Target Information
Target General Information | Top | |||||
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Target ID |
T74425
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Target Name |
Glutaredoxin-2 (GLRX2)
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Synonyms |
Glutaredoxin-2, mitochondrial; GRX2; CGI-133
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Gene Name |
GLRX2
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Target Type |
Literature-reported target
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[1] | ||||
Function |
Glutathione-dependent oxidoreductase that facilitates the maintenance of mitochondrial redox homeostasis upon induction of apoptosis by oxidative stress. Involved in response to hydrogen peroxide and regulation of apoptosis caused by oxidative stress. Acts as a very efficient catalyst of monothiol reactions because of its high affinity for protein glutathione-mixed disulfides. Can receive electrons not only from glutathione (GSH), but also from thioredoxin reductase supporting both monothiol and dithiol reactions. Efficiently catalyzes both glutathionylation and deglutathionylation of mitochondrial complex I, which in turn regulates the superoxide production by the complex. Overexpression decreases the susceptibility to apoptosis and prevents loss of cardiolipin and cytochrome c release.
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UniProt ID | ||||||
Sequence |
MIWRRAALAGTRLVWSRSGSAGWLDRAAGAAGAAAAAASGMESNTSSSLENLATAPVNQI
QETISDNCVVIFSKTSCSYCTMAKKLFHDMNVNYKVVELDLLEYGNQFQDALYKMTGERT VPRIFVNGTFIGGATDTHRLHKEGKLLPLVHQCYLKKSKRKEFQ Click to Show/Hide
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3D Structure | Click to Show 3D Structure of This Target | AlphaFold |
Cell-based Target Expression Variations | Top | |||||
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Cell-based Target Expression Variations |
Drug Binding Sites of Target | Top | |||||
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Ligand Name: Glutathione | Ligand Info | |||||
Structure Description | The structure of dimeric human glutaredoxin 2 | PDB:2HT9 | ||||
Method | X-ray diffraction | Resolution | 1.90 Å | Mutation | No | [2] |
PDB Sequence |
LATAPVNQIQ
21 ETISDNCVVI31 FSKTSCSYCT41 MAKKLFHDMN51 VNYKVVELDL61 LEYGNQFQDA 71 LYKMTGERTV81 PRIFVNGTFI91 GGATDTHRLH101 KEGKLLPLVH111 QCYL |
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Click to View More Binding Site Information of This Target and Ligand Pair | ||||||
Click to View More Binding Site Information of This Target with Different Ligands |
Different Human System Profiles of Target | Top |
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Human Similarity Proteins
of target is determined by comparing the sequence similarity of all human proteins with the target based on BLAST. The similarity proteins for a target are defined as the proteins with E-value < 0.005 and outside the protein families of the target.
A target that has fewer human similarity proteins outside its family is commonly regarded to possess a greater capacity to avoid undesired interactions and thus increase the possibility of finding successful drugs
(Brief Bioinform, 21: 649-662, 2020).
Human Tissue Distribution
of target is determined from a proteomics study that quantified more than 12,000 genes across 32 normal human tissues. Tissue Specificity (TS) score was used to define the enrichment of target across tissues.
The distribution of targets among different tissues or organs need to be taken into consideration when assessing the target druggability, as it is generally accepted that the wider the target distribution, the greater the concern over potential adverse effects
(Nat Rev Drug Discov, 20: 64-81, 2021).
Human Similarity Proteins
Human Tissue Distribution
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There is no similarity protein (E value < 0.005) for this target
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Note:
If a protein has TS (tissue specficity) scores at least in one tissue >= 2.5, this protein is called tissue-enriched (including tissue-enriched-but-not-specific and tissue-specific). In the plots, the vertical lines are at thresholds 2.5 and 4.
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References | Top | |||||
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REF 1 | Characterization of the impact of glutaredoxin-2 (GRX2) deficiency on superoxide/hydrogen peroxide release from cardiac and liver mitochondria. Redox Biol. 2018 May;15:216-227. | |||||
REF 2 | Reversible sequestration of active site cysteines in a 2Fe-2S-bridged dimer provides a mechanism for glutaredoxin 2 regulation in human mitochondria. J Biol Chem. 2007 Feb 2;282(5):3077-82. |
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