ADARB1 Protein (Adenosine Deaminase Acting on RNA 1)

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

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

Catalytic Mechanism

ADARB1 catalyzes A-to-I editing through a hydrolytic deamination reaction:

Adenosine + H₂O → Inosine + NH₃

The reaction mechanism involves:

Normal 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

Interaction Network

ADARB1 interacts with and is regulated by:

Therapeutic Targeting

Gene Therapy Approaches

ADARB1 modulators are being developed for:

Small 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