Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT4F47U6)

• DOT Name: AN1-type zinc finger protein 5
• Synonyms: Zinc finger A20 domain-containing protein 2; Zinc finger protein 216
• Gene Name: ZFAND5
• UniProt ID: ZFAN5_HUMAN
• PDB ID: 7QXW
• Pfam ID: PF01754 ; PF01428
• Sequence:
  MAQETNQTPGPMLCSTGCGFYGNPRTNGMCSVCYKEHLQRQQNSGRMSPMGTASGSNSPT
  SDSASVQRADTSLNNCEGAAGSTSEKSRNVPVAALPVTQQMTEMSISREDKITTPKTEVS
  EPVVTQPSPSVSQPSTSQSEEKAPELPKPKKNRCFMCRKKVGLTGFDCRCGNLFCGLHRY
  SDKHNCPYDYKAEAAAKIRKENPVVVAEKIQRI
• Function: Involved in protein degradation via the ubiquitin-proteasome system. May act by anchoring ubiquitinated proteins to the proteasome. Plays a role in ubiquitin-mediated protein degradation during muscle atrophy. Plays a role in the regulation of NF-kappa-B activation and apoptosis. Inhibits NF-kappa-B activation triggered by overexpression of RIPK1 and TRAF6 but not of RELA. Inhibits also tumor necrosis factor (TNF), IL-1 and TLR4-induced NF-kappa-B activation in a dose-dependent manner. Overexpression sensitizes cells to TNF-induced apoptosis. Is a potent inhibitory factor for osteoclast differentiation.
• Tissue Specificity: Highly expressed in skeletal muscle. Expressed in fetal cochlea. Also expressed in infant brain, fetal heart, pancreatic islet, melanocyte, pineal gland, placenta, corneal stroma, and parathyroid tumor. Weakly expressed or undetectable in adult brain, heart, colon, thymus, spleen, kidney, liver, small intestine, placenta, lung and peripheral blood leukocytes. Expressed in rhabdomyosarcoma RD cells (at protein level).

Molecular Interaction Atlas (MIA) of This DOT

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the methylation of AN1-type zinc finger protein 5.	[1]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 affects the phosphorylation of AN1-type zinc finger protein 5.	[15]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of AN1-type zinc finger protein 5.	[2]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of AN1-type zinc finger protein 5.	[3]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of AN1-type zinc finger protein 5.	[4]
Doxorubicin	DMVP5YE	Approved	Doxorubicin increases the expression of AN1-type zinc finger protein 5.	[5]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of AN1-type zinc finger protein 5.	[6]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide increases the expression of AN1-type zinc finger protein 5.	[7]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of AN1-type zinc finger protein 5.	[8]
Resveratrol	DM3RWXL	Phase 3	Resveratrol decreases the expression of AN1-type zinc finger protein 5.	[9]
Tocopherol	DMBIJZ6	Phase 2	Tocopherol decreases the expression of AN1-type zinc finger protein 5.	[10]
ACYLINE	DM9GRTK	Phase 2	ACYLINE increases the expression of AN1-type zinc finger protein 5.	[11]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of AN1-type zinc finger protein 5.	[12]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide increases the expression of AN1-type zinc finger protein 5.	[13]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of AN1-type zinc finger protein 5.	[14]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of AN1-type zinc finger protein 5.	[16]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of AN1-type zinc finger protein 5.	[17]
chloropicrin	DMSGBQA	Investigative	chloropicrin affects the expression of AN1-type zinc finger protein 5.	[18]

References

• [1] 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.
• [2] Comparison of HepG2 and HepaRG by whole-genome gene expression analysis for the purpose of chemical hazard identification. Toxicol Sci. 2010 May;115(1):66-79.
• [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] Predictive toxicology using systemic biology and liver microfluidic "on chip" approaches: application to acetaminophen injury. Toxicol Appl Pharmacol. 2012 Mar 15;259(3):270-80.
• [5] Bringing in vitro analysis closer to in vivo: studying doxorubicin toxicity and associated mechanisms in 3D human microtissues with PBPK-based dose modelling. Toxicol Lett. 2018 Sep 15;294:184-192.
• [6] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [7] Essential role of cell cycle regulatory genes p21 and p27 expression in inhibition of breast cancer cells by arsenic trioxide. Med Oncol. 2011 Dec;28(4):1225-54.
• [8] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [9] Differential expression of genes induced by resveratrol in LNCaP cells: P53-mediated molecular targets. Int J Cancer. 2003 Mar 20;104(2):204-12.
• [10] Selenium and vitamin E: cell type- and intervention-specific tissue effects in prostate cancer. J Natl Cancer Inst. 2009 Mar 4;101(5):306-20.
• [11] Intraprostatic androgens and androgen-regulated gene expression persist after testosterone suppression: therapeutic implications for castration-resistant prostate cancer. Cancer Res. 2007 May 15;67(10):5033-41.
• [12] Gene expression changes associated with altered growth and differentiation in benzo[a]pyrene or arsenic exposed normal human epidermal keratinocytes. J Appl Toxicol. 2008 May;28(4):491-508.
• [13] Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
• [14] 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.
• [15] Quantitative phosphoproteomics reveal cellular responses from caffeine, coumarin and quercetin in treated HepG2 cells. Toxicol Appl Pharmacol. 2022 Aug 15;449:116110. doi: 10.1016/j.taap.2022.116110. Epub 2022 Jun 7.
• [16] Epigenetic influences of low-dose bisphenol A in primary human breast epithelial cells. Toxicol Appl Pharmacol. 2010 Oct 15;248(2):111-21.
• [17] 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.
• [18] Transcriptomic analysis of human primary bronchial epithelial cells after chloropicrin treatment. Chem Res Toxicol. 2015 Oct 19;28(10):1926-35.