P08483 (ACM3_RAT) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Muscarinic acetylcholine receptor M3

Gene names

Name:	Chrm3
Synonyms:	Chrm-3

Organism

Rattus norvegicus (Rat)

Taxonomic identifier

10116 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Rattus

Protein attributes

Sequence length	589 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 By similarity. Cell junction › synapse › postsynaptic cell membrane; Multi-pass membrane protein By similarity. Basolateral cell membrane; Multi-pass membrane protein By similarity.
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
Domain	Transmembrane Transmembrane helix
Molecular function	G-protein coupled receptor Receptor Transducer
PTM	Disulfide bond Glycoprotein Phosphoprotein
Technical term	3D-structure Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological process	positive regulation of smooth muscle contraction Inferred from mutant phenotype. Source: RGD regulation of vascular smooth muscle contraction Inferred from mutant phenotype. Source: RGD
Cellular component	asymmetric synapse Inferred from direct assay. Source: RGD axon terminus Inferred from direct assay. Source: RGD basolateral plasma membrane Inferred from electronic annotation. Source: UniProtKB-SubCell cell junction Inferred from electronic annotation. Source: UniProtKB-KW dendrite Inferred from direct assay. Source: RGD integral to membrane Inferred from electronic annotation. Source: UniProtKB-KW postsynaptic membrane Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular function	G-protein coupled acetylcholine receptor activity Inferred from direct assay. Source: RGD acetylcholine binding Inferred from mutant phenotype. Source: RGD drug binding Inferred from direct assay. Source: RGD
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 589	589	Muscarinic acetylcholine receptor M3		PRO_0000069034
Regions
	Topological domain	1 – 66	66	Extracellular By similarity
	Transmembrane	67 – 90	24	Helical; Name=1; By similarity
	Topological domain	91 – 103	13	Cytoplasmic By similarity
	Transmembrane	104 – 124	21	Helical; Name=2; By similarity
	Topological domain	125 – 141	17	Extracellular By similarity
	Transmembrane	142 – 163	22	Helical; Name=3; By similarity
	Topological domain	164 – 183	20	Cytoplasmic By similarity
	Transmembrane	184 – 206	23	Helical; Name=4; By similarity
	Topological domain	207 – 228	22	Extracellular By similarity
	Transmembrane	229 – 251	23	Helical; Name=5; By similarity
	Topological domain	252 – 491	240	Cytoplasmic By similarity
	Transmembrane	492 – 512	21	Helical; Name=6; By similarity
	Topological domain	513 – 526	14	Extracellular By similarity
	Transmembrane	527 – 546	20	Helical; Name=7; By similarity
	Topological domain	547 – 589	43	Cytoplasmic By similarity
	Motif	274 – 280	7	Basolateral sorting signal By similarity
Sites
	Binding site	147	1	Antagonist By similarity
Amino acid modifications
	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
	Glycosylation	52	1	N-linked (GlcNAc...) Potential
	Disulfide bond	140 ↔ 220		By similarity
Experimental info
	Mutagenesis	148	1	Y → A: Decreased affinity for acetylcholine. Ref.6
	Mutagenesis	231	1	T → A: Decreased affinity for acetylcholine. Ref.6
	Mutagenesis	234	1	T → A: Strongly decreased affinity for acetylcholine. Ref.6 Ref.7
	Mutagenesis	506	1	Y → F: Decreased affinity for acetylcholine. Ref.6 Ref.7
	Mutagenesis	529	1	Y → F: Decreased affinity for acetylcholine. Ref.6
	Mutagenesis	533	1	Y → F: Decreased affinity for acetylcholine. Ref.6
	Sequence conflict	184	1	A → R in AAA40661. Ref.1
	Sequence conflict	184	1	A → R in AAA40662. Ref.1
	Sequence conflict	184	1	A → R in BAA36839. Ref.4
	Sequence conflict	516	1	C → R in AAA40659. Ref.3
	Sequence conflict	556	1	T → M in AAA40659. Ref.3

Sequences

	Sequence		Length	Mass (Da)
	P08483 [UniParc]. Last modified November 1, 1988. Version 1. Checksum: 9A5EF2FA653C830A	FASTA	589	66,066
	10 20 30 40 50 60 MTLHSNSTTS PLFPNISSSW VHSPSEAGLP LGTVTQLGSY NISQETGNFS SNDTSSDPLG 70 80 90 100 110 120 GHTIWQVVFI AFLTGFLALV TIIGNILVIV AFKVNKQLKT VNNYFLLSLA CADLIIGVIS 130 140 150 160 170 180 MNLFTTYIIM NRWALGNLAC DLWLSIDYVA SNASVMNLLV ISFDRYFSIT RPLTYRAKRT 190 200 210 220 230 240 TKRAGVMIGL AWVISFVLWA PAILFWQYFV GKRTVPPGEC FIQFLSEPTI TFGTAIAAFY 250 260 270 280 290 300 MPVTIMTILY WRIYKETEKR TKELAGLQAS GTEAEAENFV HPTGSSRSCS SYELQQQGVK 310 320 330 340 350 360 RSSRRKYGRC HFWFTTKSWK PSAEQMDQDH SSSDSWNNND AAASLENSAS SDEEDIGSET 370 380 390 400 410 420 RAIYSIVLKL PGHSSILNST KLPSSDNLQV SNEDLGTVDV ERNAHKLQAQ KSMGDGDNCQ 430 440 450 460 470 480 KDFTKLPIQL ESAVDTGKTS DTNSSADKTT ATLPLSFKEA TLAKRFALKT RSQITKRKRM 490 500 510 520 530 540 SLIKEKKAAQ TLSAILLAFI ITWTPYNIMV LVNTFCDSCI PKTYWNLGYW LCYINSTVNP 550 560 570 580 VCYALCNKTF RTTFKTLLLC QCDKRKRRKQ QYQQRQSVIF HKRVPEQAL

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: 3037705] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA].
[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: 3272174] [Abstract] Cited for: SEQUENCE REVISION TO 184.
[3]	"A novel subtype of muscarinic receptor identified by homology screening." Braun T., Schofield P.R., Shivers B.D., Pritchett D.B., Seeburg P.H. Biochem. Biophys. Res. Commun. 149:125-132(1987) [PubMed: 3120722] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Brain.
[4]	"Molecular cloning of m3 muscarinic acetylcholine receptor in rat iris." Furuta M., Ohya S., Imaizumi Y., Watanabe M. J. Smooth Muscle Res. 34:111-122(1998) [PubMed: 9972520] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Iris.
[5]	"Muscarinic acetylcholine receptors. Peptide sequencing identifies residues involved in antagonist binding and disulfide bond formation." Kurtenbach E., Curtis C.A.M., Pedder E.K., Aitken A., Harris A.C.M., Hulme E.C. J. Biol. Chem. 265:13702-13708(1990) [PubMed: 2380182] [Abstract] Cited for: PROTEIN SEQUENCE OF 104-166.
[6]	"Site-directed mutagenesis of the m3 muscarinic receptor: identification of a series of threonine and tyrosine residues involved in agonist but not antagonist binding." Wess J., Gdula D., Brann M.R. EMBO J. 10:3729-3734(1991) [PubMed: 1657592] [Abstract] Cited for: MUTAGENESIS OF TYR-148; THR-231; THR-234; TYR-506; TYR-529 AND TYR-533.
[7]	"Role of conserved threonine and tyrosine residues in acetylcholine binding and muscarinic receptor activation. A study with m3 muscarinic receptor point mutants." Wess J., Maggio R., Palmer J.R., Vogel Z. J. Biol. Chem. 267:19313-19319(1992) [PubMed: 1527051] [Abstract] Cited for: MUTAGENESIS OF THR-234 AND TYR-506.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

M16407 mRNA. Translation: AAA40661.1. Sequence problems.
M16408 Genomic DNA. Translation: AAA40662.1. Sequence problems.
M18088 mRNA. Translation: AAA40659.1.
M62826 Genomic DNA. Translation: AAA41553.1.
AB017656 mRNA. Translation: BAA36839.1.

IPI

IPI00327521.

PIR

A29476.
B29514. B94518.

RefSeq

NP_036659.1. NM_012527.1.

UniGene

Rn.87735.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2AMK	model	-	A	56-560	[»]

ProteinModelPortal

P08483.

ModBase

Search...

Protein-protein interaction databases

STRING

P08483.

Protein family/group databases

GPCRDB

Search...

PTM databases

PhosphoSite

P08483.

Proteomic databases

PRIDE

P08483.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENSRNOT00000019662; ENSRNOP00000019662; ENSRNOG00000014639.

GeneID

24260.

KEGG

rno:24260.

UCSC

NM_012527. rat.

Organism-specific databases

CTD

1131.

RGD

2343. Chrm3.

Phylogenomic databases

eggNOG

maNOG13832.

GeneTree

ENSGT00560000076730.

HOVERGEN

HBG105720.

InParanoid

P08483.

OMA

IWQVVFI.

OrthoDB

EOG4NVZK1.

PhylomeDB

P08483.

Gene expression databases

ArrayExpress

P08483.

Genevestigator

P08483.

GermOnline

ENSRNOG00000014639. Rattus norvegicus.

Family and domain databases

InterPro

IPR000276. 7TM_GPCR_Rhodpsn.
IPR017452. GPCR_Rhodpsn_supfam.
IPR001183. Musac_M3_rcpt.
IPR000995. Musac_rcpt.
[Graphical view]

KO

K04131.

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

NextBio

602805.

Entry information

Entry name

ACM3_RAT

Accession

Primary (citable) accession number: P08483
Secondary accession number(s): Q9QWK9

Entry history

Integrated into UniProtKB/Swiss-Prot:	August 1, 1988
Last sequence update:	November 1, 1988
Last modified:	January 25, 2012
This is version 107 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program