Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT4RG5U7)

• DOT Name: Protein FAM76B (FAM76B)
• Gene Name: FAM76B
• Related Disease: Pulmonary tuberculosis
• UniProt ID: FA76B_HUMAN
• Pfam ID: PF16046
• Sequence:
  MAASALYACTKCTQRYPFEELSQGQQLCKECRIAHPIVKCTYCRSEFQQESKTNTICKKC
  AQNVKQFGTPKPCQYCNIIAAFIGTKCQRCTNSEKKYGPPQTCEQCKQQCAFDRKEEGRR
  KVDGKLLCWLCTLSYKRVLQKTKEQRKSLGSSHSNSSSSSLTEKDQHHPKHHHHHHHHHH
  RHSSSHHKISNLSPEEEQGLWKQSHKSSATIQNETPKKKPKLESKPSNGDSSSINQSADS
  GGTDNFVLISQLKEEVMSLKRLLQQRDQTILEKDKKLTELKADFQYQESNLRTKMNSMEK
  AHKETVEQLQAKNRELLKQVAALSKGKKFDKSGSILTSP

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Pulmonary tuberculosis	DIS6FLUM	moderate	Genetic Variation	[1]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the methylation of Protein FAM76B (FAM76B).	[2]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 decreases the phosphorylation of Protein FAM76B (FAM76B).	[13]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Protein FAM76B (FAM76B).	[3]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Protein FAM76B (FAM76B).	[4]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide decreases the expression of Protein FAM76B (FAM76B).	[5]
Vorinostat	DMWMPD4	Approved	Vorinostat increases the expression of Protein FAM76B (FAM76B).	[6]
Testosterone	DM7HUNW	Approved	Testosterone decreases the expression of Protein FAM76B (FAM76B).	[7]
Fluorouracil	DMUM7HZ	Approved	Fluorouracil decreases the expression of Protein FAM76B (FAM76B).	[8]
Demecolcine	DMCZQGK	Approved	Demecolcine decreases the expression of Protein FAM76B (FAM76B).	[9]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of Protein FAM76B (FAM76B).	[10]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide decreases the expression of Protein FAM76B (FAM76B).	[12]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Protein FAM76B (FAM76B).	[14]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of Protein FAM76B (FAM76B).	[15]

1 Drug(s) Affected the Protein Interaction/Cellular Processes of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
DNCB	DMDTVYC	Phase 2	DNCB affects the binding of Protein FAM76B (FAM76B).	[11]

References

• [1] Comprehensive analysis of long non-coding RNAs expression pattern in the pathogenesis of pulmonary tuberculosis.Genomics. 2020 Mar;112(2):1970-1977. doi: 10.1016/j.ygeno.2019.11.009. Epub 2019 Nov 20.
• [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] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [4] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [5] Oxidative stress modulates theophylline effects on steroid responsiveness. Biochem Biophys Res Commun. 2008 Dec 19;377(3):797-802.
• [6] Definition of transcriptome-based indices for quantitative characterization of chemically disturbed stem cell development: introduction of the STOP-Toxukn and STOP-Toxukk tests. Arch Toxicol. 2017 Feb;91(2):839-864.
• [7] 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.
• [8] Pharmacogenomic identification of novel determinants of response to chemotherapy in colon cancer. Cancer Res. 2006 Mar 1;66(5):2765-77.
• [9] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
• [10] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [11] Proteomic analysis of the cellular response to a potent sensitiser unveils the dynamics of haptenation in living cells. Toxicology. 2020 Dec 1;445:152603. doi: 10.1016/j.tox.2020.152603. Epub 2020 Sep 28.
• [12] Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
• [13] 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.
• [14] Bisphenol A induces DSB-ATM-p53 signaling leading to cell cycle arrest, senescence, autophagy, stress response, and estrogen release in human fetal lung fibroblasts. Arch Toxicol. 2018 Apr;92(4):1453-1469.
• [15] 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.