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

    Gene ID: 2941, updated on 2-Nov-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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    See GSTA4 in Genome Data Viewer
    Location:
    6p12.2
    Exon count:
    7
    Annotation release Status Assembly Chr Location
    RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 6 NC_000006.12 (52977953..52995284, complement)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 6 NC_060930.1 (52817518..52834853, complement)
    RS_2024_09 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 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. 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, et al. Biochem J, 1998 Feb 15. PMID 9461507, Free PMC Article
    2. Depletion of 4-hydroxynonenal in hGSTA4-transfected HLE B-3 cells results in profound changes in gene expression. Patrick B, et al. Biochem Biophys Res Commun, 2005 Aug 26. PMID 16005854
    3. Molecular implications of the human glutathione transferase A-4 gene (hGSTA4) polymorphisms in neurodegenerative diseases. Coppedè F, et al. Mutat Res, 2005 Nov 11. PMID 16054170
    4. 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
    5. Glutathione-S-transferase protects against oxidative injury of endothelial cell tight junctions. Xu Y, et al. Endothelium, 2007 Nov-Dec. PMID 18080870

    See all (68) 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 IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    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_2024_08

    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

    The following LinkOut resources are supplied by external providers. These providers are responsible for maintaining the links.

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