Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT5Z6F8O)

DOT Name Ras and Rab interactor 3 (RIN3)
Synonyms Ras interaction/interference protein 3
Gene Name RIN3
Related Disease
Alzheimer disease ( )
Bone Paget disease ( )
Dementia ( )
Obesity ( )
Paget's disease ( )
Vascular dementia ( )
UniProt ID
RIN3_HUMAN
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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PDB ID
3U23; 4WCI
Pfam ID
PF02204
Sequence
MIRHAGAPARGDPTGPVPVVGKGEEEEEEDGMRLCLPANPKNCLPHRRGISILEKLIKTC
PVWLQLSLGQAEVARILHRVVAGMFLVRRDSSSKQLVLCVHFPSLNESSAEVLEYTIKEE
KSILYLEGSALVFEDIFRLIAFYCVSRDLLPFTLRLPQAILEASSFTDLETIANLGLGFW
DSSLNPPQERGKPAEPPRDRAPGFPLVSSLRPTAHDANCACEIELSVGNDRLWFVNPIFI
EDCSSALPTDQPPLGNCPARPLPPTSDATSPTSRWAPRRPPPPPPVLPLQPCSPAQPPVL
PALAPAPACPLPTSPPVPAPHVTPHAPGPPDHPNQPPMMTCERLPCPTAGLGPLREEAMK
PGAASSPLQQVPAPPLPAKKNLPTAPPRRRVSERVSLEDQSPGMAAEGDQLSLPPQGTSD
GPEDTPRESTEQGQDTEVKASDPHSMPELPRTAKQPPVPPPRKKRISRQLASTLPAPLEN
AELCTQAMALETPTPGPPREGQSPASQAGTQHPPAQATAHSQSSPEFKGSLASLSDSLGV
SVMATDQDSYSTSSTEEELEQFSSPSVKKKPSMILGKARHRLSFASFSSMFHAFLSNNRK
LYKKVVELAQDKGSYFGSLVQDYKVYSLEMMARQTSSTEMLQEIRTMMTQLKSYLLQSTE
LKALVDPALHSEEELEAIVESALYKCVLKPLKEAINSCLHQIHSKDGSLQQLKENQLVIL
ATTTTDLGVTTSVPEVPMMEKILQKFTSMHKAYSPEKKISILLKTCKLIYDSMALGNPGK
PYGADDFLPVLMYVLARSNLTEMLLNVEYMMELMDPALQLGEGSYYLTTTYGALEHIKSY
DKITVTRQLSVEVQDSIHRWERRRTLNKARASRSSVQDFICVSYLEPEQQARTLASRADT
QAQALCAQCAEKFAVERPQAHRLFVLVDGRCFQLADDALPHCIKGYLLRSEPKRDFHFVY
RPLDGGGGGGGGSPPCLVVREPNFL
Function Ras effector protein that functions as a guanine nucleotide exchange (GEF) for RAB5B and RAB31, by exchanging bound GDP for free GTP. Required for normal RAB31 function.
Tissue Specificity Widely expressed.
Reactome Pathway
RAB GEFs exchange GTP for GDP on RABs (R-HSA-8876198 )

Molecular Interaction Atlas (MIA) of This DOT

6 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Alzheimer disease DISF8S70 Strong Genetic Variation [1]
Bone Paget disease DISIPS4V Strong Genetic Variation [2]
Dementia DISXL1WY Strong Biomarker [1]
Obesity DIS47Y1K Strong Genetic Variation [3]
Paget's disease DISO3MC0 Strong Genetic Variation [4]
Vascular dementia DISVO82H Strong Biomarker [1]
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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
2 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 Ras and Rab interactor 3 (RIN3). [5]
PMID28870136-Compound-52 DMFDERP Patented PMID28870136-Compound-52 decreases the phosphorylation of Ras and Rab interactor 3 (RIN3). [16]
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12 Drug(s) Affected the Gene/Protein Processing of This DOT
Drug Name Drug ID Highest Status Interaction REF
Ciclosporin DMAZJFX Approved Ciclosporin increases the expression of Ras and Rab interactor 3 (RIN3). [6]
Tretinoin DM49DUI Approved Tretinoin increases the expression of Ras and Rab interactor 3 (RIN3). [7]
Cupric Sulfate DMP0NFQ Approved Cupric Sulfate decreases the expression of Ras and Rab interactor 3 (RIN3). [8]
Estradiol DMUNTE3 Approved Estradiol increases the expression of Ras and Rab interactor 3 (RIN3). [9]
Calcitriol DM8ZVJ7 Approved Calcitriol increases the expression of Ras and Rab interactor 3 (RIN3). [10]
Testosterone DM7HUNW Approved Testosterone increases the expression of Ras and Rab interactor 3 (RIN3). [10]
Methotrexate DM2TEOL Approved Methotrexate decreases the expression of Ras and Rab interactor 3 (RIN3). [11]
Urethane DM7NSI0 Phase 4 Urethane decreases the expression of Ras and Rab interactor 3 (RIN3). [12]
Amiodarone DMUTEX3 Phase 2/3 Trial Amiodarone increases the expression of Ras and Rab interactor 3 (RIN3). [13]
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene increases the mutagenesis of Ras and Rab interactor 3 (RIN3). [14]
(+)-JQ1 DM1CZSJ Phase 1 (+)-JQ1 decreases the expression of Ras and Rab interactor 3 (RIN3). [15]
Bisphenol A DM2ZLD7 Investigative Bisphenol A increases the expression of Ras and Rab interactor 3 (RIN3). [17]
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⏷ Show the Full List of 12 Drug(s)

References

1 Blood-brain barrier transcytosis genes, risk of dementia and stroke: a prospective cohort study of 74,754 individuals.Eur J Epidemiol. 2019 Jun;34(6):579-590. doi: 10.1007/s10654-019-00498-2. Epub 2019 Mar 4.
2 Genetic Variation in RIN3 in the Belgian Population Supports Its Involvement in the Pathogenesis of Paget's Disease of Bone and Modifies the Age of Onset.Calcif Tissue Int. 2019 Jun;104(6):613-621. doi: 10.1007/s00223-019-00530-3. Epub 2019 Feb 6.
3 Identification of rs7350481 at chromosome 11q23.3 as a novel susceptibility locus for metabolic syndrome in Japanese individuals by an exome-wide association study.Oncotarget. 2017 Jun 13;8(24):39296-39308. doi: 10.18632/oncotarget.16945.
4 Targeted sequencing of the Paget's disease associated 14q32 locus identifies several missense coding variants in RIN3 that predispose to Paget's disease of bone.Hum Mol Genet. 2015 Jun 1;24(11):3286-95. doi: 10.1093/hmg/ddv068. Epub 2015 Feb 20.
5 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.
6 Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
7 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.
8 Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
9 Genistein and bisphenol A exposure cause estrogen receptor 1 to bind thousands of sites in a cell type-specific manner. Genome Res. 2012 Nov;22(11):2153-62.
10 Effects of 1alpha,25 dihydroxyvitamin D3 and testosterone on miRNA and mRNA expression in LNCaP cells. Mol Cancer. 2011 May 18;10:58.
11 Global molecular effects of tocilizumab therapy in rheumatoid arthritis synovium. Arthritis Rheumatol. 2014 Jan;66(1):15-23.
12 Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
13 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.
14 Exome-wide mutation profile in benzo[a]pyrene-derived post-stasis and immortal human mammary epithelial cells. Mutat Res Genet Toxicol Environ Mutagen. 2014 Dec;775-776:48-54. doi: 10.1016/j.mrgentox.2014.10.011. Epub 2014 Nov 4.
15 Bromodomain-containing protein 4 (BRD4) regulates RNA polymerase II serine 2 phosphorylation in human CD4+ T cells. J Biol Chem. 2012 Dec 14;287(51):43137-55.
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 Characterization of the Molecular Alterations Induced by the Prolonged Exposure of Normal Colon Mucosa and Colon Cancer Cells to Low-Dose Bisphenol A. Int J Mol Sci. 2022 Oct 1;23(19):11620. doi: 10.3390/ijms231911620.