Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTT614GF)

• DOT Name: TBC1 domain family member 14 (TBC1D14)
• Gene Name: TBC1D14
• UniProt ID: TBC14_HUMAN
• PDB ID: 2QQ8
• Pfam ID: PF00566
• Sequence:
  MTDGKLSTSTNGVAFMGILDGRPGNPLQNLQHVNLKAPRLLSAPEYGPKLKLRALEDRHS
  LQSVDSGIPTLEIGNPEPVPCSAVHVRRKQSDSDLIPERAFQSACALPSCAPPAPSSTER
  EQSVRKSSTFPRTGYDSVKLYSPTSKALTRSDDVSVCSVSSLGTELSTTLSVSNEDILDL
  VVTSSSSAIVTLENDDDPQFTNVTLSSIKETRGLHQQDCVHEAEEGSKLKILGPFSNFFA
  RNLLARKQSARLDKHNDLGWKLFGKAPLRENAQKDSKRIQKEYEDKAGRPSKPPSPKQNV
  RKNLDFEPLSTTALILEDRPANLPAKPAEEAQKHRQQYEEMVVQAKKRELKEAQRRKKQL
  EERCRVEESIGNAVLTWNNEILPNWETMWCSRKVRDLWWQGIPPSVRGKVWSLAIGNELN
  ITHELFDICLARAKERWRSLSTGGSEVENEDAGFSAADREASLELIKLDISRTFPNLCIF
  QQGGPYHDMLHSILGAYTCYRPDVGYVQGMSFIAAVLILNLDTADAFIAFSNLLNKPCQM
  AFFRVDHGLMLTYFAAFEVFFEENLPKLFAHFKKNNLTPDIYLIDWIFTLYSKSLPLDLA
  CRIWDVFCRDGEEFLFRTALGILKLFEDILTKMDFIHMAQFLTRLPEDLPAEELFASIAT
  IQMQSRNKKWAQVLTALQKDSREMEKGSPSLRH
• Function: Plays a role in the regulation of starvation-induced autophagosome formation. Together with the TRAPPIII complex, regulates a constitutive trafficking step from peripheral recycling endosomes to the early Golgi, maintaining the cycling pool of ATG9 required for initiation of autophagy.
• Reactome Pathway: TBC/RABGAPs (R-HSA-8854214)

Molecular Interaction Atlas (MIA) of This DOT

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 TBC1 domain family member 14 (TBC1D14).	[1]
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of TBC1 domain family member 14 (TBC1D14).	[7]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of TBC1 domain family member 14 (TBC1D14).	[2]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of TBC1 domain family member 14 (TBC1D14).	[3]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of TBC1 domain family member 14 (TBC1D14).	[4]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of TBC1 domain family member 14 (TBC1D14).	[5]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of TBC1 domain family member 14 (TBC1D14).	[6]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of TBC1 domain family member 14 (TBC1D14).	[8]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of TBC1 domain family member 14 (TBC1D14).	[9]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of TBC1 domain family member 14 (TBC1D14).	[10]

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] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [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] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [5] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [6] 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.
• [7] Prenatal arsenic exposure and the epigenome: identifying sites of 5-methylcytosine alterations that predict functional changes in gene expression in newborn cord blood and subsequent birth outcomes. Toxicol Sci. 2015 Jan;143(1):97-106. doi: 10.1093/toxsci/kfu210. Epub 2014 Oct 10.
• [8] Transcriptional signature of human macrophages exposed to the environmental contaminant benzo(a)pyrene. Toxicol Sci. 2010 Apr;114(2):247-59.
• [9] 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.
• [10] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.