Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTE8FHQD)

• DOT Name: Protein ILRUN (ILRUN)
• Synonyms: Inflammation and lipid regulator with UBA-like and NBR1-like domains protein
• Gene Name: ILRUN
• Related Disease:
  Small lymphocytic lymphoma
  Advanced cancer
  Breast cancer
  Breast carcinoma
  Lung cancer
  Lung carcinoma
  Non-small-cell lung cancer
  Coronary heart disease
  Neoplasm
  Systemic lupus erythematosus
  Invasive breast carcinoma
  Invasive ductal breast carcinoma
  Triple negative breast cancer
• UniProt ID: ILRUN_HUMAN
• PDB ID: 6VHI
• Pfam ID: PF16158 ; PF14555
• Sequence:
  MEGMDVDLDPELMQKFSCLGTTDKDVLISEFQRLLGFQLNPAGCAFFLDMTNWNLQAAIG
  AYYDFESPNISVPSMSFVEDVTIGEGESIPPDTQFVKTWRIQNSGAEAWPPGVCLKYVGG
  DQFGHVNMVMVRSLEPQEIADVSVQMCSPSRAGMYQGQWRMCTATGLYYGDVIWVILSVE
  VGGLLGVTQQLSSFETEFNTQPHRKVEGNFNPFASPQKNRQSDENNLKDPGGSEFDSISK
  NTWAPAPDTWAPAPDQTEQDQNRLSQNSVNLSPSSHANNLSVVTYSKGLHGPYPFGQS
• Function: Negative regulator of innate antiviral response. Blocks IRF3-dependent cytokine production such as IFNA, IFNB and TNF. Interacts with IRF3 and inhibits IRF3 recruitment to type I IFN promoter sequences while also reducing nuclear levels of the coactivators EP300 and CREBBP.
• Tissue Specificity: Expressed in lung (at protein level).

Molecular Interaction Atlas (MIA) of This DOT

13 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Small lymphocytic lymphoma	DIS30POX	Definitive	Genetic Variation	[1]
Advanced cancer	DISAT1Z9	Strong	Altered Expression	[2]
Breast cancer	DIS7DPX1	Strong	Altered Expression	[2]
Breast carcinoma	DIS2UE88	Strong	Altered Expression	[2]
Lung cancer	DISCM4YA	Strong	Altered Expression	[3]
Lung carcinoma	DISTR26C	Strong	Altered Expression	[3]
Non-small-cell lung cancer	DIS5Y6R9	Strong	Altered Expression	[3]
Coronary heart disease	DIS5OIP1	moderate	Genetic Variation	[4]
Neoplasm	DISZKGEW	moderate	Biomarker	[2]
Systemic lupus erythematosus	DISI1SZ7	moderate	Genetic Variation	[5]
Invasive breast carcinoma	DISANYTW	Limited	Biomarker	[6]
Invasive ductal breast carcinoma	DIS43J58	Limited	Biomarker	[6]
Triple negative breast cancer	DISAMG6N	Limited	Biomarker	[6]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the expression of Protein ILRUN (ILRUN).	[7]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Protein ILRUN (ILRUN).	[8]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Protein ILRUN (ILRUN).	[9]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Protein ILRUN (ILRUN).	[10]
Vorinostat	DMWMPD4	Approved	Vorinostat decreases the expression of Protein ILRUN (ILRUN).	[11]
Selenium	DM25CGV	Approved	Selenium increases the expression of Protein ILRUN (ILRUN).	[12]
Fulvestrant	DM0YZC6	Approved	Fulvestrant decreases the expression of Protein ILRUN (ILRUN).	[10]
Afimoxifene	DMFORDT	Phase 2	Afimoxifene decreases the expression of Protein ILRUN (ILRUN).	[10]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the mutagenesis of Protein ILRUN (ILRUN).	[13]
Lithium chloride	DMHYLQ2	Investigative	Lithium chloride increases the expression of Protein ILRUN (ILRUN).	[15]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the methylation of Protein ILRUN (ILRUN).	[14]

References

• [1] Genome-wide association analysis implicates dysregulation of immunity genes in chronic lymphocytic leukaemia.Nat Commun. 2017 Feb 6;8:14175. doi: 10.1038/ncomms14175.
• [2] C6orf106 accelerates pancreatic cancer cell invasion and proliferation via activating ERK signaling pathway.Mol Cell Biochem. 2019 Apr;454(1-2):87-95. doi: 10.1007/s11010-018-3455-0. Epub 2018 Oct 11.
• [3] C6orf106 enhances NSCLC cell invasion by upregulating vimentin, and downregulating E-cadherin and P120ctn.Tumour Biol. 2015 Aug;36(8):5979-85. doi: 10.1007/s13277-015-3274-9. Epub 2015 Mar 4.
• [4] Identification of 64 Novel Genetic Loci Provides an Expanded View on the Genetic Architecture of Coronary Artery Disease.Circ Res. 2018 Feb 2;122(3):433-443. doi: 10.1161/CIRCRESAHA.117.312086. Epub 2017 Dec 6.
• [5] Meta-analysis followed by replication identifies loci in or near CDKN1B, TET3, CD80, DRAM1, and ARID5B as associated with systemic lupus erythematosus in Asians.Am J Hum Genet. 2013 Jan 10;92(1):41-51. doi: 10.1016/j.ajhg.2012.11.018. Epub 2012 Dec 27.
• [6] A novel biomarker C6orf106 promotes the malignant progression of breast cancer.Tumour Biol. 2015 Sep;36(10):7881-9. doi: 10.1007/s13277-015-3500-5. Epub 2015 May 8.
• [7] Stem cell transcriptome responses and corresponding biomarkers that indicate the transition from adaptive responses to cytotoxicity. Chem Res Toxicol. 2017 Apr 17;30(4):905-922.
• [8] Phenotypic characterization of retinoic acid differentiated SH-SY5Y cells by transcriptional profiling. PLoS One. 2013 May 28;8(5):e63862.
• [9] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [10] Comparative gene expression profiling reveals partially overlapping but distinct genomic actions of different antiestrogens in human breast cancer cells. J Cell Biochem. 2006 Aug 1;98(5):1163-84.
• [11] Definition of transcriptome-based indices for quantitative characterization of chemically disturbed stem cell development: introduction of the STOP-Toxukn and STOP-Toxukk tests. Arch Toxicol. 2017 Feb;91(2):839-864.
• [12] Selenium and vitamin E: cell type- and intervention-specific tissue effects in prostate cancer. J Natl Cancer Inst. 2009 Mar 4;101(5):306-20.
• [13] Exome-wide mutation profile in benzo[a]pyrene-derived post-stasis and immortal human mammary epithelial cells. Mutat Res Genet Toxicol Environ Mutagen. 2014 Dec;775-776:48-54. doi: 10.1016/j.mrgentox.2014.10.011. Epub 2014 Nov 4.
• [14] 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.
• [15] Effects of lithium and valproic acid on gene expression and phenotypic markers in an NT2 neurosphere model of neural development. PLoS One. 2013;8(3):e58822.