TXNRD1

TXNRD1, or thioredoxin reductase 1 (TR1), is a cytosolic selenoprotein that forms part of the thioredoxin system and catalyzes the NADPH-dependent reduction of oxidized thioredoxin. It is a flavoprotein enzyme that typically functions as a homodimer and contains an FAD-binding domain and a C-terminal selenocysteine residue, the latter encoded by a UGA codon and dependent on selenium for incorporation. Through its redox-active center, TXNRD1 transfers electrons from NADPH via FAD to thioredoxin, which in turn reduces a variety of disulfide bonds in cellular substrates.

By regenerating reduced thioredoxin, TXNRD1 indirectly supports the activity of many Thiol-Disulfide exchange enzymes, including ribonucleotide reductase, thereby contributing to DNA synthesis and repair, antioxidant defense, and redox signaling. The enzyme helps maintain cellular redox homeostasis and protects against oxidative stress. TXNRD1 is predominantly cytosolic, but nuclear localization has been observed under certain conditions, and its expression is broadly distributed across tissues. Its transcription and translation are influenced by cellular redox state and selenium availability, reflecting its status as a selenoprotein.

Clinical and research relevance include its upregulation in various cancers, where it may promote cell proliferation and contribute to chemoresistance, making TXNRD1 a potential therapeutic target. Inhibitors of thioredoxin reductases, such as auranofin, are studied for cancer and parasitic diseases, highlighting TXNRD1’s potential as a drug target. Related components of the system include thioredoxin (TXN) and NADPH.