ACHA6_HUMAN
ID ACHA6_HUMAN Reviewed; 494 AA.
AC Q15825; B2R8V4; B4DQH1;
DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1997, sequence version 1.
DT 03-AUG-2022, entry version 194.
DE RecName: Full=Neuronal acetylcholine receptor subunit alpha-6;
DE Flags: Precursor;
GN Name=CHRNA6;
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=Substantia nigra;
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 [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RA Groot Kormelink P.J.;
RL Submitted (JAN-1998) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RA Ebihara M., Ohba H., Yoshikawa T.;
RT "Alu and other elements in the promoter of human nAChR A6 gene (CHNRA6)
RT direct transcriptional repression.";
RL Submitted (FEB-2002) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16421571; DOI=10.1038/nature04406;
RA Nusbaum C., Mikkelsen T.S., Zody M.C., Asakawa S., Taudien S., Garber M.,
RA Kodira C.D., Schueler M.G., Shimizu A., Whittaker C.A., Chang J.L.,
RA Cuomo C.A., Dewar K., FitzGerald M.G., Yang X., Allen N.R., Anderson S.,
RA Asakawa T., Blechschmidt K., Bloom T., Borowsky M.L., Butler J., Cook A.,
RA Corum B., DeArellano K., DeCaprio D., Dooley K.T., Dorris L. III,
RA Engels R., Gloeckner G., Hafez N., Hagopian D.S., Hall J.L., Ishikawa S.K.,
RA Jaffe D.B., Kamat A., Kudoh J., Lehmann R., Lokitsang T., Macdonald P.,
RA Major J.E., Matthews C.D., Mauceli E., Menzel U., Mihalev A.H.,
RA Minoshima S., Murayama Y., Naylor J.W., Nicol R., Nguyen C., O'Leary S.B.,
RA O'Neill K., Parker S.C.J., Polley A., Raymond C.K., Reichwald K.,
RA Rodriguez J., Sasaki T., Schilhabel M., Siddiqui R., Smith C.L.,
RA Sneddon T.P., Talamas J.A., Tenzin P., Topham K., Venkataraman V., Wen G.,
RA Yamazaki S., Young S.K., Zeng Q., Zimmer A.R., Rosenthal A., Birren B.W.,
RA Platzer M., Shimizu N., Lander E.S.;
RT "DNA sequence and analysis of human chromosome 8.";
RL Nature 439:331-335(2006).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Skin;
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 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 types of
CC subunits: alpha and non-alpha (beta). Interacts with LYPD6
CC (PubMed:27344019). {ECO:0000269|PubMed:27344019}.
CC -!- SUBCELLULAR LOCATION: Postsynaptic cell membrane; Multi-pass membrane
CC protein. Cell membrane; Multi-pass membrane protein.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q15825-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q15825-2; Sequence=VSP_042713;
CC -!- SIMILARITY: Belongs to the ligand-gated ion channel (TC 1.A.9) family.
CC Acetylcholine receptor (TC 1.A.9.1) subfamily. Alpha-6/CHRNA6 sub-
CC subfamily. {ECO:0000305}.
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DR EMBL; U62435; AAB40113.1; -; mRNA.
DR EMBL; Y16282; CAA76155.1; -; mRNA.
DR EMBL; AB079251; BAC06855.1; -; Genomic_DNA.
DR EMBL; AK298798; BAG60933.1; -; mRNA.
DR EMBL; AK313521; BAG36301.1; -; mRNA.
DR EMBL; AC087533; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471080; EAW63207.1; -; Genomic_DNA.
DR EMBL; BC014456; AAH14456.1; -; mRNA.
DR CCDS; CCDS56536.1; -. [Q15825-2]
DR CCDS; CCDS6135.1; -. [Q15825-1]
DR RefSeq; NP_001186208.1; NM_001199279.1. [Q15825-2]
DR RefSeq; NP_004189.1; NM_004198.3. [Q15825-1]
DR AlphaFoldDB; Q15825; -.
DR SMR; Q15825; -.
DR BioGRID; 114463; 1.
DR ComplexPortal; CPX-213; Neuronal nicotinic acetylcholine receptor complex, alpha3-alpha6-beta4.
DR ComplexPortal; CPX-2192; Neuronal nicotinic acetylcholine receptor complex, alpha3-alpha6-beta2-beta3.
DR IntAct; Q15825; 3.
DR STRING; 9606.ENSP00000276410; -.
DR BindingDB; Q15825; -.
DR ChEMBL; CHEMBL2109233; -.
DR ChEMBL; CHEMBL2109237; -.
DR ChEMBL; CHEMBL3137285; -.
DR DrugBank; DB00237; Butabarbital.
DR DrugBank; DB09028; Cytisine.
DR DrugBank; DB00898; Ethanol.
DR DrugBank; DB00184; Nicotine.
DR DrugBank; DB00202; Succinylcholine.
DR DrugBank; DB01273; Varenicline.
DR DrugCentral; Q15825; -.
DR GuidetoPHARMACOLOGY; 467; -.
DR GlyGen; Q15825; 2 sites.
DR iPTMnet; Q15825; -.
DR PhosphoSitePlus; Q15825; -.
DR BioMuta; CHRNA6; -.
DR DMDM; 2492620; -.
DR MassIVE; Q15825; -.
DR PaxDb; Q15825; -.
DR PRIDE; Q15825; -.
DR ProteomicsDB; 60777; -. [Q15825-1]
DR ProteomicsDB; 60778; -. [Q15825-2]
DR Antibodypedia; 24152; 154 antibodies from 25 providers.
DR DNASU; 8973; -.
DR Ensembl; ENST00000276410.7; ENSP00000276410.3; ENSG00000147434.9. [Q15825-1]
DR Ensembl; ENST00000534622.5; ENSP00000433871.1; ENSG00000147434.9. [Q15825-2]
DR GeneID; 8973; -.
DR KEGG; hsa:8973; -.
DR MANE-Select; ENST00000276410.7; ENSP00000276410.3; NM_004198.3; NP_004189.1.
DR UCSC; uc003xpj.5; human. [Q15825-1]
DR CTD; 8973; -.
DR DisGeNET; 8973; -.
DR GeneCards; CHRNA6; -.
DR HGNC; HGNC:15963; CHRNA6.
DR HPA; ENSG00000147434; Group enriched (brain, retina).
DR MIM; 606888; gene.
DR neXtProt; NX_Q15825; -.
DR OpenTargets; ENSG00000147434; -.
DR PharmGKB; PA26492; -.
DR VEuPathDB; HostDB:ENSG00000147434; -.
DR eggNOG; KOG3645; Eukaryota.
DR GeneTree; ENSGT00940000158062; -.
DR HOGENOM; CLU_018074_1_0_1; -.
DR InParanoid; Q15825; -.
DR OMA; PKVLLMQ; -.
DR OrthoDB; 381858at2759; -.
DR PhylomeDB; Q15825; -.
DR TreeFam; TF315605; -.
DR PathwayCommons; Q15825; -.
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; Q15825; -.
DR BioGRID-ORCS; 8973; 8 hits in 1065 CRISPR screens.
DR ChiTaRS; CHRNA6; human.
DR GeneWiki; CHRNA6; -.
DR GenomeRNAi; 8973; -.
DR Pharos; Q15825; Tchem.
DR PRO; PR:Q15825; -.
DR Proteomes; UP000005640; Chromosome 8.
DR RNAct; Q15825; protein.
DR Bgee; ENSG00000147434; Expressed in tibialis anterior and 70 other tissues.
DR ExpressionAtlas; Q15825; baseline and differential.
DR Genevisible; Q15825; HS.
DR GO; GO:0005892; C:acetylcholine-gated channel complex; TAS:ProtInc.
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:0099055; C:integral component of postsynaptic membrane; IEA:Ensembl.
DR GO; GO:0099056; C:integral component of presynaptic membrane; IEA:Ensembl.
DR GO; GO:0043005; C:neuron projection; IBA:GO_Central.
DR GO; GO:0005886; C:plasma membrane; TAS:Reactome.
DR GO; GO:0045202; C:synapse; IBA:GO_Central.
DR GO; GO:0015464; F:acetylcholine receptor activity; TAS:ProtInc.
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: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: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; IEA:Ensembl.
DR GO; GO:0050877; P:nervous system process; IBA:GO_Central.
DR GO; GO:0014059; P:regulation of dopamine secretion; IEA:Ensembl.
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:0007165; P:signal transduction; 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; 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 Alternative splicing; Cell membrane; Disulfide bond; Glycoprotein;
KW Ion channel; Ion transport; Ligand-gated ion channel; Membrane;
KW Phosphoprotein; Postsynaptic cell membrane; Receptor; Reference proteome;
KW Signal; Synapse; Transmembrane; Transmembrane helix; Transport.
FT SIGNAL 1..25
FT /evidence="ECO:0000255"
FT CHAIN 26..494
FT /note="Neuronal acetylcholine receptor subunit alpha-6"
FT /id="PRO_0000000360"
FT TOPO_DOM 26..239
FT /note="Extracellular"
FT TRANSMEM 240..264
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 272..290
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 306..327
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 328..465
FT /note="Cytoplasmic"
FT TRANSMEM 466..484
FT /note="Helical"
FT /evidence="ECO:0000255"
FT MOD_RES 401
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P04757"
FT CARBOHYD 54
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 171
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 158..172
FT /evidence="ECO:0000250"
FT DISULFID 222..223
FT /note="Associated with receptor activation"
FT /evidence="ECO:0000250"
FT VAR_SEQ 74..88
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_042713"
FT VARIANT 447
FT /note="N -> S (in dbSNP:rs16891583)"
FT /id="VAR_048171"
SQ SEQUENCE 494 AA; 56898 MW; 1A437E6DEE02ABFE CRC64;
MLTSKGQGFL HGGLCLWLCV FTPFFKGCVG CATEERLFHK LFSHYNQFIR PVENVSDPVT
VHFEVAITQL ANVDEVNQIM ETNLWLRHIW NDYKLRWDPM EYDGIETLRV PADKIWKPDI
VLYNNAVGDF QVEGKTKALL KYNGMITWTP PAIFKSSCPM DITFFPFDHQ NCSLKFGSWT
YDKAEIDLLI IGSKVDMNDF WENSEWEIID ASGYKHDIKY NCCEEIYTDI TYSFYIRRLP
MFYTINLIIP CLFISFLTVL VFYLPSDCGE KVTLCISVLL SLTVFLLVIT ETIPSTSLVV
PLVGEYLLFT MIFVTLSIVV TVFVLNIHYR TPTTHTMPRW VKTVFLKLLP QVLLMRWPLD
KTRGTGSDAV PRGLARRPAK GKLASHGEPR HLKECFHCHK SNELATSKRR LSHQPLQWVV
ENSEHSPEVE DVINSVQFIA ENMKSHNETK EVEDDWKYVA MVVDRVFLWV FIIVCVFGTA
GLFLQPLLGN TGKS
