Contents:
- Quaternary Structure
- Gene and Protein Information
- Previous and Unofficial Names
- Database Links
- Agonists
- Antagonists
- Allosteric Modulators
- Transduction Mechanisms
- Tissue Distribution
- Expression Datasets
- Functional Assays
- Physiological Functions
- Phenotypes, Alleles and Disease Models
- References
- Contributors
- How to cite this page
| Quaternary Structure: Complexes |
| GABAB receptor |
Gene and Protein Information  |
||||||
| class C G protein-coupled receptor | ||||||
| Species | TM | AA | Chromosomal Location | Gene Symbol | Gene Name | Reference |
| Human | 7 | 941 | 9q22.33 | GABBR2 | gamma-aminobutyric acid type B receptor subunit 2 | 12,15 |
| Mouse | 7 | 940 | 4 B1 | Gabbr2 | gamma-aminobutyric acid type B receptor subunit 2 | |
| Rat | 7 | 940 | 5q22 | Gabbr2 | gamma-aminobutyric acid type B receptor subunit 2 | |
| Previous and Unofficial Names |
|
| GABABR2 [8-9,12,19] | GABABR2 | HG20 | G protein-coupled receptor 51 | GABA-B R2 receptor | GABA-B receptor 2 | GPR51 [14,16] | GPRC3B | gamma-aminobutyric acid (GABA) B receptor, 2 | gamma-aminobutyric acid (GABA) B receptor 2 | gamma-aminobutyric acid (GABA) B receptor | |
| Database Links |
|
| Specialist databases | |
| GPCRdb | gabr2_human (Hs), gabr2_mouse (Mm), gabr2_rat (Rn) |
| Other databases | |
| Alphafold | O75899 (Hs), Q80T41 (Mm), O88871 (Rn) |
| ChEMBL Target | CHEMBL5034 (Hs), CHEMBL2111474 (Rn) |
| DrugBank Target | O75899 (Hs) |
| Ensembl Gene | ENSG00000136928 (Hs), ENSMUSG00000039809 (Mm), ENSRNOG00000008431 (Rn) |
| Entrez Gene | 9568 (Hs), 242425 (Mm), 83633 (Rn) |
| Human Protein Atlas | ENSG00000136928 (Hs) |
| KEGG Gene | hsa:9568 (Hs), mmu:242425 (Mm), rno:83633 (Rn) |
| OMIM | 607340 (Hs) |
| Pharos | O75899 (Hs) |
| RefSeq Nucleotide | NM_005458 (Hs), NM_001081141 (Mm), NM_031802 (Rn) |
| RefSeq Protein | NP_005449 (Hs), NP_001074610 (Mm), NP_113990 (Rn) |
| UniProtKB | O75899 (Hs), Q80T41 (Mm), O88871 (Rn) |
| Wikipedia | GABBR2 (Hs) |
Download all structure-activity data for this target as a CSV file 
| Agonist Comments | ||
| No evidence of any ligand activating GABAB receptors acting on this subunit. It has been proposed, based on evolutionary trace analysis, that no endogenous ligand binds to GABAB2 within the equivalent site of GABAB1 where agonists act [10]. |
| Antagonist Comments | ||
| So far all competitive antagonists acting at the GABAB heteromeric receptor have been shown to interact exclusively with the GABAB1 subunit. |
| Allosteric Modulators | |||||||||||||||||||||||||||||||||||||||||||||||||||
| Key to terms and symbols | View all chemical structures | Click column headers to sort | |||||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||
| Allosteric Modulator Comments | |||||||||||||||||||||||||||||||||||||||||||||||||||
| CGP7930 is acting as a positive allosteric regulator of the heteromeric GABAB1 - GABAB2 receptor. This compound has been shown to act in the GABAB2 heptahelical domain [1]. GS 39783 has also been shown to be a selective positive allosteric regulator in rats [18] |
|||||||||||||||||||||||||||||||||||||||||||||||||||
| Primary Transduction Mechanisms
|
|
| Comments: The GABAB2 subunit has been shown not to couple to G proteins efficiently when in the absence of GABAB1. However, the GABAB2 subunit contains all the molecular determinants required for G protein recognition and activation by the heterodimer. | |
| References: 2,7 |
| Tissue Distribution
|
||||||||
|
||||||||
|
||||||||
|
||||||||
|
||||||||
|
||||||||
| Tissue Distribution Comments | ||||||||
| GABAB2 has a similar distribution to GABAB1 in the brain except that GABAB2 levels are low in the caudate putamen, hypothalamus, olfactory bulb [3-6,8,11] and in the E11-E17 mouse embryo [13], unlike GABAB1. |
||||||||
| Expression Datasets |
|
|
| Functional Assay Comments |
| So far there is no evidence for the formation of a functional receptor made up exclusively of the GABAB2 subunit. |
| Physiological Functions Comments | |
| So far, there is no indication that a function may be generated exclusively by the GABAB2 subunit, in the absence of GABAB1. Although the GABAB2 subunit can be considered as an orphan subunit since it does not appear to bind any endogenous ligand, its function as a necessary subunit for the formation of a fully functional GABAB heterodimeric receptor is now well established. |
| Phenotypes, Alleles and Disease Models
|
Mouse data from MGI | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
References
1. Binet V, Brajon C, Le Corre L, Acher F, Pin JP, Prézeau L. (2004) The heptahelical domain of GABA(B2) is activated directly by CGP7930, a positive allosteric modulator of the GABA(B) receptor. J Biol Chem, 279 (28): 29085-91. [PMID:15126507]
2. Bowery NG. (1993) GABAB receptor pharmacology. Annu Rev Pharmacol Toxicol, 33: 109-47. [PMID:8388192]
3. Bowery NG, Hudson AL, Price GW. (1987) GABAA and GABAB receptor site distribution in the rat central nervous system. Neuroscience, 20 (2): 365-83. [PMID:3035421]
4. Charles KJ, Evans ML, Robbins MJ, Calver AR, Leslie RA, Pangalos MN. (2001) Comparative immunohistochemical localisation of GABA(B1a), GABA(B1b) andGABA(B2) subunits in rat brain, spinal cord and dorsal root ganglion. Neuroscience, 106: 447-467. [PMID:11591450]
5. Clark JA, Mezey E, Lam AS, Bonner TI. (2000) Distribution of the GABA(B) receptor subunit gb2 in rat CNS. Brain Res, 860: 41-52. [PMID:10727622]
6. Durkin MM, Gunwaldsen CA, Borowsky B, Jones KA, Branchek TA. (1999) An in situ hybridization study of the distribution of the GABA(B2) protein mRNAin the rat CNS. Brain Res Mol Brain Res, 71: 185-200. [PMID:10521573]
7. Hill DR. (1985) GABAB receptor modulation of adenylate cyclase activity in rat brain slices. Br J Pharmacol, 84 (1): 249-57. [PMID:2579700]
8. 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]
9. Kaupmann K, Malitschek B, Schuler V, Heid J, Froestl W, Beck P, Mosbacher J, Bischoff S, Kulik A, Shigemoto R et al.. (1998) GABA(B)-receptor subtypes assemble into functional heteromeric complexes. Nature, 396 (6712): 683-7. [PMID:9872317]
10. 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]
11. 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]
12. Martin SC, Russek SJ, Farb DH. (1999) Molecular identification of the human GABABR2: cell surface expression and coupling to adenylyl cyclase in the absence of GABABR1. Mol Cell Neurosci, 13 (3): 180-91. [PMID:10328880]
13. 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]
14. Massone S, Vassallo I, Fiorino G, Castelnuovo M, Barbieri F, Borghi R, Tabaton M, Robello M, Gatta E, Russo C et al.. (2011) 17A, a novel non-coding RNA, regulates GABA B alternative splicing and signaling in response to inflammatory stimuli and in Alzheimer disease. Neurobiol Dis, 41 (2): 308-17. [PMID:20888417]
15. Ng GY, McDonald T, Bonnert T, Rigby M, Heavens R, Whiting P, Chateauneuf A, Coulombe N, Kargman S, Caskey T et al.. (1999) Cloning of a novel G-protein-coupled receptor GPR 51 resembling GABAB receptors expressed predominantly in nervous tissues and mapped proximal to the hereditary sensory neuropathy type 1 locus on chromosome 9. Genomics, 56 (3): 288-95. [PMID:10087195]
16. Sun D, Huang W, Hwang YY, Zhang Y, Zhang Q, Li MD. (2007) Regulation by nicotine of Gpr51 and Ntrk2 expression in various rat brain regions. Neuropsychopharmacology, 32 (1): 110-6. [PMID:16794563]
17. Urwyler S, Mosbacher J, Lingenhoehl K, Heid J, Hofstetter K, Froestl W, Bettler B, Kaupmann K. (2001) Positive allosteric modulation of native and recombinant gamma-aminobutyric acid(B) receptors by 2,6-Di-tert-butyl-4-(3-hydroxy-2,2-dimethyl-propyl)-phenol (CGP7930) and its aldehyde analog CGP13501. Mol Pharmacol, 60 (5): 963-71. [PMID:11641424]
18. Urwyler S, Pozza MF, Lingenhoehl K, Mosbacher J, Lampert C, Froestl W, Koller M, Kaupmann K. (2003) N,N'-Dicyclopentyl-2-methylsulfanyl-5-nitro-pyrimidine-4,6-diamine (GS39783) and structurally related compounds: novel allosteric enhancers of gamma-aminobutyric acidB receptor function. J Pharmacol Exp Ther, 307 (1): 322-30. [PMID:12954816]
19. White JH, Wise A, Main MJ, Green A, Fraser NJ, Disney GH, Barnes AA, Emson P, Foord SM, Marshall FH. (1998) Heterodimerization is required for the formation of a functional GABA(B) receptor. Nature, 396 (6712): 679-82. [PMID:9872316]
This work is licensed under a Creative Commons Attribution-ShareAlike 4.0 International License