ACHA_HUMAN
ID ACHA_HUMAN Reviewed; 457 AA.
AC P02708; B4DRV6; D3DPE8;
DT 21-JUL-1986, integrated into UniProtKB/Swiss-Prot.
DT 25-MAY-2022, sequence version 3.
DT 03-AUG-2022, entry version 229.
DE RecName: Full=Acetylcholine receptor subunit alpha;
DE Flags: Precursor;
GN Name=CHRNA1; Synonyms=ACHRA, CHNRA;
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 [GENOMIC DNA].
RX PubMed=6688857; DOI=10.1038/305818a0;
RA Noda M., Furutani Y., Takahashi H., Toyosato M., Tanabe T., Shimizu S.,
RA Kikyotani S., Kayano T., Hirose T., Inayama S., Numa S.;
RT "Cloning and sequence analysis of calf cDNA and human genomic DNA encoding
RT alpha-subunit precursor of muscle acetylcholine receptor.";
RL Nature 305:818-823(1983).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RX PubMed=3338555; DOI=10.1016/0014-5793(88)81430-3;
RA Schoepfer R., Luther M., Lindstrom J.M.;
RT "The human medulloblastoma cell line TE671 expresses a muscle-like
RT acetylcholine receptor. Cloning of the alpha-subunit cDNA.";
RL FEBS Lett. 226:235-240(1988).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND ALTERNATIVE SPLICING (ISOFORM 2).
RC TISSUE=Muscle;
RX PubMed=1694127; DOI=10.1002/j.1460-2075.1990.tb07378.x;
RA Beeson D., Morris A., Vincent A., Newsom-Davis J.;
RT "The human muscle nicotinic acetylcholine receptor alpha-subunit exist as
RT two isoforms: a novel exon.";
RL EMBO J. 9:2101-2106(1990).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RC TISSUE=Thymus;
RX PubMed=7725386;
RA Gattenloehner S., Brabletz T., Schultz A., Marx A.,
RA Mueller-Hermelink H.-K., Kirchner T.;
RT "Cloning of a cDNA coding for the acetylcholine receptor alpha-subunit from
RT a thymoma associated with myasthenia gravis.";
RL Thymus 23:103-113(1994).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Tongue;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP PROTEIN SEQUENCE OF 21-457 (ISOFORM 1).
RX PubMed=2449458; DOI=10.1172/jci113369;
RA Hohlfeld R., Toyka K.V., Miner L.L., Walgrave S.L., Conti-Tronconi B.M.;
RT "Amphipathic segment of the nicotinic receptor alpha subunit contains
RT epitopes recognized by T lymphocytes in myasthenia gravis.";
RL J. Clin. Invest. 81:657-660(1988).
RN [8]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 79-89.
RX PubMed=8441631; DOI=10.1093/nar/21.2.233;
RA Talib S., Okarma T.B., Lebkowski J.S.;
RT "Differential expression of human nicotinic acetylcholine receptor alpha
RT subunit variants in muscle and non-muscle tissues.";
RL Nucleic Acids Res. 21:233-237(1993).
RN [9]
RP FUNCTION (ISOFORMS 1 AND 2), SUBUNIT (ISOFORMS 1 AND 2), MISCELLANEOUS
RP (ISOFORM 2), AND MUTAGENESIS OF GLU-261.
RX PubMed=8788941; DOI=10.1113/jphysiol.1995.sp021090;
RA Newland C.F., Beeson D., Vincent A., Newsom-Davis J.;
RT "Functional and non-functional isoforms of the human muscle acetylcholine
RT receptor.";
RL J. Physiol. (Lond.) 489:767-778(1995).
RN [10]
RP SUBUNIT.
RX PubMed=15609996; DOI=10.1021/bi048918g;
RA Ellison M., Gao F., Wang H.L., Sine S.M., McIntosh J.M., Olivera B.M.;
RT "Alpha-conotoxins ImI and ImII target distinct regions of the human alpha7
RT nicotinic acetylcholine receptor and distinguish human nicotinic receptor
RT subtypes.";
RL Biochemistry 43:16019-16026(2004).
RN [11]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Leukemic T-cell;
RX PubMed=19690332; DOI=10.1126/scisignal.2000007;
RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K.,
RA Rodionov V., Han D.K.;
RT "Quantitative phosphoproteomic analysis of T cell receptor signaling
RT reveals system-wide modulation of protein-protein interactions.";
RL Sci. Signal. 2:RA46-RA46(2009).
RN [12]
RP FUNCTION, SUBCELLULAR LOCATION, AND MUTAGENESIS OF VAL-275.
RX PubMed=27375219; DOI=10.1002/humu.23043;
RA Shen X.M., Okuno T., Milone M., Otsuka K., Takahashi K., Komaki H.,
RA Giles E., Ohno K., Engel A.G.;
RT "Mutations causing slow-channel myasthenia reveal that a valine ring in the
RT channel pore of muscle AChR is optimized for stabilizing channel gating.";
RL Hum. Mutat. 37:1051-1059(2016).
RN [13]
RP VARIANT CMS1A SER-173.
RX PubMed=7619526; DOI=10.1016/0896-6273(95)90080-2;
RA Sine S.M., Ohno K., Bouzat C., Auerbach A., Milone M., Pruitt J.N. II,
RA Engel A.G.;
RT "Mutation of the acetylcholine receptor alpha subunit causes a slow-channel
RT myasthenic syndrome by enhancing agonist binding affinity.";
RL Neuron 15:229-239(1995).
RN [14]
RP VARIANT CMS1A LYS-237.
RX PubMed=8872460; DOI=10.1093/hmg/5.9.1217;
RA Engel A.G., Ohno K., Milone M., Wang H.-L., Nakano S., Bouzat C.,
RA Pruitt J.N. II, Hutchinson D.O., Brengman J.M., Bren N., Sieb J.P.,
RA Sine S.M.;
RT "New mutations in acetylcholine receptor subunit genes reveal heterogeneity
RT in the slow-channel congenital myasthenic syndrome.";
RL Hum. Mol. Genet. 5:1217-1227(1996).
RN [15]
RP VARIANTS CMS1A SER-173; MET-176; ILE-274 AND ILE-289.
RX PubMed=9158151; DOI=10.1093/hmg/6.5.767;
RA Croxen R., Newland C., Beeson D., Oosterhuis H., Chauplannaz G.,
RA Vincent A., Newsom-Davis J.;
RT "Mutations in different functional domains of the human muscle
RT acetylcholine receptor alpha subunit in patients with the slow-channel
RT congenital myasthenic syndrome.";
RL Hum. Mol. Genet. 6:767-774(1997).
RN [16]
RP VARIANT CMS1A PHE-269, AND CHARACTERIZATION OF VARIANT CMS1A PHE-269.
RX PubMed=9221765; DOI=10.1523/jneurosci.17-15-05651.1997;
RA Milone M., Wang H.-L., Ohno K., Fukudome T., Pruitt J.N. II, Bren N.,
RA Sine S.M., Engel A.G.;
RT "Slow-channel myasthenic syndrome caused by enhanced activation,
RT desensitization, and agonist binding affinity attributable to mutation in
RT the M2 domain of the acetylcholine receptor alpha subunit.";
RL J. Neurosci. 17:5651-5665(1997).
RN [17]
RP VARIANTS CMS1B VAL-253 AND ILE-305, AND CHARACTERIZATION OF VARIANTS CMS1B
RP VAL-253 AND ILE-305.
RX PubMed=10195214; DOI=10.1038/6326;
RA Wang H.-L., Milone M., Ohno K., Shen X.-M., Tsujino A., Batocchi A.-P.,
RA Tonali P., Brengman J., Engel A.G., Sine S.M.;
RT "Acetylcholine receptor M3 domain: stereochemical and volume contributions
RT to channel gating.";
RL Nat. Neurosci. 2:226-233(1999).
RN [18]
RP ERRATUM OF PUBMED:10195214.
RA Wang H.-L., Milone M., Ohno K., Shen X.-M., Tsujino A., Batocchi A.-P.,
RA Tonali P., Brengman J., Engel A.G., Sine S.M.;
RL Nat. Neurosci. 2:485-485(1999).
RN [19]
RP VARIANT CMS1B LEU-152, AND CHARACTERIZATION OF VARIANT CMS1B LEU-152.
RX PubMed=12588888; DOI=10.1172/jci200316997;
RA Shen X.-M., Ohno K., Tsujino A., Brengman J.M., Gingold M., Sine S.M.,
RA Engel A.G.;
RT "Mutation causing severe myasthenia reveals functional asymmetry of AChR
RT signature cystine loops in agonist binding and gating.";
RL J. Clin. Invest. 111:497-505(2003).
RN [20]
RP VARIANT CMS1B LEU-276, AND CHARACTERIZATION OF VARIANT CMS1B LEU-276.
RX PubMed=15079006; DOI=10.1212/01.wnl.0000118205.99701.41;
RA Webster R., Brydson M., Croxen R., Newsom-Davis J., Vincent A., Beeson D.;
RT "Mutation in the AChR ion channel gate underlies a fast channel congenital
RT myasthenic syndrome.";
RL Neurology 62:1090-1096(2004).
RN [21]
RP VARIANT CMS1A TRP-438, AND CHARACTERIZATION OF VARIANT CMS1A TRP-438.
RX PubMed=16685696; DOI=10.1002/ana.20861;
RA Shen X.-M., Deymeer F., Sine S.M., Engel A.G.;
RT "Slow-channel mutation in acetylcholine receptor alphaM4 domain and its
RT efficient knockdown.";
RL Ann. Neurol. 60:128-136(2006).
RN [22]
RP VARIANT LMPS LEU-229.
RX PubMed=18252226; DOI=10.1016/j.ajhg.2007.11.006;
RA Michalk A., Stricker S., Becker J., Rupps R., Pantzar T., Miertus J.,
RA Botta G., Naretto V.G., Janetzki C., Yaqoob N., Ott C.-E., Seelow D.,
RA Wieczorek D., Fiebig B., Wirth B., Hoopmann M., Walther M., Koerber F.,
RA Blankenburg M., Mundlos S., Heller R., Hoffmann K.;
RT "Acetylcholine receptor pathway mutations explain various fetal akinesia
RT deformation sequence disorders.";
RL Am. J. Hum. Genet. 82:464-476(2008).
CC -!- FUNCTION: [Isoform 1]: Upon acetylcholine binding, the AChR responds by
CC an extensive change in conformation that affects all subunits and leads
CC to opening of an ion-conducting channel across the plasma membrane.
CC {ECO:0000269|PubMed:27375219}.
CC -!- FUNCTION: [Isoform 2]: Non functional acetylcholine receptor alpha
CC subunit which is not integrated into functional acetylcholine-gated
CC cation-selective channels. {ECO:0000269|PubMed:8788941}.
CC -!- SUBUNIT: [Isoform 1]: One of the alpha chains that assemble within the
CC acetylcholine receptor, a pentamer of two alpha chains, a beta, a
CC delta, and a gamma (in immature muscle) or epsilon (in mature muscle)
CC chains. The muscle heteropentamer composed of alpha-1, beta-1, delta,
CC epsilon subunits interacts with the alpha-conotoxin ImII
CC (PubMed:15609996). {ECO:0000269|PubMed:15609996}.
CC -!- SUBUNIT: [Isoform 2]: Is able to interact with other subunits of the
CC acetylcholine receptor but is not assembled into functional
CC acetylcholine-gated cation-selective channels.
CC {ECO:0000269|PubMed:8788941}.
CC -!- SUBCELLULAR LOCATION: Postsynaptic cell membrane
CC {ECO:0000305|PubMed:27375219}; Multi-pass membrane protein
CC {ECO:0000255}. Cell membrane {ECO:0000269|PubMed:27375219}; Multi-pass
CC membrane protein {ECO:0000255}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=P02708-2; Sequence=Displayed;
CC Name=2; Synonyms=P3A(+), alpha+ {ECO:0000303|PubMed:8788941};
CC IsoId=P02708-1; Sequence=VSP_061499;
CC -!- TISSUE SPECIFICITY: Isoform 1 is only expressed in skeletal muscle.
CC Isoform 2 is constitutively expressed in skeletal muscle, brain, heart,
CC kidney, liver, lung and thymus.
CC -!- DISEASE: Multiple pterygium syndrome, lethal type (LMPS) [MIM:253290]:
CC Multiple pterygia are found infrequently in children with
CC arthrogryposis and in fetuses with fetal akinesia syndrome. In lethal
CC multiple pterygium syndrome there is intrauterine growth retardation,
CC multiple pterygia, and flexion contractures causing severe
CC arthrogryposis and fetal akinesia. Subcutaneous edema can be severe,
CC causing fetal hydrops with cystic hygroma and lung hypoplasia.
CC Oligohydramnios and facial anomalies are frequent.
CC {ECO:0000269|PubMed:18252226}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- DISEASE: Note=The alpha subunit is the main focus for antibody binding
CC in myasthenia gravis. Myasthenia gravis is characterized by sporadic
CC muscular fatigability and weakness, occurring chiefly in muscles
CC innervated by cranial nerves, and characteristically improved by
CC cholinesterase-inhibiting drugs.
CC -!- DISEASE: Myasthenic syndrome, congenital, 1A, slow-channel (CMS1A)
CC [MIM:601462]: A common congenital myasthenic syndrome. Congenital
CC myasthenic syndromes are characterized by muscle weakness affecting the
CC axial and limb muscles (with hypotonia in early-onset forms), the
CC ocular muscles (leading to ptosis and ophthalmoplegia), and the facial
CC and bulbar musculature (affecting sucking and swallowing, and leading
CC to dysphonia). The symptoms fluctuate and worsen with physical effort.
CC CMS1A is a slow-channel myasthenic syndrome. It is caused by kinetic
CC abnormalities of the AChR, resulting in prolonged AChR channel opening
CC episodes, prolonged endplate currents, and depolarization block. This
CC is associated with calcium overload, which may contribute to subsequent
CC degeneration of the endplate and postsynaptic membrane.
CC {ECO:0000269|PubMed:16685696, ECO:0000269|PubMed:7619526,
CC ECO:0000269|PubMed:8872460, ECO:0000269|PubMed:9158151,
CC ECO:0000269|PubMed:9221765}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- DISEASE: Myasthenic syndrome, congenital, 1B, fast-channel (CMS1B)
CC [MIM:608930]: A form of congenital myasthenic syndrome, a group of
CC disorders characterized by failure of neuromuscular transmission,
CC including pre-synaptic, synaptic, and post-synaptic disorders that are
CC not of autoimmune origin. Clinical features are easy fatigability and
CC muscle weakness affecting the axial and limb muscles (with hypotonia in
CC early-onset forms), the ocular muscles (leading to ptosis and
CC ophthalmoplegia), and the facial and bulbar musculature (affecting
CC sucking and swallowing, and leading to dysphonia). The symptoms
CC fluctuate and worsen with physical effort. CMS1B is a fast-channel
CC myasthenic syndrome. It is caused by kinetic abnormalities of the AChR,
CC resulting in brief opening and activity of the channel, with a rapid
CC decay in endplate current, failure to achieve threshold depolarization
CC of the endplate and consequent failure to fire an action potential.
CC {ECO:0000269|PubMed:10195214, ECO:0000269|PubMed:12588888,
CC ECO:0000269|PubMed:15079006}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- MISCELLANEOUS: [Isoform 2]: Acetylcholine receptors incorporating that
CC alpha subunit do not bind alpha-bungarotoxin.
CC {ECO:0000269|PubMed:8788941}.
CC -!- SIMILARITY: Belongs to the ligand-gated ion channel (TC 1.A.9) family.
CC Acetylcholine receptor (TC 1.A.9.1) subfamily. Alpha-1/CHRNA1 sub-
CC subfamily. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=CAA49705.1; Type=Frameshift; Evidence={ECO:0000305};
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DR EMBL; X02502; CAA26344.1; -; Genomic_DNA.
DR EMBL; X02503; CAA26344.1; JOINED; Genomic_DNA.
DR EMBL; X02504; CAA26344.1; JOINED; Genomic_DNA.
DR EMBL; X02505; CAA26344.1; JOINED; Genomic_DNA.
DR EMBL; X02506; CAA26344.1; JOINED; Genomic_DNA.
DR EMBL; X02507; CAA26344.1; JOINED; Genomic_DNA.
DR EMBL; X02508; CAA26344.1; JOINED; Genomic_DNA.
DR EMBL; Y00762; CAA68731.1; -; mRNA.
DR EMBL; X17104; CAA34960.1; -; Genomic_DNA.
DR EMBL; AK299445; BAG61418.1; -; mRNA.
DR EMBL; CH471058; EAX11125.1; -; Genomic_DNA.
DR EMBL; CH471058; EAX11127.1; -; Genomic_DNA.
DR EMBL; S77094; AAD14247.1; -; mRNA.
DR EMBL; X70108; CAA49705.1; ALT_FRAME; Genomic_DNA.
DR CCDS; CCDS2261.1; -. [P02708-2]
DR CCDS; CCDS33331.1; -. [P02708-2]
DR PIR; A03168; ACHUA1.
DR PIR; S10148; S10148.
DR RefSeq; NP_000070.1; NM_000079.3. [P02708-2]
DR RefSeq; NP_001034612.1; NM_001039523.2. [P02708-1]
DR PDB; 4ZJS; X-ray; 2.23 A; A/B/C/D/E=21-50, A/B/C/D/E=81-101.
DR PDB; 5HBT; X-ray; 2.61 A; B=21-231.
DR PDBsum; 4ZJS; -.
DR PDBsum; 5HBT; -.
DR AlphaFoldDB; P02708; -.
DR SMR; P02708; -.
DR BioGRID; 107556; 45.
DR ComplexPortal; CPX-2179; Muscle-type nicotinic acetylcholine receptor complex, alpha1-beta1-delta-gamma.
DR ComplexPortal; CPX-255; Muscle-type nicotinic acetylcholine receptor complex, alpha1-beta1-delta-epsilon.
DR IntAct; P02708; 3.
DR STRING; 9606.ENSP00000261007; -.
DR BindingDB; P02708; -.
DR ChEMBL; CHEMBL4808; -.
DR DrugBank; DB08838; Agmatine.
DR DrugBank; DB00555; Lamotrigine.
DR DrugCentral; P02708; -.
DR GuidetoPHARMACOLOGY; 462; -.
DR TCDB; 1.A.9.1.1; the neurotransmitter receptor, cys loop, ligand-gated ion channel (lic) family.
DR GlyGen; P02708; 1 site.
DR iPTMnet; P02708; -.
DR PhosphoSitePlus; P02708; -.
DR BioMuta; CHRNA1; -.
DR DMDM; 113071; -.
DR MassIVE; P02708; -.
DR PaxDb; P02708; -.
DR PeptideAtlas; P02708; -.
DR PRIDE; P02708; -.
DR ABCD; P02708; 38 sequenced antibodies.
DR Antibodypedia; 19487; 440 antibodies from 37 providers.
DR DNASU; 1134; -.
DR Ensembl; ENST00000261007.9; ENSP00000261007.5; ENSG00000138435.16. [P02708-1]
DR Ensembl; ENST00000348749.9; ENSP00000261008.5; ENSG00000138435.16. [P02708-2]
DR GeneID; 1134; -.
DR KEGG; hsa:1134; -.
DR MANE-Select; ENST00000348749.9; ENSP00000261008.5; NM_000079.4; NP_000070.1.
DR UCSC; uc002ujd.3; human. [P02708-2]
DR CTD; 1134; -.
DR DisGeNET; 1134; -.
DR GeneCards; CHRNA1; -.
DR GeneReviews; CHRNA1; -.
DR HGNC; HGNC:1955; CHRNA1.
DR HPA; ENSG00000138435; Tissue enriched (skeletal).
DR MalaCards; CHRNA1; -.
DR MIM; 100690; gene.
DR MIM; 253290; phenotype.
DR MIM; 254200; phenotype.
DR MIM; 601462; phenotype.
DR MIM; 608930; phenotype.
DR neXtProt; NX_P02708; -.
DR OpenTargets; ENSG00000138435; -.
DR Orphanet; 33108; Lethal multiple pterygium syndrome.
DR Orphanet; 98913; Postsynaptic congenital myasthenic syndromes.
DR PharmGKB; PA26487; -.
DR VEuPathDB; HostDB:ENSG00000138435; -.
DR eggNOG; KOG3645; Eukaryota.
DR GeneTree; ENSGT00940000156851; -.
DR HOGENOM; CLU_018074_1_0_1; -.
DR InParanoid; P02708; -.
DR OMA; STHIMPE; -.
DR OrthoDB; 381858at2759; -.
DR PhylomeDB; P02708; -.
DR TreeFam; TF315605; -.
DR PathwayCommons; P02708; -.
DR Reactome; R-HSA-629594; Highly calcium permeable postsynaptic nicotinic acetylcholine receptors.
DR Reactome; R-HSA-629597; Highly calcium permeable nicotinic acetylcholine receptors.
DR SignaLink; P02708; -.
DR SIGNOR; P02708; -.
DR BioGRID-ORCS; 1134; 8 hits in 1073 CRISPR screens.
DR GeneWiki; Cholinergic_receptor,_nicotinic,_alpha_1; -.
DR GenomeRNAi; 1134; -.
DR Pharos; P02708; Tclin.
DR PRO; PR:P02708; -.
DR Proteomes; UP000005640; Chromosome 2.
DR RNAct; P02708; protein.
DR Bgee; ENSG00000138435; Expressed in gastrocnemius and 101 other tissues.
DR ExpressionAtlas; P02708; baseline and differential.
DR Genevisible; P02708; HS.
DR GO; GO:0005892; C:acetylcholine-gated channel complex; ISS:BHF-UCL.
DR GO; GO:0070161; C:anchoring junction; IEA:UniProtKB-KW.
DR GO; GO:0009986; C:cell surface; IDA:BHF-UCL.
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:0031594; C:neuromuscular junction; IDA:MGI.
DR GO; GO:0043005; C:neuron projection; IBA:GO_Central.
DR GO; GO:0005886; C:plasma membrane; IDA:HPA.
DR GO; GO:0045211; C:postsynaptic membrane; NAS:BHF-UCL.
DR GO; GO:0045202; C:synapse; IBA:GO_Central.
DR GO; GO:0042166; F:acetylcholine binding; IEA:Ensembl.
DR GO; GO:0015464; F:acetylcholine receptor activity; TAS:ProtInc.
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:0005216; F:ion channel activity; TAS:ProtInc.
DR GO; GO:0030594; F:neurotransmitter receptor activity; IBA:GO_Central.
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; IC:ComplexPortal.
DR GO; GO:0007268; P:chemical synaptic transmission; IBA:GO_Central.
DR GO; GO:0034220; P:ion transmembrane transport; IBA:GO_Central.
DR GO; GO:0046716; P:muscle cell cellular homeostasis; IMP:BHF-UCL.
DR GO; GO:0050881; P:musculoskeletal movement; IMP:BHF-UCL.
DR GO; GO:0050877; P:nervous system process; IBA:GO_Central.
DR GO; GO:0007528; P:neuromuscular junction development; IMP:MGI.
DR GO; GO:0050905; P:neuromuscular process; IMP:BHF-UCL.
DR GO; GO:0007274; P:neuromuscular synaptic transmission; IMP:MGI.
DR GO; GO:0070050; P:neuron cellular homeostasis; IMP:BHF-UCL.
DR GO; GO:0019228; P:neuronal action potential; IMP:BHF-UCL.
DR GO; GO:0042391; P:regulation of membrane potential; IMP:BHF-UCL.
DR GO; GO:0007165; P:signal transduction; IBA:GO_Central.
DR GO; GO:0003009; P:skeletal muscle contraction; IMP:BHF-UCL.
DR GO; GO:0048630; P:skeletal muscle tissue growth; IMP:BHF-UCL.
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; 2.
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 3D-structure; Alternative splicing; Cell membrane;
KW Congenital myasthenic syndrome; Direct protein sequencing; Disease variant;
KW Disulfide bond; Glycoprotein; Ion channel; Ion transport;
KW Ligand-gated ion channel; Membrane; Postsynaptic cell membrane; Receptor;
KW Reference proteome; Signal; Synapse; Transmembrane; Transmembrane helix;
KW Transport.
FT SIGNAL 1..20
FT /evidence="ECO:0000269|PubMed:2449458"
FT CHAIN 21..457
FT /note="Acetylcholine receptor subunit alpha"
FT /id="PRO_0000000305"
FT TOPO_DOM 21..232
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 233..253
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 254..264
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 265..285
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 286..296
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 297..317
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 318..427
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 428..448
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 449..457
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT CARBOHYD 161
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 148..162
FT DISULFID 212..213
FT /note="Associated with receptor activation"
FT VAR_SEQ 78
FT /note="Q -> QGDMVDLPRPSCVTLGVPLFSHLQNE (in isoform 2)"
FT /id="VSP_061499"
FT VARIANT 152
FT /note="V -> L (in CMS1B; mutant channel shows an
FT approximately 30-fold decrease of ACh binding affinity for
FT the second of 2 closed-state binding sites but only a 2-
FT fold decrease in gating efficiency; dbSNP:rs137852807)"
FT /evidence="ECO:0000269|PubMed:12588888"
FT /id="VAR_038599"
FT VARIANT 173
FT /note="G -> S (in CMS1A; dbSNP:rs137852801)"
FT /evidence="ECO:0000269|PubMed:7619526,
FT ECO:0000269|PubMed:9158151"
FT /id="VAR_000282"
FT VARIANT 176
FT /note="V -> M (in CMS1A; dbSNP:rs137852799)"
FT /evidence="ECO:0000269|PubMed:9158151"
FT /id="VAR_000283"
FT VARIANT 229
FT /note="R -> L (in LMPS; dbSNP:rs137852809)"
FT /evidence="ECO:0000269|PubMed:18252226"
FT /id="VAR_043904"
FT VARIANT 237
FT /note="N -> K (in CMS1A; dbSNP:rs137852798)"
FT /evidence="ECO:0000269|PubMed:8872460"
FT /id="VAR_000284"
FT VARIANT 253
FT /note="F -> V (in CMS1B; markedly reduced protein
FT expression; dbSNP:rs137852805)"
FT /evidence="ECO:0000269|PubMed:10195214"
FT /id="VAR_021206"
FT VARIANT 269
FT /note="V -> F (in CMS1A; causes increased channel opening
FT in absence of ACh; prolonged opening in presence of ACh;
FT increased affinity for ACh and enhanced desensitization;
FT dbSNP:rs137852803)"
FT /evidence="ECO:0000269|PubMed:9221765"
FT /id="VAR_021207"
FT VARIANT 274
FT /note="T -> I (in CMS1A; dbSNP:rs137852800)"
FT /evidence="ECO:0000269|PubMed:9158151"
FT /id="VAR_000285"
FT VARIANT 276
FT /note="F -> L (in CMS1B; fewer and shorter ion channel
FT activations with decreased channel opening rate and
FT increased channel closing rate; dbSNP:rs137852806)"
FT /evidence="ECO:0000269|PubMed:15079006"
FT /id="VAR_021208"
FT VARIANT 289
FT /note="S -> I (in CMS1A; dbSNP:rs137852802)"
FT /evidence="ECO:0000269|PubMed:9158151"
FT /id="VAR_000286"
FT VARIANT 305
FT /note="V -> I (in CMS1B; abnormally slow channel opening
FT and closing resulting in abnormally brief current;
FT dbSNP:rs137852804)"
FT /evidence="ECO:0000269|PubMed:10195214"
FT /id="VAR_021209"
FT VARIANT 358
FT /note="D -> V (in dbSNP:rs6739001)"
FT /id="VAR_038600"
FT VARIANT 438
FT /note="C -> W (in CMS1A; increases the rate of channel
FT opening and slows the rate of channel closing but has no
FT effect on agonist binding; dbSNP:rs137852808)"
FT /evidence="ECO:0000269|PubMed:16685696"
FT /id="VAR_038601"
FT MUTAGEN 261
FT /note="E->Q: Changed acetylcholine-gated cation-selective
FT channel activity."
FT /evidence="ECO:0000269|PubMed:8788941"
FT MUTAGEN 275
FT /note="V->A: Increased length of channel opening."
FT /evidence="ECO:0000269|PubMed:27375219"
FT CONFLICT 390
FT /note="P -> F (in Ref. 4; AAD14247)"
FT /evidence="ECO:0000305"
FT HELIX 23..31
FT /evidence="ECO:0007829|PDB:4ZJS"
FT STRAND 37..39
FT /evidence="ECO:0007829|PDB:5HBT"
FT STRAND 49..52
FT /evidence="ECO:0007829|PDB:4ZJS"
FT TURN 65..68
FT /evidence="ECO:0007829|PDB:5HBT"
FT STRAND 69..78
FT /evidence="ECO:0007829|PDB:5HBT"
FT STRAND 106..111
FT /evidence="ECO:0007829|PDB:4ZJS"
FT HELIX 114..117
FT /evidence="ECO:0007829|PDB:4ZJS"
FT STRAND 122..126
FT /evidence="ECO:0007829|PDB:4ZJS"
FT HELIX 127..129
FT /evidence="ECO:0007829|PDB:5HBT"
FT STRAND 135..138
FT /evidence="ECO:0007829|PDB:5HBT"
FT STRAND 140..145
FT /evidence="ECO:0007829|PDB:5HBT"
FT STRAND 152..156
FT /evidence="ECO:0007829|PDB:5HBT"
FT STRAND 159..163
FT /evidence="ECO:0007829|PDB:5HBT"
FT STRAND 166..172
FT /evidence="ECO:0007829|PDB:5HBT"
FT STRAND 184..195
FT /evidence="ECO:0007829|PDB:5HBT"
FT TURN 198..200
FT /evidence="ECO:0007829|PDB:5HBT"
FT STRAND 201..209
FT /evidence="ECO:0007829|PDB:5HBT"
FT STRAND 219..235
FT /evidence="ECO:0007829|PDB:5HBT"
FT STRAND 243..254
FT /evidence="ECO:0007829|PDB:5HBT"
SQ SEQUENCE 457 AA; 51839 MW; 89480567D85C15B8 CRC64;
MEPWPLLLLF SLCSAGLVLG SEHETRLVAK LFKDYSSVVR PVEDHRQVVE VTVGLQLIQL
INVDEVNQIV TTNVRLKQQW VDYNLKWNPD DYGGVKKIHI PSEKIWRPDL VLYNNADGDF
AIVKFTKVLL QYTGHITWTP PAIFKSYCEI IVTHFPFDEQ NCSMKLGTWT YDGSVVAINP
ESDQPDLSNF MESGEWVIKE SRGWKHSVTY SCCPDTPYLD ITYHFVMQRL PLYFIVNVII
PCLLFSFLTG LVFYLPTDSG EKMTLSISVL LSLTVFLLVI VELIPSTSSA VPLIGKYMLF
TMVFVIASII ITVIVINTHH RSPSTHVMPN WVRKVFIDTI PNIMFFSTMK RPSREKQDKK
IFTEDIDISD ISGKPGPPPM GFHSPLIKHP EVKSAIEGIK YIAETMKSDQ ESNNAAAEWK
YVAMVMDHIL LGVFMLVCII GTLAVFAGRL IELNQQG
