Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT16EAZ7)

• DOT Name: Coiled-coil domain-containing protein 82 (CCDC82)
• Gene Name: CCDC82
• Related Disease: Parkinson disease
• UniProt ID: CCD82_HUMAN
• Pfam ID: PF13846 ; PF13926
• Sequence:
  MIHVRRHETRRNSKSHVPEQKSRVDWRRTKRSSISQLLDSDEELDSEEFDSDEELDSDES
  FENDEELDSNKGPDCNKTPGSERELNLSKIQSEGNDSKCLINSGNGSTYEEETNKIKHRN
  IDLQDQEKHLSQEDNDLNKQTGQIIEDDQEKHLSQEDNDLNKQTGQIIEDDLEEEDIKRG
  KRKRLSSVMCDSDESDDSDILVRKVGVKRPRRVVEDEGSSVEMEQKTPEKTLAAQKREKL
  QKLKELSKQRSRQRRSSGRDFEDSEKESCPSSDEVDEEEEEDNYESDEDGDDYIIDDFVV
  QDEEGDEENKNQQGEKLTTSQLKLVKQNSLYSFSDHYTHFERVVKALLINALDESFLGTL
  YDGTRQKSYAKDMLTSLHYLDNRFVQPRLESLVSRSRWKEQYKERVENYSNVSIHLKNPE
  NCSCQACGLHRYCKYSVHLSGELYNTRTMQIDNFMSHDKQVFTVGRICASRTRIYHKLKH
  FKFKLYQECCTIAMTEEVEDEQVKETVERIFRRSKENGWIKEKYGQLEEYLNFADYFQEE
  KFEL

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Parkinson disease	DISQVHKL	Strong	Genetic Variation	[1]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the methylation of Coiled-coil domain-containing protein 82 (CCDC82).	[2]
TAK-243	DM4GKV2	Phase 1	TAK-243 increases the sumoylation of Coiled-coil domain-containing protein 82 (CCDC82).	[9]

11 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 Coiled-coil domain-containing protein 82 (CCDC82).	[3]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Coiled-coil domain-containing protein 82 (CCDC82).	[4]
Vorinostat	DMWMPD4	Approved	Vorinostat increases the expression of Coiled-coil domain-containing protein 82 (CCDC82).	[5]
Methotrexate	DM2TEOL	Approved	Methotrexate increases the expression of Coiled-coil domain-containing protein 82 (CCDC82).	[6]
Demecolcine	DMCZQGK	Approved	Demecolcine increases the expression of Coiled-coil domain-containing protein 82 (CCDC82).	[7]
Bortezomib	DMNO38U	Approved	Bortezomib increases the expression of Coiled-coil domain-containing protein 82 (CCDC82).	[8]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Coiled-coil domain-containing protein 82 (CCDC82).	[10]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Coiled-coil domain-containing protein 82 (CCDC82).	[11]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Coiled-coil domain-containing protein 82 (CCDC82).	[12]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of Coiled-coil domain-containing protein 82 (CCDC82).	[7]
methyl p-hydroxybenzoate	DMO58UW	Investigative	methyl p-hydroxybenzoate decreases the expression of Coiled-coil domain-containing protein 82 (CCDC82).	[13]

References

• [1] Parkinson disease loci in the mid-western Amish.Hum Genet. 2013 Nov;132(11):1213-21. doi: 10.1007/s00439-013-1316-1. Epub 2013 Jun 21.
• [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] 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.
• [4] 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.
• [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] The contribution of methotrexate exposure and host factors on transcriptional variance in human liver. Toxicol Sci. 2007 Jun;97(2):582-94.
• [7] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
• [8] The proapoptotic effect of zoledronic acid is independent of either the bone microenvironment or the intrinsic resistance to bortezomib of myeloma cells and is enhanced by the combination with arsenic trioxide. Exp Hematol. 2011 Jan;39(1):55-65.
• [9] Inhibiting ubiquitination causes an accumulation of SUMOylated newly synthesized nuclear proteins at PML bodies. J Biol Chem. 2019 Oct 18;294(42):15218-15234. doi: 10.1074/jbc.RA119.009147. Epub 2019 Jul 8.
• [10] Cell-based two-dimensional morphological assessment system to predict cancer drug-induced cardiotoxicity using human induced pluripotent stem cell-derived cardiomyocytes. Toxicol Appl Pharmacol. 2019 Nov 15;383:114761. doi: 10.1016/j.taap.2019.114761. Epub 2019 Sep 15.
• [11] Bisphenol A induces DSB-ATM-p53 signaling leading to cell cycle arrest, senescence, autophagy, stress response, and estrogen release in human fetal lung fibroblasts. Arch Toxicol. 2018 Apr;92(4):1453-1469.
• [12] 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.
• [13] Transcriptome dynamics of alternative splicing events revealed early phase of apoptosis induced by methylparaben in H1299 human lung carcinoma cells. Arch Toxicol. 2020 Jan;94(1):127-140. doi: 10.1007/s00204-019-02629-w. Epub 2019 Nov 20.