Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT7QLDU4)

• DOT Name: Probable E3 ubiquitin-protein ligase DTX2 (DTX2)
• Synonyms: EC 2.3.2.27; Protein deltex-2; Deltex2; hDTX2; RING finger protein 58; RING-type E3 ubiquitin transferase DTX2
• Gene Name: DTX2
• Related Disease:
  Acute myelogenous leukaemia
  leukaemia
  Leukemia
  Brain cancer
  Brain neoplasm
• UniProt ID: DTX2_HUMAN
• PDB ID: 6IR0; 6Y22; 6Y2X; 6Y3J
• EC Number: 2.3.2.27
• Pfam ID: PF18102 ; PF02825 ; PF00097
• Sequence:
  MAMAPSPSLVQVYTSPAAVAVWEWQDGLGTWHPYSATVCSFIEQQFVQQKGQRFGLGSLA
  HSIPLGQADPSLAPYIIDLPSWTQFRQDTGTMRAVRRHLFPQHSAPGRGVVWEWLSDDGS
  WTAYEASVCDYLEQQVARGNQLVDLAPLGYNYTVNYTTHTQTNKTSSFCRSVRRQAGPPY
  PVTTIIAPPGHTGVACSCHQCLSGSRTGPVSGRYRHSMTNLPAYPVPQHPPHRTASVFGT
  HQAFAPYNKPSLSGARSAPRLNTTNAWGAAPPSLGSQPLYRSSLSHLGPQHLPPGSSTSG
  AVSASLPSGPSSSPGSVPATVPMQMPKPSRVQQALAGMTSVLMSAIGLPVCLSRAPQPTS
  PPASRLASKSHGSVKRLRKMSVKGATPKPEPEPEQVIKNYTEELKVPPDEDCIICMEKLS
  TASGYSDVTDSKAIGSLAVGHLTKCSHAFHLLCLLAMYCNGNKDGSLQCPSCKTIYGEKT
  GTQPQGKMEVLRFQMSLPGHEDCGTILIVYSIPHGIQGPEHPNPGKPFTARGFPRQCYLP
  DNAQGRKVLELLKVAWKRRLIFTVGTSSTTGETDTVVWNEIHHKTEMDRNITGHGYPDPN
  YLQNVLAELAAQGVTEDCLEQQ
• Function: Regulator of Notch signaling, a signaling pathway involved in cell-cell communications that regulates a broad spectrum of cell-fate determinations. Probably acts both as a positive and negative regulator of Notch, depending on the developmental and cell context. Mediates the antineural activity of Notch, possibly by inhibiting the transcriptional activation mediated by MATCH1. Functions as a ubiquitin ligase protein in vitro, suggesting that it may regulate the Notch pathway via some ubiquitin ligase activity.
• KEGG Pathway: Notch sig.ling pathway (hsa04330)
• Reactome Pathway: Activated NOTCH1 Transmits Signal to the Nucleus (R-HSA-2122948)

Molecular Interaction Atlas (MIA) of This DOT

5 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Acute myelogenous leukaemia	DISCSPTN	Definitive	Genetic Variation	[1]
leukaemia	DISS7D1V	Definitive	Genetic Variation	[1]
Leukemia	DISNAKFL	Definitive	Genetic Variation	[1]
Brain cancer	DISBKFB7	Strong	Biomarker	[2]
Brain neoplasm	DISY3EKS	Strong	Biomarker	[2]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Enzalutamide	DMGL19D	Approved	Enzalutamide affects the expression of Probable E3 ubiquitin-protein ligase DTX2 (DTX2).	[3]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Probable E3 ubiquitin-protein ligase DTX2 (DTX2).	[4]

References

• [1] Acute myeloid leukemia with t(7;21)(q11.2;q22) expresses a novel, reversed-sequence RUNX1-DTX2 chimera.Int J Hematol. 2012 Aug;96(2):268-73. doi: 10.1007/s12185-012-1112-z. Epub 2012 Jun 4.
• [2] Inhibition of notch signaling blocks growth of glioblastoma cell lines and tumor neurospheres.Genes Cancer. 2010 Aug;1(8):822-35. doi: 10.1177/1947601910383564.
• [3] NOTCH signaling is activated in and contributes to resistance in enzalutamide-resistant prostate cancer cells. J Biol Chem. 2019 May 24;294(21):8543-8554. doi: 10.1074/jbc.RA118.006983. Epub 2019 Apr 2.
• [4] 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.