Reduces disulfideprotein thioredoxin (Trx) to its dithiol-containing form (PubMed:8577704). Homodimeric flavoprotein involved in the regulation of cellular redox reactions, growth and differentiation. Contains a selenocysteine residue at the C-terminal active site that is essential for catalysis (Probable). Also has reductase activity on hydrogen peroxide (H2O2) (PubMed:10849437). Induces actin and tubulin polymerization, leading to formation of cell membrane protrusions. Enhances the transcriptional activity of estrogen receptors ESR1 and ESR2. Enhances the transcriptional activity of the estrogen receptor ESR2 only (PubMed:15199063). Mediates cell death induced by a combination of interferon-beta and retinoic acid (PubMed:9774665). [thioredoxin]-dithiol + NADP(+) = [thioredoxin]-disulfide + H(+) + NADPH H(+) + H2O2 + NADPH = 2 H2O + NADP(+) Binds 1 FAD per subunit. kcat is 100 min(-1) with H2O2 as substrate. Homodimer (PubMed:17512005, PubMed:8577704). Interacts with HERC5. Interacts with ESR1 and ESR2. Expressed predominantly in Leydig cells (at protein level). Also expressed in ovary, spleen, heart, liver, kidney and pancreas and in a number of cancer cell lines. Widely expressed with highest levels in kidney, testis, uterus, ovary, prostate, placenta and fetal liver. Induced by estradiol or testosterone in HeLa cells. Induced by a combination of interferon-beta and retinoic acid (at protein level). The N-terminal glutaredoxin domain does not contain the C-P-Y-C redox-active motif normally found in glutaredoxins and has been found to be inactive in classical glutaredoxin assays. The N-terminus is blocked. ISGylated. The thioredoxin reductase active site is a redox-active disulfide bond. The selenocysteine residue is also essential for catalytic activity. Minor isoform. Major isoform. The N-terminus of the sequence is processed into a mature form that lacks residues Met-151 and Asn-152 at the N-terminus. Belongs to the class-I pyridine nucleotide-disulfide oxidoreductase family. Truncated C-terminus. Truncated C-terminus. Truncated C-terminus. Truncated C-terminus. Truncated C-terminus. Truncated C-terminus. Truncated C-terminus. Truncated C-terminus. Truncated C-terminus. Truncated C-terminus. Truncated C-terminus. Truncated C-terminus. Truncated C-terminus.