{"results":[{"entryType":"UniProtKB reviewed (Swiss-Prot)","primaryAccession":"P36544","secondaryAccessions":["A8K7Q4","B4DFS0","Q15826","Q8IUZ4","Q96RH2","Q99555","Q9BXH0"],"uniProtkbId":"ACHA7_HUMAN","entryAudit":{"firstPublicDate":"1994-06-01","lastAnnotationUpdateDate":"2026-09-02","lastSequenceUpdateDate":"1997-11-01","entryVersion":236,"sequenceVersion":5},"annotationScore":5.0,"organism":{"scientificName":"Homo sapiens","commonName":"Human","taxonId":9606,"lineage":["Eukaryota","Metazoa","Chordata","Craniata","Vertebrata","Euteleostomi","Mammalia","Eutheria","Euarchontoglires","Primates","Haplorrhini","Catarrhini","Hominidae","Homo"]},"proteinExistence":"1: Evidence at protein level","proteinDescription":{"recommendedName":{"fullName":{"value":"Neuronal acetylcholine receptor subunit alpha-7"},"shortNames":[{"value":"nAChR7"}]},"alternativeNames":[{"fullName":{"value":"Nicotinic acetylcholine receptor subunit alpha-7"}}],"flag":"Precursor"},"genes":[{"geneName":{"evidences":[{"evidenceCode":"ECO:0000312","source":"HGNC","id":"HGNC:1960"}],"value":"CHRNA7"},"synonyms":[{"value":"NACHRA7"}]}],"comments":[{"texts":[{"evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"Q05941"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"12508119"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"15609996"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"16968406"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"17709503"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"25259522"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"31560909"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"33239400"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"33735609"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"38382524"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"8145738"},{"evidenceCode":"ECO:0000305","source":"PubMed","id":"18723036"}],"value":"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)"}],"commentType":"FUNCTION"},{"commentType":"CATALYTIC ACTIVITY","reaction":{"name":"Ca(2+)(in) = Ca(2+)(out)","reactionCrossReferences":[{"database":"Rhea","id":"RHEA:29671"},{"database":"ChEBI","id":"CHEBI:29108"}],"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"33735609"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"8145738"}]}},{"commentType":"CATALYTIC ACTIVITY","reaction":{"name":"K(+)(in) = K(+)(out)","reactionCrossReferences":[{"database":"Rhea","id":"RHEA:29463"},{"database":"ChEBI","id":"CHEBI:29103"}],"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"33735609"}]}},{"commentType":"CATALYTIC ACTIVITY","reaction":{"name":"Na(+)(in) = Na(+)(out)","reactionCrossReferences":[{"database":"Rhea","id":"RHEA:34963"},{"database":"ChEBI","id":"CHEBI:29101"}],"evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"P02709"}]}},{"commentType":"CATALYTIC ACTIVITY","reaction":{"name":"choline(out) = choline(in)","reactionCrossReferences":[{"database":"Rhea","id":"RHEA:32751"},{"database":"ChEBI","id":"CHEBI:15354"}],"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"33735609"}]}},{"commentType":"CATALYTIC ACTIVITY","reaction":{"name":"NH4(+)(in) = NH4(+)(out)","reactionCrossReferences":[{"database":"Rhea","id":"RHEA:28747"},{"database":"ChEBI","id":"CHEBI:28938"}],"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"33735609"}]}},{"commentType":"CATALYTIC ACTIVITY","reaction":{"name":"L-arginine(in) = L-arginine(out)","reactionCrossReferences":[{"database":"Rhea","id":"RHEA:32143"},{"database":"ChEBI","id":"CHEBI:32682"}],"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"33735609"}]}},{"commentType":"CATALYTIC ACTIVITY","reaction":{"name":"guanidine(out) = guanidine(in)","reactionCrossReferences":[{"database":"Rhea","id":"RHEA:73883"},{"database":"ChEBI","id":"CHEBI:30087"}],"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"33735609"}]}},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"12508119"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"15609996"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"16968406"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"31560909"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"33239400"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"33735609"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"38161283"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"38382524"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"8145738"}],"value":"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)"}],"commentType":"ACTIVITY REGULATION"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"P54131"},{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"Q05941"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"15504725"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"15609996"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"16120769"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"27344019"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"32783947"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"33239400"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"33735609"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"38161283"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"38382524"}],"value":"Homopentamer (PubMed:33735609, PubMed:38382524). Can also form heteropentamers with CHRNB2, mainly found in basal forebrain cholinergic neurons (PubMed:33239400, PubMed:38161283). Interacts with RIC3; which is required for proper folding and assembly (PubMed:15504725, PubMed:16120769). Interacts with LYPD6 (PubMed:27344019). Interacts with CANX (PubMed:32783947)"}],"commentType":"SUBUNIT"},{"commentType":"INTERACTION","interactions":[{"interactantOne":{"uniProtKBAccession":"P36544","intActId":"EBI-79333"},"interactantTwo":{"uniProtKBAccession":"P05067","geneName":"APP","intActId":"EBI-77613"},"numberOfExperiments":4,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"P36544","intActId":"EBI-79333"},"interactantTwo":{"uniProtKBAccession":"P05067","geneName":"APP","chainId":"PRO_0000000092","intActId":"EBI-821758"},"numberOfExperiments":7,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"P36544","intActId":"EBI-79333"},"interactantTwo":{"uniProtKBAccession":"Q9NSI6-4","geneName":"BRWD1","intActId":"EBI-10693038"},"numberOfExperiments":3,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"P36544","intActId":"EBI-79333"},"interactantTwo":{"uniProtKBAccession":"Q494W8","geneName":"CHRFAM7A","intActId":"EBI-20798208"},"numberOfExperiments":3,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"P36544","intActId":"EBI-79333"},"interactantTwo":{"uniProtKBAccession":"Q9UBU7","geneName":"DBF4","intActId":"EBI-372690"},"numberOfExperiments":3,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"P36544","intActId":"EBI-79333"},"interactantTwo":{"uniProtKBAccession":"Q8N5J2-3","geneName":"MINDY1","intActId":"EBI-12382151"},"numberOfExperiments":3,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"P36544","intActId":"EBI-79333"},"interactantTwo":{"uniProtKBAccession":"Q09028","geneName":"RBBP4","intActId":"EBI-620823"},"numberOfExperiments":3,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"P36544","intActId":"EBI-79333"},"interactantTwo":{"uniProtKBAccession":"P55000","geneName":"SLURP1","intActId":"EBI-8830896"},"numberOfExperiments":2,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"P36544","intActId":"EBI-79333"},"interactantTwo":{"uniProtKBAccession":"Q13573","geneName":"SNW1","intActId":"EBI-632715"},"numberOfExperiments":3,"organismDiffer":false}]},{"commentType":"SUBCELLULAR LOCATION","note":{"texts":[{"evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"Q05941"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"27789755"}],"value":"TMEM35A/NACHO promotes its trafficking to the cell membrane (PubMed:27789755). RIC3 promotes its trafficking to the cell membrane (By similarity)"}]},"subcellularLocations":[{"location":{"evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"Q05941"}],"value":"Postsynaptic cell membrane","id":"SL-0219"},"topology":{"evidences":[{"evidenceCode":"ECO:0000255"}],"value":"Multi-pass membrane protein","id":"SL-9909"}},{"location":{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"27789755"}],"value":"Cell membrane","id":"SL-0039"},"topology":{"evidences":[{"evidenceCode":"ECO:0000255"}],"value":"Multi-pass membrane protein","id":"SL-9909"}}]},{"commentType":"ALTERNATIVE PRODUCTS","events":["Alternative splicing"],"isoforms":[{"name":{"value":"1"},"isoformIds":["P36544-1"],"isoformSequenceStatus":"Displayed"},{"name":{"value":"2"},"isoformIds":["P36544-2"],"sequenceIds":["VSP_043019"],"isoformSequenceStatus":"Described"},{"name":{"value":"3"},"isoformIds":["P36544-3"],"sequenceIds":["VSP_058107","VSP_058108"],"isoformSequenceStatus":"Described"}]},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"12508119"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"8145738"}],"value":"Expressed in neuronal cells (PubMed:8145738). Expressed in macrophages (at protein level) (PubMed:12508119)"}],"commentType":"TISSUE SPECIFICITY"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"P49582"}],"value":"Glycosylations at Asn-46, Asn-90 and Asn-133 are essential for TMEM35A/NACHO-mediated proper subunit assembly and trafficking to the cell membrane"}],"commentType":"PTM"},{"commentType":"MASS SPECTROMETRY","method":"MALDI","molWeight":54157.68,"molWeightError":0.0,"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"11840567"}]},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000305"}],"value":"May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay"}],"commentType":"MISCELLANEOUS","molecule":"Isoform 3"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000305"}],"value":"Belongs to the ligand-gated ion channel (TC 1.A.9) family. Acetylcholine receptor (TC 1.A.9.1) subfamily. Alpha-7/CHRNA7 sub-subfamily"}],"commentType":"SIMILARITY"},{"commentType":"SEQUENCE CAUTION","sequenceCautionType":"Erroneous translation","sequence":"AAH37571.1","note":"Wrong choice of frame.","evidences":[{"evidenceCode":"ECO:0000305"}]}],"features":[{"type":"Signal","location":{"start":{"value":1,"modifier":"EXACT"},"end":{"value":22,"modifier":"EXACT"}},"description":"","evidences":[{"evidenceCode":"ECO:0000255"}]},{"type":"Chain","location":{"start":{"value":23,"modifier":"EXACT"},"end":{"value":502,"modifier":"EXACT"}},"description":"Neuronal acetylcholine receptor subunit alpha-7","featureId":"PRO_0000000366"},{"type":"Topological 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