Details of Drug Off-Target (DOT)

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

• DOT Name: Uncharacterized aarF domain-containing protein kinase 2 (ADCK2)
• Synonyms: EC 2.7.11.-
• Gene Name: ADCK2
• Related Disease: Mitochondrial myopathy
• UniProt ID: ADCK2_HUMAN
• EC Number: 2.7.11.-
• Pfam ID: PF03109
• Sequence:
  MVAPWRVSVRVCLSHLRCFELRQGLSLLRPSECPRDARLCWLLLGTLPKVVSLCGDVGEG
  APDVLSRRRVRCSGAAGAGPAESLPRAGPLGGVFLHLRLWLRAGALLVKFFPLLLLYPLT
  YLAPSVSTLWLHLLLKATETSGPTYIKLGQWASTRRDLFSEAFCAQFSKLHVRVTPHPWT
  HTERFLRQAFGDDWGSILSFENREPVGSGCVAQVYKAYANTAFLETDSVQRLGRASCLPP
  FSHTGAVGGLRELFGYLGNGRKPPENLADQSFLERLLLPKADLVGSNAGVSRAQVPGHQP
  EATNLISVAVKVLHPGLLAQVHMDLLLMKIGSRVLGVLPGIKWLSLPEIVEEFEKLMVQQ
  IDLRYEAQNLEHFQVNFRNVKAVKFPTPLRPFVTREVLVETYEESVPVSSYQQAGIPVDL
  KRKIARLGINMLLKMIFVDNFVHADLHPGNILVQGANGLSSSQEAQLQQADICDTLVVAV
  PSSLCPLRLVLLDAGIVAELQAPDLRNFRAVFMAVVMGQGQRVAELILHHARASECRDVE
  GFKTEMAMLVTQARKNTITLEKLHVSSLLSSVFKLLMTHKVKLESNFASIVFAIMVLEGL
  GRSLDPKLDILEAARPFLLTGPVCPP
• Function: The function of this protein is not yet clear. It is not known if it has protein kinase activity and what type of substrate it would phosphorylate (Ser, Thr or Tyr) (Probable). Involved in the mitochondrial import of CoQ precursors, plays a role in muscle mitochondrial function and fatty acid beta-oxidation.

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Mitochondrial myopathy	DIS9SA7V	moderate	Biomarker	[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 Uncharacterized aarF domain-containing protein kinase 2 (ADCK2).	[2]
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of Uncharacterized aarF domain-containing protein kinase 2 (ADCK2).	[6]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Uncharacterized aarF domain-containing protein kinase 2 (ADCK2).	[8]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Uncharacterized aarF domain-containing protein kinase 2 (ADCK2).	[3]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Uncharacterized aarF domain-containing protein kinase 2 (ADCK2).	[4]
Cisplatin	DMRHGI9	Approved	Cisplatin affects the expression of Uncharacterized aarF domain-containing protein kinase 2 (ADCK2).	[5]
Decitabine	DMQL8XJ	Approved	Decitabine affects the expression of Uncharacterized aarF domain-containing protein kinase 2 (ADCK2).	[5]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Uncharacterized aarF domain-containing protein kinase 2 (ADCK2).	[7]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Uncharacterized aarF domain-containing protein kinase 2 (ADCK2).	[9]

References

• [1] ADCK2 Haploinsufficiency Reduces Mitochondrial Lipid Oxidation and Causes Myopathy Associated with CoQ Deficiency.J Clin Med. 2019 Sep 2;8(9):1374. doi: 10.3390/jcm8091374.
• [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] Blood transcript immune signatures distinguish a subset of people with elevated serum ALT from others given acetaminophen. Clin Pharmacol Ther. 2016 Apr;99(4):432-41.
• [4] 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.
• [5] Acute hypersensitivity of pluripotent testicular cancer-derived embryonal carcinoma to low-dose 5-aza deoxycytidine is associated with global DNA Damage-associated p53 activation, anti-pluripotency and DNA demethylation. PLoS One. 2012;7(12):e53003. doi: 10.1371/journal.pone.0053003. Epub 2012 Dec 27.
• [6] 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.
• [7] Definition of transcriptome-based indices for quantitative characterization of chemically disturbed stem cell development: introduction of the STOP-Toxukn and STOP-Toxukk tests. Arch Toxicol. 2017 Feb;91(2):839-864.
• [8] 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.
• [9] 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.