Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT982ECU)

• DOT Name: Proteinase-activated receptor 3 (F2RL2)
• Synonyms: PAR-3; Coagulation factor II receptor-like 2; Thrombin receptor-like 2
• Gene Name: F2RL2
• UniProt ID: PAR3_HUMAN
• Pfam ID: PF00001
• Sequence:
  MKALIFAAAGLLLLLPTFCQSGMENDTNNLAKPTLPIKTFRGAPPNSFEEFPFSALEGWT
  GATITVKIKCPEESASHLHVKNATMGYLTSSLSTKLIPAIYLLVFVVGVPANAVTLWMLF
  FRTRSICTTVFYTNLAIADFLFCVTLPFKIAYHLNGNNWVFGEVLCRATTVIFYGNMYCS
  ILLLACISINRYLAIVHPFTYRGLPKHTYALVTCGLVWATVFLYMLPFFILKQEYYLVQP
  DITTCHDVHNTCESSSPFQLYYFISLAFFGFLIPFVLIIYCYAAIIRTLNAYDHRWLWYV
  KASLLILVIFTICFAPSNIILIIHHANYYYNNTDGLYFIYLIALCLGSLNSCLDPFLYFL
  MSKTRNHSTAYLTK
• Function: Receptor for activated thrombin coupled to G proteins that stimulate phosphoinositide hydrolysis.
• Tissue Specificity: Highest expression in the megakaryocytes of the bone marrow, lower in mature megakaryocytes, in platelets and in a variety of other tissues such as heart and gut.
• KEGG Pathway:
  Neuroactive ligand-receptor interaction (hsa04080)
  Complement and coagulation cascades (hsa04610)
• Reactome Pathway:
  G alpha (q) signalling events (R-HSA-416476)
  Thrombin signalling through proteinase activated receptors (PARs) (R-HSA-456926)
  Peptide ligand-binding receptors (R-HSA-375276)

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 decreases the methylation of Proteinase-activated receptor 3 (F2RL2).	[1]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Proteinase-activated receptor 3 (F2RL2).	[2]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Proteinase-activated receptor 3 (F2RL2).	[3]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Proteinase-activated receptor 3 (F2RL2).	[4]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Proteinase-activated receptor 3 (F2RL2).	[5]
Calcitriol	DM8ZVJ7	Approved	Calcitriol decreases the expression of Proteinase-activated receptor 3 (F2RL2).	[6]
Vorinostat	DMWMPD4	Approved	Vorinostat decreases the expression of Proteinase-activated receptor 3 (F2RL2).	[7]
Triclosan	DMZUR4N	Approved	Triclosan decreases the expression of Proteinase-activated receptor 3 (F2RL2).	[8]
Progesterone	DMUY35B	Approved	Progesterone decreases the expression of Proteinase-activated receptor 3 (F2RL2).	[9]
Panobinostat	DM58WKG	Approved	Panobinostat decreases the expression of Proteinase-activated receptor 3 (F2RL2).	[7]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 decreases the expression of Proteinase-activated receptor 3 (F2RL2).	[7]
PEITC	DMOMN31	Phase 2	PEITC increases the expression of Proteinase-activated receptor 3 (F2RL2).	[10]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of Proteinase-activated receptor 3 (F2RL2).	[11]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Proteinase-activated receptor 3 (F2RL2).	[12]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Proteinase-activated receptor 3 (F2RL2).	[13]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of Proteinase-activated receptor 3 (F2RL2).	[14]
QUERCITRIN	DM1DH96	Investigative	QUERCITRIN decreases the expression of Proteinase-activated receptor 3 (F2RL2).	[15]
Lead acetate	DML0GZ2	Investigative	Lead acetate increases the expression of Proteinase-activated receptor 3 (F2RL2).	[16]

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] Comparison of HepG2 and HepaRG by whole-genome gene expression analysis for the purpose of chemical hazard identification. Toxicol Sci. 2010 May;115(1):66-79.
• [3] Development of a neural teratogenicity test based on human embryonic stem cells: response to retinoic acid exposure. Toxicol Sci. 2011 Dec;124(2):370-7.
• [4] Bringing in vitro analysis closer to in vivo: studying doxorubicin toxicity and associated mechanisms in 3D human microtissues with PBPK-based dose modelling. Toxicol Lett. 2018 Sep 15;294:184-192.
• [5] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [6] Identification of vitamin D3 target genes in human breast cancer tissue. J Steroid Biochem Mol Biol. 2016 Nov;164:90-97.
• [7] 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.
• [8] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [9] Unique transcriptome, pathways, and networks in the human endometrial fibroblast response to progesterone in endometriosis. Biol Reprod. 2011 Apr;84(4):801-15.
• [10] Phenethyl isothiocyanate alters the gene expression and the levels of protein associated with cell cycle regulation in human glioblastoma GBM 8401 cells. Environ Toxicol. 2017 Jan;32(1):176-187.
• [11] Transcriptional signature of human macrophages exposed to the environmental contaminant benzo(a)pyrene. Toxicol Sci. 2010 Apr;114(2):247-59.
• [12] Inhibition of BRD4 attenuates tumor cell self-renewal and suppresses stem cell signaling in MYC driven medulloblastoma. Oncotarget. 2014 May 15;5(9):2355-71.
• [13] Bisphenol A induces DSB-ATM-p53 signaling leading to cell cycle arrest, senescence, autophagy, stress response, and estrogen release in human fetal lung fibroblasts. Arch Toxicol. 2018 Apr;92(4):1453-1469.
• [14] 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.
• [15] Molecular mechanisms of quercitrin-induced apoptosis in non-small cell lung cancer. Arch Med Res. 2014 Aug;45(6):445-54.
• [16] In vitro effects of lead on gene expression in neural stem cells and associations between up-regulated genes and cognitive scores in children. Environ Health Perspect. 2017 Apr;125(4):721-729.