P97288 (5HT4R_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
5-hydroxytryptamine receptor 4
Short name=5-HT-4
Short name=5-HT4

Alternative name(s):
Serotonin receptor 4

Gene names

Name:

Htr4

Organism

Mus musculus (Mouse) [Reference proteome]

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › Mus

Protein attributes

Sequence length	388 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

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 By similarity.
Subunit structure	Isoform 5-HT4(A) interacts with MAGI2, MPP3, SLC9A3R1 and SNX27 isoforms 1 and 2. Isoform 5-HT4(E) interacts with INADL, NOS1 and SEC23A. Isoform 5-HT4(A) forms a complex including SLC9A3R1 and EZR. Interacts (via C-terminus 330-346 AA) with GRK5; this interaction is promoted by 5-HT (serotonin) By similarity. Ref.7
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.
Sequence similarities	Belongs to the G-protein coupled receptor 1 family.

Ontologies

Keywords
Cellular component	Cell membrane Endosome Membrane
Coding sequence diversity	Alternative splicing
Domain	Transmembrane Transmembrane helix
Molecular function	G-protein coupled receptor Receptor Transducer
PTM	Disulfide bond Glycoprotein Lipoprotein Palmitate
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	positive regulation of cell proliferation Inferred from electronic annotation. Source: Compara
Cellular_component	endosome Inferred from electronic annotation. Source: UniProtKB-SubCell integral to membrane Inferred from electronic annotation. Source: UniProtKB-KW plasma membrane Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular_function	serotonin receptor activity Inferred from electronic annotation. Source: Compara
Complete GO annotation...

Alternative products

This entry describes 4 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: P97288-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

Isoform 5-HT4(A) (identifier: P97288-2)

The sequence of this isoform differs from the canonical sequence as follows:
     360-388: DTVECGGQWESRCHLTATSPLVAAQPSDT → YTVLHSGHHQELEKLPIHNDPESLESCF

Isoform 5-HT4(E) (identifier: P97288-3)

The sequence of this isoform differs from the canonical sequence as follows:
     359-388: RDTVECGGQWESRCHLTATSPLVAAQPSDT → SFPLLFRNRPVPV

Isoform 5-HT4(F) (identifier: P97288-4)

The sequence of this isoform differs from the canonical sequence as follows:
     360-388: DTVECGGQWESRCHLTATSPLVAAQPSDT → PVPV

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 388	388	5-hydroxytryptamine receptor 4		PRO_0000068966
Regions
	Topological domain	1 – 19	19	Extracellular By similarity
	Transmembrane	20 – 40	21	Helical; Name=1; By similarity
	Topological domain	41 – 58	18	Cytoplasmic By similarity
	Transmembrane	59 – 79	21	Helical; Name=2; By similarity
	Topological domain	80 – 93	14	Extracellular By similarity
	Transmembrane	94 – 116	23	Helical; Name=3; By similarity
	Topological domain	117 – 137	21	Cytoplasmic By similarity
	Transmembrane	138 – 158	21	Helical; Name=4; By similarity
	Topological domain	159 – 192	34	Extracellular By similarity
	Transmembrane	193 – 213	21	Helical; Name=5; By similarity
	Topological domain	214 – 260	47	Cytoplasmic By similarity
	Transmembrane	261 – 281	21	Helical; Name=6; By similarity
	Topological domain	282 – 294	13	Extracellular By similarity
	Transmembrane	295 – 315	21	Helical; Name=7; By similarity
	Topological domain	316 – 388	73	Cytoplasmic By similarity
Amino acid modifications
	Lipidation	329	1	S-palmitoyl cysteine By similarity
	Glycosylation	7	1	N-linked (GlcNAc...) Potential
	Disulfide bond	93 ↔ 184		By similarity
Natural variations
	Alternative sequence	359 – 388	30	RDTVE…QPSDT → SFPLLFRNRPVPV in isoform 5-HT4(E).		VSP_001852
	Alternative sequence	360 – 388	29	DTVEC…QPSDT → YTVLHSGHHQELEKLPIHND PESLESCF in isoform 5-HT4(A).		VSP_001851
	Alternative sequence	360 – 388	29	DTVEC…QPSDT → PVPV in isoform 5-HT4(F).		VSP_001853
Experimental info
	Sequence conflict	361	1	T → A in CAA70773. Ref.1

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified July 27, 2011. Version 3. Checksum: F84163E7CAE415B0	FASTA	388	43,962
	10 20 30 40 50 60 MDKLDANVSS NEGFRSVEKV VLLTFLAVVI LMAILGNLLV MVAVCRDRQL RKIKTNYFIV 70 80 90 100 110 120 SLAFADLLVS VLVMPFGAIE LVQDIWAYGE MFCLVRTSLD VLLTTASIFH LCCISLDRYY 130 140 150 160 170 180 AICCQPLVYR NKMTPLRIAL MLGGCWVLPM FISFLPIMQG WNNIGIVDVI EKRKFSHNSN 190 200 210 220 230 240 STWCVFMVNK PYAITCSVVA FYIPFLLMVL AYYRIYVTAK EHAQQIQMLQ RAGATSESRP 250 260 270 280 290 300 QPADQHSTHR MRTETKAAKT LCVIMGCFCF CWAPFFVTNI VDPFIDYTVP EQVWTAFLWL 310 320 330 340 350 360 GYINSGLNPF LYAFLNKSFR RAFLIILCCD DERYKRPPIL GQTVPCSTTT INGSTHVLRD 370 380 TVECGGQWES RCHLTATSPL VAAQPSDT
	Isoform 5-HT4(A) [UniParc]. Checksum: 2EE398916C432032	FASTA	387	44,162
	10 20 30 40 50 60 MDKLDANVSS NEGFRSVEKV VLLTFLAVVI LMAILGNLLV MVAVCRDRQL RKIKTNYFIV 70 80 90 100 110 120 SLAFADLLVS VLVMPFGAIE LVQDIWAYGE MFCLVRTSLD VLLTTASIFH LCCISLDRYY 130 140 150 160 170 180 AICCQPLVYR NKMTPLRIAL MLGGCWVLPM FISFLPIMQG WNNIGIVDVI EKRKFSHNSN 190 200 210 220 230 240 STWCVFMVNK PYAITCSVVA FYIPFLLMVL AYYRIYVTAK EHAQQIQMLQ RAGATSESRP 250 260 270 280 290 300 QPADQHSTHR MRTETKAAKT LCVIMGCFCF CWAPFFVTNI VDPFIDYTVP EQVWTAFLWL 310 320 330 340 350 360 GYINSGLNPF LYAFLNKSFR RAFLIILCCD DERYKRPPIL GQTVPCSTTT INGSTHVLRY 370 380 TVLHSGHHQE LEKLPIHNDP ESLESCF
	Isoform 5-HT4(E) [UniParc]. Checksum: D1AD0ACD3D1C8129	FASTA	371	42,287
	10 20 30 40 50 60 MDKLDANVSS NEGFRSVEKV VLLTFLAVVI LMAILGNLLV MVAVCRDRQL RKIKTNYFIV 70 80 90 100 110 120 SLAFADLLVS VLVMPFGAIE LVQDIWAYGE MFCLVRTSLD VLLTTASIFH LCCISLDRYY 130 140 150 160 170 180 AICCQPLVYR NKMTPLRIAL MLGGCWVLPM FISFLPIMQG WNNIGIVDVI EKRKFSHNSN 190 200 210 220 230 240 STWCVFMVNK PYAITCSVVA FYIPFLLMVL AYYRIYVTAK EHAQQIQMLQ RAGATSESRP 250 260 270 280 290 300 QPADQHSTHR MRTETKAAKT LCVIMGCFCF CWAPFFVTNI VDPFIDYTVP EQVWTAFLWL 310 320 330 340 350 360 GYINSGLNPF LYAFLNKSFR RAFLIILCCD DERYKRPPIL GQTVPCSTTT INGSTHVLSF 370 PLLFRNRPVP V
	Isoform 5-HT4(F) [UniParc]. Checksum: 2C8C6F05B22CF91C	FASTA	363	41,312
	10 20 30 40 50 60 MDKLDANVSS NEGFRSVEKV VLLTFLAVVI LMAILGNLLV MVAVCRDRQL RKIKTNYFIV 70 80 90 100 110 120 SLAFADLLVS VLVMPFGAIE LVQDIWAYGE MFCLVRTSLD VLLTTASIFH LCCISLDRYY 130 140 150 160 170 180 AICCQPLVYR NKMTPLRIAL MLGGCWVLPM FISFLPIMQG WNNIGIVDVI EKRKFSHNSN 190 200 210 220 230 240 STWCVFMVNK PYAITCSVVA FYIPFLLMVL AYYRIYVTAK EHAQQIQMLQ RAGATSESRP 250 260 270 280 290 300 QPADQHSTHR MRTETKAAKT LCVIMGCFCF CWAPFFVTNI VDPFIDYTVP EQVWTAFLWL 310 320 330 340 350 360 GYINSGLNPF LYAFLNKSFR RAFLIILCCD DERYKRPPIL GQTVPCSTTT INGSTHVLRP VPV

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Cloning, expression and pharmacology of the mouse 5-HT(4L) receptor." Claeysen S., Sebben M., Journot L., Bockaert J., Dumuis A. FEBS Lett. 398:19-25(1996) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Strain: Swiss. Tissue: Brain.
[2]	Dumuis A. Submitted (SEP-1998) to the EMBL/GenBank/DDBJ databases Cited for: SEQUENCE REVISION TO C-TERMINUS.
[3]	"5-HT4 receptors: cloning and expression of new splice variants." Claeysen S., Faye P., Sebben M., Taviaux S., Bockaert J., Dumuis A. Ann. N. Y. Acad. Sci. 861:49-56(1998) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 5-HT4(A) AND 5-HT4(E)). Strain: Swiss. Tissue: Brain.
[4]	"Novel brain-specific 5-HT4 receptor splice variants show marked constitutive activity: role of the C-terminal intracellular domain." Claeysen S., Sebben M., Becamel C., Bockaert J., Dumuis A. Mol. Pharmacol. 55:910-920(1999) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 5-HT4(F)). Tissue: Brain.
[5]	"The transcriptional landscape of the mammalian genome." Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J. , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y. Science 309:1559-1563(2005) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[6]	Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C. Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[7]	"New sorting nexin (SNX27) and NHERF specifically interact with the 5-HT4a receptor splice variant: roles in receptor targeting." Joubert L., Hanson B., Barthet G., Sebben M., Claeysen S., Hong W., Marin P., Dumuis A., Bockaert J. J. Cell Sci. 117:5367-5379(2004) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH INADL; MAGI2; MPP3; NOS1; SEC23A; SLC9A3R1 AND SNX27.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	Y09585 mRNA. Translation: CAA70773.1. Y09587 mRNA. Translation: CAA70775.1. Y09588 mRNA. Translation: CAA70776.1. AJ011369 mRNA. Translation: CAA09598.1. AK141587 mRNA. Translation: BAE24750.1. AK141625 mRNA. Translation: BAE24773.1. CH466528 Genomic DNA. Translation: EDL09743.1.
IPI	IPI00122961. IPI00223494. IPI00223495. IPI00223496.
RefSeq	NP_032339.2. NM_008313.4.
UniGene	Mm.20440.
3D structure databases
ProteinModelPortal	P97288.
SMR	P97288. Positions 25-328.
ModBase	Search...
Protein family/group databases
GPCRDB	Search...
PTM databases
PhosphoSite	P97288.
Proteomic databases
PRIDE	P97288.
Protocols and materials databases
DNASU	15562.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENSMUST00000027560; ENSMUSP00000027560; ENSMUSG00000026322.
GeneID	15562.
KEGG	mmu:15562.
UCSC	uc008fdb.1. mouse. uc008fdc.1. mouse.
Organism-specific databases
CTD	3360.
MGI	MGI:109246. Htr4.
Phylogenomic databases
eggNOG	NOG262978.
GeneTree	ENSGT00700000104179.
HOGENOM	HOG000239242.
HOVERGEN	HBG106962.
InParanoid	Q3URB5.
KO	K04160.
OMA	YRIYITA.
OrthoDB	EOG4933HZ.
Gene expression databases
Bgee	P97288.
CleanEx	MM_HTR4.
Genevestigator	P97288.
GermOnline	ENSMUSG00000026322. Mus musculus.
Family and domain databases
InterPro	IPR001520. 5HT4_rcpt. IPR000276. GPCR_Rhodpsn. IPR017452. GPCR_Rhodpsn_7TM. [Graphical view]
Pfam	PF00001. 7tm_1. 1 hit. [Graphical view]
PRINTS	PR01059. 5HT4RECEPTR. PR00237. GPCRRHODOPSN.
PROSITE	PS00237. G_PROTEIN_RECEP_F1_1. 1 hit. PS50262. G_PROTEIN_RECEP_F1_2. 1 hit. [Graphical view]
ProtoNet	Search...
Other
BindingDB	P97288.
ChEMBL	CHEMBL2183.
NextBio	288518.
SOURCE	Search...

Entry information

Entry name

5HT4R_MOUSE

Accession

Primary (citable) accession number: P97288
Secondary accession number(s): O89003 , O89004, Q3URB5, Q9R2A4

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 15, 1998
Last sequence update:	July 27, 2011
Last modified:	May 1, 2013
This is version 112 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program