Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTKMZ5K5)

• DOT Name: Interleukin enhancer-binding factor 3 (ILF3)
• Synonyms: Double-stranded RNA-binding protein 76; DRBP76; M-phase phosphoprotein 4; MPP4; Nuclear factor associated with dsRNA; NFAR; Nuclear factor of activated T-cells 90 kDa; NF-AT-90; Translational control protein 80; TCP80
• Gene Name: ILF3
• Related Disease:
  Acute erythroid leukemia
  Advanced cancer
  Bladder cancer
  Breast carcinoma
  Cardiac failure
  Congestive heart failure
  Dengue
  Epithelial ovarian cancer
  Esophageal squamous cell carcinoma
  Hepatocellular carcinoma
  High blood pressure
  HIV infectious disease
  Lung cancer
  Lung carcinoma
  Malaria
  Myocardial infarction
  Ovarian cancer
  Prostate cancer
  Prostate carcinoma
  Rheumatoid arthritis
  Sjogren syndrome
  Type-1/2 diabetes
  Urinary bladder cancer
  Urinary bladder neoplasm
  Bacterial infection
  Chronic kidney disease
  Influenza
  Stroke
  Gastric cancer
  Stomach cancer
  Breast cancer
  Breast neoplasm
  Clear cell renal carcinoma
  Colorectal carcinoma
  Hepatitis C virus infection
  Melanoma
  Nasopharyngeal carcinoma
  Neoplasm
• UniProt ID: ILF3_HUMAN
• PDB ID: 2L33; 3P1X; 7RJM; 7RJQ
• Pfam ID: PF00035 ; PF20965 ; PF07528
• Sequence:
  MRPMRIFVNDDRHVMAKHSSVYPTQEELEAVQNMVSHTERALKAVSDWIDEQEKGSSEQA
  ESDNMDVPPEDDSKEGAGEQKTEHMTRTLRGVMRVGLVAKGLLLKGDLDLELVLLCKEKP
  TTALLDKVADNLAIQLAAVTEDKYEILQSVDDAAIVIKNTKEPPLSLTIHLTSPVVREEM
  EKVLAGETLSVNDPPDVLDRQKCLAALASLRHAKWFQARANGLKSCVIVIRVLRDLCTRV
  PTWGPLRGWPLELLCEKSIGTANRPMGAGEALRRVLECLASGIVMPDGSGIYDPCEKEAT
  DAIGHLDRQQREDITQSAQHALRLAAFGQLHKVLGMDPLPSKMPKKPKNENPVDYTVQIP
  PSTTYAITPMKRPMEEDGEEKSPSKKKKKIQKKEEKAEPPQAMNALMRLNQLKPGLQYKL
  VSQTGPVHAPIFTMSVEVDGNSFEASGPSKKTAKLHVAVKVLQDMGLPTGAEGRDSSKGE
  DSAEETEAKPAVVAPAPVVEAVSTPSAAFPSDATAEQGPILTKHGKNPVMELNEKRRGLK
  YELISETGGSHDKRFVMEVEVDGQKFQGAGSNKKVAKAYAALAALEKLFPDTPLALDANK
  KKRAPVPVRGGPKFAAKPHNPGFGMGGPMHNEVPPPPNLRGRGRGGSIRGRGRGRGFGGA
  NHGGYMNAGAGYGSYGYGGNSATAGYSQFYSNGGHSGNASGGGGGGGGGSSGYGSYYQGD
  NYNSPVPPKHAGKKQPHGGQQKPSYGSGYQSHQGQQQSYNQSPYSNYGPPQGKQKGYNHG
  QGSYSYSNSYNSPGGGGGSDYNYESKFNYSGSGGRSGGNSYGSGGASYNPGSHGGYGGGS
  GGGSSYQGKQGGYSQSNYNSPGSGQNYSGPPSSYQSSQGGYGRNADHSMNYQYR
• Function: RNA-binding protein that plays an essential role in the biogenesis of circular RNAs (circRNAs) which are produced by back-splicing circularization of pre-mRNAs. Within the nucleus, promotes circRNAs processing by stabilizing the regulatory elements residing in the flanking introns of the circularized exons. Plays thereby a role in the back-splicing of a subset of circRNAs. As a consequence, participates in a wide range of transcriptional and post-transcriptional processes. Binds to poly-U elements and AU-rich elements (AREs) in the 3'-UTR of target mRNAs. Upon viral infection, ILF3 accumulates in the cytoplasm and participates in the innate antiviral response. Mechanistically, ILF3 becomes phosphorylated and activated by the double-stranded RNA-activated protein kinase/PKR which releases ILF3 from cellular mature circRNAs. In turn, unbound ILF3 molecules are able to interact with and thus inhibit viral mRNAs ; (Microbial infection) Plays a positive role in HIV-1 virus production by binding to and thereby stabilizing HIV-1 RNA, together with ILF3.
• Tissue Specificity: Ubiquitous.
• Reactome Pathway:
  PKR-mediated signaling (R-HSA-9833482)
  Regulation of CDH11 gene transcription (R-HSA-9762293)

Molecular Interaction Atlas (MIA) of This DOT

38 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Acute erythroid leukemia	DISZFC1O	Strong	Altered Expression	[1]
Advanced cancer	DISAT1Z9	Strong	Altered Expression	[2]
Bladder cancer	DISUHNM0	Strong	Biomarker	[3]
Breast carcinoma	DIS2UE88	Strong	Altered Expression	[4]
Cardiac failure	DISDC067	Strong	Biomarker	[5]
Congestive heart failure	DIS32MEA	Strong	Biomarker	[5]
Dengue	DISKH221	Strong	Biomarker	[6]
Epithelial ovarian cancer	DIS56MH2	Strong	Altered Expression	[7]
Esophageal squamous cell carcinoma	DIS5N2GV	Strong	Biomarker	[8]
Hepatocellular carcinoma	DIS0J828	Strong	Biomarker	[9]
High blood pressure	DISY2OHH	Strong	Genetic Variation	[10]
HIV infectious disease	DISO97HC	Strong	Biomarker	[11]
Lung cancer	DISCM4YA	Strong	Biomarker	[12]
Lung carcinoma	DISTR26C	Strong	Biomarker	[12]
Malaria	DISQ9Y50	Strong	Biomarker	[13]
Myocardial infarction	DIS655KI	Strong	Genetic Variation	[10]
Ovarian cancer	DISZJHAP	Strong	Altered Expression	[7]
Prostate cancer	DISF190Y	Strong	Biomarker	[14]
Prostate carcinoma	DISMJPLE	Strong	Biomarker	[14]
Rheumatoid arthritis	DISTSB4J	Strong	Genetic Variation	[15]
Sjogren syndrome	DISUBX7H	Strong	Biomarker	[16]
Type-1/2 diabetes	DISIUHAP	Strong	Genetic Variation	[10]
Urinary bladder cancer	DISDV4T7	Strong	Biomarker	[3]
Urinary bladder neoplasm	DIS7HACE	Strong	Biomarker	[3]
Bacterial infection	DIS5QJ9S	moderate	Altered Expression	[17]
Chronic kidney disease	DISW82R7	moderate	Genetic Variation	[18]
Influenza	DIS3PNU3	moderate	Biomarker	[19]
Stroke	DISX6UHX	moderate	Genetic Variation	[20]
Gastric cancer	DISXGOUK	Disputed	Biomarker	[21]
Stomach cancer	DISKIJSX	Disputed	Biomarker	[21]
Breast cancer	DIS7DPX1	Limited	Altered Expression	[4]
Breast neoplasm	DISNGJLM	Limited	Altered Expression	[22]
Clear cell renal carcinoma	DISBXRFJ	Limited	Biomarker	[23]
Colorectal carcinoma	DIS5PYL0	Limited	Altered Expression	[24]
Hepatitis C virus infection	DISQ0M8R	Limited	Biomarker	[25]
Melanoma	DIS1RRCY	Limited	Altered Expression	[26]
Nasopharyngeal carcinoma	DISAOTQ0	Limited	Biomarker	[27]
Neoplasm	DISZKGEW	Limited	Biomarker	[2]

17 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 Interleukin enhancer-binding factor 3 (ILF3).	[28]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Interleukin enhancer-binding factor 3 (ILF3).	[29]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Interleukin enhancer-binding factor 3 (ILF3).	[30]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Interleukin enhancer-binding factor 3 (ILF3).	[31]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Interleukin enhancer-binding factor 3 (ILF3).	[32]
Vorinostat	DMWMPD4	Approved	Vorinostat decreases the expression of Interleukin enhancer-binding factor 3 (ILF3).	[33]
Troglitazone	DM3VFPD	Approved	Troglitazone decreases the expression of Interleukin enhancer-binding factor 3 (ILF3).	[34]
Piroxicam	DMTK234	Approved	Piroxicam decreases the expression of Interleukin enhancer-binding factor 3 (ILF3).	[35]
Tamibarotene	DM3G74J	Phase 3	Tamibarotene decreases the expression of Interleukin enhancer-binding factor 3 (ILF3).	[29]
Epigallocatechin gallate	DMCGWBJ	Phase 3	Epigallocatechin gallate increases the expression of Interleukin enhancer-binding factor 3 (ILF3).	[36]
Genistein	DM0JETC	Phase 2/3	Genistein decreases the expression of Interleukin enhancer-binding factor 3 (ILF3).	[37]
Tocopherol	DMBIJZ6	Phase 2	Tocopherol decreases the expression of Interleukin enhancer-binding factor 3 (ILF3).	[38]
NVP-AUY922	DMTYXQF	Phase 2	NVP-AUY922 decreases the expression of Interleukin enhancer-binding factor 3 (ILF3).	[40]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Interleukin enhancer-binding factor 3 (ILF3).	[43]
Torcetrapib	DMDHYM7	Discontinued in Phase 2	Torcetrapib increases the expression of Interleukin enhancer-binding factor 3 (ILF3).	[45]
SB-431542	DM0YOXQ	Preclinical	SB-431542 increases the expression of Interleukin enhancer-binding factor 3 (ILF3).	[46]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Interleukin enhancer-binding factor 3 (ILF3).	[47]

1 Drug(s) Affected the Protein Interaction/Cellular Processes of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
DNCB	DMDTVYC	Phase 2	DNCB affects the binding of Interleukin enhancer-binding factor 3 (ILF3).	[39]

4 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 Interleukin enhancer-binding factor 3 (ILF3).	[41]
TAK-243	DM4GKV2	Phase 1	TAK-243 decreases the sumoylation of Interleukin enhancer-binding factor 3 (ILF3).	[42]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 decreases the phosphorylation of Interleukin enhancer-binding factor 3 (ILF3).	[44]
Coumarin	DM0N8ZM	Investigative	Coumarin increases the phosphorylation of Interleukin enhancer-binding factor 3 (ILF3).	[44]

References

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