UniProtKB - Q13639 (5HT4R_HUMAN)
5-hydroxytryptamine receptor 4
HTR4
Functioni
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.
GO - Molecular functioni
- G protein-coupled serotonin receptor activity Source: MGI
- neurotransmitter receptor activity Source: GO_Central
- serotonin binding Source: GO_Central
GO - Biological processi
- adenylate cyclase-inhibiting serotonin receptor signaling pathway Source: GO_Central
- chemical synaptic transmission Source: GO_Central
- G protein-coupled receptor signaling pathway Source: ProtInc
- G protein-coupled receptor signaling pathway, coupled to cyclic nucleotide second messenger Source: GO_Central
- regulation of appetite Source: InterPro
Keywordsi
Molecular function | G-protein coupled receptor, Receptor, Transducer |
Enzyme and pathway databases
PathwayCommonsi | Q13639 |
Reactomei | R-HSA-390666, Serotonin receptors R-HSA-418555, G alpha (s) signalling events R-HSA-9660821, ADORA2B mediated anti-inflammatory cytokines production |
SignaLinki | Q13639 |
SIGNORi | Q13639 |
Protein family/group databases
TCDBi | 9.A.14.3.18, the g-protein-coupled receptor (gpcr) family |
Names & Taxonomyi
Protein namesi | Recommended name: 5-hydroxytryptamine receptor 4Short name: 5-HT-4 Short name: 5-HT4 Alternative name(s): Serotonin receptor 4 |
Gene namesi | Name:HTR4 |
Organismi | Homo sapiens (Human) |
Taxonomic identifieri | 9606 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Proteomesi |
|
Organism-specific databases
HGNCi | HGNC:5299, HTR4 |
MIMi | 602164, gene |
neXtProti | NX_Q13639 |
VEuPathDBi | HostDB:ENSG00000164270 |
Subcellular locationi
Plasma membrane
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
Endosome
- endosome Source: UniProtKB-SubCell
Plasma Membrane
- integral component of plasma membrane Source: GO_Central
- plasma membrane Source: Reactome
Other locations
Topology
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Topological domaini | 1 – 19 | ExtracellularBy similarityAdd BLAST | 19 | |
Transmembranei | 20 – 40 | Helical; Name=1By similarityAdd BLAST | 21 | |
Topological domaini | 41 – 58 | CytoplasmicBy similarityAdd BLAST | 18 | |
Transmembranei | 59 – 79 | Helical; Name=2By similarityAdd BLAST | 21 | |
Topological domaini | 80 – 93 | ExtracellularBy similarityAdd BLAST | 14 | |
Transmembranei | 94 – 116 | Helical; Name=3By similarityAdd BLAST | 23 | |
Topological domaini | 117 – 137 | CytoplasmicBy similarityAdd BLAST | 21 | |
Transmembranei | 138 – 158 | Helical; Name=4By similarityAdd BLAST | 21 | |
Topological domaini | 159 – 192 | ExtracellularBy similarityAdd BLAST | 34 | |
Transmembranei | 193 – 213 | Helical; Name=5By similarityAdd BLAST | 21 | |
Topological domaini | 214 – 260 | CytoplasmicBy similarityAdd BLAST | 47 | |
Transmembranei | 261 – 281 | Helical; Name=6By similarityAdd BLAST | 21 | |
Topological domaini | 282 – 294 | ExtracellularBy similarityAdd BLAST | 13 | |
Transmembranei | 295 – 315 | Helical; Name=7By similarityAdd BLAST | 21 | |
Topological domaini | 316 – 388 | CytoplasmicBy similarityAdd BLAST | 73 |
Keywords - Cellular componenti
Cell membrane, Endosome, MembranePathology & Biotechi
Organism-specific databases
DisGeNETi | 3360 |
OpenTargetsi | ENSG00000164270 |
PharmGKBi | PA29557 |
Miscellaneous databases
Pharosi | Q13639, Tclin |
Chemistry databases
ChEMBLi | CHEMBL1875 |
DrugBanki | DB01239, Chlorprothixene DB08810, Cinitapride DB00604, Cisapride DB11273, Dihydroergocornine DB13345, Dihydroergocristine DB00320, Dihydroergotamine DB01049, Ergoloid mesylate DB12141, Gilteritinib DB01233, Metoclopramide DB05542, Naronapride DB00904, Ondansetron DB00715, Paroxetine DB04873, Piboserod DB06480, Prucalopride DB04917, Renzapride DB09304, Setiptiline DB05905, TD-2749 DB01079, Tegaserod DB13025, Tiapride DB06422, Ticalopride DB12702, Velusetrag |
DrugCentrali | Q13639 |
GuidetoPHARMACOLOGYi | 9 |
Genetic variation databases
BioMutai | HTR4 |
DMDMi | 12644029 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000068965 | 1 – 388 | 5-hydroxytryptamine receptor 4Add BLAST | 388 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Glycosylationi | 7 | N-linked (GlcNAc...) asparagineSequence analysis | 1 | |
Disulfide bondi | 93 ↔ 184 | PROSITE-ProRule annotation | ||
Lipidationi | 329 | S-palmitoyl cysteineBy similarity | 1 |
Keywords - PTMi
Disulfide bond, Glycoprotein, Lipoprotein, PalmitateProteomic databases
PeptideAtlasi | Q13639 |
PRIDEi | Q13639 |
PTM databases
GlyGeni | Q13639, 1 site |
iPTMneti | Q13639 |
PhosphoSitePlusi | Q13639 |
SwissPalmi | Q13639 |
Expressioni
Tissue specificityi
Gene expression databases
Bgeei | ENSG00000164270, Expressed in epithelium of bronchus and 217 other tissues |
ExpressionAtlasi | Q13639, baseline and differential |
Genevisiblei | Q13639, HS |
Organism-specific databases
HPAi | ENSG00000164270, Group enriched (brain, heart muscle, intestine) |
Interactioni
Subunit structurei
Isoform 5-HT4(A) interacts with MAGI2, MPP3, SLC9A3R1 and SNX27 isoforms 1 and 2. Isoform 5-HT4(E) interacts with PATJ, 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).
By similarity1 PublicationBinary interactionsi
Protein-protein interaction databases
BioGRIDi | 109592, 17 interactors |
IntActi | Q13639, 17 interactors |
MINTi | Q13639 |
STRINGi | 9606.ENSP00000353915 |
Chemistry databases
BindingDBi | Q13639 |
Miscellaneous databases
RNActi | Q13639, protein |
Structurei
Secondary structure
3D structure databases
AlphaFoldDBi | Q13639 |
SMRi | Q13639 |
ModBasei | Search... |
PDBe-KBi | Search... |
Family & Domainsi
Sequence similaritiesi
Keywords - Domaini
Transmembrane, Transmembrane helixPhylogenomic databases
eggNOGi | KOG3656, Eukaryota |
GeneTreei | ENSGT00940000155983 |
HOGENOMi | CLU_009579_11_0_1 |
InParanoidi | Q13639 |
OMAi | AHQIRIL |
OrthoDBi | 750855at2759 |
PhylomeDBi | Q13639 |
TreeFami | TF316350 |
Family and domain databases
InterProi | View protein in InterPro IPR001520, 5HT4_rcpt IPR000276, GPCR_Rhodpsn IPR017452, GPCR_Rhodpsn_7TM |
Pfami | View protein in Pfam PF00001, 7tm_1, 1 hit |
PRINTSi | PR01059, 5HT4RECEPTR PR00237, GPCRRHODOPSN |
SMARTi | View protein in SMART SM01381, 7TM_GPCR_Srsx, 1 hit |
PROSITEi | View protein in PROSITE PS00237, G_PROTEIN_RECEP_F1_1, 1 hit PS50262, G_PROTEIN_RECEP_F1_2, 1 hit |
s (9+)i Sequence
Sequence statusi: Complete.
This entry describes 9 produced by isoformsialternative splicing. AlignAdd to basketThis entry has 9 described isoforms and 2 potential isoforms that are computationally mapped.Show allAlign All
This isoform has been chosen as the sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry. canonicali
10 20 30 40 50
MDKLDANVSS EEGFGSVEKV VLLTFLSTVI LMAILGNLLV MVAVCWDRQL
60 70 80 90 100
RKIKTNYFIV SLAFADLLVS VLVMPFGAIE LVQDIWIYGE VFCLVRTSLD
110 120 130 140 150
VLLTTASIFH LCCISLDRYY AICCQPLVYR NKMTPLRIAL MLGGCWVIPT
160 170 180 190 200
FISFLPIMQG WNNIGIIDLI EKRKFNQNSN STYCVFMVNK PYAITCSVVA
210 220 230 240 250
FYIPFLLMVL AYYRIYVTAK EHAHQIQMLQ RAGASSESRP QSADQHSTHR
260 270 280 290 300
MRTETKAAKT LCIIMGCFCL CWAPFFVTNI VDPFIDYTVP GQVWTAFLWL
310 320 330 340 350
GYINSGLNPF LYAFLNKSFR RAFLIILCCD DERYRRPSIL GQTVPCSTTT
360 370 380
INGSTHVLRD AVECGGQWES QCHPPATSPL VAAQPSDT
The sequence of this isoform differs from the canonical sequence as follows:
360-388: DAVECGGQWESQCHPPATSPLVAAQPSDT → YTVLHRGHHQELEKLPIHNDPESLESCF
The sequence of this isoform differs from the canonical sequence as follows:
360-388: DAVECGGQWESQCHPPATSPLVAAQPSDT → F
The sequence of this isoform differs from the canonical sequence as follows:
359-388: RDAVECGGQWESQCHPPATSPLVAAQPSDT → SSGTETDRRNFGIRKRRLTKPS
The sequence of this isoform differs from the canonical sequence as follows:
359-388: RDAVECGGQWESQCHPPATSPLVAAQPSDT → SGCSPVSSFLLLFCNRPVPV
The sequence of this isoform differs from the canonical sequence as follows:
169-169: L → LERSLNQGLGQDFHA
The sequence of this isoform differs from the canonical sequence as follows:
360-388: Missing.
The sequence of this isoform differs from the canonical sequence as follows:
359-359: R → RTDFLFDRDILARYWTKPARAGPFSGTLSIRCLTARKPVLG
The sequence of this isoform differs from the canonical sequence as follows:
359-388: RDAVECGGQWESQCHPPATSPLVAAQPSDT → SSGTETDRKK...GRKSCFREGK
Computationally mapped potential isoform sequencesi
There are 2 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basketE5RK45 | E5RK45_HUMAN | 5-hydroxytryptamine receptor 4 | HTR4 | 371 | Annotation score: | ||
E5RHV8 | E5RHV8_HUMAN | 5-hydroxytryptamine receptor 4 | HTR4 | 87 | Annotation score: |
Natural variant
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_067412 | 27 | S → L in a patient with diffuse leukoencephalopathy with spheroids; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs199508638Ensembl. | 1 | |
Natural variantiVAR_049364 | 372 | C → Y. Corresponds to variant dbSNP:rs34826744EnsemblClinVar. | 1 |
Alternative sequence
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Alternative sequenceiVSP_001845 | 169 | L → LERSLNQGLGQDFHA in isoform 5-HT4(F). Curated | 1 | |
Alternative sequenceiVSP_001847 | 359 – 388 | RDAVE…QPSDT → SSGTETDRRNFGIRKRRLTK PS in isoform 5-HT4(D). CuratedAdd BLAST | 30 | |
Alternative sequenceiVSP_001846 | 359 – 388 | RDAVE…QPSDT → SGCSPVSSFLLLFCNRPVPV in isoform 5-HT4(E). CuratedAdd BLAST | 30 | |
Alternative sequenceiVSP_047862 | 359 – 388 | RDAVE…QPSDT → SSGTETDRKKLWNKEEKIDQ TIQMPKRKRKKKASLSYEDL ILLGRKSCFREGK in isoform 5-HT4c1. 1 PublicationAdd BLAST | 30 | |
Alternative sequenceiVSP_043316 | 359 | R → RTDFLFDRDILARYWTKPAR AGPFSGTLSIRCLTARKPVL G in isoform 5-HT4(I). Curated | 1 | |
Alternative sequenceiVSP_001849 | 360 – 388 | DAVEC…QPSDT → YTVLHRGHHQELEKLPIHND PESLESCF in isoform 5-HT4(A). CuratedAdd BLAST | 29 | |
Alternative sequenceiVSP_001848 | 360 – 388 | DAVEC…QPSDT → F in isoform 5-HT4(C). CuratedAdd BLAST | 29 | |
Alternative sequenceiVSP_001850 | 360 – 388 | Missing in isoform 5-HT4(G). CuratedAdd BLAST | 29 |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | 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 AJ131724 mRNA Translation: CAC20411.1 AJ011371 mRNA Translation: CAA09600.1 AJ278979 mRNA Translation: CAC22248.1 AJ278980 mRNA Translation: CAC22249.1 AJ278981 mRNA Translation: CAC22250.1 AJ278982 mRNA Translation: CAC22251.1 AJ131725 mRNA Translation: CAC79533.1 AJ131726 mRNA Translation: CAC79538.1 AJ633645 mRNA Translation: CAG17627.1 AM712912 mRNA Translation: CAN84676.1 AC008627 Genomic DNA No translation available. AC011390 Genomic DNA No translation available. AC091971 Genomic DNA No translation available. AC114939 Genomic DNA No translation available. CH471062 Genomic DNA Translation: EAW61800.1 CH471062 Genomic DNA Translation: EAW61801.1 CH471062 Genomic DNA Translation: EAW61804.1 BC074755 mRNA Translation: AAH74755.1 BC095497 mRNA Translation: AAH95497.1 AJ243213 Genomic DNA Translation: CAB71316.1 Z48150 mRNA Translation: CAA88167.1 |
CCDSi | CCDS34270.1 [Q13639-2] CCDS34271.1 [Q13639-5] CCDS34272.1 [Q13639-8] CCDS34273.2 [Q13639-3] CCDS4291.1 [Q13639-1] CCDS75353.1 [Q13639-9] |
PIRi | S66493 |
RefSeqi | NP_000861.1, NM_000870.6 [Q13639-1] NP_001035259.1, NM_001040169.2 [Q13639-2] NP_001035262.2, NM_001040172.2 [Q13639-3] NP_001035263.1, NM_001040173.2 [Q13639-8] NP_001273339.1, NM_001286410.1 [Q13639-9] NP_955525.1, NM_199453.3 [Q13639-5] |
Genome annotation databases
Keywords - Coding sequence diversityi
Alternative splicingSimilar proteinsi
Cross-referencesi
Sequence databases
3D structure databases
Select the link destinations: PDBei RCSB PDBi PDBji Links Updated | PDB entry | Method | Resolution (Å) | Chain | Positions | PDBsum |
5EM9 | X-ray | 1.60 | B | 264-268 | [»] | |
AlphaFoldDBi | Q13639 | |||||
SMRi | Q13639 | |||||
ModBasei | Search... | |||||
PDBe-KBi | Search... |
Protein-protein interaction databases
BioGRIDi | 109592, 17 interactors |
IntActi | Q13639, 17 interactors |
MINTi | Q13639 |
STRINGi | 9606.ENSP00000353915 |
Chemistry databases
BindingDBi | Q13639 |
ChEMBLi | CHEMBL1875 |
DrugBanki | DB01239, Chlorprothixene DB08810, Cinitapride DB00604, Cisapride DB11273, Dihydroergocornine DB13345, Dihydroergocristine DB00320, Dihydroergotamine DB01049, Ergoloid mesylate DB12141, Gilteritinib DB01233, Metoclopramide DB05542, Naronapride DB00904, Ondansetron DB00715, Paroxetine DB04873, Piboserod DB06480, Prucalopride DB04917, Renzapride DB09304, Setiptiline DB05905, TD-2749 DB01079, Tegaserod DB13025, Tiapride DB06422, Ticalopride DB12702, Velusetrag |
DrugCentrali | Q13639 |
GuidetoPHARMACOLOGYi | 9 |
Protein family/group databases
TCDBi | 9.A.14.3.18, the g-protein-coupled receptor (gpcr) family |
GPCRDBi | Search... |
PTM databases
GlyGeni | Q13639, 1 site |
iPTMneti | Q13639 |
PhosphoSitePlusi | Q13639 |
SwissPalmi | Q13639 |
Genetic variation databases
BioMutai | HTR4 |
DMDMi | 12644029 |
Proteomic databases
PeptideAtlasi | Q13639 |
PRIDEi | Q13639 |
Protocols and materials databases
Antibodypediai | 15936, 451 antibodies from 33 providers |
DNASUi | 3360 |
Genome annotation databases
Organism-specific databases
CTDi | 3360 |
DisGeNETi | 3360 |
GeneCardsi | HTR4 |
HGNCi | HGNC:5299, HTR4 |
HPAi | ENSG00000164270, Group enriched (brain, heart muscle, intestine) |
MIMi | 602164, gene |
neXtProti | NX_Q13639 |
OpenTargetsi | ENSG00000164270 |
PharmGKBi | PA29557 |
VEuPathDBi | HostDB:ENSG00000164270 |
GenAtlasi | Search... |
Phylogenomic databases
eggNOGi | KOG3656, Eukaryota |
GeneTreei | ENSGT00940000155983 |
HOGENOMi | CLU_009579_11_0_1 |
InParanoidi | Q13639 |
OMAi | AHQIRIL |
OrthoDBi | 750855at2759 |
PhylomeDBi | Q13639 |
TreeFami | TF316350 |
Enzyme and pathway databases
PathwayCommonsi | Q13639 |
Reactomei | R-HSA-390666, Serotonin receptors R-HSA-418555, G alpha (s) signalling events R-HSA-9660821, ADORA2B mediated anti-inflammatory cytokines production |
SignaLinki | Q13639 |
SIGNORi | Q13639 |
Miscellaneous databases
BioGRID-ORCSi | 3360, 10 hits in 1069 CRISPR screens |
ChiTaRSi | HTR4, human |
GeneWikii | 5-HT4_receptor |
GenomeRNAii | 3360 |
Pharosi | Q13639, Tclin |
PROi | PR:Q13639 |
RNActi | Q13639, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSG00000164270, Expressed in epithelium of bronchus and 217 other tissues |
ExpressionAtlasi | Q13639, baseline and differential |
Genevisiblei | Q13639, HS |
Family and domain databases
InterProi | View protein in InterPro IPR001520, 5HT4_rcpt IPR000276, GPCR_Rhodpsn IPR017452, GPCR_Rhodpsn_7TM |
Pfami | View protein in Pfam PF00001, 7tm_1, 1 hit |
PRINTSi | PR01059, 5HT4RECEPTR PR00237, GPCRRHODOPSN |
SMARTi | View protein in SMART SM01381, 7TM_GPCR_Srsx, 1 hit |
PROSITEi | View protein in PROSITE PS00237, G_PROTEIN_RECEP_F1_1, 1 hit PS50262, G_PROTEIN_RECEP_F1_2, 1 hit |
MobiDBi | Search... |
Entry informationi
Entry namei | 5HT4R_HUMAN | |
Accessioni | Q13639Primary (citable) accession number: Q13639 Secondary accession number(s): C4WYH4 Q9UQR6 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | November 1, 1997 |
Last sequence update: | January 11, 2001 | |
Last modified: | May 25, 2022 | |
This is version 197 of the entry and version 2 of the sequence. See complete history. | ||
Entry statusi | 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. |
Miscellaneousi
Keywords - Technical termi
3D-structure, Reference proteomeDocuments
- 7-transmembrane G-linked receptors
List of 7-transmembrane G-linked receptor entries - Human chromosome 5
Human chromosome 5: entries, gene names and cross-references to MIM - Human entries with genetic variants
List of human entries with genetic variants - Human variants curated from literature reports
Index of human variants curated from literature reports - MIM cross-references
Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot - PDB cross-references
Index of Protein Data Bank (PDB) cross-references - SIMILARITY comments
Index of protein domains and families