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nicotinic acetylcholine receptor α5 subunit

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Target not currently curated in GtoImmuPdb

Target id: 466

Nomenclature: nicotinic acetylcholine receptor α5 subunit

Family: Nicotinic acetylcholine receptors

Contents:

Gene and Protein Information Click here for help
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human 4 468 15q25.1 CHRNA5 cholinergic receptor nicotinic alpha 5 subunit 4
Mouse 4 467 9 29.84 cM Chrna5 cholinergic receptor, nicotinic, alpha polypeptide 5 4
Rat 4 452 8q24 Chrna5 cholinergic receptor nicotinic alpha 5 subunit 2
Previous and Unofficial Names Click here for help
neuronal acetylcholine receptor subunit alpha-5 | Acra5 | cholinergic receptor, nicotinic, alpha 5 (neuronal) | cholinergic receptor, nicotinic alpha 5 | cholinergic receptor
Database Links Click here for help
CATH/Gene3D 2.70.170.10
ChEMBL Target CHEMBL3137273 (Hs), CHEMBL3137272 (Hs), CHEMBL3038461 (Hs), CHEMBL3350222 (Mm), CHEMBL4106146 (Rn)
Ensembl Gene ENSG00000169684 (Hs), ENSMUSG00000035594 (Mm), ENSRNOG00000013610 (Rn)
Entrez Gene 1138 (Hs), 110835 (Mm), 25102 (Rn)
Human Protein Atlas ENSG00000169684 (Hs)
KEGG Gene hsa:1138 (Hs), mmu:110835 (Mm), rno:25102 (Rn)
OMIM 118505 (Hs)
Pharos P30532 (Hs)
RefSeq Nucleotide NM_000745 (Hs), NM_176844 (Mm), NM_017078 (Rn)
RefSeq Protein NP_000736 (Hs), NP_789814 (Mm), NP_058774 (Rn)
UniProtKB P30532 (Hs), Q2MKA5 (Mm), P20420 (Rn)
Wikipedia CHRNA5 (Hs)
Natural/Endogenous Ligands Click here for help
acetylcholine

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Antagonists
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Reference
α-conotoxin MII Peptide Click here for species-specific activity table Hs Antagonist - -
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α-conotoxin PnIA Peptide Click here for species-specific activity table Hs Antagonist - -
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α-conotoxin-GIC Peptide Click here for species-specific activity table Hs Antagonist - -
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α-conotoxin TxIA Peptide Click here for species-specific activity table Hs Antagonist - -
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Tissue Distribution Click here for help
Brain:-
Expression of α5 subunit mRNA in mouse is similar to that in rat brain (above), but has also been detected in the medial habenula.
Species:  Mouse
Technique:  in situ hybridisation
References:  11
Brain:-
Studies with wild-type and α5 knockout mice demonstrate that α5-containing nAChRs are present in the cortex, hippocampus, hypothalamus, inferior colliculus, interpeduncular nucleus, medial habenula, olfactory bulb, olfactory tubercle and striatum.
Species:  Mouse
Technique:  Immunoprecipitation, radioligand binding
References:  3
Brain:-
Expression of α5 subunit mRNA has been detected in olfactory bulbs, deep cortical layers (layer VI), hippocampus, interpeduncular nucleus, substantia nigra pars compacta, ventral tegmental area and discrete brainstem nuclei.
Species:  Rat
Technique:  in situ hybridisation
References:  14
Physiological Consequences of Altering Gene Expression Click here for help
Knockdown of α5 expression in the medial habenula results in increased nicotine intake in self-administration tests.
Species:  Rat
Tissue:  in vivo
Technique:  Antisense knockdown
References:  6
Knockout mice display no obvious physical or neurological deficts. Impairment of cardiac parasympathetic ganglionic transmission is observed during high frequencey vagal stimulation. The importance of the α5 subunit in nAChRs expressed in autonomic ganglia is reflected in changes in pharmacological properties of these receptors. Other autonomic effects include increased oxotremorine-induced salivation and tremor.
Species:  Mouse
Tissue:  in vivo
Technique:  Knockout
References:  5,15-16
Reduced sensitivity to nicotine-induced behavioral effects and nicotine-induced seizures are observed in α5 knockout mice. Other effects include reduced sensitivity to the initial effects of nicotine in antinociception, locomotor activity and hypothermia.
Species:  Mouse
Tissue:  in vivo
Technique:  Knockout
References:  9,13
Increased attentional performance has been reported in α5 knockout mice.
Species:  Mouse
Tissue:  in vivo
Technique:  Knockout
References:  1
Increased nicotine intake is observed with α5 knockout mice in self-administration tests. This effect is 'rescued' by re-expression of α5 in medial habenula.
Species:  Mouse
Tissue:  in vivo
Technique:  Knockout
References:  6
Clinically-Relevant Mutations and Pathophysiology Click here for help
Disease:  Nicotine dependence, susceptibility to
Disease Ontology: DOID:0050742
OMIM: 612052
Role:  Single nucleotide polymorphisms in this gene are associated with susceptibility to nicotine dependence and lung cancer.
References:  7-8,10,12
Click column headers to sort
Type Species Amino acid change Nucleotide change Description Reference
Missense Human D398N 10

References

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1. Bailey CD, De Biasi M, Fletcher PJ, Lambe EK. (2010) The nicotinic acetylcholine receptor alpha5 subunit plays a key role in attention circuitry and accuracy. J. Neurosci., 30 (27): 9241-52. [PMID:20610759]

2. Boulter J, O'Shea-Greenfield A, Duvoisin RM, Connolly JG, Wada E, Jensen A, Gardner PD, Ballivet M, Deneris ES, McKinnon D et al.. (1990) Alpha 3, alpha 5, and beta 4: three members of the rat neuronal nicotinic acetylcholine receptor-related gene family form a gene cluster. J. Biol. Chem., 265 (8): 4472-82. [PMID:1689727]

3. Brown RW, Collins AC, Lindstrom JM, Whiteaker P. (2007) Nicotinic alpha5 subunit deletion locally reduces high-affinity agonist activation without altering nicotinic receptor numbers. J. Neurochem., 103 (1): 204-15. [PMID:17573823]

4. 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]

5. Fischer H, Orr-Urtreger A, Role LW, Huck S. (2005) Selective deletion of the alpha5 subunit differentially affects somatic-dendritic versus axonally targeted nicotinic ACh receptors in mouse. J. Physiol. (Lond.), 563 (Pt 1): 119-37. [PMID:15611037]

6. Fowler CD, Lu Q, Johnson PM, Marks MJ, Kenny PJ. (2011) Habenular α5 nicotinic receptor subunit signalling controls nicotine intake. Nature, 471 (7340): 597-601. [PMID:21278726]

7. Hung RJ, McKay JD, Gaborieau V, Boffetta P, Hashibe M, Zaridze D, Mukeria A, Szeszenia-Dabrowska N, Lissowska J, Rudnai P et al.. (2008) A susceptibility locus for lung cancer maps to nicotinic acetylcholine receptor subunit genes on 15q25. Nature, 452 (7187): 633-7. [PMID:18385738]

8. Improgo MR, Scofield MD, Tapper AR, Gardner PD. (2010) The nicotinic acetylcholine receptor CHRNA5/A3/B4 gene cluster: dual role in nicotine addiction and lung cancer. Prog. Neurobiol., 92 (2): 212-26. [PMID:20685379]

9. Jackson KJ, Marks MJ, Vann RE, Chen X, Gamage TF, Warner JA, Damaj MI. (2010) Role of alpha5 nicotinic acetylcholine receptors in pharmacological and behavioral effects of nicotine in mice. J. Pharmacol. Exp. Ther., 334 (1): 137-46. [PMID:20400469]

10. Kuryatov A, Berrettini W, Lindstrom J. (2011) Acetylcholine receptor (AChR) α5 subunit variant associated with risk for nicotine dependence and lung cancer reduces (α4β2)₂α5 AChR function. Mol. Pharmacol., 79 (1): 119-25. [PMID:20881005]

11. Marks MJ, Pauly JR, Gross SD, Deneris ES, Hermans-Borgmeyer I, Heinemann SF, Collins AC. (1992) Nicotine binding and nicotinic receptor subunit RNA after chronic nicotine treatment. J. Neurosci., 12 (7): 2765-84. [PMID:1613557]

12. Saccone SF, Hinrichs AL, Saccone NL, Chase GA, Konvicka K, Madden PA, Breslau N, Johnson EO, Hatsukami D, Pomerleau O et al.. (2007) Cholinergic nicotinic receptor genes implicated in a nicotine dependence association study targeting 348 candidate genes with 3713 SNPs. Hum. Mol. Genet., 16 (1): 36-49. [PMID:17135278]

13. Salas R, Orr-Urtreger A, Broide RS, Beaudet A, Paylor R, De Biasi M. (2003) The nicotinic acetylcholine receptor subunit alpha 5 mediates short-term effects of nicotine in vivo. Mol. Pharmacol., 63 (5): 1059-66. [PMID:12695534]

14. Wada E, McKinnon D, Heinemann S, Patrick J, Swanson LW. (1990) The distribution of mRNA encoded by a new member of the neuronal nicotinic acetylcholine receptor gene family (alpha 5) in the rat central nervous system. Brain Res., 526 (1): 45-53. [PMID:2078817]

15. Wang N, Orr-Urtreger A, Chapman J, Rabinowitz R, Korczyn AD. (2004) Nicotinic acetylcholine receptor alpha5 subunits modulate oxotremorine-induced salivation and tremor. J. Neurol. Sci., 222 (1-2): 87-91. [PMID:15240201]

16. Wang N, Orr-Urtreger A, Chapman J, Rabinowitz R, Nachman R, Korczyn AD. (2002) Autonomic function in mice lacking alpha5 neuronal nicotinic acetylcholine receptor subunit. J. Physiol. (Lond.), 542 (Pt 2): 347-54. [PMID:12122136]

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