Alternative titles; symbols
HGNC Approved Gene Symbol: TXNRD3
Cytogenetic location: 3q21.3 Genomic coordinates (GRCh38) : 3:126,607,050-126,655,124 (from NCBI)
Thioredoxin reductases (EC 1.6.4.5), such as TXNRD3, are selenocysteine (sec)-containing flavoenzymes that maintain thioredoxins, small proteins that catalyze redox reactions, in the reduced state using the reducing power of NADPH. The sec residue, which is essential for enzyme activity, is located in the penultimate C-terminal position and is encoded by a UGA codon. Sec differs from cys in that it substitutes selenium, a better nucleophile, for sulfur. Termination of polypeptide synthesis is prevented by a stem-loop structure called the selenocysteine insertion sequence, or SECIS, which is located in the 3-prime UTR (Gasdaska et al., 1999; Sun et al., 1999).
By searching an EST database with rat and human TXNRD1 (601112) as the probes, Sun et al. (1999) identified cDNAs encoding human and mouse TXNRD2 (606448) and TXNRD3, which they called TR3 and TR2, respectively. The predicted 579-amino acid TXNRD3 protein, which is 70% and 53% identical to TXNRD1 and TXNRD2, respectively, contains 2 N-terminal active-site redox cysteines, NADPH- and FAD-binding residues, a dimer interface domain, and a C-terminal sec residue. The 3-primer UTR of TXNRD3 has a SECIS element. Northern blot analysis revealed preferential expression of a 2.8-kb Txnrd3 transcript in mouse testis. Immunoblot analysis showed expression of a 65-kD Txnrd3 protein in mouse testis and liver.
By functional analysis, Sun et al. (1999) showed that the sec residue of TXNRD1 serves as a sensor of reactive oxygen species. Given the conservation of the sec residue in TXNRD2 and TXNRD3, they proposed that this ROS sensor function is conserved in these isozymes.
Gasdaska, P. Y., Berggren, M. M., Berry, M. J., Powis, G. Cloning, sequencing, and functional expression of a novel human thioredoxin reductase. FEBS Lett. 442: 105-111, 1999. [PubMed: 9923614] [Full Text: https://doi.org/10.1016/s0014-5793(98)01638-x]
Sun, Q.-A., Wu, Y., Zappacosta, F., Jeang, K.-T., Lee, B. J., Hatfield, D. L., Gladyshev, V. N. Redox regulation of cell signaling by selenocysteine in mammalian thioredoxin reductases. J. Biol. Chem. 274: 24522-24530, 1999. [PubMed: 10455115] [Full Text: https://doi.org/10.1074/jbc.274.35.24522]