Acetylcholine receptors at mature mammalian neuromuscular junctions are pentameric protein complexes composed of four subunits in the ratio of two alpha subunits to one beta, one epsilon, and one delta subunit. The acetylcholine receptor changes subunit composition shortly after birth when the epsilon subunit replaces the gamma subunit seen in embryonic receptors. Mutations in the epsilon subunit are associated with congenital myasthenic syndrome. [provided by RefSeq, Sep 2009]
Function:
After binding acetylcholine, the AChR responds by an extensive change in conformation that affects all subunits and leads to opening of an ion-conducting channel across the plasma membrane.
Subunit:
Pentamer of two alpha chains, and one each of the beta, delta, and gamma (in immature muscle) or epsilon (in mature muscle) chains.
Subcellular Location:
Cell junction; synapse; postsynaptic cell membrane. Cell membrane.
DISEASE:
Note=The muscle AChR is the major target antigen in the autoimmune disease myasthenia gravis. Myasthenia gravis is characterized by sporadic muscular fatigability and weakness, occurring chiefly in muscles innervated by cranial nerves, and characteristically improved by cholinesterase-inhibiting drugs.
Defects in CHRNE are a cause of congenital myasthenic syndrome slow-channel type (SCCMS) [MIM:601462]. SCCMS is the most common congenital myasthenic syndrome. Congenital myasthenic syndromes are characterized by muscle weakness affecting the axial and limb muscles (with hypotonia in early-onset forms), the ocular muscles (leading to ptosis and ophthalmoplegia), and the facial and bulbar musculature (affecting sucking and swallowing, and leading to dysphonia). The symptoms fluctuate and worsen with physical effort. SCCMS is caused by kinetic abnormalities of the AChR, resulting in prolonged endplate currents and prolonged AChR channel opening episodes.
Defects in CHRNE are a cause of congenital myasthenic syndrome fast-channel type (FCCMS) [MIM:608930]. FCCMS is a congenital myasthenic syndrome characterized by kinetic abnormalities of the AChR. In most cases, FCCMS is due to mutations that decrease activity of the AChR by slowing the rate of opening of the receptor channel, speeding the rate of closure of the channel, or decreasing the number of openings of the channel during ACh occupancy. The result is failure to achieve threshold depolarization of the endplate and consequent failure to fire an action potential.
Defects in CHRNE are a cause of congenital myasthenic syndrome with acetylcholine receptor deficiency (CMS-ACHRD) [MIM:608931]. CMS-ACHRD is a postsynaptic congenital myasthenic syndrome. Mutations underlying AChR deficiency cause a 'loss of function' and show recessive inheritance.
Similarity:
Belongs to the ligand-gated ion channel (TC 1.A.9) family.
Acetylcholine receptor (TC 1.A.9.1) subfamily.
Epsilon/CHRNE sub-subfamily.
SWISS:
Q04844
Gene ID:
1145
Database links:
Entrez Gene: 1145 Human
Entrez Gene: 281688 Cow
Entrez Gene: 101137825 Gorilla
Entrez Gene: 100146223 Horse
Entrez Gene: 11448 Mouse
Entrez Gene: 29422 Rat
Entrez Gene: 710301 Rhesus monkey
GenBank: NP_033733.1 Mouse
Omim: 100725 Human
SwissProt: P02715 Cow
SwissProt: Q04844 Human
SwissProt: P20782 Mouse
SwissProt: P09660 Rat
Unigene: 654535 Human
Unigene: 4196 Mouse
Unigene: 10301 Rat
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