HTR4
5-hydroxytryptamine receptor 4
Also known as: 5-HT4, 5HT4R_HUMAN
Cross-references: UniProt · Ensembl · Human Protein Atlas · GeneCards · NCBI Gene
Protein identityUniProt · HPA
- UniProt accession
- Q13639
- Gene
- HTR4
- Ensembl
- ENSG00000164270
- Chromosome
- 5
- Canonical length
- 388 aa
- Protein class
- FDA approved drug targets, G-protein coupled receptors, Predicted intracellular proteins, Predicted membrane proteins, Transporters
OverviewNCBI Gene
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]
Canonical amino-acid sequenceUniProt
388 residues, UniProt reviewed canonical sequence.
>Q13639|HTR4
1 MDKLDANVSS EEGFGSVEKV VLLTFLSTVI LMAILGNLLV MVAVCWDRQL RKIKTNYFIV
61 SLAFADLLVS VLVMPFGAIE LVQDIWIYGE VFCLVRTSLD VLLTTASIFH LCCISLDRYY
121 AICCQPLVYR NKMTPLRIAL MLGGCWVIPT FISFLPIMQG WNNIGIIDLI EKRKFNQNSN
181 STYCVFMVNK PYAITCSVVA FYIPFLLMVL AYYRIYVTAK EHAHQIQMLQ RAGASSESRP
241 QSADQHSTHR MRTETKAAKT LCIIMGCFCL CWAPFFVTNI VDPFIDYTVP GQVWTAFLWL
301 GYINSGLNPF LYAFLNKSFR RAFLIILCCD DERYRRPSIL GQTVPCSTTT INGSTHVLRD
361 AVECGGQWES QCHPPATSPL VAAQPSDTLocalizationUniProt · AlphaFold · HPA
Whether an antibody against HTR4 can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.
- Antibody reachability
- Cell surface
- Secreted
- No
- Transmembrane segments
- 7
- Mean surface accessibility (rSASA)
- 0.36
- Highest tissue expression
- 8.5 nTPM
Expression across tissuesHPA
Tissue
- small intestine: 8.5 nTPM
- duodenum: 4.7 nTPM
- heart muscle: 4.3 nTPM
- rectum: 2.5 nTPM
- colon: 2.4 nTPM
- basal ganglia: 2.1 nTPM
Single-cell type
- cardiomyocytes: 359 nCPM
- brain inhibitory neurons: 188 nCPM
- paneth cells: 170 nCPM
- enteric stem cells: 131 nCPM
- lactotrophs: 117 nCPM
- enterocytes: 99 nCPM
Immune cell
- T-reg: 0.1 nTPM
- basophil: 0 nTPM
- classical monocyte: 0 nTPM
- eosinophil: 0 nTPM
- gdT-cell: 0 nTPM
- intermediate monocyte: 0 nTPM
Brain region
- basal ganglia: 29 nTPM
- hippocampal formation: 20 nTPM
- cerebral cortex: 12 nTPM
- hypothalamus: 9.4 nTPM
- amygdala: 7.3 nTPM
- midbrain: 5.6 nTPM
ReferencesPubMed · IEDB
Publications for HTR4 from three distinct lines of evidence, kept separate because they answer different questions: whether antibodies are directed at the protein, whether a B-cell epitope has been mapped on it, and whether a T-cell epitope has. Each is labelled with its source.
Reference: AutoantibodyPubMed
2 publications
- 5-hydroxytryptamine receptors in the human cardiovascular system.
2006 · Pharmacol Ther · RCR 7.3 · 256 citations - Immunomodulation by maternal autoantibodies of the fetal serotoninergic 5-HT4 receptor and its consequences in early BALB/c mouse embryonic development.
2007 · BMC Dev Biol · RCR 0.3 · 11 citations
Sources: PubMed — antigen-level antibody evidence from a custom retrieval. Records matching a controlled set of autoantibody terms (the MeSH descriptors Autoantibodies and Autoantigens, with title and abstract term variants) were obtained through NCBI E-utilities, and their titles and abstracts parsed for constructions that direct an antibody at a named protein rather than for co-occurrence. Captured names were resolved against UniProt nomenclature and each antigen adjudicated individually against the source text. Bibliographic records from PubMed and MeSH, U.S. National Library of Medicine; citation metrics from NIH iCite (Hutchins et al., PLoS Biology 2016). Titles link to PubMed; abstracts are not reproduced here. The NLM does not endorse this analysis.
Genetic constraint and essentialitygnomAD · DepMap
Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.
- gnomAD LOEUF (loss-of-function intolerance)
- 0.65
- gnomAD pLI
- 0.02
- gnomAD missense Z
- 0.7
- DepMap mean gene effect
- 0.05
- DepMap dependency class
- none
Cancer expressionTCGA
Across TCGA tumor cohorts, this protein is over-expressed in roughly 4% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).
OntologyGO
Biological processes
- adenylate cyclase-activating G protein-coupled receptor signaling pathway
- adenylate cyclase-activating serotonin receptor signaling pathway
- adenylate cyclase-inhibiting serotonin receptor signaling pathway
- chemical synaptic transmission
- G protein-coupled receptor signaling pathway
- G protein-coupled receptor signaling pathway, coupled to cyclic nucleotide second messenger
- maintenance of gastrointestinal epithelium
- mucus secretion
- regulation of appetite
- regulation of postsynapse assembly
- large intestinal transit
Molecular functions
- G protein-coupled serotonin receptor activity
- neurotransmitter receptor activity
- serotonin binding
- serotonin receptor activity
Cellular components
Protein domainsUniProt · Pfam · InterPro
- G protein-coupled receptor, rhodopsin-like
- GPCR, rhodopsin-like, 7TM
- 7 transmembrane receptor (rhodopsin family)
- 5-Hydroxytryptamine 4 receptor
KeywordsUniProt
InteractionsUniProt · HPA
Protein binding partners of HTR4 in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.
Antibody and autoantibody relevanceSeroatlas analysis
Seroatlas reads HTR4 as an antibody target. Whether an autoantibody or antibody against HTR4 could matter depends on whether native HTR4 is physically reachable, whether the body needs it intact, and whether it acts in a disease-relevant tissue.
HTR4 is annotated at the cell surface, where native HTR4 is exposed to circulating antibodies and is a prime autoantibody target that could block, deplete, or overstimulate it.
Annotation status
The present source text does not explicitly label HTR4 as an autoantigen. Seroatlas presents hypothesis context only and does not manufacture a known-serology claim.
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