Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTOX5H49)

• DOT Name: Zinc finger protein Aiolos (IKZF3)
• Synonyms: Ikaros family zinc finger protein 3
• Gene Name: IKZF3
• Related Disease: Immunodeficiency 84
• UniProt ID: IKZF3_HUMAN
• Pfam ID: PF00096
• Sequence:
  MEDIQTNAELKSTQEQSVPAESAAVLNDYSLTKSHEMENVDSGEGPANEDEDIGDDSMKV
  KDEYSERDENVLKSEPMGNAEEPEIPYSYSREYNEYENIKLERHVVSFDSSRPTSGKMNC
  DVCGLSCISFNVLMVHKRSHTGERPFQCNQCGASFTQKGNLLRHIKLHTGEKPFKCHLCN
  YACQRRDALTGHLRTHSVEKPYKCEFCGRSYKQRSSLEEHKERCRTFLQSTDPGDTASAE
  ARHIKAEMGSERALVLDRLASNVAKRKSSMPQKFIGEKRHCFDVNYNSSYMYEKESELIQ
  TRMMDQAINNAISYLGAEALRPLVQTPPAPTSEMVPVISSMYPIALTRAEMSNGAPQELE
  KKSIHLPEKSVPSERGLSPNNSGHDSTDTDSNHEERQNHIYQQNHMVLSRARNGMPLLKE
  VPRSYELLKPPPICPRDSVKVINKEGEVMDVYRCDHCRVLFLDYVMFTIHMGCHGFRDPF
  ECNMCGYRSHDRYEFSSHIARGEHRALLK
• Function: Transcription factor that plays an important role in the regulation of lymphocyte differentiation. Plays an essential role in regulation of B-cell differentiation, proliferation and maturation to an effector state. Involved in regulating BCL2 expression and controlling apoptosis in T-cells in an IL2-dependent manner.
• Tissue Specificity: Expressed most strongly in peripheral blood leukocytes, the spleen, and the thymus.

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Immunodeficiency 84	DISR3N2J	Strong	Autosomal dominant	[1]

3 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 Zinc finger protein Aiolos (IKZF3).	[2]
Decitabine	DMQL8XJ	Approved	Decitabine affects the methylation of Zinc finger protein Aiolos (IKZF3).	[5]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Zinc finger protein Aiolos (IKZF3).	[6]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Zinc finger protein Aiolos (IKZF3).	[3]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Zinc finger protein Aiolos (IKZF3).	[4]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Zinc finger protein Aiolos (IKZF3).	[7]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A affects the expression of Zinc finger protein Aiolos (IKZF3).	[5]

References

• [1] Lack of the transcriptional coactivator OBF-1 prevents the development of systemic lupus erythematosus-like phenotypes in Aiolos mutant mice. J Immunol. 2003 Feb 15;170(4):1699-706. doi: 10.4049/jimmunol.170.4.1699.
• [2] 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.
• [3] Transcriptional and Metabolic Dissection of ATRA-Induced Granulocytic Differentiation in NB4 Acute Promyelocytic Leukemia Cells. Cells. 2020 Nov 5;9(11):2423. doi: 10.3390/cells9112423.
• [4] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [5] Differential epigenetic regulation of Aiolos expression in human tumoral cell lines and primary cells. FEBS Lett. 2008 Feb 6;582(3):457-67. doi: 10.1016/j.febslet.2008.01.010. Epub 2008 Jan 17.
• [6] 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.
• [7] Inhibition of BRD4 attenuates tumor cell self-renewal and suppresses stem cell signaling in MYC driven medulloblastoma. Oncotarget. 2014 May 15;5(9):2355-71.