Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT5S1Z75)

• DOT Name: Ethanolamine kinase 2 (ETNK2)
• Synonyms: EKI 2; EC 2.7.1.82; Ethanolamine kinase-like protein
• Gene Name: ETNK2
• UniProt ID: EKI2_HUMAN
• EC Number: 2.7.1.82
• Pfam ID: PF01633
• Sequence:
  MAVPPSAPQPRASFHLRRHTPCPQCSWGMEEKAAASASCREPPGPPRAAAVAYFGISVDP
  DDILPGALRLIQELRPHWKPEQVRTKRFTDGITNKLVACYVEEDMQDCVLVRVYGERTEL
  LVDRENEVRNFQLLRAHSCAPKLYCTFQNGLCYEYMQGVALEPEHIREPRLFRLIALEMA
  KIHTIHANGSLPKPILWHKMHNYFTLVKNEINPSLSADVPKVEVLERELAWLKEHLSQLE
  SPVVFCHNDLLCKNIIYDSIKGHVRFIDYEYAGYNYQAFDIGNHFNEFAGVNEVDYCLYP
  ARETQLQWLHYYLQAQKGMAVTPREVQRLYVQVNKFALASHFFWALWALIQNQYSTIDFD
  FLRYAVIRFNQYFKVKPQASALEMPK
• Function: Highly specific for ethanolamine phosphorylation. Does not have choline kinase activity.
• Tissue Specificity: Expressed in kidney, liver, ovary, testis and prostate.
• KEGG Pathway:
  Glycerophospholipid metabolism (hsa00564)
  Metabolic pathways (hsa01100)
• Reactome Pathway: Synthesis of PE (R-HSA-1483213)

Molecular Interaction Atlas (MIA) of This DOT

This DOT Affected the Drug Response of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
NAPQI	DM8F5LR	Investigative	Ethanolamine kinase 2 (ETNK2) affects the response to substance of NAPQI.	[13]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the expression of Ethanolamine kinase 2 (ETNK2).	[1]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Ethanolamine kinase 2 (ETNK2).	[2]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Ethanolamine kinase 2 (ETNK2).	[3]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Ethanolamine kinase 2 (ETNK2).	[4]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Ethanolamine kinase 2 (ETNK2).	[2]
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of Ethanolamine kinase 2 (ETNK2).	[5]
Troglitazone	DM3VFPD	Approved	Troglitazone decreases the expression of Ethanolamine kinase 2 (ETNK2).	[6]
Rosiglitazone	DMILWZR	Approved	Rosiglitazone decreases the expression of Ethanolamine kinase 2 (ETNK2).	[6]
Fenofibrate	DMFKXDY	Approved	Fenofibrate decreases the expression of Ethanolamine kinase 2 (ETNK2).	[6]
Resveratrol	DM3RWXL	Phase 3	Resveratrol increases the expression of Ethanolamine kinase 2 (ETNK2).	[7]
Genistein	DM0JETC	Phase 2/3	Genistein increases the expression of Ethanolamine kinase 2 (ETNK2).	[7]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Ethanolamine kinase 2 (ETNK2).	[9]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Ethanolamine kinase 2 (ETNK2).	[7]
Sulforaphane	DMQY3L0	Investigative	Sulforaphane decreases the expression of Ethanolamine kinase 2 (ETNK2).	[10]
Acetaldehyde	DMJFKG4	Investigative	Acetaldehyde increases the expression of Ethanolamine kinase 2 (ETNK2).	[11]
Butanoic acid	DMTAJP7	Investigative	Butanoic acid increases the expression of Ethanolamine kinase 2 (ETNK2).	[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 decreases the methylation of Ethanolamine kinase 2 (ETNK2).	[8]

References

• [1] Stem cell transcriptome responses and corresponding biomarkers that indicate the transition from adaptive responses to cytotoxicity. Chem Res Toxicol. 2017 Apr 17;30(4):905-922.
• [2] 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.
• [3] Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
• [4] 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.
• [5] Large-scale in silico and microarray-based identification of direct 1,25-dihydroxyvitamin D3 target genes. Mol Endocrinol. 2005 Nov;19(11):2685-95.
• [6] Transcriptomic analysis of untreated and drug-treated differentiated HepaRG cells over a 2-week period. Toxicol In Vitro. 2015 Dec 25;30(1 Pt A):27-35.
• [7] Gene expression profiling in Ishikawa cells: a fingerprint for estrogen active compounds. Toxicol Appl Pharmacol. 2009 Apr 1;236(1):85-96.
• [8] 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.
• [9] 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.
• [10] Transcriptome and DNA methylation changes modulated by sulforaphane induce cell cycle arrest, apoptosis, DNA damage, and suppression of proliferation in human liver cancer cells. Food Chem Toxicol. 2020 Feb;136:111047. doi: 10.1016/j.fct.2019.111047. Epub 2019 Dec 12.
• [11] Transcriptome profile analysis of saturated aliphatic aldehydes reveals carbon number-specific molecules involved in pulmonary toxicity. Chem Res Toxicol. 2014 Aug 18;27(8):1362-70.
• [12] MS4A3-HSP27 target pathway reveals potential for haematopoietic disorder treatment in alimentary toxic aleukia. Cell Biol Toxicol. 2023 Feb;39(1):201-216. doi: 10.1007/s10565-021-09639-4. Epub 2021 Sep 28.
• [13] Acetaminophen-NAPQI hepatotoxicity: a cell line model system genome-wide association study. Toxicol Sci. 2011 Mar;120(1):33-41. doi: 10.1093/toxsci/kfq375. Epub 2010 Dec 22.