ID   ACHA6_RAT               Reviewed;         493 AA.
AC   P43143;
DT   01-NOV-1995, integrated into UniProtKB/Swiss-Prot.
DT   01-NOV-1995, sequence version 1.
DT   02-SEP-2026, entry version 166.
DE   RecName: Full=Neuronal acetylcholine receptor subunit alpha-6;
DE   Flags: Precursor;
GN   Name=Chrna6; Synonyms=Acra6;
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].
RA   Boulter J.;
RT   "Nucleotide sequence of a cDNA clone encoding the rat neuronal nicotinic
RT   acetylcholine receptor subunit gene alpha6.";
RL   Submitted (DEC-1992) to the EMBL/GenBank/DDBJ databases.
RN   [2]
RP   FUNCTION, ACTIVITY REGULATION, SUBCELLULAR LOCATION, AND CATALYTIC
RP   ACTIVITY.
RX   PubMed=21325521; DOI=10.1523/jneurosci.3003-10.2011;
RA   Yang K., Buhlman L., Khan G.M., Nichols R.A., Jin G., McIntosh J.M.,
RA   Whiteaker P., Lukas R.J., Wu J.;
RT   "Functional nicotinic acetylcholine receptors containing alpha6 subunits
RT   are on GABAergic neuronal boutons adherent to ventral tegmental area
RT   dopamine neurons.";
RL   J. Neurosci. 31:2537-2548(2011).
CC   -!- FUNCTION: Component of neuronal acetylcholine receptors (nAChRs) that
CC       function as pentameric, ligand-gated cation channels with high calcium
CC       permeability among other activities. nAChRs are excitatory
CC       neurotrasnmitter receptors formed by a collection of nAChR subunits
CC       known to mediate synaptic transmission in the nervous system and the
CC       neuromuscular junction. Each nAchR subunit confers differential
CC       attributes to channel properties, including activation, deactivation
CC       and desensitization kinetics, pH sensitivity, cation permeability, and
CC       binding to allosteric modulators. CHRNA6 forms pentameric channels with
CC       CHRNB2 and CHRNA4 that exhibit high sensitivity to ACh and nicotine and
CC       are predominantly expressed in only a few brain areas, including
CC       dopaminergic neurons, norepirephrine neurons and cells of the visual
CC       system (By similarity). nAChrs containing CHRNA6 subunits mediate
CC       endogenous cholinergic modulation of dopamine and gamma-aminobutyric
CC       acid (GABA) release in response to nicotine at nerve terminals
CC       (PubMed:21325521). {ECO:0000250|UniProtKB:Q9R0W9,
CC       ECO:0000269|PubMed:21325521}.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=Ca(2+)(in) = Ca(2+)(out); Xref=Rhea:RHEA:29671,
CC         ChEBI:CHEBI:29108; Evidence={ECO:0000269|PubMed:21325521};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=K(+)(in) = K(+)(out); Xref=Rhea:RHEA:29463, ChEBI:CHEBI:29103;
CC         Evidence={ECO:0000250|UniProtKB:P02709};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=Na(+)(in) = Na(+)(out); Xref=Rhea:RHEA:34963,
CC         ChEBI:CHEBI:29101; Evidence={ECO:0000250|UniProtKB:P02709};
CC   -!- ACTIVITY REGULATION: Activated by a myriad of ligands such as
CC       acetylcholine, cytisine and nicotine. CHRNA6 nAChR activity is
CC       inhibited by the antagonists alpha-conotoxin MII and PIA, a small
CC       disulfide-constrained peptides from cone snails.
CC       {ECO:0000269|PubMed:21325521}.
CC   -!- SUBUNIT: Neuronal AChR is composed of two different types of subunits:
CC       alpha and non-alpha (beta). CHRNA6/alpha-6 subunit can be combined to
CC       CHRNB2/beta-2 and CHRNA4/alpha-4 to give rise to functional receptors
CC       (PubMed:21325521). Interacts with LYPD6 (By similarity).
CC       {ECO:0000250|UniProtKB:Q15825, ECO:0000250|UniProtKB:Q9R0W9,
CC       ECO:0000269|PubMed:21325521}.
CC   -!- SUBCELLULAR LOCATION: Synaptic cell membrane
CC       {ECO:0000269|PubMed:21325521}; Multi-pass membrane protein
CC       {ECO:0000255}.
CC   -!- TISSUE SPECIFICITY: Predominantly expressed in only a few brain areas,
CC       including dopaminergic neurons, norepirephrine neurons and cells of the
CC       visual system. {ECO:0000269|PubMed:21325521}.
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; L08227; AAA41674.1; -; mRNA.
DR   RefSeq; NP_476532.2; NM_057184.2.
DR   AlphaFoldDB; P43143; -.
DR   SMR; P43143; -.
DR   ComplexPortal; CPX-203; Neuronal nicotinic acetylcholine receptor complex, alpha3-alpha6-beta2-beta3.
DR   ComplexPortal; CPX-211; Neuronal nicotinic acetylcholine receptor complex, alpha3-alpha6-beta4.
DR   FunCoup; P43143; 39.
DR   IntAct; P43143; 2.
DR   STRING; 10116.ENSRNOP00000016452; -.
DR   BindingDB; P43143; -.
DR   ChEMBL; CHEMBL4747; -.
DR   DrugCentral; P43143; -.
DR   GlyCosmos; P43143; 2 sites, No reported glycans.
DR   GlyGen; P43143; 2 sites.
DR   PhosphoSitePlus; P43143; -.
DR   PaxDb; 10116-ENSRNOP00000016452; -.
DR   GeneID; 81721; -.
DR   KEGG; rno:81721; -.
DR   UCSC; RGD:69281; rat.
DR   AGR; RGD:69281; -.
DR   CTD; 8973; -.
DR   RGD; 69281; Chrna6.
DR   eggNOG; KOG3645; Eukaryota.
DR   InParanoid; P43143; -.
DR   PhylomeDB; P43143; -.
DR   Reactome; R-RNO-629594; Highly calcium permeable postsynaptic nicotinic acetylcholine receptors.
DR   Reactome; R-RNO-629597; Highly calcium permeable nicotinic acetylcholine receptors.
DR   PRO; PR:P43143; -.
DR   Proteomes; UP000002494; Unplaced.
DR   GO; GO:0005892; C:acetylcholine-gated channel complex; ISO:RGD.
DR   GO; GO:0098691; C:dopaminergic synapse; ISS:UniProtKB.
DR   GO; GO:0043005; C:neuron projection; IBA:GO_Central.
DR   GO; GO:0005886; C:plasma membrane; IBA:GO_Central.
DR   GO; GO:0045211; C:postsynaptic membrane; IDA:SynGO.
DR   GO; GO:0042734; C:presynaptic membrane; IDA:SynGO.
DR   GO; GO:0032991; C:protein-containing complex; IDA:RGD.
DR   GO; GO:0045202; C:synapse; IBA:GO_Central.
DR   GO; GO:0097060; C:synaptic membrane; EXP:UniProtKB.
DR   GO; GO:0022848; F:acetylcholine-gated monoatomic cation-selective channel activity; ISS:UniProtKB.
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:0095500; P:acetylcholine receptor signaling pathway; ISO:RGD.
DR   GO; GO:0035095; P:behavioral response to nicotine; ISS:UniProtKB.
DR   GO; GO:0006816; P:calcium ion transport; IBA:GO_Central.
DR   GO; GO:0051899; P:membrane depolarization; ISO:RGD.
DR   GO; GO:0034220; P:monoatomic ion transmembrane transport; IBA:GO_Central.
DR   GO; GO:0007274; P:neuromuscular synaptic transmission; IBA:GO_Central.
DR   GO; GO:0099171; P:presynaptic modulation of chemical synaptic transmission; ISO:RGD.
DR   GO; GO:0014059; P:regulation of dopamine secretion; ISS:UniProtKB.
DR   GO; GO:0035094; P:response to nicotine; IBA:GO_Central.
DR   GO; GO:0007271; P:synaptic transmission, cholinergic; IBA:GO_Central.
DR   CDD; cd19064; LGIC_TM_nAChR; 1.
DR   FunFam; 2.70.170.10:FF:000008; Cholinergic receptor nicotinic alpha 6 subunit; 1.
DR   FunFam; 1.20.58.390:FF:000017; Neuronal acetylcholine receptor subunit alpha-3; 1.
DR   FunFam; 1.20.58.390:FF:000001; Neuronal nicotinic acetylcholine receptor subunit 3; 1.
DR   Gene3D; 2.70.170.10; Neurotransmitter-gated ion-channel ligand-binding domain; 1.
DR   Gene3D; 1.20.58.390; Neurotransmitter-gated ion-channel transmembrane domain; 2.
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   NCBIfam; TIGR00860; LIC; 1.
DR   PANTHER; PTHR18945; NEUROTRANSMITTER GATED ION CHANNEL; 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; SSF90112; Neurotransmitter-gated ion-channel transmembrane pore; 1.
DR   SUPFAM; SSF63712; Nicotinic receptor ligand binding domain-like; 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; Phosphoprotein; Receptor;
KW   Reference proteome; Signal; Synapse; Transmembrane; Transmembrane helix;
KW   Transport.
FT   SIGNAL          1..30
FT                   /evidence="ECO:0000250"
FT   CHAIN           31..493
FT                   /note="Neuronal acetylcholine receptor subunit alpha-6"
FT                   /id="PRO_0000000363"
FT   TOPO_DOM        31..240
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        241..265
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..464
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        465..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"
SQ   SEQUENCE   493 AA;  56947 MW;  A829FAF8FFB060FE CRC64;
     MLNGWGRGDL RSGLCLWICG FLAFFKGSRG CVSEEQLFHT LFAHYNRFIR PVENVSDPVT
     VHFELAITQL ANVDEVNQIM ETNLWLRHVW KDYRLCWDPT EYDGIETLRV PADNIWKPDI
     VLYNNAVGDF QVEGKTKALL KYDGVITWTP PAIFKSSCPM DITFFPFDHQ NCSLKFGSWT
     YDKAEIDLLI IGSKVDMNDF WENSEWEIVD ASGYKHDIKY NCCEEIYTDI TYSFYIRRLP
     MFYTINLIIP CLFISFLTVL VFYLPSDCGE KVTLCISVLL SLTVFLLVIT ETIPSTSLVI
     PLVGEYLLFT MIFVTLSIVV TVFVLNIHYR TPATHTMPKW VKTMFLQVFP SILMMRRPLD
     KTKEMDGVKD PKTHTKRPAK VKFTHRKEPK LLKECRHCHK SSEIAPGKRL SQQPAQWVTE
     NSEHPPDVED VIDSVQFIAE NMKSHNETKE VEDDWKYMAM VVDRVFLWVF IIVCVFGTVG
     LFLQPLLGNT GAS
//