MT2A: Metallothionein 2A – A Key Regulator of Metal Homeostasis and Cytoprotection
Comprehensive genomic and functional overview of the MT2A gene, its role in heavy metal detoxification, oxidative stress response, and association with human diseases.
Gene Information Card
| Symbol | MT2A |
|---|---|
| Full Name | Metallothionein 2A |
| Gene Type | protein-coding |
| Chromosomal Location | 16q13 |
| NCBI Gene ID | 4502 ncbi.nlm.nih.gov/gene/4502 |
| Ensembl ID | ENSG00000125148 |
| UniProt ID | P02795 |
| OMIM ID | 156360 |
| HGNC ID | 7406 |
| Aliases | MT2, MTC, MT-2, MT-II, MT2A |
Description
MT2A (metallothionein 2A) is a member of the metallothionein family of low-molecular-weight, cysteine-rich proteins. It binds essential and toxic heavy metals such as zinc, copper, and cadmium, playing a critical role in metal homeostasis, detoxification, and protection against oxidative stress. MT2A is inducible by various stimuli including metals, hormones, and inflammatory cytokines. Its expression is implicated in cell proliferation, apoptosis, and angiogenesis, and dysregulation is associated with several cancers, diabetes, and neurodegenerative diseases.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Cancer (various types) | Altered MT2A expression affects metal-dependent signaling and apoptosis; overexpression linked to chemoresistance | ClinVar, COSMIC, PubMed |
| Diabetes mellitus | MT2A modulates insulin secretion and protects pancreatic beta cells from oxidative damage | OMIM, PubMed |
| Alzheimer's disease | Dysregulated metal homeostasis and oxidative stress; MT2A levels altered in brain | NCBI Gene, PubMed |
| Atherosclerosis | MT2A protects against oxidative damage in vascular endothelial cells | PubMed |
| Cadmium toxicity | MT2A binds cadmium, reducing its toxic effects; polymorphisms may influence susceptibility | ClinVar, PubMed |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Liver | 120.5 | High |
| Kidney | 95.3 | High |
| Pancreas | 78.2 | High |
| Small intestine | 65.1 | Medium |
| Brain | 22.4 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HepG2 | 150.2 | Hepatocellular carcinoma cell line |
| HEK293 | 88.7 | Embryonic kidney cells |
| MCF7 | 45.3 | Breast cancer cell line |
| A549 | 60.1 | Lung carcinoma cell line |
| SH-SY5Y | 30.5 | Neuroblastoma cell line |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| rs28366003 | SNP (promoter) | 5-10% in certain populations | Alters MT2A expression; associated with cadmium accumulation and cancer risk |
| rs10636 | SNP (3' UTR) | Common (allele frequency ~30%) | May affect mRNA stability; linked to diabetes and metal toxicity |
| c.1A>G (p.Met1?) | Missense | Rare | Potential loss of start codon; functional impact unknown |
Mutation functional classification
Loss of Function (LOF)
Rare missense or promoter variants that reduce MT2A expression or metal-binding capacity, impairing detoxification and increasing oxidative stress.
Gain of Function (GOF)
Overexpression due to promoter polymorphisms or amplification; associated with chemoresistance in cancer.
Dominant Negative (DN)
Not well documented; MT2A functions as a monomer, dominant-negative effects are unlikely.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Metallothioneins bind metals (Reactome: R-HSA-5661231)
• Cellular response to zinc stress (Reactome: R-HSA-5661231)
• Metal ion homeostasis (KEGG: hsa04978)
• p53 signaling pathway (indirect via zinc regulation)
Protein Summary
Metallothionein-2A (MT2A) is a 61-amino-acid protein (6.2 kDa) containing 20 cysteine residues that coordinate up to 7 divalent metal ions (e.g., Zn²⁺, Cu²⁺, Cd²⁺) via thiolate bonds. It lacks aromatic amino acids and is highly conserved. MT2A functions as a cellular antioxidant, scavenging reactive oxygen species, and regulates zinc availability for transcription factors and enzymes. Its expression is rapidly induced by metals, glucocorticoids, and oxidative stress. Post-translational modifications include S-nitrosylation and phosphorylation, modulating its metal-binding and protective functions.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| KMT2A Knockout HEK293 Cell Line | EDJ-KQ50442 | Human | 4297 | Details Get a Quote |
| MT2A Knockout HEK293 Cell Line | EDJ-KQ50456 | Human | 4502 | Details Get a Quote |
| TRMT2A Knockout HEK293 Cell Line | EDJ-KQ51200 | Human | 27037 | Details Get a Quote |
| KMT2A Knockout HeLa Cell Line | EDJ-KQ53877 | Human | 4297 | Details Get a Quote |
| MT2A Knockout HeLa Cell Line | EDJ-KQ53914 | Human | 4502 | Details Get a Quote |
| TRMT2A Knockout HeLa Cell Line | EDJ-KQ55991 | Human | 27037 | Details Get a Quote |
| KMT2A Knockout A-549 Cell Line | EDJ-KQ62368 | Human | 4297 | Details Get a Quote |
| MT2A Knockout A-549 Cell Line | EDJ-KQ62407 | Human | 4502 | Details Get a Quote |
| TRMT2A Knockout A-549 Cell Line | EDJ-KQ64475 | Human | 27037 | Details Get a Quote |
| KMT2A Knockout HCT 116 Cell Line | EDJ-KQ70837 | Human | 4297 | Details Get a Quote |
| MT2A Knockout HCT 116 Cell Line | EDJ-KQ70874 | Human | 4502 | Details Get a Quote |
| TRMT2A Knockout HCT 116 Cell Line | EDJ-KQ72933 | Human | 27037 | Details Get a Quote |
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