CHRNA1 cdna clone
CHRNA1 cDNA Clone
NCBI and Uniprot Product Information
NCBI Description
The muscle acetylcholine receptor consiststs of 5 subunits of 4 different types: 2 alpha subunits and 1 each of the beta, gamma, and delta subunits. This gene encodes an alpha subunit that plays a role in acetlycholine binding/channel gating. Alternatively spliced transcript variants encoding different isoforms have been identified. [provided by RefSeq, Nov 2012]
Uniprot Description
nAChRA1: 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. Defects in CHRNA1 are a cause of multiple pterygium syndrome lethal type (MUPSL). Multiple pterygia are found infrequently in children with arthrogryposis and in fetuses with fetal akinesia syndrome. In lethal multiple pterygium syndrome there is intrauterine growth retardation, multiple pterygia, and flexion contractures causing severe arthrogryposis and fetal akinesia. Subcutaneous edema can be severe, causing fetal hydrops with cystic hygroma and lung hypoplasia. Oligohydramnios and facial anomalies are frequent. The alpha subunit is the main focus for antibody binding in 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 CHRNA1 are a cause of congenital myasthenic syndrome slow-channel type (SCCMS). 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 CHRNA1 are a cause of congenital myasthenic syndrome fast-channel type (FCCMS). 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. Belongs to the ligand-gated ion channel (TC 1.A.9) family. Acetylcholine receptor (TC 1.A.9.1) subfamily. Alpha- 1/CHRNA1 sub-subfamily. 2 isoforms of the human protein are produced by alternative splicing.
Protein type: Membrane protein, integral; Membrane protein, multi-pass; Receptor, misc.; Channel, ligand-gated; Channel, cation
Chromosomal Location of Human Ortholog: 2q31.1
Cellular Component: cell surface; neuromuscular junction; nicotinic acetylcholine-gated receptor-channel complex; plasma membrane
Molecular Function: acetylcholine binding; acetylcholine receptor activity; ion channel activity; ligand-gated ion channel activity; nicotinic acetylcholine-activated cation-selective channel activity
Biological Process: generation of action potential; muscle maintenance; musculoskeletal movement; neuromuscular junction development; neuromuscular process; neuromuscular synaptic transmission; regulation of membrane potential; response to nicotine; signal transduction; skeletal muscle contraction; skeletal muscle growth; synaptic transmission, cholinergic; transport
Disease: Multiple Pterygium Syndrome, Lethal Type; Myasthenic Syndrome, Congenital, Fast-channel; Myasthenic Syndrome, Congenital, Slow-channel
