Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT56Y83S)

• DOT Name: Protein delta homolog 2 (DLK2)
• Synonyms: DLK-2; Epidermal growth factor-like protein 9; EGF-like protein 9
• Gene Name: DLK2
• Related Disease:
  Advanced cancer
  Breast cancer
  Breast carcinoma
  Breast neoplasm
  Triple negative breast cancer
  Uveal Melanoma
  Anxiety
  Anxiety disorder
  Neoplasm
• UniProt ID: DLK2_HUMAN
• Pfam ID: PF21700 ; PF00008
• Sequence:
  MPSGCRCLHLVCLLCILGAPGQPVRADDCSSHCDLAHGCCAPDGSCRCDPGWEGLHCERC
  VRMPGCQHGTCHQPWQCICHSGWAGKFCDKDEHICTTQSPCQNGGQCMYDGGGEYHCVCL
  PGFHGRDCERKAGPCEQAGSPCRNGGQCQDDQGFALNFTCRCLVGFVGARCEVNVDDCLM
  RPCANGATCLDGINRFSCLCPEGFAGRFCTINLDDCASRPCQRGARCRDRVHDFDCLCPS
  GYGGKTCELVLPVPDPPTTVDTPLGPTSAVVVPATGPAPHSAGAGLLRISVKEVVRRQEA
  GLGEPSLVALVVFGALTAALVLATVLLTLRAWRRGVCPPGPCCYPAPHYAPACQDQECQV
  SMLPAGLPLPRDLPPEPGKTTAL
• Function: Regulates adipogenesis.

Molecular Interaction Atlas (MIA) of This DOT

9 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Advanced cancer	DISAT1Z9	Strong	Biomarker	[1]
Breast cancer	DIS7DPX1	Strong	Biomarker	[1]
Breast carcinoma	DIS2UE88	Strong	Biomarker	[1]
Breast neoplasm	DISNGJLM	Strong	Altered Expression	[1]
Triple negative breast cancer	DISAMG6N	Strong	Biomarker	[1]
Uveal Melanoma	DISA7ZGL	Strong	Genetic Variation	[2]
Anxiety	DISIJDBA	Limited	Genetic Variation	[3]
Anxiety disorder	DISBI2BT	Limited	Genetic Variation	[3]
Neoplasm	DISZKGEW	Limited	Biomarker	[4]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the methylation of Protein delta homolog 2 (DLK2).	[5]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Calcitriol	DM8ZVJ7	Approved	Calcitriol decreases the expression of Protein delta homolog 2 (DLK2).	[6]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Protein delta homolog 2 (DLK2).	[7]
Amiodarone	DMUTEX3	Phase 2/3 Trial	Amiodarone increases the expression of Protein delta homolog 2 (DLK2).	[8]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of Protein delta homolog 2 (DLK2).	[9]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Protein delta homolog 2 (DLK2).	[10]
Sulforaphane	DMQY3L0	Investigative	Sulforaphane decreases the expression of Protein delta homolog 2 (DLK2).	[11]

References

• [1] EGFL9 promotes breast cancer metastasis by inducing cMET activation and metabolic reprogramming.Nat Commun. 2019 Nov 6;10(1):5033. doi: 10.1038/s41467-019-13034-3.
• [2] Comprehensive Genetic Landscape of Uveal Melanoma by Whole-Genome Sequencing.Am J Hum Genet. 2016 Nov 3;99(5):1190-1198. doi: 10.1016/j.ajhg.2016.09.008. Epub 2016 Oct 13.
• [3] Deletion of Dlk2 increases the vulnerability to anxiety-like behaviors and impairs the anxiolytic action of alprazolam.Psychoneuroendocrinology. 2017 Nov;85:134-141. doi: 10.1016/j.psyneuen.2017.08.015. Epub 2017 Aug 31.
• [4] Therapeutic efficacy of combined vaccination against tumor pericyte-associated antigens DLK1 and DLK2 in mice.Oncoimmunology. 2017 Feb 10;6(3):e1290035. doi: 10.1080/2162402X.2017.1290035. eCollection 2017.
• [5] 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.
• [6] Large-scale in silico and microarray-based identification of direct 1,25-dihydroxyvitamin D3 target genes. Mol Endocrinol. 2005 Nov;19(11):2685-95.
• [7] Gene Expression Regulation and Pathway Analysis After Valproic Acid and Carbamazepine Exposure in a Human Embryonic Stem Cell-Based Neurodevelopmental Toxicity Assay. Toxicol Sci. 2015 Aug;146(2):311-20. doi: 10.1093/toxsci/kfv094. Epub 2015 May 15.
• [8] Identification by automated screening of a small molecule that selectively eliminates neural stem cells derived from hESCs but not dopamine neurons. PLoS One. 2009 Sep 23;4(9):e7155.
• [9] Identification of a transcriptomic signature of food-relevant genotoxins in human HepaRG hepatocarcinoma cells. Food Chem Toxicol. 2020 Jun;140:111297. doi: 10.1016/j.fct.2020.111297. Epub 2020 Mar 28.
• [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] 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.