Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT8Q5PVB)

• DOT Name: Ornithine decarboxylase antizyme 3 (OAZ3)
• Synonyms: AZ3; ODC-Az 3
• Gene Name: OAZ3
• Related Disease: Male infertility
• UniProt ID: OAZ3_HUMAN
• Pfam ID: PF02100
• Sequence:
  MPCKRCRPSVYSLSYIKRGKTRNYLYPIWSPYAYYLYCYKYRITLREKMLPRCYKSITYK
  EEEDLTLQPRSCLQCSESLVGLQEGKSTEQGNHDQLKELYSAGNLTVLATDPLLHQDPVQ
  LDFHFRLTSQTSAHWHGLLCDRRLFLDIPYQALDQGNRESLTATLEYVEEKTNVDSVFVN
  FQNDRNDRGALLRAFSYMGFEVVRPDHPALPPLDNVIFMVYPLERDVGHLPSEPP
• Function: Ornithine decarboxylase (ODC) antizyme protein that negatively regulates ODC activity and intracellular polyamine biosynthesis and uptake in response to increased intracellular polyamine levels. Binds to ODC monomers, inhibiting the assembly of the functional ODC homodimers. Does not target the ODC monomers for degradation, which allows a protein synthesis-independent restoration of ODC activity. Stabilizes AZIN2 by interfering with its ubiquitination. Involved in the translocation of AZNI2 from ER-Golgi intermediate compartment (ERGIC) to the cytosol. Probably plays a key role in spermatogenesis by regulating the intracellular concentration of polyamines in haploid germ cells.
• Tissue Specificity: Testis specific.
• Reactome Pathway: Regulation of ornithine decarboxylase (ODC) (R-HSA-350562)

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Male infertility	DISY3YZZ	Strong	Genetic Variation	[1]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Ornithine decarboxylase antizyme 3 (OAZ3).	[2]
Methotrexate	DM2TEOL	Approved	Methotrexate increases the expression of Ornithine decarboxylase antizyme 3 (OAZ3).	[4]
Niclosamide	DMJAGXQ	Approved	Niclosamide increases the expression of Ornithine decarboxylase antizyme 3 (OAZ3).	[5]
Afimoxifene	DMFORDT	Phase 2	Afimoxifene increases the expression of Ornithine decarboxylase antizyme 3 (OAZ3).	[6]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of Ornithine decarboxylase antizyme 3 (OAZ3).	[3]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Ornithine decarboxylase antizyme 3 (OAZ3).	[7]

References

• [1] Identification of polymorphisms and balancing selection in the male infertility candidate gene, ornithine decarboxylase antizyme 3.BMC Med Genet. 2006 Mar 16;7:27. doi: 10.1186/1471-2350-7-27.
• [2] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [3] Prenatal arsenic exposure and the epigenome: identifying sites of 5-methylcytosine alterations that predict functional changes in gene expression in newborn cord blood and subsequent birth outcomes. Toxicol Sci. 2015 Jan;143(1):97-106. doi: 10.1093/toxsci/kfu210. Epub 2014 Oct 10.
• [4] Global molecular effects of tocilizumab therapy in rheumatoid arthritis synovium. Arthritis Rheumatol. 2014 Jan;66(1):15-23.
• [5] Mitochondrial Uncoupling Induces Epigenome Remodeling and Promotes Differentiation in Neuroblastoma. Cancer Res. 2023 Jan 18;83(2):181-194. doi: 10.1158/0008-5472.CAN-22-1029.
• [6] Gene expression preferentially regulated by tamoxifen in breast cancer cells and correlations with clinical outcome. Cancer Res. 2006 Jul 15;66(14):7334-40.
• [7] 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.