5-hydroxytryptamine receptor 4 - Homo sapiens (Human)

Preferred order of sections

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

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

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.
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 By similarity. Interacts (via C-terminus 330-346 AA) with GRK5; this interaction is promoted by 5-HT (serotonin). Ref.9
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 By similarity.
Tissue specificity	Isoform 5-HT4(A) is expressed in ileum, brain, and atrium, but not in the ventricle.
Sequence similarities	Belongs to the G-protein coupled receptor 1 family.

Ontologies

Keywords
Cellular component	Cell membrane Endosome Membrane
Coding sequence diversity	Alternative splicing Polymorphism
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	G-protein signaling, coupled to cyclic nucleotide second messenger Traceable author statement. Source: ProtInc positive regulation of cell proliferation Inferred from mutant phenotype. Source: UniProtKB
Cellular component	endosome Inferred from electronic annotation. Source: UniProtKB-SubCell integral to plasma membrane Traceable author statement. Source: ProtInc membrane fraction Inferred from direct assay. Source: MGI
Molecular function	serotonin receptor activity Inferred from direct assay. Source: MGI
Complete GO annotation...

Alternative products

This entry describes 7 isoforms produced by alternative splicing. [Align] [Select]

Note: Additional isoforms seem to exist.

Isoform 5-HT4(B) (identifier: Q13639-1)

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: Q13639-2)

Also known as: 5-HT4S;

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

Isoform 5-HT4(C) (identifier: Q13639-3)

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

Isoform 5-HT4(D) (identifier: Q13639-4)

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

Isoform 5-HT4(E) (identifier: Q13639-5)

Also known as: H5-HT4(g);

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

Isoform 5-HT4(F) (identifier: Q13639-6)

The sequence of this isoform differs from the canonical sequence as follows:
169-169: L → LERSLNQGLGQDFHA

Isoform 5-HT4(G) (identifier: Q13639-7)

The sequence of this isoform differs from the canonical sequence as follows:
360-388: Missing.

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 388

388

5-hydroxytryptamine receptor 4

PRO_0000068965

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

169

1

L → LERSLNQGLGQDFHA in isoform 5-HT4(F).

VSP_001845

Alternative sequence

359 – 388

30

RDAVE…QPSDT → SSGTETDRRNFGIRKRRLTK PS in isoform 5-HT4(D).

VSP_001847

Alternative sequence

359 – 388

30

RDAVE…QPSDT → SGCSPVSSFLLLFCNRPVPV in isoform 5-HT4(E).

VSP_001846

Alternative sequence

360 – 388

29

DAVEC…QPSDT → YTVLHRGHHQELEKLPIHND PESLESCF in isoform 5-HT4(A).

VSP_001849

Alternative sequence

360 – 388

29

DAVEC…QPSDT → F in isoform 5-HT4(C).

VSP_001848

Alternative sequence

360 – 388

29

Missing in isoform 5-HT4(G).

VSP_001850

Natural variant

372

1

C → Y. [dbSNP:rs34826744]

VAR_049364

Sequences

Sequence		Length	Mass (Da)
Isoform 5-HT4(B) [UniParc]. Last modified January 11, 2001. Version 2. Checksum: 7FCFEC60E7BDF560 Show »	FASTA	388	43,761
10 20 30 40 50 60 MDKLDANVSS EEGFGSVEKV VLLTFLSTVI LMAILGNLLV MVAVCWDRQL RKIKTNYFIV 70 80 90 100 110 120 SLAFADLLVS VLVMPFGAIE LVQDIWIYGE VFCLVRTSLD VLLTTASIFH LCCISLDRYY 130 140 150 160 170 180 AICCQPLVYR NKMTPLRIAL MLGGCWVIPT FISFLPIMQG WNNIGIIDLI EKRKFNQNSN 190 200 210 220 230 240 STYCVFMVNK PYAITCSVVA FYIPFLLMVL AYYRIYVTAK EHAHQIQMLQ RAGASSESRP 250 260 270 280 290 300 QSADQHSTHR MRTETKAAKT LCIIMGCFCL CWAPFFVTNI VDPFIDYTVP GQVWTAFLWL 310 320 330 340 350 360 GYINSGLNPF LYAFLNKSFR RAFLIILCCD DERYRRPSIL GQTVPCSTTT INGSTHVLRD 370 380 AVECGGQWES QCHPPATSPL VAAQPSDT « Hide
Isoform 5-HT4(A) (5-HT4S) [UniParc]. Checksum: 43019BED75AC9D0F Show »	FASTA	387	44,109
10 20 30 40 50 60 MDKLDANVSS EEGFGSVEKV VLLTFLSTVI LMAILGNLLV MVAVCWDRQL RKIKTNYFIV 70 80 90 100 110 120 SLAFADLLVS VLVMPFGAIE LVQDIWIYGE VFCLVRTSLD VLLTTASIFH LCCISLDRYY 130 140 150 160 170 180 AICCQPLVYR NKMTPLRIAL MLGGCWVIPT FISFLPIMQG WNNIGIIDLI EKRKFNQNSN 190 200 210 220 230 240 STYCVFMVNK PYAITCSVVA FYIPFLLMVL AYYRIYVTAK EHAHQIQMLQ RAGASSESRP 250 260 270 280 290 300 QSADQHSTHR MRTETKAAKT LCIIMGCFCL CWAPFFVTNI VDPFIDYTVP GQVWTAFLWL 310 320 330 340 350 360 GYINSGLNPF LYAFLNKSFR RAFLIILCCD DERYRRPSIL GQTVPCSTTT INGSTHVLRY 370 380 TVLHRGHHQE LEKLPIHNDP ESLESCF « Hide
Isoform 5-HT4(C) [UniParc]. Checksum: F2BE6033F518178A Show »	FASTA	360	40,944
10 20 30 40 50 60 MDKLDANVSS EEGFGSVEKV VLLTFLSTVI LMAILGNLLV MVAVCWDRQL RKIKTNYFIV 70 80 90 100 110 120 SLAFADLLVS VLVMPFGAIE LVQDIWIYGE VFCLVRTSLD VLLTTASIFH LCCISLDRYY 130 140 150 160 170 180 AICCQPLVYR NKMTPLRIAL MLGGCWVIPT FISFLPIMQG WNNIGIIDLI EKRKFNQNSN 190 200 210 220 230 240 STYCVFMVNK PYAITCSVVA FYIPFLLMVL AYYRIYVTAK EHAHQIQMLQ RAGASSESRP 250 260 270 280 290 300 QSADQHSTHR MRTETKAAKT LCIIMGCFCL CWAPFFVTNI VDPFIDYTVP GQVWTAFLWL 310 320 330 340 350 360 GYINSGLNPF LYAFLNKSFR RAFLIILCCD DERYRRPSIL GQTVPCSTTT INGSTHVLRF « Hide
Isoform 5-HT4(D) [UniParc]. Checksum: C7591BFE6A9C1D62 Show »	FASTA	380	43,186
10 20 30 40 50 60 MDKLDANVSS EEGFGSVEKV VLLTFLSTVI LMAILGNLLV MVAVCWDRQL RKIKTNYFIV 70 80 90 100 110 120 SLAFADLLVS VLVMPFGAIE LVQDIWIYGE VFCLVRTSLD VLLTTASIFH LCCISLDRYY 130 140 150 160 170 180 AICCQPLVYR NKMTPLRIAL MLGGCWVIPT FISFLPIMQG WNNIGIIDLI EKRKFNQNSN 190 200 210 220 230 240 STYCVFMVNK PYAITCSVVA FYIPFLLMVL AYYRIYVTAK EHAHQIQMLQ RAGASSESRP 250 260 270 280 290 300 QSADQHSTHR MRTETKAAKT LCIIMGCFCL CWAPFFVTNI VDPFIDYTVP GQVWTAFLWL 310 320 330 340 350 360 GYINSGLNPF LYAFLNKSFR RAFLIILCCD DERYRRPSIL GQTVPCSTTT INGSTHVLSS 370 380 GTETDRRNFG IRKRRLTKPS « Hide
Isoform 5-HT4(E) (H5-HT4(g)) [UniParc]. Checksum: E45038FEF832270D Show »	FASTA	378	42,746
10 20 30 40 50 60 MDKLDANVSS EEGFGSVEKV VLLTFLSTVI LMAILGNLLV MVAVCWDRQL RKIKTNYFIV 70 80 90 100 110 120 SLAFADLLVS VLVMPFGAIE LVQDIWIYGE VFCLVRTSLD VLLTTASIFH LCCISLDRYY 130 140 150 160 170 180 AICCQPLVYR NKMTPLRIAL MLGGCWVIPT FISFLPIMQG WNNIGIIDLI EKRKFNQNSN 190 200 210 220 230 240 STYCVFMVNK PYAITCSVVA FYIPFLLMVL AYYRIYVTAK EHAHQIQMLQ RAGASSESRP 250 260 270 280 290 300 QSADQHSTHR MRTETKAAKT LCIIMGCFCL CWAPFFVTNI VDPFIDYTVP GQVWTAFLWL 310 320 330 340 350 360 GYINSGLNPF LYAFLNKSFR RAFLIILCCD DERYRRPSIL GQTVPCSTTT INGSTHVLSG 370 CSPVSSFLLL FCNRPVPV « Hide
Isoform 5-HT4(F) [UniParc]. Checksum: 243F4AE87A6F77FA Show »	FASTA	402	45,315
10 20 30 40 50 60 MDKLDANVSS EEGFGSVEKV VLLTFLSTVI LMAILGNLLV MVAVCWDRQL RKIKTNYFIV 70 80 90 100 110 120 SLAFADLLVS VLVMPFGAIE LVQDIWIYGE VFCLVRTSLD VLLTTASIFH LCCISLDRYY 130 140 150 160 170 180 AICCQPLVYR NKMTPLRIAL MLGGCWVIPT FISFLPIMQG WNNIGIIDLE RSLNQGLGQD 190 200 210 220 230 240 FHAIEKRKFN QNSNSTYCVF MVNKPYAITC SVVAFYIPFL LMVLAYYRIY VTAKEHAHQI 250 260 270 280 290 300 QMLQRAGASS ESRPQSADQH STHRMRTETK AAKTLCIIMG CFCLCWAPFF VTNIVDPFID 310 320 330 340 350 360 YTVPGQVWTA FLWLGYINSG LNPFLYAFLN KSFRRAFLII LCCDDERYRR PSILGQTVPC 370 380 390 400 STTTINGSTH VLRDAVECGG QWESQCHPPA TSPLVAAQPS DT « Hide
Isoform 5-HT4(G) [UniParc]. Checksum: CE6033F518178AF3 Show »	FASTA	359	40,797
10 20 30 40 50 60 MDKLDANVSS EEGFGSVEKV VLLTFLSTVI LMAILGNLLV MVAVCWDRQL RKIKTNYFIV 70 80 90 100 110 120 SLAFADLLVS VLVMPFGAIE LVQDIWIYGE VFCLVRTSLD VLLTTASIFH LCCISLDRYY 130 140 150 160 170 180 AICCQPLVYR NKMTPLRIAL MLGGCWVIPT FISFLPIMQG WNNIGIIDLI EKRKFNQNSN 190 200 210 220 230 240 STYCVFMVNK PYAITCSVVA FYIPFLLMVL AYYRIYVTAK EHAHQIQMLQ RAGASSESRP 250 260 270 280 290 300 QSADQHSTHR MRTETKAAKT LCIIMGCFCL CWAPFFVTNI VDPFIDYTVP GQVWTAFLWL 310 320 330 340 350 GYINSGLNPF LYAFLNKSFR RAFLIILCCD DERYRRPSIL GQTVPCSTTT INGSTHVLR « Hide

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Cloning, expression, and pharmacology of four human 5-hydroxytryptamine 4 receptor isoforms produced by alternative splicing in the carboxyl terminus." Blondel O., Gastineau M., Dahmoune Y., Langlois M., Fischmeister R. J. Neurochem. 70:2252-2261(1998) [PubMed: 9603189] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 5-HT4(A); 5-HT4(B); 5-HT4(C) AND 5-HT4(D)). Tissue: Intestine.
[2]	"Cloning and expression of 5-HT4 receptor species and splice variants." Van den Wyngaert I., Gommeren W., Jurzak M., Verhasselt P., Gordon R., Leysen J., Luyten W., Bender E. Submitted (JUN-1997) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 5-HT4(A) AND 5-HT4(B)). Tissue: Brain.
[3]	"Cloning and expression of human 5-HT4S receptors. Effect of receptor density on their coupling to adenylyl cyclase." Claeysen S., Faye P., Sebben M., Lemaire S., Bockaert J., Dumuis A. NeuroReport 8:3189-3195(1997) [PubMed: 9351641] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 5-HT4(A)). Tissue: Heart.
[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: 10220570] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 5-HT4(E)). Tissue: Brain.
[5]	"Cloning and characterization of multiple human 5-HT4 receptor variants including a novel variant that lacks the alternatively spliced C-terminal exon." Vilaro M.T., Domenech T., Palacios J.M., Mengod G. Submitted (SEP-2000) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 5-HT4(A); 5-HT4(E) AND 5-HT4(G)). Tissue: Hippocampus.
[6]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 5-HT4(B)).
[7]	"Structure of the human serotonin 5-HT4 receptor gene and cloning of a novel 5-HT4 splice variant." Bender E., Pindon A., van Oers I., Zhang Y.B., Gommeren W., Verhasselt P., Jurzak M., Leysen J., Luyten W. J. Neurochem. 74:478-489(2000) [PubMed: 10646498] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 10-388 (ISOFORM 5-HT4(F)).
[8]	"Expression of serotonin receptor mRNAs in blood vessels." Ullmer C., Schmuck K., Kalkman H.O., Luebbert H. FEBS Lett. 370:215-221(1995) [PubMed: 7656980] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 112-255. Tissue: Brain.
[9]	"Beta-arrestin1 phosphorylation by GRK5 regulates G protein-independent 5-HT4 receptor signalling." Barthet G., Carrat G., Cassier E., Barker B., Gaven F., Pillot M., Framery B., Pellissier L.P., Augier J., Kang D.S., Claeysen S., Reiter E., Baneres J.L., Benovic J.L., Marin P., Bockaert J., Dumuis A. EMBO J. 28:2706-2718(2009) [PubMed: 19661922] [Abstract] Cited for: MASS SPECTROMETRY, INTERACTION WITH GRK5.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	Y08756 mRNA. Translation: CAA70002.1. Y12505 mRNA. Translation: CAA73107.1. Y12506 mRNA. Translation: CAA73108.1. Y12507 mRNA. Translation: CAA73109.1. Y10437 mRNA. Translation: CAA71462.1. Y13584 mRNA. Translation: CAA73911.1. Y09586 mRNA. Translation: CAA70774.1. AJ011371 mRNA. Translation: CAA09600.1. AJ278979 mRNA. Translation: CAC22248.1. AJ278981 mRNA. Translation: CAC22250.1. AJ278982 mRNA. Translation: CAC22251.1. BC074755 mRNA. Translation: AAH74755.1. AJ243213 Genomic DNA. Translation: CAB71316.1. Z48150 mRNA. Translation: CAA88167.1.
IPI	IPI00014378. IPI00064638. IPI00186777. IPI00216427. IPI00216428. IPI00216429. IPI00291659.
PIR	S66493.
RefSeq	NP_000861.1. NM_000870.5. NP_001035259.1. NM_001040169.2. NP_001035262.2. NM_001040172.2. NP_955525.1. NM_199453.3.
UniGene	Hs.483773.
3D structure databases
ProteinModelPortal	Q13639.
SMR	Q13639. Positions 12-327.
ModBase	Search...
Protein-protein interaction databases
MINT	MINT-1347413.
STRING	Q13639.
Protein family/group databases
GPCRDB	Search...
Polymorphism databases
DMDM	12644029.
Proteomic databases
PRIDE	Q13639.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000377888; ENSP00000367120; ENSG00000164270.
GeneID	3360.
KEGG	hsa:3360.
UCSC	uc003lpj.1. human. uc003lpk.1. human. uc003lpl.1. human. uc003lpn.1. human. uc003lpo.1. human.
Organism-specific databases
CTD	3360.
GeneCards	GC05M142977.
HGNC	HGNC:5299. HTR4.
MIM	602164. gene.
neXtProt	NX_Q13639.
PharmGKB	PA29557.
GenAtlas	Search...
Phylogenomic databases
eggNOG	prNOG13487.
HOVERGEN	HBG106962.
OrthoDB	EOG4933HZ.
Enzyme and pathway databases
Reactome	REACT_111102. Signal Transduction.
Gene expression databases
ArrayExpress	Q13639.
Bgee	Q13639.
Genevestigator	Q13639.
GermOnline	ENSG00000164270. Homo sapiens.
Family and domain databases
InterPro	IPR001520. 5HT4_rcpt. IPR000276. 7TM_GPCR_Rhodpsn. IPR017452. GPCR_Rhodpsn_supfam. [Graphical view]
KO	K04160.
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
DrugBank	DB00604. Cisapride. DB00953. Rizatriptan. DB01079. Tegaserod. DB00315. Zolmitriptan.
NextBio	13288.
SOURCE	Search...

Entry information

Entry name

5HT4R_HUMAN

Accession

Primary (citable) accession number: Q13639
Secondary accession number(s): Q96KH9 expand/collapse secondary AC list

Q9UQR6

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 1, 1997
Last sequence update:	January 11, 2001
Last modified:	December 14, 2011
This is version 112 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

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List of 7-transmembrane G-linked receptor entries

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Human chromosome 5: entries, gene names and cross-references to MIM

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

SIMILARITY comments

Index of protein domains and families

Dec	JAN	Feb
	04
2011	2012	2013

Preferred order of sections

Names and origin

Protein attributes

General annotation (Comments)

Ontologies

Alternative products

Sequence annotation (Features)

Molecule processing

Regions

Amino acid modifications

Natural variations

Sequences

References

Cross-references

Sequence databases

3D structure databases

Protein-protein interaction databases

Protein family/group databases

Polymorphism databases

Proteomic databases

Protocols and materials databases

Genome annotation databases

Organism-specific databases

Phylogenomic databases

Enzyme and pathway databases

Gene expression databases

Family and domain databases

Other

Entry information

Relevant documents