Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTHGB81W)

• DOT Name: Protein Bop (RTL10)
• Synonyms: BH3-only protein; Retrotransposon Gag-like protein 10
• Gene Name: RTL10
• Related Disease:
  Adult glioblastoma
  Adult lymphoma
  Advanced cancer
  Autoimmune disease
  B-cell neoplasm
  Breast cancer
  Breast carcinoma
  Burkitt lymphoma
  Clear cell renal carcinoma
  Glioblastoma multiforme
  Huntington disease
  Lymphoma
  Matthew-Wood syndrome
  Melanoma
  Non-small-cell lung cancer
  Parkinson disease
  Pediatric lymphoma
  Plasma cell myeloma
  Prostate cancer
  Prostate carcinoma
  Renal cell carcinoma
  Small lymphocytic lymphoma
  Bacterial infection
  Gastritis
  Neoplasm
  Status epilepticus seizure
• UniProt ID: BOP_HUMAN
• Pfam ID: PF16297
• Sequence:
  MPRGRCRQQGPRIPIWAAANYANAHPWQQMDKASPGVAYTPLVDPWIERPCCGDTVCVRT
  TMEQKSTASGTCGGKPAERGPLAGHMPSSRPHRVDFCWVPGSDPGTFDGSPWLLDRFLAQ
  LGDYMSFHFEHYQDNISRVCEILRRLTGRAQAWAAPYLDGDLPLPDDYELFCQDLKEVVQ
  DPNSFAEYHAVVTCPLPLASSQLPVAPQLPVVRQYLARFLEGLALDMGTAPRSLPAAMAT
  PAVSGSNSVSRSALFEQQLTKESTPGPKEPPVLPSSTCSSKPGPVEPASSQPEEAAPTPV
  PRLSESANPPAQRPDPAHPGGPKPQKTEEEVLETEGDQEVSLGTPQEVVEAPETPGEPPL
  SPGF
• Function: Could induce apoptosis in a BH3 domain-dependent manner. The direct interaction network of Bcl-2 family members may play a key role in modulation RTL10/BOP intrinsic apoptotic signaling activity.
• Tissue Specificity: Ubiquitously expressed.

Molecular Interaction Atlas (MIA) of This DOT

26 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Adult glioblastoma	DISVP4LU	Strong	Altered Expression	[1]
Adult lymphoma	DISK8IZR	Strong	Biomarker	[2]
Advanced cancer	DISAT1Z9	Strong	Biomarker	[3]
Autoimmune disease	DISORMTM	Strong	Biomarker	[4]
B-cell neoplasm	DISVY326	Strong	Biomarker	[5]
Breast cancer	DIS7DPX1	Strong	Biomarker	[6]
Breast carcinoma	DIS2UE88	Strong	Biomarker	[6]
Burkitt lymphoma	DIS9D5XU	Strong	Biomarker	[7]
Clear cell renal carcinoma	DISBXRFJ	Strong	Genetic Variation	[3]
Glioblastoma multiforme	DISK8246	Strong	Altered Expression	[1]
Huntington disease	DISQPLA4	Strong	Altered Expression	[8]
Lymphoma	DISN6V4S	Strong	Biomarker	[2]
Matthew-Wood syndrome	DISA7HR7	Strong	Altered Expression	[9]
Melanoma	DIS1RRCY	Strong	Biomarker	[10]
Non-small-cell lung cancer	DIS5Y6R9	Strong	Altered Expression	[11]
Parkinson disease	DISQVHKL	Strong	Biomarker	[12]
Pediatric lymphoma	DIS51BK2	Strong	Biomarker	[2]
Plasma cell myeloma	DIS0DFZ0	Strong	Altered Expression	[13]
Prostate cancer	DISF190Y	Strong	Biomarker	[14]
Prostate carcinoma	DISMJPLE	Strong	Biomarker	[14]
Renal cell carcinoma	DISQZ2X8	Strong	Biomarker	[3]
Small lymphocytic lymphoma	DIS30POX	Strong	Biomarker	[15]
Bacterial infection	DIS5QJ9S	moderate	Biomarker	[16]
Gastritis	DIS8G07K	moderate	Biomarker	[17]
Neoplasm	DISZKGEW	moderate	Biomarker	[18]
Status epilepticus seizure	DISY3BIC	Limited	Genetic Variation	[19]

12 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 Protein Bop (RTL10).	[20]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Protein Bop (RTL10).	[21]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Protein Bop (RTL10).	[22]
Arsenic	DMTL2Y1	Approved	Arsenic decreases the expression of Protein Bop (RTL10).	[23]
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of Protein Bop (RTL10).	[24]
Testosterone	DM7HUNW	Approved	Testosterone decreases the expression of Protein Bop (RTL10).	[25]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Protein Bop (RTL10).	[26]
Resveratrol	DM3RWXL	Phase 3	Resveratrol increases the expression of Protein Bop (RTL10).	[27]
Genistein	DM0JETC	Phase 2/3	Genistein increases the expression of Protein Bop (RTL10).	[27]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Protein Bop (RTL10).	[27]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of Protein Bop (RTL10).	[28]
Sulforaphane	DMQY3L0	Investigative	Sulforaphane decreases the expression of Protein Bop (RTL10).	[29]

References

• [1] Lovastatin-induced up-regulation of the BH3-only protein, Bim, and cell death in glioblastoma cells.J Neurochem. 2004 Apr;89(1):168-78. doi: 10.1111/j.1471-4159.2004.02319.x.
• [2] Combined inhibition of PI3K-related DNA damage response kinases and mTORC1 induces apoptosis in MYC-driven B-cell lymphomas.Blood. 2013 Apr 11;121(15):2964-74. doi: 10.1182/blood-2012-08-446096. Epub 2013 Feb 12.
• [3] Loss of the tissue-specific proapoptotic BH3-only protein Nbk/Bik is a unifying feature of renal cell carcinoma.Cell Death Differ. 2006 Apr;13(4):619-27. doi: 10.1038/sj.cdd.4401782.
• [4] The pro-apoptotic protein Bmf co-operates with Bim and Puma in neuron death induced by -amyloid or NGF deprivation.Mol Cell Neurosci. 2018 Apr;88:249-257. doi: 10.1016/j.mcn.2018.02.011. Epub 2018 Feb 27.
• [5] Apoptosis and autophagy: BIM as a mediator of tumour cell death in response to oncogene-targeted therapeutics.FEBS J. 2009 Nov;276(21):6050-62. doi: 10.1111/j.1742-4658.2009.07329.x. Epub 2009 Sep 29.
• [6] The pro-apoptotic paradox: the BH3-only protein Bcl-2 interacting killer (Bik) is prognostic for unfavorable outcomes in breast cancer.Oncotarget. 2016 May 31;7(22):33272-85. doi: 10.18632/oncotarget.8924.
• [7] TGFbeta-mediated apoptosis of Burkitt's lymphoma BL41 cells is associated with the relocation of mitochondrial BimEL.Oncogene. 2008 May 29;27(24):3446-56. doi: 10.1038/sj.onc.1211009. Epub 2008 Jan 14.
• [8] Bim contributes to the progression of Huntington's disease-associated phenotypes.Hum Mol Genet. 2020 Jan 15;29(2):216-227. doi: 10.1093/hmg/ddz275.
• [9] HDAC2 mediates therapeutic resistance of pancreatic cancer cells via the BH3-only protein NOXA.Gut. 2009 Oct;58(10):1399-409. doi: 10.1136/gut.2009.180711. Epub 2009 Jun 14.
• [10] BH3-only protein silencing contributes to acquired resistance to PLX4720 in human melanoma.Cell Death Differ. 2012 Dec;19(12):2029-39. doi: 10.1038/cdd.2012.94. Epub 2012 Aug 3.
• [11] Alternative splicing of S6K1 promotes non-small cell lung cancer survival.Tumour Biol. 2016 Oct;37(10):13369-13376. doi: 10.1007/s13277-016-5253-1. Epub 2016 Jul 27.
• [12] c-Jun/Bim Upregulation in Dopaminergic Neurons Promotes Neurodegeneration in the MPTP Mouse Model of Parkinson's Disease.Neuroscience. 2019 Feb 10;399:117-124. doi: 10.1016/j.neuroscience.2018.12.026. Epub 2018 Dec 25.
• [13] Multiple myeloma cells' capacity to decompose H(2)O(2) determines lenalidomide sensitivity.Blood. 2017 Feb 23;129(8):991-1007. doi: 10.1182/blood-2016-09-738872. Epub 2016 Dec 27.
• [14] P53 enhances apoptosis induced by doxorubicin only under conditions of severe DNA damage.Cell Cycle. 2018;17(17):2175-2186. doi: 10.1080/15384101.2018.1520565. Epub 2018 Sep 22.
• [15] Hyperforin induces apoptosis of chronic lymphocytic leukemia cells through upregulation of the BH3-only protein Noxa.Int J Oncol. 2012 Jan;40(1):269-76. doi: 10.3892/ijo.2011.1206. Epub 2011 Sep 22.
• [16] Loss of BID Delays FASL-Induced Cell Death of Mouse Neutrophils and Aggravates DSS-Induced Weight Loss.Int J Mol Sci. 2018 Feb 28;19(3):684. doi: 10.3390/ijms19030684.
• [17] BH3-only protein Bim is associated with the degree of Helicobacter pylori-induced gastritis and is localized to the mitochondria of inflammatory cells in the gastric mucosa.Int J Med Microbiol. 2015 Sep;305(6):553-62. doi: 10.1016/j.ijmm.2015.07.002. Epub 2015 Jul 9.
• [18] PIDDosome-independent tumor suppression by Caspase-2.Cell Death Differ. 2012 Oct;19(10):1722-32. doi: 10.1038/cdd.2012.54. Epub 2012 May 18.
• [19] Deletion of the BH3-only protein Noxa alters electrographic seizures but does not protect against hippocampal damage after status epilepticus in mice.Cell Death Dis. 2017 Jan 12;8(1):e2556. doi: 10.1038/cddis.2016.301.
• [20] 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.
• [21] 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.
• [22] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [23] Arsenic alters transcriptional responses to Pseudomonas aeruginosa infection and decreases antimicrobial defense of human airway epithelial cells. Toxicol Appl Pharmacol. 2017 Sep 15;331:154-163.
• [24] Large-scale in silico and microarray-based identification of direct 1,25-dihydroxyvitamin D3 target genes. Mol Endocrinol. 2005 Nov;19(11):2685-95.
• [25] The exosome-like vesicles derived from androgen exposed-prostate stromal cells promote epithelial cells proliferation and epithelial-mesenchymal transition. Toxicol Appl Pharmacol. 2021 Jan 15;411:115384. doi: 10.1016/j.taap.2020.115384. Epub 2020 Dec 25.
• [26] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [27] Gene expression profiling in Ishikawa cells: a fingerprint for estrogen active compounds. Toxicol Appl Pharmacol. 2009 Apr 1;236(1):85-96.
• [28] Gene expression changes in primary human nasal epithelial cells exposed to formaldehyde in vitro. Toxicol Lett. 2010 Oct 5;198(2):289-95.
• [29] Transcriptome and DNA methylation changes modulated by sulforaphane induce cell cycle arrest, apoptosis, DNA damage, and suppression of proliferation in human liver cancer cells. Food Chem Toxicol. 2020 Feb;136:111047. doi: 10.1016/j.fct.2019.111047. Epub 2019 Dec 12.