ACHA4_HUMAN
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 03-AUG-2022, entry version 216.
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/";
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
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. [P43681-2]
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 SMR; P43681; -.
DR BioGRID; 107559; 176.
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; 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 GlyGen; P43681; 3 sites.
DR iPTMnet; P43681; -.
DR PhosphoSitePlus; P43681; -.
DR SwissPalm; P43681; -.
DR BioMuta; CHRNA4; -.
DR DMDM; 1351848; -.
DR MassIVE; P43681; -.
DR PaxDb; P43681; -.
DR PeptideAtlas; P43681; -.
DR PRIDE; P43681; -.
DR ProteomicsDB; 55649; -. [P43681-1]
DR ProteomicsDB; 62290; -.
DR Antibodypedia; 29717; 287 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 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; IFPAFGH; -.
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; 12 hits in 1078 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 109 other tissues.
DR ExpressionAtlas; P43681; baseline and differential.
DR Genevisible; P43681; HS.
DR GO; GO:0005892; C:acetylcholine-gated channel complex; IDA:UniProtKB.
DR GO; GO:0070161; C:anchoring junction; IEA:UniProtKB-KW.
DR GO; GO:0030425; C:dendrite; ISS:UniProtKB.
DR GO; GO:0009897; C:external side of plasma membrane; ISS:UniProtKB.
DR GO; GO:0016021; C:integral component of membrane; NAS:UniProtKB.
DR GO; GO:0005887; C:integral component of plasma membrane; IBA:GO_Central.
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 cation-selective channel activity; IDA:UniProtKB.
DR GO; GO:0005231; F:excitatory extracellular ligand-gated ion channel activity; IBA:GO_Central.
DR GO; GO:0015276; F:ligand-gated ion channel activity; TAS:DFLAT.
DR GO; GO:0030594; F:neurotransmitter receptor activity; IBA:GO_Central.
DR GO; GO:1904315; F:transmitter-gated ion channel activity involved in regulation of postsynaptic membrane potential; IBA:GO_Central.
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; IBA:GO_Central.
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:0034220; P:ion transmembrane transport; IBA:GO_Central.
DR GO; GO:0006811; P:ion transport; NAS:UniProtKB.
DR GO; GO:0051899; P:membrane depolarization; IDA:ComplexPortal.
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 Gene3D; 1.20.58.390; -; 2.
DR Gene3D; 2.70.170.10; -; 1.
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 PANTHER; PTHR18945; PTHR18945; 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; SSF63712; SSF63712; 1.
DR SUPFAM; SSF90112; SSF90112; 1.
DR TIGRFAMs; TIGR00860; LIC; 1.
DR PROSITE; PS00236; NEUROTR_ION_CHANNEL; 1.
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
