Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTT7YCD2)

• DOT Name: DnaJ homolog subfamily A member 4 (DNAJA4)
• Gene Name: DNAJA4
• Related Disease: Human papillomavirus infection
• UniProt ID: DNJA4_HUMAN
• Pfam ID: PF00226 ; PF01556 ; PF00684
• Sequence:
  MVKETQYYDILGVKPSASPEEIKKAYRKLALKYHPDKNPDEGEKFKLISQAYEVLSDPKK
  RDVYDQGGEQAIKEGGSGSPSFSSPMDIFDMFFGGGGRMARERRGKNVVHQLSVTLEDLY
  NGVTKKLALQKNVICEKCEGVGGKKGSVEKCPLCKGRGMQIHIQQIGPGMVQQIQTVCIE
  CKGQGERINPKDRCESCSGAKVIREKKIIEVHVEKGMKDGQKILFHGEGDQEPELEPGDV
  IIVLDQKDHSVFQRRGHDLIMKMKIQLSEALCGFKKTIKTLDNRILVITSKAGEVIKHGD
  LRCVRDEGMPIYKAPLEKGILIIQFLVIFPEKHWLSLEKLPQLEALLPPRQKVRITDDMD
  QVELKEFCPNEQNWRQHREAYEEDEDGPQAGVQCQTA
• Reactome Pathway: HSP90 chaperone cycle for steroid hormone receptors (SHR) in the presence of ligand (R-HSA-3371497)

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Human papillomavirus infection	DISX61LX	Limited	Biomarker	[1]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the methylation of DnaJ homolog subfamily A member 4 (DNAJA4).	[2]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of DnaJ homolog subfamily A member 4 (DNAJA4).	[9]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of DnaJ homolog subfamily A member 4 (DNAJA4).	[3]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of DnaJ homolog subfamily A member 4 (DNAJA4).	[4]
Triclosan	DMZUR4N	Approved	Triclosan decreases the expression of DnaJ homolog subfamily A member 4 (DNAJA4).	[5]
Decitabine	DMQL8XJ	Approved	Decitabine increases the expression of DnaJ homolog subfamily A member 4 (DNAJA4).	[6]
Niclosamide	DMJAGXQ	Approved	Niclosamide decreases the expression of DnaJ homolog subfamily A member 4 (DNAJA4).	[7]
Amphotericin B	DMTAJQE	Approved	Amphotericin B increases the expression of DnaJ homolog subfamily A member 4 (DNAJA4).	[8]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of DnaJ homolog subfamily A member 4 (DNAJA4).	[10]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of DnaJ homolog subfamily A member 4 (DNAJA4).	[11]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of DnaJ homolog subfamily A member 4 (DNAJA4).	[12]
Milchsaure	DM462BT	Investigative	Milchsaure increases the expression of DnaJ homolog subfamily A member 4 (DNAJA4).	[13]
chloropicrin	DMSGBQA	Investigative	chloropicrin increases the expression of DnaJ homolog subfamily A member 4 (DNAJA4).	[14]

References

• [1] DNAJA4 deficiency enhances NF-kappa B-related growth arrest induced by hyperthermia in human keratinocytes.J Dermatol Sci. 2018 Sep;91(3):256-267. doi: 10.1016/j.jdermsci.2018.05.006. Epub 2018 May 23.
• [2] Integrative omics data analyses of repeated dose toxicity of valproic acid in vitro reveal new mechanisms of steatosis induction. Toxicology. 2018 Jan 15;393:160-170.
• [3] Gene expression analysis of precision-cut human liver slices indicates stable expression of ADME-Tox related genes. Toxicol Appl Pharmacol. 2011 May 15;253(1):57-69.
• [4] 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.
• [5] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [6] Characterization of DOK1, a candidate tumor suppressor gene, in epithelial ovarian cancer. Mol Oncol. 2011 Oct;5(5):438-53. doi: 10.1016/j.molonc.2011.07.003. Epub 2011 Jul 26.
• [7] 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.
• [8] Differential expression of microRNAs and their predicted targets in renal cells exposed to amphotericin B and its complex with copper (II) ions. Toxicol Mech Methods. 2017 Sep;27(7):537-543. doi: 10.1080/15376516.2017.1333554. Epub 2017 Jun 8.
• [9] 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.
• [10] 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.
• [11] Comparison of transcriptome expression alterations by chronic exposure to low-dose bisphenol A in different subtypes of breast cancer cells. Toxicol Appl Pharmacol. 2019 Dec 15;385:114814. doi: 10.1016/j.taap.2019.114814. Epub 2019 Nov 9.
• [12] Gene expression changes in primary human nasal epithelial cells exposed to formaldehyde in vitro. Toxicol Lett. 2010 Oct 5;198(2):289-95.
• [13] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.
• [14] Transcriptomic analysis of human primary bronchial epithelial cells after chloropicrin treatment. Chem Res Toxicol. 2015 Oct 19;28(10):1926-35.