Neuronal acetylcholine receptor subunit alpha-4
Also known as: CHRNA4, NACRA4
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. CHRNA4 forms heteropentameric neuronal acetylcholine receptors with CHRNB2 and CHRNB4, as well as CHRNA5 and CHRNB3 as accesory subunits. Is the most abundant nAChR subtype expressed in the central nervous system. Found in two major stoichiometric forms,(CHRNA4)3:(CHRNB2)2 and (CHRNA4)2:(CHRNB2)3, the two stoichiometric forms differ in their unitary conductance, calcium permeability, ACh sensitivity and potentiation by divalent cation. Involved in the modulation of calcium-dependent signaling pathways, influences the release of neurotransmitters, including dopamine, glutamate and GABA (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 · 12
- 2LLY NMR
- 5KXI X-ray 3.94A
- 6CNJ EM 3.40A
- 6CNK EM 3.70A
- 6UR8 EM 3.71A
- 6USF EM 3.87A
- 8SSZ EM 2.64A
- 8ST0 EM 2.40A
- 8ST1 EM 3.41A
- 8ST2 EM 2.94A
- 8ST3 EM 2.93A
- 8ST4 EM 2.35A
A predicted model is available from AlphaFold.
Gene Ontology · 40
- GO:0005892 acetylcholine-gated channel complex
- GO:0034703 cation channel complex
- GO:0030425 dendrite
- GO:0009897 external side of plasma membrane
- GO:0016020 membrane
- GO:0043005 neuron projection
- GO:0043025 neuronal cell body
- GO:0098878 neurotransmitter receptor complex
- GO:0005886 plasma membrane
- 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:0140658 ATP-dependent chromatin remodeler activity
- GO:0015276 ligand-gated monoatomic ion channel activity
- GO:0095500 acetylcholine receptor signaling pathway
- GO:0001508 action potential
- GO:0042113 B cell activation
- GO:0035095 behavioral response to nicotine
- GO:0006816 calcium ion transport
- GO:0007268 chemical synaptic transmission
- GO:0050890 cognition
- GO:0006281 DNA repair
- GO:0060080 inhibitory postsynaptic potential
- GO:0051899 membrane depolarization
- GO:0034220 monoatomic ion transmembrane transport
- GO:0006811 monoatomic ion transport
- GO:0050877 nervous system process
- GO:0007274 neuromuscular synaptic transmission
- GO:0099171 presynaptic modulation of chemical synaptic transmission
- GO:0014059 regulation of dopamine secretion
- GO:0042391 regulation of membrane potential
- GO:0001666 response to hypoxia
- GO:0035094 response to nicotine
- GO:0006979 response to oxidative stress
- GO:0019233 sensory perception of pain
- GO:0007165 signal transduction
- GO:0007271 synaptic transmission, cholinergic
Disease associations
- autosomal dominant nocturnal frontal lobe epilepsy 1 MONDO:0010899
Drugs targeting this protein · 15
- VARENICLINE partial agonist
- ALTINICLINE agonist
- POZANICLINE partial agonist
- DIANICLINE partial agonist
- ISPRONICLINE partial agonist
- DEXMECAMYLAMINE antagonist
- TEBANICLINE TOSYLATE agonist
- AZD1446 agonist
- SOFINICLINE agonist
- NICOTINE agonist
- CP-601927 partial agonist
- SIMPINICLINE agonist
- CYTISINICLINE partial agonist
- TC-2216 antagonist
- VARENICLINE TARTRATE agonist
Related proteins · sequence + function similarity
- Neuronal acetylcholine receptor subunit alpha-4 1.00
- Neuronal acetylcholine receptor subunit alpha-4 0.97
- Neuronal acetylcholine receptor subunit alpha-4 0.97
- Neuronal acetylcholine receptor subunit alpha-4 0.97
- Neuronal acetylcholine receptor subunit alpha-2 0.95
- Neuronal acetylcholine receptor subunit alpha-2 0.95
- Neuronal acetylcholine receptor subunit alpha-2 0.92
- Neuronal acetylcholine receptor subunit alpha-2 0.91
- Neuronal acetylcholine receptor subunit alpha-2 0.91
- Neuronal acetylcholine receptor subunit alpha-4 0.90
- Neuronal acetylcholine receptor subunit alpha-3 0.90
- Neuronal acetylcholine receptor subunit beta-2 0.89
Co-cited proteins · studied together in the literature
- Neuronal acetylcholine receptor subunit beta-2 12 shared papers
- Neuronal acetylcholine receptor subunit alpha-6 3 shared papers
- Neuronal acetylcholine receptor subunit beta-3 3 shared papers
- Neuronal acetylcholine receptor subunit beta-4 5 shared papers
- Neuronal acetylcholine receptor subunit alpha-5 4 shared papers
- Neuronal acetylcholine receptor subunit alpha-3 5 shared papers
- Neuronal acetylcholine receptor subunit alpha-7 4 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
- Protein RIC-3 1 shared papers
- Ly6/PLAUR domain-containing protein 6 1 shared papers
Literature · 19 cited papers
- Structural bases for stoichiometry-selective calcium potentiation of a neuronal nicotinic receptor. Br. J. Pharmacol. · 2024
- Structural principles of distinct assemblies of the human alpha4beta2 nicotinic receptor. Nature · 2018
- X-ray structure of the human alpha4beta2 nicotinic receptor. Nature · 2016
- Functional interaction between Lypd6 and nicotinic acetylcholine receptors. J. Neurochem. · 2016
- NMR structures of the transmembrane domains of the alpha4beta2 nAChR. Biochim. Biophys. Acta · 2012
- Acetylcholine receptor (AChR) alpha5 subunit variant associated with risk for nicotine dependence and lung cancer reduces (alpha4beta2)(2)alpha5 AChR function. Mol. Pharmacol. · 2011
- Ca2+ permeability of the (alpha4)3(beta2)2 stoichiometry greatly exceeds that of (alpha4)2(beta2)3 human acetylcholine receptors. Mol. Pharmacol. · 2007
- Beta3 subunits promote expression and nicotine-induced up-regulation of human nicotinic alpha6* nicotinic acetylcholine receptors expressed in transfected cell lines. Mol. Pharmacol. · 2006
- RIC-3 enhances functional expression of multiple nicotinic acetylcholine receptor subtypes in mammalian cells. Mol. Pharmacol. · 2005
- The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. · 2004
- A Korean kindred with autosomal dominant nocturnal frontal lobe epilepsy and mental retardation. Arch. Neurol. · 2003
- Alternate stoichiometries of alpha4beta2 nicotinic acetylcholine receptors. Mol. Pharmacol. · 2003
- … and 7 more in the literature graph