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P08172 (ACM2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 152. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (5) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Muscarinic acetylcholine receptor M2
Gene names
Name:CHRM2
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length466 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

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.

Subunit structure

Interacts with ARRB1 and ARRB2. Interacts with GNB2L1/RACK1; the interaction regulates CHRM2 internalization. Ref.6 Ref.9

Subcellular location

Cell membrane; Multi-pass membrane protein. Cell junctionsynapsepostsynaptic cell membrane; Multi-pass membrane protein.

Induction

Up-regulated in response to enterovirus 71 (EV71) infection. Ref.7

Polymorphism

Genetic variations in CHRM2 can influence susceptibility to alcoholism [MIM:103780].

Involvement in disease

Major depressive disorder (MDD) [MIM:608516]: A common psychiatric disorder. It is a complex trait characterized by one or more major depressive episodes without a history of manic, mixed, or hypomanic episodes. A major depressive episode is characterized by at least 2 weeks during which there is a new onset or clear worsening of either depressed mood or loss of interest or pleasure in nearly all activities. Four additional symptoms must also be present including changes in appetite, weight, sleep, and psychomotor activity; decreased energy; feelings of worthlessness or guilt; difficulty thinking, concentrating, or making decisions; or recurrent thoughts of death or suicidal ideation, plans, or attempts. The episode must be accompanied by distress or impairment in social, occupational, or other important areas of functioning.
Note: Disease susceptibility is associated with variations affecting the gene represented in this entry.

Sequence similarities

Belongs to the G-protein coupled receptor 1 family. Muscarinic acetylcholine receptor subfamily. CHRM2 sub-subfamily.

Ontologies

Keywords
   Cellular componentCell junction
Cell membrane
Membrane
Postsynaptic cell membrane
Synapse
   DomainTransmembrane
Transmembrane helix
   Molecular functionG-protein coupled receptor
Receptor
Transducer
   PTMDisulfide bond
Glycoprotein
Phosphoprotein
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processG-protein coupled receptor signaling pathway

Traceable author statement PubMed 9603968. Source: ProtInc

G-protein coupled receptor signaling pathway, coupled to cyclic nucleotide second messenger

Traceable author statement PubMed 10895079. Source: ProtInc

adenylate cyclase-modulating G-protein coupled receptor signaling pathway

Traceable author statement PubMed 8139539. Source: ProtInc

nervous system development

Traceable author statement PubMed 2739737. Source: ProtInc

phospholipase C-activating G-protein coupled acetylcholine receptor signaling pathway

Traceable author statement PubMed 2739737. Source: ProtInc

regulation of heart contraction

Traceable author statement PubMed 10544184. Source: ProtInc

response to virus

Inferred from expression pattern Ref.7. Source: UniProtKB

   Cellular_componentcell junction

Inferred from electronic annotation. Source: UniProtKB-KW

integral component of plasma membrane

Traceable author statement Ref.1. Source: ProtInc

plasma membrane

Inferred from direct assay. Source: LIFEdb

postsynaptic membrane

Inferred from electronic annotation. Source: UniProtKB-SubCell

   Molecular_functionG-protein coupled acetylcholine receptor activity

Traceable author statement PubMed 9603968. Source: ProtInc

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 466466Muscarinic acetylcholine receptor M2
PRO_0000069021

Regions

Topological domain1 – 2222Extracellular By similarity
Transmembrane23 – 4523Helical; Name=1; By similarity
Topological domain46 – 5914Cytoplasmic By similarity
Transmembrane60 – 8021Helical; Name=2; By similarity
Topological domain81 – 9717Extracellular By similarity
Transmembrane98 – 11922Helical; Name=3; By similarity
Topological domain120 – 13920Cytoplasmic By similarity
Transmembrane140 – 16223Helical; Name=4; By similarity
Topological domain163 – 18422Extracellular By similarity
Transmembrane185 – 20723Helical; Name=5; By similarity
Topological domain208 – 388181Cytoplasmic By similarity
Transmembrane389 – 40921Helical; Name=6; By similarity
Topological domain410 – 42314Extracellular By similarity
Transmembrane424 – 44320Helical; Name=7; By similarity
Topological domain444 – 46623Cytoplasmic By similarity

Amino acid modifications

Modified residue4461Phosphothreonine Potential
Modified residue4501Phosphothreonine Potential
Modified residue4651Phosphothreonine Potential
Glycosylation21N-linked (GlcNAc...) Potential
Glycosylation31N-linked (GlcNAc...) Potential
Glycosylation61N-linked (GlcNAc...) Potential
Glycosylation91N-linked (GlcNAc...) Potential
Disulfide bond96 ↔ 176 By similarity

Secondary structure

.................................. 466
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
P08172 [UniParc].

Last modified August 1, 1988. Version 1.
Checksum: 2FC2FD7748C22BEC

FASTA46651,715
        10         20         30         40         50         60 
MNNSTNSSNN SLALTSPYKT FEVVFIVLVA GSLSLVTIIG NILVMVSIKV NRHLQTVNNY 

        70         80         90        100        110        120 
FLFSLACADL IIGVFSMNLY TLYTVIGYWP LGPVVCDLWL ALDYVVSNAS VMNLLIISFD 

       130        140        150        160        170        180 
RYFCVTKPLT YPVKRTTKMA GMMIAAAWVL SFILWAPAIL FWQFIVGVRT VEDGECYIQF 

       190        200        210        220        230        240 
FSNAAVTFGT AIAAFYLPVI IMTVLYWHIS RASKSRIKKD KKEPVANQDP VSPSLVQGRI 

       250        260        270        280        290        300 
VKPNNNNMPS SDDGLEHNKI QNGKAPRDPV TENCVQGEEK ESSNDSTSVS AVASNMRDDE 

       310        320        330        340        350        360 
ITQDENTVST SLGHSKDENS KQTCIRIGTK TPKSDSCTPT NTTVEVVGSS GQNGDEKQNI 

       370        380        390        400        410        420 
VARKIVKMTK QPAKKKPPPS REKKVTRTIL AILLAFIITW APYNVMVLIN TFCAPCIPNT 

       430        440        450        460 
VWTIGYWLCY INSTINPACY ALCNATFKKT FKHLLMCHYK NIGATR 

« Hide

References

« Hide 'large scale' references
[1]"Identification of a family of muscarinic acetylcholine receptor genes."
Bonner T.I., Buckley N.J., Young A.C., Brann M.R.
Science 237:527-532(1987) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[2]"Distinct primary structures, ligand-binding properties and tissue-specific expression of four human muscarinic acetylcholine receptors."
Peralta E.G., Ashkenazi A., Winslow J.W., Smith D.H., Ramachandran J., Capon D.J.
EMBO J. 6:3923-3929(1987) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[3]"cDNA clones of human proteins involved in signal transduction sequenced by the Guthrie cDNA resource center (www.cdna.org)."
Puhl H.L. III, Ikeda S.R., Aronstam R.S.
Submitted (APR-2002) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Tissue: Brain.
[4]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[5]"Human-specific amino acid changes found in 103 protein-coding genes."
Kitano T., Liu Y.-H., Ueda S., Saitou N.
Mol. Biol. Evol. 21:936-944(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 27-466.
[6]"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."
Gurevich V.V., Dion S.B., Onorato J.J., Ptasienski J., Kim C.M., Sterne-Marr R., Hosey M.M., Benovic J.L.
J. Biol. Chem. 270:720-731(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH ARRB1 AND ARRB2.
[7]"Transcriptomic and proteomic analyses of rhabdomyosarcoma cells reveal differential cellular gene expression in response to enterovirus 71 infection."
Leong W.F., Chow V.T.
Cell. Microbiol. 8:565-580(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: INDUCTION, IDENTIFICATION BY MASS SPECTROMETRY.
[8]"Evidence of common and specific genetic effects: association of the muscarinic acetylcholine receptor M2 (CHRM2) gene with alcohol dependence and major depressive syndrome."
Wang J.C., Hinrichs A.L., Stock H., Budde J., Allen R., Bertelsen S., Kwon J.M., Wu W., Dick D.M., Rice J., Jones K., Nurnberger J.I. Jr., Tischfield J., Porjesz B., Edenberg H.J., Hesselbrock V., Crowe R., Schuckit M. expand/collapse author list , Begleiter H., Reich T., Goate A.M., Bierut L.J.
Hum. Mol. Genet. 13:1903-1911(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: INVOLVEMENT IN SUSCEPTIBILITY TO ALCOHOLISM AND MAJOR DEPRESSIVE DISORDER.
[9]"RACK1 associates with muscarinic receptors and regulates M(2) receptor trafficking."
Reiner C.L., McCullar J.S., Kow R.L., Le J.H., Goodlett D.R., Nathanson N.M.
PLoS ONE 5:E13517-E13517(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH GNB2L1.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
M16404 Genomic DNA. Translation: AAA51570.1.
X15264 Genomic DNA. Translation: CAA33335.1.
AF498916 mRNA. Translation: AAM18939.1.
BC095547 mRNA. Translation: AAH95547.1.
BC106741 mRNA. Translation: AAI06742.1.
BC106742 mRNA. Translation: AAI06743.1.
AB041391 Genomic DNA. Translation: BAA94476.1.
CCDSCCDS5843.1.
PIRS10126.
RefSeqNP_000730.1. NM_000739.2.
NP_001006627.1. NM_001006626.1.
NP_001006628.1. NM_001006627.1.
NP_001006629.1. NM_001006628.1.
NP_001006630.1. NM_001006629.1.
NP_001006631.1. NM_001006630.1.
NP_001006632.1. NM_001006631.1.
NP_001006633.1. NM_001006632.1.
UniGeneHs.535891.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1LUBmodel-A1-50[»]
3UONX-ray3.00A1-217[»]
A377-466[»]
4MQSX-ray3.50A1-466[»]
4MQTX-ray3.70A1-466[»]
ProteinModelPortalP08172.
SMRP08172. Positions 20-217, 377-456.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid107551. 4 interactions.
IntActP08172. 4 interactions.
STRING9606.ENSP00000319984.

Chemistry

BindingDBP08172.
ChEMBLCHEMBL2095187.
DrugBankDB00517. Anisotropine Methylbromide.
DB00572. Atropine.
DB00767. Benzquinamide.
DB00411. Carbachol.
DB00785. Cryptenamine.
DB01176. Cyclizine.
DB01151. Desipramine.
DB01231. Diphenidol.
DB01334. Doxacurium.
DB01135. Doxacurium chloride.
DB01148. Flavoxate.
DB00483. Gallamine Triethiodide.
DB00725. Homatropine Methylbromide.
DB00424. Hyoscyamine.
DB00332. Ipratropium.
DB01403. Methotrimeprazine.
DB00340. Metixene.
DB01336. Metocurine.
DB01226. Mivacurium.
DB00334. Olanzapine.
DB01062. Oxybutynin.
DB00383. Oxyphencyclimine.
DB01085. Pilocarpine.
DB00387. Procyclidine.
DB00420. Promazine.
DB01069. Promethazine.
DB00777. Propiomazine.
DB00728. Rocuronium.
DB00372. Thiethylperazine.
DB01036. Tolterodine.
DB00505. Tridihexethyl.
DB00508. Triflupromazine.
GuidetoPHARMACOLOGY14.

Protein family/group databases

GPCRDBSearch...

PTM databases

PhosphoSiteP08172.

Polymorphism databases

DMDM113122.

Proteomic databases

PaxDbP08172.
PRIDEP08172.

Protocols and materials databases

DNASU1129.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000320658; ENSP00000319984; ENSG00000181072.
ENST00000397608; ENSP00000380733; ENSG00000181072.
ENST00000401861; ENSP00000384401; ENSG00000181072.
ENST00000402486; ENSP00000384937; ENSG00000181072.
ENST00000445907; ENSP00000399745; ENSG00000181072.
ENST00000453373; ENSP00000415386; ENSG00000181072.
GeneID1129.
KEGGhsa:1129.
UCSCuc003vtf.1. human.

Organism-specific databases

CTD1129.
GeneCardsGC07P136553.
HGNCHGNC:1951. CHRM2.
HPACAB022338.
HPA029795.
MIM103780. phenotype.
118493. gene.
608516. phenotype.
neXtProtNX_P08172.
PharmGKBPA111.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG250863.
HOGENOMHOG000231484.
HOVERGENHBG105720.
InParanoidP08172.
KOK04130.
OMANNNMPGS.
OrthoDBEOG7V49Z7.
PhylomeDBP08172.
TreeFamTF320495.

Enzyme and pathway databases

ReactomeREACT_111102. Signal Transduction.
SignaLinkP08172.

Gene expression databases

ArrayExpressP08172.
BgeeP08172.
CleanExHS_CHRM2.
GenevestigatorP08172.

Family and domain databases

Gene3D1.20.1070.10. 2 hits.
InterProIPR000276. GPCR_Rhodpsn.
IPR017452. GPCR_Rhodpsn_7TM.
IPR001065. Musac_Ach_M2_rcpt.
IPR000995. Musac_Ach_rcpt.
[Graphical view]
PANTHERPTHR24249:SF57. PTHR24249:SF57. 1 hit.
PfamPF00001. 7tm_1. 1 hit.
[Graphical view]
PRINTSPR00237. GPCRRHODOPSN.
PR00243. MUSCARINICR.
PR00539. MUSCRINICM2R.
PROSITEPS00237. G_PROTEIN_RECEP_F1_1. 1 hit.
PS50262. G_PROTEIN_RECEP_F1_2. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

GeneWikiMuscarinic_acetylcholine_receptor_M2.
GenomeRNAi1129.
NextBio4680.
PROP08172.
SOURCESearch...

Entry information

Entry nameACM2_HUMAN
AccessionPrimary (citable) accession number: P08172
Secondary accession number(s): Q4VBK6, Q9P1X9
Entry history
Integrated into UniProtKB/Swiss-Prot: August 1, 1988
Last sequence update: August 1, 1988
Last modified: July 9, 2014
This is version 152 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human chromosome 7

Human chromosome 7: entries, gene names and cross-references to MIM

7-transmembrane G-linked receptors

List of 7-transmembrane G-linked receptor entries