Muscarinic acetylcholine receptor M2

Details

Name
Muscarinic acetylcholine receptor M2
Synonyms
Not Available
Gene Name
CHRM2
Organism
Humans
Amino acid sequence
>lcl|BSEQ0016133|Muscarinic acetylcholine receptor M2
MNNSTNSSNNSLALTSPYKTFEVVFIVLVAGSLSLVTIIGNILVMVSIKVNRHLQTVNNY
FLFSLACADLIIGVFSMNLYTLYTVIGYWPLGPVVCDLWLALDYVVSNASVMNLLIISFD
RYFCVTKPLTYPVKRTTKMAGMMIAAAWVLSFILWAPAILFWQFIVGVRTVEDGECYIQF
FSNAAVTFGTAIAAFYLPVIIMTVLYWHISRASKSRIKKDKKEPVANQDPVSPSLVQGRI
VKPNNNNMPSSDDGLEHNKIQNGKAPRDPVTENCVQGEEKESSNDSTSVSAVASNMRDDE
ITQDENTVSTSLGHSKDENSKQTCIRIGTKTPKSDSCTPTNTTVEVVGSSGQNGDEKQNI
VARKIVKMTKQPAKKKPPPSREKKVTRTILAILLAFIITWAPYNVMVLINTFCAPCIPNT
VWTIGYWLCYINSTINPACYALCNATFKKTFKHLLMCHYKNIGATR
Number of residues
466
Molecular Weight
51714.605
Theoretical pI
9.08
GO Classification
Functions
drug binding / G-protein coupled acetylcholine receptor activity
Processes
adenylate cyclase-inhibiting G-protein coupled acetylcholine receptor signaling pathway / adenylate cyclase-modulating G-protein coupled receptor signaling pathway / G-protein coupled acetylcholine receptor signaling pathway / G-protein coupled receptor signaling pathway / G-protein coupled receptor signaling pathway, coupled to cyclic nucleotide second messenger / nervous system development / phospholipase C-activating G-protein coupled acetylcholine receptor signaling pathway / regulation of heart contraction / regulation of smooth muscle contraction / response to virus / sensory perception of chemical stimulus / synaptic transmission, cholinergic
Components
asymmetric synapse / axon terminus / cell junction / dendrite / integral component of plasma membrane / neuronal cell body / plasma membrane / postsynaptic membrane / symmetric synapse / synapse
General Function
G-protein coupled acetylcholine receptor activity
Specific Function
The muscarinic acetylcholine receptor mediates various cellular responses, including inhibition of adenylate cyclase, breakdown of phosphoinositides and modulation of potassium channels through the action of G proteins. Primary transducing effect is adenylate cyclase inhibition. Signaling promotes phospholipase C activity, leading to the release of inositol trisphosphate (IP3); this then triggers calcium ion release into the cytosol.
Pfam Domain Function
Transmembrane Regions
23-45 60-80 98-119 140-162 185-209 388-410 419-442
Cellular Location
Cell membrane
Gene sequence
>lcl|BSEQ0016134|Muscarinic acetylcholine receptor M2 (CHRM2)
ATGAATAACTCAACAAACTCCTCTAACAATAGCCTGGCTCTTACAAGTCCTTATAAGACA
TTTGAAGTGGTGTTTATTGTCCTGGTGGCTGGATCCCTCAGTTTGGTGACCATTATCGGG
AACATCCTAGTCATGGTTTCCATTAAAGTCAACCGCCACCTCCAGACCGTCAACAATTAC
TTTTTATTCAGCTTGGCCTGTGCTGACCTTATCATAGGTGTTTTCTCCATGAACTTGTAC
ACCCTCTACACTGTGATTGGTTACTGGCCTTTGGGACCTGTGGTGTGTGACCTTTGGCTA
GCCCTGGACTATGTGGTCAGCAATGCCTCAGTTATGAATCTGCTCATCATCAGCTTTGAC
AGGTACTTCTGTGTCACAAAACCTCTGACCTACCCAGTCAAGCGGACCACAAAAATGGCA
GGTATGATGATTGCAGCTGCCTGGGTCCTCTCTTTCATCCTCTGGGCTCCAGCCATTCTC
TTCTGGCAGTTCATTGTAGGGGTGAGAACTGTGGAGGATGGGGAGTGCTACATTCAGTTT
TTTTCCAATGCTGCTGTCACCTTTGGTACGGCTATTGCAGCCTTCTATTTGCCAGTGATC
ATCATGACTGTGCTATATTGGCACATATCCCGAGCCAGCAAGAGCAGGATAAAGAAGGAC
AAGAAGGAGCCTGTTGCCAACCAAGACCCCGTTTCTCCAAGTCTGGTACAAGGAAGGATA
GTGAAGCCAAACAATAACAACATGCCCAGCAGTGACGATGGCCTGGAGCACAACAAAATC
CAGAATGGCAAAGCCCCCAGGGATCCTGTGACTGAAAACTGTGTTCAGGGAGAGGAGAAG
GAGAGCTCCAATGACTCCACCTCAGTCAGTGCTGTTGCCTCTAATATGAGAGATGATGAA
ATAACCCAGGATGAAAACACAGTTTCCACTTCCCTGGGCCATTCCAAAGATGAGAACTCT
AAGCAAACATGCATCAGAATTGGCACCAAGACCCCAAAAAGTGACTCATGTACCCCAACT
AATACCACCGTGGAGGTAGTGGGGTCTTCAGGTCAGAATGGAGATGAAAAGCAGAATATT
GTAGCCCGCAAGATTGTGAAGATGACTAAGCAGCCTGCAAAAAAGAAGCCTCCTCCTTCC
CGGGAAAAGAAAGTCACCAGGACAATCTTGGCTATTCTGTTGGCTTTCATCATCACTTGG
GCCCCATACAATGTCATGGTGCTCATTAACACCTTTTGTGCACCTTGCATCCCCAACACT
GTGTGGACAATTGGTTACTGGCTTTGTTACATCAACAGCACTATCAACCCTGCCTGCTAT
GCACTTTGCAATGCCACCTTCAAGAAGACCTTTAAACACCTTCTCATGTGTCATTATAAG
AACATAGGCGCTACAAGGTAA
Chromosome Location
7
Locus
7q31-q35
External Identifiers
ResourceLink
UniProtKB IDP08172
UniProtKB Entry NameACM2_HUMAN
GenBank Protein ID177990
GenBank Gene IDM16404
GenAtlas IDCHRM2
HGNC IDHGNC:1951
General References
  1. Bonner TI, Buckley NJ, Young AC, Brann MR: Identification of a family of muscarinic acetylcholine receptor genes. Science. 1987 Jul 31;237(4814):527-32. [PubMed:3037705]
  2. Peralta EG, Ashkenazi A, Winslow JW, Smith DH, Ramachandran J, Capon DJ: Distinct primary structures, ligand-binding properties and tissue-specific expression of four human muscarinic acetylcholine receptors. EMBO J. 1987 Dec 20;6(13):3923-9. [PubMed:3443095]
  3. 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]
  4. Kitano T, Liu YH, Ueda S, Saitou N: Human-specific amino acid changes found in 103 protein-coding genes. Mol Biol Evol. 2004 May;21(5):936-44. Epub 2004 Mar 10. [PubMed:15014171]
  5. Gurevich VV, Dion SB, Onorato JJ, Ptasienski J, Kim CM, Sterne-Marr R, Hosey MM, Benovic JL: Arrestin interactions with G protein-coupled receptors. Direct binding studies of wild type and mutant arrestins with rhodopsin, beta 2-adrenergic, and m2 muscarinic cholinergic receptors. J Biol Chem. 1995 Jan 13;270(2):720-31. [PubMed:7822302]
  6. Leong WF, Chow VT: Transcriptomic and proteomic analyses of rhabdomyosarcoma cells reveal differential cellular gene expression in response to enterovirus 71 infection. Cell Microbiol. 2006 Apr;8(4):565-80. [PubMed:16548883]
  7. Wang JC, Hinrichs AL, Stock H, Budde J, Allen R, Bertelsen S, Kwon JM, Wu W, Dick DM, Rice J, Jones K, Nurnberger JI Jr, Tischfield J, Porjesz B, Edenberg HJ, Hesselbrock V, Crowe R, Schuckit M, Begleiter H, Reich T, Goate AM, Bierut LJ: Evidence of common and specific genetic effects: association of the muscarinic acetylcholine receptor M2 (CHRM2) gene with alcohol dependence and major depressive syndrome. Hum Mol Genet. 2004 Sep 1;13(17):1903-11. Epub 2004 Jun 30. [PubMed:15229186]
  8. Reiner CL, McCullar JS, Kow RL, Le JH, Goodlett DR, Nathanson NM: RACK1 associates with muscarinic receptors and regulates M(2) receptor trafficking. PLoS One. 2010 Oct 20;5(10):e13517. doi: 10.1371/journal.pone.0013517. [PubMed:20976005]
  9. Haga K, Kruse AC, Asada H, Yurugi-Kobayashi T, Shiroishi M, Zhang C, Weis WI, Okada T, Kobilka BK, Haga T, Kobayashi T: Structure of the human M2 muscarinic acetylcholine receptor bound to an antagonist. Nature. 2012 Jan 25;482(7386):547-51. doi: 10.1038/nature10753. [PubMed:22278061]
  10. Kruse AC, Ring AM, Manglik A, Hu J, Hu K, Eitel K, Hubner H, Pardon E, Valant C, Sexton PM, Christopoulos A, Felder CC, Gmeiner P, Steyaert J, Weis WI, Garcia KC, Wess J, Kobilka BK: Activation and allosteric modulation of a muscarinic acetylcholine receptor. Nature. 2013 Dec 5;504(7478):101-6. doi: 10.1038/nature12735. Epub 2013 Nov 20. [PubMed:24256733]

Drug Relations

Drug Relations
DrugBank IDNameDrug groupPharmacological action?ActionsDetails
DB00340MetixeneapprovedunknownantagonistDetails
DB00572Atropineapproved, vet_approvedyesantagonistDetails
DB00725Homatropine methylbromideapprovedyesantagonistDetails
DB00785CryptenamineapprovedyesantagonistDetails
DB01231Diphenidolapproved, investigational, withdrawnyesantagonistDetails
DB00332Ipratropiumapproved, experimentalyesantagonistDetails
DB00334Olanzapineapproved, investigationalunknownantagonistDetails
DB00383OxyphencyclimineapprovedyesantagonistDetails
DB00387ProcyclidineapprovedyesantagonistDetails
DB00411CarbamoylcholineapprovedyesagonistDetails
DB00420Promazineapproved, vet_approvedunknownantagonistDetails
DB00424HyoscyamineapprovedyesantagonistDetails
DB00483Gallamine triethiodideapprovedyesantagonistDetails
DB00505TridihexethylwithdrawnyesantagonistDetails
DB00508Triflupromazineapproved, vet_approvedyesantagonistDetails
DB00517Anisotropine methylbromideapprovedyesantagonistDetails
DB00728RocuroniumapprovedyesantagonistDetails
DB00767BenzquinamidewithdrawnyesantagonistDetails
DB00777PropiomazineapprovedunknownantagonistDetails
DB01036Tolterodineapproved, investigationalyesantagonistDetails
DB01069Promethazineapproved, investigationalunknownantagonistDetails
DB01135DoxacuriumapprovedunknownantagonistDetails
DB01148FlavoxateapprovedyesantagonistDetails
DB01151Desipramineapproved, investigationalnoantagonistDetails
DB01226Mivacuriumapprovednoantagonistpartial agonistDetails
DB01403Methotrimeprazineapproved, investigationalunknownantagonistDetails
DB01062Oxybutyninapproved, investigationalyesantagonistDetails
DB01085Pilocarpineapproved, investigationalyesagonistDetails
DB01336MetocurineapprovedunknownantagonistDetails
DB05752ALKS 27investigationalunknownDetails
DB00622Nicardipineapproved, investigationalunknownantagonistDetails
DB01224QuetiapineapprovedunknownligandDetails
DB01409TiotropiumapprovedunknownantagonistDetails
DB00246ZiprasidoneapprovednoantagonistDetails
DB00363ClozapineapprovednoantagonistDetails
DB00496Darifenacinapproved, investigationalunknownantagonistDetails
DB00907Cocaineapproved, illicitunknownantagonistDetails
DB01338PipecuroniumapprovedunknownantagonistDetails
DB01337PancuroniumapprovedunknownantagonistDetails
DB00280DisopyramideapprovedunknownantagonistDetails
DB00392ProfenamineapprovedunknownantagonistDetails
DB01239Chlorprothixeneapproved, experimental, investigational, withdrawnnoantagonistDetails
DB01142Doxepinapproved, investigationalunknownantagonistDetails
DB00458ImipramineapprovednoantagonistDetails
DB00540NortriptylineapprovednoantagonistDetails
DB00434CyproheptadineapprovedunknownantagonistDetails
DB00835BrompheniramineapprovedunknownantagonistDetails
DB00809Tropicamideapproved, investigationalunknownantagonistDetails
DB00804DicyclomineapprovedunknownantagonistDetails
DB00747Scopolamineapproved, investigationalunknownantagonistDetails
DB00376TrihexyphenidylapprovedunknownantagonistDetails
DB01591SolifenacinapprovedunknownantagonistDetails
DB00202SuccinylcholineapprovedunknownagonistDetails
DB00934Maprotilineapproved, investigationalnoantagonistDetails
DB00462Methscopolamine bromideapprovedyesantagonistDetails
DB08801Dimetindeneapproved, investigationalyesantagonistDetails
DB06702FesoterodineapprovedunknownantagonistDetails
DB01019BethanecholapprovedyesagonistDetails
DB08897AclidiniumapprovedyesantagonistDetails
DB00408LoxapineapprovedunknownbinderDetails
DB00342Terfenadineapproved, withdrawnunknownbinderDetails
DB00986Glycopyrroniumapproved, investigational, vet_approvedunknownbinderDetails
DB09076UmeclidiniumapprovedyesantagonistDetails
DB01075Diphenhydramineapproved, investigationalunknownantagonistDetails
DB06787HexocycliumapprovedunknownantagonistDetails
DB09300Butylscopolamineapproved, investigational, vet_approvedunknownantagonistDetails
DB09167DosulepinapprovedyesantagonistDetails
DB09262ImidafenacininvestigationalyesantagonistDetails
DB03128Acetylcholineapproved, investigationalunknownDetails
DB11181HomatropineapprovedyesantagonistDetails
DB06153PizotifenapprovedunknownantagonistDetails
DB12278Propiverineapproved, investigationalyesantagonistDetails
DB11235ThonzylamineapprovedunknownantagonistDetails
DB04834Rapacuroniumapproved, withdrawnyesantagonistDetails
DB13581RociverineexperimentalyesantagonistDetails
DB09089TrimebutineapprovedyesantagonistDetails
DB14185Aripiprazole lauroxilapproved, investigationalnoDetails
DB01238Aripiprazoleapproved, investigationalunknownligandDetails
DB00543AmoxapineapprovedunknownantagonistDetails
DB00726TrimipramineapprovedunknownbinderDetails
DB00454MeperidineapprovedunknownbinderDetails
DB00568Cinnarizineapproved, investigationalunknownbinderDetails
DB01221Ketamineapproved, vet_approvedunknownbinderDetails
DB09194EtoperidonewithdrawnunknownantagonistDetails
DB00555Lamotrigineapproved, investigationalunknowninhibitorDetails
DB11855Revefenacinapproved, investigationalyesantagonistDetails
DB00321AmitriptylineapprovedunknownligandDetails
DB00715Paroxetineapproved, investigationalunknowninhibitorDetails