Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTJCW5ZD)

DOT Name Ral guanine nucleotide dissociation stimulator-like 2 (RGL2)
Synonyms RalGDS-like 2; RalGDS-like factor; Ras-associated protein RAB2L
Gene Name RGL2
Related Disease
Matthew-Wood syndrome ( )
Pancreatic cancer ( )
UniProt ID
RGL2_HUMAN
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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PDB ID
8AU4; 8B69
Pfam ID
PF00788 ; PF00617 ; PF00618
Sequence
MLPRPLRLLLDTSPPGGVVLSSFRSRDPEEGGGPGGLVVGGGQEEEEEEEEEAPVSVWDE
EEDGAVFTVTSRQYRPLDPLVPMPPPRSSRRLRAGTLEALVRHLLDTRTSGTDVSFMSAF
LATHRAFTSTPALLGLMADRLEALESHPTDELERTTEVAISVLSTWLASHPEDFGSEAKG
QLDRLESFLLQTGYAAGKGVGGGSADLIRNLRSRVDPQAPDLPKPLALPGDPPADPTDVL
VFLADHLAEQLTLLDAELFLNLIPSQCLGGLWGHRDRPGHSHLCPSVRATVTQFNKVAGA
VVSSVLGATSTGEGPGEVTIRPLRPPQRARLLEKWIRVAEECRLLRNFSSVYAVVSALQS
SPIHRLRAAWGEATRDSLRVFSSLCQIFSEEDNYSQSRELLVQEVKLQSPLEPHSKKAPR
SGSRGGGVVPYLGTFLKDLVMLDAASKDELENGYINFDKRRKEFAVLSELRRLQNECRGY
NLQPDHDIQRWLQGLRPLTEAQSHRVSCEVEPPGSSDPPAPRVLRPTLVISQWTEVLGSV
GVPTPLVSCDRPSTGGDEAPTTPAPLLTRLAQHMKWPSVSSLDSALESSPSLHSPADPSH
LSPPASSPRPSRGHRRSASCGSPLSGGAEEASGGTGYGGEGSGPGASDCRIIRVQMELGE
DGSVYKSILVTSQDKAPSVISRVLKKNNRDSAVASEYELVQLLPGERELTIPASANVFYA
MDGASHDFLLRQRRRSSTATPGVTSGPSASGTPPSEGGGGSFPRIKATGRKIARALF
Function Probable guanine nucleotide exchange factor. Putative effector of Ras and/or Rap. Associates with the GTP-bound form of Rap 1A and H-Ras in vitro.
KEGG Pathway
Ras sig.ling pathway (hsa04014 )
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
Matthew-Wood syndrome DISA7HR7 Strong Biomarker [1]
Pancreatic cancer DISJC981 Strong Altered Expression [1]
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Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
3 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 Ral guanine nucleotide dissociation stimulator-like 2 (RGL2). [2]
Arsenic DMTL2Y1 Approved Arsenic affects the methylation of Ral guanine nucleotide dissociation stimulator-like 2 (RGL2). [6]
PMID28870136-Compound-52 DMFDERP Patented PMID28870136-Compound-52 decreases the phosphorylation of Ral guanine nucleotide dissociation stimulator-like 2 (RGL2). [7]
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3 Drug(s) Affected the Gene/Protein Processing of This DOT
Drug Name Drug ID Highest Status Interaction REF
Tretinoin DM49DUI Approved Tretinoin increases the expression of Ral guanine nucleotide dissociation stimulator-like 2 (RGL2). [3]
Doxorubicin DMVP5YE Approved Doxorubicin increases the expression of Ral guanine nucleotide dissociation stimulator-like 2 (RGL2). [4]
Estradiol DMUNTE3 Approved Estradiol decreases the expression of Ral guanine nucleotide dissociation stimulator-like 2 (RGL2). [5]
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References

1 Aberrant overexpression of the Rgl2 Ral small GTPase-specific guanine nucleotide exchange factor promotes pancreatic cancer growth through Ral-dependent and Ral-independent mechanisms.J Biol Chem. 2010 Nov 5;285(45):34729-40. doi: 10.1074/jbc.M110.116756. Epub 2010 Aug 27.
2 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.
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 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 17-Estradiol Activates HSF1 via MAPK Signaling in ER-Positive Breast Cancer Cells. Cancers (Basel). 2019 Oct 11;11(10):1533. doi: 10.3390/cancers11101533.
6 Prenatal arsenic exposure and the epigenome: identifying sites of 5-methylcytosine alterations that predict functional changes in gene expression in newborn cord blood and subsequent birth outcomes. Toxicol Sci. 2015 Jan;143(1):97-106. doi: 10.1093/toxsci/kfu210. Epub 2014 Oct 10.
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.