GABBR1

Alpha-helical parts of the C-terminal intracellular region mediate heterodimeric interaction with GABBR2 (PubMed:9872744). The linker region between the transmembrane domain 3 (TM3) and the transmembrane domain 4 (TM4) probably plays a role in the specificity for G-protein coupling (PubMed:9844003).

Component of a heterodimeric G-protein coupled receptor for GABA, formed by GABBR1 and GABBR2 (PubMed:15617512, PubMed:18165688, PubMed:22660477, PubMed:24305054, PubMed:36103875, PubMed:9872316, PubMed:9872744). 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:10906333, PubMed:24305054, PubMed:9872744). Signaling inhibits adenylate cyclase, stimulates phospholipase A2, activates potassium channels, inactivates voltage-dependent calcium-channels and modulates inositol phospholipid hydrolysis (PubMed:10075644). Calcium is required for high affinity binding to GABA (By similarity). Plays a critical role in the fine-tuning of inhibitory synaptic transmission (PubMed:9844003). 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:10075644, PubMed:22660477, PubMed:9844003, PubMed:9872316, PubMed:9872744). Not only implicated in synaptic inhibition but also in hippocampal long-term potentiation, slow wave sleep, muscle relaxation and antinociception (Probable). Activated by (-)-baclofen, cgp27492 and blocked by phaclofen (PubMed:24305054, PubMed:9844003, PubMed:9872316).

Isoform 1E may regulate the formation of functional GABBR1/GABBR2 heterodimers by competing for GABBR2 binding. This could explain the observation that certain small molecule ligands exhibit differential affinity for central versus peripheral sites.

Neurodevelopmental disorder with language delay and variable cognitive abnormalities

NEDLC

An autosomal dominant disorder characterized by language delay ranging from mild to severe, varying degrees of intellectual disability, and learning difficulties. Additional features include early motor delay, muscular hypotonia, behavioral abnormalities, sleep disorders, and seizures.

None

The disease is caused by variants affecting the gene represented in this entry.

Belongs to the G-protein coupled receptor 3 family. GABA-B receptor subfamily.

Highly expressed in brain (PubMed:9753614, PubMed:9844003, PubMed:9872744). Weakly expressed in heart, small intestine and uterus. Isoform 1A: Mainly expressed in granular cell and molecular layer (PubMed:9844003). Isoform 1B: Mainly expressed in Purkinje cells (PubMed:9844003). Isoform 1E: Predominantly expressed in peripheral tissues as kidney, lung, trachea, colon, small intestine, stomach, bone marrow, thymus and mammary gland (PubMed:10906333).

• Cell membrane
• Multi-pass membrane protein
• Postsynaptic cell membrane
• Multi-pass membrane protein
• Cell projection
• Dendrite
• Colocalizes with ATF4 in hippocampal neuron dendritic membranes (By similarity). Coexpression of GABBR1 and GABBR2 is required for GABBR1 maturation and transport to the plasma membrane (PubMed:15617512).
• Isoform 1E
• Secreted

GPRC3A, GABBR1, Gamma-aminobutyric acid type B receptor subunit 1, GABA-B receptor 1, GABA-B-R1, GABA-BR1, GABABR1, Gb1

• entrezGene:2550
• omim:603540
• swissprot:Q9UBS5

Proteins

Neuroscience

108320Da