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Protein

Muscarinic acetylcholine receptor M2

Gene

CHRM2

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -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. Signaling promotes phospholipase C activity, leading to the release of inositol trisphosphate (IP3); this then triggers calcium ion release into the cytosol.2 Publications

GO - Molecular functioni

  • arrestin family protein binding Source: CAFA
  • drug binding Source: Ensembl
  • G protein-coupled acetylcholine receptor activity Source: UniProtKB
  • G protein-coupled receptor activity Source: GO_Central
  • G protein-coupled serotonin receptor activity Source: GO_Central
  • neurotransmitter receptor activity Source: GO_Central

GO - Biological processi

Keywordsi

Molecular functionG-protein coupled receptor, Receptor, Transducer

Enzyme and pathway databases

ReactomeiR-HSA-390648 Muscarinic acetylcholine receptors
R-HSA-418594 G alpha (i) signalling events
R-HSA-8856825 Cargo recognition for clathrin-mediated endocytosis
R-HSA-8856828 Clathrin-mediated endocytosis
SignaLinkiP08172
SIGNORiP08172

Names & Taxonomyi

Protein namesi
Recommended name:
Muscarinic acetylcholine receptor M2
Gene namesi
Name:CHRM2
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 7

Organism-specific databases

EuPathDBiHostDB:ENSG00000181072.11
HGNCiHGNC:1951 CHRM2
MIMi118493 gene
neXtProtiNX_P08172

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini1 – 22ExtracellularAdd BLAST22
Transmembranei23 – 45Helical; Name=1Add BLAST23
Topological domaini46 – 59CytoplasmicAdd BLAST14
Transmembranei60 – 80Helical; Name=2Add BLAST21
Topological domaini81 – 97ExtracellularAdd BLAST17
Transmembranei98 – 119Helical; Name=3Add BLAST22
Topological domaini120 – 139CytoplasmicAdd BLAST20
Transmembranei140 – 162Helical; Name=4Add BLAST23
Topological domaini163 – 184ExtracellularAdd BLAST22
Transmembranei185 – 209Helical; Name=5Add BLAST25
Topological domaini210 – 387CytoplasmicAdd BLAST178
Transmembranei388 – 410Helical; Name=6Add BLAST23
Topological domaini411 – 418Extracellular8
Transmembranei419 – 442Helical; Name=7Add BLAST24
Topological domaini443 – 466CytoplasmicAdd BLAST24

Keywords - Cellular componenti

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

Pathology & Biotechi

Involvement in diseasei

Major depressive disorder (MDD)1 Publication
Disease susceptibility is associated with variations affecting the gene represented in this entry.
Disease descriptionA 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.
See also OMIM:608516

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi58N → A: Nearly abolishes signaling via downstream effectors. 1 Publication1
Mutagenesisi103D → E: Reduced affinity for acetylcholine. Abolishes signaling via downstream effectors. 1 Publication1
Mutagenesisi206Y → F: Abolishes signaling via downstream effectors. 1 Publication1
Mutagenesisi404N → Q: Reduced affinity for acetylcholine. Reduces signaling via downstream effectors. 1 Publication1

Organism-specific databases

DisGeNETi1129
MIMi103780 phenotype
608516 phenotype
OpenTargetsiENSG00000181072
PharmGKBiPA111

Chemistry databases

ChEMBLiCHEMBL211
DrugBankiDB08897 Aclidinium
DB05752 ALKS 27
DB00321 Amitriptyline
DB00543 Amoxapine
DB00517 Anisotropine Methylbromide
DB01238 Aripiprazole
DB00572 Atropine
DB00767 Benzquinamide
DB01019 Bethanechol
DB00835 Brompheniramine
DB00411 Carbachol
DB01239 Chlorprothixene
DB00568 Cinnarizine
DB00363 Clozapine
DB00907 Cocaine
DB00785 Cryptenamine
DB00434 Cyproheptadine
DB00496 Darifenacin
DB01151 Desipramine
DB00804 Dicyclomine
DB08801 Dimetindene
DB01075 Diphenhydramine
DB01231 Diphenidol
DB00280 Disopyramide
DB01135 Doxacurium chloride
DB01142 Doxepin
DB00392 Ethopropazine
DB06702 Fesoterodine
DB01148 Flavoxate
DB00483 Gallamine Triethiodide
DB00986 Glycopyrronium
DB00725 Homatropine Methylbromide
DB00424 Hyoscyamine
DB00458 Imipramine
DB00332 Ipratropium bromide
DB01221 Ketamine
DB00408 Loxapine
DB00934 Maprotiline
DB01403 Methotrimeprazine
DB00462 Methylscopolamine bromide
DB00340 Metixene
DB01336 Metocurine
DB01226 Mivacurium
DB00622 Nicardipine
DB00540 Nortriptyline
DB00334 Olanzapine
DB01062 Oxybutynin
DB00383 Oxyphencyclimine
DB01337 Pancuronium
DB00715 Paroxetine
DB00454 Pethidine
DB01085 Pilocarpine
DB01338 Pipecuronium
DB00387 Procyclidine
DB00420 Promazine
DB01069 Promethazine
DB00777 Propiomazine
DB01224 Quetiapine
DB00728 Rocuronium
DB00747 Scopolamine
DB01591 Solifenacin
DB00202 Succinylcholine
DB00342 Terfenadine
DB01409 Tiotropium
DB01036 Tolterodine
DB00505 Tridihexethyl
DB00508 Triflupromazine
DB00376 Trihexyphenidyl
DB00726 Trimipramine
DB00809 Tropicamide
DB09076 Umeclidinium
DB00246 Ziprasidone
GuidetoPHARMACOLOGYi14

Polymorphism and mutation databases

BioMutaiCHRM2
DMDMi113122

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000690211 – 466Muscarinic acetylcholine receptor M2Add BLAST466

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi2N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi3N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi6N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi9N-linked (GlcNAc...) asparagineSequence analysis1
Disulfide bondi96 ↔ 176
Modified residuei232PhosphoserineBy similarity1
Disulfide bondi413 ↔ 416
Modified residuei446PhosphothreonineSequence analysis1
Modified residuei450PhosphothreonineSequence analysis1
Modified residuei465PhosphothreonineSequence analysis1

Post-translational modificationi

Phosphorylated in response to agonist treatment.By similarity

Keywords - PTMi

Disulfide bond, Glycoprotein, Phosphoprotein

Proteomic databases

PaxDbiP08172
PeptideAtlasiP08172
PRIDEiP08172
ProteomicsDBi52076

PTM databases

iPTMnetiP08172
PhosphoSitePlusiP08172
SwissPalmiP08172

Expressioni

Inductioni

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

Gene expression databases

BgeeiENSG00000181072 Expressed in 60 organ(s), highest expression level in heart
CleanExiHS_CHRM2
ExpressionAtlasiP08172 baseline and differential
GenevisibleiP08172 HS

Organism-specific databases

HPAiCAB022338
HPA029795

Interactioni

Subunit structurei

Interacts with ARRB1 and ARRB2. Interacts with RACK1; the interaction regulates CHRM2 internalization.3 Publications

GO - Molecular functioni

Protein-protein interaction databases

BioGridi107551, 4 interactors
DIPiDIP-56282N
IntActiP08172, 14 interactors
MINTiP08172
STRINGi9606.ENSP00000319984

Chemistry databases

BindingDBiP08172

Structurei

Secondary structure

1466
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

ProteinModelPortaliP08172
SMRiP08172
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni103 – 107Agonist bindingCurated5
Regioni403 – 404Agonist bindingCurated2
Regioni426 – 430Agonist bindingCurated5

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi120 – 122Important for signaling3
Motifi436 – 440Important for signaling5

Sequence similaritiesi

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

Keywords - Domaini

Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG4220 Eukaryota
ENOG410YCQR LUCA
GeneTreeiENSGT00780000121874
HOGENOMiHOG000231484
HOVERGENiHBG105720
InParanoidiP08172
KOiK04130
OMAiCIKIVTK
OrthoDBiEOG091G06VI
PhylomeDBiP08172
TreeFamiTF320495

Family and domain databases

CDDicd15297 7tmA_mAChR_M2, 1 hit
InterProiView protein in InterPro
IPR000276 GPCR_Rhodpsn
IPR017452 GPCR_Rhodpsn_7TM
IPR001065 Musac_Ach_M2_rcpt
IPR000995 Musac_Ach_rcpt
PfamiView protein in Pfam
PF00001 7tm_1, 1 hit
PRINTSiPR00237 GPCRRHODOPSN
PR00243 MUSCARINICR
PR00539 MUSCRINICM2R
SMARTiView protein in SMART
SM01381 7TM_GPCR_Srsx, 1 hit
PROSITEiView protein in PROSITE
PS00237 G_PROTEIN_RECEP_F1_1, 1 hit
PS50262 G_PROTEIN_RECEP_F1_2, 1 hit

Sequencei

Sequence statusi: Complete.

P08172-1 [UniParc]FASTAAdd to basket
« Hide
        10         20         30         40         50
MNNSTNSSNN SLALTSPYKT FEVVFIVLVA GSLSLVTIIG NILVMVSIKV
60 70 80 90 100
NRHLQTVNNY FLFSLACADL IIGVFSMNLY TLYTVIGYWP LGPVVCDLWL
110 120 130 140 150
ALDYVVSNAS VMNLLIISFD RYFCVTKPLT YPVKRTTKMA GMMIAAAWVL
160 170 180 190 200
SFILWAPAIL FWQFIVGVRT VEDGECYIQF FSNAAVTFGT AIAAFYLPVI
210 220 230 240 250
IMTVLYWHIS RASKSRIKKD KKEPVANQDP VSPSLVQGRI VKPNNNNMPS
260 270 280 290 300
SDDGLEHNKI QNGKAPRDPV TENCVQGEEK ESSNDSTSVS AVASNMRDDE
310 320 330 340 350
ITQDENTVST SLGHSKDENS KQTCIRIGTK TPKSDSCTPT NTTVEVVGSS
360 370 380 390 400
GQNGDEKQNI VARKIVKMTK QPAKKKPPPS REKKVTRTIL AILLAFIITW
410 420 430 440 450
APYNVMVLIN TFCAPCIPNT VWTIGYWLCY INSTINPACY ALCNATFKKT
460
FKHLLMCHYK NIGATR
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].1 Publication

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
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
XP_011514071.1, XM_011515769.2
UniGeneiHs.535891

Genome annotation databases

EnsembliENST00000320658; ENSP00000319984; ENSG00000181072
ENST00000401861; ENSP00000384401; ENSG00000181072
ENST00000445907; ENSP00000399745; ENSG00000181072
ENST00000453373; ENSP00000415386; ENSG00000181072
GeneIDi1129
KEGGihsa:1129
UCSCiuc003vtg.2 human

Similar proteinsi

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
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
XP_011514071.1, XM_011515769.2
UniGeneiHs.535891

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1LUBmodel-A1-50[»]
3UONX-ray3.00A1-217[»]
A377-466[»]
4MQSX-ray3.50A1-466[»]
4MQTX-ray3.70A1-466[»]
ProteinModelPortaliP08172
SMRiP08172
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi107551, 4 interactors
DIPiDIP-56282N
IntActiP08172, 14 interactors
MINTiP08172
STRINGi9606.ENSP00000319984

Chemistry databases

BindingDBiP08172
ChEMBLiCHEMBL211
DrugBankiDB08897 Aclidinium
DB05752 ALKS 27
DB00321 Amitriptyline
DB00543 Amoxapine
DB00517 Anisotropine Methylbromide
DB01238 Aripiprazole
DB00572 Atropine
DB00767 Benzquinamide
DB01019 Bethanechol
DB00835 Brompheniramine
DB00411 Carbachol
DB01239 Chlorprothixene
DB00568 Cinnarizine
DB00363 Clozapine
DB00907 Cocaine
DB00785 Cryptenamine
DB00434 Cyproheptadine
DB00496 Darifenacin
DB01151 Desipramine
DB00804 Dicyclomine
DB08801 Dimetindene
DB01075 Diphenhydramine
DB01231 Diphenidol
DB00280 Disopyramide
DB01135 Doxacurium chloride
DB01142 Doxepin
DB00392 Ethopropazine
DB06702 Fesoterodine
DB01148 Flavoxate
DB00483 Gallamine Triethiodide
DB00986 Glycopyrronium
DB00725 Homatropine Methylbromide
DB00424 Hyoscyamine
DB00458 Imipramine
DB00332 Ipratropium bromide
DB01221 Ketamine
DB00408 Loxapine
DB00934 Maprotiline
DB01403 Methotrimeprazine
DB00462 Methylscopolamine bromide
DB00340 Metixene
DB01336 Metocurine
DB01226 Mivacurium
DB00622 Nicardipine
DB00540 Nortriptyline
DB00334 Olanzapine
DB01062 Oxybutynin
DB00383 Oxyphencyclimine
DB01337 Pancuronium
DB00715 Paroxetine
DB00454 Pethidine
DB01085 Pilocarpine
DB01338 Pipecuronium
DB00387 Procyclidine
DB00420 Promazine
DB01069 Promethazine
DB00777 Propiomazine
DB01224 Quetiapine
DB00728 Rocuronium
DB00747 Scopolamine
DB01591 Solifenacin
DB00202 Succinylcholine
DB00342 Terfenadine
DB01409 Tiotropium
DB01036 Tolterodine
DB00505 Tridihexethyl
DB00508 Triflupromazine
DB00376 Trihexyphenidyl
DB00726 Trimipramine
DB00809 Tropicamide
DB09076 Umeclidinium
DB00246 Ziprasidone
GuidetoPHARMACOLOGYi14

Protein family/group databases

GPCRDBiSearch...

PTM databases

iPTMnetiP08172
PhosphoSitePlusiP08172
SwissPalmiP08172

Polymorphism and mutation databases

BioMutaiCHRM2
DMDMi113122

Proteomic databases

PaxDbiP08172
PeptideAtlasiP08172
PRIDEiP08172
ProteomicsDBi52076

Protocols and materials databases

DNASUi1129
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000320658; ENSP00000319984; ENSG00000181072
ENST00000401861; ENSP00000384401; ENSG00000181072
ENST00000445907; ENSP00000399745; ENSG00000181072
ENST00000453373; ENSP00000415386; ENSG00000181072
GeneIDi1129
KEGGihsa:1129
UCSCiuc003vtg.2 human

Organism-specific databases

CTDi1129
DisGeNETi1129
EuPathDBiHostDB:ENSG00000181072.11
GeneCardsiCHRM2
HGNCiHGNC:1951 CHRM2
HPAiCAB022338
HPA029795
MIMi103780 phenotype
118493 gene
608516 phenotype
neXtProtiNX_P08172
OpenTargetsiENSG00000181072
PharmGKBiPA111
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG4220 Eukaryota
ENOG410YCQR LUCA
GeneTreeiENSGT00780000121874
HOGENOMiHOG000231484
HOVERGENiHBG105720
InParanoidiP08172
KOiK04130
OMAiCIKIVTK
OrthoDBiEOG091G06VI
PhylomeDBiP08172
TreeFamiTF320495

Enzyme and pathway databases

ReactomeiR-HSA-390648 Muscarinic acetylcholine receptors
R-HSA-418594 G alpha (i) signalling events
R-HSA-8856825 Cargo recognition for clathrin-mediated endocytosis
R-HSA-8856828 Clathrin-mediated endocytosis
SignaLinkiP08172
SIGNORiP08172

Miscellaneous databases

ChiTaRSiCHRM2 human
GeneWikiiMuscarinic_acetylcholine_receptor_M2
GenomeRNAii1129
PROiPR:P08172
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000181072 Expressed in 60 organ(s), highest expression level in heart
CleanExiHS_CHRM2
ExpressionAtlasiP08172 baseline and differential
GenevisibleiP08172 HS

Family and domain databases

CDDicd15297 7tmA_mAChR_M2, 1 hit
InterProiView protein in InterPro
IPR000276 GPCR_Rhodpsn
IPR017452 GPCR_Rhodpsn_7TM
IPR001065 Musac_Ach_M2_rcpt
IPR000995 Musac_Ach_rcpt
PfamiView protein in Pfam
PF00001 7tm_1, 1 hit
PRINTSiPR00237 GPCRRHODOPSN
PR00243 MUSCARINICR
PR00539 MUSCRINICM2R
SMARTiView protein in SMART
SM01381 7TM_GPCR_Srsx, 1 hit
PROSITEiView protein in PROSITE
PS00237 G_PROTEIN_RECEP_F1_1, 1 hit
PS50262 G_PROTEIN_RECEP_F1_2, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiACM2_HUMAN
AccessioniPrimary (citable) accession number: P08172
Secondary accession number(s): Q4VBK6, Q9P1X9
Entry historyiIntegrated into UniProtKB/Swiss-Prot: August 1, 1988
Last sequence update: August 1, 1988
Last modified: November 7, 2018
This is version 188 of the entry and version 1 of the sequence. See 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. SIMILARITY comments
    Index of protein domains and families
  2. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  3. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  4. Human chromosome 7
    Human chromosome 7: entries, gene names and cross-references to MIM
  5. 7-transmembrane G-linked receptors
    List of 7-transmembrane G-linked receptor entries
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