370959; ENSP00000359998; ENSG00000170899.
ENST00000370963; ENSP00000360002; ENSG00000170899.
GeneID2941.
KEGGhsa:2941.
UCSCuc003pbd.3. human.

Organism-specific databases

CTD2941.
GeneCardsGC06M052842.
HGNCHGNC:4629. GSTA4.
HPAHPA048934.
MIM605450. gene.
neXtProtNX_O15217.
PharmGKBPA29019.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG266414.
HOGENOMHOG000115734.
HOVERGENHBG053749.
InParanoidO15217.
KOK00799.
OMAIIMHPFL.
OrthoDBEOG79CZ0K.
PhylomeDBO15217.
TreeFamTF105321.

Enzyme and pathway databases

ReactomeREACT_111217. Metabolism.

Gene expression databases

ArrayExpressO15217.
BgeeO15217.
CleanExHS_GSTA4.
GenevestigatorO15217.

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

EvolutionaryTraceO15217.
GeneWikiGSTA4.
GenomeRNAi2941.
NextBio11655.
PROO15217.
SOURCESearch...

Entry information

Entry nameGSTA4_HUMAN
AccessionPrimary (citable) accession number: O15217
Secondary accession number(s): B2RD15 expand/collapse secondary AC list , Q5T7Q8, Q9BX18, Q9H414
Entry history
Integrated into UniProtKB/Swiss-Prot: July 15, 1999
Last sequence update: January 1, 1998
Last modified: April 16, 2014
This is version 134 of the entry and version 1 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