Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTY10XRU)

• DOT Name: Ras-related GTP-binding protein B (RRAGB)
• Synonyms: Rag B; RagB; EC 3.6.5.-
• Gene Name: RRAGB
• UniProt ID: RRAGB_HUMAN
• EC Number: 3.6.5.-
• Pfam ID: PF04670
• Sequence:
  MEESDSEKTTEKENLGPRMDPPLGEPEGSLGWVLPNTAMKKKVLLMGKSGSGKTSMRSII
  FANYIARDTRRLGATILDRIHSLQINSSLSTYSLVDSVGNTKTFDVEHSHVRFLGNLVLN
  LWDCGGQDTFMENYFTSQRDNIFRNVEVLIYVFDVESRELEKDMHYYQSCLEAILQNSPD
  AKIFCLVHKMDLVQEDQRDLIFKEREEDLRRLSRPLECSCFRTSIWDETLYKAWSSIVYQ
  LIPNVQQLEMNLRNFAEIIEADEVLLFERATFLVISHYQCKEQRDAHRFEKISNIIKQFK
  LSCSKLAASFQSMEVRNSNFAAFIDIFTSNTYVMVVMSDPSIPSAATLINIRNARKHFEK
  LERVDGPKQCLLMR
• Function: Guanine nucleotide-binding protein that plays a crucial role in the cellular response to amino acid availability through regulation of the mTORC1 signaling cascade. Forms heterodimeric Rag complexes with RagC/RRAGC or RagD/RRAGD and cycles between an inactive GDP-bound and an active GTP-bound form: RagB/RRAGB is in its active form when GTP-bound RagB/RRAGB forms a complex with GDP-bound RagC/RRAGC (or RagD/RRAGD) and in an inactive form when GDP-bound RagB/RRAGB heterodimerizes with GTP-bound RagC/RRAGC (or RagD/RRAGD). In its GTP-bound active form, promotes the recruitment of mTORC1 to the lysosomes and its subsequent activation by the GTPase RHEB. Involved in the RCC1/Ran-GTPase pathway.
• KEGG Pathway:
  Autophagy - animal (hsa04140)
  mTOR sig.ling pathway (hsa04150)
  Shigellosis (hsa05131)
• Reactome Pathway:
  MTOR signalling (R-HSA-165159)
  mTORC1-mediated signalling (R-HSA-166208)
  Energy dependent regulation of mTOR by LKB1-AMPK (R-HSA-380972)
  TP53 Regulates Metabolic Genes (R-HSA-5628897)
  Regulation of PTEN gene transcription (R-HSA-8943724)
  Amino acids regulate mTORC1 (R-HSA-9639288)
  Macroautophagy (R-HSA-1632852)

Molecular Interaction Atlas (MIA) of This DOT

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the methylation of Ras-related GTP-binding protein B (RRAGB).	[1]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of Ras-related GTP-binding protein B (RRAGB).	[8]

6 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 GTP-binding protein B (RRAGB).	[2]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Ras-related GTP-binding protein B (RRAGB).	[3]
Doxorubicin	DMVP5YE	Approved	Doxorubicin increases the expression of Ras-related GTP-binding protein B (RRAGB).	[4]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of Ras-related GTP-binding protein B (RRAGB).	[5]
Rifampicin	DM5DSFZ	Approved	Rifampicin decreases the expression of Ras-related GTP-binding protein B (RRAGB).	[6]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of Ras-related GTP-binding protein B (RRAGB).	[7]

References

• [1] 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.
• [2] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [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] 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] Temozolomide induces activation of Wnt/-catenin signaling in glioma cells via PI3K/Akt pathway: implications in glioma therapy. Cell Biol Toxicol. 2020 Jun;36(3):273-278. doi: 10.1007/s10565-019-09502-7. Epub 2019 Nov 22.
• [6] Integrated analysis of rifampicin-induced microRNA and gene expression changes in human hepatocytes. Drug Metab Pharmacokinet. 2014;29(4):333-40.
• [7] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [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.