Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTWZ30EZ)

DOT Name Ral guanine nucleotide dissociation stimulator-like 3 (RGL3)
Synonyms RalGDS-like 3
Gene Name RGL3
Related Disease
Cardiovascular disease ( )
High blood pressure ( )
UniProt ID
RGL3_HUMAN
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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Pfam ID
PF00788 ; PF00617 ; PF00618
Sequence
MERTAGKELALAPLQDWGEETEDGAVYSVSLRRQRSQRRSPAEGPGGSQAPSPIANTFLH
YRTSKVRVLRAARLERLVGELVFGDREQDPSFMPAFLATYRTFVPTACLLGFLLPPMPPP
PPPGVEIKKTAVQDLSFNKNLRAVVSVLGSWLQDHPQDFRDHPAHSDLGSVRTFLGWAAP
GSAEAQKAEKLLEDFLEEAEREQEEEPPQVWTGPPRVAQTSDPDSSEACAEEEEGLMPQG
PQLLDFSVDEVAEQLTLIDLELFSKVRLYECLGSVWSQRDRPGAAGASPTVRATVAQFNT
VTGCVLGSVLGAPGLAAPQRAQRLEKWIRIAQRCRELRNFSSLRAILSALQSNPIYRLKR
SWGAVSREPLSTFRKLSQIFSDENNHLSSREILFQEEATEGSQEEDNTPGSLPSKPPPGP
VPYLGTFLTDLVMLDTALPDMLEGDLINFEKRRKEWEILARIQQLQRRCQSYTLSPHPPI
LAALHAQNQLTEEQSYRLSRVIEPPAASCPSSPRIRRRISLTKRLSAKLAREKSSSPSGS
PGDPSSPTSSVSPGSPPSSPRSRDAPAGSPPASPGPQGPSTKLPLSLDLPSPRPFALPLG
SPRIPLPAQQSSEARVIRVSIDNDHGNLYRSILLTSQDKAPSVVRRALQKHNVPQPWACD
YQLFQVLPGDRVLLIPDNANVFYAMSPVAPRDFMLRRKEGTRNTLSVSPS
Function Guanine nucleotide exchange factor (GEF) for Ral-A. Potential effector of GTPase HRas and Ras-related protein M-Ras. Negatively regulates Elk-1-dependent gene induction downstream of HRas and MEKK1.
Reactome Pathway
RAF/MAP kinase cascade (R-HSA-5673001 )

Molecular Interaction Atlas (MIA) of This DOT

2 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Cardiovascular disease DIS2IQDX Strong Genetic Variation [1]
High blood pressure DISY2OHH Strong Genetic Variation [2]
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Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
6 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 Ral guanine nucleotide dissociation stimulator-like 3 (RGL3). [3]
Tretinoin DM49DUI Approved Tretinoin increases the expression of Ral guanine nucleotide dissociation stimulator-like 3 (RGL3). [4]
Testosterone DM7HUNW Approved Testosterone increases the expression of Ral guanine nucleotide dissociation stimulator-like 3 (RGL3). [6]
Triclosan DMZUR4N Approved Triclosan decreases the expression of Ral guanine nucleotide dissociation stimulator-like 3 (RGL3). [7]
SNDX-275 DMH7W9X Phase 3 SNDX-275 increases the expression of Ral guanine nucleotide dissociation stimulator-like 3 (RGL3). [3]
PMID28460551-Compound-2 DM4DOUB Patented PMID28460551-Compound-2 increases the expression of Ral guanine nucleotide dissociation stimulator-like 3 (RGL3). [9]
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⏷ Show the Full List of 6 Drug(s)
4 Drug(s) Affected the Post-Translational Modifications of This DOT
Drug Name Drug ID Highest Status Interaction REF
Arsenic DMTL2Y1 Approved Arsenic increases the methylation of Ral guanine nucleotide dissociation stimulator-like 3 (RGL3). [5]
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene increases the methylation of Ral guanine nucleotide dissociation stimulator-like 3 (RGL3). [8]
PMID28870136-Compound-52 DMFDERP Patented PMID28870136-Compound-52 affects the phosphorylation of Ral guanine nucleotide dissociation stimulator-like 3 (RGL3). [10]
Bisphenol A DM2ZLD7 Investigative Bisphenol A decreases the methylation of Ral guanine nucleotide dissociation stimulator-like 3 (RGL3). [11]
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References

1 Leveraging Polygenic Functional Enrichment to Improve GWAS Power.Am J Hum Genet. 2019 Jan 3;104(1):65-75. doi: 10.1016/j.ajhg.2018.11.008. Epub 2018 Dec 27.
2 Meta-analysis identifies common and rare variants influencing blood pressure and overlapping with metabolic trait loci.Nat Genet. 2016 Oct;48(10):1162-70. doi: 10.1038/ng.3660. Epub 2016 Sep 12.
3 A transcriptome-based classifier to identify developmental toxicants by stem cell testing: design, validation and optimization for histone deacetylase inhibitors. Arch Toxicol. 2015 Sep;89(9):1599-618.
4 Development of a neural teratogenicity test based on human embryonic stem cells: response to retinoic acid exposure. Toxicol Sci. 2011 Dec;124(2):370-7.
5 Effect of prenatal arsenic exposure on DNA methylation and leukocyte subpopulations in cord blood. Epigenetics. 2014 May;9(5):774-82. doi: 10.4161/epi.28153. Epub 2014 Feb 13.
6 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.
7 Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
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.
9 Cell-based two-dimensional morphological assessment system to predict cancer drug-induced cardiotoxicity using human induced pluripotent stem cell-derived cardiomyocytes. Toxicol Appl Pharmacol. 2019 Nov 15;383:114761. doi: 10.1016/j.taap.2019.114761. Epub 2019 Sep 15.
10 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.
11 DNA methylome-wide alterations associated with estrogen receptor-dependent effects of bisphenols in breast cancer. Clin Epigenetics. 2019 Oct 10;11(1):138. doi: 10.1186/s13148-019-0725-y.