Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTT6K1GE)

• DOT Name: Rab-interacting lysosomal protein (RILP)
• Gene Name: RILP
• Related Disease:
  Hepatitis C virus infection
  Cystinosis
  Ebola virus infection
• UniProt ID: RILP_HUMAN
• PDB ID: 1YHN
• Pfam ID: PF09744 ; PF11461
• Sequence:
  MEPRRAAPGVPGWGSREAAGSASAAELVYHLAGALGTELQDLARRFGPEAAAGLVPLVVR
  ALELLEQAAVGPAPDSLQVSAQPAEQELRRLREENERLRRELRAGPQEERALLRQLKEVT
  DRQRDELRAHNRDLRQRGQETEALQEQLQRLLLVNAELRHKLAAMQTQLRAAQDRERERQ
  QPGEAATPQAKERARGQAGRPGHQHGQEPEWATAGAGAPGNPEDPAEAAQQLGRPSEAGQ
  CRFSREEFEQILQERNELKAKVFLLKEELAYFQRELLTDHRVPGLLLEAMKVAVRKQRKK
  IKAKMLGTPEEAESSEDEAGPWILLSDDKGDHPPPPESKIQSFFGLWYRGKAESSEDETS
  SPAPSKLGGEEEAQPQSPAPDPPCSALHEHLCLGASAAPEA
• Function: Rab effector playing a role in late endocytic transport to degradative compartments. Involved in the regulation of lysosomal morphology and distribution. Induces recruitment of dynein-dynactin motor complexes to Rab7A-containing late endosome and lysosome compartments. Promotes centripetal migration of phagosomes and the fusion of phagosomes with the late endosomes and lysosomes.
• Tissue Specificity: Ubiquitous. Strongly expressed in fetal heart, heart, stomach, spleen, adrenal gland, thyroid gland, salivary gland, fetal liver, liver and lung. Poorly expressed in brain.
• KEGG Pathway:
  Phagosome (hsa04145)
  Salmonella infection (hsa05132)
• Reactome Pathway: MHC class II antigen presentation (R-HSA-2132295)

Molecular Interaction Atlas (MIA) of This DOT

3 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Hepatitis C virus infection	DISQ0M8R	Strong	Altered Expression	[1]
Cystinosis	DISXY3VI	Limited	Altered Expression	[2]
Ebola virus infection	DISJAVM1	Limited	Biomarker	[3]

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 Rab-interacting lysosomal protein (RILP).	[4]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of Rab-interacting lysosomal protein (RILP).	[11]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Rab-interacting lysosomal protein (RILP).	[5]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Rab-interacting lysosomal protein (RILP).	[6]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Rab-interacting lysosomal protein (RILP).	[7]
Triclosan	DMZUR4N	Approved	Triclosan decreases the expression of Rab-interacting lysosomal protein (RILP).	[8]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of Rab-interacting lysosomal protein (RILP).	[9]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Rab-interacting lysosomal protein (RILP).	[10]

References

• [1] Hepatitis C virus promotes virion secretion through cleavage of the Rab7 adaptor protein RILP.Proc Natl Acad Sci U S A. 2016 Nov 1;113(44):12484-12489. doi: 10.1073/pnas.1607277113. Epub 2016 Oct 17.
• [2] Cystinosin, the small GTPase Rab11, and the Rab7 effector RILP regulate intracellular trafficking of the chaperone-mediated autophagy receptor LAMP2A.J Biol Chem. 2017 Jun 23;292(25):10328-10346. doi: 10.1074/jbc.M116.764076. Epub 2017 May 2.
• [3] Late endosomal transport and tethering are coupled processes controlled by RILP and the cholesterol sensor ORP1L.J Cell Sci. 2013 Aug 1;126(Pt 15):3462-74. doi: 10.1242/jcs.129270. Epub 2013 May 31.
• [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] 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.
• [6] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [7] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [8] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [9] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [10] Definition of transcriptome-based indices for quantitative characterization of chemically disturbed stem cell development: introduction of the STOP-Toxukn and STOP-Toxukk tests. Arch Toxicol. 2017 Feb;91(2):839-864.
• [11] 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.