Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT1AOJCS)

• DOT Name: Coiled-coil domain-containing protein 85C (CCDC85C)
• Gene Name: CCDC85C
• Related Disease:
  Advanced cancer
  Hydrocephalus
  Neoplasm
  Subcortical band heterotopia
• UniProt ID: CC85C_HUMAN
• Pfam ID: PF10226
• Sequence:
  MAKPAATAAAASEELSQVPDEELLRWSKEELARRLRRAEGEKVGLMLEHGGLMRDVNRRL
  QQHLLEIRGLKDVNQRLQDDNQELRELCCFLDDDRQKGRKLAREWQRFGRHAAGAVWHEV
  ARSQQKLRELEARQEALLRENLELKELVLLLDEERAALAATGAASGGGGGGGGAGSRSSI
  DSQASLSGPLSGGAPGAGARDVGDGSSTSSAGSGGSPDHHHHVPPPLLPPGPHKAPDGKA
  GATRRSLDDLSAPPHHRSIPNGLHDPSSTYIRQLESKVRLLEGDKLLAQQAGSGEFRTLR
  KGFSPYHSESQLASLPPSYQDSLQNGPACPAPELPSPPSAGYSPAGQKPEAVVHAMKVLE
  VHENLDRQLQDSCEEDLSEKEKAIVREMCNVVWRKLGDAASSKPSIRQHLSGNQFKGPL
• Function: May play a role in cell-cell adhesion and epithelium development through its interaction with proteins of the beta-catenin family (Probable). May play an important role in cortical development, especially in the maintenance of radial glia.

Molecular Interaction Atlas (MIA) of This DOT

4 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Advanced cancer	DISAT1Z9	Strong	Altered Expression	[1]
Hydrocephalus	DISIZUF7	Strong	Biomarker	[2]
Neoplasm	DISZKGEW	Strong	Altered Expression	[1]
Subcortical band heterotopia	DISHN7JS	Strong	Biomarker	[1]

4 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 Coiled-coil domain-containing protein 85C (CCDC85C).	[3]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Coiled-coil domain-containing protein 85C (CCDC85C).	[4]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Coiled-coil domain-containing protein 85C (CCDC85C).	[5]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Coiled-coil domain-containing protein 85C (CCDC85C).	[7]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of Coiled-coil domain-containing protein 85C (CCDC85C).	[6]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 decreases the phosphorylation of Coiled-coil domain-containing protein 85C (CCDC85C).	[8]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Coiled-coil domain-containing protein 85C (CCDC85C).	[9]

References

• [1] Expression of Ccdc85C, a causative protein for murine hydrocephalus, in the mammary gland tumors of dogs.Histol Histopathol. 2017 Apr;32(4):397-403. doi: 10.14670/HH-11-806. Epub 2016 Jul 26.
• [2] Pathological characteristics of Ccdc85c knockout rats: a rat model of genetic hydrocephalus.Exp Anim. 2020 Jan 29;69(1):26-33. doi: 10.1538/expanim.19-0005. Epub 2019 Jul 23.
• [3] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [4] 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.
• [5] 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.
• [6] Prenatal arsenic exposure and the epigenome: identifying sites of 5-methylcytosine alterations that predict functional changes in gene expression in newborn cord blood and subsequent birth outcomes. Toxicol Sci. 2015 Jan;143(1):97-106. doi: 10.1093/toxsci/kfu210. Epub 2014 Oct 10.
• [7] New insights into BaP-induced toxicity: role of major metabolites in transcriptomics and contribution to hepatocarcinogenesis. Arch Toxicol. 2016 Jun;90(6):1449-58.
• [8] Quantitative phosphoproteomics reveal cellular responses from caffeine, coumarin and quercetin in treated HepG2 cells. Toxicol Appl Pharmacol. 2022 Aug 15;449:116110. doi: 10.1016/j.taap.2022.116110. Epub 2022 Jun 7.
• [9] 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.