Details of Drug Off-Target (DOT)

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

• DOT Name: DnaJ homolog subfamily C member 9 (DNAJC9)
• Synonyms: HDJC9; DnaJ protein SB73
• Gene Name: DNAJC9
• Related Disease: Epithelial recurrent erosion dystrophy
• UniProt ID: DNJC9_HUMAN
• PDB ID: 7CIZ; 7CJ0
• Pfam ID: PF00226
• Sequence:
  MGLLDLCEEVFGTADLYRVLGVRREASDGEVRRGYHKVSLQVHPDRVGEGDKEDATRRFQ
  ILGKVYSVLSDREQRAVYDEQGTVDEDSPVLTQDRDWEAYWRLLFKKISLEDIQAFEKTY
  KGSEEELADIKQAYLDFKGDMDQIMESVLCVQYTEEPRIRNIIQQAIDAGEVPSYNAFVK
  ESKQKMNARKRRAQEEAKEAEMSRKELGLDEGVDSLKAAIQSRQKDRQKEMDNFLAQMEA
  KYCKSSKGGGKKSALKKEKK
• Function: Acts as a dual histone chaperone and heat shock co-chaperone. As a histone chaperone, forms a co-chaperone complex with MCM2 and histone H3-H4 heterodimers; and may thereby assist MCM2 in histone H3-H4 heterodimer recognition and facilitate the assembly of histones into nucleosomes. May also act as a histone co-chaperone together with TONSL. May recruit histone chaperones ASF1A, NASP and SPT2 to histone H3-H4 heterodimers. Also plays a role as co-chaperone of the HSP70 family of molecular chaperone proteins, such as HSPA1A, HSPA1B and HSPA8. As a co-chaperone, may play a role in the recruitment of HSP70-type molecular chaperone machinery to histone H3-H4 substrates, thereby maintaining the histone structural integrity. Exhibits activity to assemble histones onto DNA in vitro.
• Tissue Specificity: Expressed in heart, placenta, liver, skeletal muscle, kidney, pancreas, thymus, ovary, colon and peripheral blood.

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Epithelial recurrent erosion dystrophy	DIS2XPWB	Strong	Biomarker	[1]

18 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 9 (DNAJC9).	[2]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of DnaJ homolog subfamily C member 9 (DNAJC9).	[3]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of DnaJ homolog subfamily C member 9 (DNAJC9).	[4]
Doxorubicin	DMVP5YE	Approved	Doxorubicin increases the expression of DnaJ homolog subfamily C member 9 (DNAJC9).	[5]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of DnaJ homolog subfamily C member 9 (DNAJC9).	[6]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of DnaJ homolog subfamily C member 9 (DNAJC9).	[7]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide increases the expression of DnaJ homolog subfamily C member 9 (DNAJC9).	[8]
Calcitriol	DM8ZVJ7	Approved	Calcitriol decreases the expression of DnaJ homolog subfamily C member 9 (DNAJC9).	[9]
Testosterone	DM7HUNW	Approved	Testosterone decreases the expression of DnaJ homolog subfamily C member 9 (DNAJC9).	[9]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of DnaJ homolog subfamily C member 9 (DNAJC9).	[10]
Selenium	DM25CGV	Approved	Selenium decreases the expression of DnaJ homolog subfamily C member 9 (DNAJC9).	[11]
Niclosamide	DMJAGXQ	Approved	Niclosamide decreases the expression of DnaJ homolog subfamily C member 9 (DNAJC9).	[12]
Diclofenac	DMPIHLS	Approved	Diclofenac affects the expression of DnaJ homolog subfamily C member 9 (DNAJC9).	[10]
Piroxicam	DMTK234	Approved	Piroxicam increases the expression of DnaJ homolog subfamily C member 9 (DNAJC9).	[13]
Atazanavir	DMSYRBX	Approved	Atazanavir increases the expression of DnaJ homolog subfamily C member 9 (DNAJC9).	[3]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of DnaJ homolog subfamily C member 9 (DNAJC9).	[14]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of DnaJ homolog subfamily C member 9 (DNAJC9).	[15]
Coumestrol	DM40TBU	Investigative	Coumestrol increases the expression of DnaJ homolog subfamily C member 9 (DNAJC9).	[17]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Coumarin	DM0N8ZM	Investigative	Coumarin increases the phosphorylation of DnaJ homolog subfamily C member 9 (DNAJC9).	[16]

References

• [1] A COL17A1 Splice-Altering Mutation Is Prevalent in Inherited Recurrent Corneal Erosions. Ophthalmology. 2016 Apr;123(4):709-22. doi: 10.1016/j.ophtha.2015.12.008. Epub 2016 Jan 16.
• [2] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [3] Robustness testing and optimization of an adverse outcome pathway on cholestatic liver injury. Arch Toxicol. 2020 Apr;94(4):1151-1172. doi: 10.1007/s00204-020-02691-9. Epub 2020 Mar 10.
• [4] Predictive toxicology using systemic biology and liver microfluidic "on chip" approaches: application to acetaminophen injury. Toxicol Appl Pharmacol. 2012 Mar 15;259(3):270-80.
• [5] 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.
• [6] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [7] 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.
• [8] Arsenic suppresses gene expression in promyelocytic leukemia cells partly through Sp1 oxidation. Blood. 2005 Jul 1;106(1):304-10.
• [9] Effects of 1alpha,25 dihydroxyvitamin D3 and testosterone on miRNA and mRNA expression in LNCaP cells. Mol Cancer. 2011 May 18;10:58.
• [10] 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.
• [11] Selenium and vitamin E: cell type- and intervention-specific tissue effects in prostate cancer. J Natl Cancer Inst. 2009 Mar 4;101(5):306-20.
• [12] Mitochondrial Uncoupling Induces Epigenome Remodeling and Promotes Differentiation in Neuroblastoma. Cancer Res. 2023 Jan 18;83(2):181-194. doi: 10.1158/0008-5472.CAN-22-1029.
• [13] Apoptosis induced by piroxicam plus cisplatin combined treatment is triggered by p21 in mesothelioma. PLoS One. 2011;6(8):e23569.
• [14] Identification of a transcriptomic signature of food-relevant genotoxins in human HepaRG hepatocarcinoma cells. Food Chem Toxicol. 2020 Jun;140:111297. doi: 10.1016/j.fct.2020.111297. Epub 2020 Mar 28.
• [15] 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.
• [16] 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.
• [17] Pleiotropic combinatorial transcriptomes of human breast cancer cells exposed to mixtures of dietary phytoestrogens. Food Chem Toxicol. 2009 Apr;47(4):787-95.