Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTR2CI46)

• DOT Name: TBC1 domain family member 10A (TBC1D10A)
• Synonyms: EBP50-PDX interactor of 64 kDa; EPI64 protein; Rab27A-GAP-alpha
• Gene Name: TBC1D10A
• Related Disease:
  Breast cancer
  Breast carcinoma
• UniProt ID: TB10A_HUMAN
• Pfam ID: PF00566
• Sequence:
  MAKSNGENGPRAPAAGESLSGTRESLAQGPDAATTDELSSLGSDSEANGFAERRIDKFGF
  IVGSQGAEGALEEVPLEVLRQRESKWLDMLNNWDKWMAKKHKKIRLRCQKGIPPSLRGRA
  WQYLSGGKVKLQQNPGKFDELDMSPGDPKWLDVIERDLHRQFPFHEMFVSRGGHGQQDLF
  RVLKAYTLYRPEEGYCQAQAPIAAVLLMHMPAEQAFWCLVQICEKYLPGYYSEKLEAIQL
  DGEILFSLLQKVSPVAHKHLSRQKIDPLLYMTEWFMCAFSRTLPWSSVLRVWDMFFCEGV
  KIIFRVGLVLLKHALGSPEKVKACQGQYETIERLRSLSPKIMQEAFLVQEVVELPVTERQ
  IEREHLIQLRRWQETRGELQCRSPPRLHGAKAILDAEPGPRPALQPSPSIRLPLDAPLPG
  SKAKPKPPKQAQKEQRKQMKGRGQLEKPPAPNQAMVVAAAGDACPPQHVPPKDSAPKDSA
  PQDLAPQVSAHHRSQESLTSQESEDTYL
• Function: Acts as a GTPase-activating protein for RAB27A, but not for RAB2A, RAB3A, nor RAB4A.
• Reactome Pathway: TBC/RABGAPs (R-HSA-8854214)

Molecular Interaction Atlas (MIA) of This DOT

2 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Breast cancer	DIS7DPX1	Strong	Genetic Variation	[1]
Breast carcinoma	DIS2UE88	Strong	Genetic Variation	[1]

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 10A (TBC1D10A).	[2]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of TBC1 domain family member 10A (TBC1D10A).	[8]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of TBC1 domain family member 10A (TBC1D10A).	[9]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of TBC1 domain family member 10A (TBC1D10A).	[3]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of TBC1 domain family member 10A (TBC1D10A).	[4]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of TBC1 domain family member 10A (TBC1D10A).	[5]
Niclosamide	DMJAGXQ	Approved	Niclosamide increases the expression of TBC1 domain family member 10A (TBC1D10A).	[6]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of TBC1 domain family member 10A (TBC1D10A).	[7]

References

• [1] RNA variant identification discrepancy among splice-aware alignment algorithms.PLoS One. 2018 Aug 2;13(8):e0201822. doi: 10.1371/journal.pone.0201822. eCollection 2018.
• [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] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [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] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [6] 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.
• [7] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [8] 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.
• [9] 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.