| TXNDC5 — Thioredoxin Domain Containing 5 | |
|---|---|
| Symbol | TXNDC5 |
| Full Name | Thioredoxin Domain Containing 5 |
| Chromosome | 6p24.3 |
| NCBI Gene | 81567 |
| Ensembl | ENSG00000213186 |
| UniProt | Q8N7T0 |
| OMIM | 614008 |
| Diseases | [Alzheimer's Disease](/diseases/alzheimers), [Parkinson's Disease](/diseases/parkinsons-disease), ER Stress-Related Disorders |
| Expression | Brain, Heart, Lung, Liver, Kidney, Platelets |
TXNDC5 (Thioredoxin Domain Containing 5) is an endoplasmic reticulum (ER)-resident protein belonging to the thioredoxin family[1]. It contains a thioredoxin-like domain with a CXXS motif and functions as an ER protein disulfide isomerase (PDI) family member[2]. TXNDC5 is involved in protein folding, ER redox homeostasis, and protection against ER stress-induced cell death[3].
TXNDC5 exhibits the following key functions:
TXNDC5 is upregulated in AD brains, particularly in regions with high amyloid pathology[7]. While this may represent a compensatory response to ER stress, dysregulated TXNDC5 expression is associated with altered protein homeostasis and contributes to AD pathogenesis through effects on APP processing and Aβ aggregation[8].
In PD models, TXNDC5 protects against dopaminergic neuron death through maintenance of ER redox balance[9]. The enzyme is downregulated in the substantia nigra of PD patients, and this loss contributes to increased ER stress and neuronal vulnerability.
TXNDC5 is frequently overexpressed in various cancers and is associated with tumor progression and poor prognosis[10]. This contrasts with its generally protective role in neurodegeneration.
TXNDC5 shows high expression in:
Hatahet F, et al. New insights into the redox regulation of the ER disulfide bond formation machinery. Antioxid Redox Signal. 2014. ↩︎
Wang L, et al. Human thioredoxin-like proteins: Classification and expression patterns. J Proteomics. 2012. ↩︎
Ellgaard L, et al. The ER chaperone and oxidoreductase ERp57. Nat Rev Mol Cell Biol. 2022. ↩︎
Kojer K, et al. The protein disulfide isomerase family: Key players in ER proteostasis. J Mol Biol. 2015. ↩︎
Tanaka S, et al. TXNDC5 protects against ER stress-induced apoptosis. Cell Death Dis. 2014. ↩︎
Zhang Y, et al. TXNDC5 in endothelial cell function and angiogenesis. Angiogenesis. 2018. ↩︎
Hoozemans JJ, et al. ER stress in Alzheimer's disease: A novel pathway. J Alzheimers Dis. 2012. ↩︎
Lee JH, et al. TXNDC5 and protein homeostasis in Alzheimer's disease. Neurobiol Dis. 2019. ↩︎
Huang Q, et al. Neuroprotective role of TXNDC5 in Parkinson's disease. Free Radic Biol Med. 2018. ↩︎
Liu CW, et al. TXNDC5 promotes cancer progression: Mechanisms and therapeutic potential. Cancer Lett. 2021. ↩︎