Gamma-aminobutyric acid type B receptor subunit 2

UniProt O75899 Organism Homo sapiens Gene GABBR2, GPR51, GPRC3B

Also known as: GABBR2, GPR51, GPRC3B

Function

Component of a heterodimeric G protein-coupled receptor for GABA, formed by GABBR1 and GABBR2. Within the heterodimeric GABA receptor, only GABBR1 seems to bind agonists, while GABBR2 mediates coupling to G proteins. Ligand binding causes a conformation change that triggers signaling via guanine nucleotide-binding proteins (G proteins) and modulates the activity of down-stream effectors, such as adenylate cyclase. Signaling inhibits adenylate cyclase, stimulates phospholipase A2, activates potassium channels, inactivates voltage-dependent calcium-channels and modulates inositol phospholipid hydrolysis. Plays a critical role in the fine-tuning of inhibitory synaptic transmission. Pre-synaptic GABA receptor inhibits neurotransmitter release by down-regulating high-voltage activated calcium channels, whereas postsynaptic GABA receptor decreases neuronal excitability by activating a prominent inwardly rectifying potassium (Kir) conductance that underlies the late inhibitory postsynaptic potentials. Not only implicated in synaptic inhibition but also in hippocampal long-term potentiation, slow wave sleep, muscle relaxation and antinociception (Probable).

Classification

Family (Pfam): PF00003 7tm_3, PF01094 ANF_receptor, PF18455 GBR2_CC
InterPro: ANF_lig-bd_rcpt, GBR2_CC, GPCR3_GABA-B, GPCR_3, GPCR_3_C, GPCR_3_CS, GPCR_3_GABA_rcpt_B2, Peripla_BP_I
Functional cluster: Cytochrome P450 & Heme Enzymes

Experimental structures · PDB · 26

4F11 X-ray 2.38A
4F12 X-ray 3.02A
4MQE X-ray 2.35A
4MQF X-ray 2.22A
4MR7 X-ray 2.15A
4MR8 X-ray 2.15A
4MR9 X-ray 2.35A
4MRM X-ray 2.86A
4MS1 X-ray 2.25A
4MS3 X-ray 2.50A
4MS4 X-ray 1.90A
4PAS X-ray 1.62A
… and 14 more

A predicted model is available from AlphaFold.

Gene Ontology · 16

Disease associations

neurodevelopmental disorder with poor language and loss of hand skills MONDO:0060659
developmental and epileptic encephalopathy, 59 MONDO:0033368

Drugs targeting this protein · 9

SGS-742 antagonist
SODIUM OXYBATE agonist
ARBACLOFEN PLACARBIL agonist
ARBACLOFEN agonist
LESOGABERAN agonist
CALCIUM OXYBATE agonist
MAGNESIUM OXYBATE agonist
POTASSIUM OXYBATE agonist
BACLOFEN agonist

Related proteins · sequence + function similarity

Co-cited proteins · studied together in the literature

Gamma-aminobutyric acid type B receptor subunit 1 9 shared papers
Gamma-aminobutyric acid type B receptor subunit 1 3 shared papers
Gamma-aminobutyric acid type B receptor subunit 1 3 shared papers
Gamma-aminobutyric acid type B receptor subunit 2 3 shared papers
Gamma-aminobutyric acid type B receptor subunit 2 1 shared papers
Gamma-aminobutyric acid receptor subunit beta-2 1 shared papers
BDNF/NT-3 growth factors receptor 1 shared papers
Dehydrodolichyl diphosphate synthase complex subunit DHDDS 1 shared papers
Dehydrodolichyl diphosphate synthase complex subunit NUS1 1 shared papers
Clathrin heavy chain 1 1 shared papers
Zinc finger and BTB domain-containing protein 18 1 shared papers
Rho-related BTB domain-containing protein 2 1 shared papers

Literature · 18 cited papers

A novel mutation in the transmembrane 6 domain of GABBR2 leads to a Rett-like phenotype. Ann. Neurol. · 2018
High rate of recurrent de novo mutations in developmental and epileptic encephalopathies. Am. J. Hum. Genet. · 2017
GABBR2 mutations determine phenotype in rett syndrome and epileptic encephalopathy. Ann. Neurol. · 2017
Identification of novel genetic causes of Rett syndrome-like phenotypes. J. Med. Genet. · 2016
Structural mechanism of ligand activation in human GABA(B) receptor. Nature · 2013
Structure and functional interaction of the extracellular domain of human GABA(B) receptor GBR2. Nat. Neurosci. · 2012
Direct detection of the interaction between recombinant soluble extracellular regions in the heterodimeric metabotropic gamma-aminobutyric acid receptor. J. Biol. Chem. · 2008
Subcellular distribution of GABA(B) receptor homo- and hetero-dimers. Biochem. J. · 2005
The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. · 2004
DNA sequence and analysis of human chromosome 9. Nature · 2004
Characterization of gamma-aminobutyric acid receptor GABAB(1e), a GABAB(1) splice variant encoding a truncated receptor. J. Biol. Chem. · 2000
Coexpression of full-length gamma-aminobutyric acid(B) (GABA(B)) receptors with truncated receptors and metabotropic glutamate receptor 4 supports the GABA(B) heterodimer as the functional receptor. J. Pharmacol. Exp. Ther. · 2000
… and 6 more in the literature graph

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