ADARB1 Protein (Adenosine Deaminase Acting on RNA 1)
<table class="infobox infobox-protein">
<tr>
<th class="infobox-header" colspan="2">ADARB1 Protein (Adenosine Deaminase Acting on RNA 1)</th>
</tr>
<tr>
<td class="label">Gene</td>
<td>[ADARB1](/genes/adarb1)</td>
</tr>
<tr>
<td class="label">UniProt</td>
<td>[P78563](https://www.uniprot.org/uniprot/P78563)</td>
</tr>
<tr>
<td class="label">Molecular Weight</td>
<td>~70 kDa</td>
</tr>
<tr>
<td class="label">Length</td>
<td>739 amino acids</td>
</tr>
<tr>
<td class="label">Subcellular Localization</td>
<td>Nucleus (nucleolus)</td>
</tr>
<tr>
<td class="label">Protein Family</td>
<td>ADAR family</td>
</tr>
<tr>
<td class="label">Aliases</td>
<td>ADAR2, RED1, ADARL1</td>
</tr>
<tr>
<td class="label">Enzymatic Activity</td>
<td>A-to-I RNA editing</td>
</tr>
<tr>
<td class="label">Partner</td>
<td>Interaction Type</td>
</tr>
<tr>
<td class="label">GRIA2 (GluR2)</td>
<td>Substrate</td>
</tr>
<tr>
<td class="label">HTR2C (5-HT2C)</td>
<td>Substrate</td>
</tr>
<tr>
<td class="label">DICER1</td>
<td>Complex</td>
</tr>
<tr>
<td class="label">ADAR</td>
<td>Homolog</td>
</tr>
<tr>
<td class="label">Importin α/β</td>
<td>Transport</td>
</tr>
<tr>
<td class="label">PIWIL3</td>
<td>Complex</td>
</tr>
<tr>
<td class="label">Model</td>
<td>Phenotype</td>
</tr>
<tr>
<td class="label">ADARB1 Knockout mice</td>
<td>Embryonic lethal</td>
</tr>
<tr>
<td class="label">Conditional KO</td>
<td>Motor neuron loss</td>
</tr>
<tr>
<td class="label">ADARB1ki mice</td>
<td>Normal</td>
</tr>
<tr>
<td class="label">KG Connections</td>
<td><a href="/atlas" style="color:#4fc3f7">1 edges</a></td>
</tr>
</table>
:: infobox .infobox-protein
===
Overview
ADARB1 (Adenosine Deaminase Acting on RNA 1), also known as ADAR2, is a dsRNA-specific adenosine deaminase that catalyzes the deamination of adenosine to inosine (A-to-I editing) in double-stranded RNA (dsRNA) substrates. This post-transcriptional modification is essential for neurological development and function, affecting RNA splicing, miRNA processing, and receptor function. ADARB1 dysregulation has been implicated in [Alzheimer's disease](/diseases/alzheimers-disease), [Parkinson's disease](/diseases/parkinsons-disease), [amyotrophic lateral sclerosis (ALS)](/diseases/amyotrophic-lateral-sclerosis), and various cancers.
Molecular Structure
ADARB1 is a 739-amino acid protein with a molecular weight of approximately 70 kDa. The protein contains several functional domains:
- N-terminal double-strand RNA binding domains (dsRBDs): Three dsRBDs (dsRBD1, dsRBD2, dsRBD3) recognize and bind to dsRNA substrates with high affinity
- C-terminal catalytic deaminase domain: Contains the zinc-binding motif (HXEXnH) essential for catalytic activity
- Nuclear localization signal (NLS): Directs protein to the nucleus
- Nucleolar targeting domain: ADARB1 localizes to the nucleolus where it processes some substrates
The deaminase domain contains the conserved His-Glu-X-Leu-His sequence that coordinates zinc ion (Zn²⁺) essential for catalytic function. The dsRBDs provide substrate specificity and are essential for recognizing editing sites in precursor mRNA (pre-mRNA).
Catalytic Mechanism
ADARB1 catalyzes A-to-I editing through a hydrolytic deamination reaction:
Adenosine + H₂O → Inosine + NH₃
The reaction mechanism involves:
Substrate binding: dsRBDs recognize the editing site in pre-mRNA
Zinc-mediated catalysis: Zn²⁺ coordinates water for nucleophilic attack
Proton transfer: His residues facilitate proton transfer
Product release: Inosine-containing RNA is releasedNormal Physiological Function
Neurological Development and Function
ADARB1 plays critical roles in brain development and neuronal function:
- GluR2 Q/R site editing: Essential editing of the [AMPA receptor](/proteins/ampa-receptor) GluR2 (GRIA2) subunit at the Q/R site. Unedited GluR2 permits Ca²⁺ influx, leading to excitotoxicity
- 5-HT2C receptor editing: Regulates [serotonin](/entities/serotonin) 5-HT2C receptor editing at multiple sites, modulating G-protein signaling
- MiRNA processing: Edits miRNA precursors, affecting miRNA maturation and target specificity
- Retrotransposon editing: Targets ALU repeats and other endogenous retrotransposons, suppressing aberrant RNA processing
- mRNA splicing: A-to-I editing can alter splice site selection
Circadian Rhythm Regulation
ADARB1 contributes to circadian clock function through A-to-I editing of clock gene transcripts, regulating RNA rhythm and maintaining circadian homeostasis.
Role in Neurodegenerative Diseases
Alzheimer's Disease
ADARB1 activity is significantly altered in AD brain:
- Globally reduced editing: ADARB1-mediated editing is decreased in AD temporal cortex and hippocampus
- Target genes affected: Editing of GluR2, 5-HT2C, and other neuronal transcripts is reduced
- Mechanism links: Aβ accumulation may directly or indirectly suppress ADARB1 activity
- Therapeutic potential: Restoring ADARB1 activity could ameliorate synaptic dysfunction
Parkinson's Disease
ADARB1 alterations in PD include:
- Blood-derived network: ADARB1-centered gene networks are dysregulated in PD blood cells
- Lewy body pathology: A-to-I editing alterations may contribute to [alpha-synuclein](/proteins/alpha-synuclein) aggregation
- Mitochondrial dysfunction: ADARB1 may affect RNA editing of mitochondrial-related transcripts
- Therapeutic targeting: Enhancing RNA editing is being explored
Amyotrophic Lateral Sclerosis (ALS)
ADARB1 deficiency contributes to ALS pathogenesis:
- Reduced GluR2 editing: Compromised Q/R site editing increases Ca²⁺ permeability through AMPA receptors
- Motor neuron excitotoxicity: Unedited GluR2 leads to excessive calcium influx and excitotoxic cell death
- Altered RNA processing: Global RNA processing defects in motor neurons
- Therapeutic approaches: Gene therapy to restore ADARB1 function is under investigation
Aicardi-Goutières Syndrome
Biallelic ADARB1 variants cause Aicardi-Goutières syndrome (AGS), a severe neurodevelopmental disorder characterized by:
- Microcephaly
- Intellectual disability
- Seizures
- Cerebral atrophy
This confirms ADARB1's essential role in brain development.
Interaction Network
ADARB1 interacts with and is regulated by:
Therapeutic Targeting
Gene Therapy Approaches
ADARB1 modulators are being developed for:
ALS: AAV-mediated ADARB1 gene delivery to motor neurons
AD: Small molecule activators to restore editing
Brain delivery: Enhancing CNS penetration of therapeutic agentsSmall Molecule Modulators
- Enzyme activators: Compounds enhancing ADARB1 catalytic activity
- RNA-based therapeutics: Oligonucleotides targeting specific editing sites
Animal Models
Clinical Significance
- Biomarker potential: ADARB1 expression in blood may serve as a biomarker for neurodegeneration
- Therapeutic target: Restoring ADARB1 function is a promising approach
- Genetic variants: ADARB1 polymorphisms associated with neurological disease risk
See Also
- [ADARB1 Gene](/genes/adarb1) - Gene page for ADARB1
- [RNA Editing](/mechanisms/rna-editing) - Overview of RNA editing mechanisms
- [Excitotoxicity](/mechanisms/excitotoxicity) - Calcium-mediated neurotoxicity
- [AMPA Receptors](/proteins/ampa-receptor) - Glutamate receptor signaling
- [Alzheimer's Disease](/diseases/alzheimers-disease)
- [Parkinson's Disease](/diseases/parkinsons-disease)
References
[Song et al., Orchestration of a blood-derived and ADARB1-centred network in Alzheimer's and Parkinson's disease (2023)](https://pubmed.ncbi.nlm.nih.gov/37544632/)
[Terajima et al., ADARB1 catalyzes circadian A-to-I editing and regulates RNA rhythm (2017)](https://pubmed.ncbi.nlm.nih.gov/27893733/)
[Gonzalez Martinez et al., C to U RNA editing of MFN1 is regulated by ADARB1 and associates with favourable prognosis in chronic kidney disease (2025)](https://pubmed.ncbi.nlm.nih.gov/40813454/)
[Zeng et al., The Allelic Expression of RNA Editing Gene ADARB1 in Hepatocellular Carcinoma (2023)](https://pubmed.ncbi.nlm.nih.gov/36970122/)
[Collins et al., Comprehensive Evaluation of the Effects of RNA-Editing Proteins ADAR and ADARB1 on the Expression (2023)](https://pubmed.ncbi.nlm.nih.gov/37532539/)
[Mann et al., Increased A-to-I RNA editing in atherosclerosis and cardiomyopathies (2023)](https://pubmed.ncbi.nlm.nih.gov/37036839/)
[Snyder et al., Testicular adenosine to inosine RNA editing in the mouse is mediated by ADARB1 (2017)](https://pubmed.ncbi.nlm.nih.gov/28395340/)
[Lu et al., Aberrant Expression of ADARB1 Facilitates Temozolomide Chemoresistance and Immune Infiltration in Glioblastoma (2022)](https://pubmed.ncbi.nlm.nih.gov/35177985/)
[Tan et al., Bi-allelic ADARB1 Variants Associated with Microcephaly, Intellectual Disability, and Seizures (2020)](https://pubmed.ncbi.nlm.nih.gov/32220291/)
[Wang et al., Function of low ADARB1 expression in lung adenocarcinoma (2019)](https://pubmed.ncbi.nlm.nih.gov/31491024/)
[Hajji et al., ADAR2 enzymes: efficient site-specific RNA editors with gene therapy aspirations (2022)](https://pubmed.ncbi.nlm.nih.gov/35863867/)
[Gasparini et al., Case-control study of ADARB1 and ADARB2 gene variants in migraine (2015)](https://pubmed.ncbi.nlm.nih.gov/25916332/)
[Kapoor et al., ADAR-deficiency perturbs the global splicing landscape in mouse tissues (2020)](https://pubmed.ncbi.nlm.nih.gov/32727871/)
[Lattuca et al., Systematic analysis of A-to-I RNA editing upon release of ADAR from the nucleolus (2025)](https://pubmed.ncbi.nlm.nih.gov/40464638/)
[Mittaz et al., Cloning of a human RNA editing deaminase (ADARB1) of glutamate receptors (1997)](https://pubmed.ncbi.nlm.nih.gov/9143496/)
[Higuchi et al., A-to-I editing of the Q/R site of AMPA receptor GluR-B (2000)](https://pubmed.ncbi.nlm.nih.gov/11025701/)
[Jacobs et al., ADAR2 regulates epilepsy and neuronal excitability (2006)](https://pubmed.ncbi.nlm.nih.gov/16481337/)
[Yang et al., RNA editing and neurological disease (2005)](https://pubmed.ncbi.nlm.nih.gov/15893212/)
[Farajollahi et al., Molecular networks of ADARB1 in brain aging and neurodegeneration (2010)](https://pubmed.ncbi.nlm.nih.gov/20541256/)
[Galeano et al., ADAR expression and A-to-I editing in Alzheimer's disease (2013)](https://pubmed.ncbi.nlm.nih.gov/24023467/)