Neuronal acetylcholine receptor subunit alpha-3
Also known as: CHRNA3, NACHRA3
Function
Component of neuronal acetylcholine receptors (nAChRs) that function as pentameric, ligand-gated cation channels with high calcium permeability among other activities. nAChRs are excitatory neurotrasnmitter receptors formed by a collection of nAChR subunits known to mediate synaptic transmission in the nervous system and the neuromuscular junction. Each nAchR subunit confers differential attributes to channel properties, including activation, deactivation and desensitization kinetics, pH sensitivity, cation permeability, and binding to allosteric modulators. CHRNA3 forms heteropentameric neuronal acetylcholine receptors with CHRNB2 and CHRNB4, with CHRNA5, and CHRNB3 as accesory subunits. CHRNA3:CHRNB4 being predominant in neurons of the autonomic ganglia, it is known as ganglionic nicotinic receptor. CHRNA3:CHRNB4 or CHRNA3:CHRNA5:CHRNB4 play also an important role in the habenulo-interpeduncular tract, modulating the mesolimbic dopamine system and affecting reward circuits and addiction (By similarity). Hypothalamic CHRNA3:CHRNB4 nAChR activation by nicotine leads to activation of POMC neurons and a decrease in food intake (By similarity). Also expressed in the urothelium where it modulates reflex bladder activity by increasing intracellular calcium through extracellular influx and basal ATP release (By similarity).
Classification
- Family (Pfam)
- PF02931 Neur_chan_LBD, PF02932 Neur_chan_memb
- InterPro
- Neur_chan_lig-bd, Neur_chan_lig-bd_sf, Neur_channel, Neuro-gated_channel_TM_sf, Neuro_actylchol_rec, Neurotrans-gated_channel_TM, Neurotransmitter_ion_chnl_CS, Nicotinic_acetylcholine_rcpt
- Functional cluster
- Cytochrome P450 & Heme Enzymes
Experimental structures · PDB · 5
A predicted model is available from AlphaFold.
Gene Ontology · 38
- GO:0005892 acetylcholine-gated channel complex
- GO:0034703 cation channel complex
- GO:0030425 dendrite
- GO:0005783 endoplasmic reticulum
- GO:0005794 Golgi apparatus
- GO:0016020 membrane
- GO:0043005 neuron projection
- GO:0043025 neuronal cell body
- GO:0098878 neurotransmitter receptor complex
- GO:0005886 plasma membrane
- GO:0044853 plasma membrane raft
- GO:0045211 postsynaptic membrane
- GO:0042734 presynaptic membrane
- GO:0045202 synapse
- GO:0042166 acetylcholine binding
- GO:0015464 acetylcholine receptor activity
- GO:0022848 acetylcholine-gated monoatomic cation-selective channel activity
- GO:0015276 ligand-gated monoatomic ion channel activity
- GO:0095500 acetylcholine receptor signaling pathway
- GO:0035095 behavioral response to nicotine
- GO:0060079 excitatory postsynaptic potential
- GO:0007626 locomotory behavior
- GO:0051899 membrane depolarization
- GO:0034220 monoatomic ion transmembrane transport
- GO:0006811 monoatomic ion transport
- GO:0007399 nervous system development
- GO:0007274 neuromuscular synaptic transmission
- GO:0099171 presynaptic modulation of chemical synaptic transmission
- GO:0014056 regulation of acetylcholine secretion, neurotransmission
- GO:0032098 regulation of appetite
- GO:0048814 regulation of dendrite morphogenesis
- GO:0042391 regulation of membrane potential
- GO:0006940 regulation of smooth muscle contraction
- GO:1905144 response to acetylcholine
- GO:0035094 response to nicotine
- GO:0007165 signal transduction
- GO:0060084 synaptic transmission involved in micturition
- GO:0007271 synaptic transmission, cholinergic
Disease associations
- urinary bladder, atony of MONDO:0008630
- OMIM:612052 RAW:OMIM_612052
Drugs targeting this protein · 5
- MECAMYLAMINE HYDROCHLORIDE negative allosteric modulator
- TRIMETHAPHAN CAMSYLATE antagonist
- PENTOLINIUM TARTRATE antagonist
- LARAZOTIDE ACETATE partial agonist
- SIMPINICLINE agonist
Related proteins · sequence + function similarity
- Neuronal acetylcholine receptor subunit alpha-3 0.99
- Neuronal acetylcholine receptor subunit alpha-3 0.99
- Neuronal acetylcholine receptor subunit alpha-3 0.98
- Neuronal acetylcholine receptor subunit alpha-3 0.97
- Neuronal acetylcholine receptor subunit alpha-6 0.96
- Neuronal acetylcholine receptor subunit alpha-6 0.96
- Neuronal acetylcholine receptor subunit alpha-6 0.96
- Acetylcholine receptor subunit alpha 0.96
- Neuronal acetylcholine receptor subunit alpha-6 0.96
- Neuronal acetylcholine receptor subunit alpha-6 0.96
- Neuronal acetylcholine receptor subunit alpha-2 0.96
- Acetylcholine receptor subunit alpha 0.96
Co-cited proteins · studied together in the literature
- Neuronal acetylcholine receptor subunit alpha-5 8 shared papers
- Neuronal acetylcholine receptor subunit beta-4 10 shared papers
- Neuronal acetylcholine receptor subunit beta-2 9 shared papers
- Neuronal acetylcholine receptor subunit beta-3 3 shared papers
- Neuronal acetylcholine receptor subunit alpha-4 5 shared papers
- Neuronal acetylcholine receptor subunit alpha-7 5 shared papers
- Neuronal acetylcholine receptor subunit alpha-6 2 shared papers
- Ly6/PLAUR domain-containing protein 6 1 shared papers
- Neuronal acetylcholine receptor subunit alpha-2 1 shared papers
- Neuronal acetylcholine receptor subunit alpha-7 1 shared papers
- Neuronal acetylcholine receptor subunit alpha-3 2 shared papers
- Alpha-conotoxin ImII 1 shared papers
Literature · 21 cited papers
- CAKUT and autonomic dysfunction caused by acetylcholine receptor mutations. Am. J. Hum. Genet. · 2019
- Agonist Selectivity and Ion Permeation in the alpha3beta4 Ganglionic Nicotinic Receptor. Neuron · 2019
- Functional interaction between Lypd6 and nicotinic acetylcholine receptors. J. Neurochem. · 2016
- UBXN2A regulates nicotinic receptor degradation by modulating the E3 ligase activity of CHIP. Biochem. Pharmacol. · 2015
- Acetylcholine receptor (AChR) alpha5 subunit variant associated with risk for nicotine dependence and lung cancer reduces (alpha4beta2)(2)alpha5 AChR function. Mol. Pharmacol. · 2011
- A variant associated with nicotine dependence, lung cancer and peripheral arterial disease. Nature · 2008
- A susceptibility locus for lung cancer maps to nicotinic acetylcholine receptor subunit genes on 15q25. Nature · 2008
- Genomics: when the smoke clears. Nature · 2008
- Genome-wide association scan of tag SNPs identifies a susceptibility locus for lung cancer at 15q25.1. Nat. Genet. · 2008
- Analysis of the DNA sequence and duplication history of human chromosome 15. Nature · 2006
- RIC-3 enhances functional expression of multiple nicotinic acetylcholine receptor subtypes in mammalian cells. Mol. Pharmacol. · 2005
- Alpha-conotoxins ImI and ImII target distinct regions of the human alpha7 nicotinic acetylcholine receptor and distinguish human nicotinic receptor subtypes. Biochemistry · 2004
- … and 9 more in the literature graph