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nicotinic acetylcholine receptor α2 subunit

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Target not currently curated in GtoImmuPdb

Target id: 463

Nomenclature: nicotinic acetylcholine receptor α2 subunit

Family: Nicotinic acetylcholine receptors (nACh)

Contents:

Gene and Protein Information Click here for help
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human 4 529 8p21.2 CHRNA2 cholinergic receptor nicotinic alpha 2 subunit 14
Mouse 4 512 14 34.36 cM Chrna2 cholinergic receptor nicotinic alpha 2 subunit 2
Rat 4 511 15p12 Chrna2 cholinergic receptor nicotinic alpha 2 subunit 12
Previous and Unofficial Names Click here for help
neuronal acetylcholine receptor subunit alpha-2 | Acra2 | cholinergic receptor, nicotinic, alpha 2 (neuronal) | cholinergic receptor, nicotinic alpha 2 | cholinergic receptor, nicotinic, alpha 2 | cholinergic receptor
Database Links Click here for help
Alphafold Q15822 (Hs), Q91X60 (Mm), P12389 (Rn)
CATH/Gene3D 2.70.170.10
ChEMBL Target CHEMBL2109236 (Hs), CHEMBL2109230 (Hs), CHEMBL3350222 (Mm), CHEMBL2584 (Rn)
DrugBank Target Q15822 (Hs)
Ensembl Gene ENSG00000120903 (Hs), ENSMUSG00000022041 (Mm), ENSRNOG00000017424 (Rn)
Entrez Gene 1135 (Hs), 110902 (Mm), 170945 (Rn)
Human Protein Atlas ENSG00000120903 (Hs)
KEGG Gene hsa:1135 (Hs), mmu:110902 (Mm), rno:170945 (Rn)
OMIM 118502 (Hs)
Orphanet ORPHA159345 (Hs)
Pharos Q15822 (Hs)
RefSeq Nucleotide NM_000742 (Hs), NM_144803 (Mm), NM_133420 (Rn)
RefSeq Protein NP_000733 (Hs), NP_659052 (Mm), NP_596911 (Rn)
UniProtKB Q15822 (Hs), Q91X60 (Mm), P12389 (Rn)
Wikipedia CHRNA2 (Hs)
Functional Characteristics Click here for help
α2β2: PCa/PNa ~ 1.5
Natural/Endogenous Ligands Click here for help
acetylcholine
Commonly used antagonists (Human)
α2β2: DHβE (KB = 0.9 μM), tubocurarine (KB = 1.4 μM); α2β4: DHβE (KB = 3.6 μM), tubocurarine (KB = 4.2 μM)

Download all structure-activity data for this target as a CSV file go icon to follow link

Agonists
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Reference
[125I]epibatidine Small molecule or natural product Click here for species-specific activity table Ligand is labelled Ligand is radioactive Rn Full agonist 10.1 – 11.0 pKd
⤷ pKd 10.7 – 11.0 (Kd 2.1x10-11 – 1x10-11 M) α2β2
pKd 10.1 – 10.1 (Kd 8.7x10-11 – 8.4x10-11 M) α2β4
[3H]epibatidine Small molecule or natural product Click here for species-specific activity table Ligand is labelled Ligand is radioactive Rn Full agonist 10.1 – 11.0 pKd
⤷ pKd 10.7 – 11.0 (Kd 2.1x10-11 – 1x10-11 M) α2β2
pKd 10.1 – 10.1 (Kd 8.7x10-11 – 8.4x10-11 M) α2β4
[125I]epibatidine Small molecule or natural product Click here for species-specific activity table Ligand is labelled Ligand is radioactive Hs Full agonist 10.4 pKd
⤷ pKd 10.4 (Kd 4.2x10-11 M) α2β4
[3H]epibatidine Small molecule or natural product Click here for species-specific activity table Ligand is labelled Ligand is radioactive Hs Full agonist 10.4 pKd
⤷ pKd 10.4 (Kd 4.2x10-11 M) α2β4
CP-601927 Small molecule or natural product Primary target of this compound Hs Partial agonist 8.9 pKi 8
⤷ pKi 8.9 (Ki 1.2x10-9 M) [8]
Description: Measured against α2β4 nAchRs- species not identified.
[3H]cytisine Small molecule or natural product Click here for species-specific activity table Ligand is labelled Ligand is radioactive Hs Full agonist - -
⤷
View species-specific agonist tables
Agonist Comments
The plant-derived compound cytisinicline behaves as a partial agonist at α4α2 nACh receptors (EC50 0.42 nM in α4α2-expressing K-177 cells [4].
Channel Blockers
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Use-dependent Value Parameter Concentration range (M) Voltage-dependent (mV) Reference
hexamethonium Small molecule or natural product Click here for species-specific activity table Hs - no - - - no
⤷
Not voltage dependent
mecamylamine Small molecule or natural product Approved drug Click here for species-specific activity table Hs - no - - - no
⤷
Not voltage dependent
Allosteric Modulators
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Concentration range (M) Voltage-dependent (mV) Reference
LY2087101 Small molecule or natural product Click here for species-specific activity table Hs Positive - - - no 3
⤷ [3]
Not voltage dependent
Tissue Distribution Click here for help
Brain:-
High levels of α2 subunit mRNA are expressed in the interpeduncular nucleus. Expression has also been detected in the dorsal and ventral tegmental nuclei in the hindbrain.
Expression level:  High
Species:  Mouse
Technique:  in situ hybridisation
References:  6-7
Brain:-
Radio-ligand binding studies in knockout mice provides evidence for expression of α2-containing nAChRs in interpeduncular nucleus and olfactory bulbs.
Species:  Mouse
Technique:  Radioligand binding
References:  13
Brain:-
High levels of α2 subunit mRNA are expressed in the interpeduncular nucleus. Expression has also been detected in some areas of the olfactory bulbs, hippocampal formation, amgydala and a few brainstem nuclei. Developmental changes in expression have been reported, with expression in the cortex and hippocampus reaching a peak at postnatal day 7.
Expression level:  High
Species:  Rat
Technique:  in situ hybridisation
References:  6,10-12
Tissue Distribution Comments
In situ hybridization of rhesus monkey tissue shows that α1 mRNA appears to be more widely expressed in primate brain than in rodent brain. And relatively intense hybridization was observed in several thalamic nuclei of the Macaca mulatta brain with a pattern closely resembling that seen for α4. Low levels of expression in the interpeduncular nucleus (the site of most intense expression in rodents) [5].
Physiological Consequences of Altering Gene Expression Click here for help
Nicotinic receptor α2 subunit knockout mice have reduced nicotine-induced modulation of long-term potentiation in the hippocampal CA1 region.
Species:  Mouse
Tissue:  in vivo
Technique:  Knockout (homologous recombination)
References:  9
Clinically-Relevant Mutations and Pathophysiology Click here for help
Disease:  Epilepsy, nocturnal frontal lobe 4, ENFL4
Synonyms: Autosomal dominant nocturnal frontal lobe epilepsy [Orphanet: ORPHA98784]
OMIM: 610353
Orphanet: ORPHA98784
References:  1
Click column headers to sort
Type Species Amino acid change Nucleotide change Description Reference
Missense Human I279N The amino acid substitution is located in the first transmembrane domain 1

References

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1. Aridon P, Marini C, Di Resta C, Brilli E, De Fusco M, Politi F, Parrini E, Manfredi I, Pisano T, Pruna D et al.. (2006) Increased sensitivity of the neuronal nicotinic receptor alpha 2 subunit causes familial epilepsy with nocturnal wandering and ictal fear. Am J Hum Genet, 79 (2): 342-50. [PMID:16826524]

2. 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]

3. Broad LM, Zwart R, Pearson KH, Lee M, Wallace L, McPhie GI, Emkey R, Hollinshead SP, Dell CP, Baker SR et al.. (2006) Identification and pharmacological profile of a new class of selective nicotinic acetylcholine receptor potentiators. J Pharmacol Exp Ther, 318 (3): 1108-17. [PMID:16738207]

4. Fitch RW, Kaneko Y, Klaperski P, Daly JW, Seitz G, Gündisch D. (2005) Halogenated and isosteric cytisine derivatives with increased affinity and functional activity at nicotinic acetylcholine receptors. Bioorg Med Chem Lett, 15 (4): 1221-4. [PMID:15686946]

5. 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]

6. Ishii K, Wong JK, Sumikawa K. (2005) Comparison of alpha2 nicotinic acetylcholine receptor subunit mRNA expression in the central nervous system of rats and mice. J Comp Neurol, 493 (2): 241-60. [PMID:16255031]

7. 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]

8. Mineur YS, Einstein EB, Seymour PA, Coe JW, O'neill BT, Rollema H, Picciotto MR. (2011) α4β2 nicotinic acetylcholine receptor partial agonists with low intrinsic efficacy have antidepressant-like properties. Behav Pharmacol, 22 (4): 291-9. [PMID:21566524]

9. Nakauchi S, Brennan RJ, Boulter J, Sumikawa K. (2007) Nicotine gates long-term potentiation in the hippocampal CA1 region via the activation of alpha2* nicotinic ACh receptors. Eur J Neurosci, 25 (9): 2666-81. [PMID:17466021]

10. Son JH, Winzer-Serhan UH. (2006) Postnatal expression of alpha2 nicotinic acetylcholine receptor subunit mRNA in developing cortex and hippocampus. J Chem Neuroanat, 32 (2-4): 179-90. [PMID:17046198]

11. 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]

12. Wada K, Ballivet M, Boulter J, Connolly J, Wada E, Deneris ES, Swanson LW, Heinemann S, Patrick J. (1988) Functional expression of a new pharmacological subtype of brain nicotinic acetylcholine receptor. Science, 240 (4850): 330-4. [PMID:2832952]

13. Whiteaker P, Wilking JA, Brown RW, Brennan RJ, Collins AC, Lindstrom JM, Boulter J. (2009) Pharmacological and immunochemical characterization of alpha2* nicotinic acetylcholine receptors (nAChRs) in mouse brain. Acta Pharmacol Sin, 30 (6): 795-804. [PMID:19498420]

14. Wood S, Schertzer M, Yaremko ML. (1995) Identification of the human neuronal nicotinic cholinergic alpha 2 receptor locus, (CHRNA2), within an 8p21 mapped locus, by sequence homology with rat DNA. Somat Cell Mol Genet, 21 (2): 147-50. [PMID:7570187]

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