Muscarinic acetylcholine receptor M2

Details

Name
Muscarinic acetylcholine receptor M2
Kind
protein
Synonyms
Not Available
Gene Name
CHRM2
UniProtKB Entry
P08172Swiss-Prot
Organism
Humans
NCBI Taxonomy ID
9606
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
arrestin family protein binding / G protein-coupled acetylcholine receptor activity / G protein-coupled serotonin receptor activity
Processes
adenylate cyclase-inhibiting G protein-coupled acetylcholine receptor signaling pathway / adenylate cyclase-modulating G protein-coupled receptor signaling pathway / chemical synaptic transmission / 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 / phospholipase C-activating G protein-coupled acetylcholine receptor signaling pathway / presynaptic modulation of chemical synaptic transmission
Components
cholinergic synapse / clathrin-coated endocytic vesicle membrane / glutamatergic synapse / membrane / presynaptic membrane
General 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
Specific Function
arrestin family protein binding
Pfam Domain Function
Signal Regions
Not Available
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
7q33
External Identifiers
ResourceLink
UniProtKB IDP08172
UniProtKB Entry NameACM2_HUMAN
GenBank Protein ID177990
GenBank Gene IDM16404
GeneCard IDCHRM2
GenAtlas IDCHRM2
HGNC IDHGNC:1951
PDB ID(s)3UON, 4MQS, 4MQT, 5YC8, 5ZK3, 5ZK8, 5ZKB, 5ZKC, 6OIK, 6U1N, 7T8X, 7T90, 7T94, 7T96, 8J8R, 8J97, 8JAF
KEGG IDhsa:1129
IUPHAR/Guide To Pharmacology ID14
NCBI Gene ID1129
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. [Article]
  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. [Article]
  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. [Article]
  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. [Article]
  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. [Article]
  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. [Article]
  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. [Article]
  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. [Article]
  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. [Article]
  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. [Article]

Associated Data

Drug Relations
DrugDrug groupPharmacological action?TypeActionsDetails
Atropineapproved, vet_approvedyestargetantagonistDetails
Homatropine methylbromideapprovedyestargetantagonistDetails
CryptenamineapprovedyestargetantagonistDetails
Diphenidolapproved, investigational, withdrawnyestargetantagonistDetails
Ipratropiumapproved, experimentalyestargetantagonistDetails
Olanzapineapproved, investigationalunknowntargetantagonistDetails
OxyphencyclimineapprovedyestargetantagonistDetails
ProcyclidineapprovedyestargetantagonistDetails
CarbamoylcholineapprovedyestargetagonistDetails
HyoscyamineapprovedyestargetantagonistDetails
Gallamine triethiodideapprovedyestargetantagonistDetails
TridihexethylwithdrawnyestargetantagonistDetails
Triflupromazineapproved, vet_approvedyestargetantagonistDetails
Anisotropine methylbromideapprovedyestargetantagonistDetails
RocuroniumapprovedyestargetantagonistDetails
BenzquinamidewithdrawnyestargetantagonistDetails
Tolterodineapproved, investigationalyestargetantagonistDetails
Promethazineapproved, investigationalunknowntargetantagonistDetails
DoxacuriumapprovedunknowntargetantagonistDetails
FlavoxateapprovedyestargetantagonistDetails
Desipramineapproved, investigationalnotargetantagonistDetails
Mivacuriumapprovednotargetantagonistpartial agonistDetails
Methotrimeprazineapproved, investigationalunknowntargetantagonistDetails
Oxybutyninapproved, investigationalyestargetantagonistDetails
Pilocarpineapproved, investigationalyestargetagonistDetails
MetocurineapprovedunknowntargetantagonistDetails
ALKS 27investigationalunknowntargetDetails
Nicardipineapproved, investigationalunknowntargetantagonistDetails
QuetiapineapprovedunknowntargetligandDetails
TiotropiumapprovedunknowntargetantagonistDetails
ZiprasidoneapprovedunknowntargetantagonistDetails
Clozapineapprovedunknowntargetpartial agonistDetails
Darifenacinapproved, investigationalunknowntargetantagonistDetails
Cocaineapproved, illicitunknowntargetantagonistDetails
PipecuroniumapprovedunknowntargetantagonistDetails
PancuroniumapprovedunknowntargetantagonistDetails
DisopyramideapprovedunknowntargetantagonistDetails
ProfenamineapprovedunknowntargetantagonistDetails
Chlorprothixeneapproved, experimental, investigational, withdrawnnotargetantagonistDetails
Doxepinapproved, investigationalunknowntargetantagonistDetails
ImipramineapprovednotargetantagonistDetails
CyproheptadineapprovedunknowntargetantagonistDetails
BrompheniramineapprovedunknowntargetantagonistDetails
Tropicamideapproved, investigationalyestargetantagonistDetails
DicyclomineapprovedunknowntargetantagonistDetails
Scopolamineapproved, investigationalyestargetantagonistDetails
TrihexyphenidylapprovedunknowntargetantagonistDetails
SolifenacinapprovedunknowntargetantagonistDetails
SuccinylcholineapprovedunknowntargetagonistDetails
Maprotilineapproved, investigationalnotargetantagonistDetails
Methscopolamine bromideapprovedyestargetantagonistDetails
Dimetindeneapproved, investigationalyestargetantagonistDetails
FesoterodineapprovedunknowntargetantagonistDetails
BethanecholapprovedunknowntargetagonistDetails
AclidiniumapprovedyestargetantagonistDetails
LoxapineapprovedunknowntargetbinderDetails
Terfenadineapproved, withdrawnunknowntargetbinderDetails
Glycopyrroniumapproved, investigational, vet_approvedyestargetantagonistDetails
UmeclidiniumapprovedunknowntargetantagonistDetails
Diphenhydramineapproved, investigationalunknowntargetantagonistDetails
HexocycliumapprovedunknowntargetantagonistDetails
Butylscopolamineapproved, investigational, vet_approvedunknowntargetantagonistDetails
DosulepinapprovedyestargetantagonistDetails
ImidafenacininvestigationalyestargetantagonistDetails
Acetylcholineapproved, investigationalunknowntargetDetails
HomatropineapprovedyestargetantagonistDetails
PizotifenapprovedunknowntargetantagonistDetails
Propiverineapproved, investigationalyestargetantagonistDetails
ThonzylamineapprovedunknowntargetantagonistDetails
Rapacuroniumapproved, withdrawnyestargetantagonistDetails
RociverineexperimentalyestargetantagonistDetails
TrimebutineapprovedyestargetantagonistDetails
Aripiprazole lauroxilapproved, investigationalnotargetDetails
Aripiprazoleapproved, investigationalunknowntargetligandDetails
Methanthelineapproved, investigationalunknowntargetDetails
Methacholineapproved, investigationalyestargetagonistDetails
Viloxazineapproved, investigational, withdrawnunknowntargetantagonistDetails
Cisatracuriumapproved, investigationalunknowntargetantagonistDetails
Caramiphenexperimental, vet_approvedyestargetinhibitorDetails
MethscopolamineapprovedyestargetantagonistDetails
AceclidineapprovedyestargetinhibitorDetails