Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT2011SS)

DOT Name TBC1 domain family member 8 (TBC1D8)
Synonyms AD 3; Vascular Rab-GAP/TBC-containing protein
Gene Name TBC1D8
Related Disease
Alzheimer disease ( )
Alzheimer disease 3 ( )
Brain neoplasm ( )
Clear cell renal carcinoma ( )
Epithelial ovarian cancer ( )
Osteoporosis ( )
Ovarian cancer ( )
Ovarian neoplasm ( )
Renal cell carcinoma ( )
Neoplasm ( )
UniProt ID
TBCD8_HUMAN
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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Pfam ID
PF02893 ; PF00566
Sequence
MWLKPEEVLLKNALKLWVTQKSSCYFILQRRRGHGEGGGRLTGRLVGALDAVLDSNARVA
PFRILLQVPGSQVYSPIACGATLEEINQHWDWLEQNLLHTLSVFDNKDDIASFVKGKVKA
LIAEETSSRLAEQEEEPEKFREALVKFEARFNFPEAEKLVTYYSCCCWKGRVPRQGWLYL
SINHLCFYSFFLGKELKLVVPWVDIQKLERTSNVFLTDTIRITTQNKERDFSMFLNLDEV
FKVMEQLADVTLRRLLDNEVFDLDPDLQEPSQITKRDLEARAQNEFFRAFFRLPRKEKLH
AVVDCSLWTPFSRCHTTGRMFASDSYICFASREDGCCKIILPLREVVSIEKMEDTSLLPH
PIIVSIRSKVAFQFIELRDRDSLVEALLARLKQVHANHPVHYDTSADDDMASLVFHSTSM
CSDHRFGDLEMMSSQNSEESEKEKSPLMHPDALVTAFQQSGSQSPDSRMSREQIKISLWN
DHFVEYGRTVCMFRTEKIRKLVAMGIPESLRGRLWLLFSDAVTDLASHPGYYGNLVEESL
GKCCLVTEEIERDLHRSLPEHPAFQNETGIAALRRVLTAYAHRNPKIGYCQSMNILTSVL
LLYTKEEEAFWLLVAVCERMLPDYFNHRVIGAQVDQSVFEELIKGHLPELAEHMNDLSAL
ASVSLSWFLTLFLSIMPLESAVNVVDCFFYDGIKAIFQLGLAVLEANAEDLCSSKDDGQA
LMILSRFLDHIKNEDSPGPPVGSHHAFFSDDQEPYPVTDISDLIRDSYEKFGDQSVEQIE
HLRYKHRIRVLQGHEDTTKQNVLRVVIPEVSILPEDLEELYDLFKREHMMSCYWEQPRPM
ASRHDPSRPYAEQYRIDARQFAHLFQLVSPWTCGAHTEILAERTFRLLDDNMDQLIEFKA
FVSCLDIMYNGEMNEKIKLLYRLHIPPALTENDRDSQSPLRNPLLSTSRPLVFGKPNGDA
VDYQKQLKQMIKDLAKEKDKTEKELPKMSQREFIQFCKTLYSMFHEDPEENDLYQAIATV
TTLLLQIGEVGQRGSSSGSCSQECGEELRASAPSPEDSVFADTGKTPQDSQAFPEAAERD
WTVSLEHILASLLTEQSLVNFFEKPLDMKSKLENAKINQYNLKTFEMSHQSQSELKLSNL
Function May act as a GTPase-activating protein for Rab family protein(s).

Molecular Interaction Atlas (MIA) of This DOT

10 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Alzheimer disease DISF8S70 Strong Biomarker [1]
Alzheimer disease 3 DISVT69G Strong Biomarker [1]
Brain neoplasm DISY3EKS Strong Biomarker [2]
Clear cell renal carcinoma DISBXRFJ Strong Biomarker [1]
Epithelial ovarian cancer DIS56MH2 Strong Biomarker [3]
Osteoporosis DISF2JE0 Strong Genetic Variation [4]
Ovarian cancer DISZJHAP Strong Biomarker [3]
Ovarian neoplasm DISEAFTY Strong Biomarker [3]
Renal cell carcinoma DISQZ2X8 Strong Biomarker [1]
Neoplasm DISZKGEW Limited Biomarker [5]
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⏷ Show the Full List of 10 Disease(s)
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
This DOT Affected the Drug Response of 1 Drug(s)
Drug Name Drug ID Highest Status Interaction REF
Mitoxantrone DMM39BF Approved TBC1 domain family member 8 (TBC1D8) affects the response to substance of Mitoxantrone. [23]
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20 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 TBC1 domain family member 8 (TBC1D8). [6]
Ciclosporin DMAZJFX Approved Ciclosporin increases the expression of TBC1 domain family member 8 (TBC1D8). [7]
Acetaminophen DMUIE76 Approved Acetaminophen increases the expression of TBC1 domain family member 8 (TBC1D8). [8]
Cupric Sulfate DMP0NFQ Approved Cupric Sulfate increases the expression of TBC1 domain family member 8 (TBC1D8). [9]
Cisplatin DMRHGI9 Approved Cisplatin increases the expression of TBC1 domain family member 8 (TBC1D8). [10]
Estradiol DMUNTE3 Approved Estradiol decreases the expression of TBC1 domain family member 8 (TBC1D8). [11]
Quercetin DM3NC4M Approved Quercetin increases the expression of TBC1 domain family member 8 (TBC1D8). [12]
Hydrogen peroxide DM1NG5W Approved Hydrogen peroxide affects the expression of TBC1 domain family member 8 (TBC1D8). [13]
Calcitriol DM8ZVJ7 Approved Calcitriol increases the expression of TBC1 domain family member 8 (TBC1D8). [14]
Testosterone DM7HUNW Approved Testosterone increases the expression of TBC1 domain family member 8 (TBC1D8). [14]
Zoledronate DMIXC7G Approved Zoledronate increases the expression of TBC1 domain family member 8 (TBC1D8). [15]
Panobinostat DM58WKG Approved Panobinostat decreases the expression of TBC1 domain family member 8 (TBC1D8). [6]
Urethane DM7NSI0 Phase 4 Urethane increases the expression of TBC1 domain family member 8 (TBC1D8). [16]
Dihydrotestosterone DM3S8XC Phase 4 Dihydrotestosterone increases the expression of TBC1 domain family member 8 (TBC1D8). [17]
SNDX-275 DMH7W9X Phase 3 SNDX-275 decreases the expression of TBC1 domain family member 8 (TBC1D8). [6]
Curcumin DMQPH29 Phase 3 Curcumin increases the expression of TBC1 domain family member 8 (TBC1D8). [18]
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene decreases the expression of TBC1 domain family member 8 (TBC1D8). [19]
(+)-JQ1 DM1CZSJ Phase 1 (+)-JQ1 increases the expression of TBC1 domain family member 8 (TBC1D8). [20]
Trichostatin A DM9C8NX Investigative Trichostatin A decreases the expression of TBC1 domain family member 8 (TBC1D8). [6]
Lithium chloride DMHYLQ2 Investigative Lithium chloride decreases the expression of TBC1 domain family member 8 (TBC1D8). [22]
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⏷ Show the Full List of 20 Drug(s)
1 Drug(s) Affected the Post-Translational Modifications of This DOT
Drug Name Drug ID Highest Status Interaction REF
PMID28870136-Compound-52 DMFDERP Patented PMID28870136-Compound-52 increases the phosphorylation of TBC1 domain family member 8 (TBC1D8). [21]
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References

1 Adenoviral gene therapy for renal cancer requires retargeting to alternative cellular receptors.Cancer Res. 2002 Aug 1;62(15):4273-81.
2 CD46 represents a target for adenoviral gene therapy of malignant glioma.Hum Gene Ther. 2006 May;17(5):556-64. doi: 10.1089/hum.2006.17.556.
3 TBC1D8 Amplification Drives Tumorigenesis through Metabolism Reprogramming in Ovarian Cancer.Theranostics. 2019 Jan 24;9(3):676-690. doi: 10.7150/thno.30224. eCollection 2019.
4 An integration of genome-wide association study and gene expression profiling to prioritize the discovery of novel susceptibility Loci for osteoporosis-related traits.PLoS Genet. 2010 Jun 10;6(6):e1000977. doi: 10.1371/journal.pgen.1000977.
5 Comparison of two cancer vaccines targeting tyrosinase: plasmid DNA and recombinant alphavirus replicon particles.Clin Cancer Res. 2005 Nov 15;11(22):8114-21. doi: 10.1158/1078-0432.CCR-05-1410.
6 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.
7 Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
8 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.
9 Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
10 Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
11 Epidermal growth factor receptor signalling in human breast cancer cells operates parallel to estrogen receptor alpha signalling and results in tamoxifen insensitive proliferation. BMC Cancer. 2014 Apr 23;14:283.
12 Comparison of phenotypic and transcriptomic effects of false-positive genotoxins, true genotoxins and non-genotoxins using HepG2 cells. Mutagenesis. 2011 Sep;26(5):593-604.
13 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.
14 Effects of 1alpha,25 dihydroxyvitamin D3 and testosterone on miRNA and mRNA expression in LNCaP cells. Mol Cancer. 2011 May 18;10:58.
15 Interleukin-19 as a translational indicator of renal injury. Arch Toxicol. 2015 Jan;89(1):101-6.
16 Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
17 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.
18 Curcumin downregulates the inflammatory cytokines CXCL1 and -2 in breast cancer cells via NFkappaB. Carcinogenesis. 2008 Apr;29(4):779-89.
19 New insights into BaP-induced toxicity: role of major metabolites in transcriptomics and contribution to hepatocarcinogenesis. Arch Toxicol. 2016 Jun;90(6):1449-58.
20 Inhibition of BRD4 attenuates tumor cell self-renewal and suppresses stem cell signaling in MYC driven medulloblastoma. Oncotarget. 2014 May 15;5(9):2355-71.
21 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.
22 Early gene response in lithium chloride induced apoptosis. Apoptosis. 2005 Jan;10(1):75-90. doi: 10.1007/s10495-005-6063-x.
23 Gene expression profiling of 30 cancer cell lines predicts resistance towards 11 anticancer drugs at clinically achieved concentrations. Int J Cancer. 2006 Apr 1;118(7):1699-712. doi: 10.1002/ijc.21570.