Details of Drug Off-Target (DOT)

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

• DOT Name: Protein Jade-1 (JADE1)
• Synonyms: Jade family PHD finger protein 1; PHD finger protein 17
• Gene Name: JADE1
• Related Disease:
  Clear cell renal carcinoma
  Kidney cancer
  Nephropathy
  Renal carcinoma
  Renal cell carcinoma
  Von hippel-lindau disease
  Pancreatic cancer
  Pancreatic ductal carcinoma
  Kidney neoplasm
  Neoplasm
• UniProt ID: JADE1_HUMAN
• Pfam ID: PF10513 ; PF13831 ; PF13832
• Sequence:
  MKRGRLPSSSEDSDDNGSLSTTWSQNSRSQHRRSSCSRHEDRKPSEVFRTDLITAMKLHD
  SYQLNPDEYYVLADPWRQEWEKGVQVPVSPGTIPQPVARVVSEEKSLMFIRPKKYIVSSG
  SEPPELGYVDIRTLADSVCRYDLNDMDAAWLELTNEEFKEMGMPELDEYTMERVLEEFEQ
  RCYDNMNHAIETEEGLGIEYDEDVVCDVCQSPDGEDGNEMVFCDKCNICVHQACYGILKV
  PEGSWLCRTCALGVQPKCLLCPKKGGAMKPTRSGTKWVHVSCALWIPEVSIGSPEKMEPI
  TKVSHIPSSRWALVCSLCNEKFGASIQCSVKNCRTAFHVTCAFDRGLEMKTILAENDEVK
  FKSYCPKHSSHRKPEESLGKGAAQENGAPECSPRNPLEPFASLEQNREEAHRVSVRKQKL
  QQLEDEFYTFVNLLDVARALRLPEEVVDFLYQYWKLKRKVNFNKPLITPKKDEEDNLAKR
  EQDVLFRRLQLFTHLRQDLERVRNLTYMVTRREKIKRSVCKVQEQIFNLYTKLLEQERVS
  GVPSSCSSSSLENMLLFNSPSVGPDAPKIEDLKWHSAFFRKQMGTSLVHSLKKPHKRDPL
  QNSPGSEGKTLLKQPDLCGRREGMVVPESFLGLEKTFAEARLISAQQKNGVVMPDHGKRR
  DNRFHCDLIKGDLKDKSFKQSHKPLRSTDVSQRHLDNTRAATSPGVGQSAPGTRKEIVPK
  CNGSLIKVNYNQTAVKVPTTPASPVKNWGGFRIPKKGERQQQGEAHDGACHQHSDYPYLG
  LGRVPAKERAKSKLKSDNENDGYVPDVEMSDSESEASEKKCIHTSSTISRRTDIIRRSIL
  AS
• Function: Scaffold subunit of some HBO1 complexes, which have a histone H4 acetyltransferase activity. Plays a key role in HBO1 complex by directing KAT7/HBO1 specificity towards histone H4 acetylation (H4K5ac, H4K8ac and H4K12ac), regulating DNA replication initiation, regulating DNA replication initiation. May also promote acetylation of nucleosomal histone H4 by KAT5. Promotes apoptosis. May act as a renal tumor suppressor. Negatively regulates canonical Wnt signaling; at least in part, cooperates with NPHP4 in this function.
• Tissue Specificity: Highly expressed in kidney. Also present in pancreas, liver and heart (at protein level). Down-regulated in renal cancer cells.
• Reactome Pathway: HATs acetylate histones (R-HSA-3214847)

Molecular Interaction Atlas (MIA) of This DOT

10 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Clear cell renal carcinoma	DISBXRFJ	Strong	Biomarker	[1]
Kidney cancer	DISBIPKM	Strong	Altered Expression	[2]
Nephropathy	DISXWP4P	Strong	Altered Expression	[3]
Renal carcinoma	DISER9XT	Strong	Altered Expression	[2]
Renal cell carcinoma	DISQZ2X8	Strong	Biomarker	[1]
Von hippel-lindau disease	DIS6ZFQQ	Strong	Altered Expression	[4]
Pancreatic cancer	DISJC981	moderate	Biomarker	[5]
Pancreatic ductal carcinoma	DIS26F9Q	moderate	Biomarker	[5]
Kidney neoplasm	DISBNZTN	Limited	Biomarker	[2]
Neoplasm	DISZKGEW	Limited	Biomarker	[6]

This DOT Affected the Drug Response of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Chlorothiazide	DMLHESP	Approved	Protein Jade-1 (JADE1) increases the Metabolic disorder ADR of Chlorothiazide.	[25]

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 Protein Jade-1 (JADE1).	[7]
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of Protein Jade-1 (JADE1).	[13]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Protein Jade-1 (JADE1).	[8]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Protein Jade-1 (JADE1).	[9]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Protein Jade-1 (JADE1).	[10]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Protein Jade-1 (JADE1).	[11]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Protein Jade-1 (JADE1).	[12]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of Protein Jade-1 (JADE1).	[14]
Progesterone	DMUY35B	Approved	Progesterone increases the expression of Protein Jade-1 (JADE1).	[15]
Dexamethasone	DMMWZET	Approved	Dexamethasone increases the expression of Protein Jade-1 (JADE1).	[16]
GSK2110183	DMZHB37	Phase 2	GSK2110183 decreases the expression of Protein Jade-1 (JADE1).	[17]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Protein Jade-1 (JADE1).	[18]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Protein Jade-1 (JADE1).	[19]
PMID28870136-Compound-48	DMPIM9L	Patented	PMID28870136-Compound-48 increases the expression of Protein Jade-1 (JADE1).	[20]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Protein Jade-1 (JADE1).	[21]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of Protein Jade-1 (JADE1).	[22]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of Protein Jade-1 (JADE1).	[23]
Microcystin-LR	DMTMLRN	Investigative	Microcystin-LR decreases the expression of Protein Jade-1 (JADE1).	[24]

References

• [1] Antitumor effect and biological pathways of a recombinant adeno-associated virus as a human renal cell carcinoma suppressor.Tumour Biol. 2014 Nov;35(11):10993-1003. doi: 10.1007/s13277-014-2393-z. Epub 2014 Aug 5.
• [2] Structural basis for renal cancer by the dynamics of pVHL-dependent JADE1 stabilization and -catenin regulation.Prog Biophys Mol Biol. 2019 Aug;145:65-77. doi: 10.1016/j.pbiomolbio.2018.12.005. Epub 2018 Dec 7.
• [3] Polycystin-1 regulates the stability and ubiquitination of transcription factor Jade-1.Hum Mol Genet. 2012 Dec 15;21(26):5456-71. doi: 10.1093/hmg/dds391. Epub 2012 Sep 21.
• [4] von Hippel-Lindau partner Jade-1 is a transcriptional co-activator associated with histone acetyltransferase activity.J Biol Chem. 2004 Dec 31;279(53):56032-41. doi: 10.1074/jbc.M410487200. Epub 2004 Oct 22.
• [5] Integrated microRNA-mRNA analysis of pancreatic ductal adenocarcinoma.Genet Mol Res. 2015 Aug 28;14(3):10288-97. doi: 10.4238/2015.August.28.14.
• [6] Candidate tumor suppressor and pVHL partner Jade-1 binds and inhibits AKT in renal cell carcinoma.Cancer Res. 2013 Sep 1;73(17):5371-80. doi: 10.1158/0008-5472.CAN-12-4707. Epub 2013 Jul 1.
• [7] 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.
• [8] Integrative "-Omics" analysis in primary human hepatocytes unravels persistent mechanisms of cyclosporine A-induced cholestasis. Chem Res Toxicol. 2016 Dec 19;29(12):2164-2174.
• [9] Development of a neural teratogenicity test based on human embryonic stem cells: response to retinoic acid exposure. Toxicol Sci. 2011 Dec;124(2):370-7.
• [10] Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
• [11] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [12] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [13] 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.
• [14] 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.
• [15] Unique transcriptome, pathways, and networks in the human endometrial fibroblast response to progesterone in endometriosis. Biol Reprod. 2011 Apr;84(4):801-15.
• [16] Identification of mechanisms of action of bisphenol a-induced human preadipocyte differentiation by transcriptional profiling. Obesity (Silver Spring). 2014 Nov;22(11):2333-43.
• [17] Novel ATP-competitive Akt inhibitor afuresertib suppresses the proliferation of malignant pleural mesothelioma cells. Cancer Med. 2017 Nov;6(11):2646-2659. doi: 10.1002/cam4.1179. Epub 2017 Sep 27.
• [18] Transcriptional signature of human macrophages exposed to the environmental contaminant benzo(a)pyrene. Toxicol Sci. 2010 Apr;114(2):247-59.
• [19] Bromodomain-containing protein 4 (BRD4) regulates RNA polymerase II serine 2 phosphorylation in human CD4+ T cells. J Biol Chem. 2012 Dec 14;287(51):43137-55.
• [20] Oxidative stress modulates theophylline effects on steroid responsiveness. Biochem Biophys Res Commun. 2008 Dec 19;377(3):797-802.
• [21] Bisphenol A and bisphenol S induce distinct transcriptional profiles in differentiating human primary preadipocytes. PLoS One. 2016 Sep 29;11(9):e0163318.
• [22] 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.
• [23] Gene expression changes in primary human nasal epithelial cells exposed to formaldehyde in vitro. Toxicol Lett. 2010 Oct 5;198(2):289-95.
• [24] Cytotoxic Effects of Environmental Toxins on Human Glial Cells. Neurotox Res. 2017 Feb;31(2):245-258. doi: 10.1007/s12640-016-9678-5. Epub 2016 Oct 29.
• [25] Genome-wide association analyses suggest NELL1 influences adverse metabolic response to HCTZ in African Americans. Pharmacogenomics J. 2014 Feb;14(1):35-40. doi: 10.1038/tpj.2013.3. Epub 2013 Feb 12.