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ACM2_HUMAN
ID   ACM2_HUMAN              Reviewed;         466 AA.
AC   P08172; Q4VBK6; Q9P1X9;
DT   01-AUG-1988, integrated into UniProtKB/Swiss-Prot.
DT   01-AUG-1988, sequence version 1.
DT   03-AUG-2022, entry version 212.
DE   RecName: Full=Muscarinic acetylcholine receptor M2;
GN   Name=CHRM2;
OS   Homo sapiens (Human).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC   Homo.
OX   NCBI_TaxID=9606;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX   PubMed=3037705; DOI=10.1126/science.3037705;
RA   Bonner T.I., Buckley N.J., Young A.C., Brann M.R.;
RT   "Identification of a family of muscarinic acetylcholine receptor genes.";
RL   Science 237:527-532(1987).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA], FUNCTION, AND SUBCELLULAR LOCATION.
RX   PubMed=3443095; DOI=10.1002/j.1460-2075.1987.tb02733.x;
RA   Peralta E.G., Ashkenazi A., Winslow J.W., Smith D.H., Ramachandran J.,
RA   Capon D.J.;
RT   "Distinct primary structures, ligand-binding properties and tissue-specific
RT   expression of four human muscarinic acetylcholine receptors.";
RL   EMBO J. 6:3923-3929(1987).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   TISSUE=Brain;
RA   Puhl H.L. III, Ikeda S.R., Aronstam R.S.;
RT   "cDNA clones of human proteins involved in signal transduction sequenced by
RT   the Guthrie cDNA resource center (www.cdna.org).";
RL   Submitted (APR-2002) to the EMBL/GenBank/DDBJ databases.
RN   [4]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RX   PubMed=15489334; DOI=10.1101/gr.2596504;
RG   The MGC Project Team;
RT   "The status, quality, and expansion of the NIH full-length cDNA project:
RT   the Mammalian Gene Collection (MGC).";
RL   Genome Res. 14:2121-2127(2004).
RN   [5]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 27-466.
RX   PubMed=15014171; DOI=10.1093/molbev/msh100;
RA   Kitano T., Liu Y.-H., Ueda S., Saitou N.;
RT   "Human-specific amino acid changes found in 103 protein-coding genes.";
RL   Mol. Biol. Evol. 21:936-944(2004).
RN   [6]
RP   INTERACTION WITH ARRB1 AND ARRB2.
RX   PubMed=7822302; DOI=10.1074/jbc.270.2.720;
RA   Gurevich V.V., Dion S.B., Onorato J.J., Ptasienski J., Kim C.M.,
RA   Sterne-Marr R., Hosey M.M., Benovic J.L.;
RT   "Arrestin interactions with G protein-coupled receptors. Direct binding
RT   studies of wild type and mutant arrestins with rhodopsin, beta 2-
RT   adrenergic, and m2 muscarinic cholinergic receptors.";
RL   J. Biol. Chem. 270:720-731(1995).
RN   [7]
RP   INDUCTION, AND IDENTIFICATION BY MASS SPECTROMETRY.
RX   PubMed=16548883; DOI=10.1111/j.1462-5822.2005.00644.x;
RA   Leong W.F., Chow V.T.;
RT   "Transcriptomic and proteomic analyses of rhabdomyosarcoma cells reveal
RT   differential cellular gene expression in response to enterovirus 71
RT   infection.";
RL   Cell. Microbiol. 8:565-580(2006).
RN   [8]
RP   INVOLVEMENT IN SUSCEPTIBILITY TO ALCOHOLISM AND MAJOR DEPRESSIVE DISORDER.
RX   PubMed=15229186; DOI=10.1093/hmg/ddh194;
RA   Wang J.C., Hinrichs A.L., Stock H., Budde J., Allen R., Bertelsen S.,
RA   Kwon J.M., Wu W., Dick D.M., Rice J., Jones K., Nurnberger J.I. Jr.,
RA   Tischfield J., Porjesz B., Edenberg H.J., Hesselbrock V., Crowe R.,
RA   Schuckit M., Begleiter H., Reich T., Goate A.M., Bierut L.J.;
RT   "Evidence of common and specific genetic effects: association of the
RT   muscarinic acetylcholine receptor M2 (CHRM2) gene with alcohol dependence
RT   and major depressive syndrome.";
RL   Hum. Mol. Genet. 13:1903-1911(2004).
RN   [9]
RP   INTERACTION WITH RACK1.
RX   PubMed=20976005; DOI=10.1371/journal.pone.0013517;
RA   Reiner C.L., McCullar J.S., Kow R.L., Le J.H., Goodlett D.R.,
RA   Nathanson N.M.;
RT   "RACK1 associates with muscarinic receptors and regulates M(2) receptor
RT   trafficking.";
RL   PLoS ONE 5:E13517-E13517(2010).
RN   [10]
RP   X-RAY CRYSTALLOGRAPHY (3.00 ANGSTROMS) IN COMPLEX WITH THE ANTAGONIST
RP   3-QUINUCLIDINYLBENZILATE, SUBCELLULAR LOCATION, TOPOLOGY, AND DISULFIDE
RP   BOND.
RX   PubMed=22278061; DOI=10.1038/nature10753;
RA   Haga K., Kruse A.C., Asada H., Yurugi-Kobayashi T., Shiroishi M., Zhang C.,
RA   Weis W.I., Okada T., Kobilka B.K., Haga T., Kobayashi T.;
RT   "Structure of the human M2 muscarinic acetylcholine receptor bound to an
RT   antagonist.";
RL   Nature 482:547-551(2012).
RN   [11]
RP   X-RAY CRYSTALLOGRAPHY (3.50 ANGSTROMS) IN COMPLEXES WITH THE AGONIST
RP   IPEROXO AND THE ALLOSTERIC EFFECTOR LY2119620, FUNCTION, SUBCELLULAR
RP   LOCATION, TOPOLOGY, DISULFIDE BOND, MOTIF, AND MUTAGENESIS OF ASN-58;
RP   ASP-103; TYR-206 AND ASN-404.
RX   PubMed=24256733; DOI=10.1038/nature12735;
RA   Kruse A.C., Ring A.M., Manglik A., Hu J., Hu K., Eitel K., Hubner H.,
RA   Pardon E., Valant C., Sexton P.M., Christopoulos A., Felder C.C.,
RA   Gmeiner P., Steyaert J., Weis W.I., Garcia K.C., Wess J., Kobilka B.K.;
RT   "Activation and allosteric modulation of a muscarinic acetylcholine
RT   receptor.";
RL   Nature 504:101-106(2013).
CC   -!- FUNCTION: The muscarinic acetylcholine receptor mediates various
CC       cellular responses, including inhibition of adenylate cyclase,
CC       breakdown of phosphoinositides and modulation of potassium channels
CC       through the action of G proteins. Primary transducing effect is
CC       adenylate cyclase inhibition. Signaling promotes phospholipase C
CC       activity, leading to the release of inositol trisphosphate (IP3); this
CC       then triggers calcium ion release into the cytosol.
CC       {ECO:0000269|PubMed:24256733, ECO:0000269|PubMed:3443095}.
CC   -!- SUBUNIT: Interacts with ARRB1 and ARRB2. Interacts with RACK1; the
CC       interaction regulates CHRM2 internalization.
CC       {ECO:0000269|PubMed:20976005, ECO:0000269|PubMed:22278061,
CC       ECO:0000269|PubMed:7822302}.
CC   -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:22278061,
CC       ECO:0000269|PubMed:24256733, ECO:0000269|PubMed:3443095}; Multi-pass
CC       membrane protein {ECO:0000269|PubMed:22278061,
CC       ECO:0000269|PubMed:24256733}. Postsynaptic cell membrane {ECO:0000305};
CC       Multi-pass membrane protein {ECO:0000305}. Note=Phosphorylation in
CC       response to agonist binding promotes receptor internalization.
CC       {ECO:0000250|UniProtKB:P06199}.
CC   -!- INDUCTION: Up-regulated in response to enterovirus 71 (EV71) infection.
CC       {ECO:0000269|PubMed:16548883}.
CC   -!- PTM: Phosphorylated in response to agonist treatment. {ECO:0000250}.
CC   -!- POLYMORPHISM: Genetic variations in CHRM2 can influence susceptibility
CC       to alcoholism [MIM:103780]. {ECO:0000305|PubMed:15229186}.
CC   -!- DISEASE: Major depressive disorder (MDD) [MIM:608516]: A common
CC       psychiatric disorder. It is a complex trait characterized by one or
CC       more major depressive episodes without a history of manic, mixed, or
CC       hypomanic episodes. A major depressive episode is characterized by at
CC       least 2 weeks during which there is a new onset or clear worsening of
CC       either depressed mood or loss of interest or pleasure in nearly all
CC       activities. Four additional symptoms must also be present including
CC       changes in appetite, weight, sleep, and psychomotor activity; decreased
CC       energy; feelings of worthlessness or guilt; difficulty thinking,
CC       concentrating, or making decisions; or recurrent thoughts of death or
CC       suicidal ideation, plans, or attempts. The episode must be accompanied
CC       by distress or impairment in social, occupational, or other important
CC       areas of functioning. {ECO:0000269|PubMed:15229186}. Note=Disease
CC       susceptibility is associated with variants affecting the gene
CC       represented in this entry.
CC   -!- SIMILARITY: Belongs to the G-protein coupled receptor 1 family.
CC       Muscarinic acetylcholine receptor subfamily. CHRM2 sub-subfamily.
CC       {ECO:0000255|PROSITE-ProRule:PRU00521}.
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DR   EMBL; M16404; AAA51570.1; -; Genomic_DNA.
DR   EMBL; X15264; CAA33335.1; -; Genomic_DNA.
DR   EMBL; AF498916; AAM18939.1; -; mRNA.
DR   EMBL; BC095547; AAH95547.1; -; mRNA.
DR   EMBL; BC106741; AAI06742.1; -; mRNA.
DR   EMBL; BC106742; AAI06743.1; -; mRNA.
DR   EMBL; AB041391; BAA94476.1; -; Genomic_DNA.
DR   CCDS; CCDS5843.1; -.
DR   PIR; S10126; S10126.
DR   RefSeq; NP_000730.1; NM_000739.2.
DR   RefSeq; NP_001006627.1; NM_001006626.1.
DR   RefSeq; NP_001006628.1; NM_001006627.1.
DR   RefSeq; NP_001006629.1; NM_001006628.1.
DR   RefSeq; NP_001006630.1; NM_001006629.1.
DR   RefSeq; NP_001006631.1; NM_001006630.1.
DR   RefSeq; NP_001006632.1; NM_001006631.1.
DR   RefSeq; NP_001006633.1; NM_001006632.1.
DR   RefSeq; XP_011514071.1; XM_011515769.2.
DR   PDB; 3UON; X-ray; 3.00 A; A=1-217, A=377-466.
DR   PDB; 4MQS; X-ray; 3.50 A; A=1-466.
DR   PDB; 4MQT; X-ray; 3.70 A; A=1-466.
DR   PDB; 5YC8; X-ray; 2.50 A; A=10-466.
DR   PDB; 5ZK3; X-ray; 2.60 A; A=10-466.
DR   PDB; 5ZK8; X-ray; 3.00 A; A=10-466.
DR   PDB; 5ZKB; X-ray; 2.95 A; A=10-466.
DR   PDB; 5ZKC; X-ray; 2.30 A; A=10-466.
DR   PDB; 6OIK; EM; 3.60 A; R=3-466.
DR   PDB; 6U1N; EM; 4.00 A; R=2-466.
DR   PDBsum; 3UON; -.
DR   PDBsum; 4MQS; -.
DR   PDBsum; 4MQT; -.
DR   PDBsum; 5YC8; -.
DR   PDBsum; 5ZK3; -.
DR   PDBsum; 5ZK8; -.
DR   PDBsum; 5ZKB; -.
DR   PDBsum; 5ZKC; -.
DR   PDBsum; 6OIK; -.
DR   PDBsum; 6U1N; -.
DR   AlphaFoldDB; P08172; -.
DR   SMR; P08172; -.
DR   BioGRID; 107551; 19.
DR   DIP; DIP-56282N; -.
DR   IntAct; P08172; 23.
DR   MINT; P08172; -.
DR   STRING; 9606.ENSP00000399745; -.
DR   BindingDB; P08172; -.
DR   ChEMBL; CHEMBL211; -.
DR   DrugBank; DB03128; Acetylcholine.
DR   DrugBank; DB08897; Aclidinium.
DR   DrugBank; DB05752; ALKS 27.
DR   DrugBank; DB00321; Amitriptyline.
DR   DrugBank; DB00543; Amoxapine.
DR   DrugBank; DB00517; Anisotropine methylbromide.
DR   DrugBank; DB01238; Aripiprazole.
DR   DrugBank; DB14185; Aripiprazole lauroxil.
DR   DrugBank; DB00572; Atropine.
DR   DrugBank; DB00767; Benzquinamide.
DR   DrugBank; DB01019; Bethanechol.
DR   DrugBank; DB00835; Brompheniramine.
DR   DrugBank; DB09300; Butylscopolamine.
DR   DrugBank; DB00411; Carbamoylcholine.
DR   DrugBank; DB01239; Chlorprothixene.
DR   DrugBank; DB00568; Cinnarizine.
DR   DrugBank; DB00363; Clozapine.
DR   DrugBank; DB00907; Cocaine.
DR   DrugBank; DB00785; Cryptenamine.
DR   DrugBank; DB00434; Cyproheptadine.
DR   DrugBank; DB00496; Darifenacin.
DR   DrugBank; DB01151; Desipramine.
DR   DrugBank; DB00804; Dicyclomine.
DR   DrugBank; DB08801; Dimetindene.
DR   DrugBank; DB01075; Diphenhydramine.
DR   DrugBank; DB01231; Diphenidol.
DR   DrugBank; DB00280; Disopyramide.
DR   DrugBank; DB09167; Dosulepin.
DR   DrugBank; DB01135; Doxacurium.
DR   DrugBank; DB01142; Doxepin.
DR   DrugBank; DB00366; Doxylamine.
DR   DrugBank; DB09194; Etoperidone.
DR   DrugBank; DB06702; Fesoterodine.
DR   DrugBank; DB01148; Flavoxate.
DR   DrugBank; DB00483; Gallamine triethiodide.
DR   DrugBank; DB00986; Glycopyrronium.
DR   DrugBank; DB06787; Hexocyclium.
DR   DrugBank; DB11181; Homatropine.
DR   DrugBank; DB00725; Homatropine methylbromide.
DR   DrugBank; DB00424; Hyoscyamine.
DR   DrugBank; DB09262; Imidafenacin.
DR   DrugBank; DB00458; Imipramine.
DR   DrugBank; DB00332; Ipratropium.
DR   DrugBank; DB01221; Ketamine.
DR   DrugBank; DB00408; Loxapine.
DR   DrugBank; DB00934; Maprotiline.
DR   DrugBank; DB00454; Meperidine.
DR   DrugBank; DB06709; Methacholine.
DR   DrugBank; DB00940; Methantheline.
DR   DrugBank; DB01403; Methotrimeprazine.
DR   DrugBank; DB00462; Methscopolamine bromide.
DR   DrugBank; DB00340; Metixene.
DR   DrugBank; DB01336; Metocurine.
DR   DrugBank; DB01226; Mivacurium.
DR   DrugBank; DB00622; Nicardipine.
DR   DrugBank; DB00540; Nortriptyline.
DR   DrugBank; DB00334; Olanzapine.
DR   DrugBank; DB01062; Oxybutynin.
DR   DrugBank; DB00383; Oxyphencyclimine.
DR   DrugBank; DB01337; Pancuronium.
DR   DrugBank; DB00715; Paroxetine.
DR   DrugBank; DB01085; Pilocarpine.
DR   DrugBank; DB01338; Pipecuronium.
DR   DrugBank; DB06153; Pizotifen.
DR   DrugBank; DB00387; Procyclidine.
DR   DrugBank; DB00392; Profenamine.
DR   DrugBank; DB01069; Promethazine.
DR   DrugBank; DB00777; Propiomazine.
DR   DrugBank; DB12278; Propiverine.
DR   DrugBank; DB01224; Quetiapine.
DR   DrugBank; DB04834; Rapacuronium.
DR   DrugBank; DB11855; Revefenacin.
DR   DrugBank; DB13581; Rociverine.
DR   DrugBank; DB00728; Rocuronium.
DR   DrugBank; DB00747; Scopolamine.
DR   DrugBank; DB01591; Solifenacin.
DR   DrugBank; DB00202; Succinylcholine.
DR   DrugBank; DB00342; Terfenadine.
DR   DrugBank; DB11235; Thonzylamine.
DR   DrugBank; DB01409; Tiotropium.
DR   DrugBank; DB01036; Tolterodine.
DR   DrugBank; DB00505; Tridihexethyl.
DR   DrugBank; DB00508; Triflupromazine.
DR   DrugBank; DB00376; Trihexyphenidyl.
DR   DrugBank; DB09089; Trimebutine.
DR   DrugBank; DB00726; Trimipramine.
DR   DrugBank; DB00809; Tropicamide.
DR   DrugBank; DB09076; Umeclidinium.
DR   DrugBank; DB00246; Ziprasidone.
DR   DrugCentral; P08172; -.
DR   GuidetoPHARMACOLOGY; 14; -.
DR   GlyGen; P08172; 4 sites.
DR   iPTMnet; P08172; -.
DR   PhosphoSitePlus; P08172; -.
DR   SwissPalm; P08172; -.
DR   BioMuta; CHRM2; -.
DR   DMDM; 113122; -.
DR   MassIVE; P08172; -.
DR   PaxDb; P08172; -.
DR   PeptideAtlas; P08172; -.
DR   PRIDE; P08172; -.
DR   ProteomicsDB; 52076; -.
DR   ABCD; P08172; 3 sequenced antibodies.
DR   Antibodypedia; 18171; 566 antibodies from 39 providers.
DR   DNASU; 1129; -.
DR   Ensembl; ENST00000320658.9; ENSP00000319984.5; ENSG00000181072.12.
DR   Ensembl; ENST00000401861.1; ENSP00000384401.1; ENSG00000181072.12.
DR   Ensembl; ENST00000445907.6; ENSP00000399745.2; ENSG00000181072.12.
DR   Ensembl; ENST00000453373.5; ENSP00000415386.1; ENSG00000181072.12.
DR   Ensembl; ENST00000680005.1; ENSP00000505686.1; ENSG00000181072.12.
DR   GeneID; 1129; -.
DR   KEGG; hsa:1129; -.
DR   MANE-Select; ENST00000680005.1; ENSP00000505686.1; NM_001006630.2; NP_001006631.1.
DR   UCSC; uc003vtg.2; human.
DR   CTD; 1129; -.
DR   DisGeNET; 1129; -.
DR   GeneCards; CHRM2; -.
DR   HGNC; HGNC:1951; CHRM2.
DR   HPA; ENSG00000181072; Tissue enhanced (heart muscle, intestine).
DR   MIM; 103780; phenotype.
DR   MIM; 118493; gene.
DR   MIM; 608516; phenotype.
DR   neXtProt; NX_P08172; -.
DR   OpenTargets; ENSG00000181072; -.
DR   PharmGKB; PA111; -.
DR   VEuPathDB; HostDB:ENSG00000181072; -.
DR   eggNOG; KOG4220; Eukaryota.
DR   GeneTree; ENSGT00940000158940; -.
DR   HOGENOM; CLU_009579_11_2_1; -.
DR   InParanoid; P08172; -.
DR   OMA; TSERQNH; -.
DR   OrthoDB; 1025450at2759; -.
DR   PhylomeDB; P08172; -.
DR   TreeFam; TF320495; -.
DR   PathwayCommons; P08172; -.
DR   Reactome; R-HSA-390648; Muscarinic acetylcholine receptors.
DR   Reactome; R-HSA-418594; G alpha (i) signalling events.
DR   Reactome; R-HSA-8856825; Cargo recognition for clathrin-mediated endocytosis.
DR   Reactome; R-HSA-8856828; Clathrin-mediated endocytosis.
DR   SignaLink; P08172; -.
DR   SIGNOR; P08172; -.
DR   BioGRID-ORCS; 1129; 12 hits in 1067 CRISPR screens.
DR   ChiTaRS; CHRM2; human.
DR   GeneWiki; Muscarinic_acetylcholine_receptor_M2; -.
DR   GenomeRNAi; 1129; -.
DR   Pharos; P08172; Tclin.
DR   PRO; PR:P08172; -.
DR   Proteomes; UP000005640; Chromosome 7.
DR   RNAct; P08172; protein.
DR   Bgee; ENSG00000181072; Expressed in stromal cell of endometrium and 69 other tissues.
DR   ExpressionAtlas; P08172; baseline and differential.
DR   Genevisible; P08172; HS.
DR   GO; GO:0070161; C:anchoring junction; IEA:UniProtKB-KW.
DR   GO; GO:0032279; C:asymmetric synapse; IEA:Ensembl.
DR   GO; GO:0043679; C:axon terminus; IEA:Ensembl.
DR   GO; GO:0098981; C:cholinergic synapse; IEA:Ensembl.
DR   GO; GO:0030669; C:clathrin-coated endocytic vesicle membrane; TAS:Reactome.
DR   GO; GO:0030425; C:dendrite; IBA:GO_Central.
DR   GO; GO:0098978; C:glutamatergic synapse; IEA:Ensembl.
DR   GO; GO:0016021; C:integral component of membrane; IDA:CAFA.
DR   GO; GO:0005887; C:integral component of plasma membrane; IDA:UniProtKB.
DR   GO; GO:0099055; C:integral component of postsynaptic membrane; IEA:Ensembl.
DR   GO; GO:0099056; C:integral component of presynaptic membrane; IEA:Ensembl.
DR   GO; GO:0043025; C:neuronal cell body; IEA:Ensembl.
DR   GO; GO:0005886; C:plasma membrane; IDA:LIFEdb.
DR   GO; GO:0032280; C:symmetric synapse; IEA:Ensembl.
DR   GO; GO:0045202; C:synapse; IBA:GO_Central.
DR   GO; GO:1990763; F:arrestin family protein binding; IPI:CAFA.
DR   GO; GO:0016907; F:G protein-coupled acetylcholine receptor activity; IDA:UniProtKB.
DR   GO; GO:0004993; F:G protein-coupled serotonin receptor activity; IBA:GO_Central.
DR   GO; GO:0030594; F:neurotransmitter receptor activity; IBA:GO_Central.
DR   GO; GO:0007197; P:adenylate cyclase-inhibiting G protein-coupled acetylcholine receptor signaling pathway; IBA:GO_Central.
DR   GO; GO:0007188; P:adenylate cyclase-modulating G protein-coupled receptor signaling pathway; TAS:ProtInc.
DR   GO; GO:0007268; P:chemical synaptic transmission; IBA:GO_Central.
DR   GO; GO:0007213; P:G protein-coupled acetylcholine receptor signaling pathway; IDA:UniProtKB.
DR   GO; GO:0007186; P:G protein-coupled receptor signaling pathway; TAS:ProtInc.
DR   GO; GO:0007187; P:G protein-coupled receptor signaling pathway, coupled to cyclic nucleotide second messenger; IBA:GO_Central.
DR   GO; GO:0007399; P:nervous system development; TAS:ProtInc.
DR   GO; GO:0007207; P:phospholipase C-activating G protein-coupled acetylcholine receptor signaling pathway; TAS:ProtInc.
DR   GO; GO:0008016; P:regulation of heart contraction; TAS:ProtInc.
DR   GO; GO:0006940; P:regulation of smooth muscle contraction; IBA:GO_Central.
DR   GO; GO:2000300; P:regulation of synaptic vesicle exocytosis; IEA:Ensembl.
DR   GO; GO:0009615; P:response to virus; IEP:UniProtKB.
DR   InterPro; IPR000276; GPCR_Rhodpsn.
DR   InterPro; IPR017452; GPCR_Rhodpsn_7TM.
DR   InterPro; IPR001065; Musac_Ach_M2_rcpt.
DR   InterPro; IPR000995; Musac_Ach_rcpt.
DR   Pfam; PF00001; 7tm_1; 1.
DR   PRINTS; PR00237; GPCRRHODOPSN.
DR   PRINTS; PR00243; MUSCARINICR.
DR   PRINTS; PR00539; MUSCRINICM2R.
DR   SMART; SM01381; 7TM_GPCR_Srsx; 1.
DR   PROSITE; PS00237; G_PROTEIN_RECEP_F1_1; 1.
DR   PROSITE; PS50262; G_PROTEIN_RECEP_F1_2; 1.
PE   1: Evidence at protein level;
KW   3D-structure; Cell membrane; Disulfide bond; G-protein coupled receptor;
KW   Glycoprotein; Membrane; Phosphoprotein; Postsynaptic cell membrane;
KW   Receptor; Reference proteome; Synapse; Transducer; Transmembrane;
KW   Transmembrane helix.
FT   CHAIN           1..466
FT                   /note="Muscarinic acetylcholine receptor M2"
FT                   /id="PRO_0000069021"
FT   TOPO_DOM        1..22
FT                   /note="Extracellular"
FT   TRANSMEM        23..45
FT                   /note="Helical; Name=1"
FT   TOPO_DOM        46..59
FT                   /note="Cytoplasmic"
FT   TRANSMEM        60..80
FT                   /note="Helical; Name=2"
FT   TOPO_DOM        81..97
FT                   /note="Extracellular"
FT   TRANSMEM        98..119
FT                   /note="Helical; Name=3"
FT   TOPO_DOM        120..139
FT                   /note="Cytoplasmic"
FT   TRANSMEM        140..162
FT                   /note="Helical; Name=4"
FT   TOPO_DOM        163..184
FT                   /note="Extracellular"
FT   TRANSMEM        185..209
FT                   /note="Helical; Name=5"
FT   TOPO_DOM        210..387
FT                   /note="Cytoplasmic"
FT   TRANSMEM        388..410
FT                   /note="Helical; Name=6"
FT   TOPO_DOM        411..418
FT                   /note="Extracellular"
FT   TRANSMEM        419..442
FT                   /note="Helical; Name=7"
FT   TOPO_DOM        443..466
FT                   /note="Cytoplasmic"
FT   REGION          218..355
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   MOTIF           120..122
FT                   /note="Important for signaling"
FT   MOTIF           436..440
FT                   /note="Important for signaling"
FT   COMPBIAS        230..256
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        280..297
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        305..355
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   MOD_RES         232
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:Q9ERZ4"
FT   MOD_RES         446
FT                   /note="Phosphothreonine"
FT                   /evidence="ECO:0000255"
FT   MOD_RES         450
FT                   /note="Phosphothreonine"
FT                   /evidence="ECO:0000255"
FT   MOD_RES         465
FT                   /note="Phosphothreonine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        2
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        3
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        6
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        9
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   DISULFID        96..176
FT   DISULFID        413..416
FT   MUTAGEN         58
FT                   /note="N->A: Nearly abolishes signaling via downstream
FT                   effectors."
FT                   /evidence="ECO:0000269|PubMed:24256733"
FT   MUTAGEN         103
FT                   /note="D->E: Reduced affinity for acetylcholine. Abolishes
FT                   signaling via downstream effectors."
FT                   /evidence="ECO:0000269|PubMed:24256733"
FT   MUTAGEN         206
FT                   /note="Y->F: Abolishes signaling via downstream effectors."
FT                   /evidence="ECO:0000269|PubMed:24256733"
FT   MUTAGEN         404
FT                   /note="N->Q: Reduced affinity for acetylcholine. Reduces
FT                   signaling via downstream effectors."
FT                   /evidence="ECO:0000269|PubMed:24256733"
FT   HELIX           17..50
FT                   /evidence="ECO:0007829|PDB:5ZKC"
FT   HELIX           52..54
FT                   /evidence="ECO:0007829|PDB:5ZKC"
FT   HELIX           57..74
FT                   /evidence="ECO:0007829|PDB:5ZKC"
FT   HELIX           76..86
FT                   /evidence="ECO:0007829|PDB:5ZKC"
FT   HELIX           93..126
FT                   /evidence="ECO:0007829|PDB:5ZKC"
FT   TURN            128..131
FT                   /evidence="ECO:0007829|PDB:5ZKC"
FT   HELIX           132..134
FT                   /evidence="ECO:0007829|PDB:5ZKC"
FT   HELIX           137..166
FT                   /evidence="ECO:0007829|PDB:5ZKC"
FT   HELIX           179..182
FT                   /evidence="ECO:0007829|PDB:5ZKC"
FT   HELIX           184..194
FT                   /evidence="ECO:0007829|PDB:5ZKC"
FT   HELIX           196..213
FT                   /evidence="ECO:0007829|PDB:5ZKC"
FT   HELIX           382..410
FT                   /evidence="ECO:0007829|PDB:5ZKC"
FT   HELIX           414..416
FT                   /evidence="ECO:0007829|PDB:5YC8"
FT   HELIX           419..440
FT                   /evidence="ECO:0007829|PDB:5ZKC"
FT   HELIX           441..443
FT                   /evidence="ECO:0007829|PDB:5ZKC"
FT   HELIX           445..455
FT                   /evidence="ECO:0007829|PDB:5ZKC"
SQ   SEQUENCE   466 AA;  51715 MW;  2FC2FD7748C22BEC CRC64;
     MNNSTNSSNN SLALTSPYKT FEVVFIVLVA GSLSLVTIIG NILVMVSIKV NRHLQTVNNY
     FLFSLACADL IIGVFSMNLY TLYTVIGYWP LGPVVCDLWL ALDYVVSNAS VMNLLIISFD
     RYFCVTKPLT YPVKRTTKMA GMMIAAAWVL SFILWAPAIL FWQFIVGVRT VEDGECYIQF
     FSNAAVTFGT AIAAFYLPVI IMTVLYWHIS RASKSRIKKD KKEPVANQDP VSPSLVQGRI
     VKPNNNNMPS SDDGLEHNKI QNGKAPRDPV TENCVQGEEK ESSNDSTSVS AVASNMRDDE
     ITQDENTVST SLGHSKDENS KQTCIRIGTK TPKSDSCTPT NTTVEVVGSS GQNGDEKQNI
     VARKIVKMTK QPAKKKPPPS REKKVTRTIL AILLAFIITW APYNVMVLIN TFCAPCIPNT
     VWTIGYWLCY INSTINPACY ALCNATFKKT FKHLLMCHYK NIGATR
 
 
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