GABA<sub>A</sub> receptor β3 subunit | GABA<sub>A</sub> receptors | IUPHAR/BPS Guide to PHARMACOLOGY

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GABAA receptor β3 subunit

Target not currently curated in GtoImmuPdb

Target id: 412

Nomenclature: GABAA receptor β3 subunit

Family: GABAA receptors

Annotation status:  image of a green circle Annotated and expert reviewed. Please contact us if you can help with updates.  » Email us

Contents:

Gene and Protein Information
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human 4 473 15q11.2-q12 GABRB3 gamma-aminobutyric acid type A receptor beta3 subunit 6-7
Mouse 4 473 7 C Gabrb3 gamma-aminobutyric acid (GABA) A receptor, subunit beta 3 2
Rat 4 473 1q22 Gabrb3 gamma-aminobutyric acid type A receptor beta 3 subunit 4,8
Previous and Unofficial Names
gamma-aminobutyric acid receptor subunit beta-3 | Gabrb-3 | Cp1 | gamma-aminobutyric acid (GABA) A receptor, beta 3 | gamma-aminobutyric acid (GABA) A receptor, subunit beta 3 | gamma-aminobutyric acid (GABA) A receptor
Database Links
CATH/Gene3D 2.70.170.10
ChEMBL Target CHEMBL1847 (Hs), CHEMBL2094133 (Mm), CHEMBL1907607 (Rn)
DrugBank Target P28472 (Hs), P28472 (Hs)
Ensembl Gene ENSG00000166206 (Hs), ENSMUSG00000033676 (Mm), ENSRNOG00000014938 (Rn)
Entrez Gene 2562 (Hs), 14402 (Mm), 24922 (Rn)
Human Protein Atlas ENSG00000166206 (Hs)
KEGG Gene hsa:2562 (Hs), mmu:14402 (Mm), rno:24922 (Rn)
OMIM 137192 (Hs)
Orphanet ORPHA159621 (Hs)
RefSeq Nucleotide NM_000814 (Hs), NM_021912 (Hs), NM_008071 (Mm), NM_017065 (Rn)
RefSeq Protein NP_000805 (Hs), NP_068712 (Hs), NP_032097 (Mm), NP_058761 (Rn)
UniProtKB P28472 (Hs), P63080 (Mm), P63079 (Rn)
Wikipedia GABRB3 (Hs)
Selected 3D Structures
Image of receptor 3D structure from RCSB PDB
Description:  Crystal structure of a human gamma-aminobutyric acid receptor, the GABA(A)R-beta3 homopentamer
PDB Id:  4COF
Ligand:  benzamidine
Resolution:  2.97Å
Species:  Human
References:  5
Natural/Endogenous Ligands
GABA

Download all structure-activity data for this target as a CSV file

Channel Blockers
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Use-dependent Value Parameter Concentration range (M) Voltage-dependent (mV) Reference
picrotoxin Hs - no - - - no
⤷
Not voltage dependent
TBPS Hs - no - - - no
⤷
Not voltage dependent
Allosteric Modulators
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Concentration range (M) Voltage-dependent (mV) Reference
etazolate Hs Binding 5.5 pIC50 - no 9
⤷ pIC50 5.5 (IC50 3.5x10-6 M) [9]
Not voltage dependent
Description: inhibition of [35S]TBPS binding
Tissue Distribution
The β3 subunit is widely distributed in the brain. It is strongly expressed in the cerebral cortices, hippocampus, striatum, olfactory bulb, and parts of the hypothalamus and cerebellum (granule cell layer). In the hippocamus, β3 subunits are highly expressed in dendrites of principal cells. It is less strongly expressed in the pallidum and thalamic nuclei, and brain stem. There is a striking correspondence in the distribution of subunits α2 and β3. Both are strongly stained in the accessory olfactory bulb, striatum, septum, molecular layer of the dentate gyrus and the hypothalamus. Staining for both subunits is less intense in the thalamus and brainstem.
Species:  Rat
Technique:  Immunohistochemistry
References:  7
The distribution of the β3 subunit largely matches that of β1. Immunoreactivity of the β3 subunit, however, in general is stronger than that of β1. β3 immunoreactivity is most prominent in the molecular layer of the dentate gyrus and intense in the strata oriens and radiatum of CA1 and CA3. In CA2 considerably less β3 than β1 immunoreactivity was observed. The layers oif principal neurons and the terminal field of mossy fibres were spared for β1 and β3.
Species:  Rat
Technique:  Immunohistochemistry
References:  6
In situ hybridization signals for β3 subunits is strongest in the olfactory bulb, pyriform cortex, hippocampus, and the Purkinje cell and granule cell layer of the cerebellum. Signals are weaker in neocortex layer II/III, and V/VI, in caudate putamen and nucleus accumbens, bed nucleus of stria terminalis, medial habenula, hypothalamus. Signals are weak in thalamus, substantia nigra, and inferior colliculus and red nucleus.
Species:  Rat
Technique:  In situ hybridization
References:  8
Staining for the β3 subunit is considerably more concentrated in the striatum, nucleus accumbens, and olfactory tubercle than in the globus pallidus, entopeduncular nucleus, subthalamic nucleus.
Species:  Rat
Technique:  Immunohistochemistry
References:  4
In the spinal cord, labeling of motoneurons in layer IX is moderate for β3. Similarly, in layers II-VIII and X, the β3 transcripts were moderately expressed.
Species:  Rat
Technique:  In situ hybridization
References:  3
Thalamic nuclei and basal ganglia of Rhesus monkeys. The β3 subunit is variably expressed in practically all thalamic nuclei except for the lateral habenula. The overall expression pattern of the β3 subunit differs from that of β2. The β3 subunit was expressed in all basal ganglia nuclei displaying a unique pattern.
Species:  Rhesus macaque
Technique:  In situ hybridization
References: 
Clinically-Relevant Mutations and Pathophysiology
Disease:  Angelman syndrome
Disease Ontology: DOID:1932
OMIM: 105830
Role:  Deletion of the GABR3 gene due to maternal deficiency of chromosome 15q11-13 is associated with the pathogenesis of Angelman syndrome.
References:  7
Disease:  Autism
Synonyms: Autism spectrum disorder [Disease Ontology: DOID:0060041]
Disease Ontology: DOID:0060041
OMIM: 209850
Orphanet: ORPHA106
Disease:  Epilepsy, childhood absence, susceptibility to, 5; ECA5
Synonyms: Childhood absence epilepsy [Orphanet: ORPHA64280] [Disease Ontology: DOID:1825]
Disease Ontology: DOID:1825
OMIM: 612269
Orphanet: ORPHA64280
Disease:  Insomnia
References:  1
Disease:  Prader-Willi syndrome
Disease Ontology: DOID:11983
OMIM: 176270
Role:  Deletion of the GABR3 gene due to paternal deficiency of chromosome 15q11-13 is associated with the pathogenesis of Prader-Willi syndrome.
References:  7
Biologically Significant Variants
Type:  Splice variant
Species:  Human
Description:  This isoform is one of two that have the same amino acid length but which differ in their N-termini due to the inclusion of an alternative exon.
Amino acids:  473
Nucleotide accession:  NM_021912
Protein accession:  NP_068712
References:  3,6
Type:  Splice variant
Species:  Human
Description:  This isoform is one of two that have the same amino acid length but which differ in their N-termini due to the inclusion of an alternative exon.
Amino acids:  473
Nucleotide accession:  NM_000814
Protein accession:  NP_000805
References:  3,6

References

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1. Buhr A, Bianchi MT, Baur R, Courtet P, Pignay V, Boulenger JP, Gallati S, Hinkle DJ, Macdonald RL, Sigel E. (2002) Functional characterization of the new human GABA(A) receptor mutation beta3(R192H). Hum. Genet., 111 (2): 154-60. [PMID:12189488]

2. Ferguson C, Hardy SL, Werner DF, Hileman SM, Delorey TM, Homanics GE. (2007) New insight into the role of the beta3 subunit of the GABAA-R in development, behavior, body weight regulation, and anesthesia revealed by conditional gene knockout. BMC Neurosci, 8: 85. [PMID:17927825]

3. Kirkness EF, Fraser CM. (1993) A strong promoter element is located between alternative exons of a gene encoding the human gamma-aminobutyric acid-type A receptor beta 3 subunit (GABRB3). J. Biol. Chem., 268 (6): 4420-8. [PMID:8382702]

4. Lolait SJ, O'Carroll AM, Kusano K, Muller JM, Brownstein MJ, Mahan LC. (1989) Cloning and expression of a novel rat GABAA receptor. FEBS Lett., 246 (1-2): 145-8. [PMID:2540033]

5. Miller PS, Aricescu AR. (2014) Crystal structure of a human GABAA receptor. Nature, 512 (7514): 270-5. [PMID:24909990]

6. Wagstaff J, Chaillet JR, Lalande M. (1991) The GABAA receptor beta 3 subunit gene: characterization of a human cDNA from chromosome 15q11q13 and mapping to a region of conserved synteny on mouse chromosome 7. Genomics, 11 (4): 1071-8. [PMID:1664410]

7. Wagstaff J, Knoll JH, Fleming J, Kirkness EF, Martin-Gallardo A, Greenberg F, Graham JM, Menninger J, Ward D, Venter JC. (1991) Localization of the gene encoding the GABAA receptor beta 3 subunit to the Angelman/Prader-Willi region of human chromosome 15. Am. J. Hum. Genet., 49 (2): 330-7. [PMID:1714232]

8. Ymer S, Schofield PR, Draguhn A, Werner P, Köhler M, Seeburg PH. (1989) GABAA receptor beta subunit heterogeneity: functional expression of cloned cDNAs. EMBO J., 8 (6): 1665-70. [PMID:2548852]

9. Zezula J, Slany A, Sieghart W. (1996) Interaction of allosteric ligands with GABAA receptors containing one, two, or three different subunits. Eur. J. Pharmacol., 301 (1-3): 207-14. [PMID:8773466]

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