Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTCKFOZ0)

• DOT Name: DnaJ homolog subfamily C member 1 (DNAJC1)
• Synonyms: DnaJ protein homolog MTJ1
• Gene Name: DNAJC1
• Related Disease:
  Breast carcinoma
  Melanoma
  Parkinson disease
  Acute myelogenous leukaemia
• UniProt ID: DNJC1_HUMAN
• PDB ID: 2CQQ; 2CQR
• Pfam ID: PF00226 ; PF00249
• Sequence:
  MTAPCSQPAQLPGRRQLGLVPFPPPPPRTPLLWLLLLLLAAVAPARGWESGDLELFDLVE
  EVQLNFYQFLGVQQDASSADIRKAYRKLSLTLHPDKNKDENAETQFRQLVAIYEVLKDDE
  RRQRYDDILINGLPDWRQPVFYYRRVRKMSNAELALLLFIILTVGHYAVVWSIYLEKQLD
  ELLSRKKREKKKKTGSKSVDVSKLGASEKNERLLMKPQWHDLLPCKLGIWFCLTLKALPH
  LIQDAGQFYAKYKETRLKEKEDALTRTELETLQKQKKVKKPKPEFPVYTPLETTYIQSYD
  HGTSIEEIEEQMDDWLENRNRTQKKQAPEWTEEDLSQLTRSMVKFPGGTPGRWEKIAHEL
  GRSVTDVTTKAKQLKDSVTCSPGMVRLSELKSTVQNSRPIKTATTLPDDMITQREDAEGV
  AAEEEQEGDSGEQETGATDARPRRRKPARLLEATAKPEPEEKSRAKRQKDFDIAEQNESS
  DEESLRKERARSAEEPWTQNQQKLLELALQQYPRGSSDRWDKIARCVPSKSKEDCIARYK
  LLVELVQKKKQAKS
• Function: May modulate protein synthesis.
• KEGG Pathway: Protein processing in endoplasmic reticulum (hsa04141)

Molecular Interaction Atlas (MIA) of This DOT

4 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Breast carcinoma	DIS2UE88	Strong	Genetic Variation	[1]
Melanoma	DIS1RRCY	Strong	Biomarker	[2]
Parkinson disease	DISQVHKL	Strong	Genetic Variation	[3]
Acute myelogenous leukaemia	DISCSPTN	Limited	Genetic Variation	[4]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the methylation of DnaJ homolog subfamily C member 1 (DNAJC1).	[5]
Quercetin	DM3NC4M	Approved	Quercetin increases the phosphorylation of DnaJ homolog subfamily C member 1 (DNAJC1).	[11]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the methylation of DnaJ homolog subfamily C member 1 (DNAJC1).	[18]
Coumarin	DM0N8ZM	Investigative	Coumarin decreases the phosphorylation of DnaJ homolog subfamily C member 1 (DNAJC1).	[11]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of DnaJ homolog subfamily C member 1 (DNAJC1).	[6]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of DnaJ homolog subfamily C member 1 (DNAJC1).	[7]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of DnaJ homolog subfamily C member 1 (DNAJC1).	[8]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of DnaJ homolog subfamily C member 1 (DNAJC1).	[9]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of DnaJ homolog subfamily C member 1 (DNAJC1).	[10]
Diethylstilbestrol	DMN3UXQ	Approved	Diethylstilbestrol decreases the expression of DnaJ homolog subfamily C member 1 (DNAJC1).	[12]
Nefazodone	DM4ZS8M	Approved	Nefazodone increases the expression of DnaJ homolog subfamily C member 1 (DNAJC1).	[13]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of DnaJ homolog subfamily C member 1 (DNAJC1).	[14]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of DnaJ homolog subfamily C member 1 (DNAJC1).	[15]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 increases the expression of DnaJ homolog subfamily C member 1 (DNAJC1).	[16]
THAPSIGARGIN	DMDMQIE	Preclinical	THAPSIGARGIN affects the expression of DnaJ homolog subfamily C member 1 (DNAJC1).	[17]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of DnaJ homolog subfamily C member 1 (DNAJC1).	[19]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of DnaJ homolog subfamily C member 1 (DNAJC1).	[20]
Coumestrol	DM40TBU	Investigative	Coumestrol decreases the expression of DnaJ homolog subfamily C member 1 (DNAJC1).	[21]
geraniol	DMS3CBD	Investigative	geraniol increases the expression of DnaJ homolog subfamily C member 1 (DNAJC1).	[22]

References

• [1] Association analysis identifies 65 new breast cancer risk loci.Nature. 2017 Nov 2;551(7678):92-94. doi: 10.1038/nature24284. Epub 2017 Oct 23.
• [2] Aggressiveness of human melanoma xenograft models is promoted by aneuploidy-driven gene expression deregulation.Oncotarget. 2012 Apr;3(4):399-413. doi: 10.18632/oncotarget.473.
• [3] Genome-wide genotyping in Parkinson's disease and neurologically normal controls: first stage analysis and public release of data.Lancet Neurol. 2006 Nov;5(11):911-6. doi: 10.1016/S1474-4422(06)70578-6.
• [4] Genome-wide haplotype association study identify the FGFR2 gene as a risk gene for acute myeloid leukemia.Oncotarget. 2017 Jan 31;8(5):7891-7899. doi: 10.18632/oncotarget.13631.
• [5] 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.
• [6] 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.
• [7] 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.
• [8] Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
• [9] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [10] Low doses of cisplatin induce gene alterations, cell cycle arrest, and apoptosis in human promyelocytic leukemia cells. Biomark Insights. 2016 Aug 24;11:113-21.
• [11] 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.
• [12] 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.
• [13] 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.
• [14] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [15] Transcriptional signature of human macrophages exposed to the environmental contaminant benzo(a)pyrene. Toxicol Sci. 2010 Apr;114(2):247-59.
• [16] BET bromodomain inhibition targets both c-Myc and IL7R in high-risk acute lymphoblastic leukemia. Blood. 2012 Oct 4;120(14):2843-52.
• [17] DON shares a similar mode of action as the ribotoxic stress inducer anisomycin while TBTO shares ER stress patterns with the ER stress inducer thapsigargin based on comparative gene expression profiling in Jurkat T cells. Toxicol Lett. 2014 Jan 30;224(3):395-406. doi: 10.1016/j.toxlet.2013.11.005. Epub 2013 Nov 15.
• [18] DNA methylome-wide alterations associated with estrogen receptor-dependent effects of bisphenols in breast cancer. Clin Epigenetics. 2019 Oct 10;11(1):138. doi: 10.1186/s13148-019-0725-y.
• [19] From transient transcriptome responses to disturbed neurodevelopment: role of histone acetylation and methylation as epigenetic switch between reversible and irreversible drug effects. Arch Toxicol. 2014 Jul;88(7):1451-68.
• [20] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.
• [21] Pleiotropic combinatorial transcriptomes of human breast cancer cells exposed to mixtures of dietary phytoestrogens. Food Chem Toxicol. 2009 Apr;47(4):787-95.
• [22] Geraniol suppresses prostate cancer growth through down-regulation of E2F8. Cancer Med. 2016 Oct;5(10):2899-2908.