Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTBPUHV9)

• DOT Name: Ras-related protein Rab-8B (RAB8B)
• Gene Name: RAB8B
• UniProt ID: RAB8B_HUMAN
• Pfam ID: PF00071
• Sequence:
  MAKTYDYLFKLLLIGDSGVGKTCLLFRFSEDAFNTTFISTIGIDFKIRTIELDGKKIKLQ
  IWDTAGQERFRTITTAYYRGAMGIMLVYDITNEKSFDNIKNWIRNIEEHASSDVERMILG
  NKCDMNDKRQVSKERGEKLAIDYGIKFLETSAKSSANVEEAFFTLARDIMTKLNRKMNDS
  NSAGAGGPVKITENRSKKTSFFRCSLL
• 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 may be involved in polarized vesicular trafficking and neurotransmitter release. May participate in cell junction dynamics in Sertoli cells. May participate in the export of a subset of neosynthesized proteins through a Rab8-Rab10-Rab11-dependent endososomal export route.
• KEGG Pathway: Tight junction (hsa04530)
• Reactome Pathway:
  RAB geranylgeranylation (R-HSA-8873719)
  RAB GEFs exchange GTP for GDP on RABs (R-HSA-8876198)
  TBC/RABGAPs (R-HSA-8854214)

Molecular Interaction Atlas (MIA) of This DOT

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the expression of Ras-related protein Rab-8B (RAB8B).	[1]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Ras-related protein Rab-8B (RAB8B).	[2]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Ras-related protein Rab-8B (RAB8B).	[3]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Ras-related protein Rab-8B (RAB8B).	[4]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Ras-related protein Rab-8B (RAB8B).	[5]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Ras-related protein Rab-8B (RAB8B).	[6]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Ras-related protein Rab-8B (RAB8B).	[7]
Vorinostat	DMWMPD4	Approved	Vorinostat increases the expression of Ras-related protein Rab-8B (RAB8B).	[1]
Testosterone	DM7HUNW	Approved	Testosterone decreases the expression of Ras-related protein Rab-8B (RAB8B).	[8]
Phenobarbital	DMXZOCG	Approved	Phenobarbital affects the expression of Ras-related protein Rab-8B (RAB8B).	[9]
Demecolcine	DMCZQGK	Approved	Demecolcine increases the expression of Ras-related protein Rab-8B (RAB8B).	[10]
Bortezomib	DMNO38U	Approved	Bortezomib decreases the expression of Ras-related protein Rab-8B (RAB8B).	[11]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of Ras-related protein Rab-8B (RAB8B).	[12]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Ras-related protein Rab-8B (RAB8B).	[13]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A affects the expression of Ras-related protein Rab-8B (RAB8B).	[14]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of Ras-related protein Rab-8B (RAB8B).	[10]
Milchsaure	DM462BT	Investigative	Milchsaure affects the expression of Ras-related protein Rab-8B (RAB8B).	[15]
Sulforaphane	DMQY3L0	Investigative	Sulforaphane increases the expression of Ras-related protein Rab-8B (RAB8B).	[16]

References

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• [3] 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.
• [4] Bringing in vitro analysis closer to in vivo: studying doxorubicin toxicity and associated mechanisms in 3D human microtissues with PBPK-based dose modelling. Toxicol Lett. 2018 Sep 15;294:184-192.
• [5] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [6] Low doses of cisplatin induce gene alterations, cell cycle arrest, and apoptosis in human promyelocytic leukemia cells. Biomark Insights. 2016 Aug 24;11:113-21.
• [7] Comparison of phenotypic and transcriptomic effects of false-positive genotoxins, true genotoxins and non-genotoxins using HepG2 cells. Mutagenesis. 2011 Sep;26(5):593-604.
• [8] The exosome-like vesicles derived from androgen exposed-prostate stromal cells promote epithelial cells proliferation and epithelial-mesenchymal transition. Toxicol Appl Pharmacol. 2021 Jan 15;411:115384. doi: 10.1016/j.taap.2020.115384. Epub 2020 Dec 25.
• [9] 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.
• [10] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
• [11] The proapoptotic effect of zoledronic acid is independent of either the bone microenvironment or the intrinsic resistance to bortezomib of myeloma cells and is enhanced by the combination with arsenic trioxide. Exp Hematol. 2011 Jan;39(1):55-65.
• [12] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [13] Alternatives for the worse: Molecular insights into adverse effects of bisphenol a and substitutes during human adipocyte differentiation. Environ Int. 2021 Nov;156:106730. doi: 10.1016/j.envint.2021.106730. Epub 2021 Jun 27.
• [14] A trichostatin A expression signature identified by TempO-Seq targeted whole transcriptome profiling. PLoS One. 2017 May 25;12(5):e0178302. doi: 10.1371/journal.pone.0178302. eCollection 2017.
• [15] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.
• [16] Sulforaphane-induced apoptosis in human leukemia HL-60 cells through extrinsic and intrinsic signal pathways and altering associated genes expression assayed by cDNA microarray. Environ Toxicol. 2017 Jan;32(1):311-328.