Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTB3XFA1)

• DOT Name: Adhesion G protein-coupled receptor G3 (ADGRG3)
• Synonyms: G-protein coupled receptor 97; G-protein coupled receptor PGR26
• Gene Name: ADGRG3
• Related Disease:
  Autoimmune disease
  Nervous system inflammation
• UniProt ID: AGRG3_HUMAN
• PDB ID: 7D76; 7D77; 7QU8
• Pfam ID: PF00002 ; PF01825
• Sequence:
  MATPRGLGALLLLLLLPTSGQEKPTEGPRNTCLGSNNMYDIFNLNDKALCFTKCRQSGSD
  SCNVENLQRYWLNYEAHLMKEGLTQKVNTPFLKALVQNLSTNTAEDFYFSLEPSQVPRQV
  MKDEDKPPDRVRLPKSLFRSLPGNRSVVRLAVTILDIGPGTLFKGPRLGLGDGSGVLNNR
  LVGLSVGQMHVTKLAEPLEIVFSHQRPPPNMTLTCVFWDVTKGTTGDWSSEGCSTEVRPE
  GTVCCCDHLTFFALLLRPTLDQSTVHILTRISQAGCGVSMIFLAFTIILYAFLRLSRERF
  KSEDAPKIHVALGGSLFLLNLAFLVNVGSGSKGSDAACWARGAVFHYFLLCAFTWMGLEA
  FHLYLLAVRVFNTYFGHYFLKLSLVGWGLPALMVIGTGSANSYGLYTIRDRENRTSLELC
  WFREGTTMYALYITVHGYFLITFLFGMVVLALVVWKIFTLSRATAVKERGKNRKKVLTLL
  GLSSLVGVTWGLAIFTPLGLSTVYIFALFNSLQGVFICCWFTILYLPSQSTTVSSSTARL
  DQAHSASQE
• Function: Orphan receptor that regulates migration of lymphatic endothelial cells in vitro via the small GTPases RhoA and CDC42. Regulates B-cell development. Seems to signal through G-alpha(q)-proteins.
• Tissue Specificity: Expressed in cultured primary dermal lymphatic endothelial cells.
• Reactome Pathway: Neutrophil degranulation (R-HSA-6798695)

Molecular Interaction Atlas (MIA) of This DOT

2 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Autoimmune disease	DISORMTM	Limited	Biomarker	[1]
Nervous system inflammation	DISB3X5A	Limited	Biomarker	[1]

6 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 Adhesion G protein-coupled receptor G3 (ADGRG3).	[2]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Adhesion G protein-coupled receptor G3 (ADGRG3).	[3]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Adhesion G protein-coupled receptor G3 (ADGRG3).	[4]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Adhesion G protein-coupled receptor G3 (ADGRG3).	[5]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide increases the expression of Adhesion G protein-coupled receptor G3 (ADGRG3).	[7]
Sulforaphane	DMQY3L0	Investigative	Sulforaphane increases the expression of Adhesion G protein-coupled receptor G3 (ADGRG3).	[8]

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 Adhesion G protein-coupled receptor G3 (ADGRG3).	[6]

References

• [1] Gpr97/Adgrg3 ameliorates experimental autoimmune encephalomyelitis by regulating cytokine expression.Acta Biochim Biophys Sin (Shanghai). 2018 Jul 1;50(7):666-675. doi: 10.1093/abbs/gmy060.
• [2] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [3] 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.
• [4] 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.
• [5] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [6] 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.
• [7] Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
• [8] 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.