Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT4JJAQG)

• DOT Name: Adhesion G-protein coupled receptor G5 (ADGRG5)
• Synonyms: G-protein coupled receptor 114; G-protein coupled receptor PGR27
• Gene Name: ADGRG5
• UniProt ID: AGRG5_HUMAN
• PDB ID: 7EQ1
• Pfam ID: PF00002 ; PF01825
• Sequence:
  MDHCGALFLCLCLLTLQNATTETWEELLSYMENMQVSRGRSSVFSSRQLHQLEQMLLNTS
  FPGYNLTLQTPTIQSLAFKLSCDFSGLSLTSATLKRVPQAGGQHARGQHAMQFPAELTRD
  ACKTRPRELRLICIYFSNTHFFKDENNSSLLNNYVLGAQLSHGHVNNLRDPVNISFWHNQ
  SLEGYTLTCVFWKEGARKQPWGGWSPEGCRTEQPSHSQVLCRCNHLTYFAVLMQLSPALV
  PAELLAPLTYISLVGCSISIVASLITVLLHFHFRKQSDSLTRIHMNLHASVLLLNIAFLL
  SPAFAMSPVPGSACTALAAALHYALLSCLTWMAIEGFNLYLLLGRVYNIYIRRYVFKLGV
  LGWGAPALLVLLSLSVKSSVYGPCTIPVFDSWENGTGFQNMSICWVRSPVVHSVLVMGYG
  GLTSLFNLVVLAWALWTLRRLRERADAPSVRACHDTVTVLGLTVLLGTTWALAFFSFGVF
  LLPQLFLFTILNSLYGFFLFLWFCSQRCRSEAEAKAQIEAFSSSQTTQ
• Function: Adhesion G protein-coupled receptor (GPCR). Transduces intracellular signals through coupling to guanine nucleotide-binding protein G(s) subunit alpha and activation of adenylate cyclase pathway. Isoform 1, but not isoform 2, is constitutively active, as evidenced by elevated basal cAMP levels, and responds to mechanical activation (shaking).
• Tissue Specificity: Expressed in immune cells. Primarily found in granulocytes. Found in eosinophils.

Molecular Interaction Atlas (MIA) of This DOT

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the expression of Adhesion G-protein coupled receptor G5 (ADGRG5).	[1]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Adhesion G-protein coupled receptor G5 (ADGRG5).	[2]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide increases the expression of Adhesion G-protein coupled receptor G5 (ADGRG5).	[3]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Adhesion G-protein coupled receptor G5 (ADGRG5).	[5]

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 increases the methylation of Adhesion G-protein coupled receptor G5 (ADGRG5).	[4]

References

• [1] Effects of lithium and valproic acid on gene expression and phenotypic markers in an NT2 neurosphere model of neural development. PLoS One. 2013;8(3):e58822.
• [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] Oxidative stress modulates theophylline effects on steroid responsiveness. Biochem Biophys Res Commun. 2008 Dec 19;377(3):797-802.
• [4] 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.
• [5] CCAT1 is an enhancer-templated RNA that predicts BET sensitivity in colorectal cancer. J Clin Invest. 2016 Feb;126(2):639-52.