ID   ACHA4_HUMAN             Reviewed;         627 AA.
AC   P43681; Q4JGR7; Q4VAQ5; Q4VAQ6;
DT   01-NOV-1995, integrated into UniProtKB/Swiss-Prot.
DT   01-FEB-1996, sequence version 2.
DT   27-MAR-2024, entry version 225.
DE   RecName: Full=Neuronal acetylcholine receptor subunit alpha-4;
DE   Flags: Precursor;
GN   Name=CHRNA4; Synonyms=NACRA4;
OS   Homo sapiens (Human).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC   Homo.
OX   NCBI_TaxID=9606;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RC   TISSUE=Brain;
RX   PubMed=7721089; DOI=10.1016/0378-1119(94)00914-e;
RA   Monteggia L.M., Gopalakrishnan M., Touma E., Idler K.B., Nash N.,
RA   Arneric S.P., Sullivan J.P., Giordano T.;
RT   "Cloning and transient expression of genes encoding the human alpha-4 and
RT   beta-2 neuronal nicotinic acetylcholine receptor (nAChR) subunits.";
RL   Gene 155:189-193(1995).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX   PubMed=8833159; DOI=10.1006/geno.1996.0119;
RA   Steinlein O.K., Weiland S., Stood J., Propping P.;
RT   "Exon-intron structure of the human neuronal nicotinic acetylcholine
RT   receptor alpha 4 subunit (CHRNA4).";
RL   Genomics 32:289-294(1996).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RC   TISSUE=Hippocampus;
RX   PubMed=8906617; DOI=10.1007/bf02736842;
RA   Elliott K.J., Ellis S.B., Berckhan K.J., Urrutia A., Chavez-Noriega L.E.,
RA   Johnson E.C., Velicelebi G., Harpold M.M.;
RT   "Comparative structure of human neuronal alpha 2-alpha 7 and beta 2-beta 4
RT   nicotinic acetylcholine receptor subunits and functional expression of the
RT   alpha 2, alpha 3, alpha 4, alpha 7, beta 2, and beta 4 subunits.";
RL   J. Mol. Neurosci. 7:217-228(1996).
RN   [4]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RX   PubMed=9009220; DOI=10.1016/s0014-5793(96)01383-x;
RA   Groot Kormelink P.J., Luyten W.H.M.L.;
RT   "Cloning and sequence of full-length cDNAs encoding the human neuronal
RT   nicotinic acetylcholine receptor (nAChR) subunits beta3 and beta4 and
RT   expression of seven nAChR subunits in the human neuroblastoma cell line SH-
RT   SY5Y and/or IMR-32.";
RL   FEBS Lett. 400:309-314(1997).
RN   [5]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS GLY-387 AND LEU-517.
RG   NIEHS SNPs program;
RL   Submitted (JUN-2005) to the EMBL/GenBank/DDBJ databases.
RN   [6]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX   PubMed=11780052; DOI=10.1038/414865a;
RA   Deloukas P., Matthews L.H., Ashurst J.L., Burton J., Gilbert J.G.R.,
RA   Jones M., Stavrides G., Almeida J.P., Babbage A.K., Bagguley C.L.,
RA   Bailey J., Barlow K.F., Bates K.N., Beard L.M., Beare D.M., Beasley O.P.,
RA   Bird C.P., Blakey S.E., Bridgeman A.M., Brown A.J., Buck D., Burrill W.D.,
RA   Butler A.P., Carder C., Carter N.P., Chapman J.C., Clamp M., Clark G.,
RA   Clark L.N., Clark S.Y., Clee C.M., Clegg S., Cobley V.E., Collier R.E.,
RA   Connor R.E., Corby N.R., Coulson A., Coville G.J., Deadman R., Dhami P.D.,
RA   Dunn M., Ellington A.G., Frankland J.A., Fraser A., French L., Garner P.,
RA   Grafham D.V., Griffiths C., Griffiths M.N.D., Gwilliam R., Hall R.E.,
RA   Hammond S., Harley J.L., Heath P.D., Ho S., Holden J.L., Howden P.J.,
RA   Huckle E., Hunt A.R., Hunt S.E., Jekosch K., Johnson C.M., Johnson D.,
RA   Kay M.P., Kimberley A.M., King A., Knights A., Laird G.K., Lawlor S.,
RA   Lehvaeslaiho M.H., Leversha M.A., Lloyd C., Lloyd D.M., Lovell J.D.,
RA   Marsh V.L., Martin S.L., McConnachie L.J., McLay K., McMurray A.A.,
RA   Milne S.A., Mistry D., Moore M.J.F., Mullikin J.C., Nickerson T.,
RA   Oliver K., Parker A., Patel R., Pearce T.A.V., Peck A.I.,
RA   Phillimore B.J.C.T., Prathalingam S.R., Plumb R.W., Ramsay H., Rice C.M.,
RA   Ross M.T., Scott C.E., Sehra H.K., Shownkeen R., Sims S., Skuce C.D.,
RA   Smith M.L., Soderlund C., Steward C.A., Sulston J.E., Swann R.M.,
RA   Sycamore N., Taylor R., Tee L., Thomas D.W., Thorpe A., Tracey A.,
RA   Tromans A.C., Vaudin M., Wall M., Wallis J.M., Whitehead S.L.,
RA   Whittaker P., Willey D.L., Williams L., Williams S.A., Wilming L.,
RA   Wray P.W., Hubbard T., Durbin R.M., Bentley D.R., Beck S., Rogers J.;
RT   "The DNA sequence and comparative analysis of human chromosome 20.";
RL   Nature 414:865-871(2001).
RN   [7]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RX   PubMed=15489334; DOI=10.1101/gr.2596504;
RG   The MGC Project Team;
RT   "The status, quality, and expansion of the NIH full-length cDNA project:
RT   the Mammalian Gene Collection (MGC).";
RL   Genome Res. 14:2121-2127(2004).
RN   [8]
RP   NUCLEOTIDE SEQUENCE [MRNA] OF 26-627 (ISOFORM 1).
RC   TISSUE=Brain;
RA   Mamalaki A., Remoundos M., Tzartos S.;
RT   "Molecular cloning of human neuronal nicotinic acetylcholine receptor 4-
RT   like subunit.";
RL   Submitted (MAY-1995) to the EMBL/GenBank/DDBJ databases.
RN   [9]
RP   INTERACTION WITH RIC3.
RX   PubMed=16120769; DOI=10.1124/mol.105.017459;
RA   Lansdell S.J., Gee V.J., Harkness P.C., Doward A.I., Baker E.R., Gibb A.J.,
RA   Millar N.S.;
RT   "RIC-3 enhances functional expression of multiple nicotinic acetylcholine
RT   receptor subtypes in mammalian cells.";
RL   Mol. Pharmacol. 68:1431-1438(2005).
RN   [10]
RP   INTERACTION WITH LYPD6.
RX   PubMed=27344019; DOI=10.1111/jnc.13718;
RA   Arvaniti M., Jensen M.M., Soni N., Wang H., Klein A.B., Thiriet N.,
RA   Pinborg L.H., Muldoon P.P., Wienecke J., Imad Damaj M., Kohlmeier K.A.,
RA   Gondre-Lewis M.C., Mikkelsen J.D., Thomsen M.S.;
RT   "Functional interaction between Lypd6 and nicotinic acetylcholine
RT   receptors.";
RL   J. Neurochem. 138:806-820(2016).
RN   [11]
RP   STRUCTURE BY NMR OF 242-625, SUBUNIT, AND FUNCTION.
RX   PubMed=22361591; DOI=10.1016/j.bbamem.2012.02.008;
RA   Bondarenko V., Mowrey D., Tillman T., Cui T., Liu L.T., Xu Y., Tang P.;
RT   "NMR structures of the transmembrane domains of the alpha4beta2 nAChR.";
RL   Biochim. Biophys. Acta 1818:1261-1268(2012).
RN   [12]
RP   VARIANT ENFL1 PHE-280.
RX   PubMed=7550350; DOI=10.1038/ng1095-201;
RA   Steinlein O.K., Mulley J.C., Propping P., Wallace R.H., Phillips H.A.,
RA   Sutherland G.R., Scheffer I.E., Berkovic S.F.;
RT   "A missense mutation in the neuronal nicotinic acetylcholine receptor
RT   alpha-4 subunit is associated with autosomal dominant nocturnal frontal
RT   lobe epilepsy.";
RL   Nat. Genet. 11:201-203(1995).
RN   [13]
RP   VARIANT ENFL1 LEU-280.
RX   PubMed=10563623; DOI=10.1212/wnl.53.8.1749;
RA   Hirose S., Iwata H., Akiyoshi H., Kobayashi K., Ito M., Wada K., Kaneko S.,
RA   Mitsudome A.;
RT   "A novel mutation of CHRNA4 responsible for autosomal dominant nocturnal
RT   frontal lobe epilepsy.";
RL   Neurology 53:1749-1753(1999).
RN   [14]
RP   VARIANT ENFL1 LEU-280.
RX   PubMed=14623738; DOI=10.1001/archneur.60.11.1625;
RA   Cho Y.-W., Motamedi G.K., Laufenberg I., Sohn S.-I., Lim J.-G., Lee H.,
RA   Yi S.-D., Lee J.-H., Kim D.-K., Reba R., Gaillard W.D., Theodore W.H.,
RA   Lesser R.P., Steinlein O.K.;
RT   "A Korean kindred with autosomal dominant nocturnal frontal lobe epilepsy
RT   and mental retardation.";
RL   Arch. Neurol. 60:1625-1632(2003).
CC   -!- FUNCTION: After binding acetylcholine, the AChR responds by an
CC       extensive change in conformation that affects all subunits and leads to
CC       opening of an ion-conducting channel across the plasma membrane
CC       permeable to sodium ions. {ECO:0000269|PubMed:22361591}.
CC   -!- SUBUNIT: Neuronal AChR is composed of two different types of subunits:
CC       alpha and beta. Alpha-4 subunit can be combined to beta-2 or beta-4 to
CC       give rise to functional receptors, complexes with beta-2 may be
CC       heteropentamers (PubMed:22361591). Interacts with RIC3; which is
CC       required for proper folding and assembly (PubMed:16120769). Interacts
CC       with LYPD6 (PubMed:27344019). The heteropentamer alpha-4-beta-2
CC       interacts with alpha-conotoxins PnIA, GID and MII (By similarity).
CC       {ECO:0000250|UniProtKB:P09483, ECO:0000269|PubMed:16120769,
CC       ECO:0000269|PubMed:22361591, ECO:0000269|PubMed:27344019}.
CC   -!- INTERACTION:
CC       P43681; Q6UY14-3: ADAMTSL4; NbExp=3; IntAct=EBI-7132379, EBI-10173507;
CC       P43681; P05067: APP; NbExp=3; IntAct=EBI-7132379, EBI-77613;
CC       P43681; P83916: CBX1; NbExp=3; IntAct=EBI-7132379, EBI-78129;
CC       P43681; Q6UXH1-1: CRELD2; NbExp=3; IntAct=EBI-7132379, EBI-21348071;
CC       P43681; Q6UXH1-3: CRELD2; NbExp=3; IntAct=EBI-7132379, EBI-21348090;
CC       P43681; P20042: EIF2S2; NbExp=3; IntAct=EBI-7132379, EBI-711977;
CC       P43681; Q9NZR2: LRP1B; NbExp=3; IntAct=EBI-7132379, EBI-1642131;
CC       P43681; Q92673: SORL1; NbExp=3; IntAct=EBI-7132379, EBI-1171329;
CC       P43681-1; P17787: CHRNB2; NbExp=4; IntAct=EBI-20716158, EBI-9008612;
CC   -!- SUBCELLULAR LOCATION: Postsynaptic cell membrane; Multi-pass membrane
CC       protein. Cell membrane; Multi-pass membrane protein. Cell membrane
CC       {ECO:0000250}; Lipid-anchor {ECO:0000250}.
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Alternative splicing; Named isoforms=2;
CC       Name=1;
CC         IsoId=P43681-1; Sequence=Displayed;
CC       Name=2;
CC         IsoId=P43681-2; Sequence=VSP_054275, VSP_054276;
CC   -!- DISEASE: Epilepsy, nocturnal frontal lobe, 1 (ENFL1) [MIM:600513]: An
CC       autosomal dominant focal epilepsy characterized by nocturnal seizures
CC       with hyperkinetic automatisms and poorly organized stereotyped
CC       movements. {ECO:0000269|PubMed:10563623, ECO:0000269|PubMed:14623738,
CC       ECO:0000269|PubMed:7550350}. Note=The disease is caused by variants
CC       affecting the gene represented in this entry.
CC   -!- SIMILARITY: Belongs to the ligand-gated ion channel (TC 1.A.9) family.
CC       Acetylcholine receptor (TC 1.A.9.1) subfamily. Alpha-4/CHRNA4 sub-
CC       subfamily. {ECO:0000305}.
CC   -!- WEB RESOURCE: Name=NIEHS-SNPs;
CC       URL="http://egp.gs.washington.edu/data/chrna4/";
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DR   EMBL; L35901; AAA64743.1; -; mRNA.
DR   EMBL; X89741; CAA61893.1; -; Genomic_DNA.
DR   EMBL; X89742; CAA61893.1; JOINED; Genomic_DNA.
DR   EMBL; X89743; CAA61893.1; JOINED; Genomic_DNA.
DR   EMBL; X89744; CAA61893.1; JOINED; Genomic_DNA.
DR   EMBL; X89745; CAA61893.1; JOINED; Genomic_DNA.
DR   EMBL; X89746; CAA61893.1; JOINED; Genomic_DNA.
DR   EMBL; U62433; AAB40111.1; -; mRNA.
DR   EMBL; Y08421; CAA69698.1; -; mRNA.
DR   EMBL; DQ093071; AAY88737.1; -; Genomic_DNA.
DR   EMBL; AL121827; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; BC096290; AAH96290.1; -; mRNA.
DR   EMBL; BC096291; AAH96291.1; -; mRNA.
DR   EMBL; X87629; CAA60959.1; -; mRNA.
DR   CCDS; CCDS13517.1; -. [P43681-1]
DR   PIR; JC4021; JC4021.
DR   RefSeq; NP_000735.1; NM_000744.6. [P43681-1]
DR   RefSeq; NP_001243502.1; NM_001256573.1.
DR   RefSeq; XP_011526826.1; XM_011528524.1.
DR   PDB; 2LLY; NMR; -; A=240-339, A=598-626.
DR   PDB; 5KXI; X-ray; 3.94 A; A/D=27-364, A/D=586-627.
DR   PDB; 6CNJ; EM; 3.40 A; A/D=27-364.
DR   PDB; 6CNK; EM; 3.70 A; A/B/D=27-364.
DR   PDB; 6UR8; EM; 3.71 A; A/D=27-364, A/D=589-627.
DR   PDB; 6USF; EM; 3.87 A; A/D=27-358, A/D=589-627.
DR   PDBsum; 2LLY; -.
DR   PDBsum; 5KXI; -.
DR   PDBsum; 6CNJ; -.
DR   PDBsum; 6CNK; -.
DR   PDBsum; 6UR8; -.
DR   PDBsum; 6USF; -.
DR   AlphaFoldDB; P43681; -.
DR   EMDB; EMD-20857; -.
DR   EMDB; EMD-20863; -.
DR   EMDB; EMD-7535; -.
DR   EMDB; EMD-7536; -.
DR   SMR; P43681; -.
DR   BioGRID; 107559; 177.
DR   ComplexPortal; CPX-168; Neuronal nicotinic acetylcholine receptor complex, 3xalpha4-2xbeta2.
DR   ComplexPortal; CPX-218; Neuronal nicotinic acetylcholine receptor complex, alpha4-alpha5-beta2.
DR   ComplexPortal; CPX-2180; Neuronal nicotinic acetylcholine receptor complex, 2xalpha4-3xbeta2.
DR   ComplexPortal; CPX-2203; Neuronal nicotinic acetylcholine receptor complex, alpha4-beta4.
DR   CORUM; P43681; -.
DR   IntAct; P43681; 12.
DR   MINT; P43681; -.
DR   STRING; 9606.ENSP00000359285; -.
DR   BindingDB; P43681; -.
DR   ChEMBL; CHEMBL1882; -.
DR   DrugBank; DB00915; Amantadine.
DR   DrugBank; DB01351; Amobarbital.
DR   DrugBank; DB01352; Aprobarbital.
DR   DrugBank; DB00572; Atropine.
DR   DrugBank; DB01483; Barbital.
DR   DrugBank; DB00237; Butabarbital.
DR   DrugBank; DB00241; Butalbital.
DR   DrugBank; DB01353; Butobarbital.
DR   DrugBank; DB00564; Carbamazepine.
DR   DrugBank; DB00565; Cisatracurium.
DR   DrugBank; DB09028; Cytisine.
DR   DrugBank; DB01245; Decamethonium.
DR   DrugBank; DB00514; Dextromethorphan.
DR   DrugBank; DB01496; Dihydro-2-thioxo-5-((5-(2-(trifluoromethyl)phenyl)-2-furanyl)methyl)-4,6(1H,5H)-pyrimidinedione.
DR   DrugBank; DB07720; Epibatidine.
DR   DrugBank; DB00783; Estradiol.
DR   DrugBank; DB13952; Estradiol acetate.
DR   DrugBank; DB13953; Estradiol benzoate.
DR   DrugBank; DB13954; Estradiol cypionate.
DR   DrugBank; DB13955; Estradiol dienanthate.
DR   DrugBank; DB13956; Estradiol valerate.
DR   DrugBank; DB00898; Ethanol.
DR   DrugBank; DB01354; Heptabarbital.
DR   DrugBank; DB01355; Hexobarbital.
DR   DrugBank; DB00753; Isoflurane.
DR   DrugBank; DB00657; Mecamylamine.
DR   DrugBank; DB00333; Methadone.
DR   DrugBank; DB00463; Metharbital.
DR   DrugBank; DB00849; Methylphenobarbital.
DR   DrugBank; DB00184; Nicotine.
DR   DrugBank; DB00312; Pentobarbital.
DR   DrugBank; DB01174; Phenobarbital.
DR   DrugBank; DB00981; Physostigmine.
DR   DrugBank; DB05458; Pozanicline.
DR   DrugBank; DB00794; Primidone.
DR   DrugBank; DB05740; RPI-78M.
DR   DrugBank; DB00747; Scopolamine.
DR   DrugBank; DB00418; Secobarbital.
DR   DrugBank; DB00202; Succinylcholine.
DR   DrugBank; DB00306; Talbutal.
DR   DrugBank; DB00599; Thiopental.
DR   DrugBank; DB01273; Varenicline.
DR   DrugCentral; P43681; -.
DR   GuidetoPHARMACOLOGY; 465; -.
DR   TCDB; 1.A.9.1.6; the neurotransmitter receptor, cys loop, ligand-gated ion channel (lic) family.
DR   GlyCosmos; P43681; 3 sites, No reported glycans.
DR   GlyGen; P43681; 3 sites.
DR   iPTMnet; P43681; -.
DR   PhosphoSitePlus; P43681; -.
DR   SwissPalm; P43681; -.
DR   BioMuta; CHRNA4; -.
DR   DMDM; 1351848; -.
DR   MassIVE; P43681; -.
DR   PaxDb; 9606-ENSP00000359285; -.
DR   PeptideAtlas; P43681; -.
DR   ProteomicsDB; 55649; -. [P43681-1]
DR   ProteomicsDB; 62290; -.
DR   Antibodypedia; 29717; 322 antibodies from 34 providers.
DR   DNASU; 1137; -.
DR   Ensembl; ENST00000370263.9; ENSP00000359285.4; ENSG00000101204.18. [P43681-1]
DR   GeneID; 1137; -.
DR   KEGG; hsa:1137; -.
DR   MANE-Select; ENST00000370263.9; ENSP00000359285.4; NM_000744.7; NP_000735.1.
DR   UCSC; uc002yes.4; human. [P43681-1]
DR   AGR; HGNC:1958; -.
DR   CTD; 1137; -.
DR   DisGeNET; 1137; -.
DR   GeneCards; CHRNA4; -.
DR   GeneReviews; CHRNA4; -.
DR   HGNC; HGNC:1958; CHRNA4.
DR   HPA; ENSG00000101204; Tissue enhanced (brain, liver, parathyroid gland).
DR   MalaCards; CHRNA4; -.
DR   MIM; 118504; gene.
DR   MIM; 600513; phenotype.
DR   neXtProt; NX_P43681; -.
DR   OpenTargets; ENSG00000101204; -.
DR   Orphanet; 98784; Autosomal dominant nocturnal frontal lobe epilepsy.
DR   PharmGKB; PA26490; -.
DR   VEuPathDB; HostDB:ENSG00000101204; -.
DR   eggNOG; KOG3645; Eukaryota.
DR   GeneTree; ENSGT00940000159329; -.
DR   HOGENOM; CLU_018074_1_1_1; -.
DR   InParanoid; P43681; -.
DR   OMA; CKEPSAV; -.
DR   OrthoDB; 5489962at2759; -.
DR   PhylomeDB; P43681; -.
DR   TreeFam; TF315605; -.
DR   PathwayCommons; P43681; -.
DR   Reactome; R-HSA-629587; Highly sodium permeable postsynaptic acetylcholine nicotinic receptors.
DR   Reactome; R-HSA-629594; Highly calcium permeable postsynaptic nicotinic acetylcholine receptors.
DR   Reactome; R-HSA-629597; Highly calcium permeable nicotinic acetylcholine receptors.
DR   SignaLink; P43681; -.
DR   BioGRID-ORCS; 1137; 13 hits in 1162 CRISPR screens.
DR   GeneWiki; CHRNA4; -.
DR   GenomeRNAi; 1137; -.
DR   Pharos; P43681; Tclin.
DR   PRO; PR:P43681; -.
DR   Proteomes; UP000005640; Chromosome 20.
DR   RNAct; P43681; Protein.
DR   Bgee; ENSG00000101204; Expressed in right lobe of liver and 111 other cell types or tissues.
DR   ExpressionAtlas; P43681; baseline and differential.
DR   GO; GO:0005892; C:acetylcholine-gated channel complex; IDA:UniProtKB.
DR   GO; GO:0030425; C:dendrite; ISS:UniProtKB.
DR   GO; GO:0009897; C:external side of plasma membrane; ISS:UniProtKB.
DR   GO; GO:0016020; C:membrane; ISS:UniProtKB.
DR   GO; GO:0043005; C:neuron projection; IBA:GO_Central.
DR   GO; GO:0043025; C:neuronal cell body; ISS:UniProtKB.
DR   GO; GO:0005886; C:plasma membrane; ISS:UniProtKB.
DR   GO; GO:0045211; C:postsynaptic membrane; IEA:UniProtKB-SubCell.
DR   GO; GO:0045202; C:synapse; IBA:GO_Central.
DR   GO; GO:0042166; F:acetylcholine binding; IC:UniProtKB.
DR   GO; GO:0015464; F:acetylcholine receptor activity; IDA:UniProtKB.
DR   GO; GO:0022848; F:acetylcholine-gated monoatomic cation-selective channel activity; IDA:UniProtKB.
DR   GO; GO:0015276; F:ligand-gated monoatomic ion channel activity; TAS:DFLAT.
DR   GO; GO:0001508; P:action potential; ISS:UniProtKB.
DR   GO; GO:0042113; P:B cell activation; ISS:UniProtKB.
DR   GO; GO:0035095; P:behavioral response to nicotine; IMP:UniProtKB.
DR   GO; GO:0006816; P:calcium ion transport; ISS:UniProtKB.
DR   GO; GO:0007268; P:chemical synaptic transmission; NAS:UniProtKB.
DR   GO; GO:0050890; P:cognition; IMP:UniProtKB.
DR   GO; GO:0006281; P:DNA repair; IMP:UniProtKB.
DR   GO; GO:0060080; P:inhibitory postsynaptic potential; ISS:UniProtKB.
DR   GO; GO:0051899; P:membrane depolarization; ISS:UniProtKB.
DR   GO; GO:0006811; P:monoatomic ion transport; NAS:UniProtKB.
DR   GO; GO:0050877; P:nervous system process; IMP:UniProtKB.
DR   GO; GO:0014059; P:regulation of dopamine secretion; ISS:UniProtKB.
DR   GO; GO:0042391; P:regulation of membrane potential; ISS:UniProtKB.
DR   GO; GO:0001666; P:response to hypoxia; IDA:UniProtKB.
DR   GO; GO:0035094; P:response to nicotine; IDA:UniProtKB.
DR   GO; GO:0006979; P:response to oxidative stress; IMP:UniProtKB.
DR   GO; GO:0019233; P:sensory perception of pain; ISS:UniProtKB.
DR   GO; GO:0007165; P:signal transduction; IDA:UniProtKB.
DR   GO; GO:0007271; P:synaptic transmission, cholinergic; ISS:UniProtKB.
DR   CDD; cd19064; LGIC_TM_nAChR; 1.
DR   Gene3D; 2.70.170.10; Neurotransmitter-gated ion-channel ligand-binding domain; 1.
DR   Gene3D; 1.20.58.390; Neurotransmitter-gated ion-channel transmembrane domain; 2.
DR   InterPro; IPR006202; Neur_chan_lig-bd.
DR   InterPro; IPR036734; Neur_chan_lig-bd_sf.
DR   InterPro; IPR006201; Neur_channel.
DR   InterPro; IPR036719; Neuro-gated_channel_TM_sf.
DR   InterPro; IPR038050; Neuro_actylchol_rec.
DR   InterPro; IPR006029; Neurotrans-gated_channel_TM.
DR   InterPro; IPR018000; Neurotransmitter_ion_chnl_CS.
DR   InterPro; IPR002394; Nicotinic_acetylcholine_rcpt.
DR   NCBIfam; TIGR00860; LIC; 1.
DR   PANTHER; PTHR18945:SF401; NEURONAL ACETYLCHOLINE RECEPTOR SUBUNIT ALPHA-4; 1.
DR   PANTHER; PTHR18945; NEUROTRANSMITTER GATED ION CHANNEL; 1.
DR   Pfam; PF02931; Neur_chan_LBD; 1.
DR   Pfam; PF02932; Neur_chan_memb; 1.
DR   PRINTS; PR00254; NICOTINICR.
DR   PRINTS; PR00252; NRIONCHANNEL.
DR   SUPFAM; SSF90112; Neurotransmitter-gated ion-channel transmembrane pore; 1.
DR   SUPFAM; SSF63712; Nicotinic receptor ligand binding domain-like; 1.
DR   PROSITE; PS00236; NEUROTR_ION_CHANNEL; 1.
DR   Genevisible; P43681; HS.
PE   1: Evidence at protein level;
KW   3D-structure; Alternative splicing; Cell membrane; Disease variant;
KW   Disulfide bond; Epilepsy; Glycoprotein; Ion channel; Ion transport;
KW   Ligand-gated ion channel; Lipoprotein; Membrane; Palmitate; Phosphoprotein;
KW   Postsynaptic cell membrane; Receptor; Reference proteome; Signal; Synapse;
KW   Transmembrane; Transmembrane helix; Transport.
FT   SIGNAL          1..28
FT                   /evidence="ECO:0000255"
FT   CHAIN           29..627
FT                   /note="Neuronal acetylcholine receptor subunit alpha-4"
FT                   /id="PRO_0000000351"
FT   TOPO_DOM        29..242
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        243..267
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        275..293
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        309..330
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        331..600
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        601..619
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   REGION          382..481
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          496..561
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        532..550
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   MOD_RES         424
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:P09483"
FT   MOD_RES         538
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:O70174"
FT   MOD_RES         541
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:O70174"
FT   LIPID           271
FT                   /note="S-palmitoyl cysteine"
FT                   /evidence="ECO:0000250"
FT   CARBOHYD        57
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        107
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        174
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   DISULFID        161..175
FT                   /evidence="ECO:0000250"
FT   DISULFID        225..226
FT                   /note="Associated with receptor activation"
FT                   /evidence="ECO:0000250"
FT   VAR_SEQ         1..57
FT                   /note="MELGGPGAPRLLPPLLLLLGTGLLRASSHVETRAHAEERLLKKLFSGYNKWS
FT                   RPVAN -> MRMSPPSASPPSSSGGRTSSSTTTAGEPFWAGVLFAIRPHPGLSGRIVWT
FT                   AGCPGEG (in isoform 2)"
FT                   /evidence="ECO:0000303|PubMed:15489334"
FT                   /id="VSP_054275"
FT   VAR_SEQ         58..128
FT                   /note="Missing (in isoform 2)"
FT                   /evidence="ECO:0000303|PubMed:15489334"
FT                   /id="VSP_054276"
FT   VARIANT         280
FT                   /note="S -> F (in ENFL1; dbSNP:rs121909580)"
FT                   /evidence="ECO:0000269|PubMed:7550350"
FT                   /id="VAR_000295"
FT   VARIANT         280
FT                   /note="S -> L (in ENFL1)"
FT                   /evidence="ECO:0000269|PubMed:10563623,
FT                   ECO:0000269|PubMed:14623738"
FT                   /id="VAR_017531"
FT   VARIANT         387
FT                   /note="E -> G (in dbSNP:rs45604738)"
FT                   /evidence="ECO:0000269|Ref.5"
FT                   /id="VAR_023402"
FT   VARIANT         517
FT                   /note="S -> L (in dbSNP:rs45622132)"
FT                   /evidence="ECO:0000269|Ref.5"
FT                   /id="VAR_023403"
FT   CONFLICT        4
FT                   /note="G -> E (in Ref. 7; AAH96290)"
FT                   /evidence="ECO:0000305"
FT   HELIX           33..44
FT                   /evidence="ECO:0007829|PDB:6CNJ"
FT   STRAND          50..52
FT                   /evidence="ECO:0007829|PDB:6CNJ"
FT   STRAND          56..59
FT                   /evidence="ECO:0007829|PDB:6CNJ"
FT   STRAND          62..77
FT                   /evidence="ECO:0007829|PDB:6CNJ"
FT   TURN            78..81
FT                   /evidence="ECO:0007829|PDB:6CNJ"
FT   STRAND          82..94
FT                   /evidence="ECO:0007829|PDB:6CNJ"
FT   HELIX           102..104
FT                   /evidence="ECO:0007829|PDB:6CNJ"
FT   STRAND          111..114
FT                   /evidence="ECO:0007829|PDB:6CNJ"
FT   STRAND          123..126
FT                   /evidence="ECO:0007829|PDB:6CNJ"
FT   STRAND          128..131
FT                   /evidence="ECO:0007829|PDB:6CNJ"
FT   STRAND          140..143
FT                   /evidence="ECO:0007829|PDB:6CNJ"
FT   STRAND          145..151
FT                   /evidence="ECO:0007829|PDB:6CNJ"
FT   STRAND          154..159
FT                   /evidence="ECO:0007829|PDB:6CNJ"
FT   STRAND          166..170
FT                   /evidence="ECO:0007829|PDB:6CNJ"
FT   STRAND          172..183
FT                   /evidence="ECO:0007829|PDB:6CNJ"
FT   TURN            186..188
FT                   /evidence="ECO:0007829|PDB:6CNJ"
FT   STRAND          189..194
FT                   /evidence="ECO:0007829|PDB:6CNJ"
FT   STRAND          207..221
FT                   /evidence="ECO:0007829|PDB:6CNJ"
FT   STRAND          230..241
FT                   /evidence="ECO:0007829|PDB:6CNJ"
FT   HELIX           244..247
FT                   /evidence="ECO:0007829|PDB:6CNJ"
FT   TURN            248..250
FT                   /evidence="ECO:0007829|PDB:6CNJ"
FT   HELIX           251..257
FT                   /evidence="ECO:0007829|PDB:6CNJ"
FT   HELIX           258..260
FT                   /evidence="ECO:0007829|PDB:6CNJ"
FT   TURN            261..263
FT                   /evidence="ECO:0007829|PDB:6CNJ"
FT   HELIX           264..266
FT                   /evidence="ECO:0007829|PDB:6CNJ"
FT   STRAND          269..271
FT                   /evidence="ECO:0007829|PDB:6CNJ"
FT   HELIX           274..292
FT                   /evidence="ECO:0007829|PDB:6CNJ"
FT   TURN            293..295
FT                   /evidence="ECO:0007829|PDB:6CNJ"
FT   STRAND          300..302
FT                   /evidence="ECO:0007829|PDB:6CNJ"
FT   HELIX           305..331
FT                   /evidence="ECO:0007829|PDB:6CNJ"
FT   TURN            335..337
FT                   /evidence="ECO:0007829|PDB:6CNJ"
FT   HELIX           342..348
FT                   /evidence="ECO:0007829|PDB:6CNJ"
FT   HELIX           351..355
FT                   /evidence="ECO:0007829|PDB:6CNJ"
SQ   SEQUENCE   627 AA;  69957 MW;  B3A0C0151E5A2AA8 CRC64;
     MELGGPGAPR LLPPLLLLLG TGLLRASSHV ETRAHAEERL LKKLFSGYNK WSRPVANISD
     VVLVRFGLSI AQLIDVDEKN QMMTTNVWVK QEWHDYKLRW DPADYENVTS IRIPSELIWR
     PDIVLYNNAD GDFAVTHLTK AHLFHDGRVQ WTPPAIYKSS CSIDVTFFPF DQQNCTMKFG
     SWTYDKAKID LVNMHSRVDQ LDFWESGEWV IVDAVGTYNT RKYECCAEIY PDITYAFVIR
     RLPLFYTINL IIPCLLISCL TVLVFYLPSE CGEKITLCIS VLLSLTVFLL LITEIIPSTS
     LVIPLIGEYL LFTMIFVTLS IVITVFVLNV HHRSPRTHTM PTWVRRVFLD IVPRLLLMKR
     PSVVKDNCRR LIESMHKMAS APRFWPEPEG EPPATSGTQS LHPPSPSFCV PLDVPAEPGP
     SCKSPSDQLP PQQPLEAEKA SPHPSPGPCR PPHGTQAPGL AKARSLSVQH MSSPGEAVEG
     GVRCRSRSIQ YCVPRDDAAP EADGQAAGAL ASRNTHSAEL PPPDQPSPCK CTCKKEPSSV
     SPSATVKTRS TKAPPPHLPL SPALTRAVEG VQYIADHLKA EDTDFSVKED WKYVAMVIDR
     IFLWMFIIVC LLGTVGLFLP PWLAGMI
//