General Information:

Id: 14,377
Diseases: Metabolic
Homo sapiens
article
Reference: Johansson C et al.(2004) Human mitochondrial glutaredoxin reduces S-glutathionylated proteins with high affinity accepting electrons from either glutathione or thioredoxin reductase J Biol Chem 279: 7537-7543 [PMID: 14676218]

Interaction Information:

Comment Grx2 is a direct substrate for thioredoxin reductase and thus acts as a thioredoxin, being able to accept electrons from both TrxR1 and TrxR2 as well as from GSH. Using this novel electron donor pathway, Grx2 reduced low molecular weight disulfides such as CoA but with particular high efficiency glutathionylated substrates including GSSG. These results suggest an important role for Grx2 in protection and recovery from oxidative stress.
Formal Description
Interaction-ID: 135703

gene/protein

GLRX2

decreases_activity of

reducing low molecular weight disulfides such as CoA but with particular high efficiency glutathionylated substrates including GSSG; being able to accept electrons from both TrxR1 and TrxR2 as well as from GSH
Drugbank entries Show/Hide entries for GLRX2
Comment Since TrxR1 and TrxR2 from various species reveal almost identical kinetic parameters, one can expect human mitochondrial TrxR2 to reduce Grx2 with an efficiency similar to that of the bovine TrxR1. Activity with the monothiol active site mutant Grx2C40S, in a coupled assay with Cys-SG, demonstrated further that TrxR can support both monothiol and dithiol reactions catalyzed by Grx2. This suggests that the glutaredoxin-GSH-mixed disulfide is attacked by the selenolate in TrxR, forming a mixed disulfide intermediate, releasing the glutathione moiety, revealing a new glutathione-independent path of electron flow from NADPH to various Grx substrates.
Formal Description
Interaction-ID: 135704

gene/protein

GLRX2

interacts (colocalizes) with

gene/protein

TXNRD1

forming a mixed disulfide intermediate
Drugbank entries Show/Hide entries for GLRX2 or TXNRD1
Comment Complete Trx and the Grx systems in mammalian cells are present both in the cytosol and the mitochondria.
Formal Description
Interaction-ID: 135705

process

TRX system

is localized in

cellular component

mitochondrion

in mammalian cells
Comment Grx2 is a direct substrate for thioredoxin reductase and thus acts as a thioredoxin, being able to accept electrons from both TrxR1 and TrxR2 as well as from GSH. Using this novel electron donor pathway, Grx2 reduced low molecular weight disulfides such as CoA but with particular high efficiency glutathionylated substrates including GSSG. These results suggest an important role for Grx2 in protection and recovery from oxidative stress.
Formal Description
Interaction-ID: 135706

gene/protein

GLRX2

increases_activity of

being able to accept electrons from both TrxR1 and TrxR2 as well as from GSH
Drugbank entries Show/Hide entries for GLRX2
Comment Grx2 is a direct substrate for thioredoxin reductase and thus acts as a thioredoxin, being able to accept electrons from both TrxR1 and TrxR2 as well as from GSH. Using this novel electron donor pathway, Grx2 reduced low molecular weight disulfides such as CoA but with particular high efficiency glutathionylated substrates including GSSG. These results suggest an important role for Grx2 in protection and recovery from oxidative stress.
Formal Description
Interaction-ID: 135707

gene/protein

TXNRD1

increases_activity of

being able to accept electrons from both TrxR1 and TrxR2 as well as from GSH
Drugbank entries Show/Hide entries for TXNRD1
Comment Grx2 is a direct substrate for thioredoxin reductase and thus acts as a thioredoxin, being able to accept electrons from both TrxR1 and TrxR2 as well as from GSH. Using this novel electron donor pathway, Grx2 reduced low molecular weight disulfides such as CoA but with particular high efficiency glutathionylated substrates including GSSG. These results suggest an important role for Grx2 in protection and recovery from oxidative stress.
Formal Description
Interaction-ID: 135708

gene/protein

TXNRD2

increases_activity of

being able to accept electrons from both TrxR1 and TrxR2 as well as from GSH
Comment The results suggest an important role for Grx2 in protection and recovery from oxidative stress. In fact, Grx2 may be a key regulator of apoptosis via the mitochondrial checkpoint.
Formal Description
Interaction-ID: 135712

gene/protein

GLRX2

affects_activity of

via the mitochondrial checkpoint.
Drugbank entries Show/Hide entries for GLRX2
Comment Complete Trx and the Grx systems in mammalian cells are present both in the cytosol and the mitochondria.
Formal Description
Interaction-ID: 135713

process

GLRX system

is localized in

cellular component

mitochondrion

in mammalian cells
Comment Complete Trx and the Grx systems in mammalian cells are present both in the cytosol and the mitochondria.
Formal Description
Interaction-ID: 135714

process

TRX system

is localized in

cellular component

cytosol

in mammalian cells
Comment Complete Trx and the Grx systems in mammalian cells are present both in the cytosol and the mitochondria.
Formal Description
Interaction-ID: 135715

process

GLRX system

is localized in

cellular component

cytosol

in mammalian cells
Comment Grx (Grx2) is due to an alternative splicing mechanism targeted either to the nucleus or to mitochondria. Grx2 has a predicted size of 18 kDa and contains a CSYC active site motif that differs from the Grx consensus CPYC.
Formal Description
Interaction-ID: 135717

gene/protein

GLRX2

increases_activity of

process

GLRX system

Drugbank entries Show/Hide entries for GLRX2
Comment Grx (Grx2) is due to an alternative splicing mechanism targeted either to the nucleus or to mitochondria. Grx2 has a predicted size of 18 kDa and contains a CSYC active site motif that differs from the Grx consensus CPYC.
Formal Description
Interaction-ID: 135718

gene/protein

GLRX2

is localized in

cellular component

mitochondrion

Drugbank entries Show/Hide entries for GLRX2
Comment Grx (Grx2) is due to an alternative splicing mechanism targeted either to the nucleus or to mitochondria. Grx2 has a predicted size of 18 kDa and contains a CSYC active site motif that differs from the Grx consensus CPYC.
Formal Description
Interaction-ID: 135719

gene/protein

GLRX2

is localized in

cellular component

nucleus

Drugbank entries Show/Hide entries for GLRX2
Comment Grx (Grx2) is due to an alternative splicing mechanism targeted either to the nucleus or to mitochondria. Grx2 has a predicted size of 18 kDa and contains a CSYC active site motif that differs from the Grx consensus CPYC.
Formal Description
Interaction-ID: 135720

increases_quantity of

gene/protein

GLRX2 (nucleus)

Comment Grx (Grx2) is due to an alternative splicing mechanism targeted either to the nucleus or to mitochondria. Grx2 has a predicted size of 18 kDa and contains a CSYC active site motif that differs from the Grx consensus CPYC.
Formal Description
Interaction-ID: 135721

increases_quantity of

gene/protein

GLRX2 (mitochondrial)

Comment Grx (Grx2) is due to an alternative splicing mechanism targeted either to the nucleus or to mitochondria. Grx2 has a predicted size of 18 kDa and contains a CSYC active site motif that differs from the Grx consensus CPYC.
Formal Description
Interaction-ID: 135722

gene/protein

GLRX2 (mitochondrial)

affects_activity of

gene/protein

GLRX2

Drugbank entries Show/Hide entries for GLRX2
Comment Grx (Grx2) is due to an alternative splicing mechanism targeted either to the nucleus or to mitochondria. Grx2 has a predicted size of 18 kDa and contains a CSYC active site motif that differs from the Grx consensus CPYC.
Formal Description
Interaction-ID: 135723

gene/protein

GLRX2 (nucleus)

affects_activity of

gene/protein

GLRX2

Drugbank entries Show/Hide entries for GLRX2
Comment The thioredoxin system is composed of thioredoxin reductase (TrxR), in mammalian cells a selenocysteine-containing, dimeric nicotinamide nucleotide disulfide oxidoreductase, which reduces thioredoxin (Trx), the major protein disulfide reductase with a large number of functions in mammalian cells.
Formal Description
Interaction-ID: 135724

gene/protein

TXNRD1

increases_activity of

process

TRX system

Drugbank entries Show/Hide entries for TXNRD1
Comment The thioredoxin system is composed of thioredoxin reductase (TrxR), in mammalian cells a selenocysteine-containing, dimeric nicotinamide nucleotide disulfide oxidoreductase, which reduces thioredoxin (Trx), the major protein disulfide reductase with a large number of functions in mammalian cells.
Formal Description
Interaction-ID: 135725

gene/protein

TXNRD2

increases_activity of

process

TRX system

Comment The thioredoxin system is composed of thioredoxin reductase (TrxR), in mammalian cells a selenocysteine-containing, dimeric nicotinamide nucleotide disulfide oxidoreductase, which reduces thioredoxin (Trx), the major protein disulfide reductase with a large number of functions in mammalian cells.
Formal Description
Interaction-ID: 135726

gene/protein

TXNRD2

decreases_quantity of

drug/chemical compound

Thioredoxin

via reducing thioredoxin
Comment The thioredoxin system is composed of thioredoxin reductase (TrxR), in mammalian cells a selenocysteine-containing, dimeric nicotinamide nucleotide disulfide oxidoreductase, which reduces thioredoxin (Trx), the major protein disulfide reductase with a large number of functions in mammalian cells.
Formal Description
Interaction-ID: 135727

gene/protein

TXNRD1

decreases_quantity of

drug/chemical compound

Thioredoxin

via reducing thioredoxin
Drugbank entries Show/Hide entries for TXNRD1