Neuronal acetylcholine receptor subunit alpha-7
Also known as: CHRNA7, NACHRA7
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. CHRNA7 forms homopentameric neuronal acetylcholine receptors abundantly expressed in the central nervous system, characterized by fast desensitization and high calcium permeability. Also forms heteropentamers with CHRNB2, mainly expressed in basal forebrain cholinergic neurons. Involved in the modulation of calcium-dependent signaling pathways and influences the release of neurotransmitters, including dopamine, glutamate and GABA. Also expressed in non-neuronal cells such as immune cells like lymphocytes, monocytes and macrophages. In T cells, activation induces metabotropic signaling that results in an increase of intracellular Ca2+ concentrations, independent of ionotropic receptor functions. In macrophages, required for acetylcholine-mediated inhibition of TNF and other inflammatory cytokine release. Once activated by acetylcholine, nicotine or other agonists, selectively inhibits production of pro-inflammatory cytokines while leaving anti-inflammatory cytokines undisturbed. Stimulates the cholinergic anti-inflammatory pathway, controlling inflammation by inhibiting NFKB nuclear translocation and activating the JAK2-STAT3 pathway, independently of ion channel activity. Also expressed in the urothelium where it modulates reflex bladder activity by increasing intracellular calcium through internal stores and decreasing 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 · 46
- 2MAW NMR
- 5AFH X-ray 2.40A
- 5AFJ X-ray 2.20A
- 5AFK X-ray 2.38A
- 5AFL X-ray 2.38A
- 5AFM X-ray 2.85A
- 5AFN X-ray 2.15A
- 7EKI EM 3.18A
- 7EKP EM 2.85A
- 7EKT EM 3.02A
- 7KOO EM 3.00A
- 7KOQ EM 3.60A
- … and 34 more
A predicted model is available from AlphaFold.
Gene Ontology · 58
- GO:0005892 acetylcholine-gated channel complex
- GO:0030425 dendrite
- GO:0005789 endoplasmic reticulum membrane
- GO:0016020 membrane
- GO:0043005 neuron projection
- GO:0005886 plasma membrane
- GO:0044853 plasma membrane raft
- GO:0098794 postsynapse
- GO:0045211 postsynaptic membrane
- GO:0045202 synapse
- GO:0042166 acetylcholine binding
- GO:0015464 acetylcholine receptor activity
- GO:0022848 acetylcholine-gated monoatomic cation-selective channel activity
- GO:0001540 amyloid-beta binding
- GO:0005262 calcium channel activity
- GO:0017081 chloride channel regulator activity
- GO:0005216 monoatomic ion channel activity
- GO:0042803 protein homodimerization activity
- GO:0015643 toxic substance binding
- GO:0004888 transmembrane signaling receptor activity
- GO:0095500 acetylcholine receptor signaling pathway
- GO:0006816 calcium ion transport
- GO:0007268 chemical synaptic transmission
- GO:0050890 cognition
- GO:0140059 dendrite arborization
- GO:0097061 dendritic spine organization
- GO:0060079 excitatory postsynaptic potential
- GO:0006874 intracellular calcium ion homeostasis
- GO:0007611 learning or memory
- GO:0007613 memory
- GO:0098815 modulation of excitatory postsynaptic potential
- GO:0034220 monoatomic ion transmembrane transport
- GO:0006811 monoatomic ion transport
- GO:1902430 negative regulation of amyloid-beta formation
- GO:0043124 negative regulation of canonical NF-kappaB signal transduction
- GO:1900016 negative regulation of cytokine production involved in inflammatory response
- GO:0032720 negative regulation of tumor necrosis factor production
- GO:1902004 positive regulation of amyloid-beta formation
- GO:0045766 positive regulation of angiogenesis
- GO:0008284 positive regulation of cell population proliferation
- GO:0070374 positive regulation of ERK1 and ERK2 cascade
- GO:2000463 positive regulation of excitatory postsynaptic potential
- GO:1900273 positive regulation of long-term synaptic potentiation
- GO:0043410 positive regulation of MAPK cascade
- GO:0051247 positive regulation of protein metabolic process
- GO:1905906 regulation of amyloid fibril formation
- GO:1902991 regulation of amyloid precursor protein catabolic process
- GO:0042391 regulation of membrane potential
- GO:1905144 response to acetylcholine
- GO:1904645 response to amyloid-beta
- GO:0001666 response to hypoxia
- GO:0035094 response to nicotine
- GO:0050893 sensory processing
- GO:0007614 short-term memory
- GO:0007165 signal transduction
- GO:0050808 synapse organization
- GO:0060084 synaptic transmission involved in micturition
- GO:0007271 synaptic transmission, cholinergic
Drugs targeting this protein · 13
- BRADANICLINE agonist
- GTS-21 agonist
- PHA-543613 agonist
- AZD0328 agonist
- ABT-107 agonist
- ENCENICLINE partial agonist
- ABT-126 agonist
- AQW051 partial agonist
- JNJ-39393406 positive allosteric modulator
- AVL-3288 positive allosteric modulator
- FACINICLINE HYDROCHLORIDE partial agonist
- TC-6987 agonist
- SSR180711 partial agonist
Related proteins · sequence + function similarity
- Neuronal acetylcholine receptor subunit alpha-7 1.00
- Neuronal acetylcholine receptor subunit alpha-7 1.00
- Neuronal acetylcholine receptor subunit alpha-7 0.99
- Neuronal acetylcholine receptor subunit alpha-7 0.99
- Neuronal acetylcholine receptor subunit alpha-7 0.98
- CHRNA7-FAM7A fusion protein 0.94
- Neuronal acetylcholine receptor subunit beta-2 0.91
- Neuronal acetylcholine receptor subunit beta-4 0.90
- Neuronal acetylcholine receptor subunit alpha-3 0.90
- Neuronal acetylcholine receptor subunit beta-2 0.90
- Neuronal acetylcholine receptor subunit alpha-2 0.89
- Neuronal acetylcholine receptor subunit beta-4 0.89
Co-cited proteins · studied together in the literature
- Neuronal acetylcholine receptor subunit alpha-7 4 shared papers
- CHRNA7-FAM7A fusion protein 1 shared papers
- Neuronal acetylcholine receptor subunit alpha-7 1 shared papers
- Speedy protein E11 1 shared papers
- Neuronal acetylcholine receptor subunit beta-2 7 shared papers
- Neuronal acetylcholine receptor subunit alpha-7 2 shared papers
- Protein RIC-3 2 shared papers
- Novel acetylcholine receptor chaperone 2 shared papers
- Neuronal acetylcholine receptor subunit alpha-2 2 shared papers
- Neuronal acetylcholine receptor subunit beta-4 5 shared papers
- Neuronal acetylcholine receptor subunit alpha-3 5 shared papers
- Neuronal acetylcholine receptor subunit alpha-4 4 shared papers
Literature · 26 cited papers
- Structural mechanisms of alpha7 nicotinic receptor allosteric modulation and activation. Cell · 2024
- Analogs of alpha-conotoxin PnIC selectively inhibit alpha7beta2- over alpha7-only subtype nicotinic acetylcholine receptors via a novel allosteric mechanism. FASEB J. · 2024
- Structure and gating mechanism of the alpha7 nicotinic acetylcholine receptor. Cell · 2021
- Implications of Oligomeric Amyloid-Beta (oAbeta42) Signaling through alpha7beta2-Nicotinic Acetylcholine Receptors (nAChRs) on Basal Forebrain Cholinergic Neuronal Intrinsic Excitability and Cognitive Decline. J. Neurosci. · 2021
- NACHO Engages N-Glycosylation ER Chaperone Pathways for alpha7 Nicotinic Receptor Assembly. Cell Rep. · 2020
- Flavonoids as positive allosteric modulators of alpha7 nicotinic receptors. Neuropharmacology · 2019
- A Genome-Wide Arrayed cDNA Screen to Identify Functional Modulators of alpha7 Nicotinic Acetylcholine Receptors. SLAS Discovery · 2017
- Functional interaction between Lypd6 and nicotinic acetylcholine receptors. J. Neurochem. · 2016
- A new IRAK-M-mediated mechanism implicated in the anti-inflammatory effect of nicotine via alpha7 nicotinic receptors in human macrophages. PLoS ONE · 2014
- Diversity of vertebrate nicotinic acetylcholine receptors. Neuropharmacology · 2009
- T cells express alpha7-nicotinic acetylcholine receptor subunits that require a functional TCR and leukocyte-specific protein tyrosine kinase for nicotine-induced Ca2+ response. J. Immunol. · 2007
- Nicotine inhibits the production of proinflammatory mediators in human monocytes by suppression of I-kappaB phosphorylation and nuclear factor-kappaB transcriptional activity through nicotinic acetylcholine receptor alpha7. Clin. Exp. Immunol. · 2006
- … and 14 more in the literature graph