GSTA1 glutathione S-transferase alpha 1 [Homo sapiens (human)] - Gene

Summary

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Official Symbol: GSTA1provided by HGNC
Official Full Name: glutathione S-transferase alpha 1provided by HGNC
Primary source: HGNC:4626
Locus tag: RP11-392A23.1
See related: HPRD:00708; MIM:138359
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: GST2; GTH1; GSTA1-1
Summary: Cytosolic and membrane-bound forms of glutathione S-transferase are encoded by two distinct supergene families. These enzymes function in the detoxification of electrophilic compounds, including carcinogens, therapeutic drugs, environmental toxins and products of oxidative stress, by conjugation with glutathione. The genes encoding these enzymes are known to be highly polymorphic. These genetic variations can change an individual's susceptibility to carcinogens and toxins as well as affect the toxicity and efficacy of some drugs. At present, eight distinct classes of the soluble cytoplasmic mammalian glutathione S-transferases have been identified: alpha, kappa, mu, omega, pi, sigma, theta and zeta. This gene encodes a glutathione S-tranferase belonging to the alpha class. The alpha class genes, located in a cluster mapped to chromosome 6, are the most abundantly expressed glutathione S-transferases in liver. In addition to metabolizing bilirubin and certain anti-cancer drugs in the liver, the alpha class of these enzymes exhibit glutathione peroxidase activity thereby protecting the cells from reactive oxygen species and the products of peroxidation. [provided by RefSeq, Jul 2008]

Genomic context

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Location :: 6p12.1

Sequence :: Chromosome: 6; NC_000006.11 (52656178..52668664, complement)

See GSTA1 in Epigenomics, MapViewer

Chromosome 6 - NC_000006.11 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Genomic Sequence

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Go to reference sequence details

Bibliography

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GeneRIFs: Gene References Into Functions What's a GeneRIF?

Variability in GST genes (GSTA1, GSTT1, GSTP1, GSTA1) is not a major determinant of colorectal cancer susceptibility in the Central European population.
Title: Common polymorphisms in GSTM1, GSTT1, GSTP1, GSTA1 and susceptibility to colorectal cancer in the Central European population.
Results confirmed that patients with schizophrenia who were carriers of the GSTA1 *B risk allele had an increased MD in bilateral thalami and increased severity of auditory and global hallucinations in comparison with non-B carriers.
Title: Glutathione S-transferase alpha 1 risk polymorphism and increased bilateral thalamus mean diffusivity in schizophrenia.
Polymorphisms in genes encoding interleukin-10 and drug metabolizing enzymes GSTP1, GSTT1, GSTA1 and UGT1A1 influence risk and outcome in Hodgkin lymphoma.
Title: Polymorphisms in genes encoding interleukin-10 and drug metabolizing enzymes GSTP1, GSTT1, GSTA1 and UGT1A1 influence risk and outcome in Hodgkin lymphoma.
The data suggest that menadione-induced JNK activation involves the production of reactive oxygen species, likely superoxide anion, and intracellular GSH levels play an important role in preventing GSTA1-JNK complex dissociation.
Title: The effect of menadione on glutathione S-transferase A1 (GSTA1): c-Jun N-terminal kinase (JNK) complex dissociation in human colonic adenocarcinoma Caco-2 cells.
Tyr-9-induced localisation of a C-terminal helix (alpha9)of glutathione transferase A1-1 was ligand dependent, suggesting that the phenolic hydroxyl group of the active site tyrosine influences alpha9 dynamics by mediating the orientation of the bound ligand.
Title: Energetics of ligand binding to human glutathione transferase A1-1: Tyr-9 associated localisation of the C-terminal helix is ligand-dependent.
A significant association is found between the GSTA1 gene and an increased risk of recurrent miscarriage.
Title: Glutathione S-transferase genes and the risk of recurrent miscarriage in Italian women.
GSTA1 and the GSTO2 are asthma susceptible genes involved in increasing the risk of asthma development in the Italian population
Title: Functional polymorphisms of GSTA1 and GSTO2 genes associated with asthma in Italian children.
After adjustment of confounding factors, GSTP1 Ile105Val, GSTA1 C-69T, and TGFbeta1 T869C polymorphisms were found to be significantly associated with the risk of Grade 2-3 radiation-induced fibrosis.
Title: Common variants of GSTP1, GSTA1, and TGFβ1 are associated with the risk of radiation-induced fibrosis in breast cancer patients.
By direct resequencing of the 5'-flanking region, all the exons, and their flanking introns for 107 patients, 29 and 27 variants were identified in GSTA1 and GSTA2, respectively.
Title: Genetic variation and haplotype structures of the glutathione S-transferase genes GSTA1 and GSTA2 in Japanese colorectal cancer patients.
The barrierless rearrangement of the GSTA1-1 active site within a local smooth energy landscape suggests a thermodynamic basis for catalytic promiscuity
Title: Ensemble perspective for catalytic promiscuity: calorimetric analysis of the active site conformational landscape of a detoxification enzyme.

Submit: New GeneRIF Correction See all (80)

Phenotypes

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Review eQTL and phenotype association data in this region using PheGenI

Interactions

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Products	Interactant	Other Gene	Source	Pubs	Description
P08263	P08263	GSTA1	HPRD	PubMed
P08263	P09210	GSTA2	HPRD	PubMed
BioGRID:109193	BioGRID:106848	APP	BioGRID	PubMed	Reconstituted Complex
BioGRID:109193	BioGRID:109193	GSTA1	BioGRID	PubMed	Co-purification
BioGRID:109193	BioGRID:118105	LSM3	BioGRID	PubMed	Two-hybrid
BioGRID:109193	BioGRID:111508	PPP2CB	BioGRID	PubMed	Two-hybrid
BioGRID:109193	BioGRID:123995	RPAIN	BioGRID	PubMed	Two-hybrid
BioGRID:109193	BioGRID:112375	ST3GAL1	BioGRID	PubMed	Two-hybrid
BioGRID:109193	BioGRID:113363	YWHAE	BioGRID	PubMed	Two-hybrid

Pathways from BioSystems

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4-hydroxy-2-nonenal detoxification, organism-specific biosystem (from BIOCYC)
4-hydroxy-2-nonenal detoxification, organism-specific biosystem
4-hydroxy-2-nonenal detoxification
4-hydroxy-2-nonenal detoxification, conserved biosystem (from BIOCYC)
4-hydroxy-2-nonenal detoxification, conserved biosystemGeneral Background |FRAME: CPD-10806 4-Hydroxy-2-nonenal| is a highly reactive neurotoxic product of lipid peroxidation that is implicated in the pathogenesis and progression of Alzheimer's and Park...
AhR pathway, organism-specific biosystem (from WikiPathways)
AhR pathway, organism-specific biosystem
AhR pathway
Biological oxidations, organism-specific biosystem (from REACTOME)
Biological oxidations, organism-specific biosystemAll organisms are constantly exposed to foreign chemicals every day. These can be man-made (drugs, industrial chemicals) or natural (alkaloids, toxins from plants and animals). Uptake is usually via ...
Chemical carcinogenesis, organism-specific biosystem (from KEGG)
Chemical carcinogenesis, organism-specific biosystemIt has been estimated that exposure to environmental chemical carcinogens may contribute significantly to the causation of a sizable fraction, perhaps a majority, of human cancers. Human carcinogens ...
Chemical carcinogenesis, conserved biosystem (from KEGG)
Chemical carcinogenesis, conserved biosystemIt has been estimated that exposure to environmental chemical carcinogens may contribute significantly to the causation of a sizable fraction, perhaps a majority, of human cancers. Human carcinogens ...
Drug metabolism - cytochrome P450, organism-specific biosystem (from KEGG)
Drug metabolism - cytochrome P450, organism-specific biosystem
Drug metabolism - cytochrome P450
Drug metabolism - cytochrome P450, conserved biosystem (from KEGG)
Drug metabolism - cytochrome P450, conserved biosystem
Drug metabolism - cytochrome P450
Glutathione conjugation, organism-specific biosystem (from REACTOME)
Glutathione conjugation, organism-specific biosystemGlutathione S-Transferases (GSTs; EC 2.5.1.18) are another major set of phase II conjugation enzymes. They can be found in the cytosol as well as being microsomal membrane-bound. Cytosolic GSTs are e...
Glutathione metabolism, organism-specific biosystem (from KEGG)
Glutathione metabolism, organism-specific biosystem
Glutathione metabolism
Glutathione metabolism, organism-specific biosystem (from WikiPathways)
Glutathione metabolism, organism-specific biosystem
Glutathione metabolism
Glutathione metabolism, conserved biosystem (from KEGG)
Glutathione metabolism, conserved biosystem
Glutathione metabolism
Metabolism, organism-specific biosystem (from REACTOME)
Metabolism, organism-specific biosystemMetabolic processes in human cells generate energy through the oxidation of molecules consumed in the diet and mediate the synthesis of diverse essential molecules not taken in the diet as well as th...
Metabolism of xenobiotics by cytochrome P450, organism-specific biosystem (from KEGG)
Metabolism of xenobiotics by cytochrome P450, organism-specific biosystem
Metabolism of xenobiotics by cytochrome P450
Metabolism of xenobiotics by cytochrome P450, conserved biosystem (from KEGG)
Metabolism of xenobiotics by cytochrome P450, conserved biosystem
Metabolism of xenobiotics by cytochrome P450
Phase II conjugation, organism-specific biosystem (from REACTOME)
Phase II conjugation, organism-specific biosystemPhase II of biotransformation is concerned with conjugation, that is using groups from cofactors to react with functional groups present or introduced from phase I on the compound. The enzymes involv...
glutathione-mediated detoxification I, organism-specific biosystem (from BIOCYC)
glutathione-mediated detoxification I, organism-specific biosystemPlease note: This is a general detoxification pathway, where the first step can be catalyzed by many different enzymes, collectively known as glutathione transferases, or GSTs. In the first reaction,...
glutathione-mediated detoxification I, conserved biosystem (from BIOCYC)
glutathione-mediated detoxification I, conserved biosystemPlease note: This is a general detoxification pathway, where the first step can be catalyzed by many different enzymes, collectively known as glutathione transferases, or GSTs. In the first reaction,...

General gene information

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Markers

G66731 (e-PCR)
- UniSTS:166944

G66732 (e-PCR)
- UniSTS:166945

G66733 (e-PCR)
- UniSTS:166946

RH15792 (e-PCR)
- UniSTS:48990

GSTA2_2506 (e-PCR)
- UniSTS:280745

Homology

Homologs of the GSTA1 gene: The GSTA1 gene is conserved in chimpanzee, Rhesus monkey, cow, and rat.
Map Viewer (Rat)
OrthoDB: The Hierarchical Catalog of Eukaryotic Orthologs

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
glutathione transferase activity	IDA Inferred from Direct Assay more info	PubMed
glutathione transferase activity	NAS Non-traceable Author Statement more info	PubMed

Process	Evidence Code	Pubs
glutathione metabolic process	IDA Inferred from Direct Assay more info	PubMed
metabolic process	IC Inferred by Curator more info	PubMed
small molecule metabolic process	TAS Traceable Author Statement more info
xenobiotic metabolic process	TAS Traceable Author Statement more info

Component	Evidence Code	Pubs
cytoplasm	NAS Non-traceable Author Statement more info
cytosol	TAS Traceable Author Statement more info

General protein information

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Preferred Names: glutathione S-transferase A1

Names: glutathione S-transferase A1; GST-epsilon; GST HA subunit 1; GST, class alpha, 1; GST class-alpha member 1; glutathione S-transferase 2; glutathione S-aryltransferase A1; glutathione S-alkyltransferase A1; S-(hydroxyalkyl)glutathione lyase A1; glutathione S-transferase Ha subunit 1

NP_665683.1

EC 2.5.1.18

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

mRNA and Protein(s)

NM_145740.3 → NP_665683.1 glutathione S-transferase A1

Status: REVIEWED

Source sequence(s)

BC053578, BM973137, DC339498

Consensus CDS

CCDS4945.1

UniProtKB/Swiss-Prot

P08263

Conserved Domains (3) summary

cd03077
Location:4 – 82
Blast Score: 387

GST_N_Alpha; GST_N family, Class Alpha subfamily; GSTs are cytosolic dimeric proteins involved in cellular detoxification by catalyzing the conjugation of glutathione (GSH) with a wide range of endogenous and xenobiotic alkylating agents, including carcinogens, ...

PTZ00057
Location:1 – 198
Blast Score: 216

PTZ00057; glutathione s-transferase; Provisional

cd03208
Location:86 – 220
Blast Score: 564

GST_C_Alpha; C-terminal, alpha helical domain of Class Alpha Glutathione S-transferases

RefSeqs of Annotated Genomes: Homo sapiens Annotation Release 104

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh37.p10 Primary Assembly

Genomic

NC_000006.11 Reference GRCh37.p10 Primary Assembly

Range

52656178..52668664, complement

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GenBank, FASTA, Sequence Viewer (Graphics)

Alternate HuRef

Genomic

AC_000138.1 Alternate HuRef

Range

52486923..52499385, complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

Alternate CHM1_1.0

Genomic

NC_018917.1 Alternate CHM1_1.0

Range

52569149..52581533, complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

Nucleotide		Protein
Heading	Accession and Version	Protein
genomic	ABBA01050547.1 (148267..160729)	None
genomic	AL590363.6 (5175..17661)	None
genomic	AMYH01016354.1 (135328..147712)	None
genomic	CH471081.1	EAX04385.1
genomic	S76235.1	AAB20973.1
mRNA	AK293371.1	BAH11495.1
mRNA	AK310324.1	None
mRNA	AY532928.1	AAT06769.1
mRNA	BC053578.1	AAH53578.1
mRNA	BC110891.1	AAI10892.1
mRNA	BG430521.1	None
mRNA	BI762344.1	None
mRNA	BM973137.1	None
mRNA	CA841071.1	None
mRNA	CR407656.1	CAG28584.1
mRNA	DC339498.1	None
mRNA	M14777.1	AAA52618.1
mRNA	M15872.1	AAA70226.1
mRNA	M21758.1	AAA52615.1
mRNA	M25627.1	AAA36174.1
mRNA	S49975.1	AAB24012.1
other-genetic	HQ448093.1	ADQ32574.1