1. Gene Aliases

Metallothionein 2A, MT2, Metallothionein-II, Metallothionein-2, MT-II, MT-2, Metallothionein-2A, CES1

[https://www.genecards.org/cgi-bin/carddisp.pl?gene=MT2A]

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

Interactions with text mining support

5. Links to Gene Databases

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

Pathways:

GO terms:

astrocyte activation [A change in morphology and behavior of an astrocyte resulting from exposure to a cytokine, chemokine, cellular ligand, or soluble factor. GO:0048143]

cellular response to cadmium ion [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 cadmium (Cd) ion stimulus. GO:0071276]

cellular response to copper ion [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 copper ion stimulus. GO:0071280]

cellular response to erythropoietin [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 erythropoietin stimulus. GO:0036018]

cellular response to interleukin-3 [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 interleukin-3 stimulus. GO:0036016]

cellular response to zinc ion [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 zinc ion stimulus. GO:0071294]

detoxification of copper ion [Any process that reduces or removes the toxicity of copper ion. These include transport of copper away from sensitive areas and to compartments or complexes whose purpose is sequestration of copper ion. GO:0010273]

intracellular zinc ion homeostasis [A homeostatic process involved in the maintenance of a steady state level of zinc ions within a cell. GO:0006882]

negative regulation of growth [Any process that stops, prevents or reduces the rate or extent of growth, the increase in size or mass of all or part of an organism. GO:0045926]

nitric oxide mediated signal transduction [Any intracellular signal transduction in which the signal is passed on within the cell via nitric oxide (NO). Includes synthesis of nitric oxide, receptors/sensors for nitric oxide (such as soluble guanylyl cyclase/sGC) and downstream effectors that further transmit the signal within the cell. Nitric oxide transmits its downstream effects through either cyclic GMP (cGMP)-dependent or independent mechanisms. GO:0007263]

response to bacterium [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 from a bacterium. GO:0009617]

MSigDB Signatures:

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

WP_LUNG_FIBROSIS: Lung fibrosis [https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/WP_LUNG_FIBROSIS.html]

REACTOME_METALLOTHIONEINS_BIND_METALS: Metallothioneins bind metals [https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/REACTOME_METALLOTHIONEINS_BIND_METALS.html]

WP_ZINC_HOMEOSTASIS: Zinc homeostasis [https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/WP_ZINC_HOMEOSTASIS.html]

MA_RAT_AGING_UP: Genes up-regulated across multiple cell types from nine tissues during rat aging. [https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/MA_RAT_AGING_UP.html]

REACTOME_INTERFERON_SIGNALING: Interferon Signaling [https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/REACTOME_INTERFERON_SIGNALING.html]

WP_COPPER_HOMEOSTASIS: Copper homeostasis [https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/WP_COPPER_HOMEOSTASIS.html]

REACTOME_RESPONSE_TO_METAL_IONS: Response to metal ions [https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/REACTOME_RESPONSE_TO_METAL_IONS.html]

REACTOME_CYTOKINE_SIGNALING_IN_IMMUNE_SYSTEM: Cytokine Signaling in Immune system [https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/REACTOME_CYTOKINE_SIGNALING_IN_IMMUNE_SYSTEM.html]

REACTOME_INTERFERON_GAMMA_SIGNALING: Interferon gamma signaling [https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/REACTOME_INTERFERON_GAMMA_SIGNALING.html]

7. Gene Descriptions

NCBI Gene Summary: This gene is a member of the metallothionein family of genes. Proteins encoded by this gene family are low in molecular weight, are cysteine-rich, lack aromatic residues, and bind divalent heavy metal ions, altering the intracellular concentration of heavy metals in the cell. These proteins act as anti-oxidants, protect against hydroxyl free radicals, are important in homeostatic control of metal in the cell, and play a role in detoxification of heavy metals. The encoded protein interacts with the protein encoded by the homeobox containing 1 gene in some cell types, controlling intracellular zinc levels, affecting apoptotic and autophagy pathways. Some polymorphisms in this gene are associated with an increased risk of cancer. [provided by RefSeq, Sep 2017]

GeneCards Summary: MT2A (Metallothionein 2A) is a Protein Coding gene. Diseases associated with MT2A include Scrapie and Osteogenesis Imperfecta, Type X. Among its related pathways are Metal ion SLC transporters and Interferon gamma signaling. Gene Ontology (GO) annotations related to this gene include obsolete drug binding. An important paralog of this gene is MT1G.

UniProtKB/Swiss-Prot Summary: Metallothioneins have a high content of cysteine residues that bind various heavy metals; these proteins are transcriptionally regulated by both heavy metals and glucocorticoids.

8. Cellular Location of Gene Product

Predicted location: Intracellular [https://www.proteinatlas.org/ENSG00000125148/subcellular]

9. Mechanistic Information

Summary

MT2A, a gene encoding Metallothionein 2A, is intricately linked to the body's response to skeletal muscle toxicity or disease. When skeletal muscle faces injury or stress, such as contusion, oxidative stress, or hypoxia/reoxygenation, there's an elevation in reactive oxygen species (ROS) and metal ions like zinc and copper. MT2A expression is upregulated in these scenarios due to its metal-responsive elements (MREs) that bind to these elevated metal ions, activating gene expression [CS: 8]. The resultant Metallothionein 2A protein, rich in cysteine, binds these excess heavy metals, particularly zinc and copper [CS: 9]. This binding activity helps to mitigate the toxic effects of high metal ion concentration in cells, reducing cellular damage and aiding in recovery [CS: 8].

In response to skeletal muscle stress or disease, the expression of MT2A is involved in muscle cell growth and survival pathways [CS: 7]. Specifically, the absence or inhibition of MT2A, along with Metallothionein 1, has been shown to activate the Akt pathway [CS: 6]. This pathway is critical for cell survival and growth, and its activation leads to increased muscle fiber size, particularly in type IIb fibers, and enhances muscle strength [CS: 7]. In conditions of muscle stress or atrophy, such as in sarcopenia, MT2A's normal function appears to be a regulatory one, acting as a brake on the Akt pathway and thus on muscle growth [CS: 6]. Therefore, when MT2A is upregulated in response to muscle stress or injury, it may be contributing to a protective mechanism that prevents excessive muscle growth and maintains muscle homeostasis [CS: 6].

10. Upstream Regulators

11. Tissues/Cell Type Where Genes are Overexpressed

Tissue type enchanced: liver (tissue enhanced) [https://www.proteinatlas.org/ENSG00000125148/tissue]

Cell type enchanced: adipocytes, hepatocytes, monocytes, paneth cells, proximal enterocytes, proximal tubular cells (cell type enhanced) [https://www.proteinatlas.org/ENSG00000125148/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:

14. DisGeNet Biomarker Associations to Disease in Organ of Interest

Most relevant biomarkers with lower score or lower probability of association with disease or organ of interest: