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8-oxoguanine DNA glycosylase

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Target id: 3060

Nomenclature: 8-oxoguanine DNA glycosylase

Family: DNA glycosylases

Contents:

Gene and Protein Information Click here for help
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human - 345 3p25.3 OGG1 8-oxoguanine DNA glycosylase
Mouse - 345 6 52.75 cM Ogg1 8-oxoguanine DNA-glycosylase 1
Rat - 345 4q42 Ogg1 8-oxoguanine DNA glycosylase
Gene and Protein Information Comments
Many alternative splice variants for the human gene have been described. The predominant human transcript is variant 1a that gives rise to protein isoform 1a (345 amino acids).
Previous and Unofficial Names Click here for help
8-hydroxyguanine DNA glycosylase | HMMH | MUTM | OGH1
Database Links Click here for help
Alphafold O15527 (Hs), O08760 (Mm), O70249 (Rn)
ChEMBL Target CHEMBL3396944 (Hs)
Ensembl Gene ENSG00000114026 (Hs), ENSMUSG00000030271 (Mm), ENSRNOG00000052140 (Rn)
Entrez Gene 4968 (Hs), 18294 (Mm), 81528 (Rn)
Human Protein Atlas ENSG00000114026 (Hs)
KEGG Gene hsa:4968 (Hs), mmu:18294 (Mm), rno:81528 (Rn)
OMIM 601982 (Hs)
Pharos O15527 (Hs)
RefSeq Nucleotide NM_002542 (Hs), NM_010957 (Mm), NM_030870 (Rn)
RefSeq Protein NP_00253 (Hs), NP_035087 (Mm), NP_110497 (Rn)
UniProtKB O15527 (Hs), O08760 (Mm), O70249 (Rn)
Wikipedia OGG1 (Hs)

Download all structure-activity data for this target as a CSV file go icon to follow link

Inhibitors
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Reference
TH5487 Small molecule or natural product Ligand has a PDB structure Immunopharmacology Ligand Hs Binding - - 6
⤷ [6]
Immunopharmacology Comments
OGG1 has recognised roles in processes that are associated with innate and adaptive immunity [1-2], particulary as an initiator of proinflammtory responses [1]. At least some of OGG1's actions in the immune system and inflammation are related to its ability to recruit site-specific transcription factors and modulate the expression of genes that are involved in the producation of chemokines/cytokines and the activation/recruitment of inflammatory cells, in order to mount an effective innate immune response. As a result, pharmacological OGG1 inhibition is being explored as a novel antiinflammatory mechanism.
Immuno Process Associations
Immuno Process:  Inflammation
Physiological Consequences of Altering Gene Expression Click here for help
Ogg1-deficient mice are viable and largely healthy, but exhibit resistance to acute and systemic inflammation.
Species:  Mouse
Tissue: 
Technique: 
References:  3-5
General Comments
The OGG1 enzyme is responsible for the excision of 8-oxoguanine from oxidatively-damaged DNA. It is located intracellularly to mitochondria. OGG1 has also been identified as a transcription modulator, that can regulate transcription factor homing, recruit chromatin remodelers and induce downstream signaling cascades that alter gene expression.

References

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1. Aguilera-Aguirre L, Bacsi A, Radak Z, Hazra TK, Mitra S, Sur S, Brasier AR, Ba X, Boldogh I. (2014) Innate inflammation induced by the 8-oxoguanine DNA glycosylase-1-KRAS-NF-κB pathway. J Immunol, 193 (9): 4643-53. [PMID:25267977]

2. Ba X, Bacsi A, Luo J, Aguilera-Aguirre L, Zeng X, Radak Z, Brasier AR, Boldogh I. (2014) 8-oxoguanine DNA glycosylase-1 augments proinflammatory gene expression by facilitating the recruitment of site-specific transcription factors. J Immunol, 192 (5): 2384-94. [PMID:24489103]

3. Bacsi A, Aguilera-Aguirre L, Szczesny B, Radak Z, Hazra TK, Sur S, Ba X, Boldogh I. (2013) Down-regulation of 8-oxoguanine DNA glycosylase 1 expression in the airway epithelium ameliorates allergic lung inflammation. DNA Repair (Amst.), 12 (1): 18-26. [PMID:23127499]

4. Li G, Yuan K, Yan C, Fox 3rd J, Gaid M, Breitwieser W, Bansal AK, Zeng H, Gao H, Wu M. (2012) 8-Oxoguanine-DNA glycosylase 1 deficiency modifies allergic airway inflammation by regulating STAT6 and IL-4 in cells and in mice. Free Radic Biol Med, 52 (2): 392-401. [PMID:22100973]

5. Touati E, Michel V, Thiberge JM, Avé P, Huerre M, Bourgade F, Klungland A, Labigne A. (2006) Deficiency in OGG1 protects against inflammation and mutagenic effects associated with H. pylori infection in mouse. Helicobacter, 11 (5): 494-505. [PMID:16961812]

6. Visnes T, Cázares-Körner A, Hao W, Wallner O, Masuyer G, Loseva O, Mortusewicz O, Wiita E, Sarno A, Manoilov A et al.. (2018) Small-molecule inhibitor of OGG1 suppresses proinflammatory gene expression and inflammation. Science, 362 (6416): 834-839. [PMID:30442810]

How to cite this page

DNA glycosylases: 8-oxoguanine DNA glycosylase. Last modified on 16/01/2019. Accessed on 18/04/2024. IUPHAR/BPS Guide to PHARMACOLOGY, https://www.guidetomalariapharmacology.org/GRAC/ObjectDisplayForward?objectId=3060.