BRENDA - Enzyme Database
show all sequences of 1.8.1.6

Thioredoxin-related protein of 14 kDa is an efficient L-cystine reductase and S-denitrosylase

Pader, I.; Sengupta, R.; Cebula, M.; Xu, J.; Lundberg, J.O.; Holmgren, A.; Johansson, K.; Arner, E.S.; Proc. Natl. Acad. Sci. USA 111, 6964-6969 (2014)

Data extracted from this reference:

Cloned(Commentary)
Cloned (Commentary)
Organism
recombinant expression of wild-type and mutant enzymes in Escherichia coli strain BL21(DE3)
Homo sapiens
Engineering
Protein Variants
Commentary
Organism
C43S/C46S
site-directed mutagenesis, inactive mutant
Homo sapiens
C46S
site-directed mutagenesis, the mutant shows reduced activity compared to the wild-type enzyme
Homo sapiens
additional information
knockdown and overexpression of TRP14 affect total L-cystine reduction capacity and S-nitrosoprotein levels in crude HEK-293 cell lysate
Homo sapiens
KM Value [mM]
KM Value [mM]
KM Value Maximum [mM]
Substrate
Commentary
Organism
Structure
additional information
-
additional information
Michaelis-Menten kinetics
Homo sapiens
0.0008
-
L-cystine
pH 7.5, 22C, wild-type enzyme TRP14
Homo sapiens
Localization
Localization
Commentary
Organism
GeneOntology No.
Textmining
cytosol
-
Homo sapiens
5829
-
Natural Substrates/ Products (Substrates)
Natural Substrates
Organism
Commentary (Nat. Sub.)
Natural Products
Commentary (Nat. Pro.)
Organism (Nat. Pro.)
Reversibility
ID
L-cystine + NADH + H+
Homo sapiens
-
2 L-cysteine + NAD+
-
-
?
additional information
Homo sapiens
enzyme TRP14 not being able to reduce any classical protein disulfide substrates of thioredoxin 1, Trx1. Trx1-mediated L-cystine reduction is inefficient in the presence of other preferred Trx1 substrates whereas, conversely, TRP14 seems to be a more dedicated L-cystine reductase
?
-
-
-
Organism
Organism
UniProt
Commentary
Textmining
Homo sapiens
Q9BRA2
-
-
Purification (Commentary)
Purification (Commentary)
Organism
recombinant wild-type and mutant enzymes from Escherichia coli strain Bl21(DE3)
Homo sapiens
Source Tissue
Source Tissue
Commentary
Organism
Textmining
A-431 cell
high enzyme expression level
Homo sapiens
-
HEK-293 cell
-
Homo sapiens
-
Substrates and Products (Substrate)
Substrates
Commentary Substrates
Literature (Substrates)
Organism
Products
Commentary (Products)
Literature (Products)
Organism (Products)
Reversibility
Substrate Product ID
L-cystine + NADH + H+
-
743682
Homo sapiens
2 L-cysteine + NAD+
-
-
-
?
additional information
enzyme TRP14 not being able to reduce any classical protein disulfide substrates of thioredoxin 1, Trx1. Trx1-mediated L-cystine reduction is inefficient in the presence of other preferred Trx1 substrates whereas, conversely, TRP14 seems to be a more dedicated L-cystine reductase
743682
Homo sapiens
?
-
-
-
-
additional information
enzyme TRP14 has S-denitrosylase activity performing GSNO reduction with realease of NO, it is also active with L-CysSNO
743682
Homo sapiens
?
-
-
-
-
Synonyms
Synonyms
Commentary
Organism
L-cystine reductase
-
Homo sapiens
thioredoxin domain containing 17
-
Homo sapiens
thioredoxin-like 5
-
Homo sapiens
TRP14
-
Homo sapiens
TXNDC17
-
Homo sapiens
TXNL5
-
Homo sapiens
Temperature Optimum [C]
Temperature Optimum [C]
Temperature Optimum Maximum [C]
Commentary
Organism
22
-
assay at room temperature
Homo sapiens
Turnover Number [1/s]
Turnover Number Minimum [1/s]
Turnover Number Maximum [1/s]
Substrate
Commentary
Organism
Structure
30.3
-
L-cystine
pH 7.5, 22C, wild-type enzyme TRP14
Homo sapiens
pH Optimum
pH Optimum Minimum
pH Optimum Maximum
Commentary
Organism
7.5
-
assay at
Homo sapiens
Cofactor
Cofactor
Commentary
Organism
Structure
NADH
-
Homo sapiens
Cloned(Commentary) (protein specific)
Commentary
Organism
recombinant expression of wild-type and mutant enzymes in Escherichia coli strain BL21(DE3)
Homo sapiens
Cofactor (protein specific)
Cofactor
Commentary
Organism
Structure
NADH
-
Homo sapiens
Engineering (protein specific)
Protein Variants
Commentary
Organism
C43S/C46S
site-directed mutagenesis, inactive mutant
Homo sapiens
C46S
site-directed mutagenesis, the mutant shows reduced activity compared to the wild-type enzyme
Homo sapiens
additional information
knockdown and overexpression of TRP14 affect total L-cystine reduction capacity and S-nitrosoprotein levels in crude HEK-293 cell lysate
Homo sapiens
KM Value [mM] (protein specific)
KM Value [mM]
KM Value Maximum [mM]
Substrate
Commentary
Organism
Structure
additional information
-
additional information
Michaelis-Menten kinetics
Homo sapiens
0.0008
-
L-cystine
pH 7.5, 22C, wild-type enzyme TRP14
Homo sapiens
Localization (protein specific)
Localization
Commentary
Organism
GeneOntology No.
Textmining
cytosol
-
Homo sapiens
5829
-
Natural Substrates/ Products (Substrates) (protein specific)
Natural Substrates
Organism
Commentary (Nat. Sub.)
Natural Products
Commentary (Nat. Pro.)
Organism (Nat. Pro.)
Reversibility
ID
L-cystine + NADH + H+
Homo sapiens
-
2 L-cysteine + NAD+
-
-
?
additional information
Homo sapiens
enzyme TRP14 not being able to reduce any classical protein disulfide substrates of thioredoxin 1, Trx1. Trx1-mediated L-cystine reduction is inefficient in the presence of other preferred Trx1 substrates whereas, conversely, TRP14 seems to be a more dedicated L-cystine reductase
?
-
-
-
Purification (Commentary) (protein specific)
Commentary
Organism
recombinant wild-type and mutant enzymes from Escherichia coli strain Bl21(DE3)
Homo sapiens
Source Tissue (protein specific)
Source Tissue
Commentary
Organism
Textmining
A-431 cell
high enzyme expression level
Homo sapiens
-
HEK-293 cell
-
Homo sapiens
-
Substrates and Products (Substrate) (protein specific)
Substrates
Commentary Substrates
Literature (Substrates)
Organism
Products
Commentary (Products)
Literature (Products)
Organism (Products)
Reversibility
ID
L-cystine + NADH + H+
-
743682
Homo sapiens
2 L-cysteine + NAD+
-
-
-
?
additional information
enzyme TRP14 not being able to reduce any classical protein disulfide substrates of thioredoxin 1, Trx1. Trx1-mediated L-cystine reduction is inefficient in the presence of other preferred Trx1 substrates whereas, conversely, TRP14 seems to be a more dedicated L-cystine reductase
743682
Homo sapiens
?
-
-
-
-
additional information
enzyme TRP14 has S-denitrosylase activity performing GSNO reduction with realease of NO, it is also active with L-CysSNO
743682
Homo sapiens
?
-
-
-
-
Temperature Optimum [C] (protein specific)
Temperature Optimum [C]
Temperature Optimum Maximum [C]
Commentary
Organism
22
-
assay at room temperature
Homo sapiens
Turnover Number [1/s] (protein specific)
Turnover Number Minimum [1/s]
Turnover Number Maximum [1/s]
Substrate
Commentary
Organism
Structure
30.3
-
L-cystine
pH 7.5, 22C, wild-type enzyme TRP14
Homo sapiens
pH Optimum (protein specific)
pH Optimum Minimum
pH Optimum Maximum
Commentary
Organism
7.5
-
assay at
Homo sapiens
General Information
General Information
Commentary
Organism
evolution
the enzyme belongs to the member of the thioredoxin (Trx)-fold protein family. The enzyme lacks activity with classical thioredoxin, Trx1, substrates. Human enzyme TRP14 has high enzymatic activity in reduction of L-cystine, where the catalytic efficiency coupled to Trx reductase 1 (TrxR1) using NADPH is fivefold higher than the activity of enzyme Trx1 alone. Trx1-mediated L-cystine reduction is inefficient in the presence of other preferred Trx1 substrates whereas, conversely, TRP14 seems to be a more dedicated L-cystine reductase
Homo sapiens
additional information
the disulfide/dithiol motif formed by Cys43 and Cys46 is the active site of TRP14
Homo sapiens
General Information (protein specific)
General Information
Commentary
Organism
evolution
the enzyme belongs to the member of the thioredoxin (Trx)-fold protein family. The enzyme lacks activity with classical thioredoxin, Trx1, substrates. Human enzyme TRP14 has high enzymatic activity in reduction of L-cystine, where the catalytic efficiency coupled to Trx reductase 1 (TrxR1) using NADPH is fivefold higher than the activity of enzyme Trx1 alone. Trx1-mediated L-cystine reduction is inefficient in the presence of other preferred Trx1 substrates whereas, conversely, TRP14 seems to be a more dedicated L-cystine reductase
Homo sapiens
additional information
the disulfide/dithiol motif formed by Cys43 and Cys46 is the active site of TRP14
Homo sapiens
KCat/KM [mM/s]
kcat/KM Value [1/mMs-1]
kcat/KM Value Maximum [1/mMs-1]
Substrate
Commentary
Organism
Structure
37875
-
L-cystine
pH 7.5, 22C, wild-type enzyme TRP14
Homo sapiens
KCat/KM [mM/s] (protein specific)
KCat/KM Value [1/mMs-1]
KCat/KM Value Maximum [1/mMs-1]
Substrate
Commentary
Organism
Structure
37875
-
L-cystine
pH 7.5, 22C, wild-type enzyme TRP14
Homo sapiens
Other publictions for EC
No.
1st author
Pub Med
title
organims
journal
volume
pages
year
Activating Compound
Application
Cloned(Commentary)
Crystallization (Commentary)
Engineering
General Stability
Inhibitors
KM Value [mM]
Localization
Metals/Ions
Molecular Weight [Da]
Natural Substrates/ Products (Substrates)
Organic Solvent Stability
Organism
Oxidation Stability
Posttranslational Modification
Purification (Commentary)
Reaction
Renatured (Commentary)
Source Tissue
Specific Activity [micromol/min/mg]
Storage Stability
Substrates and Products (Substrate)
Subunits
Synonyms
Temperature Optimum [C]
Temperature Range [C]
Temperature Stability [C]
Turnover Number [1/s]
pH Optimum
pH Range
pH Stability
Cofactor
Ki Value [mM]
pI Value
IC50 Value
Activating Compound (protein specific)
Application (protein specific)
Cloned(Commentary) (protein specific)
Cofactor (protein specific)
Crystallization (Commentary) (protein specific)
Engineering (protein specific)
General Stability (protein specific)
IC50 Value (protein specific)
Inhibitors (protein specific)
Ki Value [mM] (protein specific)
KM Value [mM] (protein specific)
Localization (protein specific)
Metals/Ions (protein specific)
Molecular Weight [Da] (protein specific)
Natural Substrates/ Products (Substrates) (protein specific)
Organic Solvent Stability (protein specific)
Oxidation Stability (protein specific)
Posttranslational Modification (protein specific)
Purification (Commentary) (protein specific)
Renatured (Commentary) (protein specific)
Source Tissue (protein specific)
Specific Activity [micromol/min/mg] (protein specific)
Storage Stability (protein specific)
Substrates and Products (Substrate) (protein specific)
Subunits (protein specific)
Temperature Optimum [C] (protein specific)
Temperature Range [C] (protein specific)
Temperature Stability [C] (protein specific)
Turnover Number [1/s] (protein specific)
pH Optimum (protein specific)
pH Range (protein specific)
pH Stability (protein specific)
pI Value (protein specific)
Expression
General Information
General Information (protein specific)
Expression (protein specific)
KCat/KM [mM/s]
KCat/KM [mM/s] (protein specific)
743682
Pader
Thioredoxin-related protein o ...
Homo sapiens
Proc. Natl. Acad. Sci. USA
111
6964-6969
2014
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1
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3
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2
1
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2
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2
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1
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2
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3
-
6
1
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1
1
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1
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1
1
-
3
-
-
-
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2
1
-
-
2
-
-
-
1
-
2
-
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3
-
1
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1
1
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-
-
-
2
2
-
1
1
673491
Ondarza
The effects by neuroleptics, a ...
Acanthamoeba polyphaga, Naegleria fowleri
Exp. Parasitol.
115
41-47
2007
4
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-
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11
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5
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2
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2
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4
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11
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2
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667725
Kim
Properties of the cysteine res ...
Ulva intestinalis
Biochemistry
45
5010-5018
2006
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1
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4
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1
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1
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1
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1
-
1
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-
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-
440354
Maresca
Cystine reductase in the dimor ...
Histoplasma capsulatum
J. Bacteriol.
135
987-992
1978
-
-
-
-
-
-
1
1
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1
-
3
-
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1
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2
-
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1
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1
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1
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1
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1
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1
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2
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440356
Carroll
alpha-Substituted cystines as ...
Saccharomyces cerevisiae
Biochim. Biophys. Acta
198
601-603
1970
-
-
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2
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1
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1
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1
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1
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2
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1
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440355
Thibert
-
Simultaneous determination of ...
Saccharomyces cerevisiae
Mikrochim. Acta
3
615-624
1969
-
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1
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1
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1
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1
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440353
Romano
Cystine reductase of pea seeds ...
Candida albicans, Pisum sativum, Saccharomyces cerevisiae
J. Biol. Chem.
208
409-416
1954
-
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-
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5
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3
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3
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