Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT7NBUGQ)

• DOT Name: Ras-related protein Rab-17 (RAB17)
• Gene Name: RAB17
• Related Disease:
  Hepatocellular carcinoma
  Metastatic malignant neoplasm
  Non-small-cell lung cancer
  Advanced cancer
  Neoplasm
• UniProt ID: RAB17_HUMAN
• Pfam ID: PF00071
• Sequence:
  MAQAHRTPQPRAAPSQPRVFKLVLLGSGSVGKSSLALRYVKNDFKSILPTVGCAFFTKVV
  DVGATSLKLEIWDTAGQEKYHSVCHLYFRGANAALLVYDITRKDSFLKAQQWLKDLEEEL
  HPGEVLVMLVGNKTDLSQEREVTFQEGKEFADSQKLLFMETSAKLNHQVSEVFNTVAQEL
  LQRSDEEGQALRGDAAVALNKGPARQAKCCAH
• Function: The small GTPases Rab are key regulators of intracellular membrane trafficking, from the formation of transport vesicles to their fusion with membranes. Rabs cycle between an inactive GDP-bound form and an active GTP-bound form that is able to recruit to membranes different set of downstream effectors directly responsible for vesicle formation, movement, tethering and fusion. That Rab is involved in transcytosis, the directed movement of endocytosed material through the cell and its exocytosis from the plasma membrane at the opposite side. Mainly observed in epithelial cells, transcytosis mediates for instance, the transcellular transport of immunoglobulins from the basolateral surface to the apical surface. Most probably controls membrane trafficking through apical recycling endosomes in a post-endocytic step of transcytosis. Required for melanosome transport and release from melanocytes, it also regulates dendrite and dendritic spine development. May also play a role in cell migration.
• Tissue Specificity: Expressed in melanocytes (at protein level).
• KEGG Pathway: Efferocytosis (hsa04148)
• Reactome Pathway: RAB geranylgeranylation (R-HSA-8873719)

Molecular Interaction Atlas (MIA) of This DOT

5 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Hepatocellular carcinoma	DIS0J828	Strong	Biomarker	[1]
Metastatic malignant neoplasm	DIS86UK6	Strong	Biomarker	[1]
Non-small-cell lung cancer	DIS5Y6R9	Strong	Biomarker	[2]
Advanced cancer	DISAT1Z9	moderate	Biomarker	[3]
Neoplasm	DISZKGEW	moderate	Biomarker	[2]

This DOT Affected the Drug Response of 2 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Etoposide	DMNH3PG	Approved	Ras-related protein Rab-17 (RAB17) affects the response to substance of Etoposide.	[14]
Mitomycin	DMH0ZJE	Approved	Ras-related protein Rab-17 (RAB17) affects the response to substance of Mitomycin.	[14]

2 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 Ras-related protein Rab-17 (RAB17).	[4]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of Ras-related protein Rab-17 (RAB17).	[12]

9 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 Ras-related protein Rab-17 (RAB17).	[5]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Ras-related protein Rab-17 (RAB17).	[6]
Doxorubicin	DMVP5YE	Approved	Doxorubicin increases the expression of Ras-related protein Rab-17 (RAB17).	[7]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Ras-related protein Rab-17 (RAB17).	[8]
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of Ras-related protein Rab-17 (RAB17).	[9]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Ras-related protein Rab-17 (RAB17).	[10]
Panobinostat	DM58WKG	Approved	Panobinostat increases the expression of Ras-related protein Rab-17 (RAB17).	[11]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Ras-related protein Rab-17 (RAB17).	[11]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A affects the expression of Ras-related protein Rab-17 (RAB17).	[13]

References

• [1] Rab17 inhibits the tumourigenic properties of hepatocellular carcinomas via the Erk pathway.Tumour Biol. 2015 Aug;36(8):5815-24. doi: 10.1007/s13277-015-3251-3. Epub 2015 Feb 24.
• [2] Downregulation of Rab17 promotes cell proliferation and invasion in non-small cell lung cancer through STAT3/HIF-1/VEGF signaling.Thorac Cancer. 2020 Feb;11(2):379-388. doi: 10.1111/1759-7714.13278. Epub 2019 Dec 16.
• [3] Down-regulation of Rab17 promotes tumourigenic properties of hepatocellular carcinoma cells via Erk pathway.Int J Clin Exp Pathol. 2015 May 1;8(5):4963-71. eCollection 2015.
• [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] 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.
• [6] Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
• [7] RNA sequence analysis of inducible pluripotent stem cell-derived cardiomyocytes reveals altered expression of DNA damage and cell cycle genes in response to doxorubicin. Toxicol Appl Pharmacol. 2018 Oct 1;356:44-53.
• [8] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [9] Identification of vitamin D3 target genes in human breast cancer tissue. J Steroid Biochem Mol Biol. 2016 Nov;164:90-97.
• [10] Gene Expression Regulation and Pathway Analysis After Valproic Acid and Carbamazepine Exposure in a Human Embryonic Stem Cell-Based Neurodevelopmental Toxicity Assay. Toxicol Sci. 2015 Aug;146(2):311-20. doi: 10.1093/toxsci/kfv094. Epub 2015 May 15.
• [11] 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.
• [12] 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.
• [13] Comprehensive analysis of transcriptomic changes induced by low and high doses of bisphenol A in HepG2 spheroids in vitro and rat liver in vivo. Environ Res. 2019 Jun;173:124-134. doi: 10.1016/j.envres.2019.03.035. Epub 2019 Mar 18.
• [14] Gene expression profiling of 30 cancer cell lines predicts resistance towards 11 anticancer drugs at clinically achieved concentrations. Int J Cancer. 2006 Apr 1;118(7):1699-712. doi: 10.1002/ijc.21570.