Human Gene HTR4 (ENST00000521530.5)
  Description: Homo sapiens 5-hydroxytryptamine receptor 4 (HTR4), transcript variant a, mRNA. (from RefSeq NM_001040169)
RefSeq Summary (NM_001040169): This gene is a member of the family of serotonin receptors, which are G protein coupled receptors that stimulate cAMP production in response to serotonin (5-hydroxytryptamine). The gene product is a glycosylated transmembrane protein that functions in both the peripheral and central nervous system to modulate the release of various neurotransmitters. Multiple transcript variants encoding proteins with distinct C-terminal sequences have been described. [provided by RefSeq, May 2010].
Gencode Transcript: ENST00000521530.5
Gencode Gene: ENSG00000164270.18
Transcript (Including UTRs)
   Position: hg38 chr5:148,451,032-148,637,020 Size: 185,989 Total Exon Count: 6 Strand: -
Coding Region
   Position: hg38 chr5:148,451,185-148,637,014 Size: 185,830 Coding Exon Count: 6 

Page IndexSequence and LinksUniProtKB CommentsMalaCardsCTDRNA-Seq Expression
Microarray ExpressionRNA StructureProtein StructureOther SpeciesGO AnnotationsmRNA Descriptions
PathwaysOther NamesMethods
Data last updated at UCSC: 2021-01-14 15:32:12

-  Sequence and Links to Tools and Databases
Genomic Sequence (chr5:148,451,032-148,637,020)mRNA (may differ from genome)Protein (387 aa)
Gene SorterGenome BrowserOther Species FASTAGene interactionsTable SchemaBioGPS
CGAPEnsemblEntrez GeneExonPrimerGeneCardsHGNC

-  Comments and Description Text from UniProtKB
DESCRIPTION: RecName: Full=5-hydroxytryptamine receptor 4; Short=5-HT-4; Short=5-HT4; AltName: Full=Serotonin receptor 4;
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: 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).
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.
SIMILARITY: Belongs to the G-protein coupled receptor 1 family.

-  MalaCards Disease Associations
  MalaCards Gene Search: HTR4
Diseases sorted by gene-association score: constipation (4), irritable bowel syndrome (4), gastrointestinal system disease (4), colonic pseudo-obstruction (3), pylorospasm (2), stomach disease (2), functional colonic disease (1), intestinal disease (1), phototoxic dermatitis (1), functional diarrhea (1), pituitary-dependent cushing's disease (1)

-  Comparative Toxicogenomics Database (CTD)
  The following chemicals interact with this gene
  • C082871 GR 113808
  • C107826 RS 67333
  • D014635 Valproic Acid
  • C105050 tegaserod
  • C070187 (endo-N-8-methyl-8-azabicyclo(3.2.1)oct-3-yl)-2,3-dihydro-3-ethyl-2-oxo-1H-benzimidazol-1-carboxamide
  • C049325 1,2-dithiol-3-thione
  • C072790 2-methoxy-4-amino-5-chlorobenzoic acid 2-(diethylamino)ethyl ester
  • C117947 2-piperidinoethyl 4-amino-5-chloro-2-methoxybenzoate
  • D001564 Benzo(a)pyrene
  • D002220 Carbamazepine
          more ... click here to view the complete list

-  RNA-Seq Expression Data from GTEx (53 Tissues, 570 Donors)
  Highest median expression: 1.86 RPKM in Small Intestine - Terminal Ileum
Total median expression: 7.63 RPKM

View in GTEx track of Genome Browser    View at GTEx portal     View GTEx Body Map

+  Microarray Expression Data
  Press "+" in the title bar above to open this section.

-  mRNA Secondary Structure of 3' and 5' UTRs
RegionFold EnergyBasesEnergy/Base
Display As
3' UTR -43.00153-0.281 Picture PostScript Text

The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.

-  Protein Domain and Structure Information
  InterPro Domains: Graphical view of domain structure
IPR001520 - 5HT4_rcpt
IPR000276 - 7TM_GPCR_Rhodpsn
IPR017452 - GPCR_Rhodpsn_supfam

Pfam Domains:
PF00001 - 7 transmembrane receptor (rhodopsin family)

ModBase Predicted Comparative 3D Structure on Q13639
The pictures above may be empty if there is no ModBase structure for the protein. The ModBase structure frequently covers just a fragment of the protein. You may be asked to log onto ModBase the first time you click on the pictures. It is simplest after logging in to just click on the picture again to get to the specific info on that model.

-  Orthologous Genes in Other Species
  Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
MouseRatZebrafishD. melanogasterC. elegansS. cerevisiae
Genome BrowserGenome BrowserNo orthologNo orthologNo orthologNo ortholog
Gene Details     
Gene Sorter     
Protein SequenceProtein Sequence    

-  Gene Ontology (GO) Annotations with Structured Vocabulary
  Molecular Function:
GO:0004871 signal transducer activity
GO:0004930 G-protein coupled receptor activity
GO:0004993 G-protein coupled serotonin receptor activity
GO:0001594 trace-amine receptor activity

Biological Process:
GO:0007165 signal transduction
GO:0007186 G-protein coupled receptor signaling pathway
GO:0007187 G-protein coupled receptor signaling pathway, coupled to cyclic nucleotide second messenger
GO:0007214 gamma-aminobutyric acid signaling pathway
GO:0007268 chemical synaptic transmission
GO:0032098 regulation of appetite

Cellular Component:
GO:0005737 cytoplasm
GO:0005768 endosome
GO:0005886 plasma membrane
GO:0005887 integral component of plasma membrane
GO:0016020 membrane
GO:0016021 integral component of membrane

-  Descriptions from all associated GenBank mRNAs
  AB070620 - Homo sapiens HTR4 mRNA for 5-hydroxytryptamine 4 receptor, partial cds.
Y08756 - H.sapiens mRNA for serotonin receptor 5-HT4.
AJ278979 - Homo sapiens mRNA for 5-hydroxytryptamine4 receptor (HTR4 gene), splice variant h5-HT4(a).
AJ278981 - Homo sapiens mRNA for 5-hydroxytryptamine4 receptor (HTR4 gene), splice variant h5-HT4(g).
AJ633645 - Homo sapiens mRNA for 5-hydroxytryptamine 4 receptor isoform g2 (HTR4 gene).
AJ131725 - Homo sapiens mRNA for serotonin receptor 5-HT4 (splice variant h5-HT4(g).
Y13584 - Homo sapiens mRNA for serotin receptor 4, short splice variant.
AJ011371 - Homo sapiens mRNA for serotonin 4 receptor, splice variant h5-HT4(e).
Y09586 - Homo sapiens mRNA for serotonin 4 receptor (h5-HT4(a)), splice variant.
Y12507 - H.sapiens mRNA for serotonin receptor 5-HT4D, splice variant.
AM712912 - Homo sapiens mRNA for 5-hydroxytryptamine (serotonin) receptor 4 (HTR4 gene), isoform C.
AJ131724 - Homo sapiens mRNA for serotonin receptor 5-HT4 (splice variant h5-HT4(b)).
MF775735 - Homo sapiens 5-hydroxytryptamine receptor 4 transcript variant b2 (HTR4) mRNA, complete cds, alternatively spliced.
MF775736 - Homo sapiens 5-hydroxytryptamine receptor 4 transcript variant b3 (HTR4) mRNA, complete cds, alternatively spliced.
Y12506 - H.sapiens mRNA for serotonin receptor 5-HT4C, splice variant.
AK308471 - Homo sapiens cDNA, FLJ98512.
AJ131726 - Homo sapiens mRNA for serotonin receptor 5-HT4 (splice variant h5-HT4(i)).
Y12505 - H.sapiens mRNA for serotonin receptor 5-HT4B, splice variant.
AJ278980 - Homo sapiens mRNA for 5-hydroxytryptamine4 receptor (HTR4 gene), splice variant h5-HT4(b).
AJ519673 - Homo sapiens mRNA for 5-hydroxytryptamine 4 receptor subunit b (HTR4B gene).
BC074755 - Homo sapiens 5-hydroxytryptamine (serotonin) receptor 4, mRNA (cDNA clone MGC:103832 IMAGE:30915214), complete cds.
BC095497 - Homo sapiens 5-hydroxytryptamine (serotonin) receptor 4, mRNA (cDNA clone MGC:111700 IMAGE:6971934), complete cds.
Y10437 - H.sapiens mRNA for serotonin receptor 4.
AJ278982 - Homo sapiens mRNA for 5-hydroxytryptamine4 receptor (HTR4 gene), splice variant h5-HT4(n).
AK095223 - Homo sapiens cDNA FLJ37904 fis, clone COLON2000557.
Z48150 - H.sapiens 5-HT4 mRNA for serotonin 4 receptor (5-HT4).

-  Biochemical and Signaling Pathways
  KEGG - Kyoto Encyclopedia of Genes and Genomes
hsa04020 - Calcium signaling pathway
hsa04080 - Neuroactive ligand-receptor interaction

Reactome (by CSHL, EBI, and GO)

Protein Q13639 (Reactome details) participates in the following event(s):

R-HSA-390931 5-HT4, 6 and 7 receptors can bind serotonin
R-HSA-744886 The Ligand:GPCR:Gs complex dissociates
R-HSA-744887 Liganded Gs-activating GPCRs bind inactive heterotrimeric Gs
R-HSA-379044 Liganded Gs-activating GPCR acts as a GEF for Gs
R-HSA-390666 Serotonin receptors
R-HSA-418555 G alpha (s) signalling events
R-HSA-375280 Amine ligand-binding receptors
R-HSA-388396 GPCR downstream signalling
R-HSA-373076 Class A/1 (Rhodopsin-like receptors)
R-HSA-372790 Signaling by GPCR
R-HSA-500792 GPCR ligand binding
R-HSA-162582 Signal Transduction

-  Other Names for This Gene
  Alternate Gene Symbols: 5HT4R_HUMAN, ENST00000521530.1, ENST00000521530.2, ENST00000521530.3, ENST00000521530.4, NM_001040169, Q13639, Q546Q1, Q684M0, Q712M9, Q96KH9, Q96KI0, Q9H199, Q9NY73, Q9UBM6, Q9UBT4, Q9UE22, Q9UE23, Q9UQR6, uc021yfh.1, uc021yfh.2
UCSC ID: ENST00000521530.5
RefSeq Accession: NM_001040169
Protein: Q13639 (aka 5HT4R_HUMAN or 5H4_HUMAN)
CCDS: CCDS34270.1

-  Methods, Credits, and Use Restrictions
  Click here for details on how this gene model was made and data restrictions if any.