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α2

Family: Nicotinic acetylcholine receptors

Contents:
Gene and Protein Information
Previous and Unofficial Names
Database Links
Tissue Distribution
Physiological Consequences of Altering Gene Expression
Clinically-Relevant Mutations and Pathophysiology
References
Gene and Protein Information
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human 4 529 8p21 CHRNA2 cholinergic receptor, nicotinic, alpha 2 (neuronal) 11
Mouse 4 512 14 D1 Chrna2 cholinergic receptor, nicotinic, alpha polypeptide 2 (neuronal) 2
Rat 4 511 15p12 Chrna2 cholinergic receptor, nicotinic, alpha 2 (neuronal) 9
Previous and Unofficial Names
cholinergic receptor, nicotinic, alpha polypeptide 2 (neuronal)
acetylcholine receptor, nicotinic, alpha 2 (neuronal)
ACHR
neuronal acetylcholine receptor subunit alpha-2
nicotinic acetylcholine receptor
Acra-2
Acra2
BC011490
Database Links
ChEMBL Target 171 (Hs), 10023 (Rn)
DrugBank Target 813 (Hs)
Ensembl ENSG00000120903 (Hs), ENSMUSG00000022041 (Mm), ENSRNOG00000017424 (Rn)
Entrez Gene 1135 (Hs), 110902 (Mm), 170945 (Rn)
GeneCards CHRNA2 (Hs)
GenitoUrinary Development Molecular Anatomy Project Chrna2 (Mm)
HomoloGene 20193 (Hs)
Human Protein Reference Database 00332 (Hs)
InterPro Q15822 (Hs), Q91X60 (Mm), P12389 (Rn)
KEGG Gene hsa:1135 (Hs), mmu:110902 (Mm), rno:170945 (Rn)
OMIM 118502 (Hs)
Orphanet Gene ORPHA159345 (Hs)
PharmGKB Gene PA26489 (Hs)
PhosphoSitePlus Q15822 (Hs), Q91X60 (Mm), P12389 (Rn)
Protein Ontology (PRO) PRO:000005455 (Hs)
RefSeq Nucleotide NM_000742 (Hs), NM_144803 (Mm), NM_133420 (Rn)
RefSeq Protein NP_000733 (Hs), NP_659052 (Mm), NP_596911 (Rn)
TreeFam ENSG00000120903 (Hs), ENSMUSG00000022041 (Mm), ENSRNOG00000017424 (Rn)
UniGene Hs. 558310 (Hs)
UniProt Q15822 (Hs), Q91X60 (Mm), P12389 (Rn)
Wikipedia α2
Nicotinic acetylcholine receptors
Search for 3D structures on the PDB
Search by keyword: Nicotinic acetylcholine receptors α2 Search by accession number: P12389, Q91X60, Q15822
Natural/Endogenous Ligand(s)
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)

Explore drug-target interactions for this set of compounds using iPHACE

Tissue Distribution
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:  4-5
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:  radio-ligand binding
References:  10
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:  4,7-9
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).[3]
Physiological Consequences of Altering Gene Expression
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:  6
Clinically-Relevant Mutations and Pathophysiology
Disease:  Familial sleep-related focal epilepsy
References:  1
Click column headers to sort
Type Species Molecular location Description Reference
Missense Human I279N mutation (located in the first transmembrane domain) 1
Disease:  Nocturnal frontal lobe epilepsy, type 4
OMIM:  610353
Orphanet:  98784
References: 
Mutations not determined

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. 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]

4. 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]

5. 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]

6. 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]

7. 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]

8. 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]

9. 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]

10. 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]

11. 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]

To cite this database page, please use the following:

Cecilia Gotti, Michael. J. Marks, Neil S. Millar, Susan Wonnacott.
Nicotinic acetylcholine receptors: α2. Last modified on 20/01/2012. Accessed on 19/05/2013. IUPHAR database (IUPHAR-DB), http://www.iuphar-db.org/DATABASE/ObjectDisplayForward?objectId=463.


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