General Information of Drug Off-Target (DOT) (ID: OT8ZN26V)

DOT Name Ras-related protein Rab-10 (RAB10)
Synonyms EC 3.6.5.2
Gene Name RAB10
Related Disease
Advanced cancer ( )
Alzheimer disease ( )
Bone osteosarcoma ( )
Esophageal squamous cell carcinoma ( )
Glioma ( )
Hepatocellular carcinoma ( )
Neoplasm ( )
Osteosarcoma ( )
Parkinson disease ( )
Acute myelogenous leukaemia ( )
Hyperglycemia ( )
Neuroblastoma ( )
UniProt ID
RAB10_HUMAN
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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PDB ID
5LPN; 5SZJ
EC Number
3.6.5.2
Pfam ID
PF00071
Sequence
MAKKTYDLLFKLLLIGDSGVGKTCVLFRFSDDAFNTTFISTIGIDFKIKTVELQGKKIKL
QIWDTAGQERFHTITTSYYRGAMGIMLVYDITNGKSFENISKWLRNIDEHANEDVERMLL
GNKCDMDDKRVVPKGKGEQIAREHGIRFFETSAKANINIEKAFLTLAEDILRKTPVKEPN
SENVDISSGGGVTGWKSKCC
Function
The small GTPases Rab are key regulators of intracellular membrane trafficking, from the formation of transport vesicles to their fusion with membranes. Rabs cycle between an inactive GDP-bound form and an active GTP-bound form that is able to recruit to membranes different set of downstream effectors directly responsible for vesicle formation, movement, tethering and fusion. That Rab is mainly involved in the biosynthetic transport of proteins from the Golgi to the plasma membrane. Regulates, for instance, SLC2A4/GLUT4 glucose transporter-enriched vesicles delivery to the plasma membrane. In parallel, it regulates the transport of TLR4, a toll-like receptor to the plasma membrane and therefore may be important for innate immune response. Also plays a specific role in asymmetric protein transport to the plasma membrane. In neurons, it is involved in axonogenesis through regulation of vesicular membrane trafficking toward the axonal plasma membrane. In epithelial cells, it regulates transport from the Golgi to the basolateral membrane. May play a role in the basolateral recycling pathway and in phagosome maturation. May play a role in endoplasmic reticulum dynamics and morphology controlling tubulation along microtubules and tubules fusion. Together with LRRK2, RAB8A, and RILPL1, it regulates ciliogenesis. When phosphorylated by LRRK2 on Thr-73, binds RILPL1 and inhibits ciliogenesis. Participates in the export of a subset of neosynthesized proteins through a Rab8-Rab10-Rab11-dependent endososomal export route ; (Microbial infection) Upon Legionella pneumophila infection promotes endoplasmic reticulum recruitment and bacterial replication. Plays a role in remodeling the Legionella-containing vacuole (LCV) into an endoplasmic reticulum-like vacuole.
Tissue Specificity Expressed in the hippocampus . Expressed in neutrophils (at protein level) . Expressed in the testis (at protein level) .
KEGG Pathway
Endocytosis (hsa04144 )
AMPK sig.ling pathway (hsa04152 )
Reactome Pathway
Neutrophil degranulation (R-HSA-6798695 )
RAB geranylgeranylation (R-HSA-8873719 )
RAB GEFs exchange GTP for GDP on RABs (R-HSA-8876198 )
Translocation of SLC2A4 (GLUT4) to the plasma membrane (R-HSA-1445148 )

Molecular Interaction Atlas (MIA) of This DOT

12 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Advanced cancer DISAT1Z9 Strong Genetic Variation [1]
Alzheimer disease DISF8S70 Strong Biomarker [2]
Bone osteosarcoma DIST1004 Strong Biomarker [3]
Esophageal squamous cell carcinoma DIS5N2GV Strong Biomarker [4]
Glioma DIS5RPEH Strong Biomarker [5]
Hepatocellular carcinoma DIS0J828 Strong Biomarker [6]
Neoplasm DISZKGEW Strong Biomarker [7]
Osteosarcoma DISLQ7E2 Strong Biomarker [3]
Parkinson disease DISQVHKL Strong Biomarker [8]
Acute myelogenous leukaemia DISCSPTN Limited Genetic Variation [9]
Hyperglycemia DIS0BZB5 Limited Biomarker [10]
Neuroblastoma DISVZBI4 Limited Biomarker [11]
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⏷ Show the Full List of 12 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 Ras-related protein Rab-10 (RAB10). [12]
Ciclosporin DMAZJFX Approved Ciclosporin increases the expression of Ras-related protein Rab-10 (RAB10). [13]
Acetaminophen DMUIE76 Approved Acetaminophen increases the expression of Ras-related protein Rab-10 (RAB10). [14]
Doxorubicin DMVP5YE Approved Doxorubicin decreases the expression of Ras-related protein Rab-10 (RAB10). [15]
Cupric Sulfate DMP0NFQ Approved Cupric Sulfate increases the expression of Ras-related protein Rab-10 (RAB10). [16]
Ivermectin DMDBX5F Approved Ivermectin decreases the expression of Ras-related protein Rab-10 (RAB10). [17]
Hydrogen peroxide DM1NG5W Approved Hydrogen peroxide affects the expression of Ras-related protein Rab-10 (RAB10). [18]
Zoledronate DMIXC7G Approved Zoledronate increases the expression of Ras-related protein Rab-10 (RAB10). [19]
Bisphenol A DM2ZLD7 Investigative Bisphenol A decreases the expression of Ras-related protein Rab-10 (RAB10). [21]
Sulforaphane DMQY3L0 Investigative Sulforaphane increases the expression of Ras-related protein Rab-10 (RAB10). [22]
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⏷ Show the Full List of 10 Drug(s)
1 Drug(s) Affected the Post-Translational Modifications of This DOT
Drug Name Drug ID Highest Status Interaction REF
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene affects the methylation of Ras-related protein Rab-10 (RAB10). [20]
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References

1 Silencing of Rab3D suppresses the proliferation and invasion of esophageal squamous cell carcinoma cells.Biomed Pharmacother. 2017 Jul;91:402-407. doi: 10.1016/j.biopha.2017.04.010. Epub 2017 May 2.
2 RAB10: an Alzheimer's disease resilience locus and potential drug target.Clin Interv Aging. 2018 Dec 28;14:73-79. doi: 10.2147/CIA.S159148. eCollection 2019.
3 MiR-329 suppresses osteosarcoma development by downregulating Rab10. FEBS Lett. 2016 Sep;590(17):2973-81.
4 Long Non-Coding RNA LINC00152 Regulates Cell Proliferation, Migration And Invasion In Esophageal Squamous Cell Carcinoma Via miR-107/Rab10 Axis.Onco Targets Ther. 2019 Oct 17;12:8553-8567. doi: 10.2147/OTT.S221515. eCollection 2019.
5 PSMB8-AS1 activated by ELK1 promotes cell proliferation in glioma via regulating miR-574-5p/RAB10.Biomed Pharmacother. 2020 Feb;122:109658. doi: 10.1016/j.biopha.2019.109658. Epub 2019 Dec 4.
6 RAB10 overexpression promotes tumor growth and indicates poor prognosis of hepatocellular carcinoma.Oncotarget. 2017 Apr 18;8(16):26434-26447. doi: 10.18632/oncotarget.15507.
7 miR?78a?p exerts tumor suppressive function on the tumorigenesis of esophageal squamous cell carcinoma by targeting Rab10.Int J Mol Med. 2018 Jul;42(1):381-391. doi: 10.3892/ijmm.2018.3639. Epub 2018 Apr 24.
8 Rab10 Phosphorylation is a Prominent Pathological Feature in Alzheimer's Disease.J Alzheimers Dis. 2018;63(1):157-165. doi: 10.3233/JAD-180023.
9 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.
10 [6]-Gingerol, from Zingiber officinale, potentiates GLP-1 mediated glucose-stimulated insulin secretion pathway in pancreatic -cells and increases RAB8/RAB10-regulated membrane presentation of GLUT4 transporters in skeletal muscle to improve hyperglycemia in Lepr(db/db) type 2 diabetic mice.BMC Complement Altern Med. 2017 Aug 9;17(1):395. doi: 10.1186/s12906-017-1903-0.
11 Linkage, whole genome sequence, and biological data implicate variants in RAB10 in Alzheimer's disease resilience.Genome Med. 2017 Nov 29;9(1):100. doi: 10.1186/s13073-017-0486-1.
12 Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
13 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.
14 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.
15 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.
16 Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
17 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.
18 Global gene expression analysis reveals differences in cellular responses to hydroxyl- and superoxide anion radical-induced oxidative stress in caco-2 cells. Toxicol Sci. 2010 Apr;114(2):193-203. doi: 10.1093/toxsci/kfp309. Epub 2009 Dec 31.
19 Zoledronate dysregulates fatty acid metabolism in renal tubular epithelial cells to induce nephrotoxicity. Arch Toxicol. 2018 Jan;92(1):469-485.
20 Effect of aflatoxin B(1), benzo[a]pyrene, and methapyrilene on transcriptomic and epigenetic alterations in human liver HepaRG cells. Food Chem Toxicol. 2018 Nov;121:214-223. doi: 10.1016/j.fct.2018.08.034. Epub 2018 Aug 26.
21 Environmental pollutant induced cellular injury is reflected in exosomes from placental explants. Placenta. 2020 Jan 1;89:42-49. doi: 10.1016/j.placenta.2019.10.008. Epub 2019 Oct 17.
22 Transcriptome and DNA methylation changes modulated by sulforaphane induce cell cycle arrest, apoptosis, DNA damage, and suppression of proliferation in human liver cancer cells. Food Chem Toxicol. 2020 Feb;136:111047. doi: 10.1016/j.fct.2019.111047. Epub 2019 Dec 12.