Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT8J0TF8)

• DOT Name: C3a anaphylatoxin chemotactic receptor (C3AR1)
• Synonyms: C3AR; C3a-R
• Gene Name: C3AR1
• UniProt ID: C3AR_HUMAN
• PDB ID: 8HK2; 8HK3; 8I95; 8I97; 8I9A; 8I9L; 8I9S; 8IA8; 8J6D
• Pfam ID: PF00001
• Sequence:
  MASFSAETNSTDLLSQPWNEPPVILSMVILSLTFLLGLPGNGLVLWVAGLKMQRTVNTIW
  FLHLTLADLLCCLSLPFSLAHLALQGQWPYGRFLCKLIPSIIVLNMFASVFLLTAISLDR
  CLVVFKPIWCQNHRNVGMACSICGCIWVVAFVMCIPVFVYREIFTTDNHNRCGYKFGLSS
  SLDYPDFYGDPLENRSLENIVQPPGEMNDRLDPSSFQTNDHPWTVPTVFQPQTFQRPSAD
  SLPRGSARLTSQNLYSNVFKPADVVSPKIPSGFPIEDHETSPLDNSDAFLSTHLKLFPSA
  SSNSFYESELPQGFQDYYNLGQFTDDDQVPTPLVAITITRLVVGFLLPSVIMIACYSFIV
  FRMQRGRFAKSQSKTFRVAVVVVAVFLVCWTPYHIFGVLSLLTDPETPLGKTLMSWDHVC
  IALASANSCFNPFLYALLGKDFRKKARQSIQGILEAAFSEELTRSTHCPSNNVISERNST
  TV
• Function: Receptor for the chemotactic and inflammatory peptide anaphylatoxin C3a. This receptor stimulates chemotaxis, granule enzyme release and superoxide anion production.
• Tissue Specificity: Widely expressed in several differentiated hematopoietic cell lines, in the lung, spleen, ovary, placenta, small intestine, throughout the brain, heart, and endothelial cells. Mostly expressed in lymphoid tissues.
• KEGG Pathway:
  Neuroactive ligand-receptor interaction (hsa04080)
  Complement and coagulation cascades (hsa04610)
  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)
  Purinergic signaling in leishmaniasis infection (R-HSA-9660826)
  Regulation of Complement cascade (R-HSA-977606)
  Peptide ligand-binding receptors (R-HSA-375276)

Molecular Interaction Atlas (MIA) of This DOT

10 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 C3a anaphylatoxin chemotactic receptor (C3AR1).	[1]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of C3a anaphylatoxin chemotactic receptor (C3AR1).	[2]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of C3a anaphylatoxin chemotactic receptor (C3AR1).	[3]
Calcitriol	DM8ZVJ7	Approved	Calcitriol decreases the expression of C3a anaphylatoxin chemotactic receptor (C3AR1).	[4]
Folic acid	DMEMBJC	Approved	Folic acid decreases the expression of C3a anaphylatoxin chemotactic receptor (C3AR1).	[5]
Cytarabine	DMZD5QR	Approved	Cytarabine increases the expression of C3a anaphylatoxin chemotactic receptor (C3AR1).	[6]
Nicotine	DMWX5CO	Approved	Nicotine increases the expression of C3a anaphylatoxin chemotactic receptor (C3AR1).	[7]
Azacitidine	DMTA5OE	Approved	Azacitidine increases the expression of C3a anaphylatoxin chemotactic receptor (C3AR1).	[6]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of C3a anaphylatoxin chemotactic receptor (C3AR1).	[9]
Sulforaphane	DMQY3L0	Investigative	Sulforaphane increases the expression of C3a anaphylatoxin chemotactic receptor (C3AR1).	[10]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of C3a anaphylatoxin chemotactic receptor (C3AR1).	[8]

References

• [1] 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.
• [2] Gene expression analysis of precision-cut human liver slices indicates stable expression of ADME-Tox related genes. Toxicol Appl Pharmacol. 2011 May 15;253(1):57-69.
• [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] Identification of vitamin D3 target genes in human breast cancer tissue. J Steroid Biochem Mol Biol. 2016 Nov;164:90-97.
• [5] Folic acid supplementation dysregulates gene expression in lymphoblastoid cells--implications in nutrition. Biochem Biophys Res Commun. 2011 Sep 9;412(4):688-92. doi: 10.1016/j.bbrc.2011.08.027. Epub 2011 Aug 16.
• [6] The DNA methyltransferase inhibitors azacitidine, decitabine and zebularine exert differential effects on cancer gene expression in acute myeloid leukemia cells. Leukemia. 2009 Jun;23(6):1019-28.
• [7] Characterizing the genetic basis for nicotine induced cancer development: a transcriptome sequencing study. PLoS One. 2013 Jun 18;8(6):e67252.
• [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] 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.
• [10] 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.