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Information on EC 1.8.1.9 - thioredoxin-disulfide reductase and Organism(s) Homo sapiens and UniProt Accession Q86VQ6

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IUBMB Comments
A flavoprotein (FAD).
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Select one or more organisms in this record: ?
This record set is specific for:
Homo sapiens
UNIPROT: Q86VQ6
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Word Map
The taxonomic range for the selected organisms is: Homo sapiens
The enzyme appears in selected viruses and cellular organisms
Synonyms
thioredoxin reductase, trxr, trxr1, txnrd1, thioredoxin reductase 1, trxr2, txnrd2, thioredoxin reductase-1, thioredoxin reductase 2, nadph-dependent thioredoxin reductase, more
SYNONYM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
thioredoxin reductase
-
general stress protein 35
-
-
-
-
GSP35
-
-
-
-
hemolysate thioredoxin reductase
-
-
hemolysate TR
-
-
NADP-linked thioredoxin reductase
-
-
NADP-thioredoxin reductase
-
-
-
-
NADPH-dependent thioredoxin reductase-1
-
-
NADPH-thioredoxin reductase
-
-
-
-
NADPH2:oxidized thioredoxin oxidoreductase
-
-
-
-
reductase, thioredoxin
-
-
-
-
thioredoxin reductase
thioredoxin reductase (NADPH)
-
-
-
-
thioredoxin reductase 1
thioredoxin reductase-1
TR2
-
isoform
TR3
testes-specific isoform
TRR2
-
-
TrxR1
TrxR2
Txnrd1
TXNRD1-v3
-
splice variant
Txnrd2
TXNRD3
-
isozyme
REACTION
REACTION DIAGRAM
COMMENTARY hide
ORGANISM
UNIPROT
LITERATURE
thioredoxin + NADP+ = thioredoxin disulfide + NADPH + H+
show the reaction diagram
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
redox reaction
-
-
-
-
oxidation
-
-
-
-
reduction
-
-
-
-
PATHWAY SOURCE
PATHWAYS
-
-
SYSTEMATIC NAME
IUBMB Comments
thioredoxin:NADP+ oxidoreductase
A flavoprotein (FAD).
CAS REGISTRY NUMBER
COMMENTARY hide
9074-14-0
-
SUBSTRATE
PRODUCT                       
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
thioredoxin disulfide + NADPH + H+
thioredoxin + NADP+
show the reaction diagram
2 ferricytochrome c + NADH
2 ferrocytochrome c + NAD+ + H+
show the reaction diagram
-
-
-
?
5,5'-dithiobis(2-nitrobenzoic acid) + NADPH
2-nitro-5-thiobenzoate + NADP+
show the reaction diagram
5,5'-dithiobis(2-nitrobenzoic acid) + NADPH + H+
2-nitro-5-thiobenzoate + NADP+
show the reaction diagram
5,5'-dithiobis(2-nitrobenzoic acid) + NADPH + H+
5'-thionitrobenzoic acid + NADP+
show the reaction diagram
5,5'-dithiobis(2-nitrobenzoic acid) + NADPH + H+
thionitrobenzoic acid + NADP+
show the reaction diagram
-
-
-
-
?
5,5'-dithiobis-(2-nitrobenzoic acid) + NADPH + H+
2-nitro-5-thiobenzoate + NADP+
show the reaction diagram
-
-
-
-
?
chaetocin + NADPH + H+
?
show the reaction diagram
-
competitive and selective substrate for TrxR1
-
-
?
chetomin + NADPH + H+
?
show the reaction diagram
-
-
-
-
?
cytochrome c + NADPH
reduced cytochrome c + NADP+
show the reaction diagram
-
-
-
?
dithiothreitol + NADPH
?
show the reaction diagram
-
-
-
-
?
gliotoxin + NADPH + H+
?
show the reaction diagram
-
-
-
-
?
GSSG + NADPH
GSH + NADP+
show the reaction diagram
insulin + NADPH + H+
? + NADP+
show the reaction diagram
-
-
-
-
?
juglone + NADPH + H+
?
show the reaction diagram
lipoamide + NADPH + H+
?
show the reaction diagram
-
isoform TrxR2 displays strikingly lower activity with lipoamide compared to isoform TrxR1
-
-
?
lipoic acid + NADPH + H+
?
show the reaction diagram
-
substrate for isoform TrxR1
-
-
?
menadione + NADPH
?
show the reaction diagram
-
-
-
-
?
methylseleninate + H2O2
?
show the reaction diagram
-
in presence of methylseleninate
-
-
?
methylseleninate + NADPH
CH3SeH + NADP+
show the reaction diagram
-
also utilizes glutathione instead of NADPH
-
ir
NADH + ubiquinone-10
NAD+ + ubiquinol-10
show the reaction diagram
-
-
-
-
?
NADPH + H+ + ubiquinone-10
NADP+ + ubiquinol-10
show the reaction diagram
oxidized lipoate + NADPH
?
show the reaction diagram
-
-
-
-
?
rat thioredoxin + NADP+
rat thioredoxin disulfide + NADPH + H+
show the reaction diagram
-
-
-
-
r
reduced tissue factor + NADP+
tissue factor + NADPH + H+
show the reaction diagram
-
-
-
r
seleninate + NADPH
?
show the reaction diagram
-
-
-
-
?
thioredoxin + NADP+
thioredoxin disulfide + NADPH
show the reaction diagram
thioredoxin + NADP+
thioredoxin disulfide + NADPH + H+
show the reaction diagram
thioredoxin + tert-butyl-hydroperoxide
?
show the reaction diagram
-
in presence of methylseleninate, coupled assay
-
-
?
thioredoxin 1 + NADP+
thioredoxin 1 disulfide + NADPH + H+
show the reaction diagram
-
TrxR2 prefers its endogenous substrate thioredocin 2 over thioredoxin 1 (10fold), whereas isoform TrxR1 efficiently reduces both thioredoxin 1 and thioredoxin 2
-
-
?
thioredoxin 2 + NADP+
thioredoxin 2 disulfide + NADPH + H+
show the reaction diagram
-
TrxR2 prefers its endogenous substrate thioredocin 2 over thioredoxin 1 (10fold), whereas isoform TrxR1 efficiently reduces both thioredoxin 1 and thioredoxin 2
-
-
?
thioredoxin disulfide + NADPH + H+
?
show the reaction diagram
-
-
-
-
?
thioredoxin disulfide + NADPH + H+
thioredoxin + NADP+
show the reaction diagram
tissue factor + NADPH + H+
reduced tissue factor + NADP+
show the reaction diagram
-
-
-
r
additional information
?
-
NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
thioredoxin disulfide + NADPH + H+
thioredoxin + NADP+
show the reaction diagram
the enzyme (TrxR) can use NADPH to reduce thioredoxin disulfide which passes the reducing equivalent to its downstream substrates involved in various biomedical events, such as ribonucleotide reductase for deoxyribonucleotide and DNA synthesis, or peroxiredoxins for counteracting oxidative stress
-
-
?
NADPH + H+ + ubiquinone-10
NADP+ + ubiquinol-10
show the reaction diagram
-
HEK cells overexpressing TrxR1 reduce ubiquinone-10
-
-
?
thioredoxin + NADP+
thioredoxin disulfide + NADPH
show the reaction diagram
thioredoxin 1 + NADP+
thioredoxin 1 disulfide + NADPH + H+
show the reaction diagram
-
TrxR2 prefers its endogenous substrate thioredocin 2 over thioredoxin 1 (10fold), whereas isoform TrxR1 efficiently reduces both thioredoxin 1 and thioredoxin 2
-
-
?
thioredoxin 2 + NADP+
thioredoxin 2 disulfide + NADPH + H+
show the reaction diagram
-
TrxR2 prefers its endogenous substrate thioredocin 2 over thioredoxin 1 (10fold), whereas isoform TrxR1 efficiently reduces both thioredoxin 1 and thioredoxin 2
-
-
?
thioredoxin disulfide + NADPH + H+
thioredoxin + NADP+
show the reaction diagram
additional information
?
-
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
selenium
contains a selenocysteine in its active site
Selenite
selenium treatment results in increased expression of almost all TrxR1 mRNA variants with increasing concentrations of selenite
selenium
selenocysteine
additional information
-
selenoprotein
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
(1E,4Z,6E)-1,7-di-2-furyl-5-hydroxyhepta-1,4,6-trien-3-one
-
-
(1E,4Z,6E)-1-(2-bromophenyl)-5-hydroxy-7-(4-hydroxyphenyl)hepta-1,4,6-trien-3-one
-
-
(1E,4Z,6E)-1-[4-(dimethylamino)phenyl]-5-hydroxy-7-[5-(hydroxymethyl)-2-furyl]hepta-1,4,6-trien-3-one
-
-
(1E,4Z,6E)-5-hydroxy-1,7-bis(4-hydroxy-3-methoxyphenyl)hepta-1,4,6-trien-3-one
-
-
(1E,4Z,6E)-5-hydroxy-1,7-bis(5-methyl-2-furyl)hepta-1,4,6-trien-3-one
-
-
(1E,4Z,6E)-5-hydroxy-1-(4-hydroxy-3-methoxyphenyl)-7-(5-methyl-2-furyl)hepta-1,4,6-trien-3-one
-
-
(1E,4Z,6E)-5-hydroxy-1-(4-hydroxy-3-methoxyphenyl)-7-[5-(hydroxymethyl)-2-furyl]hepta-1,4,6-trien-3-one
-
-
(1E,4Z,6E)-5-hydroxy-1-(4-hydroxyphenyl)-7-(2-thienyl)hepta-1,4,6-trien-3-one
-
-
(1E,4Z,6E)-5-hydroxy-7-(4-hydroxy-3-methoxyphenyl)-1-(4-hydroxyphenyl)hepta-1,4,6-trien-3-one
-
-
(1E,4Z,6E)-5-hydroxy-7-(4-hydroxy-3-methoxyphenyl)-1-phenylhepta-1,4,6-trien-3-one
-
-
(1E,4Z,6E)-5-hydroxy-7-(4-hydroxyphenyl)-1-(3,4,5-trimethoxyphenyl)hepta-1,4,6-trien-3-one
-
-
(1E,4Z,6E)-5-hydroxy-7-(4-hydroxyphenyl)-1-phenylhepta-1,4,6-trien-3-one
-
-
(1E,4Z,6E)-5-hydroxy-7-[5-(hydroxymethyl)-2-furyl]-1-(3,4,5-trimethoxyphenyl)hepta-1,4,6-trien-3-one
-
-
(1E,4Z,6E)-5-hydroxy-7-[5-(hydroxymethyl)-2-furyl]-1-(4-methoxyphenyl)hepta-1,4,6-trien-3-one
-
-
(1E,4Z,6E)-5-hydroxy-7-[5-(hydroxymethyl)-2-furyl]-1-phenylhepta-1,4,6-trien-3-one
-
-
(2E,6E)-2-(4-hydroxybenzylidene)-6-(4-hydroxy-3-methoxybenzylidene)cyclohexanone
-
-
(2E,6E)-2-[(4-hydroxyphenyl)methylidene]-6-[(3,4,5-trimethoxyphenyl)methylidene]cyclohexanone
-
-
(4-ammoniothiophenolato)(2,2':6',2''-terpyridine)platinum(II) chloride
-
-
(4-ammoniothiophenolato)(4'-toyl-2,2':6',2''-terpyridine)platinum(II) nitrate
-
-
(4-hydroxylthiophenolato)(2,2':6',2''-terpyridine)platinum(II) chloride
-
-
(4-hydroxylthiophenolato)(4'-toyl-2,2':6',2''-terpyridine)platinum(II) chloride
-
-
(4-methylpyrimidine-2-thiolato-kappaS)(1,3,5-triaza-7-phosphatricyclo[3.3.1.13,7]decane-kappaP)gold
-
-
(4-methylpyrimidine-2-thiolato-kappaS)[1,1'-(1,3,7-triaza-5-phosphabicyclo[3.3.1]nonane-3,7-diyl-kappaP)diethanone]gold
-
-
(N-acetyl-4-aminothiophenolato)(2,2':6',2''-terpyridine)platinum(II) chloride
-
-
(N-acetyl-4-aminothiophenolato)(4'-toyl-2,2':6',2''-terpyridine)platinum(II) nitrate
-
-
(pyridine-2-thiolato-kappaS)(1,3,5-triaza-7-phosphatricyclo[3.3.1.13,7]decane-kappaP)gold
-
-
(pyridine-2-thiolato-kappaS)[1,1'-(1,3,7-triaza-5-phosphabicyclo[3.3.1]nonane-3,7-diyl-kappaP)diethanone]gold
-
-
(pyrimidine-2-thiolato-kappaS)(1,3,5-triaza-7-phosphatricyclo[3.3.1.13,7]decane-kappaP)gold
-
-
1,1'-sulfanediylbis(2,4-dinitrobenzene)
-
IC50: 0.004 mM
1,1'-sulfanediylbis[2-nitro-4-(trifluoromethyl)benzene]
-
IC50: 0.15 mM
1,2-[bis(1,2-benzisoselenazolone-3(2H)-ketone)]ethane
-
apoptosis induced by the inhibitor is through Bcl-2/Bax and caspase-3 pathways
1,3-dinitro-5-(trifluoromethyl)benzene
-
IC50: 0.2 mM
1-chloro-2,4-dinitrobenzene
1-Fluoro-2,4-dinitrobenzene
-
irreversible, with NADPH, alkylation of the active site cysteine disulfide, strong increase in oxidation activity of the enzyme against NADPH
1-methyl-1-propyl-2-imidazolyl disulfide
-
13-cis-retinoic acid
-
-
2-benzoyloxycinnamaldehyde
-
-
2-benzyloxycinnamaldehyde
-
-
2-chloro-1,3-dinitro-5-(trifluoromethyl)benzene
-
IC50: 0.1 mM
2-hydroxycinnamaldehyde
-
-
2-hydroxymethyl-5-methoxy-1-methyl-3-[(2,4,6-trifluorophenoxy)methyl]indole-4,7-dione
-
maximum inhibition is achieved 5 min after addition of 0.003 mM
2-hydroxymethyl-5-methoxy-1-methyl-3-[(4-nitrophenoxy)methyl]indole-4,7-dione
-
-
2-hydroxymethyl-6-methoxy-1-methyl-3-[(4-nitrophenoxy)methyl]indole-4,7-dione
-
-
2-pentoxycinnamaldehyde
-
-
3-Bromopropionate
-
-
4,5-dinitro-1,3-benzodioxole
-
IC50: 0.08 mM
4,6-dinitro-2,1,3-benzothiadiazole
-
IC50: 0.002 mM
4-nitro-2,1,3-benzothiadiazole
-
IC50: 0.05 mM
4-Vinylpyridine
-
irreversible
5,5'-dithiobis(2-nitrobenzoate)
-
above 0.1 mM
5-fluoro-2-hydroxycinnamaldehyde
-
-
5-methoxy-1,2-dimethyl-3-[1-oxo-2-(2,4,6-trifluorophenyl)ethyl]indole-4,7-dione
-
-
5-methoxy-1-methyl-3-[(2,4,6-trifluorophenoxy)methyl]indole-4,7-dione
-
-
5-methoxy-1-methyl-3-[(4-nitrophenoxy)methyl]indole-4,7-dione
-
-
5-nitro-1,3-benzodioxole
-
IC50: 0.2 mM
5-nitro-2,1,3-benzothiadiazole
-
IC50: 0.09 mM
6,7-dinitroquinoxaline
-
IC50: 0.14 mM
6-methoxy-1-methyl-3-[(2,4,6-trifluorophenoxy)methyl]indole-4,7-dione
-
-
6-methoxy-1-methyl-3-[(4-nitrophenoxy)methyl]indole-4,7-dione
-
-
6-nitroquinoxaline
-
IC50: 0.2 mM
allyl isothiocyanate
-
0.0205 mM, 50% inhibition after 30 min preincubation in assay with 5,5'-dithiobis(2-nitrobenzoic acid) as substrate
arsenic trioxide
-
irreversible. Both the N-terminal redox-active dithiol and the C-terminal selenothiol-active site of reduced TrxR may participate in the reaction with the inhibitor. The inhibition of MCF-7 cell growth by arsenic trioxide is correlated with irreversible inactivation of thioredoxin reductase, which subsequently led to thioredoxin oxidation
arsenite
-
-
auranofin
aurothioglucose
Benzyl isothiocyanate
-
0.0033 mM, 50% inhibition after 30 min preincubation in assay with 5,5'-dithiobis(2-nitrobenzoic acid) as substrate
calveolin
overexpression of caveolin 1 inhibits TrxR activity by about 50% whereas a lack of caveolin 1 activates TrxR, both in vitro and in vivo
-
chaetocin
-
competitive inhibitor with anticancer effects, complete inhibition at 0.015 mM
cisplatin
Cr6+
-
hexavalent chromium causes pronounced inhibition of TrxR, the inhibition of TrxR is not reversed by removal of residual Cr6+ or by NADPH. In cells treated with 0.025 or 0.050 mM Cr6+ for 90 min, TrxR activity is inhibited by 71 and 77%, respectively, while after 180 min of the same treatments, TrxR is inhibited by 97 and 85%, respectively
diallyl disulfide
-
0.38 mM, 50% inhibition after 30 min preincubation in assay with 5,5'-dithiobis(2-nitrobenzoic acid) as substrate
ES936
-
i.e. 5-methoxy-1,2-dimethyl-3-[(4-nitrophenoxy)methyl]indole-4,7-dione, potent inhibitor
gold
-
potent inhibitor, the inhibition of TrxR1 by the metal compound is not markedly influenced by the presence of EDTA
iodoacetate
K2PdCl4
-
strong and irreversible inhibition, about 30% residual activity at 400 nM in the presence of NADPH, less than 10% residual activity at 400 nM for 5,5'-dithiobis(2-nitrobenzoic acid) reduction, about 90% residual activity at 400 nM for juglone reduction
K2PdCl6
-
irreversible inhibition
K2PtCl4
-
irreversible inhibition, about 5% residual activity at 400 nM in the presence of NADPH, complete inhibition of 5,5'-dithiobis(2-nitrobenzoic acid) reduction at 400 nM, about 90% residual activity at 400 nM for juglone reduction
K2PtCl6
-
irreversible inhibition
KAuCl4
-
irreversible inhibition, about 10% residual activity at 400 nM in the presence of NADPH, less than 5% residual activity at 400 nM for 5,5'-dithiobis(2-nitrobenzoic acid) reduction, about 70% residual activity at 400 nM for juglone reduction
menadione
-
methylmercury
-
in the case of methylmercury, a ratio of 16 molecules per dimer leads to a virtually inactive enzyme
oxaliplatin
-
palladium
-
potent inhibitor, the inhibition of TrxR1 by the metal compound is not markedly influenced by the presence of EDTA
palmarumycin CP1
-
0.001 mM, the naphthoquinone spiroketal fungal metabolite palmarumycin CP1 is a potent inhibitor of thioredoxin reductase-1, IC50: 0.00035 mM
palmitoyl-CoA
covalent inhibition of TrxR1/hTrx1 by palmitoyl-CoA. The palmitoyl-CoA/TrxR1 reaction is NADPH-dependent and produces palmitoylated TrxR1 at an active site selenocysteine residue
phenethyl isothiocyanate
-
0.075 mM, 50% inhibition after 30 min preincubation in assay with 5,5'-dithiobis(2-nitrobenzoic acid) as substrate
platinum
-
the inhibition of TrxR1 by the metal compound is not markedly influenced by the presence of EDTA
PX-911
-
0.001 mM, a water-soluble prodrug of a palmarumycin CP1 analogue, IC50: 0.0032 mM
PX-916
-
0.001 mM, a water-soluble prodrug of a palmarumycin CP1 analogue, potent inhibitor of purified human thioredoxin reductase-1, IC50: 0.00028 mM
PX-960
-
0.001 mM, a water-soluble prodrug of a palmarumycin CP1 analogue, IC50: 0.00027 mM
sulforaphane
-
0.04 mM, 50% inhibition after 30 min preincubation in assay with 5,5'-dithiobis(2-nitrobenzoic acid) as substrate
trans,trans-curcumin
trans-cinnamaldehyde
-
-
trisodium (4,5-dihydro-1,3-thiazole-2-thiolato-kappaS2)[3,3',3''-(phosphanetriyl-kappaP)tribenzenesulfonato(3-)]aurate(3-)
-
-
trisodium [3,3',3''-(phosphanetriyl-kappaP)tribenzenesulfonato(3-)](pyrimidine-2-thiolato-kappaS)aurate(3-)
-
-
Zn2+
-
0.1-0.2 mM and above
[(iPr2Im)2Au]Cl
-
mainly inhibits isoform TrxR2, about 30% residual activity after 8 h at 0.005 mM or 0.05 mM
[Au(d2pype)2]Cl
-
mainly inhibits isoform TrxR1, about 30% residual activity after 8 h at 0.005 mM, about 10% residual activity after 8 h at 0.05 mM
[Au(d2pypp)2]Cl
-
about 30% residual activity after 8 h at 0.005 mM, about 10% residual activity after 8 h at 0.05 mM
additional information
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
cysteine
EDTA
-
if the concentration of EDTA in the reaction mixture is higher than 0.1 mM the enzyme shows full activity
phosphate
-
under growth conditions
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.088 - 4.5
5,5'-dithiobis(2-nitrobenzoic acid)
0.0046
chaetocin
-
in 100 mM potassium phosphate (pH 7.0), at 22°C
0.0161
chetomin
-
in 100 mM potassium phosphate (pH 7.0), at 22°C
0.116
DTNB
-
-
0.0169
gliotoxin
-
in 100 mM potassium phosphate (pH 7.0), at 22°C
0.0019 - 0.0043
Lipoamide
0.0027
lipoic acid
-
isoform TrxR1, in 50 mM Tris-HCl, 1 mM EDTA, pH 8.0, at 37°C
0.018
methylseleninate
-
-
0.088 - 4.5
NADPH
0.00141 - 0.1047
thioredoxin
additional information
additional information
-
-
-
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.012 - 33.33
5,5'-dithiobis(2-nitrobenzoic acid)
29.5
DTNB
-
-
1.6 - 3.3
Lipoamide
1.8
lipoic acid
-
isoform TrxR1, in 50 mM Tris-HCl, 1 mM EDTA, pH 8.0, at 37°C
23
methylseleninate
-
-
1.83
rat thioredoxin
-
insulin coupled assay
-
0.016 - 46.57
thioredoxin
kcat/KM VALUE [1/mMs-1]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
21.2 - 333.5
5,5'-dithiobis(2-nitrobenzoic acid)
372 - 1737
Lipoamide
667
lipoic acid
-
isoform TrxR1, in 50 mM Tris-HCl, 1 mM EDTA, pH 8.0, at 37°C
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
additional information
additional information
kinetics of theaflavins exhibit a mixed type of competitive and non-competitive inhibition, with Kis 4 mg/ml and Kii 26 mg/ml against coenzyme NADPH, and with Kis 12 mg/ml and Kii 27 mg/ml against substrate 5,5'-dithiobis(2-nitrobenzoic acid)
-
IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.0383
(1E,4Z,6E)-1,7-di-2-furyl-5-hydroxyhepta-1,4,6-trien-3-one
Homo sapiens
-
pH 7.4, 37°C
0.05
(1E,4Z,6E)-1-(2-bromophenyl)-5-hydroxy-7-(4-hydroxyphenyl)hepta-1,4,6-trien-3-one
Homo sapiens
-
pH 7.4, 37°C
0.0622
(1E,4Z,6E)-1-[4-(dimethylamino)phenyl]-5-hydroxy-7-[5-(hydroxymethyl)-2-furyl]hepta-1,4,6-trien-3-one
Homo sapiens
-
pH 7.4, 37°C
0.0003
(1E,4Z,6E)-5-hydroxy-1,7-bis(4-hydroxy-3-methoxyphenyl)hepta-1,4,6-trien-3-one
Homo sapiens
-
pH 7.4, 37°C
0.0016
(1E,4Z,6E)-5-hydroxy-1,7-bis(5-methyl-2-furyl)hepta-1,4,6-trien-3-one
Homo sapiens
-
pH 7.4, 37°C
0.0005
(1E,4Z,6E)-5-hydroxy-1-(4-hydroxy-3-methoxyphenyl)-7-(5-methyl-2-furyl)hepta-1,4,6-trien-3-one
Homo sapiens
-
pH 7.4, 37°C
0.001
(1E,4Z,6E)-5-hydroxy-1-(4-hydroxy-3-methoxyphenyl)-7-[5-(hydroxymethyl)-2-furyl]hepta-1,4,6-trien-3-one
Homo sapiens
-
pH 7.4, 37°C
0.02
(1E,4Z,6E)-5-hydroxy-1-(4-hydroxyphenyl)-7-(2-thienyl)hepta-1,4,6-trien-3-one
Homo sapiens
-
pH 7.4, 37°C
0.02
(1E,4Z,6E)-5-hydroxy-7-(4-hydroxy-3-methoxyphenyl)-1-(4-hydroxyphenyl)hepta-1,4,6-trien-3-one
Homo sapiens
-
pH 7.4, 37°C
0.057
(1E,4Z,6E)-5-hydroxy-7-(4-hydroxy-3-methoxyphenyl)-1-phenylhepta-1,4,6-trien-3-one
Homo sapiens
-
pH 7.4, 37°C
0.0138
(1E,4Z,6E)-5-hydroxy-7-(4-hydroxyphenyl)-1-(3,4,5-trimethoxyphenyl)hepta-1,4,6-trien-3-one
Homo sapiens
-
pH 7.4, 37°C
0.0233
(1E,4Z,6E)-5-hydroxy-7-(4-hydroxyphenyl)-1-phenylhepta-1,4,6-trien-3-one
Homo sapiens
-
pH 7.4, 37°C
0.002
(1E,4Z,6E)-5-hydroxy-7-[5-(hydroxymethyl)-2-furyl]-1-(3,4,5-trimethoxyphenyl)hepta-1,4,6-trien-3-one
Homo sapiens
-
pH 7.4, 37°C
0.0008
(1E,4Z,6E)-5-hydroxy-7-[5-(hydroxymethyl)-2-furyl]-1-(4-methoxyphenyl)hepta-1,4,6-trien-3-one
Homo sapiens
-
pH 7.4, 37°C
0.0013
(1E,4Z,6E)-5-hydroxy-7-[5-(hydroxymethyl)-2-furyl]-1-phenylhepta-1,4,6-trien-3-one
Homo sapiens
-
pH 7.4, 37°C
0.0051
(2E,6E)-2-(4-hydroxybenzylidene)-6-(4-hydroxy-3-methoxybenzylidene)cyclohexanone
Homo sapiens
-
pH 7.4, 37°C
0.0249
(2E,6E)-2-[(4-hydroxyphenyl)methylidene]-6-[(3,4,5-trimethoxyphenyl)methylidene]cyclohexanone
Homo sapiens
-
pH 7.4, 37°C
0.00007442
(4-ammoniothiophenolato)(2,2':6',2''-terpyridine)platinum(II) chloride
Homo sapiens
in 50 mM Tris-HCl, pH 8.0, at 37°C
-
0.00007002
(4-ammoniothiophenolato)(4'-toyl-2,2':6',2''-terpyridine)platinum(II) nitrate
Homo sapiens
in 50 mM Tris-HCl, pH 8.0, at 37°C
-
0.00006977
(4-hydroxylthiophenolato)(2,2':6',2''-terpyridine)platinum(II) chloride
Homo sapiens
in 50 mM Tris-HCl, pH 8.0, at 37°C
-
0.00005826
(4-hydroxylthiophenolato)(4'-toyl-2,2':6',2''-terpyridine)platinum(II) chloride
Homo sapiens
in 50 mM Tris-HCl, pH 8.0, at 37°C
-
0.00000096 - 0.00000406
(4-methylpyrimidine-2-thiolato-kappaS)(1,3,5-triaza-7-phosphatricyclo[3.3.1.13,7]decane-kappaP)gold
0.00000155 - 0.00000586
(4-methylpyrimidine-2-thiolato-kappaS)[1,1'-(1,3,7-triaza-5-phosphabicyclo[3.3.1]nonane-3,7-diyl-kappaP)diethanone]gold
0.00007426
(N-acetyl-4-aminothiophenolato)(2,2':6',2''-terpyridine)platinum(II) chloride
Homo sapiens
in 50 mM Tris-HCl, pH 8.0, at 37°C
-
0.00007786
(N-acetyl-4-aminothiophenolato)(4'-toyl-2,2':6',2''-terpyridine)platinum(II) nitrate
Homo sapiens
in 50 mM Tris-HCl, pH 8.0, at 37°C
-
0.00000161 - 0.00000412
(pyridine-2-thiolato-kappaS)(1,3,5-triaza-7-phosphatricyclo[3.3.1.13,7]decane-kappaP)gold
0.00000154 - 0.0000062
(pyridine-2-thiolato-kappaS)[1,1'-(1,3,7-triaza-5-phosphabicyclo[3.3.1]nonane-3,7-diyl-kappaP)diethanone]gold
0.00000192 - 0.00000673
(pyrimidine-2-thiolato-kappaS)(1,3,5-triaza-7-phosphatricyclo[3.3.1.13,7]decane-kappaP)gold
0.004
1,1'-sulfanediylbis(2,4-dinitrobenzene)
Homo sapiens
-
IC50: 0.004 mM
0.15
1,1'-sulfanediylbis[2-nitro-4-(trifluoromethyl)benzene]
Homo sapiens
-
IC50: 0.15 mM
0.2
1,3-dinitro-5-(trifluoromethyl)benzene
Homo sapiens
-
IC50: 0.2 mM
0.1
2-chloro-1,3-dinitro-5-(trifluoromethyl)benzene
Homo sapiens
-
IC50: 0.1 mM
0.08
4,5-dinitro-1,3-benzodioxole
Homo sapiens
-
IC50: 0.08 mM
0.002
4,6-dinitro-2,1,3-benzothiadiazole
Homo sapiens
-
IC50: 0.002 mM
0.05
4-nitro-2,1,3-benzothiadiazole
Homo sapiens
-
IC50: 0.05 mM
0.2
5-nitro-1,3-benzodioxole
Homo sapiens
-
IC50: 0.2 mM
0.09
5-nitro-2,1,3-benzothiadiazole
Homo sapiens
-
IC50: 0.09 mM
0.14
6,7-dinitroquinoxaline
Homo sapiens
-
IC50: 0.14 mM
0.2
6-nitroquinoxaline
Homo sapiens
-
IC50: 0.2 mM
0.0205
allyl isothiocyanate
Homo sapiens
-
25°C, 30 min preincubation in assay with 5,5'-dithiobis(2-nitrobenzoic acid) as substrate
0.00000074 - 0.00000245
auranofin
0.0033
Benzyl isothiocyanate
Homo sapiens
-
25°C, 30 min preincubation in assay with 5,5'-dithiobis(2-nitrobenzoic acid) as substrate
0.004
chaetocin
Homo sapiens
-
using 5,5'-dithiobis(2-nitrobenzoic acid) as substrate, in 100 mM potassium phosphate (pH 7.0), at 22°C
0.38
diallyl disulfide
Homo sapiens
-
25°C, 30 min preincubation in assay with 5,5'-dithiobis(2-nitrobenzoic acid) as substrate
0.00035
palmarumycin CP1
Homo sapiens
-
0.001 mM, the naphthoquinone spiroketal fungal metabolite palmarumycin CP1 is a potent inhibitor of thioredoxin reductase-1, IC50: 0.00035 mM
0.075
phenethyl isothiocyanate
Homo sapiens
-
25°C, 30 min preincubation in assay with 5,5'-dithiobis(2-nitrobenzoic acid) as substrate
0.0032
PX-911
Homo sapiens
-
0.001 mM, a water-soluble prodrug of a palmarumycin CP1 analogue, IC50: 0.0032 mM
0.00028
PX-916
Homo sapiens
-
0.001 mM, a water-soluble prodrug of a palmarumycin CP1 analogue, potent inhibitor of purified human thioredoxin reductase-1, IC50: 0.00028 mM
0.00027
PX-960
Homo sapiens
-
0.001 mM, a water-soluble prodrug of a palmarumycin CP1 analogue, IC50: 0.00027 mM
0.04
sulforaphane
Homo sapiens
-
25°C, 30 min preincubation in assay with 5,5'-dithiobis(2-nitrobenzoic acid) as substrate
0.0015 - 0.01
trans,trans-curcumin
0.00000167 - 0.00000682
trisodium (4,5-dihydro-1,3-thiazole-2-thiolato-kappaS2)[3,3',3''-(phosphanetriyl-kappaP)tribenzenesulfonato(3-)]aurate(3-)
0.00000062 - 0.00000695
trisodium [3,3',3''-(phosphanetriyl-kappaP)tribenzenesulfonato(3-)](pyrimidine-2-thiolato-kappaS)aurate(3-)
additional information
additional information
Homo sapiens
black tea extract and theaflavins (mixture of theaflavin, theaflavin-3-monogallate, theaflavin-3'-monogallate and theaflavin-3,3'-digallate) inhibit the purified TrxR1 with IC50 44 mg/ml and 21 mg/ml, respectively
-
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
0.003
-
TrxR-16 mutant K29R/H108Y/A119N/V478E
0.007
-
TrxR-16 mutant K29R/H108Y
0.016
-
TrxR-16 mutant K29R
0.025
-
TrxR-16, TrxR lacking the last 16 C-terminal amino acids
0.035
-
mutant U498C
31
-
DTNB coupled assay, purified enzyme
33.8
-
purified enzyme
42
-
purified enzyme, coupled assay with DTNB
additional information
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
7
-
assay at
8
-
assay at
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
20
-
assay at
25
-
assay at
40
-
reduction of insulin
52
-
reduction of DTNB
ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
-
Uniprot
Manually annotated by BRENDA team
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
SOURCE
human kidney renal cell carcinoma
Manually annotated by BRENDA team
-
-
Manually annotated by BRENDA team
-
genetic polymorphisms in the human selenoprotein P gene is associated with differences in thioredoxin reductase 1 concentrations
Manually annotated by BRENDA team
-
-
Manually annotated by BRENDA team
TXNRD1_v3 is induced by estradiol or testosterone treatments
Manually annotated by BRENDA team
transcription of TXNRD1 involves alternative splicing, leading to a number of transcripts also encoding isoforms of TrxR1 that differ from each other at their N-terminal domains. The TXNRD1_v3 isoform contains an atypical N-terminal glutaredoxin domain. Expression of the transcript of this isoform is found predominantly in testis but is also detected in ovary, spleen, heart, liver, kidney, and pancreas
Manually annotated by BRENDA team
TXNRD1_v3 is predominantly expressed in the Leydig cells
Manually annotated by BRENDA team
quantification of the expression of alternative mRNA forms (alpha1/2, alpha6, alpha7/8, alpha10/11, alpha13, gamma2-4, and beta1) in six different human malignant mesothelioma cell lines of epithelioid (STAV-AB and M-14-K), sarcomatoid (STAV-FCS and ZL34), or mixed phenotype (M-28-K and M-9-K). The lowest level of TrxR1 is seen for the two sarcomatoid forms (STAV-FCS and ZL34), whereas the epithelioid phenotypes generally show very high levels of TrxR1. The major transcript form expressed in all cell lines is alpha1/2, followed by alpha7/8. The lowest level is observed for alpha6, which comprises less than 1% of the total a forms
Manually annotated by BRENDA team
TXNRD1_v3 is induced by estradiol or testosterone treatments
Manually annotated by BRENDA team
H157, U1810 and H611. Selenium treatment results in increased expression of almost all TrxR1 mRNA variants with increasing concentrations of selenite
Manually annotated by BRENDA team
in some case of glucocorticoid-resistant alopecia areata patients, the expression of TrxR1 is decreased in outer root sheath
Manually annotated by BRENDA team
-
inhibition of thioredoxin reductase by auranofin induces apoptosis in cisplatin-resistant human ovarian cancer cells
Manually annotated by BRENDA team
transcription of TXNRD1 involves alternative splicing, leading to a number of transcripts also encoding isoforms of TrxR1 that differ from each other at their N-terminal domains. The TXNRD1_v3 isoform contains an atypical N-terminal glutaredoxin domain. Expression of the transcript of this isoform is found predominantly in testis but is also detected in ovary, spleen, heart, liver, kidney, and pancreas
Manually annotated by BRENDA team
-
-
Manually annotated by BRENDA team
U1906E and U1906L. Selenium treatment results in increased expression of almost all TrxR1 mRNA variants with increasing concentrations of selenite
Manually annotated by BRENDA team
human cell glioblastoma
Manually annotated by BRENDA team
transcription of TXNRD1 involves alternative splicing, leading to a number of transcripts also encoding isoforms of TrxR1 that differ from each other at their N-terminal domains. The TXNRD1_v3 isoform contains an atypical N-terminal glutaredoxin domain. Expression of the transcript of this isoform is found predominantly in testis but is also detected in ovary, spleen, heart, liver, kidney, and pancreas
Manually annotated by BRENDA team
thioredoxin reductase 1 is upregulated in synovial cell from patients with rheumatoid arthritis. TRXR1 suppresses hydrogen peroxide and inhibits apoptosis of rheumatoid arthritis synovial cells
Manually annotated by BRENDA team
-
thioredoxin reductase activity in rheumatoid arthritis cells is significantly higher than in osteoarthritis cells
Manually annotated by BRENDA team
Hg(II) potently inhibits (at concentrations of 5-50 nM) TrxR1 activity in both cell-free and intracellular assays
Manually annotated by BRENDA team
TXNRD1_v3 is induced by estradiol or testosterone treatments
Manually annotated by BRENDA team
additional information
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY hide
GeneOntology No.
LITERATURE
SOURCE
-
TrxR1
Manually annotated by BRENDA team
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
drug target
anti-cancer target. Selenocysteine is important for the biological functions of mammalian TrxR and distinguishes it from prokaryotic thioredoxin reductases. Therefore it is a promising drug target
physiological function
the enzyme (TrxR) can use NADPH to reduce thioredoxin disulfide which passes the reducing equivalent to its downstream substrates involved in various biomedical events, such as ribonucleotide reductase for deoxyribonucleotide and DNA synthesis, or peroxiredoxins for counteracting oxidative stress
drug target
anti-cancer target. Selenocysteine is important for the biological functions of mammalian TrxR and distinguishes it from prokaryotic thioredoxin reductases. Therefore it is a promising drug target
malfunction
-
stable knockdown of TxnRd1 in both HeLa and FaDu cells nearly abolishes curcumin-mediated radiosensitization. TxnRd1 knockdown cells show decreased radiation-induced reactive oxygen species and sustained extracellular signal-regulated kinase 1/2 activation
metabolism
-
the TrxR/thioredoxin pathway is of central importance in limiting cellular reactive oxygen species
physiological function
UNIPROT
ENTRY NAME
ORGANISM
NO. OF AA
NO. OF TRANSM. HELICES
MOLECULAR WEIGHT[Da]
SOURCE
SEQUENCE
LOCALIZATION PREDICTION?
TRXR3_HUMAN
643
0
70683
Swiss-Prot
other Location (Reliability: 3)
PDB
SCOP
CATH
UNIPROT
ORGANISM
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
105000
-
gel filtration
110000
120000
-
-
130000 - 160000
-
sucrose density gradient centrifugation and gel filtration
53117
-
2 * 53117, isoform TrxR1, calculated from amino acid sequence
54769
-
2 * 54769, isoform TrxR2, calculated from amino acid sequence
54800
-
2 * 54800, HeLa cell enzyme, MALDI
55000
57000
-
2 * 57000, SDS-PAGE
58000
60000
-
2 * 60000, SDS-PAGE
65000
-
SDS-PAGE
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
dimer
homodimer
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
side-chain modification
enhanced TrxR1/thioredoxin palmitoylation occurs in parallel with a decrease in their activities. Palmitoylated TrxR1/thioredoxin is mainly generated by autoacylation
additional information
-
no glycosyl groups on the protein
CRYSTALLIZATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
crystals of hTrxR1 are grown at 25°C by the hanging-drop technique. Crystal structure of hTrxR1 (Sec->Cys) in complex with FAD and NADP+ at a resolution of 2.8 A
in complex with FAD, NADPH and/or (N-acetyl-4-aminothiophenolato)(2,2':6',2''-terpyridine)platinum(II) chloride, sitting drop vapor diffusion method, using 5 mM MgSO4, 5% (w/v) PEG 3350, 50 mM MES pH 6.0 and 20% (w/v) 1,6-hexanediol
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
C73S
-
recombinant, His-tagged
TrxR-16
-
truncated form of TrxR missing the last 16 C-terminal amino acids, without thioredoxin-reducing activity
TrxR-16 K29R
-
without thioredoxin-reducing activity
TrxR-16 K29R/H108Y
-
without thioredoxin-reducing activity
TrxR-16 K29R/H108Y/A119N/V478E
-
without thioredoxin-reducing activity
U498C
-
1.4fold higher GSSG-reducing activity compared to the TrxR-16 enzyme
TEMPERATURE STABILITY
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
60
-
1 h, no loss of activity
65
-
above, irreversible loss of activity, no displacement of tightly bound FAD
GENERAL STABILITY
ORGANISM
UNIPROT
LITERATURE
tightly bound FAD is not replaced during heat treatment or guanidinium hydrochloride
-
OXIDATION STABILITY
ORGANISM
UNIPROT
LITERATURE
the reduced enzyme is very labile to O2, decrease of selenium content and activity after exposure to air, protection by NADPH, NADP+ and tris-(2-carboxyethyl)phosphine
-
394954
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
2',5'-ADP Sepharose column chromatography, PAO Sepharose column chromatography, and Superdex 200 gel filtration
-
HeLa cells, partially
-
heparin affinity depends on the selenium content, binding can be induced by reduction of the enzyme with NADPH or tris-(2-carboxyethyl)phosphine
-
HisBind HiTrap metal-affinity column chromatography, 2',5'-ADP-Sepharose column chromatography, and CNBr-activated Sepharose column chromatography
-
Ni-NTA resin affinity chromatography
-
Ni-Sepharose column chromatography
Ni2+ affinity column chromatography
Sepharose affinity column chromatography
-
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
expressed in Escherichia coli
expressed in Escherichia coli BL21(DE3) cells
expressed in Escherichia coli BL21(DE3) or ER2566 cells
-
HEK-293 cells overexpressing TrxR2 are more resistant to impairment of complex III bypassing function of TrxR2
EXPRESSION
ORGANISM
UNIPROT
LITERATURE
TxnRd1 expression is elevated by more than 50fold in FaDu and HeLa cells and by more than 20fold in SCC-1 cells compared with either MSK-Leuk1 cells or keratinocytes. TxnRd activity is about 20fold higher in FaDu and HeLa cells and about 7fold higher in SCC-1 cells compared with that in keratinocytes or MSK-Leuk1 cells
-
APPLICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
medicine
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Schallreuter, K.U.; Wood, J.M.
Calcium regulates thioredoxin reductase in human metastatic melanoma
Biochim. Biophys. Acta
997
242-247
1989
Homo sapiens
Manually annotated by BRENDA team
Schallreuter, K.U.; Pittelkow, M.R.; Wood, J.M.
EF-Hands calcium binding regulates the thioredoxin reductase/thioredoxin electron transfer in human keratinocytes
Biochem. Biophys. Res. Commun.
162
1311-1316
1989
Escherichia coli, Homo sapiens
Manually annotated by BRENDA team
Schallreuter, K.U.; Wood, J.M.
The stereospecific suicide inhibition of human melanoma thioredoxin reductase by 13-cis-retinoic acid
Biochem. Biophys. Res. Commun.
160
573-579
1989
Homo sapiens
Manually annotated by BRENDA team
Schallreuter, K.U.; Wood, J.M.
The activity and purification of membrane-associated thioredoxin reductase from human metastatic melanotic melanoma
Biochim. Biophys. Acta
967
103-109
1988
Homo sapiens
Manually annotated by BRENDA team
Schallreuter, K.U.; Wood, J.M.
The role of thioredoxin reductase in the reduction of free radicals at the surface of the epidermis
Biochem. Biophys. Res. Commun.
136
630-637
1986
Cavia porcellus, Homo sapiens
Manually annotated by BRENDA team
Lik-Shing Tsang, M.; Weatherbee, J.A.
Thioredoxin, glutaredoxin, and thioredoxin reductase from cultured HeLa cells
Proc. Natl. Acad. Sci. USA
78
7478-7482
1981
Homo sapiens
Manually annotated by BRENDA team
Oblong, J.E.; Gasdaska, P.Y.; Sherrill, K.; Powis, G.
Purification of human thioredoxin reductase: properties and characterization by absorption and circular dichroism spectroscopy
Biochemistry
32
7271-7277
1993
Homo sapiens
Manually annotated by BRENDA team
Liu, S.Y.; Stadtman, T.
Heparin-binding properties of selenium-containing thioredoxin reductase from HeLa cells and human lung adenocarcinoma cells
Proc. Natl. Acad. Sci. USA
94
6138-6141
1997
Homo sapiens
Manually annotated by BRENDA team
Tamura, T.; Stadtman, T.C.
A new selenoprotein from human lung adenocarcinoma cells: purification, properties, and thioredoxin reductase activity
Proc. Natl. Acad. Sci. USA
93
1006-1011
1996
Homo sapiens
Manually annotated by BRENDA team
Arner, E.S.J.; Bjoernstedt, M.; Holmgren, A.
1-Chloro-2,4-dinitrobenzene is an irreversible inhibitor of human thioredoxin reductase. Loss of thioredoxin disulfide reductase activity is accompanied by a large increase in NADPH oxidase activity
J. Biol. Chem.
270
3479-3482
1995
Homo sapiens
Manually annotated by BRENDA team
Nordberg, J.; Zhong, L.; Holmgren, A.; Arner, E.S.J.
Mammalian thioredoxin reductase is irreversibly inhibited by dinitrohalobenzenes by alkylation of both the redox active selenocysteine and its neighboring cysteine residue
J. Biol. Chem.
273
10835-10842
1998
Bos taurus, Homo sapiens
Manually annotated by BRENDA team
Sun, Q.A.; Zappacosta, F.; Factor, V.M.; Wirth, P.J.; Hatfield, D.L.; Gladyshev, V.N.
Heterogeneity within animal thioredoxin reductases. Evidence for alternative first exon splicing
J. Biol. Chem.
276
3106-3114
2001
Drosophila melanogaster, Drosophila melanogaster (P91938), Homo sapiens, Homo sapiens (Q9NNW7), Mus musculus, Mus musculus (Q9JMH6), Rattus norvegicus
Manually annotated by BRENDA team
Gromer, S.; Gross, J.H.
Methylseleninate is a substrate rather than an inhibitor of mammalian thioredoxin reductase: implications for the antitumor effects of selenium
J. Biol. Chem.
277
9701-9706
2002
Drosophila melanogaster, Homo sapiens, Mus musculus, Plasmodium falciparum
Manually annotated by BRENDA team
Gorlatov, S.N.; Stadtman, T.C.
Human selenium-dependent thioredoxin reductase from HeLa cells: properties of forms with differing heparin affinities
Arch. Biochem. Biophys.
369
133-142
1999
Homo sapiens
Manually annotated by BRENDA team
Nalvarte, I.; Damdimopoulos, A.E.; Spyrou, G.
Human mitochondrial thioredoxin reductase reduces cytochrome c and confers resistance to complex III inhibition
Free Radic. Biol. Med.
36
1270-1278
2004
Homo sapiens (Q16881), Homo sapiens (Q9NNW7), Homo sapiens
Manually annotated by BRENDA team
Rundlof, A.K.; Janard, M.; Miranda-Vizuete, A.; Arner, E.S.J.
Evidence for intriguingly complex transcription of human thioredoxin reductase 1
Free Radic. Biol. Med.
36
641-656
2004
Homo sapiens
Manually annotated by BRENDA team
Xia, L.; Nordman, T.; Olsson, J.M.; Damdimopoulos, A.; Bjorkhem-Bergman, L.; Nalvarte, I.; Eriksson, L.C.; Arner, E.S.; Spyrou, G.; Bjornstedt, M.
The mammalian cytosolic selenoenzyme thioredoxin reductase reduces ubiquinone. A novel mechanism for defense against oxidative stress
J. Biol. Chem.
278
2141-2146
2003
Bos taurus, Escherichia coli, Homo sapiens, Rattus norvegicus
Manually annotated by BRENDA team
Andricopulo, A.D.; Akoachere, M.B.; Krogh, R.; Nickel, C.; McLeish, M.J.; Kenyon, G.L.; Arscott, L.D.; Williams, C.H.; Davioud-Charvet, E.; Becker, K.
Specific inhibitors of Plasmodium falciparum thioredoxin reductase as potential antimalarial agents
Bioorg. Med. Chem. Lett.
16
2283-2292
2006
Homo sapiens, Plasmodium falciparum
Manually annotated by BRENDA team
Urig, S.; Lieske, J.; Fritz-Wolf, K.; Irmler, A.; Becker, K.
Truncated mutants of human thioredoxin reductase 1 do not exhibit glutathione reductase activity
FEBS Lett.
580
3595-3600
2006
Homo sapiens
Manually annotated by BRENDA team
Fang, J.; Lu, J.; Holmgren, A.
Thioredoxin reductase is irreversibly modified by curcumin: a novel molecular mechanism for its anticancer activity
J. Biol. Chem.
280
25284-25290
2005
Homo sapiens, Rattus norvegicus
Manually annotated by BRENDA team
Turanov, A.A.; Su, D.; Gladyshev, V.N.
Characterization of alternative cytosolic forms and cellular targets of mouse mitochondrial thioredoxin reductase
J. Biol. Chem.
281
22953-22963
2006
Homo sapiens, Mus musculus
Manually annotated by BRENDA team
Karunasinghe, N.; Ferguson, L.R.; Tuckey, J.; Masters, J.
Hemolysate thioredoxin reductase and glutathione peroxidase activities correlate with serum selenium in a group of New Zealand men at high prostate cancer risk
J. Nutr.
136
2232-2235
2006
Homo sapiens
Manually annotated by BRENDA team
Matsuzaka, Y.; Okamoto, K.; Mabuchi, T.; Iizuka, M.; Ozawa, A.; Oka, A.; Tamiya, G.; Kulski, J.K.; Inoko, H.
Identification and characterization of novel variants of the thioredoxin reductase 3 new transcript 1 TXNRD3NT1
Mamm. Genome
16
41-49
2005
Homo sapiens (Q86VQ6), Homo sapiens
Manually annotated by BRENDA team
Powis, G.; Wipf, P.; Lynch, S.M.; Birmingham, A.; Kirkpatrick, D.L.
Molecular pharmacology and antitumor activity of palmarumycin-based inhibitors of thioredoxin reductase
Mol. Cancer Ther.
5
630-636
2006
Homo sapiens
Manually annotated by BRENDA team
Sohn, K.C.; Jang, S.; Choi, D.K.; Lee, Y.S.; Yoon, T.J.; Jeon, E.K.; Kim, K.H.; Seo, Y.J.; Lee, J.H.; Park, J.K.; Kim, C.D.
Effect of thioredoxin reductase 1 on glucocorticoid receptor activity in human outer root sheath cells
Biochem. Biophys. Res. Commun.
356
810-815
2007
Homo sapiens (Q16881), Homo sapiens
Manually annotated by BRENDA team
Kabuyama, Y.; Kitamura, T.; Yamaki, J.; Homma, M.K.; Kikuchi, S.; Homma, Y.
Involvement of thioredoxin reductase 1 in the regulation of redox balance and viability of rheumatoid synovial cells
Biochem. Biophys. Res. Commun.
367
491-496
2008
Homo sapiens (Q16881), Homo sapiens
Manually annotated by BRENDA team
Watson, W.H.; Heilman, J.M.; Hughes, L.L.; Spielberger, J.C.
Thioredoxin reductase-1 knock down does not result in thioredoxin-1 oxidation
Biochem. Biophys. Res. Commun.
368
832-836
2008
Homo sapiens (Q16881)
Manually annotated by BRENDA team
Selenius, M.; Fernandes, A.P.; Brodin, O.; Bjoernstedt, M.; Rundloef, A.K.
Treatment of lung cancer cells with cytotoxic levels of sodium selenite: effects on the thioredoxin system
Biochem. Pharmacol.
75
2092-2099
2008
Homo sapiens (Q16881), Homo sapiens
Manually annotated by BRENDA team
Sroka, J.; Antosik, A.; Czyz, J.; Nalvarte, I.; Olsson, J.M.; Spyrou, G.; Madeja, Z.
Overexpression of thioredoxin reductase 1 inhibits migration of HEK-293 cells
Biol. Cell
99
677-687
2007
Homo sapiens (Q16881)
Manually annotated by BRENDA team
Hu, Y.; Urig, S.; Koncarevic, S.; Wu, X.; Fischer, M.; Rahlfs, S.; Mersch-Sundermann, V.; Becker, K.
Glutathione- and thioredoxin-related enzymes are modulated by sulfur-containing chemopreventive agents
Biol. Chem.
388
1069-1081
2007
Homo sapiens
Manually annotated by BRENDA team
Qiu, X.; Liu, Z.; Shao, W.Y.; Liu, X.; Jing, D.P.; Yu, Y.J.; An, L.K.; Huang, S.L.; Bu, X.Z.; Huang, Z.S.; Gu, L.Q.
Synthesis and evaluation of curcumin analogues as potential thioredoxin reductase inhibitors
Bioorg. Med. Chem.
16
8035-8041
2008
Homo sapiens
Manually annotated by BRENDA team
Yan, H.; Harding, J.J.; Xing, K.; Lou, M.F.
Revival of glutathione reductase in human cataractous and clear lens extracts by thioredoxin and thioredoxin reductase, in conjunction with alpha-crystallin or thioltransferase
Curr. Eye Res.
32
455-463
2007
Homo sapiens
Manually annotated by BRENDA team
Rundloef, A.; Fernandes, A.P.; Selenius, M.; Babic, M.; Shariatgorji, M.; Nilsonne, G.; Ilag, L.L.; Dobra, K.; Bjoernstedt, M.
Quantification of alternative mRNA species and identification of thioredoxin reductase 1 isoforms in human tumor cells
Differentiation
75
123-132
2007
Homo sapiens (Q16881), Homo sapiens
Manually annotated by BRENDA team
Meplan, C.; Crosley, L.K.; Nicol, F.; Beckett, G.J.; Howie, A.F.; Hill, K.E.; Horgan, G.; Mathers, J.C.; Arthur, J.R.; Hesketh, J.E.
Genetic polymorphisms in the human selenoprotein P gene determine the response of selenoprotein markers to selenium supplementation in a gender-specific manner (the SELGEN study)
FASEB J.
21
3063-3074
2007
Homo sapiens
Manually annotated by BRENDA team
Marzano, C.; Gandin, V.; Folda, A.; Scutari, G.; Bindoli, A.; Rigobello, M.P.
Inhibition of thioredoxin reductase by auranofin induces apoptosis in cisplatin-resistant human ovarian cancer cells
Free Radic. Biol. Med.
42
872-881
2007
Homo sapiens
Manually annotated by BRENDA team
Lemarechal, H.; Anract, P.; Beaudeux, J.L.; Bonnefont-Rousselot, D.; Ekindjian, O.G.; Borderie, D.
Impairment of thioredoxin reductase activity by oxidative stress in human rheumatoid synoviocytes
Free Radic. Res.
41
688-698
2007
Homo sapiens
Manually annotated by BRENDA team
Cunnea, P.; Fernandes, A.P.; Capitanio, A.; Eken, S.; Spyrou, G.; Bjoernstedt, M.
Increased expression of specific thioredoxin family proteins; a pilot immunohistochemical study on human hepatocellular carcinoma
Int. J. Immunopathol. Pharmacol.
20
17-24
2007
Homo sapiens (Q16881), Homo sapiens
Manually annotated by BRENDA team
Bacon, J.R.; Plumb, G.W.; Howie, A.F.; Beckett, G.J.; Wang, W.; Bao, Y.
Dual action of sulforaphane in the regulation of thioredoxin reductase and thioredoxin in human HepG2 and Caco-2 cells
J. Agric. Food Chem.
55
1170-1176
2007
Homo sapiens
Manually annotated by BRENDA team
Dammeyer, P.; Damdimopoulos, A.E.; Nordman, T.; Jimenez, A.; Miranda-Vizuete, A.; Arner, E.S.
Induction of cell membrane protrusions by the N-terminal glutaredoxin domain of a rare splice variant of human thioredoxin reductase 1
J. Biol. Chem.
283
2814-2821
2008
Homo sapiens (Q16881), Homo sapiens
Manually annotated by BRENDA team
Fritz-Wolf, K.; Urig, S.; Becker, K.
The structure of human thioredoxin reductase 1 provides insights into C-terminal rearrangements during catalysis
J. Mol. Biol.
370
116-127
2007
Homo sapiens (Q16881), Homo sapiens
Manually annotated by BRENDA team
Cao, Z.; Bhella, D.; Lindsay, J.G.
Reconstitution of the mitochondrial PrxIII antioxidant defence pathway: general properties and factors affecting PrxIII activity and oligomeric state
J. Mol. Biol.
372
1022-1033
2007
Homo sapiens
Manually annotated by BRENDA team
Peng, Z.F.; Lan, L.X.; Zhao, F.; Li, J.; Tan, Q.; Yin, H.W.; Zeng, H.H.
A novel thioredoxin reductase inhibitor inhibits cell growth and induces apoptosis in HL-60 and K562 cells
J. Zhejiang Univ. Sci. B
9
16-21
2008
Homo sapiens
Manually annotated by BRENDA team
Huber, K.; Patel, P.; Zhang, L.; Evans, H.; Westwell, A.D.; Fischer, P.M.; Chan, S.; Martin, S.
2-[(1-methylpropyl)dithio]-1H-imidazole inhibits tubulin polymerization through cysteine oxidation
Mol. Cancer Ther.
7
143-151
2008
Homo sapiens
Manually annotated by BRENDA team
Reyes, D.Y.; Zuber, P.
Activation of transcription initiation by Spx: formation of transcription complex and identification of a Cis-acting element required for transcriptional activation
Mol. Microbiol.
69
765-779
2008
Rattus norvegicus (O89049), Homo sapiens (Q16881)
Manually annotated by BRENDA team
Zamudio, S.; Kovalenko, O.; Vanderlelie, J.; Illsley, N.P.; Heller, D.; Belliappa, S.; Perkins, A.V.
Chronic hypoxia in vivo reduces placental oxidative stress
Placenta
28
846-853
2007
Homo sapiens
Manually annotated by BRENDA team
Yoo, M.H.; Xu, X.M.; Carlson, B.A.; Patterson, A.D.; Gladyshev, V.N.; Hatfield, D.L.
Targeting thioredoxin reductase 1 reduction in cancer cells inhibits self-sufficient growth and DNA replication
PLoS ONE
2
e1112
2007
Homo sapiens (Q16881), Mus musculus (Q9JMH6), Mus musculus
Manually annotated by BRENDA team
Anestal, K.; Prast-Nielsen, S.; Cenas, N.; Arner, E.S.
Cell death by SecTRAPs: thioredoxin reductase as a prooxidant killer of cells
PLoS ONE
3
e1846
2008
Homo sapiens, Rattus norvegicus (O89049)
Manually annotated by BRENDA team
Lu, J.; Chew, E.H.; Holmgren, A.
Targeting thioredoxin reductase is a basis for cancer therapy by arsenic trioxide
Proc. Natl. Acad. Sci. USA
104
12288-12293
2007
Homo sapiens
Manually annotated by BRENDA team
Arner, E.S.
Focus on mammalian thioredoxin reductases--important selenoproteins with versatile functions
Biochim. Biophys. Acta
1790
495-526
2009
Homo sapiens, Mus musculus (Q9JLT4), Mus musculus (Q9JMH6), Mus musculus
Manually annotated by BRENDA team
Du, Y.; Wu, Y.; Cao, X.; Cui, W.; Zhang, H.; Tian, W.; Ji, M.; Holmgren, A.; Zhong, L.
Inhibition of mammalian thioredoxin reductase by black tea and its constituents: implications for anticancer actions
Biochimie
91
434-444
2009
Bos taurus (O62768), Homo sapiens (Q16881)
Manually annotated by BRENDA team
Volonte, D.; Galbiati, F.
Inhibition of thioredoxin reductase 1 by caveolin 1 promotes stress-induced premature senescence
EMBO Rep.
10
1334-1340
2009
Mus musculus, Homo sapiens (Q16881)
Manually annotated by BRENDA team
Eriksson, S.E.; Prast-Nielsen, S.; Flaberg, E.; Szekely, L.; Arner, E.S.
High levels of thioredoxin reductase 1 modulate drug-specific cytotoxic efficacy
Free Radic. Biol. Med.
47
1661-1671
2009
Rattus norvegicus (O89049), Homo sapiens (Q16881), Homo sapiens
Manually annotated by BRENDA team
Chew, E.H.; Nagle, A.A.; Zhang, Y.; Scarmagnani, S.; Palaniappan, P.; Bradshaw, T.D.; Holmgren, A.; Westwell, A.D.
Cinnamaldehydes inhibit thioredoxin reductase and induce Nrf2: potential candidates for cancer therapy and chemoprevention
Free Radic. Biol. Med.
48
98-111
2010
Escherichia coli, Homo sapiens, Rattus norvegicus
Manually annotated by BRENDA team
Tibodeau, J.; Benson, L.; Isham, C.; Owen, W.; Bible, K.
The anticancer agent chaetocin is a competitive substrate and inhibitor of thioredoxin reductase
Antioxid. Redox Signal.
11
1097-1106
2009
Homo sapiens
Manually annotated by BRENDA team
Liu, Z.B.; Shen, X.
Thioredoxin reductase 1 upregulates MCP-1 release in human endothelial cells
Biochem. Biophys. Res. Commun.
386
703-708
2009
Homo sapiens
Manually annotated by BRENDA team
Turanov, A.A.; Kehr, S.; Marino, S.M.; Yoo, M.H.; Carlson, B.A.; Hatfield, D.L.; Gladyshev, V.N.
Mammalian thioredoxin reductase 1: roles in redox homoeostasis and characterization of cellular targets
Biochem. J.
430
285-293
2010
Mus musculus, Rattus norvegicus (O89049), Homo sapiens (Q16881)
Manually annotated by BRENDA team
Damdimopoulou, P.E.; Miranda-Vizuete, A.; Arner, E.S.; Gustafsson, J.A.; Damdimopoulos, A.E.
The human thioredoxin reductase-1 splice variant TXNRD1_v3 is an atypical inducer of cytoplasmic filaments and cell membrane filopodia
Biochim. Biophys. Acta
1793
1588-1596
2009
Homo sapiens
Manually annotated by BRENDA team
Javvadi, P.; Hertan, L.; Kosoff, R.; Datta, T.; Kolev, J.; Mick, R.; Tuttle, S.W.; Koumenis, C.
Thioredoxin reductase-1 mediates curcumin-induced radiosensitization of squamous carcinoma cells
Cancer Res.
70
1941-1950
2010
Homo sapiens
Manually annotated by BRENDA team
Vergara, E.; Casini, A.; Sorrentino, F.; Zava, O.; Cerrada, E.; Rigobello, M.P.; Bindoli, A.; Laguna, M.; Dyson, P.J.
Anticancer therapeutics that target selenoenzymes: synthesis, characterization, in vitro cytotoxicity, and thioredoxin reductase inhibition of a series of gold(I) complexes containing hydrophilic phosphine ligands
ChemMedChem
5
96-102
2010
Homo sapiens
Manually annotated by BRENDA team
Carvalho, C.M.; Lu, J.; Zhang, X.; Arner, E.S.; Holmgren, A.
Effects of selenite and chelating agents on mammalian thioredoxin reductase inhibited by mercury: implications for treatment of mercury poisoning
FASEB J.
25
370-381
2011
Homo sapiens, Rattus norvegicus
Manually annotated by BRENDA team
Myers, J.M.; Myers, C.R.
The effects of hexavalent chromium on thioredoxin reductase and peroxiredoxins in human bronchial epithelial cells
Free Radic. Biol. Med.
47
1477-1485
2009
Homo sapiens
Manually annotated by BRENDA team
Prast-Nielsen, S.; Cebula, M.; Pader, I.; Arner, E.S.
Noble metal targeting of thioredoxin reductase--covalent complexes with thioredoxin and thioredoxin-related protein of 14 kDa triggered by cisplatin
Free Radic. Biol. Med.
49
1765-1778
2010
Homo sapiens, Rattus norvegicus
Manually annotated by BRENDA team
Lo, Y.C.; Ko, T.P.; Su, W.C.; Su, T.L.; Wang, A.H.
Terpyridine-platinum(II) complexes are effective inhibitors of mammalian topoisomerases and human thioredoxin reductase 1
J. Inorg. Biochem.
103
1082-1092
2009
Homo sapiens (Q16881), Homo sapiens
Manually annotated by BRENDA team
Turanov, A.A.; Hatfield, D.L.; Gladyshev, V.N.
Characterization of protein targets of mammalian thioredoxin reductases
Methods Enzymol.
474
245-254
2010
Homo sapiens, Mus musculus, Rattus norvegicus
Manually annotated by BRENDA team
Yan, C.; Shieh, B.; Reigan, P.; Zhang, Z.; Colucci, M.A.; Chilloux, A.; Newsome, J.J.; Siegel, D.; Chan, D.; Moody, C.J.; Ross, D.
Potent activity of indolequinones against human pancreatic cancer: identification of thioredoxin reductase as a potential target
Mol. Pharmacol.
76
163-172
2009
Homo sapiens, Rattus norvegicus
Manually annotated by BRENDA team
Yuan, L.; Kim, H.
Characterization of human cytosolic thioredoxin reductase by site-specific mutagenesis
Bull. Korean Chem. Soc.
31
3515-3516
2010
Homo sapiens
-
Manually annotated by BRENDA team
Rackham, O.; Shearwood, A.M.; Thyer, R.; McNamara, E.; Davies, S.M.; Callus, B.A.; Miranda-Vizuete, A.; Berners-Price, S.J.; Cheng, Q.; Arner, E.S.; Filipovska, A.
Substrate and inhibitor specificities differ between human cytosolic and mitochondrial thioredoxin reductases: Implications for development of specific inhibitors
Free Radic. Biol. Med.
50
689-699
2011
Homo sapiens
Manually annotated by BRENDA team
Qin, H.; Liang, W.; Xu, Z.; Ye, F.; Li, X.; Zhong, L.
Mechanistic insights into the inhibitory effects of palmitoylation on cytosolic thioredoxin reductase and thioredoxin
Biochimie
110
25-35
2015
Homo sapiens (Q16881), Homo sapiens
Manually annotated by BRENDA team
Wang, P.; Wu, Y.; Li, X.; Ma, X.; Zhong, L.
Thioredoxin and thioredoxin reductase control tissue factor activity by thiol redox-dependent mechanism
J. Biol. Chem.
288
3346-3358
2013
Homo sapiens (Q16881)
-
Manually annotated by BRENDA team
Ren, X.; Zou, L.; Lu, J.; Holmgren, A.
Selenocysteine in mammalian thioredoxin reductase and application of ebselen as a therapeutic
Free Radic. Biol. Med.
127
238-247
2018
Escherichia coli, Homo sapiens (Q86VQ6), Homo sapiens (Q9NNW7)
Manually annotated by BRENDA team
Cao, X.; Lilla, S.; Cao, Z.; Pringle, M.A.; Oka, O.B.V.; Robinson, P.J.; Szmaja, T.; van Lith, M.; Zanivan, S.; Bulleid, N.J.
The mammalian cytosolic thioredoxin reductase pathway acts via a membrane protein to reduce ER-localised proteins
J. Cell Sci.
133
jcs241976
2020
Homo sapiens (Q16881)
Manually annotated by BRENDA team