Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTPF9D0K)

DOT Name Ras-related protein Rab-27B (RAB27B)
Synonyms EC 3.6.5.2; C25KG
Gene Name RAB27B
Related Disease
Acute myelogenous leukaemia ( )
Advanced cancer ( )
Alzheimer disease ( )
Astrocytoma ( )
Bladder cancer ( )
Breast cancer ( )
Breast carcinoma ( )
Breast neoplasm ( )
Glioblastoma multiforme ( )
Glioma ( )
Gout ( )
Griscelli syndrome ( )
Hepatocellular carcinoma ( )
Hypopigmentation of the skin ( )
Kidney cancer ( )
Kidney neoplasm ( )
Lung adenocarcinoma ( )
Major depressive disorder ( )
Malignant glioma ( )
Mood disorder ( )
Neoplasm ( )
Non-small-cell lung cancer ( )
Pancreatic tumour ( )
Platelet storage pool deficiency ( )
Rectal adenocarcinoma ( )
Renal carcinoma ( )
Squamous cell carcinoma ( )
Urinary bladder cancer ( )
Urinary bladder neoplasm ( )
Gastrointestinal stromal tumour ( )
Estrogen-receptor positive breast cancer ( )
Bone osteosarcoma ( )
Choroideremia ( )
Clear cell renal carcinoma ( )
Colorectal carcinoma ( )
Malignant tumor of nasopharynx ( )
Metastatic malignant neoplasm ( )
Nasopharyngeal carcinoma ( )
Osteosarcoma ( )
Pancreatic cancer ( )
Pancreatic ductal carcinoma ( )
Prostate cancer ( )
Prostate carcinoma ( )
UniProt ID
RB27B_HUMAN
3D Structure
Download
2D Sequence (FASTA)
Download
3D Structure (PDB)
Download
PDB ID
2F7S
EC Number
3.6.5.2
Pfam ID
PF00071
Sequence
MTDGDYDYLIKLLALGDSGVGKTTFLYRYTDNKFNPKFITTVGIDFREKRVVYNAQGPNG
SSGKAFKVHLQLWDTAGQERFRSLTTAFFRDAMGFLLMFDLTSQQSFLNVRNWMSQLQAN
AYCENPDIVLIGNKADLPDQREVNERQARELADKYGIPYFETSAATGQNVEKAVETLLDL
IMKRMEQCVEKTQIPDTVNGGNSGNLDGEKPPEKKCIC
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 homeostasis of late endocytic pathway, including endosomal positioning, maturation and secretion. Plays a role in NTRK2/TRKB axonal anterograde transport by facilitating the association of NTRK2/TRKB with KLC1. May be involved in targeting uroplakins to urothelial apical membranes.
Tissue Specificity Expressed primarily in testis.
KEGG Pathway
Pancreatic secretion (hsa04972 )
Reactome Pathway
RAB geranylgeranylation (R-HSA-8873719 )
RAB GEFs exchange GTP for GDP on RABs (R-HSA-8876198 )
Platelet degranulation (R-HSA-114608 )

Molecular Interaction Atlas (MIA) of This DOT

43 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Acute myelogenous leukaemia DISCSPTN Strong Biomarker [1]
Advanced cancer DISAT1Z9 Strong Altered Expression [2]
Alzheimer disease DISF8S70 Strong Biomarker [3]
Astrocytoma DISL3V18 Strong Biomarker [4]
Bladder cancer DISUHNM0 Strong Altered Expression [5]
Breast cancer DIS7DPX1 Strong Altered Expression [6]
Breast carcinoma DIS2UE88 Strong Altered Expression [6]
Breast neoplasm DISNGJLM Strong Altered Expression [6]
Glioblastoma multiforme DISK8246 Strong Biomarker [4]
Glioma DIS5RPEH Strong Biomarker [7]
Gout DISHC0U7 Strong Genetic Variation [8]
Griscelli syndrome DISTHCOQ Strong Biomarker [9]
Hepatocellular carcinoma DIS0J828 Strong Biomarker [10]
Hypopigmentation of the skin DIS39YKC Strong Altered Expression [11]
Kidney cancer DISBIPKM Strong Altered Expression [12]
Kidney neoplasm DISBNZTN Strong Biomarker [12]
Lung adenocarcinoma DISD51WR Strong Biomarker [13]
Major depressive disorder DIS4CL3X Strong Genetic Variation [14]
Malignant glioma DISFXKOV Strong Altered Expression [4]
Mood disorder DISLVMWO Strong Genetic Variation [15]
Neoplasm DISZKGEW Strong Biomarker [2]
Non-small-cell lung cancer DIS5Y6R9 Strong Altered Expression [16]
Pancreatic tumour DIS3U0LK Strong Altered Expression [17]
Platelet storage pool deficiency DISHODOH Strong Biomarker [18]
Rectal adenocarcinoma DIS8R9VO Strong Altered Expression [19]
Renal carcinoma DISER9XT Strong Altered Expression [12]
Squamous cell carcinoma DISQVIFL Strong Altered Expression [16]
Urinary bladder cancer DISDV4T7 Strong Altered Expression [5]
Urinary bladder neoplasm DIS7HACE Strong Altered Expression [5]
Gastrointestinal stromal tumour DIS6TJYS moderate Altered Expression [20]
Estrogen-receptor positive breast cancer DIS1H502 Disputed Biomarker [21]
Bone osteosarcoma DIST1004 Limited Biomarker [22]
Choroideremia DISH4N9B Limited Biomarker [23]
Clear cell renal carcinoma DISBXRFJ Limited Altered Expression [24]
Colorectal carcinoma DIS5PYL0 Limited Biomarker [2]
Malignant tumor of nasopharynx DISTGIGF Limited Biomarker [25]
Metastatic malignant neoplasm DIS86UK6 Limited Biomarker [26]
Nasopharyngeal carcinoma DISAOTQ0 Limited Biomarker [25]
Osteosarcoma DISLQ7E2 Limited Biomarker [22]
Pancreatic cancer DISJC981 Limited Biomarker [27]
Pancreatic ductal carcinoma DIS26F9Q Limited Altered Expression [27]
Prostate cancer DISF190Y Limited Altered Expression [26]
Prostate carcinoma DISMJPLE Limited Altered Expression [26]
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⏷ Show the Full List of 43 Disease(s)
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
This DOT Affected the Drug Response of 2 Drug(s)
Drug Name Drug ID Highest Status Interaction REF
Temozolomide DMKECZD Approved Ras-related protein Rab-27B (RAB27B) affects the response to substance of Temozolomide. [40]
DTI-015 DMXZRW0 Approved Ras-related protein Rab-27B (RAB27B) affects the response to substance of DTI-015. [40]
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2 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-27B (RAB27B). [28]
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene increases the methylation of Ras-related protein Rab-27B (RAB27B). [35]
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10 Drug(s) Affected the Gene/Protein Processing of This DOT
Drug Name Drug ID Highest Status Interaction REF
Doxorubicin DMVP5YE Approved Doxorubicin decreases the expression of Ras-related protein Rab-27B (RAB27B). [29]
Estradiol DMUNTE3 Approved Estradiol decreases the expression of Ras-related protein Rab-27B (RAB27B). [30]
Arsenic trioxide DM61TA4 Approved Arsenic trioxide decreases the expression of Ras-related protein Rab-27B (RAB27B). [31]
Testosterone DM7HUNW Approved Testosterone decreases the expression of Ras-related protein Rab-27B (RAB27B). [32]
Progesterone DMUY35B Approved Progesterone increases the expression of Ras-related protein Rab-27B (RAB27B). [33]
Troglitazone DM3VFPD Approved Troglitazone decreases the expression of Ras-related protein Rab-27B (RAB27B). [34]
Bisphenol A DM2ZLD7 Investigative Bisphenol A increases the expression of Ras-related protein Rab-27B (RAB27B). [36]
Trichostatin A DM9C8NX Investigative Trichostatin A increases the expression of Ras-related protein Rab-27B (RAB27B). [37]
Formaldehyde DM7Q6M0 Investigative Formaldehyde decreases the expression of Ras-related protein Rab-27B (RAB27B). [38]
chloropicrin DMSGBQA Investigative chloropicrin increases the expression of Ras-related protein Rab-27B (RAB27B). [39]
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⏷ Show the Full List of 10 Drug(s)

References

1 miR-34c-5p promotes eradication of acute myeloid leukemia stem cells by inducing senescence through selective RAB27B targeting to inhibit exosome shedding.Leukemia. 2018 May;32(5):1180-1188. doi: 10.1038/s41375-018-0015-2. Epub 2018 Feb 2.
2 RAB27B-activated secretion of stem-like tumor exosomes delivers the biomarker microRNA-146a-5p, which promotes tumorigenesis and associates with an immunosuppressive tumor microenvironment in colorectal cancer.Int J Cancer. 2019 Oct 15;145(8):2209-2224. doi: 10.1002/ijc.32338. Epub 2019 Apr 30.
3 Targeted Quantitative Proteomic Approach for High-Throughput Quantitative Profiling of Small GTPases in Brain Tissues of Alzheimer's Disease Patients.Anal Chem. 2019 Oct 1;91(19):12307-12314. doi: 10.1021/acs.analchem.9b02485. Epub 2019 Sep 10.
4 Hypomethylated Rab27b is a progression-associated prognostic biomarker of glioma regulating MMP-9 to promote invasion.Oncol Rep. 2015 Sep;34(3):1503-9. doi: 10.3892/or.2015.4125. Epub 2015 Jul 13.
5 Cellular disposal of miR23b by RAB27-dependent exosome release is linked to acquisition of metastatic properties.Cancer Res. 2014 Oct 15;74(20):5758-71. doi: 10.1158/0008-5472.CAN-13-3512. Epub 2014 Sep 26.
6 Inactivation of Rab27B-dependent signaling pathway by calycosin inhibits migration and invasion of ER-negative breast cancer cells.Gene. 2019 Aug 15;709:48-55. doi: 10.1016/j.gene.2019.04.005. Epub 2019 Apr 16.
7 MicroRNA-599 suppresses glioma progression by targeting RAB27B.Oncol Lett. 2018 Jul;16(1):1243-1252. doi: 10.3892/ol.2018.8727. Epub 2018 May 16.
8 Genome-wide association study identifies ABCG2 (BCRP) as an allopurinol transporter and a determinant of drug response. Clin Pharmacol Ther. 2015 May;97(5):518-25.
9 Functional redundancy of Rab27 proteins and the pathogenesis of Griscelli syndrome.J Clin Invest. 2002 Jul;110(2):247-57. doi: 10.1172/JCI15058.
10 Downregulation of serum RAB27B confers improved prognosis and is associated with hepatocellular carcinoma progression through PI3K-AKT-P21 signaling.Oncotarget. 2017 May 19;8(37):61118-61132. doi: 10.18632/oncotarget.18010. eCollection 2017 Sep 22.
11 Molecular cloning and characterization of rab27a and rab27b, novel human rab proteins shared by melanocytes and platelets.Biochem Mol Med. 1997 Feb;60(1):27-37. doi: 10.1006/bmme.1996.2559.
12 Gene expression and protein array studies of folliculin-regulated pathways.Anticancer Res. 2012 Nov;32(11):4663-70.
13 Rab27b Is a Potential Indicator for Lymph Node Metastasis and Unfavorable Prognosis in Lung Adenocarcinoma.Dis Markers. 2018 Dec 2;2018:7293962. doi: 10.1155/2018/7293962. eCollection 2018.
14 Genome-wide meta-analysis of depression identifies 102 independent variants and highlights the importance of the prefrontal brain regions.Nat Neurosci. 2019 Mar;22(3):343-352. doi: 10.1038/s41593-018-0326-7. Epub 2019 Feb 4.
15 Meta-analysis of genome-wide association studies for neuroticism in 449,484 individuals identifies novel genetic loci and pathways.Nat Genet. 2018 Jul;50(7):920-927. doi: 10.1038/s41588-018-0151-7. Epub 2018 Jun 25.
16 Prognostic role of Rab27A and Rab27B expression in patients with non-small cell lung carcinoma.Thorac Cancer. 2019 Feb;10(2):143-149. doi: 10.1111/1759-7714.12919. Epub 2018 Nov 27.
17 ZIP4 Promotes Muscle Wasting and Cachexia in Mice With Orthotopic Pancreatic Tumors by Stimulating RAB27B-Regulated Release of Extracellular Vesicles From Cancer Cells.Gastroenterology. 2019 Feb;156(3):722-734.e6. doi: 10.1053/j.gastro.2018.10.026. Epub 2018 Oct 17.
18 Rab27b regulates number and secretion of platelet dense granules.Proc Natl Acad Sci U S A. 2007 Apr 3;104(14):5872-7. doi: 10.1073/pnas.0609879104. Epub 2007 Mar 23.
19 Identification of the potential biomarkers for the metastasis of rectal adenocarcinoma.APMIS. 2017 Feb;125(2):93-100. doi: 10.1111/apm.12633. Epub 2016 Dec 28.
20 Prognostic value of Rab27B nuclear expression in gastrointestinal stromal tumors.Dis Markers. 2014;2014:942181. doi: 10.1155/2014/942181. Epub 2014 Oct 14.
21 The secretory small GTPase Rab27B as a marker for breast cancer progression.Oncotarget. 2010 Aug;1(4):304-308. doi: 10.18632/oncotarget.140.
22 MiR-193a-3p and miR-193a-5p suppress the metastasis of human osteosarcoma cells by down-regulating Rab27B and SRR, respectively. Clin Exp Metastasis. 2016 Apr;33(4):359-72.
23 Rab GTPase prenylation hierarchy and its potential role in choroideremia disease.PLoS One. 2013 Dec 16;8(12):e81758. doi: 10.1371/journal.pone.0081758. eCollection 2013.
24 RAB27A is an independent prognostic factor in clear cell renal cell carcinoma.Biomark Med. 2019 Mar;13(4):239-247. doi: 10.2217/bmm-2018-0336. Epub 2019 Jan 21.
25 MiR-20a-5p promotes radio-resistance by targeting Rab27B in nasopharyngeal cancer cells.Cancer Cell Int. 2017 Mar 1;17:32. doi: 10.1186/s12935-017-0389-7. eCollection 2017.
26 RAB27A, RAB27B and VPS36 are downregulated in advanced prostate cancer and show functional relevance in prostate cancer cells.Int J Oncol. 2017 Mar;50(3):920-932. doi: 10.3892/ijo.2017.3872. Epub 2017 Feb 10.
27 Effects of Rab27A and Rab27B on Invasion, Proliferation, Apoptosis, and Chemoresistance in Human Pancreatic Cancer Cells.Pancreas. 2017 Oct;46(9):1173-1179. doi: 10.1097/MPA.0000000000000910.
28 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.
29 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.
30 17-Estradiol Activates HSF1 via MAPK Signaling in ER-Positive Breast Cancer Cells. Cancers (Basel). 2019 Oct 11;11(10):1533. doi: 10.3390/cancers11101533.
31 Arsenic suppresses gene expression in promyelocytic leukemia cells partly through Sp1 oxidation. Blood. 2005 Jul 1;106(1):304-10.
32 The exosome-like vesicles derived from androgen exposed-prostate stromal cells promote epithelial cells proliferation and epithelial-mesenchymal transition. Toxicol Appl Pharmacol. 2021 Jan 15;411:115384. doi: 10.1016/j.taap.2020.115384. Epub 2020 Dec 25.
33 Effects of progesterone treatment on expression of genes involved in uterine quiescence. Reprod Sci. 2011 Aug;18(8):781-97.
34 Adipogenic Effects and Gene Expression Profiling of Firemaster? 550 Components in Human Primary Preadipocytes. Environ Health Perspect. 2017 Sep 14;125(9):097013. doi: 10.1289/EHP1318.
35 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.
36 Bisphenol A induces DSB-ATM-p53 signaling leading to cell cycle arrest, senescence, autophagy, stress response, and estrogen release in human fetal lung fibroblasts. Arch Toxicol. 2018 Apr;92(4):1453-1469.
37 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.
38 Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
39 Molecular targets of chloropicrin in human airway epithelial cells. Toxicol In Vitro. 2017 Aug;42:247-254.
40 Tumor necrosis factor-alpha-induced protein 3 as a putative regulator of nuclear factor-kappaB-mediated resistance to O6-alkylating agents in human glioblastomas. J Clin Oncol. 2006 Jan 10;24(2):274-87. doi: 10.1200/JCO.2005.02.9405. Epub 2005 Dec 19.