Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTZ0NDKE)

• DOT Name: Ras and Rab interactor-like protein (RINL)
• Gene Name: RINL
• UniProt ID: RINL_HUMAN
• Pfam ID: PF02204
• Sequence:
  MAQPEDKAPEVPTEGVRLVPPQVNKADRTPLGVLSTLEPLTRLQRTWGVWHVPELDTQDA
  EALVGLWPLGSFLVTGRDPSQALVLRSGPLPGEVNTYQIQKIPRGVSLESSNLCMPDLPH
  LLAFLSASRDVLPRTLLLPPPTLGPRDEHTDPVQIGRVQQDTPGKVLSIVNQLYLETHRG
  WGREQTPQETEPEAAQRHDPAPRNPAPHGVSWVKGPLSPEVDHPGPALASLLEEEEEDLE
  GKEEGREDDPEEEGPEDVLTIHVQSLVRARSSYVARQYRSLRVRIASDSGGPHGSGDPAT
  ELLQDVRHLLTDLQDHLAKDSYIRAVFGSRGPGLPKKDEDPGPALETAVCQAVLAPLKPA
  LWTRLRTLRAPELRRLRRRQTALRAGAGPPGAQGPGPEGQSPAPALRSRIHERLAHLHAA
  CAPRRKVALLLEVCRDVYAGLARGENQDPLGADAFLPALTEELIWSPDIGDTQLDVEFLM
  ELLDPDELRGEAGYYLTTWFGALHHIAHYQPETDRAPRGLSSEARASLHQWHRRRTLHRK
  DHPRAQANLPFKEPWAEETVTGTSDN
• Function: Guanine nucleotide exchange factor (GEF) for RAB5A and RAB22A that activates RAB5A and RAB22A by exchanging bound GDP for free GTP. Plays a role in endocytosis via its role in activating Rab family members.
• Reactome Pathway: RAB GEFs exchange GTP for GDP on RABs (R-HSA-8876198)

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 increases the methylation of Ras and Rab interactor-like protein (RINL).	[1]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 decreases the phosphorylation of Ras and Rab interactor-like protein (RINL).	[9]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Ras and Rab interactor-like protein (RINL).	[2]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Ras and Rab interactor-like protein (RINL).	[3]
Testosterone	DM7HUNW	Approved	Testosterone increases the expression of Ras and Rab interactor-like protein (RINL).	[4]
Troglitazone	DM3VFPD	Approved	Troglitazone increases the expression of Ras and Rab interactor-like protein (RINL).	[5]
Rosiglitazone	DMILWZR	Approved	Rosiglitazone increases the expression of Ras and Rab interactor-like protein (RINL).	[5]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Ras and Rab interactor-like protein (RINL).	[6]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of Ras and Rab interactor-like protein (RINL).	[7]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Ras and Rab interactor-like protein (RINL).	[8]
Sulforaphane	DMQY3L0	Investigative	Sulforaphane decreases the expression of Ras and Rab interactor-like protein (RINL).	[10]

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] Predictive toxicology using systemic biology and liver microfluidic "on chip" approaches: application to acetaminophen injury. Toxicol Appl Pharmacol. 2012 Mar 15;259(3):270-80.
• [3] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [4] 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.
• [5] Transcriptomic analysis of untreated and drug-treated differentiated HepaRG cells over a 2-week period. Toxicol In Vitro. 2015 Dec 25;30(1 Pt A):27-35.
• [6] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [7] Identification of a transcriptomic signature of food-relevant genotoxins in human HepaRG hepatocarcinoma cells. Food Chem Toxicol. 2020 Jun;140:111297. doi: 10.1016/j.fct.2020.111297. Epub 2020 Mar 28.
• [8] Bromodomain-containing protein 4 (BRD4) regulates RNA polymerase II serine 2 phosphorylation in human CD4+ T cells. J Biol Chem. 2012 Dec 14;287(51):43137-55.
• [9] Quantitative phosphoproteomics reveal cellular responses from caffeine, coumarin and quercetin in treated HepG2 cells. Toxicol Appl Pharmacol. 2022 Aug 15;449:116110. doi: 10.1016/j.taap.2022.116110. Epub 2022 Jun 7.
• [10] Transcriptome and DNA methylation changes modulated by sulforaphane induce cell cycle arrest, apoptosis, DNA damage, and suppression of proliferation in human liver cancer cells. Food Chem Toxicol. 2020 Feb;136:111047. doi: 10.1016/j.fct.2019.111047. Epub 2019 Dec 12.