Details of Drug Off-Target (DOT)

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

• DOT Name: Protein Niban 2 (NIBAN2)
• Synonyms: Meg-3; Melanoma invasion by ERK; MINERVA; Niban-like protein 1; Protein FAM129B
• Gene Name: NIBAN2
• Related Disease:
  Advanced cancer
  Stomach cancer
  Atrial fibrillation
  Breast cancer
  Breast carcinoma
  Colon cancer
  Colon carcinoma
  Glioma
  Lung cancer
  Lung carcinoma
  Cardiovascular disease
  Pancreatic cancer
  Neoplasm
  Adult glioblastoma
  Glioblastoma multiforme
  Hepatocellular carcinoma
• UniProt ID: NIBA2_HUMAN
• PDB ID: 7CTP
• Sequence:
  MGDVLSTHLDDARRQHIAEKTGKILTEFLQFYEDQYGVALFNSMRHEIEGTGLPQAQLLW
  RKVPLDERIVFSGNLFQHQEDSKKWRNRFSLVPHNYGLVLYENKAAYERQVPPRAVINSA
  GYKILTSVDQYLELIGNSLPGTTAKSGSAPILKCPTQFPLILWHPYARHYYFCMMTEAEQ
  DKWQAVLQDCIRHCNNGIPEDSKVEGPAFTDAIRMYRQSKELYGTWEMLCGNEVQILSNL
  VMEELGPELKAELGPRLKGKPQERQRQWIQISDAVYHMVYEQAKARFEEVLSKVQQVQPA
  MQAVIRTDMDQIITSKEHLASKIRAFILPKAEVCVRNHVQPYIPSILEALMVPTSQGFTE
  VRDVFFKEVTDMNLNVINEGGIDKLGEYMEKLSRLAYHPLKMQSCYEKMESLRLDGLQQR
  FDVSSTSVFKQRAQIHMREQMDNAVYTFETLLHQELGKGPTKEELCKSIQRVLERVLKKY
  DYDSSSVRKRFFREALLQISIPFLLKKLAPTCKSELPRFQELIFEDFARFILVENTYEEV
  VLQTVMKDILQAVKEAAVQRKHNLYRDSMVMHNSDPNLHLLAEGAPIDWGEEYSNSGGGG
  SPSPSTPESATLSEKRRRAKQVVSVVQDEEVGLPFEASPESPPPASPDGVTEIRGLLAQG
  LRPESPPPAGPLLNGAPAGESPQPKAAPEASSPPASPLQHLLPGKAVDLGPPKPSDQETG
  EQVSSPSSHPALHTTTEDSAGVQTEF
• Function: May play a role in apoptosis suppression. May promote melanoma cell invasion in vitro.

Molecular Interaction Atlas (MIA) of This DOT

16 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Advanced cancer	DISAT1Z9	Definitive	Altered Expression	[1]
Stomach cancer	DISKIJSX	Definitive	Biomarker	[2]
Atrial fibrillation	DIS15W6U	Strong	Biomarker	[3]
Breast cancer	DIS7DPX1	Strong	Biomarker	[1]
Breast carcinoma	DIS2UE88	Strong	Biomarker	[1]
Colon cancer	DISVC52G	Strong	Biomarker	[1]
Colon carcinoma	DISJYKUO	Strong	Biomarker	[1]
Glioma	DIS5RPEH	Strong	Biomarker	[4]
Lung cancer	DISCM4YA	Strong	Biomarker	[1]
Lung carcinoma	DISTR26C	Strong	Biomarker	[1]
Cardiovascular disease	DIS2IQDX	moderate	Biomarker	[5]
Pancreatic cancer	DISJC981	moderate	Biomarker	[6]
Neoplasm	DISZKGEW	Disputed	Altered Expression	[7]
Adult glioblastoma	DISVP4LU	Limited	Biomarker	[8]
Glioblastoma multiforme	DISK8246	Limited	Biomarker	[8]
Hepatocellular carcinoma	DIS0J828	Limited	Altered Expression	[9]

10 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 Protein Niban 2 (NIBAN2).	[10]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Protein Niban 2 (NIBAN2).	[11]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Protein Niban 2 (NIBAN2).	[12]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Protein Niban 2 (NIBAN2).	[13]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Protein Niban 2 (NIBAN2).	[14]
Diethylstilbestrol	DMN3UXQ	Approved	Diethylstilbestrol decreases the expression of Protein Niban 2 (NIBAN2).	[16]
Cytarabine	DMZD5QR	Approved	Cytarabine decreases the expression of Protein Niban 2 (NIBAN2).	[17]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Protein Niban 2 (NIBAN2).	[18]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Protein Niban 2 (NIBAN2).	[21]
Milchsaure	DM462BT	Investigative	Milchsaure increases the expression of Protein Niban 2 (NIBAN2).	[22]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of Protein Niban 2 (NIBAN2).	[15]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 increases the phosphorylation of Protein Niban 2 (NIBAN2).	[19]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Protein Niban 2 (NIBAN2).	[20]

References

• [1] FAM129B, an antioxidative protein, reduces chemosensitivity by competing with Nrf2 for Keap1 binding.EBioMedicine. 2019 Jul;45:25-38. doi: 10.1016/j.ebiom.2019.06.022. Epub 2019 Jun 28.
• [2] Long noncoding RNA MEG? suppresses gastric carcinoma cell growth, invasion and migration via EMT regulation.Mol Med Rep. 2019 Sep;20(3):2685-2693. doi: 10.3892/mmr.2019.10515. Epub 2019 Jul 23.
• [3] Health care cost analysis of enhanced pacing modalities in bradycardia patients: Portuguese case study on the results of the MINERVA trial.Rev Port Cardiol (Engl Ed). 2018 Dec;37(12):973-978. doi: 10.1016/j.repc.2018.01.013. Epub 2018 Dec 7.
• [4] Tunicamycin inhibits progression of glioma cells through downregulation of the MEG-3-regulated wnt/-catenin signaling pathway.Oncol Lett. 2018 Jun;15(6):8470-8476. doi: 10.3892/ol.2018.8416. Epub 2018 Apr 3.
• [5] Kidney function, proteinuria and breast arterial calcification in women without clinical cardiovascular disease: The MINERVA study.PLoS One. 2019 Jan 17;14(1):e0210973. doi: 10.1371/journal.pone.0210973. eCollection 2019.
• [6] lncRNA MEG3 had anti-cancer effects to suppress pancreatic cancer activity.Biomed Pharmacother. 2017 May;89:1269-1276. doi: 10.1016/j.biopha.2017.02.041. Epub 2017 Mar 17.
• [7] Anti-cancer activities of Bharangin against breast cancer: Evidence for the role of NF-B and lncRNAs.Biochim Biophys Acta Gen Subj. 2018 Dec;1862(12):2738-2749. doi: 10.1016/j.bbagen.2018.08.016. Epub 2018 Aug 24.
• [8] MEG-3-mediated Wnt/-catenin signaling pathway controls the inhibition of tunicamycin-mediated viability in glioblastoma.Oncol Lett. 2018 Sep;16(3):2797-2804. doi: 10.3892/ol.2018.9048. Epub 2018 Jun 28.
• [9] lncRNA involvement in hepatocellular carcinoma metastasis and prognosis.EXCLI J. 2018 Sep 4;17:900-913. doi: 10.17179/excli2018-1541. eCollection 2018.
• [10] 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.
• [11] 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.
• [12] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [13] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [14] 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.
• [15] 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.
• [16] Gene expression profiling in Ishikawa cells: a fingerprint for estrogen active compounds. Toxicol Appl Pharmacol. 2009 Apr 1;236(1):85-96.
• [17] Cytosine arabinoside induces ectoderm and inhibits mesoderm expression in human embryonic stem cells during multilineage differentiation. Br J Pharmacol. 2011 Apr;162(8):1743-56.
• [18] Cell-based two-dimensional morphological assessment system to predict cancer drug-induced cardiotoxicity using human induced pluripotent stem cell-derived cardiomyocytes. Toxicol Appl Pharmacol. 2019 Nov 15;383:114761. doi: 10.1016/j.taap.2019.114761. Epub 2019 Sep 15.
• [19] 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.
• [20] 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.
• [21] 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.
• [22] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.