Details for: GSTA2

Gene ID: 2939

Gene Type:  Protein-coding  - A gene that serves as a template for producing a messenger RNA (mRNA) molecule, which is then translated into a functional protein.

Symbol: GSTA2

Ensembl ID: ENSG00000244067

Description: glutathione S-transferase alpha 2

Selected Context(s):  Overall

Cell Significance Landscape

Contexts:

Associated with

Significant Cells

Cell Significance Index (CSI) scores for the chosen context(s)

  • pancreatic acinar cell CL0002064
    CSI 12.71
    rCSI 16.9%
    PRS 96.36
  • intestinal epithelial cell CL0002563
    CSI 9.19
    rCSI 9.6%
    PRS 92.98
  • epithelial cell of lower respiratory tract CL0002632
    CSI 6.32
    rCSI 4.9%
    PRS 96.36
  • intestine goblet cell CL0019031
    CSI 5.5
    rCSI 4.88%
    PRS 92.96
  • paneth cell CL0000510
    CSI 5.42
    rCSI 8%
    PRS 97.34
  • lung ciliated cell CL1000271
    CSI 5.22
    rCSI 6.04%
    PRS 90.89
  • secretory cell CL0000151
    CSI 4.88
    rCSI 5.09%
    PRS 94
  • acinar cell CL0000622
    CSI 4.61
    rCSI 6.76%
    PRS 97.47
  • colonocyte CL1000347
    CSI 4.54
    rCSI 6.51%
    PRS 93.18
  • epithelial cell of proximal tubule CL0002306
    CSI 4.33
    rCSI 10.57%
    PRS 90.12
  • ciliated columnar cell of tracheobronchial tree CL0002145
    CSI 4.31
    rCSI 9.82%
    PRS 88.95
  • enterocyte CL0000584
    CSI 4.1
    rCSI 6.61%
    PRS 92.1
  • ciliated cell CL0000064
    CSI 3.99
    rCSI 6.47%
    PRS 89.65
  • colon epithelial cell CL0011108
    CSI 3.65
    rCSI 3.82%
    PRS 92.95
  • hepatic stellate cell CL0000632
    CSI 3.65
    rCSI 13.66%
    PRS 92.42
  • myofibroblast cell CL0000186
    CSI 3.4
    rCSI 4.71%
    PRS 92.62
  • enteroendocrine cell CL0000164
    CSI 3.3
    rCSI 4.51%
    PRS 92.96
  • duct epithelial cell CL0000068
    CSI 3.29
    rCSI 4.82%
    PRS 96.84
  • intrahepatic cholangiocyte CL0002538
    CSI 3.1
    rCSI 7.43%
    PRS 94.28
  • foveolar cell of stomach CL0002179
    CSI 3.09
    rCSI 6.58%
    PRS 95.83
  • hepatocyte CL0000182
    CSI 2.92
    rCSI 5.22%
    PRS 93.29
  • nasal mucosa goblet cell CL0002480
    CSI 2.66
    rCSI 3.09%
    PRS 94.47
  • intestinal crypt stem cell of small intestine CL0009017
    CSI 2.61
    rCSI 7.03%
    PRS 95.78
  • transit amplifying cell CL0009010
    CSI 2.52
    rCSI 3.86%
    PRS 96.42
  • squamous epithelial cell CL0000076
    CSI 2.35
    rCSI 5.58%
    PRS 91.52
  • centrilobular region hepatocyte CL0019029
    CSI 2.2
    rCSI 5.74%
    PRS 91.06
  • multi-ciliated epithelial cell CL0005012
    CSI 2.06
    rCSI 2.06%
    PRS 90.5
  • pancreatic ductal cell CL0002079
    CSI 1.96
    rCSI 3.81%
    PRS 95.48
  • deuterosomal cell CL4033044
    CSI 1.16
    rCSI 3.93%
    PRS 89.65
  • bronchial goblet cell CL1000312
    CSI 1.16
    rCSI 4.63%
    PRS 96.55
  • enterocyte of epithelium of small intestine CL1000334
    CSI 0.5
    rCSI 7.78%
    PRS 95.42
  • respiratory goblet cell CL0002370
    CSI 0.34
    rCSI 3.71%
    PRS 96.39

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this specific cell.

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this cell type. Calculated using techniques like effect size estimation and bootstrapping for reliability.

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this cell type. Calculated using techniques like effect size estimation and bootstrapping for reliability.
Network Configuration

Explore relationships of the current gene. Select an Interaction Source: 'ONTOLOGY' for shared pathways (GO/Reactome) or 'STRING' for protein-protein interactions. Further refine by selecting context genes and comparing Cell Significance Index (CSI) scores between baseline and target cell types and their specific contexts.

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Legend:
  • Query Gene
  • Node Color (Target Cell CSI, relative to current network):
    • Very High
    • High
    • Medium
    • Low
    • Very Low
    • CSI N/A
  • Node Size: Proportional to Target Cell CSI magnitude
  • STRING PPI Edge
  • Shared Pathway Edge (ONTOLOGY)

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Other Information

This section provides additional information about the gene, including a description generated by an AI language model and details about associated proteins.

## Summary [GSTA2](/details-gene/2939) (Glutathione S-Transferase Alpha 2) is a protein-coding gene located on chromosome 6p12.2. It encodes a member of the alpha-class glutathione S-transferase (GST) family of enzymes, which play a central role in cellular detoxification. These enzymes catalyze the conjugation of reduced glutathione to a wide range of endogenous and exogenous electrophilic compounds, rendering them more water-soluble and facilitating their excretion. Consistent with this function, [GSTA2](/details-gene/2939) shows its highest significance in metabolically active and barrier epithelial tissues. **Overall**, it is a key marker for [pancreatic acinar cells](/details-cell/CL0002064) and various [intestinal epithelial cells](/details-cell/CL0002563), suggesting a primary role in protecting these tissues from metabolic and xenobiotic stress. Its activity is clinically relevant, as it is implicated in the metabolism of various drugs and associated with OMIM entry [138360](https://omim.org/entry/138360). ## Cellular Roles and Expression Landscape The expression profile of [GSTA2](/details-gene/2939) highlights its specialized function in tissues responsible for secretion, absorption, and detoxification. **Overall**, the gene's significance is most pronounced in glandular and epithelial cell types. It is the top marker in [pancreatic acinar cells](/details-cell/CL0002064) (CSI: 12.71), which are responsible for producing and secreting large quantities of digestive enzymes and are thus under high metabolic stress. Following this, [GSTA2](/details-gene/2939) is highly significant across the gastrointestinal tract, with strong expression in [intestinal epithelial cells](/details-cell/CL0002563), [intestine goblet cells](/details-cell/CL0019031), [Paneth cells](/details-cell/CL0000510), [colonocytes](/details-cell/CL1000347), and [enterocytes](/details-cell/CL0000584). This pattern underscores its critical role in defending the intestinal barrier against ingested toxins and microbial byproducts. Furthermore, its high significance in cell types of the respiratory system, such as [epithelial cells of the lower respiratory tract](/details-cell/CL0002632) and [lung ciliated cells](/details-cell/CL1000271), is consistent with a protective role at the air-liquid interface. The gene is also a notable marker for [epithelial cells of the proximal tubule](/details-cell/CL0002306) in the kidney and [hepatic stellate cells](/details-cell/CL0000632) in the liver, two other major sites of detoxification and metabolism. The collective expression data firmly establishes [GSTA2](/details-gene/2939) as a key enzyme in the cytoprotective machinery of secretory and barrier tissues. ## Pathways and Molecular Function The functional annotations for [GSTA2](/details-gene/2939) align directly with its cellular expression profile, centering on metabolic and detoxification processes. Its primary molecular function is [glutathione transferase activity](/details-go/GO:0004364), and it is a key component of the [glutathione metabolic process](/details-go/GO:0006749). The gene is a central player in Phase II biotransformation reactions, as indicated by its involvement in Reactome pathways such as [Glutathione conjugation](/details-pathway/R-HSA-156590), [Phase ii - conjugation of compounds](/details-pathway/R-HSA-156580), and the broader [Xenobiotic metabolic process](/details-go/GO:0006805). This enzymatic activity is crucial for neutralizing a wide array of harmful substances and is essential for pharmacokinetics, as highlighted by its role in [Drug adme](/details-pathway/R-HSA-9748784) and specifically [Azathioprine adme](/details-pathway/R-HSA-9748787). Interestingly, [GSTA2](/details-gene/2939) is also associated with immune signaling pathways, including [Cytokine signaling in immune system](/details-pathway/R-HSA-1280215) and [Interleukin-12 signaling](/details-pathway/R-HSA-9020591). While its expression is not prominent in canonical immune cells, this suggests a potential role in modulating inflammatory responses within the epithelial tissues where it resides, possibly by regulating redox-sensitive signaling cascades or metabolizing inflammatory byproducts. The protein is primarily localized to the [cytosol](/details-go/GO:0005829), where it performs its enzymatic functions, though its presence has also been noted in the [extracellular exosome](/details-go/GO:0070062). ## Research Directions The specific expression pattern and established function of [GSTA2](/details-gene/2939) suggest several avenues for future research into its role in tissue homeostasis and disease. **Proposed Hypotheses:** 1. Given its high expression in the intestinal epithelium ([intestinal epithelial cell](/details-cell/CL0002563), [colonocyte](/details-cell/CL1000347)) and its detoxification role, we hypothesize that **[GSTA2](/details-gene/2939) is a critical component of the gut barrier defense system, and its downregulation or dysfunction contributes to the pathogenesis of inflammatory bowel disease (IBD) by increasing susceptibility to luminal toxins and oxidative stress.** 2. The exceptional significance of [GSTA2](/details-gene/2939) in [pancreatic acinar cells](/details-cell/CL0002064) suggests a second hypothesis: **[GSTA2](/details-gene/2939) plays an essential protective role against premature digestive enzyme activation and cellular damage in the pancreas by neutralizing reactive oxygen species generated during high metabolic activity. Loss of function could be a predisposing factor for pancreatitis.** 3. The annotation linking [GSTA2](/details-gene/2939) to [Interleukin-12 signaling](/details-pathway/R-HSA-9020591) raises the possibility that **it modulates inflammatory signaling within epithelial cells by altering the local redox environment, thereby influencing the magnitude or duration of STAT phosphorylation downstream of cytokine receptors.** **Experimental Approach:** To test the first hypothesis regarding the role of [GSTA2](/details-gene/2939) in IBD, a knockout mouse model (`Gsta2`-/-) would be instrumental. These mice and their wild-type littermates could be subjected to a dextran sulfate sodium (DSS)-induced colitis model. The hypothesis would be supported if the `Gsta2`-/- mice exhibit more severe clinical symptoms (weight loss, bleeding), increased intestinal permeability (e.g., via FITC-dextran assay), exaggerated histological damage, and elevated expression of pro-inflammatory cytokines in the colonic tissue compared to wild-type controls. Further mechanistic insight could be gained by studying intestinal organoids derived from these mice to assess their intrinsic vulnerability to oxidative or toxic insults. **Therapeutic Potential:** As an intracellular enzyme involved in drug metabolism, [GSTA2](/details-gene/2939) is a prime candidate for study in pharmacogenomics and as a modulator of therapy rather than a direct target itself. Overexpression of GSTs is a known mechanism of resistance to chemotherapy in various cancers. Therefore, **inhibition** of [GSTA2](/details-gene/2939) could represent a valuable co-therapeutic strategy to sensitize tumors to alkylating agents and other electrophilic drugs. Conversely, strategies to **activate** or induce [GSTA2](/details-gene/2939) could be explored as a cytoprotective approach in conditions characterized by high oxidative stress or toxin exposure, such as drug-induced liver injury or certain inflammatory conditions.

Genular Protein ID: 647527921

Symbol: GSTA2_HUMAN

Name: Glutathione S-transferase A2

UniProtKB Accession Codes:

P09210 Q12759 Q16491 Q9NTY6

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 BRENDA 1 Bgee 1 BindingDB 1 BioCyc 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 1 CDD 2 CTD 1 ChEBI 9 ChEMBL 1 ChiTaRS 1 DMDM 1 DNASU 1 DisGeNET 1 DrugBank 13 EC 1 EMBL 15 Ensembl 1 EvolutionaryTrace 1 ExpressionAtlas 1 GO 6 Gene3D 2 GeneCards 1 GeneTree 1 GeneWiki 1 GenomeRNAi 1 GlyGen 1 HGNC 1 HOGENOM 1 HPA 1 InParanoid 1 IntAct 1 InterPro 8 KEGG 1 MANE-Select 1 MIM 1 MassIVE 1 NCBI Taxonomy 1 OMA 1 OpenTargets 1 OrthoDB 1 PANTHER 2 PDB 4 PDBsum 4 PIR 2 PRINTS 1 PRO 1 PROSITE 2 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 2 PharmGKB 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 1 REPRODUCTION-2DPAGE 1 RNAct 1 Reactome 3 RefSeq 2 Rhea 2 SABIO-RK 1 SFLD 2 SMR 1 STRING 1 SUPFAM 2 SignaLink 1 TreeFam 1 UCSC 1 VEuPathDB 1 eggNOG 1 iPTMnet 1 jPOST 1 neXtProt 1

Citations:

PubMed ID: 3036131

Title: The basic glutathione S-transferases from human livers are products of separate genes.

PubMed ID: 3036131

DOI: 10.1016/0006-291x(87)91345-3

PubMed ID: 1329668

Title: Isolation and characterization of the human glutathione S-transferase A2 subunit gene.

PubMed ID: 1329668

DOI: 10.1016/0003-9861(92)90475-c

PubMed ID: 1497629

Title: Cloning, sequencing and characterization of the human alpha glutathione S-transferase gene corresponding to the cDNA clone pGTH2.

PubMed ID: 1497629

DOI: 10.1042/bj2850925

PubMed ID: 14574404

Title: The DNA sequence and analysis of human chromosome 6.

PubMed ID: 14574404

DOI: 10.1038/nature02055

PubMed ID: 15489334

Title: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).

PubMed ID: 15489334

DOI: 10.1101/gr.2596504

PubMed ID: 8431482

Title: Characterization of two novel subunits of the alpha-class glutathione S-transferases of human liver.

PubMed ID: 8431482

DOI: 10.1016/0167-4838(93)90234-i

PubMed ID: 2604726

Title: Evidence that glutathione S-transferases B1B1 and B2B2 are the products of separate genes and that their expression in human liver is subject to inter-individual variation. Molecular relationships between the B1 and B2 subunits and other alpha class glutathione S-transferases.

PubMed ID: 2604726

DOI: 10.1042/bj2640437

PubMed ID: 7892174

Title: A surface mutant (G82R) of a human alpha-glutathione S-transferase shows decreased thermal stability and a new mode of molecular association in the crystal.

PubMed ID: 7892174

DOI: 10.1002/prot.340200306

PubMed ID: 20083122

Title: Structural basis for featuring of steroid isomerase activity in alpha class glutathione transferases.

PubMed ID: 20083122

DOI: 10.1016/j.jmb.2010.01.023

PubMed ID: 11668220

Title: Polymorphism of human alpha class glutathione transferases.

PubMed ID: 11668220

DOI: 10.1097/00008571-200110000-00007

PubMed ID: 24275569

Title: An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome.

PubMed ID: 24275569

DOI: 10.1016/j.jprot.2013.11.014

Sequence Information:

  • Length: 222
  • Mass: 25664
  • Checksum: 2823565A693A30AC
  • Sequence:
    • MAEKPKLHYS NIRGRMESIR WLLAAAGVEF EEKFIKSAED LDKLRNDGYL MFQQVPMVEI 
DGMKLVQTRA ILNYIASKYN LYGKDIKEKA LIDMYIEGIA DLGEMILLLP FSQPEEQDAK 
LALIQEKTKN RYFPAFEKVL KSHGQDYLVG NKLSRADIHL VELLYYVEEL DSSLISSFPL 
LKALKTRISN LPTVKKFLQP GSPRKPPMDE KSLEESRKIF RF

Genular Protein ID: 1982297815

Symbol: A8K987_HUMAN

Name: N/A

UniProtKB Accession Codes:

A8K987

Database IDs:

ARBA 3 AlphaFoldDB 1 BioGRID-ORCS 1 CDD 2 CTD 1 ChEBI 5 DNASU 1 DisGeNET 1 EC 1 EMBL 2 GO 4 Gene3D 2 InterPro 8 KEGG 1 NCBI Taxonomy 1 OrthoDB 1 PANTHER 2 PRINTS 1 PROSITE 4 PeptideAtlas 1 Pfam 2 PharmGKB 1 RefSeq 1 Rhea 1 RuleBase 1 SAM 1 SFLD 2 SMR 1 SUPFAM 2

Sequence Information:

  • Length: 222
  • Mass: 25677
  • Checksum: 782D585A6C6F6CBC
  • Sequence:
    • MAEKPKLHYS NIRGRMESIR WLLAAAGVEF EEKFIKSAED LDKLRNDGYL MFQQVPMVEI 
DGMKLVQTRA ILNYIASKYN LYGKDIKEKA LIDMYIEGIA DLGEMILLLP FTQPEEQDAK 
LALIQEKTKN RYFPAFEKVL KSHGQDYLVG NKLSRADIHL VELLYYVKEL DSSLISSFPL 
LKALKTRISN LPTVKKFLQP GSPRKPPMDE KSLEESRKIF RF