ACHA9_RAT
ID ACHA9_RAT Reviewed; 479 AA.
AC P43144; Q6PW49;
DT 01-NOV-1995, integrated into UniProtKB/Swiss-Prot.
DT 21-JUN-2005, sequence version 2.
DT 03-AUG-2022, entry version 172.
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=Acra9;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, SUBCELLULAR LOCATION, AND TISSUE
RP SPECIFICITY.
RC TISSUE=Olfactory epithelium;
RX PubMed=7954834; DOI=10.1016/0092-8674(94)90555-x;
RA Elgoyhen A.B., Johnson D.S., Boulter J., Vetter D.E., Heinemann S.F.;
RT "Alpha 9: an acetylcholine receptor with novel pharmacological properties
RT expressed in rat cochlear hair cells.";
RL Cell 79:705-715(1994).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=Sprague-Dawley; TISSUE=Brain;
RA Groot-Kormelink P.J.;
RL Submitted (MAR-2004) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=10713500; DOI=10.1016/s0378-5955(99)00214-2;
RA Katz E., Verbitsky M., Rothlin C.V., Vetter D.E., Heinemann S.F.,
RA Elgoyhen A.B.;
RT "High calcium permeability and calcium block of the alpha9 nicotinic
RT acetylcholine receptor.";
RL Hear. Res. 141:117-128(2000).
RN [4]
RP FUNCTION.
RX PubMed=11044723; DOI=10.1016/s0028-3908(00)00124-6;
RA Verbitsky M., Rothlin C.V., Katz E., Elgoyhen A.B.;
RT "Mixed nicotinic-muscarinic properties of the alpha9 nicotinic cholinergic
RT receptor.";
RL Neuropharmacology 39:2515-2524(2000).
RN [5]
RP INTERACTION WITH CHRNA10, SUBUNIT, TISSUE SPECIFICITY, FUNCTION, AND
RP SUBCELLULAR LOCATION.
RX PubMed=11248107; DOI=10.1073/pnas.051622798;
RA Elgoyhen A.B., Vetter D.E., Katz E., Rothlin C.V., Heinemann S.F.,
RA Boulter J.;
RT "Alpha10: a determinant of nicotinic cholinergic receptor function in
RT mammalian vestibular and cochlear mechanosensory hair cells.";
RL Proc. Natl. Acad. Sci. U.S.A. 98:3501-3506(2001).
RN [6]
RP FUNCTION, SUBCELLULAR LOCATION, AND INTERACTION WITH CHRNA10.
RX PubMed=12117536; DOI=10.1016/s0378-5955(02)00380-5;
RA Weisstaub N., Vetter D.E., Elgoyhen A.B., Katz E.;
RT "The alpha9alpha10 nicotinic acetylcholine receptor is permeable to and is
RT modulated by divalent cations.";
RL Hear. Res. 167:122-135(2002).
RN [7]
RP TISSUE SPECIFICITY.
RX PubMed=12401316; DOI=10.1016/s0306-4522(02)00274-9;
RA Lips K.S., Pfeil U., Kummer W.;
RT "Coexpression of alpha 9 and alpha 10 nicotinic acetylcholine receptors in
RT rat dorsal root ganglion neurons.";
RL Neuroscience 115:1-5(2002).
RN [8]
RP FUNCTION, AND INTERACTION WITH CHRNA10.
RX PubMed=14742688; DOI=10.1124/mol.65.2.453;
RA Baker E.R., Zwart R., Sher E., Millar N.S.;
RT "Pharmacological properties of alpha 9 alpha 10 nicotinic acetylcholine
RT receptors revealed by heterologous expression of subunit chimeras.";
RL Mol. Pharmacol. 65:453-460(2004).
RN [9]
RP SITE THR-86, AND MUTAGENESIS OF SER-36; SER-44; ALA-54; THR-86; ARG-101;
RP SER-147 AND SER-166.
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 [10]
RP MUTAGENESIS OF TRP-176.
RX PubMed=18295795; DOI=10.1016/j.jmb.2008.01.082;
RA Ellison M., Feng Z.P., Park A.J., Zhang X., Olivera B.M., McIntosh J.M.,
RA Norton R.S.;
RT "Alpha-RgIA, a novel conotoxin that blocks the alpha9alpha10 nAChR:
RT structure and identification of key receptor-binding residues.";
RL J. Mol. Biol. 377:1216-1227(2008).
RN [11]
RP SITE ASP-146, MUTAGENESIS OF THR-86 AND ASP-146, AND SUBUNIT.
RX PubMed=25740413; DOI=10.1124/mol.114.096511;
RA Azam L., Papakyriakou A., Zouridakis M., Giastas P., Tzartos S.J.,
RA McIntosh J.M.;
RT "Molecular interaction of alpha-conotoxin RgIA with the rat alpha9alpha10
RT nicotinic acetylcholine receptor.";
RL Mol. Pharmacol. 87:855-864(2015).
RN [12]
RP ERRATUM OF PUBMED:25740413.
RX PubMed=27559150; DOI=10.1124/mol.114.096511err;
RA Azam L., Papakyriakou A., Zouridakis M., Giastas P., Tzartos S.J.,
RA McIntosh J.M.;
RT "Corrections to 'Molecular interaction of alpha-conotoxin RgIA with the rat
RT alpha9alpha10 nicotinic acetylcholine receptor'.";
RL Mol. Pharmacol. 90:415-417(2016).
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. The channel is permeable to a range of divalent cations
CC including calcium, the influx of which may activate a potassium current
CC which hyperpolarizes the cell membrane. In the ear, this leads 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. {ECO:0000269|PubMed:10713500, ECO:0000269|PubMed:11044723,
CC ECO:0000269|PubMed:11248107, ECO:0000269|PubMed:12117536,
CC ECO:0000269|PubMed:14742688, ECO:0000269|PubMed:7954834, ECO:0000305}.
CC -!- SUBUNIT: Can form homo- or heterooligomeric channels in conjunction
CC with CHRNA10. The native outer hair cell receptor may be composed of
CC CHRNA9-CHRNA10 heterooligomers. Interacts with the alpha-conotoxin RgIA
CC (PubMed:25740413). {ECO:0000269|PubMed:11248107,
CC ECO:0000269|PubMed:12117536, ECO:0000269|PubMed:14742688,
CC ECO:0000269|PubMed:25740413, ECO:0000305}.
CC -!- SUBCELLULAR LOCATION: Postsynaptic cell membrane {ECO:0000305}; Multi-
CC pass membrane protein {ECO:0000305}. Cell membrane
CC {ECO:0000269|PubMed:10713500, ECO:0000269|PubMed:11248107,
CC ECO:0000269|PubMed:12117536, ECO:0000269|PubMed:7954834}; Multi-pass
CC membrane protein {ECO:0000305}.
CC -!- TISSUE SPECIFICITY: Detected in the nasal epithelium, in the outer hair
CC cells of the cochlea, in the pars tuberalis of the hypophysis, and in
CC the developing muscle of the tongue. Also expressed in the neurons of
CC dorsal root ganglia. {ECO:0000269|PubMed:11248107,
CC ECO:0000269|PubMed:12401316, ECO:0000269|PubMed:7954834}.
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:0000269|PubMed:7954834}.
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; U12336; AAA56720.1; -; mRNA.
DR EMBL; AY574257; AAS90353.1; -; mRNA.
DR PIR; A55382; A55382.
DR RefSeq; NP_075219.1; NM_022930.1.
DR AlphaFoldDB; P43144; -.
DR SMR; P43144; -.
DR ComplexPortal; CPX-224; Neuronal nicotinic acetylcholine receptor complex, alpha9-alpha10.
DR ComplexPortal; CPX-228; Neuronal nicotinic acetylcholine receptor complex, alpha9.
DR STRING; 10116.ENSRNOP00000003382; -.
DR BindingDB; P43144; -.
DR ChEMBL; CHEMBL2585; -.
DR DrugCentral; P43144; -.
DR GuidetoPHARMACOLOGY; 469; -.
DR GlyGen; P43144; 2 sites.
DR PhosphoSitePlus; P43144; -.
DR PaxDb; P43144; -.
DR DNASU; 65024; -.
DR GeneID; 65024; -.
DR KEGG; rno:65024; -.
DR UCSC; RGD:621534; rat.
DR CTD; 55584; -.
DR RGD; 621534; Chrna9.
DR VEuPathDB; HostDB:ENSRNOG00000002484; -.
DR eggNOG; KOG3645; Eukaryota.
DR HOGENOM; CLU_018074_0_0_1; -.
DR InParanoid; P43144; -.
DR OMA; SPRHDRE; -.
DR OrthoDB; 845098at2759; -.
DR PhylomeDB; P43144; -.
DR TreeFam; TF315605; -.
DR Reactome; R-RNO-629594; Highly calcium permeable postsynaptic nicotinic acetylcholine receptors.
DR PRO; PR:P43144; -.
DR Proteomes; UP000002494; Chromosome 14.
DR Bgee; ENSRNOG00000002484; Expressed in ovary.
DR Genevisible; P43144; RN.
DR GO; GO:0005892; C:acetylcholine-gated channel complex; IDA:RGD.
DR GO; GO:0070161; C:anchoring junction; IEA:UniProtKB-KW.
DR GO; GO:0098981; C:cholinergic synapse; IDA:SynGO.
DR GO; GO:0005887; C:integral component of plasma membrane; ISO:RGD.
DR GO; GO:0099060; C:integral component of postsynaptic specialization membrane; IDA:SynGO.
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:RGD.
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; IDA:SynGO.
DR GO; GO:0006812; P:cation transport; ISO:RGD.
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; ISO:RGD.
DR GO; GO:0042472; P:inner ear morphogenesis; ISO:RGD.
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; IMP:RGD.
DR GO; GO:0050877; P:nervous system process; IBA:GO_Central.
DR GO; GO:0007204; P:positive regulation of cytosolic calcium ion concentration; ISO:RGD.
DR GO; GO:0042391; P:regulation of membrane potential; IBA:GO_Central.
DR GO; GO:0010996; P:response to auditory stimulus; IDA:ComplexPortal.
DR GO; GO:0007605; P:sensory perception of sound; IEP:RGD.
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 Calcium; Calcium channel; Calcium transport; Cell membrane; Disulfide bond;
KW Glycoprotein; Ion channel; Ion transport; Ligand-gated ion channel;
KW Membrane; Postsynaptic cell membrane; Receptor; Reference proteome; Signal;
KW Synapse; Transmembrane; Transmembrane helix; Transport.
FT SIGNAL 1..25
FT /evidence="ECO:0000255"
FT CHAIN 26..479
FT /note="Neuronal acetylcholine receptor subunit alpha-9"
FT /id="PRO_0000000372"
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 86
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:0000269|PubMed:22774872"
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:0000269|PubMed:25740413"
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:0000250|UniProtKB:Q9UGM1"
FT DISULFID 219..220
FT /evidence="ECO:0000250|UniProtKB:Q9UGM1"
FT MUTAGEN 36
FT /note="S->N: No significant change in potency of inhibition
FT of the CHRNA9-CHRNA10 receptor by the alpha-conotoxin
FT RgIA."
FT /evidence="ECO:0000269|PubMed:22774872"
FT MUTAGEN 44
FT /note="S->N: No significant change in potency of inhibition
FT of the CHRNA9-CHRNA10 receptorby the alpha-conotoxin RgIA."
FT /evidence="ECO:0000269|PubMed:22774872"
FT MUTAGEN 54
FT /note="A->K: No significant change in potency of inhibition
FT of the CHRNA9-CHRNA10 receptorby the alpha-conotoxin RgIA."
FT /evidence="ECO:0000269|PubMed:22774872"
FT MUTAGEN 86
FT /note="T->E: The CHRNA9-CHRNA10 receptor is 20-fold less
FT potently inhibited by the alpha-conotoxin RgIA."
FT /evidence="ECO:0000269|PubMed:25740413"
FT MUTAGEN 86
FT /note="T->I: The CHRNA9-CHRNA10 receptor is 1700-fold less
FT potently inhibited by the alpha-conotoxin RgIA."
FT /evidence="ECO:0000269|PubMed:22774872,
FT ECO:0000269|PubMed:25740413"
FT MUTAGEN 101
FT /note="R->G: No significant change in potency of inhibition
FT of the CHRNA9-CHRNA10 receptor by the alpha-conotoxin
FT RgIA."
FT /evidence="ECO:0000269|PubMed:22774872"
FT MUTAGEN 146
FT /note="D->L: Complete loss of inhibition of the CHRNA9-
FT CHRNA10 receptor by the alpha-conotoxin RgIA."
FT /evidence="ECO:0000269|PubMed:25740413"
FT MUTAGEN 147
FT /note="S->A: No significant change in potency of inhibition
FT of the CHRNA9-CHRNA10 receptor by the alpha-conotoxin
FT RgIA."
FT /evidence="ECO:0000269|PubMed:22774872"
FT MUTAGEN 166
FT /note="S->N: No significant change in potency of inhibition
FT of the CHRNA9-CHRNA10 receptor by the alpha-conotoxin
FT RgIA."
FT /evidence="ECO:0000269|PubMed:22774872"
FT MUTAGEN 176
FT /note="W->T: The CHRNA9-CHRNA10 receptor is 8.5-fold less
FT potently inhibited by the alpha-conotoxin RgIA."
FT /evidence="ECO:0000269|PubMed:18295795"
FT CONFLICT 425
FT /note="T -> A (in Ref. 1; AAA56720)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 479 AA; 54526 MW; CBB3E15E9DF68837 CRC64;
MNRPHSCLSF CWMYFAASGI RAVETANGKY AQKLFSDLFE DYSSALRPVE DTDAVLNVTL
QVTLSQIKDM DERNQILTAY LWIRQTWHDA YLTWDRDQYD RLDSIRIPSD LVWRPDIVLY
NKADDESSEP VNTNVVLRYD GLITWDSPAI TKSSCVVDVT YFPFDSQQCN LTFGSWTYNG
NQVDIFNALD SGDLSDFIED VEWEVHGMPA VKNVISYGCC SEPYPDVTFT LLLKRRSSFY
IVNLLIPCVL ISFLAPLSFY LPAASGEKVS LGVTILLAMT VFQLMVAEIM PASENVPLIG
KYYIATMALI TASTALTIMV MNIHFCGAEA RPVPHWAKVV ILKYMSRILF VYDVGESCLS
PRHSQEPEQV TKVYSKLPES NLKTSRNKDL SRKKEVRKLL KNDLGYQGGI PQNTDSYCAR
YEALTKNIEY IAKCLKDHKA TNSKGSEWKK VAKVIDRFFM WIFFAMVFVM TVLIIARAD
