Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTQF1R0U)

• DOT Name: Sphingosine 1-phosphate receptor 5 (S1PR5)
• Synonyms: S1P receptor 5; S1P5; Endothelial differentiation G-protein-coupled receptor 8; Sphingosine 1-phosphate receptor Edg-8; S1P receptor Edg-8
• Gene Name: S1PR5
• UniProt ID: S1PR5_HUMAN
• PDB ID: 7EW1; 7YXA
• Pfam ID: PF00001
• Sequence:
  MESGLLRPAPVSEVIVLHYNYTGKLRGARYQPGAGLRADAVVCLAVCAFIVLENLAVLLV
  LGRHPRFHAPMFLLLGSLTLSDLLAGAAYAANILLSGPLTLKLSPALWFAREGGVFVALT
  ASVLSLLAIALERSLTMARRGPAPVSSRGRTLAMAAAAWGVSLLLGLLPALGWNCLGRLD
  ACSTVLPLYAKAYVLFCVLAFVGILAAICALYARIYCQVRANARRLPARPGTAGTTSTRA
  RRKPRSLALLRTLSVVLLAFVACWGPLFLLLLLDVACPARTCPVLLQADPFLGLAMANSL
  LNPIIYTLTNRDLRHALLRLVCCGRHSCGRDPSGSQQSASAAEASGGLRRCLPPGLDGSF
  SGSERSSPQRDGLDTSGSTGSPGAPTAARTLVSEPAAD
• Function: Receptor for the lysosphingolipid sphingosine 1-phosphate (S1P). S1P is a bioactive lysophospholipid that elicits diverse physiological effect on most types of cells and tissues. Is coupled to both the G(i/0)alpha and G(12) subclass of heteromeric G-proteins. May play a regulatory role in the transformation of radial glial cells into astrocytes and may affect proliferative activity of these cells.
• Tissue Specificity: Widely expressed in the brain, most prominently in the corpus callosum, which is predominantly white matter. Detected in spleen, peripheral blood leukocytes, placenta, lung, aorta and fetal spleen. Low-level signal detected in many tissue extracts. Overexpressed in leukemic large granular lymphocytes. Isoform 1 is predominantly expressed in peripheral tissues. Isoform 2 is expressed in brain, spleen and peripheral blood leukocytes.
• KEGG Pathway:
  Sphingolipid sig.ling pathway (hsa04071)
  Neuroactive ligand-receptor interaction (hsa04080)
• Reactome Pathway:
  Lysosphingolipid and LPA receptors (R-HSA-419408)
  G alpha (i) signalling events (R-HSA-418594)

Molecular Interaction Atlas (MIA) of This DOT

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the expression of Sphingosine 1-phosphate receptor 5 (S1PR5).	[1]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Sphingosine 1-phosphate receptor 5 (S1PR5).	[2]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Sphingosine 1-phosphate receptor 5 (S1PR5).	[3]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide decreases the expression of Sphingosine 1-phosphate receptor 5 (S1PR5).	[5]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of Sphingosine 1-phosphate receptor 5 (S1PR5).	[6]
Vorinostat	DMWMPD4	Approved	Vorinostat increases the expression of Sphingosine 1-phosphate receptor 5 (S1PR5).	[7]
Triclosan	DMZUR4N	Approved	Triclosan decreases the expression of Sphingosine 1-phosphate receptor 5 (S1PR5).	[8]
Decitabine	DMQL8XJ	Approved	Decitabine affects the expression of Sphingosine 1-phosphate receptor 5 (S1PR5).	[9]
Panobinostat	DM58WKG	Approved	Panobinostat increases the expression of Sphingosine 1-phosphate receptor 5 (S1PR5).	[10]
Cannabidiol	DM0659E	Approved	Cannabidiol decreases the expression of Sphingosine 1-phosphate receptor 5 (S1PR5).	[11]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Sphingosine 1-phosphate receptor 5 (S1PR5).	[10]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Sphingosine 1-phosphate receptor 5 (S1PR5).	[13]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of Sphingosine 1-phosphate receptor 5 (S1PR5).	[14]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic	DMTL2Y1	Approved	Arsenic increases the methylation of Sphingosine 1-phosphate receptor 5 (S1PR5).	[4]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Sphingosine 1-phosphate receptor 5 (S1PR5).	[12]

References

• [1] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [2] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [3] Genistein and bisphenol A exposure cause estrogen receptor 1 to bind thousands of sites in a cell type-specific manner. Genome Res. 2012 Nov;22(11):2153-62.
• [4] Epigenetic changes in individuals with arsenicosis. Chem Res Toxicol. 2011 Feb 18;24(2):165-7. doi: 10.1021/tx1004419. Epub 2011 Feb 4.
• [5] Identification of transcriptome signatures and biomarkers specific for potential developmental toxicants inhibiting human neural crest cell migration. Arch Toxicol. 2016 Jan;90(1):159-80.
• [6] Global gene expression analysis reveals differences in cellular responses to hydroxyl- and superoxide anion radical-induced oxidative stress in caco-2 cells. Toxicol Sci. 2010 Apr;114(2):193-203. doi: 10.1093/toxsci/kfp309. Epub 2009 Dec 31.
• [7] Definition of transcriptome-based indices for quantitative characterization of chemically disturbed stem cell development: introduction of the STOP-Toxukn and STOP-Toxukk tests. Arch Toxicol. 2017 Feb;91(2):839-864.
• [8] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [9] Acute hypersensitivity of pluripotent testicular cancer-derived embryonal carcinoma to low-dose 5-aza deoxycytidine is associated with global DNA Damage-associated p53 activation, anti-pluripotency and DNA demethylation. PLoS One. 2012;7(12):e53003. doi: 10.1371/journal.pone.0053003. Epub 2012 Dec 27.
• [10] A transcriptome-based classifier to identify developmental toxicants by stem cell testing: design, validation and optimization for histone deacetylase inhibitors. Arch Toxicol. 2015 Sep;89(9):1599-618.
• [11] Cannabidiol enhances cytotoxicity of anti-cancer drugs in human head and neck squamous cell carcinoma. Sci Rep. 2020 Nov 26;10(1):20622. doi: 10.1038/s41598-020-77674-y.
• [12] 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.
• [13] From transient transcriptome responses to disturbed neurodevelopment: role of histone acetylation and methylation as epigenetic switch between reversible and irreversible drug effects. Arch Toxicol. 2014 Jul;88(7):1451-68.
• [14] Gene expression changes in primary human nasal epithelial cells exposed to formaldehyde in vitro. Toxicol Lett. 2010 Oct 5;198(2):289-95.