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| Quaternary Structure: Complexes |
| GABAB receptor |
Gene and Protein Information  |
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| class C G protein-coupled receptor | ||||||
| Species | TM | AA | Chromosomal Location | Gene Symbol | Gene Name | Reference |
| Human | 7 | 961 | 6p22.1 | GABBR1 | gamma-aminobutyric acid type B receptor subunit 1 | 10-11,21 |
| Mouse | 7 | 960 | 17 19.16 cM | Gabbr1 | gamma-aminobutyric acid type B receptor subunit 1 | |
| Rat | 7 | 991 | 20p12 | Gabbr1 | gamma-aminobutyric acid type B receptor subunit 1 | |
| Previous and Unofficial Names |
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| GABABR1 [14] | GPRC3A | GABA-B receptor 1 | GABABR1 | gamma-aminobutyric acid (GABA) B receptor 1 | gamma-aminobutyric acid (GABA) B receptor | |
| Database Links |
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| Specialist databases | |
| GPCRdb | gabr1_human (Hs), gabr1_mouse (Mm), gabr1_rat (Rn) |
| Other databases | |
| Alphafold | Q9UBS5 (Hs), Q9WV18 (Mm), Q9Z0U4 (Rn) |
| ChEMBL Target | CHEMBL2064 (Hs), CHEMBL2753 (Rn) |
| DrugBank Target | Q9UBS5 (Hs) |
| Ensembl Gene | ENSG00000204681 (Hs), ENSMUSG00000024462 (Mm), ENSRNOG00000000774 (Rn) |
| Entrez Gene | 2550 (Hs), 54393 (Mm), 81657 (Rn) |
| Human Protein Atlas | ENSG00000204681 (Hs) |
| KEGG Gene | hsa:2550 (Hs), mmu:54393 (Mm), rno:81657 (Rn) |
| OMIM | 603540 (Hs) |
| Pharos | Q9UBS5 (Hs) |
| RefSeq Nucleotide | NM_001470 (Hs), NM_019439 (Mm), NM_031028 (Rn) |
| RefSeq Protein | NP_001461 (Hs), NP_062312 (Mm), NP_112290 (Rn) |
| UniProtKB | Q9UBS5 (Hs), Q9WV18 (Mm), Q9Z0U4 (Rn) |
| Wikipedia | GABBR1 (Hs) |
| Natural/Endogenous Ligands |
| GABA |
Download all structure-activity data for this target as a CSV file 
| Agonists | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Key to terms and symbols | View all chemical structures | Click column headers to sort | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| View species-specific agonist tables | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Agonist Comments | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| The potency values displayed here are for ligand binding to the GABAB1 subunit only. For ligand binding data on the functional heterodimer of GABAB1 and GABAB2, see the GABAB data pages. No evidence of any species difference. The GABA binding site within this subunit is located in the large extracellular domain, the structure of which is similar to that of the mGlu receptor. Critical residues involved in agonist binding have been identified by molecular modeling and site directed mutagenesis [15]. It is proposed agonists act by stabilizing a closed state of this binding domain in GABAB1. In agreement with this proposal, locking this binding domain in a closed state by introduction of a cystein-bond, locks the receptor in a fully active state [16]. |
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| Antagonists | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Key to terms and symbols | View all chemical structures | Click column headers to sort | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Antagonist Comments | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| The potency values displayed here are for ligand binding to the GABAB1 subunit only. For ligand binding data on the functional heterodimer of GABAB1 and GABAB2, see the GABAB data pages. So far no species difference have been noticed for the GABAB1 subunit. These antagonists bind at the same site as agonists and likely prevent the formation of a closed state of the binding domain. When measured on the GABAB1 subunit expressed alone, antagonist affinities were identical to those measured in the GABAB1 - GABAB2 heterodimer. This indicates that the GABAB2 subunit has no major effect on antagonist binding. |
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| Allosteric Modulator Comments | ||
| Positive modulators for GABAB receptors exist but the indications are that they exert their actions via GABAB2 within the GABAB heterodimer. No evidence for any modulation of the GABAB1 receptor subunit exists. |
| Primary Transduction Mechanisms
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| Comments: The GABAB2 subunit contains all the molecular determinants required for G protein recognition and activation by the heteromer[6,8,17]. However, GABAB1 is able to weakly couple to G proteins and to atypically modulate effector K+ channels in vivo in the absence of GABAB2. It is currently unclear whether the observed coupling is physiologically relevant or not. | |
| References: 9 |
| Tissue Distribution
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| Tissue Distribution Comments | ||||||||
| There is a high degree of similarity between the distributions of the GABAB1 and GABAB2 subunits [13]. | ||||||||
| Expression Datasets |
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| Functional Assay Comments |
| No functional assays for the GABAB1 (in the absence of GABAB2) subunit have been described. Only where there is an intact heterodimer (GABAB1+ GABAB2) have any functional studies been reported. Structural modifications to GABAB1 + GABAB2 within the heterodimer can still allow functional responses to occur. |
| Physiological Consequences of Altering Gene Expression
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| Phenotypes, Alleles and Disease Models
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Mouse data from MGI | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Biologically Significant Variants
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1. AstraZeneca. Lesogaberan (AZD3355). Accessed on 11/09/2014. Modified on 11/09/2014. astrazeneca.com, http://openinnovation.astrazeneca.com/what-we-offer/compound/azd3355-lesogaberan/
2. Bolser DC, Blythin DJ, Chapman RW, Egan RW, Hey JA, Rizzo C, Kuo SC, Kreutner W. (1995) The pharmacology of SCH 50911: a novel, orally-active GABA-beta receptor antagonist. J Pharmacol Exp Ther, 274 (3): 1393-8. [PMID:7562513]
3. Brown JT, Gill CH, Farmer CE, Lanneau C, Randall AD, Pangalos MN, Collingridge GL, Davies CH. (2003) Mechanisms contributing to the exacerbated epileptiform activity in hippocampal slices of GABAB1 receptor subunit knockout mice. Epilepsy Res, 57 (2-3): 121-36. [PMID:15013053]
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6. Duthey B, Caudron S, Perroy J, Bettler B, Fagni L, Pin JP, Prézeau L. (2002) A single subunit (GB2) is required for G-protein activation by the heterodimeric GABA(B) receptor. J Biol Chem, 277 (5): 3236-41. [PMID:11711539]
7. Froestl W, Mickel SJ, von Sprecher G, Diel PJ, Hall RG, Maier L, Strub D, Melillo V, Baumann PA, Bernasconi R et al.. (1995) Phosphinic acid analogues of GABA. 2. Selective, orally active GABAB antagonists. J Med Chem, 38 (17): 3313-31. [PMID:7650685]
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9. Gassmann M, Shaban H, Vigot R, Sansig G, Haller C, Barbieri S, Humeau Y, Schuler V, Muller M, Kinzel B, Klebs K, Schmutz M, Froestl W, Heid J, Kelly PH, Gentry C, Jaton AL, van der Putten H, Mombereau C, Lecourtier L, Mosbacher J, Cryan JF, Fritschy JM, Luthi A, Kaupmann K, Bettler B. (2004) Redistribution of GABAB(1) protein and atypical GABAB responses in GABAB(2)-deficient mice. J Neurosci, 24: 6086-6097. [PMID:15240800]
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12. Isomoto S, Kaibara M, Sakurai-Yamashita Y, Nagayama Y, Uezono Y, Yano K, Taniyama K. (1998) Cloning and tissue distribution of novel splice variants of the rat GABAB receptor. Biochem Biophys Res Commun, 253 (1): 10-5. [PMID:9875211]
13. Jones KA, Borowsky B, Tamm JA, Craig DA, Durkin MM, Dai M, Yao WJ, Johnson M, Gunwaldsen C, Huang LY et al.. (1998) GABA(B) receptors function as a heteromeric assembly of the subunits GABA(B)R1 and GABA(B)R2. Nature, 396 (6712): 674-9. [PMID:9872315]
14. Kaupmann K, Huggel K, Heid J, Flor PJ, Bischoff S, Mickel SJ, McMaster G, Angst C, Bittiger H, Froestl W et al.. (1997) Expression cloning of GABA(B) receptors uncovers similarity to metabotropic glutamate receptors. Nature, 386 (6622): 239-46. [PMID:9069281]
15. Kniazeff J, Galvez T, Labesse G, Pin JP. (2002) No ligand binding in the GB2 subunit of the GABA(B) receptor is required for activation and allosteric interaction between the subunits. J Neurosci, 22 (17): 7352-61. [PMID:12196556]
16. Kniazeff J, Saintot PP, Goudet C, Liu J, Charnet A, Guillon G, Pin JP. (2004) Locking the dimeric GABA(B) G-protein-coupled receptor in its active state. J Neurosci, 24 (2): 370-7. [PMID:14724235]
17. Margeta-Mitrovic M, Jan YN, Jan LY. (2001) Function of GB1 and GB2 subunits in G protein coupling of GABA(B) receptors. Proc Natl Acad Sci USA, 98 (25): 14649-54. [PMID:11724956]
18. Margeta-Mitrovic M, Mitrovic I, Riley RC, Jan LY, Basbaum AI. (1999) Immunohistochemical localization of GABA(B) receptors in the rat central nervous system. J Comp Neurol, 405 (3): 299-321. [PMID:10076927]
19. Martin SC, Russek SJ, Farb DH. (2001) Human GABA(B)R genomic structure: evidence for splice variants in GABA(B)R1 but not GABA(B)R2. Gene, 278: 63-79. [PMID:11707323]
20. Martin SC, Steiger JL, Gravielle MC, Lyons HR, Russek SJ, Farb DH. (2004) Differential expression of gamma-aminobutyric acid type B receptor subunit mRNAs in the developing nervous system and receptor coupling to adenylyl cyclase in embryonic neurons. J Comp Neurol, 473: 16-29. [PMID:15067715]
21. Peters HC, Kämmer G, Volz A, Kaupmann K, Ziegler A, Bettler B, Epplen JT, Sander T, Riess O. (1998) Mapping, genomic structure, and polymorphisms of the human GABABR1 receptor gene: evaluation of its involvement in idiopathic generalized epilepsy. Neurogenetics, 2 (1): 47-54. [PMID:9933300]
22. Pfaff T, Malitschek B, Kaupmann K, Prézeau L, Pin JP, Bettler B, Karschin A. (1999) Alternative splicing generates a novel isoform of the rat metabotropic GABA(B)R1 receptor. Eur J Neurosci, 11 (8): 2874-82. [PMID:10457184]
23. Prosser HM, Gill CH, Hirst WD, Grau E, Robbins M, Calver A, Soffin EM, Farmer CE, Lanneau C, Gray J et al.. (2001) Epileptogenesis and enhanced prepulse inhibition in GABA(B1)-deficient mice. Mol Cell Neurosci, 17 (6): 1059-70. [PMID:11414794]
24. Quéva C, Bremner-Danielsen M, Edlund A, Ekstrand AJ, Elg S, Erickson S, Johansson T, Lehmann A, Mattsson JP. (2003) Effects of GABA agonists on body temperature regulation in GABA(B(1))-/- mice. Br J Pharmacol, 140 (2): 315-22. [PMID:12970075]
25. Schuler V, Lüscher C, Blanchet C, Klix N, Sansig G, Klebs K, Schmutz M, Heid J, Gentry C, Urban L et al.. (2001) Epilepsy, hyperalgesia, impaired memory, and loss of pre- and postsynaptic GABA(B) responses in mice lacking GABA(B(1)). Neuron, 31 (1): 47-58. [PMID:11498050]
26. Schwarz DA, Barry G, Eliasof SD, Petroski RE, Conlon PJ, Maki RA. (2000) Characterization of gamma-aminobutyric acid receptor GABAB(1e), a GABAB(1) splice variant encoding a truncated receptor. J Biol Chem, 275 (41): 32174-81. [PMID:10906333]
27. Steiger JL, Bandyopadhyay S, Farb DH, Russek SJ. (2004) cAMP response element-binding protein, activating transcription factor-4, and upstream stimulatory factor differentially control hippocampal GABABR1a and GABABR1b subunit gene expression through alternative promoters. J Neurosci, 24 (27): 6115-26. [PMID:15240803]
28. Wei K, Eubanks JH, Francis J, Jia Z, Snead 3rd OC. (2001) Cloning and tissue distribution of a novel isoform of the rat GABA(B)R1 receptor subunit. Neuroreport, 12 (4): 833-7. [PMID:11277592]
29. Wei K, Jia Z, Wang YT, Yang J, Liu CC, Snead 3rd OC. (2001) Cloning and characterization of a novel variant of rat GABA(B)R1 with a truncated C-terminus. Brain Res Mol Brain Res, 89 (1-2): 103-10. [PMID:11311980]
