Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT2133DF)

• DOT Name: Platelet-activating factor receptor (PTAFR)
• Synonyms: PAF-R; PAFr
• Gene Name: PTAFR
• UniProt ID: PTAFR_HUMAN
• Pfam ID: PF00001
• Sequence:
  MEPHDSSHMDSEFRYTLFPIVYSIIFVLGVIANGYVLWVFARLYPCKKFNEIKIFMVNLT
  MADMLFLITLPLWIVYYQNQGNWILPKFLCNVAGCLFFINTYCSVAFLGVITYNRFQAVT
  RPIKTAQANTRKRGISLSLVIWVAIVGAASYFLILDSTNTVPDSAGSGNVTRCFEHYEKG
  SVPVLIIHIFIVFSFFLVFLIILFCNLVIIRTLLMQPVQQQRNAEVKRRALWMVCTVLAV
  FIICFVPHHVVQLPWTLAELGFQDSKFHQAINDAHQVTLCLLSTNCVLDPVIYCFLTKKF
  RKHLTEKFYSMRSSRKCSRATTDTVTEVVVPFNQIPGNSLKN
• Function: Receptor for platelet activating factor, a chemotactic phospholipid mediator that possesses potent inflammatory, smooth-muscle contractile and hypotensive activity. Seems to mediate its action via a G protein that activates a phosphatidylinositol-calcium second messenger system.
• Tissue Specificity: Expressed in the placenta, lung, left and right heart ventricles, heart atrium, leukocytes and differentiated HL-60 granulocytes.
• KEGG Pathway:
  Calcium sig.ling pathway (hsa04020)
  Neuroactive ligand-receptor interaction (hsa04080)
  Staphylococcus aureus infection (hsa05150)
• Reactome Pathway:
  G alpha (q) signalling events (R-HSA-416476)
  Interleukin-10 signaling (R-HSA-6783783)
  Neutrophil degranulation (R-HSA-6798695)
  Interferon gamma signaling (R-HSA-877300)
  Class A/1 (Rhodopsin-like receptors) (R-HSA-373076)

Molecular Interaction Atlas (MIA) of This DOT

This DOT Affected the Drug Response of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Alprazolam	DMC7XDN	Approved	Platelet-activating factor receptor (PTAFR) increases the Anterograde amnesia ADR of Alprazolam.	[11]

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 Platelet-activating factor receptor (PTAFR).	[1]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Platelet-activating factor receptor (PTAFR).	[2]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Platelet-activating factor receptor (PTAFR).	[3]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Platelet-activating factor receptor (PTAFR).	[4]
Estradiol	DMUNTE3	Approved	Estradiol affects the expression of Platelet-activating factor receptor (PTAFR).	[5]
Marinol	DM70IK5	Approved	Marinol increases the expression of Platelet-activating factor receptor (PTAFR).	[6]
Demecolcine	DMCZQGK	Approved	Demecolcine increases the expression of Platelet-activating factor receptor (PTAFR).	[7]
Nicotine	DMWX5CO	Approved	Nicotine decreases the expression of Platelet-activating factor receptor (PTAFR).	[8]
Salbutamol	DMN9CWF	Approved	Salbutamol increases the expression of Platelet-activating factor receptor (PTAFR).	[9]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Platelet-activating factor receptor (PTAFR).	[8]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Platelet-activating factor receptor (PTAFR).	[10]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A affects the expression of Platelet-activating factor receptor (PTAFR).	[5]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of Platelet-activating factor receptor (PTAFR).	[7]

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] Transcriptional and Metabolic Dissection of ATRA-Induced Granulocytic Differentiation in NB4 Acute Promyelocytic Leukemia Cells. Cells. 2020 Nov 5;9(11):2423. doi: 10.3390/cells9112423.
• [3] Predictive toxicology using systemic biology and liver microfluidic "on chip" approaches: application to acetaminophen injury. Toxicol Appl Pharmacol. 2012 Mar 15;259(3):270-80.
• [4] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [5] Gene alterations of ovarian cancer cells expressing estrogen receptors by estrogen and bisphenol a using microarray analysis. Lab Anim Res. 2011 Jun;27(2):99-107. doi: 10.5625/lar.2011.27.2.99. Epub 2011 Jun 22.
• [6] 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.
• [7] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
• [8] Effects of tobacco compounds on gene expression in fetal lung fibroblasts. Environ Toxicol. 2008 Aug;23(4):423-34.
• [9] Mechanisms by which S-albuterol induces human bronchial smooth muscle cell proliferation. Int Arch Allergy Immunol. 2008;146(4):321-33. doi: 10.1159/000121466. Epub 2008 Mar 21.
• [10] Targeting MYC dependence in cancer by inhibiting BET bromodomains. Proc Natl Acad Sci U S A. 2011 Oct 4;108(40):16669-74. doi: 10.1073/pnas.1108190108. Epub 2011 Sep 26.
• [11] ADReCS-Target: target profiles for aiding drug safety research and application. Nucleic Acids Res. 2018 Jan 4;46(D1):D911-D917. doi: 10.1093/nar/gkx899.