Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTEZ2THZ)

• DOT Name: N-formyl peptide receptor 2 (FPR2)
• Synonyms: FMLP-related receptor I; FMLP-R-I; Formyl peptide receptor-like 1; HM63; Lipoxin A4 receptor; LXA4 receptor; RFP
• Gene Name: FPR2
• UniProt ID: FPR2_HUMAN
• PDB ID: 6LW5; 6OMM; 7T6S; 7T6U; 7T6V; 7WVV; 7WVW; 7WVX; 7WVY
• Pfam ID: PF00001
• Sequence:
  METNFSTPLNEYEEVSYESAGYTVLRILPLVVLGVTFVLGVLGNGLVIWVAGFRMTRTVT
  TICYLNLALADFSFTATLPFLIVSMAMGEKWPFGWFLCKLIHIVVDINLFGSVFLIGFIA
  LDRCICVLHPVWAQNHRTVSLAMKVIVGPWILALVLTLPVFLFLTTVTIPNGDTYCTFNF
  ASWGGTPEERLKVAITMLTARGIIRFVIGFSLPMSIVAICYGLIAAKIHKKGMIKSSRPL
  RVLTAVVASFFICWFPFQLVALLGTVWLKEMLFYGKYKIIDILVNPTSSLAFFNSCLNPM
  LYVFVGQDFRERLIHSLPTSLERALSEDSAPTNDTAANSASPPAETELQAM
• Function: Low affinity receptor for N-formyl-methionyl peptides, which are powerful neutrophil chemotactic factors. Binding of FMLP to the receptor causes activation of neutrophils. This response is mediated via a G-protein that activates a phosphatidylinositol-calcium second messenger system. The activation of LXA4R could result in an anti-inflammatory outcome counteracting the actions of pro-inflammatory signals such as LTB4 (leukotriene B4). Receptor for the chemokine-like protein FAM19A5, mediating FAM19A5-stimulated macrophage chemotaxis and the inhibitory effect on TNFSF11/RANKL-induced osteoclast differentiation. Acts as a receptor for humanin.
• Tissue Specificity: Detected in lung, bone marrow, neutrophils, spleen and testis.
• KEGG Pathway:
  Neuroactive ligand-receptor interaction (hsa04080)
  Neutrophil extracellular trap formation (hsa04613)
  Staphylococcus aureus infection (hsa05150)
• Reactome Pathway:
  G alpha (i) signalling events (R-HSA-418594)
  Formyl peptide receptors bind formyl peptides and many other ligands (R-HSA-444473)
  Neutrophil degranulation (R-HSA-6798695)
  G alpha (q) signalling events (R-HSA-416476)

Molecular Interaction Atlas (MIA) of This DOT

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the methylation of N-formyl peptide receptor 2 (FPR2).	[1]
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of N-formyl peptide receptor 2 (FPR2).	[4]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of N-formyl peptide receptor 2 (FPR2).	[8]

6 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 N-formyl peptide receptor 2 (FPR2).	[2]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of N-formyl peptide receptor 2 (FPR2).	[3]
Quercetin	DM3NC4M	Approved	Quercetin increases the expression of N-formyl peptide receptor 2 (FPR2).	[5]
Methotrexate	DM2TEOL	Approved	Methotrexate decreases the expression of N-formyl peptide receptor 2 (FPR2).	[6]
Aspirin	DM672AH	Approved	Aspirin increases the expression of N-formyl peptide receptor 2 (FPR2).	[7]
Sulforaphane	DMQY3L0	Investigative	Sulforaphane increases the expression of N-formyl peptide receptor 2 (FPR2).	[9]

References

• [1] Integrative "-Omics" analysis in primary human hepatocytes unravels persistent mechanisms of cyclosporine A-induced cholestasis. Chem Res Toxicol. 2016 Dec 19;29(12):2164-2174.
• [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] Low doses of cisplatin induce gene alterations, cell cycle arrest, and apoptosis in human promyelocytic leukemia cells. Biomark Insights. 2016 Aug 24;11:113-21.
• [4] Prenatal arsenic exposure and the epigenome: identifying sites of 5-methylcytosine alterations that predict functional changes in gene expression in newborn cord blood and subsequent birth outcomes. Toxicol Sci. 2015 Jan;143(1):97-106. doi: 10.1093/toxsci/kfu210. Epub 2014 Oct 10.
• [5] Integrated assessment by multiple gene expression analysis of quercetin bioactivity on anticancer-related mechanisms in colon cancer cells in vitro. Eur J Nutr. 2005 Mar;44(3):143-56. doi: 10.1007/s00394-004-0503-1. Epub 2004 Apr 30.
• [6] The contribution of methotrexate exposure and host factors on transcriptional variance in human liver. Toxicol Sci. 2007 Jun;97(2):582-94.
• [7] Effects of low-dose aspirin on acute inflammatory responses in humans. J Immunol. 2009 Aug 1;183(3):2089-96. doi: 10.4049/jimmunol.0900477. Epub 2009 Jul 13.
• [8] 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.
• [9] Sulforaphane-induced apoptosis in human leukemia HL-60 cells through extrinsic and intrinsic signal pathways and altering associated genes expression assayed by cDNA microarray. Environ Toxicol. 2017 Jan;32(1):311-328.