GLRX2 Human
Description
Molecular Overview of GLRX2
Gene and Protein Structure
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Gene Location: Chromosome 1q31.2–31.3, spanning 10 kilobase pairs with four exons and three introns .
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Isoforms: Alternative splicing produces three isoforms:
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Active Site: Contains a thioredoxin-like domain with a unique Cys-Ser-Tyr-Cys motif (residues 37–40), enabling flexibility for glutathione binding and iron-sulfur cluster coordination .
Redox Homeostasis and Antioxidant Defense
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Catalyzes protein deglutathionylation and reduces oxidized thioredoxins (Trx1/Trx2) .
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Protects mitochondrial complex I from oxidative inhibition, preserving electron transport chain integrity .
Apoptosis Regulation
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Overexpression reduces H₂O₂-, doxorubicin-, and ischemia-induced apoptosis by inhibiting cardiolipin oxidation and cytochrome c release .
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Knockout models exhibit sensitization to oxidative stress and impaired ATP production .
Clinical and Pathological Significance
Cancer
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Tumor Progression: Grx2b/c isoforms promote cellular differentiation and transformation in cancer cell lines .
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Biomarker Potential: Inverse correlation between Grx2 levels and proliferation in non-small cell lung adenocarcinoma .
Cardiovascular Disease
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Cardioprotection: Grx2a mitigates doxorubicin-induced cardiac injury by enhancing mitochondrial protein glutathionylation .
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Hypertension: Glrx2⁻/⁻ mice develop left ventricular hypertrophy and fibrosis .
Liver Injury
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Acetaminophen Toxicity: Glrx2 deficiency exacerbates liver damage (↑ ALT/AST) by disrupting glutathione homeostasis and Nrf2 signaling .
Table 1: Experimental Insights into GLRX2 Function
Table 2: Protein Interaction Network
| Interacting Partner | Functional Role | Pathway Association |
|---|---|---|
| TXNRD1 | Electron donor for Grx2 reduction | Thioredoxin antioxidant |
| CYCS | Apoptosis regulation | Mitochondrial permeability |
| GPX4 | Lipid peroxidation inhibition | Ferroptosis suppression |
| MDH2 | Metabolic enzyme regulation | TCA cycle |
Mechanisms of Redox Regulation
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Iron-Sulfur Cluster Dynamics:
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Glutathionylation Cycle:
Therapeutic Implications
Product Specs
Thioltransferase, Glutathione-dependent oxidoreductase 2, TTR, TTR1, GLRX2, GRX2, GRX-2, GLRX-2, Glutaredoxin 2, CGI133.
MSAGWLDRAA GAAGAAAAAA SGMESNTSSS LENLATAPVN QIQETISDNC VVIFSKTSCS YCTMAKKLFH DMNVNYKVVE LDLLEYGNQF QDALYKMTGE RTVPRIFVNG TFIGGATDTH RLHKEGKLLP LVHQCYLKKS KRKEFQLEHH HHHH.
Product Science Overview
GLRX2 catalyzes the formation and glutathionylation of disulfide bonds in proteins, particularly complex I. This reversible process is essential for maintaining the equilibrium between the mitochondrial glutathione pool and protein thiols, thereby regulating the mitochondrial response to redox signals and oxidative stress . Unlike GRX1, GRX2 is not inhibited by the oxidation of structural cysteine residues and can receive electrons from both glutathione (GSH) and thioredoxin reductase, supporting both monothiol and dithiol reactions .
GLRX2 is involved in the cellular response to apoptotic stimuli and oxidative stress at the mitochondrial checkpoint . It has been used in various biochemical assays, including the 2-oxoglutarate dehydrogenase (Ogdh) activity reaction . The enzyme’s ability to catalyze reversible protein glutathionylation/deglutathionylation under varying GSH/GSSG ratios makes it a valuable tool in studying redox biology and mitochondrial function .
Human recombinant GLRX2 is typically produced in Escherichia coli (E. coli) and is available in various forms, including a non-glycosylated polypeptide chain containing 154 amino acids with a molecular mass of 17 kDa . The recombinant protein is often fused to a His tag at the C-terminus for purification purposes .
