nicotinic acetylcholine receptor β4 subunit
Target id: 474
Nomenclature: nicotinic acetylcholine receptor β4 subunit
Contents:
Gene and Protein Information  |
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| Species | TM | AA | Chromosomal Location | Gene Symbol | Gene Name | Reference |
| Human | 4 | 498 | 15q25.1 | CHRNB4 | cholinergic receptor nicotinic beta 4 subunit | 7 |
| Mouse | 4 | 495 | 9 B | Chrnb4 | cholinergic receptor, nicotinic, beta polypeptide 4 | 3 |
| Rat | 4 | 495 | 8q24 | Chrnb4 | cholinergic receptor nicotinic beta 4 subunit | 2 |
| Previous and Unofficial Names |
| Acrb4 | cholinergic receptor, nicotinic, beta 4 (neuronal) | cholinergic receptor, nicotinic beta 4 | cholinergic receptor |
| Database Links |
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| Alphafold | P30926 (Hs), Q8R493 (Mm), P12392 (Rn) |
| CATH/Gene3D | 2.70.170.10 |
| ChEMBL Target | CHEMBL3137273 (Hs), CHEMBL1907591 (Hs), CHEMBL2109230 (Hs), CHEMBL3137285 (Hs), CHEMBL3038459 (Hs), CHEMBL1907594 (Hs), CHEMBL3885595 (Hs), CHEMBL3885609 (Mm), CHEMBL3301382 (Mm), CHEMBL2658 (Rn) |
| DrugBank Target | P30926 (Hs) |
| Ensembl Gene | ENSG00000117971 (Hs), ENSMUSG00000035200 (Mm), ENSRNOG00000014427 (Rn) |
| Entrez Gene | 1143 (Hs), 108015 (Mm), 25103 (Rn) |
| Human Protein Atlas | ENSG00000117971 (Hs) |
| KEGG Gene | hsa:1143 (Hs), mmu:108015 (Mm), rno:25103 (Rn) |
| OMIM | 118509 (Hs) |
| Pharos | P30926 (Hs) |
| RefSeq Nucleotide | NM_000750 (Hs), NM_148944 (Mm), NM_052806 (Rn) |
| RefSeq Protein | NP_000741 (Hs), NP_683746 (Mm), NP_434693 (Rn) |
| UniProtKB | P30926 (Hs), Q8R493 (Mm), P12392 (Rn) |
| Wikipedia | CHRNB4 (Hs) |
| Natural/Endogenous Ligands |
| acetylcholine |
| Immuno Process Associations | ||
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| Tissue Distribution
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| Tissue Distribution Comments | ||||||||||
| Deletion of β4 subunit in knockout mice has little effect on total [3H]- or [125I]-epibatidine binding with the exception of a partial reduction in the signal intensity in the fasiculus retroflexus, interpeduncular nucleus and the inferior colliculus. The effects of β4 gene deletion were more readily observable when cytisine was included in the incubation with [3H]- or [125I]-epibatidine. Under these experimental conditions, robust effects could be observed in the medial habenula, the fasiculus retroflexis, the interpeducular nucleus and the inferior colliculus, all of which expressed high levels of cytisine-resistant [125I]epibatidine binding [1,10]. Expression of β4 mRNA in rhesus monkey (Macaca mulatta) brain is similar to that described in rodents. High expression is detected in thalamic nuclei, substantia nigra pars compacta and vertral tegmental area. Expression is also detected in cortex (layer VI showing the highest level of expression) and lower levles in hippocampus and caudate [4]. Expression of β4 mRNA in suirrel monkey (Samimiri sciureus) appears to differ from that in rodents or macaques. High levels of expression brain have been detected in caudate, putamen and hippocampus. However, compared to expression levels in the cotex, levels of expression were relatively low in thalamic nuclei, substantia nigra pars compacta and medial habenula [6]. |
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| Physiological Consequences of Altering Gene Expression
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| Clinically-Relevant Mutations and Pathophysiology
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References
1. Baddick CG, Marks MJ. (2011) An auroradiographic survey of mouse brain nicotinic acetylcholine receptors defined by null mutants. Biochem Pharmacol,,. [PMID:21575611]
2. Duvoisin RM, Deneris ES, Patrick J, Heinemann S. (1989) The functional diversity of the neuronal nicotinic acetylcholine receptors is increased by a novel subunit: beta 4. Neuron, 3 (4): 487-96. [PMID:2642007]
3. Eng CM, Kozak CA, Beaudet AL, Zoghbi HY. (1991) Mapping of multiple subunits of the neuronal nicotinic acetylcholine receptor to chromosome 15 in man and chromosome 9 in mouse. Genomics, 9 (2): 278-82. [PMID:2004777]
4. Han ZY, Le Novère N, Zoli M, Hill JA, Champtiaux N, Changeux JP. (2000) Localization of nAChR subunit mRNAs in the brain of Macaca mulatta. Eur J Neurosci, 12 (10): 3664-74. [PMID:11029636]
5. Kedmi M, Beaudet AL, Orr-Urtreger A. (2004) Mice lacking neuronal nicotinic acetylcholine receptor beta4-subunit and mice lacking both alpha5- and beta4-subunits are highly resistant to nicotine-induced seizures. Physiol Genomics, 17 (2): 221-9. [PMID:14996991]
6. Quik M, Polonskaya Y, Gillespie A, Jakowec M, Lloyd GK, Langston JW. (2000) Localization of nicotinic receptor subunit mRNAs in monkey brain by in situ hybridization. J Comp Neurol, 425 (1): 58-69. [PMID:10940942]
7. Raimondi E, Rubboli F, Moralli D, Chini B, Fornasari D, Tarroni P, De Carli L, Clementi F. (1992) Chromosomal localization and physical linkage of the genes encoding the human alpha 3, alpha 5, and beta 4 neuronal nicotinic receptor subunits. Genomics, 12 (4): 849-50. [PMID:1572664]
8. Sabatelli M, Eusebi F, Al-Chalabi A, Conte A, Madia F, Luigetti M, Mancuso I, Limatola C, Trettel F, Sobrero F et al.. (2009) Rare missense variants of neuronal nicotinic acetylcholine receptor altering receptor function are associated with sporadic amyotrophic lateral sclerosis. Hum Mol Genet, 18 (20): 3997-4006. [PMID:19628475]
9. Salas R, Cook KD, Bassetto L, De Biasi M. (2004) The alpha3 and beta4 nicotinic acetylcholine receptor subunits are necessary for nicotine-induced seizures and hypolocomotion in mice. Neuropharmacology, 47 (3): 401-7. [PMID:15275829]
10. Salas R, Pieri F, De Biasi M. (2004) Decreased signs of nicotine withdrawal in mice null for the beta4 nicotinic acetylcholine receptor subunit. J Neurosci, 24 (45): 10035-9. [PMID:15537871]
11. Salas R, Pieri F, Fung B, Dani JA, De Biasi M. (2003) Altered anxiety-related responses in mutant mice lacking the beta4 subunit of the nicotinic receptor. J Neurosci, 23 (15): 6255-63. [PMID:12867510]
12. Wang N, Orr-Urtreger A, Chapman J, Rabinowitz R, Korczyn AD. (2003) Deficiency of nicotinic acetylcholine receptor beta 4 subunit causes autonomic cardiac and intestinal dysfunction. Mol Pharmacol, 63 (3): 574-80. [PMID:12606764]
13. Whiteaker P, Jimenez M, McIntosh JM, Collins AC, Marks MJ. (2000) Identification of a novel nicotinic binding site in mouse brain using [(125)I]-epibatidine. Br J Pharmacol, 131 (4): 729-39. [PMID:11030722]
14. Xu C, Lu Y, Tang G, Wang R. (1999) Expression of voltage-dependent K(+) channel genes in mesenteric artery smooth muscle cells. Am J Physiol, 277 (5): G1055-63. [PMID:10564112]
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