Thioredoxin reductase 1, cytoplasmic
Short name=TR
EC=1.8.1.9
Alternative name(s):
Gene associated with retinoic and interferon-induced mortality 12 protein
Short name=GRIM-12
Short name=Gene associated with retinoic and IFN-induced mortality 12 protein
KM-102-derived reductase-like factor
Thioredoxin reductase TR1
- Function
- Isoform 1 may possess glutaredoxin activity as well as thioredoxin reductase activity and induces actin and tubulin polymerization, leading to formation of cell membrane protrusions. Isoform 4 enhances the transcriptional activity of estrogen receptors alpha and beta while isoform 5 enhances the transcriptional activity of the beta receptor only. Isoform 5 also mediates cell death induced by a combination of interferon-beta and retinoic acid.
- Catalytic activity
- Thioredoxin + NADP+ = thioredoxin disulfide + NADPH.
- Cofactor
- Binds 1 FAD per subunit.
- Subunit structure
- Homodimer. Isoform 4 interacts with ESR1 and ESR2. Interacts with HERC5.
- Subcellular location
- Cytoplasm / Isoform 4: Cytoplasm, Nucleus / Isoform 5: Cytoplasm
- Tissue specificity
- Isoform 1 is 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. Isoform 4 is widely expressed with highest levels in kidney, testis, uterus, ovary, prostate, placenta and fetal liver. Ref.2 Ref.17 Ref.20
- Induction
- Isoform 5 is induced by a combination of interferon-beta and retinoic acid (at protein level). Isoform 1 is induced by estradiol or testosterone in HeLa cells.
- Domain
- The N-terminal glutaredoxin domain found in isoform 1 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.
- Post-translational modification
- The N-terminus of isoform 5 is blocked. ISGylated
- Miscellaneous
- The thioredoxin reductase active site is a redox-active disulfide bond. The selenocysteine residue is also essential for catalytic activity.
Thioredoxin reductase 2, mitochondrial
EC=1.8.1.9
Alternative name(s):
Selenoprotein Z
Short name=SelZ
TR-beta
Thioredoxin reductase TR3
- Function
- Maintains thioredoxin in a reduced state. Implicated in the defenses against oxidative stress. May play a role in redox-regulated cell signaling.
- Catalytic activity
- Thioredoxin + NADP+ = thioredoxin disulfide + NADPH.
- Cofactor
- FAD By similarity.
- Subunit structure
- Homodimer. UniProtKB P38816
- Subcellular location
- Mitochondrion Ref.2 Ref.3.
- Tissue specificity
- Highly expressed in the prostate, ovary, liver, testis, uterus, colon and small intestine. Intermediate levels in brain, skeletal muscle, heart and spleen. Low levels in placenta, pancreas, thymus and peripheral blood leukocytes. According to Ref.5, high levels in kidney, whereas according to Ref.2, levels are low. Ref.2 Ref.3 Ref.5
- Miscellaneous
- The active site is a redox-active disulfide bond. The selenocysteine residue is essential for enzymatic activity
Thioredoxin
Short name=Trx
Alternative name(s):
ATL-derived factor
Short name=ADF
Surface-associated sulphydryl protein
Short name=SASP
- Sequence length
- 105 AA.
- Function
- Participates in various redox reactions through the reversible oxidation of its active center dithiol to a disulfide and catalyzes dithiol-disulfide exchange reactions. Plays a role in the reversible S-nitrosylation of cysteine residues in target proteins, and thereby contributes to the response to intracellular nitric oxide. Nitrosylates the active site Cys of CASP3 in response to nitric oxide (NO), and thereby inhibits caspase-3 activity. Induces the FOS/JUN AP-1 DNA-binding activity in ionizing radiation (IR) cells through its oxidation/reduction status and stimulates AP-1 transcriptional activity. Ref.17 Ref.19 Ref.20 Ref.22 Ref.23
ADF augments the expression of the interleukin-2 receptor TAC (IL2R/P55). Ref.17 Ref.19 Ref.20 Ref.22 Ref.23
- Subunit structure
- Homodimer; disulfide-linked. Interacts with TXNIP through the redox-active site. Interacts with MAP3K5 and CASP3. In case of infection, interacts with S.typhimurium protein slrP. Interacts with APEX1; the interaction stimulates the FOS/JUN AP-1 DNA-binding activity in a redox-dependent manner.
- Subcellular location
- Nucleus. Cytoplasm. Secreted. Note: Secreted by a leaderless secretory pathway. Predominantly in the cytoplasm in non irradiated cells. Radiation induces translocation of TRX from the cytoplasm to the nucleus.
- Induction
- Up-regulated by ionizing radiation.
- Post-translational modification
- In the fully reduced protein, both Cys-69 and Cys-73 are nitrosylated in response to nitric oxide (NO). When two disulfide bonds are present in the protein, only Cys-73 is nitrosylated. Cys-73 can serve as donor for nitrosylation of target proteins.
In case of infection, ubiquitinated by S.typhimurium protein slrP, leading to its degradation.
