glutaredoxin-2, mitochondrial (GLRX2, GRX2, CGI-133)

Function: 1) glutathione-dependent oxidoreductase 2) facilitates maintenance of mitochondrial redox homeostasis upon induction of apoptosis by oxidative stress 3) role in response to hydrogen peroxide & regulation of apoptosis caused by oxidative stress 4) very efficient catalyst of monothiol reactions because of its high affinity for protein glutathione-mixed disulfides 5) can receive electrons not only from glutathione (GSH), but also from thioredoxin reductase supporting both monothiol & dithiol reactions 6) efficiently catalyzes both glutathionylation & deglutathionylation of mitochondrial complex 1, which in turn regulates the superoxide production by the complex 7) overexpression decreases the susceptibility to apoptosis & prevents loss of cardiolipin & cytochrome c release 8) 2Fe-2S present in the homodimer - leads to inactivation of the enzyme - may serve as a redox sensor: - presence of one-electron oxidants or reductants lead to loss of the 2Fe-2S cluster, subsequent monomerization & activation of the enzyme 9) unlike other glutaredoxins, not inhibited by oxidation of structural Cys residues Kinetic parameters: - KM=5.9 mM for GSH - KM=0.77 mM for glutathionylated ribonuclease A Structure: - monomer, active form - homodimer, inactive form, - homodimer is probably linked by 1 2Fe-2S cluster - - belongs to the glutaredoxin family Compartment: - isoform 1: mitochondrion - isoform 2: nucleus Alternative splicing: named isoforms=2 Expression: - widely expressed - expressed in brain, heart, skeletal muscle, colon, thymus, spleen, kidney, liver, small intestine, placenta, lung - not expressed in peripheral blood leukocytes Pathology: - absence of GLRX2 sensitizes cells to cell death induced by doxorubicin/adriamycin & phenylarsine oxide

General

mitochondrial protein oxidoreductase

Properties

SIZE: MW = 18 kD entity length = 164 aa COMPARTMENT: mitochondria cell nucleus MOTIF: cofactor-binding site [68-68] COFACTOR-BOUND: iron sulfur [FeS] cluster binding site SITE: 74-74 FOR-BINDING-OF: glutathione binding site SITE: 77-77 FOR-BINDING-OF: glutathione MOTIF: cysteine residue {C77} MODIFICATION: cysteine residue {C80} cysteine residue {C80} MODIFICATION: cysteine residue {C77} binding site SITE: 109-109 FOR-BINDING-OF: Glutathione binding site SITE: 121-121 FOR-BINDING-OF: glutathione binding site SITE: 134-135 FOR-BINDING-OF: Glutathione binding cofactor-binding site [153-153] COFACTOR-BOUND: iron sulfur [FeS] cluster

Database Correlations

OMIM 606820 UniProt Q9NS18 Pfam PF00462

References

UniProt :accession Q9NS18