Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTTD4AY0)

• DOT Name: Actin-related protein 6 (ACTR6)
• Synonyms: hArp6; hARPX
• Gene Name: ACTR6
• UniProt ID: ARP6_HUMAN
• PDB ID: 6IGM
• Pfam ID: PF00022
• Sequence:
  MTTLVLDNGAYNAKIGYSHENVSVIPNCQFRSKTARLKTFTANQIDEIKDPSGLFYILPF
  QKGYLVNWDVQRQVWDYLFGKEMYQVDFLDTNIIITEPYFNFTSIQESMNEILFEEYQFQ
  AVLRVNAGALSAHRYFRDNPSELCCIIVDSGYSFTHIVPYCRSKKKKEAIIRINVGGKLL
  TNHLKEIISYRQLHVMDETHVINQVKEDVCYVSQDFYRDMDIAKLKGEENTVMIDYVLPD
  FSTIKKGFCKPREEMVLSGKYKSGEQILRLANERFAVPEILFNPSDIGIQEMGIPEAIVY
  SIQNLPEEMQPHFFKNIVLTGGNSLFPGFRDRVYSEVRCLTPTDYDVSVVLPENPITYAW
  EGGKLISENDDFEDMVVTREDYEENGHSVCEEKFDI
• Function: Required for formation and/or maintenance of proper nucleolar structure and function. Plays a dual role in the regulation of ribosomal DNA (rDNA) transcription. In the presence of high glucose, maintains active rDNA transcription through H2A.Z deposition and under glucose starvation, is required for the repression of rDNA transcription, and this function may be independent of H2A.Z.
• KEGG Pathway: ATP-dependent chromatin remodeling (hsa03082)

Molecular Interaction Atlas (MIA) of This DOT

7 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 Actin-related protein 6 (ACTR6).	[1]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Actin-related protein 6 (ACTR6).	[2]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Actin-related protein 6 (ACTR6).	[3]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Actin-related protein 6 (ACTR6).	[4]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of Actin-related protein 6 (ACTR6).	[5]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of Actin-related protein 6 (ACTR6).	[6]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Actin-related protein 6 (ACTR6).	[8]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Actin-related protein 6 (ACTR6).	[7]

References

• [1] A genomic approach to predict synergistic combinations for breast cancer treatment. Pharmacogenomics J. 2013 Feb;13(1):94-104. doi: 10.1038/tpj.2011.48. Epub 2011 Nov 15.
• [2] 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.
• [3] 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.
• [4] 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.
• [5] Temozolomide induces activation of Wnt/-catenin signaling in glioma cells via PI3K/Akt pathway: implications in glioma therapy. Cell Biol Toxicol. 2020 Jun;36(3):273-278. doi: 10.1007/s10565-019-09502-7. Epub 2019 Nov 22.
• [6] 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.
• [7] 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.
• [8] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.