Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT2UF6YM)

• DOT Name: Adenylate kinase 8 (AK8)
• Synonyms: AK 8; EC 2.7.4.3; EC 2.7.4.6; ATP-AMP transphosphorylase 8
• Gene Name: AK8
• Related Disease:
  Attention deficit hyperactivity disorder
  Hydrocephalus
• UniProt ID: KAD8_HUMAN
• EC Number: 2.7.4.3; 2.7.4.6
• Pfam ID: PF00406
• Sequence:
  MDATIAPHRIPPEMPQYGEENHIFELMQNMLEQLLIHQPEDPIPFMIQHLHRDNDNVPRI
  VILGPPASGKTTIAMWLCKHLNSSLLTLENLILNEFSYTATEARRLYLQRKTVPSALLVQ
  LIQERLAEEDCIKQGWILDGIPETREQALRIQTLGITPRHVIVLSAPDTVLIERNLGKRI
  DPQTGEIYHTTFDWPPESEIQNRLMVPEDISELETAQKLLEYHRNIVRVIPSYPKILKVI
  SADQPCVDVFYQALTYVQSNHRTNAPFTPRVLLLGPVGSGKSLQAALLAQKYRLVNVCCG
  QLLKEAVADRTTFGELIQPFFEKEMAVPDSLLMKVLSQRLDQQDCIQKGWVLHGVPRDLD
  QAHLLNRLGYNPNRVFFLNVPFDSIMERLTLRRIDPVTGERYHLMYKPPPTMEIQARLLQ
  NPKDAEEQVKLKMDLFYRNSADLEQLYGSAITLNGDQDPYTVFEYIESGIINPLPKKIP
• Function: Nucleoside monophosphate (NMP) kinase that catalyzes the reversible transfer of the terminal phosphate group between nucleoside triphosphates and monophosphates. Has highest activity toward AMP, and weaker activity toward dAMP, CMP and dCMP. Also displays broad nucleoside diphosphate kinase activity.
• Tissue Specificity: Expressed in respiratory cells (at protein level).
• KEGG Pathway:
  Purine metabolism (hsa00230)
  Thiamine metabolism (hsa00730)
  Metabolic pathways (hsa01100)
  Nucleotide metabolism (hsa01232)
  Biosynthesis of cofactors (hsa01240)
• Reactome Pathway: Interconversion of nucleotide di- and triphosphates (R-HSA-499943)

Molecular Interaction Atlas (MIA) of This DOT

2 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Attention deficit hyperactivity disorder	DISL8MX9	Strong	Genetic Variation	[1]
Hydrocephalus	DISIZUF7	Strong	Biomarker	[2]

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 Adenylate kinase 8 (AK8).	[3]
Fulvestrant	DM0YZC6	Approved	Fulvestrant decreases the methylation of Adenylate kinase 8 (AK8).	[5]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Adenylate kinase 8 (AK8).	[5]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Adenylate kinase 8 (AK8).	[4]
Sodium lauryl sulfate	DMLJ634	Approved	Sodium lauryl sulfate increases the expression of Adenylate kinase 8 (AK8).	[6]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Adenylate kinase 8 (AK8).	[7]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A affects the expression of Adenylate kinase 8 (AK8).	[8]

References

• [1] Molecular genetics of adult ADHD: converging evidence from genome-wide association and extended pedigree linkage studies.J Neural Transm (Vienna). 2008 Nov;115(11):1573-85. doi: 10.1007/s00702-008-0119-3. Epub 2008 Oct 7.
• [2] Congenital hydrocephalus in genetically engineered mice.Vet Pathol. 2012 Jan;49(1):166-81. doi: 10.1177/0300985811415708. Epub 2011 Jul 11.
• [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] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [5] DNA methylome-wide alterations associated with estrogen receptor-dependent effects of bisphenols in breast cancer. Clin Epigenetics. 2019 Oct 10;11(1):138. doi: 10.1186/s13148-019-0725-y.
• [6] CXCL14 downregulation in human keratinocytes is a potential biomarker for a novel in vitro skin sensitization test. Toxicol Appl Pharmacol. 2020 Jan 1;386:114828. doi: 10.1016/j.taap.2019.114828. Epub 2019 Nov 14.
• [7] Identification of a transcriptomic signature of food-relevant genotoxins in human HepaRG hepatocarcinoma cells. Food Chem Toxicol. 2020 Jun;140:111297. doi: 10.1016/j.fct.2020.111297. Epub 2020 Mar 28.
• [8] A trichostatin A expression signature identified by TempO-Seq targeted whole transcriptome profiling. PLoS One. 2017 May 25;12(5):e0178302. doi: 10.1371/journal.pone.0178302. eCollection 2017.