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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)
Function:
1) thioredoxin + NADP(+) thioredoxin disulfide + NADPH
2) active site is a redox-active disulfide bond
3) the selenocysteine residue is also essential for catalytic activity
4) isoform 1 may possess glutaredoxin activity as well as thioredoxin reductase activity & induces actin & tubulin polymerization, leading to formation of cell membrane protrusions
5) isoform 4 enhances the transcriptional activity of estrogen receptor alpha & estrogen receptor beta
6) isoform 5 enhances transcriptional activity of the beta receptor only
7) isoform 5 also mediates cell death induced by a combination of interferon-beta & retinoic acid
8) ISGylated (probable)
9) interacts with HERC5
Cofactor: binds 1 FAD per subunit
Structure:
- 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
Compartment:
- cytoplasm (putative)
- isoform 4: cytoplasm, nucleus
Alternative splicing: named isoforms=6
Expression:
- 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)
General
oxidoreductase
phosphoprotein
Properties
SIZE: entity length = 649 aa
MW = 71 kD
COMPARTMENT: cytoplasm
cell nucleus
MOTIF: Glutaredoxin {56-156}
Tyr phosphorylation site {Y161}
Tyr phosphorylation site {Y163}
cofactor-binding site [192-209]
COFACTOR-BOUND: flavin adenine dinucleotide
MOTIF: cysteine residue {C209}
MODIFICATION: cysteine residue {C214}
cysteine residue {C214}
MODIFICATION: cysteine residue {C209}
Tyr phosphorylation site {Y281}
Tyr phosphorylation site {Y572}
histidine residue {H622}
selenocysteine residue {C648}
Database Correlations
OMIM 601112
UniProt Q16881
PFAM correlations
Entrez Gene 7296
KEGG correlations
ENZYME 1.8.1.9
References
- UniProt :accession Q16881
- NIEHS-SNPs
http://egp.gs.washington.edu/data/txnrd1/