Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT7DPIVN)

• DOT Name: DnaJ homolog subfamily C member 14 (DNAJC14)
• Synonyms: DnaJ protein homolog 3; Dopamine receptor-interacting protein of 78 kDa; DRIP78; Human DnaJ protein 3; hDj-3
• Gene Name: DNAJC14
• Related Disease:
  Fibrolamellar liver cancer
  Huntington disease
  Pendred syndrome
  Primary peritoneal carcinoma
  Parkinsonian disorder
  Gastric cancer
  Parkinson disease
  Rheumatoid arthritis
• UniProt ID: DJC14_HUMAN
• Pfam ID: PF00226 ; PF14901
• Sequence:
  MAQKHPGERGLYGAHHSGGASLRTLGPSVDPEIPSFSGLRDSAGTAPNGTRCLTEHSGPK
  HTQHPNPAHWLDPSHGPPGGPGPPRDAEDPDQSETSSEEESGVDQELSKENETGNQKDGN
  SFLSIPSACNCQGTPGIPEGPYSEGGNGSSSNFCHHCTSPALGEDELEEEYDDEESLKFP
  SDFSRVSSGKKPPSRRQRHRFPTKEDTREGGRRDPRSPGRHRLGRKRSQADKRKGLGLWG
  AEELCQLGQAGFWWLIELLVLVGEYVETCGHLIYACRQLKSSDLDLFRVWMGVWTGRLGG
  WAQVMFQFLSQGFYCGVGLFTRFLKLLGALLLLALALFLGFLQLGWRFLVGLGDRLGWRD
  KATWLFSWLDSPALQRCLTLLRDSRPWQRLVRIVQWGWLELPWVKQNINRQGNAPVASGR
  YCQPEEEVARLLTMAGVPEDELNPFHVLGVEATASDVELKKAYRQLAVMVHPDKNHHPRA
  EEAFKVLRAAWDIVSNAEKRKEYEMKRMAENELSRSVNEFLSKLQDDLKEAMNTMMCSRC
  QGKHRRFEMDREPKSARYCAECNRLHPAEEGDFWAESSMLGLKITYFALMDGKVYDITEW
  AGCQRVGISPDTHRVPYHISFGSRIPGTRGRQRATPDAPPADLQDFLSRIFQVPPGQMPN
  GNFFAAPQPAPGAAAASKPNSTVPKGEAKPKRRKKVRRPFQR
• Function: Regulates the export of target proteins, such as DRD1, from the endoplasmic reticulum to the cell surface.
• Tissue Specificity: Highly expressed in pancreas and selectively expressed in brain, lung, liver, skeletal muscle and kidney.

Molecular Interaction Atlas (MIA) of This DOT

8 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Fibrolamellar liver cancer	DISUDA2P	Strong	Altered Expression	[1]
Huntington disease	DISQPLA4	Strong	Biomarker	[2]
Pendred syndrome	DISZ1MU8	moderate	Biomarker	[3]
Primary peritoneal carcinoma	DISKYEDV	moderate	Biomarker	[4]
Parkinsonian disorder	DISHGY45	Disputed	Genetic Variation	[5]
Gastric cancer	DISXGOUK	Limited	Biomarker	[6]
Parkinson disease	DISQVHKL	Limited	Biomarker	[7]
Rheumatoid arthritis	DISTSB4J	Limited	Biomarker	[8]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of DnaJ homolog subfamily C member 14 (DNAJC14).	[9]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of DnaJ homolog subfamily C member 14 (DNAJC14).	[10]
Marinol	DM70IK5	Approved	Marinol decreases the expression of DnaJ homolog subfamily C member 14 (DNAJC14).	[12]
Menadione	DMSJDTY	Approved	Menadione affects the expression of DnaJ homolog subfamily C member 14 (DNAJC14).	[13]
Bortezomib	DMNO38U	Approved	Bortezomib decreases the expression of DnaJ homolog subfamily C member 14 (DNAJC14).	[14]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of DnaJ homolog subfamily C member 14 (DNAJC14).	[15]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of DnaJ homolog subfamily C member 14 (DNAJC14).	[16]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of DnaJ homolog subfamily C member 14 (DNAJC14).	[11]

References

• [1] An acquired scaffolding function of the DNAJ-PKAc fusion contributes to oncogenic signaling in fibrolamellar carcinoma.Elife. 2019 May 7;8:e44187. doi: 10.7554/eLife.44187.
• [2] Suppression of protein aggregation by chaperone modification of high molecular weight complexes.Brain. 2012 Apr;135(Pt 4):1180-96. doi: 10.1093/brain/aws022. Epub 2012 Mar 6.
• [3] The HSP70 co-chaperone DNAJC14 targets misfolded pendrin for unconventional protein secretion.Nat Commun. 2016 Apr 25;7:11386. doi: 10.1038/ncomms11386.
• [4] Dopamine D1 receptor density in the mPFC responds to cognitive demands and receptorturnover contributes to general cognitive ability in mice.Sci Rep. 2018 Mar 14;8(1):4533. doi: 10.1038/s41598-018-22668-0.
• [5] DNAJC13 p.Asn855Ser, implicated in familial parkinsonism, alters membrane dynamics of sorting nexin 1.Neurosci Lett. 2019 Jul 27;706:114-122. doi: 10.1016/j.neulet.2019.04.043. Epub 2019 May 11.
• [6] HLJ1 (DNAJB4) Gene Is a Novel Biomarker Candidate in Breast Cancer.OMICS. 2017 May;21(5):257-265. doi: 10.1089/omi.2017.0016.
• [7] Whole genome expression profiling of the medial and lateral substantia nigra in Parkinson's disease.Neurogenetics. 2006 Mar;7(1):1-11. doi: 10.1007/s10048-005-0020-2. Epub 2006 Jan 12.
• [8] Isolation of an IgG monoclonal anti-dnaJ antibody from an immunoglobulin combinatorial library from a patient with rheumatoid arthritis.J Rheumatol. 1999 Jul;26(7):1439-45.
• [9] 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.
• [10] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [11] Prenatal arsenic exposure and the epigenome: identifying sites of 5-methylcytosine alterations that predict functional changes in gene expression in newborn cord blood and subsequent birth outcomes. Toxicol Sci. 2015 Jan;143(1):97-106. doi: 10.1093/toxsci/kfu210. Epub 2014 Oct 10.
• [12] THC exposure of human iPSC neurons impacts genes associated with neuropsychiatric disorders. Transl Psychiatry. 2018 Apr 25;8(1):89. doi: 10.1038/s41398-018-0137-3.
• [13] Global gene expression analysis reveals differences in cellular responses to hydroxyl- and superoxide anion radical-induced oxidative stress in caco-2 cells. Toxicol Sci. 2010 Apr;114(2):193-203. doi: 10.1093/toxsci/kfp309. Epub 2009 Dec 31.
• [14] The proapoptotic effect of zoledronic acid is independent of either the bone microenvironment or the intrinsic resistance to bortezomib of myeloma cells and is enhanced by the combination with arsenic trioxide. Exp Hematol. 2011 Jan;39(1):55-65.
• [15] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [16] 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.