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   02-SEP-2026, entry version 221.
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       P08912; O60894: RAMP1; NbExp=2; IntAct=EBI-6655256, EBI-962893;
CC       P08912; O60895: RAMP2; NbExp=3; IntAct=EBI-6655256, EBI-9009040;
CC       P08912; O60896: RAMP3; NbExp=3; IntAct=EBI-6655256, EBI-720447;
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_001320917.2.
DR   RefSeq; NP_036257.1; NM_012125.4.
DR   PDB; 6OL9; X-ray; 2.54 A; A=21-224, A=431-532.
DR   PDB; 9EK0; EM; 2.79 A; R=2-521.
DR   AlphaFoldDB; P08912; -.
DR   EMDB; EMD-48110; -.
DR   EMDB; EMD-48111; -.
DR   MDRepo; P08912; -.
DR   SMR; P08912; -.
DR   BioGRID; 107555; 37.
DR   CORUM; P08912; -.
DR   FunCoup; P08912; 1133.
DR   IntAct; P08912; 40.
DR   MINT; P08912; -.
DR   NDEx; IQUERY-CP-CHRM5; 5 NDEx IQuery Curated Pathways.
DR   STRING; 9606.ENSP00000372750; -.
DR   BindingDB; P08912; -.
DR   ChEMBL; CHEMBL2035; -.
DR   DrugBank; DB13262; Aceclidine.
DR   DrugBank; DB08897; Aclidinium.
DR   DrugBank; DB05752; ALKS 27.
DR   DrugBank; DB00321; Amitriptyline.
DR   DrugBank; DB00543; Amoxapine.
DR   DrugBank; DB00517; Anisotropine methylbromide.
DR   DrugBank; DB01238; Aripiprazole.
DR   DrugBank; DB14185; Aripiprazole lauroxil.
DR   DrugBank; DB00572; Atropine.
DR   DrugBank; DB09023; Benactyzine.
DR   DrugBank; DB00767; Benzquinamide.
DR   DrugBank; DB01019; Bethanechol.
DR   DrugBank; DB00835; Brompheniramine.
DR   DrugBank; DB15968; Butropium.
DR   DrugBank; DB09300; Butylscopolamine.
DR   DrugBank; DB11960; Carboxyamidotriazole.
DR   DrugBank; DB01239; Chlorprothixene.
DR   DrugBank; DB04660; Choline alfoscerate.
DR   DrugBank; DB09271; Cimetropium.
DR   DrugBank; DB00568; Cinnarizine.
DR   DrugBank; DB00363; Clozapine.
DR   DrugBank; DB00979; Cyclopentolate.
DR   DrugBank; DB00496; Darifenacin.
DR   DrugBank; DB01151; Desipramine.
DR   DrugBank; DB09167; Dosulepin.
DR   DrugBank; DB01142; Doxepin.
DR   DrugBank; DB00366; Doxylamine.
DR   DrugBank; DB13505; Emepronium.
DR   DrugBank; DB09194; Etoperidone.
DR   DrugBank; DB06702; Fesoterodine.
DR   DrugBank; DB01148; Flavoxate.
DR   DrugBank; DB00483; Gallamine triethiodide.
DR   DrugBank; DB00986; Glycopyrronium.
DR   DrugBank; DB11181; Homatropine.
DR   DrugBank; DB00725; Homatropine methylbromide.
DR   DrugBank; DB00424; Hyoscyamine.
DR   DrugBank; DB00458; Imipramine.
DR   DrugBank; DB01221; Ketamine.
DR   DrugBank; DB00408; Loxapine.
DR   DrugBank; DB00934; Maprotiline.
DR   DrugBank; DB12554; Mebeverine.
DR   DrugBank; DB04843; Mepenzolate.
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; DB12086; Oxitropium.
DR   DrugBank; DB00383; Oxyphencyclimine.
DR   DrugBank; DB00715; Paroxetine.
DR   DrugBank; DB01085; Pilocarpine.
DR   DrugBank; DB14585; Plantago ovata seed.
DR   DrugBank; DB13247; Pramiracetam.
DR   DrugBank; DB13254; Prifinium.
DR   DrugBank; DB00387; Procyclidine.
DR   DrugBank; DB00420; Promazine.
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; DB19325; Sofpironium.
DR   DrugBank; DB01591; Solifenacin.
DR   DrugBank; DB00342; Terfenadine.
DR   DrugBank; DB11235; Thonzylamine.
DR   DrugBank; DB01409; Tiotropium.
DR   DrugBank; DB01036; Tolterodine.
DR   DrugBank; DB00505; Tridihexethyl.
DR   DrugBank; DB00376; Trihexyphenidyl.
DR   DrugBank; DB00726; Trimipramine.
DR   DrugBank; DB00209; Trospium.
DR   DrugBank; DB09076; Umeclidinium.
DR   DrugBank; DB15357; Xanomeline.
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; 250 antibodies from 31 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   ClinPGx; PA26486; -.
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   OpenTargets; ENSG00000184984; -.
DR   VEuPathDB; HostDB:ENSG00000184984; -.
DR   eggNOG; KOG4220; Eukaryota.
DR   GeneTree; ENSGT00940000158450; -.
DR   HOGENOM; CLU_009579_11_2_1; -.
DR   InParanoid; P08912; -.
DR   OMA; IPVTLWH; -.
DR   OrthoDB; 10071887at2759; -.
DR   PAN-GO; P08912; 7 GO annotations based on evolutionary models.
DR   PhylomeDB; P08912; -.
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   Agora; ENSG00000184984; -.
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; IBA:GO_Central.
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:0004435; F:phosphatidylinositol-4,5-bisphosphate 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: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   CDD; cd15300; 7tmA_mAChR_M5; 1.
DR   FunFam; 1.20.1070.10:FF:000047; Muscarinic acetylcholine receptor; 1.
DR   FunFam; 1.20.1070.10:FF:000164; Muscarinic acetylcholine receptor; 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; 1.
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   PDBsum; 6OL9; -.
DR   PDBsum; 9EK0; -.
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   Proteomics identification; Receptor; Reference proteome; Synapse;
KW   Transducer; Transmembrane; 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        270..281
FT                   /note="Low complexity"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        282..291
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..78
FT                   /evidence="ECO:0007829|PDB:6OL9"
FT   HELIX           79..83
FT                   /evidence="ECO:0007829|PDB:6OL9"
FT   HELIX           84..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..198
FT                   /evidence="ECO:0007829|PDB:6OL9"
FT   HELIX           199..203
FT                   /evidence="ECO:0007829|PDB:6OL9"
FT   HELIX           204..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
//