Details of Drug Off-Target (DOT)

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

• DOT Name: Ras-related protein Rab-24 (RAB24)
• Gene Name: RAB24
• Related Disease:
  Hereditary ataxia
  Advanced cancer
  Hepatocellular carcinoma
• UniProt ID: RAB24_HUMAN
• Pfam ID: PF00071
• Sequence:
  MSGQRVDVKVVMLGKEYVGKTSLVERYVHDRFLVGPYQNTIGAAFVAKVMSVGDRTVTLG
  IWDTAGSERYEAMSRIYYRGAKAAIVCYDLTDSSSFERAKFWVKELRSLEEGCQIYLCGT
  KSDLLEEDRRRRRVDFHDVQDYADNIKAQLFETSSKTGQSVDELFQKVAEDYVSVAAFQV
  MTEDKGVDLGQKPNPYFYSCCHH
• Function: May be involved in autophagy-related processes.
• Reactome Pathway:
  RAB geranylgeranylation (R-HSA-8873719)
  Neutrophil degranulation (R-HSA-6798695)

Molecular Interaction Atlas (MIA) of This DOT

3 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Hereditary ataxia	DIS6JNI3	Strong	Genetic Variation	[1]
Advanced cancer	DISAT1Z9	moderate	Biomarker	[2]
Hepatocellular carcinoma	DIS0J828	moderate	Altered Expression	[2]

12 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-24 (RAB24).	[3]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Ras-related protein Rab-24 (RAB24).	[4]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Ras-related protein Rab-24 (RAB24).	[5]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Ras-related protein Rab-24 (RAB24).	[6]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Ras-related protein Rab-24 (RAB24).	[7]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide increases the expression of Ras-related protein Rab-24 (RAB24).	[8]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Ras-related protein Rab-24 (RAB24).	[9]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Ras-related protein Rab-24 (RAB24).	[11]
THAPSIGARGIN	DMDMQIE	Preclinical	THAPSIGARGIN increases the expression of Ras-related protein Rab-24 (RAB24).	[12]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Ras-related protein Rab-24 (RAB24).	[13]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Ras-related protein Rab-24 (RAB24).	[14]
Coumestrol	DM40TBU	Investigative	Coumestrol decreases the expression of Ras-related protein Rab-24 (RAB24).	[15]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of Ras-related protein Rab-24 (RAB24).	[10]

References

• [1] Canine hereditary ataxia in old english sheepdogs and gordon setters is associated with a defect in the autophagy gene encoding RAB24.PLoS Genet. 2014 Feb 6;10(2):e1003991. doi: 10.1371/journal.pgen.1003991. eCollection 2014 Feb.
• [2] KDM4B-mediated epigenetic silencing of miRNA-615-5p augments RAB24 to facilitate malignancy of hepatoma cells.Oncotarget. 2017 Mar 14;8(11):17712-17725. doi: 10.18632/oncotarget.10832.
• [3] 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.
• [4] 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.
• [5] Phenotypic characterization of retinoic acid differentiated SH-SY5Y cells by transcriptional profiling. PLoS One. 2013 May 28;8(5):e63862.
• [6] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [7] 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.
• [8] Essential role of cell cycle regulatory genes p21 and p27 expression in inhibition of breast cancer cells by arsenic trioxide. Med Oncol. 2011 Dec;28(4):1225-54.
• [9] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [10] 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.
• [11] Bromodomain-containing protein 4 (BRD4) regulates RNA polymerase II serine 2 phosphorylation in human CD4+ T cells. J Biol Chem. 2012 Dec 14;287(51):43137-55.
• [12] Endoplasmic reticulum stress impairs insulin signaling through mitochondrial damage in SH-SY5Y cells. Neurosignals. 2012;20(4):265-80.
• [13] Isobaric tags for relative and absolute quantitation-based proteomics analysis of the effect of ginger oil on bisphenol A-induced breast cancer cell proliferation. Oncol Lett. 2021 Feb;21(2):101. doi: 10.3892/ol.2020.12362. Epub 2020 Dec 8.
• [14] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.
• [15] Pleiotropic combinatorial transcriptomes of human breast cancer cells exposed to mixtures of dietary phytoestrogens. Food Chem Toxicol. 2009 Apr;47(4):787-95.