ACM3_RAT
ID ACM3_RAT Reviewed; 589 AA.
AC P08483; Q9QWK9;
DT 01-AUG-1988, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1988, sequence version 1.
DT 03-AUG-2022, entry version 186.
DE RecName: Full=Muscarinic acetylcholine receptor M3;
GN Name=Chrm3; Synonyms=Chrm-3;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA].
RX PubMed=3037705; DOI=10.1126/science.3037705;
RA Bonner T.I., Buckley N.J., Young A.C., Brann M.R.;
RT "Identification of a family of muscarinic acetylcholine receptor genes.";
RL Science 237:527-532(1987).
RN [2]
RP SEQUENCE REVISION TO 184.
RX PubMed=3272174; DOI=10.1016/0896-6273(88)90190-0;
RA Bonner T.I., Young A.C., Brann M.R., Buckley N.J.;
RT "Cloning and expression of the human and rat m5 muscarinic acetylcholine
RT receptor genes.";
RL Neuron 1:403-410(1988).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Brain;
RX PubMed=3120722; DOI=10.1016/0006-291x(87)91613-5;
RA Braun T., Schofield P.R., Shivers B.D., Pritchett D.B., Seeburg P.H.;
RT "A novel subtype of muscarinic receptor identified by homology screening.";
RL Biochem. Biophys. Res. Commun. 149:125-132(1987).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Iris;
RX PubMed=9972520; DOI=10.1540/jsmr.34.111;
RA Furuta M., Ohya S., Imaizumi Y., Watanabe M.;
RT "Molecular cloning of m3 muscarinic acetylcholine receptor in rat iris.";
RL J. Smooth Muscle Res. 34:111-122(1998).
RN [5]
RP PROTEIN SEQUENCE OF 104-166.
RX PubMed=2380182; DOI=10.1016/s0021-9258(18)77406-1;
RA Kurtenbach E., Curtis C.A.M., Pedder E.K., Aitken A., Harris A.C.M.,
RA Hulme E.C.;
RT "Muscarinic acetylcholine receptors. Peptide sequencing identifies residues
RT involved in antagonist binding and disulfide bond formation.";
RL J. Biol. Chem. 265:13702-13708(1990).
RN [6]
RP MUTAGENESIS OF TYR-148; THR-231; THR-234; TYR-506; TYR-529 AND TYR-533,
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=1657592; DOI=10.1002/j.1460-2075.1991.tb04941.x;
RA Wess J., Gdula D., Brann M.R.;
RT "Site-directed mutagenesis of the m3 muscarinic receptor: identification of
RT a series of threonine and tyrosine residues involved in agonist but not
RT antagonist binding.";
RL EMBO J. 10:3729-3734(1991).
RN [7]
RP MUTAGENESIS OF THR-234 AND TYR-506, FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=1527051; DOI=10.1016/s0021-9258(18)41776-0;
RA Wess J., Maggio R., Palmer J.R., Vogel Z.;
RT "Role of conserved threonine and tyrosine residues in acetylcholine binding
RT and muscarinic receptor activation. A study with m3 muscarinic receptor
RT point mutants.";
RL J. Biol. Chem. 267:19313-19319(1992).
RN [8]
RP X-RAY CRYSTALLOGRAPHY (3.40 ANGSTROMS) OF 57-589 IN COMPLEX WITH THE
RP INVERSE AGONIST TIOTROPIUM, FUNCTION, SUBCELLULAR LOCATION, TOPOLOGY, AND
RP DISULFIDE BOND.
RX PubMed=22358844; DOI=10.1038/nature10867;
RA Kruse A.C., Hu J., Pan A.C., Arlow D.H., Rosenbaum D.M., Rosemond E.,
RA Green H.F., Liu T., Chae P.S., Dror R.O., Shaw D.E., Weis W.I., Wess J.,
RA Kobilka B.K.;
RT "Structure and dynamics of the M3 muscarinic acetylcholine receptor.";
RL Nature 482:552-556(2012).
CC -!- FUNCTION: The muscarinic acetylcholine receptor mediates various
CC cellular responses, including inhibition of adenylate cyclase,
CC breakdown of phosphoinositides and modulation of potassium channels
CC through the action of G proteins. Primary transducing effect is Pi
CC turnover. {ECO:0000269|PubMed:1527051, ECO:0000269|PubMed:1657592,
CC ECO:0000269|PubMed:22358844}.
CC -!- SUBUNIT: Homodimer; the dimers can form tetramers (By similarity).
CC Interacts with NALCN (By similarity). Interacts with TMEM147 (By
CC similarity). {ECO:0000250|UniProtKB:P20309,
CC ECO:0000250|UniProtKB:Q9ERZ3}.
CC -!- INTERACTION:
CC P08483; P11275: Camk2a; NbExp=2; IntAct=EBI-7946407, EBI-2640645;
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:1527051};
CC Multi-pass membrane protein {ECO:0000255}. Postsynaptic cell membrane;
CC Multi-pass membrane protein {ECO:0000255}. Basolateral cell membrane
CC {ECO:0000250|UniProtKB:P20309}; Multi-pass membrane protein
CC {ECO:0000255}. Endoplasmic reticulum membrane
CC {ECO:0000250|UniProtKB:P20309}; Multi-pass membrane protein
CC {ECO:0000255}. Note=Colocalizes with TMEM147 in the endoplasmic
CC reticulum (ER) membrane. TMEM147 impairs its trafficking to the cell
CC membrane leading to its retention in the ER membrane.
CC {ECO:0000250|UniProtKB:P20309}.
CC -!- SIMILARITY: Belongs to the G-protein coupled receptor 1 family.
CC Muscarinic acetylcholine receptor subfamily. CHRM3 sub-subfamily.
CC {ECO:0000255|PROSITE-ProRule:PRU00521}.
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DR EMBL; M16407; AAA40661.1; -; mRNA.
DR EMBL; M16408; AAA40662.1; -; Genomic_DNA.
DR EMBL; M18088; AAA40659.1; -; mRNA.
DR EMBL; M62826; AAA41553.1; -; Genomic_DNA.
DR EMBL; AB017656; BAA36839.1; -; mRNA.
DR PIR; A29476; A29476.
DR PIR; B94518; B29514.
DR RefSeq; NP_036659.2; NM_012527.2.
DR RefSeq; XP_017455938.1; XM_017600449.1.
DR RefSeq; XP_017455939.1; XM_017600450.1.
DR RefSeq; XP_017455940.1; XM_017600451.1.
DR RefSeq; XP_017455941.1; XM_017600452.1.
DR PDB; 4DAJ; X-ray; 3.40 A; A/B/C/D=57-259, A/B/C/D=482-589.
DR PDB; 4U14; X-ray; 3.57 A; A=57-259, A=482-563.
DR PDB; 4U15; X-ray; 2.80 A; A/B=57-259, A/B=482-563.
DR PDB; 4U16; X-ray; 3.70 A; A/B=57-259, A/B=482-563.
DR PDB; 5ZHP; X-ray; 3.10 A; A/B=57-308, A/B=482-569.
DR PDBsum; 4DAJ; -.
DR PDBsum; 4U14; -.
DR PDBsum; 4U15; -.
DR PDBsum; 4U16; -.
DR PDBsum; 5ZHP; -.
DR AlphaFoldDB; P08483; -.
DR SMR; P08483; -.
DR IntAct; P08483; 1.
DR MINT; P08483; -.
DR STRING; 10116.ENSRNOP00000067435; -.
DR BindingDB; P08483; -.
DR ChEMBL; CHEMBL320; -.
DR DrugCentral; P08483; -.
DR GuidetoPHARMACOLOGY; 15; -.
DR GlyGen; P08483; 5 sites.
DR PhosphoSitePlus; P08483; -.
DR PaxDb; P08483; -.
DR Ensembl; ENSRNOT00000075651; ENSRNOP00000067435; ENSRNOG00000049410.
DR Ensembl; ENSRNOT00000102670; ENSRNOP00000090085; ENSRNOG00000049410.
DR Ensembl; ENSRNOT00000103154; ENSRNOP00000090433; ENSRNOG00000049410.
DR Ensembl; ENSRNOT00000107962; ENSRNOP00000086603; ENSRNOG00000049410.
DR Ensembl; ENSRNOT00000113544; ENSRNOP00000087869; ENSRNOG00000049410.
DR Ensembl; ENSRNOT00000118676; ENSRNOP00000080306; ENSRNOG00000049410.
DR GeneID; 24260; -.
DR KEGG; rno:24260; -.
DR UCSC; RGD:2343; rat.
DR CTD; 1131; -.
DR RGD; 2343; Chrm3.
DR eggNOG; KOG4220; Eukaryota.
DR GeneTree; ENSGT00940000160084; -.
DR HOGENOM; CLU_009579_11_2_1; -.
DR InParanoid; P08483; -.
DR OMA; TWACDLW; -.
DR OrthoDB; 1245472at2759; -.
DR PhylomeDB; P08483; -.
DR TreeFam; TF320495; -.
DR Reactome; R-RNO-390648; Muscarinic acetylcholine receptors.
DR Reactome; R-RNO-416476; G alpha (q) signalling events.
DR PRO; PR:P08483; -.
DR Proteomes; UP000002494; Chromosome 17.
DR Bgee; ENSRNOG00000049410; Expressed in frontal cortex and 12 other tissues.
DR Genevisible; P08483; RN.
DR GO; GO:0070161; C:anchoring junction; IEA:UniProtKB-KW.
DR GO; GO:0032279; C:asymmetric synapse; IDA:RGD.
DR GO; GO:0043679; C:axon terminus; IDA:RGD.
DR GO; GO:0009925; C:basal plasma membrane; ISO:RGD.
DR GO; GO:0016323; C:basolateral plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0030425; C:dendrite; IDA:RGD.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0098978; C:glutamatergic synapse; IDA:SynGO.
DR GO; GO:0005887; C:integral component of plasma membrane; IDA:UniProtKB.
DR GO; GO:0099061; C:integral component of postsynaptic density membrane; IDA:SynGO.
DR GO; GO:0099056; C:integral component of presynaptic membrane; IDA:SynGO.
DR GO; GO:0016020; C:membrane; IDA:RGD.
DR GO; GO:0045202; C:synapse; IBA:GO_Central.
DR GO; GO:0042166; F:acetylcholine binding; IDA:UniProtKB.
DR GO; GO:0016907; F:G protein-coupled acetylcholine receptor activity; IDA:UniProtKB.
DR GO; GO:0031789; F:G protein-coupled acetylcholine receptor binding; IDA:RGD.
DR GO; GO:0004993; F:G protein-coupled serotonin receptor activity; IBA:GO_Central.
DR GO; GO:0030594; F:neurotransmitter receptor activity; IBA:GO_Central.
DR GO; GO:0050997; F:quaternary ammonium group binding; IDA:RGD.
DR GO; GO:0095500; P:acetylcholine receptor signaling pathway; ISO:RGD.
DR GO; GO:0007197; P:adenylate cyclase-inhibiting G protein-coupled acetylcholine receptor signaling pathway; IBA:GO_Central.
DR GO; GO:0019722; P:calcium-mediated signaling; ISO:RGD.
DR GO; GO:0007268; P:chemical synaptic transmission; IBA:GO_Central.
DR GO; GO:0007213; P:G protein-coupled acetylcholine receptor signaling pathway; IDA:UniProtKB.
DR GO; GO:0007187; P:G protein-coupled receptor signaling pathway, coupled to cyclic nucleotide second messenger; IBA:GO_Central.
DR GO; GO:0003063; P:negative regulation of heart rate by acetylcholine; IMP:RGD.
DR GO; GO:0045987; P:positive regulation of smooth muscle contraction; ISO:RGD.
DR GO; GO:1904695; P:positive regulation of vascular associated smooth muscle contraction; IMP:RGD.
DR GO; GO:0045907; P:positive regulation of vasoconstriction; IMP:RGD.
DR GO; GO:0032412; P:regulation of ion transmembrane transporter activity; ISO:RGD.
DR GO; GO:0003056; P:regulation of vascular associated smooth muscle contraction; IBA:GO_Central.
DR GO; GO:1905144; P:response to acetylcholine; IMP:RGD.
DR GO; GO:0046541; P:saliva secretion; ISO:RGD.
DR GO; GO:0006939; P:smooth muscle contraction; ISO:RGD.
DR GO; GO:0007271; P:synaptic transmission, cholinergic; ISO:RGD.
DR InterPro; IPR000276; GPCR_Rhodpsn.
DR InterPro; IPR017452; GPCR_Rhodpsn_7TM.
DR InterPro; IPR001183; Musac_Ach_M3_rcpt.
DR InterPro; IPR000995; Musac_Ach_rcpt.
DR Pfam; PF00001; 7tm_1; 1.
DR PRINTS; PR00237; GPCRRHODOPSN.
DR PRINTS; PR00243; MUSCARINICR.
DR PRINTS; PR00540; MUSCRINICM3R.
DR SMART; SM01381; 7TM_GPCR_Srsx; 1.
DR PROSITE; PS00237; G_PROTEIN_RECEP_F1_1; 1.
DR PROSITE; PS50262; G_PROTEIN_RECEP_F1_2; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Cell membrane; Direct protein sequencing; Disulfide bond;
KW Endoplasmic reticulum; G-protein coupled receptor; Glycoprotein; Membrane;
KW Phosphoprotein; Postsynaptic cell membrane; Receptor; Reference proteome;
KW Synapse; Transducer; Transmembrane; Transmembrane helix.
FT CHAIN 1..589
FT /note="Muscarinic acetylcholine receptor M3"
FT /id="PRO_0000069034"
FT TOPO_DOM 1..66
FT /note="Extracellular"
FT /evidence="ECO:0000269|PubMed:22358844"
FT TRANSMEM 67..90
FT /note="Helical; Name=1"
FT TOPO_DOM 91..103
FT /note="Cytoplasmic"
FT /evidence="ECO:0000269|PubMed:22358844"
FT TRANSMEM 104..129
FT /note="Helical; Name=2"
FT TOPO_DOM 130..141
FT /note="Extracellular"
FT /evidence="ECO:0000269|PubMed:22358844"
FT TRANSMEM 142..163
FT /note="Helical; Name=3"
FT TOPO_DOM 164..183
FT /note="Cytoplasmic"
FT /evidence="ECO:0000269|PubMed:22358844"
FT TRANSMEM 184..205
FT /note="Helical; Name=4"
FT TOPO_DOM 206..228
FT /note="Extracellular"
FT /evidence="ECO:0000269|PubMed:22358844"
FT TRANSMEM 229..251
FT /note="Helical; Name=5"
FT TOPO_DOM 252..490
FT /note="Cytoplasmic"
FT /evidence="ECO:0000269|PubMed:22358844"
FT TRANSMEM 491..513
FT /note="Helical; Name=6"
FT TOPO_DOM 514..525
FT /note="Extracellular"
FT /evidence="ECO:0000269|PubMed:22358844"
FT TRANSMEM 526..545
FT /note="Helical; Name=7"
FT TOPO_DOM 546..589
FT /note="Cytoplasmic"
FT /evidence="ECO:0000269|PubMed:22358844"
FT REGION 323..356
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 274..280
FT /note="Basolateral sorting signal"
FT /evidence="ECO:0000250"
FT COMPBIAS 323..351
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 384
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9ERZ3"
FT CARBOHYD 6
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 15
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 41
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 48
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 52
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 140..220
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00521,
FT ECO:0000269|PubMed:22358844"
FT DISULFID 516..519
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00521,
FT ECO:0000269|PubMed:22358844"
FT MUTAGEN 148
FT /note="Y->A: Decreased affinity for acetylcholine."
FT /evidence="ECO:0000269|PubMed:1657592"
FT MUTAGEN 231
FT /note="T->A: Decreased affinity for acetylcholine."
FT /evidence="ECO:0000269|PubMed:1657592"
FT MUTAGEN 234
FT /note="T->A: Strongly decreased affinity for
FT acetylcholine."
FT /evidence="ECO:0000269|PubMed:1527051,
FT ECO:0000269|PubMed:1657592"
FT MUTAGEN 506
FT /note="Y->F: Decreased affinity for acetylcholine."
FT /evidence="ECO:0000269|PubMed:1527051,
FT ECO:0000269|PubMed:1657592"
FT MUTAGEN 529
FT /note="Y->F: Decreased affinity for acetylcholine."
FT /evidence="ECO:0000269|PubMed:1657592"
FT MUTAGEN 533
FT /note="Y->F: Decreased affinity for acetylcholine."
FT /evidence="ECO:0000269|PubMed:1657592"
FT CONFLICT 184
FT /note="A -> R (in Ref. 1; AAA40661/AAA40662 and 4;
FT BAA36839)"
FT /evidence="ECO:0000305"
FT CONFLICT 516
FT /note="C -> R (in Ref. 3; AAA40659)"
FT /evidence="ECO:0000305"
FT CONFLICT 556
FT /note="T -> M (in Ref. 3; AAA40659)"
FT /evidence="ECO:0000305"
FT HELIX 65..94
FT /evidence="ECO:0007829|PDB:4U15"
FT STRAND 96..98
FT /evidence="ECO:0007829|PDB:5ZHP"
FT HELIX 102..118
FT /evidence="ECO:0007829|PDB:4U15"
FT HELIX 120..129
FT /evidence="ECO:0007829|PDB:4U15"
FT STRAND 130..132
FT /evidence="ECO:0007829|PDB:4U15"
FT HELIX 137..170
FT /evidence="ECO:0007829|PDB:4U15"
FT STRAND 173..175
FT /evidence="ECO:0007829|PDB:4U15"
FT TURN 176..178
FT /evidence="ECO:0007829|PDB:4U15"
FT HELIX 181..210
FT /evidence="ECO:0007829|PDB:4U15"
FT HELIX 224..226
FT /evidence="ECO:0007829|PDB:5ZHP"
FT HELIX 228..238
FT /evidence="ECO:0007829|PDB:4U15"
FT HELIX 240..253
FT /evidence="ECO:0007829|PDB:4U15"
FT HELIX 255..257
FT /evidence="ECO:0007829|PDB:4U15"
FT HELIX 291..295
FT /evidence="ECO:0007829|PDB:5ZHP"
FT HELIX 304..307
FT /evidence="ECO:0007829|PDB:5ZHP"
FT HELIX 483..502
FT /evidence="ECO:0007829|PDB:4U15"
FT HELIX 504..513
FT /evidence="ECO:0007829|PDB:4U15"
FT STRAND 517..519
FT /evidence="ECO:0007829|PDB:4DAJ"
FT HELIX 522..533
FT /evidence="ECO:0007829|PDB:4U15"
FT HELIX 535..544
FT /evidence="ECO:0007829|PDB:4U15"
FT HELIX 548..556
FT /evidence="ECO:0007829|PDB:4U15"
SQ SEQUENCE 589 AA; 66066 MW; 9A5EF2FA653C830A CRC64;
MTLHSNSTTS PLFPNISSSW VHSPSEAGLP LGTVTQLGSY NISQETGNFS SNDTSSDPLG
GHTIWQVVFI AFLTGFLALV TIIGNILVIV AFKVNKQLKT VNNYFLLSLA CADLIIGVIS
MNLFTTYIIM NRWALGNLAC DLWLSIDYVA SNASVMNLLV ISFDRYFSIT RPLTYRAKRT
TKRAGVMIGL AWVISFVLWA PAILFWQYFV GKRTVPPGEC FIQFLSEPTI TFGTAIAAFY
MPVTIMTILY WRIYKETEKR TKELAGLQAS GTEAEAENFV HPTGSSRSCS SYELQQQGVK
RSSRRKYGRC HFWFTTKSWK PSAEQMDQDH SSSDSWNNND AAASLENSAS SDEEDIGSET
RAIYSIVLKL PGHSSILNST KLPSSDNLQV SNEDLGTVDV ERNAHKLQAQ KSMGDGDNCQ
KDFTKLPIQL ESAVDTGKTS DTNSSADKTT ATLPLSFKEA TLAKRFALKT RSQITKRKRM
SLIKEKKAAQ TLSAILLAFI ITWTPYNIMV LVNTFCDSCI PKTYWNLGYW LCYINSTVNP
VCYALCNKTF RTTFKTLLLC QCDKRKRRKQ QYQQRQSVIF HKRVPEQAL
