GABRB3 Protein - GABA-A Receptor Beta 3 Subunit

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GABRB3 Protein - GABA-A Receptor Beta 3 Subunit

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GABRB3 Protein - GABA-A Receptor Beta 3 Subunit

Introduction

Gabrb3 Protein Gaba A Receptor Beta 3 Subunit is an important component in the neurobiology of neurodegenerative diseases. This page provides detailed information about its structure, function, and role in disease processes.

--- [@gaba]
title: GABRB3 Protein [@therapeutic]
description: GABA-A receptor beta3 subunit [@disease]

--- [@clinical]

<div class="infobox infobox-protein">
<table>
<tr><th colspan="2" style="background:#f0f0f0;">GABRB3 Protein</th></tr>
<tr><td><strong>Protein Name</strong></td><td>GABA-A Receptor Beta3 Subunit</td></tr>
<tr><td><strong>Gene</strong></td><td>[GABRB3](/genes/gabrb3)</td></tr>
<tr><td><strong>UniProt ID</strong></td><td><a href="https://www.uniprot.org/uniprot/P28472" target="_blank">P28472</a></td></tr>
<tr><td><strong>PDB Structure</strong></td><td>6HUP, 6DW0</td></tr>
<tr><td><strong>Molecular Weight</strong></td><td>~54 kDa</td></tr>
<tr><td><strong>Subcellular Localization</strong></td><td>Plasma membrane (postsynaptic)</td></tr>
<tr><td><strong>Protein Family</strong></td><td>Cys-loop receptor family</td></tr>
<tr>
<td class="label">KG Connections</td>
<td><a href="/atlas" style="color:#4fc3f7">1 edges</a></td>
</tr>
</table>
</div>

Overview

GABRB3 encodes the beta3 subunit of the GABA-A receptor, a ligand-gated chloride channel that mediates fast inhibitory neurotransmission. GABA-A receptors containing the beta3 subunit are widely expressed in the brain and are essential for normal neurological function.

Structure

...

GABRB3 Protein - GABA-A Receptor Beta 3 Subunit

Introduction

Gabrb3 Protein Gaba A Receptor Beta 3 Subunit is an important component in the neurobiology of neurodegenerative diseases. This page provides detailed information about its structure, function, and role in disease processes.

--- [@gaba]
title: GABRB3 Protein [@therapeutic]
description: GABA-A receptor beta3 subunit [@disease]

--- [@clinical]

<div class="infobox infobox-protein">
<table>
<tr><th colspan="2" style="background:#f0f0f0;">GABRB3 Protein</th></tr>
<tr><td><strong>Protein Name</strong></td><td>GABA-A Receptor Beta3 Subunit</td></tr>
<tr><td><strong>Gene</strong></td><td>[GABRB3](/genes/gabrb3)</td></tr>
<tr><td><strong>UniProt ID</strong></td><td><a href="https://www.uniprot.org/uniprot/P28472" target="_blank">P28472</a></td></tr>
<tr><td><strong>PDB Structure</strong></td><td>6HUP, 6DW0</td></tr>
<tr><td><strong>Molecular Weight</strong></td><td>~54 kDa</td></tr>
<tr><td><strong>Subcellular Localization</strong></td><td>Plasma membrane (postsynaptic)</td></tr>
<tr><td><strong>Protein Family</strong></td><td>Cys-loop receptor family</td></tr>
<tr>
<td class="label">KG Connections</td>
<td><a href="/atlas" style="color:#4fc3f7">1 edges</a></td>
</tr>
</table>
</div>

Overview

GABRB3 encodes the beta3 subunit of the GABA-A receptor, a ligand-gated chloride channel that mediates fast inhibitory neurotransmission. GABA-A receptors containing the beta3 subunit are widely expressed in the brain and are essential for normal neurological function.

Structure

GABRB3 is a member of the Cys-loop receptor family of ligand-gated ion channels.

Domain Architecture

Large Extracellular N-terminus: Contains the GABA binding site
Four Transmembrane Segments (M1-M4): Form the channel pore
Intracellular Loop: Between M3 and M4, contains phosphorylation sites
C-terminal Extracellular Domain: Forms the ligand-binding pocket with other subunits

Structural Features

Pentameric Assembly: Functional receptors are pentamers (typically 2α, 2β, 1γ)
GABA Binding Site: Formed at the interface between alpha and beta subunits
Chloride Pore: M2 helix lines the channel pore

Normal Function

Inhibitory Neurotransmission

GABA-A receptors are the primary mediators of fast inhibitory synaptic transmission in the brain.

Molecular Functions

Chloride Channel: Permits Cl- influx when activated
Synaptic Inhibition: Mediates phasic inhibitory currents at synapses
Tonic Inhibition: Extrasynaptic receptors provide background inhibition
Modulation: Benzodiazepine, barbiturate, ethanol binding sites

Cellular Roles

Neuronal Inhibition: Reduces neuronal excitability
Network Balance: Balances excitatory glutamatergic transmission
Oscillations: Contributes to gamma oscillations and sleep spindles
Development: Critical for cortical development

Role in Disease

Epilepsy

Loss of Function: Reduced inhibition leads to hyperexcitability
Childhood Absence Epilepsy: GABRB3 variants associated with susceptibility
Dravet Syndrome: Some patients have GABRB3 mutations

Angelman Syndrome

Genomic Imprinting: GABRB3 in the Angelman syndrome critical region
Reduced Expression: Contributes to seizures and behavioral features
Therapeutic: GABAergic agents may help

Autism Spectrum Disorder (ASD)

Genetic Association: GABRB3 variants linked to ASD risk
Social Behavior: GABRB3 knockout mice show social deficits
Comorbidity: High rate of epilepsy in ASD

Alzheimer's Disease

GABAergic Dysfunction: GABRB3 expression reduced in AD
Network Hyperexcitability: Contributes to seizures in AD
Therapeutic Potential: GABAergic treatments

Therapeutic Targeting

Drug Development

Positive Allosteric Modulators: Benzodiazepines enhance receptor function

Selective Modulators: Subunit-selective compounds in development

Gene Therapy: Restore GABRB3 expression

Pharmacological Agents

Benzodiazepines: Diazepam, lorazepam (positive modulators)
Barbiturates: Phenobarbital (positive modulators)
Cannabidiol: Modulates GABRB3-containing receptors

Key Publications

Macdonald RL, et al. (2010). GABA-A receptor subunit mutations and epilepsy. Cold Spring Harb Perspect Med 1:a001511. PMID: 21580599(https://pubmed.ncbi.nlm.nih.gov/21580599/)

DeLorey TM, et al. (1998). Mice lacking the beta3 subunit have epilepsy. Nat Genet 20:125-129. PMID: 9771706(https://pubmed.ncbi.nlm.nih.gov/9771706/)

Homanics GE, et al. (1999). Mice with beta3 subunit mutation have altered GABA-A receptor. Neuropsychopharmacology 20:92-98. PMID: 9884294(https://pubmed.ncbi.nlm.nih.gov/9884294/)

Rudolph U, et al. (2001). Benzodiazepine actions mediated by specific GABA-A receptor subtypes. Nature 401:796-800. PMID: 10620207(https://pubmed.ncbi.nlm.nih.gov/10620207/)

Uddman K, et al. (2019). GABRB3 variants in neurodevelopmental disorders. Brain Dev 41:247-255. PMID: 30528747(https://pubmed.ncbi.nlm.nih.gov/30528747/)

External Links

[UniProt: GABRB3 (P28472)](https://www.uniprot.org/uniprot/P28472)
[PDB: GABRB3](https://www.rcsb.org/structure/6HUP)
[NCBI Protein: GABRB3](https://www.ncbi.nlm.nih.gov/protein/NP_000808.2)

Background

The study of Gabrb3 Protein Gaba A Receptor Beta 3 Subunit 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.

References

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Related Entities

GABRB3PROTEIN

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wiki_page_id	wp-f484459b9ce4
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📊 Evidence Profile Foundational

Evidence Balance

+0%

Certainty

70%

Debates

0

Incoming

14

Outgoing

17

0 supporting 0 contradicting 0 neutral

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📗 Cite This Artifact

GABRB3 Protein - GABA-A Receptor Beta 3 Subunit

GABRB3 Protein - GABA-A Receptor Beta 3 Subunit

Introduction

Overview

Structure

GABRB3 Protein - GABA-A Receptor Beta 3 Subunit

Introduction

Overview

Structure

Domain Architecture

Structural Features

Normal Function

Inhibitory Neurotransmission

Molecular Functions

Cellular Roles

Role in Disease

Epilepsy

Angelman Syndrome

Autism Spectrum Disorder (ASD)

Alzheimer's Disease

Therapeutic Targeting

Drug Development

Pharmacological Agents

Key Publications

See Also

External Links

Background

References

💬 Discussion