Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTIWF1R5)

• DOT Name: 5-hydroxytryptamine receptor 3E (HTR3E)
• Synonyms: 5-HT3-E; 5-HT3E; Serotonin receptor 3E
• Gene Name: HTR3E
• Related Disease:
  Irritable bowel syndrome
  Obsessive compulsive disorder
  Schizophrenia
• UniProt ID: 5HT3E_HUMAN
• Pfam ID: PF02931 ; PF02932
• Sequence:
  MEGSWFHRKRFSFYLLLGFLLQGRGVTFTINCSGFGQHGADPTALNSVFNRKPFRPVTNI
  SVPTQVNISFAMSAILDVNEQLHLLSSFLWLEMVWDNPFISWNPEECEGITKMSMAAKNL
  WLPDIFIIELMDVDKTPKGLTAYVSNEGRIRYKKPMKVDSICNLDIFYFPFDQQNCTLTF
  SSFLYTVDSMLLDMEKEVWEITDASRNILQTHGEWELLGLSKATAKLSRGGNLYDQIVFY
  VAIRRRPSLYVINLLVPSGFLVAIDALSFYLPVKSGNRVPFKITLLLGYNVFLLMMSDLL
  PTSGTPLIGVYFALCLSLMVGSLLETIFITHLLHVATTQPPPLPRWLHSLLLHCNSPGRC
  CPTAPQKENKGPGLTPTHLPGVKEPEVSAGQMPGPAEAELTGGSEWTRAQREHEAQKQHS
  VELWLQFSHAMDAMLFRLYLLFMASSIITVICLWNT
• Function: Forms serotonin (5-hydroxytryptamine/5-HT3)-activated cation-selective channel complexes, which when activated cause fast, depolarizing responses in neurons.
• Tissue Specificity: Expressed in adult colon and intestine.
• KEGG Pathway:
  Serotonergic sy.pse (hsa04726)
  Taste transduction (hsa04742)
• Reactome Pathway: Neurotransmitter receptors and postsynaptic signal transmission (R-HSA-112314)

Molecular Interaction Atlas (MIA) of This DOT

3 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Irritable bowel syndrome	DIS27206	Strong	Biomarker	[1]
Obsessive compulsive disorder	DIS1ZMM2	Strong	Genetic Variation	[2]
Schizophrenia	DISSRV2N	moderate	Genetic Variation	[3]

1 Drug(s) Affected the Gene/Protein Processing of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of 5-hydroxytryptamine receptor 3E (HTR3E).	[4]

1 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of 5-hydroxytryptamine receptor 3E (HTR3E).	[5]

References

• [1] First evidence for an association of a functional variant in the microRNA-510 target site of the serotonin receptor-type 3E gene with diarrhea predominant irritable bowel syndrome.Hum Mol Genet. 2008 Oct 1;17(19):2967-77. doi: 10.1093/hmg/ddn195. Epub 2008 Jul 9.
• [2] 5-HT3 receptor influences the washing phenotype and visual organization in obsessive-compulsive disorder supporting 5-HT3 receptor antagonists as novel treatment option.Eur Neuropsychopharmacol. 2014 Jan;24(1):86-94. doi: 10.1016/j.euroneuro.2013.07.003. Epub 2013 Aug 6.
• [3] A coding variant of the novel serotonin receptor subunit 5-HT3E influences sustained attention in schizophrenia patients.Eur Neuropsychopharmacol. 2010 Jun;20(6):414-20. doi: 10.1016/j.euroneuro.2010.02.012. Epub 2010 Mar 30.
• [4] 17-Estradiol Activates HSF1 via MAPK Signaling in ER-Positive Breast Cancer Cells. Cancers (Basel). 2019 Oct 11;11(10):1533. doi: 10.3390/cancers11101533.
• [5] Air pollution and DNA methylation alterations in lung cancer: A systematic and comparative study. Oncotarget. 2017 Jan 3;8(1):1369-1391. doi: 10.18632/oncotarget.13622.