ACHA4_RAT
ID ACHA4_RAT Reviewed; 630 AA.
AC P09483; O35769;
DT 01-JUL-1989, integrated into UniProtKB/Swiss-Prot.
DT 30-MAY-2000, sequence version 3.
DT 03-AUG-2022, entry version 189.
DE RecName: Full=Neuronal acetylcholine receptor subunit alpha-4;
DE Flags: Precursor;
GN Name=Chrna4; Synonyms=Acra4;
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] (ISOFORM ALPHA-4-1), AND NUCLEOTIDE SEQUENCE
RP [MRNA] OF 5-630 (ISOFORM ALPHA-4-2).
RC STRAIN=Sprague-Dawley; TISSUE=Hippocampus, and Hypothalamus;
RX PubMed=3829125; DOI=10.1016/0092-8674(87)90705-7;
RA Goldman D.J., Deneris E.S., Luyten W., Kochhar A., Patrick J.,
RA Heinemann S.F.;
RT "Members of a nicotinic acetylcholine receptor gene family are expressed in
RT different regions of the mammalian central nervous system.";
RL Cell 48:965-973(1987).
RN [2]
RP SEQUENCE REVISION.
RA Hartley M., Goldman D.J., Heinemann S.F.;
RL Submitted (DEC-1998) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM ALPHA-4-2).
RA Boulter J., Deneris E.S., Evans K., Heinemann S.F.;
RL Submitted (JUN-1997) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP PROTEIN SEQUENCE OF 31-47.
RX PubMed=3609304; DOI=10.1016/0014-5793(87)80272-7;
RA Whiting P., Esch F., Shimasaki S., Lindstrom J.;
RT "Neuronal nicotinic acetylcholine receptor beta-subunit is coded for by the
RT cDNA clone alpha 4.";
RL FEBS Lett. 219:459-463(1987).
RN [5]
RP SUBUNIT.
RX PubMed=15929983; DOI=10.1074/jbc.m504229200;
RA Dutertre S., Nicke A., Lewis R.J.;
RT "Beta2 subunit contribution to 4/7 alpha-conotoxin binding to the nicotinic
RT acetylcholine receptor.";
RL J. Biol. Chem. 280:30460-30468(2005).
RN [6]
RP PALMITOYLATION AT CYS-273, AND SUBCELLULAR LOCATION.
RX PubMed=22593584; DOI=10.1074/jbc.m111.328294;
RA Amici S.A., McKay S.B., Wells G.B., Robson J.I., Nasir M., Ponath G.,
RA Anand R.;
RT "A highly conserved cytoplasmic cysteine residue in the alpha4 nicotinic
RT acetylcholine receptor is palmitoylated and regulates protein expression.";
RL J. Biol. Chem. 287:23119-23127(2012).
RN [7]
RP MUTAGENESIS OF 219-THR--ARG-242; 220-TYR--ARG-223 AND ARG-223.
RX PubMed=22751014; DOI=10.1096/fj.12-204487;
RA Kim H.W., McIntosh J.M.;
RT "alpha6 nAChR subunit residues that confer alpha-conotoxin BuIA
RT selectivity.";
RL FASEB J. 26:4102-4110(2012).
RN [8]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-428, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22673903; DOI=10.1038/ncomms1871;
RA Lundby A., Secher A., Lage K., Nordsborg N.B., Dmytriyev A., Lundby C.,
RA Olsen J.V.;
RT "Quantitative maps of protein phosphorylation sites across 14 different rat
RT organs and tissues.";
RL Nat. Commun. 3:876-876(2012).
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 permeable to sodium ions.
CC -!- SUBUNIT: Neuronal AChR is composed of two different types of subunits:
CC alpha and beta. Alpha-4 subunit can be combined to beta-2 or beta-4 to
CC give rise to functional receptors, complexes with beta-2 may be
CC heteropentamers. Interacts with RIC3; which is required for proper
CC folding and assembly. Interacts with LYPD6. The heteropentamer alpha-4-
CC beta-2 interacts with alpha-conotoxins PnIA, GID and MII
CC (PubMed:15929983). {ECO:0000250|UniProtKB:P43681,
CC ECO:0000269|PubMed:15929983}.
CC -!- INTERACTION:
CC P09483; P20420: Chrna5; NbExp=6; IntAct=EBI-7842410, EBI-10828372;
CC P09483; P12390: Chrnb2; NbExp=6; IntAct=EBI-7842410, EBI-9008812;
CC P09483; P12392: Chrnb4; NbExp=4; IntAct=EBI-7842410, EBI-9008856;
CC -!- SUBCELLULAR LOCATION: Postsynaptic cell membrane
CC {ECO:0000269|PubMed:22593584}; Multi-pass membrane protein
CC {ECO:0000269|PubMed:22593584}. Cell membrane
CC {ECO:0000269|PubMed:22593584}; Multi-pass membrane protein
CC {ECO:0000269|PubMed:22593584}. Cell membrane
CC {ECO:0000269|PubMed:22593584}; Lipid-anchor
CC {ECO:0000269|PubMed:22593584}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=Alpha-4-1;
CC IsoId=P09483-1; Sequence=Displayed;
CC Name=Alpha-4-2;
CC IsoId=P09483-2; Sequence=VSP_000074;
CC -!- TISSUE SPECIFICITY: In various regions of the central nervous system.
CC -!- MISCELLANEOUS: The nAChR composed of alpha-4 and beta-2 subunits does
CC not bind the conotoxin BuIA. {ECO:0000269|PubMed:22751014}.
CC -!- SIMILARITY: Belongs to the ligand-gated ion channel (TC 1.A.9) family.
CC Acetylcholine receptor (TC 1.A.9.1) subfamily. Alpha-4/CHRNA4 sub-
CC subfamily. {ECO:0000305}.
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DR EMBL; M15682; AAA41676.1; -; mRNA.
DR EMBL; L31620; AAC97071.1; -; mRNA.
DR EMBL; AF007212; AAB64439.1; -; mRNA.
DR RefSeq; NP_077330.1; NM_024354.1.
DR AlphaFoldDB; P09483; -.
DR SMR; P09483; -.
DR ComplexPortal; CPX-170; Neuronal nicotinic acetylcholine receptor complex, 2xalpha4-3xbeta2.
DR ComplexPortal; CPX-171; Neuronal nicotinic acetylcholine receptor complex, 3xalpha4-2xbeta2.
DR ComplexPortal; CPX-215; Neuronal nicotinic acetylcholine receptor complex, alpha4-alpha5-beta2.
DR ComplexPortal; CPX-219; Neuronal nicotinic acetylcholine receptor complex, alpha4-beta4.
DR CORUM; P09483; -.
DR IntAct; P09483; 6.
DR MINT; P09483; -.
DR STRING; 10116.ENSRNOP00000009041; -.
DR BindingDB; P09483; -.
DR ChEMBL; CHEMBL307; -.
DR DrugCentral; P09483; -.
DR GuidetoPHARMACOLOGY; 465; -.
DR GlyGen; P09483; 3 sites.
DR iPTMnet; P09483; -.
DR PhosphoSitePlus; P09483; -.
DR SwissPalm; P09483; -.
DR PaxDb; P09483; -.
DR PRIDE; P09483; -.
DR GeneID; 25590; -.
DR KEGG; rno:25590; -.
DR UCSC; RGD:2346; rat. [P09483-1]
DR CTD; 1137; -.
DR RGD; 2346; Chrna4.
DR eggNOG; KOG3645; Eukaryota.
DR InParanoid; P09483; -.
DR OrthoDB; 381858at2759; -.
DR PhylomeDB; P09483; -.
DR Reactome; R-RNO-629587; Highly sodium permeable postsynaptic acetylcholine nicotinic receptors.
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:P09483; -.
DR Proteomes; UP000002494; Unplaced.
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:0030425; C:dendrite; IDA:RGD.
DR GO; GO:0098691; C:dopaminergic synapse; ISO:RGD.
DR GO; GO:0009897; C:external side of plasma membrane; ISO:RGD.
DR GO; GO:0005887; C:integral component of plasma membrane; IBA:GO_Central.
DR GO; GO:0099060; C:integral component of postsynaptic specialization membrane; IDA:SynGO.
DR GO; GO:0099056; C:integral component of presynaptic membrane; IDA:SynGO.
DR GO; GO:0016020; C:membrane; IDA:RGD.
DR GO; GO:0043005; C:neuron projection; IBA:GO_Central.
DR GO; GO:0043025; C:neuronal cell body; IDA:RGD.
DR GO; GO:0005886; C:plasma membrane; ISO:RGD.
DR GO; GO:0032991; C:protein-containing complex; IDA:RGD.
DR GO; GO:0045202; C:synapse; IBA:GO_Central.
DR GO; GO:0042166; F:acetylcholine binding; IDA:RGD.
DR GO; GO:0015464; F:acetylcholine receptor activity; ISO:RGD.
DR GO; GO:0022848; F:acetylcholine-gated cation-selective channel activity; IDA:RGD.
DR GO; GO:0005231; F:excitatory extracellular ligand-gated ion channel activity; IBA:GO_Central.
DR GO; GO:0005216; F:ion channel activity; ISO:RGD.
DR GO; GO:0030594; F:neurotransmitter receptor activity; IBA:GO_Central.
DR GO; GO:0044877; F:protein-containing complex binding; IDA:RGD.
DR GO; GO:0050997; F:quaternary ammonium group binding; IDA:RGD.
DR GO; GO:1904315; F:transmitter-gated ion channel activity involved in regulation of postsynaptic membrane potential; IDA:SynGO.
DR GO; GO:0095500; P:acetylcholine receptor signaling pathway; ISO:RGD.
DR GO; GO:0001508; P:action potential; ISO:RGD.
DR GO; GO:0042113; P:B cell activation; ISO:RGD.
DR GO; GO:0035095; P:behavioral response to nicotine; ISO:RGD.
DR GO; GO:0006816; P:calcium ion transport; ISO:RGD.
DR GO; GO:0007268; P:chemical synaptic transmission; IBA:GO_Central.
DR GO; GO:0050890; P:cognition; ISO:RGD.
DR GO; GO:0006281; P:DNA repair; ISO:RGD.
DR GO; GO:0035640; P:exploration behavior; ISO:RGD.
DR GO; GO:0060080; P:inhibitory postsynaptic potential; ISO:RGD.
DR GO; GO:0034220; P:ion transmembrane transport; IBA:GO_Central.
DR GO; GO:0007626; P:locomotory behavior; ISO:RGD.
DR GO; GO:0051899; P:membrane depolarization; ISO:RGD.
DR GO; GO:0050877; P:nervous system process; ISO:RGD.
DR GO; GO:1903048; P:regulation of acetylcholine-gated cation channel activity; IMP:RGD.
DR GO; GO:0014059; P:regulation of dopamine secretion; ISO:RGD.
DR GO; GO:0042391; P:regulation of membrane potential; ISO:RGD.
DR GO; GO:2000300; P:regulation of synaptic vesicle exocytosis; ISO:RGD.
DR GO; GO:0007585; P:respiratory gaseous exchange by respiratory system; ISO:RGD.
DR GO; GO:1905144; P:response to acetylcholine; IDA:RGD.
DR GO; GO:0001666; P:response to hypoxia; ISO:RGD.
DR GO; GO:0035094; P:response to nicotine; ISO:RGD.
DR GO; GO:0006979; P:response to oxidative stress; ISO:RGD.
DR GO; GO:0019233; P:sensory perception of pain; ISO:RGD.
DR GO; GO:0007165; P:signal transduction; ISO:RGD.
DR GO; GO:0007271; P:synaptic transmission, cholinergic; IMP:RGD.
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; Direct protein sequencing;
KW Disulfide bond; Glycoprotein; Ion channel; Ion transport;
KW Ligand-gated ion channel; Lipoprotein; Membrane; Palmitate; Phosphoprotein;
KW Postsynaptic cell membrane; Receptor; Reference proteome; Signal; Synapse;
KW Transmembrane; Transmembrane helix; Transport.
FT SIGNAL 1..30
FT /evidence="ECO:0000255"
FT CHAIN 31..630
FT /note="Neuronal acetylcholine receptor subunit alpha-4"
FT /id="PRO_0000000354"
FT TOPO_DOM 32..249
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 250..270
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 279..299
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 313..333
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 334..604
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 605..625
FT /note="Helical"
FT /evidence="ECO:0000255"
FT REGION 418..463
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 505..526
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 428
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 542
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O70174"
FT MOD_RES 545
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O70174"
FT LIPID 273
FT /note="S-palmitoyl cysteine"
FT /evidence="ECO:0000269|PubMed:22593584"
FT CARBOHYD 59
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 109
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 176
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 163..177
FT /evidence="ECO:0000250"
FT DISULFID 227..228
FT /note="Associated with receptor activation"
FT /evidence="ECO:0000250"
FT VAR_SEQ 629..630
FT /note="AC -> GMI (in isoform Alpha-4-2)"
FT /evidence="ECO:0000303|PubMed:3829125, ECO:0000303|Ref.3"
FT /id="VSP_000074"
FT MUTAGEN 219..240
FT /note="TYNTRKYECCAEIYPDITYAFI->YKHDIKYNCCEEIYTDITYSFY:
FT >10000-fold increase in inhibition of alpha-4-beta-2 nAChR
FT by the conotoxin BuIA."
FT /evidence="ECO:0000269|PubMed:22751014"
FT MUTAGEN 220..223
FT /note="YNTR->KHDI: >1700-fold increase in inhibition of
FT alpha-4-beta-2 nAChR by the conotoxin BuIA."
FT /evidence="ECO:0000269|PubMed:22751014"
FT MUTAGEN 223
FT /note="R->I: >10-fold increase in inhibition of alpha-4-
FT beta-2 nAChR by the conotoxin BuIA."
FT /evidence="ECO:0000269|PubMed:22751014"
FT CONFLICT 1..4
FT /note="MANS -> MEIGGPGA (in Ref. 1; AAA41676)"
FT /evidence="ECO:0000305"
FT CONFLICT 6
FT /note="T -> P (in Ref. 3; AAB64439)"
FT /evidence="ECO:0000305"
FT CONFLICT 58
FT /note="A -> G (in Ref. 1; AAA41676 and 3; AAB64439)"
FT /evidence="ECO:0000305"
FT CONFLICT 196
FT /note="M -> I (in Ref. 1; AAA41676 and 3; AAB64439)"
FT /evidence="ECO:0000305"
FT CONFLICT 301
FT /note="Missing (in Ref. 1; AAA41676/AAC97071 and 3;
FT AAB64439)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 630 AA; 70193 MW; 1DFFC9E1378E5417 CRC64;
MANSGTGAPP PLLLLPLLLL LGTGLLPASS HIETRAHAEE RLLKRLFSGY NKWSRPVANI
SDVVLVRFGL SIAQLIDVDE KNQMMTTNVW VKQEWHDYKL RWDPGDYENV TSIRIPSELI
WRPDIVLYNN ADGDFAVTHL TKAHLFYDGR VQWTPPAIYK SSCSIDVTFF PFDQQNCTMK
FGSWTYDKAK IDLVSMHSRV DQLDFWESGE WVIVDAVGTY NTRKYECCAE IYPDITYAFI
IRRLPLFYTI NLIIPCLLIS CLTVLVFYLP SECGEKVTLC ISVLLSLTVF LLLITEIIPS
PTSLVIPLIG EYLLFTMIFV TLSIVITVFV LNVHHRSPRT HTMPAWVRRV FLDIVPRLLF
MKRPSVVKDN CRRLIESMHK MANAPRFWPE PVGEPGILSD ICNQGLSPAP TFCNPTDTAV
ETQPTCRSPP LEVPDLKTSE VEKASPCPSP GSCPPPKSSS GAPMLIKARS LSVQHVPSSQ
EAAEDGIRCR SRSIQYCVSQ DGAASLADSK PTSSPTSLKA RPSQLPVSDQ ASPCKCTCKE
PSPVSPVTVL KAGGTKAPPQ HLPLSPALTR AVEGVQYIAD HLKAEDTDFS VKEDWKYVAM
VIDRIFLWMF IIVCLLGTVG LFLPPWLAAC
