Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT75ZWLB)

• DOT Name: TBC1 domain family member 17 (TBC1D17)
• Gene Name: TBC1D17
• UniProt ID: TBC17_HUMAN
• Pfam ID: PF12068 ; PF00566
• Sequence:
  MEGAGYRVVFEKGGVYLHTSAKKYQDRDSLIAGVIRVVEKDNDVLLHWAPVEEAGDSTQI
  LFSKKDSSGGDSCASEEEPTFDPGYEPDWAVISTVRPQLCHSEPTRGAEPSCPQGSWAFS
  VSLGELKSIRRSKPGLSWAYLVLVTQAGGSLPALHFHRGGTRALLRVLSRYLLLASSPQD
  SRLYLVFPHDSSALSNSFHHLQLFDQDSSNVVSRFLQDPYSTTFSSFSRVTNFFRGALQP
  QPEGAASDLPPPPDDEPEPGFEVISCVELGPRPTVERGPPVTEEEWARHVGPEGRLQQVP
  ELKNRIFSGGLSPSLRREAWKFLLGYLSWEGTAEEHKAHIRKKTDEYFRMKLQWKSVSPE
  QERRNSLLHGYRSLIERDVSRTDRTNKFYEGPENPGLGLLNDILLTYCMYHFDLGYVQGM
  SDLLSPILYVIQNEVDAFWCFCGFMELVQGNFEESQETMKRQLGRLLLLLRVLDPLLCDF
  LDSQDSGSLCFCFRWLLIWFKREFPFPDVLRLWEVLWTGLPGPNLHLLVACAILDMERDT
  LMLSGFGSNEILKHINELTMKLSVEDVLTRAEALHRQLTACPELPHNVQEILGLAPPAEP
  HSPSPTASPLPLSPTRAPPTPPPSTDTAPQPDSSLEILPEEEDEGADS
• Function: Probable RAB GTPase-activating protein that inhibits RAB8A/B function. Reduces Rab8 recruitment to tubules emanating from the endocytic recycling compartment (ERC) and inhibits Rab8-mediated endocytic trafficking, such as that of transferrin receptor (TfR). Involved in regulation of autophagy.
• KEGG Pathway: Mitophagy - animal (hsa04137)
• Reactome Pathway: TBC/RABGAPs (R-HSA-8854214)

Molecular Interaction Atlas (MIA) of This DOT

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 TBC1 domain family member 17 (TBC1D17).	[1]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene affects the methylation of TBC1 domain family member 17 (TBC1D17).	[9]
Coumarin	DM0N8ZM	Investigative	Coumarin increases the phosphorylation of TBC1 domain family member 17 (TBC1D17).	[10]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of TBC1 domain family member 17 (TBC1D17).	[2]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of TBC1 domain family member 17 (TBC1D17).	[3]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of TBC1 domain family member 17 (TBC1D17).	[4]
Decitabine	DMQL8XJ	Approved	Decitabine decreases the expression of TBC1 domain family member 17 (TBC1D17).	[5]
Marinol	DM70IK5	Approved	Marinol increases the expression of TBC1 domain family member 17 (TBC1D17).	[6]
Niclosamide	DMJAGXQ	Approved	Niclosamide increases the expression of TBC1 domain family member 17 (TBC1D17).	[7]
Exemestane	DM9HPW3	Approved	Exemestane increases the expression of TBC1 domain family member 17 (TBC1D17).	[8]

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] 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.
• [3] 17-Estradiol Activates HSF1 via MAPK Signaling in ER-Positive Breast Cancer Cells. Cancers (Basel). 2019 Oct 11;11(10):1533. doi: 10.3390/cancers11101533.
• [4] 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.
• [5] DNA methylation inhibits p53-mediated survivin repression. Oncogene. 2009 May 14;28(19):2046-50. doi: 10.1038/onc.2009.62. Epub 2009 Apr 13.
• [6] THC exposure of human iPSC neurons impacts genes associated with neuropsychiatric disorders. Transl Psychiatry. 2018 Apr 25;8(1):89. doi: 10.1038/s41398-018-0137-3.
• [7] Mitochondrial Uncoupling Induces Epigenome Remodeling and Promotes Differentiation in Neuroblastoma. Cancer Res. 2023 Jan 18;83(2):181-194. doi: 10.1158/0008-5472.CAN-22-1029.
• [8] Effects of aromatase inhibitors on human osteoblast and osteoblast-like cells: a possible androgenic bone protective effects induced by exemestane. Bone. 2007 Apr;40(4):876-87. doi: 10.1016/j.bone.2006.11.029. Epub 2006 Dec 28.
• [9] Effect of aflatoxin B(1), benzo[a]pyrene, and methapyrilene on transcriptomic and epigenetic alterations in human liver HepaRG cells. Food Chem Toxicol. 2018 Nov;121:214-223. doi: 10.1016/j.fct.2018.08.034. Epub 2018 Aug 26.
• [10] 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.