ACHA4_MOUSE
ID ACHA4_MOUSE Reviewed; 629 AA.
AC O70174; Q8BHE9; Q8VI10; Q9ET51;
DT 15-DEC-1998, integrated into UniProtKB/Swiss-Prot.
DT 19-SEP-2003, sequence version 2.
DT 03-AUG-2022, entry version 181.
DE RecName: Full=Neuronal acetylcholine receptor subunit alpha-4;
DE Flags: Precursor;
GN Name=Chrna4; Synonyms=Acra4;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], AND VARIANT ALA-529.
RC STRAIN=Long sleep selected line;
RX PubMed=11434511; DOI=10.1097/00008571-200106000-00008;
RA Stitzel J.A., Dobelis P., Jimenez M., Collins A.C.;
RT "Long sleep and short sleep mice differ in nicotine-stimulated 86Rb+ efflux
RT and alpha4 nicotinic receptor subunit cDNA sequence.";
RL Pharmacogenetics 11:331-339(2001).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Diencephalon, and Hippocampus;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Brain;
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 [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-27.
RX PubMed=9749753; DOI=10.1046/j.1460-9568.1998.00235.x;
RA Watanabe H., Zoli M., Changeux J.-P.;
RT "Promoter analysis of the neuronal nicotinic acetylcholine receptor alpha4
RT gene: methylation and expression of the transgene.";
RL Eur. J. Neurosci. 10:2244-2253(1998).
RN [5]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 118-357.
RC STRAIN=C57BL/6J;
RA Kuo Y.-P., Lukas R.J.;
RT "Expression of mouse nicotinic acetylcholine receptor genes in the
RT developing thymus.";
RL Submitted (DEC-2000) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-540 AND SER-543, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
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 (By
CC similarity). {ECO:0000250|UniProtKB:P09483,
CC ECO:0000250|UniProtKB:P43681}.
CC -!- INTERACTION:
CC O70174; Q8BLC3: Lypd1; NbExp=3; IntAct=EBI-10916203, EBI-14035010;
CC -!- SUBCELLULAR LOCATION: Postsynaptic cell membrane; Multi-pass membrane
CC protein. Cell membrane; Multi-pass membrane protein. Cell membrane
CC {ECO:0000250}; Lipid-anchor {ECO:0000250}.
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; AF225912; AAF34716.2; -; mRNA.
DR EMBL; AK034228; BAC28638.1; -; mRNA.
DR EMBL; AK083157; BAC38788.1; -; mRNA.
DR EMBL; BC053013; AAH53013.1; -; mRNA.
DR EMBL; AB010002; BAA25752.1; -; Genomic_DNA.
DR EMBL; AF325347; AAL37363.1; -; mRNA.
DR CCDS; CCDS17192.1; -.
DR RefSeq; NP_056545.3; NM_015730.5.
DR AlphaFoldDB; O70174; -.
DR SMR; O70174; -.
DR BioGRID; 197932; 8.
DR ComplexPortal; CPX-167; Neuronal nicotinic acetylcholine receptor complex, 3xalpha4-2xbeta2.
DR ComplexPortal; CPX-169; Neuronal nicotinic acetylcholine receptor complex, 2xalpha4-3xbeta2.
DR ComplexPortal; CPX-216; Neuronal nicotinic acetylcholine receptor complex, alpha4-alpha5-beta2.
DR ComplexPortal; CPX-220; Neuronal nicotinic acetylcholine receptor complex, alpha4-beta4.
DR DIP; DIP-48731N; -.
DR IntAct; O70174; 6.
DR STRING; 10090.ENSMUSP00000066338; -.
DR BindingDB; O70174; -.
DR ChEMBL; CHEMBL4457; -.
DR DrugCentral; O70174; -.
DR GlyGen; O70174; 3 sites.
DR iPTMnet; O70174; -.
DR PhosphoSitePlus; O70174; -.
DR PaxDb; O70174; -.
DR PRIDE; O70174; -.
DR ProteomicsDB; 285540; -.
DR Antibodypedia; 29717; 287 antibodies from 34 providers.
DR DNASU; 11438; -.
DR Ensembl; ENSMUST00000067120; ENSMUSP00000066338; ENSMUSG00000027577.
DR GeneID; 11438; -.
DR KEGG; mmu:11438; -.
DR UCSC; uc008okq.1; mouse.
DR CTD; 1137; -.
DR MGI; MGI:87888; Chrna4.
DR VEuPathDB; HostDB:ENSMUSG00000027577; -.
DR eggNOG; KOG3645; Eukaryota.
DR GeneTree; ENSGT00940000159329; -.
DR HOGENOM; CLU_018074_1_1_1; -.
DR InParanoid; O70174; -.
DR OMA; IFPAFGH; -.
DR OrthoDB; 381858at2759; -.
DR PhylomeDB; O70174; -.
DR TreeFam; TF315605; -.
DR Reactome; R-MMU-629587; Highly sodium permeable postsynaptic acetylcholine nicotinic receptors.
DR Reactome; R-MMU-629594; Highly calcium permeable postsynaptic nicotinic acetylcholine receptors.
DR Reactome; R-MMU-629597; Highly calcium permeable nicotinic acetylcholine receptors.
DR BioGRID-ORCS; 11438; 1 hit in 107 CRISPR screens.
DR ChiTaRS; Chrna4; mouse.
DR PRO; PR:O70174; -.
DR Proteomes; UP000000589; Chromosome 2.
DR RNAct; O70174; protein.
DR Bgee; ENSMUSG00000027577; Expressed in lumbar subsegment of spinal cord and 107 other tissues.
DR ExpressionAtlas; O70174; baseline and differential.
DR Genevisible; O70174; MM.
DR GO; GO:0005892; C:acetylcholine-gated channel complex; IDA:MGI.
DR GO; GO:0070161; C:anchoring junction; IEA:UniProtKB-KW.
DR GO; GO:0098981; C:cholinergic synapse; ISO:MGI.
DR GO; GO:0030425; C:dendrite; ISO:MGI.
DR GO; GO:0098691; C:dopaminergic synapse; IDA:SynGO.
DR GO; GO:0009897; C:external side of plasma membrane; IDA:MGI.
DR GO; GO:0005887; C:integral component of plasma membrane; IBA:GO_Central.
DR GO; GO:0099060; C:integral component of postsynaptic specialization membrane; ISO:MGI.
DR GO; GO:0099056; C:integral component of presynaptic membrane; IDA:SynGO.
DR GO; GO:0016020; C:membrane; IDA:MGI.
DR GO; GO:0043005; C:neuron projection; IBA:GO_Central.
DR GO; GO:0043025; C:neuronal cell body; ISO:MGI.
DR GO; GO:0005886; C:plasma membrane; IDA:MGI.
DR GO; GO:0032991; C:protein-containing complex; ISO:MGI.
DR GO; GO:0045202; C:synapse; IBA:GO_Central.
DR GO; GO:0042166; F:acetylcholine binding; ISO:MGI.
DR GO; GO:0015464; F:acetylcholine receptor activity; IDA:MGI.
DR GO; GO:0022848; F:acetylcholine-gated cation-selective channel activity; IMP:MGI.
DR GO; GO:0005231; F:excitatory extracellular ligand-gated ion channel activity; IBA:GO_Central.
DR GO; GO:1901363; F:heterocyclic compound binding; ISO:MGI.
DR GO; GO:0005216; F:ion channel activity; IDA:MGI.
DR GO; GO:0030594; F:neurotransmitter receptor activity; IBA:GO_Central.
DR GO; GO:0044877; F:protein-containing complex binding; ISO:MGI.
DR GO; GO:0050997; F:quaternary ammonium group binding; ISO:MGI.
DR GO; GO:1904315; F:transmitter-gated ion channel activity involved in regulation of postsynaptic membrane potential; ISO:MGI.
DR GO; GO:0095500; P:acetylcholine receptor signaling pathway; IDA:MGI.
DR GO; GO:0042113; P:B cell activation; IMP:MGI.
DR GO; GO:0035095; P:behavioral response to nicotine; IMP:MGI.
DR GO; GO:0006816; P:calcium ion transport; IGI:MGI.
DR GO; GO:0007268; P:chemical synaptic transmission; IBA:GO_Central.
DR GO; GO:0050890; P:cognition; ISO:MGI.
DR GO; GO:0006281; P:DNA repair; ISO:MGI.
DR GO; GO:0035640; P:exploration behavior; IMP:MGI.
DR GO; GO:0060080; P:inhibitory postsynaptic potential; IMP:MGI.
DR GO; GO:0034220; P:ion transmembrane transport; IBA:GO_Central.
DR GO; GO:0007626; P:locomotory behavior; IMP:MGI.
DR GO; GO:0051899; P:membrane depolarization; IDA:ComplexPortal.
DR GO; GO:0050877; P:nervous system process; IMP:MGI.
DR GO; GO:0019228; P:neuronal action potential; IMP:MGI.
DR GO; GO:1903048; P:regulation of acetylcholine-gated cation channel activity; ISO:MGI.
DR GO; GO:0014059; P:regulation of dopamine secretion; IMP:MGI.
DR GO; GO:0042391; P:regulation of membrane potential; IGI:MGI.
DR GO; GO:2000300; P:regulation of synaptic vesicle exocytosis; IDA:SynGO.
DR GO; GO:0007585; P:respiratory gaseous exchange by respiratory system; IMP:MGI.
DR GO; GO:1905144; P:response to acetylcholine; ISO:MGI.
DR GO; GO:0001666; P:response to hypoxia; ISO:MGI.
DR GO; GO:0035094; P:response to nicotine; IDA:MGI.
DR GO; GO:0006979; P:response to oxidative stress; ISO:MGI.
DR GO; GO:0019233; P:sensory perception of pain; IMP:MGI.
DR GO; GO:0007165; P:signal transduction; ISO:MGI.
DR GO; GO:0007271; P:synaptic transmission, cholinergic; IDA:MGI.
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 Cell membrane; 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..629
FT /note="Neuronal acetylcholine receptor subunit alpha-4"
FT /id="PRO_0000000352"
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 312..332
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 333..603
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 604..624
FT /note="Helical"
FT /evidence="ECO:0000255"
FT REGION 420..459
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 503..529
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 427
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P09483"
FT MOD_RES 540
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 543
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT LIPID 273
FT /note="S-palmitoyl cysteine"
FT /evidence="ECO:0000250"
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 VARIANT 529
FT /note="T -> A"
FT /evidence="ECO:0000269|PubMed:11434511"
FT CONFLICT 16
FT /note="P -> L (in Ref. 1; AAF34716)"
FT /evidence="ECO:0000305"
FT CONFLICT 24
FT /note="G -> A (in Ref. 4; BAA25752)"
FT /evidence="ECO:0000305"
FT CONFLICT 134
FT /note="D -> N (in Ref. 1; AAF34716)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 629 AA; 70305 MW; 261455B6ED50B41C CRC64;
MEIGGSGAPP 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
TSLVIPLIGE YLLFTMIFVT LSIVITVFVL NVHHRSPRTH TMPAWVRRVF LDIVPRLLFM
KRPSVVKDNC RRLIESMHKM ANAPRFWPEP ESEPGILGDI CNQGLSPAPT FCNRMDTAVE
TQPTCRSPSH KVPDLKTSEV EKASPCPSPG SCHPPNSSGA PVLIKARSLS VQHVPSSQEA
AEGSIRCRSR SIQYCVSQDG AASLTESKPT GSPASLKTRP SQLPVSDQTS PCKCTCKEPS
PVSPITVLKA GGTKAPPQHL PLSPALTRAV EGVQYIADHL KAEDTDFSVK EDWKYVAMVI
DRIFLWMFII VCLLGTVGLF LPPWLAGMI
