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P08172

- ACM2_HUMAN

UniProt

P08172 - ACM2_HUMAN

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Protein
Muscarinic acetylcholine receptor M2
Gene
CHRM2
Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5 - Experimental evidence at protein leveli

Functioni

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.

GO - Molecular functioni

  1. G-protein coupled acetylcholine receptor activity Source: ProtInc
Complete GO annotation...

GO - Biological processi

  1. G-protein coupled receptor signaling pathway Source: ProtInc
  2. G-protein coupled receptor signaling pathway, coupled to cyclic nucleotide second messenger Source: ProtInc
  3. adenylate cyclase-modulating G-protein coupled receptor signaling pathway Source: ProtInc
  4. nervous system development Source: ProtInc
  5. phospholipase C-activating G-protein coupled acetylcholine receptor signaling pathway Source: ProtInc
  6. regulation of heart contraction Source: ProtInc
  7. response to virus Source: UniProtKB
Complete GO annotation...

Keywords - Molecular functioni

G-protein coupled receptor, Receptor, Transducer

Enzyme and pathway databases

ReactomeiREACT_16943. Muscarinic acetylcholine receptors.
REACT_19231. G alpha (i) signalling events.
SignaLinkiP08172.

Names & Taxonomyi

Protein namesi
Recommended name:
Muscarinic acetylcholine receptor M2
Gene namesi
Name:CHRM2
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640: Chromosome 7

Organism-specific databases

HGNCiHGNC:1951. CHRM2.

Subcellular locationi

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini1 – 2222Extracellular By similarity
Add
BLAST
Transmembranei23 – 4523Helical; Name=1; By similarity
Add
BLAST
Topological domaini46 – 5914Cytoplasmic By similarity
Add
BLAST
Transmembranei60 – 8021Helical; Name=2; By similarity
Add
BLAST
Topological domaini81 – 9717Extracellular By similarity
Add
BLAST
Transmembranei98 – 11922Helical; Name=3; By similarity
Add
BLAST
Topological domaini120 – 13920Cytoplasmic By similarity
Add
BLAST
Transmembranei140 – 16223Helical; Name=4; By similarity
Add
BLAST
Topological domaini163 – 18422Extracellular By similarity
Add
BLAST
Transmembranei185 – 20723Helical; Name=5; By similarity
Add
BLAST
Topological domaini208 – 388181Cytoplasmic By similarity
Add
BLAST
Transmembranei389 – 40921Helical; Name=6; By similarity
Add
BLAST
Topological domaini410 – 42314Extracellular By similarity
Add
BLAST
Transmembranei424 – 44320Helical; Name=7; By similarity
Add
BLAST
Topological domaini444 – 46623Cytoplasmic By similarity
Add
BLAST

GO - Cellular componenti

  1. cell junction Source: UniProtKB-KW
  2. integral component of plasma membrane Source: ProtInc
  3. plasma membrane Source: LIFEdb
  4. postsynaptic membrane Source: UniProtKB-SubCell
Complete GO annotation...

Keywords - Cellular componenti

Cell junction, Cell membrane, Membrane, Postsynaptic cell membrane, Synapse

Pathology & Biotechi

Involvement in diseasei

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.

Organism-specific databases

MIMi103780. phenotype.
608516. phenotype.
PharmGKBiPA111.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 466466Muscarinic acetylcholine receptor M2
PRO_0000069021Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Glycosylationi2 – 21N-linked (GlcNAc...) Reviewed prediction
Glycosylationi3 – 31N-linked (GlcNAc...) Reviewed prediction
Glycosylationi6 – 61N-linked (GlcNAc...) Reviewed prediction
Glycosylationi9 – 91N-linked (GlcNAc...) Reviewed prediction
Disulfide bondi96 ↔ 176 By similarity
Modified residuei446 – 4461Phosphothreonine Reviewed prediction
Modified residuei450 – 4501Phosphothreonine Reviewed prediction
Modified residuei465 – 4651Phosphothreonine Reviewed prediction

Keywords - PTMi

Disulfide bond, Glycoprotein, Phosphoprotein

Proteomic databases

PaxDbiP08172.
PRIDEiP08172.

PTM databases

PhosphoSiteiP08172.

Expressioni

Inductioni

Up-regulated in response to enterovirus 71 (EV71) infection.1 Publication

Gene expression databases

ArrayExpressiP08172.
BgeeiP08172.
CleanExiHS_CHRM2.
GenevestigatoriP08172.

Organism-specific databases

HPAiCAB022338.
HPA029795.

Interactioni

Subunit structurei

Interacts with ARRB1 and ARRB2. Interacts with GNB2L1/RACK1; the interaction regulates CHRM2 internalization.2 Publications

Protein-protein interaction databases

BioGridi107551. 4 interactions.
IntActiP08172. 4 interactions.
STRINGi9606.ENSP00000319984.

Structurei

Secondary structure

Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Helixi23 – 5028
Helixi52 – 543
Helixi57 – 7418
Helixi76 – 8510
Beta strandi86 – 883
Helixi93 – 12634
Turni128 – 1303
Helixi132 – 1343
Helixi137 – 16630
Helixi179 – 1824
Helixi184 – 19411
Helixi196 – 21318
Helixi384 – 41229
Helixi414 – 4163
Helixi419 – 43113
Turni432 – 4343
Helixi435 – 4439
Helixi445 – 45410

3D structure databases

Select the link destinations:
PDBe
RCSB PDB
PDBj
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
1LUBmodel-A1-50[»]
3UONX-ray3.00A1-217[»]
A377-466[»]
4MQSX-ray3.50A1-466[»]
4MQTX-ray3.70A1-466[»]
ProteinModelPortaliP08172.
SMRiP08172. Positions 20-217, 377-456.

Family & Domainsi

Sequence similaritiesi

Keywords - Domaini

Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiNOG250863.
HOGENOMiHOG000231484.
HOVERGENiHBG105720.
InParanoidiP08172.
KOiK04130.
OMAiNNNMPGS.
OrthoDBiEOG7V49Z7.
PhylomeDBiP08172.
TreeFamiTF320495.

Family and domain databases

Gene3Di1.20.1070.10. 2 hits.
InterProiIPR000276. GPCR_Rhodpsn.
IPR017452. GPCR_Rhodpsn_7TM.
IPR001065. Musac_Ach_M2_rcpt.
IPR000995. Musac_Ach_rcpt.
[Graphical view]
PANTHERiPTHR24249:SF57. PTHR24249:SF57. 1 hit.
PfamiPF00001. 7tm_1. 1 hit.
[Graphical view]
PRINTSiPR00237. GPCRRHODOPSN.
PR00243. MUSCARINICR.
PR00539. MUSCRINICM2R.
PROSITEiPS00237. G_PROTEIN_RECEP_F1_1. 1 hit.
PS50262. G_PROTEIN_RECEP_F1_2. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

P08172-1 [UniParc]FASTAAdd to Basket

« Hide

MNNSTNSSNN SLALTSPYKT FEVVFIVLVA GSLSLVTIIG NILVMVSIKV    50
NRHLQTVNNY FLFSLACADL IIGVFSMNLY TLYTVIGYWP LGPVVCDLWL 100
ALDYVVSNAS VMNLLIISFD RYFCVTKPLT YPVKRTTKMA GMMIAAAWVL 150
SFILWAPAIL FWQFIVGVRT VEDGECYIQF FSNAAVTFGT AIAAFYLPVI 200
IMTVLYWHIS RASKSRIKKD KKEPVANQDP VSPSLVQGRI VKPNNNNMPS 250
SDDGLEHNKI QNGKAPRDPV TENCVQGEEK ESSNDSTSVS AVASNMRDDE 300
ITQDENTVST SLGHSKDENS KQTCIRIGTK TPKSDSCTPT NTTVEVVGSS 350
GQNGDEKQNI VARKIVKMTK QPAKKKPPPS REKKVTRTIL AILLAFIITW 400
APYNVMVLIN TFCAPCIPNT VWTIGYWLCY INSTINPACY ALCNATFKKT 450
FKHLLMCHYK NIGATR 466
Length:466
Mass (Da):51,715
Last modified:August 1, 1988 - v1
Checksum:i2FC2FD7748C22BEC
GO

Polymorphismi

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

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
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.
CCDSiCCDS5843.1.
PIRiS10126.
RefSeqiNP_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.
UniGeneiHs.535891.

Genome annotation databases

EnsembliENST00000320658; ENSP00000319984; ENSG00000181072.
ENST00000397608; ENSP00000380733; ENSG00000181072.
ENST00000401861; ENSP00000384401; ENSG00000181072.
ENST00000402486; ENSP00000384937; ENSG00000181072.
ENST00000445907; ENSP00000399745; ENSG00000181072.
ENST00000453373; ENSP00000415386; ENSG00000181072.
GeneIDi1129.
KEGGihsa:1129.
UCSCiuc003vtf.1. human.

Polymorphism databases

DMDMi113122.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
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 .
CCDSi CCDS5843.1.
PIRi S10126.
RefSeqi 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.
UniGenei Hs.535891.

3D structure databases

Select the link destinations:
PDBe
RCSB PDB
PDBj
Links Updated
Entry Method Resolution (Å) Chain Positions PDBsum
1LUB model - A 1-50 [» ]
3UON X-ray 3.00 A 1-217 [» ]
A 377-466 [» ]
4MQS X-ray 3.50 A 1-466 [» ]
4MQT X-ray 3.70 A 1-466 [» ]
ProteinModelPortali P08172.
SMRi P08172. Positions 20-217, 377-456.
ModBasei Search...

Protein-protein interaction databases

BioGridi 107551. 4 interactions.
IntActi P08172. 4 interactions.
STRINGi 9606.ENSP00000319984.

Chemistry

BindingDBi P08172.
ChEMBLi CHEMBL2095187.
DrugBanki 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.
GuidetoPHARMACOLOGYi 14.

Protein family/group databases

GPCRDBi Search...

PTM databases

PhosphoSitei P08172.

Polymorphism databases

DMDMi 113122.

Proteomic databases

PaxDbi P08172.
PRIDEi P08172.

Protocols and materials databases

DNASUi 1129.
Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENST00000320658 ; ENSP00000319984 ; ENSG00000181072 .
ENST00000397608 ; ENSP00000380733 ; ENSG00000181072 .
ENST00000401861 ; ENSP00000384401 ; ENSG00000181072 .
ENST00000402486 ; ENSP00000384937 ; ENSG00000181072 .
ENST00000445907 ; ENSP00000399745 ; ENSG00000181072 .
ENST00000453373 ; ENSP00000415386 ; ENSG00000181072 .
GeneIDi 1129.
KEGGi hsa:1129.
UCSCi uc003vtf.1. human.

Organism-specific databases

CTDi 1129.
GeneCardsi GC07P136553.
HGNCi HGNC:1951. CHRM2.
HPAi CAB022338.
HPA029795.
MIMi 103780. phenotype.
118493. gene.
608516. phenotype.
neXtProti NX_P08172.
PharmGKBi PA111.
GenAtlasi Search...

Phylogenomic databases

eggNOGi NOG250863.
HOGENOMi HOG000231484.
HOVERGENi HBG105720.
InParanoidi P08172.
KOi K04130.
OMAi NNNMPGS.
OrthoDBi EOG7V49Z7.
PhylomeDBi P08172.
TreeFami TF320495.

Enzyme and pathway databases

Reactomei REACT_16943. Muscarinic acetylcholine receptors.
REACT_19231. G alpha (i) signalling events.
SignaLinki P08172.

Miscellaneous databases

GeneWikii Muscarinic_acetylcholine_receptor_M2.
GenomeRNAii 1129.
NextBioi 4680.
PROi P08172.
SOURCEi Search...

Gene expression databases

ArrayExpressi P08172.
Bgeei P08172.
CleanExi HS_CHRM2.
Genevestigatori P08172.

Family and domain databases

Gene3Di 1.20.1070.10. 2 hits.
InterProi IPR000276. GPCR_Rhodpsn.
IPR017452. GPCR_Rhodpsn_7TM.
IPR001065. Musac_Ach_M2_rcpt.
IPR000995. Musac_Ach_rcpt.
[Graphical view ]
PANTHERi PTHR24249:SF57. PTHR24249:SF57. 1 hit.
Pfami PF00001. 7tm_1. 1 hit.
[Graphical view ]
PRINTSi PR00237. GPCRRHODOPSN.
PR00243. MUSCARINICR.
PR00539. MUSCRINICM2R.
PROSITEi PS00237. G_PROTEIN_RECEP_F1_1. 1 hit.
PS50262. G_PROTEIN_RECEP_F1_2. 1 hit.
[Graphical view ]
ProtoNeti Search...

Publicationsi

« Hide 'large scale' publications
  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.
    , 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.

Entry informationi

Entry nameiACM2_HUMAN
AccessioniPrimary (citable) accession number: P08172
Secondary accession number(s): Q4VBK6, Q9P1X9
Entry historyi
Integrated into UniProtKB/Swiss-Prot: August 1, 1988
Last sequence update: August 1, 1988
Last modified: September 3, 2014
This is version 153 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (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.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. 7-transmembrane G-linked receptors
    List of 7-transmembrane G-linked receptor entries
  2. Human chromosome 7
    Human chromosome 7: entries, gene names and cross-references to MIM
  3. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  4. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  5. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

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