GABBR2

The multi-pass membrane protein encoded by this gene belongs to the G-protein coupled receptor 3 family and GABA-B receptor subfamily. The GABA-B receptors inhibit neuronal activity through G protein-coupled second-messenger systems, which regulate the release of neurotransmitters, and the activity of ion channels and adenylyl cyclase. This receptor subunit forms an active heterodimeric complex with GABA-B receptor subunit 1, neither of which is effective on its own. Allelic variants of this gene have been associated with nicotine dependence.[provided by RefSeq, Jan 2010]

Gamma-Aminobutyric Acid Type B Receptor Subunit 2

Component of a heterodimeric G-protein coupled receptor for GABA, formed by GABBR1 and GABBR2 (PubMed:9872316, PubMed:9872744, PubMed:15617512, PubMed:18165688, PubMed:22660477, PubMed:24305054).

Within the heterodimeric GABA receptor, only GABBR1 seems to bind agonists, while GABBR2 mediates coupling to G proteins (PubMed:18165688).

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 (PubMed:10075644, PubMed:10773016, PubMed:24305054).

Signaling inhibits adenylate cyclase, stimulates phospholipase A2, activates potassium channels, inactivates voltage-dependent calcium-channels and modulates inositol phospholipid hydrolysis (PubMed:10075644, PubMed:9872744, PubMed:10906333, PubMed:10773016).

Plays a critical role in the fine-tuning of inhibitory synaptic transmission (PubMed:9872744, PubMed:22660477).

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 (PubMed:9872316, PubMed:10075644, PubMed:9872744, PubMed:22660477).

Not only implicated in synaptic inhibition but also in hippocampal long-term potentiation, slow wave sleep, muscle relaxation and antinociception (Probable).

Chemical synaptic transmission Source: ProtInc
Gamma-aminobutyric acid signaling pathway Source: UniProtKB
G protein-coupled receptor signaling pathway Source: ProtInc
Negative regulation of adenylate cyclase activity Source: ProtInc
Neuron-glial cell signaling Source: ARUK-UCL

Cell membrane; Postsynaptic cell membrane. Coexpression of GABBR1 and GABBR2 is required for GABBR1 maturation and transport to the plasma membrane. In contrast, GABBR2 does not depend on GABBR1 for transport to the cell membrane.

Neurodevelopmental disorder with poor language and loss of hand skills (NDPLHS):
An autosomal dominant disorder characterized by psychomotor developmental stagnation or regression. NDPLHS manifest in the first years of life as loss of purposeful hand movements, loss of language, and intellectual disability.
Developmental and epileptic encephalopathy 59 (DEE59):
A form of epileptic encephalopathy, a heterogeneous group of severe early-onset epilepsies characterized by refractory seizures, neurodevelopmental impairment, and poor prognosis. Development is normal prior to seizure onset, after which cognitive and motor delays become apparent. DEE59 is an autosomal dominant condition characterized by onset of refractory seizures in early infancy.

Extracellular: 42-483
Helical: 484-504
Cytoplasmic: 505-522
Helical: 523-543
Extracellular: 544-551
Helical: 552-572
Cytoplasmic: 573-597
Helical: 598-618
Extracellular: 619-654
Helical: 655-675
Cytoplasmic: 676-691
Helical: 692-712
Extracellular: 713-720
Helical: 721-741
Cytoplasmic: 742-941