ACHA9_HUMAN
ID ACHA9_HUMAN Reviewed; 479 AA.
AC Q9UGM1; Q14CY7; Q4W5A2; Q9NYV2;
DT 27-APR-2001, integrated into UniProtKB/Swiss-Prot.
DT 05-OCT-2010, sequence version 2.
DT 03-AUG-2022, entry version 182.
DE RecName: Full=Neuronal acetylcholine receptor subunit alpha-9;
DE AltName: Full=Nicotinic acetylcholine receptor subunit alpha-9;
DE Short=NACHR alpha-9;
DE Flags: Precursor;
GN Name=CHRNA9; Synonyms=NACHRA9;
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], FUNCTION, INTERACTION WITH CHRNA10, SUBUNIT,
RP SUBCELLULAR LOCATION, TISSUE SPECIFICITY, AND VARIANT SER-442.
RC TISSUE=Embryo;
RX PubMed=11752216; DOI=10.1124/mol.61.1.150;
RA Sgard F., Charpantier E., Bertrand S., Walker N., Caput D., Graham D.,
RA Bertrand D., Besnard F.;
RT "A novel human nicotinic receptor subunit, alpha10, that confers
RT functionality to the alpha9-subunit.";
RL Mol. Pharmacol. 61:150-159(2002).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANT SER-442.
RX PubMed=12697997; DOI=10.1159/000069804;
RA Lustig L.R., Peng H.;
RT "Chromosome location and characterization of the human nicotinic
RT acetylcholine receptor subunit alpha (alpha) 9 (CHRNA9) gene.";
RL Cytogenet. Genome Res. 98:154-159(2002).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15815621; DOI=10.1038/nature03466;
RA Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P.,
RA Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C.,
RA Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L.,
RA Du H., Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A.,
RA Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J.,
RA Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M.,
RA Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T.,
RA Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S.,
RA Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K.,
RA McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C.,
RA Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S.,
RA Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C.,
RA Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M.,
RA Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C.,
RA Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J.,
RA Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E.,
RA Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X.,
RA Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M.,
RA Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C.,
RA Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S.,
RA Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H.,
RA Wilson R.K.;
RT "Generation and annotation of the DNA sequences of human chromosomes 2 and
RT 4.";
RL Nature 434:724-731(2005).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT SER-442.
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 [5]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 7-476, FUNCTION, AND TISSUE SPECIFICITY.
RX PubMed=11021840; DOI=10.1016/s0002-9440(10)64651-2;
RA Nguyen V.T., Ndoye A., Grando S.A.;
RT "Novel human alpha9 acetylcholine receptor regulating keratinocyte adhesion
RT is targeted by Pemphigus vulgaris autoimmunity.";
RL Am. J. Pathol. 157:1377-1391(2000).
RN [6]
RP TISSUE SPECIFICITY.
RX PubMed=15531379; DOI=10.1016/j.lfs.2004.05.031;
RA Peng H., Ferris R.L., Matthews T., Hiel H., Lopez-Albaitero A.,
RA Lustig L.R.;
RT "Characterization of the human nicotinic acetylcholine receptor subunit
RT alpha (alpha) 9 (CHRNA9) and alpha (alpha) 10 (CHRNA10) in lymphocytes.";
RL Life Sci. 76:263-280(2004).
RN [7]
RP MUTAGENESIS OF ILE-86, AND SUBUNIT.
RX PubMed=22774872; DOI=10.1111/j.1471-4159.2012.07867.x;
RA Azam L., McIntosh J.M.;
RT "Molecular basis for the differential sensitivity of rat and human
RT alpha9alpha10 nAChRs to alpha-conotoxin RgIA.";
RL J. Neurochem. 122:1137-1144(2012).
RN [8]
RP X-RAY CRYSTALLOGRAPHY (1.71 ANGSTROMS) OF 26-237, FUNCTION, SUBCELLULAR
RP LOCATION, DISULFIDE BOND, AND GLYCOSYLATION.
RX PubMed=25282151; DOI=10.1038/nsmb.2900;
RA Zouridakis M., Giastas P., Zarkadas E., Chroni-Tzartou D., Bregestovski P.,
RA Tzartos S.J.;
RT "Crystal structures of free and antagonist-bound states of human alpha9
RT nicotinic receptor extracellular domain.";
RL Nat. Struct. Mol. Biol. 21:976-980(2014).
CC -!- FUNCTION: Ionotropic receptor with a probable role in the modulation of
CC auditory stimuli. Agonist binding induces a conformation change that
CC leads to the opening of an ion-conducting channel across the plasma
CC membrane (PubMed:11752216, PubMed:25282151). The channel is permeable
CC to a range of divalent cations including calcium, the influx of which
CC may activate a potassium current which hyperpolarizes the cell membrane
CC (PubMed:11752216, PubMed:25282151). In the ear, this may lead to a
CC reduction in basilar membrane motion, altering the activity of auditory
CC nerve fibers and reducing the range of dynamic hearing. This may
CC protect against acoustic trauma. May also regulate keratinocyte
CC adhesion (PubMed:11021840). {ECO:0000269|PubMed:11021840,
CC ECO:0000269|PubMed:11752216, ECO:0000269|PubMed:25282151, ECO:0000305}.
CC -!- SUBUNIT: Can form homo- or heterooligomeric channels in conjunction
CC with CHRNA10 (PubMed:11752216). The native outer hair cell receptor may
CC be composed of CHRNA9-CHRNA10 heterooligomers. Interacts with the
CC alpha-conotoxon RgIA (PubMed:22774872). {ECO:0000269|PubMed:11752216,
CC ECO:0000269|PubMed:22774872}.
CC -!- INTERACTION:
CC Q9UGM1; P60616; Xeno; NbExp=2; IntAct=EBI-9008641, EBI-16123259;
CC -!- SUBCELLULAR LOCATION: Postsynaptic cell membrane {ECO:0000305}; Multi-
CC pass membrane protein {ECO:0000305}. Cell membrane
CC {ECO:0000269|PubMed:25282151}; Multi-pass membrane protein
CC {ECO:0000305|PubMed:25282151}.
CC -!- TISSUE SPECIFICITY: Expressed in cochlea, keratinocytes, pituitary
CC gland, B-cells and T-cells. {ECO:0000269|PubMed:11021840,
CC ECO:0000269|PubMed:11752216, ECO:0000269|PubMed:15531379}.
CC -!- PTM: N-glycosylated. {ECO:0000269|PubMed:25282151}.
CC -!- MISCELLANEOUS: The heterooligomeric receptor composed of CHRNA9 and
CC CHRNA10 has an atypical pharmacological profile, binding several non-
CC nicotinic ligands including strychnine (a glycine receptor antagonist)
CC and atropine (a muscarinic acetylcholine receptor antagonist).
CC {ECO:0000305|PubMed:11752216}.
CC -!- SIMILARITY: Belongs to the ligand-gated ion channel (TC 1.A.9) family.
CC Acetylcholine receptor (TC 1.A.9.1) subfamily. Alpha-9/CHRNA9 sub-
CC subfamily. {ECO:0000305}.
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DR EMBL; AJ243342; CAB65091.1; -; mRNA.
DR EMBL; AY123244; AAM74523.1; -; Genomic_DNA.
DR EMBL; AC118275; AAY40986.1; -; Genomic_DNA.
DR EMBL; BC113549; AAI13550.1; -; mRNA.
DR EMBL; BC113575; AAI13576.1; -; mRNA.
DR EMBL; AF227732; AAF61920.1; -; mRNA.
DR CCDS; CCDS3459.1; -.
DR RefSeq; NP_060051.2; NM_017581.3.
DR PDB; 4D01; X-ray; 1.80 A; A=26-237.
DR PDB; 4UXU; X-ray; 1.71 A; A/B=26-237.
DR PDB; 4UY2; X-ray; 2.70 A; A/B=26-237.
DR PDB; 6HY7; X-ray; 2.26 A; A=26-237.
DR PDBsum; 4D01; -.
DR PDBsum; 4UXU; -.
DR PDBsum; 4UY2; -.
DR PDBsum; 6HY7; -.
DR AlphaFoldDB; Q9UGM1; -.
DR SMR; Q9UGM1; -.
DR BioGRID; 120731; 80.
DR ComplexPortal; CPX-2171; Neuronal nicotinic acetylcholine receptor complex, alpha9-alpha10.
DR ComplexPortal; CPX-226; Neuronal nicotinic acetylcholine receptor complex, alpha9.
DR CORUM; Q9UGM1; -.
DR DIP; DIP-61053N; -.
DR IntAct; Q9UGM1; 48.
DR STRING; 9606.ENSP00000312663; -.
DR BindingDB; Q9UGM1; -.
DR ChEMBL; CHEMBL2184; -.
DR DrugBank; DB05069; ATG003.
DR DrugBank; DB00237; Butabarbital.
DR DrugBank; DB00898; Ethanol.
DR DrugBank; DB05137; Lobeline.
DR DrugBank; DB00184; Nicotine.
DR DrugBank; DB05740; RPI-78M.
DR DrugBank; DB00202; Succinylcholine.
DR DrugBank; DB08837; Tetraethylammonium.
DR GuidetoPHARMACOLOGY; 469; -.
DR TCDB; 1.A.9.1.22; the neurotransmitter receptor, cys loop, ligand-gated ion channel (lic) family.
DR GlyGen; Q9UGM1; 2 sites.
DR iPTMnet; Q9UGM1; -.
DR PhosphoSitePlus; Q9UGM1; -.
DR BioMuta; CHRNA9; -.
DR DMDM; 308153406; -.
DR jPOST; Q9UGM1; -.
DR MassIVE; Q9UGM1; -.
DR MaxQB; Q9UGM1; -.
DR PaxDb; Q9UGM1; -.
DR PeptideAtlas; Q9UGM1; -.
DR PRIDE; Q9UGM1; -.
DR ProteomicsDB; 84234; -.
DR Antibodypedia; 11757; 114 antibodies from 25 providers.
DR DNASU; 55584; -.
DR Ensembl; ENST00000310169.3; ENSP00000312663.2; ENSG00000174343.6.
DR GeneID; 55584; -.
DR KEGG; hsa:55584; -.
DR MANE-Select; ENST00000310169.3; ENSP00000312663.2; NM_017581.4; NP_060051.2.
DR UCSC; uc003gva.2; human.
DR CTD; 55584; -.
DR DisGeNET; 55584; -.
DR GeneCards; CHRNA9; -.
DR HGNC; HGNC:14079; CHRNA9.
DR HPA; ENSG00000174343; Not detected.
DR MIM; 605116; gene.
DR neXtProt; NX_Q9UGM1; -.
DR OpenTargets; ENSG00000174343; -.
DR PharmGKB; PA26493; -.
DR VEuPathDB; HostDB:ENSG00000174343; -.
DR eggNOG; KOG3645; Eukaryota.
DR GeneTree; ENSGT00940000156077; -.
DR HOGENOM; CLU_018074_0_0_1; -.
DR InParanoid; Q9UGM1; -.
DR OMA; SPRHDRE; -.
DR OrthoDB; 845098at2759; -.
DR PhylomeDB; Q9UGM1; -.
DR TreeFam; TF315605; -.
DR PathwayCommons; Q9UGM1; -.
DR Reactome; R-HSA-629594; Highly calcium permeable postsynaptic nicotinic acetylcholine receptors.
DR Reactome; R-HSA-9667769; Acetylcholine inhibits contraction of outer hair cells.
DR SignaLink; Q9UGM1; -.
DR BioGRID-ORCS; 55584; 7 hits in 1067 CRISPR screens.
DR ChiTaRS; CHRNA9; human.
DR GeneWiki; CHRNA9; -.
DR GenomeRNAi; 55584; -.
DR Pharos; Q9UGM1; Tchem.
DR PRO; PR:Q9UGM1; -.
DR Proteomes; UP000005640; Chromosome 4.
DR RNAct; Q9UGM1; protein.
DR Bgee; ENSG00000174343; Expressed in penis and 62 other tissues.
DR Genevisible; Q9UGM1; 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:0098981; C:cholinergic synapse; IEA:Ensembl.
DR GO; GO:0005887; C:integral component of plasma membrane; IDA:UniProtKB.
DR GO; GO:0099060; C:integral component of postsynaptic specialization 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:0022848; F:acetylcholine-gated cation-selective channel activity; IDA:UniProtKB.
DR GO; GO:0005262; F:calcium channel activity; IEA:UniProtKB-KW.
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:0004888; F:transmembrane signaling receptor activity; IEA:InterPro.
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:0050910; P:detection of mechanical stimulus involved in sensory perception of sound; IEA:Ensembl.
DR GO; GO:0042472; P:inner ear morphogenesis; IEA:Ensembl.
DR GO; GO:0034220; P:ion transmembrane transport; IBA:GO_Central.
DR GO; GO:0051899; P:membrane depolarization; IDA:ComplexPortal.
DR GO; GO:0070373; P:negative regulation of ERK1 and ERK2 cascade; IEA:Ensembl.
DR GO; GO:0050877; P:nervous system process; IBA:GO_Central.
DR GO; GO:0007204; P:positive regulation of cytosolic calcium ion concentration; IGI:MGI.
DR GO; GO:0042391; P:regulation of membrane potential; IBA:GO_Central.
DR GO; GO:0080164; P:regulation of nitric oxide metabolic process; IDA:ComplexPortal.
DR GO; GO:0010996; P:response to auditory stimulus; 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; 2.
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; Calcium; Calcium channel; Calcium transport; Cell membrane;
KW 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..25
FT /evidence="ECO:0000255"
FT CHAIN 26..479
FT /note="Neuronal acetylcholine receptor subunit alpha-9"
FT /id="PRO_0000000371"
FT TOPO_DOM 26..237
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 238..262
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 269..287
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 302..323
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 324..457
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 458..476
FT /note="Helical"
FT /evidence="ECO:0000255"
FT SITE 146
FT /note="Key residue important for potent inhibition of the
FT CHRNA9-CHRNA10 receptor by the alpha-conotoxin RgIA (AC
FT P0C1D0)"
FT /evidence="ECO:0000250|UniProtKB:P43144"
FT CARBOHYD 57
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 170
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 155..169
FT /evidence="ECO:0000269|PubMed:25282151"
FT DISULFID 219..220
FT /evidence="ECO:0000269|PubMed:25282151"
FT VARIANT 96
FT /note="R -> Q (in dbSNP:rs10024518)"
FT /id="VAR_031151"
FT VARIANT 315
FT /note="A -> V (in dbSNP:rs55633891)"
FT /id="VAR_060996"
FT VARIANT 442
FT /note="N -> S (in dbSNP:rs10009228)"
FT /evidence="ECO:0000269|PubMed:11752216,
FT ECO:0000269|PubMed:12697997, ECO:0000269|PubMed:15489334"
FT /id="VAR_025425"
FT MUTAGEN 86
FT /note="I->T: The CHRNA9-CHRNA10 receptor is 250-fold more
FT potently inhibited by the alpha-conotoxin RgIA."
FT /evidence="ECO:0000269|PubMed:22774872"
FT HELIX 30..39
FT /evidence="ECO:0007829|PDB:4UXU"
FT STRAND 49..51
FT /evidence="ECO:0007829|PDB:4UY2"
FT STRAND 56..71
FT /evidence="ECO:0007829|PDB:4UXU"
FT TURN 72..75
FT /evidence="ECO:0007829|PDB:4UXU"
FT STRAND 76..93
FT /evidence="ECO:0007829|PDB:4UXU"
FT HELIX 96..98
FT /evidence="ECO:0007829|PDB:4UXU"
FT TURN 99..101
FT /evidence="ECO:0007829|PDB:4UXU"
FT STRAND 104..108
FT /evidence="ECO:0007829|PDB:4UXU"
FT HELIX 109..111
FT /evidence="ECO:0007829|PDB:4UXU"
FT STRAND 117..119
FT /evidence="ECO:0007829|PDB:4UXU"
FT STRAND 134..138
FT /evidence="ECO:0007829|PDB:4UXU"
FT STRAND 140..154
FT /evidence="ECO:0007829|PDB:4UXU"
FT STRAND 156..158
FT /evidence="ECO:0007829|PDB:4UXU"
FT STRAND 164..177
FT /evidence="ECO:0007829|PDB:4UXU"
FT TURN 180..182
FT /evidence="ECO:0007829|PDB:4UXU"
FT STRAND 183..191
FT /evidence="ECO:0007829|PDB:4UXU"
FT STRAND 201..207
FT /evidence="ECO:0007829|PDB:4UXU"
FT STRAND 209..217
FT /evidence="ECO:0007829|PDB:4UXU"
FT TURN 218..220
FT /evidence="ECO:0007829|PDB:4UXU"
FT STRAND 224..235
FT /evidence="ECO:0007829|PDB:4UXU"
SQ SEQUENCE 479 AA; 54807 MW; AA6B46B559D6111D CRC64;
MNWSHSCISF CWIYFAASRL RAAETADGKY AQKLFNDLFE DYSNALRPVE DTDKVLNVTL
QITLSQIKDM DERNQILTAY LWIRQIWHDA YLTWDRDQYD GLDSIRIPSD LVWRPDIVLY
NKADDESSEP VNTNVVLRYD GLITWDAPAI TKSSCVVDVT YFPFDNQQCN LTFGSWTYNG
NQVDIFNALD SGDLSDFIED VEWEVHGMPA VKNVISYGCC SEPYPDVTFT LLLKRRSSFY
IVNLLIPCVL ISFLAPLSFY LPAASGEKVS LGVTILLAMT VFQLMVAEIM PASENVPLIG
KYYIATMALI TASTALTIMV MNIHFCGAEA RPVPHWARVV ILKYMSRVLF VYDVGESCLS
PHHSRERDHL TKVYSKLPES NLKAARNKDL SRKKDMNKRL KNDLGCQGKN PQEAESYCAQ
YKVLTRNIEY IAKCLKDHKA TNSKGSEWKK VAKVIDRFFM WIFFIMVFVM TILIIARAD
