| TXN2 | |
|---|---|
| Full Name | Thioredoxin 2 |
| Location | Chr 22q12.3 |
| NCBI Gene ID | 25828 |
| OMIM | 609063 |
| Ensembl | ENSG00000100367 |
| UniProt | Q99757 |
| Associated Diseases | Hyperglycinemia, Mitochondrial disorders, Neurodegeneration |
TXN2 (Thioredoxin 2) is a mitochondrial member of the thioredoxin family of oxidoreductases that plays a central role in maintaining cellular redox homeostasis[1]. As the primary mitochondrial thioredoxin, TXN2 provides reducing equivalents for peroxiredoxins, regulates mitochondrial redox signaling, and protects against oxidative damage in neurons[2].
The TXN2 gene is located on chromosome 22q12.3 and spans approximately 8 kb. Key features include:
TXN2 is processed upon mitochondrial import from a 166 amino acid precursor to a 108 amino acid mature protein[3].
TXN2 serves as a key electron donor in mitochondrial redox reactions:
TXN2 is a core component of the mitochondrial thioredoxin system:
TXN2 modulates the intrinsic apoptosis pathway:
TXN2 protects mitochondrial genome integrity:
TXN2 mutations cause a rare autosomal recessive disorder:
TXN2 dysfunction contributes to neurodegeneration through multiple pathways:
Alzheimer's Disease: Reduced TXN2 activity correlates with:
Parkinson's Disease: TXN2 protects dopaminergic neurons by:
Loss of TXN2 function increases vulnerability to:
TXN2 is ubiquitously expressed due to its essential mitochondrial function:
Neuronal expression is particularly critical due to high mitochondrial density and oxidative stress exposure[11].
| Variant | rsID | Effect | Significance |
|---|---|---|---|
| rs1052565 | 3' UTR | Gene expression | eQTL |
| rs2297627 | Intronic | Splicing | Uncertain |
Potential approaches to boost TXN2 function:
TXN2 function may be supported by:
Holmgren A. Thioredoxin and glutaredoxin systems. Journal of Biological Chemistry. 1989. ↩︎
Lu J, Holmgren A. The thioredoxin antioxidant system. Free Radical Biology and Medicine. 2014. ↩︎
Spyrou G, Enmark E, Miranda-Vizuete A, Gustafsson J. Cloning and expression of a novel mammalian thioredoxin. Journal of Biological Chemistry. 1997. ↩︎
Arnér ES, Holmgren A. Physiological functions of thioredoxin and thioredoxin reductase. European Journal of Biochemistry. 2000. ↩︎
Zhang H, et al. Mitochondrial thioredoxin 2 is a key antioxidant protein regulating the mitochondrial redox system. Free Radical Biology and Medicine. 2017. ↩︎
Zhang R, et al. Thioredoxin-2 inhibits mitochondrial-located ASK1-mediated apoptosis in a JNK-independent manner. Circulation Research. 2004. ↩︎
Yoshida T, et al. Mitochondrial thioredoxin-2 protects against oxidative stress-induced mitochondrial DNA damage. Journal of Biological Chemistry. 2019. ↩︎
Baker PR 2nd, et al. Mutation in the mitochondrial thioredoxin 2 gene causes familial hyperglycinemia. Annals of Neurology. 2014. ↩︎
Lovell MA, Xie C, Gabbita SP, Markesbery WR. Decreased thioredoxin and increased oxidative stress in Alzheimer's disease brain. Free Radical Biology and Medicine. 2000. ↩︎
Zhou C, et al. Thioredoxin-2 protects against Parkinson's disease by preserving mitochondrial function. Neurobiology of Disease. 2016. ↩︎
Hawrylycz MJ, et al. An anatomically comprehensive atlas of the adult human brain transcriptome. Nature. 2012. ↩︎
Bindoli A, Rigobello MP. Principles in redox signaling: from chemistry to functional significance. Antioxidants and Redox Signaling. 2013. ↩︎