Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTFR2KM4)

DOT Name Ras-related protein Rab-5A (RAB5A)
Synonyms EC 3.6.5.2
Gene Name RAB5A
Related Disease
Brucellosis ( )
Advanced cancer ( )
Breast cancer ( )
Breast carcinoma ( )
Breast neoplasm ( )
Bronchitis ( )
Cervical cancer ( )
Cervical carcinoma ( )
Cervical Intraepithelial neoplasia ( )
Colorectal carcinoma ( )
Glioma ( )
Hepatitis B virus infection ( )
Hepatitis C virus infection ( )
Hepatocellular carcinoma ( )
Influenza ( )
Lyme disease ( )
Matthew-Wood syndrome ( )
Metastatic malignant neoplasm ( )
Motor neurone disease ( )
Myocardial ischemia ( )
Nephrotic syndrome ( )
Non-alcoholic steatohepatitis ( )
Oculocerebrorenal syndrome ( )
Renal cell carcinoma ( )
Triple negative breast cancer ( )
Amyotrophic lateral sclerosis ( )
Rabies ( )
Alzheimer disease ( )
Asthma ( )
Epithelial ovarian cancer ( )
Lung adenocarcinoma ( )
Lung cancer ( )
Lung carcinoma ( )
Melanoma ( )
Neoplasm ( )
Nervous system inflammation ( )
Non-small-cell lung cancer ( )
Ovarian cancer ( )
Ovarian neoplasm ( )
Pancreatic cancer ( )
Prostate cancer ( )
Prostate carcinoma ( )
UniProt ID
RAB5A_HUMAN
3D Structure
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2D Sequence (FASTA)
Download
3D Structure (PDB)
Download
PDB ID
1N6H; 1N6I; 1N6K; 1N6L; 1N6N; 1N6O; 1N6P; 1N6R; 1R2Q; 1TU3; 1TU4; 3MJH; 4Q9U; 7BL1
EC Number
3.6.5.2
Pfam ID
PF00071
Sequence
MASRGATRPNGPNTGNKICQFKLVLLGESAVGKSSLVLRFVKGQFHEFQESTIGAAFLTQ
TVCLDDTTVKFEIWDTAGQERYHSLAPMYYRGAQAAIVVYDITNEESFARAKNWVKELQR
QASPNIVIALSGNKADLANKRAVDFQEAQSYADDNSLLFMETSAKTSMNVNEIFMAIAKK
LPKNEPQNPGANSARGRGVDLTEPTQPTRNQCCSN
Function
Small GTPase which cycles between active GTP-bound and inactive GDP-bound states. In its active state, binds to a variety of effector proteins to regulate cellular responses such as of intracellular membrane trafficking, from the formation of transport vesicles to their fusion with membranes. Active GTP-bound form is able to recruit to membranes different sets of downstream effectors directly responsible for vesicle formation, movement, tethering and fusion. RAB5A is required for the fusion of plasma membranes and early endosomes. Contributes to the regulation of filopodia extension. Required for the exosomal release of SDCBP, CD63, PDCD6IP and syndecan. Regulates maturation of apoptotic cell-containing phagosomes, probably downstream of DYN2 and PIK3C3.
KEGG Pathway
Ras sig.ling pathway (hsa04014 )
Mitophagy - animal (hsa04137 )
Endocytosis (hsa04144 )
Phagosome (hsa04145 )
Efferocytosis (hsa04148 )
Vasopressin-regulated water reabsorption (hsa04962 )
Amyotrophic lateral sclerosis (hsa05014 )
Pathways of neurodegeneration - multiple diseases (hsa05022 )
Salmonella infection (hsa05132 )
Amoebiasis (hsa05146 )
Tuberculosis (hsa05152 )
Reactome Pathway
TBC/RABGAPs (R-HSA-8854214 )
Clathrin-mediated endocytosis (R-HSA-8856828 )
RAB geranylgeranylation (R-HSA-8873719 )
RAB GEFs exchange GTP for GDP on RABs (R-HSA-8876198 )
Prevention of phagosomal-lysosomal fusion (R-HSA-9636383 )
Factors involved in megakaryocyte development and platelet production (R-HSA-983231 )
Synthesis of PIPs at the plasma membrane (R-HSA-1660499 )

Molecular Interaction Atlas (MIA) of This DOT

42 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Brucellosis DISEAYGH Definitive Genetic Variation [1]
Advanced cancer DISAT1Z9 Strong Biomarker [2]
Breast cancer DIS7DPX1 Strong Biomarker [3]
Breast carcinoma DIS2UE88 Strong Biomarker [3]
Breast neoplasm DISNGJLM Strong Altered Expression [3]
Bronchitis DISBM6EQ Strong Posttranslational Modification [4]
Cervical cancer DISFSHPF Strong Biomarker [5]
Cervical carcinoma DIST4S00 Strong Biomarker [5]
Cervical Intraepithelial neoplasia DISXP757 Strong Biomarker [5]
Colorectal carcinoma DIS5PYL0 Strong Biomarker [6]
Glioma DIS5RPEH Strong Altered Expression [7]
Hepatitis B virus infection DISLQ2XY Strong Altered Expression [8]
Hepatitis C virus infection DISQ0M8R Strong Biomarker [9]
Hepatocellular carcinoma DIS0J828 Strong Biomarker [10]
Influenza DIS3PNU3 Strong Altered Expression [11]
Lyme disease DISO70G5 Strong Biomarker [12]
Matthew-Wood syndrome DISA7HR7 Strong Biomarker [13]
Metastatic malignant neoplasm DIS86UK6 Strong Altered Expression [14]
Motor neurone disease DISUHWUI Strong Biomarker [15]
Myocardial ischemia DISFTVXF Strong Biomarker [16]
Nephrotic syndrome DISSPSC2 Strong Genetic Variation [17]
Non-alcoholic steatohepatitis DIST4788 Strong Altered Expression [18]
Oculocerebrorenal syndrome DIS8TEDY Strong Biomarker [19]
Renal cell carcinoma DISQZ2X8 Strong Altered Expression [20]
Triple negative breast cancer DISAMG6N Strong Biomarker [21]
Amyotrophic lateral sclerosis DISF7HVM moderate Altered Expression [22]
Rabies DISSC4V5 Disputed Biomarker [23]
Alzheimer disease DISF8S70 Limited Biomarker [24]
Asthma DISW9QNS Limited Biomarker [25]
Epithelial ovarian cancer DIS56MH2 Limited Altered Expression [26]
Lung adenocarcinoma DISD51WR Limited Altered Expression [27]
Lung cancer DISCM4YA Limited Altered Expression [27]
Lung carcinoma DISTR26C Limited Altered Expression [27]
Melanoma DIS1RRCY Limited Biomarker [28]
Neoplasm DISZKGEW Limited Altered Expression [6]
Nervous system inflammation DISB3X5A Limited Altered Expression [29]
Non-small-cell lung cancer DIS5Y6R9 Limited Altered Expression [27]
Ovarian cancer DISZJHAP Limited Altered Expression [26]
Ovarian neoplasm DISEAFTY Limited Altered Expression [26]
Pancreatic cancer DISJC981 Limited Biomarker [30]
Prostate cancer DISF190Y Limited Biomarker [31]
Prostate carcinoma DISMJPLE Limited Biomarker [31]
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⏷ Show the Full List of 42 Disease(s)
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 decreases the methylation of Ras-related protein Rab-5A (RAB5A). [32]
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene affects the methylation of Ras-related protein Rab-5A (RAB5A). [42]
PMID28870136-Compound-52 DMFDERP Patented PMID28870136-Compound-52 increases the phosphorylation of Ras-related protein Rab-5A (RAB5A). [43]
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13 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-related protein Rab-5A (RAB5A). [33]
Tretinoin DM49DUI Approved Tretinoin decreases the expression of Ras-related protein Rab-5A (RAB5A). [34]
Ivermectin DMDBX5F Approved Ivermectin decreases the expression of Ras-related protein Rab-5A (RAB5A). [35]
Arsenic trioxide DM61TA4 Approved Arsenic trioxide increases the expression of Ras-related protein Rab-5A (RAB5A). [36]
Marinol DM70IK5 Approved Marinol increases the expression of Ras-related protein Rab-5A (RAB5A). [37]
Phenobarbital DMXZOCG Approved Phenobarbital affects the expression of Ras-related protein Rab-5A (RAB5A). [38]
Bortezomib DMNO38U Approved Bortezomib decreases the expression of Ras-related protein Rab-5A (RAB5A). [39]
Urethane DM7NSI0 Phase 4 Urethane increases the expression of Ras-related protein Rab-5A (RAB5A). [40]
Dihydrotestosterone DM3S8XC Phase 4 Dihydrotestosterone increases the expression of Ras-related protein Rab-5A (RAB5A). [41]
Tamibarotene DM3G74J Phase 3 Tamibarotene affects the expression of Ras-related protein Rab-5A (RAB5A). [34]
Bisphenol A DM2ZLD7 Investigative Bisphenol A increases the expression of Ras-related protein Rab-5A (RAB5A). [44]
Trichostatin A DM9C8NX Investigative Trichostatin A increases the expression of Ras-related protein Rab-5A (RAB5A). [45]
Taurine DMVW7N3 Investigative Taurine decreases the expression of Ras-related protein Rab-5A (RAB5A). [46]
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⏷ Show the Full List of 13 Drug(s)

References

1 Association of an IRF3 putative functional uORF variant with resistance to Brucella infection: A candidate gene based analysis of InDel polymorphisms in goats.Cytokine. 2019 Mar;115:109-115. doi: 10.1016/j.cyto.2018.11.024. Epub 2018 Nov 23.
2 Disruption of Endolysosomal RAB5/7 Efficiently Eliminates Colorectal Cancer Stem Cells.Cancer Res. 2019 Apr 1;79(7):1426-1437. doi: 10.1158/0008-5472.CAN-18-2192. Epub 2019 Feb 14.
3 The Protease Activated Receptor2 Promotes Rab5a Mediated Generation of Pro-metastatic Microvesicles.Sci Rep. 2018 May 9;8(1):7357. doi: 10.1038/s41598-018-25725-w.
4 Infectious bronchitis virus entry mainly depends on clathrin mediated endocytosis and requires classical endosomal/lysosomal system.Virology. 2019 Feb;528:118-136. doi: 10.1016/j.virol.2018.12.012. Epub 2018 Dec 28.
5 Expression levels and roles of EMC-6, Beclin1, and Rab5a in the cervical cancer.Eur Rev Med Pharmacol Sci. 2017 Jul;21(13):3038-3046.
6 Increased expression of Rab5A predicts metastasis and poor prognosis in colorectal cancer patients.Int J Clin Exp Pathol. 2015 Jun 1;8(6):6974-80. eCollection 2015.
7 Malat1 activates autophagy and promotes cell proliferation by sponging miR-101 and upregulating STMN1, RAB5A and ATG4D expression in glioma.Biochem Biophys Res Commun. 2017 Oct 21;492(3):480-486. doi: 10.1016/j.bbrc.2017.08.070. Epub 2017 Aug 20.
8 Regulation of hepatitis B virus infection by Rab5, Rab7, and the endolysosomal compartment.J Virol. 2013 Jun;87(11):6415-27. doi: 10.1128/JVI.00393-13. Epub 2013 Mar 27.
9 Rab5 Enhances Classical Swine Fever Virus Proliferation and Interacts with Viral NS4B Protein to Facilitate Formation of NS4B Related Complex.Front Microbiol. 2017 Aug 8;8:1468. doi: 10.3389/fmicb.2017.01468. eCollection 2017.
10 Overexpression of Rab5a promotes hepatocellular carcinoma cell proliferation and invasion via FAK signaling pathway.Tumour Biol. 2016 Mar;37(3):3341-7. doi: 10.1007/s13277-015-4124-5. Epub 2015 Oct 6.
11 Differential requirements of Rab5 and Rab7 for endocytosis of influenza and other enveloped viruses.Traffic. 2003 May;4(5):333-43. doi: 10.1034/j.1600-0854.2003.00090.x.
12 ER-Coordinated Activities of Rab22a and Rab5a Drive Phagosomal Compaction and Intracellular Processing of Borrelia burgdorferi by Macrophages.Cell Rep. 2015 Sep 22;12(11):1816-30. doi: 10.1016/j.celrep.2015.08.027. Epub 2015 Sep 3.
13 SNHG14 enhances gemcitabine resistance by sponging miR-101 to stimulate cell autophagy in pancreatic cancer.Biochem Biophys Res Commun. 2019 Mar 19;510(4):508-514. doi: 10.1016/j.bbrc.2019.01.109. Epub 2019 Feb 5.
14 RABEX-5 plays an oncogenic role in breast cancer by activating MMP-9 pathway.J Exp Clin Cancer Res. 2013 Aug 13;32(1):52. doi: 10.1186/1756-9966-32-52.
15 Increased neuronal Rab5 immunoreactive endosomes do not colocalize with TDP-43 in motor neuron disease.Exp Neurol. 2010 Sep;225(1):133-9. doi: 10.1016/j.expneurol.2010.06.004. Epub 2010 Jun 15.
16 Cardioplegia prevents ischemia-induced transcriptional alterations of cytoprotective genes in rat hearts: a DNA microarray study.J Thorac Cardiovasc Surg. 2005 Oct;130(4):1151. doi: 10.1016/j.jtcvs.2005.06.027.
17 GAPVD1 and ANKFY1 Mutations Implicate RAB5 Regulation in Nephrotic Syndrome. J Am Soc Nephrol. 2018 Aug;29(8):2123-2138. doi: 10.1681/ASN.2017121312. Epub 2018 Jun 29.
18 Genomics of human fatty liver disease reveal mechanistically linked lipid droplet-associated gene regulations in bland steatosis and nonalcoholic steatohepatitis.Transl Res. 2016 Nov;177:41-69. doi: 10.1016/j.trsl.2016.06.003. Epub 2016 Jun 16.
19 Two closely related endocytic proteins that share a common OCRL-binding motif with APPL1.Proc Natl Acad Sci U S A. 2010 Feb 23;107(8):3511-6. doi: 10.1073/pnas.0914658107. Epub 2010 Feb 2.
20 The tumor susceptibility gene TMEM127 is mutated in renal cell carcinomas and modulates endolysosomal function.Hum Mol Genet. 2014 May 1;23(9):2428-39. doi: 10.1093/hmg/ddt638. Epub 2013 Dec 13.
21 TUFT1 promotes metastasis and chemoresistance in triple negative breast cancer through the TUFT1/Rab5/Rac1 pathway.Cancer Cell Int. 2019 Sep 23;19:242. doi: 10.1186/s12935-019-0961-4. eCollection 2019.
22 Rab5 and Alsin regulate stress-activated cytoprotective signaling on mitochondria.Elife. 2018 Feb 22;7:e32282. doi: 10.7554/eLife.32282.
23 Rabies virus co-localizes with early (Rab5) and late (Rab7) endosomal proteins in neuronal and SH-SY5Y cells.Virol Sin. 2017 Jun;32(3):207-215. doi: 10.1007/s12250-017-3968-9. Epub 2017 Jun 16.
24 Dysregulation of Rab5-mediated endocytic pathways in Alzheimer's disease.Traffic. 2018 Apr;19(4):253-262. doi: 10.1111/tra.12547. Epub 2018 Feb 5.
25 Establishment of extracellular signal-regulated kinase 1/2 bistability and sustained activation through Sprouty 2 and its relevance for epithelial function.Mol Cell Biol. 2010 Apr;30(7):1783-99. doi: 10.1128/MCB.01003-09. Epub 2010 Feb 1.
26 Rab5a overexpression promoting ovarian cancer cell proliferation may be associated with APPL1-related epidermal growth factor signaling pathway.Cancer Sci. 2010 Jun;101(6):1454-62. doi: 10.1111/j.1349-7006.2010.01558.x. Epub 2010 Mar 10.
27 Differential expression of RAB5A in human lung adenocarcinoma cells with different metastasis potential.Clin Exp Metastasis. 1999 May;17(3):213-9. doi: 10.1023/a:1006617016451.
28 AT2 Receptor Mediated Activation of the Tyrosine Phosphatase PTP1B Blocks Caveolin-1 Enhanced Migration, Invasion and Metastasis of Cancer Cells.Cancers (Basel). 2019 Sep 3;11(9):1299. doi: 10.3390/cancers11091299.
29 Ulk1 Governs Nerve Growth Factor/TrkA Signaling by Mediating Rab5 GTPase Activation in Porcine Hemagglutinating Encephalomyelitis Virus-Induced Neurodegenerative Disorders.J Virol. 2018 Jul 31;92(16):e00325-18. doi: 10.1128/JVI.00325-18. Print 2018 Aug 15.
30 Expression of Rab5a correlates with tumor progression in pancreatic carcinoma.Virchows Arch. 2017 May;470(5):527-536. doi: 10.1007/s00428-017-2098-y. Epub 2017 Feb 27.
31 Intracellular oxygen determined by respiration regulates localization of Ras and prenylated proteins.Cell Death Dis. 2015 Jul 16;6(7):e1825. doi: 10.1038/cddis.2015.64.
32 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.
33 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.
34 Differential modulation of PI3-kinase/Akt pathway during all-trans retinoic acid- and Am80-induced HL-60 cell differentiation revealed by DNA microarray analysis. Biochem Pharmacol. 2004 Dec 1;68(11):2177-86.
35 Quantitative proteomics reveals a broad-spectrum antiviral property of ivermectin, benefiting for COVID-19 treatment. J Cell Physiol. 2021 Apr;236(4):2959-2975. doi: 10.1002/jcp.30055. Epub 2020 Sep 22.
36 Essential role of cell cycle regulatory genes p21 and p27 expression in inhibition of breast cancer cells by arsenic trioxide. Med Oncol. 2011 Dec;28(4):1225-54.
37 JunD is involved in the antiproliferative effect of Delta9-tetrahydrocannabinol on human breast cancer cells. Oncogene. 2008 Aug 28;27(37):5033-44.
38 Reproducible chemical-induced changes in gene expression profiles in human hepatoma HepaRG cells under various experimental conditions. Toxicol In Vitro. 2009 Apr;23(3):466-75. doi: 10.1016/j.tiv.2008.12.018. Epub 2008 Dec 30.
39 The proapoptotic effect of zoledronic acid is independent of either the bone microenvironment or the intrinsic resistance to bortezomib of myeloma cells and is enhanced by the combination with arsenic trioxide. Exp Hematol. 2011 Jan;39(1):55-65.
40 Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
41 LSD1 activates a lethal prostate cancer gene network independently of its demethylase function. Proc Natl Acad Sci U S A. 2018 May 1;115(18):E4179-E4188.
42 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.
43 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.
44 Alternatives for the worse: Molecular insights into adverse effects of bisphenol a and substitutes during human adipocyte differentiation. Environ Int. 2021 Nov;156:106730. doi: 10.1016/j.envint.2021.106730. Epub 2021 Jun 27.
45 From transient transcriptome responses to disturbed neurodevelopment: role of histone acetylation and methylation as epigenetic switch between reversible and irreversible drug effects. Arch Toxicol. 2014 Jul;88(7):1451-68.
46 Taurine-responsive genes related to signal transduction as identified by cDNA microarray analyses of HepG2 cells. J Med Food. 2006 Spring;9(1):33-41. doi: 10.1089/jmf.2006.9.33.