P08172 (ACM2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Muscarinic acetylcholine receptor M2

Gene names

Name:

CHRM2

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	466 AA.
Sequence status	Complete.
Protein existence	Evidence 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 junction › synapse › postsynaptic 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 component	Cell junction Cell membrane Membrane Postsynaptic cell membrane Synapse
Domain	Transmembrane Transmembrane helix
Molecular function	G-protein coupled receptor Receptor Transducer
PTM	Disulfide bond Glycoprotein Phosphoprotein
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	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_component	cell junction Inferred from electronic annotation. Source: UniProtKB-KW integral to plasma membrane Traceable author statement Ref.1. Source: ProtInc postsynaptic membrane Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular_function	G-protein coupled acetylcholine receptor activity Traceable author statement PubMed 9603968. Source: ProtInc
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 466

466

Muscarinic acetylcholine receptor M2

PRO_0000069021

Regions

Topological domain

1 – 22

22

Extracellular By similarity

Transmembrane

23 – 45

23

Helical; Name=1; By similarity

Topological domain

46 – 59

14

Cytoplasmic By similarity

Transmembrane

60 – 80

21

Helical; Name=2; By similarity

Topological domain

81 – 97

17

Extracellular By similarity

Transmembrane

98 – 119

22

Helical; Name=3; By similarity

Topological domain

120 – 139

20

Cytoplasmic By similarity

Transmembrane

140 – 162

23

Helical; Name=4; By similarity

Topological domain

163 – 184

22

Extracellular By similarity

Transmembrane

185 – 207

23

Helical; Name=5; By similarity

Topological domain

208 – 388

181

Cytoplasmic By similarity

Transmembrane

389 – 409

21

Helical; Name=6; By similarity

Topological domain

410 – 423

14

Extracellular By similarity

Transmembrane

424 – 443

20

Helical; Name=7; By similarity

Topological domain

444 – 466

23

Cytoplasmic By similarity

Amino acid modifications

Modified residue

232

1

Phosphoserine By similarity

Modified residue

234

1

Phosphoserine By similarity

Modified residue

446

1

Phosphothreonine Potential

Modified residue

450

1

Phosphothreonine Potential

Modified residue

465

1

Phosphothreonine Potential

Glycosylation

2

1

N-linked (GlcNAc...) Potential

Glycosylation

3

1

N-linked (GlcNAc...) Potential

Glycosylation

6

1

N-linked (GlcNAc...) Potential

Glycosylation

9

1

N-linked (GlcNAc...) Potential

Disulfide bond

96 ↔ 176

By similarity

Secondary structure

1

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466

Helix Strand Turn

Details...

Helix

23 – 50

28

Helix

52 – 54

3

Helix

57 – 74

18

Helix

76 – 85

10

Beta strand

86 – 88

3

Helix

93 – 126

34

Turn

128 – 130

3

Helix

132 – 134

3

Helix

137 – 166

30

Helix

179 – 182

4

Helix

184 – 194

11

Helix

196 – 213

18

Helix

384 – 412

29

Helix

419 – 431

13

Turn

432 – 434

3

Helix

435 – 443

9

Helix

445 – 454

10

Sequences

	Sequence		Length	Mass (Da)
	P08172 [UniParc]. Last modified August 1, 1988. Version 1. Checksum: 2FC2FD7748C22BEC	FASTA	466	51,715
	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

References

	« Hide 'large scale' referencesShow '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, 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. , 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.

IPI

IPI00027473.

PIR

S10126.

RefSeq

NP_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.

UniGene

Hs.535891.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1LUB	model	-	A	1-50	[»]
3UON	X-ray	3.00	A	4-466	[»]

ProteinModelPortal

P08172.

ModBase

Search...

Protein-protein interaction databases

IntAct

P08172. 4 interactions.

STRING

9606.ENSP00000319984.

Protein family/group databases

GPCRDB

Search...

PTM databases

PhosphoSite

P08172.

Polymorphism databases

DMDM

113122.

Proteomic databases

PaxDb

P08172.

PRIDE

P08172.

Protocols and materials databases

DNASU

1129.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000320658; ENSP00000319984; ENSG00000181072.
ENST00000397608; ENSP00000380733; ENSG00000181072.
ENST00000401861; ENSP00000384401; ENSG00000181072.
ENST00000402486; ENSP00000384937; ENSG00000181072.
ENST00000445907; ENSP00000399745; ENSG00000181072.
ENST00000453373; ENSP00000415386; ENSG00000181072.

GeneID

1129.

KEGG

hsa:1129.

UCSC

uc003vtf.1. human.

Organism-specific databases

CTD

1129.

GeneCards

GC07P136553.

HGNC

HGNC:1951. CHRM2.

HPA

CAB022338.
HPA029795.

MIM

103780. phenotype.
118493. gene.
608516. phenotype.

neXtProt

NX_P08172.

PharmGKB

PA111.

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG250863.

HOGENOM

HOG000231484.

HOVERGEN

HBG105720.

InParanoid

P08172.

KO

K04130.

OMA

NNNMPGS.

OrthoDB

EOG41JZCC.

PhylomeDB

P08172.

Enzyme and pathway databases

Pathway_Interaction_DB

arf6_traffickingpathway. Arf6 trafficking events.

Reactome

REACT_111102. Signal Transduction.

Gene expression databases

ArrayExpress

P08172.

Bgee

P08172.

CleanEx

HS_CHRM2.

Genevestigator

P08172.

GermOnline

ENSG00000181072. Homo sapiens.

Family and domain databases

InterPro

IPR000276. GPCR_Rhodpsn.
IPR017452. GPCR_Rhodpsn_7TM.
IPR001065. Musac_M2_rcpt.
IPR000995. Musac_rcpt.
[Graphical view]

Pfam

PF00001. 7tm_1. 1 hit.
[Graphical view]

PRINTS

PR00237. GPCRRHODOPSN.
PR00243. MUSCARINICR.
PR00539. MUSCRINICM2R.

PROSITE

PS00237. G_PROTEIN_RECEP_F1_1. 1 hit.
PS50262. G_PROTEIN_RECEP_F1_2. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

BindingDB

P08172.

ChEMBL

CHEMBL211.

DrugBank

DB00517. 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.

GenomeRNAi

1129.

NextBio

4680.

SOURCE

Search...

Entry information

Entry name

ACM2_HUMAN

Accession

Primary (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:	May 1, 2013
This is version 140 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.