Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTNC58MD)

• DOT Name: Coiled-coil domain-containing protein 25 (CCDC25)
• Gene Name: CCDC25
• Related Disease:
  Cholangiocarcinoma
  Congenital contractural arachnodactyly
  Schizophrenia
• UniProt ID: CCD25_HUMAN
• PDB ID: 7EOE; 7EOF
• Pfam ID: PF05670
• Sequence:
  MVFYFTSSSVNSSAYTIYMGKDKYENEDLIKHGWPEDIWFHVDKLSSAHVYLRLHKGENI
  EDIPKEVLMDCAHLVKANSIQGCKMNNVNVVYTPWSNLKKTADMDVGQIGFHRQKDVKIV
  TVEKKVNEILNRLEKTKVERFPDLAAEKECRDREERNEKKAQIQEMKKREKEEMKKKREM
  DELRSYSSLMKVENMSSNQDGNDSDEFM
• Function: Transmembrane receptor that senses neutrophil extracellular traps (NETs) and triggers the ILK-PARVB pathway to enhance cell motility. NETs are mainly composed of DNA fibers and are released by neutrophils to bind pathogens during inflammation. Formation of NETs is also associated with cancer metastasis, NET-DNA acting as a chemotactic factor to attract cancer cells. Specifically binds NETs on its extracellular region, in particular the 8-OHdG-enriched DNA present in NETs, and recruits ILK, initiating the ILK-PARVB cascade to induce cytoskeleton rearrangement and directional migration of cells. In the context of cancer, promotes cancer metastasis by sensing NETs and promoting migration of tumor cells.

Molecular Interaction Atlas (MIA) of This DOT

3 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Cholangiocarcinoma	DIS71F6X	Strong	Altered Expression	[1]
Congenital contractural arachnodactyly	DISOM1K7	Strong	Biomarker	[1]
Schizophrenia	DISSRV2N	Strong	Altered Expression	[2]

This DOT Affected the Drug Response of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
NAPQI	DM8F5LR	Investigative	Coiled-coil domain-containing protein 25 (CCDC25) affects the response to substance of NAPQI.	[12]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the expression of Coiled-coil domain-containing protein 25 (CCDC25).	[3]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Coiled-coil domain-containing protein 25 (CCDC25).	[4]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Coiled-coil domain-containing protein 25 (CCDC25).	[5]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Coiled-coil domain-containing protein 25 (CCDC25).	[6]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Coiled-coil domain-containing protein 25 (CCDC25).	[8]
Genistein	DM0JETC	Phase 2/3	Genistein increases the expression of Coiled-coil domain-containing protein 25 (CCDC25).	[9]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Coiled-coil domain-containing protein 25 (CCDC25).	[11]

2 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 25 (CCDC25).	[7]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene affects the methylation of Coiled-coil domain-containing protein 25 (CCDC25).	[10]

References

• [1] High expression of CCDC25 in cholangiocarcinoma tissue samples.Oncol Lett. 2017 Aug;14(2):2566-2572. doi: 10.3892/ol.2017.6446. Epub 2017 Jun 21.
• [2] Genome-wide investigation of schizophrenia associated plasma Ndel1 enzyme activity.Schizophr Res. 2016 Apr;172(1-3):60-7. doi: 10.1016/j.schres.2016.01.043. Epub 2016 Feb 2.
• [3] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [4] 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.
• [5] 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.
• [6] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [7] 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.
• [8] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [9] Quantitative proteomics and transcriptomics addressing the estrogen receptor subtype-mediated effects in T47D breast cancer cells exposed to the phytoestrogen genistein. Mol Cell Proteomics. 2011 Jan;10(1):M110.002170.
• [10] 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.
• [11] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.
• [12] Acetaminophen-NAPQI hepatotoxicity: a cell line model system genome-wide association study. Toxicol Sci. 2011 Mar;120(1):33-41. doi: 10.1093/toxsci/kfq375. Epub 2010 Dec 22.