Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTWWVM9X)

• DOT Name: Interleukin enhancer-binding factor 2 (ILF2)
• Synonyms: Nuclear factor of activated T-cells 45 kDa
• Gene Name: ILF2
• Related Disease:
  Neurodevelopmental disorder
  Advanced cancer
  B-cell neoplasm
  Brain disease
  Breast cancer
  Breast carcinoma
  Carcinoma of liver and intrahepatic biliary tract
  Dengue
  Esophageal squamous cell carcinoma
  Glioma
  Hepatitis C virus infection
  Hepatocellular carcinoma
  Lentivirus infection
  Liver cancer
  Lung neoplasm
  Nervous system disease
  Non-small-cell lung cancer
  Plasma cell myeloma
  Sjogren syndrome
  Bacterial infection
  Cervical carcinoma
  Gastric cancer
  Gonorrhea
  HIV infectious disease
  Matthew-Wood syndrome
  Neoplasm
  Pancreatic cancer
  Pancreatic ductal carcinoma
  Stomach cancer
  Nasopharyngeal carcinoma
• UniProt ID: ILF2_HUMAN
• Pfam ID: PF20965 ; PF07528
• Sequence:
  MRGDRGRGRGGRFGSRGGPGGGFRPFVPHIPFDFYLCEMAFPRVKPAPDETSFSEALLKR
  NQDLAPNSAEQASILSLVTKINNVIDNLIVAPGTFEVQIEEVRQVGSYKKGTMTTGHNVA
  DLVVILKILPTLEAVAALGNKVVESLRAQDPSEVLTMLTNETGFEISSSDATVKILITTV
  PPNLRKLDPELHLDIKVLQSALAAIRHARWFEENASQSTVKVLIRLLKDLRIRFPGFEPL
  TPWILDLLGHYAVMNNPTRQPLALNVAYRRCLQILAAGLFLPGSVGITDPCESGNFRVHT
  VMTLEQQDMVCYTAQTLVRILSHGGFRKILGQEGDASYLASEISTWDGVIVTPSEKAYEK
  PPEKKEGEEEEENTEEPPQGEEEESMETQE
• Function: Chromatin-interacting protein that forms a stable heterodimer with interleukin enhancer-binding factor 3/ILF3 and plays a role in several biological processes including transcription, innate immunity or cell growth. Essential for the efficient reshuttling of ILF3 (isoform 1 and isoform 2) into the nucleus. Together with ILF3, forms an RNA-binding complex that is required for mitotic progression and cytokinesis by regulating the expression of a cluster of mitotic genes. Mechanistically, competes with STAU1/STAU2-mediated mRNA decay. Also plays a role in the inhibition of various viruses including Japanese encephalitis virus or enterovirus 71; (Microbial infection) Plays a positive role in HIV-1 virus production by binding to and thereby stabilizing HIV-1 RNA, together with ILF3.
• Reactome Pathway:
  PKR-mediated signaling (R-HSA-9833482)
  Neutrophil degranulation (R-HSA-6798695)

Molecular Interaction Atlas (MIA) of This DOT

30 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Neurodevelopmental disorder	DIS372XH	Definitive	Biomarker	[1]
Advanced cancer	DISAT1Z9	Strong	Altered Expression	[2]
B-cell neoplasm	DISVY326	Strong	Altered Expression	[3]
Brain disease	DIS6ZC3X	Strong	Biomarker	[4]
Breast cancer	DIS7DPX1	Strong	Altered Expression	[2]
Breast carcinoma	DIS2UE88	Strong	Altered Expression	[2]
Carcinoma of liver and intrahepatic biliary tract	DIS8WA0W	Strong	Biomarker	[5]
Dengue	DISKH221	Strong	Biomarker	[6]
Esophageal squamous cell carcinoma	DIS5N2GV	Strong	Altered Expression	[7]
Glioma	DIS5RPEH	Strong	Biomarker	[8]
Hepatitis C virus infection	DISQ0M8R	Strong	Biomarker	[9]
Hepatocellular carcinoma	DIS0J828	Strong	Biomarker	[10]
Lentivirus infection	DISX17PY	Strong	Biomarker	[11]
Liver cancer	DISDE4BI	Strong	Biomarker	[5]
Lung neoplasm	DISVARNB	Strong	Biomarker	[12]
Nervous system disease	DISJ7GGT	Strong	Biomarker	[4]
Non-small-cell lung cancer	DIS5Y6R9	Strong	Altered Expression	[8]
Plasma cell myeloma	DIS0DFZ0	Strong	Biomarker	[13]
Sjogren syndrome	DISUBX7H	Strong	Biomarker	[14]
Bacterial infection	DIS5QJ9S	moderate	Biomarker	[15]
Cervical carcinoma	DIST4S00	moderate	Biomarker	[16]
Gastric cancer	DISXGOUK	moderate	Biomarker	[17]
Gonorrhea	DISQ5AO6	moderate	Biomarker	[17]
HIV infectious disease	DISO97HC	moderate	Biomarker	[18]
Matthew-Wood syndrome	DISA7HR7	moderate	Altered Expression	[19]
Neoplasm	DISZKGEW	moderate	Altered Expression	[8]
Pancreatic cancer	DISJC981	moderate	Biomarker	[20]
Pancreatic ductal carcinoma	DIS26F9Q	moderate	Altered Expression	[19]
Stomach cancer	DISKIJSX	moderate	Biomarker	[17]
Nasopharyngeal carcinoma	DISAOTQ0	Limited	Biomarker	[21]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Interleukin enhancer-binding factor 2 (ILF2).	[22]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Interleukin enhancer-binding factor 2 (ILF2).	[23]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Interleukin enhancer-binding factor 2 (ILF2).	[24]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Interleukin enhancer-binding factor 2 (ILF2).	[25]
Menadione	DMSJDTY	Approved	Menadione affects the expression of Interleukin enhancer-binding factor 2 (ILF2).	[26]
Epigallocatechin gallate	DMCGWBJ	Phase 3	Epigallocatechin gallate decreases the expression of Interleukin enhancer-binding factor 2 (ILF2).	[27]
Genistein	DM0JETC	Phase 2/3	Genistein increases the expression of Interleukin enhancer-binding factor 2 (ILF2).	[24]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Interleukin enhancer-binding factor 2 (ILF2).	[29]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Interleukin enhancer-binding factor 2 (ILF2).	[30]
Coumestrol	DM40TBU	Investigative	Coumestrol increases the expression of Interleukin enhancer-binding factor 2 (ILF2).	[31]
chloropicrin	DMSGBQA	Investigative	chloropicrin increases the expression of Interleukin enhancer-binding factor 2 (ILF2).	[32]
geraniol	DMS3CBD	Investigative	geraniol decreases the expression of Interleukin enhancer-binding factor 2 (ILF2).	[33]
AHPN	DM8G6O4	Investigative	AHPN decreases the expression of Interleukin enhancer-binding factor 2 (ILF2).	[34]
Paraoxon	DMN4ZKC	Investigative	Paraoxon increases the expression of Interleukin enhancer-binding factor 2 (ILF2).	[35]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
TAK-243	DM4GKV2	Phase 1	TAK-243 increases the sumoylation of Interleukin enhancer-binding factor 2 (ILF2).	[28]

References

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• [11] Interleukin-enhanced binding factor 2 interacts with NLRP3 to inhibit the NLRP3 inflammasome activation.Biochem Biophys Res Commun. 2018 Jun 2;500(2):398-404. doi: 10.1016/j.bbrc.2018.04.087. Epub 2018 Apr 14.
• [12] PRMT6 Promotes Lung Tumor Progression via the Alternate Activation of Tumor-Associated Macrophages.Mol Cancer Res. 2020 Jan;18(1):166-178. doi: 10.1158/1541-7786.MCR-19-0204. Epub 2019 Oct 16.
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• [17] Expression and Clinical Significance of ILF2 in Gastric Cancer.Dis Markers. 2017;2017:4387081. doi: 10.1155/2017/4387081. Epub 2017 Jul 31.
• [18] NF45 and NF90 Bind HIV-1 RNA and Modulate HIV Gene Expression.Viruses. 2016 Feb 16;8(2):47. doi: 10.3390/v8020047.
• [19] NF45 overexpression is associated with poor prognosis and enhanced cell proliferation of pancreatic ductal adenocarcinoma.Mol Cell Biochem. 2015 Dec;410(1-2):25-35. doi: 10.1007/s11010-015-2535-7. Epub 2015 Aug 15.
• [20] MicroRNA-7 functions as a tumor-suppressor gene by regulating ILF2 in pancreatic carcinoma.Int J Mol Med. 2017 Apr;39(4):900-906. doi: 10.3892/ijmm.2017.2894. Epub 2017 Feb 17.
• [21] Long non-coding RNA DANCR stabilizes HIF-1 and promotes metastasis by interacting with NF90/NF45 complex in nasopharyngeal carcinoma.Theranostics. 2018 Nov 10;8(20):5676-5689. doi: 10.7150/thno.28538. eCollection 2018.
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• [23] Transcriptional and Metabolic Dissection of ATRA-Induced Granulocytic Differentiation in NB4 Acute Promyelocytic Leukemia Cells. Cells. 2020 Nov 5;9(11):2423. doi: 10.3390/cells9112423.
• [24] Convergent transcriptional profiles induced by endogenous estrogen and distinct xenoestrogens in breast cancer cells. Carcinogenesis. 2006 Aug;27(8):1567-78.
• [25] Quantitative proteomics reveals a broad-spectrum antiviral property of ivermectin, benefiting for COVID-19 treatment. J Cell Physiol. 2021 Apr;236(4):2959-2975. doi: 10.1002/jcp.30055. Epub 2020 Sep 22.
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• [33] Geraniol suppresses prostate cancer growth through down-regulation of E2F8. Cancer Med. 2016 Oct;5(10):2899-2908.
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• [35] Paraoxon-induced protein expression changes to SH-SY5Y cells. Chem Res Toxicol. 2010 Nov 15;23(11):1656-62. doi: 10.1021/tx100192f. Epub 2010 Oct 8.