Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTO9ZBI5)

• DOT Name: Dual specificity tyrosine-phosphorylation-regulated kinase 4 (DYRK4)
• Synonyms: EC 2.7.12.1
• Gene Name: DYRK4
• UniProt ID: DYRK4_HUMAN
• EC Number: 2.7.12.1
• Pfam ID: PF00069
• Sequence:
  MPASELKASEIPFHPSIKTQDPKAEEKSPKKQKVTLTAAEALKLFKNQLSPYEQSEILGY
  AELWFLGLEAKKLDTAPEKFSKTSFDDEHGFYLKVLHDHIAYRYEVLETIGKGSFGQVAK
  CLDHKNNELVALKIIRNKKRFHQQALMELKILEALRKKDKDNTYNVVHMKDFFYFRNHFC
  ITFELLGINLYELMKNNNFQGFSLSIVRRFTLSVLKCLQMLSVEKIIHCDLKPENIVLYQ
  KGQASVKVIDFGSSCYEHQKVYTYIQSRFYRSPEVILGHPYDVAIDMWSLGCITAELYTG
  YPLFPGENEVEQLACIMEVLGLPPAGFIQTASRRQTFFDSKGFPKNITNNRGKKRYPDSK
  DLTMVLKTYDTSFLDFLRRCLVWEPSLRMTPDQALKHAWIHQSRNLKPQPRPQTLRKSNS
  FFPSETRKDKVQGCHHSSRKADEITKETTEKTKDSPTKHVQHSGDQQDCLQHGADTVQLP
  QLVDAPKKSEAAVGAEVSMTSPGQSKNFSLKNTNVLPPIV
• Function: Possible non-essential role in spermiogenesis.

Molecular Interaction Atlas (MIA) of This DOT

2 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 Dual specificity tyrosine-phosphorylation-regulated kinase 4 (DYRK4).	[1]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Dual specificity tyrosine-phosphorylation-regulated kinase 4 (DYRK4).	[6]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Dual specificity tyrosine-phosphorylation-regulated kinase 4 (DYRK4).	[2]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Dual specificity tyrosine-phosphorylation-regulated kinase 4 (DYRK4).	[3]
Estradiol	DMUNTE3	Approved	Estradiol affects the expression of Dual specificity tyrosine-phosphorylation-regulated kinase 4 (DYRK4).	[4]
Vorinostat	DMWMPD4	Approved	Vorinostat increases the expression of Dual specificity tyrosine-phosphorylation-regulated kinase 4 (DYRK4).	[5]
THAPSIGARGIN	DMDMQIE	Preclinical	THAPSIGARGIN increases the expression of Dual specificity tyrosine-phosphorylation-regulated kinase 4 (DYRK4).	[7]

References

• [1] 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.
• [2] Comparison of HepG2 and HepaRG by whole-genome gene expression analysis for the purpose of chemical hazard identification. Toxicol Sci. 2010 May;115(1):66-79.
• [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] Identification of novel low-dose bisphenol a targets in human foreskin fibroblast cells derived from hypospadias patients. PLoS One. 2012;7(5):e36711. doi: 10.1371/journal.pone.0036711. Epub 2012 May 4.
• [5] 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.
• [6] 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.
• [7] Endoplasmic reticulum stress impairs insulin signaling through mitochondrial damage in SH-SY5Y cells. Neurosignals. 2012;20(4):265-80.