Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT7WDJ5C)

• DOT Name: DnaJ homolog subfamily B member 5 (DNAJB5)
• Synonyms: Heat shock protein Hsp40-2; Heat shock protein Hsp40-3; Heat shock protein cognate 40; Hsc40
• Gene Name: DNAJB5
• Related Disease:
  Peripheral neuropathy
  Skeletal muscle disorder
  Ulcerative colitis
  Congenital contractural arachnodactyly
• UniProt ID: DNJB5_HUMAN
• Pfam ID: PF00226 ; PF01556
• Sequence:
  MGKDYYKILGIPSGANEDEIKKAYRKMALKYHPDKNKEPNAEEKFKEIAEAYDVLSDPKK
  RGLYDQYGEEGLKTGGGTSGGSSGSFHYTFHGDPHATFASFFGGSNPFDIFFASSRSTRP
  FSGFDPDDMDVDEDEDPFGAFGRFGFNGLSRGPRRAPEPLYPRRKVQDPPVVHELRVSLE
  EIYHGSTKRMKITRRRLNPDGRTVRTEDKILHIVIKRGWKEGTKITFPKEGDATPDNIPA
  DIVFVLKDKPHAHFRRDGTNVLYSALISLKEALCGCTVNIPTIDGRVIPLPCNDVIKPGT
  VKRLRGEGLPFPKVPTQRGDLIVEFKVRFPDRLTPQTRQILKQHLPCS

Molecular Interaction Atlas (MIA) of This DOT

4 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Peripheral neuropathy	DIS7KN5G	Strong	Genetic Variation	[1]
Skeletal muscle disorder	DISR9DGU	Strong	Genetic Variation	[1]
Ulcerative colitis	DIS8K27O	Strong	Altered Expression	[2]
Congenital contractural arachnodactyly	DISOM1K7	Limited	Altered Expression	[3]

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 B member 5 (DNAJB5).	[4]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of DnaJ homolog subfamily B member 5 (DNAJB5).	[5]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of DnaJ homolog subfamily B member 5 (DNAJB5).	[6]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of DnaJ homolog subfamily B member 5 (DNAJB5).	[7]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of DnaJ homolog subfamily B member 5 (DNAJB5).	[8]
Methotrexate	DM2TEOL	Approved	Methotrexate decreases the expression of DnaJ homolog subfamily B member 5 (DNAJB5).	[9]
Phenobarbital	DMXZOCG	Approved	Phenobarbital affects the expression of DnaJ homolog subfamily B member 5 (DNAJB5).	[10]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of DnaJ homolog subfamily B member 5 (DNAJB5).	[11]
Dihydrotestosterone	DM3S8XC	Phase 4	Dihydrotestosterone increases the expression of DnaJ homolog subfamily B member 5 (DNAJB5).	[12]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of DnaJ homolog subfamily B member 5 (DNAJB5).	[13]
Milchsaure	DM462BT	Investigative	Milchsaure increases the expression of DnaJ homolog subfamily B member 5 (DNAJB5).	[14]

References

• [1] Exome Sequence Analysis Suggests that Genetic Burden Contributes to Phenotypic Variability and Complex Neuropathy.Cell Rep. 2015 Aug 18;12(7):1169-83. doi: 10.1016/j.celrep.2015.07.023. Epub 2015 Aug 6.
• [2] From model cell line to in vivo gene expression: disease-related intestinal gene expression in IBD.Genes Immun. 2008 Apr;9(3):240-8. doi: 10.1038/gene.2008.11. Epub 2008 Mar 13.
• [3] MIR21 Drives Resistance to Heat Shock Protein 90 Inhibition in Cholangiocarcinoma.Gastroenterology. 2018 Mar;154(4):1066-1079.e5. doi: 10.1053/j.gastro.2017.10.043. Epub 2017 Nov 4.
• [4] The neuroprotective action of the mood stabilizing drugs lithium chloride and sodium valproate is mediated through the up-regulation of the homeodomain protein Six1. Toxicol Appl Pharmacol. 2009 Feb 15;235(1):124-34.
• [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] 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.
• [7] 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.
• [8] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [9] The contribution of methotrexate exposure and host factors on transcriptional variance in human liver. Toxicol Sci. 2007 Jun;97(2):582-94.
• [10] Reproducible chemical-induced changes in gene expression profiles in human hepatoma HepaRG cells under various experimental conditions. Toxicol In Vitro. 2009 Apr;23(3):466-75. doi: 10.1016/j.tiv.2008.12.018. Epub 2008 Dec 30.
• [11] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [12] LSD1 activates a lethal prostate cancer gene network independently of its demethylase function. Proc Natl Acad Sci U S A. 2018 May 1;115(18):E4179-E4188.
• [13] 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.
• [14] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.