ID ACM5_HUMAN Reviewed; 532 AA. AC P08912; Q96RG7; DT 01-NOV-1988, integrated into UniProtKB/Swiss-Prot. DT 01-JUN-1994, sequence version 2. DT 27-MAR-2024, entry version 211. DE RecName: Full=Muscarinic acetylcholine receptor M5; GN Name=CHRM5; 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=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 [2] RP NUCLEOTIDE SEQUENCE [MRNA]. RC TISSUE=Lens epithelium; RA Rae J.L., Shepard A.R.; RL Submitted (SEP-1997) to the EMBL/GenBank/DDBJ databases. RN [3] RP NUCLEOTIDE SEQUENCE [MRNA]. RC TISSUE=Brain; RA Wang H., Yeomans J.; RT "Human muscarinic acetylcholine receptor 5 is localized on 15q13.1 and its RT expression in SH-SY5Y cells."; RL Submitted (APR-2002) to the EMBL/GenBank/DDBJ databases. 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 [MRNA] OF 1-526. RC TISSUE=Keratinocyte; RA Arredondo J., Grando S.A.; RT "Cloning cholinergic receptors in human keratinocytes."; RL Submitted (MAY-2001) to the EMBL/GenBank/DDBJ databases. 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. CC -!- INTERACTION: CC P08912; P20309: CHRM3; NbExp=7; IntAct=EBI-6655256, EBI-2687785; 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. CHRM5 sub-subfamily. CC {ECO:0000255|PROSITE-ProRule:PRU00521}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; M80333; AAA51569.1; -; Genomic_DNA. DR EMBL; AF026263; AAB95158.1; -; mRNA. DR EMBL; AB084282; BAB91222.1; -; mRNA. DR EMBL; AF498919; AAM18942.1; -; mRNA. DR EMBL; AF385591; AAK68116.1; -; mRNA. DR CCDS; CCDS10031.1; -. DR PIR; JT0530; JT0530. DR RefSeq; NP_001307846.1; NM_001320917.1. DR RefSeq; NP_036257.1; NM_012125.3. DR PDB; 6OL9; X-ray; 2.54 A; A=21-224, A=431-532. DR PDBsum; 6OL9; -. DR AlphaFoldDB; P08912; -. DR SMR; P08912; -. DR BioGRID; 107555; 37. DR IntAct; P08912; 30. DR MINT; P08912; -. DR STRING; 9606.ENSP00000372750; -. DR BindingDB; P08912; -. DR ChEMBL; CHEMBL2035; -. 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; 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; DB00483; Gallamine triethiodide. DR DrugBank; DB00986; Glycopyrronium. DR DrugBank; DB11181; Homatropine. DR DrugBank; DB00725; Homatropine methylbromide. DR DrugBank; DB00458; Imipramine. 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; DB00715; Paroxetine. 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; DB00726; Trimipramine. DR DrugBank; DB09076; Umeclidinium. DR DrugBank; DB00246; Ziprasidone. DR DrugCentral; P08912; -. DR GuidetoPHARMACOLOGY; 17; -. DR GlyCosmos; P08912; 1 site, No reported glycans. DR GlyGen; P08912; 1 site. DR iPTMnet; P08912; -. DR PhosphoSitePlus; P08912; -. DR BioMuta; CHRM5; -. DR DMDM; 543761; -. DR PaxDb; 9606-ENSP00000372750; -. DR PeptideAtlas; P08912; -. DR ProteomicsDB; 52175; -. DR Antibodypedia; 2963; 279 antibodies from 29 providers. DR DNASU; 1133; -. DR Ensembl; ENST00000383263.7; ENSP00000372750.5; ENSG00000184984.10. DR Ensembl; ENST00000557872.1; ENSP00000453745.1; ENSG00000184984.10. DR GeneID; 1133; -. DR KEGG; hsa:1133; -. DR MANE-Select; ENST00000383263.7; ENSP00000372750.5; NM_012125.4; NP_036257.1. DR UCSC; uc001zhk.2; human. DR AGR; HGNC:1954; -. DR CTD; 1133; -. DR DisGeNET; 1133; -. DR GeneCards; CHRM5; -. DR HGNC; HGNC:1954; CHRM5. DR HPA; ENSG00000184984; Tissue enriched (brain). DR MIM; 118496; gene. DR neXtProt; NX_P08912; -. DR OpenTargets; ENSG00000184984; -. DR PharmGKB; PA26486; -. DR VEuPathDB; HostDB:ENSG00000184984; -. DR eggNOG; KOG4220; Eukaryota. DR GeneTree; ENSGT00940000158450; -. DR HOGENOM; CLU_009579_11_2_1; -. DR InParanoid; P08912; -. DR OMA; YDTPKYF; -. DR OrthoDB; 4136179at2759; -. DR PhylomeDB; P08912; -. DR TreeFam; TF320495; -. DR PathwayCommons; P08912; -. DR Reactome; R-HSA-390648; Muscarinic acetylcholine receptors. DR Reactome; R-HSA-416476; G alpha (q) signalling events. DR SignaLink; P08912; -. DR SIGNOR; P08912; -. DR BioGRID-ORCS; 1133; 13 hits in 1157 CRISPR screens. DR GeneWiki; Muscarinic_acetylcholine_receptor_M5; -. DR GenomeRNAi; 1133; -. DR Pharos; P08912; Tclin. DR PRO; PR:P08912; -. DR Proteomes; UP000005640; Chromosome 15. DR RNAct; P08912; Protein. DR Bgee; ENSG00000184984; Expressed in male germ line stem cell (sensu Vertebrata) in testis and 80 other cell types or tissues. DR ExpressionAtlas; P08912; baseline and differential. 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:0004435; F:phosphatidylinositol phospholipase C activity; TAS:ProtInc. DR GO; GO:0007197; P:adenylate cyclase-inhibiting G protein-coupled acetylcholine receptor signaling pathway; IBA:GO_Central. DR GO; GO:0007268; P:chemical synaptic transmission; IBA:GO_Central. DR GO; GO:0015872; P:dopamine transport; IEA:Ensembl. 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:0001696; P:gastric acid secretion; IEA:InterPro. DR GO; GO:0060304; P:regulation of phosphatidylinositol dephosphorylation; IEA:Ensembl. DR GO; GO:0019226; P:transmission of nerve impulse; IEA:Ensembl. DR CDD; cd15300; 7tmA_mAChR_M5; 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; IPR000502; Musac_Ach_M5_rcpt. DR InterPro; IPR000995; Musac_Ach_rcpt. DR PANTHER; PTHR24247; 5-HYDROXYTRYPTAMINE RECEPTOR; 1. DR PANTHER; PTHR24247:SF209; MUSCARINIC ACETYLCHOLINE RECEPTOR M5; 1. DR Pfam; PF00001; 7tm_1; 2. DR PRINTS; PR00237; GPCRRHODOPSN. DR PRINTS; PR00243; MUSCARINICR. DR PRINTS; PR00542; MUSCRINICM5R. 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; P08912; 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..532 FT /note="Muscarinic acetylcholine receptor M5" FT /id="PRO_0000069042" FT TOPO_DOM 1..29 FT /note="Extracellular" FT /evidence="ECO:0000250" FT TRANSMEM 30..53 FT /note="Helical; Name=1" FT /evidence="ECO:0000250" FT TOPO_DOM 54..66 FT /note="Cytoplasmic" FT /evidence="ECO:0000250" FT TRANSMEM 67..87 FT /note="Helical; Name=2" FT /evidence="ECO:0000250" FT TOPO_DOM 88..104 FT /note="Extracellular" FT /evidence="ECO:0000250" FT TRANSMEM 105..126 FT /note="Helical; Name=3" FT /evidence="ECO:0000250" FT TOPO_DOM 127..146 FT /note="Cytoplasmic" FT /evidence="ECO:0000250" FT TRANSMEM 147..169 FT /note="Helical; Name=4" FT /evidence="ECO:0000250" FT TOPO_DOM 170..191 FT /note="Extracellular" FT /evidence="ECO:0000250" FT TRANSMEM 192..214 FT /note="Helical; Name=5" FT /evidence="ECO:0000250" FT TOPO_DOM 215..443 FT /note="Cytoplasmic" FT /evidence="ECO:0000250" FT TRANSMEM 444..464 FT /note="Helical; Name=6" FT /evidence="ECO:0000250" FT TOPO_DOM 465..478 FT /note="Extracellular" FT /evidence="ECO:0000250" FT TRANSMEM 479..498 FT /note="Helical; Name=7" FT /evidence="ECO:0000250" FT TOPO_DOM 499..532 FT /note="Cytoplasmic" FT /evidence="ECO:0000250" FT REGION 262..294 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 263..294 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT MOD_RES 501 FT /note="Phosphothreonine" FT /evidence="ECO:0000255" FT MOD_RES 505 FT /note="Phosphothreonine" FT /evidence="ECO:0000255" FT CARBOHYD 8 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT DISULFID 103..183 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00521" FT CONFLICT 526 FT /note="Q -> P (in Ref. 5)" FT /evidence="ECO:0000305" FT HELIX 27..57 FT /evidence="ECO:0007829|PDB:6OL9" FT HELIX 59..61 FT /evidence="ECO:0007829|PDB:6OL9" FT HELIX 64..81 FT /evidence="ECO:0007829|PDB:6OL9" FT HELIX 83..93 FT /evidence="ECO:0007829|PDB:6OL9" FT HELIX 100..133 FT /evidence="ECO:0007829|PDB:6OL9" FT TURN 135..138 FT /evidence="ECO:0007829|PDB:6OL9" FT HELIX 139..141 FT /evidence="ECO:0007829|PDB:6OL9" FT HELIX 144..173 FT /evidence="ECO:0007829|PDB:6OL9" FT HELIX 187..189 FT /evidence="ECO:0007829|PDB:6OL9" FT HELIX 191..201 FT /evidence="ECO:0007829|PDB:6OL9" FT HELIX 203..218 FT /evidence="ECO:0007829|PDB:6OL9" FT HELIX 431..466 FT /evidence="ECO:0007829|PDB:6OL9" FT STRAND 468..470 FT /evidence="ECO:0007829|PDB:6OL9" FT HELIX 474..498 FT /evidence="ECO:0007829|PDB:6OL9" FT HELIX 500..511 FT /evidence="ECO:0007829|PDB:6OL9" SQ SEQUENCE 532 AA; 60074 MW; EE846186F645DD9B CRC64; MEGDSYHNAT TVNGTPVNHQ PLERHRLWEV ITIAAVTAVV SLITIVGNVL VMISFKVNSQ LKTVNNYYLL SLACADLIIG IFSMNLYTTY ILMGRWALGS LACDLWLALD YVASNASVMN LLVISFDRYF SITRPLTYRA KRTPKRAGIM IGLAWLISFI LWAPAILCWQ YLVGKRTVPL DECQIQFLSE PTITFGTAIA AFYIPVSVMT ILYCRIYRET EKRTKDLADL QGSDSVTKAE KRKPAHRALF RSCLRCPRPT LAQRERNQAS WSSSRRSTST TGKPSQATGP SANWAKAEQL TTCSSYPSSE DEDKPATDPV LQVVYKSQGK ESPGEEFSAE ETEETFVKAE TEKSDYDTPN YLLSPAAAHR PKSQKCVAYK FRLVVKADGN QETNNGCHKV KIMPCPFPVA KEPSTKGLNP NPSHQMTKRK RVVLVKERKA AQTLSAILLA FIITWTPYNI MVLVSTFCDK CVPVTLWHLG YWLCYVNSTV NPICYALCNR TFRKTFKMLL LCRWKKKKVE EKLYWQGNSK LP //