P36544
uniprot
P36544
canonical
activity_regulation
ACTIVITY REGULATION: Activated by a myriad of ligands such as acetylcholine, cytisine, nicotine, choline and epibatidine (PubMed:12508119, PubMed:16968406, PubMed:33735609, PubMed:38382524, PubMed:8145738). Oligomeric amyloid-beta protein 42 activates specifially CHRNA7:CHRNB2 nAchRs (PubMed:33239400). Activity is modulated by positive allosteric modulators (PAMs), such as flavonoids, with a wide range of chemical diversity, pharmacological sensitivity and efficacy (PubMed:31560909, PubMed:38382524). AChR activity is inhibited by the antagonists alpha-conotoxons RgIA, ImI and ImII, small disulfide-constrained peptides from cone snails (PubMed:15609996). Alpha-conotoxin PnIC selectively inhibits CHRNA7:CHRNB2 over CHRNA7 homopentamer (PubMed:38161283). {ECO:0000269|PubMed:12508119, ECO:0000269|PubMed:15609996, ECO:0000269|PubMed:16968406, ECO:0000269|PubMed:31560909, ECO:0000269|PubMed:33239400, ECO:0000269|PubMed:33735609, ECO:0000269|PubMed:38161283, ECO:0000269|PubMed:38382524, ECO:0000269|PubMed:8145738}.
uniprot
proteins
amino_acid_sequence
MRCSPGGVWLALAASLLHVSLQGEFQRKLYKELVKNYNPLERPVANDSQPLTVYFSLSLLQIMDVDEKNQVLTTNIWLQMSWTDHYLQWNVSEYPGVKTVRFPDGQIWKPDILLYNSADERFDATFHTNVLVNSSGHCQYLPPGIFKSSCYIDVRWFPFDVQHCKLKFGSWSYGGWSLDLQMQEADISGYIPNGEWDLVGIPGKRSERFYECCKEPYPDVTFTVTMRRRTLYYGLNLLIPCVLISALALLVFLLPADSGEKISLGITVLLSLTVFMLLVAEIMPATSDSVPLIAQYFASTMIIVGLSVVVTVIVLQYHHHDPDGGKMPKWTRVILLNWCAWFLRMKRPGEDKVRPACQHKQRRCSLASVEMSAVAPPPASNGNLLYIGFRGLDGVHCVPTPDSGVVCGRMACSPTHDEHLLHGGQPPEGDPDLAKILEEVRYIANRFRCQDESEAVCSEWKFAACVVDRLCLMAFSVFTIICTIGILMSAPNFVEAVSKDFA
uniprot
proteins
function
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 (PubMed:15609996, PubMed:33735609, PubMed:8145738). CHRNA7 forms homopentameric neuronal acetylcholine receptors abundantly expressed in the central nervous system, characterized by fast desensitization and high calcium permeability (PubMed:31560909, PubMed:33735609, PubMed:38382524, PubMed:8145738). 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 (PubMed:33239400). Also expressed in non-neuronal cells such as immune cells like lymphocytes, monocytes and macrophages (PubMed:12508119, PubMed:16968406, PubMed:25259522). In T cells, activation induces metabotropic signaling that results in an increase of intracellular Ca2+ concentrations, independent of ionotropic receptor functions (PubMed:17709503). In macrophages, required for acetylcholine-mediated inhibition of TNF and other inflammatory cytokine release (PubMed:12508119). Once activated by acetylcholine, nicotine or other agonists, selectively inhibits production of pro-inflammatory cytokines while leaving anti-inflammatory cytokines undisturbed (PubMed:12508119, PubMed:25259522). Stimulates the cholinergic anti-inflammatory pathway, controlling inflammation by inhibiting NFKB nuclear translocation and activating the JAK2-STAT3 pathway, independently of ion channel activity (PubMed:16968406, PubMed:25259522). 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). {ECO:0000250|UniProtKB:Q05941, ECO:0000269|PubMed:12508119, ECO:0000269|PubMed:15609996, ECO:0000269|PubMed:16968406, ECO:0000269|PubMed:17709503, ECO:0000269|PubMed:25259522, ECO:0000269|PubMed:31560909, ECO:0000269|PubMed:33239400, ECO:0000269|PubMed:33735609, ECO:0000269|PubMed:38382524, ECO:0000269|PubMed:8145738, ECO:0000305|PubMed:18723036}.
uniprot
proteins
mass_dalton
56449
uniprot
proteins
mutagenesis
MUTAGEN 120; /note="E->A: Decreases permeability to Ca(2+). No effect on permeability to K(+)."; /evidence="ECO:0000269|PubMed:33735609"; MUTAGEN 139; /note="Q->S: 115-fold more potently inhibited by the alpha-conotoxin ImI; but no change in inhibition by the alpha-conotoxin ImII."; /evidence="ECO:0000269|PubMed:15609996"; MUTAGEN 156; /note="W->A: No effect on ligand-gated cation channel activity."; /evidence="ECO:0000269|PubMed:33735609"; MUTAGEN 227; /note="R->A: No effect on ligand-gated cation channel activity."; /evidence="ECO:0000269|PubMed:33735609"; MUTAGEN 490; /note="Missing: Loss of ligand-gated cation channel activity."; /evidence="ECO:0000269|PubMed:33735609"; MUTAGEN 491; /note="P->A: Loss of ligand-gated cation channel activity."; /evidence="ECO:0000269|PubMed:33735609"; MUTAGEN 500; /note="D->A: No effect on ligand-gated cation channel activity."; /evidence="ECO:0000269|PubMed:33735609
uniprot
proteins
post_translational_modification
PTM: Glycosylations at Asn-46, Asn-90 and Asn-133 are essential for TMEM35A/NACHO-mediated proper subunit assembly and trafficking to the cell membrane. {ECO:0000250|UniProtKB:P49582}.
uniprot
proteins
protein_family
Acetylcholine receptor (TC 1.A.9.1) subfamily
uniprot
proteins
protein_family
Alpha-7/CHRNA7 sub-subfamily
uniprot
proteins
protein_family
Ligand-gated ion channel (TC 1.A.9) family
uniprot
proteins
pubmed
11829490
uniprot
proteins
pubmed
11840567
uniprot
proteins
pubmed
12508119
uniprot
proteins
pubmed
14702039
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
15504725
uniprot
proteins
pubmed
15609996
uniprot
proteins
pubmed
16120769
uniprot
proteins
pubmed
16572171
uniprot
proteins
pubmed
16968406
uniprot
proteins
pubmed
17709503
uniprot
proteins
pubmed
18723036
uniprot
proteins
pubmed
25259522
uniprot
proteins
pubmed
27344019
uniprot
proteins
pubmed
27789755
uniprot
proteins
pubmed
31560909
uniprot
proteins
pubmed
32783947
uniprot
proteins
pubmed
33239400
uniprot
proteins
pubmed
33735609
uniprot
proteins
pubmed
38161283
uniprot
proteins
pubmed
38382524
uniprot
proteins
pubmed
8145738
uniprot
proteins
pubmed
8188270
uniprot
proteins
pubmed
8906617
uniprot
proteins
pubmed
9009220
uniprot
proteins
pubmed
9782083
uniprot
proteins
sequence_length
502
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Postsynaptic cell membrane {ECO:0000250|UniProtKB:Q05941}; Multi-pass membrane protein {ECO:0000255}. Cell membrane {ECO:0000269|PubMed:27789755}; Multi-pass membrane protein {ECO:0000255}. Note=TMEM35A/NACHO promotes its trafficking to the cell membrane (PubMed:27789755). RIC3 promotes its trafficking to the cell membrane (By similarity). {ECO:0000250|UniProtKB:Q05941, ECO:0000269|PubMed:27789755}.
uniprot
proteins
transmembrane_region
TRANSMEM 234..254; /note="Helical"; /evidence="ECO:0000269|PubMed:33735609, ECO:0007744|PDB:7KOO"; TRANSMEM 259..279; /note="Helical"; /evidence="ECO:0000269|PubMed:33735609, ECO:0007744|PDB:7KOO"; TRANSMEM 292..315; /note="Helical"; /evidence="ECO:0000269|PubMed:33735609, ECO:0007744|PDB:7KOO"; TRANSMEM 467..489; /note="Helical"; /evidence="ECO:0000269|PubMed:33735609, ECO:0007744|PDB:7KOO
uniprot
proteins