ACHA5_HUMAN
ID ACHA5_HUMAN Reviewed; 468 AA.
AC P30532; Q15824; Q99554;
DT 01-APR-1993, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1997, sequence version 2.
DT 03-AUG-2022, entry version 200.
DE RecName: Full=Neuronal acetylcholine receptor subunit alpha-5;
DE Flags: Precursor;
GN Name=CHRNA5; Synonyms=NACHRA5;
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].
RX PubMed=1542648; DOI=10.1073/pnas.89.5.1572;
RA Chini B., Clementi F., Hukovic N., Sher E.;
RT "Neuronal-type alpha-bungarotoxin receptors and the alpha 5-nicotinic
RT receptor subunit gene are expressed in neuronal and nonneuronal human cell
RT lines.";
RL Proc. Natl. Acad. Sci. U.S.A. 89:1572-1576(1992).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA], AND VARIANT ASN-398.
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 [3]
RP NUCLEOTIDE SEQUENCE [MRNA].
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 [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANT ASN-398.
RA Duga S., Solda G., Asselta R., Bonati M.T., Dalpra L., Malcovati M.,
RA Tenchini M.L.;
RT "Characterization of the genomic structure of human nicotinic acetylcholine
RT receptor CHRNA5/A3/B4 gene cluster: identification of two novel introns in
RT the 3' untranslated region of CHRNA3 and of a tail-to-tail overlap between
RT CHRNA3 and CHRNA5.";
RL Submitted (MAR-2001) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Eye;
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 [6]
RP INVOLVEMENT IN SQTL3 AND LUNG CANCER.
RX PubMed=18385720; DOI=10.1038/452537a;
RA Chanock S.J., Hunter D.J.;
RT "Genomics: when the smoke clears.";
RL Nature 452:537-538(2008).
RN [7]
RP INVOLVEMENT IN SQTL3 AND LUNG CANCER.
RX PubMed=18385738; DOI=10.1038/nature06885;
RA Hung R.J., McKay J.D., Gaborieau V., Boffetta P., Hashibe M., Zaridze D.,
RA Mukeria A., Szeszenia-Dabrowska N., Lissowska J., Rudnai P., Fabianova E.,
RA Mates D., Bencko V., Foretova L., Janout V., Chen C., Goodman G.,
RA Field J.K., Liloglou T., Xinarianos G., Cassidy A., McLaughlin J., Liu G.,
RA Narod S., Krokan H.E., Skorpen F., Elvestad M.B., Hveem K., Vatten L.,
RA Linseisen J., Clavel-Chapelon F., Vineis P., Bueno-de-Mesquita H.B.,
RA Lund E., Martinez C., Bingham S., Rasmuson T., Hainaut P., Riboli E.,
RA Ahrens W., Benhamou S., Lagiou P., Trichopoulos D., Holcatova I.,
RA Merletti F., Kjaerheim K., Agudo A., Macfarlane G., Talamini R.,
RA Simonato L., Lowry R., Conway D.I., Znaor A., Healy C., Zelenika D.,
RA Boland A., Delepine M., Foglio M., Lechner D., Matsuda F., Blanche H.,
RA Gut I., Heath S., Lathrop M., Brennan P.;
RT "A susceptibility locus for lung cancer maps to nicotinic acetylcholine
RT receptor subunit genes on 15q25.";
RL Nature 452:633-637(2008).
RN [8]
RP INVOLVEMENT IN SQTL3 AND LUNG CANCER.
RX PubMed=18385676; DOI=10.1038/ng.109;
RA Amos C.I., Wu X., Broderick P., Gorlov I.P., Gu J., Eisen T., Dong Q.,
RA Zhang Q., Gu X., Vijayakrishnan J., Sullivan K., Matakidou A., Wang Y.,
RA Mills G., Doheny K., Tsai Y.-Y., Chen W.V., Shete S., Spitz M.R.,
RA Houlston R.S.;
RT "Genome-wide association scan of tag SNPs identifies a susceptibility locus
RT for lung cancer at 15q25.1.";
RL Nat. Genet. 40:616-622(2008).
RN [9]
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).
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 -!- SUBUNIT: Neuronal AChR seems to be composed of two different type of
CC subunits: alpha and non-alpha (beta). Interacts with LYPD6
CC (PubMed:27344019). {ECO:0000269|PubMed:27344019}.
CC -!- INTERACTION:
CC P30532; P17787: CHRNB2; NbExp=3; IntAct=EBI-6657490, EBI-9008612;
CC -!- SUBCELLULAR LOCATION: Postsynaptic cell membrane; Multi-pass membrane
CC protein. Cell membrane; Multi-pass membrane protein.
CC -!- POLYMORPHISM: Genetic variations in CHRNA5 have been associated with
CC susceptibility to smoking-related behavioral traits and lung cancer,
CC contributing to the smoking quantitative trait locus 3 (SQTL3)
CC [MIM:612052].
CC -!- SIMILARITY: Belongs to the ligand-gated ion channel (TC 1.A.9) family.
CC Acetylcholine receptor (TC 1.A.9.1) subfamily. Alpha-5/CHRNA5 sub-
CC subfamily. {ECO:0000305}.
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DR EMBL; M83712; AAA58357.1; -; mRNA.
DR EMBL; U62434; AAB40112.1; -; mRNA.
DR EMBL; Y08419; CAA69696.1; -; mRNA.
DR EMBL; AJ306481; CAC34820.1; -; Genomic_DNA.
DR EMBL; AJ306482; CAC34820.1; JOINED; Genomic_DNA.
DR EMBL; AJ306483; CAC34820.1; JOINED; Genomic_DNA.
DR EMBL; AJ306484; CAC34820.1; JOINED; Genomic_DNA.
DR EMBL; AJ306485; CAC34820.1; JOINED; Genomic_DNA.
DR EMBL; AJ306486; CAC34820.1; JOINED; Genomic_DNA.
DR EMBL; BC033639; AAH33639.1; -; mRNA.
DR CCDS; CCDS10304.1; -.
DR PIR; A38223; A38223.
DR RefSeq; NP_000736.2; NM_000745.3.
DR AlphaFoldDB; P30532; -.
DR SMR; P30532; -.
DR BioGRID; 107560; 117.
DR ComplexPortal; CPX-187; Neuronal nicotinic acetylcholine receptor complex, alpha3-alpha5-beta2.
DR ComplexPortal; CPX-210; Neuronal nicotinic acetylcholine receptor complex, alpha3-alpha5-beta4.
DR ComplexPortal; CPX-218; Neuronal nicotinic acetylcholine receptor complex, alpha4-alpha5-beta2.
DR IntAct; P30532; 9.
DR STRING; 9606.ENSP00000299565; -.
DR BindingDB; P30532; -.
DR ChEMBL; CHEMBL3038461; -.
DR ChEMBL; CHEMBL3137272; -.
DR ChEMBL; CHEMBL3137273; -.
DR DrugBank; DB00237; Butabarbital.
DR DrugBank; DB00898; Ethanol.
DR DrugBank; DB00184; Nicotine.
DR DrugBank; DB00202; Succinylcholine.
DR GlyGen; P30532; 3 sites.
DR iPTMnet; P30532; -.
DR PhosphoSitePlus; P30532; -.
DR BioMuta; CHRNA5; -.
DR DMDM; 2506126; -.
DR MassIVE; P30532; -.
DR MaxQB; P30532; -.
DR PaxDb; P30532; -.
DR PeptideAtlas; P30532; -.
DR PRIDE; P30532; -.
DR ProteomicsDB; 54715; -.
DR Antibodypedia; 15098; 336 antibodies from 36 providers.
DR DNASU; 1138; -.
DR Ensembl; ENST00000299565.9; ENSP00000299565.5; ENSG00000169684.13.
DR GeneID; 1138; -.
DR KEGG; hsa:1138; -.
DR MANE-Select; ENST00000299565.9; ENSP00000299565.5; NM_000745.4; NP_000736.2.
DR UCSC; uc002bdy.3; human.
DR CTD; 1138; -.
DR DisGeNET; 1138; -.
DR GeneCards; CHRNA5; -.
DR HGNC; HGNC:1959; CHRNA5.
DR HPA; ENSG00000169684; Low tissue specificity.
DR MalaCards; CHRNA5; -.
DR MIM; 118505; gene.
DR MIM; 612052; phenotype.
DR neXtProt; NX_P30532; -.
DR OpenTargets; ENSG00000169684; -.
DR PharmGKB; PA26491; -.
DR VEuPathDB; HostDB:ENSG00000169684; -.
DR eggNOG; KOG3645; Eukaryota.
DR GeneTree; ENSGT00940000159270; -.
DR HOGENOM; CLU_018074_1_2_1; -.
DR InParanoid; P30532; -.
DR OMA; KWANIII; -.
DR OrthoDB; 381858at2759; -.
DR PhylomeDB; P30532; -.
DR TreeFam; TF315605; -.
DR PathwayCommons; P30532; -.
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; P30532; -.
DR BioGRID-ORCS; 1138; 8 hits in 1075 CRISPR screens.
DR GeneWiki; CHRNA5; -.
DR GenomeRNAi; 1138; -.
DR Pharos; P30532; Tbio.
DR PRO; PR:P30532; -.
DR Proteomes; UP000005640; Chromosome 15.
DR RNAct; P30532; protein.
DR Bgee; ENSG00000169684; Expressed in ventricular zone and 106 other tissues.
DR ExpressionAtlas; P30532; baseline and differential.
DR Genevisible; P30532; HS.
DR GO; GO:0005892; C:acetylcholine-gated channel complex; IPI:ComplexPortal.
DR GO; GO:0070161; C:anchoring junction; IEA:UniProtKB-KW.
DR GO; GO:0098691; C:dopaminergic synapse; IEA:Ensembl.
DR GO; GO:0005887; C:integral component of plasma membrane; IBA:GO_Central.
DR GO; GO:0043005; C:neuron projection; IBA:GO_Central.
DR GO; GO:0005886; C:plasma membrane; TAS:Reactome.
DR GO; GO:0045211; C:postsynaptic membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0045202; C:synapse; IBA:GO_Central.
DR GO; GO:0015464; F:acetylcholine receptor activity; IDA:UniProtKB.
DR GO; GO:0022848; F:acetylcholine-gated cation-selective channel activity; IBA:GO_Central.
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:0035095; P:behavioral response to nicotine; IMP:UniProtKB.
DR GO; GO:0007268; P:chemical synaptic transmission; IBA:GO_Central.
DR GO; GO:0034220; P:ion transmembrane transport; IBA:GO_Central.
DR GO; GO:0051899; P:membrane depolarization; IDA:ComplexPortal.
DR GO; GO:0050877; P:nervous system process; IBA:GO_Central.
DR GO; GO:0042391; P:regulation of membrane potential; IBA:GO_Central.
DR GO; GO:2000300; P:regulation of synaptic vesicle exocytosis; IEA:Ensembl.
DR GO; GO:0035094; P:response to nicotine; IBA:GO_Central.
DR GO; GO:0007165; P:signal transduction; IBA:GO_Central.
DR GO; GO:0007271; P:synaptic transmission, cholinergic; IBA:GO_Central.
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; 2.
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 Cell membrane; Disulfide bond; Glycoprotein; Ion channel; Ion transport;
KW Ligand-gated ion channel; Membrane; Postsynaptic cell membrane; Receptor;
KW Reference proteome; Signal; Synapse; Transmembrane; Transmembrane helix;
KW Transport.
FT SIGNAL 1..22
FT /evidence="ECO:0000255"
FT CHAIN 23..468
FT /note="Neuronal acetylcholine receptor subunit alpha-5"
FT /id="PRO_0000000356"
FT TOPO_DOM 23..254
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 255..275
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 282..302
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 317..337
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 338..429
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 430..451
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 452..468
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT CARBOHYD 155
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 183
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 229
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 170..184
FT /evidence="ECO:0000250"
FT DISULFID 234..235
FT /note="Associated with receptor activation"
FT /evidence="ECO:0000250"
FT VARIANT 134
FT /note="V -> I (in dbSNP:rs2229961)"
FT /id="VAR_046211"
FT VARIANT 398
FT /note="D -> N (associated with susceptibility to lung
FT cancer; dbSNP:rs16969968)"
FT /evidence="ECO:0000269|PubMed:8906617, ECO:0000269|Ref.4"
FT /id="VAR_046212"
FT CONFLICT 23..34
FT /note="RCGLAGAAGGAQ -> ALRSSRARRAAR (in Ref. 1; AAA58357)"
FT /evidence="ECO:0000305"
FT CONFLICT 128
FT /note="V -> S (in Ref. 1; AAA58357)"
FT /evidence="ECO:0000305"
FT CONFLICT 365
FT /note="C -> S (in Ref. 1; AAA58357)"
FT /evidence="ECO:0000305"
FT CONFLICT 405
FT /note="R -> T (in Ref. 1; AAA58357)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 468 AA; 53054 MW; 7FE91A2E362289C0 CRC64;
MAARGSGPRA LRLLLLVQLV AGRCGLAGAA GGAQRGLSEP SSIAKHEDSL LKDLFQDYER
WVRPVEHLND KIKIKFGLAI SQLVDVDEKN QLMTTNVWLK QEWIDVKLRW NPDDYGGIKV
IRVPSDSVWT PDIVLFDNAD GRFEGTSTKT VIRYNGTVTW TPPANYKSSC TIDVTFFPFD
LQNCSMKFGS WTYDGSQVDI ILEDQDVDKR DFFDNGEWEI VSATGSKGNR TDSCCWYPYV
TYSFVIKRLP LFYTLFLIIP CIGLSFLTVL VFYLPSNEGE KICLCTSVLV SLTVFLLVIE
EIIPSSSKVI PLIGEYLVFT MIFVTLSIMV TVFAINIHHR SSSTHNAMAP LVRKIFLHTL
PKLLCMRSHV DRYFTQKEET ESGSGPKSSR NTLEAALDSI RYITRHIMKE NDVREVVEDW
KFIAQVLDRM FLWTFLFVSI VGSLGLFVPV IYKWANILIP VHIGNANK
