Details of Drug Off-Target (DOT)

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

• DOT Name: DnaJ homolog subfamily C member 27 (DNAJC27)
• Synonyms: Rab and DnaJ domain-containing protein
• Gene Name: DNAJC27
• Related Disease:
  Alzheimer disease
  Breast cancer
  Breast carcinoma
  Neoplasm
  Non-insulin dependent diabetes
  Obesity
• UniProt ID: DJC27_HUMAN
• PDB ID: 2YS8
• Pfam ID: PF00226 ; PF00071
• Sequence:
  MEANMPKRKEPGRSLRIKVISMGNAEVGKSCIIKRYCEKRFVSKYLATIGIDYGVTKVHV
  RDREIKVNIFDMAGHPFFYEVRNEFYKDTQGVILVYDVGQKDSFDALDAWLAEMKQELGP
  HGNMENIIFVVCANKIDCTKHRCVDESEGRLWAESKGFLYFETSAQTGEGINEMFQTFYI
  SIVDLCENGGKRPTTNSSASFTKEQADAIRRIRNSKDSWDMLGVKPGASRDEVNKAYRKL
  AVLLHPDKCVAPGSEDAFKAVVNARTALLKNIK
• Function: GTPase which can activate the MEK/ERK pathway and induce cell transformation when overexpressed. May act as a nuclear scaffold for MAPK1, probably by association with MAPK1 nuclear export signal leading to enhanced ERK1/ERK2 signaling.
• Tissue Specificity: Overexpressed in gastrointestinal cancers; expression correlates with later tumor-node-metastasis stages of colorectal cancers.

Molecular Interaction Atlas (MIA) of This DOT

6 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Alzheimer disease	DISF8S70	Strong	Genetic Variation	[1]
Breast cancer	DIS7DPX1	Strong	Altered Expression	[2]
Breast carcinoma	DIS2UE88	Strong	Altered Expression	[2]
Neoplasm	DISZKGEW	Strong	Altered Expression	[2]
Non-insulin dependent diabetes	DISK1O5Z	Strong	Altered Expression	[3]
Obesity	DIS47Y1K	Strong	Biomarker	[3]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the expression of DnaJ homolog subfamily C member 27 (DNAJC27).	[4]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of DnaJ homolog subfamily C member 27 (DNAJC27).	[5]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of DnaJ homolog subfamily C member 27 (DNAJC27).	[6]
Cisplatin	DMRHGI9	Approved	Cisplatin affects the expression of DnaJ homolog subfamily C member 27 (DNAJC27).	[7]
Decitabine	DMQL8XJ	Approved	Decitabine affects the expression of DnaJ homolog subfamily C member 27 (DNAJC27).	[7]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of DnaJ homolog subfamily C member 27 (DNAJC27).	[9]
Resorcinol	DMM37C0	Investigative	Resorcinol decreases the expression of DnaJ homolog subfamily C member 27 (DNAJC27).	[11]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of DnaJ homolog subfamily C member 27 (DNAJC27).	[8]
Coumarin	DM0N8ZM	Investigative	Coumarin decreases the phosphorylation of DnaJ homolog subfamily C member 27 (DNAJC27).	[10]

References

• [1] Genetic variation at the CELF1 (CUGBP, elav-like family member 1 gene) locus is genome-wide associated with Alzheimer's disease and obesity.Am J Med Genet B Neuropsychiatr Genet. 2014 Jun;165B(4):283-93. doi: 10.1002/ajmg.b.32234. Epub 2014 May 1.
• [2] Small GTPase RBJ promotes cancer progression by mobilizing MDSCs via IL-6.Oncoimmunology. 2016 Dec 23;6(1):e1245265. doi: 10.1080/2162402X.2016.1245265. eCollection 2017.
• [3] Increased Circulation and Adipose Tissue Levels of DNAJC27/RBJ in Obesity and Type 2-Diabetes.Front Endocrinol (Lausanne). 2018 Aug 7;9:423. doi: 10.3389/fendo.2018.00423. eCollection 2018.
• [4] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [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] Acute hypersensitivity of pluripotent testicular cancer-derived embryonal carcinoma to low-dose 5-aza deoxycytidine is associated with global DNA Damage-associated p53 activation, anti-pluripotency and DNA demethylation. PLoS One. 2012;7(12):e53003. doi: 10.1371/journal.pone.0053003. Epub 2012 Dec 27.
• [8] 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.
• [9] Gene expression changes in primary human nasal epithelial cells exposed to formaldehyde in vitro. Toxicol Lett. 2010 Oct 5;198(2):289-95.
• [10] 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.
• [11] A transcriptomics-based in vitro assay for predicting chemical genotoxicity in vivo. Carcinogenesis. 2012 Jul;33(7):1421-9.