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    GSTA3 glutathione S-transferase alpha 3 [ Homo sapiens (human) ]

    Gene ID: 2940, updated on 27-Nov-2024

    Summary

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    Official Symbol
    GSTA3provided by HGNC
    Official Full Name
    glutathione S-transferase alpha 3provided by HGNC
    Primary source
    HGNC:HGNC:4628
    See related
    Ensembl:ENSG00000174156 MIM:605449; AllianceGenome:HGNC:4628
    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
    GTA3; GSTA3-3
    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 genes that are located in a cluster mapped to chromosome 6. Genes of the alpha class are highly related and encode enzymes with glutathione peroxidase activity. However, during evolution, this alpha class gene diverged accumulating mutations in the active site that resulted in differences in substrate specificity and catalytic activity. The enzyme encoded by this gene catalyzes the double bond isomerization of precursors for progesterone and testosterone during the biosynthesis of steroid hormones. An additional transcript variant has been identified, but its full length sequence has not been determined. [provided by RefSeq, Jul 2008]
    Expression
    Biased expression in adrenal (RPKM 10.7), placenta (RPKM 5.5) and 2 other tissues See more
    Orthologs
    all
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    Genomic context

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    See GSTA3 in Genome Data Viewer
    Location:
    6p12.2
    Exon count:
    9
    Annotation release Status Assembly Chr Location
    RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 6 NC_000006.12 (52896646..52909698, complement)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 6 NC_060930.1 (52736167..52749210, complement)
    RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 6 NC_000006.11 (52761444..52774496, complement)

    Chromosome 6 - NC_000006.12Genomic Context describing neighboring genes Neighboring gene glutathione S-transferase alpha 11, pseudogene Neighboring gene Neanderthal introgressed variant-containing enhancer experimental_92153 Neighboring gene ReSE screen-validated silencer GRCh37_chr6:52734542-52734752 Neighboring gene uncharacterized LOC105375091 Neighboring gene Neanderthal introgressed variant-containing enhancer experimental_92154 Neighboring gene glutathione S-transferase alpha 10, pseudogene Neighboring gene H3K27ac hESC enhancer GRCh37_chr6:52774000-52774692 Neighboring gene H3K27ac hESC enhancer GRCh37_chr6:52774693-52775386 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 glutathione S-transferase alpha 4

    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. Inhibitory effect of glutathione S-transferase A3 in the progression of cutaneous squamous cell carcinoma. Li W, et al. J Cosmet Dermatol, 2021 Jul. PMID 33089654
    2. Human glutathione transferase A3-3, a highly efficient catalyst of double-bond isomerization in the biosynthetic pathway of steroid hormones. Johansson AS, et al. J Biol Chem, 2001 Aug 31. PMID 11418619
    3. Active-site residues governing high steroid isomerase activity in human glutathione transferase A3-3. Johansson AS, et al. J Biol Chem, 2002 May 10. PMID 11872752
    4. Functional polymorphism of human glutathione transferase A3: effects on xenobiotic metabolism and steroid biosynthesis. Tetlow N, et al. Pharmacogenetics, 2004 Oct. PMID 15454730
    5. The isomerization of Δ5-androstene-3,17-dione by the human glutathione transferase A3-3 proceeds via a conjugated heteroannular diene intermediate. Daka JL, et al. J Biol Chem, 2014 Nov 14. PMID 25248748, Free PMC Article

    See all (30) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. Inhibitory effect of glutathione S-transferase A3 in the progression of cutaneous squamous cell carcinoma.
      Title: Inhibitory effect of glutathione S-transferase A3 in the progression of cutaneous squamous cell carcinoma.
    2. Certain core genes, including COL12A1, glutathione Stransferase alpha3 (GSTA3), fibrinogen alpha chain (FGA) and fibrinogen gamma chain (FGG), were the first reported to be associated with Gastric Cancer. Survival analysis suggested that these four genes, COL12A1 (P=0.002), GSTA3 (P=3.4x106), FGA (P=0.00075) and FGG (P=1.4x105), were significant poor prognostic factors of gastric cancer.
      Title: Novel prognostic biomarkers of gastric cancer based on gene expression microarray: COL12A1, GSTA3, FGA and FGG.
    3. GSTA3 expression is significantly downregulated in human masticatory mucosa during wound healing
      Title: Human gingiva transcriptome during wound healing.
    4. Density functional theory calculations used to propose a refined mechanism for the isomerization of delta(5)-androstene-3,17-dione catalyzed by GST A3-3
      Title: Isomerization of Δ5-androstene-3,17-dione into Δ4-androstene-3,17-dione catalyzed by human glutathione transferase A3-3: a computational study identifies a dual role for glutathione.
    5. analysis of how isomerization of the steroid Delta(5)-androstene-3,17-dione by the glutathione transferase A3-3
      Title: The isomerization of Δ5-androstene-3,17-dione by the human glutathione transferase A3-3 proceeds via a conjugated heteroannular diene intermediate.
    6. 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.
    7. The 3D structures of human GSTs A2-2 and A3-3 in complex with Delta(4)-androstene-3-17-dione, were solved.
      Title: Structural basis for featuring of steroid isomerase activity in alpha class glutathione transferases.
    8. Observational study of gene-disease association. (HuGE Navigator)
      Title: New genetic associations detected in a host response study to hepatitis B vaccine.
    9. Significantly contributes to the double-bond isomerization necessary for steroid hormone biosynthesis in complex systems, thereby complementing the indispensable 3beta-hydroxysteroid oxidoreductase activity of 3beta-hydroxysteroid dehydrogenase.
      Title: Targeting human glutathione transferase A3-3 attenuates progesterone production in human steroidogenic cells.
    10. Analysis of the active centers of hGSTA3-3 reveals that residues in positions 12 and 208 may contribute to its disparate isomerase activity toward Delta(5)-AD.
      Title: Crystal structure of human glutathione S-transferase A3-3 and mechanistic implications for its high steroid isomerase activity.
    Submit: New GeneRIF Correction See all GeneRIFs (11)

    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

    Variation

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    See variants in ClinVar

    See studies and variants in dbVar

    See Variation Viewer (GRCh37.p13)

    See Variation Viewer (GRCh38)

    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

    • MGC22232

    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 ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    Process Evidence Code Pubs
    involved_in glutathione metabolic process IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in glutathione metabolic process ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    involved_in lipid metabolic process IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in xenobiotic metabolic process IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    Component Evidence Code Pubs
    is_active_in cytosol IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    located_in cytosol IDA
    Inferred from Direct Assay
    more info
    		  
    located_in cytosol TAS
    Traceable Author Statement
    more info
    		  
    located_in extracellular exosome HDA PubMed 

    General protein information

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    Preferred Names
    glutathione S-transferase A3
    Names
    GST class-alpha member 3
    S-(hydroxyalkyl)glutathione lyase A3
    glutathione S-alkyltransferase A3
    glutathione S-aralkyltransferase A3
    glutathione S-aryltransferase A3
    glutathione S-transferase A3-3
    NP_000838.3
    NP_001350471.1
    XP_006715135.1
    XP_011512835.1
    XP_047274641.1
    XP_054211233.1
    XP_054211234.1
    XP_054211235.1

    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_000847.5 → NP_000838.3  glutathione S-transferase A3 isoform 1

      See identical proteins and their annotated locations for NP_000838.3

      Status: REVIEWED

      Description
      Transcript Variant: This variant (1) represents the longer transcript and encodes the longer isoform (1).
      Source sequence(s)
      AI199811, AL121969, BC020619, DT932587
      Consensus CDS
      CCDS4947.1
      UniProtKB/Swiss-Prot
      O43468, Q068V6, Q16772, Q8WWA8, Q9H415
      Related
      ENSP00000211122.3, ENST00000211122.4
      Conserved Domains (2) summary
      cd03208
      Location:86 → 220
      GST_C_Alpha; C-terminal, alpha helical domain of Class Alpha Glutathione S-transferases
      cd03077
      Location:4 → 82
      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, ...

    2. NM_001363542.2 → NP_001350471.1  glutathione S-transferase A3 isoform 2

      Status: REVIEWED

      Description
      Transcript Variant: This variant (2) differs in the 5' UTR and coding sequence compared to variant 1. The resulting isoform (2) is shorter at the N-terminus compared to isoform 1.
      Source sequence(s)
      AF020919, AL121969
      Consensus CDS
      CCDS87412.1
      UniProtKB/TrEMBL
      Q5JW85
      Related
      ENSP00000360007.1, ENST00000370968.5
      Conserved Domains (2) summary
      cd03208
      Location:36 → 170
      GST_C_Alpha; C-terminal, alpha helical domain of Class Alpha Glutathione S-transferases
      cl00388
      Location:1 → 32
      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
      52896646..52909698 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_006715072.5 → XP_006715135.1  glutathione S-transferase A3 isoform X1

      See identical proteins and their annotated locations for XP_006715135.1

      UniProtKB/TrEMBL
      Q5JW85
      Conserved Domains (2) summary
      cd03208
      Location:36 → 170
      GST_C_Alpha; C-terminal, alpha helical domain of Class Alpha Glutathione S-transferases
      cl00388
      Location:1 → 32
      Thioredoxin_like; Protein Disulfide Oxidoreductases and Other Proteins with a Thioredoxin fold

    2. XM_047418685.1 → XP_047274641.1  glutathione S-transferase A3 isoform X1

      UniProtKB/TrEMBL
      Q5JW85

    3. XM_011514533.3 → XP_011512835.1  glutathione S-transferase A3 isoform X2

      Conserved Domains (1) summary
      cd03208
      Location:1 → 127
      GST_C_Alpha; C-terminal, alpha helical domain of Class Alpha Glutathione S-transferases

    RNA

    1. XR_926166.3 RNA Sequence

    2. XR_926167.3 RNA Sequence

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060930.1 Alternate T2T-CHM13v2.0

      Range
      52736167..52749210 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_054355259.1 → XP_054211234.1  glutathione S-transferase A3 isoform X1

      UniProtKB/TrEMBL
      Q5JW85

    2. XM_054355258.1 → XP_054211233.1  glutathione S-transferase A3 isoform X1

      UniProtKB/TrEMBL
      Q5JW85

    3. XM_054355260.1 → XP_054211235.1  glutathione S-transferase A3 isoform X2

    RNA

    1. XR_008487318.1 RNA Sequence

    2. XR_008487319.1 RNA Sequence

    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    Q16772.3 GenPept UniProtKB/Swiss-Prot:Q16772

    Gene LinkOut

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