nicotinic acetylcholine receptor α1 subunit

Target id: 462

Nomenclature: nicotinic acetylcholine receptor α1 subunit

Family: Nicotinic acetylcholine receptors

Annotation status:  image of a green circle Annotated and expert reviewed. Please contact us if you can help with updates.  » Email us

Gene and Protein Information
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human 4 482 2q24-q32 CHRNA1 cholinergic receptor, nicotinic, alpha 1 (muscle) 10
Mouse 4 457 2 C3 Chrna1 cholinergic receptor, nicotinic, alpha polypeptide 1 (muscle) 7
Rat 4 457 3q23 Chrna1 cholinergic receptor, nicotinic, alpha 1 (muscle) 14
Previous and Unofficial Names
acetylcholine receptor subunit alpha
Achr-1
Database Links
ChEMBL Target
DrugBank Target
Ensembl Gene
Entrez Gene
GeneCards
GenitoUrinary Development Molecular Anatomy Project
HomoloGene
Human Protein Reference Database
InterPro
KEGG Gene
NeXtProt
OMIM
Orphanet
PharmGKB Gene
PhosphoSitePlus
Protein Ontology (PRO)
RefSeq Nucleotide
RefSeq Protein
TreeFam
UniGene Hs.
UniProtKB
Wikipedia
Functional Characteristics
(α1)2βγδ: PCa/PNa = 0.16 - 0.2, Pf = 2.1 – 2.9%; (α1)2βδε: PCa/PNa = 0.65 – 1.38, Pf = 4.1 – 7.2%
Natural/Endogenous Ligands
acetylcholine
Commonly used antagonists (Human)
(α1)2β1γδ and (α1)2β1δε: α-bungarotoxin > pancuronium > vecuronium > rocuronium > tubocurarine (IC50 = 43 - 82 nM)

Download all structure-activity data for this target as a CSV file

Agonists
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Affinity Units Reference
succinylcholine Hs Full agonist - -
selective for (α1)2β1γδ
Antagonists
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Affinity Units Reference
α-bungarotoxin Hs Antagonist - -
[125I]α-bungarotoxin Hs Antagonist - -
[3H]α-bungarotoxin Hs Antagonist - -
α-conotoxin GI Hs Antagonist - -
waglerin-1 Hs Antagonist - -
selective for (α1)2β1δε
α-conotoxin MI Hs Antagonist - -
pancuronium Hs Antagonist - -
Channel Blockers
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Use-dependent Affinity Units Concentration range (M) Voltage-dependent (mV) Reference
gallamine Hs - no ~6.0 pIC50 - no
pIC50 ~6.0 (IC50 ~1x10-6 M) (α1)2β1γδ and (α1)2β1δε
Not voltage dependent
mecamylamine Hs - no ~5.8 pIC50 - no
pIC50 ~5.8 (IC50 ~1.5x10-6 M) (α1)2β1δε
Not voltage dependent
Tissue Distribution Comments
In vertebrates α1-subunit mRNA is generally expressed in skeletal muscle
Physiological Consequences of Altering Gene Expression
Homozygous knockout mice die at birth. Kyphosis and carpoptosis phenotypes are apparent in embryonic mice. Increased motor axon branching and expanded innervation were also seen. Spontaneous miniature and nerve-evoked endplate potentials were absent in muscle.
Species:  Mouse
Tissue:  in vivo
Technique:  Gene knockout
References:  1
Clinically-Relevant Mutations and Pathophysiology
Disease:  Multiple pterygium syndrome, lethal type; LMPS
Description: A fetal akinesia deformation sequence (FADS) disorder
Synonyms: Lethal multiple pterygium syndrome [Orphanet: ORPHA33108]
OMIM: 253290
Orphanet: ORPHA33108
Comments: 
References:  8
Click column headers to sort
Type Species Amino acid change Nucleotide change Description Reference
Frameshift: Duplication Human H24RfsX19 c.117-133 dup17 Homozygous duplication of 17 base pairs in in exon 2 of the gene causing a frameshift and premature stop codon. 8
Missense Human R234L 761G>T 8
Disease:  Myasthenia gravis
Disease Ontology: DOID:437
OMIM: 254200
Orphanet: ORPHA589
Role: 
References:  6
Disease:  Myasthenic syndrome, congenital, 1A, slow-channel; CMS1A
Synonyms: Congenital myasthenic syndrome [Orphanet: ORPHA590] [Disease Ontology: DOID:3635]
Postsynaptic congenital myasthenic syndromes [Orphanet: ORPHA98913]
Disease Ontology: DOID:3635
OMIM: 601462
Orphanet: ORPHA98913, ORPHA590
References:  4-5
Click column headers to sort
Type Species Amino acid change Nucleotide change Description Reference
Missense Human G153S 12
Missense Human V156M 2
Missense Human N217K 3
Missense Human V249F 9
Missense Human T254I 2
Missense Human S269I 2
Missense Human C418W 11
Disease:  Myasthenic syndrome, congenital, 1B, fast-channel; CMS1B
Synonyms: Congenital myasthenic syndrome [Disease Ontology: DOID:3635] [Orphanet: ORPHA590]
Postsynaptic congenital myasthenic syndromes [Orphanet: ORPHA98913]
Disease Ontology: DOID:3635
OMIM: 608930
Orphanet: ORPHA98913, ORPHA590
References:  4-5
Click column headers to sort
Type Species Amino acid change Nucleotide change Description Reference
Missense Human F233V 13
Missense Human V285I 13
General Comments
The human α1 subunit exists as two variants that arise from alternative splicing. The long variant is tabulated above.

References

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1. An MC, Lin W, Yang J, Dominguez B, Padgett D, Sugiura Y, Aryal P, Gould TW, Oppenheim RW, Hester ME et al.. (2010) Acetylcholine negatively regulates development of the neuromuscular junction through distinct cellular mechanisms. Proc. Natl. Acad. Sci. U.S.A.107 (23): 10702-7. [PMID:20498043]

2. Croxen R, Newland C, Beeson D, Oosterhuis H, Chauplannaz G, Vincent A, Newsom-Davis J. (1997) Mutations in different functional domains of the human muscle acetylcholine receptor alpha subunit in patients with the slow-channel congenital myasthenic syndrome. Hum. Mol. Genet.6 (5): 767-74. [PMID:9158151]

3. Engel AG, Ohno K, Milone M, Wang HL, Nakano S, Bouzat C, Pruitt 2nd JN, Hutchinson DO, Brengman JM, Bren N et al.. (1996) New mutations in acetylcholine receptor subunit genes reveal heterogeneity in the slow-channel congenital myasthenic syndrome. Hum. Mol. Genet.5 (9): 1217-27. [PMID:8872460]

4. Engel AG, Ohno K, Sine SM. (2003) Sleuthing molecular targets for neurological diseases at the neuromuscular junction. Nat. Rev. Neurosci.4 (5): 339-52. [PMID:12728262]

5. Engel AG, Shen XM, Selcen D, Sine SM. (2010) What have we learned from the congenital myasthenic syndromes. J. Mol. Neurosci.40 (1-2): 143-53. [PMID:19688192]

6. Lindstrom JM. (2000) Acetylcholine receptors and myasthenia. Muscle Nerve23 (4): 453-77. [PMID:10716755]

7. Merlie JP, Sebbane R, Gardner S, Lindstrom J. (1983) cDNA clone for the alpha subunit of the acetylcholine receptor from the mouse muscle cell line BC3H-1. Proc. Natl. Acad. Sci. U.S.A.80 (12): 3845-9. [PMID:6344089]

8. Michalk A, Stricker S, Becker J, Rupps R, Pantzar T, Miertus J, Botta G, Naretto VG, Janetzki C, Yaqoob N et al.. (2008) Acetylcholine receptor pathway mutations explain various fetal akinesia deformation sequence disorders. Am. J. Hum. Genet.82 (2): 464-76. [PMID:18252226]

9. Milone M, Wang HL, Ohno K, Fukudome T, Pruitt JN, Bren N, Sine SM, Engel AG. (1997) Slow-channel myasthenic syndrome caused by enhanced activation, desensitization, and agonist binding affinity attributable to mutation in the M2 domain of the acetylcholine receptor alpha subunit. J. Neurosci.17 (15): 5651-65. [PMID:9221765]

10. Noda M, Furutani Y, Takahashi H, Toyosato M, Tanabe T, Shimizu S, Kikyotani S, Kayano T, Hirose T, Inayama S. (1983) Cloning and sequence analysis of calf cDNA and human genomic DNA encoding alpha-subunit precursor of muscle acetylcholine receptor. Nature305 (5937): 818-23. [PMID:6688857]

11. Shen XM, Deymeer F, Sine SM, Engel AG. (2006) Slow-channel mutation in acetylcholine receptor alphaM4 domain and its efficient knockdown. Ann. Neurol.60 (1): 128-36. [PMID:16685696]

12. Sine SM, Ohno K, Bouzat C, Auerbach A, Milone M, Pruitt JN, Engel AG. (1995) Mutation of the acetylcholine receptor alpha subunit causes a slow-channel myasthenic syndrome by enhancing agonist binding affinity. Neuron15 (1): 229-39. [PMID:7619526]

13. Wang HL, Milone M, Ohno K, Shen XM, Tsujino A, Batocchi AP, Tonali P, Brengman J, Engel AG, Sine SM. (1999) Acetylcholine receptor M3 domain: stereochemical and volume contributions to channel gating. Nat. Neurosci.2 (3): 226-33. [PMID:10195214]

14. Witzemann V, Stein E, Barg B, Konno T, Koenen M, Kues W, Criado M, Hofmann M, Sakmann B. (1990) Primary structure and functional expression of the alpha-, beta-, gamma-, delta- and epsilon-subunits of the acetylcholine receptor from rat muscle. Eur. J. Biochem.194 (2): 437-48. [PMID:1702709]

How to cite this page

Cecilia Gotti, Michael. J. Marks, Neil S. Millar, Susan Wonnacott.
Nicotinic acetylcholine receptors: nicotinic acetylcholine receptor α1 subunit. Last modified on 25/05/2015. Accessed on 05/09/2015. IUPHAR/BPS Guide to PHARMACOLOGY, http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=462.