Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTUB8RLS)

• DOT Name: RELT-like protein 1 (RELL1)
• Gene Name: RELL1
• UniProt ID: RELL1_HUMAN
• Pfam ID: PF12606
• Sequence:
  MAPRALPGSAVLAAAVFVGGAVSSPLVAPDNGSSRTLHSRTETTPSPSNDTGNGHPEYIA
  YALVPVFFIMGLFGVLICHLLKKKGYRCTTEAEQDIEEEKVEKIELNDSVNENSDTVGQI
  VHYIMKNEANADVLKAMVADNSLYDPESPVTPSTPGSPPVSPGPLSPGGTPGKHVCGHHL
  HTVGGVVERDVCHRCRHKRWHFIKPTNKSRESRPRRQGEVTVLSVGRFRVTKVEHKSNQK
  ERRSLMSVSGAETVNGEVPATPVKRERSGTE
• Function: Induces activation of MAPK14/p38 cascade, when overexpressed. Induces apoptosis, when overexpressed.
• Tissue Specificity: Widely expressed. Expressed at highest levels in the placenta, skeletal muscle, spleen and testis.
• KEGG Pathway: Cytokine-cytokine receptor interaction (hsa04060)

Molecular Interaction Atlas (MIA) of This DOT

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the expression of RELT-like protein 1 (RELL1).	[1]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of RELT-like protein 1 (RELL1).	[2]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of RELT-like protein 1 (RELL1).	[3]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of RELT-like protein 1 (RELL1).	[4]
Doxorubicin	DMVP5YE	Approved	Doxorubicin increases the expression of RELT-like protein 1 (RELL1).	[5]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of RELT-like protein 1 (RELL1).	[8]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of RELT-like protein 1 (RELL1).	[9]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of RELT-like protein 1 (RELL1).	[6]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 affects the phosphorylation of RELT-like protein 1 (RELL1).	[7]

References

• [1] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [2] Comparison of HepG2 and HepaRG by whole-genome gene expression analysis for the purpose of chemical hazard identification. Toxicol Sci. 2010 May;115(1):66-79.
• [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] Gene expression analysis of precision-cut human liver slices indicates stable expression of ADME-Tox related genes. Toxicol Appl Pharmacol. 2011 May 15;253(1):57-69.
• [5] 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.
• [6] 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.
• [7] 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.
• [8] 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.
• [9] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.