Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTDKB4DQ)

• DOT Name: Ethanolamine kinase 1 (ETNK1)
• Synonyms: EKI 1; EC 2.7.1.82
• Gene Name: ETNK1
• Related Disease:
  Chronic myelomonocytic leukaemia
  Chronic myelomonocytic leukemia
  Juvenile idiopathic arthritis
  Myelodysplastic/myeloproliferative neoplasm
  Refractory chronic myeloid leukaemia
  Seminoma
  Systemic mastocytosis
  Neoplasm
• UniProt ID: EKI1_HUMAN
• EC Number: 2.7.1.82
• Pfam ID: PF01633
• Sequence:
  MLCGRPRSSSDNRNFLRERAGLSSAAVQTRIGNSAASRRSPAARPPVPAPPALPRGRPGT
  EGSTSLSAPAVLVVAVAVVVVVVSAVAWAMANYIHVPPGSPEVPKLNVTVQDQEEHRCRE
  GALSLLQHLRPHWDPQEVTLQLFTDGITNKLIGCYVGNTMEDVVLVRIYGNKTELLVDRD
  EEVKSFRVLQAHGCAPQLYCTFNNGLCYEFIQGEALDPKHVCNPAIFRLIARQLAKIHAI
  HAHNGWIPKSNLWLKMGKYFSLIPTGFADEDINKRFLSDIPSSQILQEEMTWMKEILSNL
  GSPVVLCHNDLLCKNIIYNEKQGDVQFIDYEYSGYNYLAYDIGNHFNEFAGVSDVDYSLY
  PDRELQSQWLRAYLEAYKEFKGFGTEVTEKEVEILFIQVNQFALASHFFWGLWALIQAKY
  STIEFDFLGYAIVRFNQYFKMKPEVTALKVPE
• Function: Highly specific for ethanolamine phosphorylation. May be a rate-controlling step in phosphatidylethanolamine biosynthesis.
• Tissue Specificity: Expressed in kidney, liver, placenta, heart, leukocyte, ovary and testis.
• KEGG Pathway:
  Glycerophospholipid metabolism (hsa00564)
  Metabolic pathways (hsa01100)
• Reactome Pathway: Synthesis of PE (R-HSA-1483213)
• BioCyc Pathway: MetaCyc:HS06586-MONOMER

Molecular Interaction Atlas (MIA) of This DOT

8 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Chronic myelomonocytic leukaemia	DISDN5P7	Strong	Genetic Variation	[1]
Chronic myelomonocytic leukemia	DISIL8UR	Strong	Genetic Variation	[1]
Juvenile idiopathic arthritis	DISQZGBV	Strong	Biomarker	[2]
Myelodysplastic/myeloproliferative neoplasm	DISDHXQ4	Strong	Genetic Variation	[3]
Refractory chronic myeloid leukaemia	DIS40YPP	Strong	Genetic Variation	[3]
Seminoma	DIS3J8LJ	Strong	Genetic Variation	[4]
Systemic mastocytosis	DISNQ2OY	Strong	Genetic Variation	[1]
Neoplasm	DISZKGEW	Limited	Biomarker	[5]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the expression of Ethanolamine kinase 1 (ETNK1).	[6]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Ethanolamine kinase 1 (ETNK1).	[7]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Ethanolamine kinase 1 (ETNK1).	[8]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Ethanolamine kinase 1 (ETNK1).	[9]
Vorinostat	DMWMPD4	Approved	Vorinostat increases the expression of Ethanolamine kinase 1 (ETNK1).	[10]
Panobinostat	DM58WKG	Approved	Panobinostat increases the expression of Ethanolamine kinase 1 (ETNK1).	[10]
Isotretinoin	DM4QTBN	Approved	Isotretinoin decreases the expression of Ethanolamine kinase 1 (ETNK1).	[11]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of Ethanolamine kinase 1 (ETNK1).	[12]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Ethanolamine kinase 1 (ETNK1).	[10]
Afimoxifene	DMFORDT	Phase 2	Afimoxifene increases the expression of Ethanolamine kinase 1 (ETNK1).	[13]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of Ethanolamine kinase 1 (ETNK1).	[14]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Ethanolamine kinase 1 (ETNK1).	[15]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Ethanolamine kinase 1 (ETNK1).	[16]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Ethanolamine kinase 1 (ETNK1).	[18]
Milchsaure	DM462BT	Investigative	Milchsaure increases the expression of Ethanolamine kinase 1 (ETNK1).	[19]
Coumestrol	DM40TBU	Investigative	Coumestrol decreases the expression of Ethanolamine kinase 1 (ETNK1).	[20]
Deguelin	DMXT7WG	Investigative	Deguelin decreases the expression of Ethanolamine kinase 1 (ETNK1).	[21]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Ethanolamine kinase 1 (ETNK1).	[17]

References

• [1] Novel recurrent mutations in ethanolamine kinase 1 (ETNK1) gene in systemic mastocytosis with eosinophilia and chronic myelomonocytic leukemia.Blood Cancer J. 2015 Jan 23;5(1):e275. doi: 10.1038/bcj.2014.94.
• [2] Gene expression signatures in polyarticular juvenile idiopathic arthritis demonstrate disease heterogeneity and offer a molecular classification of disease subsets.Arthritis Rheum. 2009 Jul;60(7):2113-23. doi: 10.1002/art.24534.
• [3] Recurrent ETNK1 mutations in atypical chronic myeloid leukemia.Blood. 2015 Jan 15;125(3):499-503. doi: 10.1182/blood-2014-06-579466. Epub 2014 Oct 24.
• [4] Coamplification of DAD-R, SOX5, and EKI1 in human testicular seminomas, with specific overexpression of DAD-R, correlates with reduced levels of apoptosis and earlier clinical manifestation.Cancer Res. 2002 Mar 15;62(6):1822-31.
• [5] Importance of epidermal growth factor receptor signaling in establishment of adenomas and maintenance of carcinomas during intestinal tumorigenesis.Proc Natl Acad Sci U S A. 2002 Feb 5;99(3):1521-6. doi: 10.1073/pnas.032678499. Epub 2002 Jan 29.
• [6] Definition of transcriptome-based indices for quantitative characterization of chemically disturbed stem cell development: introduction of the STOP-Toxukn and STOP-Toxukk tests. Arch Toxicol. 2017 Feb;91(2):839-864.
• [7] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [8] 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.
• [9] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [10] A transcriptome-based classifier to identify developmental toxicants by stem cell testing: design, validation and optimization for histone deacetylase inhibitors. Arch Toxicol. 2015 Sep;89(9):1599-618.
• [11] Temporal changes in gene expression in the skin of patients treated with isotretinoin provide insight into its mechanism of action. Dermatoendocrinol. 2009 May;1(3):177-87.
• [12] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [13] Gene expression preferentially regulated by tamoxifen in breast cancer cells and correlations with clinical outcome. Cancer Res. 2006 Jul 15;66(14):7334-40.
• [14] New insights into BaP-induced toxicity: role of major metabolites in transcriptomics and contribution to hepatocarcinogenesis. Arch Toxicol. 2016 Jun;90(6):1449-58.
• [15] 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.
• [16] 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.
• [17] DNA methylome-wide alterations associated with estrogen receptor-dependent effects of bisphenols in breast cancer. Clin Epigenetics. 2019 Oct 10;11(1):138. doi: 10.1186/s13148-019-0725-y.
• [18] 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.
• [19] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.
• [20] Pleiotropic combinatorial transcriptomes of human breast cancer cells exposed to mixtures of dietary phytoestrogens. Food Chem Toxicol. 2009 Apr;47(4):787-95.
• [21] 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.