Details of Drug Off-Target (DOT)

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

• DOT Name: Ras-related protein Rab-3C (RAB3C)
• Gene Name: RAB3C
• UniProt ID: RAB3C_HUMAN
• PDB ID: 6Y7G
• Pfam ID: PF00071
• Sequence:
  MRHEAPMQMASAQDARYGQKDSSDQNFDYMFKLLIIGNSSVGKTSFLFRYADDSFTSAFV
  STVGIDFKVKTVFKNEKRIKLQIWDTAGQERYRTITTAYYRGAMGFILMYDITNEESFNA
  VQDWSTQIKTYSWDNAQVILVGNKCDMEDERVISTERGQHLGEQLGFEFFETSAKDNINV
  KQTFERLVDIICDKMSESLETDPAITAAKQNTRLKETPPPPQPNCAC
• Function: Protein transport. Probably involved in vesicular traffic.
• Tissue Specificity: Expressed in brain, placenta and lung.
• Reactome Pathway: RAB geranylgeranylation (R-HSA-8873719)

Molecular Interaction Atlas (MIA) of This DOT

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the expression of Ras-related protein Rab-3C (RAB3C).	[1]
Ciclosporin	DMAZJFX	Approved	Ciclosporin affects the expression of Ras-related protein Rab-3C (RAB3C).	[2]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Ras-related protein Rab-3C (RAB3C).	[3]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Ras-related protein Rab-3C (RAB3C).	[2]
Vorinostat	DMWMPD4	Approved	Vorinostat increases the expression of Ras-related protein Rab-3C (RAB3C).	[5]
Phenobarbital	DMXZOCG	Approved	Phenobarbital affects the expression of Ras-related protein Rab-3C (RAB3C).	[6]
Panobinostat	DM58WKG	Approved	Panobinostat increases the expression of Ras-related protein Rab-3C (RAB3C).	[5]
Malathion	DMXZ84M	Approved	Malathion decreases the expression of Ras-related protein Rab-3C (RAB3C).	[7]
Belinostat	DM6OC53	Phase 2	Belinostat increases the expression of Ras-related protein Rab-3C (RAB3C).	[5]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Ras-related protein Rab-3C (RAB3C).	[10]

3 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of Ras-related protein Rab-3C (RAB3C).	[4]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Ras-related protein Rab-3C (RAB3C).	[8]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the methylation of Ras-related protein Rab-3C (RAB3C).	[9]

References

• [1] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [2] Comparison of HepG2 and HepaRG by whole-genome gene expression analysis for the purpose of chemical hazard identification. Toxicol Sci. 2010 May;115(1):66-79.
• [3] Blood transcript immune signatures distinguish a subset of people with elevated serum ALT from others given acetaminophen. Clin Pharmacol Ther. 2016 Apr;99(4):432-41.
• [4] 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.
• [5] A transcriptome-based classifier to identify developmental toxicants by stem cell testing: design, validation and optimization for histone deacetylase inhibitors. Arch Toxicol. 2015 Sep;89(9):1599-618.
• [6] Dose- and time-dependent effects of phenobarbital on gene expression profiling in human hepatoma HepaRG cells. Toxicol Appl Pharmacol. 2009 Feb 1;234(3):345-60.
• [7] Exposure to Insecticides Modifies Gene Expression and DNA Methylation in Hematopoietic Tissues In Vitro. Int J Mol Sci. 2023 Mar 26;24(7):6259. doi: 10.3390/ijms24076259.
• [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.
• [10] From transient transcriptome responses to disturbed neurodevelopment: role of histone acetylation and methylation as epigenetic switch between reversible and irreversible drug effects. Arch Toxicol. 2014 Jul;88(7):1451-68.