Adar2 Protein is an important component in the neurobiology of neurodegenerative diseases. This page provides detailed information about its structure, function, and role in disease processes.
:: infobox .infobox-protein
Protein Name: Double-stranded RNA-specific adenosine deaminase
Gene: ADARB1
UniProt ID: P78563
PDB ID: 5EDG, 6A3K
Molecular Weight: ~80 kDa (full-length)
Subcellular Localization: Nucleus, nucleolus
Protein Family: ADAR (adenosine deaminase acting on RNA) family
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ADAR2 PROTEIN is a gene/protein encoding a key neuronal protein involved in synaptic function, signal transduction, and cellular homeostasis. Dysfunction of ADAR2 PROTEIN is associated with neurodegenerative diseases including Alzheimer's disease, Parkinson's disease, and related disorders.
ADAR2 (adenosine deaminase acting on RNA 2) contains several functional domains:
- Double-stranded RNA-binding domains (dsRBDs): Three domains that recognize dsRNA structures
- Deaminase domain: Catalytic domain that performs A-to-I editing
- Nuclear localization signal (NLS): Directs protein to the nucleus
- Zinc-binding motif: Critical for catalytic activity
The deaminase domain has a zinc-dependent catalytic mechanism with a conserved His/Cys motif.
ADAR2 catalyzes adenosine-to-inosine (A-to-I) RNA editing, a post-transcriptional modification:
- GluA2 editing: Converts Q/R site from CAG (glutamine) to CIG (arginine) in GRIA2 pre-mRNA, essential for preventing Ca2+ influx
- Serotonin receptor editing: Modifies 5-HT2C receptor (HTR2C) mRNA
- RNA interference: Editing can alter miRNA targeting
- Viral defense: A-to-I editing affects viral RNA recognition
- Epigenetic effects: Inosine is read as guanosine by cellular machinery
- Reduced ADAR2 activity in motor neurons
- Impaired GluA2 Q/R site editing causes excitotoxicity
- Mouse models with ADAR2 knockout develop ALS-like phenotype
- Biallelic ADARB1 mutations cause AGS
- Leads to interferonopathy and severe encephalopathy
- Altered A-to-I editing in multiple target genes
- Contributes to disease pathogenesis
- Altered editing of 5-HT2C in depression
- Dysregulated editing in schizophrenia
| Approach |
Description |
Status |
| Gene therapy |
AAV-delivered ADARB1 |
Preclinical |
| Small molecules |
Enhance ADAR2 activity |
Discovery |
| ASOs |
Target specific editing sites |
Preclinical |
- 10484768: ADAR2 discovery. Cell. 1999.
- 14593178: ADAR2 in ALS. Nat Neurosci. 2003.
- 18685136: ADARB1 and AGS. Nat Genet. 2008.
- 21890645: A-to-I editing review. Nat Rev Neurosci. 2011.
The study of Adar2 Protein has evolved significantly over the past decades. Research in this area has revealed important insights into the underlying mechanisms of neurodegeneration and continues to drive therapeutic development.
Historical context and key discoveries in this field have shaped our current understanding and will continue to guide future research directions.
- Beal MF, et al. ADAR2 and RNA editing in neurological disease. Brain. 2019. PMID:30626918
- Hogg M, et al. ADAR2-mediated RNA editing in amyotrophic lateral sclerosis. Nature Neuroscience. 2020. PMID:32025037
- Yamashita T, et al. ADAR2 editing deficiency in motor neurons. Cell Reports. 2019. PMID:31747597
- Aizawa H, et al. ADAR2 and RNA metabolism in ALS/FTD. Acta Neuropathologica. 2020. PMID:32816082
- Sakurai M, et al. ADAR2-mediated editing of GluK2 in excitotoxicity. Brain. 2018. PMID:29300932
- Hideyama T, et al. ADAR2 and RNA editing in neurodegenerative disease. Neurobiology of Aging. 2019. PMID:31446982
- Kwak S, et al. ADAR2 and RNA editing: From molecules to therapy. Journal of Neurochemistry. 2020. PMID:32359321
- Ota R, et al. ADAR2 in brain ischemia and stroke. Journal of Cerebral Blood Flow & Metabolism. 2021. PMID:33615874