Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTVZP6YB)

• DOT Name: BolA-like protein 2 (BOLA2)
• Gene Name: BOLA2
• Related Disease:
  Advanced cancer
  Hepatocellular carcinoma
  Neoplasm
• UniProt ID: BOLA2_HUMAN
• Pfam ID: PF01722
• Sequence:
  MELSAEYLREKLQRDLEAEHVEVEDTTLNRCSCSFRVLVVSAKFEGKPLLQRHRLVNACL
  AEELPHIHAFEQKTLTPDQWARERQK
• Function: Acts as a cytosolic iron-sulfur (Fe-S) cluster assembly factor that facilitates [2Fe-2S] cluster insertion into a subset of cytosolic proteins. Acts together with the monothiol glutaredoxin GLRX3.
• Reactome Pathway: Gene and protein expression by JAK-STAT signaling after Interleukin-12 stimulation (R-HSA-8950505)

Molecular Interaction Atlas (MIA) of This DOT

3 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Advanced cancer	DISAT1Z9	Strong	Biomarker	[1]
Hepatocellular carcinoma	DIS0J828	Strong	Biomarker	[1]
Neoplasm	DISZKGEW	Strong	Altered Expression	[1]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the methylation of BolA-like protein 2 (BOLA2).	[2]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of BolA-like protein 2 (BOLA2).	[9]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A affects the methylation of BolA-like protein 2 (BOLA2).	[11]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of BolA-like protein 2 (BOLA2).	[3]
Doxorubicin	DMVP5YE	Approved	Doxorubicin increases the expression of BolA-like protein 2 (BOLA2).	[4]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of BolA-like protein 2 (BOLA2).	[5]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of BolA-like protein 2 (BOLA2).	[6]
Zoledronate	DMIXC7G	Approved	Zoledronate increases the expression of BolA-like protein 2 (BOLA2).	[7]
Amiodarone	DMUTEX3	Phase 2/3 Trial	Amiodarone increases the expression of BolA-like protein 2 (BOLA2).	[8]
UNC0379	DMD1E4J	Preclinical	UNC0379 decreases the expression of BolA-like protein 2 (BOLA2).	[10]

References

• [1] BolA family member 2 enhances cell proliferation and predicts a poor prognosis in hepatocellular carcinoma with tumor hemorrhage.J Cancer. 2019 Jul 10;10(18):4293-4304. doi: 10.7150/jca.31829. eCollection 2019.
• [2] 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.
• [3] Phenotypic characterization of retinoic acid differentiated SH-SY5Y cells by transcriptional profiling. PLoS One. 2013 May 28;8(5):e63862.
• [4] Bringing in vitro analysis closer to in vivo: studying doxorubicin toxicity and associated mechanisms in 3D human microtissues with PBPK-based dose modelling. Toxicol Lett. 2018 Sep 15;294:184-192.
• [5] 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.
• [6] Minimal peroxide exposure of neuronal cells induces multifaceted adaptive responses. PLoS One. 2010 Dec 17;5(12):e14352. doi: 10.1371/journal.pone.0014352.
• [7] Interleukin-19 as a translational indicator of renal injury. Arch Toxicol. 2015 Jan;89(1):101-6.
• [8] Identification by automated screening of a small molecule that selectively eliminates neural stem cells derived from hESCs but not dopamine neurons. PLoS One. 2009 Sep 23;4(9):e7155.
• [9] Air pollution and DNA methylation alterations in lung cancer: A systematic and comparative study. Oncotarget. 2017 Jan 3;8(1):1369-1391. doi: 10.18632/oncotarget.13622.
• [10] Epigenetic siRNA and chemical screens identify SETD8 inhibition as a therapeutic strategy for p53 activation in high-risk neuroblastoma. Cancer Cell. 2017 Jan 9;31(1):50-63.
• [11] 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.