Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTA1F9IN)

• DOT Name: DnaJ homolog subfamily C member 16 (DNAJC16)
• Synonyms: Endoplasmic reticulum DNA J domain-containing protein 8; ER-resident protein ERdj8; ERdj8
• Gene Name: DNAJC16
• Related Disease: Chronic kidney disease
• UniProt ID: DJC16_HUMAN
• Pfam ID: PF00226 ; PF00085
• Sequence:
  MEVRKLSISWQFLIVLVLILQILSALDFDPYRVLGVSRTASQADIKKAYKKLAREWHPDK
  NKDPGAEDKFIQISKAYEILSNEEKRSNYDQYGDAGENQGYQKQQQQREYRFRHFHENFY
  FDESFFHFPFNSERRDSIDEKYLLHFSHYVNEVVPDSFKKPYLIKITSDWCFSCIHIEPV
  WKEVIQELEELGVGIGVVHAGYERRLAHHLGAHSTPSILGIINGKISFFHNAVVRENLRQ
  FVESLLPGNLVEKVTNKNYVRFLSGWQQENKPHVLLFDQTPIVPLLYKLTAFAYKDYLSF
  GYVYVGLRGTEEMTRRYNINIYAPTLLVFKEHINRPADVIQARGMKKQIIDDFITRNKYL
  LAARLTSQKLFHELCPVKRSHRQRKYCVVLLTAETTKLSKPFEAFLSFALANTQDTVRFV
  HVYSNRQQEFADTLLPDSEAFQGKSAVSILERRNTAGRVVYKTLEDPWIGSESDKFILLG
  YLDQLRKDPALLSSEAVLPDLTDELAPVFLLRWFYSASDYISDCWDSIFHNNWREMMPLL
  SLIFSALFILFGTVIVQAFSDSNDERESSPPEKEEAQEKTGKTEPSFTKENSSKIPKKGF
  VEVTELTDVTYTSNLVRLRPGHMNVVLILSNSTKTSLLQKFALEVYTFTGSSCLHFSFLS
  LDKHREWLEYLLEFAQDAAPIPNQYDKHFMERDYTGYVLALNGHKKYFCLFKPQKTVEEE
  EAIGSCSDVDSSLYLGESRGKPSCGLGSRPIKGKLSKLSLWMERLLEGSLQRFYIPSWPE
  LD
• Function: Plays an important role in regulating the size of autophagosomes during the formation process.

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Chronic kidney disease	DISW82R7	Limited	Genetic Variation	[1]

4 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 C member 16 (DNAJC16).	[2]
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of DnaJ homolog subfamily C member 16 (DNAJC16).	[5]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 affects the phosphorylation of DnaJ homolog subfamily C member 16 (DNAJC16).	[6]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of DnaJ homolog subfamily C member 16 (DNAJC16).	[7]

4 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 16 (DNAJC16).	[3]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of DnaJ homolog subfamily C member 16 (DNAJC16).	[4]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A affects the expression of DnaJ homolog subfamily C member 16 (DNAJC16).	[8]
Coumestrol	DM40TBU	Investigative	Coumestrol decreases the expression of DnaJ homolog subfamily C member 16 (DNAJC16).	[9]

References

• [1] Genome-wide association and functional follow-up reveals new loci for kidney function.PLoS Genet. 2012;8(3):e1002584. doi: 10.1371/journal.pgen.1002584. Epub 2012 Mar 29.
• [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] 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.
• [4] 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.
• [5] 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.
• [6] 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.
• [7] 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.
• [8] A trichostatin A expression signature identified by TempO-Seq targeted whole transcriptome profiling. PLoS One. 2017 May 25;12(5):e0178302. doi: 10.1371/journal.pone.0178302. eCollection 2017.
• [9] Pleiotropic combinatorial transcriptomes of human breast cancer cells exposed to mixtures of dietary phytoestrogens. Food Chem Toxicol. 2009 Apr;47(4):787-95.