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MGP001128

UniProt Annotations

Entry Information
Gene Namegamma-aminobutyric acid (GABA) B receptor, 1
Protein EntryGABR1_HUMAN
UniProt IDQ9UBS5
SpeciesHuman
Comments
Comment typeDescription
Alternative ProductsEvent=Alternative splicing; Named isoforms=5; Comment=Isoforms corresponding to the full receptor are essentially found in the central nervous system (CNS).; Name=1A; IsoId=Q9UBS5-1; Sequence=Displayed; Name=1B; IsoId=Q9UBS5-2; Sequence=VSP_002037; Name=1C; IsoId=Q9UBS5-3; Sequence=VSP_002038; Name=1D; IsoId=Q9UBS5-4; Sequence=VSP_002040; Name=1E; Synonyms=Truncated; IsoId=Q9UBS5-5; Sequence=VSP_002039; Note=Major isoform in almost all peripheral tissues, although containing a premature stop codon in the mRNA and thus being a potential target for nonsense-mediated mRNA decay. May act as an antagonist of GABA-B receptors, being able to disrupt the normal association between isoform 1A and GABBR2.;
DomainAlpha-helical parts of the C-terminal intracellular region mediate heterodimeric interaction with GABBR2. 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.
FunctionComponent 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. Calcium is required for high affinity binding to GABA. 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. Activated by (-)-baclofen, cgp27492 and blocked by phaclofen.
FunctionIsoform 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.
InteractionO75899:GABBR2; NbExp=2; IntAct=EBI-724156, EBI-715469; P61244:MAX; NbExp=3; IntAct=EBI-724156, EBI-751711; P16333:NCK1; NbExp=3; IntAct=EBI-724156, EBI-389883; P46459:NSF; NbExp=3; IntAct=EBI-724156, EBI-712251;
SimilarityBelongs to the G-protein coupled receptor 3 family. GABA-B receptor subfamily. {ECO:0000305}.
SimilarityContains 2 Sushi (CCP/SCR) domains. {ECO:0000255|PROSITE-ProRule:PRU00302}.
Subcellular LocationCell membrane; Multi-pass membrane protein. Cell junction, synapse, postsynaptic cell membrane; Multi-pass membrane protein. Cell projection, dendrite {ECO:0000250}. Note=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. {ECO:0000250}.
Subcellular LocationIsoform 1E: Secreted {ECO:0000305}.
SubunitHeterodimer of GABBR1 and GABBR2. Homodimers may form, but are inactive. Isoform 1E (without C-terminal intracellular domain) is unable to dimerize via a coiled-coil interaction with GABBR2. Interacts with the leucine zipper of the C-terminal bZIP domain of ATF4 via its C-terminal region. Interacts with JAKMIP1. {ECO:0000269|PubMed:10773016, ECO:0000269|PubMed:14718537, ECO:0000269|PubMed:15617512, ECO:0000269|PubMed:18165688, ECO:0000269|PubMed:22660477, ECO:0000269|PubMed:24305054, ECO:0000269|PubMed:9872316, ECO:0000269|PubMed:9872744}.
Tissue SpecificityHighly expressed in brain and weakly in heart, small intestine and uterus. Isoform 1A is mostly expressed in granular cell and molecular layer. Isoform 1B is mostly expressed in Purkinje cells. Isoform 1E is predominantly expressed in peripheral tissues as kidney, lung, trachea, colon, small intestine, stomach, bone marrow, thymus and mammary gland. {ECO:0000269|PubMed:9844003}.
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