General Information of Drug Off-Target (DOT) (ID: OTG36NI7)

DOT Name Ral guanine nucleotide dissociation stimulator (RALGDS)
Synonyms RalGDS; Ral guanine nucleotide exchange factor; RalGEF
Gene Name RALGDS
Related Disease
Advanced cancer ( )
Brain cancer ( )
Brain neoplasm ( )
Intellectual disability ( )
Medulloblastoma ( )
Melanoma ( )
Prostate cancer ( )
Prostate carcinoma ( )
Skin neoplasm ( )
Squamous cell carcinoma ( )
Matthew-Wood syndrome ( )
Pancreatic ductal carcinoma ( )
Amyotrophic lateral sclerosis type 4 ( )
Complex neurodevelopmental disorder ( )
Enterovirus infection ( )
Neoplasm ( )
UniProt ID
GNDS_HUMAN
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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PDB ID
1RAX; 2B3A; 2RGF; 3KH0
Pfam ID
PF00788 ; PF00617 ; PF00618
Sequence
MVQRMWAEAAGPAGGAEPLFPGSRRSRSVWDAVRLEVGVPDSCPVVLHSFTQLDPDLPRP
ESSTQEIGEELINGVIYSISLRKVQLHHGGNKGQRWLGYENESALNLYETCKVRTVKAGT
LEKLVEHLVPAFQGSDLSYVTIFLCTYRAFTTTQQVLDLLFKRYGRCDALTASSRYGCIL
PYSDEDGGPQDQLKNAISSILGTWLDQYSEDFCQPPDFPCLKQLVAYVQLNMPGSDLERR
AHLLLAQLEHSEPIEAEPEALSPVPALKPTPELELALTPARAPSPVPAPAPEPEPAPTPA
PGSELEVAPAPAPELQQAPEPAVGLESAPAPALELEPAPEQDPAPSQTLELEPAPAPVPS
LQPSWPSPVVAENGLSEEKPHLLVFPPDLVAEQFTLMDAELFKKVVPYHCLGSIWSQRDK
KGKEHLAPTIRATVTQFNSVANCVITTCLGNRSTKAPDRARVVEHWIEVARECRILKNFS
SLYAILSALQSNSIHRLKKTWEDVSRDSFRIFQKLSEIFSDENNYSLSRELLIKEGTSKF
ATLEMNPKRAQKRPKETGIIQGTVPYLGTFLTDLVMLDTAMKDYLYGRLINFEKRRKEFE
VIAQIKLLQSACNNYSIAPDEQFGAWFRAVERLSETESYNLSCELEPPSESASNTLRTKK
NTAIVKRWSDRQAPSTELSTSGSSHSKSCDQLRCGPYLSSGDIADALSVHSAGSSSSDVE
EINISFVPESPDGQEKKFWESASQSSPETSGISSASSSTSSSSASTTPVAATRTHKRSVS
GLCNSSSALPLYNQQVGDCCIIRVSLDVDNGNMYKSILVTSQDKAPAVIRKAMDKHNLEE
EEPEDYELLQILSDDRKLKIPENANVFYAMNSTANYDFVLKKRTFTKGVKVKHGASSTLP
RMKQKGLKIAKGIF
Function
Functions as a guanine nucleotide exchange factor (GEF) activating either RalA or RalB GTPases and plays an important role in intracellular transport. Interacts and acts as an effector molecule for R-Ras, H-Ras, K-Ras, and Rap. During bacterial clearance, recognizes 'Lys-33'-linked polyubiquitinated TRAF3 and subsequently mediates assembly of the exocyst complex.
KEGG Pathway
Ras sig.ling pathway (hsa04014 )
Rap1 sig.ling pathway (hsa04015 )
Phospholipase D sig.ling pathway (hsa04072 )
Pathways in cancer (hsa05200 )
Colorectal cancer (hsa05210 )
Pancreatic cancer (hsa05212 )
Choline metabolism in cancer (hsa05231 )
Reactome Pathway
RAF/MAP kinase cascade (R-HSA-5673001 )
p38MAPK events (R-HSA-171007 )

Molecular Interaction Atlas (MIA) of This DOT

16 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Advanced cancer DISAT1Z9 Strong Biomarker [1]
Brain cancer DISBKFB7 Strong Genetic Variation [2]
Brain neoplasm DISY3EKS Strong Genetic Variation [2]
Intellectual disability DISMBNXP Strong Biomarker [3]
Medulloblastoma DISZD2ZL Strong Genetic Variation [2]
Melanoma DIS1RRCY Strong Biomarker [4]
Prostate cancer DISF190Y Strong Biomarker [5]
Prostate carcinoma DISMJPLE Strong Biomarker [5]
Skin neoplasm DIS16DDV Strong Biomarker [6]
Squamous cell carcinoma DISQVIFL Strong Biomarker [7]
Matthew-Wood syndrome DISA7HR7 moderate Genetic Variation [8]
Pancreatic ductal carcinoma DIS26F9Q moderate Altered Expression [8]
Amyotrophic lateral sclerosis type 4 DISSDHYG Limited Biomarker [9]
Complex neurodevelopmental disorder DISB9AFI Limited Autosomal recessive [10]
Enterovirus infection DISH2UDP Limited Biomarker [11]
Neoplasm DISZKGEW Limited Biomarker [12]
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⏷ Show the Full List of 16 Disease(s)
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
13 Drug(s) Affected the Gene/Protein Processing of This DOT
Drug Name Drug ID Highest Status Interaction REF
Valproate DMCFE9I Approved Valproate affects the expression of Ral guanine nucleotide dissociation stimulator (RALGDS). [13]
Acetaminophen DMUIE76 Approved Acetaminophen decreases the expression of Ral guanine nucleotide dissociation stimulator (RALGDS). [15]
Doxorubicin DMVP5YE Approved Doxorubicin decreases the expression of Ral guanine nucleotide dissociation stimulator (RALGDS). [16]
Cisplatin DMRHGI9 Approved Cisplatin decreases the expression of Ral guanine nucleotide dissociation stimulator (RALGDS). [17]
Quercetin DM3NC4M Approved Quercetin increases the expression of Ral guanine nucleotide dissociation stimulator (RALGDS). [18]
Vorinostat DMWMPD4 Approved Vorinostat decreases the expression of Ral guanine nucleotide dissociation stimulator (RALGDS). [19]
Decitabine DMQL8XJ Approved Decitabine affects the expression of Ral guanine nucleotide dissociation stimulator (RALGDS). [20]
Demecolcine DMCZQGK Approved Demecolcine increases the expression of Ral guanine nucleotide dissociation stimulator (RALGDS). [21]
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene increases the expression of Ral guanine nucleotide dissociation stimulator (RALGDS). [22]
Formaldehyde DM7Q6M0 Investigative Formaldehyde increases the expression of Ral guanine nucleotide dissociation stimulator (RALGDS). [21]
Milchsaure DM462BT Investigative Milchsaure increases the expression of Ral guanine nucleotide dissociation stimulator (RALGDS). [23]
Deguelin DMXT7WG Investigative Deguelin decreases the expression of Ral guanine nucleotide dissociation stimulator (RALGDS). [24]
4-hydroxy-2-nonenal DM2LJFZ Investigative 4-hydroxy-2-nonenal decreases the expression of Ral guanine nucleotide dissociation stimulator (RALGDS). [25]
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⏷ Show the Full List of 13 Drug(s)
1 Drug(s) Affected the Post-Translational Modifications of This DOT
Drug Name Drug ID Highest Status Interaction REF
Ciclosporin DMAZJFX Approved Ciclosporin decreases the methylation of Ral guanine nucleotide dissociation stimulator (RALGDS). [14]
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References

1 Tumour prevention by a single antibody domain targeting the interaction of signal transduction proteins with RAS.EMBO J. 2007 Jul 11;26(13):3250-9. doi: 10.1038/sj.emboj.7601744. Epub 2007 Jun 14.
2 Implementation of a High-Throughput Pilot Screen in Peptide Hydrogel-Based Three-Dimensional Cell Cultures.SLAS Discov. 2019 Aug;24(7):714-723. doi: 10.1177/2472555219844570. Epub 2019 Apr 30.
3 Deep sequencing reveals 50 novel genes for recessive cognitive disorders. Nature. 2011 Sep 21;478(7367):57-63. doi: 10.1038/nature10423.
4 No evidence of RALGDS mutations in cutaneous melanoma.Melanoma Res. 2007 Dec;17(6):410-2. doi: 10.1097/CMR.0b013e3282ef4178.
5 MAZ promotes prostate cancer bone metastasis through transcriptionally activating the KRas-dependent RalGEFs pathway.J Exp Clin Cancer Res. 2019 Sep 5;38(1):391. doi: 10.1186/s13046-019-1374-x.
6 RalGDS is required for tumor formation in a model of skin carcinogenesis.Cancer Cell. 2005 Mar;7(3):219-26. doi: 10.1016/j.ccr.2005.01.029.
7 The human Rgr oncogene is overexpressed in T-cell malignancies and induces transformation by acting as a GEF for Ras and Ral.Oncogene. 2011 Aug 25;30(34):3661-71. doi: 10.1038/onc.2011.93. Epub 2011 Mar 28.
8 Response to MLN8237 in pancreatic cancer is not dependent on RalA phosphorylation.Mol Cancer Ther. 2014 Jan;13(1):122-33. doi: 10.1158/1535-7163.MCT-12-1232. Epub 2013 Nov 12.
9 A gene for autosomal dominant juvenile amyotrophic lateral sclerosis (ALS4) localizes to a 500-kb interval on chromosome 9q34.Neurogenetics. 2000 Sep;3(1):1-6. doi: 10.1007/pl00022976.
10 Classification of Genes: Standardized Clinical Validity Assessment of Gene-Disease Associations Aids Diagnostic Exome Analysis and Reclassifications. Hum Mutat. 2017 May;38(5):600-608. doi: 10.1002/humu.23183. Epub 2017 Feb 13.
11 Fibronectin Facilitates Enterovirus 71 Infection by Mediating Viral Entry.J Virol. 2018 Apr 13;92(9):e02251-17. doi: 10.1128/JVI.02251-17. Print 2018 May 1.
12 Multifunctional Peptide-Amphiphile End-Capped Mesoporous Silica Nanoparticles for Tumor Targeting Drug Delivery.ACS Appl Mater Interfaces. 2017 Jan 25;9(3):2093-2103. doi: 10.1021/acsami.6b12647. Epub 2017 Jan 12.
13 Gene Expression Regulation and Pathway Analysis After Valproic Acid and Carbamazepine Exposure in a Human Embryonic Stem Cell-Based Neurodevelopmental Toxicity Assay. Toxicol Sci. 2015 Aug;146(2):311-20. doi: 10.1093/toxsci/kfv094. Epub 2015 May 15.
14 Integrative "-Omics" analysis in primary human hepatocytes unravels persistent mechanisms of cyclosporine A-induced cholestasis. Chem Res Toxicol. 2016 Dec 19;29(12):2164-2174.
15 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.
16 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.
17 Low doses of cisplatin induce gene alterations, cell cycle arrest, and apoptosis in human promyelocytic leukemia cells. Biomark Insights. 2016 Aug 24;11:113-21.
18 Comparison of phenotypic and transcriptomic effects of false-positive genotoxins, true genotoxins and non-genotoxins using HepG2 cells. Mutagenesis. 2011 Sep;26(5):593-604.
19 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.
20 Epigenetic silencing of novel tumor suppressors in malignant melanoma. Cancer Res. 2006 Dec 1;66(23):11187-93. doi: 10.1158/0008-5472.CAN-06-1274.
21 Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
22 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.
23 Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.
24 Neurotoxicity and underlying cellular changes of 21 mitochondrial respiratory chain inhibitors. Arch Toxicol. 2021 Feb;95(2):591-615. doi: 10.1007/s00204-020-02970-5. Epub 2021 Jan 29.
25 Microarray analysis of H2O2-, HNE-, or tBH-treated ARPE-19 cells. Free Radic Biol Med. 2002 Nov 15;33(10):1419-32.