Details of Drug Off-Target (DOT)

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

• DOT Name: Probable ATP-dependent RNA helicase DDX28 (DDX28)
• Synonyms: EC 3.6.4.13; Mitochondrial DEAD box protein 28
• Gene Name: DDX28
• UniProt ID: DDX28_HUMAN
• PDB ID: 7OI6
• EC Number: 3.6.4.13
• Pfam ID: PF00270 ; PF00271
• Sequence:
  MALTRPVRLFSLVTRLLLAPRRGLTVRSPDEPLPVVRIPVALQRQLEQRQSRRRNLPRPV
  LVRPGPLLVSARRPELNQPARLTLGRWERAPLASQGWKSRRARRDHFSIERAQQEAPAVR
  KLSSKGSFADLGLEPRVLHALQEAAPEVVQPTTVQSSTIPSLLRGRHVVCAAETGSGKTL
  SYLLPLLQRLLGQPSLDSLPIPAPRGLVLVPSRELAQQVRAVAQPLGRSLGLLVRDLEGG
  HGMRRIRLQLSRQPSADVLVATPGALWKALKSRLISLEQLSFLVLDEADTLLDESFLELV
  DYILEKSHIAEGPADLEDPFNPKAQLVLVGATFPEGVGQLLNKVASPDAVTTITSSKLHC
  IMPHVKQTFLRLKGADKVAELVHILKHRDRAERTGPSGTVLVFCNSSSTVNWLGYILDDH
  KIQHLRLQGQMPALMRVGIFQSFQKSSRDILLCTDIASRGLDSTGVELVVNYDFPPTLQD
  YIHRAGRVGRVGSEVPGTVISFVTHPWDVSLVQKIELAARRRRSLPGLASSVKEPLPQAT
• Function: Plays an essential role in facilitating the proper assembly of the mitochondrial large ribosomal subunit and its helicase activity is essential for this function. May be involved in RNA processing or transport. Has RNA and Mg(2+)-dependent ATPase activity.
• Tissue Specificity: Expressed in all tissues tested, including brain, placenta, lung, liver, skeletal muscle, kidney, pancreas, leukocytes, colon, small intestine, ovary and prostate.

Molecular Interaction Atlas (MIA) of This DOT

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 Probable ATP-dependent RNA helicase DDX28 (DDX28).	[1]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Probable ATP-dependent RNA helicase DDX28 (DDX28).	[2]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Probable ATP-dependent RNA helicase DDX28 (DDX28).	[3]
Cisplatin	DMRHGI9	Approved	Cisplatin affects the expression of Probable ATP-dependent RNA helicase DDX28 (DDX28).	[4]
Methotrexate	DM2TEOL	Approved	Methotrexate decreases the expression of Probable ATP-dependent RNA helicase DDX28 (DDX28).	[5]
Decitabine	DMQL8XJ	Approved	Decitabine affects the expression of Probable ATP-dependent RNA helicase DDX28 (DDX28).	[4]
Marinol	DM70IK5	Approved	Marinol decreases the expression of Probable ATP-dependent RNA helicase DDX28 (DDX28).	[6]
Teriflunomide	DMQ2FKJ	Approved	Teriflunomide decreases the expression of Probable ATP-dependent RNA helicase DDX28 (DDX28).	[7]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Probable ATP-dependent RNA helicase DDX28 (DDX28).	[8]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of Probable ATP-dependent RNA helicase DDX28 (DDX28).	[10]

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 Probable ATP-dependent RNA helicase DDX28 (DDX28).	[9]

References

• [1] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [2] Gene expression analysis of precision-cut human liver slices indicates stable expression of ADME-Tox related genes. Toxicol Appl Pharmacol. 2011 May 15;253(1):57-69.
• [3] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [4] Acute hypersensitivity of pluripotent testicular cancer-derived embryonal carcinoma to low-dose 5-aza deoxycytidine is associated with global DNA Damage-associated p53 activation, anti-pluripotency and DNA demethylation. PLoS One. 2012;7(12):e53003. doi: 10.1371/journal.pone.0053003. Epub 2012 Dec 27.
• [5] Global molecular effects of tocilizumab therapy in rheumatoid arthritis synovium. Arthritis Rheumatol. 2014 Jan;66(1):15-23.
• [6] THC exposure of human iPSC neurons impacts genes associated with neuropsychiatric disorders. Transl Psychiatry. 2018 Apr 25;8(1):89. doi: 10.1038/s41398-018-0137-3.
• [7] Mitochondrial dysfunction induced by leflunomide and its active metabolite. Toxicology. 2018 Mar 1;396-397:33-45.
• [8] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [9] 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.
• [10] Gene expression changes in primary human nasal epithelial cells exposed to formaldehyde in vitro. Toxicol Lett. 2010 Oct 5;198(2):289-95.