Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT0PVQCW)

• DOT Name: Adhesion G-protein coupled receptor D1 (ADGRD1)
• Synonyms: G-protein coupled receptor 133; G-protein coupled receptor PGR25
• Gene Name: ADGRD1
• Related Disease: Amyotrophic lateral sclerosis type 1
• UniProt ID: AGRD1_HUMAN
• PDB ID: 7EPT; 7WU2
• Pfam ID: PF00002 ; PF01825 ; PF13385
• Sequence:
  MEKLLRLCCWYSWLLLFYYNFQVRGVYSRSQDHPGFQVLASASHYWPLENVDGIHELQDT
  TGDIVEGKVNKGIYLKEEKGVTLLYYGRYNSSCISKPEQCGPEGVTFSFFWKTQGEQSRP
  IPSAYGGQVISNGFKVCSSGGRGSVELYTRDNSMTWEASFSPPGPYWTHVLFTWKSKEGL
  KVYVNGTLSTSDPSGKVSRDYGESNVNLVIGSEQDQAKCYENGAFDEFIIWERALTPDEI
  AMYFTAAIGKHALLSSTLPSLFMTSTASPVMPTDAYHPIITNLTEERKTFQSPGVILSYL
  QNVSLSLPSKSLSEQTALNLTKTFLKAVGEILLLPGWIALSEDSAVVLSLIDTIDTVMGH
  VSSNLHGSTPQVTVEGSSAMAEFSVAKILPKTVNSSHYRFPAHGQSFIQIPHEAFHRHAW
  STVVGLLYHSMHYYLNNIWPAHTKIAEAMHHQDCLLFATSHLISLEVSPPPTLSQNLSGS
  PLITVHLKHRLTRKQHSEATNSSNRVFVYCAFLDFSSGEGVWSNHGCALTRGNLTYSVCR
  CTHLTNFAILMQVVPLELARGHQVALSSISYVGCSLSVLCLVATLVTFAVLSSVSTIRNQ
  RYHIHANLSFAVLVAQVLLLISFRLEPGTTPCQVMAVLLHYFFLSAFAWMLVEGLHLYSM
  VIKVFGSEDSKHRYYYGMGWGFPLLICIISLSFAMDSYGTSNNCWLSLASGAIWAFVAPA
  LFVIVVNIGILIAVTRVISQISADNYKIHGDPSAFKLTAKAVAVLLPILGTSWVFGVLAV
  NGCAVVFQYMFATLNSLQGLFIFLFHCLLNSEVRAAFKHKTKVWSLTSSSARTSNAKPFH
  SDLMNGTRPGMASTKLSPWDKSSHSAHRVDLSAV
• Function: Orphan receptor. Signals via G(s)-alpha family of G-proteins. Has protumorigenic function especially in glioblastoma.
• Tissue Specificity: Up-regulated in CD133(+) cell population of glioblastoma.

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Amyotrophic lateral sclerosis type 1	DIS5A2M0	Limited	Genetic Variation	[1]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the methylation of Adhesion G-protein coupled receptor D1 (ADGRD1).	[2]
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of Adhesion G-protein coupled receptor D1 (ADGRD1).	[6]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Adhesion G-protein coupled receptor D1 (ADGRD1).	[12]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Adhesion G-protein coupled receptor D1 (ADGRD1).	[13]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Adhesion G-protein coupled receptor D1 (ADGRD1).	[3]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Adhesion G-protein coupled receptor D1 (ADGRD1).	[4]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Adhesion G-protein coupled receptor D1 (ADGRD1).	[5]
Testosterone	DM7HUNW	Approved	Testosterone decreases the expression of Adhesion G-protein coupled receptor D1 (ADGRD1).	[7]
Triclosan	DMZUR4N	Approved	Triclosan decreases the expression of Adhesion G-protein coupled receptor D1 (ADGRD1).	[8]
Folic acid	DMEMBJC	Approved	Folic acid decreases the expression of Adhesion G-protein coupled receptor D1 (ADGRD1).	[9]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Adhesion G-protein coupled receptor D1 (ADGRD1).	[10]
Amiodarone	DMUTEX3	Phase 2/3 Trial	Amiodarone increases the expression of Adhesion G-protein coupled receptor D1 (ADGRD1).	[11]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Adhesion G-protein coupled receptor D1 (ADGRD1).	[14]
Sulforaphane	DMQY3L0	Investigative	Sulforaphane decreases the expression of Adhesion G-protein coupled receptor D1 (ADGRD1).	[15]

References

• [1] Genome-wide association study combining pathway analysis for typical sporadic amyotrophic lateral sclerosis in Chinese Han populations.Neurobiol Aging. 2014 Jul;35(7):1778.e9-1778.e23. doi: 10.1016/j.neurobiolaging.2014.01.014. Epub 2014 Jan 17.
• [2] Integrative omics data analyses of repeated dose toxicity of valproic acid in vitro reveal new mechanisms of steatosis induction. Toxicology. 2018 Jan 15;393:160-170.
• [3] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [4] Blood transcript immune signatures distinguish a subset of people with elevated serum ALT from others given acetaminophen. Clin Pharmacol Ther. 2016 Apr;99(4):432-41.
• [5] Bringing in vitro analysis closer to in vivo: studying doxorubicin toxicity and associated mechanisms in 3D human microtissues with PBPK-based dose modelling. Toxicol Lett. 2018 Sep 15;294:184-192.
• [6] 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.
• [7] The exosome-like vesicles derived from androgen exposed-prostate stromal cells promote epithelial cells proliferation and epithelial-mesenchymal transition. Toxicol Appl Pharmacol. 2021 Jan 15;411:115384. doi: 10.1016/j.taap.2020.115384. Epub 2020 Dec 25.
• [8] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [9] 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.
• [10] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [11] Identification by automated screening of a small molecule that selectively eliminates neural stem cells derived from hESCs but not dopamine neurons. PLoS One. 2009 Sep 23;4(9):e7155.
• [12] 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.
• [13] DNA methylome-wide alterations associated with estrogen receptor-dependent effects of bisphenols in breast cancer. Clin Epigenetics. 2019 Oct 10;11(1):138. doi: 10.1186/s13148-019-0725-y.
• [14] Identification of transcriptome signatures and biomarkers specific for potential developmental toxicants inhibiting human neural crest cell migration. Arch Toxicol. 2016 Jan;90(1):159-80.
• [15] Transcriptome and DNA methylation changes modulated by sulforaphane induce cell cycle arrest, apoptosis, DNA damage, and suppression of proliferation in human liver cancer cells. Food Chem Toxicol. 2020 Feb;136:111047. doi: 10.1016/j.fct.2019.111047. Epub 2019 Dec 12.