nicotinic acetylcholine receptor ε subunit

Target id: 477

Nomenclature: nicotinic acetylcholine receptor ε 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 4 493 17p13-p12 CHRNE cholinergic receptor, nicotinic, epsilon (muscle) 1
Mouse 4 493 11 B3 Chrne cholinergic receptor, nicotinic, epsilon polypeptide 2
Rat 4 494 10q24 Chrne cholinergic receptor, nicotinic, epsilon (muscle) 16
Previous and Unofficial Names
ACHRE
Acre
Database Links
ChEMBL 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
Natural/Endogenous Ligands
acetylcholine
Tissue Distribution Comments
The ε-subunit mRNA is expressed in vertebrate skeletal muscle. Whereas expression of the γ-subunit predominates in embryonic muscle, expression of the ε-subunit occurs during early neonatal development and persists in adult muscle.
Physiological Consequences of Altering Gene Expression
In knockout mice, loss of the ε-subunit is partially compensated by expression of the γ-subunit, but results in premature death 2 to 3 months after birth. Mice display impaired neuromuscular transmission, progressive muscle weakness and atrophy.
Species:  Mouse
Tissue:  in vivo
Technique:  Gene knockout
References:  10,15
Mice with an ε-subunit null mutation associated with the human AChR deficiency syndrome die between 10 and 14 weeks after birth. However, mice with the ε null mutation but which also consitutively express the human γ-subunit survive into adult life.
Species:  Mouse
Tissue:  in vivo
Technique:  Knock-in
References:  3
Clinically-Relevant Mutations and Pathophysiology
Disease:  Myasthenic syndrome, congenital, 4A, slow-channel; CMS4A
Synonyms: Congenital myasthenic syndrome [Disease Ontology: DOID:3635] [Orphanet: ORPHA590]
Postsynaptic congenital myasthenic syndromes [Orphanet: ORPHA98913]
Disease Ontology: DOID:3635
OMIM: 605809
Orphanet: ORPHA590, ORPHA98913
References:  7-9
Click column headers to sort
Type Species Amino acid change Nucleotide change Description Reference
Missense Human L78P 4
Missense Human R217L 4
Missense Human L221F 4
Missense Human T264P 11
Missense Human L269F 6
Disease:  Myasthenic syndrome, congenital, 4B, fast-channel; CMS4B
Synonyms: Congenital myasthenic syndrome [Disease Ontology: DOID:3635] [Orphanet: ORPHA590]
Postsynaptic congenital myasthenic syndromes [Orphanet: ORPHA98913]
Disease Ontology: DOID:3635
OMIM: 616324
Orphanet: ORPHA590, ORPHA98913
Role: 
References:  7-9
Click column headers to sort
Type Species Amino acid change Nucleotide change Description Reference
Missense Human W55R 13
Missense Human P121L 12
Missense Human A411P 14
Disease:  Myasthenic syndrome, congenital, 4C, associated with acetylcholine receptor deficiency; CMS4C
Synonyms: Congenital myasthenic syndrome [Disease Ontology: DOID:3635] [Orphanet: ORPHA590]
Postsynaptic congenital myasthenic syndromes [Orphanet: ORPHA98913]
Disease Ontology: DOID:3635
OMIM: 608931
Orphanet: ORPHA98913, ORPHA590
References:  5
Click column headers to sort
Type Species Amino acid change Nucleotide change Description Reference
Frameshift: Insertion Human 1101insT Insertion of thymine after nucleotide 1101 directly generates a nonsense codon leading to a truncated protein. 5
Frameshift: Insertion Human 1293insG Insertion of guanine at nucleotide position 1293 results in three missense codons followed by a nonsense codon and truncated protein 5

References

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1. Beeson D, Brydson M, Betty M, Jeremiah S, Povey S, Vincent A, Newsom-Davis J. (1993) Primary structure of the human muscle acetylcholine receptor. cDNA cloning of the gamma and epsilon subunits. Eur. J. Biochem.215 (2): 229-38. [PMID:7688301]

2. Buonanno A, Mudd J, Merlie JP. (1989) Isolation and characterization of the beta and epsilon subunit genes of mouse muscle acetylcholine receptor. J. Biol. Chem.264 (13): 7611-6. [PMID:2708381]

3. Cossins J, Webster R, Maxwell S, Burke G, Vincent A, Beeson D. (2004) A mouse model of AChR deficiency syndrome with a phenotype reflecting the human condition. Hum. Mol. Genet.13 (23): 2947-57. [PMID:15471888]

4. Croxen R, Hatton C, Shelley C, Brydson M, Chauplannaz G, Oosterhuis H, Vincent A, Newsom-Davis J, Colquhoun D, Beeson D. (2002) Recessive inheritance and variable penetrance of slow-channel congenital myasthenic syndromes. Neurology59 (2): 162-8. [PMID:12141316]

5. Engel AG, Ohno K, Bouzat C, Sine SM, Griggs RC. (1996) End-plate acetylcholine receptor deficiency due to nonsense mutations in the epsilon subunit. Ann. Neurol.40 (5): 810-7. [PMID:8957026]

6. 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]

7. Engel AG, Ohno K, Sine SM. (2003) Congenital myasthenic syndromes: A diverse array of molecular targets. J. Neurocytol.32 (5-8): 1017-37. [PMID:15034283]

8. 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]

9. 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]

10. Missias AC, Mudd J, Cunningham JM, Steinbach JH, Merlie JP, Sanes JR. (1997) Deficient development and maintenance of postsynaptic specializations in mutant mice lacking an 'adult' acetylcholine receptor subunit. Development124 (24): 5075-86. [PMID:9362465]

11. Ohno K, Hutchinson DO, Milone M, Brengman JM, Bouzat C, Sine SM, Engel AG. (1995) Congenital myasthenic syndrome caused by prolonged acetylcholine receptor channel openings due to a mutation in the M2 domain of the epsilon subunit. Proc. Natl. Acad. Sci. U.S.A.92 (3): 758-62. [PMID:7531341]

12. Ohno K, Wang HL, Milone M, Bren N, Brengman JM, Nakano S, Quiram P, Pruitt JN, Sine SM, Engel AG. (1996) Congenital myasthenic syndrome caused by decreased agonist binding affinity due to a mutation in the acetylcholine receptor epsilon subunit. Neuron17 (1): 157-70. [PMID:8755487]

13. Shen XM, Brengman JM, Edvardson S, Sine SM, Engel AG. (2012) Highly fatal fast-channel syndrome caused by AChR ε subunit mutation at the agonist binding site. Neurology79 (5): 449-54. [PMID:22592360]

14. Wang HL, Ohno K, Milone M, Brengman JM, Evoli A, Batocchi AP, Middleton LT, Christodoulou K, Engel AG, Sine SM. (2000) Fundamental gating mechanism of nicotinic receptor channel revealed by mutation causing a congenital myasthenic syndrome. J. Gen. Physiol.116 (3): 449-62. [PMID:10962020]

15. Witzemann V, Schwarz H, Koenen M, Berberich C, Villarroel A, Wernig A, Brenner HR, Sakmann B. (1996) Acetylcholine receptor epsilon-subunit deletion causes muscle weakness and atrophy in juvenile and adult mice. Proc. Natl. Acad. Sci. U.S.A.93 (23): 13286-91. [PMID:8917583]

16. 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 ε subunit. Last modified on 25/05/2015. Accessed on 04/09/2015. IUPHAR/BPS Guide to PHARMACOLOGY, http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=477.