5HT4R_MOUSE
ID 5HT4R_MOUSE Reviewed; 388 AA.
AC P97288; O89003; O89004; Q3URB5; Q9R2A4;
DT 15-JUL-1998, integrated into UniProtKB/Swiss-Prot.
DT 27-JUL-2011, sequence version 3.
DT 03-AUG-2022, entry version 184.
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 Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=SWR/J; TISSUE=Brain;
RX PubMed=8946946; DOI=10.1016/s0014-5793(96)01132-5;
RA Claeysen S., Sebben M., Journot L., Bockaert J., Dumuis A.;
RT "Cloning, expression and pharmacology of the mouse 5-HT(4L) receptor.";
RL FEBS Lett. 398:19-25(1996).
RN [2]
RP SEQUENCE REVISION TO C-TERMINUS.
RA Dumuis A.;
RL Submitted (SEP-1998) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 5-HT4(A) AND 5-HT4(E)).
RC STRAIN=SWR/J; TISSUE=Brain;
RX PubMed=9928238; DOI=10.1111/j.1749-6632.1998.tb10172.x;
RA Claeysen S., Faye P., Sebben M., Taviaux S., Bockaert J., Dumuis A.;
RT "5-HT4 receptors: cloning and expression of new splice variants.";
RL Ann. N. Y. Acad. Sci. 861:49-56(1998).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 5-HT4(F)).
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 [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP INTERACTION WITH PATJ; MAGI2; MPP3; NOS1; SEC23A; SLC9A3R1 AND SNX27.
RX PubMed=15466885; DOI=10.1242/jcs.01379;
RA Joubert L., Hanson B., Barthet G., Sebben M., Claeysen S., Hong W.,
RA Marin P., Dumuis A., Bockaert J.;
RT "New sorting nexin (SNX27) and NHERF specifically interact with the 5-HT4a
RT receptor splice variant: roles in receptor targeting.";
RL J. Cell Sci. 117:5367-5379(2004).
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 (By
CC similarity). {ECO:0000250}.
CC -!- SUBUNIT: Isoform 5-HT4(A) interacts with MAGI2, MPP3, SLC9A3R1 and
CC SNX27 isoforms 1 and 2. Isoform 5-HT4(E) interacts with PATJ, NOS1 and
CC SEC23A. Isoform 5-HT4(A) forms a complex including SLC9A3R1 and EZR.
CC Interacts (via C-terminus 330-346 AA) with GRK5; this interaction is
CC promoted by 5-HT (serotonin) (By similarity). {ECO:0000250}.
CC -!- INTERACTION:
CC P97288; P34947: GRK5; Xeno; NbExp=8; IntAct=EBI-7149283, EBI-7149314;
CC P97288; P12931: SRC; Xeno; NbExp=2; IntAct=EBI-7149283, EBI-621482;
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 -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=4;
CC Name=1;
CC IsoId=P97288-1; Sequence=Displayed;
CC Name=5-HT4(A);
CC IsoId=P97288-2; Sequence=VSP_001851;
CC Name=5-HT4(E);
CC IsoId=P97288-3; Sequence=VSP_001852;
CC Name=5-HT4(F);
CC IsoId=P97288-4; Sequence=VSP_001853;
CC -!- SIMILARITY: Belongs to the G-protein coupled receptor 1 family.
CC {ECO:0000255|PROSITE-ProRule:PRU00521}.
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DR EMBL; Y09585; CAA70773.1; -; mRNA.
DR EMBL; Y09587; CAA70775.1; -; mRNA.
DR EMBL; Y09588; CAA70776.1; -; mRNA.
DR EMBL; AJ011369; CAA09598.1; -; mRNA.
DR EMBL; AK141587; BAE24750.1; -; mRNA.
DR EMBL; AK141625; BAE24773.1; -; mRNA.
DR EMBL; CH466528; EDL09743.1; -; Genomic_DNA.
DR CCDS; CCDS29291.1; -. [P97288-1]
DR CCDS; CCDS89256.1; -. [P97288-4]
DR CCDS; CCDS89257.1; -. [P97288-2]
DR RefSeq; NP_032339.2; NM_008313.4. [P97288-1]
DR RefSeq; XP_006525739.1; XM_006525676.3. [P97288-1]
DR RefSeq; XP_006525741.1; XM_006525678.3. [P97288-1]
DR RefSeq; XP_006525743.1; XM_006525680.3. [P97288-2]
DR RefSeq; XP_006525746.1; XM_006525683.3. [P97288-3]
DR RefSeq; XP_017173328.1; XM_017317839.1.
DR AlphaFoldDB; P97288; -.
DR SMR; P97288; -.
DR IntAct; P97288; 5.
DR MINT; P97288; -.
DR STRING; 10090.ENSMUSP00000027560; -.
DR BindingDB; P97288; -.
DR ChEMBL; CHEMBL2183; -.
DR DrugCentral; P97288; -.
DR GuidetoPHARMACOLOGY; 9; -.
DR GlyGen; P97288; 1 site.
DR PhosphoSitePlus; P97288; -.
DR SwissPalm; P97288; -.
DR PaxDb; P97288; -.
DR PRIDE; P97288; -.
DR ProteomicsDB; 285994; -. [P97288-1]
DR ProteomicsDB; 285995; -. [P97288-2]
DR ProteomicsDB; 285996; -. [P97288-3]
DR ProteomicsDB; 285997; -. [P97288-4]
DR Antibodypedia; 15936; 453 antibodies from 33 providers.
DR DNASU; 15562; -.
DR Ensembl; ENSMUST00000027560; ENSMUSP00000027560; ENSMUSG00000026322. [P97288-1]
DR Ensembl; ENSMUST00000236691; ENSMUSP00000157470; ENSMUSG00000026322. [P97288-4]
DR Ensembl; ENSMUST00000238081; ENSMUSP00000157967; ENSMUSG00000026322. [P97288-2]
DR GeneID; 15562; -.
DR KEGG; mmu:15562; -.
DR UCSC; uc008fda.1; mouse. [P97288-1]
DR UCSC; uc008fdb.1; mouse. [P97288-2]
DR UCSC; uc008fdc.1; mouse. [P97288-4]
DR CTD; 3360; -.
DR MGI; MGI:109246; Htr4.
DR VEuPathDB; HostDB:ENSMUSG00000026322; -.
DR eggNOG; KOG3656; Eukaryota.
DR GeneTree; ENSGT00940000155983; -.
DR HOGENOM; CLU_009579_11_0_1; -.
DR InParanoid; P97288; -.
DR OMA; AHQIRIL; -.
DR OrthoDB; 750855at2759; -.
DR PhylomeDB; P97288; -.
DR TreeFam; TF316350; -.
DR Reactome; R-MMU-390666; Serotonin receptors.
DR Reactome; R-MMU-418555; G alpha (s) signalling events.
DR BioGRID-ORCS; 15562; 2 hits in 73 CRISPR screens.
DR ChiTaRS; Htr4; mouse.
DR PRO; PR:P97288; -.
DR Proteomes; UP000000589; Chromosome 18.
DR RNAct; P97288; protein.
DR Bgee; ENSMUSG00000026322; Expressed in lumbar dorsal root ganglion and 68 other tissues.
DR ExpressionAtlas; P97288; baseline and differential.
DR Genevisible; P97288; MM.
DR GO; GO:0005737; C:cytoplasm; ISO:MGI.
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:MGI.
DR GO; GO:0045202; C:synapse; IEA:GOC.
DR GO; GO:0004993; F:G protein-coupled serotonin receptor activity; ISO:MGI.
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; ISO:MGI.
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: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; ISO:MGI.
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 1: Evidence at protein 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..388
FT /note="5-hydroxytryptamine receptor 4"
FT /id="PRO_0000068966"
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 359..388
FT /note="RDTVECGGQWESRCHLTATSPLVAAQPSDT -> SFPLLFRNRPVPV (in
FT isoform 5-HT4(E))"
FT /evidence="ECO:0000305"
FT /id="VSP_001852"
FT VAR_SEQ 360..388
FT /note="DTVECGGQWESRCHLTATSPLVAAQPSDT -> YTVLHSGHHQELEKLPIHN
FT DPESLESCF (in isoform 5-HT4(A))"
FT /evidence="ECO:0000305"
FT /id="VSP_001851"
FT VAR_SEQ 360..388
FT /note="DTVECGGQWESRCHLTATSPLVAAQPSDT -> PVPV (in isoform 5-
FT HT4(F))"
FT /evidence="ECO:0000305"
FT /id="VSP_001853"
FT CONFLICT 361
FT /note="T -> A (in Ref. 1; CAA70773)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 388 AA; 43962 MW; F84163E7CAE415B0 CRC64;
MDKLDANVSS NEGFRSVEKV VLLTFLAVVI LMAILGNLLV MVAVCRDRQL RKIKTNYFIV
SLAFADLLVS VLVMPFGAIE LVQDIWAYGE MFCLVRTSLD VLLTTASIFH LCCISLDRYY
AICCQPLVYR NKMTPLRIAL MLGGCWVLPM FISFLPIMQG WNNIGIVDVI EKRKFSHNSN
STWCVFMVNK PYAITCSVVA FYIPFLLMVL AYYRIYVTAK EHAQQIQMLQ RAGATSESRP
QPADQHSTHR MRTETKAAKT LCVIMGCFCF CWAPFFVTNI VDPFIDYTVP EQVWTAFLWL
GYINSGLNPF LYAFLNKSFR RAFLIILCCD DERYKRPPIL GQTVPCSTTT INGSTHVLRD
TVECGGQWES RCHLTATSPL VAAQPSDT
