Details of Drug Off-Target (DOT)

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

• DOT Name: Ras-associating and dilute domain-containing protein (RADIL)
• Gene Name: RADIL
• Related Disease:
  Advanced cancer
  Kidney cancer
  Pancreatic cancer
  Renal carcinoma
• UniProt ID: RADIL_HUMAN
• PDB ID: 1UM1; 3EC8
• Pfam ID: PF01843 ; PF00498 ; PF00595 ; PF00788
• Sequence:
  MFYGTHFIMSPPTKSKLKRQSQLLSSMLSRTLSYKYRDLDSTFSSLGASDDPAELSTQLS
  APGVLKVFGDSVCTGTHYKSVLATGTSSARELVKEALERYALDPRQAGQYVLCDVVGQAG
  DAGQRWQARCFRVFGDSEKPLLIQELWKPREGLSRRFELRKRSDVEELAAKEVDTITAGI
  NAQARRLQRSRAKGTPTPALGDARSSPPPRLRRTVSETSLSPVNALPAAAQGPEEPGPDA
  MRYSLYQSPHLLLLQGYSQQHDSLVYVLNRDRHTVGQRTPSSKPSISLSAPDILPLHCTI
  RRQPLPDSGQAAGRLVLEPIPGAHISVNFSEVGHRTVVLHHGDLLSLGLYYLLLFKDPAQ
  AQPLPARALARLRAVPQSCRLCGAALGARGAASPTQAALPRRQQLLLEFEPHLEDTLLQR
  IMTLIEPGGDDHKLTPAFLLCLCIQHSATHFQPGTFGQLLLKIARLIRETVWEKTKELAE
  KQAQLQEPISLASCAMADLVPDLQPILFWMSNSIELLYFIQQKCPLYMQSMEEQLDITGS
  KESLFSCTLTASEEAMAVLEEVVLYAFQQCVYYVSKSLYICLPALLECPPFQTERRESWS
  SAPELPEELRRVVSVYQAALDLLRQLQVHPEVASQMLAYLFFFSGTLLLNQLLDRGPSLS
  CFHWPRGVQACARLQQLLEWMRSAGFGAAGEHFFQKLSCTLNLLATPRAQLIQMSWTALR
  AAFPALSPAQLHRLLTHYQLASAMGPMSTWEPGAQDSPEAFRSEDVLESYENPPPIVLPS
  DGFQVDLEANCLDDSIYQHLLYVRHFLWGLRSRASPGSPGRPGSGASQPVCPEGMHHVVL
  DGHLEAPSCPLAPRDPGPAAREVAPERTLPLRGAPWAQAPPGRQPSRGGSQAGPPHTDSS
  CLLTPPSTPLGPEPGDPDWPESGGPCGKALPERQRNGLSGLRGAAPEGDSAALAEESPPA
  PSSRSSSTEDFCYVFTVELERGPSGLGMGLIDGMHTHLGAPGLYIQTLLPGSPAAADGRL
  SLGDRILEVNGSSLLGLGYLRAVDLIRHGGKKMRFLVAKSDVETAKKIHFRTPPL
• Function: Downstream effector of Rap required for cell adhesion and migration of neural crest precursors during development.
• KEGG Pathway: Adherens junction (hsa04520)

Molecular Interaction Atlas (MIA) of This DOT

4 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Advanced cancer	DISAT1Z9	Strong	Biomarker	[1]
Kidney cancer	DISBIPKM	Strong	Biomarker	[1]
Pancreatic cancer	DISJC981	Strong	Altered Expression	[1]
Renal carcinoma	DISER9XT	Strong	Biomarker	[1]

3 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 Ras-associating and dilute domain-containing protein (RADIL).	[2]
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of Ras-associating and dilute domain-containing protein (RADIL).	[4]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the methylation of Ras-associating and dilute domain-containing protein (RADIL).	[8]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Ras-associating and dilute domain-containing protein (RADIL).	[3]
Triclosan	DMZUR4N	Approved	Triclosan decreases the expression of Ras-associating and dilute domain-containing protein (RADIL).	[5]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of Ras-associating and dilute domain-containing protein (RADIL).	[6]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Ras-associating and dilute domain-containing protein (RADIL).	[7]

References

• [1] Rap GTPase Interactor: A Potential Marker for Cancer Prognosis Following Kidney Transplantation.Front Oncol. 2019 Aug 7;9:737. doi: 10.3389/fonc.2019.00737. eCollection 2019.
• [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] 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.
• [4] 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.
• [5] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [6] Benzo[a]pyrene-induced changes in microRNA-mRNA networks. Chem Res Toxicol. 2012 Apr 16;25(4):838-49.
• [7] Cell-based two-dimensional morphological assessment system to predict cancer drug-induced cardiotoxicity using human induced pluripotent stem cell-derived cardiomyocytes. Toxicol Appl Pharmacol. 2019 Nov 15;383:114761. doi: 10.1016/j.taap.2019.114761. Epub 2019 Sep 15.
• [8] 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.