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5-hydroxytryptamine receptor 4 (5-HT-4) (5-HT4) (Serotonin receptor 4)

 5HT4R_RAT               Reviewed;         406 AA.
Q62758; O89034; Q62757; Q63006;
01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
01-NOV-1996, sequence version 1.
23-MAY-2018, entry version 140.
RecName: Full=5-hydroxytryptamine receptor 4;
Short=5-HT-4;
Short=5-HT4;
AltName: Full=Serotonin receptor 4;
Name=Htr4;
Rattus norvegicus (Rat).
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha;
Muroidea; Muridae; Murinae; Rattus.
NCBI_TaxID=10116;
[1]
NUCLEOTIDE SEQUENCE [MRNA].
TISSUE=Brain;
PubMed=7796807;
Gerald C., Adham N., Kao H.T., Olsen M.A., Laz T.M., Schechter L.E.,
Bard J.A., Vaysse P., Hartig P.R., Branchek T.A., Weinshank R.L.;
"The 5-HT4 receptor: molecular cloning and pharmacological
characterization of two splice variants.";
EMBO J. 14:2806-2815(1995).
[2]
NUCLEOTIDE SEQUENCE [MRNA] OF 165-259.
TISSUE=Brain;
PubMed=7656980; DOI=10.1016/0014-5793(95)00828-W;
Ullmer C., Schmuck K., Kalkman H.O., Luebbert H.;
"Expression of serotonin receptor mRNAs in blood vessels.";
FEBS Lett. 370:215-221(1995).
[3]
NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 5-HT4(E)).
TISSUE=Brain;
PubMed=10220570;
Claeysen S., Sebben M., Becamel C., Bockaert J., Dumuis A.;
"Novel brain-specific 5-HT4 receptor splice variants show marked
constitutive activity: role of the C-terminal intracellular domain.";
Mol. Pharmacol. 55:910-920(1999).
-!- FUNCTION: This is one of the several different receptors for 5-
hydroxytryptamine (serotonin), a biogenic hormone that functions
as a neurotransmitter, a hormone, and a mitogen. The activity of
this receptor is mediated by G proteins that stimulate adenylate
cyclase.
-!- SUBUNIT: May interact with PATJ, MAGI2, MPP3, NOS1, SLC9A3R1,
SEC23A and SNX27. May form a complex including SLC9A3R1 and EZR
(By similarity). Interacts (via C-terminus 330-346 AA) with GRK5;
this interaction is promoted by 5-HT (serotonin) (By similarity).
{ECO:0000250}.
-!- SUBCELLULAR LOCATION: Cell membrane; Multi-pass membrane protein.
Endosome. Note=Interaction with SNX27 mediates recruitment to
early endosomes, while interaction with SLC9A3R1 and EZR might
target the protein to specialized subcellular regions, such as
microvilli. {ECO:0000250}.
-!- ALTERNATIVE PRODUCTS:
Event=Alternative splicing; Named isoforms=3;
Comment=Additional isoforms seem to exist.;
Name=5-HT4L;
IsoId=Q62758-1; Sequence=Displayed;
Name=5-HT4S;
IsoId=Q62758-2; Sequence=VSP_001854;
Name=5-HT4(E);
IsoId=Q62758-3; Sequence=VSP_001855;
-!- TISSUE SPECIFICITY: In brain, isoform 5-HT4S is restricted to the
striatum, but isoform 5-HT4L is expressed throughout the brain,
except in the cerebellum. In peripheral tissues, differential
expression is also observed in the atrium of the heart where only
isoform 5-HT4S is detectable.
-!- SIMILARITY: Belongs to the G-protein coupled receptor 1 family.
{ECO:0000255|PROSITE-ProRule:PRU00521}.
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EMBL; U20907; AAC52233.1; -; mRNA.
EMBL; U20906; AAC52232.1; -; mRNA.
EMBL; Z48153; CAA88170.1; -; mRNA.
EMBL; AJ011370; CAA09599.1; -; mRNA.
PIR; S55549; S55549.
PIR; S55550; S55550.
RefSeq; NP_036985.1; NM_012853.1. [Q62758-1]
UniGene; Rn.10094; -.
ProteinModelPortal; Q62758; -.
STRING; 10116.ENSRNOP00000025892; -.
BindingDB; Q62758; -.
ChEMBL; CHEMBL4317; -.
GuidetoPHARMACOLOGY; 9; -.
PhosphoSitePlus; Q62758; -.
PaxDb; Q62758; -.
PRIDE; Q62758; -.
GeneID; 25324; -.
KEGG; rno:25324; -.
UCSC; RGD:2850; rat. [Q62758-1]
CTD; 3360; -.
RGD; 2850; Htr4.
eggNOG; KOG3656; Eukaryota.
eggNOG; ENOG410XRW9; LUCA.
HOGENOM; HOG000239242; -.
HOVERGEN; HBG106962; -.
InParanoid; Q62758; -.
KO; K04160; -.
PhylomeDB; Q62758; -.
PRO; PR:Q62758; -.
Proteomes; UP000002494; Unplaced.
GO; GO:0005768; C:endosome; IEA:UniProtKB-SubCell.
GO; GO:0005887; C:integral component of plasma membrane; IEA:InterPro.
GO; GO:0004993; F:G-protein coupled serotonin receptor activity; IMP:RGD.
GO; GO:0007189; P:adenylate cyclase-activating G-protein coupled receptor signaling pathway; IMP:RGD.
GO; GO:0007268; P:chemical synaptic transmission; IEA:InterPro.
GO; GO:0050890; P:cognition; TAS:RGD.
GO; GO:0007214; P:gamma-aminobutyric acid signaling pathway; IMP:RGD.
GO; GO:0032098; P:regulation of appetite; IEA:InterPro.
CDD; cd15056; 7tmA_5-HT4; 1.
InterPro; IPR001520; 5HT4_rcpt.
InterPro; IPR000276; GPCR_Rhodpsn.
InterPro; IPR017452; GPCR_Rhodpsn_7TM.
Pfam; PF00001; 7tm_1; 1.
PRINTS; PR01059; 5HT4RECEPTR.
PRINTS; PR00237; GPCRRHODOPSN.
SMART; SM01381; 7TM_GPCR_Srsx; 1.
PROSITE; PS00237; G_PROTEIN_RECEP_F1_1; 1.
PROSITE; PS50262; G_PROTEIN_RECEP_F1_2; 1.
2: Evidence at transcript level;
Alternative splicing; Cell membrane; Complete proteome;
Disulfide bond; Endosome; G-protein coupled receptor; Glycoprotein;
Lipoprotein; Membrane; Palmitate; Receptor; Reference proteome;
Transducer; Transmembrane; Transmembrane helix.
CHAIN 1 406 5-hydroxytryptamine receptor 4.
/FTId=PRO_0000068968.
TOPO_DOM 1 19 Extracellular. {ECO:0000250}.
TRANSMEM 20 40 Helical; Name=1. {ECO:0000250}.
TOPO_DOM 41 58 Cytoplasmic. {ECO:0000250}.
TRANSMEM 59 79 Helical; Name=2. {ECO:0000250}.
TOPO_DOM 80 93 Extracellular. {ECO:0000250}.
TRANSMEM 94 116 Helical; Name=3. {ECO:0000250}.
TOPO_DOM 117 137 Cytoplasmic. {ECO:0000250}.
TRANSMEM 138 158 Helical; Name=4. {ECO:0000250}.
TOPO_DOM 159 192 Extracellular. {ECO:0000250}.
TRANSMEM 193 213 Helical; Name=5. {ECO:0000250}.
TOPO_DOM 214 260 Cytoplasmic. {ECO:0000250}.
TRANSMEM 261 281 Helical; Name=6. {ECO:0000250}.
TOPO_DOM 282 294 Extracellular. {ECO:0000250}.
TRANSMEM 295 315 Helical; Name=7. {ECO:0000250}.
TOPO_DOM 316 406 Cytoplasmic. {ECO:0000250}.
LIPID 329 329 S-palmitoyl cysteine. {ECO:0000250}.
CARBOHYD 7 7 N-linked (GlcNAc...) asparagine.
{ECO:0000255}.
DISULFID 93 184 {ECO:0000255|PROSITE-ProRule:PRU00521}.
VAR_SEQ 359 406 RDTVECGGQWESRCHLTATSPLVAAQPVIRRPQDNDLEDSC
SLKRSQS -> SFPLLFCNRPVPV (in isoform 5-
HT4(E)). {ECO:0000305}.
/FTId=VSP_001855.
VAR_SEQ 360 406 DTVECGGQWESRCHLTATSPLVAAQPVIRRPQDNDLEDSCS
LKRSQS -> YTVLHSGQHQELEKLPIHNDPESLESCF
(in isoform 5-HT4S). {ECO:0000305}.
/FTId=VSP_001854.
CONFLICT 74 75 NA -> MP (in Ref. 3; CAA09599).
{ECO:0000305}.
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


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