Human Gene GABBR1 (uc011goy.2) Description and Page Index
Description: Homo sapiens gamma-aminobutyric acid (GABA) B receptor, 1 (GABBR1), transcript variant 1, mRNA. RefSeq Summary (NM_021903): Gamma-aminobutyric acid (GABA) is the main inhibitory neurotransmitter in the mammalian central nervous system. GABA exerts its effects through ionotropic [GABA(A/C)] receptors, to produce fast synaptic inhibition, and metabotropic [GABA(B)] receptors, to produce slow, prolonged inhibitory signals. The GABA(B) receptor consists of a heterodimer of two related 7-transmembrane receptors, GABA(B) receptor 1 and GABA(B) receptor 2. The GABA(B) receptor 1 gene is mapped to chromosome 6p21.3 within the HLA class I region close to the HLA-F gene. Susceptibility loci for multiple sclerosis, epilepsy, and schizophrenia have also been mapped in this region. Alternative splicing of this gene generates multiple transcript variants. [provided by RefSeq, Jun 2009]. Transcript (Including UTRs) Position: chr6_mann_hap4:873,029-903,954 Size: 30,926 Total Exon Count: 23 Strand: - Coding Region Position: chr6_mann_hap4:874,344-898,375 Size: 24,032 Coding Exon Count: 18
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Comments and Description Text from UniProtKB
ID:GABR1_HUMAN DESCRIPTION: RecName: Full=Gamma-aminobutyric acid type B receptor subunit 1; Short=GABA-B receptor 1; Short=GABA-B-R1; Short=GABA-BR1; Short=GABABR1; Short=Gb1; Flags: Precursor; 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. 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. FUNCTION: 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. SUBUNIT: Heterodimer 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. INTERACTION: 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; SUBCELLULAR LOCATION: Cell membrane; Multi-pass membrane protein. Cell junction, synapse, postsynaptic cell membrane; Multi-pass membrane protein. Cell projection, dendrite (By similarity). 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. SUBCELLULAR LOCATION: Isoform 1E: Secreted (Probable). TISSUE SPECIFICITY: Highly 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. DOMAIN: Alpha-helical parts of the C-terminal intracellular region mediate heterodimeric interaction with GABA-B receptor 2. The linker region between the transmembrane domain 3 (TM3) and the transmembrane domain 4 (TM4) probably play a role in the specificity for G-protein coupling. SIMILARITY: Belongs to the G-protein coupled receptor 3 family. GABA-B receptor subfamily. SIMILARITY: Contains 2 Sushi (CCP/SCR) domains.
Genetic Association Studies of Complex Diseases and Disorders
schizophrenia Zai, G. et al. 2005, Possible association between the gamma-aminobutyric acid type B receptor 1 (GABBR1) gene and schizophrenia., European neuropsychopharmacology. 2005 May;15(3):347-52.
Further investigations of the role of GABBR1 in SCZ are warranted.
schizophrenia Zhao, X. et al. 2007, Systematic study of association of four GABAergic genes, Schizophr Res 2007.
sleep apnea Bayazit, Y. A. et al. 2007, Association of GABA(B)R1 Receptor Gene Polymorphism with Obstructive Sleep Apnea Syndrome, ORL J Otorhinolaryngol Relat Spec 2007 69(3) 190-197.
The Ala20Val polymorphism of the GABA(B)R1 gene may be associated with OSAS, whereas Gly489Ser polymorphism does not seem to be involved in OSAS.
The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.
Pfam Domains: PF00003 - 7 transmembrane receptor (metabotropic glutamate family) PF01094 - Receptor family ligand binding region
SCOP Domains: 53822 - Periplasmic binding protein-like I
ModBase Predicted Comparative 3D Structure on Q9UBS5
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Orthologous Genes in Other Species
Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.