Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTZD4JUO)

• DOT Name: Ankyrin repeat domain-containing protein 16 (ANKRD16)
• Gene Name: ANKRD16
• Related Disease:
  IgA nephropathy
  Acute myelogenous leukaemia
• UniProt ID: ANR16_HUMAN
• Pfam ID: PF00023 ; PF12796
• Sequence:
  MAQPGDPRRLCRLVQEGRLRALKEELQAAGGCPGPAGDTLLHCAARHGHRDVLAYLAEAW
  GMDIEATNRDYKRPLHEAASMGHRDCVRYLLGRGAAVDCLKKADWTPLMMACTRKNLGVI
  QELVEHGANPLLKNKDGWNSFHIASREGDPLILQYLLTVCPGAWKTESKIRRTPLHTAAM
  HGHLEAVKVLLKRCQYEPDYRDNCGVTALMDAIQCGHIDVARLLLDEHGACLSAEDSLGA
  QALHRAAVTGQDEAIRFLVSELGVDVDVRATSTHLTALHYAAKEGHTSTIQTLLSLGADI
  NSKDEKNRSALHLACAGQHLACAKFLLQSGLKDSEDITGTLAQQLPRRADVLQGSGHSAM
  T
• Function: Required to prevent the misactivation of serine (Ser) with tRNA(Ala) by promoting the hydrolysis of Ser-mischarged tRNA(Ala), thereby playing a role in translational fidelity. Binds directly to the catalytic domain of AARS/AlaRS and captures Ser that is misactivated by AARS/AlaRS, preventing the charging of Ser adenylates to tRNA(Ala) and precluding Ser misincorporation in nascent peptides.

Molecular Interaction Atlas (MIA) of This DOT

2 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
IgA nephropathy	DISZ8MTK	Strong	Genetic Variation	[1]
Acute myelogenous leukaemia	DISCSPTN	Limited	Genetic Variation	[2]

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 Ankyrin repeat domain-containing protein 16 (ANKRD16).	[3]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Ankyrin repeat domain-containing protein 16 (ANKRD16).	[4]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Ankyrin repeat domain-containing protein 16 (ANKRD16).	[5]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Ankyrin repeat domain-containing protein 16 (ANKRD16).	[6]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Ankyrin repeat domain-containing protein 16 (ANKRD16).	[7]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Ankyrin repeat domain-containing protein 16 (ANKRD16).	[8]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of Ankyrin repeat domain-containing protein 16 (ANKRD16).	[9]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Ankyrin repeat domain-containing protein 16 (ANKRD16).	[10]
Methotrexate	DM2TEOL	Approved	Methotrexate decreases the expression of Ankyrin repeat domain-containing protein 16 (ANKRD16).	[11]
Genistein	DM0JETC	Phase 2/3	Genistein decreases the expression of Ankyrin repeat domain-containing protein 16 (ANKRD16).	[12]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide decreases the expression of Ankyrin repeat domain-containing protein 16 (ANKRD16).	[13]

References

• [1] Genome-wide association study identifies new susceptible loci of IgA nephropathy in Koreans.BMC Med Genomics. 2019 Aug 19;12(1):122. doi: 10.1186/s12920-019-0568-6.
• [2] Genome-wide haplotype association study identify the FGFR2 gene as a risk gene for acute myeloid leukemia.Oncotarget. 2017 Jan 31;8(5):7891-7899. doi: 10.18632/oncotarget.13631.
• [3] 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.
• [4] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [5] 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.
• [6] 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.
• [7] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [8] Comparison of phenotypic and transcriptomic effects of false-positive genotoxins, true genotoxins and non-genotoxins using HepG2 cells. Mutagenesis. 2011 Sep;26(5):593-604.
• [9] Global gene expression analysis reveals differences in cellular responses to hydroxyl- and superoxide anion radical-induced oxidative stress in caco-2 cells. Toxicol Sci. 2010 Apr;114(2):193-203. doi: 10.1093/toxsci/kfp309. Epub 2009 Dec 31.
• [10] 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.
• [11] Global molecular effects of tocilizumab therapy in rheumatoid arthritis synovium. Arthritis Rheumatol. 2014 Jan;66(1):15-23.
• [12] The molecular basis of genistein-induced mitotic arrest and exit of self-renewal in embryonal carcinoma and primary cancer cell lines. BMC Med Genomics. 2008 Oct 10;1:49.
• [13] Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.