ID 5HT4R_HUMAN Reviewed; 388 AA. AC Q13639; Q96KH9; Q96KI0; Q9H199; Q9NY73; Q9UBM6; Q9UBT4; Q9UE22; AC Q9UE23; Q9UQR6; DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot. DT 11-JAN-2001, sequence version 2. DT 19-JAN-2010, entry version 95. 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 Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; OC Catarrhini; Hominidae; Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 5-HT4(A); 5-HT4(B); 5-HT4(C) AND RP 5-HT4(D)). RC TISSUE=Gut; RX MEDLINE=98264328; PubMed=9603189; RA Blondel O., Gastineau M., Dahmoune Y., Langlois M., Fischmeister R.; RT "Cloning, expression, and pharmacology of four human 5- RT hydroxytryptamine 4 receptor isoforms produced by alternative splicing RT in the carboxyl terminus."; RL J. Neurochem. 70:2252-2261(1998). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 5-HT4(A) AND 5-HT4(B)). RC TISSUE=Brain; RA Van den Wyngaert I., Gommeren W., Jurzak M., Verhasselt P., Gordon R., RA Leysen J., Luyten W., Bender E.; RT "Cloning and expression of 5-HT4 receptor species and splice RT variants."; RL Submitted (JUN-1997) to the EMBL/GenBank/DDBJ databases. RN [3] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 5-HT4(A)). RC TISSUE=Heart; RX MEDLINE=98012006; PubMed=9351641; RA Claeysen S., Faye P., Sebben M., Lemaire S., Bockaert J., Dumuis A.; RT "Cloning and expression of human 5-HT4S receptors. Effect of receptor RT density on their coupling to adenylyl cyclase."; RL NeuroReport 8:3189-3195(1997). RN [4] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 5-HT4(E)). RC TISSUE=Brain; RX MEDLINE=99238795; 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). RN [5] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 5-HT4(A); 5-HT4(E) AND 5-HT4(G)). RC TISSUE=Hippocampus; RA Vilaro M.T., Domenech T., Palacios J.M., Mengod G.; RT "Cloning and characterization of multiple human 5-HT4 receptor RT variants including a novel variant that lacks the alternatively RT spliced C-terminal exon."; RL Submitted (SEP-2000) to the EMBL/GenBank/DDBJ databases. RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 5-HT4(B)). 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 RT project: the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [7] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 10-388 (ISOFORM 5-HT4(F)). RX MEDLINE=20110418; PubMed=10646498; RX DOI=10.1046/j.1471-4159.2000.740478.x; RA Bender E., Pindon A., van Oers I., Zhang Y.B., Gommeren W., RA Verhasselt P., Jurzak M., Leysen J., Luyten W.; RT "Structure of the human serotonin 5-HT4 receptor gene and cloning of a RT novel 5-HT4 splice variant."; RL J. Neurochem. 74:478-489(2000). RN [8] RP NUCLEOTIDE SEQUENCE [MRNA] OF 112-255. RC TISSUE=Brain; RX MEDLINE=95385798; 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). CC -!- FUNCTION: This is one of the several different receptors for 5- CC hydroxytryptamine (serotonin), a biogenic hormone that functions CC as a neurotransmitter, a hormone, and a mitogen. The activity of CC this receptor is mediated by G proteins that stimulate adenylate CC cyclase. CC -!- SUBUNIT: Isoform 5-HT4(A) interacts with MAGI2, MPP3, SLC9A3R1 and CC SNX27 isoforms 1 and 2. Isoform 5-HT4(E) interacts with INADL, CC NOS1 and SEC23A. Isoform 5-HT4(A) forms a complex including CC SLC9A3R1 and EZR (By similarity). CC -!- SUBCELLULAR LOCATION: Cell membrane; Multi-pass membrane protein. CC Endosome. Note=Interaction with SNX27 mediates recruitment to CC early endosomes, while interaction with SLC9A3R1 and EZR might CC target the protein to specialized subcellular regions, such as CC microvilli (By similarity). CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=7; CC Comment=Additional isoforms seem to exist; CC Name=5-HT4(B); CC IsoId=Q13639-1; Sequence=Displayed; CC Name=5-HT4(A); Synonyms=5-HT4S; CC IsoId=Q13639-2; Sequence=VSP_001849; CC Name=5-HT4(C); CC IsoId=Q13639-3; Sequence=VSP_001848; CC Name=5-HT4(D); CC IsoId=Q13639-4; Sequence=VSP_001847; CC Name=5-HT4(E); Synonyms=H5-HT4(g); CC IsoId=Q13639-5; Sequence=VSP_001846; CC Name=5-HT4(F); CC IsoId=Q13639-6; Sequence=VSP_001845; CC Name=5-HT4(G); CC IsoId=Q13639-7; Sequence=VSP_001850; CC -!- TISSUE SPECIFICITY: Isoform 5-HT4(A) is expressed in ileum, brain, CC and atrium, but not in the ventricle. CC -!- SIMILARITY: Belongs to the G-protein coupled receptor 1 family. CC ----------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution-NoDerivs License CC ----------------------------------------------------------------------- DR EMBL; Y08756; CAA70002.1; -; mRNA. DR EMBL; Y12505; CAA73107.1; -; mRNA. DR EMBL; Y12506; CAA73108.1; -; mRNA. DR EMBL; Y12507; CAA73109.1; -; mRNA. DR EMBL; Y10437; CAA71462.1; -; mRNA. DR EMBL; Y13584; CAA73911.1; -; mRNA. DR EMBL; Y09586; CAA70774.1; -; mRNA. DR EMBL; AJ011371; CAA09600.1; -; mRNA. DR EMBL; AJ278979; CAC22248.1; -; mRNA. DR EMBL; AJ278981; CAC22250.1; -; mRNA. DR EMBL; AJ278982; CAC22251.1; -; mRNA. DR EMBL; BC074755; AAH74755.1; -; mRNA. DR EMBL; AJ243213; CAB71316.1; -; Genomic_DNA. DR EMBL; Z48150; CAA88167.1; -; mRNA. DR IPI; IPI00014378; -. DR IPI; IPI00064638; -. DR IPI; IPI00186777; -. DR IPI; IPI00216427; -. DR IPI; IPI00216428; -. DR IPI; IPI00216429; -. DR IPI; IPI00291659; -. DR PIR; S66493; S66493. DR RefSeq; NP_000861.1; -. DR RefSeq; NP_001035259.1; -. DR RefSeq; NP_001035261.1; -. DR RefSeq; NP_001035264.1; -. DR RefSeq; NP_955525.1; -. DR UniGene; Hs.483773; -. DR SMR; Q13639; 18-329. DR STRING; Q13639; -. DR Ensembl; ENST00000377888; ENSP00000367120; ENSG00000164270; Homo sapiens. DR GeneID; 3360; -. DR KEGG; hsa:3360; -. DR UCSC; uc003lpj.1; human. DR UCSC; uc003lpk.1; human. DR UCSC; uc003lpl.1; human. DR UCSC; uc003lpn.1; human. DR UCSC; uc003lpo.1; human. DR CTD; 3360; -. DR GeneCards; GC05M147810; -. DR H-InvDB; HIX0005295; -. DR H-InvDB; HIX0078165; -. DR HGNC; HGNC:5299; HTR4. DR MIM; 602164; gene. DR PharmGKB; PA29557; -. DR eggNOG; prNOG13487; -. DR HOVERGEN; Q13639; -. DR Reactome; REACT_14797; Signaling by GPCR. DR DrugBank; DB00604; Cisapride. DR DrugBank; DB00953; Rizatriptan. DR DrugBank; DB01079; Tegaserod. DR DrugBank; DB00315; Zolmitriptan. DR NextBio; 13288; -. DR ArrayExpress; Q13639; -. DR Bgee; Q13639; -. DR Genevestigator; Q13639; -. DR GermOnline; ENSG00000164270; Homo sapiens. DR GO; GO:0005768; C:endosome; IEA:UniProtKB-SubCell. DR GO; GO:0005887; C:integral to plasma membrane; TAS:ProtInc. DR GO; GO:0005624; C:membrane fraction; IDA:MGI. DR GO; GO:0004993; F:serotonin receptor activity; IDA:MGI. DR GO; GO:0007187; P:G-protein signaling, coupled to cyclic nucl...; TAS:ProtInc. DR InterPro; IPR001520; 5HT4_rcpt. DR InterPro; IPR000276; 7TM_GPCR_Rhodpsn. DR InterPro; IPR017452; GPCR_Rhodpsn_supfam. DR Pfam; PF00001; 7tm_1; 1. DR PRINTS; PR01059; 5HT4RECEPTR. DR PRINTS; PR00237; GPCRRHODOPSN. 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; Complete proteome; KW Disulfide bond; Endosome; G-protein coupled receptor; Glycoprotein; KW Lipoprotein; Membrane; Palmitate; Polymorphism; Receptor; Transducer; KW Transmembrane. FT CHAIN 1 388 5-hydroxytryptamine receptor 4. FT /FTId=PRO_0000068965. FT TOPO_DOM 1 19 Extracellular (By similarity). FT TRANSMEM 20 40 1 (By similarity). FT TOPO_DOM 41 58 Cytoplasmic (By similarity). FT TRANSMEM 59 79 2 (By similarity). FT TOPO_DOM 80 93 Extracellular (By similarity). FT TRANSMEM 94 116 3 (By similarity). FT TOPO_DOM 117 137 Cytoplasmic (By similarity). FT TRANSMEM 138 158 4 (By similarity). FT TOPO_DOM 159 192 Extracellular (By similarity). FT TRANSMEM 193 213 5 (By similarity). FT TOPO_DOM 214 260 Cytoplasmic (By similarity). FT TRANSMEM 261 281 6 (By similarity). FT TOPO_DOM 282 294 Extracellular (By similarity). FT TRANSMEM 295 315 7 (By similarity). FT TOPO_DOM 316 388 Cytoplasmic (By similarity). FT LIPID 329 329 S-palmitoyl cysteine (By similarity). FT CARBOHYD 7 7 N-linked (GlcNAc...) (Potential). FT DISULFID 93 184 By similarity. FT VAR_SEQ 169 169 L -> LERSLNQGLGQDFHA (in isoform 5- FT HT4(F)). FT /FTId=VSP_001845. FT VAR_SEQ 359 388 RDAVECGGQWESQCHPPATSPLVAAQPSDT -> SSGTETD FT RRNFGIRKRRLTKPS (in isoform 5-HT4(D)). FT /FTId=VSP_001847. FT VAR_SEQ 359 388 RDAVECGGQWESQCHPPATSPLVAAQPSDT -> SGCSPVS FT SFLLLFCNRPVPV (in isoform 5-HT4(E)). FT /FTId=VSP_001846. FT VAR_SEQ 360 388 DAVECGGQWESQCHPPATSPLVAAQPSDT -> YTVLHRGH FT HQELEKLPIHNDPESLESCF (in isoform 5- FT HT4(A)). FT /FTId=VSP_001849. FT VAR_SEQ 360 388 DAVECGGQWESQCHPPATSPLVAAQPSDT -> F (in FT isoform 5-HT4(C)). FT /FTId=VSP_001848. FT VAR_SEQ 360 388 Missing (in isoform 5-HT4(G)). FT /FTId=VSP_001850. FT VARIANT 372 372 C -> Y (in dbSNP:rs34826744). FT /FTId=VAR_049364. SQ SEQUENCE 388 AA; 43761 MW; 7FCFEC60E7BDF560 CRC64; MDKLDANVSS EEGFGSVEKV VLLTFLSTVI LMAILGNLLV MVAVCWDRQL RKIKTNYFIV SLAFADLLVS VLVMPFGAIE LVQDIWIYGE VFCLVRTSLD VLLTTASIFH LCCISLDRYY AICCQPLVYR NKMTPLRIAL MLGGCWVIPT FISFLPIMQG WNNIGIIDLI EKRKFNQNSN STYCVFMVNK PYAITCSVVA FYIPFLLMVL AYYRIYVTAK EHAHQIQMLQ RAGASSESRP QSADQHSTHR MRTETKAAKT LCIIMGCFCL CWAPFFVTNI VDPFIDYTVP GQVWTAFLWL GYINSGLNPF LYAFLNKSFR RAFLIILCCD DERYRRPSIL GQTVPCSTTT INGSTHVLRD AVECGGQWES QCHPPATSPL VAAQPSDT //