1. Gene Aliases

glutathione S-transferase pi 2, Gst3, Gst-3, GSTpiA

[https://www.ncbi.nlm.nih.gov/gene/14869]

Orthologous to human GSTP1 (glutathione S-transferase pi 1) gene [https://www.ncbi.nlm.nih.gov/gene/14869]

2. Association with Toxicity and/or Disease at a Transcriptional Level

3. Summary of Protein Family and Structure

4. Proteins Known to Interact with Gene Product

Interactions with experimental support

The interactions list has been truncated to include only interactions with the strongest support from the literature.

5. Links to Gene Databases

6. GO Terms, MSigDB Signatures, Pathways Containing Gene with Descriptions of Gene Sets

Pathways:

GO terms:

animal organ regeneration [The regrowth of a lost or destroyed animal organ. GO:0031100]

cellular oxidant detoxification [Any process carried out at the cellular level that reduces or removes the toxicity superoxide radicals or hydrogen peroxide. GO:0098869]

cellular response to cell-matrix adhesion [Any process that results in a change in state or activity of a cell (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of cell-matrix adhesion. GO:0071460]

cellular response to epidermal growth factor stimulus [Any process that results in a change in state or activity of a cell (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of an epidermal growth factor stimulus. GO:0071364]

cellular response to glucocorticoid stimulus [Any process that results in a change in state or activity of a cell (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of a glucocorticoid stimulus. Glucocorticoids are hormonal C21 corticosteroids synthesized from cholesterol with the ability to bind with the cortisol receptor and trigger similar effects. Glucocorticoids act primarily on carbohydrate and protein metabolism, and have anti-inflammatory effects. GO:0071385]

cellular response to insulin stimulus [Any process that results in a change in state or activity of a cell (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of an insulin stimulus. Insulin is a polypeptide hormone produced by the islets of Langerhans of the pancreas in mammals, and by the homologous organs of other organisms. GO:0032869]

cellular response to lipopolysaccharide [Any process that results in a change in state or activity of a cell (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of a lipopolysaccharide stimulus; lipopolysaccharide is a major component of the cell wall of gram-negative bacteria. GO:0071222]

common myeloid progenitor cell proliferation [The multiplication or reproduction of common myeloid progenitor cells, resulting in the expansion of a cell population. A common myeloid progenitor cell is a progenitor cell committed to the myeloid lineage. GO:0035726]

glutathione derivative biosynthetic process [The chemical reactions and pathways resulting in the formation of glutathione derivative. GO:1901687]

glutathione metabolic process [The chemical reactions and pathways involving glutathione, the tripeptide glutamylcysteinylglycine, which acts as a coenzyme for some enzymes and as an antioxidant in the protection of sulfhydryl groups in enzymes and other proteins; it has a specific role in the reduction of hydrogen peroxide (H2O2) and oxidized ascorbate, and it participates in the gamma-glutamyl cycle. GO:0006749]

hepoxilin biosynthetic process [The chemical reactions and pathways resulting in the formation of hepoxilins, a class of bioactive icosanoids with roles in the regulation of cell physiology. GO:0051122]

linoleic acid metabolic process [The chemical reactions and pathways involving linoleic acid, an unsaturated omega-6 fatty acid that has the molecular formula C18H32O2. GO:0043651]

negative regulation of ERK1 and ERK2 cascade [Any process that stops, prevents, or reduces the frequency, rate or extent of signal transduction mediated by the ERK1 and ERK2 cascade. GO:0070373]

negative regulation of biosynthetic process [Any process that stops, prevents, or reduces the rate of the chemical reactions and pathways resulting in the formation of substances. GO:0009890]

negative regulation of canonical NF-kappaB signal transduction [Any process that stops, prevents, or reduces the frequency, rate or extent of a canonical NF-kappaB signaling cascade. GO:0043124]

negative regulation of extrinsic apoptotic signaling pathway [Any process that stops, prevents or reduces the frequency, rate or extent of extrinsic apoptotic signaling pathway. GO:2001237]

negative regulation of fibroblast proliferation [Any process that stops, prevents, or reduces the frequency, rate or extent of multiplication or reproduction of fibroblast cells. GO:0048147]

negative regulation of interleukin-1 beta production [Any process that stops, prevents, or reduces the frequency, rate, or extent of interleukin-1 beta production. GO:0032691]

negative regulation of leukocyte proliferation [Any process that stops, prevents, or reduces the frequency, rate or extent of leukocyte proliferation. GO:0070664]

negative regulation of monocyte chemotactic protein-1 production [Any process that stops, prevents, or reduces the frequency, rate, or extent of production of monocyte chemotactic protein-1. GO:0071638]

negative regulation of nitric-oxide synthase biosynthetic process [Any process that stops, prevents, or reduces the frequency, rate or extent of the chemical reactions and pathways resulting in the formation of a nitric-oxide synthase enzyme. GO:0051771]

negative regulation of protein kinase activity [Any process that stops, prevents, or reduces the frequency, rate or extent of protein kinase activity. GO:0006469]

negative regulation of smooth muscle cell chemotaxis [Any process that stops, prevents, or reduces the frequency, rate, or extent of smooth muscle cell chemotaxis. GO:0071672]

negative regulation of stress-activated MAPK cascade [Any process that stops, prevents, or reduces the frequency, rate or extent of signal transduction mediated by the stress-activated MAPK cascade. GO:0032873]

negative regulation of tumor necrosis factor production [Any process that stops, prevents, or reduces the frequency, rate, or extent of tumor necrosis factor production.|Note that this term refers only to the specific, original 'tumor necrosis factor' protein (TNF) and not other members of the tumor necrosis factor superfamily (those with the gene symbol root 'TNFSF'). GO:0032720]

negative regulation of vascular associated smooth muscle cell proliferation [Any process that stops, prevents or reduces the frequency, rate or extent of vascular smooth muscle cell proliferation. GO:1904706]

oligodendrocyte development [The process aimed at the progression of an oligodendrocyte over time, from initial commitment of the cell to a specific fate, to the fully functional differentiated cell. An oligodendrocyte is a type of glial cell involved in myelinating the axons in the central nervous system. GO:0014003]

positive regulation of superoxide anion generation [Any process that activates or increases the frequency, rate or extent of enzymatic generation of superoxide by a cell. GO:0032930]

prostaglandin metabolic process [The chemical reactions and pathways involving prostaglandins, any of a group of biologically active metabolites which contain a cyclopentane ring due to the formation of a bond between two carbons of a fatty acid. They have a wide range of biological activities. GO:0006693]

regulation of ERK1 and ERK2 cascade [Any process that modulates the frequency, rate or extent of signal transduction mediated by the ERK1 and ERK2 cascade. GO:0070372]

regulation of stress-activated MAPK cascade [Any process that modulates the frequency, rate or extent of signal transduction mediated by the stress-activated MAPK cascade. GO:0032872]

response to L-ascorbic acid [Any process that results in a change in state or activity of a cell or an organism (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of an L-ascorbic acid (vitamin C) stimulus. GO:0033591]

response to amino acid [Any process that results in a change in state or activity of a cell or an organism (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of an amino acid stimulus. An amino acid is a carboxylic acids containing one or more amino groups. GO:0043200]

response to estradiol [Any process that results in a change in state or activity of a cell or an organism (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of stimulus by estradiol, a C18 steroid hormone hydroxylated at C3 and C17 that acts as a potent estrogen. GO:0032355]

response to ethanol [Any process that results in a change in state or activity of a cell or an organism (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of an ethanol stimulus. GO:0045471]

response to nutrient levels [Any process that results in a change in state or activity of a cell or an organism (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of a stimulus reflecting the presence, absence, or concentration of nutrients. GO:0031667]

response to reactive oxygen species [Any process that results in a change in state or activity of a cell or an organism (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of a reactive oxygen species stimulus. Reactive oxygen species include singlet oxygen, superoxide, and oxygen free radicals. GO:0000302]

response to toxic substance [Any process that results in a change in state or activity of a cell or an organism (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of a toxic stimulus. GO:0009636]

xenobiotic metabolic process [The chemical reactions and pathways involving a xenobiotic compound, a compound foreign to the organism exposed to it. It may be synthesized by another organism (like ampicillin) or it can be a synthetic chemical. GO:0006805]

MSigDB Signatures:

WP_NUCLEAR_RECEPTORS_META_PATHWAY: Nuclear receptors meta pathway [https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/WP_NUCLEAR_RECEPTORS_META_PATHWAY.html]

REACTOME_INNATE_IMMUNE_SYSTEM: Innate Immune System [https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/REACTOME_INNATE_IMMUNE_SYSTEM.html]

KEGG_GLUTATHIONE_METABOLISM: Glutathione metabolism [https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/KEGG_GLUTATHIONE_METABOLISM.html]

REACTOME_CELLULAR_RESPONSES_TO_STIMULI: Cellular responses to stimuli [https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/REACTOME_CELLULAR_RESPONSES_TO_STIMULI.html]

KEGG_PATHWAYS_IN_CANCER: Pathways in cancer [https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/KEGG_PATHWAYS_IN_CANCER.html]

KEGG_PROSTATE_CANCER: Prostate cancer [https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/KEGG_PROSTATE_CANCER.html]

RIEGE_DELTANP63_DIRECT_TARGETS_UP: Genes directly up-regulated by DeltaNp63, the p63 isoform that lacks the canonical transactivation domain and is predominantly expressed in stratifying epithelia, identified through a meta-analysis of both cell lines and primary cells. [https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/RIEGE_DELTANP63_DIRECT_TARGETS_UP.html]

REACTOME_CELLULAR_RESPONSE_TO_CHEMICAL_STRESS: Cellular response to chemical stress [https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/REACTOME_CELLULAR_RESPONSE_TO_CHEMICAL_STRESS.html]

KEGG_MEDICUS_ENV_FACTOR_TCDD_TO_AHR_SIGNALING_PATHWAY: Pathway Definition from KEGG: TCDD -> (AHR+ARNT) => (CYP1A1,CYP1B1,GST) [https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/KEGG_MEDICUS_ENV_FACTOR_TCDD_TO_AHR_SIGNALING_PATHWAY.html]

REACTOME_BIOLOGICAL_OXIDATIONS: Biological oxidations [https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/REACTOME_BIOLOGICAL_OXIDATIONS.html]

WP_METAPATHWAY_BIOTRANSFORMATION_PHASE_I_AND_II: Metapathway biotransformation Phase I and II [https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/WP_METAPATHWAY_BIOTRANSFORMATION_PHASE_I_AND_II.html]

KEGG_METABOLISM_OF_XENOBIOTICS_BY_CYTOCHROME_P450: Metabolism of xenobiotics by cytochrome P450 [https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/KEGG_METABOLISM_OF_XENOBIOTICS_BY_CYTOCHROME_P450.html]

KEGG_MEDICUS_REFERENCE_KEAP1_NRF2_SIGNALING_PATHWAY: Pathway Definition from KEGG: (O2-,HO2,H2O2,OH,ACRL,4HNE,NO) -| KEAP1 -| NRF2 => (HMOX1,NQO1,GST,TXNRD1) [https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/KEGG_MEDICUS_REFERENCE_KEAP1_NRF2_SIGNALING_PATHWAY.html]

REACTOME_GLUTATHIONE_CONJUGATION: Glutathione conjugation [https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/REACTOME_GLUTATHIONE_CONJUGATION.html]

REACTOME_DRUG_ADME: Drug ADME [https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/REACTOME_DRUG_ADME.html]

KEGG_MEDICUS_ENV_FACTOR_DCE_TO_DNA_ADDUCTS: Pathway Definition from KEGG: DCE -- GST -> C20304 -> C14874 == DNA [https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/KEGG_MEDICUS_ENV_FACTOR_DCE_TO_DNA_ADDUCTS.html]

REACTOME_DETOXIFICATION_OF_REACTIVE_OXYGEN_SPECIES: Detoxification of Reactive Oxygen Species [https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/REACTOME_DETOXIFICATION_OF_REACTIVE_OXYGEN_SPECIES.html]

REACTOME_PHASE_II_CONJUGATION_OF_COMPOUNDS: Phase II - Conjugation of compounds [https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/REACTOME_PHASE_II_CONJUGATION_OF_COMPOUNDS.html]

7. Gene Descriptions

NCBI Gene Summary: Glutathione S-transferases (GSTs) are a family of enzymes that play an important role in detoxification by catalyzing the conjugation of many hydrophobic and electrophilic compounds with reduced glutathione. Based on their biochemical, immunologic, and structural properties, the soluble GSTs are categorized into 4 main classes: alpha, mu, pi, and theta. This GST family member is a polymorphic gene encoding active, functionally different GSTP1 variant proteins that are thought to function in xenobiotic metabolism and play a role in susceptibility to cancer, and other diseases.

GeneCards Summary: GSTP1 (Glutathione S-Transferase Pi 1) is a Protein Coding gene. Diseases associated with GSTP1 include Kala-Azar 2 and Larynx Cancer. Among its related pathways are Metapathway biotransformation Phase I and II and Innate Immune System. Gene Ontology (GO) annotations related to this gene include glutathione transferase activity and kinase regulator activity. An important paralog of this gene is GSTA3.

UniProtKB/Swiss-Prot Summary: Conjugation of reduced glutathione to a wide number of exogenous and endogenous hydrophobic electrophiles. Involved in the formation of glutathione conjugates of both prostaglandin A2 (PGA2) and prostaglandin J2 (PGJ2) [PMID: 9084911]. Participates in the formation of novel hepoxilin regioisomers [PMID: 21046276]. Regulates negatively CDK5 activity via p25/p35 translocation to prevent neurodegeneration.

8. Cellular Location of Gene Product

Cytoplasmic expression in most tissues. Localized to the cytosol & mitochondria. Predicted location: Intracellular [https://www.proteinatlas.org/ENSG00000084207/subcellular]

9. Mechanistic Information

Summary

The Gstp2 gene, encoding the Glutathione S-Transferase Pi 2 (GSTP2) enzyme, is upregulated in response to thyroid toxicity, as seen with substances like NaI, PB, and PTU [CS: 6]. This upregulation is a direct biochemical response to the increased presence of toxic compounds [CS: 5]. GSTP2 functions by catalyzing the conjugation of glutathione to various hydrophobic and electrophilic compounds [CS: 10]. In the context of thyroid toxicity, this activity aids in detoxifying harmful substances that may accumulate [CS: 7]. For example, PB (phenobarbital) induces oxidative stress, and the increased expression of GSTP2 provides a means to mitigate this stress by enhancing the detoxification of reactive oxidative species [CS: 7].

Furthermore, GSTP2's role extends beyond simple detoxification [CS: 7]. It's involved in the regulation of various cellular pathways that are crucial during stress responses [CS: 8]. In the case of thyroid toxicity, where cellular homeostasis is disrupted, the upregulation of Gstp2 likely helps in maintaining cellular integrity [CS: 6]. This is achieved through the enzyme's secondary functions, such as regulating kinase activities, which are vital in cell signaling and stress responses [CS: 8]. For instance, GSTP2's ability to inhibit c-Jun NH2-terminal kinase (JNK) could be crucial in preventing cellular damage under toxic stress, as JNK is known to be involved in apoptotic pathways [CS: 7].

10. Upstream Regulators

11. Tissues/Cell Type Where Genes are Overexpressed

Tissue type enchanced: choroid plexus (tissue enhanced) [https://www.proteinatlas.org/ENSG00000084207/tissue]

Cell type enchanced: proximal tubular cells, squamous epithelial cells, suprabasal keratinocytes (cell type enhanced) [https://www.proteinatlas.org/ENSG00000084207/single+cell+type]

12. Role of Gene in Other Tissues

13. Chemicals Known to Elicit Transcriptional Response of Biomarker in Tissue of Interest

Compounds that increase expression of the gene:

Compounds that decrease expression of the gene:

14. DisGeNet Biomarker Associations to Disease in Organ of Interest