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ACH10_HUMAN
ID   ACH10_HUMAN             Reviewed;         450 AA.
AC   Q9GZZ6;
DT   11-JUL-2001, integrated into UniProtKB/Swiss-Prot.
DT   01-MAR-2001, sequence version 1.
DT   03-AUG-2022, entry version 182.
DE   RecName: Full=Neuronal acetylcholine receptor subunit alpha-10;
DE   AltName: Full=Nicotinic acetylcholine receptor subunit alpha-10;
DE            Short=NACHR alpha-10;
DE   Flags: Precursor;
GN   Name=CHRNA10; Synonyms=NACHRA10;
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 CHRNA9, AND TISSUE
RP   SPECIFICITY.
RC   TISSUE=Skeletal muscle;
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].
RC   TISSUE=Inner ear, and Tonsil;
RX   PubMed=11350119; DOI=10.1006/geno.2000.6503;
RA   Lustig L.R., Peng H., Hiel H., Yamamoto T., Fuchs P.A.;
RT   "Molecular cloning and mapping of the human nicotinic acetylcholine
RT   receptor alpha10 (CHRNA10).";
RL   Genomics 73:272-283(2001).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RA   Vandenberk I., van der Helm L., Nieuwstraten D.M., Verfaille C., Kremer A.,
RA   van der Spek P., Masure S., Hoefnagel E., Yon J., Groot Kormelink P.J.,
RA   Luyten W.H., Grantham C.J.;
RT   "Identification and functional characterisation of a novel human neuronal
RT   nicotinic acetylcholine receptor subunit alpha 10.";
RL   Submitted (NOV-2000) to the EMBL/GenBank/DDBJ databases.
RN   [4]
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   [5]
RP   MUTAGENESIS OF LEU-31, AND INTERACTION WITH THE CONOTOXIN GEXXA.
RX   PubMed=26395518; DOI=10.1038/srep14261;
RA   Xu S., Zhang T., Kompella S.N., Yan M., Lu A., Wang Y., Shao X., Chi C.,
RA   Adams D.J., Ding J., Wang C.;
RT   "Conotoxin alphaD-GeXXA utilizes a novel strategy to antagonize nicotinic
RT   acetylcholine receptors.";
RL   Sci. Rep. 5:14261-14268(2015).
CC   -!- FUNCTION: Ionotropic receptor with a probable role in the modulation of
CC       auditory stimuli. Agonist binding may induce an extensive change in
CC       conformation that affects all subunits and leads to opening of an ion-
CC       conducting channel across the plasma membrane. 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
CC       membrane. In the ear, this may lead to a reduction in basilar membrane
CC       motion, altering the activity of auditory nerve fibers and reducing the
CC       range of dynamic hearing. This may protect against acoustic trauma.
CC       {ECO:0000269|PubMed:11752216}.
CC   -!- SUBUNIT: Forms heterooligomeric channels in conjunction with CHRNA9.
CC       The native outer hair cell receptor may be composed of CHRNA9-CHRNA10
CC       heterooligomers. Interacts with the conotoxin GeXXA (PubMed:26395518).
CC       Interacts with the alpha-conotoxin RgIA (By similarity).
CC       {ECO:0000250|UniProtKB:Q9JLB5, ECO:0000269|PubMed:26395518}.
CC   -!- SUBCELLULAR LOCATION: Postsynaptic cell membrane {ECO:0000305}; Multi-
CC       pass membrane protein {ECO:0000305}. Cell membrane {ECO:0000305};
CC       Multi-pass membrane protein {ECO:0000305}.
CC   -!- TISSUE SPECIFICITY: Expressed in inner-ear tissue, tonsil, immortalized
CC       B-cells, cultured T-cells and peripheral blood lymphocytes.
CC       {ECO:0000269|PubMed:11752216, ECO:0000269|PubMed:15531379}.
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   -!- SIMILARITY: Belongs to the ligand-gated ion channel (TC 1.A.9) family.
CC       Acetylcholine receptor (TC 1.A.9.1) subfamily. Alpha-10/CHRNA10 sub-
CC       subfamily. {ECO:0000305}.
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DR   EMBL; AJ278118; CAC20435.1; -; mRNA.
DR   EMBL; AF199235; AAG00795.2; -; mRNA.
DR   EMBL; AF327367; AAK14333.1; -; Genomic_DNA.
DR   EMBL; AJ295237; CAC16144.1; -; mRNA.
DR   CCDS; CCDS7745.1; -.
DR   RefSeq; NP_001289963.1; NM_001303034.1.
DR   RefSeq; NP_001289964.1; NM_001303035.1.
DR   RefSeq; NP_065135.2; NM_020402.3.
DR   AlphaFoldDB; Q9GZZ6; -.
DR   SMR; Q9GZZ6; -.
DR   BioGRID; 121345; 18.
DR   ComplexPortal; CPX-2171; Neuronal nicotinic acetylcholine receptor complex, alpha9-alpha10.
DR   CORUM; Q9GZZ6; -.
DR   STRING; 9606.ENSP00000250699; -.
DR   BindingDB; Q9GZZ6; -.
DR   ChEMBL; CHEMBL2109238; -.
DR   DrugBank; DB05069; ATG003.
DR   DrugBank; DB00237; Butabarbital.
DR   DrugBank; DB14783; Diroximel fumarate.
DR   DrugBank; DB00898; Ethanol.
DR   DrugBank; DB05137; Lobeline.
DR   DrugBank; DB00184; Nicotine.
DR   DrugBank; DB01090; Pentolinium.
DR   DrugBank; DB05740; RPI-78M.
DR   DrugBank; DB00202; Succinylcholine.
DR   DrugBank; DB01116; Trimethaphan.
DR   DrugCentral; Q9GZZ6; -.
DR   GuidetoPHARMACOLOGY; 470; -.
DR   TCDB; 1.A.9.1.22; the neurotransmitter receptor, cys loop, ligand-gated ion channel (lic) family.
DR   GlyGen; Q9GZZ6; 2 sites.
DR   iPTMnet; Q9GZZ6; -.
DR   PhosphoSitePlus; Q9GZZ6; -.
DR   BioMuta; CHRNA10; -.
DR   DMDM; 14916526; -.
DR   MassIVE; Q9GZZ6; -.
DR   PaxDb; Q9GZZ6; -.
DR   PeptideAtlas; Q9GZZ6; -.
DR   PRIDE; Q9GZZ6; -.
DR   Antibodypedia; 57559; 212 antibodies from 24 providers.
DR   DNASU; 57053; -.
DR   Ensembl; ENST00000250699.2; ENSP00000250699.2; ENSG00000129749.3.
DR   GeneID; 57053; -.
DR   KEGG; hsa:57053; -.
DR   MANE-Select; ENST00000250699.2; ENSP00000250699.2; NM_020402.4; NP_065135.2.
DR   UCSC; uc001lyf.3; human.
DR   CTD; 57053; -.
DR   DisGeNET; 57053; -.
DR   GeneCards; CHRNA10; -.
DR   HGNC; HGNC:13800; CHRNA10.
DR   HPA; ENSG00000129749; Tissue enriched (skeletal).
DR   MIM; 606372; gene.
DR   neXtProt; NX_Q9GZZ6; -.
DR   OpenTargets; ENSG00000129749; -.
DR   PharmGKB; PA26488; -.
DR   VEuPathDB; HostDB:ENSG00000129749; -.
DR   eggNOG; KOG3645; Eukaryota.
DR   GeneTree; ENSGT00940000160721; -.
DR   HOGENOM; CLU_018074_0_0_1; -.
DR   InParanoid; Q9GZZ6; -.
DR   OMA; QSNYMMS; -.
DR   OrthoDB; 845098at2759; -.
DR   PhylomeDB; Q9GZZ6; -.
DR   TreeFam; TF315605; -.
DR   PathwayCommons; Q9GZZ6; -.
DR   Reactome; R-HSA-9667769; Acetylcholine inhibits contraction of outer hair cells.
DR   SignaLink; Q9GZZ6; -.
DR   BioGRID-ORCS; 57053; 13 hits in 1068 CRISPR screens.
DR   GeneWiki; CHRNA10; -.
DR   GenomeRNAi; 57053; -.
DR   Pharos; Q9GZZ6; Tchem.
DR   PRO; PR:Q9GZZ6; -.
DR   Proteomes; UP000005640; Chromosome 11.
DR   RNAct; Q9GZZ6; protein.
DR   Bgee; ENSG00000129749; Expressed in gastrocnemius and 96 other tissues.
DR   ExpressionAtlas; Q9GZZ6; baseline and differential.
DR   Genevisible; Q9GZZ6; HS.
DR   GO; GO:0005892; C:acetylcholine-gated channel complex; IC:ComplexPortal.
DR   GO; GO:0070161; C:anchoring junction; IEA:UniProtKB-KW.
DR   GO; GO:0030424; C:axon; IEA:Ensembl.
DR   GO; GO:0098981; C:cholinergic synapse; IEA:Ensembl.
DR   GO; GO:0005887; C:integral component of plasma membrane; IBA:GO_Central.
DR   GO; GO:0099060; C:integral component of postsynaptic specialization membrane; IEA:Ensembl.
DR   GO; GO:0016020; C:membrane; TAS:UniProtKB.
DR   GO; GO:0043005; C:neuron projection; IBA:GO_Central.
DR   GO; GO:0043204; C:perikaryon; IEA:Ensembl.
DR   GO; GO:0045202; C:synapse; IBA:GO_Central.
DR   GO; GO:0022848; F:acetylcholine-gated cation-selective channel activity; IBA:GO_Central.
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:0005102; F:signaling receptor binding; TAS:UniProtKB.
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:0042127; P:regulation of cell population proliferation; TAS:UniProtKB.
DR   GO; GO:0042391; P:regulation of membrane potential; IBA:GO_Central.
DR   GO; GO:0010996; P:response to auditory stimulus; IEA:Ensembl.
DR   GO; GO:0007165; P:signal transduction; IBA:GO_Central.
DR   GO; GO:0007271; P:synaptic transmission, cholinergic; TAS: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; 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..24
FT                   /evidence="ECO:0000255"
FT   CHAIN           25..450
FT                   /note="Neuronal acetylcholine receptor subunit alpha-10"
FT                   /id="PRO_0000000376"
FT   TOPO_DOM        25..237
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        238..258
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        268..288
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        302..322
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        323..428
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        429..449
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   REGION          355..380
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        362..376
FT                   /note="Pro residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   CARBOHYD        40
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        56
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   DISULFID        154..168
FT                   /evidence="ECO:0000250"
FT   DISULFID        218..219
FT                   /note="Associated with receptor activation"
FT                   /evidence="ECO:0000250"
FT   VARIANT         355
FT                   /note="E -> A (in dbSNP:rs2231547)"
FT                   /id="VAR_048172"
FT   MUTAGEN         31
FT                   /note="L->H: 11-fold increase in inhibition of the AChR
FT                   composed of subunits CHRNA9 and CHRNA10 by the conotoxin
FT                   GEXXA, and no change in activity on mAChR composed of
FT                   subunits CHRNA9 and CHRNA10 by the competitive conotoxin
FT                   Vc1A."
FT                   /evidence="ECO:0000269|PubMed:26395518"
SQ   SEQUENCE   450 AA;  49705 MW;  0A1DAD32D9069870 CRC64;
     MGLRSHHLSL GLLLLFLLPA ECLGAEGRLA LKLFRDLFAN YTSALRPVAD TDQTLNVTLE
     VTLSQIIDMD ERNQVLTLYL WIRQEWTDAY LRWDPNAYGG LDAIRIPSSL VWRPDIVLYN
     KADAQPPGSA STNVVLRHDG AVRWDAPAIT RSSCRVDVAA FPFDAQHCGL TFGSWTHGGH
     QLDVRPRGAA ASLADFVENV EWRVLGMPAR RRVLTYGCCS EPYPDVTFTL LLRRRAAAYV
     CNLLLPCVLI SLLAPLAFHL PADSGEKVSL GVTVLLALTV FQLLLAESMP PAESVPLIGK
     YYMATMTMVT FSTALTILIM NLHYCGPSVR PVPAWARALL LGHLARGLCV RERGEPCGQS
     RPPELSPSPQ SPEGGAGPPA GPCHEPRCLC RQEALLHHVA TIANTFRSHR AAQRCHEDWK
     RLARVMDRFF LAIFFSMALV MSLLVLVQAL
 
 
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