Neuronal acetylcholine receptor subunit alpha-4

Details

Name
Neuronal acetylcholine receptor subunit alpha-4
Synonyms
  • NACRA4
Gene Name
CHRNA4
Organism
Humans
Amino acid sequence
>lcl|BSEQ0001694|Neuronal acetylcholine receptor subunit alpha-4
MELGGPGAPRLLPPLLLLLGTGLLRASSHVETRAHAEERLLKKLFSGYNKWSRPVANISD
VVLVRFGLSIAQLIDVDEKNQMMTTNVWVKQEWHDYKLRWDPADYENVTSIRIPSELIWR
PDIVLYNNADGDFAVTHLTKAHLFHDGRVQWTPPAIYKSSCSIDVTFFPFDQQNCTMKFG
SWTYDKAKIDLVNMHSRVDQLDFWESGEWVIVDAVGTYNTRKYECCAEIYPDITYAFVIR
RLPLFYTINLIIPCLLISCLTVLVFYLPSECGEKITLCISVLLSLTVFLLLITEIIPSTS
LVIPLIGEYLLFTMIFVTLSIVITVFVLNVHHRSPRTHTMPTWVRRVFLDIVPRLLLMKR
PSVVKDNCRRLIESMHKMASAPRFWPEPEGEPPATSGTQSLHPPSPSFCVPLDVPAEPGP
SCKSPSDQLPPQQPLEAEKASPHPSPGPCRPPHGTQAPGLAKARSLSVQHMSSPGEAVEG
GVRCRSRSIQYCVPRDDAAPEADGQAAGALASRNTHSAELPPPDQPSPCKCTCKKEPSSV
SPSATVKTRSTKAPPPHLPLSPALTRAVEGVQYIADHLKAEDTDFSVKEDWKYVAMVIDR
IFLWMFIIVCLLGTVGLFLPPWLAGMI
Number of residues
627
Molecular Weight
69956.47
Theoretical pI
7.21
GO Classification
Functions
acetylcholine binding / acetylcholine receptor activity / acetylcholine-activated cation-selective channel activity / ligand-gated ion channel activity
Processes
action potential / B cell activation / behavioral response to nicotine / calcium ion transport / cation transmembrane transport / cognition / DNA repair / exploration behavior / inhibitory postsynaptic potential / ion transmembrane transport / ion transport / locomotory behavior / membrane depolarization / neurological system process / neuromuscular synaptic transmission / regulation of dopamine secretion / regulation of membrane potential / respiratory gaseous exchange / response to hypoxia / response to nicotine / response to oxidative stress / sensory perception of pain / signal transduction / synaptic transmission / synaptic transmission, cholinergic
Components
acetylcholine-gated channel complex / cell junction / dendrite / external side of plasma membrane / integral component of membrane / membrane / neuron projection / neuronal cell body / plasma membrane / postsynaptic membrane / synapse
General Function
Ligand-gated 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 permeable to sodium ions.
Pfam Domain Function
Transmembrane Regions
243-267 275-293 309-330 601-619
Cellular Location
Cell junction
Gene sequence
>lcl|BSEQ0016224|Neuronal acetylcholine receptor subunit alpha-4 (CHRNA4)
ATGGAGCTAGGGGGCCCCGGAGCGCCGCGGCTGCTGCCGCCGCTGCTGCTGCTTCTGGGG
ACCGGCCTCCTGCGCGCCAGCAGCCATGTGGAGACCCGGGCCCACGCCGAGGAGCGGCTC
CTGAAGAAACTCTTCTCCGGTTACAACAAGTGGTCCCGACCCGTGGCCAACATCTCGGAC
GTGGTCCTCGTCCGCTTCGGCCTGTCCATCGCTCAGCTCATTGACGTGGATGAGAAGAAC
CAGATGATGACCACGAACGTATGGGTGAAGCAGGAGTGGCACGACTACAAGCTGCGCTGG
GACCCAGCTGACTATGAGAATGTCACCTCCATCCGCATCCCCTCCGAGCTCATCTGGCGG
CCGGACATCGTCCTCTACAACAATGCTGACGGGGACTTCGCGGTCACCCACCTGACCAAG
GCCCACCTGTTCCATGACGGGCGGGTGCAGTGGACTCCCCCGGCCATTTACAAGAGCTCC
TGCAGCATCGACGTCACCTTCTTCCCCTTCGACCAGCAGAACTGCACCATGAAATTCGGC
TCCTGGACCTACGACAAGGCCAAGATCGACCTGGTGAACATGCACAGCCGCGTGGACCAG
CTGGACTTCTGGGAGAGTGGCGAGTGGGTCATCGTGGATGCCGTGGGCACCTACAACACC
AGGAAGTACGAGTGCTGTGCCGAGATCTACCCGGACATCACCTATGCCTTCGTCATCCGG
CGGCTGCCGCTCTTCTACACCATCAACCTCATCATCCCCTGCCTGCTCATCTCCTGCCTC
ACCGTGCTGGTCTTCTACCTGCCCTCCGAGTGTGGCGAGAAGATCACGCTGTGCATCTCC
GTGCTGCTGTCGCTCACCGTCTTCCTGCTGCTCATCACCGAGATCATCCCGTCCACCTCA
CTGGTCATCCCACTCATCGGCGAGTACCTGCTGTTCACCATGATCTTCGTCACCCTGTCC
ATCGTCATCACGGTCTTCGTGCTCAACGTGCACCACCGCTCGCCACGCACGCACACCATG
CCCACCTGGGTACGCAGGGTCTTCCTGGACATCGTGCCACGCCTGCTCCTCATGAAGCGG
CCGTCCGTGGTCAAGGACAATTGCCGGCGGCTCATCGAGTCCATGCATAAGATGGCCAGT
GCCCCGCGCTTCTGGCCCGAGCCAGAAGGGGAGCCCCCTGCCACGAGCGGCACCCAGAGC
CTGCACCCGCCCTCACCGTCCTTCTGTGTCCCCCTGGATGTGCCGGCTGAGCCTGGGCCT
TCCTGCAAGTCACCCTCCGACCAGCTCCCTCCTCAGCAGCCCCTGGAAGCTGAGAAAGCC
AGCCCCCACCCCTCGCCTGGACCCTGCCGCCCGCCCCACGGCACCCAGGCACCAGGGCTG
GCCAAAGCCAGGTCCCTCAGCGTCCAGCACATGTCCAGCCCTGGCGAAGCGGTGGAAGGC
GGCGTCCGGTGCCGGTCTCGGAGCATCCAGTACTGTGTTCCCCGAGACGATGCCGCCCCC
GAGGCAGATGGCCAGGCTGCCGGCGCCCTGGCCTCTCGCAACACCCACTCGGCTGAGCTC
CCACCCCCAGACCAGCCCTCTCCGTGCAAATGCACATGCAAGAAGGAGCCCTCTTCGGTG
TCCCCGAGCGCCACGGTCAAGACCCGCAGCACCAAAGCGCCGCCCCCGCACCTGCCCCTG
TCGCCGGCCCTGACCCGGGCGGTGGAGGGCGTCCAGTACATTGCAGACCACCTGAAGGCC
GAAGACACAGACTTCTCGGTGAAGGAGGACTGGAAGTACGTGGCCATGGTCATCGACCGC
ATCTTCCTCTGGATGTTCATCATCGTCTGCCTGCTGGGGACGGTGGGCCTCTTCCTGCCG
CCCTGGCTGGCTGGCATGATCTAG
Chromosome Location
20
Locus
20q13.2-q13.3
External Identifiers
ResourceLink
UniProtKB IDP43681
UniProtKB Entry NameACHA4_HUMAN
GenBank Protein ID755648
GenBank Gene IDL35901
GenAtlas IDCHRNA4
HGNC IDHGNC:1958
General References
  1. Monteggia LM, Gopalakrishnan M, Touma E, Idler KB, Nash N, Arneric SP, Sullivan JP, Giordano T: Cloning and transient expression of genes encoding the human alpha 4 and beta 2 neuronal nicotinic acetylcholine receptor (nAChR) subunits. Gene. 1995 Apr 3;155(2):189-93. [PubMed:7721089]
  2. Steinlein O, Weiland S, Stoodt J, Propping P: Exon-intron structure of the human neuronal nicotinic acetylcholine receptor alpha 4 subunit (CHRNA4). Genomics. 1996 Mar 1;32(2):289-94. [PubMed:8833159]
  3. Elliott KJ, Ellis SB, Berckhan KJ, Urrutia A, Chavez-Noriega LE, Johnson EC, Velicelebi G, Harpold MM: Comparative structure of human neuronal alpha 2-alpha 7 and beta 2-beta 4 nicotinic acetylcholine receptor subunits and functional expression of the alpha 2, alpha 3, alpha 4, alpha 7, beta 2, and beta 4 subunits. J Mol Neurosci. 1996 Fall;7(3):217-28. [PubMed:8906617]
  4. Groot Kormelink PJ, Luyten WH: Cloning and sequence of full-length cDNAs encoding the human neuronal nicotinic acetylcholine receptor (nAChR) subunits beta3 and beta4 and expression of seven nAChR subunits in the human neuroblastoma cell line SH-SY5Y and/or IMR-32. FEBS Lett. 1997 Jan 6;400(3):309-14. [PubMed:9009220]
  5. Deloukas P, Matthews LH, Ashurst J, Burton J, Gilbert JG, Jones M, Stavrides G, Almeida JP, Babbage AK, Bagguley CL, Bailey J, Barlow KF, Bates KN, Beard LM, Beare DM, Beasley OP, Bird CP, Blakey SE, Bridgeman AM, Brown AJ, Buck D, Burrill W, Butler AP, Carder C, Carter NP, Chapman JC, Clamp M, Clark G, Clark LN, Clark SY, Clee CM, Clegg S, Cobley VE, Collier RE, Connor R, Corby NR, Coulson A, Coville GJ, Deadman R, Dhami P, Dunn M, Ellington AG, Frankland JA, Fraser A, French L, Garner P, Grafham DV, Griffiths C, Griffiths MN, Gwilliam R, Hall RE, Hammond S, Harley JL, Heath PD, Ho S, Holden JL, Howden PJ, Huckle E, Hunt AR, Hunt SE, Jekosch K, Johnson CM, Johnson D, Kay MP, Kimberley AM, King A, Knights A, Laird GK, Lawlor S, Lehvaslaiho MH, Leversha M, Lloyd C, Lloyd DM, Lovell JD, Marsh VL, Martin SL, McConnachie LJ, McLay K, McMurray AA, Milne S, Mistry D, Moore MJ, Mullikin JC, Nickerson T, Oliver K, Parker A, Patel R, Pearce TA, Peck AI, Phillimore BJ, Prathalingam SR, Plumb RW, Ramsay H, Rice CM, Ross MT, Scott CE, Sehra HK, Shownkeen R, Sims S, Skuce CD, Smith ML, Soderlund C, Steward CA, Sulston JE, Swann M, Sycamore N, Taylor R, Tee L, Thomas DW, Thorpe A, Tracey A, Tromans AC, Vaudin M, Wall M, Wallis JM, Whitehead SL, Whittaker P, Willey DL, Williams L, Williams SA, Wilming L, Wray PW, Hubbard T, Durbin RM, Bentley DR, Beck S, Rogers J: The DNA sequence and comparative analysis of human chromosome 20. Nature. 2001 Dec 20-27;414(6866):865-71. [PubMed:11780052]
  6. Gerhard DS, Wagner L, Feingold EA, Shenmen CM, Grouse LH, Schuler G, Klein SL, Old S, Rasooly R, Good P, Guyer M, Peck AM, Derge JG, Lipman D, Collins FS, Jang W, Sherry S, Feolo M, Misquitta L, Lee E, Rotmistrovsky K, Greenhut SF, Schaefer CF, Buetow K, Bonner TI, Haussler D, Kent J, Kiekhaus M, Furey T, Brent M, Prange C, Schreiber K, Shapiro N, Bhat NK, Hopkins RF, Hsie F, Driscoll T, Soares MB, Casavant TL, Scheetz TE, Brown-stein MJ, Usdin TB, Toshiyuki S, Carninci P, Piao Y, Dudekula DB, Ko MS, Kawakami K, Suzuki Y, Sugano S, Gruber CE, Smith MR, Simmons B, Moore T, Waterman R, Johnson SL, Ruan Y, Wei CL, Mathavan S, Gunaratne PH, Wu J, Garcia AM, Hulyk SW, Fuh E, Yuan Y, Sneed A, Kowis C, Hodgson A, Muzny DM, McPherson J, Gibbs RA, Fahey J, Helton E, Ketteman M, Madan A, Rodrigues S, Sanchez A, Whiting M, Madari A, Young AC, Wetherby KD, Granite SJ, Kwong PN, Brinkley CP, Pearson RL, Bouffard GG, Blakesly RW, Green ED, Dickson MC, Rodriguez AC, Grimwood J, Schmutz J, Myers RM, Butterfield YS, Griffith M, Griffith OL, Krzywinski MI, Liao N, Morin R, Palmquist D, Petrescu AS, Skalska U, Smailus DE, Stott JM, Schnerch A, Schein JE, Jones SJ, Holt RA, Baross A, Marra MA, Clifton S, Makowski KA, Bosak S, Malek J: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. 2004 Oct;14(10B):2121-7. [PubMed:15489334]
  7. Lansdell SJ, Gee VJ, Harkness PC, Doward AI, Baker ER, Gibb AJ, Millar NS: RIC-3 enhances functional expression of multiple nicotinic acetylcholine receptor subtypes in mammalian cells. Mol Pharmacol. 2005 Nov;68(5):1431-8. Epub 2005 Aug 24. [PubMed:16120769]
  8. Bondarenko V, Mowrey D, Tillman T, Cui T, Liu LT, Xu Y, Tang P: NMR structures of the transmembrane domains of the alpha4beta2 nAChR. Biochim Biophys Acta. 2012 May;1818(5):1261-8. doi: 10.1016/j.bbamem.2012.02.008. Epub 2012 Feb 14. [PubMed:22361591]
  9. Steinlein OK, Mulley JC, Propping P, Wallace RH, Phillips HA, Sutherland GR, Scheffer IE, Berkovic SF: A missense mutation in the neuronal nicotinic acetylcholine receptor alpha 4 subunit is associated with autosomal dominant nocturnal frontal lobe epilepsy. Nat Genet. 1995 Oct;11(2):201-3. [PubMed:7550350]
  10. Hirose S, Iwata H, Akiyoshi H, Kobayashi K, Ito M, Wada K, Kaneko S, Mitsudome A: A novel mutation of CHRNA4 responsible for autosomal dominant nocturnal frontal lobe epilepsy. Neurology. 1999 Nov 10;53(8):1749-53. [PubMed:10563623]
  11. Cho YW, Motamedi GK, Laufenberg I, Sohn SI, Lim JG, Lee H, Yi SD, Lee JH, Kim DK, Reba R, Gaillard WD, Theodore WH, Lesser RP, Steinlein OK: A Korean kindred with autosomal dominant nocturnal frontal lobe epilepsy and mental retardation. Arch Neurol. 2003 Nov;60(11):1625-32. [PubMed:14623738]

Drug Relations

Drug Relations
DrugBank IDNameDrug groupPharmacological action?ActionsDetails
DB01273Vareniclineapproved, investigationalyespartial agonistDetails
DB00184NicotineapprovedyesagonistDetails
DB05458PozaniclineinvestigationalunknownDetails
DB05740RPI-78MinvestigationalunknownDetails
DB01351Amobarbitalapproved, illicitunknownantagonistDetails
DB00312Pentobarbitalapproved, investigational, vet_approvedunknownantagonistDetails
DB00237Butabarbitalapproved, illicitunknownantagonistDetails
DB00241Butalbitalapproved, illicitunknownantagonistDetails
DB00306Talbutalapproved, illicitunknownantagonistDetails
DB00418Secobarbitalapproved, vet_approvedunknownantagonistDetails
DB00463MetharbitalwithdrawnunknownantagonistDetails
DB00599Thiopentalapproved, vet_approvedunknownantagonistDetails
DB00794Primidoneapproved, vet_approvedunknownantagonistDetails
DB00849MethylphenobarbitalapprovedunknownantagonistDetails
DB01174Phenobarbitalapproved, investigationalunknownantagonistDetails
DB01352Aprobarbitalexperimental, illicitunknownantagonistDetails
DB01353Butobarbitalapproved, illicitunknownantagonistDetails
DB01354HeptabarbitalexperimentalunknownantagonistDetails
DB01355HexobarbitalexperimentalunknownantagonistDetails
DB01483BarbitalillicitunknownantagonistDetails
DB01496Barbituric acid derivativeexperimental, illicitunknownantagonistDetails
DB00674Galantamineapprovedunknownallosteric modulatorDetails
DB00514DextromethorphanapprovedunknownantagonistDetails
DB09028CytisineexperimentalunknownagonistDetails
DB00898EthanolapprovedunknownDetails
DB00783Estradiolapproved, investigational, vet_approvedunknownDetails
DB00564Carbamazepineapproved, investigationalunknownDetails
DB01245DecamethoniumapprovedunknownDetails
DB00657Mecamylamineapproved, investigationalunknownDetails
DB00981Physostigmineapproved, investigationalunknownDetails
DB00572Atropineapproved, vet_approvedunknownDetails
DB00747Scopolamineapproved, investigationalunknownDetails
DB07720EpibatidineexperimentalunknownagonistDetails
DB13952Estradiol acetateapproved, investigational, vet_approvedunknownDetails
DB13953Estradiol benzoateapproved, investigational, vet_approvedunknownDetails
DB13954Estradiol cypionateapproved, investigational, vet_approvedunknownDetails
DB13955Estradiol dienanthateapproved, investigational, vet_approvedunknownDetails
DB13956Estradiol valerateapproved, investigational, vet_approvedunknownDetails
DB00915AmantadineapprovedunknownantagonistDetails
DB00753Isofluraneapproved, vet_approvedunknownantagonistDetails