{"results":[{"entryType":"UniProtKB reviewed (Swiss-Prot)","primaryAccession":"P32297","secondaryAccessions":["Q15823","Q4KMN8","Q86U77","Q96RH3","Q99553","Q9BQ93","Q9BRR4"],"uniProtkbId":"ACHA3_HUMAN","entryAudit":{"firstPublicDate":"1993-10-01","lastAnnotationUpdateDate":"2026-09-02","lastSequenceUpdateDate":"2009-07-28","entryVersion":234,"sequenceVersion":4},"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-3"}},"flag":"Precursor"},"genes":[{"geneName":{"evidences":[{"evidenceCode":"ECO:0000312","source":"HGNC","id":"HGNC:1957"}],"value":"CHRNA3"},"synonyms":[{"value":"NACHRA3"}]}],"comments":[{"texts":[{"evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"P04757"},{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"Q8R4G9"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"20881005"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"31488329"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"31708116"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"8663494"}],"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:31488329, PubMed:31708116). CHRNA3 forms heteropentameric neuronal acetylcholine receptors with CHRNB2 and CHRNB4, with CHRNA5, and CHRNB3 as accesory subunits (PubMed:20881005, PubMed:8663494). CHRNA3:CHRNB4 being predominant in neurons of the autonomic ganglia, it is known as ganglionic nicotinic receptor (PubMed:31488329). 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)"}],"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":"20881005"}]}},{"commentType":"CATALYTIC ACTIVITY","reaction":{"name":"K(+)(in) = K(+)(out)","reactionCrossReferences":[{"database":"Rhea","id":"RHEA:29463"},{"database":"ChEBI","id":"CHEBI:29103"}],"evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"P02709"}]}},{"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":"P43681"}]}},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"P04757"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"11118490"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"15609996"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"20881005"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"31488329"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"8906617"}],"value":"Activated by a myriad of ligands such as acetylcholine, cytisine, nicotine, choline and epibatidine (PubMed:11118490, PubMed:20881005, PubMed:31488329, PubMed:8906617). The heteropentamer CHRNA3:CHRNB2 activity is blocked by alpha-conotoxins ImI, ImII, PnIA, GID and MII (By similarity). The heteropentamer CHRNA3:CHRNB4 activity is blocked by the alpha-conotoxin ImI and AuIB (PubMed:15609996)"}],"commentType":"ACTIVITY REGULATION"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"11118490"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"15609996"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"16120769"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"20881005"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"26265139"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"27344019"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"31488329"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"8663494"}],"value":"Neuronal AChR is composed of two different types of subunits: alpha and beta. CHRNA3/Alpha-3 subunit can be combined to CHRNA5/alpha-5, CHRNB2/beta-2 CHRNB3/beta-3 or CHRNB4/beta-4 to give rise to functional receptors (PubMed:20881005, PubMed:31488329, PubMed:8663494). Forms stoichiometries such as (CHRNA3)2:(CHRNB4)3 or (CHRNA3:CHRNB4)2:CHRNB3 (PubMed:11118490). Part of a complex composed of STUB1/CHIP, VCP/p97, CHRNA3, and UBXN2A that modulates the ubiquitination and endoplasmic reticulum-associated degradation (ERAD) of CHRNA3 (PubMed:26265139). Within the complex UBXN2A acts as a scaffold protein required for the interaction of CHRNA3 with VCP/p97, this interaction also inhibits CHRNA3 ubiquitination by STUB1/CHIP and subsequently ERAD (PubMed:26265139). Interacts with UBXN2A (via SEP domain), the interaction is required for the interaction of CHRNA3 in the STUB1:VCP:UBXN2A complex (PubMed:26265139). Interacts with RIC3; which is required for proper folding and assembly (PubMed:16120769). Interacts with LYPD6 (PubMed:27344019)"}],"commentType":"SUBUNIT"},{"commentType":"SUBCELLULAR LOCATION","note":{"texts":[{"evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"P04757"}],"value":"Interaction with UBXN2A/UBXD4 promotes translocation to the plasma membrane"}]},"subcellularLocations":[{"location":{"evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"P04757"}],"value":"Synaptic cell membrane","id":"SL-0531"},"topology":{"evidences":[{"evidenceCode":"ECO:0000255"}],"value":"Multi-pass membrane protein","id":"SL-9909"}},{"location":{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"31708116"}],"value":"Cell membrane","id":"SL-0039"},"topology":{"evidences":[{"evidenceCode":"ECO:0000255"}],"value":"Multi-pass membrane protein","id":"SL-9909"}},{"location":{"evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"P04757"}],"value":"Endoplasmic reticulum","id":"SL-0095"}},{"location":{"evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"P04757"}],"value":"Golgi apparatus","id":"SL-0132"}}]},{"commentType":"ALTERNATIVE PRODUCTS","events":["Alternative splicing"],"isoforms":[{"name":{"value":"2"},"isoformIds":["P32297-2"],"isoformSequenceStatus":"Displayed"},{"name":{"value":"1"},"isoformIds":["P32297-1"],"sequenceIds":["VSP_037750"],"isoformSequenceStatus":"Described"},{"name":{"value":"3"},"isoformIds":["P32297-3"],"sequenceIds":["VSP_037751"],"isoformSequenceStatus":"Described"}]},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"P04757"}],"value":"Ubiquitinated; by STUB1/CHIP and thereafter degraded by the 26S proteosome complex"}],"commentType":"PTM"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"18385676"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"18385720"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"18385738"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"18385739"}],"value":"Genetic variations in CHRNA3 have been associated with susceptibility to smoking-related behavioral traits and lung cancer, contributing to the smoking quantitative trait locus 3 (SQTL3) [MIM:612052]"}],"commentType":"POLYMORPHISM"},{"commentType":"DISEASE","disease":{"diseaseId":"Bladder dysfunction, autonomic, with impaired pupillary reflex and secondary CAKUT","diseaseAccession":"DI-05743","acronym":"BAIPRCK","description":"An autosomal recessive disease characterized by impaired innervation and autonomic dysfunction of the urinary bladder, hydronephrosis, vesicoureteral reflux, small kidneys, recurrent urinary tract infections, and progressive renal insufficiency. 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