Muscarinic acetylcholine receptor M2

Function

Muscarinic receptor for acetylcholine, a neurotransmitter found in the brain, neuromuscular junctions and the autonomic ganglia. Ligand binding causes a conformation change that triggers signaling via guanine nucleotide-binding proteins (G proteins) and modulates the activity of downstream effectors, such as adenylate cyclase. CHRM2 is coupled to G(i)/G(o) (GNAI1 or GNAO1) G proteins and mediates signaling by inhibiting adenylate cyclase activity.

Classification

Family (Pfam)

PF00001 7tm_1

InterPro

GPCR_Rhodpsn, GPCR_Rhodpsn_7TM, Musac_Ach_M2_rcpt, Musac_Ach_rcpt

Functional cluster

Membrane Transporters & GPCRs

Experimental structures · PDB · 17

• 3UON X-ray 3.00A
• 4MQS X-ray 3.50A
• 4MQT X-ray 3.70A
• 5YC8 X-ray 2.50A
• 5ZK3 X-ray 2.60A
• 5ZK8 X-ray 3.00A
• 5ZKB X-ray 2.95A
• 5ZKC X-ray 2.30A
• 6OIK EM 3.60A
• 6U1N EM 4.00A
• 7T8X EM 3.21A
• 7T90 EM 3.32A
• … and 5 more

A predicted model is available from AlphaFold.

Gene Ontology · 23

• GO:0098981 cholinergic synapse
• GO:0030669 clathrin-coated endocytic vesicle membrane
• GO:0030425 dendrite
• GO:0016020 membrane
• GO:0005886 plasma membrane
• GO:0045211 postsynaptic membrane
• GO:0098793 presynapse
• GO:0045202 synapse
• GO:1990763 arrestin family protein binding
• GO:0016907 G protein-coupled acetylcholine receptor activity
• GO:0007197 adenylate cyclase-inhibiting G protein-coupled acetylcholine receptor signaling pathway
• GO:0007193 adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway
• GO:0007188 adenylate cyclase-modulating G protein-coupled receptor signaling pathway
• GO:0007268 chemical synaptic transmission
• GO:0007213 G protein-coupled acetylcholine receptor signaling pathway
• GO:0007186 G protein-coupled receptor signaling pathway
• GO:0007187 G protein-coupled receptor signaling pathway, coupled to cyclic nucleotide second messenger
• GO:0007399 nervous system development
• GO:0007207 phospholipase C-activating G protein-coupled acetylcholine receptor signaling pathway
• GO:0099171 presynaptic modulation of chemical synaptic transmission
• GO:0008016 regulation of heart contraction
• GO:0006940 regulation of smooth muscle contraction
• GO:0009615 response to virus

Disease associations

• alcohol dependence MONDO:0007079
• major depressive disorder MONDO:0002009

Drugs targeting this protein · 19

• OXYBUTYNIN CHLORIDE antagonist
• SOLIFENACIN SUCCINATE antagonist
• DARIFENACIN HYDROBROMIDE antagonist
• FESOTERODINE FUMARATE antagonist
• OXYBUTYNIN antagonist
• PROPANTHELINE BROMIDE antagonist
• TOLTERODINE TARTRATE antagonist
• BETHANECHOL CHLORIDE agonist
• TALSACLIDINE partial agonist
• ATROPINE SULFATE antagonist
• DAROTROPIUM BROMIDE antagonist
• BATEFENTEROL antagonist
• TROSPIUM CHLORIDE antagonist
• ALCURONIUM positive allosteric modulator
• AFACIFENACIN antagonist
• SOFPIRONIUM BROMIDE inhibitor
• GLYCOPYRRONIUM TOSYLATE inhibitor
• ATROPINE antagonist
• TERODILINE HYDROCHLORIDE antagonist

Related proteins · sequence + function similarity

• Muscarinic acetylcholine receptor M2 0.99
• Muscarinic acetylcholine receptor M2 0.99
• Muscarinic acetylcholine receptor M2 0.97
• Muscarinic acetylcholine receptor M2 0.97
• Muscarinic acetylcholine receptor M2 0.97
• Muscarinic acetylcholine receptor M2 0.96
• Muscarinic acetylcholine receptor M4 0.92
• Muscarinic acetylcholine receptor M4 0.90
• Muscarinic acetylcholine receptor M4 0.86
• Muscarinic acetylcholine receptor M4 0.86
• Muscarinic acetylcholine receptor M4 0.86
• Muscarinic acetylcholine receptor M5 0.83

Co-cited proteins · studied together in the literature

• Muscarinic acetylcholine receptor M4 2 shared papers
• Muscarinic acetylcholine receptor M2 1 shared papers
• Small ribosomal subunit protein RACK1 1 shared papers
• Muscarinic acetylcholine receptor M4 1 shared papers
• Beta-arrestin-2 3 shared papers
• Muscarinic acetylcholine receptor M1 1 shared papers
• Muscarinic acetylcholine receptor M3 1 shared papers
• Muscarinic acetylcholine receptor M1 1 shared papers
• Beta-arrestin-1 1 shared papers
• Muscarinic acetylcholine receptor M3 1 shared papers
• Beta-2 adrenergic receptor 1 shared papers
• Beta-arrestin-1 2 shared papers

Literature · 13 cited papers

• Molecular insights into atypical modes of beta-arrestin interaction with seven transmembrane receptors. Science · 2024
• Structural snapshots uncover a key phosphorylation motif in GPCRs driving beta-arrestin activation. Mol. Cell · 2023
• Structural and dynamic insights into supra-physiological activation and allosteric modulation of a muscarinic acetylcholine receptor. Nat. Commun. · 2023
• Activation and allosteric modulation of a muscarinic acetylcholine receptor. Nature · 2013
• Structure of the human M2 muscarinic acetylcholine receptor bound to an antagonist. Nature · 2012
• RACK1 associates with muscarinic receptors and regulates M(2) receptor trafficking. PLoS ONE · 2010
• Transcriptomic and proteomic analyses of rhabdomyosarcoma cells reveal differential cellular gene expression in response to enterovirus 71 infection. Cell. Microbiol. · 2006
• The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. · 2004
• 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
• Human-specific amino acid changes found in 103 protein-coding genes. Mol. Biol. Evol. · 2004
• 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
• Distinct primary structures, ligand-binding properties and tissue-specific expression of four human muscarinic acetylcholine receptors. EMBO J. · 1987
• … and 1 more in the literature graph