Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTQETP8B)

• DOT Name: Protein ARK2N (ARK2N)
• Synonyms: ARKadia-like protein 1; Arkadia (RNF111) N-terminal like PKA signaling regulator protein 2N
• Gene Name: ARK2N
• UniProt ID: ARK2N_HUMAN
• Pfam ID: PF15303
• Sequence:
  MKMEEAVGKVEELIESEAPPKASEQETAKEEDGSVELESQVQKDGVADSTVISSMPCLLM
  ELRRDSSESQLASTESDKPTTGRVYESDSSNHCMLSPSSSGHLADSDTLSSAEENEPSQA
  ETAVEGDPSGVSGATVGRKSRRSRSESETSTMAAKKNRQSSDKQNGRVAKVKGHRSQKHK
  ERIRLLRQKREAAARKKYNLLQDSSTSDSDLTCDSSTSSSDDDEEVSGSSKTITAEIPDG
  PPVVAHYDMSDTNSDPEVVNVDNLLAAAVVQEHSNSVGGQDTGATWRTSGLLEELNAEAG
  HLDPGFLASDKTSAGNAPLNEEINIASSDSEVEIVGVQEHARCVHPRGGVIQSVSSWKHG
  SGTQYVSTRQTQSWTAVTPQQTWASPAEVVDLTLDEDSRRKYLL
• Function: AMPK substrate important for exercise capacity and skeletal muscle function. Required for normal contraction-induced signaling; (Microbial infection) Upon Epstein-Barr virus (EBV) infection, suppresses viral BZLF1 expression and subsequent EBV reactivation by interacting with JUN and inhibiting its transcriptional activitor activity on BZLF1 Z promoter.
• Tissue Specificity: Expressed in skeletal muscle.

Molecular Interaction Atlas (MIA) of This DOT

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the expression of Protein ARK2N (ARK2N).	[1]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Protein ARK2N (ARK2N).	[2]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Protein ARK2N (ARK2N).	[3]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Protein ARK2N (ARK2N).	[4]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Protein ARK2N (ARK2N).	[5]
Demecolcine	DMCZQGK	Approved	Demecolcine increases the expression of Protein ARK2N (ARK2N).	[6]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of Protein ARK2N (ARK2N).	[7]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of Protein ARK2N (ARK2N).	[8]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Protein ARK2N (ARK2N).	[10]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of Protein ARK2N (ARK2N).	[6]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
TAK-243	DM4GKV2	Phase 1	TAK-243 increases the sumoylation of Protein ARK2N (ARK2N).	[9]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 affects the phosphorylation of Protein ARK2N (ARK2N).	[11]
Coumarin	DM0N8ZM	Investigative	Coumarin decreases the phosphorylation of Protein ARK2N (ARK2N).	[11]

References

• [1] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [2] Gene expression analysis of precision-cut human liver slices indicates stable expression of ADME-Tox related genes. Toxicol Appl Pharmacol. 2011 May 15;253(1):57-69.
• [3] 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.
• [4] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [5] Quantitative proteomics reveals a broad-spectrum antiviral property of ivermectin, benefiting for COVID-19 treatment. J Cell Physiol. 2021 Apr;236(4):2959-2975. doi: 10.1002/jcp.30055. Epub 2020 Sep 22.
• [6] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
• [7] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [8] New insights into BaP-induced toxicity: role of major metabolites in transcriptomics and contribution to hepatocarcinogenesis. Arch Toxicol. 2016 Jun;90(6):1449-58.
• [9] Inhibiting ubiquitination causes an accumulation of SUMOylated newly synthesized nuclear proteins at PML bodies. J Biol Chem. 2019 Oct 18;294(42):15218-15234. doi: 10.1074/jbc.RA119.009147. Epub 2019 Jul 8.
• [10] 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.
• [11] 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.