Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTIQ484I)

• DOT Name: Ras-related protein Rab-13 (RAB13)
• Synonyms: Cell growth-inhibiting gene 4 protein
• Gene Name: RAB13
• Related Disease:
  Bone osteosarcoma
  Gastric cancer
  Osteosarcoma
  Stomach cancer
  Advanced cancer
• UniProt ID: RAB13_HUMAN
• Pfam ID: PF00071
• Sequence:
  MAKAYDHLFKLLLIGDSGVGKTCLIIRFAEDNFNNTYISTIGIDFKIRTVDIEGKKIKLQ
  VWDTAGQERFKTITTAYYRGAMGIILVYDITDEKSFENIQNWMKSIKENASAGVERLLLG
  NKCDMEAKRKVQKEQADKLAREHGIRFFETSAKSSMNVDEAFSSLARDILLKSGGRRSGN
  GNKPPSTDLKTCDKKNTNKCSLG
• 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 sets of downstream effectors directly responsible for vesicle formation, movement, tethering and fusion. That Rab is involved in endocytic recycling and regulates the transport to the plasma membrane of transmembrane proteins like the tight junction protein OCLN/occludin. Thereby, it regulates the assembly and the activity of tight junctions. Moreover, it may also regulate tight junction assembly by activating the PKA signaling pathway and by reorganizing the actin cytoskeleton through the activation of the downstream effectors PRKACA and MICALL2 respectively. Through its role in tight junction assembly, may play a role in the establishment of Sertoli cell barrier. Plays also a role in angiogenesis through regulation of endothelial cells chemotaxis. Also involved in neurite outgrowth. Has also been proposed to play a role in post-Golgi membrane trafficking from the TGN to the recycling endosome. Finally, it has been involved in insulin-induced transport to the plasma membrane of the glucose transporter GLUT4 and therefore may play a role in glucose homeostasis.
• Tissue Specificity: Detected in several types of epithelia, including intestine, kidney, liver and in endothelial cells.
• KEGG Pathway: Tight junction (hsa04530)
• Reactome Pathway:
  RAB geranylgeranylation (R-HSA-8873719)
  RAB GEFs exchange GTP for GDP on RABs (R-HSA-8876198)
  Translocation of SLC2A4 (GLUT4) to the plasma membrane (R-HSA-1445148)

Molecular Interaction Atlas (MIA) of This DOT

5 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Bone osteosarcoma	DIST1004	Definitive	Biomarker	[1]
Gastric cancer	DISXGOUK	Definitive	Altered Expression	[2]
Osteosarcoma	DISLQ7E2	Definitive	Biomarker	[1]
Stomach cancer	DISKIJSX	Definitive	Altered Expression	[2]
Advanced cancer	DISAT1Z9	Strong	Altered Expression	[3]

This DOT Affected the Drug Response of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Topotecan	DMP6G8T	Approved	Ras-related protein Rab-13 (RAB13) affects the response to substance of Topotecan.	[13]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Ras-related protein Rab-13 (RAB13).	[4]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Ras-related protein Rab-13 (RAB13).	[5]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide increases the expression of Ras-related protein Rab-13 (RAB13).	[6]
Decitabine	DMQL8XJ	Approved	Decitabine increases the expression of Ras-related protein Rab-13 (RAB13).	[7]
Phenobarbital	DMXZOCG	Approved	Phenobarbital affects the expression of Ras-related protein Rab-13 (RAB13).	[8]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Ras-related protein Rab-13 (RAB13).	[9]
SB-431542	DM0YOXQ	Preclinical	SB-431542 increases the expression of Ras-related protein Rab-13 (RAB13).	[10]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Ras-related protein Rab-13 (RAB13).	[12]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Azacitidine	DMTA5OE	Approved	Azacitidine decreases the methylation of Ras-related protein Rab-13 (RAB13).	[7]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the methylation of Ras-related protein Rab-13 (RAB13).	[11]

References

• [1] A Novel lncRNA MYOSLID/miR-1286/RAB13 Axis Plays a Critical Role in Osteosarcoma Progression.Cancer Manag Res. 2019 Dec 10;11:10345-10351. doi: 10.2147/CMAR.S231376. eCollection 2019.
• [2] RAB13 as a novel prognosis marker promotes proliferation and chemotherapeutic resistance in gastric cancer.Biochem Biophys Res Commun. 2019 Oct 29;519(1):113-120. doi: 10.1016/j.bbrc.2019.08.141. Epub 2019 Aug 29.
• [3] Garlic extract in bladder cancer prevention: Evidence from T24 bladder cancer cell xenograft model, tissue microarray, and gene network analysis.Int J Oncol. 2017 Jul;51(1):204-212. doi: 10.3892/ijo.2017.3993. Epub 2017 May 11.
• [4] Transcriptional and Metabolic Dissection of ATRA-Induced Granulocytic Differentiation in NB4 Acute Promyelocytic Leukemia Cells. Cells. 2020 Nov 5;9(11):2423. doi: 10.3390/cells9112423.
• [5] 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.
• [6] 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.
• [7] The DNA methyltransferase inhibitors azacitidine, decitabine and zebularine exert differential effects on cancer gene expression in acute myeloid leukemia cells. Leukemia. 2009 Jun;23(6):1019-28.
• [8] Reproducible chemical-induced changes in gene expression profiles in human hepatoma HepaRG cells under various experimental conditions. Toxicol In Vitro. 2009 Apr;23(3):466-75. doi: 10.1016/j.tiv.2008.12.018. Epub 2008 Dec 30.
• [9] Cell-based two-dimensional morphological assessment system to predict cancer drug-induced cardiotoxicity using human induced pluripotent stem cell-derived cardiomyocytes. Toxicol Appl Pharmacol. 2019 Nov 15;383:114761. doi: 10.1016/j.taap.2019.114761. Epub 2019 Sep 15.
• [10] Activin/nodal signaling switches the terminal fate of human embryonic stem cell-derived trophoblasts. J Biol Chem. 2015 Apr 3;290(14):8834-48.
• [11] Expression and DNA methylation changes in human breast epithelial cells after bisphenol A exposure. Int J Oncol. 2012 Jul;41(1):369-77.
• [12] 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.
• [13] 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.