Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTBE4I4X)

• DOT Name: DnaJ homolog subfamily C member 8 (DNAJC8)
• Synonyms: Splicing protein spf31
• Gene Name: DNAJC8
• Related Disease:
  Cervical cancer
  Cervical carcinoma
• UniProt ID: DNJC8_HUMAN
• PDB ID: 7VPX
• Pfam ID: PF00226
• Sequence:
  MAASGESGTSGGGGSTEEAFMTFYSEVKQIEKRDSVLTSKNQIERLTRPGSSYFNLNPFE
  VLQIDPEVTDEEIKKRFRQLSILVHPDKNQDDADRAQKAFEAVDKAYKLLLDQEQKKRAL
  DVIQAGKEYVEHTVKERKKQLKKEGKPTIVEEDDPELFKQAVYKQTMKLFAELEIKRKER
  EAKEMHERKRQREEEIEAQEKAKREREWQKNFEESRDGRVDSWRNFQANTKGKKEKKNRT
  FLRPPKVKMEQRE
• Function: Suppresses polyglutamine (polyQ) aggregation of ATXN3 in neuronal cells.
• Tissue Specificity: Ubiquitous.
• Reactome Pathway: mRNA Splicing - Major Pathway (R-HSA-72163)

Molecular Interaction Atlas (MIA) of This DOT

2 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Cervical cancer	DISFSHPF	Strong	Biomarker	[1]
Cervical carcinoma	DIST4S00	Strong	Biomarker	[1]

7 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 DnaJ homolog subfamily C member 8 (DNAJC8).	[2]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of DnaJ homolog subfamily C member 8 (DNAJC8).	[3]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of DnaJ homolog subfamily C member 8 (DNAJC8).	[4]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of DnaJ homolog subfamily C member 8 (DNAJC8).	[5]
Diethylstilbestrol	DMN3UXQ	Approved	Diethylstilbestrol decreases the expression of DnaJ homolog subfamily C member 8 (DNAJC8).	[6]
Diclofenac	DMPIHLS	Approved	Diclofenac affects the expression of DnaJ homolog subfamily C member 8 (DNAJC8).	[5]
chloropicrin	DMSGBQA	Investigative	chloropicrin increases the expression of DnaJ homolog subfamily C member 8 (DNAJC8).	[8]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
TAK-243	DM4GKV2	Phase 1	TAK-243 increases the sumoylation of DnaJ homolog subfamily C member 8 (DNAJC8).	[7]

References

• [1] Tazarotene-Induced Gene 1 Interacts with DNAJC8 and Regulates Glycolysis in Cervical Cancer Cells.Mol Cells. 2018 Jun;41(6):562-574. doi: 10.14348/molcells.2018.2347. Epub 2018 Jun 14.
• [2] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [3] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [4] 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.
• [5] Drug-induced endoplasmic reticulum and oxidative stress responses independently sensitize toward TNF-mediated hepatotoxicity. Toxicol Sci. 2014 Jul;140(1):144-59. doi: 10.1093/toxsci/kfu072. Epub 2014 Apr 20.
• [6] Identification of biomarkers and outcomes of endocrine disruption in human ovarian cortex using In Vitro Models. Toxicology. 2023 Feb;485:153425. doi: 10.1016/j.tox.2023.153425. Epub 2023 Jan 5.
• [7] 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.
• [8] Transcriptomic analysis of human primary bronchial epithelial cells after chloropicrin treatment. Chem Res Toxicol. 2015 Oct 19;28(10):1926-35.