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Target not currently curated in GtoImmuPdb
Target id: 464
Nomenclature: nicotinic acetylcholine receptor α3 subunit
Gene and Protein Information ![]() |
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Species | TM | AA | Chromosomal Location | Gene Symbol | Gene Name | Reference |
Human | 4 | 505 | 15q25.1 | CHRNA3 | cholinergic receptor nicotinic alpha 3 subunit | 5 |
Mouse | 4 | 499 | 9 B | Chrna3 | cholinergic receptor, nicotinic, alpha polypeptide 3 | 3 |
Rat | 4 | 499 | 8q24 | Chrna3 | cholinergic receptor nicotinic alpha 3 subunit | 4 |
Database Links ![]() |
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Alphafold | P32297 (Hs), Q8R4G9 (Mm), P04757 (Rn) |
CATH/Gene3D | 2.70.170.10 |
ChEMBL Target | CHEMBL3068 (Hs), CHEMBL3885609 (Mm), CHEMBL3137276 (Rn), CHEMBL1907587 (Rn), CHEMBL3137275 (Rn), CHEMBL4106146 (Rn), CHEMBL1907593 (Rn) |
DrugBank Target | P32297 (Hs) |
Ensembl Gene | ENSG00000080644 (Hs), ENSMUSG00000032303 (Mm), ENSRNOG00000013829 (Rn) |
Entrez Gene | 1136 (Hs), 110834 (Mm), 25101 (Rn) |
Human Protein Atlas | ENSG00000080644 (Hs) |
KEGG Gene | hsa:1136 (Hs), mmu:110834 (Mm), rno:25101 (Rn) |
OMIM | 118503 (Hs) |
Pharos | P32297 (Hs) |
RefSeq Nucleotide | NM_000743 (Hs), NM_145129 (Mm), NM_052805 (Rn) |
RefSeq Protein | NP_000734 (Hs), NP_660111 (Mm), NP_434692 (Rn) |
UniProtKB | P32297 (Hs), Q8R4G9 (Mm), P04757 (Rn) |
Wikipedia | CHRNA3 (Hs) |
Functional Characteristics ![]() |
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α3β2: PCa/PNa = 1.5; α3β4: PCa/PNa = 0.78 - 1.1, Pf = 2.7 – 4.6% |
Natural/Endogenous Ligands ![]() |
acetylcholine |
Commonly used antagonists (Human) |
α3β2: DHβE (KB = 1.6 μM, IC50 = 2.0 μM), tubocurarine (KB = 2.4 μM); α3β4: DHβE (KB = 19 μM, IC50 = 26 μM), tubocurarine (KB = 2.2 μM) |
Download all structure-activity data for this target as a CSV file
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View species-specific agonist tables |
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Key to terms and symbols | View all chemical structures | Click column headers to sort | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Channel Blockers | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Tissue Distribution ![]() |
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Tissue Distribution Comments | ||||||||||
In situ hybridization of rhesus monkey (Macaca mulatta) brain shows that expression appears to be restricted primarily to the medial habenula with minor expression in the hippocampus [7]. |
Physiological Consequences of Altering Gene Expression ![]() |
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Clinically-Relevant Mutations and Pathophysiology ![]() |
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1. Adams MR, Nikkel AL, Donnelly-Roberts DL, Watt AT, Johnston JF, Cowsert LM, Butler M, Kroeger PE, Frost L, Curzon P et al.. (2004) In vitro and in vivo effects of an alpha3 neuronal nicotinic acetylcholine receptor antisense oligonucleotide. Brain Res Mol Brain Res, 129 (1-2): 67-79. [PMID:15469883]
2. Amos CI, Wu X, Broderick P, Gorlov IP, Gu J, Eisen T, Dong Q, Zhang Q, Gu X, Vijayakrishnan J et al.. (2008) Genome-wide association scan of tag SNPs identifies a susceptibility locus for lung cancer at 15q25.1. Nat Genet, 40 (5): 616-22. [PMID:18385676]
3. Bessis A, Simon-Chazottes D, Devillers-Thiéry A, Guénet JL, Changeux JP. (1990) Chromosomal localization of the mouse genes coding for alpha 2, alpha 3, alpha 4 and beta 2 subunits of neuronal nicotinic acetylcholine receptor. FEBS Lett, 264 (1): 48-52. [PMID:2338144]
4. Boulter J, Evans K, Goldman D, Martin G, Treco D, Heinemann S, Patrick J. (1986) Isolation of a cDNA clone coding for a possible neural nicotinic acetylcholine receptor alpha-subunit. Nature, 319 (6052): 368-74. [PMID:3753746]
5. Fornasari D, Chini B, Tarroni P, Clementi F. (1990) Molecular cloning of human neuronal nicotinic receptor alpha 3-subunit. Neurosci Lett, 111 (3): 351-6. [PMID:2336208]
6. Goldman D, Simmons D, Swanson LW, Patrick J, Heinemann S. (1986) Mapping of brain areas expressing RNA homologous to two different acetylcholine receptor alpha-subunit cDNAs. Proc Natl Acad Sci USA, 83 (11): 4076-80. [PMID:3012549]
7. 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]
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. Jonsson M, Gurley D, Dabrowski M, Larsson O, Johnson EC, Eriksson LI. (2006) Distinct pharmacologic properties of neuromuscular blocking agents on human neuronal nicotinic acetylcholine receptors: a possible explanation for the train-of-four fade. Anesthesiology, 105 (3): 521-33. [PMID:16931985]
10. Malysz J, Grønlien JH, Anderson DJ, Håkerud M, Thorin-Hagene K, Ween H, Wetterstrand C, Briggs CA, Faghih R, Bunnelle WH et al.. (2009) In vitro pharmacological characterization of a novel allosteric modulator of alpha 7 neuronal acetylcholine receptor, 4-(5-(4-chlorophenyl)-2-methyl-3-propionyl-1H-pyrrol-1-yl)benzenesulfonamide (A-867744), exhibiting unique pharmacological profile. J Pharmacol Exp Ther, 330 (1): 257-67. [PMID:19389923]
11. Mandelzys A, Pié B, Deneris ES, Cooper E. (1994) The developmental increase in ACh current densities on rat sympathetic neurons correlates with changes in nicotinic ACh receptor alpha-subunit gene expression and occurs independent of innervation. J Neurosci, 14 (4): 2357-64. [PMID:8158273]
12. 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]
13. Nirogi R, Mohammed AR, Shinde AK, Ravella SR, Bogaraju N, Subramanian R, Mekala VR, Palacharla RC, Muddana N, Thentu JB et al.. (2020) Discovery and Development of 3-(6-Chloropyridine-3-yloxymethyl)-2-azabicyclo[3.1.0]hexane Hydrochloride (SUVN-911): A Novel, Potent, Selective, and Orally Active Neuronal Nicotinic Acetylcholine α4β2 Receptor Antagonist for the Treatment of Depression. J Med Chem, 63 (6): 2833-2853. [PMID:32026697]
14. Poth K, Nutter TJ, Cuevas J, Parker MJ, Adams DJ, Luetje CW. (1997) Heterogeneity of nicotinic receptor class and subunit mRNA expression among individual parasympathetic neurons from rat intracardiac ganglia. J Neurosci, 17 (2): 586-96. [PMID:8987781]
15. Rust G, Burgunder JM, Lauterburg TE, Cachelin AB. (1994) Expression of neuronal nicotinic acetylcholine receptor subunit genes in the rat autonomic nervous system. Eur J Neurosci, 6 (3): 478-85. [PMID:8019684]
16. 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]
17. 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]
18. 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]
19. Thorgeirsson TE, Geller F, Sulem P, Rafnar T, Wiste A, Magnusson KP, Manolescu A, Thorleifsson G, Stefansson H, Ingason A et al.. (2008) A variant associated with nicotine dependence, lung cancer and peripheral arterial disease. Nature, 452 (7187): 638-42. [PMID:18385739]
20. Timmermann DB, Grønlien JH, Kohlhaas KL, Nielsen EØ, Dam E, Jørgensen TD, Ahring PK, Peters D, Holst D, Christensen JK et al.. (2007) An allosteric modulator of the alpha7 nicotinic acetylcholine receptor possessing cognition-enhancing properties in vivo. J Pharmacol Exp Ther, 323 (1): 294-307. [PMID:17625074]
21. Wada E, Wada K, Boulter J, Deneris E, Heinemann S, Patrick J, Swanson LW. (1989) Distribution of alpha 2, alpha 3, alpha 4, and beta 2 neuronal nicotinic receptor subunit mRNAs in the central nervous system: a hybridization histochemical study in the rat. J Comp Neurol, 284 (2): 314-35. [PMID:2754038]
22. 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]
23. Whiteaker P, Peterson CG, Xu W, McIntosh JM, Paylor R, Beaudet AL, Collins AC, Marks MJ. (2002) Involvement of the alpha3 subunit in central nicotinic binding populations. J Neurosci, 22 (7): 2522-9. [PMID:11923417]
24. Xu W, Gelber S, Orr-Urtreger A, Armstrong D, Lewis RA, Ou CN, Patrick J, Role L, De Biasi M, Beaudet AL. (1999) Megacystis, mydriasis, and ion channel defect in mice lacking the alpha3 neuronal nicotinic acetylcholine receptor. Proc Natl Acad Sci USA, 96 (10): 5746-51. [PMID:10318955]