ID   ACM4_HUMAN              Reviewed;         479 AA.
AC   P08173; B2RPP4; Q0VD60; Q4VBK7;
DT   01-AUG-1988, integrated into UniProtKB/Swiss-Prot.
DT   19-SEP-2002, sequence version 2.
DT   27-MAR-2024, entry version 201.
DE   RecName: Full=Muscarinic acetylcholine receptor M4;
GN   Name=CHRM4;
OS   Homo sapiens (Human).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC   Homo.
OX   NCBI_TaxID=9606;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
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 258 AND 261-266.
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 [GENOMIC DNA].
RX   PubMed=3443095; DOI=10.1002/j.1460-2075.1987.tb02733.x;
RA   Peralta E.G., Ashkenazi A., Winslow J.W., Smith D.H., Ramachandran J.,
RA   Capon D.J.;
RT   "Distinct primary structures, ligand-binding properties and tissue-specific
RT   expression of four human muscarinic acetylcholine receptors.";
RL   EMBO J. 6:3923-3929(1987).
RN   [4]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   TISSUE=Brain;
RA   Puhl H.L. III, Ikeda S.R., Aronstam R.S.;
RT   "cDNA clones of human proteins involved in signal transduction sequenced by
RT   the Guthrie cDNA resource center (www.cdna.org).";
RL   Submitted (APR-2002) to the EMBL/GenBank/DDBJ databases.
RN   [5]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA   Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA   Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA   Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA   Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA   Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA   Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA   Hunkapiller M.W., Myers E.W., Venter J.C.;
RL   Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN   [6]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RX   PubMed=15489334; DOI=10.1101/gr.2596504;
RG   The MGC Project Team;
RT   "The status, quality, and expansion of the NIH full-length cDNA project:
RT   the Mammalian Gene Collection (MGC).";
RL   Genome Res. 14:2121-2127(2004).
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
CC       inhibition of adenylate cyclase.
CC   -!- SUBCELLULAR LOCATION: Cell membrane; Multi-pass membrane protein.
CC       Postsynaptic cell membrane; Multi-pass membrane protein.
CC   -!- SIMILARITY: Belongs to the G-protein coupled receptor 1 family.
CC       Muscarinic acetylcholine receptor subfamily. CHRM4 sub-subfamily.
CC       {ECO:0000255|PROSITE-ProRule:PRU00521}.
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DR   EMBL; M16405; AAA51571.2; -; Genomic_DNA.
DR   EMBL; X15265; CAA33336.1; -; Genomic_DNA.
DR   EMBL; AF498918; AAM18941.1; -; mRNA.
DR   EMBL; CH471064; EAW68004.1; -; Genomic_DNA.
DR   EMBL; BC095546; AAH95546.1; -; mRNA.
DR   EMBL; BC119775; AAI19776.1; -; mRNA.
DR   EMBL; BC119817; AAI19818.1; -; mRNA.
DR   EMBL; BC137535; AAI37536.1; -; mRNA.
DR   CCDS; CCDS44581.1; -.
DR   PIR; S10127; S10127.
DR   RefSeq; NP_000732.2; NM_000741.3.
DR   PDB; 5DSG; X-ray; 2.60 A; A/B=22-226, A/B=390-478.
DR   PDB; 6D9H; EM; 3.60 A; R=2-23.
DR   PDB; 6KP6; X-ray; 3.00 A; A=22-227, A=390-479.
DR   PDB; 7LD3; EM; 3.20 A; R=2-23.
DR   PDB; 7LD4; EM; 3.30 A; R=2-23.
DR   PDB; 7TRK; EM; 2.80 A; R=1-479.
DR   PDB; 7TRP; EM; 2.40 A; R=1-479.
DR   PDB; 7TRQ; EM; 2.50 A; R=1-479.
DR   PDB; 7TRS; EM; 2.80 A; R=1-479.
DR   PDB; 7V68; EM; 3.40 A; R=1-479.
DR   PDB; 7V69; EM; 3.40 A; R=1-479.
DR   PDB; 7V6A; EM; 3.60 A; R=1-479.
DR   PDB; 8E9X; EM; 2.70 A; A=1-479.
DR   PDB; 8FX5; EM; 2.45 A; R=1-479.
DR   PDBsum; 5DSG; -.
DR   PDBsum; 6D9H; -.
DR   PDBsum; 6KP6; -.
DR   PDBsum; 7LD3; -.
DR   PDBsum; 7LD4; -.
DR   PDBsum; 7TRK; -.
DR   PDBsum; 7TRP; -.
DR   PDBsum; 7TRQ; -.
DR   PDBsum; 7TRS; -.
DR   PDBsum; 7V68; -.
DR   PDBsum; 7V69; -.
DR   PDBsum; 7V6A; -.
DR   PDBsum; 8E9X; -.
DR   PDBsum; 8FX5; -.
DR   AlphaFoldDB; P08173; -.
DR   EMDB; EMD-23280; -.
DR   EMDB; EMD-23281; -.
DR   EMDB; EMD-26099; -.
DR   EMDB; EMD-26100; -.
DR   EMDB; EMD-26101; -.
DR   EMDB; EMD-26102; -.
DR   EMDB; EMD-27967; -.
DR   EMDB; EMD-29524; -.
DR   EMDB; EMD-31738; -.
DR   EMDB; EMD-31739; -.
DR   EMDB; EMD-31740; -.
DR   EMDB; EMD-7835; -.
DR   SMR; P08173; -.
DR   BioGRID; 107554; 93.
DR   DIP; DIP-61455N; -.
DR   IntAct; P08173; 80.
DR   MINT; P08173; -.
DR   STRING; 9606.ENSP00000409378; -.
DR   BindingDB; P08173; -.
DR   ChEMBL; CHEMBL1821; -.
DR   DrugBank; DB03128; Acetylcholine.
DR   DrugBank; DB08897; Aclidinium.
DR   DrugBank; DB05752; ALKS 27.
DR   DrugBank; DB00321; Amitriptyline.
DR   DrugBank; DB00543; Amoxapine.
DR   DrugBank; DB01238; Aripiprazole.
DR   DrugBank; DB14185; Aripiprazole lauroxil.
DR   DrugBank; DB00572; Atropine.
DR   DrugBank; DB00767; Benzquinamide.
DR   DrugBank; DB01019; Bethanechol.
DR   DrugBank; DB00835; Brompheniramine.
DR   DrugBank; DB00411; Carbamoylcholine.
DR   DrugBank; DB01239; Chlorprothixene.
DR   DrugBank; DB00568; Cinnarizine.
DR   DrugBank; DB00363; Clozapine.
DR   DrugBank; DB00496; Darifenacin.
DR   DrugBank; DB01151; Desipramine.
DR   DrugBank; DB09167; Dosulepin.
DR   DrugBank; DB01142; Doxepin.
DR   DrugBank; DB00366; Doxylamine.
DR   DrugBank; DB09194; Etoperidone.
DR   DrugBank; DB06702; Fesoterodine.
DR   DrugBank; DB00986; Glycopyrronium.
DR   DrugBank; DB06787; Hexocyclium.
DR   DrugBank; DB11181; Homatropine.
DR   DrugBank; DB00725; Homatropine methylbromide.
DR   DrugBank; DB00424; Hyoscyamine.
DR   DrugBank; DB00458; Imipramine.
DR   DrugBank; DB01625; Isopropamide.
DR   DrugBank; DB01221; Ketamine.
DR   DrugBank; DB00408; Loxapine.
DR   DrugBank; DB00934; Maprotiline.
DR   DrugBank; DB00454; Meperidine.
DR   DrugBank; DB06709; Methacholine.
DR   DrugBank; DB00940; Methantheline.
DR   DrugBank; DB01403; Methotrimeprazine.
DR   DrugBank; DB00340; Metixene.
DR   DrugBank; DB00622; Nicardipine.
DR   DrugBank; DB00540; Nortriptyline.
DR   DrugBank; DB00334; Olanzapine.
DR   DrugBank; DB00715; Paroxetine.
DR   DrugBank; DB01085; Pilocarpine.
DR   DrugBank; DB00387; Procyclidine.
DR   DrugBank; DB01069; Promethazine.
DR   DrugBank; DB00777; Propiomazine.
DR   DrugBank; DB12278; Propiverine.
DR   DrugBank; DB01224; Quetiapine.
DR   DrugBank; DB11855; Revefenacin.
DR   DrugBank; DB13581; Rociverine.
DR   DrugBank; DB00747; Scopolamine.
DR   DrugBank; DB01591; Solifenacin.
DR   DrugBank; DB00342; Terfenadine.
DR   DrugBank; DB11235; Thonzylamine.
DR   DrugBank; DB01409; Tiotropium.
DR   DrugBank; DB01036; Tolterodine.
DR   DrugBank; DB00376; Trihexyphenidyl.
DR   DrugBank; DB09089; Trimebutine.
DR   DrugBank; DB00726; Trimipramine.
DR   DrugBank; DB00809; Tropicamide.
DR   DrugBank; DB09076; Umeclidinium.
DR   DrugBank; DB09185; Viloxazine.
DR   DrugBank; DB00246; Ziprasidone.
DR   DrugCentral; P08173; -.
DR   GuidetoPHARMACOLOGY; 16; -.
DR   GlyCosmos; P08173; 2 sites, No reported glycans.
DR   GlyGen; P08173; 2 sites.
DR   iPTMnet; P08173; -.
DR   PhosphoSitePlus; P08173; -.
DR   BioMuta; CHRM4; -.
DR   DMDM; 23503039; -.
DR   MassIVE; P08173; -.
DR   PaxDb; 9606-ENSP00000409378; -.
DR   PeptideAtlas; P08173; -.
DR   Antibodypedia; 26327; 264 antibodies from 30 providers.
DR   DNASU; 1132; -.
DR   Ensembl; ENST00000433765.3; ENSP00000409378.2; ENSG00000180720.8.
DR   Ensembl; ENST00000682254.1; ENSP00000507561.1; ENSG00000180720.8.
DR   GeneID; 1132; -.
DR   KEGG; hsa:1132; -.
DR   MANE-Select; ENST00000682254.1; ENSP00000507561.1; NM_000741.5; NP_000732.2.
DR   UCSC; uc001nct.2; human.
DR   AGR; HGNC:1953; -.
DR   CTD; 1132; -.
DR   DisGeNET; 1132; -.
DR   GeneCards; CHRM4; -.
DR   HGNC; HGNC:1953; CHRM4.
DR   HPA; ENSG00000180720; Tissue enhanced (brain, intestine, lymphoid tissue).
DR   MIM; 118495; gene.
DR   neXtProt; NX_P08173; -.
DR   OpenTargets; ENSG00000180720; -.
DR   PharmGKB; PA26485; -.
DR   VEuPathDB; HostDB:ENSG00000180720; -.
DR   eggNOG; KOG4220; Eukaryota.
DR   GeneTree; ENSGT00940000160394; -.
DR   HOGENOM; CLU_009579_11_2_1; -.
DR   InParanoid; P08173; -.
DR   OMA; YKTVEMV; -.
DR   OrthoDB; 4136179at2759; -.
DR   PhylomeDB; P08173; -.
DR   TreeFam; TF320495; -.
DR   PathwayCommons; P08173; -.
DR   Reactome; R-HSA-390648; Muscarinic acetylcholine receptors.
DR   Reactome; R-HSA-418594; G alpha (i) signalling events.
DR   SignaLink; P08173; -.
DR   SIGNOR; P08173; -.
DR   BioGRID-ORCS; 1132; 18 hits in 1151 CRISPR screens.
DR   GeneWiki; Muscarinic_acetylcholine_receptor_M4; -.
DR   GenomeRNAi; 1132; -.
DR   Pharos; P08173; Tclin.
DR   PRO; PR:P08173; -.
DR   Proteomes; UP000005640; Chromosome 11.
DR   RNAct; P08173; Protein.
DR   Bgee; ENSG00000180720; Expressed in male germ line stem cell (sensu Vertebrata) in testis and 86 other cell types or tissues.
DR   GO; GO:0030425; C:dendrite; IBA:GO_Central.
DR   GO; GO:0005886; C:plasma membrane; TAS:Reactome.
DR   GO; GO:0045211; C:postsynaptic membrane; IEA:UniProtKB-SubCell.
DR   GO; GO:0045202; C:synapse; IBA:GO_Central.
DR   GO; GO:0016907; F:G protein-coupled acetylcholine receptor activity; IBA:GO_Central.
DR   GO; GO:0004993; F:G protein-coupled serotonin receptor activity; IBA:GO_Central.
DR   GO; GO:0007197; P:adenylate cyclase-inhibiting G protein-coupled acetylcholine receptor signaling pathway; IBA:GO_Central.
DR   GO; GO:0007166; P:cell surface receptor signaling pathway; TAS:ProtInc.
DR   GO; GO:0007268; P:chemical synaptic transmission; IBA:GO_Central.
DR   GO; GO:0007213; P:G protein-coupled acetylcholine receptor signaling pathway; TAS:ProtInc.
DR   GO; GO:0007187; P:G protein-coupled receptor signaling pathway, coupled to cyclic nucleotide second messenger; IBA:GO_Central.
DR   GO; GO:0040012; P:regulation of locomotion; IEA:InterPro.
DR   GO; GO:0007165; P:signal transduction; TAS:ProtInc.
DR   CDD; cd15298; 7tmA_mAChR_M4; 1.
DR   Gene3D; 1.20.1070.10; Rhodopsin 7-helix transmembrane proteins; 2.
DR   InterPro; IPR000276; GPCR_Rhodpsn.
DR   InterPro; IPR017452; GPCR_Rhodpsn_7TM.
DR   InterPro; IPR001432; Musac_Ach_M4_rcpt.
DR   InterPro; IPR000995; Musac_Ach_rcpt.
DR   PANTHER; PTHR24247; 5-HYDROXYTRYPTAMINE RECEPTOR; 1.
DR   PANTHER; PTHR24247:SF180; MUSCARINIC ACETYLCHOLINE RECEPTOR M4; 1.
DR   Pfam; PF00001; 7tm_1; 1.
DR   PRINTS; PR00237; GPCRRHODOPSN.
DR   PRINTS; PR00243; MUSCARINICR.
DR   PRINTS; PR00541; MUSCRINICM4R.
DR   SMART; SM01381; 7TM_GPCR_Srsx; 1.
DR   SUPFAM; SSF81321; Family A G protein-coupled receptor-like; 1.
DR   PROSITE; PS00237; G_PROTEIN_RECEP_F1_1; 1.
DR   PROSITE; PS50262; G_PROTEIN_RECEP_F1_2; 1.
DR   Genevisible; P08173; HS.
PE   1: Evidence at protein level;
KW   3D-structure; Cell membrane; Disulfide bond; G-protein coupled receptor;
KW   Glycoprotein; Membrane; Phosphoprotein; Postsynaptic cell membrane;
KW   Receptor; Reference proteome; Synapse; Transducer; Transmembrane;
KW   Transmembrane helix.
FT   CHAIN           1..479
FT                   /note="Muscarinic acetylcholine receptor M4"
FT                   /id="PRO_0000069037"
FT   TOPO_DOM        1..31
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000250"
FT   TRANSMEM        32..54
FT                   /note="Helical; Name=1"
FT                   /evidence="ECO:0000250"
FT   TOPO_DOM        55..68
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000250"
FT   TRANSMEM        69..89
FT                   /note="Helical; Name=2"
FT                   /evidence="ECO:0000250"
FT   TOPO_DOM        90..106
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000250"
FT   TRANSMEM        107..128
FT                   /note="Helical; Name=3"
FT                   /evidence="ECO:0000250"
FT   TOPO_DOM        129..148
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000250"
FT   TRANSMEM        149..171
FT                   /note="Helical; Name=4"
FT                   /evidence="ECO:0000250"
FT   TOPO_DOM        172..193
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000250"
FT   TRANSMEM        194..216
FT                   /note="Helical; Name=5"
FT                   /evidence="ECO:0000250"
FT   TOPO_DOM        217..401
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000250"
FT   TRANSMEM        402..422
FT                   /note="Helical; Name=6"
FT                   /evidence="ECO:0000250"
FT   TOPO_DOM        423..436
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000250"
FT   TRANSMEM        437..456
FT                   /note="Helical; Name=7"
FT                   /evidence="ECO:0000250"
FT   TOPO_DOM        457..479
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000250"
FT   REGION          271..333
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        290..322
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   MOD_RES         459
FT                   /note="Phosphothreonine"
FT                   /evidence="ECO:0000255"
FT   MOD_RES         463
FT                   /note="Phosphothreonine"
FT                   /evidence="ECO:0000255"
FT   MOD_RES         477
FT                   /note="Phosphothreonine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        8
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        13
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   DISULFID        105..185
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00521"
FT   HELIX           26..59
FT                   /evidence="ECO:0007829|PDB:5DSG"
FT   HELIX           61..63
FT                   /evidence="ECO:0007829|PDB:5DSG"
FT   HELIX           66..83
FT                   /evidence="ECO:0007829|PDB:5DSG"
FT   HELIX           85..95
FT                   /evidence="ECO:0007829|PDB:5DSG"
FT   HELIX           101..135
FT                   /evidence="ECO:0007829|PDB:5DSG"
FT   TURN            137..140
FT                   /evidence="ECO:0007829|PDB:5DSG"
FT   HELIX           141..143
FT                   /evidence="ECO:0007829|PDB:5DSG"
FT   HELIX           146..169
FT                   /evidence="ECO:0007829|PDB:5DSG"
FT   HELIX           171..175
FT                   /evidence="ECO:0007829|PDB:5DSG"
FT   STRAND          182..184
FT                   /evidence="ECO:0007829|PDB:7V68"
FT   HELIX           188..190
FT                   /evidence="ECO:0007829|PDB:5DSG"
FT   HELIX           193..203
FT                   /evidence="ECO:0007829|PDB:5DSG"
FT   HELIX           205..220
FT                   /evidence="ECO:0007829|PDB:5DSG"
FT   STRAND          223..225
FT                   /evidence="ECO:0007829|PDB:5DSG"
FT   HELIX           226..229
FT                   /evidence="ECO:0007829|PDB:5DSG"
FT   HELIX           232..237
FT                   /evidence="ECO:0007829|PDB:5DSG"
FT   HELIX           397..422
FT                   /evidence="ECO:0007829|PDB:5DSG"
FT   TURN            423..425
FT                   /evidence="ECO:0007829|PDB:5DSG"
FT   STRAND          427..430
FT                   /evidence="ECO:0007829|PDB:7V69"
FT   HELIX           432..456
FT                   /evidence="ECO:0007829|PDB:5DSG"
FT   HELIX           458..468
FT                   /evidence="ECO:0007829|PDB:5DSG"
SQ   SEQUENCE   479 AA;  53049 MW;  9C1B05B359A64289 CRC64;
     MANFTPVNGS SGNQSVRLVT SSSHNRYETV EMVFIATVTG SLSLVTVVGN ILVMLSIKVN
     RQLQTVNNYF LFSLACADLI IGAFSMNLYT VYIIKGYWPL GAVVCDLWLA LDYVVSNASV
     MNLLIISFDR YFCVTKPLTY PARRTTKMAG LMIAAAWVLS FVLWAPAILF WQFVVGKRTV
     PDNQCFIQFL SNPAVTFGTA IAAFYLPVVI MTVLYIHISL ASRSRVHKHR PEGPKEKKAK
     TLAFLKSPLM KQSVKKPPPG EAAREELRNG KLEEAPPPAL PPPPRPVADK DTSNESSSGS
     ATQNTKERPA TELSTTEATT PAMPAPPLQP RALNPASRWS KIQIVTKQTG NECVTAIEIV
     PATPAGMRPA ANVARKFASI ARNQVRKKRQ MAARERKVTR TIFAILLAFI LTWTPYNVMV
     LVNTFCQSCI PDTVWSIGYW LCYVNSTINP ACYALCNATF KKTFRHLLLC QYRNIGTAR
//