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 27-MAR-2024, entry version 190. 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}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- 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 EMDB; EMD-10691; -. DR EMDB; EMD-10692; -. DR EMDB; EMD-10693; -. 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 GlyCosmos; O70174; 3 sites, No reported glycans. DR GlyGen; O70174; 3 sites. DR iPTMnet; O70174; -. DR PhosphoSitePlus; O70174; -. DR PaxDb; 10090-ENSMUSP00000066338; -. DR ProteomicsDB; 285540; -. DR Antibodypedia; 29717; 322 antibodies from 34 providers. DR DNASU; 11438; -. DR Ensembl; ENSMUST00000067120.14; ENSMUSP00000066338.8; ENSMUSG00000027577.15. DR GeneID; 11438; -. DR KEGG; mmu:11438; -. DR UCSC; uc008okq.1; mouse. DR AGR; MGI:87888; -. 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; PRLWSEI; -. DR OrthoDB; 5489962at2759; -. 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 112 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 109 other cell types or tissues. DR ExpressionAtlas; O70174; baseline and differential. DR GO; GO:0005892; C:acetylcholine-gated channel complex; IDA:MGI. 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: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:0099634; C:postsynaptic specialization membrane; ISO:MGI. DR GO; GO:0042734; C:presynaptic membrane; IDA:SynGO. 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; ISO:MGI. DR GO; GO:0022848; F:acetylcholine-gated monoatomic cation-selective channel activity; IMP:MGI. DR GO; GO:1901363; F:heterocyclic compound binding; ISO:MGI. DR GO; GO:0005216; F:monoatomic ion channel activity; IDA:MGI. 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 monoatomic 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: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:0007626; P:locomotory behavior; IMP:MGI. DR GO; GO:0051899; P:membrane depolarization; IMP:MGI. DR GO; GO:0050877; P:nervous system process; IMP:MGI. DR GO; GO:0019228; P:neuronal action potential; IMP:MGI. DR GO; GO:0099171; P:presynaptic modulation of chemical synaptic transmission; IDA:SynGO. 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: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 CDD; cd19064; LGIC_TM_nAChR; 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:SF401; NEURONAL ACETYLCHOLINE RECEPTOR SUBUNIT ALPHA-4; 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. DR Genevisible; O70174; MM. 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 //