ID 5HT4R_RAT Reviewed; 406 AA. AC Q62758; O89034; Q62757; Q63006; DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot. DT 01-NOV-1996, sequence version 1. DT 08-NOV-2023, entry version 158. DE RecName: Full=5-hydroxytryptamine receptor 4; DE Short=5-HT-4; DE Short=5-HT4; DE AltName: Full=Serotonin receptor 4; GN Name=Htr4; 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 [MRNA]. RC TISSUE=Brain; RX PubMed=7796807; DOI=10.1002/j.1460-2075.1995.tb07280.x; RA Gerald C., Adham N., Kao H.T., Olsen M.A., Laz T.M., Schechter L.E., RA Bard J.A., Vaysse P., Hartig P.R., Branchek T.A., Weinshank R.L.; RT "The 5-HT4 receptor: molecular cloning and pharmacological characterization RT of two splice variants."; RL EMBO J. 14:2806-2815(1995). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] OF 165-259. RC TISSUE=Brain; RX PubMed=7656980; DOI=10.1016/0014-5793(95)00828-w; RA Ullmer C., Schmuck K., Kalkman H.O., Luebbert H.; RT "Expression of serotonin receptor mRNAs in blood vessels."; RL FEBS Lett. 370:215-221(1995). RN [3] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 5-HT4(E)). RC TISSUE=Brain; RX PubMed=10220570; RA Claeysen S., Sebben M., Becamel C., Bockaert J., Dumuis A.; RT "Novel brain-specific 5-HT4 receptor splice variants show marked RT constitutive activity: role of the C-terminal intracellular domain."; RL Mol. Pharmacol. 55:910-920(1999). CC -!- FUNCTION: This is one of the several different receptors for 5- CC hydroxytryptamine (serotonin), a biogenic hormone that functions as a CC neurotransmitter, a hormone, and a mitogen. The activity of this CC receptor is mediated by G proteins that stimulate adenylate cyclase. CC -!- SUBUNIT: May interact with PATJ, MAGI2, MPP3, NOS1, NHERF1, SEC23A and CC SNX27. May form a complex including NHERF1 and EZR (By similarity). CC Interacts (via C-terminus 330-346 AA) with GRK5; this interaction is CC promoted by 5-HT (serotonin) (By similarity). {ECO:0000250}. CC -!- SUBCELLULAR LOCATION: Cell membrane; Multi-pass membrane protein. CC Endosome. Note=Interaction with SNX27 mediates recruitment to early CC endosomes, while interaction with NHERF1 and EZR might target the CC protein to specialized subcellular regions, such as microvilli. CC {ECO:0000250}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=3; CC Comment=Additional isoforms seem to exist.; CC Name=5-HT4L; CC IsoId=Q62758-1; Sequence=Displayed; CC Name=5-HT4S; CC IsoId=Q62758-2; Sequence=VSP_001854; CC Name=5-HT4(E); CC IsoId=Q62758-3; Sequence=VSP_001855; CC -!- TISSUE SPECIFICITY: In brain, isoform 5-HT4S is restricted to the CC striatum, but isoform 5-HT4L is expressed throughout the brain, except CC in the cerebellum. In peripheral tissues, differential expression is CC also observed in the atrium of the heart where only isoform 5-HT4S is CC detectable. CC -!- SIMILARITY: Belongs to the G-protein coupled receptor 1 family. 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; U20907; AAC52233.1; -; mRNA. DR EMBL; U20906; AAC52232.1; -; mRNA. DR EMBL; Z48153; CAA88170.1; -; mRNA. DR EMBL; AJ011370; CAA09599.1; -; mRNA. DR PIR; S55549; S55549. DR PIR; S55550; S55550. DR RefSeq; NP_036985.1; NM_012853.1. DR AlphaFoldDB; Q62758; -. DR SMR; Q62758; -. DR STRING; 10116.ENSRNOP00000025892; -. DR BindingDB; Q62758; -. DR ChEMBL; CHEMBL4317; -. DR DrugCentral; Q62758; -. DR GuidetoPHARMACOLOGY; 9; -. DR GlyCosmos; Q62758; 1 site, No reported glycans. DR GlyGen; Q62758; 1 site. DR PhosphoSitePlus; Q62758; -. DR PaxDb; 10116-ENSRNOP00000025892; -. DR GeneID; 25324; -. DR KEGG; rno:25324; -. DR UCSC; RGD:2850; rat. [Q62758-1] DR AGR; RGD:2850; -. DR CTD; 3360; -. DR RGD; 2850; Htr4. DR eggNOG; KOG3656; Eukaryota. DR InParanoid; Q62758; -. DR PhylomeDB; Q62758; -. DR Reactome; R-RNO-390666; Serotonin receptors. DR PRO; PR:Q62758; -. DR Proteomes; UP000002494; Unplaced. DR GO; GO:0005737; C:cytoplasm; ISO:RGD. DR GO; GO:0030425; C:dendrite; IBA:GO_Central. DR GO; GO:0005768; C:endosome; IEA:UniProtKB-SubCell. DR GO; GO:0016020; C:membrane; ISO:RGD. DR GO; GO:0005886; C:plasma membrane; ISO:RGD. DR GO; GO:0045202; C:synapse; IEA:GOC. DR GO; GO:0004993; F:G protein-coupled serotonin receptor activity; IMP:RGD. DR GO; GO:0030594; F:neurotransmitter receptor activity; IBA:GO_Central. DR GO; GO:0099589; F:serotonin receptor activity; ISO:RGD. DR GO; GO:0007189; P:adenylate cyclase-activating G protein-coupled receptor signaling pathway; IMP:RGD. DR GO; GO:0007268; P:chemical synaptic transmission; IBA:GO_Central. DR GO; GO:0050890; P:cognition; TAS:RGD. DR GO; GO:0007186; P:G protein-coupled receptor signaling pathway; ISO:RGD. DR GO; GO:0007187; P:G protein-coupled receptor signaling pathway, coupled to cyclic nucleotide second messenger; IBA:GO_Central. DR GO; GO:0007214; P:gamma-aminobutyric acid signaling pathway; IMP:RGD. DR GO; GO:0120056; P:large intestinal transit; ISO:RGD. DR GO; GO:0030277; P:maintenance of gastrointestinal epithelium; ISO:RGD. DR GO; GO:0070254; P:mucus secretion; ISO:RGD. DR GO; GO:0032098; P:regulation of appetite; IEA:InterPro. DR CDD; cd15056; 7tmA_5-HT4; 1. DR Gene3D; 1.20.1070.10; Rhodopsin 7-helix transmembrane proteins; 1. DR InterPro; IPR001520; 5HT4_rcpt. DR InterPro; IPR000276; GPCR_Rhodpsn. DR InterPro; IPR017452; GPCR_Rhodpsn_7TM. DR PANTHER; PTHR24248:SF169; 5-HYDROXYTRYPTAMINE RECEPTOR 4; 1. DR PANTHER; PTHR24248; ADRENERGIC RECEPTOR-RELATED G-PROTEIN COUPLED RECEPTOR; 1. DR Pfam; PF00001; 7tm_1; 1. DR PRINTS; PR01059; 5HT4RECEPTR. DR PRINTS; PR00237; GPCRRHODOPSN. 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. PE 2: Evidence at transcript level; KW Alternative splicing; Cell membrane; Disulfide bond; Endosome; KW G-protein coupled receptor; Glycoprotein; Lipoprotein; Membrane; Palmitate; KW Receptor; Reference proteome; Transducer; Transmembrane; KW Transmembrane helix. FT CHAIN 1..406 FT /note="5-hydroxytryptamine receptor 4" FT /id="PRO_0000068968" FT TOPO_DOM 1..19 FT /note="Extracellular" FT /evidence="ECO:0000250" FT TRANSMEM 20..40 FT /note="Helical; Name=1" FT /evidence="ECO:0000250" FT TOPO_DOM 41..58 FT /note="Cytoplasmic" FT /evidence="ECO:0000250" FT TRANSMEM 59..79 FT /note="Helical; Name=2" FT /evidence="ECO:0000250" FT TOPO_DOM 80..93 FT /note="Extracellular" FT /evidence="ECO:0000250" FT TRANSMEM 94..116 FT /note="Helical; Name=3" FT /evidence="ECO:0000250" FT TOPO_DOM 117..137 FT /note="Cytoplasmic" FT /evidence="ECO:0000250" FT TRANSMEM 138..158 FT /note="Helical; Name=4" FT /evidence="ECO:0000250" FT TOPO_DOM 159..192 FT /note="Extracellular" FT /evidence="ECO:0000250" FT TRANSMEM 193..213 FT /note="Helical; Name=5" FT /evidence="ECO:0000250" FT TOPO_DOM 214..260 FT /note="Cytoplasmic" FT /evidence="ECO:0000250" FT TRANSMEM 261..281 FT /note="Helical; Name=6" FT /evidence="ECO:0000250" FT TOPO_DOM 282..294 FT /note="Extracellular" FT /evidence="ECO:0000250" FT TRANSMEM 295..315 FT /note="Helical; Name=7" FT /evidence="ECO:0000250" FT TOPO_DOM 316..406 FT /note="Cytoplasmic" FT /evidence="ECO:0000250" FT LIPID 329 FT /note="S-palmitoyl cysteine" FT /evidence="ECO:0000250" FT CARBOHYD 7 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT DISULFID 93..184 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00521" FT VAR_SEQ 359..406 FT /note="RDTVECGGQWESRCHLTATSPLVAAQPVIRRPQDNDLEDSCSLKRSQS -> FT SFPLLFCNRPVPV (in isoform 5-HT4(E))" FT /evidence="ECO:0000305" FT /id="VSP_001855" FT VAR_SEQ 360..406 FT /note="DTVECGGQWESRCHLTATSPLVAAQPVIRRPQDNDLEDSCSLKRSQS -> Y FT TVLHSGQHQELEKLPIHNDPESLESCF (in isoform 5-HT4S)" FT /evidence="ECO:0000305" FT /id="VSP_001854" FT CONFLICT 74..75 FT /note="NA -> MP (in Ref. 3; CAA09599)" FT /evidence="ECO:0000305" SQ SEQUENCE 406 AA; 46107 MW; A1889155A08930B4 CRC64; MDRLDANVSS NEGFGSVEKV VLLTFFAMVI LMAILGNLLV MVAVCRDRQL RKIKTNYFIV SLAFADLLVS VLVNAFGAIE LVQDIWFYGE MFCLVRTSLD VLLTTASIFH LCCISLDRYY AICCQPLVYR NKMTPLRIAL MLGGCWVIPM FISFLPIMQG WNNIGIVDVI EKRKFNHNSN STFCVFMVNK PYAITCSVVA FYIPFLLMVL AYYRIYVTAK EHAQQIQMLQ RAGATSESRP QTADQHSTHR MRTETKAAKT LCVIMGCFCF CWAPFFVTNI VDPFIDYTVP EKVWTAFLWL GYINSGLNPF LYAFLNKSFR RAFLIILCCD DERYKRPPIL GQTVPCSTTT INGSTHVLRD TVECGGQWES RCHLTATSPL VAAQPVIRRP QDNDLEDSCS LKRSQS //