Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTS6N7I6)

• DOT Name: Coiled-coil domain-containing protein 178 (CCDC178)
• Gene Name: CCDC178
• Related Disease:
  Advanced cancer
  Hepatocellular carcinoma
• UniProt ID: CC178_HUMAN
• Sequence:
  MTENKTVSSSSTRDDQTNIGLTCQEVKALREKAWSRTNEGNAMSQSLVLYGASKENSEGF
  HESKMTNTEGVNKGIYFSYPCRRHSCAVVNIPAPCVNKMISHIQDVESKIQEHLKRFETS
  FEEWSRTSSTKDLKEDWSVTTPVKEVKPGEKRDEKCPELKQEMETLLSEAIRLIKSLETD
  RADAEEALKQQRSRKNMINMKIDSWSVWKLQELPLAVQKEHEAYLSDVIELQWHLEDKAN
  QLQHFEKQKTELEEANAKIQADIDYMNEHGPLLDSKQNQELQDLKNHYKKKMEVMDLHRK
  VNEELEEALEACENARLKAQQIKEEIDKDIYQDEKTIEAYKREIYQLNSLFDHYSSSVIN
  VNTNIEEKEEEVTEAIRETKSSKNELHSLSKMLEDLRRVYDQLTWKQKSHENQYLEAVND
  FYAAKKTWDIELSDVAKDFSAISLACTKLTEDNKKLEIDINKITVKTNESIRKKSKYESE
  IKYLTIMKLKNDKHLKNIYKEAYRIGTLFHLTKHKTDEMEDKIAEVRRKFKGREEFLKKL
  TQGEVAAGMVLQKKLYSIYEVQALERKELIKNRAICAMSLAELQEPLLQLEDEAERIRSL
  DKEHSVMLNNIIDQKDLIRRKVGKVKKKLRKKGKKTLDALIETESKRSAIFKDLEATKSK
  TMIFYAKINELNEELKAKEEEKKSFDQTLEILKNKFITMRFKREHAQTVFDHYMQEKKDC
  EERIFEEDQRFRVLLAVRQKTLQDTQKIIADSLEENLRLAQEYQQLQITFLKEKDNYFNI
  YDKQLSLDTSIRDKKQLCQLQRRMHTLWQEHFKLVVLFSQMRLANFQTDSQESIQKILAV
  QEESSNLMQHILGFFQTLTDGTCENDG

Molecular Interaction Atlas (MIA) of This DOT

2 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Advanced cancer	DISAT1Z9	moderate	Biomarker	[1]
Hepatocellular carcinoma	DIS0J828	moderate	Biomarker	[1]

2 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 178 (CCDC178).	[2]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Coiled-coil domain-containing protein 178 (CCDC178).	[3]

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 178 (CCDC178).	[4]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Coiled-coil domain-containing protein 178 (CCDC178).	[5]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A affects the methylation of Coiled-coil domain-containing protein 178 (CCDC178).	[6]

References

• [1] CCDC178 promotes hepatocellular carcinoma metastasis through modulation of anoikis.Oncogene. 2017 Jul 13;36(28):4047-4059. doi: 10.1038/onc.2017.10. Epub 2017 Mar 20.
• [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] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [4] 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.
• [5] 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.
• [6] 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.