P20309 (ACM3_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Muscarinic acetylcholine receptor M3

Gene names

Name:

CHRM3

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	590 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 Pi turnover.
Subcellular location	Cell membrane; Multi-pass membrane protein. Cell junction › synapse › postsynaptic 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 component	Cell junction Cell membrane Membrane Postsynaptic cell membrane Synapse
Coding sequence diversity	Polymorphism
Domain	Transmembrane Transmembrane helix
Molecular function	G-protein coupled receptor Receptor Transducer
PTM	Disulfide bond Glycoprotein
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	cell proliferation Traceable author statement PubMed 8063729. Source: ProtInc cellular protein modification process Traceable author statement PubMed 10051746. Source: ProtInc digestion Inferred from electronic annotation. Source: Compara 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: Compara regulation of insulin secretion Traceable author statement. Source: Reactome regulation of vascular smooth muscle contraction Inferred from electronic annotation. Source: Compara small molecule metabolic process Traceable author statement. Source: Reactome smooth muscle contraction Inferred from electronic annotation. Source: Compara
Cellular_component	asymmetric synapse Inferred from electronic annotation. Source: Compara axon terminus Inferred from electronic annotation. Source: Compara 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: Compara 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 9547368. Source: ProtInc acetylcholine binding Inferred from electronic annotation. Source: Compara drug binding Inferred from electronic annotation. Source: Compara phosphatidylinositol phospholipase C activity Traceable author statement PubMed 1905013. Source: ProtInc
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 590

590

Muscarinic acetylcholine receptor M3

PRO_0000069029

Regions

Topological domain

1 – 67

67

Extracellular By similarity

Transmembrane

68 – 91

24

Helical; Name=1; By similarity

Topological domain

92 – 104

13

Cytoplasmic By similarity

Transmembrane

105 – 125

21

Helical; Name=2; By similarity

Topological domain

126 – 142

17

Extracellular By similarity

Transmembrane

143 – 164

22

Helical; Name=3; By similarity

Topological domain

165 – 184

20

Cytoplasmic By similarity

Transmembrane

185 – 207

23

Helical; Name=4; By similarity

Topological domain

208 – 229

22

Extracellular By similarity

Transmembrane

230 – 252

23

Helical; Name=5; By similarity

Topological domain

253 – 492

240

Cytoplasmic By similarity

Transmembrane

493 – 513

21

Helical; Name=6; By similarity

Topological domain

514 – 527

14

Extracellular By similarity

Transmembrane

528 – 547

20

Helical; Name=7; By similarity

Topological domain

548 – 590

43

Cytoplasmic By similarity

Motif

275 – 281

7

Basolateral sorting signal

Amino acid modifications

Glycosylation

5

1

N-linked (GlcNAc...) Potential

Glycosylation

6

1

N-linked (GlcNAc...) Potential

Glycosylation

15

1

N-linked (GlcNAc...) Potential

Glycosylation

41

1

N-linked (GlcNAc...) Potential

Glycosylation

48

1

N-linked (GlcNAc...) Potential

Disulfide bond

141 ↔ 221

By similarity

Natural variations

Natural variant

65

1

V → I.
Corresponds to variant rs2067481 [ dbSNP | Ensembl ].

VAR_033461

Natural variant

431

1

L → P.
Corresponds to variant rs16839102 [ dbSNP | Ensembl ].

VAR_049368

Experimental info

Mutagenesis

276

1

E → A: Loss of basolateral sorting. Ref.9

Mutagenesis

276

1

E → D: Loss of basolateral sorting. No effect on basolateral sorting; when associated with L-280 and L-281. Ref.9

Mutagenesis

280

1

F → A: Loss of basolateral sorting. Ref.9

Mutagenesis

280

1

F → L: No effect on basolateral sorting. Ref.9

Mutagenesis

281

1

V → A: Loss of basolateral sorting. Ref.9

Mutagenesis

281

1

V → L: No effect on basolateral sorting. Ref.9

Sequence conflict

382 – 384

3

KLP → RLS in AAG30036. Ref.7

Secondary structure

1

.

.

.

590

Helix Strand Turn

Details...

Beta strand

280 – 283

4

Sequences

	Sequence		Length	Mass (Da)
	P20309 [UniParc]. Last modified February 1, 1991. Version 1. Checksum: 5CB473C57B9526E9	FASTA	590	66,128
	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

References

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

IPI

IPI00023456.

PIR

S10128.

RefSeq

NP_000731.1. NM_000740.2.

UniGene

Hs.7138.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2CSA	NMR	-	A	271-289	[»]

ProteinModelPortal

P20309.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-44291N.

IntAct

P20309. 1 interaction.

MINT

MINT-4953628.

STRING

9606.ENSP00000255380.

Protein family/group databases

GPCRDB

Search...

PTM databases

PhosphoSite

P20309.

Polymorphism databases

DMDM

113125.

Proteomic databases

PaxDb

P20309.

PRIDE

P20309.

Protocols and materials databases

DNASU

1131.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000255380; ENSP00000255380; ENSG00000133019.

GeneID

1131.

KEGG

hsa:1131.

UCSC

uc001hyp.3. human.

Organism-specific databases

CTD

1131.

GeneCards

GC01P239549.

HGNC

HGNC:1952. CHRM3.

HPA

CAB010409.
HPA024106.

MIM

100100. phenotype.
118494. gene.

neXtProt

NX_P20309.

Orphanet

2970. Prune belly syndrome.

PharmGKB

PA112.

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG250863.

HOGENOM

HOG000231484.

HOVERGEN

HBG105720.

InParanoid

P20309.

KO

K04131.

OMA

IWQVVFI.

OrthoDB

EOG4NVZK1.

PhylomeDB

P20309.

Enzyme and pathway databases

Reactome

REACT_111102. Signal Transduction.
REACT_111217. Metabolism.

Gene expression databases

ArrayExpress

P20309.

Bgee

P20309.

CleanEx

HS_CHRM3.

Genevestigator

P20309.

GermOnline

ENSG00000133019. Homo sapiens.

Family and domain databases

InterPro

IPR000276. GPCR_Rhodpsn.
IPR017452. GPCR_Rhodpsn_7TM.
IPR001183. Musac_M3_rcpt.
IPR000995. Musac_rcpt.
[Graphical view]

Pfam

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

PRINTS

PR00237. GPCRRHODOPSN.
PR00243. MUSCARINICR.
PR00540. MUSCRINICM3R.

PROSITE

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

ProtoNet

Search...

Other

BindingDB

P20309.

ChEMBL

CHEMBL245.

ChiTaRS

CHRM3. human.

DrugBank

DB00517. 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.

EvolutionaryTrace

P20309.

GenomeRNAi

1131.

NextBio

4702.

SOURCE

Search...

Entry information

Entry name

ACM3_HUMAN

Accession

Primary (citable) accession number: P20309
Secondary accession number(s): Q0VAJ8 , Q4QRI3, Q5VXY2, Q9HB60

Entry history

Integrated into UniProtKB/Swiss-Prot:	February 1, 1991
Last sequence update:	February 1, 1991
Last modified:	May 1, 2013
This is version 137 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.