Details of Drug Off-Target (DOT)

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

DOT Name	DnaJ homolog subfamily C member 15 (DNAJC15)
Synonyms	Cell growth-inhibiting gene 22 protein; Methylation-controlled J protein; MCJ
Gene Name	DNAJC15
Related Disease	Metabolic disorder ( ) Ovarian neoplasm ( ) Brain neoplasm ( ) Ependymoma ( ) Epithelial ovarian cancer ( ) Medulloblastoma ( ) Melanoma ( ) Neoplasm ( ) Ovarian cancer ( ) Primitive neuroectodermal tumor ( ) Breast cancer ( ) Breast carcinoma ( )
UniProt ID	DJC15_HUMAN
3D Structure	Download 2D Sequence (FASTA) Download 3D Structure (PDB) Download
Sequence	MAARGVIAPVGESLRYAEYLQPSAKRPDADVDQQRLVRSLIAVGLGVAALAFAGRYAFRI WKPLEQVITETAKKISTPSFSSYYKGGFEQKMSRREAGLILGVSPSAGKAKIRTAHRRVM ILNHPDKGGSPYVAAKINEAKDLLETTTKH
Function	Negative regulator of the mitochondrial respiratory chain. Prevents mitochondrial hyperpolarization state and restricts mitochondrial generation of ATP. Acts as an import component of the TIM23 translocase complex. Stimulates the ATPase activity of HSPA9.
Tissue Specificity	Expressed at highest levels in heart, followed by liver and kidney.

Molecular Interaction Atlas (MIA) of This DOT

12 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance
Metabolic disorder	DIS71G5H	Definitive	Altered Expression	[1]
Ovarian neoplasm	DISEAFTY	Definitive	Altered Expression	[2]
Brain neoplasm	DISY3EKS	Strong	Posttranslational Modification	[3]
Ependymoma	DISUMRNZ	Strong	Posttranslational Modification	[3]
Epithelial ovarian cancer	DIS56MH2	Strong	Genetic Variation	[4]
Medulloblastoma	DISZD2ZL	Strong	Posttranslational Modification	[3]
Melanoma	DIS1RRCY	Strong	Biomarker	[5]
Neoplasm	DISZKGEW	Strong	Biomarker	[3]
Ovarian cancer	DISZJHAP	Strong	Altered Expression	[2]
Primitive neuroectodermal tumor	DISFHXHA	Strong	Posttranslational Modification	[3]
Breast cancer	DIS7DPX1	Limited	Biomarker	[6]
Breast carcinoma	DIS2UE88	Limited	Biomarker	[6]
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Molecular Interaction Atlas (MIA)

MIA Detail

Jump to Detail Molecular Interaction Atlas of This DOT

11 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 15 (DNAJC15).	[7]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of DnaJ homolog subfamily C member 15 (DNAJC15).	[8]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of DnaJ homolog subfamily C member 15 (DNAJC15).	[9]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of DnaJ homolog subfamily C member 15 (DNAJC15).	[10]
Decitabine	DMQL8XJ	Approved	Decitabine affects the expression of DnaJ homolog subfamily C member 15 (DNAJC15).	[5]
Phenobarbital	DMXZOCG	Approved	Phenobarbital decreases the expression of DnaJ homolog subfamily C member 15 (DNAJC15).	[12]
Isotretinoin	DM4QTBN	Approved	Isotretinoin decreases the expression of DnaJ homolog subfamily C member 15 (DNAJC15).	[13]
Diclofenac	DMPIHLS	Approved	Diclofenac affects the expression of DnaJ homolog subfamily C member 15 (DNAJC15).	[10]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of DnaJ homolog subfamily C member 15 (DNAJC15).	[14]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of DnaJ homolog subfamily C member 15 (DNAJC15).	[15]
Deguelin	DMXT7WG	Investigative	Deguelin increases the expression of DnaJ homolog subfamily C member 15 (DNAJC15).	[17]
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⏷ Show the Full List of 11 Drug(s)

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of DnaJ homolog subfamily C member 15 (DNAJC15).	[16]
Hexadecanoic acid	DMWUXDZ	Investigative	Hexadecanoic acid increases the phosphorylation of DnaJ homolog subfamily C member 15 (DNAJC15).	[18]
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References

1	MCJ/DnaJC15, an endogenous mitochondrial repressor of the respiratory chain that controls metabolic alterations.Mol Cell Biol. 2013 Jun;33(11):2302-14. doi: 10.1128/MCB.00189-13. Epub 2013 Mar 25.
2	Cell type-specific methylation of an intronic CpG island controls expression of the MCJ gene.Carcinogenesis. 2004 May;25(5):693-701. doi: 10.1093/carcin/bgh066. Epub 2004 Jan 16.
3	Epigenetic inactivation of MCJ (DNAJD1) in malignant paediatric brain tumours.Int J Cancer. 2006 Jan 15;118(2):346-52. doi: 10.1002/ijc.21353.
4	Demethylation of the MCJ gene in stage III/IV epithelial ovarian cancer and response to chemotherapy.Gynecol Oncol. 2005 Jun;97(3):898-903. doi: 10.1016/j.ygyno.2005.03.023.
5	Epigenetic silencing of novel tumor suppressors in malignant melanoma. Cancer Res. 2006 Dec 1;66(23):11187-93. doi: 10.1158/0008-5472.CAN-06-1274.
6	ETV7-Mediated DNAJC15 Repression Leads to Doxorubicin Resistance in Breast Cancer Cells.Neoplasia. 2018 Aug;20(8):857-870. doi: 10.1016/j.neo.2018.06.008. Epub 2018 Jul 17.
7	Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
8	Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
9	Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
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	Epigenetic silencing of novel tumor suppressors in malignant melanoma. Cancer Res. 2006 Dec 1;66(23):11187-93. doi: 10.1158/0008-5472.CAN-06-1274.
12	Dose- and time-dependent effects of phenobarbital on gene expression profiling in human hepatoma HepaRG cells. Toxicol Appl Pharmacol. 2009 Feb 1;234(3):345-60.
13	Temporal changes in gene expression in the skin of patients treated with isotretinoin provide insight into its mechanism of action. Dermatoendocrinol. 2009 May;1(3):177-87.
14	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.
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	Bisphenol-A impairs cellular function and alters DNA methylation of stress pathway genes in first trimester trophoblast cells. Reprod Toxicol. 2018 Dec;82:72-79.
17	Neurotoxicity and underlying cellular changes of 21 mitochondrial respiratory chain inhibitors. Arch Toxicol. 2021 Feb;95(2):591-615. doi: 10.1007/s00204-020-02970-5. Epub 2021 Jan 29.
18	Functional lipidomics: Palmitic acid impairs hepatocellular carcinoma development by modulating membrane fluidity and glucose metabolism. Hepatology. 2017 Aug;66(2):432-448. doi: 10.1002/hep.29033. Epub 2017 Jun 16.