thioredoxin reductase 1, cytoplasmic; TR; gene associated with retinoic & interferon-induced mortality 12 protein; GRIM-12; gene associated with retinoic & IFN-induced mortality 12 protein; KM-102-derived reductase-like factor; thioredoxin reductase TR1 (TXNRD1, GRIM12, KDRF)

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Function

thioredoxin + NADP(+) <--> thioredoxin disulfide + NADPH
active site is a redox-active disulfide bond
the selenocysteine residue is also essential for catalytic activity
isoform 1 may possess glutaredoxin activity as well as thioredoxin reductase activity & induces actin & tubulin polymerization, leading to formation of cell membrane protrusions
isoform 4 enhances the transcriptional activity of estrogen receptor alpha & estrogen receptor beta
isoform 5 enhances transcriptional activity of the beta receptor only
isoform 5 also mediates cell death induced by a combination of interferon-beta & retinoic acid
ISGylated (probable)
interacts with HERC5

Cofactor: binds 1 FAD per subunit

homodimer
he N-terminus of isoform 5 is blocked
the N-terminal glutaredoxin domain found in isoform 1 does not contain the C-P-Y-C redox-active motif normally found in glutaredoxins & has been found to be inactive in classical glutaredoxin assays
belongs to the class-I pyridine nucleotide-disulfide oxidoreductase family
contains 1 glutaredoxin domain
- contains redox-active disulfide bond
contains selenocysteine residue

isoform 1
- expressed predominantly in Leydig cells (at protein level)
- also expressed in ovary, spleen, heart, liver, kidney & pancreas & in a number of cancer cell lines
- induced by estradiol or testosterone in HeLa cells
isoform 4
- widely expressed
- highest levels in kidney, testis, uterus, ovary, prostate, placenta & fetal liver
isoform 5 is induced by a combination of interferon-beta & retinoic acid (at protein level)