Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTSHV8JF)

• DOT Name: INO80 complex subunit B (INO80B)
• Synonyms: High mobility group AT-hook 1-like 4; IES2 homolog; hIes2; PAP-1-associated protein 1; PAPA-1; Zinc finger HIT domain-containing protein 4
• Gene Name: INO80B
• Related Disease:
  Eclampsia
  Lung cancer
  Lung carcinoma
  Prostate cancer
  Prostate carcinoma
  Tuberculosis
• UniProt ID: IN80B_HUMAN
• PDB ID: 6HTS; 7ZI4
• Pfam ID: PF04795 ; PF04438
• Sequence:
  MSKLWRRGSTSGAMEAPEPGEALELSLAGAHGHGVHKKKHKKHKKKHKKKHHQEEDAGPT
  QPSPAKPQLKLKIKLGGQVLGTKSVPTFTVIPEGPRSPSPLMVVDNEEEPMEGVPLEQYR
  AWLDEDSNLSPSPLRDLSGGLGGQEEEEEQRWLDALEKGELDDNGDLKKEINERLLTARQ
  RALLQKARSQPSPMLPLPVAEGCPPPALTEEMLLKREERARKRRLQAARRAEEHKNQTIE
  RLTKTAATSGRGGRGGARGERRGGRAAAPAPMVRYCSGAQGSTLSFPPGVPAPTAVSQRP
  SPSGPPPRCSVPGCPHPRRYACSRTGQALCSLQCYRINLQMRLGGPEGPGSPLLAT
• Function: Induces growth and cell cycle arrests at the G1 phase of the cell cycle; Proposed core component of the chromatin remodeling INO80 complex which is involved in transcriptional regulation, DNA replication and probably DNA repair.
• KEGG Pathway: ATP-dependent chromatin remodeling (hsa03082)
• Reactome Pathway:
  DNA Damage Recognition in GG-NER (R-HSA-5696394)
  UCH proteinases (R-HSA-5689603)

Molecular Interaction Atlas (MIA) of This DOT

6 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Eclampsia	DISWPO8U	Strong	Genetic Variation	[1]
Lung cancer	DISCM4YA	Strong	Biomarker	[2]
Lung carcinoma	DISTR26C	Strong	Biomarker	[2]
Prostate cancer	DISF190Y	Strong	Biomarker	[3]
Prostate carcinoma	DISMJPLE	Strong	Biomarker	[3]
Tuberculosis	DIS2YIMD	Strong	Altered Expression	[4]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate affects the expression of INO80 complex subunit B (INO80B).	[5]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of INO80 complex subunit B (INO80B).	[6]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of INO80 complex subunit B (INO80B).	[7]
Quercetin	DM3NC4M	Approved	Quercetin increases the expression of INO80 complex subunit B (INO80B).	[8]
Bortezomib	DMNO38U	Approved	Bortezomib decreases the expression of INO80 complex subunit B (INO80B).	[9]
Amphotericin B	DMTAJQE	Approved	Amphotericin B decreases the expression of INO80 complex subunit B (INO80B).	[10]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of INO80 complex subunit B (INO80B).	[8]
AHPN	DM8G6O4	Investigative	AHPN decreases the expression of INO80 complex subunit B (INO80B).	[12]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 increases the phosphorylation of INO80 complex subunit B (INO80B).	[11]

References

• [1] Susceptibility allele-specific loss of miR-1324-mediated silencing of the INO80B chromatin-assembly complex gene in pre-eclampsia.Hum Mol Genet. 2015 Jan 1;24(1):118-27. doi: 10.1093/hmg/ddu423. Epub 2014 Aug 20.
• [2] INO80 is required for oncogenic transcription and tumor growth in non-small cell lung cancer.Oncogene. 2017 Mar;36(10):1430-1439. doi: 10.1038/onc.2016.311. Epub 2016 Sep 19.
• [3] PAPA-1 Is a nuclear binding partner of IGFBP-2 and modulates its growth-promoting actions.Mol Endocrinol. 2009 Feb;23(2):169-75. doi: 10.1210/me.2008-0168. Epub 2008 Dec 18.
• [4] Genome-wide DNA methylation and transcriptome and proteome changes in Mycobacterium tuberculosis with para-aminosalicylic acid resistance.Chem Biol Drug Des. 2020 Jan;95(1):104-112. doi: 10.1111/cbdd.13625. Epub 2019 Nov 7.
• [5] Gene Expression Regulation and Pathway Analysis After Valproic Acid and Carbamazepine Exposure in a Human Embryonic Stem Cell-Based Neurodevelopmental Toxicity Assay. Toxicol Sci. 2015 Aug;146(2):311-20. doi: 10.1093/toxsci/kfv094. Epub 2015 May 15.
• [6] Comparison of HepG2 and HepaRG by whole-genome gene expression analysis for the purpose of chemical hazard identification. Toxicol Sci. 2010 May;115(1):66-79.
• [7] Comparative Analysis of Transcriptomic Changes including mRNA and microRNA Expression Induced by the Xenoestrogens Zearalenone and Bisphenol A in Human Ovarian Cells. Toxins (Basel). 2023 Feb 9;15(2):140. doi: 10.3390/toxins15020140.
• [8] Comparison of phenotypic and transcriptomic effects of false-positive genotoxins, true genotoxins and non-genotoxins using HepG2 cells. Mutagenesis. 2011 Sep;26(5):593-604.
• [9] The proapoptotic effect of zoledronic acid is independent of either the bone microenvironment or the intrinsic resistance to bortezomib of myeloma cells and is enhanced by the combination with arsenic trioxide. Exp Hematol. 2011 Jan;39(1):55-65.
• [10] Differential expression of microRNAs and their predicted targets in renal cells exposed to amphotericin B and its complex with copper (II) ions. Toxicol Mech Methods. 2017 Sep;27(7):537-543. doi: 10.1080/15376516.2017.1333554. Epub 2017 Jun 8.
• [11] 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.
• [12] ST1926, a novel and orally active retinoid-related molecule inducing apoptosis in myeloid leukemia cells: modulation of intracellular calcium homeostasis. Blood. 2004 Jan 1;103(1):194-207.