ID   5HT4R_HUMAN             Reviewed;         388 AA.
AC   Q13639; C4WYH4; Q546Q1; Q684M0; Q712M9; Q96KH9; Q96KI0; Q9H199; Q9NY73;
AC   Q9UBM6; Q9UBT4; Q9UE22; Q9UE23; Q9UQR6;
DT   01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT   11-JAN-2001, sequence version 2.
DT   24-JAN-2024, entry version 206.
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; Mammalia;
OC   Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC   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=Intestine;
RX   PubMed=9603189; DOI=10.1046/j.1471-4159.1998.70062252.x;
RA   Blondel O., Gastineau M., Dahmoune Y., Langlois M., Fischmeister R.;
RT   "Cloning, expression, and pharmacology of four human 5-hydroxytryptamine 4
RT   receptor isoforms produced by alternative splicing in the carboxyl
RT   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 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   PubMed=9351641; DOI=10.1097/00001756-199710200-00002;
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(B)).
RA   Syversveen T., Bach T., Kvingedal A.M., Krobert K.A., Kaumann A.J.,
RA   Levy F.O.;
RT   "Molecular cloning of the human serotonin receptor 5-HT4(b) and
RT   pharmacological comparison with the cloned human 5-HT4(a) receptor.";
RL   Submitted (DEC-1998) to the EMBL/GenBank/DDBJ databases.
RN   [5]
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).
RN   [6]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 5-HT4(A); 5-HT4(B); 5-HT4(E) AND
RP   5-HT4(G)).
RC   TISSUE=Brain, and Hippocampus;
RX   PubMed=11750916; DOI=10.1016/s0028-3908(01)00154-x;
RA   Vilaro M.T., Domenech T., Palacios J.M., Mengod G.;
RT   "Cloning and characterization of a novel human 5-HT4 receptor variant that
RT   lacks the alternatively spliced carboxy terminal exon. RT-PCR distribution
RT   in human brain and periphery of multiple 5-HT4 receptor variants.";
RL   Neuropharmacology 42:60-73(2002).
RN   [7]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 5-HT4(E) AND 5-HT4(I)), AND TISSUE
RP   SPECIFICITY.
RX   PubMed=15118808; DOI=10.1007/s00210-004-0919-4;
RA   Brattelid T., Kvingedal A.M., Krobert K.A., Andressen K.W., Bach T.,
RA   Hystad M.E., Kaumann A.J., Levy F.O.;
RT   "Cloning, pharmacological characterisation and tissue distribution of a
RT   novel 5-HT4 receptor splice variant, 5-HT4(i).";
RL   Naunyn Schmiedebergs Arch. Pharmacol. 369:616-628(2004).
RN   [8]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 5-HT4C1).
RC   TISSUE=Small intestine;
RA   Reid A.M., Kelsell R.E., Houp J.A., Kelly F.M., Medhurst A.D., Cox H.M.,
RA   Calver A.R.;
RT   "Cloning, expression and characterisation of a novel rat 5-HT4 receptor
RT   splice variant (5-HT4c1).";
RL   Submitted (MAY-2007) to the EMBL/GenBank/DDBJ databases.
RN   [9]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX   PubMed=15372022; DOI=10.1038/nature02919;
RA   Schmutz J., Martin J., Terry A., Couronne O., Grimwood J., Lowry S.,
RA   Gordon L.A., Scott D., Xie G., Huang W., Hellsten U., Tran-Gyamfi M.,
RA   She X., Prabhakar S., Aerts A., Altherr M., Bajorek E., Black S.,
RA   Branscomb E., Caoile C., Challacombe J.F., Chan Y.M., Denys M.,
RA   Detter J.C., Escobar J., Flowers D., Fotopulos D., Glavina T., Gomez M.,
RA   Gonzales E., Goodstein D., Grigoriev I., Groza M., Hammon N., Hawkins T.,
RA   Haydu L., Israni S., Jett J., Kadner K., Kimball H., Kobayashi A.,
RA   Lopez F., Lou Y., Martinez D., Medina C., Morgan J., Nandkeshwar R.,
RA   Noonan J.P., Pitluck S., Pollard M., Predki P., Priest J., Ramirez L.,
RA   Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A., Thayer N.,
RA   Tice H., Tsai M., Ustaszewska A., Vo N., Wheeler J., Wu K., Yang J.,
RA   Dickson M., Cheng J.-F., Eichler E.E., Olsen A., Pennacchio L.A.,
RA   Rokhsar D.S., Richardson P., Lucas S.M., Myers R.M., Rubin E.M.;
RT   "The DNA sequence and comparative analysis of human chromosome 5.";
RL   Nature 431:268-274(2004).
RN   [10]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA   Mural R.J., Istrail S., Sutton 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   [11]
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 project:
RT   the Mammalian Gene Collection (MGC).";
RL   Genome Res. 14:2121-2127(2004).
RN   [12]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 10-388 (ISOFORM 5-HT4(F)).
RX   PubMed=10646498; DOI=10.1046/j.1471-4159.2000.740478.x;
RA   Bender E., Pindon A., van Oers I., Zhang Y.B., Gommeren W., Verhasselt P.,
RA   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   [13]
RP   NUCLEOTIDE SEQUENCE [MRNA] OF 112-255.
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   [14]
RP   INTERACTION WITH GRK5, AND IDENTIFICATION BY MASS SPECTROMETRY.
RX   PubMed=19661922; DOI=10.1038/emboj.2009.215;
RA   Barthet G., Carrat G., Cassier E., Barker B., Gaven F., Pillot M.,
RA   Framery B., Pellissier L.P., Augier J., Kang D.S., Claeysen S., Reiter E.,
RA   Baneres J.L., Benovic J.L., Marin P., Bockaert J., Dumuis A.;
RT   "Beta-arrestin1 phosphorylation by GRK5 regulates G protein-independent 5-
RT   HT4 receptor signalling.";
RL   EMBO J. 28:2706-2718(2009).
RN   [15]
RP   VARIANT LEU-27.
RX   PubMed=22197934; DOI=10.1038/ng.1027;
RA   Rademakers R., Baker M., Nicholson A.M., Rutherford N.J., Finch N.,
RA   Soto-Ortolaza A., Lash J., Wider C., Wojtas A., DeJesus-Hernandez M.,
RA   Adamson J., Kouri N., Sundal C., Shuster E.A., Aasly J., MacKenzie J.,
RA   Roeber S., Kretzschmar H.A., Boeve B.F., Knopman D.S., Petersen R.C.,
RA   Cairns N.J., Ghetti B., Spina S., Garbern J., Tselis A.C., Uitti R.,
RA   Das P., Van Gerpen J.A., Meschia J.F., Levy S., Broderick D.F.,
RA   Graff-Radford N., Ross O.A., Miller B.B., Swerdlow R.H., Dickson D.W.,
RA   Wszolek Z.K.;
RT   "Mutations in the colony stimulating factor 1 receptor (CSF1R) gene cause
RT   hereditary diffuse leukoencephalopathy with spheroids.";
RL   Nat. Genet. 44:200-205(2012).
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: Isoform 5-HT4(A) interacts with MAGI2, MPP3, NHERF1 and SNX27
CC       isoforms 1 and 2. Isoform 5-HT4(E) interacts with PATJ, NOS1 and
CC       SEC23A. Isoform 5-HT4(A) forms a complex including NHERF1 and EZR (By
CC       similarity). Interacts (via C-terminus 330-346 AA) with GRK5; this
CC       interaction is promoted by 5-HT (serotonin). {ECO:0000250,
CC       ECO:0000269|PubMed:19661922}.
CC   -!- INTERACTION:
CC       Q13639; O15354: GPR37; NbExp=5; IntAct=EBI-6656425, EBI-15639515;
CC       Q13639; O60269: GPRIN2; NbExp=2; IntAct=EBI-6656425, EBI-740397;
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=9;
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       Name=5-HT4(I);
CC         IsoId=Q13639-8; Sequence=VSP_043316;
CC       Name=5-HT4c1;
CC         IsoId=Q13639-9; Sequence=VSP_047862;
CC   -!- TISSUE SPECIFICITY: Isoform 5-HT4(A) is expressed in ileum, brain, and
CC       atrium, but not in the ventricle. {ECO:0000269|PubMed:15118808}.
CC   -!- MISCELLANEOUS: [Isoform 5-HT4(E)]: Mainly expressed in atria and
CC       cardiac ventricle. {ECO:0000305}.
CC   -!- MISCELLANEOUS: [Isoform 5-HT4(I)]: Expressed in all cardiovascular
CC       tissues analyzed. {ECO:0000305}.
CC   -!- SIMILARITY: Belongs to the G-protein coupled receptor 1 family.
CC       {ECO:0000255|PROSITE-ProRule:PRU00521}.
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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; AJ131724; CAC20411.1; -; mRNA.
DR   EMBL; AJ011371; CAA09600.1; -; mRNA.
DR   EMBL; AJ278979; CAC22248.1; -; mRNA.
DR   EMBL; AJ278980; CAC22249.1; -; mRNA.
DR   EMBL; AJ278981; CAC22250.1; -; mRNA.
DR   EMBL; AJ278982; CAC22251.1; -; mRNA.
DR   EMBL; AJ131725; CAC79533.1; -; mRNA.
DR   EMBL; AJ131726; CAC79538.1; -; mRNA.
DR   EMBL; AJ633645; CAG17627.1; -; mRNA.
DR   EMBL; AM712912; CAN84676.1; -; mRNA.
DR   EMBL; AC008627; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; AC011390; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; AC091971; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; AC114939; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; CH471062; EAW61800.1; -; Genomic_DNA.
DR   EMBL; CH471062; EAW61801.1; -; Genomic_DNA.
DR   EMBL; CH471062; EAW61804.1; -; Genomic_DNA.
DR   EMBL; BC074755; AAH74755.1; -; mRNA.
DR   EMBL; BC095497; AAH95497.1; -; mRNA.
DR   EMBL; AJ243213; CAB71316.1; -; Genomic_DNA.
DR   EMBL; Z48150; CAA88167.1; -; mRNA.
DR   CCDS; CCDS34270.1; -. [Q13639-2]
DR   CCDS; CCDS34271.1; -. [Q13639-5]
DR   CCDS; CCDS34272.1; -. [Q13639-8]
DR   CCDS; CCDS34273.2; -. [Q13639-3]
DR   CCDS; CCDS4291.1; -. [Q13639-1]
DR   CCDS; CCDS75353.1; -. [Q13639-9]
DR   PIR; S66493; S66493.
DR   RefSeq; NP_000861.1; NM_000870.6. [Q13639-1]
DR   RefSeq; NP_001035259.1; NM_001040169.2. [Q13639-2]
DR   RefSeq; NP_001035262.2; NM_001040172.2. [Q13639-3]
DR   RefSeq; NP_001035263.1; NM_001040173.2. [Q13639-8]
DR   RefSeq; NP_001273339.1; NM_001286410.1. [Q13639-9]
DR   RefSeq; NP_955525.1; NM_199453.3. [Q13639-5]
DR   PDB; 5EM9; X-ray; 1.60 A; B=264-268.
DR   PDB; 7XT8; EM; 3.10 A; R=2-388.
DR   PDB; 7XT9; EM; 3.20 A; R=2-388.
DR   PDB; 7XTA; EM; 3.20 A; R=2-388.
DR   PDBsum; 5EM9; -.
DR   PDBsum; 7XT8; -.
DR   PDBsum; 7XT9; -.
DR   PDBsum; 7XTA; -.
DR   AlphaFoldDB; Q13639; -.
DR   SMR; Q13639; -.
DR   BioGRID; 109592; 17.
DR   IntAct; Q13639; 17.
DR   MINT; Q13639; -.
DR   STRING; 9606.ENSP00000353915; -.
DR   BindingDB; Q13639; -.
DR   ChEMBL; CHEMBL1875; -.
DR   DrugBank; DB01239; Chlorprothixene.
DR   DrugBank; DB08810; Cinitapride.
DR   DrugBank; DB00604; Cisapride.
DR   DrugBank; DB11273; Dihydroergocornine.
DR   DrugBank; DB13345; Dihydroergocristine.
DR   DrugBank; DB00320; Dihydroergotamine.
DR   DrugBank; DB01049; Ergoloid mesylate.
DR   DrugBank; DB12141; Gilteritinib.
DR   DrugBank; DB01233; Metoclopramide.
DR   DrugBank; DB05542; Naronapride.
DR   DrugBank; DB00904; Ondansetron.
DR   DrugBank; DB00715; Paroxetine.
DR   DrugBank; DB04873; Piboserod.
DR   DrugBank; DB06480; Prucalopride.
DR   DrugBank; DB04917; Renzapride.
DR   DrugBank; DB09304; Setiptiline.
DR   DrugBank; DB05905; TD-2749.
DR   DrugBank; DB01079; Tegaserod.
DR   DrugBank; DB13025; Tiapride.
DR   DrugBank; DB06422; Ticalopride.
DR   DrugBank; DB12702; Velusetrag.
DR   DrugCentral; Q13639; -.
DR   GuidetoPHARMACOLOGY; 9; -.
DR   TCDB; 9.A.14.3.18; the g-protein-coupled receptor (gpcr) family.
DR   GlyCosmos; Q13639; 1 site, No reported glycans.
DR   GlyGen; Q13639; 1 site.
DR   iPTMnet; Q13639; -.
DR   PhosphoSitePlus; Q13639; -.
DR   SwissPalm; Q13639; -.
DR   BioMuta; HTR4; -.
DR   DMDM; 12644029; -.
DR   MassIVE; Q13639; -.
DR   PaxDb; 9606-ENSP00000353915; -.
DR   PeptideAtlas; Q13639; -.
DR   Antibodypedia; 15936; 494 antibodies from 33 providers.
DR   DNASU; 3360; -.
DR   Ensembl; ENST00000360693.7; ENSP00000353915.3; ENSG00000164270.19. [Q13639-8]
DR   Ensembl; ENST00000377888.8; ENSP00000367120.4; ENSG00000164270.19. [Q13639-1]
DR   Ensembl; ENST00000517929.5; ENSP00000435904.1; ENSG00000164270.19. [Q13639-3]
DR   Ensembl; ENST00000520514.5; ENSP00000427913.1; ENSG00000164270.19. [Q13639-9]
DR   Ensembl; ENST00000521530.6; ENSP00000428320.1; ENSG00000164270.19. [Q13639-2]
DR   Ensembl; ENST00000521735.5; ENSP00000430979.1; ENSG00000164270.19. [Q13639-5]
DR   Ensembl; ENST00000522588.5; ENSP00000430874.1; ENSG00000164270.19. [Q13639-5]
DR   GeneID; 3360; -.
DR   KEGG; hsa:3360; -.
DR   MANE-Select; ENST00000377888.8; ENSP00000367120.4; NM_000870.7; NP_000861.1.
DR   UCSC; uc003lpn.5; human. [Q13639-1]
DR   AGR; HGNC:5299; -.
DR   CTD; 3360; -.
DR   DisGeNET; 3360; -.
DR   GeneCards; HTR4; -.
DR   HGNC; HGNC:5299; HTR4.
DR   HPA; ENSG00000164270; Group enriched (brain, heart muscle, intestine).
DR   MIM; 602164; gene.
DR   neXtProt; NX_Q13639; -.
DR   OpenTargets; ENSG00000164270; -.
DR   PharmGKB; PA29557; -.
DR   VEuPathDB; HostDB:ENSG00000164270; -.
DR   eggNOG; KOG3656; Eukaryota.
DR   GeneTree; ENSGT00940000155983; -.
DR   HOGENOM; CLU_009579_11_0_1; -.
DR   InParanoid; Q13639; -.
DR   OMA; NTHRMRT; -.
DR   OrthoDB; 2908467at2759; -.
DR   PhylomeDB; Q13639; -.
DR   TreeFam; TF316350; -.
DR   PathwayCommons; Q13639; -.
DR   Reactome; R-HSA-390666; Serotonin receptors.
DR   Reactome; R-HSA-418555; G alpha (s) signalling events.
DR   SignaLink; Q13639; -.
DR   SIGNOR; Q13639; -.
DR   BioGRID-ORCS; 3360; 12 hits in 1153 CRISPR screens.
DR   ChiTaRS; HTR4; human.
DR   GeneWiki; 5-HT4_receptor; -.
DR   GenomeRNAi; 3360; -.
DR   Pharos; Q13639; Tclin.
DR   PRO; PR:Q13639; -.
DR   Proteomes; UP000005640; Chromosome 5.
DR   RNAct; Q13639; Protein.
DR   Bgee; ENSG00000164270; Expressed in type B pancreatic cell and 181 other cell types or tissues.
DR   ExpressionAtlas; Q13639; baseline and differential.
DR   GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR   GO; GO:0030425; C:dendrite; IBA:GO_Central.
DR   GO; GO:0005768; C:endosome; IEA:UniProtKB-SubCell.
DR   GO; GO:0016020; C:membrane; IDA:MGI.
DR   GO; GO:0005886; C:plasma membrane; TAS:Reactome.
DR   GO; GO:0045202; C:synapse; IEA:GOC.
DR   GO; GO:0004993; F:G protein-coupled serotonin receptor activity; IDA:MGI.
DR   GO; GO:0030594; F:neurotransmitter receptor activity; IBA:GO_Central.
DR   GO; GO:0099589; F:serotonin receptor activity; IDA:UniProt.
DR   GO; GO:0007268; P:chemical synaptic transmission; IBA:GO_Central.
DR   GO; GO:0007186; P:G protein-coupled 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:0120056; P:large intestinal transit; IDA:UniProt.
DR   GO; GO:0030277; P:maintenance of gastrointestinal epithelium; IEA:Ensembl.
DR   GO; GO:0070254; P:mucus secretion; IEA:Ensembl.
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.
DR   Genevisible; Q13639; HS.
PE   1: Evidence at protein level;
KW   3D-structure; Alternative splicing; Cell membrane; Disulfide bond;
KW   Endosome; G-protein coupled receptor; Glycoprotein; Lipoprotein; Membrane;
KW   Palmitate; Receptor; Reference proteome; Transducer; Transmembrane;
KW   Transmembrane helix.
FT   CHAIN           1..388
FT                   /note="5-hydroxytryptamine receptor 4"
FT                   /id="PRO_0000068965"
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..388
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         169
FT                   /note="L -> LERSLNQGLGQDFHA (in isoform 5-HT4(F))"
FT                   /evidence="ECO:0000305"
FT                   /id="VSP_001845"
FT   VAR_SEQ         359..388
FT                   /note="RDAVECGGQWESQCHPPATSPLVAAQPSDT -> SSGTETDRRNFGIRKRRL
FT                   TKPS (in isoform 5-HT4(D))"
FT                   /evidence="ECO:0000305"
FT                   /id="VSP_001847"
FT   VAR_SEQ         359..388
FT                   /note="RDAVECGGQWESQCHPPATSPLVAAQPSDT -> SGCSPVSSFLLLFCNRPV
FT                   PV (in isoform 5-HT4(E))"
FT                   /evidence="ECO:0000305"
FT                   /id="VSP_001846"
FT   VAR_SEQ         359..388
FT                   /note="RDAVECGGQWESQCHPPATSPLVAAQPSDT -> SSGTETDRKKLWNKEEKI
FT                   DQTIQMPKRKRKKKASLSYEDLILLGRKSCFREGK (in isoform 5-HT4c1)"
FT                   /evidence="ECO:0000303|Ref.8"
FT                   /id="VSP_047862"
FT   VAR_SEQ         359
FT                   /note="R -> RTDFLFDRDILARYWTKPARAGPFSGTLSIRCLTARKPVLG (in
FT                   isoform 5-HT4(I))"
FT                   /evidence="ECO:0000305"
FT                   /id="VSP_043316"
FT   VAR_SEQ         360..388
FT                   /note="DAVECGGQWESQCHPPATSPLVAAQPSDT -> YTVLHRGHHQELEKLPIHN
FT                   DPESLESCF (in isoform 5-HT4(A))"
FT                   /evidence="ECO:0000305"
FT                   /id="VSP_001849"
FT   VAR_SEQ         360..388
FT                   /note="DAVECGGQWESQCHPPATSPLVAAQPSDT -> F (in isoform
FT                   5-HT4(C))"
FT                   /evidence="ECO:0000305"
FT                   /id="VSP_001848"
FT   VAR_SEQ         360..388
FT                   /note="Missing (in isoform 5-HT4(G))"
FT                   /evidence="ECO:0000305"
FT                   /id="VSP_001850"
FT   VARIANT         27
FT                   /note="S -> L (in a patient with diffuse
FT                   leukoencephalopathy with spheroids; uncertain significance;
FT                   dbSNP:rs199508638)"
FT                   /evidence="ECO:0000269|PubMed:22197934"
FT                   /id="VAR_067412"
FT   VARIANT         372
FT                   /note="C -> Y (in dbSNP:rs34826744)"
FT                   /id="VAR_049364"
FT   HELIX           22..46
FT                   /evidence="ECO:0007829|PDB:7XT8"
FT   HELIX           48..51
FT                   /evidence="ECO:0007829|PDB:7XT8"
FT   HELIX           55..72
FT                   /evidence="ECO:0007829|PDB:7XT8"
FT   HELIX           74..83
FT                   /evidence="ECO:0007829|PDB:7XT8"
FT   HELIX           89..123
FT                   /evidence="ECO:0007829|PDB:7XT8"
FT   HELIX           126..128
FT                   /evidence="ECO:0007829|PDB:7XT9"
FT   HELIX           129..132
FT                   /evidence="ECO:0007829|PDB:7XT8"
FT   HELIX           135..158
FT                   /evidence="ECO:0007829|PDB:7XT8"
FT   TURN            159..165
FT                   /evidence="ECO:0007829|PDB:7XT8"
FT   HELIX           167..174
FT                   /evidence="ECO:0007829|PDB:7XT8"
FT   HELIX           190..200
FT                   /evidence="ECO:0007829|PDB:7XT8"
FT   HELIX           202..232
FT                   /evidence="ECO:0007829|PDB:7XT8"
FT   HELIX           255..284
FT                   /evidence="ECO:0007829|PDB:7XT8"
FT   TURN            285..287
FT                   /evidence="ECO:0007829|PDB:7XT8"
FT   HELIX           291..312
FT                   /evidence="ECO:0007829|PDB:7XT8"
FT   TURN            313..315
FT                   /evidence="ECO:0007829|PDB:7XT8"
FT   HELIX           317..328
FT                   /evidence="ECO:0007829|PDB:7XT8"
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
//