Details of Drug Off-Target (DOT)

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

DOT Name Rho guanine nucleotide exchange factor 10-like protein (ARHGEF10L)
Synonyms GrinchGEF
Gene Name ARHGEF10L
Related Disease
Epithelial ovarian cancer ( )
Hepatocellular carcinoma ( )
Bipolar disorder ( )
Schizoaffective disorder ( )
Schizophrenia ( )
Acute myelogenous leukaemia ( )
UniProt ID
ARGAL_HUMAN
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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Pfam ID
PF19057 ; PF00621 ; PF19056
Sequence
MASSNPPPQPAIGDQLVPGVPGPSSEAEDDPGEAFEFDDSDDEEDTSAALGVPSLAPERD
TDPPLIHLDSIPVTDPDPAAAPPGTGVPAWVSNGDAADAAFSGARHSSWKRKSSRRIDRF
TFPALEEDVIYDDVPCESPDAHQPGAERNLLYEDAHRAGAPRQAEDLGWSSSEFESYSED
SGEEAKPEVEVEPAKHRVSFQPKLSPDLTRLKERYARTKRDILALRVGGRDMQELKHKYD
CKMTQLMKAAKSGTKDGLEKTRMAVMRKVSFLHRKDVLGDSEEEDMGLLEVSVSDIKPPA
PELGPMPEGLSPQQVVRRHILGSIVQSEGSYVESLKRILQDYRNPLMEMEPKALSARKCQ
VVFFRVKEILHCHSMFQIALSSRVAEWDSTEKIGDLFVASFSKSMVLDVYSDYVNNFTSA
MSIIKKACLTKPAFLEFLKRRQVCSPDRVTLYGLMVKPIQRFPQFILLLQDMLKNTPRGH
PDRLSLQLALTELETLAEKLNEQKRLADQVAEIQQLTKSVSDRSSLNKLLTSGQRQLLLC
ETLTETVYGDRGQLIKSKERRVFLLNDMLVCANINFKPANHRGQLEISSLVPLGPKYVVK
WNTALPQVQVVEVGQDGGTYDKDNVLIQHSGAKKASASGQAQNKVYLGPPRLFQELQDLQ
KDLAVVEQITLLISTLHGTYQNLNMTVAQDWCLALQRLMRVKEEEIHSANKCRLRLLLPG
KPDKSGRPISFMVVFITPNPLSKISWVNRLHLAKIGLREENQPGWLCPDEDKKSKAPFWC
PILACCIPAFSSRALSLQLGALVHSPVNCPLLGFSAVSTSLPQGYLWVGGGQEGAGGQVE
IFSLNRPSPRTVKSFPLAAPVLCMEYIPELEEEAESRDESPTVADPSATVHPTICLGLQD
GSILLYSSVDTGTQCLVSCRSPGLQPVLCLRHSPFHLLAGLQDGTLAAYPRTSGGVLWDL
ESPPVCLTVGPGPVRTLLSLEDAVWASCGPRVTVLEATTLQPQQSFEAHQDEAVSVTHMV
KAGSGVWMAFSSGTSIRLFHTETLEHLQEINIATRTTFLLPGQKHLCVTSLLICQGLLWV
GTDQGVIVLLPVPRLEGIPKITGKGMVSLNGHCGPVAFLAVATSILAPDILRSDQEEAEG
PRAEEDKPDGQAHEPMPDSHVGRELTRKKGILLQYRLRSTAHLPGPLLSMREPAPADGAA
LEHSEEDGSIYEMADDPDIWVRSRPCARDAHRKEICSVAIISGGQGYRNFGSALGSSGRQ
APCGETDSTLLIWQVPLML
Function Acts as a guanine nucleotide exchange factor (GEF) for RHOA, RHOB and RHOC.
Tissue Specificity Detected in heart, liver, skeletal muscle, kidney and pancreas.
Reactome Pathway
G alpha (12/13) signalling events (R-HSA-416482 )
RHOA GTPase cycle (R-HSA-8980692 )
RHOB GTPase cycle (R-HSA-9013026 )
RHOC GTPase cycle (R-HSA-9013106 )
NRAGE signals death through JNK (R-HSA-193648 )

Molecular Interaction Atlas (MIA) of This DOT

6 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Epithelial ovarian cancer DIS56MH2 Strong Genetic Variation [1]
Hepatocellular carcinoma DIS0J828 Strong Altered Expression [2]
Bipolar disorder DISAM7J2 moderate Genetic Variation [3]
Schizoaffective disorder DISLBW6B moderate Genetic Variation [3]
Schizophrenia DISSRV2N moderate Genetic Variation [3]
Acute myelogenous leukaemia DISCSPTN Limited Genetic Variation [4]
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⏷ Show the Full List of 6 Disease(s)
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
10 Drug(s) Affected the Gene/Protein Processing of This DOT
Drug Name Drug ID Highest Status Interaction REF
Valproate DMCFE9I Approved Valproate decreases the expression of Rho guanine nucleotide exchange factor 10-like protein (ARHGEF10L). [5]
Ciclosporin DMAZJFX Approved Ciclosporin decreases the expression of Rho guanine nucleotide exchange factor 10-like protein (ARHGEF10L). [6]
Tretinoin DM49DUI Approved Tretinoin increases the expression of Rho guanine nucleotide exchange factor 10-like protein (ARHGEF10L). [7]
Acetaminophen DMUIE76 Approved Acetaminophen decreases the expression of Rho guanine nucleotide exchange factor 10-like protein (ARHGEF10L). [8]
Doxorubicin DMVP5YE Approved Doxorubicin decreases the expression of Rho guanine nucleotide exchange factor 10-like protein (ARHGEF10L). [9]
Cupric Sulfate DMP0NFQ Approved Cupric Sulfate decreases the expression of Rho guanine nucleotide exchange factor 10-like protein (ARHGEF10L). [10]
Vorinostat DMWMPD4 Approved Vorinostat decreases the expression of Rho guanine nucleotide exchange factor 10-like protein (ARHGEF10L). [12]
Carbamazepine DMZOLBI Approved Carbamazepine affects the expression of Rho guanine nucleotide exchange factor 10-like protein (ARHGEF10L). [13]
Amiodarone DMUTEX3 Phase 2/3 Trial Amiodarone increases the expression of Rho guanine nucleotide exchange factor 10-like protein (ARHGEF10L). [14]
Milchsaure DM462BT Investigative Milchsaure decreases the expression of Rho guanine nucleotide exchange factor 10-like protein (ARHGEF10L). [18]
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⏷ Show the Full List of 10 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 affects the methylation of Rho guanine nucleotide exchange factor 10-like protein (ARHGEF10L). [11]
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene decreases the methylation of Rho guanine nucleotide exchange factor 10-like protein (ARHGEF10L). [15]
PMID28870136-Compound-52 DMFDERP Patented PMID28870136-Compound-52 affects the phosphorylation of Rho guanine nucleotide exchange factor 10-like protein (ARHGEF10L). [16]
Bisphenol A DM2ZLD7 Investigative Bisphenol A decreases the methylation of Rho guanine nucleotide exchange factor 10-like protein (ARHGEF10L). [17]
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References

1 Variants in genes encoding small GTPases and association with epithelial ovarian cancer susceptibility.PLoS One. 2018 Jul 6;13(7):e0197561. doi: 10.1371/journal.pone.0197561. eCollection 2018.
2 ARHGEF10L contributes to liver tumorigenesis through RhoA-ROCK1 signaling and the epithelial-mesenchymal transition.Exp Cell Res. 2019 Jan 1;374(1):46-68. doi: 10.1016/j.yexcr.2018.11.007. Epub 2018 Nov 13.
3 Genome-wide association studies of smooth pursuit and antisaccade eye movements in psychotic disorders: findings from the B-SNIP study.Transl Psychiatry. 2017 Oct 24;7(10):e1249. doi: 10.1038/tp.2017.210.
4 Genome-wide haplotype association study identify the FGFR2 gene as a risk gene for acute myeloid leukemia.Oncotarget. 2017 Jan 31;8(5):7891-7899. doi: 10.18632/oncotarget.13631.
5 Stem cell transcriptome responses and corresponding biomarkers that indicate the transition from adaptive responses to cytotoxicity. Chem Res Toxicol. 2017 Apr 17;30(4):905-922.
6 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.
7 Retinoic acid receptor alpha amplifications and retinoic acid sensitivity in breast cancers. Clin Breast Cancer. 2013 Oct;13(5):401-8.
8 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.
9 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.
10 Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
11 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.
12 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.
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 Identification by automated screening of a small molecule that selectively eliminates neural stem cells derived from hESCs but not dopamine neurons. PLoS One. 2009 Sep 23;4(9):e7155.
15 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.
16 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.
17 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.
18 Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.