Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTOHZG1O)

• DOT Name: All-trans retinoic acid-induced differentiation factor (ATRAID)
• Synonyms: Apoptosis-related protein 3; APR-3; p18
• Gene Name: ATRAID
• UniProt ID: ARAID_HUMAN
• Sequence:
  MAPHDPGSLTTLVPWAAALLLALGVERALALPEICTQCPGSVQNLSKVAFYCKTTRELML
  HARCCLNQKGTILGLDLQNCSLEDPGPNFHQAHTTVIIDLQANPLKGDLANTFRGFTQLQ
  TLILPQHVNCPGGINAWNTITSYIDNQICQGQKNLCNNTGDPEMCPENGSCVPDGPGLLQ
  CVCADGFHGYKCMRQGSFSLLMFFGILGATTLSVSILLWATQRRKAKTS
• Function: Promotes osteoblast cell differentiation and terminal mineralization. Plays a role in inducing the cell cycle arrest via inhibiting CCND1 expression in all-trans-retinoic acid (ATRA) signal pathway. In osteoclasts, forms a transporter complex with ATRAID for nitrogen-containing-bisphophonates (N-BPs) required for releasing N-BP molecules that have trafficked to lysosomes through fluid-phase endocytosis into the cytosol.
• Tissue Specificity: Weakly expressed in hematopoietic cell lines.

Molecular Interaction Atlas (MIA) of This DOT

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the methylation of All-trans retinoic acid-induced differentiation factor (ATRAID).	[1]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of All-trans retinoic acid-induced differentiation factor (ATRAID).	[6]

7 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 All-trans retinoic acid-induced differentiation factor (ATRAID).	[2]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of All-trans retinoic acid-induced differentiation factor (ATRAID).	[3]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of All-trans retinoic acid-induced differentiation factor (ATRAID).	[4]
Aspirin	DM672AH	Approved	Aspirin decreases the expression of All-trans retinoic acid-induced differentiation factor (ATRAID).	[5]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of All-trans retinoic acid-induced differentiation factor (ATRAID).	[7]
chloropicrin	DMSGBQA	Investigative	chloropicrin increases the expression of All-trans retinoic acid-induced differentiation factor (ATRAID).	[8]
Deguelin	DMXT7WG	Investigative	Deguelin increases the expression of All-trans retinoic acid-induced differentiation factor (ATRAID).	[9]

References

• [1] 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.
• [2] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [3] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [4] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [5] Expression profile analysis of human peripheral blood mononuclear cells in response to aspirin. Arch Immunol Ther Exp (Warsz). 2005 Mar-Apr;53(2):151-8.
• [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] Bromodomain-containing protein 4 (BRD4) regulates RNA polymerase II serine 2 phosphorylation in human CD4+ T cells. J Biol Chem. 2012 Dec 14;287(51):43137-55.
• [8] Transcriptomic analysis of human primary bronchial epithelial cells after chloropicrin treatment. Chem Res Toxicol. 2015 Oct 19;28(10):1926-35.
• [9] Neurotoxicity and underlying cellular changes of 21 mitochondrial respiratory chain inhibitors. Arch Toxicol. 2021 Feb;95(2):591-615. doi: 10.1007/s00204-020-02970-5. Epub 2021 Jan 29.