Molecular Target Synopsis
Overview
Domains and Structures
Drugs and Clinical Candidates
Druggability
Chemistry
Ligand Efficiency Plot
Pathways
Family Cladogram
Interaction Network
Gene Expression
Gene Copy Number Variation
RNAi
Mutations
Germline Genetics

GABRB3 (P28472) - Overview - Molecular Target Synopsis

Protein


GABRB3, Gamma-aminobutyric acid receptor subunit beta-3
UniProt P28472

Also Known as GBRB3_HUMAN, GABRB3

Ligand-gated chloride channel which is a component of the heteropentameric receptor for GABA, the major inhibitory neurotransmitter in the brain (PubMed:18514161, PubMed:22303015, PubMed:26950270, PubMed:22243422, PubMed:24909990). Plays an important role in the formation of functional inhibitory GABAergic synapses in addition to mediating synaptic inhibition as a GABA-gated ion channel (PubMed:25489750). The gamma2 subunit is necessary but not sufficient for a rapid formation of active synaptic contacts and the synaptogenic effect of this subunit is influenced by the type of alpha and beta subunits present in the receptor pentamer (By similarity). The alpha1/beta3/gamma2 receptor exhibits synaptogenic activity (PubMed:25489750). The alpha2/beta3/gamma2 receptor shows very little or no synaptogenic activity (By similarity). Functions also as histamine receptor and mediates cellular responses to histamine (PubMed:18281286). Plays an important role in somatosensation and in the production of antinociception (By similarity). Heteropentamer, formed by a combination of alpha, beta, gamma, delta and rho chains (PubMed:22243422, PubMed:18281286, PubMed:18514161, PubMed:24909990). Can form functional homopentamers (in vitro) (PubMed:22303015). Interacts with UBQLN1 (By similarity). May interact with KIF21B (By similarity). Identified in a complex of 720 kDa composed of LHFPL4, NLGN2, GABRA1, GABRB2, GABRG2 and GABRB3 (By similarity). Interacts with LHFPL4 (By similarity).

6HUJ
CRYOEM STRUCTURE OF HUMAN FULL-LENGTH HETEROMERIC ALPHA1BETA3GAMMA2L GABA(A)R IN COMPLEX WITH PICROTOXIN, GABA AND MEGABODY MB38.
RCSB/PDB
Inspect Structure
See all 3D Structures for GABRB3

Isoforms / Transcripts (Protein Coding)


Drugs


GABRB3 is targeted by Approved Drugs Eszopiclone, Etomidate, Ethchlorvynol, Methohexital, Clobazam. (see details)
Eszopiclone
Etomidate
Ethchlorvynol
Methohexital
Clobazam

Sub-cellular localization


UniProt: GABRB3 is active in the following subcellular-locations: cell junction, cell membrane, cytoplasmic vesicle membrane, postsynaptic cell membrane, synapse.
GO terms: GABRB3 is active in the following subcellular-locations: cell junction, chloride channel complex, cytoplasmic vesicle membrane, GABA-A receptor complex, GABA-ergic synapse, integral component of plasma membrane, neuron projection, plasma membrane, postsynaptic membrane, synapse.



UniProt
GO terms

Gene Copy Number Variation


In COSMIC - Cell Lines Project GABRB3 has gain in 1 cell-lines, loss in 1 cell-lines and no signal in 1003 cell-lines. (see details)

Gene Expression


In NCI60, the highest expressing cell lines are: A549, UACC_257, A498

In Array Express (RNA-seq of 675 commonly used human cancer cell lines), the highest expressing cell lines are: NCI-H209, SK-N-FI, HCC12

In Array Express (RNA-seq of long poly adenylated RNA and long non poly adenylated RNA from ENCODE cell lines), the highest expressing cell lines are: A549, SK-N-SH, NHLF

(see details)

3D Structures


For GABRB3 there are:
10 structures (31 chains) solved
10 are solved in complex with at least one small molecule ligand
1 are solved with an approved drug

GABRB3 is solved in complex with the approved drug(s):

DZP/DIAZEPAM (6HUP_B, 6HUP_E).

(see details)
Molecular Target 3D Synopsis

Screening and Chemistry


GABRB3 has been screened with 1670 compounds (6137 bioactivities), 1087 compounds have bioactivities that show binding affinity of <= 500nM (3198 bioactivities). (see details)