Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTB7NSK3)

• DOT Name: AarF domain-containing protein kinase 1 (ADCK1)
• Synonyms: EC 2.7.-.-
• Gene Name: ADCK1
• Related Disease:
  Obsessive compulsive disorder
  Autosomal dominant optic atrophy, classic form
  Schizophrenia
• UniProt ID: ADCK1_HUMAN
• EC Number: 2.7.-.-
• Pfam ID: PF03109
• Sequence:
  MARKALKLASWTSMALAASGIYFYSNKYLDPNDFGAVRVGRAVATTAVISYDYLTSLKSV
  PYGSEEYLQLRSKSWPVFLQVHLRSARRLCELCCANRGTFIKVGQHLGALDYLLPEEYTS
  TLKVLHSQAPQSSMQEIRQVIREDLGKEIHDLFQSFDDTPLGTASLAQVHKAVLHDGRTV
  AVKVQHPKVRAQSSKDILLMEVLVLAVKQLFPEFEFMWLVDEAKKNLPLELDFLNEGRNA
  EKVSQMLRHFDFLKVPRIHWDLSTERVLLMEFVDGGQVNDRDYMERNKIDVNEISRHLGK
  MYSEMIFVNGFVHCDPHPGNVLVRKHPGTGKAEIVLLDHGLYQMLTEEFRLNYCHLWQSL
  IWTDMKRVKEYSQRLGAGDLYPLFACMLTARSWDSVNRGISQAPVTATEDLEIRNNAANY
  LPQISHLLNHVPRQMLLILKTNDLLRGIEAALGTRASASSFLNMSRCCIRALAEHKKKNT
  CSFFRRTQISFSEAFNLWQINLHELILRVKGLKLADRVLALICWLFPAPL
• Function: Appears to be essential for maintaining mitochondrial cristae formation and mitochondrial function by acting via YME1L1 in a kinase-independent manner to regulate essential mitochondrial structural proteins OPA1 and IMMT. The action of this enzyme is not yet clear (Probable). It is not known if it has protein kinase activity and what type of substrate it would phosphorylate (Ser, Thr or Tyr) (Probable).

Molecular Interaction Atlas (MIA) of This DOT

3 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Obsessive compulsive disorder	DIS1ZMM2	Definitive	Genetic Variation	[1]
Autosomal dominant optic atrophy, classic form	DISXUAV9	Strong	Biomarker	[2]
Schizophrenia	DISSRV2N	Limited	Genetic Variation	[3]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the expression of AarF domain-containing protein kinase 1 (ADCK1).	[4]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of AarF domain-containing protein kinase 1 (ADCK1).	[5]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of AarF domain-containing protein kinase 1 (ADCK1).	[6]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of AarF domain-containing protein kinase 1 (ADCK1).	[7]

References

• [1] Sex differences in the genetic architecture of obsessive-compulsive disorder.Am J Med Genet B Neuropsychiatr Genet. 2019 Sep;180(6):351-364. doi: 10.1002/ajmg.b.32687. Epub 2018 Nov 20.
• [2] Drosophila ADCK1 is critical for maintaining mitochondrial structures and functions in the muscle.PLoS Genet. 2019 May 24;15(5):e1008184. doi: 10.1371/journal.pgen.1008184. eCollection 2019 May.
• [3] Genetic variations in the ADCK1 gene predict paliperidone palmitate efficacy in Han Chinese patients with schizophrenia.J Neural Transm (Vienna). 2019 Jan;126(1):19-25. doi: 10.1007/s00702-018-1953-6. Epub 2018 Nov 13.
• [4] 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.
• [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] 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.
• [7] 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.