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.
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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; 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
//
