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GSTA4 glutathione S-transferase alpha 4 [ Homo sapiens (human) ]

Gene ID: 2941, updated on 3-Apr-2024

Summary

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Official Symbol
GSTA4provided by HGNC
Official Full Name
glutathione S-transferase alpha 4provided by HGNC
Primary source
HGNC:HGNC:4629
See related
Ensembl:ENSG00000170899 MIM:605450; AllianceGenome:HGNC:4629
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
GTA4; GSTA4-4
Summary
Cytosolic and membrane-bound forms of glutathione S-transferase are encoded by two distinct supergene families. These enzymes are involved in cellular defense against toxic, carcinogenic, and pharmacologically active electrophilic compounds. 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, which are located in a cluster on chromosome 6, are highly related and encode enzymes with glutathione peroxidase activity that function in the detoxification of lipid peroxidation products. Reactive electrophiles produced by oxidative metabolism have been linked to a number of degenerative diseases including Parkinson's disease, Alzheimer's disease, cataract formation, and atherosclerosis. [provided by RefSeq, Jul 2008]
Expression
Broad expression in adrenal (RPKM 149.4), skin (RPKM 38.6) and 16 other tissues See more
Orthologs
all
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Genomic context

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Location:
6p12.2
Exon count:
7
Annotation release Status Assembly Chr Location
RS_2023_10 current GRCh38.p14 (GCF_000001405.40) 6 NC_000006.12 (52977953..52995284, complement)
RS_2023_10 current T2T-CHM13v2.0 (GCF_009914755.1) 6 NC_060930.1 (52817518..52834853, complement)
105.20220307 previous assembly GRCh37.p13 (GCF_000001405.25) 6 NC_000006.11 (52842751..52860082, complement)

Chromosome 6 - NC_000006.12Genomic Context describing neighboring genes Neighboring gene uncharacterized LOC105375091 Neighboring gene H3K27ac hESC enhancer GRCh37_chr6:52774000-52774692 Neighboring gene H3K27ac hESC enhancer GRCh37_chr6:52774693-52775386 Neighboring gene glutathione S-transferase alpha 3 Neighboring gene OCT4-NANOG-H3K27ac hESC enhancer GRCh37_chr6:52787535-52788194 Neighboring gene Sharpr-MPRA regulatory region 1037 Neighboring gene glutathione S-transferase alpha 9, pseudogene Neighboring gene MPRA-validated peak5857 silencer Neighboring gene H3K27ac hESC enhancer GRCh37_chr6:52841001-52841876 Neighboring gene H3K27ac hESC enhancer GRCh37_chr6:52841877-52842750 Neighboring gene Neanderthal introgressed variant-containing enhancer experimental_92160 Neighboring gene ReSE screen-validated silencer GRCh37_chr6:52860003-52860234 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 24693 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 17287 Neighboring gene RNA component of 7SK nuclear ribonucleoprotein Neighboring gene ciliogenesis associated kinase 1 Neighboring gene uncharacterized LOC128092246

Genomic regions, transcripts, and products

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Go to nucleotide: Graphics FASTA GenBank

Expression

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  • Project title: HPA RNA-seq normal tissues
  • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
  • BioProject: PRJEB4337
  • Publication: PMID 24309898
  • Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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Related articles in PubMed

  1. Substrate specificity combined with stereopromiscuity in glutathione transferase A4-4-dependent metabolism of 4-hydroxynonenal. Balogh LM, et al. Biochemistry, 2010 Feb 23. PMID 20085333, Free PMC Article
  2. Association between polymorphisms in the GSTA4 gene and risk of lung cancer: a case-control study in a Southeastern Chinese population. Qian J, et al. Mol Carcinog, 2009 Mar. PMID 18767114
  3. Endothelial glutathione-S-transferase A4-4 protects against oxidative stress and modulates iNOS expression through NF-kappaB translocation. Yang Y, et al. Toxicol Appl Pharmacol, 2008 Jul 15. PMID 18485437, Free PMC Article
  4. Glutathione-S-transferase protects against oxidative injury of endothelial cell tight junctions. Xu Y, et al. Endothelium, 2007 Nov-Dec. PMID 18080870
  5. Transfection of HepG2 cells with hGSTA4 provides protection against 4-hydroxynonenal-mediated oxidative injury. Gallagher EP, et al. Toxicol In Vitro, 2007 Dec. PMID 17553661, Free PMC Article

See all (67) citations in PubMed

GeneRIFs: Gene References Into Functions

What's a GeneRIF?
  1. These findings demonstrate GSTA4 activation during 4-HNE-induced neoplastic transformation in colorectal carcinogenesis. GSTA4 is a potential surrogate biomarker for CRC screening and should provide novel approaches for chemoprevention.
    Title: Glutathione S-transferase alpha 4 induction by activator protein 1 in colorectal cancer.
  2. Decreased gene expression of GSTA4 is associated with drug resistance in cervical cancer.
    Title: Collateral sensitivity to cisplatin in KB-8-5-11 drug-resistant cancer cells.
  3. Data indicate that steroidogenic factor 1 (SF-1) and glutathione S-transferase A (GSTA) family genes (hGSTA1-hGSTA4) are involved in steroidogenesis.
    Title: Human glutathione S-transferase A (GSTA) family genes are regulated by steroidogenic factor 1 (SF-1) and are involved in steroidogenesis.
  4. drug resistance in three strains of tumor cells is associated with significant increase in hGSTP1 and hGSTA4 gene expression, whereas increased hGSTK1 gene expression was detected only in resistant erythroleukemia and mammary adenocarcinoma cells.
    Title: Expression of genes of glutathione transferase isoforms GSTP1-1, GSTA4-4, and GSTK1-1 in tumor cells during the formation of drug resistance to cisplatin.
  5. GSTA4 down-regulation and the concomitant increase in 4-hydroxynonenal adducts in muscle are indicative of susceptibility to infection in individuals with severe thermal injuries.
    Title: Down-regulation of glutatione S-transferase α 4 (hGSTA4) in the muscle of thermally injured patients is indicative of susceptibility to bacterial infection.
  6. Data show that mandatory overexpression of hGSTA4 by transient transfection in KYSE30 cells and attenuation of HNE-induced EGFR phosphorylation.
    Title: The balance between 4-hydroxynonenal and intrinsic glutathione/glutathione S-transferase A4 system may be critical for the epidermal growth factor receptor phosphorylation of human esophageal squamous cell carcinomas.
  7. analysis of four novel mutations that change the function of leukotriene C(4) synthase and are associated with increased risk of venous thromboembolism and ischemic stroke
    Title: Novel mutations in leukotriene C4 synthase and risk of cardiovascular disease based on genotypes from 50,000 individuals.
  8. Gsta4/GSTA4 is a novel susceptibility gene for NMSC that affects risk in both mice and humans.
    Title: Evidence that Gsta4 modifies susceptibility to skin tumor development in mice and humans.
  9. Results indicate that downregulation of GSTA4 in adipose tissue leads to increased protein carbonylation, ROS production, and mitochondrial dysfunction and may contribute to the development of insulin resistance and type 2 diabetes.
    Title: Downregulation of adipose glutathione S-transferase A4 leads to increased protein carbonylation, oxidative stress, and mitochondrial dysfunction.
  10. GSTA4-4 exploits the hydroxyl group of either 4R- or 4S-hydroxynonenal (HNE), while specifically binding HNE and glutathione (GSH) to maintain high catalytic efficiency linked with stereoselective product formation for both enantiomeric substrates.
    Title: Substrate specificity combined with stereopromiscuity in glutathione transferase A4-4-dependent metabolism of 4-hydroxynonenal.
Submit: New GeneRIF Correction See all GeneRIFs (24)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

EBI GWAS Catalog

Description
A genome-wide association study and biological pathway analysis of epilepsy prognosis in a prospective cohort of newly treated epilepsy.
EBI GWAS Catalog

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Genotypes

HIV-1 interactions

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Protein interactions

Protein Gene Interaction Pubs
Vif vif HIV-1 Vif downregulates the expression of glutathione S-transferase alpha 4 (GSTA4) in Vif-expression T cells PubMed

Go to the HIV-1, Human Interaction Database

Pathways from PubChem

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Interactions

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Products Interactant Other Gene Complex Source Pubs Description

General gene information

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Markers

Homology

Clone Names

  • DKFZp686D21185

Gene Ontology Provided by GOA

Function Evidence Code Pubs
enables glutathione transferase activity IBA
Inferred from Biological aspect of Ancestor
more info
  
enables glutathione transferase activity IDA
Inferred from Direct Assay
more info
 PubMed 
enables identical protein binding IPI
Inferred from Physical Interaction
more info
 PubMed 
enables protein binding IPI
Inferred from Physical Interaction
more info
 PubMed 
enables protein homodimerization activity IPI
Inferred from Physical Interaction
more info
 PubMed 
Process Evidence Code Pubs
involved_in glutathione metabolic process IBA
Inferred from Biological aspect of Ancestor
more info
  
involved_in glutathione metabolic process IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in xenobiotic metabolic process IBA
Inferred from Biological aspect of Ancestor
more info
  
involved_in xenobiotic metabolic process IDA
Inferred from Direct Assay
more info
 PubMed 
Component Evidence Code Pubs
located_in cytosol TAS
Traceable Author Statement
more info
  

General protein information

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Preferred Names
glutathione S-transferase A4
Names
GST class-alpha member 4
S-(hydroxyalkyl)glutathione lyase A4
glutathione S-alkyltransferase A4
glutathione S-aralkyltransferase A4
glutathione S-aryltransferase A4
glutathione S-transferase A4-4
glutathione transferase A4-4
NP_001503.1
XP_005249092.1
XP_011512836.1
XP_011512837.1
XP_054211236.1
XP_054211237.1
XP_054211238.1

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)

  1. NM_001512.4 → NP_001503.1  glutathione S-transferase A4

    See identical proteins and their annotated locations for NP_001503.1

    Status: REVIEWED

    Source sequence(s)
    AA709059, AK315369, BC063439, DA521337
    Consensus CDS
    CCDS4948.1
    UniProtKB/Swiss-Prot
    B2RD15, O15217, Q5T7Q8, Q6P4G1, Q9BX18, Q9H414
    Related
    ENSP00000360002.4, ENST00000370963.9
    Conserved Domains (2) summary
    cd03208
    Location:86 → 220
    GST_C_Alpha; C-terminal, alpha helical domain of Class Alpha Glutathione S-transferases
    cl00388
    Location:4 → 82
    Thioredoxin_like; Protein Disulfide Oxidoreductases and Other Proteins with a Thioredoxin fold

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2023_10

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

Reference GRCh38.p14 Primary Assembly

Genomic

  1. NC_000006.12 Reference GRCh38.p14 Primary Assembly

    Range
    52977953..52995284 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_011514534.4 → XP_011512836.1  glutathione S-transferase A4 isoform X2

    See identical proteins and their annotated locations for XP_011512836.1

    UniProtKB/TrEMBL
    B3KNR3
    Conserved Domains (2) summary
    cd03208
    Location:49 → 183
    GST_C_Alpha; C-terminal, alpha helical domain of Class Alpha Glutathione S-transferases
    cl00388
    Location:12 → 45
    Thioredoxin_like; Protein Disulfide Oxidoreductases and Other Proteins with a Thioredoxin fold

  2. XM_011514535.4 → XP_011512837.1  glutathione S-transferase A4 isoform X2

    See identical proteins and their annotated locations for XP_011512837.1

    UniProtKB/TrEMBL
    B3KNR3
    Conserved Domains (2) summary
    cd03208
    Location:49 → 183
    GST_C_Alpha; C-terminal, alpha helical domain of Class Alpha Glutathione S-transferases
    cl00388
    Location:12 → 45
    Thioredoxin_like; Protein Disulfide Oxidoreductases and Other Proteins with a Thioredoxin fold

  3. XM_005249035.5 → XP_005249092.1  glutathione S-transferase A4 isoform X1

    See identical proteins and their annotated locations for XP_005249092.1

    UniProtKB/Swiss-Prot
    B2RD15, O15217, Q5T7Q8, Q6P4G1, Q9BX18, Q9H414
    Conserved Domains (2) summary
    cd03208
    Location:86 → 220
    GST_C_Alpha; C-terminal, alpha helical domain of Class Alpha Glutathione S-transferases
    cl00388
    Location:4 → 82
    Thioredoxin_like; Protein Disulfide Oxidoreductases and Other Proteins with a Thioredoxin fold

Alternate T2T-CHM13v2.0

Genomic

  1. NC_060930.1 Alternate T2T-CHM13v2.0

    Range
    52817518..52834853 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_054355262.1 → XP_054211237.1  glutathione S-transferase A4 isoform X2

  2. XM_054355263.1 → XP_054211238.1  glutathione S-transferase A4 isoform X2

  3. XM_054355261.1 → XP_054211236.1  glutathione S-transferase A4 isoform X1

    UniProtKB/Swiss-Prot
    B2RD15, O15217, Q5T7Q8, Q6P4G1, Q9BX18, Q9H414
Nucleotide Protein
Heading Accession and Version
Protein Accession Links
GenPept Link UniProtKB Link
O15217.1 GenPept UniProtKB/Swiss-Prot:O15217

Gene LinkOut

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