Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTV5UGNC)

• DOT Name: TBC1 domain family member 9B (TBC1D9B)
• Gene Name: TBC1D9B
• UniProt ID: TBC9B_HUMAN
• Pfam ID: PF02893 ; PF00566
• Sequence:
  MWLSPEEVLVANALWVTERANPFFVLQRRRGHGRGGGLTGLLVGTLDVVLDSSARVAPYR
  ILHQTQDSQVYWTVACGSSRKEITKHWEWLENNLLQTLSIFDSEEDITTFVKGKIHGIIA
  EENKNLQPQGDEDPGKFKEAELKMRKQFGMPEGEKLVNYYSCSYWKGRVPRQGWLYLTVN
  HLCFYSFLLGKEVSLVVQWVDITRLEKNATLLFPESIRVDTRDQELFFSMFLNIGETFKL
  MEQLANLAMRQLLDSEGFLEDKALPRPIRPHRNISALKRDLDARAKNECYRATFRLPRDE
  RLDGHTSCTLWTPFNKLHIPGQMFISNNYICFASKEEDACHLIIPLREVTIVEKADSSSV
  LPSPLSISTKSKMTFLFANLKDRDFLVQRISDFLQKTPSKQPGSIGSRKASVVDPSTESS
  PAPQEGSEQPASPASPLSSRQSFCAQEAPTASQGLLKLFQKNSPMEDLGAKGAKEKMKEE
  SWHIHFFEYGRGVCMYRTAKTRALVLKGIPESLRGELWLLFSGAWNEMVTHPGYYAELVE
  KSTGKYSLATEEIERDLHRSMPEHPAFQNELGIAALRRVLTAYAFRNPTIGYCQAMNIVT
  SVLLLYGSEEEAFWLLVALCERMLPDYYNTRVVGALVDQGIFEELTRDFLPQLSEKMQDL
  GVISSISLSWFLTLFLSVMPFESAVVIVDCFFYEGIKVILQVALAVLDANMEQLLGCSDE
  GEAMTMLGRYLDNVVNKQSVSPPIPHLRALLSSSDDPPAEVDIFELLKVSYEKFSSLRAE
  DIEQMRFKQRLKVIQSLEDTAKRSVVRAIPVDIGFSIEELEDLYMVFKAKHLASQYWGCS
  RTMAGRRDPSLPYLEQYRIDASQFRELFASLTPWACGSHTPLLAGRMFRLLDENKDSLIN
  FKEFVTGMSGMYHGDLTEKLKVLYKLHLPPALSPEEAESALEAAHYFTEDSSSEASPLAS
  DLDLFLPWEAQEALPQEEQEGSGSEERGEEKGTSSPDYRHYLRMWAKEKEAQKETIKDLP
  KMNQEQFIELCKTLYNMFSEDPMEQDLYHAIATVASLLLRIGEVGKKFSARTGRKPRDCA
  TEEDEPPAPELHQDAARELQPPAAGDPQAKAGGDTHLGKAPQESQVVVEGGSGEGQGSPS
  QLLSDDETKDDMSMSSYSVVSTGSLQCEDLADDTVLVGGEACSPTARIGGTVDTDWCISF
  EQILASILTESVLVNFFEKRVDIGLKIKDQKKVERQFSTASDHEQPGVSG
• Function: May act as a GTPase-activating protein for Rab family protein(s).

Molecular Interaction Atlas (MIA) of This DOT

4 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 TBC1 domain family member 9B (TBC1D9B).	[1]
Quercetin	DM3NC4M	Approved	Quercetin increases the phosphorylation of TBC1 domain family member 9B (TBC1D9B).	[4]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 increases the phosphorylation of TBC1 domain family member 9B (TBC1D9B).	[4]
Coumarin	DM0N8ZM	Investigative	Coumarin increases the phosphorylation of TBC1 domain family member 9B (TBC1D9B).	[4]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of TBC1 domain family member 9B (TBC1D9B).	[2]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of TBC1 domain family member 9B (TBC1D9B).	[3]
Selenium	DM25CGV	Approved	Selenium increases the expression of TBC1 domain family member 9B (TBC1D9B).	[5]
Menadione	DMSJDTY	Approved	Menadione affects the expression of TBC1 domain family member 9B (TBC1D9B).	[6]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of TBC1 domain family member 9B (TBC1D9B).	[7]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of TBC1 domain family member 9B (TBC1D9B).	[8]
Deguelin	DMXT7WG	Investigative	Deguelin decreases the expression of TBC1 domain family member 9B (TBC1D9B).	[9]

References

• [1] 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.
• [2] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [3] 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.
• [4] 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.
• [5] Selenium and vitamin E: cell type- and intervention-specific tissue effects in prostate cancer. J Natl Cancer Inst. 2009 Mar 4;101(5):306-20.
• [6] Global gene expression analysis reveals differences in cellular responses to hydroxyl- and superoxide anion radical-induced oxidative stress in caco-2 cells. Toxicol Sci. 2010 Apr;114(2):193-203. doi: 10.1093/toxsci/kfp309. Epub 2009 Dec 31.
• [7] New insights into BaP-induced toxicity: role of major metabolites in transcriptomics and contribution to hepatocarcinogenesis. Arch Toxicol. 2016 Jun;90(6):1449-58.
• [8] Identification of mechanisms of action of bisphenol a-induced human preadipocyte differentiation by transcriptional profiling. Obesity (Silver Spring). 2014 Nov;22(11):2333-43.
• [9] Neurotoxicity and underlying cellular changes of 21 mitochondrial respiratory chain inhibitors. Arch Toxicol. 2021 Feb;95(2):591-615. doi: 10.1007/s00204-020-02970-5. Epub 2021 Jan 29.