Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT60A0E9)

DOT Name Ras-related protein Rab-7b (RAB7B)
Gene Name RAB7B
Related Disease
Huntington disease ( )
Malaria ( )
Nervous system disease ( )
Adult lymphoma ( )
Alzheimer disease ( )
Cerebral infarction ( )
Charcot marie tooth disease ( )
Charcot-Marie-Tooth disease type 2B ( )
Cholangiocarcinoma ( )
Congenital contractural arachnodactyly ( )
Hepatitis B virus infection ( )
Hepatitis C virus infection ( )
Hereditary sensory and autonomic neuropathy ( )
Hereditary sensory and autonomic neuropathy type 1 ( )
Influenza ( )
Intervertebral disc degeneration ( )
Lymphoma ( )
Neoplasm ( )
Osteoporosis ( )
Parkinson disease ( )
Pediatric lymphoma ( )
Promyelocytic leukaemia ( )
Stroke ( )
Triple negative breast cancer ( )
Vici syndrome ( )
Advanced cancer ( )
Peripheral sensory neuropathies ( )
Chediak-Higashi syndrome ( )
Hemolytic-uremic syndrome ( )
Rabies ( )
Toxic shock syndrome ( )
Warburg micro syndrome 1 ( )
Acute coronary syndrome ( )
Choroideremia ( )
Cystinosis ( )
Lysosomal acid lipase deficiency ( )
Melanoma ( )
Neuroblastoma ( )
Wolman disease ( )
UniProt ID
RAB7B_HUMAN
3D Structure
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2D Sequence (FASTA)
Download
3D Structure (PDB)
Download
Pfam ID
PF00071
Sequence
MNPRKKVDLKLIIVGAIGVGKTSLLHQYVHKTFYEEYQTTLGASILSKIIILGDTTLKLQ
IWDTGGQERFRSMVSTFYKGSDGCILAFDVTDLESFEALDIWRGDVLAKIVPMEQSYPMV
LLGNKIDLADRKVPQEVAQGWCREKDIPYFEVSAKNDINVVQAFEMLASRALSRYQSILE
NHLTESIKLSPDQSRSRCC
Function
Controls vesicular trafficking from endosomes to the trans-Golgi network (TGN). Acts as a negative regulator of TLR9 signaling and can suppress TLR9-triggered TNFA, IL6, and IFNB production in macrophages by promoting TLR9 lysosomal degradation. Also negatively regulates TLR4 signaling in macrophages by promoting lysosomal degradation of TLR4. Promotes megakaryocytic differentiation by increasing NF-kappa-B-dependent IL6 production and subsequently enhancing the association of STAT3 with GATA1. Not involved in the regulation of the EGF- and EGFR degradation pathway.
Tissue Specificity Expressed in heart, placenta, lung, skeletal muscle and peripheral blood leukocyte.
KEGG Pathway
Mitophagy - animal (hsa04137 )
Autophagy - animal (hsa04140 )
Phagosome (hsa04145 )
Efferocytosis (hsa04148 )
Salmonella infection (hsa05132 )
Amoebiasis (hsa05146 )
Reactome Pathway
RAB geranylgeranylation (R-HSA-8873719 )
RAB GEFs exchange GTP for GDP on RABs (R-HSA-8876198 )
TBC/RABGAPs (R-HSA-8854214 )

Molecular Interaction Atlas (MIA) of This DOT

39 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Huntington disease DISQPLA4 Definitive Biomarker [1]
Malaria DISQ9Y50 Definitive Altered Expression [2]
Nervous system disease DISJ7GGT Definitive Biomarker [1]
Adult lymphoma DISK8IZR Strong Altered Expression [3]
Alzheimer disease DISF8S70 Strong Biomarker [4]
Cerebral infarction DISR1WNP Strong Altered Expression [5]
Charcot marie tooth disease DIS3BT2L Strong Genetic Variation [6]
Charcot-Marie-Tooth disease type 2B DIS00RWZ Strong Biomarker [6]
Cholangiocarcinoma DIS71F6X Strong Biomarker [7]
Congenital contractural arachnodactyly DISOM1K7 Strong Biomarker [7]
Hepatitis B virus infection DISLQ2XY Strong Altered Expression [8]
Hepatitis C virus infection DISQ0M8R Strong Biomarker [9]
Hereditary sensory and autonomic neuropathy DIS2VOAM Strong Genetic Variation [10]
Hereditary sensory and autonomic neuropathy type 1 DISLSPO4 Strong Biomarker [11]
Influenza DIS3PNU3 Strong Altered Expression [12]
Intervertebral disc degeneration DISG3AIM Strong Biomarker [13]
Lymphoma DISN6V4S Strong Altered Expression [3]
Neoplasm DISZKGEW Strong Altered Expression [14]
Osteoporosis DISF2JE0 Strong Biomarker [15]
Parkinson disease DISQVHKL Strong Biomarker [16]
Pediatric lymphoma DIS51BK2 Strong Altered Expression [3]
Promyelocytic leukaemia DISYGG13 Strong Biomarker [17]
Stroke DISX6UHX Strong Biomarker [5]
Triple negative breast cancer DISAMG6N Strong Biomarker [18]
Vici syndrome DISSUIIM Strong Biomarker [19]
Advanced cancer DISAT1Z9 moderate Biomarker [20]
Peripheral sensory neuropathies DISYWI6M moderate Genetic Variation [21]
Chediak-Higashi syndrome DISPJLLO Disputed Altered Expression [22]
Hemolytic-uremic syndrome DISSCBGW Disputed Biomarker [23]
Rabies DISSC4V5 Disputed Biomarker [24]
Toxic shock syndrome DISX5S53 Disputed Biomarker [25]
Warburg micro syndrome 1 DIS90EI2 Disputed Biomarker [6]
Acute coronary syndrome DIS7DYEW Limited Biomarker [26]
Choroideremia DISH4N9B Limited Biomarker [27]
Cystinosis DISXY3VI Limited Altered Expression [28]
Lysosomal acid lipase deficiency DISO6W4Z Limited Altered Expression [29]
Melanoma DIS1RRCY Limited Biomarker [30]
Neuroblastoma DISVZBI4 Limited Biomarker [31]
Wolman disease DIS8BKL5 Limited Altered Expression [29]
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⏷ Show the Full List of 39 Disease(s)
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
11 Drug(s) Affected the Gene/Protein Processing of This DOT
Drug Name Drug ID Highest Status Interaction REF
Valproate DMCFE9I Approved Valproate increases the expression of Ras-related protein Rab-7b (RAB7B). [32]
Temozolomide DMKECZD Approved Temozolomide decreases the expression of Ras-related protein Rab-7b (RAB7B). [33]
Vorinostat DMWMPD4 Approved Vorinostat increases the expression of Ras-related protein Rab-7b (RAB7B). [34]
Panobinostat DM58WKG Approved Panobinostat increases the expression of Ras-related protein Rab-7b (RAB7B). [34]
Niclosamide DMJAGXQ Approved Niclosamide increases the expression of Ras-related protein Rab-7b (RAB7B). [35]
Hydroquinone DM6AVR4 Approved Hydroquinone decreases the expression of Ras-related protein Rab-7b (RAB7B). [36]
Sodium lauryl sulfate DMLJ634 Approved Sodium lauryl sulfate decreases the expression of Ras-related protein Rab-7b (RAB7B). [37]
(+)-JQ1 DM1CZSJ Phase 1 (+)-JQ1 increases the expression of Ras-related protein Rab-7b (RAB7B). [38]
Bisphenol A DM2ZLD7 Investigative Bisphenol A increases the expression of Ras-related protein Rab-7b (RAB7B). [39]
Trichostatin A DM9C8NX Investigative Trichostatin A increases the expression of Ras-related protein Rab-7b (RAB7B). [40]
Acetaldehyde DMJFKG4 Investigative Acetaldehyde increases the expression of Ras-related protein Rab-7b (RAB7B). [41]
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⏷ Show the Full List of 11 Drug(s)

References

1 Rab7 may be a novel therapeutic target for neurologic diseases as a key regulator in autophagy.J Neurosci Res. 2017 Oct;95(10):1993-2004. doi: 10.1002/jnr.24034. Epub 2017 Feb 10.
2 Impaired placental autophagy in placental malaria.PLoS One. 2017 Nov 10;12(11):e0187291. doi: 10.1371/journal.pone.0187291. eCollection 2017.
3 EBV and KSHV Infection Dysregulates Autophagy to Optimize Viral Replication, Prevent Immune Recognition and Promote Tumorigenesis.Viruses. 2018 Oct 31;10(11):599. doi: 10.3390/v10110599.
4 Distinct Rab7-related Endosomal-Autophagic-Lysosomal Dysregulation Observed in Cortex and Hippocampus in APPswe/PSEN1dE9 Mouse Model of Alzheimer's Disease.Chin Med J (Engl). 2017 Dec 20;130(24):2941-2950. doi: 10.4103/0366-6999.220311.
5 Rab7b Overexpression-Ameliorated Ischemic Brain Damage Following tMCAO Involves Suppression of TLR4 and NF-B p65.J Mol Neurosci. 2019 Jun;68(2):163-170. doi: 10.1007/s12031-019-01295-y. Epub 2019 Mar 25.
6 Rab18 Collaborates with Rab7 to Modulate Lysosomal and Autophagy Activities in the Nervous System: an Overlapping Mechanism for Warburg Micro Syndrome and Charcot-Marie-Tooth Neuropathy Type 2B.Mol Neurobiol. 2019 Sep;56(9):6095-6105. doi: 10.1007/s12035-019-1471-z. Epub 2019 Feb 5.
7 Disruption of endocytic trafficking protein Rab7 impairs invasiveness of cholangiocarcinoma cells.Cancer Biomark. 2017 Sep 7;20(3):255-266. doi: 10.3233/CBM-170030.
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 Hepatitis C virus promotes virion secretion through cleavage of the Rab7 adaptor protein RILP.Proc Natl Acad Sci U S A. 2016 Nov 1;113(44):12484-12489. doi: 10.1073/pnas.1607277113. Epub 2016 Oct 17.
10 Genes for hereditary sensory and autonomic neuropathies: a genotype-phenotype correlation.Brain. 2009 Oct;132(Pt 10):2699-711. doi: 10.1093/brain/awp198. Epub 2009 Aug 3.
11 A novel RAB7 mutation associated with ulcero-mutilating neuropathy.Ann Neurol. 2004 Oct;56(4):586-90. doi: 10.1002/ana.20281.
12 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.
13 Rab7 delays intervertebral disc degeneration through the inhibition of the p38MAPK pathway.Biochem Biophys Res Commun. 2019 Jun 30;514(3):835-841. doi: 10.1016/j.bbrc.2019.04.184. Epub 2019 May 9.
14 Tumor-Derived Extracellular Vesicles Breach the Intact Blood-Brain Barrier via Transcytosis.ACS Nano. 2019 Dec 24;13(12):13853-13865. doi: 10.1021/acsnano.9b04397. Epub 2019 Sep 10.
15 Proteomic analysis of circulating monocytes in Chinese premenopausal females with extremely discordant bone mineral density.Proteomics. 2008 Oct;8(20):4259-72. doi: 10.1002/pmic.200700480.
16 FYCO1 mediates clearance of -synuclein aggregates through a Rab7-dependent mechanism.J Neurochem. 2018 Aug;146(4):474-492. doi: 10.1111/jnc.14461. Epub 2018 Jul 23.
17 Rab7b, a novel lysosome-associated small GTPase, is involved in monocytic differentiation of human acute promyelocytic leukemia cells.Biochem Biophys Res Commun. 2004 Jun 4;318(3):792-9. doi: 10.1016/j.bbrc.2004.04.115.
18 Phosphorylation of RAB7 by TBK1/IKK Regulates Innate Immune Signaling in Triple-Negative Breast Cancer.Cancer Res. 2020 Jan 1;80(1):44-56. doi: 10.1158/0008-5472.CAN-19-1310. Epub 2019 Oct 29.
19 The RBG-1-RBG-2 complex modulates autophagy activity by regulating lysosomal biogenesis and function in C. elegans.J Cell Sci. 2019 Oct 1;132(19):jcs234195. doi: 10.1242/jcs.234195.
20 RAB7 controls melanoma progression by exploiting a lineage-specific wiring of the endolysosomal pathway.Cancer Cell. 2014 Jul 14;26(1):61-76. doi: 10.1016/j.ccr.2014.04.030. Epub 2014 Jun 26.
21 SPTLC1 and RAB7 mutation analysis in dominantly inherited and idiopathic sensory neuropathies.J Neurol Neurosurg Psychiatry. 2005 Jul;76(7):1022-4. doi: 10.1136/jnnp.2004.050062.
22 Cloning and mapping of human Rab7 and Rab9 cDNA sequences and identification of a Rab9 pseudogene.Genomics. 1997 Apr 1;41(1):131-4. doi: 10.1006/geno.1997.4644.
23 Rab7b participation on the TLR4 (Toll-like receptor) endocytic pathway in Shiga toxin-associated Hemolytic Uremic Syndrome (HUS).Cytokine. 2019 Sep;121:154732. doi: 10.1016/j.cyto.2019.05.019. Epub 2019 May 30.
24 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.
25 Staphylococcus aureus Alpha-Toxin Induces the Formation of Dynamic Tubules Labeled with LC3 within Host Cells in a Rab7 and Rab1b-Dependent Manner.Front Cell Infect Microbiol. 2017 Oct 4;7:431. doi: 10.3389/fcimb.2017.00431. eCollection 2017.
26 Proteomic changes related to "bewildered" circulating platelets in the acute coronary syndrome.Proteomics. 2011 Aug;11(16):3335-48. doi: 10.1002/pmic.201000708. Epub 2011 Jul 14.
27 Structure of the Rab7:REP-1 complex: insights into the mechanism of Rab prenylation and choroideremia disease.Cell. 2004 Jun 11;117(6):749-60. doi: 10.1016/j.cell.2004.05.017.
28 Cystinosin, the small GTPase Rab11, and the Rab7 effector RILP regulate intracellular trafficking of the chaperone-mediated autophagy receptor LAMP2A.J Biol Chem. 2017 Jun 23;292(25):10328-10346. doi: 10.1074/jbc.M116.764076. Epub 2017 May 2.
29 Endothelial Rab7 GTPase mediates tumor growth and metastasis in lysosomal acid lipase-deficient mice.J Biol Chem. 2017 Nov 24;292(47):19198-19208. doi: 10.1074/jbc.M116.773093. Epub 2017 Sep 18.
30 N6-isopentenyladenosine dual targeting of AMPK and Rab7 prenylation inhibits melanoma growth through the impairment of autophagic flux.Cell Death Differ. 2018 Feb;25(2):353-367. doi: 10.1038/cdd.2017.165. Epub 2017 Oct 13.
31 Human Rab7 mutation mimics features of Charcot-Marie-Tooth neuropathy type 2B in Drosophila.Neurobiol Dis. 2014 May;65:211-9. doi: 10.1016/j.nbd.2014.01.021. Epub 2014 Feb 9.
32 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.
33 Temozolomide induces activation of Wnt/-catenin signaling in glioma cells via PI3K/Akt pathway: implications in glioma therapy. Cell Biol Toxicol. 2020 Jun;36(3):273-278. doi: 10.1007/s10565-019-09502-7. Epub 2019 Nov 22.
34 A transcriptome-based classifier to identify developmental toxicants by stem cell testing: design, validation and optimization for histone deacetylase inhibitors. Arch Toxicol. 2015 Sep;89(9):1599-618.
35 Mitochondrial Uncoupling Induces Epigenome Remodeling and Promotes Differentiation in Neuroblastoma. Cancer Res. 2023 Jan 18;83(2):181-194. doi: 10.1158/0008-5472.CAN-22-1029.
36 Keratinocyte-derived IL-36gama plays a role in hydroquinone-induced chemical leukoderma through inhibition of melanogenesis in human epidermal melanocytes. Arch Toxicol. 2019 Aug;93(8):2307-2320.
37 CXCL14 downregulation in human keratinocytes is a potential biomarker for a novel in vitro skin sensitization test. Toxicol Appl Pharmacol. 2020 Jan 1;386:114828. doi: 10.1016/j.taap.2019.114828. Epub 2019 Nov 14.
38 Targeting MYCN in neuroblastoma by BET bromodomain inhibition. Cancer Discov. 2013 Mar;3(3):308-23.
39 Bisphenol A and bisphenol S induce distinct transcriptional profiles in differentiating human primary preadipocytes. PLoS One. 2016 Sep 29;11(9):e0163318.
40 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.
41 Transcriptome profile analysis of saturated aliphatic aldehydes reveals carbon number-specific molecules involved in pulmonary toxicity. Chem Res Toxicol. 2014 Aug 18;27(8):1362-70.