Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTGK4G35)

• DOT Name: Uncharacterized protein C6orf62 (C6ORF62)
• Synonyms: HBV X-transactivated gene 12 protein; HBV XAg-transactivated protein 12
• Gene Name: C6ORF62
• UniProt ID: CF062_HUMAN
• Pfam ID: PF15130
• Sequence:
  MGDPNSRKKQALNRLRAQLRKKKESLADQFDFKMYIAFVFKEKKKKSALFEVSEVIPVMT
  NNYEENILKGVRDSSYSLESSLELLQKDVVQLHAPRYQSMRRDVIGCTQEMDFILWPRND
  IEKIVCLLFSRWKESDEPFRPVQAKFEFHHGDYEKQFLHVLSRKDKTGIVVNNPNQSVFL
  FIDRQHLQTPKNKATIFKLCSICLYLPQEQLTHWAVGTIEDHLRPYMPE

Molecular Interaction Atlas (MIA) of This DOT

15 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 Uncharacterized protein C6orf62 (C6ORF62).	[1]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Uncharacterized protein C6orf62 (C6ORF62).	[2]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Uncharacterized protein C6orf62 (C6ORF62).	[3]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Uncharacterized protein C6orf62 (C6ORF62).	[4]
Arsenic	DMTL2Y1	Approved	Arsenic affects the expression of Uncharacterized protein C6orf62 (C6ORF62).	[5]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of Uncharacterized protein C6orf62 (C6ORF62).	[6]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide decreases the expression of Uncharacterized protein C6orf62 (C6ORF62).	[7]
Menadione	DMSJDTY	Approved	Menadione affects the expression of Uncharacterized protein C6orf62 (C6ORF62).	[8]
Bortezomib	DMNO38U	Approved	Bortezomib increases the expression of Uncharacterized protein C6orf62 (C6ORF62).	[9]
Azacitidine	DMTA5OE	Approved	Azacitidine increases the expression of Uncharacterized protein C6orf62 (C6ORF62).	[10]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of Uncharacterized protein C6orf62 (C6ORF62).	[11]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide decreases the expression of Uncharacterized protein C6orf62 (C6ORF62).	[13]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Uncharacterized protein C6orf62 (C6ORF62).	[14]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of Uncharacterized protein C6orf62 (C6ORF62).	[16]
Milchsaure	DM462BT	Investigative	Milchsaure increases the expression of Uncharacterized protein C6orf62 (C6ORF62).	[17]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of Uncharacterized protein C6orf62 (C6ORF62).	[12]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the methylation of Uncharacterized protein C6orf62 (C6ORF62).	[15]

References

• [1] 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.
• [2] 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.
• [3] Transcriptional and Metabolic Dissection of ATRA-Induced Granulocytic Differentiation in NB4 Acute Promyelocytic Leukemia Cells. Cells. 2020 Nov 5;9(11):2423. doi: 10.3390/cells9112423.
• [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] Drinking-water arsenic exposure modulates gene expression in human lymphocytes from a U.S. population. Environ Health Perspect. 2008 Apr;116(4):524-31. doi: 10.1289/ehp.10861.
• [6] Temozolomide induces activation of Wnt/-catenin signaling in glioma cells via PI3K/Akt pathway: implications in glioma therapy. Cell Biol Toxicol. 2020 Jun;36(3):273-278. doi: 10.1007/s10565-019-09502-7. Epub 2019 Nov 22.
• [7] Oxidative stress modulates theophylline effects on steroid responsiveness. Biochem Biophys Res Commun. 2008 Dec 19;377(3):797-802.
• [8] Time series analysis of oxidative stress response patterns in HepG2: a toxicogenomics approach. Toxicology. 2013 Apr 5;306:24-34.
• [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] The DNA methyltransferase inhibitors azacitidine, decitabine and zebularine exert differential effects on cancer gene expression in acute myeloid leukemia cells. Leukemia. 2009 Jun;23(6):1019-28.
• [11] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [12] 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.
• [13] Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
• [14] 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.
• [15] 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.
• [16] Gene expression changes in primary human nasal epithelial cells exposed to formaldehyde in vitro. Toxicol Lett. 2010 Oct 5;198(2):289-95.
• [17] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.