Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT58QDI9)

• DOT Name: C5a anaphylatoxin chemotactic receptor 1 (C5AR1)
• Synonyms: C5a anaphylatoxin chemotactic receptor; C5a-R; C5aR; CD antigen CD88
• Gene Name: C5AR1
• UniProt ID: C5AR1_HUMAN
• PDB ID: 2K3U; 5O9H; 6C1Q; 6C1R; 7Y64; 7Y65; 7Y66; 7Y67; 8GO8; 8GOO; 8HK5; 8I0N; 8I0Z; 8IA2; 8JZZ
• Pfam ID: PF00001
• Sequence:
  MDSFNYTTPDYGHYDDKDTLDLNTPVDKTSNTLRVPDILALVIFAVVFLVGVLGNALVVW
  VTAFEAKRTINAIWFLNLAVADFLSCLALPILFTSIVQHHHWPFGGAACSILPSLILLNM
  YASILLLATISADRFLLVFKPIWCQNFRGAGLAWIACAVAWGLALLLTIPSFLYRVVREE
  YFPPKVLCGVDYSHDKRRERAVAIVRLVLGFLWPLLTLTICYTFILLRTWSRRATRSTKT
  LKVVVAVVASFFIFWLPYQVTGIMMSFLEPSSPTFLLLKKLDSLCVSFAYINCCINPIIY
  VVAGQGFQGRLRKSLPSLLRNVLTEESVVRESKSFTRSTVDTMAQKTQAV
• Function: Receptor for the chemotactic and inflammatory peptide anaphylatoxin C5a. The ligand interacts with at least two sites on the receptor: a high-affinity site on the extracellular N-terminus, and a second site in the transmembrane region which activates downstream signaling events. Receptor activation stimulates chemotaxis, granule enzyme release, intracellular calcium release and superoxide anion production.
• KEGG Pathway:
  Neuroactive ligand-receptor interaction (hsa04080)
  Complement and coagulation cascades (hsa04610)
  Neutrophil extracellular trap formation (hsa04613)
  Alcoholic liver disease (hsa04936)
  Staphylococcus aureus infection (hsa05150)
  Coro.virus disease - COVID-19 (hsa05171)
• Reactome Pathway:
  G alpha (i) signalling events (R-HSA-418594)
  Neutrophil degranulation (R-HSA-6798695)
  Regulation of Complement cascade (R-HSA-977606)
  Peptide ligand-binding receptors (R-HSA-375276)

Molecular Interaction Atlas (MIA) of This DOT

11 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 C5a anaphylatoxin chemotactic receptor 1 (C5AR1).	[1]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of C5a anaphylatoxin chemotactic receptor 1 (C5AR1).	[2]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of C5a anaphylatoxin chemotactic receptor 1 (C5AR1).	[3]
Quercetin	DM3NC4M	Approved	Quercetin increases the expression of C5a anaphylatoxin chemotactic receptor 1 (C5AR1).	[4]
Methotrexate	DM2TEOL	Approved	Methotrexate decreases the expression of C5a anaphylatoxin chemotactic receptor 1 (C5AR1).	[5]
Nicotine	DMWX5CO	Approved	Nicotine decreases the expression of C5a anaphylatoxin chemotactic receptor 1 (C5AR1).	[6]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of C5a anaphylatoxin chemotactic receptor 1 (C5AR1).	[7]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the mutagenesis of C5a anaphylatoxin chemotactic receptor 1 (C5AR1).	[8]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide increases the expression of C5a anaphylatoxin chemotactic receptor 1 (C5AR1).	[9]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A affects the expression of C5a anaphylatoxin chemotactic receptor 1 (C5AR1).	[10]
Resorcinol	DMM37C0	Investigative	Resorcinol decreases the expression of C5a anaphylatoxin chemotactic receptor 1 (C5AR1).	[11]

References

• [1] 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.
• [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] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [4] Comparison of phenotypic and transcriptomic effects of false-positive genotoxins, true genotoxins and non-genotoxins using HepG2 cells. Mutagenesis. 2011 Sep;26(5):593-604.
• [5] The contribution of methotrexate exposure and host factors on transcriptional variance in human liver. Toxicol Sci. 2007 Jun;97(2):582-94.
• [6] Effects of tobacco compounds on gene expression in fetal lung fibroblasts. Environ Toxicol. 2008 Aug;23(4):423-34.
• [7] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [8] Exome-wide mutation profile in benzo[a]pyrene-derived post-stasis and immortal human mammary epithelial cells. Mutat Res Genet Toxicol Environ Mutagen. 2014 Dec;775-776:48-54. doi: 10.1016/j.mrgentox.2014.10.011. Epub 2014 Nov 4.
• [9] Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
• [10] Comprehensive analysis of transcriptomic changes induced by low and high doses of bisphenol A in HepG2 spheroids in vitro and rat liver in vivo. Environ Res. 2019 Jun;173:124-134. doi: 10.1016/j.envres.2019.03.035. Epub 2019 Mar 18.
• [11] A transcriptomics-based in vitro assay for predicting chemical genotoxicity in vivo. Carcinogenesis. 2012 Jul;33(7):1421-9.