ACM4_HUMAN
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 03-AUG-2022, entry version 192.
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 PDBsum; 5DSG; -.
DR PDBsum; 6D9H; -.
DR PDBsum; 6KP6; -.
DR PDBsum; 7LD3; -.
DR PDBsum; 7LD4; -.
DR AlphaFoldDB; P08173; -.
DR SMR; P08173; -.
DR BioGRID; 107554; 90.
DR DIP; DIP-61455N; -.
DR IntAct; P08173; 79.
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; DB00246; Ziprasidone.
DR DrugCentral; P08173; -.
DR GuidetoPHARMACOLOGY; 16; -.
DR GlyGen; P08173; 2 sites.
DR iPTMnet; P08173; -.
DR PhosphoSitePlus; P08173; -.
DR BioMuta; CHRM4; -.
DR DMDM; 23503039; -.
DR MassIVE; P08173; -.
DR PaxDb; P08173; -.
DR PeptideAtlas; P08173; -.
DR PRIDE; P08173; -.
DR ProteomicsDB; 52077; -.
DR Antibodypedia; 26327; 208 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 CTD; 1132; -.
DR DisGeNET; 1132; -.
DR GeneCards; CHRM4; -.
DR HGNC; HGNC:1953; CHRM4.
DR HPA; ENSG00000180720; Group enriched (brain, intestine, lymphoid tissue, testis).
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; 1245472at2759; -.
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; 15 hits in 1067 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 caudate nucleus and 85 other tissues.
DR Genevisible; P08173; HS.
DR GO; GO:0070161; C:anchoring junction; IEA:UniProtKB-KW.
DR GO; GO:0030425; C:dendrite; IBA:GO_Central.
DR GO; GO:0005887; C:integral component of plasma membrane; 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:0030594; F:neurotransmitter 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 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; PTHR24248:SF142; PTHR24248:SF142; 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 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; 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 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 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
