Acetylcholine receptor subunit alpha

Details

Name
Acetylcholine receptor subunit alpha
Synonyms
  • ACHRA
  • CHNRA
Gene Name
CHRNA1
Organism
Humans
Amino acid sequence
>lcl|BSEQ0009580|Acetylcholine receptor subunit alpha
MEPWPLLLLFSLCSAGLVLGSEHETRLVAKLFKDYSSVVRPVEDHRQVVEVTVGLQLIQL
INVDEVNQIVTTNVRLKQGDMVDLPRPSCVTLGVPLFSHLQNEQWVDYNLKWNPDDYGGV
KKIHIPSEKIWRPDLVLYNNADGDFAIVKFTKVLLQYTGHITWTPPAIFKSYCEIIVTHF
PFDEQNCSMKLGTWTYDGSVVAINPESDQPDLSNFMESGEWVIKESRGWKHSVTYSCCPD
TPYLDITYHFVMQRLPLYFIVNVIIPCLLFSFLTGLVFYLPTDSGEKMTLSISVLLSLTV
FLLVIVELIPSTSSAVPLIGKYMLFTMVFVIASIIITVIVINTHHRSPSTHVMPNWVRKV
FIDTIPNIMFFSTMKRPSREKQDKKIFTEDIDISDISGKPGPPPMGFHSPLIKHPEVKSA
IEGIKYIAETMKSDQESNNAAAEWKYVAMVMDHILLGVFMLVCIIGTLAVFAGRLIELNQ
QG
Number of residues
482
Molecular Weight
54545.235
Theoretical pI
Not Available
GO Classification
Functions
acetylcholine binding / acetylcholine receptor activity / acetylcholine-activated cation-selective channel activity / ion channel activity
Processes
cation transmembrane transport / ion transmembrane transport / muscle cell cellular homeostasis / musculoskeletal movement / neuromuscular junction development / neuromuscular process / neuromuscular synaptic transmission / neuron cellular homeostasis / neuronal action potential / regulation of membrane potential / response to nicotine / signal transduction / skeletal muscle contraction / skeletal muscle tissue growth / synaptic transmission / synaptic transmission, cholinergic / transport
Components
acetylcholine-gated channel complex / cell junction / cell surface / neuromuscular junction / neuron projection / plasma membrane / postsynaptic membrane
General Function
Ion channel activity
Specific Function
After binding acetylcholine, the AChR responds by an extensive change in conformation that affects all subunits and leads to opening of an ion-conducting channel across the plasma membrane.
Pfam Domain Function
Transmembrane Regions
256-280 288-306 322-341 454-472
Cellular Location
Cell junction
Gene sequence
>lcl|BSEQ0013245|Acetylcholine receptor subunit alpha (CHRNA1)
ATGGAGCCCTGGCCTCTCCTCCTGCTCTTTAGCCTTTGCTCAGCTGGCCTCGTCCTGGGC
TCCGAACATGAGACCCGTCTGGTGGCAAAGCTATTTAAAGACTACAGCAGCGTGGTGCGG
CCAGTGGAAGACCACCGCCAGGTCGTGGAGGTCACCGTGGGCCTGCAGCTGATACAGCTC
ATCAATGTGGATGAAGTAAATCAGATCGTGACAACCAATGTGCGTCTGAAACAGCAATGG
GTGGATTACAACCTAAAATGGAATCCAGATGACTATGGCGGTGTGAAAAAAATTCACATT
CCTTCAGAAAAGATCTGGCGCCCAGACCTTGTTCTCTATAACAATGCAGATGGTGACTTT
GCTATTGTCAAGTTCACCAAAGTGCTCCTGCAGTACACTGGCCACATCACGTGGACACCT
CCAGCCATCTTTAAAAGCTACTGTGAGATCATCGTCACCCACTTTCCCTTTGATGAACAG
AACTGCAGCATGAAGCTGGGCACCTGGACCTACGACGGCTCTGTCGTGGCCATCAACCCG
GAAAGCGACCAGCCAGACCTGAGCAACTTCATGGAGAGCGGGGAGTGGGTGATCAAGGAG
TCCCGGGGCTGGAAGCACTCCGTGACCTATTCCTGCTGCCCCGACACCCCCTACCTGGAC
ATCACCTACCACTTCGTCATGCAGCGCCTGCCCCTCTACTTCATCGTCAACGTCATCATC
CCCTGCCTGCTCTTCTCCTTCTTAACTGGCCTGGTATTCTACCTGCCCACAGACTCAGGG
GAGAAGATGACTCTGAGCATCTCTGTCTTACTGTCTTTGACTGTGTTCCTTCTGGTCATC
GTGGAGCTGATCCCCTCCACGTCCAGTGCTGTGCCCTTGATTGGAAAATACATGCTGTTC
ACCATGGTGTTCGTCATTGCCTCCATCATCATCACTGTCATCGTCATCAACACACACCAC
CGCTCACCCAGCACCCATGTCATGCCCAACTGGGTGCGGAAGGTTTTTATCGACACTATC
CCAAATATCATGTTTTTCTCCACAATGAAAAGACCATCCAGAGAAAAGCAAGACAAAAAG
ATTTTTACAGAAGACATTGATATCTCTGACATTTCTGGAAAGCCAGGGCCTCCACCCATG
GGCTTCCACTCTCCCCTGATCAAACACCCCGAGGTGAAAAGTGCCATCGAGGGCATCAAG
TACATCGCAGAGACCATGAAGTCAGACCAGGAGTCTAACAATGCGGCGGCAGAGTGGAAG
TACGTTGCAATGGTGATGGACCACATACTCCTCGGAGTCTTCATGCTTGTTTGCATCATC
GGAACCCTAGCCGTGTTTGCAGGTCGACTCATTGAATTAAATCAGCAAGGATGA
Chromosome Location
2
Locus
Not Available
External Identifiers
ResourceLink
UniProtKB IDP02708
UniProtKB Entry NameACHA_HUMAN
HGNC IDHGNC:1955
General References
  1. Noda M, Furutani Y, Takahashi H, Toyosato M, Tanabe T, Shimizu S, Kikyotani S, Kayano T, Hirose T, Inayama S, et al.: Cloning and sequence analysis of calf cDNA and human genomic DNA encoding alpha-subunit precursor of muscle acetylcholine receptor. Nature. 1983 Oct 27-Nov 2;305(5937):818-23. [PubMed:6688857]
  2. Schoepfer R, Luther M, Lindstrom J: The human medulloblastoma cell line TE671 expresses a muscle-like acetylcholine receptor. Cloning of the alpha-subunit cDNA. FEBS Lett. 1988 Jan 4;226(2):235-40. [PubMed:3338555]
  3. Beeson D, Morris A, Vincent A, Newsom-Davis J: The human muscle nicotinic acetylcholine receptor alpha-subunit exist as two isoforms: a novel exon. EMBO J. 1990 Jul;9(7):2101-6. [PubMed:1694127]
  4. Gattenlohner S, Brabletz T, Schultz A, Marx A, Muller-Hermelink HK, Kirchner T: Cloning of a cDNA coding for the acetylcholine receptor alpha-subunit from a thymoma associated with myasthenia [correction of myastenia] gravis. Thymus. 1994;23(2):103-13. [PubMed:7725386]
  5. Ota T, Suzuki Y, Nishikawa T, Otsuki T, Sugiyama T, Irie R, Wakamatsu A, Hayashi K, Sato H, Nagai K, Kimura K, Makita H, Sekine M, Obayashi M, Nishi T, Shibahara T, Tanaka T, Ishii S, Yamamoto J, Saito K, Kawai Y, Isono Y, Nakamura Y, Nagahari K, Murakami K, Yasuda T, Iwayanagi T, Wagatsuma M, Shiratori A, Sudo H, Hosoiri T, Kaku Y, Kodaira H, Kondo H, Sugawara M, Takahashi M, Kanda K, Yokoi T, Furuya T, Kikkawa E, Omura Y, Abe K, Kamihara K, Katsuta N, Sato K, Tanikawa M, Yamazaki M, Ninomiya K, Ishibashi T, Yamashita H, Murakawa K, Fujimori K, Tanai H, Kimata M, Watanabe M, Hiraoka S, Chiba Y, Ishida S, Ono Y, Takiguchi S, Watanabe S, Yosida M, Hotuta T, Kusano J, Kanehori K, Takahashi-Fujii A, Hara H, Tanase TO, Nomura Y, Togiya S, Komai F, Hara R, Takeuchi K, Arita M, Imose N, Musashino K, Yuuki H, Oshima A, Sasaki N, Aotsuka S, Yoshikawa Y, Matsunawa H, Ichihara T, Shiohata N, Sano S, Moriya S, Momiyama H, Satoh N, Takami S, Terashima Y, Suzuki O, Nakagawa S, Senoh A, Mizoguchi H, Goto Y, Shimizu F, Wakebe H, Hishigaki H, Watanabe T, Sugiyama A, Takemoto M, Kawakami B, Yamazaki M, Watanabe K, Kumagai A, Itakura S, Fukuzumi Y, Fujimori Y, Komiyama M, Tashiro H, Tanigami A, Fujiwara T, Ono T, Yamada K, Fujii Y, Ozaki K, Hirao M, Ohmori Y, Kawabata A, Hikiji T, Kobatake N, Inagaki H, Ikema Y, Okamoto S, Okitani R, Kawakami T, Noguchi S, Itoh T, Shigeta K, Senba T, Matsumura K, Nakajima Y, Mizuno T, Morinaga M, Sasaki M, Togashi T, Oyama M, Hata H, Watanabe M, Komatsu T, Mizushima-Sugano J, Satoh T, Shirai Y, Takahashi Y, Nakagawa K, Okumura K, Nagase T, Nomura N, Kikuchi H, Masuho Y, Yamashita R, Nakai K, Yada T, Nakamura Y, Ohara O, Isogai T, Sugano S: Complete sequencing and characterization of 21,243 full-length human cDNAs. Nat Genet. 2004 Jan;36(1):40-5. Epub 2003 Dec 21. [PubMed:14702039]
  6. Hohlfeld R, Toyka KV, Miner LL, Walgrave SL, Conti-Tronconi BM: Amphipathic segment of the nicotinic receptor alpha subunit contains epitopes recognized by T lymphocytes in myasthenia gravis. J Clin Invest. 1988 Mar;81(3):657-60. [PubMed:2449458]
  7. Talib S, Okarma TB, Lebkowski JS: Differential expression of human nicotinic acetylcholine receptor alpha subunit variants in muscle and non-muscle tissues. Nucleic Acids Res. 1993 Jan 25;21(2):233-7. [PubMed:8441631]
  8. Mayya V, Lundgren DH, Hwang SI, Rezaul K, Wu L, Eng JK, Rodionov V, Han DK: Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions. Sci Signal. 2009 Aug 18;2(84):ra46. doi: 10.1126/scisignal.2000007. [PubMed:19690332]
  9. Sine SM, Ohno K, Bouzat C, Auerbach A, Milone M, Pruitt JN, Engel AG: Mutation of the acetylcholine receptor alpha subunit causes a slow-channel myasthenic syndrome by enhancing agonist binding affinity. Neuron. 1995 Jul;15(1):229-39. [PubMed:7619526]
  10. Engel AG, Ohno K, Milone M, Wang HL, Nakano S, Bouzat C, Pruitt JN 2nd, Hutchinson DO, Brengman JM, Bren N, Sieb JP, Sine SM: New mutations in acetylcholine receptor subunit genes reveal heterogeneity in the slow-channel congenital myasthenic syndrome. Hum Mol Genet. 1996 Sep;5(9):1217-27. [PubMed:8872460]
  11. Croxen R, Newland C, Beeson D, Oosterhuis H, Chauplannaz G, Vincent A, Newsom-Davis J: Mutations in different functional domains of the human muscle acetylcholine receptor alpha subunit in patients with the slow-channel congenital myasthenic syndrome. Hum Mol Genet. 1997 May;6(5):767-74. [PubMed:9158151]
  12. Milone M, Wang HL, Ohno K, Fukudome T, Pruitt JN, Bren N, Sine SM, Engel AG: Slow-channel myasthenic syndrome caused by enhanced activation, desensitization, and agonist binding affinity attributable to mutation in the M2 domain of the acetylcholine receptor alpha subunit. J Neurosci. 1997 Aug 1;17(15):5651-65. [PubMed:9221765]
  13. Wang HL, Milone M, Ohno K, Shen XM, Tsujino A, Batocchi AP, Tonali P, Brengman J, Engel AG, Sine SM: Acetylcholine receptor M3 domain: stereochemical and volume contributions to channel gating. Nat Neurosci. 1999 Mar;2(3):226-33. [PubMed:10195214]
  14. Shen XM, Ohno K, Tsujino A, Brengman JM, Gingold M, Sine SM, Engel AG: Mutation causing severe myasthenia reveals functional asymmetry of AChR signature cystine loops in agonist binding and gating. J Clin Invest. 2003 Feb;111(4):497-505. [PubMed:12588888]
  15. Webster R, Brydson M, Croxen R, Newsom-Davis J, Vincent A, Beeson D: Mutation in the AChR ion channel gate underlies a fast channel congenital myasthenic syndrome. Neurology. 2004 Apr 13;62(7):1090-6. [PubMed:15079006]
  16. Shen XM, Deymeer F, Sine SM, Engel AG: Slow-channel mutation in acetylcholine receptor alphaM4 domain and its efficient knockdown. Ann Neurol. 2006 Jul;60(1):128-36. [PubMed:16685696]
  17. Michalk A, Stricker S, Becker J, Rupps R, Pantzar T, Miertus J, Botta G, Naretto VG, Janetzki C, Yaqoob N, Ott CE, Seelow D, Wieczorek D, Fiebig B, Wirth B, Hoopmann M, Walther M, Korber F, Blankenburg M, Mundlos S, Heller R, Hoffmann K: Acetylcholine receptor pathway mutations explain various fetal akinesia deformation sequence disorders. Am J Hum Genet. 2008 Feb;82(2):464-76. doi: 10.1016/j.ajhg.2007.11.006. [PubMed:18252226]

Drug Relations

Drug Relations
DrugBank IDNameDrug groupPharmacological action?ActionsDetails
DB08838AgmatineexperimentalyesantagonistDetails
DB00555Lamotrigineapproved, investigationalunknowninhibitorDetails