Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTR8LX4J)

• DOT Name: Retinoic acid-induced protein 2 (RAI2)
• Gene Name: RAI2
• Related Disease:
  Advanced cancer
  Colorectal carcinoma
  Estrogen-receptor positive breast cancer
  Nance-Horan syndrome
  Neoplasm
  Breast cancer
  Breast carcinoma
  Breast neoplasm
• UniProt ID: RAI2_HUMAN
• PDB ID: 8ARI; 8ATI
• Pfam ID: PF15279
• Sequence:
  MDDLQSQNLSMDMTDSPPALANNRLENGMAQLITTEAWNINSTDLVKKALVTVPAPSILN
  PPAESQSGMALKVAATVLQPLCLGESPVVMPIHMQVEGSSAPELNPNGNATYVMTTQGPV
  QLPVVLEQHVFQHLNSPLVLPQEAPCSSSTIHNNLFQGAEDPEAQPQLLDLRIPSQPQEP
  TLPFEAVLQNLFPSQGTLGPPPCQPPPGYAPVPPQPFSSPLSPLVPPATLLVPYPVIVPL
  PVPVPIPIPIPMPQSSESKFSSSFPKPPSSFGLHPFKGTQTPLEKDELKPFDILQPKEYF
  QLSRHTVIKMGSENEALDLSMKSVPWLKAGEVSPPIFQEDAALDLSVAAHRKSEPPPETL
  YDSGASVDSSGHTVMEKLPSGMEISFAPATSHEAPAMMDSHISSSDAATEMLSQPNHPSG
  EVKAENNIEMVGESQAAKVIVSVEDAVPTIFCGKIKGLSGVSTKNFSFKREDSVLQGYDI
  NSQGEESMGNAEPLRKPIKNRSIKLKKVNSQEIHMLPIKKQRLATFFPRK

Molecular Interaction Atlas (MIA) of This DOT

8 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Advanced cancer	DISAT1Z9	Strong	Altered Expression	[1]
Colorectal carcinoma	DIS5PYL0	Strong	Posttranslational Modification	[2]
Estrogen-receptor positive breast cancer	DIS1H502	Strong	Biomarker	[3]
Nance-Horan syndrome	DISSFYUP	Strong	Genetic Variation	[4]
Neoplasm	DISZKGEW	Strong	Biomarker	[2]
Breast cancer	DIS7DPX1	Limited	Altered Expression	[2]
Breast carcinoma	DIS2UE88	Limited	Altered Expression	[2]
Breast neoplasm	DISNGJLM	Limited	Biomarker	[1]

2 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 Retinoic acid-induced protein 2 (RAI2).	[5]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene affects the methylation of Retinoic acid-induced protein 2 (RAI2).	[14]

12 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 Retinoic acid-induced protein 2 (RAI2).	[6]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Retinoic acid-induced protein 2 (RAI2).	[7]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Retinoic acid-induced protein 2 (RAI2).	[8]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Retinoic acid-induced protein 2 (RAI2).	[9]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Retinoic acid-induced protein 2 (RAI2).	[10]
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of Retinoic acid-induced protein 2 (RAI2).	[11]
Testosterone	DM7HUNW	Approved	Testosterone increases the expression of Retinoic acid-induced protein 2 (RAI2).	[11]
Zoledronate	DMIXC7G	Approved	Zoledronate increases the expression of Retinoic acid-induced protein 2 (RAI2).	[12]
Dexamethasone	DMMWZET	Approved	Dexamethasone increases the expression of Retinoic acid-induced protein 2 (RAI2).	[13]
THAPSIGARGIN	DMDMQIE	Preclinical	THAPSIGARGIN decreases the expression of Retinoic acid-induced protein 2 (RAI2).	[15]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Retinoic acid-induced protein 2 (RAI2).	[16]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Retinoic acid-induced protein 2 (RAI2).	[17]

References

• [1] Suppression of early hematogenous dissemination of human breast cancer cells to bone marrow by retinoic Acid-induced 2.Cancer Discov. 2015 May;5(5):506-19. doi: 10.1158/2159-8290.CD-14-1042. Epub 2015 Feb 25.
• [2] Retinoic acid-induced 2 (RAI2) is a novel tumor suppressor, and promoter region methylation of RAI2 is a poor prognostic marker in colorectal cancer.Clin Epigenetics. 2018 May 23;10:69. doi: 10.1186/s13148-018-0501-4. eCollection 2018.
• [3] RAI2: Linking Retinoic Acid Signaling with Metastasis Suppression.Cancer Discov. 2015 May;5(5):466-8. doi: 10.1158/2159-8290.CD-15-0352.
• [4] Refinement of the X-linked cataract locus (CXN) and gene analysis for CXN and Nance-Horan syndrome (NHS).Ophthalmic Genet. 2004 Jun;25(2):121-31. doi: 10.1080/13816810490514360.
• [5] 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.
• [6] Comparison of HepG2 and HepaRG by whole-genome gene expression analysis for the purpose of chemical hazard identification. Toxicol Sci. 2010 May;115(1):66-79.
• [7] Development of a neural teratogenicity test based on human embryonic stem cells: response to retinoic acid exposure. Toxicol Sci. 2011 Dec;124(2):370-7.
• [8] 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.
• [9] 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.
• [10] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [11] Effects of 1alpha,25 dihydroxyvitamin D3 and testosterone on miRNA and mRNA expression in LNCaP cells. Mol Cancer. 2011 May 18;10:58.
• [12] Interleukin-19 as a translational indicator of renal injury. Arch Toxicol. 2015 Jan;89(1):101-6.
• [13] Identification of mechanisms of action of bisphenol a-induced human preadipocyte differentiation by transcriptional profiling. Obesity (Silver Spring). 2014 Nov;22(11):2333-43.
• [14] 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.
• [15] Chemical stresses fail to mimic the unfolded protein response resulting from luminal load with unfolded polypeptides. J Biol Chem. 2018 Apr 13;293(15):5600-5612.
• [16] Bisphenol A induces DSB-ATM-p53 signaling leading to cell cycle arrest, senescence, autophagy, stress response, and estrogen release in human fetal lung fibroblasts. Arch Toxicol. 2018 Apr;92(4):1453-1469.
• [17] From transient transcriptome responses to disturbed neurodevelopment: role of histone acetylation and methylation as epigenetic switch between reversible and irreversible drug effects. Arch Toxicol. 2014 Jul;88(7):1451-68.