Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTYZGH63)

• DOT Name: 2-oxoglutarate and iron-dependent oxygenase JMJD4 (JMJD4)
• Synonyms: EC 1.14.11.-; JmjC domain-containing protein 4; Jumonji domain-containing protein 4; Lysyl-hydroxylase JMJD4
• Gene Name: JMJD4
• Related Disease: Colon adenocarcinoma
• UniProt ID: JMJD4_HUMAN
• EC Number: 1.14.11.-
• Pfam ID: PF02373
• Sequence:
  MDRETRALADSHFRGLGVDVPGVGQAPGRVAFVSEPGAFSYADFVRGFLLPNLPCVFSSA
  FTQGWGSRRRWVTPAGRPDFDHLLRTYGDVVVPVANCGVQEYNSNPKEHMTLRDYITYWK
  EYIQAGYSSPRGCLYLKDWHLCRDFPVEDVFTLPVYFSSDWLNEFWDALDVDDYRFVYAG
  PAGSWSPFHADIFRSFSWSVNVCGRKKWLLFPPGQEEALRDRHGNLPYDVTSPALCDTHL
  HPRNQLAGPPLEITQEAGEMVFVPSGWHHQVHNLDDTISINHNWVNGFNLANMWRFLQQE
  LCAVQEEVSEWRDSMPDWHHHCQVIMRSCSGINFEEFYHFLKVIAEKRLLVLREAAAEDG
  AGLGFEQAAFDVGRITEVLASLVAHPDFQRVDTSAFSPQPKELLQQLREAVDAAAAP
• Function: Catalyzes the 2-oxoglutarate and iron-dependent C4-lysyl hydroxylation of ETF1 at 'Lys-63' thereby promoting the translational termination efficiency of ETF1.
• Reactome Pathway: Protein hydroxylation (R-HSA-9629569)

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Colon adenocarcinoma	DISDRE0J	Limited	Altered Expression	[1]

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 2-oxoglutarate and iron-dependent oxygenase JMJD4 (JMJD4).	[2]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of 2-oxoglutarate and iron-dependent oxygenase JMJD4 (JMJD4).	[3]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of 2-oxoglutarate and iron-dependent oxygenase JMJD4 (JMJD4).	[4]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of 2-oxoglutarate and iron-dependent oxygenase JMJD4 (JMJD4).	[5]
Marinol	DM70IK5	Approved	Marinol decreases the expression of 2-oxoglutarate and iron-dependent oxygenase JMJD4 (JMJD4).	[6]
Fluorouracil	DMUM7HZ	Approved	Fluorouracil decreases the expression of 2-oxoglutarate and iron-dependent oxygenase JMJD4 (JMJD4).	[7]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of 2-oxoglutarate and iron-dependent oxygenase JMJD4 (JMJD4).	[8]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of 2-oxoglutarate and iron-dependent oxygenase JMJD4 (JMJD4).	[10]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of 2-oxoglutarate and iron-dependent oxygenase JMJD4 (JMJD4).	[11]
GALLICACID	DM6Y3A0	Investigative	GALLICACID increases the expression of 2-oxoglutarate and iron-dependent oxygenase JMJD4 (JMJD4).	[12]

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 affects the methylation of 2-oxoglutarate and iron-dependent oxygenase JMJD4 (JMJD4).	[9]

References

• [1] Correlation between high expression levels of jumonji domain-containing 4 and short survival in cases of colon adenocarcinoma.Biochem Biophys Res Commun. 2018 Sep 10;503(3):1442-1449. doi: 10.1016/j.bbrc.2018.07.061. Epub 2018 Jul 17.
• [2] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [3] Phenotypic characterization of retinoic acid differentiated SH-SY5Y cells by transcriptional profiling. PLoS One. 2013 May 28;8(5):e63862.
• [4] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [5] 17-Estradiol Activates HSF1 via MAPK Signaling in ER-Positive Breast Cancer Cells. Cancers (Basel). 2019 Oct 11;11(10):1533. doi: 10.3390/cancers11101533.
• [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] New insights into the mechanisms underlying 5-fluorouracil-induced intestinal toxicity based on transcriptomic and metabolomic responses in human intestinal organoids. Arch Toxicol. 2021 Aug;95(8):2691-2718. doi: 10.1007/s00204-021-03092-2. Epub 2021 Jun 20.
• [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] 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.
• [11] Identification of mechanisms of action of bisphenol a-induced human preadipocyte differentiation by transcriptional profiling. Obesity (Silver Spring). 2014 Nov;22(11):2333-43.
• [12] Gene expression profile analysis of gallic acid-induced cell death process. Sci Rep. 2021 Aug 18;11(1):16743. doi: 10.1038/s41598-021-96174-1.