Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT1GW0K2)

• DOT Name: TBC1 domain family member 3C (TBC1D3)
• Gene Name: TBC1D3
• Related Disease:
  Breast cancer
  Breast carcinoma
  Prostate cancer
  Prostate carcinoma
  Prostate neoplasm
• UniProt ID: TBC3C_HUMAN
• Pfam ID: PF00566
• Sequence:
  MDVVEVAGSWWAQEREDIIMKYEKGHRAGLPEDKGPKPFRSYNNNVDHLGIVHETELPPL
  TAREAKQIRREISRKSKWVDMLGDWEKYKSSRKLIDRAYKGMPMNIRGPMWSVLLNTEEM
  KLKNPGRYQIMKEKGKRSSEHIQRIDRDVSGTLRKHIFFRDRYGTKQRELLHILLAYEEY
  NPEVGYCRDLSHIAALFLLYLPEEDAFWALVQLLASERHSLQGFHSPNGGTVQGLQDQQE
  HVVATSQPKTMGHQDKKDLCGQCSPLGCLIRILIDGISLGLTLRLWDVYLVEGEQALMPI
  TRIAFKVQQKRLTKTSRCGPWARFCNRFVDTWARDEDTVLKHLRASMKKLTRKKGDLPPP
  AKPEQGSSASRPVPASRGGKTLCKGDRQAPPGPPARFPRPIWSASPPRAPRSSTPCPGGA
  VREDTYPVGTQGVPSPALAQGGPQGSWRFLQWNSMPRLPTDLDVEGPWFRHYDFRQSCWV
  RAISQEDQLAPCWQAEHPAERVRSAFAAPSTDSDQGTPFRARDEQQCAPTSGPCLCGLHL
  ESSQFPPGF
• Function: Acts as a GTPase activating protein for RAB5. Does not act on RAB4 or RAB11.
• Tissue Specificity: Expressed in pancreas, thymus and testis.

Molecular Interaction Atlas (MIA) of This DOT

5 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Breast cancer	DIS7DPX1	Strong	Biomarker	[1]
Breast carcinoma	DIS2UE88	Strong	Biomarker	[1]
Prostate cancer	DISF190Y	Strong	Altered Expression	[2]
Prostate carcinoma	DISMJPLE	Strong	Biomarker	[2]
Prostate neoplasm	DISHDKGQ	Strong	Genetic Variation	[3]

1 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 3C (TBC1D3).	[4]

3 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 3C (TBC1D3).	[5]
Amiodarone	DMUTEX3	Phase 2/3 Trial	Amiodarone increases the expression of TBC1 domain family member 3C (TBC1D3).	[6]
Tocopherol	DMBIJZ6	Phase 2	Tocopherol decreases the expression of TBC1 domain family member 3C (TBC1D3).	[7]

References

• [1] Up-regulation of OLR1 expression by TBC1D3 through activation of TNF/NF-B pathway promotes the migration of human breast cancer cells.Cancer Lett. 2017 Nov 1;408:60-70. doi: 10.1016/j.canlet.2017.08.021. Epub 2017 Aug 24.
• [2] PRC17, a novel oncogene encoding a Rab GTPase-activating protein, is amplified in prostate cancer.Cancer Res. 2002 Oct 1;62(19):5420-4.
• [3] TBC1D3, a hominoid oncoprotein, is encoded by a cluster of paralogues located on chromosome 17q12.Genomics. 2006 Dec;88(6):731-736. doi: 10.1016/j.ygeno.2006.05.009. Epub 2006 Jul 24.
• [4] 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.
• [5] Cyclosporine A--induced oxidative stress in human renal mesangial cells: a role for ERK 1/2 MAPK signaling. Toxicol Sci. 2012 Mar;126(1):101-13.
• [6] Identification by automated screening of a small molecule that selectively eliminates neural stem cells derived from hESCs but not dopamine neurons. PLoS One. 2009 Sep 23;4(9):e7155.
• [7] 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.