Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTUNNTV5)

• DOT Name: Sphingosine 1-phosphate receptor 4 (S1PR4)
• Synonyms: S1P receptor 4; S1P4; Endothelial differentiation G-protein coupled receptor 6; Sphingosine 1-phosphate receptor Edg-6; S1P receptor Edg-6
• Gene Name: S1PR4
• UniProt ID: S1PR4_HUMAN
• PDB ID: 2DCO
• Pfam ID: PF00001
• Sequence:
  MNATGTPVAPESCQQLAAGGHSRLIVLHYNHSGRLAGRGGPEDGGLGALRGLSVAASCLV
  VLENLLVLAAITSHMRSRRWVYYCLVNITLSDLLTGAAYLANVLLSGARTFRLAPAQWFL
  REGLLFTALAASTFSLLFTAGERFATMVRPVAESGATKTSRVYGFIGLCWLLAALLGMLP
  LLGWNCLCAFDRCSSLLPLYSKRYILFCLVIFAGVLATIMGLYGAIFRLVQASGQKAPRP
  AARRKARRLLKTVLMILLAFLVCWGPLFGLLLADVFGSNLWAQEYLRGMDWILALAVLNS
  AVNPIIYSFRSREVCRAVLSFLCCGCLRLGMRGPGDCLARAVEAHSGASTTDSSLRPRDS
  FRGSRSLSFRMREPLSSISSVRSI
• 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. May be involved in cell migration processes that are specific for lymphocytes.
• Tissue Specificity: Specifically expressed in fetal and adult lymphoid and hematopoietic tissue as well as in lung. Considerable level of expression in adult and fetal spleen as well as adult peripheral leukocytes and lung. Lower expression in adult thymus, lymph node, bone marrow, and appendix as well as in fetal liver, thymus, and lung.
• KEGG Pathway:
  FoxO sig.ling pathway (hsa04068)
  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

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the methylation of Sphingosine 1-phosphate receptor 4 (S1PR4).	[1]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Sphingosine 1-phosphate receptor 4 (S1PR4).	[2]
Arsenic	DMTL2Y1	Approved	Arsenic affects the expression of Sphingosine 1-phosphate receptor 4 (S1PR4).	[3]
Marinol	DM70IK5	Approved	Marinol increases the expression of Sphingosine 1-phosphate receptor 4 (S1PR4).	[4]
GSK2110183	DMZHB37	Phase 2	GSK2110183 increases the expression of Sphingosine 1-phosphate receptor 4 (S1PR4).	[5]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of Sphingosine 1-phosphate receptor 4 (S1PR4).	[6]

References

• [1] Integrative omics data analyses of repeated dose toxicity of valproic acid in vitro reveal new mechanisms of steatosis induction. Toxicology. 2018 Jan 15;393:160-170.
• [2] Blood transcript immune signatures distinguish a subset of people with elevated serum ALT from others given acetaminophen. Clin Pharmacol Ther. 2016 Apr;99(4):432-41.
• [3] Drinking-water arsenic exposure modulates gene expression in human lymphocytes from a U.S. population. Environ Health Perspect. 2008 Apr;116(4):524-31. doi: 10.1289/ehp.10861.
• [4] Single-cell Transcriptome Mapping Identifies Common and Cell-type Specific Genes Affected by Acute Delta9-tetrahydrocannabinol in Humans. Sci Rep. 2020 Feb 26;10(1):3450. doi: 10.1038/s41598-020-59827-1.
• [5] Novel ATP-competitive Akt inhibitor afuresertib suppresses the proliferation of malignant pleural mesothelioma cells. Cancer Med. 2017 Nov;6(11):2646-2659. doi: 10.1002/cam4.1179. Epub 2017 Sep 27.
• [6] Inter- and intra-laboratory study to determine the reproducibility of toxicogenomics datasets. Toxicology. 2011 Nov 28;290(1):50-8.