5HT4R_RAT
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 25-MAY-2022, entry version 153.
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, SLC9A3R1, SEC23A
CC and SNX27. May form a complex including SLC9A3R1 and EZR (By
CC similarity). Interacts (via C-terminus 330-346 AA) with GRK5; this
CC interaction is promoted by 5-HT (serotonin) (By similarity).
CC {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 SLC9A3R1 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}.
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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. [Q62758-1]
DR AlphaFoldDB; Q62758; -.
DR SMR; Q62758; -.
DR STRING; 10116.ENSRNOP00000025892; -.
DR BindingDB; Q62758; -.
DR ChEMBL; CHEMBL4317; -.
DR DrugCentral; Q62758; -.
DR GuidetoPHARMACOLOGY; 9; -.
DR GlyGen; Q62758; 1 site.
DR PhosphoSitePlus; Q62758; -.
DR PaxDb; Q62758; -.
DR GeneID; 25324; -.
DR KEGG; rno:25324; -.
DR UCSC; RGD:2850; rat. [Q62758-1]
DR CTD; 3360; -.
DR RGD; 2850; Htr4.
DR eggNOG; KOG3656; Eukaryota.
DR InParanoid; Q62758; -.
DR OrthoDB; 750855at2759; -.
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:0005887; C:integral component of plasma membrane; IBA:GO_Central.
DR GO; GO:0016020; C: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:0051378; F:serotonin binding; IBA:GO_Central.
DR GO; GO:0007189; P:adenylate cyclase-activating G protein-coupled receptor signaling pathway; IMP:RGD.
DR GO; GO:0007198; P:adenylate cyclase-inhibiting serotonin receptor signaling pathway; IBA:GO_Central.
DR GO; GO:0007268; P:chemical synaptic transmission; IBA:GO_Central.
DR GO; GO:0050890; P:cognition; TAS: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:0032098; P:regulation of appetite; IEA:InterPro.
DR InterPro; IPR001520; 5HT4_rcpt.
DR InterPro; IPR000276; GPCR_Rhodpsn.
DR InterPro; IPR017452; GPCR_Rhodpsn_7TM.
DR Pfam; PF00001; 7tm_1; 1.
DR PRINTS; PR01059; 5HT4RECEPTR.
DR PRINTS; PR00237; GPCRRHODOPSN.
DR SMART; SM01381; 7TM_GPCR_Srsx; 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
