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

Gene ID: 2940, updated on 5-Mar-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_2023_10 current GRCh38.p14 (GCF_000001405.40) 6 NC_000006.12 (52896646..52909698, complement)
RS_2023_10 current T2T-CHM13v2.0 (GCF_009914755.1) 6 NC_060930.1 (52736167..52749210, complement)
105.20220307 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. 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
  3. 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. Dourado DF, et al. J Phys Chem A, 2014 Aug 7. PMID 24739064
  4. Targeting human glutathione transferase A3-3 attenuates progesterone production in human steroidogenic cells. Raffalli-Mathieu F, et al. Biochem J, 2008 Aug 15. PMID 18426392
  5. Mutation analyses of genes on 6p12-p11 in patients with juvenile myoclonic epilepsy. Suzuki T, et al. Neurosci Lett, 2006 Sep 11. PMID 16876319

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)

Genotypes

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_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
    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

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