Adar 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.
Overview
<div class="infobox infobox-protein"> [@nishikura2016] | Property | Value | [@george2021] |----------|-------| [@hogg2011] | Protein Name | ADAR (RNA-specific adenosine deaminase) | [@samuel2019] | Gene | ADAR | | UniProt ID | P55265 | | PDB ID | 5HPJ, 6AKM | | Molecular Weight | ~122 kDa | | Subcellular Localization | Nucleus, Cytoplasm | | Protein Family | Adenosine deaminase family | | Aliases | ADAR1, A-to-I editing enzyme, dsRNA-specific adenosine deaminase | </div>
Structure
The ADAR protein contains multiple functional domains:
N-terminal dsRNA binding domains (dsRBDs): Three dsRBDs (dsRBD1, dsRBD2, dsRBD3) that recognize and bind to double-stranded RNA
Z-DNA binding domain (Zα): Binds to left-handed Z-DNA structures
Deaminase domain: The catalytic domain that performs adenosine deamination
The catalytic deaminase domain belongs to the metalloenzyme superfamily and requires zinc ions for catalytic activity. The protein can form homodimers, which is important for its enzymatic function.
Normal Function
ADAR (adenosine deaminase acting on RNA) is a dsRNA-specific adenosine deaminase that catalyzes the hydrolytic deamination of adenosine to inosine (A-to-I editing) in RNA molecules. This is the most prevalent form of RNA editing in mammals.
Key Functions
...
ADAR Protein
Introduction
Adar 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.
Overview
<div class="infobox infobox-protein"> [@nishikura2016] | Property | Value | [@george2021] |----------|-------| [@hogg2011] | Protein Name | ADAR (RNA-specific adenosine deaminase) | [@samuel2019] | Gene | ADAR | | UniProt ID | P55265 | | PDB ID | 5HPJ, 6AKM | | Molecular Weight | ~122 kDa | | Subcellular Localization | Nucleus, Cytoplasm | | Protein Family | Adenosine deaminase family | | Aliases | ADAR1, A-to-I editing enzyme, dsRNA-specific adenosine deaminase | </div>
Structure
The ADAR protein contains multiple functional domains:
N-terminal dsRNA binding domains (dsRBDs): Three dsRBDs (dsRBD1, dsRBD2, dsRBD3) that recognize and bind to double-stranded RNA
Z-DNA binding domain (Zα): Binds to left-handed Z-DNA structures
Deaminase domain: The catalytic domain that performs adenosine deamination
The catalytic deaminase domain belongs to the metalloenzyme superfamily and requires zinc ions for catalytic activity. The protein can form homodimers, which is important for its enzymatic function.
Normal Function
ADAR (adenosine deaminase acting on RNA) is a dsRNA-specific adenosine deaminase that catalyzes the hydrolytic deamination of adenosine to inosine (A-to-I editing) in RNA molecules. This is the most prevalent form of RNA editing in mammals.
Key Functions
A-to-I editing: Catalyzes the conversion of adenosine to inosine in double-stranded RNA regions
RNA splicing regulation: Editing within intronic regions can alter splice site selection
MiRNA biogenesis: Editing of pri-miRNA and pre-miRNA affects processing by Dicer
Innate immunity: Editing of self-RNA prevents inappropriate activation of MDA5-mediated interferon responses
Epigenetic regulation: Inosine-containing RNAs can influence chromatin remodeling
Substrate Specificity
ADAR preferentially edits:
Long dsRNA regions (>40 bp)
Stem-loop structures in pre-mRNAs and miRNA precursors
Non-coding RNAs including Alu repeats in human transcripts
Role in Neurodegeneration
Alzheimer's Disease
GRIA2 editing: ADAR-mediated editing of the GRIA2 (GluA2) AMPA receptor subunit is reduced in AD brain, leading to increased Ca²⁺ influx through unedited channels
RNA metabolism: Global reduction in A-to-I editing in AD temporal [cortex](/brain-regions/cortex)
[Tau](/proteins/tau) pathology: [Tau](/proteins/tau) accumulation may affect ADAR localization and activity
Amyotrophic Lateral Sclerosis
Excitotoxicity: Reduced GRIA2 editing in ALS motor [neurons](/entities/neurons) contributes to excitotoxic cell death
RNA granules: ADAR activity is affected by stress granule dynamics in ALS
SOD1 editing: Potential editing of SOD1 transcripts may influence aggregation
Other Neurodegenerative Conditions
Huntington's disease: Altered editing patterns in HD striatum
Epilepsy: ADAR2 activity is dysregulated in epileptic tissue
Aicardi-Goutières syndrome: Loss-of-function mutations cause autoimmune encephalopathy
Therapeutic Targeting
| Approach | Status | Description | |----------|--------|-------------| | Small molecule activators | Preclinical | Compounds that enhance ADAR activity | | RNA-based therapies | Research | siRNA to modulate ADAR expression | | Gene therapy | Research | AAV-mediated delivery of ADAR | | Editing reporters | Diagnostic | Measuring ADAR activity as biomarker |
Key Publications
<sup>[1]</sup> Slot, L.M. et al. (2020). Altered A-to-I RNA editing in [Alzheimer's disease](/diseases/alzheimers-disease). Nat Neurosci 23, 1287-1293.
<sup>[2]</sup> Hideyama, T. et al. (2010). Profound loss of GRIA2 editing in amyotrophic lateral sclerosis. J Neurosci 30, 16042-16051.
<sup>[3]</sup> Orlandi, C. et al. (2021). ADAR-mediated RNA editing in neurodegenerative diseases. Prog Neurobiol 205, 101984.
<sup>[4]</sup> Goodman, R.H. & Im, H. (2019). ADAR-mediated RNA editing in brain. Neuron 101, 10-14.
Background
The study of Adar 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.