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P20309 (ACM3_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 147. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (7) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Muscarinic acetylcholine receptor M3
Gene names
Name:CHRM3
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length590 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 Pi turnover.

Subcellular location

Cell membrane; Multi-pass membrane protein. Cell junctionsynapsepostsynaptic cell membrane; Multi-pass membrane protein. Basolateral cell membrane; Multi-pass membrane protein Ref.9.

Involvement in disease

Eagle-Barrett syndrome (EGBRS) [MIM:100100]: A syndrome characterized by thin abdominal musculature with overlying lax skin, cryptorchism, megacystis with disorganized detrusor muscle, and urinary tract abnormalities.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.8

Sequence similarities

Belongs to the G-protein coupled receptor 1 family. Muscarinic acetylcholine receptor subfamily. CHRM3 sub-subfamily.

Ontologies

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

Traceable author statement PubMed 9603968. Source: ProtInc

cell proliferation

Traceable author statement PubMed 8063729. Source: ProtInc

cellular protein modification process

Traceable author statement PubMed 10051746. Source: ProtInc

energy reserve metabolic process

Traceable author statement. Source: Reactome

nervous system development

Traceable author statement PubMed 2739737. Source: ProtInc

positive regulation of smooth muscle contraction

Inferred from electronic annotation. Source: Ensembl

regulation of insulin secretion

Traceable author statement. Source: Reactome

regulation of vascular smooth muscle contraction

Inferred from electronic annotation. Source: Ensembl

saliva secretion

Inferred from electronic annotation. Source: InterPro

signal transduction

Traceable author statement PubMed 10940357. Source: ProtInc

small molecule metabolic process

Traceable author statement. Source: Reactome

smooth muscle contraction

Inferred from electronic annotation. Source: Ensembl

   Cellular_componentasymmetric synapse

Inferred from electronic annotation. Source: Ensembl

axon terminus

Inferred from electronic annotation. Source: Ensembl

basolateral plasma membrane

Inferred from electronic annotation. Source: UniProtKB-SubCell

cell junction

Inferred from electronic annotation. Source: UniProtKB-KW

dendrite

Inferred from electronic annotation. Source: Ensembl

integral component of plasma membrane

Traceable author statement Ref.1. Source: ProtInc

plasma membrane

Traceable author statement. Source: Reactome

postsynaptic membrane

Inferred from electronic annotation. Source: UniProtKB-SubCell

   Molecular_functionG-protein coupled acetylcholine receptor activity

Traceable author statement PubMed 9547368. Source: ProtInc

acetylcholine binding

Inferred from electronic annotation. Source: Ensembl

drug binding

Inferred from electronic annotation. Source: Ensembl

phosphatidylinositol phospholipase C activity

Traceable author statement PubMed 1905013. Source: ProtInc

receptor activity

Traceable author statement PubMed 10940357. Source: ProtInc

Complete GO annotation...

Binary interactions

With

Entry

#Exp.

IntAct

Notes

NALCNQ8IZF03EBI-2687785,EBI-7085333

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 590590Muscarinic acetylcholine receptor M3
PRO_0000069029

Regions

Topological domain1 – 6767Extracellular By similarity
Transmembrane68 – 9124Helical; Name=1; By similarity
Topological domain92 – 10413Cytoplasmic By similarity
Transmembrane105 – 12521Helical; Name=2; By similarity
Topological domain126 – 14217Extracellular By similarity
Transmembrane143 – 16422Helical; Name=3; By similarity
Topological domain165 – 18420Cytoplasmic By similarity
Transmembrane185 – 20723Helical; Name=4; By similarity
Topological domain208 – 22922Extracellular By similarity
Transmembrane230 – 25223Helical; Name=5; By similarity
Topological domain253 – 492240Cytoplasmic By similarity
Transmembrane493 – 51321Helical; Name=6; By similarity
Topological domain514 – 52714Extracellular By similarity
Transmembrane528 – 54720Helical; Name=7; By similarity
Topological domain548 – 59043Cytoplasmic By similarity
Motif275 – 2817Basolateral sorting signal

Amino acid modifications

Glycosylation51N-linked (GlcNAc...) Potential
Glycosylation61N-linked (GlcNAc...) Potential
Glycosylation151N-linked (GlcNAc...) Potential
Glycosylation411N-linked (GlcNAc...) Potential
Glycosylation481N-linked (GlcNAc...) Potential
Disulfide bond141 ↔ 221 By similarity

Natural variations

Natural variant651V → I.
Corresponds to variant rs2067481 [ dbSNP | Ensembl ].
VAR_033461
Natural variant4311L → P.
Corresponds to variant rs16839102 [ dbSNP | Ensembl ].
VAR_049368

Experimental info

Mutagenesis2761E → A: Loss of basolateral sorting. Ref.9
Mutagenesis2761E → D: Loss of basolateral sorting. No effect on basolateral sorting; when associated with L-280 and L-281. Ref.9
Mutagenesis2801F → A: Loss of basolateral sorting. Ref.9
Mutagenesis2801F → L: No effect on basolateral sorting. Ref.9
Mutagenesis2811V → A: Loss of basolateral sorting. Ref.9
Mutagenesis2811V → L: No effect on basolateral sorting. Ref.9
Sequence conflict382 – 3843KLP → RLS in AAG30036. Ref.7

Secondary structure

... 590
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
P20309 [UniParc].

Last modified February 1, 1991. Version 1.
Checksum: 5CB473C57B9526E9

FASTA59066,128
        10         20         30         40         50         60 
MTLHNNSTTS PLFPNISSSW IHSPSDAGLP PGTVTHFGSY NVSRAAGNFS SPDGTTDDPL 

        70         80         90        100        110        120 
GGHTVWQVVF IAFLTGILAL VTIIGNILVI VSFKVNKQLK TVNNYFLLSL ACADLIIGVI 

       130        140        150        160        170        180 
SMNLFTTYII MNRWALGNLA CDLWLAIDYV ASNASVMNLL VISFDRYFSI TRPLTYRAKR 

       190        200        210        220        230        240 
TTKRAGVMIG LAWVISFVLW APAILFWQYF VGKRTVPPGE CFIQFLSEPT ITFGTAIAAF 

       250        260        270        280        290        300 
YMPVTIMTIL YWRIYKETEK RTKELAGLQA SGTEAETENF VHPTGSSRSC SSYELQQQSM 

       310        320        330        340        350        360 
KRSNRRKYGR CHFWFTTKSW KPSSEQMDQD HSSSDSWNNN DAAASLENSA SSDEEDIGSE 

       370        380        390        400        410        420 
TRAIYSIVLK LPGHSTILNS TKLPSSDNLQ VPEEELGMVD LERKADKLQA QKSVDDGGSF 

       430        440        450        460        470        480 
PKSFSKLPIQ LESAVDTAKT SDVNSSVGKS TATLPLSFKE ATLAKRFALK TRSQITKRKR 

       490        500        510        520        530        540 
MSLVKEKKAA QTLSAILLAF IITWTPYNIM VLVNTFCDSC IPKTFWNLGY WLCYINSTVN 

       550        560        570        580        590 
PVCYALCNKT FRTTFKMLLL CQCDKKKRRK QQYQQRQSVI FHKRAPEQAL 

« Hide

References

« Hide 'large scale' references
[1]"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].
[2]"Cloning and expression of the human and rat m5 muscarinic acetylcholine receptor genes."
Bonner T.I., Young A.C., Brann M.R., Buckley N.J.
Neuron 1:403-410(1988) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[3]"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].
[4]"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.
[5]"The DNA sequence and biological annotation of human chromosome 1."
Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A., Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C., Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K. expand/collapse author list , Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C., Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W., Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J., Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H., Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L., Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J., Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S., Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K., Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R., Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M., Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S., Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J., Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N., Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V., Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J., Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E., Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S., Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M., White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H., Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E., Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G., Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.
Nature 441:315-321(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]"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].
[7]"Antisense promoter of human L1 retrotransposon drives transcription of adjacent cellular genes."
Speek M.
Mol. Cell. Biol. 21:1973-1985(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 1-384.
Tissue: Teratocarcinoma.
[8]"Muscarinic acetylcholine receptor M3 mutation causes urinary bladder disease and a prune-belly-like syndrome."
Weber S., Thiele H., Mir S., Toliat M.R., Sozeri B., Reutter H., Draaken M., Ludwig M., Altmuller J., Frommolt P., Stuart H.M., Ranjzad P., Hanley N.A., Jennings R., Newman W.G., Wilcox D.T., Thiel U., Schlingmann K.P. expand/collapse author list , Beetz R., Hoyer P.F., Konrad M., Schaefer F., Nurnberg P., Woolf A.S.
Am. J. Hum. Genet. 89:668-674(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: INVOLVEMENT IN EGBRS.
[9]"Identification and structural determination of the M(3) muscarinic acetylcholine receptor basolateral sorting signal."
Iverson H.A., Fox D. III, Nadler L.S., Klevit R.E., Nathanson N.M.
J. Biol. Chem. 280:24568-24575(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: STRUCTURE BY NMR OF 271-289, MUTAGENESIS OF GLU-276; PHE-280 AND VAL-281, SUBCELLULAR LOCATION.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
X15266 Genomic DNA. Translation: CAA33337.1.
U29589 Genomic DNA. Translation: AAA70337.1.
AB041395 Genomic DNA. Translation: BAA94480.1.
AF498917 mRNA. Translation: AAM18940.1.
AL356361 Genomic DNA. Translation: CAH72987.1.
BC096844 mRNA. Translation: AAH96844.1.
BC121026 mRNA. Translation: AAI21027.1.
AF279779 mRNA. Translation: AAG30036.1.
PIRS10128.
RefSeqNP_000731.1. NM_000740.2.
XP_005273089.1. XM_005273032.1.
XP_005273090.1. XM_005273033.1.
XP_005273091.1. XM_005273034.1.
UniGeneHs.155736.
Hs.7138.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
2CSANMR-A271-289[»]
ProteinModelPortalP20309.
SMRP20309. Positions 64-560.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid107553. 4 interactions.
DIPDIP-44291N.
IntActP20309. 3 interactions.
MINTMINT-4953628.
STRING9606.ENSP00000255380.

Chemistry

BindingDBP20309.
ChEMBLCHEMBL245.
DrugBankDB00517. Anisotropine Methylbromide.
DB00572. Atropine.
DB00767. Benzquinamide.
DB00185. Cevimeline.
DB00785. Cryptenamine.
DB01176. Cyclizine.
DB00496. Darifenacin.
DB00729. Diphemanil Methylsulfate.
DB01231. Diphenidol.
DB00725. Homatropine Methylbromide.
DB01403. Methotrimeprazine.
DB00340. Metixene.
DB00334. Olanzapine.
DB01062. Oxybutynin.
DB00383. Oxyphencyclimine.
DB00420. Promazine.
DB01069. Promethazine.
DB00777. Propiomazine.
DB01591. Solifenacin.
DB00372. Thiethylperazine.
DB01409. Tiotropium.
DB01036. Tolterodine.
DB00505. Tridihexethyl.
GuidetoPHARMACOLOGY15.

Protein family/group databases

GPCRDBSearch...

PTM databases

PhosphoSiteP20309.

Polymorphism databases

DMDM113125.

Proteomic databases

PaxDbP20309.
PRIDEP20309.

Protocols and materials databases

DNASU1131.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000255380; ENSP00000255380; ENSG00000133019.
GeneID1131.
KEGGhsa:1131.
UCSCuc001hyp.3. human.

Organism-specific databases

CTD1131.
GeneCardsGC01P239549.
HGNCHGNC:1952. CHRM3.
HPACAB010409.
HPA024106.
MIM100100. phenotype.
118494. gene.
neXtProtNX_P20309.
Orphanet2970. Prune belly syndrome.
PharmGKBPA112.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG250863.
HOGENOMHOG000231484.
HOVERGENHBG105720.
InParanoidP20309.
KOK04131.
OMAIWQVVFI.
OrthoDBEOG7V49Z7.
PhylomeDBP20309.
TreeFamTF320495.

Enzyme and pathway databases

ReactomeREACT_111102. Signal Transduction.
REACT_111217. Metabolism.
SignaLinkP20309.

Gene expression databases

ArrayExpressP20309.
BgeeP20309.
CleanExHS_CHRM3.
GenevestigatorP20309.

Family and domain databases

Gene3D1.20.1070.10. 2 hits.
InterProIPR000276. GPCR_Rhodpsn.
IPR017452. GPCR_Rhodpsn_7TM.
IPR001183. Musac_Ach_M3_rcpt.
IPR000995. Musac_Ach_rcpt.
[Graphical view]
PANTHERPTHR24249:SF61. PTHR24249:SF61. 1 hit.
PfamPF00001. 7tm_1. 1 hit.
[Graphical view]
PRINTSPR00237. GPCRRHODOPSN.
PR00243. MUSCARINICR.
PR00540. MUSCRINICM3R.
PROSITEPS00237. G_PROTEIN_RECEP_F1_1. 1 hit.
PS50262. G_PROTEIN_RECEP_F1_2. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSCHRM3. human.
EvolutionaryTraceP20309.
GeneWikiMuscarinic_acetylcholine_receptor_M3.
GenomeRNAi1131.
NextBio4702.
PROP20309.
SOURCESearch...

Entry information

Entry nameACM3_HUMAN
AccessionPrimary (citable) accession number: P20309
Secondary accession number(s): Q0VAJ8 expand/collapse secondary AC list , Q4QRI3, Q5VXY2, Q9HB60
Entry history
Integrated into UniProtKB/Swiss-Prot: February 1, 1991
Last sequence update: February 1, 1991
Last modified: April 16, 2014
This is version 147 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 polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 1

Human chromosome 1: entries, gene names and cross-references to MIM

7-transmembrane G-linked receptors

List of 7-transmembrane G-linked receptor entries